Serum VEGF-A levels on admission in COVID-19 patients correlate with SP-D and neutrophils, reflecting disease severity: A prospective study.

BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant global morbidity and mortality. This study aimed to investigate the clinical significance of serum vascular endothelial growth factor A (VEGF-A) in COVID-19 patients and its association with disease severity and pulmonary injury. METHODS: We prospectively collected data from 71 hospitalized COVID-19 patients between June 2020 and January 2021. Patients were classified as either mild or severe based on their oxygen requirements during hospitalization. Serum VEGF-A levels were measured using an ELISA kit. RESULTS: In comparison to mild cases, significantly elevated serum VEGF-A levels were observed in severe COVID-19 patients. Furthermore, VEGF-A levels exhibited a positive correlation with white blood cell count, neutrophil count, and lymphocyte count. Notably, serum surfactant protein-D (SP-D), an indicator of alveolar epithelial cell damage, was significantly higher in patients with elevated VEGF-A levels. CONCLUSION: These results suggest that elevated serum VEGF-A levels could serve as a prognostic biomarker for COVID-19 as it is indicative of alveolar epithelial cell injury caused by SARS-CoV-2 infection. Additionally, we observed a correlation between VEGF-A and neutrophil activation, which plays a role in the immune response during endothelial cell injury, indicating a potential involvement of angiogenesis in disease progression. Further research is needed to elucidate the underlying mechanisms of VEGF-A elevation in COVID-19.

Effects of Aliskiren Monotherapy versus Amlodipine Monotherapy in Hypertensive Patients with Obesity or Type 2 Diabetes Mellitus.

INTRODUCTION: Renin-angiotensin system inhibitors have been reported to exert protective effects against organ damage and failure; however, the impact of the direct renin inhibitor as monotherapy has not been assessed. Here, we investigated the effects of 24-week monotherapy with aliskiren compared to amlodipine in hypertensive patients with type 2 diabetes or obesity. METHODS: In this randomized intervention study, 62 adult hypertensive patients with visceral obesity (defined as a body mass index [BMI] greater than 25 kg/m2 and a visceral adipose tissue area [VFA] greater than 100 cm2) or type 2 diabetes mellitus (age 57 ± 13, 65% men, BMI 28.8 ± 4.8 kg/m2, VFA 134.8 ± 47.0 cm2, blood pressure 141 ± 16/86 ± 13 mm Hg) were randomized to receive 24-week treatment with aliskiren (max. 300 mg) or amlodipine (max. 10 mg). The primary outcome was the change in VFA at 24 weeks post-treatment. RESULTS: Change in VFA did not differ significantly from baseline in either group. Systolic blood pressure significantly decreased at 12 weeks (-10 mm Hg, p = 0.001) and 24 weeks (-10 mm Hg, p = 0.001) in the amlodipine group and at 24 weeks (-11 mm Hg, p = 0.001) in the aliskiren group. Diastolic blood pressure significantly decreased at 24 weeks (-6 mm Hg, p = 0.009) only in the amlodipine group. Although the estimated glomerular filtration rates did not significantly change in either group, the logarithm of urinary albumin excretion significantly decreased at 24 weeks only in the aliskiren group (-0.60, p < 0.001). The 24-week changes in the urinary albumin excretion significantly correlated with the changes in the plasma renin activity in the aliskiren group (r = 0.51, p = 0.008). CONCLUSION: Aliskiren monotherapy did not show any superiority to amlodipine monotherapy on VFA, estimated glomerular filtration rates, or urinary albumin excretion in obese or type 2 diabetic hypertensive patients.

Clinical features and difficulty in diagnosis of Langerhans cell histiocytosis in the hypothalamic-pituitary region.

Langerhans cell histiocytosis (LCH) is a multi-organ disorder that rarely involves the hypothalamic-pituitary region (HPR). HPR-LCH presents with severe progressive pituitary dysfunction and its prognosis is poor. The definitive diagnosis of LCH is considerably difficult and complicated owing to the occurrence of several diseases with similar manifestations in the HPR and its location in the deepest portion of the anterior skull base, in close proximity to important normal structures, severely limiting the size of the biopsy specimen. Chemotherapy is the established treatment modality for LCH; hence, timely and accurate diagnosis of LCH is essential for early therapeutic intervention. We retrospectively reviewed clinical features and biopsy procedures in four patients with HPR-LCH (all female, 28-44 years old) from 2009 to 2020. Maximum diameter of supra-sellar lesions was 23-35 mm and 2 cases had skip lesions. All patients demonstrated central diabetes insipidus, hyper-prolactinemia, and severe anterior pituitary dysfunction. Two of the patients had progressive disease. Furthermore, four patients presented body weight gain, two visual disturbance, and two impaired consciousness. The duration from onset to diagnosis of LCH was 3 to 10 (average 7.25) years. In total, eight operations were performed until final diagnosis. The percentage of correct diagnosis by biopsy was 50% (4/8). Clinical features of HPR-LCH are very similar to those of other HPR diseases, and their symptoms are progressive and irreversible. Clinicians should consider repeated biopsy with a more aggressive approach if the lesion is refractory to steroid therapy, in order to ensure accurate diagnosis and appropriate treatment.

Estimation of the Risk of Postoperative Hypertension Following Minor to Moderate Surgery Using an Echocardiogram and Biomarkers.

This study aimed to determine independent factors for developing postoperative hypertension using 4 biomarkers in patients receiving oral and maxillofacial surgery under general anesthesia. Brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity myocardial troponin T (hs-TnT), and high-sensitivity myocardial troponin I (hs-TnI) were measured and preoperative echocardiograms were examined. Episodes of systolic blood pressure (SBP) ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg within 1 week after surgery were considered postoperative hypertension. We analyzed 213 (130 men; 83 women) patients, who were divided into a postoperative hypertension group (HT group, n = 32) and a normal group (N group, n = 181). The HT group showed a higher LVMI (113.5 versus 100.1), higher E/e' of the lateral wall (9.1 versus 7.7), and higher BNP (39.2 versus 22.9 pg/mL), NT-proBNP (400.1 versus 143.9 pg/mL), and hs-TnT (15.6 versus 10.3 ng/L) concentrations compared to the N group. NT-proBNP and hs-TnT concentrations positively associated with E/e', but BNP and hs-TnI did not. NT-proBNP (AUC = 0.64, cutoff value: 117.0 pg/mL) and hs-TnT (AUC = 0.61, cutoff value: 11.0 ng/L) concentrations were effective for discriminating E/e' ≥ 12. Multivariate logistic regression analyses showed that risk factors responsible for developing postoperative hypertension were NT-proBNP and hs-TnT using biomarkers and E/e' as independent variables, and NT-proBNP and SBP at admission using biomarkers and SBP at admission as independent variables. These findings suggest that NT-proBNP and hs-TnT concentrations, and SBP at admission, are useful to predict postoperative hypertension after minor to moderate surgery, and that left ventricular filling pressure is a primary factor associated with postoperative hypertension.

Sympathetic Nerve Activity During Tooth Extraction in Women Is Related to Dental Anxiety Immediately After Surgery.

PURPOSE: This study assessed the relationship between changes in autonomic nervous system activity during impacted mandibular third molar extraction and a patient's postoperative psychological status, with the overarching aim of informing the development of interventions to reduce dental phobia and anxiety. We hypothesized that changes in autonomic nervous system activity during tooth extraction are related to postoperative psychology. METHODS: In our prospective cohort study, heart rate variability, heart rate (HR), and systolic blood pressure (SBP) were recorded during impacted mandibular third molar extraction. Heart rate variability values were dichotomized as either low frequency (LF 0.04-0.15 Hz) or high frequency (HF >0.15 Hz). The relative ratios (intraoperative vs baseline) of LF/HF, HF, HR, and SBP were divided into high and low groups based on their median values; the State Anxiety Inventory (STAI-S) results were compared between the groups with high and low relative ratios. RESULTS: Data of 34 female patients (age, 28.23 ± 1.05 years) were analyzed. Postoperative STAI-S values were significantly lower than preoperative values. Patients in the high LF/HF group had a significantly lower change in STAI-S values than those in the low LF/HF group (P < .05). There were no significant differences in the change in STAI-S values between the groups with high and low HF, HR, or SBP. CONCLUSIONS: Patients with low sympathetic nervous system activity had lower anxiety; the LF/HF index was the most sensitive indicator for changes in stress. Additional studies are required to develop optimal interventions for reducing sympathetic nerve activity in patients with dental phobia.

Adrenal cortex hypoxia modulates aldosterone production in heart failure.

Plasma aldosterone concentration increases in proportion to the severity of heart failure, even during treatment with renin-angiotensin system inhibitors. This study investigated alternative regulatory mechanisms of aldosterone production that are significant in heart failure. Dahl salt-sensitive rats on a high-salt diet, a rat model of heart failure with cardio-renal syndrome, had high plasma aldosterone levels and elevated ß3-adrenergic receptor expression in hypoxic zona glomerulosa cells. In H295R cells (a human adrenocortical cell line), hypoxia-induced ß3-adrenergic receptor expression. Hypoxia-mediated ß3-adrenergic receptor expression augmented aldosterone production by facilitating hydrolysis of lipid droplets though ERK-mediated phosphorylation of hormone-sensitive lipase, also known as cholesteryl ester hydrolase. Hypoxia also accelerated the synthesis of cholesterol esters by acyl-CoA:cholesterol acyltransferase, thereby increasing the cholesterol ester content in lipid droplets. Thus, hypoxia enhanced aldosterone production by zona glomerulosa cells via promotion of the accumulation and hydrolysis of cholesterol ester in lipid droplets. In conclusion, hypoxic zona glomerulosa cells with heart failure show enhanced aldosterone production via increased catecholamine responsiveness and activation of cholesterol trafficking, irrespective of the renin-angiotensin system.

The State Anxiety Inventory Is Useful for Predicting the Autonomic Nervous System State of Patients Before the Extraction of an Impacted Mandibular Third Molar.

PURPOSE: Dental anxiety about extraction of impacted mandibular third molars changes the activity of the autonomic nervous system. Thus, to provide safe dental treatment, it is important that a surgeon be aware of a patient's pretreatment anxiety and autonomic nervous system state. Therefore, we analyzed how a scheduled treatment to extract mandibular third molars affects the pretreatment electroencephalogram (EEG), autonomic nervous system, and psychological state of patients. We compared their findings with those of volunteers not scheduled to undergo dental treatment. PATIENTS AND METHODS: The study enrolled 30 patients who were scheduled to undergo impacted mandibular third molar extraction (ie, pretreatment group) and 30 volunteers who were not (ie, control group). Heart rate variability and an EEG were recorded during the experiment. The State Anxiety Inventory-State Anxiety scale (STAI-S) scores were recorded before the procedure. For the statistical analysis, P < .05 was deemed statistically significant. RESULTS: High-frequency (HF) variability was significantly decreased and the STAI-S score was significantly increased in the pretreatment group compared with the control group (P < .01 for both). The low frequency (LF)/HF ratio and alpha-wave activity showed a significant negative correlation on both sides in the control group (P < .01); however, no correlation existed in the pretreatment group. The LF/HF ratio and STAI-S score showed a significant positive correlation in the pretreatment group (P < .05); however, no correlation existed in the control group. CONCLUSIONS: Predicting a patient's autonomic nervous system state before dental treatment based on the EEG was difficult. The STAI-S psychological test was a useful method.

Difference in the Effects of Lidocaine With Epinephrine and Prilocaine With Felypressin on the Autonomic Nervous System During Extraction of the Impacted Mandibular Third Molar: A Randomized Controlled Trial.

PURPOSE: Complications during local anesthesia include increased blood pressure and vasovagal reflex, which are caused by changes in the autonomic nervous system. The commonly used local anesthetic preparations are lidocaine to which the vasoconstrictor epinephrine is added (lidocaine-epinephrine) and prilocaine to which the vasoconstrictor felypressin is added (prilocaine-felypressin); however, their effects during dental treatment are unclear. We examined the effects of these 2 different local anesthetic preparations on the autonomic nervous system and circulation during extraction of the impacted mandibular third molar. MATERIALS AND METHODS: In this randomized controlled trial, 40 female patients scheduled for extraction of an impacted mandibular third molar were randomized to the lidocaine-epinephrine group or prilocaine-felypressin group. Heart rate variability, heart rate, and systolic blood pressure were recorded during the experiment. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: The low frequency-high frequency ratio was significantly increased in the prilocaine-felypressin group during extraction compared with that in the lidocaine-epinephrine group (P < .05). In the lidocaine-epinephrine group, a significant decrease in the high-frequency component was observed during bone removal and extraction compared with that at rest (P < .05). In both groups, a significant increase in systolic blood pressure was observed during local anesthesia, incision and reflection of the flap, bone removal, separation of the tooth crown, extraction, and suturing compared with that at rest (P < .01). CONCLUSIONS: This study is the first to investigate the differences in the influence of 2 different local anesthetic preparations on the autonomic nervous system during extraction of the mandibular third molar. Changes in circulatory dynamics during tooth extraction with the 2 different local anesthetic preparations were the result of a decrease in parasympathetic nervous activity with lidocaine-epinephrine and an increase in sympathetic nervous activity with prilocaine-felypressin.

Sirt1 counteracts decrease in membrane phospholipid unsaturation and diastolic dysfunction during saturated fatty acid overload.

BACKGROUND: The fatty acid (FA) composition of membrane phospholipid reflects at least in part dietary fat composition. Saturated FA (SFA) suppress Sirt1 activity, while monounsaturated FA (MUFA) counteract this effect. OBJECTIVE: We explored a role of Sirt1 in homeostatic control of the fatty acid composition of membrane phospholipid in the presence of SFA overload. METHODS AND RESULTS: Sirt1 deficiency in cardiomyocytes decreased the expression levels of liver X receptor (LXR)-target genes, particularly stearoyl-CoA desaturase-1 (Scd1), a rate-limiting enzyme in the cellular synthesis of MUFA from SFA, increased membrane SFA/MUFA ratio, and worsened left ventricular (LV) diastolic function in mice fed an SFA-rich high fat diet. In cultured cardiomyocytes, Sirt1 knockdown (KD) exacerbated the palmitate overload-induced increase in membrane SFA/MUFA ratio, which was associated with decrease in the expression of LXR-target genes, including Scd1. Forced overexpression of Scd1 in palmitate-overloaded Sirt1KD cardiomyocytes lowered the SFA/MUFA ratio. Nicotinamide mononucleotide (NMN) increased Sirt1 activity and Scd1 expression, thereby lowering membrane SFA/MUFA ratio in palmitate-overloaded cardiomyocytes. These effects of NMN were not observed for Scd1KD cardiomyocytes. LXRα/ßKD exacerbated palmitate overload-induced increase in membrane SFA/MUFA ratio, while LXR agonist T0901317 alleviated it. NMN failed to rescue Scd1 protein expression and membrane SFA/MUFA ratio in palmitate-overloaded LXRα/ßKD cardiomyocytes. The administration of NMN or T0901317 showed a dramatic reversal in membrane SFA/MUFA ratio and LV diastolic function in SFA-rich HFD-fed mice. CONCLUSION: Cardiac Sirt1 counteracted SFA overload-induced decrease in membrane phospholipid unsaturation and diastolic dysfunction via regulating LXR-mediated transcription of the Scd1 gene.

The Effects of Music Listening During Extraction of the Impacted Mandibular Third Molar on the Autonomic Nervous System and Psychological State.

PURPOSE: Pain, anxiety, and nervousness related to dental procedures can cause acute changes in the autonomic nervous system. Music is widely accepted as a relaxation method during dental treatment; however, its effects during dental treatment are unclear. The authors explored the effects of listening to music during extraction of the impacted mandibular third molar on the autonomic nervous system and the psychological state and hypothesized that listening to music would suppress sympathetic nervous activity and decrease anxiety. MATERIALS AND METHODS: In this prospective study, 40 patients scheduled for extraction of an impacted mandibular third molar were randomized into 2 groups: extraction without music (control group) and extraction while listening to music (music group). Heart rate variability was recorded during the experiment, and Modified Dental Anxiety Scale and State-Trait Anxiety Inventory (STAI) scores were recorded before and after the procedure. Descriptive and bivariate statistics were computed and the P value was set at .05. RESULTS: An increased low-to-high frequency ratio was observed in the control group during incision and flap reflection, bone removal, and separation of the tooth crown; the ratio was significantly decreased in the music group during these time points (P < .05). Compared with the control group, the music group had a significantly greater decrease in postoperative STAI State Anxiety scores from preoperative levels (P < .05). CONCLUSIONS: This study suggested that listening to music while undergoing extraction of the impacted mandibular third molar suppresses activity of the sympathetic nerves during incision, flap reflection, bone removal, and separation of the tooth crown and relieves anxiety after treatment. Future studies will focus on the mechanisms involved and methods to prevent the onset of systemic incidents.

Spatial transmission of H5N6 highly pathogenic avian influenza viruses among wild birds in Ibaraki Prefecture, Japan, 2016-2017.

From 29 November 2016 to 24 January 2017, sixty-three cases of H5N6 highly pathogenic avian influenza virus (HPAIV) infections were detected in wild birds in Ibaraki Prefecture, Japan. Here, we analyzed the genetic, temporal, and geographic correlations of these 63 HPAIVs to elucidate their dissemination throughout the prefecture. Full-genome sequence analysis of the Ibaraki isolates showed that 7 segments (PB2, PB1, PA, HA, NP, NA, NS) were derived from G1.1.9 strains while the M segment was from G1.1 strains; both groups of strains circulated in south China. Pathological studies revealed severe systemic infection in dead swans (the majority of dead birds and the only species necropsied), thus indicating high susceptibility to H5N6 HPAIVs. Coalescent phylogenetic analysis using the 7 G1.1.9-derived segments enabled detailed analysis of the short-term evolution of these highly homologous HPAIVs. This analysis revealed that the H5N6 HPAIVs isolated from wild birds in Ibaraki Prefecture were divided into 7 groups. Spatial analysis demonstrated that most of the cases concentrated around Senba Lake originated from a single source, and progeny viruses were transmitted to other locations after the infection expanded in mute swans. In contrast, within just a 5-km radius of the area in which cases were concentrated, three different intrusions of H5N6 HPAIVs were evident. Multi-segment analysis of short-term evolution showed that not only was the invading virus spread throughout Ibaraki Prefecture but also that, despite the small size of this region, multiple invasions had occurred during winter 2016-2017.

Predictive Factors of Postoperative Blood Pressure Abnormalities Following a Minor-to-Moderate Surgery.

Myocardial ischemic events after non-cardiac surgery is still a serious problem, especially in older, high-risk patients. However, the prevalence and risk factors of blood pressure (BP) abnormalities, which may possibly lead to myocardial ischemic attack, have not been reported. Our aim is to elucidate predictive factors of postoperative BP abnormalities following a minor-to-moderate surgery, employing preoperative left ventricular diastolic function. Patients who underwent cardiac echocardiogram examination and received oral and maxillofacial surgery under general anesthesia were enrolled. The echocardiographic parameters of diastolic function were compared between patients who had postoperative BP abnormalities (hypertension-systolic blood pressure [SBP] ≥ 170 mmHg-or hypotension-SBP < 80 mmHg-episode) that required therapeutic interventions until 7 days after surgery and those who had no BP abnormalities. Of the 173 patients analyzed, 25 (14.4%) had BP abnormalities. BP abnormalities patients were older, having a larger proportion of diabetes mellitus, lower E/A ratio and e', and larger E/e' and left atrial dimension than those without BP abnormalities. Subanalyses revealed that the independent risk factors responsible for hypertension episodes (14 patients) were the mean e' (odd ratio [OR]: 0.434; 95% confidence interval [CI]: 0.229-0.824), diabetes mellitus (OR: 5.018; 95% CI: 1.030-24.436), SBP at hospitalization (OR: 1.099; 95% CI: 1.036-1.165), and operation time (hour; OR: 1.326; 95%CI: 1.109-1.586), while hypotension episodes (11 patients) were associated solely with operation time (OR: 1.206; 95% CI: 1.046-1.391). In conclusion, left ventricular diastolic dysfunction, increased insulin resistance, boosted SBP at hospitalization, and prolonged operation should be taken into consideration as risk factors of postoperative BP abnormalities, especially hypertension, following minor-to-moderate surgery.

Recovery of Endothelial Function after Minor-to-Moderate Surgery Is Impaired by Diabetes Mellitus, Obesity, Hyperuricemia and Sevoflurane-Based Anesthesia.

Endothelial dysfunction is observed in several cardiovascular diseases, where endothelium-dependent vasodilation is impaired by oxidative stress. However, the time course of endothelial function during the perioperative period of a minor-to-moderate surgery, and the effects of atherosclerotic risk factors and employed general anesthetics on recovery of endothelial function, are unknown. Endothelial function of 30 patients was evaluated as the reactive hyperemia index (RHI) of reactive hyperemia peripheral arterial tonometry. RHI was measured on day before surgery (control), immediately after surgery (Day 0), day after surgery (Day 1), and day 4 after surgery (Day 4) in patients with no functional limitations who were scheduled for oral and maxillofacial surgery of around 3 hours. Sevoflurane- or propofol-based anesthesia supplemented with an opioid analgesic remifentanil was employed. The control RHI was 2.26 ± 0.64. The RHI significantly decreased to the lowest level on Day 0 (1.52 ± 0.28), recovered on Day 1 (2.07 ± 0.58), and improved further on Day 4 (2.55 ± 0.83). Multiple linear regression analysis revealed that recovery of the RHI from Day 0 to Day 4 was impaired by diabetes mellitus (P = 0.0313), obesity (BMI ≥ 25; P = 0.0166), hyperuricemia (uric acid ≥ 6.0 mg/dL; P = 0.0416) and sevoflurane-based anesthesia (P = 0.0308). These findings suggest that endothelial function as evaluated by the RHI is severely suppressed on the day of a minor-to-moderate surgery, and that it improves until the 4th postoperative day on average. Recovery of endothelial function is impaired by diabetes mellitus, obesity, hyperuricemia, and sevoflurane-based anesthesia.

A Label-Free Fluorescent Array Sensor Utilizing Liposome Encapsulating Calcein for Discriminating Target Proteins by Principal Component Analysis.

A new fluorescent arrayed biosensor has been developed to discriminate species and concentrations of target proteins by using plural different phospholipid liposome species encapsulating fluorescent molecules, utilizing differences in permeation of the fluorescent molecules through the membrane to modulate liposome-target protein interactions. This approach proposes a basically new label-free fluorescent sensor, compared with the common technique of developed fluorescent array sensors with labeling. We have confirmed a high output intensity of fluorescence emission related to characteristics of the fluorescent molecules dependent on their concentrations when they leak from inside the liposomes through the perturbed lipid membrane. After taking an array image of the fluorescence emission from the sensor using a CMOS imager, the output intensities of the fluorescence were analyzed by a principal component analysis (PCA) statistical method. It is found from PCA plots that different protein species with several concentrations were successfully discriminated by using the different lipid membranes with high cumulative contribution ratio. We also confirmed that the accuracy of the discrimination by the array sensor with a single shot is higher than that of a single sensor with multiple shots.

Reconsideration of Surgical Indication for Prolactin-producing Pituitary Tumor Focusing on Visual Impairment.

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

Molecular evolution of the oxytocin-oxytocin receptor system in eutherians.

Oxytocin (OXT) is a nine-amino-acid peptide hormone that is mainly released at the times of uterine contractions during parturition and milk ejection during lactation, whereas a similar peptide hormone, arginine vasopressin, primarily exerts direct antidiuretic action on the kidney and causes vasoconstriction of the peripheral vessels. The genes coding for these peptides are tandemly located on the same chromosome. A tandem duplication occurring in the common ancestor of jawed vertebrates has been proposed as responsible. In contrast to the two peptide hormones, only one oxytocin receptor (OXTR) but three arginine vasopressin receptors (AVPR1A, AVPR1B, and AVPR2) are known; these receptors probably arose from two rounds of genome duplication in the common ancestor of vertebrates. In this study, we addressed the molecular evolution of the OXT-OXTR system in eutherians. Our analyses suggest that an amino acid change from isoleucine to lysine on the eighth site (I8L) of the peptide, which corresponded to a change from mesotocin to OXT, had occurred during the common ancestral lineage of eutherians. At around the same time that the emergence of OXT occurred, functional constraints on the OXT receptor (pre-OXTR) might have relaxed, and a series of nonsynonymous substitutions might have accumulated. Only a few of these nonsynonymous substitutions might have contributed to reestablishing the molecular relationship between the OXT ligand and its receptor, after which functional constraints on the OXTR were reinstated. Since the OXT-OXTR system plays an important role in eutherians, the evolution of the OXT-OXTR system was probably an essential component of the genesis of the eutherian signature.

Evaluation of Eruption of Permanent Teeth in Beagle Dog Extraction Sites Filled with Carbonate Apatite.

Autologous bone grafting is the primary method for treating alveolar clefts. However, bone grafting materials are desired as alternatives to autogenous bone to reduce surgical invasiveness. Here, we present an animal study evaluating the effect of carbonate apatite (CA) on the spontaneous eruption of permanent teeth. The bone grafting materials included CA, natural bovine bone (BB), and hydroxyapatite (HA). In 15 8-week-old male beagle dogs, the left mandibular deciduous premolars (DP) two and three were extracted and subsequently filled with CA, BB, and HA. The animals were euthanized after a predetermined number of days, and samples were collected for microcomputed tomography and histological evaluation. Spontaneous eruption of the succeeding permanent teeth (P3 and P4) was observed in the CA group at 14 weeks. Delayed eruption of the succeeding permanent teeth was observed in the BB and HA groups. CA could serve as a viable alternative to autogenous bone for treating alveolar clefts.

Effect of GH Deficiency Caused by Nonfunctioning Pituitary Masses on Serum C-reactive Protein Levels.

Context: GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. Objective: We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. Methods: We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Results: Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (ß = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [ß] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (ß = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters. Conclusion: The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

A Case of a Pregnant Woman With Primary Aldosteronism and Superimposed Preeclampsia Treated With Esaxerenone.

During pregnancy, there is no established treatment for idiopathic hyperaldosteronism (IHA), the most common form of primary aldosteronism due to bilateral adrenal hyperplasia. Here, we report the case of a pregnant patient with IHA who was successfully treated with esaxerenone, a nonsteroidal mineralocorticoid receptor (MR) antagonist. A 39-year-old woman was diagnosed with IHA and commenced on nifedipine 20 mg daily because she desired to be pregnant. After 1 year, she became pregnant. Her blood pressure was well controlled until 34 weeks of gestation when her home blood pressure became elevated up to 140/90 mmHg. Although the dose of nifedipine was increased to 80 mg daily, her blood pressure increased to 151/97 mmHg, and urinary test showed proteinuria of 2+ in 35 weeks of gestation. She was diagnosed with superimposed preeclampsia (SPE) and additionally treated with esaxerenone. Her blood pressure decreased to 120-140/98-100 mmHg and the proteinuria improved to ±. A successful cesarean section at 37 weeks resulted in the delivery of a healthy baby boy. Her blood pressure was well controlled although esaxerenone was discontinued 2 weeks after the delivery. This is the first case of a pregnant woman who was safely treated with esaxerenone despite being a female at advanced maternal age who had been diagnosed with IHA and developed SPE. Further studies are needed to investigate the efficacy and safety of nonsteroidal selective MR antagonist in similar pregnant patients with IHA to establish better treatment strategy for these patients.

Comparison of the usefulness of the cardio-ankle vascular index and augmentation index as an index of arteriosclerosis in patients with essential hypertension.

Arteriosclerosis leads to various serious diseases that substantially reduce the quality of life. When treating hypertension, it is important to evaluate the degree of arteriosclerosis. In recent years, the cardio-ankle vascular index and augmentation index have been frequently used as indicators of arterial wall sclerosis. However, the superiority of either the cardio-ankle vascular index or the augmentation index as an index of arteriosclerosis remains unclear. Therefore, the present study compared the usefulness of these two indices as an index of arteriosclerosis. Associations between the cardio-ankle vascular index or augmentation index and risk factors for arteriosclerosis and other indices of arteriosclerosis in 535 consecutive patients with essential hypertension were evaluated. The cardio-ankle vascular index was significantly correlated with age, hemoglobin A1c, brain natriuretic peptide, and estimated glomerular filtration rate. In contrast, the augmentation index showed significant correlations only with age, brain natriuretic peptide, and estimated glomerular filtration rate. In addition, these correlations with the augmentation index were generally weaker than those with the cardio-ankle vascular index. The cardio-ankle vascular index, but not the augmentation index, was significantly correlated with flow-mediated dilation, an index of vascular endothelial function, and carotid intima-media thickness, an index of carotid atherosclerosis. Similar results were observed in subgroups stratified by sex and age. These data indicate that the cardio-ankle vascular index is more closely associated with risk factors for arteriosclerosis and other indices of arteriosclerosis than the augmentation index, suggesting that the cardio-ankle vascular index may be superior to the augmentation index as an index of arteriosclerosis.