Assessment of left ventricular geometry in normotensive type II diabetic patients.

Background: Abnormalities of glucose metabolism are associated with abnormal left ventricular geometry (LV) independent of atherosclerosis. Abnormal LV geometry, a predictor of premature cardiovascular events, indicates presence of subclinical target organ damages. Screening for abnormal LV geometry in diseases of abnormal glucose metabolism is desirable as part of their management protocol. Aim: To assess the left ventricular geometry in normotensive type II diabetic patients. Cross-sectional, descriptive, hospital-based study. One hundred normotensive type II diabetic patients drawn from the Endocrinology and Family Medicine Clinics of a tertiary hospital were age- and gender-matched with 100 apparently healthy controls. Participants meeting the criteria and informed consent proceeded for clinical evaluation, biochemical assessment, electrocardiography, and echocardiography using the American Society of Echocardiography guideline. Materials and Methods: Data were analyzed using the Statistical Package for Social Sciences [SPSS] version 25.0 (Chicago Illinois, USA). Results: Mean age of study and control groups was (55.56 ± 9.89 versus 55.47 ± 10.7) years (χ2 = 0.062, P = 0.951). The mean duration of diabetes illness was 6.57 ± 6.26 years. Prevalence of abnormal LV geometry was 51% (study) versus 18% (control) FT, P < 0.001). Concentric remodeling was the predominant geometry in 36% of study versus 11% of controls, followed by eccentric hypertrophy in 11% (study) versus 4% (control) and concentric hypertrophy in 4% (study) versus 3% (control). Geometry was normal in 49% of study against 82% in the controls (FT, P < 0.001). Significant association existed between LV geometry and duration of diabetes (χ2 = 10.793, P = 0.005). Conclusion: Abnormal LV geometry is highly prevalent in normotensive diabetic patients.

The role of SMAD signaling in hypertrophic obstructive cardiomyopathy: an immunohistopathological study in pediatric and adult patients.

Hypertrophic obstructive cardiomyopathy (HOCM) can bring a high risk of sudden cardiac death in young people. It is particularly urgent to understand the development and mechanism of HOCM to prevent unsafe incidents. Here, the comparison between pediatric and adult patients with HOCM has been performed to uncover the signaling mechanism regulating pathological process through histopathological analysis and immunohistochemical analysis. We found SMAD proteins played an important role during myocardial fibrosis for HOCM patients. In patients with HOCM, Masson and HE staining showed that myocardial cells were diffusely hypertrophied with obvious disorganized myocardial fiber alignment, and myocardial tissue was more damaged and collagen fibers increased significantly, which come early in childhood. Increased expressions of SMAD2 and SMAD3 contributed to myocardial fibrosis in patients with HOCM, which happened early in childhood and continued through adulthood. In addition, decreased expression of SMAD7 was closely related to collagen deposition, which negatively expedited fibrotic responses in patients with HOCM. Our study indicated that the abnormal regulation of SMAD signaling pathway can lead to severe myocardial fibrosis in childhood and its fibrogenic effects persist into adulthood, which is a crucial factor in causing sudden cardiac death and heart failure in HOCM patients.

[Isolated IgG4 hypertrophic pachymeningitis with cranial nerve involvement].

IgG4-related (IgG4-RD) disease is a relatively newly identified, chronic autoimmune disorder that can affect any organ system. The disease is relatively rare. It has mostly systemic presentation, however it can also appear in isolated form in one single organ. In our report, we demonstrate an elderly male patient's case with IgG4-RD presented in the form of diffuse meningeal inflammation and hypertrophic pachymeningitis with one-sided cranial nerve and intraventricular involvement.

Ca2+/Calmodulin-dependent Protein Kinase II Inhibitor KN-93 Enhances Chondrogenesis of Bone Marrow Mesenchymal Stem Cells and Delays Chondrogenic Hypertrophy.

BACKGROUND/AIM: Cartilage tissue engineering has been popularly applied in the treatment of articular cartilage defect because it is more effective in generating functional engineered cartilage than traditional methods. Although the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) is well established, it is often accompanied by undesired hypertrophy. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a crucial mediator in the ion channel pathway which is known to be involved in chondrogenic hypertrophy. Therefore, this study aimed to reduce the hypertrophy of BM-MSCs by inhibiting CaMKII activation. MATERIALS AND METHODS: BM-MSCs were cultured in three-dimensional (3D) scaffold under chondrogenic induction with and without CaMKII inhibitor, KN-93. After cultivation, markers of chondrogenesis and hypertrophy were investigated. RESULTS: KN-93 at a concentration of 2.0 µM had no effect on the viability of BM-MSCs, while the activation of CaMKII was suppressed. A long period of KN-93 treatment significantly up-regulated the expression of SRY-box transcription factor 9 and aggrecan on day 28 compared to untreated BM-MSCs. Furthermore, KN-93 treatment significantly down-regulated the expression of RUNX family transcription factor 2 and collagen type X alpha 1 chain on days 21 and 28. Immunohistochemistry showed increased expression of aggrecan and type II collagen while the expression of type X collagen was reduced. CONCLUSION: A CaMKII inhibitor, KN-93 is able to enhance chondrogenesis of BM-MSCs and suppress chondrogenic hypertrophy, suggesting its potential applicability in cartilage tissue engineering.

Alterations in Amygdala/Hippocampal Volume Ratios in Children with Obstructive Sleep Apnea Syndrome Caused by Adenotonsillar Hypertrophy.

BACKGROUND Intermittent hypoxemia can cause changes in certain brain structures. However, in pediatric patients with obstructive sleep apnea (OSA) caused by adenotonsillar hypertrophy (ATH), there is only limited information on the effect of ATH-induced OSA on brain structures. This study sought to investigate alterations in amygdala and hippocampal volumes in children with OSA by ATH. MATERIAL AND METHODS Magnetic resonance imaging scans were applied in children who had ATH-induced OSA (ATH/OSA) and in healthy children. Amygdala and hippocampus volumes and adenoid sizes were measured on MRI volumetric images. The ratio of adenoid size/nasopharyngeal depth was used to describe the severity of adenoid hypertrophy. The clinical variables of the involved subjects were investigated. RESULTS One hundred ATH/OSA children and 100 healthy children without ATH/OSA participated in the study. The ATH/OSA children had higher amygdala volumes and amygdala/hippocampus volume ratios but lower hippocampus volumes than healthy controls, and the amygdala/hippocampus volume ratios were correlated with disease duration and hypoxemia conditions. However, our data showed that amygdala/hippocampus volume ratios were not correlated with the ratios of adenoid size/nasopharyngeal depth in the ATH/OSA children. In addition, the ratio of adenoid size/nasopharyngeal depths in ATH/OSA children was higher than that in healthy children in each subgroup based on the age of participants. CONCLUSIONS Compared to healthy controls, amygdala/hippocampus volume ratios are increased in children with ATH/OSA.

Rhythm and conduction complications after COVID-19 infection in physiological hypertrophy of myocardium (athlete's heart).

The term 'athletic heart syndrome' (AHS) is used to describe specific circulatory and morphological changes in individuals who participate in sports competitions. The syndrome is characterized by normal cardiac function and reversible myocardial remodelling.The incidence and severity of the post-COVID-19 cardiac pathology in active athletes are so far unclear. One of the complications involving the heart is myocarditis. We present a case of a 23-year-old rower after having a moderate COVID-19 infection. Electrocardiograms showed evidence of a shift in conduction and rhythm disturbances ranging from Group 1 (normal ECG findings) to Group 2 (abnormal ECG findings) on the background of an AHS. Echocardiography (with new methods of evaluating deformity - Global Longitudinal Strain) revealed an area with mildly reduced left ventricular deformity around the apex. To assess the subtle alterations in the myocardium, magnetic resonance imaging was used and focal myocarditis was detected. In our patient, considering the degree of severity of his COVID-19 infection - a moderate one, a decision was taken to perform a clinical and instrumental reassessment of his cardiovascular complications 6 months after the infection.This clinical case presents two substantial issues. First, is the AHS more susceptible to rhythm and conduction disturbances after a COVID-19 infection than that of a person who does not actively participate in sports? Second, what the reversibility or the definitive nature of these disturbances is, and how this impacts the prognosis associated with an active sporting activity.

Substernal multinodular goiter resulting in superior vena cava syndrome and tracheal compression.

A woman in her early 70s presented to the family medicine clinic with shortness of breath and an inability to lie flat for several months. When lying flat or on lifting her arms above her head, her face would turn bright red and she felt lightheaded. The patient also had hair loss and skin colour changes of the upper extremities. On examination, the thyroid was palpated and felt normal without enlargement or nodularity. Considering the patient's 70-90 pack-year smoking history, a malignant process of the lung causing superior vena cava syndrome was suspected. CT chest with intravenous contrast revealed a markedly enlarged thyroid with substernal extension of a multinodular goitre producing a mass effect in the upper mediastinum. Thyroid-stimulating hormone was normal. The patient had a total thyroidectomy performed by endocrine surgery. Pathology revealed multinodular hyperplasia and chronic lymphocytic thyroiditis. The patient recovered well postoperatively and her compressive symptoms resolved.

[Study on protective effects and mechanisms of total glucosides of Paeony on Graves disease in BALB/c mice].

Objective: To investigate the protective effect and its immunoregulatory mechanism of Total Glucosides of Paeony (TGP) against Graves' Disease (GD) model on BALB/c mice. Methods: Fifty female (6 weeks old, weighing 16-18 g) BALB/c mice of specific pathogen free were divided into control group according to random number table method, model group, early low-dose TGP intervention group (250 mg·kg-1·d-1), early high-dose TGP intervention group (500 mg·kg-1·d-1), and late TGP intervention group, with 10 mice in each group. Except the control group, the other 4 groups were immunized 3 times (0, 3rd, and 6th week) with recombinant adenovirus expressing the thyroid stimulating hormone receptor (TSHR) A subunit to establish the GD model. The early low-dose and high-dose intervention group were given diets containing different doses of TGP throughout the whole process, and the late intervention group was given diets containing low doses of TGP from the 1st week after the 2nd immunization (week 4). The levels of thyrotropin receptor antibody (TRAb) and total thyroxine (TT4) were detected in the tail venous blood of mice at the 4th week. At the 10th week, the serum TRAb and TT4 levels and the ratio of regulatory T cells (Treg) in each group were detected, and the pathological changes of thyroid tissue were observed. Serum helper T cell 1(Th1) and Th2 cell-related factors interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factors-α (TNF-α) were detected to investigate the protective effect of TGP on GD model in BALB/c mice and its mechanism. Results: At the 4th week, The level of TT4 [(55.07±12.89) µg/L] in early high-dose intervention group was lower than that in model group [(74.33±8.63) µg/L] (all P<0.05). The level of TT4 in early low-dose intervention group and late intervention group and model group had no statistical significance (all P>0.05). TRAb level of mice between early low-dose, early high-dose, late intervention groups and model group was no significant difference (all P>0.05). At the 10th week, TRAb [(90.00±26.89) U/L] and TT4[(32.66±8.11) µg/L] levels in the early high-dose intervention group were lower than those in the model group [(396.97±95.35) U/L, (73.70±16.33) µg/L] (all P<0.05). The TRAb and TT4 levels in the early low-dose intervention group and late intervention group were not significantly different from those in the model group (all P>0.05). The thyroid tissue of hyperthyroidism mice in the early high dose intervention group showed focal hypertrophic changes, while the thyroid tissue of other hyperthyroidism mice showed diffuse hypertrophic changes. The CD4+CD25+/CD4+Treg ratio in early high-dose intervention group was higher than that in model group at the 10th week (4 weeks after three recombinant adenovirus immunization) (P<0.05). Compared with the model group at the 10th week, the levels of IL-2, IL-12p70 and IFN-γ in the early high-dose intervention group were all decreased (all P<0.05), and the levels of IL-10 were increased (P<0.05). Conclusion: Early high-dose (500 mg·kg-1·d-1) TGP intervention group displays a protective effect against GD mice, the mechanism of which may be related to regulatory T cell function changes and Th1/Th2 cytokine balance restoration.

Efficacy of resistance training in hypoxia on muscle hypertrophy and strength development: a systematic review with meta-analysis.

A systematic review and meta-analysis was conducted to determine the effects of resistance training under hypoxic conditions (RTH) on muscle hypertrophy and strength development. Searches of PubMed-Medline, Web of Science, Sport Discus and the Cochrane Library were conducted comparing the effect of RTH versus normoxia (RTN) on muscle hypertrophy (cross sectional area (CSA), lean mass and muscle thickness) and strength development [1-repetition maximum (1RM)]. An overall meta-analysis and subanalyses of training load (low, moderate or high), inter-set rest interval (short, moderate or long) and severity of hypoxia (moderate or high) were conducted to explore the effects on RTH outcomes. Seventeen studies met inclusion criteria. The overall analyses showed similar improvements in CSA (SMD [CIs] = 0.17 [- 0.07; 0.42]) and 1RM (SMD = 0.13 [0.0; 0.27]) between RTH and RTN. Subanalyses indicated a medium effect on CSA for longer inter-set rest intervals and a small effect for moderate hypoxia and moderate loads favoring RTH. Moreover, a moderate effect for longer inter-set rest intervals and a trivial effect for severe hypoxia and moderate loads favoring RTH was found on 1RM. Evidence suggests that RTH employed with moderate loads (60-80% 1RM) and longer inter-set rest intervals (≥ 120 s) enhances muscle hypertrophy and strength compared to normoxia. The use of moderate hypoxia (14.3-16% FiO2) seems to be somewhat beneficial to hypertrophy but not strength. Further research is required with greater standardization of protocols to draw stronger conclusions on the topic.

Castleman disease: a rare case in a young woman.

Castleman disease is a rare lymphoproliferative disorder characterized by benign enlargement of lymph nodes. It is divided into unicentric disease, which involves a single enlarged lymph node, and multicentric disease, which affects multiple lymph node stations. In this report, we describe a rare case of a 28-year-old female patient with an unicentric Castleman disease. Computed tomography and magnetic resonance imaging revealed a well-circumscribed large mass in the left neck, characterized by intense homogenous enhancement and suspected for a malignant disease. The patient underwent an excisional biopsy for definitive diagnosis of unicentric Castleman disease and ruled out malignant conditions.

Pediatric sleep-disordered breathing in Shanghai: characteristics, independent risk factors and its association with malocclusion.

OBJECTIVES: This study aimed to determine the prevalence and independent risk factors of SDB, and explore its association with malocclusion among 6-11-year-old children in Shanghai, China. METHODS: A cluster sampling procedure was adopted in this cross-sectional study. Pediatric Sleep Questionnaire (PSQ) was applied to evaluate the presence of SDB. Questionnaires including PSQ, medical history, family history, and daily habits/environment were completed by parents under instruction, and oral examinations were implemented by well-trained orthodontists. Multivariable logistic regression was applied to identify independent risk factors for SDB. Chi-square tests and Spearman's Rank Correlation were used to estimate the relationship between SDB and malocclusion. RESULTS: A total of 3433 subjects (1788 males and 1645 females) were included in the study. The SDB prevalence was about 17.7%. Allergic rhinitis (OR 1.39, 95% CI 1.09-1.79), adenotonsillar hypertrophy (OR 2.39, 95% CI 1.82-3.19), paternal snoring (OR 1.97, 95% CI 1.53-2.53), and maternal snoring (OR 1.35, 95% CI 1.05-1.73) were independent risk factors for SDB. The SDB prevalence was higher in children with retrusive mandibles than in proper or excessive ones. No significant difference was observed in the correlation between SDB and lateral facial profile, mandible plane angle, constricted dental arch form, the severity of anterior overjet and overbite, degree of crowding and spacing, and the presence of crossbite and open bite. CONCLUSIONS: The prevalence of SDB in primary students in the Chinese urban population was high and highly associated with mandible retrusion. The independent risk factors included Allergic rhinitis, adenotonsillar hypertrophy, paternal snoring, and maternal snoring. More efforts should be made to enhance public education about SDB and related dental-maxillofacial abnormalities.

IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression.

IL-12α plays an important role in modulating inflammatory response, fibroblast proliferation and angiogenesis through modulating macrophage polarization or T cell function, but its effect on cardiorespiratory fitness is not clear. Here, we studied the effect of IL-12α on cardiac inflammation, hypertrophy, dysfunction, and lung remodeling in IL-12α gene knockout (KO) mice in response to chronic systolic pressure overload produced by transverse aortic constriction (TAC). Our results showed that IL-12α KO significantly ameliorated TAC-induced left ventricular (LV) failure, as evidenced by a smaller decrease of LV ejection fraction. IL-12α KO also exhibited significantly attenuated TAC-induced increase of LV weight, left atrial weight, lung weight, right ventricular weight, and the ratios of them in comparison to body weight or tibial length. In addition, IL-12α KO showed significantly attenuated TAC-induced LV leukocyte infiltration, fibrosis, cardiomyocyte hypertrophy, and lung inflammation and remodeling (such as lung fibrosis and vessel muscularization). Moreover, IL-12α KO displayed significantly attenuated TAC-induced activation of CD4+ T cells and CD8+ T cells in the lung. Furthermore, IL-12α KO showed significantly suppressed accumulation and activation of pulmonary macrophages and dendritic cells. Taken together, these findings indicate that inhibition of IL-12α is effective in attenuating systolic overload-induced cardiac inflammation, heart failure development, promoting transition from LV failure to lung remodeling and right ventricular hypertrophy.

Hypertrophic olivary degeneration associated with bilateral vocal cord adductor dystonia.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions within the dentato-rubro-olivary pathway, resulting in ocular nystagmus and palatal myoclonus (oculopalatal tremor) but not usually dystonia. Dystonia is an uncommon association, and we present the first reported association of hypertrophic olivary degeneration with bilateral vocal cord dystonia. CASE PRESENTATION: A 33 year old male presented initially with acute hydrocephalus on the background of previous ventriculoperitoneal (VP) shunting for previously treated medulloblastoma. After revision of the VP shunt, the patient developed progressive hiccups and stridor leading to respiratory failure requiring intubation. Ocular pendular nystagmus and palatal myoclonus at 3 Hz was observed. Flexible nasendoscopy (FNE) demonstrated bilateral tonic adduction of the vocal folds with 3 Hz coarse supraglottic, pharyngeal and palatal rhythmic myoclonus. MRI imaging demonstrated T2 hyperintensity within the bilateral inferior olivary nuclei consistent with stage 3 radiological HOD. CONCLUSIONS: Dystonia is a rarely reported phenomenon in HOD but is not unexpected with the inferior olivary nucleus implicated in dystonic disorders. We report the association of HOD with bilateral vocal cord adductor dystonia, a potentially life threatening condition.

Periostin splice variants affect craniofacial growth by influencing chondrocyte hypertrophy.

INTRODUCTION: Periostin, an extracellular matrix protein, plays an important role in osteogenesis and is also known to activate several signals that contribute to chondrogenesis. The absence of periostin in periostin knockout mice leads to several disorders such as craniosynostosis and periostitis. There are several splice variants with different roles in heart disease and myocardial infarction. However, little is known about each variant's role in chondrogenesis, followed by bone formation. Therefore, the aim of this study is to investigate the role of several variants in chondrogenesis differentiation and bone formation in the craniofacial region. Periostin splice variants included a full-length variant (Control), a variant lacking exon 17 (ΔEx17), a variant lacking exon 21 (ΔEx21), and another variant lacking both exon 17 and 21 ***(ΔEx17&21). MATERIALS AND METHODS: We used C56BL6/N mice (n = 6) for the wild type (Control)*** and the three variant type mice (n = 6 each) to identify the effect of each variant morphologically and histologically. Micro-computed tomography demonstrated a smaller craniofacial skeleton in ΔEx17s, ΔEx21s, and ΔEx17&21s compared to Controls, especially the mandibular bone. We, thus, focused on the mandibular condyle. RESULTS: The most distinctive histological observation was that each defected mouse appeared to have more hypertrophic chondrocytes than Controls. Real-time PCR demonstrated the differences among the group. Moreover, the lack of exon 17 or exon 21 in periostin leads to inadequate chondrocyte differentiation and presents in a diminutive craniofacial skeleton. DISCUSSION: Therefore, these findings suggested that each variant has a significant role in chondrocyte hypertrophy, leading to suppression of bone formation.

Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM. METHODS: A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve. RESULTS: Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers (P<0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (ß-coefficient, -0.031 mL/g per min [CI, -0.06 to -0.01]; P=0.013), higher ejection fraction (-0.025 mL/g per min [CI, -0.04 to -0.01]; P<0.005), and ECG maximum R-wave height (-0.023 mL/g per min [CI, -0.04 to -0.01]; P<0.005). CONCLUSIONS: Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

BACKGROUND: The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. METHODS: We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. RESULTS: We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). CONCLUSIONS: Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Integrated network pharmacology and molecular docking analyses of the mechanisms underlying the antihypertensive effects of lotusine.

Hypertension is a modifiable cardiovascular risk factor and cause of death worldwide. Lotusine, an alkaloid extracted from a plant used in traditional Chinese Medicine, has shown anti-hypertensive effects. However, its therapeutic efficacy requires further investigation. We adopted integrated network pharmacology and molecular docking approaches with the aim of investigating lotusine's antihypertensive effects and mechanisms of action in rat models. After identifying the optimal intravenous dosage, we observed the effects of lotusine administration on two-kidney, one-clip (2K1C) rats and spontaneously hypertensive rats (SHRs). Based on network pharmacology and molecular docking analyses, we measured renal sympathetic nerve activity (RSNA) to evaluate lotusine's effect. Finally, an abdominal aortic coarctation (AAC) model was established to evaluate lotusine's long-term effects. The network pharmacology analysis identified 21 intersection targets; of these, 17 were also implicated by the neuroactive live receiver interaction. Further integrated analysis showed high lotusine affinity for the cholinergic receptor nicotinic alpha 2 subunit, adrenoceptor beta 2, and adrenoceptor alpha 1B. Blood pressure of the 2K1C rats and SHRs decreased after treatment with 2.0 and 4.0 mg/kg of lotusine (P < 0.001 versus saline control). We also observed RSNA decreases consistent with the network pharmacology and molecular docking analysis results. Results from the AAC rat model indicated that myocardial hypertrophy was decreased with lotusine administration, demonstrated by echocardiography and hematoxylin and eosin and Masson staining. This study provides insights into the antihypertensive effects and underlying mechanisms of lotusine; lotusine may exert long-term protective effects against myocardial hypertrophy caused by elevated blood pressure.

Role of cord blood IGF-1 and maternal HbA1c levels to predict interventricular septal hypertrophy among infants of diabetic mothers: A case-control study.

BACKGROUND: Infants of diabetic mothers (IDMs) develop interventricular septal hypertrophy (ISH) (> 6 mm) [1]. The proportion of IDMs developing ISH varies from country to country. Maternal HbA1c and cord blood Insulin-like growth factor-1 (IGF-1) levels have been found useful to predict ISH. METHODS: This was a case-control study of term neonates of diabetic mothers (cases) and of non-diabetic mothers (controls) to evaluate echocardiographic (ECHO) differences among cases and controls and to find the correlation of interventricular septal thickness (IVS) thickness with maternal HbA1C and cord blood IGF-1 levels. RESULTS: Of 32 cases and 34 controls (mean gestational age 37.7 ± 0.9 weeks), 15 (46.8 %) cases, no control developed ISH. Septal thickness was more (6 ± 0.15 cm vs 3 ± 0.06 cm; p = 0.027) in cases than controls. Functional ECHO parameters including left ventricle ejection fraction were comparable (p = 0.9) among the two groups. Maternal HbA1C levels were higher (6.5 % ± 1.3 vs 3.6 % ± 0.7; p = 0.001) with a positive correlation with IVS (Pearson's coefficient 0.784, p < 0.001). Cord blood IGF1 levels were too higher in cases (99.1 ± 6.09 ng/ml vs 37.1 ± 2.99 ng/ml; p < 0.001) with moderate correlation with IVS thickness (Pearson's coefficient 0.402; p = 0.00). Receiver operator curve analysis showed, that at a cut-off of 72 ng/ml, cord blood IGF1 predicted ISH with 72 % sensitivity; 88 % specificity and at a cut-off of 7.35 %, maternal HbA1c predicted ISH with sensitivity; specificity of 93.8 % and 72.1 % respectively. CONCLUSION: ISH was present in 46.8 % in cases as compared to none in controls. IVS thickness correlated well with maternal HbA1C and moderately with cord blood IGF-1 levels. Functional parameters on ECHO were unaffected by maternal diabetic control. At the cut-off of maternal HbA1c of 7.35 % and cord blood IGF-1 of 72 ng /ml, babies need to be monitored clinically with ECHO to look for ISH.

Muscle group-specific skeletal muscle aging: a 5-yr longitudinal study in septuagenarians.

There is some evidence that the age-associated change in skeletal muscle mass is muscle specific, yet the number of specific muscles that have been studied to form our understanding in this area is limited. In addition, few aging investigations have examined multiple muscles in the same individuals. This longitudinal investigation compared changes in skeletal muscle size via computed tomography of the quadriceps (rectus femoris, vastus lateralis, vastus medialis, and vastus intermedius), hamstrings (biceps femoris short and long heads, semitendinosus, and semimembranosus), psoas, rectus abdominis, lateral abdominals (obliques and transversus abdominis), and paraspinal muscles (erector spinae and multifidi) of older individuals from the Health, Aging, and Body Composition (Health ABC) study at baseline and 5.0 ± 0.1 years later (n = 469, 73 ± 3 yr and 78 ± 3 yr, 49% women, 33% black). Skeletal muscle size decreased (P < 0.05) in quadriceps (-3.3%), hamstrings (-5.9%), psoas (-0.4%), and rectus abdominis (-7.0%). The hamstrings and rectus abdominis atrophied approximately twice as much as the quadriceps (P < 0.05), whereas the quadriceps atrophied substantially more than the psoas (P < 0.05). The lateral abdominals (+5.9%) and paraspinals (+4.3%) hypertrophied (P < 0.05) to a similar degree (P > 0.05) over the 5 years. These data suggest that older individuals experience skeletal muscle atrophy and hypertrophy in a muscle group-specific fashion in the eighth decade, a critical time period in the aging process. A broader understanding of muscle group-specific skeletal muscle aging is needed to better guide exercise programs and other interventions that mitigate decrements in physical function with aging.NEW & NOTEWORTHY These longitudinal analyses of six muscle groups in septuagenarians provide novel information on the muscle group-specific aging process. Although the quadriceps, hamstrings, psoas, and rectus abdominis atrophied with different magnitudes, the lateral abdominals and paraspinals hypertrophied over the 5 years. These findings contribute to a better understanding of the skeletal muscle aging process and highlight the need to complete studies in this area with a muscle-specific focus.

Automatic detection of adenoid hypertrophy on cone-beam computed tomography based on deep learning.

INTRODUCTION: This study proposed an automatic diagnosis method based on deep learning for adenoid hypertrophy detection on cone-beam computed tomography. METHODS: The hierarchical masks self-attention U-net (HMSAU-Net) for segmentation of the upper airway and the 3-dimensional (3D)-ResNet for diagnosing adenoid hypertrophy were constructed on the basis of 87 cone-beam computed tomography samples. A self-attention encoder module was added to the SAU-Net to optimize upper airway segmentation precision. The hierarchical masks were introduced to ensure that the HMSAU-Net captured sufficient local semantic information. RESULTS: We used Dice to evaluate the performance of HMSAU-Net and used diagnostic method indicators to test the performance of 3D-ResNet. The average Dice value of our proposed model was 0.960, which was superior to the 3DU-Net and SAU-Net models. In the diagnostic models, 3D-ResNet10 had an excellent ability to diagnose adenoid hypertrophy automatically with a mean accuracy of 0.912, a mean sensitivity of 0.976, a mean specificity of 0.867, a mean positive predictive value of 0.837, a mean negative predictive value of 0.981, and a F1 score of 0.901. CONCLUSIONS: The value of this diagnostic system lies in that it provides a new method for the rapid and accurate early clinical diagnosis of adenoid hypertrophy in children, allows us to look at the upper airway obstruction in three-dimensional space and relieves the work pressure of imaging doctors.