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BACKGROUND: Recent advances in fetal ultrasound imaging, especially four-dimensional (4D) spatio-temporal image correlation techniques permit detailed evaluation of the fetal venous system and its abnormalities. In this report, we present the clinical presentation, conventional/4D spatio-temporal image correlation imaging findings, pregnancy, and early postnatal outcomes in fetuses having anomalies of systemic venous return in the absence of significant intracardiac defects from two centres in southern India. OBJECTIVES: To report the clinical presentation, conventional/4D spatio-temporal image correlation imaging findings, pregnancy, and early postnatal outcomes in fetuses having anomalies of systemic venous return in the absence of significant intracardiac defects from two centres in Southern India. METHODS: Retrospective study (October 2017 to March 2022). All fetuses referred with abnormal cardiac imaging findings who were diagnosed to have anomalies of systemic venous return in the absence of significant intracardiac defects were included. Imaging techniques like 2D with color and 4D spatio-temporal image correlation fetal imaging were used to evaluate systemic venous anomalies. Systemic venous anomalies were grouped into cardinal venous anomalies and umbilico-portosystemic venous anomalies. RESULTS: Thirty-nine fetuses were included; this represented 4.4% of all cardiac anomalies diagnosed during the study period. Cardinal venous anomalies were seen in 29 fetuses (74%); the mean gestation age at diagnosis was 25.5 ± 3.4 weeks. Absent dilated coronary sinus was associated with anomalous drainage of superior caval vein through completely unroofed coronary sinus into the left atrium (n = 3) which resulted in cyanosis after birth in all infants. Among the three cases, one underwent surgery at 6 months of age due to a progressive increase in cyanosis (Spo2 78%) and others are awaiting surgery. A prenatal genetic evaluation was performed in 17 (58.6%). Cardinal venous anomalies were not associated with genetic abnormalities. Live births occurred in all fetuses with cardinal venous anomalies. Umbilico-portosystemic venous anomalies were seen in 10 (26%). The mean gestation age at diagnosis was 26.5 ± 4.5 weeks. Except in a fetus with the extrahepatic portosystemic shunt (umbilical vein to iliac vein), the genetic evaluation was normal in our cohort. Extracardiac anomalies (n = 3/10; 30%) were seen in both intra (n = 1) and extrahepatic portosystemic shunts (n = 2). CONCLUSION: Anomalies of systemic venous return in the absence of significant intracardiac, extracardiac, and genetic abnormalities carried an overall favorable prognosis in our cohort. Precise characterization of anatomic details using advanced imaging techniques helps in the understanding of this complex three-dimensional anatomy and in the prognostication of these anomalies.
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Cardiopatías Congénitas , Vena Cava Superior , Embarazo , Femenino , Humanos , Lactante , Estudios Retrospectivos , Feto/irrigación sanguínea , Cardiopatías Congénitas/diagnóstico por imagen , Diagnóstico Prenatal , Ultrasonografía PrenatalRESUMEN
TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel that is predominantly localized to the membranes of late endosomes and lysosomes (LELs). Intracellular release of Ca2+ through TRPML1 is thought to be pivotal for maintenance of intravesicular acidic pH as well as the maturation, fusion, and trafficking of LELs. Interestingly, genetic ablation of TRPML1 in mice (Mcoln1-/- ) induces a hyperdistended/hypertrophic bladder phenotype. Here, we investigated this phenomenon further by exploring an unconventional role for TRPML1 channels in the regulation of Ca2+-signaling activity and contractility in bladder and urethral smooth muscle cells (SMCs). Four-dimensional (4D) lattice light-sheet live-cell imaging showed that the majority of LELs in freshly isolated bladder SMCs were essentially immobile. Superresolution microscopy revealed distinct nanoscale colocalization of LEL-expressing TRPML1 channels with ryanodine type 2 receptors (RyR2) in bladder SMCs. Spontaneous intracellular release of Ca2+ from the sarcoplasmic reticulum (SR) through RyR2 generates localized elevations of Ca2+ ("Ca2+ sparks") that activate plasmalemmal large-conductance Ca2+-activated K+ (BK) channels, a critical negative feedback mechanism that regulates smooth muscle contractility. This mechanism was impaired in Mcoln1-/- mice, which showed diminished spontaneous Ca2+ sparks and BK channel activity in bladder and urethra SMCs. Additionally, ex vivo contractility experiments showed that loss of Ca2+ spark-BK channel signaling in Mcoln1-/- mice rendered both bladder and urethra smooth muscle hypercontractile. Voiding activity analyses revealed bladder overactivity in Mcoln1-/- mice. We conclude that TRPML1 is critically important for Ca2+ spark signaling, and thus regulation of contractility and function, in lower urinary tract SMCs.
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Canales de Calcio/metabolismo , Calcio/metabolismo , Contracción Muscular , Músculo Liso/metabolismo , Miocitos del Músculo Liso/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo , Fenómenos Fisiológicos del Sistema Urinario , Animales , Biomarcadores , Técnica del Anticuerpo Fluorescente , Expresión Génica , Espacio Intracelular/metabolismo , Masculino , Potenciales de la Membrana , Ratones , Ratones Noqueados , Contracción Muscular/genética , Transporte de Proteínas , Canales de Potencial de Receptor Transitorio/genética , Vejiga Urinaria/metabolismo , Vejiga Urinaria/fisiopatologíaRESUMEN
We report an antenatal presentation of a huge pericardial mature teratoma that was referred as congenital pulmonary airway malformation (CPAM) in the late third trimester of pregnancy. Initial ultrasound evaluation revealed a huge predominantly cystic lesion with mixed echogenicity in the left hemithorax. A provisional diagnosis of pleural tumor was considered in view of previous scans at 20â28 weeks being normal and associated pleural effusion. Magnetic resonance imaging of the fetus reported the lesion to be CPAM which was supported by postnatal computed tomographic imaging done on day 2 of life. However, intraoperatively, the lesion was found to be of pericardial origin which on subsequent histopathological examination was confirmed to be mature teratoma. We recommend considering potential differential diagnosis other than CPAM, especially when the lesion is found for the first time in the late third trimester.
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PURPOSE: Closed spina bifida (CSB) is rare in prenatal literature, and various lesions are grouped under this broad nosological entity CSB, leading to confusing and misleading prognostic conclusions. METHODS: This is a retrospective observational cohort study of prenatally detected CSB cases using two-dimensional ultrasound, complemented by three-dimensional ultrasonography and foetal MRI in indicated cases, from October 2014 to October 2021 in a tertiary-level single centre. RESULTS: The most common upper vertebral level of CSB was lumbar in 66.6% (10/15). The sub-classification of lesions based on prenatal ultrasound showed an agreement in 53% of the cases. Sixty percent had associated abnormalities identified postnatally, the most common being anorectal malformation seen in 33.3%. On postnatal follow-up, 46.6% had bowel incontinence and bladder dysfunction, and 33.3% developed lower limb deformities. CONCLUSIONS: All CSBs do not have a uniformly favourable prognosis. The prognosis of CSB depends on the pathological type, the presence of associated abnormalities and the management.
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Espina Bífida Oculta , Disrafia Espinal , Estudios de Cohortes , Consejo , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Disrafia Espinal/diagnóstico por imagen , Disrafia Espinal/cirugía , Ultrasonografía PrenatalRESUMEN
Testosterone regulates dimorphic sexual behaviors in all vertebrates. However, the molecular mechanism underlying these behaviors remains unclear. Here, we report that a newly identified rapid testosterone signaling receptor, Transient Receptor Potential Melastatin 8 (TRPM8), regulates dimorphic sexual and social behaviors in mice. We found that, along with higher steroid levels in the circulation, TRPM8-/- male mice exhibit increased mounting frequency indiscriminate of sex, delayed sexual satiety, and increased aggression compared to wild-type controls, while TRPM8-/- females display an increased olfaction-exploratory behavior. Furthermore, neuronal responses to acute testosterone application onto the amygdala were attenuated in TRPM8-/- males but remained unchanged in females. Moreover, activation of dopaminergic neurons in the ventral tegmental area following mating was impaired in TRPM8-/- males. Together, these results demonstrate that TRPM8 regulates dimorphic sexual and social behaviors, and potentially constitutes a signalosome for mediation of sex-reward mechanism in males. Thus, deficiency of TRPM8 might lead to a delayed sexual satiety phenomenon.
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Conducta Animal/fisiología , Receptores Androgénicos/metabolismo , Conducta Sexual Animal/fisiología , Transducción de Señal/fisiología , Canales Catiónicos TRPM/metabolismo , Testosterona/metabolismo , Agresión/fisiología , Animales , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/fisiología , Femenino , Masculino , Ratones , Caracteres Sexuales , Conducta Social , Área Tegmental Ventral/metabolismo , Área Tegmental Ventral/fisiologíaRESUMEN
Cenani Lenz syndrome is a rare autosomal recessive disorder associated with variable degree of limb malformations, dysmorphism, and renal agenesis. It is caused due to pathogenic variants in the LRP4 gene, which plays an important role in limb and renal development. Mutations in the APC gene have also been occasionally associated with CLS. The phenotypic spectrum ranges from mild to very severe perinatal lethal type depending on the type of variant. We report a pathogenic variant, c.2710 del T (p.Trp904GlyfsTer5) in theLRP4 gene, in a fetus with lethal Cenani Lenz syndrome with antenatal presentation of tetraphocomelia and symmetrical involvement of hands and feet.
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Anomalías Congénitas/genética , Enfermedades Renales/congénito , Riñón/anomalías , Proteínas Relacionadas con Receptor de LDL/genética , Deformidades Congénitas de las Extremidades/genética , Sindactilia/genética , Feto Abortado/patología , Proteína de la Poliposis Adenomatosa del Colon/genética , Anomalías Congénitas/mortalidad , Anomalías Congénitas/patología , Femenino , Genes Letales/genética , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Islas del Oceano Índico/epidemiología , Riñón/patología , Enfermedades Renales/genética , Enfermedades Renales/mortalidad , Enfermedades Renales/patología , Deformidades Congénitas de las Extremidades/mortalidad , Deformidades Congénitas de las Extremidades/patología , Masculino , Mutación/genética , Linaje , Fenotipo , Embarazo , Sindactilia/mortalidad , Sindactilia/patologíaRESUMEN
We report a case of a huge congenital pulmonary airway malformation (CPAM) that was referred as congenital diaphragmatic hernia (CDH). Initial ultrasound evaluation revealed a huge cystic lesion with septations, in the thorax, causing mediastinal shift and compression effects, suggesting the possibility of a thoracic lymphangioma, or bowel herniation with obstruction. A fetal magnetic resonance imaging reported possible bowel herniation through a posterior defect in the diaphragm, with volvulus, reinforcing the diagnosis of CDH. It was only on autopsy and subsequent histopathology examination that the diagnosis of a rare variant of CPAM-nonmucinous papillary type, could be made. To the best of our knowledge, a CPAM this huge has not been reported prenatally at this gestation. We recommend considering the potential diagnosis of CPAM in any thoracic cystic irrespective of its size or appearance.
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Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (AT1Rs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the AT1R blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone. Rodents express two AT1R isotypes: AT1Ra and AT1Rb. We previously demonstrated that AT1Rb is expressed at much higher levels compared with AT1Ra in cerebral pial arteries and is required for myogenic contractility in these vessels, whereas AT1Ra is unnecessary for this function. Here, we found that AT1Ra and AT1Rb are expressed at similar levels in parenchymal arterioles and that genetic knockout of AT1Ra blunted the ability of these vessels to generate myogenic tone. We also found that AT1Rb and total AT1R expression levels are much lower in parenchymal arterioles compared with pial arteries and that parenchymal arterioles are less sensitive to the vasoconstrictive effects of the endogenous AT1R ligand angiotensin II (ANG II). We conclude that 1) AT1Rs are critical for the initiation, but not the maintenance, of myogenic tone in parenchymal arterioles, and 2) lower levels of AT1Rb and total AT1R in parenchymal arterioles compared with pial arteries result in differences in myogenic and ANG II-induced vasoconstriction between these vascular segments.NEW & NOTEWORTHY Myogenic tone is critical for appropriate regulation of cerebral blood flow, but the mechanisms used by vascular smooth muscle cells to detect changes in intraluminal pressure are not fully characterized. Here, we demonstrate angiotensin II receptor type 1 (AT1R) is indispensable to initiation, but not maintenance, of myogenic tone in cerebral parenchymal arterioles. Furthermore, we demonstrate differences in AT1R expression levels lead to critical differences in contractile regulation between parenchymal arterioles and cerebral pial arteries.
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Circulación Cerebrovascular/fisiología , Microvasos/metabolismo , Receptor de Angiotensina Tipo 1/biosíntesis , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Arteriolas/metabolismo , Regulación de la Expresión Génica , Losartán/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Contracción Muscular/efectos de los fármacos , Tono Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Receptor de Angiotensina Tipo 1/genéticaRESUMEN
INTRODUCTION: A critical anti D antibody titre, defined for the conventional tube method of Indirect Coomb's test (ICT), when employed in the more sensitive column method could result in unnecessary referrals and frequent obstetric doppler scans. This study aimed to compare anti D titres by tube and column method in antenatal mothers, to assess their correlation with fetal anemia and to determine a critical titre for the column method. METHODS: Forty six antenatal mothers with anti D antibody were included in the study. Antibody titration was performed by serial twofold dilution of serum by both column and tube method and were correlated with middle cerebral artery peak systolic velocity (MCA PSV) measurement by Doppler ultrasonography. Receiver operating curve (ROC) was used to determine the cut-offs for critical titre by tube and column method in predicting fetal anemia. RESULTS: Column method had a median titre 3 fold higher than tube method. There was a significant association between fetal anemia by USG with median critical titres determined for both column (p = 0.031) and tube method (p = 0.016). ROC analysis showed the cut off for critical titres in column method as 64 with 90 % sensitivity, 72.7 % specificity and 75.38 % accuracy. CONCLUSIONS: The use of critical titre for anti D antibody, defined for the tube method, when applied to the column agglutination method would lead to increased referrals to specialized fetal medicine centres. Rather, an Anti D titre of 64 by column method can predict the likelihood of fetal anemia and should be considered as the critical titre to guide patient referrals.
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Pruebas de Aglutinación/métodos , Anticuerpos/sangre , Enfermedades Fetales/diagnóstico , Ultrasonografía Doppler/métodos , Adulto , Femenino , Feto , Humanos , EmbarazoRESUMEN
Testosterone is a key steroid hormone in the development of male reproductive tissues and the regulation of the central nervous system. The rapid signaling mechanism induced by testosterone affects numerous behavioral traits, including sexual drive, aggressiveness, and fear conditioning. However, the currently identified testosterone receptor(s) is not believed to underlie the fast signaling, suggesting an orphan pathway. Here we report that an ion channel from the transient receptor potential family, TRPM8, commonly known as the cold and menthol receptor is the major component of testosterone-induced rapid actions. Using cultured and primary cell lines along with the purified TRPM8 protein, we demonstrate that testosterone directly activates TRPM8 channel at low picomolar range. Specifically, testosterone induced TRPM8 responses in primary human prostate cells, PC3 prostate cancer cells, dorsal root ganglion neurons, and hippocampal neurons. Picomolar concentrations of testosterone resulted in full openings of the purified TRPM8 channel in planar lipid bilayers. Furthermore, acute applications of testosterone on human skin elicited a cooling sensation. Our data conclusively demonstrate that testosterone is an endogenous and highly potent agonist of TRPM8, suggesting a role of TRPM8 channels well beyond their well established function in somatosensory neurons. This discovery may further imply TRPM8 channel function in testosterone-dependent behavioral traits.
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Receptores Androgénicos/metabolismo , Canales Catiónicos TRPM/metabolismo , Testosterona/metabolismo , Calcio/metabolismo , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Células HEK293 , Humanos , Inmunohistoquímica , Inmunoprecipitación , Membrana Dobles de Lípidos/metabolismo , Unión Proteica/efectos de los fármacos , Testosterona/farmacología , Canales de Potencial de Receptor Transitorio/metabolismoAsunto(s)
Transposición de los Grandes Vasos/diagnóstico por imagen , Arterias Umbilicales/diagnóstico por imagen , Venas Umbilicales/diagnóstico por imagen , Adulto , Ecocardiografía , Ecocardiografía Doppler en Color , Femenino , Humanos , Embarazo , Tercer Trimestre del Embarazo , Ultrasonografía Doppler en Color , Ultrasonografía Prenatal , Cordón Umbilical/anomalías , Cordón Umbilical/diagnóstico por imagen , Venas Umbilicales/anomalíasRESUMEN
Some compact objects observed in gravitational wave events have masses in the gap between known neutron stars (NSs) and black holes (BHs). The nature of these mass gap objects is unknown, as is the formation of their host binary systems. We report pulsar timing observations made with the Karoo Array Telescope (MeerKAT) of PSR J0514-4002E, an eccentric binary millisecond pulsar in the globular cluster NGC 1851. We found a total binary mass of 3.887 ± 0.004 solar masses (Mâ), and multiwavelength observations show that the pulsar's binary companion is also a compact object. The companion's mass (2.09 to 2.71 Mâ, 95% confidence interval) is in the mass gap, indicating either a very massive NS or a low-mass BH. We propose that the companion formed in a merger between two earlier NSs.
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Introduction: Hypoxia-induced dilation of cerebral arteries orchestrated by Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) cation channels on endothelial cells is neuroprotective during ischemic stroke, but it is unknown if the channel has a similar impact during hemorrhagic stroke. TRPA1 channels are endogenously activated by lipid peroxide metabolites generated by reactive oxygen species (ROS). Uncontrolled hypertension, a primary risk factor for the development of hemorrhagic stroke, is associated with increased ROS production and oxidative stress. Therefore, we hypothesized that TRPA1 channel activity is increased during hemorrhagic stroke. Methods: Severe, chronic hypertension was induced in control (Trpa1 fl/fl) and endothelial cell-specific TRPA1 knockout (Trpa1-ecKO) mice using a combination of chronic angiotensin II administration, a high-salt diet, and the addition of a nitric oxide synthase inhibitor to drinking water. Blood pressure was measured in awake, freely-moving mice using surgically placed radiotelemetry transmitters. TRPA1-dependent cerebral artery dilation was evaluated with pressure myography, and expression of TRPA1 and NADPH oxidase (NOX) isoforms in arteries from both groups was determined using PCR and Western blotting techniques. In addition, ROS generation capacity was evaluated using a lucigenin assay. Histology was performed to examine intracerebral hemorrhage lesion size and location. Results: All animals became hypertensive, and a majority developed intracerebral hemorrhages or died of unknown causes. Baseline blood pressure and responses to the hypertensive stimulus did not differ between groups. Expression of TRPA1 in cerebral arteries from control mice was not altered after 28 days of treatment, but expression of three NOX isoforms and the capacity for ROS generation was increased in hypertensive animals. NOX-dependent activation of TRPA1 channels dilated cerebral arteries from hypertensive animals to a greater extent compared with controls. The number of intracerebral hemorrhage lesions in hypertensive animals did not differ between control and Trpa1-ecKO animals but were significantly smaller in Trpa1-ecKO mice. Morbidity and mortality did not differ between groups. Discussion: We conclude that endothelial cell TRPA1 channel activity increases cerebral blood flow during hypertension resulting in increased extravasation of blood during intracerebral hemorrhage events; however, this effect does not impact overall survival. Our data suggest that blocking TRPA1 channels may not be helpful for treating hypertension-associated hemorrhagic stroke in a clinical setting.
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Background This study aimed to determine whether mid-trimester fetal anterior abdominal wall subcutaneous tissue thickness (FASTT) is an early sonographic predictor of gestational diabetes mellitus (GDM), as well as to study its correlation with maternal glycemic values on GDM screening at 24-28 weeks. Methodology We conducted a prospective, case-control study. FASTT was assessed at anomaly scan in 896 uncomplicated singleton pregnancies. The 75-gram oral glucose tolerance test (OGTT) was done for all included patients at 24-28 weeks. Women diagnosed with GDM were taken as cases and appropriately matched in equal numbers as controls. Statistical analysis was done using SPSS version 20 (IBM Corp., Armonk, NY, USA). Independent-samples t-test, chi-square test, receiver operating characteristic curve, and Pearson's correlation coefficient (r) were performed wherever applicable. Results A total of 93 cases and 94 controls were included. Fetuses of women with GDM had significantly higher mean FASTT at 20 weeks (1.605 ± 0.328 mm vs. 1.222 ± 0.121 mm; p < 0.001). The FASTT cut-off obtained was 1.35 mm (sensitivity = 79.6%, specificity = 87.2%, positive predictive value = 86%, negative predictive value = 81.2%). There was a moderate positive correlation between fasting blood sugar (FBS) and two-hour OGTT values and FASTT (r = 0.332, p < 0.001 and r = 0.399, p < 0.001, respectively). FASTT >1.35 mm had an independent predictive value for GDM and was associated with a 19.608-fold increased risk of GDM. Conclusions FASTT values greater than 1.35 mm at 20 weeks are associated with a significantly increased risk of GDM. In addition, FASTT correlates with FBS and two-hour OGTT at 24-28 weeks and is a simple predictor of GDM at 18-20 weeks.
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BACKGROUND AND PURPOSE: Ultrasound-derived diagnosis of transverse venous sinus stenosis (TVSS) may have a promise given recent exploration of its role in pathophysiology of intracranial hypertension and availability of interventions like venous stenting. We investigated transverse venous sinus (TVS) insonation using transcranial color-coded duplex (TCCD) to establish normative values, inform on inherent physiological variability, and other measures to allow future studies on testing the construct validity of TCCD venous in diagnosing TVSS. METHODS: An institutional review board-approved prospective observational study evaluated 20 healthy volunteers to define TCCD-based measures for the TVS. Comparatively, the basal vein of Rosenthal, deep middle cerebral veins, and internal jugular veins were insonated. We report on physiological variability including the intrasubject, intersubject, and side-to-side variability; gradient of TVS velocities on each side from medial to lateral insonation; and the relationship between TVS and other insonated venous structures. RESULTS: Fifteen out of 20 subjects had the TVS insonated bilaterally, and five had unilaterally (four right, one left). TVS velocities had comparable intrasubject variability to other intracranial veins insonated and lower velocity-based variability than the pulsatility index. There was significant side-side variability in TVS-derived measures without discernible patterns. Insonating TVS from medial to lateral revealed a gradient with a bimodal peak in ultrasound-derived velocities. We did not find discernible relationships between TVS and other veins for TCCD-derived measures. CONCLUSIONS: These results can inform future studies validating the normative values in a larger sample and help explore the role of TCCD venous in the diagnosis of venous sinus stenosis.
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Venas Cerebrales , Senos Paranasales , Humanos , Ultrasonografía Doppler en Color/métodos , Constricción Patológica , Ultrasonografía Doppler Transcraneal/métodos , Venas Cerebrales/diagnóstico por imagen , Velocidad del Flujo Sanguíneo/fisiología , Circulación CerebrovascularRESUMEN
Introduction: Disturbances in placentation increase the risk of maternal and fetal complications. Several biochemical and imaging modalities have been studied, but the hunt for a single effective screening test never became a reality as the causes of this complex condition are multifactorial and polygenetic, many of which we are only beginning to discover. Not many studies have been conducted in the developing countries like India and other low resource settings to consider whether it would be worthwhile to combine inexpensive and effective markers together for better prediction of adverse pregnancy outcome.This study primarily aims to investigate the predictability of combined screening with maternal serum homocysteine and second trimester uterine artery Doppler in diagnosis of adverse pregnancy outcome. Methodology: A prospective cohort study which involved 100 women with singleton gestation, meeting the inclusion criteria, attending the inpatient or outpatient of Obstetrics and Gynaecology in Amrita Institute of Medical Sciences, Kerala, a tertiary care centre in Southern India from July 2016 and September 2018 was conducted. Serum Homocysteine estimation (tHcy) was done between 18 and 28 weeks of gestation with informed consent, and uterine artery (UA) Doppler PI which is a non-invasive routine study was done along with targeted second trimester anomaly scan (18-24 weeks) in Fetal Medicine Department. Cutoff values of tHcy and UA PI were computed at 95th (> / = 9.7 mmol/l) and 90th percentile, respectively as reported by Onalan et al. [9] and Nicholaides et al. [4]. Statistical analysis was performed using IBM SPSS version 20.0 software. Chi-square test and diagnostic measures were also used. Results: Of the 100 patients, 15% (n = 15) developed hypertensive disorder. 7% (n = 7) had FGR and 7%(n = 7) had spontaneous preterm birth. 6% (n = 6) neonates had an APGAR score < 7 and 8% neonates (n = 8) required immediate NICU admission. Statistically significant association was found when tHcy and UA PI were used together for the prediction of FGR (p = 0.003), preterm birth (p = 0.002) and low APGAR score at birth (p = 0.009) with a specificity of 83.4%. With regard to PIH, both parameters were found to be statistically significant only when used independently (p = 0.001) but not when used in combination (p = 0.17). Both elevated tHcy and abnormal UA PI used in combination predicted adverse pregnancy outcome like FGR but with a low sensitivity of 14.3% and high specificity of 98.9%. However, when used independently these markers predicted FGR with a better sensitivity (tHcy- 28.6% and UA PI- 44.4%). Conclusion: Findings from this study have been promising with potential clinical implications for the diagnosis and management of high-risk pregnancies. Though the independent role of the two markers in screening various adverse pregnancy outcomes could be proved, their combined use to improve predictivity of more complications warrants further studies on a larger population with appropriate randomisation.
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Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate the membrane potential and contractility of vascular smooth muscle cells (VSMCs). The mechanisms responsible for these membrane interactions are poorly understood. In many cells, STIM1 (stromal interaction molecule 1), a single-transmembrane-domain protein that resides in the endoplasmic reticulum (ER), transiently moves to ER-PM junctions in response to depletion of ER Ca2+ stores and initiates store-operated Ca2+ entry (SOCE). Fully differentiated VSMCs express STIM1 but exhibit only marginal SOCE activity. We hypothesized that STIM1 is constitutively active in contractile VSMCs and maintains peripheral coupling. In support of this concept, we found that the number and size of SR-PM interacting sites were decreased, and SR-dependent Ca2+-signaling processes were disrupted in freshly isolated cerebral artery SMCs from tamoxifen-inducible, SMC-specific STIM1-knockout (Stim1-smKO) mice. VSMCs from Stim1-smKO mice also exhibited a reduction in nanoscale colocalization between Ca2+-release sites on the SR and Ca2+-activated ion channels on the PM, accompanied by diminished channel activity. Stim1-smKO mice were hypotensive, and resistance arteries isolated from them displayed blunted contractility. These data suggest that STIM1 - independent of SR Ca2+ store depletion - is critically important for stable peripheral coupling in contractile VSMCs.
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Calcio , Músculo Liso Vascular , Animales , Calcio/metabolismo , Señalización del Calcio , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Retículo Sarcoplasmático/metabolismo , Molécula de Interacción Estromal 1/genética , Molécula de Interacción Estromal 1/metabolismoRESUMEN
Fetal ventriculomegaly (VM) refers to the abnormal enlargement of one or more ventricles of the brain in-utero. The enlargement may or may not be related to ventricular obstruction and increased intracranial pressure; therefore, the term "hydrocephalus" is not used. VM is diagnosed usually in the mid-trimester when the atrial diameter (AD) of the lateral ventricle is more than 10 mm on one or both sides. A thorough workup is then required to identify the cause as the etiology is diverse. Fetal magnetic resonance imaging (MRI) may yield additional information. Serial ultrasound follow-up would be required to assess its progression with advancing gestation. The prognosis and long-term outcomes greatly depend upon the etiology, the severity at diagnosis, progression, and associations. This article reviews the definitions, diagnosis, and workup of fetal VM, discusses follow-up protocols and prognosis, and examines the role of fetal therapy, including fetoscopic surgery in its prenatal management.