Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin-angiotensin system is disrupted, and hypertension and endothelial dysfunction contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient individuals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine.
Blood Pressure* ; Calcitriol ; Cardiovascular Diseases ; Diet ; Homeostasis ; Humans ; Hypertension ; Incidence ; Life Style ; Receptors, Calcitriol ; Renin-Angiotensin System ; Risk Factors ; Solar System ; Vitamin D Deficiency ; Vitamin D* ; Vitamins

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

In newborn infants, normal adrenal glands are characterized by a relatively thin echogenic center surroundedby a thick, hypoechoic cortical rim as seen on ultrasound (US). Various disorders involving the neonatal adrenalgland include adrenal hemorrhage, hyperplasia, cyst, Wolman's disease, and congenital neuroblastoma. Adrenalhemorrhage is the most common cause of an adrenal mass in the neonate, though differentiation between adrenalhemorrhage and neuroblastoma is in many cases difficult. We describe characteristic US, CT and MR imaging findingsin neonates with various adrenal disorders.
Adrenal Glands ; Hemorrhage ; Humans ; Hyperplasia ; Infant, Newborn ; Magnetic Resonance Imaging ; Neuroblastoma ; Ultrasonography ; Wolman Disease

In newborn infants, normal adrenal glands are characterized by a relatively thin echogenic center surroundedby a thick, hypoechoic cortical rim as seen on ultrasound (US). Various disorders involving the neonatal adrenalgland include adrenal hemorrhage, hyperplasia, cyst, Wolman's disease, and congenital neuroblastoma. Adrenalhemorrhage is the most common cause of an adrenal mass in the neonate, though differentiation between adrenalhemorrhage and neuroblastoma is in many cases difficult. We describe characteristic US, CT and MR imaging findingsin neonates with various adrenal disorders.
Adrenal Glands ; Hemorrhage ; Humans ; Hyperplasia ; Infant, Newborn ; Magnetic Resonance Imaging ; Neuroblastoma ; Ultrasonography ; Wolman Disease

The method of single-cell RNA sequencing has been rapidly developed, and numerous experiments have been conducted over the past decade. Their results allow us to recognize various subpopulations and rare cell states in tissues, tumors, and immune systems that are previously unidentified, and guide us to understand fundamental biological processes that determine cell identity based on single-cell gene expression profiles. However, it is still challenging to understand the principle of comprehensive gene regulation that determines the cell fate only with transcriptome, a consequential output of the gene expression program. To elucidate the mechanisms related to the origin and maintenance of comprehensive single-cell transcriptome, we require a corresponding single-cell epigenome, which is a differentiated information of each cell with an identical genome. This review deals with the current development of single-cell epigenomic library construction methods, including multi-omics tools with crucial factors and additional requirements in the future focusing on DNA methylation, chromatin accessibility, and histone post-translational modifications. The study of cellular differentiation and the disease occurrence at a single-cell level has taken the first step with single-cell transcriptome and is now taking the next step with single-cell epigenome.

Ion channel inhibitors are widely used for pharmacological discrimination between the different channel types as well as for determination of their functional role. In the present study, we tested the hypothesis that 4-aminopyridine (4-AP) could affect the large conductance Ca2+ -activated K+ channel (BKCa) currents using perforated-patch or cell-attached configuration of patch-clamp technique in the rabbit pulmonary arterial smooth muscle. Application of 4-AP reversibly inhibited the spontaneous transient outward currents (STOCs). The reversal potential and the sensitivity to charybdotoxin indicated that the STOCs were due to the activation of BKCa. The BKCa currents were recorded in single channel resolution under the cell-attached mode of patch-clamp technique for minimal perturbation of intracellular environment. Application of 4-AP also inhibited the single BKCa currents reversibly and dose-dependently. The membrane potential of rabbit pulmonary arterial smooth muscle cells showed spontaneous transient hyperpolarizations (STHPs), presumably due to the STOC activities, which was also inhibited by 4-AP. These results suggest that 4-AP can inhibit BKCa currents in the intact rabbit vascular smooth muscle. The use of 4-AP as a selective voltage-dependent K+ (KV) channel blocker in vascular smooth muscle, therefore, must be reevaluated.
4-Aminopyridine* ; Charybdotoxin ; Discrimination (Psychology) ; Ion Channels ; Membrane Potentials ; Muscle, Smooth* ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle* ; Patch-Clamp Techniques ; Pulmonary Artery

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine (10~100 µM) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine (30 µM), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-HT(2A) receptor inhibitor, indicating that ketamine facilitated the activation of 5-HT(2A) receptors. Anpirtoline and BW723C86, selective agonists of 5-HT(1B) and 5-HT(2B) receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-HT(2A) receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-HT(2A) receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.
Animals ; Arteries ; Blood Pressure ; Humans ; Hypertension ; Ketamine* ; Ketanserin ; Mesenteric Arteries* ; Models, Animal ; Norepinephrine ; Rats* ; Receptor, Serotonin, 5-HT2A ; Schizophrenia ; Serotonin ; Shock ; Vasoconstriction