Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients.

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

MiRNA Expression is Associated with Clinical Variables Related to Vascular Remodeling in the Kidney and the Brain in Type 2 Diabetes Mellitus Patients.

Background: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.Methods: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio (UACR), biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. MiRNA were quantified in blood and urine by a real-time PCR System. Cerebrovascular ultrasound measurements were performed in the carotid and middle cerebral arteries.Results: MiRNA21 and miRNA124 correlated positively with nephrin, podocalyxin, synaptopodin, urinary N-acetyl-D-glucosaminidase (NAG), urinary kidney-injury molecule-1 (KIM-1), UACR, and negatively with eGFR; miRNA125a, 126, 146a, 192 correlated negatively with nephrin, podocalyxin, synaptopodin, urinary NAG, urinary KIM-1, UACR, and directly with eGFR. Plasma miRNA-21 and miRNA192 correlated directly with cerebral hemodynamics parameters of atherosclerosis and arteriosclerosis. MiRNA-124, 125a, 126, 146a showed negative correlations with the same parameters.Conclusions: In Type 2 diabetes patients there is an association of vascular remodeling in the brain and the kidney with a specific miRNAs pattern. Cerebrovascular changes occur even in normoalbuminuric patients, with 'high-to-normal' levels of podocyte injury and PT dysfunction biomarkers. These phenomena may be explained by the variability of miRNA expression within the two organs in early DKD.

Vitamin D improves vascular function and decreases monoamine oxidase A expression in experimental diabetes.

The active form of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), was reported to improve vascular function in patients with diabetes, yet the underlying mechanisms remain to be fully elucidated. Monoamine oxidase (MAO), a mitochondrial enzyme, with two isoforms (A and B) that generates hydrogen peroxide (H2O2) as by-product, has been recently reported to contribute to the pathogenesis of endothelial dysfunction in diabetes. The present study assessed the interaction between vitamin D and MAO in the vascular wall in the setting of type 1 experimental diabetes. To this aim, diabetes was induced in male Wistar rats via a single injection of streptozotocin (STZ, 50 mg/kg, IP) and 1 month later thoracic aortas were harvested and used for organ bath studies and H2O2 measurements. MAO expression was assessed by immunohistochemistry and RT-PCR. Endothelial function was evaluated in isolated aortic rings in the absence vs. presence of 1,25(OH)2D3 (100 nM, 24 h incubation). In diabetic animals, we found a significant reduction in the endothelial-dependent relaxation to acetylcholine and an increased expression of the MAO-A isoform, respectively. Vitamin D significantly improved vascular function, mitigated oxidative stress and decreased MAO-A expression in diabetic vascular preparations. In conclusion, MAO-A is induced in diabetic aortas and vitamin D can improve diabetes-induced endothelial dysfunction by modulating the MAO-A expression.

Therapy with atorvastatin versus rosuvastatin reduces urinary podocytes, podocyte-associated molecules, and proximal tubule dysfunction biomarkers in patients with type 2 diabetes mellitus: a pilot study.

BACKGROUND: Diabetic nephropathy is a severe complication of Type 2 diabetes. Tubular lesions may play an important role in its early stages. The aim of our study was to determine if atorvastatin protects the podocytes and the proximal tubule in patients with Type 2 diabetes. METHODS: A total of 63 patients with Type 2 diabetes completed this 6-months prospective pilot study. They were randomized to continue rosuvastatin therapy (control group) or to be administered an equipotent dose of atorvastatin (intervention group), and were assessed regarding urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. RESULTS: The patients from the intervention group presented a significant reduction in podocyturia (from 7.0 to 4.0 cells/ml, p < .05), urinary nephrin (from 1.7 to 1.3 mg/g, p < .001), urinary vascular endothelial growth factor (from 262.8 to 256.9, p < .01), urinary alpha1-microglobulin (from 10.0 to 8.3 mg/g, p < .01), urinary kidney injury molecule-1 (from 139.5 to 136.3 ng/g, p < .001), and urinary advanced glycation end-products (from 112.6 to 101.3 pg/ml, p < .001). Podocyturia correlated directly with the podocyte damage biomarkers, proximal tubule dysfunction biomarkers, albumin to creatinine ratio, and advanced glycation end-products, and inversely with the glomerular filtration rate. CONCLUSIONS: In patients with Type 2 diabetes, atorvastatin exerts favorable effects on the kidney. There is a correlation between the evolution of the podocytes and of the proximal tubule biomarkers, supporting the hypothesis that the glomerular changes parallel proximal tubule dysfunction in the early stages of diabetic nephropathy.

Age and HPV type as risk factors for HPV persistence after loop excision in patients with high grade cervical lesions: an observational study.

BACKGROUND: Persistent infections with high risk human papillomaviruses (HR-HPV) cause virtually all cervical cancers. METHODS: An observational study was conducted aiming to estimate the rate of HPV infection persistence after LEEP in patients with high grade squamous intraepithelial lesions (HSIL). Moreover, the study investigated if persistence is age related. For this reason a total of 110 patients were included between January 2010 and June 2015. RESULTS: At 6 months after LEEP the overall HPV infection persistence rate was 40.9 %, at 12 months 20 % and at 18 months 11.8 %. Type 16 showed the highest persistence rate: 27.3 % at 6 months, 12.7 % at 12 months and 10 % at 18 months after LEEP. The persistence for HPV type 16 at 6 months after LEEP was significantly higher in the group > =36.5 years old compared to the persistence rate in the group <36.5 years old (p = 0.0027, RR = 2.75, 95 %ϵ(1.34; 5.64)) (see Table 3). CONCLUSIONS: LEEP does not completely eradicate HPV infection. HPV persistence rate after LEEP is higher in infections with type 16 and in women older than 36.5 years.

Human Papilloma Virus Persistence after Cone Excision in Women with Cervical High Grade Squamous Intraepithelial Lesion: A Prospective Study.

Background. Persistent human papillomavirus (HPV) infection is a necessary event in cervical cancer tumorigenesis. Our objectives were to estimate the rate of HPV infection persistence after large loop excision of the transformation zone (LEEP) in patients with high grade squamous intraepithelial lesions (HSIL) and to investigate if HPV persistence is type related. Methods. We conducted a prospective study on 89 patients with HSIL treated with LEEP. DNA HPV was performed before surgery and at 6, 12, and 18 months after LEEP. Results. Four patients were excluded from the study. The HPV persistence in the remaining 85 patients was 32.95% (6 months), 14.12% (12 months), and 10.59% (18 months). Type 16 had the highest persistence rate, 23.5% (6 months), 11.8% (12 months), and 8.2% (18 months). Coinfection was found to be 54.12% before LEEP and 18.8% (6 months), 4.7% (12 months), and 3.5% (18 months) after LEEP. The rate of coinfections including type 16 was 46.83% of all coinfections. Coinfection including type 16 was not correlated with higher persistence rate compared to infection with type 16 only. Conclusions. HPV infection is not completely eradicated by LEEP in patients with HSIL lesion on PAP smear. HPV persistence after LEEP is influenced by HPV type. HPV type 16 has the highest persistence rate.

Skull base connections between the middle meningeal and internal carotid arteries.

BACKGROUND: External to internal carotid artery anastomoses are normally found in man. However, such connections at the skull base between the cavernous internal carotid artery and middle meningeal artery are rarely discussed in the literature and when present, are difficult, if not impossible, to see with imaging studies unless pathologically enlarged. Therefore, the aim of the present anatomic study was to investigate such connections via cadaveric dissection. MATERIALS AND METHODS: In 12 latex-injected adult cadaveric heads (24 sides), microdissection was performed to investigate for connections at the skull base between the cavernous part of the internal carotid and middle meningeal arteries. Additionally, neck dissections were performed to observe for atherosclerosis of the internal carotid artery. Statistical analyses were performed for differences between sides and gender. RESULTS: On 14 sides (58.3%) (nine left and five right sides), arterial anastomoses were identified between the middle meningeal and internal carotid arteries. All connections were small with a mean length of 8 mm and a mean diameter of 0.9 mm. These connections were found between the lateral aspect of the cavernous internal carotid artery and the medial side of the main trunk of the middle meningeal artery on 64.3% of sides, the anterior branch of the middle meningeal artery on 7% of sides, and the posterior branch of the middle meningeal artery on 28.6% of sides. The size of the middle meningeal and internal carotid arteries was within normal limits in all specimens. Although not statistically significant, connections tended to be more frequently found on the left sides. CONCLUSIONS: The majority of cadaveric sides in our study were found to have anastomoses at the skull base between the cavernous segment of the internal carotid and middle meningeal arteries. These very small connections would most likely not be visualized on imaging studies. These connections most likely function in times of carotid artery ischemia that is chronic in nature (e.g., Moya Moya disease) and may, in the past, have been misidentified as a human rete mirabile.

Analysis of the tortuosity of the internal carotid artery in the cavernous sinus.

BACKGROUND: The morphology of the internal carotid artery at the skull base is important in radiologic interpretation, surgery, and more recently, endovascular interventional and diagnostic procedures. Therefore, a thorough knowledge of the shape of the carotid siphon can be important in the clinical realm. METHODS: In this study, we evaluated the shape of the carotid siphon from a lateral perspective on cerebral angiography. These shapes were then correlated to the Lang and Reiter classification. RESULTS: Types A, B, and C were distributed as follows: type A 12 (30%), B 16 (40%), 12 (30%). There was no significant difference (p > 0.05) in patient ages between the three types (type A 54.6 ± 14.2 years, type B 55.1 ± 14.9 years, and type C 52.7 ± 16.9 years). Normalized for gender disproportion, there was no significant gender predominance for any type (type A female:male = 1.4:1; type B female:male = 1.1:1; type C female:male = 0.7:1). CONCLUSIONS: Such a classification scheme with additional application in another group might be of use to future studies aimed at the morphology of the cavernous part of the internal carotid artery.

Occipital neuralgia: anatomic considerations.

Occipital neuralgia is a debilitating disorder first described in 1821 as recurrent headaches localized in the occipital region. Other symptoms that have been associated with this condition include paroxysmal burning and aching pain in the distribution of the greater, lesser, or third occipital nerves. Several etiologies have been identified in the cause of occipital neuralgia and include, but are not limited to, trauma, fibrositis, myositis, fracture of the atlas, and compression of the C-2 nerve root, C1-2 arthrosis syndrome, atlantoaxial lateral mass osteoarthritis, hypertrophic cervical pachymeningitis, cervical cord tumor, Chiari malformation, and neurosyphilis. The management of occipital neuralgia can include conservative approaches and/or surgical interventions. Occipital neuralgia is a multifactorial problem where multiple anatomic areas/structures may be involved with this pathology. A review of these etiologies may provide guidance in better understanding occipital neuralgia.

Fusiform aneurysm of a persistent trigeminal artery associated with rare intracranial arterial variations and subarachnoid hemorrhage.

The trigeminal artery is one of four primitive anastomoses between the internal carotid artery and vertebrobasilar system that regresses in the sixth week of fetal development. A persistent trigeminal artery (PTA) is generally an incidental finding but may also be associated with intracranial vascular pathologies such as aneurysms, arteriovenous malformations, and cranial nerve compression syndromes. We present an extremely rare case of a right PTA with an associated bleeding fusiform aneurysm located in the carotidian (lateral) part of the PTA. In addition, this rare anatomic variation was associated with bilateral absence of the posterior communicating arteries, a left posterior cerebral artery originating from the left internal carotid artery, and agenesis of the A1 segment of the left anterior cerebral artery.

Right lump kidney with varied vasculature and urinary system revealed by multidetector computed tomographic (MDCT) angiography.

Renal ectopia also known as ectopic kidney is an embryological renal anomaly characterised by abnormal anatomical location of one or both of the kidneys. This can occur in various forms such as (1) crossed fused renal ectopia, (2) ectopic thoracic kidney and (3) pelvic kidneys. The lump kidney is one of the six variations of crossed fused ectopic kidney. Throughout life, the patient may remain asymptomatic, however, symptomatic patients may present with minor traumatic injuries due to the abnormal location or normal kidney pathologies. During normal embryological development, there is cephalic migration during which the kidneys ascend to their normal retroperitoneal location; therefore, an ectopic location is as a result of arrested migration. During this embryological development the kidney has multiple aorto-illiac branches, which degenerate when the kidney reaches its normal location. Here they develop new renal branches from the aorta and during an arrested ascent the ectopic kidney tends to retain some of the older aorto-iliac vessels. Hence, the arterial supply and the veineux drainage are grossly abnormal, reflecting the metanephric malascent and the primitive vascular arrangement. The collecting systems also present with important anatomical variations. We present an extremely rare case of right lump kidney with six renal arteries, two renal veins and two duplicated pelvicalyceal systems.

A case of bilateral tracheal bronchus: report of a rare association in multidetector computed tomography bronchoscopy.

Bilateral tracheal bronchus is a rare variation of the tracheobronchial tree. We present a 1-year 7-month-old male patient who presented with sepsis following endotracheal intubation. Upon review of multidetector computed tomography images, the patient was diagnosed with displaced bilateral tracheal bronchus. Imaging showed a right-sided anomalous bronchus arising 0.9 cm proximal to the carina. The left-sided anomalous bronchus arose 0.7 cm proximal to the carina, mimicking a tracheal trifurcation. When viewed together, the close proximity of both the right and left tracheal bronchi to the carina created a distinct tracheal quadrifurcation. This rare anatomic variation was additionally associated with an anorectal malformation (anal atresia). Unrecognized tracheal bronchus in patients undergoing endotracheal intubation can lead to serious complications. While bilateral tracheal bronchus is described in the literature, we are unaware of any case similar to this patient presentation. We present and analyze this unusual case of bilateral tracheal bronchus. The anatomy and clinical significance of this variation is then discussed.

Persistent hypoglossal artery aneurysm located in the hypoglossal canal with associated subarachnoid hemorrhage.

The hypoglossal artery is one of four primitive anastomoses between the internal carotid artery and vertebrobasilar system that regresses in the sixth week of fetal development. A persistent hypoglossal artery (PHA) is generally an incidental finding but may also be associated with aneurysms or arteriovenous malformations. We present a rare case of a PHA with an associated bleeding intracranial PHA aneurysm located in the hypoglossal canal.

The neurologist's dilemma: a comprehensive clinical review of Bell's palsy, with emphasis on current management trends.

BACKGROUND: Recent advances in Bell's palsy (BP) were reviewed to assess the current trends in its management and prognosis. MATERIAL/METHODS: We retrieved the literature on BP using the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar. Key words and phrases used during the search included 'Bell's palsy', 'Bell's phenomenon', 'facial palsy', and 'idiopathic facial paralysis'. Emphasis was placed on articles and randomized controlled trails (RCTs) published within the last 5 years. RESULTS: BP is currently considered the leading disorder affecting the facial nerve. The literature is replete with theories of its etiology, but the reactivation of herpes simplex virus isoform 1 (HSV-1) and/or herpes zoster virus (HZV) from the geniculate ganglia is now the most strongly suspected cause. Despite the advancements in neuroimaging techniques, the diagnosis of BP remains one of exclusion. In addition, most patients with BP recover spontaneously within 3 weeks. CONCLUSIONS: Corticosteroids are currently the drug of choice when medical therapy is needed. Antivirals, in contrast, are not superior to placebo according to most reliable studies. At the time of publication, there is no consensus as to the benefit of acupuncture or surgical decompression of the facial nerve. Long-term therapeutic agents and adjuvant medications for BP are necessary due to recurrence and intractable cases. In the future, large RCTs will be required to determine whether BP is associated with an increased risk of stroke.

Variations of the tracheobronchial tree: anatomical and clinical significance.

Tracheobronchial variations can be found during routine bronchoscopy or computed tomography. Previous sources estimate an incidence of 1-12%; however, these variations are often asymptomatic. Symptomatic patients present typically with cough and lower respiratory tract infection. Knowledge and understanding of tracheobronchial variations have important implications for diagnosis of symptomatic patients and performing certain procedures, including bronchoscopy and endotracheal intubation. In this review, we describe the most commonly encountered variations, tracheal bronchus and accessory cardiac bronchus, along with three minor abnormalities of this region. We also review the various imaging modalities in the diagnosis and treatment of these conditions.

Ectopia cordis: a rare congenital anomaly.

Ectopia cordis (EC) is a rare congenital anomaly associated with the heart positioned outside of the thoracic cavity either partially or completely. The ectopic heart can be found along a spectrum of anatomical locations, including the cervical, thoracic and abdominal regions and in most cases, it protrudes outside the chest through a split sternum. Although the first case of EC was identified during the early 1600s only 91 cases have been reported since then in the literature. This review will discuss the history and prevalence of EC, its etiology, morphology, presentation and symptoms, complications, diagnosis, treatment and management and prognosis.

Anatomical significance in aortoiliac occlusive disease.

Aortoiliac occlusive disease is a subset of peripheral arterial disease involving an atheromatous occlusion of the infrarenal aorta, common iliac arteries, or both. The disease, as it is known today, was described by the French surgeon René Leriche as a thrombotic occlusion of the end of the aorta. Leriche successfully linked the anatomic location of the occlusion with a unique triad of symptoms, including claudication, impotence, and decreased peripheral pulses. The anatomical location of the atheromatous lesions also has a direct influence on classification of the disease, as well as choice of treatment modality. Considering its impact on diagnosis and treatment, we aimed to provide a detailed understanding of the anatomical structures involved in aortoiliac occlusive disease. Familiarity with these structures will aid the physician in interpretation of radiologic images and surgical planning.

Betulinic acid in complex with a gamma-cyclodextrin derivative decreases proliferation and in vivo tumor development of non-metastatic and metastatic B164A5 cells.

Betulinic acid, a very promising anti-melanoma agent, has very low water solubility that causes low bioavailability. To overcome this inconvenience, a highly water-soluble cyclodextrin was used (octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonic acid)]-γ-cyclodextrin). The complex was physico-chemically analyzed using differential scanning calorimetry (DSC), X-ray and scanning electron microscopy (SEM) methods and then in vitro tested for its antiproliferative activity by the MTT assay and by cell cycle analysis. Finally, the complex was tested in vivo using an animal model of murine melanoma developed in C57BL/6J mice, where it caused a reduction in tumor volume and weight. The study revealed the beneficial influence of betulinic acid inclusion into the cyclodextrin in terms of antiproliferative activity and in vivo tumor development.

Common stem origin of left gastric, right and left inferior phrenic arteries, in association with a hepatosplenomesenteric trunk, independently arising from the abdominal aorta: case report using MDCT angiography.

We describe in this paper a rare case of a 45-year-old male with a common stem origin of the left gastric artery (LGA), right inferior phrenic artery (RIPA), and left inferior phrenic artery (LIPA), in association with the presence of a hepatosplenomesenteric trunk (HSMT) arising from the abdominal aorta (AA), as revealed by routine multidetector computed tomography (MDCT) angiography. The common stem origin of the LGA, RIPA, and LIPA had an endoluminal diameter of 3.3 mm, the LGA of 2.8 mm. The endoluminal diameter of the RIPA and LIPA was at the origin of approximately 1 mm, complicating selective chemoembolization of the liver parenchyma.

An unusual origin of the celiac trunk and the superior mesenteric artery in the thorax.

The authors report a case of a 44-year-old male found to have unusual origins of the celiac trunk (CT) and superior mesernteric artrery (SMA) as revealed by routine multidetector computed tomograph (MDCT) angiography. The CT and SMA originate from the thoracic aorta (TA) 21 mm and 9 mm above the aortic hiatus, respectively. The median arcuate ligament (MAL) is located at the level of the L1-L2 intervertebral disc. The course of the CT descends in the thoracic cavity making a 14° acute downward angle in front of the TA; below the level of the MAL, the CT descends, making an angle of 47°. The course of the SMA descends at both the thoracic and abdominal level making an angle of 17°, and having an aortomesenteric distance of 9 mm at the level of the third part of the duodenum. In the present case, the supradiaphragmatic origin of the CT and the SMA was determined by their incomplete caudal descent, associated with a pronounced apparent descent of the diaphragm. A thoracic origin of the CT and SMA and the acute downward aortomesenteric angle (17°) associated with a reduced aortomesenteric distance at the level of the third part of the duodenum (9 mm), although no clinical signs are present, may predispose the patient to develop simultaneously a triple syndrome: the compression of CT by MAL (celiac axis compression syndrome), the compression of SMA by MAL (superior mesenteric artery compression syndrome), and the compression of the duodenum by the SMA (superior mesenteric artery syndrome).