Recently non-coding RNA (ncRNA) genes have been found to serve many important functions in the cell such as regulation of gene expression at the transcriptional level.Potentially there are more ncRNA molecules yet to be found and their possible functions are to be revealed.The discovery of ncRNAs is a difficult task because they lack sequence indicators such as the start and stop codons displayed by protein-coding RNAs.Current methods utilize either sequence motifs or structural parameters to detect novel ncRNAs within genomes.Here,we present an ab initio ncRNA finder,named ncRNAscout,by utilizing both sequence motifs and structural parameters.Specifically,our method has three components:(i) a measure of the frequency of a sequence,(ii) a measure of the structural stability of a sequence contained in a t-score,and (iii) a measure of the frequency of certain patterns within a sequence that may indicate the presence of ncRNA.Experimental results show that,given a genome and a set of known ncRNAs,our method is able to accurately identify and locate a significant number of ncRNA sequences in the genome.The ncRNAscout tool is available for downloading at http://bioinformatics.njit.edu/ncRNAscout.

The non-structural 5B (NS5B) gene is the target region to identify hepatitis C virus (HCV) subtypes. However, it is not always possible to amplify this region because of inherently high sequence variability. Nucleotide sequences of the non-structural 5A (NS5A) and NS5B genes and its concordance were determined from patients infected with HCV genotype 1 (HCV-1). Among the 30 HCV-1 samples, 7 (23%) were identified as subtype 1a and 23 (77%) were identified as 1b by NS5A sequencing. Sequence analysis of the NS5B showed that 13 (43%) were identified as 1a and 17 (57%) were identified as 1b. Out of the 13 samples identified as 1a by NS5B, 6 (46%) were correctly identified by NS5A. Of the 17 samples identified as 1b by NS5B, 16 (94%) were correctly identified by NS5A. The presence of glutamic acid (E) or aspartic acid (D) at position 2225 in the NS5A differentiates 1a from 1b subtypes, respectively. This study showed that the NS5A sequencing can identify HCV-1a and 1b subtypes with predictive values of 86% and 70% of cases, respectively. The overall concordance with NS5B was 73%. NS5B sequence analysis remains to be the reference method to identify HCV-1 subtypes. NS5A sequencing may be used to complement NS5B sequencing in case the NS5B gene cannot be successfully amplified.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; ; Aspartic Acid ; Genotype ; Glutamic Acid ; Hepacivirus ; Hepatitis C ; Nucleotides ; Sequence Analysis ; Viral Nonstructural Proteins

Hiccups are a benign physiological feature affecting almost everyone at one time or another. They tend to be short-lived and do not affect quality of life; however, there are various pathologies that may present with long-lasting hiccups. These are grouped into 3 categories according to their duration: acute, persistent and intractable or protracted hiccups. Intractable hiccups last longer than 2 months and are usually associated with more severe conditions. The association between intractable hiccups and reflux disease has not been previously documented by objective methods. This report describes the case of a 23-year-old female who presented with protracted hiccups; all other organic pathologies were ruled out, and endoscopy and conventional pH-metry confirmed a diagnosis of non-erosive reflux disease as the unique cause.
2-Pyridinylmethylsulfinylbenzimidazoles ; Electric Impedance ; Endoscopy ; Female ; Gastroesophageal Reflux ; Hiccup ; Humans ; Proton Pump Inhibitors ; Young Adult

The global epidemic of diabetes and tuberculosis poses challenges to the control of both diseases. Patients with tuberculosis and diabetes experience worse clinical manifestations, increased risk of treatment failure, recurrence, and death. Diabetes is also associated with risk for latent tuberculosis infection. Management of hyperglycemia reduces the risk and improves the outcome of tuberculosis in diabetic patients. Recent epidemiological studies from Taiwan have provided new and important information on the benefits of metformin in tuberculosis. When addressing the issue of multidrug-resistant tuberculosis, a shortened anti-tuberculous therapeutic regime seems a feasible approach for better cure rates, with less loss-to-follow.

Objective: This study investigated the effect of brimonidine on the anterior-chamber angle in eyes with narrow angles using noncontact three-dimensional anterior-segment analyzer Pentacam. Methods: Nine eyes with narrow angles were distributed to one of three treatment groups—single topical dose of 0.15% brimonidine tartrate, 0.5% timolol maleate (positive control), or balanced salt solution (negative control)—in a prospective, single-masked, crossover, comparative trial. The primary outcome measure was anterior-chamber angle at baseline, and 2 and 4 hours after instillation of the treatment drug. Secondary outcome measures were pupil diameter, intraocular pressure (IOP), and anterior-chamber depth and volume. After a two-week washout period, eyes were crossed over to the other treatment modes. All baseline and posttreatment measurements were taken. Repeated analysis of variance (ANOVA) was used for statistical analysis. Results: Anterior-chamber angle, depth, and volume did not differ significantly for all treatment groups. Brimonidine caused a significant decrease in pupil diameter, most notably 2 hours after instillation, from baseline of 2.36 ± 0.37 mm to 2.17 ± 0.35 mm. (p = 0.03). There was a significant decrease in IOP from baseline to hour 4 after treatment for both brimonidine (11.4 ± 2.2 to 9 ± 1.8 mm Hg, p < 0.001) and timolol (11.9 ± 2.3 to 9.4 ± 2.1 mm Hg, p = 0.003). Conclusions Brimonidine produced a miotic trend with no significant opening of the anterior-chamber angle in patients with narrow angles.
Brimonidine Tartrate ; Miosis ; Intraocular Pressure

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
Adrenergic alpha-1 Receptor Antagonists/*pharmacology ; Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; Carbazoles/*pharmacology ; Carbon Tetrachloride ; Collagen Type I/drug effects/metabolism ; Cricetinae ; Doxazosin/*pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/blood/chemically induced/*drug therapy ; Liver Function Tests ; Propanolamines/*pharmacology ; Serum Albumin/analysis ; Transforming Growth Factor beta/blood/*drug effects

Epignathus is a rare congenital orofacial teratoma that arises from the sphenoid region of the palate or the pharynx. It occurs in approximately 1:35,000 to 1:200,000 live births representing 2% to 9% of all teratomas. We present the case of a newborn of 39.4 weeks of gestation with a tumor that occupied the entire oral cavity. The patient was delivered by cesarean section. Oral resection was managed by pediatric surgery. Plastic surgery used virtual 3-dimensional models to establish the extension, and depth of the tumor. Bloc resection and reconstruction of the epignathus were performed. The mass was diagnosed as a mature teratoma associated with cleft lip and palate, nasoethmoidal meningocele that conditions hypertelorism, and a pseudomacrostoma. Tridimensional technology was applied to plan the surgical intervention. It contributed to a better understanding of the relationships between the tumor and the adjacent structures. This optimized the surgical approach and outcome.

Background: Necrotizing enterocolitis (NEC) is a severe inflammatory bowel disease in neonates. Our group has developed an experimental model of NEC, with an effectiveness of 73%. Cannabidiol (CBD) is an innovative treatment for neonatal cerebral hypoxic-ischemic pathologies due to its neuroprotective effect, as a potent anti-inflammatory and reducing oxidative stress substance. Our aim was to evaluate the effect of CBD on intestinal lesions in an experimental model of NEC. Results: Mortality and intestinal histological damage was significantly lower in the CBD group compared to the rest (p<0.05), establishing CBD as a protective factor against the development of NEC (OR=0.0255; 95% CI=0.0015-0.4460).At IHQ level (TUNEL technique), a lower cell death rate was also observed in the CBD group compared to the VEH group (p<0.05). Conclusions In our experimental model, intraperitoneal CBD acts as a protective factor against NEC, resulting in less histological damage and a lower rate of intestinal cell death.

Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.
Adipose Tissue, Beige ; metabolism ; pathology ; Adipose Tissue, Brown ; metabolism ; pathology ; Animals ; Cell Line ; Energy Metabolism ; Humans ; Mice ; Obesity ; metabolism ; pathology ; therapy

BACKGROUND/OBJECTIVES: Considering the high number of deaths from coronavirus disease 2019 (COVID-19) in Latin American countries, together with multiple factors that increase the prevalence of vitamin D deficiency, we aimed to determine 25-hydroxyvitamin D (25[OH]D) levels and its association with mortality in patients with critical COVID-19. SUBJECTS/METHODS: This was a prospective observational study including adult patients with critical COVID-19. Data, including clinical characteristics and 25(OH)D levels measured at the time of intensive care unit admission, were collected. All patients were followed until hospital discharge or in-hospital death. The patients were divided into those surviving and deceased patient groups, and univariate and multivariate logistic regression analyses were performed to determine independent predictors of in hospital mortality. RESULTS: The entire cohort comprised 94 patients with critical COVID-19 (males, 59.6%;median age, 61.5 years). The median 25(OH)D level was 12.7 ng/mL, and 15 (16%) and 79 (84%) patients had vitamin D insufficiency and vitamin D deficiency, respectively. The median serum 25(OH)D level was significantly lower in deceased patients compared with surviving (12.1 vs. 18.7 ng/mL, P < 0.001). Vitamin D deficiency was present in 100% of the deceased patients. Multivariate logistic regression analysis revealed that age, body mass index, other risk factors, and 25(OH)D level were independent predictors of mortality. CONCLUSIONS Vitamin D deficiency was present in 84% of critical COVID-19 patients. Serum 25(OH)D was independently associated with mortality in critical patients with COVID-19.