Characterization of miRNAs modulated by torpor in the hibernating ground squirrel Ictidomys tridecemlineatus liver by next-generation sequencing.

BACKGROUND: Mammalian hibernation is a fascinating phenomenon that involves multiple molecular and biochemical changes to proceed. While the molecular picture associated with torpor has become clearer in recent years, the function of non-coding RNAs, and especially of microRNAs, solicited during this process is not well understood. OBJECTIVE: To better characterize a signature of cold torpor-associated miRNAs in the hibernating thirteen-lined ground squirrel Ictidomys tridecemlineatus. MATERIALS AND METHODS: Next-generation sequencing and qRT-PCR approaches were conducted in euthermic and hibernating ground squirrel liver tissues. RESULTS: This high-throughput approach notably revealed modulation during hibernation of various miRNAs previously associated with lipid metabolism, glucose metabolism and antioxidant responses such as miR-145a-3p, miR-22-3p and miR-25-3p, respectively. CONCLUSION: Overall, these results present a group of miRNAs differentially expressed in hibernating ground squirrel liver and provide additional knowledge on the underlying functions of these small non-coding molecules during cold torpor.

Predicting discharge destination with admission outcome scores in stroke patients.

BACKGROUND: The goal of this study was to predict the discharge location for stroke patients. OBJECTIVE: To design a tool to assess a community discharge that will assist in development of individualized care plans and discharge planning. METHODS: Patients (N = 407) hospitalized for an acute stroke in an inpatient rehabilitation facility were used for this retrospective study. Admission data from the Functional Independence Measure (FIM) and Simplified Stroke Rehabilitation Assessment of Movement (S-STREAM) were used to determine predictive factors for a community discharge. RESULTS: Logistic regressions and chi-square analyses were used to determine admission factors that predict a community discharge and the cut off score for each predictive variable. The S-STREAM, Motor FIM, Total FIM, FIM Bladder, FIM bed transfer, FIM toilet transfer, FIM bathing, and FIM memory were predictive of a community discharge. A predictive tool with a sensitivity and specificity of 76% and 64% was developed using the combined relative risk scores of the S-Stream, FIM Bladder, FIM Bed Transfer and FIM Memory. CONCLUSIONS: By using outcome data at the time of admission, a discharge destination can be predicted for stroke patients with significant sensitivity and specificity.

Mammalian hibernation and regulation of lipid metabolism: a focus on non-coding RNAs.

Numerous species will confront severe environmental conditions by undergoing significant metabolic rate reduction. Mammalian hibernation is one such natural model of hypometabolism. Hibernators experience considerable physiological, metabolic, and molecular changes to survive the harsh challenges associated with winter. Whether as fuel source or as key signaling molecules, lipids are of primary importance for a successful bout of hibernation and their careful regulation throughout this process is essential. In recent years, a plethora of non-coding RNAs has emerged as potential regulators of targets implicated in lipid metabolism in diverse models. In this review, we introduce the general characteristics associated with mammalian hibernation, present the importance of lipid metabolism prior to and during hibernation, as well as discuss the potential relevance of non-coding RNAs such as miRNAs and lncRNAs during this process.

Studies in serum support rapid formation of disulfide bond between unpaired cysteine residues in the VH domain of an immunoglobulin G1 molecule.

Recombinant monoclonal antibodies undergo extensive posttranslational modifications. In this article, we characterize major modifications, separated by cation exchange chromatography, on an immunoglobulin G1 (IgG1) monoclonal antibody (mAb). We found that N-terminal cyclization of glutamine residues to pyroglutamate on the light and heavy chains are the major isoforms resolved during cation exchange chromatography. However, using CEX, we also separated and identified isoforms with unpaired cysteine residues in the V(H) domain of the molecule (Cys22-Cys96). Omalizumab, a therapeutic anti-IgE antibody, has unpaired cysteine residues in the V(H) domain between Cys22 and Cys96, and the Fab fragment, containing the unpaired cysteine residues, is reported to have reduced potency. Dynamic interchain disulfide rearrangement, with slow kinetics, was recently reported to take place in serum for an IgG2 molecule and resulted in predictable mature isoforms. Analytical evaluation of our mAb, after recovery from serum, revealed that the unpaired intrachain cysteine residues (Cys22-Cys96) reformed their disulfide bond. The significance of this study is that correct pairing occurred rapidly, and we speculate that thiol molecules such as cysteine, homocysteine, and glutathione in serum provide an environment, outside the endoplasmic reticulum, for correct linkage.

Selection of specific endophytic bacterial genotypes by plants in response to soil contamination.

Plant-bacterial combinations can increase contaminant degradation in the rhizosphere, but the role played by indigenous root-associated bacteria during plant growth in contaminated soils is unclear. The purpose of this study was to determine if plants had the ability to selectively enhance the prevalence of endophytes containing pollutant catabolic genes in unrelated environments contaminated with different pollutants. At petroleum hydrocarbon contaminated sites, two genes encoding hydrocarbon degradation, alkane monooxygenase (alkB) and naphthalene dioxygenase (ndoB), were two and four times more prevalent in bacteria extracted from the root interior (endophytic) than from the bulk soil and sediment, respectively. In field sites contaminated with nitroaromatics, two genes encoding nitrotoluene degradation, 2-nitrotoluene reductase (ntdAa) and nitrotoluene monooxygenase (ntnM), were 7 to 14 times more prevalent in endophytic bacteria. The addition of petroleum to sediment doubled the prevalence of ndoB-positive endophytes in Scirpus pungens, indicating that the numbers of endophytes containing catabolic genotypes were dependent on the presence and concentration of contaminants. Similarly, the numbers of alkB- or ndoB-positive endophytes in Festuca arundinacea were correlated with the concentration of creosote in the soil but not with the numbers of alkB- or ndoB-positive bacteria in the bulk soil. Our results indicate that the enrichment of catabolic genotypes in the root interior is both plant and contaminant dependent.

Open antireflux repairs for simple reflux esophagitis: short- and long-term results.

This analysis of the results of open antireflux surgery clearly shows a benefit for antireflux surgery in most patients who have severe esophagitis with or without hiatal hernia. The authors of this article have found many variations in the methodology used to evaluate these results. Aside from these problems, however, the authors also have noticed the remarkably serious and honest work performed by most surgeons in trying to report the truth with the methodologies available to them. The principles of antireflux surgery can be found among the different studies that are reviewed in this article. These principles include: 1. The necessity of closing the crura; 2. The importance of repositioning the distal esophagus into the abdominal cavity; 3. The necessity of increasing the LES pressure by using the musculature of the fundus; 4. The preference for using a short and floppy fundoplication to avoid side effects; and 5. The need for long-term follow-up in evaluating results.

D4 dopamine receptor-mediated phospholipid methylation and its implications for mental illnesses such as schizophrenia.

Previous studies have shown D2-like dopamine receptor involvement in the regulation of phospholipid methylation (PLM), while others have documented impaired methionine and folate metabolism in schizophrenia. Utilizing [14C]formate labeling in cultured neuroblastoma cell lines, we now show that D4 dopamine receptors (D4R) mediate the stimulatory effect of dopamine (DA) on PLM. The effect of DA was potently blocked by highly D4R-selective antagonists and stimulated by the D4R-selective agonist CP-226269. DA-stimulated PLM was dependent upon the activity of methionine cycle enzymes, but DA failed to increase PLM in [3H]methionine labeling studies, indicating that a methionine residue in the D4R might be involved in mediating PLM. A direct role for MET313, located on transmembrane helix No. 6 immediately adjacent to phospholipid headgroups, was further suggested from adenosylation, site-directed mutagenesis and GTP-binding results. A comparison of PLM in lymphocytes from schizophrenia patients vs control samples showed a four-fold lower activity in the schizophrenia group. These findings reveal a novel mechanism by which the D4R can regulate membrane composition. Abnormalities in D4R-mediated PLM may be important in psychiatric illnesses such as schizophrenia.

Lung cancer in women compared with men: stage, treatment, and survival.

BACKGROUND: In cardiac disease there appears to be a difference in the treatment of men and women, and thus an advantage in survival in men. This study aimed to determine whether these differences exist in lung cancer. METHODS: We undertook a retrospective cohort study in a university hospital. The study population consisted of 104 consecutive women and 104 consecutive men with newly diagnosed lung cancer between March 1988 and June 1990. The following information was collected: sex, age, presenting symptoms, investigations, histology, stage, treatment, and survival. RESULTS: The location of the tumor, presenting symptoms, investigations, and stages were similar in men and women. There was a difference in the distribution of the various histologic types of lung cancer: Small cell lung cancer was more frequent in women (25% versus 11.5% in men) and squamous cell carcinoma more frequent in men (38% in women versus 51% in men). The overall survival was similar among the two sexes, but there was a survival advantage in women when adjusted for stage. CONCLUSIONS: There was a higher incidence of small cell carcinoma in women and squamous cell carcinoma in men. There was evidence of a difference in the survival rate of lung cancer in favor of women according to stage.

Bowel preparation with polyethylene glycol electrolyte lavage solution is potentially hazardous in patients with carcinoma of the cardia: a case report.

Polyethylene glycol (PEG) electrolyte solution can induce potentially fatal complications when used as a lavage in preoperative bowel preparation. A 60-year-old man with carcinoma of the esophagogastric junction had a Mallory-Weiss tear after bowel preparation with PEG. He was successfully resuscitated, first with balanced salt solution then by transfusion. The literature on the subject is reviewed and recommendations are made, which include consideration of alternative methods of bowel preparation (e.g., sodium phosphate solution) in patients with esophageal obstruction.

[Endoscopic YAG laser and palliative therapy of cancer of the esophagus]. / Le laser YAG endoscopique et la thérapie palliative du cancer de l'oesophage.

In our institution, the YAG laser has been used to treat 110 patients with inoperable esophageal carcinoma. Therapy was palliative as patients presented metastases (41.8%), advanced systemic disease (22.7%), extensive local disease (18.2%) or recurrent carcinoma (10%). The study group included 92 men (mean age 68.4 years) and 18 women (mean age 67.0 years); 47.3% of the patients had received no previous treatment while 52.7% had been treated previously with either radiotherapy, chemotherapy, surgery, stents or dilatation. The majority of lesions were adenocarcinomas (57.3%) with squamous cell carcinomas in 37.3%; 66.3% of cancers were located in the distal third of the esophagus. The patients received a mean of 2.4 laser treatments with 4883 joules per treatment on average. The rate of major complications was 2.7% and the rate of mortality 1.8%. The median survival for the group was 4.5 months. No significant difference was found in the length of survival according to the histology of the tumour (p = 0.35), the presence of metastases (p = 0.24) and the association of other treatment modalities with the laser (p = 0.06). Functional results were considered good to excellent in 82.1% of cases. In conclusion, the YAG laser does not influence overall survival of inoperable patients, but this therapy is effective and safe and is presently the treatment of choice for these patients.

Serum angiotensin-converting enzyme level is elevated in patients with human immunodeficiency virus infection.

BACKGROUND: Serum angiotensin-converting enzyme (ACE) level is elevated in a number of disease states and medical conditions. Based on review of the medical literature, we postulated that serum ACE level elevation may occur during infection with the human immunodeficiency virus (HIV). METHODS: In a prospective, controlled study, serum ACE levels of HIV-positive patients were compared with those of an HIV-negative control population. RESULTS: Serum ACE levels were significantly elevated in patients with the acquired immunodeficiency syndrome (55.4 +/- 11.4 U/L) and in patients with an intermediate stage of HIV infection (57.2 +/- 25.3 U/L) when compared with levels in controls (31.9 +/- 14.0 U/L). CONCLUSIONS: Elevated serum ACE levels occur in HIV infection and may be an important marker for this disease.

Unsuspected metastatic choriocarcinoma presenting as unilateral spontaneous pneumothorax.

Spontaneous pneumothoraces are usually caused by subpleural apical blebs but may also be secondary to metastasis to the lung. We present the case of a 20-year-old woman with spontaneous pneumothorax secondary to choriocarcinoma metastatic to the lung.