Orientation dependence in fluorescent energy transfer between Cy3 and Cy5 terminally attached to double-stranded nucleic acids

We have found that the efficiency of fluorescence resonance energy transfer between Cy3 and Cy5 terminally attached to the 5′ ends of a DNA duplex is significantly affected by the relative orientation of the two fluorophores. The cyanine fluorophores are predominantly stacked on the ends of the helix in the manner of an additional base pair, and thus their relative orientation depends on the length of the helix. Observed fluorescence resonance energy transfer (FRET) efficiency depends on the length of the helix, as well as its helical periodicity. By changing the helical geometry from B form double-stranded DNA to A form hybrid RNA/DNA, a marked phase shift occurs in the modulation of FRET efficiency with helix length. Both curves are well explained by the standard geometry of B and A form helices. The observed modulation for both polymers is less than that calculated for a fully rigid attachment of the fluorophores. However, a model involving lateral mobility of the fluorophores on the ends of the helix explains the observed experimental data. This has been further modified to take account of a minor fraction of unstacked fluorophore observed by fluorescent lifetime measurements. Our data unequivocally establish that Förster transfer obeys the orientation dependence as expected for a dipole–dipole interaction.     

Idiopathic chronic eosinophilic pneumonia: a case report

Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare cause of chronic lung disease in children and adolescents. We described four-years old boy presenting with recurrent pneumonia and symptoms of bronchial asthma. Because of peripheral eosinophilia and bilateral pulmonary infiltrates patient investigated comprehensive and chronic eosinophilic pneumonia determined histopathologically. Other conditions causing eosinophilic pneumonia were ruled out. He showed a dramatic response to oral corticosteroid therapy. This report emphasizes that ICEP should be considered in pediatric age group on a cause for chronic hypoxemi or intractable symptoms of respiratory system.     

The effects of iloprost on ischemia-reperfusion injury in skeletal muscles in a rodent model

Purpose

The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model.

Materials and methods

Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses.

Results

Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL.

Conclusions

These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model.     

Endoscopic Therapy with 2-Octyl-cyanoacrylate for the Treatment of Gastric Varices

Background

Gastric variceal bleeding is associated with significant morbidity and mortality and limited endoscopic therapeutic options.

Aim

The aim of this study was to evaluate the short- and long-term efficacy and safety of endoscopic therapy with 2-octyl-cyanoacrylate in patients with gastric variceal bleeding.

Methods

A single-center retrospective review of patients receiving endoscopic therapy for gastric variceal hemorrhage. Patient demographics, laboratory, and procedural data were collected. Patients were followed to death, liver transplantation, or last follow-up. Success rates were defined as immediate control of bleeding; early re-bleeding (1–7 days), short-term re-bleeding (1–12 weeks), overall survival, and serious procedure complications.

Results

A total of 41 patients (39 with cirrhosis) underwent 54 cyanoacrylate injections during study period. Mean age was 57 and 73 % were males. Twenty-four (58.5 %) patients had failed or were deemed ineligible for transjugular intra-hepatic portosystemic shunt, and 5 % were done for primary prophylaxis. Immediate hemostasis was achieved in five active bleeders. During a median survival time of 117 days, early re-bleeding was seen in 1 (2.4 %), short-term re-bleeding in five patients (12 %), and varices were eradicated in 15 (46.8 %) patients on follow-up. Mean MELD score at the time of the first injection was 17.1 ± 7.8. Mean volume injected was 3.4 cc and median number of varices injected per session was one. Eight patients died during the long-term follow-up: metastatic cancer (2), infections (3), liver failure (1), and re-bleeding (2). There were no serious procedure-related complications.

Conclusions

Endoscopic cyanoacrylate therapy appears effective and safe for treatment of patients with bleeding from gastric varices or high-risk stigmata.     

Venetoclax and hypomethylating agents in FLT3-mutated acute myeloid leukemia

FMS-like tyrosine kinase 3 (FLT3) mutations are prevalent in acute myeloid leukemia (AML), and their presence confers adverse risk. FLT3-mutated (FLT3m) AML is a challenging leukemia to manage, particularly in older and unfit patients as well as patients with relapsed/refractory (r/r) disease. We retrospectively analyzed the outcomes of 50 FLT3m AML patients (17 treatment-naïve, 33 r/r) treated with venetoclax (VEN) and hypomethylating agents (HMA). The overall CR/CRi rate with VEN-HMA was 60% (94% in treatment-naïve AML and 42% in r/r AML). Early (60-days) treatment related mortality was 2%. The r/r AML setting was an independent predictor of lower complete response (OR: 0.08; 95%CI: 0.00-0.60, P = .03). Cytogenetics-molecular risk, concurrent mutations, the type of FLT3 mutation (ITD vs TKD), the ITD allelic ratio, the type of HMA, age, prior exposure to HMA and receipt of prior allogeneic transplant did not independently impact response or leukemia-free survival (LFS). Concurrent IDH mutations were associated with lower CR/CRi (P = .01), while ASXL1 or TET2 mutations showed a non-significant association toward higher CR/CRi (P = .07, for both). However, none of the concurrent mutations were an independent predictor for response when adjusted to AML setting. In conclusion, VEN-HMA is associated with encouraging efficacy in FLT3m AML among both newly diagnosed unfit and r/r patients.     

Malnutrition,associated clinical factors,and depression in systemic sclerosis: a cross-sectional study

Clinical Rheumatology - The aim of this study was to evaluate the associations between malnutrition and the clinical features of the disease and depression in patients with systemic sclerosis...     

An unusual presentation of perforated appendicitis in epigastric region

INTRODUCTION

Atypical presentations of appendix have been reported including backache, left lower quadrant pain and groin pain from a strangulated femoral hernia containing the appendix. We report a case presenting an epigastric pain that was diagnosed after computed tomography as a perforated appendicitis on intestinal malrotation.

PRESENTATION OF CASE

A 27-year-old man was admitted with a three-day history of epigastric pain. Physical examination revealed tenderness and defense on palpation of epigastric region. There was a left subcostal incision with the history of diaphragmatic hernia repair when the patient was 3 days old. He had an intestinal malrotation with the cecum fixed at the epigastric region and the inflamed appendix extending beside the left lobe of liver.

DISCUSSION

While appendicitis is the most common abdominal disease requiring surgical intervention seen in the emergency room setting, intestinal malrotation is relatively uncommon. When patients with asymptomatic undiagnosed gastrointestinal malrotation clinically present with abdominal pain, accurate diagnosis and definitive therapy may be delayed, possibly increasing the risk of morbidity and mortality.

CONCLUSION

Atypical presentations of acute appendicitis should be kept in mind in patients with abdominal pain in emergency room especially in patients with previous childhood operation for diaphragmatic hernia.     

Frequency and Predictors of Non-compliance to Dietary Recommendations Among Hypertensive Patients

Compliance to dietary recommendations among hypertensive people is a major health care issue. Non-compliance can nullify the effects of even the most scientific and optimum treatment plan. The main aim of this study was to determine the frequency and predictors of non-adherence in our region. We also investigated the possible factors based on patient opinions that could increase compliance. A sample of 400 adult patients, diagnosed with hypertension for at least 3 years, who visited Civil Hospital during the time period April–June 2013 were included in this cross sectional study. Patient data and opinions were collected by two trained interviewers using a pre-coded questionnaire. Compliance was assessed based on patients self report. More than three quarters (n = 310, 77.5 %) of the hypertensive patients were non-compliant. More than one social gathering in a week, peer-influence, no friends to follow the recommended diet plan and lack of believe regarding diet as an effective measure to control blood pressure were found to be the significant predictors of non-compliance (P values <0.0001). Counseling was thought to be the most effective way by the patients to increase adherence. Non-compliance to dietary recommendations is a major problem prevalent especially in Pakistan. There is an urgent need for doctors and nurses to counsel their patients effectively to prevent future morbidities and mortalities because of non-compliance.