Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase

Research in recent decades has revealed that the guanine (G)-quadruplex secondary structure in DNA modulates a variety of cellular events that are mostly related to serious diseases. Systems capable of regulating DNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. A high specificity for recognition of telomeric G-quadruplex has been observed for BLM helicase. We identified peptides from the HRDC domain of BLM using a molecular docking approach with various available solutions and crystal structures of human telomeres and recently created a peptide library. Herein, we tested one peptide (BLM HRDC peptide) from the library and examined its interaction with human telomeric variant-1 (HTPu-var-1) to understand the basis of G4-protein interactions. Our circular dichroism (CD) data showed that HTPu-var-1 folded into an anti-parallel G-quadruplex, and the CD intensity significantly decreased upon increasing the peptide concentration. There was a significant decrease in hypochromicity due to the formation of G-quadruplex-peptide complex at 295 nm, which indicated the unfolding of structure due to the decrease in stacking interactions. The fluorescence data showed quenching upon titrating the peptide with HTPu-var-1-G4. Electrophoretic mobility shift assay confirmed the unfolding of the G4 structure. Cell viability was significantly reduced in the presence of the BLM peptide, with IC₅₀ values of 10.71 μM and 11.83 μM after 72 and 96 hours, respectively. These results confirmed that the selected peptide has the ability to bind to human telomeric G-quadruplex and unfold it. This is the first report in which a peptide was identified from the HRDC domain of the BLM G4-binding protein for the exploration of the G4-binding motif, which suggests a novel strategy to target G4 using natural key peptide segments.

Schematic representation of (HTPu–var-1-G4) located at the 3′ end, formation of G-quadruplex, model of the G-quadruplex structure, base stacking between G-quadruplex planes, G-quadruplex structure-peptide complex and twisting of G-quadruplex planes upon peptide binding.     

Measurement of ventricular size in term and preterm infants.

Real time ultrasonography was done in neonates to establish the norms for ventricular size and to see if there is a correlation between ventricle size and gestational age. A total of 153 normal infants admitted to our nursery after September, 1989 were taken up for the study. First ultrasound was performed within six days of birth. Sonography was done with 3.5 MHz transducer through anterior and lateral fontanelle. Results revealed that there is a significant difference in the mean value of falx to lateral wall of the cortex, ventricular index and ratio (VI/FC) of preterm and term infants. The ventricular size of small for gestational age infants is significantly different from appropriate gestational age infant of corresponding gestational ages. The percentile chart of VI for Indian infants is comparable to that of western infants.     

Outcomes for patients with infantile idiopathic scoliosis by casting table type

Purpose:Serial casting is an effective treatment for infantile idiopathic scoliosis. The most common casting table types are Mehta, Risser, and spica tables. We compared major curve correction between patients with infantile idiopathic scoliosis treated using pediatric hip spica tables versus Risser or Mehta tables.Methods:In this multicenter retrospective study, we included 52 children younger than 3 years (mean ± standard deviation age, 1.6 ± 0.68 years) treated with ≥2 consecutive casts for infantile idiopathic scoliosis between September 2011 and July 2018. We compared major curve angle (measured using the Cobb method) before and after treatment and improvement in curve angle between the spica tables group (n = 12) and the Risser or Mehta tables group (n = 40). The primary outcome was the difference in percentage correction of the major curve according to radiographs taken after first casting and at final follow-up.Results:The mean major curve was 47° ± 18° before casting. A median of six casts (range: 2–14) were applied. Mean follow-up after treatment initiation was 22 months (range: 7–86 months). At baseline, the major curve was significantly larger in the spica tables group (58°) than in the Risser or Mehta tables group (43°) (p = 0.01). We found no differences in the percentage curve correction in the spica tables group versus Risser or Mehta tables group after first casting or at final follow-up.Conclusion:Serial casting was associated with substantial major curve correction in patients with infantile idiopathic scoliosis. Curve correction did not differ between patients treated with a spica table versus a Risser or Mehta table.Level of Evidence:Level III, retrospective cohort study     

Full-thickness and partial-thickness supraspinatus tendon tears: value of US signs in diagnosis

PURPOSE: To determine which US signs are important in the diagnosis of a surgically identifiable supraspinatus tendon tear. MATERIALS AND METHODS: Fifty consecutive ultrasonographic (US) studies of the shoulder in patients who underwent arthroscopic follow-up were retrospectively reviewed by a musculoskeletal radiologist. US images of the supraspinatus tendon were evaluated for tendon nonvisualization, abnormal tendon echogenicity, tendon thinning, greater tuberosity cortical irregularity, cartilage interface sign, joint fluid, and subacromial-subdeltoid bursal fluid. US findings were compared with arthroscopic results. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each US sign in the diagnosis of full-thickness tendon tear and again for any type of supraspinatus tendon tear. RESULTS: Arthroscopy revealed 21 full-thickness tears, five bursal surface partial-thickness tears, 10 articular surface partial-thickness tears, and 14 patients without tear of the supraspinatus tendon. The presence of greater tuberosity cortical irregularity and joint fluid was most important in the diagnosis of full-thickness supraspinatus tendon tear (sensitivity, 60%; specificity, 100%; positive predictive value, 100%; negative predictive value, 78%; accuracy, 84%). For diagnosis of any type of supraspinatus tendon tear (partial or full thickness), tendon nonvisualization, greater tuberosity cortical irregularity, and cartilage interface sign are most important, although a combination of signs did not improve accuracy. CONCLUSION: Secondary US signs, such as greater tuberosity cortical irregularity and joint fluid, are most valuable in the diagnosis of supraspinatus tendon tear.     

Diffusion tensor tractography demonstration of partially injured spinal cord tracts in a patient with posttraumatic Brown Sequard syndrome

The authors report the utility of diffusion tensor tractography in demonstrating the partially severed spinal cord tracts on one side with normal, intact, distally traceable tracts on the opposite side in a patient with posttraumatic Brown Sequard syndrome. A 30-year-old man presented with typical clinical features of a hemisection injury of the thoracic spinal cord, 2 months after he had sustained a back stab injury. Routine MRI showed T2 hyperintense zones in the thoracic spinal cord at the level of T5. We did axial single shot echo planar diffusion tensor imaging with a 1.5 Tesla MR machine. Tractography effectively depicted the injured spinal cord tracts on the left side with normal intact tracts on the right side, which could be traced distally. The fractional anisotropy and apparent diffusion coefficient values showed significant changes at the level of injury. Tractographic demonstration of human spinal cord injury is reported for the first time.     

Liver profile in COVID-19: a meta-analysis

Journal of Public Health - Few studies have been performed to investigate multiorgan failure occurring with extrapulmonary symptoms like diarrhea, anorexia, and vomiting. There has been no attempt...     

Dimethyl sulfoxide with lignocaine versus eutectic mixture of local anesthetics: prospective randomized study to compare the efficacy of cutaneous anesthesia in shock wave lithotripsy

The objective of the study was to compare the efficacy of dimethyl sulfoxide (DMSO) mixed with lignocaine and eutectic mixture of local anesthetics (EMLA) cream as topically applied surface anesthetics in relieving pain during shock wave lithotripsy (SWL) in a prospective randomized study. Of the 160 patients, 80 patients received DMSO with lignocaine and 80 patients received EMLA cream, applied to the skin of the flank at the area of entry of shock waves. SWL was done with Seimens lithostar multiline lithotripter. The pain during the procedure was assessed using visual analog and verbal rating scores. The mean visual analog scale scores for the two groups were 3.03 for DMSO group and 4.43 for EMLA group. The difference of pain score on visual analog scale was statistically significant (p < 0.05). Similarly, the pain scores as rated on the verbal rating scale were also evaluated; the mean score on verbal rating scale were 2.34 for DMSO group and 3.00 for the EMLA group. The difference between the pain score on verbal rating scale was also found to be statistically significant (p < 0.05). Our study showed that DMSO with lignocaine is a better local anesthetic agent for SWL than EMLA cream. The stone fragmentation and clearance rates are also better in the DMSO group.     

Identification of accessory bile ducts at cholecystectomy

The presence of accessory channels between the liver and extrahepatic bile ducts has long been recognised by anatomists and the division of such ducts may be a cause of bile leakage following cholecystectomy. However, visualisation of accessory bile ducts at operation is difficult as they are often small and sometimes less than 1 mm in diameter. Cholangiography has been used to help in the identification of accessory ducts in 50 patients included in a prospective trial. X-rays were taken after dissection of the gall bladder from its bed and extravasation of contrast was seen on five occasions (10%) suggesting leakage from divided accessory ducts. The identification of damage to accessory bile ducts in 10% of patients suggests that this may occur more frequently than previously supposed.     

Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, Enterodiol, and enterolactone

Secoisolariciresinol diglucoside (SDG), an anti-oxidant isolated from flaxseed, is metabolized to secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) in the body. The effectiveness of SDG in hypercholesterolemic atherosclerosis, diabetes, and endotoxic shock could be due to these metabolites. These metabolites may have antioxidant activity. However, the antioxidant activity of these metabolites is not known. The antioxidant activity of SECO, ED, and EL was investigated using chemiluminescence (CL) of zymosan-activated polymorphonuclear leukocytes (PMNLs) [PMNL-CL]. Other antioxidants (SDG and vitamin E) were also used for comparison. SDG, SECO, ED, EL, and vitamin E, each in the concentration of 0.5, 1.0, 2.5, 5.0 and 10.0 mg/ml, produced a concentration-dependent reduction in zymosan-activated PMNL-CL. SDG, SECO, ED, EL, and vitamin E, in the concentration of 2.5 mg/ml, produced a reduction of zymosan-activated PMNL-CL by 23.8%, 91.2%, 94.2%, 81.6% and 18.7%, respectively. Activated PMNLs produce reactive oxygen species and luminol-dependent CL reflects the amount of oxygen species generated from activated PMNLs. The reduction of PMNL-CL, therefore, reflects the antioxidant activity of the compounds studied. These results suggest that the metabolites of SDG have antioxidant activity. The antioxidant activity was highest with SECO and ED and lowest with vitamin E. The antioxidant potency of SECO, ED, EL, and SDG was 4.86, 5.02, 4.35, and 1.27 respectively, as compared to vitamin E. SECO, ED and EL are respectively 3.82, 3.95, and 3.43 more potent than SDG.