Influence of point mutations on PR65 conformational adaptability: Insights from molecular simulations and nanoaperture optical tweezers.

PR65 is the HEAT repeat scaffold subunit of the heterotrimeric protein phosphatase 2A (PP2A) and an archetypal tandem repeat protein. Its conformational mechanics plays a crucial role in PP2A function by opening/closing substrate binding/catalysis interface. Using in silico saturation mutagenesis, we identified PR65 "hinge" residues whose substitutions could alter its conformational adaptability and thereby PP2A function, and selected six mutations that were verified to be expressed and soluble. Molecular simulations and nanoaperture optical tweezers revealed consistent results on the specific effects of the mutations on the structure and dynamics of PR65. Two mutants observed in simulations to stabilize extended/open conformations exhibited higher corner frequencies and lower translational scattering in experiments, indicating a shift toward extended conformations, whereas another displayed the opposite features, confirmed by both simulations and experiments. The study highlights the power of single-molecule nanoaperture-based tweezers integrated with in silico approaches for exploring the effect of mutations on protein structure and dynamics.

Non-gravid uterine torsion associated with small bowel obstruction.

Uterine torsion is a rare condition. Even more so in cases of non-gravid torsion. We present the case of a post-menopausal woman in her 70s who arrived to our emergency department acutely unwell with abdominal pain and vomiting on a background of a large leiomyomatous uterus, complicated by aspiration pneumonia, acute anaemia, and acute kidney injury. Computed tomography demonstrated a small bowel obstruction secondary to a large heterogeneous calcified pelvic mass. Laparotomy performed demonstrated a large leimyomatous uterus that had torted on the cervical pedicle associated with perforation of the lower anterior segment. A short segment of healthy jejunum was adhered to the uterine fundus, which was easily mobilized. Total hysterectomy and bilateral oophorectomy was performed. The patient made a full recovery. Histopathology demonstrated a calcified leiomyomatous uterus with adjacent haemorrhagic infarction of the uterine wall.

Influence of Point Mutations on PR65 Conformational Adaptability: Insights from Nanoaperture Optical Tweezer Experiments and Molecular Simulations.

PR65 is the HEAT-repeat scaffold subunit of the heterotrimeric protein phosphatase 2A (PP2A) and an archetypal tandem-repeat protein, forming a spring-like architecture. PR65 conformational mechanics play a crucial role in PP2A function by opening/closing the substrate-binding/catalysis interface. Using in-silico saturation mutagenesis we identified "hinge" residues of PR65, whose substitutions are predicted to restrict its conformational adaptability and thereby disrupt PP2A function. Molecular simulations revealed that a subset of hinge mutations stabilized the extended/open conformation, whereas another had the opposite effect. By trapping in nanoaperture optical tweezer, we characterized PR65 motion and showed that the former mutants exhibited higher corner frequencies and lower translational scattering, indicating a shift towards extended conformations, whereas the latter showed the opposite behavior. Thus, experiments confirm the conformations predicted computationally. The study highlights the utility of nanoaperture-based tweezers for exploring structure and dynamics, and the power of integrating this single-molecule method with in silico approaches.

Self-induced back-action for aperture trapping: Bethe-Rayleigh theory.

A dielectric (nano)particle can influence the local electromagnetic field and thereby alter its interaction with that field through the process of self-induced back-action. While this phenomenon is usually considered theoretically as a change in a cavity resonance frequency, such theoretical approaches are not as appropriate when considering systems away from resonance, such as with a subwavelength aperture in a metal film. Here we consider the interaction between an aperture, modelled with Bethe theory as a magnetic dipole, and a Rayleigh particle, modelled as an electric dipole. Using this magnetic dipole - electric dipole interaction, we quantify the self-induced back-action of the particle on the aperture transmission and the optical trapping potential. The model shows quantitative agreement with finite-difference time-domain simulations. This shows that the physics of self-induced back-action for an aperture and a nanoparticle can be understood in terms of dipole-dipole coupling.

Percutaneous edge-to-edge mitral valve repair for symptomatic high surgical risk patients with significant mitral regurgitation - Short term and one year follow up results from a single center in India.

This series reports the safety and feasibility of MitraClip (Abbott Vascular) in 7 high surgical risk Indian patients with symptomatic mitral regurgitation (MR). The clip was deployed successfully in all patients, and more than one clip was required in 5. All had reduction in MR to ≤2+. Mean mitral valve gradient was 3.0 ± 0.8 mmHg. At 12 months follow up, all were alive, and the MR grade was 1+ in 6 patients and 2+ in one. Mean MV gradient was 3.4 ± 1.0 mmHg. The modified Kansas City Quality of life (KCQ) analysis revealed significant improvement in their quality of life (p < 0.0001).

Mitral valve repair in an octogenarian with symptomatic severe mitral regurgitation: First use of MitraClip in India.

Percutaneous mitral valve repair is an accepted treatment of choice in Europe and North America for severe primary or secondary mitral regurgitation, in highly symptomatic patients for whom surgical repair is prohibitively high risk. We describe the first use of the MitraClip in India in a frail elderly female with symptomatic heart failure from severe primary mitral regurgitation who was considered high risk for surgical repair. She had substantial improvement in her symptoms as well as quality of life following the procedure.

Colloidal lithography double-nanohole optical trapping of nanoparticles and proteins.

Double-nanoholes fabricated by colloidal lithography were used for trapping single colloidal particles and single proteins. A gap separation of 60 nm between the cusps of the double-nanohole was achieved in a gold film of 70 nm thickness sputter coated onglass. The cusp separation was reduced steadily down to 10 nm by plasma etching the colloidal particles prior to sputter coating. Scanning electron microscopy was used to locate a particular double-nanohole and it was registered for later microscopy experiments. 30 nm polystyrene particles, the rubisco protein and bovine serum albumin were trapped using a laser focused through the aperture. Compared to other methods that require top-down nanofabrication, this approach is inexpensive and produces high-quality samples.

Transcatheter aortic valve replacement in India-Early experience, challenges, and outcomes from a single center.

BACKGROUND: Despite the increasing popularity of transcatheter aortic valve replacement (TAVR), only about 10,000 TAVR cases have been performed in Asia to date. The procedure is still in a nascent stage in India with very few centers offering this state-of-art technique. Here, we present the early results of TAVR experience at our center. METHODS: Forty-nine patients with severe symptomatic aortic stenosis (AS) were referred to our center for TAVR from November 2015 to February 2018. Twenty-five patients underwent TAVR at our conventional cardiac catheterization laboratory under local or general anesthesia, with standby surgical team support. RESULTS: The mean age of the patients was 72.0 ± 8.1 years. The mean Society of Thoracic Surgeons score was 13.8 ± 10.2. Baseline mean ejection fraction was 50.3 ± 14.8%. Baseline mean aortic valve gradient was 55.8 ± 24.7 mmHg. There was one procedural-related death. Two of the patients required urgent surgery: one for contained annular rupture and one underwent vascular repair for femoral artery occlusion. Mild and moderate paravalvular leak was seen in 11 and 3 patients, respectively. Four patients (16%) required permanent pacemaker. Eighty percent were in New York Heart Association class I-II at discharge. One-year all-cause mortality was 8%, with no hospitalizations or major adverse cardiac event during the 1-year follow-up. CONCLUSION: Our early data clearly shows that in our country, TAVR is a good alternative for symptomatic severe AS for high surgical risk cases. Large-scale multicenter studies are required to study the real impact of TAVR in the Indian scenario. During initial years of implementation of a nationwide TAVR program, it may be prudent to focus on creating TAVR Centers of Excellence by developing an ideal hub and spokes model.

Current practices of Asia-Pacific cardiologists in the utilization of bioresorbable scaffolds.

BACKGROUND & AIMS: Although Absorb Bioresorbable Vascular Scaffolds (A-BVS) are routinely used in the Asia-Pacific, there is little information on patient selection or deployment technique here. This document investigates the experiences of leading interventional cardiologists from the Asia-Pacific region with a focus on patient characteristics, deployment techniques and management. METHODS AND RESULTS: A detailed questionnaire was distributed to 28 highly-experienced interventional cardiologists ('Authors') from 13 Asia-Pacific countries. The results were discussed at a meeting on patient selection, technical consideration, deployment practices and patient management. Potential patient benefits of Absorb compared to metallic DES, the learning curve for patient selection and preparation, device deployment, and subsequent patient management approaches are presented. CONCLUSIONS: Current practices are derived from guidelines optimized for European patients. Differences in approach exist in the Asia-Pacific context, including limited access to imaging and frequency of occurrence of complex lesions. Nevertheless, the use of the Absorb BVS ('Absorb') in certain Asia-Pacific countries has flourished and practices here are continuing to mature.

Prevalence of parameters of suboptimal scaffold deployment following angiographic guided bioresorbable vascular scaffold implantation in real world practice - an optical coherence tomography analysis.

AIM: To assess the prevalence of suboptimal bioresorbable vascular scaffold (BVS, Abbott Vascular, Santa Clara, California) deployment in real world practice with intracoronary optical coherence tomography (OCT) imaging. METHODS: Consecutive patients who underwent percutaneous coronary intervention using BVS and the final optimization assessed with OCT imaging in two tertiary care centers between December 2012 and February 2015 were evaluated for parameters of suboptimal scaffold deployment by OCT. RESULTS: Overall, 36 scaffolds were implanted in 27 patients during this period. Mean age of the population was 54.7±8.2years and 19 (70.4%) were type B2/C lesions. The prevalence of parameters of suboptimal scaffold deployment were: underexpansion-22(61.1%), geographic miss-3(8.3%), tissue prolapse-7(25.9%), scaffold pattern irregularity-1(2.8%), longitudinal elongation-7(38.8%). Of the 7 overlaps imaged: excessive overlap was observed in 3 and scaffold gap in one. The median duration of follow up was 679days (range 193-963days). There were four events during this period. None were associated with suboptimal scaffold deployment. CONCLUSION: OCT based parameters of suboptimal scaffold deployment are common in real world scenario and were not associated with adverse outcomes on long term follow up. These findings need to be confirmed in larger studies.

Alcohol septal ablation for hypertrophic obstructive cardiomyopathy - 8 years follow up.

BACKGROUND: Alcohol septal ablation is emerging as an alternative to surgical myectomy in the management of symptomatic cases of Hypertrophic obstructive cardiomyopathy (HOCM). This involves injection of absolute alcohol into 1st septal perforator thereby producing myocardial necrosis with resultant septal remodelling within 3-6 months. This results in reduction of septal thickness and LV outflow gradients with improvement in symptoms. METHODS: Fifty three patients had undergone alcohol septal ablation, there were 2 early and 2 late deaths and 4 patients lost to follow up. Forty-five (85%) of them were followed up to a mean period of 96 ± 9.2 months. Clinical, ECG, and Echocardiographic parameters were evaluated during follow up. RESULTS: Only 4 out of 51 patients remained in NYHA class III or IV at the end of 6 months. Significant reduction of LV outflow gradients (79 ± 35 to 34 ± 23 mmHg) and septal thickness (23 ± 4.7 mm to 19 ± 3 mm) were observed during 6 months follow up. Beyond 6 months there was no further decrease in either septal thickness or LVOT gradients noted. Ten percent of patients needed pacemaker implantation. There was 92% survival at the end of 8 years. CONCLUSION: Alcohol septal ablation is a safe and effective nonsurgical procedure for the treatment of HOCM. By minimizing the amount of alcohol to ≤ 2 ml, one can reduce complications and mortality. The long-term survival is gratifying.

Vibrational spectroscopic studies and computational calculations of 5-chloro-2-(3-chlorophenylcarbamoyl)phenylacetate.

The FT-IR and FT-Raman spectra of 5-chloro-2-(3-chlorophenylcarbamoyl)phenylacetate were studied. The vibrational wave numbers and corresponding vibrational assignments were examined theoretically using the Gaussian 03 set of quantum chemistry codes and the normal modes are assigned by Potential Energy Distribution calculations. The synthesis, elemental analysis and NMR values are presented. The red shift of the NH stretching wave number in the infrared spectrum from the computed wave number indicates the weakening of the NH bond resulting in proton transfer to the neighboring oxygen atom. The first hyperpolarizability, infrared intensities and Raman activities are reported. The calculated first hyperpolarizability is comparable with the reported values of similar derivatives and is an attractive object for future studies of nonlinear optics. The geometrical parameters of the title compound are in agreement with that of similar reported derivatives.

Secondary injury potential of assistive technologies used by farmers with disabilities: findings from case studies.

In order to complete essential tasks, farmers with disabilities often make and use assistive technology (AT), which itself may cause further injuries known as secondary injuries. A set of 19 case studies was used to investigate the potential for injury on home-fabricated assistive technologies (ATs) used by farmers with disabilities. The case studies consisted of close-ended and open-ended interviews that were designed to help understand the farmers' perception of potential for injuries and safety measures implemented or not implemented. The qualitative study used grounded theory principles and the collected data were analyzed to arrive at a list of features on ATs that have substantial potential to cause injury to the user. Based on the case study results, AT user characteristics and environmental factors were also considered as factors that contribute to potential injuries. Findings were used to develop an instrument for use by rehabilitation professionals to evaluate ATs for potential injury causing hazards.

FT-IR, FT-Raman and DFT calculations of 4-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl acetate.

FT-IR and FT-Raman spectra of 4-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl acetate were recorded and analyzed. Synthesis and elemental analysis are also reported. The vibrational wavenumbers of the compound have been computed on the basis of density functional theory using B3LYP/6-31G* basis set. The predicted infrared intensities and Raman activities are reported.

Differentiation of saraca asoca crude drug from its adulterant.

Saraca asoca commonly known as asoka, which is considered as a sacred tree by Hindus and Buddhists possesses various medicinal uses. The stem bark of the tree is the principal constituent of several ayurvedic preparations which are widely prescribed in leucorrhoea, haematuria, menorrhagia and other diseases of the female genitourinary system. Because of destructive extraction and the absence of an organized cultivation programme, the avilbility of the crude drug is diminishing and this has resulted in the sale of adulterants. The commonly used adulterant is the bark of Polyalthia longifolia which shows some similarity with that of asoka. Studies were conducted at Aromatic and Medicinal Plants Research station, Odakkali (Kerala Agricultural University) during 2001-2002 to evolve methods for differentiating the original drug from the adulterant species by anatomical biochemical and chromatographic techniques.