High incidence of PI3K pathway gene mutations in South Indian cervical cancers.

INTRODUCTION: Cervical cancer is the second most common cancer in India. The phosphatidylinositol-3 kinase (PI3K) signaling is one of the most commonly activated pathways in cancer and comprises key molecules commonly targeted in cancer therapy. This study analyzed six PI3K pathway gene mutations. METHODS: We carried out targeted next-generation sequencing of six PI3K pathway genes (PIK3CA, PIK3R1, PTEN, AKT1, TSC2, and mTOR) in a total of 93 South Indian cervical cancer samples and confirmed them by sanger sequencing. RESULTS: The PI3K pathway gene mutations were observed in 54.8% (51/93) of the tumors and PIK3CA was the most mutated (34.4%, 32/93), followed by TSC2 (18.3%, 17/93), and PIK3R1 (14%, 13/93). The PIK3CA hotspot mutations E542K and E545K observed in this study were likely to disrupt the p110α-p85α interaction that could result in the PI3K pathway activation. We also found a few novel mutations in PIK3R1, PTEN, AKT1, TSC2, and mTOR genes while some of the tumors harbored multiple mutations in the genes of the PI3K pathway. The majority of the tumors were positive for high-risk HPV16/18 (60.7%). CONCLUSIONS: The high incidence of the PI3K pathway gene mutations observed in this study could be exploited for the therapeutic management of cervical cancers.

Facile synthesis of efficient construction of tungsten disulfide/iron cobaltite nanocomposite grown on nickel foam as a battery-type energy material for electrochemical supercapacitors with superior performance.

In this research literature, a tungsten disulfide/iron cobaltite (WS2/FeCo2O4) interwoven construction array was prepared by a simplistic hydrothermal approach on Ni foam as an integrative electrode for supercapacitors (SCs). For characterization of the wearing of WS2 nanostructure on FeCo2O4 nanosheets (WS2/FeCo2O4) by the Scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The WS2/FeCo2O4 nanosheets supply a larger surface region and sufficient space to allow for volume changes. Moreover, considerable features of wellbeing conductivity from the Ni foam conductor and the synergistic procedures between WS2 and FeCo2O4, the integrated WS2/FeCo2O4 composite achieved prominent SCs storage performances with a higher specific capacity of 1122C g-1 (2492.9F g-1) at 1 A g-1 and notable capacity retention of 98.1% at 3 A g-1 after 5000 long cycles and retained higher rate capacity of 951.9 C g-1 at 15 A g-1. For practical application, an asymmetric supercapacitors type WS2/FeCo2O4//active carbon (WS2/FeCo2O4//AC) device was successfully prepared. The WS2/FeCo2O4//AC device displays a higher specific capacity of 110C g-1 and energy density of 85.68 W h kg-1 at power density at 897.65 W kg-1, as well as the superior initial capacitance of 98.7% with cyclic stabilities after 4000 long cycles. Thus, these results indicated the great potential of the constructed WS2/FeCo2O4//AC in the scenario electrochemical properties due to their outstanding energy storage activities.

Speculative assessment, molecular composition, PDOS, topology exploration (ELF, LOL, RDG), ligand-protein interactions, on 5-bromo-3-nitropyridine-2-carbonitrile.

Computational calculations of 5-bromo-3-nitropyridine-2-carbonitrile (5B3N2C) on molecular structure and on energy are implemented using the 6-311++G(d,p) basis set by DFT/B3LYP method. The UV-Vis spectrum of 5B3N2C was obtained by TD-DFT with chloroform as a solvent. The analysis of molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) were used to evaluate, the entire electron density and organic reactive sites of 5B3N2C. The electron-hole conversions were conjointly deliberated. Donor-acceptor interactions (NBO) analysis examines the intra-and intermolecular charge transfer, hyper conjugate interaction of the compound. The orbital molecular contributions are evaluated by density of states (DOS and PDOS). To discern the reactivity of the molecule, topology analyses were done. The biological prominence of the 5B3N2C molecule was investigated in a pertinent study of molecular docking with target protein 3CEJ exhibiting the centromere associated protein inhibitor property. Molecular Dynamics simulations were done to assess the stability of the complex. 5B3N2C physiochemical parameters were also compared to those of widely viable medications Ispinesib and Lonafarnib.

Electrocatalyst based on Ni-MOF intercalated with amino acid-functionalized graphene nanoplatelets for the determination of endocrine disruptor bisphenol A.

In this study, controlled growth of Ni-MOF was decorated in amino acid-functionalized graphene nanoplatelets (FxGnP) by a solvothermal approach. The synthesized nanocomposite was characterized by various spectral, microscopic, and electrochemical techniques. FE-SEM and TEM image results exhibited the sheet-like structure of FxGnP and spherical-like Ni-MOF with an average size of 5.6 µm. Appreciably, the size of Ni-MOF was reduced to ∼2.3 µm while introducing the FxGnP. The presence of a large number of hydroxyl and epoxy functional groups of FxGnP acts as a nucleation center and restricted the uncontrolled growth of Ni-MOF. The FxGnP-Ni-MOF composite was modified on GCE and then utilized for the oxidation of bisphenol A (BPA). The nanocomposite material showed a sharp peak at +0.38 V vs. Ag/AgCl (saturated NaCl) with a stable response for BPA due to their less particle size with high electroactive surface area and higher electrical conductance, whereas bare GCE failed to the stable determination of BPA. The developed assay for determination of BPA exhibited a wide linear range from 2 × 10-9 M to 10 × 10-6 M, LOD 0.184 × 10-9 M and sensitivity of 247.65 µA mM-1 cm-2. The FxGnP-Ni-MOF/GCE showed good stability and reproducibility against BPA. Finally, the present electrocatalyst was effectively utilized for the quantitative determination of BPA in water samples and obtained results were validated with HPLC method.

Bismuth telluride decorated on graphitic carbon nitrides based binary nanosheets: Its application in electrochemical determination of salbutamol (feed additive) in meat samples.

The design and fabrication of effective electrochemical sensor for ultrasensitive detection of feed additive and multidrug are highly significant in food analysis. In this work, we explored to develop the possibility for rapid detection of feed additive drug using bismuth telluride (Bi2Te3) decorated graphitic carbon nitrides (GCN) nanostructures as a modified electrode for electrochemical sensing. Herein, the modified electrode was focused on the development of electrocatalytic performances for the determination of salbutamol in food products. The electrochemical sensors are developed by bismuth telluride sheets interconnected with graphitic carbon nitrides sheets (Bi2Te3/GCN) on to a screen-printed carbon electrode. The binary nanosheets of Bi2Te3/GCN exhibited an enhanced electrocatalytic ability towards salbutamol detection owing to their selective adsorption, by the combination of electrostatic interaction of binary nanosheets and the formation of charge assisted interactions between salbutamol and Bi2Te3/GCN surfaces. A nanomolar limit of detection (1.36 nM) was calculated in 0.05 M phosphate buffer (PB) supporting electrolyte (pH 7.0) using differential pulse voltammetry. The linear dynamic ranges with respect to salbutamol concentration were 0.01-892.5 µM, and the sensitivity of the sensor was 36.277 µA µM-1 cm-2. The sensor stability and reproducibility performances were observed. However, the obtained results are highly satisfactory which suggest the application of binary nanosheets in real-time food analysis.

An electrochemical sensing of phenolic derivative 4-Cyanophenol in environmental water using a facile-constructed Aurivillius-structured Bi2MoO6.

Harmful chemicals are always found in the environment and it is necessary to construct a viable sensor to detect those chemicals. In order to construct an electrochemical sensing platform, designing an electrode using bismuth mixed oxides are more important and which grabbed more attention due to its high electrocatalytic ability and conductivity. In this literature, we report a facile synthesis of thorn apple like structured pure bismuth molybdate (Bi2MoO6) using a simple hydrothermal assisted one-step calcination method and we report a facile method to sense 4-cyanophenol by electrochemical technique. Bi2MoO6 modified (Glassy Carbon electrode) GCE possess two linear ranges 0.1-39.1 µM and 46.6-110.1 µM with excellent detection limit 0.008297 µM and 0.01097 µM. Also, this novel sensor is steady with good stability, repeatability, and reproducibility. Successfully, the environmental water sample is analyzed as a real sample with a feasible and quantification results which were compared with HPLC analysis.

Green sonochemical synthesis and fabrication of cubic MnFe2O4 electrocatalyst decorated carbon nitride nanohybrid for neurotransmitter detection in serum samples.

The binary nanomaterials and graphitic carbon based hybrid has been developed as an important porous nanomaterial for fabricating electrode with applications in non-enzymatic (bio) sensors. We report a fast synthesis of bimetal oxide particles of nano-sized manganese ferrite (MnFe2O4) decorated on graphitic carbon nitride (GCN) via a high-intensity ultrasonic irradiation method for C (30 kHz and 70 W/cm2). The nanocomposites were analyzed by powder X-ray diffraction, XPS, EDS, TEM to ascertain the effects of synthesis parameters on structure, and morphology. The MnFe2O4/GCN modified electrode demonstrated superior electrocatalytic activity toward the neurotransmitter (5-hydroxytryptamine) detection with a high peak intensity at +0.21 V. The appealing application of the MnFe2O4/GCN/GCE as neurotransmitter sensors is presented and a possible sensing mechanism is analyzed. The constructed electrochemical sensor for the detection of 5-hydroxytryptamine (STN) showed a wide working range (0.1-522.6 µM), high sensitivity (19.377 µA µM-1 cm-2), and nano-molar detection limit (3.1 nM). Moreover, it is worth noting that the MnFe2O4/GCN not only enhanced activity and also promoted the electron transfer rate towards STN detection. The proposed sensor was analyzed for its real-time applications to the detection of STN in rat brain serum, and human blood serum in good satisfactory results was obtained. The results showed promising reproducibility, repeatability, and high stability for neurotransmitter detection in biological samples.

Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH.

Nonalcoholic fatty liver disease (NAFLD) is currently one of most common forms of chronic liver disease globally. NAFLD represents a wide spectrum of liver involvement from nonprogressive isolated steatosis to nonalcoholic steatohepatitis (NASH), characterized by liver necroinflammation and fibrosis and currently one of the top causes of end-stage liver disease and hepatocellular carcinoma. At present, there is a lack of effective treatments, and a central barrier to the development of therapies is the requirement for an invasive liver biopsy for diagnosis of NASH. Discovery of reliable, noninvasive biomarkers are urgently needed. In this study, we tested whether circulating extracellular vesicles (EVs), cell-derived small membrane-surrounded structures with a rich cargo of bioactive molecules, may serve as reliable noninvasive "liquid biopsies" for NASH diagnosis and assessment of disease severity. Total circulating EVs and hepatocyte-derived EVs were isolated by differential centrifugation and size-exclusion chromatography from serum samples of healthy individuals, patients with precirrhotic NASH, and patients with cirrhotic NASH. EVs were further characterized by flow cytometry, electron microscopy, western blotting, and dynamic light scattering assays before performing a proteomics analysis. Our findings suggest that levels of total and hepatocyte-derived EVs correlate with NASH clinical characteristics and disease severity. Additionally, using proteomics data, we developed understandable, powerful, and unique EV-based proteomic signatures for potential diagnosis of advanced NASH. Conclusion: Our study shows that the quantity and protein constituents of circulating EVs provide strong evidence for EV protein-based liquid biopsies for NAFLD/NASH diagnosis.

Identification of a Novel Hepatitis C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 Genotypes.

Background: Hepatitis C virus (HCV) exhibits great genetic diversity and is classified into 7 genotypes (GTs), with varied geographic prevalence. Until the recent development of pangenotypic direct-acting antiviral regimens, the determination of HCV GT was necessary to inform optimal treatment. Methods: Plasma samples with unresolved GT using standard commercial genotyping methods were subjected to HCV full-genome sequencing, and phylogenetic analysis was performed to assign GT. Results: Four patients, previously classified as GT5 by LiPA or Abbott RealTime polymerase chain reaction assays, were identified as infected with a novel HCV GT. This novel HCV GT, GT8, is genetically distinct from previously identified HCV GT1-7 with >30% nucleotide sequence divergence to the established HCV subtypes. All 4 patients were originally from Punjab, India, but now reside in Canada and are epidemiologically unlinked. Despite presence of baseline resistance-associated substitutions within the GT8 virus of all 4 patients (NS3: V36L, Q80K/R; NS5A: Q30S, Y93S), all patients achieved a sustained virologic response; 2 treated with sofosbuvir/velpatasvir/voxilaprevir for 8 weeks, 1 with sofosbuvir/ledipasvir plus ribavirin for 24 weeks and 1 with sofosbuvir plus daclatasvir for 12 weeks. Conclusions: The discovery of a novel HCV GT8 confirms the circulation of this newly identified lineage in the human population.

Crystal structure of l-tryptophan-fumaric acid-water (1/1/1).

In the title compound, C11H12N2O2·C4H4O4·H2O, the l-tryp-to-phan mol-ecule crystallized as a zwitterion, together with a neutral fumaric acid mol-ecule and a water solvent mol-ecule. In the crystal, the three components are linked by a series of N-H⋯O, O-H⋯O and C-H⋯O hydrogen bonds, forming slabs lying parallel to (001). The slabs are connected by O-H⋯O hydrogen bonds, involving inversion-related fumaric acid groups, leading to the formation of a three-dimensional structure.

Forearm and hand arteries' aneurysms ­ a case report of bilateral true ulnar artery aneurysm in the hypothenar eminence and systematic review of the literature.

Arterial aneurysms in the forearm, wrist and hand are relatively uncommon. Penetrating injuries, arterial traumas, infections and repetitive microtraumas represent the most frequent cause of these secondary aneurysms or pseudo-aneurysms, while true nontraumaticor infective peripheral aneurysms of the upper extremities are very rarely encountered. Over the last 20 years these have been reported only sporadically, both in adults and children. We describe a case of bilateral true idiopathic saccular artery aneurysms in the hypothenar eminence, treated with excision and arterial continuity restoration by primary end-to-end anastomosis on the left side and conservatively on the right. To our knowledge, no other similar case has been documented to date. Starting from this original case we conducted a systematic review of the literature via PubMed search on peripheral aneurysms of the forearm and hand arteries from 1933 to the present, including specifically true distal ulnar and radial artery aneurysms. Etiology, clinical characteristics and management of these rare pathological entities are extensively discussed.

Anticoagulation therapy for postoperative deep vein thrombosis coupled with pulmonary embolism: a potential trigger for delayed popliteal artery injury presentation after total knee arthroplasty.

OBJECTIVES: A case of delayed popliteal artery injury (PA-INJ) onset after total knee arthroplasty (TKA) in a patient under postoperative anticoagulation therapy is reported. The role of anticoagulation both in late PA-INJ presentation and in PA-INJ management is discussed. REPORT: An obese 76-year-old woman was presented with a common femoral vein thrombosis coupled with pulmonary embolism five days after TKA. She was immediately placed under anticoagulation therapy. Four days later, during physiotherapy-supervised mobilization, she developed a calf haematoma and large retro-articular pseudoaneurysm. Angiography revealed a minor PA-INJ successively treated with a covered stent-graft. CONCLUSIONS: In cases of initially undetected and staunched TKA-related PA-INJs, postoperative anticoagulation therapy may act as a potential trigger for final arterial rupture during mobilization exercises, followed by acute bleeding; in these cases, endovascular management represents an excellent treatment option. Close clinical and instrumental monitoring is strongly recommended after TKA, in patients who imperatively require full-dose anticoagulation therapy.

Arterial entrapment syndrome in the cubital fossa: a rare cause of acute stress-related arterial thrombosis in a patient with brachial artery duplication.

Arterial entrapment syndrome (AES) at elbow level is very rare and to our knowledge no case of AES by lacertus fibrosus in the cubital fossa in presence of brachial artery duplication has been described to date. We describe a rare case of acute arterial thrombosis of one of two brachial arteries highlighted in the cubital fossa which developed after strenuous right elbow flexor muscle activity and hyper-extensions presumably related to AES by lacertus fibrosus at elbow level. A 43-year-old right-handed woman, experienced paleness, coldness and numbness of the right hand, after 8 consecutive hours of gardening. As she worked, her ipsilateral flexor elbow muscles remained in prolonged and inappropriate tension. Clinical examination evidenced the absence of radial artery pulse in the wrist and mild hypothermia in the second and third finger. During surgical exploration two anastomosed brachial arteries were detected in the cubital fossa under the lacertus fibrosus. The lateral superficial brachial artery was occluded. Intraoperative arteriography evidenced brachial artery duplication at the third superior of the arm and normal vascular pattern at the forearm level. In cases of unexplained atypical intermittent upper extremity claudication or acute ischemic symptoms an AES should always be ruled out, particularly when symptoms are exacerbated by strenuous upper extremity activity or when upper limb muscular hypertrophy is evident. In these cases a thorough dynamic clinical and instrumental examination is mandatory to confirm a diagnosis of AES and to avoid possible future ischemic complications.

Localized superficial femoral vein thrombosis coupled with iatrogenic arteriovenous fistulas presenting as pulmonary emboli.

INTRODUCTION: 'Localized' femoral vein thrombosis (FVT) is a relatively rare condition usually associated with traumas, external compression or iatrogenic etiologies and the consequence can be pulmonary embolism. REPORT: This is the case of a 46-year-old woman who presented with pulmonary emboli secondary to 'localized' superficial FVT, coupled with post-puncture arteriovenous fistulas (AVFs), two days after trans-femoral vein radio-frequency cardiac ablation. After placing a temporary IVC-filter, the AVFs were sutured directly while the residual FVT was treated conservatively. DISCUSSION: Close local monitoring and adequate medical and surgical management are mandatory to avoid possible dangerous complications, also in apparently 'low-risk' iatrogenic AVFs.

Outcome analysis of trapezectomy with and without pyrocarbon interposition to treat primary arthrosis of the trapeziometacarpal joint.

We performed a prospective cohort comparative analysis of simple trapezectomy and trapezectomy with pyrocarbon interposition in 38 consecutive patients with trapeziometacarpal joint osteoarthrosis. Patients were assessed preoperatively, at six and 12 months postoperatively using subjective and objective tools. Subjective assessment was performed using the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire and the visual analogue score. Objective assessment was performed with grip strength measurements. At each time interval, statistical differences were sought between the two subgroups. No significant difference between the two subgroups was noted at any time interval on subjective or objective assessment. A significant difference (p < 0.05) was found on comparing the respective preoperative and 12-month subjective scores in both subgroups. Of the pyrocarbon subgroup seven had related complications. We suggest that pyrocarbon interposition does not significantly improve postoperative function, requires a longer operation with a high postoperative risk of pyrocarbon displacement and need for revision surgery.

A report on various digenetic metacercariae from the freshwater fishes of River Godavari, Rajahmundry.

Fishes serve as intermediate hosts to a number of avian digenetic trematodes. A survey on 10 different species of freshwater fishes belonging to 8 families from River Godavari from August 2005 to September 2007 revealed a total of 10 metacercariae of digenetic trematodes from five families i.e., Clinostomidae Lühe, 1901; Diplostomidae Poirier, 1886; Isoparorchiidae (Travassos, 1922); Strigeidae Railliet, 1919 and Heterophyidae (Leiper, 1909) Odhner, 1914. The metacercarial fauna dominated the adult parasitic fauna of the freshwater fishes.

Long-term stability of self-assembled monolayers on 316L stainless steel.

316L stainless steel (316L SS) has been extensively used for making orthopedic, dental and cardiovascular implants. The use of phosphonic acid self-assembled monolayers (SAMs) on 316L SS has been previously explored for potential biomedical applications. In this study, we have investigated the long-term stability of methyl (-CH(3)) and carboxylic acid (-COOH)-terminated phosphonic acid SAMs on 316L under physiological conditions. The stability of SAMs on mechanically polished and electropolished 316L SS was also investigated as a part of this study. Well-ordered and uniform -CH(3)- and -COOH-terminated SAMs were coated on mechanically polished and electropolished 316L SS surfaces. The long-term stability of SAMs on 316L SS was investigated for up to 28 days in Tris-buffered saline (TBS) at 37 degrees C using x-ray photoelectron spectroscopy, atomic force microscopy and contact angle goniometry. A significant amount of phosphonic acid molecules was desorbed from the 316L SS surfaces within 1 to 7 days of TBS immersion followed by a slow desorption of molecules over the remaining days. The -COOH-terminated SAM was found to be more stable than the -CH(3)-terminated SAM on both mechanically and electropolished surfaces. No significant differences in the desorption behavior of SAMs were observed between mechanically and electropolished 316L SS surfaces.

The role of mini-fragment screw fixation in volar dislocations of the proximal interphalangeal joint.

Palmar fracture-dislocations of the proximal interphalangeal (PIP) joint are uncommon injuries, which can be associated with long-term complications if sub-optimally treated. We report two cases of palmar fracture-dislocations of the PIP joint treated by open reduction and internal fixation using a single mini-fragment screw. The long term results of hand and finger function were excellent.

Merits of performing coronary artery by-pass grafts on the beating heart.

A retrospective study of 1006 patients was undertaken to evaluate the benefit of a change of strategy in performing coronary artery by-pass grafting surgery. Group A consisted of 500 patients who were consecutively operated on cardiopulmonary by-pass and group B consisted of 506 patients who were consecutively operated on using "off pump" techniques. Pre-operative risk profile in both groups were similar as was as in the operating time. There was distinct benefit in amount of homologous transfusion, period of ICU stay, increased usage of radial artery conduit and improvement in transoesophageal echocardiography assessment of ischaemic mitral incompetence immediately after revascularisation in off pump (group B). Though there was a lower mortality in group B ie, 3/506 vis-a-vis 10/500 in group A this is not of statistical significance. Improvement in left ventricular ejection fraction >5.0% occurred more frequently in one month follow-up visits of group B patients. Period of return to active life was also shorter (28 versus 56 days). Based on observations, we conclude that there is a distinct benefit in avoiding cardiopulmonary by-pass while performing coronary artery by-pass grafting.

Palmar dislocation of the proximal interphalangeal joint--an injury not to be missed.

Palmar dislocations of the proximal interphalangeal (PIP) joint are associated with long term complications if suboptimally treated. Six cases of palmar dislocation of the PIP joint are presented and a systematic approach in the diagnosis and management of such injuries in the accident and emergency department is described.