Current trends in image-guided chest interventions.

Interventional radiology (IR) is a rapidly expanding medical subspecialty and refers to a range of image-guided procedural techniques. The image guidance allows real-time visualization and precision placement of a needle, catheter, wire and device to deep body structures through small incisions. Advantages include reduced risks, faster recovery and shorter hospital stays, lower costs and less patient discomfort. The range of chest interventional procedures keeps on expanding due to improved imaging facilities, better percutaneous assess devices and advancing ablation and embolization techniques. These advances permit procedures to be undertaken safely, simultaneously and effectively, hence escalating the role of IR in the treatment of chest disorders. This review article aims to cover the latest developments in some image-guided techniques of the chest, including thermal ablation therapy of lung malignancy, targeted therapy of pulmonary embolism, angioplasty and stenting of mediastinal venous/superior vena cava occlusion, pulmonary arteriovenous malformation treatment and bronchial artery embolization for haemoptysis.

Operationalising the "One Health" approach in India: facilitators of and barriers to effective cross-sector convergence for zoonoses prevention and control.

BACKGROUND: There is a strong policy impetus for the One Health cross-sectoral approach to address the complex challenge of zoonotic diseases, particularly in low/lower middle income countries (LMICs). Yet the implementation of this approach in LMIC contexts such as India has proven challenging, due partly to the relatively limited practical guidance and understanding on how to foster and sustain cross-sector collaborations. This study addresses this gap by exploring the facilitators of and barriers to successful convergence between the human, animal and environmental health sectors in India. METHODS: A mixed methods study was conducted using a detailed content review of national policy documents and in-depth semi-structured interview data on zoonotic disease management in India. In total, 29 policy documents were reviewed and 15 key informant interviews were undertaken with national and state level policymakers, disease managers and experts operating within the human-animal-environment interface of zoonotic disease control. RESULTS: Our findings suggest that there is limited policy visibility of zoonotic diseases, although global zoonoses, especially those identified to be of pandemic potential by international organisations (e.g. CDC, WHO and OIE) rather than local, high burden endemic diseases, have high recognition in the existing policy agenda setting. Despite the widespread acknowledgement of the importance of cross-sectoral collaboration, a myriad of factors operated to either constrain or facilitate the success of cross-sectoral convergence at different stages (i.e. information-sharing, undertaking common activities and merging resources and infrastructure) of cross-sectoral action. Importantly, participants identified the lack of supportive policies, conflicting departmental priorities and limited institutional capacities as major barriers that hamper effective cross-sectoral collaboration on zoonotic disease control. Building on existing informal inter-personal relationships and collaboration platforms were suggested by participants as the way forward. CONCLUSION: Our findings point to the importance of strengthening existing national policy frameworks as a first step for leveraging cross-sectoral capacity for improved disease surveillance and interventions. This requires the contextual adaptation of the One Health approach in a manner that is sensitive to the underlying socio-political, institutional and cultural context that determines and shapes outcomes of cross-sector collaborative arrangements.

Dentistry and the Pandemic: A Year of Reckoning.

In March 2020, the world that we know irrevocably changed forever. It feels like "Groundhog Day" all over again, and it seems that the nightmare is here to stay. It all began on the January 8, 2020, when China grimly announced that coronavirus disease-2019 (COVID-19) pandemic is caused by the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2)1 but it was not until March 2020 that the situation swiftly careened out of control and is unequivocally posing the greatest challenge to humanity worldwide since the end of the Second World War. While the scientific community heroically galvanized itself and raced against time to provide viable solutions to this formidable foe in the form of vaccines, the worldwide dental fraternity has had to grapple with an extraordinary situation evolving in real-time and ensure that we responded robustly to this daunting health emergency that has spared no corner of our beloved planet. Initially, COVID-19 ensured cessation of all non-urgent dental care in most parts of the world but with increasingly significant inputs about the nature of the pathogen from the scientific community, the dental community has been able to cobble together a workable plan in reconfiguring and restructuring the dental practice in consonance with the situation at hand. It is fiendishly arduous to estimate the massive impact on the dental profession, but it is safe to assume it to be substantial.

Autophagy: The "Pac-Man" within Us-Ally or Adversary?

Autophagy, first described by the Belgian biochemist Christian De Duve in 1963, is derived from the Greek word "autóphagos," which means "self-devouring." It is a cellular homeostatic process in which the body rids itself of flawed or damaged cells and other defective cellular organelles.1 The implication of defective autophagy in various human diseases has been well documented. The vital importance of autophagy is underscored by the fact that robust cellular health and function are intricately linked with it.

Investigation of propagation dynamics of truncated vector vortex beams.

In this Letter, we experimentally investigate the propagation dynamics of truncated vector vortex beams generated using a Sagnac interferometer. Upon focusing, the truncated vector vortex beam is found to regain its original intensity structure within the Rayleigh range. In order to explain such behavior, the propagation dynamics of a truncated vector vortex beam is simulated by decomposing it into the sum of integral charge beams with associated complex weights. We also show that the polarization of the truncated composite vector vortex beam is preserved all along the propagation axis. The experimental observations are consistent with theoretical predictions based on previous literature and are in good agreement with our simulation results. The results hold importance as vector vortex modes are eigenmodes of the optical fiber.

Novel highly selective inhibitors of ubiquitin specific protease 30 (USP30) accelerate mitophagy.

Mitophagy is one of the processes that cells use to maintain overall health. An E3 ligase, parkin, ubiquitinates mitochondrial proteins prior to their degradation by autophagasomes. USP30 is an enzyme that de-ubiquitinates mitochondrial proteins; therefore, inhibiting this enzyme could foster mitophagy. Herein, we disclose the structure-activity relationships (SAR) within a novel series of highly selective USP30 inhibitors. Two structurally similar compounds, MF-094 (a potent and selective USP30 inhibitor) and MF-095 (a significantly less potent USP30 inhibitor), serve as useful controls for biological evaluation. We show that MF-094 increases protein ubiquitination and accelerates mitophagy.

Oryzanol as natural antioxidant for improving sunflower oil stability.

Sunflower oil is being made shelf stable by the incorporation of synthetic antioxidants such as tertiary butyl hydroquinone (TBHQ), while natural antioxidants like oryzanol and tocopherols can also be used. The aim of the current investigation was to evaluate the antioxidant effect of natural oryzanol (Oz) concentrate (15.5 % oryzanol) and purified Oz (80 % oryzanol) on oxidative and thermal stability of sunflower oil. Sunflower oil was incorporated with Oz concentrate to provide 0, 0.12, 0.25, 0.50, 0.84, 1.0, 1.60, 2.0, 2.5 and 3.20 % oryzanol in the oil, stored for 5 weeks at 37 °C and oxidative stability was evaluated. It was found that the oryzanol concentrate showed good antioxidant effect with increase in concentration of oryzanol. In another set of experiments, sunflower oil containing purified Oz at 1 % level individually and in combination with 0.1 % α- tocopherol (α-T) was heated at 120 °C for 24 h to evaluate thermal stability. Sunflower oil containing 1 % Oz (80 % purity) showed 98.40 % and sunflower oil containing 1 % Oz and 0.1 % α-T showed 108.75 % antioxidant effect compared to TBHQ taken as 100 %. The study indicated that sunflower oil containing 1 % Oz (80 % purity) and 0.1 % α-T combination provides a synergistic effect in inhibiting primary and secondary products and showed highest thermal stability. SFO containing 1 % Oz added as concentrate also showed good antioxidant effect during storage. Hence, instead of using synthetic antioxidants like TBHQ, we can add natural oryzanol (purified or as concentrate) to sunflower oil to increase its oxidative and thermal stability.

Amberlite IR-120H catalyzed MCR: design, synthesis and crystal structure analysis of 1,8-dioxodecahydroacridines as potential inhibitors of sirtuins.

A rapid, inexpensive and high yielding method has been developed for the synthesis of 1,8-dioxodecahydroacridines using Amberlite IR-120H as a reusable catalyst under open air. These compounds were designed as potential inhibitors of sirtuins and prepared via the MCR of 5,5-dimethyl-1,3-cyclohexanedione, (hetero)aryl aldehydes and (hetero)aromatic amines under mild conditions. Further structure elaboration of a representative compound was performed via Pd catalyzed C-C bond forming reactions. The crystal structure analysis and H-bonding patterns along with in vitro inhibitory activity against yeast Sir2 of the same compound is presented. Docking studies indicated that the compound interacts well with the yeast Sir2.

Synthesis and evaluation of antioxidant properties of novel 1,2,4-triazole-based schiff base heterocycles.

A series of 1,2,4-triazole-based Schiff base heterocyclic compounds (5a-f and 8a-i) and phenethylamines (7a-h) were synthesized and evaluated for antioxidant properties by free-radical scavenging, anti-hemolytic activity, lipid peroxidation, and their protective effects against DNA oxidative damage. Compounds 7c, 7d, 7h, 8b, and 8i showed promising DPPH(•) radical scavenging activity with the level of inhibition between 86.8% and 94%. Compounds 8a, 8b, 8d, 8g, and 8i were effective against the oxidative hemolysis of human erythrocytes and lipid peroxidation, in a dose-dependent manner, with IC50 values in the range of 55.7-80.7 and 53.2-81.2 µg/mL, respectively. Compounds 8a and 8b were effective against oxidative damage on erythrocyte ghost membrane proteins, and 8g and 8i were able to protect against DNA oxidative damage.

An article on "letter to the editor".

A 'Letter to the Editor' is an abbreviated form of communication where 'readers' can express their carefully considered scientific opinion about a recently published article in a journal. It is considered as 'post-publication peer review'. There are certain things that a letter writer and the 'editor' need to keep in mind while writing a 'Letter' for a journal. The 'editor' needs to curate the contents of the 'Letter' and make sure that there are no misinformation shared. The formatting, type, scope and the scientific quality of the 'Letter' depend on the journal that publishes them, and hence, different publications may require their 'letter writers' to present the information that they want in a certain way. The following article reflects an overview of the role of editors and writers, guidelines, scope, and format of the 'Letter to the Editor'.

Bioefficacy, dissipation kinetics and safety evaluation of selected insecticides in Allium cepa L.

This paper reports the bioefficacy of selected insecticides against thrips and their pre-harvest intervals (PHI) in onion pertaining to their recommended application rates and maximum residue limits. Profenophos, methomyl and imidacloprid showed comparatively higher bioefficacy against thrips. GC-MS and LC-MS/MS-based residue analysis methods in onion bulbs and composite matrix of bulbs+leaves were thoroughly validated. The residue data for bulb+leaves was assessed with reference to the EU-MRLs applicable for spring onion. Dimethoate was the most stable chemical with PHI of 52.5 days, followed by monocrotophos (24 days) and carbofuran (20.5 days). The PHIs of profenophos, chlorpyrifos, methomyl and cypermethrin were similar and within the range of 10-13 days. Imidacloprid and λ-cyhalothrin had similar PHI of 4.5 days. Spinosad was the fastest-degrading chemical with PHI of 2 days. The combined bioefficacy and residue dynamics information will support label-claim of these insecticides for the management of thrips in onion, help in scheduling their applications in pest management program as per relative PHIs and minimize the residue accumulations at harvest. The dietary exposure was less than the maximum permissible intake for most of the insecticides on all sampling days except for dimethoate and monocrotophos.

Temperature-dependent coaggregation of eye lens αB- and ß-crystallins.

Crystallin is essential not only for the maintenance of eye lens transparency, but also in the biology of other tissues. Eye lens α-crystallin exists as a heteropolymer composed of two homologous subunits, αA and αB. Despite the critical role of α-crystallin in many tissues, little is known regarding structural and functional significance of the two subunits. Herein, we describe a unique feature of αB-crystallin. At high temperatures (>70°C) not only αB-crystallin aggregates but also enhances the aggregation of other lens proteins. Intriguingly, αB-crystallin-mediated coaggregation at and above 70°C involves ß- but not γ-crystallin. Further, αA-crystallin, but not a mutant (F71L) αA-crystallin, prevented aggregation of αB-crystallin and also reduced coaggregation of αB- and ß-crystallin. These studies explain the rationale for the existence of α-crystallin heteropolymer with αA subunit as a major partner that is vital for lens transparency and provide insights into αB-crystallin-induced coaggregation which may have a bearing in some pathological conditions where αB-crystallin is overexpressed.

Novel pyrazole-3-carboxamide derivatives as cannabinoid-1 (CB1) antagonists: journey from non-polar to polar amides.

The synthesis and biological evaluation of novel pyrazole-3-carboxamide derivatives as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced. In general, a range of modifications were well tolerated. Several molecules with high polar surface area were also identified as potent CB1 receptor antagonists. The in vivo proof of principle for weight loss is exemplified with a lead compound from this series.

Structure-activity relationship studies of novel pyrazole and imidazole carboxamides as cannabinoid-1 (CB1) antagonists.

The synthesis and biological evaluation of novel pyrazole and imidazole carboxamides as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced on rimonabant template. The central pyrazole core was also replaced with its conformationally constrained motif and imidazole moieties. In general, a range of modifications were well tolerated. Several molecules with low- and sub-nanomolar potencies were identified as potent CB1 receptor antagonists. The in vivo proof of principle for weight loss is demonstrated with a lead compound in DIO mice model.

Synthesis, characterization, DNA binding properties, fluorescence studies and toxic activity of cobalt(III) and ruthenium(II) polypyridyl complexes.

The new ligand 4-(isopropylbenzaldehyde)imidazo[4,5-f ][1,10]phenanthroline (ippip) and its complexes [Ru(phen)(2)(ippip)](2+)(1),[Co(phen)(2)(ippip)](3+)(2),[Ru(bpy)(2)(ippip)](2+)(3),[Co(bpy)(2)(ippip)](3+)(4)(bpy=2,2-bipyridine) and (phen=1,10-phenanthroline) were synthesized and characterized by ES(+)-MS, (1)H and (13)C NMR. The DNA binding properties of the four complexes were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that complexes bind to calf thymus DNA (CT-DNA) through intercalation. When irradiated at 365 nm, the complexes promote the photocleavage of pBR322 DNA, and complex 1 cleaves DNA more effectively than 2, 3, 4 complexes under comparable experimental conditions. Furthermore, photocleavage studies reveal that singlet oxygen ((1)O(2)) plays a significant role in the photocleavage.

Simultaneous combined liver and kidney transplantation: a single center experience.

Renal dysfunction is common in patients awaiting liver transplantation (LT) and affects outcome following LT. Combined liver and kidney transplantation (CLKT) has been proposed as effective treatment for patients with chronic diseases of both organs, some with hepatorenal syndrome and for liver-based metabolic diseases affecting kidney. This study is undertaken to analyze results of CLKT at a single center. Of 2690 LTs performed between 1992 and 2007, there were 39 CLKTs; most common indications were metabolic, cirrhosis and polycystic disease. With follow-up of up to 170 months, 11 died (overall survival 71.8%); one-, five-, and 10-yr patient and liver graft survival is 77%, 73.7%, and 73.7%, respectively, and kidney graft survival is 77%, 70%, and 70%, respectively. Survival among metabolic group (78.6%) appeared to be better than non-metabolic group (68%); however, this difference was not significant (p = 0.39). Fifteen surviving patients (53.6%) have mild/moderate renal impairment (creatinine > or = 125 micromol/L). None has severe renal failure (serum creatinine > or = 250 micromol/L) or end-stage renal disease requiring hemodialysis. CLKT has good results in selected groups of patients. It provides protection to kidney allograft in liver-based metabolic diseases affecting kidney. The rate of acute rejection episodes of kidney is low. Significant proportion develops long-term mild/moderate renal dysfunction. Careful attention to immunosuppression to minimize nephrotoxicity may help.

Differential outcomes from metabolic ratios in the identification of CYP2D6 phenotypes--focus on venlafaxine and O-desmethylvenlafaxine.

BACKGROUND: Venlafaxine (VEN), a well accepted anti-depressant, is metabolized through the cytochrome P 450 (CYP) 2D6 isozyme to form O-desmethyvenlafaxine (ODV). Due to the involvement of CYP2D6, the formation of ODV is influenced by genetic polymorphism. We used standard tools of assessment to explore the phenotypic distribution in a retrospective manner using the pharmacokinetic (PK) data of VEN and ODV obtained from several bioavailability/bioequivalence (BA/BE) studies in healthy subjects using the reference formulation. METHODS: Four single oral dose, open-label, randomized crossover BA/BE studies of VEN (doses: 37.5-150 mg) were performed in 141 healthy subjects. Plasma samples were collected over a period 72 h post VEN administration. The samples were analyzed for VEN and ODV using a validated LC/MS/MS assay with a limit of quantification 2.073 ng/mL for VEN and 3.973 ng/mL for ODV. PK parameters (C(max), T(max), AUC (0-t), AUC(0-infinity), t(1/2)) were computed using the noncompartmental approach. AUC metabolic ratios of VEN/ODV and ODV/VEN were computed for all subjects and were subjected to normality test procedures to tease out phenotypic distribution. RESULTS: ODV/VEN and VEN/ODV AUC metabolic ratios were evaluated for standard normal distribution and outliers to determine phenotypic distribution. Use of the VEN/ODV AUC metabolic ratio, arranged in a rank order, resulted in a distribution that distinguished poor metabolizers (PM) and extensive metabolizers (EM). The application of the ODV/VEN AUC metabolic ratio showed a unique distribution that distinguished ultra metabolizers (UM) and extensive metabolizers. By using both metabolic ratios, 141 healthy subjects were classified as follows: PMs = 18, EMs = 118, UMs = 5. Regardless of the formulation or dose size used, the plasma concentration-time profiles for both VEN and ODV were distinct amongst the three phenotypes identified in this work. CONCLUSIONS: The use of VEN/ODV and ODV/VEN AUC metabolic ratios suggested quantitative differences. The data support the use of ODV/VEN but not VEN/ODV metabolic ratio for the identification of UM phenotypes of VEN. The derived metabolic ratios of ODV/VEN from this work were in line with other studies that used both phenotypic and genotypic correlation strategies for VEN.

Safety and toxicological evaluation of a novel anti-obesity formulation LI85008F in animals.

LI85008F is a novel synergistic composition of Moringa oleifera, Murraya koenigi, and Curcuma longa. These herbs are well recognized and widely used in ayurvedic system of medicine for treating a variety of diseases and are also have been used for culinary purposes for thousands of years. LI85008F inhibits preadipocyte differentiation and potentiates lipid breakdown in mature adipocytes. In diet-induced obese rats, LI85008F significantly reduced weight gain and improved serum adiponectin levels. These findings motivated the authors to determine the broad-spectrum safety of LI85008F. Acute oral toxicity, acute dermal toxicity, primary skin irritation, primary eye irritation, and dose-dependent 28-day sub-acute toxicity studies were conducted. The acute oral LD50 of LI85008F was greater than 5000 mg/kg in female SD rats and no changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of LI85008F was greater than 2000 mg/kg. LI85008F was classified as non-irritating to skin in a primary dermal irritation study conducted using New Zealand Albino rabbits. LI85008F caused minimal irritation to eyes in a primary eye irritation test conducted on New Zealand Albino rabbits. A dose-dependent 28-day sub-acute toxicity study demonstrated no significant changes in selected organ weights. Evaluations on hematology, clinical chemistry, and histopathology did not show any significant adverse changes. The NOAEL of LI85008F was found to be greater than 2500 mg/kg body weight. These results demonstrate the broad spectrum safety of LI85008F in animal models.

Effectiveness and safety of autologous platelet-rich plasma therapy with total contact casting versus total contact casting alone in treatment of trophic ulcer in leprosy: An observer-blind, randomized controlled trial.

BACKGROUND: Trophic ulcers secondary to leprosy pose a great stigma to patients and remain a challenge to the treating dermatologists. Platelet-rich plasma (PRP) introduces growth factors directly into the wound and aids in rapid healing. The role of PRP in the treatment of trophic ulcers in leprosy patients has not yet been established by randomized controlled trials. AIMS: To study the effectiveness and safety of autologous PRP therapy with total contact casting versus total contact casting alone in the treatment of trophic ulcers in leprosy. METHODS: In an observer-blind, randomized (1:1) controlled study, 118 patients were enrolled. PRP was prepared by the manual double-spin method (1600 rpm for 10 min followed by 4000 rpm for 10 min). After wound bed preparation, activated PRP was injected intra- and perilesionally, and platelet-poor plasma gel was applied over the ulcer bed. Occlusive dressings and total contact casting were then applied in Group A, and only total contact casting was applied in Group B. The same procedure was repeated every 2 weeks for 8 weeks. RESULTS: In all, 56 patients were analyzable in Group A and 52 in Group B. The surface area of the ulcer decreased significantly from first follow-up onward in both the groups (P < 0.001 in both the groups). Intergroup comparison showed that the reduction in the surface area of the ulcer was significantly more in Group A than in Group B from the first follow-up onward (P = 0.038) and the difference was maintained till the fifth follow-up (P < 0.001). At the end of the study, 91.10 ± 9.65% ulcer surface area reduction had occurred in Group A, whereas it was 79.77 ± 17.91% in Group B (P < 0.001). Trophic ulcers healed completely more often in paucibacillary leprosy patients (P < 0.001) and in those with a lower initial surface area of the ulcer (P < 0.001). LIMITATION: Short duration of treatment (8 weeks). CONCLUSION: PRP combined with total contact casting accelerates the healing of trophic ulcers of leprosy and is more effective than total contact casting alone. Complete remission is more likely to occur when the duration and surface area of ulcer are less and in the paucibacillary spectrum.

Structural and kinetic properties of Bacillus subtilis S-adenosylmethionine synthetase expressed in Escherichia coli.

S-adenosylmethionine (SAM) synthetase (EC 2.5.1.6) catalyzes the synthesis of S-adenosylmethionine using l-methionine and ATP as substrates. SAM synthetase gene (metE) from Bacillus subtilis was cloned and over-expressed, for the first time, in the heterologus host Escherichia coli as an active enzyme. Size-exclusion chromatography (SEC) revealed a molecular weight of ~180 kDa, suggesting that the enzyme is a homotetramer stabilized by non-covalent interactions. SAM synthetase exhibited optimal activity at pH 8.0 and 45 degrees C with the requirement of divalent cation Mg(2+), and stimulated by the monovalent cation K(+). The enzyme followed sequential mechanism with a V(max) of 0.362 micromol/min/mg, and a K(m) of 920 microM and 260 microM for ATP and l-methionine, respectively. The urea-induced unfolding equilibrium of the recombinant enzyme revealed a multistate process, comprising partially unfolded tetramer, structural dimer, structural monomer and completely unfolded monomer, as evidenced by intrinsic and extrinsic fluorescence, circular dichroism (CD) and SEC. Absence of trimer in the SEC implicates that the enzyme is a dimer of dimer. Concordance between results of SEC and enzyme activity in the presence of urea amply establishes that tetramer alone with intersubunit active site(s) exhibits enzyme activity.