Behavior of Microstrain in Nd3+-Sensitized Near-Infrared Upconverting Core-Shell Nanocrystals for Defect-Induced Tailoring of Luminescence Intensity.

In an attempt to optimize the upconversion luminescence (UCL) output of a Nd3+-sensitized near-infrared (808 nm) upconverting core-shell (CS) nanocrystal through deliberate incorporation of lattice defects, a comprehensive analysis of microstrain both at the CS interface and within the core layer was performed using integral breadth calculation of high-energy synchrotron X-ray (λ = 0.568551 Å) diffraction. An atomic level interpretation of such microstrain was performed using pair distribution function analysis of the high-energy total scattering. The core NC developed compressive microstrain, which gradually transformed into tensile microstrain with the growth of the epitaxial shell. Such a reversal was rationalized in terms of a consistent negative lattice mismatch. Upon introduction of lattice defects into the CS systems upon incorporation of Li+, the corresponding UCL intensity was maximized at some specific Li+ incorporation, where the tensile microstrain of CS, compressive microstrain of the core, and atomic level disorders exhibited their respective extreme values irrespective of the activator ions.

Severity and Outcome of Post-Vaccine COVID-19 among Healthcare Workers in a University Hospital in India.

Healthcare workers (HCWs) are at high risk of COVID-19 infection despite vaccination. Limited data exist on COVID-19 cases among vaccinated HCWs. This study aimed to describe the clinical characteristics and outcomes of RT PCR-confirmed COVID-19 cases in vaccinated HCWs, at a COVID clinic in a medical college hospital. This single-center, prospective cohort study included HCWs who received at least one dose of the COVID-19 vaccine and tested positive for COVID-19 within 6 months. Data on demographics, symptoms, work category, COVID-19 vaccination interval, and infection severity were collected. Of 2381 vaccinated HCWs, 105 tested positive and were categorized as mild, moderate, or severe cases. Among vaccinated HCWs, 4.41% had post-vaccine COVID-19 infections. All 105 cases received the first dose, and 79 received the second dose. Of the cases, 47.6% were partially vaccinated, and 53.3% were breakthrough cases. The mean age was 30.90±8.69 years, with 63.8% male and 36.2% female cases. Most cases (85.7%) acquired infection in the hospital, and 47.6% had direct contact with COVID-19 patients. Common symptoms included fatigue (85.7%), fever (82.9%), and cough (64.8%). Among cases, 93.3% were mild, 5.7% were moderate, and 0.9% were severe. Hospital admission and supplemental oxygen therapy were required for moderate and severe cases. No mortality was reported. Certain variables were associated with age, preventive measures, workplace type, symptoms, and comorbidities. Breakthrough infections can occur among fully vaccinated HCWs but with reduced severity and mortality. Monitoring and infection control measures remain crucial even in vaccinated individuals. This study provides insights into clinical presentations, oxygen therapy requirements, and outcomes of post-vaccine COVID-19 cases among HCWs. The data will inform strategies for booster doses to prevent COVID-19.

One-Step High-Temperature Electrodeposition of Fe-Based Films as Efficient Water Oxidation Catalysts.

Electrolysis of water to produce hydrogen requires an efficient catalyst preferably made of cheap and abundant metal ions for the improved water oxidation reaction. An Fe-based film has been deposited in a single step by electrochemical deposition at temperatures higher than the room temperature. Until now, the electrodeposition of iron oxide has been carried out at 298 K or at lower temperatures under a controlled atmosphere to prohibit atmospheric oxidation of Fe2+ of the iron precursor. A metal inorganic complex, ferrocene, and non-aqueous electrolyte medium propylene carbonate have been used to achieve electrodeposition of iron oxide without the need of any inert or controlled atmosphere. At 298 K, the amorphous film was formed, whereas at 313 K and at higher temperatures, the hematite film was grown, as confirmed by X-ray diffraction. The transformation of iron of the ferrocene into a higher oxidation state under the experimental conditions used was further confirmed by X-ray photoelectron spectroscopy, ultraviolet-visible, and electron paramagnetic resonance spectroscopic methods. The films deposited at 313 K showed the best performance for water oxidation with remarkable long-term electrocatalytic stability and an impressive turnover frequency of 0.028 s-1 which was 4.5 times higher than that of films deposited at 298 K (0.006 s-1). The observed overpotential to achieve a current density of 10 mA cm-2 was found to be 100 mV less for the film deposited at 313 K compared to room-temperature-derived films under similar experimental conditions. Furthermore, electrochemical impedance data revealed that films obtained at 313 K have the least charge transfer resistance (114 Ω) among all, supporting the most efficient electron transport in the film. To the best of our knowledge, this is the first-ever report where the crystalline iron-based film has been shown to be electrodeposited without any post-deposition additional treatment for alkaline oxygen evolution reaction application.

1-[4-(2-Dimethylaminoethoxy)phenylcarbonyl]-3,5-Bis(3,4,5-Trimethoxybenzylidene)- 4-Piperidone Hydrochloride and Related Compounds: Potent Cytotoxins Demonstrate Greater Toxicity to Neoplasms than Non- Malignant Cells.

BACKGROUND: The incidence of cancer has been increasing worldwide. Unfortunately, the drugs used in cancer chemotherapy are toxic to both neoplasms and normal tissues, while many available medications have low potencies. Conjugated α,ß-unsaturated ketones differ structurally from contemporary anticancer medications , some of which have noteworthy antineoplastic properties. OBJECTIVES: This study aimed to design and synthesize highly potent cytotoxins with far greater toxicity to neoplasms than to non-malignant cells. METHODS: A series of N-acyl-3,5-bis(benzylidene)-4-piperidone hydrochlorides 4a-n were prepared and evaluated against Ca9-22, HSC-2, HSC-3, and HSC-4 squamous cell carcinomas as well as against HGF, HPLF, and HPC non-malignant cells. QSAR and western blot analyses were performed. RESULTS: The majority of compounds display submicromolar CC50 values towards the neoplasms; the figures for some of the compounds are below 10-7 M. In general, 4a-n have much lower CC50 values than those of melphalan, 5-fluorouracil, and methotrexate, while some compounds are equitoxic with doxorubicin. The compounds are far less toxic to the non-malignant cells, giving rise to substantial selectivity index (SI) figures. A QSAR study revealed that both potency and the SI data were controlled to a large extent by the electronic properties of the substituents in the arylidene aryl rings. Two representative compounds, 4f and 4g, caused apoptosis in HSC-2 cells. CONCLUSION: The compounds in series 4 are potent cytotoxins displaying tumor-selective toxicity. In particular, 4g with an average CC50 value of 0.04 µM towards four malignant cell lines and a selectivity index of 46.3 is clearly a lead molecule that should be further evaluated.

Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring.

A series of 3,5-bis(benzylidene)-4-piperidones 2a-u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF) and human pulp cells (HPC), thereby demonstrating tumour-selective toxicity. A further study revealed that most of the compounds in series 2 were more toxic to the human Colo-205 adenocarcinoma cell line (Colo-205), human HT29 colorectal adenocarcinoma cells (HT-29) and human CEM lymphoid cells (CEM) neoplasms than towards non-malignant human foreskin Hs27 fibroblast line (Hs27) cells. The potency of the cytotoxins towards the six malignant cell lines increased as the sigma and sigma star values of the aryl substituents rose. Attempts to condense various aryl aldehydes with 2,2,6,6-tetramethyl-4-piperidone led to the isolation of some 1,5-diaryl-1,4-pentadien-3-ones. The highest specificity for oral cancer cells was displayed by 2e and 2r. In the case of 2r, its selective toxicity exceeded that of doxorubicin and melphalan. The enones 2k, m, o have the highest SI values towards colon cancer and leukemic cells. Both 2e,r inhibited mitosis and increased the subG1 population (with a transient increase in G2/M phase cells). Slight activation of caspase-3, based on the cleavage of poly(ADP-ribose)polymerase (PARP) and procaspase 3, was detected.

Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts.

A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a-h and related quaternary ammonium salts 4a-h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series 3 and 4 to be potent cytotoxins with submicromolar CC50 values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure-activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, 3a-h are cytotoxic towards a number of leukemic and colon cancer cells. 4b,c lowered the mitochondrial membrane potential in CEM cells, and 4d induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely 3c,d and 4c-e, were identified as lead molecules that have drug-like properties.

Design, Syntheses, and Bioevaluations of Some Novel N2-Acryloylbenzohydrazides as Chemostimulants and Cytotoxic Agents.

A series of novel N2-acryloylhydrazides 1a-m and a related series of compounds 6a-c were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound N1-(3,4-dimethoxyphenylcarbonyl)-N2-acryloylhydrazine 1m sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone 2a, and also to 5-fluorouracil. A series of compounds was prepared that incorporated some of the molecular features of 2a and related compounds with various N2-acryloylhydrazides in series 1. These compounds are potent cytotoxins. Two modes of action of representative compounds are the lowering of mitochondrial membrane potential and increasing the concentration of reactive oxygen species.

Imaging human skin autograft integration with optical coherence tomography.

BACKGROUND: Skin autografting is a common clinical procedure for reconstructive surgery. Despite its widespread use, very few studies have been conducted to non-invasively evaluate and monitor the vascular and structural features of skin grafts. This study, therefore, aims to demonstrate the potential of optical coherence tomography (OCT) alongside OCT-based angiography (OCTA) to non-invasively image and monitor human skin graft health and integration over time. METHODS: An in-house-built clinical prototype OCT system was used to acquire OCT/OCTA images from patients who underwent split-thickness skin graft surgery following severe burn damage to the skin. The OCT imaging was carried out at multiple locations over multiple time points with a field of view of ~9 mm × 9 mm and a penetration depth of ~1.5 mm. In addition to obtaining high-resolution qualitative images, we also quantitatively measured and compared specific structural and vascular parameters, such as identifiable layer thickness and corresponding vascular area density and diameter. RESULTS: Two patients (patient #1 and #2) were enrolled for this preliminary study. Vascular and structural features were successfully imaged and measured in the graft tissue and integration layer immediately beneath at different time points. Revascularization, healing, and integration were monitored with patient-specific details. Results of the quantitative image analysis from patient #1 indicated that integration layer thickness 16-day post-surgery was significantly less (~50%) than that of 7-day post-surgery. Additionally, with patient #2, significant growth (~20%) was seen with the vascular area density of both the graft and corresponding integration layer beneath between 6 and 14 days post-surgery. CONCLUSIONS: Our preliminary studies show that OCT/OCTA has clinical potential to image and measure numerous features of human skin graft health and integration in the days and weeks following split-thickness surgery. For the first time, we demonstrate the applicability of non-invasive imaging technology for novel clinical uses that could eventually aid in the betterment of surgical practices and clinical outcomes.

An observational study on acceptability, palatability, and safety of Ayurveda immunity booster kit for the prevention of COVID-19 in frontline workers in Jaipur, India.

Background: National Institute of Ayurveda, Jaipur, India, had distributed Ayurveda immunity booster kit (AIBK) (prepared at own pharmacy and comprising Chyawanprasha - 300 g, Vyadhi Kshamatva Kwatha - 300 g, and Vyadhi Kshamatva capsule - 30 g) for 15 days among the health-care workers, sanitation workers, and security and police staff engaged in the containment zones for prevention of COVID-19. Aim: The aim of present study was to explore the medication that may be effective in prevention of the COVID -19. Hence, this study was done to assess the compliance of these medicines and their effects in the prevention of COVID-19. Methods: One thousand seven hundred and fourteen frontline workers were provided with the AIBK for 15 days from April 24, 2020, to June 27, 2020. Data of frontline workers who had participated in AIBK and completed the treatment regimen with 2 weeks of follow-up after treatment with complete available data for safety, palatability, efficacy, and compliance were included in the study. Any adverse event needing hospitalization or medication, drug compliance and palatability, and appearance of the symptoms of COVID-19 or testing positive for COVID-19 were the outcome measures. Results: Out of 1714 participants, 1003 participants were found to be eligible for this analysis. The median age of these participants was 39 years (range, 19-70), and males accounted for 90.1% (904 of 1003). A total of 7.5% of participants (75 of 1003) reported having adverse events after taking the study treatment. None of the participants reported any serious adverse effects after the administration of the AIBK. The acceptability of the AIBK was as high as 97.4%. None of the participants reported positive for COVID-19 results or COVID-19 symptoms up to 2 weeks of follow-up after completion of the study treatment. Conclusion: The acceptability of AIBK is good and indicates its role in the prevention of COVID-19-like illness, hence further randomized control trials or cohort studies can be done to assess the mechanism of action and efficacy of AIBK as the preventive strategy in COVID-19.

Combinatorial Large-Area MoS2/Anatase-TiO2 Interface: A Pathway to Emergent Optical and Optoelectronic Functionalities.

The interface of transition-metal dichalcogenides (TMDCs) and high-k dielectric transition-metal oxides (TMOs) had triggered umpteen discourses because of the indubitable impact of TMOs in reducing the contact resistances and restraining the Fermi-level pinning for the metal-TMDC contacts. In the present work, we focus on the unresolved tumults of large-area TMDC/TMO interfaces, grown by adopting different techniques. Here, on a pulsed laser-deposited MoS2 thin film, a layer of TiO2 is grown by atomic layer deposition (ALD) and pulsed laser deposition (PLD). These two different techniques emanate the layer of TiO2 with different crystallinities, thicknesses, and interfacial morphologies, subsequently influencing the electronic and optical properties of the interfaces. Contrasting the earlier reports of n-type doping at the exfoliated MoS2/TiO2 interfaces, the large-area MoS2/anatase-TiO2 films had realized a p-type doping of the underneath MoS2, manifesting a boost in the extent of p-type doping with increasing thickness of TiO2, as emerged from the X-ray photoelectron spectra. Density functional analysis of the MoS2/anatase-TiO2 interfaces, with pristine and interfacial defect configurations, could correlate the interdependence of doping and the terminating atomic surface of TiO2 on MoS2. The optical properties of the interface, encompassing photoluminescence, transient absorption and z-scan two-photon absorption, indicate the presence of defect-induced localized midgap levels in MoS2/TiO2 (PLD) and a relatively defect-free interface in MoS2/TiO2 (ALD), corroborating nicely with the corresponding theoretical analysis. From the investigation of optical properties, we indicate that the MoS2/TiO2 (PLD) interface may act as a promising saturable absorber, having a significant nonlinear response for the sub-band-gap excitations. Moreover, the MoS2/TiO2 (PLD) interface had exemplified better phototransport properties. A potential application of MoS2/TiO2 (PLD) is demonstrated by the fabrication of a p-type phototransistor with the ionic-gel top gate. This endeavor to analyze and perceive the MoS2/TiO2 interface establishes the prospectives of large-area interfaces in the field of optics and optoelectronics.

Synthetic and computational studies on CuI/ligand pair promoted activation of C(Aryl)-Cl bond in C-N coupling reactions.

Cu/ligand-mediated coupling reactions have been widely investigated in the recent past. However, activation of cheaper aryl chlorides is still a great limitation of these reactions. During the course of present investigations efforts have been made to develop a normal and facile CuI/ligand pair protocol for arylation of phthalimide using aryl chlorides. The protocol has also been extended for arylation of amines. On the basis of experimental and theoretical results, a catalytic cycle has also been proposed and it has been established that these reactions follow oxidative addition-reductive elimination (OA-RE) pathway. These studies have indicated that tetracoordinated [Cu(L1)(L2)]+ complex is active catalytic species in these reactions.

Bilateral Masseter and Internal Pterygoid Muscle Hypertrophy: A Diagnostic Challenge.

OBJECTIVE: To describe an unusual case of bilateral masseter and pterygoid muscle hypertrophy. CLINICAL PRESENTATION AND INTERVENTION: A 23-year-old male patient presented with a bilateral, painless swelling of 1 year duration at the parotid areas without improvement after using antibiotics/systemic corticosteroids/non steroidal anti-inflammatory agents. His medical history was not significant. The initial differential diagnosis included salivary gland/jaw bone/masseter pathology, but the MRI revealed only an increase in the size of the masseter and pterygoid muscles. The patient was informed of the benign nature of the swelling and was advised to discontinue the use of non steroidal anti-inflammatory agents. CONCLUSION: The bilateral hypertrophy of masseter muscles should be considered in differential diagnosis in cases of unilateral or bilateral swelling of the parotid or lateral mandible area.

Heat shock proteins and their expression in primary murine cardiac cell populations during ischemia and reperfusion.

A tight quality control system over protein folding, turnover and synthesis, involving molecular chaperones and co-chaperones, maintains the balance of cardiac proteins. Various cardiac pathologies, including myocardial infarction, increase stresses and post-translational modifications favoring misfolding due to an overwhelmed quality control system. The toxic nature of accumulated misfolded proteins further worsens the condition. The important molecular chaperones which act as quality control proteins are involved in protecting the heart, these include heat shock protein70 (HSP70) and HSP90. Here, we review the emerging roles of heat shock proteins in the maintenance of cardiac cell populations in experimental models of ischemia/reperfusion (I/R) injury. Furthermore, we discuss the expression of HSP70 and HSP90 with therapeutic and diagnostic considerations. Although there is only a partial understanding of these important HSPs in I/R injury, there is an immense therapeutic potential of modulating these HSPs to counteract the imbalance between misfolding and endogenous protein quality control systems.

Engineering protein assemblies with allosteric control via monomer fold-switching.

The macromolecular machines of life use allosteric control to self-assemble, dissociate and change shape in response to signals. Despite enormous interest, the design of nanoscale allosteric assemblies has proven tremendously challenging. Here we present a proof of concept of allosteric assembly in which an engineered fold switch on the protein monomer triggers or blocks assembly. Our design is based on the hyper-stable, naturally monomeric protein CI2, a paradigm of simple two-state folding, and the toroidal arrangement with 6-fold symmetry that it only adopts in crystalline form. We engineer CI2 to enable a switch between the native and an alternate, latent fold that self-assembles onto hexagonal toroidal particles by exposing a favorable inter-monomer interface. The assembly is controlled on demand via the competing effects of temperature and a designed short peptide. These findings unveil a remarkable potential for structural metamorphosis in proteins and demonstrate key principles for engineering protein-based nanomachinery.

Calmodulin-binding proteins: A journey of 40 years.

The proteins which bind to calmodulin in a Ca2+-dependent and reversible manner are known as calmodulin-binding proteins. These proteins are involved in a multitude of processes in which Ca2+ and calmodulin play crucial roles. Our group elucidated the mechanism and importance of these proteins in normal and diseased conditions. Various calmodulin-binding proteins were discovered and purified from bovine tissue including a heat stable calmodulin-binding protein 70, calmodulin-dependent protein kinase VI and a high molecular weight calmodulin-binding protein (HMWCaMBP). We observed a complex interplay occurs between these and other Ca2+ and calmodulin-binding proteins during cardiac ischemia and reperfusion. Purified cardiac HMWCaMBP is a homolog form of calpastatin and an inhibitor of the Ca2+-activated cysteine proteases, calpains and therefore can have cardioprotective role in ischemic conditions. Calcineurin is a Ca2+ and calmodulin-dependent serine/threonine protein phosphatase showed increased phosphatase activity in ischemic heart through its direct interaction with Hsp70 and expression of calcineurin following ischemia suggests self-repair and favorable survival outcomes. Calcineurin was also found to be present in other tissues including the eye; where its expression and calcineurin phosphatase activity varied. In neurons, calcineurin may play a key role in initiating apoptosis-related pathways especially in epilepsy. In colorectal cancer we demonstrated high calcineurin phosphatase activity and simultaneous overexpression of calcineurin. The impact of calcineurin signaling on neuronal apoptosis in epilepsy and its use as a diagnostic marker for colorectal cancer requires in-depth study.

Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model.

Breast cancer is the most common malignancy in women of the Western world. Doxorubicin (DOX) continues to be used extensively to treat early-stage or node-positive breast cancer, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, and metastatic disease. We have previously demonstrated in a mouse model that sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, protects the heart from DOX-induced toxicity and damage. However, the effects of SFN on the chemotherapeutic efficacy of DOX in breast cancer are not known. Present studies were designed to investigate whether SFN alters the effects of DOX on breast cancer regression while also acting as a cardioprotective agent. Studies on rat neonatal cardiomyocytes and multiple rat and human breast cancer cell lines revealed that SFN protects cardiac cells but not cancer cells from DOX toxicity. Results of studies in a rat orthotopic breast cancer model indicated that SFN enhanced the efficacy of DOX in regression of tumor growth, and that the DOX dosage required to treat the tumor could be reduced when SFN was administered concomitantly. Additionally, SFN enhanced mitochondrial respiration in the hearts of DOX-treated rats and reduced cardiac oxidative stress caused by DOX, as evidenced by the inhibition of lipid peroxidation, the activation of NF-E2-related factor 2 (Nrf2) and associated antioxidant enzymes. These studies indicate that SFN not only acts synergistically with DOX in cancer regression, but also protects the heart from DOX toxicity through Nrf2 activation and protection of mitochondrial integrity and functions.

Reduced Expression of Glutathione S-Transferase α 4 Promotes Vascular Neointimal Hyperplasia in CKD.

Neointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)-mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs. Compared with non-CKD controls, mice with CKD had downregulated expression of GSTA4 at the mRNA and protein levels, with concomitant increase in 4-HNE in arteries and veins. This effect was associated with upregulated phosphorylation of MAPK signaling pathway proteins in proliferating SMCs. Overexpressing GSTA4 blocked 4-HNE-induced SMC proliferation. Additionally, inhibitors of MAPK signaling inhibited the 4-HNE-induced responses. Compared with wild-type mice, mice lacking GSTA4 exhibited increased CKD-induced neointima formation in AVF. Transient expression of an activated form of GSTA4, achieved using a combined Tet-On/Cre induction system in mice, lowered levels of 4-HNE and reduced the proliferation of SMCs. Together, these results demonstrate the critical role of GSTA4 in blocking CKD-induced neointima formation and AVF failure.

Interplay between the folding mechanism and binding modes in folding coupled to binding processes.

Proteins that fold upon binding to their partners exhibit complex binding behavior such as induced-fit. But the connections between the folding mechanism and the binding mode remain unknown. Here we focus on the high affinity complex between the physiologically and marginally unstable, fast folder PSBD and the E1 subunit of pyruvate dehydrogenase. Using coarse-grained simulations we investigate the binding to E1 of a partially disordered PSBD under two folding scenarios: two-state and downhill. Our simulations show that induced-fit binding requires that PSBD folds-unfolds in the downhill folding regime. In contrast, a two-state folding PSBD must fold completely before it binds. The reason is that effective coupling between folding and binding involves partially folded conformations, which are only sufficiently populated under the downhill folding regime. Our results establish a direct mechanistic link between complex binding and downhill folding, supporting the idea that PSBD operates functionally as a conformational rheostat.

Introducing structured viva voce examination in medical undergraduate pharmacology: A pilot study.

OBJECTIVE: Viva voce examination is an important tool of evaluation in medical examinations marred by high subjectivity. Gross subjectivity in viva voce assessment can be reduced by structuring it. MATERIALS AND METHODS: The marks obtained in theory and viva voce (traditional viva voce examination [TVVE]) of I sessional, II MBBS students were compared and a huge disparity was identified. A structured viva voce examination (SVVE) was then proposed and experimented as an objective and standardized alternative. Sets of equitable question cards for SVVE were prepared, each having eight questions with two parts each, arranged successively with increasing difficulty, domains of learning, and appropriate marks. The percentage variation in scoring in viva versus theory marks was calculated for both TVVE and SVVE, and students were grouped as Group I (+100 to +51%); Group II (+50 to -50%); Group III (-51 to -100%); Group IV (-101 to -150%); Group V (-151 to -200%); and Group VI (< -200%) variation, as? inappropriate, appropriate, inappropriate, erroneous, more erroneous and most erroneous respectively. Student's feedback on the SVVE was also obtained. RESULTS: In TVVE (n = 128), the students distributed were:none,17.2%, 23.4%, 22.7%, 11.7% and 25% in Group I, II, III, IV, V, and VI in contrast to SVVE (n = 107) as 7.5%, 57.9%, 19.6%, 6.5%, 5.6%, and 2.8%, respectively. Marked disparity of TVVE was annulled with SVVE. Student's feedback was quite encouraging with 83% overall acceptability and almost 66% preferred SVVE. CONCLUSION: SVVE was more realistic as compared to TVVE. Most of the students favored this approach.

Insulin Cannot Induce Adipogenic Differentiation in Primary Cardiac Cultures.

Cardiac tissue contains a heterogeneous population of cardiomyocytes and nonmyocyte population especially fibroblasts. Fibroblast differentiation into adipogenic lineage is important for fat accumulation around the heart which is important in cardiac pathology. The differentiation in fibroblast has been observed both spontaneously and due to increased insulin stimulation. The present study aims to observe the effect of insulin in adipogenic differentiation of cardiac cells present in primary murine cardiomyocyte cultures. Oil Red O (ORO) staining has been used for observing the lipid accumulations formed due to adipogenic differentiation in murine cardiomyocyte cultures. The accumulated lipids were quantified by ORO assay and normalized using protein estimation. The lipid accumulation in cardiac cultures did not increase in presence of insulin. However, addition of other growth factors like insulin-like growth factor 1 and epidermal growth factor promoted adipogenic differentiation even in the presence of insulin and other inhibitory molecules such as vitamins. Lipid accumulation also increased in cells grown in media without insulin after an initial exposure to insulin-containing growth media. The current study adds to the existing knowledge that the insulin by itself cannot induce adipogenic induction in the cardiac cultures. The data have significance in the understanding of cardiovascular health especially in diabetic patients.