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Exploring new synthetic methods that harness visible light represents a breakthrough in organic synthesis. Amides, amines, nitriles, and halides are essential functional groups and serve as key building blocks in the synthesis of complex molecules in organic and medicinal chemistry. This study introduces a novel intermolecular benzylic C-X (C-N, C-C, and C-Br) bond formation via photoredox benzylic C(sp 3 )-H bonds. This methodology enables the synthesis of secondary amides, nitriles, and halides through reacting secondary benzylic substrates with readily accessible reagents including BocNH 2 , benzamide, acetamide, TMSCN, and TBAB. This approach displays the potential of being sustainable and efficient to afford amidation, cyanation, and halogenation products in good yields.

Background: Gallbladder cancer (GBC) is a rare, highly fatal disease with diagnosis in advanced stage and low survival rate. Nepal ranked 4th position with highest rates of GBC for 10 countries in 2020., Objective: To find the association between socio-demographic, behavioral and environmental factors associated with the development of GBC., Method: A case-control study was conducted in 2021/22 with newly diagnosed gallbladder cancer cases from three cancer-specialized hospitals and one tertiary (superspeciality) hospital. Controls were selected from the same tertiary hospital and one additional hospital providing services to gallbladder pathologies for a huge population, making a total of five hospitals involved in the study. The ratio of cases to control was 1:1. The data collection was done through telephonic interviews using structured questionnaires. The risk factors for GBC were assessed by using unconditional logistic regression to find odds ratios and 95% confidence level for bivariate and multivariate analysis. The statistical analysis was carried out in STATA 18., Result: A total of 240 respondents were enrolled in the study, among them half were GBC patients (cases) and half were gallbladder patients (controls). The average age of the respondents was 54.82±12.3 years, with female preponderance among both groups. On multivariate analysis, the risk factors studied were; parity ≥3 (AOR = 2.80, 95% CI: 1.17-6.66, P value 0.020), being ethnic group of Terai/Madhesi (AOR = 7.88, 95% CI: 3.16-19.66, P value <0.001), being Janajati (AOR = 3.36, 95% CI: 1.17-6.61, P value <0.001), having gallbladder related disease (AOR = 2.00, 95% CI:1.00-4.02, P value 0.049), consuming alcohol ≥100ml/day (AOR = 3.44, 95% CI:1.11-10.63, P value 0.032), exposed with pesticides ≥2 times in a year (AOR = 4.04, 95% CI: 1.27-12.89, P value 0.018) and consuming less vegetables and fruits (<1 times per day in a week) (AOR = 2.69, 95% CI:1.34-5.40, P value 0.005)., Conclusion: The study reveals key GBC risk factors, offering vital insights for targeted screening, resource allocation, and public health measures to mitigate risks in Nepal., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Thakur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Metastatic progression significantly reduces survival rates and complicates treatment strategies in various cancers. Our study introduces an mRNA therapy for metastasis inhibition by targeting activin A overexpression, a pivotal driver of metastasis and cachexia. Utilizing follistatin mRNA lipid nanoparticles, we effectively downregulated activin A both locally in the tumor environment and systemically. This led to a reduction in tumor burden and suppression of metastatic spread in a murine head and neck squamous cell carcinoma model. Treated mice exhibited minimal metastatic occurrence compared to controls. Additionally, our therapy preserved the cross-sectional area of muscle fibers and adipose tissues, combating the muscle and fat wasting typically observed in cancer-associated cachexia. The therapy also demonstrated a favorable safety profile, underscoring its potential for clinical translation. By integrating metastasis-suppressing and cachexia-alleviating mechanisms, our approach represents a promising advancement in comprehensive cancer management. Considering the widespread upregulation of activin A in many cancer types, our therapy holds considerable potential for application across a broad spectrum of oncologic treatments.

There is great interest in fabricating devices that can detect and remove water pollutants, especially heavy metal ions and dyes from wastewater, to promote sustainable water use. In this study, an extract of Borassus flabellifer leaves (BoF-LE) was used to synthesize silver nanoparticles (BoF-AgNPs), with the BoF-LE serving as a reducing and capping agent. The sensitivity and selectivity of BoF-AgNPs for Mn(II) ions were tested by comparing with the control sample and other competent metal ions. Our results showed that BoF-AgNPs are extremely sensitive and selective in detecting Mn(II) ions, with a detection limit of 0.3 ppb. HR-TEM, UV-Vis spectroscopy, and DLS investigations were used to confirm that BoF-AgNPs detect Mn(II) ions by an aggregation-based mechanism. Additionally, it was found that BoF-AgNPs are effective in rapidly decolorizing MB dye, as demonstrated by their ability to decolorize MB by 92.66% within 7 min. This study is the first to report successful synthesis of BoF-AgNPs and their two applications, which are enabled with an Inhibit-AND logic gate. Using BoF-AgNPs to detect and degrade water pollutants may promote sustainable water use., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kritika S. Sharma reports financial support was provided by Department of Science and Technology (DST), Ministry of Science & Technology, India. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

mRNA therapeutics encapsulated in lipid nanoparticles (LNPs) offer promising avenues for treating various diseases. While mRNA vaccines anticipate immunogenicity, the associated reactogenicity of mRNA-loaded LNPs poses significant challenges, especially in protein replacement therapies requiring multiple administrations, leading to adverse effects and suboptimal therapeutic outcomes. Historically, research has primarily focused on the reactogenicity of mRNA cargo, leaving the role of LNPs understudied in this context. Adjuvanticity and pro-inflammatory characteristics of LNPs, originating at least in part from ionizable lipids, may induce inflammation, activate toll-like receptors (TLRs), and impact mRNA translation. Knowledge gaps remain in understanding LNP-induced TLR activation and its impact on induction of animal sickness behavior. We hypothesized that ionizable lipids in LNPs, structurally resembling lipid A from lipopolysaccharide, could activate TLR4 signaling via MyD88 and TRIF adaptors, thereby propagating LNP-associated reactogenicity. Our comprehensive investigation utilizing gene ablation studies and pharmacological receptor manipulation proves that TLR4 activation by LNPs triggers distinct physiologically meaningful responses in mice. We show that TLR4 and MyD88 are essential for reactogenic signal initiation, pro-inflammatory gene expression, and physiological outcomes like food intake and body weight─robust metrics of sickness behavior in mice. The application of the TLR4 inhibitor TAK-242 effectively reduces the reactogenicity associated with LNPs by mitigating TLR4-driven inflammatory responses. Our findings elucidate the critical role of the TLR4-MyD88 axis in LNP-induced reactogenicity, providing a mechanistic framework for developing safer mRNA therapeutics and offering a strategy to mitigate adverse effects through targeted inhibition of this pathway.

A precision measurement of the β^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the β-ν angular correlation coefficient a&#95;{βν}. The experimental results were combined with new ab initio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a&#95;{βν}=-0.3345±0.0019&#95;{stat}±0.0021&#95;{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision β decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

Persistent and uncontrolled inflammation is the root cause of various debilitating diseases. Given that interleukin-1 receptor-associated kinase 4 (IRAK4) is a critical modulator of inflammation, inhibition of its activity with selective drug molecules (IRAK4 inhibitors) represents a promising therapeutic strategy for inflammatory disorders. To exploit the full potential of this treatment approach, drug carriers for efficient delivery of IRAK4 inhibitors to inflamed tissues are essential. Herein, the first nanoparticle-based platform for the targeted systemic delivery of a clinically tested IRAK4 inhibitor, PF-06650833, with limited aqueous solubility (57 µg mL -1 ) is presented. The developed nanocarriers increase the intrinsic aqueous dispersibility of this IRAK4 inhibitor by 40 times. A targeting peptide on the surface of nanocarriers significantly enhances their accumulation after intravenous injection in inflamed tissues of mice with induced paw edema and ulcerative colitis when compared to non-targeted counterparts. The delivered IRAK4 inhibitor markedly abates inflammation and dramatically suppresses paw edema, mitigates colitis symptoms, and reduces proinflammatory cytokine levels in the affected tissues. Importantly, repeated injections of IRAK4 inhibitor-loaded nanocarriers have no acute toxic effect on major organs of mice. Therefore, the developed nanocarriers have the potential to significantly improve the therapeutic efficacy of IRAK4 inhibitors for different inflammatory diseases., (© 2023 Wiley-VCH GmbH.)

Nuclear isomer effects are pivotal in understanding nuclear astrophysics, particularly in the rapid neutron-capture process where the population of metastable isomers can alter the radioactive decay paths of nuclei produced during astrophysical events. The β-decaying isomer ^{128m}Sb was identified as potentially impactful since the β-decay pathway along the A=128 isobar funnels into this state bypassing the ground state. We report the first direct mass measurements of the ^{128}Sb isomer and ground state using the Canadian Penning Trap mass spectrometer at Argonne National Laboratory. We find mass excesses of -84564.8(25)  keV and -84608.8(21)  keV, respectively, resulting in an excitation energy for the isomer of 43.9(33) keV. These results provide the first key nuclear data input for understanding the role of ^{128m}Sb in nucleosynthesis, and we show that it will influence the flow of the rapid neutron-capture process.

Background: Psoriasis is an acute to chronic multifunctional inflammatory skin disorder mediated through T-cell activation, dendritic cell intervention, local vascular variations, atypical keratinocyte proliferation, and neutrophil activation, leading to a skin disorder with no permanent cure., Objective: This review aims to find a potent, secure, and dependable medication, with a more scientific examination of herbal resources and recent targeted immunobiological therapies., Method: Reports evaluating the effectiveness of biologics & herbal remedies for the topical therapy of psoriasis against control therapies were taken into consideration (placebo or active therapy). The work examined cellular circuits involved in inflammation with its immunogenetic mechanism behind various options available for treating psoriasis in addition to the role of agents inducing psoriasis., Results: The extent of psoriasis can range from small, localized spots to total body coverage, and it can happen at any stage of life. Several theories exist for clarification however, the exact cause of psoriasis is not entirely understood. Researchers have discovered genetic loci linkages, environmental changes, drug induction, lifestyle conditions, some infections, etc. resulting in this disorder. There are numerous known conventional medical treatments for psoriasis, ranging from topical and systemic medicines to phototherapy or combinations of both with recent immunobiological treatment. However, the majority of these treatments are ineffective and have a variety of side effects that limit their long-term usage, such as cutaneous atrophy, tissue toxicity, mutagenicity, and immunosuppression., Conclusion: Herbal extracts or isolated compounds can be considered as a substitute for conventional psoriasis treatment. Unfortunately, many investigations often provide a small amount of facts about the safety and effectiveness of topically applied herbal remedies for the treatment of psoriasis. Thus, further factual evidences and validations are needed to promote herbal options, which must be supported by rigorous animal studies or clinical trials using standardised materials and compositions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A new method to determine the make and model of a vehicle from an automotive paint sample recovered at the crime scene of a vehicle-related fatality such as a hit-and-run using Raman microscopy has been developed. Raman spectra were collected from 118 automotive paint samples from six General Motors (GM) vehicle assembly plants to investigate the discrimination power of Raman spectroscopy for automotive clearcoats using a genetic algorithm for pattern recognition that incorporates model inference and sample error in the variable selection process. Each vehicle assembly plant pertained to a specific vehicle model. The spectral region between 1802 and 697 cm -1 was found to be supportive of the discrimination of these six GM assembly plants. By comparison, only one of the six automotive assembly plants could be differentiated from the other five assembly plants using Fourier transform infrared spectroscopy (FT-IR), which is the most widely used analytical method for the examination of automotive paint) and the genetic algorithm for pattern recognition. The results of this study indicate that Raman spectroscopy in combination with pattern recognition methods offers distinct advantages over FT-IR for the identification and discrimination of automotive clearcoats.

Background and Aims: A variety of extraglottic airway devices (EADs) are available. Main concerns with EADs are protection against aspiration and ability to ventilate patients with high airway pressures. Baska mask meets these criteria and is the only third-generation device available for clinical use., Methods: After institutional ethics committee approval and informed consent were obtained, this prospective study was performed in 100 adult patients undergoing surface surgeries at a tertiary referral centre. The primary outcome was the success rate of insertion, while the secondary outcomes were the sealing pressure, stability of the device and the perioperative complications of Baska mask. We then compared it with other currently used EADs., Results: The first attempt at insertion and overall success rates, showed values of 81% and 98%, respectively. Insertion was quick (median 12; interquartile range [IQR] 9-15 s). The mask sealing pressure, was 35 cmH 2 O (median [IQR 20-50 cmH 2 O]). Also, the mask remained stable in 95% of patients intraoperatively. Sore throat and dysphagia were seen in 37% and 24% of patients, respectively. No patient had laryngospasm or desaturation at any time. It compared favourably well with other EADs, while achieving higher sealing pressures., Conclusion: We found that the Baska mask performs well with excellent first attempt at insertion and overall success rates, higher sealing pressures and minimal complications compared to currently used EADs in clinical anaesthesia., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

Diarylheptanoids are a major class of plant secondary metabolites characterized by 1, 7-diphenyl heptanes in a seven-member carbon frame. In the present study, diarylheptanoids (garuganins 1, 3, 4 and 5) isolated from Garuga pinnata stem bark were evaluated for cytotoxic activity against MCF-7 and HCT15 cancer cell lines. Among the tested compounds, garuganin 5 and 3 exhibited the highest cytotoxic activity against HCT15 and MCF-7 with IC 50 2.9 ± 00.8 μg/mL, 3.3 ± 0.1 μg/mL and 3.2 ± 0.1 μg/mL, and 3.5 ± 0.3 μg/mL, respectively. The molecular docking of garuganin 1, 3, 4 and 5 exhibited significant affinity toward the tested EGFR 4Hjo protein. The free energy and inhibitory constant of the compounds ranged from - 7.47 to - 8.49 kcal/mol and 3.34 micromolar to 944.20 nM nanomolar, respectively. Based on the results of cytotoxic activity, garuganin 5 and 3 were further evaluated for time- and concentration-dependent intracellular accumulation studies. The time-dependent intracellular concentration of garuganin 3 and 5 after 5 h of incubation increased about 5.5- and 4.5-fold, 204.16 ± 0.02 and 145.4 ± 0.36 nmol/L mg, respectively. The concentration-dependent intracellular concentration of garuganin 3 and 5 at 200 µg/mL increased of about > 12- and ninefold, 186.22 ± 0.05 and 98.73 ± 0.02 nmol/L mg, respectively. The intracellular concentrations of garuganin 3 and 5, in the presence of verapamil, cyclosporine and MK 571, was found to be significant in the basal direction compared to the apical directions. The results indicate that, garuganin 3 and 5 exhibited significant cytotoxic activity against MCF-7 and HCT15 cancer cell lines and also exhibited high binding affinity toward EGFR protein compared to garuganin 1 and 4., Competing Interests: Conflict of interestThe authors disclose no conflict of financial or nonfinancial interest.Ethical statementsThe authors do not have any potential conflict of interest. This study does not involve any human beings or animals., (© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

We present the first measurement of the α-β-ν angular correlation in the Gamow-Teller β^{+} decay of ^{8}B. This was accomplished using the Beta-decay Paul Trap, expanding on our previous work on the β^{-} decay of ^{8}Li. The ^{8}B result is consistent with the V-A electroweak interaction of the standard model and, on its own, provides a limit on the exotic right-handed tensor current relative to the axial-vector current of |C&#95;{T}/C&#95;{A}|^{2}<0.013 at the 95.5% confidence level. This represents the first high-precision angular correlation measurements in mirror decays and was made possible through the use of an ion trap. By combining this ^{8}B result with our previous ^{8}Li results, we demonstrate a new pathway for increased precision in searches for exotic currents.

The role of mechanical thrombectomy (MT) in cerebral venous sinus thrombosis (CVT) is ambiguous. This study aims to share our experience with MT in CVT, supplemented by a meta-analysis on this treatment. All patients who had MT for CVT at our institution, between 2016 and 2021, were retrospectively reviewed for treatment indications, the technique used, success and complication rates, and clinical outcomes. A meta-analysis was performed for clinical and safety outcomes from published literature with > 10 patients. A total of 15 patients were included in this study. All had a venous hemorrhage or deteriorating despite anticoagulation. MT was performed using aspiration (with wide bore catheters) in 7 patients: aspiration with stent retriever in 5 and transjugular Fogarty-balloon thrombectomy in 3 patients. Adjunctive intra-sinus thrombolysis (IST) was used in 4 cases and venoplasty in 3. Technical success (restoring antegrade venous flow on arterial injection) was 100% with no procedure-related major complication. The direct transjugular approach was cheaper and faster. At 3-month follow-up, 86% of patients had good outcomes (MRS < 2). Meta-analysis of clinical and safety outcomes from 22 and 20 studies, respectively, demonstrated a positive association between MT and good outcomes as well as no significant association with hazardous periprocedural events. EVT via mechanical means for CVT is feasible in our series and meta-analysis. From our experience, trans-jugular Fogarty balloon embolectomy seems to be a potential cost-saving option, at least in a certain part of the world., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Deoxyglucose conjugated nanoparticles with persistent luminescence have shown theragnostic potential. In this study, deoxyglucose-conjugated nano-particles with persistent luminescence properties were synthesized, and their theragnostic potential was evaluated in fibrosarcoma cancer cells and a tumor model. The uptake of nano-formulation was found to be higher in mouse fibrosarcoma (WEHI-164) cells cultured in a medium without glucose. Nanoparticles showed a higher killing ability for cancer cells compared to normal cells. A significant accumulation of nanoparticles to the tumor site in mice was evident by the increased tumor/normal leg ratio, resulting in a significant decrease in tumor volume and weight. Histopathological studies showed a significant decrease in the number of dividing mitotic cells but a greater number of apoptotic/necrotic cells in nanoparticle-treated tumor tissues, which was correlated with a lower magnitude of Ki-67 expression (a proliferation marker). Consequently, our results showed the potential of our nano-formulation for cancer theragnosis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report herein a redox neutral visible light-induced regioselective C(sp 2 )-H imidation of electron-rich arenes and heteroarenes using conceptually designed redox-active 1 as a source of the N-centered imidyl radical. Structurally diverse aromatic imides were obtained in moderate to good yields. This methodology has been successfully employed for the late stage imidation of complex molecules and has also been applied towards the formal total synthesis of the marine natural products carpatamides A, B and D. It has further been shown that the generated imides can easily be converted to the corresponding anilines in situ directly.

5D & 4D printings are an advanced version of 3D printing class and are one of the most revolutionary and powerful fabrication methods used for preparing innovative structures and solid substances using precise additive manufacturing technology. It captures the imagination of one with its potential to produce flexible designing and fabrication of innovative products with high complexity and speed. This technology with the assistance of AI (Artificial Intelligence) facilitates real-time sensing, adapting to change, and predicting the state of printing. 3D printing works by employing advanced materials utilizing a computer aided design with tomography scan under AI control which deposits printing material in accordance with the nature of a file usually in STL format, but it requires time for printing. This shortcoming can be overcome by 4D printing where smart materials are incorporated with time as 4th dimension. This technique has self-repair and self-assembly properties that will save around 80% of time. Some printed materials are made sensitive to temperature, humidity, light, and other parameters so that they can respond to stimulus, but it's one limitation of not being able to print complex shapes having curved surfaces can be overcome by utilising 5D printing where additive manufacturing is done by rotation of extruder head and rotation of print bed to print in 5 different axes. This review evaluates the prospective of these techniques with AI interference in medicine and pharmacy, with its effective and efficient production for the required design precision., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Human species is confronting with a gigantic global COVID-19 pandemic. Initially, it was observed in Wuhan, China, and the COVID-19 cases spread across the globe with lightning speed and resulted in the 21st century pandemic. If scientific reports are taken care of, it is noteworthy that this virus possesses more specific characteristics due to its structure. The distinctive structure has a higher binding affinity with angiotensin-converting enzyme 2 (ACE2) protein, and this is used as an access point to gain access to hosts., Methods: A complete literature search was conducted using PubMed, Google Scholar, SciFinder, and deep-diving Google Search using keywords such as "Pregnancy, COVID-19, Newborn, Fetus, Coronavirus 2019, Neonate, Pregnant women, and vertical transmission"., Result and Discussion: The SARS-CoV-2 virus is unlike its former analogs: SARS-CoV, and MERS-CoV in 2002 and 2012, respectively, or anything mankind has faced earlier concerning viciousness, global spread, and gravity of a causative agent. The current review has delved into articles published in various journals worldwide including the latest studies on the impact of COVID-19 on pregnant women and neonates and has discussed complications and challenges, psychological health, immunological response, vertical transmission, concurrent disorders, vaccine debate, management recommendations, recent news of the approval of COVID-19 vaccine for 6 months and older babies, and future perspectives., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s). Published by Elsevier Ltd.)

A large-scale mortality of pearlspot, Etroplus suratensis was reported from Peechi Dam, an artificial tropical lake made for irrigation and drinking water supply in Kerala, India during 2018. This dam is located in the premises of Western Ghats, recognized as one of the biodiversity hotspots of the world. The objective of this study was to identify the aetiological agent of this large-scale mortality of E. suratensis by systematic diagnostic investigation and identification of the pathogen. Virus isolation was carried out on a species-specific pearlspot fin (PSF) cell line. Infected PSF cells showed cytopathic effects (CPEs) like cell shrinkage, rounding, enlargement, clustering, and subsequent detachment of cells with a high viral titre of 10 6⋅95 TCID 50 ml -1 at 8 days post-inoculation (dpi). Histopathological examination of the fish showed the presence of numerous abnormal enlarged basophilic cells and intracytoplasmic eosinophilic inclusions in the liver. Moreover, transmission electron microscopy (TEM) analysis revealed the presence of large numbers of 125-132 nm viral particles in the spleen tissues. PCR amplification and phylogenetic analysis of the major capsid protein (MCP) gene sequence confirmed that the causative agent was infectious spleen and kidney necrosis virus (ISKNV) of the genus Megalocytivirus. The experimental infection recorded 86.7 ± 2.7% mortality in the E. suratensis (body weight 11.01 ± 2.7 g; body length 8.01 ± 2.23 cm) injected with 1 × 10 4⋅25 TCID 50 ml -1 ISKNV per fish. Our detailed investigation provided definitive diagnosis of ISKNV in the severe mass mortality event in wild E. suratensis in Peechi Dam, India, adding one more species to expanding host range of ISKNV infection. The high mortality rate of ISKNV infection in pearlspot suggests the perilous nature of this disease, particularly among the wild fish population., (© 2022 Wiley-VCH GmbH.)

On the basis of the boron neutron capture therapy (BNCT) modality, we have designed and synthesized a zinc gallate (ZnGa 2 O 4 )-based nanoformulation for developing an innovative theranostic approach for cancer treatment. Initially, the (ZnGa 1.995 Cr 0.005 O 4 or ZnGa 2 O 4 :(0.5%)Cr persistent luminescence nanoparticles (PLNPs) embedded on silica matrix were synthesized. Their surface functionalization was performed using organic synthesis strategies to attach the amine functional moieties which were further coupled with poly(vicinal diol). These diols were helpful for conjugation with 10 B(OH) 3 , which subsequently served to couple with an in-house-synthesized variant of pH-(low)-insertion peptide (pHLIP) finally giving a tumor-targeting nanoformulation. Most importantly, the polymeric diols helped in conjugation of a substantial number of 10 B to provide the therapeutic dose required for effective BNCT. This nanoformulation internalized substantially (∼80%) to WEHI-164 cancer cells within 6 h. Tumor homing studies indicated that the accumulation of this formulation at the acidic tumor site was within 2 h. The in vitro evaluation of the formulation against WEHI-164 cancer cells followed by neutron irradiation revealed its potent cytotoxicity with IC 50 ∼ 25 μM. In the case of studies on animal models, the melanoma-induced C57BL/6 and fibrosarcoma-induced BALB/c mice were treated with formulations through intratumoral and intravenous injections, respectively, followed by neutron irradiation, leading to a significant killing of the cancer cells, which was evidenced by a reduction in tumor volume (75-80%) as compared with a control tumor. Furthermore, the histopathological studies confirmed a damaging effect only on tumor cells, while there was no sign of damage to the vital organs in treated mice as well as in controls.

The electroweak interaction in the standard model is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this Letter, we present the most precise measurement of tensor currents in the low-energy regime by examining the β-ν[over ¯] correlation of trapped ^{8}Li ions with the Beta-decay Paul Trap. We find a&#95;{βν}=-0.3325±0.0013&#95;{stat}±0.0019&#95;{syst} at 1σ for the case of coupling to right-handed neutrinos (C&#95;{T}=-C&#95;{T}^{'}), which is consistent with the standard model prediction.

Exclusively red-emitting upconversion nanoparticles (UCNPs) with the composition NaErF 4 :0.5%Tm as a core and NaYF 4 as a shell were synthesized for performing photodynamic therapy (PDT). A possible mechanism was proposed for core-shell UCNPs formation. For loading a maximum amount of 5-aminolevulinic acid (5-ALA), mesoporous silica coating was performed on UCNPs. Studies under dark conditions confirmed the biocompatibility of 5-ALA-loaded UCNPs formulation (UCNPs-5-ALA) with MCF-7 cells. Meanwhile, studies under light-exposed conditions exhibited effective cytotoxicity against MCF-7 cells. Studies employing D 2 O-based cell cultured media and addition of DABCO in cell culture established that the cell death was due to oxidation of cellular components by reactive oxygen species (ROS) triggering the apoptosis. The formation of ROS was confirmed by DCF( H )DA-based ROS analysis via fluorescence microscopy to demonstrate the ROS production, which mediates the programmed cell death. Additionally, we have validated the apoptosis in MCF-7 cells with flow cytometry analyses. This was further confirmed by an electrophoretic mobility shift assay on nuclear extract and measurement of mitochondrial membrane potential. In the case of animal model studies, the formulation UCNPs-5-ALA without irradiation (980 nm) did not possess any in vivo cytotoxicity on tumor-induced SCID mice and there was a minimum migration of UCNPs-5-ALA to the vital organs but maximum retention at the tumor site only. Meanwhile, only the mice treated with UCNPs-5-ALA and irradiated on the tumor region with 980 nm laser (500 mW) for 20 min possessed a tumor with a size reduced to about 75% as compared with the corresponding control groups. To the best of our knowledge, this type of study was conducted for the first time employing exclusively red-emitting phosphors for effective PDT.

There is a significant interest to develop sensing devices that detect water toxins, especially heavy metal ions. Although there have already been numerical reports on detecting toxic heavy metal ions, the use of adaptable devices could enable a broader range of sensing applications. Here, we used fresh peel extract (PeA) and dried peel extract (DPeA) of Persea americana (Avocado) as a reducing and capping agent to synthesize and stabilize AgNPs. The dimensions of NPs were controlled by tuning pH, temperature, and volume of the reducing agent. The sensitivity and selectivity of the AgNPs toward various metal ions viz. Ni(II), Cd(II), Al(III), Hg(II), Cr(III), Ba(II), Pb(II), Zn(II), Co(II), Mn(II), Cu(II), Ca(II), Mg(II), and K(I) were studied. The detection probe was found to be selective and sensitive toward Al(III) and Cr(III) ions with the detection limit of 0.04 ppm and 0.05 ppm, respectively. High-resolution transmission electron microscope (HRTEM), ultraviolet-visible (UV-Vis) spectroscopy, and dynamic light scattering (DLS) analysis results confirm an agglomeration-based mechanism for sensing both metal ions. This method can be exploited for the colorimetric detection of toxic heavy metals in real water samples.

Tilapia lake virus (TiLV) and Lactococcus garvieae are 2 major pathogens of cultured Nile tilapia Oreochromis niloticus. In June-July 2018, a disease outbreak was reported in Nile tilapia cultured in brackish water floating cages in Kerala, India. Affected fish died gradually, and cumulative mortality reached ~75% within 1 mo. In the present study, TiLV and L. garvieae were isolated from the infected fish and confirmed. Nucleotide analysis of the partial sequence of segment 3 revealed that the present TiLV isolate showed 100% similarity with TiLV MF574205 and 97.65% similarity with TiLV KU552135 isolated in Israel. The partial 16S rDNA nucleotide sequence of L. garvieae shared 99% similarity with the 16S rDNA nucleotide sequence of L. garvieae isolated from Nile tilapia in Brazil. Eight virulence genes (hly1, hly2, hly3, NADH oxidase, adhPav, LPxTG-1, LPxTG-4, adhC1) were amplified in the present isolate. In the experimental challenge study, the onset of mortality started earlier in fish co-infected with TiLV and L. garvieae (3 d post-infection [dpi]) compared to other groups. Cumulative mortality (90% at 12 dpi) was significantly higher in the co-infected group than in fish infected with TiLV (60% at 12 dpi) and L. garvieae (40% at 12 dpi) alone. This study reveals that synergistic co-infection with TiLV and other bacteria may increase mortality in disease outbreaks. To the best of our knowledge, this is the first reported co-infection of L. garvieae with TiLV associated with mass mortality in Nile tilapia in India.

Swellable polymer microspheres that respond to pH were prepared by free radical dispersion polymerization using N -isopropylacrylamide (NIPA), N , N ' -methylenebisacrylamide (MBA), 2,2-dimethoxy-2-phenylacetylphenone, N -tert-butylacrylamide (NTBA), and a pH-sensitive functional comonomer (acrylic acid, methacrylic acid, ethacrylic acid, or propacrylic acid). The diameter of the microspheres was between 0.5 and 1.0 μm. These microspheres were cast into hydrogel membranes prepared by mixing the pH-sensitive swellable polymer particles with aqueous polyvinyl alcohol (PVA) solutions followed by crosslinking with glutaric dialdehyde for use as pH sensors. Large changes in the turbidity of the PVA membrane were observed as the pH of the buffer solution in contact with the membrane was varied. These changes were monitored by UV-visible absorbance spectroscopy. Polymer swelling of many NIPA copolymers was reversible and independent of the ionic strength of the buffer solution in contact with the membrane. Both the degree of swelling and the apparent pK a of the polymer microspheres increased with temperature. Furthermore, the apparent pK a of the polymer particles could be tuned to respond sharply to pH in a broad range (pH 4.0-7.0) by varying the amount of crosslinker (MBA) and transition temperature modifier (NTBA), and the amount, pK a , and hydrophobicity of the pH-sensitive functional comonomer (alkyl acrylic acid) used in the formulation. Potential applications of these polymer particles include fiber optic pH sensing where the pH-sensitive material can be immobilized on the distol end of an optical fiber.

Rosai-Dorfman disease is referred to as sinus histiocytosis massive lymphadenopathy. We are reporting a rare case of Rosai-Dorfman disease, a case of 6-year-old boy with a history of multiple painless submandibular and cervical lymphadenopathy., Competing Interests: All other authors declare that they have no competing interests concerning the content published in this manuscript., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background Aims and Objectives: Cisplatin is extensively used in chemotherapy for treatment of a broad range of cancers. But its undesired side reactions with biomolecules that lead to severe side effects especially on kidney and nervous system, are limiting its clinical utility. To reduce its side effects, the kinetically inert Pt(IV) prodrug was recognized as an alternative approach from satisfactory results of preliminary experiments. But, its approval as anticancer drug for clinical use requires detailed investigations of its anticancer action and pharmacological pathways by employing its analogue which can be traced by a suitable technique. As a step closer towards translation of Pt(IV)-based prodrug from research to clinical level, a protocol for efficient synthesis of 195m Pt-radiolabeled Pt(IV) prodrug was devised., Materials and Methods: In order to achieve the aim, we started synthesis from elemental platinum avoiding lengthy steps. The synthesis protocol was standardized on its cold analogue, as [PtCl 2 (NH 3 ) 2 (OCOCH 2 CH 2 COOH) 2 ] which has been characterized with nuclear magnetic resonance ( 1 H, 13 C{1H} and 195 Pt{1H}) spectroscopy, microanalyses and cyclic voltammetry. Also, cytotoxicity of [PtCl 2 (OCOCH 2 CH 2 COOH) 2 (NH 3 ) 2 ] was evaluated against MCF-7 human breast cancer cell lines using cisplatin as test control., Results: Intrinsically, 195m Pt-labeled analogue of prodrug was obtained with high radionuclidic and radiochemical purity. It was confirmed by chromatography and γ-ray spectrometry., Conclusion: The 195m Pt-radiolabeled prodrug was synthesized in a facile manner. It can be utilized in evaluating the mechanism of anticancer action and pharmacokinetics by enabling synergistic use of molecular imaging and targeted drug delivery., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Nuclear Medicine.)

Background: Single-cell (sc) sequencing performs unbiased profiling of individual cells and enables evaluation of less prevalent cellular populations, often missed using bulk sequencing. However, the scale and the complexity of the sc datasets poses a great challenge in its utility and this problem is further exacerbated when working with larger datasets typically generated by consortium efforts. As the scale of single cell datasets continues to increase exponentially, there is an unmet technological need to develop database platforms that can evaluate key biological hypotheses by querying extensive single-cell datasets. Large single-cell datasets like Human Cell Atlas and COVID-19 cell atlas (collection of annotated sc datasets from various human organs) are excellent resources for profiling target genes involved in human diseases and disorders ranging from oncology, auto-immunity, as well as infectious diseases like COVID-19 caused by SARS-CoV-2 virus. SARS-CoV-2 infections have led to a worldwide pandemic with massive loss of lives, infections exceeding 7 million cases. The virus uses ACE2 and TMPRSS2 as key viral entry associated proteins expressed in human cells for infections. Evaluating the expression profile of key genes in large single-cell datasets can facilitate testing for diagnostics, therapeutics, and vaccine targets, as the world struggles to cope with the on-going spread of COVID-19 infections., Main Body: In this manuscript we describe REVEAL: SingleCell, which enables storage, retrieval, and rapid query of single-cell datasets inclusive of millions of cells. The array native database described here enables selecting and analyzing cells across multiple studies. Cells can be selected using individual metadata tags, more complex hierarchical ontology filtering, and gene expression threshold ranges, including co-expression of multiple genes. The tags on selected cells can be further evaluated for testing biological hypotheses. One such example includes identifying the most prevalent cell type annotation tag on returned cells. We used REVEAL: SingleCell to evaluate the expression of key SARS-CoV-2 entry associated genes, and queried the current database (2.2 Million cells, 32 projects) to obtain the results in < 60 s. We highlighted cells expressing COVID-19 associated genes are expressed on multiple tissue types, thus in part explains the multi-organ involvement in infected patients observed worldwide during the on-going COVID-19 pandemic., Conclusion: In this paper, we introduce the REVEAL: SingleCell database that addresses immediate needs for SARS-CoV-2 research and has the potential to be used more broadly for many precision medicine applications. We used the REVEAL: SingleCell database as a reference to ask questions relevant to drug development and precision medicine regarding cell type and co-expression for genes that encode proteins necessary for SARS-CoV-2 to enter and reproduce in cells.

Background: Inflammation has become the culmination point for several chronic diseases like skin diseases, asthma, neurological disorders, cancer, and cardiovascular disorders. Mini αA-crystallin peptide, identified from a highly conserved region of human lens protein αA-crystallin, is known to have a chaperone-like function; hence, it has generated interest in exploring the anti-inflammatory potential of the peptide., Objective: The objective of the study was to evaluate the anti-inflammatory potential of mini αA chaperones using in vitro, ex-vivo, and in vivo models., Methods: The peptide was tested for its phosphodiestarase4 B inhibition, anti-inflammatory and free radical scavenging abilities in HaCaT cells. Carbopol gel formulations with varying concentrations of mini αA-crystallin peptide and diclofenac sodium were prepared and optimized. Skin permeation studies of prepared formulations were carried out on excised abdominal skin of Wistar rat using a vertical type diffusion cell. Carrageenan induced rat paw oedema model was used for determining the anti-inflammatory potential of the peptide in prepared gel formulation with or without diclofenac sodium., Results: The peptide exhibited appreciable free radical scavenging and weak PDE4B inhibition. Gel formulation with 1% Tween-80, 1% carbopol, and 10% ethanol showed better permeation compared to other formulations. The in vitro skin permeation studies revealed good improvement in permeation characteristics of diclofenac and peptide from the gels. The peptide was retained within the skin tissue, which is an ideal requirement for the delivery of an anti-inflammatory topical formulation. In preclinical anti-inflammatory studies, gel formulation containing mini αA-peptide and diclofenac sodium showed a significant decrease in paw volume compared to other combinations tested., Conclusion: The study revealed the additive effect in anti-inflammatory activity by combining mini-αA peptide and diclofenac sodium which effectively reduced the inflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Identification of risk factors for perioperative complications helps in the prognostication. We wanted to determine whether Physiological and Operative Severity Score for the enumeration of mortality and morbidity (POSSUM) and Portsmouth-POSSUM (P-POSSUM) can be used in patients undergoing head and neck oncosurgery., Methods: We conducted a retrospective analysis of 1265 patients after they had major head and neck oncosurgeries. Demographic, surgical and outcome data was collected. We separately analyzed data for patients who had undergone cancer surgery for oral cavity, pharynx, and larynx. We calculated the POSSUM and P-POSSUM scores., Results: POSSUM scoring system had moderate discrimination (AUC = 0.61) and good calibration (P = .36) for the entire study cohort and in the subgroup. Since there were no deaths in the entire cohort, we were not able to check predictive ability of the scores, for mortality., Conclusions: We found that POSSUM had moderate discrimination and good calibration for morbidity prediction in head and neck cancer surgeries, as well as for the selected subgroup., (© 2020 Wiley Periodicals LLC.)

Synchronous malignancies arising from head and neck and thorax are rare presentation, and only few cases are reported in the scientific literature. We report three cases of double primary malignancies treated at our hospital., Competing Interests: None

The on-target pioneer factors Ascl1 and Myod1 are sequence-related but induce two developmentally unrelated lineages-that is, neuronal and muscle identities, respectively. It is unclear how these two basic helix-loop-helix (bHLH) factors mediate such fundamentally different outcomes. The chromatin binding of Ascl1 and Myod1 was surprisingly similar in fibroblasts, yet their transcriptional outputs were drastically different. We found that quantitative binding differences explained differential chromatin remodelling and gene activation. Although strong Ascl1 binding was exclusively associated with bHLH motifs, strong Myod1-binding sites were co-enriched with non-bHLH motifs, possibly explaining why Ascl1 is less context dependent. Finally, we observed that promiscuous binding of Myod1 to neuronal targets results in neuronal reprogramming when the muscle program is inhibited by Myt1l. Our findings suggest that chromatin access of on-target pioneer factors is primarily driven by the protein-DNA interaction, unlike ordinary context-dependent transcription factors, and that promiscuous transcription factor binding requires specific silencing mechanisms to ensure lineage fidelity.

Purpose: To our knowledge, we conducted the first prospective oncologic clinical trial in Nepal aimed at providing state-of-the-art chemotherapy to patients with Ewing sarcoma. The efficacy of external-beam radiotherapy (RT) as the sole local treatment modality was explored and deemed justified as a result of the lack of available advanced tumor-orthopedic services in Nepal., Patients and Methods: Twenty patients, 11 female and 9 male patients between the ages of 6 and 37 years, with newly diagnosed Ewing sarcoma were enrolled. Neoadjuvant combination chemotherapy, comprising well-established drug combinations, was administered in five courses before external-beam RT, during which one course of etoposide and ifosfamide was given. After RT, six additional chemotherapy courses were scheduled., Results: RT was tolerated well, providing rapid symptom relief and local tumor control, with no pathologic fractures observed among the 15 patients who received such treatment. Eleven patients completed the entire treatment protocol; seven patients were under continued follow-up, with no evidence of disease in six patients at a median follow-up time of 2.3 years (range, 1.3 to 3.1 years) and one patient alive but with a regional recurrence. Four patients experienced metastatic relapse and died as a result of their disease. Three treatment-related deaths linked to toxicity from chemotherapy occurred. Four of the six patients who refused to complete the treatment protocol and were lost to follow-up experienced progressive disease and were assumed dead., Conclusion: This study was feasible with RT as the sole local treatment modality in combination with chemotherapy. As a result of the high number of patients lost to follow-up, no firm conclusions can be drawn, but the majority of the patients who completed treatment obtained durable long-term remissions.

The problem of longer retention times using water-rich mobile phases in reversed phase liquid chromatography (RPLC) has been addressed using hydrophobic alcohols such as butanol in very low quantities (approximately 0.1%) as the organic modifier. Advantages of water-rich mobile phases in RPLC for the separation of water-soluble and weakly retained compounds are improved separation of congeners and better tuning of RPLC separations. This is demonstrated in the separation of gentisic acid and related renal cell carcinoma (RCC) biomarkers in urine with a Zorbax C 18 column and a mobile phase of 0.1% (volume/volume) butanol in water with 0.6% (volume/volume) acetic acid. Calibration curves for the RCC biomarkers were linear over the concentration range investigated (5 ppm to 1000 ppm). Detection limits for the RCC biomarkers were 0.85ppm (quinolinic acid), 1.75ppm (gentisic acid), and 1.25ppm (4-hydroxybenzoic acid). Recovery tests using synthetic urine samples containing 20 ppm, 100 ppm, and 700 pm of each RCC biomarker were successful for all compounds.

Objectives: To investigate the influence of micro-osteoperforation (MOP) on rate of orthodontic tooth movement and pain perception with fixed appliances., Design: 2 arm parallel randomized controlled trial with an allocation ratio of 1:1., Setting: The outpatient department of a dental college., Participants: 105 patients were screened, out of which 60 met the inclusion criteria and consented to participate; consisting of 33 females and 27 males requiring en-masse retraction following first premolar extractions., Methods: The experimental group consisted of patients bonded with a fixed appliance (Gemini 3M) who received MOP distal to canines throughout the period of retraction every 28 days. These were compared with a control group treated with identical brackets without MOP and were assessed for rate of tooth movement (canine retraction) and pain perception using a Visual Analogue Scale (VAS) of 10 mm., Results: Prior to commencement, all baseline parameters were matched between the two groups (p>0.05). A statistically significant increase in rate of tooth movement in the MOP group (p<0.05)., Conclusion: MOP appears to enhance the rate of tooth movement with no differences in pain perception.

Monodispersed Fe 3 O 4 magnetic nanoparticles (MNPs) having size of 7 nm have been prepared from iron oleate and made water dispersible by functionalization for biomedical applications. Three different reactions employing thioglycolic acid, aspartic acid and aminophosphonate were performed on oleic acid coated Fe 3 O 4 . In order to achieve a control on particle size, the pristine nanoparticles were heated in presence of ferric oleate which led to increase in size from 7 to 11 nm. Reaction parameters such as rate of heating, reaction temperature and duration of heating have been studied. Shape of particles was found to change from spherical to cuboid. The cuboid shape in turn enhances magneto-crystalline anisotropy (K u ). Heating efficacy of these nanoparticles for hyperthermia was also evaluated for different shapes and sizes. We demonstrate heat generation from these MNPs for hyperthermia application under alternating current (AC) magnetic field and optimized heating efficiency by controlling morphology of particles. We have also studied intra-cellular uptake and localization of nanoparticles and cytotoxicity under AC magnetic field in human breast carcinoma cell line.

Background and Aims: Patients undergoing ovarian cancer surgery after chemotherapy and requiring opioid-based patient-controlled analgesia (PCA) are at high-risk of postoperative nausea and vomiting (PONV). We aimed to assess the effect of palonosetron and dexamethasone combination for these patients for prevention of PONV., Methods: This study included 2 groups and 150 patients. At the time of wound closure, patients in group A received ondansetron 8 mg intravenous (IV) + dexamethasone 4 mg IV and group B received palonosetron 0.075 mg IV + dexamethasone 4 mg IV. Postoperatively for 48 hours, group A patients received ondansetron 4 mg 8 hourly IV, group B patients received normal saline 8 hourly IV in 2 cc syringe. The primary objective was the overall incidence of PONV. Independent t -test, Chi-square test, and Fisher's exact test were used and multivariate regression analysis was done., Results: Vomiting was significantly higher in group A (37.3%) as compared with group B (21.3%) at 0-48 hours ( P = 0.031). Significantly more patients in Group A had nausea as compared with group B at 90-120 minutes (30.66% vs 18.66%, P = 0.043) and 6-24 hours (32.0% vs 22.66%, P = 0.029). PCA opioid usage in microgram was significantly higher in group A at 0-24 hours (690.53 ± 332.57 vs 576.85 ± 250.79, P = 0.024) and 0-48 hours (1126.10 ± 512.18 vs 952.13 ± 353.85, P = 0.030)., Conclusion: Palonosetron with dexamethasone is more effective than ondasetron with dexamethasone for prevention of PONV in post-chemotherapy ovarian cancer surgeries receiving opioid-based patient controlled analgesia., Competing Interests: There are no conflicts of interest.

The Canadian Penning Trap mass spectrometer at the Californium Rare Isotope Breeder Upgrade (CARIBU) facility was used to measure the masses of eight neutron-rich isotopes of Nd and Sm. These measurements are the first to push into the region of nuclear masses relevant to the formation of the rare-earth abundance peak at A∼165 by the rapid neutron-capture process. We compare our results with theoretical predictions obtained from "reverse engineering" the mass surface that best reproduces the observed solar abundances in this region through a Markov chain Monte Carlo technique. Our measured masses are consistent with the reverse-engineering predictions for a neutron star merger wind scenario.

The structure of deformed neutron-rich nuclei in the rare-earth region is of significant interest for both the astrophysics and nuclear structure fields. At present, a complete explanation for the observed peak in the elemental abundances at A∼160 eludes astrophysicists, and models depend on accurate quantities, such as masses, lifetimes, and branching ratios of deformed neutron-rich nuclei in this region. Unusual nuclear structure effects are also observed, such as the unexpectedly low energies of the first 2^{+} levels in some even-even nuclei at N=98. In order to address these issues, mass and β-decay spectroscopy measurements of the ^{160}Eu&#95;{97} and ^{162}Eu&#95;{99} nuclei were performed at the Californium Rare Isotope Breeder Upgrade radioactive beam facility at Argonne National Laboratory. Evidence for a gap in the single-particle neutron energies at N=98 and for large deformation (β&#95;{2}∼0.3) is discussed in relation to the unusual phenomena observed at this neutron number.

A reversed phase liquid chromatographic (RPLC) method was developed to simultaneously detect and quantify creatinine, quinolinic acid, gentisic acid and 4-hydroxybenzoic acid in urine. These four bio-markers are present in relatively high concentrations in urine. Using a 5% methanol in water mobile phase with 0.6% acetic acid and a Zorbax C 18 column, baseline resolution for all four biomarkers in synthetic urine was achieved. Better resolution was obtained for the separation of these four compounds when water rich mobile phases were used. Detection of the four biomarkers in urine using the proposed RPLC method is limited by background from the urine matrix for the later eluting compounds and from the dead marker for earlier eluting compounds.

Continued evolution of highly pathogenic H5N1 viruses causing high mortality in humans obviates need for broadly cross-reactive vaccines. For this, hemagglutinin (HA) inducing specific protective antibodies, highly conserved nucleoprotein (NP), and ectodomain of matrix (M2e) protein, either singly or in combination, were evaluated in BALB/c mice. Recombinant HA and NP (baculovirus system) and M2e (synthetic peptide) and 3 adjuvants, that is, liposomes, Mw (heat killed Mycobacterium w), and alum were utilized for the homologous virus challenge. Additional immunogens included liposome-encapsulated HA/NP proteins and corresponding DNAs. Mice groups received two doses of respective formulations given at 3-week intervals and challenged intranasally with 100LD50 of H5N1 virus strain. Dynamics of weight loss, lung viral load, titres of IgG-anti-HA, NP, and M2e antibodies (ELISA), and IgG-subtype analysis was done. Two doses of all the formulations led to 100% seroconversion against the immunogens evaluated (100% seroconversion after the first dose in majority). Antibody titres against the components were dependent on the adjuvant and combination. HA-driven Th2 response with all the adjuvants, balanced Th1/Th2 response to NP protein, and Th2-bias with alum were noted. Low anti-M2e antibody titres did not allow subtype analysis. On challenge, complete protection was observed with Mw-HA, alum-HA+NP, Lipo-HA+NP+M2e, alum-HA+NP+M2e, and HA-DP formulations with 12-fold, 8-fold, 720-fold, 17-fold, and no reduction, respectively, in lung viral load. In conclusion, the results identify several adjuvant-immunogen combinations conferring 100% protection in mice that need further evaluation in higher animals.

Introduction: The incidence of melanoma has increased over the last decade. The Breslow thickness is one of the most important histological parameters. The gold standard for histological diagnosis is an excision biopsy. Incisional, punch or shave biopsies are not recommended as they are often incomplete and can result in false negatives., Objective: To assess the validity of incision versus excision biopsies in the prediction of Breslow thickness in the histopathological analysis of malignant melanoma., Methods: A retrospective review of histopathological records was conducted for all patients undergoing incision biopsy for malignant melanoma. The Breslow thicknesses of the incisional biopsies were matched to the later corresponding excisional biopsies. The demographical data, site of melanoma and histological subtype were also examined., Results: Sixty patients between 1st January 2005 and 31st December 2013 were identified. The most common area biopsied was the upper and lower limbs - 50%. The Breslow thickness and Clark's level were found to be significantly increased in excision versus incision biopsy specimens. Nine patients had differing mitotic rates which were all higher in the excision biopsy samples., Conclusion: Our data supports the UK national guidelines on the management of malignant melanoma in that incisional biopsies are not indicated in the diagnostic pathway of malignant melanoma.

In the standard model, the weak interaction is formulated with a purely vector-axial-vector (V-A) structure. Without restriction on the chirality of the neutrino, the most general limits on tensor currents from nuclear β decay are dominated by a single measurement of the β-ν[over ¯] correlation in ^{6}He β decay dating back over a half century. In the present work, the β-ν[over ¯]-α correlation in the β decay of ^{8}Li and subsequent α-particle breakup of the ^{8}Be^{*} daughter was measured. The results are consistent with a purely V-A interaction and in the case of couplings to right-handed neutrinos (C&#95;{T}=-C&#95;{T}^{'}) limits the tensor fraction to |C&#95;{T}/C&#95;{A}|^{2}<0.011 (95.5% C.L.). The measurement confirms the ^{6}He result using a different nuclear system and employing modern ion-trapping techniques subject to different systematic uncertainties.

This investigation reports the preparation of agglomerated Fe 3 O 4 nanoparticles and evaluation of its utility as a viable carrier in the preparation of radiolanthanides as potential therapeutic agents for the treatment of arthritis. The material was synthesized by a chemical route and characterized by XRD, FT-IR, SEM, EDX and TEM analysis. The surface of agglomerated particle possessed ion pairs (-O - :Na + ) after dispersing particles in a NaHCO 3 solution at pH = 7 which is conducive for radiolanthanide (*Ln = 90 Y, 153 Sm, 166 Ho, 169 Er, 177 Lu) loading by replacement of Na + ions with tripositive radiolanthanide ions. Radiolanthanide-loaded particulates exhibited excellent in vitro stability up to ∼3 half-lives of the respective lanthanide radionuclides when stored in normal saline at 37 °C. The radiochemical purities of the loaded particulates were found to be retained to the extent of >70% after 48 h of storage when challenged by a strong chelator DTPA present at a concentration as high as 5 mM, indicating fairly strong chemical association of lanthanides with agglomerated Fe 3 O 4 nanoparticles. Biodistribution studies of 90 Y and 166 Ho-loaded particulates carried out after intra-articular injection into one of the knee joints of a normal Wistar rat revealed near-complete retention of the radioactive preparations (>98% of the administered radioactivity) within the joint cavity even after 72 h post injection. This was further confirmed by sequential whole-body radio-luminescence imaging. These experimental results are indicative of the potential use of radiolanthanide-loaded agglomerated Fe 3 O 4 nanoparticles for the treatment of arthritis.

The gyraseB subunit of Staphylococcus aureus DNA gyrase is a well-established and validated target though less explored for the development of novel antimicrobial agents. Starting from the available structural information in PDB (3TTZ), we identified a novel series of benzimidazole used as inhibitors of DNA gyraseB with low micromolar inhibitory activity by employing structure-based drug design strategy. Subsequently, this chemical class of DNA gyrase inhibitors was extensively investigated biologically through in vitro assays, biofilm inhibition assays, cytotoxicity, and in vivo studies. The binding affinity of the most potent inhibitor 10 was further ascertained biophysically through differential scanning fluorimetry. Further, the most potent analogues did not show any signs of cardiotoxicity in Zebra fish ether-a-go-go-related gene (zERG), a major breakthrough among the previously reported cardiotoxic gyraseB inhibitors., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: The incidence of postoperative pharyngolaryngeal complications after laryngeal mask airway (LMA) insertion can be as high as 50%. Over-inflation of the LMA cuff may be a causal factor. We conducted a single-centre parallel group randomised trial to determine whether maintaining LMA-ProSeal intra-cuff pressures below 60 cm H2O decreases postoperative pharyngolaryngeal complications., Methods: We recruited 120 adult patients who were scheduled to undergo elective surgery under general anaesthesia. Appropriate sized LMA-ProSeal was inserted and the cuff was inflated with air (to no more than the maximum recommended volume) until there was no audible leak. Patients were randomised to either the control group (n = 60), where the intra-cuff pressure was noted and no further action was taken, or to the pressure-monitored group (n = 60), where intra-cuff pressure was maintained below 60 cm H2O. Pharyngolaryngeal complications consisting of sore throat, dysphonia and dysphagia were assessed at 1, 2, and 24 h postoperatively. Patients, anaesthesiologists and assessors were blinded to group allocation. The primary outcome was a composite endpoint of any pharyngolaryngeal complication at any of the three time points. Secondary outcomes were the incidence of individual outcomes at each time point., Results: The incidence of pharyngolaryngeal complications at any time point was 42% in the routine care group and 32% in the pressure-monitored group (95% CI for difference +28 to -7%, p = 0.26). There was no difference between groups for any of the secondary outcomes., Conclusion: Our study failed to demonstrate a statistically significant reduction in postoperative pharyngolaryngeal complications by limiting intra-cuff pressures in the LMA-Proseal.

Background: Recently, we have reported antihypertensive activity of oleanolic acid (OA) in glucocorticoid-induced hypertension with restoration of nitric oxide (NO) level. However, the involvement of NO-releasing action of OA was unclear., Objective: To explore antihypertensive activity of OA in N(ω)-nitro-L-arginine methyl ester (L-NAME) hypertensive rats wherein NO is completely blocked, which would allow exploring the possibility of involvement of NO-releasing action of OA., Materials and Methods: Five groups of rats were investigated as normal control, L-NAME (40 mg/kg/day), L-NAME + enalapril (15 mg/kg/day), L-NAME + l-arginine (100 mg/kg/day), and L-NAME + OA (60 mg/kg/day) for 4 weeks. The systolic blood pressure, body weight, and heart rate were measured weekly for 4 weeks. Serum nitrate/nitrite (NOx) level, urine electrolytes concentration, cardiac mass index, and serum creatinine level were determined followed by organ histopathology., Results: OA and enalapril delayed the rise in blood pleasure following L-NAME administration. Decreased serum NOx level was not significantly increased with any of the treatment. OA produced a small, though nonsignificant, increase in the NOx level. L-NAME administration did not affect cardiac mass index. There was an increase in serum creatinine upon L-NAME administration which was prevented by OA. Decreased urine volume, urine sodium and potassium were reversed by OA., Conclusion: These results suggest that the antihypertensive effect of OA in L-NAME hypertension is due to diuresis and nephroprotection. However, OA has nonsignificantly affected the NO levels.

Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600,000-700,000 deaths in India were caused by cancer in 2012. In age-standardised terms this figure is close to the mortality burden seen in high-income countries. Such figures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of India's cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affluent. In this first of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India., (Copyright © 2014 Elsevier Ltd. All rights reserved.)