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Byline: G. Gopan, Lakshmi. Kumar, Anjana. Babu, Abish. Sudhakar, Rubin. George, Vidya. Menon Background and Aims: Myocardial injury after non-cardiac surgery (MINS) is associated with high postoperative mortality. We sought [...]

The indications for mitral valve repair extend across the entire spectrum of degenerative mitral valve disease, ranging from fibroelastic degeneration to Barlow's disease. Collaboration between the surgeon and anesthesiologist is essential for ensuring optimal results. Echocardiographic assessment of the repair can be challenging but is essential to the success of the procedure, as even mild residual mitral regurgitation can portend poor patient outcomes. In addition to determining the severity of residual regurgitation, the anesthesiologist must elucidate the mechanism of disease in order to inform appropriate re-intervention measures. Finally, there are unique complications of mitral valve surgery for the anesthesiologist to understand and assess by echocardiography. This review describes a systematic pathway for a comprehensive intraoperative assessment of the mitral valve following surgical repair. [ABSTRACT FROM AUTHOR]

Applications of unmanned aerial vehicles (UAVs) have proliferated in the last decade due to the technological advancements on various fronts such as structure-from-motion (SfM), machine learning, and robotics. An important preliminary step with regard to forest inventory and management is individual tree detection (ITD), which is required to calculate forest attributes such as stem volume, forest uniformity, and biomass estimation. However, users may find adopting the UAVs and algorithms for their specific projects challenging due to the plethora of information available. Herein, we provide a step-by-step tutorial for performing ITD using (i) low-cost UAV-derived imagery and (ii) UAV-based high-density lidar (light detection and ranging). Functions from open-source R packages were implemented to develop a canopy height model (CHM) and perform ITD utilizing the local maxima (LM) algorithm. ITD accuracy assessment statistics and validation were derived through manual visual interpretation from high-resolution imagery and field-data-based accuracy assessment. As the intended audience are beginners in remote sensing, we have adopted a very simple methodology and chosen study plots that have relatively open canopies to demonstrate our proposed approach; the respective R codes and sample plot data are available as supplementary materials.

The ET tube cuff high up in the larynx compresses the RLN branches against the thyroid cartilage and stretches the hypoglossal nerve against the hyoid bone.[[1]] The high-cuff pressure also increases the risk for nerve injury. To the editor, Tapia's syndrome is a rare complication with injury to the hypoglossal (XIIth) and vagus (Xth) nerves resulting in a weak voice, increased predilection for aspiration, and difficulty in swallowing. Antonio Garcias Tapia first named this syndrome in a bullfighter with Xth and XIIth nerve palsy after sustaining carotid artery injury resulting in compromised neural blood supply. [Extracted from the article]

Chronic Suppurative Otitis Media (CSOM) is an inflammation of the mucoperiosteal lining of the middle ear cleft. Recently, biofilms have been discovered to play a pivotal role in the pathogenesis of CSOM. A biofilm is a bacterial aggregation that adheres to the mucosal surfaces and is connected with an extracellular matrix. Biofilms enhance antibiotic resistance, facilitate genetic alterations and amplify competence to combat host immunity. This study aims to identify the spectrum of biofilm-producers in CSOM and investigate their antibiotic sensitivity. Samples (648) were obtained from the deeper part of external auditory meatus of patients with CSOM. Pus samples were collected and processed for culture sensitivity. Biofilms detected. The findings were compiled and statistically analyzed. Out of 500 culture-positive samples, most commonly isolated bacteria was Pseudomonas (62.6%), followed by MRSA (13.8%). Biofilm-producers were 350, with 119 being strong, 167 moderate, and 64 weak. Biofilms were produced by 70% of the isolates, with Pseudomonas producing the most (74.6%), followed by MRSA. Gentamicin was the most effective antibiotic against biofilm-producers. Amoxicillin-Clavulanic Acid, Ceftriaxone, Cefuroxime, and Minocyclin were resistant. Pseudomonas had the highest sensitivity to Levofloxacin (96.6%), followed by Ceftazidime and Ciprofloxacin. Pseudomonas was resistant to Cefuroxime, Amoxicillin-Clavulanic acid and Linezolid. Multi-drug resistance has been widespread among CSOM causal species, particularly in biofilm producers. Thus, screening for biofilm formation, in addition to the standard antibiogram, must be undertaken as part of CSOM protocol. This will address the multi-drug resistance and select an appropriate treatment modality., (© Association of Otolaryngologists of India 2024. 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.)

Malaria is an intracellular protozoan parasitic disease caused by Plasmodium species with significant morbidity and mortality in endemic regions. The complex lifecycle of the parasite and the emergence of drug-resistant Plasmodium falciparum have hampered the efficacy of current anti-malarial agents. To circumvent this situation, the present study attempts to demonstrate the blood-stage anti-plasmodial action of 26 hybrid compounds containing the three privileged bioactive scaffolds (sulfonamide, chalcone, and nitro group) with synergistic and multitarget action. These three parent scaffolds exhibit divergent activities, such as antibacterial, anti-malarial, anti-fungal, anti-inflammatory, and anticancer. All the synthesised compounds were characterised using various spectroscopic techniques. The in vitro blood-stage inhibitory activity of 26 hybrid compounds was evaluated against mixed-stage culture (asynchronize) of human malarial parasite P. falciparum, Pf 3D7 at different concentrations ranging from 25.0 µg/mL to 0.78 µg/mL using SYBR 1 green assay, with IC 50 values determined after 48 h of treatment based on the drug-response curves. Two potent compounds (11 and 10), with 2-Br and 2,6-diCl substitutions, showed pronounced activity with IC 50 values of 5.4 µg/mL and 5.6 µg/mL, whereas others displayed varied activity with IC 50 values ranging from 7.0 µg/mL to 22.0 µg/mL. Both 11 and 10 showed greater susceptibility towards mature-stage trophozoites than ring-stage parasites. The hemolytic and in vitro cytotoxicity assays revealed that compounds 11 and 10 did not cause any toxic effects on host red blood cells (uninfected), human-derived Mo7e cells, and murine-derived BA/F3 cells. The in vitro observations are consistent with the in silico studies using P. falciparum-dihydrofolate reductase, where 11 and 10 showed a binding affinity of -10.4 Kcal/mol. This is the first report of the hybrid scaffold, 4-nitrobenzenesulfonamide chalcones, demonstrating its potential as an anti-plasmodial agent., (© 2024 Wiley Periodicals LLC.)

Keloids are fibroproliferative disorders caused due to injury to skin. The recurrence rate has been found to be as high as 100% even after surgical excision. The high recurrence rate has led to the need for various adjuvant therapies as a single approach alone has not been found to be efficient in preventing recurrence. This attributes to the need for a multimodal approach. Steroids are found to be useful in preventing recurrence. To evaluate the efficacy of the combination of hyaluronidase with corticosteroid injection compared to corticosteroid injection alone in the prevention of recurrence of keloid after surgical excision. This randomized controlled study was conducted in the Department of Otorhinolaryngology among 50 patients with ear keloids who underwent surgical excision. Patients were divided into two groups. One group was given Triamcinolone injection alone and the other was given Triamcinolone with Hyaluronidase on postoperative weeks 1, 2, and 3. Patients were followed up for 6 months and recurrence was noted and compared. Statistical analysis was done and the results were considered significant with a p-value of less than 0.05. Of the total 50 patients, there were a total of eight male and 39 female patients. In a single therapy group, recurrence was noted in one patient after 3 months and in three more patients after 6 months. In the group with combination therapy, there was no recurrence after 3 months but three patients had recurrence after 6 months. Triamcinolone and hyaluronidase injection protected from recurrence for about 3 to 5 months after which patients had recurrence. Further studies are recommended with prolonged duration of hyaluronidase injection., Competing Interests: Competing InterestsThe authors declare that they have no competing interests., (© Association of Otolaryngologists of India 2024. 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.)

The development of synthetic hydrogels as a dermal patch offers unique advantage of providing moist environment around the wound site. The incorporation of curcumin in hydrogel plays a significant role in the healing process of chronic wounds. The present investigation aims to develop nano-formulated curcumin-fused lipogel to impart the dual advantages of sustained drug release and enhanced wound healing ability. The wound healing behaviour of the prepared lipogel has been assessed through series of techniques namely DPPH assay and bacterial inhibitory efficacy through the Kirby Bauer assay against E. coli and S. aureus. Further, the promotion of angiogenesis has been determined through an in-ovo CAM assay. The results obtained from the investigation revealed the enhanced solubility of curcumin in liposome formulation. Moreover, the encapsulation of curcumin in liposomes facilitated prolonged drug release and better antibacterial efficacy against the tested bacterial stains. The developed hydrogel also displayed good adhesion and water retention ability, which is an important prerequisite for better wound healing ability., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD), affecting millions of people worldwide and expected to impact 10 million by 2030, manifests a spectrum of motor and non-motor symptoms linked to the decline of dopaminergic neurons. Current therapies manage PD symptoms but lack efficacy in slowing disease progression, emphasizing the urgency for more effective treatments. Resveratrol (RSV), recognized for its neuroprotective and antioxidative properties, encounters challenges in clinical use for PD due to limited bioavailability. Researchers have investigated lipid-based nanoformulations, specifically solid lipid nanoparticles (SLNs), to enhance RSV stability. Oral drug delivery via SLNs faces obstacles, prompting exploration into transdermal delivery using SLNs integrated with microneedles (MNs) for improved patient compliance. In this study, an RSV-loaded SLNs (RSV -SLNs) incorporated into the MN patch was developed for transdermal RSV delivery to improve its stability and patient compliance. Characterization studies demonstrated favorable physical properties of SLNs with a sustained drug release profile of 78.36 ± 0.74%. The developed MNs exhibited mechanical robustness and skin penetration capabilities. Ex vivo permeation studies displayed substantial drug permeation of 68.39 ± 1.4% through the skin. In an in vivo pharmacokinetic study, the RSV-SLNs delivered through MNs exhibited a significant increase in C max , T max , and AUC 0 - t values, alongside a reduced elimination rate in blood plasma in contrast to the administration of pure RSV via MNs. Moreover, an in vivo study showcased enhanced behavioral functioning and increased brain antioxidant levels in the treated animals. In-vivo skin irritation study revealed no signs of irritation till 24 h which permits long-term MNs application. Histopathological analysis showed notable changes in the brain regions of the rat, specifically the striatum and substantia nigra, after the completion of the treatment. Based on these findings, the development of an RSV-SLN loaded MNs (RSVSNLMP) patch presents a novel approach, with the potential to enhance the drug's efficiency, patient compliance, and therapeutic outcomes for PD, offering a promising avenue for advanced PD therapy., (© 2024. Controlled Release Society.)

The clinical use of selegiline hydrochloride in conventional dosage forms is to reduce the progression of Parkinson's disease (PD). However, its limited access to the brain, short half-life, and first-pass metabolism minimize brain uptake. Nano-based liposomes offer promising tools for brain-targeted delivery of therapeutics, especially intranasally administered cationic liposomes that target the brain region via the olfactory route and reduce biodistribution. In the present work, cationic liposomes encapsulated with selegiline hydrochloride were fabricated for intranasal administration against PD. The liposomes were initially optimized by Box Behnken design, and the selected run was coated with stearylamine to provide a cationic charge to the liposomes. The final coated liposomes, SH-LP3, demonstrated a minimum size of 173 ± 2.13 nm, an ideal zeta potential of +16 ± 1.98, and achieved a maximum entrapment efficiency of 40.14 ± 1.83%. Morphology analysis showed the spherical shape of liposomes in the size range of 100-200 nm. The in vitro cytotoxicity assay in SHSY5Y cell lines showed a significant decrease in toxicity, almost ten times less, compared to pure selegiline hydrochloride. Animal studies on rotenone-lesioned C57BL6 mice model for PD were performed to investigate the effect of intranasally administered liposomes. The SH-LP3 formulation exhibited remarkable effectiveness in relieving symptoms of PD. This extensive analysis emphasizes the possibility of intranasally administered SH-LP3 liposomes as a feasible treatment option for PD. The formulation not only delivers continuous drug release but also displays better safety and efficacy, providing a platform for additional studies and growth in the domain of PD treatment.

Neurodegenerative disease (ND) is the fourth leading cause of death worldwide, with limited symptomatic therapies. Mitochondrial dysfunction is a major risk factor in the progression of ND, and it-increases the generation of reactive oxygen species (ROS). Overexposure to these ROS induces apoptotic changes leading to neuronal cell death. Many studies have shown the prominent effect of phytobioactive compounds in managing mitochondrial dysfunctions associated with ND, mainly due to their antioxidant properties. The drug delivery to the brain is limited due to the presence of the blood-brain barrier (BBB), but effective drug concentration needs to reach the brain for the therapeutic action. Therefore, developing safe and effective strategies to enhance drug entry in the brain is required to establish ND's treatment. The microneedle-based drug delivery system is one of the effective non-invasive techniques for drug delivery through the transdermal route. Microneedles are micronsized drug delivery needles that are self-administrable. It can penetrate through the stratum corneum skin layer without hitting pain receptors, allowing the phytobioactive compounds to be released directly into systemic circulation in a controlled manner. With all of the principles mentioned above, this review discusses microneedles as a versatile drug delivery carrier for the phytoactive compounds as a therapeutic potentiating agent for targeting mitochondrial dysfunction for the management of ND., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tissue engineering has gained prominence during the past decade since it offers a key solution to defects associated with the tissue regeneration. The limited healing potential of the cartilage tissue damage has significant clinical implications. Herein, dysprosium (Dy 3+ ) impregnated polyvinyl alcohol (PVA) hydrogels have been developed to enhance the therapeutic efficacy, enabling simultaneous diagnostic imaging and antibacterial drug delivery for potential applications in articular cartilage. Based on the favorable imaging features, Dy 3+ impregnated PVA hydrogels with enhanced stability were formed through successive steps of repeated cycles of freezing at - 30 °C for 21 h, thawing at 25 °C for 4 h and lyophilization. The tensile and compression tests of the hydrogels respectively determined a maximum of 3.88 and 1.58 MPa, which reflected better compatibility towards cartilage. The hydrogels fetched a sustained drug release for a period of 12 h with an associated swelling ratio of 80%. The potential of the resultant hydrogels in image diagnosis has been deliberated through their blue and yellow emissions in the visible region. Further, the computed tomography (CT) and magnetic resonance imaging characteristics of the hydrogels respectively accomplished a maximum of 343 Hounsfiled units (HU) and relaxivity of 7.25 mM -1 s -1 . The cytocompatibility of the hydrogels is also determined through in vitro tests performed in Murine pro B cell line (BA/F3) and human Megakaryocyte cell line (Mo7e) cell lines., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and no significant financial support has been put forward to perform this work that could influence its outcome. We also confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obesity is a clinical condition with rising popularity and detrimental impacts on human health. According to the World Health Organization, obesity is the sixth most common cause of death worldwide. It is challenging to combat obesity because medications that are successful in the clinical investigation have harmful side effects when administered orally. The conventional approaches for treating obesity primarily entail synthetic compounds and surgical techniques but possess severe adverse effects and recurrences. As a result, a safe and effective strategy to combat obesity must be initiated. Recent studies have shown that biological macromolecules of the carbohydrate class, such as cellulose, hyaluronic acid, and chitosan, can enhance the release and efficacy of medications for obesity but due to their short biological half-lives and poor oral bioavailability, their distribution rate is affected. This helps to comprehend the need for an effective therapeutic approach via a transdermal drug delivery system. This review focuses on the transdermal administration, utilizing cellulose, chitosan, and hyaluronic acid via microneedles, as it offers a promising solution to overcome existing therapy limitations in managing obesity and it also highlights how microneedles can effectively deliver therapeutic substances through the skin's outer layer, bypassing pain receptors and specifically targeting adipose tissue., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Neurodegenerative diseases are the most widely affected disease condition in an aging population. The treatment available reduces the elevated manifestations but is ineffective due to the drug's poor bioavailability, plasma stability, and permeability across the blood-brain barrier (BBB). Until now, no therapeutic compound has been able to stop the progression of neurodegenerative disease. Even the available therapeutic moiety manages it with possible adverse effects up to the later stage. Hence, phytobioactive compounds of plant origin offer effective treatment strategies against neurodegenerative diseases. The only difficulty of these phytobioactive compounds is permeability across the BBB. Engineered nanocarriers such as liposomes provide high lipid permeability across BBB. Liposomes have unique physicochemical properties that are widely investigated for their application in diagnosing and treating neurodegenerative diseases. The surface modification on liposomes by peptides, antibodies, and RNA aptamers offers receptor targeting. These brain-targeted approaches by liposomes improve the efficacy of phytoconstituents. Additional surface modification methods are utilized on liposomes, which increases the brain-targeted delivery of phytobioactive compounds. The marketing strategy of the liposomal delivery system is in its peak mode, where it has the potential to modify the existing therapy. This review will summarize the brain target liposomal delivery of phytobioactive compounds as a novel disease-modifying agent for treating neurodegenerative diseases., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Neuraminidase (NA) of human influenza H3N2 virus has evolved rapidly and been accumulating mutations for more than half-century. However, biophysical constraints that govern the evolutionary trajectories of NA remain largely elusive. Here, we show that among 70 natural mutations that are present in the NA of a recent human H3N2 strain, >10% are deleterious for an ancestral strain. By mapping the permissive mutations using combinatorial mutagenesis and next-generation sequencing, an extensive epistatic network is revealed. Biophysical and structural analyses further demonstrate that certain epistatic interactions can be explained by non-additive stability effect, which in turn modulates membrane trafficking and enzymatic activity of NA. Additionally, our results suggest that other biophysical mechanisms also contribute to epistasis in NA evolution. Overall, these findings not only provide mechanistic insights into the evolution of human influenza NA and elucidate its sequence-structure-function relationship, but also have important implications for the development of next-generation influenza vaccines., (© 2022. The Author(s).)

Numerous naturally available phytochemicals have potential anti-cancer activities due to their vast structural diversity. Alkaloids have been extensively used in cancer treatment, especially lung cancers, among the plant-based compounds. However, their utilization is limited by their poor solubility, low bioavailability, and inadequacies such as lack of specificity to cancer cells and indiscriminate distribution in the tissues. Incorporating the alkaloids into nanoformulations can overcome the said limitations paving the way for effective delivery of the alkaloids to the site of action in sufficient concentrations, which is crucial in tumor targeting. Our review attempts to assess whether alkaloid nanoformulation can be an effective tool in lung cancer therapy. The mechanism of action of each alkaloid having potential is explored in great detail in the review. In general, Alkaloids suppress oncogenesis by modulating several signaling pathways involved in multiplication, cell cycle, and metastasis, making them significant component of many clinical anti-cancerous agents. The review also explores the future prospects of alkaloid nanoformulation in lung cancer. So, in conclusion, alkaloid based nanoformulation will emerge as a potential gamechanger in treating lung cancer in the near future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 S. M., Naveen, Rao, Gopan, Chopra, Park, Alshahrani, Jose, Emran and Kim.)

The RNA recognition motif (RRM) occurs widely in RNA-binding proteins, but does not always by itself support full binding. For example, it is known that binding of SL1 RNA to the protein U1-70K in the U1 spliceosomal particle is reduced when a region flanking the RRM is truncated. How the RRM flanking regions that together with the RRM make up an 'extended RRM' (eRRM) contribute to complex stability and structural organization is unknown. We study the U1-70K eRRM bound to SL1 RNA by thermal dissociation and laser temperature jump kinetics; long-time molecular dynamics simulations interpret the experiments with atomistic resolution. Truncation of the helix flanking the RRM on its N-terminal side, 'N-helix,' strongly reduces overall binding, which is further weakened under higher salt and temperature conditions. Truncating the disordered region flanking the RRM on the C-terminal side, 'C-IDR', affects the local binding site. Surprisingly, all-atom simulations show that protein truncation enhances base stacking interactions in the binding site and leaves the overall number of hydrogen bonds intact. Instead, the flanking regions of the eRRM act in a distributed fashion via collective interactions with the RNA when external stresses such as temperature or high salt mimicking osmotic imbalance are applied., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The demand for drug delivery systems (DDS) to treat Parkinson's disease (PD) is still high, and microneedle (MN) assisted transdermal DDS offers enormous potential. Herbal products for PD have been shown to have antioxidant effects in reducing dopaminergic neurons from degeneration. Here, we attempted to incorporate solid lipid nanoparticles (SLNs) of Bacopa monnieri into dissolvable microneedle arrays and evaluate its neuroprotective activity. The bloodless and painless microneedle arrays through the transdermal route deliver the drug across the blood-brain barrier at the desired concentration. The quality by design (QbD) approach was employed for optimizing the SLNs formulations. The mechanical strength, in vitro release studies, ex-vivo permeation investigation, skin irritation test, histopathological studies, biochemical studies, and behavioural tests SLNs loaded microneedle arrays were performed. The microneedle patches obtained were shown to be mechanically robust and were also found to be nonirritant with a decreased degree of bradykinesia, high motor coordination, and balance ability. Compared to systemic delivery systems, such an MN method can achieve a considerably lower effective dose and allow long-term home-based treatment., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Delna Joy et al.)

There are more than two hundred fifty different types of cancers, that are diagnosed around the world. Prostate cancer is one of the suspicious type of cancer spreading very fast around the world, it is reported that in 2018, 29430 patients died of prostate cancer in the United State of America (USA), and hence it is expected that one out of nine men diagnosed with this severe disease during their lives. Medical science has identified cancer at several stages and indicated genes mutations involved in the cancer cell progressions. Genetic implications have been studied extensively in cancer cell growth. So most efficacious drug for prostate cancer is highly required just like other severe diseases for men. So nutraceutical companies are playing major role to manage cancer disease by the recommendation of best natural products around the world, most of these natural products are isolated from plant and mushrooms because they contain several chemoprotective agents, which could reduce the chances of development of cancer and protect the cells for further progression. Some nutraceutical supplements might activate the cytotoxic chemotherapeutic effects by the mechanism of cell cycle arrest, cell differentiation procedures and changes in the redox states, but in other, it also elevate the levels of effectiveness of chemotherapeutic mechanism and in results, cancer cell becomes less reactive to chemotherapy. In this review, we have highlighted the prostate cancer and importance of nutraceuticals for the control and management of prostate cancer, and the significance of nutraceuticals to cancer patients during chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chopra, Bibi, Goyal, Gautam, Trivedi, Upadhyay, Mujahid, Shah, Haris, Khot, Gopan, Singh, Kim, Jose, Abdel-Daim, Alhumaydhi, Emran and Kim.)

The solubility transition at the lower critical solution temperature (LCST, 32 °C) of poly( N -isopropylacrylamide) (PNIPAM) is widely used as a thermal switch to rapidly and reversibly capture and release proteins and cells. It is generally assumed that proteins adsorbed to PNIPAM above the LCST are unaffected by polymer interactions. Here we show that the folding stability of the enzyme phosphoglycerate kinase (PGK) is increased by interactions with end-grafted PNIPAM films above the LCST. We systematically compare two protein mutants with different stabilities. The stabilization mirrors the degree of protein adsorption under grafting conditions studied previously. Maximum stabilization occurs when proteins adsorb to low density, collapsed polymer "mushrooms". In the denser polymer "brush" regime, protein stabilization decreases back to a value indistinguishable from the bulk solution, consistent with low protein adsorption on dense, collapsed brushes. The temperature-dependent kinetics measured by Fast Relaxation Imaging reveals that PNIPAM does not affect the overall folding/unfolding mechanism. Based on the different stabilizations of two mutants and the relaxation kinetics, we hypothesize that the polymer acts mainly by increasing the conformational entropy of the folded protein by interacting with the protein surface and less by crowding the unfolded state of PGK.

Background: Systemic chemotherapy and targeted agents are associated with various cutaneous toxicities. Even though cutaneous toxicities are manageable, it often results in treatment discontinuation and worsens the patients' quality of life., Aim: The study aimed to determine the spectrum of cutaneous toxicities in patients receiving systemic chemotherapy and targeted agents for breast cancer patients., Patients and Methods: A total of 250 out of 720 patients with breast cancer who developed various cutaneous toxicities to chemotherapeutic or targeted agents were included in the study., Results: Among 250 patients, 57 patients were on neoadjuvant chemotherapy, 89 patients were on adjuvant chemotherapy, 68 were on palliative chemotherapy for metastatic breast cancer and 36 were on targeted treatment for metastatic breast cancer. The most frequently affected site was hair (96%), followed by skin (92%), nail (34%), and mucosa (26%). The most common dermatological toxicity noticed in our study involved the hair in the form of chemotherapy induced alopecia (anagen effluvium) in 93.6%, followed by skin toxicity with generalized xerosis in 92% and, nail toxicity in 34%, and mucosal toxicity in 26%. The most common chemotherapeutic agent which caused frequent cutaneous toxicities in our patients was docetaxel followed by paclitaxel, capecitabine, doxorubicin, epirubicine, cyclophosphamide, 5-flurouracil and targeted agents like lapatinib, everolimus, and tamoxifen., Conclusion: Cutaneous toxicities are common following systemic chemotherapy and targeted agents. Early recognition of cutaneous side effects of these agents and prompt early interventions can reduce the significant morbidity, cosmetic disfigurement, unnecessary treatment interruptions, and psychological distress in women treated for breast cancers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Theory, computation and experiment have matched up for the folding of small proteins in vitro, a difficult feat because folding energy landscapes are fairly smooth and free energy differences between states are small. Smoothness means that protein structure and folding are susceptible to the local environment inside living cells. Theory, computation and experiment are now exploring cellular modulation of energy landscapes. Interesting concepts have emerged, such as co-evolution of protein surfaces with their cellular environment to reduce detrimental interactions. Here we look at very recent work beginning to bring together theory, simulations and experiments in the area of protein landscape modulation, to see what problems might be solved in the near future by combining these approaches., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cyclea peltata is one of the herbs mentioned in ancient scriptures of Ayurveda and is used in different types of Ayurvedic gritham preparations. Moreover, in traditional/tribal medicine C. peltata is used as digestive, anti-inflammatory, diuretic and to treat jaundice, digestive disorders, etc. OBJECTIVE: Activity guided fractionation of C. peltata and in correlation with the levels of bioactive compound tetrandrine., Materials and Methods: Preliminary phytochemical screening, estimation of total alkaloid content, preparation of different extracts of C. peltata (crude extract CP, hexane extract HCP, chloroform extract CCP, methanol extract MCP, alkaloid fraction ACP). In vitro anti-inflammatory studies using RAW 264.7 cells and in vitro antioxidant assays of the different extracts of C. peltata. HPTLC estimation of tetrandrine (TET) was carried out using solvent system toluene: ethyl acetate: diethylamine (7.2: 2: 0.8) and isolation of TET from ACP., Results: Preliminary phytochemical studies of C. peltata showed the presence of alkaloid content in all extracts. Whereas, saponins, steroids and terpenoids were detected in CP and CCP. ACP and TET showed significant in vitro anti-inflammatory and antioxidant activity when compared to other extracts. ACP and TET (100 μg/ml) treatment significantly inhibited the mRNA expression of iNOS, COX-2, TNF-α in LPS treated RAW 264.7 cells. HPTLC estimation of bioactive compound tetrandrine was highest in ACP-228.4 μg/mg followed by CP-29.62 μg/mg, CCP-23.46 μg/mg, MCP-18.82 μg/mg and HCP-1.25 μg/mg. TET has been isolated from ACP., Conclusion: The results of the present in vitro assays revealed that the alkaloid fraction (ACP) is the most active fraction when compared to other extracts and has a positive correlation with the levels of bioactive compound tetrandrine., (Copyright © 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

The introduction of the trialkylsilylethynyl group to the acene core is known to predominantly transform the herringbone structure of pentacene to a slip-stacked packing. However, herein, the occurrence of an unforeseen polymorph of 6,13-bis(trimethylsilylethynyl)pentacene (TMS-pentacene), with an atypical γ-herringbone packing arrangement, is reported. Intermolecular noncovalent interactions in the γ-herringbone polymorph are determined from Hirshfeld surface and quantum theory of atoms-in-molecules (QTAIM) analyses. Furthermore, a comparative truncated symmetry-adapted perturbation theory (SAPT(0)) energy decomposition analysis discloses the role of exchange repulsions that govern molecular packing in the γ-herringbone polymorph. Moreover, the computationally predicted electronic coupling and anisotropic mobility reveal the possibility of enhanced hole transport (μ h =3.7 cm 2  V -1  s -1 ) in the γ-herringbone polymorph, in contrast to the reported polymorph with a hole mobility of μ h =0.1 cm 2  V -1  s -1 ., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Side-chains at the imidic position of naphthalimide rendered a firm control over (i) the degrees of π-π overlap and (ii) distances between the perylenimide units in a crystalline naphthalimide-perylenimide dyad as determined using single crystal XRD and Hirshfeld surface analyses. Steady-state and time-resolved electronic spectroscopy in addition to DFT calculations revealed a decline in intermolecular excitonic interaction due to interfering alkyl chains.

The basioccipital skull base is an extremely rare site for meningoencephalocele. The herniation of the brainstem or part of it through a basioccipital defect is even rarer. We report a case of rhombencephalomeningocele associated with a tethered dermoid. An extensive literature search revealed no such case report of basioccipital cranial dysraphism so far presenting with cranial nerve palsy., (© 2016 S. Karger AG, Basel.)

Objective: To evaluate the hepatoprotective and antioxidant properties of alkaloid extract of Cyclea peltata (C. peltata) against paracetamol/carbon tetra chloride induced liver damage in Wistar rats., Methods: In vivo paracetamol/carbon tetrachloride induced liver damage in Wistar rats, in vitro free radical scavenging studies, HPTLC estimation of tetrandrine and direct analysis in real time- mass spectrometry of alkaloid extract of C. peltata were used for the validation., Results: The results showed that pretreatment with alkaloid extract of C. peltata caused significant reduction of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, serum alkaline phosphatase, serum cholesterol, liver malondialdehyde levels. The reduced glutathione, catalase, superoxide dismutase levels in liver were increased with alkaloid extract of C. peltata treatment. These results were almost comparable to silymarin and normal control. Histopathological studies also substantiated the biochemical findings. The in vitro hydroxyl, superoxide and DPPH scavenging study of alkaloid extract of C. peltata showed significant free radical scavenging property., Conclusions: The hepatoprotective property of alkaloid extract of C. peltata against paracetamol/carbon tetrachloride may be due the synergistic action of alkaloids especially tetrandrine, fangchinoline through free radical scavenging and thus preventing oxidative stress.

Objectives: We studied oral cancer incidence and mortality and the impact of compliance to repeat screening rounds during a 15-year follow-up in a cluster-randomized controlled trial in Trivandrum district, Kerala, India., Methods: Healthy individuals aged 35 and above in seven clusters randomized to the intervention arm received four rounds of oral visual inspection by trained health workers at 3-year intervals, and those in six clusters randomized to the control arm received routine care during 1996-2005 and one round of visual screening during 2006-2009. Screen-positive persons were referred for diagnosis and treatment. Oral cancer incidence and mortality were compared between the study arms by intention to treat analysis., Results: Of the 96,517 eligible subjects in the intervention arm, 25,144 (26.1%) had one, 22,382 (23.2%) had two, 22,008 (22.8%) had three and 19,288 (20.0%) had four rounds of screening. Of the 95,356 eligible subjects in the control group 43,992 (46.1%) received one round of screening. Although the 12% reduction in oral cancer mortality in all individuals did not reach statistical significance, there was a 24% reduction in oral cancer mortality (95% CI 3-40%) in users of tobacco and/or alcohol in the intervention arm after 4-rounds of screening; there was 38% reduction in oral cancer incidence (95% CI 8-59%) and 81% reduction in oral cancer mortality (95% CI 69-89%) in tobacco and/or alcohol users adhering to four screening rounds., Conclusion: Sustained reduction in oral cancer mortality during the 15-year follow-up, with larger reductions in those adhering to repeated screening rounds support the introduction of population-based screening programs targeting users of smoking or chewing tobacco or alcohol or both in high-incidence countries., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Prey capture and digestion in Nepenthes spp. through their leaf-evolved biological traps involve a sequence of exciting events. Sugar-rich nectar, aroma chemicals, narcotic alkaloid secretions, slippery wax crystals, and other biochemicals take part in attracting, capturing, and digesting preys in Nepenthes pitchers. Here we report the distribution of three potent naphthoquinones in Nepenthes khasiana and their roles in prey capture. Plumbagin was first detected in N. khasiana, and its content (root: 1.33 ± 0.02%, dry wt.) was the highest found in any natural source. Chitin induction enhanced plumbagin levels in N. khasiana (root: 2.17 ± 0.02%, dry wt.). Potted N. khasiana plants with limited growth of roots and aerial parts, showed higher levels of plumbagin accumulation (root: 1.92 ± 0.02%; root, chitin induction: 3.30 ± 0.21%, dry wt.) compared with field plants. Plumbagin, a known toxin, insect ecdysis inhibitor, and antimicrobial, was also found embedded in the waxy layers at the top prey capture region of N. khasiana pitchers. Chitin induction, mimicking prey capture, produced droserone and 5-O-methyl droserone in N. khasiana pitcher fluid. Both these naphthoquinone derivatives provide antimicrobial protection to the pitcher fluid from visiting preys. A two-way barrier was found between plumbagin and its two derivatives. Plumbagin was never detected in the pitcher fluid whereas both its derivatives were only found in the pitcher fluid on chitin induction or prey capture. The three naphthoquinones, plumbagin, droserone, and 5-O-methyl droserone, act as molecular triggers in prey capture and digestion in the carnivorous plant, N. khasiana.

A cluster randomized controlled trial was initiated in the Trivandrum district (Kerala, India) on January 1, 2006, to evaluate whether three rounds of triennial clinical breast examination (CBE) can reduce the incidence rate of advanced disease incidence and breast cancer mortality. A total of 275 clusters that included 115,652 healthy women, aged 30-69 years, were randomly allocated to intervention (CBE; 133 clusters; 55,844 women) or control (no screening; 142 clusters; 59,808 women) groups. Performance characteristics (sensitivity, specificity, false-positive rate, and positive predictive value) of CBE were evaluated. An intention-to-treat analysis was performed for comparison of incidence rates between the intervention and control groups. Preliminary results for incidence are based on follow-up until May 31, 2009, when the first round of screening was completed. Of the 50,366 women who underwent CBE, 30 breast cancers were detected among 2880 women with suspicious findings in CBE screening that warranted further investigations. Sensitivity, specificity, false-positive rate, and positive predictive value of CBE were 51.7% (95% confidence interval [CI] = 38.2% to 65.0%), 94.3% (95% CI = 94.1% to 94.5%), 5.7% (95% CI = 5.5% to 5.9%), and 1.0% (95% CI = 0.7% to 1.5%), respectively. The age-standardized incidence rates for early-stage (stage IIA or lower) breast cancer were 18.8 and 8.1 per 100,000 women and for advanced-stage (stage IIB or higher) breast cancer were 19.6 and 21.7 per 100,000 women, in the intervention and control groups, respectively.