AAV mediated repression of Neat1 lncRNA combined with F8 gene augmentation mitigates pathological mediators of joint disease in haemophilia.

Haemophilic arthropathy (HA), a common comorbidity in haemophilic patients leads to joint pain, deformity and reduced quality of life. We have recently demonstrated that a long non-coding RNA, Neat1 as a primary regulator of matrix metalloproteinase (MMP) 3 and MMP13 activity, and its induction in the target joint has a deteriorating effect on articular cartilage. In the present study, we administered an Adeno-associated virus (AAV) 5 vector carrying an short hairpin (sh)RNA to Neat1 via intra-articular injection alone or in conjunction with systemic administration of a capsid-modified AAV8 (K31Q) vector carrying F8 gene (F8-BDD-V3) to study its impact on HA. AAV8K31Q-F8 vector administration at low dose, led to an increase in FVIII activity (16%-28%) in treated mice. We further observed a significant knockdown of Neat1 (~40 fold vs. untreated injured joint, p = 0.005) in joint tissue of treated mice and a downregulation of chondrodegenerative enzymes, MMP3, MMP13 and the inflammatory mediator- cPLA2, in mice receiving combination therapy. These data demonstrate that AAV mediated Neat1 knockdown in combination with F8 gene augmentation can potentially impact mediators of haemophilic joint disease.

Unveiling the potential of membrane in climate change mitigation and environmental resilience in ecosystem.

Carbon capture technologies are becoming increasingly crucial in addressing global climate change issues by lowering CO2 emissions from industrial and power generation activities. Post-combustion carbon capture, which uses membranes instead of adsorbents, has emerged as one of promising and environmentally friendly approaches among these technologies. The operation of membrane technology is based on the premise of selectively separating CO2 from flue gas emissions. This provides a number of different benefits, including improved energy efficiency and decreased costs of operation. Because of its adaptability to changing conditions and its low impact on the surrounding ecosystem, it is an appealing choice for a diverse array of uses. However, there are still issues to be resolved, such as those pertaining to establishing a high selectivity, membrane degradation, and the costs of the necessary materials. In this article, we evaluate and explore the prospective applications and roles of membrane technologies to control climate change by post-combustion carbon capturing. The primary proposition suggests that the utilization of membrane-based carbon capture has the potential to make a substantial impact in mitigating CO2 emissions originating from industrial and power production activities. This is due to its heightened ability to selectively absorb carbon, better efficiency in energy consumption, and its flexibility to various applications. The forthcoming challenges and potential associated with the application of membranes in post-carbon capture are also discussed.

16S rRNA metagenomic profiling of red amaranth grown organically with different composts and soils.

In recent years organic food is gaining popularity as it is believed to promote better human health and improve soil sustainability, but there are apprehensions about pathogens in organic produces. This study was designed to understand the effect of different composts and soils on the status of the microbiome present in organically grown leafy vegetables. 16S rRNA metagenomic profiling of the leaves was done, and data were analyzed. It was found that by adding composts, the OTU of the microbiome in the organic produce was higher than in the conventional produce. The beneficial genera identified across the samples included plant growth promoters (Achromobacter, Paenibacillus, Pseudomonas, Sphingobacterium) and probiotics (Lactobacillus), which were higher in the organic produce. Some pathogenic genera, viz., plant pathogenic bacteria (Cellvibrio, Georgenia) and human pathogenic bacteria (Corynebacterium, Acinetobacter, Streptococcus, Streptomyces) were also found but with relatively low counts in the organic produce. Thus, the present study highlights that organic produce has lesser pathogen contamination than the conventional produce. KEY POINTS: • 16S rRNA metagenomics profiling done for organic red amaranth cultivar • Microbial richness varied with respect to the soil and compost type used • The ratio of beneficial to pathogenic genera improves with the addition of compost.

Physiological and molecular insights into the allelopathic effects on agroecosystems under changing environmental conditions.

Allelopathy is a natural phenomenon of competing and interfering with other plants or microbial growth by synthesizing and releasing the bioactive compounds of plant or microbial origin known as allelochemicals. This is a sub-discipline of chemical ecology concerned with the effects of bioactive compounds produced by plants or microorganisms on the growth, development and distribution of other plants and microorganisms in natural communities or agricultural systems. Allelochemicals have a direct or indirect harmful effect on one plant by others, especially on the development, survivability, growth, and reproduction of species through the production of chemical inhibitors released into the environment. Cultivation systems that take advantage of allelopathic plants' stimulatory/inhibitory effects on plant growth and development while avoiding allelopathic autotoxicity is critical for long-term agricultural development. Allelopathy is one element that defines plant relationships and is involved in weed management, crop protection, and microbial contact. Besides, the allelopathic phenomenon has also been reported in the forest ecosystem; however, its presence depends on the forest type and the surrounding environment. In the present article, major aspects addressed are (1) literature review on the impacts of allelopathy in agroecosystems and underpinning the research gaps, (2) chemical, physiological, and ecological mechanisms of allelopathy, (3) genetic manipulations, plant defense, economic benefits, fate, prospects and challenges of allelopathy. The literature search and consolidation efforts in this article shall pave the way for future research on the potential application of allelopathic interactions across various ecosystems.

The gut ecosystem and immune tolerance.

The gastrointestinal tract is home to the largest microbial population in the human body. The gut microbiota plays significant roles in the development of the gut immune system and has a substantial impact on the maintenance of immune tolerance beginning in early life. These microbes interact with the immune system in a dynamic and interdependent manner. They generate immune signals by presenting a vast repertoire of antigenic determinants and microbial metabolites that influence the development, maturation and maintenance of immunological function and homeostasis. At the same time, both the innate and adaptive immune systems are involved in modulating a stable microbial ecosystem between the commensal and pathogenic microorganisms. Hence, the gut microbial population and the host immune system work together to maintain immune homeostasis synergistically. In susceptible hosts, disruption of such a harmonious state can greatly affect human health and lead to various auto-inflammatory and autoimmune disorders. In this review, we discuss our current understanding of the interactions between the gut microbiota and immunity with an emphasis on: a) important players of gut innate and adaptive immunity; b) the contribution of gut microbial metabolites; and c) the effect of disruption of innate and adaptive immunity as well as alteration of gut microbiome on the molecular mechanisms driving autoimmunity in various autoimmune diseases.

Small molecule-derived pH-gated ion transporters.

The pH regulation of transmembrane ion transport is critical for biological processes and has a direct implication on diseases such as cancer. Synthetic transporters that can be regulated using pH show promise as therapeutic agents. This review highlights the importance of the fundamental principles of acid-base chemistry in achieving pH regulation. A systematic classification of transporters based on the pKa of their pH-responsive units aids in correlating the pH regulation of ion transport with the molecular structure. This review also summarises the applications of these transporters and their efficacy in cancer therapy.

Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats.

Liquiritigenin (LTG) and its bioprecursor isoliquiritigenin(ISL), the main bioactives from roots of Glycyrrhiza genus are progressively documented as a potential pharmacological agent for the management of chronic diseases. The aim of this study was to evaluate the pharmacological potential of liquiritigenin, isoliquiritigenin rich extract of Glycyrrhiza glabra roots (IVT-21) against the production of pro-inflammatory cytokines from activated macrophages as well as further validated the efficacy in collagen-induced arthritis model in rats. We also performed the safety profile of IVT-21 using standard in-vitro and in-vivo assays. Results of this study revealed that the treatment of IVT-21 and its major bioactives (LTG, ISL) was able to reduce the production of pro-inflammatory cytokines (TNF-α, IL-6) in LPS-activated primary peritoneal macrophages in a dose-dependent manner compared with vehicle-alone treated cells without any cytotoxic effect on macrophages. In-vivo efficacy profile against collagen-induced arthritis in Rats revealed that oral administration of IVT-21 significantly reduced the arthritis index, arthritis score, inflammatory mediators level in serum. IVT-21 oral treatment is also able to reduce the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue and mRNA level of pro-inflammatory cytokines in paw tissue in a dose-dependent manner when compared with vehicle treated rats. Acute oral toxicity profile of IVT-21 demonstrated that it is safe up to 2000 mg/kg body weight in experimental mice. This result suggests the suitability of IVT-21 for further study in the management of arthritis and related complications.

Characterization and Energy Densification of Mayhaw Jelly Production Wastes Using Hydrothermal Carbonization.

Research background: Mayhaw jelly, made from mayhaw berries from the southern United States, is a popular food product that on processing produces a berry pomace waste. Little information is available in the literature about this waste or how to valorize it. This study investigated this food production waste and its possibilities for conversion to a biofuel. Experimental approach: Dried mayhaw berry wastes were characterized with fiber analysis using the US National Renewable Energy Laboratory methods. After drying and grinding, hydrothermal carbonization was applied to the mayhaw berry wastes, the mayhaw waste without seeds, and mayhaw waste seeds. Fourier transform infrared spectroscopy (FTIR) was performed on mayhaw berry wastes, mayhaw waste without seeds, and mayhaw waste seeds. Calorimetry revealed the fuel value of each component of the waste and of the dried mayhaw berry wastes without any component separated. Friability testing on pellets of the biomass investigated their durability. Results and conclusions: Fiber analysis indicated a high proportion of lignin compared to cellulose in the dried mayhaw waste. Hydrothermal carbonization did not enhance the fuel value of the seeds due to their tough outer coat that inhibited hydrothermal carbonization's high ionic-product water penetration. Other mayhaw berry waste samples had enhanced fuel value after treatment at 180 or 250 °C for 5 min, with a higher fuel value attained for 250 °C treatment. After hydrothermal carbonization, the wastes were easily pelletized into durable pellets. Fourier transform infrared spectroscopy characterization indicated raw seeds had high lignin content, as did the hydrothermal carbonization-treated mayhaw berry wastes. Novelty and scientific contribution: Hydrothermal carbonization is a process not previously applied to mayhaw berry wastes. This study fills in the gaps of this waste biomass' potential to become a biofuel.

Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.

Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe2+) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml-1), carotenoid accumulation (1.96-2.08 µg ml-1), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm-1) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.

BAHD acetyltransferase contributes to wound-induced biosynthesis of oleo-gum resin triterpenes in Boswellia.

Triterpenes (30-carbon isoprene compounds) represent a large and highly diverse class of natural products that play various physiological functions in plants. The triterpene biosynthetic enzymes, particularly those catalyzing the late-stage regio-selective modifications are not well characterized. The bark of select Boswellia trees, e.g., B. serrata exudes specialized oleo-gum resin in response to wounding, which is enriched with boswellic acids (BAs), a unique class of C3α-epimeric pentacyclic triterpenes with medicinal properties. The bark possesses a network of resin secretory structures comprised of vertical and horizontal resin canals, and amount of BAs in bark increases considerably in response to wounding. To investigate BA biosynthetic enzymes, we conducted tissue-specific transcriptome profiling and identified a wound-responsive BAHD acetyltransferase (BsAT1) of B. serrata catalyzing the late-stage C3α-O-acetylation reactions in the BA biosynthetic pathway. BsAT1 catalyzed C3α-O-acetylation of αBA, ßBA, and 11-keto-ßBA in vitro and in planta assays to produce all the major C3α-O-acetyl-BAs (3-acetyl-αBA, 3-acetyl-ßBA, and 3-acetyl-11-keto-ßBA) found in B. serrata bark and oleo-gum resin. BsAT1 showed strict specificity for BA scaffold, whereas it did not acetylate the more common C3ß-epimeric pentacyclic triterpenes. The analysis of steady-state kinetics using various BAs revealed distinct substrate affinity and catalytic efficiency. BsAT1 transcript expression coincides with increased levels of C3α-O-acetyl-BAs in bark in response to wounding, suggesting a role of BsAT1 in wound-induced biosynthesis of C3α-O-acetyl-BAs. Overall, the results provide new insights into the biosynthesis of principal chemical constituents of Boswellia oleo-gum resin.

The 2022 outbreak and the pathobiology of the monkeypox virus.

Following two reports of monkeypox virus infection in individuals who returned from Nigeria to the USA, one who returned to Texas (July 2021) and the other to the Washington, DC area (November 2021), the number of monkeypox infection have dramatically increased. This sounded an alarm of potential for spreading of the virus throughout the USA. During 2022, there was a report of monkeypox virus infection (May 6, 2022) in a British national following a visit to Nigeria who developed readily recognizable signs and symptoms of monkeypox virus infection. Soon following this report, case numbers climbed. By June 10, 2022, more than 1,500 cases were reported in 43 countries, including Europe and North America. While the prevalence of the monkeypox virus is well known in central and western Africa, its presence in the developed world has raised disturbing signs for worldwide spread. While infection was reported during the past half-century, starting in the Democratic Republic of Congo in 1970, in the United States, only sporadic monkeypox cases have been reported. All cases have been linked to international travel or through African animal imports. The monkeypox virus is transmitted through contact with infected skin, body fluids, or respiratory droplets. The virus spreads from oral and nasopharyngeal fluid exchanges or by intradermal injection; then rapidly replicates at the inoculation site with spreads to adjacent lymph nodes. Monkeypox disease begins with constitutional symptoms that include fever, chills, headache, muscle aches, backache, and fatigue. Phylogenetically the virus has two clades. One clade emerged from West Africa and the other in the Congo Basin of Central Africa. During the most recent outbreak, the identity of the reservoir host or the primary carriage remains unknown. African rodents are the suspected intermediate hosts. At the same time, the Centers for Disease Control (CDC) affirmed that there are no specific treatments for the 2022 monkeypox virus infection; existing antivirals shown to be effective against smallpox may slow monkeypox spread. A smallpox vaccine JYNNEOS (Imvamune or Imvanex) may also be used to prevent infection. The World Health Organization (WHO), has warned that the world could be facing a formidable infectious disease challenge in light of the current status of worldwide affairs. These affairs include the SARS-COVID-19 pandemic and the Ukraine-Russia war. In addition, the recent rise in case of numbers worldwide could continue to pose an international threat. With this in mind, strategies to mitigate the spread of monkeypox virus are warranted.

Infection of human microglial cell line CHME-3 to study neuropathogenesis of chikungunya virus.

Chikungunya virus (CHIKV) infection, generally characterised by fever, rash and debilitating polyarthralgia, and/or arthritis, also causes complications of the central nervous system, including encephalitis. However, the role of microglial cells in the neuropathogenesis of CHIKV is poorly understood. The current study characterised the progression of CHIKV infection in the human microglial cell line CHME-3. The susceptibility of these cells to CHIKV and the viral replication kinetics were assessed during the early and late phases of infection. The cell viability was determined using the cell viability assay. Ultrastructural changes in CHIKV infected CHME-3 cells were assessed using transmission electron microscopy. The results showed that CHME-3 cells are susceptible to CHIKV infection and support viral replication with no significant loss in cell viability until 72 h post infection. Ultrastructural studies revealed the formation of cytopathic vacuoles-I (CPV-I) in the early stages and CPV-II in later stages with several virions organized along the membrane of CPV-II. Profuse vacuolation was observed in the later stages of infection. Abnormal giant mitochondria with altered cristae were observed in infected cells with an electron-dense matrix. The study establishes CHME-3 cells as a potential model for investigating the role of human microglial cells in neuropathogenicity of CHIKV.

Diffusion measurements of hydrocarbons in H-MCM-41 extrudates with pulsed-field gradient nuclear magnetic resonance spectroscopy.

Mesoporous materials are promising catalysts for production of biofuels. Herein, H-MCM-41 catalysts with different concentrations of the silica Bindzil binder (10-50 wt%) were prepared and characterized using pulsed-field gradient (PFG) NMR in the powder form and as extrudates. Effective diffusion coefficients (De) are measured in all cases. Diffusivities of n-hexadecane were found smaller for extrudates as compared to the powder catalysts. The estimates of diffusive tortuosity were also determined. PFG NMR data showed one major component that reveals diffusion in interconnected meso- and micropores and one other minor component (1-2%) that may correspond to more isolated pores or may represent complex effects of restricted diffusion. Therefore, several approaches including initial slope analysis of spin-echo attenuation curves, two-component fitting and Laplace inversion were used to discuss different aspects of diffusional transport in the studied H-MCM-41 materials. Correlations between De and the amount of Bindzil, the specific surface area, the micropore volume, the particle size, the total acid sites and the Lewis acid sites are discussed.

Detection of unprecedented level of antibiotic resistance and identification of antibiotic resistance factors, including QRDR mutations in Escherichia coli isolated from commercial chickens from North India.

AIM: This study aimed to investigate the occurrence of antibiotic resistance phenotype and simultaneously understand its genetic basis in Escherichia coli isolated from the cloacal swabs of commercial chickens from north India. METHODS AND RESULTS: Escherichia coli isolates were assessed for susceptibility to 14 different antibiotics using the disc-diffusion technique and were screened for the presence of 22 antibiotic resistance genes (ARGs) by employing PCR. Isolates were found to be highly resistant to fluoroquinolones (nalidixic acid 91%, norfloxacin 73% and ciprofloxacin 66%), tetracycline (71%), beta-lactams (ampicillin 49% and amoxicillin/clavulanic acid 37%), co-trimoxazole (48%), streptomycin (31%) and chloramphenicol (28%); and comparatively less resistant to cefazolin (13%), amikacin (10%), aztreonam (4%), gentamicin (4%) and ceftriaxone (3%). Sixty-three percent of isolates were resistant to more than four different drugs. Abundance of plasmid-borne ARGs like tetA (83%), sul3 (44%), aadA1 (44%), strA (43%), strB (41%), qnrS (38%), sul2 (28%) and aac(6)-Ib-cr (15%) was observed among the isolates. Forty-five percent of isolates possessed more than five different ARGs. Quinolone resistance-determining region (QRDR) mutations within gyrA and parC genes were found to be the major determiners of quinolone resistance. QRDR mutations included leu83, asn87 and gly87 within gyrase-A polypeptide and ile80 and lys84 within topoisomerase IV (encoded by parC). CONCLUSIONS: Our findings suggest the abuse of antibiotics as feed additives and prophylactic drugs in Indian poultry sector. It also projects this industry as an active hotspot for the replication and selection of ARGs. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings would provide evidence to the authorities for formulating effective strategies for restricting antibiotic usage as non-therapeutic agents in food animals. Occurrence of both plasmid-borne and chromosome-borne resistance towards quinolones can drive movement of resistance phenotype across bacterial species and vertical movement of resistance along the bacterial generations, respectively, which can pose mitigation challenges.

Inflammatory Bowel Disease Therapeutics: A Focus on Probiotic Engineering.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of gastrointestinal (GI) tract with dysregulated mucosal immune functions and disturbed commensal ecosystem of the intestinal lumen. IBD is categorized into two major subsets: Crohn's disease (CD) and ulcerative colitis (UC). Though advent of biologics has shifted the treatment with relatively longer remission compared to small molecule pharmaceuticals, patients still suffer from long-term complications. Since gut-microbiome is now accepted as another human organ holding potential for long-lasting human health, probiotics, and its engineering hold great promises to treat several previously untreatable chronic inflammatory conditions including IBD. Several emerging biological engineering tools have unlimited potential to manipulate probiotic bacterial system. These can produce useful therapeutic biologics with a goal to either ameliorate and/or treat previously untreatable chronic inflammatory conditions. As gut-microbiome is diverse and vary in different ethnic, geographic, and cultural human population, it will be important to develop vision for personalized probiotic treatment and develop the technology thereof to make personalized probiotic options a reality. The aim of this review paper is to present an overview of the current knowledge on both pharmacological and nonpharmacological IBD treatment modalities with a special emphasis on probiotic strains that are developed through the probiotic engineering. These engineered probiotics contain the most anti-inflammatory cytokines found within the human immune response and are currently being used to treat the intestinal inflammation in IBD for the IBD treatment.

Challenges and prospects of neurosurgical teleconsultations in a developing country: a reality check.

OBJECTIVE: The adoption of telemedicine became a necessity during the COVID-19 pandemic because patients found commuting to be difficult owing to travel restrictions. Initially, audio-based teleconsultations were provided. Later, on the basis of the feedback of patients and caregivers, the authors started to provide video-based teleconsultations via WhatsApp. The authors subsequently surveyed the patients and caregivers to determine their satisfaction levels with telemedicine services. METHODS: An anonymized telephone survey of patients who had participated in teleconsultation was conducted with a structured questionnaire. The responses were analyzed and their correlations with the perceived benefits and limitations of audio and video teleconsultation were determined. RESULTS: Three hundred respondents were included in the first round of surveys, of whom 250 (83.3%) consented to video teleconsultation. Among the respondents who participated in both audio and video teleconsultations (n = 250), paired analysis showed that video teleconsultation was perceived as better in terms of providing easier access to healthcare services (p < 0.001), saving time (p < 0.001), and satisfaction with the way patient needs were conveyed to healthcare providers (p = 0.023), as well as in terms of adequacy of addressing healthcare needs (p < 0.001) and consequently providing a higher rate of overall satisfaction (p < 0.001). For both audio and video teleconsultation, overall patient satisfaction was significantly related to only previous exposure to WhatsApp. However, for video consultation, longer call duration (p = 0.023) was an important independent factor. Video teleconsultation was preferable to face-to-face consultation irrespective of educational status, but higher education was associated with preference for video teleconsultation. CONCLUSIONS: Both audio and video teleconsultation are viable cost-effective surrogates for in-person physical neurosurgical consultation. Although audio teleconsultation is more user-friendly and is not restricted by educational status, video teleconsultation trumps the former owing to a more efficient and satisfactory doctor-to-patient interface.

A Systematic Review on the Current Trend in Nonsurgical Aesthetic Training for Knowledge, Skill, and Professional Identity Formation.

BACKGROUND: Non-surgical aesthetics is a rapidly growing healthcare domain and lacks pedagogically sound education and training programs. The trainee physicians often participate in short courses which are outside of the scope of an existing postgraduate training program to acquire the necessary knowledge and procedural skills. However, such training programs lack values and interests that shape critical thinking and holistic decision-making, often referred to as professional identity. OBJECTIVES: This systematic review aims to analyze current trends in non-surgical aesthetic clinical education to form knowledge, skills, and professional identity. METHODS: A detailed literature search was conducted in electronic databases-PubMed, Cochrane, Centre for Reviews and Dissemination, and Google Scholar-for relevant studies published between January 2010 and December 2020, with an update in September 2021. RESULTS: Fifty-five articles were identified through electronic searches, among which 40 were selected following a review of the abstracts. Sixteen articles were identified as the best evidence for the detailed and iterative review based on their relevance and fit to the inclusion criteria. Unfortunately, none of the included studies designed their questionnaire based on the Kirkpatrick Model, which is best known for analyzing and evaluating the results of training and educational programs. CONCLUSIONS: This systematic review provides valuable insight into graduate professional identity formation and graduates' readiness for independent clinical practice. Therefore, particular consideration should be given to incorporating these triggers when developing evidence-based postgraduate curricula for non-surgical aesthetics.

Optimization, fabrication, and characterization of four electrode-based sensors for blood impedance measurement.

In this work, an optimized, non-invasive four electrode-based impedimetric sensors have been designed, fabricated, and characterized for measuring the impedance of a biological cell. The impedimetric sensors having four mono-polar electrodes were fabricated utilizing the photolithography technique with gold as the electrode material. Furthermore, the impedance of the electrolyte/electrode interface was simulated by optimizing different parameters, including applied voltage, PBS thickness, and diameter, using COMSOL Multiphysics software for a frequency range of 100 Hz to 1 MHz. Next, the impedance of the fabricated device was measured experimentally using the electrochemical impedance spectroscopy (EIS) technique. Then, the COMSOL data was equated with the impedance obtained from the fabricated devices to realize the feasibility and error percentage (RSE < 5%) of the sensor. The equivalent circuit model for the measured impedance data of PBS was obtained utilizing the ZsimpWin software. Besides, the mathematical relations between the impedance, phase angle and the area of the electrode were interpreted for the fabricated impedimetric sensors. Later on, a real blood sample was also characterized to demonstrate the feasibility and the validity of the proposed technique and the fabricated devices in cell diagnosis.

Aedes aegypti lachesin protein binds to the domain III of envelop protein of Dengue virus-2 and inhibits viral replication.

Dengue virus (DENV) comprises of four serotypes (DENV-1 to -4) and is medically one of the most important arboviruses (arthropod-borne virus). DENV infection is a major human health burden and is transmitted between humans by the insect vector, Aedes aegypti. Ae. aegypti ingests DENV while feeding on infected humans, which traverses through its gut, haemolymph and salivary glands of the mosquito before being injected into a healthy human. During this process of transmission, DENV must interact with many proteins of the insect vector, which are important for its successful transmission. Our study focused on the identification and characterisation of interacting protein partners in Ae. aegypti to DENV. Since domain III (DIII) of envelope protein (E) is exposed on the virion surface and is involved in virus entry into various cells, we performed phage display library screening against domain III of the envelope protein (EDIII) of DENV-2. A peptide sequence showing similarity to lachesin protein was found interacting with EDIII. The lachesin protein was cloned, heterologously expressed, purified and used for in vitro interaction studies. Lachesin protein interacted with EDIII and also with DENV. Further, lachesin protein was localised in neuronal cells of different organs of Ae. aegypti by confocal microscopy. Blocking of lachesin protein in Ae. aegypti with anti-lachesin antibody resulted in a significant reduction in DENV replication.

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder.

OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.