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Spanning across Bangladesh and India, the Sundarban Delta consists of over a thousand islands, the majority of which are protected. These islands are important for the rich biodiversity and unique species found here. However, these islands are also at the forefront of climate change due to the impact of rising sea levels and extreme weather events. Therefore, we analyzed the long-term transformations in the land use land cover (LULC) between 1999 and 2020. We used a variety of geostatistical methods, including optimized hot spots cold spots and join count statistics, to examine the spatial patterns of changes in LULC across the study area. The results of our analysis revealed substantial changes in the spatial patterns of mangroves and pond aquaculture. The changes revealed a distinct north-south demarcation in spatial patterns, in the form of clustering of mangroves in the uninhabited islands located in the south and pond aquaculture clustered in the northern inhabited islands. The loss of area under mangroves was concentrated in the southern edges of the islands, which were most exposed to erosion in the open ocean. Nevertheless, we observed an increase in the area under mangroves in some of the northern riverine islands (17 km 2 ). In the case of pond aquaculture, it was mostly concentrated in inhabited islands in the north. Most of the expansions were concentrated in the Indian part of the delta (631 km 2 ). It is noteworthy that because of effective conservation measures, there was very limited overlap between mangroves and pond aquaculture, denoting the conversion of agricultural land to pond aquaculture instead of mangroves. Thus, the results of our study revealed the importance of local level conservation policies and anthropogenic activities, such as deforestation and local level disturbance like over-extraction of water and pollution, on the changing patterns of LULC across this unique, fragile ecosystem. Future studies may incorporate a finer resolution time series of LULC changes over time and space to enable more detailed analysis., (© 2024. The Author(s).)

Adherent cells ensure membrane homeostasis during de-adhesion by various mechanisms, including endocytosis. Although mechano-chemical feedbacks involved in this process have been studied, the step-by-step build-up and resolution of the mechanical changes by endocytosis are poorly understood. To investigate this, we studied the de-adhesion of HeLa cells using a combination of interference reflection microscopy, optical trapping and fluorescence experiments. We found that de-adhesion enhanced membrane height fluctuations of the basal membrane in the presence of an intact cortex. A reduction in the tether force was also noted at the apical side. However, membrane fluctuations reveal phases of an initial drop in effective tension followed by saturation. The area fractions of early (Rab5-labelled) and recycling (Rab4-labelled) endosomes, as well as transferrin-labelled pits close to the basal plasma membrane, also transiently increased. On blocking dynamin-dependent scission of endocytic pits, the regulation of fluctuations was not blocked, but knocking down AP2-dependent pit formation stopped the tension recovery. Interestingly, the regulation could not be suppressed by ATP or cholesterol depletion individually but was arrested by depleting both. The data strongly supports Clathrin and AP2-dependent pit-formation to be central to the reduction in fluctuations confirmed by super-resolution microscopy. Furthermore, we propose that cholesterol-dependent pits spontaneously regulate tension under ATP-depleted conditions., (© 2024. The Author(s).)

Purpose: A subset of common variable immunodeficiency (CVID) patients either presents with or develops autoimmune and lymphoproliferative complications, such as granulomatous lymphocytic interstitial lung disease (GLILD), a major cause of morbidity and mortality in CVID. While a myriad of phenotypic lymphocyte derangements has been associated with and described in GLILD, defects in T and B cell antigen receptor (TCR/BCR) signaling in CVID and CVID with GLILD (CVID/GLILD) remain undefined, hindering discovery of biomarkers for disease monitoring, prognostic prediction, and personalized medicine approaches., Methods: To identify perturbations of immune cell subsets and TCR/BCR signal transduction, we applied mass cytometry analysis to peripheral blood mononuclear cells (PBMCs) from healthy control participants (HC), CVID, and CVID/GLILD patients., Results: Patients with CVID, regardless of GLILD status, had increased frequency of HLADR + CD4 + T cells, CD57 + CD8 + T cells, and CD21 lo B cells when compared to healthy controls. Within these cellular populations in CVID/GLILD patients only, engagement of T or B cell antigen receptors resulted in discordant downstream signaling responses compared to CVID. In CVID/GLILD patients, CD21 lo B cells showed perturbed BCR-mediated phospholipase C gamma and extracellular signal-regulated kinase activation, while HLADR + CD4 + T cells and CD57 + CD8 + T cells displayed disrupted TCR-mediated activation of kinases most proximal to the receptor., Conclusion: Both CVID and CVID/GLILD patients demonstrate an activated T and B cell phenotype compared to HC. However, only CVID/GLILD patients exhibit altered TCR/BCR signaling in the activated lymphocyte subsets. These findings contribute to our understanding of the mechanisms of immune dysregulation in CVID with GLILD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The objective of this paper was to develop a computer-aided diagnostic (CAD) tools for automated analysis of capsule endoscopic (CE) images, more precisely, detect small intestinal abnormalities like bleeding., Methods: In particular, we explore a convolutional neural network (CNN)-based deep learning framework to identify bleeding and non-bleeding CE images, where a pre-trained AlexNet neural network is used to train a transfer learning CNN that carries out the identification. Moreover, bleeding zones in a bleeding-identified image are also delineated using deep learning-based semantic segmentation that leverages a SegNet deep neural network., Results: To evaluate the performance of the proposed framework, we carry out experiments on two publicly available clinical datasets and achieve a 98.49% and 88.39% F1 score, respectively, on the capsule endoscopy.org and KID datasets. For bleeding zone identification, 94.42% global accuracy and 90.69% weighted intersection over union (IoU) are achieved., Conclusion: Finally, our performance results are compared to other recently developed state-of-the-art methods, and consistent performance advances are demonstrated in terms of performance measures for bleeding image and bleeding zone detection. Relative to the present and established practice of manual inspection and annotation of CE images by a physician, our framework enables considerable annotation time and human labor savings in bleeding detection in CE images, while providing the additional benefits of bleeding zone delineation and increased detection accuracy. Moreover, the overall cost of CE enabled by our framework will also be much lower due to the reduction of manual labor, which can make CE affordable for a larger population., (© 2021. Society for Imaging Informatics in Medicine.)

Intracerebroventricular (ICV) injection of streptozotocin (STZ) is a well established procedure to induce neuroinflammation leading to dementia in experimental animals. However, the optimal dose of STZ has not been determined. In the present study, rats were ICV injected with 1.5, 3 and 6 mg of STZ per kg of body weight. After 21 days, neuroinflammatory markers i.e. TNF-α, IL-1β, ROS and nitrite were quantified in the hippocampus. Memory function was assessed by the radial arm maze test after 9, 12, 15, 18, 21 days following STZ injection. STZ treatment significantly increased neuroinflammatory markers and decreased memory functions in a dose dependent manner showing optimum effects at the dose of 3 mg/kg.

In the original article the typesetter made several errors. Figures 7 and 9 are incorrect. Following are the correct figures.

Otolaryngological conditions constitute a major share of emergency medical problem among children. The present study was conducted to assess the patient profiles, incidences morbidities, mode of presentation and managements of different otolaryngological emergencies among pediatric patients presented in a tertiary care hospital. Descriptive cross-sectional study by analysing retrospectively collected information pertaining to the patients attended ENT emergency service department of a tertiary care hospital, Kolkata. Data were collected using predesigned proforma and were analysed with the help of SPSS version 20. About 39.0% of total ENT emergency attendance was contributed by pediatric age group. The male female ratio was 1:1.33 with average age of 58.95 ± 34.42 (mean ± SD) months. Half of the attendees had ear problem and almost one-third reported complaints related to nose. The major complaints at the time of presentation were earache (32.3%), nasal foreign body (24.0%) and aural foreign body (13.3%) closely followed by aero-digestive tract foreign body (12.0%). Inflammatory conditions affected the ears more, foreign bodies found most commonly in nose and miscellaneous condition such as impacted wax was found to be related to ear in significantly higher proportion. Conservative management was provided to 96.25% of patients. Foreign body insertion was found to be associated with lower age group. Most of the emergencies were managed conservatively which might be done at subdivision or district level to reduce the undesirable burden on the tertiary care medical colleges., Competing Interests: Compliance with Ethical StandardsThere is no conflict of interest among the authors.

Chemical injury by alkali burn is a major cause of corneal blindness in the clinical setting. Current management advocates multiple therapies aimed to prevent inflammation, initiate quick re-epithelialization, arrest the fibrosis, and avoid dry eye and pain by using bandage contact lenses. We hypothesized sustained delivery of the anti-inflammatory, antifibrotic drug pirfenidone through vitamin E-loaded contact lenses as a logical single approach to counter the pathology involved. Vitamin E particles were created in situ in commercial silicon hydrogel contact lenses by soaking the lenses in a vitamin E-ethanol solution. The vitamin E-laden lenses were then placed into pirfenidone-saline solution to load the drug into the lens. The contact lenses were evaluated by both in vitro and in vivo means. For in vitro, lenses were placed into 3 mL of saline solution. The concentration of pirfenidone released was measured by UV-vis spectrophotometry. The contact lenses were implanted in rabbit eyes following the alkali burn; the drug availability in the aqueous humor was evaluated by HPLC at various time points 10 min, 30 min, 2 h, and 3 h; and gene expression of inflammatory cytokines IL-1β, TNF-α, and TGF-β1 was evaluated in the cornea at the end of the study period. In another group of rabbits inflicted with alkali injury, the corneas were graded after 7 days of contact lens implantation with and without pirfenidone. A mathematical model was developed for delivery of the drug to the cornea and aqueous humor after a contact lens is inserted in the eye. The model was validated with experimental data and used to determine the bioavailability both for contact lenses and eye drops. In vitro release of unmodified commercial contact lenses saw a release time of approximately 20 min, with a partition coefficient of 2.68 ± 0.06. The release of pirfenidone from 20% vitamin E-loaded lenses saw a release time of approximately 80 min, with a partition coefficient of 4.20 ±  0.04. In vivo, the drug was available in the aqueous humor for up to 3 h. Gene expression of inflammatory cytokine IL-β1 and profibrotic growth factor TGF-β1 was significantly suppressed in corneas treated with pirfenidone contact lenses. A week after the alkali burn, the eyes with pirfenidone contact lenses showed significant improvement in corneal haze in comparison to the control eyes. About 50% of the drug loaded in the lens reached the aqueous humor compared to 1.3% with eye drops. Vitamin E-loaded contact lenses serve as a suitable platform for delivery of pirfenidone following alkali burn in rabbit eyes; positive pre-clinical outcome identifies it as promising therapy for addressing corneal inflammation and fibrosis. The bioavailability is about 40-fold higher for contact lenses compared to that for eye drops.

The antioxidants in food materials have recently attracted researchers' attention because many reports have shown that the oxidative stress is closely related to the aging process of the cells and acts as a trigger to various diseases including cancer. Since reactive oxygen species (ROS) is involved in initiating and promoting several diseases such as cancer and cardiovascular events, this study was designed to evaluate the antioxidant capacity of pectic polysaccharides extracted from the bark of Cinnamomum zeylanicum, locally known as Daruchini. An arabinogalactan (A), one partly methyl esterified galacturonic acid (B) and a neutral glucan (C) were isolated. The glucan is made up of β-(1 → 3)-linked glucopyranosyl residues and has a molecular mass of 7 kDa. The arabinogalactan is highly branched and has an average molecular mass of 40 kDa. The in vitro antioxidant capacity of the fractions was studied by ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. The arabinogalactan (A) showed the highest potential followed by the uronic acid (B) and glucan (C). Taken together, these findings demonstrate that these polysaccharides could be used as natural antioxidants by the food industry.

In this whitepaper, the Manufacturing Technical Committee of the Product Quality Research Institute provides information on the common, best practices in use today in the development of high-quality chemistry, manufacturing and controls documentation. Important topics reviewed include International Conference on Harmonization, in vitro-in vivo correlation considerations, quality-by-design approaches, process analytical technologies and current scale-up, and process control and validation practices. It is the hope and intent that this whitepaper will engender expanded dialog on this important subject by the pharmaceutical industry and its regulatory bodies.

The objective of this study was to develop chitosan-based delivery of cobalt oxide nanoparticles to human leukemic cells and investigate their specific induction of apoptosis. The physicochemical properties of the chitosan-coated cobalt oxide nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. The solubility of chitosan-coated cobalt oxide nanoparticles was higher at acidic pH, which helps to release more cobalt ions into the medium. Chitosan-coated cobalt oxide nanoparticles showed good compatibility with normal cells. However, our results showed that exposure of leukemic cells (Jurkat cells) to chitosan-coated cobalt oxide nanoparticles caused an increase in reactive oxygen species generation that was abolished by pretreatment of cells with the reactive oxygen species scavenger N-acetyl-L-cysteine. The apoptosis of Jurkat cells was confirmed by flow-cytometric analysis. Induction of TNF-α secretion was observed from stimulation of Jurkat cells with chitosan-coated cobalt oxide nanoparticles. We also tested the role of TNF-α in the induction of Jurkat cell death in the presence of TNF-α and caspase inhibitors. Treatment of leukemic cells with a blocker had a greater effect on cancer cell viability. From our findings, oxidative stress and caspase activation are involved in cancer cell death induced by chitosan-coated cobalt oxide nanoparticles.

The purpose of this study is to evaluate the prospect of using surface modified cobalt oxide(CoO) nanoparticles as carriers of cancerantigens to human macrophages. N-Phosnomethyliminodiacetic acid (PMIDA) was used for surface modification to overcome the toxic effect of CoO nanoparticles. Here, the phosphonate group of the PMIDA acts as a surface-anchoring agent and the remaining -COOH groups bind nonspecifically with tumor associated antigens. This modification allows the conjugation of human oral carcinoma (KB) cell lysate (CL) as an antigen with PMIDA coated CoO nanoparticles (CL-PMIDA-CoO). Particle characterization was performed by dynamic light scattering, atomic force microscopy, and scanning electron microscopy studies. Fourier transform IR spectroscopy was used to investigate conjugation of the protein with nanoparticles. Protein encapsulation was confirmed by protein gel electrophoresis. Active uptake of antigen-conjugated nanoparticles by macrophages was confirmed by fluorescence microscopy. The antitumor activity of the nanocomplex pulsed macrophages was investigated on a human oral carcinoma cell line (KB) in vitro. The modified nanocomplexes upregulate IFN-γ and TNF-α and induce an anticancer immune response by activating macrophages. The use of TNF-α inhibitor confirmed the ability of the CL-PMIDA-CoO nanocomplex to stimulate TNF-α mediated immunostimulation. CL-PMIDA-CoO nanoparticles efficiently increased the CD4(+) population. Thus, our findings provide insight into the use of PMIDA coated CoO nanoparticles as antigen delivery vehicles.

Feasibility of an irrigation project is evaluated by two criteria viz., reservoir capacity to irrigate its command area and economic returns by incremental crop production versus capital investment for dam construction. The annual water requirement of different crops in the command area is estimated and compared with the availability of water from the dam for irrigation purpose. The annual crop water requirement is estimated as the sum of evapotranspiration for crops and transmission and other losses. Evapotranspiration is estimated by modified Penman formula. Economics of crop production is analyzed by first estimating the monetary value of existing crop production under current rain fed conditions and then estimating the incremental production of irrigated command area for the proposed crop pattern. The proposed cropping pattern is prepared so as to maximize the benefit of crop production and fodder requirement while maintaining a better crop rotation to improve and maintain physical, chemical, and biological conditions of the soil. The dam is to be used for irrigation and water supply only. Command area served by this reservoir will be 76,500 ha. The existing annual agricultural return is Rs. 2995.56 lakhs and with the proposed irrigation scheme, it is estimated as Rs. 1,77,91.90 lakhs. The incremental annual return would be Rs. 1,47,96.35 lakhs i.e., 642.68% increase in annual return.

In this whitepaper, the Manufacturing Technical Committee (MTC) of the Product Quality Research Institute has updated the 1997 Transdermal Drug Delivery Systems Scale-Up and Post Approval Change workshop report findings to add important new product development and control principles. Important topics reviewed include ICH harmonization, quality by design, process analytical technologies, product and process validation, improvements to control of critical excipients, and discussion of Food and Drug Administration's Guidance on Residual Drug in Transdermal and Related Drug Delivery Systems as well as current thinking and trends on in vitro-in vivo correlation considerations for transdermal systems.

Unlabelled: Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine that circumvents immunogenetic restrictions. The currently available vaccine for typhoid is a pure polysaccharide vaccine, immune response to which is T-cell independent. Little is known about whether genetic variation among vaccinees associates with variation in their antibody response to a polysaccharide vaccine. We conducted a study on 1,000 individuals resident in an area at high-risk for typhoid; vaccinated them with the typhoid vaccine, measured their antibody response to the vaccine, assayed >2,000 curated SNPs chosen from 283 genes that are known to participate in immune-response; and analyzed these data using a strategy to (a) minimize the statistical problems associated with testing of multiple hypotheses, and (b) internally cross-validate inferences, using a half-sample design, with little loss of statistical power. The first stage analysis, using the first half-sample, identified 54 SNPs in 43 genes to be significantly associated with immune response. In the second-stage, these inferences were cross-validated using the second half-sample. First-stage results of only 8 SNPs (out of 54) in 7 genes (out of 43) were cross-validated. We tested additional SNPs in these 7 genes, and found 8 more SNPs to be significantly associated. Haplotypes constructed with these SNPs in these 7 genes also showed significant association. These 7 genes are DEFB1, TLR1, IL1RL1, CTLA4, MAPK8, CD86 and IL17D. The overall picture that has emerged from this study is that (a) immune response to polysaccharide antigens is qualitatively different from that to protein antigens, and (b) polymorphisms in genes involved in polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signaling and eventual production of antimicrobial peptides are associated with antibody response to the polysaccharide vaccine for typhoid., Electronic Supplementary Material: The online version of this article (doi:10.1007/s11568-010-9134-1) contains supplementary material, which is available to authorized users.

The values of the second dissociation constant p K 2 and related thermodynamic quantities of [N-(2-acetamido)-2-aminoethanesulfonic acid] (ACES) have already been reported over the temperature range 5 to 55°C including 37°C. This paper reports the pa H values of four chloride ion free buffer solutions and eight buffer solutions with I = 0.16 mol·kg -1 , matching closely to that of the physiological sample. Conventional pa H values for all twelve buffer solutions from 5 to 55°C, are reported. The residual liquid junction potential correction for two widely used temperatures, 25 and 37°C, has been made. The flowing-junction calomel cell method has been utilized to measure E j , the liquid junction potential. The operational pH values for four buffer solutions at 25 and 37°C are calculated using the physiological phosphate buffer standard based on NBS/NIST convention. These solutions are recommended as pH standards in the pH range of 6.8 to 7.2 for physiological fluids.

Mixed-ligand ruthenium(II) complexes of three photoactive ligands, viz., (E)-1-[2-(4-methyl-2-pyridyl)-4-pyridyl]-2-(1-naphthyl)-1-ethene (mppne), (E)-1-(9-anthryl)-2-[2-(4-methyl-2-pyridyl)-4-pyridyl]-1-ethene (mppae) and (E)-1-[2-(4-methyl-2-pyridyl)-4-pyridyl]-2-(1-pyrenyl)-1-ethene (mpppe), in which a 2,2'-bipyridyl unit is linked via an ethylinic linkage to either a naphthalene, an anthracene or a pyrene chromophore and three electroactive ligands, viz., 4-(4-pyridyl)-1,2-benzenediol (catpy), 5,6-dihydroxy-1,10-phenanthroline (catphen) and 1,2-benzenediol (cat), were synthesized in good to moderate yields. Complexes [Ru(bpy)(2)(mppne)](2+) (bpy is 2, 2'-bipyridyl), [Ru(bpy)(2)(mppae)](2+), [Ru(bpy)(2)(mpppe)](2+), [Ru(bpy)(2)(sq-py)](+), [Ru(bpy)(2)(sq-phen)](+) and [Ru(phen)(2)(bsq)](+) (phen is 1,10-phenanthroline) were fully characterized by elemental analysis, IR, (1)H NMR, fast-atom bombardment or electron-impact mass, UV-vis and cyclic voltammetric methods. In the latter three complexes, the ligands catpy, catphen and cat are actually bound to the metal center as the corresponding semiquinone species, viz., 4-(4-pyridyl)-1,2-benzenedioleto(+I) (sq-py), 1,10-phenanthroline-5,6-dioleto(+I) (sq-phen) and 1,2-benzenedioleto(+I) (bsq), thus making the overall charge of the complexes formally equal to + 1 in each case. These three complexes are electron paramagnetic resonance active and exhibit an intense absorption band between 941 and 958 nm owing to metal-to-ligand charge transfer (MLCT, d (Ru)-->pi*(sq)) transitions. The other three ruthenium(II) complexes containing three photoactive ligands, mppne, mppae and mpppe, exhibit MLCT (d (Ru)-->pi*(bpy) ) bands in the 454-461-nm region and are diamagnetic. These can be characterized by the (1)H NMR method. [Ru(bpy)(2)(mppne)](2+), [Ru(bpy)(2)(mppae)](2+) and [Ru(bpy)(2)(mpppe)](2+) exhibit redox waves corresponding to the Ru(III)/Ru(II) couple along with the expected ligand (bpy and substituted bpy) based ones in their cyclic and differential pulse voltammograms (CH(3)CN, 0.1 M tetrabutylammonium hexafluorophosphate)-corresponding voltammograms of [Ru(bpy)(2)(sq-py)](+), [Ru(bpy)(2)(sq-phen)](+) and [Ru(phen)(2)(bsq)](+) are mainly characterized by waves corresponding to the quinone/semiquinone (q/sq) and semiquinone/1,2-diol (sq/cat) redox processes. The results of absorption and fluorescence titration as well as thermal denaturation studies reveal that [Ru(bpy)(2)(mppne)](2+) and [Ru(bpy)(2)(mppae)](2+) are moderate-to-strong binders of calf thymus DNA with binding constants ranging from 10(5) to 10(6) M(-1). Under the identical conditions of drug and light dose, the DNA (supercoiled pBR 322) photocleavage activities of these two complexes follow the order:[Ru(bpy)(2)(mppne)](2+)>[Ru(bpy)(2)(mppae)](2+), although the emission quantum yields follow the reverse order. The other ruthenium(II) complexes containing the semiquinone-based ligands are found to be nonluminescent and inefficient photocleavage agents of DNA. However, experiments shows that [Ru(bpy)(2)(sq)](+)-based complexes oxidize the sugar unit and could be used as mild oxidants for the sugar moiety of DNA. Possible explanations for these observations are presented.