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In type 2 diabetes (T2D), the dawn phenomenon is an overnight glucose rise recognized to contribute to overall glycemia and is a potential target for therapeutic intervention. Existing CGM-based approaches do not account for sensor error, which can mask the true extent of the dawn phenomenon. To address this challenge, we developed a probabilistic framework that incorporates sensor error to assign a probability to the occurrence of dawn phenomenon. In contrast, the current approaches label glucose fluctuations as dawn phenomena as a binary yes/no. We compared the proposed probabilistic model with a standard binary model on CGM data from 173 participants (71% female, 87% Hispanic/Latino, 54 ± 12 years, with either a diagnosis of T2D for six months or with an elevated risk of T2D) stratified by HbA 1c levels into normal but at risk for T2D, with pre-T2D, or with non-insulin-treated T2D. The probabilistic model revealed a higher dawn phenomenon frequency in T2D [49% (95% CI 37-63%)] compared to pre-T2D [36% (95% CI 31-48%), p = 0.01] and at-risk participants [34% (95% CI 27-39%), p < 0.0001]. While these trends were also found using the binary approach, the probabilistic model identified significantly greater dawn phenomenon frequency than the traditional binary model across all three HbA 1c sub-groups (p < 0.0001), indicating its potential to detect the dawn phenomenon earlier across diabetes risk categories., (© 2024. The Author(s).)

Digital phenotyping refers to characterizing human bio-behavior through wearables, personal devices, and digital health technologies. Digital phenotyping in populations facing a disproportionate burden of type 2 diabetes (T2D) and health disparities continues to lag compared to other populations. Here, we report our study demonstrating the application of multimodal digital phenotyping, i.e., the simultaneous use of CGM, physical activity monitors, and meal tracking in Hispanic/Latino individuals with or at risk of T2D. For 14 days, 36 Hispanic/Latino adults (28 female, 14 with non-insulin treated T2D) wore a continuous glucose monitor (CGM) and a physical activity monitor (Actigraph) while simultaneously logging meals using the MyFitnessPal app. We model meal events and daily digital biomarkers representing diet, physical activity choices, and corresponding glycemic response. We develop a digital biomarker for meal events that differentiates meal events into normal and elevated categories. We examine the contribution of daily digital biomarkers of elevated meal event count and step count on daily time-in-range 54-140 mg/dL (TIR 54-140 ) and average glucose. After adjusting for step count, a change in elevated meal event count from zero to two decreases TIR 54-140 by 4.0% (p = 0.003). An increase in 1000 steps in post-meal step count also reduces the meal event glucose response by 641 min mg/dL (p = 0.0006) and reduces the odds of an elevated meal event by 55% (p < 0.0001). The proposed meal event digital biomarkers may provide an opportunity for non-pharmacologic interventions for Hispanic/Latino adults facing a disproportionate burden of T2D., (© 2024. The Author(s).)

In light of the high and rising prevalence of obesity, we studied females and males aged 25-54 years with excess weight in the Kolkata metropolitan region, one of India's main cities, to understand the perception, environmental determinants and health complications of obesity. We resorted to primary fieldwork. The close-ended quantitative survey questionnaire was designed to capture the perception and health complications of the sampled population, while a semi-structured interview guide comprising open-ended questions was prepared to capture the target population's in-depth views. Following the WHO guidelines on BMI and WC cut-off for Asian adults, the sampled population comprised females and males aged 25-54 with a waist circumference of 80 cm and 90 cm or higher, respectively, and a BMI of 25 or higher in the Kolkata metropolitan area. Using a concurrent mixed methods approach, we collected and analysed quantitative and qualitative data separately using descriptive statistics and inductive coding before combining them. In the study area, we completed 120 surveys and 18 in-depth interviews. Some environmental factors promoting obesity were the lack of access to healthy, fresh foods, lack of health awareness programmes, advertisements, and weather conditions in Kolkata. Interview participants also extended their concerns about food adulteration and the food industry. Participants confirmed that obesity could increase the risk of developing diabetes, hypertension, cholesterol and heart disease. Further, participants felt squatting was challenging for them. Hypertension was the most common existing health complication found among the study participants. Participants suggested raising awareness, promoting and making access to healthy food and wellness programs more accessible, and regulating fast foods and sugary beverages at institutional, community and social/public policy levels to prevent obesity. Health education and better policies are required to combat obesity and related complications., (© 2023. The Author(s).)

Indian basil (Ocimum basillicum), lemongrass (Cymbopogon flexuosus) and coriander (Coriandrum sativum) leaves are a good source of aromatic oils; however, their extraction volume is low. Hence, two pre-treatment systems (ohmic-heating and ultrasonic) were devised for extraction of essential oils (EO) from the leaves of these three plant spp., which consequently enhanced the EO yield and saved the time and energy. First of all, an experimental set-up was developed for ohmic-heating pre-treatment which was subjected to the optimization of electric conductivity of lemongrass and coriander leaves at 26.25 V/cm and for Indian basil at 22.5 V/cm voltage gradient. An Experimental setup was also developed for ohmic heating-assisted hydro-distillation (OHD). Finally, conventional Clevenger hydro-distillation (CHD), OHD, ultrasonic-assisted conventional hydro-distillation (UACHD) and ultrasonic-assisted ohmic-heating hydro-distillation (UAOHD) methods were evaluated for their effectiveness in the extraction of the EOs. The OHD took 3.5 h time with 410 W power consumption compared to 5 h time and 500 W power consumption in CHD of sleeted leaves. Likewise, a saving of ~ 86% in time and 74% in energy consumption was observed for EO extraction through UAOHD over CHD. Quantity of EOs extracted from all three aromatic plant spp. leaves followed the trend of UAOHD > UACHD > OHD > CHD methods, respectively. Overall, ultrasonic pre-treatment coupled with ohmic-heating assisted hydro-distillation (UAOHD) proved as an innovative and effective clean EO extraction technology which took shorter extraction time and lesser energy consumption with better EO yield over the UACHD, OHD and CHD methods from the leaves of Indian basil, lemongrass and coriander., (© 2023. The Author(s).)

Rho-associated coiled-coil containing protein kinase 1 (ROCK1) intracellular cell signaling pathway regulates cell morphology, polarity, and cytoskeletal remodeling. We observed the activation of ROCK1/myosin light chain (MLC2) signaling pathway in buffalopox virus (BPXV) infected Vero cells. ROCK1 depletion by siRNA and specific small molecule chemical inhibitors (Thiazovivin and Y27632) resulted in a reduced BPXV replication, as evidenced by reductions in viral mRNA/protein synthesis, genome copy numbers and progeny virus particles. Further, we demonstrated that ROCK1 inhibition promotes deadenylation of viral mRNA (mRNA decay), mediated via inhibiting interaction with PABP [(poly(A)-binding protein] and enhancing the expression of CCR4-NOT (a multi-protein complex that plays an important role in deadenylation of mRNA). In addition, ROCK1/MLC2 mediated cell contraction, and perinuclear accumulation of p-MLC2 was shown to positively correlate with viral mRNA/protein synthesis. Finally, it was demonstrated that the long-term sequential passage (P = 50) of BPXV in the presence of Thiazovivin does not select for any drug-resistant virus variants. In conclusion, ROCK1/MLC2 cell signaling pathway facilitates BPXV replication by preventing viral mRNA decay and that the inhibitors targeting this pathway may have novel therapeutic effects against buffalopox., (© 2022. The Author(s).)

Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a retrospective study of 357 unrelated affected individuals, diagnosed with retinal disorders who underwent clinical ES. Variants from ES were filtered, prioritized, and classified using the ACMG recommendations. Clinical diagnosis of the individuals included rod-cone dystrophy (60%), macular dystrophy (20%), cone-rod dystrophy (9%), cone dystrophy (4%) and other phenotypes (7%). Majority of the cases (74%) were singletons and 6% were trios. A confirmed molecular diagnosis was obtained in 24% of cases. In 6% of cases, two pathogenic variants were identified with phase unknown, bringing the potential molecular diagnostic rate to ~ 30%. Including the variants of uncertain significance (VUS), potentially significant findings were reported in 57% of cases. Among cases with a confirmed molecular diagnosis, variants in EYS, ABCA4, USH2A, KIZ, CERKL, DHDDS, PROM1, NR2E3, CNGB1, ABCC6, PRPH2, RHO, PRPF31, PRPF8, SNRNP200, RP1, CHM, RPGR were identified in more than one affected individual. Our results support the utility of clinical ES in the diagnosis of genetically heterogeneous retinal disorders., (© 2022. The Author(s).)

Chemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody-drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of NRs for specific targeting and synergistic treatments of human epidermal growth factor receptor 2 (HER2) positive breast cancer cells. ADNs were designed by first synthesizing ~ 95 nm diameter × ~ 500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. The surface of PTXNRs was functionalized at 2' OH nucleophilic site using carbonyldiimidazole and conjugated to TTZ through the lysine residue interaction forming PTXNR-TTZ conjugates (ADNs). The size, shape, and surface charge of ADNs were characterized using scanning electron microscopy (SEM), SEM, and zeta potential, respectively. Using fluorophore labeling and response surface analysis, the percentage conjugation efficiency was found > 95% with a PTX to TTZ mass ratio of 4 (molar ratio ≈ 682). In vitro therapeutic efficiency of PTXNR-TTZ was evaluated in two HER2 positive breast cancer cell lines: BT-474 and SK-BR-3, and a HER2 negative MDA-MB-231 breast cancer cell using MTT assay. PTXNR-TTZ inhibited > 80% of BT-474 and SK-BR-3 cells at a higher efficiency than individual PTX and TTZ treatments alone after 72 h. A combination index analysis indicated a synergistic combination of PTXNR-TTZ compared with the doses of single-drug treatment. Relatively lower cytotoxicity was observed in MCF-10A human breast epithelial cell control. The molecular mechanisms of PTXNR-TTZ were investigated using cell cycle and Western blot analyses. The cell cycle analysis showed PTXNR-TTZ arrested > 80% of BT-474 breast cancer cells in the G2/M phase, while > 70% of untreated cells were found in the G0/G1 phase indicating that G2/M arrest induced apoptosis. A similar percentage of G2/M arrested cells was found to induce caspase-dependent apoptosis in PTXNR-TTZ treated BT-474 cells as revealed using Western blot analysis. PTXNR-TTZ treated BT-474 cells showed ~ 1.3, 1.4, and 1.6-fold higher expressions of cleaved caspase-9, cytochrome C, and cleaved caspase-3, respectively than untreated cells, indicating up-regulation of caspase-dependent activation of apoptotic pathways. The PTXNR-TTZ ADN represents a novel nanoparticle design that holds promise for targeted and efficient anti-cancer therapy by selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest.

Monogalactosyldiacylglycerol (MGDG) is the most abundant type of glycoglycerolipid found in the plant cell membrane and mostly in the chloroplast thylakoid membrane. The amphiphilic nature of MGDG is attractive in pharmaceutical fields for interaction with other biological molecules and hence exerting therapeutic anti-cancer, anti-viral, and anti-inflammatory activities. In this study, we investigated the therapeutic efficacy of cyanobacteria derived MGDG to inhibit breast cancer cell growth. MGDG was extracted from a cyanobacteria Synechocystis sp. PCC 6803 followed by a subsequent fractionation by column chromatographic technique. The purity and molecular structure of MGDG were analyzed by nuclear magnetic resonance (NMR) spectroscopy analysis. The presence of MGDG in the extracted fraction was further confirmed and quantified by high-performance liquid chromatography (HPLC). The anti-proliferation activity of the extracted MGDG molecule was tested against BT-474 and MDA-MB-231 breast cancer cell lines. The in vitro study showed that MGDG extracted from Synechocystis sp. PCC 6803 induced apoptosis in (70 ± 8) % of BT-474 (p < 0.001) and (58 ± 5) % of MDA-MB-231 cells (p < 0.001) using ~ 60 and 200 ng/ml of concentrations, respectively. The half-maximal inhibitory concentration, IC 50 of MGDG extracted from Synechocystis sp. PCC 6803 were (27.2 ± 7.6) and (150 ± 70) ng/ml in BT-474 and MDA-MB-231 cell lines, respectively. Quantification of caspase-3/7 activity using flow cytometry showed (3.0 ± 0.4) and (2.1 ± 0.04)-fold (p < 0.001) higher protein expressions in the MGDG treated BT-474 and MDA-MB-231 cells, respectively than untreated controls conferring to the caspase-dependent apoptosis. The MGDG did not show any significant cytotoxic side effects in human dermal fibroblasts cells. A commercially available MGDG control did not induce any apoptotic cell death in cancer cells substantiating the potential of the MGDG extracted from Synechocystis sp. PCC 6803 for the treatment of breast cancer cells through the apoptosis-mediated pathway.

The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H 2 O 2 ). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H 2 O 2 . In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H 2 O 2 -treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dose-dependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration [Formula: see text] 0.01 [Formula: see text] ([Formula: see text]). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications.

The presence of endotoxin, also known as lipopolysaccharides (LPS), as a side product appears to be a major drawback for the production of certain biomolecules that are essential for research, pharmaceutical, and industrial applications. In the biotechnology industry, gram-negative bacteria (e.g., Escherichia coli) are widely used to produce recombinant products such as proteins, plasmid DNAs and vaccines. These products are contaminated with LPS, which may cause side effects when administered to animals or humans. Purification of LPS often suffers from product loss. For this reason, special attention must be paid when purifying proteins aiming a product as free as possible of LPS with high product recovery. Although there are a number of methods for removing LPS, the question about how LPS removal can be carried out in an efficient and economical way is still one of the most intriguing issues and has no satisfactory solution yet. In this work, polymeric poly-ε-caprolactone (PCL) nanoparticles (NPs) (d P  = 780 ± 285 nm) were synthesized at a relatively low cost and demonstrated to possess sufficient binding sites for LPS adsorption and removal with ~100% protein recovery. The PCL NPs removed greater than 90% LPS from protein solutions suspended in water using only one milligram (mg) of NPs, which was equivalent to ~1.5 × 10 6 endotoxin units (EU) per mg of particle. The LPS removal efficacy increased to a higher level (~100%) when phosphate buffered saline (PBS containing 137 mM NaCl) was used as a protein suspending medium in place of water, reflecting positive effects of increasing ionic strength on LPS binding interactions and adsorption. The results further showed that the PCL NPs not only achieved 100% LPS removal but also ~100% protein recovery for a wide concentration range from 20-1000 μg/ml of protein solutions. The NPs were highly effective in different buffers and pHs. To scale up the process further, PCL NPs were incorporated into a supporting cellulose membrane which promoted LPS adsorption further up to ~100% just by running the LPS-containing water through the membrane under gravity. Its adsorption capacity was 2.8 × 10 6 mg of PCL NPs, approximately 2 -fold higher than that of NPs alone. This is the first demonstration of endotoxin separation with high protein recovery using polymer NPs and the NP-based portable filters, which provide strong adsorptive interactions for LPS removal from protein solutions. Additional features of these NPs and membranes are biocompatible (environment friendly) recyclable after repeated elution and adsorption with no significant changes in LPS removal efficiencies. The results indicate that PCL NPs are an effective LPS adsorbent in powder and membrane forms, which have great potential to be employed in large-scale applications.

VSe 2 is a transition metal dichaclogenide which has a charge- density wave transition that has been well studied. We report on a low-temperature upturn in the resistivity and, at temperatures below this resistivity minimum, an unusual magnetoresistance which is negative at low fields and positive at higher fields, in single crystals of VSe 2 . The negative magnetoresistance has a parabolic dependence on the magnetic field and shows little angular dependence. The magnetoresistance at temperatures above the resistivity minimum is always positive. We interpret these results as signatures of the Kondo effect in VSe 2 . An upturn in the susceptibility indicates the presence of interlayer V ions which can provide the localized magnetic moments required for scattering the conduction electrons in the Kondo effect. The low-temperature behaviour of the heat capacity, including a high value of γ, along with a deviation from a Curie-Weiss law observed in the low-temperature magnetic susceptibility, are consistent with the presence of magnetic interactions between the paramagnetic interlayer V ions and a Kondo screening of these V moments.

The objective of this study was to determine the presence of ciprofloxacin and pharmacokinetics of ciprofloxacin in blood plasma of broiler chicken after single oral administration at feeding state. Ciprofloxacin was administered orally at 10 mg kg(-1) to each of the 10 broiler chickens at feeding state. Presence of ciprofloxacin was determined by TLC method and pharmacokinetics by HPLC method. Peak plasma concentration (Cmax) of ciprofloxacin, 0.26±0.03 mg l(-1) was achieved at 4.40±0.1 h (Tmax). Biological half-life of ciprofloxacin was 5.25±0.02 h. Area under the curve (AUC) was 13.397±0.13 mg ml(-1) h, elimination rate constant was 0.13±0.02 h(-1), volume of distribution was 0.194±0.04 l kg(-1) and bioavailability was 49±0.48%. On the basis of the results of the present study, we conclude that, feeding state may have a vital effect on the pharmacokinetic profile of ciprofloxacin in broiler blood plasma.

To search a proper dopant to further improve superconductivity in 11 type Fe-based superconductors makes sense to both their superconductivity mechanism and possible technological applications. In present work, Mg doped FeSe polycrystalline bulks were obtained by a two-step solid-state reaction method. Even though there are many MgSe and iron impurities existing in the Mg heavy doped FeSe bulks, they exhibit obviously increased Tc compared to undoped FeSe sample. It was found that Mg addition has little effect on the crystal lattice parameters of superconducting β-FeSe, whereas leads to the formation of nano-layered grain structure consisted of MgSe and β-FeSe with similar X-ray diffraction characteristics. Lots of nano-structural interfaces between FeSe and MgSe formed in this homogenous layered grain structure have significant effect on the superconducting properties and are responsible for the enhancement of Tc, as like the case of FeSe thin film on some specific substrates. Our work not only demonstrates a powerful way for raising Tc in bulk superconductors, but also provides a well-defined platform for systematic studies of the mechanism of unconventional superconductivity by considering interface effect.

The relationship between family size and income and the biochemical indices of 242 children (aged from 5 to 12 years) from five schools in Dhaka City, Bangladesh, was investigated. Socio-economic data were collected by questionnaire and blood samples were drawn by visiting each school on a prefixed date. Mean levels of all measures, except for serum zinc, fell within the normal range. Older boys, but not girls (10-12 years of age) had statistically significantly higher haemoglobin, serum protein and serum vitamin A levels compared with those of the younger boys (5-9 years of age). The children were divided into three family size groups (small, up to 4 members; medium, 5-7 members; and large, 8 or more) to investigate the effect of family size on the biochemical data. The children from smaller families showed significantly higher levels of haemoglobin and serum vitamin A compared with the children from large families. For serum protein, copper and zinc, there was no statistically significant difference between the children of different family size groups. To analyse the effect of family income, children were divided into three income groups (low, up to taka 2000; medium, taka 2001-4500; and high, 4501 or more). The children from the low family income group had significantly lower serum protein (7.5 g/100 ml) and haemoglobin (13.4 g/100 ml) levels compared with those of the children from the high family income group (for protein, 7.7 g/100 ml and haemoglobin, 14.1 g/100 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between socio-demographic variables and growth of 242 school children from five schools in Dhaka city, Bangladesh, was investigated. The socio-demographic data were collected by questionnaire and the anthropometric data were collected by visits to each school on a prefixed date. Children from the high-family-income group showed significantly higher body weight, height, MUAC, SFT, wt/age, and ht/age compared with children from the low-family-income group. When the effect of age, sex, father's occupation and family size were adjusted for by means of multiple analysis of variance, the family income still showed a significant contribution to the variation in the anthropometric indices of these children. These findings suggest that family income makes a significant contribution as a determinant of growth of urban school children in Bangladesh.