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1.
Cureus ; 16(3): e55942, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38601398

RESUMO

Background Diarrhea is a major public health problem in under-five children worldwide. Various sociodemographic, environmental, and behavioral factors play a role in the occurrence of diarrheal disease in children under the age of five. This study aims to estimate the cumulative incidence of acute diarrheal diseases during a one-year study period and examine its association with the built environment factors among children under the age of five in selected underprivileged areas of Bhopal. Methodology We conducted this study in Bhopal, a city in central India. We surveyed the underprivileged dwellers of Vajpayee Nagar, Sanjay Nagar, and Mother India Colony of Bhopal city. This is a prospective cohort study with a one-year follow-up period to examine the cumulative incidence of acute diarrheal diseases among under-five-year-old children in the study area. Data were analyzed using SPSS version 25 (IBM Corp., Armonk, NY, USA). Results Data were collected from February 2021 to February 2022. A total of 658 families of eligible children were contacted to participate in the study. After excluding 38 participants for various reasons (denied consent: 3; lost to follow-up: 32; moved out of the study area: 3), data were finally analyzed for 620 participants. In the study among the under-five-year-old children, the cumulative incidence of acute diarrheal diseases was 23.8% (148 out of 620). In our study, lower age (adjusted odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, p = 0.041) and non-availability of flush latrine in the house (adjusted OR = 4.95, 95% CI = 1.80-13.59, p = 0.002) were statistically associated with a higher incidence of acute diarrheal disease among the study population. Conclusions In our investigation, we observed a cumulative incidence of diarrhea at 23.8% (148 out of 620) among the underprivileged under-five population residing in Bhopal, India. This incidence exhibited significant associations with younger age and the absence of in-house flush latrines.

2.
Mol Pharm ; 20(12): 6090-6103, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37963105

RESUMO

Short-interfering RNA (siRNA) oligonucleotide therapeutics that modify gene expression by accessing RNA-interference (RNAi) pathways have great promise for the treatment of a range of disorders; however, their application in clinical settings has been limited by significant challenges in cellular delivery. Herein, we report a structure-function study using a series of modified cyclic amphipathic cell-penetrating peptides (CAPs) to determine the impact of peptide sequence on (1) siRNA-binding efficiency, (2) cellular delivery and knockdown efficiency, and (3) the endocytic uptake mechanism. Nine cyclic peptides of the general sequence Ac-C[XZ]4CG-NH2 in which X residues are hydrophobic/aromatic (Phe, Tyr, Trp, or Leu) and Z residues are charged/hydrophilic (Arg, Lys, Ser, or Glu) are assessed along with one acyclic peptide, Ac-(WR)4G-NH2. Cyclization is enforced by intramolecular disulfide bond formation between the flanking Cys residues. Binding analyses indicate that strong cationic character and the presence of aromatic residues that are competent to participate in CH-π interactions lead to CAP sequences that most effectively interact with siRNA. CAP-siRNA binding increases in the following order as a function of CAP hydrophobic/aromatic content: His < Phe < Tyr < Trp. Both cationic charge and disulfide-constrained cyclization of CAPs improve uptake of siRNA in vitro. Net neutral CAPs and an acyclic peptide demonstrate less-efficient siRNA translocation compared to the cyclic, cationic CAPs tested. All CAPs tested facilitated efficient siRNA target gene knockdown of at least 50% (as effective as a lipofectamine control), with the best CAPs enabling >80% knockdown. Significantly, gene knockdown efficiency does not strongly correlate with CAP-siRNA internalization efficiency but moderately correlates with CAP-siRNA-binding affinity. Finally, utilization of small-molecule inhibitors and targeted knockdown of essential endocytic pathway proteins indicate that most CAP-siRNA nanoparticles facilitate siRNA delivery through clathrin- and caveolin-mediated endocytosis. These results provide insight into the design principles for CAPs to facilitate siRNA delivery and the mechanisms by which these peptides translocate siRNA into cells. These studies also demonstrate the nature of the relationships between peptide-siRNA binding, cellular delivery of siRNA cargo, and functional gene knockdown. Strong correlations between these properties are not always observed, which illustrates the complexity in the design of optimal next-generation materials for oligonucleotide delivery.


Assuntos
Peptídeos Penetradores de Células , Peptídeos Cíclicos , Peptídeos Cíclicos/química , RNA Interferente Pequeno/química , Técnicas de Silenciamento de Genes , Peptídeos Penetradores de Células/química , Oligonucleotídeos , Dissulfetos
3.
Cureus ; 15(10): e46637, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37937030

RESUMO

INTRODUCTION: Tuberculosis (TB) is a major public health problem in the developing world. Depression affects medicine adherence in TB patients. There is a scarcity of data regarding the prevalence of depression among TB patients from any city in central India. Therefore, the aim of this research was to study the prevalence of depression and associated factors in TB patients in the Vidisha district of Madhya Pradesh, India. METHODS: This was a cross-sectional study conducted on 106 TB patients visiting the TB and chest outpatient department of Atal Bihari Vajpayee Government Medical College (ABVGMC). It is a tertiary health care facility located in the district of Vidisha in Madhya Pradesh, India. Data collection was done from September 2020 to January 2021. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9). We used a semi-structured questionnaire to collect data regarding relevant demographic and behavioral factors. Analyses were done in IBM SPSS software, version 25 (IBM Corp., Armonk, NY). RESULTS: The prevalence of depression among TB patients was 55.7% (n = 59). Depression in the mild category was most common (n = 44, 41.5%), followed by moderate (n = 10, 9.4%), and the moderately severe (n = 5, 4.7%) category. Depression prevalence was found to be slightly more common in females (58.5% vs. 52.8% in males), married participants (58.2% vs. 51.3% in unmarried), educated more than high school (56.8% vs. 54.8% in less than high school), socioeconomically Above Poverty Line (APL) (60.5% vs. 52.4% in Below Poverty Line (BPL)), living in urban areas (60.9% vs. 47.6% in rural areas), and in the continuation phase of anti-TB treatment (58.6% vs. 52.1% in intensive phase), but differences were statistically non-significant. Depression was significantly associated with the medicine non-adherence group (vs. the medicine adherence group; p-value: 0.022) and the previously treated TB patient category (vs. the new case group; p-value: 0.031). CONCLUSION: The prevalence of depression among TB patients was very high (55.7%). The prevalence of depression was significantly higher in the medicine non-adherent group (p-value: 0.022) and the previously treated TB patient group (p-value: 0.031). In this study, we have not found any significant association between the prevalence of depression among TB patients and sex, marital status, education attainment, poverty status, or living in an urban or rural areas.

5.
Mar Pollut Bull ; 192: 115003, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37178643

RESUMO

Cambay rift basin is the only geothermal province in India that hosts several saline thermal water manifestations having EC values varying from 525 to 10,860 µS/cm. Various ionic ratios (Na/Cl, Br/Cl, Ca/(SO4 + HCO3), SO4/Cl) as well as boron isotopic composition (δ11B = 40.5 to 46 ‰) clearly ascribes the presence of fossil (relics of evaporated seawater) seawater as origin of increased salinity in the majority of thermal waters. Depleted isotopic (δ18O, δ2H) composition of these thermal waters also substantiates the presence of paleowater in these systems. In rest of the thermal waters, agricultural return flow is found to be source of dissolved solutes as confirmed from different bivariate plots such as B/Cl vs. Br/Cl and δ11B vs. B/Cl as well as from ionic ratios. This study thus provides the diagnostic tools to elucidate the source of variable salinity in the thermal waters circulating in the Cambay rift basin, India.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental , Isótopos/análise , Água do Mar/química , Índia , Salinidade , Água Subterrânea/química , Poluentes Químicos da Água/análise
6.
bioRxiv ; 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37090604

RESUMO

Brain computation depends on intricately connected yet highly distributed neural networks. Due to the absence of the requisite technologies, causally testing fundamental hypotheses on the nature of inter-areal processing have remained largely out-of-each. Here we developed the first two photon holographic mesoscope, a system capable of simultaneously reading and writing neural activity patterns with single cell resolution across large regions of the brain. We demonstrate the precise photo-activation of spatial and temporal sequences of neurons in one brain area while reading out the downstream effect in several other regions. Investigators can use this new platform to understand feed-forward and feed-back processing in distributed neural circuits with single cell precision for the first time.

7.
medRxiv ; 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37034695

RESUMO

Purpose: To identify characteristics of SARS-CoV-2 infection that are associated with hospitalization in children initially evaluated in a Pediatric Emergency Department (ED). Methods: We identified cases of SARS-CoV-2 positive patients seen in the Arkansas Children's Hospital (ACH) ED or hospitalized between May 27, 2020, and April 28, 2022 using ICD-10 codes within the Pediatric Hospital Information System (PHIS) Database. We compared infection waves for differences in patient characteristics, and used logistic regressions to examine which characteristics led to a higher chance of hospitalization. Findings: We included 681 pre-Delta cases, 673 Delta cases, and 970 Omicron cases. Almost 17% of patients were admitted to the hospital. Compared to Omicron infected children, pre-Delta and Delta infected children were twice as likely to be hospitalized (OR=2.2 and 2.0, respectively; p<0.0001). Infants less than 1 year of age were >3 times as likely to be hospitalized than children ages 5-14 years regardless of wave (OR=3.42; 95%CI=2.36-4.94). Rural children were almost 3 times as likely than urban children to be hospitalized across all waves (OR=2.73; 95%CI=1.97-3.78). Finally, those with a complex condition had nearly a 15-fold increase in odds of admission (OR=14.6; 95%CI=10.6-20.0). Conclusions: Children diagnosed during the pre-Delta or Delta waves were more likely to be hospitalized than those diagnosed during the Omicron wave. Younger and rural patients were more likely to be hospitalized regardless of wave. We suspect lower vaccination rates and larger distances from medical care influenced higher hospitalization rates.

8.
Microbiol Resour Announc ; 12(3): e0000723, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36779742

RESUMO

An eleven-year-old tested positive for SARS-CoV-2 Lambda variant. Sequencing was performed on the Oxford Nanopore and the Illumina NextSeq 500. Both platforms identified all 7 of the synonymous mutations in the sample, while all 28 nonsynonymous mutations were identified from Oxford Nanopore and 20 nonsynonymous mutations were identified from Illumina.

9.
Int J STD AIDS ; 34(4): 266-272, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36634248

RESUMO

INTRODUCTION: Thyroid dysfunction is one of the most common endocrine disorders in people living with HIV (PLHIV). The abnormality in thyroid function has been linked with the adverse effects of prolonged antiretroviral therapy (ART) in PLHIV, but its prevalence remains obscure. The present study aimed to determine the prevalence of impaired thyroid function and its relationship to ART duration in Nepalese people living with HIV. METHODS: This cross-sectional clinical laboratory based study was conducted at SRL Diagnostics Nepal, Pvt. Ltd. from October 2021 to May 2022. Two hundred and three HIV-seropositive patients enrolled at Tribhuvan University Teaching Hospital (TUTH) in Kathmandu, Nepal were examined for their thyroid function test (TFT) by analyzing the serum T3, T4, and TSH concentrations using a fully automated COBAS e411 analyzer (Roche Diagnostics, USA) based on the electrochemiluminescence assay (ECLIA). RESULTS: Out of 203 PLHIV, 22 (10.83%) had a thyroid disorder, with subclinical hypothyroidism (n = 16, 72.73%) being the most common, followed by subclinical hyperthyroidism (n = 3, 13.63%). Thyroid dysfunction had no significant correlation with HIV/ART duration (p = 0.304) and sex (p = 0.419), whereas, the risk of thyroid dysfunction was induced with the rise in the age of the PLHIV (p = 0.002, ϕ = 0.274). There were no significant differences in the mean serum T3, T4 and TSH values among different sexes and the HIV/ART duration, however a significant difference in the mean values of TSH (F (3, 199) = 3.231, p = 0.023) and T3 (F (3, 199) = 4.587, p = 0.004) among the different age-groups were shown. The mean T3 values also indicated a gradual decrease with increasing age. CONCLUSION: The study revealed subclinical hypothyroidism as the prevailing thyroid disorder associated with PLHIV. The risk of thyroid dysfunction in PLHIV was neither gender specific nor being attributed by the ART duration in Nepalese population; however, elderly PLHIV were highly susceptible to the risk of thyroid disorder.


Assuntos
Infecções por HIV , Hipotireoidismo , Humanos , Idoso , Estudos Transversais , Nepal/epidemiologia , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Infecções por HIV/tratamento farmacológico , Tireotropina/uso terapêutico
10.
bioRxiv ; 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-36711849

RESUMO

To produce goal-directed eye movements known as saccades, we must channel sensory input from our environment through a process known as sensorimotor transformation. The behavioral output of this phenomenon (an accurate eye movement) is straightforward, but the coordinated activity of neurons underlying its dynamics is not well understood. We searched for a neural correlate of sensorimotor transformation in the activity patterns of simultaneously recorded neurons in the superior colliculus (SC) of three male rhesus monkeys performing a visually guided, delayed saccade task. Neurons in the intermediate layers produce a burst of spikes both following the appearance of a visual (sensory) stimulus and preceding an eye movement command, but many also exhibit a sustained activity level during the intervening time ("delay period"). This sustained activity could be representative of visual processing or motor preparation, along with countless cognitive processes. Using a novel measure we call the Visuomotor Proximity Index (VMPI), we pitted visual and motor signals against each other by measuring the degree to which each session's population activity (as summarized in a low-dimensional framework) could be considered more visual-like or more motor-like. The analysis highlighted two salient features of sensorimotor transformation. One, population activity on average drifted systematically toward a motor-like representation and intermittently reverted to a visual-like representation following a microsaccade. Two, activity patterns that drift to a stronger motor-like representation by the end of the delay period may enable a more rapid initiation of a saccade, substantiating the idea that this movement initiation mechanism is conserved across motor systems.

11.
Cureus ; 15(12): e49951, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38179359

RESUMO

Objective Doppler velocimetry is an established method of antepartum fetal surveillance in pre-eclampsia. Cerebroplacental ratio detects the centralization of fetal blood flow and the insufficiency in placental circulation. It is postulated to be a better marker of perinatal outcome than either vessel Doppler alone. The current study aims to assess the cerebroplacental ratio as a predictor of adverse perinatal outcomes and compare it to the systolic/diastolic (S/D) ratio of umbilical artery (UA) and middle cerebral artery (MCA) in hypertensive disorders of pregnancy. Material and methods The present prospective observational cohort study included 100 patients with hypertensive disorders of pregnancies between 32 and 37 weeks. Ultrasound with Doppler was done and the following parameters were assessed: fetal biometry, amniotic fluid index, umbilical artery pulsatility index, middle cerebral artery pulsatility index, S/D ratio of umbilical artery, S/D ratio of middle cerebral artery, and cerebroplacental ratio. Sensitivity, specificity, positive and negative predictive values were calculated for the cerebroplacental ratio and S/D ratios of umbilical and middle cerebral arteries. McNemar's test was used for the comparison of sensitivity and specificity. Results Thirty-two patients had an abnormal cerebroplacental ratio. Adverse perinatal outcomes such as a cesarean section for fetal distress, small for gestational age, APGAR < 7 at 1 and 5 minutes, NICU admission, and perinatal mortality were more in the group with abnormal cerebraplacental ratio and the difference was statistically significant. Conclusion The cerebroplacental ratio is a more reliable predictor of adverse perinatal outcomes and should be routinely calculated during obstetrical Doppler for antepartum fetal surveillance in case of hypertensive disorders of pregnancy.It suggested that the cerebroplacental ratio may be calibrated in the software ofthe Doppler ultrasonography machine for routine use in high-risk pregnancies.

12.
Chem Asian J ; 17(19): e202200724, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-35986893

RESUMO

Self-assembled peptides are an emerging family of biomaterials that show great promise for a range of biomedical and biotechnological applications. Introducing and tuning the pH-responsiveness of the assembly is highly desirable for improving their biological activities. Inspired by proteins with internal ionizable residues, we report a simple but effective approach to constructing pH-responsive peptide assembly containing unnatural ionic amino acids with an aliphatic tertiary amine side chain. Through a combined experimental and computational investigation, we demonstrate that these residues can be accommodated and stabilized within the internal hydrophobic compartment of the peptide assembly. The hydrophobic microenvironment shifts their pKa significantly from a basic pH typically found for free amines to a more biologically relevant pH in the weakly acidic range. The pH-induced ionization and ionization-dependent self-assembly and disassembly are thoroughly investigated and correlated with the biological activity of the assembly. This new approach has unique advantages in tuning the pH-responsiveness of self-assembled peptides across a large pH range in a complex biological environment. We anticipate the ionizable amino acids developed here can be widely applicable to the synthesis and self-assembly of many amphiphilic peptides with endowed pH-responsive properties to enhance their biological activities toward applications ranging from targeted therapeutic delivery to proton transport.


Assuntos
Aminoácidos , Prótons , Aminas , Materiais Biocompatíveis/química , Concentração de Íons de Hidrogênio , Peptídeos/química
13.
iScience ; 25(9): 104818, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36034228

RESUMO

Osteogenesis imperfecta (OI) is characterized by repeated bone fractures. Recent studies have shown that T lymphocytes and regulatory T cells (Tregs) regulate the functions of osteoclasts and osteoblasts, thus playing a role in bone turnover. We demonstrate an activated effector phenotype and higher secretion of pro-inflammatory cytokines, IFN-γ, and TNF-α in OI peripheral T cells as compared with wild-type (WT). Suppressive Tregs (spleen and thymus) were qualitatively similar, whereas there was a quantitative decrease in OI versus WT. Restoring Treg numbers by systemic transplantation in OI mice resulted in reduced T cell activation and effector cytokine secretion that correlated with significant improvements in tibial trabecular and cortical bone parameters and stiffness of femur, along with increased osteoblast mineralization and decreased osteoclast numbers. Therefore, Tregs can dampen the pro-inflammatory environment and enhance bone remodeling in OI mice. Thus, this study will be helpful in developing future autologous immunotherapy-based treatment modalities for OI.

15.
Curr Biol ; 32(5): 1010-1025.e9, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35114097

RESUMO

Sensorimotor transformations are mediated by premotor brain networks where individual neurons represent sensory, cognitive, and movement-related information. Such multiplexing poses a conundrum-how does a decoder know precisely when to initiate a movement if its inputs are active at times when a movement is not desired (e.g., in response to sensory stimulation)? Here, we propose a novel hypothesis: movement is triggered not only by an increase in firing rate but, critically, also by a reliable temporal pattern in the population response. Laminar recordings in the macaque superior colliculus (SC), a midbrain hub of orienting control, and pseudo-population analyses in SC and cortical frontal eye fields (FEFs) corroborated this hypothesis. Specifically, using a measure that captures the fidelity of the population code-here called temporal stability-we show that the temporal structure fluctuates during the visual response but becomes increasingly stable during the movement command. Importantly, we used spatiotemporally patterned microstimulation to causally test the contribution of population temporal stability in gating movement initiation and found that stable stimulation patterns were more likely to evoke a movement. Finally, a spiking neuron model was able to discriminate between stable and unstable input patterns, providing a putative biophysical mechanism for decoding temporal structure. These findings offer new insights into the long-standing debate on motor preparation and generation by situating the movement gating signal in temporal features of activity in shared neural substrates, and they highlight the importance of short-term population history in neuronal communication and behavior.


Assuntos
Neurônios , Colículos Superiores , Neurônios/fisiologia , Movimentos Sacádicos , Colículos Superiores/fisiologia
16.
Neuron ; 110(7): 1139-1155.e6, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35120626

RESUMO

The biophysical properties of existing optogenetic tools constrain the scale, speed, and fidelity of precise optogenetic control. Here, we use structure-guided mutagenesis to engineer opsins that exhibit very high potency while retaining fast kinetics. These new opsins enable large-scale, temporally and spatially precise control of population neural activity. We extensively benchmark these new opsins against existing optogenetic tools and provide a detailed biophysical characterization of a diverse family of opsins under two-photon illumination. This establishes a resource for matching the optimal opsin to the goals and constraints of patterned optogenetics experiments. Finally, by combining these new opsins with optimized procedures for holographic photostimulation, we demonstrate the simultaneous coactivation of several hundred spatially defined neurons with a single hologram and nearly double that number by temporally interleaving holograms at fast rates. These newly engineered opsins substantially extend the capabilities of patterned illumination optogenetic paradigms for addressing neural circuits and behavior.


Assuntos
Rede Nervosa , Opsinas , Optogenética , Holografia/métodos , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Opsinas/química , Opsinas/genética , Optogenética/métodos
17.
Artigo em Inglês | MEDLINE | ID: mdl-34723801

RESUMO

Our previous methodology in local sound speed estimation utilized time delays measured by the cross correlation of delayed full-synthetic aperture channel data to estimate the average speed of sound. However, focal distortions in this methodology lead to biased estimates of the average speed of sound, which, in turn, leads to biased estimates of the local speed of sound. Here, we demonstrate the bias in the previous methodology and introduce a coherence-based average sound speed estimator that eliminates this bias and is computationally much cheaper in practice. Because this coherence-based approach estimates the average sound speed in the medium over an equally spaced grid in depth rather than time, we derive a refined model that relates the local and average speeds of sound as a function of depth in layered media. A fast, closed-form inversion of this model yields highly accurate local sound speed estimates. The root-mean-square (rms) error of local sound speed reconstruction in simulations of two-layer media is 4.6 and 2.5 m/s at 4 and 8 MHz, respectively. This work examines the impact of frequency, f -number, aberration, and reverberation on sound speed estimation. Phantom and in vivo experiments in rats further validate the coherence-based sound speed estimator.


Assuntos
Som , Animais , Frequência Cardíaca , Imagens de Fantasmas , Ratos , Ultrassonografia/métodos
18.
Contemp Clin Dent ; 13(4): 356-362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36686999

RESUMO

Objectives: To compare and evaluate the bond durability, surface morphology, and remineralization of the adhesive layer with newer adhesive systems modified with novel bioactive nanoparticles. Methodology: Bonding agents evaluated in this study include (a) Conventional dentin bonding agent (CN-DBA) (b) Nanohydroxyapatite (nanoHAP) incorporated dentin bonding agent (NH DBA); (c) Silica doped nanohydroxyapatite (Si nanoHAP) incorporated dentin bonding agent (Si NH DBA). A total of 104 human dentin discs (5 mm × 5 mm × 2 mm) were sectioned. Elemental analysis (Ca/P ratio) and surface morphology of the adhesive layer with different dentin adhesives were evaluated under scanning electron microscopy with energy-dispersive X-ray analysis after speculated storage time of 1 day and 6 months. Microshear bond strength of adhesive restorations with different dentin adhesives was evaluated under universal testing machine and fractographic analysis under scanning electron microscope after speculated storage time of 1 day and 6 months. The results were analyzed using analysis of variance and post hoc analysis. Results: Si-NH-DBA showed highest mean microshear bond strength for both 1 day and 6 months, which was significantly higher compared to conventional nanofilled dentin bonding agent (CN-DBA) and NH-DBA. Si-NH-DBA group showed only 10% reduction in bond strength after 6 months, which was less compared to that of other groups. Similarly, Si-NH-DBA showed higher remineralization with stellate-shaped crystals at the adhesive layer after 6 months with hydrolytic resistant hybrid layer, compared to CN-DBA and NH-DBA. Conclusion: Silica-doped nanohydroxyapatite proved its efficiency on bond stability, remineralization, and hydrolytic resistance when incorporated into dentin bonding agents because of its bioactivity and carbonate-containing apatite-forming ability.

19.
Adv Funct Mater ; 31(41)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34899115

RESUMO

Camouflaged cell-membrane-based nanoparticles have been gaining increasing attention owing to their improved biocompatibility and immunomodulatory properties. Using nanoparticles prepared from the membranes of specific cell types, or fusions derived from different cells membranes, can improve their functional performance in several aspects. Here, we used cell membranes extracted from breast cancer cells and platelets to fabricate a hybrid-membrane vesicle fusion (cancer cell-platelet-fusion-membrane vesicle, CPMV) in which we loaded therapeutic microRNAs (miRNAs) for the treatment of triple-negative breast cancer (TNBC). We used a clinically scalable microfluidic platform for the fusion of cell membranes. The reconstitution process during synthesis allows for efficient loading of miRNAs into CPMVs. We systematically optimized the conditions for preparation of miRNA-loaded CPMVs and demonstrated their property of homing to source cells using in vitro experiments, and by therapeutic evaluation in vivo. In vitro, the CPMVs exhibited significant recognition of their source cells and avoided engulfment by macrophages. After systemic delivery in mice, the CPMVs showed a prolonged circulation time and site-specific accumulation at implanted TNBC-xenografts. The delivered antimiRNAs sensitized TNBCs to doxorubicin, resulting in an improved therapeutic response and survival rate. This strategy has considerable potential for clinical translation to improve personalized therapy for breast cancer and other malignancies.

20.
Transfus Apher Sci ; 60(6): 103283, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34625349

RESUMO

INTRODUCTION: Increasing demand for platelet transfusion implies the need to recruit greater numbers of donors. We planned this study to evaluate donor safety issues with regards to changes in hematological values after plateletpheresis to improve donor safety and satisfaction. MATERIALS & METHODS: The study was conducted on 1000 healthy plateletpheresis donors over a period of 24 months. Pre- and post-apheresis hematological parameters of donors were analyzed. Recovery of platelet was also observed in plateletpheresis donor who returned to after 48 h. RESULT: We observed that the Platelet counts decreased significantly in the plateletpheresis donors (p=<0.001) after each procedure and there was a non-significant decline in Hb (p = 0.34), Hct (p = 0.44) and RBCs (p = 0.08). The hematological changes were within the normal limits with no clinical evidence of anemia or thrombocytopenia. Recovery of platelets in plateletpheresis donors after 48 h was observed in 30 donors (0.03 %). CONCLUSION: A significant immediate post procedure decrease in platelet count was observed in our study but the recovery of platelets was adequate suggesting next platelet collection from the donor can be safely done after a period of 48 h.


Assuntos
Transfusão de Plaquetas/métodos , Plaquetoferese/métodos , Adulto , Doadores de Sangue , Humanos , Índia , Masculino , Estudos Prospectivos
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