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Nevin Manimala Statistics

Tunable Crosslinking, Reversible Phase Transition, and 3D Printing of Hyaluronic Acid Hydrogels via Dynamic Coordination of Innate Carboxyl Groups and Metallic Ions

ACS Appl Bio Mater. 2021 Mar 15;4(3):2408-2428. doi: 10.1021/acsabm.0c01300. Epub 2021 Feb 15.

ABSTRACT

This article reports tunable crosslinking, reversible phase transition, and three-dimensional printing (3DP) of hyaluronic acid (HyA) hydrogels via dynamic coordination of Fe3+ ions with their innate carboxyl groups for the first time. The concentrations of Fe3+ and H+ ions and the reaction time determine the tunable ratios of mono-, bi-, and tridentate coordination, leading to the low-to-high crosslinking densities and reversible solid-liquid phase transition of HyA hydrogels. At the monodentate-dominant coordination, the liquid hydrogels have low crosslinking densities (HyA_L). At the mixed coordination of mono-, bi-, and tridentate bonding, the solid hydrogels have medium crosslinking densities (HyA_M). At the tridentate-dominant coordination, the solid hydrogels have high crosslinking densities (HyA_H). The reversible solid-liquid phase transitions among HyA_L, HyA_M, and HyA_H were achieved via controlling the concentrations of Fe3+ and H+ ions and reaction time. When the crosslinking densities are between HyA_L and HyA_M, the hydrogels become 3D printable (HyA_P). HyA_P hydrogels were 3D-printed successfully using cold-stage or direct writing methods, and the 3D constructs achieved better structural stability using the latter method. In the direct exposure culture with bone marrow-derived mesenchymal stem cells, the 3D-printed HyA_H (HyA_H_3D) and HyA_H hydrogels showed higher average cell adhesion densities than the HyA_M, HyA_P, and HyA_L hydrogel groups under both direct and indirect contact conditions. For all hydrogel groups, cell adhesion densities under direct contact conditions were statistically lower than the same groups under indirect contact conditions. In this article, we elucidated the mechanisms of dynamic coordination and the relationships among the key parameters in controlling the tunable crosslinking, reversible phase transition, and 3DP of HyA hydrogels without blending with other polymers or adding functional groups. This approach can be potentially adapted to crosslink and 3D print other polymeric hydrogels with carboxyl groups, which is promising for a wide range of applications.

PMID:35014361 | DOI:10.1021/acsabm.0c01300

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Nevin Manimala Statistics

Amphiphilic Graft Copolymers Capable of Mixed-Mode Interaction as Alternative Nonviral Transfection Agents

ACS Appl Bio Mater. 2021 Feb 15;4(2):1268-1282. doi: 10.1021/acsabm.0c01123. Epub 2021 Jan 12.

ABSTRACT

Nonviral gene delivery vectors are attractive candidates compared to viral ones due to their lower cytotoxicity and immunogenicity. However, their efficacy still requires improvement. Major challenges are the effective complexation and protection of the DNA cargo and the intracellular dissociation of the polyplexes at the site of action. It is commonly accepted that polymer architecture and chemistry influence polyplex characteristics and have an impact on the transfection mechanism. We developed a library of biocompatible copolymers based on methoxy poly(ethylene glycol) and a hydrophobic block of poly(ε-caprolactone-co-propargyl carbonate) grafted with a predetermined number of poly(2-(dimethylamino)ethyl methacrylate) segments. Such copolymers could efficiently deliver their cargo even in the presence of serum proteins and to various “difficult to transfect” cells, thereby outperforming the current gold standard 25 kDa linear poly(ethylenimine). Statistical correlation analysis shows that an optimization of the transfection in the case of copolymers combining several interactive functions benefits from treatment as a multiparameter problem.

PMID:35014479 | DOI:10.1021/acsabm.0c01123

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Nevin Manimala Statistics

Synthesis of a High Affinity Complementary Peptide-Polymer Nanoparticle (NP) Pair Using Phage Display

ACS Appl Bio Mater. 2021 Mar 15;4(3):2704-2712. doi: 10.1021/acsabm.0c01631. Epub 2021 Feb 18.

ABSTRACT

Peptide-polymer complementary pairs can provide useful tools for isolating, organizing, and separating biomacromolecules. We describe a procedure for selecting a high affinity complementary peptide-polymer nanoparticle (NP) pair using phage display. A hydrogel copolymer nanoparticle containing a statistical distribution of negatively charged and hydrophobic groups was used to select a peptide sequence from a phage displayed library of >1010 peptides. The NP has low nanomolar affinity for the selected cyclic peptide and exhibited low affinity for a panel of diverse proteins and peptide variants. Affinity arises from the complementary physiochemical properties of both NP and peptide as well as the specific peptide sequence. Comparison of linear and cyclic variants of the peptide established that peptide structure also contributes to affinity. These findings offer a general method for identifying polymer-peptide complementary pairs. Significantly, precise polymer sequences (proteins) are not a requirement, a low information statistical copolymer can be used to select for a specific peptide sequence with affinity and selectivity comparable to that of an antibody. The data also provides evidence for the physiochemical and structural contributions to binding. The results confirm the utility of abiotic, statistical, synthetic copolymers as selective, high affinity peptide affinity reagents.

PMID:35014309 | DOI:10.1021/acsabm.0c01631

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Nevin Manimala Statistics

Systemic Treatments in Pediatric Psoriasis: A Retrospective Single-Center Study

Arch Iran Med. 2021 Dec 1;24(12):903-909. doi: 10.34172/aim.2021.135.

ABSTRACT

BACKGROUND: Systemic therapies commonly used in adult psoriasis are mostly used only off-label in children and little is known about the efficacy and tolerability of these drugs in this population. In this study, we aimed to evaluate the efficacy and safety of systemic treatments in pediatric patients with psoriasis.

METHODS: Data were obtained retrospectively from the Department of Dermatology, Ondokuz Mayis University, School of Medicine between 2010-2019. Our study consisted of 742 pediatric patients (age ≤18 years) with psoriasis. Demographic data, adverse events of systemic treatments and healing periods were considered.

RESULTS: A total of 195 patients received systemic treatment. The mean age of onset of disease and the initiation of systemic therapy were 9.68±4.62 and 11.33±4.38 years, respectively. Patients received methotrexate (n=52, 26.67%), cyclosporine (n=18, 9.24%), acitretin (n=106, 54.35%) and others (biologics and/or one of conventional treatments) (n=19, 9.74%) as systemic therapy. Adverse events occurred in 12 patients (incidence of 6.15%, and its related 95% confidence interval of 2.75%, 9.56%) and nine of them had to discontinue the medication due to those adverse events. Healing periods calculated in the remaining 186 patients were 13.25±5.87, 10.85±5.67, 11.05±7.00, and 9.41±4.16 (mean±SD) weeks for acitretin, methotrexate, cyclosporine, and others, respectively. No statistically significant differences were noted between the treatments regarding the healing periods.

CONCLUSION: All treatments were effective and none of them was superior in terms of the healing period. Systemic treatments used in adults can also be used in pediatric patients with psoriasis with similar efficacy and safety rates as long as routine monitoring is provided.

PMID:35014238 | DOI:10.34172/aim.2021.135

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Nevin Manimala Statistics

Revisiting the annual incidence of Type 1 Diabetes Mellitus in children from the Southeastern Anatolian Region of Turkey: A Regional report

J Clin Res Pediatr Endocrinol. 2022 Jan 11. doi: 10.4274/jcrpe.galenos.2021.2021-10-7. Online ahead of print.

ABSTRACT

OBJECTIVE: Type 1 Diabetes mellitus (T1D) incidence in children has an increasing trend with a variable rate depending on region and ethnicity. Our group had firstly reported T1D incidence in Diyarbakır in the year 2011. The present study aims to evaluate the current incidence rate of pediatric T1D in Diyarbakır, and compare the incidence, clinical and presenting characteristics of the cases with those reported in our first report.

METHODS: Hospital records of the patients under 18 years old and diagnosed with T1D in Diyarbakır city between 1st January 2020 and 31st December 2020 were retrieved, and their medical data was extracted. Demographic population data were obtained from address-based census records of the Turkish Statistical Institution (TSI).

RESULTS: Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female ratio of 1.47. The mean age of diagnosis was 9.5±3.9 (0.8-17.9). According to the data obtained from TSI, the population between the ages of 0-18 was found to be 709803. T1D incidence was calculated as 9.14/105 in the 0-14 age group and 8.03/105 in the 0-18 age group. The cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The frequency of presentation with DKA was 64.9%.

PMID:35014245 | DOI:10.4274/jcrpe.galenos.2021.2021-10-7

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Nevin Manimala Statistics

Implant-supported removable partial dentures compared to conventional dentures: A systematic review and meta-analysis of quality of life, patient satisfaction, and biomechanical complications

Clin Exp Dent Res. 2022 Jan 11. doi: 10.1002/cre2.521. Online ahead of print.

ABSTRACT

OBJECTIVES: The purpose of this systematic review and meta-analysis was to compare implant-supported removable partial dentures (ISRPDs) with distal extension removable partial dentures (DERPDs) in terms of patient-reported outcome measures (PROMs: patients’ quality of life and satisfaction) and to determine mechanical and biological complications associated with ISRPDs.

MATERIAL AND METHODS: An electronic search was performed on four databases to identify studies treating Kennedy class I or II edentulous patients and which compared ISRPDs with DERPDs in terms of PROMS and studies, which evaluated mechanical and biological complications associated ISRPDs. Two authors independently extracted data on quality of life, patient satisfaction, and biomechanical complications from these studies. The risk of bias was assessed for each study, and for PROMs, the authors performed a meta-analysis by using a random-effects model.

RESULTS: Thirteen articles were included based on the selection criteria. The difference in mean scores for quality of life (30.5 ± 1.8; 95% confidence interval [CI], 24.9-36.1) and patient satisfaction (-20.8 ± 0.2; 95% CI, -23.7 to -17.8) between treatments with conventional and implant-supported removable dentures was statistically significant (p < .05). Implant-supported removable dentures improved patients’ overall quality of life and satisfaction. Some mechanical and biological complications, such as clasp adjustment, abutment or implant loosening, marginal bone resorption, and peri-implant mucositis, were noted in ISRPDs during patient follow-up. Studies assessing PROMs were very heterogeneous (I2 = 65%, p = .85; I2 = 75%, p = .88).

CONCLUSIONS: ISRPDs significantly improved quality of life and patient satisfaction. Some mechanical and biological complications have been associated with ISRPDs treatment, requiring regular monitoring of patients to avoid the occurrence of these complications.

PMID:35014207 | DOI:10.1002/cre2.521

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Nevin Manimala Statistics

Detection of candidate genes affecting milk production traits in sheep using whole-genome sequencing analysis

Vet Med Sci. 2022 Jan 11. doi: 10.1002/vms3.731. Online ahead of print.

ABSTRACT

BACKGROUND: Artificial and natural selection for important economic traits and genetic adaptation of the populations to specific environments have led to the changes on the sheep genome. Recent advances in genome sequencing methods have made it possible to use comparative genomics tools to identify genes under selection for traits of economic interest in domestic animals.

OBJECTIVES: In this study, we compared the genomes of Assaf and Awassi sheep breeds with those of the Cambridge, Romanov and British du cher sheep breeds to explore positive selection signatures for milk traits using nucleotide diversity (Pi) and FST statistical methods.

METHODS: Genome sequences from fourteen sheep with a mean sequence depth of 9.32X per sample were analysed, and a total of 23 million single nucleotide polymorphisms (SNPs) were called and applied for this study. Genomic clustering of breeds was identified using ADMIXTURE software. The FST and Pi values for each SNP were computed between population A (Assaf and Awassi) and population B (Cambridge, British du cher, and Romanov).

RESULTS: The results of the PCA grouped two classes for these five dairy sheep breeds. The selection signatures analysis displayed 735 and 515 genes from FST and nucleotide diversity (Pi) statistical methods, respectively. Among all these, 12 genes were shared between the two approaches. The most conspicuous genes were related to milk traits, including ST3GAL1 (the synthesis of oligosacáridos), CSN1S1 (milk protein), CSN2 (milk protein), OSBPL8 (fatty acid traits), SLC35A3 (milk fat and protein percentage), VPS13B (total milk production, fat yield, and protein yield), DPY19L1 (peak yield), CCDC152 (lactation persistency and somatic cell count), NT5DC1 (lactation persistency), P4HTM (test day protein), CYTH4 (FAT Production) and METRNL (somatic cell), U1 (milk traits), U6 (milk traits) and 5S_RRNA (milk traits).

CONCLUSIONS: The findings provide new insight into the genetic basis of sheep milk properties and can play a role in designing sheep breeding programs incorporating genomic information.

PMID:35014209 | DOI:10.1002/vms3.731

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Nevin Manimala Statistics

The status and predictors of self-care among older adults with hypertension in China using the Chinese version of Self-Care of Hypertension Inventory – A cross-sectional study

Nurs Open. 2022 Jan 11. doi: 10.1002/nop2.1165. Online ahead of print.

ABSTRACT

AIM: To investigate the status and predictors of self-care among older adults with hypertension in China by the Chinese version of Self-Care of Hypertension Inventory.

DESIGN: A cross-sectional questionnaire survey.

METHODS: A convenience sampling of 544 older adults with hypertension was surveyed using the Chinese version of Self-Care of Hypertension Inventory. SPSS25.0 software was used for statistical analysis of the data. Generalized liner model univariate analysis and the optimal scaling regression analysis were performed to investigate the predictors of self-care.

RESULTS: The status of self-care was poor with the median and inter-quartile range of total scores of self-care (140.00 ± 67), the scores of self-care maintenance (50 ± 24.76), the scores of self-care management (56.25 ± 29.41) and the scores of self-care confidence (54.79 ± 29.17). Age, family model, primary caregiver, maximum systolic blood pressure, coverage of medical insurance, disease duration, receiving self-care education, education level, economic burden and family history of hypertension were the most powerful predictors of self-care among older adults with hypertension.

PMID:35014206 | DOI:10.1002/nop2.1165

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Nevin Manimala Statistics

Evaluation of risk factors affecting strongylid egg shedding on Hungarian horse farms

Vet Parasitol Reg Stud Reports. 2022 Jan;27:100663. doi: 10.1016/j.vprsr.2021.100663. Epub 2021 Nov 23.

ABSTRACT

In Hungary, equine parasite control is mostly based on traditional approaches involving rotational anthelmintic treatment at regular intervals. Almost no farms utilize fecal egg counts (FECs) on a regular basis to guide deworming treatments. This approach is certainly not sustainable and is the major factor responsible for the current high levels of anthelmintic resistance. The aims of this study were to statistically analyze risk factors associated with strongylid egg count magnitude and prevalence. Fecal samples and horse data (age, pasture history, stocking density, anthelmintic history) were collected from 216 horses on 13 farms in Pest county, Hungary, during the spring of 2020. FECs were determined by Mini-FLOTAC. Logistic regression models were used to evaluate the association of factors with pre-deworming strongylid egg counts. The data were highly overdispersed with approximately 22% (95% Confidence Interval: 17-28%) of the equids shedding 80% of the total strongylid egg output. Strongylid FECs were significantly associated with the age of equids and anthelmintic class used prior to the study. Equids younger than 5 years of age had significantly higher FECs compared to equids in the 5-17-year age range (p = 0.003) and compared to equids aged >17 years (p < 0.001). Equids treated regularly with benzimidazoles had significantly higher FECs than equids with no history of benzimidazole use (p = 0.02). We found that FECs of horses kept at extremely high stocking density (>30 horses/ha) were significantly higher than those kept at low (1-2 horses/ha; p < 0.001) or medium (3-10 horses/ha, p < 0.001) stocking densities. The results demonstrate the value of FEC monitoring and indicate that the efficacy of benzimidazoles should be investigated in Hungary. Moreover our findings demonstrate that reducing stocking density should be considered in cases of high strongylid FECs.

PMID:35012724 | DOI:10.1016/j.vprsr.2021.100663

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Nevin Manimala Statistics

The efficacy and safety of cariprazine in the early and late stage of schizophrenia: a post hoc analysis of three randomized, placebo-controlled trials

CNS Spectr. 2021 Dec 10:1-8. doi: 10.1017/S1092852921000997. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the post hoc analysis was to better understand the efficacy and safety of cariprazine in patients with schizophrenia for less than 5 years (early stage) and for more than 15 years (late stage).

METHODS: Data from three phase II/III randomized, double-blind, placebo-controlled trials with similar design in patients with acute exacerbation of schizophrenia were pooled and patients with early and late stage of schizophrenia were determined. A mixed-effects model for repeated measures approach was applied and least square (LS) mean changes from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total and factor scores were reported. Descriptive statistics were used for safety analyses including treatment emergent adverse events (TEAEs) and discontinuation rates.

RESULTS: Overall, 460 patients were identified as being in the early and 414 in the late stage of schizophrenia. The pooled analysis evaluating mean change from baseline to week 6 in the PANSS total score indicated statistically significant difference between cariprazine and placebo in favor of cariprazine in both the early (LS mean difference [LSMD] -7.5 P < .001) and late stage (LSMD -6.7, P < .01) subpopulation. Early stage patients experienced similar amount of TEAEs (CAR 67.3%, PBO 54.1%) as patients in the late stage (CAR 69.6%, PBO 65.6%).

CONCLUSION: In conclusion, cariprazine, a potent D3-D2 partial agonist has been found to be safe and effective in the treatment of early and late stage schizophrenia.

PMID:35012696 | DOI:10.1017/S1092852921000997