Non-treated Group Research Articles

Treatment of progressive myopia with 0.01% Atropine in children and adolescents: an Italian 4-year follow-up study.

To assess the effectiveness of atropine 0.01% in slowing the progression of myopia in young patients. 2,387 patients with progressive myopia (more than -0.50 spherical diopters ‹D› increased in the last year) were enrolled. They received, every evening, one drop of atropine 0.01% in each eye. Refraction was then measured at baseline (T0) and once a year (T1, T2, T3, T4) for a 4-years follow-up period, and compared with a non-treated control group. A reduction in the myopic progression was observed in the treated group respect to the control one. The average spherical refraction after 4 years increased by 27.06% in the treated group versus 241% of the control one. The difference in spherical increase between the two groups respect to time 0 was appreciable already at the first control, (T1 -T0, -0.21D vs. -1D) and continued to increase for all the 4-years follow-up period (T2-T0, -0.38D vs. -1.91D;T3-T0, -0.52D vs. -2.74D; T4-T0, -0.73D vs. -3.63D, respectively). It was always significant (P<0.01). Compared to the previous year, the average spherical increase was quite stable in the two groups (0.17 vs. 0.87, respectively). No significant tachyphylaxis or adverse effects were observed throughout the examination period. 0.01% atropine was effective in slowing the progression of myopia in the treated group vs. control one. The clinical effect was noticeable already from the first control, and continued for all the observation period. The results of this study agree with those already reported in literature, and confirm the validity of this treatment.

Studying the impact of phycoerythrin on antioxidant and antimicrobial activity of the fresh rainbow trout fillets

Marine cyanobacteria present a significant potential source of new bioactive compounds with vast structural diversity and relevant antimicrobial and antioxidant activities. Phycobiliproteins (PBPs) like phycocyanin (PC), phycoerythrin (PE), and water-soluble cyanobacterial photosynthetic pigments, have exhibited strong pharmacological activities and been used as natural food additives. In this study, phycoerythrin (PE) isolated from a marine strain of cyanobacterium Nostoc sp. Ft salt, was applied for the first time as a natural antimicrobial as well as an antioxidant to increase the shelf life of fresh rainbow trout i.e., (Oncorhynchus mykiss) fillets. Fresh trout fillets were marinated in analytical grade PE (3.9 μg/mL) prepared in citric acid (4 mg/mL), and stored at 4 °C and 8 °C for 21 days. Microbiological analysis, antioxidant activity and organoleptic evaluation of both control and treated fish fillets were then statistically compared. The results demonstrated noticeable (P < 0.05) differences in the microbial counts, antioxidant activity, and organoleptic characteristic values between PE-treated and non-treated groups. In addition, we observed that treating fresh fish fillets with a PE solution leads to a significant increase in shelf life by at least 14 days. Consequently, PE could be an alternative to synthetic chemical additives since it does not contain the potentially dangerous residues of the synthetic chemical additives and is thus healthier to the consumers.

3D Bioprinted Liver-on-a-Chip for Drug Cytotoxicity Screening.

Tissues on a chip are sophisticated three-dimensional (3D) in vitro microphysiological systems designed to replicate human tissue conditions within dynamic physicochemical environments. However, the current fabrication methods for tissue spheroids on a chip require multiple parts and manual processing steps, including the deposition of spheroids onto prefabricated "chips." These challenges also lead to limitations regarding scalability and reproducibility. To overcome these challenges, we employed 3D printing techniques to automate the fabrication process of tissue spheroids on a chip. This allowed the simultaneous high-throughput printing of human liver spheroids and their surrounding polymeric flow chamber "chips" containing inner channels in a single step. The fabricated liver tissue spheroids on a liver-on-a-chip (LOC) were subsequently subjected to dynamic culturing by a peristaltic pump, enabling assessment of cell viability and metabolic activities. The 3D printed liver spheroids within the printed chips demonstrated high cell viability (>80%), increased spheroid size, and consistent adenosine triphosphate (ATP) activity and albumin production for up to 14 days. Furthermore, we conducted a study on the effects of acetaminophen (APAP), a nonsteroidal anti-inflammatory drug, on the LOC. Comparative analysis revealed a substantial decline in cell viability (<40%), diminished ATP activity, and reduced spheroid size after 7 days of culture within the APAP-treated LOC group, compared to the nontreated groups. These results underscore the potential of 3D bioprinted tissue chips as an advanced in vitro model that holds promise for accurately studying in vivo biological processes, including the assessment of tissue response to administered drugs, in a high-throughput manner.

Dual Growth Factor Delivery Using Photo-Cross-Linkable Gelatin Hydrogels for Effectively Reinforced Regeneration of the Rotator Cuff Tendon.

Rotator cuff tears are currently treated with drugs (steroids and nonsteroidal anti-inflammatory drugs) and surgery. However, the damaged rotator cuff requires a considerable amount of time to regenerate, and the regenerated tissue cannot restore the same level of function as that before the damage. Although growth factors can accelerate regeneration, they are difficult to be used alone because of the risk of degradation and the difficulties in ensuring their sustained release. Thus, hydrogels such as gelatin are used, together with growth factors. Gelatin is a biocompatible and biodegradable hydrogel derived from collagen; therefore, it closely resembles the components of native tissues and can retain water and release drugs continuously, while also showing easily tunable mechanical properties by simple modifications. Moreover, gelatin is a natural biopolymer that possesses the ability to form hydrogels of varying compositions, thereby facilitating effective cross-linking. Therefore, gelatin can be considered to be suitable for rotator-to-tendon healing. In this study, we designed photo-cross-linkable gelatin hydrogels to enhance spacing and adhesive effects for rotator cuff repair. We mixed a ruthenium complex (Ru(II)bpy32+) and sodium persulfate into gelatin-based hydrogels and exposed them to blue light to induce gelation. Basic fibroblast growth factor and bone morphogenetic protein-12 were encapsulated in the gelatin hydrogel for localized and sustained release into the wound, thereby enhancing the cell proliferation. The effects of these dual growth factor-loaded hydrogels on cell cytotoxicity and tendon regeneration in rotator cuff tear models were evaluated using mechanical and histological assessments. The findings confirmed that the gelatin hydrogel was biocompatible and that treatment with the dual growth factor-loaded hydrogels in in vivo rotator cuff tear models promoted regeneration and functional restoration in comparison with the findings in the nontreated group. Therefore, growth factor-loaded gelatin-based hydrogels may be suitable for the treatment of rotator cuff tears.

Effect of spermidine on long non-coding RNAs MALAT1 in a rotenone induced-rat model of Parkinson's disease.

Spermidine is a natural biologically active substance that has widespread influences on the body. This study aims to enhance our understanding of the potential effect of spermidine on long non-coding RNA MALAT1 and explore the underlying mechanism in the rotenone-induced rat model of Parkinson's disease. Rats were sacrificed after locomotor behavioral testing. Striatal tissues were used to assess the expression of MALAT1, oxidative stress markers, and autophagy markers. Our study found that treatment with spermidine for 2weeks during the induction of the model significantly improved behavioral assessment, dopamine levels, and attenuated the histopathological changes that occurred in PD in comparison to the non-treated group. Our preliminary study supports the protective effect of spermidine on the activation of autophagy and its antioxidant properties. Part of the antioxidant activity is due to the inhibition of MALAT1. However, MALAT1 does not correlate with the spermidine-induced autophagy pathway.

The effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years: A national cohort study in Denmark.

Because long-term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well-described, we studied effectiveness over 18 years in Denmark. A register-based cohort study using data on filled prescriptions, 1995-2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non-treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti-allergic nasal inhaler during the pollen season in the treated versus non-treated group by years since baseline. Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0-5 years after baseline was reduced when compared with 15,520 non-treated AR individuals (0-2 years, OR 0.84 (0.81-0.88); 3-5 years, OR 0.88 (0.84-0.92)), but was close to unity or higher thereafter (6-9 years, OR 1.03 (0.97-1.08); 10-18 years, OR 1.18 (1.11-1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0-2 years, OR 0.76 (0.72-0.79); 3-5 years OR 0.86 (0.81-0.93); 6-9 years, OR 0.94 (0.87-1.02); 10-18 years, OR 0.94 (0.86-1.04)) as opposed to no such use. Patients treated with pollen AIT in routine care to a higher degree stopped using anti-allergic nasal inhaler 0-5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR.

Efficacy of the marine red alga Laurencia papillosa extract on alloxan stimulated hyperglycemic activity in male wistar albino rats

PurposeDiabetes mellitus, a main health concern worldwide, is one of the most common metabolic disorders characterized by insulin secretion dysfunction. Materials and methodsIn this work, dietary fibers of the ethanolic extract of Laurencia papillosa were detected at 0.1 and 0.2 g/kg body weight using gas chromatography-mass spectrometry (GC-MS). The extract was given orally once daily to male diabetic rats induced with alloxan for two weeks. The blood cholesterol levels, complete blood count, liver function, kidney function, and antioxidant enzymes were analyzed. The molecular docking was operated using Auto Dock Vina. ResultsTreatment with extracts of L. papillosa (0.1–0.2 g/kg) induced a decrease in pre-prandial and post-prandial glucose levels. 0.1 g/kg pre-prandial extract had the highest activity to reduction glucose level (48.670 ± 0.57 mg/dL). Moreover, the complete blood count, kidney function, and liver function differed slightly in the treated mice group compared to the non-treated diabetic group. Docking analyses demonstrated that most ethanolic compounds found within L. papillosa extract have minimum docking scores and high binding affinity against human pancreatic alpha-amylase (PDB: 4W93), insulin receptor (PDB:1IR3), and SIRT-6 (PDB: 3k35) ConclusionResults further suggested that the concentration of 0.1 g/kg of L. papillosa extract was more effective than 0.2 g/kg in reducing glucose levels. Our study induced that in vivo and in silico results indicated that L. papillosa extract has been a viable natural bioactive source and might be a great potential source for future antidiabetic medicine.

Ameliorative effect of apple cider vinegar and p-coumaric acid combination in Ex ovo antimicrobial and in vivo wound healing models

BackgroundApple cider vinegar (ACV) is most commonly used in sweet and sour Chinese cuisine. This study aimed to overcome the side effects of raw ACV, by increasing the concentration of p-Coumaric acid (p-CA), a polyphenolic component of ACV. The combination (diluted ACV with p-CA) has also been compared with individual raw ACV and p-CA to confirm if the overall dosage of the ACV can be reduced to avoid side effects and if the combination therapy had any better effect than the individual component itself. ObjectiveTo evaluate and compare antioxidant, antimicrobial, and wound healing effects of ACV and p-CA combination with individual components ACV and p-CA. MethodsThe antimicrobial properties of the samples were assessed by determining the Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the broth microdilution method, and zone of inhibition (ZOI) and an ex ovo study was also done to evaluate the antimicrobial effect of the samples in live embryo. For the evaluation of the test samples excision wound was created in Swiss male albino mice weighing 25–30 g of either sex to estimate parameters like wound contraction rate, WBC and platelet count, SOD and GSH levels. Histopathological analysis of the skin was also done. ResultIn DPPH and ABTS antioxidant assays, the combined sample (ACV + p-CA) had lower IC50. The combination therapy also showed the best antimicrobial potential against P. aeruginosa and B. subtilis. In this context, ex-ovo antimicrobial study results showed that diluted ACV + p-CA treated live embryo samples had the least bacterial growth after 48 h, in comparison with non-treatment group as well as individually ACV and p-CA treated samples. In vivo study depicted that the highest dose of the combination test sample had the best wound contraction rate and antioxidant marker enzymes elevation compared to diseased control proving the potency to restore the wound healing progression. ConclusionACV and p-CA combination can be used with daily intake as this combination can prevent microbial contamination and oxidative stress additionally can repair wounds more safely than raw ACV.

Improving Prenatal Diagnosis Precision for Congenital Clubfoot by Using Three-Dimensional Ultrasonography.

Prenatal diagnosis of clubfoot traditionally relied on two-dimensional ultrasonography. To enhance diagnosis and predict postnatal outcomes, we examined the parameters that differentiate pathological clubfoot using three-dimensional ultrasonography. In our retrospective study, we examined the findings of prenatal ultrasound and the postnatal outcomes of pregnancies with suspected congenital clubfoot between 2018 and 2021. Based on the three-dimensional perspective, we measured the angles of varus, equinus, calcaneopedal block, and forefoot adduction and compared the sonographic variables between the postnatal treated and non-treated groups. We evaluated 31 pregnancies (47 feet) with suspected clubfoot using three-dimensional ultrasonography. After delivery, a total of 37 feet (78.7%) underwent treatment involving serial casting only or additional Achilles tenotomy. The treated group showed significantly greater hindfoot varus deviation (60.5° vs. 46.6°, p = 0.026) and calcaneopedal block deviation (65.6° vs. 26.6°, p < 0.05) compared to the non-treated group. The calcaneopedal block had an area under the curve of 0.98 with a diagnostic threshold of 46.2 degrees (sensitivity of 97%, specificity of 90%, positive predictive value of 97%, and negative predictive value of 90%). During prenatal evaluation of clubfoot using three-dimensional ultrasonography, the calcaneopedal block deviation has the potential to predict postnatal treatment.

Evaluation of Non-invasive Fat Reduction Using a Resistive Electric Transfer-based Radiofrequency Device With Multi-channel Handpieces.

Various devices for non-invasive body shape correction are being developed along with the growth of the beauty industry. Radiofrequency (RF) can selectively reduce subcutaneous fat without causing skin damage. The efficacy of the procedure can be improved by applying RF to a large area simultaneously with multiple handpieces. This study evaluated the safety and efficacy of a new RF device with multi-channel handpieces. In ex vivo experiments, the RF device was used to treat porcine tissue comprising the skin, subcutaneous, and muscle layers. The device's safety was evaluated by temperature measurements of porcine tissue and histological analysis. In in vivo experiments, the dorsal skin of pigs was treated with the RF device. The safety and efficacy of the device were evaluated by measuring the skin temperature, subcutaneous fat layer thickness, and conducting histological analysis. The skin temperature did not exceed the set temperature during treatment, and skin damage was not observed in histologic analysis in both ex vivo and in vivo experiments. In in vivo experiments, the subcutaneous fat layer thickness and subcutaneous lipocyte size were decreased after treatment. In addition, the fibrous tissue between subcutaneous lipocytes was increased in the RF treatment group compared with the non-treatment group. The RF device used in this study effectively reduced the size of subcutaneous lipocytes and increased fibrous tissue without skin damage. Therefore, the safe and effective use of this device for non-invasive fat reduction may be possible in clinical settings.

Enhancement of the efficacy of Tylvalosin by administration with Eucalyptus oil or Bromhexine against Mycoplasma gallisepticum-infected broiler chickens

Abstract Tylvalosin tartrate is a macrolide antibiotic that has antibacterial activity against Gram-positive, some Gram-negative organisms, and mycoplasma. It acts by inhibiting protein synthesis in bacterial cells. Mycoplasma gallisepticum causes chronic respiratory disease in poultry, especially in the presence of management stresses and other respiratory pathogens. The disease is characterized by coryza, conjunctivitis, sneezing, and sinusitis, particularly in turkeys and birds. It can result in loss of production downgrading of meat-type birds, and loss of egg production. In the current study, the efficacy of tylvalosin on performance parameters, hematological and biochemical profile alone, and in combination with eucalyptus oil and bromhexine were studied. A total of 56-day adult chickens were used in the experiment and infection occurred by Mycoplasma gallisepticum. The birds were classified into seven groups and treated as follows; non-infected non-treated group (control negative), infected non-treated group (control positive), group infected and treated by tylvalosin alone, group infected and treated by eucalyptus oil, group infected and treated by bromhexine, group infected and treated by tylvalosin plus eucalyptus oil, and group infected and treated by tylvalosin plus bromhexine. Clinical symptoms, bacterial re-isolation, mortality rate, and hematobiochemical and histopathological parameters were investigated. The results showed a significant decrease in mortality &amp; improved growth performance (increased weight gain and feed utilization efficiency) in combined treated groups compared to tylvalosin group as well as improvement in hematobiochemical and histopathological parameters of combined treated groups. Furthermore, the combination of tylvalosin and eucalyptus oil or bromhexine was more potent in the treatment of Mycoplasmosis in chickens than each treatment alone and alleviated or partially reduced the severity of chronic respiratory disease induced by Mycoplasma gallisepticum in broiler chickens. Finally, this protective effect could improve the use of antibiotics in poultry farms as well as reduce the problem of antibiotic residues and bacterial resistance to antibiotics.

Media framing and trust: A randomized survey experiment on attitudes towards the unvaccinated during the COVID-19 pandemic

This research examines the influence of news media and trust in institutions on how vaccinated individuals in Finland perceived the unvaccinated during the COVID-19 pandemic. The study employed a randomized survey experiment involving 455 participants and incorporated episodic and thematic news framings on vaccine side effects alongside a non-treatment control group. Episodic framing, which presented personal stories, was found to significantly reduce the inclination to impose additional restrictions on the unvaccinated and lessen the perception of them as an outgroup. The converse effect was shown in thematic framing, which focused on statistics and expert opinions. The study also underscored the pivotal role of trust in institutions: lower trust increases the influence of episodic framing, while strong political trust can mitigate the effects of news framing. This investigation provides vital insights into the interplay between media framing and trust levels in shaping public attitudes towards health risks and non-adherence during a health emergency.

A unique combination of natural fatty acids from Hermetia illucens fly larvae fat effectively combats virulence factors and biofilms of MDR hypervirulent mucoviscus Klebsiella pneumoniae strains by increasing Lewis acid-base/van der Waals interactions in bacterial wall membranes.

Hypervirulent Klebsiella pneumoniae (hvKp) and carbapenem-resistant K. pneumoniae (CR-Kp) are rapidly emerging as opportunistic pathogens that have a global impact leading to a significant increase in mortality rates among clinical patients. Anti-virulence strategies that target bacterial behavior, such as adhesion and biofilm formation, have been proposed as alternatives to biocidal antibiotic treatments to reduce the rapid emergence of bacterial resistance. The main objective of this study was to examine the efficacy of fatty acid-enriched extract (AWME3) derived from the fat of Black Soldier Fly larvae (Hermetia illucens) in fighting against biofilms of multi-drug resistant (MDR) and highly virulent Klebsiella pneumoniae (hvKp) pathogens. Additionally, the study also aimed to investigate the potential mechanisms underlying this effect. Crystal violet (CV) and ethidium bromide (EtBr) assays show how AWME3 affects the formation of mixed and mature biofilms by the KP ATCC BAA-2473, KPi1627, and KPM9 strains. AWME3 has shown exceptional efficacy in combating the hypermucoviscosity (HMV) virulent factors of KPi1627 and KPM9 strains when tested using the string assay. The rudimentary motility of MDR KPM9 and KP ATCC BAA-2473 strains was detected through swimming, swarming, and twitching assays. The cell wall membrane disturbances induced by AWME3 were detected by light and scanning electron microscopy and further validated by an increase in the bacterial cell wall permeability and Lewis acid-base/van der Waals characteristics of K. pneumoniae strains tested by MATS (microbial adhesion to solvents) method. After being exposed to 0.5 MIC (0.125 mg/ml) of AWME3, a significant reduction in the rudimentary motility of MDR KPM9 and KP ATCC BAA-2473 strains, whereas the treated bacterial strains exhibited motility between 4.23 ± 0.25 and 4.47 ± 0.25 mm, while the non-treated control groups showed significantly higher motility ranging from 8.5 ± 0.5 to 10.5 ± 0.5 mm. In conclusion, this study demonstrates the exceptional capability of the natural AWME3 extract enriched with a unique combination of fatty acids to effectively eliminate the biofilms formed by the highly drug-resistant and highly virulent K. pneumoniae (hvKp) pathogens. Our results highlight the opportunity to control and minimize the rapid emergence of bacterial resistance through the treatment using AWME3 of biofilm-associated infections caused by hvKp and CRKp pathogens.

Effectiveness and Tolerability of Dual Therapy with Dolutegravir Plus Darunavir/cobicistat in Treatment-Experienced Patients with HIV: A 144-Week Follow-Up.

A dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG+DRV/c) is a promising alternative for patients with human immunodeficiency virus (HIV) with resistance or intolerance to nucleoside reverse transcriptase inhibitors, especially those with a history of treatment failure. We included all treatment-experienced patients with HIV who switched to the DTG+DRV/c regimen at a tertiary university hospital. We assessed the regimen's effectiveness, safety, and tolerability through serial laboratory data and clinical findings. The primary endpoint was the proportion of patients with plasma HIV-RNA levels <50 copies/mL at week 144 post-switch. The secondary endpoints were safety and tolerability assessments. Our retrospective analysis involved 40 patients. The leading reasons for switching to DTG+DRV/c were treatment failure in 17 patients (42.5%), simplification after multiple previous regimens in 15 (37.5%), and adverse drug reactions in 8 (20.0%). Among the 17 patients in the treatment failure group, we observed enhanced viral suppression and improved CD4+ T-cell counts after initiating the dual regimen. In the non-treatment failure group (23 patients), viral suppression and CD4+ T-cell levels were consistently maintained. No significant alterations in renal function, liver function, glucose levels, or lipid profiles were observed post-switch. High tolerability was observed, with 34/40 patients (85.0%) responding well to the regimen. However, six patients discontinued treatment before reaching the 144-week mark. Our findings confirm that DTG+DRV/c is an effective and well-tolerated switch therapy regimen for treatment-experienced patients with HIV, with sustained benefits observed for up to 144 weeks of follow-up. This regimen showed adaptability across different patient groups and demonstrated virological and immunological improvements, particularly in patients with a history of treatment failure.

Treatment-seeking behavior and cardiovascular morbidity among men with anabolic-androgenic steroid use: Across-sectional study.

To determine associations between anabolic-androgenic steroid (AAS) use-related morbidity including cardiovascular disease (CVD) and engagement to health services. In this cross-sectional study, 90 males with at least 12 months cumulative current or former use of AAS were included. The participants were divided into a treatment-seeking group (TSG) and a non-treatment seeking group (non-TSG) based on their responses to a self-report web questionnaire. All participants were screened for symptoms that could be indicative of CVD through a clinical interview, and examined with blood samples, blood pressure measurements and transthoracic echocardiography. In the total sample (n = 90), mean age was 39 ± 11 years with cumulative AAS use of 12 ± 9 years. Among men in the TSG with current use there were higher prevalence of dyspnoea (50% vs 7%) and reduced left ventricular ejection fraction (LVEF) in conjunction with left ventricular hypertrophy (LVH) (36 vs. 9%) and/or high blood pressure (55% vs. 19%) compared to men in the non-TSG. Among men with current AAS use and established LVEF <50% (n = 25) or LVH (n = 21), 44% (11) and 43% (9) respectively, had never engaged health services due to AAS-related adverse effects. Deviant liver- and kidney parameters were frequently observed in the total sample but without between-group differences. Treatment-seeking behavior among current AAS users may be associated with increased levels of dyspnoea and established CVD. Despite objective signs of severe CVD among a substantial amount of study participants, it is of great concern that the majority had never sought treatment for AAS-related concerns.

The influence of polyimide MP-1™ wear particles on a rodent closed fracture healing model.

Joint replacements provide pain free movement for the injured or our aging population. Current prothesis mainly consist of hard metal on metal, or ceramic femoral head on ultra-high-molecular weight polyethylene (UHMWPE). In this study, a rodent fracture model was used to test the influence of wear debris from a high-performance polymer (polyimide MP-1™). Saline, MP-1™ Low Dose in Saline (1%), or MP-1 High Dose (2%) in Saline was injected directly into a standard closed unilateral femoral fracture in 12-week old Sprague Dawley rats (n = 25) for 1, 3 and 6 weeks. Endpoints included radiography, micro-computed tomography, mechanical testing and paraffin histology. No adverse effects from the wear particles were observed from the current study based on radiology, mechanical or histological data. Although the particles were present, histological analysis revealed a progression in healing between the Polyimide treated groups and the non-treated saline control groups over the duration of 1, 3, and 6 weeks, with no inhibition from the particles. The MP-1™ wear debris generated are larger than 1 µm thus are not able to be engulfed by macrophages and cause osteolysis. This family of polymers (polyimides) may be an ideal material to consider for articulating joints and other implants in the human body.

Learning Non-monotone Optimal Individualized Treatment Regimes

We propose a new modeling and estimation approach to select the optimal treatment regime from different options through constructing a robust estimating equation. The method is protected against misspecification of the propensity score model, the outcome regression model for the non-treated group, or the potential non-monotonic treatment difference model. Our method also allows residual errors to depend on covariates. A single index structure is incorporated to facilitate the nonparametric estimation of the treatment difference. We then identify the optimal treatment through maximizing the value function. Theoretical properties of the treatment assignment strategy are established. We illustrate the performance and effectiveness of our proposed estimators through extensive simulation studies and a real dataset on the effect of maternal smoking on baby birth weight.

Allium tuberosum-derived nanovesicles with anti-inflammatory properties prevent DSS-induced colitis and modify the gut microbiome.

Edible plant-derived nanovesicles (ePDNs) have shown potential as a non-pharmacological option for inflammatory bowel disease (IBD) by maintaining gut health and showing anti-inflammatory effects. However, the effects of Allium tuberosum-derived nanovesicles (ADNs) on colitis have not been studied to date. Here, we extracted exosome-like nanovesicles from Allium tuberosum and investigated whether they have an anti-inflammatory effect in RAW 264.7 cells and colitis mice. The results showed that ADNs reduced the elevated levels of inflammatory factors such as IL-1β, IL-6, TNF-α, and NF-κB pathway-related proteins as a consequence of lipopolysaccharide (LPS) stimulation in RAW 264.7 cells. Furthermore, our mouse experiments demonstrated that ADNs could ameliorate dextran sulfate sodium (DSS)-induced colitis symptoms (e.g., increased disease activity index score, intestinal permeability, and histological appearance). Additionally, ADNs counteracted DSS-induced colitis by downregulating the expression of serum amyloid A (SAA), IL-1β, IL-6, and TNF-α and increasing the expression of tight junction proteins (ZO-1 and occludin) and the anti-inflammatory cytokine IL-10. 16S rRNA gene sequencing showed that ADN intervention restored the gut microbial composition, which was similar to that of the DSS non-treated group, by decreasing the ratio of Firmicutes to Bacteroidetes and the relative abundance of Proteobacteria. Furthermore, ADNs induced acetic acid production along with an increase in the abundance of Lactobacillus. Overall, our findings suggest that ADN supplementation has a crucial role in maintaining gut health and is a novel preventive therapy for IBD.

Novel treatment of intracerebral hemorrhage with mechanical tissue resuscitation.

The previous laboratory and clinical experience of the authors had demonstrated that application of controlled subatmospheric pressure directly to injured soft tissue can result in increased survival of compromised tissues. Mechanical tissue resuscitation (MTR) is a new concept evolving from these discoveries. The authors' recent studies have demonstrated that traumatic brain injury tissue can also be salvaged. The aim of this study was to examine the effects of MTR application to injuries from intracerebral hemorrhages (ICHs) in a swine model. The ICHs in swine were simulated by infusion of autologous artery blood into the right frontal lobe. A specially designed silicone manifold device was introduced directly into the hematoma. Continuous negative pressure at -50 mm Hg was applied through this device. T2- and T2*-weighted MRI, histological H&E staining, and immunostaining were examined. After 1 week of treatment, MTR significantly decreased gross hematoma volume by more than 60%, from 472.62 ± 230.19 mm3 in the nontreated group to 171.25 ± 75.38 mm3 in the MTR-treated group (p < 0.05). Total hypointense volumes measured on T2*-weighted MR images decreased from 791.99 ± 360.47 mm3 in the nontreated group to 371.16 ± 105.75 mm3 in the MTR-treated group (p < 0.05). The hyperintense area on the T2-weighted MR image decreased significantly from 2656.23 ± 426.26 mm3 in the nontreated group to 1816.66 ± 525.26 mm3 in the MTR-treated group (p < 0.05). When ICHs were treated with MTR for 2 weeks, the gross hematomas were reduced by 94%, from 112.23 ± 66.21 mm3 in the nontreated group to 6.12 ± 10.99 mm3 in the MTR-treated group (p = 0.003). MTR significantly decreased the total necrotic tissue volume in H&E staining from 120.42 ± 48.35 mm3 in the nontreated group to 60.94 ± 38.99 mm3 in the MTR-treated group (p < 0.05). The total hypointense volumes on T2*-weighted MR images were significantly reduced, from 385.54 ± 93.85 mm3 in the nontreated group to 220.54 ± 104.28 mm3 in the MTR-treated group (p < 0.05), while their mean T2 hyperintense volume decreased significantly from 2192.83 ± 728.27 mm3 in the nontreated group to 1366.97 ± 463.36 mm3 in the MTR-treated group (p < 0.05). Histology revealed that the capillary diameter in the reactive tissue rim adjacent to the hematoma increased in both the 1- and 2-week MTR-treated groups. Both von Willebrand factor and CD31 signals were detectable in endothelial cells within the hematoma cavity of both MTR-treated groups. This study demonstrates that local continuous application of controlled subatmospheric pressure to an ICH can safely remove more than half of a clot in 1 week and more than 90% in 2 weeks.

Effects of prebiotic (lactoferrin) and diclazuril on broiler chickens experimentally infected with Eimeria tenella.

Avian coccidiosis presents a significant challenge to the poultry industry in Egypt, highlighting the urgent need for validating new drug targets offering promising prospects for the development of advanced anticoccidials. Although numerous reports highlight the activity of lactoferrin (LF) against various microorganisms, its potential against Eimeria has not been explored. The present study evaluated the potential anticoccidial effect of LF and diclazuril in broiler chickens experimentally infected with Eimeria tenella. A total of 100 one-day-old broiler chicks were divided into five equal groups (20 each) as follows: Group 1 (G1) served as the normal healthy control group, Group 2 (G2) consisted of chickens infected with 1 × 105 sporulated E. tenella oocysts at 14 days of age, Group 3 (G3) comprised infected chickens treated with diclazuril (0.5 mL/L in drinking water) for 3 days successively, Group 4 (G4) included infected chickens treated with LF (at a dose of 250 mg/kg of diet) from one day of age until the end of the study, and Group 5 (G5) comprised infected chickens treated with both LF and diclazuril. The positive control group (G2) experienced significant reductions in body weight (BW), BW gain, serum glucose, lipase, amylase, total antioxidant capacity, several hematological indices, and total proteins, along with alterations in various antioxidant enzymes. Conversely, serum levels of aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatases (ALP), urea, creatinine, nitric oxide, mean corpuscular volume (MCV), White blood cells (WBCs), heterophils, alpha 2, beta 1, and liver contents of malondialdehyde were elevated in this group. Moreover, higher oocyst counts and lesion scores, along with histopathological alterations, were observed in G2. Remarkably, treatment with diclazuril and/or LF demonstrated potent antioxidant and anticoccidial effects, resulting in reduced shedding of oocysts, lesion scores, and lymphocytic infiltrates in the cecum. Additionally, these treatments improved the antioxidant and immune systems in chickens and restored all histopathological changes reported in the infected non-treated group (G2). This study offers novel perspectives on the potential anticoccidial effects of the combination of LF and diclazuril in broiler chickens infected with E. tenella, highlighting the potential synergistic actions of LF in treating poultry coccidiosis.