Improving medication adherence among persons with cardiovascular disease through m-health and community health worker-led interventions in Kerala; protocol for a type II effectiveness-implementation research-(SHRADDHA-ENDIRA).

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and at present, India has the highest burden of acute coronary syndrome and ST-elevation myocardial infarction (MI). A key reason for poor outcomes is non-adherence to medication. METHODS: The intervention is a 2 × 2 factorial design trial applying two interventions individually and in combination with 1:1 allocation ratio: (i) ASHA-led medication adherence initiative comprising of home visits and (ii) m-health intervention using reminders and self-reporting of medication use. This design will lead to four potential experimental conditions: (i) ASHA-led intervention, (ii) m-health intervention, (iii) ASHA and m-health intervention combination, (iv) standard of care. The cluster randomized trial has been chosen as it randomizes communities instead of individuals, avoiding contamination between participants. Subcenters are a natural subset of the health system, and they will be considered as the cluster/unit. The factorial cluster randomized controlled trial (cRCT) will also incorporate a nested health economic evaluation to assess the cost-effectiveness and return on investment (ROI) of the interventions on medication adherence among patients with CVDs. The sample size has been calculated to be 393 individuals per arm with 4-5 subcenters in each arm. A process evaluation to understand the effect of the intervention in terms of acceptability, adoption (uptake), appropriateness, costs, feasibility, fidelity, penetration (integration of a practice within a specific setting), and sustainability will be done. DISCUSSION: The effect of different types of intervention alone and in combination will be assessed using a cluster randomized design involving 18 subcenter areas. The trial will explore local knowledge and perceptions and empower people by shifting the onus onto themselves for their medication adherence. The proposal is aligned to the WHO-NCD aims of improving the availability of the affordable basic technologies and essential medicines, training the health workforce and strengthening the capacity of at the primary care level, to address the control of NCDs. The proposal also helps expand the use of digital technologies to increase health service access and efficacy for NCD treatment and may help reduce cost of treatment. TRIAL REGISTRATION: The trial has been registered with the Clinical Trial Registry of India (CTRI), reference number CTRI/2023/10/059095.

Assessment of Hearing in Patients with Head Injury: A Prospective Study.

Background: Hearing impairment is a well-known outcome of head trauma. The most prevalent site of injury is the peripheral structures. Hearing loss dissipates in most cases but can continue in some cases and may improve in some. Objectives: To evaluate the incidence of hearing loss and ascertain its type and degree in patients with head injury. To estimate the progression or regression of hearing loss in head injury patients during follow-up. Material and Methods: 60 patients with head injuries with any ear symptoms were included in the study. The severity of head injury is graded according to the Glasgow Coma Scale (GCS). Patients were subjected to High Resolution Computed Tomogram (HRCT) temporal bone, and Pure Tone Audiometry (PTA) was performed within 24 h of presenting. PTA repeated after 3 months. The degree of hearing loss and its progression or regression were assessed. Results: Of the 60 patients, 56 (93.3%) had hearing loss on PTA. 50 Cases (83.3%) showed conductive hearing loss (CHL). 6 (10%) had mixed hearing loss (MHL). 4 cases with MHL had a transverse temporal bone fracture on radiological evaluation. 41 (68.3%) had mild CHL, 4 (6.7%) had moderate MHL, and 2 (3.3%) had moderately severe MHL. PTA values reduced significantly from 1st to 2nd visit in both ears. Conclusion: In our study, there was significant improvement in hearing during follow-up, after 3 months of head injury indicating improvement in hearing. The improvement in hearing was noticed in all cases except for one case with transverse temporal bone fracture and moderately severe hearing loss. Routine otological examination should be considered in all patients with head injuries. Meticulous and timely management of these cases can significantly reduce morbidity in the patient.

Oral Squamous Cell Carcinoma of the Right Buccal Mucosa: A Case Report.

Oral squamous cell carcinoma (OSCC) is indeed one of the most common types of oral cancer, typically affecting individuals over the age of 50. It primarily originates from the squamous epithelial cells lining the oral cavity. While it is relatively rare in individuals under 40 years old, it can still occur, albeit less frequently in that age group. Risk factors for developing OSCC include tobacco use (smoking or chewing), excessive alcohol consumption, chronic irritation (such as from poorly fitting dentures), human papillomavirus (HPV), infection, and certain dietary foods. Early detection and treatment are crucial for improving outcomes and reducing the mortality associated with this type of cancer. This report describes a case of OSCC, staged T2 N0 M0, involving the right buccal mucosa of a 51-year-old male patient. The patient reported intense pain in an ulcer on the right side of his cheek. This report focuses on the etiological factors and a brief literature review of squamous cell carcinoma.

Influence of chitosan properties and operating parameters on the flocculation efficiency and harvesting of microalgae (Scenedesmus sp.).

Physicochemical and structural characteristics of chitosan prepared from Deep-sea shrimp (DCs), including degree of deacetylation (DD), molecular weight (Mw), viscosity, crystallinity index (CrI) and surface morphology were compared with a commercial chitosan (CCs). The DCs had a higher DD of 81.33 ± 0.40 %, whereas the CCs had a lower DD of 74.62 ± 0.64 %. Additionally, the DCs exhibited a lower Mw of 192.47 ± 2.5 kDa and viscosity of 646.00 ± 4.00 cP compared to the CCs, which had a Mw of 202.44 ± 0.28 kDa and viscosity of 689.67 ± 5.91 cP. This study investigated the influence of chitosan properties, particularly DD and Mw on the harvesting of Scenedesmus sp. along with the chitosan dosage, pH of the culture medium, mixing speed and time. Under optimal operating conditions, the microalgae removal efficiency of the DCs reached a significantly higher level (94.71 ± 0.20 %) compared to that of CCs (88.25 ± 0.41 %). Chitosan with a higher DD and low Mw demonstrated superior flocculation efficiency. The results highlight the significance of DD and Mw of chitosan and its influence on the flocculation of microalgae, providing valuable insights for optimizing the harvesting process with the non-toxic and natural flocculent, chitosan.

Olfactory Dysfunction in COVID-19 Patients in a Tertiary Care Hospital; A Cross-Sectional Observational Study.

Introduction: Sudden onset of olfactory dysfunction (OD) manifesting as hyposmia and/or anosmia occurred in many COVID-19 patients, with a frequency as high as 85.6%. Given the morbidity and mortality of COVID-19, it is important to recognize the symptoms early so that the infected person can be diagnosed, isolated and treated early. Hence, this study was undertaken to know the prevalence of Sino-nasal symptoms with special reference to olfactory dysfunction in COVID-19 patients. Materials and Methods: It is a cross sectional observational study involving 160 COVID-19 patients aged 18 to 100 years selected by universal sampling. OD was analyzed and compared with various inflammatory markers and Sino-nasal symptoms. Patients were followed up until their discharge from the hospital or until death due to COVID-19 related health issues. Results: Out of 160 subjects included in the study, 61.88 % of the study participants were males and 38.13% were females. The mean age was 44.50 ± 16.43 years. A total of 51 patients (31.87%) developed OD. Fifty one (31.87%) patients developed OD (anosmia/hyposmia). Among the individuals with anosmia/hyposmia, majority of patients (n=26) (50.98%) complained of more than 75% loss of smell sensation. Mean duration of anosmia/hyposmia was 9.92 ± 3.71 days. OD correlated with serum ferritin levels (p=0.0453). Conclusion: Anosmia/hyposmia was found in significant proportion of patients with covid-19 which correlated with the disease severity and serum ferritin levels and hence can serve as surrogate marker of disease severity.

Exploring the Structural Attributes of Yoda1 for the Development of New-Generation Piezo1 Agonist Yaddle1 as a Vaccine Adjuvant Targeting Optimal T Cell Activation.

Piezo1, a mechano-activated ion channel, has wide-ranging physiological and therapeutic implications, with the ongoing development of specific agonists unveiling cellular responses to mechanical stimuli. In our study, we systematically analyzed the chemical subunits in Piezo1 protein agonist Yoda1 to comprehend the structure-activity relationship and push forward next-generation agonist development. Preliminary screening assays for Piezo1 agonism were performed using the Piezo1-mCherry-transfected HEK293A cell line, keeping Yoda1 as a positive control. We introduce a novel Piezo1 agonist Yaddle1 (34, 0.40 µM), featuring a trifluoromethyl group, with further exploration through in vitro studies and density functional theory calculations, emphasizing its tetrel interactions, to act as an ambidextrous wedge between the domains of Piezo1. In contrast to the poor solubility of the established agonist Yoda1, our results showed that the kinetic solubility of Yaddle1 (26.72 ± 1.8 µM at pH 7.4) is 10-fold better than that of Yoda1 (1.22 ± 0.11 µM at pH 7.4). Yaddle1 (34) induces Ca2+ influx in human CD4+ T cell, suggesting its potential as a vaccine adjuvant for enhanced T cell activation.

Azole-based compounds as potential anti-Acanthamoeba agents.

Acanthamoeba castellanii is an opportunistic pathogen with public health implications, largely due to its invasive nature and non-specific symptoms. Our study focuses on the potential of azole compounds, particularly those with triazole scaffolds, as anti-amoebic agents. Out of 10 compounds, compounds T1 and T8 exhibited effective anti-Acanthamoeba activity with MIC50 values of 125.37 and 143.92 µg mL-1, respectively. Interestingly, compounds T1, T4, T5 and T8 revealed profound anti-excystation activity with MIC50 at 32.01, 85.53, 19.54 and 80.57 µg mL-1, respectively, alongside limited cytotoxicity to human cells. The study underscores the potential of T1, T4, T5, and T8, thiazole-based compounds, as anti-Acanthamoeba agents by both eliminating amoeba viability and preventing excystation, via preserving the amoeba in its latent cyst form, exposing them to elimination by the immune system. Notably, compounds T1, T4, T5, and T8 showed optimal molecular properties, moderate oral bioavailability, and stable complex formation with Acanthamoeba CYP51. They also display superior binding interactions. Further research is needed to understand their mechanisms and optimize their efficacy against Acanthamoeba infections.

NLRP3 inflammasome activity and periodontal disease pathogenesis-A bidirectional relationship.

OBJECTIVE: Periodontitis is an inflammatory oral disease that occurs as a result of the damaging effects of the immune response against the subgingival microflora. Among the mechanisms involved, the nucleotide-binding oligomerization domain, leucine-rich repeat-containing proteins family member NLRP3 (NLR family pyrin domain-containing 3), proposed as the key regulator of macrophage-induced inflammation, is strongly associated with periodontal disease due to the bacterial activators. This paper aimed to present key general concepts of NLRP3 inflammasome activation and regulation in periodontal disease. METHOD: A narrative review was conducted in order to depict the current knowledge on the relationship between NLRP3 inflammasome activity and periodontal disease. In vitro and in situ studies were retrieved and commented based on their relevance in the field. RESULTS: The NLRP3 inflammasome activity stimulated by periodontal microbiota drive periodontal disease pathogenesis and progression. This occurs through the release of proinflammatory cytokines IL-1ß, IL-18, and DAMPs (damage-associated molecular pattern molecules) following inflammasome activation. Moreover, the tissue expression of NLRP3 is dysregulated by oral microbiota, further exacerbating periodontal inflammation. CONCLUSION: The review provides new insights into the relationship between the NLRP3 inflammasome activity and periodontal disease pathogenesis, highlighting the roles and regulatory mechanism of inflammatory molecules involved in the disease process.

A Cadaveric Study on Perforator Anatomy of the Medial Sural Artery Perforator Flap.

Background The medial sural artery perforator (MSAP) flap was described by Cavadas et al in 2001. The aim of this study was to analyze the flap characteristics in the regional population and was planned as a cadaveric dissection study. Methods Thirty-three legs of fresh cadavers were studied for perforator characteristics, length, and origin of pedicle and skin paddle thickness. Observations were documented and analyzed. Results Seventeen right legs (51.5%) and sixteen left legs (48.5%) were studied. Twenty-five pedicles originated from popliteal artery (86.2%) and four (13.8%) from the common sural trunk. No perforators were seen in four legs. The mean number of perforators is 2 (0-6). The mean distance of perforator from midpoint of popliteal fossa was 10.7 cm (8-13 cm) and from posterior midline it was 3.2 cm. The mean size of the perforator was 1.1 ± 0.8 mm (0.8-1.5 mm). The mean pedicle length was 9.3 ± 1.3 cm. The mean flap thickness was 4.3 ± 0.7 mm (3.0-5.5 mm). There was no correlation for flap or perforator characteristics with side of leg. Conclusion This study concludes that MSAP is a good flap in terms of perforator characteristics, pedicle length, and flap thickness, when a medium sized thin flap with long pedicle is needed. The location of perforator on calf varies in different population. Being a perforator flap, anatomical variability is common and should be thought of while choosing this flap.

Synthesis, molecular docking studies and biological evaluation of N-(4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl) benzamides as potential antioxidant, and anticancer agents.

A series of novel chromone derivatives of (N-(4-oxo-2-(trifluoromethyl)-4H-chromen-6-yl) benzamides) were synthesized by treating 7-amino-2-(trifluoromethyl)-4H-chromen-4-one with K2CO3 and/or NaH, suitable alkyl halides and acetonitrile and/or 1,4-dioxane. The obtained products are in high yields (87 to 96%) with various substituents in short reaction times with no more by-products and confirmed by FT-IR, 1H, and 13C-NMR Spectral data. The in vitro cytotoxic activity was examined against two human cancer cell lines, namely the human lung adenocarcinoma (A-549) and the human breast (MCF-7) cancer cell line. Compound 4h showed promising cytotoxicity against both cell lines with IC50 values of 22.09 and 6.40 ± 0.26 µg/mL respectively, compared to that of the standard drug. We also performed the in vitro antioxidant activity by DPPH radical, hydrogen peroxide, NO scavenging, and total antioxidant capacity (TAC) assay methods, and they showed significant activities. The possible binding interactions of all the synthesized chromone derivatives are also investigated against selective pharmacological targets of human beings, such as HERA protein for cytotoxic activity and Peroxiredoxins (3MNG) for antioxidant activity which showed closer binding free energies than the standard drugs and evidencing the above two types of activities.

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study.

BACKGROUND: In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs). METHODS: After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device. RESULTS: From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV. CONCLUSION: Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.

Comparative Analysis of Machine-Learning Algorithms for Accurate Diagnosis of Lung Diseases Using Chest X-ray Images: A Study on Balanced and Unbalanced Data on Segmented and Unsegmented Images.

The study focused on the accurate diagnosis of lung diseases, considering the high number of lung disease-related deaths in the world. Chest x-ray images were used as they are a cost-effective and widely available diagnostic tool. Eight different machine learning algorithms were evaluated: Logistic Regression, Naive Bayes, k-Nearest Neighbors (kNN), Decision Tree, Random Forest, Support Vector Machine (SVM), Ridge, and Least Absolute Shrinkage and Selection Operator (LASSO). The study evaluated balanced and imbalanced datasets and looked at both segmented and unsegmented chest x-ray images. COVID-19, pneumonia, normal, and others were the four classes that were used in the investigation. Prior to attribute reduction, Decision Tree and Random Forest performed well on the balanced dataset, obtaining 74% test accuracy and 92% training accuracy. SVM functioned well as well, obtaining a 74% test accuracy. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) are two attribute reduction approaches that were applied. Decision Trees and Random Forests were able to attain the maximum training accuracy of 92%, while SVM was able to retain a test accuracy of 74% after attribute reduction. The findings also imply that some algorithms' performance may be enhanced by attribute reduction methods like PCA and LDA. For imbalanced data, Random Forest and SVM perform the best in terms of balanced accuracy of 80%. However, further research and experimentation may be needed to optimize the models and explore other potential algorithms or techniques.

Accelerating Charge Separation and CO2 Photoreduction in Aqueous Phase under Visible Light with Ru Nanoparticles Loaded on Ga-Doped NiTiO3 in a Batch Photoreactor.

Titanate perovskite (ATiO3) semiconductors show prospects of being active photocatalysts in the conversion of CO2 to chemical fuels such as methanol (CH3OH) in the aqueous phase. Some of the challenges in using ATiO3 are limited light-harvesting capability, rapid bulk charge recombination, and the low density of catalytic sites participating in CO2 reduction. To address these challenges, Ga-doped NiTiO3 (GNTO) photocatalysts in which Ga ions substitute for Ti ions in the crystal lattice to form electron trap states and oxygen vacancies have been synthesized in this work. The synthesized GNTO was then loaded with Ru nanoparticles to accelerate charge separation and enable excellent CO2 photoreduction activity under visible light. CO2 photoreduction was conducted in a batch photoreactor charged with a 0.1 M NaHCO3 aqueous solution at room temperature and a 3.5 bar pressure using a 1.0 wt % Ru-GNTO photocatalyst to yield methanol at a rate of 84.45 µmol g-1 h-1. A small amount of methane was produced as a side product at 21.35 µmol g-1 h-1, which is also a fuel molecule. We attribute this high catalytic activity toward CO2 photoreduction to a synergistic combination of our novel heterostructured 1.0 wt % Ru-GNTO photocatalyst and the implementation of a pressurized photoreactor. This work demonstrates an effective strategy for metal doping with active nanospecies functionality to improve the performance of ATiO3 photocatalysts in valorizing CO2 to solar fuels.

Injectable Extracellular Matrix-Inspired Hemostatic Hydrogel Composed of Hyaluronan and Gelatin with Shear-Thinning and Self-Healing.

Injectable ECM-inspired hydrogels composed of hyaluronic acid and gelatin are biocompatible and potentially useful for various medical applications. We developed injectable hydrogels composed of monoaldehyde-modified hyaluronic acid (HA-mCHO) and carbohydrazide-modified gelatin (GL-CDH), "HA/GL gel", whose ratios of HA-mCHO to GL-CDH were different. The hydrogels exhibited gelation times shorter than 3 s. In addition, the hydrogels showed strong shear-thinning and self-healing properties, mainly because of the dynamic covalent bonding of Schiff bases between HA-mCHO and GL-CDH. This hydrogel degraded in the mice's peritoneum for a week and showed excellent biocompatibility. Moreover, the hydrogel showed a higher breaking strength than fibrin glue in the lap shear test of porcine skin. Finally, the hydrogels decreased bleeding to as low as fibrin glue without using thrombin and fibrinogen in a mouse liver bleeding model in both single- and double-barreled syringe administrations. HA/GL gels have the potential for excellent biocompatibility and hemostasis in clinical settings.

Clinical Utility of Pro-inflammatory Oligomeric Glycoprotein Tenascin-C in the Diagnosis of Seropositive and Seronegative Rheumatoid Arthritis.

Owing to limited usefulness of Rheumatoid Factor and anti-CCP in rheumatoid arthritis, there is a need to identify a more sensitive and specific biomarker to detect rheumatoid arthritis (RA), particularly seronegative RA cases. Tenascin-C is an extracellular matrix glycoprotein, which has been implicated in the pathophysiology of RA. The objective of our study was to evaluate the diagnostic utility of serum Tenascin-C in seropositive and seronegative rheumatoid arthritis patients. We conducted a cross-sectional case control study. Sixty patients who fulfilled the ACR 2010 criteria for rheumatoid arthritis were included in the study. Thirty patients were found to be positive for RF and/or anti-CCP and 30 were negative for both RF and anti-CCP. Thirty age and gender-matched healthy subjects were taken as controls. Serum Tenascin-C was measured by quantitative sandwich enzyme immunoassay technique. The mean serum concentration of Tenascin-C in controls, seronegative and seropositive cases was 0.66 ng/ml, 20.54 ng/ml and 23.42 ng/ml, respectively. Tenascin-C levels were significantly higher in RA cases compared to controls (p < 0.0001). There was no significant difference in Tenascin-C between seropositive and seronegative cases (p = 0.603). ROC curve analysis showed a sensitivity of 96.6% and specificity of 100% with AUC of 0.98 at 2.21 ng/ml as cut-off value for diagnosing RA. Tenascin-C is elevated in both seronegative and seropositive RA, which indicates that it can be used as a sensitive marker for RA. The addition of Tenascin-C to the existing RF and anti-CCP may help in identifying a large number of patients with RA, particularly seronegative rheumatoid arthritis cases.

Climate influences scrub typhus occurrence in Vellore, Tamil Nadu, India: analysis of a 15-year dataset.

Climate is one of the major factors determining the prevalence and seasonality of vector borne diseases like scrub typhus (ST). We analyzed, the association of the meteorological factors like temperature, rainfall and humidity with scrub typhus using the 15 years scrub typhus data from a tertiary care hospital in Vellore, South India. Demographic data of permanent residents of Vellore, who had IgM ELISA results for scrub typhus for the time period of May 2005 to April 2020 were included. Meteorological data was correlated with the monthly scrub typhus cases; negative binomial regression model was used to predict the relation between scrub typhus occurrence and climate factors. Maximum number of ST cases were reported between the months August and February with October recording the highest number of cases. Elderly people, farmers, agricultural workers and housewives were at higher risk for scrub typhus. For an increase of 1 °C in mean temperature, the monthly ST cases reduced by 18.8% (95% CI - 24.1, - 13.2%). On the contrary, for 1 percent increase in mean relative humidity (RH), there is an increase of 7.6% (95% CI 5.4, 9.9%) of monthly ST cases. Similarly, an increase of 1 mm of rainfall contributed to 0.5 to 0.7% of monthly ST cases (after 2 months) depending on the variables included in the analysis. This study provides information that meteorological factors influence ST occurrence in Vellore. The rise of scrub typhus cases is maximal 2 months post rainfall. Whereas a rise in relative humidity, causes a rise in scrub typhus cases in same month, while rise in temperature has a negative impact on scrub typhus during the same month. These findings based on a retrospective analysis need validation by prospective studies.

Putative SNPs in Ovar-DRB1 and GALNTL6 Genes Conferring Susceptibility to Natural Infection of Haemonchus Contortus in Southern Indian Sheep.

AIM: To explore associations between phenotypic traits and polymorphisms in the DRB1 and GALNT6 gene in Nellore, Deccani and Kenguri sheep naturally infected with Haemonchus contortus. MATERIALS AND METHODS: Blood and faecal samples were collected to evaluate fecal worm egg counts (FEC), packed cell volume (PCV), hemoglobin (Hb), eosinophilia and for DNA isolation. RESULTS: Animals were grouped into susceptible and resistant groups based on EPG counts. FEC and circulating eosinophilia were higher in a susceptible group. Log FEC was negatively correlated (P < 0.01) with PCV, and Hb estimates. The second exon of DRB1 and intron variant of GALNTL6 genes were amplified from DNA samples of resistant and susceptible sheep. Characterization of Ovar-DRB1 amplicon by RFLP revealed two genotypes ('bb' and 'ab'). The genotype frequencies differed significantly between both groups (P < 0.05). The 'bb' genotypes had higher (P < 0.05) log FEC value than 'ab' genotypes and 'b' allele was linked with susceptibility to haemonchosis in sheep. The mean FEC of Nellore sheep was high indicating susceptibility of the breed and also in which the frequency of 'b' allele was more compared to the other two breeds. OVAR-DRB1 genotypes associated with FEC did not affect PCV and Hb. PCR-RFLP assay developed to determine the genotypes with respect to SNP rs424521894 of GALNTL6 revealed monomorphic nature at the locus in the breeds studied. CONCLUSION: MHC polymorphism could be used as a genetic marker for the selection of sheep resistant to H. contortus. However, a more intensive study, involving controlled infections and other GALNTL6 SNPs may be enforced to make any decisive assertion.

Injectable, shear-thinning, photocrosslinkable, and tissue-adhesive hydrogels composed of diazirine-modified hyaluronan and dendritic polyethyleneimine.

In the present study, we report the first synthesis of diazirine-modified hyaluronic acid (HA-DAZ). In addition, we also produced a precursor polymer solution composed of HA-DAZ and dendritic polyethyleneimine (DPI) that showed strong shear-thinning properties. Furthermore, its viscosity was strongly reduced (i.e., from 5 × 105 mPa s at 10-3 s-1 to 6 × 101 mPa s at 103 s-1), substantially, which enhanced solution injectability using a 21 G needle. After ultraviolet irradiation at 365 nm and 6 mW cm-2, the HA-DAZ/DPI solution achieved rapid gelation, as measured using the stirring method, and its gelation time decreased from 200 s to 9 s as the total concentrations of HA-DAZ and DPI increased. Following UV irradiation, the storage modulus increased from 40 to 200 Pa. In addition, reversible sol-gel transition and self-healing properties were observed even after UV irradiation. This suggests that the HA-DAZ/DPI hydrogel was crosslinked in multiple ways, i.e., via covalent bonding between the diazirine and amine groups and via intermolecular interactions, including hydrogen bonding, electrostatic interactions, and hydrophobic interactions. A lap shear test showed that the HA-DAZ/DPI hydrogel exhibited strong adhesiveness as a fibrin glue following UV irradiation. Finally, the HA-DAZ/DPI hydrogel showed higher tissue reinforcement than fibrin glue in an ex vivo burst pressure test of the porcine esophageal mucosa.

Tannerella forsythia scavenges Fusobacterium nucleatum secreted NOD2 stimulatory molecules to dampen oral epithelial cell inflammatory response.

The oral organism Tannerella forsythia is auxotrophic for peptidoglycan amino sugar N-acetylmuramic acid (MurNAc). It survives in the oral cavity by scavenging MurNAc- and MurNAc-linked peptidoglycan fragments (muropeptides) secreted by co-habiting bacteria such as Fusobacterium nucleatum with which it forms synergistic biofilms. Muropeptides, MurNAc-l-Ala-d-isoGln (MDP, muramyl dipeptide) and d-γ-glutamyl-meso-DAP (iE-DAP dipeptide), are strong immunostimulatory molecules that activate nucleotide oligomerization domain (NOD)-like innate immune receptors and induce the expression of inflammatory cytokines and antimicrobial peptides. In this study, we utilized an in vitro T. forsythia-F. nucleatum co-culture model to determine if T. forsythia can selectively scavenge NOD ligands from the environment and impact NOD-mediated inflammation. The results showed that NOD-stimulatory molecules were secreted by F. nucleatum in the spent culture broth, which subsequently induced cytokine and antimicrobial peptide expression in oral epithelial cells. In the spent broth from T. forsythia-F. nucleatum co-cultures, the NOD-stimulatory activity was significantly reduced. These data indicated that F. nucleatum releases NOD2-stimulatory muropeptides in the environment, and T. forsythia can effectively scavenge the muropeptides released by co-habiting bacteria to dampen NOD-mediated host responses. This proof-of-principle study demonstrated that peptidoglycan scavenging by T. forsythia can impact the innate immunity of oral epithelium by dampening NOD activation.