A diet rich in omega-3 fatty acid improves periodontitis and tissue destruction by MMP2- and MMP9-linked inflammation in a murine model.

Periodontitis is an oral-cavity inflammatory disease and is the principal cause associated with tooth loss. Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are important proteases involved in periodontal tissue destruction. The omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been demonstrated to possess immunoregulatory properties in periodontitis. The aim of the study was to investigate the effects of ω-3 PUFA on inflammation and on the expression of MMP-2 and -9 in a murine periodontitis model. Twenty-four male C57BL/6 mice were divided into control mice (Control), control mice treated with ω-3 PUFA (O3), mice with periodontitis (P), and mice with periodontitis treated with ω-3 PUFA (P + O3). ω-3 PUFA were administered orally once a day for 70 days. Periodontitis in mice was induced by Porphyromonas gingivalis-infected ligature placement around the second maxillary molar. The mice were sacrificed, and blood and maxillary samples were collected. Flow cytometry was used to quantify tumor necrosis factor-alpha (TNFα), interleukin (IL)-2, IL-4, IL-5, and interferon-gamma. Histologic analysis and immunohistochemistry for MMP-2 and -9 were performed. The data were statistically evaluated using analysis of variance (ANOVA) and the Tukey post hoc test. Histological analysis showed that ω-3 PUFA supplementation prevented inflammation and tissue destruction and revealed that bone destruction was more extensive in the P group than in the P + O3 group (p < 0.05). Also, it decreased the serum expressions of TNFα and IL-2 and the tissue expression of MMP-2 and -9 in the periodontitis-induced model (p < 0.05). ω-3 PUFA supplementation prevented alveolar bone loss and periodontal destruction, probably by decreasing the expression of MMP-2 and MMP-9 and its immunoregulatory properties.

Suicide by ligature strangulation and/or hanging inside a motor vehicle: a comprehensive review.

Suicide by ligature strangulation/hanging inside vehicles is uncommon, and only few cases have been reported in the literature. This study aimed to conduct a comprehensive review of reported cases of suicide by ligature strangulation/hanging inside vehicles, analyzing the features of the death scene, of the ligature and furrow, autopsy findings, and causes of death. The comprehensive review was performed following the PRISMA guidelines by using the most common scientific databases. According to inclusion criteria, a total of 20 cases of vehicle-assisted strangulation/hanging were reviewed: 13 cases were assessed as ligature strangulation resulting in 7 complete decapitations and 7 other cases as hanging. All victims were young or adult males, except for one 48-year-old female. Death was assessed as suicide in all cases, except for a possible accidental autoerotic death. In 8 cases, a history of depression or other psychiatric disorders was reported. Toxicological analysis were positive in 7 cases. Hard ligature materials (nylon, steel, plastic, hemp ropes) were used in most cases, but only 13 cases had a well-demarcated furrow. In 2 cases, no internal findings of asphyxia were found. An additional case of ligature strangulation inside a motor vehicle off is also presented, where no autopsy findings of asphyxia were observed, except for a broad pale furrow and monolateral conjunctival petechiae. This study highlights the challenges in classifying suicidal hanging and ligature strangulation in motor vehicles.

The orthodontic treatment and the periodontal status of patients.

OBJECTIVE: Aim: To review and analyze modern professional literature on the impact of orthodontic treatment of maxillofacial anomalies on the periodontal status of patients, in particular, the subsiqent pathogenetic mechanisms of the development of periodontal diseases in this category of patients. PATIENTS AND METHODS: Materials and Methods: Bibliometric and analytical methods were used data from international scientific sources in the field of studying the impact of orthodontic treatment on the state of periodontal tissues were used. Conclusions: Patients undergoing orthodontic treatment need the increased attention to the state of periodontal tissues and regular high-quality both professional and individual oral hygiene. A comprehensive approach to treatment and preventive measures for periodontal diseases, taking into account all pathogenetic links of their development in this category of patients, aims not only to keep the periodontium healthy, but also to ensure successful completion of orthodontic treatment. Taking into account consideration the periodontal status of patients allows individual correction of the treatment plan to increase its clinical effectiveness both in the early and in the long term.

FasL is a catabolic factor in alveolar bone homeostasis.

AIM: Fas ligand (FasL) belongs to the tumour necrosis factor superfamily regulating bone turnover, inflammation, and apoptosis. The appendicular and axial skeleton phenotype of mature Faslgld mice has been reported. The impact of FasL on the alveolar bone providing support for the teeth at mature stages under healthy and induced inflammatory conditions remains unknown. MATERIALS AND METHODS: We performed a phenotypical analysis of mice carrying the homozygous Faslgld mutation and wild-type (WT) mice (C57BL/6) under healthy conditions and upon ligature-induced periodontitis. After 12 days, micro-computed tomography analysis revealed the distance between the cement enamel junction and the alveolar bone crest. Additional structural parameters, such as the bone volume fraction (BV/TV) and the periodontal ligament space volume, were measured. Histological analyses were performed to visualize the catabolic changes at the defect site. RESULTS: Healthy Faslgld mice were found to have more periodontal bone than their WT littermates. Faslgld had no significant effect on inflammatory osteolysis compared to WT controls with ligatures. Histology revealed eroded surfaces at the root and in the inter-proximal bone in both strains. CONCLUSIONS: Our findings suggest that FasL is a catabolic factor in alveolar bone homeostasis but it does not affect the inflammatory osteolysis.

Right portal vein ligation is still relevant for left hemi-liver hypertrophy: results of a comparative study using a propensity score between right portal vein ligation and embolization.

BACKGROUND: In two-stage hepatectomy for bilobar liver metastases from colorectal cancer, future liver remnant (FLR) growth can be achieved using several techniques, such as right portal vein ligation (RPVL) or right portal vein embolization (RPVE). A few heterogeneous studies have compared these two techniques with contradictory results concerning FLR growth. The objective of this study was to compare FLR hypertrophy of the left hemi-liver after RPVL and RPVE. STUDY DESIGN: This was a retrospective comparative study using a propensity score of patients who underwent RPVL or RPVE prior to major hepatectomy between January 2010 and December 2020. The endpoints were FLR growth (%) after weighting using the propensity score, which included FLR prior to surgery and the number of chemotherapy cycles. Secondary endpoints were the percentage of patients undergoing simultaneous procedures, the morbidity and mortality, the recourse to other liver hypertrophy procedures, and the number of invasive procedures for the entire oncologic program in intention-to-treat analysis. RESULTS: Fifty-four consecutive patients were retrospectively included and analyzed, 18 in the RPVL group, and 36 in the RPVE group. The demographic characteristics were similar between the groups. After weighting, there was no significant difference between the RPVL and RPVE groups for FLR growth (%), respectively 32.5% [19.3-56.0%] and 34.5% [20.5-47.3%] (p = 0.221). There was no significant difference regarding the secondary outcomes except for the lower number of invasive procedures in RPVL group (median of 2 [2.0, 3.0] in RPVL group and 3 [3.0, 3.0] in RPVE group, p = 0.001)). CONCLUSION: RPVL and RPVE are both effective to provide required left hemi-liver hypertrophy before right hepatectomy. RPVL should be considered for the simultaneous treatment of liver metastases and the primary tumor.

Periodontitis-induced neuroinflammation impacts dendritic spine immaturity and cognitive impairment.

OBJECTIVE: This study investigated the spinal changes in ligature-induced periodontitis and the role of periodontitis in cognitive impairment. METHODS: Twenty mice were randomized into the control and chronic periodontitis (CP) groups, with the latter receiving ligature-induced periodontitis. Cognitive performance was assessed by fear conditioning test. Periodontal inflammation and alveolar bone resorption were evaluated by micro-computed tomography and histopathology. The hippocampal microglial activation was evaluated by immunohistochemistry (IHC). The expressions of hippocampal cytokines (TNF-α, iNOS, IL-1ß, IL-4, IL-10, and TREM2) were measured by reverse transcription-polymerase chain reaction. The morphology and density of the dendritic spines were determined by Golgi-Cox staining. RESULTS: The CP mice reported significant inflammatory cell infiltration and alveolar bone resorption, with marked increases in cytokine levels (TNF-α, iNOS, IL-1ß, and TREM2) in the brain. Moreover, the CP mice showed significantly reduced freezing to the conditioned stimulus in the cued and contextual tests, indicating impaired memory. Further analyses revealed, in the hippocampus of the CP mice, enhanced microglial activation, decreased dendritic spine density, and increased proportion of thin dendritic spines. CONCLUSIONS: Periodontitis-induced neuroinflammation may impair the cognitive function by activating hippocampal microglia and inducing dendritic spine immaturity.

Experimental model of periodontitis and rheumatoid arthritis potentiates the deleterious effects on functional capacity, leukocyte migration, synovial and periodontal tissues in Wistar rats.

OBJECTIVE: This study aimed to evaluate whether ligature-induced periodontitis and rheumatoid arthritis (RA) potentiate the deleterious effects on functional capacity, periodontal and synovial tissues, leukocyte migration, and interleukin 17 (IL-17) levels, and to investigate the repercussions of single Freund's Complete Adjuvant (FCA) injection associated with periodontitis. MATERIALS AND METHODS: Fifty-one male Wistar rats were randomised into six groups: control (CG, n = 8), RA (RAG, n = 9), periodontitis (PG, n = 9), periodontitis and RA (PRAG, n = 9), periodontitis and intradermal injection (PIDG, n = 9), and periodontitis and intra-articular injection (PIAG, n = 7). The animals underwent ligature placement and one or two injections with FCA to induce RA. Motor disability, nociceptive threshold, joint edema, and muscle strength were assessed, and the animals were euthanized on day 30. Synovial fluid, hemimandibles, and knee joints were collected. RESULTS: PRAG showed no reduction of edema or improvement of muscle strength, whereas it showed most significant changes in leukocyte migration, morphological analyses of the synovial membrane (SM), and radiographic and histometric analyses of the jaw. The PIAG showed some alterations, though not permanent. CONCLUSION: Ligature-induced periodontitis and RA induced by two FCA injections accentuated the deleterious effects on functional capacity, leukocyte migration, synovial and periodontal tissues.

Anti-Periodontitis Effects of Dendropanax morbiferus H.Lév Leaf Extract on Ligature-Induced Periodontitis in Rats.

Periodontitis is caused by pathogens in the oral cavity. It is a chronic infectious disease that causes symptoms including gingival bleeding and tooth loss resulting from the destruction of periodontal tissues coupled with inflammation. Dendropanax morbiferus H.Lév (DM) is a natural product that exhibits various biological activities with few side effects. In this study, the potential of DM leaf hot-water extracts (DMWE) as a treatment for periodontitis was determined and its anti-oxidant and anti-inflammatory effects were evaluated. Compounds in DMWE were identified by high-performance liquid chromatography (HPLC) and nitric oxide (NO) and prostaglandin E2 (PGE2) production was measured in RAW 264.7 cells. We measured the gingival index and gingival sulcus depth, and micro-CT was performed in vivo using a ligature-induced periodontitis rat model, which is similar to human periodontitis. The DMWE-treated group exhibited a decrease in cytokine concentration and relieved the gingival index and gingival sulcus depth compared with the periodontitis-induced control group. In addition, micro-CT and histological analysis revealed that DMWE exhibited anti-inflammatory effects and improved alveolar bone loss in periodontitis-induced rats. These findings suggest that DMWE has excellent anti-oxidant and anti-inflammatory effects that protect and prevent periodontal tissue damage and tooth loss caused by the inflammatory response.

SURGICAL TREATMENT OPTIMISATION OF RECURRENT ABDOMINAL WALL HERNIAS ASSOCIATED WITH LIGATURE FISTULA.

OBJECTIVE: The aim: To improve the efficiency of treatment of recurrent abdominal wall hernia associated with ligature fistula. PATIENTS AND METHODS: Materials and methods: We analysed the results of treatment of recurrent hernias with ligature fistula in 86 patients. 44 patients of group 1 were treated according to the developed algorithm (fistula and mesh explantation, wound debridement, mesh fixation and wound closure with antiseptic-containing polyurethane composite), 42 patient (group 2) were treated according to the traditional one. RESULTS: Results: Decreased rate of seroma formation in group 1 if compared to group 2 was observed up to 6,7% against 23,8% (OR=0,23; 95%CI=0,06-0,92; р=0,038). Wound infection occurred in 1 (2,3%) case of group 1 against 7 (16,7%) of group 2 (OR= 0,12; 95% CI =0,01-0,99; р=0,027). 4 (9,5%) patients from group 2 developed recurrent ligature fistula (OR= 0,10; 95%CI= 0,01-1,90). Recurrence of hernia was observed in 1 (2,9%) patient of group 1 against 6 (17,7%) patients of group 2 (OR=0,14; 0,01-1,21; р=0,048). CONCLUSION: Conclusions: Surgical treatment optimisation of recurrent abdominal wall hernia associated with ligature fistula improved the efficiency of treatment, which was proven by the obtained outcomes and relative risk of complications.

Exosomes from dental pulp cells attenuate bone loss in mouse experimental periodontitis.

BACKGROUND AND OBJECTIVE: Exosomes are small vesicles secreted from many cell types. Their biological effects largely depend on their cellular origin and the physiological state of the originating cells. Exosomes secreted by mesenchymal stem cells exert therapeutic effects against multiple diseases and may serve as potential alternatives to stem cell therapies. We previously established and characterized human leukocyte antigen (HLA) haplotype homo (HHH) dental pulp cell (DPC) lines from human wisdom teeth. In this study, we aimed to investigate the effect of local administration of HHH-DPC exosomes in a mouse model of periodontitis. METHODS: Exosomes purified from HHH-DPCs were subjected to particle size analysis, and expression of exosome markers was confirmed by western blotting. We also confirmed the effect of exosomes on the migration of both HHH-DPCs and mouse osteoblastic MC3T3-E1 cells. A mouse experimental periodontitis model was used to evaluate the effect of exosomes in vivo. The morphology of alveolar bone was assessed by micro-computed tomography (µCT) and histological analysis. The effect of exosomes on osteoclastogenesis was evaluated using a co-culture system. RESULTS: The exosomes purified from HHH-DPCs were homogeneous and had a spherical membrane structure. HHH-DPC exosomes promoted the migration of both human DPCs and mouse osteoblastic cells. The MTT assay showed a positive effect on the proliferation of human DPCs, but not on mouse osteoblastic cells. Treatment with HHH-DPC exosomes did not alter the differentiation of osteoblastic cells. Imaging with µCT revealed that the exosomes suppressed alveolar bone resorption in the mouse model of periodontitis. Although no change was apparent in the dominance of TRAP-positive osteoclast-like cells in decalcified tissue sections upon exosome treatment, HHH-DPC exosomes significantly suppressed osteoclast formation in vitro. CONCLUSIONS: HHH-DPC exosomes stimulated the migration of human DPCs and mouse osteoblastic cells and effectively attenuated bone loss due to periodontitis.

High-frequency pulsed diode laser irradiation inhibits bone resorption in mice with ligature-induced periodontitis.

AIM: The purpose of this study was to elucidate the suppressive effect of high-frequency pulsed diode laser irradiation on bone resorption and its biological effects on gene expression and microbiome composition on the gingival tissue in ligature-induced periodontitis in mice. MATERIALS AND METHODS: Ligating ligature around the teeth and/or laser irradiation was performed on the gingival tissue in mice as follows: Co (no ligature and no laser irradiation), Li (ligation without laser irradiation), La (no ligature but with laser irradiation), and LiLa (ligation with laser irradiation). Bone resorption was evaluated using micro-computed tomography. RNA-seq analysis was performed on gingival tissues of all four groups at 3 days after ligation. The differences in microbial composition between Li and LiLa were evaluated based on the number of 16S rRNA gene sequences. RESULTS: Bone resorption caused by ligation was significantly suppressed by laser irradiation. RNA-seq in Co and La gingival tissue revealed many differentially expressed genes, suggesting diode laser irradiation altered gene expression. Gene set enrichment analysis revealed mTORC1 signalling and E2F target gene sets were enriched in gingival tissues both in La and LiLa compared with that in Co and Li, respectively. The amount of extracted DNA from ligatures was reduced by laser irradiation, and bacterial network structure was altered between the Li and LiLa. CONCLUSIONS: High-frequency pulsed diode laser irradiation showed biological effects and suppressed bone resorption in ligature-induced periodontitis.

Directive clinique no 424 : Prise en charge du cordon ombilical chez le nourrisson prématuré ou à terme.

OBJECTIF: Évaluer l'effet du clampage retardé du cordon et de la traite du cordon ombilical sur les risques de mortalité et de morbidité maternelles et néonatales en contexte de grossesses monofœtale ou gémellaire. POPULATION CIBLE: Femmes enceintes dont la grossesse monofœtale ou gémellaire est à terme ou avant terme. BéNéFICES, RISQUES ET COûTS: Chez les prématurés de grossesse monofœtale, le clampage retardé de 60 à 120 secondes idéalement, mais d'au moins 30 secondes, réduit le risque de mortalité et de morbidité. Chez les jumeaux prématurés, le clampage retardé est associé à certains bénéfices. Chez les nourrissons de grossesse monofœtale à terme, le clampage retardé de 60 secondes améliore les paramètres hématologiques. Chez les grands prématurés, la traite du cordon ombilical augmente le risque d'hémorragie intraventriculaire. DONNéES PROBANTES: Une recherche a été effectuée au moyen des bases de données Medline, PubMed, Embase et Cochrane Library, de leur création jusqu'à mars 2020, à partir de termes MeSH et de mots clés liés au clampage retardé du cordon et à la traite du cordon ombilical. Le présent document est un résumé des données probantes et non pas une revue méthodologique. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CIBLES: Fournisseurs de soins de maternité et néonataux.

The optimization of ligature/bone defect-induced periodontitis model in rats.

The destruction of alveolar bone is a crucial manifestation of severe chronic periodontitis, which stem cell-based bioengineered therapies are expected to cure. Therefore, a cost-effective, reproducible, quantifiability and easier to administrate animal model that mimics human periodontitis is of great importance for further endeavor. In this study, we created periodontitis rat models in silk ligation group, bone defect group and bone defect/silk ligation group, respectively. Obvious periodontal inflammation but slight alveolar bone resorption was observed in the ligation group, while surgical trauma was not robust enough to continually worsen the constructed bone defect area in the bone defect group. In the bone defect/ligature group, significant and stable periodontal inflammation was the most enduring with similar evolving pathological patterns of human periodontitis. It also exhibited enhanced clinical similarity and confirmed its superiority in quantitativeness. The present rat model is the first study to reproduce a pathological process similar to human periodontitis with reliable stability and repeatability, manifesting a priority to previous methods. Day 9-12 is the best time for reproducing severe periodontitis syndromes with vertical bone resorption in this model.

The Treatment Efficiency and Microbiota Analysis of Sapindus mukorossi Seed Oil on the Ligature-Induced Periodontitis Rat Model.

Periodontitis is a common oral disease mainly caused by bacterial infection and inflammation of the gingiva. In the prevention or treatment of periodontitis, anti-bacterial agents are used to inhibit pathogen growth, despite increasing levels of bacterial resistance. Sapindus mukorossi Gaertn (SM) seed oil has proven anti-bacterial and anti-inflammation properties. However, the possibility of using this plant to prevent or treat periodontitis has not been reported previously. The aim of this study was to evaluate the effects of SM oil on experimental periodontitis in rats by using micro-CT and microbiota analysis. The distance between cementoenamel junction (CEJ) and alveolar bone crest (ABC) on the sagittal micro-CT slide showed that total bone loss (TBL) was significantly lower in CEJ-ABC distances between SM oil and SM oil-free groups on Day 14. Histology data also showed less alveolar bone resorption, a result consistent result with micro-CT imaging. The microbiota analyzed at phylum and class levels were compared between the SM oil and SM oil-free groups on Day 7 and Day 14. At the phylum level, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were the dominant bacterium. Firmicutes in box plot analysis was significantly less in the SM oil group than in the SM oil-free group on Day 7. At the class level, Bacteroidia, Gammaproteobacteria, Bacilli, Clostridia, and Erysipelotrichia were the dominant bacteria. The bacteria composition proportion of Bacilli, Clostridiay, and Erysipelotrichia could be seen in the SM oil group significantly less than in t SM oil-free group on Day 7. Overall, the present results show that topical application of SM oil can reduce bone resorption and change bacteria composition in the ligature-induced periodontitis model. According to these results, it is reasonable to suggest SM oil as a potential material for preventing oral disease.

Comparison of the incidence of intra-operative haemorrhage from ovarian vessels during ovariectomy and ovariohysterectomy of dogs and cats performed by inexperienced surgeons using surgeon's and constrictor knots.

AIMS: To compare the incidence of intra-operative haemorrhage from ovarian vessels during ovariectomy (OV) and ovariohysterectomy (OVH) in dogs and cats performed by inexperienced surgeons using surgeon's and constrictor knots to ligate the ovarian pedicles. METHODS: All client-owned female dogs (n = 51) and cats (n = 102) that presented for OV or OVH at two referral clinics in Belgium and France from January to June 2019 were included. Surgeries were performed by inexperienced surgeons under the supervision of diplomates or residents of the European College of Veterinary Surgeons. During routine and emergency OV or OVH one pedicle of each animal was ligated using a constrictor knot and the other with a surgeon's knot, the side assigned randomly. Time taken to perform each knot and the number of ligatures that resulted in intraoperative haemorrhage from the ovarian vessels were recorded. Body condition score (BCS) was recorded for 33 dogs and 22 cats. RESULTS: The median time taken to perform constrictor knots in dogs (81 seconds), was longer than for surgeon's knots (69 seconds; p = 0.005). In cats, the median time taken to perform constrictor knots (109 seconds) was also longer than for surgeon's knots (90.5 seconds; p = 0.02).The number of dogs that had intra-operative haemorrhages from pedicles ligated with constrictor knots (2/102; 3.9%) was less than those ligated with surgeon's knots (10/102; 19.6%; p = 0.027). The median BCS of dogs that experienced haemorrhage (n = 8; median 5/9, min 3/9, max 7/9) was higher (p = 0.019) than that of dogs that did not experience haemorrhage (n = 25; median 4/9, min 3/9, max 8/9).There was no evidence (p = 1.0) of a difference in the proportion of cats that experienced intra-operative haemorrhage from pedicles ligated with constrictor knots (3/44; 6.8%) and those ligated with surgeon's knots (2/44; 4.5%). Two-thirds of the haemorrhages with constrictor knots were caused by pedicle rupture during tightening. CONCLUSIONS: The rate of intraoperative haemorrhage from the ovarian pedicle was lower when a constrictor knot was used compared to a surgeon's knot in dogs but not in cats. While the constrictor knot was more time consuming to tie this is not likely to have a clinical impact. Use of this knot by inexperienced surgeons in dogs may help to reduce the risk of intraoperative haemorrhage during OVH/OV.

DIRECTIVE CLINIQUE CONJOINTE DE LA SOGC ET DE LA SCP: Directive clinique no 424 : Prise en charge du cordon ombilical chez le nourrisson prématuré ou à terme.

Objectif: Évaluer l'effet du clampage retardé du cordon et de la traite du cordon ombilical sur les risques de mortalité et de morbidité maternelles et néonatales en contexte de grossesses monofœtale ou gémellaire. Population cible: Femmes enceintes dont la grossesse monofœtale ou gémellaire est à terme ou avant terme. Bénéfices risques et coûts: Chez les prématurés de grossesse monofœtale, le clampage retardé de 60 à 120 secondes idéalement, mais d'au moins 30 secondes, réduit le risque de mortalité et de morbidité. Chez les jumeaux prématurés, le clampage retardé est associé à certains bénéfices. Chez les nourrissons de grossesse monofœtale à terme, le clampage retardé de 60 secondes améliore les paramètres hématologiques. Chez les grands prématurés, la traite du cordon ombilical augmente le risque d'hémorragie intraventriculaire. Données probantes: Une recherche a été effectuée au moyen des bases de données Medline, PubMed, Embase et Cochrane Library, de leur création jusqu'à mars 2020, à partir de termes MeSH et de mot-clés liés au clampage retardé du cordon et à la traite du cordon ombilical. Le présent document est un résumé des données probantes et non pas une revue méthodologique. Méthodes de validation: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]).

Activated STAT3 signaling pathway by ligature-induced periodontitis could contribute to neuroinflammation and cognitive impairment in rats.

BACKGROUND: Increasing evidence suggests a causal link between periodontitis and cognitive disorders. Systemic inflammation initiated by periodontitis may mediate the development of cognitive impairment. Our study aims to investigate the effect of ligature-induced periodontitis on cognitive function and the role of signal transducers and activators of transcription 3 (STAT3) in this process. MATERIALS AND METHODS: Ligature-induced periodontitis was established, and the rats were treated intraperitoneally with/without the pSTAT3 inhibitor cryptotanshinone (CTS). Alveolar bone resorption and periodontal inflammation were detected by micro-computed tomography analysis and histopathological evaluation. Locomotor activity and cognitive function were evaluated by the open field test and the Morris water maze test, respectively. The activation of microglia and astrocytes in the hippocampus and cortex was assessed by immunohistochemistry (IHC). The expression of interleukins (IL-1ß, IL-6, IL-8, IL-21) in both the periphery and cortex was evaluated by RT-PCR and ELISA. The expression of TLR/NF-κB and ROS cascades was evaluated by RT-PCR. The expression of pSTAT3 and the activation of the STAT3 signaling pathway (JAK2, STAT3, and pSTAT3) in the periodontal tissue and cortex were assessed by IHC and Western blot. The expression of amyloid precursor protein (APP) and its key secretases was evaluated by RT-PCR. The level of amyloid ß-protein (Aß) and the ratio of Aß1-40/1-42 were measured via ELISA in the plasma and cortex while IHC was used to detect the level of Aß1-42 in the brain. RESULTS: In periodontal ligature rats, significant alveolar bone resorption and local inflammatory cell infiltration were present. Apparent increases in inflammatory cytokines (IL-1ß, IL-6, IL-8, and IL-21) were detected in peripherial blood and brain. Additionally, spatial learning and memory ability was impaired, while locomotor activity was not affected. Activated microglia and astrocytes were found in the cortex and hippocampus, presenting as enlarged cell bodies and irregular protrusions. Levels of TLR/NF-kB, PPAR and ROS were altered. The STAT3 signaling pathway was activated in both the periodontal tissue and cortex, and the processing of APP by ß- and γ-secretases was promoted. The changes mentioned above could be relieved by the pSTAT3 inhibitor CTS. CONCLUSIONS: Ligature-induced periodontitis in rats resulted in systemic inflammation and further abnormal APP processing, leading to cognitive impairments. In this progress, the activation of the STAT3 signaling pathway may play an important role by increasing inflammatory load and promoting neuroinflammation.

Genetically engineered E. coli Nissle attenuates hyperammonemia and prevents memory impairment in bile-duct ligated rats.

Hyperammonemia associated with chronic liver disease (CLD) is implicated in the pathogenesis of hepatic encephalopathy (HE). The gut is a major source of ammonia production that contributes to hyperammonemia in CLD and HE and remains the primary therapeutic target for lowering hyperammonemia. As an ammonia-lowering strategy, Escherichia coli Nissle 1917 bacterium was genetically modified to consume and convert ammonia to arginine (S-ARG). S-ARG was further modified to additionally synthesize butyrate (S-ARG + BUT). Both strains were evaluated in bile-duct ligated (BDL) rats; experimental model of CLD and HE. METHODS: One-week post-surgery, BDLs received non-modified EcN (EcN), S-ARG, S-ARG + BUT (3x1011 CFU/day) or vehicle until sacrifice at 3 or 5 weeks. Plasma (ammonia/pro-inflammatory/liver function), liver fibrosis (hydroxyproline), liver mRNA (pro-inflammatory/fibrogenic/anti-apoptotic) and colon mRNA (pro-inflammatory) biomarkers were measured post-sacrifice. Memory, motor-coordination, muscle-strength and locomotion were assessed at 5 weeks. RESULTS: In BDL-Veh rats, hyperammonemia developed at 3 and further increased at 5 weeks. This rise was prevented by S-ARG and S-ARG + BUT, whereas EcN was ineffective. Memory impairment was prevented only in S-ARG + BUT vs BDL-Veh. Systemic inflammation (IL-10/MCP-1/endotoxin) increased at 3 and 5 weeks in BDL-Veh. S-ARG + BUT attenuated inflammation at both timepoints (except 5-week endotoxin) vs BDL-Veh, whereas S-ARG only attenuated IP-10 and MCP-1 at 3 weeks. Circulating ALT/AST/ALP/GGT/albumin/bilirubin and gene expression of liver function markers (IL-10/IL-6/IL-1ß/TGF-ß/α-SMA/collagen-1α1/Bcl-2) were not normalized by either strain. Colonic mRNA (TNF-α/IL-1ß/occludin) markers were attenuated by synthetic strains at both timepoints vs BDL-Veh. CONCLUSION: S-ARG and S-ARG + BUT attenuated hyperammonemia, with S-ARG + BUT additional memory protection likely due to greater anti-inflammatory effect. These innovative strategies, particularly S-ARG + BUT, have potential to prevent HE.

Hangings: Lessons Learned from the Coroner's Office.

BACKGROUND: Hangings are an infrequent wounding mechanism among patients arriving alive to hospital but are frequently encountered by the Coroner's Office. It is unclear if classically described hanging injuries, such as the Hangman's fracture, are common among contemporary hangings patients who typically do not suspend from height. This study was undertaken to define patient and injury characteristics after hangings causing death. METHODS: All patients presenting to the Los Angeles County Medical Examiner/Coroner's Office (January 2016 - May 2020) who died by hanging were included. Demographics, psychiatric history, hanging details, autopsy type, and sustained injuries were collected. Data variables were summarized with descriptive statistics and the diagnostic yield of a ligature mark in the diagnosis/exclusion of cervical injuries was calculated. RESULTS: Over the study, 1,401 patients died by hanging. Patients underwent external exam alone (n = 1,282, 92%), traditional neck autopsy (n = 114, 8%), or traditional neck autopsy plus postmortem computed tomography scan (n = 5, <1%). Home was the most frequent hanging setting (n = 1,028, 73%) followed by public spaces (n = 80, 6%) and jail (n = 28, 2%). The manner of death was almost exclusively suicide (n = 1,395, >99%) and psychiatric disease was common (n = 968, 69%). Of the patients undergoing traditional autopsy, most had a ligature mark (n = 109, 92%) and only 9 (8%) had a cervical injury (hyoid fractures, n = 6, 5%; thyroid cartilage fractures, n = 4, 3%). None had a vertebral fracture/dislocation. Sensitivity, specificity, positive predictive value, and negative predictive value of a ligature mark were 100%, 5%, 8%, and 100%. CONCLUSIONS: Hangings are a frequent cause of death in Los Angeles County. Patients typically have a psychiatric history and die almost exclusively from suicide. Hangings commonly occur at home, in public places, and in jail. Injuries were exceedingly rare and no patient sustained a Hangman's fracture, which may be related to the lack of significant suspension with modern hangings.

Ethanol consumption increases renal dysfunction and mortality in a mice model of sub-lethal sepsis.

Chronic ethanol consumption and sepsis cause oxidative stress and renal dysfunction. This study aimed to examine whether chronic ethanol consumption sensitizes the mouse kidney to sub-lethal cecal ligation and puncture (SL-CLP) sepsis, leading to impairment of renal function by tissue oxidative and inflammatory damage. Male C57BL/6J mice were treated for 9 weeks with ethanol (20%, v/v) before SL-CLP was induced. Systolic blood pressure (SBP), survival rate, creatinine plasma, oxidative stress, and inflammatory parameters, inducible nitric oxide synthase (iNOS), cytokines, and metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) levels were evaluated. Chronic ethanol consumption increased SBP, plasma creatinine, O2.-, H2O2, lipid peroxidation, catalase activity, Nox4, IL-6, and TNF-α levels, and MMP-9/TIMP-1 ratio. SL-CLP decreased SBP, increased creatinine, lipid peroxidation, IL-6, TNF-α, nitrate/nitrite (NOx), and iNOS levels, and MMP-2/TIMP-2 ratio, and decreased catalase activity. SL-CLP mice previously treated with ethanol showed a similar decrease in SBP but higher mortality and creatinine levels than SL-CLP alone. These responses were mediated by increased O2-, lipid peroxidation, IL-6, TNF-α, NOx, iNOS, MMP-2, and MMP-9 levels, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios. Our findings demonstrated that previous oxidative stress and inflammatory damage caused by ethanol consumption sensitizes the kidney to SL-CLP injury, resulting in impaired kidney function and sepsis prognosis.