p38 MAPK and MKP-1 control the glycolytic program via the bifunctional glycolysis regulator PFKFB3 during sepsis.

Hyperlactatemia often occurs in critically ill patients during severe sepsis/septic shock and is a powerful predictor of mortality. Lactate is the end product of glycolysis. While hypoxia due to inadequate oxygen delivery may result in anaerobic glycolysis, sepsis also enhances glycolysis under hyperdynamic circulation with adequate oxygen delivery. However, the molecular mechanisms involved are not fully understood. Mitogen-activated protein kinase (MAPK) families regulate many aspects of the immune response during microbial infections. MAPK phosphatase (MKP)-1 serves as a feedback control mechanism for p38 and JNK MAPK activities via dephosphorylation. Here, we found that mice deficient in Mkp-1 exhibited substantially enhanced expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) 3, a key enzyme that regulates glycolysis following systemic Escherichia coli infection. Enhanced PFKFB3 expression was observed in a variety of tissues and cell types, including hepatocytes, macrophages, and epithelial cells. In bone marrow-derived macrophages, Pfkfb3 was robustly induced by both E. coli and lipopolysaccharide, and Mkp-1 deficiency enhanced PFKFB3 expression with no effect on Pfkfb3 mRNA stability. PFKFB3 induction was correlated with lactate production in both WT and Mkp-1-/- bone marrow-derived macrophage following lipopolysaccharide stimulation. Furthermore, we determined that a PFKFB3 inhibitor markedly attenuated lactate production, highlighting the critical role of PFKFB3 in the glycolysis program. Finally, pharmacological inhibition of p38 MAPK, but not JNK, substantially attenuated PFKFB3 expression and lactate production. Taken together, our studies suggest a critical role of p38 MAPK and MKP-1 in the regulation of glycolysis during sepsis.

Mitogen-activated protein kinase phosphatase-1 controls PD-L1 expression by regulating type I interferon during systemic Escherichia coli infection.

Mitogen-activated protein kinase phosphatase 1 (Mkp-1) KO mice produce elevated cytokines and exhibit increased mortality and bacterial burden following systemic Escherichia coli infection. To understand how Mkp-1 affects immune defense, we analyzed the RNA-Seq datasets previously generated from control and E. coli-infected Mkp-1+/+ and Mkp-1-/- mice. We found that E. coli infection markedly induced programmed death-ligand 1 (PD-L1) expression and that Mkp-1 deficiency further amplified PD-L1 expression. Administration of a PD-L1-neutralizing monoclonal antibody (mAb) to Mkp-1-/- mice increased the mortality of the animals following E. coli infection, although bacterial burden was decreased. In addition, the PD-L1-neutralizing mAb increased serum interferon (IFN)-γ and tumor necrosis factor alpha, as well as lung- and liver-inducible nitric oxide synthase levels, suggesting an enhanced inflammatory response. Interestingly, neutralization of IFN-α/ß receptor 1 blocked PD-L1 induction in Mkp-1-/- mice following E. coli infection. PD-L1 was potently induced in macrophages by E. coli and lipopolysaccharide in vitro, and Mkp-1 deficiency exacerbated PD-L1 induction with little effect on the half-life of PD-L1 mRNA. In contrast, inhibitors of Janus kinase 1/2 and tyrosine kinase 2, as well as the IFN-α/ß receptor 1-neutralizing mAb, markedly attenuated PD-L1 induction. These results suggest that the beneficial effect of type I IFNs in E. coli-infected Mkp-1-/- mice is, at least in part, mediated by Janus kinase/signal transducer and activator of transcription-driven PD-L1 induction. Our studies also support the notion that enhanced PD-L1 expression contributes to the bactericidal defect of Mkp-1-/- mice.

Applications of PET/MRI in Abdominopelvic Oncology.

With PET/MRI, the strengths of PET and MRI are combined to allow simultaneous image acquisition and near-perfect image coregistration. MRI is increasingly being used for staging and restaging of abdominopelvic oncologic lesions, including prostate, hepatobiliary, pancreatic, neuroendocrine, cervical, and rectal cancers. Fluorine 18-fluorodeoxyglucose PET/CT has long been considered a cornerstone of oncologic imaging, and the development of multiple targeted radiotracers has led to increased research on and use of these agents in clinical practice. Thus, simultaneously performed PET/MRI enables the acquisition of complementary imaging information, with distinct advantages over PET/CT and MR image acquisitions. The authors provide an overview of PET/MRI, including descriptions of the major differences between PET/MRI and PET/CT, as well as case examples and treatment protocols for patients with commonly encountered malignancies in the abdomen and pelvis. Online supplemental material is available for this article. ©RSNA, 2021.

Impact of self-ligating orthodontic brackets on dental biofilm and periodontal pathogens in adolescents.

The aim of the present prospective study was to evaluate periodontal health and subgingival microbiological alterations in adolescents treated with fixed self ligating orthodontic brackets in comparison to subject without any orthodontic appliance. A total of 40 adolescents (23 females and 17 males; mean age: 13.2 ± 3.2 years) were included: 30 subjects with self ligating brackets (test group) and 10 patients without orthodontic appliances (control group). Follow-ups were as follows: T1 (1 month), T2 (3 months), T3 (6 months) from the beginning of the orthodontic therapy. Clinical parameters (plaque index, gingival index and clinical attachment level) were measured for every patient and a microbiological analysis was performed. Mann Whitney test was performed to evaluate clinical parameters between test and control group and Friedman test and Fisher test were adopted to evaluate intra group differences at different follow-ups. Student T-test was performed to compare clinical attachment level between the two groups. Significance level was set at p<0.05. No periodontal pathogens and no clinical attachment loss were found in the whole sample. A slightly higher plaque index and gingival inflammation were recorded in the test group in comparison to the controls.

Oral manifestations in paediatric patients with hepatobiliary diseases: a review.

It is well known that greenish pigmentation of the teeth is seen in children following remission of severe jaundice and clinical and serum bilirubin, a degradation product of haemoglobin, may be permanently trapped in forming dental hard tissues causing discolouration and enamel and dentine hypoplasia. Neonatal jaundice is the most common cause of hyperbilirubinemia and pigmentation of the deciduous teeth is the consequence of this condition. Various hepatobiliary pathologies may have a clinical finding in the oral cavity; furthermore, oral manifestations of hepatic pathologies are not just limited to the pigmentation of the deciduous teeth but also the permanent dentition and the mucous membranes can be affected.

Impact of Sjögren's syndrome on oral health and quality of life: an observational cross-sectional study.

Sjögren's Syndrome is a complex disease, due to an autoimmune physiopathology, that strongly impacts both patients' primary needs (nutrition and speaking), and patients' relationship life related factors (psychological health and quality of life). In Literature, few studies had investigated oral health status in Sjögren's syndrome and its impact on patients' quality of life, so the aim of this study was to analyse that issue. 30 patients were enrolled, within the Department of Rheumatology (University of Pisa), both first diagnosis patients' and both patients who had been diagnosed with Sjögren's syndrome in the past. For each patient, a medical record was filled out together with the compilation of the Oral Health Impact Profile questionnaire. Then, during a specialistic rheumatologic visit, Sjögren's Syndrome Disease Damage Index Score (SSDDI) was determined. Results showed a direct proportion between years from diagnosis and severity of oral health issues. It was found that these issues were related to soft tissue damage and an overall worse, reported quality of life and psychological health.

Use of extra-oral scanner for the study of arch form in a sample of Italian adolescents with ideal occlusion.

The aim of this study was to evaluate the shape and the average size of the maxillary and mandibular arch in an Italian adolescents' sample with correct occlusion, using the digital technology. The study sample was composed, after the use of an extra-oral scanner and after the application of inclusion and exclusion criteria, by the digitized dental casts of 79 Italian adolescents (39 females and 40 males), aged 14±1 years, with correct occlusion. On each model, both upper and lower, the reference points of the dental arches (FA), of the alveolar bone (WALA ridges) and of the incisal edge of the central incisors were identified. With these points, using a software, fourteen parameters were evaluated for each cast: basal and dental intermolar and inter-canine width, basal and dental molar and canine depth, basal and dental molar and canine ratio, overjet, overbite. Finally, the shape of the arches was assessed, dividing it into ovoid, triangular or square. Chi-square test and Student's T-test for each parameter were adopted with a p<0,05 significance level. The results showed that the ovoid form was the most frequent, followed by the triangular one for the upper arch and by the rectangular one for the lower arch. On the canine level, both upper and lower, both for dental and for basal references, the triangular shape showed the lowest width and ratio values and the highest depth values in comparison with the other two groups. The square one showed the opposite situation, and the ovoid one presented in the intermediate value. On the molar level the trend is quite similar to the canine one. The results obtained maybe suggest that on a significant percentage of the patients of the sample is expected to use a preformed ovoid arch wire, and the data found could be useful to study the adequacy of the arch wires currently on the market or to design new ones. .

Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?

Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.

The role of transesophageal echocardiography in the management of renal cell carcinoma with venous tumor thrombus.

We reviewed the role of transesophageal echocardiography (TEE) in the management of renal cell carcinoma (RCC) with associated tumor thrombus. Many consider intraoperative TEE as imperative in cases of Level 4 thrombi with atrial involvement, as well as in cases that require the use of cardiopulmonary bypass (CPB). However, the role of TEE in the surgical management of RCC with associated inferior vena cava (IVC) thrombus may expand beyond this subset. When performed after induction, TEE provides updated information regarding tumor thrombus staging, which is essential for optimal surgical planning. Furthermore, TEE provides feedback regarding properties of the thrombus, such as fragility and adherence, which may alter surgical technique. TEE can also be used intraoperatively for central venous line placement, to monitor cardiovascular and fluid status, to guide vascular clamp placement, and to ensure complete removal of the tumor thrombus. In some cases, the use of TEE allows for less morbid procedures and safe avoidance of CPB. We therefore recommend the use of preoperative TEE in all cases with a known tumor thrombus with discretion as to what extent TEE is used throughout the remainder of the case. Further investigation is necessary to elucidate the effect of TEE on patient outcomes, including surgical complication rates, morbidity and mortality of procedures, and cancer control.

Frequency of DEA 1 antigen in 1037 mongrel and PUREBREED dogs in ITALY.

BACKGROUND: The prevalence of dog erythrocyte antigen (DEA 1) in canine population is approximately 40-60%. Often data are limited to a small number of breeds and/or dogs. The aims of this study were to evaluate frequency of DEA 1 in a large population of purebred and mongrel dogs including Italian native breeds and to recognize a possible association between DEA 1 and breed, sex, and genetic and phenotypical/functional classifications of breeds. Frequencies of DEA 1 blood group collected from screened/enrolled blood donors and from healthy and sick dogs were retrospectively evaluated. The breed and the sex were recorded when available. DEA 1 blood typing was assessed by immunocromatographic test on K3EDTA blood samples. The prevalence of DEA 1 antigen was statistically related to breed, gender, Fédération Cynologique Internationale (FCI) and genotypic grouping. RESULTS: Sixty-two per cent dogs resulted DEA 1+ and 38% DEA 1-. DEA 1- was statistically associated with Dogo Argentino, Dobermann, German Shepherd, Boxer, Corso dogs, the molossian dogs, the FCI group 1, 2 and 3 and the genetic groups "working dogs" and "mastiff". DEA 1+ was statistically associated with Rottweiler, Briquet Griffon Vendéen, Bernese mountain dog, Golden Retriever, the hunting breeds, the FCI group 4, 6, 7 and 8 and the genetic groups "scent hounds" and "retrievers". No gender association was observed. CONCLUSIONS: Data obtained by this work may be clinically useful to drive blood donor enrollment and selection among different breeds.

Treatment options of periapical cysts of deciduous teeth: report of a case and systematic review of the literature.

AIM: Periapical cysts of primary teeth are pathologic entities which are seldom encountered in the clinical practice. Most frequently, these lesions arise in correspondence with primary teeth presenting previous pulp therapy, severe carious lesions, or a history of previous trauma. The aim of the present study is to systematically review the treatment modalities of periapical cysts of the deciduous, along with the reporting of a clinical case. MATERIALS: A case of periapical cyst treated with marsupialization occurring in an 11-year-old patient is described. A literature search was devised to retrieve studies reporting the treatment of periapical cysts, and involved papers published in the Cochrane Oral Health Group specialist trials, MEDLINE via PubMed, and EMBASE up to March 2023. A total of 39 articles were retrieved. Following title and abstract analysis, 27 articles were selected for full-text analysis, with the final inclusion of 24 articles. CONCLUSION: Periapical cysts of primary teeth present an overall good prognosis irrespective of the treatment option adopted. The performance of a prompt diagnosis appears of utmost importance, as the extraction of the primary teeth involved implies the management of the residual space for the correct positioning of the corresponding permanent teeth.

Early orthodontic treatment need in paediatric age: a prospective observational study in Italian school-children.

AIM: This study evaluates the prevalence of Interceptive Orthodontic Treatment Need (IOTN) in Italian school-children. METHODS: A prospective observational study was conducted to assess the prevalence of IOTN in patients undergoing a first visit at the Santa Chiara Hospital Paediatric Dentistry Unit in Pisa, Italy. Two thousand, one hundred ninetynine subjects met the inclusion criteria and were enrolled in the study; data on age, gender and concomitant systemic pathologies were collected from medical records. All participants were examined for individual IOTN: the presence of anterior and/or unilateral/bilateral crossbite with or without midline deviation, bad habits (finger, sucking habits, mouth breathing, and tongue thrust), overjet > 3 mm, lack of space for 1.2 and 2.2 eruption were investigated. The presence of one of the above mentioned parameters was considered positive for IOTN. Chi-square test was used to evaluate any statistically significant difference (p < 0.05). CONCLUSION: The study confirms the presence of a significant percentage of paediatric patients who need IOTN; early treatment is highly recommended to reduce malocclusion outcomes in the adult population.

Parental attitude toward children's oral health during COVID-19 pandemic: a cross-sectional study in Italy.

AIM: During the COVID-19 pandemic, restrictive rules were imposed around the world to limit the spread of the virus. The present study aims to investigate how the pandemic and the consequent restrictions have affected the lives and oral health of Italian families with children aged 0-14 years. MATERIALS: Through a questionnaire distributed online from December 2020 to March 2021 the following aspects were investigated: family income during the pandemic, fear of the pandemic, dietary habits, perceived risk of infection in a dental practice and perceived children oral health status during the pandemic. CONCLUSION: The pandemic has not drastically changed the socio-economic conditions, the dietary habits and the oral health condition of most Italian children. Nevertheless, the pandemic seems to have highlighted significant macro-regional differences regarding the satisfaction with the response of the regional health services to the pandemic. The continuation of the pandemic and the possible socio-economic effects could favour new changes in lifestyles, oral health and discrepancies regarding health care access, which deserve to be the subject of further investigation.

Open data for assessing habitats degree of conservation at plot level. An example dataset of forest structural attributes in Val d'Agri (Basilicata, Southern Italy).

Forests supply multiple ecosystem services and host a large proportion of the Earth's terrestrial biodiversity. In particular, they provide habitats for many taxonomic groups which can be threatened by forest unsustainable management practices. Type and intensity of forest management are widely recognized as the main drivers of structure and functions in forests ecosystems. However, to better understand the impacts and the benefits deriving from forest management, there is a big need to standardize procedures of field data collection and data analysis. Here, we provide a georeferenced dataset of vertical and horizontal structure of forest types belonging to 4 habitat types, sensu Council Directive 92/43/EEC. The dataset includes structural indicators commonly linked to old-growth forests in Europe, in particular the amount of standing and lying deadwood. We collected data on 32 plots (24 of 225 m2, and 8 of 100 m2, according to different forests type) during spring and summer of 2022, in Val d'Agri (Basilicata, Southern Italy). The dataset we provide follows the common national standard for field data collection in forest habitat types, published by ISPRA in 2016 with the aim to promote a greater homogeneity in assessment of habitat conservation status at Country and biogeographical level, as requested by the Habitats Directive.

Contemporary Review of Multimodality Imaging of the Prostate Gland.

Tissue changes and the enlargement of the prostate, whether benign or malignant, are among the most common groups of diseases that affect men and can have significant impacts on length and quality of life. The prevalence of benign prostatic hyperplasia (BPH) increases significantly with age and affects nearly all men as they grow older. Other than skin cancers, prostate cancer is the most common cancer among men in the United States. Imaging is an essential component in the diagnosis and management of these conditions. Multiple modalities are available for prostate imaging, including several novel imaging modalities that have changed the landscape of prostate imaging in recent years. This review will cover the data relating to commonly used standard-of-care prostate imaging modalities, advances in newer technologies, and newer standards that impact prostate gland imaging.

Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of immune reconstitution inflammatory syndrome or human papillomavirus (HPV)-related oral diseases were found in this study.

Impairment of salivary function in juvenile idiopathic oligoarticular arthritis is a sign of early onset disease.

AIM: Recent evidences of the presence of reduced stimulated salivary flow rate and altered saliva composition in oligoarticular juvenile idiopathic arthritis (o-JIA) suggest a specific damage to the salivary glands. The aim of this cross-sectional study was to investigate whether reduced salivary flow rate could be related to age and gender at disease onset in o-JIA. METHODS: A total of 57 Caucasian patients (41 females and 16 males) aged 5 to 16 years affected by o-JIA were consecutively enrolled in the study. Information on medication intake, dietary and oral hygiene habits were gathered through a standardised questionnaire. All patients underwent oral and sialometry examination. CONCLUSION: Early onset disease would seem to be associated with salivary glands impairment. Regular dental and salivary gland function assessments may be highly recommended in o-JIA patients considering that saliva collection is a non-invasive and inexpensive procedure.

Age, gender and degree of inclusion are predictors of timing for spontaneous repositioning of intruded primary teeth in pre-school children.

AIM: To investigate the timing for spontaneous repositioning of primary teeth with intrusive luxation in relation to degree of inclusion, gender and age of injured children. METHODS: This retrospective study analysed records of 1- to 6-year-old children referred to the Section of Paediatric Dentistry, C.I.R. Dental School, University of Turin (Italy) between January 2009 and December 2020 for traumatic intrusion of primary teeth. Time to the total re-eruption was calculated, and related factors were explored using Cox and Kaplan-Meier analyses. CONCLUSION: Timing for spontaneous re-eruption seems to be associated to age, particularly as far as total intrusion of primary teeth is concerned. This observation could be related to the degree of bone mineralisation, which is modified during growth.

Mechanics of facial growth in young patients.

AIM: The aim of this work is to focus on the impact of occlusion on facial development. METHODS: Literature was searched using Medline, Embase and Cochrane Library. The key words and mesh used were bone remodelling, facial growth, masticatory muscles, children. Only articles written in English were included in the study. CONCLUSION: Disturbances in the harmonious interplay of the masticatory muscles may result in facial alteration and asymmetries. If not treated, the dysplastic pattern of growth continues and worsens with time.