JNK Activation Correlates with Cognitive Impairment and Alteration of the Post-Synaptic Element in the 5xFAD AD Mouse Model

The c-Jun N-terminal kinases (JNKs) are a family of proteins that, once activated by stress stimuli, can alter neuronal functions and survival. The JNK cascade plays a crucial role in the post-synaptic neuronal compartment by altering its structural organization and leading, at worst, to an overall impairment of neuronal communication. Increasing evidence suggests that synaptic impairment is the first neurodegenerative event in Alzheimer’s disease (AD). To better elucidate this mechanism, we longitudinally studied 5xFAD mice at three selected time points representative of human AD symptom progression. We tested the mice cognitive performance by using the radial arm water maze (RAWM) in parallel with biochemical evaluations of post-synaptic enriched protein fraction and total cortical parenchyma. We found that 5xFAD mice presented a strong JNK activation at 3.5 months of age in the post-synaptic enriched protein fraction. This JNK activation correlates with a structural alteration of the post-synaptic density area and with memory impairment at this early stage of the disease that progressively declines to cause cell death. These findings pave the way for future studies on JNK as a key player in early neurodegeneration and as an important therapeutic target for the development of new compounds able to tackle synaptic impairment in the early phase of AD pathology

GOOD OUTCOME FOR VERY HIGH RISK ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA CARRYING GENETIC ABNORMALITIES t(4;11)(q21;q23) or t(9;22)(q34;q11), IF PROMPTLY SUBMITTED TO ALLOGENEIC TRANSPLANTATION, AFTER OBTAINING A GOOD MOLECULAR REMISSION.

Background and Objectives: Acute lymphoblastic leukaemia (ALL) carrying t(9;22) or t(4;11) genetic abnormalities represents a very high risk subtype of disease (VHR-ALL). Hematopoietic stem cell transplantation (HSCT) still remains the only curative option also in the Imatinib era. In the last years low molecular level of minimal residual disease (MRD) before HSCT was reported as one of the best favourable indexes for survival in ALL. Here we observed that even these patients can show a favourable outcome, if submitted to HSCT with very low MRD. Methods: We considered 18 consecutive VHR-ALL patients eligible to HSCT. 16 of them were transplanted upon first remission, as soon as possible, employing myelo-ablative conditioning regimens. Molecular MRD has been evaluated before and after HSCT.Results: Immediately before HSCT MRD revealed: complete molecular remission (MRDneg) for 5 patients and a level <1x10-3 for 7 patients; 100 days after HSCT we had: MRDneg for 7 patients and a decrease for all the others after HSCT. After tapering of immunosuppressive drugs, 13 patients reached the MRDneg in a median time of 8 months (range 3-16); Based on intention to treat analysis: 14/18 patients are alive and disease free at the time of analysis, overall survival and event free survival is of 78% and 66% respectively, with an average follow-up of 45 months (range 6-84) since HSCT. Conclusion: Early transplantation with low MRD level seems to be correlated with a favourable outcome also in VHR-AL

Assessment of Oral Microbiome Changes in Healthy and COVID-19-Affected Pregnant Women: A Narrative Review

During pregnancy, there are several metabolic changes and an alteration in the composition of microorganisms that inhabit the oral cavity, with an increase in pathogenic bacteria that promote the onset of gingival diseases. This review is based on research in reference to the PICO model (Problem/Intervention/Comparison/Outcome), related to changes in the oral microbiome of pregnant women and possible oral consequences in patients with COVID-19. The results showed a growth of some pathogenic bacteria in pregnant women, including Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, and the selective growth of the Prevotella intermedia, Porphyromonas gingivalis and Tannerella species, probably due to the fact that these bacteria use progesterone as a source of nutrition. These same bacteria are implicated in the development of periodontal disease. Periodontal pockets have bidirectional interactions between the oral cavity and the systemic circulatory system through the peripheral gingival blood vessels. The affinity of the SARS-CoV-2 virus to specific membrane receptors is now clear, and could involve the internal and external epithelial lining or the fibroblasts of the periodontal ligament. According to the results of the present review, the control of oral microbiome changes during pregnancy would be welcomed. The use of probiotics could help clinicians manage pregnant patients, reducing inflammatory indexes. Future studies should focus not only on changes in the level of the oral microbiome in pregnancy or the correlation between periodontal disease and COVID-19, but also on oral changes induced by both clinical situations

Assessment of Oral Microbiome Changes in Healthy and COVID-19-Affected Pregnant Women: A Narrative Review

During pregnancy, there are several metabolic changes and an alteration in the composition of microorganisms that inhabit the oral cavity, with an increase in pathogenic bacteria that promote the onset of gingival diseases. This review is based on research in reference to the PICO model (Problem/Intervention/Comparison/Outcome), related to changes in the oral microbiome of pregnant women and possible oral consequences in patients with COVID-19. The results showed a growth of some pathogenic bacteria in pregnant women, including Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, and the selective growth of the Prevotella intermedia, Porphyromonas gingivalis and Tannerella species, probably due to the fact that these bacteria use progesterone as a source of nutrition. These same bacteria are implicated in the development of periodontal disease. Periodontal pockets have bidirectional interactions between the oral cavity and the systemic circulatory system through the peripheral gingival blood vessels. The affinity of the SARS-CoV-2 virus to specific membrane receptors is now clear, and could involve the internal and external epithelial lining or the fibroblasts of the periodontal ligament. According to the results of the present review, the control of oral microbiome changes during pregnancy would be welcomed. The use of probiotics could help clinicians manage pregnant patients, reducing inflammatory indexes. Future studies should focus not only on changes in the level of the oral microbiome in pregnancy or the correlation between periodontal disease and COVID-19, but also on oral changes induced by both clinical situations

Assessment of Genetical, Pre, Peri and Post Natal Risk Factors of Deciduous Molar Hypomineralization (DMH), Hypomineralized Second Primary Molar (HSPM) and Molar Incisor Hypomineralization (MIH): A Narrative Review

Objectives: Analyze defects in the state of maturation of the enamel result in an adequate volume of enamel, but in an insufficient mineralization, which can affect both deciduous teeth and permanent teeth. Among the most common defects, we recognize Deciduous Molar Hypominerlization (DMH), Hypomineralized Second Primary Molar (HSPM), and Molar Incisor Hypomineralization (MIH). These, in fact, affect the first deciduous molars, the second deciduous molars and molars, and permanent incisors, respectively, but their etiology remains unclear. The objective of the paper is to review studies that focus on investigating possible associations between genetic factors or prenatal, perinatal, and postnatal causes and these enamel defects. Materials and methods: A comprehensive and bibliometric search for publications until January 2021 was conducted. The research question was formulated following the Population, Intervention, Comparison, Outcome strategy. Case-control, cross-sectional, cohort studies, and clinical trials investigating genetic and environmental etiological factors of enamel defects were included. Results: Twenty-five articles are included. For genetic factors, there is a statistical relevance for SNPs expressed in the secretion or maturation stage of amelogenesis (16% of studies and 80% of studies that investigated these factors). For prenatal, perinatal, and postnatal causes, there is a statistical relevance for postnatal factors, such as the breastfeeding period (2%), asthma (16%), high fever episodes (20%), infections/illnesses (20%), chickenpox (12%), antibiotic intake (8%), diarrhea (4%), and pneumonia (4%). Conclusions: The results are in agreement with the multifactorial idea of the dental enamel defects etiology, but to prove this, further studies enrolling larger, well-diagnosed, and different ethnic populations are necessary to expand the investigation of the genetic and environmental factors that might influence the occurrence of DMH, HPSM, and MIH

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services