The effect of single and repeated tDCS sessions on motor symptoms in Parkinson's disease: a systematic review.

OBJECTIVES: to update understanding of the effectiveness of transcranial direct current stimulation (tDCS) on motor dysfunction in Parkinson's disease, since the last review was published in 2016. METHODS: in order to identify suitable publications for inclusion, an online search of the Pubmed, Scopus and Cochrane databases was carried out. Searches of relevant full-text articles were performed through specific keywords. The final database check was performed in July 2019. Papers were restricted to studies investigating motor rehabilitative effects of tDCS in adult patients with Parkinson's disease. Studies involving either single or repeated tDCS sessions with a sham or controlled trial type design (which incorporated outcomes on motor performance measures) were considered. As studies varied widely in terms of methodology, a qualitative analysis of the selected studies was performed using the Newcastle-Ottawa Quality Assessment Scale or the Delphi list (depending on the study design). RESULTS: twenty-nine studies were retained in this systematic review. Of the studies included, fifteen involved single tDCS session (patients = 256) and fourteen involved repeated tDCS sessions (patients = 294). Eight investigations of single tDCS and ten investigations of repeated tDCS demonstrated significant results. Studies involving multi- target stimulation demonstrated significant improvements on mobility (p=0.006), balance (by 50.9%), gait velocity (by 29%), fall reduction (p0.05) compared to mono-target stimulations. CONCLUSIONS: despite increasing evidence that tDCS may improve motor symptoms, the results showed that fully optimized tDCS protocols are not yet established.

Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients.

Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.

Brucella suis infection in domestic pigs in Sardinia (Italy).

During a 4-year (2007-2010) survey, the presence of Brucella suis infection in domestic pigs in Sardinia was investigated. Serum samples were collected from breeding pigs located on 108 commercial farms with documented reproductive problems and analysed using the Rose Bengal (RBT) and complement fixation (CFT) tests for screening and confirmation of Brucella, respectively. Of the 1251 serum samples analysed by RBT, 406 sera, originating from 36 farms, were positive for B. suis. CFT was positive in 292/748 sera analysed, confirming positivity in all 36 pig herds. Pigs with international complement fixation test units per ml (ICFTU/ml) values ⩾160 were slaughtered, and their organs collected for bacteriological examination and testing by polymerase chain reaction (PCR). Brucella spp. strains were isolated in culture from 13/502 organs analysed, and subsequently identified as B. suis biovar 2. PCR detected positivity to Brucella spp. in 19/285 organs analysed. These results confirm the presence and emergence of B. suis infection in domestic pigs in Sardinia.

Oral-Gut-Estrobolome Axis May Exert a Selective Impact on Oral Cancer.

A subset of bacterial species that holds genes encoding for ß-glucuronidase and ß-galactosidase, enzymes involved in the metabolism of conjugated estrogens, is called the "estrobolome." There is an emerging interest embracing this concept, as it may exert a selective impact on a number of pathologies, including oral cancer. Although the estrobolome bacteria are typically part of the gut microbiota, recent experimental pieces of evidence have suggested a crosstalk among oral and gut microbiota. In fact, several oral bacterial species are well represented also in the gut microbiota, and these microbes can effectively induce the estrobolome activation. The main pathways used for activating the estrobolome are based on the induction of the expression patterns for 2 bacterial enzymes: ß-glucuronidase and aromatase, both involved in the increase of estrogen released in the bloodstream and consequently in the salivary compartment. Mechanistically, high estrogen availability in saliva is responsible for an increase in oral cancer risk for different reasons: briefly, 1) estrogens directly exert biological and metabolic effects on oral mucosa cells; 2) they can modulate the pathological profile of some bacteria, somewhere associated with neoplastic processes (i.e., Fusobacterium spp., Parvimonas ssp.); and 3) some oral bacteria are able to convert estrogens into carcinogenic metabolites, such as 4-hydroxyestrone and 16α-hydroxyestrone (16α-OHE), and can also promote local and systemic inflammation. Nowadays, only a small number of scientific studies have taken into consideration the potential correlations among oral dysbiosis, alterations of the gut estrobolome, and some hormone-dependent cancers: this lack of attention on such a promising topic could be a bias affecting the full understanding of the pathogenesis of several estrogen-related oral pathologies. In our article, we have speculated on the activity of an oral-gut-estrobolome axis, capable of synergizing these 2 important microbiotas, shedding light on a pilot hypothesis requiring further research.

Comparing the responses of countries and National Health Systems to the COVID-19 pandemic: a critical analysis with a case-report series.

This review aimed to compare the different responses of countries to the pandemic, their National Health Systems, and their impact on citizens' health. This work aimed to create a narrative plot that connects different discussion points and suggests organizational solutions and strategic choices in the face of the pandemic. In particular, this work focused on public health organizations, specifically the European Union and vaccination politics. It is also based on a case report series (about the United States, Germany, Vietnam, New Zealand, Cuba, and Italy), where each country has responded differently to the pandemic in terms of political decisions such as vaccination type, information to citizens, dealings with independent experts, and other specific country factors. In comparing the various models of care systems response to the pandemic, it emerges that: we have found some (few) good practices, but without global coordination, and this is obviously not enough. It is now quite clear that there cannot be a "good answer" in a single nation. Uncoordinated local responses cannot counter a global phenomenon. The second point is that the general context must be considered from a strategic point of view. With the threat of new pandemics (but also of health disasters linked to climate change, pollution, and wars), humanity finds itself at the crossroads between investing in a "democratic" management of international bodies but without power (and at the mercy of the need for funds with consequent conflicts) or in some new leadership proposals that advocate efficiency and problem-solving (and that would probably be able to implement it) but that would place processes totally outside of the public's control.

Human breast milk cells are positive for the pioneer transcription factor ISL1.

OBJECTIVE: ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. MATERIALS AND METHODS: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep® processor (Hologic® Inc.) in commercial Cytological ThinPrep® solution (Hologic® Inc.), followed by standard immunohistochemical staining of ISL1. RESULTS: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. CONCLUSIONS: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events.

The human carotid atherosclerotic plaque: an observational review of histological scoring systems.

OBJECTIVE: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS: A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events.

Curcumin/H2O2 photodynamically activated: an antimicrobial time-response assessment against an MDR strain of Candida albicans.

OBJECTIVE: Human candidiasis is typically treated with antifungal drugs, but the rise of drug-resistant strains of Candida spp. poses a serious problem, making treatment difficult. At the same time, photodynamic therapy (PDT) has drawn increasing attention from researchers for its potential to effectively inhibit multidrug-resistant pathogenic fungi and for its low tendency to induce drug resistance. This study's goal was to examine how a multidrug-resistant oral isolate of Candida albicans responded to a PDT that used a curcumin/H202 formulation as a photosensitizer and was exposed to various light sources. MATERIALS AND METHODS: A commercial product containing curcumin/H2O2 3% was used as a photosensitizer and evaluated in a PDT treatment that can use two different light sources: traditional irradiation with 7 W light at λ = 460 nm or a new, never evaluated, polarized light source of 25 W with a wavelength range of λ = 380-3,400 nm. The antimicrobial activity of these procedures was assessed on a clinical oral isolate of Candida albicans, in terms of agar susceptibility test, growth curve behavior, and biofilm inhibition. RESULTS: Both light sources were able to activate the photosensitizer formulation, suggesting a fungistatic activity vs. this C. albicans MDR strain. An interesting difference was observed in the cell-generation-time (CGTOD) after PDT treatment, where the polarized light was more active compared to the source of 460 nm. In fact, CGTOD was 16 and 8 hours, respectively. CONCLUSIONS: The PDT evaluated here presented an inhibition window time, a crucial point for clinicians, who could activate an additional prophylactic treatment to resolve the clinical management of Candida infections in the oral cavity.

Strong ACE-2 expression in the choroidal vessels: do high choroid plexuses serve as a gateway for SARS-CoV-2 infection on the human brain?

OBJECTIVE: Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2.  The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses. PATIENTS AND METHODS: Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution. RESULTS: We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a  strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries. CONCLUSIONS: Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells.

Acyl-CoA binding protein (ACBP) is highly expressed in the developing human kidney.

OBJECTIVE: Acyl-CoA-binding protein (ACBP), also known as diazepam binding inhibitor (DBI), is a small phylogenetically conserved protein. This ancestral peptide is multifunctional, performing intracellular activities as ACBP protein or extracellular roles as DBI. Several studies showed its endless facets, including a relevant activity as appetite stimulator and as anabolic factor. High levels of ACBP have been described in erythrocytes, liver, kidney, and gut cells. The aim of this study was to analyze, at immunohistochemical level, the expression of ACBP in fetal human tissues during development, focusing on the developing kidney. MATERIALS AND METHODS: Immunohistochemistry for ACBP was performed on 30 human fetal kidneys, from 15 fetuses of gestational age ranging from 13 to 19 weeks. At autopsy, all kidney samples were 10% formalin-fixed, routinely processed and paraffin-embedded. Five micron-thick paraffin sections were stained with Hematoxylin and Eosin and PAS stain for a morphological examination. RESULTS: ACBP was detected in all 30 kidneys analyzed in this study. No significant changes in ACBP expression were observed at different gestational ages. Immunostaining for ACBP was restricted to the epithelium covering the renal pelvis, the papillae, the collecting tubules, and the proximal and distal tubules. On the other hand, medullary regions and in the metanephric mesenchymal stem/progenitor cells did not show any reactivity for ACBP. CONCLUSIONS: According to our findings, ACBP should be considered as a new player in the complex field of human nephrogenesis, given that it was detected in all fetal kidneys immunostained. Its preferential localization in the renal structures derived from the Wolf duct, such as pelvis epithelium and collecting ducts, suggests a major role for ACBP in the induction of the metanephric mesenchymal cells toward the differentiation into glomerular structures. ACBP expression in proximal and distal tubules, two structures originating from the metanephric mesenchyme, indicates a further role of this protein in nephron development. In conclusion, ACBP should be added to the multiple molecules involved in human nephrogenesis.

Interindividual variability in L1CAM expression in the human kidney during development: are there implications for fetal programming of kidney diseases presenting in adulthood?

OBJECTIVE: L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin superfamily of cell adhesion molecules. The present study investigated the expression of L1CAM during the development in the fetal human kidney at different gestational ages, to reach a better knowledge on the role of L1CAM in renal morphogenesis. MATERIALS AND METHODS: The immunohistochemical analysis for L1CAM was performed in 24 fetal kidneys of different gestational ages, ranging from 10 to 38 weeks. L1CAM expression was observed in all 24 kidneys examined. RESULTS: Immunoreactivity for L1CAM was restricted to the collecting tubules, of the developing fetal kidneys. Moreover, L1CAM was detected in the ureteric bud tips, near the subcapsular metanephric mesenchymal stem/progenitor cells. L1CAM was also expressed in the collecting tubules undergoing fusion with the distal tubules of the developing nephrons. L1CAM was mainly expressed along the cell membrane. In fetal kidneys in which the renal pelvis was observed, epithelial cells of the renal pelvis showed strong membranous reactivity for L1CAM. CONCLUSIONS: Our study shows that L1CAM is expressed in all stages of human kidney nephrogenesis, being restricted to the renal structures derived from the ureteric bud. The expression of L1CAM in the cells of the ureteric bud tips suggests a major role for this adhesion molecule in the induction of metanephric mesenchymal cells to undergo mesenchymal-to-epithelial transition and differentiation into new nephrons. The interindividual variability in L1CAM expression observed in this study might be related to different levels of nephrogenesis, suggesting L1CAM involvement in the fetal programming of adult kidney diseases.

CD44 is highly expressed in stem/progenitor cells originating the intervertebral discs in the human notochord.

OBJECTIVE: The notochord acts as a patterning structure, playing a key role in the formation of the vertebral column, both indirectly by inducing sclerotome cell differentiation and directly by forming the nucleus pulposus of intervertebral discs. The abnormal development of the notochord results in an easy equation with a variety of birth defects. Therefore, we focused our attention on the analysis of the early stages of human notochord development by highlighting the role of progenitor stem cells involved in the origin of intervertebral discs (IVDs). MATERIALS AND METHODS: Eight human fetuses, ranging from 8 up to 21 weeks of gestational age, were obtained from spontaneous abortion or voluntary interruption of gestation. Samples were 10% formalin-fixed, routinely processed, and paraffin-embedded. Five micron-tick paraffin sections were obtained from each sample. Sections were stained with hematoxylin-eosin and PAS stain for a morphological examination. Tissue samples were immunostained with a commercial anti-human CD44 rabbit monoclonal antibody at 1:100 dilution. RESULTS: Immunoreactivity for CD44 was detected in six out of eight notochords examined in this study. Reactivity for CD44 was restricted to progenitor cells giving rise to the nucleus pulposus (NP) of the developing IVDs. Positive cells showed a membranous and/or cytoplasmic immunostaining, no reactivity was observed in the nuclear compartment. CD44 expression was always restricted to IVD precursor cells, whereas cartilage precursors were devoid of labelling. CONCLUSIONS: Our study shows, for the first time, that the stem cell marker CD44 selectively marks intervertebral disc progenitor cells, paralleling their differentiation toward a discogenic phenotype. Therefore, our results suggest that CD44 plays a key role in IVD development, allowing its differentiation from surrounding undifferentiated notochordal cells toward a IVD phenotype. Given the role of CD44 in IVD development, we may hypothesize that low CD44 levels might be associated with changes in IVD development and with susceptibility to develop back pain later in life.

Expression of L1 Cell Adhesion Molecule (L1CAM) in extracellular vesicles in the human spinal cord during development.

OBJECTIVE: L1  cell adhesion molecule (L1CAM) is a glycoprotein characterized by three components: an extracellular region, a transmembrane segment, and a cytoplasmic tail. L1CAM is expressed in multiple human cells, including neurons. The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. The presence of L1CAM on the surface of nerve cells allows the adhesion of neurons among them. Furthermore, when it is bound to itself or to other proteins, L1-CAM induces signals inside the cell. The aim of this work was to study L1CAM expression in the human spinal cord during development, at different gestational ages, through immunohistochemistry. MATERIALS AND METHODS: Immunohistochemical analysis for L1CAM was performed in five human spinal cord samples, including three embryos and two fetuses of different gestational ages, ranging from 8 to 12 weeks. RESULTS: L1CAM expression was detected in all 5 spinal cords examined in this study. The adhesion molecule was found in the vast majority of cells. The highest levels of immunoreactivity for L1CAM were detected at the periphery of the developing organs, in the spinal cord zones occupied by sensory and motor fibers. In the alar and basal columns, immunoreactivity for L1CAM was characterized by a reticular pattern, being mainly expressed in axons. Strong reactivity of L1CAM was also found in extracellular vesicles. This extracellular localization might indicate the ability of L1CAM to mediate the transduction of extracellular signals that support axon outgrowth. CONCLUSIONS: The high reactivity of L1cam in the axons of developing neurons in the fetal spinal cord confirms previous studies on the ability of L1CAM to promote axon sprouting and branching in the developing nervous system. In this work, a new actor is reported to have a role in the complex field of human spinal cord development: L1CAM, whose expression is highly found in the developing neuronal and glial precursors.

The role of fetal programming in human carcinogenesis - May the Barker hypothesis explain interindividual variability in susceptibility to cancer insurgence and progression?

The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.

Ultrastructural findings of lung injury due to Vaccine-induced Immune Thrombotic Thrombo- cytopenia (VITT) following COVID-19 vaccination: a scanning electron microscopic study.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.

Insight into susceptibility genes associated with bipolar disorder: a systematic review.

OBJECTIVE: Bipolar disorder (BD) is a severe disorder, and it is associated with an increased risk of mortality. About 25% of patients with BD have attempted and 11% have died by suicide. All these characteristics suggest that the disorders within the bipolar spectrum are a crucial public health problem. With the development of molecular genetics in recent decades, it was possible to more easily detect risk genes associated with this disorder. This study aimed at summarizing the findings of systematic reviews and meta-analyses on the topic and assessing the quality of the available evidence. MATERIALS AND METHODS: PubMed/Medline and Web of Science were searched to identify systematic reviews and meta-analyses published during 2013-2019. Standard methodology was applied to synthesize and assess the retrieved literature. RESULTS: This systematic review identifies a number of potential risk genes associated with bipolar disorder whose mechanism of action has yet to be confirmed. They are divided into several groups: 1) a list of the most significant susceptibility genetic factors associated with BD; 2) the implication of the ZNF804A gene in BD; 3) the role of genes involved in calcium signaling in BD; 4) DNA methylation in BD; 5) BD and risk suicide genes; 6) susceptibility genes for early-onset BD; 7) candidate genes common to both BD and schizophrenia; 8) genes involved in cognitive status in BD cases; 9) genes involved in structural alteration in BD brain tissue; 10) genes involved in lithium response in BD. CONCLUSIONS: Future research should concentrate on molecular mechanisms by which genetic variants play a major role in BD. Supplemental research is needed to replicate the applicable results.

Fusobacterium nucleatum and alteration of the oral microbiome: from pregnancy to SARS-COV-2 infection.

OBJECTIVE: The human being has evolved in close symbiosis with its own ecological community of commensal, symbiotic and pathogenic bacteria. After the intestinal microbiome, that of the oral cavity is the largest and most diversified. Its importance is reflected not only in local and systemic diseases, but also in pregnancy since it would seem to influence the placental microbiome. MATERIALS AND METHODS: This is a literature review of articles published in PubMed about Fusobacterium Nucleatum and both its implications with systemic and oral health, adverse pregnancy outcomes, flavors perception and its interference in the oral-nasal mucosal immunity. RESULTS: It is in maintaining the microbiome's homeostasis that the Fusobacterium nucleatum, an opportunistic periodontal pathogen of the oral cavity, plays a crucial role both as a bridge microorganism of the tongue biofilm, and in maintaining the balance between the different species in the oral-nasal mucosal immunity also by taste receptors interaction. It is also involved in the flavor perception and its detection in the oral microbiome of children from the first days of life suggests a possible physiological role. However, the dysbiosis can determine its pathogenicity with local and systemic consequences, including the pathogenesis of respiratory infections. CONCLUSIONS: It is interesting to evaluate its possible correlation with Sars-CoV-2 and the consequences on the microflora of the oral cavity, both to promote a possible broad-spectrum preventive action, in favor of all subjects for whom, by promoting the eubiosis of the oral microbiome, a defensive action could be envisaged by the commensals themselves but, above all, for patients with specific comorbidities and therefore already prone to oral dysbiosis.

Sleep/wake rhythm modifications in the Italian population during SARS-CoV2 pandemic: a web-based cross-sectional survey.

OBJECTIVE: The study aims to investigate in a representative sample of the Italian population whether the SARS-CoV2 pandemic and the subsequent home isolation had repercussion on the daily sleep/wake cycling and habits. MATERIALS AND METHODS: A web-based cross-sectional survey consisted of various multiple-choice questions concerning demographic characteristics, sleep habits, and sleep-related problems was broadcast through mainstream social-media. Individuals were randomly allowed to participate from April 29th to May 17th, namely 50 days after the lockdown imposition and the day before its abrogation. RESULTS: 58.84% of respondents experienced a change in their sleep habits. 71% of those whose sleep changed showed a delayed sleep pattern. Overall, a two-fold risk of delayed sleep pattern without any change in total sleep time emerged during the investigation period. Females emerged almost 2 times more likely to modify their sleep habits than males. Youths were also more likely to experience modifications than old people, who conversely appeared protected. A significant improvement in daytime sleepiness occurred during the home isolation which additionally correlated with delayed bedtime and less sleep time. CONCLUSIONS: A high rate of change in sleep habits, especially among youths and females, occurred in Italian population during the home isolation to limit the SARS-CoV2 pandemic. Moreover, self-reported daytime sleepiness decreased in severity.

Heparins and 2019-nCoV infection: a narrative review.

OBJECTIVE: Patients with 2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in preventing thrombotic events in these patients. However, results from clinical studies, so far published, reached controversial conclusions on heparin efficacy in this kind of patients since the incidence of venous thromboembolism remains high despite prophylaxis. This narrative review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARS-CoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis. MATERIALS AND METHODS: We searched for the most relevant published studies on heparins and 2019-nCoV infected patients using the MEDLINE electronic database in the period between January and December 2020. Articles were preliminarily defined as eligible if they: a) were in English language, b) enrolled 250 or more medical ward-patients and 100 or more ICU-patients, c) reported results on patients treated with heparins in a percentage of at least 70% and d) performed an objectively confirmed diagnosis of VTE. RESULTS: Data from medium to large scientific studies show that the incidence of venous thrombotic events in medical ward-patients with SARS-CoV-2 vary between 0% and 8.3%, while this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about 50%. Histological findings show that thrombosis could affect capillaries, main and small-mid-sized vessels, and it is associated with diffuse alveolar damage. CONCLUSIONS: Heparins have anti-inflammatory and anti-viral properties, which may be of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients, could be due to the severity of the disease. Data on the use of heparins in an early phase of the 2019-nCoV infection are still lacking.

Chronic intravascular coagulation in liver cirrhosis predicts a high hemorrhagic risk.

OBJECTIVE: In liver cirrhosis, a complex coagulopathy does exist. The aim was to investigate whether a possible chronic consumption coagulopathy is the underlying phenomenon of the disease. PATIENTS AND METHODS: We measured endogenous thrombin generation with and without thrombomodulin (ETP ratio) along with D-Dimer in a group of consecutive 282 cirrhotic patients. Fibrinogen, Platelet count and the Hemorrhagic score were previously computed in the same patients. The ETP ratio represents the resistance to the anticoagulant activity of TM and should be considered as an index of a procoagulant imbalance. RESULTS: ETP ratio and D-Dimer showed higher values in the cirrhotic patients when compared to controls thus showing a hypercoagulable state. When the patients were divided based on the Hemorrhagic score >7, we found that Fibrinogen, ETP ratio, D-Dimer and the platelet count were significantly different between the two groups. Again, when we considered ETP ratio >0.88, the median value of the cirrhotic patients, all parameters, were statistically different between the two groups. D-Dimer were higher while fibrinogen and platelet count were statistically lower in cirrhotic patients with higher ETP ratio values. Even when the same patients were divided based on their platelet count ( 100 x 109/L) the results showed a similar behavior. ROC curves showed significant AUCs when the hemorrhagic score was challenged against Fibrinogen, D-Dimer, Platelet count and ETP ratio. CONCLUSIONS: In liver cirrhosis hypercoagulable state is associated with an increase in D-Dimer levels along with a decrease in fibrinogen and platelet count thus indicating a low-grade intravascular coagulation which predicts a high hemorrhagic risk.