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.

Early combination treatment with existing HIV antivirals: an effective treatment for COVID-19?

OBJECTIVE: Since no effective therapy exists, we aimed to test existing HIV antivirals for combination treatment of Coronavirus disease 19 (COVID-19). MATERIALS AND METHODS: The crystal structures of SARS-CoV-2 main protein (Mpro) (PDB ID: 6Y2F) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (PDB ID: 7BV2) both available from Protein Data Bank were used in the study. Automated Docking by using blind and standard method both on Mpro and RdRp bound to the modified template-primer RNA was performed with AutoDock 4.2.6 program suite. Lamarckian genetic algorithm (LGA) was used for structures docking. All inhibitors were docked with all bonds completely free to rotate. RESULTS: Our molecular docking findings suggest that lopinavir, ritonavir, darunavir, and atazanavir activated interactions with the key binding sites of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) protease with a better inhibition constant (Ki) for lopinavir, ritonavir, and darunavir. Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions. In principle, the four antiviral nucleotides might be used effectively against SARS-CoV-2. CONCLUSIONS: The combination of a protease inhibitor and two nucleoside analogues, drugs widely used to treat HIV infection, could be evaluated in clinical trials for the treatment of COVID-19.

Complex trauma, PTSD and complex PTSD in African refugees.

Background: The introduction of the diagnosis of complex posttraumatic stress disorder (CPTSD) by ICD-11 is a turning point in the field of traumatic stress studies. It's therefore important to examine the validity of CPTSD in refugee groups exposed to complex trauma (CT) defined as a repeated, prolonged, interpersonal traumatic event. Objective: The objective of this study was to compare DSM-5 and ICD-11 post-traumatic stress disorder diagnoses and to evaluate the discriminant validity of ICD-11 PTSD and CPTSD constructs in a sample of treatment-seeking refugees living in Italy. Method: The study sample included 120 treatment-seeking African refugees living in Italy. All participants were survivors of at least one CT. PTSD and CPTSD diagnoses were assessed according to both DSM-5 and ICD-11 criteria. Results: Findings revealed that 79% of the participants met the DSM-5 criteria for PTSD, 38% for ICD-11 PTSD and 30% for ICD-11 CPTSD. Generally, ICD-11 CPTSD items evidenced strong sensitivity and negative predictive power, low specificity and positive predictive power. Latent class analysis results identified two distinct groups: (1) a PTSD class, (2) a CPTSD class. None of the demographic and trauma-related variables analysed was significantly associated with diagnostic group. On the other hand, the months spent in Italy were significantly associated with PCL-5 score. Conclusions: Findings extend the current evidence base to support the discriminant validity of PTSD and CPTSD amongst refugees exposed to torture and other gross violations of human rights. The results suggest also that, in the post-traumatic phase, the time spent in a 'safe place' condition contributes to improve the severity of post-traumatic symptomatology, but neither this variable nor other socio-demographic factors seem to contribute to the emergence of complex PTSD. Further investigations are needed to clarify which specific vulnerability factors influence the development of PTSD or CPTSD in refugees exposed to complex trauma.

Antecedentes: La introducción del diagnóstico del trastorno de estrés postraumático complejo (TEPT-C) por la CIE-11 es un punto de inflexión en el campo de los estudios del estrés traumático. Por lo tanto, es importante examinar la validez del TEPT-C en los grupos de refugiados expuestos a un trauma complejo (TC) definido como un evento traumático interpersonal prolongado y repetido.Objetivo: El objetivo de este estudio fue comparar los diagnósticos de trastorno de estrés postraumático del DSM-5 y la CIE-11 y evaluar la validez discriminante de los constructos del TEPT y TEPT-C de la CIE-11 en una muestra de refugiados en busca de tratamiento que viven en Italia.Método: La muestra del estudio incluyó a 120 refugiados africanos que buscan tratamiento y que viven en Italia. Todos los participantes fueron sobrevivientes de al menos un TC. Los diagnósticos de TEPT y TEPT-C se evaluaron de acuerdo con los criterios del DSM-5 y de la CIE-11.Resultados: Los hallazgos muestran que el 79% de los participantes cumplieron con los criterios del DSM-5 para el TEPT, el 38% para el TEPT de la CIE-11 y el 30% para el TEPT-C de la CIE-11. En general, los ítems de TEPT-C de la CIE-11 evidenciaron una fuerte sensibilidad y poder predictivo negativo, baja especificidad y poder predictivo positivo. Los resultados del análisis de clase latente identificaron dos grupos distintos: (1) grupo de TEPT, (2) grupo de TEPT-C. Ninguna de las variables demográficas y relacionadas con el trauma analizadas se asoció significativamente con el grupo de diagnóstico. Por otro lado, los meses pasados en Italia se asociaron significativamente con la puntuación de PCL-5.Conclusiones: Los hallazgos amplían la base de evidencia actual para apoyar la validez discriminante del TEPT y el TEPT-C entre los refugiados expuestos a tortura y otras violaciones graves de los derechos humanos. Los resultados sugieren también que, en la fase postraumática, el tiempo pasado en una condición de "lugar seguro" contribuye a mejorar la gravedad de la sintomatología postraumática, pero ni esta variable ni otros factores sociodemográficos parecen contribuir a la aparición del TEPT-C. Se necesitan más investigaciones para aclarar qué factores de vulnerabilidad específicos influyen en el desarrollo de TEPT o TEPT-C en los refugiados expuestos a trauma complejo.

Sportomics: metabolomics applied to sports. The new revolution?

Sportomics is the application of metabolomics in sports to investigate the metabolic effects of physical exercise on individuals, whether they are professional athletes or not. Metabolomics is one of the "omics" sciences that provide a picture of the metabolic state of a person in physiological or pathological conditions. This is achieved through the analysis of metabolites present in a biological fluid, such as saliva, blood, feces, and urine. The authors revised the recent literature concerning this topic and discussed the useful information that sportomics can provide and the limits of the current experimental settings. Furthermore, in the future, sportomics analyses could be used to prevent and manage injuries as it would be known in advance if an athlete is more prone to experience muscular damage or fatigue. Following more trials, it would also be possible to set the best diet and training programs to get the best performances out of the athletes. Moreover, based on their metabolic profiles, both adults and children could choose tailored physical training in order to preserve and improve their health.

An Innovative Approach to Control Steel Reinforcement Corrosion by Self-Healing.

The corrosion of reinforced steel, and subsequent reinforced concrete degradation, is a major concern for infrastructure durability. New materials with specific, tailor-made properties or the establishment of optimum construction regimes are among the many approaches to improving civil structure performance. Ideally, novel materials would carry self-repairing or self-healing capacities, triggered in the event of detrimental influence and/or damage. Controlling or altering a material's behavior at the nano-level would result in traditional materials with radically enhanced properties. Nevertheless, nanotechnology applications are still rare in construction, and would break new ground in engineering practice. An approach to controlling the corrosion-related degradation of reinforced concrete was designed as a synergetic action of electrochemistry, cement chemistry and nanotechnology. This contribution presents the concept of the approach, namely to simultaneously achieve steel corrosion resistance and improved bulk matrix properties. The technical background and challenges for the application of polymeric nanomaterials in the field are briefly outlined in view of this concept, which has the added value of self-healing. The credibility of the approach is discussed with reference to previously reported outcomes, and is illustrated via the results of the steel electrochemical responses and microscopic evaluations of the discussed materials.

Determination of Chloride Content in Cementitious Materials: From Fundamental Aspects to Application of Ag/AgCl Chloride Sensors.

This paper reports on the advantages and drawbacks of available test methods for the determination of chloride content in cementitious materials in general, and the application of Ag/AgCl chloride sensors in particular. The main factors that affect the reliability of a chloride sensor are presented. The thermodynamic behaviour of silver in the presence or absence of chloride ions is described and kinetic restrictions are addressed. The parameters that can affect the activity of chloride ions in the medium and/or the rate of ion exchange and dissolution/precipitation processes at the sensor's surface are also considered. In this regard, the contribution of morphology and microstructure of the AgCl layer, binding of chloride ions and the compactness of hydration products around the chloride sensor are highlighted. The important parameters for a reliable sensor's response are discussed and the possible causes of inaccuracies are evaluated.

Effects of iron and copper overload on the human liver: an ultrastructural study.

Iron and copper ions play important roles in many physiological functions of our body, even though the exact mechanisms regulating their absorption, distribution and excretion are not fully understood. Metal-related human pathology may be observed in two different clinical settings: deficiency or overload. The overload in liver cells of both trace elements leads to multiple cellular lesions. Here we report the main pathological changes observed at transmission electron microscopy in the liver of subjects affected by Beta-thalassemia and by Wilson's disease. The hepatic iron overload in beta-thalassemia patients is associated with haemosiderin storage both in Kupffer cells and in the cytoplasm of hepatocytes. Haemosiderin granules are grouped inside voluminous lysosomes, also called siderosomes. Other ultrastructural changes are fat droplets, proliferation of the smooth endoplasmic reticulum and fibrosis. Apoptosis of hepatocytes and infiltration of sinusoids by polymorphonucleates is also detected in beta-thalassemia. Ultrastructural changes in liver biopsies from Wilson's disease patients are characterized by severe mitochondrial changes, associated with an increased number of perossisomes, cytoplasmic lipid droplets and the presence of lipolysosomes, characteristic cytoplasmic bodies formed by lipid vacuoles surrounded by electron-dense lysosomes. In patients affected by Wilson's disease, nuclei are frequently involved, with disorganization of the nucleoplasm and with glycogen inclusions. On the contrary, no significant changes are detected in Kupffer cells. Our data show that iron and copper, even though are both transition metals, are responsible of different pathological changes at ultrastructural level. In particular, copper overload is associated with mitochondrial damage, whereas iron overload only rarely may cause severe mitochondrial changes. These differences underlay the need for further studies in which biochemical analyses should be associated with ultrastructural data, in order to better understand the molecular ways associated with iron- and copper-related pathology at subcellular level.

Myoinositol: a new marker of intrauterine growth restriction?

Inositol is a cyclic sugar alcohol which occurs naturally in a variety of stereoisomers, the most common of which is myo-inositol. Inositol phosphoglycan molecules have been isolated from mammalian tissues and are a major component of the intracellular mediators of insulin action. The fetus with intrauterine growth retardation (IUGR) activates a series of adaptive mechanisms to increase the chances for survival, such as a saving of glucose to ensure nutrition of the vital organs, with a consequent reduction in insulin secretion. It can be hypothesized that the reduced production of fetal insulin leads to an excretion of inositol from the intracellular to the extracellular compartment, with a consequent increase of the metabolite in plasma and urine and a decrease inside the cells. Recently, reports suggesting that the increase in extracellular myo-inositol may be a valid marker of an altered glucose metabolism during fetal development in IUGR have been published.

Ultrasonography and neonatal urinary tract infections.

B-mode ultrasonography and the power-Doppler are methods for studies by images in rapid technological evolution. Their applications and limits in the study of infections of the urinary tract in the neonatal period are pointed out.

Serratia marcescens infections and outbreaks in neonatal intensive care units.

Serratia marcescens is an important cause of hospital-acquired infections, especially in neonatal intensive care units (NICUs). This review analyzes clinical signs, risk factors, biotyping and sources of infection in newborns exhibited by this bacteria as well as the therapy which is commonly used and management. This review examines the reported cases of outbreaks of S. marcescens in NICUs published in pubmed over the last 10 years (key words: Serratia marcescens infections, outbreaks, Neonatal intensive Care Units). This report highlights the different prevention and control strategies employed in order to eradicate Serratia outbreaks in NICUs, including all healthcare procedures such as hand washing, introduction of alcohol-based antiseptic gel, enhanced cleaning and disinfection of medical equipment and wards, use of single-patient medical instruments, cohorting of colonized and infected infants, periodic screening cultures, earliest discharge of the infants.

Changes in urinary PGE2 after ibuprofen treatment in preterm infants with patent ductus arteriosus.

PURPOSE: To investigate changes in urinary PGE(2) after ibuprofen treatment in preterm infants with patent ductus arteriosus (PDA). METHODS: Twenty preterm infants with a hemodynamically significant PDA (gestational age, 28.6 +/- 2.3 weeks) and 20 controls (gestational age, 30.4 +/- 1.5 weeks) were prospectively enrolled at 48-72 h of life. After enrollment, the former underwent conventional ibuprofen-lysine treatment. At 48-72 h (T(0)) and 108-144 h of life (T(1)), urine samples were noninvasively collected in both groups to measure urinary PGE(2) concentrations (enzyme immunoassay method), and renal function was investigated. RESULTS: Urinary PGE(2) decreased significantly both in ibuprofen-treated patients (66.95 +/- 16.78 vs. 27.15 +/- 17.92 pg/mL, P < 0.001) and in controls (71.7 +/- 16.2 vs. 53.2 +/- 18.4 pg/mL, P < 0.001) from T(0) to T(1). However, urinary PGE(2) at T(1) was significantly lower (P < 0.001) in the ibuprofen group compared to the control group. Acute renal failure occurred in three ibuprofen-treated patients (15%). CONCLUSIONS: Ibuprofen markedly reduces (59.4%) urinary PGE(2) and may alter renal function in the newborn.

Ultrasound in developmental dysplasia of the hip: A screening study in Sardinian newborns.

INTRODUCTION: Developmental dysplasia of the hip (DDH) is the most frequent inborn deformity of the locomotor apparatus. Ultrasound screening is frequently used to identify DDH in view of the brevity of the preclinical period during which diagnosis is possible. Appropriate therapeutic intervention during this period can positively affects the evolution of the disorder. METHODS: An unselected population of 1158 Sardinian neonates underwent ultrasound examinations of both hips, and findings were classified according to the method described by Graf. Patients were assessed by means of retrospective analysis to reveal cases of congenital dislocation of the hip joint. All cases were classified and treatment outcomes determined. RESULTS: A total of 145 hips requiring treatment were observed in 122 children. Hip dysplasia and/or dislocation were diagnosed between the ages of 14 days and 3 months. One month after diagnosis ultrasound findings were normal in 94% of the infants with at least one hip classified as type 2a. The remaining 6% were classified as types 2b, 2c, D, and 3. All were treated with abduction splints, and normal hip development was observed after one or two months of treatment. Type 4 hips were referred to an orthopedic surgeon for specialist treatment. CONCLUSIONS: When performed by skilled operators, ultrasonographic techniques are of considerable value in prescribing treatment for DDH. The satisfactory prognosis associated with early treatment of severe congenital dislocation of the hip joint underlines the advisability of scheduling routine hip screening programs to ensure early diagnosis and effective treatment of the disorder.

Osteo-articular infections in newborns: diagnosis and treatment.

Osteoarticular infections, although uncommon, represent a severe condition in neonates. Infections in newborns are largely of an acute nature, transmitted by hematogenous means. The most frequently observed etiological agents are: Staphylococcus aureus, Gram negative and group B Streptococcus spp. In the majority of cases the metaphyses of the long bone are the most commonly implicated sites, although infection may spread to the contiguous epiphysis and joint in neonates. Diagnosis of acute septic arthritis and osteomyelitis may be hindered, especially in neonates, due to the manifestation of less clear-cut characteristic symptoms and signs compared to in children. When osteomyelitis is suspected, imaging techniques used in association with blood and tissue cultures are the most reliable diagnostic tests. Antimicrobial treatment should be administered for 3-4 weeks, initially intravenously, later switching to oral medication. Surgery is indicated to drain acute abscesses or when no improvement is achieved following antibiotic treatment.

Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites.

Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of proinflammatory cytokines, such as interleukin (IL) 1alpha, IL-6, tumor necrosis factor (TNF) alpha and interferon (IFN) gamma, have been proposed as mediators of cancer cachexia. These data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. To elucidate this we studied the relationship between total serum leptin and serum cytokines IL-1alpha, IL-6, TNFalpha as well as the production of leptin and cytokines by peripheral blood mononuclear cells (PBMC) isolated from cancer patients. Sixteen advanced cancer patients (mainly stage IV) with tumors at different sites were included in the study. The serum levels of leptin in cancer patients were significantly lower than those of healthy individuals at all times (7 a.m., noon, 3 p.m.). No significant differences were found in circadian rhythm between patients and controls. Serum levels of IL-1alpha, IL-6, and TNFalpha were significantly higher in cancer patients than in healthy individuals. An inverse correlation between serum levels of leptin and IL-6 was found in cancer patients. The production in culture of leptin by unstimulated PBMCs and those stimulated by phytohemagglutinin M or by phorbol myristate acetate isolated from cancer patients was very low; no differences were observed in comparison with leptin production by PBMCs from healthy individuals.

Relationship between Helicobacter pylori infection and gastric follicular hyperplasia. A retrospective study.

BACKGROUND: The occurrence of lymphoid follicles in the gastric mucosa was recently considered to be acquired in respose to infection by Helicobacter pylori. METHODS: In order to investigate whether there is any correlation between follicular hyperplasia and Helicobacter pylori colonization, a morphological study was performed in antral biopsy specimens from 267 patients with H. pylori-associated gastritis, and from 312 subjects with histological evidence of chronic gastritis, but without H. pylori colonization. RESULTS: Follicular hyperplasia was observed in 33 (12.3%) specimens with H. pylori-associated gastritis, and in 56 (9%) samples from non-infected group (p=ns). In both H. pylori-positive and H. pylori-negative specimens lymphoid follicular hyperplasia showed a significant correlation with the degree of the gastritis. In these two groups the prevalence of follicular hyperplasia was also significantly higher in the elderly. CONCLUSIONS: On the basis of these results, we were unable to find any significant correlation between H. pylori infection and occurrence of lymphoid follicular hyperplasia. The appearance of organized follicular structures in the gastric mucosa seems to be acquired in response to multiple events, and not exclusively in consequence of the colonization by Helicobacter pylori.

[The health and social problems of immigrant children]. / Problematiche sanitarie e sociali dei bambini immigrati.

Assessing both health and human problems of immigrant children, the authors wish them to be included in the social life with no discriminatory attitude, with the rights belonging to any man, in accordance with cultural and religious habits, customs and tradition.

A retrospective study on the incidence of lymphocytic gastritis in patients with Helicobacter pylori infection.

To investigate the relationship between lymphocytic gastritis and H. pylori infection, antral biopsy specimens from 162 patients with histological evidence of H. pylori infection, and from 177 subjects without colonization were retrospectively examined. Among patients with antral colonization, lymphocytic gastritis was identified in 8 cases (4.9%). Lymphocytic gastritis was not detected in specimens without H. pylori infection. Quantitation of the epithelial lymphocytic infiltration was carried out in all specimens and showed that cases with lymphocytic gastritis had a mean of 35.3 lymphocytes per 100 epithelial cells, compared with a mean of 2.6 and 2.4 respectively in chronic gastritis and normal mucosa. Among the 331 patients without lymphocytic gastritis, specimens colonized by H. pylori had a mean of epithelial lymphocyte counts significantly higher than those observed in both chronic gastritis and normal mucosa. These findings show a positive correlation between antral colonization by H. pylori and occurrence of lymphocytic gastritis, and suggest that the bacteria may have an important role in the induction of such particular form of antral inflammation.

Helicobacter pylori in Barrett's esophagus and in normal or inflamed esophageal mucosa: a retrospective study.

To investigate on the presence and significance of Helicobacter pylori (Hp) in Barrett's mucosa, esophageal biopsy specimens from 34 patients with columnar-lined epithelium were retrospectively examined. The incidence of colonization was compared with that observed in a control group of 76 subjects with normal esophageal mucosa or moderate esophagitis. Three of the 34 Barrett's specimens were Hp-positive and only 1 of these showed evidence of inflamed mucosa (p = NS). We do not find in this study any evidence to support the existence of association between Hp and Barrett's esophagus or esophageal inflammation. The presence of Hp in antral mucosa of all positive cases suggest the possibility that esophageal colonisation might merely be a consequence of reflux from the gastric antrum.

EPR investigation of the oxovanadium(IV) complexes formed by the tripeptide glutathione and some related ligands in aqueous solution.

Complex formation between oxovanadium(IV) and glutathione (gamma-L-glutamyl-L-cysteinylglycine, GSH) was investigated in aqueous solution by EPR and electron absorption spectroscopy to identify the complexed species that were reported to form upon reduction of exogenous vanadium(V) in cellular systems. The complexing behavior of the related ligands glycine, N-acetyl-glycine, 3-mercaptopropionic acid, cysteamine, L-cysteine, N-acetyl-L-cysteine, N-acetyl-cysteamine, and oxidized glutathione (GSSG) was also examined in order to have suitable reference models. The results are compared with those reported previously.

Effect of Helicobacter pylori colonization on quantitative distribution of antral G-cells in apparently healthy subjects and in duodenal ulcer patients. A morphometric study.

To investigate whether antral colonization by Helicobacter pylori (Hp) modifies gastrin-cell population, the number of G-cells was evaluated in antral biopsy specimens from 22 apparently healthy subjects and from 48 duodenal ulcer patients using a morphometric method. The level of serum immunoreactive gastrin in a sample of fasting serum obtained at the time of biopsy was also measured. In healthy subjects the G-cell count (evaluated according to G/I index) and the serum gastrin levels were not significantly different than those found in duodenal ulcer patients. When the antral colonization by Hp was assessed, we found that, both controls and duodenal ulcer Hp-positive patients had a mean G-cell count and fasting serum gastrin levels not significantly higher than in patients without Hp.