Modulating the Microbiome for Crohn's Disease Treatment.

The central role of the gut microbiota in the regulation of health and disease has been convincingly demonstrated. Polymicrobial interkingdom interactions between bacterial (the bacteriome) and fungal (the mycobiome) communities of the gut have become a prominent focus for development of potential therapeutic approaches. In addition to polymicrobial interactions, the complex gut ecosystem also mediates interactions between the host and the microbiota. These interactions are complex and bidirectional; microbiota composition can be influenced by host immune response, disease-specific therapeutics, antimicrobial drugs, and overall ecosystems. However, the gut microbiota also influences host immune response to a drug or therapy by potentially transforming the drug's structure and altering bioavailability, activity, or toxicity. This is especially true in cases where the gut microbiota has produced a biofilm. The negative ramifications of biofilm formation include alteration of gut permeability, enhanced antimicrobial resistance, and alteration of host immune response effectiveness. Natural modulation of the gut microbiota, using probiotic and prebiotic approaches, may also be used to affect the host microbiome, a type of "natural" modulation of the host microbiota composition. In this review, we discuss potential bidirectional interactions between microbes and host, and we describe the changes in gut microbiota induced by probiotic and prebiotic approaches as well as their potential clinical consequences, including biofilm formation. We outline a systematic approach to designing probiotics capable of altering the host microbiota in disease states, using Crohn's disease as a model chronic disease. Understanding how the effective changes in the microbiome may enhance treatment efficacy may unlock the possibility of modulating the gut microbiome to improve treatment using a natural approach.

Positive correlational shift between crevicular antimicrobial peptide LL-37, pain and periodontal status following non-surgical periodontal therapy. A pilot study.

BACKGROUND: Periodontitis has a high prevalence and uncertain recurrence. Unlike the pro-inflammatory cytokine profile, little is known about the anti-inflammatory cytokine and antimicrobial peptide overview following treatment. The present study aimed to evaluate if any of the antimicrobial peptide LL-37, interleukin (IL) 4, 10 and 6 together with the volume of gingival crevicular fluid (GCF) and total protein concentration in GCF could be used as correlative biomarkers for the severity in periodontitis as well as prognostic factors in the management of the disease. METHODS: Forty-five participants were recruited and allocated to the healthy (15), Stage I-II (15) or Stage III-IV periodontitis (15) group. Along with periodontal examination, GCF samples were obtained at baseline and 4-6 weeks following scaling and root planing (SRP) for the periodontitis groups. GCF samples were analyzed by ELISA kits to quantify LL-37 and IL-4, -6 and - 10. One-way ANOVA followed by Dunnett's test was used to determine differences among the three groups at baseline. Two-way ANOVA followed by Sidak's post-hoc test was used to compare between pre- and post-SRP in the two periodontitis groups. RESULTS: The amount of GCF volume was significantly correlated to the severity of periodontitis and decreased following SRP, particularly in the Stage III-IV group (p < 0.01). The levels of LL-37, IL-6, and pain and periodontal clinical parameters were significantly correlated to the severity of periodontitis. IL-4 and IL-10 in the periodontitis groups were significantly lower than the healthy group (p < 0.0001) and barely improved following SRP up to the level of the healthy group. CONCLUSIONS: With the limitations of this study, crevicular LL-37 may be a candidate for a biomarker of periodontitis and the associated pain upon probing. TRIAL REGISTRATION: The study was registered in clinical trials.gov, with number NCT04404335, dated 27/05/2020.

Design and Characterization of an RF Applicator for In Vitro Tests of Electromagnetic Hyperthermia.

The evaluation of the biological effects of therapeutic hyperthermia in oncology and the precise quantification of thermal dose, when heating is coupled with radiotherapy or chemotherapy, are active fields of research. The reliable measurement of hyperthermia effects on cells and tissues requires a strong control of the delivered power and of the induced temperature rise. To this aim, we have developed a radiofrequency (RF) electromagnetic applicator operating at 434 MHz, specifically engineered for in vitro tests on 3D cell cultures. The applicator has been designed with the aid of an extensive modelling analysis, which combines electromagnetic and thermal simulations. The heating performance of the built prototype has been validated by means of temperature measurements carried out on tissue-mimicking phantoms and aimed at monitoring both spatial and temporal temperature variations. The experimental results demonstrate the capability of the RF applicator to produce a well-focused heating, with the possibility of modulating the duration of the heating transient and controlling the temperature rise in a specific target region, by simply tuning the effectively supplied power.

Replacing Animal Protein with Soy-Pea Protein in an "American Diet" Controls Murine Crohn Disease-Like Ileitis Regardless of Firmicutes: Bacteroidetes Ratio.

BACKGROUND: The current nutritional composition of the "American diet" (AD; also known as Western diet) has been linked to the increasing incidence of chronic diseases, including inflammatory bowel disease (IBD), namely Crohn disease (CD). OBJECTIVES: This study investigated which of the 3 major macronutrients (protein, fat, carbohydrates) in the AD has the greatest impact on preventing chronic inflammation in experimental IBD mouse models. METHODS: We compared 5 rodent diets designed to mirror the 2011-2012 "What We Eat in America" NHANES. Each diet had 1 macronutrient dietary source replaced. The formulated diets were AD, AD-soy-pea (animal protein replaced by soy + pea protein), AD-CHO ("refined carbohydrate" by polysaccharides), AD-fat [redistribution of the ω-6:ω-3 (n-6:n-3) PUFA ratio; ∼10:1 to 1:1], and AD-mix (all 3 "healthier" macronutrients combined). In 3 separate experiments, 8-wk-old germ-free SAMP1/YitFC mice (SAMP) colonized with human gut microbiota ("hGF-SAMP") from CD or healthy donors were fed an AD, an AD-"modified," or laboratory rodent diet for 24 wk. Two subsequent dextran sodium sulfate-colitis experiments in hGF-SAMP (12-wk-old) and specific-pathogen-free (SPF) C57BL/6 (20-wk-old) mice, and a 6-wk feeding trial in 24-wk-old SPF SAMP were performed. Intestinal inflammation, gut metagenomics, and MS profiles were assessed. RESULTS: The AD-soy-pea diet resulted in lower histology scores [mean ± SD (56.1% ± 20.7% reduction)] in all feeding trials and IBD mouse models than did other diets (P < 0.05). Compared with the AD, the AD-soy-pea correlated with increased abundance in Lactobacillaceae and Leuconostraceae (1.5-4.7 log2 and 3.0-5.1 log2 difference, respectively), glutamine (6.5 ± 0.8 compared with 3.9 ± 0.3 ng/µg stool, P = 0.0005) and butyric acid (4:0; 3.3 ± 0.5 compared with 2.54 ± 0.4 ng/µg stool, P = 0.006) concentrations, and decreased linoleic acid (18:2n-6; 5.4 ± 0.4 compared with 8.6 ± 0.3 ng/µL plasma, P = 0.01). CONCLUSIONS: Replacement of animal protein in an AD by plant-based sources reduced the severity of experimental IBD in all mouse models studied, suggesting that similar, feasible adjustments to the daily human diet could help control/prevent IBD in humans.

IL-33 promotes recovery from acute colitis by inducing miR-320 to stimulate epithelial restitution and repair.

Defective and/or delayed wound healing has been implicated in the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease (IBD). The resolution of inflammation is particularly important in mucosal organs, such as the gut, where restoration of epithelial barrier function is critical to reestablish homeostasis with the interfacing microenvironment. Although IL-33 and its receptor ST2/ILRL1 are known to be increased and associated with IBD, studies using animal models of colitis to address the mechanism have yielded ambiguous results, suggesting both pathogenic and protective functions. Unlike those previously published studies, we focused on the functional role of IL-33/ST2 during an extended (2-wk) recovery period after initial challenge in dextran sodium sulfate (DSS)-induced colitic mice. Our results show that during acute, resolving colitis the normal function of endogenous IL-33 is protection, and the lack of either IL-33 or ST2 impedes the overall recovery process, while exogenous IL-33 administration during recovery dramatically accelerates epithelial restitution and repair, with concomitant improvement of colonic inflammation. Mechanistically, we show that IL-33 stimulates the expression of a network of microRNAs (miRs) in the Caco2 colonic intestinal epithelial cell (IEC) line, especially miR-320, which is increased by >16-fold in IECs isolated from IL-33-treated vs. vehicle-treated DSS colitic mice. Finally, IL-33-dependent in vitro proliferation and wound closure of Caco-2 IECs is significantly abrogated after specific inhibition of miR-320A. Together, our data indicate that during acute, resolving colitis, IL-33/ST2 plays a crucial role in gut mucosal healing by inducing epithelial-derived miR-320 that promotes epithelial repair/restitution and the resolution of inflammation.

Specific Loss Power of Co/Li/Zn-Mixed Ferrite Powders for Magnetic Hyperthermia.

An important research effort on the design of the magnetic particles is increasingly required to optimize the heat generation in biomedical applications, such as magnetic hyperthermia and heat-assisted drug release, considering the severe restrictions for the human body's exposure to an alternating magnetic field. Magnetic nanoparticles, considered in a broad sense as passive sensors, show the ability to detect an alternating magnetic field and to transduce it into a localized increase of temperature. In this context, the high biocompatibility, easy synthesis procedure and easily tunable magnetic properties of ferrite powders make them ideal candidates. In particular, the tailoring of their chemical composition and cation distribution allows the control of their magnetic properties, tuning them towards the strict demands of these heat-assisted biomedical applications. In this work, Co0.76Zn0.24Fe2O4, Li0.375Zn0.25Fe2.375O4 and ZnFe2O4 mixed-structure ferrite powders were synthesized in a 'dry gel' form by a sol-gel auto-combustion method. Their microstructural properties and cation distribution were obtained by X-ray diffraction characterization. Static and dynamic magnetic measurements were performed revealing the connection between the cation distribution and magnetic behavior. Particular attention was focused on the effect of Co2+ and Li+ ions on the magnetic properties at a magnetic field amplitude and the frequency values according to the practical demands of heat-assisted biomedical applications. In this context, the specific loss power (SLP) values were evaluated by ac-hysteresis losses and thermometric measurements at selected values of the dynamic magnetic fields.

Gradient-Based Automatic Lookup Table Generator for Radiative Transfer Models.

Physically based radiative transfer models (RTMs) are widely used in Earth observation to understand the radiation processes occurring on the Earth's surface and their interactions with water, vegetation, and atmosphere. Through continuous improvements, RTMs have increased in accuracy and representativity of complex scenes at expenses of an increase in complexity and computation time, making them impractical in various remote sensing applications. To overcome this limitation, the common practice is to precompute large lookup tables (LUTs) for their later interpolation. To further reduce the RTM computation burden and the error in LUT interpolation, we have developed a method to automatically select the minimum and optimal set of input-output points (nodes) to be included in an LUT. We present the gradient-based automatic LUT generator algorithm (GALGA), which relies on the notion of an acquisition function that incorporates: 1) the Jacobian evaluation of an RTM and 2) the information about the multivariate distribution of the current nodes. We illustrate the capabilities of GALGA in the automatic construction and optimization of MODTRAN-based LUTs of different dimensions of the input variables space. Our results indicate that when compared with a pseudorandom homogeneous distribution of the LUT nodes, GALGA reduces:1) the LUT size by >24%; 2) the computation time by 27%; and 3) the maximum interpolation relative errors by at least 10%. It is concluded that an automatic LUT design might benefit from the methodology proposed in GALGA to reduce interpolation errors and computation time in computationally expensive RTMs.

Geosystemics View of Earthquakes.

Earthquakes are the most energetic phenomena in the lithosphere: their study and comprehension are greatly worth doing because of the obvious importance for society. Geosystemics intends to study the Earth system as a whole, looking at the possible couplings among the different geo-layers, i.e., from the earth's interior to the above atmosphere. It uses specific universal tools to integrate different methods that can be applied to multi-parameter data, often taken on different platforms (e.g., ground, marine or satellite observations). Its main objective is to understand the particular phenomenon of interest from a holistic point of view. Central is the use of entropy, together with other physical quantities that will be introduced case by case. In this paper, we will deal with earthquakes, as final part of a long-term chain of processes involving, not only the interaction between different components of the Earth's interior but also the coupling of the solid earth with the above neutral or ionized atmosphere, and finally culminating with the main rupture along the fault of concern. Particular emphasis will be given to some Italian seismic sequences.

Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma.

BACKGROUND & AIMS: De novo synthesis of guanosine diphosphate (GDP)-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or tissue specific transplantation antigen P35B [TSTA3]). GMDS deletions and mutations are found in 6%-13% of colorectal cancers; these mostly affect the ascending and transverse colon. We investigated whether a lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. METHODS: FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx-/- mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by enzyme-linked immunosorbent assays to measure cytokine levels; T cells also were collected and analyzed. Fecal samples were analyzed by 16s ribosomal RNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx-/- or control mice (Ly5.2) into irradiated 8-week-old Fx-/- or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided). RESULTS: Fx-/- mice developed colitis and serrated-like lesions. The intestinal pathology of Fx-/- mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx-/- mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency altered the composition of the fecal microbiota, reduced mucosal barrier function, and altered epithelial proliferation marked by Ki67. Fx-/- mice receiving control bone marrow cells had intestinal inflammation and dysplasia, and reduced expression of cytokines produced by cytotoxic T cells. Human sessile serrated adenomas and right-sided colorectal tumors with epigenetic loss of MutL homolog 1 (MLH1) had lost or had lower levels of HES1 than other colorectal tumor types or nontumor tissues. CONCLUSIONS: In mice, fucosylation deficiency leads to colitis and adenocarcinoma, loss of Notch activation, and down-regulation of Hes1. HES1 loss correlates with the development of human right-sided colorectal tumors with epigenetic loss of MLH1. These findings indicate that carcinogenesis in a subset of colon cancer is consequent to a molecular mechanism driven by fucosylation deficiency and/or HES1-loss.

Hysteresis losses and specific absorption rate measurements in magnetic nanoparticles for hyperthermia applications.

BACKGROUND: Magnetic hysteresis loops areas and hyperthermia on magnetic nanoparticles have been studied with the aim of providing reliable and reproducible methods of measuring the specific absorption rate (SAR). METHODS: The SAR of Fe3O4 nanoparticles with two different mean sizes, and Ni1-xZnxFe2O4 ferrites with 0 ≤ x ≤ 0.8 has been measured with three approaches: static hysteresis loops areas, dynamic hysteresis loops areas and hyperthermia of a water solution. For dynamic loops and thermometric measurements, specific experimental setups have been developed, that operate at comparable frequencies (≈ 69kHz and ≈ 100kHz respectively) and rf magnetic field peak values (up to 100mT). The hyperthermia setup has been fully modelled to provide a direct measurement of the SAR of the magnetic nanoparticles by taking into account the heat exchange with the surrounding environment in non-adiabatic conditions and the parasitic heating of the water due to ionic currents. RESULTS: Dynamic hysteresis loops are shown to provide an accurate determination of the SAR except for superparamagnetic samples, where the boundary with a blocked regime could be crossed in dynamic conditions. Static hysteresis loops consistently underestimate the specific absorption rate but can be used to select the most promising samples. CONCLUSIONS: A means of reliably measure SAR of magnetic nanoparticles by different approaches for hyperthermia applications is presented and its validity discussed by comparing different methods. GENERAL SIGNIFICANCE: This work fits within the general subject of metrological traceability in medicine with a specific focus on magnetic hyperthermia. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

Quantification of the Void Volume in Single-Crystal Silicon.

This paper investigates the use of a method based on Cu decoration and neutron activation to determine the total volume of voids in a silicon single crystal. A measurement protocol was developed and tested in an experiment carried out with a 5 cm3 volume and 10 g mass high-purity natural silicon sample. The few percent uncertainty reached in the determination of the Cu concentration, at a 1014 cm-3 level, makes this method a candidate to set an upper limit to the concentration of the vacancies contributing to the void volume in the enriched silicon material used to determine the Avogadro constant.

Surgical management of early endometrial cancer: an update and proposal of a therapeutic algorithm.

In the last few years technical improvements have produced a dramatic shift from traditional open surgery towards a minimally invasive approach for the management of early endometrial cancer. Advancement in minimally invasive surgical approaches has allowed extensive staging procedures to be performed with significantly reduced patient morbidity. Debate is ongoing regarding the choice of a minimally invasive approach that has the most effective benefit for the patients, the surgeon, and the healthcare system as a whole. Surgical treatment of women with presumed early endometrial cancer should take into account the features of endometrial disease and the general surgical risk of the patient. Women with endometrial cancer are often aged, obese, and with cardiovascular and metabolic comorbidities that increase the risk of peri-operative complications, so it is important to tailor the extent and the radicalness of surgery in order to decrease morbidity and mortality potentially derivable from unnecessary procedures. In this regard women with negative nodes derive no benefit from unnecessary lymphadenectomy, but may develop short- and long-term morbidity related to this procedure. Preoperative and intraoperative techniques could be critical tools for tailoring the extent and the radicalness of surgery in the management of women with presumed early endometrial cancer. In this review we will discuss updates in surgical management of early endometrial cancer and also the role of preoperative and intraoperative evaluation of lymph node status in influencing surgical options, with the aim of proposing a management algorithm based on the literature and our experience.

Italian version of University of California at Los Angeles (UCLA) Activity Score: cross-cultural adaptation.

Over the last 10 years, patient-oriented evaluations using questionnaires have become an important aspect of clinical outcome studies. Any questionnaire must be translated and culturally adapted in order to be used with different language groups, and the translated version must then be evaluated for reliability, validity and responsiveness which are fundamental attributes of any measurement tool. The aim of this study is the validation, translation and cross-cultural adaptation of the Italian version of UCLA activity Score, following the Guillemin criteria. The results show that our Italian version of the UCLA score has the following: reproducibility expressed as ICC=0.994, an internal consistency calculated as Spearman-Brown coefficient=0.754 and finally the construct validity has demonstrated a significant Pearson's correlation coefficient with other validated hip questionnaires.

Candida tropicalis Affects Candida albicans Virulence by Limiting Its Capacity to Adhere to the Host Intestinal Surface, Leading to Decreased Susceptibility to Colitis in Mice.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity of the fungus to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of a C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. The colitis severity was evaluated using histology and a colonoscopy. The mice were mono-inoculated with C. albicans or C. tropicalis or co-challenged with both species. The mice were administered 3% DSS to induce acute colitis. The biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) and dry-weight assays. The abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. The co-challenged mice showed a decreased colitis severity compared to the mono-inoculated mice. The dry-weight assay demonstrated a marked decrease in C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface, leading to a reduction in biofilm formation.

Undifferentiated pleomorphic sarcoma with osteoclast-like giant cells of the female breast.

The authors describe a case of undifferentiated pleomorphic sarcoma of the breast occurring in a 50-year-old woman who presented with a palpable mass in her right breast. She first noticed the mass one month previously. Core needle biopsy showed connective tissue including epithelioid and spindle cells. The patient underwent total mastectomy without axillary lymph node dissection. Based on examination of the excised tumor, the initial pathologic diagnosis was atypical spindle-shaped and ovoid cells with uncertain malignant potential. Histological findings with immunomarkers led to the final diagnosis of undifferentiated pleomorphic sarcoma.This case highlights a rare and interesting variant of primary breast sarcoma and the important role of immunohistochemistry in defining histological type and differential diagnosis. Hence, undifferentiated pleomorphic sarcoma has been a diagnosis of exclusion performed through sampling and critical use of ancillary diagnostic techniques.

An unusual case of orbito-frontal rod fence stab injury with a good outcome.

BACKGROUND: High-energy non-missile penetrating injuries (stab injuries) account for a small percentage of penetrating head injuries and they present a series of special features. CASE PRESENTATION: A 35-year-old man suffered orbito-frontal? and trans-cranial injuries after falling five meters from a terrace onto a rod iron fence. The removal of the metal rod was performed outside the operating room. The orbital roof was exposed and repaired through a bifrontal craniotomy and the frontal sinuses were cranialised. The orbital floor and zygoma were plated with micro-screws. CONCLUSION: The patient recovered without significant complications, apart from a slight paresis of the right superior rectus; the ocular globe remained intact.The positive outcome obtained in this very challenging case is attributable to the competency of the Neurotrauma Unit and to the use of a synergistic approach which involved the contribution of neurosurgeons, maxillo-facial surgeons, radiologists and anaesthesiologists.

Mycobiome and Inflammatory Bowel Disease: Role in Disease Pathogenesis, Current Approaches and Novel Nutritional-based Therapies.

Inflammatory bowel disease (IBD), a disorder characterized by chronic inflammation of the gastrointestinal (GI) tract and a range of adverse health effects including diarrhea, abdominal pain, vomiting, and bloody stools, affects nearly 3.1 million genetically susceptible adults in the United States today. Although the etiology of IBD remains unclear, genetics, stress, diet, and gut microbiota dysbiosis- especially in immunocompromised individuals- have been identified as possible causes of disease. Although previous research has largely focused on the role of bacteria in IBD pathogenesis, recently observed alterations of fungal load and biodiversity in the GI tract of afflicted individuals suggest interkingdom interactions amongst different gut microbial communities, particularly between bacteria and fungi. These discoveries point to the potential utilization of treatment approaches such as antibiotics, antifungals, probiotics, and postbiotics that target both bacteria and fungi in managing IBD. In this review, we discuss the impact of specific fungi on disease pathogenesis, with a focus on the highly virulent genus Candida and how the presence of certain co-enzymes impacts its virulence. In addition, we evaluate current gut microbiome-based therapeutic approaches with the intention of better understanding the mechanisms behind novel therapies.

Recently observed alterations of fungal load in the gastrointestinal tract of IBD patients suggest interkingdom interactions amongst different gut microbial communities. These discoveries point to the potential utilization of antifungals and probiotics that target bacteria and fungi in managing IBD.

A Novel Probiotic Combination Ameliorates Crohn's Disease-Like Ileitis by Increasing Short-Chain Fatty Acid Production and Modulating Essential Adaptive Immune Pathways.

BACKGROUND: Crohn's disease (CD) represents a significant public health challenge. We identified a combination of beneficial probiotic strains (Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium breve) and amylase that may antagonize elevated bacterial pathogens in the inflamed gut. Our aim was to characterize the effect(s) of this novel probiotic supplement in SAMP1/YitFc (SAMP) mice with CD-like ileitis. METHODS: Three groups of 7-week-old SAMP mice were used in this study. The first experimental group was administered 1 dose of the probiotic supplement (probiotic strains + amylase) diluted in sterile phosphate-buffered saline (PBS) (0.25 mg in 100 µL of PBS) every day for 56 days through the gavage technique, the second group had a probiotic supplement (probiotic strains without amylase), and the third group was a control group in which animals were administered sterile PBS. At the end of the treatment, mice were sacrificed and ilea were collected for histological scoring of ileitis and NanoString analysis. Stool samples were evaluated by 16S ribosomal RNA and gas chromatography-mass spectrometry analyses. RESULTS: Histology scores showed that mice treated with probiotics + amylase had a significant decrease of ileitis severity compared with the other 2 groups. 16S ribosomal RNA and gas chromatography-mass spectrometry analysis showed that abundance of species belonging to genus Lachnoclostridium and Mucispirillum schaedleri were significantly increased compared with the other 2 groups, and this increase was associated with augmented production of short-chain fatty acids. NanoString data showed that 21 genes involved in B memory cell development and T cell infiltration were significantly upregulated in probiotic-treated mice and that 3 genes were significantly downregulated. CONCLUSIONS: Our data provide experimental proof for a beneficial effect of the designed probiotic formulation on the severity of CD-like ileitis in the SAMP mouse model, involving both alteration of intestinal genetic pathways and microbial rearrangements. Thus, we propose that this novel probiotic mixture should be further tested as an adjuvant therapy in the treatment of biofilm-associated disorders such as CD, in which it has been proven that polymicrobial imbalance plays a critical role in dysbiosis and gut inflammation.

In this study, we report that consumption of a novel probiotic and amylase mixture reduced intestinal inflammation in SAMP1/YitFc mice. These findings provide the rationale for clinical testing of the designed probiotic as an adjuvant therapy for Crohn's disease treatment.

Hydrocephalus As Possible Prodromal Manifestation of COVID-19: A Report of Two Cases.

Although the etiopathology of normal pressure hydrocephalus (NPH) is still not completely defined, several studies in recent years have highlighted the role of neuro-inflammation mediators in its development. During COVID-19, the infected host develops a multifaceted inflammatory syndrome, that may lead to an uncontrolled immune system response also localized in the host nervous system. In fact, the target of the viral Spike protein, the angiotensin-converting enzyme 2 (ACE2) receptors, is widely expressed in different areas of CNS such as the olfactory epithelium, and the choroid plexus. As for idiopathic NPH, the massive release of inflammatory mediators may result in altered CSF dynamics and consequent sudden clinical decompensation. We report the cases of two patients with a known iNPH condition, in which neurological symptoms suddenly worsened, requiring hospitalization, without any evident precipitating cause. Both patients tested positive for the COVID-19 virus shortly after the neurological impairment, which had occurred, therefore, during the incubation period of the infection. On the basis of our experience we advise, in cases of NPH patients with sudden neurological worsening, to perform a molecular COVID-19 swab at the moment of clinical impairment. We, therefore, recommend considering SARS-CoV-2 infection in the differential diagnosis of a sudden and otherwise unexplainable impairment of hydrocephalic patients. Furthermore, we believe clinicians should invite NPH patients to adopt adequate preventive measures to protect them from SARS-CoV-2 infection.

Effectiveness of mRNA COVID-19 Vaccines in Adolescents Over 6 Months.

BACKGROUND AND OBJECTIVES: On June 4, 2021, Italy launched the coronavirus disease 2019 (COVID-19) vaccination of adolescents to slow down the COVID-19 spread. Although clinical trials have evaluated messenger ribonucleic acid (mRNA) vaccine effectiveness in adolescents, there is limited literature on its real-world effectiveness. Accordingly, this study aimed to estimate the effectiveness of mRNA COVID-19 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild or severe COVID-19 in a cohort of Sicilian adolescents within a 6 month observation period. METHODS: A retrospective cohort study was conducted with adolescents aged 12 to 18 years, residents of Sicily, who were followed from July 15 to December 31, 2021. SARS-CoV-2 infections, mild and severe COVID-19, and COVID-19-related intubation or deaths during the study period were compared between subjects vaccinated with 2 doses of mRNA vaccines and unvaccinated individuals. The Cox regression analysis, adjusted for age and sex, was performed to compare the 2 groups. RESULTS: Overall, the study included a total at-risk population of 274 782 adolescents with 61.4% of them having completed the vaccination cycle by the end of the study. Unvaccinated subjects had higher incidence rates of SARS-CoV-2 (1043 × 10 000 vs 158.7 × 10 000 subjects), mild COVID-19 (27.7 × 10 000 vs 1.8 × 10 000 subjects) and severe COVID-19 (1.41 × 10 000 vs 0 subjects) compared with the vaccinated population. The estimated adjusted vaccine effectiveness against SARS-CoV-2 infection was 71.2%, reaching 92.1% and 97.9% against mild and severe COVID-19, respectively. CONCLUSIONS: This study provides rigorous evidence of mRNA COVID-19 vaccines' effectiveness in protecting adolescents from both SARS-CoV-2 infection and COVID-19.