a b s t r a c tThe intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m 2 . The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings.This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine.

Purpose The COVID-19 pandemic is importantly affecting the orthopaedic practice all over the world with Northern Italy being the first European area that faced the worst scenario. In this study, the changes in clinical practice occurred in an orthopaedic center in Milan are described. Methods Number and type of admissions, outpatients cancelled and preserved, emergency room, and intensive care unit activities have been analyzed in the timeframe of seven weeks since the beginning of the pandemic (from February 24th to April 10th) and compared with the same period in 2019. Results The planned surgical admissions declined from 2172 in 2019 to 664 in 2020 (69.42%, p < 0.0001), while emergencies increased from 158 to 268 (69.62%). The rehabilitation admissions declined from 414 to 69 (83.33%). The overall admission decreased by 63.52%, the trend showed a drop in the last weeks. Surgery performed in the COVID-19 operating room increased by 16.7% in the last week. Seven deaths occurred (0.7% of all orthopaedics and trauma admissions) compared with four (0.1%) which happened in the same period in 2019 (p = 0.004). Six of these patients were suffering from COVID-19. A total of 23,580 outpatients (93.8%) were cancelled. Emergency room consultations declined by 68.14% and 63.47% among white and green priority, respectively, while increased by 25% and 100% among yellow and red, respectively. Conclusion These numbers show the radical changed scenario in an orthopaedic center in Milan during COVID-19 pandemic. Elective surgery declined rapidly going close to zero, outpatient admissions were restricted to cases that cannot be postponed, while emergencies increased due to the role played by the hospital as referral orthopaedic centre during the pandemic. The still ongoing emergency will have important impacts on the overall orthopaedic healthcare management for the next months.

The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The full-blown COVID-19 can lead, in susceptible individuals, to premature death because of the massive viral proliferation, hypoxia, misdirected host immunoresponse, microthrombosis, and drug toxicities. Alike other coronaviruses, SARS-CoV-2 has a neuroinvasive potential, which may be associated with early neurological symptoms. In the past, the nervous tissue of patients infected with other coronaviruses was shown to be heavily infiltrated. Patients with SARS-CoV-2 commonly report dysosmia, which has been related to the viral access in the olfactory bulb. However, this early symptom may reflect the nasal proliferation that should not be confused with the viral access in the central nervous system of the host, which can instead be allowed by means of other routes for spreading in most of the neuroanatomical districts. Axonal, trans-synaptic, perineural, blood, lymphatic, or Trojan routes can gain the virus multiples accesses from peripheral neuronal networks, thus ultimately invading the brain and brainstem. The death upon respiratory failure may be also associated with the local inflammation-and thrombi-derived damages to the respiratory reflexes in both the lung neuronal network and brainstem center. Beyond the infection-associated neurological symptoms, long-term neuropsychiatric consequences that could occur months after the host recovery are not to be excluded. While our article does not attempt to fully comprehend all accesses for host neuroinvasion, we aim at stimulating researchers and clinicians to fully consider the neuroinvasive potential of SARS-CoV-2, which is likely to affect the peripheral nervous system targets first, such as the enteric and pulmonary nervous networks. This acknowledgment may shed some Briguglio et al.Host Dysosmia and SARS-CoV-2 Neuroinvasion light on the disease understanding further guiding public health preventive efforts and medical therapies to fight the pandemic that directly or indirectly affects healthy isolated individuals, quarantined subjects, sick hospitalized, and healthcare workers.

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SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.

These results demonstrate that a regular, long-term intake of various synbiotics may improve health by reducing the incidence and severity of respiratory diseases during the cold season.

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