Apathy as Marker of Frail Status

Frailty is a complex and dynamic condition associated with aging. This condition is characterised by the difficult adaptation of an old subject to new challenges occurring during life. Frailty is supposed to be due to the progressive decrease of physiological reserves and multiorgan and multisystem change. It coincides with a reduced or absent resilience. In general comorbidities like hypertension, heart disease, inflammation and infectious diseases are potential risk factors for and psychophysical decline. The aim of this work is to highlight the importance of impaired cognition as factor predisposing to frailty. The authors are convinced and suggest that the presence of neurobehavioral disturbance like apathy associated to impaired executive function could be the major predisposing factor for frailty and unsuccessful aging. Unfortunately available literature largely underestimates the presence of these factors. Thus to better identify markers of frailty, a good neuropsychological assessment and the evaluation of behavioural disturbances are suggested

Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients

Effect of SARS-CoV-2 infection in pregnancy on CD147, ACE2 and HLA-G expression

Introduction: Recent studies reported a differential expression of both ACE2 and CD147 in pregnant women associated to SARS-CoV-2 placental infection. The aim of this study is to further investigate the placental SARS-CoV-2 infection and the potential effect on protein expression (ACE2, CD147, HLA-G and CD56). Methods: The study was on three subgroups: i) 18 subjects positive for SARS-CoV-2 swab at delivery; ii) 9 subjects that had a positive SARS-CoV-2 swab during pregnancy but resulted negative at delivery; iii) 11 control subjects with physiological pregnancy and with no previous or concomitant SARS-CoV-2 swab positivity. None of the subjects were vaccinated for SARS-CoV-2 infection. The placenta samples were analyzed for SARS-CoV-2 NP (Nucleocapsid protein) positivity and the expression of ACE2, CD147, HLA-G and CD56. Results: We observed a higher percentage of SARS-CoV-2 NP positive placenta samples in the group of SARS-CoV-2 PCR positive at delivery in comparison with SARS-CoV-2 PCR negative at delivery. The localization of SARS-CoV-2 NP positivity in placenta samples was mainly in syncytiotrophoblast (ST) of SARS-CoV-2 PCR positive at delivery group and in extra-villous trophoblast (EVT) of SARS-CoV-2 PCR negative at delivery group. CD147, HLA-G positivity was higher in ST of SARS-CoV-2 PCR positive at delivery group, while CD56-expressing immune cells were decreased in comparison with control subjects. Discussion: We confirmed the ability of SARS-CoV-2 to infect placenta tissues. The simultaneous SARS-CoV-2 swab positivity at delivery and the positivity of the placenta tissue for SARS-CoV-2 NP seems to create an environment that modifies the expression of specific molecules, as CD147 and HLA-G. These data suggest a possible impact of SARS-CoV-2 infection during pregnancy, that might be worthy to be monitored also in vaccinated subjects

Apathy as Marker of Frail Status

Frailty is a complex and dynamic condition associated with aging. This condition is characterised by the difficult adaptation of an old subject to new challenges occurring during life. Frailty is supposed to be due to the progressive decrease of physiological reserves and multiorgan and multisystem change. It coincides with a reduced or absent resilience. In general comorbidities like hypertension, heart disease, inflammation and infectious diseases are potential risk factors for and psychophysical decline. The aim of this work is to highlight the importance of impaired cognition as factor predisposing to frailty. The authors are convinced and suggest that the presence of neurobehavioral disturbance like apathy associated to impaired executive function could be the major predisposing factor for frailty and unsuccessful aging. Unfortunately available literature largely underestimates the presence of these factors. Thus to better identify markers of frailty, a good neuropsychological assessment and the evaluation of behavioural disturbances are suggested

Gait impairment in neurological disorders: a new technological approach

Gait recovery is considered one of the main objectives of rehabilitation interventions in neurological disabilities, as restricted movement can significantly reduce an individual’s ability to take part in normal activities of daily living. Locomotor training has been shown to improve gait rehabilitation. Studies have recently been published on the use of robots and other devices in patients with gait disabilities, particularly in the rehabilitation of the lower limbs. However, analysis of the recent literature reveals a relative paucity of strong methodological studies. The evidence that is available, while strong, is not yet sufficient to allow definite conclusions to be drawn regarding the efficacy of these devices. From these considerations, it is clear that validated and standardized methods need to be adopted for each of the different systems available. This would help to clarify the indications for and correct use of robotic devices in the different neurological disorder

Homotaurine induces measurable changes of short latency afferent inhibition in a group of mild cognitive impairment individuals

Current treatment options for patients with Alzheimer's disease (AD) are limited at providing symptomatic relief, with no effects on the underlying pathophysiology. Recently, advances in the understanding of the AD pathogenesis highlighted the role of ABeta (Aβ) oligomers particularly interfering with mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD). These findings led to the development of potential anti-amyloid therapies, and among them homotaurine, a glycosaminoglycan mimetic designed to interfere with the actions of Aβ early in the cascade of amyloidogenic events, and by its γ-aminobutyric acid type (GABA) A receptor affinity. Recently, we showed that AD patients have impaired LTP-like cortical plasticity, as measured by standard theta burst stimulation protocols applied over the primary motor cortex (M1). Furthermore, AD patients have a weakened short latency afferent inhibition (SLAI), a neurophysiological measure of central cholinergic transmission, which changes reflect the cholinergic dysfunction occurring in the pathology. Here, we aimed at investigating whether homotaurine administration could modulate in vivo measured mechanisms of synaptic plasticity, namely LTP and LTD, and also SLAI in a group of mild cognitive impaired patients. We observed that homotaurine administration did not induce relevant changes of both LTP and LTD recordings, while induced changes of SLAI in our group of patients. We suggest that homotaurine effects are dependent on changes of cortical GABA transmission suggesting a potential role for this compound in ameliorating the cholinergic transmission by modulating the inhibitory cortical activity

SARS-CoV-2 nucleocapsid-protein and ultrastructural modifications in small bowel of a four week negative COVID-19 patient

Dear Editor, HumanCoVs (HCoVs) account for up to 30% of infections of the upper respiratory tract and 8.1% of enteritis.1,2 However, related to the wide distribution of ACE2 in human tissues, several reports already hypothesized that SARS-CoV-2 may directly infect multiple organs, including liver, stomach, ileum and colon.3 Our patient, a man in his fifties with no prior medical history, had a positive to nop-swab for SARS-CoV-2 RNA four days after the start of symptoms. He was treated at home with hydroxychloroquine and azithromycin for seven days. The patient recovered and had a repeated two nop-swab, both with negative results. After two weeks he was admitted to the Emergency Department complaining of stomach pain followed by a syncopal episode and intestinal bleeding. Asymptomatic bilateral interstitial pneumonia was documented by CT scan. A colonscopy detected an ileocecal valve proximal ulceration (supplementary Fig 1), without active bleeding. The patient underwent emergency surgery due to an hypotensive episode associated with haematic stools. Terminal ileum and cecum were resected as well as Meckel diverticulum. At the histological examination, terminal ileum wall showed chronic inflammatory infiltrates with prevalence of lymphocytes, focal ulceration of both mucosa (Fig. 1d) and submucosa (Fig. 1e). Abnormally enlarged and tortuous thick-walled veins were seen in the submucosa. IHC analysis with anti-SARS-CoV-2 nucleocapsid-protein revealed the presence of viral protein expression in epithelial cell of ulcerated intestinal mucosa (cytoplasmic staining) and in a minority of lymphocytes (Fig. 1d); no staining in the submucosa (Fig. 1e). We also analyzed the expression of a non-classical MHC-I molecule, Human Leukocyte Antigen-G (HLA-G), that blocks endothelial cell proliferation and vessel formation.4 We observed HLA-G in epithelial cells of the intestinal mucosa and in some lymphocytes (Fig. 1d), in correspondence of SARS-CoV-2 positive sites. In the submucosa, HLA-G expression was detectable only in few lymphocytes (Fig. 1e). Transmission Electron Microscopy (TEM) analysis revealed a significantly different morphological microvilli profile,the intestinal tract of a normal ileum from a subject pre-COVID-19 appearance, showed well organized and aligned microvilli, with a regular distribution protruding from the apical cell membrane (acm) and an homogeneous glycocalyx (gc) (Fig. 1f and g). The tissue, examined in the area without focal ulceration showed a morphology similar to the control (Fig. 1h and i). Regarding the ulceration area, microvilli appeared shorter than those in the not ulcerated area, partially depeneed beyond the acm, and gc appeared disorganized and almost absent showing a relevant cytopatic effect (Fig. 1j and k)

Relevance of VEGF and CD147 in different SARS-CoV-2 positive digestive tracts characterized by thrombotic damage

Several evidence suggests that, in addition to the respiratory tract, also the gastrointestinal tract is a main site of severe acute respiratory syndrome CoronaVirus 2 (SARS-CoV-2) infection, as an example of a multi-organ vascular damage, likely associated with poor prognosis. To assess mechanisms SARS-CoV-2 responsible of tissue infection and vascular injury, correlating with thrombotic damage, specimens of the digestive tract positive for SARS-CoV-2 nucleocapsid protein were analyzed deriving from three patients, negative to naso-oro-pharyngeal swab for SARS-CoV-2. These COVID-19-negative patients came to clinical observation due to urgent abdominal surgery that removed different sections of the digestive tract after thrombotic events. Immunohistochemical for the expression of SARS-CoV-2 combined with a panel of SARS-CoV-2 related proteins angiotensin-converting enzyme 2 receptor, cluster of differentiation 147 (CD147), human leukocyte antigen-G (HLA-G), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was performed. Tissue samples were also evaluated by electron microscopy for ultrastructural virus localization and cell characterization. The damage of the tissue was assessed by ultrastructural analysis. It has been observed that CD147 expression levels correlate with SARS-CoV-2 infection extent, vascular damage and an increased expression of VEGF and thrombosis. The confirmation of CD147 co-localization with SARS-CoV-2 Spike protein binding on gastrointestinal tissues and the reduction of the infection level in intestinal epithelial cells after CD147 neutralization, suggest CD147 as a possible key factor for viral susceptibility of gastrointestinal tissue. The presence of SARS-CoV-2 infection of gastrointestinal tissue might be consequently implicated in abdominal thrombosis, where VEGF might mediate the vascular damage