Heparanase and macrophage interplay in the onset of liver fibrosis

Abstract The heparan sulfate endoglycosidase heparanase (HPSE) is involved in tumor growth, chronic inflammation and fibrosis. Since a role for HPSE in chronic liver disease has not been demonstrated to date, the current study was aimed at investigating the involvement of HPSE in the pathogenesis of chronic liver injury. Herein, we revealed that HPSE expression increased in mouse livers after carbon tetrachloride (CCl4)-mediated chronic induction of fibrosis, but with a trend to decline during progression of the disease. In mouse fibrotic liver tissues HPSE immunostaining was restricted in necro-inflammatory areas, co-localizing with F4/80 macrophage marker and TNF-α. TNF-α treatment induced HPSE expression as well as HPSE secretion in U937 macrophages. Moreover, macrophage-secreted HPSE regulated the expression of α-SMA and fibronectin in hepatic stellate LX-2 cells. Finally, HPSE activity increased in the plasma of patients with liver fibrosis but it inversely correlated with liver stiffness. Our results suggest the involvement of HPSE in early phases of reaction to liver damage and inflammatory macrophages as an important source of HPSE. HPSE seems to play a key role in the macrophage-mediated activation of hepatic stellate cells (HSCs), thus suggesting that HPSE targeting could be a new therapeutic option in the treatment of liver fibrosis

Otolaryngologic symptoms in multiple sclerosis: a review

Many symptoms of multiple sclerosis may affect the ear, nose and throat. The most common otolaryngologic symptoms of multiple sclerosis are speech disorders, followed by sleep disorders, vertigo and disequilibrium, dysphagia, smell alterations, and hearing loss. Less common symptoms include sialorrhea, facial palsy, taste alterations, trigeminal neuralgia and tinnitus. The origin of otolaryngologic symptoms in multiple sclerosis is mainly central, although increasing evidence also suggests a peripheral involvement. Otolaryngologic symptoms in multiple sclerosis may have different clinical presentations; they can appear in different stages of the pathology, in some cases they can be the presenting symptoms and their worsening may be correlated with reactivation of the disease. Many of these symptoms significantly affect the quality of life or patients and lead to increased morbidity and mortality. Otolaryngologic symptoms are common in multiple sclerosis; however, they are often overlooked. In many cases, they follow the relapsing-remitting phases of the disease, and may spontaneously disappear, leading to a delay in multiple sclerosis diagnosis. Clinicians should be aware of otolaryngologic symptoms of multiple sclerosis, especially when they are associated to neurologic symptoms, as they may be early signs of a still undiagnosed multiple sclerosis or could help monitor disease progression in already diagnosed patients

Quasi-static and low-velocity impact behavior of intraply hybrid flax/basalt composites

In an attempt to increase the low-velocity impact response of natural fiber composites, a new hybrid intraply woven fabric based on flax and basalt fibers has been used to manufacture laminates with both thermoplastic and thermoset matrices. The matrix type (epoxy or polypropylene (PP) with or without a maleated coupling agent) significantly affected the absorbed energy and the damage mechanisms. The absorbed energy at perforation for PP-based composites was 90% and 50% higher than that of epoxy and compatibilized PP composites, respectively. The hybrid fiber architecture counteracted the influence of low transverse strength of flax fibers on impact response, irrespective of the matrix type. In thermoplastic laminates, the matrix plasticization delayed the onset of major damage during impact and allowed a better balance of quasi-static properties, energy absorption, peak force, and perforation energy compared to epoxy-based composites

Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA, revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep

Blood and skin-derived Sezary cells: differences in proliferation-index, activation of PI3K/AKT/mTORC1 pathway and its prognostic relevance

Sézary syndrome (SS) is a rare and aggressive variant of Cutaneous T-Cell Lymphoma characterized by neoplastic distribution mainly involving blood, skin, and lymph-node. Although a role of the skin microenvironment in SS pathogenesis has long been hypothesized, its function in vivo is poorly characterized. To deepen this aspect, here we compared skin to blood-derived SS cells concurrently obtained from SS patients highlighting a greater proliferation-index and a PI3K/AKT/mTORC1 pathway activation level, particularly of mTOR protein, in skin-derived-SS cells. We proved that SDF-1 and CCL21 chemokines, both overexpressed in SS tissues, induce mTORC1 signaling activation, cell proliferation and Ki67 up-regulation in a SS-derived cell line and primary-SS cells. In a cohort of 43 SS cases, we observed recurrent copy number variations (CNV) of members belonging to this cascade, namely: loss of LKB1 (48%), PTEN (39%) and PDCD4 (35%) and gains of P70S6K (30%). These alterations represent druggable targets unraveling new therapeutic treatments as metformin here evaluated in vitro. Moreover, CNV of PTEN, PDCD4, and P70S6K, evaluated individually or in combination, are associated with reduced survival of SS patients. These data shed light on effects in vivo of skin-SS cells interaction underlying the prognostic and therapeutic relevance of mTORC1 pathway in SS

Universal newborn hearing screening in the Lazio region, Italy

Background: The introduction of Universal Newborn Hearing Screening (UNHS) programs has drastically contributed to the early diagnosis of hearing loss in children, allowing prompt intervention with significant results on speech and language development in affected children. UNHS in the Lazio region has been initially deliberated in 2012; however, the program has been performed on a universal basis only from 2015. The aim of this retrospective study is to present and discuss the preliminary results of the UNHS program in the Lazio region for the year 2016, highlighting the strengths and weaknesses of the program. Methods: Data from screening facilities in the Lazio region for year 2016 were retrospectively analyzed. Data for Level I centers were supplied by the Lazio regional offices; data for Level II and III centers were provided by units that participated to the study. Results: During 2016, a total of 44,805 babies were born in the Lazio region. First stage screening was performed on 41,821 children in 37 different birth centers, with a coverage rate of 93.3%. Of these, 38.977 (93.2%) obtained a "pass" response; children with a "refer" result in at least one ear were 2844 (6.8%). Data from Level II facilities are incomplete due to missing reporting, one of the key issues in Lazio UNHS. Third stage evaluation was performed on 365 children in the three level III centers of the region, allowing identification of 70 children with unilateral (40%) or bilateral (60%) hearing loss, with a prevalence of 1.6/1000. Conclusions: The analysis of 2016 UNHS in the Lazio region allowed identification of several strengths and weaknesses of the initial phase of the program. The strengths include a correct spread and monitoring of UNHS among Level I facilities, with an adequate coverage rate, and the proper execution of audiological monitoring and diagnosis among Level III facilities. Weakness, instead, mainly consisted in lack of an efficient and automated central process for collecting, monitoring and reporting of data and information

Enhanced Anti-Fouling Behavior and Performance of PES Membrane by UV Treatment

An easy method to prepare hydrophilic PES membranes with anti-fouling properties was developed by UV-polymerization of poly vinyl pirrolidone (PVP) on membrane surfaces. The modified membrane surfaces were analyzed by ATR-FTIR, and the new hydrophilic nature of the membranes was determined by contact angle measurements. The novel membranes were prepared using Rhodiasolv® Polarclean as a green solvent and compared with a control PES membrane, without the exposure at the hydrophilization procedure. The influences of the UV lamp distance (15 and 30 cm) and the exposure time (0 cm to 60 cm) were evaluated. All membranes were characterized in terms of surface morphology, porosity, pore size, and pure water permeability (PWP). The treated membranes resulted in an increase in hydrophilicity and in improved performances in terms of PWP and foulant rejection. In particular, an anti-fouling test was performed using a solution of 100 mg/L of humic acid (HA) as a model foulant. The UV-treated membrane efficiency, compared with a commercial PES membrane, showed a recovery of about 97%, confirming that these membranes can be applied in wastewater treatment

Severe bloodstream infection due to KPC-producer e coli in a renal transplant recipient treated with the double-carbapenem regimen and analysis of in vitro synergy testing a case report

Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited thera- peutic options, innovative antimicrobial combinations against carbape- nem-resistant Enterobacteriaceae causing severe infections are necessary. A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was compli- cated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Kle- bisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of merope- nem plus ertapenem) and a potent synergistic and bactericidal activity of this un-conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock. The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients

Sense of Coherence (SOC) of Italian healthcare workers during the Covid-19 pandemic: analysis of associated factors

Introduction: The COVID-19 pandemic has posed significant challenges for healthcare workers worldwide, potentially affecting their sense of coherence (SOC) and overall well-being. This study aimed to identify factors associated with different levels of SOC among healthcare workers. Methods: A cross-sectional study was conducted among 628 healthcare workers. SOC scores were assessed using a standardized questionnaire, and data on demographic characteristics, length of service, geographic location, and pandemic-related experiences were collected. Statistical analyses were performed to identify associations between these factors and SOC. Results: Healthcare workers had a lower average SOC score (mean: 57.1) compared to the national average in Italy (mean: 60.3). Younger age and shorter length of service were associated with a higher risk of low SOC (p<0.0001). Healthcare workers in the northwestern regions of Italy had an increased risk of low SOC compared to their counterparts in the northeastern regions (p=0.0336). Adverse pandemic-related experiences and worsening social relationships were also associated with a higher risk of low SOC (p<0.0001). Conclusions: This study highlights the unique challenges and stressors faced by healthcare workers during the COVID-19 pandemic and their impact on SOC. Age, length of service, geographic location, and social were significant factors influencing SOC levels. Targeted interventions are needed to enhance SOC and well-being, particularly for younger and newly employed healthcare workers. Strategies promoting social connections, work-life balance, and psychological support services are crucial to support healthcare workers' resilience and coping abilities

Tamarix arborea var. arborea and Tamarix parviflora: Two species valued for their adaptability to stress conditions

The choice of stress resistant and highly adaptable species is a fundamental step for landscaping and ornamental purposes in arid and coastal environments such as those in the Mediterranean basin. The genus Tamarix L. includes about 90 species with a high endurance of adversity. We investigated the water relations and photosynthetic response of Tamarix arborea (Sieb. ex Ehrenb.) Bge. var. arborea and T. parviflora DC. growing in an urban environment. Both species showed no evidence of drought or salt stress in summer, and appeared to follow two strategies with T. arborea var. arborea investing in high carbon gain at the beginning of the summer, and then reducing photosynthetic activity at the end of the season, and T. parviflora showing lower but constant levels of photosynthetic activity throughout the vegetative season. For landscaping and ornamental purposes, we suggest T. arborea var. arborea when a fast-growing, high-cover species is necessary, and T. parviflora when less-invasive species are required