The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.

AIMS: Paediatric low-grade gliomas (pLGGs) are a heterogeneous group of brain tumours associated with a high overall survival: however, they are prone to recur and supratentorial lesions are difficult to resect, being associated with high percentage of disease recurrence. Our aim was to shed light on the biology of pLGGs. METHODS: We performed microRNA profiling on 45 fresh-frozen grade I tumour samples of various histological classes, resected from patients aged ≤16 years. We identified 93 microRNAs specifically dysregulated in tumours as compared to non-neoplastic brain tissue. Pathway analysis of the microRNAs signature revealed PI3K/AKT signalling as one of the centrally enriched oncogenic signalling. To date, activation of the PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been fully investigated yet. RESULTS: One of the most markedly down-regulated microRNAs in our supratentorial pLGGs cohort was miR-139-5p, whose targets include the gene encoding the PI3K's (phosphatidylinositol 3-kinase) catalytic unit, PIK3CA. We investigated the role of miR-139-5p in regulating PI3K/AKT signalling by the use of human cell cultures derived from supratentorial pLGGs. MiR-139-5p overexpression inhibited pLGG cell proliferation and decreased the phosphorylation of PI3K target AKT and phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of PI3K/AKT/mTORC1 signalling activation. The effect of miR-139-5p was mediated by PI3K inhibition, as suggested by the decrease in proliferation and phosphorylation of AKT and p70 S6K after treatment with the direct PI3K inhibitor LY294002. CONCLUSIONS: These findings provide the first evidence that down-regulation of miR-139-5p in supratentorial pLGG drives cell proliferation by derepressing PI3K/AKT signalling.

SARS-CoV-2 systemic infection in a kidney transplant recipient: sequence analysis in clinical specimens.

OBJECTIVE: Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection. PATIENTS AND METHODS: Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood. RESULTS: Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool. CONCLUSIONS: The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity.

[Exposure to crystalline silica in the air during renovation of residential buildings]. / Esposizione a silice libera cristallina nelle attività di ristrutturazione in edilizia abitativa.

Exposure to respirable cristalline silica dust during construction activities can cause silicosis and, in accordance with International Agency for Research on Cancer (IARC), even lung cancer. Among the different facets of construction, residential buildings are of particular interest because the lack of exposure data for workers employed. In this sector a dry sand-blasting of brick ceiling and renewal activities has been investigated. The survey has been carried out in a civil dwelling and 58 samples have been collected using the SKC aluminium cyclone and Door-Oliver plastic cyclone at flow-rate 2.2-1.7 l/min. The respirable dust samples were analysed by x-ray diffraction using NIOSH Method 7500. Even if the results of this study should be considered preliminary, they showed SLC respirable concentrations even many time above TLV-TWA during a sand-blasting activities and some times also during the other activities. Awaiting the correct classification from European Community, it would be desiderable that the workers would had appropriate information and prevention on the specific risks associated to the dust in the construction activities.

Post-traumatic thoracic outlet syndrome (TOS).

TOS is a compressive non-tumorous syndrome of the brachial plexus. It is possible, however, to consider as TOS the irritative and lesional plexus syndrome following trauma as long as compression (or traction) on the nerves is triggered by long-lasting pathological changes of the area after trauma. Overload work of judges and lawyers after traffic accidents does not help to remind the real victim's problem, that is stretching of the neck soft tissues during head acceleration-extension. This movement is due to a forward acceleration. Both the car and the victim's trunk are violently pushed forward while the head does not move fast enough so that it is actually pushed backwards. The mandibula is even slower than the head and this leads to an opening of the mouth with possible temporomandibular joint (TMJ) dislocation. If there is nothing stopping the neck extension, like an appropriate headrest, the momentum is only resisted by cervical soft tissue stretching. Prolonged antalgic contracture and motor neglect may contribute to connective tissue changes and development of microadherences. Final result is fibrosis of paraneurium. The pain-immobility-fibrosis loop is of basic importance in the development of this syndrome.

Entrapment of crural branches of the common peroneal nerve.

Failed back surgery syndrome (FBSS) occurs in 30% of operated patients and represents a heavy problem both regarding disability and costs in first world countries. Among FBSS we found the possibility of a double crush syndrome: a disco-radicular conflict and a peripheral nerve entrapment. The latter, disguised by root compression symptoms, becomes evident only after spinal surgery. Clinical features are the same as for the restless leg syndrome. We found peroneal nerve crural branches entrapped where they crossed the fascia to reach the subcutaneous layer. Venous stasis during immobility caused presentation of symptoms. Neurolysis was performed, all cases were successful. Most of the patients were found to have myofascial pain syndrome (MPS). MPS patients "feel" entrapments more frequently than others not because of their specific pain tolerance but because they are more prone to develop them.

TOS pathophysiology and clinical features.

The authors present 280 patients operated on for thoracic outlet syndrome (TOS). In a first group of patients anatomical variants were the striking findings. The underlying factor for TOS development is therefore a well defined structural condition and its pathogenetic mechanism is known to be a nerve fibre compression. In a second group there was no specific salient finding but a postural deviation. The unique pathological features were adhesions of the brachial plexus to the scalenus muscle. Consequently its pathogenetic mechanism is generally recognized as nerve fibre distraction. In all patients neurological, vascular and myofascial pain symptoms were observed before the operation. Neurological and vascular pain disappeared after surgery, while the myofascial pain remained. The authors believe that especially in the second, larger group of patients enhancement of the pain-immobility-fibrosis loop is the central pathogenetic factor on which surgical therapy is successful, and that myofascial hemisyndrome--probably arising from a long-standing postural deviation--is not a TOS dependent symptom. In TOS, therefore, there is a pain loop that cannot be resolved by surgical therapy alone. The connection between myofascial pain syndrome and TOS might explain the many controversial opinions regarding frequency, results and surgical possibilities of this lesion.

Peripheral papillary tumor of type-II pneumocytes: a rare neoplasm of undetermined malignant potential.

Peripheral papillary adenomas of the lung are uncommon neoplasms (only ten cases have been described so far in the English literature) composed predominantly of type-II pneumocytes and generally considered benign. We describe here two additional cases of this lung tumor. In both cases histological examination revealed an encapsulated papillary neoplasm with invasion of the capsule and, in one case, invasion of the adjacent alveoli and visceral pleura too. The proliferative index (Ki67) was less than 2% and the epithelial cells were positive for cytokeratins, surfactant apoproteins (SP), and nuclear thyroid transcription factor-1 (TTF- 1). Ultrastructurally, the epithelial cells showed the characteristic surface microvilli and cytoplasmic lamellar inclusions of type-II cells. Review of the literature has revealed two other cases of peripheral papillary adenoma of type-II pneumocytes with infiltrative features. Thus, we propose replacing the term peripheral papillary adenoma with peripheral papillary tumor of undetermined malignant potential.

Endoscopic laser ablation as palliative treatment of endobronchial, nonresectable, or recurrent lung cancer: assessment of its impact on quality of life.

Laser ablation (LA) is currently used in our institute as palliative treatment for endobronchial nonresectable or recurrent lung cancer. The objective of this study was to assess the impact of LA on the quality of life (QOL) in a large group of patients with endobronchial obstructions due to nonresectable or re-current lung cancer. Evaluation was based on Eastern Cooperative Oncology Group performance status (ECOG PS) for the "objective" assessment of QOL and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 version 1.0 (EORTC QLQ-C30(v1)) for the "subjective" assessment of QOL. From May 1994 to June 1997, 133 LAs were performed using neodymium: yttrium-aluminum garnet (Nd:YAG) laser at low power settings (< 30W) on 89 evaluable patients (Male/Female 78/11, mean age 63.5/62.8 years, range 42-82/47-73). The QOL was evaluated by ECOG PS and QLQ-C30(v1) at baseline (3 days before LA), t1 (7 days after LA), and t2 (1 month after LA). The objective tumor response was evaluated at t2. The objective tumor response to LA intervention was "excellent," ie, complete response (CR), in 33 (24.8%) patients and "fair," ie, partial response (PR), in 97 (72.9%) patients, with an overall response rate (ORR) of 97.7%. A highly significant decrease in high score (ECOG PS 3-4) was registered from baseline to t1 and from t1 to t2. However, at the same time a significant increase of low score (ECOG PS 0-2) was observed. The comparison of patient QOL assessment by QLQ-C30(v1) at different times during the study was also made; the functioning scales, the global QOL scale, and the symptom scales/items showed a highly significant improvement at t1 compared to baseline (P < 0.001), whereas only global QOL improved at t2 compared to t1. A comparison of baseline ECOG PS scale with QLQ-C30(v1) scale revealed a strong relationship between PS and the symptom "fatigue." Our study demonstrates that dramatic clinical improvement obtained by an effective though palliative treatment such as LA improves QOL based on both physician-rated (PS) and mostly self-rated (QLQ-C30(v1)) assessment.

[Assessment of exposure to ceramic fibers during insulation operations in a thermoelectric power plant]. / Valutazione dell'esposizione a fibre ceramiche durante la coibentazione degli impianti di una centrale termoelettrica in costruzione.

Refractory ceramic fibre concentrations were measured during renewal of the insulation lining of a turbine located in a large power plant. Personal and stationary samples were collected during operations, which involved installing and ripping out standard and pre-coated and pre-shaped ceramic fibre blankets. Operation-length average (OLA) and TWA exposure levels were about 500 F/l and about 100 F/l, respectively, for installing and ripping out operations where non-coated blankets were handled. In these cases specific task-associated personal exposure levels up to 1000 F/l were measured. Personal exposure levels up to as much as 10 times lower were observed in operations involving pre-coated and pre-shaped blankets. The average concentration levels from area samples were always lower than those from personal samples, and showed a downward gradient with the distance from the source. Given the current carcinogenic classification of refractory ceramic fibres (class 2, European), the necessity is stressed of introducing adequate working practices and control measures (adoption of pre-coated and pre-shaped fibrous materials whenever possible, confinement of working area, use of local air extractions ventilation with HEPA filter unit, use of garments for personal protection and respirators, use of wetting or binding liquids prior to removal, quick cleaning of debris from working area), in order to keep the exposure levels and the number of potentially exposed workers to the minimum.