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Introduction: Purpose of our study was to compare two competing methods of performing bisyllabic word speech audiometry for the detection of the 50% speech reception threshold in noise (SRT50)., Methods: Classic method is performed submitting multiple word lists at a fixed signal-to-noise ratio. A newer Fast method - Italian Fast Speech Reception Threshold 50 (IFastSRT50) - is performed by means of program software with a single list of bisyllabic words and noise intensity shifting., Results: Means comparison between SRT50 Classic and IFastSRT50 shows a slight significant correlation (r = 0.263; p = 0.044) and a wide significant difference: SRT50 Classic = -2.763 dB (SD = 4.1) and IFastSRT50 = -7.803 dB (SD = 2.1) (p < 0.0001). There is a high difference between the test execution time means (SRT50 Classic = 11 min, IFastSRT50 = 2 min; p < 0.0001). The correlation between test results and execution times was higher for SRT50 Classic than IFastSRT50., Conclusion: IFastSRT50 test is a reliable method to quickly investigate signal-to-noise ratio needed to obtain 50% of recognition scores with bisyllabic words; it allows less execution time than SRT50 Classic method and can avoid patient fatigue and other limitations of different speech discrimination tests in noise as sentences based ones., (© 2024 S. Karger AG, Basel.)

Background: Volumetric Muscle Loss (VML), resulting from severe trauma or surgical ablation, is a pathological condition preventing myofibers regeneration, since skeletal muscle owns the remarkable ability to restore tissue damage, but only when limited in size. The current surgical therapies employed in the treatment of this pathology, which particularly affects military personnel, do not yet provide satisfactory results. For this reason, more innovative approaches must be sought, specifically skeletal muscle tissue engineering seems to highlight promising results obtained from preclinical studies in VML mouse model. Despite the great results obtained in rodents, translation into human needs a comparable animal model in terms of size, in order to validate the efficacy of the tissue engineering approach reconstructing larger muscle mass (human-like). In this work we aim to demonstrate the validity of a porcine model, that has underwent a surgical ablation of a large muscle area, as a VML damage model., Results: For this purpose, morphological, ultrasound, histological and fluorescence analyses were carried out on the scar tissue formed following the surgical ablation of the peroneus tertius muscle of Sus scrofa domesticus commonly called mini-pig. In particular, the replenishment of the damaged area, the macrophage infiltration and the vascularization at different time-points were evaluated up to the harvesting of the scar upon six months., Conclusion: Here we demonstrated that following VML damage, there is an extremely poor regenerative process in the swine muscle tissue, while the formation of fibrotic, scar tissue occurs. The analyses performed up to 180 days after the injury revealed the development of a stable, structured and cellularized tissue, provided with vessels and extracellular matrix acquiring the status of granulation tissue like in human., (© 2023. The Author(s).)

In human dystrophies, progressive muscle wasting is exacerbated by ectopic deposition of fat and fibrous tissue originating from fibro/adipogenic progenitors (FAPs). In degenerating muscles, the ability of these cells to promote successful healing is attenuated, and FAPs aberrantly expand and differentiate into adipocytes and fibroblasts. Thus, arresting the fibro/adipogenic fate of FAPs, without affecting their physiological role, represents a valuable therapeutic strategy for patients affected by muscle diseases. Here, using a panel of adipose progenitor cells, including human-derived FAPs, coupled with pharmacological perturbations and proteome profiling, we report that LY2090314 interferes with a genuine adipogenic program acting as WNT surrogate for the stabilization of a competent β-catenin transcriptional complex. To predict the beneficial impact of LY2090314 in limiting ectopic deposition of fat in human muscles, we combined a poly-ethylene-glycol-fibrinogen biomimetic matrix with these progenitor cells to create a miniaturized 3D model of adipogenesis. Using this scalable system, we demonstrated that a two-digit nanomolar dose of this compound effectively represses adipogenesis at higher 3D scale, thus indicating the potential for LY2090314 to limit FAP-derived fat infiltrates in dystrophic muscles., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Aging is a physiological and progressive phenomenon in all organisms' life cycle, characterized by the accumulation of degenerative processes triggered by several alterations within molecular pathways. These changes compromise cell fate, resulting in the loss of functions in tissues throughout the body, including the brain. Physiological brain aging has been linked to structural and functional alterations, as well as to an increased risk of neurodegenerative diseases. Post-transcriptional RNA modifications modulate mRNA coding properties, stability, translatability, expanding the coding capacity of the genome, and are involved in all cellular processes. Among mRNA post-transcriptional modifications, the A-to-I RNA editing, m6A RNA Methylation and Alternative Splicing play a critical role in all the phases of a neuronal cell life cycle and alterations in their mechanisms of action significantly contribute to aging and neurodegeneration. Here we review our current understanding of the contribution of A-to-I RNA editing, m6A RNA Methylation, and Alternative Splicing to physiological brain aging process and neurodegenerative diseases., Competing Interests: Declaration of competing interests All the authors declare no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Three-dimensional (3D) bioprinting is an emerging technology, which turned out to be an optimal tool for tissue engineering approaches. To date, different printing systems have been developed. Among them, the extrusion-based approach demonstrated to be the most suitable for skeletal muscle tissue engineering, due to its ability to produce and deposit printing fibers in a parallel pattern that well mimic the native skeletal muscle tissue architecture. In tissue bioengineering, a key role is played by biomaterials, which must possess the key requisite of 'printability'. Nevertheless, this feature is not often well correlated with cell requirements, such as motives for cellular adhesion and/or absorbability. To overcome this hurdle, several efforts have been made to obtain an effective bioink by combining two different biomaterials in order to reach a good printability besides a suitable biological activity. However, despite being efficient, this strategy reveals several outcomes limitations. We report here the development and characterization of a novel extrusion-based 3D bioprinting system, and its application for correction of volumetric muscle loss (VML) injury in a mouse model. The developed bioprinting system is based on the use of PEG-Fibrinogen, a unique biomaterial with excellent biocompatibility, well-suited for skeletal muscle tissue engineering. With this approach, we obtained highly organized 3D constructs, in which murine muscle progenitors were able to differentiate into muscle fibers arranged in aligned bundles and capable of spontaneously contracting when cultured in vitro . Furthermore, to evaluate the potential of the developed system in future regenerative medicine applications, bioprinted constructs laden with either murine or human muscle progenitors were transplanted to regenerate the Tibialis Anterior muscle of a VML murine model, one month after grafting., (Creative Commons Attribution license.)

The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked to CD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice from subcutaneous growth of MDA-MB-468 BC cells. RNAseq analysis identified a 42 gene fingerprint predicting BC cell sensitivity and favorable outcomes in advanced BC. ICAM1 was a major regulator of CD32-CR T cell-mediated cytotoxicity. CD32-CR T cells may help identify cell surface CD32 ligand(s) and novel prognostically relevant transcriptomic signatures and develop innovative BC treatments., (© 2022 Sconocchia et al.)

Purpose: To present a case of a woman referred for the management of displacement of one implant in her right posterior mandible that had occurred three days previously., Materials and Methods: After implant placement, the practitioner was no longer able to detect the implant and inserted a second one at the same site without taking a control radiograph. At the end of surgery, when a radiograph was finally taken, the first implant appeared displaced into the mandible body. The patient suffered total paresthesia on the right lower lip and chin. A flap was raised and bone osteotomies were performed on the lateral side of the mandible to create a rectangular cortical bone window that was removed. The implant was stuck by the second implant placed coronally, and only after unscrewing this second implant was it possible to remove the first one., Results: After 18 months, the patient recovered full sensitivity., Conclusions: In cases of implant displacement, it is always recommended that appropriate radiographs are performed to visualise where the implants could have been displaced in order to avoid more serious consequences., Competing Interests: The authors declare no financial relationships and therefore no conflict of interest.

Poly(ADP-ribose)polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a group of new potent PARP-1 inhibitors, acyl-piperazinylamides of 3-(4-oxo-3,4-dihydro-quinazolin-2-yl)-propionic acid. Molecular modeling studies highlighted the preponderant role of the propanoyl side chain., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To study the effects of antiepileptic treatment on sleep parameters and video-polysomnography (VPSG) seizures in nocturnal frontal lobe epilepsy (NFLE)., Methods: Twenty patients with a clinical and VPSG diagnosis of NFLE (baseline polysomnography [PSG]) underwent a clinical follow-up and performed a second VPSG after effective antiepileptic treatment lasting for at least 6 months. Conventional sleep measures, cyclic alternating pattern (CAP) parameters, and objective VPSG seizures were assessed in NFLE patients before and after treatment and were compared with the results of 20 age- and gender-matched control subjects., Results: Antiepileptic treatment determined a partial reduction of objective VPSG seizures of approximately 25% compared to baseline condition. Alterations of most conventional sleep measures recovered normal values, but nonrapid eye movement (NREM) sleep instability remained pathologically enhanced (CAP rate, +26% compared to controls) and was associated with persistence of daytime sleepiness., Conclusions: Residual epileptic events and high levels of unstable NREM sleep can define a sort of objective resistance of both seizures and disturbed arousal system to the therapeutic purpose of the antiepileptic drugs in NFLE. This finding could determine the need for new therapeutic options in this particular form of epilepsy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Atypical cardiorespiratory patterns can be found during routine clinical use of portable monitoring for diagnosis of sleep-disordered breathing (SDB). Over 1,000 consecutive portable recordings were analysed to study the potential ictal nature of stereotyped cardiorespiratory and motor patterns. Snoring, airflow, thoracic effort, pulse rate, body position, oxygen saturation and activity of the anterior tibialis muscles were quantified. Recordings showing stereotyped polygraphic patterns recurring throughout the night, but without the features of sleep apnoea (apnoea/hypopnoea index <5 events·h(-1)), were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography. A total of 15 recordings showing repeated polygraphic patterns characterised by a sequence of microphone activation, respiratory activity atypical for sleep and wakefulness, heart rate acceleration and limb movements, followed by body position change, were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography that showed frontal epileptic discharges triggering periodic electroencephalographic arousals, autonomic activation and stereotyped motor patterns. A diagnosis of nocturnal frontal lobe epilepsy (NFLE) was established for all patients. NFLE should be taken into consideration in patients with stereotyped and recurrent behavioural features during portable monitoring carried out for diagnosis of SDB.

Pitt-Hopkins syndrome is a rare genetic form of severe psychomotor delay, caused by mutations in transcription cell factor-4 gene and characterized by distinctive dysmorphic features and abnormal breathing pattern. The current report describes the polygraphic features of the syndrome's typical breathing pattern in a patient both in wakefulness and in sleep. The control of these breathing alterations is important to prevent the neurological sequelae linked to chronic cerebral hypoxemia in early ages. No data are available on effective treatment options for breathing abnormalities of Pitt-Hopkins syndrome. The authors polygraphically documented a reduction of apneic and hypopneic phenomena, with a significant improvement in saturation values, after the introduction of sodium valproate.

Purpose: To describe the polysomnographic features and distribution of epileptic motor events, in relation to conventional sleep measures and cyclic alternating pattern (CAP) parameters, in 40 untreated patients with nocturnal frontal lobe epilepsy (NFLE)., Methods: We analyzed the basal polysomnographic recordings of 40 patients (20 male and 20 female; mean age: 31 ± 10 years) with a diagnosis of nocturnal frontal lobe epilepsy. Conventional sleep measures and CAP parameters were assessed. Polysomnographic recordings were subdivided in sleep cycles. The distribution of the epileptic motor events (including minor motor events, paroxysmal arousals, tonic-dystonic, or hyperkinetic seizures and epileptic nocturnal wandering) was analyzed throughout: total sleep time, non-rapid eye movement (NREM) and REM sleep, light sleep (S1 + S2), slow wave sleep (SWS), each sleep cycle, CAP or non-CAP sleep, phase A and phase B of CAP. Only clear epileptic motor events supported by video-polysomnographic evidence were taken into consideration. Polysomnographic findings of patients with NFLE were compared with those of 24 age- and gender-balanced healthy subjects without sleep complaints., Key Findings: Compared to controls, patients with NFLE showed a significant increase in wake after sleep onset, SWS duration, and REM latency, whereas REM sleep duration was significantly lower in NFLE patients. The patients with NFLE showed a significant increase of CAP time, CAP rate (72% vs. 32% in control group), CAP cycles, and mean duration of a CAP sequence. These findings were associated with a significant enhancement of all subtypes of the A phases of CAP (mainly subtype A1). A total of 139 epileptic motor events supported by video-polysomnographic evidence were counted: 98% of all seizures occurred in NREM sleep and 72% of NREM seizures emerged from SWS, the latter being particularly collected in the first sleep cycles and decreasing in frequency together with the progressive decline of deep sleep. Ninety percent of total NREM seizures occurred during a CAP sequence, and CAP-related seizures occurred in association with a phase A., Significance: Significant polysomnographic alterations seem to emerge in patients with NFLE (increased REM latency, epileptic fragmentation of SWS, and increase of CAP rate). The analysis of seizure distribution showed that most epileptic events occurred in SWS, with predominance in the first sleep cycle and decreasing in frequency together with the homeostatic decline of SWS across the night. Within the NREM sleep, CAP is a manifestation of unstable sleep and represents a powerful predisposing condition for the occurrence of nocturnal motor seizures, which arise in concomitance with a phase A., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

In this paper, we have evaluated the diagnostic utility of three antigenic regions of the Mycoplasma pneumoniae P1, P30, and MPN456 gene products in order to replace the soluble, whole-cell bacterial extract in serological assays. Antigenic regions, being previously identified as B-cell epitopes, were used individually or assembled in a recombinant chimeric antigen by genetic engineering. Paired serum samples from 47 patients with M. pneumoniae infection and from 39 subjects with a clinical picture of atypical pneumonia but without a defined diagnosis of M. pneumoniae infection were included. Immunoglobulin G (IgG) antibodies against epitopes carried by recombinant antigens were measured by performing recombinant enzyme-linked immunosorbent assays (Rec-ELISAs). Rec-ELISA results were compared to those obtained by a commercial assay using the whole-cell Mycoplasma antigen. Our study demonstrates that all IgG Rec-ELISAs using recombinant antigens have better sensitivity with respect to the commercial assay. Furthermore, we show that the use of chimeric antigens improve the performance of the assays. The use of recombinant antigens is effective in distinguishing M. pneumoniae-infected patients from uninfected individuals and shows that immunoassays based on recombinant antigens could provide the basis for standardized commercial tests for the serodiagnosis of M. pneumoniae diseases.

Objective: The relationship between CAP parameters and subjective time perception during sleep in primary insomnia was investigated., Patients and Methods: Data collected from all-night PSG recordings of 20 patients with a diagnosis of paradoxical insomnia (misperceptors) were compared with those of 20 normal gender- and age-matched subjects (controls). Besides sleep staging, scoring measures included CAP parameters and EEG arousals., Results: Patients and controls presented non-significant differences in the amounts of objective sleep time (464 min vs. 447 min) and objective sleep latency (9 min vs. 8 min). Compared to controls, misperceptors reported a significantly shorter time of perceived sleep (285 min vs. 461 min) and a significantly longer duration of perceived sleep latency (51 min vs. 22 min). In spite of the 11 objective awakenings, misperceptors reported only 4 subjective awakenings, while controls described 2 of the 5 objective awakenings. Arousal index (31.7/h vs. 18.6/h) and total CAP rate (58.1% vs. 35.5%) were significantly higher in misperceptors. In the sleep period between objective and subjective sleep onset, CAP rate was 64.4% in misperceptors and 45.1% in controls (p<0.002). Insomniacs showed significantly higher amounts of CAP rate in stage 1 (62.7% vs. 37.5%) and in stage 2 (53.3% vs. 33.1%), but not in slow wave sleep. CAP phase A2 subtypes were significantly increased in misperceptors (31% vs. 24%)., Conclusions: The study points out the topical role of enhanced activation and arousal instability not only in the first part of the night (mismatch between objective and subjective sleep onset) but also in the misperception of consecutive objective awakenings which are subjectively grouped together as a single prolonged event.

Mycoplasma pneumoniae is the leading cause of atypical pneumonia in children and young adults. Bacterial colonization can occur in both the upper and the lower respiratory tracts and take place both endemically and epidemically worldwide. Characteristically, the infection is chronic in onset and recovery and both humoral and cell-mediated mechanisms are involved in the response to bacterial colonization. To identify bacterial proteins recognized by host antibody responses, a whole-genome M. pneumoniae library was created and displayed on lambda bacteriophage. The challenge of such a library with sera from individuals hospitalized for mycoplasmal pneumonia allowed the identification of a panel of recombinant bacteriophages carrying B-cell epitopes. Among the already known M. pneumoniae B-cell antigens, our results confirmed the immunogenicity of P1 and P30 adhesins. Also, the data presented in this study localized, within their sequences, the immunodominant epitopes recognized by human immunoglobulins. Furthermore, library screening allowed the identification of four novel immunogenic polypeptides, respectively, encoded by fragments of the MPN152, MPN426, MPN456 and MPN-500 open reading frames, highlighting and further confirming the potential of lambda display technology in antigen and epitope discovery.

Background and Purpose: Treatment of chronic insomnia with nightly hypnotics is efficacious, but discontinuation is recommended after 1 month, less than the average disease duration. This study was undertaken to determine the efficacy of intermittent administration., Patients and Methods: A double-blind study was carried out on 8 patients (age, 32.8 +/- 9 years; 3 men) with primary sleep maintenance insomnia longer than 1 month. Polysomnography of conventional sleep parameters, cyclic alternating patterns (CAPs), and arousals was performed. Perception of sleep quality was assessed on a visual analog scale. After an adaptation night, baselines were recorded followed by 6 consecutive nights of alternating treatment with zolpidem (10 mg) or placebo., Results: Significant improvements on baseline values (P < 0.0001) were observed on all 3 active treatment nights for total sleep time, sleep efficiency, CAP time, CAP rate, subtype A2, arousals, and arousal index. Deep non-rapid eye movement sleep increased with the second and third doses of active treatment (P < 0.0001). Rapid eye movement sleep increased during the last 3 polysomnographic recordings (P < 0.014). Sleep quality (visual analog scale) improved on all nights after the initial dose of active treatment (P < 0.0001). There was no evidence of rebound insomnia with placebo., Conclusions: Intermittent treatment with zolpidem in primary insomnia patients improves CAP parameters and arousals, as well as sleep duration and quality, in the absence of rebound insomnia.

Background: The IgA1 protease of Streptococcus pneumoniae is a proteolytic enzyme that specifically cleaves the hinge regions of human IgA1, which dominates most mucosal surfaces and is the major IgA isotype in serum. This protease is expressed in all of the known pneumococcal strains and plays a major role in pathogen's resistance to the host immune response. The present work was focused at identifying the immunodominant regions of pneumococcal IgA1 protease recognized by the human antibody response., Results: An antigenic sequence corresponding to amino acids 420-457 (epiA) of the iga gene product was identified by screening a pneumococcal phage display library with patients' sera. The epiA peptide is conserved in all pneumococci and in two out of three S. mitis strains, while it is not present in other oral streptococci so far sequenced. This epitope was specifically recognized by antibodies present in sera from 90% of healthy adults, thus representing an important target of the humoral response to S. pneumoniae and S. mitis infection. Moreover, sera from 68% of children less than 4 years old reacted with the epiA peptide, indicating that the human immune response against streptococcal antigens occurs during childhood., Conclusion: The broad and specific recognition of the epiA polypeptide by human sera demonstrate that the pneumococcal IgA1 protease contains an immunodominant B-cell epitope. The use of phage display libraries to identify microbe or disease-specific antigens recognized by human sera is a valuable approach to epitope discovery.

The purification of soluble fulvic acids (FA) based on a diafiltration technique is carried out on antarctic water and snow samples, characterised by low humic compound content (0.1-0.8 mg/l). Results are compared with those of FA purified with the dialysis technique that, together with ion-exchange resins, performs an often used purification process. With the adopted procedure it is possible to minimise the high content of inorganic salts deriving in part from the isolation method XAD-8 adopted, as shown by FTIR, elemental and thermogravimetric analysis.

The research is intended to get knowledge of some enzymatic activity of Actinomyces Israeli bacteria isolated from the mouth of several subjects and it shows how such bacterium can give rise to erosive phenomena of the enamel of the teeth and also to infections of the periodontal through a process causing the formation of a cloudy halo in the cultures.

Among the many cases of teeth subjected to trauma, this one, that it has been observed, was fit for an attempt of replant for the good possibilities of success; it has been considered the age, very young, of the patient, the good health and principally her good orodental situation. Two radiografies made after short time have revealed the formation of osseus trabeculae, irrefutable sign of taking root.