An Infrared Nanospectroscopy Technique for the Study of Electric-Field-Induced Molecular Dynamics.

Static electric fields play a considerable role in a variety of molecular nanosystems as diverse as single-molecule junctions, molecules supporting electrostatic catalysis, and biological cell membranes incorporating proteins. External electric fields can be applied to nanoscale samples with a conductive atomic force microscopy (AFM) probe in contact mode, but typically, no structural information is retrieved. Here we combine photothermal expansion infrared (IR) nanospectroscopy with electrostatic AFM probes to measure nanometric volumes where the IR field enhancement and the static electric field overlap spatially. We leverage the vibrational Stark effect in the polymer poly(methyl methacrylate) for calibrating the local electric field strength. In the relevant case of membrane protein bacteriorhodopsin, we observe electric-field-induced changes of the protein backbone conformation and residue protonation state. The proposed technique also has the potential to measure DC currents and IR spectra simultaneously, insofar enabling the monitoring of the possible interplay between charge transport and other effects.

The transcervical-transparotid corridor for management of parapharyngeal space neoplasms: strengths and limits in a bi-institutional retrospective series.

BACKGROUND AND PURPOSE: Parapharyngeal space (PPS) neoplasms represent 1% of all head and neck tumors and are mostly benign. Surgery is the mainstay of treatment and the transcervical-transparotid (TC-TP) corridor still represents the workhorse for adequate PPS exposure. Our series investigates strengths and limits of this approach on a multi-institutional basis. METHODS: We reviewed consecutive patients submitted to PPS surgery via TC-TP route between 2010 and 2020. Hospital stay, early and long-term complications, and disease status were assessed. RESULTS: One hundred and twenty nine patients were enrolled. Most tumors were benign (79.8%) and involved the prestyloid space (83.7%); the median largest diameter was 4.0 cm. The TC-TP corridor was used in 70.5% of patients, while a pure TC route in about a quarter of cases. Early postoperative VII CN palsy was evident in 32.3% of patients, while X CN deficit in 9.4%. The long-term morbidity rate was 34.1%, with persistent CN impairment detectable in 26.4% of patients: carotid space location, lesion diameter and malignant histology were the main independent predictors of morbidity. A recurrence occurred in 12 patients (9.4%). CONCLUSIONS: The TC-TP corridor represents the benchmark for surgical management of most of PPS neoplasms, though substantial morbidity can still be expected.

Design, Calibration and Morphological Characterization of a Flexible Sensor with Adjustable Chemical Sensitivity and Possible Applications to Sports Medicine.

Active life monitoring via chemosensitive sensors could hold promise for enhancing athlete monitoring, training optimization, and performance in athletes. The present work investigates a resistive flex sensor (RFS) in the guise of a chemical sensor. Its carbon 'texture' has shown to be sensitive to CO2, O2, and RH changes; moreover, different bending conditions can modulate its sensitivity and selectivity for these gases and vapors. A three-step feasibility study is presented including: design and fabrication of the electronic read-out and control; calibration of the sensors to CO2, O2 and RH; and a morphological study of the material when interacting with the gas and vapor molecules. The 0.1 mm-1 curvature performs best among the tested configurations. It shows a linear response curve for each gas, the ranges of concentrations are adequate, and the sensitivity is good for all gases. The curvature can be modulated during data acquisition to tailor the sensitivity and selectivity for a specific gas. In particular, good results have been obtained with a curvature of 0.1 mm-1. For O2 in the range of 20-70%, the sensor has a sensitivity of 0.7 mV/%. For CO2 in the range of 4-80%, the sensitivity is 3.7 mV/%, and for RH the sensitivity is 33 mV/%. Additionally, a working principle, based on observation via scanning electron microscopy, has been proposed to explain the chemical sensing potential of this sensor. Bending seems to enlarge the cracks present in the RFS coverage; this change accounts for the altered selectivity depending on the sensor's curvature. Further studies are needed to confirm result's reliability and the correctness of the interpretation.

A neural network potential with self-trained atomic fingerprints: A test with the mW water potential.

We present a neural network (NN) potential based on a new set of atomic fingerprints built upon two- and three-body contributions that probe distances and local orientational order, respectively. Compared with the existing NN potentials, the atomic fingerprints depend on a small set of tunable parameters that are trained together with the NN weights. In addition to simplifying the selection of the atomic fingerprints, this strategy can also considerably increase the overall accuracy of the network representation. To tackle the simultaneous training of the atomic fingerprint parameters and NN weights, we adopt an annealing protocol that progressively cycles the learning rate, significantly improving the accuracy of the NN potential. We test the performance of the network potential against the mW model of water, which is a classical three-body potential that well captures the anomalies of the liquid phase. Trained on just three state points, the NN potential is able to reproduce the mW model in a very wide range of densities and temperatures, from negative pressures to several GPa, capturing the transition from an open random tetrahedral network to a dense interpenetrated network. The NN potential also reproduces very well properties for which it was not explicitly trained, such as dynamical properties and the structure of the stable crystalline phases of mW.

Molecular Biology and Therapeutic Targets of Primitive Tracheal Tumors: Focus on Tumors Derived by Salivary Glands and Squamous Cell Carcinoma.

Primary tracheal tumors are rare, constituting approximately 0.1-0.4% of malignant diseases. Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) account for about two-thirds of these tumors. Despite most primary tracheal cancers being eligible for surgery and/or radiotherapy, unresectable, recurrent and metastatic tumors may require systemic treatments. Unfortunately, the poor response to available chemotherapy as well as the lack of other real therapeutic alternatives affects the quality of life and outcome of patients suffering from more advanced disease. In this condition, target therapy against driver mutations could constitute an alternative to chemotherapy, and may help in disease control. The past two decades have seen extraordinary progress in developing novel target treatment options, shifting the treatment paradigm for several cancers such as lung cancer. The improvement of knowledge regarding the genetic and biological alterations, of major primary tracheal tumors, has opened up new treatment perspectives, suggesting the possible role of biological targeted therapies for the treatment of these rare tumors. The purpose of this review is to outline the state of knowledge regarding the molecular biology, and the preliminary data on target treatments of the main primary tracheal tumors, focusing on salivary-gland-derived cancers and squamous cell carcinoma.

Management of parapharyngeal space tumors with transparotid-transcervical approach: analysis of prognostic factors related with disease-control and functional outcomes.

PURPOSE: Different therapeutic strategies have been developed to improve surgical and functional outcome of parapharyngeal space (PPS) neoplasms. The transparotid-transcervical approach (TTa) is a valid surgical option to manage most PPS tumors. Its short- and long-term disease control and cranial nerve (c.n.) function outcomes have not been discussed extensively. METHODS: All patients who underwent TTa over a 10-year period at a tertiary academic center were retrospectively reviewed. Data about preoperative imaging, clinical presentation, tumor's size, location and histology, and postoperative oncological and functional results were registered and analyzed. RESULTS: Sixty patients matched the inclusion criteria. Most of the lesions were benign (71.7%), involved the prestyloid PPS (63.3%) and measured more than 30 mm (75%). Fifty-two (86.7%) lesions were resected en-bloc. Clear margins were achieved in 91.7% of the cases, with positive margins solely associated with malignancy (p = 0.008). Post-operative c.n. function was satisfactory, with X c.n. function significantly associated with the retrostyloid location (p = .00) and neurogenic tumors (p = 0.02). Local disease-control was achieved in 96% of the cases after a median follow-up of 46 (± 19.7-82.0 IQR) months. CONCLUSIONS: The TTa was safe and effective, achieving a satisfactory local control rate. Nevertheless, malignancies maintain a higher rate of positive margin due to their infiltrative nature and the complex anatomy of the PPS. In such cases, multiportal approaches might be more effective. However, post-operative c.n. function remained satisfactory, irrespective of lesions' size and histopathologic behavior. A higher X c.n. deficit rate was observed in retrostyloid and neurogenic lesions.

Employment uncertainty and fertility intentions: Stability or resilience?

The role of employment uncertainty as a fertility driver has previously been studied with a limited set of constructs, leading to inconclusive results. We address this oversight by considering perceived stability of employment and perceived resilience to potential job loss as two key dimensions of employment uncertainty in relation to fertility decision-making. The present study relies on the 2017 Italian Trustlab survey and its employment uncertainty module. We find that perception of resilience to job loss is a powerful predictor of fertility intentions, whereas perception of employment stability has only a limited impact. The observed relationship between resilience and fertility intentions is robust to the inclusion of person-specific risk attitude and does not depend on the unemployment rate or the share of fixed-term contracts in the area of residence. We conclude that the notion of employment uncertainty includes distinct expectations towards the future, which should be considered separately to understand fertility decision-making.Supplementary material for this article is available at: https://doi.org/10.1080/00324728.2021.1939406.

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults.

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.

Salvage neck dissection for isolated neck recurrences in head and neck tumors: Intra and postoperative complications.

BACKGROUND AND OBJECTIVES: The current evidence regarding complications after salvage neck dissection (ND) for isolated regional recurrences (IRRs) in head and neck cancers is poor. The aim of this study is to evaluate the incidence and differences in complication rates of salvage ND after primary surgery, radiotherapy, chemoradiotherapy, or combined treatments. METHODS: This was a multicentric retrospective study on 64 patients who underwent salvage ND for IRR in three Italian institutes between 2008 and May 2020. RESULTS: Complications were detected in 7 of the 34 patients (20.8%) and surgeons described difficult dissection in 20 patients (58.82%). Accidental vascular ligations or nervous injury during surgery were never detected. None of the variables analyzed were statistically significant in predicting the risk of complications, disease-free survival, or overall survival. CONCLUSIONS: IRR represents a rare entity among total relapses. The incidence of complications after salvage ND for IRR is higher than after primary surgery but at an acceptable rate in experienced hands. However, an adequate balance between functional and oncological outcomes is mandatory.

Second primary tumors in head and neck cancer patients: The importance of a "tailored" surveillance.

OBJECTIVE: Head and neck cancer survivors have increased risk of developing second primary tumors compared to overall population. Because second primary represents a major cause of morbidity and mortality in this population, early detection is fundamental. MATERIALS AND METHODS: In this 10-year single-institution study, we investigated the following: incidence, clinical-pathological risk factors, and survival of patients with second primary tumor. We included all patients with diagnosis of squamous cell carcinoma of the head and neck seen at the Modena University Hospital from 2008 to 2018. RESULTS: Among 1,177 patients included, 222 (18.9%) developed second primary tumor; its survival probability at 5 years was 40.6%. Alcohol consumption (p = .0055) and index cancer in oropharynx (p = .0029), supraglottic larynx (p = .0000), glottic larynx (p = .0222) were associated with higher risk of second primary. The most common second primary sites were head and neck district and lung (70, 31.5%, and 67, 30.2%, respectively). Head and neck district were more common in oral cavity (18, 43%) and oropharynx index cancer (20, 31%); lung second primary in hypopharynx (4, 40%), supraglottic larynx (17, 43%), and glottic larynx index cancer (23, 35%). CONCLUSION: Head and neck cancer survivors developing a second primary tumor have dismal prognosis. Tailored surveillance is recommended.

Surgical management of benign cervical tracheoesophageal fistulas: A single-tertiary academic institution experience.

PURPOSE: Despite improvements of diagnosis and management, acquired benign tracheoesophageal fistulas (AB-TEFs) remain a challenging clinical problem and a life-threating condition. In the present study, we reviewed the early results and the long-term outcomes after surgical treatment of cervical AB-TEFs treated in our institution during the last 9 years. METHODS: This retrospective study included patients who underwent transcervical repair of benign cervical AB-TEFs. Patients were identified from a prospectively filled electronic database which included patients' demographics, medical history, disease presentation, prior treatments, operative report, morbidity and mortality, hospital stay, postoperative results and follow-up information. RESULTS: A total of 13 patients affected by cervical AB-TEF were treated. Most of the patients (91%) in our series were treated with a lateral cervicotomic approach with interposition of either sternocleidomastoid muscle flap (72.7%) or pectoralis major myocutaneous flap (9.1%) or infrahyoid muscle flap (9.1%). The univariate analysis of showed that the etiology and surgical technique were significantly associated with immediate postoperative outcome. Esophageal diversion was removed in all patients but 3 due to their neurological status, which was the only significant factor related to post-operative oral-intake (p =0.016). We experienced 2 (18.2%) failures of the reconstruction, which occurred in patients previously treated with chemoradiation for head and neck malignancies. None of the remaining patients (72.8%) relapsed after a long-term follow-up restoring a normal oral diet was restored. CONCLUSION: The lateral cervicotomic approach with sternocleidomastoid flap interposition showed its effectiveness and safety in the treatment of AB-TEFs in our single-institution experience.

Prelaminated flaps in head and neck cancer reconstructive surgery: A systematic review.

BACKGROUND: Prelamination is a reconstructive technique providing fasciomucosal or composite flaps with low donor-site morbidity. We conducted a systematic review of retrospective studies to assess the application of prelaminated flaps in reconstructive surgery of head and neck cancer patients, and to evaluate the advantages and disadvantages of this technique. METHODS: This systematic review adhered to the recommendations of the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-analysis) 2009 guidelines. A computerized MEDLINE search was performed using the PubMed service of the U.S. National Library of Medicine (www.pubmed.org) and Scopus database (www.scopus.com), running the following search string: "prelamination OR prelaminated AND flap." Two authors screened the articles, then selected and extracted data on malignancies characteristics, reconstructive techniques, outcomes and complications. RESULTS: A total of 19 articles were selected and reviewed from 128 identified. Seven of 19 articles were case reports, 12 articles were case series. One-hundred-two patients underwent reconstructive treatment by prelamination technique using a wide variety of flaps (92 free, 10 pedicled). The sites of reconstruction were oral cavity (66 floor of the mouth, 3 retromolar trigone, 6 hard palate, 4 cheek, 4 tongue), 8 facial skin (5 of them sited on the nose), 4 oropharyngeal defects, 1 laryngotracheal region. No case of total flap loss was reported. Partial flap loss or shrinkage requiring minor surgical revisions was observed in 18 patients (17.6%). Primary closure of the donor site was achieved in 97 cases (97%) and 3 (3%) required revision surgery of the donor site. CONCLUSION: Prelamination is an effective and versatile technique, with low donor-site morbidity. Further studies would be needed to investigate the impact on the patient's oncologic outcome. More comparative studies with standard reconstructive techniques are essential to understand when it is worth performing this sophisticated procedure.

Waveguide-integrated niobium- nitride detectors for on-chip quantum nanophotonics.

NbN-based detectors can detect light from the granular regime (single or few photons) up to weak continuous photon fluxes at wavelengths ranging from visible light up to mid-IR. The article reports our recent results on a novel linear detector, the waveguide-integrated hot electron bolometer (HEB) capable to measure photon fluxes of large coherent beams in a regime in which superconducting nanowire single photon detectors (SNSPDs) are not efficient due to their strong nonlinearity. SNSPDs, photon number resolving detectors and amplitude multiplexing readout schemes, all integrated on photonic circuits are also discussed in the paper. The compatibility of the integrated HEB detectors with the SNSPDs technology can allow the characterization of complex non classical states of light within the same chip.

Tracheostomy in the COVID-19 pandemic.

PURPOSE: The role of tracheostomy in COVID-19-related ARDS is unknown. Nowadays, there is no clear indication regarding the timing of tracheostomy in these patients. METHODS: We describe our synergic experience between ENT and ICU Departments at University Hospital of Modena underlining some controversial aspects that would be worth discussing tracheostomies in these patients. During the last 2 weeks, we performed 28 tracheostomies on patients with ARDS due to COVID-19 infection who were treated with IMV. RESULTS: No differences between percutaneous and surgical tracheostomy in terms of timing and no case of team virus infection. CONCLUSION: In our experience, tracheostomy should be performed only in selected patients within 7- and 14-day orotracheal intubation.

The impact of gynecologists' conscientious objection on abortion access.

Although abortion in Italy is free of charge and legal in a broad set of circumstances, 71% of gynecologists are registered as conscientious objectors, i.e. they are exempted from performing abortions for reasons of religious or moral beliefs. To assess whether this practice limits abortion access, we analyze aggregate regional data on abortion and a dataset of over one million clinical records of single interventions performed between 2002 and 2016. Results, from both cross-regional panel data and microdata analysis, suggest that conscientious objection hampers abortion access at the local level, being a significant driver of a woman's decision of having an abortion out of the region of residence and leading to longer waiting times to have one. Conscientious objection appears to have a stronger impact on women living in lower-income regions or experiencing other forms of economic disadvantage.

Central compartment revision surgery for persistent or recurrent thyroid carcinoma: analysis of survival and complication rate.

PURPOSE: Locoregional recurrence of thyroid carcinoma is relatively common and reported rate are between 5 and 20%. Cervical nodes are usually involved, especially at the central compartment. The management of recurrent thyroid carcinoma at central compartment still remains challenging because of higher incidence of complication rate. The aim of the study is to evaluate the survival and complications rate after revision surgery. METHODS: Retrospective cohort study on a group of patients that underwent revision surgery for persistent or recurrent thyroid carcinoma from January 1, 2003 to December 31, 2017. Survival outcomes were calculated using Kaplan-Meier method. Significant variables on univariate analysis were subjected to a Cox proportional hazards regression multivariate model. RESULTS: Fifty-two patients involved, 22 male (40%) and 30 female (60%). Mean age was 54 years old (range 24-85). Mean follow-up was 79 months, median follow-up was 85 months, with a range between 8 and 153 months. The 5-year overall survival was 90.8% while at 10 years it was 69.8%. The 5-year disease-specific survival was 93.5%, while at 10 years it dropped to 77.9%. The rate of recurrent laryngeal nerve paralysis and persistent hypocalcemia in our series were 1.3% and 5.9%, respectively. No evidence of thoracic duct, esophageal or laryngeal and tracheal injury was found in this case series. Regarding prognostic factors, univariate and multivariate analysis highlighted as statistically significant: the aggressive histological variants, the presence extranodal extension or soft-tissue metastasis. CONCLUSION: The surgical option remains the gold standard in locoregional recurrences of thyroid carcinoma and should be performed by experienced surgeons to reduce postoperative complications.

Chronic and recurrent benign lymphadenopathy without constitutional symptoms associated with human herpesvirus-6B reactivation.

Chronic/recurrent behaviour may be encountered in some distinct atypical or malignant lymphoproliferations, while recurrences are not generally observed in reactive/benign lymphadenopathies. We retrospectively analysed a consecutive series of 486 human immunodeficiency virus-negative adults, who underwent lymphadenectomy. Neoplastic and benign/reactive histopathological pictures were documented in 299 (61·5%) and 187 (38·5%) cases, respectively. Of note, seven of the 111 (6·3%) patients with benign lymphadenopathy without well-defined aetiology, showed chronic/recurrent behaviour, without constitutional symptoms. Enlarged lymph nodes were round in shape and hypoechoic, mimicking lymphoma. Reactive follicular hyperplasia and paracortical expansion were observed. Human herpesvirus (HHV)-6B positive staining in follicular dendritic cells (FDCs) was documented in all seven patients. Serological, molecular and immunological examinations suggested HHV-6B reactivation. Among the remaining 104 cases with reactive lymphoid hyperplasia in the absence of well-known aetiology and without recurrences, positivity for HHV-6B on FDCs was found in three cases, whereas in seven further patients, a scanty positivity was documented in rare, scattered cells in inter-follicular regions. Immunohistochemistry for HHV-6A and HHV-6B was invariably negative on 134 lymph nodes, with either benign pictures with known aetiology or malignant lymphoproliferative disorders, tested as further controls. Future studies are warranted to investigate a potential association between HHV-6B reactivation and chronic/recurrent benign lymphadenopathy.

Photon-counting and analog operation of a 24-pixel photon number resolving detector based on superconducting nanowires.

We investigate the transition from the photon-counting to the linear operation mode in a large-dynamic range photon-number-resolving-detector (PNRD). A 24-pixel photon-number-resolving-detector, based on superconducting nanowires in a series configuration, has been fabricated and characterized. The voltage pulses, generated by the pixels, are summed up into a single readout pulse whose height is proportional to the detected photon number. The device can resolve up to twenty-five distinct output levels corresponding to the detection of n = 0-24 photons. Due to its large dynamic range, high sensitivity, high speed and wide wavelength range, this device has potential for linear detection in the few tens of photons range. We show its application in the detection of analog optical signals at frequencies up to few hundred MHz and investigate the limits related to the finite number of pixels and to the pixel's dead time.

Atypical mycobacteriosis involving parotid and para-retropharyngeal spaces.

The incidence of retro-parapharyngeal localization of cervical adenitis due to non-tuberculous mycobacteria is very rare. We present a case of an 18-months-old child with an involvement of parapharyngeal and retropharyngeal areas, right parotid and submandibular regions by atypical mycobacteriosis in the CT and MRI scan. The masses were surgically removed and the frozen-section histological exam upheld their atypical mycobacterial origin.