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Purpose Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a significant recurrence rate. We reviewed our experience with recurrent TBSCCs. Materials and methods Clinicopathological and therapeutic variables potentially associated with disease-free survival (DFS) and disease-specific survival (DSS) were assessed in 17 TBSCC patients who died of their disease after treatment. Results TBSCC recurrences were treated with surgery in 12 cases (palliative in 11, with curative intent in 1) and palliative chemotherapy in 5; the median DFS and DSS were 6 and 16 months, respectively. The mean DFS and DSS were longer in patients who had primary lateral temporal bone resection (LTBR) rather than subtotal temporal bone resection (STBR) (p = 0.0173 and p = 0.03, respectively). Patients given non-surgical palliative treatment for recurrences had a longer mean DSS than those who underwent surgery (trend toward significance, p = 0.09). Conclusions Our results reflect the aggressive nature of TBSCC recurrences. Our findings seem to support the use of non-surgical treatments (chemotherapy, radiotherapy, or specialist palliative care) in patients with loco-regionally advanced recurrent TBSCC. Salvage surgery might be considered for early recurrences when radicality is still achievable. Precise guidelines for the rational follow-up of surgically-treated TBSCCs need to be shared between tertiary centers.

Factor V Leiden (FVL) is by far the most prevalent inherited thrombophilic abnormality in Western countries, and this genetic condition has been associated with sudden sensorineural hearing loss (SSHL). Audiologists should be aware that SSHL may be the precursor of life-threatening thromboembolic events, especially in Caucasians who are more likely to be FVL carriers.Case report.A 41-year-old male patient.Although this is not the first report of SSHL in a FVL carrier, it is the first to describe SSHL occurring in a heterozygous FVL carrier who--within a month--was also diagnosed with deep vein thrombosis of the left common femoral, saphenous, and popliteal veins, and pulmonary embolism of the left pulmonary artery branch serving the posterior basal segment of the inferior lobe.SSHL is an emergency condition that warrants prompt medical examination and treatment. Hematological investigations should be considered in SSHL patients at least for those with a family history of thrombotic events, and for women on estrogen-progestin therapy or during pregnancy, with a view to providing adequate antithrombotic prophylaxis and reducing the risk of other thromboembolic events.

Background Combining primary surgery with postoperative radiotherapy (RT) significantly reduces locoregional recurrence rates in selected patients with laryngeal squamous cell carcinoma (SCC). A prognostic model was used to see if associating laryngeal SCC tissue markers (mammary serine protease inhibitor [MASPIN], CD105, angiogenin [ANG], and nm23-H1) with conventional criteria could better discriminate higher-risk patients warranting postoperative RT. Methods The study involved 76 consecutively operated patients with laryngeal SCC not recommended for postoperative RT, in accord with current guidelines. Results On multivariate statistical modeling, non-nuclear MASPIN expression (p = .022), a CD105 expression ≥5.28% in vascular endothelial cells (p = .003), an nm23-H1 nuclear expression in carcinoma cells ≤12.0% (p = .028), and an ANG expression ≥5.0% (p = .07, statistical trend) showed a negative prognostic significance. The discriminatory power for disease recurrence of the 4 considered biomarkers generated an area under the curve (AUC; receiver operating characteristic [ROC]) of 0.872. The Hosmer–Lemeshow scale indicated an excellent discriminatory power. Conclusion This panel's ability to predict laryngeal SCC recurrence warrants further prospective, randomized studies to assess its use among the parameters routinely considered before recommending postoperative RT for patients with laryngeal SCC. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1534–1540, 2014

Nuclear nm23-H1 expression may be useful in identifying elderly patients operated for laryngeal squamous cell carcinoma (LSCC) at higher risk of recurrence. Further studies are needed to clarify the biological role of nm23-H1 in elderly patients with LSCC and to determine how to restore nm23-H1 loss of expression/function.Nowadays more than 50% of cancer cases are elderly patients and this percentage is expected to be 70% by 2030. Despite advances in LSCC diagnosis and treatment, patient survival has not improved in the last two decades. Novel, effective strategies should rely also on receptor-mediated LSCC-targeted therapy. nm23-H1 protein is related to the tumor cells' metastatic potential, and low nm23-H1 expression in carcinomas often correlates with a poor prognosis.Immunohistochemistry and image analysis were used to investigate the prognostic value of nm23-H1 expression and subcellular localization in a series of 54 elderly patients consecutively undergoing primary surgery for LSCC.On univariate analysis, the disease recurrence rate correlated inversely with nuclear nm23-H1 expression (p = 0.014), and disease-free survival (DFS) was longer in patients whose nuclear nm23-H1 levels were ≥2.0% (p = 0.022). On multivariate analysis, nuclear nm23-H1 expression (hazard ratio (HR) 2.77, p = 0.022) and N stage (HR 3.49, p = 0.007) were prognostically significant in terms of DFS.

Our primary aim was to use nasal cytology to compare a group of woodworkers with a group of unexposed subjects to see whether wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary aim was to seek any differences in nasal symptoms or nasal cytology between workers exposed to softwood vs hardwood dust, thereby comparing the inflammatory harmful potential of the two woods. Among 117 woodworkers at factories in the Veneto region (Italy), 40 exposed to either softwood or hardwood dust were assessed by means of a questionnaire, nasal cytology, and personal wood dust sampling, and compared with 40 unexposed controls. Woodworkers reported significantly more nasal symptoms than controls (p = 0.0007). The woodworker group's nasal smears contained significantly more neutrophils (p

Marioni G, Ottaviano G, Lionello M, Lora L, Lovato A, Staffieri C, Favaretto N, Giacomelli L, Stellini E, Staffieri A & Blandamura S (2012) Histopathology Nm23-H1 nuclear expression is associated with a more favourable prognosis in laryngeal carcinoma: univariate and multivariate analysis Aims: To use image analysis and multivariate analysis to investigate the prognostic significance of Nm23-H1 subcellular localization in a large cohort of laryngeal squamous cell carcinomas (LSCCs). Methods and results: Nm23-H1 total and nuclear levels were immunohistochemically determined and calculated with an image analysis system in 104 consecutively operated LSCCs. The mean follow-up was 58.3 ± 35.1 months (median 45 months). Total Nm23-H1 levels correlated only with patient stratification by pT (P = 0.01). Mean nuclear Nm23-H1 levels were lower in patients with recurrent disease (P = 0.01), and disease-free survival (DFS) was longer in patients whose nuclear levels of Nm23-H1 were >2.0% than in those with levels ≤2.0% (P = 0.019). On multivariate analysis, Nm23-H1 nuclear expression [hazard ratio (HR) 2.59, P = 0.005] and N stage (HR 3.60, P = 0.0001) were prognostically significant in relation to DFS. Conclusions: In LSCC, Nm23-H1 nuclear expression may be useful for identifying patients at higher risk of recurrence after treatment and who might be considered for more aggressive therapy. Further investigations are needed before Nm23-H1 can be considered for use in targeted treatments for LSCC.

BackgroundLaryngeal verrucous squamous cell carcinoma (VSCC) is a highly differentiated squamous cell carcinoma (SCC), the diagnosis of which can meet with many pitfalls: benign hyperplastic lesions and conventional SCC are the most important differential diagnoses. The microRNA miR-19a is overexpressed in many solid tumours and regulates the suppressor of cytokine signalling-1 (SOCS-1) expression.AimsThe main endpoints were to assess miR-19a and SOCS-1 expression in glottic VSCC, and the former's potential role in differentiating between glottic VSCC, conventional SCC and hyperplastic lesions.MethodsThe expression of MiR-19a (by reverse transcription and quantitative real-time PCR) and SOCS-1 (by immunohistochemistry, rabbit polyclonal anti-SOCS-1 antibody) was assessed in 11 consecutive cases of glottic VSCC, 20 of papillary hyperplasia and 42 cases of conventional SCC.ResultsMean miR-19a expression was significantly higher (p=0.000) in malignant glottic lesions (conventional SCC/VSCC) than in benign conditions. Significant differences in mean miR-19a expression also emerged between conventional SCC and papillary hyperplasia (p=0.000), and between conventional SCC and VSCC (p=0.03). miR-19a expression was not statistically associated with SOCS-1 immunoreactivity or immunostaining intensity in VSCC, conventional SCC or papillary hyperplasia.ConclusionsOur preliminary outcomes suggest the utility of miR-19a in the challenging differential diagnosis of laryngeal VSCC. Although miR-19a has been found to regulate SOCS-1 expression, this evidence was not confirmed by this investigation.

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a distinctly poor prognosis in advanced cases. There is still much controversy surrounding the rational diagnostic/therapeutic approach to TBSCC. Diagnostic differences are due mainly to: the small number of cases reported (even in the largest available series); the inappropriate histological heterogeneity of several case series; the lack of an internationally-accepted staging system for TBSCC; the frequent absence of adequate radiological imaging to enable a malignancy's local, regional and distant extension to be studied in detail; and a non-standardized approach to final histological assessment of the surgical margins. As for the therapeutic approaches, several issues are still debated, including the choice between en bloc and piecemeal primary surgery for the tumor's removal, and the role of elective neck dissection. Although radiotherapy seems to be an effective adjuvant therapy in advanced cases, its role in low-stage tumors or as a primary treatment has yet to be established. The value of chemotherapy is also still unclear. The treatment strategy for TBSCC is often based on the combined experience of a given surgeon and institution, bearing the results reportedly achieved by other oncology centers in mind. To date, the optimal management of TBSCC is still elusive. We aimed to critically review the ongoing crucial issues concerning the management of TBSCC, analyzing how it is diagnosed, staged and treated, the management of recurrences, rational follow-up schedules, and prognostic factors for this disease.

Laryngeal squamous cell carcinoma (LSCC) recurrences are very difficult to manage in elderly patients (age ≥65 years), because treatment carries significant morbidity and mortality. The aim of this study was to develop a panel of parameters (clinicopathological variables or biomarkers) to improve our ability to detect elderly patients at higher risk of LSCC recurrence. Maspin, nm23-H1, and CD105 were investigated using immunohistochemistry on surgical specimens from 46 elderly patients treated for LSCC. After univariate analysis identified parameters associated with LSCC recurrence, a multivariate prognostic model was constructed. At univariate analysis, a higher recurrence rate was significantly associated with nm23-H1 nuclear expression in carcinoma cells ≤2.0 % (p = 0.01), CD105 expression in intratumoral vascular endothelial cells ≥5.28 % (p = 0.04), and pN+ status (p = 0.04). Multivariate modeling confirmed that nuclear nm23-H1 ≤2.0 % (p = 0.009) and CD105 ≥5.28 % (p = 0.013) had a negative prognostic significance in terms of disease recurrence, while pN+ status showed a trend toward significance (p = 0.05). We thus obtained a panel comprising two biomarkers and neck lymph node status that revealed an excellent discriminatory power [AUC (ROC) of 0.81] in terms of the risk of LSCC recurrence. The panel achieved a specificity of 96 % and a positive predictive value of 93 %. We identified a panel with an excellent discriminatory power in identifying elderly patients at higher risk of recurrence after treatment for LSCC. These patients would benefit from a more aggressive primary treatment.

The aim of the present study was to investigate if any of the three awake procedures [fiberoptic nasopharyngoscopy with modified Muller Maneuver (FNMM), nasal snoring endoscopy (NSE), or oral snoring endoscopy (OSE)] could efficiently predict the grade or pattern of upper airway (UA) collapse found with drug-induced sleep endoscopy (DISE), which is considered by many authors as the current gold standard in optimizing obstructive sleep apnea syndrome (OSAS) patient selection for UA surgery. Twenty consecutive patients (simple snorers and OSAS patients) were studied with FNMM, NSE, OSE, and DISE. The inter-test agreement was evaluated with Cohen’s kappa coefficient (κ). In the current series, we found that NSE and OSE were better than FNMM in predicting the pattern of collapse found with DISE. A significant pattern agreement between NSE and DISE was present in all sub-sites, and the agreement was measured with a scale proposed by Landis and Koch as: moderate in velo- and oropharynx (κ = 0.52, p = 0.001, and κ = 0.47, p = 0.003, respectively), and substantial in hypopharynx (κ = 0.63, p

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a significant local recurrence rate even in patients with postoperative pathology reports of free surgical margins. This raises the question of how “free” negative margins should be to be oncologically safe, especially in bone tissue. A potential role for relaxin-2 hormone in tumor-driven osteolysis has recently been reported. The aim of this study was to assess the prognostic role of relaxin-2 expression in TBSCC tissue specimens and pathologically negative bone margins. Relaxin-2 immunohistochemical expression was assessed in 25 consecutively operated TBSCC patients. Several pathological variables correlated with recurrence rate (pT stage, dura mater involvement), disease-free survival (DFS) (pT stage, pN status, grade, and dura mater involvement), and disease-specific survival (DSS) (pT stage, pN status, grade, and dura mater involvement). The recurrence rate, DFS, and DSS did not correlate with relaxin-2 expression in TBSCC specimens or pathologically negative bone margins. Although local recurrence in TBSCC could relate to neoplastic bone invasion not apparent on conventional pathological investigations, the present preliminary findings seem to rule out any role of relaxin-2 in mediating this local aggressiveness. Molecular mechanisms of TBSCC recurrence after curative treatment should be further investigated.

Combining primary surgery with postoperative radiotherapy (RT) significantly reduces locoregional recurrence rates in selected patients with laryngeal squamous cell carcinoma (SCC). A prognostic model was used to see if associating laryngeal SCC tissue markers (mammary serine protease inhibitor [MASPIN], CD105, angiogenin [ANG], and nm23-H1) with conventional criteria could better discriminate higher-risk patients warranting postoperative RT.The study involved 76 consecutively operated patients with laryngeal SCC not recommended for postoperative RT, in accord with current guidelines.On multivariate statistical modeling, non-nuclear MASPIN expression (p = .022), a CD105 expression ≥ 5.28% in vascular endothelial cells (p = .003), an nm23-H1 nuclear expression in carcinoma cells ≤ 12.0% (p = .028), and an ANG expression ≥ 5.0% (p = .07, statistical trend) showed a negative prognostic significance. The discriminatory power for disease recurrence of the 4 considered biomarkers generated an area under the curve (AUC; receiver operating characteristic [ROC]) of 0.872. The Hosmer-Lemeshow scale indicated an excellent discriminatory power.This panel's ability to predict laryngeal SCC recurrence warrants further prospective, randomized studies to assess its use among the parameters routinely considered before recommending postoperative RT for patients with laryngeal SCC.

Epidermal growth factor receptor (EGFR) is a trans-membrane tyrosine kinase taking part in cell transformation and tumor progression. One of the downstream pathways controlled by EGFR involves the mammalian target of rapamycin (mTOR), a proto-oncogene activated in several cell functions. Recent evidence seems to confirm that both EGFR and mTOR regulate angiogenesis. The aim of this study was to investigate the expression of EGFR and mTOR in laryngeal squamous cell carcinoma (LSCC) cells in a retrospective clinical setting and their correlation with tumor neo-angiogenesis, judged on the grounds of CD105-assessed microvascular density (MVD), and prognosis. We considered 76 consecutive patients with LSCC treated with surgery alone. Immunohistochemical expressions of EGFR, mTOR, and CD105 were measured using image analysis and findings underwent statistical analysis using univariate and multivariate models. We found that nodal status correlated significantly with patient prognosis in terms of disease-free survival (DFS) (p = 0.01). There was a strong direct correlation between mTOR and EGFR expression (p = 0.0003), and between mTOR and CD105-assessed MVD (p = 0.0025). Patients with a CD105-assessed MVD >5.28 % had a significantly higher recurrence rate (RR) (p = 0.026), and a significantly shorter DFS (p = 0.025). On multivariate analysis, only N stage [hazard ratio (HR) 3.54, p = 0.009] and CD105-assessed MVD (HR 2.87, p = 0.027) maintained their independent prognostic significance in terms of DFS. Judging from our promising findings, the EGFR-mTOR pathway should be investigated further to understand its role in LSCC neo-angiogenesis.

It is a well known fact that sulphuric acid production is a highly exothermic process. In that sense, combined with the increased energy cost, surprisingly little heat is recovered from the process. Most often the heat is just cooled off by means of seawater or in air coolers. When recovering heat from the absorption and drying tower coolers, only minor changes to the process are needed. With plate heat exchangers (PHEs), the heat in the sulphuric acid can be recovered with negligible temperature losses and minimum space requirements. The PHE can take crossing temperature programs temperature pinches of less than 5°C and still having k -values of about 2500 kW/(°C·m 2 ). The heat recovered can be used for district heating of cities, boiler feed water preheating or as heating media in connected processes or adjacent plants. A very interesting use of this heat is for the production of fresh water by desalination of sea or brackish water, when the sulphuric acid plants are situated close to the coast such as several installations in Middle East and Northern African countries. The thermal duties in the acid coolers are very well adapted for heat recovery in combination with production of fresh water by means of multi effect distillation (MED). Evaporation temperature in a MED system is typically lower than 80°C, and the heating energy required is in the range of 60–360 kWh per produced m 3 of fresh water, depending on the number of effects. There are many advantages, both installation-wise and operation-wise, using PHE for highly efficient sulphuric acid heat recovery and falling film plate evaporators for the thermal surface in the desalination system. The high k -value of the plate system gives smaller heat transfer areas and compact installations.

The diversity of rhizobia in agricultural soils planted with soybean (Glycine max L.) and managed under conventional or notillage practices was evaluated by using a combination of trap-host capture and DNA fingerprinting approaches. Fifty-eight rhizobia isolates were captured using pigeonpea (Cajanus cajan L.) as a trap-host and characterised by using the RAPD DNA fingerprinting technique, yielding 25 different RAPD profiles. The application of the Shannon‐Weaver diversity index demonstrated that the diversity of rhizobia was significantly reduced in soil samples from plots cultivated with soybean compared with original uncultivated pasture plots. # 1999 Elsevier Science B.V. All rights reserved.

Desalination systems employing the distillation process have long since depended on basic shell and tube heat transfer technology. This basic form of heat transfer has been acceptable in the past, but as the economics of systems becomes more important, and as waters for desalination become more diverse, then the total cost aspect of the project becomes essential. An alternative heat transfer technology is now becoming more dominant in the desalination market — plate heat exchangers. Plate-type desalination systems have been in operation since 1967, and some 70% of the world's ships and offshore installations are using plate technology due to the advantages inherent in the system design. The plate concept applied in the Alfa Laval Water Technologies multi-effect plate (MEP), multi-effect thermo-vapour compression (TVC) and vacuum vapour compression (VVC) has distinct advantages over earlier technologies and offers owners and operators significant total cost savings. The high heat transfer coefficient achievable in the plate concept leads to relatively low heat transfer areas. This, along with the inherent low hold-up volume, leads to an extremely compact design giving a small footprint and corresponding to low civil costs. For most applications Alfa Laval applies titanium plates inside a duplex stainless steel vessel. Niether the Alfa Laval plate nor tubular units are designed to operate with waters containing high calcium sulphate. All heat transfer surfaces suffer if subjected to high sulphates, but the significant difference between the plate and the tube is that the plate can be completely cleaned on both sides. In this manner the heat transfer area always remains totally effective, removing any need to incorporate redundancy in design.

Nella visione imperiale che emerge dalle novellae, il potere legislativo ha origini divine e l'imperatore stesso è « legge vivente », concessa da Dio agli uomini (Nov. 72 praef. ; 113,1 pr. ; 137 praef. ; 105,2,4). Com'è noto, l'ambizioso progetto giustinianeo di una monarchia universale si reggeva sulla forza delle armi e del diritto, e si esprimeva nel topos arma-leges presente in alcuni documenti ufficiali (p. es. in Const. Summa pr. e in Const. Imperatoriam pr.). Consapevole del ruolo supremo di conditor legum, già pochi mesi dopo l'ascesa al trono Giustiniano comunicava al mondo bizantino l'avvio della celebre impresa che, com'egli stesso affermava (Const. Haec pr.), i suoi predecessori non avevano osato eseguire. Il fine dichiarato era quello di amputare prolixitatem litium, e per realizzarlo si concedevano alla commissione incaricata della stesura del novus Codex ampi poteri d'intervento e modifica sulla normativa raccolta. In tal modo si 'attualizzava' il diritto per scopi pratici, mediante la manipolazione sistematica dei testi legislativi, ai quali si doveva far ricorso nella prassi della recitatio. Per sostenere le proprie ragioni, le parti di una controversia e i loro difensori potevano allegare nei tribunali anche le opinioni dei vecchi giuristi secondo i criteri stabiliti dalla legge delle citazioni del 426, che era stata accolta nel primo codice. Nel giro di pochi mesi si verifica però un radicale mutamento di prospettiva, in ordine alle modalità d'impiego degli scritti dei giuristi. Il mutamento è documentato dal nuovo programma tracciato nel dicembre del 530 dalla Const. Deo Auctore. Abbandonato il parametro del rinvio a fonti « esterne », utilizzabili secondo un rigido calcolo meccanico, si annuncia l'idea di un'antologia in cui sarà recepita una parte cospicua, ma selezionata, dell'antico pensiero giurisprudenziale. Verrà di conseguenza precluso il ricorso a testi non compresi nella grandiosa raccolta. È probabile che tale idea maturasse tra la primavera del 529, dopo la pubblicazione del primo Codice, e l'autunno del 530, e che avesse ispirato l'emanazione delle Quinquaginta Decisiones. L'opera che vede la luce sullo scorcio del 533 non è una semplice antologia antiquaria : è un testo normativo che segna una netta cesura con il passato sotto un profilo specifico, rappresentato dalla forma autoritativa di un codice ufficiale per l’impiego dell'antico ius controversum. Non solo. Il lavoro di selezione e di elaborazione svolto, la consummatio nostrorum digestorum, produce effetti rilevanti sulla gerarchia delle fonti applicabili nella prassi della recitatio. In the imperial vision that emerges from novellae, the legislative power has divine origins and the emperor himself is "living law", granted by God to men (Nov. 72 Praef.; 113.1 pr.; 137 praef.; 105,2,4). As is known, the ambitious Justinian project of a universal monarchy relies on the strength of the weapons and the law, and is expressed in topos arma-leges present in some official documents (e.g.. in Const. Summa pr. and in Const. Imperatoriam pr.). Being aware of the supreme role of conditor legum, already a few months after his ascent to the throne Justinian informed the Byzantine world of the start of the famous enterprise that, as he himself stated (Const. Haec pr.), his predecessors had not dared to accomplish. The stated goal was to amputare prolixitatem litium, and to achieve that, the committee responsible for the drafting of the Novus Codex were given wide powers of intervention and modification of the collected rules. This way, the right was being "actualized" for practical purposes, by the systematic manipulation of the legislative texts used in the practice of recitatio. In order to support their own reasons, the parties to a dispute and their defenders could produce in court also the views of the old lawyers according to the criteria established by the 426 law of the quotes, which had been accepted in the first code. In a few months, however, a radical change of perspective concerning the use of the jurists writings takes place. The change is documented by the new program outlined in December 530 by Const. Deo Auctore. Once the parameter of the referral to 'external' sources, to be used according to a rigid mechanical calculation, has been abandoned, it is proposed the idea of an anthology in which a large, but selected, portion of the ancient jurisprudential thought will be transposed. The usage of texts not included in the grand collection will therefore be precluded. It is likely that this idea took form between the spring of 529, after the publication of the first Code, and the autumn of 530, and that it inspired the enactment of Quinquaginta Decision. The work that sees the light on the early 533 is not a simple antiquarian anthology, but rather a regulatory text that marks a sharp break with the past under a specific profile, represented by the authoritative form of an official code for the usage of the ancient ius controversum. Moreover, the selection and processing work that has been done, the consummatio nostrorum digestorum, produces significant effects on the hierarchy of sources applicable in the practice of recitatio.

Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at high risk of recurrence after surgery. There are currently no clinicopathological parameters available to predict response to such adjuvant RT in LSCC, and only a few potentially predictive biomarkers have been investigated. Nm23-H1 protein is reportedly related to the tumor cells’ metastatic potential, and low Nm23-H1 expression levels in human carcinomas often correlate with a poor prognosis. The novel aim of the present preliminary study was to investigate the prognostic value of Nm23-H1 expression and subcellular localization in a series of patients given postoperative RT for LSCC. A retrospective clinicopathological investigation was conducted at an academic tertiary referral center of 28 consecutive patients given postoperative RT for LSCC. Image analysis of immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear expression levels. Disease-free survival (DFS) was significantly shorter among LSCC patients with total Nm23-H1 levels

Summary Objectives The aim of this study was to compare the discriminatory power of the Multi-Dimensional Voice Program ( MDVP ) and Praat in distinguishing the gender of euphonic adults. Study Design This is a cross-sectional study. Methods The recordings of 100 euphonic volunteers (50 males and 50 females) producing a sustained vowel /a/ were analyzed with MDVP and Praat software. Results Both computer programs identified significant differences between male and female volunteers in absolute jitter ( MDVP P Praat P MDVP P = 0.006 and Praa t P = 0.001). Using the scale proposed by Hosmer and Lemeshow, we found no gender discrimination for shimmer in dB with either the MDVP (area under the receiver operating characteristics curve [AUC] = 0.658) or Praat (AUC = 0.682). In our series, on the other hand, MDVP absolute jitter achieved an acceptable discrimination between males and females (AUC = 0.752), and Praat absolute jitter achieved an outstanding discrimination (AUC = 0.901). The discriminatory power of Praat absolute jitter was significantly higher than that of the MDVP ( P = 0.003). Absolute jitter sensitivity and specificity were also higher for Praat (83% and 80%) than for the MDVP (74% and 49%). Conclusions Differences attributable to a subject's gender and to the software used to measure acoustic parameters should be carefully considered in both research and clinical settings. Further studies are needed to test the discriminatory power of different voice analysis programs when differentiating between normal and dysphonic voices.

Dynamic covalent chemistry forms the key ingredient for a new approach toward organic synthesis. Dynamic covalent chemistry regards the synthesis of covalent organic molecules under thermodynamic control. It relies on the use of covalent bonds that can be reversibly formed under the experimental conditions. It combines the advantages typically associated with noncovalent synthesis (the formation of molecular structures using noncovalent interactions), such as spontaneous formation, error correction, and proof reading, with the robustness of covalent bonds. For many covalent bonds, experimental conditions under which the reaction occurs reversibly are known, but the majority of systems relies on trans(thio)esterifications and disulfide or imine-type exchange reactions. These reactions occur rapidly under mild conditions, use readily accessible building blocks, and can be turned off to obtain kinetically inert products. It is illustrated that dynamic covalent chemistry gives a rapid access toward organic structures of nanometer dimensions. Typically, a one-step, one-pot synthetic protocol is used, which in some cases also involves multiple dynamic covalent bonds in an orthogonal manner. The fundamental difference with covalent synthesis is that equilibrium reactions are used. This introduces a characteristic property, which is the possibility of the chemical system to adapt to changes in its environment according to Le Châtelier's principle. This concept is referred to as dynamic combinatorial chemistry (DCC) and has been successfully applied for the preparation of new receptors, guests, sensors, materials, and so forth. Examples, together with the potential and limitations of this approach, are discussed. The final section is dedicated to the systems in which dynamic covalent bonds provide structural stability but intramolecular noncovalent interactions determine the composition of the resulting equilibrium. It is shown that this approach, that is, dynamic covalent capture, is a very sensitive tool for the quantification of weak interactions, for instance, in protein folding or catalysis. Keywords: dynamic covalent bonds; thermodynamic control; dynamic combinatorial chemistry; receptors; catalysis; materials; dynamic covalent capture; organic nanostructures

Dynamic covalent chemistry forms the key ingredient for a new approach toward organic synthesis. Dynamic covalent chemistry regards the synthesis of covalent organic molecules under thermodynamic control. It relies on the use of covalent bonds that can be reversibly formed under the experimental conditions. It combines the advantages typically associated with noncovalent synthesis (the formation of molecular structures using noncovalent interactions), such as spontaneous formation, error correction, and proof reading, with the robustness of covalent bonds. For many covalent bonds, experimental conditions under which the reaction occurs reversibly are known, but the majority of systems relies on trans(thio)esterifications and disulfide or imine-type exchange reactions. These reactions occur rapidly under mild conditions, use readily accessible building blocks, and can be turned off to obtain kinetically inert products. It is illustrated that dynamic covalent chemistry gives a rapid access toward organic structures of nanometer dimensions. Typically, a one-step, one-pot synthetic protocol is used, which in some cases also involves multiple dynamic covalent bonds in an orthogonal manner. The fundamental difference with covalent synthesis is that equilibrium reactions are used. This introduces a characteristic property, which is the possibility of the chemical system to adapt to changes in its environment according to Le Châtelier's principle. This concept is referred to as dynamic combinatorial chemistry (DCC) and has been successfully applied for the preparation of new receptors, guests, sensors, materials, and so forth. Examples, together with the potential and limitations of this approach, are discussed. The final section is dedicated to the systems in which dynamic covalent bonds provide structural stability but intramolecular noncovalent interactions determine the composition of the resulting equilibrium. It is shown that this approach, that is, dynamic covalent capture, is a very sensitive tool for the quantification of weak interactions, for instance, in protein folding or catalysis. Keywords: dynamic covalent bonds; thermodynamic control; dynamic combinatorial chemistry; receptors; catalysis; materials; dynamic covalent capture; organic nanostructures

Patients with head and neck squamous cell carcinoma (SCC) respond very differently to radiotherapy (RT). Since clinical factors cannot accurately predict its effects, biological parameters have been investigated, including tumor hypoxia. CD105 is a hypoxia-inducible glycoprotein emerging as a potential prognostic indicator for several solid malignancies. Angiogenin is upregulated under hypoxic conditions and supports primary and metastatic tumor growth. Epidermal growth factor receptor (EGFR) activation stimulates tumor proliferation and angiogenesis. The aim of the present study was to ascertain the prognostic importance of hypoxia-inducible factors (CD105, angiogenin) and EGFR in a series of patients who underwent primary surgery followed by RT for laryngeal SCC. 25 consecutive patients with laryngeal SCC given postoperative RT have been investigated. CD105, angiogenin, and EGFR immunohistochemical expressions in primary laryngeal SCCs have been evaluated also with image analysis. The recurrence rate was significantly higher in SCC patients with a CD105 expression >10.0% (P = 0.012) and their disease-free survival (DFS) was shorter (P = 0.044). Neither angiogenin (in the carcinoma cells or endothelial cells) nor EGFR expression were associated with the prognosis in our patients after primary surgery followed by RT for laryngeal SCC. CD105 should be studied as a potentially predictive biomarker for identifying laryngeal SCCs at higher risk of early recurrence after postoperative RT. Targeted anti-CD105 therapy associated with RT should also be investigated in patients with laryngeal SCCs characterized by high CD105 expression.

European Annals of Otorhinolaryngology, Head and Neck Diseases - Vol. 132 - N° 3 - p. 175

OBJECTIVES: In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC). METHODS: Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes. RESULTS: On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P

Purpose Despite recent advances in diagnostic and therapeutic techniques, the prognosis for patients with head and neck squamous cell carcinoma (HNSCC) has not improved significantly. Novel clinical strategies are needed to identify HNSCC patients with a poor prognosis, who may benefit from a tailored therapy. Several bio-markers have been recently considered for prognostic purposes in oral carcinoma. Angiogenin (ANG) is a member of the ribonuclease superfamily and of medical interest largely because it supports the growth of primary and metastatic malignancies. ANG has recently been found involved in cancer cell proliferation as well as in tumor angiogenesis. The present study is the first to investigate the potential role of ANG in tongue carcinoma neo-angiogenesis and cancer cell proliferation. Materials and methods ANG expression (in carcinoma cells and endothelial intratumor vessel cells), CD105-assessed micro-vessel density (MVD), and MIB-1 expression were correlated with prognostic parameters in 28 consecutively-operated pT1–T2 tongue carcinomas (SCC). Whenever feasible, a computer-based image analysis system was used for the immunohistochemical reaction analysis. Results No significant correlations emerged between ANG expression in the tongue carcinoma cells or endothelial intratumor vessel cells and tongue carcinoma recurrence or disease-free survival (DFS). ANG expression was also unrelated to CD105-assessed MVD or MIB-1 expression. Conversely, CD105-assessed MVD correlated directly with recurrence rate (p = 0.02), and DFS was significantly shorter in cases with CD105-assessed MVD > 167 micro-vessels/mm2 than in those with MVD ⩽ 167 micro-vessels/mm2(p = 0.042). Conclusions Our results support the hypothesis that CD105-assessed MVD would be a valuable parameter for predicting which patients with tongue SCC are at greatest risk of carcinoma recurrence. Despite our study results, the role of ANG in tongue carcinoma warrants further investigation in larger series because blocking ANG expression might have the potential not only to reduce angiogenesis in malignancies, but also to directly inhibit tumor growth.

The chapter is based on a survey of para-legal terminology in the Major Declamations. The terms here defined as ‘para-legal’ are (1) expressions used in declamatory texts as technical terms, but having a different meaning in Roman legal literature; (2) terms that originate from legal language but in declamations lose their original sense and acquire instead a metaphorical or generic connotation. The latter type, much less studied than the former, reveals the close proximity of declamation to legal literature, which deeply influences the imagery of the declaimers as well as their language. Moreover, the distribution of such para-legal terms throughout the pseudo-Quintilianic corpus clearly brings out the differences between the Major and Minor Declamations as far as style and aims are concerned.

[Quintilian]’s declamations are imaginary trials, but technical details concerning those trials mostly remain in the background. In order to shed light on such aspects, this paper follows a number of different research paths (including a special focus on torture in Decl. mai. 7) and finally draws some innovative conclusions as to the representation of the parties and the trial dynamics that emerge from Latin rhetorical texts in general, and the Major Declamations in particular. This is an especially helpful approach in order to gain a better understanding of the legal practice under the Principate, and, above all, of the training of advocates in imperial Rome.