Role of triglyceride-glucose index in metabolic assessment of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ. It leads to an increased risk of metabolic syndrome and insulin resistance, due to biochemical pathways involved in low-grade inflammation in both diseases. The aim of our retrospective case-control study was to evaluate the utility of triglyceride-glucose (TyG) index, a surrogate of insulin resistance, for metabolic assessment of sarcoidosis patients. A cohort of 90 sarcoidosis patients and a cohort of 90 control subjects were enrolled. Clinical, anamnestic, and biochemical data were collected. Results showed that TyG index values were higher in the sarcoidosis cohort than in the control group (p < 0.001), even after excluding the influence of diabetes and metabolic syndrome (p = 0.018). In the sarcoidosis cohort, TyG index was not correlated with clinical phenotyping (p = 0.358), gender (p = 0.139), radiological stage (p = 0.656), glucocorticoids cumulative dose (p = 0.682) or treatment regimen (p = 0.093), while significant positive correlations with waist circumference (p < 0.001), systolic and diastolic pressure (p = 0.041 and p = 0.029, respectively), Framingham score (p = 0.007) were found. Receiving operating characteristics curve analysis identified a TyG index optimal cut-off value of 8.64 (66.7% sensitivity, 77.8% specificity, area under the curve -AUC- 75%, 95% confidence interval -CI- 65-85, p < 0.001) to detect metabolic syndrome and a cut-off value of 8.69 (64.1% sensitivity, 70.6% specificity; AUC 67%, 95% CI 55-78, p = 0.007) to detect an intermediate cardiovascular risk according to Framingham risk score. Concluding, TyG index can be considered a useful tool for the metabolic assessment of sarcoidosis patients, given its capacity to predict metabolic syndrome and cardiovascular risk.

Minimal Compositionality versus Bird Implicatures: two theories of ABC-D sequences in Japanese tits.

It was argued in a series of experimental studies that Japanese tits (Parus minor) have an ABC call that has an alert function, a D call that has a recruitment function, and an ABC-D call that is compositionally derived from ABC and D, and has a mobbing function. A key conclusion was that ABC-D differs from the combination of separate utterances of ABC and of D (e.g. as played by distinct but close loudspeakers). While the logic of the argument is arguably sound, no explicit rule has been proposed to derive the meaning of ABC-D from that of its parts. We compare two analyses. One posits a limited instance of semantic compositionality ('Minimal Compositionality'); the other does without compositionality, but uses instead a more sophisticated pragmatics ('Bird Implicatures'). Minimal Compositionality takes the composition of ABC and D to deviate only minimally from what would be found with two independent utterances: ABC means that 'there is something that licenses an alert', D means that 'there is something that licenses recruitment', and ABC-D means that 'there is something that licenses both an alert and recruitment'. By contrast, ABC and D as independent utterances yield something weaker, namely: 'there is something that licenses an alert, and there is something that licenses recruitment', without any 'binding' across the two utterances. The second theory, Bird Implicatures, only requires that ABC-D should be more informative than ABC, and/or than D. It builds on the idea, proposed for several monkey species, that a less-informative call competes with a more informative one (the 'Informativity Principle'): when produced alone, ABC and D trigger an inference that ABC-D is false. We explain how both Minimal Compositionality and Bird Implicatures could have evolved, and we compare the predictions of the two theories. Finally, we extend the discussion to some chimpanzee and meerkat sequences that might raise related theoretical problems.

Cardiovascular risk in rare diseases: a prognostic stratification model in a cohort of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ; as other chronic diseases, it leads to increased risk of atherosclerosis and cardiovascular (CV) disease. The aim of our observational study was to define a prognostic stratification model of sarcoidosis patients based on the evaluation of CV risk through common carotid Doppler ultrasound and cardiovascular risk scores assessment; for this reason, a clinical phenotyping of sarcoidosis patients in four subgroups was done, based on the different organ involvement. A cohort of 53 sarcoidosis patients and a cohort of 48 healthy volunteers were enrolled. Results showed that CV risk was higher in sarcoidosis cohort than in the control group when evaluated through CV risk scores and Doppler parameters: peak-systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly lower in sarcoidosis cohort (p = 0.045 and p = 0.017, respectively), whereas intima media thickness (IMT) showed higher values in sarcoidosis group than in controls (p = 0.016). The analysis of sarcoidosis phenotypes showed no significative differences of CV risk among them when CV risk scores were considered, while partial differences emerged by evaluating subclinical atherosclerosis. Results also highlighted a relationship between CV risk score and carotid Doppler ultrasound parameters: EDV showed an inverse correlation with Framingham score (R = - 0.275, p = 0.004), whereas IMT showed a direct one (R = 0.429; p = 0.001); furthermore, an inverse correlation between PSV and EDV and illness duration (R = - 0.298, p = 0.030 and R = - 0.406, p = 0.002, respectively) was found, so suggesting a higher CV risk in patients with a longer story of disease.

Sarcoidosis and autoimmunity: In the depth of a complex relationship.

Sarcoidosis is a chronic granulomatous disease that can virtually affect any organ. Its etiology is unknown, although it has been proposed that environmental or biological agents can act as triggers, ultimately leading to chronic inflammation in genetically predisposed individuals. The main component of sarcoid inflammation is represented by an exaggerated T- lymphocytic cellular response to a putative antigen that could not be efficiently cleared in the patient. However, several clinical and immunological observations, such as the association of sarcoidosis to autoimmune diseases or the presence of autoantibodies in the serum of patients with sarcoidosis, suggest that humoral-mediated immune response might also play a role in the pathogenesis of sarcoidosis. The aim of this review is to deepen the relationship between sarcoidosis and autoimmunity, by analyzing the most recent advances and proposing new fields of research.

Do infants have abstract grammatical knowledge of word order at 17 months? Evidence from Mandarin Chinese.

We test the comprehension of transitive sentences in very young learners of Mandarin Chinese using a combination of the weird word order paradigm with the use of pseudo-verbs and the preferential looking paradigm, replicating the experiment of Franck et al. (2013) on French. Seventeen typically-developing Mandarin infants (mean age: 17.4 months) participated and the same experiment was conducted with eighteen adults. The results show that hearing well-formed NP-V-NP sentences triggered infants to fixate more on a transitive scene than on a reflexive scene. In contrast, when they heard deviant NP-NP-V sequences, no such preference pattern was found, a performance pattern that is adult-like. This is at variance with some of the results from Candan et al. (2012), who only found evidence for canonical word order comprehension at almost age 3 when considering fixation time. Furthermore, within the age range tested, performance showed no effect of age or vocabulary size.

Clinical phenotyping in sarcoidosis management.

Sarcoidosis is a heterogeneous granulomatous disease. Biological markers and clinical features could allow specific phenotypes to be associated with different prognosis, severity and treatment responses. This retrospective multicentre study aims to analyse the clinical and immunological features of sarcoidosis and to identify a routine non-invasive biomarker useful in clinical practice. MATERIALS AND METHODS: 129 Caucasian patients with sarcoidosis (median age IQR, 56 (47-62)) were enrolled retrospectively in the study. Medical history, routine laboratory findings, lung function results and radiological features from the last examination of October 2019 - February 2020 were gathered from the patients' clinical records. RESULTS: Regardless their clinical status at disease onset, at the last clinical examination we didn't observe any differences in terms of therapeutic management between symptomatic and asymptomatic patients. Stratifying sarcoidosis population according to therapeutic management, the N/L ratio was higher in the treated group than in the non-treated group (p=0.0034). Receiver operating curve (ROC) analysis distinguished these two groups according to N/L ratio with an area under the curve (AUC) of 65.3% and a best cut-off value of 2.21. Peripheral N/L ratio was significantly higher in radiological stages 2-4 than in stages 0-1 (p=0.0090) distinguishing these two groups with an AUC of 64% and a best cut-off value of 2.13. DISCUSSION: In our multicentric cohort study similar periodic follow-up can be suggested for symptomatic and asymptomatic sarcoidosis patients at onset. In the heterogeneous context of this disease, N/L ratio proved to be a useful and simple routine laboratory biomarker related to disease activity and need for treatment.

The Layered Syntactic Structure of the Complementizer System: Functional Heads and Multiple Movements in the Early Left-Periphery. A Corpus Study on Italian.

In this paper we document the developmental trajectory of the complementizer system (CP-system) in Italian by looking at the earliest spontaneous production of eleven young children, whose transcriptions are available on CHILDES. We conducted a novel corpus analysis, tracking down a number of constructions in which the clausal left-periphery is activated. First, we considered the appearance of the different complementizer particles in the CP-system, which overtly realize the three distinct functional projections ForceP, IntP, and FinP. The analysis revealed that children acquiring Italian correctly use these complementizer particles already in the third year of life. Second, we looked for the simultaneous activation of different functional projections within the CP-system. We went through our corpus searching for complex sentences in which more than one constituent was moved to the left periphery. This option is allowed by the adult grammar of Italian and, as our search revealed, it is also attested in the grammar of young children. Soon after their second birthday, sequences in which a left-dislocated Topic and a Wh- element co-occur are attested, directly supporting the existence of a (high) Topic position above FocusP. Moreover, movement in general conforms to the constraints of the adult grammar, with no attested violation of obligatory inversion (a consequence of the Q-Criterion). Importantly, "why-questions" did not require inversion, much as in the adult grammar of Italian. Taken together, children's use of complementizer particles and their activation of multiple landing sites for movement show that 2-year-olds already possess a richly articulated functional structure of the CP-system, aligned to the layered adult structure. In concluding the paper, we also discuss some temporal differences between constructions activating high and low portions of the CP-system. In particular, we detect a temporal precedence for wh-questions over why-questions. Since the former activate a lower projection, this is consistent with the recently proposed Growing Trees hypothesis, according to which the development of the CP-system proceeds stepwise.

Treatment of Pyonephritis Complicated by Septic Shock Using Extracorporeal Device Polymyxin B-Hemoperfusion.

Direct hemoperfusion using polymyxin B-immobilized fiber (PMX-DHP) is an established treatment method for septic shock caused by Gram-negative infections. We report one instance in which PMX-DHP therapy has been used successfully in a 33-year-old woman with septic shock from urosepsis. Although there is lack of recommendations in latest Surviving Sepsis Campaign Guidelines, evidence of PMX-DHP efficacy in this subset of patients is growing.

Correction to: Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis.

After publication of our article [1] the authors have notified us that one of the names has been incorrectly tagged.

Morphosyntactic weaknesses in Developmental Language Disorder: the role of structure and agreement configurations.

Agreement is a morphosyntactic dependency which is sensitive to the hierarchical structure of the clause and is constrained by the structural distance that separates the elements involved in this relation. In this paper we present two experiments, providing new evidence that Italian-speaking children with Developmental Language Disorder (DLD), as well as Typically Developing (TD) children, are sensitive to the same hierarchical and locality factors that characterise agreement in adult grammars. This sensitivity holds even though DLD children show accrued difficulties in more complex agreement configurations. In the first experiment, a forced-choice task was used to establish whether children are more affected in the computation of S-V agreement when an element intervenes hierarchically or linearly in the agreement relation: DLD children are more subject to attraction errors when the attractor intervenes hierarchically, indicating that DLD children discriminate between hierarchical and linear configurations. The second experiment, also conducted through a forced-choice task, shows that the computation of agreement in DLD children is more 'fragile' than in TD children (and also in children with a primary impairment in the phonological domain), in that it is more sensitive to the factors of complexity identified in Moscati and Rizzi's (2014) typology of agreement configurations. To capture the agreement pattern found in DLD children, we put forth a novel hypothesis: the Fragile Computation of Agreement Hypothesis. Its main tenet is that DLD children make use of the same grammatical operations employed by their peers, as demonstrated in Experiment 1, but difficulties increase as a function of the complexity of the agreement configuration.

Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis.

BACKGROUND: Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients. METHODS: Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.8 ± 12.8 years). Clinical and respiratory functional characteristics, Clinical Outcome Scale (COS) classification, clinical phenotypes proposed by the GenPhenResA project, and radiological assessment, including CT scan, were collected. Serum sampling and clinical and functional assessments at follow-up were also included. RESULTS: Significantly higher chitotriosidase activity was observed in sarcoidosis patients than in healthy controls (p < 0.0001). Evidence of lung fibrosis with reticular abnormalities and traction bronchiectasis at High resolution CT, presence of multiple extrapulmonary sarcoid localizations and increased 24-h urinary excretion of calcium were associated with significantly higher chitotriosidase activity (p < 0.005). Patients with remitted or minimal disease had lower values of chitotriosidase than patients with persistent disease. At follow-up, patients who required an increase in steroid dose showed an increase in its activity. CONCLUSIONS: Chitotriosidase is a reliable biomarker of sarcoidosis. It is increased in patients with sarcoidosis correlating with disease activity, severity and multiorgan dissemination. Steroid therapy tended to reduce chitotriosidase expression, however it responded in cases of disease relapse.

Corrigendum: Task-dependency and structure-dependency in number interference effects in sentence comprehension.

[This corrects the article on p. 349 in vol. 6, PMID: 25914652.].

Task-dependency and structure-dependency in number interference effects in sentence comprehension.

We report three experiments on French that explore number mismatch effects in intervention configurations in the comprehension of object A'-dependencies, relative clauses and questions. The study capitalizes on the finding of object attraction in sentence production, in which speakers sometimes erroneously produce a verb that agrees in number with a plural object in object relative clauses. Evidence points to the role of three critical constructs from formal syntax: intervention, intermediate traces and c-command (Franck et al., 2010). Experiment 1, using a self-paced reading procedure on these grammatical structures with an agreement error on the verb, shows an enhancing effect of number mismatch in intervention configurations, with faster reading times with plural (mismatching) objects. Experiment 2, using an on-line grammaticality judgment task on the ungrammatical versions of these structures, shows an interference effect in the form of attraction, with slower response times with plural objects. Experiment 3 with a similar grammaticality judgment task shows stronger attraction from c-commanding than from preceding interveners. Overall, the data suggest that syntactic computations in performance refer to the same syntactic representations in production and comprehension, but that different tasks tap into different processes involved in parsing: whereas performance in self-paced reading reflects the intervention of the subject in the process of building an object A'-dependency, performance in grammaticality judgment reflects intervention of the object on the computation of the subject-verb agreement dependency. The latter shows the hallmarks of structure-dependent attraction effects in sentence production, in particular, a sensitivity to specific characteristics of hierarchical representations.

Open pelvic fracture associated with lumbosacral dislocation and extensive perineal injury.

Open pelvic fractures are caused by high-energy trauma. Injuries to other organs are common and the mortality rate can be as high as 50%. Perineal injury is reported in 5% of open pelvic fractures. We report a case of a 31-year-old man that had an open pelvic injury with Denis zone III fracture of the sacrum, lumbosacral dislocation, symphysis dislocation, bilateral pubic rami fractures and an extensile perineal wound. He underwent an early diverting colostomy in order to prevent pelvic sepsis and subsequent stage reconstruction of the pelvic ring. At a 4-year follow-up a full recovery was present. The aim of this paper is to underline the importance of a safe, approach to manage open pelvic fractures.

Short stems in total hip replacement: current status and future.

Short stem hip implants have been introduced as a bone preserving surgery for younger and more active people undergoing hip arthroplasty. Although many short stems are now available, clinical results and long-term survival are controversial. The aim of this paper is to describe the features of the short stems and to analyse their clinical results and long-term survival. The short-stem implants reproduce a stress distribution at the level of the proximal femur more similar to the physiological femur limiting the stress-shielding that occur with conventional cementless stems. Though short stems are an alternative to conventional stems, their use is not yet justified despite the promising short and mid-term survival results. Higher incidence of complications, such as periprosthetic fractures and malpositioning of the stem, and the lack of long-term results do not allow to predict what role in the future short stems in total hip replacement may have.

Management of hemodynamically unstable pelvic trauma: results of the first Italian consensus conference (cooperative guidelines of the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology -Section of Vascular and Interventional Radiology- and the World Society of Emergency Surgery).

Hemodynamically Unstable Pelvic Trauma is a major problem in blunt traumatic injury. No cosensus has been reached in literature on the optimal treatment of this condition. We present the results of the First Italian Consensus Conference on Pelvic Trauma which took place in Bergamo on April 13 2013. An extensive review of the literature has been undertaken by the Organizing Committee (OC) and forwarded to the Scientific Committee (SC) and the Panel (JP). Members of them were appointed by surgery, critical care, radiology, emergency medicine and orthopedics Italian and International societies: the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology, Section of Vascular and Interventional Radiology and the World Society of Emergency Surgery. From November 2012 to January 2013 the SC undertook the critical revision and prepared the presentation to the audience and the Panel on the day of the Conference. Then 3 recommendations were presented according to the 3 submitted questions. The Panel voted the recommendations after discussion and amendments with the audience. Later on a email debate took place until December 2013 to reach a unanimous consent. We present results on the 3 following questions: which hemodynamically unstable patient needs an extraperitoneal pelvic packing? Which hemodynamically unstable patient needs an external fixation? Which hemodynamically unstable patient needs emergent angiography? No longer angiography is considered the first therapeutic maneuver in such a patient. Preperitoneal pelvic packing and external fixation, preceded by pelvic binder have a pivotal role in the management of these patients.Hemodynamically Unstable Pelvic Trauma is a frequent death cause among people who sustain blunt trauma. We present the results of the First Italian Consensus Conference.

A person is not a number: discourse involvement in subject-verb agreement computation.

Agreement is a very important mechanism for language processing. Mainstream psycholinguistic research on subject-verb agreement processing has emphasized the purely formal and encapsulated nature of this phenomenon, positing an equivalent access to person and number features. However, person and number are intrinsically different, because person conveys extra-syntactic information concerning the participants in the speech act. To test the person-number dissociation hypothesis we investigated the neural correlates of subject-verb agreement in Spanish, using person and number violations. While number agreement violations produced a left-anterior negativity followed by a P600 with a posterior distribution, the negativity elicited by person anomalies had a centro-posterior maximum and was followed by a P600 effect that was frontally distributed in the early phase and posteriorly distributed in the late phase. These data reveal that the parser is differentially sensitive to the two features and that it deals with the two anomalies by adopting different strategies, due to the different levels of analysis affected by the person and number violations.

When persons disagree: an ERP study of Unagreement in Spanish.

Agreement is one of the main devices used by languages to signal grammatical relations. In this study, we investigated the neurophysiological processing correlates of subject-verb agreement in Spanish using Unagreement, a phenomenon characterized by a person mismatch between subject and verb that nonetheless produces a grammatical pattern. Unagreement was compared to well-formed sentences with full agreement, and ill-formed sentences with a person mismatch. Compared to control sentences, Unagreement produced a left posterior negativity followed by a more central negativity; no P600 effect was observed. In contrast, person violations generated a negativity that was widely distributed over the scalp, followed by a P600 effect. These data suggest that the comprehension of qualitatively different agreement patterns, which could reflect the performance of different processing routines, recruits different neural generators.