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Riassunto. Obiettivo. Lo scopo di questo studio trasversale è determinare la prevalenza dell'ipotiroidismo tra i pazienti in emodialisi (ED) e i suoi potenziali fattori di rischio. Metodi. Sono stati raccolti dati demografici e di laboratorio [vale a dire, livelli sierici di tireotropina (TSH), anticorpi anti-perossidasi tiroidea (anti-TPO)] di 117 pazienti con MH. I dati sono stati analizzati da SPSS.V 26, quando necessario. Risultati. I pazienti avevano un'età media (DS) di 59,47±15,08 anni e il 66,7% (n=78) era di genere maschile. I livelli medi (DS) di TSH erano 2,56 (4,01) μIU/mL. L'ipotiroidismo subclinico (SCH) è stato definito come un livello di TSH >4,2 μIU/mL e FT4 normale. Quindici pazienti (12,80%) avevano SCH. Non c'era correlazione significativa tra ipotiroidismo ed età, genere e/o malattie sottostanti (p>0,05). Inoltre, tra i 15 pazienti con SCH, 1 paziente (6,7%) ha mostrato un risultato anti-TPO positivo mentre 14 pazienti (93,3%) hanno avuto un risultato anti-TPO negativo. Conclusione. Data la notevole prevalenza dell'ipotiroidismo nei pazienti con ED, lo screening di routine della funzione tiroidea in questa popolazione di pazienti può aiutare a ridurre i tassi di complicanze e mortalità attraverso una diagnosi precoce e un intervento tempestivo.We believe that a high percentage of covid-19 infections could be due to the presence of false negative (FN) individuals on rapid swabs. To support this hypothesis and quantify their number, we performed simulations using Bayes' rule and various assumptions about the sensitivity, specificity of swabs and prevalence of infection. Imagining FNs in liberty, we then calculated the probability of encountering them in groups of people with a typical number of habitual sites, such as bus, supermarket, theatre, etc. The probability of encountering FN from rapid tests was more than 3 times higher (345% change) that reported by the RT-PCR test.In healthcare, uncertainty, far from being an exceptional event, is always present. The concept has been defined as the inability to decide, caused by a subjective perception of ignorance, a meta-ignorance. Ignorance may be seen as unacceptable in the context of healthcare, which seems to require certainties, hard evidence that allow exact predictions, and consequent professional decisions. For this reason, the professional who has to make decisions can be led to assume attitudes of aversion or denial of uncertainty, and to seek refuge in false certainties. In this article, we review the theoretical debate of the past decades and the current evidence around the management of uncertainty in clinical practice, especially in the primary care consultation. We argue that clinical situations can be represented as constituted by a core of risk, whit a known probability of the occurrence of an outcome. This known risk core is surrounded by a cloud of uncertainty, the wider the more the clinical information is vague aaccount improves the clinical reasoning. The higher the uncertainty, the higher the need of patients' involvement in the decision. Finally, we conclude the article by showing how the communication of uncertainty to patients favors the construction and maintenance of a good doctor-patient relationship, based on responsibility, trust and respect.The European regulation 536/2014, unapplied for several years due to the inoperability of the European Portal, represented an epochal turning point in the legislation concerning pharmacological clinical trials. Although, unlike the directive, it could be directly applied without national transpositions, in Italy this has not been possible and for three months now we have been witnessing a haemorrhage of guidelines/operational proposals/decrees that to date do not make us ready to fully operate according to the new rules. Il regolamento europeo 536/20141, in vigore dal 16 giugno 2014 e rimasto per diversi anni non applicato per un ritardo nella messa in funzione del portale unico europeo, ha rappresentato una svolta epocale nella normativa inerente le sperimentazioni cliniche con farmaco. La normativa precedentemente in vigore2, infatti, pur rappresentando la prima trasformazione in legge delle Good Clinical Practices e un primo tentativo di armonizzazione tra le procedure regolatorie dei diversi stati membri,re tutti gli aspetti inerenti le sperimentazioni interventistiche con farmaco7.Situazione completamente opposta in Italia, dove l'implementazione della vecchia direttiva aveva causato una emorragia di decreti ministeriali e di altri atti legislativi che difficilmente potevano venire riorganizzati, come accaduto in Spagna, in un unico atto. Uno stato che ha portato, ancora una volta e forse in maniera ancora più complessa di quanto accaduto a inizio millennio, a un lungo processo di riorganizzazione legislativa, avviato con il decreto Lorenzin e ancora molto lontano dall'essere completato con tutti i decreti attuativi necessari.

Recombinant human growth hormone (rhGH) is widely used to treat growth retardation in children. We aimed to examine the effect of rhGH therapy on growth and its impact on allograft function in children with growth retardation after intestinal transplant (IT).

We retrospectively included children younger than 19 years who had received an IT with or without the liver, were diagnosed with growth retardation, and have received rhGH between January 2010 and January 2021. Changes in the patient's anthropometric parameters between baseline and various time points were compared using the paired t-test or Wilcoxon signed-rank test, as appropriate.

Seven patients (all males and prepubertal) received rhGH for the median duration of 2.3 years. The median age at rhGH start was 9.5 years. The median growth velocity z-score improved from -0.95 before treatment to 2.3 (p= .04) and 1.9 (p= .06) after 1 and 2 years of treatment, respectively. The median height-for-age z-score significantly improved from -3.4 at rhGH start to -1.3 (p= .005) at rhGH stop and remained above baseline at the last visit (-2.4, p= .002). The change in the first-year growth velocity was negatively correlated with the change in the second-year growth velocity (r= -.90, p= .04). No serious adverse effects or worsening allograft function were observed.

Severely growth retarded children after IT could benefit from rhGH treatment. A larger, longitudinal study would be warranted to monitor the long-term effect and safety of rhGH and examine predictors of growth response to rhGH therapy in these pediatric IT recipients.

Severely growth retarded children after IT could benefit from rhGH treatment. A larger, longitudinal study would be warranted to monitor the long-term effect and safety of rhGH and examine predictors of growth response to rhGH therapy in these pediatric IT recipients.Inertial microfluidics functions solely based on the fluid dynamics at relatively high flow speed. BRD0539 Thus, channel geometry is the critical design parameter that contributes to the performance of the device. Four basic channel geometries (i.e., straight, expansion-contraction, spiral and serpentine) have been proposed and extensively studied. To further enhance the performance, innovative channel design through combining two or more geometries is promising. This work explores embedding periodic concave and convex obstacle microstructures in sinusoidal channels and investigates their influence on particle inertial focusing and separation. The concave obstacles could significantly enhance the Dean flow and tune the flow range for particle inertial focusing and separation. Based on this finding, we propose a cascaded device by connecting two sinusoidal channels consecutively for rare cell separation. The concave obstacles are embedded in the second channel to adapt its operational flow rates and enable the functional operation of both channels. Polystyrene beads and breast cancer cells (T47D) spiking in the blood were respectively processed by the proposed device. The results indicate an outstanding separation performance, with 3 to 4 orders of magnitude enhancement in purity for samples with a primary cancer cells ratio of 0.01% and 0.001%, respectively. Embedding microstructures as obstacles brings more flexibility to the design of inertial microfluidic devices, offering a feasible new way to combine two or more serial processing units for high-performance separation.

Several leech species of the genera Hirudo, Hirudinaria, and Whitmania are widely used in traditional Chinese medicine (TCM) for the oral treatment of disorders associated with blood stasis. Among them, the non-hematophagous leech Whitmania pigra expresses a variety of components that have the potential to act on the vertebrate blood coagulation system.

Whether the thrombin inhibitor hirudin, probably the most prominent leech-derived anticoagulant, is actually present in Whitmania pigra, is still a matter of debate. To answer that open question was the aim of the study.

We identified several putative hirudin-encoding sequences in transcriptome data of Whitmania pigra. Upon gene synthesis and molecular cloning the respective recombinant proteins were expressed in Escherichia coli, purified, processed, and eventually functionally characterized for thrombin-inhibitory potencies in coagulation assays.

We were successful in the identification and functional characterization of several putative hirudins in Whitmania pigra. Some, but not all, of these factors are indeed thrombin inhibitors. Whitmania pigra hence expresses both hirudins (factors that inhibit thrombin) and hirudin-like factors (that do not or only very weakly inhibit thrombin). Furthermore, we revealed the exon/intron structures of the corresponding genes. Coding sequences of some putative hirudins of Whitmania pigra were present also in transcriptome datasets of Hirudo nipponia, a hematophagous leech that is likewise used in TCM.

Based on both structural and functional data we provide very strong evidence for the expression of hirudins in Whitmania pigra. This is the first description of hirudins in a non-hematophagous leech.

Based on both structural and functional data we provide very strong evidence for the expression of hirudins in Whitmania pigra. This is the first description of hirudins in a non-hematophagous leech.Chromophores that generate singlet oxygen (1O2) in water are essential to developing noninvasive disease treatments using photodynamic therapy (PDT). A facile approach for formation of stable colloidal nanoparticles of 1O2 photosensitizers, which exhibit aggregation enhanced 1O2 generation in water toward applications as PDT agents, is reported. Chromophore encryption within a fuchsonarene macrocyclic scaffold insulates the photosensitizer from aggregation induced deactivation pathways, enabling a higher chromophore density than typical 1O2 generating nanoparticles. Aggregation enhanced 1O2 generation in water is observed, and variation in molecular structure allows for regulation of the physical properties of the nanoparticles which ultimately affects the 1O2 generation. In vitro activity and the ability of the particles to pass through the cell membrane into the cytoplasm is demonstrated using confocal fluorescence microscopy with HeLa cells. Photosensitizer encryption in rigid macrocycles, such as fuchsonarenes, offers new prospects for the production of biocompatible nanoarchitectures for applications involving 1O2 generation.

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