The clinical efficacy of a sublingual monomeric allergoid at different maintenance doses: a randomized controlled trial

Sublingual immunotherapy is widely recognized as a viable treatment for allergic rhinitis and asthma, but the optimal dosage is still under debate, expecially with modified allergens. We assessed the clinical effects of a monomeric allergoid across 3 different maintenance doses in mite-monosensitized patients with rhinitis and intermittent asthma. Eighty-nine patients allergic to HDM were randomized to 3 maintenance doses of monomeric allergoid (Lais®, Lofarma) or medications only. All the patients recorded their symptoms and rescue drug consumption in a diary card from November to February. Additionally, nasal eosinophil count, spirometry and methacholine bronchial challenge were performed at the beginning of the study and after 3 years. The symptom scores showed a clear improvement in all the three active arms versus baseline and versus the controls, irrespective of the dose. Likewise, a similar improvement versus baseline was seen for nasal inflammation and bronchial hyperreactivity. The SLIT with monomeric allergoids produces clinically significant results across a wide range of doses. The absence of significant side effects, even at high doses, is probably due to their low level of allergenicity

Serum 25-hydroxyvitamin D measurement: Comparative evaluation of three automated immunoassays

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Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms

Bile acids have been shown to inhibit human (h) carbonic anhydrases (CA, EC 4.2.1.1) along the gastrointestinal tract, including hCA II. The elucidation of the hormonal inhibition mechanism of the bile acid cholate to hCA II was provided in 2014 by X-ray crystallography. Herein, we extend the inhibition study to a wealth of steroids against four relevant hCA isoforms. Steroids displaying pendants and functional groups of the carboxylate, phenolic or sulfonate types appended at the tetracyclic ring were shown to inhibit the cytosolic CA II and the tumor-associated, transmembrane CA IX in a medium micromolar range (38.9–89.9 µM). Docking studies displayed the different chemotypes CA inhibition mechanisms. Molecular dynamics (MD) gave insights on the stability over time of hyocholic acid binding to CA II

Optimisation by Design of Experiment of Benzimidazol-2-One Synthesis under Flow Conditions

A novel flow-based approach for the preparation of benzimidazol-2-one (1) scaffold by the 1,1 `-carbonyldiimidazole (CDI)-promoted cyclocarbonylation of o-phenylenediamine (2) is reported. Starting from a preliminary batch screening, the model reaction was successfully translated under flow conditions and optimised by means of design of experiment (DoE). The method allowed the efficient preparation of this privileged scaffold and to set up a general protocol for the multigram-scale preparation in high yield, purity, and productivity, and was successfully applied for the multigram flow synthesis of N-(2-chlorobenzyl)-5-cyano-benzimidazol-2-one, which is a key synthon for hit-to-lead explorations in our anti-inflammatory drug discovery program

Remote sensing reveals fire-driven facilitation of a C4 rhizomatous alien grass on a small Mediterranean volcanic island

Volcanic islands are special ecosystems for studying biogeographical and evolutionary processes. Occasional disturbance events, such as eruptions, tsunami or big fires, can represent major drivers of such processes leading to biotic sterilisation or major changes in island biotas. In this study, through remotely sensed data, we investigated the intensity and the extent of a large fire event that occurred on the small volcanic island of Stromboli (Aeolian archipelago, Italy) on 25 and 26 May 2022, to assess the short-term effect of fire damages on local plant communities. For this purpose, two different spectrally sensitive indices, i. e. the differential Normalised Burned Index (dNBR) and the Normalised Difference Vegetation Index (NDVI), were used. The dNBR was also used to quantify the extent of early-stage vegetation recovery, dominated by Saccharum biflorum Forssk. (Poaceae), a rhizomatous C4 perennial grass of paleotropical origin. The burned area was estimated to have an extension of around 337.83 ha, corresponding to 27.7 % of the island surface and to 49.8 % of Stromboli’s vegetated area. On the one hand, this event considerably damaged the native plant communities, hosting many species of high biogeographic interest. On the other hand, Saccharum biflorum clearly benefited from arson. In fact, it showed a very high vegetative performance after burning, being able to exert unchallenged dominance in the early stages of the post-fire succession, reaching within a few months stem density values that are only slightly lower than those of the unburned stands. Our results confirm the complex and probably synergic impact of different human disturbances (recurrent fires, introduction of invasive alien plants) on the structure and the functioning of natural ecosystems on small volcanic islands. The natural dynamics of such ecosystems is dependent on the complex relation between successional processes and the intensity and frequency of natural or anthropogenic disturbance, which can regulate mid- and long-term response of Saccharum. In fact, although the expansion of Saccharum proves to be surprisingly fast, its decline may also be relatively rapid as well, if local vegetation is no more affected by fire. After the abandonment of the agricultural practices in the highest portion of the island, the rewilding process could lead to the replacement of the large beds dominated by this invasive grass by native woody vegetation within a few decades

Oral Health-Related Quality of Life and Mental Health Impairment in Patients Affected by Medication-Related Osteonecrosis of the Jaws: A Case–Control Pilot Study

In the present case–control study, the impact of medication-related osteonecrosis of the jaws (MRONJ) on patients’ oral health-related quality of life (OHRQoL), overall quality of life (QoL), and psychological status was evaluated using a set of questionnaires. These questionnaires included the Oral Health Impact Profile-14 (OHIP-14), the Short Form 36 Health Survey Questionnaire (SF-36), and the hospital anxiety and depression scale (HADS). A total of 25 MRONJ patients and 25 controls were included in the study. The results showed that MRONJ patients had a significantly poorer OHRQoL (OHIP-14 score p-value: 0.003) and lower general QoL, particularly in the domains of “physical functioning”, “physical role”, “body pain”, “general health”, and “vitality” in the SF-36 questionnaire (p-values: 0.001, 0.001, 0.013, 0.001, and 0.020). Although there were no significant differences between the groups in the SF-36 domains of “social functioning”, “emotional role”, and “mental health”, the mean sub-scores of the HADS, specifically the depression and anxiety scores (HADS-D and HADS-A), were significantly higher in MRONJ patients (p-values: 0.002 and 0.009). However, the “mental health” domain of the SF-36 questionnaire showed a correlation with both HADS-A and HADS-D scores (p-values: 0.003 and 0.031). Therefore, a comprehensive clinical examination of MRONJ patients should include the assessment of OHRQoL, overall QoL, and psychological profile using different questionnaires. This approach aims to gather detailed information about patients’ physical and psychological well-being, enabling the development of tailored treatments

The Clinical Efficacy of a Sublingual Monomeric Allergoid at Different Maintenance Doses: A Randomized Controlled Trial

Sublingual immunotherapy is widely recognized as a viable treatment for allergic rhinitis and asthma, but the optimal dosage is still under debate, expecially with modified allergens. We assessed the clinical effects of a monomeric allergoid across 3 different maintenance doses in mite-monosensitized patients with rhinitis and intermittent asthma. Eighty-nine patients allergic to HDM were randomized to 3 maintenance doses of monomeric allergoid (Lais®, Lofarma) or medications only. All the patients recorded their symptoms and rescue drug consumption in a diary card from November to February. Additionally, nasal eosinophil count, spirometry and methacholine bronchial challenge were performed at the beginning of the study and after 3 years. The symptom scores showed a clear improvement in all the three active arms versus baseline and versus the controls, irrespective of the dose. Likewise, a similar improvement versus baseline was seen for nasal inflammation and bronchial hyperreactivity. The SLIT with monomeric allergoids produces clinically significant results across a wide range of doses. The absence of significant side effects, even at high doses, is probably due to their low level of allergenicity