Overcoming the Drawbacks of Sulpiride by Means of New Crystal Forms

This study aims at developing new multicomponent crystal forms of sulpiride, an antipsychotic drug. The main goal was to improve its solubility since it belongs to class IV of the BCS. Nine new adducts were obtained by combining the active pharmaceutical ingredient with acid coformers: a salt cocrystal and eight molecular salts. In addition, three novel co-drugs, of which two are molecular salts and one is a cocrystal, were also achieved. All samples were characterized in the solid state by complementary techniques (i.e., infrared spectroscopy, powder X-ray diffraction and solid-state NMR). For systems for which it was possible to obtain good-quality single crystals, the structure was solved by single crystal X-ray diffraction (SCXRD). SCXRD combined with solid-state NMR were used to evaluate the ionic or neutral character of the adducts. In vitro dissolution tests of the new crystal forms were performed and all the adducts display remarkable dissolution properties with respect to pure sulpiride

ALADIN laser frequency stability and its impact on the Aeolus wind error

The acquisition of atmospheric wind profiles on a global scale was realized by the launch of the Aeolus satellite, carrying the unique Atmospheric LAser Doppler INstrument (ALADIN), the first Doppler wind lidar in space. One major component of ALADIN is its high-power, ultraviolet (UV) laser transmitter, which is based on an injection-seeded, frequency-tripled Nd:YAG laser and fulfills a set of demanding requirements in terms of pulse energy, pulse length, repetition rate, and spatial and spectral beam properties. In particular, the frequency stability of the laser emission is an essential parameter which determines the performance of the lidar instrument as the Doppler frequency shifts to be detected are on the order of 10^8 smaller than the frequency of the emitted UV light. This article reports the assessment of the ALADIN laser frequency stability and its influence on the quality of the Aeolus wind data. Excellent frequency stability with pulse-to-pulse variations of about 10 MHz (root mean square) is evident for over more than 2 years of operations in space despite the permanent occurrence of short periods with significantly enhanced frequency noise (> 30 MHz). The latter were found to coincide with specific rotation speeds of the satellite's reaction wheels, suggesting that the root cause are micro-vibrations that deteriorate the laser stability on timescales of a few tens of seconds. Analysis of the Aeolus wind error with respect to European Centre for Medium-Range Weather Forecasts (ECMWF) model winds shows that the temporally degraded frequency stability of the ALADIN laser transmitter has only a minor influence on the wind data quality on a global scale, which is primarily due to the small percentage of wind measurements for which the frequency fluctuations are considerably enhanced. Hence, although the Mie wind bias is increased by 0.3 m/s at times when the frequency stability is worse than 20 MHz, the small contribution of 4 % from all Mie wind results renders this effect insignificant (< 0.1 m/s) when all winds are considered. The impact on the Rayleigh wind bias is negligible even at high frequency noise. Similar results are demonstrated for the apparent speed of the ground returns that are measured with the Mie and Rayleigh channel of the ALADIN receiver. Here, the application of a frequency stability threshold that filters out wind observations with variations larger than 20 or 10 MHz improves the accuracy of the Mie and Rayleigh ground velocities by only 0.05 and 0.10 m/s, respectively, however at the expense of useful ground data

Laparoscopic anterior gastropexy for chronic recurrent gastric volvulus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastric volvulus is an uncommon clinical entity, first described by Berti in 1866. It is a rotation of all or part of the stomach through more than 180°. This rotation can occur on the longitudinal (organo-axial) or transverse (mesentero-axial) axis. This condition can lead to a closed-loop obstruction or strangulation. Traditional surgical therapy for gastric volvulus is based on an open approach. Here we report the case of a patient with chronic intermittent gastric volvulus who underwent a successful laparoscopic treatment.</p> <p>Case presentation</p> <p>A 34-year-old woman presented with multiple episodes of recurrent upper abdominal pain associated with retching and vomiting, treated unsuccessfully with intramuscular metoclopramide. Endoscopic examination of the upper digestive tract showed a suspected rotation of the stomach, and a chronic recurrent gastric volvulus was revealed by barium meal. The patient was operated on successfully, with an anterior laparoscopic gastropexy performed as the first surgical approach.</p> <p>Conclusion</p> <p>Experience with laparoscopic anterior gastropexy is limited only to a few described cases. Our patient was clinically and radiologically followed-up for 2 years with no evidence of recurrence, either radiological or symptomatic. Based on this result, laparoscopic gastropexy can be seen and considered as an initial 'gold standard' for the treatment of gastric volvulus.</p

Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge

We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progression. In the present manuscript, we report the generation of a highly aggressive, anti-PD-1 resistant model of a high-grade, Myc-driven B-cell non-Hodgkin’s lymphoma (NHL) that can be controlled in vivo by TT but not by other chemotherapeutic agents, including cytarabine (AraC), platinum (P), and doxorubicin (D). The immunological memory elicited in tumor-bearing mice by TT (but not by other treatments) can effectively control NHL re-challenge even at very high inoculum doses. TT re-shaped the landscape of circulating innate NK cells and adaptive immune cells, including B and T cells, and significantly reduced exhausted CD4+ and CD8+ TIM3+PD-1+ T cells in the spleens of treated mice

Upper gastrointestinal massive bleeding successfully treated intra-operatively with a collagen and thrombin-based high-viscosity gel for haemostasis. Case report

Un paziente di 57 anni è stato ricoverato nel nostro reparto per massiva emorragia digestiva superiore non da varici esofagee. In accordo con le linee guida, il paziente è stato sottoposto ad esame endoscopico precoce (entro 24 ore dall’ingresso), che ha mostrato la fonte del sanguinamento a livello della seconda porzione duodenale. Durante l’endoscopia è stata praticata un’iniezione emostatica con soluzione adrenalinica (epinefrina 1:10.000). A distanza di 8 ore una severa recidiva emorragica con riduzione dei livelli di emoglobina ci ha indotto al trattamento chirurgico d’urgenza. Intraoperativamente è stata portata a termine una gastroresezione seguita dall’applicazione di gel emostatico ad alta viscosità (Floseal®) nella sede dell’emorragia, all’interno del lume duodenale. Questa tecnica ha permesso di ottenere un’emostasi definitiva senza complicazioni a lungo termine. La nostra esperienza suggerisce che l’applicazione intraoperatoria di Floseal® può essere un’alternativa efficace alle tecniche emostatiche tradizionali nel trattamento chirurgico d’urgenza dell’emorragie digestive superiori. Ciò consente di ottenere una più rapida stabilizzazione emodinamica dando la possibilità di eseguire ulteriori tecniche emostatiche

High-power and frequency-stable ultraviolet laser performance in space for the wind lidar on Aeolus

Global acquisition of atmospheric wind profiles using a spaceborne direct-detection Doppler wind lidar is being accomplished following the launch of European Space Agency's Aeolus mission. One key part of the instrument is a single-frequency, ultraviolet laser that emits nanosecond pulses into the atmosphere. High output energy and frequency stability ensure a sufficient signal-to-noise ratio of the backscatter return and an accurate determination of the Doppler frequency shift induced by the wind. This Letter discusses the design of the laser transmitter for the first Doppler wind lidar in space and its performance during the first year of the Aeolus mission, providing valuable insights for upcoming space lidar missions