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Gene therapy holds significant promise as a therapeutic approach for addressing a diverse range of diseases through the suppression of overexpressed proteins and the restoration of impaired cell functions. Developing a nanocarrier that can efficiently load and release genetic material into cells remains a challenge. The primary goal of this study is to develop formulations aimed to enhance the therapeutic potential of GapmeRs through technological approaches. To this end, lipid-polymeric hybrid nanoparticles (LPHNPs) with PLGA, DC-cholesterol, and DOPE-mPEG 2000 were produced by conventional single-step nanoprecipitation (SSN) and microfluidic (MF) methods. The optimized nanoparticles by SSN have a size of 149.9 ± 18.07 nm, a polydispersity index (PdI) of 0.23 ± 0.02, and a zeta potential of (ZP) of 29.34 ± 2.44 mV, while by MF the size was 179.8 ± 6.3, a PdI of 0.24 ± 0.01, and a ZP of 32.25 ± 1.36 mV. Furthermore, LPHNPs prepared with GapmeR-protamine by both methods exhibit a high encapsulation efficiency of approximately 90%. The encapsulated GapmeR is completely released in 24 h. The LPHNP suspensions are stable for up to 6 h in 10% FBS at pH 5.4 and 7.4. By contrast, LPHNPs remain stable in suspension in 4.5% albumin at pH 7.4 for 24 h. Additionally, LPHNPs were successfully freeze-dried using trehalose in the range of 2.5-5% as cryoprotectant The LPHNPs produced by MF and SSN increase, 6 and 12 fold respectively, GapmeR cell uptake, and both of them reduce by 60-70% expression of Tob1 in 48 h.Our study demonstrates the efficacy of the developed LPHNPs as carriers for oligonucleotide delivery, offering valuable insights for their scale up production from a conventional bulk methodology to a high-throughput microfluidic technology., Competing Interests: Declarations. Ethics approval: Not applicable. Competing interests: The authors have non-financial interests to disclose., (© 2024. The Author(s).)

Syneruptive magma mixing is widespread in volcanic eruptions, affecting explosivity and composition of products, but its evidence in basaltic systems is usually cryptic. Here we report direct evidence of mixing between basanitic and tephritic magmas in the first days of the 2021 Tajogaite eruption of Cumbre Vieja, La Palma. Groundmass glass in tephritic tephra from the fifth day of the eruption is locally inhomogeneous, showing micron-scale filamentary structures of Si-poor and Fe-, Mg-rich melt, forming complex filaments attached to bubbles. Their compositional distribution attests the presence of primitive basanitic magma, with compositions similar to late-erupted melts, interacting with an evolved tephritic melt during the first week of the event. From filament morphology, we suggest their generation by dragging and folding of basanitic melt during bubble migration through melt interfaces. Semi-quantitative diffusion modelling indicates that the filamentary structures are short-lived, dissipating in timescales of tens of seconds. In combination with thermobarometric constraints, we suggest a mixing onset by sub-Moho remobilization of a tephritic reservoir by basanite input, followed by turbulent ascent of a mingled magma. In the shallow conduit or lava fountain, bubble nucleation and migration triggered further mingling of the distinct melt-phases. This phenomenon might have enhanced the explosive behaviour of the eruption in such period, where violent strombolian explosions were common., (© 2023. Springer Nature Limited.)

Introduction: Little is known about the clinical significance of the "anti-HBc alone" serological profile (absence of HBsAg and anti-HBs) in HBV infections. The objective of the present study was to estimate the prevalence of the anti-HBc alone immunological profile and the clinical-epidemiological characteristics of patients with this profile., Methods: Prospective, cross-sectional, descriptive study performed in 2002 and including patients with anti-HBc alone (HBsAg-negative, anti-HBs-negative and anti-HBc-positive). All the cases identified underwent the following microbiological tests: IgM anti-HBc, HBeAg, anti-HBe, anti-HDV, anti-HCV, anti-HIV, as well as HBV-DNA testing by qualitative nested-PCR. Furthermore, studies of serum biochemical parameters, blood counts and coagulation, as well as a clinical-epidemiological interview were performed in all patients., Results: Among 3900 patients studied, 195 (5%) presented the anti-HBc alone profile (48% were > 65 years old). Residual anti-HBs (< 10 mUI/mL) was found in 44% of cases and 33% were anti-HBe positive. HCV or HIV coinfection were seen in 38% and 8%, respectively. HBV-DNA was detected in 4.2% (5/120) of cases. Epidemiologically, detection of anti-HBc alone was casual in 60% of patients, whereas the remaining cases had a history of chronic liver disease (82% of these were anti-HCV positive). In a high percentage (63%) the transmission mechanism of HBV infection was unknown (11% intravenous drug abuser, 10% surgery, 6% transfusions)., Conclusion: The anti-HBc alone pattern is a frequent finding, particularly in patients > 65 years old and in HCV or HIV coinfected patients. Although HBV-DNA was detected in a small percentage of cases, this test could be indicated in certain clinical situations (liver disease, coinfection, donors). Furthermore, this profile seems to be related with HCV infection; hence, we consider anti-HCV detection necessary in all patients with anti-HBc alone.

Upper gastrointestinal hemorrhage secondary to gastric varices still has a high death rate. Fourteen patients were admitted to our unit with bleeding gastric varices from November 1989 to August 1991. Endoscopic injection sclerotherapy obtained control of the bleeding in 92.3%; however, recurrences occurred in 33% of these cases in the first 24-48 hours, with a death rate of 50% during the second stage of the upper gastrointestinal hemorrhage. Total mortality rate was 21.4%. Of the fourteen patients, nine exhibited junctional varices, while five hand fundic varices. In ten of the fourteen patients, gastric varices developed during esophageal sclerotherapy. While hospitalized, it was observed that patients with gastric varices in the fundus had more recurrences and mortality, than those located next to the cardio-esophageal junction. Sclerosis of the varices only obtained temporary control of the bleeding with greater frequency of recurrences and mortality.