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The Lean Management had its origin in the 50s in the Japanese automobile industry, and is currently used in different production processes, included those related to pharmaceutical production, for which has raised its application in the manufacture of loperamide HCl-orodispersible tablets (HCl-ODT) under the coordination of the Pharmaceutical Quality System (PQS). A theoretical proposal for process reengineering has been carried out both incorporating and applying the different Lean tools in the industrial manufacturing process of HCl-ODT, and their subsequent integration into the PQS, through each one of the processes stages, such as: weighing, screening, mixing, compression, and packaging, under the compliance of the current legislation of the pharmaceutical industry and in compatibility with what is established in the ICHs within the Quality System, in order to increase the effectiveness and efficiency of the process and its profitability. Lean Management under the coordination of the Pharmaceutical Quality System (PQS), is an excellent strategy for manufacturing loperamide HCl-orodispersible tablets since it improves its Quality System, as well as facilitates compliance with the national and international guides, standards and legislation that are suitable to it.

The Geostationary Environment Monitoring Spectrometer (GEMS) over Asia is the first geostationary Earth orbit instrument in the virtual constellation of sensors for atmospheric chemistry and composition air quality research and applications. For the first time, the hourly observations enable studies of diurnal variation in several important trace gas and aerosol pollutants including nitrogen dioxide (NO2), which is the focus of this work. NO2 is a regulated pollutant and an indicator of anthropogenic emissions in addition to being involved in tropospheric ozone chemistry and particulate matter formation. We present new quantitative measures of NO2 tropospheric column diurnal variation which can be greater than 50 % of the column amount, especially in polluted environments. The NO2 distribution is seen to change hourly and can be quite different from what would be seen by a once-a-day low-Earth-orbit satellite observation. We use GEMS data in combination with TROPOspheric Monitoring Instrument (TROPOMI) satellite and Pandora ground-based remote sensing measurements and Multi-Scale Infrastructure for Chemistry and Aerosols (Version 0, MUSICAv0) 3D chemical transport model analysis to examine the NO2 diurnal variation in January and June 2023 over Northeast Asia and Seoul, South Korea, study regions to distinguish the different emissions, chemistry, and meteorological processes that drive the variation. Understanding the relative importance of these processes will be key to including pollutant diurnal variation in models aimed at determining true pollutant exposure levels for air quality studies. The work presented here also provides a path for investigating similar NO2 diurnal cycles in the new Earth Venture Instrument-1 Tropospheric Emissions: Monitoring Pollution (TEMPO) data over North America, and later over Europe with Sentinel-4.

Abstract Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908–8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by Aspergillus and Penicillium genera present mainly in fruit, cereals and nuts. This study compares the cytotoxicity produced by CPA after 24, 48 and 72 h of exposure using both monolayers and 3D spheroids in human neuroblastoma SH-SY5Y cells. Furthermore, CPA toxicokinetics was evaluated using in silico models. Cytotoxicity increased dose- and time-dependently, as shown by the MTT assay. The lowest CPA IC50 values were found in the monolayer study compared to the 3D spheroids at all exposure times (24 h: 864.01 vs. 1132; 48 h: 437 vs. 1069; 72 h: 392 vs. 567 nM). The CPA exposure on SH-SY5Y spheroid organization and morphology was also studied. Morphological changes, including spheroid disaggregation, were observed after mycotoxin exposure. The in silico methods, SwissADME and admetSAR, were used for short and full ADMEt profiles of CPA. The ADMEt predictive profile shows high gastrointestinal absorption and ability to penetrate the blood–brain barrier. Including in silico studies emphasizes the comprehensive approach to understanding mycotoxin toxicity and risk assessment. By combining in vitro 3D spheroid models with computational simulations, this study aims to provide a holistic perspective on the effects of CPA, enhancing the accuracy and relevance of our findings.

Calcium phosphates (CaPs) and their substituted derivatives encompass a large number of compounds with a vast presence in nature that have aroused a great interest for decades. In particular, hydroxyapatite (HAp, Ca10(OH)2(PO4)6) is the most abundant CaP mineral and is significant in the biological world, at least in part due to being a major compound in bones and teeth. HAp exhibits excellent properties, such as safety, stability, hardness, biocompatibility, and osteoconductivity, among others. Even some of its drawbacks, such as its fragility, can be redirected thanks to another essential feature: its great versatility. This is based on the compound’s tendency to undergo substitutions of its constituent ions and to incorporate or anchor new molecules on its surface and pores. Thus, its affinity for biomolecules makes it an optimal compound for multiple applications, mainly, but not only, in biological and biomedical fields. The present review provides a chemical and structural context to explain the affinity of HAp for biomolecules such as proteins and nucleic acids to generate hybrid materials. A size-dependent criterium of increasing complexity is applied, ranging from amino acids/nucleobases to the corresponding macromolecules. The incorporation of metal ions or metal complexes into these functionalized compounds is also discussed.

Ferric hexacyanoferrate, Fe4 [Fe(CN)6]3 · xH2O, known as Prussian blue (PB), has proven its effectiveness as an antidote in cases of accidental poisoning or poisoning caused by radioactive materials such as cesium (Cs) and thallium (Tl); which due to their solubility in water, when absorbed by the human body, cause serious damage to vital organs. The local development of a drug with PB as an active ingredient arises as a response to the civil and military needs established within the Ministry's pharmacy request for national defense. This fact contemplates the circumstances related to public health protection in the nuclear, radiological, biological and chemical (NRBQ) of the emergency institutions in health and national security. In this paper and by using various analytical techniques, the characterization of the locally synthesized PB with pharmaceutical quality has been described, as a first step to predict its behavior in the preparation of a drug that contains it as an active ingredient.The research findings demonstrate that locally synthesized PB is suitable for use in oral dosage forms, enabling the local development of drug formulations incorporating PB, thus being able to potentially become a main resource in the treatment of Cs and Tl poisoning in any accidental or intended of the population. This development opens up the possibility of creating drug formulations that incorporate PB at a local level, making it a potentially significant resource in the treatment of Cs and Tl poisoning. The ability to locally produce and utilize PB in oral dosage forms could be crucial in addressing cases of accidental or intentional exposure within the population. This advancement not only contributes to the scientific understanding of PB but also holds promising implications for practical applications in public health and emergency situations.

Malakoplakia is a rare granulomatous inflammatory disorder. Its diagnosis depends on histopathological findings; however, high-quality literature regarding proper medical/surgical treatment is lacking. A 38-year-old diabetic female patient was admitted to the emergency room with a history of lower gastrointestinal hemorrhage. Colonoscopy revealed a lesion in the descending colon, and abdominal computed tomography revealed a splenic flexure mass involving the lower pole of the spleen and upper pole of the left kidney. Biopsies confirmed the diagnosis of malakoplakia. After completing antibiotic treatment, a restaging computed tomography revealed a discrete mass increase; hence, the patient underwent laparoscopic en bloc colectomy and partial nephrectomy. Postoperatively, the patient developed a pancreatic fistula, which was successfully treated with percutaneous drainage and antibiotics. The presence of pathognomonic Michaelis-Gutmann inclusions on histopathology is frequently reported as the key to diagnosing malakoplakia. Herein, we present a successful, minimally invasive surgical treatment for colonic malakoplakia.

Prior research has established the anti-apoptotic effects in insect cell cultures of Bombyx mori (B. mori) hemolymph, as well as the heightened production yields of recombinant proteins facilitated by baculovirus vectors in insect cells cultivated in media supplemented with this hemolymph. In this study, we investigated the hemolymph of another Lepidoptera species, Trichoplusia ni (T. ni), and observed similar beneficial effects in insect cells cultivated in media supplemented with this natural substance. We observed enhancements in both production yield (approximately 1.5 times higher) and late-stage cell viabilities post-infection (30–40% higher). Storage-protein 2 from B. mori (SP2Bm) has previously been identified as one of the abundant hemolymph proteins potentially responsible for the beneficial effects observed after the use of B. mori hemolymph-supplemented cell culture media. By employing a dual baculovirus vector that co-expresses the SP2Bm protein alongside the GFP protein, we achieved a threefold increase in reporter protein production compared to a baculovirus vector expressing GFP alone. This study underscores the potential of hemolymph proteins sourced from various Lepidoptera species as biotechnological tools to augment baculovirus vector productivities, whether utilized as natural supplements in cell culture media or as hemolymph-derived recombinant proteins co-expressed by baculovirus vectors.

Abstract We have analyzed Sentinel‐5 Precursor TROPOspheric Monitoring Instrument (TROPOMI) data over the Copperbelt mining region (Democratic Republic of Congo and Zambia). Despite high background values, annual 2019–2022 means of TROPOMI NO2 (nitrogen dioxide) show local enhancements consistent with six point sources (four copper/cobalt mines, two cities) where high‐emission industrial activities take place. We have quantified annual NOx (nitrogen oxides) emissions from these point sources, identified temporal trends in emissions, and found strong correlations with production data from colocated mines and one oil refinery. The Copernicus Atmosphere Monitoring Service Global Anthropogenic (CAMS‐GLOB‐ANT) version 5 inventory underpredicts TROPOMI‐derived emissions and lacks the temporal trends observed in TROPOMI and mine/refinery production. These results demonstrate the potential for satellite monitoring of mining and other industrial activities, often unreported or underestimated, which impact the air quality of local communities. This is particularly important for Africa, where mining is increasing aggressively.

Meloxicam (MX) is a poorly water-soluble drug with severe gastrointestinal side effects. Topical hydrogel of hydroxypropyl guar (HPG) was formulated using a solid dispersion (SD) of MX with hydroxypropyl cellulose (LHPC) as an alternative to oral administration. The development of a solid dispersion with an adequate MX:LHPC ratio could increase the topical delivery of meloxicam. Solid dispersions showed high MX solubility values and were related to an increase in hydrophilicity. The drug/polymer and polymer/polymer interactions of solid dispersions within the HPG hydrogels were evaluated by SEM, DSC, FTIR, and viscosity studies. A porous structure was observed in the solid dispersion hydrogel MX:LHPC (1:2.5) and its higher viscosity was related to a high increase in hydrogen bonds among the –OH groups from LHPC and HPG with water molecules. In vitro drug release studies showed increases of 3.20 and 3.97-fold for hydrogels with MX:LHPC ratios of (1:1) and (1:2.5), respectively, at 2 h compared to hydrogel with pure MX. Finally, a fitting transition from zero to first-order model was observed for these hydrogels containing solid dispersions, while the n value of Korsmeyer–Peppas model indicated that release mechanism is governed by diffusion through an important relaxation of the polymer.

AirCore in situ vertical profiles sample the atmosphere from near the surface to the lower stratosphere, making them ideal for the validation of satellite tropospheric trace gas data. Here we present intercomparison results of AirCore carbon monoxide (CO) measurements with respect to retrievals from MOPITT (Measurements of Pollution In The Troposphere; version 8) and TROPOMI (TROPOspheric Monitoring Instrument), on board the NASA Terra and ESA Sentinel 5-Precursor satellites, respectively. Mean MOPITT/AirCore total column bias values and their standard deviation (0.4 ± 5.5, 1.7 ± 5.6, and 0.7 ± 6.0 for MOPITT thermal-infrared, near-infrared, and multispectral retrievals, respectively; all in %) are similar to results obtained in MOPITT/NOAA aircraft flask data comparisons from this study and from previous validation efforts. MOPITT CO retrievals are systematically validated using in situ vertical profiles from a variety of aircraft campaigns. Because most aircraft vertical profiles do not sample the troposphere's entire vertical extent, they must be extended upwards in order to be usable in validation. Here we quantify, for the first time, the error introduced in MOPITT CO validation by the use of shorter aircraft vertical profiles extended upwards by analyzing validation results of MOPITT with respect to full and truncated AirCore CO vertical profiles. Our results indicate that the error is small, affects mostly upper tropospheric retrievals (at 300 hPa: ∼ 2.6, 0.8, and 3.2 percent points for MOPITT thermal-infrared, near-infrared, and multispectral, respectively), and may have resulted in the overestimation of MOPITT retrieval biases in that region. TROPOMI can retrieve CO under both clear and cloudy conditions. The latter is achieved by quantifying interfering trace gases and parameters describing the cloud contamination of the measurements together with the CO column; then, the reference CO profiles used in the retrieval are scaled based on estimated above-cloud CO rather than on estimated total CO. We use AirCore measurements as the reference to evaluate the error introduced by this approach in cloudy TROPOMI retrievals over land after accounting for TROPOMI's vertical sensitivity to CO (relative bias and its standard deviation = 2.02 % ± 11.13 %). We also quantify the null-space error, which accounts for differences between the shape of TROPOMI reference profiles and that of AirCore measured profiles (for TROPOMI cloudy enull=0.98 % ± 2.32 %).