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Gingerols represent the main bioactive compounds in ginger drugs mostly Zinigiber officinale (F. Zingebraceae) and account for the biological activities and the strong/pungent flavor in ginger. Ginger (Z. officinale) rhizome is one of the most valued herbal drugs for ailments’ treatment in many ayurvedic medicine asides from its culinary applications as a spice. Gingerols and their dehydrated products shogaols are phenolic phytochemicals found in members of the Zingiberaceae family and account for most of their effects including anti-inflammatory and anticancer activities. This review entails most of the novel trends related to the extraction, optimization, and formulations of gingerols and shogaols to insure best recoveries and efficacies from their natural resources. Further, it presents a comprehensive overview of the different analytical approaches for the determination of gingerols/shogaols’ levels in nutraceuticals to ensure highest quality and for their detection in body fluids for proof of efficacy.

Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans.

In this study, the response of atmospheric electrical and meteorological variables at three different sites of Argentina are studied during the total solar eclipse of December 14, 2020: Valcheta (100% darkening), Buenos Aires (73%) and El Leoncito (71%). The reduction in solar irradiance caused by the solar eclipse was expected to directly affect the near-surface electric field, known as the potential gradient (PG), through a reduction in turbulence and an increase in air conductivity. From the analysis of the observed meteorological parameters (temperature, relative humidity, and wind), no effects on the PG were observed that can be unequivocally attributed to this event based solely on boundary layer dynamics. The prevailing synoptic situation altered the response that the boundary layer could have given, namely, a clear drop in radiation, particularly at Valcheta, which was very close to a frontal zone and had occasional cloud coverage and reports of atmospheric suspended dust. PG measurements at Valcheta during the eclipse showed PG values several orders of magnitude higher and of opposite sign to the global daily mean fair weather (FW) PG curve and the local FW-PG curves calculated at CITEDEF (940 km away) and CASLEO (1200 km away). The PG values at Valcheta were shown to be more closely related to disturbed weather conditions than FW. On the contrary, at the other two locations studied, CITEDEF and CASLEO, further north and more distant from the frontal zone, the observed PG values on the day of the eclipse showed a higher consistency with the local daily mean FW-PG curves. A comparison between the FW-PG local curves at these two sites and the evolution of PG during the day of the eclipse, however, reveals a drop in PG values during the eclipse.

Cell therapy with polyclonal regulatory T cells (Tregs) has been translated into the clinic and is currently being tested in transplant recipients and patients suffering from autoimmune diseases. Moreover, building on animal models, it has been widely reported that antigen-specific Tregs are functionally superior to polyclonal Tregs. Among various options to confer target specificity to Tregs, genetic engineering is a particularly timely one as has been demonstrated in the treatment of hematological malignancies where it is in routine clinical use. Genetic engineering can be exploited to express chimeric antigen receptors (CAR) in Tregs, and this has been successfully demonstrated to be robust in preclinical studies across various animal disease models. However, there are several caveats and a number of strategies should be considered to further improve on targeting, efficacy and to understand the in vivo distribution and fate of CAR-Tregs. Here, we review the differing approaches to confer antigen specificity to Tregs with emphasis on CAR-Tregs. This includes an overview and discussion of the various approaches to improve CAR-Treg specificity and therapeutic efficacy as well as addressing potential safety concerns. We also discuss different imaging approaches to understand the in vivo biodistribution of administered Tregs. Preclinical research as well as suitability of methodologies for clinical translation are discussed.

Objective: This study examined acculturation with positive alcohol expectancies (PAE) and alcohol use intentions among college-bound Latinas using a bidimensional (ie U.S. acculturation/enculturation) and bidomain (ie behaviors/values) acculturation framework. Participants: A total of 298 Latina young adults between 18 and 20 years old were included in this analysis. Methods: Data were collected the summer before participants began college for the first time. We used an online survey to assess acculturation, PAE, and alcohol use expectancies. Results: Path analyses showed that U.S. acculturation values were related to more PAE and alcohol use intentions. U.S. acculturation behaviors were related to more alcohol use intentions, and the pathway was moderated by PAE. There was also an interaction between U.S. acculturation and enculturation behaviors predicting alcohol use intentions. Conclusion: This study sheds light on how acculturating Latina young women think about alcohol use prior to beginning college, which is an opportune window for targeted prevention programs.

Nonisocyanate polyurethanes (NIPUs) and NIPU nanocomposites (NIPU-NCs) were developed from renewable sources. NIPUs were synthesized from a sustainable precursor, castor oil cyclic carbonate (CO-CC), via polyaddition with linalool diamine (LDA) at 110 °C. NIPU properties improved upon the incorporation of 0.5 wt% multiwalled carbon nanotubes (MWCNTs) via covalent (amine-functionalised MWCNTs) and non-covalent (pristine and oxidized MWCNTs) methods. These formulations resulted in the NIPU nanocomposites NIPU-MWCNT-NH2, NIPU-MWCNTs and NIPU-MWCNT-COOH. The physicochemical, thermal and morphological properties of NIPU and NIPU-NCs were studied via multiple techniques such as FTIR, NMR, XRD, TGA, DSC, SEM, water contact angle analysis, XPS and optical microscopy. These samples were applied for coating applications on a mild steel substrate (MST) and glass slides to study antifouling, anticorrosion and UV shielding. Thermal analyses of NIPUs and NIPU-NCs revealed good thermal stability with an appropriate glass transition (Tg) and onset degradation (Td) temperature. Indeed, water contact angle values showed hydrophilic properties, which prompt applications in marine coatings. Biodegradation studies implied that the structural network retained its stability even after immersion for 45 days in a PBS medium. Additionally, NIPUs and NIPU-MWCNT-NH2 demonstrated enhanced UV shielding capability. Finally, NIPU-MWCNT-NH2 exhibited anticorrosion with an impedance modulus ‖Z‖ of 7.43 × 102 (Ω cm2) and essential antifouling properties as well as significantly reduced algae adhesion to 3.143 million per mL. [ABSTRACT FROM AUTHOR]

Objective: This study examined acculturation with positive alcohol expectancies (PAE) and alcohol use intentions among college-bound Latinas using a bidimensional (ie U.S. acculturation/enculturation) and bidomain (ie behaviors/values) acculturation framework. Participants: A total of 298 Latina young adults between 18 and 20 years old were included in this analysis. Methods: Data were collected the summer before participants began college for the first time. We used an online survey to assess acculturation, PAE, and alcohol use expectancies. Results: Path analyses showed that U.S. acculturation values were related to more PAE and alcohol use intentions. U.S. acculturation behaviors were related to more alcohol use intentions, and the pathway was moderated by PAE. There was also an interaction between U.S. acculturation and enculturation behaviors predicting alcohol use intentions. Conclusion: This study sheds light on how acculturating Latina young women think about alcohol use prior to beginning college, which is an opportune window for targeted prevention programs. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic exposed healthcare providers to a psychological burden, especially those on the front lines. Objective: This study aimed to high light the risk factors contributed to psychological pain among healthcare providers (HCP) during the COVID -19 pandemic in Egypt. Methods: This cross-sectional study was conducted on 430 pediatric HCP (from March 2021 to January 2022) who responded to an online survey that included general questions (sociodemographic information, the professional role, and possible changes in job duties), and validated psychometric tools: General Health Questionnaire-12 Items (GHQ-12), the Beck Anxiety Inventory, and the Beck Depression Inventory-II. Results: The prevalence of anxiety and depression among pediatricians was 28% and 23.7% respectively, among nurses was 53.4% and 52.6% respectively and among other included HCP it was 18.6% and 23.7% respectively. This study showed a high prevalence of anxiety and depression among HCP during the COVID-19 pandemic. Females and nurses were the most vulnerable. Reduction of the monthly income and insufficiency of personal protective equipments were of the highest risk factors creating psychological burden. Conclusion: regular psychological risk assessments of healthcare staff should be conducted, particularly during crisis situations.

Diabetic nephropathy results from chronic (or uncontrolled) hyperglycemia and is the leading cause of kidney failure. The kidney’s glomerular podocytes are highly susceptible to diabetic injury and subsequent non-reversible degeneration. We generated a human induced pluripotent stem (iPS) cell-derived model of diabetic podocytopathy to investigate disease pathogenesis and progression. The model recapitulated hallmarks of podocytopathy that precede proteinuria including retraction of foot processes and podocytopenia (detachment from the extracellular matrix (ECM)). Moreover, hyperglycemia-induced injury to podocytes exacerbated remodeling of the ECM. Specifically, mature podocytes aberrantly increased expression and excessively deposited collagen (IV)α1α1α2 that is normally abundant in the embryonic glomerulus. This collagen (IV) imbalance coincided with dysregulation of lineage-specific proteins, structural abnormalities of the ECM, and podocytopenia – a mechanism not shared with endothelium and is distinct from drug-induced injury. Intriguingly, repopulation of hyperglycemia-injured podocytes on decellularized ECM scaffolds isolated from healthy podocytes attenuated the loss of synaptopodin (a mechanosensitive protein associated with podocyte health). These results demonstrate that human iPS cell-derived podocytes can facilitate in vitro studies to uncover the mechanisms of chronic hyperglycemia and ECM remodeling and guide disease target identification.

Abstract Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.

El examen de rutina de los donantes de órganos para detectar la infección por el virus de la inmunodeficiencia humana (HIV) ha hecho que la transmisión del virus mediante el trasplante de órganos sea poco común. Sin embargo, a pesar de las pruebas de detección de rutina, la transmisión del HIV continúa siendo un riesgo del trasplante de órganos ya que, a diferencia de los tejidos, los órganos sólidos no se pueden procesar, desinfectar, ni modificar para inactivar patógenos infecciosos. A continuación, se describe un caso de posible transmisión de HIV por trasplante de órganos de un donante previamente seronegativo a dos de sus receptores.

Abstract Ensuring the quality control of active pharmaceutical ingredients is crucial for drug products being introduced into the market. Even for established drugs, it is necessary to maintain a cutting-edge impurity control system. To analyze caffeine and chlorphenoxamine hydrochloride in their binary mixture, as well as theophylline and chlorphenoxamine N-oxide as related substances, a reversed phase-high performance liquid chromatography combined with a diode array detector system was created. The chromatographic separation was conducted using a C18 X-select Waters® column. The mobile phase consisted of 20.0 mM potassium dihydrogen phosphate modified to pH 3 with o-phosphoric acid and methanol. A gradient elution program was adopted at a flow rate of 1.3 mL/min and detected at a wavelength of 222 nm. The present methodology demonstrates a concentration ranging from 2–60, 1–80, 0.5–20 to 0.4–20 µg/mL for chlorphenoxamine hydrochloride, caffeine, chlorphenoxamine N-Oxide and theophylline, respectively. Chlorphenoxamine N-Oxide, being an impurity of chlorphenoxamine was prepared by refluxing intact drug with 5% H2O2 for 24 h at 100 °C. One of the objectives of the analytical community is to promote the adoption of green analysis methods, which involve the development of environmentally friendly techniques. The levels of greenness and whiteness were evaluated using four specific tools: Eco-Scale System, GAPI, AGREE, and RGB tool. Furthermore, we have evaluated the greenness of the analytical method presented and compared its performance and greenness to that of the approach described in the literature. In this study, results from CPX and CAF analysis were compared to those obtained in a previous study. The result shows that there is no notable variation in precision and accuracy. The proposed method was validated in accordance with the requirements of ICH.

Egypt is negotiating with Ethiopia regarding the construction of the Grand Ethiopian Renaissance Dam (GERD) on the Nile River. This research employs Negotiation theory combined with the role of power and Transboundary Water Interaction concept to understand the negotiation process Egypt carried out. The research findings show that Egypt, using its power that comprises material, bargaining and ideational power, tries to maintain its hegemony in the region. Egypt succeeded in inviting third parties such as the US, World Bank and UNSC in the negotiation process. Political dynamics in the region and internal instability after the 2011 Egyptian Revolution influenced Egypt's strength in its negotiations with Ethiopia. Thus, the interaction is related to contest and compliance. The development of GERD in Ethiopia is seen as a contest for the hegemonic situation, while Egypt is trying to create compliance with Ethiopia. Egypt seeks to create compliance with the status quo through some mechanisms: coercive, utilitarian, normative, and ideological hegemonic. Although the two countries compete with and obey each other, they still collaborate and negotiate to resolve the GERD problem. The interaction between these two during the negotiation process can be categorized as a neutral interaction with low conflict – low cooperation category.