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Background: Cold agglutinin syndrome (CAS) is a hemolytic anemia mediated by antibodies, mainly IgM, whose maximum activity occurs at 4 °C. It happens secondary to infectious, autoimmune or neoplastic diseases, due to the formation of antibodies that cross-react against erythrocyte antigens, particularly of the I system. Here, we describe a case of CAS associated to Epstein-Barr virus (EBV) reactivation in a patient with primary human immunodeficiency virus (HIV) infection. Clinical case: 22-year old man with no medical history, hospitalized due to mononucleosis and anemic syndrome. Hemoglobin of 3.7 g/dL and elevation of lactate dehydrogenase were documented. In the peripheral blood smear it was observed spherocytosis, polychromasia and nucleated erythrocytes. EBV infection was confirmed with serology and viral load, as well as seronegative HIV infection with positive viral load. The C3d monospecific direct antiglobulin test was positive and an irregular antibody screening revealed the presence of an anti-I antibody. The patient received transfusion support and conservative treatment, with remission of the symptoms 2 weeks after admission. Conclusions: Cold agglutinin syndrome is a rare, potentially fatal complication of infectious mononucleosis, which should be considered in the face of findings suggestive of hemolysis in order to initiate support measures in a timely manner.

Introducción: el síndrome por aglutininas frías (SAF) es una anemia hemolítica mediada por anticuerpos principalmente de tipo IgM, cuya máxima actividad se da a 4 °C. Se presenta en el contexto de enfermedades infecciosas, autoinmunes o neoplásicas por la formación de anticuerpos que tienen reacción cruzada contra antígenos eritrocitarios, particularmente del sistema I. En este trabajo presentamos un caso de SAF asociado a reactivación del virus de Epstein-Barr (VEB) en un paciente con primoinfección por el virus de la inmunodeficiencia humana (VIH). Caso clínico: hombre de 22 años, sin antecedentes patológicos, hospitalizado por síndrome mononucleósico y anémico. Presentó hemoglobina de 3.7 g/dL y elevación de lactato deshidrogenasa. En el frotis de sangre periférica se observó esferocitosis, policromasia y eritrocitos nucleados. Se confirmó infección por VEB con serología y carga viral, así como infección por VIH seronegativa, con carga viral positiva. La prueba de antiglobulina directa monoespecífica a C3d fue positiva y el rastreo de anticuerpos irregulares demostró un anticuerpo anti-I. El paciente recibió soporte transfusional y tratamiento conservador, con remisión del cuadro a las 2 semanas de su ingreso. Conclusiones: el SAF es una complicación poco frecuente de la mononucleosis infecciosa, potencialmente mortal, la cual debe ser considerada ante hallazgos sugestivos de hemólisis con la finalidad de iniciar medidas de soporte de forma oportuna.

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Bell pepper plants are sensitive to environmental changes and are significantly affected by abiotic factors such as UV-B radiation and cold, which reduce their yield and production. Various approaches, including omics data integration, have been employed to understand the mechanisms by which this crop copes with abiotic stress. This study aimed to find metabolic changes in bell pepper stems caused by UV-B radiation and cold by integrating omic data. Proteome and metabolome profiles were generated using liquid chromatography coupled with mass spectrometry, and data integration was performed in the plant metabolic pathway database. The combined stress of UV-B and cold induced the accumulation of proteins related to photosynthesis, mitochondrial electron transport, and a response to a stimulus. Further, the production of flavonoids and their glycosides, as well as affecting carbon metabolism, tetrapyrrole, and scopolamine pathways, were identified. We have made the first metabolic regulatory network map showing how bell pepper stems respond to cold and UV-B stress. We did this by looking at changes in proteins and metabolites that help with respiration, photosynthesis, and the buildup of photoprotective and antioxidant compounds.

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BACKGROUND: Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). METHODS: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. RESULTS: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. CONCLUSION: We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.

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Due to the low temperature, the Antarctic marine environment is challenging for protein functioning. Cold-adapted organisms have evolved proteins endowed with higher flexibility and lower stability in comparison to their thermophilic homologs, resulting in enhanced reaction rates at low temperatures. The Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) genome is one of the few examples of coexistence of multiple hemoglobin genes encoding, among others, two constitutively transcribed 2/2 hemoglobins (2/2Hbs), also named truncated Hbs (TrHbs), belonging to the Group II (or O), annotated as PSHAa0030 and PSHAa2217. In this work, we describe the ligand binding kinetics and their interrelationship with the dynamical properties of globin Ph-2/2HbO-2217 by combining experimental and computational approaches and implementing a new computational method to retrieve information from molecular dynamic trajectories. We show that our approach allows us to identify docking sites within the protein matrix that are potentially able to transiently accommodate ligands and migration pathways connecting them. Consistently with ligand rebinding studies, our modeling suggests that the distal heme pocket is connected to the solvent through a low energy barrier, while inner cavities play only a minor role in modulating rebinding kinetics.

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Cold tumors lack antitumor immunity and are resistant to therapy, representing a major challenge in cancer medicine. Because of the immunosuppressive spirit of the tumor microenvironment (TME), this form of tumor has a low response to immunotherapy, radiotherapy, and also chemotherapy. Cold tumors have low infiltration of immune cells and a high expression of co-inhibitory molecules, such as immune checkpoints and immunosuppressive molecules. Therefore, targeting TME and remodeling immunity in cold tumors can improve the chance of tumor repression after therapy. However, tumor stroma prevents the infiltration of inflammatory cells and hinders the penetration of diverse molecules and drugs. Nanoparticles are an intriguing tool for the delivery of immune modulatory agents and shifting cold to hot tumors. In this review article, we discuss the mechanisms underlying the ability of nanoparticles loaded with different drugs and products to modulate TME and enhance immune cell infiltration. We also focus on newest progresses in the design and development of nanoparticle-based strategies for changing cold to hot tumors. These include the use of nanoparticles for targeted delivery of immunomodulatory agents, such as cytokines, small molecules, and checkpoint inhibitors, and for co-delivery of chemotherapy drugs and immunomodulatory agents. Furthermore, we discuss the potential of nanoparticles for enhancing the efficacy of cancer vaccines and cell therapy for overcoming resistance to treatment.

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BACKGROUND: Increased thermogenic activity has shown to be a promising target for treating and preventing obesity and type 2 diabetes (T2DM). Little is known about the muscular influence on nonshivering thermogenesis (NST), and it remains unclear whether physical training and potential metabolic improvements could be associated with changes in this type of thermogenic activity. OBJECTIVE: The present study aimed to assess muscular NST activity in overweight and T2DM before and after a combined training period (strength training followed by aerobic exercise). METHODS: Nonshivering cold-induced 18-fluoroxyglucose positron emission computed tomography (18F-FDG PET/CT) was performed before and after 16 weeks of combined training in 12 individuals with overweight and T2DM. The standard uptake value (SUV) of 18F-FDG was evaluated in skeletal muscles, the heart and the aorta. RESULTS: Muscles in the neck region exhibit higher SUV pre- and posttraining. Furthermore, a decrease in glucose uptake by the muscles of the lower and upper extremities and in the aorta was observed after training when adjusted for brown adipose tissue (BAT). These pre-post effects are accompanied by increased cardiac SUV and occur concurrently with heightened energy expenditure and metabolic improvements. CONCLUSIONS: Muscles in the neck region have greater metabolic activity upon exposure to cold. In addition, combined training appears to induce greater NST, favoring the trunk and neck region compared to limbs based on joint work and adaptations between skeletal muscles and BAT.

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Grains germinate, dry, and then undergo crushing before being combined with hot water to yield a sweet and viscous liquid known as wort. To enhance flavor and aroma compounds while maintaining a lower alcohol content, cold water is utilized during wort production without increasing its density. Recent years have witnessed a surge in demand for beverages with reduced alcohol content, reflecting shifting consumer preferences towards healthier lifestyles. Notably, consumers of low-alcohol beers seek products that closely mimic traditional beers. In response, batches of low-alcohol beer were meticulously crafted using a cold extraction method with room temperature water, resulting in a beer with 1.11% alcohol by volume (ABV). Sensory evaluations yielded a favorable score of 27 out of 50, indicating adherence to style standards and absence of major technical flaws. Furthermore, electronic taste profiling revealed a striking similarity between the low-alcohol beer and the benchmark International Pale Lager style, exemplified by commercial beers (5 and 0.03% ABV). Notably, the reduced-alcohol variant boasted lower caloric content compared to both standard and non-alcoholic counterparts. Consequently, the cold extraction approach emerges as a promising technique for producing low-alcohol beers within the International Pale Lager style, catering to evolving consumer preferences and health-conscious trends.

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Introduction: The current study aimed to compare the quality of root canal obturation performed with cold lateral condensation with other obturation techniques. Materials and Methods: Diverse Search was conducted using six electronic/academic databases following PICOS (i.e. population, intervention, control, outcomes, and study design) strategy: (P) Extracted mature permanent teeth; (I) Obturation techniques except for cold lateral condensation; (C) Cold lateral condensation tyechnique; (O) Quality of root canal obturation; and (S) In vitro studies assessing parameters using micro-computed tomography. The statistical method used for the meta-analyses was the "inverse variance DerSimonian-Laird test". The heterogeneity data was calculated using the T2, Cochran Q test, and I2 statistics. Results: Fifteen studies were included for the final analysis; one had a low risk of bias, eight a moderate risk, and six a high risk of bias. Ten studies were selected for meta-analyses; three studies comparing cold lateral condensation with carrier-based gutta-percha techniques [P=0.96; mean difference (MD)=-0.02; confidence interval (CI): (-0.77, 0.73); I2=21%]; three comparing cold lateral condensation with single-cone techniques [P=0.75; MD=-0.39; CI: (-2.77, 1.99); I2=92%]; two comparing cold lateral condensation and thermo-plasticized injectable techniques [P=0.37; MD=5.91; CI: (-7.13,18.94); I2=99%]; and five comparing cold lateral condensation with warm vertical condensation techniques [P<0.0001; MD=5.29; CI=(2.84, 7.74); I2=92%]. The overall effect reported significant results [P=0.0003; MD=2.69; CI=(1.23, 4.16); I2=96%]; favoring fewer voids and gaps for the other used obturation techniques. Conclusions: Cold lateral condensation and single-cone techniques presented no statistical differences. Nonetheless, Warm vertical condensation technique had better results compared to cold lateral condensation.

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Background and Purpose: Studies assessing the costs of the immunobiological cold chain (CC) are scarce. Therefore, the factors that influence the allocation of resources in this process are not known. The objective of this study is to determine the cost of the immunobiological CC. Methods: The Health Economic Assessment study was carried out in Minas Gerais, Brazil, between 2021 and 2022. The unit of analysis was the municipal level of the CC. The perspective of the Public Health System (Sistema Único de Saúde) was considered as a funder, the year 2021 was considered as the time frame, and the period of 1 year was considered as the time horizon of the analysis. Direct medical, nonmedical, and indirect costs were included. A mixed technique was used involving micro- and macrocosting and sensitivity analysis to identify the influence of the main categories on the final cost. Results: The total cost was USD 20,014,545, with nonmedical direct costs being the most representative (61.24%). Human resources were the most influential items, representing 76.43% of the total cost. Conclusions: The most influential items should be those of greatest concern and planned by managers to make the CC more efficient.