Topical and Intralesional Immunotherapy for the Management of Basal Cell Carcinoma.

Basal Cell Carcinoma (BCC) is the most common type of cancer among the white population. Individuals with fair skin have an average lifetime risk of around 30% for developing BCC, and there is a noticeable upward trend in its incidence rate. The principal treatment objectives for BCC involve achieving the total excision of the tumor while maximizing the preservation of function and cosmesis. Surgery is considered the treatment of choice for BCC for two main reasons: it allows for the highest cure rates and facilitates histological control of resection margins. However, in the subgroup of patients with low-risk recurrence or medical contraindications for surgery, new non-surgical treatment alternatives can provide an excellent oncological and cosmetic outcome. An evident and justified instance of these local therapies occurred during the COVID-19 pandemic, a period when surgical interventions carried out in hospital settings were not a viable option.

Chlamydomonas reinhardtii and Microbacterium forte sp. nov., a mutualistic association that favors sustainable hydrogen production.

A naturally occurring multispecies bacterial community composed of Bacillus cereus and two novel bacteria (Microbacterium forte sp. nov. and Stenotrophomonas goyi sp. nov.) has been identified from a contaminated culture of the microalga Chlamydomonas reinhardtii. When incubated in mannitol- and yeast extract-containing medium, this bacterial community can promote and sustain algal hydrogen production up to 313 mL H2·L-1 for 17 days and 163.5 mL H2·L-1 for 25 days in high-cell (76.7 µg·mL-1 of initial chlorophyll) and low-cell density (10 µg·mL-1 of initial chlorophyll) algal cultures, respectively. In low-cell density algal cultures, hydrogen production was compatible with algal growth (reaching up to 60 µg·mL-1 of chlorophyll). Among the bacterial community, M. forte sp. nov. was the sole responsible for the improvement in hydrogen production. However, algal growth was not observed in the Chlamydomonas-M. forte sp. nov. consortium during hydrogen-producing conditions (hypoxia), suggesting that the presence of B. cereus and S. goyi sp. nov. could be crucial to support the algal growth during hypoxia. Still, under non­hydrogen producing conditions (aerobiosis) the Chlamydomonas-M. forte sp. nov. consortium allowed algal growth (up to 40 µg·mL-1 of chlorophyll) and long-term algal viability (>45 days). The genome sequence and growth tests of M. forte sp. nov. have revealed that this bacterium is auxotroph for biotin and thiamine and unable to use sulfate as sulfur source; it requires S-reduced forms such as cysteine and methionine. Cocultures of Chlamydomonas reinhardtii and M. forte sp. nov. established a mutualistic association: the alga complemented the nutrient deficiencies of the bacterium, while the bacterium released ammonium (0.19 mM·day-1) and acetic acid (0.15 mM·day-1) for the alga. This work offers a promising avenue for photohydrogen production concomitant with algal biomass generation using nutrients not suitable for mixotrophic algal growth.

Factors associated with blood product requirements during the transoperative period in pediatric patients.

BACKGROUND: The efficiency of blood products (BP) requisition in elective non-cardiac surgeries is inherently complex. Moreover, it is aggravated in the pediatric population. This study aimed to identify the factors associated with using less than the requested BP during the transoperative period in pediatric patients undergoing elective non-cardiac surgery. METHODS: We conducted a cross-sectional comparative study including 320 patients undergoing elective non-cardiac surgery for whom BPs were requested. Low requirements were considered when less than 50% of the requested amount or no BPs were used, and high requirements when more than the requested amount was used. The Mann-Whitney's U test was applied for comparative analysis, and multiple logistic regression was used to adjust for factors associated with lower requirements. RESULTS: The median age of the patients was 3 years. From 320 patients, 68.1% (n = 218) received less than the requested amount of BP, while only 1.25% (n = 4) received more than the requested amount of BP. Factors associated with transfusion of less than the requested BPs were prolonged clotting time (odds ratio (OR) = 2.66) and anemia (OR = 0.43). CONCLUSIONS: Factors associated with lower than requested BP transfusion were prolonged clotting time and anemia.

INTRODUCCIÓN: La eficiencia de la solicitud de productos sanguíneos (PS) en las cirugías electivas no cardiacas es, de por sí, compleja. No obstante, se agrava para la población pediátrica. El objetivo de este estudio fue identificar los factores asociados con la utilización de una cantidad de PS menor a la solicitada durante el transoperatorio en pacientes pediátricos sometidos a cirugía electiva no cardiaca. MÉTODOS: Se realizó un estudio transversal comparativo donde se incluyeron 320 pacientes sometidos a cirugía electiva no cardiaca para quienes se solicitaron PS. Los requerimientos de hemoderivados se consideraron como menores cuando no se utilizaron o se utilizó menos del 50% de lo solicitado y como mayores cuando se utilizó una cantidad mayor a la solicitada. Se aplicó la prueba U de Mann-Whitney para el análisis comparativo y regresión logística múltiple para ajustar los factores asociados a la presencia de menores requerimientos. RESULTADOS: La mediana para la edad de los pacientes fue de 3 años. Se transfundió una cantidad de PS menor a la solicitada en el 68.1% (n = 218) de los pacientes, mientras que se transfundió una cantidad mayor a la solicitada solo en el 1.25% de los pacientes (n = 4). Los factores asociados con la transfusión de una cantidad de PS menor a la solicitada fueron tiempos de coagulación alargados (TCA) (razón de momios (RM) = 2.66) y anemia (RM = 0.43). CONCLUSIONES: Los factores asociados a una transfusión de PS inferior a la solicitada fueron el tiempo de coagulación prolongado y la anemia.

Factors associated with blood product requirements during the transoperative period in pediatric patients / Factores asociados a los requerimientos de productos sanguíneos durante el transoperatorio en pacientes pediátricos

Abstract Background: The efficiency of blood products (BP) requisition in elective non-cardiac surgeries is inherently complex. Moreover, it is aggravated in the pediatric population. This study aimed to identify the factors associated with using less than the requested BP during the transoperative period in pediatric patients undergoing elective non-cardiac surgery. Methods: We conducted a cross-sectional comparative study including 320 patients undergoing elective non-cardiac surgery for whom BPs were requested. Low requirements were considered when less than 50% of the requested amount or no BPs were used, and high requirements when more than the requested amount was used. The Mann-Whitney's U test was applied for comparative analysis, and multiple logistic regression was used to adjust for factors associated with lower requirements. Results: The median age of the patients was 3 years. From 320 patients, 68.1% (n = 218) received less than the requested amount of BP, while only 1.25% (n = 4) received more than the requested amount of BP. Factors associated with transfusion of less than the requested BPs were prolonged clotting time (odds ratio (OR) = 2.66) and anemia (OR = 0.43). Conclusions: Factors associated with lower than requested BP transfusion were prolonged clotting time and anemia.

Resumen Introducción: La eficiencia de la solicitud de productos sanguíneos (PS) en las cirugías electivas no cardiacas es, de por sí, compleja. No obstante, se agrava para la población pediátrica. El objetivo de este estudio fue identificar los factores asociados con la utilización de una cantidad de PS menor a la solicitada durante el transoperatorio en pacientes pediátricos sometidos a cirugía electiva no cardiaca. Métodos: Se realizó un estudio transversal comparativo donde se incluyeron 320 pacientes sometidos a cirugía electiva no cardiaca para quienes se solicitaron PS. Los requerimientos de hemoderivados se consideraron como menores cuando no se utilizaron o se utilizó menos del 50% de lo solicitado y como mayores cuando se utilizó una cantidad mayor a la solicitada. Se aplicó la prueba U de Mann-Whitney para el análisis comparativo y regresión logística múltiple para ajustar los factores asociados a la presencia de menores requerimientos. Resultados: La mediana para la edad de los pacientes fue de 3 años. Se transfundió una cantidad de PS menor a la solicitada en el 68.1% (n = 218) de los pacientes, mientras que se transfundió una cantidad mayor a la solicitada solo en el 1.25% de los pacientes (n = 4). Los factores asociados con la transfusión de una cantidad de PS menor a la solicitada fueron tiempos de coagulación alargados (TCA) (razón de momios (RM) = 2.66) y anemia (RM = 0.43). Conclusiones: Los factores asociados a una transfusión de PS inferior a la solicitada fueron el tiempo de coagulación prolongado y la anemia.

Chlamydomonas-Methylobacterium oryzae cooperation leads to increased biomass, nitrogen removal and hydrogen production.

In the context of algal wastewater bioremediation, this study has identified a novel consortium formed by the bacterium Methylobacterium oryzae and the microalga Chlamydomonas reinhardtii that greatly increase biomass generation (1.22 g L-1·d-1), inorganic nitrogen removal (>99%), and hydrogen production (33 mL·L-1) when incubated in media containing ethanol and methanol. The key metabolic aspect of this relationship relied on the bacterial oxidation of ethanol to acetate, which supported heterotrophic algal growth. However, in the bacterial monocultures the acetate accumulation inhibited bacterial growth. Moreover, in the absence of methanol, ethanol was an unsuitable carbon source and its incomplete oxidation to acetaldehyde had a toxic effect on both the alga and the bacterium. In cocultures, both alcohols were used as carbon sources by the bacteria, the inhibitory effects were overcome and both microorganisms mutually benefited. Potential biotechnological applications in wastewater treatment, biomass generation and hydrogen production are discussed.

OK, thanks! A new mutualism between Chlamydomonas and methylobacteria facilitates growth on amino acids and peptides.

Nitrogen is a key nutrient for land plants and phytoplankton in terrestrial and aquatic ecosystems. The model alga Chlamydomonas reinhardtii can grow efficiently on several inorganic nitrogen sources (e.g. ammonium, nitrate, nitrite) as well as many amino acids. In this study, we show that Chlamydomonas is unable to use proline, hydroxyproline and peptides that contain these amino acids. However, we discovered that algal growth on these substrates is supported in association with Methylobacterium spp., and that a mutualistic carbon-nitrogen metabolic exchange between Chlamydomonas and Methylobacterium spp. is established. Specifically, the mineralization of these amino acids and peptides by Methylobacterium spp. produces ammonium that can be assimilated by Chlamydomonas, and CO2 photosynthetically fixed by Chlamydomonas yields glycerol that can be assimilated by Methylobacterium. As Chlamydomonas is an algal ancestor to land plants and Methylobacterium is a plant growth-promoting bacterium, this new model of mutualism may facilitate insights into the ecology and evolution of plant-bacterial interactions and design principles of synthetic ecology.

The Chlamydomonas reinhardtii molybdenum cofactor enzyme crARC has a Zn-dependent activity and protein partners similar to those of its human homologue.

The ARC (amidoxime reducing component) proteins are molybdenum cofactor (Moco) enzymes named hmARC1 and hmARC2 (human ARCs [hmARCs]) in humans and YcbX in Escherichia coli. They catalyze the reduction of a broad range of N-hydroxylated compounds (NHC) using reducing power supplied by other proteins. Some NHC are prodrugs or toxic compounds. YcbX contains a ferredoxin (Fd) domain and requires the NADPH flavin reductase CysJ to reduce NHC. In contrast, hmARCs lack the Fd domain and require a human cytochrome b5 (hCyt b5) and a human NADH Cyt b5 reductase (hCyt b5-R) to reduce NHC. The ARC proteins in the plant kingdom are uncharacterized. We demonstrate that Chlamydomonas reinhardtii mutants defective in Moco biosynthesis genes are sensitive to the NHC N(6)-hydroxylaminopurine (HAP). The Chlamydomonas reinhardtii ARC protein crARC has been purified and characterized. The six Chlamydomonas Fds were isolated, but none of them are required by crARC to reduce HAP. We have also purified and characterized five C. reinhardtii Cyt b5 (crCyt b5) and two flavin reductases, one that is NADPH dependent (crCysJ) and one that is NADH dependent (crCyt b5-R). The data show that crARC uses crCyt b5-1 and crCyt b5-R to reduce HAP. The crARC has a Zn-dependent activity, and the presence of Zn increases its V(max) more than 14-fold. In addition, all five cysteines of crARC were substituted by alanine, and we demonstrate that the fully conserved cysteine 252 is essential for both Moco binding and catalysis. Therefore, it is proposed that crARC belongs to the sulfite oxidase family of Moco enzymes.

Transcriptional regulation of CDP1 and CYG56 is required for proper NH4+ sensing in Chlamydomonas.

The assimilation of inorganic nitrogen is an essential process for all plant-like organisms. In the presence of ammonium and nitrate as nitrogen sources, Chlamydomonas reinhardtii preferentially assimilates ammonium and represses the nitrate assimilation pathway through an unknown mechanism that in part involves the guanylate cyclase CYG56. It is demonstrated that cells not only respond quantitatively to the NH(4)(+) signal but are also able to sense a balance between both nitrogen sources. This quantitative response was altered in a collection of mutants that were partially insensitive to NH(4)(+). In one of these mutants, reduced function of a gene named CDP1 encoding a cysteine domain-containing protein was genetically linked to NH(4)(+) insensitivity. Alteration of CYG56 or CDP1 transcription was detected in several mutants, and combined down-regulation of both genes seemed to enhance the incapacity to sense NH(4)(+) properly. These results suggest that transcriptional regulation of CYG56 and CDP1 are central and independent steps of the NH(4)(+) signalling pathway.