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Climate change poses a series of challenges to water management to satisfy society's current and future needs. Considering water an essential resource for life, this research is dedicated to comparing the environmental impacts caused by the conventional water supply system and Conventional Water Supply system complemented with rainwater harvesting, considering in the first one not only the components of the municipal public supply, but also the hydraulic components of the residences until the point of use. A life cycle assessment—LCA—was conducted for the two systems, considering them from the catchment to the point of use. This methodology quantifies environmental impacts throughout the product or process life cycle to obtain sustainable options, from raw material extraction to ultimate disposal. The results expose that the hybrid system represents an increase in environmental impacts. However, at a building scale, this increase was very small, and this can be seen as favorable to the hybrid system due to the benefit it brings. The seven percent reduction in water demand over the conventional system can represent significant relief in regions that already have water stress as a reality. This study has the potential to guide managers and designers of public water policies, providing data for a better decision-making process. [ABSTRACT FROM AUTHOR]

This year's review on bioactivation and reactivity began as a part of the annual review on biotransformation and bioactivation led by Cyrus Khojasteh (see references). Increased contributions from experts in the field led to the development of a stand alone edition for the first time this year focused specifically on bioactivation and reactivity. Our objective for this review is to highlight and share articles which we deem influential and significant regarding the development of covalent inhibitors, mechanisms of reactive metabolite formation, enzyme inactivation, and drug safety. Based on the selected articles, we created two sections: (1) reactivity and enzyme inactivation, and (2) bioactivation mechanisms and safety (Table 1). Several biotransformation experts have contributed to this effort from academic and industry settings. Table 1. Articles covered in this review. Title First author Source Reactivity & enzyme inactivation 1 The inactivation of human aldehyde oxidase 1 by hydrogen peroxide and superoxide. C Garrido Drug Metab Dispos 49:729–735, 2021 2 Icotinib induces mechanism-based inactivation of recombinant human CYP3A4/5 possibly via heme destruction by ketene intermediate. C Sun Drug Metab Dispos 49:892–901, 2021 3 Evobrutinib, a covalent Bruton's tyrosine kinase inhibitor: Mass balance, elimination route, and metabolism in healthy participants. H Scheible Clin Transl Sci 14: 2420–2430, 2021 Bioactivation mechanisms & safety 4 Metabolic activation of atomoxetine mediated by cytochrome P450 2D6. Y You Chem Res Toxicol 34:2135–2144, 2021 5 Mechanism-based insights into removing the mutagenicity of aromatic amines by small structural alterations. I Shamovsky J Med Chem 64: 8545–8563, 2021 6 Investigating the mechanism of trimethoprim-induced skin rash and liver injury. Y Cao J Toxicol Sci 180:17–25, 2021 7 Bioactivation of clozapine by mitochondria of the murine heart: Possible cause of cardiotoxicity. E Arzuk Toxicology 447: 152628, 2021 8 CYP2C9 and 3A4 play opposing roles in bioactivation and detoxification of diphenylamine NSAIDs. Mary Alexandra Schleiff Biochem Pharmacol 194:114824, 2021 9 Metabolic activation and cytotoxicity of labetalol hydrochloride mediated by sulfotransferases. L Yang Chem Res Toxicol 34:1612–1618, 2021 10 Cytochrome P450 binding and bioactivation of tumor-targeted duocarmycin agents. AG Bart Drug Metab Dispos 50:49–57, 2022 11 Preclinical metabolism and disposition of an orally bioavailable macrocyclic FXIa inhibitor. SA Chacko Xenobiotica 51:933–948, 2021 12 Identification of an isoform catalyzing the CoA conjugation of nonsteroidal anti-inflammatory drugs and the evaluation of the expression levels of acyl-CoA synthetases in the human liver. H Hashizume Biochem Pharmacol 183:114303, 2021 13 Identification and characterization of in vitro, in vivo, and reactive metabolites of tandutinib using liquid chromatography ion trap mass spectrometry. NS Al-Shakliah Anal Methods 13: 399–410, 2021 14 Idiosyncratic drug-induced liver injury: Mechanistic and clinical challenges. A Jee Int J Mol Sci 22: 2954, 2021 [ABSTRACT FROM AUTHOR]

The two primary species of the bacterium Bartonella appear to affect different body systems and have different risk factors. Bartonella (B.) infection was first discovered in AIDS patients and causes angiomatosis and peliosis. Angiomatosis tends to affect skin, bone and other organs whereas peliosis primarily affects the liver and spleen. A study of 49 patients with either of these conditions found that about half were infected with B. henselae and half with B. quintana. Peliosis was strongly linked to B. henselae and angiomatosis was linked to B. quintana. Cat exposure was linked to B. henselae infection whereas lice exposure was linked to B. quintana.

Colostrum is the first product secreted by the mammary gland to transfer immunity to the newborn, especially through immunoglobulins (Ig) G. Melatonin is an immunomodulatory factor and there is evidence that it has a direct effect on IgG production. To evaluate the effects of melatonin treatment during pregnancy, litter size and offspring sex on colostrum quality, sixty pregnant Rasa Aragonesa ewes were divided into three groups: one group received a melatonin implant at the third month of pregnancy (3M, n = 13), another group at the fourth month (4M, n = 18) and the remaining ewes were not implanted (Control, C, n = 29). Immediately after lambing, a sample of colostrum was collected and IgG, crude protein and fat content analysed. Timing of melatonin implantation (p <.001), and offspring sex (p <.01) had a significant effect on IgG concentration. Colostrum of treated ewes had a higher mean (±SEM) IgG concentration than that of the control ewes (55.54 ± 3.09 and 49.50 ± 4.36 mg/ml, respectively; p <.05), mainly because the concentration in the 4M group was significantly (p <.001) higher than it was in the other groups. The relationship between lamb sex and IgG (p <.01) and %CP (p <.05) was evident in singletons (ewes with a male lamb: 54.57 ± 5.37 mg IgG/ml, 15.42 ± 0.82%CP; ewes with a female lamb: 34.66 ± 4.30 mg/ml, 13.18 ± 0.73%CP). The presence of a female in the litter was associated with significantly (p <.01) lower colostrum IgG levels (litters with at least one female: 49.33 ± 3.42 mg/ml; litters with no females: 58.24 ± 4.00 mg/ml). Among 4M ewes, female foetuses had significantly (p <.01) lower IgG levels whether they carried singletons or multiple lambs. In conclusion, treatment with melatonin implants at the fourth month of pregnancy resulted in a higher colostrum quality based on IgG concentration. [ABSTRACT FROM AUTHOR]

Nosema ceranae is a worldwide distributed midgut parasite of western honey bees, leading to dwindling colonies and their collapse. As a treatment, only fumagillin is available, causing issues like resistance and hampered bee physiology. This study aimed to evaluate ApiHerb® and Api-Bioxal® as treatments against N. ceranae. The efficacy was tested using two qPCR methods based on the 16S rRNA and Hsp70 genes. In addition, these methods were compared for their aptitude for the quantification of the infection. For this, 19 colonies were selected based on the presence of N. ceranae infections. The colonies were divided into three groups: treated with ApiHerb, Api-Bioxal with previous queen caging and an untreated control. All colonies were sampled pre- and post-treatment. The bees were analyzed individually and in duplicate with both qPCR methods. All bees in the pre-treatment tested positive for N. ceranae. Both treatments reduced the abundance of N. ceranae, but ApiHerb also decreased the prevalence of infected bees. Analysis with the 16S rRNA method resulted in several orders of magnitude more copies than analysis with the Hsp70 method. We conclude that both products are suitable candidates for N. ceranae treatment. From our analysis, the qPCR method based on the Hsp70 gene results as more apt for the exact quantification of N. ceranae as is needed for the development of veterinary medicinal products [ABSTRACT FROM AUTHOR]

Pectin-based hydrogels for biomedical applications have attracted recent attention due to their low cost, large availability of the materials, and high levels of biocompatibility. Specifically, periodate-oxidized pectin has been combined with chitosan and gelatin to form different structures. However, hydrogen peroxide-mediated oxidation of pectin has not been studied for this application; furthermore, there is little information on the effect of the degree of oxidation on hydrogel characteristics nor has the feasibility of these systems as controlled drug delivery matrices been explored. Thus, the present work proposes to study the properties of gelatin-peroxide-oxidized pectin hydrogels as drug delivery systems in wound dressing applications. Combinations of pectin at different degrees of oxidation (high, low, and native pectin) and gelatin were analyzed and tested by swelling properties, reswelling from xerogel and aerogel forms, SEM, FTIR, and drug release. It was determined that hydrogels that contained oxidized pectin had improved swelling ratios and stability, at 32°C, compared to those with native pectin and only gelatin. The porosity of the oxidized pectin hydrogels allowed to have sustained and high release rates, which would make them an attractive alternative for wound dressings. [ABSTRACT FROM AUTHOR]

The Central America Four (CA-4) region, comprising Guatemala, Honduras, El Salvador, and Nicaragua, is the largest low- and middle-income country region in the Western Hemisphere, with over 36 million inhabitants. The CA-4 nations share a common geography, history, language, and development indices, and unified with open borders in 2006. The growing CA-4 cancer burden among the noncommunicable diseases is expected to increase 73% by 2030, which argues for a regional approach to cancer control. This has driven efforts to establish population-based cancer registries as a central component of the cancer control plans. The involvement of international and academic partners in an array of initiatives to improve cancer information and control in the CA-4 has accelerated over the past several years. Existing data underscore that the infectious cancers (cervical, stomach, and liver) are a particular burden. All four countries have committed to establishing regional population-based cancer registries and have advanced significantly in pediatric cancer registration. The challenges common to each nation include the lack of national cancer control plans and departments, competing health priorities, lack of trained personnel, and sustainability strategies. General recommendations to address these challenges are outlined. The ongoing regional, international, and academic cooperation has proven helpful and is expected to continue to be a powerful instrument to contribute to the design and implementation of long-term national cancer control plans. [ABSTRACT FROM AUTHOR]

The Central America Four (CA-4) region, comprising Guatemala, Honduras, El Salvador, and Nicaragua, is the largest low- and middle-income country region in the Western Hemisphere, with over 36 million inhabitants. The CA-4 nations share a common geography, history, language, and development indices, and unified with open borders in 2006. The growing CA-4 cancer burden among the noncommunicable diseases is expected to increase 73% by 2030, which argues for a regional approach to cancer control. This has driven efforts to establish population-based cancer registries as a central component of the cancer control plans. The involvement of international and academic partners in an array of initiatives to improve cancer information and control in the CA-4 has accelerated over the past several years. Existing data underscore that the infectious cancers (cervical, stomach, and liver) are a particular burden. All four countries have committed to establishing regional population-based cancer registries and have advanced significantly in pediatric cancer registration. The challenges common to each nation include the lack of national cancer control plans and departments, competing health priorities, lack of trained personnel, and sustainability strategies. General recommendations to address these challenges are outlined. The ongoing regional, international, and academic cooperation has proven helpful and is expected to continue to be a powerful instrument to contribute to the design and implementation of long-term national cancer control plans. [ABSTRACT FROM AUTHOR]

In March, 2009, the report of patients with influenza by a virus with a genetic combination that had never been identified, was seen to be on the increase in Mexico. H1N1 Influenza A virus of swine origin, was a new epidemic. Three months after the epidemiologic alert declared by the Mexican government, the World Health Organization (WHO) reported 6,225 confirmed cases in 73 countries. This event prompted the WHO to declare a pandemia on June 11th. We did a retrospective study of the clinical files of 36 children with a confirmed result of H1N1 influenza A from March to November 2009 at the Instituto Nacional de Enfermedades Respiratorias (INER). The age of the patients ranged from 9 months to 14 years.16.7% of them had history of exposure to H1N1 influenza A; 33% had been vaccined against seasonal influenza for 2008 to 2009. Patients presented with cough (100%), fever (83%), respiratory distress (83%), rhinorrhea (69.5%). Relevant laboratory findings were: leukopenia (44%), lymphocytopenia (88%), monocytosis (55), elevated lactic dehydrogenase (91%); and creatininephosphokinase (56%). Three patients died. [ABSTRACT FROM AUTHOR]

Mammalian aldehyde oxidases (AOX) are molybdo-flavoenzymes of pharmacological and pathophysiologic relevance that are involved in phase I drug metabolism and, as a product of their enzymatic activity, are also involved in the generation of reactive oxygen species. So far, the physiologic role of aldehyde oxidase 1 in the human body remains unknown. The human enzyme hAOX1 is characterized by a broad substrate specificity, oxidizing aromatic/aliphatic aldehydes into their corresponding carboxylic acids, and hydroxylating various heteroaromatic rings. The enzyme uses oxygen as terminal electron acceptor to produce hydrogen peroxide and superoxide during turnover. Since hAOX1 and, in particular, some natural variants produce not only H 2 O 2 but also high amounts of superoxide, we investigated the effect of both ROS molecules on the enzymatic activity of hAOX1 in more detail. We compared hAOX1 to the high-O 2 .- -producing natural variant L438V for their time-dependent inactivation with H 2 O 2 /O 2 .- during substrate turnover. We show that the inactivation of the hAOX1 wild-type enzyme is mainly based on the production of hydrogen peroxide, whereas for the variant L438V, both hydrogen peroxide and superoxide contribute to the time-dependent inactivation of the enzyme during turnover. Further, the level of inactivation was revealed to be substrate-dependent: using substrates with higher turnover numbers resulted in a faster inactivation of the enzymes. Analysis of the inactivation site of the enzyme identified a loss of the terminal sulfido ligand at the molybdenum active site by the produced ROS during turnover. SIGNIFICANCE STATEMENT: This work characterizes the substrate-dependent inactivation of human aldehyde oxidase 1 under turnover by reactive oxygen species and identifies the site of inactivation. The role of ROS in the inhibition of human aldehyde oxidase 1 will have a high impact on future studies., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Nosema ceranae is a worldwide distributed midgut parasite of western honey bees, leading to dwindling colonies and their collapse. As a treatment, only fumagillin is available, causing issues like resistance and hampered bee physiology. This study aimed to evaluate ApiHerb ® and Api-Bioxal ® as treatments against N. ceranae . The efficacy was tested using two qPCR methods based on the 16S rRNA and Hsp70 genes. In addition, these methods were compared for their aptitude for the quantification of the infection. For this, 19 colonies were selected based on the presence of N. ceranae infections. The colonies were divided into three groups: treated with ApiHerb, Api-Bioxal with previous queen caging and an untreated control. All colonies were sampled pre- and post-treatment. The bees were analyzed individually and in duplicate with both qPCR methods. All bees in the pre-treatment tested positive for N. ceranae . Both treatments reduced the abundance of N. ceranae , but ApiHerb also decreased the prevalence of infected bees. Analysis with the 16S rRNA method resulted in several orders of magnitude more copies than analysis with the Hsp70 method. We conclude that both products are suitable candidates for N. ceranae treatment. From our analysis, the qPCR method based on the Hsp70 gene results as more apt for the exact quantification of N. ceranae as is needed for the development of veterinary medicinal products.