Association of drought conditions and heavy rainfalls with the quality of drinking water in Barcelona (2010-2022).

BACKGROUND: Climate change influences the incidence and scope of climate extreme events that affect communities and the environment around the world. In an urban context such as Barcelona, these climate extremes can have a negative impact on drinking water quality. The worsening of drinking water quality can have important repercussions on human health, leading to the appearance of different diseases. OBJECTIVE: Investigate the association between climate extremes, in particular heavy rainfall events and drought conditions, and the drinking water quality in the city of Barcelona from 2010 to 2022. METHODS: We conducted a daily retrospective time-series study using data covering 13 years of daily monitoring of conductivity, nickel, turbidity and trihalomethanes parameters of raw water in the Llobregat River catchment area and treated water in the Drinking Water Treatment Plant (DWTP) Sant Joan Despí. We used river flow as a proxy for drought conditions and heavy rainfall events. We analyzed short-term associations between river flow rate and quality parameters in raw and treated water using generalized linear regression with distributed lag-non-linear models (DLNM). RESULTS: A low flow, as an indicator of drought condition or low rainfall, was significantly associated with an increase in conductivity in raw water and nickel in both raw and treated water. A high flow, as an indicator of heavy rainfall events, was significantly associated with an increase of turbidity in raw water, and a decrease in all other quality parameters. IMPACT STATEMENT: This study provides novel evidence that climate extremes have an impact on the quality of drinking water in urban areas with a Mediterranean climate. The findings of this study are significant because they suggest that as the frequency and intensity of climate extremes increase due to climate change, there will be further challenges in managing and treating drinking water, which could have a detrimental effect on public health. This study serves as an important reminder of the need to strengthen and accelerate adaptation actions in water management to ensure an adequate supply of drinking water that protects the people's health.

Immunity elicited by AMP-encoding plasmids fails to increase the protection of European sea bass against nodavirus.

Antimicrobial peptides (AMPs) are a potent arm of the innate immune system that can directly kill pathogens and induce immunomodulation. In the marine aquaculture, European sea bass (Dicentrarchus labrax L.) is one of the most prosperous species but is highly susceptible to nodavirus (NNV), which produces high rates of mortality in larvae and juvenile stages. Thus, we aimed to evaluate whether AMPs exert immunomodulatory and/or NNV-preventive actions in sea bass. To do this, plasmids encoding the sea bass AMPs dicentracin (pDIC), beta-defensin (pDB1), hepcidin (pHAMP2) or NK-lysin (pNKL) were generated and intramuscularly injected into sea bass juveniles to evaluate their immunomodulatory and anti-NNV roles. Sea bass muscle transcribes the AMPs and produces an increase in their circulating levels, along with an increase of the antibacterial activity. Immune-related gene analysis revealed a great activation of the inflammatory response and the recruitment of neutrophilic granulocytes at the site of injection. However, AMP-encoding plasmids, namely pHAMP2, negatively affected to NNV disease by increasing fish mortality. In conclusion, plasmids encoding AMPs show immunostimulatory effects on European sea bass but do not improve the resistance to NNV.

Comparison of criteria for determining appropriateness of antibiotic prescribing in nursing homes.

BACKGROUND: Measuring the appropriateness of antibiotic prescribing in nursing homes remains a challenge. The revised McGeer criteria, which are widely used to conduct infection surveillance in nursing homes, were not designed to assess antibiotic appropriateness. The Loeb criteria were explicitly designed for this purpose but are infrequently used outside investigational studies. The extent to which the revised McGeer and Loeb criteria overlap and can be used interchangeably for tracking antibiotic appropriateness in nursing homes remains insufficiently studied. METHODS: We conducted a cross-sectional chart review study in 5 Wisconsin nursing homes and applied the revised McGeer and Loeb criteria to all nursing home-initiated antibiotic treatment courses. Kappa (κ) statistics were employed to assess level of agreement overall and by treatment indications. RESULTS: Overall, 734 eligible antibiotic courses were initiated in participating nursing homes during the study period. Of 734 antibiotic courses, 372 (51%) satisfied the Loeb criteria, while only 211 (29%) of 734 satisfied the revised McGeer criteria. Only 169 (23%) of 734 antibiotic courses satisfied both criteria, and the overall level of agreement between them was fair (κ = 0.35). When stratified by infection type, levels of agreement between the revised McGeer and Loeb criteria were moderate for urinary tract infections (κ = 0.45), fair for skin and soft-tissue infections (0.36), and slight for respiratory tract infections (0.17). CONCLUSIONS: Agreement between the revised McGeer and Loeb criteria is limited, and nursing homes should employ the revised McGeer and Loeb criteria for their intended purposes. Studies to establish the best method for ongoing monitoring of antibiotic appropriateness in nursing homes are needed.

Phenolic compounds of blueberries (Vaccinium spp) as a protective strategy against skin cell damage induced by ROS: A review of antioxidant potential and antiproliferative capacity.

The skin is a tissue with a high metabolic activity that acts as a protective layer for the internal organs of the body. This tissue is exposed to a variety of damaging agents, including reactive oxygen species (ROS), which can lead to oxidative damage to various macromolecules, disrupting vital cellular processes and increasing mutations. A situation referred to as oxidative stress occurs when a large amount of oxidants exceeds the capacity of the antioxidant defense system. Oxidative stress is considered a contributory factor to the aging process and the pathogenesis of various skin diseases, including cancer. Several current studies seek to identify new natural compounds with properties that mitigate the harmful effects of ROS, thereby acting as blockers or suppressors of the carcinogenesis process. This review briefly presents the relationship between ultraviolet radiation, ROS, and skin damage; and summarizes the in vitro and in vivo experimental evidence of the chemopreventive effect on skin cancer of phenolic compounds from blueberries (Vaccinium spp). Although several studies addressed the topic of bioactive compounds and their activities as possible anticancer agents, none have focused on the antioxidative action and antiproliferative effects on skin cancer of phenolic compounds derived from blueberries.

Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug.

The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.

High frequency of mutant thiopurine S-methyltransferase genotypes in Mexican patients with systemic lupus erythematosus and rheumatoid arthritis.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are treated with immunosuppressive purine analogs, 6-mercaptopurine/6-thioguanine/azathiopurine, which are inactivated by thiopurine S-methyltransferase (TPMT). Non-synonymous polymorphisms in TPMT are associated with increased risk of adverse effects in patients treated with thiopurines. This study aimed to determine the frequency of the most common mutant TPMT alleles in Mexican patients with SLE (a prototype autoimmune disease) and RA (one of the most common autoimmune diseases in Mexico). Five hundred fifty-three consecutive patients from Central Mexico with SLE (178) and RA (375) were included. Subjects were genotyped to identify TPMT*2 (rs1800462), TPMT*3A (rs1800460 and rs1142345), TPMT*3B (rs1800460), and TPMT*3C (rs1142345) mutant alleles. DNA samples were assayed with the 5' exonuclease technique and TaqMan probes. Mutant alleles were detected in 6.2 and 5.2% of SLE and RA cases, respectively. Of note, 12.4% of SLE cases and 10.1% of RA cases carried mutant genotypes. Among those, the null genotype (TPMT*2/*3A, 0.3%) and the TPMT*3B (0.5%) and TPMT*3C (1.0%) alleles were found in RA, but not SLE cases. Mexican SLE cases displayed the highest frequency of mutant TPMT genotypes worldwide. TPMT genotyping should be performed for Mexican patients with SLE and RA before prescribing purine analogs.

The PTPN22 R263Q polymorphism confers protection against systemic lupus erythematosus and rheumatoid arthritis, while PTPN22 R620W confers susceptibility to Graves' disease in a Mexican population.

OBJECTIVE: The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves' disease (GD) among Mexican patients. METHODS: We conducted a case-control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals. PTPN22 genotypes were determined using the TaqMan 5' allele discrimination assay. RESULTS: PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004), but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated that this polymorphism is associated with RA susceptibility (OR 4.17, p = 0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR 0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD. CONCLUSIONS: Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.

Dietary Conjugated Linoleic Acid-c9t11 Prevents Collagen-Induced Arthritis, Whereas Conjugated Linoleic Acid-t10c12 Increases Arthritic Severity.

Two conjugated linoleic acid (CLA) isomers, cis-9, trans-11 (CLAc9t11) and trans-10, cis-12 (CLAt10c12), reduce inflammation in a number of animal models, including collagen-induced arthritis (CA). However, little is known about the ability of individual CLA isomers to prevent autoimmune disease onset. Evidence that mixed isomer CLA drives T helper cell (Th) 1 responses suggests that CLA, or a specific isomer, exacerbates onset of Th1 autoimmune diseases. In two experiments, we examined if prior dietary exposure to CLAt10c12 (experiment 1) or CLAc9t11 (experiment 2) affected the incidence or severity of CA. DBA/1 mice were fed a semi purified diet with either 6% corn oil (CO, w/w), 5.75% CO plus 0.25% CLAt10c12, or 5.5% CO plus 0.5% CLAc9t11 prior to arthritis development. Arthritis incidence and severity, anti-collagen antibodies, paw cytokines, and hepatic fatty acids were measured. CLAt10c12 had no effect on arthritis incidence but increased arthritic severity (42%, P = 0.02); however, CLAc9t11 decreased arthritis incidence 39% compared to CO fed mice (P = 0.01), but had no effect on disease severity. CLAt10c12-induced increase in anti-collagen type II IgG antibodies may be a mechanism by which this isomer increased arthritic severity, and CLAc9t11-induced increase in Th2 paw cytokines (IL-4 and IL-10, P ≤ 0.04) may explain how CLAc9t11 reduced the arthritis incidence. While both isomers are well known to reduce inflammation in arthritic mice, these new data suggest isomer differences when fed prior to autoimmune disease.

Cirrosis biliar primaria: edad inusual de aparición / Primary biliary cirrhosis: unusual age of appearance

La cirrosis biliar primaria es una enfermedad hepática colestásica crónica, lentamente progresiva, caracterizada por la destrucción no supurativa de la vía biliar interlobulillar y septal. Se presenta principalmente en mujeres de edad media, con incidencia de 0.7-49 casos por millón de habitantes. El propósito de estudiar este caso es describir una enfermedad de difícil diagnóstico, dado que las manifestaciones clínicas pueden orientar a una variedad de posibilidades; sumado a esto la baja incidencia y bajo índice de sospecha que dificulta aún más el hallazgo. Caso clínico: se presenta caso de paciente femenina de 24 años, que llegó a la emergencia del Hospital Escuela Universitario por cuadro de diarrea de un mes de evolución, aproximadamente 3-4 episodios por día, de consistencia blanda, color amarillento, sin exacerbantes; prurito generalizado sin predominio de horario. Al examen físico tinte ictérico en piel y mucosas, abdomen simétrico, sin presencia de cicatrices, dolor a la palpación profunda en hipocondrio derecho, hígado palpable 2 cm debajo del reborde costal.El diagnóstico se realizó mediante la detección de anticuerpos antimitocondriales en suero y la realización de una biopsia hepática. Después de iniciado el tratamiento, comenzó a disminuir el tinte ictérico y los niveles de bilirrubinas, la paciente fue dada de alta y continuó el manejo. Conclusión: el tratamiento temprano con ácido ursodesoxicólico, puede detener la progresión de la enfermedad y mejorar el pronóstico. Para los pacientes que muestran respuesta insuficiente, la terapia combinada con bezafibrato usualmente es efectiva...(AU)

Úlceras cutáneas y neuropatía trombótica como manifestaciones iniciales en un paciente con síndrome antifosfolípido / Cutaneous ulcers and thrombotic neuropathy as first manifestations in a patient with antiphospholipid syndrome

Se presenta el caso de un hombre de 34 años con cuadro clínico crónico de úlceras cutáneas y monoparesia inferior izquierda. Electromiografía que evidencia neuropatía sensitiva del nervio fibular superficial izquierdo; estudios ecográficos sin evidencia de enfermedad arteriovenosa. El paciente no presentó mejoría de lesiones cutáneas con inmunosupresión agresiva. En la biopsia de piel y de nervio sural se encontraron trombos y ausencia de infiltrado inflamatorio compatibles con vasculopatía y neuropatía trombóticas. Se documentó la presencia de anticoagulante lúpico, TPT prolongado y anticuerpos anti-B2 glicoproteína 1 positivos.

This following case report describes a 34 years-old man with chronic clinical skin ulcers and left lower monoparesis. Electromyography revealed sensory neuropathy of the left superficial fibular nerve; the ecographic studies showed absence of artery or venous disorder. The patient showed no improvement of skin lesions with aggressive immunosuppression. The biopsy of the skin and the sural nerve reported thrombi and absence of inflammatory infiltrates; findings that support the diagnosis of thrombotic vasculopathy and neuropathy. The presence of lupus anticoagulant, prolonged PTT and positive anti-B2 glycoprotein antibodies were documented.