Efficacy of Centers of Biomedical Research Excellence (CoBRE) grants to build research capacity in underrepresented states.

Federal funding for research has immediate and long-term economic impact. Since federal research funding is regionally concentrated and not geographically distributed, the benefits are not fully realized in some regions of the country. The Established (previously Experimental) Program to Stimulate Competitive Research (EPSCoR) programs at several agencies, for example, the National Science Foundation, and the Institutional Development Award (IDeA) program at the National Institutes of Health were created to increase competitiveness for funding in states with historically low levels of federal funding. The Centers of Biomedical Research Excellence (CoBRE) award program is a component of the IDeA program. The CoBRE grants support research core facilities to develop research infrastructure. These grants also support the research projects of junior investigators, under the guidance of mentoring teams of senior investigators, to develop human resources at these institutions. Few studies have assessed the effectiveness of these programs. This study examines the investment and outcomes of the CoBRE grants from 2000 through 2022. The maturation of junior investigators into independently funded principal investigators is comparable to other mentoring programs supported by NIH. The investment in research cores resulted in substantial research productivity, measured by publications. Despite the successes of individual investigators and increased research infrastructure and productivity, the geographic distribution of federal and NIH research dollars has not changed. These results will be informative in consideration of policies designed to enhance the geographic distribution of federal research dollars.

An assessment tool for evaluating the National Institute of General Medical Sciences COBRE and INBRE mentoring programs.

The National Institute of General Medical Sciences (NIGMS) mandates that its Centers of Biomedical Research Excellence (COBRE) and Institutional Development Award Networks of Biomedical Research Excellence (INBRE) institute formal mentoring programs to promote the core program objective of junior investigator development. Despite this NIGMS requirement, and the many career-related benefits associated with mentoring, few tools exist for purposes of rigorously evaluating COBRE and INBRE mentoring programs. The purpose of this project was to develop a mentoring assessment tool to aid in the evaluation of COBRE and INBRE mentoring programs. In study 1, a list of items comprising the tool was created via a multiphase item generation process based on input received from subject matter experts within the Cognitive and Neurobiological Approaches to Plasticity Center. In study 2, feedback about this tool was solicited from 78 grant directors, mentees, and mentors representing 21 unique COBRE programs and 8 unique INBRE programs from across the United States. The results provide initial evidence that this tool possesses suitable psychometric properties, is a flexible instrument with many potential uses, and represents a valuable resource for helping evaluate COBRE and INBRE mentoring programs. Having a tool for evaluating mentoring can help promote the grant success and career development of junior investigators in COBRE and INBRE programs and help program directors develop more sustainable research centers.

The wide distribution of an extremely thermoacidophilic microorganism in the copper mine at ambient temperature and under acidic condition and its significance in bioleaching of a chalcopyrite concentrate.

Thermoacidophiles can exist in a state of dormancy both in moderate temperatures and even in cold conditions in heap leaching. Sulphide mineral ores such as chalcopyrite produce sulfuric acid when exposed to the air and water. The produced sulfuric acid leads to the decrease of pH and exothermic reactions in heap leaching causing the temperature to increase up to 55°C and the activation of thermoacidophilic microorganisms. The aim of the present study was to isolate indigenous extreme thermoacidophilic microorganisms at ambient temperature from Sarcheshmeh Copper Complex, to adapt them to the high pulp density of a chalcopyrite concentrate, and to determine their efficiency in chalcopyrite bioleaching in order to recover copper. In this study samples were collected at ambient temperature from Sarcheshmeh Copper Complex in Iran. Mixed samples were inoculated into the culture medium for enrichment of the microorganisms. Pure cultures from these enrichments were obtained by subculture of liquid culture to solid media. Morphological observation was performed under the scanning electron microscope. Isolates were adapted to 30% (w/v) pulp density. For the bioleaching test, the experiments were designed with DX7 software. Bioleaching experiments were carried out in Erlenmeyer flasks and a stirred tank reactor. The highest copper recovery in Erlenmeyer flasks was 39.46% with pulp 15%, inoculums 20%, size particle 90µm and 160rpm. The lowest recovery was 3.81% with pulp 20%, inoculums 20%, size particle 40µm and 140rpm after 28 days. In the reactor, copper recovery was 32.38%. Bioleaching residues were analyzed by the X-ray diffraction (XRD) method. The results showed no jarosite (KFe3(SO4)2(OH)6) had formed in the bioleaching experiments. It seems that the antagonistic reactions among various species and a great number of planktonic cells in Erlenmeyer flasks and the stirred tank reactor are the reasons for the low recovery of copper in our study.

Síntesis y uso de histidinato de cobre en niños con enfermedad de Menkes en México.

Menkes disease is a neurodegenerative and lethal pathology caused by gene mutations of the copper-transporting ATP-7A enzyme; it manifests itself by neurological symptoms and connective tissue changes of varying severity. Timely subcutaneous use of copper histidinate (Cu-His) is determinant for quality of life. We report the first experiences in Mexico on Cu-His synthesis and its safe use in 3 cases where hypocupremia and hypoceruloplasminemia were corroborated. With advice of the Hospital for Sick Children of Toronto Canada, we prepared a 500 µg/mL solution. In all three cases were 250 µg of Cu-His applied without relevant undesirable effects for 30 days. Serum copper (Cu, expressed in µg/L) and ceruloplasmin (Cp, in mg/dL) were determined: case 1, Cu days 0 and 30, 8 and 504 µg/L; Cp days 0 and 30, 4 and 10.75 mg/dL; case 2, Cu days 0 and 30, <50 and 502 µg/L; Cp days 0 and 30, 2 and 15 mg/dL; case 3, Cu days 0 and 30, 3 and 84.2 µg/L; Cp days 0 and 30, 4 and 10.7 mg/dL. In Mexico, it is possible to safely synthesize Cu-His and treat MD, which must be intentionally sought.

La enfermedad de Menkes es una patología neurodegenerativa y letal debida a mutaciones génicas de la enzima ATP-7A trasportadora de cobre; se manifiesta por síntomas neurológicos y alteraciones del tejido conectivo de severidad variable. El uso subcutáneo oportuno de histidinato de cobre (Cu-His) es determinante en la calidad de vida. Se reportan las primeras experiencias en México en la síntesis y uso seguro de Cu-His en tres casos en los que corroboramos hipocupremia e hipoceruloplasminemia. Bajo asesoramiento del Hospital for Sick Children, Toronto, Canadá, elaboramos una solución de 500 µg/mL. En los tres casos aplicamos 250 µg de Cu-His, sin efectos indeseables relevantes durante 30 días y observamos las siguientes determinaciones séricas de cobre (Cu en µg/L) y ceruloplasmina (Cp en mg/dL): caso 1, Cu días 0 y 30, 8 y 504 µg/L; Cp días 0 y 30, 4 y 10.75 mg/dL; caso 2, Cu días 0 y 30, < 50 y 502, µg/L; Cp días 0 y 30, 2 y 15 mg/dL; caso 3, Cu días 0 y 30, 3 y 84.2 µg/L; Cp días 0 y 30, 4 y 10.7 mg/dL. En México es posible la síntesis segura de Cu-His y tratar la enfermedad de Menkes, la cual debe ser intencionalmente buscada.

Optimization of laccase production by two strains of Ganoderma lucidum using phenolic and metallic inducers.

Ganoderma lucidum (Curtis) P. Karst is a white rot fungus that is able to degrade the lignin component in wood. The ability of two strains of this species to produce the ligninolytic enzyme laccase was assessed. After the evaluation of induction with heavy metals and phenolic compounds, it was found that among the tested substances, copper and ferulic acid are the best laccase inducers. It was also observed that the two types of inducers (phenolic and metallic) produce different electrophoretic patterns of laccase activity. Optimized concentrations of inducers were obtained through a factorial design and the thermal stability of optimized supernatants was studied at a wide range of acidic pH. We found that the enzyme is more thermostable at higher pH values.

Efficacy of Centers of Biomedical Research Excellence (CoBRE) Grants to Build Research Capacity in Underrepresented States.

Federal funding for research has immediate and long-term economic impact. Since federal research funding is regionally concentrated and not geographically distributed, the benefits are not fully realized in some regions of the country. The Established (previously Experimental) Program to Stimulate Competitive Research (EPSCoR) programs at several agencies, e.g. the National Science Foundation, and the Institutional Development Award (IDeA) program at the National Institutes of Health were created to increase competitiveness for funding in states with historically low levels of federal funding. The Centers of Biomedical Research Excellence (CoBRE) award program is a component of the IDeA program. The CoBRE grants support research core facilities to develop research infrastructure. These grants also support the research projects of junior investigators, under the guidance of mentoring teams of senior investigators, to develop human resources at these institutions. Few studies have assessed the effectiveness of these programs. This study examines the investment and outcomes of the CoBRE grants from 2000 through 2022. The maturation of junior investigators into independently funded principal investigators is comparable to other mentoring programs supported by NIH. The investment in research cores resulted in substantial research productivity, measured by publications. Despite the successes of individual investigators and increase research infrastructure and productivity, the geographic distribution of federal and NIH research dollars has not changed. These results will be informative in consideration of policies designed to enhance the geographic distribution of federal research dollars.

Effect of UV-C disinfection and copper plating on healthcare-associated infections in a NICU with high ESBL infections.

INTRODUCTION: Healthcare-associated infections (HCAIs) in neonates are frequent and highly lethal, in particular those caused by extended spectrum beta-lactamase (ESBL) producing bacteria. We evaluated the beneficial effects of ultraviolet C (UV-C) disinfection and copper adhesive plating on HCAIs in the Neonatal Intensive Care Unit (NICU) of a third level paediatric hospital in Mexico City, both in combination of hand-hygiene (HH) and prevention bundles. METHODS: All NICU patients were included. There were 4 periods (P): P1: HH monitoring and prevention bundles; P2: P1+UV-C disinfection; P3: P2+Copper adhesive plating on frequent-contact surfaces and P4: Monitoring of P3 actions. RESULTS: 552 neonates were monitored during 15,467 patient days (PD). HCAI rates decreased from 11.03/1000 PD in P1 to 5.35/1000 PD in P4 (p=0.006). HCAIs with bacterial isolates dropped from 5.39/1000 PD in PI to 1.79/1000 PD in P4 (p=0.011). UV-C and copper were associated with significant HCAI prevention (RR 0.49, CI95% 0.30-0.81, p=0.005) and with lesser HCAIs with bacterial isolates (RR 0.33, CI95% 0.14-0.77, p=0.011). CONCLUSIONS: Copper adhesive plating combined with UV-C disinfection were associated with a drop in HCAI rates and with the elimination of ESBL-caused HCAIs. Hence, we propose that these strategies be considered in MDRO proliferation preventions.

[Wilson's disease: overview]. / Enfermedad de Wilson.

Wilson's disease (WD) is an uncommon hereditary disorder caused by a deficiency in the ATP7B transporter. The protein codified by this gene facilitates the incorporation of the copper into ceruloplasmin. Therefore, WD accumulates copper primary in the liver and secondary in other organs, such as the central nervous system. It represents a wide spectrum of disease, ranging from being asymptomatic in some patients to promote an acute liver failure in others. The diagnosis requires a combination of clinical signs and symptoms, as well as some diagnostic tests such as the measurement of serum ceruloplasmin, the urinary excretion of copper, the liver biopsy or the genetic testing. The treatment must be maintained lifelong and includes some drugs such as chelating agents (penicillamine and trientine) and inhibitors of the copper absorption (zinc salts). Lastly, the liver transplant should be an option for patients with end-stage liver disease.

[Cervical myelopathy due to copper deficiency secondary to dental zinc overload: A case report]. / Mielopatía cervical por déficit de cobre secundario a sobrecarga de zinc dental. A propósito de un caso.

We present the case of a 68-year-old man with progressive brachial and crural hypoaesthesia with gait ataxia suggesting subacute myelopathy of the posterior cords, demonstrated by MRI. After blood tests, a diagnosis of copper deficiency was made following zinc intoxication, secondary to the use of denture glue containing zinc. Treatment was started with copper and the dental glue was removed. Rehabilitation treatment was started with physiotherapy, hydrotherapy and occupational therapy. Functional improvement was achieved, going from an ASIAD level C4 to an ASIAD level C7 spinal cord injury. Copper levels should be studied in all non-compressive myelopathies of subacute onset if there is clear involvement of the posterior cords. Copper deficiency in analysis would establish the diagnosis. Rehabilitative treatment, supplementary copper supplementation and zinc withdrawal are essential to prevent irreversible neurological damage.

Social network analysis of biomedical research growth at a primarily undergraduate institution.

The National Institutes of Health Institutional Development Award Programs support the establishment and growth of biomedical research infrastructure in states that receive a low level of federal funding for biomedical research. The purpose of this investigation was to analyze the growth in research productivity over time. This program fostered an environment in which a biomedical research program could be developed and allowed to grow at Boise State University, a primarily undergraduate institution. The growth of the biomedical research community can be visualized through social network analysis.

Using bibliometrics to evaluate outcomes and influence of translational biomedical research centers.

Introduction: Federal grant funding to support infrastructure development of translational biomedical research centers is a form of public health intervention. Establishing rigorous methods for measuring center success and outcomes is essential to justify continued funding. Methods: Bibliometric data compiled from a 5-year funding cycle of neurodegeneration and translational neuroscience research center were analyzed using the package bibliometrix for open-source software R and the NIH-developed research tool iCite. Results: The research team and their collaborators (n = 485) produced 157 grant-citing publications from 2015-2020. The science was produced by small research teams clustered around three main communities of topics: Alzheimer's Disease, brain imaging, and neuropsychological testing in the elderly. Using the relative citation ratio, the publications produced by the research team were found to be influential when compared to other R01-funded publications. Conclusion: Recent developments in bibliometric analysis expand beyond traditional measurement capabilities to better understand the characteristics, outcomes, and influences of research teams. These findings can be used to inform researchers and institutions about research team composition, productivity, and success. Measures of research influence may be used to justify return on investment to funders.

COBRE for Skeletal Health and Repair: The Impact of Aging on the Capacity for Peripheral Nerve Regeneration.

Peripheral nerves are crucial to the motor and sensory function provided by our upper and lower extremities to our brain and spinal cord. Following trauma or illness, these nerves may be injured, leading to a loss of function that can be significantly debilitating. Fortunately, given the type of injury and under the right conditions, peripheral nerves can regenerate through well-coordinated biochemical processes. However, as individuals age, the ability for nerves to regenerate becomes less efficient, reducing nerve's potential for the nerve to return to its prior level of function. In this article, we review the research that has been conducted to illustrate the reasons for such a decline in regenerative capacity. In doing so, we explore the concept of inflammaging alongside aging-related impairments of the macrophage and Schwann cell during nerve regeneration.

Formative evaluation results of a phase 2 Center of Biomedical Research Excellence (COBRE).

INTRODUCTION: Because a primary focus of Centers of Biomedical Research Excellence (COBRE) is the development of junior-level investigators into competent and successful research scientists, evaluation of their skills, mentoring experiences, and usefulness of COBRE services is paramount to the transition of the Center to a self-sustaining, collaborative, multidisciplinary research environment. A formative evaluation, focused on the processes of a COBRE, was undertaken and is presented here. METHODS: Two instruments, one for completion by junior investigators and one for completion by mentors, were developed for the purpose of evaluating this COBRE. Areas of inquiry were relationships between junior investigators and mentors, research self-efficacy, mentee progress, and satisfaction with the COBRE. All eight of the COBRE's current junior investigators and six of their mentors completed the online questionnaires. RESULTS: Junior investigators were very positive about mentors and vice versa. Junior investigators were least positive about their progress as academicians and most positive about their abilities to develop collaborations with other scholars/professionals. Mentors felt as though junior investigators could benefit most by increasing the number of publications they had generated. CONCLUSIONS: Activities provided by the CardioPulmonary Vascular Biology (CPVB) COBRE were extremely positive. Junior investigators felt as though the scientific, academic, and professional development opportunities afforded by this COBRE were integral to their success as researchers; however they would like more assistance developing professional networks (i.e., serving on committees of professional societies). Leadership of the CPVB COBRE may consider expanding the role of their advisory committee to ensure these opportunities are provided.

[Black precipitate in parenteral nutrition]. / Precipitado negro en nutrición parenteral.

INTRODUCTION: Introduction: a black precipitate was observed in the filter during the infusion of a parenteral nutrition without lipids. There are similar findings published in which copper and sulphur (from cysteine) were found in the composition of the precipitate. Objective: to determine if copper and cysteine are involved in the formation of the precipitate. Methods: samples of the parenteral nutrition solution were taken before and after its passage through the filter. Amino acids concentrations were analysed in both samples by ion exchange chromatography and post-column derivatization with ninhydrin in a Biochrom 30 device. Copper concentrations were measured by atomic absorption spectrometry in a PerkinElmer AAnalyst™ 200 device. Results: a decrease in cysteine concentration of 29.3% was found. The concentration of copper decreased by 75.9%. Conclusions: the decrease in the concentrations of cysteine and copper in the filtered solution suggest that both are involved in the formation of the black precipitate observed in the filter.

INTRODUCCIÓN: Introducción: durante la infusión de una nutrición parenteral sin lípidos se observó un precipitado negro en el filtro. Hay hallazgos similares publicados en los que se han detectado cobre y azufre (proveniente de la cisteína) en la composición del precipitado. Objetivo: comprobar que la cisteína y el cobre intervienen en la formación del precipitado. Métodos: se tomaron muestras de la solución de nutrición parenteral antes y después de su paso por el filtro. Se analizaron en ambas muestras las concentraciones de aminoácidos mediante cromatografía de intercambio iónico y derivatización post-columna con ninhidrina en un equipo Biochrom 30 y las de cobre mediante espectrometría de absorción atómica en un equipo PerkinElmer AAnalyst™ 200. Resultados: las concentraciones de cisteína y cobre en la solución disminuyeron en un 29,3% y 75,9%, respectivamente. Conclusiones: la disminución de las concentraciones de cisteína y cobre en la solución filtrada sugieren que ambos están involucrados en la formación del precipitado negro observado en el filtro.

Influence of the type of amino acids in the formation of precipitates of copper and sulphur in parenteral nutrition.

INTRODUCTION: Objective: we found a black precipitate during the infusion of a parenteral nutrition without lipids. The objective of this study is to check the composition of the precipitate and the influence of the type of amino acids in its formation. Methods: four PN bags were prepared with the following composition: 1 l of amino acids solution, 150 g glucose, 60 mEq potassium, 217 mEq chloride, 105 mEq sodium, 15 mEq magnesium, 15 mEq calcium, 18.63 mmol phosphorus and trace elements (Addamel®). Each bag was prepared using a different type of amino acids solution with different amount of cysteine per litre: Tauramin® 10% (0.5 g/l), Primene® 10% (1.89 g/l), Tauramin® 12.6% (0.62 g/l) or Synthamin® 10% (0 g/l). Tauramin® 10% and Primene® 10% were packaged in glass containers whereas Tauramin® 12.6% and Synthamin® 10%, in plastic. The contents of each bag were filtered using Pall NEO96E 0.2 micron filters. A 2.25% area of each filter was observed by scanning electron microscopy at 100x magnification. The analysis by energy dispersive spectroscopy (EDS) was performed at 1,000x magnification. Results: in the Primene® 10% and Tauramin® 10% filters, a greater amount of precipitate was observed than with Tauramin® 12.6% and Synthamin® 10%. The percentage of copper and sulphur in each area of the filters studied was, respectively, 22.9% and 11.5% (Primene® 10%), 19.3% and 9.6% (Tauramin® 10%), 3.7% and 0% (Tauramin® 12.6%), 2.5% y 0% (Synthamin® 10%). Conclusions: the observed precipitate contains copper and sulphur. Precipitate formation occurs in high cysteine content amino acids solutions packaged in glass containers. It is important to use filters in the administration of PN to ensure that this type of precipitates are retained and do not pass to the patient. Key words.

INTRODUCCIÓN: Objetivo: durante la infusión de una nutrición parenteral (NP) sin lípidos se observó un precipitado negro en el filtro. El objetivo del estudio es comprobar la composición del precipitado y la influencia del tipo de aminoácidos en su formación. Métodos: se prepararon cuatro bolsas de NP con 1.000 ml de solución de aminoácidos, 150 g glucosa, 60 mEq potasio, 217 mEq cloruro, 105 mEq sodio, 15 mEq magnesio, 15 mEq calcio, 18,63 mmol fósforo y oligoelementos (Addamel®). Se utilizaron distintos tipos de aminoácidos con concentraciones de cisteína diferentes: Tauramin® 10% (0,5 g/l), Primene® 10% (1,89 g/l), Tauramin® 12,6% (0,62 g/l) o Synthamin® 17 (0 g/l). Tauramin® 10% y Primene® 10% estaban envasados en vidrio y Tauramin® 12,6% y Synthamin® 17, en plástico. El contenido de cada bolsa se filtró utilizando filtros Pall NEO96E de 0,2 micras. Se estudió un área de 2,25% de cada filtro mediante microscopía electrónica de barrido a 100 aumentos. El análisis mediante espectroscopia de dispersión de energía (EDS) se realizó a 1.000 aumentos. Resultados: en los filtros con Primene® 10% y Tauramin® 10%, se observó mayor precipitación que con Tauramin® 12,6% y Synthamin® 10%. El porcentaje de cobre y azufre en cada área de los filtros estudiados fue 22,9% y 11,5% (Primene® 10%), 19,3% y 9,6% (Tauramin® 10%), 3,7% y 0% (Tauramin 12,6%), 2,5% y 0% (Synthamin 10%). Conclusiones: el precipitado observado contiene cobre y azufre. La formación de precipitados se produce con soluciones de aminoácidos envasadas en vidrio, con gran cantidad de cisteína. Es importante usar filtros en la administración de NP para garantizar que los precipitados se retengan y no se pasen al paciente.

Studies on bioaccumulation patterns, biochemical and genotoxic effects of copper on freshwater fish, Catla catla: an in vivo analysis / Estudos sobre padrões de bioacumulação, efeitos bioquímicos e genotóxicos do cobre em peixes de água doce, Catla catla: uma análise in vivo

During present study, the copper (Cu) mediated oxidative stress was measured that induced DNA damage by concentrating in the tissues of fish, Catla catla (14.45±1.24g; 84.68±1.45mm) (Hamilton,1822). Fish fingerlings were retained in 5 groups for 14, 28, 42, 56, 70 and 84 days of the exposure period. They were treated with 2/3, 1/3, 1/4 and 1/5 (T1-T4) of 96h lethal concentration of copper. Controls were run along with all the treatments for the same durations. A significant (p < 0.05) dose and time dependent concentration of Cu was observed in the gills, liver, kidney, muscles, and brain of C. catla. Among organs, the liver showed a significantly higher concentration of Cu followed by gills, kidney, brain, and muscles. Copper accumulation in these organs caused a significant variation in the activities of enzymes viz. superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). The SOD activity varied significantly in response to the exposure time of Cu as 56 > 70 > 42 > 84 > 28 > 14 days while CAT activity exhibited an inverse relationship with the increase in Cu concentration. POD activity showed a significant rise with an increase in Cu exposure duration. Comet assay exhibited significant DNA damage in the peripheral erythrocytes of Cu exposed C. catla. Among four exposure concentrations, 2/3rd of LC50 (T1) caused significantly higher damage to the nuclei compared to control. Increased POD and SOD activity, as well as a decrease in CAT activity in response to Cu, demonstrates the involvement of a protective mechanism against reactive oxygen species (ROS), whereas increased ROS resulted in higher DNA damage. These above-mentioned molecular markers can be efficiently used for the biomonitoring of aquatic environments and conservation of edible fish fauna.

Durante o presente estudo, o estresse oxidativo mediado pelo cobre (Cu) foi medido que induziu danos ao DNA por concentração nos tecidos de peixes, Catla catla (14,45 ± 1,24g; 84,68 ± 1,45mm) (Hamilton, 1822). Os alevinos foram retidos em 5 grupos por 14, 28, 42, 56, 70 e 84 dias do período de exposição. Eles foram tratados com 2/3, 1/3, 1/4 e 1/5 (T1-T4) de 96h de concentração letal de cobre. Os controles foram executados junto com todos os tratamentos para as mesmas durações. Uma significativa (p <0,05) concentração dependente do tempo e da dose de Cu foi observada nas brânquias, fígado, rim, músculos e cérebro de C. catla. Entre os órgãos, o fígado apresentou uma concentração significativamente maior de cobre, seguido por guelras, rins, cérebro e músculos. O acúmulo de cobre nesses órgãos causou uma variação significativa nas atividades das enzimas viz. superóxido dismutase (SOD), catalase (CAT) e peroxidase (POD). A atividade de SOD variou significativamente em resposta ao tempo de exposição de Cu como 56> 70> 42> 84> 28> 14 dias, enquanto a atividade de CAT exibiu uma relação inversa com o aumento na concentração de Cu. A atividade POD mostrou um aumento significativo com um aumento na duração da exposição ao Cu. O ensaio do cometa exibiu dano significativo ao DNA induzido por Cu nos eritrócitos periféricos de C. catla. Entre as quatro concentrações de exposição, 2/3 do LC50 (T1) causou danos significativamente maiores aos núcleos em comparação com o controle. O aumento da atividade de POD e SOD, bem como uma diminuição na atividade de CAT em resposta ao Cu, demonstra o envolvimento de um mecanismo protetor contra espécies reativas de oxigênio (ROS), enquanto o aumento de ROS resultou em maior dano ao DNA. Esses marcadores moleculares mencionados acima podem ser usados ​​de forma eficiente para o biomonitoramento de ambientes aquáticos e conservação da ictiofauna comestível.

Studies on bioaccumulation patterns, biochemical and genotoxic effects of copper on freshwater fish, Catla catla: an in vivo analysis

Abstract During present study, the copper (Cu) mediated oxidative stress was measured that induced DNA damage by concentrating in the tissues of fish, Catla catla (14.45±1.24g; 84.68±1.45mm) (Hamilton,1822). Fish fingerlings were retained in 5 groups for 14, 28, 42, 56, 70 and 84 days of the exposure period. They were treated with 2/3, 1/3, 1/4 and 1/5 (T1-T4) of 96h lethal concentration of copper. Controls were run along with all the treatments for the same durations. A significant (p 0.05) dose and time dependent concentration of Cu was observed in the gills, liver, kidney, muscles, and brain of C. catla. Among organs, the liver showed a significantly higher concentration of Cu followed by gills, kidney, brain, and muscles. Copper accumulation in these organs caused a significant variation in the activities of enzymes viz. superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). The SOD activity varied significantly in response to the exposure time of Cu as 56 > 70 > 42 > 84 > 28 > 14 days while CAT activity exhibited an inverse relationship with the increase in Cu concentration. POD activity showed a significant rise with an increase in Cu exposure duration. Comet assay exhibited significant DNA damage in the peripheral erythrocytes of Cu exposed C. catla. Among four exposure concentrations, 2/3rd of LC50 (T1) caused significantly higher damage to the nuclei compared to control. Increased POD and SOD activity, as well as a decrease in CAT activity in response to Cu, demonstrates the involvement of a protective mechanism against reactive oxygen species (ROS), whereas increased ROS resulted in higher DNA damage. These above-mentioned molecular markers can be efficiently used for the biomonitoring of aquatic environments and conservation of edible fish fauna.

Resumo Durante o presente estudo, o estresse oxidativo mediado pelo cobre (Cu) foi medido que induziu danos ao DNA por concentração nos tecidos de peixes, Catla catla (14,45 ± 1,24g; 84,68 ± 1,45mm) (Hamilton, 1822). Os alevinos foram retidos em 5 grupos por 14, 28, 42, 56, 70 e 84 dias do período de exposição. Eles foram tratados com 2/3, 1/3, 1/4 e 1/5 (T1-T4) de 96h de concentração letal de cobre. Os controles foram executados junto com todos os tratamentos para as mesmas durações. Uma significativa (p 0,05) concentração dependente do tempo e da dose de Cu foi observada nas brânquias, fígado, rim, músculos e cérebro de C. catla. Entre os órgãos, o fígado apresentou uma concentração significativamente maior de cobre, seguido por guelras, rins, cérebro e músculos. O acúmulo de cobre nesses órgãos causou uma variação significativa nas atividades das enzimas viz. superóxido dismutase (SOD), catalase (CAT) e peroxidase (POD). A atividade de SOD variou significativamente em resposta ao tempo de exposição de Cu como 56> 70> 42> 84> 28> 14 dias, enquanto a atividade de CAT exibiu uma relação inversa com o aumento na concentração de Cu. A atividade POD mostrou um aumento significativo com um aumento na duração da exposição ao Cu. O ensaio do cometa exibiu dano significativo ao DNA induzido por Cu nos eritrócitos periféricos de C. catla. Entre as quatro concentrações de exposição, 2/3 do LC50 (T1) causou danos significativamente maiores aos núcleos em comparação com o controle. O aumento da atividade de POD e SOD, bem como uma diminuição na atividade de CAT em resposta ao Cu, demonstra o envolvimento de um mecanismo protetor contra espécies reativas de oxigênio (ROS), enquanto o aumento de ROS resultou em maior dano ao DNA. Esses marcadores moleculares mencionados acima podem ser usados de forma eficiente para o biomonitoramento de ambientes aquáticos e conservação da ictiofauna comestível.

Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases / Doença de Wilson: o desafio diagnóstico e resultados do tratamento em uma série de 262 casos

Abstract Background Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations. Objective To describe the diagnostic features and response to treatment in our cohort of WD patients. Methods This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, ATP7B genotyping, and response to treatment. Results Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the ATP7B gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (p= 0.2). Nine patients underwent liver transplantation and 82 died. Conclusion Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include ATP7B genotyping and therapeutic alternatives in clinical practice.

Resumo Antecedentes A doença de Wilson (DW) é um distúrbio autossômico recessivo caracterizado por acúmulo de cobre lesivo aos órgãos. O diagnóstico precoce é dificultado pela raridade e diversidade de apresentações. Objetivo Descrever características ao diagnóstico e resposta ao tratamento em uma coorte de DW. Métodos Análise retrospectiva de 262 casos de DW quanto à apresentação clínica, exames complementares, genotipagem e resposta ao tratamento. Resultados Os sintomas surgiram em uma média aos 17,4 (7-49) anos, e os pacientes foram acompanhados por uma média de 9,6 (0-45) anos. Os pacientes apresentaram principalmente formas hepáticas (36,3%), neurológicas (34,7%) e neuropsiquiátricas (8,3%). Outras apresentações foram hematológicas, renais e musculoesqueléticas. Apenas 16,8% eram assintomáticos. Anéis de Kayser-Fleischer ocorreram em 78,3% dos pacientes, hipoceruloplasminemia em 98,3%, e cuprúria elevada/24h em 73,0%, com aumento após D-penicilamina em 54,0%. Mutações do gene ATP7B foram detectadas em 84,4% dos alelos pesquisados. A ressonância magnética cerebral mostrou alterações em gânglios da base em 77,7% dos pacientes. O tratamento com D-penicilamina foi a escolha inicial em 93,6% dos 245 casos e foi trocado em 21,1% devido a efeitos adversos. Terapias de segunda linha foram zinco e trientina. A resposta terapêutica não diferiu significativamente entre os medicamentos (p= 0,2). Nove pacientes receberam transplante hepático e 82 faleceram. Conclusão O diagnóstico da DW ainda ocorre em estágios tardios, e as opções terapêuticas são limitadas. A DW deve ser considerada precocemente no diagnóstico diferencial de pessoas com menos de 40 anos com manifestações compatíveis. É necessário incorporar na prática clínica a genotipagem do ATP7B e alternativas terapêuticas à penicilamina.

Conhecimento, atitude e prática de médicos brasileiros sobre a inserção do DIU imediatamente após o parto e o abortamento / Knowledge, Attitudes, and Practices of Brazilian Physicians Regarding Intrauterine Device Insertion Immediately After Childbirth and Abortion

RESUMO Objetivo: Avaliar o conhecimento, a atitude e a prática dos mé- dicos brasileiros sobre a inserção do dispositivo intrauterino no pós-parto e pós-abortamento imediatos. Métodos: Estudo trans- versal envolvendo enquete de plantonistas de hospitais públicos brasileiros. Os participantes responderam a um questionário on- line anônimo com perguntas fechadas para avaliar seu conhe- cimento, atitude e experiência quanto à inserção de dispositivo intrauterino de cobre no pós-parto e pós-abortamento imedia- tos. Resultados: Cento e vinte e sete médicos que trabalham em 23 hospitais nas cinco regiões geográficas do Brasil responde- ram ao questionário. A maioria era do sexo feminino (68,5%) e trabalhava em hospitais universitários (95,3%). O escore médio (desvio-padrão) de conhecimento (escala de 0-10) foi de 5,3 (1,3); apenas 27,6% dos participantes tiveram escores ≥ 7,0. A maioria dos médicos (73,2%) colocaria o DIU pós-parto em si/familia- res. Cerca de 42% afirmaram não ter recebido nenhum treina- mento sobre inserção de dispositivo intrauterino pós-parto ou pós-abortamento. Nos últimos 12 meses, 19,7%, 22,8% e 53,5% dos respondentes afirmaram não ter inserido nenhum dispositi- vo intrauterino durante uma cesariana, imediatamente após um parto vaginal e um abortamento, respectivamente. Conclusão: A maioria das participantes do estudo tem atitude positiva em relação à inserção de dispositivos intrauterinos no pós-parto imediato, mas tem conhecimento limitado sobre o uso desse método contraceptivo. Grande porcentagem dos participantes não teve treinamento anterior sobre inserção de dispositivo in- trauterino pós-parto e pós-abortamento e não realizou nenhuma inserção nos últimos doze meses. São necessárias estratégias para melhorar o conhecimento, o treinamento e a experiência dos médicos brasileiros sobre a inserção de dispositivo intraute- rino no pós-parto e pós-abortamento imediatos.

Caracterización de consorcios microbianos lixiviantes de sulfuro de cobre aislados de drenajes ácidos de minas altoandinas

La biolixiviación, usando consorcios microbianos, es considera una alternativa ecoeficiente y de bajo costo para la recuperación de metales a partir de minerales de baja ley. En este estudio, se realizó la caracterización fisiológica y molecular de consorcios microbianos psicrotolerantes lixiviantes (CMPL), aislados de drenajes ácidos de minas de cuatro localidades mineras de las provincias de Pasco y Huarochirí, Perú, ubicados sobre los 4200 m de altitud. Se aislaron seis consorcios adaptados a medio 9K con ion ferroso y medio basal 9K con CuS al 0.5% p/v a 15 °C. Se evidenció la liberación de cobre en todos los consorcios. El CMPL con mejor crecimiento, presentó una recuperación de cobre de 12.47% en 30 días de evaluación. Los análisis de la secuenciación del gen ARNr 16S de la comunidad bacteriana, mostraron que los CMPL están dominados por el género Acidithiobacillus, seguido de Acidiphilium. En conclusión, se obtuvieron consorcios que pueden ser aplicados en biolixiviación de cobre en la minería altoandina.

Bioleaching, using microbial consortia, is regarded as an eco-efficient and cost-effective alternative for the recovery of metals from low-grade ores. In this study, we conducted physiological and molecular characterization of psychrotolerant leaching microbial consortia (PLMC) isolated from acid mine drainage in four mining sites within the Pasco and Huarochirí provinces of Peru, situated at altitudes above 4200 meters. Six consortia adapted to a medium containing ferrous ions (9K medium) and a basal medium with 0.5% w/v CuS at 15°C were isolated. All consortia exhibited copper release. The PLMC with the most robust growth achieved a copper recovery of 12.47% within 30 days of evaluation. 16S rRNA gene sequencing analysis of the bacterial community revealed that the PLMCs were predominantly dominated by the genus Acidithiobacillus, followed by Acidiphilium. In conclusion, consortia suitable for copper biolixiviation in high-altitude mining contexts were successfully obtained.