Development of clinical and laboratory biomarkers in an international cohort of 428 children with lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. METHODS: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. RESULTS: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. CONCLUSIONS: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission.

Colonic malakoplakia in a pediatric renal transplant recipient case report.

Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred after 9 months prompting the transition of therapy to oral gentamicin with subsequent remission. Malakoplakia should be considered in the differential of solid organ transplant recipients with recurrent gastrointestinal infections.

International cohort of 382 children with lupus nephritis - presentation, treatment and outcome at 24 months.

BACKGROUND: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. METHODS: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. RESULTS: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y-9y, 5m) (14y, 2m-18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. CONCLUSION: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Lupus Nephritis, Autoantibody Production and Kidney Outcomes in Males with Childhood-Onset Systemic Lupus Erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) only represents 20% of all SLE patients, and males with SLE only represent 10%. To study this rare SLE subset, males diagnosed with cSLE over a 30-year period were identified. Organ involvement, autoantibody production, hypocomplementemia, and kidney biopsy findings were compared to cSLE females. Outcomes were assessed using SLE Disease Activity Index scores, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and Childhood Arthritis and Rheumatology Research Alliance definitions for nephritis responsiveness. Of 95 males and 545 females with cSLE, 62% and 57% developed nephritis, respectively. Median age of cSLE onset was 14 years in both genders. Among males, 80% of non-Hispanic whites, 64% of blacks, 59% of Hispanics, and 50% of Asians developed nephritis. The prevalence of pure and mixed class V membranous nephritis was 33%. Median follow-up was 3.2 years (range 0.1-18). Complete kidney responses were seen in 70% after a median 24 months; however, relapse rates were 46%. Kidney disease flares were 56% nephritic and 44% proteinuric. Males and females with cSLE present with comparable rates and nephritis class. While overall and kidney response rates are favorable, kidney disease relapses are common among males.

Defining renal remission in an international cohort of 248 children and adolescents with lupus nephritis.

OBJECTIVE: We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. METHODS: Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.

Chemical characteristics and colorimetric properties of non-centrifugal cane sugar ("panela") obtained via different processing technologies.

Non-centrifugal cane sugar (NCS) samples obtained by traditional moulding and granulation, and also via a novel spray-drying powdering process without additives, were assessed to characterise their sugar and phenolic profiles, flavonoid content, as well as colour parameters. As expected, sucrose was the predominant sugar (91.9-95.5%), followed by glucose (2.9-4.6%), and fructose (1.6-3.7%). Total phenolic content was between 0.4 and 0.6% and total flavonoid content into the range of 0.2-0.4%. Six phenolic acids were found in all NCS samples: protocatechuic acid (0.36-0.94 µg/100 g), vanillic acid (0.70-1.45 µg/100 g), chlorogenic acid (2.08-3.82 µg/100 g), syringic acid (1.08-2.80 µg/100 g), p-coumaric acid (0.69-1.35 µg/100 g), and ferulic acid (0.50-0.95 µg/100 g). The thermal treatment under high temperatures required in the production of granulated products was related with darker colours and changes in phenol and flavonoid contents. In contrast, spray drying generates clearer products, but with slightly less phenol and flavonoid contents.

Green chemicals from used cooking oils: Trends, challenges, and opportunities.

Food waste reduction is fundamental for sustainable development and pursuing this goal, recycling and the valorization of used cooking oil (UCO) can play a major contribution. Although it has been traditionally used for biofuel production, the oleochemical potential of UCOs is vast. UCOs can be used as feedstock for a large variety of value-added green chemicals including plasticizers, binders, epoxides, surfactants, lubricants, polymers, biomaterials, and different building blocks. Thus, UCO transformation into functional chemicals can bring long-term stability to the supply chain, avoiding the current dependence on commodity products. In this regard, this work describes some of the potential benefits of using UCOs as feedstock in oleochemical biorefineries. In addition, some of the most recent investigations on the valorization of UCOs other than biofuel are presented. Finally, major challenges and future directions are discussed.

Polimorfismos del gen del receptor para la hormona luteinizante (LHR - LHGCR) en folículos ováricos de vacas Romosinuano y Brahman ciclando / Luteinizing hormone choriogonadotropin receptor (LHGCR) gene polymorphism in ovarian follicles from cycling Romosinuano and Brahman cows / Polimorfismos do gene receptor para o hormônio luteinizante (LHR - LHGCR) em folículos ováricos de vacas Romosinuano e Brahman no ciclo

Resumen El gen del receptor para la hormona luteinizante (LHR-LHCGR) es un gen altamente conservado y su mRNA origina diferentes variantes por corte y empalme alternativo (splicing alternativo). En bovinos se han reportado variantes que traducen en proteína pero ésta no atraviesa la membrana celular; en humanos ante una deleción del exón 10 no hay respuesta a la acción de la LH, por lo tanto, es razonable asumir que las diferencias en la respuesta a la LH estén relacionadas con la expresión de los LHR. El objetivo de este trabajo fue comparar entre la raza criolla Colombiana Romosinuano y la raza Brahman los posibles polimorfismos del ARNm del gen como potenciales indicadores de fertilidad. Se tomaron 5 vacas ciclando de cada raza se extirpó el ovario que contenía un folículo preovulatorio, se retiró la pared folicular, se extrajo el RNA total y se sintetizó, amplificó, secuenció y comparó el ADNc contra secuencias ya reportadas, presentando una alta similitud. Se concluye que en estas razas la ausencia de variantes en la expresión del gen, estaría asociada a buen desempeño reproductivo.

Abstract The luteinizing hormone (LH) choriogonadotropin receptor (LHCGR) gene is highly conserved and its mRNA causes variants by alternative splicing. Variants have been reported in cattle that translate into protein; however, this does not cross the cell membrane. Exon 10 deletion in humans does not trigger a response to the action of LH; it is therefore reasonable to assume that differences regarding response to LH are related to LHR expression. This work was aimed at comparing the Colombian creole Romosinuano breed to the Brahman breed regarding possible HCGR gene mRNA polymorphisms as potential fertility indicators. Five cycling cows were taken from each breed and the ovaries containing pre-ovulatory follicles were excised, the follicular wall was removed and total RNA extracted. The cDNA was synthesised, amplified, sequenced and compared to already reported sequences, great similarity being observed. It was concluded that the lack of variants regarding gene expression in these breeds would be associated with good reproductive performance.

Resumo O gene do receptor para o hormônio luteinizante (LHR-LHCGR) é altamente conservado e seu mRNA origina diferentes variantes por splicing alternativo. Em bovinos, foram registradas variantes que se traduzem em proteína, mas esta não atravessa a membrana celular; em humanos quando há uma deleção do exon 10 não há nenhuma resposta à ação do LH, portanto, é possível que as diferenças na resposta ao LH estão relacionados à expressão do LHR. O objetivo deste estudo foi comparar os polimorfismos do mRNA do gene entre a raça crioula colombiana Romosinuano e a raça Brahman, como potenciais indicadores de fertilidade. Foram avaliadas cinco fêmeas de cada raça, retirou-se o ovário que continha um folículo pré-ovulatório, retirou-se a parede folicular, o RNA total foi extraído. Se sintetizou, amplificou, sequenciou e comparou o cDNA com sequencias já descritas, a qual presentou alta semelhança.

Used cooking oils as potential oleochemical feedstock for urban biorefineries - Study case in Bogota, Colombia.

This work is focused on assessing the potential for the exploitation of used cooking oils (UCOs) as oleochemical feedstock for urban biorefineries. The study case was developed for the city of Bogotá, Colombia. Initially, and according to data from major fats and oils distributors, market information, and public databases, it was estimated that total annual generation of UCOs in Colombia is about 225,000 t, with a per capita of ca. 5 kg/person/yr. Correspondingly, UCOs generation in Bogotá was estimated in at least 45,000 t/yr., with a major generation occurring at Household and HORECA (Hotels, Restaurants and Catering) segments. Specifically in HORECA, fast food restaurants (in particular those of hamburger and chicken) were identified as the main UCOs generators with a suitable supply for industrial exploitation. Then, UCOs samples from this segment of restaurants were subjected to physicochemical characterization by determination of density, volatile matter content, acid value, color, peroxide value, saponification value, iodine value, and content of total polar compounds. The properties associated with the degree of degradation of the oil showed a large variation, even among samples from the same origin. This heterogeneity indicates the need for a pre-treatment process before its reuse. Despite the heterogeneity of the samples, density, iodine value, and saponification value showed slight changes among the different restaurants, largely depending on the nature of the processed cooking oil rather than on the cooking conditions. The collected UCOs showed iodine values and saponification indexes ranging between 80 and 119 g I2/100 g, and 178-201 mg KOH/g, respectively. This indicates that after a suitable purification, UCOs could be used as raw material for a variety of high value oleochemicals. Finally, based upon market data, and to boost further studies, some promissory value-added derivatives are identified.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial.

BACKGROUND AND OBJECTIVES: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS: The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS: ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

Physicochemical and sensory (aroma and colour) characterisation of a non-centrifugal cane sugar ("panela") beverage.

Non-centrifugal cane sugar (NCS), also called "panela", is a high carbohydrate-content food obtained by boil evaporation of the sugar cane juice. This study was undertaken to assess physicochemical properties and sensory characteristics of panela beverage at two different concentrations. Evaluation of pH, °Brix, and colour (tristimulus colorimetry) was carried out in all panela drink samples. In order to characterise the odour-active volatiles of the beverage, a simultaneous steam distillation-solvent extraction method was applied using a mixture of diethyl ether-pentane (1:1,w/w) as solvent. The Aroma Extract Dilution Analysis revealed the presence of six odour-active compounds, being 2-methyl pyrazine the key aroma compound of this beverage. PCA (Principal Component Analysis) showed that there were no differences in the aroma and physicochemical properties (pH and °Brix) with respect to the geographical origin of analysed samples; however colour depends on heating during processing of NCS.

High titer anti-basement membrane antibodies in a subset of patients with pediatric systemic lupus erythematosus.

BACKGROUND/AIMS: There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis. METHODS: Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE. RESULTS: MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients. CONCLUSION: The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.

A novel process for recovery of fermentation-derived succinic acid: process design and economic analysis.

Recovery and purification of organic acids produced in fermentation constitutes a significant fraction of total production cost. In this paper, the design and economic analysis of a process to recover succinic acid (SA) via dissolution and acidification of succinate salts in ethanol, followed by reactive distillation to form succinate esters, is presented. Process simulation was performed for a range of plant capacities (13-55 million kg/yr SA) and SA fermentation titers (50-100 kg/m(3)). Economics were evaluated for a recovery system installed within an existing fermentation facility producing succinate salts at a cost of $0.66/kg SA. For a SA processing capacity of 54.9 million kg/yr and a titer of 100 kg/m(3) SA, the model predicts a capital investment of $75 million and a net processing cost of $1.85 per kg SA. Required selling price of diethyl succinate for a 30% annual return on investment is $1.57 per kg.

Remoción de níqeel presente en aguas efluentes ndustriales mediante utilizacióón de sustratos de aserrín de pino / Removal of nickll from industrial waste water using pine sawdust / Eliminação de nqquel de águas residuais industriais usando serragem do pinheiro

Se evaluaron dos variedades de aserrín de pino (Pinus cupresus, Pinus caribeae) para la remoción de Ni2+ presente en efluentes industriales. Un estudio comparativo a través de operaciones batch permitió establecer la influencia de la concentración inicial del metal, la relación adsorbente a efluente y la velocidad de agitación en el proceso de remoción. La variedad Pinus cupresus arrojó la mayor adsorción, 0,53 mgNi/g, y esto, sumado a su fácil adquisición y bajo costo, lo hacen un adsorbente con gran potencial. Se ajustó un modelo cinético para la adsorción del metal y de modo paralelo se demostró que el fenómeno se da principalmente por intercambio iónico con Ca2+ y Mg2+ presentes en el aserrín. La torta húmeda residual puede disponerse por incineración ya que aproximadamente el 44% del níquel queda depositado en las cenizas. Finalmente se implementó una columna de adsorción piloto y se alcanzó una eficiencia de remoción del 57%.

Sawdust of two varieties of pine (Pinus cupresus, Pinus caribeae) have been studied for the removal Ni2+ from industrial wastes. A comparative study using batch operations allowed establishing the influence of initial metal concentration, amount of adsorbent and stirring rate in the removal process. Pinus cupresus variety shows the biggest adsorption, 0,53 mgNi/g; and considering its availability and low cost, it becomes a potential commercial adsorbent. A kinetic model was fitted for the metal adsorption. The experimental results provided evidence for ionic exchange with Ca2+ and Mg2+ as the major adsorption mechanism. The residual wet cake can be disposed by incineration, because about 44% of nickel is deposited in the ashes. Finally an adsorption column was developed achieving an efficiency of 57% in the removing process.

Duas variedades da serragem de pinheiro (Pinus cupresus, Pinus caribeae) foram investigadas para a remoção de Ni2+ de resíduos industriais.Umestudo comparativo usando operações de lote permitiu estabelecer a influência da concentração metálica inicial, a quantidade de adsorvente e a velocidade de agitação no processo de eliminaçao. A variedade Pinus cupresus mostra a adsorção maior, 0,53 mgNi/g. Considerando a sua disponibilidade e baixo preço, ele vira um adsorvente comercial potencial. Um modelo cinético foi ajustado para a adsorção metálica. Os resultados experimentais forneceram evidência da troca iônica com principalmente Ca2+eMg2+ como o mecanismo de adsorção principal. O bolo úmido residual pode ser disposto pela incineração, porque aproximadamente 44% de níquel é depositado nas cinzas. Finalmente, uma coluna de adsorção foi desenvolvida logrando uma eficiência de 57% no processo de remoção.