Técnica de Latarjet para la inestabilidad anterior de hombro: implicaciones en la inervación del músculo subescapular / Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle

Introducción: El objetivo de este estudio es analizar la relación existente entre la inervación del músculo subescapular y los pasos quirúrgicos de la técnica de Latarjet. Material y método: Se realizó un estudio anatómico mediante disección de 12 hombros fijados en formol, y se analizó el patrón de inervación del músculo subescapular. Se midió el tamaño del tendón en la interlínea articular, la distancia craneocaudal desde el borde superior al borde inferior del subescapular, en la entrada de los nervios, y la distancia mediolateral, desde los nervios hasta la interlínea articular. Se realizó la técnica de Latarjet y se midieron las distancias horizontales de los nervios subescapulares a la interlínea articular y de los nervios a la división del subescapular. Se describió la zona de seguridad por la que transcurre la división del subescapular sin dañar los nervios. Resultados: El músculo subescapular está inervado por 3 ramas del nervio subescapular: superior, medio e inferior, que siguen una distribución constante. No se encontraron diferencias estadísticamente significativas en las distancias de los nervios medidas antes y después de la técnica de Latarjet. Para evitar lesionar los nervios, es preciso realizar la división del subescapular entre los dos tercios superiores y el tercio inferior a lo largo del músculo. Conclusión: El músculo subescapular presenta una triple inervación constante. No hemos apreciado cambios estadísticamente significativos en la inervación tras la cirugía de Latarjet. Por tanto, la técnica de Latarjet parece respetar esta inervación al realizar la división del subescapular en su zona de seguridad.

Introduction: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. Materials and methods: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. Results: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds’ proportions throughout all the split must be maintained. Conclusions: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.(AU)

[Translated article] Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle / Técnica de Latarjet para la inestabilidad anterior de hombro: implicaciones en la inervación del músculo subescapular

Introducción: El objetivo de este estudio es analizar la relación existente entre la inervación del músculo subescapular y los pasos quirúrgicos de la técnica de Latarjet. Material y método: Se realizó un estudio anatómico mediante disección de 12 hombros fijados en formol, y se analizó el patrón de inervación del músculo subescapular. Se midió el tamaño del tendón en la interlínea articular, la distancia craneocaudal desde el borde superior al borde inferior del subescapular, en la entrada de los nervios, y la distancia mediolateral, desde los nervios hasta la interlínea articular. Se realizó la técnica de Latarjet y se midieron las distancias horizontales de los nervios subescapulares a la interlínea articular y de los nervios a la división del subescapular. Se describió la zona de seguridad por la que transcurre la división del subescapular sin dañar los nervios. Resultados: El músculo subescapular está inervado por 3 ramas del nervio subescapular: superior, medio e inferior, que siguen una distribución constante. No se encontraron diferencias estadísticamente significativas en las distancias de los nervios medidas antes y después de la técnica de Latarjet. Para evitar lesionar los nervios, es preciso realizar la división del subescapular entre los dos tercios superiores y el tercio inferior a lo largo del músculo. Conclusión: El músculo subescapular presenta una triple inervación constante. No hemos apreciado cambios estadísticamente significativos en la inervación tras la cirugía de Latarjet. Por tanto, la técnica de Latarjet parece respetar esta inervación al realizar la división del subescapular en su zona de seguridad.

Introduction: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. Materials and methods: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. Results: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds’ proportions throughout all the split must be maintained. Conclusions: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.(AU)

[Translated article] Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle.

INTRODUCTION: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. MATERIALS AND METHODS: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. RESULTS: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds' proportions throughout all the split must be maintained. CONCLUSIONS: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.

Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle. / Técnica de Latarjet para la inestabilidad anterior de hombro: implicaciones en la inervación del músculo subescapular.

INTRODUCTION: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. MATERIALS AND METHODS: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. RESULTS: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds' proportions throughout all the split must be maintained. CONCLUSIONS: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.

Approach for delabeling beta-lactam allergy in children.

A considerable number of pediatric patients treated with beta-lactam (BL) antibiotics develop delayed onset of skin rashes during the course of treatment. Although the most frequent cause of these symptoms is infectious, many cases are labeled as allergic reactions to these drugs. BL allergy labels could have a negative impact, as they imply avoidance of this group of drugs and the use of second-line antibiotics, leading to a potential increase in adverse effects and the utilization of less effective therapies. This constitutes a major public health concern and economic burden, as the use of broad-spectrum antibiotics can result in multidrug-resistant organisms and prolonged hospital stays. Therefore, it is crucial to delabel patients during childhood to avoid false labeling in adult life. Although the label of BL allergy is among the most frequent causes of allergy referral, its management remains controversial, and new diagnostic perspectives are changing the paradigm of managing BL allergies in children. Traditionally, drug provocation testing (DPT) was exclusively performed in patients who had previously obtained negative results from skin tests (STs). However, the sensitivity of STs is low, and the role of in vitro testing in the pediatric population is not well defined. Recent studies have demonstrated the safety of direct DPT without prior ST or serum tests for pediatric patients who report a low-risk reaction to BLs, which is cost-effective. However, there is still a debate on the optimal allergic workup to be performed in children with a benign immediate reaction and the management of children with severe cutaneous adverse drug reactions. In this review, we will discuss the impact of the label of BL allergy and the role of the different tools currently available to efficiently address BL allergy delabeling in children.

Attitudes scale toward cancer-related cognitive changes - an initial Colombian validation.

OBJECTIVE: The aim of this study was to develop an initial valid tool to measure attitudes toward cancer-related cognitive changes. SUBJECTS AND METHODS: After revising the literature, three main dimensions were hypothesized. Eight judges were contacted to obtain content validity evidence. A robust Exploratory Factor Analysis (EFA) was performed via a parallel analysis with an Unweighted Least Squares (ULS) estimator and polychoric correlations. The results were crossed with sociodemographic variables to find possible statistical differences and estimate the size effect. Analysis was performed in the software Factor and the statistical package R. RESULTS: A sample of 374 participants was obtained, involving oncology patients, their caregivers, and people from the general community. A statistical fit was found in two dimensions: Awareness and Judgments [root mean squared error of approximation (RMSEA) = 0.042, standardized root mean square residual (SRMR) = 0.02, comparative fit index (CFI) = 0.99, Tucker-Lewis index (TLI) = 0.98] with a moderate correlation between them (r = 0.612). Optimal reliability indices were obtained for the total scale and its dimensions. No real statistical difference was found between sociodemographic variables; the interpretation norms were established via the quartiles. CONCLUSIONS: The first attempt to measure the construct of interest was developed with two primary validity evidence based on the content and its internal structure. This instrument could help strengthen the prevention of cancer-related cognitive changes. More research is needed to adhere more valid evidence to the scale.

A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Corrigendum: Approach for delabeling beta-lactam allergy in children.

[This corrects the article DOI: 10.3389/falgy.2023.1298335.].

[Inveterate dislocation of the first metatarsophalangeal joint]. / Luxación inveterada de la primera metatarsofalángica.

Injuries in the metatarsophalangeal joint complex of the hallux are seen with greater frequency in athletes, their importance lies in the functional limitation it generates. Early diagnosis and treatment can reduce the sequelae, however, the recognition of chronic lesions and with it the implementation of adequate therapeutic management generate improvements in quality of life. This document records a case of inveterate dislocation of the metatarsophalangeal joint of the hallux of more than one year of evolution with involvement of the intersesamoid ligament which was corrected with arthrodesis achieving immediate satisfactory results, in the medium and long term with the subsequent functional recovery and total reduction of pain.

Las lesiones en el complejo articular metatarsofalángico del hallux son vistas con mayor frecuencia en deportistas, su importancia radica en la limitación funcional que genera. El diagnóstico y tratamiento temprano puede disminuir las secuelas; sin embargo, el reconocimiento de lesiones crónicas y con ello la implementación del adecuado manejo terapéutico, generan mejoras en la calidad de vida. Se registra en este documento un caso de luxación inveterada de la articulación metatarsofalángica del hallux de más de un año de evolución con compromiso del ligamento intersesamoideo, la cual fue corregida con artrodesis, se lograron resultados satisfactorios inmediatos, a mediano y largo plazo con la posterior recuperación funcional y disminución total del dolor.

Effects of substrate stress and light intensity on enhanced biological phosphorus removal in a photo-activated sludge system.

Photo-activated sludge (PAS) systems are an emerging wastewater treatment technology where microalgae provide oxygen to bacteria without the need for external aeration. There is limited knowledge on the optimal conditions for enhanced biological phosphorus removal (EBPR) in systems containing a mixture of polyphosphate accumulating organisms (PAOs) and microalgae. This research aimed to study the effects of substrate composition and light intensity on the performance of a laboratory-scale EBPR-PAS system. Initially, a model-based design was developed to study the effect of organic carbon (COD), inorganic carbon (HCO3) and ammonium-nitrogen (NH4-N) in nitrification deprived conditions on phosphorus (P) removal. Based on the mathematical model, two different synthetic wastewater compositions (COD:HCO3:NH4-N: 10:20:1 and 10:10:4) were examined at a light intensity of 350 µmol m-2 sec-1. Add to this, the performance of the system was also investigated at light intensities: 87.5, 175, and 262.5 µmol m-2 sec-1 for short terms. Results showed that wastewater having a high level of HCO3 and low level of NH4-N (ratio of 10:20:1) favored only microalgal growth, and had poor P removal due to a shortage of NH4-N for PAOs growth. However, lowering the HCO3 level and increasing the NH4-N level (ratio of 10:10:4) balanced PAOs and microalgae symbiosis, and had a positive influence on P removal. Under this mode of operation, the system was able to operate without external aeration and achieved a net P removal of 10.33 ±1.45 mg L-1 at an influent COD of 100 mg L-1. No significant variation was observed in the reactor performance for different light intensities, indicating the EBPR-PAS system can be operated at low light intensities with a positive influence on P removal.

Allergen Immunotherapy for Local Respiratory Allergy.

PURPOSE OF REVIESW: Local respiratory allergy (LRA) is an eosinophilic phenotype of chronic airway disease. Three entities have been described within the LRA spectrum: local allergic rhinitis (LAR) and local allergic asthma (LAA) in non-atopic patients, and dual allergic rhinitis (DAR) in atopic patients (coexistence of LAR and allergic rhinitis). In this article, we aim to review the current evidence on the therapeutic options for LRA. RECENT FINDINGS: No controlled study has assessed the effect of standard therapy (oral antihistamines, intranasal or inhaled corticosteroids, bronchodilators) in LRA subjects. Three randomized clinical trials and one observational study demonstrated that allergen immunotherapy (AIT) is able to control nasal and ocular symptoms, decrease the need for rescue medication, and improve quality of life in LAR individuals. Nasal or inhaled steroids can be expected to improve eosinophilic inflammation in LRA patients but cannot change the natural course of the disease. Moreover, the long-term and disease-modifying effects of AIT in LRA subjects need to be investigated.

Myriapod haemocyanin: the first three-dimensional reconstruction of Scolopendra subspinipes and preliminary structural analysis of S. viridicornis.

Haemocyanins (Hcs) are copper-containing, respiratory proteins that occur in the haemolymph of many arthropod species. Here, we report the presence of Hcs in the chilopode Myriapoda, demonstrating that these proteins are more widespread among the Arthropoda than previously thought. The analysis of transcriptome of S. subspinipes subpinipes reveals the presence of two distinct subunits of Hc, where the signal peptide is present, and six of prophenoloxidase (PPO), where the signal peptide is absent, in the 75 kDa range. Size exclusion chromatography profiles indicate different quaternary organization for Hc of both species, which was corroborated by TEM analysis: S. viridicornis Hc is a 6 × 6-mer and S. subspinipes Hc is a 3 × 6-mer, which resembles the half-structure of the 6 × 6-mer but also includes the presence of phenoloxidases, since the 1 × 6-mer quaternary organization is commonly associated with hexamers of PPO. Studies with Chelicerata showed that PPO activity are exclusively associated with the Hcs. This study indicates that Scolopendra may have different proteins playing oxygen transport (Hc) and PO function, both following the hexameric oligomerization observed in Hcs.

Myriapod haemocyanin: the first three-dimensional reconstruction of Scolopendra subspinipes and preliminary structural analysis of S. viridicornis

Haemocyanins (Hcs) are copper-containing, respiratory proteins that occur in the haemolymph of many arthropod species. Here, we report the presence of Hcs in the chilopode Myriapoda, demonstrating that these proteins are more widespread among the Arthropoda than previously thought. The analysis of transcriptome of S. subspinipes subpinipes reveals the presence of two distinct subunits of Hc, where the signal peptide is present, and six of prophenoloxidase (PPO), where the signal peptide is absent, in the 75 kDa range. Size exclusion chromatography profiles indicate different quaternary organization for Hc of both species, which was corroborated by TEM analysis: S. viridicornis Hc is a 6 × 6-mer and S. subspinipes Hc is a 3 × 6-mer, which resembles the half-structure of the 6 × 6-mer but also includes the presence of phenoloxidases, since the 1 × 6-mer quaternary organization is commonly associated with hexamers of PPO. Studies with Chelicerata showed that PPO activity are exclusively associated with the Hcs. This study indicates that Scolopendra may have different proteins playing oxygen transport (Hc) and PO function, both following the hexameric oligomerization observed in Hcs.

Myriapod haemocyanin: the first three-dimensional reconstruction of Scolopendra subspinipes and preliminary structural analysis of S. viridicornis

Haemocyanins (Hcs) are copper-containing, respiratory proteins that occur in the haemolymph of many arthropod species. Here, we report the presence of Hcs in the chilopode Myriapoda, demonstrating that these proteins are more widespread among the Arthropoda than previously thought. The analysis of transcriptome of S. subspinipes subpinipes reveals the presence of two distinct subunits of Hc, where the signal peptide is present, and six of prophenoloxidase (PPO), where the signal peptide is absent, in the 75 kDa range. Size exclusion chromatography profiles indicate different quaternary organization for Hc of both species, which was corroborated by TEM analysis: S. viridicornis Hc is a 6 × 6-mer and S. subspinipes Hc is a 3 × 6-mer, which resembles the half-structure of the 6 × 6-mer but also includes the presence of phenoloxidases, since the 1 × 6-mer quaternary organization is commonly associated with hexamers of PPO. Studies with Chelicerata showed that PPO activity are exclusively associated with the Hcs. This study indicates that Scolopendra may have different proteins playing oxygen transport (Hc) and PO function, both following the hexameric oligomerization observed in Hcs.

The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment.

BACKGROUND: Actinic keratosis (AK) may show extension down follicles, not only in cases with full-thickness epidermal atypia ('bowenoid' AK), but also in cases with atypia limited to the epidermal basalis. Previous studies have demonstrated that, in bowenoid AK, follicular extension is usually superficial, being limited to the upper follicular segment. Little is known about the depth of follicular involvement in cases of invasive squamous cell carcinoma of the skin (iSCC) arising from AK and the role of the follicle in iSCC pathogenesis. OBJECTIVE: This study investigated the relationship between follicular extension of atypical keratinocytes in an AK and the development of iSCC from the follicular wall. The depth of follicular extension was correlated with the depth invasion of iSCC. Differences between the differentiated and classical pathways of iSCC were also examined. METHODS: We performed a retrospective histologic review of 193 biopsy specimens of iSCC with an associated AK. We assessed the presence and depth of follicular extension of atypical keratinocytes in the AK, using tumour (Breslow) thickness and the follicular unit level (infundibular, isthmic and subisthmic), as well as iSCC being present directly adjacent to the follicular basalis. RESULTS: Follicular extension was present in 25.9% of the cases (50 cases), usually extending into the lower follicular segment. The iSCC was present directly adjacent to the follicular basalis in 58% of the cases (29 cases), correlating highly with the depth of follicular extension (infundibular: 3/12; isthmic: 21/33; subisthmic 5/5). CONCLUSION: The depth of follicular extension of atypical keratinocytes in an AK correlates with the development of depth of invasion of an associated iSCC, irrespective of the pathway of origin. It is therefore important to note the presence and the depth of follicular extension when diagnosing an AK, as follicular extension likely accounts for a significant proportion of recurrent AK and the development of iSCC following superficial treatment modalities.

Comparison of the inflammatory and stress response between sprint interval swimming and running.

The aim of the study was to compare myocellular damage, metabolic stress, and inflammatory responses as well as circulating sodium (Na+ ) and potassium (K+ ) between a single sprint swimming and running training. Eighteen subjects regularly involved in swimming and running training for at least 2 years were recruited. The subjects performed 8 × 30 seconds "all out" exercise on different days either by running or by swimming in a random order. Blood was collected before each training session, after the cessation of exercise (post) and after 2 hours of rest (2 hours). We then analyzed tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), interleukin 6 (IL-6), cortisol, creatine kinase MB isoform (CK-MB), lactate dehydrogenase (LDH), K+ , and Na+ . Neither TNF-α nor IL-10 differed between swimming and running. Most of the subjects showed a non-statistically significant increase of LDH and CK-MB after swimming. On the other hand, IL-6 (P < .05) and cortisol (P < .05) were significantly lower after 2 hours of swimming than after running. In addition, post-exercise K+ was significantly lower (P < .001) for swimming than for running. Our results provide evidence of similar inflammatory responses between exercise modes but lower metabolic stress in response to swimming than in response to running.

Epithelial-to-mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway, whereas proliferation plays a more significant role in the classical pathway.

BACKGROUND: Every actinic keratosis (AK) starts with atypia at the basal layers of the epidermis (AK I). Progression into invasive squamous cell carcinoma (iSCC) may occur following two main pathways, classical and differentiated. In the former, iSCC only occurs after involvement of the upper epidermal layers by atypical cells (AK III), while in the latter iSCC develops directly from AK I. In the anogenital mucosa, these two pathways are associated with differential expression of p53 and p16. OBJECTIVE: To explore differences between both pathways in the pathogenesis of AK, focusing on Ki67, p53, p16 and molecules that reveal epithelial-mesenchymal transition (EMT). METHODS: Tissue microarrays representative of superficial and deep portions of 80 consecutive iSCCs (53 DP/27CP) were studied immunohistochemically using antibodies against Ki67, p53, p16, vimentin, E-cadherin, ß-catenin and D2-40. The evaluation was performed by three researchers and the results compared to consensus. RESULTS: Invasive squamous cell carcinomas originated through the differentiated pathway exhibited significantly lower proliferative activity (Ki67) (30% vs 46%, P = 0.003) and significantly lower expression of vimentin (P < 0.001), E-cadherin (P < 0.001) and membranous ß-catenin (P < 0.001) than iSCCs developed through the classical pathway. The expression of E-cadherin and membranous ß-catenin was significantly correlated (Pearson's r = 0.386, Spearman's Rho < 0.001). There were no significant differences regarding the expressions of p53, p16 and D2-40. CONCLUSION: Epithelial-mesenchymal transition participates in transformation from AK I into iSCC (differentiated pathway), whereas a higher proliferative capacity facilitates intraepidermal extension in the classical pathway. Podoplanin, which is also involved in tumour invasion, does not seem to play a differential role in either pathway. Finally, the absence of differences in p53 and p16 expressions is at variance with other epithelia where the classical pathway is associated with human papillomavirus infection and can be explained by the fact that both AK pathways share identical mechanisms of actinic oncogenesis.

Nitrification by microalgal-bacterial consortia for ammonium removal in flat panel sequencing batch photo-bioreactors.

Ammonium removal from artificial wastewater by microalgal-bacterial consortia in a flat-panel reactor (FPR1) was compared with a microalgae-only flat-panel reactor (FPR2). The microalgal-bacterial consortia removed ammonium at higher rates (100±18mgNH4+-NL-1d-1) than the microalgae (44±16mgNH4+-NL-1d-1), after the system achieved a stable performance at a 2days hydraulic retention time. Nitrifiers present in the microalgae-bacteria consortia increased the ammonium removal: the ammonium removal rate by nitrifiers and by algae in FPR1 was, respectively, 50(±18) and 49(±22)mgNH4+-NL-1d-1. Apparently ammonium removal by algae was not significantly different between FPR1 and FPR2. The activity of the nitrifiers did not negatively affect the nitrogen uptake by algae, but improved the total ammonium removal rate of FPR1.

Diagnostic potential of NETosis-derived products for disease activity, atherosclerosis and therapeutic effectiveness in Rheumatoid Arthritis patients.

OBJECTIVES: 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). METHODS: One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker. Inflammatory and oxidative stress mediators were quantified in plasma and neutrophils. Two additional cohorts of 75 RA patients, treated either with Infliximab (n = 55) or Tocilizumab (n = 20) for six months, were evaluated. RESULTS: NETosis was found increased in RA patients, beside myeloperoxidase and neutrophil elastase protein levels. Cell-free nucleosomes plasma levels were elevated, and strongly correlated with the activity of the disease and the positivity for autoantibodies, alongside inflammatory and oxidative profiles in plasma and neutrophils. Moreover, ROC analyses showed that cell-free nucleosomes levels could identify RA patients showing early atherosclerosis with high specificity. RA patients treated either with IFX or TCZ for six months exhibited decreased generation of NETs. Concomitantly, clinical parameters and serum markers of inflammation were found reduced. Mechanistic in vitro analyses showed that inhibition of NETs extrusion by either DNase, IFX or TCZ, further abridged the endothelial dysfunction and the activation of immune cells, thus influencing the global activity of the vascular system. CONCLUSIONS: NETosis-derived products may have diagnostic potential for disease activity and atherosclerosis, as well as for the assessment of therapeutic effectiveness in RA.