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.

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.

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.

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.

The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid.

Betalactam (BL) antibiotics are the drugs most frequently involved in IgE-mediated reactions. The culprit BL varies according to consumption patterns, with amoxicillin (AX) more prevalent in Southern Europe and penicillin V in Scandinavian countries. Nowadays, the combination of AX and clavulanic acid (CLV) is the most highly consumed BL containing medicine worldwide. Both BLs, AX and CLV, can independently be involved in reactions, which poses a diagnostic challenge. In patients with immediate allergic reactions to AX, two patterns of responses have been described, those responding to benzylpenicillin (cross-reactors) and those selective to AX. In addition, selective reactions to CLV account for around 30% of allergic reactions to the combination AX-CLV. These patterns of IgE recognition could be related to differences in the haptenation process, in the immunological response, or in the BL involved in the first sensitization. In this regard, patients with selective responses to CLV are generally younger than those allergic to AX or benzylpenicillin. So far, no evidence of cross-reactivity between CLV and other BLs has been reported. This shows the importance of an accurate diagnosis of CLV allergy, as patients with selective reactions to CLV could take other BLs including AX. Diagnosis can be performed in vivo and in vitro, although no immunoassay currently exists. Research regarding the CLV antigenic determinants and protein conjugates is essential to improve diagnosis. BLs need to covalently bind to a carrier protein to be immunogenic. The antigenic determinant of AX is the amoxicilloyl amide, but CLV leads to unstable structures, many of which are unknown. Moreover, the nature of the BL-protein conjugates plays an important role in IgE recognition. This review aims to summarize current knowledge on the immunochemistry, diagnostic approaches as well as chemical and proteomic studies for both AX and CLV.

Community-acquired bacteremia in Paediatrics: Epidemiology, aetiology and patterns of antimicrobial resistance in a tertiary care centre, Malaysia.

INTRODUCTION: bacteremia continues to be one of the major causes of morbidity and mortality despite the existence of numerous antimicrobial agents. this study aimed to provide a Malaysian perspective on paediatric community-acquired bacteraemia based on the documentation of epidemiology and antimicrobial profile of the isolated pathogens. METHOD: A retrospective study was conducted by analysing clinical details, blood cultures and antimicrobial susceptibility testing results in children between the ages of 0 to 13 years old, who were admitted to selayang Hospital over an 11-year period from 2001 until 2011. there were 222 bacteraemia cases and the median age was 11.7 months. the highest number (39%) of bacteraemia cases occurred between ages one month to one year. the three most commonly isolated aetiological agents were Staphylococcus aureus (17.1%), nontyphoidal Salmonella (16.2%), and Streptococcus pneumoniae (12.6%). Almost 8% of the Staphylococcus aureus isolates were methicillin resistant, while nontyphoidal Salmonella (Nts) isolates demonstrated 18.4%, 10.5% and 2.6% resistance towards ampicillin, trimethoprim-sulfamethoxazole and ciprofloxacin respectively. All Nts isolates were sensitive to ceftriaxone. Streptococcus pneumoniae isolates showed 17.9% resistance to penicillin. skin and soft tissue infections as well as lower respiratory tract infections (63.2%) were the main foci of infections in Staphylococcus aureus bacteraemia. Acute gastroenteritis (80.0%) and pneumonia (60.8%) were the main presentations of Nts and Streptococcus pneumoniae bacteraemia respectively. Overall mortality rate was 8.1%. CONCLUSION: Knowledge on the local epidemiology and antibiotic resistance pattern serves as a significant platform in improving the empiric antibiotic therapy for patients with community acquired bacteraemia.

Hypersensitivity reactions to ß-lactams: relevance of hapten-protein conjugates.

ß-Lactams (BL) are the drugs most frequently involved in allergic reactions. They are classified according to their chemical structure as penicillins, cephalosporins, monobactams, carbapenems, and clavams. All BL antibiotics have a BL ring that is fused to a 5-member or 6-member ring (except in monobactams) and has 1, 2 or 3 side chains (except in clavams). Differences in chemical structure mean that a wide range of BLs are recognized by the immune system, and patients may experience clinical reactions to one BL while tolerating others. Diagnosis is based on skin and in vitro testing, although both display low sensitivity, possibly because they are based on drugs or drug conjugates that are not optimally recognized by the immune system. BLs are haptens that need to bind to proteins covalently to elicit an immune response. These drugs have a high capacity to form covalent adducts with proteins through nucleophilic attack of amino groups in proteins on the BL ring. Allergenic determinants have been described for all BLs, although benzylpenicillin is the most widely studied. Moreover, formation of BL-protein adducts is selective, as we recently demonstrated for amoxicillin, which mainly modifies albumin, transferrin, and immunoglobulin heavy and light chains in human serum. Given the complexity of BL allergy, understanding the immunological mechanisms involved and optimization of diagnostic methods require multidisciplinary approaches that take into account the chemical structures of the drugs and the carrier molecules, as well as the patient immune response.

Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin.

BACKGROUND: Progression from actinic keratosis (AK) to invasive squamous cell carcinoma (iSCC) of the skin is thought to occur after the development of full thickness epidermal neoplasia, as in the classic pathway of cervical cancer. Nevertheless, cutaneous iSCC may also directly arise from a proliferation of atypical basaloid cells limited mostly to the epidermal basal layer (AK I), akin to what happens in the 'differentiated pathway' of iSCC of the vulva, oral cavity and other locations. OBJECTIVE: To evaluate the prevalence of classic and differentiated pathways in the development of cutaneous iSCC. METHODS: The epidermis adjacent to and overlying iSCC, assumed to be representative of pre-existing lesions, was histologically studied in 196 skin biopsy specimens showing iSCC. RESULTS: AK I, AK II and AK III lesions overlying iSCC were present in 63.8%, 17.9% and 18.4% of cases respectively. The corresponding percentages in the epidermis adjacent to iSCC were 77.9%, 6.6% and 8.3% respectively (stage could not be assessed in 8.1% of cases). Focal epidermal ulceration overlying iSCC was seen in 32% of AK I, 28.6% of AK II and 33.3% of AK III instances. Adnexal involvement by atypical keratinocytes (proliferative AK) was present more frequently in cases with overlying AK I (39/125, 31.2%) than with AK II (8/35, 22.9%) and AKII I (5/36, 13.9%). CONCLUSION: Direct invasion from proliferating basaloid atypical keratinocytes limited to the epidermal basal layer (AK I), known as the differentiated pathway, was the most common form of progression to cutaneous iSCC in our series. On the other hand, stepwise progression from AK I to AK II and AK III (classic pathway) was seen to be operative in a substantial proportion of iSCC cases. All AK lesions, irrespective of intraepidermal neoplasia thickness, are therefore potentially invasive and tumour advance along adnexal structures might facilitate iSCC development from AK I lesions.

Impact of limited hamstring flexibility on vertical jump, kicking speed, sprint, and agility in young football players.

This study aims to analyse the impact of limited hamstring flexibility (HF) on specific football skills, such as sprinting and jumping ability, agility, and kicking speed in young football players. Forty-three male football players (aged 14-18) from a semi-professional football academy participated voluntarily in this study. Data about anthropometric measurements, HF (unilateral passive straight-leg raise test: PSLR), vertical jumping ability (countermovement jump: CMJ), sprinting ability (5, 10, 20 m: S5 m, S10 m, S20 m), agility (Balsom agility test: BAT), and kicking speed in terms of ball speed (dominant and non-dominant leg: KSdom and KSnon-dom) were collected. Cluster analysis grouped according to HF, dividing participants into a flexible group (FG, n = 24) and a non-flexible group (NFG, n = 19) in relation to performances on the PSLR test. Despite finding no significant differences between groups in body composition and age, the FG performed better in terms of sprint scores (S5 m: 6.12%, S10 m: 4.09%, S20 m: 3.29%), BAT score (4.11%), CMJ score (10.49%), and scores for KSdom (6.86%) and KSnon-dom (8%) than the NFG. The results suggest that HF is a key factor for performing football-specific skills, such as sprinting, jumping, agility, and kicking in young football players. These results support the rationale that muscle flexibility must be specifically trained in football players beginning at early ages.

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.

[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.

Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved.

BACKGROUND: Hypersensitivity reactions to fluoroquinolones seem to be on the increase, especially immediate type reactions. OBJECTIVE: The aim of this study was to determine whether several conditions, including gender, age, type of reaction, time interval between the reaction and the study, type of symptoms, the specific fluoroquinolone involved in the reaction and previous confirmed hypersensitivity to betalactams or to other drugs were factors contributing to the development of hypersensitivity to fluoroquinolones. METHOD: We analysed retrospectively all patients attending our allergy department between January 2005 and December 2010 because of a reaction associated with fluoroquinolone administration. The diagnosis was confirmed by basophil activation test or drug provocation tests. In accordance with the results, patients were then classified as having hypersensitivity or non-hypersensitivity to fluoroquinolones. RESULTS: A group of 218 patients was evaluated; 69 were confirmed as having hypersensitivity, 146 as non-hypersensitivity and 3 were excluded. Comparisons between groups showed that the allergic patients more often had a previous confirmed hypersensitivity to betalactams (P = 0.029), immediate reactions (P = 0.001) and anaphylaxis (P = 0.000), and moxifloxacin was the fluoroquinolone most frequently involved (P = 0.027). The logistic regression analysis showed three factors associated with the diagnosis of hypersensitivity reactions to fluoroquinolones: previous hypersensitivity to betalactams (OR: 4.571; 95% CI: 0.987-21.171; adjusted OR: 23.654; 95% CI: 1.529-365.853), immediate reactions (OR: 17.333; 95% CI: 4.374-68.691; adjusted OR: 52.493; 95% CI: 6.621-416.200) and reactions induced by moxifloxacin (OR: 3.091; 95% CI: 1.160-8.239; adjusted OR: 13.610; 95% CI: 2.419-76.565). CONCLUSION: In patients who develop reactions to fluoroquinolones, hypersensitivity is more often confirmed in those with immediate reactions and when moxifloxacin is involved. Moreover, patients with hypersensitivity to betalactams are more prone to develop hypersensitivity reactions to fluoroquinolones.

Diagnosis of immediate hypersensitivity reactions to radiocontrast media.

BACKGROUND: No consensus exists on the diagnostic approach for immediate hypersensitivity reactions (IHR) to radiocontrast media (RCM). We analyzed the diagnostic value of a skin test (ST), drug provocation test (DPT) and basophil activation test (BAT) in patients with symptoms compatible with IHR to RCM. METHODS: Ninety patients with symptoms suggestive of IHR to RCM were evaluated. ST with a panel of RCM was performed, and if negative, DPT was carried out with the culprit RCM. If ST or DPT were positive, tolerance was assessed with an alternative RCM and BAT was carried out with the same panel used for ST. RESULTS: Eight (8.9%) cases were confirmed as having IHR, 5 (62.5%) by ST and 3 (37.5%) by DPT. Five from those confirmed as IHR (62.5%) had a positive BAT. CONCLUSIONS: Hypersensitivity to RCM was confirmed in 9%, by ST or DPT. BAT proved a valuable method for diagnosis.

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.

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

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

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.

[Ichthyc biodiversity of seagrass meadows from the Northwest coast of Cariaco Gulf, Venezuela]. / Biodiversidad íctica de praderas de pasto marino de la costa noroeste del Golfo de Cariaco, Venezuela.

Seagrasses are highly productive coastal ecosystems with a high diversity and abundance of fishes, very important to support artisanal fisheries. We analyzed the fish community structure of Thalassia testudinum in the communities of Manzanillo (M) and La Brea (LB), Northwest coast of Cariaco Gulf, Venezuela. Samples were taken monthly (Nov. 2006-Oct. 2007) from each place, using a beach net. A total of 34 810 fishes were captured, grouped into 13 orders, 36 families and 83 species. In both areas (M and LB), the number of species was similar, but a variation in their abundance was found: a total of 55 species and 13 210 organisms for M, and 58 species and 21 600 organisms for LB. The most abundant species and those with the highest biomasses in both areas were: Nicholsina usta, Haemulon boschmae, H. steindachneri, Harengula jaguana, Halichoeres bivittatus and Hemiramphus brasiliensis. The occasional visitors were the most frequent community components with a 59%, the cyclical and permanent residents were represented by the 22% and 19%, respectively. The H'n average for M was of 1.71+/-0.64bits/ind., while for LB was of 1.95+/-0.51bits/ind. The diversity values were directly related to the evenness and inversely related to the dominance. The low values of similarity indexes among localities allow us to assert that these fish communities are dissimilar, because of the structure of each Thalassia meadow and their connectivity with other systems.

Immunoglobulin E-mediated hypersensitivity to amoxicillin: in vivo and in vitro comparative studies between an injectable therapeutic compound and a new commercial compound.

BACKGROUND: Skin testing with amoxicillin (AX) is necessary to diagnose immediate hypersensitivity reactions to this ß-lactam. A commercial AX (DIA-AX) has recently become available for skin testing. OBJECTIVE: The aim of this study was to compare DIA-AX with the injectable form (INJ-AX) in patients who have well-demonstrated IgE-mediated hypersensitivity to AX. METHODS: Chemical characterization using high-performance liquid chromatography of both DIA-AX and INJ-AX reagents was performed. Patients diagnosed with an immediate allergic reaction to AX and a positive skin test to INJ-AX (N=55) were re-evaluated within 6 months by performing skin testing with INJ-AX and DIA-AX. Basophil activation test (BAT) and Radioallergosorbent test (RAST) inhibition assay using both reagents were performed in a selected group of patients. RESULTS: The chemical analysis indicated that both DIA-AX and INJ-AX contained an AX compound with a purity above 95%. In the re-evaluation, 53 (96.4%) cases maintained skin test positivity to INJ-AX and were also positive to DIA-AX. Comparison of the papule area between the two reagents showed no significant differences between both reagents. BAT was performed in 30 samples and was positive to both compounds in 15 cases; no patient had a positive result to just one reagent. RAST inhibition studies using three individual cases and a pool of positive sera showed that the percentage inhibition detected with DIA-AX and INJ-AX was parallel and almost exactly the same. CONCLUSIONS: This study shows that DIA-AX is equivalent to INJ-AX in terms of skin test response, as well as with in vitro immunochemical and biological tests. DIA-AX can therefore be used in the diagnosis of immediate hypersensitivity reactions.