Impact of specific modes of circumferential resection margin involvement in rectal cancer local recurrence: A retrospective study.

PURPOSE: To compare the local recurrence rate and overall survival between patients with circumferential resection margin (CRM) involvement by direct tumor spread and by a tumor within a lymph node. METHODS: A total of 776 patients diagnosed with rectal cancer underwent rectal resection. Patients with CRM involvement by direct tumor spread were named group A. CRM involvement by tumor within a lymph node formed group B. Patient data, including sex, age, pT, pN, stage I-III versus IV, neoadjuvant radiotherapy, adjuvant chemotherapy, carcinoembryonic antigen, primary tumor location, lymph node retrieval, and need for abdominoperineal resection, were compared between both groups. RESULTS: In total, 10.5% of the patients had CRM involvement. Of these, in 57 cases (7.3%), it was by direct tumor spread and in 19 cases (2.4%) by tumor within a lymph node. Other types of CRM involvement were found in six patients. With a mean follow-up of 32.9 months, 18 patients from group A (31.5%) and one patient from group B (5.2%) suffered a local recurrence. Local recurrence-free survival was significantly higher in patients from group B (P = 0.049). Patients in stage I-III (P = 0.037) and from group B ( P = 0.049) had better overall survival. CONCLUSION: Patients with CRM involvement by tumor within a lymph node have a low risk of local recurrence and better overall survival than patients with CRM involvement by direct tumor spread.

Bartonella chomelii is the most frequent species infecting cattle grazing in communal mountain pastures in Spain.

The presence of Bartonella spp. was investigated in domestic ungulates grazing in communal pastures from a mountain area in northern Spain, where 18.3% (17/93) of cattle were found to be positive by PCR combined with a reverse line blot (PCR/RLB), whereas sheep (n = 133) or horses (n = 91) were found not to be infected by this pathogen. Bartonella infection was significantly associated with age, since older animals showed a higher prevalence than heifers and calves. In contrast to other studies, B. chomelii was the most frequent species found in cattle (14/17), while B. bovis was detected in only three animals. Moreover, 18 B. chomelii isolates and one B. bovis isolate were obtained from nine animals. Afterwards, B. chomelii isolates were characterized by a multilocus sequence typing (MLST) method which was adapted in this study. This method presented a high discrimination power, identifying nine different sequence types (STs). This characterization also showed the presence of different STs simultaneously in the same host and that STs had switched over time in one of the animals. In addition, B. chomelii STs seem to group phylogenetically in two different lineages. The only B. bovis isolate was characterized with a previously described MLST method. This isolate corresponded to a new ST which is located in lineage I, where the B. bovis strains infecting Bos taurus subsp. taurus are grouped. Further studies on the dynamics of Bartonella infection in cattle and the potential ectoparasites involved in the transmission of this microorganism should be performed, improving knowledge about the interaction of Bartonella spp. and domestic ungulates.

Chronic stress of rainbow trout Oncorhynchus mykiss at high altitude: a field study.

The stress response of Oncorhynchus mykiss in high-altitude farms in central Mexico was investigated over two seasons: the cool (9·1-13·7° C) dry winter season, and the warmer (14·7-15·9° C), wetter summer season. Fish were subjected to an acute stress test followed by sampling of six physiological variables: blood cortisol, glucose, lactate, total antioxidant capacity, haemoglobin concentration and per cent packed cell volume (VPC %). Multivariate analyses revealed that lactate and total antioxidant capacity were significantly higher in the summer, when water temperatures were warmer and moderate hypoxia (4·9-5·3 mg l(-1) ) prevailed. In contrast, plasma cortisol was significantly higher in the winter (mean ± s.e.: 76·7 ± 4·0 ng ml(-1) ) when temperatures were cooler and dissolved oxygen levels higher (6·05-7·9 mg l(-1) ), than in the summer (22·7 ± 3·8 ng ml(-1) ). Haemoglobin concentrations (mg dl(-1) ) were not significantly different between seasons, but VPC % was significantly higher in the summer (50%) than in the winter (35%). These results suggest that in summer, effects of high altitude on farmed fish are exacerbated by stresses of high temperatures and hypoxia, resulting in higher blood lactate, increased total antioxidant capacity and elevated VPC % levels.

A minimally invasive procedure for blood extraction from Xenopus laevis allows follow up studies without euthanasia.

Blood extraction is extremely important for the development of scientific research; however, the existing methods for amphibian´s blood sampling are invasive, mainly leading to the euthanasia of the animal. Therefore, less intrusive methods that allow the obtention of multiple samples from the same individual, are needed as an alternative to the common methods available. Hence, the aim of this study was to propose a minimally invasive method for obtaining blood from the hind leg of Xenopus laevis, that allows continuous sampling without compromising the wellbeing of the organisms. With this method, it was possible to extract blood and plasma from adults and juveniles, and the amount of sample was enough to perform biochemical and molecular assays to assess the viability of the blood. The results also revealed that this method is a convenient alternative to obtain blood without affecting the welfare of the experimental organisms, avoiding the cull of the animals, and the samples are viable for their use in follow up studies.

Patient preferences in chronic immune-mediated inflammatory diseases potentially treated with biological drugs: discrete choice analysis using real-world data analysis.

OBJECTIVES: Immune-mediated inflammatory diseases (IMIDs) represent a high burden due to their chronicity, high prevalence, and associated comorbidities. Chronic patients' preferences must be considered in IMIDs treatment and follow-up. The objective of this study was to further understand patient's preferences in private settings. METHODS: A literature review was performed to choose the most relevant criteria for patients. A D-efficient discrete choice experiment was designed to elicit preferences of adult patients with IMIDs and potential biological treatment prescription. Participants were collected from private practices (rheumatology, dermatology, and gastroenterology) from February to May 2022. Patients chose between option pairs, characterized by six health-care attributes, as well as monthly out-of-pocket drug price. Responses were analyzed through a conditional logit model. RESULTS: Eighty-seven patients answered the questionnaire. The most frequent pathologies were Rheumatoid Arthritis (31%) and Psoriatic Arthritis (26%). The most relevant criteria were choosing the preferred physician (OR 2.25 [SD0.26]); reducing time until visit with specialist (OR 1.79 [SD0.20]), access through primary care (OR 1.60 [SD0.08]), and an increase in monthly out-of-pocket price from 100€ to 300€ (OR 0.55 [SD0.06]) and to 600€ (OR 0.08 [SD0.02]). CONCLUSIONS: Chronic IMIDs patients showed a preference toward a faster, personalized service, even with a trade-off in terms of out-of-pocket price.

Boldness and aggressiveness in early and late hatched three-spined sticklebacks Gasterosteus aculeatus.

Levels of boldness and the degree of aggressiveness were compared in juvenile three-spined sticklebacks Gasterosteus aculeatus that had hatched early and late in the breeding season. The most striking result found in this study was that early hatched individuals were bolder when exploring a novel environment than were late-hatched individuals. No differences in levels of aggression between early and late hatchlings were found, but a relationship between boldness and aggressiveness was present regardless of hatching date. The implications of these findings are discussed in the light of research on individual variation in behaviour and the development of behavioural syndromes.

Simultaneous nitrification/denitrification and desulfurization of wastewater polluted with ammonium, COD and sulfide: effectiveness of a new up-flow vertical hybrid reactor.

Industrial wastewater discharges pose an environmental risk. Here, the effectiveness of an up-flow vertical hybrid system, operating with synthetic and industrial wastewater was investigated, as a new approach to perform nitrification/denitrification and desulfurization within a single reactor. The hybrid reactor is divided in two reaction zones, the oxic and anoxic. The removal of chemical oxygen demand (COD), ammonium, and sulfide was investigated, highlighting changes in microbial diversity. The reactor was evaluated at hydraulic residence time (HRT) of 1.6 days, and its performance throughout 180 days is presented in four stages. In stages I-II, high COD and ammonium removal was obtained with synthetic wastewater. In stage-III, sulfide-rich synthetic wastewater did not alter the system, attaining COD, ammonium, and sulfide removal efficiencies of 81, 99.5, and 99.7%, respectively. In the last stage, a mixture of effluents was fed into the reactor at loading rates of 277 mg COD/L-d, 46.5 mg NH4 +-N /L-d, and 15 mg HS--S /L-d. Sulfide and ammonium removals were 100% and 99.9%, respectively. However, low COD removal was observed, being of 51%, and the system removed 97% in terms of BOD5. The structure and microbial diversity also changed. Sulfide feeding, induced the proliferation of sulfur oxidizers like Thiomiscropira and Thiobacillus. Industrial wastewater enhanced the abundance of Pseudomonas (15.53%) and favored the proliferation of new bacteria of the genus Truepera (2.98%) and Alicyclipilus (7.56%). This is the first study reporting simultaneous nitrification/denitrification and desulfurization to remove ammonium, COD and sulfide from complex industrial wastewater using an up-flow vertical hybrid reactor.

Tuberculosis in a Spanish cohort of children living with HIV: the CHOTIS study (Childhood HIV & TB study).

BACKGROUND: Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain.METHODS: Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified. The incidence and clinical presentation were compared in three periods: 1995-1999 (P1, before initiation of combined antiretroviral therapy, cART), 2000-2009 (P2, increase in immigration), and 2010-2016 (P3, decrease in immigration).RESULTS: We included 29 TB cases among 1183 children aged <18 years (2.4%, 243/100 000 person-years). The proportion was stable in P1 and P2 (1.3%), but decreased in P3 (0.8%). The median age at TB diagnosis was 6.4 years (IQR 4-10.6); most children in P3 were aged >10 years (20% vs. 23.1% vs. 83.3%, P = 0.01). TB was diagnosed at HIV presentation in 11/29 children (37.9%). Foreign-born children accounted for respectively 0%, 8% and 67% of the total number of children in each period (P ≤ 0.0001). One third had extrapulmonary TB; four children died (13.8%).CONCLUSION: In our cohort, the incidence of TB-HIV co-infection decreased with decline in immigration. In regions with adequate cART coverage and low TB transmission, paediatric TB-HIV coinfection is uncommon, but associated with significant morbidity. Strategies for TB surveillance, diagnosis and treatment in this vulnerable population should be reinforced.

[Diagnosis of urethritis in men. A 3-year review]. / Diagnóstico microbiológico en varones. Revisión de 3 años.

OBJECTIVES: The aim of this study is to know the prevalence and tendency of microorganisms producing urethritis, in men, in the City Centre of Madrid. METHODS: Cross-sectional study. The urethral samples of 1.248 men were analyzed, for 3 years. The samples were studied for: GRAM stain, when secretion exists; culture in habitual plates; detection of C. trachomatis, U. urealyticum and M. hominis, when there was suspicious, study of T. vaginalis and when suspicious injuries exist, study of virus Herpes simplex. RESULTS: The percentage of positive samples was 22.60%. The isolated microorganisms were: U. urealyticum 7.61%, N. gonorrhoeae 6.33%, C. trachomatis 4.81%, M. hominis 0.24%, H. parainfluenzae 1.76%, H. influenzae 1.12%, Candida spp 0.48%, S. pyogenes 0.16% and Herpes virus simplex (2) 0.08%. Two or more microorganisms were isolated in 1.68%. The percentage of positive samples in 2003 was 17.41% and N. gonorrhoeae the most frequent microorganism (6.22%). In 2004 was 25.57% and the most frequent U. urealyticum (10.18%). In 2005 the 24.50% of the samples were positive and U. urealyticum the most frequent (7.92%). The 79.41% of N. gonorrhoeae were susceptible to all antibiotics tested. It is not found resistance to ceftriaxone, claritromicine and amoxicilline/clavulanic acid. The 11.76% were betalactamase- producing. The 26.47% of Haemophilus spp. were betalactamase- producing and all strains were susceptible to cefotaxime. CONCLUSIONS: The isolated microorganisms most frequently were: U. urealyticum, N. gonorrhoeae and C. trachomatis. There is an increase of 7% of prevalence between the years 2003 and 2005. Ceftriaxone, claritromicine and amoxicilline/clavulanic acid were susceptible to all the strains studied and cefotaxime to all Haemophilus spp.

Three-spined sticklebacks Gasterosteus aculeatus as a model for exploring behavioural biology.

Niko Tinbergen chose the three-spined stickleback Gasterosteus aculeatus for his classic behavioural studies because they are small, robust, common and easy to house in the laboratory under reasonably natural conditions and also because their behaviour, while sufficiently simple to be tractable, is still sufficiently complex to be interesting. An analysis of citation records shows that this was an inspired choice. Research on these small fish has addressed all four of Tinbergen's famous questions (causation, development, functions and evolution) and has contributed to the understanding of many different behavioural systems. The G. aculeatus literature is used here to explore several themes in fundamental behavioural biology (diet choice, shoaling, behavioural syndromes and sexual signalling) and the extent to which research using G. aculeatus has informed both fundamental and applied behavioural biology, the latter in the context of aquaculture research.

Clinical characteristics, prevalence, and factors related to delirium in children of 5 to 14 years of age admitted to intensive care. / Características clínicas, prevalencia y factores asociados al delirium en niños de 5 a 14 años de edad ingresados en cuidados intensivos.

OBJECTIVE: To evaluate the clinical characteristics, prevalence and factors associated with delirium in critical patients from 5 to 14 years of age. DESIGN: An analytical, cross-sectional observational study was made. Delirium was assessed with the Pediatric-Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU) and motor classification was established with the Delirium Rating Scale Revised-98. SETTING: A pediatric Intensive Care Unit. PATIENTS: All those admitted over a one-year period were assessed during the first 24-72h, or when possible in deeply sedated patients. EXCLUSION CRITERIA: Patients in stupor or coma, with severe communication difficulty, subjected to deep sedation throughout admission, and those with denied consent. RESULTS: Twenty-nine of the 156 assessed patients suffered delirium (18.6%) and 55.2% were hypoactive. The neurocognitive alterations evaluated by the pCAM-ICU were similar in the three motor groups. Intellectual disability (OR=17.54; 95%CI: 3.23-95.19), mechanical ventilation (OR=18.80; 95%CI: 4.29-82.28), liver failure (OR=54.88; 95%CI: 4.27-705.33), neurological disease (OR=4.41; 95%CI: 1.23-15.83), anticholinergic drug use (OR=3.23; 95%CI: 1.02-10.26), different psychotropic agents (OR=4.88; 95%CI: 1.42-16.73) and tachycardia (OR=4.74; 95%CI: 1.21-18.51) were associated to delirium according to the logistic regression analysis. CONCLUSION: The frequency of delirium and hypoactivity was high. It is therefore necessary to routinely evaluate patients with standardized instruments. All patients presented with important neurocognitive alterations. Several factors related with the physiopathology of delirium were associated to the diagnosis; some of them are modifiable through the rationalization of medical care.

[Modulation of biomarkers expression (OR, PR and C-erbB2) in breast cancer following neoadjuvant treatment]. / Modulación en la expresión de biomarcadores (RE, RP y C-erbB2) en cáncer de mama tras tratamiento neoadyuvante.

INTRODUCTION: Pre and post-operative oncological therapy in patients with breast cancer is determined, amongst other factors, by hormone receptor status and by c-erbB2 expression. The aim of this study is to determine the influence of neoadjuvant therapy on the expression of oestrogen receptor (OR), progesterone receptor (PR) and c-erbB2. METHODS: Fifty-three patients with breast cancer diagnosed by tru-cut biopsy were studied. Patients with locally advanced carcinoma (20) had preoperative treatment. All patients underwent surgical resection. Expression of OR, PR and c-erbB2 in both the tru-cut biopsy and the gross specimen was compared. RESULTS: We found significant differences in OR, PR expression in both biopsy and gross specimen, between the group of patients who underwent neoadjuvant treatment and the group without pre-surgical treatment. Changes in PR, OR and c-erbB2 status were found between the tru-cut biopsy and the gross specimen, in about 10 to 40% of the cases who received neoadjuvant therapy. These changes had no statistical significance.

[Spondylodiscitis in the autonomus community of Madrid (Spain)]. / Espondilodiscitis en la Comunidad de Madrid.

INTRODUCTION: Spondylodiscitis is a relatively uncommon entity in infancy and childhood, with typical, although non-specific symptoms. The aim of this study was to describe the clinical features at presentation and follow-up in patients diagnosed with spondylodiscitis in hospitals in the Autonomous Community of Madrid. PATIENTS AND METHODS: All cases of spondylodiscitis diagnosed in children in the hospitals of La Paz, Niño Jesús, Gregorio Marañón, Severo Ochoa, Doce de Octubre and Getafe in Madrid were reviewed. Their clinical features, diagnostic tests, treatment and follow-up were analyzed. RESULTS: Twenty children with a mean age of 37 months were studied. The level of disc involvement was L5-S1 in six patients, L2-L3 in five, L3-L4 in four, C6-C7 in two, and D12-L1 in one. The mean time before diagnosis was 20 +/- 16 days. The most frequent symptoms were gait disturbances, limping, or inability to remain seated. Eleven patients had low grade fever (< 38.5 degrees C). Other less specific symptoms were irritability, constipation and abdominal pain. All patients presented moderate leukocytosis without neutrophilia. The mean erythrocyte sedimentation rate was 60 +/- 26. The most frequently used diagnostic tests were conventional spine radiographs, technetium-99m bone scan and magnetic resonance imaging. All patients received antibiotics; three received oral antibiotics only and the remaining patients received intravenous and oral antibiotics. The most frequently prescribed antibiotics were cefuroxime, cloxacillin and amoxicillin-clavulanate. The duration of treatment ranged between 3 and 8 weeks. All patients had a favorable outcome, although in eight, radiological sequelae were observed. CONCLUSIONS: Spondylodiscitis is not exceptional in childhood and awareness of this entity among pediatricians should be increased.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis]. / Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (I): epidemiología y diagnóstico. Tuberculosis congénita.

Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment]. / Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (ii): profilaxis y tratamiento.

In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended.

Protein kinase C in Trypanosoma cruzi epimastigote forms: partial purification and characterization.

A protein kinase C activity from epimastigote forms of Trypanosoma cruzi was characterized. Cytosolic extracts were chromatographed on DEAE-cellulose columns giving two peaks of kinase activity which were eluted at 0.1 and 0.15 M NaCl. The first activity peak requires Ca2+ and phosphatidylserine for activity. Further kinase purification was performed by chromatography on phenyl Sepharose columns. In these columns the enzyme activity was adsorbed in the presence of Ca2+ and eluted with a EGTA-containing buffer. T. cruzi protein kinase C activity preferentially phosphorylated histone H1. It was stimulated by diacylglycerol and phorbol myristate acetate, and inhibited by polymyxin B and staurosporine. After subcellular fractionation and epimastigote cells, the kinase was found to be associated with microsomal and cytosolic fractions.

Biochemical and immunological studies of protein kinase C from Trypanosoma cruzi.

Phorbol ester binding was studied in protein kinase C-containing extracts obtained from Trypanosoma cruzi epimastigote forms. Specific 12-O-tetradecanoyl phorbol 13-acetate, [3H]PMA, or 12,13-O-dibutyryl phorbol, [3H]PDBu, binding activities, determined in T. cruzi epimastigote membranes, were dependent on ester concentration with a Kd of 9x10(-8) M and 11.3x10(-8) M, respectively. The soluble form of T. cruzi protein kinase C was purified through DEAE-cellulose chromatography. Both protein kinase C and phorbol ester binding activities co-eluted in a single peak. The DEAE-cellulose fraction was further purified into three subtypes by hydroxylapatite chromatography. These kinase activity peaks were dependent on Ca2+ and phospholipids and eluted at 40 mM (PKC I), 90 mM (PKC II) and 150 mM (PKC III) phosphate buffer, respectively. Western blot analysis of the DEAE-cellulose fractions, using antibodies against different isoforms of mammalian protein kinase C enzymes, revealed that the parasite expresses high levels of the alpha-PKC isoform. Immunoaffinity purified T. cruzi protein kinase C, isolated with an anti-protein kinase C antibody-sepharose column, were subjected to phosphorylation in the absence of exogenous phosphate acceptor. A phosphorylated 80 kDa band was observed in the presence of Ca2+, phosphatidylserine and diacylglycerol.

Long-term results of silicone tube in filtering surgery for eyes with neovascular glaucoma.

We operated on 59 eyes with advanced neovascular glaucoma (37 eyes in diabetic patients and 22 eyes in patients with central retinal vein occlusion) using a trabeculectomy technique that includes a simple silicone tube as the draining element. Mean (+/- 1 S.D.) intraocular pressure preoperatively was 57 +/- 8.7 mm Hg. During follow-up periods ranging from one to five years, the mean intraocular pressure decreased to 27 +/- 16.5 mm Hg. Adequate control of intraocular pressure (24 mm Hg or less) was achieved in 37 eyes (63%). Only four eyes required enucleation. Nine silicone tubes had to be removed because of necrosis of the scleral flap and conjunctival perforation or because they were expulsed. Surgery relieved the severe ocular pain even when intraocular pressure was not satisfactorily controlled.