[Findings in brainstem auditory evoked potentials in patients under 2 years of age with a history of intraventricular haemorrhage]. / Hallazgos en los potenciales evocados auditivos del tallo cerebral en pacientes menores de 2 años con antecedente de hemorragia intraventricular.

INTRODUCTION: There are few studies that describe the results of auditory pathway assessment in patients with a history of intraventricular haemorrhage (IVH) during the early years of life. Hypoacusis can occur from the earliest stages of IVH. Brainstem auditory evoked potentials (BAEPs) are a useful tool for diagnosing auditory pathway disorders in early childhood. The aim of the present study was to describe the BAEPs findings in patients under 2 years of age with a history of IVH. PATIENTS AND METHODS: We conducted a retrospective observational study in patients under 2 years of age with a history of IVH referred to our hospital for BAEPs over a period of three years. Patients with genetic syndromes associated with hypoacusis were excluded. BAEPs were used to evaluate the presence or absence of any bioelectrical response and latencies of waves I, III and V, as well as of the intervals I-III, III-V and I-V, and also their morphology, amplitude, synchrony and reproducibility. A descriptive analysis was carried out with the calculation of frequencies and percentages. RESULTS: A total of 122 patients were included. Fifty-one per cent of them had a history of Grade I IVH; 42%, Grade II; and 7%, Grades III or IV. A bioelectrical response was obtained in 243 auditory pathways (99.6%). The morphology was found to be altered in 6.2% of the auditory pathways, while amplitudes were decreased in 2.5% of those tested. Latencies for waves I and III were found to be prolonged in 2% and for wave V in 3.6% of patients. The hearing threshold was normal in 64.8%, and 35.2% of cases presented hypoacusis. CONCLUSIONS: The prevalence of hypoacusis was high in the sample analysed. Systematic follow-up using BAEPs is recommended in order to detect and treat problems in the auditory pathway in patients with IVH in a timely manner.

TITLE: Hallazgos en los potenciales evocados auditivos del tallo cerebral en pacientes menores de 2 años con antecedente de hemorragia intraventricular.Introducción. Existen pocos estudios que describan los resultados de la evaluación de la vía auditiva en pacientes con antecedente de hemorragia intraventricular (HIV) durante los primeros años de vida. La hipoacusia puede presentarse desde los grados iniciales de la HIV. Los potenciales evocados auditivos del tallo cerebral (PEATC) son una herramienta útil para diagnosticar alteraciones de la vía auditiva en la infancia temprana. El objetivo del presente estudio fue describir los hallazgos en los PEATC en pacientes menores de 2 años con antecedente de HIV. Pacientes y métodos. Es un estudio observacional retrospectivo realizado en pacientes menores de 2 años con antecedente de HIV enviados a nuestro hospital para la realización de PEATC en un período de tres años. Se excluyó a pacientes con síndromes genéticos asociados a hipoacusia. A través de los PEATC se evaluó la presencia o la ausencia de respuesta bioeléctrica y latencias de las ondas I, III y V, así como de los intervalos I-III, III-V y I-V, además de su morfología, amplitud, sincronía y la replicabilidad. Se realizó un análisis de tipo descriptivo con cálculo de frecuencias y porcentajes. Resultados. Se incluyó a un total de 122 pacientes. El 51% de ellos tenía antecedente de HIV de grado I; el 42%, de grado II; y el 7%, de grados III o IV. La respuesta bioeléctrica se obtuvo en 243 vías auditivas (99,6%). La morfología se encontró alterada en el 6,2% de las vías auditivas, mientras que las amplitudes estuvieron disminuidas en el 2,5% de las evaluadas. Las latencias para las ondas I y III se encontraron prolongadas en el 2%, y, para la onda V, en el 3,6% de los pacientes. El umbral auditivo fue normal en el 64,8%, y el 35,2% de los casos presentó hipoacusia. Conclusiones. La prevalencia de la hipoacusia fue alta en la muestra analizada. Se recomienda realizar el seguimiento mediante PEATC de forma sistemática con la finalidad de detectar y atender oportunamente problemas de la vía auditiva en pacientes con HIV.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Pharmacokinetic and clinical monitoring through posologic changes in adalimumab intensification regimen from 40 mg every week to 80 mg every other week.

BACKGROUND: Adalimumab dose escalation is often recommended for inflammatory bowel disease patients in cases of loss of response. The usual adalimumab intensification regimen was 40 mg every week. Recently the pharmaceutical companies commercialized the 80mg injection pen. In the biosimilars era, this pen was sold at the same price as the 40mg pen. Due to this and for patient comfort, we proposed that our stable intensified adalimumab patients on a 40mg every-week regimen, change to a dose of 80mg every-other-week. AIM AND METHODS: an observational study was performed to monitor outcome through this posologic change. Clinical, analytic parameters and adalimumab trough levels were prospectively obtained at baseline, 4 and 12 months after posologic change. The evolution of this cohort and calculates savings were described. RESULTS: 13 patients were included in the study and the median time of adalimumab intensification prior to posologic change to 80mg eow was 32 months (IQR 29-63). At 4 months, all patients maintained adalimumab 80mg every-other-week. After month 4, two patients returned to the previous regimen after mild worsening, without significant changes in CRP, calprotectin or adalimumab-trough-levels. At 1 year, adalimumab was stopped in one patient in remission with undetectable levels and positive adalimumab-antibodies. No significant differences in adalimumab-trough-levels were noted before and after the posologic change. Costs fell from 16276 €/patient/year of treatment to 8812.15 €/patient/year of treatment. CONCLUSION: In IBD patients with stable response to adalimumab intensification regimen of 40 mg every-week, changing to 80mg every-other-week seems to maintain response and similar adalimumab-trough-levels. Furthermore, it is cost-saving, although some patients may perceive mild symptoms.

Molecular signatures of atherosclerotic plaques: An up-dated panel of protein related markers.

Atherosclerosis remains the leading cause of ischemic syndromes such as myocardial infarction or brain stroke, mainly promoted by plaque rupture and subsequent arterial blockade. Identification of vulnerable or high-risk plaques constitutes a major challenge, being necessary to identify patients at risk of occlusive events in order to provide them with appropriate therapies. Clinical imaging tools have allowed the identification of certain structural indicators of prone-rupture plaques, including a necrotic lipidic core, intimal and adventitial inflammation, extracellular matrix dysregulation, and smooth muscle cell depletion and micro-calcification. Additionally, alternative approaches focused on identifying molecular biomarkers of atherosclerosis have also been applied. Among them, proteomics has provided numerous protein markers currently investigated in clinical practice. In this regard, it is quite uncertain that a single molecule can describe plaque rupture, due to the complexity of the process itself. Therefore, it should be more accurate to consider a set of markers to define plaques at risk. Herein, we propose a selection of 76 proteins, from classical inflammatory to recently related markers, all of them identified in at least two proteomic studies analyzing unstable atherosclerotic plaques. Such panel could be used as a prognostic signature of plaque instability.

Illicit trade in marine fish catch and its effects on ecosystems and people worldwide.

Illegal, unreported, and unregulated fishing is widespread; it is therefore likely that illicit trade in marine fish catch is also common worldwide. We combine ecological-economic databases to estimate the magnitude of illicit trade in marine fish catch and its impacts on people. Globally, between 8 and 14 million metric tons of unreported catches are potentially traded illicitly yearly, suggesting gross revenues of US$9 to US$17 billion associated with these catches. Estimated loss in annual economic impact due to the diversion of fish from the legitimate trade system is US$26 to US$50 billion, while losses to countries' tax revenues are between US$2 and US$4 billion. Country-by-country estimates of these losses are provided in the Supplementary Materials. We find substantial likely economic effects of illicit trade in marine fish catch, suggesting that bold policies and actions by both public and private actors are needed to curb this illicit trade.

Biological and environmental drivers of trophic ecology in marine fishes - a global perspective.

Dietary niche width and trophic position are key functional traits describing a consumer's trophic ecology and the role it plays in a community. However, our understanding of the environmental and biological drivers of both traits is predominantly derived from theory or geographically restricted studies and lacks a broad empirical evaluation. We calculated the dietary niche width and trophic position of 2,938 marine fishes and examined the relationship of both traits with species' maximum length and geographic range, in addition to species richness, productivity, seasonality and water temperature within their geographic range. We used Generalized Additive Models to assess these relationships across seven distinct marine habitat types. Fishes in reef associated habitats typically had a smaller dietary niche width and foraged at a lower trophic position than those in pelagic or demersal regions. Species richness was negatively related to dietary niche width in each habitat. Species range and maximum length both displayed positive associations with dietary niche width. Trophic position was primarily related to species maximum length but also displayed a non-linear relationship with dietary niche width, whereby species of an intermediate trophic position (3-4) had a higher dietary niche width than obligate herbivores or piscivores. Our results indicate that trophic ecology of fishes is driven by several interlinked factors. Although size is a strong predictor of trophic position and the diversity of preys a species can consume, dietary niche width of fishes is also related to prey and competitor richness suggesting that, at a local level, consumer trophic ecology is determined by a trade-off between environmental drivers and biological traits.

Regulation of lactate dehydrogenase in response to WSSV infection in the shrimp Litopenaeus vannamei.

Lactate dehydrogenase (LDH) is key for anaerobic glycolysis. LDH is induced by the hypoxia inducible factor -1 (HIF-1). HIF-1 induces genes involved in glucose metabolism and regulates cellular oxygen homeostasis. HIF-1 is formed by a regulatory α-subunit (HIF-1α) and a constitutive ß-subunit (HIF-1ß). The white spot syndrome virus (WSSV) induces anaerobic glycolysis in shrimp hemocytes, associated with lactate accumulation. Although infection and lactate production are associated, the LDH role in WSSV-infected shrimp has not been examined. In this work, the effects of HIF-1 silencing on the expression of two LDH subunits (LDHvan-1 and LDHvan-2) in shrimp infected with the WSSV were studied. HIF-1α transcripts increased in gills, hepatopancreas, and muscle after WSSV infection, while HIF-1ß remained constitutively expressed. The expression for both LDH subunits increased in each tissue evaluated during the WSSV infection, translating into increased enzyme activity. Glucose concentration increased in each tissue evaluated, while lactate increased in gills and hepatopancreas, but not in muscle. Silencing of HIF-1α blocked the increase of LDH expression and enzyme activity, along with glucose (all tissues) and lactate (gills and hepatopancreas) concentrations produced by WSSV infection. These results demonstrate that HIF-1 up regulates the expression of LDH subunits during WSSV infection, and that this induction contributes to substrate metabolism in energetically active tissues of infected shrimp.

Long-distance transport of hair lambs: effect of location in pot-belly trailers on thermo-physiology, welfare and meat quality.

Livestock transport exposes animals to a range of potential stressors that may compromise their welfare and final product quality, and those effects typically increase with the distance travelled. In North America, producers often use pot-belly vehicles for long hauls but little is known about their suitability for transporting lambs. We followed two long-distance trips using pot-belly trailers carrying 500 lambs (each) from Northern to Central Mexico in winter, to measure possible effects on animal welfare and meat quality. Sixty lambs per trip were placed at different locations within the pot-belly trailer. Animals were equipped with iButton Thermochron® temperature devices, which registered body temperature throughout pre- and post-slaughter stages. Despite the rather cool winter conditions, lambs placed in the "belly" and "nose" compartments had higher body temperatures at loading, during transport and lairage and after slaughter (carcass temperature). Those lambs also had higher levels of plasma cortisol, glucose and creatine kinase (CK), and a higher neutrophil/lymphocyte ratio. Regarding meat quality, ultimate pH (24 h) was higher in all locations, especially in LT4 location. Overall, the results suggest a link between thermal stress during transport, elevated physiological indicators of stress and poorer meat quality.

Benefits of music therapy on behaviour disorders in subjects diagnosed with dementia: a systematic review. / Beneficios de la musicoterapia en las alteraciones conductuales de la demencia. Revisión sistemática.

INTRODUCTION: Dementia is characterised by cognitive deterioration and the manifestation of psychological and behavioural symptoms, especially changes in perception, thought content, mood, and conduct. In addition to drug therapy, non-pharmacological treatments are used to manage these symptoms, and one of these latter treatments is music therapy. Since this novel technique in non-verbal, it can be used to treat patients with dementia at any stage, even when cognitive deterioration is very severe. Patients' responses to music are conserved even in the most advanced stages of the disease DEVELOPMENT: A literature research was carried out using the following databases: Academic Search Complete, PubMed, Science Direct y Dialnet. The period of publication was 2003 to 2013 and the search keywords were 'Music Therapy, Dementia, Behaviour, Behaviour Disorders y Behavioural Disturbances'. Out of the 2188 studies that were identified, 11 studies met inclusion criteria for the systematic review. CONCLUSIONS: Music therapy is beneficial and improves behavior disorders, anxiety and agitation in subjects diagnosed with dementia.

[Lymphoplasmacytic inflammatory pseudotumor of the liver]. / Pseudotumor inflamatorio hepático linfoplasmocítico.

We present the case of a middle-aged woman with antecedents of cholecystectomy and several episodes of resi-dual coledocolitiasis resolved endoscopically. She attended Emergency Services due to a new clinical picture of abdo-minal pain and alteration of hepatic enzymes. Image tests showed lesions that suggested hepatic abscesses without ruling out a malign origin. Given this doubt it was decided to carry out a thick needle biopsy obtaining a diagnosis of an inflammatory pseudotumour of the liver related to IgG4-related disease. This is an infrequent entity but must be taken into consideration because - unlike malign pathology, which is the main differential diagnosis - its behaviour is benign, with a good evolution with medical treatment. That is why a suitable diagnosis is vital to avoid aggressive, diagnostic-therapeutic procedures.

Anti-inflammatory and cytotoxic activities of Bursera copallifera.

BACKGROUND: The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain. OBJECTIVE: The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. MATERIALS AND METHODS: We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. RESULTS: The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 µg/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 µg/mL, IC50 = 5.7 µg/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 µg/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 µg/mL), whereas DMeL exhibited an IC50 value of 19.9 µg/mL. CONCLUSION: In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera.

FOXL2 copy number changes in the molecular pathogenesis of BPES: unique cohort of 17 deletions.

Blepharophimosis Syndrome (BPES) is an autosomal dominant developmental disorder of the eyelids with or without ovarian dysfunction caused by FOXL2 mutations. Overall, FOXL2deletions represent 12% of all genetic defects in BPES. Here, we have identified and characterized 16 new and one known FOXL2 deletion combining multiplex ligation-dependent probe amplification (MLPA), custom-made quantitative PCR (qPCR) and/or microarray-based copy number screening. The deletion breakpoints could be localized for 13 out of 17 deletions. The deletion size is highly variable (29.8 kb - 11.5 Mb), indicating absence of a recombination hotspot. Although the heterogeneity of their size and breakpoints is not reflected in the uniform BPES phenotype, there is considerable phenotypic variability regarding associated clinical findings including psychomotor retardation (8/17), microcephaly (6/17), and subtle skeletal features (2/17). In addition, in all females in whom ovarian function could be assessed, FOXL2 deletions proved to be associated with variable degrees of ovarian dysfunction. In conclusion, we present the largest series of BPES patients with FOXL2 deletions and standardized phenotyping reported so far. Our genotype-phenotype data can be useful for providing a prognosis (i.e. occurrence of associated features) in newborns with BPES carrying a FOXL2 deletion.

[Breastfeeding and antiinfectious agents]. / Uso de antibióticos y lactancia materna.

Not infrequently an infection or an antibiotic treatment needed by a lactating mother leads to medical advice against breastfeeding. However, advising against breastfeeding increases morbi-mortality risk in the infant. Besides there are few anti-infectious agents not compatible with breastfeeding, and in these cases, there is usually an alternative to treat the mother's illness. Thus it is important for health professionals to be informed of best sources where to look for the best treatment for the mother compatible with breastfeeding. This article offers the reader a review of basic pharmacodynamics which influence drug use in human lactation, an alphabetically ordered list of available anti-infectious agents coded by numbers indicating risk level, and some web recommendations for the interested reader. We hope to offer the interested reader a useful tool which may prevent some cases of physician led abandonment of lactation.

[Posttransplant regression of uremic tumoral calcinosis]. / Regresión postrasplante renal de la calcinosis tumoral urémica.

Uremic tumoral calcinosis is the massive calcium-phosphate deposits in periarticular tissues, usually around large joints. It has been described between 1-7% hemodialysis patients and although its etiopathogenesis is unknown, it is associated to severe hyperparathyroidism, elevation of the serum calcium-phosphorus product or hiperphosphataemia. We describe the case of tumoral calcinosis in the shoulder due to hiperphosphataemia and elevated calcium-phosphorus product, treated with low calcium intensive dialysis and fast relapse that disappears after renal transplantation.

Euchromatic variant 16p+. Implications in prenatal diagnosis.

BACKGROUND: Euchromatic imbalances at the cytogenetic level are usually associated with phenotypic consequences. Among the exceptions are euchromatic variants of chromosome 16 (16p+) with normal phenotype. There is a growing list of euchromatic duplications and deletions involving both G-positive and G-negative bands that seem to be phenotypically neutral, but these euchromatic variants are rare. OBJECTIVE: The aim of this report is to describe a new familial case of euchromatic variant 16p+ and to emphasise the misinterpretation of these rare euchromatic variants particularly when ascertained at prenatal diagnosis. METHODS AND RESULTS: Fluorescence in situ hybridisation with clone RP11-261A7 showed an amplified signal in the larger chromosome 16. This clone contains FLJ43855 gene, similar to sodium- and chloride-dependent creatine transporter. CONCLUSION: So, this 16p+ variant that involves amplification of pseudogenetic sequences is considered a polymorphism in normal individuals.

MLPA vs multiprobe FISH: comparison of two methods for the screening of subtelomeric rearrangements in 50 patients with idiopathic mental retardation.

Subtelomeric rearrangements not visible by conventional cytogenetic analysis have been reported to occur in approximately 5% of patients with unexplained mental retardation (MR). As the prevalence of MR is high, many patients need to be screened for these chromosomal abnormalities routinely. Multiplex ligation-dependent probe amplification (MLPA) is a new technique for measuring sequence dosage, allowing large number of samples to be processed simultaneously and thus significantly reducing laboratory work. We have assessed its performance for the detection of subtelomeric rearrangements by comparing the results with those of our previous multiprobe fluorescence in situ hybridization (FISH) assay. We have tested 50 patients with idiopathic MR, dysmorphic features, congenital malformations, and/or familial history of MR. Our results show a high degree of concordance between the two techniques for the 50 samples tested. On the basis of these results, we conclude that MLPA is a rapid, accurate, reliable, and cost-effective alternative to FISH for the screening of subtelomeric rearrangements in patients with idiopathic MR.