Chronic alcohol consumption and withdrawal do not induce cell death in the suprachiasmatic nucleus, but lead to irreversible depression of peptide immunoreactivity and mRNA levels

There is evidence that chronic ethanol treatment (CET) disrupts the biological rhythms of various brain functions and behaviors. Because the suprachiasmatic nucleus (SCN) is widely recognized as the dominant pacemaker of the circadian system, we have examined the effects of CET and withdrawal on the main morphological features and chemoarchitecture of this hypothalamic nucleus. Groups of rats ethanol-treated for 6 and 12 months were compared with withdrawn rats (ethanol-treated for 6 months and then switched to a normal diet for an additional 6 months) and with groups of age-matched control and pair-fed control rats. The volume and the total number of neurons of the SCN were estimated from conventionally stained material, whereas the total number of astrocytes and of neurons containing vasopressin (AVP), vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and somatostatin (SS) were estimated from immunostained sections. The estimates were obtained using unbiased stereological methods, based on Cavalieri’s principle and the optical fractionator. The volume of the SCN and the total number of SCN neurons and astrocytes did not vary among groups. We found, however, that CET induced a significant reduction in the total number of AVP-, VIP-, GRP-, and SS-containing neurons. Withdrawal from alcohol did not reduce but rather augmented the loss of VIP- and GRP-immunoreactive neurons. The CET-induced neurochemical alterations seem to result from a decrease in neuropeptide synthesis, as revealed by the reduction in AVP and VIP mRNA levels demonstrated byin situhybridization with radioactively labeled 48-mer AVP and 30-mer VIP probes. It is thus possible to conclude that the irreversible CET-induced changes in the neurochemistry of the SCN might underpin the disturbances in circadian rhythms observed after long-term alcohol consumption.</jats:p

Nicolau Livedoid Dermatitis following intramuscular benzathine penicillin injection

We report the case of a 64-year-old male presenting with a rapidly enlarging painful violaceous plaque in the left buttock and posterior thigh, following a gluteal intramuscular injection of benzathine penicillin. Associated urinary incontinence and lower left limb paresis were consistent with sciatic and lower sacral nerve damage, as confirmed by electromyography. Additional underlying muscular damage was observed in ultrasound and computer tomodensitometry scans and supported by high serum levels of creatine kinase and lactate dehydrogenase. Aggressive treatment was performed with fluid expansion, intravenous steroid bolus, vasodilators and anticoagulation, resulting in slow improvement of cutaneous and muscular lesions. However, no significant effect was observed on neurologic dysfunction after 6 months of regular neuromuscular rehabilitation. Nicolau Livedoid Dermatitis is a rare and potentially fatal condition showing variable levels of tissue impairment and unpredictable course and prognosis. Specific treatment is not consensual and the efficacy of any particular treatment remains to be established

Utilização de própolis como alternativa no controlo de mastites para garantir a qualidade do leite e proteção da saúde pública.

Os antimicrobianos e antisséticos são utilizados para o controlo das mastites. Esta prática conduz a eliminação de resíduos no leite além de induzir a pressão de seleção sobre estirpes resistentes a antimicrobianos. A própolis é uma massa, utilizada para proteger as colmeias das abelhas (Apis mellifera), formada por resinas retiradas de vários vegetais, selecionadas de forma natural pelas abelhas. Este produto altamente variável, consoante os vegetais utilizados, apresenta colorações diversas e também qualidades antimicrobianas variáveis. O objetivo deste estudo foi testar a suscetibilidade, de isolados de Staphylococccus aureus provenientes de amostras de leite de cabras e ovelhas com mastite, a 16 antimicrobianos utilizados em Portugal no controlo desta doença, e analisar “in vitro” a ação antimicrobiana de extratos etanólicos de própolis (EEP).FCT – Fundação para a Ciência e a Tecnologia no âmbito do Projecto UID/AGR/00115/2013. M. Laranjo agradece a bolsa de Pós-Doutoramento da FCT (SFRH/BPD/108802/2015)

Influenza A(H1N1)pdm09 Resistance and Cross-Decreased Susceptibility to Oseltamivir and Zanamivir Antiviral Drugs

Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs

CARD15 Mutations and Perianal Fistulating Crohn’s Disease: Correlation and Predictive Value of Antibiotic Response

BACKGROUND: CARD15 mutations alter bowel immunity and increase susceptibility to Crohn's disease (CD). However, the relation between these mutations and Crohn's perianal fistulas has not been fully clarified. AIMS: To assess whether CARD15 mutations are associated with risk of developing Crohn's perianal fistulas and whether these mutations are predictors of the response of perianal fistulas to antibiotics. METHODS: CARD15 mutations were investigated in 203 consecutive CD patients. Presence/absence of history of perianal fistula was recorded. Patients with history of perianal fistula were divided into two groups (with/without CARD15 mutations), and response to antibiotics was evaluated in both groups. RESULTS: Of the 203 patients, 60 (29.6%) showed at least one CARD15 mutation and 55 (27.1%) had history of perianal fistula. History of perianal fistula was identified in 13 (21.7%) patients with mutations and in 42 (29.4%) patients without mutations (P = 0.260). Mean age at diagnosis of first perianal fistula was similar in patients with/without CARD15 mutations (28.7 +/- 9.8 versus 29.7 +/- 10.1 years, P = 0.758). Average time between disease onset and diagnosis of first perianal fistula was also similar in the two groups (4.6 +/- 5.1 versus 5.0 +/- 5.9 years, P = 0.816). Response of perianal fistulas to antibiotics (metronidazole alone or combined with ciprofloxacin) was significantly higher in patients without CARD15 mutations (7.7% versus 40.5%, P = 0.041). CONCLUSIONS: In CD, CARD15 mutations are not associated with risk of developing perianal fistulas or with time of their outbreak. Nevertheless, patients with perianal fistulas and CARD15 mutations showed worse response to antibiotics

An Efficient Local Search for Partial Latin Square Extension Problem

A partial Latin square (PLS) is a partial assignment of n symbols to an nxn grid such that, in each row and in each column, each symbol appears at most once. The partial Latin square extension problem is an NP-hard problem that asks for a largest extension of a given PLS. In this paper we propose an efficient local search for this problem. We focus on the local search such that the neighborhood is defined by (p,q)-swap, i.e., removing exactly p symbols and then assigning symbols to at most q empty cells. For p in {1,2,3}, our neighborhood search algorithm finds an improved solution or concludes that no such solution exists in O(n^{p+1}) time. We also propose a novel swap operation, Trellis-swap, which is a generalization of (1,q)-swap and (2,q)-swap. Our Trellis-neighborhood search algorithm takes O(n^{3.5}) time to do the same thing. Using these neighborhood search algorithms, we design a prototype iterated local search algorithm and show its effectiveness in comparison with state-of-the-art optimization solvers such as IBM ILOG CPLEX and LocalSolver.Comment: 17 pages, 2 figure

CARD15 mutations and colorectal cancer in a South European country

PURPOSE: CARD15 mutations are associated with higher susceptibility to Crohn's disease (CD) and longstanding colonic CD increases the risk of developing colorectal cancer (CRC). The relation between these mutations and sporadic CRC remains controversial. The aim of this study was to assess whether germline and/or somatic CARD15 mutations are risk factors for sporadic CRC in Portugal and whether there are genotype-phenotype correlations in these patients. METHODS: The three main CARD15 mutations (R702W, G908R and 3020insC) were researched in 112 sporadic CRC patients and 152 healthy subjects. RESULTS: Overall, CARD15 mutations were found in 18 patients (16.1%) and in 15 controls (9.9%; p = 0.132). Individually, the incidence of R702W was significantly higher in patients than in controls (12.5% vs. 5.3%, p = 0.035), whereas the genotype frequencies for G908R (2.7% vs. 3.3%) and 3020insC (0.9% vs. 1.3%) were not statistically different between the two groups. Entire genotypic agreement was found in patients genotyped for blood and neoplastic DNA. A significantly higher incidence of CARD15 mutations was detected in patients with CRC diagnosed under 60 years old (28.6% vs. 10.4%, p = 0.015) and in female patients (24.4% vs. 10.4%, p = 0.048). No associations were found between CARD15 mutations and family history, symptoms or CRC pathologic characteristics. CONCLUSIONS: The CARD15 R702W variant might be a predisposing factor to sporadic CRC in Portugal, particularly in patients under 60-years old and in female patients. This susceptibility appears to be linked with germline CARD15 mutations. Nevertheless, we have found no evidence that CARD15 mutations predict the pathologic characteristics of CRC

A hysteretic multiscale formulation for nonlinear dynamic analysis of composite materials

This article has been made available through the Brunel Open Access Publishing Fund.A new multiscale finite element formulation is presented for nonlinear dynamic analysis of heterogeneous structures. The proposed multiscale approach utilizes the hysteretic finite element method to model the microstructure. Using the proposed computational scheme, the micro-basis functions, that are used to map the microdisplacement components to the coarse mesh, are only evaluated once and remain constant throughout the analysis procedure. This is accomplished by treating inelasticity at the micro-elemental level through properly defined hysteretic evolution equations. Two types of imposed boundary conditions are considered for the derivation of the multiscale basis functions, namely the linear and periodic boundary conditions. The validity of the proposed formulation as well as its computational efficiency are verified through illustrative numerical experiments

Limited Antineutrophil Cytoplasmic Antibodies (ANCA)-Negative Granulomatosis With Polyangiitis: Successful Response to Rituximab

Granulomatosis with polyangiitis (GPA), a systemic vasculitis, is commonly characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a subset of patients with limited disease may exhibit ANCA negativity. In this article, we report the case of a 40-year-old female diagnosed with GPA with intolerance to methotrexate titration and glucocorticoid therapy, leading to the initiation of rituximab treatment. Subsequently, the patient exhibited sustained clinical, laboratory, and radiological improvement. The identification of limited GPA has important therapeutic implications as the effectiveness of the medical treatment in ANCA-negative GPA may differ. Rituximab has emerged as an optimal treatment, irrespective of ANCA status, offering prolonged responses and a favorable tolerance profile in these patients.info:eu-repo/semantics/publishedVersio