IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin‐4 (IL‐4), interleukin‐5 (IL‐5) and interleukin‐13 (IL‐13). Interleukin‐33 (IL‐33) appears to be a potent inducer of Th2 immune response. This occurs when IL‐33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL‐5 and IL‐13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53–0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL‐5 production (OR 1.36, 95% CI: 1.09–1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07–1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08–2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.     

Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes,BDNF, and astrocytes

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug’s sustained antidepressant-like effects.     

Splenic lymphangioma: A rare adult case with imaging features

This paper describes imaging findings of splenic lymphangioma in a 59-year-old female patient, together with a critical review of the literature. Lymphangioma exclusively in the spleen in adults is a rare event and, in most cases, it is asymptomatic.     

Comprehensive seroprofiling of sixteen B. burgdorferi OspC: Implications for Lyme disease diagnostics design

Early diagnosis of Lyme disease (LD) is critical to successful treatment. However, current serodiagnostic tests do not reliably detect antibodies during early infection. OspC induces a potent early immune response and is also one of the most diverse proteins in the Borrelia proteome. Yet, at least 70% of the amino acid sequence is conserved among all 21 known OspC types. We performed a series of comprehensive seroprofiling studies to select the OspC types that have the most cross-reactive immunodominant epitopes. We found that proteins belonging to seven OspC types detect antibodies from all three infected host species regardless of the OspC genotype of the infecting strain. Although no one OspC type identifies all seropositive human samples, combinations of as few as two OspC proteins identified all patients that had anti-OspC antibodies.     

Suicide behavior and neuropsychological assessment of type I bipolar patients

BackgroundNeuropsychological deficits are often described in patients with bipolar disorder (BD). Some symptoms and/or associated characteristics of BD can be more closely associated to those cognitive impairments. We aimed to explore cognitive neuropsychological characteristics of type I bipolar patients (BPI) in terms of lifetime suicide attempt history.MethodWe studied 39 BPI outpatients compared with 53 healthy controls (HC) matched by age, educational and intellectual level. All subjects were submitted to a neuropsychological assessment of executive functions, decision-making and declarative episodic memory.ResultsWhen comparing BDI patients, regardless of suicide attempt history or HC, we observed that bipolar patients performed worse than controls on measures of memory, attention, executive functions and decision-making. Patients with a history of suicide attempt performed worse than non-attempters on measures of decision-making and there were a significant negative correlation between the number of suicide attempts and decision-making results (block 3 and net score). We also found significant positive correlation between the number of suicide attempts and amount of errors in Stroop Color Word Test (part 3).LimitationsThe sample studied can be considered small and a potentially confounding variable – medication status – were not controlled.ConclusionOur results show the presence of neuropsychological deficits in memory, executive functions, attention and decision-making in BPI patients. Suicide attempts BPI scored worse than non-suicide attempt BPI on measures of decision-making. More suicide attempts were associated with a worse decision-making process. Future research should explore the relationship between the association between this specific cognitive deficits in BPIs, serotonergic function and suicide behavior in bipolar patients as well other diagnostic groups.     

Laparoscopic surgical staging of locally advanced cervix cancer (IB2 to IVA): initial experience

Introduction and objectives

Cervical cancer incidence worldwide is about 500,000 new cases per year with most of them being detected at a locally advanced stage. Many studies have shown the need to look for extra-pelvic disease when planning appropriate therapy. We performed surgical staging by laparoscopy in 43 cases of cervical cancer at stages IB2 to IVa and evaluated our initial results.

Materials and methods

Between February 2008 and May 2010, we selected 43 patients with histologically confirmed cervical cancer at stages IB2 to IVA with a Karnosfsky index > 70. We classified the tumors according to the FIGO (International Federation of Gynecology and Obstetrics) stage and performed tomographic evaluations of the abdomen to select patients without signs of peritoneal or para-aortic tumor spread. We performed a laparoscopic evaluation of the peritoneal cavity and para-aortic lymph nodes by an extra-peritoneal route. We did not use tweezers or disposable energy seals.

Results

The mean surgical time was 130.8 min. The mean blood loss was 111.5 ml. There was no conversion to laparotomy for any case. We describe a case with peritoneal implants that was classified as IVB.We removed an average of 16.4 lymph nodes; nine cases had para-aortic lymph node metastases.

Conclusion

Laparoscopic surgical staging diagnosed 23.3% of cases with peritoneal spread of the tumor or extra-pelvic lymph node metastases. In this study, we could better define the lymph node status through laparoscopic surgical staging and could therefore recommend more suitable adjuvant therapy for patients with locally advanced cervical cancer.     

Seasonal analysis and acaricidal activity of the thymol-type essential oil of Ocimum gratissimum and its major constituents against Rhipicephalus microplus (Acari: Ixodidae)

Parasitology Research - The tick Rhipicephalus microplus affects cattle health, with production loss in tropical and subtropical regions. Moreover, the use of commercial acaricides has been reduced...     

Effects of auditory training in individuals with high-frequency hearing loss

OBJECTIVE:To determine the effects of a formal auditory training program on the behavioral, electrophysiological and subjective aspects of auditory function in individuals with bilateral high-frequency hearing loss.METHOD:A prospective study of seven individuals aged 46 to 57 years with symmetric, moderate high-frequency hearing loss ranging from 3 to 8 kHz was conducted. Evaluations of auditory processing (sound location, verbal and non-verbal sequential memory tests, the speech-in-noise test, the staggered spondaic word test, synthetic sentence identification with competitive ipsilateral and contralateral competitive messages, random gap detection and the standard duration test), auditory brainstem response and long-latency potentials and the administration of the Abbreviated Profile of Hearing Aid Benefit questionnaire were performed in a sound booth before and immediately after formal auditory training.RESULTS:All of the participants demonstrated abnormal pre-training long-latency characteristics (abnormal latency or absence of the P3 component) and these abnormal characteristics were maintained in six of the seven individuals at the post-training evaluation. No significant differences were found between ears in the quantitative analysis of auditory brainstem responses or long-latency potentials. However, the subjects demonstrated improvements on all behavioral tests. For the questionnaire, the difference on the background noise subscale achieved statistical significance.CONCLUSION:Auditory training in adults with high-frequency hearing loss led to improvements in figure-background hearing skills for verbal sounds, temporal ordination and resolution, and communication in noisy environments. Electrophysiological changes were also observed because, after the training, some long latency components that were absent pre-training were observed during the re-evaluation.     

Degradable particulate composite reinforced with nanofibres for biomedical applications

Nanofibre-based structures and their composites are increasingly being studied for many biomedical applications, including tissue engineering scaffolds. These materials enable architectures resembling the extracellular matrix to be obtained. The search for optimized supports and carriers of cells is still a major challenge for the tissue engineering field. The main purpose of this work is to develop a novel composite structure that combines microparticles and nanofibres in reinforced polymeric microfibres. This innovative combination of materials is obtained by melting extrusion of a particulate composite reinforced with chitosan nanofibre meshes (0.05 wt.%) produced by the electrospinning technique. The reinforced microfibres were analysed by scanning electron microscopy and showed a considerable alignment of the chitosan nanofibres along the longitudinal main axis of the microfibre composite structure. The tensile mechanical properties revealed that the introduction of the nanofibre reinforcement in the particulate microfibre composite increased the tensile modulus by up to 70%. The various structures were subjected to swelling and degradation tests immersed in an isotonic saline solution at 37 °C. The presence of chitosan nanofibres in the particulate microfibres enhances the water uptake by up to 24%. The combination of good mechanical properties and enhanced degradability of the developed structures is believed to have great potential for various biomedical applications, including three-dimensional fibre mesh scaffolds to be applied in the field of bone tissue engineering.