Caspase-6 activity predicts lower episodic memory ability in aged individuals

Caspase-6 (Casp6), a cysteinyl protease that induces axonal degeneration, is activated early in Alzheimer Disease (AD) brains. To determine whether Casp6 activation is responsible for early cognitive impairment, we investigated the abundance of Casp6 activity, paired helical filament–1 (PHF-1) phosphorylated Tau and amyloid beta peptide (Aβ) pathology by immunohistochemistry in the hippocampal formation of aged non–cognitively impaired (NCI) individuals. Casp6 activity was restricted to the entorhinal cortex (ERC) and CA1 regions of the hippocampus. Pathology scores were then correlated with cognitive scores obtained within 1 year of death. Regression analyses revealed that ERC and CA1 Casp6 activity were the main contributor to lower episodic memory performance, whereas ERC PHF-1 pathology predicted lower semantic and working memory performance. Aβ did not correlate with any of the cognitive tests. Because Casp6 activity and PHF-1 pathology are intimately associated with AD pathology and memory decline is an early event in AD, we conclude that Casp6 activity and PHF-1 immunoreactivity in ERC identifies aged individuals at risk for developing AD.     

1002-LB: ACE Polymorphism in asthmatic patients

Aim

The aim of the this study was to analyse if there is an association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism (287 base pairs, on chromosome 17q23, intron 16) with asthma severity . ACE plays a vital role in the renin-angiotensin-system (RAS) which regulates blood pressure by converting angiotensin I into a powerfull vasoconstrictor angiotensin II and could also have a role in bronchoconstriction and airway remodeling in asthmatic disease.

Methods

Asthmatic patients: n = 22;were compared with a control group of n = 206 healthy blood donors. The insertion/deletion (I/D) polymorphism was determined by PCR- Polymerase chain reaction. Control of asthma assessed by validated instrument (ACQ7 and PAQLQ). Statistical analysis was performed with PASW 18, establishing a significance level of p< 0.05. All patients signed an informed consent.

Results

The mean age of the 22 asthmatics was 42.86 ± 20.8 years; 9 females and 13 males; all caucasians; 20 atopic and 2 nonatopic. The mean age of the control-group (n = 206) was 41.05 ± 11.85 years; 70 females and 136 males. In asthmatics the frequencies of the D- Allele (ACE-D) is 0.591 and of the IAllele (ACE-I) is 0.409; in controls: 0.675 and 0.325 respectively. There is no statistical differences between these groups (p = 0.340). Genotypes in the asthmatics- DD: 45.4%; ID: 27.3%; II: 27,3%; in control group- DD:48.1%; ID:38.8%; II: 13.1%. There is no statistical differences between these groups (p = 0,175). In asthmatics, there is no statistical differences in genotype frequencies (p > 0.05) between : atopics and non atopics; controlled and uncontrolled asthma; males and females; and in the different age-groups.

Conclusions

The role of ACE insertion/deletion (I/D) polymorphism, in asthmatic patients is a controversy risk factor to the severity of asthma, but we think that we need a larger sample to infer about its role in remodeling, vascular tonus and bronchoconstriction.     

When do combinatorial mechanisms apply in the production of inflected words?

A central question for theories of inflected word processing is to determine under what circumstances compositional procedures apply. Some accounts (e.g., the dual-mechanism model; Clahsen, 1999 Clahsen, H. 1999. Lexical entries and rules of language: A multidisciplinary study of German inflections. Behavioral and Brain Sciences, 22: 991–1060. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) propose that compositional processes only apply to verbs that take productive affixes. For all other verbs, inflected forms are assumed to be stored in the lexicon in a nondecomposed manner. This account makes clear predictions about the consequences of disruption to the lexical access mechanisms involved in the spoken production of inflected forms. Briefly, it predicts that nonproductive forms (which require lexical access) should be more affected than productive forms (which, depending on the language task, may not). We tested these predictions through the detailed analysis of the spoken production of a German-speaking individual with an acquired lexical impairment resulting from a stroke. Analyses of response accuracy, error types, and frequency effects revealed that combinatorial processes are not restricted to verbs that take productive inflections. On this basis, we propose an alternative account, the stem-based assembly model (SAM), which posits that combinatorial processes may be available to all stems and not only to those that combine with productive affixes.     

Human papillomavirus infection among sexual partners attending a Sexually Transmitted Disease Clinic in Rio de Janeiro, Brazil

Cervical cancer is a major source of illness and death among women worldwide and genital infection with oncogenic human papillomavirus (HPV) its principal cause. There is evidence of the influence of the male factor in the development of cervical neoplasia. Nevertheless, the pathogenic processes of HPV in men are still poorly understood. It has been observed that different HPV types can be found among couples. The objective of the present study was to investigate HPV infections in female patients (n = 60 females/group) as well as in their sexual partners and to identify the concordance of HPV genotypes among them. By using the polymerase chain reaction, we detected a 95% prevalence of HPV DNA in women with cervical intraepithelial neoplasia (CIN) compared to 18.3% in women with normal cervical epithelium, with a statistically significant difference (P < 0.001). The HPV DNA prevalence was 50% in male partners of women with CIN and 16.6% in partners of healthy women. In the control group (healthy women), only 9 couples were simultaneously infected with HPV, and only 22.2% of them had the same virus type, showing a weak agreement rate (kappa index = 0.2). Finally, we observed that HPV DNA was present in both partners in 30 couples if the women had CIN, and among them, 53.3% shared the same HPV type, showing moderate agreement, with a kappa index of 0.5. This finding supports the idea of circulation and recirculation of HPV among couples, perpetuating HPV in the sexually active population, rather than true recurrences of latent infections.     

Treatment with Low Doses of Polyclonal Immunoglobulin Improves B Cell Function During Immune Reconstitution in a Murine Model

Propose

After autologous stem cell transplantation (ASCT) the immunological B cell compartment recovers slowly. Delays on the recovery of B cell function after autologous stem cell transplantation are due to the low lymphocytes count and to their intrinsic dysfunction.

Methods

We studied the in vivo B cell reconstitution after ASCT examining the independent effect of polyclonal IgG (PolyIg), Fab or Fc fragments infusions in a murine animal model during a period of 12 weeks. These molecules were used in low doses, mimicking the recommended use of IVIg in the case of hypogammaglobulinemia in humans. Flow cytometry analysis and ELISA tests were conducted to monitor the reconstitution of B cells and serum immunoglobulin production. Panama blot and PCA factor 1 analysis were used to study the kinetics of immunoglobulin repertoires reconstitution. Mechanistic studies were also performed using in vitro cell culture.

Results

During follow-up after ASCT, peripheral B cells expand independently of treatment, correcting the immediate increase in sBAFF (soluble B cell activating factor) induced by previous intense myeloablation. Treatments with Fab and Fc fragments infusions promote significant IgM and IgG production comparing to control. Although the complete recovery of antibody repertoire is only achieved at the end of follow-up after ASCT, there is an earlier and significantly stronger recovery in the treated mice, which is evident at 9 weeks after ASCT. At 30 weeks after ASCT, normal values of antibody repertoire were detected in all individuals. Mechanistic studies show that Fab and Fc fragments promote IgG1 production by indirect pathways.

Conclusions

The results presented here demonstrate that polyclonal immunoglobulin indirectly improves the function of the reconstituted B cells and their IgG production by means of Fc-mediated effects on bystander cells. These results further stimulate the discussion about the advantages of IVIg therapy during immune reconstitution after human ASCT.     

Working memory and emotional interpretation bias in a sample of Syrian refugee adolescents

The number of adolescent refugees around the world has been continuously increasing over the past few years trying to escape war and terror, among other things. Such experience not only increases the risk for mental health problems including anxiety, depression, and post-traumatic stress disorder (PTSD), but also may have implications for socio-cognitive development. This study tested cognitive-affective processing in refugee adolescents who had escaped armed conflict in Syria and now resided in Istanbul, Turkey. Adolescents were split into a high trauma (n = 31, 12 girls, mean age = 11.70 years, SD = 1.15 years) and low trauma (n = 27, 14 girls, mean age = 11.07 years, SD = 1.39 years) symptom group using median split, and performed a working memory task with emotional distraction to assess cognitive control and a surprise faces task to assess emotional interpretation bias. The results indicated that high (vs. low) trauma symptom youth were ~ 20% worse correctly remembering the spatial location of a cue, although both groups performed at very low levels. However, this finding was not modulated by emotion. In addition, although all youths also had a ~ 20% bias toward interpreting ambiguous (surprise) faces as more negative, the high (vs. low) symptom youth were faster when allocating such a face to the positive (vs. negative) emotion category. The findings suggest the impact of war-related trauma on cognitive-affective processes essential to healthy development.

     

Low RKIP expression associates with poor prognosis in bladder cancer patients

Urothelial bladder cancer (UBC) is a heterogeneous type of disease. It is urgent to screen biomarkers of tumour aggressiveness in order to clarify the clinical behaviour and to personalize therapy in UBC patients. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor, and its downregulation is associated with metastatic events in an increasing number of solid tumours. We evaluated the clinical and prognostic significance of RKIP expression in patients with high risk of progression UBC. Using immunohistochemistry, we determined RKIP expression levels in a series of 81 patients with high-grade pT1/pTis or muscle-invasive UBC. Staining of CD31 and D2-40 was used to assess blood and lymphatic vessels, in order to distinguish between blood and lymphatic vessel invasion (LVI). We found that 90 % of pT1/pTis tumours, 94 % of non-muscle invasive papillary tumours and 76 % of the cases without LVI occurrence expressed RKIP in >10 % of cells. In this group, we observed a subgroup of tumours (42 %) in which the tumour centre was significantly more intensely stained than the invasion front. This heterogeneous pattern was observed in 63 % of the cases with LVI. Low RKIP expression was associated with poorer 5-year disease-free and overall survival rates, and remained as an independent prognostic factor for disease-free survival. Loss of RKIP expression may be an important prognostic factor for patients with high risk of progression bladder cancer.     

COVID-19 Management in Clinical Dental Care Part II: Personal Protective Equipment for the Dental Care Professional

Background: Facing the coronavirus disease 2019 (COVID-19) challenge on a global level, dental care professionals are encouraged to optimize universal precautions and adopt measures that ensure protection against infection by contaminated aerosols and droplets. Although aerosol transmission is possible, direct contact through large droplets is probably responsible for the vast majority of transmissions. Methods: This paper is the second of a series of 3 on the management of COVID-19 in clinical dental care settings and aims to describe the selection and use of personal protection equipment (PPE) by dental care professionals (DCP), with consideration of the level of risk associated with the planned procedures. PPE selection depends directly on the local epidemiological setting, the patient's characteristics, and the level of risk of the planned procedures. The procedures performed in the office environment are classified as low-, moderate-, or high-risk. Moderate risk includes 2 further sublevels associated with the cleaning, disinfection, and sterilization of materials for clinical procedures that do not generate aerosols. The training of DCP on how to properly don (put on) and doff (remove) PPE is as important as choosing the appropriate PPE because it can be associated with a risk of infection. Discussion: When there is limited availability of PPE, measures should be adjusted to the risk associated with the intervention. Assuming that an effective COVID-19 vaccine will be developed, once it becomes widely available for DCP, PPE requirements will likely be different. Conclusion: The proper use of PPE, together with the adoption of other operational procedures, can provide effective protection against microorganisms being transmitted via body fluids or in the air.