Molecular and Functional Characterization of Histone Derived Antimicrobial Peptides from Marine Organisms

Antimicrobial peptides (AMPs) are gene encoded, small sized, generally cationic, amphiphathic peptides characterized by antimicrobial activity against bacteria, fungi, viruses and other pathogens. They are a major component of the innate immune defense system of almost all living organisms, ranging from bacteria to humans and represent the first line of defense against the invading microbial pathogens (Boman, 1995; Zasloff, 2002). Antimicrobial peptides represent a heterogeneous group displaying multiple modes of action that are determined by the sequence and concentration of peptides. Their remarkable specificity for prokaryotes with low toxicity for eukaryotic cells has favored their investigation and exploitation as new antibiotics

Chief Medical Officer's Report - Evidential Base and Clinical Practice Aspects of Congenital Cardiac Services (August 2013) (PDF 77KB)

Report on Evidential Base and Clinical Practice Aspects of Congenital Cardiac Services The principle drivers that should determine the optimal arrangements for the provision of congenital cardiac services, including  paediatric and adult cardiac surgery, for the population of Northern Ireland is how best those services can be configured to ensure the safest possible care that is of the highest quality possible in order to optimise outcomes and experience for patients and carers. Of necessity, this requires consideration of all requisite supporting services and arrangements to ensure access across the continuum of care. Such a configuration should support safe, high quality service provision on an on-going basis i.e. ensure sustainability as far as can be determined. In addressing this issue, consideration to the changing profile of population need and the evolving nature specialist services is required.  

The 10th Anniversary of the Junior Members and Affiliates of the European Academy of Allergy and Clinical Immunology

This year is the 10th anniversary of the European Academy of Allergy and Clinical Immunology (EAACI) Junior Members and Affiliates (JMAs). The aim of this review is to highlight the work and activities of EAACI JMAs. To this end, we have summarized all the initiatives taken by JMAs during the last 10 yr. EAACI JMAs are currently a group of over 2380 clinicians and scientists under the age of 35 yr, who support the continuous education of the Academy's younger members. For the past decade, JMAs enjoy a steadily increasing number of benefits such as free online access to the Academy's journals, the possibility to apply for Fellowships and the Mentorship Program, travel grants to attend scientific meetings, and many more. In addition, JMAs have been involved in task forces, cooperation schemes with other scientific bodies, organization of JMA focused sessions during EAACI meetings, and participation in the activities of EAACI communication platforms. EAACI JMA activities represent an ideal example of recruiting, training, and educating young scientists in order for them to thrive as future experts in their field. This model may serve as a prototype for other scientific communities, several of which have already adapted similar policies.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

Determining day length and temperature regulation of flowering: a molecular and modelling approach

Thesis (Ph.D.)--University of Washington, 2016-08

Association between vaginal bacterial microbiota and the presence and clinical presentation of vulvovaginal candidiasis

Thesis (Master's)--University of Washington, 2016-08

Survivorship and Clinical Outcome of the Minimally Invasive Uniglide Medial Fixed Bearing, All-polyethylene Tibia, Unicompartmental Knee Arthroplasty at a Mean Follow-up of 7.3 Years

Background: Medial UKA performed in England and Wales represents 7 to 11% of all knee arthroplasty procedures, and is most commonly performed using mobile-bearing designs. Fixed bearing eliminates the risk of bearing dislocation, however some studies have shown higher revision rates for all-polyethylene tibial components compared to those that utilize metal-backed implants. The aim of the study is to analyse survivorship and maximum 8-year clinical outcome of medial fixed bearing, Uniglide unicompartmental knee arthroplasty performed using an all-polyethylene tibial component with a minimal invasive approach. Methods: Between 2002 and 2009, 270 medial fixed UKAs were performed in our unit. Patients were reviewed pre-operatively, 5 and 8 years post-operatively. Clinical and radiographic reviews were carried out. Patients’ outcome scores (Oxford, WOMAC and American Knee Score) were documented in our database and analysed. Results: Survival and clinical outcome data of 236 knees with a mean 7.3 years follow-up are reported. Every patient with less than 4.93 years follow-up underwent a revision. The patients’ average age at the time of surgery was 69.5 years. The American Knee Society Pain and Function scores, the Oxford Knee Score and the WOMAC score all improved significantly. The 5 years survival rate was 94.1% with implant revision surgery as an end point. The estimated 10 years survival rate is 91.3%. 14 patients were revised before the 5 year follow-up. Conclusion: Fixed bearing Uniglide UKA with an all-polyethylene tibial component is a valuable tool in the management of a medial compartment osteoarthritis, affording good short term survivorship.

CpxR activates MexAB-OprM efflux pump expression and enhances antibiotic resistance in both laboratory and clinical nalB-type isolates of Pseudomonas aeruginosa

Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope stress response in Escherichia coli, is directly involved in activation of expression of RND efflux pump MexAB-OprM in P. aeruginosa. A conserved CpxR binding site was identified upstream of the mexA promoter in all genome-sequenced P. aeruginosa strains. CpxR is required to enhance mexAB-oprM expression and drug resistance, in the absence of repressor MexR, in P. aeruginosa strains PA14. As defective mexR is a genetic trait associated with the clinical emergence of nalB-type multidrug resistance in P. aeruginosa during antibiotic treatment, we investigated the involvement of CpxR in regulating multidrug resistance among resistant isolates generated in the laboratory via antibiotic treatment and collected in clinical settings. CpxR is required to activate expression of mexAB-oprM and enhances drug resistance, in the absence or presence of MexR, in ofloxacin-cefsulodin-resistant isolates generated in the laboratory. Furthermore, CpxR was also important in the mexR-defective clinical isolates. The newly identified regulatory linkage between CpxR and the MexAB-OprM efflux pump highlights the presence of a complex regulatory network modulating multidrug resistance in P. aeruginosa.

Oncology research and clinical decisions based on immunohistochemistry: the importance of the technical aspects that support a complex method

Immunohistochemistry (IHC) is the group of techniques that use antibodies as specific reagents to identify and demonstrate several cell and tissue components that are antigens. This linking allows locating and identifying the in situ presence of various substances by means of color that is associated with the formed antigen-antibody complexes. The practical value of this biotechnology area, widely used in Pathology and Oncology, in diagnostic, prognostic, theranostic and research context, results from the possibility of combining a colour marker with an antibody without causing any damage to specific binding established between antibody and antigen. This provides the microscopic observation of the target locations where the antibody and hence the antigen are present. IHC is presented as a powerful means for identification of several cellular and tissue structures that can be associated with pathologies, and of the consequences, at functional and morphological level, of these same elements action.

New tools for cognitive and motor rehabilitation: development and clinical validation

Nervous system disorders are associated with cognitive and motor deficits, and are responsible for the highest disability rates and global burden of disease. Their recovery paths are vulnerable and dependent on the effective combination of plastic brain tissue properties, with complex, lengthy and expensive neurorehabilitation programs. This work explores two lines of research, envisioning sustainable solutions to improve treatment of cognitive and motor deficits. Both projects were developed in parallel and shared a new sensible approach, where low-cost technologies were integrated with common clinical operative procedures. The aim was to achieve more intensive treatments under specialized monitoring, improve clinical decision-making and increase access to healthcare. The first project (articles I – III) concerned the development and evaluation of a web-based cognitive training platform (COGWEB), suitable for intensive use, either at home or at institutions, and across a wide spectrum of ages and diseases that impair cognitive functioning. It was tested for usability in a memory clinic setting and implemented in a collaborative network, comprising 41 centers and 60 professionals. An adherence and intensity study revealed a compliance of 82.8% at six months and an average of six hours/week of continued online cognitive training activities. The second project (articles IV – VI) was designed to create and validate an intelligent rehabilitation device to administer proprioceptive stimuli on the hemiparetic side of stroke patients while performing ambulatory movement characterization (SWORD). Targeted vibratory stimulation was found to be well tolerated and an automatic motor characterization system retrieved results comparable to the first items of the Wolf Motor Function Test. The global system was tested in a randomized placebo controlled trial to assess its impact on a common motor rehabilitation task in a relevant clinical environment (early post-stroke). The number of correct movements on a hand-to-mouth task was increased by an average of 7.2/minute while the probability to perform an error decreased from 1:3 to 1:9. Neurorehabilitation and neuroplasticity are shifting to more neuroscience driven approaches. Simultaneously, their final utility for patients and society is largely dependent on the development of more effective technologies that facilitate the dissemination of knowledge produced during the process. The results attained through this work represent a step forward in that direction. Their impact on the quality of rehabilitation services and public health is discussed according to clinical, technological and organizational perspectives. Such a process of thinking and oriented speculation has led to the debate of subsequent hypotheses, already being explored in novel research paths.

Finnish Preclinical and Clinical Medical Students as Strategic L2 English Learners: Language Learning Strategies and Communicating with Patients

This thesis focused on medical students’ language learning strategies for patient encounters. The research questions concerned the types of learning strategies that medical students use and the differences between the preclinical students and the clinical students, two groups who have had varying amounts of experience with patients. Additionally, strategy use was examined through activity systems to gain information on the context of language learning strategy use in order to learn language for patient encounters. In total, 130 first-year medical students (preclinical) and 39 fifth-year medical students (clinical) participated in the study by filling in a questionnaire on language learning strategies. In addition, two students were interviewed in order to create activity systems for the medical students at different stages of their studies. The study utilised both quantitative and qualitative research methods; the analysis of the results relies on Oxford’s Strategic Self-Regulation Model in the quantitative part and on activity theory in the qualitative part. The theoretical sections of the study introduced earlier research and theories regarding English for specific purposes, language learning strategies and activity theory. The results indicated that the medical students use affective, sociocultural-interactive and metasociocultural-interactive strategies often and avoid using negative strategies, which hinder language learning or cease communication altogether. Slight differences between the preclinical and clinical students were found, as clinical students appear to use affective and metasociocultural-interactive strategies more frequently compared to the preclinical students. The activity systems of the two students interviewed were rather similar. The students were at different stages of their studies, but their opinions were very similar. Both reported the object of learning to be mutual understanding between the patient and the doctor, which in part explains the preference for strategies that support communication and interaction. The results indicate that the nature of patient encounters affects the strategy use of the medical students at least to some extent.

Terapias antimicrobianas en infecciones odontogénicas en niños y adolescentes. Revisión de la literatura y recomendaciones para la clínica: Literature review and clinical recomendations

Las infecciones bucales son producidas por un desequilibrio de la flora indígena del paciente que pasa de comensal a oportunista. Las consultas más frecuentes en niños y adolescentes son las infecciones odontogénicas. El uso racional de antibióticos, es la estrategia más importante para evitar la resistencia microbiana. Las infecciones dentarias deben recibir en primera instancia el tratamiento local correspondiente y a veces complementarse con tratamiento sistémico seleccionando y dosificando adecuadamente el fármaco. El antimicrobiano de primera elección en odontopediatría es la amoxicilina y para pacientes con hipersensibilidad a las penicilinas, se indican claritromicina o clindamicina. Esta revisión de la literatura busca establecer pautas de manejo clínico claras para el tratamiento de urgencia y su posterior resolución definitiva

Molecular and biological characterisation of orthobunyaviruses

Orthobunyaviruses are the largest genus within the Bunyaviridae family, with over 170 named viruses classified into 18 serogroups (Elliott and Blakqori, 2001; Plyusnin et al., 2012). Orthobunyaviruses are transmitted by arthropods and have a tripartite negative sense RNA genome, which encodes 4 structural proteins and 2 non-structural proteins. The non-structural protein NSs is the primary virulence factor of orthobunyaviruses and potent antagonist of the type I interferon (IFN) response. However, sequencing studies have identified pathogenic viruses that lack the NSs protein (Mohamed et al., 2009; Gauci et al., 2010). The work presented in this thesis describes the molecular and biological characterisation of divergent orthobunyaviruses. Data on plaque morphology, growth kinetics, protein profiles, sensitivity to IFN and activation of the type I IFN system are presented for viruses in the Anopheles A, Anopheles B, Capim, Gamboa, Guama, Minatitlan, Nyando, Tete and Turlock serogroups. These are complemented with complete genome sequencing and phylogenetic analysis. Low activation of IFN by Tete serogroup viruses, which naturally lack an NSs protein, was also further investigated by the development of a reverse genetics system for Batama virus (BMAV). Recombinant viruses with mutations in the virus nucleocapsid protein amino terminus showed higher activation of type I IFN in vitro and data suggests that low levels of IFN are due to lower activation rather than active antagonism. The anti-orthobunyavirus activity of IFN-stimulated genes IFI44, IFITMs and human and ovine BST2 were also studied, revealing that activity varies not only within the orthobunyavirus genus and virus serogroups but also within virus species. Furthermore, there was evidence of active antagonism of the type I IFN response and ISGs by non-NSs viruses. In summary, the results show that pathogenicity in man and antagonism of the type I IFN response in vitro cannot be predicted by the presence, or absence, of an NSs ORF. They also highlight problems in orthobunyavirus classification with discordance between classical antigen based data and phylogenetic analysis.

Formation of seep carbonates along the makran convergent margin, northern Arabian sea and a molecular and isotopic approach to constrain the carbon isotopic composition of parent methane

Authigenic carbonate deposits have been sampled with the remotely operated vehicle ‘MARUM-QUEST 4000 m’ from five methane seeps between 731 and 1823 m water depth along the convergent Makran continental margin, offshore Pakistan (northern Arabian Sea). Two seeps on the upper slope are located within the oxygen minimum zone (OMZ; ca. 100 to 1100 m water depth), the other sites are situated in oxygenated water below the OMZ (below 1100 m water depth). The carbonate deposits vary with regard to their spatial extent, sedimentary fabrics, and associated seep fauna: Within the OMZ, carbonates are spatially restricted and associated with microbial mats, whereas in the oxygenated zone below the OMZ extensive carbonate crusts are exposed on the seafloor with abundant metazoans (bathymodiolin mussels, tube worms, galatheid crabs). Aragonite and Mg-calcite are the dominant carbonate minerals, forming common early diagenetic microcrystalline cement and clotted to radial-fibrous cement. The δ18Ocarbonate values range from 1.3 to 4.2‰ V-PDB, indicating carbonate precipitation at ambient bottom-water temperature in shallow sediment depth. Extremely low δ13Ccarbonate values (as low − 54.6‰ V-PDB) point to anaerobic oxidation of methane (AOM) as trigger for carbonate precipitation, with biogenic methane as dominant carbon source. Prevalence of biogenic methane in the seepage gas is corroborated by δ13Cmethane values ranging from − 70.3 to − 66.7‰ V-PDB, and also by back-calculations considering δ13Cmethane values of carbonate and incorporated lipid biomarkers. These calculations (Δδ13Cmethane–carbonate, Δδ13CANME–methane, Δδ13CMOX–methane) prove to be useful to assess the carbon stable isotope composition of seeping methane if this has not been determined in the first place; such an approach represents a useful tool to reconstruct fluid composition of ancient seeps. AOM is also revealed by lipid biomarkers of anaerobic methane oxidizing archaea such as crocetane, pentamethylicosane (PMI), and sn2-hydroxyarchaeol strongly depleted in 13C (δ13C values as low as − 127‰ V-PDB). Biomarkers of sulphate-reducing bacteria are also abundant, showing slightly less negative δ13C values, but still significantly 13C-depleted (average values as low as − 101‰). Other bacterial biomarkers, such as bacteriohopanepolyols (BHPs), hopanols, and hopanoic acids are detected in most carbonates, but are particularly common in seep carbonates from the non-OMZ sites. The BHP patterns of these carbonates and their low δ13C values resemble patterns of aerobic methanotrophic bacteria. In the shallower OMZ sites, BHPs revealed much lower contents and varying compositions, most likely reflecting other sources than aerobic methanotrophic bacteria. 230Th/U carbonate ages indicate that AOM-induced carbonate precipitation at the deeper non-OMZ seeps occurred mainly during the late Pleistocene-Holocene transition, i.e. between 19 and 15 ka before present, when the global sea level was lower than today.