Exploring the Ethical Dimensions of Public Service

Interest in ethical issues faced by government officials dates back at least to Plato’s “Republic,” and ethics can be considered so salient that some public administration scholars have gone as far as to define it as “the most important public policy” (Maletz and Herbel 2000). The three chapters of my dissertation have the overall aim of contributing to our understanding of ethics in public administration and, more specifically, within complex public organizations. To do so, after an exercise of stocktaking and systematization of what we know (Chapter 1), my work investigates critical questions on ethics in the empirical context of healthcare organizations (Chapters 2 and 3). In Chapter 1, I systematically review 160 articles from six top-ranked journals discussing ethics in public administration scholarship, thus illuminating ethical issues and dynamics emerging at different levels of public administration life. Furthermore, I offer a three-pronged classification of ethics in public administration that allows organizing ethical issues at the institutional, managerial, and individual levels. Results suggest that dilemmas and challenges arise from conflicting interests and values inside and between levels. Moreover, this chapter highlights the importance of including a level that has remained fairly overlooked by previous studies, i.e., the managerial level. I posit that recognizing and addressing the ethical dilemmas experienced at the managerial level may have positive spillovers on individuals and communities. Therefore, in the second and third chapters, I explore ethical issues characterizing the decision-making processes of public managers, as well as the strategies through which public managers pursue their core mandate in contexts replete with dilemmas. In Chapter 2, I explore the ethical dilemmas experienced in decision-making processes by public health managers when confronted with trade-offs between individual patients’ interests and the community interest in public health. Through a sequential mixed methods design, the chapter aims at understanding how healthcare managers perceive such ethical dilemmas and the relative importance of different factors influencing their preferences. Findings show that health managers’ experience of a health emergency is characterized by negative emotions and difficulty balancing their responsibilities as clinicians and their duties as managers. Chapter 3 explores the implementation of the contentious policy issue of voluntary termination of pregnancy in Italy, characterized by conflicting although legitimate interests. On the one hand, the woman has the legitimate interest to request the interruption of her pregnancy; on the other hand, the legitimate right to conscientiously object to providing this service is granted to gynecologists and other health professionals. Conscientious objection has divisive consequences on the workplace collective. Owing to societal developments such as value pluralism and professionalism, as well as to advancements in biotechnology, this provision is likely to spread across policy domains and countries. Yet, little is known about the role of managers in orchestrating the delivery of public services that trigger an ethical division in the workplace, such as elective abortion. This is exactly the focus of this chapter, which builds on studies on conflicting values and ethical dilemmas in public services, as well as on the notion of ‘dirty work.’ Through a qualitative research design based on semi-structured interviews, our findings illuminate strategies through which managers ensure service delivery with a divided workforce by attending to the ethical dilemmas in their discursive, structural, and organizational strategies

Genome-wide expression profiling of the response to short-term exposure to fluconazole in Cryptococcus neoformans serotype A

Fluconazole (FLC), a triazole antifungal drug, is widely used for the maintenance therapy of cryptococcal meningoencephalitis, the most common opportunistic infection in AIDS patients. In this study, we examined changes in the gene expression profile of the C. neoformans reference strain H99 (serotype A) following FLC treatment in order to investigate the adaptive cellular responses to drug stress

The Current State of Validation of Administrative Healthcare Databases in Italy: A Systematic Review

Background: Administrative healthcare databases are widely present in Italy. Our aim was to describe the current state of healthcare databases validity in terms of discharge diagnoses (according to the International Classification of Diseases, ICD-9 code) and their output in terms of research.Methods: A systematic search of electronic databases including Medline and Embase (1995-2013) and of local sources was performed. Inclusion criteria were: healthcare databases in any Italian territory routinely and passively collecting data; medical investigations or procedures at patient level data; the use of a validation process. The quality of studies was evaluated using the STARD criteria. Citations of the included studies were explored using Scopus and Google Scholar.Results: The search strategy allowed the identification of 16 studies of which 3 were in Italian. Thirteen studies used regional administrative databases from Lombardia, Piemonte, Lazio, Friuli-Venezia Giulia and Veneto. The ICD-9 codes of the following diseases were successfully validated: amyotrophic lateral sclerosis (3 studies in four different regional administrative databases), stroke (3 studies), gastrointestinal bleeding (1 study), thrombocytopenia (1 study), epilepsy (1 study), infection (1 study), chronic obstructive pulmonary disease (1 study), Guillain-Barre syndrome (1 study), and cancer diseases (4 studies). The quality of reporting was variable among the studies. Only 6 administrative databases produced further research related to the validated ICD-9 codes.Conclusion: Administrative healthcare databases in Italy need an extensive process of validation for multiple diagnostic codes to perform high quality epidemiological and health services research

Hemoparasitosis en ganadería doble propósito venezolana, diagnóstico y control: una revisión

Este trabajo de revisión de tesis doctoral incluye resultados de investigaciones realizadas en el periodo 1971 a 2009 sobre cuatro hemoparasitosis causados por protozoarios y rickettsiales en Venezuela y otros países, con énfasis en la infección mixta en rebaños bovinos, y su diagnóstico y control. En Venezuela, las afecciones causadas por agentes hemotrópicos parasitarios están distribuidas en todos los estados del país con vocación ganadera, en especial, en rebaños bovinos y bufalinos. Entre aquellos encontramos a especies del género Anaplasma (Anaplasma marginale), Babesia (Babesia bigemina y B. bovis), y Trypanosoma (Trypanosoma vivax), con una frecuencia endémica y con variaciones estacionales

Passive immunotherapy for N-truncated tau ameliorates the cognitive deficits in two mouse Alzheimer's disease models

Abstract Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making tau an attractive target for the cure of Alzheimer's disease. We have explored whether passive immunization with the 12A12 monoclonal antibody (26–36aa of tau protein) could improve the Alzheimer's disease phenotype of two well-established mouse models, Tg2576 and 3xTg mice. 12A12 is a cleavage-specific monoclonal antibody which selectively binds the pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) of tau protein without cross-reacting with its full-length physiological form(s). We found out that intravenous administration of 12A12 monoclonal antibody into symptomatic (6 months old) animals: (i) reaches the hippocampus in its biologically active (antigen-binding competent) form and successfully neutralizes its target; (ii) reduces both pathological tau and amyloid precursor protein/amyloidβ metabolisms involved in early disease-associated synaptic deterioration; (iii) improves episodic-like type of learning/memory skills in hippocampal-based novel object recognition and object place recognition behavioural tasks; (iv) restores the specific up-regulation of the activity-regulated cytoskeleton-associated protein involved in consolidation of experience-dependent synaptic plasticity; (v) relieves the loss of dendritic spine connectivity in pyramidal hippocampal CA1 neurons; (vi) rescues the Alzheimer's disease-related electrophysiological deficits in hippocampal long-term potentiation at the CA3-CA1 synapses; and (vii) mitigates the neuroinflammatory response (reactive gliosis). These findings indicate that the 20–22 kDa NH2-terminal tau fragment is crucial target for Alzheimer's disease therapy and prospect immunotherapy with 12A12 monoclonal antibody as safe (normal tau-preserving), beneficial approach in contrasting the early Amyloidβ-dependent and independent neuropathological and cognitive alterations in affected subjects

Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia

IntroductionFrontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs.MethodsBy the means of a new immunoassay, we have measured and analyzed the proNGF levels in 43 cerebrospinal fluids (CSF) from FTD patients, and compared the results to those obtained in CSF from 84 Alzheimer’s disease (AD), 15 subjective memory complaints (SMC) and 13 control subjects.ResultsA statistically significant difference between proNGF levels in FTD compared to AD, SMC and controls subjects was found. The statistical models reveal that proNGF determination increases the accuracy of FTD diagnosis, if added to the clinically validated CSF biomarkers.DiscussionThese results suggest that proNGF could be included in a panel of biomarkers to improve the FTD diagnosis

Serine Hydroxymethyltransferase from the Cold Adapted Microorganism Psychromonas ingrahamii: A Low Temperature Active Enzyme with Broad Substrate Specificity

Serine hydroxymethyltransferase from the psychrophilic microorganism Psychromonas ingrahamii was expressed in Escherichia coli and purified as a His-tag fusion protein. The enzyme was characterized with respect to its spectroscopic, catalytic, and thermodynamic properties. The properties of the psychrophilic enzyme have been contrasted with the characteristics of the homologous counterpart from E. coli, which has been structurally and functionally characterized in depth and with which it shares 75% sequence identity. Spectroscopic measures confirmed that the psychrophilic enzyme displays structural properties almost identical to those of the mesophilic counterpart. At variance, the P. ingrahamii enzyme showed decreased thermostability and high specific activity at low temperature, both of which are typical features of cold adapted enzymes. Furthermore, it was a more efficient biocatalyst compared to E. coli serine hydroxymethyltransferase (SHMT) particularly for side reactions. Many β-hydroxy-α-amino acids are SHMT substrates and represent important compounds in the synthesis of pharmaceuticals, agrochemicals and food additives. Thanks to these attractive properties, this enzyme could have a significant potential for biotechnological applications

Cladribine and ocrelizumab induce differential miRNA profiles in peripheral blood mononucleated cells from relapsing–remitting multiple sclerosis patients

Background and objectivesMultiple sclerosis (MS) is a chronic, progressive neurological disease characterized by early-stage neuroinflammation, neurodegeneration, and demyelination that involves a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. Even though several disease-modifying therapies (DMTs) are available to prevent MS-related brain damage—acting on the peripheral immune system with an indirect effect on MS lesions—individualizing therapy according to disease characteristics and prognostic factors is still an unmet need. Given that deregulated miRNAs have been proposed as diagnostic tools in neurodegenerative/neuroinflammatory diseases such as MS, we aimed to explore miRNA profiles as potential classifiers of the relapsing–remitting MS (RRMS) patients’ prospects to gain a more effective DMT choice and achieve a preferential drug response.MethodsA total of 25 adult patients with RRMS were enrolled in a cohort study, according to the latest McDonald criteria before (pre-cladribine, pre-CLA; pre-ocrelizumab, pre-OCRE, time T0) and after high-efficacy DMTs, time T1, 6 months post-CLA (n = 10, 7 F and 3 M, age 39.0 ± 7.5) or post-OCRE (n = 15, 10 F and 5 M, age 40.5 ± 10.4) treatment. A total of 15 age- and sex-matched healthy control subjects (9 F and 6 M, age 36.3 ± 3.0) were also selected. By using Agilent microarrays, we analyzed miRNA profiles from peripheral blood mononuclear cells (PBMC). miRNA–target networks were obtained by miRTargetLink, and Pearson’s correlation served to estimate the association between miRNAs and outcome clinical features.ResultsFirst, the miRNA profiles of pre-CLA or pre-OCRE RRMS patients compared to healthy controls identified modulated miRNA patterns (40 and seven miRNAs, respectively). A direct comparison of the two pre-treatment groups at T0 and T1 revealed more pro-inflammatory patterns in the pre-CLA miRNA profiles. Moreover, both DMTs emerged as being capable of reverting some dysregulated miRNAs toward a protective phenotype. Both drug-dependent miRNA profiles and specific miRNAs, such as miR-199a-3p, miR-29b-3p, and miR-151a-3p, emerged as potentially involved in these drug-induced mechanisms. This enabled the selection of miRNAs correlated to clinical features and the related miRNA–mRNA network.DiscussionThese data support the hypothesis of specific deregulated miRNAs as putative biomarkers in RRMS patients’ stratification and DMT drug response

Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist

Objectives: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). Methods: The writing committee selected the HRCT criteria\ue2\u80\u94the Delphi items\ue2\u80\u94for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as \ue2\u80\u9cessential\ue2\u80\u9d, \ue2\u80\u9coptional\ue2\u80\u9d, or \ue2\u80\u9cnot relevant\ue2\u80\u9d. The items rated \ue2\u80\u9cessential\ue2\u80\u9d by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. Results: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated \ue2\u80\u9cessential\ue2\u80\u9d by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated \ue2\u80\u9cessential\ue2\u80\u9d by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. Conclusions: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage