Foveal avascular zone area and parafoveal vessel density measurements in different stages of diabetic retinopathy by optical coherence tomography angiography

AIM：To investigate foveal avascular zone（FAZ）and parafoveal vessel densities（PRVD）by means of optical coherence tomography angiography（OCTA）in diabetic patients with or without diabetic retinopathy（DR）and to assess the reproducibility of FAZ and PRVD measurements.METHODS：Sixty diabetic patients（60 eyes）with different stage of DR（graded according to the International Clinical Severity Scale for DR）and 20 healthy subjects underwent FAZ area and PRVD measurements using OCTA by two experienced examiners.FAZ area in all patients was also assessed using fluorescein angiography（FA）.RESULTS：In subject with proliferative DR and with moderate-severe non proliferative DR,FAZ area was significantly increased compared to healthy controls（P=0.025 and P=0.050 respectively measured with OCTA and P=0.025 and P=0.048 respectively measured with FA）.OCTA showed significantly less inter-observer variability compared to FA.Concordance correlation coefficient（CCC）for FAZ area measurements was 0.829（95%CI：0.736-0.891）P〈0.001 with FA and 1.000（95%CI：0.999-1.000）P〈0.001with OCTA.CCC was 0.834（95%CI：0.746-0.893）P〈0.001and 0.890（95%CI：0.828-0.930）P〈0.001 for parafoveal superficial and deep vessel density measurements,respectively.CONCLUSION：OCTA shows progressive increase of FAZ area and reduction of PRVD in both superficial and deep plexus at increasing DR severity.FAZ area and PRVD measurements using OCTA are highly reproducible.

Targeting neuronal nitric oxide synthase as a valuable strategy for the therapy of neurological disorders

The management of neurological disorders have huge and increasing human and economic costs. Despite this, there is a scarcity of effective therapeutics, and there is an extreme urgency for new and real treatments. In this short review we analyze some promising advancements in the search of new bioactive molecules targeting neuronal nitric oxide synthase （nNOS）, an enzyme deputed to the biosynthesis of nitric oxide （NO）. In different conditions of neuronal damages, this molecule is overproduced, contributing to the pathogenesis and progression of neuronal diseases. Two main approaches to modulate nNOS are discussed： a first one consisting in the direct inhibition of the enzyme by means of small organic molecules, which can be also active against other different targets involved in such diseases. A second section is dedicated to molecules able to prevent the formation of the ternary complex N-methyl-D-aspartate （NMDA）type glutamate receptors, postsynaptic density-95 （PSD95） protein-nNOS, which is necessary to activate the latter for the biosynthesis of NO.

Role of monoclonal antibody drugs in the treatment of COVID-19

Currently clinicians all around the world are experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The clinical presentation of this pathology includes fever,dry cough,fatigue and acute respiratory distress syndrome that can lead to death infected patients.Current studies on coronavirus disease 2019(COVID-19)continue to highlight the urgent need for an effective therapy.Numerous therapeutic strategies have been used until now but,to date,there is no specific effective treatment for SARS-CoV-2 infection.Elevated inflammatory cytokines have been reported in patients with COVID-19.Evidence suggests that elevated cytokine levels,reflecting a hyperinflammatory response secondary to SARS-CoV-2 infection,are responsible for multi-organ damage in patients with COVID-19.For these reason,numerous randomized clinical trials are currently underway to explore the effectiveness of biopharmaceutical drugs,such as,interleukin-1 blockers,interleukin-6 inhibitors,Janus kinase inhibitors,in COVID-19.The aim of the present paper is to briefly summarize the pathogenetic rationale and the state of the art of therapeutic strategy blocking hyperinflammation.

The Flexible Housing： Criteria and Strategies for Implementation of the Flexibility

The design of housing systems is today challenged by a highly uncertain context, dominated by the rapid development of functional and technological obsolescence in inherited housing models. If flexibility is the ability of a system to be easily modified and to respond to changes in the environment timely and conveniently, it can be considered as the antidote to obsolescence or the characteristic of the system that guarantees slippage over time. Our paper focuses on the concept of flexibility as a fundamental prerequisite for residential building in order to extend its life cycle design, through strategies and constructive solutions that ensure both the convertibility of the space in response to changing usage and the use of building materials that encourage the reversibility and the long-term easy maintenance of the technological choices that have been implemented. Flexibility is examined both from a conceptual point of view, so as to obtain a clear and logical definition that is distinct from related terms, as well as from a practical point of view, by finding ways to incorporate this requirement into the designing of housing.

Vascular changes in age-related macular degeneration

Age-related macular degeneration(AMD)is considered one of the principal causes of vision impairment among older individuals in developed countries.Assuming this,new technologies which may increment insights elucidating the morphological characteristics of this disorder are expected to improve the visual prognosis in AMD.The development of optical coherence tomography angiography(OCTA)has outstandingly extended our knowledge on the AMD pathophysiology.

Craving variations in patients with substance use disorder and gambling during COVID-19 lockdown:The Italian experience

BACKGROUND Following the development of the coronavirus disease-2019(COVID-19)pandemic in Italy,a strict lockdown was imposed from March 9 to May 5,2020.The risks of self-medication through alcohol or psychoactive substance abuse were increased,as well as the tendency to adopt pathological behaviors,such as gambling and internet addiction.AIM To evaluate the impact of the COVID-19 pandemic and associated containment measures on craving in a group of patients suffering from substance use disorder and/or gambling disorder who were in treatment in outpatient units or in residency programs as inpatients.METHODS One hundred and fifty-three patients completed a structured questionnaire evaluating craving and other behaviors using a visual analogue scale(VAS).Forty-one subjects completed a pencil and paper questionnaire during the interview.The clinician provided an online questionnaire to 112 patients who had virtual assessments due to lockdown restrictions.Statistical analyses were performed using Statistica version 8.0.Quantitative parameters are presented as the mean±SD and qualitative parameters as number and percentage per class.The Kolmogorov-Smirnov test was used to check for normality of distributions.Analysis of variance and Duncan post hoc test were employed to analyze differences among subgroup means.The associations between variables were measured using Pearson's correlation.A P value of<0.05 was considered significant.RESULTS The variation in craving between the present and the month before showed VASrelated reductions of craving in 57%,increases in 24%,and no significant change in 19%of the sample.The level of craving was significantly higher(F=4.36;P<0.05)in outpatients(n=97;mean=3.8±3.1)living in their own home during the quarantine compared with inpatients(n=56;mean=2.8±2.8)in residential programs.Craving for tetrahydrocannabinol was the greatest(4.94,P<0.001)among various preferred substances.CONCLUSION The unexpected result of this study may be explained by a perceived lack of availability of substances and gambling areas and/or decreased social pressure on a subject usually excluded and stigmatized,or the acquisition of a new social identity based on feelings of a shared common danger and fate that overshadowed the sense of exclusion and rejection in the abuser.

Legacy of neuropsychiatric symptoms associated with past COVID-19 infection:A cause of concern

Although primarily affecting the respiratory system,growing attention is being paid to the neuropsychiatric consequences of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Acute and sub-acute neuropsychiatric manifestations of coronavirus disease 2019(COVID-19)disease and their mechanisms are better studied and understood currently than they had been when the pandemic began;however,many months or years will be necessary to fully comprehend how significant the consequences of such complications will be.In this editorial,we discuss the possible long-term sequelae of the COVID-19 pandemic,deriving our considerations on experiences drawn from past coronaviruses’outbreaks,such as the SARS and the middle east respiratory syndrome,and from the knowledge of the mechanisms of neurotropism and invasiveness of SARS-CoV-2.Acknowledging the global spread of COVID-19 and the vast number of people affected,to date amounting to many millions,the matter of this pandemic’s neuropsychiatric legacy appears concerning.Public health monitoring strategies and early interventions seem to be necessary to manage the possible emergence of a severe wave of neuropsychiatric distress among the survivors.

Natural Philosophy, Inventions and Religion in the Correspondence between John Locke and Nicolas Toinard （1678-1704）

The paper examines the copious correspondence between the English philosopher John Locke （1632-1704） and the French intellectual Nicolas Toinard （1629-1706）; Locke made the acquaintance of Toinard in Paris in 1677 or early in 1678, and the latter remained his lifelong friend and most assiduous correspondent. An Orl6anais and a devout Catholic, Toinard combined an intense interest in the Scriptures with an enthusiasm for experimental science and inventions of every kind; he introduced Locke to all the French official institutions and to a number of private laboratories. Toinard＇s principal work, Evangeliorum Harmonia Graeco-Latina, was greatly appreciated by Locke for its new method. The paper attempts at exploring the bulk of this correspondence in detail, giving an account of the wide range of topics dealt with in the two hundred letters; it is divided into four paragraphs referring, respectively, to the years 1678-1679, 1679-1681, 1681-1686, and1686-1704. The perspective is diachronic; in some occasions, the focus is on a peculiar topic which is the object of prolonged discussion between the two correspondents. In the conclusion, attention is drawn to the relevance of this correspondence in the context of the 17th century and of Locke＇s philosophical thought.

Against Orthodoxy： Sex, Marriage, and Gender Roles in George Meredith＇s Poems and Novels

George Meredith （1828-1909） is acknowledged as a creator of memorable female characters. Meredith＇s heroines are radically different from the women generally encountered in Victorian fiction. Characteristically, Meredith constructs a type of female character who, in a social context hostile to any break with convention, refuses to conform to the stereotype of the weak, passive, and dependant woman. In accordance with J. S. Mill＇s observations in The Subjection of Women （1869）, Meredith thought that the progress of society could be possible only through female emancipation and admittance of women into public practice. This paper discusses the themes of marital disintegration and ＂conscious adultery＂ that affirm the legitimacy of female pleasure against coercion Thus, the paper will take into consideration the sonnet sequence Modern Love （1862） and one of Meredith＇s most neglected novels, Lord Ormont and His Aminta （1894）, whose heroines are unexpectedly depicted as non-conventional, strong, and proud. A close reading of the texts will reveal the narrative strategies and textual devices through which Meredith exploited a model of womanhood that, by subverting the current ideas on sex, marriage, and gender roles, is able to countermine male ＂egoism＂, the only obstacle to the genuine progress of Victorian society toward real democratization

New Idea Generation and Individual Motivation： A Conceptual Framework

The adoption of specific idea management programs is becoming a strategic asset for organizations, as they are increasingly trying to adopt specific organizational solutions to detect, fertilize, evaluate, and promote new idea generation within and across their boundaries. The centrality of the ideas generation is linked to its vital characteristic of being the main source for new products, services, processes, and drivers of change. This paper copes with the controversial role of the general organizational setting and closely focuses on the rewards mechanisms that could further nurture creativity. By formulating a set of propositions, the paper submits that the understanding of the motivational drivers and the organizational settings is paramount to distill the links between idea generation and incentive structures. This paper aims also to critically analyze and assess the impact of extrinsic and intrinsic motivation on idea generation both at an individual and team level, and develop a framework within which it explores the necessary change to be adopted by firms in managing the idea generation. What is new to the field is the recognition of the impact of the individual locus of control on creative performance. In this vein, the paper sees its ultimate aim in uncovering the dynamics of individual and collective motivation related to creativity, considered as the main source for innovation. The paper concludes that new ideas could be nurtured through the adoption of routine system aligned with the companies＇ human resource management policy.

Diverticular disease of the colon:New perspectives in symptom development and treatment

Diverticular disease of the colon is a common disease worldwide.Although the disease is asymptomatic in about 70-80 % of patients,it represents,at least in Western countries,one of the most important gastrointestinal diseases in terms of direct and indirect health costs.Pathogenesis of the disease is still unknown.However,it is the result of complex interactions between colonic structure,intestinal motility,diet and genetic factors.Whilst efficacious preventive strategies remain to be identified,fibre supplementation in the diet is recommended.Why symptoms develop is still unclear.Results of recent experimental studies on irritable bowel syndrome speculated that low grade inflammation of colonic mucosa,induced by changes in bacterial microflora, could affect the enteric nervous system,which is crucial for normal gut function,thus favouring symptom development. This hypothesis could be extrapolated also for diverticular disease,since bacterial overgrowth is present,at least in a subgroup of patients.These perspectives on symptom development are reviewed and new therapeutic approaches are hypothesized.

Safety of interferon β treatment for chronic HCV hepatitis

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicat einfection and prevent progression of the disease. The treatment has evolved from the use of m-interferon (IFNα) alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjectsare not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety ofIFNβ treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-lb HCV hepatitis unresponsive to IFNα treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNβ and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.

Platelet-rich plasma： combinational treatment modalities for musculoskeletal conditions

Current research on common musculoskeletal problems, including osteoart]cular cona]t]ons, tendinopathies, and muscle injuries, focuses on regenerative translational medicine. Platelet-rich plasma therapies have emerged as a potential approach to enhance tissue repair and regeneration. Platelet-rich plasma application aims to provide supraphysiological concentrations of platelets and optionally leukocytes at injured/pathological tissues mimicking the initial stages of healing. However, the efficacy of platelet-rich plasma is controversial in chronic diseases because patients＇ outcomes show partial improvements. Platelet-rich plasma can be customized to specific conditions by selecting the most appropriate formulation and timing for application or by combining platelet-rich plasma with synergistic or complementary treatments. To achieve this goal, researchers should identify and enhance the main mechanisms of healing. In this review, the interactions between platelet-rich plasma and healing mechanisms were addressed and research opportunities for customized treatment modalities were outlined. The development of combinational platelet-rieh plasma treatments that can be used safely and effectively to manipulate healing mechanisms would be valuable and would provide insights into the processes involved in physiological healing and pathological failure.