A Literature Systematic Review with Meta-Analysis of Symptoms Prevalence in Covid-19: the Relevance of Olfactory Symptoms in Infection Not Requiring Hospitalization.

PURPOSE OF REVIEW: To investigate the association between the olfactory dysfunction and the more typical symptoms (fever, cough, dyspnoea) within the Sars-CoV-2 infection (COVID-19) in hospitalized and non-hospitalized patients. RECENT FINDINGS: PubMed, Scopus and Web of Science databases were reviewed from May 5, 2020, to June 1, 2020. Inclusion criteria included English, French, German, Spanish or Italian language studies containing original data related to COVID19, anosmia, fever, cough, and dyspnoea, in both hospital and non-hospital settings. Two investigators independently reviewed all manuscripts and performed quality assessment and quantitative meta-analysis using validated tools. A third author arbitrated full-text disagreements. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 of 135 studies fulfilled eligibility. Anosmia was estimated less prevalent than fever and cough (respectively rate difference = - 0.316, 95% CI: - 0.574 to - 0.058, Z = - 2.404, p < 0.016, k = 11 and rate difference = - 0.249, 95% CI: - 0.402 to - 0.096, Z = - 3.185, p < 0.001, k = 11); the analysis between anosmia and dyspnoea was not significant (rate difference = - 0.008, 95% CI: - 0.166 to 0.150, Z = - 0.099, p < 0.921, k = 8). The typical symptoms were significantly more frequent than anosmia in hospitalized more critical patients than in non-hospitalized ones (respectively [Q(1) = 50.638 p < 0.000, Q(1) = 52.520 p < 0.000, Q(1) = 100.734 p < 0.000). SUMMARY: Patient with new onset olfactory dysfunction should be investigated for COVID-19. Anosmia is more frequent in non-hospitalized COVID-19 patients than in hospitalized ones.

Enhancing adherence to antipsychotic treatment for bipolar disorders. Comparison of mobile app-based psychoeducation, group psychoeducation, and the combination of both: protocol of a three-arm single-blinded parallel-group multi-centre randomised trial.

Group Psychoeducation (PE) is an effective strategy to enhance adherence to antipsychotic treatment in Bipolar Disorders (BD). However, it requires attendance to weekly sessions during a period of about 6 months. This may impede its application for those patients living far from mental health centres, resulting inequality in access to evidence-based care. Therefore, there is an increasing need to find new efficient strategies to deliver and extend PE programs to a wider population of BD patients. Mobile apps are a cost-effective way to deliver PE. In the Italian healthcare context, no evidence about the use of apps is available. The current paper presents the protocol about the development of a smartphone app to deliver PE for BD and the protocol for a trial assessing its effectiveness. In euthymic BD patients, the study will compare the adherence rates to antipsychotics between PE delivered through Bipolar mobile Application (Bip.App), group PE and a combination of both, will investigate demographic, socio-cultural and clinical predictors of lower adherence in the arms, and will investigate whether PE combined with Bip.App is associated with lower risk of recurrence of (hypo)manic and depressive episodes than group PE alone, and assess the feasibility and satisfaction for Bip.App. Participants will be recruited from mental health centres and included if they are 18-65 year-old, have primary BD in the euthymic phase, they have been prescribed a second-generation oral antipsychotic as a maintenance/prophylactic therapy for at least 1 year, they have not undergone a structured protocol of PE for BD, they have access to a smartphone and sufficient competence in using it. Participants will be excluded if they have neurological disease, mental retardation or learning disability, psychosis, limited fluency in Italian. Adherence will be assessed through count pills, blood levels, and self-reported adherence. A single-blinded parallel-group superiority multi-centre randomised controlled trial design will be used.

Clinical risk management in High-Security Forensic Psychiatry Residences. Protecting patients and health professionals: perspectives and critical issues of the Law 81/2014.

The Italian Law n. 9/2012 provided the Italian Regions with a new decisional role by demanding the management/rehabilitation of prisoners judged as partially/fully mentally ill to care and protection delivered by the psychiatric services of the Regional Health Service. Healthcare has to be guaranteed by the so-called High-Security Forensic Psychiatry Residences (Italian: Residenze per l'Esecuzione delle Misure di Sicurezza: REMS) and by community mental health centres. Ensuring patients' and professionals' health and safety is a complex issue which requires effective strategies to cope with several structural, technological, and organisational problems. The present paper summarises the historical evolution of the Italian laws towards the development of the High-Security Forensic Psychiatry Residences in Italy, focusing specifically on the Tuscany Region situation. The paper also presents the key issues emerging after the implementation of the Law 81/2014 which complemented the Law 9/2012. Since these reforms included the need for assessing to what extent the patient may be considered as a danger to society and for ensuring the safety of National Health Service (NHS) professionals, they underscored the importance of a preventive use of specific clinical governance tools aimed to reduce risk of adverse events. The present work has the strength of proposing a new, evidence-based scientific approach to the implementation of assessment and care pathways in High-Security Forensic Psychiatry Residences.

The Workplace Health Promotion (WHP) programme in an Italian University Hospital.

INTRODUCTION: Description of the lifestyles of employees of the Siena University Hospital (Azienda Ospedaliera Universitaria Senese: AOUS), as assessed through a Workplace Health Promotion (WHP) project in the two-year period 2017-18; assessment of possible short-term effects of integrated health promotion interventions in the workplace, within the framework of the Tuscany WHP network, as applied in the AOUS and involving about 1,000 workers. METHODS: A cross-sectional study and a pre-post evaluation of data collected by means of anonymous questionnaires in two phases: before the beginning of the programme and after 12 months. RESULTS: Twelve months after the start of the programme regarding diet (consumption of fruit and vegetables) and physical activity, the positive effects that emerged were not statistically significant. No differences were observed between gender or professional categories. The employees' perception of the programme was satisfactory. CONCLUSIONS: Albeit within the methodological limits of the assessment, the results showed that the diffusion of some major risk factors for chronic diseases had not decreased after 12 months' exposure to the programme. However, monitoring of these risk factors needs to be continued over a longer period, in order to detect the appearance of the expected changes in the long term. Moreover, it is essential to continue monitoring by sex and professional category, in order to pick out any differences and, if possible, take remedial actions. Further studies, in collaboration with the pertinent physicians, are desirable, since integrating data collected during health surveillance with a limited set of indicators of general risk factors may help to promptly identify possible health needs among employees.

Targeting the multidrug ABCG2 transporter with flavonoidic inhibitors: in vitro optimization and in vivo validation.

This review describes the breast cancer resistance protein ABCG2 through its structure, functional roles and involvement in cell multidrug resistance, especially in cancer cells resistance to chemotherapeutics. The different types of known inhibitors are described, some being non-selective, since they also bind to other targets, and others being quite specific such as flavonoids. The different classes of active flavonoids and other polyphenols are described, some as plant natural compounds, but most of them being prepared and derivatized through medicinal chemistry. Quantitative structure-activity relationships of the ability of flavones, chalcones, xanthones, acridones and various benzopyrane/benzofurane derivatives to inhibit ABCG2-mediated drug efflux have led to pharmacophores and molecular models allowing to optimize the available hit compounds and to design new-generation lead compounds. Interestingly, inhibitory flavonoids are quite specific for ABCG2 versus ABCB1 and ABCC1, and appear either non-competitive or partially competitive towards mitoxantrone efflux. Most compounds do not inhibit ATPase activity, and are assumed not to be transported themselves by the transporter. Some acridones, firstly optimized in vitro as potent inhibitors, are indeed efficient in vivo, against human xenografts in SCID mice, more efficiently than gefitinib taken as a control. Future developments should open the way to more efficient/targeted modulators including (i) the potential interest of bimodulation by combining two different inhibitors, (ii) computer-assisted ligand-based drug design for getting more potent and more specific inhibitors, (iii) structure-based drug design from ABCG2 molecular models allowing in silico screening and docking of new inhibitors.

Efeito do silício na intensidade da cercosporiose e na nutrição mineral de mudas de cafeeiro / Effect of silicon on the intensity of brown eye spot and on the mineral nutrition of coffee seedlings

O presente trabalho objetivou estudar o efeito do silício na intensidade da cercosporiose e na nutrição mineral de mudas de cafeeiro. No experimento 1, testou-se seis doses de ácido silícico (0, 0,5; 1; 2; 4 e 6 g kg­1 de solo) em mudas da cultivar Catuaí Vermelho IAC 99 inoculadas com o fungo Cercospora coffeicola. No experimento 2, foram realizadas microanálises de raios-X para a avaliação de nutrientes presentes nas folhas das mudas de cafeeiro das cultivares Topázio MG1190 e Icatu Precoce IAC 3282, inoculadas e não inoculadas com C. coffeicola, com e sem silicato de cálcio (1 g kg-1 de solo). Com o aumento das doses de ácido silícico observou-se redução na área abaixo da curva de progresso do número de lesões por folha (AACPNLF), redução linear nos teores foliares de magnésio e fósforo e aumento nos teores de enxofre e cobre. Os teores foliares de boro apresentaram comportamento quadrático, diminuindo com o aumento das doses de ácido silícico e aumentando a partir da dose de 4 g kg-1 de solo. Em microanálise de raio X, mudas de cafeeiro com cercosporiose apresentam menores picos de potássio e cálcio, independente da cultivar utilizada.

Our objective was to verify the effect of silicon on the intensity of brown eye spot and on the mineral nutrition of coffee seedlings. In the first experiment, 6 doses of silicic acid (0, 0.5, 1, 2, 4 and 6 g kg-1 soil) were tested using a complete randomized block design with 4 replicates with 6 coffee seedlings cultivar Catuaí Vermelho IAC 99 inoculated with the fungus Cercospora coffeicola. In the second experiment, X-ray microanalysis in a scanning electron microscope was performed on 2 coffee cultivars (Topazio MG1190 and Icatu Precoce IAC 3282), inoculated and non-inoculated with C. coffeicola, treated and untreated with calcium silicate (1 g kg-1 of soil). With the increase of the silicic acid doses, there was observed a reduction in the area under the disease progress curve of the number of lesions per leaf (AUPCNLL), coupled with a linear reduction in the foliar contents of magnesium and phosphorus as well as an increase in the contents of sulfur and copper. The foliar contents of boron presented a quadratic behavior, decreasing with the increase of silicic acid and increasing with the dose of 4 g kg-1 of soil. In X-ray microanalysis, coffee seedlings with brown eye spot presented lower peaks of potassium and calcium, regardless of the cultivar used.

Diverting loop ileostomy after restorative proctocolectomy: predictors of poor outcome and poor quality of life.

AIM: Diverting loop ileostomy is used to minimize the impact of anastomotic complication after restorative proctocolectomy (RPC). However, the ileostomy itself may have complications and therefore affect quality of life (QOL). The aim of this study was to analyse the predictors of complications of the ileostomy formation and closure and of the QOL of these patients. METHOD: Forty-four consecutive patients who underwent RPC were enrolled. Records of the ileostomy follow-up were retrieved from a prospectively collected database and QOL was assessed with the Stoma-QOL questionnaire. Ileostomy site coordinates were measured. Univariate and multivariate analysis were performed. RESULTS: In this series, three patients experienced peristomal herniae, two ileostomy stenosis, seven ileostomy retraction and fourteen peristomal dermatitis. Emergency surgery was the only predictor of parastomal hernia (P = 0.017). Stenosis correlated with the distance from the umbilicus (tau = 0.24, P = 0.021). Use of standard rod and retraction were independent predictors of peristomal dermatitis (P = 0.049 and P = 0.001). Stoma-QOL was directly correlated to the age of the patients and to the occurrence of parastomal hernia (P = 0.001 and P = 0.021, respectively). After stoma closure, two patients reported wound sepsis and seven suffered obstructive episodes. CONCLUSION: The predictors of negative outcome after construction of a diverting loop ileostomy after RPC were urgent surgery, use of standard rod, the distance of the stoma site from the umbilicus, parastomal herniae and the older age of patients.

Cardiovascular autonomic function in Cushing's syndrome.

Cardiac autonomic dysfunction is associated with increased cardiovascular mortality. No data on sympathovagal balance are available in patients with Cushing's syndrome, in whom cardiovascular risk is high. We studied 10 patients with newly diagnosed Cushing's syndrome (1 male/9 females; age mean+/-SD, 47+/-10 yr) and 10 control subjects matched for age, sex, body mass index, and cardiovascular risk factors. In both groups there were 7 patients with arterial hypertension, 3 with diabetes mellitus, and 2 with obesity. Cardiac autonomic function was evaluated by analysis of short time heart rate variability (HRV) measures in frequency domain over 24-h, daytime, and nighttime. The 24-h ambulatory blood pressure monitoring and echocardiography were also performed. In comparison with controls, patients with Cushing's syndrome had lower 24-h (1.3+/-0.6 vs 3.7+/-1.5, mean+/-SD, p<0.01), daytime (2.0+/-1.4 vs 4.5+/-1.6, p<0.01), and night-time (1.0+/-0.4 vs 3.5+/-2.3, p<0.01) low-frequency/ high frequency (LF/HF) power ratio. In the presence of similar LF power, the difference was due to elevation in HF power in Cushing's syndrome compared to controls: 24-h, 12.7+/-6.7 vs 5.8+/-2.8, p<0.01; daytime, 10.2+/-7.3 vs 4.5+/-2.1, p<0.05; nighttime, 14.2+/-7.0 vs 7.8+/-4.7, p<0.05. Eight Cushing patients vs 4 controls had a non-dipping blood pressure profile. At echocardiography, Cushing patients had a greater left ventricular mass index and/or relative wall thickness, and impaired diastolic function, compared with controls. Compared to controls, patients with Cushing's syndrome showed a sympathovagal imbalance, characterized by a relatively increased parasympathetic activity. Whether this autonomic alteration is meant to counterbalance cortisol-induced effects on blood pressure and cardiac structure/function or has a different pathophysiological significance is still unknown.

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension.

BACKGROUND AND AIM: Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. METHODS AND RESULTS: The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. CONCLUSIONS: Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

Purification of breast cancer resistance protein ABCG2 and role of arginine-482.

Human ABCG2 was efficiently overexpressed in insect cell membranes, solubilized with 3-[(3-cholamidopropyl)dimethyl ammonio]-1-propanesulfonate, and purified through N-terminal hexahistidine tag. Its functionality was assessed by high vanadate-sensitive ATPase activity, and nucleotide-binding capacity. Interestingly, the R482T point mutation increased both maximal hydrolysis rate and affinity for MgATP, and lowered sensitivity to vanadate inhibition. Direct nucleotide binding, as monitored by quenching of intrinsic fluorescence, indicated a mutation-related preference for ATP over ADP. The R482T mutation only produced a limited change, if any, on the binding of drug substrates, indicating that methotrexate, on the one hand, and rhodamine 123 or doxorubicin, on the other hand, bound similarly to wild-type and mutant transporters whether or not they were subject to cellular transport. In addition, the characteristic inhibitors GF120918 and 6-prenylchrysin, which alter mitoxantrone efflux much better for wild-type than mutant ABCG2, bound similarly to purified ABCG2, while the highly-potent Ko143 bound in the nanomolar range also effective in inhibition of drug transport. All results indicate that the role of the arginine-482 mutation on substrate drug transport and inhibitor efficiency is not mediated by changes in drug binding.

Further lowering of muscle lipid oxidative capacity in obese subjects after biliopancreatic diversion.

A reduced lipid oxidative capacity is considered a risk factor for the development of obesity, but a further impairment of lipid oxidative capacity is observed after weight loss. We aimed to define the mechanisms underlying this phenomenon in skeletal muscle and in particular to study the mitochondrial and peroxisomal lipid oxidative pathways. Thus we measured intramyocellular triglyceride content (IMTG) and the expression of genes of lipid oxidation [peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase 1B, and acyl-coenzyme A (acyl-CoA) oxidase 1] and synthesis (acetyl-CoA carboxylase B) using RT-PCR analysis in muscle biopsies of morbidly obese patients before and after biliopancreatic diversion. Weight reduction significantly decreased IMTG while increasing insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Moreover, an increase in glucose and a decline in lipid oxidation, as assessed by respiratory chamber, were observed. Weight loss reduced the expression of peroxisome proliferator-activated receptor-alpha (-46.7%), carnitine palmitoyltransferase 1B (-43.1%), acyl-CoA oxidase 1 (-37.8%), and acetyl-CoA carboxylase B (-48.7%). Our results indicate that a defect of both peroxisomal and mitochondrial oxidative pathways at the muscular level may contribute to the reduced fat oxidation in obese subjects after biliopancreatic diversion. They also suggest that a depression of the de novo lipogenesis may account for IMTG depletion.