Chronic hyperplastic anemia as an independent risk factor for atherosclerotic lesions: a lesson from thalassemia intermedia

Introduction. Cardiovascular involvement represents a well-known complication and the primary cause of mortality, both in transfusion-dependent beta thalassemia major (β-TM) and in transfusion-independent beta thalassemia intermedia (β-TI). In β-TM, heart iron overload is considered the main cause of this complication. This is likely due to poor adherence to iron-chelating therapy, resulting in the inability of the body to efficiently remove iron excess derived from transfused red blood cell breakdown. Different clinical pictures may instead be evoked in cardiovascular involvement occurring in β-TI; however, until now, no factor has emerged as the major one responsible for these complications. 
Design and Methods. In the present study, iron status, and lipid profiles in serum, as well as lipid content in peripheral blood mononuclear cells (PBMCs) were evaluated in 70 adult β-TM and in 22 adult β-TI patients. Ninety-two age-matched blood donors, free from any form of thalassemia, were utilized as controls. The mRNA levels of genes involved in the regulation of iron metabolism, such as interleukine 1 alfa (IL1α), tumor necrosis factor alfa (TNFα), as well as those involved in cholesterol homeostasis, such as acetyl-coenzymeA: cholesterol acyltransferase (ACAT-1), neutral cholesterol ester hydrolase (nCEH), and ATP binding cassette-A (ABCA1), were also evaluated in PBMCs from the above subjects.
Results. In β-TI patients, serum iron, transferrin saturation and erythropoietin levels were higher, while transferrin and hepcidin were lower, compared to both β-TM and controls. Hepcidin and ILα mRNA levels were found to be reduced in β-TI-PBMCs, while those of TNFα were increased. A reduction in total and high density lipoprotein cholesterol (TC and HDL-C) in serum, and an accumulation of neutral lipids (NL), coupled with increased mRNA levels of ACAT-1 and decreased nCEH in PBMCs were also observed in β-TI. 
Conclusions. Since most of the parameters found to be altered in β-TI patients have a key role in the initiation and progression of atherosclerosis, we suggest that cardiovascular complications in these patients may be, at least partially, dependent on the occurrence of premature atherosclerotic lesions. 
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1,2,3-triazolo[4,5-h]quinolines: III: preparation and antimicrobial evaluation of 4-ethyl-4,7-dihydro-1(2)-R-1(2)H triazolo[4,5-h]quinolin-7-one-6-carboxylic acids as anti-infectives of the urinary tract

Some 4-ethyl-1(2)-R-1(2)H-4,7-dihydro-triazolo[4,5-h]-quinolin-7-one-6- carboxylic acids were prepared as novel analogues of oxolinic acid, in order to discover the influence of the annelation position of the triazole ring on the antimicrobial activity that, in some isomers triazolo[4,5-f]quinoline carboxylic acids, is selective against Escherichia coli. Some interesting side reactions in the cyclization of 1(2)-R-1(2)H-benzotriazol-4-yl-aminomethylenemalonate are also described. The biological results indicate that this type of annelation is not profitable for antimicrobial activity

Nuovi derivati chinossalinici inibitori della Diidrofolato Reduttasi (DHFR) e della Timidilato Sintetasi (TS) della <i>Leishmania major</i>: risultati preliminari

L’incidenza delle malattie protozoarie imputate al genere Leishmania è aumentata enormemente con la diffusione dell’AIDS. In particolare la forma viscerale della Leishmaniosi sta emergendo come malattia nuova e sempre più frequente. Oltre gli antimoniali altri farmaci importanti sono le pentammidine e l’amfotericina B. Un approccio abbondantemente esplorato in passato è stato lo sviluppo di farmaci antifolici antiprotozoari che bloccano il ciclo dell’acido folico, che, previa attivazione metabolica di enzimi folato dipendenti, attraverso il trasporto di unità carboniose, è responsabile della sintesi de novo degli acidi nucleici e degli amminoacidi. In questo senso sono stati usati il trimetoprim e la pirimetamina che sono attivi contro i plasmodi e i toxoplasmi, ma non contro le Leishmanie e i tripanosomi. Questi due protozoi appartenenti alla classe dei Kinetoplastidae sono sensibili agli antifolici antitumorali come il metotrexato (MTX), ma sviluppano immediatamente una chemioresistenza in quanto riattivano l’autoproduzione di acido folico mediante una via di salvataggio che impiega l’enzima Pteridina riduttasi, recentemente scoperto, appunto, nelle Leishmanie major e nel tripanosoma cruzi. Sulla base di queste premesse ci è sembrato che le nostre molecole a struttura chinossalinica, analoghe al metotrexato, potessero essere impiegate come inibitori enzimatici di questa famiglia di folato

Psychological aspects of students with learning disabilities in e-environments: a mini review and future research directions

What are the main learning difficulties or advantages encountered by students with learning disabilities within e-environments? As a result of the Covid-19 emergency, e-learning is being increasingly used to support students’ learning processes. A number of countries closed their schools altogether, so face-to-face lessons were and have been replaced by distance lessons. A search of current literature via Scopus, Eric and Google Scholar electronic databases was conducted according to Prisma Guidelines. Other sources of literature were also considered, starting from the references in the full text of the articles consulted. We used the following search keywords: “learning disabilities” combined with the “AND/OR” Boolean operator and “e-learning platforms”, “well-being”, “psychological factors”, “emotional distress”, “self-regulation”. One body of literature highlights the lack of inclusive accessibility standards and a lack of attention to specific tools for addressing neuropsychological syndromes, which causes students to develop high levels of stress/anxiety and emotional distress, in addition to low levels of well-being, self-esteem and self-efficacy. Another area of literature looks at how students can develop high levels of self-regulation and emotional awareness, as well as high levels of inclusion. Results are discussed in terms of the promotion of e-learning that focuses on the psychological well-being of students and teachers use of technological tool

Visual outcome and poor prognostic factors in acute retinal necrosis syndrome

Objective: To evaluate the impact of selected clinical parameters on the mid-/long-term visual outcome of patients with acute retinal necrosis (ARN) Design: A retrospective cohort study Methods: Setting: Two University Hospitals (Parma, Italy; Lausanne, Switzerland). Participants: Thirty-nine non-HIV patients (39 eyes) with ARN, as confirmed by polymerase chain reaction on intraocular samples. The following potential predictors were tested using linear regression models: age, sex, etiology, best-corrected visual acuity (BCVA) on admission, delay between ARN symptom onset and treatment initiation, and surgery (performed or not). Main outcome: BCVA at the final follow up Results: Thirty-nine of 39 non-HIV patients (22 men and 17 women; mean age, 50 years) diagnosed with ARN were enrolled in the study. Etiologies were: varicella-zoster virus in 25 eyes (64%), herpes simplex viruses in the remaining 14 eyes. The average follow-up duration was 19 ± 13 months. All patients had undergone systemic antivirals; surgery was performed in 16 eyes. The mean delay between onset of visual symptoms and antiviral treatment initiation was 15 ± 31 days (range, 1–180 days). The mean BCVA at baseline was 0.83 ± 0.75 logMAR, while the mean final BCVA was 0.75 ± 0.81 logMAR. Both initial BCVA and treatment delay (TD) were significantly correlated with the final BCVA (p &lt; 0.05). Conclusions: Initial BCVA and TD seem to be significant predictors of mid-/long-term visual outcome in non-HIV patients affected by ARN

Aspetti medico-legali e giuridico-deontologici del trattamento sanitario obbligatorio

Health treatments usually need a consenting patient but in cases as infective diseases, industrial accidents or mental diseases physicians can apply to MT (Mandatory Treatment). In Italy the first laws concerning obligatory treatment of psychiatric diseases date back to the beginning of 20th century and have been recently modified to have more guarantees of patient’s life and health. In order to allow a MT we need 3 conditions: an emergency situation caused by a health diseases, a non-consenting patient, impossibility to begin an adequate therapy outside hospitals. Any physician can “suggest” a MT to his patient describing briefly the disease and his clinical conditions. The “proposal” must be sent to the Mayor and has to be approved by another doctor working in the ASL (local public health unit). Then the Mayor has 48 hours to send everything to a judge who will validate or not the MT. Health treatment is carried out by Police. MT cannot last longer than 7 days

Detection on OAR7 of QTL affecting fat and protein yields in dairy sheep

The objective of this paper was identifying QTL that affect fat and protein yields in dairy sheep independently of milk yield. Data were collected in an experimental flock of 887 ewes organized in a daughter design. QTL detection focused on OAR7 where 13 microsatellites were available. The genetic abilities to produce fat and protein independently from the ability to produce milk were estimated as the residuals of the regression of EBV for fat and protein yields on EBV for milk yield. One QTL affecting fat yield (CWP=0.00009) and one QTL affecting protein yield (CWP=0.006) were detected. The most probable QTL location was 115.3 cM in the Sheep Best Position Linkage Map Version 4.7 for both traits. No QTL affecting milk yield was detected. The analysis of fat and protein yields independently of milk yield is an effective strategy to identify chromosomal regions affecting milk composition with no detrimental effect on milk yield

Design, synthesis and antitubercular activity of 4-alkoxy-triazoloquinolones able to inhibit the M.\ua0tuberculosis DNA gyrase

A number of new F-triazolequinolones (FTQs) and alkoxy-triazolequinolones (ATQs) were designed, synthesized and evaluated for their activity against Mycobacterium tuberculosis H37Rv. Five out of 21 compounds exhibited interesting minimum inhibitory concentration (MIC) values (6.6-57.9 microM), ATQs generally being more potent than FTQs. Two ATQs, 21a and 30a, were endowed with the best anti-Mtb potency (MIC = 6.9 and 6.6 microM, respectively), and were not cytotoxic in a Vero cell line. Tested for activity against M. tuberculosis DNA gyrase in a DNA supercoiling activity assay, 21a and 30a showed IC50 values (27-28 microM) comparable to that of ciprofloxacin (10.6 microM). 21a was next selected for screening against several Mtb strains obtained from clinical isolates, including multi-drug-resistant (MDR) variants. Importantly, this compound was effective in all cases, with very promising MIC values (4 microM) in the case of some isoniazid/rifampicin-resistant Mtb strains. Finally, computer-based simulations revealed that the binding mode of 21a in the Mtb gyrase cleavage core complexed with DNA and the relevant network of intermolecular interactions are utterly similar to those described for ciprofloxacin, yielding a molecular rationale for the comparable anti-mycobacterial and DNA gyrase inhibition activity of this quinolone

Additional polymorphisms of the <i>PRNP</i> gene significantly decrease the susceptibility to scrapie of ARQ/ARQ sheep

The aim of this work was to investigate the risk of scrapie of the ARQ/ARQ genotype carrying at least one point mutation at codons 112, 137, 141, 142, 154 and 176 in comparison with the ARQ/ARQ without any point mutations