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This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients' quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa β. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation.

ABSTRACT Transition is the next major hurdle in the field of HIV-infected youth, especially in sub-Saharan Africa. At St Camille Hospital in Ouagadougou, fully informed and compliant patients over 13-years-old were eligible for referral to the adult HIV/AIDS service, after completion of an individualized preparatory process. Transition consisted in at least two consecutive "joined-service" appointments in the respective facilities. We retrospectively compared immunological, clinical, and therapeutical data one year before transition, at transition and one year after transition. Between 2008 and 2019 73 patients (34 females, 39 males) were transitioned. All had been previously in pediatric care for at least 1 year and 66 were on HAART. Matched paired analysis of CD4 counts revealed a modest drop in CD4 cells over time ( p  < 0.05). Clinical data also showed strong fluctuation between WHO clinical stages over the three time points, with a clear trend towards increased severity especially post transfer. This large retrospective 12-year single-center experience from a Sahel country showed a 95.8% retention rate at one year. It demonstrates how a comprehensive plan, carefully implemented, can provide excellent retention, even in a low-resource setting. However, mild immunological decline was associated with a worrisome clinical deterioration, underlining the importance of assessing the latter after transition.

Although the numbers of SARS-CoV-2 infections and related deaths are relatively low in sub-Saharan Africa, the pandemic might lead to a high indirect death toll there. We determined the impact of the COVID-19 pandemic on the management of malnourished children in urban and rural areas. We analyzed data from two Centers for Rehabilitation, Education & Nutrition (CRENs), one in the capital and one in a rural center, both run by the Camillian Fathers. We compared data from the year before the pandemic (2019) with the first 2 years during the pandemic (2020/2021). In the urban CREN, there was a sharp reduction in new patients enrolled, from 340 in the pre-pandemic year to 189 during the first pandemic year and 202 in the second year. The follow-up was significantly shorter during the first pandemic year, with a rebound in the second year (pre: 57 days versus 42 and 63 days for the first and second years, respectively). In the rural CREN, the situation was different: The numbers of patients did not show any significant variation between the pre-pandemic year (191) and the first and second pandemic years (223 and 179, respectively). Different perceptions of the pandemic in urban (high, more testing, more COVID) and rural (low, less information and testing) areas may partly explain this difference. The discrepancy between the decreasing numbers of malnourished children in specialized care during the pandemic-especially in the urban area-is contrary to the lockdown-induced increase in food insecurity and warrants attention to avoid an increase in the silent epidemic of malnourished children in Africa.

Neglected tropical diseases (NTDs) affect mainly poor and marginalized populations of tropical and subtropical areas in 150 countries. Many of the chemical processes involved in the synthesis of active pharmaceutical ingredients (APIs) are highly polluting and inefficient, both in terms of materials and energy-consuming. In this review, we present the green protocols developed in the last 10 years to access new small molecules with potential applications in the treatment of leishmania, tuberculosis, malaria, and Chagas disease. The use of alternative and efficient energy sources, like microwaves and ultrasound, as well as reactions using green solvents and solvent-free protocols, are discussed in this review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Paclitaxel-induced peripheral neuropathy (PIPN) is a very common and complex painful condition related to paclitaxel (PTX) exposure, severely impacting patients' quality of life, and contributing to the emergence of clinical signs of anxiety and cognitive loss. At present, no sufficient treatment options are available for PIPN and its exact pathophysiology remains unclear. Based on the therapeutic potential of the 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), we assessed its ability to reverse PIPN and its comorbities induced by PTX. The effect of 4-PSQ was evaluated on pathophysiological processes involved in PIPN, such as oxidative stress (oxidative damage and antioxidant enzymes), neuroinflammation (mRNA expression levels of nuclear factor-kappa B, interleukin-1beta, tumor necrosis factor-alpha, and inducible nitric oxide synthase), and calcium homeostasis (Ca 2+ ATPase activity) in the spinal cord, cerebral cortex, and hippocampus of mice. Male Swiss mice received PTX (2 mg/kg) or vehicle by intraperitoneal route (days 1, 2, and 3). Oral administration of 4-PSQ (1 mg/kg) or vehicle was performed on days 3 to 14. It was observed that 4-PSQ reduced the mechanical and thermal hypersensitivities induced by PTX. Likewise, 4-PSQ reduced both anxious behavior and cognitive impairment in mice with PIPN. We believe that effects of 4-PSQ may be associated, at least in part, with the modulation of oxidative stress, reduction of neuroinflammation, and normalizing Ca 2+ ATPase activity in the spinal cord, cerebral cortex, and hippocampus of mice with PIPN. Taken together, the 4-PSQ might be a good prototype for the development of a more effective drug for the treatment of PIPN and its comorbities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This manuscript intends to overview the most recent advances in the synthesis of carbo- and heterocycles through reactions of alkynes with organyl chalcogenides (S, Se, Te) under metal-free conditions. Firstly, the use of electrophilic chalcogenyl halides as a selective reagent for alkyne carbon-carbon triple bond activation will be presented. After that, radical cyclization protocols employing electrochemical oxidative conditions, light-induced photoredox catalysis, or mild oxidants with direct chalcogenyl group installation will be discussed accompanied by the proposed mechanisms., (© 2021 The Chemical Society of Japan & Wiley-VCH GmbH.)

The object of this study was to investigate the frequency of human adenovirus (HAdV) infections in hospitalized pediatric patients. Stool samples were collected during a 1-year period (February 2018 to January 2019). HAdV was detected by a broad-range PCR and genotyped by sequencing and phylogenetic analysis. Demographic characteristics and detailed clinical information were analyzed for each patient. HAdV was detected in 7.1% of stool samples (34/476). Among these patients, 23.5% were coinfected with other enteric viral or bacterial pathogens. The majority (85.2%) of HAdV positives were detected in children of <5 years of age. Two HAdV species (B and C) with three types were identified in this study population. HAdV species F was not detected. Genetic analysis shows that the isolates circulating in our region present high diversity and do not exhibit clonal expansion. The presence of nonenteric HAdV in subjects with gastrointestinal symptoms and in immunocompromised patients has already been reported by different studies and underlines the need to develop routine molecular assays that have wide reactivity for most types of adenovirus in order to obtain an optimal tool for their rapid and accurate diagnosis. IMPORTANCE Gastroenteritis is the second leading cause of death among infants and children worldwide. Our study shows that adenovirus types other than 40 and 41 might be related to acute gastroenteritis. Therefore, a novel approach using diagnostic methods able to detect all adenovirus types is desirable in order to overcome the limitations of the current techniques.

Suppressive effect of bis (3-amino-2-pyridine) diselenide (BAPD) on psychiatric disorders - atopic dermatitis (AD) comorbidity in mice was investigated. To sensitize the animals, 2,4-dinitrochlorobenzene (DNCB) was applied to their dorsal skin on days 1-3. Mice were challenged with DNCB on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. BAPD and Dexamethasone were administered to the animals, from days 14-29, and skin severity scores and behavioral tests were determined. Oxidative stress and inflammatory parameters were evaluated on the dorsal skin of mice. Na + , K + -ATPase activity and corticosterone levels were determined in hippocampus/cerebral cortex and plasma of mice, respectively. BAPD improved cutaneous damage, scratching behavior, inflammatory and oxidative stress markers. BAPD showed anxiolytic- and antidepressant-like effects and restored Na + , K + -ATPase activity and corticosterone levels. The present study was performed using female mice due the susceptibility for this disease. But, the evaluation of AD model in male mice would help to verify whether the male gender has the same predisposition to present this pathology. Our data demonstrated the suppressive effect of BAPD on psychiatric disorders - AD comorbidity by regulating inflammatory and oxidative status in mice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Africa is the World Health Organization-region least affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Here, we compare the situation in severely hit Italy with that in less hit Burkina Faso, focussing on the differences in epidemiological, geographical, demographical, cultural and medical conditions to highlight how a full-blown war on the pandemic can impact on other, equally important aspects of global child health., (© The Author(s) [2020]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Less than 25% of children who require hematopoietic stem cell transplantation (HSCT) for primary immunodeficiencies (PIDs) or genetic hematological diseases have an HLA-identical sibling. For them, a matched unrelated donor (MUD), although baring a greater risk of graft failure, delayed engraftment and immune reconstitution, and severe graft-versus-host disease (GvHD), represents a valid alternative. The stem cell source is also important, as unprocessed peripheral blood stem cells (PBSCs) contain 5 to 10 times more T cells than bone marrow (BM)-derived grafts, a major risk especially for small children with PID. A CD34+ positive selection can mitigate HLA compatibility issues, but the resulting CD3+ T cell depletion hampers engraftment and facilitates infections. To mitigate those problems, we decided to add back a certain number of T cells (30 × 10 6 cells/kg body weight [BW]) to the positive CD34+ selection derived from MUD BM or PBSCs and report the results in terms of time to engraftment and immune reconstitution, GvHD incidence, infections, and survival. Our aim was to show not only the feasibility and clinical efficacy of this addback but also that PBSC-derived CD34+ selected grafts with calibrated T cell addback would be equivalent to BM-derived grafts. We analyzed retrospectively our single-center cohort of 76 children (median age, 1.9 years) affected by PID (61) and hematological diseases (15) who received a total of 79 MUD HSCTs with CD34+ selection and addback of 30 × 10 6 CD3+ cells/kg BW between 2001 and 2019. We used descriptive and analytic statistics (chi-square, Student's t-test, Mann-Whitney U test, as appropriate) and constructed Kaplan-Meier curves using the log-rank test to compare patients grafted with BM or PBSC-derived inocula. The two groups showed no statistically significant differences in terms of age, sex, HLA-mismatch, or amount of CD3+ cells/kg BW added back to the CD34+ selection. However, the latter being higher in the PBSC group (P = .0001). Overall engraftment rate was 96% (73/76) and occurred faster in the PBSC group than in BM recipients: polymorphonuclear cells, 16 versus 21 days (P = .006); platelets, 15 versus 22 days (P = .001). GvHD incidence was low. No acute GvHD was diagnosed in 24 children, whereas grades I, II, III, and IV occurred in 19, 28, five, and three children, respectively (P not significant). Chronic GvHD was seen in only two children. The CD4+ count at six months after HSCT was higher in PBSC recipients as compared to those receiving BM (184 versus 88 CD4+ cells; P = .003). Overall survival for the whole cohort was 80% at 10 years, with no significant difference between the two stem cell sources (P not significant). Viral infections occurred among five of the PBSC grafted children and 14 in the BM group (P not significant), and no patient suffered from post-transplant lymphoproliferative disorder (PTLD). The results we present show that an addback of 30 × 10 6 donor CD3+ cells/kg recipient BW to a MUD BM or PBSC-derived CD34+ selection gives promising results in infants and young children undergoing HSCT for PID or hematological diseases. Furthermore, with this manipulation the inherent limits of PBSC-derived grafts can be overcome, allowing both swift engraftment and immune reconstitution without an increase in GvHD, infections, or PTLD., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

There is increasing evidence that black people and other minorities have a higher incidence of severe COVID-19 disease, but little is known about the situation of children, especially in Europe. In general children are less infected and if so, frequently show mild or asymptomatic disease, making conclusions difficult. We collected data on SARS-CoV-2 associated hospitalizations in a well-defined population of 550,180 children up to 15 years in five hub-centers during the "first wave" at the heart of the pandemic in Northern Italy. Among the 451,053 Italian citizens 80 were hospitalized as compared to 31 out of 99,127 foreign citizens, giving a significantly higher risk (odds ratio 1.76; 95% CI: 1.16-2.66) for the foreign children. The risk was highest for children of African ethnicity as compared to Italians with an odds ratio of 2.76 (95% CI: 1.56-4.87). None of the patients deceased. There was no significant difference in age (thou infants regardless of ethnicity had a 10-fold higher risk), sex, length of hospitalization or comorbidities, namely overweight. As bureaucratic, cultural and information barriers mostly affect preventive and adult services and considering that in contrast to other countries, in Italy pediatric care is guaranteed free of (out-of-pocket) charge to all people <16 years, and hospitals are densely spaced, access to health care seems to be a minor problem. Thus, other possible root causes are discussed. We believe that this is an unbiased starting point to understand and overcome the reasons for the higher risk those children experience., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baronio, Savaré, Ruggiero, Crotti, Mazza, Marseglia, Dodi, Cavalli and Schumacher.)

We described herein a selective method to prepare α-organylthio esters and α-organylthio ketones by the reaction of β-keto esters with sodium S -benzyl sulfurothioate or sodium S -alkyl sulfurothioate (Bunte salts) under basic conditions in toluene as the solvent at 100 °C. When 4 equivalents of a base were used, a series of differently substituted α-thio esters were obtained with up to 90% yield. On the other hand, employing 2 equivalents of a base, α-thio ketones were achieved after 18 h under air. Furthermore, after a shorter reaction time, the isolation of keto-enol tautomers was possible, revealing them as significant intermediates for the mechanism elucidation., (Copyright © 2021, Kazmierczak et al.)

An alternative method to prepare 2-organylchalcogenopheno[2,3-b]pyridines was developed by the insertion of chalcogen species (selenium, sulfur or tellurium), generated in situ, into 2-chloro-3-(organylethynyl)pyridines by using the NaBH 4 /PEG-400 reducing system, followed by an intramolecular cyclization. It was possible to obtain a series of compounds with up to 93 % yield in short reaction times. Among the synthesized products, 2-organyltelluropheno[2,3-b]pyridines have not been described in the literature so far. Moreover, the compounds 2-phenylthieno[2,3-b]pyridine (3 b) and 2-phenyltelluropheno[2,3-b]pyridine (3 c) exhibited significant antioxidant potential in different in vitro assays. Further studies demonstrated that compound 3 b exerted an antinociceptive effect in acute inflammatory and non-inflammatory pain models, thus indicating the involvement of the central and peripheral nervous systems on its pharmacological action. More specifically, our results suggest that the intrinsic antioxidant property of compound 3 b might contribute to attenuating the nociception and inflammatory process on local injury induced by complete Freund's adjuvant (CFA)., (© 2020 Wiley-VCH GmbH.)

A simple and practical protocol for the synthesis of 3-selanyl-benzo[ b ]furans mediated by the SelectFluor® reagent was developed. This novel methodology provided a greener alternative to generate 3-substituted-benzo[ b ]furans via a metal-free procedure under mild conditions. The intramolecular cyclization reaction was carried out employing an electrophilic selenium species generated in situ through the reaction between SelectFluor® and organic diselenides. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy, and its reactivity was explored., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ewing sarcoma (ES) is one of the most common pediatric solid tumors with aggressive behavior and unfavorable survival. In this study, we evaluated the diagnostic accuracy of baseline and restaging fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scans and their possible prognostic role in pediatric ES. We evaluated 17 patients who underwent a total of 27 18F-FDG-PET/CT scans (10 for staging and 17 for restaging). The PET images were analyzed visually and semiquantitatively by measuring SUVmean, SUVmax, SUVlbm, SUVbsa, MTV, and TLG. Moreover, PET/CT results were compared with other conventional imaging (CI) results. Among 10 baseline PET/CT scan results, 9 were positive and 1 not valuable by interference; baseline PET/CT and CI were concordant in 7 cases and discordant in 2, with pulmonary micrometastases not detected by PET/CT. Among 17 restaging PET/CT scan results, 9 were positive and 8 negative; CI and restaging PET/CT were concordant in 9 cases and discordant in 8. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of restaging 18F-FDG-PET/CT were 73%, 83%, 89%, 62.5%, and 76%, respectively. After a median follow-up of 20 months, relapse/progression occurred in 8 patients and death in 5. A positive 18F-FDG-PET/CT at restaging was significantly associated with shorter overall survival compared with unremarkable PET/CT at the same timepoint, but not with progression-free survival. Instead, metabolic PET/CT features were not correlated with outcome. 18F-FDG-PET/CT showed a good diagnostic performance in pediatric ES; except for pulmonary micrometastases, PET/CT was better than CI at restaging. Only restaging PET/CT result was significantly correlated with overall survival.

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Rheumatoid arthritis (RA) can cause significant forefoot disorders. If forefoot deformity and pain are severe, surgical treatment can be considered. The aim of this study was to analyze the long-term outcomes of surgical forefoot correction per Tillmann, which involves resection of the metatarsal heads through a transverse plantar approach for the lesser toes and a dorsomedial approach to the great toe., Methods: This retrospective study used patient-based questionnaires to analyze the revision rate, pain, use of orthoses, walking ability, forefoot function, and patient satisfaction of patients with RA who had undergone a complete forefoot correction of metatarsophalangeal (MTP) I to V. The study only included participants with RA before the era of biological agents and who were at least 20 years postoperatively. A total of 60 patients who had undergone 100 complete forefoot operations according to Tillmann 24.6 ± 3.5 years ago were included in this study., Results: The data collected showed that 35 reoperations were performed on 26 of the patients. Deformity relapses were often documented for the hallux valgus. More than 60% of the patients were able to wear conventional shoes. The distances the participants were able to walk were significantly increased by wearing shoes when compared with walking barefoot ( P < .01)., Conclusion: While forefoot function remained difficult to assess, the majority of patients were able to use conventional shoes. This long-term follow-up study of patient-reported questionnaires completed more than 20 years after the Tillmann procedure showed that more than 80% of the patients remained satisfied with the outcome., Level of Evidence: Level IV, retrospective cohort study.

Background and aims: Primary immunodeficiencies (PID) are characterized by recurrent infections and increased risk of malignancies because of the reduced immunological surveillance against cancer cells and oncogenic viruses. Methods: We report the incidence of tumors among 690 patients with PID, diagnosed from 1990 until 2017 in Brescia. Results: Out of 690 patients, 25 patients (3.6%) developed 33 tumors. Of the 25 affected patients, 8 patients suffered from common variable immunodeficiency (CVID), 5 from combined immunodeficiency (CID), 3 from Ataxia-telangectasia (AT), 2 from Hermanksy-Pudlak type 2 (HSP2), 2 from gammaglobulinemia X-linked (XLA), 2 from Wiskott-Aldrich syndrome (WAS), 2 from Hyper IgE syndrome (HIES), 1 from severe combined immunodeficiency (SCID). The age at diagnosis ranged from 1 to 52 years, with a median age of 19.6 years. The time between the diagnosis of PID and onset of tumor was short, often <1 year between diagnosis and the appearance of cancer in the case of CID. Moreover, in two cases of CID, the diagnosis of cancer was made before the diagnosis of PID, so cancer was the onset clinical manifestation. Hematological malignancies were prevalent (22/33, 66.7%) with a minority of solid tumors (11/33, 33.33%). In particular Non-Hodgkin lymphomas were the most frequent (16/33, 48.48%). In total 13 patients survived (52%) and tumor was the main cause of death (7 cases). Two patients underwent BMT once the disease was in remission. Conclusions: Therefore, the correct management of tumors that arise in patients with primitive immunodeficiency still represents a challenge in the pediatric field. For this reason now it is mandatory to collect in a unique international registry the cases of malignancies in PID that could lead to a better understanding of the etiopathogenesis and of the biological and clinical characteristics of these tumors, with the aim of defining adequate preventive measures and guaranteeing an early diagnosis which also creating a shared and specific therapeutic strategy, with the prospect of obtaining a better prognosis for these patients.

In the present study, the synthesis of new selenoethers from nucleophilic substitution reaction between organyl halides and nucleophilic species of selenium generated in situ was demonstrated. After, this method was applied for the synthesis of pyridylselenides glycerol derivatives 9b and 9c and the antinociceptive and anti-inflammatory effects, as well as, acute toxicity were evaluated. In the formalin test, the compound 9b caused a reduction in licking time in both phases. Compounds 9b and 9c increased the latency to response in the hot-plate test and reduced the licking time induced by glutamate. Our results revealed the involvement of the nitrergic and/or glutamatergic pathways in the antinociceptive action of the compounds. Additionally, 9b and 9c did not cause any toxicity signals and oxidative stress parameters were not modified by treatments. Here, it was developed an alternative and efficient method for the synthesis of selenoethers glycerol derivatives. Furthermore, we demonstrated that this class is indeed interesting for the research of new drugs. Graphical Abstract ᅟ.

A one-pot iodine-catalyzed multicomponent reaction has been developed for the selective preparation of 5-amino-4-(arylselanyl)-1 H -pyrazoles from a diverse array of benzoylacetonitriles, arylhydrazines and diaryl diselenides. The reactions were conducted in MeCN as solvent at reflux temperature under air. The methodology presents a large functional group tolerance to electron-deficient, electron-rich, and bulky substituents and gave the expected products in good to excellent yields. The synthesized 1,3-diphenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine was submitted to an oxidative dehydrogenative coupling to produce a diazo compound confirmed by X-ray analysis.

MYC -translocated T-lineage acute lymphoblastic leukemia (T-ALL) is a rare subgroup of T-ALL associated with CDKN2A/B deletions, PTEN inactivation, and absence of NOTCH1 or FBXW7 mutations. This subtype of T-ALL has been associated with induction failure and aggressive disease. Identification of drug targets and mechanistic insights for this disease are still limited. Here, we established a human NOTCH1-independent MYC -translocated T-ALL cell line that maintains the genetic and phenotypic characteristics of the parental leukemic clone at diagnosis. The University of Padua T-cell acute lymphoblastic leukemia 13 (UP-ALL13) cell line has all the main features of the above described MYC -translocated T-ALL. Interestingly, UP-ALL13 was found to harbor a heterozygous R882H DNMT3A mutation typically found in myeloid leukemia. Chromatin immunoprecipitation coupled with high-throughput sequencing for histone H3 lysine 27 (H3K27) acetylation revealed numerous putative super-enhancers near key transcription factors, including MYC, MYB, and LEF1. Marked cytotoxicity was found following bromodomain-containing protein 4 (BRD4) inhibition with AZD5153, suggesting a strict dependency of this particular subtype of T-ALL on the activity of super-enhancers. Altogether, this cell line may be a useful model system for dissecting the signaling pathways implicated in NOTCH1-independent T-ALL and for the screening of targeted anti-leukemia agents specific for this T-ALL subgroup.

This article provides a comprehensive overview of reported methods - particularly copper- and organocatalyzed reactions - for the regioselective syntheses of selenium-containing 1,2,3-triazoles systems. These chemical entities are prevalent cores in biologically active compounds and functional materials. In view of their unique properties, substantial efforts have been paid for the design and development of practical approaches for the synthesis of these scaffolds., (© 2018 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We describe here a simple method for the synthesis of 6-arylselanylpurines with antioxidant and anticholinesterase activities, and memory improvement effect. This class of compounds was synthesized in good yields by a reaction of 6-chloropurine with diaryl diselenides using NaBH 4 as reducing agent and PEG-400 as solvent. Furthermore, the synthesized compounds were evaluated for their in vitro antioxidant and acetylcholinesterase (AChE) inhibitor activities. The best AChE inhibitor was assessed on the in vivo memory improvement. Our results demonstrated that the 6-((4-chlorophenyl)selanyl)-9H-purine and 6-(p-tolylselanyl)-9H-purine presented in vitro antioxidant effect. In addition, 6-((4-fluorophenyl)selanyl)-9H-purine inhibited the AChE activity and improved memory, being a promising therapeutic agent for the treatment of Alzheimer's disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Magnitude understanding is critical for students to develop a deep understanding of fractions and more advanced mathematics curriculum. The research reports in this special issue underscore magnitude understanding for fractions and emphasize number lines as both an assessment and an instructional tool. In this commentary, we discuss how number lines broaden the concept of fractions for students who are tied to the more general part-whole representations of area models. We also discuss how number lines, compared to other representations, are a superior and more mathematically correct way to explain fraction concepts.

In this article, the authors summarize results from 5 randomized controlled trials assessing the effects of intervention to improve the fraction performance of fourth-grade students at risk for difficulty in learning about fractions. The authors begin by explaining the importance of competence with fractions and why an instructional focus on fractions magnitude understanding may improve learning. They then describe an intervention that relies strongly on this type of understanding about fractions instruction, and they provide an overview of the intervention's overall effects. This is followed by an overview of 5 intervention components for which the authors isolated effects. They conclude by discussing some of the lessons learned from this research program.