A Rare Cause of Vitamin B12 Deficiency in the Pediatric Age.

Vitamin B12 plays an important role in DNA synthesis, hematopoiesis, and neuronal mechanisms, and its deficiency can be associated with insufficient intake or poor absorption and autoimmune and genetic diseases. Although rare, excessive, and chronic alcohol consumption may also justify a deficiency in this vitamin. We present a case of a 17-year-old Iraqi adolescent refugee in Portugal with a deficiency of vitamin B12 due to excessive and chronic alcohol consumption. Although intramuscular (IM) supplementation with cyanocobalamin is the most used, it was decided to initiate oral supplementation. After four months, vitamin B12 levels were replenished. With this clinical case, we aim to raise awareness of the cause of cyanocobalamin deficiency, which although rare in pediatric age should be considered in adolescents, given the possibility of risky behaviors in this age group. Additionally, given the therapeutic options, we have found that oral administration of vitamin B12 has been effective, as reported in the literature.

Business cycle clocks: Time to get circular.

Assessing the momentum of the business cycle is of utmost importance for policymakers and private agents. In this respect, the use of business cycle clocks has gained prominence among national and international institutions to depict the current stage of the business cycle. Drawing on circular statistics, we propose a novel approach to business cycle clocks in a data-rich environment. The method is applied to the main euro area countries resorting to a large data set covering the last three decades. We document the usefulness of the circular business cycle clock to capture the business cycle stage, including peaks and troughs, with the findings being supported by the cross-country evidence.

The Daily Economic Indicator: tracking economic activity daily during the lockdown.

The SARS-CoV-2 outbreak made clear the urgent need to depart from traditional statistics, typically released with a lag and available at a relatively low frequency. This led to unparalleled efforts to put forward high-frequency indicators to track economic developments timely. By resorting to non-traditional data sources, we propose a novel daily economic indicator to track economic activity in Portugal. It corresponds to the latent variable of a set of daily series within a factor model framework. We find a sudden and sharp drop in economic activity in mid-March 2020, when the lockdown of several activities was declared due to the COVID-19 pandemic. Since in this approach we address the complexities of high-frequency data without further smoothing, we are able to identify sudden changes of economic activity in a timely and daily manner in contrast with other approaches.

Early Cardiac Mitochondrial Molecular and Functional Responses to Acute Anthracycline Treatment in Wistar Rats.

Doxorubicin (DOX) is an anticancer drug widely used to treat human and nonhuman tumors but the late and persistent cardio-toxicity reduces the therapeutic utility of the drug. The full mechanism(s) of DOX-induced acute, subchronic and delayed toxicity, which has a preponderant mitochondrial component, remains unclear; therefore, it is clinically relevant to identify early markers to identify patients who are predisposed to DOX-related cardiovascular toxicity. To address this, Wistar rats (16 weeks old) were treated with a single DOX dose (20 mg/kg, i.p.); then, mRNA, protein levels and functional analysis of mitochondrial endpoints were assessed 24 h later in the heart, liver, and kidney. Using an exploratory data analysis, we observed cardiac-specific alterations after DOX treatment for mitochondrial complexes III, IV, and preferentially for complex I. Conversely, the same analysis revealed complex II alterations are associated with DOX response in the liver and kidney. Interestingly, H2O2 production by the mitochondrial respiratory chain as well as loss of calcium-loading capacity, markers of subchronic toxicity, were not reliable indicators of acute DOX cardiotoxicity in this animal model. By using sequential principal component analysis and feature correlation analysis, we demonstrated for the first time alterations in sets of transcripts and proteins, but not functional measurements, that might serve as potential early acute markers of cardiac-specific mitochondrial toxicity, contributing to explain the trajectory of DOX cardiac toxicity and to develop novel interventions to minimize DOX cardiac liabilities.

A More Sustainable Process for Preparation of the Muscarinic Acetylcholine Antagonist Umeclidinium Bromide.

A more sustainable process for the synthesis of the long-acting muscarinic acetylcholine antagonist umeclidinium bromide is described. Specifically, we report the synthesis of ethyl 1-(2-chloroethyl)-4-piperidinecarboxylate, a key intermediate in the preparation of umeclidinium bromide, in good yields using triethylamine, as well as the identification and characterization of the by-product formed in this reaction. This new method of synthesis leads to an improvement in yield over that of previously reported protocols using potassium carbonate as base (65.6 % versus 38.6 %). Moreover, in the final synthetic step of the process to obtain umeclidinium bromide, we were able to replace the use of toxic solvents (acetonitrile/chloroform) with water. The use of this green solvent allowed precipitation of the active pharmaceutical ingredient (API) from the reaction medium with high purity and in high yield. Overall, we have developed a more efficient and environmentally friendly process for the synthesis of the umeclidinium bromide API with a higher overall yield (37.8 % versus previously reported overall yield of 9.7 %).

Intrusion Detection and Prevention in CoAP Wireless Sensor Networks Using Anomaly Detection.

It is well recognized that security will play a major role in enabling most of the applications envisioned for the Internet of Things (IoT). We must also note that most of such applications will employ sensing and actuating devices integrated with the Internet communications infrastructure and, from the minute such devices start to support end-to-end communications with external (Internet) hosts, they will be exposed to all kinds of threats and attacks. With this in mind, we propose an IDS framework for the detection and prevention of attacks in the context of Internet-integrated CoAP communication environments and, in the context of this framework, we implement and experimentally evaluate the effectiveness of anomaly-based intrusion detection, with the goal of detecting Denial of Service (DoS) attacks and attacks against the 6LoWPAN and CoAP communication protocols. From the results obtained in our experimental evaluation we observe that the proposed approach may viably protect devices against the considered attacks. We are able to achieve an accuracy of 93% considering the multi-class problem, thus when the pattern of specific intrusions is known. Considering the binary class problem, which allows us to recognize compromised devices, and though a lower accuracy of 92% is observed, a recall and an F_Measure of 98% were achieved. As far as our knowledge goes, ours is the first proposal targeting the usage of anomaly detection and prevention approaches to deal with application-layer and DoS attacks in 6LoWPAN and CoAP communication environments.

Morbidade neonatal dos recém-nascidos pré-termo tardios comparados aos de termo precoce / Neonatal morbidity of late preterm compared with early term neonates

OBJETIVOS: Avaliar e comparar a morbidade neonatal entre recém-nascidos pré-termo tardios (RNPT-T) e recém-nascidos de termo precoce (RNT-P). MÉTODOS: Estudo transversal retrospetivo, incluindo nascidos vivos em uma maternidade hospitalar de referência regional em Portugal, nos anos de 2014 e 2015, com idade gestacional entre 340/7 e 386/7 semanas. Os RNPT-T (340/7-366/7semanas) foram considerados casos e os RNT-P (370/7-386/7 semanas) foram considerados controles. Foram excluídos recém-nascidos com malformações congênitas, ausência de acompanhamento pré-natal e internação por motivo social ou causa materna. Foi avaliada e comparada a morbidade neonatal entre os dois grupos, utilizando o teste t de Student para comparação entre médias (variáveis contínuas) e o Qui-quadrado ou teste de Fisher para comparação entre variáveis categóricas. As odds ratio (OR) com seus respetivos intervalos de confiança (IC) 95% foram ajustadas (ORa) ao peso de nascimento, tipo de parto, patologia materna e gemelaridade. Considerou-se o valor p<0.05 como estatisticamente significativo. RESULTADOS: Foram avaliados 1.745 recém-nascidos, sendo 324 casos (RNPT-T) e 1.421 controles (RNT-P). Os RNPT-T associaram-se a maior frequência de hipertensão materna e diabetes gestacional e maiores taxas de gemelaridade e de cesariana. Os RNPT-T tiveram também um maior risco de necessidade de reanimação (OR=2,0 IC95% 1,3-3,0); hipoglicemia (ORa=4,9 IC95% 2,9-8,2); hiperbilirrubinemia (ORa=4,8 IC95% 3,7-6,2), taquipneia transitória (ORa=6,4 IC95% 4,0-10,3); dificuldades alimentares (ORa=6,6 IC95% 4,8-8,9); sepsis (ORa=4,4 IC95% 4,8-8,9); permanência hospitalar ≥5 dias (ORa=8,6 IC95% 6,6-11,3); e menor taxa de aleitamento materno exclusivo (ORa=0,2 IC95% 0,15-0,3). CONCLUSÕES: Em comparação aos RNT-P, os RNPT-T apresentaram maior risco de morbidade. Este estudo reforça a necessidade de um seguimento clínico apropriado aos RNPT-T no período neonatal.

AIMS: To evaluate and compare neonatal morbidity between late-preterm infants (LPTI) and early term infants (ETI). METHODS: Retrospective cross-sectional study, including live births at a regional referral maternity hospital in Portugal, in the years 2014 and 2015, with gestational age between 340/7 and 386/7 weeks. LPTI (340/7-366/7 weeks) were considered as cases and ETI (370/7-386/7 weeks) were considered controls. Neonates with congenital malformations, lack of prenatal care and hospitalization for social/maternal reasons were excluded. We evaluated and compared neonatal morbidity between the two groups, using Student's t-test for comparison between means (continuous variables) and Chi-square or Fisher's test for comparison between categorical variables. Odds ratio (OR) was calculated and adjusted (aOR) to birth weight, maternal disease, type of birth and multiple pregnancy. A value of p <0,05 was considered of statistical significance. RESULTS: A total of 1,745 neonates were evaluated: 324 cases (LPTI) and 1,421 controls (ETI). LPTI was associated with a higher frequency of maternal hypertension and gestational diabetes and higher rates of twinning and cesarean section. LPTI also had a higher risk for resuscitation (OR = 2.0 - 95%CI 1.3-3.0); hypoglycemia (aOR = 4.9 - 95%CI 2.9-8.2); hyperbilirubinemia (aOR = 4.8 - 95%CI 3.7-6.2), transient tachypnea (aOR = 6.4 - 95%CI 4.0-10.3); eating difficulties (aOR = 6.6 - 95%CI 4.8-8.9); sepsis (aOR = 4.4 - 95%CI 4.8-8.9); hospital stay ≥5 days (aOR = 8.6 - 95%CI 6.6-11.3); and lower exclusive breastfeeding rate (aOR = 0.2 - 95%CI 0.15-0.3). CONCLUSIONS: In comparison to ETI, LPTI presented a higher risk of morbidity. This study reinforces the need for appropriate clinical followup of LPTI in the neonatal period.

Enzymatic Kinetic Resolution of Secondary Alcohols Using an Ionic Anhydride Generated In†Situ.

We developed a method for the resolution of secondary alcohols using an ionic anhydride acylating agent prepared directly in the reaction medium containing the biocatalyst Candida antarctica lipase B (CALB). NMR studies showed that mixing all components at the same time does not interfere with the coupling reaction or the enzymatic activity. After optimization of the reaction conditions, the method allowed the resolution of a number of substrates in very high conversions (46-48 %) and enantiomeric ratios (E>170) along with an easy recovery of both enantiomers without the need for preparative chromatographic separation. Additionally, both the starting ionic acid and the biocatalyst could be recovered and reused up to nine cycles without significant loss of enantioselectivity.

Diet, Lifestyles, Family History, and Prostate Cancer Incidence in an East Algerian Patient Group.

Prostate cancer (PC) is the fourth most common cancer in men and the sixth leading cause of death in Algeria. To examine the relationship between lifestyle factors, including diet, and family history and PC risk, a case-control study was performed in an eastern Algerian population, comprising 90 patients with histologically confirmed PC and 190 controls. Data collection was carried out through a structured questionnaire and statistical analysis was performed to evaluate the different variables. The data showed that consumption of lamb and beef meat and high intake of animal fat and dairy products increased PC risk. Seven to thirteen vegetables servings per week and fourteen or more servings decreased PC risk by 62% and 96%, respectively. Seven to fourteen fruit servings per week decrease PC risk by 98%. Green tea consumption reduced the risk of PC but the results were statistically borderline. Increased risk was observed for individuals with family history of PC in first and in second degree. A positive strong association was also found for alcohol and smoking intake and a dose-response relationship existed for quantity and history of smoking. This study suggests that dietary habits, lifestyle factors, and family history have influence on the development of PC in Algerian population.

Ion jelly conductive properties using dicyanamide-based ionic liquids.

The thermal behavior and transport properties of several ion jellys (IJs), a composite that results from the combination of gelatin with an ionic liquid (IL), were investigated by dielectric relaxation spectroscopy (DRS), differential scanning calorimetry (DSC), and pulsed field gradient nuclear magnetic resonance spectroscopy (PFG NMR). Four different ILs containing the dicyanamide anion were used: 1-butyl-3-methylimidazolium dicyanamide (BMIMDCA), 1-ethyl-3-methylimidazolium dicyanamide (EMIMDCA), 1-butyl-1-methylpyrrolidinium dicyanamide (BMPyrDCA), and 1-butylpyridinium dicyanamide (BPyDCA); the bulk ILs were also investigated for comparison. A glass transition was detected by DSC for all materials, ILs and IJs, allowing them to be classified as glass formers. Additionally, an increase in the glass transition temperature upon dehydration was observed with a greater extent for IJs, attributed to a greater hindrance imposed by the gelatin matrix after water removal, rendering the IL less mobile. While crystallization is observed for some ILs with negligible water content, it was never detected for any IJ upon thermal cycling, which persist always as fully amorphous materials. From DRS measurements, conductivity and diffusion coefficients for both cations (D+) and anions (D-) were extracted. D+ values obtained by DRS reveal excellent agreement with those obtained from PFG NMR direct measurements, obeying the same VFTH equation over a large temperature range (ΔT ≈ 150 K) within which D+ varies around 10 decades. At temperatures close to room temperature, the IJs exhibit D values comparable to the most hydrated (9%) ILs. The IJ derived from EMIMDCA possesses the highest conductivity and diffusion coefficient, respectively, ∼10(-2) S·cm(-1) and ∼10(-10) m(2)·s(-1). For BMPyrDCA the relaxational behavior was analyzed through the complex permittivity and modulus formalism allowing the assignment of the detected secondary relaxation to a Johari-Goldstein process. Besides the relevant information on the more fundamental nature providing physicochemical details on ILs behavior, new doorways are opened for practical applications by using IJ as a strategy to produce novel and stable electrolytes for different electrochemical devices.

Ion jelly: a tailor-made conducting material for smart electrochemical devices.

We present a new concept for the design of a polymeric conducting material that combines the chemical versatility of an organic salt (ionic liquid) with the morphological versatility of a biopolymer (gelatin); the resulting 'ion jelly' can be applied in electrochemical devices, such as batteries, fuel cells, electrochromic windows or photovoltaic cells.

Efficient catalyst reuse by simple dissolution in non-conventional media.

This feature article is a description of the achievements made on the development of attractive sustainable approaches to synthetic organic chemistry, namely, catalyst reuse by simple dissolution in water and ionic liquids and asymmetric transformations induced by readily available chiral ionic liquids.

Simple transformation of crystalline chiral natural anions to liquid medium and their use to induce chirality.

New chiral ionic liquids can be prepared simply by combining the tetra-n-hexyl-dimethylguanidinium cation with readily available chiral anions and used as an asymmetric inducing agent as demonstrated for catalytic Rh(II) carbenoid C-H insertion and Sharpless dihydroxylation.

Synthesis of 2,4,6-tri-substituted-1,3,5-triazines.

Several specific synthetic protocols were developed for the preparation from cyanuric chloride of a range of symmetric and non-symmetric di- and tri-substituted 1,3,5-triazines containing alkyl, aromatic, hindered, chiral and achiral hydroxyalkyl, ester and imidazole groups via sequential nucleophilic substitution of the C-Cl bond by C-O, C-N and C-S bonds.

Effect of immobilization support, water activity, and enzyme ionization state on cutinase activity and enantioselectivity in organic media.

We studied the reaction between vinyl butyrate and 2-phenyl-1-propanol in acetonitrile catalyzed by Fusarium solani pisi cutinase immobilized on zeolites NaA and NaY and on Accurel PA-6. The choice of 2-phenyl-1-propanol was based on modeling studies that suggested moderate cutinase enantioselectivity towards this substrate. With all the supports, initial rates of transesterification were higher at a water activity (a(w)) of 0.2 than at a(w) = 0.7, and the reverse was true for initial rates of hydrolysis. By providing acid-base control in the medium through the use of solid-state buffers that control the parameter pH-pNa, which we monitored using an organo-soluble chromoionophoric indicator, we were able, in some cases, to completely eliminate dissolved butyric acid. However, none of the buffers used were able to improve the rates of transesterification relative to the blanks (no added buffer) when the enzyme was immobilized at an optimum pH of 8.5. When the enzyme was immobilized at pH 5 and exhibited only marginal activity, however, even a relatively acidic buffer with a pK(a) of 4.3 was able to restore catalytic activity to about 20% of that displayed for a pH of immobilization of 8.5, at otherwise identical conditions. As a(w) was increased from 0.2 to 0.7, rates of transesterification first increased slightly and then decreased. Rates of hydrolysis showed a steady increase in that a(w) range, and so did total initial reaction rates. The presence or absence of the buffers did not impact on the competition between transesterification and hydrolysis, regardless of whether the butyric acid formed remained as such in the reaction medium or was eliminated from the microenvironment of the enzyme through conversion into an insoluble salt. Cutinase enantioselectivity towards 2-phenyl-1-propanol was indeed low and was not affected by differences in immobilization support, enzyme protonation state, or a(w).