Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

Major depressive episode with insomnia and excessive daytime sleepiness: A more homogeneous and severe subtype of depression.

Previous studies have noted the crucial role of excessive daytime sleepiness (EDS) in the course of depressive illness, and more recently, a few studies documented its strong associations with an increased risk of suicide. While insomnia is associated with heightened emotional reactivity, suicidal behaviors, and increased relapses and recurrence. Our main hypothesis is that major depressive episodes (MDE) with insomnia and EDS are associated with more severe manifestations of depression. However, to date, no study has directly compared MDE with insomnia without EDS (Ins), and MDE with insomnia with EDS (InsEDS) using both subjective biomarkers (administration of self-assessment questionnaires for psychiatric evaluation and sleep complaints) and objective biomarkers (of sleep and circadian rhythms (using actigraphy). The InsEDS group, compared to the Ins group, exhibited significantly increased suicidal ideation, larger seasonal impacts on mood, alterations in sleep duration, weight, appetite, energy levels, and social activities throughout the year. Furthermore, they had significant delayed onset of daily activity measured with actigraphy. These findings provided new insights into the link between suicide, sleep, alertness, and biological clock. They also hold significant implications for identifying individuals with more severe depressive manifestations and for developing tailored and personalized therapeutic strategies.

Latin American anaphylaxis registry.

Background: Recent data about clinical features, triggers and management of anaphylaxis in Latin America is lacking. Objective: To provide updated and extended data on anaphylaxis in this region. Method: An online questionnaire was used, with 67 allergy units involved from 12 Latin-American countries and Spain. Among data recorded, demographic information, clinical features, severity, triggering agents, and treatment were received. Results: Eight hundred and seventeen anaphylactic reactions were recorded. No difference in severity, regardless of pre-existing allergy or asthma history was found. Drug induced anaphylaxis (DIA) was most frequent (40.6%), followed by food induced anaphylaxis (FIA) (32.9%) and venom induced anaphylaxis (VIA) (12%). FIA and VIA were more common in children-adolescents. Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics (BLA) were the most frequent drugs involved. Milk (61.1% of FIA) and egg (15.4% of FIA) in children, and shellfish (25.5% of FIA), fresh fruits (14.2% of FIA), and fish (11.3% of FIA) in adults were the most common FIA triggers. Fire ants were the most frequent insect triggers, and they induced more severe reactions than triggers of FIA and DIA (p < 0.0001). Epinephrine was used in 43.8% of anaphylaxis episodes. After Emergency Department treatment, epinephrine was prescribed to 13% of patients. Conclusions: Drugs (NSAIDs and BLA), foods (milk and egg in children and shellfish, fruits and fish in adults) and fire ants were the most common inducers of anaphylaxis. Epinephrine was used in less than half of the episodes emphasizing the urgent need to improve dissemination and implementation of anaphylaxis guidelines.

Biochemical and structural studies of two tetrameric nucleoside 2'-deoxyribosyltransferases from psychrophilic and mesophilic bacteria: Insights into cold-adaptation.

Nucleoside 2'-deoxyribosyltransferases (NDTs) catalyze the cleavage of glycosidic bonds of 2'-deoxynucleosides and the following transfer of the 2'-deoxyribose moiety to acceptor nucleobases. Here, we report the crystal structures and biochemical properties of the first tetrameric NDTs: the type I NDT from the mesophilic bacterium Enterococcus faecalis V583 (EfPDT) and the type II NDT from the bacterium Desulfotalea psychrophila (DpNDT), the first psychrophilic NDT. This novel structural and biochemical data permitted an exhaustive comparative analysis aimed to shed light into the basis of the high global stability of the psychrophilic DpNDT, which has a higher melting temperature than EfPDT (58.5 °C versus 54.4 °C) or other mesophilic NDTs. DpNDT possesses a combination of unusual structural motifs not present neither in EfPDT nor any other NDT that most probably contribute to its global stability, in particular, a large aliphatic isoleucine-leucine-valine (ILV) bundle accompanied by a vicinal disulfide bridge and also an intersubunit disulfide bridge, the first described for an NDT. The functional and structural features of DpNDT do not fit the standard features of psychrophilic enzymes, which lead us to consider the implication of (sub)cellular levels together with the protein level in the adaptation of enzymatic activity to low temperatures.

NTRK Fusions Identified in Pediatric Tumors: The Frequency, Fusion Partners, and Clinical Outcome.

PURPOSE: Neurotrophic tyrosine receptor kinase (NTRK) fusions have been described as oncogenic drivers in a variety of tumors. However, little is known about the overall frequency of NTRK fusion in unselected pediatric tumors. Here, we assessed the frequency, fusion partners, and clinical course in pediatric patients with NTRK fusion-positive tumors. PATIENTS AND METHODS: We studied 1,347 consecutive pediatric tumors from 1,217 patients who underwent tumor genomic profiling using custom-designed DNA and RNA next-generation sequencing panels. NTRK fusions identified were orthogonally confirmed. RESULTS AND DISCUSSION: NTRK fusions were identified in 29 tumors from 27 patients with a positive yield of 2.22% for all patients and 3.08% for solid tumors. Although NTRK2 fusions were found exclusively in CNS tumors and NTRK1 fusions were highly enriched in papillary thyroid carcinomas, NTRK3 fusions were identified in all tumor categories. The most canonical fusion was ETV6-NTRK3 observed in 10 patients with diverse types of tumors. Several novel NTRK fusions were observed in rare tumor types, including KCTD16-NTRK1 in ganglioglioma and IRF2BP2-NTRK3 in papillary thyroid carcinomas. The detection of an NTRK fusion confirmed the morphologic diagnosis including five cases where the final tumor diagnosis was largely based on the discovery of an NTRK fusion. In one patient, the diagnosis was changed because of the identification of an ETV6-NTRK3 fusion. One patient with infantile fibrosarcoma was treated with larotrectinib and achieved complete pathologic remission. CONCLUSION: NTRK fusions are more frequently seen in pediatric tumors than in adult tumors and involve a broader panel of fusion partners and a wider range of tumors than previously recognized. These results highlight the importance of screening for NTRK fusions as part of the tumor genomic profiling for patients with pediatric cancer.

HPLC-PDA method validated for the determination of hibalactone in Hydrocotyle umbellata subterraneous parts and its ultrasound-assisted extraction optimization

ABSTRACT In this work, we developed and validated a HPLC-PDA method for the quantification of hibalactone in Hydrocotyle umbellata L., Araliaceae, subterraneous parts extracts and optimized its ultrasound-assisted extraction. Chromatographic separations were carried out with an isocratic mobile phase of acetonitrile/methanol/water (10:65:25), a flow of 0.8 ml min−1, detection at 290 nm and C18 column (250 × 4.6 mm, 5 µm). The method validation parameters were determined according to Brazilian legislation. The optimization of the hibalactone ultrasound-assisted extraction was performed using Box-Behnken design and response surface methodology. The HPLC method for hibalactone quantification proved to be selective, linear, precise, accurate and robust, being useful for the analysis of hibalactone in H. umbellata subterraneous parts extracts. The optimal ultrasound-assisted extraction conditions were obtained with solid-to-liquid ratio of 1:5 g ml−1, ethanolic strength of 70% (v/v) and temperature of 65 °C. The results can provide support of the quality control and standardization of raw materials from H. umbellata.

Robotic simple prostatectomy plus panniculectomy and Giant umbilical hernia repair.

INTRODUCTION: Simple prostatectomy is the gold standard for prostates >80 grams, robotic system has proven to help into speed the recovery of the patient and in morbid obesity the advantages of the robotic system can help to perform a successful surgery. CASE: 80 years old male with morbid obesity (BMI 45) and several other comorbidities, with history of an umbilical hernia and obstructive lower urinary tract symptoms in acute urinary retention. PSA was 7 ng/dl, DRE demonstrates a >100gr prostate gland. A robotic simple prostatectomy, urethropexy, umbilical hernia repair and panniculectomy in Fleur-de-Lis was performed. RESULTS: Operative time (OT) and estimated blood loss (EBL) were 438 min and 160 ml respectively. A JP drain was placed in the pelvis and 2 additional were left in the abdominal cavity with several Penrose drains. No immediate or intraoperative complications were observed. The length of stay (LOS) was 6 days without complications. Pathology report showed prostate of 304gr and benign prostatic tissue. DISCUSSION: In patients with multiple comorbidities robot-assisted surgery provides advantages of shorter LOS, EBL, less transfusion and lower rate of complications. In patients with morbid obesity where the increased girth makes difficult the open approach, robotic surgery is an ideal way to provide definitive treatment; concomitant, Fleur-de-Lis panniculectomy can correct the abdominal contour in both vertical and horizontal orientation at the same time that provides a better plane for trocar insertion, an accurate location of the needle tip and a proper position of the remote center decreasing the possible complication of port placement.

A Rare BSEP Mutation Associated with a Mild Form of Progressive Familial Intrahepatic Cholestasis Type 2

ABSTRACT Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2) is a rare cholestatic disorder diagnosed in infancy or childhood that can lead to severe hepatic fibrosis and liver failure. Mutations in the ABCB11 gene result in a deficiency of the bile salt export protein (BSEP) and accumulation of bile inside the hepatocytes. Hepatocellular carcinoma is another condition associated with severe forms of deletion mutations in the ABCB11 gene. Treatment options including ursodeoxycholic acid biliary diversion have mixed outcomes and some patients require liver transplantation. Here, we describe two siblings with an extremely mild form of PFIC2 inherited from heterozygous parents. The elder sibling had acute liver failure at the age of six months and both siblings had pruritus, cholestasis, coagulopathy and fat-soluble-vitamin deficiencies in infancy but have been asymptomatic past infancy. Genetic testing of the siblings revealed that each were compound heterozygotes for two missense mutations of the ABCB11 gene: p.C68Y and p.R832H. Medical treatment typical for PFIC2 has not been necessary for either patient. This is the first report of these variants following a mild course in two affected patients.(AU)

A Rare BSEP Mutation Associated with a Mild Form of Progressive Familial Intrahepatic Cholestasis Type 2.

Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2) is a rare cholestatic disorder diagnosed in infancy or childhood that can lead to severe hepatic fibrosis and liver failure. Mutations in the ABCB11 gene result in a deficiency of the bile salt export protein (BSEP) and accumulation of bile inside the hepatocytes. Hepatocellular carcinoma is another condition associated with severe forms of deletion mutations in the ABCB11 gene. Treatment options including ursodeoxycholic acid biliary diversion have mixed outcomes and some patients require liver transplantation. Here, we describe two siblings with an extremely mild form of PFIC2 inherited from heterozygous parents. The elder sibling had acute liver failure at the age of six months and both siblings had pruritus, cholestasis, coagulopathy and fat-soluble-vitamin deficiencies in infancy but have been asymptomatic past infancy. Genetic testing of the siblings revealed that each were compound heterozygotes for two missense mutations of the ABCB11 gene: p.C68Y and p.R832H. Medical treatment typical for PFIC2 has not been necessary for either patient. This is the first report of these variants following a mild course in two affected patients.

Breastfeeding, Dental Biofilm Acidogenicity, and Early Childhood Caries.

AIM: This study evaluated the acidogenicity of human milk by the dental biofilms of children with and without early childhood caries (ECC). METHOD: Biofilms of 16 children (7 with ECC; 9 caries free) were exposed to human milk or 10% sucrose solution in the crossover design, and the biofilm pH was determined. RESULTS: Breastfeeding did not provoke a decrease in biofilm pH, irrespective of the children's caries status, whereas sucrose decreased the pH for both groups. In addition, higher x0394;pH5min (pH variation occurring at 5 min) was observed in the biofilms of ECC children (p < 0.05). The results suggest that breastfeeding may not contribute to ECC.

Chemical composition of essential oils of leaves, flowers and fruits of Hortia oreadica

Abstract Hortia oreadica Groppo, Kallunki & Pirani, Rutaceae, known as “para-tudo”, “quina”, and “quina-do-campo”, is used in traditional medicine locally to treat stomach pain and fevers. The aims of this study were: analyze the chemical composition of essential oils from leaves, flowers and fruits of H. oreadica and verify the seasonal variation of the chemical components of essential oils from leaves. The essential oils were obtained by hydrodistillation using a Clevenger type apparatus and analyzed by GC/MS. The major components found in the samples of the essential oils were the amorpha-4,7(11)-diene (29.27% – flowers, 20.26% – fruits, 27.66–37.89% – leaves), bicyclogermacrene (23.28% – flowers, 20.64% – fruits, 14.71% to 31.37% – leaves). This work represents the first study of the chemical composition of essential oils from leaves, flowers and fruits and seasonal variation in the essential oils from leaves of H. oreadica.

Resistance exercise inter-set cooling strategy: effect on performance and muscle damage.

PURPOSE: To compare the effect of inter-set cooling and no cooling during resistance exercise (RE) on the total repetitions and select muscle damage biomarker responses. METHODS: Sixteen healthy men volunteered to participate in this study and were randomly assigned to Cooling (n = 8) or Control (n = 8) groups. They performed a RE protocol consisting of four sets of biceps curl at 80% of 1RM. The cooling group received the application of wet bags of ice during each interest rest interval (Cooling), while the Control realized the same protocol without ice application. Exercise was performed to voluntary fatigue and the numbers of repetitions per set were recorded. Subjects provided blood samples before and at 24, 48, and 72 h following RE to evaluate serum CK activity and myoglobin concentration. RESULTS: The Cooling group produced a greater number of repetitions (approx. 21%) than did the Control, but there were no differences in serum CK activity and myoglobin responses between the groups. CONCLUSION: Incorporating inter-set external cooling augments the number of repetitions per set during RE without inducing an additional muscle damage biomarker response.

Isolation and characterization of a heparin with low antithrombin activity from the body of Styela plicata (Chordata-Tunicata). Distinct effects on venous and arterial models of thrombosis.

INTRODUCTION: A heparin preparation with low antithrombin activity and different disaccharide composition than mammalian heparin was isolated from the body of the ascidian Styela plicata (Chordata-Tunicata). The disaccharide composition and the effect of the invertebrate glycan on venous and arterial models of thrombosis was investigated. METHODS AND RESULTS: High performance liquid chromatography of the products formed by a mixture of heparin lyases showed that the ascidian heparin is composed mainly by delta UA(2SO4)-1-->4-beta-d-GlcN(SO4) (47.5%), delta UA(2SO4)-1-->4-beta-d-GlcN(SO4)(6SO4) (38.3%) disaccharides and smaller amounts of the disaccharides delta UA(2SO4)-1-->4-beta-d-GlcN(SO4)(3SO4)(6SO4) (2.8%) and delta UA(2SO4)-1-->4-beta-d-GlcN(SO4)(3SO4) (8.0%). The invertebrate heparin has an aPTT activity of 18 IU/mg and an antithrombin-mediated antithrombin and anti-factor Xa activities 10-fold lower than that of mammalian heparin. In a venous model of thrombosis in the vena cava, S. plicata heparin inhibits only 80% of thrombosis at a dose 10-fold higher than that of the mammalian heparin that inhibits 100% of thrombosis. However, in an arterio-shunt model of arterial thrombosis, both S. plicata and mammalian heparin possess equivalent antithrombotic activities. It is also shown that at equivalent doses, ascidian heparin has a lower bleeding effect than mammalian heparin. CONCLUSION: The antithrombin-mediated anticoagulant activity of heparin polymers is not directly related to antithrombotic potency in the arterio-venous shunt. The results of the present work suggest that heparin preparations obtained from the body of S. plicata may have a safer therapeutic action in the treatment of arterial thrombosis than mammalian heparin.

The Hemolymph of the ascidian Styela plicata (Chordata-Tunicata) contains heparin inside basophil-like cells and a unique sulfated galactoglucan in the plasma.

The hemolymph of ascidians (Chordata-Tunicata) contains different types of hemocytes embedded in a liquid plasma. In the present study, heparin and a sulfated heteropolysaccharide were purified from the hemolymph of the ascidian Styela plicata. The heteropolysaccharide occurs free in the plasma, is composed of glucose ( approximately 60%) and galactose ( approximately 40%), and is highly sulfated. Heparin, on the other hand, occurs in the hemocytes, and high performance liquid chromatography of the products formed by degradation with specific lyases revealed that it is composed mainly by the disaccharides DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4)) (39.7%) and DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(6SO(4)) (38.2%). Small amounts of the 3-O-sulfated disaccharides DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(3SO(4)) (9.8%) and DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(3SO(4))(6SO(4)) (3.8%) were also detected. These 3-O-sulfated disaccharides were demonstrated to be essential for the binding of the hemocyte heparin to antithrombin III. Electron microscopy techniques were used to characterize the ultrastructure of the hemocytes and to localize heparin and histamine in these cells. At least five cell types were recognized and classified as univacuolated and multivacuolated cells, amebocytes, hemoblasts, and granulocytes. Immunocytochemistry showed that heparin and histamine co-localize in intracellular granules of only one type of hemocyte, the granulocyte. These results show for the first time that in ascidians, a sulfated galactoglucan circulates free in the plasma, and heparin occurs as an intracellular product of a circulating basophil-like cell.

Variabilidade sazonal do teor de saponinas de Baccharis trimera (Less. ) DC (Carqueja) e isolamento de flavona / Seasonal variability in the content of saponins from Baccharis trimera (Less. ) DC (Carqueja) and isolation of flavone

O objetivo deste trabalho foi avaliar a sazonalidade sobre o teor de saponinas e o isolamento e elucidação estrutural de constituinte químico (flavona) de Baccharis trimera (Less.) DC (Carqueja). O cultivo de indivíduos estaminados de B. trimera foi realizado no Campo Experimental da Universidade de Ribeirão Preto - Unaerp, em Ribeirão Preto, no período de janeiro a dezembro de 1998 e foi conduzido em três blocos, sendo que cada um deles era constituído de 48 mudas. As amostras foram colhidas após seis meses do plantio (durante o inverno), três meses após a primeira colheita (durante a primavera) e três meses após a segunda colheita (durante o verão). Após processo de secagem e moagem, as drogas foram submetidas ao ensaio para obtenção do índice de espuma. Os resultados mostraram que não há variabilidade neste índice em função da época de colheita. Parte da droga colhida no verão sofreu análise química para isolamento e elucidação estrutural de componente químico. O isolamento a partir do extrato metanólico de partes aéreas de B. trimera foi realizado através de métodos cromatográficos (CC e CLAE) e a identificação estrutural da substância isolada, através de métodos espectrométricos (UV, RMN ¹H e 13C). Foi identificada a flavona denominada 5,6-diidroxi-7,3,4-trimetoxiflavona.

The aim of this study was to evaluate the seasonal effect on the foam index and the isolation and structural identification of a chemical constituent (flavone) of Baccharis trimera. The culture staminate samples of B. trimera were realized in the experimental cultivation area of the Universidade de Ribeirão Preto - Unaerp, in Ribeirão Preto, state of São Paulo, Brazil from January to December/1998 and were conduced in three blocks, which received 48 seedlings. The samples were harvested six months after installation (during the winter), three months after the first harvest (during the spring) and three months after the second harvest (during the summer). After the drying process and comminution, an assay to obtain the foam index was performed with the plant material. The results didn't show any alteration, independently of harvest times. Part of the dried plant that had been harvested during the summer was extracted to isolate and identify structurally the chemical compound. The isolation from the methanol extracts of the aerial parts of B. trimera has been performed through chromatographic methods (CC and HPLC) and the identification through spectrometric methods (UV, ¹H and 13C NMR). A flavone was identified as 5,6-dihidroxy-7,3,4-trimetoxiflavone.

Differences in secondary metabolites from leaf extracts of Mikania glomerata Sprengel obtained by micropropagation and cuttings / Diferenças nos metabólitos secundários acumulados nos extratos das folhas de Mikania glomerata Sprengel obtidos por micropropagação e estaquia

GC analysis of the dichloromethane extracts obtained from cultivated specimens of Mikania glomerata Sprengel possibilited to verify that cuttings technique led to production of kaurenoic acid and coumarin while the same results have not been observed by propagation process using in vitro techniques.

A análise realizada por CG dos extratos diclorometânicos das folhas de Mikania glomerata Sprengel mostrou que a planta propagada por estaca produziu cumarina e ácido caurenóico, enquanto que o material micropropagado acumulou apenas cumarina.

Oxidative metabolism of 5-o-caffeoylquinic acid (chlorogenic acid), a bioactive natural product, by metalloporphyrin and rat liver mitochondria.

Synthetic metalloporphyrins, in the presence of monooxygen donors, are known to mimic the various reactions of cytochrome P450 enzymes systems in the oxidation and oxygenation of various drugs and biologically active compounds. This paper reports an HPLC-MS-MS investigation of chlorogenic acid (CGA) oxidation by iodosylbenzene using iron(III) tetraphenylporphyrin chloride as catalyst. The oxidation products have been detected by sequential MS analyses. In addition, CGA was submitted to an in vitro metabolism assay employing isolated rat liver mitochondria. The single oxidized product obtained from mitochondrial metabolism corresponds to the major product formed by the metalloporphyrin-catalyzed reaction. These results indicate that biomimetic oxidation reactions, in addition to in vitro metabolism assays employing isolated organs/organelles, could replace some in vivo metabolism studies, thus minimizing the problems related to the use of a large number of living animals in experimental research.

Esteróides e cumarina em calos de Mikania glomerata Sprengel / Steroides and coumarin from callus of Mikania Glomerata Sprengel

O estudo fitoquímico do extrato diclorometânico dos calos obtidos a partir de segmentos foliares de Mikania glomerata Sprengel resultou no isolamento dos esteróides campesterol, estigmasterol e ß-sitosterol e da cumarina, não tendo sido detectado nenhum diterpeno do tipo caurano