Acute gastric volvulus secondary to H-type tracheo-oesophageal fistula.

H-type tracheo-oesophageal fistula is an uncommon type of tracheo-oesophageal malformation. Acute gastric volvulus is another infrequent pathology in children. They rarely present together.We report the case of a toddler with acute gastric volvulus possibly secondary to an undiagnosed H-type tracheo-oesophageal fistula. The fistula was suspected due to persistent gastric distention observed during volvulus detorsion. This kind of tracheo-oesophageal fistula often presents with subtle symptoms making early diagnosis difficult.Acute gastric volvulus is a life-threatening condition. Gastric distension caused by the passage of air into the stomach through the fistula could be a triggering factor for gastric volvulus.

Differentiation of Synanthropic Fleas from Andalusia (Spain) through Geometric Morphometrics Analysis.

Fleas (Siphonaptera) are ectoparasitic hematophagous insects responsible for causing bites and itchy skin conditions in both humans and animals. Furthermore, they can act as vectors of different pathogens of a wide variety of diseases worldwide, including bartonellosis, rickettsiosis, and bubonic plague. Accurate identification of fleas is necessary for the study of their epidemiology, prevention, and control. In addition to traditional morphological classification approaches and molecular biology techniques, geometric morphometrics is increasingly proving to be a useful complementary tool for discriminating between Siphonaptera taxa. With the objective of determining the capacity of this technique to identify and differentiate synanthropic fleas, a principal component analysis was carried out on populations of Ctenocephalides felis, Pulex irritans, and Archaeopsylla erinacei collected in distinct regions of Andalusia (Spain). The analysis carried out on 81 male and female specimens revealed factorial maps that allowed the differentiation of the populations under study, with only partial overlaps that did not prevent their correct identification. Global size differences were also detected, with a slightly larger size in P. irritans males and a bigger size in A. erinacei females. Therefore, the present study emphasizes the role of geometric morphometrics as a useful complementary technique in taxonomic studies of arthropods, especially in the case of flea specimens lacking representative morphological features.

Survey of flea infestation in cats and dogs in Western Andalusia, Spain: Seasonality and other risk factors for flea infestation.

This epidemiological survey aims to provide an update on the main flea species that parasitize domestic animals in the Western Andalusia assessing several ecological features that could be considered as possible risk factors for flea infestation. Over a 19-month period (June 2021 to January 2023), we obtained a total of 802 flea samples from 182 dogs (Canis lupus familiaris, Carnivora: Canidae, Linnaeus, 1758) and 78 cats (Felis silvestris catus, Carnivora: Felidae, Schreber, 1775). For each parasitized host, an epidemiological survey was completed, including the following information: geographical origin, age, sex, rural or urban habitat, type of animal's lifestyle (domestic or non-domestic), health status, cohabiting or not with other animals and the total number of collected fleas. The most common species was Ctenocephalides felis (Siphonaptera: Pulicidae) (Bouché, 1835) with a total of 713 specimens, which accounted for 89% of the total fleas. The second most abundant species was Pulex irritans (Siphonaptera: Pulicidae) (Linnaeus, 1758) with a total of 46 collected fleas (6% of the total). The remaining species identified were Archaeopsylla erinacei (Siphonaptera: Pulicidae) (Bouché, 1835) (25 specimens), Spilopsyllus cuniculi (Siphonaptera: Pulicidae) (Dale, 1878) (12 specimens) and Ctenocephalides canis (Siphonaptera: Pulicidae) (Curtis, 1826) (6 specimens), which accounted for 3%, 1% and 1%, respectively, of the total fleas collected. The months with the highest number of collected fleas were, in ascending order, May 2022, September 2021 and July 2021. Dogs had a greater diversity of flea species, and flea sex ratios were female biased in all identified species and among all studied hosts. Finally, we identified some potential host risk factors that promoted higher flea intensities, such as living in rural areas, or presenting other pathologies.

Assessment of the change of antiemetic prophylaxis from double to triple combination in patients with high dose carboplatin chemotherapy.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC) therapy versus ondansetron and dexamethasone double combination (DC) therapy as antiemetic prophylaxis in patients with carboplatin AUC ≥ 4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 h to 15 min before chemotherapy. METHODS: Open-label prospective study conducted in a tertiary-care hospital in patients receiving carboplatin AUC ≥ 4. CINV was evaluated using MASCC antiemetic tool, in acute (<24 h) and delayed phase (24-120 h). Results were analyzed using χ2 test. RESULTS: Two-hundred four completed questionnaires (CQ) were analyzed (76 in DC and 128 in TC). The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92.1%, p = 0.0115) and delayed phase (97.6% vs 90.7%, p = 0.043). Likewise, a higher proportion of TC-treated patients compared to DC remained nausea-free for the first 24 h after treatment (90.6% vs 71%, p = 0.0004) and between 24 and 120 h (82.3% vs 62.7%, p = 0.0025). The change of NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5%, p = 0.70). CONCLUSIONS: TC showed superiority in early and delayed CINV control in carboplatin AUC ≥ 4 regimens, with no significant differences among cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospitals before chemotherapy session.

Ectopic variceal bleeding secondary to porto-sinusoidal vascular disease.

Porto-sinusoidal vascular disease (PSVD) is an uncommon cause of portal hypertension (PHT) characterized by typical manifestations of PHT in the absence of an identifiable cause such as cirrhosis or splenoportal thrombosis (1). There are different etiological factors, including oxaliplatin (2). We present the case of a 67-year-old male with a history of locally advanced rectal cancer in 2007 treated with chemotherapy (capecitabine, folinic acid, 5-fluorouracil and oxaliplatin), radiotherapy and surgery with a definitive colostomy. He was admitted for lower gastrointestinal bleeding from the colostomy with no anemia or hemodynamic repercussion. Colonoscopy was performed and no lesions were found. Abdominal computed tomography (CT) showed peristomal varices with porto-systemic collaterals at that level. There was splenomegaly, no evidence of chronic liver disease and the splenoportal axis was permeable. Laboratory tests showed chronic thrombocytopenia. Laboratory results excluded other causes of liver disease, hepatic elastography showed a value of 7.2 kPa and upper gastrointestinal endoscopy ruled out esophagogastric varices. The catheterisation of hepatic veins demonstrated a hepatic venous pressure gradient of 13.5 mmHg and liver biopsy revealed sinusoidal dilatation with sinusoidal and perivenular fibrosis. Because of the clinical context of the patient with a history of treatment with oxaliplatin, he was diagnosed with peristomal ectopic varices secondary to porto-sinusoidal vascular disease. Due to bleeding recurrence, it was finally decided to place a transjugular intrahepatic portosystemic shunt (TIPS).

Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides.

Methionine sulfoxide reductase A (MsrA) enzymes have recently found applications as nonoxidative biocatalysts in the enantioselective kinetic resolution of racemic sulfoxides. This work describes the identification of selective and robust MsrA biocatalysts able to catalyze the enantioselective reduction of a variety of aromatic and aliphatic chiral sulfoxides at 8-64 mM concentration with high yields and excellent ees (up to 99%). Moreover, with the aim to expand the substrate scope of MsrA biocatalysts, a library of mutant enzymes has been designed via rational mutagenesis utilizing in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies. The mutant enzyme MsrA33 was found to catalyze the kinetic resolution of bulky sulfoxide substrates bearing non-methyl substituents on the sulfur atom with ees up to 99%, overcoming a significant limitation of the currently available MsrA biocatalysts.

Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein.

The use of computer-aided methods have continued to propel accelerated drug discovery across various disease models, interestingly allowing the specific inhibition of pathogenic targets. Chloride Intracellular Channel Protein 4 (CLIC4) is a novel class of intracellular ion channel highly implicated in tumor and vascular biology. It regulates cell proliferation, apoptosis and angiogenesis; and is involved in multiple pathologic signaling pathways. Absence of specific inhibitors however impedes its advancement to translational research. Here, we integrate structural bioinformatics and experimental research approaches for the discovery and validation of small-molecule inhibitors of CLIC4. High-affinity allosteric binders were identified from a library of 1615 Food and Drug Administration (FDA)-approved drugs via a high-performance computing-powered blind-docking approach, resulting in the selection of amphotericin B and rapamycin. NMR assays confirmed the binding and conformational disruptive effects of both drugs while they also reversed stress-induced membrane translocation of CLIC4 and inhibited endothelial cell migration. Structural and dynamics simulation studies further revealed that the inhibitory mechanisms of these compounds were hinged on the allosteric modulation of the catalytic glutathione (GSH)-like site loop and the extended catalytic ß loop which may elicit interference with the catalytic activities of CLIC4. Structure-based insights from this study provide the basis for the selective targeting of CLIC4 to treat the associated pathologies.

Impact of digital technologies upon teaching and learning in higher education in Latin America: an outlook on the reach, barriers, and bottlenecks.

Digital technology and literacy can heighten the transformation of teaching and learning in higher education institutions (HEIs). This study uncovers the extent to which digital technologies have been used to advance the teaching and learning process in HEIs, and the barriers and bottlenecks to why it may not have been effectively implemented across the HEIs. The study used nine selected countries in Latin America (LATAM) based on the main focus of the educators, commercial, and financial investors; to show the level of impact/implications of computer technologies on the teaching and learning processes. We applied a two-step (mixed) methodology (through a quantitative and qualitative lens) for the research investigation, using data collected from survey we administered to faculty members in HEIs across the different countries in LATAM. In turn, we implemented a Text Mining technique (sentiment and emotional valence analysis) to analyze opinions (textual data) given by the participants to help determine challenges and obstacles to using the digital technologies for teaching and learning in the region. Quantitatively, we applied a Kruskal-Wallis H-test to analyze the collected multiple choice and ranked items in the questionnaire in order to identify prominent factors that consummately influence the reach, barriers, and bottlenecks, and where the differences may lie across the different LATAM countries. The results show that the users upheld the emphasis on lack of training, infrastructures and resources, access to internet and digital platforms, as the main challenges to the teaching-learning process. The study also empirically discussed and shed light on critical factors the HEIs, particularly in LATAM, should resolve and adopt in support of the decision-making strategies, operational policies and governance, financial investments, and policymaking, at a time when "digital technologies" have become an inevitable and indispensable part of education and learning.

One more step in the study of children's daily stress: The spillover effect as the transfer of tension in family and school environments.

Introduction: The spillover effect is the psychological overflow due to daily stress in one context and the transfer of its consequences to another close environment. The aim is to explore the spillover effect in conflicts within the family, on the one hand, and school with peers on the other hand, as an inferred measure of daily stress according to the literature. Method: The study consisted of a sample of 208 6-year-old students and their families. A methodology based on daily report records was used, by means of two ad hoc checklists with simultaneous measurements, for 2 consecutive weeks and 3 academic years, for both family and school contexts. A repeated measures design, together with a nonparametric statistical data analysis with Friedman's test and contrast measures, was used. Results: Daily stress shows significant differences in the family setting throughout the week (χ 2 = 32.44; p = 0.000) and at different times of the day (χ 2 = 29.65; p = 0.000). In the school setting, differences were found across the different days of the week (χ 2 = 36.96; p = 0.000). Spillover effect has been discovered between conflicts at home in the evening and conflicts at school. At the same time, conflicts at school are related to conflicts at home from Wednesday onward. Discussion: The results suggest further research on daily stress through the interrelation of the different contexts, as well as the impact that moments of conflict may have on the psychological and emotional development of the child.

Real-world data with the use of caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura: A single-center with homogeneous treatment experience.

BACKGROUND: Recently, real-world data confirmed the effectiveness of caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP); however, limitations as different treatment protocols from multicenter experiences and the front-line use of rituximab could overshadow the real impact of the addition of caplacizumab. STUDY DESIGN AND METHODS: We report the clinical characteristics and response to treatment of 30 consecutive cases of aTTP treated under a homogeneous therapeutic protocol with the only exception of the addition of caplacizumab in the last 10 cases (caplacizumab group), whose primary outcome we compare with the previous 20 cases (control group). RESULTS: Caplacizumab was started at a median of 2.5 days after diagnosis (interquartile range [IQR] 1-4) and maintained for a median of 37.5 days (IQR 32-39). Safety was in line with previous reports with 30% of patients showing mild adverse events, the most common bleeding. The caplacizumab group achieved platelet count normalization after a median of 3 (IQR 2-5) versus 4 (IQR 2-8.5) days in the control group (p = .067). The caplacizumab group required a lower median number of plasma exchanges, 10 (IQR 9-11) versus 16.5 (IQR 11-20) in the control group (p = .0053) and a shorter length of hospitalization, 12 (IQR 12-14) vs. 22 (IQR 15-27) days (p = .0025). There were no refractory cases and no deaths in the caplacizumab group compared to five refractory cases and three aTTP-related death (15%) in the control group. DISCUSSION: Our experience confirms improvement in the outcomes with a decrease in refractoriness and mortality since the introduction of caplacizumab.

Protective measures against Omicron could be more effective than Evusheld® in liver transplant recipients.

Evusheld (the combination of cilgavimab and tixagevimab, two long-lasting monoclonal antibodies against SARS-CoV-2) has been approved by the FDA as a pre-exposure treatment for COVID-19 in immunocompromised patients older than 12 years. However, this monoclonal antibody has been developed from SARS-CoV-2 variants that were predominant at the beginning of the pandemic, when Ómicron was not prevalent. Compared with other solid organ transplant recipients, liver transplant recipients have shown an excellent immune response to standard vaccination with three doses of the SARS-CoV-2 vaccine. In addition, this population has shown very good adherence to protective measures for the transmission of COVID-19 infection. Several studies have shown that the use of Evusheld is less effective against Ómicron than against other variants of SARS-CoV-2. In addition, in the post-hoc analysis, it appears to be a drug that increases cardiovascular risk. For these reasons, we believe that in liver transplant recipients is essential to prioritize vaccination and protective measures, rather than the use of Evusheld as pre-exposure prophylaxis.

Morphometrics as a Complementary Tool in the Differentiation of Two Cosmopolitan Flea Species: Ctenocephalides felis and Ctenocephalides canis.

Fleas (Siphonaptera) are one of the most important ectoparasites that represent a potential danger for the transmission of pathogens in our environment. The cat flea, Ctenocephalides felis (Bouché, 1835), and the dog flea, Ctenocephalides canis (Curtis, 1826) are among the most prevalent and most frequently studied species throughout the world. However, the variations observed in their morphological characteristics complicate their correct identification, especially when there is a lack of access to the equipment and funds required to carry out molecular biology techniques. With the objective to provide an additional tool to help in the differentiation of Ctenocephalides species, a principal component analysis was carried out for the first time in the present work on populations of C. felis and C. canis from countries in three continents, namely Spain (Europe), South Africa (Africa) and Iran (Asia). The factor maps assisted in the differentiation of both species and the detection of differences in overall size, although morphological ambiguity prevented the delimitation in populations of the same species. Thus, morphometrics represents a complementary tool to other traditional and modern techniques, with great potential to assist in the differentiation of fleas, particularly species that have historically been difficult to identify.

Anemia megaloblástica. A propósito de un caso / Megaloblastic anemia

La OMS reporta anemia en 24,8% de la población con predominio en países en desarrollo. La anemia megaloblástica, es una causa frecuente en la población adulta mayor. Se caracteriza por alteración en la síntesis de ácido desoxirribonucleico por deficiencia de vitamina B12 y/o folatos. Presentamos el caso de una mujer con manifestaciones clínicas y alteraciones de laboratorio características. Recibió tratamiento combinado con cianocobalamina y ácido fólico. Paulatinamente presentó reversión clínica y laboratorial. A pesar del nombre, la anemia megaloblástica, suele cursar con anemia, bicitopenia o ancitopenia y alteraciones sistémicas. Es obligatorio buscar la causa desencadenante para instaurar el tratamiento completo.

The WHO reports anemia in 24.8% of the population mainly in developing countries. Megaloblastic anemia is a frequent cause in the elderly population and it is due to an impaired synthesis of deoxyribonucleic acid. A deficiency of vitamin B12 and / or folic acid are the main causes. We present the case of a woman with characteristic clinical manifestations and laboratory abnormalities. She was treated with cyanocobalamin and folic acid. She improved and her laboratory tests got to normal gradually. Despite the name, megaloblastic anemia usually presents anemia, bicytopenia or pancytopenia and systemic manifestations. It is mandatory to search for the etiologic cause to make a complete treatment.

Comparative molecular and morphological study of Stenoponia tripectinata tripectinata (Siphonaptera: Stenoponiidae) from the Canary Islands and Corsica.

Stenoponia tripectinata tripectinata (Tiraboschi, 1902) is the most prevalent subspecies, within the genus Stenoponia, in the Mediterranean area. This rodent flea is widely distributed throughout southwestern Europe and the North of Africa including Mediterranean islands and the Canary Islands. Nevertheless, from a taxonomical and systematic point, this flea group has been neglected over the years. Therefore, the aim of this study was to carry out a comparative morphometric, phylogenetic, and molecular study of two populations of S. t. tripectinata isolated from rodents collected from different islands from the Canary Archipelago and from Corsica to clarify the taxonomic status of these two isolated populations and to assess the morphological and molecular differentiation between them. For this purpose, we have analyzed several morphological traits and sequenced five molecular markers (EF1-α, ITS2, cox1, cox2, and cytb). We observed slight differences in the overall body size between females of both populations, and two well-defined geographical genetic lineages. This suggests the existence of two cryptic subspecies within S. t. tripectinata corresponding to two different island groups. Furthermore, we bring to light the necessity to provide new and updated morphological, molecular, and phylogenetic data to clarify the taxonomic status of S. tripectinata.

Hypothyroidism confers tolerance to cerebral malaria.

The modulation of the host's metabolism to protect tissue from damage induces tolerance to infections increasing survival. Here, we examined the role of the thyroid hormones, key metabolic regulators, in the outcome of malaria. Hypothyroidism confers protection to experimental cerebral malaria by a disease tolerance mechanism. Hypothyroid mice display increased survival after infection with Plasmodium berghei ANKA, diminishing intracranial pressure and brain damage, without altering pathogen burden, blood-brain barrier disruption, or immune cell infiltration. This protection is reversed by treatment with a Sirtuin 1 inhibitor, while treatment of euthyroid mice with a Sirtuin 1 activator induces tolerance and reduces intracranial pressure and lethality. This indicates that thyroid hormones and Sirtuin 1 are previously unknown targets for cerebral malaria treatment, a major killer of children in endemic malaria areas.

Characterization of trichuris species from porcupine (Hystrix cristata) at zoological garden of Spain.

Population of Trichuris sp. isolated from Hystrix cristata was analyzed based on morphological, biometrical characteristics and mitochondrial (cox1, cob, rrnL) and ribosomal (ITS1) (rDNA) region sequences. Morphological and biometrical results revealed that Trichuris sp. from H. cristata present a high similarity with Trichuris landak from Hystrix javanica and less similarity with other Trichuris species from porcupine species (Trichuris hystricis, Trichuris lenkorani and Trichuris mettami). The lack of molecular data corresponding to Trichuris species that parasitize the porcupine (genus Hystrix and Atelerix) has not allowed a comparative molecular or phylogenetic study. Molecular analyses revealed the existence of two different haplotypes that did not correspond to different morphospecies. Relationships among Trichuris sp. from H. cristata and other Trichuris spp. have been resolved by molecular sequence data in this study. Thus, the combined analysis of one ribosomal and three mitochondrial markers revealed a sister relationship between whipworms parasitizing porcupine and other Trichuris spp. from rodents and canids and separated from the rest of Trichuris spp. from other hosts species. It is necessary accurate information on the possible zoonotic behavior of different Trichuris species for health workers to improve existing control measures. Thus, it is necessary to increase the studies of integrative taxonomy on Trichuris spp. based on morphological, biometrical and molecular data, which will inevitably contribute to our knowledge on the etiology of trichuriasis.

Proteomic quantitative study of dorsal root ganglia and sciatic nerve in type 2 diabetic mice.

OBJECTIVE: Peripheral neuropathy is the most common and debilitating complication of type 2 diabetes, leading to sensory loss, dysautonomia, hyperalgesia, and spontaneous noxious sensations. Despite the clinical and economic burden of diabetic neuropathy, no effective treatment is available. More preclinical research must be conducted in order to gain further understanding of the aetiology of the disease and elucidate new therapeutic targets. METHODS: The proteome of lumbar dorsal root ganglia and sciatic nerve of BKS-db/db mice, which contain a mutation of the leptin receptor and are an established type 2 diabetes model, was characterized for the first time by tandem mass tag labelling and mass spectrometry analysis. RESULTS: Proteomic analysis showed differentially expressed proteins grouped into functional clusters in db/db peripheral nerves compared to control mice, underlining reduced glycolytic and TCA cycle metabolism, higher lipid catabolism, upregulation of muscle-like proteins in DRG and downregulation in SCN, increased cytoskeleton-related proteins, a mild dysregulation of folding chaperones, activation of acute-phase and inflammatory response, and alterations in glutathione metabolism and oxidative stress related proteins. CONCLUSIONS: Our data validate previous transcriptomic and metabolomic results and uncover new pathways altered in diabetic neuropathy. Our results point out that energetic deficiency could represent the main mechanism of neurodegeneration observed in diabetic neuropathy. These findings may provide important information to select appropriate targets to develop new therapeutic strategies.

Bacterial communities from Trichuris spp. A contribution to deciphering the role of parasitic nematodes as vector of pathogens.

Microbiome taxa associated with parasitic nematodes is unknown. These invertebrate parasites could act not only as reservoirs and vectors for horizontally transferred virulence factors, but could also provide a potential pool of future emerging pathogens. Trichuris trichiura and Trichuris suis are geohelminths parasitizing the caecum of primates, including humans, and pigs, respectively. The present work is a preliminary study to evaluate the bacterial communities associated with T. trichiura and T. suis, using High Throughput Sequencing and checking the possible presence of pathogens in these nematodes, to determine whether parasitic helminths act as vectors for bacterial pathogens in human and animal hosts. Five T. trichiura adult specimens were obtained from the caecum of macaque (Macaca sylvanus) and two T. suis adults were collected from the caecum of swine (Sus scrofa domestica). The 16S rRNA gene HTS approach was employed to investigate the composition and diversity of bacterial communities in Trichuris spp., with special emphasis at its intestinal level. All samples showed a rich colonization by bacteria, included, preferently, in the phyla Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Cyanobacteria and Verrucomicrobia. A total of 36 phyla and more than 200 families were identified in the samples. Potential pathogen bacteria were detected in these helminths related to the genera Bartonella, Mycobacterium, Rickettsia, Salmonella, Escherichia/Shigella, Aeromonas and Clostridium. The presence of pathogenic bacteria in Trichuris spp. would position these species as a new threat to humans since these nematodes could spread new diseases. This study will also contribute to the understanding of the host-microbiota relation.