Role of Pegylated Interferon in Patients with Chronic Liver Diseases in the Context of SARS-CoV-2 Infection.

The coronavirus 2019 (COVID-19) pandemic has resulted in 168 million cases and about 3.5 million deaths (as of May 26, 2021) during the last 18 months. These 18 months of the COVID-19 pandemic have been characterized by phases or waves of new cases, the emergence of new variants of the deadly virus, and several new complications. After providing emergency approval to several drugs and adherence to several public health measures with frequent full and partial lockdowns, the incidence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could not be contained till now on a global basis. Although prophylactic vaccines have inspired optimism, the scarcity of vaccines and several vaccine-related regulations indicate that the vaccine's benefit would not be reaching the people of developing countries anytime soon. In the course of our clinical practice, we used pegylated interferon (Peg-IFN) in 35 patients with chronic liver diseases (CLD), and we found that only two of them were infected with SARS-CoV-2 that was mild in nature. These two patients with CLD have a mild course of disease cured without any specific therapy. Patients with CLD are usually immune-compromised. However, three CLD patients remained free of SARS-CoV-2 although they had COVID-19 patients among their family members. Next, we accomplished two studies for assessing the immune-modulatory capacities of Peg-IFN, 1 and 12 injections following administration of Peg-IFN. The data revealed that peripheral blood mononuclear cells (PBMCs) of Peg-IFN-administered CLD patients produced significantly higher levels of some cytokines of innate immunity in comparison with the cytokines produced by PBMC of CLD patients before Peg-IFN intake. The pattern of cytokine responses and absence of infection of SARS-CoV-2 in 33 of 35 CLD patients represent some preliminary observations indicating a possible role of Peg-IFN in patients with CLD. The study may be extended to other chronic infections and cancers in which patients receive Peg-IFN. The role of Peg-IFN for pre- or postexposure prophylaxis in the acquisition of SARS-CoV-2 infection and influencing the natural course of COVID-19 remains to be clarified. HOW TO CITE THIS ARTICLE: Akbar SMF, Mahtab MA, Aguilar JC, et al. Role of Pegylated Interferon in Patients with Chronic Liver Diseases in the Context of SARS-CoV-2 Infection. Euroasian J Hepato-Gastroenterol 2021;11(1):27-31.

Transrectal high-intensity focused ultrasound (HIFU) for management of rectosigmoid deep infiltrating endometriosis: results of Phase-I clinical trial.

OBJECTIVES: Deep infiltrating endometriosis (DIE) of the rectosigmoid is associated with painful symptoms. When medical treatment is ineffective, surgical resection remains the standard treatment, despite significant risk of adverse events. High-intensity focused ultrasound (HIFU) is a minimally invasive ablative procedure. Focal One® is a transrectal HIFU (TR-HIFU) device used in prostate cancer treatment. The primary objective of this study was to confirm the feasibility of treatment with TR-HIFU in patients presenting with posterior DIE with rectosigmoid involvement. We also assessed its safety and clinical efficacy in this context. METHODS: This was a non-controlled, prospective, Phase-I clinical trial in a French University Hospital which is a multidisciplinary center for management of endometriosis. Included were patients older than 25 years, without plans to conceive within 6 months, who presented with a single lesion of posterior DIE, with rectosigmoid invasion, after failure of hormonal therapy. All lesions were assessed preoperatively using transvaginal sonography and magnetic resonance imaging. Patients completed questionnaires on gynecological and intestinal symptoms (similar to a visual analog scale (VAS)), and on quality of life (Medical Outcomes Study 36-item short-form survey (SF-36) and, for the second half of patients recruited, symptom scoring system for constipation (KESS), female sexual function index (FSFI) and endometriosis health profile short-version score (EHP-5)), before, and at 1, 3 and 6 months after, TR-HIFU treatment with a Focal One real-time ultrasound-guided HIFU device. RESULTS: Twenty-three consecutive patients were included in the study between September 2015 and October 2019. All 23 lesions were visualized, giving a detection rate of 100%. Twenty lesions were treated ('feasibility rate', 87.0%): in 13 the whole lesion was treated and in seven the lesion was treated partially. The mean duration of the TR-HIFU procedure was 55.6 min. We observed a significant improvement in VAS score at 6 months, with differences relative to preoperative scores as follows, for: dysmenorrhea (-3.6, P = 0.004), dyspareunia (-2.4, P = 0.006), diarrhea (-3.0, P = 0.006), constipation (-3.0, P = 0.002), dyschezia (-3.2, P = 0.003), false urge to defecate (-3.3, P = 0.007), posterior pelvic pain (-3.8, P = 0.002) and asthenia (-3.8, P = 0.002). There was also a significant improvement in the SF-36 score, with an increase at 6 months relative to the preoperative score in both the physical component summary (+ 9.3%, P = 0.002) and mental component summary (+ 10.9%, P = 0.017). No major complications occurred during or after any procedure. CONCLUSIONS: TR-HIFU therapy for posterior DIE is feasible. If its efficacy and safety are confirmed, it could be a minimally invasive alternative to surgery for the treatment of rectosigmoid endometriosis. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Exposure to dogs but not cats is associated to a decrease in the prevalence in atopic dermatitis amongst school-children.

INTRODUCTION: The association regarding the exposure to pets, especially cats and dogs, and the prevalence of allergic diseases is inconsistent. OBJECTIVE: We analyzed the role played by early exposure to dogs or cats in the prevalence of allergic diseases amongst school-aged children. METHOD: Through a cross-sectional study, we examined 756 children, aged 6-7; these candidates were selected through cluster sampling. We inquired about the exposure that these children had had to dogs and cats, and whether these pets spent most of their time indoors or outdoors during the first year of the child's life. In order to identify the prevalence of allergic diseases and their symptoms, each child's parent completed the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: Exposure to outdoor dogs was associated to nocturnal coughing, odds ratio (OR) 0.64, with a confidence interval of 95% (95% CI) 0.43-0.95 and with atopic dermatitis (OR: 0.39; 95% CI: 0.20-0.76). Interestingly, exposure to outdoor cats was associated to nocturnal coughing (OR: 0.51; 95% CI: 0.32-0.83) and current rhinitis symptoms (OR: 0.59; 95% CI 0.36-0.97). After carrying out the multivariate analyses, only exposure to dogs, both indoor and outdoor, was significantly associated to a decrease in the prevalence of atopic dermatitis OR 0.40 (95% CI: 0.20-0.79) and OR 0.38 (95% CI: 0.18-0.83), respectively. CONCLUSION: Our findings suggest that exposure to dogs, whether they be indoor or outdoor pets, is associated to a decreased prevalence in atopic dermatitis.

[Systemic capillary leak syndrome: hypoalbuminemia, hemoconcentration and shock. Presentation of a case]. / Síndrome de fuga capilar sistémica: hipoalbuminemia, hemoconcentración y shock. A propósito de un caso.

Systemic capillary leak syndrome is a rare disorder of unknown etiology and often recurrent episodes characterized by increased capillary permeability that allows a leakage of fluid and proteins from the circulatory system to the interstitial space leading to shock and massive edema. The lack of recognition of this disease may be due to its unespecific signs and symptons of presentation, its rapid clinical progression and high mortality of the acute episodes. General physicians are usually the first to evaluate patients with this kind of disorder, either in the pre-hospital situation, hospital emergency units or even (in the milder cases) in the health centers. Its poor outcome and the improvement in the prognosis, if appropriate treatment is initiated, leads us to emphasize the importance of recognizing this pathology in order to start the appropriate intensive care and emergency treatment.

From vasospasm to early brain injury: new frontiers in subarachnoid haemorrhage research.

INTRODUCTION: Delayed vasospasm has traditionally been considered the most important determinant of poor outcome after subarachnoid haemorrhage (SAH). Consequently, most of the research and therapies are directed towards reducing the incidence of vasospasm (VSP). To date, however, clinical trials based on this strategy have not delivered a definitive treatment for preventing or reducing brain injury after SAH. This fact has caused a paradigm shift in research, which now focuses on early brain injury (EBI) occurring in the first 72 hours after SAH. It has also changed the idea of VSP's role in brain damage, and suggests the need for re-evaluating the pathophysiological process of SAH. DEVELOPMENT: This review examines the current state of knowledge on the pathophysiological mechanisms associated with EBI and summarises the diagnostic options currently available. CONCLUSION: It seems that the research approach needs to be changed so that investigators will focus on prevention of EBI, reduction of secondary brain complications and ultimately, the optimisation neurological outcome.

A functional study of nucleocytoplasmic transport signals of the EhNCABP166 protein from Entamoeba histolytica.

EhNCABP166 is an Entamoeba histolytica actin-binding protein that localizes to the nucleus and cytoplasm. Bioinformatic analysis of the EhNCABP166 amino acid sequence shows the presence of 3 bipartite nuclear localization signals (NLS) and a nuclear export signal (NES). The present study aimed to investigate the functionality of these signals in 3 ways. First, we fused each potential NLS to a cytoplasmic domain of ehFLN to determine whether the localization of this domain could be altered by the presence of the NLSs. Furthermore, the localization of each domain of EhNCABP166 was determined. Similarly, we generated mutations in the first block of bipartite signals from the domains that contained these signals. Additionally, we added an NES to 2 constructs that were then evaluated. We confirmed the intranuclear localization of EhNCABP166 using transmission electron microscopy. Fusion of each NLS resulted in shuttling of the cytoplasmic domain to the nucleus. With the exception of 2 domains, all of the evaluated domains localized within the nucleus. A mutation in the first block of bipartite signals affected the localization of the domains containing an NLS. The addition of an NES shifted the localization of these domains to the cytoplasm. The results presented here establish EhNCABP166 as a protein containing functional nuclear localization signals and a nuclear export signal.

New insights into host-pathogen interactions during Entamoeba histolytica liver infection.

Amoebiasis is the third worldwide disease due to a parasite. The causative agent of this disease, the unicellular eukaryote Entamoeba histolytica, causes dysentery and liver abscesses associated with inflammation and human cell death. During liver invasion, before entering the parenchyma, E. histolytica trophozoites are in contact with liver sinusoidal endothelial cells (LSEC). We present data characterizing human LSEC responses to interaction with E. histolytica and identifying amoebic factors involved in the process of cell death in this cell culture model potentially relevant for early steps of hepatic amoebiasis. E. histolytica interferes with host cell adhesion signalling and leads to diminished adhesion and target cell death. Contact with parasites induces disruption of actin stress fibers and focal adhesion complexes. We conclude that interference with LSEC signalling may result from amoeba-triggered changes in the mechanical forces in the vicinity of cells in contact with parasites, sensed and transmitted by focal adhesion complexes. The study highlights for the first time the potential role in the onset of hepatic amoebiasis of the loss of liver endothelium integrity by disturbance of focal adhesion function and adhesion signalling. Among the amoebic factors required for changed LSEC adherence properties we identified the Gal/GalNAC lectin, cysteine proteases and KERP1.

[Arreflexic coma and MELAS syndrome]. / Coma arrefléxico en el síndrome de MELAS.

MELAS is a progressive neurodegenerative and fatal disease characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. It is the result of a mitochondrial DNA mutation. Although the incidence of MELAS is currently unknown, it is suspected that approximately 1 out of every 5,000 persons world-wide have some type of defect in mitochondrial DNA. Cardinal clinical features observed in more than 90% of the patients include severe headache that may be associated with stroke-like episodes, seizures and the onset of symptoms before the age of 40 years. Diagnosis is established through genetic test or by with muscle biopsies that reveal the presence of ragged-red fibers. Prognosis is poor, with death at an early age. In this article, we present the clinical case of a 31-year old women diagnosed of MELAS syndrome who was admitted to the Intensive Care Unit of our hospital with arreflexic coma.

Structure and content of the Entamoeba histolytica genome.

The intestinal parasite Entamoeba histolytica is one of the first protists for which a draft genome sequence has been published. Although the genome is still incomplete, it is unlikely that many genes are missing from the list of those already identified. In this chapter we summarise the features of the genome as they are currently understood and provide previously unpublished analyses of many of the genes.

Signaling through the phosphatidylinositol 3-kinase regulates mechanotaxis induced by local low magnetic forces in Entamoeba histolytica.

In micro-organisms, as well as in metazoan cells, cellular polarization and directed migration are finely regulated by external stimuli, including mechanical stresses. The mechanisms sustaining the transduction of such external stresses into intracellular biochemical signals remain mainly unknown. Using an external magnetic tip, we generated a magnetic field gradient that allows migration analysis of cells submitted to local low-intensity magnetic forces (50 pN). We applied our system to the amoeba Entamoeba histolytica. Indeed, motility and chemotaxis are key activities that allow this parasite to invade and destroy the human tissues during amoebiasis. The magnetic force was applied either inside the cytoplasm or externally at the rear pole of the amoeba. We observed that the application of an intracellular force did not affect cell polarization and migration, whereas the application of the force at the rear pole of the cell induced a persistent polarization and strongly directional motion, almost directly opposed to the magnetic force. This phenomenon was completely abolished when phosphatidylinositol 3-kinase activity was inhibited by wortmanin. This result demonstrated that the applied mechanical stimulus was transduced and amplified into an intracellular biochemical signal, a process that allows such low-intensity force to strongly modify the migration behavior of the cell.

[Assessment of the acceptance of set meals served at the "Sant Joan de Reus" University Hospital]. / Evaluación de la aceptación de los menús servidos en el Hospital Universitari de Sant Joan de Reus.

Despite the fact that, in most of the series published, cancer is the most frequent base pathology for the indication of home parenteral nutrition (HPN), the use of this technique in terminally-ill patients is still a controversial issue. Our goal has been to review the evolution of cancer patients with HPN treatment from "La Paz" Hospital with a view to studying the indication, evolution and complications. We review a total of 9 terminal oncological patients who had been treated with HPN between January 2000 and December 2002, with a mean age of 60.4 (44-81) years, the most common base cancer was gastric adenocarcinoma (44%). Intestinal obstruction in the context of peritoneal carcinomatosis was the reason for indicating HPN in 89% of cases and the median survival time was 71 (23-131) days. Catheter infection was the most frequent complication with 1.4 episodes/patient. The existence of a Home Support Team meant follow-up of patients was easier, with HPN being estimated as the treatment provided in 67% of cases. 56% of the patients were not sufficiently informed as to their underlying illness. Although HPN is one more therapeutic resource, which may or may not be used in some terminal oncological patients, we must refine the indication as much as possible to take into account a series of "systematic guarantees" including fulfilment of pertinent clinical criteria, informed consent and the adoption of a collective decision with the involvement of all the professionals monitoring the patient. We propose an action algorithm to help in improving the decision-taking process in these patients.

A karyological study of the spirurid nematode Mastophorus muris (Nematoda: Spirocercidae).

The karyotype of Mastophorus muris (Gmelin, 1790) comprises four pairs of small autosomal chromosomes and two larger sex X chromosomes in females or one X chromosome in males (2n = 8 + XX/XO). All pairs of chromosomes possess rather uniform morphology without distinct primary or secondary constrictions. No heterochromatin bands were found by C-banding analysis. The absolute chromosome length ranges from 4.02 to 2.24 microns. The mean total length of the haploid complement is 14.34 microns. The course of gametogenesis represents a typical pattern common in the order Spirurida. The recently available karyotypes of spirurid nematodes have been reviewed.

[Food intake, dietary habits and nutritional status of the population of Reus (X): Evolution of the diet and the contribution of macronutrients to energy intake (1983-1999) by age and sex]. / Consumo, hábitos alimentarios y estado nutricional de la población de Reus (X): Evolución de la ingestión alimentaria y de la contribución de los macronutrientes al aporte energético (1983-1999), según edad y sexo.

BACKGROUND: To study the evolution of the diet and the nutritional intake between 1983 and 1999, by age and sex. SUBJECTS AND METHODS: We performed a series of analysis of the food intake on a representative sample of the population of Reus (aged 10-69 years). Dietary intake was estimated using the 24-hours recall method. In 1999 the sample size was 839 individuals, 41% of them having taken part in the studies since 1983. Results are shown as mean (standard deviation). RESULTS: In 1999, the energy intake was 2524 (582) kcal in men aged 35-44 years (n = 57), and 1827 (490) kcal in women (n = 95) (p < 0.001 between sexes). The energy intake decreases with age (significant trend [p < 0.001] between 15-69 years) and it is higher in men than in women in all the age groups studied. When comparing similar age groups, we observe that this energy intake has not changed significantly since 1983. Between 1983 and 1999 the contribution of the macronutrients to the total energy intake has become more similar between ages and sexes. In 1999, in men aged 35-44 years a 15.6% of the energy came from proteins, 42% from fat and 42.5% from carbohydrates; in women of the same age: a 17.3% of the energy came from proteins, 42.4% from fat and 40.3% from carbohydrates). During this period we observed, however, remarkable changes in the diet which imply the increasing participation of the dairy products, vegetables and meat in the energy intake, or the significant decrease of the role of tubers, eggs and visible fat. CONCLUSIONS: Our population maintains an energy intake without significant changes, and it presents a trend towards a progressive uniformity of the nutritional balance between the different ages and sexes, although there are significant changes in some components of the diet.

Cell polarization and adhesion in a motile pathogenic protozoan: role and fate of the Entamoeba histolytica Gal/GalNAc lectin.

The human pathogenic protozoan Entamoeba histolytica is a motile cell polarized into a front pseudopod and a rear uroid. The amoebic Gal/GalNAc surface lectin is a major adhesion molecule composed of an immunodominant 170-kDa heavy subunit, mostly extracellular except for a short cytoplasmic tail, and of an extracellular light subunit. The binding of multivalent ligands triggers lectin capping and recruitment to the uroid. The properties of the Gal/GalNAc lectin and its role in amoeba adhesion and uroid polarization are reviewed in the context of the molecular mechanisms underlying cell polarization and locomotion.