• Agger Sandberg opublikował 5 miesięcy, 2 tygodnie temu

    The fatality rate was the most important factor for internal policies, while the degree of global spread was the most important for border control policies. In general, individuals who were less healthy, had higher-income, and were older were more likely to support these policies. Perceived effectiveness of a policy was a consistent and positive predictor of public support.

    Our findings suggest that campaigns to promote public support should be designed specifically to each policy and tailored to different segments of the population. They should also be adapted based on the evolving conditions of the outbreak in order to receive continued public support.

    Our findings suggest that campaigns to promote public support should be designed specifically to each policy and tailored to different segments of the population. They should also be adapted based on the evolving conditions of the outbreak in order to receive continued public support.Tinnitus is a common symptom of a phantom sound perception with a considerable socioeconomic impact. Tinnitus pathophysiology is enigmatic and its significant heterogeneity reflects a wide spectrum of clinical manifestations, severity and annoyance among tinnitus sufferers. Although several interventions have been suggested, currently there is no universally accepted treatment. Moreover, there is no well-established correlation between tinnitus features or patients’ characteristics and projection of treatment response. At the clinical level, this practically means that selection of treatment is not based on expected outcomes for the particular patient.The complexity of tinnitus and lack of well-adapted prognostic factors for treatment selection highlight a potential role for a decision support system (DSS). A DSS is an informative system, based on big data that aims to facilitate decision-making based on specific rules, retrospective data reflecting results, patient profiling and predictive models. Therefore, DSS will be based and the algorithms that will be used for prognosis and treatment selection.The coronavirus disease-2019 (COVID-19) has rapidly become a pandemic, resulting in a global suspension of non-emergency medical procedures such as screening endoscopic examinations. There have been several reports of COVID-19 patients presenting with gastrointestinal symptoms such as diarrhea and vomiting. In this report, we present a case of successful hemostasis of bleeding gastric inflammatory fibroid polyp by endoscopic treatment in a patient with severe COVID-19. The case was under mechanical ventilation with extracorporeal membrane oxygenation (ECMO), and the airway was on a closed circuit. This indicates that COVID-19 is associated with not only lung injury but also intestinal damage, and that proper protective protocols are essential in guaranteeing the best outcomes for patients and clinical professionals during this pandemic.

    To explore the possible moderating relation between impulsive behavior and maladaptive personality traits in regards to orthorexia nervosa (ON).

    This cross-sectional study was conducted between July and December 2019 and recruited 519 Lebanese adults from seven community pharmacies randomly selected from a list provided by the Lebanese Order of Pharmacists. The Teruel Orthorexia Scale (TOS) was employed to assess orthorexic eating tendencies, the I-8 measured impulsivity and the Personality Inventory for DSM-5 (PID) evaluated maladaptive personality traits.

    Our results showed that, for I-8 subscales, only higher perseverance (B = 0.31) was significantly associated with higher ON. In regard to PID-5 subscales, only higher negative affect (B = - 0.34) was significantly associated with lower ON. Furthermore, significant interactions were found between personality traits and impulsivity to predict TOS-ON.

    The current results show that female gender, maladaptive personality traits and impulsivity present contributing factors regarding orthorexic eating. Certain impulsivity dimensions were confirmed to interact with personality traits in the prediction of orthorexic eating thereby highlighting possible risk factors and psychopathological mechanisms.

    Level V, cross-sectional descriptive study.

    Level V, cross-sectional descriptive study.

    Management of a child’s anxiety early in their treatment is essential in dentistry. Sedative medications are used to overcome increased anxiety from previous appointments and to promote the cooperation of children during treatment. Hydroxyzine is currently prescribed to young patients as part of the first level of conscious sedation. The main objective was to evaluate the professional practice of oral hydroxyzine, when prescribed for children presenting anxiety during dental treatment procedure performed by students and senior practitioners.

    A retrospective study of dental records and questionnaires was conducted at the Dental Care Centre of the University Hospital of Rennes, France. Parameters related to the prescription of hydroxyzine in children were evaluated as potential predictors of the dental session success, with adjustments on potential confounders.

    The therapeutic outcome was very encouraging with 78.3% of success during dental sessions under sedation with oral hydroxyzine. Anxiety levels befof pediatric treatment. This solution should be the first step in sedation to help practicing clinicians.

    The term „metabolic flexibility” denotes the dynamic responses of the cellular oxidative machinery in order to adapt to changes in energy substrate availability. A progressive loss of this adaptive capacity has been implicated in the development of obesity-related comorbidities. Mitochondria are dynamic intracellular organelles which play a fundamental role in energy metabolism, and the mitochondrial adaptation to environmental challenges may be viewed as the functional component of metabolic flexibility. Herein, we attempt to comprehensively review the available evidence regarding the role of mitochondrial adaptation and metabolic flexibility in the pathogenesis of obesity and related morbidities, namely insulin resistance states and non-alcoholic fatty liver disease (NAFLD).

    Overall, there is a concrete body of evidence to support the presence of impaired mitochondrial adaptation as a principal component of systemic metabolic inflexibility in conditions related to obesity. There are still many unresolveions regarding the relationship between the gradual loss of mitochondrial adaptability and the progression of obesity-related complications, such as causality issues, the timely appearance and reversibility of the described disturbances, and the generalizability of the findings to the mitochondrial content of every affected tissue or organ. The evidence regarding the causality between the observed associations remains inconclusive, although most of the available data points towards a bidirectional, potentially mutually amplifying relationship. The spectrum of NAFLD is of particular interest, since functional and pathological changes in the course of its development closely mirror the progression of dysmetabolism, if not constituting a dynamic component of the latter.The demand for functional foods is increasing each year because consumers are gaining awareness about the importance of a healthy diet in the proper functioning of the body. Probiotics are among the most commonly known, commercialized, and studied foods. However, the loss of viability of probiotic products is observed during their formulation, processing, and storage. This study aimed to investigate the co-encapsulation of two Lactobacillus paracasei probiotic strains (LBC81 and ELBAL) with fructooligosaccharides (FOS) in a calcium alginate matrix using extrusion technology with gelatin as a coating material. The viability of the strains under gastrointestinal conditions and in storage at low temperature was also assessed. An immobilization yield of more than 59% was observed for both bacterial strains. Exposure to 2% biliary salts led to a decrease in the viability of free cells in the two L. paracasei strains, whereas the viability of microencapsulated cells increased up to 47%. After 35 days of storage at 4°C, the population of free cells was reduced, but microencapsulated cells remained stable after storage at low temperature. LBC81 bacteria microencapsulated with 1.5% FOS coated with gelatin were the most resistant to the stressful environments tested. Therefore, these results showed that co-encapsulation with FOS in a calcium alginate matrix coated with gelatin improved L. paracasei survival and may be useful for the development of more resistant probiotics and new functional foods.We developed a new technique to reduce the length of the enteric defect to be closed during intracorporeal anastomosis in laparoscopic right hemicolectomy (LRH), also avoiding the need to suture the first part of the anastomosis in a deep space with an acute angle. From January 2017, after the ileo-colic anastomosis was completed, an additional stapler cartridge was applied starting at the colonic rim and including the small bowel part of the anastomosis. The isoperistaltic fashion of the ileo-colonic anastomosis was maintained. The remaining defect left to be closed was 2-3 cm. We compared the results of the novel technique with those of the 'standard’ closure (full-length enterotomy). In the last 30 months, this technique was successfully used in 32 patients (Group A), compared with 33 patients (2012-2016) operated with 'standard’ closure (Group B). Age, BMI and post-operative stage distribution were similar. The mean operative time was 175.2 min (± 36.7) in Group A and 165.9 min (± 42.5) in Group B (p = ns), with 53.1% and 27.3% of associated procedures (cholecystectomy, ovariectomy, etc.), respectively (p  less then  0.05). Overall morbidity rate was 28.1% and 30.3% (Group A vs Group B, p = ns), with no anastomotic bleeding/leak in either group. This technique, which simplifies the closure of the enteric defect after LRH with intracorporeal anastomosis is safe, reproducible and easy to learn. It might help more surgeons to perform a fully laparoscopic procedure in right hemicolectomy, offering the advantages of intracorporeal anastomosis to their patients.

    The COVID-19 pandemic brought unprecedented conditions for overall health care systems by restricting resources for non-COVID-19 patients. As the burden of the disease escalates, routine elective surgeries are being cancelled. The aim of this paper was to provide a guideline for management of endocrine surgical disorders during a pandemic.

    We used Delphi method with a nine-scale Likert scale on two rounds of voting involving 64 experienced eminent surgeons and endocrinologists who had the necessary experience to provide insight on endocrine disorder management. All voting was done by email using a standard questionnaire.

    Overall, 37 recommendations were voted on. In two rounds, all recommendations reached an agreement and were either endorsed or rejected. Endorsed statements include dietary change in primary hyperparathyroidism, Cinacalcet treatment in secondary hyperparathyroidism, alpha-blocker administration for pheochromocytoma, methimazole ± β-blocker combination for Graves’ disease, and follow-up for fine-needle aspiration results of thyroid nodules indicated as Bethesda 3-4 cytological results and papillary microcarcinoma.

    This survey summarizes expert opinion for the management of endocrine surgical conditions during unprecedented times when access to surgical treatment is severely disrupted. The statements are not applicable in circumstances in which surgical treatment is possible.

    This survey summarizes expert opinion for the management of endocrine surgical conditions during unprecedented times when access to surgical treatment is severely disrupted. The statements are not applicable in circumstances in which surgical treatment is possible.

    In low- to middle-income countries such as Vietnam, urgent measures are required to prevent and control type2 diabetes and its complications. This study measured the effect of a 3-month patient education and self-management intervention in a low-resource setting on diabetes knowledge and levels of blood glucose control.

    This was a single-center randomized controlled study among adult outpatients with type2 diabetes. Patients were randomly assigned to 3-month community intervention consisting of group education for type2 diabetes knowledge, diet, exercise in combination with usual diabetes care, or to usual diabetes care alone (control). Diabetes knowledge was measured with a modified Michigan University Diabetes Knowledge Test (MDKT). Other study outcomes included change in mean HbA1c, fasting blood glucose (FBG), and systolic blood pressure (SBP).

    A total of 364 patients were randomized, 182 to the intervention group and 182 to control. The two groups were similar regarding main baseline characteristic in the intervention group at 3months, but not in the control group. Multivariate analysis revealed the variables with the strongest influence on blood glucose control at 3months were study group, baseline MDKT score, diabetes duration, and baseline HbA1c (all P ≤ 0.05).

    Provision of a structured educational program to Vietnamese people living with type2 diabetes is effective at improving disease knowledge and is associated with better glycemic control. Larger and longer-term studies are now warranted to confirm these findings.

    This trial was retrospectively registered on 27 May 2020 through the https//clinicaltrials.gov site with the following identifierNCT04403841.

    This trial was retrospectively registered on 27 May 2020 through the https//clinicaltrials.gov site with the following identifier NCT04403841.

    Trends on glycemic control and diabetes complications are known for high-income countries, but comprehensive data from low- and middle-income countries (LMIC) are lacking.

    This is an expert opinion based on two retrospective studies. Here we examine the recent subset analysis of relevant data from the IDMPS Wave 7 (International Diabetes Management-Practices Study, 2015-2016) and the GOAL study conducted in multiple LMICs.

    Wave 7 sub-analysis was performed in 6113 people with type 2 diabetes from 24 LMIC. Poorly controlled diabetes (hemogloblin A1c [HbA1c] ≥ 7%) was found in 58.6, 73.0 and 78.3% of participants with diabetes duration of < 5, 5-12 and > 12years, respectively (in association with a high prevalence of macro- and microvascular complications). Moreover, 37.7% of participants with diabetes duration of 5-12years were treated only with oral antihyperglycemic drugs. The GOAL study investigated the efficacy of insulin in 2704 poorly controlled participants (mean HbA1c 9.7%; diabetes duratioDANCE study), and the incidence of microvascular complications was higher. The GOAL study showed that insulin treatment improves glycemic control and reduces this gap. The Expert Panel recommends intensifying diabetes treatment as soon as possible, as well as patients’ education and other preventive measures, initiatives which require modest costs compared to hospitalization and treatment of diabetes complications.

    Exercise stress echocardiography has been used to assess myocardial reserve in various heart diseases. This study examined the ventricular myocardial response to exercise in Fontan patients using exercise stress echocardiography.

    Twenty-five Fontan patients and 19 control subjects underwent semi-supine bicycle exercise stress echocardiography in this prospective, single-center, cross-sectional study. Pulsed-wave Doppler tissue imaging peak systolic (s’) and diastolic (e’) velocities, longitudinal strain and systolic strain rate, and early diastolic strain rate data at rest and at peak exercise were obtained for the systemic ventricle. The myocardial reserve of functional parameters was calculated as the difference between peak exercise and rest.

    Inter- and intra-observer reliability were both high for exercise stress echocardiography measurements. Compared with controls, Fontan patients had significantly lower s’, e’, longitudinal systolic strain and strain rate, and early diastolic longitudinal strain rate at rest and at peak exercise as well as reduced myocardial reserve.

    Fontan patients have markedly reduced myocardial reserve during exercise. The use of exercise stress echocardiography assessment may improve the clinical management of Fontan patients.

    Fontan patients have markedly reduced myocardial reserve during exercise. The use of exercise stress echocardiography assessment may improve the clinical management of Fontan patients.

    Neovascular age-related macular degeneration (nAMD) presents a significant treatment burden for patients, carers and medical retina services. However, significant debate remains regarding how best to manage nAMD when assessing disease activity by optical coherence tomography (OCT), and particularly the significance of different types of fluid and how the understanding of anatomical efficacy can influence treatment strategies. This article provides opinion on the practical implications of anatomical efficacy and significance of fluid in the management of nAMD and proposes recommendations for healthcare professionals (HCPs) to improve understanding and promote best practice to achieve disease control.

    An evidence-based review was performed and an expert panel debate from the Retina Outcomes Group (ROG), a forum of retinal specialists, provided insights and recommendations on the definition, role and practical implications of anatomical efficacy and the significance of fluid at the macula in the management outlined recommendations aim to promote best practice among HCPs and medical retina services to improve patient outcomes.

    Mutations in mitochondrial DNA (mtDNA) are found to be associated with type 2 diabetes mellitus (T2DM). However, the molecular pathogenesis of these mutations in T2DM is still poorly understood.

    In this study, we report here the molecular features of two Han Chinese families with maternally transmitted T2DM. The matrilineal relatives are undergoing clinical, biochemical, genetic evaluations, and molecular analysis. Furthermore, the entire mitochondrial genomes of these matrilineal relatives are screened by PCR-Sanger sequencing.

    The age at onset of T2DM of these participants varies from 28 to 71years, with an average of 43years. Molecular analysis of mitochondrial genomes identifies the existence of ND1 T3394C mutation in both families, together with sets of variants belonging to mitochondrial haplogroup Y2 and M9a. The m.T3394C mutation is localized at very conserved tyrosine at position 30 of ND1, may result the failure in ND1 mRNA metabolism, and lead to mitochondrial dysfunction. Moreover, sequence analysis of matrilineal relatives in Family 1 identifies the m.A14693G mutation which occurs in the TΨC-loop of tRNA

    (position 54), and is critical to the structural formation and stabilization of this tRNA. Thus, m.A14693G mutation may cause the impairment in tRNA metabolism, thereby worsens the mitochondrial dysfunction caused by ND1 T3394C mutation. However, no functional mtDNA variants are identified in Family 2 which suggest that mitochondrial haplogroup may not play an important role in diabetes expression.

    Our study indicates that mitochondrial ND1 T3394C mutation is involved in the pathogenesis of maternally inherited T2DM in these families.

    Our study indicates that mitochondrial ND1 T3394C mutation is involved in the pathogenesis of maternally inherited T2DM in these families.

    Endogenous biomarkers are promising tools to assess transporter-mediated drug-drug interactions early in humans.

    We evaluated on a common and validated in vitro system the selectivity of 4-pyridoxic acid (PDA), homovanillic acid (HVA), glycochenodeoxycholate-3-sulphate (GCDCA-S) and taurine towards different renal transporters, including multidrug resistance-associated protein, and assessed the in vivo biomarker sensitivity towards the strong organic anion transporter (OAT) inhibitor probenecid at 500 mg every 6 h to reach close to complete OAT inhibition.

    PDA and HVA were substrates of the OAT1/2/3, OAT4 (PDA only) and multidrug resistance-associated protein 4; GCDCA-S was more selective, having affinity only towards OAT3 and multidrug resistance-associated protein 2. Taurine was not a substrate of any of the investigated transporters under the in vitro conditions tested. Plasma exposure of PDA and HVA significantly increased and the renal clearance of GCDCA-S, PDA and HVA decreased; the magnitude of these changes was comparable to those of known clinical OAT probe substrates. PDA and GCDCA-S were the most promising endogenous biomarkers of the OAT pathway activity PDA plasma exposure was the most sensitive to probenecid inhibition, and, in contrast, GCDCA-S was the most sensitive OAT biomarker based on renal clearance, with higher selectivity towards the OAT3 transporter.

    The current findings illustrate a clear benefit of measuring PDA plasma exposure during phase I studies when a clinical drug candidate is suspected to be an OAT inhibitor based on in vitro data. Subsequently, combined monitoring of PDA and GCDCA-S in both urine and plasma is recommended to tease out the involvement of OAT1/3 in the inhibition interaction.

    EudraCT number 2016-003923-49.

    EudraCT number 2016-003923-49.

    We aimed to compare the clinical characteristics and outcomes of bloodstream infections (BSI) in cancer patients presenting febrile neutropenia with and without HIV infection, and analyze the prognostic factors for mortality.

    BSI episodes in febrile neutropenic patients following chemotherapy were prospectively collected (1997-2018). A case (HIV-infected)-control (non-HIV-infected) sub-analysis was performed (12 ratio), matching patients by age, gender, baseline disease, and etiological microorganism.

    From 1755 BSI episodes in neutropenic cancer patients, 60 (3.4%) occurred in those with HIV. HIV characteristics 51.7% were men who have sex with men; 58.3% had<200 CD4; 51.7% had a detectable HIV-1 RNA viral load before the BSI episode; 70.0% met AIDS-defining criteria; and 93.3% were on antiretroviral therapy, with a protease inhibitor-based regimen being the most common (53.0%). HIV-infected patients were younger, more frequently male and more commonly presenting chronic liver disease (p<0.001 for, and experience higher mortality. However, HIV infection by itself was not associated with mortality.

    Postherpetic neuralgia (PHN) is the most common complication of herpes zoster. Methylene blue (MB) is an inhibitor of nitric oxide synthesis with potentially analgesic and anti-inflammatory properties. Studies have demonstrated that thoracic paravertebral single MB injection is effective in treating chronic pain. However, there are rare reports of the efficacy of continuous thoracic paravertebral infusion of MB for pain management in PHN patients. The purpose of this study was to evaluate the therapeutic effects of continuous thoracic paravertebral infusion of MB on PHN.

    A total of 104 PHN patients were randomly divided into two groups the control group (continuous thoracic paravertebral infusion of 5% lidocaine in a total volume of 300ml) and the MB group (continuous thoracic paravertebral infusion of 5% lidocaine plus 0.2% MB in a total volume of 300ml). All patients were evaluated using the Numerical Rating Scale (NRS), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), 36-Item Shorsion with MB is a safe and effective therapy for PHN. Continuous infusion with MB can significantly reduce pain intensity, improve pain-related depression, increase quality of life, and decrease the amount of rescue medicine with no serious adverse complications.

    Ultrasound-guided continuous thoracic paravertebral infusion with MB is a safe and effective therapy for PHN. Continuous infusion with MB can significantly reduce pain intensity, improve pain-related depression, increase quality of life, and decrease the amount of rescue medicine with no serious adverse complications.

    The tick-borne protozoa piroplasms, including Theileria and Babesia, are the cause of substantial economic losses to the livestock industry. However, in southern Qinghai province, China, there are limited information on the molecular characteristics of piroplasms. This study therefore aimed at determining the prevalence and genetic diversity of piroplasms.

    In order to detect piroplasms, we examined 330 yaks and 236 Tibetan sheep blood samples by nested PCR. The differences in piroplasms prevalence in relation to different risk factors was analyzed using SPSS 26. Phylogenetic analysis based on 18S rRNA sequences was inferred using MEGA 7.

    During this study, Theileria spp. were detected in 33.6% (111/330) of yaks and 94.1% (222/236) of Tibetan sheep, but no Babesia was identified. Importantly, a comparison study revealed that T. ovis infection was highly prevalent in sheep (94.1%) but infrequent in yaks (6.1%), while T. sinensis was host-specific to yaks with an infection rate of 27.6%. In addition, male of Theileria in China.

    To our knowledge, this is the first report of T. sinensis in Qinghai region. In addition, high prevalence of the generally sub-clinical T. ovis in sheep indicates extensive exposure to ticks and transmission of tick-borne pathogens with a significant economic impact. This study provides insights into the distribution and genetic diversity of Theileria in China.

    Diagnostic accuracy of malaria is critical for early treatment, control, and elimination of malaria, especially in war-affected malaria-endemic areas. Microscopic detection of Plasmodium species has been the gold standard in remote malaria-endemic regions. However, the diagnostic accuracy is still questioned, especially in discriminating mixed and submicroscopic parasitic levels. This study was designed to evaluate the diagnostic performance of microscopic examination against nested PCR analysis in war-torn malaria-endemic Federally Administered Tribal Areas (FATA) of Pakistan.

    Venous blood samples were collected from symptomatic patients for microscopic examination and nested PCR analysis from January 2016-December 2016 from five Agencies (Bajaur, Mohmand, Khyber, Orakzai and Kurram Agency) and four Frontier Regions (Peshawar, Kohat, Bannu, and Dera Ismail Khan Frontier Region) of FATA. Malaria-positive isolates were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ificity observed in nested PCR make this molecular tool a useful technique for monitoring, controlling, and eliminating malaria-endemic regions.

    Toxoplasma gondii is an apicomplexan parasite that exhibits distinct strain-related virulence patterns in mice. It can induce hepatic inflammation. The present study investigated MicroRNA-155 (miRNA-155) expression and butyrylcholinesterase (BChE) activity in the liver tissue of mice infected with virulent and avirulent strains of T. gondii.

    Mice groups included Group (A), uninfected controls; Group (B), infected with T. gondii avirulent strain (ME-49) and euthanized 7, 27, 47, or 67days post-infection (pi); Group (C), infected by T. gondii virulent strain (RH) and euthanized 7days pi; and Group (D), infected by T. gondii virulent strain (RH), treated 24h pi with sulfamethoxazole-trimethoprim (150mg/Kg/day and 30mg/Kg/day, respectively) and euthanized 5, 10, or 20days pi. miRNA-155 expression was estimated in the liver tissue using the reverse transcription real-time polymerase chain reaction and the ΔΔC

    method. BChE activity was estimated in liver homogenates by Ellman’s colorimetric method. Liver sections were examined histopathologically.

    revealed a significant elevation in miRNA-155 expression and a significant reduction of BChE activity in all the infected untreated groups compared to the uninfected mice. In group B, the maximum upregulation of miRNA-155 expression and the least reduction in BChE activity were detected 7days pi. In group D, complete restoration of normal levels occurred 20days pi. Liver sections showed distinct histopathological patterns with detection of intracellular tachyzoites in group B.

    miRNA-155 and BChE play a role in regulating host-parasite interaction in toxoplasmosis and may contribute to the pathogenesis of T. gondii induced hepatic damage.

    miRNA-155 and BChE play a role in regulating host-parasite interaction in toxoplasmosis and may contribute to the pathogenesis of T. gondii induced hepatic damage.

    Giardia intestinalis is a worldwide parasite. Drugs used for the treatment of giardiasis are metronidazole, albendazole and nitazoxanide. The development of drug resistance is an obstacle to the effective treatment. Resistance mechanisms in some parasites involve the participation of ATP-binding cassette (ABC) transporter superfamily.

    To find if the ATP-binding cassette genes are overexpressed in trophozoites treated with albendazole or nitazoxanide.

    A search for ATP-binding cassette genes in Giardia sequence database (GiardiaDB) was done and six genes were selected. Trophozoites treated with albendazole or nitazoxanide and the expression of these six ABC genes was quantitated by real-time RT-PCR. The ABC-C1 gene was selected, and a fragment cloned. The ABC-C1 protein was expressed, and polyclonal antibodies were elicited in mice to detect the protein in treated trophozoites, finally a docking analysis was performed for ABC-C1 and tizoxanide interaction.

    Bioinformatics analysis showed that the ATP-binding cassette (ABC) topology is present in the six proteins. The qRT-PCR revealed that the ABC-C1 gene was overexpressed in cells incubated with nitazoxanide or albendazole. Confocal analysis showed that ABC-C1 protein levels increased in trophozoites with both treatments but was higher with nitazoxanide. The mark was detected heavily in the periphery of the cells. Using a docking analysis, it was found that the nitazoxanide metabolite, tizoxanide was docked close to the ATP-binding region as well as in the exit tunnel, located in the transmembrane region.

    These findings in Giardia intestinalis, support the possible role of ABC-C1 in drug efflux.

    These findings in Giardia intestinalis, support the possible role of ABC-C1 in drug efflux.Mining is one of the main activities that drive the economy of Brazil. Mining activity is associated with risk of contamination of environment and local fauna by metals. Amphibians have a life cycle that requires a transition between aquatic and terrestrial environments, increasing their vulnerability to metal contamination in the water and substrate. Metals are ubiquitous, with high bioaccumulative and biomagnifying potential, and may lead to immune and endocrine disruption. In this study, we analyzed two different components of the innate immune response, bacterial killing ability (BKA) and phytohemagglutinin edema (PHA), and two stress biomarkers, corticosterone plasma levels (CORT) and the neutrophil to lymphocyte ratio (NL), of toads (Rhinella diptycha) living in places contaminated by metals. Blood samples were collected pre- and post-restraint (1h), followed by an immune challenge with PHA and tissue collection (liver, spleen, and kidneys). Toads liver metal bioaccumulation did not correlate with the immune response or stress biomarkers. Post-restraint, animals had increased CORT and reduced BKA, independently of the collection site, and these variables were not correlated with liver metal bioaccumulation. Interestingly, toads with the larger spleen (immune organ) showed increased NL post-restraint and greater edema after the PHA challenge. Our results indicate that toads living in metal-contaminated environments responded to acute stressor, activating the hypothalamic-pituitary-interrenal axis and the immune response. Keep tracking the physiological variables of these animals and the presence of metals in the environment and tissues should provide valuable health status indicators for the population, which is vital for proposing amphibian conservation strategies in these areas.Human immunodeficiency virus-1 (HIV-1) infection remains to be one of the major threats throughout the world. Many researchers are working in this area to find a cure for HIV-1. The group of the FDA approved drugs which are currently used against HIV-1 in the clinical practice include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors (InIs), and protease inhibitors (PIs). Fixed dose combinations (FDCs) of these drugs are available and are used as per the anti-retroviral therapy (ART) guidelines. Despite these, unfortunately, there is no cure for HIV1 infection to date. The present review is focused upon describing the importance of a post-transcriptional regulatory protein „Rev”, responsible for latent HIV-1 infection as a possible, and promising therapeutic target against HIV-1.

    The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19.

    We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants.

    There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3.03], p = 0.014; I

    90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), non-steroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5.05], p = 0.46; I

    99.7%).

    This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility.

    CRD42020224286.

    CRD42020224286.Frontotemporal dementia is a heterogeneous spectrum of neurodegenerative disorders. The neuropathological inclusions are tau proteins, TAR DNA binding protein 43 kDa-TDP-43, or fused in sarcoma-ubiquitinated inclusions. Genetically, several autosomal mutations account for the heritability of the disorder. Phenotypically, frontotemporal dementia can present with a behavioral variant or a language variant called primary progressive aphasia. To date, there are no approved symptomatic or disease-modifying treatments for frontotemporal dementia. Currently used therapies are supported by low-level of evidence (mostly uncontrolled) studies. The off-label use of drugs is also limited by their side-effect profile including an increased risk of confusion, parkinsonian symptoms, and risk of mortality. Emerging disease-modifying treatments currently target the progranulin and the expansion on chromosome 9 open reading frame 72 genes as well as tau deposits. Advancing our understanding of the pathophysiology of the disease and improving the design of future clinical trials are much needed to optimize the chances to obtain positive outcomes.

    Patients with esophageal squamous cell carcinoma (SCC) have limited treatment options. Blocking transforming growth factor-β (TGFβ), which can be overexpressed in these tumors, may enhance responses to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGFβ receptor II (TGFβRII) (a TGFβ „trap”) fused to a human IgG1 monoclonal antibody blocking PD-L1.

    The objective of this study was to investigate the safety and efficacy of bintrafusp alfa in Asian patients with pretreated, PD-L1-unselected esophageal SCC.

    In a phase 1 study, Asian patients with pretreated esophageal SCC received bintrafusp alfa 1200mg every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was safety/tolerability with a goal of exploring clinical activity.

    By the database cutoff of August 24, 2018, 30 patients (76.7% had two or more prior anticancer regimens) received bintrafusp alfa for a median of 6.1 weeks; two remained on treatment. Nineteen patients (63.3%) had treatment-related adverse events, seven (23.3%) with grade 3/4 events, and there were no treatment-related deaths. The confirmed objective response rate (ORR) per independent review was 10.0% (95% confidence interval [CI] 2.1-26.5); responses lasted 2.8-8.3+ months. All responses occurred in immune-excluded tumors. Investigator-assessed confirmed ORR was 20.0% (95% CI 7.7-38.6). Median overall survival was 11.9 months (95% CI 5.7-not reached).

    Bintrafusp alfa demonstrated a manageable safety profile and efficacy in Asian patients with pretreated esophageal SCC.

    NCT02699515.

    NCT02699515.

    This study describes presenting clinical features and surgical techniques associated with successful repair of pediatric rhegmatogenous retinal detachment (RRD).

    This is a retrospective case series which involved 242 cases younger than 18years with new-onset RRD with descriptive statistics for the full group. Further exclusion established 168 cases that underwent surgery with minimum 3-month follow-up. Comparison of features associated with successful outcomes was analyzed using Chi-squared tests, logistic regression and univariate generalized equation models.

    We measured proportion of patients with BCVA ≤ 1.0 logMAR and/or an increase in final BCVA of 0.3 logMAR with respect to baseline and complete reattachment at final visit; 104 eyes (62%) achieved total reattachment, and 91 eyes (54%) achieved visual success. Absence of macular involvement, subtotal RRD and older age group (13-18) were associated with both success measures. There were higher visual and anatomic success rates with primary scleral bua lower rate of success than either SB or combined SB/PPV.Effective biomarkers aid in the early diagnosis and monitoring of breast cancer and thus play an important role in the treatment of patients suffering from the disease. Growing evidence indicates that alteration of expression levels of miRNA is one of the principal causes of cancer. We analyze breast cancer miRNA data to discover a list of biclusters as well as breast cancer miRNA biomarkers which can help to understand better this critical disease and take important clinical decisions for treatment and diagnosis. In this paper, we propose a pattern-based parallel biclustering algorithm termed Rank-Preserving Biclustering (RPBic). The key strategy is to identify rank-preserved rows under a subset of columns based on a modified version of all substrings common subsequence (ALCS) framework. To illustrate the effectiveness of the RPBic algorithm, we consider synthetic datasets and show that RPBic outperforms relevant biclustering algorithms in terms of relevance and recovery. For breast cancer data, we identify 68 biclusters and establish that they have strong clinical characteristics among the samples. The differentially co-expressed miRNAs are found to be involved in KEGG cancer related pathways. Moreover, we identify frequency-based biomarkers (hsa-miR-410, hsa-miR-483-5p) and network-based biomarkers (hsa-miR-454, hsa-miR-137) which we validate to have strong connectivity with breast cancer. The source code and the datasets used can be found at http//agnigarh.tezu.ernet.in/~rosy8/Bioinformatics_RPBic_Data.rar . Graphical Abstract.

    Stereotactic body radiotherapy (SBRT) is a consolidate treatment for inoperable early-stage lung tumors, usually delivered in single or multi-fraction regimens. We aimed to compare these two approaches in terms of local effectiveness, safety and survival.

    Patients affected by medically inoperable early-stage lung tumor were treated at two Institutions with two different schedules 70Gy in ten fractions (TF) (BED10 119Gy) or 30Gy in single fraction (SF) (BED10 120Gy).

    73 patients were treated with SBRT delivered with two biological equivalent schedules SF (44) and TF (29). The median follow-up was 34months (range 3-81months). Three-year Overall survival (OS) was 57.9%, 3-year cancer-specific survival (CSS) was 77.2%, with no difference between treatment groups. Three-year progression-free survival (LPFS) was 88.9% and did not differs between SF and TF. Overall, four cases (5.4%) of acute grade ≥ 3 pneumonitis occurred. No differences in acute and late toxicity between the two groups were detected.

    SF and TF seems to be equally safe and effective in the treatment of primary inoperable lung tumors especially for smaller lesion. The SF may be preferentially offered to reduce patient access to hospital with no negative impact on tumor control and survival.

    SF and TF seems to be equally safe and effective in the treatment of primary inoperable lung tumors especially for smaller lesion. The SF may be preferentially offered to reduce patient access to hospital with no negative impact on tumor control and survival.

    The aim of this study was to analyze the associations between perceived social support and sociodemographic variables on coping strategies.

    A prospective, cross-sectional, multicenter study was conducted in 404 women with resected, non-metastatic breast cancer. Participants completed questionnaires perceived social support (MSPSS), coping strategies (Mini-MAC), and psychological distress (BSI-18).

    Sociodemographic factors as age, education, and partnership status were associated with coping strategies. As for maladaptive strategies, hopelessness was more frequent in older people and lower educational level; fatalism in older and single people, and cognitive avoidance was associated with lower educational level. Suppor t from family, friends, and partners was associated with a greater fighting spirit. In contrast, high psychological distress (anxiety and depression) was associated with greater use of maladaptive strategies.

    Young people, a high level of education, having a partner, low psychological distress, and seeking social support were associated with the use of adaptive cancer coping strategies.

    Young people, a high level of education, having a partner, low psychological distress, and seeking social support were associated with the use of adaptive cancer coping strategies.Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma characterized by an alveolar or organoid arrangement of polygonal tumour cells separated by fibrovascular septa. A specific fusion gene [ASPS critical region 1 (ASPSCR1)-TFE3] was detected in ASPS. Despite being a slow-growing tumour without pain and dysfunction, ASPS is characterized by early metastasis, which leads to poor prognosis. Herein, we report a rare case of primary ASPS of the cheek harbouring ASPSCR1 (exon 7)-TFE3 (exon 5) fusion gene in a 21 year-old woman. This tumour was a well-circumscribed, smooth, round mass that was clinically suspected as a benign tumour. However, histologically, it was observed that the polygonal tumour cells were arranged in solid and alveolar growth patterns. Post-operative examination of the whole body excluded the possibility of metastasis at other sites. Thus, careful immunohistochemical and genetic analyses, as well as whole-body examination, demonstrated that the tumour was a primary ASPS of the cheek.Collision tumor is the occurrence of two histologically and morphologically distinct tumors within the same organ with no histological admixture. Collision tumors of the thyroid are extremely rare constituting  less then  1% of all thyroid tumors. Clinical profiles and pathological features of Medullary thyroid carcinoma (MTC) and Papillary thyroid carcinoma (PTC) presenting as Collision tumors of thyroid, diagnosed between 2009 and 2019, at a tertiary care cancer center were retrospectively analyzed. Collision tumors comprised 4.7% of all MTC cases diagnosed over 10 years. A total of 21 cases (11males, 11 females, MF = 1) were retrieved with the mean age of patients being 45.33 years (range 26-77 years). More than half of PTCs involved the right lobe of the thyroid (66.6%). About half (53.4%) of MTCs affected the left lobe. Imaging done pre-operatively failed to identify the smaller second tumor in 60% of the cases with both tumours in separate lobes. Pre-operative FNAC showed only MTC in all 8 cases in whicnce in our cohort is in favor of the „Chance theory” of co-occurrence. This diagnosis is important due to its therapeutic and prognostic implications.To evaluate molecular epithelial changes, we investigated whether a profile of survivin, cyclin dependent kinase inhibitor 2A (CDKN2A), epidermal growth factor receptor (EGFR), polo like kinase 1 (PLK1), p63, p40 (Δnp63 isoform), cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) proteins could predict malignant transformation. Different tissue segments (tumor adjacent epithelium; dysplasia and tumor) from a total of 109 patients were analyzed by immunohistochemistry. An increased expression of survivin (p  less then  0.001), PLK1 (p = 0.001), and p63 (p  less then  0.001) in parallel to reduced immunostaining of p40 (p  less then  0.001) and BCL2 (p = 0.029) was observed among the tissue segments analyzed. Our study revealed that survivin, PLK1, p63, p40 and BCL2 play a role in oral tumorigenesis and represent promising biomarkers able to recognize mesenchymal phenotype induction in the transition from nonmalignant cells to tumor cells. These results reveals critical interaction between survivin, PLK1, p63, p40 promising proteins during invasive carcinoma development.This article attempts to reconstruct some important features (structural patterns) of social relations in biblical discourse, which is the most significant source of regulation in the social world of not only Christian communities but also outside of them in both the public and private lives of believers. An analysis was conducted on the basis of the striving for power theory by Alfred Adler and Władysław Witwicki, and on the linguistic category model by Gun Semin and Klaus Fiedler. The focus was mainly on the analysis of the concept of power and domination, preferred emotions, and a sense of social closeness as important variables regulating the social world of biblical time. The obtained results are primarily important for pastoral psychology, religious education, and psychotherapy.Natural killer T (NKT)-cells with both T- and NK-cell antigens can be classified into αβ or γδ type according to the TCR gene expression. The WHO classification of lymphoid neoplasms did not further subdivide the above-mentioned NKT-cell malignancies according to the expression of these TCR types. γδ T-cells can be stimulated and expanded by Zoledronic acid, usually carrying Vγ9 Vδ2 TCR and various NK-associated receptors (NKR) such as CD56, CD94, CD158a, CD158b, CD161, etc. In contrast, αβ T-type NKT-cells are positive for Vα24 Vβ11 TCR. NKR positive γδ T-cells have clearly different features than the NKT-cells with Vα24 Vβ11 TCR type, αβ NKT. NKT-cells carrying γδ TCR should be classified and named as γδ NKT-cells to distinguish the cells explicitly from αβ NKT-cells.

    Crossed cerebellar diaschisis (CCD) has been widely studied in hemispheric stroke but is less characterized in epilepsy. In this study, we used

    F-FDG PET/CT to investigate the risk factors for CCD and its prognostic value for intractable epilepsy caused by focal cortical dysplasia (FCD).

    One hundred medically intractable epilepsy patients pathologically diagnosed with FCD postoperatively were included and classified into two groups CCD+ and CCD-. PET/CT images were analyzed qualitatively by visual assessment and semi-quantitatively using the absolute asymmetry index (|AI|). Clinical factors, including age, sex, body mass index (BMI), age at seizure onset, epilepsy duration, seizure type, seizure frequency, electroencephalography (EEG) and brain magnetic resonance imaging (MRI), were retrospectively assessed from medical records. Follow-up outcomes were evaluated according to the Engel classification at 3, 6, 12, 24 and 36months postoperatively.

    Of the 100 patients, 77 (77.0%) were classified as CCD-, is of FCD patients at 12 months postoperatively.

    We report on the first identified cluster of the B.1.1.7 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the northeast of Italy.

    The cluster was recognized in January 2021 with an epidemiological started from the hospitalization of a 68-year-old man suffering from coronavirus disease 2019 (COVID-19) related pneumonia and we surprisingly found three families involved in the same cluster.

    We retrospectively rebuilt the pathway of infection and performed a virological analysis.

    This allow us to make clear the very high attack rate and the great infective capacity of this B.1.1.7 variant of SARS-CoV-2.

    This allow us to make clear the very high attack rate and the great infective capacity of this B.1.1.7 variant of SARS-CoV-2.

    Accurate placement of the needle is critical in interventions like biopsies and regional anesthesia, during which incorrect needle insertion can lead to procedure failure and complications. Therefore, ultrasound guidance is widely used to improve needle placement accuracy. However, at steep and deep insertions, the visibility of the needle is lost. Computational methods for automatic needle tip localization could improve the clinical success rate in these scenarios.

    We propose a novel algorithm for needle tip localization during challenging ultrasound-guided insertions when the shaft may be invisible, and the tip has a low intensity. There are two key steps in our approach. First, we enhance the needle tip features in consecutive ultrasound frames using a detection scheme which recognizes subtle intensity variations caused by needle tip movement. We then employ a hybrid deep neural network comprising a convolutional neural network and long short-term memory recurrent units. The input to the network is a ccs associated with needle tip motion and is more accurate than state-of-the-art methods. Therefore, it has the potential for improving needle tip localization in challenging ultrasound-guided interventions.

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