Albuterol as an adjuvant in acute anticholinesterase pesticide poisoning: a randomized, placebo-controlled clinical trial.

Acute anticholinesterase pesticide poisoning is a serious clinical problem, particularly in developing countries. Atropine is the most acceptable treatment for acute anticholinesterase poisoning. However, it only stops fluid production. Albuterol is a beta-2 receptor agonist that can increase fluid removal and speed the return of effective oxygen exchange. This study aims to evaluate the safety and efficacy of nebulized albuterol as an adjuvant therapy in patients with acute anticholinesterase poisoning. This stratified block randomized, single-blinded, placebo-controlled, parallel-group clinical trial was conducted between November 2020 and October 2021. It enrolled 80 patients with acute anticholinesterase pesticide poisoning who were admitted to Tanta University Poison Control Center. Patients were allocated into two groups (40 patients each). The strata were based on the severity of poisoning (moderate and severe). Patients in group I received 10 mg of nebulized albuterol. Group II received an equivalent volume of nebulized normal saline. Additionally, standard treatment was provided to both groups. Outcomes included oxygenation, mortality, need for endotracheal intubation and mechanical ventilation, hospital stay duration, time to atropinization, and total doses of atropine and oxime. We found insignificant differences in sociodemographics, exposure characteristics, clinical manifestations, or routine laboratory tests between the studied groups. The median values of oxygen saturation by pulse oximetry were 99% in the albuterol moderate toxicity group and 98% in the control moderate toxicity group. Albuterol significantly improved oxygen saturation in moderate intoxicated patients (P = 0.039). Therefore, nebulized albuterol is a safe drug. Moreover, it may improve oxygenation in acute anticholinesterase pesticide poisoning.

Effect of Sofosbuvir on rats' ovaries and the possible protective role of vitamin E: biochemical and immunohistochemical study.

Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.

Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial.

BACKGROUND: Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. MATERIALS AND METHODS: NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. RESULTS: From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. CONCLUSIONS: Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab.

[Buprenorphine depot in opiate use disorder]. / Buprenorfinedepot bij een stoornis in het gebruik van opiaten.

BACKGROUND: Patients with opiate use disorder may be treated medicamentally with methadone and sublingual buprenorphine. However, also two forms of subcutaneous buprenorphine that can be administered weekly or monthly are available. AIM: To describe the effectiveness and the side effects of the buprenorphine depot. METHOD: Embase was searched and cross-references were sought in the included studies and previous reviews. RESULTS: Nine articles were included. One randomized study (n = 428) compared buprenorphine depot to the sublingual form, with the depot being more effective after 12-24 weeks. The other randomized study (n = 504) compared the depot with placebo. The depot was found to be effective. In two comparative non-blinded studies, no significant difference in abstinence was reported between the depot and sublingual administration. Medium-term effectiveness (16-52 weeks) was confirmed in five follow-up studies, in which the depot preparation proved both effective and well tolerated. CONCLUSION: The buprenorphine depot is described as promising in the international literature. However, there are still several uncertainties that make its prescription should be done with great caution.

Porous honeycomb film membranes enhance endothelial barrier integrity in human vascular wall bilayer model compared to standard track-etched membranes.

In vitro vascular wall bilayer models for drug testing and disease modeling must emulate the physical and biological properties of healthy vascular tissue and its endothelial barrier function. Both endothelial cell (EC)-vascular smooth muscle cell (SMC) interaction across the internal elastic lamina (IEL) and blood vessel stiffness impact endothelial barrier integrity. Polymeric porous track-etched membranes (TEM) typically represent the IEL in laboratory vascular bilayer models. However, TEM stiffness exceeds that of diseased blood vessels, and the membrane pore architecture limits EC-SMC interaction. The mechanical properties of compliant honeycomb film (HCF) membranes better simulate the Young's modulus of healthy blood vessels, and HCFs are thinner (4 vs. 10 µm) and more porous (57 vs. 6.5%) than TEMs. We compared endothelial barrier integrity in vascular wall bilayer models with human ECs and SMCs statically cultured on opposite sides of HCFs and TEMs (5 µm pores) for up to 12 days. Highly segregated localization of tight junction (ZO-1) and adherens junction (VE-cadherin) proteins and quiescent F-actin cytoskeletons demonstrated superior and earlier maturation of interendothelial junctions. Quantifying barrier integrity based on transendothelial electrical resistance (TEER), membranes showed only minor but significant TEER differences despite enhanced junctional protein localization on HCF. Elongated ECs on HCF likely experienced greater paracellular diffusion than blocky ECs on TEM. Also, larger populations of plaques of connexin 43 subunit-containing gap junctions suggested enhanced EC-SMC communication across the more porous, thinner HCF. Compared with standard TEMs, engineered vascular wall bilayers cultured on HCFs better replicate physiologic endothelial barrier integrity.

[Willingness to receive COVID-19 vaccinations among clinical psychiatric patients]. / Drempels tot vaccinatie bij kortdurend opgenomen patiënten.

BACKGROUND: Psychiatric patients have an increased risk of infection with SARS-CoV-2 and morbidity and mortality rates are higher. Willingness to get vaccinated against SARS-CoV-2 may be less compared to the general population. AIMS To gain more knowledge about the willingness to be vaccinated and about underlying arguments among clinical psychiatric patients. METHOD: We submitted a questionnaire to clinical psychiatric patients, in which we assessed the willingness to be vaccinated and presented a number of statements about vaccination. RESULTS: In total, 70 patients were invited to participate in this study of which 56 patients (80%) completed the questionnaires. The willingness to be vaccinated was 63%. Of the 56 patients included, 5 indicated to have had SARS-CoV-2 (9%) and 16 patients (29%) had been vaccinated. Patients who refused vaccination reported being afraid of side effects of the vaccine (28%) and long-term effects of vaccination on their health (25%). Furthermore, patients found it complicated to make a vaccination appointment. CONCLUSION: In this study the willingness to be vaccinated appears to be low. We recommend on the basis of this study that in order to improve the vaccination coverage among psychiatric patients, more attention should be paid to vaccination in the psychiatric wards.

[Somatoparaphrenia in a patient with schizophrenia and addiction problems: 'That arm is not mine, doctor']. / Somatoparafrenie bij een patiënt met schizofrenie en verslavingsproblematiek: 'Die arm is niet van mij, dokter'.

Somatoparaphrenia is a disorder of body perception, usually on the left side. One or both limbs are seen as foreign or as belonging to somebody else. In the literature this rare phenomenon has been described in patients with brain damage, usually due to an infarction or other lesion to the right parietal lobe. We describe a patient with schizophrenia and addiction problems who believed that his left forearm was not his, but rather belonged to a Spanish girl. An EEG and an MRI of the brain showed no abnormalities. Despite years of antipsychotic treatment, the delusion persisted. To rule out neurological causes we recommend auxiliary investigations in all patients with somatoparaphrenia. No evidence-based treatments are known for this monothematic delusion in the context of schizophrenia.

[Osteoporosis in androgen deprivation therapy: finding the balance between social and individual interests]. / Osteoporose bij androgeendeprivatie: afweging tussen maatschappij en individu.

Androgen deprivation therapy (ADT) is a libido-inhibiting medication that may be necessary to reduce recidivism in the treatment of paraphilic disorders, especially in those with a pedophilic disorder. However, there is a significant risk to develop osteoporosis while using ADT and thereby an increased risk to develop fractures. These risks and benefits must be carefully weighed in the treatment of these patients. We describe a case in which this dilemma is further explained and clarified. We recommend to request a second opinion and a structured risk assessment. If the risk for recidivism remains increased, despite psychotherapeutic interventions, we advise to suspend further rehabilitation into society, and let the reduction of the risk of recidivism prevail over the wishes of the patient.

Clinical Impact of Circulated miR-1291 in Plasma of Patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC): Implication on Glypican-3 Expression.

PURPOSE: Liver cirrhosis (LC) is considered to be the end stage of chronic hepatopathies which may lead to hepatocellular carcinoma (HCC). Glypican-3 is one of the most promising serum markers for HCC. Abnormal expression of miRNAs may participate in cancer development and progression. In this study, we aimed to evaluate the relation between the expression of miR-1291 and GPC3 production as a non-invasive tool to differentiate patients with LC and HCC. METHODS: HCV patients (100) were divided into two groups; HCC (I) and LC (II). Fifty hepatitis-free subjects served as the control group (III). Expression of serum GPC3 was performed by enzyme-linked immunosorbent assay, and expression of circulating miR-1291 was performed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Serum levels of GPC3 were significantly elevated in patients with HCC compared with the LC group. Both groups have increased GPC3 levels in relation to healthy controls. Serum GPC3 levels with a cutoff value of 619.5 pg/ml had a 50% sensitivity and 89.3% specificity while alpha-fetoprotein (AFP) with a cutoff value of 8.5 ng/ml had a higher sensitivity (87.5%) and specificity (100%) in the detection of HCC. The primary use of both markers improved the specificity to 100%. miR-1291 was significantly upregulated in HCC and LC patients compared with control subjects. CONCLUSIONS: Our findings might indicate that miR-1291 exert oncogenic effects in hepatic carcinogenesis through positive regulation of GPC3 expression. We propose that GPC3 overexpression and its associated oncogenic effects are linked to the upregulation of miR-1291 in HCV patients.

[The efficacy of baclofen in alcohol dependence]. / De effectiviteit van baclofen bij de stoornis in alcoholgebruik.

BACKGROUND: In the past years numerous studies have investigated the efficacy of baclofen for alcohol dependence. After publication of several reviews a number of new randomized controlled trials have been published. Two recent meta-analyses, based on largely the same studies, reported contrary results. One meta-analysis showed a positive effect on time to relapse and abstinence at endpoint. The other meta-analysis did not show an effect on the primary outcome measures.
AIM: To clarify the clinical relevance of the effect of baclofen on alcohol use in patients with a disorder in the use of alcohol, in the light of the positive and the negative meta-analysis.
METHOD: A systematic literature search using Medline, Embase and PsycINFO (Prisma guideline).
RESULTS: We found 16 randomized controlled trials in which the effect of baclofen was studied. Seven of them showed a significant positive effect of baclofen on (one or more of the) primary outcome measures.

[Smoke-free psychiatric hospitals and the role of aggression: a systematic review]. / Is er een risico op toename van agressie bij een rookvrije ggz? Een literatuurstudie.

AIM: To provide an overview of the literature on transitions towards smoke-free psychiatric hospitals and the risk of aggression.
METHOD: A systematic search was made in medline, Embase and Psycinfo. Studies were included if they reported data on: a smoke-free intervention in a psychiatric hospital or ward, the number of aggressive incidents, and seclusions or prn drugs.
RESULTS: A total of 17 studies matched the inclusion/exclusion criteria; 5 reported a decrease in the number of aggressive incidents after implementation of a smoke-free ward, 7 showed an increase in the number of incidents, and 5 studies reported no differences. Heterogeneity between the studies was high with respect to the definition and implementation of the intervention, the definition and measurement of aggression, study design, length of follow-up, and the sample size.
CONCLUSION: These findings suggest that, after changing the policy towards a smoke-free psychiatric hospital, the risk of aggression is limited. However, several precautions related to the preparation and implementation of this transition seem to be essential. The results support further investment in the implementation of smoke-free psychiatric hospitals in the Netherlands, while maintaining safety.

[The pharmacological treatment of PTSD and alcohol use disorder: a systematic literature review]. / De medicamenteuze behandeling van PTSS en een comorbide stoornis in alcoholgebruik: een systematische literatuurstudie.

BACKGROUND: The co-occurrence of PTSD and alcohol use disorder (AUD) is common. Therefore, it is important to know which treatments are effective for the group of patients suffering from both disorders.
AIM: To explore the evidence of medical treatment options for PTSD and AUD.
METHOD: We systematically searched the literature using MEDLINE, Embase and psycINFO (PRISMA guideline).
RESULTS: Ten studies were included of which 9 were randomised controlled trials (RCT). Only one or a few RCTs examined several drugs. The combination of sertraline, naltrexone and disulfiram showed the biggest effect, although the results were limited and partly contradictory.
CONCLUSION: At the moment, there is little evidence for a clear pharmacological preference for the treatment of both PTSD and AUD. Based on the current studies there is, although limited, most evidence for the combination of naltrexone and sertraline or monotherapy with disulfiram. Further research is necessary in order to adequately treat this double diagnosis.

[Efficacy of integrated dual disorder treatment for dual disorder patients: a systematic literature review]. / Geïntegreerd behandelen van patiënten met dubbele diagnose met integrated dual diagnosis treatment (IDDT): systematische literatuurstudie.

BACKGROUND: Dual diagnosis (substance use disorder combined with a comorbid mental illness) is a common problem. One of the methods to treat this is integrated dual diagnosis treatment (IDDT). IDDT consists of the simultaneous, integrated application of different treatment components. Their efficacy, however, has only been studied separately. As a result, the effectiveness of the IDDT program as a whole remains unclear. AIM: To evaluate the scientific evidence relevant to the effectiveness of IDDT in dual diagnosis patients. METHOD: A systematic literature review using MEDLINE, Embase and PsycINFO (Prisma guideline). RESULTS: Six studies were found: a randomised controlled study (RCT), two non-randomised controlled studies, and three uncontrolled pre-post studies . There was a notably large diversity in outcome measures. The results differed significantly, including some studies concluding a significant (additional) effect, while others concluded that there was no indication of a significant effect of IDDT. CONCLUSION: In clinical practice, IDDT is recommended and chosen frequently as the treatment for patients with dual diagnosis. However, it is remarkable how limited and unthorough the research is pertaining to the effects of the full IDDT program on dual diagnosis.

Effect of human umbilical cord blood derived CD34+ hematopoietic stem cell on the expression of Wnt4 and P53 genes in a rat model of hepatocellular carcinoma.

BACKGROUND AND AIM OF THE WORK: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy. Chronic liver injuries as chronic hepatitis C and hepatitis B viruses, aflatoxins consumption and nonalcoholic fatty liver disease are well-established causes of HCC. HCC is associated with a series of molecular changes, as alternation in glypican-3, P53 expression and Wnt/ß-catenin pathway. Hepatic cancer progenitor cells could contribute to HCC development. This research aimed to study the effectiveness of human CD34+ hematopoietic stem cell on Wnt4 and P53 genes expression, histopathological grading and hepatic progenitor cells percentage in HCC rat model. MATERIALS AND METHODS: HCC was induced in the experimental group of outbred Sprague Dawley rats by administration of 50 mg/L N-nitroso-Di-Ethylamine (DEN) in drinking water for 15 weeks. Forty-six animals were used in total, they were initially subdivided into two groups; control (n = 6) and experimental (n = 40), the latter consisting of 4 DEN-unaffected, 6 DEN-lethalities and 30 surviving DEN-animals with elevated AFP. These 30 animals with elevated AFP were then subdivided into a new HCC control group (n = 15) and the stem cell treated group (n = 15). The latter group was injected with CD34+ human hematopoietic stem cell (1 × 106 cells/rat) in the rat's tail vein. Cyclosporine A (10 mg/kg) was injected intraperitoneal, starting 24 h before human stem cell transplantation. After 20 weeks passing since the beginning of the experiment, all rats were sacrificed and liver specimens were subjected to histopathological examination, RT-PCR in order to examine Wnt4 and P53 gene expression and flow cytometry to measure hepatic progenitor OV6 positive cells percentage. RESULTS: The saline-treated HCC group (with prior 15 week DEN exposure) showed higher levels of wnt4 and p53 gene expression (1.59 and 1.36 fold, respectively) and increased percentage in OV6+ progenitor cells (+4.9% in absolute terms) compared to saline-treated controls (p < 0.01, ANOVA). Compared with the saline HCC-group, transplantation with CD34+ human hematopoietic stem cells produced a further increase in the levels of wnt4 (+19.4%) and p53 gene expression (+53%), a 2-fold increase in the percentage of cancer progenitor cells and increased HCC pathology grading (all p < 0.01). The positive correlation between p53 and HCC grade (Spearman rho +0.73, p < 0.05) and negative correlation between wnt and OV6+% levels (rho -0.65, p < 0.05) in the saline-HCC group were not observed in the CD34+ HCC group. CONCLUSIONS: Human CD34+ cells transplantation has a deteriorating effect on HCC.

[Staging and profiling of patients with dual disorders]. / Stagering en profilering van patiënten met een dubbele diagnose.

BACKGROUND: Although there is a great need for staging and profiling in psychiatry, no-one has so far devised a staging and profiling model to aid diagnosis and treatment. AIM: To devise a basic staging and profiling strategy that can be used to treat patients suffering from both substance abuse disorder and a psychiatric disorder. METHOD: On the basis of existing staging model for addiction, we explore how staging could also be useful for the treatment of comorbidity in psychiatry. RESULTS: Since there is hardly any evidence of the use of staging for this kind of comorbidity, we present a staging model that might help to provide a solution. To the described stages we add a recommended treatment setting or treatment intensity. CONCLUSION: Further research is needed to ascertain whether the staging model that we have presented will lead to improvements in the prognosis and treatment of patients with dual disorders referred to Dutch psychiatrists.

Cognitive Cost of Using Augmented Reality Displays.

This paper presents the results of two cognitive load studies comparing three augmented reality display technologies: spatial augmented reality, the optical see-through Microsoft HoloLens, and the video see-through Samsung Gear VR. In particular, the two experiments focused on isolating the cognitive load cost of receiving instructions for a button-pressing procedural task. The studies employed a self-assessment cognitive load methodology, as well as an additional dual-task cognitive load methodology. The results showed that spatial augmented reality led to increased performance and reduced cognitive load. Additionally, it was discovered that a limited field of view can introduce increased cognitive load requirements. The findings suggest that some of the inherent restrictions of head-mounted displays materialize as increased user cognitive load.

Transendothelial migration of human umbilical mesenchymal stem cells across uterine endothelial monolayers: Junctional dynamics and putative mechanisms.

INTRODUCTION: During pregnancy, fetal stem cells can transfer to the maternal circulation and participate in tissue repair. How they transmigrate across maternal endothelial barriers and whether they can subsequently influence maternal endothelial integrity is not known. METHODS: Mesenchymal stem cells (WJ-MSC) were isolated from Wharton's jelly and their interactions with human uterine microvascular endothelial cell (HUtMEC) monolayers, junctional occupancy and expression/phosphorylation of vascular endothelial (VE)- cadherin and vascular endothelial growth factor (VEGF-A) secretion was studied over 48h by real time, confocal microscopy, immunoblotting and ELISA. RESULTS: WJ-MSC displayed exploratory behaviour with interrogation of paracellular openings and spreading into the resultant increased gaps followed by closing of the endothelium over the WJ-MSC. 62% of added cells crossed within 22h to sub-endothelial niches. There was a concomitant loss of junctional VE-cadherin in HUtMEC followed by a full return and increased VE-cadherin expression after 22h. During early hours, VE-cadherin showed a transient phosphorylation at Tyrosine (Tyr)-685 when VEGF-A secretion were high. From 16 to 22h, there was increased de-phosphorylation of Tyr-731. Anti-VEGF-A blocked Tyr-685 phosphorylation but not the decrease in P-Tyr731; this partially inhibited WJ-MSC transmigration. DISCUSSION: Fetal WJ-MSC can traverse uterine endothelial monolayers by mediating a non-destructive paracellular pathway. They can promote junctional stability of uterine endothelium from the sub-endothelial niche. Mechanistically, WJ-MSC induces VEGF-dependent phosphorylation events linked with paracellular permeability and VEGF-independent de-phosphorylation events associated with leukocyte extravasation. Our data also allows consideration of a possible role of fetal MSC in mature functioning of the uterine vasculature needed for optimal utero-placental perfusion.

[A disulfiram-alcohol reaction after inhalation of a salbutamol aerosol: a plausible interaction?]. / Een disulfiram-alcoholreactie na gebruik van salbutamolaerosol; een plausibele interactie?

An asthmatic patient (male, aged 47) being treated for his alcohol dependence complained of experiencing mild symptoms of disulfiram-alcohol reaction after using of pressurised metered-dose inhaler containing ethanol. It has been reported in the literature that the disulfiram-alcohol reaction may occur after a patient has been exposed to only minimal amounts of ethanol. This is why, in daily practice, physicians are generally reluctant to prescribe preparations containing ethanol and why they usually switch patients to an alternative. However, close evaluation of the biopharmaceutical and pharmacokinetic aspects of ethanol suggests that subjective disulfiram-alcohol reactions following the use of inhalers containing ethanol cannot be explained rationally from a clinical pharmacological perspective.