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1.
Sci Rep ; 14(1): 6855, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38514752

ABSTRACT

We evaluated the rate of autism spectrum disorder (ASD) in a group invited to a screening program compared to the rates in two groups who received usual care. The population eligible for screening was all children in Iceland registered for their 30-month well-child visits at primary healthcare centers (PHCs) from March 1, 2016, to October 31, 2017 (N = 7173). The PHCs in the capital area of Reykjavik were the units of cluster randomization. Nine PHCs were selected for intervention (invited group), while eight PHCs received usual care (control group 1). PHCs outside the capital area were without randomization (control group 2). An interdisciplinary team, including a pediatrician contributing with physical and neurological examination, a psychologist evaluating autism symptoms using a diagnostic instrument, and a social worker interviewing the parents, reached a consensus on the clinical diagnosis of ASD according to the ICD-10 diagnostic system. Children in the population were followed up for at least two years and 119 cases were identified. The overall cumulative incidence of ASD was 1.66 (95% confidence interval (CI): 1.37, 1.99). In the invited group the incidence rate was 2.13 (95% CI: 1.60, 2.78); in control group 1, the rate was 1.83 (95% CI: 1.31, 2.50); and in control group 2, the rate was 1.02 (95% CI: 0.66, 1.50). Although the rate of ASD was higher in the invited group than in the control groups, the wide confidence intervals prevented us from concluding definitively that the screening detected ASD more readily than usual care.


Subject(s)
Autism Spectrum Disorder , Humans , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/epidemiology , Iceland/epidemiology , Mass Screening , Random Allocation , Child, Preschool
2.
PLoS One ; 19(3): e0299151, 2024.
Article in English | MEDLINE | ID: mdl-38551936

ABSTRACT

BACKGROUND: The World Health Organization 2018 intrapartum guideline for a positive birth experience emphasized the importance of maternal emotional and psychological well-being during pregnancy and the need for safe childbirth. Today, in many countries birth is safe, yet many women report negative and traumatic birth experiences, with adverse effects on their and their families' well-being. Many reviews have attempted to understand the complexity of women's and their partners' birth experience; however, it remains unclear what the key dimensions of the birth experience are. OBJECTIVE: To synthesize the information from reviews of qualitative studies on the experience of childbirth in order to identify key dimensions of women's and their partners' childbirth experience. METHODS: Systematic database searches yielded 40 reviews, focusing either on general samples or on specific modes of birth or populations, altogether covering primary studies from over 35,000 women (and >1000 partners) in 81 countries. We appraised the reviews' quality, extracted data and analysed it using thematic analysis. FINDINGS: Four key dimensions of women's and partners' birth experience (covering ten subthemes), were identified: 1) Perceptions, including attitudes and beliefs; 2) Physical aspects, including birth environment and pain; 3) Emotional challenges; and 4) Relationships, with birth companions and interactions with healthcare professionals. In contrast with the comprehensive picture that arises from our synthesis, most reviews attended to only one or two of these dimensions. CONCLUSIONS: The identified key dimensions bring to light the complexity and multidimensionality of the birth experience. Within each dimension, pathways leading towards negative and traumatic birth experiences as well as pathways leading to positive experiences become tangible. Identifying key dimensions of the birth experience may help inform education and research in the field of birth experiences and gives guidance to practitioners and policy makers on how to promote positive birth experiences for women and their partners.


Subject(s)
Delivery, Obstetric , Parturition , Pregnancy , Humans , Female , Parturition/psychology , Delivery, Obstetric/psychology , Pain , Health Personnel , Family , Qualitative Research
3.
Gen Hosp Psychiatry ; 85: 229-235, 2023.
Article in English | MEDLINE | ID: mdl-37995481

ABSTRACT

OBJECTIVE: Exposure to adverse childhood experiences (ACEs) is a significant predictor for physical and mental health problems later in life, especially during the perinatal period. Prenatal common mental disorders (PCMDs) are well-established as a risk for obstetric interventions but knowledge on combined effects of multiple psychosocial risk factors is sparse. We aim to examine a comprehensive model of ACEs and PCMDs as risk factors for poor delivery and neonatal outcomes. METHOD: With structural equation modeling, we examined direct and indirect pathways between psychosocial risk and delivery and neonatal outcomes in a prospective cohort from pregnancy to birth in Iceland. RESULTS: Exposure to ACEs increased risk of PCMDs [ß = 0.538, p < .001, CI: 0.195-1.154] and preterm delivery [ß = 0.768, p < .05, CI: 0.279-1.007)]. An indirect association was found between ACEs and increased risk of non-spontaneous delivery [ß = 0.054, p < .05, CI: 0.004-0.152], mediated by PCMDs. Identical findings were observed for ACEs subcategories. CONCLUSION: ACEs are strong predictors for mental health problems during pregnancy. Both ACEs and PCMDs diagnosis are associated with operative delivery interventions and neonatal outcomes. Findings underscore the importance of identifying high-risk women and interventions aimed at decreasing psychosocial risk during the prenatal period.


Subject(s)
Adverse Childhood Experiences , Mental Disorders , Pregnancy , Infant, Newborn , Humans , Female , Mental Health , Prospective Studies , Mental Disorders/epidemiology , Risk Factors
4.
Animals (Basel) ; 13(17)2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37684997

ABSTRACT

Thirty controls (C) and 30 IBH-affected (T) Lusitano horses were evaluated. T horses were included based on anamnesis and physical examination, supported by questionnaires. All horses were submitted to skin tests, Intrademal (IDT) and Skin Prick Tests (SPT), on the neck with 14 specific allergens, 13 recombinant proteins (r-proteins) from Culicoides nubeculosus (Cul n) and Culicoides obsoletus (Cul o) salivary glands and Culicoides nubeculosus Whole Body Extract (Cul n WBE). Addicionally, a cluster of six T and six C horses were also tested with Cul n 3 and Cul n 4 produced in insect cells and barley, as well as E. coli produced Cul o 3 and Cul o WBE. Allergen concentrations were 10 µg/mL for IDT and 100 µg/mL for SPT, and wheal diameters assessed at 20 min, 6 and 48 h. IDTs were considered positive when wheal diameter was ≥50% of the histamine wheal and SPT's ≥ 0.9 cm. In vitro tests, allergen-specific serum IgE and sulfidoleukotriene (sLT) release assay were also carried out. Results showed that Cul n WBE, Cul n 7, 8, 9, Cul o1P and Cul o 2P were the best performing allergens for SPTs (p ≤ 0.0001) for the 1st allergen panel and Cul o WBE, Cul n 3 Bar and Cul n 4 Bac (p ≤ 0.05) for the 2nd, presenting a higher discriminatory diagnostic potential than IDTs, at a concentration of 100 µg/mL, with readings assessed at 20 min. Regarding in vitro tests overall, the sLT release assay performed best.

5.
PLOS Digit Health ; 2(8): e0000317, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37611020

ABSTRACT

New parents and their newborns are followed up after discharge either through home visits from midwives/nurses or using information and communication technology. This follow-up focuses on individual needs related to breastfeeding and infant feeding, practical advice on caring for babies, supporting and strengthening the new mother's knowledge and self-confidence concerning child development and parenting skills, and supporting the relationship between parents and baby. This systematic review aims to integrate available research results that describe new parents' experiences when health and care providers used telemedicine as a platform for follow-up after discharge from the childbirth department. This literature review was conducted following the PRISMA statement and was prospectively registered in PROSPERO CRD42021236912. The studies were identified through the following databases: AMED, Academic, EMBASE, Google Scholar, Ovid MEDLINE via PubMed, Cochrane database, and CINAHL. Results from these studies were compiled using thematic analysis. A total of 886 studies were identified. Screening resulted in eight studies that met the inclusion criteria. Thematic analysis produced the following themes: a) Flexibility and convenience of digital support, b) Digital literacy, c) Parents feeling safe with digital support, and d) Adequate substitute for physical meetings. New parents who live in a home environment with a relaxed atmosphere and around-the-clock digital support experience a sense of control, security, full attention, and encouragement. Digital follow up at home has proven effective because it can meet the support needs of new parents when necessary.

6.
Vet Immunol Immunopathol ; 253: 110502, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36272211

ABSTRACT

Insect bite hypersensitivity (IBH) is a seasonal dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides midges characterized by an imbalance of T-cell subsets. Iceland is free of the causative species but the prevalence of IBH in exported Icelandic horses is especially high. We have shown that intralymphatic (i.l.) vaccination with r-Culicoides allergens in Aluminum hydroxide (alum) and monophosphoryl lipid A (MPLA) adjuvants induces a desired Th1/regulatory T-cell response. The aim of this study was to compare i.l. to subcutaneous (s.c.) injection. Twelve healthy Icelandic horses were injected, i.l. or s.c., three times with four-week interval, using purified r-Culicoides allergens in alum/MPLA. Serum antibody levels and cytokine profile following in vitro re-stimulation of PBMC were analysed. Comparable allergen-specific IgG antibodies were induced following both routes of vaccinations. The antibodies showed similar capacity to block binding of IgE from IBH-affected horse to the allergens. Upon re-stimulation of PBMC, IL-10 was induced. Horses vaccinated i.l. produced more IFN-γ and less IL-4 as compared to the horses injected s.c., but the difference did not reach significance. It can be concluded that applying the simpler s.c. injection instead of i.l. to obtain a suitable immune response could be option in IBH immunotherapy.


Subject(s)
Ceratopogonidae , Horse Diseases , Hypersensitivity , Insect Bites and Stings , Horses , Animals , Insect Bites and Stings/prevention & control , Insect Bites and Stings/veterinary , Leukocytes, Mononuclear , Hypersensitivity/prevention & control , Hypersensitivity/veterinary , Allergens , Vaccination/veterinary , Immunoglobulin E
7.
Dalton Trans ; 51(34): 13119-13128, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-35975724

ABSTRACT

Organotin complexes are studied as promising alternatives to the anticancer drug cisplatin. We report two monoorganotin(IV) complexes based on a dibenzyl phosphinoyldithioformate (H-DBPTF) ligand, containing either bromide (Sn-DBPTF-1) or chloride (Sn-DBPTF-2) anions. The complexes were characterized by standard analytical techniques and the structural details of these complexes were elucidated by single crystal X-ray diffraction. Sn-DBPTF-1 was cytotoxic at IC50 <10 µg mL-1 against cancer cell lines A549 (lung cancer), Aspc-1 (pancreatic cancer), OVCAR-3 (ovarian cancer), T-47D (breast cancer) and HCT116 (colon cancer), and breast epithelial stem cell line D492. The non-tumorigenic breast epithelial cell line MCF-10 was less sensitive at IC50 = 22 µg mL-1. Sn-DBPTF-2 had limited cytotoxic effect at IC50 13-37 µg mL-1. Sn-DBPTF-1 induced apoptosis and double-strand DNA breaks. Cell cycle arrest in G2 occurred in HCT116 and accumulation in G1 in Aspc-1. The results indicate that the basic effect of Sn-DBPTF-1 is to induce DNA damage, leading to apoptosis and cell cycle arrest depending on the cell line.


Subject(s)
Antineoplastic Agents , Ovarian Neoplasms , Female , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis , Cell Line, Tumor , Drug Screening Assays, Antitumor , Tin/pharmacology
8.
PLoS One ; 17(8): e0273477, 2022.
Article in English | MEDLINE | ID: mdl-36018861

ABSTRACT

INTRODUCTION: The working environment abroad a ship is unique, with constant stimuli such as rolling of the vessel, noise, and vibration. Fishing industry is important for Icelandic economy, still the effect of seasickness-related symptoms on seamen´s health is not fully understood. Thus, the objective of this study is to explore the impact of seasickness-related symptoms, i.e., seasickness, seasickness symptoms and mal de débarquement on seaman´s health, and how their working environment may affect those factors. METHODS: Cross-sectional data was collected from 262 seamen answering questionnaire. Majority of the seamen participated while attending a compulsory course held by the Maritime Safety and Survival Training Centre. The majority of participants were men. A chi-square test was used to detect the difference between variables. RESULTS: The majority of seamen had experienced seasickness (87.8%) or mal de débarquement (85.8%). Having a history of tension headache (38.1%) and tinnitus (37.9%) was quite common. A total of 30.6% of the participants had been admitted to hospital once or more due to mishaps or accidents on land. DISCUSSION: Seasickness and seasickness symptoms together with mal de débarquement are common in Icelandic seamen. Working conditions at sea are demanding and seam to affect the seamen´s health both at sea and ashore, making further research needed.


Subject(s)
Motion Sickness , Cross-Sectional Studies , Female , Humans , Iceland , Male , Travel-Related Illness
9.
Autism ; 26(8): 2136-2150, 2022 11.
Article in English | MEDLINE | ID: mdl-35261293

ABSTRACT

LAY ABSTRACT: Professional guidance and support in response to first concerns appears to be an important predictor of the level of satisfaction with the detection process of autism in young children. In this study, we analyzed the views of 1342 family members, including 1278 parents, who completed an online survey form collecting information about their experience and satisfaction with the early detection of autism in their child. Specifically, we were interested in how specific experiences with the detection process relate to the satisfaction with it and whether we could identify important predictors of satisfaction. The detection process is an emotionally charged period for parents, often described as painful, chaotic, and lengthy. A better understanding of their experiences is important to take appropriate action to improve the detection process. In our sample, the level of satisfaction with the detection process varied greatly from one respondent to another. Among the different experiences we considered, whether or not respondents received professional guidance and support in response to first concerns explained most of this variation. We also found that difficulty finding information about detection services, lack of professional guidance and support in response to first concerns, having to find a diagnostic service on one's own, and longer delays between confirmation of concerns and first appointment with a specialist were experiences associated with a greater likelihood of being unsatisfied. The findings of this study highlight the importance of the parent-professional relationship in the detection process and have important practical implications for health administrations to improve the detection process.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Humans , Child, Preschool , Autistic Disorder/diagnosis , Autistic Disorder/psychology , Personal Satisfaction , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/psychology , Parents/psychology , Family
10.
J Autism Dev Disord ; 52(4): 1507-1522, 2022 Apr.
Article in English | MEDLINE | ID: mdl-33945117

ABSTRACT

The Modified Checklist for Autism in Toddlers, Revised with Follow-up was validated on a population sample in Reykjavik, Iceland. The participants (N = 1585) were screened in well-child care at age 30 months and followed up for at least 2 years to identify autism cases. The sensitivity, specificity, positive and negative predictive values were 0.62, 0.99, 0.72, and 0.99, respectively. True-positive children were diagnosed 10 months earlier than false-negative children. Autism symptom severity and the proportions of children with verbal and performance IQs/DQs < 70 were similar between groups. Although the sensitivity was suboptimal, the screening contributed to lowering the age at diagnosis for many children. Adding autism-specific screening to the well-child care program should be considered.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Autism Spectrum Disorder/diagnosis , Autistic Disorder/diagnosis , Checklist , Child, Preschool , Follow-Up Studies , Humans , Iceland , Infant , Mass Screening
11.
Scand J Caring Sci ; 36(3): 673-685, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34390257

ABSTRACT

BACKGROUND: Childhood sexual abuse (CSA) has widespread and long-lasting impact on women's lives and health. Increased knowledge and deeper understanding are needed of survivors' experiences of the childbearing process, health and motherhood. METHODS: In this phenomenological study, 16 in-depth interviews were conducted with nine female CSA survivors. The interviews were recorded, transcribed verbatim and thematically analysed. RESULTS: The overarching theme of the study is: 'more understanding is needed', which refers to the participants' experience that greater understanding is needed from health professionals of the long-term effects of CSA on childbearing women. Most of the women had suffered from poor health, especially chronic pain associated with fibromyalgia and gynaecological diseases. All of them had suffered mental health consequences particularly anxiety, depression and PTSD. The majority had experienced flashbacks to the violence and disassociation. Many had experienced miscarriages, had deviations from normal pregnancies and births, such as prolonged labour, caesarean sections, induction of labour, vacuum extraction, bleeding and exaggerated pregnancy problems, such as great nausea and pelvic pain. All but one had a negative experience in one of their births. All of them had experienced a lack of understanding in the healthcare system, perceived abuse of power and felt vulnerable in those situations. All of them had a strong need for a sense of control and participation in decision-making in the childbearing process. Most of them had experienced problems in bonding with their children and some have had difficulties touching them. All of them were in dire need of protecting their children from potential violence and many expressed a tendency to overprotect them. CONCLUSIONS: Healthcare professionals need to have more knowledge and greater understanding of how healthcare services can be improved so that CSA survivors can have a better experience of the childbearing process.


Subject(s)
Child Abuse, Sexual , Child , Child Abuse, Sexual/psychology , Delivery of Health Care , Female , Humans , Mental Health , Parturition/psychology , Pregnancy , Survivors/psychology
12.
Public Health Nurs ; 39(1): 270-278, 2022 01.
Article in English | MEDLINE | ID: mdl-34881465

ABSTRACT

BACKGROUND: Higher education should promote critical reflection and guide students towards international activities. In the Nordic countries public health nurse educational programmes are mostly based on guidelines issued by national educational authorities, which describe students' learning outcomes. AIM: The aim of this paper is twofold: to give an overview of public health nurse education and service in the Nordic countries and thereby discuss opportunities for collaboration within the programmes. DATA SOURCES AND COMPILATION OF DATA: National legislations for public health nurse education and services are used as data. Since all sources are written in the language of each country, all the authors wrote the parts that describe each countries conditions in English and contributed to the compilation of data. RESULTS: We found both similarities and differences in public health nurse education and services. Opportunities for collaboration between the programmes are discussed. CONCLUSION: Critical reflection by the public health nurse students can be enhanced by arranging collaboration projects, an exchange of clinical placement, and joint master projects. Collaboration among academic staff within the educational programmes, in education and research, have the potential to enhance quality both within public health nurse education and in developing the profession of public health nursing.


Subject(s)
Education, Nursing, Baccalaureate , International Educational Exchange , Nurses, Public Health , Students, Nursing , Humans , Public Health Nursing/education
13.
PLoS One ; 16(11): e0257819, 2021.
Article in English | MEDLINE | ID: mdl-34780496

ABSTRACT

BACKGROUND: Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis in horses incited by salivary allergens from Culicoides spp. IBH does not occur in Iceland, as the causative agents are absent, however a high prevalence is seen in horses exported to Culicoides-rich environments. AIMS: To study the natural course of sensitization to Culicoides allergens and identify the primary sensitizing allergen(s) in horses exported from Iceland utilizing a comprehensive panel of Culicoides recombinant (r-) allergens. METHOD: IgE microarray profiling to 27 Culicoides r-allergens was conducted on 110 serological samples from horses imported to Switzerland from Iceland that subsequently developed IBH or remained healthy. Furthermore, a longitudinal study of 31 IBH horses determined IgE profiles the summer preceding first clinical signs of IBH (TIBH-1), the summer of first clinical signs (TIBH) and the following summer (TIBH+1). In a group of Icelandic horses residing in Sweden, effects of origin (born in Iceland or Sweden) and duration of IBH (<4 years, 4-7 years, >7 years) on Culicoides-specific IgE was evaluated. Sero-positivity rates and IgE levels were compared. RESULTS: At TIBH, horses were sensitized to a median of 11 r-allergens (range = 0-21), of which nine were major allergens. This was significantly higher than TIBH-1 (3, 0-16), as well as the healthy (1, 0-14) group. There was no significant increase between TIBH and TIBH+1(12, 0-23). IBH-affected horses exported from Iceland had a significantly higher degree of sensitization than those born in Europe, while duration of IBH did not significantly affect degree of sensitization. CONCLUSION: Significant sensitization is only detected in serum the year of first clinical signs of IBH. Horses become sensitized simultaneously to multiple Culicoides r-allergens, indicating that IgE-reactivity is due to co-sensitization rather than cross-reactivity between Culicoides allergens. Nine major first sensitizing r-allergens have been identified, which could be used for preventive allergen immunotherapy.


Subject(s)
Allergens/immunology , Ceratopogonidae/immunology , Dermatitis, Atopic/immunology , Horse Diseases/immunology , Horses/immunology , Insect Bites and Stings/immunology , Animals , Cross Reactions , Dermatitis, Atopic/blood , Horse Diseases/blood , Iceland , Immunoglobulin E/blood , Insect Bites and Stings/blood , Longitudinal Studies , Protein Array Analysis/methods , Seasons , Sweden , Switzerland
14.
Vet Immunol Immunopathol ; 238: 110289, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34214910

ABSTRACT

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses, an IgE-mediated reaction to Culicoides midges. Causative Culicoides spp. are not indigenous in Iceland resulting in high prevalence of IBH in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. The aims were (i) to compare IgE levels in sera of IBH-affected horses born in Iceland (n = 47) with horses of the Icelandic breed (n = 23) and of other breeds (n = 27) born in Culicoides infested area; (ii) to investigate if barley could be a useful production system of allergens for IBH immunoassays. IgE binding in sera was tested by ELISA on two recombinant Culicoides allergens, rCul n 3 and rCul n 4, each produced in E. coli, insect cells and barley. Significantly more IgE was detected against all allergens in sera from IBH-affected compared to healthy horses. Icelandic-born Icelandic horses stand out with higher IgE levels against the allergens and higher area under the curve (AUC) on rCul n 4 as compared to the European-born horses. The barley and E.coli produced allergens had very similar performance in distinguishing between IBH-affected and healthy horses.


Subject(s)
Allergens/immunology , Ceratopogonidae/immunology , Dermatitis, Atopic/veterinary , Horse Diseases/immunology , Immunoglobulin E/blood , Insect Bites and Stings/immunology , Animals , Dermatitis, Atopic/immunology , Horses , Humans , Insect Proteins/immunology
15.
Allergy ; 76(4): 1147-1157, 2021 04.
Article in English | MEDLINE | ID: mdl-32780483

ABSTRACT

BACKGROUND: Allergy to bites of blood-sucking insects, including biting midges, can affect both human and veterinary patients. Horses are often suffering from an IgE-mediated allergic dermatitis caused by bites of midges (Culicoides spp). With the aim to improve allergen immunotherapy (AIT), numerous Culicoides allergens have been produced as recombinant (r-) proteins. This study aimed to test a comprehensive panel of differently expressed Culicoides r-allergens on a cohort of IBH-affected and control horses using an allergen microarray. METHODS: IgE levels to 27 Culicoides r-allergens, including 8 previously unpublished allergens, of which 11 were expressed in more than one expression system, were determined in sera from 347 horses. ROC analyses were carried out, cut-offs selected using a specificity of 95% and seropositivity rates compared between horses affected with insect bite hypersensitivity (IBH) and control horses. The combination of r-allergens giving the best performing test was determined using logistic regression analysis. RESULTS: Seropositivity was significantly higher in IBH horses compared with controls for 25 r-allergens. Nine Culicoides r-allergens were major allergens for IBH with seven of them binding IgE in sera from > 70% of the IBH-affected horses. Combination of these top seven r-allergens could diagnose > 90% of IBH-affected horses with a specificity of > 95%. Correlation between differently expressed r-allergens was usually high (mean = 0.69, range: 0.28-0.91). CONCLUSION: This microarray will be a powerful tool for the development of component-resolved, patient-tailored AIT for IBH and could be useful for the study of allergy to biting midges in humans and other species.


Subject(s)
Ceratopogonidae , Horse Diseases , Hypersensitivity , Insect Bites and Stings , Allergens , Animals , Horses , Humans , Hypersensitivity/veterinary , Immunoglobulin E , Insect Bites and Stings/veterinary , Microarray Analysis
16.
Inorg Chem ; 59(24): 18190-18204, 2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33249838

ABSTRACT

Water-soluble complexes are desirable for the aqueous detoxification of cyanide. Molybdenum complexes with α-amino acid and disulfide ligands with the formula K[(L)Mo2O2(µ-S)2(S2)] (L = leu (1), met (2), thr (3), and ser (4)) were synthesized in a reaction of [(DMF)3MoO(µ-S)2(S2)] with deprotonated α-amino acids; leu, met, thr, and ser are the carboxylate anions of l-leucine, l-methionine, l-threonine, and l-serine, respectively. Potassium salts of α-amino acids (leu (1a), met (2a), thr (3a), and ser (4a)) were prepared as precursors for complexes 1-4, respectively, by employing a nonaqueous synthesis route. The ligand exchange reaction of [Mo2O2(µ-S)2(DMF)6](I)2 with deprotonated α-amino acids afforded bis-α-amino acid complexes, [(L)2Mo2O2(µ-S)2] (6-8). A tris-α-amino acid complex, [(leu)2Mo2O2(µ-S)2(µ-leu + H)] (5; leu + H is the carboxylate anion of l-leucine with the amine protonated), formed in the reaction with leucine. 5 crystallized from methanol with a third weakly bonded leucine as a bridging bidentate carboxylate. An adduct of 8 with SCN- coordinated, 9, crystallized and was structurally characterized. Complexes 1-4 are air stable and highly water-soluble chiral molecules. Cytotoxicity studies in the A549 cell line gave IC50 values that range from 80 to 400 µM. Cyclic voltammetry traces of 1-8 show solvent-dependent irreversible electrochemical behavior. Complexes 1-4 demonstrated the ability to catalyze the reaction of thiosulfate and cyanide in vitro to exhaustively transform cyanide to thiocyanate in less than 1 h.


Subject(s)
Amino Acids/pharmacology , Antidotes/chemical synthesis , Antidotes/pharmacology , Cyanides/chemistry , Molybdenum/pharmacology , A549 Cells , Amino Acids/chemistry , Antidotes/chemistry , Cell Survival/drug effects , Cyanides/poisoning , Humans , Inhibitory Concentration 50 , Leucine/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Methionine/chemistry , Models, Molecular , Molecular Structure , Molybdenum/chemistry , Serine/chemistry , Solubility , Spectrophotometry, Infrared , Thiocyanates/chemistry , Threonine/chemistry , Water
17.
Vaccines (Basel) ; 8(2)2020 May 09.
Article in English | MEDLINE | ID: mdl-32397549

ABSTRACT

:Background: Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly Culicoides bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMVTT) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. Objective: the preclinical and clinical safety of the eIL-5-CuMVTT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMVTT-specific IgG in the serum and plasma of vaccinated and unvaccinated horses. Further, peripheral blood mononuclear cells (PBMCs) from the same horses were re-stimulated in vitro for the proliferation and IFN-γ production of specific T cells. In addition, we evaluated longitudinal kidney and liver parameters and the general blood status. An endogenous protein challenge was performed in murine IL-5-vaccinated mice. Results: The vaccine was well tolerated as assessed by serum and cellular biomarkers and also induced reversible and neutralizing antibody titers in horses and mice. Endogenous IL-5 stimulation was unable to re-induce anti-IL-5 production. The CD4+ T cells of vaccinated horses produced significantly more IFN-γ and showed a stronger proliferation following stimulation with CuMVTT as compared to the unvaccinated controls. Re-stimulation using E. coli-derived proteins induced low levels of IFNγ+CD4+ cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Conclusions: Vaccination using eIL-5-CuMVTT induces a strong B-cell as well as CuMVTT-specific T cell response without the induction of IL-5-specific T cell responses. Hence, B-cell unresponsiveness against self-IL-5 can be bypassed by inducing CuMVTT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses.

18.
Inorg Chem ; 59(11): 7644-7656, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32401019

ABSTRACT

Removal of cyanide as nontoxic thiocyanate under physiological conditions may serve as a catalytic detoxification route in vivo. Aqueous catalytic reaction conditions were explored where at the conditions employed the reaction proceeded to exhaustion in 1 h. The complex, syn-[Mo2O2(µ-S)2(S2)(DMF)3] 1, participates in a ligand exchange reaction of the dimethylformamide ligands and cyanide. Simultaneous sulfur abstraction reaction from the terminal disulfide group forms thiocyanate and terminal sulfido ligand. Respective reaction rates for the two reactions appear competitive where different products were isolated solely based on change of reaction temperature. The approach to determine the number of cyanide ligands participating in the ligand exchange reaction by varying the stoichiometry and reaction temperature led to identification and isolation of tetranuclear complexes 2 and 5 and dinuclear complexes 3, 4, and 6. A synthesized and fully characterized thiocyanate analog of 6 (7) supports spectroscopic characterization of 6. The tetranuclear anion, [Mo4O4(µ-S)6(CN)4]4-, 2, was crystallized from a reaction at ambient temperature. The dinuclear anion, [Mo2O2(µ-S)2(S)(CN)3]3-, 3, was crystallized from similar reaction conditions at lower temperature. The reaction yield of thiocyanate obtained at pH of 7.4 and at 9.2 as a function of time, for several ratios of cyanide, favors the sulfur abstraction reaction at elevated pH. The sulfur abstraction reaction is the first step in a proposed mechanism of the reaction of cyanide and thiosulfate to form thiocyanate and sulfite by 1.

19.
Int J Biol Macromol ; 160: 548-557, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32439452

ABSTRACT

Two new cationic chitosan derivatives were synthesized using a combination of Boc and TBDMS protection strategies. This included a series of six samples of the TMCNH2/TM derivative, where some of the amino groups were N,N,N-trimethylated and the remaining was in the primary state. A series of six samples of the TACin derivative, where some of the amino groups were N-acetylated with quaternary 2-(N,N,N-trimethylammoniumyl) acetyl group and the remaining fully N-acetylated, were also synthesized. The degree of substitution (DS) for quaternary amino groups in these series ranged from 0.06-0.89. TMCDM/TM derivatives with a mix of N,N,N-trimethylated and N,N-dimethylated groups were also synthesized according to a published procedure but in this case, it was more difficult to control the DS than with the TBDMS protection strategy. Broth microdilution assay revealed a markedly different structure-activity relationship (SAR) for the two derivatives. The activity for the TMC derivatives reached a plateau above 0.2-0.3 DS whereas the activity increased continuously with DS for TACin. The highest DS TMCNH2/TM was more active than the highest DS, TACin, against Gram-positive MRSA but less active against the Gram-negative P. aeruginosa.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Chitosan/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Pseudomonas aeruginosa/drug effects , Cations/chemistry , Microbial Sensitivity Tests/methods , Structure-Activity Relationship
20.
Scand J Caring Sci ; 34(1): 167-180, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31218722

ABSTRACT

INTRODUCTION: Although perinatal distress is acknowledged as a burdening condition for pregnant women, its effects on pregnancy are not well known. This study was conducted to increase knowledge regarding the effects of distress on pregnancy-related problems. The study also assessed women's need for sick leave and increased prenatal care due to distress, and the effects of weak social support and dissatisfaction with their partner relationships. METHODS: In total, 2523 women were screened for perinatal distress three times during pregnancy in this quantitative cohort study. Structured psychiatric interviews were conducted following the screening, with 562 of the participants. Data from participants' pregnancy records were also analysed. The study was conducted in primary healthcare centres in Iceland after receiving approval from the Icelandic National Bioethical Committee. The main outcome measures were pregnancy problems, sick leave issued and prenatal service needs. RESULTS: Data from 503 women were analysed. The perinatal distress group (PDG) was significantly more likely than was the nondistressed group (NDG) to experience fatigue, vomiting and pelvic pain after controlling for background variables. Distressed women who reported weak family support experienced symptoms of nausea and heartburn. The PDG needed more frequent prenatal care than did the NDG and was issued sick leave for up to 42 days longer. Dissatisfaction in the partner relationship and with the division of household tasks and childcare was strongly associated with distress, the development of complications and the need for sick leave. DISCUSSION: Identification of perinatal distress by midwives and other healthcare professionals is important, since distress may be linked to women's complaints of fatigue, vomiting, pelvic pain and need for prolonged sick leave, and additional prenatal care services will be needed. Perceived dissatisfaction in the partner relationship and with the division of household tasks should also form part of clinical practice and assistance provided.


Subject(s)
Health Services Needs and Demand , Personal Satisfaction , Pregnancy Complications , Sexual Partners , Sick Leave , Social Support , Cohort Studies , Female , Humans , Iceland , Pregnancy
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