1.
Johansson, Åsa, et al.
(author)
Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification
2023
In: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 294:4, s. 378-396
Research review (peer-reviewed) abstract
Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
2.
Ebrahimi, Sheida, et al.
(author)
Application of PET/MRI in Gynecologic Malignancies
2024
In: Cancers. - : MDPI. - 2072-6694. ; 16:8
Research review (peer-reviewed) abstract
Simple Summary This article reviews the value of Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in evaluating female pelvic cancers. It also provides a comparative analysis of PET/MRI with other imaging modalities in the context of female pelvic malignancies and outlines their respective strengths and limitations. The aim of this narrative review is to introduce to clinicians up and coming technology and how it may be valuable to their assessment of female pelvic cancers.Abstract The diagnosis, treatment, and management of gynecologic malignancies benefit from both positron emission tomography/computed tomography (PET/CT) and MRI. PET/CT provides important information on the local extent of disease as well as diffuse metastatic involvement. MRI offers soft tissue delineation and loco-regional disease involvement. The combination of these two technologies is key in diagnosis, treatment planning, and evaluating treatment response in gynecological malignancies. This review aims to assess the performance of PET/MRI in gynecologic cancer patients and outlines the technical challenges and clinical advantages of PET/MR systems when specifically applied to gynecologic malignancies.
3.
Jordal, Malin, 1973-, et al.
(author)
Surgical Healthcare Interventions after Female Genital Mutilation/Cutting : A Review of the Evidence
2022
In: CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY. - : IMR Press. - 0390-6663 .- 2709-0094. ; 49:6
Research review (peer-reviewed) abstract
Background: Female genital mutilation/cutting (FGM/C) is a global public health problem associated with an increased risk of physical, sexual, and mental health consequences. Surgical healthcare intervention may alleviate negative health consequences related to FGM/C. In this review, we aim to offer an overview of documented effects of surgical healthcare interventions after FGM/C, from the perspectives of both healthcare providers (HCPs) performing such interventions and the women receiving them.Methods: We searched four databases (PUBMED/MEDLINE, CINAHL, PsychInfo, Cochrane Library) for peer-reviewed articles published between 2000 and 2021, and retrieved a total of 1978 citations (1203 + 775). After scrutinizing the citations with the inclusion criteria (1) observable outcomes of surgical healthcare interventions after FGM/C, (2) HCPs' perceptions of FGM/C-related surgical healthcare and experiences of providing surgical care for FGM/C-affected women, and (3) FGM/C-affected women's perceptions and experiences of the effects of FGM/C-related surgical healthcare, we selected 38 articles to include in this review.Results: HCPs and FGM/C-affected women differed in their views on surgical interventions. While providers seemed to suggest premarital defibulation regardless of a woman's age and marital status, affected women voiced social and marital concerns related to defibulation, which sometimes overrode the physical consequences. On the other hand, some providers were reluctant to perform intrapartum defibulation due to uncertainty or misinformation about infibulated women's wishes, while women often expected and desired defibulation prenatally. And while gynecologists demonstrated skepticism towards clitoral reconstruction, most women who had undergone the procedure were satisfied, particularly regarding the psychosocial and sexual aspects.Conclusions: Providers and recipients of surgical interventions after FGM/C seem to display contrasting views on surgical intervention after FGM/C, which may have implications for healthcare recommendations as well as satisfaction. This apparent ambiguity between providers' and recipients' perceptions of surgical interventions needs further investigation.
4.
Escudero, Carlos, et al.
(author)
Brain Vascular Dysfunction in Mothers and Their Children Exposed to Preeclampsia
2023
In: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 80:2, s. 242-256
Research review (peer-reviewed) abstract
Preeclampsia is a maternal syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation associated with multisystemic complications, including brain alterations. Indeed, brain complications associated with preeclampsia are the leading direct causes of fetal and maternal morbidity and mortality, especially in low- and middle-income countries. In addition to the well-recognized long-term adverse cardiovascular effects of preeclampsia, women who have had preeclampsia have higher risk of stroke, dementia, intracerebral white matter lesions, epilepsy, and perhaps also cognitive decline postpartum. Furthermore, increasing evidence has also associated preeclampsia with similar cognitive and cerebral disorders in the offspring. However, the mechanistic links between these associations remain unresolved. This article summarizes the current knowledge about the cerebrovascular complications elicited by preeclampsia and the potential pathophysiological mechanisms involved, emphasizing the impaired brain vascular function in the mother and their offspring.
5.
Sundström Poromaa, Inger, et al.
(author)
Sex differences in depression during pregnancy and the postpartum period
2017
In: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 95:1-2, s. 719-730
Research review (peer-reviewed) abstract
Women have a lifetime risk of major depression double that of men but only during their reproductive years. This sex difference has been attributed partially to activational effects of female sex steroids and also to the burdens of pregnancy, childbirth, and parenting. Men, in contrast, have a reproductive period difficult to delineate, and research on the mental health of men has rarely considered the effects of fatherhood. However, the couple goes through a number of potentially stressing events during the reproductive period, and both mothers and fathers are at risk of developing peripartum depression. This Review discusses the literature on maternal and paternal depression and the endocrine changes that may predispose a person to depression at this stage of life, with specific focus on the hypothalamus-pituitary axis, oxytocin, and testosterone levels in men. Important findings on sex differences in the neural correlates of maternal and paternal behavior have emerged, highlighting the relevance of the emotional brain in mothers and the sociocognitive brain in fathers and pointing toward the presence of a common parents' brain. Additionally, sex differences in neurogenesis and brain plasticity are described in relation to peripartum depression.
6.
Eriksson, Ulf J., et al.
(author)
The status of diabetic embryopathy
2016
In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 121:2, s. 96-112
Research review (peer-reviewed) abstract
Diabetic embryopathy is a theoretical enigma and a clinical challenge. Both type 1 and type 2 diabetic pregnancy carry a significant risk for fetal maldevelopment, and the precise reasons for the diabetes induced teratogenicity are not clearly identified. The experimental work in this field has revealed a partial, however complex, answer to the teratological question, and we will review some of the latest suggestions.
7.
Hellberg, Dan
(author)
Sex Steroids and Cervical Cancer
2012
In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3045-3054
Research review (peer-reviewed) abstract
During the 19th century, studies indicated that reproductive events were involved in cervical cancer. Human papillomavirus (HPV) infection is a prerequisite for development of cancer, but co-factors, among them the action of sexual steroid hormones, are necessary. Childbirth has been an important risk factor but now probably plays a minor role in the industrialized world, where parity is low. Longterm oral contraceptive use has been thoroughly studied epidemiologically, and correlates to cervical cancer in most studies. In vitro studies on cervical cell lines transfected with HPV and animal studies indicate that sex steroid hormones are capable to induce cancer. In in vivo cervical cancer tissue studies there have been observations that endogenous progesterone in serum correlates to a negative pattern of expression of cellular and extracellular proteins, tumor markers. Immune response could be another mechanism. Estradiol might be associated with a positive pattern and high estradiol and low progesterone levels increase duration of survival in cervical cancer. Studies where treatment of compounds that influence sex steroid hormones have been given are rare and have been disappointing.
8.
Abeid, Muzdalifat, 1973-, et al.
(author)
Evaluation of a training program for health care workers to improve the quality of care for rape survivors : a quasi-experimental design study in Morogoro, Tanzania
2016
In: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 9
Research review (peer-reviewed) abstract
BACKGROUND:Sexual violence against women and children in Tanzania and globally is a human rights violation and a developmental challenge.OBJECTIVE:The aim of this study was to assess the impact of training health professionals on rape management. The specific objectives were to evaluate the changes of knowledge and attitudes toward sexual violence among a selected population of health professionals at primary health care level.DESIGN:A quasi-experimental design using cross-sectional surveys was conducted to evaluate health care workers' knowledge, attitude, and clinical practice toward sexual violence before and after the training program. The study involved the Kilombero (intervention) and Ulanga (comparison) districts in Morogoro region. A total of 151 health professionals at baseline (2012) and 169 in the final assessment (2014) participated in the survey. Data were collected using the same structured questionnaire. The amount of change in key indicators from baseline to final assessment in the two areas was compared using composite scores in the pre- and post-interventions, and the net intervention effect was calculated by the difference in difference method.RESULTS:Overall, there was improved knowledge in the intervention district from 55% at baseline to 86% and a decreased knowledge from 58.5 to 36.2% in the comparison area with a net effect of 53.7% and a p-value less than 0.0001. The proportion of participants who exhibited an accepting attitude toward violence declined from 15.3 to 11.2% in the intervention area but increased from 13.2 to 20.0% in the comparison area.CONCLUSIONS:Training on the management of sexual violence is feasible and the results indicate improvement in healthcare workers' knowledge and practice but not attitudes. Lessons learned from this study for successful replication of such an intervention in similar settings require commitment from those at strategic level within the health service to ensure that adequate resources are made available.
9.
Altmäe, Signe, et al.
(author)
Guidelines for the design, analysis and interpretation of 'omics' data : focus on human endometrium
2013
In: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 20:1, s. 12-28
Research review (peer-reviewed) abstract
BACKGROUND 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.METHODS Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.RESULTS The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.CONCLUSION A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.
10.
Aravidis, Christos, et al.
(author)
A familial case of Muenke syndrome. Diverse expressivity of the FGFR3 Pro252Arg mutation - case report and review of the literature
2014
In: The Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 27:14, s. 1502-1506
Research review (peer-reviewed) abstract
Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated syndrome, which was first described in late 1990s. Muenke syndrome is an autosomal dominant disorder characterized mainly by coronal suture craniosynostosis, hearing impairment and intellectual disability. The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p. Pro250Arg of the protein product. Despite the fact that the mutation rate at this nucleotide is one of the most frequently described in human genome, few Muenke familial case reports are published in current literature. We describe individuals among three generations of a Greek family who are carriers of the same mutation. Medical record and physical examination of family members present a wide spectrum of clinical manifestations. In particular, a 38-year-old woman and her father appear milder clinical findings regarding craniofacial characteristics compared to her uncle and newborn female child. This familial case illustrates the variable expressivity of Muenke syndrome in association with an identical gene mutation.
