Mapping the lack of public initiative against female genital mutilation in Denmark.

BACKGROUND: Female genital mutilation (FGM) is a harmful practice prevalent in 35 countries, mainly in Africa, as well as in some Middle Eastern countries and a few Asian countries. FGM comprises all procedures that involve partial or complete resection of, or other injury to, external female genitalia for non-medical reasons. The practice of FGM has spread to Western countries due to migration. The European Institute for Gender Equality recommend that FGM be combatted by nationally coordinated efforts through implementation of national action plans, guidelines for professionals as well as comprehensive research in the field. FGM was outlawed in Denmark 2003, but no national actions plan has been implemented. Instead, the task of combatting FGM is currently under the responsibility of local governments in the form of the 98 municipalities. The aim of this study is to investigate the Danish municipalities' efforts to prevent FGM on the local level, and whether these initiatives are in accordance with international recommendations and standards. METHODS: All 98 Danish municipalities were invited to respond to a questionnaire regarding FGM in their respective municipalities. The inclusion process and questionnaire was designed after a pilot study, which included 29 municipalities. The questionnaire consisted of four overall areas of focus: "action plan", "registration", "information material" and "preventive initiatives". Demographic data were gathered from the 2017 census by Statistics Denmark. Risk countries were defined as countries with a tradition for FGM, identified from the 2016 UNICEF definition. RESULTS: A total of 67 municipalities participated in the study. At the time of census, 1.8% of the Danish population was immigrants with origins in risk countries. A total of 10.4% of the responding municipalities indicated to have implemented a specific action plan against FGM. A total of 7,5% had implemented specific preventive initiatives against FGM. Registration of reported FGM cases were indicated to be performed in 73.1% of the responding municipalities; however, only 17.9% stated to perform registration of FGM specifically as such, and not as general child abuse. CONCLUSIONS: Our study shows that the current situation of FGM registration and prevention being under local administrative responsibility in the 98 Danish municipalities has led to a severe lack of coordinated public initiative against FGM.

Hypoxia inducible factor 1-alpha in the pathogenesis of abdominal aortic aneurysms in vivo: A narrative review.

Abdominal aortic aneurysms (AAAs) are relatively common, primarily among older men, and, in the case of rupture, are associated with high mortality. Although procedure-related morbidity and mortality have improved with the advent of endovascular repair, noninvasive treatment and improved assessment of AAA rupture risk should still be sought. Several cellular pathways seem contributory to the histopathologic changes that drive AAA growth and rupture. Hypoxia inducible factor 1-alpha (HIF-1α) is an oxygen-sensitive protein that accumulates in the cytoplasm under hypoxic conditions and regulates a wide array of downstream effectors to hypoxia. Examining the potential role of HIF-1α in the pathogenesis of AAAs is alluring, because local hypoxia is known to be present in the AAA vessel wall. A systematic scoping review was performed to review the current evidence regarding the role of HIF-1α in AAA disease in vivo. After screening, 17 studies were included in the analysis. Experimental animal studies and human studies show increased HIF-1α activity in AAA tissue compared with healthy aorta and a correlation of HIF-1α activity with key histopathologic features of AAA disease. In vivo HIF-1α inhibition in animals protects against AAA development and growth. One study reveals a positive correlation between HIF-1α-activating genetic polymorphisms and the risk of AAA disease in humans. The main findings suggest a causal role of HIF-1α in the pathogenesis of AAAs in vivo. Further research into the HIF-1α pathway in AAA disease might reveal clinically applicable pharmacologic targets or biomarkers relevant in the treatment and monitoring of AAA disease.

Open thrombectomy and retrograde mesenteric stenting as a treatment for acute in chronic occlusive mesenteric ischemia: A case report.

In this case report, we outline a tailored approach for a complex patient with acute in chronic proximal occlusive mesenteric disease complicated with fresh thrombosis and a heavily calcified aorta, where the standard treatment proved suboptimal. We outline the surgical considerations that ultimately led to performing a hybrid procedure of open thrombectomy combined with retrograde open mesenteric stenting of the superior mesenteric artery. The patient was a 75-year-old male, with a history of severe arteriosclerosis presenting with abdominal pain over 48 h. An initial diagnostic laparoscopy was performed at a local hospital showing signs of mesenteric ischemia. The patient was transferred to a major trauma hospital, where the patient underwent an open thrombectomy combined with retrograde open mesenteric stenting. The patient's intestines showed no signs of necrosis after surgery, and the patient was discharged nine days after surgery. The patient has experienced no complications and was alive at the 90-day follow-up. This case report outlines the clinical information available to the surgeons, leading to their decision of an infrequently used approach in emergency surgery. We believe that hybrid procedures utilizing the strengths of both open and endovascular surgery should be considered in complex patients where standard treatment options are suboptimal. European guidelines state that retrograde open mesenteric stenting should be performed when antegrade stenting fails, utilizing a through-and-through procedure. We believe that in some cases it is beneficial to the patient to use a hybrid approach including retrograde open mesenteric stenting as first line treatment.

Behavioral variant of frontotemporal dementia mimicking Huntington's disease.

Behavioral changes and cognitive decline are the core clinical manifestations in the behavioral variant of frontotemporal dementia (bv-FTD). The behavioral changes may include characteristic stereotypic movements. These movements, although without clear purpose, are not involuntary. Involuntary movements are usually not seen in FTD.Two patients with involuntary choreoathetoid movements but otherwise presenting a bv-FTD-phenotype were referred and Huntington's disease (HD) was suspected. The diagnoses of bv-FTD were made after comprehensive assessment and exclusion of other diagnoses, including HD and Huntington's disease-like (HDL) phenotypes. Although a definite diagnosis will require neuropathological confirmation, we conclude that a HDL phenotype may be part of the clinical spectrum of the bv-FTD phenotype.

Assessment of Dementia in Individuals with Dual Sensory Loss: Application of a Tactile Test Battery.

BACKGROUND/AIMS: Individuals with dual sensory loss (DSL) are more likely to experience cognitive decline with age than individuals without sensory loss. Other studies have pointed to the challenges in assessing cognitive abilities in individuals with DSL, as most existing instruments rely on use of vision and hearing. The aim of this study was to develop and evaluate a Tactile Test Battery (TTB) for cognitive assessment in individuals with DSL. METHOD: Twenty elderly individuals with DSL, 20 with diagnosed dementia, and 20 without dementia or DSL (controls) completed the following tactile tests developed for the present study: Spatial learning, Spatial recall, Tactile form board, Clock reading, and Naming. The participants with dementia and controls also completed the Mini-Mental State Examination (MMSE). RESULTS: Overall, participants with dementia performed significantly worse on the tactile tests than participants with DSL and control participants. No significant differences on the tactile tests were found between participants with DSL and controls. The TTB and MMSE scores correlated significantly. CONCLUSION: The findings from this study of applying tactile tests for cognitive examination in individuals with DSL are promising. They indicate that symptoms of dementia can be differentiated from symptoms related to DSL.

Tubastatin A prevents hemorrhage-induced endothelial barrier dysfunction.

BACKGROUND: Microvascular hyperpermeability resulting from endothelial barrier dysfunction (EBD) is associated with worse clinical outcomes in trauma-induced hemorrhagic shock. We have previously shown that treatment with Tubastatin A (TubA), a histone deacetylase 6 inhibitor, improves outcomes in animal models of shock. In this study, we investigate whether TubA treatment may prevent trauma-related EBD. METHODS: Wistar-Kyoto rats subjected to 40% hemorrhage were treated with TubA or vehicle control. Acute lung injury (ALI) was assessed histologically from tissues harvested 6 hours posthemorrhage. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured in EGM BulletKit medium. Medium was exchanged for glucose-free Dulbecco's Modified Eagle Medium (0.5% fetal bovine serum) with or without TubA, and cells were placed in an anoxic chamber (5% CO2, 95% N2, 20-48 hours). Expression of acetylated tubulin and hypoxia-inducible factor 1α was measured by Western blot. Soluble Intercellular Adhesion Molecule-1 concentration within the medium, a marker of endothelial integrity, was determined using enzyme-linked immunosorbent assay. Monolayers were assessed for permeability via transwell assays using fluorescein isothiocyanate-labeled albumin. RESULTS: Rats treated with TubA had significantly reduced ALI relative to vehicle control. In vitro, TubA significantly attenuated anoxia-induced hyperpermeability, hypoxia-inducible factor 1α expression, and glycocalyx shedding. CONCLUSIONS: Our findings demonstrate that TubA prevents hemorrhage-induced ALI in rats. Additionally, we have shown that TubA prevents anoxia-induced EBD in vitro. Taken together, these results suggest that TubA could attenuate microvascular hyperpermeability related to hemorrhagic shock.

Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma.

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mm Hg) for 2 h, and then randomized to resuscitation with normal saline (NS), FFP, or LP (n = 5 swine/group). Animals were recovered and monitored for 30 d, during which time neurological recovery was assessed. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on post-injury days (PID) three and 10. Animals were euthanized on PID 30. The severity of shock and response to resuscitation was similar in all groups. When compared with NS-treated animals, plasma-treated animals (FFP and LP) had significantly lower neurologic severity scores (PID 1-7) and a faster return to baseline neurological function. There was no significant difference in brain lesion sizes between groups. LP treatment was well tolerated and similar to FFP. In this clinically relevant large animal model of severe TBI, HS, and polytrauma, we have shown that plasma-based resuscitation strategies are safe and result in neurocognitive recovery that is faster than recovery after NS-based resuscitation.

Posttraumatic levels of liver enzymes can reduce the need for CT in children: a retrospective cohort study.

BACKGROUND: Computed tomography (CT) is the gold standard in the initial evaluation of the hemodynamically stable patient with suspected liver trauma. However, the adverse effects of radiation exposure are of specific concern in the pediatric population. It is therefore desirable to explore alternative diagnostic modalities. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are hepatic enzymes, which are elevated in peripheral blood in relation to liver injury. The aim of the present study was to investigate a potential role of normal liver transaminase levels in the decision algorithm in suspected pediatric blunt liver trauma. METHODS: Retrospective analysis of consecutively collected data from children (0-17 years) with blunt liver trauma, admitted to a single trauma centre in Denmark, between 2000 and 2013. Patients underwent abdominal CT during initial evaluation, and initial AST and/or ALT was measured. Based on local guidelines, we set the threshold for blood AST and ALT level to 50 IU/L. Nonparametric statistical tests were used. RESULTS: Sixty consecutive children with liver injury following blunt abdominal trauma were enrolled in the study. All patients with normal AST and/or ALT level were treated conservatively with success. Information on both AST and ALT was available in 47 children. Of these 47 children, three children had AST and ALT levels ≤50 IU/L. These children suffered from grade I liver injuries, and were treated conservatively with no complications. DISCUSSION: All children who presented with blunt liver injury and AST and ALT levels ≤50 IU/L did not require treatment. These findings indicate that AST and ALT could be included in an updated management algorithm as a screening method to avoid abdominal CT. Notable limitations to the study was the retrospective method of data collection, without inclusion of a control group. CONCLUSIONS: CT seems superfluous in the initial evaluation of hemodynamically stable children with suspected blunt liver injury and blood AST and ALT levels ≤50 IU/L.

Early resuscitation with lyophilized plasma provides equal neuroprotection compared with fresh frozen plasma in a large animal survival model of traumatic brain injury and hemorrhagic shock.

BACKGROUND: Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) is highly lethal. In previous models of combined TBI + HS, we showed that early resuscitation with fresh frozen plasma (FFP) improves neurologic outcomes. Delivering FFP, however, in austere environments is difficult. Lyophilized plasma (LP) is a logistically superior alternative to FFP, but data are limited regarding its efficacy for treatment of TBI. We conducted this study to determine the safety and long-term outcomes of early treatment with LP in a large animal model of TBI + HS. METHODS: Adult anesthetized swine underwent TBI and volume-controlled hemorrhage (40% blood volume) concurrently. After 2 hours of shock, animals were randomized (n = 5 per /group) to FFP or LP (1× shed blood) treatment. Serial blood gases were drawn, and thromboelastography was performed on citrated, kaolin-activated whole-blood samples. Five hours after treatment, packed red blood cells were administered, and animals recovered. A 32-point Neurologic Severity Score was assessed daily for 30 days (0 = normal, 32 = most severe injury). Cognitive functions were tested by training animals to retrieve food from color-coded boxes. Brain lesion size was measured on serial magnetic resonance imaging, and an autopsy was performed at 30 days. RESULTS: The severity of shock and the degree of resuscitation were similar in both groups. Administration of FFP and LP was well tolerated with no differences in reversal of shock or thromboelastography parameters. Animals in both groups displayed the worst Neurologic Severity Score on postoperative Day 1 with rapid recovery and return to baseline within 7 days of injury. Lesion size on Day 3 in FFP-treated animals was 645 ± 85 versus 219 ± 20 mm in LP-treated animals (p < 0.05). There were no differences in cognitive functions or delayed treatment-related complications. CONCLUSIONS: Early treatment with LP in TBI + HS is safe and provides neuroprotection that is comparable to FFP.

Histone deactylase gene expression profiles are associated with outcomes in blunt trauma patients.

BACKGROUND: Treatment with histone deacetylase (HDAC) inhibitors, such as valproic acid, increases survival in animal models of trauma and sepsis. Valproic acid is a pan-inhibitor that blocks most of the known HDAC isoforms. Targeting individual HDAC isoforms may increase survival and reduce complications, but little is known of the natural history of HDAC gene expression following trauma. We hypothesized that distinct HDAC isoform gene expression patterns would be associated with differences in outcomes following trauma. METHODS: Twenty-eight-day longitudinal HDAC leukocyte gene expression profiles in 172 blunt trauma patients were extracted from the Inflammation and the Host Response to Injury (Glue Grant) data set. Outcome was classified as complicated (death or no recovery by Day 28, n = 51) or uncomplicated (n = 121). Mixed modeling was used to compare the HDAC expression trajectories between the groups, corrected for Injury Severity Score (ISS), base deficit, and volume of blood products transfused during the initial 12 hours following admission. Weighted gene correlation network analysis identified modules of genes with significant coexpression, and HDAC genes were mapped to these modules. Biologic function of these modules was investigated using the Gene Ontology database. RESULTS: Elevated longitudinal HDAC expression trajectories for HDAC1, HDAC3, HDAC6, and HDAC11 were associated with complicated outcomes. In contrast, suppressed expression of Sirtuin 3 (SIRT3) was associated with adverse outcome (p < 0.01). Weighted gene correlation network analysis identified significant coexpression of HDAC and SIRT genes with genes involved in ribosomal function and down-regulation of protein translation in response to stress (HDAC1), T-cell signaling, and T-cell selection (HDAC3) as well as coagulation and hemostasis (SIRT3). No coexpression of HDAC11 was identified. CONCLUSION: Expression trajectories of HDAC1, HDAC3, HDAC6, HDAC11, and SIRT3 correlate with outcomes following trauma and may potentially serve as biomarkers. They may also be promising targets for pharmacologic intervention. The effects of HDAC and SIRT gene expression in trauma may be mediated through pathways involved in ribosomal and T-cell function as well as coagulation and hemostasis. LEVEL OF EVIDENCE: Prognostic study, level III.

Heart rate variability and intima media thickness.

Increased activity in the sympathetic nervous system is part of the physiological stress response and is expressed in the heart rate variability (HRV). The objective of this study was to examine associations of HRV and intima media thickness (IMT). In 2002, satisfactory measurements of HRV of 78 voluntary participants were made, both during a stress test and during sleep. IMT in 2002 and the progression in IMT from 1998 to 2002 were analyzed in relation to measures of HRV. HRV was negatively associated with IMT and IMT progression both during test and sleep. In men with higher IMT measures than mean the low frequency-high frequency ratio was higher during sleep than during test, perhaps mirroring a lack of ability to recovery. HRV was negatively associated with IMT and IMT progression. HRV may be part of the pathophysiological pathway between psychological strain and atherosclerosis.

Genetic programming over context-free languages with linear constraints for the knapsack problem: first results.

In this paper, we introduce genetic programming over context-free languages with linear constraints for combinatorial optimization, apply this method to several variants of the multidimensional knapsack problem, and discuss its performance relative to Michalewicz's genetic algorithm with penalty functions. With respect to Michalewicz's approach, we demonstrate that genetic programming over context-free languages with linear constraints improves convergence. A final result is that genetic programming over context-free languages with linear constraints is ideally suited to modeling complementarities between items in a knapsack problem: The more complementarities in the problem, the stronger the performance in comparison to its competitors.