Search

Human pregnancy is frequently accompanied by nausea and vomiting that may become severe and life-threatening, as in hyperemesis gravidarum (HG), the cause of which is unknown. Growth Differentiation Factor-15 (GDF15), a hormone known to act on the hindbrain to cause emesis, is highly expressed in the placenta and its levels in maternal blood rise rapidly in pregnancy. Variants in the maternal GDF15 gene are associated with HG. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We found that the great majority of GDF15 in maternal circulation is derived from the feto-placental unit and that higher GDF15 levels in maternal blood are associated with vomiting and are further elevated in patients with HG. Conversely, we found that lower levels of GDF15 in the non-pregnant state predispose women to HG. A rare C211G variant in GDF15 which strongly predisposes mothers to HG, particularly when the fetus is wild-type, was found to markedly impair cellular secretion of GDF15 and associate with low circulating levels of GDF15 in the non-pregnant state. Consistent with this, two common GDF15 haplotypes which predispose to HG were associated with lower circulating levels outside pregnancy. The administration of a long-acting form of GDF15 to wild-type mice markedly reduced subsequent responses to an acute dose, establishing that desensitisation is a feature of this system. GDF15 levels are known to be highly and chronically elevated in patients with beta thalassemia. In women with this disorder, reports of symptoms of nausea or vomiting in pregnancy were strikingly diminished. Our findings support a causal role for fetal derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to GDF15, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Introduction: Morel–Lavallée (MLL) is an uncommon entity that is missed by many physicians, it is the result of a shearing force that leads to degloving of the subcutaneous fat from the underlying deep fascia. Case Report: We present a case of a 15-year-old male patient who presented 3 months after the initial crush injury with a large MLL lesion at the lateral aspect of the right proximal thigh. He was treated with incision and drainage with compressive dressing and a negative pressure drain. Conclusion: Diagnosis of MLL is usually clinical and can be aided with radiological tools like MRI that is the gold standard of imaging in this lesion. Several treatment options are available, ranging from conservative treatment with compressive bandages to percutaneous drainage, injection of sclerotic agents, and surgical treatment with incision, drainage, and debridement. Diagnosis and treatment should be familiar to all caregivers to prevent further complications that could be life or organ-threatening. Keywords: Morel–Lavallée, thigh trauma, chronic Morel–Lavallée, thigh mass.

Virtual reality environments offer great opportunities to study the performance of brain-computer interfaces (BCIs) in real-world contexts. As real-world stimuli are typically multimodal, their neuronal integration elicits complex response patterns. To investigate the effect of additional auditory cues on the processing of visual information, we used virtual reality to mimic safety-related events in an industrial environment while we concomitantly recorded electroencephalography (EEG) signals. We simulated a box traveling on a conveyor belt system where two types of stimuli – an exploding and a burning box – interrupt regular operation. The recordings from 16 subjects were divided into two subsets, a visual-only and an audio-visual experiment. In the visual-only experiment, the response patterns for both stimuli elicited a similar pattern – a visual evoked potential (VEP) followed by an event-related potential (ERP) over the occipital-parietal lobe. Moreover, we found the perceived severity of the event to be reflected in the signal amplitude. Interestingly, the additional auditory cues had a twofold effect on the previous findings: The P1 component was significantly suppressed in the case of the exploding box stimulus, whereas the N2c showed an enhancement for the burning box stimulus. This result highlights the impact of multisensory integration on the performance of realistic BCI applications. Indeed, we observed alterations in the offline classification accuracy for a detection task based on a mixed feature extraction (variance, power spectral density, and discrete wavelet transform) and a support vector machine classifier. In the case of the explosion, the accuracy slightly decreased by –1.64% p. in an audio-visual experiment compared to the visual-only. Contrarily, the classification accuracy for the burning box increased by 5.58% p. when additional auditory cues were present. Hence, we conclude, that especially in challenging detection tasks, it is favorable to consider the potential of multisensory integration when BCIs are supposed to operate under (multimodal) real-world conditions.

Synthetic platforms for mimicking artificial organelles or for designing multivalent protein therapeutics for targeting cell surface, extracellular matrix, and tissues are in the focus of this study. Furthermore, the availability of a multi-functionalized and stimuli-responsive carrier system is required that can be used for sequential in situ and/or post loading of different proteins combined with post-functionalization steps. Until now, polymersomes exhibit excellent key characteristics to fulfill those requirements, which allow specific transport of proteins and the integration of proteins in different locations of polymeric vesicles. Herein, different approaches to fabricate multivalent protein-loaded, pH-responsive, and pH-stable polymersomes are shown, where a combination of therapeutic action and targeting can be achieved, by first choosing two model proteins such as human serum albumin and avidin. Validation of the molecular parameters of the multivalent biohybrids is performed by dynamic light scattering, cryo-TEM, fluorescence spectroscopy, and asymmetrical flow-field flow fractionation combined with light scattering techniques. To demonstrate targeting functions of protein-loaded polymersomes, avidin post-functionalized polymersomes are used for the molecular recognition of biotinylated cell surface receptors. These versatile protein-loaded polymersomes present new opportunities for designing sophisticated biomolecular nanoobjects in the field of (extracellular matrix) protein therapeutics.

BACKGROUND This study aimed to risk-stratify chest pain as a presenting symptom in patients with a diagnosis of pulmonary thromboembolism (PE) to assess for any association. In addition, this study aimed to assess traditionally acknowledged PE risk factors in an Australian population. METHODS This was a retrospective single-centre cohort study assessing patients who presented to our emergency department during the period of 1 January 2019 to 1 January 2020. 730 consecutive patients who went on to computed tomography pulmonary angiography (CTPA) examination after presentation were included. RESULTS The rate of CTPA being positive in this study was 11.6% (85/730). Chest pain was associated with a non-significant reduction in the odds of PE (OR 0.774, P = 0.327). Univariate analysis showed significantly increased odds of a diagnosis of PE with presentation for leg pain/swelling (OR 6.670, P

Catheter-directed thrombolysis (CDT) is increasingly performed for acute pulmonary embolism (PE) because it is presumed to provide similar therapeutic benefits to systemic thrombolysis, while decreasing the dose of thrombolytic required and the associated risks. Contemporary suction thrombectomy (ST) devices have entered the market as minimal or no-lytic alternatives, but there is no evidence on their comparative effectiveness. This study aims to compare clinical outcomes of these two interventional alternatives.Consecutive patients who underwent a ST catheter intervention for massive or submassive PE between 2011 and 2017 were identified. For each of these patients, a nearest-neighbor matching was implemented to identify at least three CDT patients who matched as closely as possible on the following six variables: PE type, age, gender, acute deep venous thrombosis, pulmonary disease, and year of procedure. The end point was clinical success defined as meeting all the following criteria: survival to hospital discharge without major bleeding (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries moderate or severe), perioperative stroke or other major adverse procedure-related event, and decompensation for submassive or persistent shock for massive PE.Of 277 patients who received an intervention for acute PE, 54 CDT (63.5 ± 14.2 years of age; 18 massive PE) were matched with 18 ST (64.1 ± 14.1 years of age; 6 massive PE) patients. In the CDT group, 38 (70.4%) received ultrasound-assisted thrombolysis. The ST group had significantly more patients who had a major contraindication for lytics (1 [1.9%] for CDT vs 9 [50%] for ST; P .001). There was no difference in major bleeding (8 [14.8%] for CDT vs 3 [16.7%] for ST; P.999; Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries severe 1 [1.8%] for CDT vs 1 [5.6%] for ST; P.999), stroke (3.7% for CDT vs 0 for ST; P = .408), or death (3.7% for CDT vs 16.7% for ST; P = .096). One patient in the ST group suffered tricuspid valve rupture and two patients in CDT group required surgical thrombectomy. Clinical success was not statistically different between groups (75.9% for CDT vs 61.1% for ST; P = .224). The association was similar when assessing the right/left ventricular ratio improvement (0.30 ± 0.19 for CDT vs 0.17 ± 0.16 for ST; P = .097), or the subgroup of patients with submassive PE (86.1% for CDT vs 66.7% for ST; P = .135).CDT seems to have similar outcomes with ST in the management of acute PE, although larger, more homogenous data are needed. In our experience, ST should be viewed as a complementary alternative for patients with contraindication for thrombolytics or severely compromised hemodynamic profile and can yield good outcomes in an otherwise highly morbid population.

Insufficiency fractures are a common complication of bisphosphonate use and have recently been reported in association with Roux-en-Y Gastric Bypass Surgery (RYGB). This study reports a case of a 62-year-old female, 6 years status post Mini Gastric Bypass – One Anastomosis Gastric Bypass (MGB-OAGB), presenting to our institution with bilateral groin pain of 8 months duration unresponsive to conservative management. Diagnostic workup revealed bilateral medial sub-trochanteric insufficiency fractures. She underwent bilateral intramedullary fixation with satisfactory results. This case might suggest a particular fracture pattern in patients undergoing MGB-OAGB, and raises awareness to screen patients with such presentation to rule out a fracture or to prevent the extension of an existing one.

Arginine is a semi-essential amino acid which serves as a substrate for nitric oxide (NO) production by nitric oxide synthase (NOS) and a precursor for various metabolites including ornithine, creatine, polyamines, and agmatine. Arginase competes with nitric oxide synthase for substrate arginine to produce orthinine and urea. There is contradictory evidence in the literature on the role of nitric oxide in the pathophysiology of traumatic brain injury (TBI). These contradictory perspectives are likely due to different NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) which are expressed in the central nervous system. Of these, the role of nNOS in acute injury remains less clear. This study aimed to employ a genetic approach by overexpressing arginase isoforms specifically in neurons using a Thy-1 promoter to manipulate cell autonomous NO production in the context of TBI. The hypothesis was that increased arginase would divert arginine from pathological NO production. We generated 2 mouse lines that overexpress arginase I (a cytoplasmic enzyme) or arginase II (a mitochondrial enzyme) in neurons of FVB mice. We found that two-weeks after induction of controlled cortical injury, overexpressing arginase I but not arginase II in neurons significantly reduced contusion size and contusion index compared to wild-type (WT) mice. This study establishes enhanced neuronal arginase levels as a strategy to affect the course of TBI and provides support for the potential role of neuronal NO production in this condition.