Advanced diffusion MRI provides evidence for altered axonal microstructure and gradual peritumoral infiltration in GBM in comparison to brain metastases.

PURPOSE: In contrast to peritumoral edema in metastases, GBM is histopathologically characterized by infiltrating tumor cells within the T2 signal alterations. We hypothesized that depending on the distance from the outline of the contrast-enhancing tumor we might reveal imaging evidence of gradual peritumoral infiltration in GBM and predominantly vasogenic edema around metastases. We thus investigated the gradual change of advanced diffusion metrics with the peritumoral zone in metastases and GBM. METHODS: In 30 patients with GBM and 28 with brain metastases, peritumoral T2 hyperintensity was segmented in 33% partitions based on the total volume beginning at the enhancing tumor margin and divided into inner, middle and outer zones. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy and mean diffusivity as well as Diffusion Microstructure Imaging (DMI)-based parameters Dax-intra, Dax-extra, V­CSF and V-intra were employed to assess group-wise differences between inner and outer zones as well as within-group gradients between the inner and outer zones. RESULTS: In metastases, fractional anisotropy and Dax-extra were significantly reduced in the inner zone compared to the outer zone (FA p = 0.01; Dax-extra p = 0.03). In GBM, we noted a reduced Dax-extra and significantly lower intraaxonal volume fraction (Dax-extra p = 0.008, V­intra p = 0.006) accompanied by elevated axial intraaxonal diffusivity in the inner zone (p = 0.035). Between-group comparison of the outer to the inner zones revealed significantly higher gradients in metastases over GBM for FA (p = 0.04) as well as the axial diffusivity in the intra- (p = 0.02) and extraaxonal compartment (p < 0.001). CONCLUSION: Our findings provide evidence of gradual alterations within the peritumoral zone of brain tumors. These are compatible with predominant (vasogenic) edema formation in metastases, whereas our findings in GBM are in line with an axonal destructive component in the immediate peritumoral area and evidence of tumor cell infiltration with accentuation in the tumor's vicinity.

Raising patient voices in medical education: an assessment of patient perceived effect of social determinants of health conversations and the patient-physician relationship on quality of obstetric care, to inform the development of patient driven medical education curricula.

Background: Conventional medical education lacks the lived experiences of patients which may authentically convey the social determinants of health (SDOH) and resulting health disparities. Videos of first-person patient narratives may prove a valuable education tool in this regard. The objective of this study is to investigate how patient demographics, satisfaction with care, and patient-physician relationships influence obstetric patient interest and willingness to contribute to a SDOH video curriculum by sharing their lived experiences through first-person narratives. Methods: Study design included an anonymous, cross-sectional survey and an optional semi-structured telephone interview. Participants were 18 years old with a live-birth delivery <8 weeks prior to recruitment and received care during their pregnancy at Los Angeles General Medical Center (LAGMC). Variables surveyed included demographics, satisfaction with care, aspects of the patient-physician relationship, perceived utility, and personal interest in contributing to an educational SDOH video. A bivariate analysis was conducted to compare participants' characteristics and responses on interest in contributing and perceived helpfulness of first-person patient SDOH videos. Results: 72.43% of participants (N = 70) believed a patient's first-person video on SDOH would be "Helpful" in preparing physicians to provide competent medical care; however, 71.43% responded "No" to "Interest" in sharing with physicians their experiences with SDOH. English preference and being U.S. born were factors significantly associated with viewing first-person SDOH video as "Helpful" (P > 0.001). Major themes from telephone interviews reflected enthusiasm for first-person patient narratives and perceived benefits of using patient experiences to educate physicians on SDOH. However, participants cited barriers to disclosing SDOH including brief and strictly clinical interactions with physicians, lack of continuity of care, and fear of being judged by physicians. Conclusion: While most participants recognized the utility of addressing social needs in medical education and reported satisfaction with their obstetricians and care, these factors did not uniformly translate into willingness to contribute first-person patient narratives. To improve the representation of patients from racial, ethnic, gender, linguistic, and sexual minorities into medical curricula, further research and strategies are needed to overcome the barriers discouraging patient disclosure of social needs to physicians.

Protein signatures of spontaneous lipolysis and lipoprotein lipase activity in cow's milk.

Spontaneous milk lipolysis refers to the breakdown of triacylglycerols in milk. Lipolysis impacts the organoleptic value of milk by causing off-flavours and reduces the technological properties of milk. Lipolysis is caused by lipoprotein lipase (LPL), a tightly regulated enzyme in milk. Our objective was to identify robust biomarkers of lipolysis and putative regulators of LPL enzyme in bovine milk. To achieve this goal, we used feed restriction as a lever to generate highly contrasted samples with regard to milk lipolysis. We combined statistical methods on proteomics data, milk lipolysis and LPL activity values. Following this strategy, we identified CD5L and GP2 as robust biomarkers of high lipolysis in cow milk. We also identified HID1, SURF4 and CUL9 as putative inhibitors of the lipolytic process in the milk. We thus proposed 5 putative biomarkers to be considered in future tools to manage milk lipolysis. SIGNIFICANCE: This manuscript is notable in three aspects. First, this is the first evaluation of the milk proteome relative to milk lipolysis or LPL activity. Second, the relationship between the abundance of proteins and milk traits was evaluated by a combination of univariate and multivariate analyses. Third, we provide a short list of five proteins to be tested in a larger population to feed the pipeline of biomarker discovery.

Consistent Value of Two-Stage Pedicle Flaps in the Age of Microsurgical Maxillofacial Reconstruction.

Introduction: Up to the second half of the twentieth century, pedicled flaps marked the gold standard in reconstructive surgery. Followed by the introduction of microsurgical techniques, these flaps were increasingly abandoned. We conducted a retrospective study to determine the value of two-stage pedicle flaps in modern maxillofacial reconstruction. Material & Methods: A chart review from October 2017 to November 2020 was performed to identify patients who were treated by a two-stage pedicle flap in our Department of Oral and Maxillofacial Surgery. Results: A total of 31 patients, 17 female and 14 males received 36 two-stage pedicle flaps. All patients were in noticeably impaired health condition with a majority of ASA-score 3. The defect location mainly contained extraoral resections (58.3%). A variety of flaps were harvested consisting of buccal flaps, Abbe flaps, forehead flaps, deltopectoral flaps, nasolabial flaps, and a tubed flap. Discussion: The study outlines two indications for the use of two-stage pedicle flaps. Firstly, as a back-up strategy in heavily pre-treated wound beds and secondly in an almost contrarily indication as a first-choice reconstructive option of the facial skin in esthetic demanding cases. Conclusion: The timesaving and straight forward surgical approach as well as their low postsurgical complications and strong long-time success rates secure the two-stage pedicle flap a justified niche role in times of microsurgical maxillofacial reconstruction. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-021-01635-9.

Clinical feasibility of diffusion microstructure imaging (DMI) in acute ischemic stroke.

BACKGROUND: Diffusion microstructure imaging (DMI) is a fast approach to higher-order diffusion-weighted magnetic resonance imaging that allows robust decomposition and characterization of diffusion properties of brain tissue into intra-axonal, extra-axonal, and a free water-compartment. We now report the application of this technique to acute ischemic stroke and demonstrate its potential applicability to the daily clinical routine. METHODS: Thirty-eight patients diagnosed with acute ischemic stroke were scanned using an accelerated multi-shell diffusion-weighted imaging protocol (median delay between onset and MRI scan of 113 min). DMI metrics were calculated and the apparent diffusion coefficient (ADC) derived from conventional diffusion-weighted imaging was used for comparison. The resulting DMI parameter maps were analysed for their potential to improve infarct core delineation, and a receiver-operating characteristic (ROC) analysis was subsequently performed for automated infarct segmentation. RESULTS: Robust parameter maps for diffusion microstructure properties were obtained in all cases. Within the ischemic tissue, an increase in the volume fraction of the intra-axonal compartment was accompanied by a volume fraction reduction in the other two compartments. Moreover, diffusivity was reduced in all three compartments, with intra-axonal diffusivity showing the highest degree of contrast. The intra-axonal diffusion coefficient maps were subsequently found to perform better than single-shell ADC-derived segmentation in terms of automatic segmentation of the infarct core (area under the curve = 0.98 vs 0.92). CONCLUSIONS: The alterations to the ischemic core detected by DMI are in line with the "beading-model" of non-uniform neurite swelling under ischemic conditions. When compared to conventional single-shell diffusion-weighted imaging, DMI metrics are associated with improved discriminative power for delineating and characterizing ischemic changes. This might allow a more detailed assessment of infarct age, severity of damage, the degree of reversibility, and outcome.

Gray-White Matter Blurring of the Temporal Pole Associated With Hippocampal Sclerosis: A Microstructural Study Involving 3 T MRI and Ultrastructural Histopathology.

Hippocampal sclerosis (HS) is often associated with gray-white matter blurring (GMB) of the anterior temporal lobe. In this study, twenty patients with unilateral temporal lobe epilepsy and HS were studied with 3 T MRI including T1 MP2RAGE and DTI/DMI sequences. Anterior temporal lobe white matter T1 relaxation times and diffusion measures were analyzed on the HS side, on the contralateral side, and in 10 normal controls. Resected brain tissue of three patients without GMB and four patients with GMB was evaluated ultrastructurally regarding axon density and diameter, the relation of the axon diameter to the total fiber diameter (G-ratio), and the thickness of the myelin sheath. Hippocampal sclerosis GMB of the anterior temporal lobe was related to prolonged T1 relaxation and axonal loss. A less pronounced reduction in axonal fraction was also found on imaging in GMB-negative temporal poles compared with normal controls. Contralateral values did not differ significantly between patients and normal controls. Reduced axonal density and axonal diameter were histopathologically confirmed in the temporopolar white matter with GMB compared to temporal poles without. These results confirm that GMB can be considered an imaging correlate for disturbed axonal maturation that can be quantified with advanced diffusion imaging.

Contrast Bolus Interference in a Multimodal CT Stroke Protocol.

BACKGROUND AND PURPOSE: Whether CTP is performed before or after CTA varies within multimodal CT stroke protocols. CTA after CTP might show venous filling, and CTP metrics might be disturbed by prior CTA. Therefore, we compared CTP metrics conducted before and after CTA in a large cohort of patients with stroke and analyzed interferences of the CTA bolus with the CTP measurement. MATERIALS AND METHODS: We analyzed 1980 patients (368 patients with CTP performed before CTA [group A] versus 1612 patients with CTP performed after [group B]) in a retrospective study. Mean curves, histograms of CTP baseline Hounsfield units, CBF, CBV, time-to-maximum, hypoperfusion, and core volumes were calculated using the software VEOcore. CTA and CTP interferences were analyzed, and a detection and correction method was proposed. RESULTS: Mean CTP baseline values were significantly different in both groups (41 versus 45 HU within the groups A and B, respectively). However, perfusion metrics, hypoperfusion, and core volumes yielded no significant differences. In 49 patients, the descending flank of the CTA bolus interfered with the baseline of the CTP measurement, leading to erroneously low CBV values. These errors vanished when a correction method was applied. CONCLUSIONS: CTP can be reliably performed after CTA without a relevant net effect on perfusion metrics. However, when measuring CTP after CTA, either a short pause on the order of 30 seconds should be observed or an appropriate correction method should be applied. It may help to avoid excluding patients from mechanical thrombectomy by overestimating infarct cores.

X-ray quasi-periodic eruptions from two previously quiescent galaxies.

Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei1,2. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either serendipitously or in archival data1,2, with emission lines in their optical spectra classifying their nuclei as hosting an actively accreting supermassive black hole3,4. Here we report observations of QPEs in two further galaxies, obtained with a blind and systematic search of half of the X-ray sky. The optical spectra of these galaxies show no signature of black hole activity, indicating that a pre-existing accretion flow that is typical of active galactic nuclei is not required to trigger these events. Indeed, the periods, amplitudes and profiles of the QPEs reported here are inconsistent with current models that invoke radiation-pressure-driven instabilities in the accretion disk5-9. Instead, QPEs might be driven by an orbiting compact object. Furthermore, their observed properties require the mass of the secondary object to be much smaller than that of the main body10, and future X-ray observations may constrain possible changes in their period owing to orbital evolution. This model could make QPEs a viable candidate for the electromagnetic counterparts of so-called extreme-mass-ratio inspirals11-13, with considerable implications for multi-messenger astrophysics and cosmology14,15.

A bright γ-ray flare interpreted as a giant magnetar flare in NGC 253.

Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak luminosities1 of 1036 to 1043 erg per second. Occasionally, a giant flare with an energy of around 1044 to 1046 erg is emitted2. These phenomena are thought to arise from neutron stars with extremely high magnetic fields (1014 to 1015 gauss), called magnetars1,3,4. A portion of the second-long initial pulse of a giant flare in some respects mimics short γ-ray bursts5,6, which have recently been identified as resulting from the merger of two neutron stars accompanied by gravitational-wave emission7. Two γ-ray bursts, GRB 051103 and GRB 070201, have been associated with giant flares2,8-11. Here we report observations of the γ-ray burst GRB 200415A, which we localized to a 20-square-arcmin region of the starburst galaxy NGC 253, located about 3.5 million parsecs away. The burst had a sharp, millisecond-scale hard spectrum in the initial pulse, which was followed by steady fading and softening over 0.2 seconds. The energy released (roughly 1.3 × 1046 erg) is similar to that of the superflare5,12,13 from the Galactic soft γ-ray repeater SGR 1806-20 (roughly 2.3 × 1046 erg). We argue that GRB 200415A is a giant flare from a magnetar in NGC 253.

Chicken adaptive response to low energy diet: main role of the hypothalamic lipid metabolism revealed by a phenotypic and multi-tissue transcriptomic approach.

BACKGROUND: Production conditions of layer chicken can vary in terms of temperature or diet energy content compared to the controlled environment where pure-bred selection is undertaken. The aim of this study was to better understand the long-term effects of a 15%-energy depleted diet on egg-production, energy homeostasis and metabolism via a multi-tissue transcriptomic analysis. Study was designed to compare effects of the nutritional intervention in two layer chicken lines divergently selected for residual feed intake. RESULTS: Chicken adapted to the diet in terms of production by significantly increasing their feed intake and decreasing their body weight and body fat composition, while their egg production was unchanged. No significant interaction was observed between diet and line for the production traits. The low energy diet had no effect on adipose tissue and liver transcriptomes. By contrast, the nutritional challenge affected the blood transcriptome and, more severely, the hypothalamus transcriptome which displayed 2700 differentially expressed genes. In this tissue, the low-energy diet lead to an over-expression of genes related to endocannabinoid signaling (CN1R, NAPE-PLD) and to the complement system, a part of the immune system, both known to regulate feed intake. Both mechanisms are associated to genes related polyunsaturated fatty acids synthesis (FADS1, ELOVL5 and FADS2), like the arachidonic acid, a precursor of anandamide, a key endocannabinoid, and of prostaglandins, that mediate the regulatory effects of the complement system. A possible regulatory role of NR1H3 (alias LXRα) has been associated to these transcriptional changes. The low-energy diet further affected brain plasticity-related genes involved in the cholesterol synthesis and in the synaptic activity, revealing a link between nutrition and brain plasticity. It upregulated genes related to protein synthesis, mitochondrial oxidative phosphorylation and fatty acid oxidation in the hypothalamus, suggesting reorganization in nutrient utilization and biological synthesis in this brain area. CONCLUSIONS: We observed a complex transcriptome modulation in the hypothalamus of chicken in response to low-energy diet suggesting numerous changes in synaptic plasticity, endocannabinoid regulation, neurotransmission, lipid metabolism, mitochondrial activity and protein synthesis. This global transcriptomic reprogramming could explain the adaptive behavioral response (i.e. increase of feed intake) of the animals to the low-energy content of the diet.

Immunome differences between porcine ileal and jejunal Peyer's patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues.

The epithelium of the intestinal mucosa and the gut-associated lymphoid tissues (GALT) constitute an essential physical and immunological barrier against pathogens. In order to study the specificities of the GALT transcriptome in pigs, we compared the transcriptome profiles of jejunal and ileal Peyer's patches (PPs), mesenteric lymph nodes (MLNs) and peripheral blood (PB) of four male piglets by RNA-Seq. We identified 1,103 differentially expressed (DE) genes between ileal PPs (IPPs) and jejunal PPs (JPPs), and six times more DE genes between PPs and MLNs. The master regulator genes FOXP3, GATA3, STAT4, TBX21 and RORC were less expressed in IPPs compared to JPPs, whereas the transcription factor BCL6 was found more expressed in IPPs. In comparison between IPPs and JPPs, our analyses revealed predominant differential expression related to the differentiation of T cells into Th1, Th2, Th17 and iTreg in JPPs. Our results were consistent with previous reports regarding a higher T/B cells ratio in JPPs compared to IPPs. We found antisense transcription for respectively 24%, 22% and 14% of the transcripts detected in MLNs, PPs and PB, and significant positive correlations between PB and GALT transcriptomes. Allele-specific expression analyses revealed both shared and tissue-specific cis-genetic control of gene expression.

Measuring HIV- and TB-related stigma among health care workers in South Africa: a validation and reliability study.

SETTING: Recent evidence indicates that human immunodeficiency virus (HIV) and tuberculosis (TB) related stigma act as a key barrier to the utilisation of associated occupational health services by South African health care workers (HCWs). It also highlights a dearth of appropriate tools to measure HIV and TB stigma among HCWs. OBJECTIVE: To test four scales measuring different aspects of stigma: respondent's external stigma (RES) and others' external stigma (OES) towards TB as well as HIV across different professional categories of HCWs. DESIGN: The current study employs data from a study on HIV and TB stigma among HCWs, a cluster randomised controlled trial for the collection of data among 882 HCWs in the Free State Province of South Africa. Confirmatory factor analyses and structural equation modelling were used to assess the validity and reliability of the scales. RESULTS: All four scales displayed adequate internal construct validity. Subsequent analysis demonstrated that all four scales were metric-invariant, and that the OES scales were even scalar-invariant across patient and support staff groups. The scales displayed good reliability and external construct validity. CONCLUSION: Our results support the use of the scales developed to measure TB and HIV stigma among HCWs. Further research is, however, needed to fine tune the instruments and test them across different resource-limited countries.

Stigma as a barrier to the use of occupational health units for tuberculosis services in South Africa.

SETTING: Tuberculosis (TB) is the leading cause of death in South Africa, and health care workers (HCWs) are disproportionally affected. The resulting absenteeism strains the already overburdened health system. Although hospital occupational health care units (OHUs) are cost-effective and of crucial importance in tackling the TB epidemic, the fear of being stigmatised by other colleagues might lead HCWs to avoid using OHUs. OBJECTIVE: To investigate whether the perception of TB stigma among colleagues has a negative effect on the willingness to use OHUs for TB services. DESIGN: In the Free State Province, South Africa, a representative sample of 804 HCWs from six hospitals were surveyed on workplace stigma as a predictor for the use of OHUs for TB services. Applying structural equation modelling, we also controlled for exogenous variables. RESULTS: There was a significant negative relationship between the perception of stigmatising attitudes and behaviours among co-workers and the use of OHUs for TB screening (ß -0.21, P = 0.000), treatment (ß -0.16, P = 0.001) and isoniazid preventive therapy (ß -0.17, P = 0.000). CONCLUSION: The negative effect of TB stigma on OHU use among HCWs can impact upon their health and increase hospital costs. This needs to be addressed by interventions combating TB stigma among HCWs in the workplace.

A Correlation of the Platelet Count with D-Dimer Levels as an Indicator for Component Therapy in Children with Dengue Hemorrhagic Fever.

Dengue Fever (DF) may evolve into two life threatening forms-Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). DHF is associated with increased vascular permeability and plasma leakage causing thrombocytopenia and loss of clotting factors into the third space and may result in bleeding initially due to thrombocytopenia and later due to disseminated intravascular coagulation (DIC), often as a terminal event. Prompt recognition and treatment of minor bleeds in DF children with incipient DIC with component therapy may be associated with improved survival while failure to do so is usually catastrophic. A sensitive marker for early DIC is the presence of D-dimer (DD) in the blood. To determine the correlation between the severity of thrombocytopenia and early DIC in children with DHF. The impact of additional factors like age and shock will also be evaluated. Case control prospective study of 60 DHF sero -positive children (1-15 years) with thrombocytopenia. After clinical evaluation they were divided into two equal groups based on the degree of thrombocytopenia (more than/less than 30,000/mm3). PT/APTT and DD levels were estimated in all children of both groups and statistical correlation was done. There was no significant difference in the DD levels between the two groups. However, children in either group, presenting with clinical features of shock and thrombocytopenia had significantly higher DD levels. Empirical component therapy in children with DHF based purely on their low platelet counts may not be justified. However, in DHF children with thrombocytopenia and features of shock, aggressive component therapy may prevent subsequent bleeding and may be justified.

Stability of edentulous, atrophic mandibles after insertion of different dental implants. A biomechanical study.

OBJECTIVES: Fractures of the atrophic edentulous mandible are a rare complication that can become severe after the insertion of dental implants. This in vitro study investigated the effects of different implant settings varying in number, diameter, and length. and the influence of a fixed bar. MATERIALS AND METHODS: In biomechanical experiments on artificial mandibles, an unmodified reference group, four implant settings with two different implants, and the effect of adding a fixed bar to these settings were tested. All specimens were loaded with incisal biting forces until failure due to fracture. RESULTS: Implants weakened all specimens significantly compared with those in the reference group. Without a fixed bar, four short and thick implants showed the best results, with high significance. With a fixed bar, four long and thin implants withstood the highest loads. The addition of fixed bars reduced the differences between the implant settings. Fixed bars did not show increased stability for all groups; however, these groups showed a higher mean strength. CONCLUSIONS: Four implants with a short and thick design should be the first choice when implants are placed without a fixed bar in an atrophic mandible. With a fixed bar, four long and thin implants should be used.

Analysis of computer-aided techniques for virtual planning in nasoalveolar moulding.

We compared two methods of planning virtual alveolar moulding as the first step in nasoalveolar moulding to provide the basis for an automated process to fabricate nasoalveolar moulding appliances by using computer-assisted design and computer-aided manufacturing (CAD/CAM). First, the initial intraoral casts taken from seven newborn babies with complete unilateral cleft lip and palate were digitised. This was repeated for the target models after conventional nasoalveolar moulding had been completed. The initial digital model for each patient was then virtually modified by two different modelling techniques to achieve the corresponding target model: parametric and freeform modelling with the software Geomagic(®). The digitally-remodelled casts were quantitatively compared with the actual target model for each patient, and the comparison between the two modified models and the target model showed that freeform modelling of the initial cast was successful (mean (SD) deviation n=7, +0.723 (0.148) to -0.694 (0.157)mm) but needed continuous orientation and was difficult to automate. The results from the parametric modelling (mean (SD) deviation, n=7, +1.168 (0.185) to -1.067 (0.221)mm) were not as good as those from freeform modelling. During parametric modelling, we found some irregularities on the surface, and transverse growth of the maxilla was not accounted for. However, this method seems to be the right one as far as automation is concerned. In addition, an external algorithm must be implemented because the function of the commercial software is limited.

Looking beyond the obvious: an unusual cause of iron deficiency anaemia.

Iron deficiency anaemia (IDA) is the most common haematological disorder seen in childhood. While poor intake of iron is the most common cause of IDA, a diligent search must be made to exclude other causes. We present a 5 year old girl who had recurrent hospital admissions for chest infection, radiographic evidence of bilateral pulmonary infiltrates and severe IDA. When she failed to respond to repeated courses of antibiotics, anti tubercular and parenteral and oral iron therapy, a lung biopsy was done which revealed blood and hemosiderophages within the alveoli. Further investigations were suggestive of SLE (dsDNA positivity). A diagnosis of SLE induced alveolar haemorrhage was made and therapy with glucocorticoids was initiated. She has responded well to therapy.