Reducing ischaemic damage in rodent ovarian xenografts transplanted into granulation tissue

BACKGROUND: Anti-cancer therapies frequently lead to ovarian damage and impaired fertility. To preserve fertility, cryopreservation and subsequent transplantation of the ovaries have been suggested. One of the challenges in ovarian graft transplantation is overcoming the initial ischaemic damage that depletes a significant fraction of the oocyte pool. METHODS AND RESULTS: Follicular survival in ovarian grafts was examined by magnetic resonance imaging (MRI) and fluorescence microscopy in a model system in which rat ovaries were transplanted into nude mice. Transplantation into angiogenic granulation tissue created during wound healing shortened the ischaemic period by 24 h and significantly increased the pool of healthy primordial follicles and the perfused area of the transplanted grafts. Functional blood vessels were detected within the grafts as early as 2 days after transplantation. Gain of function was demonstrated both by growth of the grafts and by the hormonal influence on the host uteri. CONCLUSION: Implantation of ovarian grafts into an angiogenic granulation tissue improved graft vascularization and follicular survival. This procedure/treatment may be used for reducing the ischaemic damage in ovarian transplants, thus prolonging graft functionality and increasing the yield of oocytes that can be easily recovered for fertilization.     

Structural characterization of the E2 glycoprotein from Sindbis by lysine biotinylation and LC-MS/MS

Sindbis is an Alphavirus capable of infecting and replicating in both vertebrate and invertebrate hosts. Mature Sindbis virus particles consist of an inner capsid surrounded by a host-derived lipid bilayer, which in turn is surrounded by a protein shell consisting of the E1 and E2 glycoproteins. While a homolog of the E1 glycoprotein has been structurally characterized, the amount of structural data on the E2 glycoprotein is considerably less. In this study, the organization of the E2 glycoprotein was probed by surface biotinylation of intact virions. The virus remained fully infectious, demonstrating that the biotinylation did not alter the topology of the proteins involved in infection. Seven sites of modification were identified in the E2 glycoprotein (K70, K76, K97, K131, K149, K202, and K235), while one site of modification in the E1 glycoprotein (K16) was identified, confirming that the E1 protein is almost completely buried in the virus structure.     

Attentional bias as trait: correlations with novelty seeking

Pseudoneglect is traditionally viewed as reflecting right hemisphere specialization for processing spatial information, which brings about relatively greater activation of the right hemisphere and orienting towards the contralateral space. Such interpretation implies that the leftward attentional bias is a population trait. Animal studies, however, suggest that orienting bias is a trait of the individual and individual differences in the direction and magnitude of this orienting bias reflect individual differences in asymmetry in dopaminergic brain systems, which are also reflected in other behavioral differences. The present study was designed to test the hypothesis that healthy individuals show consistent attentional bias, the direction and magnitude of which varies among individuals and is associated with the degree of novelty seeking, a temperament trait associated with dopamine asymmetry. Forty-nine right-handed participants performed the greyscales task on two separate occasions and completed the Tridimensional Personality Questionnaire. Although on average some degree of leftward attentional bias was observed on both occasions, both the direction and the magnitude of the bias differed greatly, with some individuals showing a strong leftward bias whereas others showed a strong rightward bias. A highly significant correlation was found between degree and magnitude of this bias on the two testing sessions, supporting the hypothesis that it may reflect an individual trait. As predicted, higher scores on novelty seeking were associated with rightward attentional bias, suggesting that this bias may reflect asymmetries in dopaminergic circuits in healthy individuals.     

Lateralized neuroleptic-induced side effects are associated with asymmetric visual evoked potentials

Recent studies suggest that neuroleptic drugs may have an asymmetric effect on the two cerebral hemispheres. This effect is reflected by emergence of drug-induced lateralized extrapyramidal side effects and by dose-related alterations in electrophysiological asymmetries. The present study examined the hypothesis that asymmetry of visual evoked potentials (VEPs) is associated with lateralized appearance of neuroleptic-induced parkinsonism or tardive dyskinesia (TD). The asymmetry of the amplitudes of later VEP components was significantly higher in patients with lateralized side effects (n = 8) than in patients with symmetrical side effects (n = 6) or free of extrapyramidal side effects (n = 11). The possibility that VEP asymmetry reflects the differential degree to which the two hemispheres are affected by medication is discussed.     

In vivo measurements of lamination patterns in the human cortex

The laminar composition of the cerebral cortex is tightly connected to the development and connectivity of the brain, as well as to function and pathology. Although most of the research on the cortical layers is done with the aid of ex vivo histology, there have been recent attempts to use magnetic resonance imaging (MRI) with potential in vivo applications. However, the high‐resolution MRI technology and protocols required for such studies are neither common nor practical. In this article, we present a clinically feasible method for assessing the laminar properties of the human cortex using standard pulse sequence available on any common MRI scanner. Using a series of low‐resolution inversion recovery (IR) MRI scans allows us to calculate multiple T₁ relaxation time constants for each voxel. Based on the whole‐brain T₁‐distribution, we identify six different gray matter T₁ populations and their variation across the cortex. Based on this, we show age‐related differences in these population and demonstrate that this method is able to capture the difference in laminar composition across varying brain areas. We also provide comparison to ex vivo high‐resolution MRI scans. We show that this method is feasible for the estimation of layer variability across large population cohorts, which can lead to research into the links between the cortical layers and function, behavior and pathologies that was heretofore unexplorable.     

Exposure to amphetamine after substantia nigra lesion interferes with the process of behavioral recovery

Recovery from unilateral substantia nigra lesion may be indicated by re-emergence of circling in the pre-lesion preferred direction. Following 6-OHDA-induced lesion of the dominant SN, we examined: (a) The effect of the delay from lesioning on amphetamine-induced rotation asymmetry, and (b) The effect of early post-lesion exposure to amphetamine on later rotation asymmetry. d-Amphetamine was initially injected either 7, 14, 21, or 30 days after lesioning. Transient circling in pre-lesion preferred direction (contralateral to lesioned side) was more frequently encountered on days 7 and 30 after lesioning, as compared to days 14 and 21. The contralateral rotation observed on day 7 is attributed to degeneration-induced DA release, whereas contralateral rotation noted on day 30 is believed to reflect the operation of post-lesion compensatory processes within the spared DA neurons. In response to subsequent amphetamine administration 30 days after lesioning, rats with previous exposure to the drug circled ipsilaterally, whereas most rats given amphetamine for the first time in that session rotated contralaterally to the lesion. These findings suggest that post-lesion administration of amphetamine interferes with the process of recovery.     

Adopting a culture of remote damage control resuscitation in the military: Insights from the Israel defense forces decade of experience

Background

Remote damage control resuscitation (RDCR) aims to apply the principles of damage control resuscitation to prehospital and austere care, emphasizing early control of compressible hemorrhage, balanced volume resuscitation, and the prevention or correction of coagulopathy, acidosis, hypothermia, and hypocalcemia. Over the past decades, the Israel Defense Forces Medical Corps (IDF-MC) has made significant efforts to integrate the principles of RDCR into prehospital trauma care in the military.

Study Design and Methods

In this article, we reflect on the implementation of RDCR in the prehospital setting by the IDF-MC, sharing successes, challenges, considerations on guideline changes, and their assessment over time.

Results

The implementation of RDCR has resulted in changes in clinical practice guidelines and training programs, with increased awareness and adoption of RDCR principles among both medical and non-medical military personnel. The implementation of these principles and adherence to guideline changes have been analyzed using the Israel Defense Forces Trauma Registry.

Discussion

By sharing our experiences, we hope to provide valuable insights for other military and civilian organizations seeking to adopt similar protocols for prehospital care. Continuous evaluation and refinement of guidelines and training programs will be essential for ongoing implementation and advancement of RDCR in the prehospital setting.     

In vitro,ex vivo,and clinical evaluation of anti-aging gel containing EPA and CBD

Background

Skin aging manifestation, such as coarse wrinkles, loss of elasticity, pigmentation, and rough-textured appearance, is a multifactorial process that can be exacerbated by air pollution, smoking, poor nutrition, and sun exposure. Exposure to UV radiation is considered the primary cause of extrinsic skin aging and accounts for about 80% of facial aging. Extrinsic skin aging signs can be reduced with demo-cosmetic formulations. Both cannabidiol (CBD) and eicosapentaenoic acid (EPA) have been previously suggested as potent active dermatological ingredients.

Aims

The objective of the current research was to evaluate the compatibility of both agents in the prevention and treatment of skin aging. First, the impact of both agents was assessed using standard photoaging models of UV-induced damage, both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Then, a clinical validation study (n = 33) was performed using an optimized topical cream formulation tested at different time points (up to Day 56).

Results

EPA was found to potentiate the protective effects of CBD by reducing the secretion of prostaglandin E2 (PGE₂) and interleukin-8 (IL-8), two primary inflammatory agents associated with photoaging. In addition, a qualitative histological examination signaled that applying the cream may result in an increase in extracellular matrix (ECM) remodeling following UV radiation. This was also evidenced clinically by a reduction of crow's feet wrinkle area and volume, as well as a reduction of fine line wrinkle volume as measured by the AEVA system. The well-established age-dependent subepidermal low-echogenic band (SLEB) was also reduced by 8.8%. Additional clinical results showed significantly reduced red spots area and count, and an increase in skin hydration and elasticity by 31.2% and 25.6% following 56 days of cream application, respectively. These impressive clinical results correlated with high satisfaction ratings by the study participants.

Discussion and Conclusions

Collectively, the results show a profound anti-aging impact of the developed formulation and strengthen the beneficial derm-cosmetic properties of CBD-based products.     

The biomechanical efficacy of a hybrid support surface in protecting supine patients from sacral pressure ulcers

Support surfaces are the most important pressure ulcer/injury prevention technology available to clinicians for protecting their at-risk patients. A hybrid support surface marries the benefits of reactive and active support surfaces, by using high-quality foam material inside inflatable air cells. When used in its “static mode”, it is a constant low air pressure mattress which delivers pressure redistribution in response to patient bodyweight and movements, by maximising the immersion and envelopment performance of the support surface. When used in its powered “dynamic mode”, this system further delivers alternating pressure care via the connected foam and air cells. Modes of action of hybrid support surfaces were never studied quantitatively before, excluding through the limited scope of interface pressure mapping. In this work, we developed a novel computational modelling framework and simulations to visualise and quantify the state of soft tissue loading at the buttocks of a supine patient positioned on a hybrid support surface, in both the static and dynamic modes. We found that the dynamic mode effectively shifts deep concentrated soft tissue loading from under the sacral bone (towards the sacral promontory) to the tip of the sacrum (coccyx) and vice versa, and thereby, generates a deep tissue offloading effect.