-
International Journal of Biological... Jun 2024Targeting delivery to the infection site and good affinity of vehicle to the bacterial are two main concerns in therapy of bacterial infection, and on-demand release of...
Targeting delivery to the infection site and good affinity of vehicle to the bacterial are two main concerns in therapy of bacterial infection, and on-demand release of drug is another important issue. In this work, a liposome drug delivery system (HA/P/BAI-lip) incorporated with baicalein and modified by PHMG and HA was prepared. Several characterizations were conducted to examine the physical properties of liposome. Then it was applied to treatments of MRSA induced dorsal subcutaneous abscess model and the thigh muscle infected model. The presence of guanidine group in HA/P/BAI-lip rendered the liposome satisfactory bacterial target ability and good pH sensitive properties. The lipase secreted by bacterial could promote the hydrolysis of soybean phosphatidylcholine (SPC) in liposome. The modification of HA in HA/P/BAI-lip could lead the drug system to the exact infected site where CD44 was abundant because of inflammation. The low pH microenvironment characteristic of bacterial infection could induce the swelling of liposome following by degradation. Taken together, baicalein could be released selectively at the infected site to exert antibacterial capacity. HA/P/BAI-lip showed impressive antibacterial ability and dramatically decrease the bacterial burden of infection site and alleviate the infiltration of inflammatory cells, facilitating the recovery of infection.
PubMed: 38936579
DOI: 10.1016/j.ijbiomac.2024.133432 -
Behavioural Brain Research Jun 2024The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of...
The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of BOLD activation in hippocampus, iFG and vmPFC, as well as differential resting-state functional connectivity between prefrontal regions and the dorsal attention network. Also, pharmacological modulations of the noradrenergic system that influence attentional processing have partially different effects upon individuals with (REN) and without (NoREN) a propensity for renewal. However, it is as yet unknown whether REN and NoREN individuals differ regarding microstructural properties in attention-related white matter (WM) regions, and whether such differences are related to noradrenergic processing. In this diffusion tensor imaging (DTI) analysis we investigated the relation between microstructural properties of attention-related WM tracts and ABA renewal propensity, under conditions of noradrenergic stimulation by means of the noradrenergic reuptake inhibitor atomoxetine, compared to placebo. Fractional anisotropy (FA) was higher in participants with noradrenergic stimulation (ATO) compared to placebo (PLAC), the effect was predominantly left-lateralized and based on the comparison of ATO REN and PLAC REN participants. In REN participants of both treatment groups, FA in several WM tracts showed a positive correlation with the ABA renewal level, suggesting higher renewal levels were associated with higher microstructural integrity. These findings point towards a relation between microstructural properties of attention-related WM tracts and the propensity for renewal that is not specifically dependent on noradrenergic processing.
PubMed: 38936425
DOI: 10.1016/j.bbr.2024.115125 -
Current Biology : CB Jun 2024Escape behavior is a set of locomotor actions that move an animal away from threat. While these actions can be stereotyped, it is advantageous for survival that they are...
Escape behavior is a set of locomotor actions that move an animal away from threat. While these actions can be stereotyped, it is advantageous for survival that they are flexible. For example, escape probability depends on predation risk and competing motivations, and flight to safety requires continuous adjustments of trajectory and must terminate at the appropriate place and time. This degree of flexibility suggests that modulatory components, like inhibitory networks, act on the neural circuits controlling instinctive escape. In mice, the decision to escape from imminent threats is implemented by a feedforward circuit in the midbrain, where excitatory vesicular glutamate transporter 2-positive (VGluT2) neurons in the dorsal periaqueductal gray (dPAG) compute escape initiation and escape vigor. Here we tested the hypothesis that local GABAergic neurons within the dPAG control escape behavior by setting the excitability of the dPAG escape network. Using in vitro patch-clamp and in vivo neural activity recordings, we found that vesicular GABA transporter-positive (VGAT) dPAG neurons fire action potentials tonically in the absence of synaptic inputs and are a major source of inhibition to VGluT2 dPAG neurons. Activity in VGAT dPAG cells transiently decreases at escape onset and increases during escape, peaking at escape termination. Optogenetically increasing or decreasing VGAT dPAG activity changes the probability of escape when the stimulation is delivered at threat onset and the duration of escape when delivered after escape initiation. We conclude that the activity of tonically firing VGAT dPAG neurons sets a threshold for escape initiation and controls the execution of the flight action.
PubMed: 38936364
DOI: 10.1016/j.cub.2024.05.068 -
Zoology (Jena, Germany) Jun 2024Disproportional changes (i.e. allometry) in shark morphology relative to increasing body size have been attributed to shifts in function associated with niche shifts in...
Disproportional changes (i.e. allometry) in shark morphology relative to increasing body size have been attributed to shifts in function associated with niche shifts in life history, such as in habitat and diet. Photographs of blue sharks (Prionace glauca, 26-145 kg) were used to analyze changes in parameters of body and fin morphology with increasing mass that are fundamental to swimming and feeding. We hypothesized that blue sharks would demonstrate proportional changes (i.e. isometry) in morphology with increasing mass because they do not undergo profound changes in prey and habitat type; accordingly, due to geometric scaling laws, we predicted that blue sharks would grow into bodies with greater turning inertias and smaller frontal and surface areas, in addition to smaller spans and areas of the fins relative to mass, which are parameters that are associated with the swimming performance in sharks. Many aspects of morphology increased with isometry. However, blue sharks demonstrated negative allometry in body density, whereas surface area, volume and roll inertia of the body, area, span and aspect ratio of both dorsal fins, span and aspect ratio of the ventral caudal fin, and span, length and area of the mouth increased with positive allometry. The dataset was divided in half based on mass to form two groups: smaller and larger sharks. Besides area of both dorsal fins, relative to mass, larger sharks had bodies with significantly greater turning inertia and smaller frontal and surface areas, in addition to fins with smaller spans and areas, compared to smaller sharks. In conclusion, isometric scaling does not necessarily imply functional similarity, and allometric scaling may sometimes be critical in maintaining, rather than shifting, function relative to mass in animals that swim through the water column.
PubMed: 38936326
DOI: 10.1016/j.zool.2024.126184 -
Developmental Cognitive Neuroscience Jun 2024Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry....
Adolescent risk-taking has been attributed to earlier-developing motivational neurocircuitry that is poorly controlled by immature executive-control neurocircuitry. Functional magnetic resonance imaging findings of increased ventral striatum (VS) recruitment by reward prospects in adolescents compared to adults support this theory. Other studies found blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy but have never been systematically explored. Adolescents and adults performed a novel reward task that holds constant the expected value of all rewards but varies whether rewards are dependent on vigilance-intensive responding versus making a lucky choice during a relaxed response window. We examined group by sub-task contrast differences in activation of VS and more motoric regions of striatum in response to anticipatory cues. Reward anticipation in both task conditions activated portions of striatum in both groups. In voxel-wise comparison, adults showed greater anticipatory recruitment of VS in trials involving choice during a relaxed time window, not in the more vigilance-demanding trials as hypothesized. In accord with our hypotheses, however, adults showed greater activation in dorsal striatum and putamen volumes of interest during reward anticipation under vigilance-demanding conditions. Following trial outcome notifications, adolescents showed greater activation of the VS during reward notification but lower activation during loss notification. These data extend findings of cross-sectional age-group differences in incentive-anticipatory recruitment of striatum, by demonstrating in adults relatively greater recruitment of motor effector regions of striatum by attentional and motor demands.
PubMed: 38936253
DOI: 10.1016/j.dcn.2024.101412 -
Stem Cell Research Jun 2024Friedreich's ataxia (FRDA) is a rare neurodegenerative disease caused by an expansion of a GAA repeat sequence within the Frataxin (FXN) gene. Prominent regions of...
Generation of genetically modified Friedreich's ataxia induced pluripotent stem cell lines and isogenic control lines carrying an inducible neurogenin-2 expression cassette.
Friedreich's ataxia (FRDA) is a rare neurodegenerative disease caused by an expansion of a GAA repeat sequence within the Frataxin (FXN) gene. Prominent regions of neurodegeneration include sensory neurons within the dorsal root ganglia. Here we present a set of genetically modified FRDA induced pluripotent stem cell (iPSC) lines that carry an inducible neurogenin-2 (NGN2) expression cassette. Exogenous expression of NGN2 in iPSC derived neural crest progenitors efficiently generates functionally mature sensory neurons. These cell lines will provide a streamlined source of FRDA iPSC sensory neurons for studying both disease mechanism and screening potential therapeutics.
PubMed: 38936158
DOI: 10.1016/j.scr.2024.103477 -
The Journal of Hand Surgery Jun 2024To compare the biomechanical properties of adjunctive dorsal spanning plate (DSP) fixation with traditional K-wire fixation of perilunate dislocations in a cadaveric...
PURPOSE
To compare the biomechanical properties of adjunctive dorsal spanning plate (DSP) fixation with traditional K-wire fixation of perilunate dislocations in a cadaveric model.
METHODS
Fourteen fresh-frozen cadaveric wrists underwent simulated perilunate injury. The specimens were randomly allocated to either K-wire fixation versus K-wire and DSP fixation. Scapholunate (SL) ligament repair was performed in all specimens. The constructs were tested using a robot cyclically and to failure. Fluoroscopic images were obtained of the specimens prior to simulated injury, after fixation, after 10 and 100 loading cycles, and at construct failure. Differences in carpal alignment parameters (SL interval, SL angle, lunotriquetral interval, and capitolunate angle) and load to failure were recorded.
RESULTS
There were no statistically significant differences between the two group's carpal alignment parameters after fixation. Specimens fixated with K-wires and DSP required significantly higher loads to achieve construct failure. The only significant difference between the two groups' carpal alignment parameters was SL interval change at failure.
CONCLUSIONS
Compared with K-wire fixation alone, adjunctive DSP fixation resulted in significantly increased loads to failure and decreased change in SL interval at the time of failure.
CLINICAL RELEVANCE
Adjunctive DSP may be a useful technique in the polytraumatized patient in whom providing back a weight-bearing extremity may be advantageous in the rehabilitation process.
PubMed: 38934992
DOI: 10.1016/j.jhsa.2024.04.016 -
Indian Journal of Dental Research :... Jan 2024This case report presents a rare combination of congenital anomalies in an otherwise healthy male infant born at 36 weeks. The infant was diagnosed with congenital...
RATIONALE
This case report presents a rare combination of congenital anomalies in an otherwise healthy male infant born at 36 weeks. The infant was diagnosed with congenital maxillomandibular synechia, ectrodactyly, and ankyloglossia superior syndrome (ASS).
PATIENT CONCERNS
Inability to open the mouth completely, feeding challenges, and a cleft palate. The infant was stabilized through successful positive pressure ventilation via a face mask at birth and enteral feeding was initiated via a feeding gastrostomy.
EXAMINATION
Diagnostic tests revealed a midline palatal cleft, hypoplastic jaws, persistent metopic suture, and a bony fusion at the midline.
TREATMENT
Sectioning of the bony spur along the midline and achieving a mouth opening of 2 cm post-manipulation. The patient is under follow-up, with future treatment plans including cleft palate correction at 12 months and potential frontomandibular and lower jaw advancement depending on growth trajectories.
TAKEAWAY LESSONS
This case underscores the complexity of managing multiple congenital anomalies and the need for individualized treatment plans.
Topics: Humans; Male; Cleft Palate; Tongue; Palate, Hard; Infant, Newborn; Abnormalities, Multiple; Maxilla; Ankyloglossia; Jaw Abnormalities; Mandible
PubMed: 38934763
DOI: 10.4103/ijdr.ijdr_961_23 -
Equine Veterinary Journal Jun 2024Surgical treatment options for horses with overriding dorsal spinous processes include interspinous ligament desmotomy and partial spinous process ostectomy. The impact...
BACKGROUND
Surgical treatment options for horses with overriding dorsal spinous processes include interspinous ligament desmotomy and partial spinous process ostectomy. The impact of spinal surgery on the three-dimensional biomechanics of the equine thoracolumbar spine and the epaxial musculature is unclear.
OBJECTIVES
To investigate the influence of interspinous ligament desmotomy and cranial wedge ostectomy on the biomechanics of the equine thoracolumbar spine and the paraspinal Musculi multifidi.
STUDY DESIGN
Ex-vivo experiments.
METHODS
Twelve equine thoracolumbar spine specimens were mounted in a custom-made mechanical test rig. Based on computed tomographic imaging, distances between dorsal spinous processes and the spinal range of motion (lateral bending, axial rotation, flexion, extension) were compared before and after desmotomy and cranial wedge ostectomy performed at two or five surgical sites. Anatomical dissection was subsequently conducted to document surgical trauma to the Musculi multifidi following desmotomy.
RESULTS
The distance between spinous processes in neutral position did not increase significantly after desmotomy (median preoperative = 7.2 mm, interquartile range [IQR] = 3.6 mm; median postoperative = 7.4 mm, IQR = 3.7 mm; p = 0.09), but increased significantly after ostectomy (median preoperative = 8.8 mm, IQR = 4.2 mm; median postoperative = 13 mm, IQR = 6.1 mm; p < 0.001). Both surgical procedures significantly increased the rotational spinal range of motion (p = 0.001), particularly at the level T14/T15 (median preoperative = 6.4°, IQR = 3.2°; median postoperative = 8.2°, IQR = 3.5°; increase = 28.1%; p = 0.02). Musculi multifidi injury was evident at all desmotomy sites.
MAIN LIMITATIONS
Ex-vivo study with limited sample size.
CONCLUSIONS
Neither interspinous ligament desmotomy nor cranial wedge ostectomy resulted in an increased range of motion during flexion, extension or lateral bending but both procedures influenced the rotational component of the equine thoracolumbar spinal mobility.
PubMed: 38934728
DOI: 10.1111/evj.14123 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that...
In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that obesogenic high-fat and sugar diet intake during adolescence (adoHFSD) impairs hippocampus (HPC)-dependent memory in rodents. These results were obtained in males only and it remains to evaluate whether adoHFSD has similar effect in females. Therefore, here, we investigated the effects of adoHFSD consumption on HPC-dependent contextual fear memory and associated brain activation in male and female mice. Exposure to adoHFSD increased fat mass accumulation and glucose levels in both males and females but impaired contextual fear memory only in males. Compared with females, contextual fear conditioning induced higher neuronal activation in the dorsal and ventral HPC (CA1 and CA3 subfields) as well as in the medial prefrontal cortex in males. Also, adoHFSD-fed males showed enhanced c-Fos expression in the dorsal HPC, particularly in the dentate gyrus, and in the basolateral amygdala compared with the other groups. Finally, chemogenetic inactivation of the dorsal HPC rescued adoHFSD-induced memory deficits in males. Our results suggest that males are more vulnerable to the effects of adoHFSD on HPC-dependent aversive memory than females, due to overactivation of the dorsal HPC.
Topics: Animals; Fear; Male; Female; Hippocampus; Diet, High-Fat; Obesity; Sex Characteristics; Mice; Memory; Mice, Inbred C57BL; Prefrontal Cortex
PubMed: 38934712
DOI: 10.1093/cercor/bhae254