Correction: A Review of Medical Student First-Author Publications in Plastic Surgery.

[This corrects the article DOI: 10.7759/cureus.43025.].

Epigenetic inheritance of phenotypes associated with parental exposure to cocaine.

Parental exposure to drugs of abuse induces changes in the germline that can be transmitted across subsequent generations, resulting in enduring effects on gene expression and behavior. This transgenerational inheritance involves a dynamic interplay of environmental, genetic, and epigenetic factors that impact an individual's vulnerability to neuropsychiatric disorders. This chapter aims to summarize recent research into the mechanisms underlying the inheritance of gene expression and phenotypic patterns associated with exposure to drugs of abuse, with an emphasis on cocaine. We will first define the epigenetic modifications such as DNA methylation, histone post-translational modifications, and expression of non-coding RNAs that are impacted by parental cocaine use. We will then explore how parental cocaine use induces heritable epigenetic changes that are linked to alterations in neural circuitry and synaptic plasticity within reward-related circuits, ultimately giving rise to potential behavioral vulnerabilities. This discussion will consider phenotypic differences associated with gestational as well as both maternal and paternal preconception drug exposure and will emphasize differences based on offspring sex. In this context, we explore the complex interactions between genetics, epigenetics, environment, and biological sex. Overall, this chapter consolidates the latest developments in the multigenerational effects and long-term consequences of parental substance abuse.

A novel in vitro model of clinical cryoablation to investigate the transition zone for focal tumor ablation.

Cryoablation (CA) of solid tumors is highly effective at reducing tumor burden and eliminating small, early stage tumors. However, complete ablation is difficult to achieve and cancer recurrence is a significant barrier to treatment of larger tumors compared to resection. In this study, we explored the relationship between temperature, ice growth, and cell death using a novel in vitro model of clinical CA with the Visual-ICE (Boston Scientific) system, a clinically approved and widely utilized device. We found that increasing the duration of freezing from 1 to 2 min increased ice radius from 3.44 ± 0.13 mm to 5.29 ± 0.16 mm, and decreased the minimum temperature achieved from -22.8 ± 1.3 °C to -45.5 ± 7.9 °C. Furthermore, an additional minute of freezing increased the amount of cell death within a 5 mm radius from 42.5 ± 8.9% to 84.8 ± 1.1%. Freezing at 100% intensity leads to faster temperature drops and a higher level of cell death in the TRAMP-C2 mouse prostate cancer cell line, while lower intensities are useful for slow freezing, but result in less cell death. The width of transition zone between live and dead cells decreased by 0.4 ± 0.2 mm, increasing from one to two cycles of freeze/thaw cycles at 100% intensity. HMGB-1 levels significantly increased with 3 cycles of freeze/thaw compared to the standard 2 cycles. Overall, a longer freezing duration, higher freezing intensity, and more freeze thaw cycles led to higher levels of cancer cell death and smaller transition zones. These results have the potential to inform future preclinical research and to improve therapeutic combinations with CA.

Use of a novel magnetically actuated compression system to study the temporal dynamics of axial and lateral strain in human osteochondral plugs.

The high water content of articular cartilage allows this biphasic tissue to withstand large compressive loads through fluid pressurization. The system presented here, termed the "MagnaSquish", provides new capabilities for quantifying the effect of rehydration on cartilage behavior during cyclic loading. An imbalanced rate of fluid exudation during load and fluid re-entry during recovery can lead to the accumulation of strain during successive loading cycles - a phenomenon known as ratcheting. Typical experimental systems for cartilage biomechanics use continuous contact between the platen and sample, which may affect tissue rehydration by compressing the top layer of cartilage and slowing fluid re-entry. To address this limitation, we developed a magnetically actuated device that provides full lift-off of the platen in between loading cycles. We investigated strain accumulation in cadaveric human osteochondral plugs during 750 loading cycles, with two dimensional profiles of the cartilage captured at 30 frames per second throughout loading and 10 min of additional free swelling recovery. Axial and lateral strain measurements were extracted from the tissue profiles using a UNet-based deep learning algorithm to circumvent manual tracing. We observed increased axial strain accumulation with shorter inter-cycle recovery, with static loading serving as the extreme case of zero recovery. The loading waveform during the 750 cycles dictated the pace of the recovery during the extended free swelling period, as shorter inter-cycle recovery led to more persistent axial strain accumulation for up to five minutes. This work showcases the importance of fluid re-entry in resisting strain accumulation during cyclical compression.

Charcot Arthropathy of the Digit: A Report of 2 Cases.

CASE: Charcot arthropathy (CA) is a progressive degenerative joint disease typically affecting lower extremity weight-bearing joints, with only a few cases reported in the fingers. We present 2 cases of interphalangeal joint CA: the long finger distal interphalangeal joint in a 73-year-old man with severe carpal tunnel syndrome and the ring finger proximal interphalangeal joint of a 71-year-old woman with diabetic neuropathy. CONCLUSION: Two cases of CA of the digits were treated with splinting with resolution of symptoms and no wound complications.

30-Day Post-Operative Complications of Facial Fracture Repairs: A United States Database Study.

Study Design: Cross-sectional database analysis. Objective: To define post-operative complication rates in facial fracture repair and to assess this data for patient characteristics which may be associated with post-operative complications. Methods: We performed a retrospective cohort analysis of the National Surgical Quality Improvement Program (NSQIP) database between January 1, 2015, and December 31, 2019. All patients included in this study sample must have (a) been ≥18 years old and (b) underwent surgical repair of a facial fracture during the study period by a plastic surgeon or otolaryngologist. Adverse outcomes at 30 days were characterized into four groups: superficial surgical site infection (SSI), deep SSI, organ space infection, and wound disruption. Results: In total, 2481 patients met the primary outcome of facial fracture. Among the four fracture types assessed, 1090 fractures (43.9%) were mandibular, 721 were zygomatic (29.1%), 638 were orbital (25.7%), and 32 (1.3%) were Lefort. Of the entire cohort, 25 patients (1.01%) experienced a superficial SSI, 14 patients (.56%) presented with a deep SSI, 25 fractures (1.01%) returned with an organ space infection, and 23 patients (.93%) experienced some type of wound disruption. Smokers had a significantly higher risk of superficial SSIs (P < .05) and organ space infections (P < .05). Conclusions: The majority of facial fracture patients do not experience post-operative complications. However, smokers and patients with diabetes mellitus were shown to be at an elevated risk of developing complications. Future research should further investigate this relationship and focus on developing interventions to improve post-operative outcomes.

Prenatal diagnosis of Hartsfield syndrome with a novel genetic variant.

A G2P0, 24-year-old woman presented at 17 weeks 3 days gestation for a fetal anatomy scan. Ultrasound identified bilateral upper and lower extremity ectrodactyly, semilobar holoprosencephaly, midface hypoplasia, and cleft lip and palate. Amniocentesis for a chromosome microarray demonstrated no significant copy number changes. Whole exome sequencing was subsequently completed, which revealed a de novo, likely pathogenic variant in FGFR1, c.2044G>A (D682N), consistent with FGFR1-related Hartsfield syndrome. This case highlights the first presumed molecularly confirmed prenatal diagnosis of Hartsfield syndrome and identifies a new pathogenic variant.

Sex-dependent fear memory impairment in cocaine-sired rat offspring.

Cocaine self-administration by male rats results in neuronal and behavioral alterations in offspring, including responses to cocaine. Given the high degree of overlap between the brain systems underlying the pathological responses to cocaine and stress, we examined whether sire cocaine taking would influence fear-associated behavioral effects in drug-naïve adult male and female progeny. Sire cocaine exposure had no effect on contextual fear conditioning or its extinction in either male or female offspring. During cued fear conditioning, freezing behavior was enhanced in female, but not male, cocaine-sired progeny. In contrast, male cocaine-sired progeny exhibited enhanced expression of cue-conditioned fear during extinction. Long-term potentiation (LTP) was robust in the basolateral amygdala (BLA), which encodes fear conditioning, of female offspring but was completely absent in male offspring of cocaine-exposed sires. Collectively, these results indicate that cued fear memory is enhanced in the male progeny of cocaine exposed sires, which also have BLA synaptic plasticity deficits.

A Review of Medical Student First-Author Publications in Plastic Surgery.

The integrated plastic surgery residency match is a highly competitive process. If performed wisely, medical research is an opportunity to differentiate applications from peers, and productivity is closely evaluated by residency programs. In this study, the authors aimed to characterize medical student research productivity for integrated plastic surgery residency programs and their respective medical schools. To this end, the authors performed a retrospective review of senior author publications from the 81 integrated plastic surgery programs from January 1, 2016, to December 31, 2020. The primary outcome was a publication with a medical student as the first author. Secondary outcomes included the number of faculty from each program, the geographic region of the program, and the ranking of associated medical schools. It was found that the average number of medical student first-author publications and faculty members per institution were 14.0 and 11.0, respectively. There was a positive correlation between the number of faculty members and several medical student first-author publications for a program (R = 0.54, P < 0.0001). The average number of medical student first-author publications was higher in the top 25 programs than for the remaining programs (P < 0.001), and most medical student first-author publications in the United States were produced by 10 plastic surgery programs. From these findings, it was concluded that these programs associated with higher-ranking medical schools produce greater numbers of medical student first-author publications. These analyses of medical student academic productivity should be a highly useful guide for current and future medical students as they strategize their successful match into plastic surgery.

Addiction neuroscience goes nuclear: A role for the transcription factor RXRα.

Building on work defining the cocaine-modulated transcriptional landscape in mice, Godino and colleagues focus in this issue of Neuron1 on the role of a specific nuclear receptor, RXRα. Results demonstrate that modifying accumbens RXRα expression profoundly alters gene transcription, neuronal activity, and cocaine-induced behavioral responses.

Public perspective on medications to delay Alzheimer's disease symptoms.

Disease-modifying treatments for Alzheimer's disease are emerging. Our research examined how personal risk for AD may influence intentions to ask for medications to delay symptoms of AD, and how the availability of such medications impacts interest in AD-related genetic testing. Invitations to a web-based survey were posted on social media sites. Respondents were sequentially assigned to imagine that they had a 5%, 15%, or 35% chance of developing AD. They were then provided a hypothetical scenario describing a medication that delayed AD symptoms. After reporting intentions to ask for the medication, respondents were asked about their interest in genetic testing to predict AD risk. Data from 310 individuals were analyzed. Intentions to ask for a preventative medication were greater for respondents presented AD risks of 35% compared to risks of 15% and 5% (86% vs. 66% vs. 62%, respectively, p < 0.001). The proportion who would ask for genetic susceptibility testing increased from 58% to 79% when respondents were told to imagine that a medication that delayed AD symptoms existed (p < 0.001). Findings suggest that individuals who know they have an increased risk for AD are more likely pursue medications to delay onset of disease symptoms, and the availability of AD-delaying treatments will increase interest in associated genetic testing. Findings provide insight about who will pursue emerging preventative medications, including individuals for whom the medications may be inappropriate, and the impact on genetic test utilization.

CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles.

Activation of voltage-gated calcium channels at presynaptic terminals leads to local increases in calcium and the fusion of synaptic vesicles containing neurotransmitter. Presynaptic output is a function of the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at Caenorhabditis elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters ~250 nm in diameter with the active zone proteins Neurexin, α-Liprin, SYDE, ELKS/CAST, RIM-BP, α-Catulin, and MAGI1. CaV2 channels are colocalized with the priming protein UNC-13L and mediate the fusion of vesicles docked within 33 nm of the dense projection. CaV2 activity is amplified by ryanodine receptor release of calcium from internal stores, triggering fusion up to 165 nm from the dense projection. By contrast, CaV1 channels are dispersed in the synaptic varicosity, and are colocalized with UNC-13S. CaV1 and ryanodine receptors are separated by just 40 nm, and vesicle fusion mediated by CaV1 is completely dependent on the ryanodine receptor. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.

Likelihood of Craniofacial Injury and Hospitalization with Alcohol Use While Skateboarding and Scootering.

Study Design: We designed a cross-sectional epidemiologic study to evaluate the influence of substance use on craniofacial injuries in a population of skateboard and scooter users. Objective: The primary outcome of our study was craniofacial injury. The secondary outcome was hospitalization. Methods: We report a cross-sectional study of patients reported to the National Electronic Injury Surveillance System (NEISS) from January 1, 2019, to December 31, 2020, in the United States. Patients were included in our study if they were evaluated in the emergency department (ED) for a skateboard- or scooter-related injury. Results: There were over 5396 total patients who presented to a NEISS-participating ED after skateboard- or scooter- related trauma during the study period. There were 1136 patients with a craniofacial injury (primary endpoint), and patients under the influence of alcohol or drugs had greater odds of experiencing a craniofacial injury than those not under the influence (odds ratio [OR]: 4.16, 95% confidence interval [CI]: 3.24-5.32, P < .0001). Four hundred-thirty patients were hospitalized (secondary endpoint), and patients under the influence had greater odds of being hospitalized than those not under the influence (OR: 2.83, 95% CI: 2.04-3.91, P < .0001). Conclusions: Alcohol and drug use while skateboarding or scootering drastically increases the likelihood of craniofacial injury and subsequent hospitalization and should be avoided whenever possible. The importance of wearing a helmet while operating these devices cannot be overstated.

Low frequency optogenetic deep brain stimulation of nucleus accumbens dopamine D1 or D2 receptor-containing neurons attenuates cocaine seeking selectively in male rats in part by reversing synaptic plasticity deficits.

Background: Clinically, deep brain stimulation (DBS) utilizes relatively high frequencies (>100 Hz). In preclinical models, 160 Hz stimulation of the nucleus accumbens in rodents prevents relapse of drug seeking. However, the ability of varied frequencies of accumbens DBS to attenuate drug seeking, and the neuronal subtype specificity of this effect, is unclear. Methods: The present study examined the effect of DBS in the nucleus accumbens on neuronal plasticity and cocaine-primed reinstatement of cocaine seeking behavior in rats. Results: Electrical DBS of the accumbens shell attenuated cocaine primed reinstatement across a range of frequencies in male rats, including as low as 12 Hz. The majority of nucleus accumbens neurons are medium spiny neurons (MSNs), which can be differentiated in terms of projections and effects on cocaine-related behaviors by expression of dopamine D1 receptors (D1DRs) or D2DRs. In slice electrophysiology experiments, 12 Hz electrical stimulation evoked long term potentiation (LTP) in eYFP labeled D1DR-MSNs and D2DR-MSNs from cocaine naive male and female rats. However, in rats that self-administered cocaine and underwent extinction training, a paradigm identical to our reinstatement experiments, electrical DBS only elicited LTP in D2DR-MSNs from male rats; this effect was replicated by optical stimulation in rats expressing Cre-dependent ChR2 in D2DR-MSNs. Low-frequency optogenetic-DBS in D1DR-containing or D2DR-containing neurons attenuated cocaine-primed reinstatement of cocaine seeking in male but not female rats. Conclusions: These results suggest that administering DBS in the nucleus accumbens shell at lower frequencies effectively, but sex-specifically, suppresses cocaine craving, perhaps in part by reversing synaptic plasticity deficits selectively in D2DR-MSNs.

High frequency DBS-like optogenetic stimulation of nucleus accumbens dopamine D2 receptor-containing neurons attenuates cocaine reinstatement in male rats.

Previous work indicated that deep brain stimulation (DBS) of the nucleus accumbens shell in male rats attenuated reinstatement of cocaine seeking, an animal model of craving. However, the potential differential impact of DBS on specific populations of neurons to drive the suppression of cocaine seeking is unknown. Medium spiny neurons in the nucleus accumbens are differentiated by expression of dopamine D1 receptors (D1DRs) or D2DRs, activation of which promotes or inhibits cocaine-related behaviors, respectively. The advent of transgenic rat lines expressing Cre recombinase selectively in D1DR-containing or D2DR-containing neurons, when coupled with Cre-dependent virally mediated gene transfer of channelrhodopsin (ChR2), enabled mimicry of DBS in a selective subpopulation of neurons during complex tasks. We tested the hypothesis that high frequency DBS-like optogenetic stimulation of D1DR-containing neurons in the accumbens shell would potentiate, whereas stimulation of D2DR-containing neurons in the accumbens shell would attenuate, cocaine-primed reinstatement of cocaine seeking. Results indicated that high frequency, DBS-like optogenetic stimulation of D2DR-containing neurons attenuated reinstatement of cocaine seeking in male rats, whereas DBS-like stimulation of D1DR-containing neurons did not alter cocaine-primed reinstatement. Surprisingly, DBS-like optogenetic stimulation did not alter reinstatement of cocaine seeking in female rats. In rats which only expressed eYFP, intra-accumbens optogenetic stimulation did not alter cocaine reinstatement, indicating that the effect of DBS-like stimulation to attenuate cocaine reinstatement is mediated specifically by ChR2 rather than by prolonged light delivery. These results suggest that DBS of the accumbens may attenuate cocaine-primed reinstatement in male rats through the selective manipulation of D2DR-containing neurons.

Low frequency deep brain stimulation of nucleus accumbens shell neuronal subpopulations attenuates cocaine seeking selectively in male rats.

The present study examined the effect of deep brain stimulation (DBS) in the nucleus accumbens shell on cocaine seeking and neuronal plasticity in rats. Electrical DBS of the accumbens shell attenuated cocaine primed reinstatement across a range of frequencies as low as 12 Hz in male rats. Nucleus accumbens medium spiny neurons (MSNs) can be differentiated by expression of dopamine D1 receptors (D1DRs) or D2DRs. Low-frequency optogenetic-DBS in D1DR- or D2DR-containing neurons attenuated cocaine seeking in male but not female rats. In slice electrophysiology experiments, 12 Hz electrical stimulation evoked long term potentiation (LTP) in D1DR-MSNs and D2DR-MSNs from cocaine naive male and female rats. However, in cocaine-experienced rats, electrical and optical DBS only elicited LTP in D2DR-MSNs from male rats. These results suggest that low frequency DBS in the nucleus accumbens shell effectively, but sex-specifically, suppresses cocaine seeking, which may be associated with the reversal of synaptic plasticity deficits in D2DR-MSNs.

Surgical Techniques for the Repair of Webbed Neck: A Scoping Review.

Webbed neck is a rare condition characterized by bilateral subcutaneous bands, which extend from approximately the mastoid to the acromion. Given its rarity, the literature lacks a review of the techniques used in the repair of this condition. We performed a scoping review to define and summarize the surgical techniques been used in the treatment of webbed neck, with the goal of better equipping the surgeons' armamentarium. Two databases, PubMed and Scopus, were searched from inception through December 27, 2021. Studies were considered for inclusion if they (1) described the webbed neck condition and (2) reported results of surgical correction of this condition. Surgical outcomes and follow-up durations were reported as available. Twenty-two manuscripts were analyzed and included data on 60 patients. The most common syndrome associated with webbed neck was Turner syndrome (48 patients). The most frequently documented procedure technique was a Z-Plasty (38 patients). Other procedures described included: butterfly correction, V-Y Plasty, posterior cervical lift, skin excision, tissue expansion plus skin excision, T to M rearrangement, and subcutaneous fascial excision. Documented complications included hypertrophy of procedure scars or webbed neck recurrence. In summary, we present the first full literature review of the surgical techniques used in the repair of webbed neck. When selecting the technique for repair of the webbed neck, function and cosmesis are important considerations. Future studies should collect standardized outcomes data to appropriately assess and compare the described procedures.

Recreational Motorized Vehicle Use Under the Influence of Alcohol or Drugs Significantly Increases Odds of Craniofacial Injury.

Study Design: Cross-sectional study. Objective: Concurrent substance-use, including alcohol and drugs, increases the risks of many recreational activities. Our purpose was to determine the relationship between substance use and craniofacial injuries in a large population of patients experiencing trauma due to recreational motorized vehicle use. Methods: We report a cross-sectional study of patients reported to the National Electronic Injury Surveillance System (NEISS) from January 1, 2019 to December 31, 2019, in the United States. Patients were included in our study if they were evaluated in the emergency department (ED) for a recreational motorized vehicle-related injury. Primary outcome was craniofacial injury. Results: There were a total of 6,485 adult patients who experience an injury after recreational motorized vehicle trauma reported by NEISS-participating EDs during the study period. Of this, 1,416 (21.8%) patients had a craniofacial injury, and 201 patients with craniofacial injuries were under the influence of alcohol/drugs (201/1,416; 14.2%). Injured patients under the influence of alcohol/drugs experienced greater odds of sustaining a general craniofacial injury (OR 2.50, 95% CI: 2.07-3.01, P < .0001), including craniofacial fracture (OR: 2.98, 95% CI: 2.01-4.40, P < .0001), laceration (OR: 2.19, 95% CI: 1.51-3.16, P < .00001) and internal injury (OR: 2.33, 95% CI: 1.84-2.95, P < .00001) than injured patients not under the influence. Conclusions: Using recreational motorized vehicles under the influence of alcohol or drugs is not safe and increases the likelihood of craniofacial injuries, including fractures, lacerations, and internal injuries. As operating these recreational motorized vehicles under the influence is illegal, the law should be strictly enforced to prevent the occurrence of these injuries. Additional undertakings to increase helmet usage would be valuable.