Function and biochemistry of the dorsolateral prefrontal cortex during placebo analgesia: how the certainty of prior experiences shapes endogenous pain relief.

Prior experiences, conditioning cues, and expectations of improvement are essential for placebo analgesia expression. The dorsolateral prefrontal cortex is considered a key region for converting these factors into placebo responses. Since dorsolateral prefrontal cortex neuromodulation can attenuate or amplify placebo, we sought to investigate dorsolateral prefrontal cortex biochemistry and function in 38 healthy individuals during placebo analgesia. After conditioning participants to expect pain relief from a placebo "lidocaine" cream, we collected baseline magnetic resonance spectroscopy (1H-MRS) at 7 Tesla over the right dorsolateral prefrontal cortex. Following this, functional magnetic resonance imaging scans were collected during which identical noxious heat stimuli were delivered to the control and placebo-treated forearm sites. There was no significant difference in the concentration of gamma-aminobutyric acid, glutamate, Myo-inositol, or N-acetylaspartate at the level of the right dorsolateral prefrontal cortex between placebo responders and nonresponders. However, we identified a significant inverse relationship between the excitatory neurotransmitter glutamate and pain rating variability during conditioning. Moreover, we found placebo-related activation within the right dorsolateral prefrontal cortex and altered functional magnetic resonance imaging coupling between the dorsolateral prefrontal cortex and the midbrain periaqueductal gray, which also correlated with dorsolateral prefrontal cortex glutamate. These data suggest that the dorsolateral prefrontal cortex formulates stimulus-response relationships during conditioning, which are then translated to altered cortico-brainstem functional relationships and placebo analgesia expression.

Does Prednisone Dose Affect Rates of Periprosthetic Joint Infection Following Primary Total Hip and Total Knee Arthroplasty?

BACKGROUND: Prednisone use is associated with higher rates of periprosthetic joint infection (PJI) following total joint arthroplasty (TJA). However, the relationship between prednisone dosage and infection risk is ill-defined. Therefore, this study aimed to assess the relationship between prednisone dosage and rates of PJI following TJA. METHODS: A national database was queried for all elective total hip (THA) and total knee arthroplasty (TKA) patients between 2015 and 2020. Patients who received oral prednisone following TJA were matched in a 1:2 ratio based on age and sex to patients who did not. Univariate and multivariate regression analyses were performed to assess the 90-day risk of infectious complications based on prednisone dosage as follows: 0 to 5, 6 to 10, 11 to 20, 21 to 30, and >30 milligrams. Overall, 1,322,043 patients underwent elective TJA (35.9% THA, 64.1% TKA). Of these, 14,585 (1.1%) received prednisone and were matched to 29,170 patients who did not. RESULTS: After controlling for confounders, TKA patients taking prednisone were at increased risk for sepsis (adjusted odds ratio [aOR] 2.76, P < .001), PJI (aOR 2.67, P < .001), and surgical site infection (aOR: 2.56, P = .035). THA patients taking prednisone were at increased risk for sepsis (aOR: 3.21, P < .001) and PJI (aOR: 1.73, P = .001). No dose-dependent relationship between prednisone and infectious complications was identified when TJA was assessed in aggregate. CONCLUSION: Patients receiving prednisone following TJA were at increased risk of PJI and sepsis. A dose-dependent relationship between prednisone and infectious complications was not identified. Arthroplasty surgeons should be aware of these risks and counsel TJA patients who receive prednisone therapy.

Safety and Efficacy of Rivaroxaban in Primary Total Hip and Knee Arthroplasty.

BACKGROUND: An optimal venous thromboembolism prophylaxis agent should balance efficacy and safety. While rivaroxaban provides effective venous thromboembolism prophylaxis after total joint arthroplasty, it may be associated with higher rates of bleeding. This study aimed to compare the safety and efficacy of rivaroxaban to aspirin and enoxaparin. METHODS: A large national database was queried for patients who underwent elective primary total hip (THA) or total knee arthroplasty (TKA) from January 2015 through December 2020 who received rivaroxaban, aspirin, or enoxaparin. Multivariate analyses were performed to assess the 90-day risk of bleeding and thromboembolic complications. Among TKA patients identified, 86,721 (10.8%) received rivaroxaban, 408,038 (50.8%) received aspirin, and 108,377 (13.5%) received enoxaparin. Among THA patients, 42,469 (9.5%) received rivaroxaban, 242,876 (54.5%) received aspirin, and 59,727 (13.4%) received enoxaparin. RESULTS: After accounting for confounding factors, rivaroxaban was associated with increased risk of transfusion (TKA: adjusted odds ratio [aOR] = 2.58, P < .001; THA: aOR 1.64, P < .001), pulmonary embolism (TKA: aOR = 1.25, P = .007), and deep vein thrombosis (TKA: aOR = 1.13, P = .022) compared to aspirin. Compared to enoxaparin, rivaroxaban was associated with an increased risk of combined bleeding events (TKA: aOR = 1.07, P < .001, THA: aOR = 1.11, P < .001), but decreased risk of combined prothrombotic events (THA: aOR = 0.85, P = .036). CONCLUSION: Rivaroxaban chemoprophylaxis following TKA and THA was associated with an increased risk of bleeding and prothrombotic complications compared to aspirin and enoxaparin.

Is Intraoperative Dexamethasone Utilization Associated With Increased Rates of Periprosthetic Joint Infection Following Total Joint Arthroplasty?

BACKGROUND: Intraoperative dexamethasone can reduce postoperative pain and nausea following total knee (TKA) and total hip arthroplasty (THA). To the best of our knowledge, no study to date has been adequately powered to detect the risk of periprosthetic joint infection (PJI) from early dexamethasone exposure. This study aimed to assess PJI rates and complications in patients undergoing primary elective TKA and THA who received intraoperative dexamethasone. METHODS: A national database was used to identify adults undergoing primary elective TKA and THA between 2015 and 2020. Patients who received intraoperative dexamethasone and those who did not were identified. The primary endpoint was 90-day risk of infectious complications. Secondary end points included thromboembolic, pulmonary, renal, and wound complications. Multivariate analyses were performed to assess the risk of all endpoints between cohorts. Between 2015 and 2020, 1,322,025 patients underwent primary elective TJA, of which 857,496 (64.1%) underwent TKA and 474,707 (35.9%) underwent TKA. RESULTS: In patients who underwent TKA, dexamethasone was associated with lower risk of PJI (adjusted odds ratio: 0.87, 95% CI: 0.82-0.93, P < .001) as well as other secondary endpoints such as pulmonary embolism, deep vein thrombosis, and acute kidney injury. In patients who underwent THA, dexamethasone was associated with a lower risk of PJI (adjusted odds ratio: 0.80, 95% CI: 0.73-0.86, P < .001) as well as other secondary endpoints such as pulmonary embolism, deep vein thrombosis, acute kidney injury, and pneumonia. CONCLUSION: Intraoperative dexamethasone was not associated with increased risk of infectious complications. The data presented here provide evidence in support of intraoperative dexamethasone utilization during primary TKA or THA.

Neck Muscle Coactivation Response to Varied Levels of Mental Workload During Simulated Flight Tasks.

OBJECTIVE: To evaluate neck muscle coactivation across different levels of mental workload during simulated flight tasks. BACKGROUND: Neck pain (NP) is highly prevalent among military aviators. Given the complex nature within the flight environment, mental workload may be a risk factor for NP. This may induce higher levels of neck muscle coactivity, which over time may accelerate fatigue, increase neck discomfort, and affect flight task performance. METHOD: Three counterbalanced mental workload conditions represented by simulated flight tasks modulated by interstimulus frequency and complexity were investigated using the Modifiable Multitasking Environment (ModME). The primary measure was a neck coactivation index to describe the neuromuscular effort of the neck muscles as a system. Additional measures included perceived workload (NASA TLX), subjective discomfort, and task performance. Participants (n = 60; 30M, 30F) performed three test conditions over 1 hr each while seated in a simulated seating environment. RESULTS: Neck coactivation indices (CoA) and subjective neck discomfort corresponded with increasing level of mental workload. Average CoAs for low, medium, and high workloads were: .0278(SD = .0232), .0286(SD = .0231), and .0295(SD = .0228), respectively. NASA TLX mental, temporal, effort, and overall scores also increased with the level of mental workload assigned. For ModME task performance, the overall performance score, monitoring accuracy, and resource management accuracy decreased while reaction times increased with the increasing level of mental workload. Communication accuracy was lowest with the low mental workload but had higher reaction times relative to increasing workload. CONCLUSION: Mental workload affects neck muscle coactivation during combinations of simulated flight tasks within a simulated helicopter seating environment. APPLICATION: The results of this study provide insights into the physical response to mental workload. With increasing multisensory modalities within the work environment, these insights may assist the consideration of physical effects from cognitive factors.

Exploring the Interaction Between Head-Supported Mass, Posture, and Visual Stress on Neck Muscle Activation.

OBJECTIVE: Assess neck muscle activity for varying interactions between helmet, posture, and visual stress in a simulated "helo-hunch" posture. BACKGROUND: Military aviators frequently report neck pain (NP). Risk factors for NP include head-supported mass, awkward postures, and mental workload. Interactions between these factors could induce constant low-level muscle activation during helicopter flight and better explain instances of NP. METHOD: Interactions between physical loading (helmet doffed/donned), posture (symmetric/asymmetric), and visual stress (low/high contrast) were studied through neck muscle electromyography (EMG), head kinematics, subjective discomfort, perceived workload, and task performance. Subjects (n = 16) performed eight 30-min test conditions (varied physical loading, posture, and visual stress) while performing a simple task in a simulated "helo-hunch" seating environment. RESULTS: Conditions with a helmet donned had fewer EMG median frequency cycles (which infer motor unit rotation for rest/recovery, where more cycles are better) in the left cervical extensor and left sternocleidomastoid. Asymmetric posture (to the right) resulted in higher normalized EMG activity in the right cervical extensor and left sternocleidomastoid and resulted in less lateral bending compared with neutral across all conditions. Conditions with high visual stress also resulted in fewer EMG cycles in the right cervical extensor. CONCLUSION: A complex interaction exists between the physical load of the helmet, postural stress from awkward postures, and visual stress within a simulated "helo-hunch" seating environment. APPLICATION: These results provide insight into how visual factors influence biomechanical loading. Such insights may assist future studies in designing short-term administrative controls and long-term engineering controls.

Brainstem Mechanisms of Pain Modulation: A within-Subjects 7T fMRI Study of Placebo Analgesic and Nocebo Hyperalgesic Responses.

Pain perception can be powerfully influenced by an individual's expectations and beliefs. Although the cortical circuitry responsible for pain modulation has been thoroughly investigated, the brainstem pathways involved in the modulatory phenomena of placebo analgesia and nocebo hyperalgesia remain to be directly addressed. This study used ultra-high-field 7 tesla functional MRI (fMRI) to accurately resolve differences in brainstem circuitry present during the generation of placebo analgesia and nocebo hyperalgesia in healthy human participants (N = 25, 12 male). Over 2 successive days, through blinded application of altered thermal stimuli, participants were deceptively conditioned to believe that two inert creams labeled lidocaine (placebo) and capsaicin (nocebo) were acting to modulate their pain relative to a third Vaseline (control) cream. In a subsequent test phase, fMRI image sets were collected while participants were given identical noxious stimuli to all three cream sites. Pain intensity ratings were collected and placebo and nocebo responses determined. Brainstem-specific fMRI analysis revealed altered activity in key pain modulatory nuclei, including a disparate recruitment of the periaqueductal gray (PAG)-rostral ventromedial medulla (RVM) pathway when both greater placebo and nocebo effects were observed. Additionally, we found that placebo and nocebo responses differentially activated the parabrachial nucleus but overlapped in engagement of the substantia nigra and locus coeruleus. These data reveal that placebo and nocebo effects are generated through differential engagement of the PAG-RVM pathway, which in concert with other brainstem sites likely influences the experience of pain by modulating activity at the level of the dorsal horn.SIGNIFICANCE STATEMENT Understanding endogenous pain modulatory mechanisms would support development of effective clinical treatment strategies for both acute and chronic pain. Specific brainstem nuclei have long been known to play a central role in nociceptive modulation; however, because of the small size and complex organization of the nuclei, previous neuroimaging efforts have been limited in directly identifying how these subcortical networks interact during the development of antinociceptive and pro-nociceptive effects. We used ultra-high-field fMRI to resolve brainstem structures and measure signal change during placebo analgesia and nocebo hyperalgesia. We define overlapping and disparate brainstem circuitry responsible for altering pain perception. These findings extend our understanding of the detailed organization and function of discrete brainstem nuclei involved in pain processing and modulation.

Applying switchable Cas9 variants to in vivo gene editing for therapeutic applications.

Progress in targeted gene editing by programmable endonucleases has paved the way for their use in gene therapy. Particularly, Cas9 is an endonuclease with high activity and flexibility, rendering it an attractive option for therapeutic applications in clinical settings. Many disease-causing mutations could potentially be corrected by this versatile new technology. In addition, recently developed switchable Cas9 variants, whose activity can be controlled by an external stimulus, provide an extra level of spatiotemporal control on gene editing and are particularly desirable for certain applications. Here, we discuss the considerations and difficulties for implementing Cas9 to in vivo gene therapy. We put particular emphasis on how switchable Cas9 variants may resolve some of these barriers and advance gene therapy in the clinical setting.

A survey exploring ophthalmologists' attitudes and beliefs in performing Immediately Sequential Bilateral Cataract Surgery in the United Kingdom.

BACKGROUND: The standard approach to treat cataracts is Delayed Sequential Bilateral Cataract Surgery (DSBCS), during which patients have a separate operation date for each eye. An alternative method of delivery is Immediately Sequential Bilateral Cataract Surgery (ISBCS). The aim of this project was to examine the attitudes and beliefs of UK ophthalmologists towards ISBCS, explore their reasons to either practise or not practise ISBCS and identify barriers hindering its implementation in the UK. METHODS: A questionnaire was distributed to consultant members of The Royal College of Ophthalmologists (RCOphth, UK) and collected electronically. An initial screening question in regards to prior experience with ISBCS directed the rest of the survey; participants were asked to rate the importance of several factors with regards to performing ISBCS. Free text options were also available. Descriptive analysis was subsequently performed. RESULTS: Of the 1357 recipients, 130 (9.6%) ophthalmologists completed the survey. Of those, 13.9% were currently performing ISBCS, 83.1% had never performed, and 3.1% had previously done so but since stopped. The main factors that acted as barriers were lack of: (1) College approval (20.5%); (2) medico-legal approval (20.2%); (3) evidence to support the use of ISBCS (16.0%); and (4) hospital approval (13.3%). Additionally, the perceived risk of complications for patients played an important role when considering ISBCS, with the risk of endophthalmitis being most feared. CONCLUSIONS: This survey demonstrates some of the barriers that prevent ophthalmologist's performing ISBCS in the UK. There is a need for further exploration in this field to evaluate the effect of addressing any of these concerns on the implementation of ISBCS.

Public Perceptions of Cross-Sex Vascularized Composite Allotransplantation.

BACKGROUND: Cross-sex vascularized composite allotransplantation has been performed in cadaveric facial transplantation and clinical extremity transplantation. Understanding the challenge of appropriate donor-recipient matching, this study sought to characterize the public's perception of cross-sex vascularized composite allotransplantation. METHODS: Participants were surveyed in New York City. Data collected included demographics and willingness to donate vascularized composite allografts (VCAs) of various types. Similar questions were asked in the context of same-sex and cross-sex donation. RESULTS: A total of 101 participants (male: 56.4%; age ≤35 years: 62.4%) were surveyed. The majority expressed willingness to donate to recipients of a different sex (hand: 78.2%, face: 56.4%, penis or uterus: 69.3%, lower limb: 81.2%, abdominal wall: 80.2%, larynx: 81.2%, and solid organs: 85.2%). Among VCAs, willingness to donate facial allografts was significantly different in same-sex versus cross-sex contexts (64.4% vs 56.4%; P = 0.008). Participants were also significantly more likely to donate VCAs to same-sex recipients on behalf of themselves versus loved ones (P < 0.05). There was significantly lower willingness to receive cross-sex versus same-sex facial (P = 0.022) and genital allografts (P = 0.022). Education on the preservation of recipient masculinity or femininity in cross-sex facial transplantation increased participants' willingness to receive a cross-sex face transplant from 56.4% to 71.3% (P = 0.001). CONCLUSIONS: This study highlights the urban public's acceptance of VCA donation or reception regardless of sex mismatch. There is increased willingness to receive a cross-sex face transplant after education, highlighting opportunities for future focused interventions to increase public awareness and ultimately the donor pool.

Have We Achieved Optimal Skin Color Matching in Partial Facial Transplantation? A Survey Study of the General Public and Medical Professionals.

BACKGROUND: Skin color matching is an essential factor in achieving optimal aesthetic outcome in partial facial transplantation. However, there is no published literature evaluating the success of color matching to date. Furthermore, a medical professional's perception of an optimal color match may not necessarily translate to that of the general public. The purpose of our study was to evaluate skin color matching between the donor allograft and recipient native tissue in partial facial transplantations to determine the level of success perceived by the general public and medical professionals. METHODS: Published photographs of partial face transplant recipients were used to create a survey where recipient native and donor allograft skin samples were juxtaposed. Thirty-three members of the general public and 30 medical professionals were asked to rate skin color match on a scale from "excellent match" to "not a match." RESULTS: Overall, 47% of given ratings were positive, indicating an "excellent" or "good match," and 53% of ratings were negative, indicating a "poor match" or "lack of match" between the skin sample pairings shown. Of the 19 partial face transplant patients who were rated, 9 patients received >50% positive ratings, and 10 patients received <50% positive ratings. Medical professionals consistently gave more positive ratings, with statistically significant differences in 7 of the 19 rated patients (P < 0.05). CONCLUSION: The results suggest that there is need for improvement in color matching in partial facial transplantation, and that the general public is more critical of skin color matching compared to medical professionals.

Telemedicine and the COVID-19 Pandemic: Are We Ready to Go Live?

Telemedicine use in the field of wound care had been increasing in popularity when the novel coronavirus 2019 paralyzed the globe in early 2020. To combat the constraints of healthcare delivery during this time, the use of telemedicine has been further expanded. Although many limitations of telemedicine are still being untangled, the benefits of virtual care are being realized in both inpatient and outpatient settings. In this article, the advantages and disadvantages of telemedicine are discussed through two case examples that highlight the promise of implementation during and beyond the pandemic.

Changes in Brainstem Pain Modulation Circuitry Function over the Migraine Cycle.

The neural mechanism responsible for migraine remains unclear. While an external trigger has been proposed to initiate a migraine, it has also been proposed that changes in brainstem function are critical for migraine headache initiation and maintenance. Although the idea of altered brainstem function has some indirect support, no study has directly measured brainstem pain modulation circuitry function in migraineurs particularly immediately before a migraine. In male and female humans, we performed fMRI in 31 controls and 31 migraineurs at various times in their migraine cycle. We measured brainstem function during noxious orofacial stimulation and assessed resting-state functional connectivity. First, we found that, in individual migraineurs, pain sensitivity increased over the interictal period but then dramatically decreased immediately before a migraine. Second, despite overall similar pain intensity ratings between groups, in the period immediately before a migraine, compared with controls and other migraine phases, migraineurs displayed greater activation in the spinal trigeminal nucleus during noxious orofacial stimulation and reduced functional connectivity of this region with the rostral ventromedial medulla. Additionally, during the interictal phase, migraineurs displayed reduced activation of the midbrain periaqueductal gray matter and enhanced periaqueductal gray connectivity with the rostral ventromedial medulla. These data support the hypothesis that brainstem sensitivity fluctuates throughout the migraine cycle. However, in contrast to the prevailing hypothesis, our data suggest that, immediately before a migraine attack, endogenous analgesic mechanisms are enhanced and incoming noxious inputs are less likely to reach higher brain centers.SIGNIFICANCE STATEMENT It has been hypothesized that alterations in brainstem function are critical for the generation of migraine. In particular, modulation of orofacial pain pathways by brainstem circuits alters the propensity of external triggers or ongoing spontaneous activity to evoke a migraine attack. We sought to obtain empirical evidence to support this theory. Contrary to our hypothesis, we found that pain sensitivity decreased immediately before a migraine, and this was coupled with increased sensitivity of the spinal trigeminal nucleus to noxious stimuli. We also found that resting connectivity within endogenous pain modulation circuitry alters across the migraine cycle. These changes may reflect enhanced and diminished neural tone states proposed to be critical for the generation of a migraine and underlie cyclic fluctuations in migraine brainstem sensitivity.

Brainstem Pain-Control Circuitry Connectivity in Chronic Neuropathic Pain.

Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human psychophysical studies show that patients with chronic pain display altered pain-modulation efficacy, it remains unknown whether brainstem pain-modulation circuits are altered in individuals with chronic pain. The aim of the present investigation was to determine whether, in humans, chronic pain following nerve injury is associated with altered ongoing functioning of the brainstem descending modulation systems. Using resting-state functional magnetic resonance imaging, we found that male and female patients with chronic neuropathic orofacial pain show increased functional connectivity between the rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions, including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC). We also identified an increase in RVM functional connectivity with the region that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In addition, the vlPAG and LC displayed increased functional connectivity strengths with higher brain regions, including the hippocampus, nucleus accumbens, and anterior cingulate cortex, in individuals with chronic pain. These data reveal that chronic pain is associated with altered ongoing functioning within the endogenous pain-modulation network. These changes may underlie enhanced descending facilitation of processing at the primary synapse, resulting in increased nociceptive transmission to higher brain centers. Further, our findings show that higher brain regions interact with the brainstem modulation system differently in chronic pain, possibly reflecting top-down engagement of the circuitry alongside altered reward processing in pain conditions.SIGNIFICANCE STATEMENT Experimental animal models and human psychophysical studies suggest that altered functioning of brainstem pain-modulation systems contributes to the maintenance of chronic pain. However, the function of this circuitry has not yet been explored in humans with chronic pain. In this study, we report that individuals with orofacial neuropathic pain show altered functional connectivity between regions within the brainstem pain-modulation network. We suggest that these changes reflect largely central mechanisms that feed back onto the primary nociceptive synapse and enhance the transfer of noxious information to higher brain regions, thus contributing to the constant perception of pain. Identifying the mechanisms responsible for the maintenance of neuropathic pain is imperative for the development of more efficacious therapies.

Ecological consequences of forest elephant declines for Afrotropical forests.

Poaching is rapidly extirpating African forest elephants (Loxodonta cyclotis) from most of their historical range, leaving vast areas of elephant-free tropical forest. Elephants are ecological engineers that create and maintain forest habitat; thus, their loss will have large consequences for the composition and structure of Afrotropical forests. Through a comprehensive literature review, we evaluated the roles of forest elephants in seed dispersal, nutrient recycling, and herbivory and physical damage to predict the cascading ecological effects of their population declines. Loss of seed dispersal by elephants will favor tree species dispersed abiotically and by smaller dispersal agents, and tree species composition will depend on the downstream effects of changes in elephant nutrient cycling and browsing. Loss of trampling and herbivory of seedlings and saplings will result in high tree density with release from browsing pressures. Diminished seed dispersal by elephants and high stem density are likely to reduce the recruitment of large trees and thus increase homogeneity of forest structure and decrease carbon stocks. The loss of ecological services by forest elephants likely means Central African forests will be more like Neotropical forests, from which megafauna were extirpated thousands of years ago. Without intervention, as much as 96% of Central African forests will have modified species composition and structure as elephants are compressed into remaining protected areas. Stopping elephant poaching is an urgent first step to mitigating these effects, but long-term conservation will require land-use planning that incorporates elephant habitat into forested landscapes that are being rapidly transformed by industrial agriculture and logging.

The Risk of Acute Infection Following Intra-articular Corticosteroid Injection Into a Pre-existing Total Knee Arthroplasty.

BACKGROUND: No previous studies have investigated the risk of infection following intra-articular corticosteroid injection (IACI) into a pre-existing total knee arthroplasty (TKA). The aim of this study is to determine the risk of acute infection following IACI into a pre-existing TKA. METHODS: A retrospective chart review identified all patients at a single institution between October 2009 and May 2015 that had an ipsilateral knee injection subsequent to a TKA. The risk of acute infection, as defined by development of an infection within 3 months of IACI, was determined via review of clinic notes, operative reports, laboratory records, and telephone interviews. RESULTS: A total of 1845 injections in 736 patients met the inclusion criteria. In total, 101 (4.8%) patients were lost to follow-up. Three infections in 3 patients occurred within 3 months of IACI, yielding an infection rate of 0.16% per injection, or 1 infection in every 625 IACIs following TKA. CONCLUSION: This study is the first to investigate the risk of acute infection following injection of corticosteroid into a pre-existing TKA. Given the dire consequences of infection following TKA, the routine use of IACI into a pre-existing TKA should be avoided, and a thorough workup should be performed in any patient with a painful TKA prior to consideration of IACI.

The effects of gestational stress and Selective Serotonin reuptake inhibitor antidepressant treatment on structural plasticity in the postpartum brain--A translational model for postpartum depression.

This article is part of a Special Issue "Parental Care". Postpartum depression (PPD) is a common complication following childbirth experienced by one in every five new mothers. Although the neural basis of PPD remains unknown, previous research in rats has shown that gestational stress, a risk factor for PPD, induces depressive-like behavior during the postpartum period. Moreover, the effect of gestational stress on postpartum mood is accompanied by structural modifications within the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC)-limbic regions that have been linked to PPD. Mothers diagnosed with PPD are often prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant medications and yet little is known about their effects in models of PPD. Thus, here we investigated whether postpartum administration of Citalopram, an SSRI commonly used to treat PPD, would ameliorate the behavioral and morphological consequences of gestational stress. In addition, we examined the effects of gestational stress and postpartum administration of Citalopram on structural plasticity within the basolateral amygdala (BLA) which together with the mPFC and NAc forms a circuit that is sensitive to stress and is involved in mood regulation. Our results show that postpartum rats treated with Citalopram do not exhibit gestational stress-induced depressive-like behavior in the forced swim test. In addition, Citalopram was effective in reversing gestational stress-induced structural alterations in the postpartum NAc shell and mPFC. We also found that gestational stress increased spine density within the postpartum BLA, an effect which was not reversed by Citalopram treatment. Overall, these data highlight the usefulness of gestational stress as a valid and informative translational model for PPD. Furthermore, they suggest that structural alterations in the mPFC-NAc pathway may underlie stress-induced depressive-like behavior during the postpartum period and provide much needed information on how SSRIs may act in the maternal brain to treat PPD.

Functional Outcomes After Operative Treatment of Calcaneal Fractures: Midterm Review.

The purpose of this article is to report midterm follow-up of operatively treated calcaneus fractures. All patients with a calcaneus fracture, treated with open reduction and internal fixation (ORIF) using the extensile lateral approach, were identified. Functional outcomes were assessed using the American Orthopaedic Foot and Ankle Society's (AOFAS) ankle-hindfoot assessment, SF-36, and a questionnaire. There were 20 patients (25 fractures): 16 males and four females. The average age was 42 years (range, 16-73 years) and the mean follow-up time was 40 months (range, 13-73 months). The mean AOFAS score was 67.8 (SD = 19.3) and the mean SF-36 score was 55.7 (SD = 26.3). Patients in an motor vehicle accident had more associated injuries. Statistically significantly worse AOFAS scores were noted in patients with ORIF > 21 days after their injury (p = .047). Many lifestyle alterations were found to be present, including change in work, participation in recreational activities, footwear, and use of ambulatory assistive devices.

Rapid temporal recalibration is unique to audiovisual stimuli.

Following prolonged exposure to asynchronous multisensory signals, the brain adapts to reduce the perceived asynchrony. Here, in three separate experiments, participants performed a synchrony judgment task on audiovisual, audiotactile or visuotactile stimuli and we used inter-trial analyses to examine whether temporal recalibration occurs rapidly on the basis of a single asynchronous trial. Even though all combinations used the same subjects, task and design, temporal recalibration occurred for audiovisual stimuli (i.e., the point of subjective simultaneity depended on the preceding trial's modality order), but none occurred when the same auditory or visual event was combined with a tactile event. Contrary to findings from prolonged adaptation studies showing recalibration for all three combinations, we show that rapid, inter-trial recalibration is unique to audiovisual stimuli. We conclude that recalibration occurs at two different timescales for audiovisual stimuli (fast and slow), but only on a slow timescale for audiotactile and visuotactile stimuli.

Oronasopharyngeal suction versus wiping of the mouth and nose at birth: a randomised equivalency trial.

BACKGROUND: Wiping of the mouth and nose at birth is an alternative method to oronasopharyngeal suction in delivery-room management of neonates, but whether these methods have equivalent effectiveness is unclear. METHODS: For this randomised equivalency trial, neonates delivered at 35 weeks' gestation or later at the University of Alabama at Birmingham Hospital, Birmingham, AL, USA, between October, 2010, and November, 2011, were eligible. Before birth, neonates were randomly assigned gentle wiping of the face, mouth (implemented by the paediatric or obstetric resident), and nose with a towel (wipe group) or suction with a bulb syringe of the mouth and nostrils (suction group). The primary outcome was the respiratory rate in the first 24 h after birth. We hypothesised that respiratory rates would differ by fewer than 4 breaths per min between groups. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01197807. FINDINGS: 506 neonates born at a median of 39 weeks' gestation (IQR 38-40) were randomised. Three parents withdrew consent and 15 non-vigorous neonates with meconium-stained amniotic fluid were excluded. Among the 488 treated neonates, the mean respiratory rates in the first 24 h were 51 (SD 8) breaths per min in the wipe group and 50 (6) breaths per min in the suction group (difference of means 1 breath per min, 95% CI -2 to 0, p<0·001). INTERPRETATION: Wiping the nose and mouth has equivalent efficacy to routine use of oronasopharyngeal suction in neonates born at or beyond 35 weeks' gestation. FUNDING: None.