Ticks without borders: Microbial communities of immature Neotropical tick species parasitizing migratory landbirds along northern Gulf of Mexico.

The long-distance, seasonal migrations of birds make them an effective ecological bridge for the movement of ticks. The introduction of exotic tick species to new geographical regions can lead to the emergence of novel tick-borne pathogens or the re-emergence of previously eradicated ones. This study assessed the prevalence of exotic tick species parasitizing resident, short-distance, and long-distance songbirds during spring and autumn at stopover sites in the northern Gulf of Mexico using the mitochondrial 12S rDNA gene. Birds were captured for tick collection from six different sites from late August to early November in both 2018 and 2019. The highest number of ticks were collected in the 2019 season. Most ticks were collected off the Yellow-breasted Chat (Icteria virens) and Common Yellowthroat (Geothlypis trichas), and 54% of the total ticks collected were from Grand Chenier, LA. A high throughput 16S ribosomal RNA sequencing approach was followed to characterize the microbial communities and identify pathogenic microbes in all tick samples. Tick microbial communities, diversity, and community structure were determined using quantitative insight into microbial ecology (QIIME). The sparse correlations for compositional data (SparCC) approach was then used to construct microbial network maps and infer microbial correlations. A total of 421 individual ticks in the genera Amblyomma, Haemaphysalis, and Ixodes were recorded from 28 songbird species, of which Amblyomma and Amblyomma longirostre was the most abundant tick genus and species, respectively. Microbial profiles showed that Proteobacteria was the most abundant phylum. The most abundant bacteria include the pathogenic Rickettsia and endosymbiont Francisella, Candidatus Midichloria, and Spiroplasma. BLAST analysis and phylogenetic reconstruction of the Rickettsia sequences revealed the highest similarities to pathogenic spotted and non-spotted fever groups, including R. buchneri, R. conorii, R. prowazekii, R. bellii, R. australis, R. parkeri, R. monacensis, and R. monteiroi. Permutation multivariate analysis of variance revealed that the relative abundance of Francisella and Rickettsia drives microbial patterns across the tick genera. We also observed a higher percentage of positive correlations in microbe-microbe interactions among members of the microbial communities. Network analysis suggested a negative correlation between a) Francisella and Rickettsia and, b) Francisella and Cutibacterium. Lastly, mapping the distributions of bird species parasitized during spring migrations highlighted geographic hotspots where migratory songbirds could disperse ticks and their pathogens at stopover sites or upon arrival to their breeding grounds, the latter showing means dispersal distances from 421-5003 kilometers. These findings strongly highlight the potential role of migratory birds in the epidemiology of tick-borne pathogens.

Disparate Impact: How Does Social Deprivation Affect Patient-reported Outcomes After ACL Reconstruction in Children and Adolescents?

BACKGROUND: Research has indicated that lower socioeconomic status is associated with delays in the treatment of anterior cruciate ligament (ACL) injuries; however, there is a paucity of literature evaluating its association with patient-reported outcomes (PROs). Using the Area Deprivation Index (ADI), a validated proxy for socioeconomic status, the study aimed to determine how relative socioeconomic disadvantage is related to PROs after primary ACL reconstruction (ACLR) in pediatric patients. METHODS: This retrospective cohort study included all patients 18 years old or above who underwent primary ACLR at an academic institution between 2018 and 2021. Exclusion criteria included multiligament injury, congenital ACL absence, and absent outcomes data. The minimum follow-up was 6 months. A Patient-reported Outcomes Measurement Information System (PROMIS) 50 Pediatric self-report questionnaire was completed at postoperative visits, and domain scores for pain, physical function/mobility, fatigue, anxiety, depression, and peer relationships were generated. The National ADI percentile was calculated using the patients' addresses. Patients were divided into quartiles (low, moderate, moderate-severe, and severe ADI), and comparative analyses were performed to determine the relationship between ADI and PROMIS. RESULTS: A total of 413 patients were identified, including 49% (n=207), 33% (n=139), 11% (n=48), and 7% (n=30) from the low, moderate, moderate-severe, and severe deprivation areas, respectively. As compared with those in the low-deprivation quartile, patients in the severe deprivation quartile had delayed time to the first clinic visit (11 vs. 16.5 d, P=0.044) and surgery (51 vs. 80 d, P=0.004). There were no differences in the number of additional procedures required at index surgery. All quartiles had progressive improvements in physical function/mobility and pain scores throughout recovery, but at 9 months, there was significantly more pain in the severe deprivation cohort, despite no difference in self-reported physical function and mobility. Those with severe socioeconomic disadvantage had worse psychosocial outcomes, including significantly increased depression, fatigue, and anxiety and decreased peer relationship scores. CONCLUSIONS: Although there were no differences in preoperative PROMIS scores, pediatric patients living in areas with higher levels of socioeconomic deprivation/disadvantage had worse psychosocial PROs after ACLR. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Activation of α 6 -containing GABA A receptors induces antinociception under physiological and pathological conditions.

ABSTRACT: The loss of GABAergic inhibition is a mechanism that underlies neuropathic pain. Therefore, rescuing the GABAergic inhibitory tone through the activation of GABA A receptors is a strategy to reduce neuropathic pain. This study was designed to elucidate the function of the spinal α 6 -containing GABA A receptor in physiological conditions and neuropathic pain in female and male rats. Results show that α 6 -containing GABA A receptor blockade or transient α 6 -containing GABA A receptor knockdown induces evoked hypersensitivity and spontaneous pain in naive female rats. The α 6 subunit is expressed in IB4 + and CGRP + primary afferent neurons in the rat spinal dorsal horn and dorsal root ganglia but not astrocytes. Nerve injury reduces α 6 subunit protein expression in the central terminals of the primary afferent neurons and dorsal root ganglia, whereas intrathecal administration of positive allosteric modulators of the α 6 -containing GABA A receptor reduces tactile allodynia and spontaneous nociceptive behaviors in female, but not male, neuropathic rats and mice. Overexpression of the spinal α 6 subunit reduces tactile allodynia and restores α 6 subunit expression in neuropathic rats. Positive allosteric modulators of the α 6 -containing GABA A receptor induces a greater antiallodynic effect in female rats and mice compared with male rats and mice. Finally, α 6 subunit is expressed in humans. This receptor is found in CGRP + and P2X3 + primary afferent fibers but not astrocytes in the human spinal dorsal horn. Our results suggest that the spinal α 6 -containing GABA A receptor has a sex-specific antinociceptive role in neuropathic pain, suggesting that this receptor may represent an interesting target to develop a novel treatment for neuropathic pain.

The use of functional near infrared spectroscopy and gait analysis to characterize cognitive and motor processing in early-stage patients with multiple sclerosis.

Background: Dual-task paradigms are a known tool to evaluate possible impairments in the motor and cognitive function in patients with multiple sclerosis (MS). A technique to evaluate the cortical function during movement is functional near-infrared spectroscopy (fNIRS). The evaluation of the MS course or its treatment by associating fNIRS with gait measurements may be flexible and low-cost; however, there are no feasibility studies in the literature using these combined techniques in early-stage patients with MS. Objective: To evaluate cortical hemodynamics using fNIRS and gait parameters in patients at early stages of MS and in healthy controls during a dual-task paradigm. Methods: Participants performed cognitive tasks while walking to simulate daily activities. Cortical activation maps and gait variability were used to evaluate differences between 19 healthy controls and 20 patients with MS. Results and conclusion: The results suggest an enhanced cortical activation in the motor planning areas already at the early stages of MS when compared to controls. We have also shown that a systematic analysis of the spatiotemporal gait variability parameters indicates differences in the patient population. The association of cortical and gait parameters may reveal possible compensatory mechanisms related to gait during dual tasking at the early stages of the disease.

Decline in Functional Status While on the Waiting List Predicts Worse Survival After Lung Transplantation.

OBJECTIVES: To determine if decreases in the Karnofsky Performance Score (KPS) while on the waitlist predict decreased survival after lung transplantation (LTx). DESIGN: A retrospective evaluation of the United Network for Organ Sharing database. The KPS was evaluated at the time of listing for transplant and at the time of transplantation. Group I consisted of patients having a decrease in KPS during the time on the waiting list (from the time of listing to the time of transplant), and Group II consisted of patients whose KPS stayed the same or increased during the same period. The authors used propensity-score weighting for comparisons of these groups. SETTING: Retrospective observational database review. PARTICIPANTS: Adult patients undergoing lung transplantation. INTERVENTIONS: None. Patients were stratified according to a change in their KPS. MEASUREMENTS AND MAIN RESULTS: Patient and graft survival of patients with decreasing or not decreasing KPS were compared. Of the 27,558 subjects included in the analysis, 17,986 (65%) had worsening KPS, which was associated with worse graft (p = 0.0003) and patient (p = 0.0019) survival after LTx. Using multivariate regression, a decrease in KPS of ≥40 was associated with decreased survival, and an increase of ≥40 was associated with improved survival (HR = 1.245, 95% CI [1.181-1.312], p < 0.0001 and HR = 0.866, 95% CI [0.785, 0.955], respectively). Among patients with a KPS <40 at the time of transplant, those with a decrease in KPS of ≥40 had decreased graft and patient survival compared with those with a smaller decrease (p = 0.0002 and p = 0.0021, respectively). CONCLUSIONS: Deterioration of KPS on the waiting list for LTx is associated with significantly greater postoperative mortality in patients after LTx. These results should be taken into consideration when allocating organs. Strategies to increase or to prevent a decrease in KPS before LTx should be evaluated.

How Much Will My Child's ACL Reconstruction Cost? Availability and Variability of Price Estimates for Anterior Cruciate Ligament Reconstruction in the United States.

BACKGROUND: Despite recent policy efforts to increase price transparency, obtaining estimated prices for surgery remains difficult for most patients and families. PURPOSE: Assess availability and variability of cost and self-pay discounts for pediatric anterior cruciate ligament (ACL) reconstruction in the United States. METHODS: This was a prospective study using scripted telephone calls to obtain price estimates and self-pay discounts for pediatric ACL reconstruction. From July to August 2020, investigators called 102 hospitals, 51 "top-ranked" pediatric orthopaedic hospitals and 51 "non-top ranked" hospitals randomly selected, to impersonate the parent of an uninsured child with a torn ACL. Hospital, surgeon, and anesthesia price estimates, availability of a self-pay discount, and number of calls and days required to obtain price estimates were recorded for each hospital. Hospitals were compared on the basis of ranking, teaching status, and region. RESULTS: Only 31/102 (30.3%) hospitals provided a complete price estimate. Overall, 52.9% of top-ranked hospitals were unable to provide any price information versus 31.4% of non-top-ranked hospitals ( P =0.027). There was a 6.1-fold difference between the lowest and highest complete price estimates (mean estimate $29,590, SD $14,975). The mean complete price estimate for top-ranked hospitals was higher than for non-top-ranked hospitals ($34,901 vs. $25,207; P =0.07). The mean complete price estimate varied significantly across US region ( P =0.014), with the greatest mean complete price in the Northeast ($41,812). Altogether, 38.2% hospitals specified a self-pay discount, but only a fraction disclosed exact dollar or percentage discounts. The mean self-pay discount from top-ranked hospitals was larger than that of non-top-ranked hospitals ($18,305 vs. $9902; P =0.011). An average of 3.1 calls (range 1.0 to 12.0) over 5 days (range 1 to 23) were needed to obtain price estimates. CONCLUSION: Price estimates for pediatric sports medicine procedures can be challenging to obtain, even for the educated consumer. Top-ranked hospitals and hospitals in the Northeast region may charge more than their counterparts. In all areas, self-pay discounts can be substantial if they can be identified but they potentially create an information disadvantage for unaware patients needing to pay out-of-pocket. STUDY DESIGN: Economic; Level of Evidence II. WHAT IS KNOWN ABOUT THE SUBJECT: Previous studies have highlighted the importance of value-based health care decisions and deficits of price transparency in various fields including pediatric and orthopaedics procedures. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: This study is the first to examine availability and variability of health care cost in pediatric sports medicine and the first to assess availability and magnitude of self-pay discounts, setting expectations for the uninsured patient incurring large out-of-pocket expenses.

The Prevalence of Spiritual and Social Support Needs and Their Association With Postintensive Care Syndrome Symptoms Among Critical Illness Survivors Seen in a Post-ICU Follow-Up Clinic.

OBJECTIVES: Spiritual and social support may be key facilitators for critical illness recovery and are identified as high priority for research. Understanding the prevalence of spiritual and social support needs in critical illness survivors may guide development of targeted interventions for support, which, in turn, may improve critical illness survivor quality of life. To characterize unmet spiritual and social support needs in critical illness survivors approximately 1 month after hospital discharge and examine the association of these needs with postintensive care syndrome (PICS)-related symptom burden. DESIGN: Retrospective, cross-sectional study. SETTING: University-affiliated hospital in Pittsburgh, PA. PATIENTS: One hundred ninety-six consecutive adult critical illness survivors seen during an initial post-ICU clinic visit from June 2018 to March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient-reported clinical outcome measures assessing spiritual and social support needs and PICS-related symptoms were extracted from the electronic health record. Patients had a median age of 61 (interquartile range [IQR], 51-68.5), and majority were male (55.1%) with a moderate comorbidity burden (Charlson comorbidity index median score, 3; IQR, 2-5). Social support and spiritual needs were prevalent. Of the 196 patients, over 50% reported unpreparedness/fearful for the future, half of patients reported not feeling in control of their care, and over one-third reported needing more support than their family, friends, or insurance can provide. Nearly 13% of respondents reported feeling abandoned or punished by God/not supported by their church/faith. Many patients reported overlapping PICS-related symptom domains (physical, psychologic, and cognitive). Univariate and multivariate analyses revealed associations between reported PICS-related symptoms and the presence of spiritual and social needs. CONCLUSIONS: Patients surviving critical illness experience significant social support and spiritual needs independent of commonly identified manifestations of PICS. These findings support the need for formal assessment and tailored interventions for social support and spiritual needs in critical illness survivors.

Trends in Pediatric Anterior Cruciate Ligament Reconstruction: The Effect of COVID-19.

CONTEXT: The number of pediatric anterior cruciate ligament reconstructions (ACLRs) occurring yearly increased almost 6-fold from 2004-2014. We find it interesting that limited recent data exist on rates of ACL injury and reconstruction in children and adolescents, especially in the context of COVID-19. OBJECTIVE: Given the effect of the COVID-19 pandemic on youth sports seasons and the postponement of many elective surgeries, we sought to examine the changes in rates of ACLR during this period. DESIGN: Retrospective cohort study. SETTING: This study used the Pediatric Health Information System (PHIS) database to identify eligible patients at PHIS-participating hospitals nationwide from January 2016-June 2021, with March 1, 2020, considered the start of the COVID-19 pandemic. PATIENTS OR OTHER PARTICIPANTS: Using Current Procedural Terminology codes, patients 18 years old and younger who underwent ACLR surgery were identified. MAIN OUTCOME MEASURE(S): Patient demographics and overall rates of surgery prepandemic and intrapandemic were compared. Data were analyzed using bivariate, mixed-model, and time series analyses. RESULTS: A total of 24 843 ACLRs were identified during this time period. In total, 1853 fewer surgeries than expected were performed after March 2020 given prepandemic trends. Intrapandemic demographics revealed an increase in the proportion of patients who identified as White and with private insurance and a decrease in the proportion who identified as Black and with public insurance. Also, the proportion of ACLRs by region shifted, with more surgeries performed in the Midwest and fewer in the Northeast. In the model adjusted for hospital-level variability, only race and insurance status remained significant. CONCLUSIONS: Based on prepandemic trends, fewer patients than projected underwent ACLR once the pandemic began, likely due to a combination of decreased rates of injury and delayed surgery.

Neonatal Reference Intervals for the Complete Blood Count Parameters MicroR and HYPO-He: Sensitivity Beyond the Red Cell Indices for Identifying Microcytic and Hypochromic Disorders.

OBJECTIVE: To create neonatal reference intervals for the MicroR and HYPO-He complete blood count (CBC) parameters and to test whether these parameters are sensitive early markers of disease at early stages of microcytic/hypochromic disorders while the CBC indices are still normal. STUDY DESIGN: We retrospectively collected the CBC parameters MicroR and HYPO-He, along with the standard CBC parameters, from infants aged 0-90 days at Intermountain Healthcare hospitals using Sysmex hematology analyzers. We created reference intervals for these parameters by excluding values from neonates with proven microcytic disorders (ie, iron deficiency or alpha thalassemia) from the dataset. RESULT: From >11 000 CBCs analyzed, we created reference intervals for MicroR and HYPO-He in neonates aged 0-90 days. The upper intervals are considerably higher in neonates than in adults, validating increased anisocytosis and polychromasia among neonates. Overall, 52% of neonates with iron deficiency (defined by reticulocyte hemoglobin equivalent <25 pg) had a MicroR >90% upper interval (relative risk, 4.14; 95% CI, 3.80-4.53; P < .001), and 68% had an HYPO-He >90% upper interval (relative risk, 6.64; 95% CI, 6.03-7.32; P < .001). These 2 new parameters were more sensitive than the red blood cell (RBC) indices (P < .001) in identifying 24 neonates with iron deficiency at birth. CONCLUSIONS: We created neonatal reference intervals for MicroR and HYPO-He. Although Sysmex currently designates these as research use only in the US, they can be measured as part of a neonate's CBC with no additional phlebotomy volume or run time and can identify microcytic and hypochromic disorders even when the RBC indices are normal.

Scarce Resource Allocation in a Pandemic: A Protocol to Promote Equity, Timeliness, and Transparency.

Shortages of equipment, medication, and staff under coronavirus disease 2019 may force hospitals to make wrenching decisions. Although bioethical guidance is available, published procedures for decision-making processes to resolve the time-sensitive conflicts are rare. Failure to establish decision-making procedures before scarcities arise exposes clinicians to moral distress and potential legal liability, entrenches existing systemic biases, and leaves hospitals without processes to guarantee transparency and consistency in the application of ethical guidelines. Formal institutional processes can reduce the panic, inequity, and irresolution that arise from confronting ethical conflicts under duress. Drawing on expertise in critical care medicine, bioethics, and political science, we propose a decision-making protocol to ensure fairness in the resolution of conflict, timely decision-making, and accountability to improve system response.

Role of portable ultrasound during a short-term medical service trip to rural Guatemala: a collaborative mission of trainees and physicians.

INTRODUCTION: Access to health care in developing countries is scarce. One solution to this problem has been for doctors from the USA to provide single-visit care through short-term medical service trips. There is interest in using ultrasound imaging as a portable diagnostic tool; however, data describing its usefulness are scarce. Therefore, the goal of this study was to determine the usefulness of portable ultrasound imaging during a medical service trip to rural Guatemala. METHODS: A multidisciplinary team of physicians examined patients at a mobile clinic in Antigua, Guatemala. Patients with clinical indications for ultrasound had their suspected diagnoses recorded before ultrasound testing. After imaging, updated diagnoses were recorded and compared with the pre-test suspected diagnoses to determine how often ultrasound results changed the medical management of the patients and to assess the most common indications for ultrasound imaging. RESULTS: During the trip, 205 patients were seen. Of these, 24 (12%) were given ultrasound exams. The results of 13 (54%) exams altered their medical management, and the remaining 11 (46%) exams confirmed the pre-test suspected diagnoses. The most common indications for ultrasound testing were suspected cardiac (11 patients, 46%) and gastrointestinal (8 patients, 33%) diseases. CONCLUSION: Portable ultrasound imaging improved the medical team's ability to diagnose disease and clinically manage patients in a rural medical service trip. Ultrasound imaging may provide a low-cost solution to the growing demand for care in developing countries.

Anesthetic Considerations for a Novel Method of Surgical Ventricular Remodeling Using the BioVentrix Revivent TC System.

Surgical ventricular remodeling (SVR) is an invasive method of treating patients with heart failure who also have ischemic cardiomyopathy and reduced ejection fraction (EF). Introduced in the mid-1980s, this technique was met with varying success and relatively high morbidity and mortality despite its theoretical benefits. The development of the BioVentrix Revivent TC System (BioVentrix, Inc., San Ramon, CA) as a less-invasive method of surgical ventricular remodeling has created a novel, multidisciplinary approach to heart failure management, which necessitates multiple subspecialties. Currently in the trial phase in the United States and widely used in Europe, the positive results to date appear promising for the rapid adoption of this procedure. For the cardiac anesthesiologist, a thorough understanding of the patient population, procedural goals, and intraoperative management is essential. This overview discusses the advancement in surgical ventricular remodeling, the pertinent surgical steps of the BioVentrix Revivent TC System placement, and specific anesthetic considerations for this novel procedure.

Sex-dependent pronociceptive role of spinal α5 -GABAA receptor and its epigenetic regulation in neuropathic rodents.

Extrasynaptic α5 -subunit containing GABAA (α5 -GABAA ) receptors participate in chronic pain. Previously, we reported a sex difference in the action of α5 -GABAA receptors in dysfunctional pain. However, the underlying mechanisms remain unknown. The aim of this study was to examine this sexual dimorphism in neuropathic rodents and the mechanisms involved. Female and male Wistar rats or ICR mice were subjected to nerve injury followed by α5 -GABAA receptor inverse agonist intrathecal administration, L-655,708. The drug produced an antiallodynic effect in nerve-injured female rats and mice, and a lower effect in males. We hypothesized that changes in α5 -GABAA receptor, probably influenced by hormonal and epigenetic status, might underlie this sex difference. Thus, we performed qPCR and western blot. Nerve injury increased α5 -GABAA mRNA and protein in female dorsal root ganglia (DRG) and decreased them in DRG and spinal cord of males. To investigate the hormonal influence over α5 -GABAA receptor actions, we performed nerve injury to ovariectomized rats and reconstituted them with 17ß-estradiol (E2). Ovariectomy abrogated L-655,708 antiallodynic effect and E2 restored it. Ovariectomy decreased α5 -GABAA receptor and estrogen receptor α protein in DRG of neuropathic female rats, while E2 enhanced them. Since DNA methylation might contribute to α5 -GABAA receptor down-regulation in males, we examined CpG island DNA methylation of α5 -GABAA receptor coding gene through pyrosequencing. Nerve injury increased methylation in male, but not female rats. Pharmacological inhibition of DNA methyltransferases increased α5 -GABAA receptor and enabled L-655,708 antinociceptive effect in male rats. These results suggest that α5 -GABAA receptor is a suitable target to treat chronic pain in females.

Society of Critical Care Medicine's International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness.

BACKGROUND: After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when remain unclear. OBJECTIVES: Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for postdischarge impairments. PARTICIPANTS: Thirty-one international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine's Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers. DESIGN: Society of Critical Care Medicine consensus conference on post-intensive care syndrome prediction and assessment, held in Dallas, in May 2019. A systematic search of PubMed and the Cochrane Library was conducted in 2018 and updated in 2019 to complete an original systematic review and to identify pre-existing systematic reviews. MEETING OUTCOMES: We concluded that existing tools are insufficient to reliably predict post-intensive care syndrome. We identified factors before (e.g., frailty, preexisting functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2-4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment test; Hospital Anxiety and Depression Scale; Impact of Event Scale-Revised (post-traumatic stress disorder); 6-minute walk; and/or the EuroQol-5D-5L, a health-related quality of life measure (physical function). CONCLUSIONS: Beginning with an assessment of a patient's pre-ICU functional abilities at ICU admission, clinicians have a care coordination strategy to identify and manage impairments across the continuum. As hospital discharge approaches, clinicians should use brief, standardized assessments and compare these results to patient's pre-ICU functional abilities ("functional reconciliation"). We recommend serial assessments for post-intensive care syndrome-related problems continue within 2-4 weeks of hospital discharge, be prioritized among high-risk patients, using the identified screening tools to prompt referrals for services and/or more detailed assessments.

Sex differences in the role of atypical PKC within the basolateral nucleus of the amygdala in a mouse hyperalgesic priming model.

Though sex differences in chronic pain have been consistently described in the literature, their underlying neural mechanisms are poorly understood. Previous work in humans has demonstrated that men and women differentially invoke distinct brain regions and circuits in coping with subjective pain unpleasantness. The goal of the present work was to elucidate the molecular mechanisms in the basolateral nucleus of the amygdala (BLA) that modulate hyperalgesic priming, a pain plasticity model, in males and females. We used plantar incision as the first, priming stimulus and prostaglandin E2 (PGE2) as the second stimulus. We sought to assess whether hyperalgesic priming can be prevented or reversed by pharmacologically manipulating molecular targets in the BLA of male or female mice. We found that administering ZIP, a cell-permeable inhibitor of aPKC, into the BLA attenuated aspects of hyperalgesic priming induced by plantar incision in males and females. However, incision only upregulated PKCζ/PKMζ immunoreactivity in the BLA of male mice, and deficits in hyperalgesic priming were seen only when we restricted our analysis to male Prkcz-/- mice. On the other hand, intra-BLA microinjections of pep2m, a peptide that interferes with the trafficking and function of GluA2-containing AMPA receptors, a downstream target of aPKC, reduced mechanical hypersensitivity after plantar incision and disrupted the development of hyperalgesic priming in both male and female mice. In addition, pep2m treatment reduced facial grimacing and restored aberrant behavioral responses in the sucrose splash test in male and female primed mice. Immunofluorescence results demonstrated upregulation of GluA2 expression in the BLA of male and female primed mice, consistent with pep2m findings. We conclude that, in a model of incision-induced hyperalgesic priming, PKCζ/PKMζ in the BLA is critical for the development of hyperalgesic priming in males, while GluA2 in the BLA is crucial for the expression of both reflexive and affective pain-related behaviors in both male and female mice in this model. Our findings add to a growing body of evidence of sex differences in molecular pain mechanisms in the brain.

Collection of Common Knee Patient-reported Outcome Instruments by Automated Mobile Phone Text Messaging in Pediatric Sports Medicine.

BACKGROUND: Patient-reported outcome (PRO) instruments measure health status in a variety of domains. With the proliferation of mobile phones, delivering PROs across patient-friendly platforms (eg, apps, text messaging) may increase completion rates, particularly among children. The purpose of this study was to validate the collection of common knee PROs in sports medicine with text messaging by correlating text-messaging responses with paper delivery in adolescents. METHODS: Patients presenting to a hospital-based pediatric orthopaedic sports medicine clinic with a knee injury were enrolled prospectively. Paper versions of the Pediatric International Knee Documentation Committee (Pedi-IKDC) Subjective Knee Evaluation Form and the Pediatric Functional Activity Brief Scale (Pedi-Fab Scale) were completed during initial clinic visits. Over the next 72 hours, patients completed the text message delivery of the Pedi-IKDC and Pedi-Fab Scale. Correlations between paper and text message delivery of the 2 PROs were assessed. RESULTS: Ninety-one patients (mean age: 16.0±2.0 y; 48% females) enrolled in the text-messaging study, with 55 (60.4%) completing the Pedi-Fab Scale, 48 (52.7%) completing the Pedi-IKDC, and 39 (42.9%) completing both PROs. The intraclass correlation coefficient between the paper and mobile phone delivery of the Pedi-Fab Scale was 0.95 (P<0.001; 95% confidence interval, 0.91-0.97). The intraclass correlation coefficient between the paper and mobile phone delivery of the Pedi-IKDC was 0.96 (P<0.001; 95% confidence interval, 0.93-0.98). Average Pedi-Fab scores on paper (M=12.7) and mobile phone (M=12.3) were not significantly different (P=0.52). Similarly, average Pedi-IKDC scores on paper (M=68.8) and mobile phone (M=67.7) were not significantly different (P=0.41). Average completion time for the text delivered Pedi-Fab and Pedi-IKDC were 102±224 and 159±155 minutes, respectively. High school enrollment (P=0.025), female sex (P=0.036), and race (P=0.002) were significantly associated with text completion of Pedi-IKDC. CONCLUSIONS: Text message delivery using mobile phones permits valid assessment of Pedi-IKDC and Pedi-Fab scores in adolescents. Questionnaire delivery by automated text messaging allows asynchronous response and may increase compliance and reduce the labor cost of collecting PROs. LEVEL OF EVIDENCE: Level III-prospective cohort study.

Salmonella enterica Serotype Panama: An exceptionally virulent cause of illness in children?

Salmonella enterica serotype Panama accounts for <1% of all reported cases of Salmonellosis. Previous reports suggest that it may be unusually virulent in children. We report the case of a family, five of six of whom developed a diarrheal illness due to this organism following exposure during a trip to Costa Rica. Included among these patients were three children, all of whom developed clinical shock requiring aggressive fluid resuscitation, and all of whom ultimately recovered. DNA fingerprinting, using pulsed-field gel electrophoresis, demonstrated that all three children were infected with an identical strain of Salmonella. Moreover, this strain was unique among strains recovered in Nebraska. Clinicians should be aware of the propensity of Salmonella enterica serotype Panama to cause especially severe disease in children; laboratory personnel should be aware of the unique need for thiourea buffering when attempting to perform pulsed-field gel electrophoresis analysis on such strains.

All-epiphyseal Anterior Cruciate Ligament Reconstruction Does Not Increase the Risk of Complications Compared With Pediatric Transphyseal Reconstruction.

INTRODUCTION: Complication rates after physeal-sparing anterior cruciate ligament reconstruction (ACLR) are known to be high in the paediatric population compared with the adult population. However, the outcomes of these skeletally immature patients after all-epiphyseal reconstruction have not been compared with those after transphyseal reconstructions in a more similar age group. This study compares clinical outcomes and complications between all-epiphyseal and pediatric transphyseal ACLR. METHODS: We retrospectively reviewed 1,056 pediatric patients undergoing primary ACLR between 2000 and 2015. Of these, 51 were excluded (5 extra-articular and 46 partial transphyseal reconstructions). Demographic data, intraoperative findings and techniques, postoperative complications (including graft rupture, contralateral anterior cruciate ligament [ACL] tear, and meniscus injuries), clearance for sports, range of motion (ROM), and isokinetic strength testing were recorded. Univariate analysis was followed by stepwise, binary logistic regressions to control for confounding factors. RESULTS: During the study period, 162 patients underwent all-epiphyseal reconstruction (mean age, 12.1 ± 1.8 years) and 843 underwent transphyseal ACLR (mean age, 15.8 ± 1.9 years). At the time of surgery, more meniscus tears were found in the transphyseal group (76% versus 60%; P < 0.01). These patients also had more irreparable meniscus tears requiring partial meniscectomy (35% versus 18%; P < 0.01). Overall, the rates of graft failure, contralateral ACL injury, and new meniscus tears were 10.3%, 6.1%, and 14.2%, respectively. After controlling for confounders in a multivariate model, no difference was found in these postoperative complications between all-epiphyseal and transphyseal ACLR. Furthermore, no clinically significant difference was observed in postoperative ROM or isokinetic strength testing. DISCUSSION: Skeletally immature patients undergoing all-epiphyseal ACLR had less irreparable meniscus tears than older children undergoing transphyseal reconstruction. After adjusting for age and other confounders, there was no difference in postoperative ROM or strength, nor an increased risk of graft rupture, contralateral ACL injury, or new meniscus tear in these young patients compared with older adolescents undergoing transphyseal ACLR. LEVEL OF EVIDENCE: Level III.