Caring for Domestic Minor Sex Trafficking Patients: Recommendations for Identification, Interventions, and Resources.

Domestic minor sex trafficking has increasingly gained awareness as a social phenomenon that affects adolescent health and safety. Healthcare providers are uniquely positioned to identify and facilitate supportive interventions for adolescents at high risk or involved in trafficking. A growing literature base and clinical experience provide recommendations on how to identify, engage trafficked youth, and provide beneficial linkages with community resources. A coordinated, multidisciplinary, and trauma-informed response that fosters therapeutic alliances promoting agency, safety, and trust are key components of successful care for this vulnerable adolescent population.

Female Caregivers' Perception of their Child's Sexualized Behaviors: A Pilot Study at a Child Protection Clinic.

This pilot study explored female caregiver's perception of their child's behaviors during sexual abuse evaluations. We compared reports by caregivers with histories of their own child sexual abuse (PCSA) to caregivers with no prior history of child sexual abuse (NPCSA) regarding their 1) child's sexualized behaviors and (2) perceptions of whether their child had been sexually abused. Forty-four caregivers met inclusion criteria. Ninety-five percent of PCSA caregivers versus 21% of NPCSA caregivers reported at least one behavior from the Child Sexual Behavior Inventory. Our findings identified that PCSA caregivers reported more sexualized behaviors for their children overall, potentially contributing to their perception that their child had been sexually abused. This pilot study demonstrated that caregivers were able to tolerate answering questions about their own history of child abuse. Parents should be asked these questions as this may influence perceptions of their child's behaviors and possible sexual abuse.

A Unique Canine Comfort Therapy Program for Child Maltreatment Cases.

Research has shown that programs utilizing comfort therapy canines in cases of child maltreatment have been successful in providing valuable support to children and their families. To date these programs have made canine comfort therapy dogs available solely within one of the involved disciplines. Therefore, a unique canine comfort therapy program was established specifically to support this pediatric population by implementing a collaborative canine comfort therapy program within two separate disciplines. CALI (Cranston Police, Aubin Center, Leadership in Innovation) was the first official K-9 comfort therapy dog in a police department in Rhode Island (RI), and the first employed dog within the state's only children's hospital. This program provides a longitudinal experience that supports children and their families by fostering a sense of familiarity and trust throughout all the difficult components of a child maltreatment case (e.g., evaluation, treatment, investigation and prosecution).

A Guide to MALDI Imaging Mass Spectrometry for Tissues.

Imaging mass spectrometry is a well-established technology that can easily and succinctly communicate the spatial localization of molecules within samples. This review communicates the recent advances in the field, with a specific focus on matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) applied on tissues. The general sample preparation strategies for different analyte classes are explored, including special considerations for sample types (fresh frozen or formalin-fixed,) strategies for various analytes (lipids, metabolites, proteins, peptides, and glycans) and how multimodal imaging strategies can leverage the strengths of each approach is mentioned. This work explores appropriate experimental design approaches and standardization of processes needed for successful studies, as well as the various data analysis platforms available to analyze data and their strengths. The review concludes with applications of imaging mass spectrometry in various fields, with a focus on medical research, and some examples from plant biology and microbe metabolism are mentioned, to illustrate the breadth and depth of MALDI IMS.

Prospective on Imaging Mass Spectrometry in Clinical Diagnostics.

Imaging mass spectrometry (IMS) is a molecular technology utilized for spatially driven research, providing molecular maps from tissue sections. This article reviews matrix-assisted laser desorption ionization (MALDI) IMS and its progress as a primary tool in the clinical laboratory. MALDI mass spectrometry has been used to classify bacteria and perform other bulk analyses for plate-based assays for many years. However, the clinical application of spatial data within a tissue biopsy for diagnoses and prognoses is still an emerging opportunity in molecular diagnostics. This work considers spatially driven mass spectrometry approaches for clinical diagnostics and addresses aspects of new imaging-based assays that include analyte selection, quality control/assurance metrics, data reproducibility, data classification, and data scoring. It is necessary to implement these tasks for the rigorous translation of IMS to the clinical laboratory; however, this requires detailed standardized protocols for introducing IMS into the clinical laboratory to deliver reliable and reproducible results that inform and guide patient care.

Cell cycle controls long-range calcium signaling in the regenerating epidermis.

Skin homeostasis is maintained by stem cells, which must communicate to balance their regenerative behaviors. Yet, how adult stem cells signal across regenerative tissue remains unknown due to challenges in studying signaling dynamics in live mice. We combined live imaging in the mouse basal stem cell layer with machine learning tools to analyze patterns of Ca2+ signaling. We show that basal cells display dynamic intercellular Ca2+ signaling among local neighborhoods. We find that these Ca2+ signals are coordinated across thousands of cells and that this coordination is an emergent property of the stem cell layer. We demonstrate that G2 cells are required to initiate normal levels of Ca2+ signaling, while connexin43 connects basal cells to orchestrate tissue-wide coordination of Ca2+ signaling. Lastly, we find that Ca2+ signaling drives cell cycle progression, revealing a communication feedback loop. This work provides resolution into how stem cells at different cell cycle stages coordinate tissue-wide signaling during epidermal regeneration.

Selective Skeletal Surveys for Infants With Skull Fractures: Examining the Rates of Return to Medical Care for Concern of Physical Abuse.

OBJECTIVES: This study aimed to describe which infants with a skull fracture (1) receive a child abuse pediatrician (CAP) consultation, (2) receive a skeletal survey, and (3) re-present to medical care before age 3 years with concerns for physical abuse. METHODS: We conducted a retrospective chart review of infants younger than 12 months who presented to the emergency department between January 1, 2005, and December 30, 2015, with a skull fracture. Medical records were reviewed for the skull fracture presentation and for all future medical evaluations at the same institution with concerns for physical abuse until 3 years of age. RESULTS: Of 366 infants with a skull fracture, a CAP was contacted for 272 (74%) and 76 (20.8%) infants who received a skeletal survey. Factors associated with skeletal survey acquisition included younger age (<6 months), no history to explain the skull fracture, other injuries on examination, and social risk factors. Six children (1.6%) re-presented to medical care with concerns of physical abuse before age 3 years. Five of these infants did not have a skeletal survey at the time of their skull fracture, and 1 was likely a case of missed physical abuse at the time of the skull fracture. DISCUSSION: Most skull fractures in infancy occur accidentally, and a skeletal survey may not be necessary for every infant. Obtaining a thorough history including social risk factors, performing a complete physical examination, and consulting with a CAP is an effective first step in the evaluation of physical abuse in infants with skull fractures.

Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma.

There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome this challenge by providing insight into sarcomas' molecular drivers. Through targeted panel sequencing of 7494 sarcomas representing 44 histologies, we identify highly recurrent and type-specific alterations that aid in diagnosis and treatment decisions. Sequencing could lead to refinement or reassignment of 10.5% of diagnoses. Nearly one-third of patients (31.7%) harbor potentially actionable alterations, including a significant proportion (2.6%) with kinase gene rearrangements; 3.9% have a tumor mutational burden ≥10 mut/Mb. We describe low frequencies of microsatellite instability (<0.3%) and a high degree of genome-wide loss of heterozygosity (15%) across sarcomas, which are not readily explained by homologous recombination deficiency (observed in 2.5% of cases). In a clinically annotated subset of 118 patients, we validate actionable genetic events as therapeutic targets. Collectively, our findings reveal the genetic landscape of human sarcomas, which may inform future development of therapeutics and improve clinical outcomes for patients with these rare cancers.

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model.

BACKGROUND: The definitive diagnosis of melanocytic neoplasia using solely histopathologic evaluation can be challenging. Novel techniques that objectively confirm diagnoses are needed. This study details the development and validation of a melanoma prediction model from spatially resolved multivariate protein expression profiles generated by imaging mass spectrometry (IMS). METHODS: Three board-certified dermatopathologists blindly evaluated 333 samples. Samples with triply concordant diagnoses were included in this study, divided into a training set (n = 241) and a test set (n = 92). Both the training and test sets included various representative subclasses of unambiguous nevi and melanomas. A prediction model was developed from the training set using a linear support vector machine classification model. RESULTS: We validated the prediction model on the independent test set of 92 specimens (75 classified correctly, 2 misclassified, and 15 indeterminate). IMS detects melanoma with a sensitivity of 97.6% and a specificity of 96.4% when evaluating each unique spot. IMS predicts melanoma at the sample level with a sensitivity of 97.3% and a specificity of 97.5%. Indeterminate results were excluded from sensitivity and specificity calculations. CONCLUSION: This study provides evidence that IMS-based proteomics results are highly concordant to diagnostic results obtained by careful histopathologic evaluation from a panel of expert dermatopathologists.

Skin-resident immune cells actively coordinate their distribution with epidermal cells during homeostasis.

Organs consist of multiple cell types that ensure proper architecture and function. How different cell types coexist and interact to maintain their homeostasis in vivo remains elusive. The skin epidermis comprises mostly epithelial cells, but also harbours Langerhans cells (LCs) and dendritic epidermal T cells (DETCs). Whether and how distributions of LCs and DETCs are regulated during homeostasis is unclear. Here, by tracking individual cells in the skin of live adult mice over time, we show that LCs and DETCs actively maintain a non-random spatial distribution despite continuous turnover of neighbouring basal epithelial cells. Moreover, the density of epithelial cells regulates the composition of LCs and DETCs in the epidermis. Finally, LCs require the GTPase Rac1 to maintain their positional stability, density and tiling pattern reminiscent of neuronal self-avoidance. We propose that these cellular mechanisms provide the epidermis with an optimal response to environmental insults.

An orthogonal methods assessment of topical drug concentrations in skin and the impact for risk assessment in the viable epidermis.

Systemic toxicity assessments for oral or parenteral drugs often utilize the concentration of drug in plasma to enable safety margin calculations for human risk assessment. For topical drugs, there is no standard method for measuring drug concentrations in the stratum basale of the viable epidermis. This is particularly important since the superficial part of the epidermis, the stratum corneum (SC), is nonviable and where most of a topically applied drug remains, never penetrating deeper into the skin. We investigated the relative concentrations of a prototype kinase inhibitor using punch biopsy, laser capture microdissection, and imaging mass spectrometry methods in the SC, stratum basale, and dermis of minipig skin following topical application as a cream formulation. The results highlight the value of laser capture microdissection and mass spectrometry imaging in quantifying the large difference in drug concentration across the skin and even within the epidermis, and supports use of these methods for threshold-based toxicity risk assessments in specific anatomic locations of the skin, like of the stratum basale.

Impact of temperature-dependent phage expression on Pseudomonas aeruginosa biofilm formation.

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that forms robust biofilms in the different niches it occupies. Numerous physiological adaptations are required as this organism shifts from soil or aquatic environments to a host-associated lifestyle. While many conditions differ between these niches, temperature shifts are a factor that can contribute to physiological stress during this transition. To understand how temperature impacts biofilm formation in this pathogen, we used proteomic and transcriptomic tools to elucidate physiological responses in environment-relevant vs. host-relevant temperatures. These studies uncovered differential expression of various proteins including a phage protein that is associated with the EPS matrix in P. aeruginosa. This filamentous phage was induced at host temperatures and was required for full biofilm-forming capacity specifically at human body temperature. These data highlight the importance of temperature shift in biofilm formation and suggest bacteriophage proteins could be a possible therapeutic target in biofilm-associated infections.

Substance Use in a Domestic Minor Sex Trafficking Patient Population.

ABSTRACT: Substance use and abuse have been documented as both a risk factor in and consequence of involvement in domestic minor sex trafficking (DMST). Domestic minor sex trafficking is defined as the commercial sexual exploitation of children in exchange for money, food, shelter, or any other valued entity. The current investigation sought to describe substance use in a cohort of DMST patients who present for medical evaluation. Findings revealed that 68 patients referred for DMST involvement reported high rates of alcohol/substance use and parental substance abuse. Further, many patients who had a urine toxicology screen had a positive result, most often identifying the presence of cannabinoids. Our data may inform the importance of comprehensive assessments and specialized interventions for substance abuse in this unique patient population.

Pediatric Rib Fractures Identified by Chest Radiograph: A Comparison Between Accidental and Nonaccidental Trauma.

OBJECTIVE: The objective of this study was to determine the prevalence of rib fractures (RFs) identified by chest x-ray (CXR) among children younger than 2 years who sustained accidental versus nonaccidental injuries. It is hypothesized that RFs are uncommon among all accidental pediatric trauma mechanisms (eg, falls, motor vehicle crashes) as compared with the prevalence of RFs in the setting of nonaccidental trauma (NAT). METHODS: A retrospective chart review of sequential CXRs of children younger than 2 years evaluated at a pediatric level 1 trauma center for accidental trauma and possible NAT was conducted from January 1, 2011, to October 31, 2016. Data collected included demographics, CXR indication and findings, history of cardiopulmonary resuscitation, trauma mechanism, associated injuries, final diagnoses, and outcomes. RESULTS: Two (<1%) of 226 CXRs obtained to evaluate accidental trauma demonstrated acute RFs. Ten (19.6%) of 51 CXRs obtained in the setting of concern for NAT revealed RFs (9/10 identified only healing RFs and 1/10 identified acute RFs). Among patients with a final diagnosis of NAT (ie, not neglect, accidental trauma, etc; n = 38), the overall prevalence increased to 26.3%. CONCLUSIONS: The presence of RFs in pediatric accidental trauma is uncommon even in the setting of high-force mechanisms, and when identified, these RFs are acute. Comparatively, the overall prevalence of RFs identified on CXR among cases with a final diagnosis of NAT was much higher and almost exclusively healing RFs. These data provide support that identification of RFs is highly concerning for NAT even if an accidental mechanism is provided. When RFs are identified, a full NAT work-up should be considered.

A Comprehensive Pediatric Acute Sexual Assault Protocol: From Emergency Department to Outpatient Follow-up.

OBJECTIVE: Close medical follow-up after pediatric acute sexual assault is recommended and may mitigate adverse consequences and decrease long-term comorbidities. The objectives are to (1) examine adherence to a comprehensive outpatient medical follow-up protocol after evaluation in the emergency department in a pediatric population and (2) identify characteristics associated with patient adherence to inform the utilization of a medical follow-up protocol after pediatric acute sexual assault. METHODS: A retrospective medical record review was conducted of patients younger than 18 years presenting to the emergency department from January 1, 2010, to December 31, 2013, with a discharge diagnosis suggestive of sexual assault/abuse. We examined differences in demographics, assault characteristics, and medical/legal needs of patients who were evaluated in follow-up versus patients who were not. RESULTS: Of 182 patients, 60.4% completed follow-up appointments with the child protection center. Younger patients had follow-up rates higher than older patients (70.2% vs 50%; odds ratio [OR], 0.42). For patients where child protective services or law enforcement were called, follow-up rates were 74.2% and 64.7%, respectively (OR, 2.5; OR, 3.1). All patients with anogenital injuries on initial examination were seen in follow-up. The majority of patients who followed-up were accompanied by a caregiver/relative (95%). CONCLUSIONS: (1) Caregivers should be integrated into the evaluation to facilitate compliance with follow-up; (2) child abuse specialists may be consulted to facilitate specific interventions and recommendations; (3) professionals should work as a multidisciplinary team; and (4) the patient's psychological status should be evaluated, and mental health interventions recommended.

When Parents Hit: Providing Education to Physician Trainees About Corporal Punishment Through a Pilot Simulation and Debriefing.

OBJECTIVES: No studies have evaluated how training physicians intervene when corporal punishment (CP) is observed in a simulated hospital setting. The pilot study examined physician trainee performance in a simulation where hitting is observed between caregiver and child during a medical visit and to assess physician self-reported experiences, opinions, and comfort when observing CP in a simulation. METHODS: We ran 7 simulations where one pediatric resident, emergency medicine resident, or pediatric emergency medicine fellow participated in the simulation while a group of similar trainees observed. All participants were given a postsurvey, followed by a semistructured debriefing led by a child abuse pediatrician. RESULTS: Thirty-seven physician trainees participated; 7 engaged in the simulation while 30 observed. The majority (6/7) did not de-escalate the increasingly aggravated parent prior to hitting, 4 of 7 did not recommend that the caregiver refrain from CP, and most (5/7) did not provide education to the parent about more appropriate discipline. The majority (91.4%) believe that a physician should intervene when a parent hits or spanks his/her child in the hospital setting, highlighting the incongruity between this belief and their performance in/knowledge of intervening. All participants stated they would benefit from additional education and training on CP. CONCLUSIONS: The educational experience provided physicians in training with the opportunity to participate in or observe a situation in which CP occurs in the medical setting. The simulation and debriefing were an innovative approach to providing an educational opportunity for physicians to learn from difficult situations and discussions surrounding CP with caregivers.

Trafficking Experiences and Psychosocial Features of Domestic Minor Sex Trafficking Victims.

Domestic minor sex trafficking (DMST) is an increasingly recognized traumatic crime premised upon the control, abuse, and exploitation of youth. By definition, DMST is the "recruitment, harboring, transportation, provision, or obtaining of a person for the purpose of a commercial sex act" within domestic borders, in which the person is a U.S. citizen or lawful permanent resident under the age of 18 years. The present study described the demographics, psychosocial features, and trafficking experiences (e.g., environments of recruitment, relationship to trafficker, solicitation) of DMST victims. A total of 25 medical records of patients under the age of 18 who disclosed their involvement in DMST to medical providers between August 1, 2013, and November 30, 2015, were retrospectively reviewed. The majority of patients were female, and the mean age was 15.4 years old. Most patients lived at home and/or were accompanied at the evaluation by a parent/guardian. High rates of alcohol or substance use/abuse (92%), being placed in a group home or child protective services (CPS) custody (28%), a history of runaway behavior (60%), and/or exposure to other child maltreatment (88%) were identified. Our data indicated variation in reported trafficking experiences; however, patients commonly reported an established relationship with their trafficker (60%) and recruitment occurred primarily as a result of financial motivation (52%). Patients were prevalently recruited in settings where there were face-to-face interactions (56%), whereas the solicitation of sex-buyers occurred primarily online (92%). Victims who disclosed involvement in DMST had complicated psychosocial histories that may have rendered them susceptible to their exploitation, and reported a variety of DMST experiences perpetuated by traffickers. Although preliminary in nature, this study provided empirical evidence of the predisposing factors, motivations, and experiences of victimized youth uniquely from the perspective of patients who sought medical care.