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The fusion gene MLL-AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukaemia. However, relapse can be associated with a switch from acute lymphoblastic to acute myeloid leukaemia. Here we show that these myeloid relapses share oncogene fusion breakpoints with their matched lymphoid presentations and can originate in either early, multipotent progenitors or committed B-cell precursors. Lineage switching is linked to substantial changes in chromatin accessibility and rewiring of transcriptional programmes indicating that the execution and maintenance of lymphoid lineage differentiation is impaired. We show that this subversion is recurrently associated with the dysregulation of repressive chromatin modifiers, notably the nucleosome remodelling and deacetylation complex, NuRD. In addition to mutations, we show differential expression or alternative splicing of NuRD members and other genes is able to reprogram the B lymphoid into a myeloid gene regulatory network. Lineage switching in MLL-AF4 leukaemia is therefore driven and maintained by defunct epigenetic regulation.Statement of SignificanceWe demonstrate diverse cellular origins of lineage switched relapse within MLL-AF4 pro-B acute leukaemia. Irrespective of the developmental origin of relapse, dysregulation of NuRD and/or other epigenetic machinery underpins fundamental lineage reprogramming with profound implications for the increasing use of epitope directed therapies in this high-risk leukaemia.

Noncommunicable diseases (NCDs) place a huge burden on healthcare systems and society as a whole. Relatively early in the coronavirus disease 2019 (COVID-19) pandemic, clinicians became aware that in individuals infected with COVID-19, those with preexisting NCDs such as diabetes mellitus and cardiovascular disease (CVD) were at a greater risk of poor outcomes and mortality than those without. The importance of adherence to medications and lifestyle changes to control and prevent NCDs has been a major focus for many years, but with limited success – the proportion of patients adherent and persistent to their medications remains very low. There are many facets to adherence and persistence. Recent evidence suggests that a patient-centric approach is important, and ensuring that a patient is both motivated and empowered is critical to improving adherence/persistence. The COVID-19 pandemic has brought many changes to the way in which patients with NCDs are managed, with telemedicine and ehealth becoming more common. Changes have also occurred in the way in which patients can gain access to medications during the pandemic. The potential for these changes forms the basis of improving the management of patients with NCDs both during and after the pandemic. Over the coming months, a huge amount of work will be put into initiatives to promote adherence to COVID-19 vaccination programs. Those at highest risk of severe COVID-19, such as people aged 80 years and older, are likely to receive the vaccine first in some parts of world. Finally, social determinants of health are critical elements that can impact not just the likelihood of having an NCD or becoming infected with COVID-19, but also access to healthcare, and a patient’s adherence and persistence with their treatments.

The anatomy of the brain circulation is complex and variable.Autopsy studies and imaging techniques have detected anatomical variations of cerebral arteries (CAs) in 48–58% of the general population [1]. The duplication of the posterior cerebral artery (PCA) is a rare anatomic variant with a frequency of 2.3% [2, 3]. PCA duplication is characterised by the identification of a “true foetal” PCA, that originates from the internal carotid artery (ICA) and gives rise to the parieto-occipital artery, the internal occipital artery, the calcarine artery and the posterior pericallosal artery, associated with a PCA, that regularly arises from the basilar artery and gives rise to the posterior temporal artery [4].

The purpose of this retrospective study is to evaluate the prevalence and the imaging features of incidental intracranial aneurysms (IAs) in oncologic patients. We retrospectively examined 6599 brain CT studies performed for cancer staging (without and with intravenous iodinated contrast medium) at our institution, between January 2016 and December 2019. Subsequently, we selected only CT studies that revealed the presence of intracranial aneurysms as incidental findings; then, we recorded patients’ age and sex, primary tumour location and intracranial aneurysms position and size. Finally, the prevalence of intracranial aneurysms in this oncologic population was calculated. We found 60 intracranial aneurysms in 53 patients with a prevalence of 0.9%. There were 18 women and 35 men with a mean age of 67 years. Patients older than 65 years represented 64% of our study population. Aneurysm dimensions ranged between 2 and 43 mm, there was a giant aneurysm and 80% of aneurysms were smaller than 10 mm. The main localization was the right middle cerebral artery followed by the anterior communicating artery. Moreover, we observed mirror aneurysms originating from the middle cerebral arteries in three patients and from the carotid-ophthalmic artery junctions in one patient. The recent diffusion and better performance of imaging techniques led us to easier recognition of incidental intracranial aneurysms during brain CT examinations performed for cancer staging. Early detection of these vascular lesions allows for immediate radiologic evaluation and may improve patient management.

The COVID-19 pandemic will require health systems to test interventions to improve the recovery and social integration of adult survivors of COVID-19. Peer support is a complex intervention that allows COVID-19 survivors to give and receive practical and emotional support in relationship with other survivors of acute illness. The growing expertise within CAIRO can be leveraged by stakeholders interested in starting and sustaining a peer support program for COVID-19 survivors.

Background Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions Access of CSHCN to an ED is not infrequent. For this reason, it is fundamental for pediatricians working in any kind of ED to increase their general knowledge about CHSCN and to gain expertise in the management of such patients and their related medical complexity.

Noncommunicable diseases (NCDs) are the leading causes of mortality and morbidity across the world and factors influencing global poverty and slowing economic development. We summarize how the potential power of real-world data (RWD) and real-world evidence (RWE) can be harnessed to help address the disease burden of NCDs at global, national, regional and local levels. RWE is essential to understand the epidemiology of NCDs, quantify NCD burdens, assist with the early detection of vulnerable populations at high risk of NCDs by identifying the most influential risk factors, and evaluate the effectiveness and cost-benefits of treatments, programs, and public policies for NCDs. To realize the potential power of RWD and RWE, challenges related to data integration, access, interoperability, standardization of analytical methods, quality control, security, privacy protection, and ethical standards for data use must be addressed. Finally, partnerships between academic centers, governments, pharmaceutical companies, and other stakeholders aimed at improving the utilization of RWE can have a substantial beneficial impact in preventing and managing NCDs.

Background Chronic subdural hematoma associated with dural calcifications in previously pediatric shunted patients is a rare condition. The inner dural membrane opening can lead to progressive brain herniation into the subdural space due to brain reexpansion. Case Description A 15-year-old boy, previously shunted at birth for congenital hydrocephalus, presented with a giant chronic right hemispheric subdural hematoma. After 2 surgical procedures in which the subdural calcified neomembrane was opened and a subdural shunt was implanted, he developed a cortical brain herniation into the subdural space, resulting in brain ischemia and upper limb weakness and vomiting. The final surgical treatment consisted of an extensive wide peeling of visceral calcified membrane mutually to programmable valve placement along the subduroperitoneal shunt, in order to create a positive gradient between the subdural space and the ventricles. The patient experienced a prompt clinical improvement. Conclusions This case illustrates a rare complication of the treatment of a chronic subdural hematoma caused by insufficient opening of the calcified inner mambrane of the hematoma and encouraged by gradient pressure between the ventricular and subdural compartments. To avoid this complication, it is preferable to not open a thick, calcified, unelastic inner membrane. However, in case of lack of clinical and radiologic improvement, it may become necessary to open it: a wide opening should be attempted, in order to prevent brain strangulation.

Neuroendoscopic biopsy represents the procedure of choice for pure intraventricular lesions. Instead, in case of deep-seated paraventricular tumors, with intact ependyma, the advantage of neuroendoscopy over stereotactic biopsy is not so evident, because the lesion is not under direct vision; the tissue sample may be limited to more superficial ependymal layer, and bleeding may obscurate vision. Also, stereotactic biopsy may reserve additional problems for these lesions: inaccuracy caused by leak of cerebrospinal fluid and increased risk of severe hemorrhage due to damage of the ependymal vessels. We report two cases of young children affected by thalamic tumors that were biopsied using a modification of a recently proposed technique: endoscopic visual control, neuronavigated needle biopsy. This technique may combine the accuracy of a stereotactic needle biopsy with the advantage of visual control on site of ependymal puncture and possibility of immediate bleeding control.

Introduction: Hydrocephalus is not usually part of Down syndrome (DS). Fourth ventricle outlet obstruction is a rare cause of obstructive hydrocephalus, difficult to diagnose, because tetraventricular dilatation may suggest a communicant/nonobstructive hydrocephalus. Case Presentation: We describe the case of a 6-year-old boy with obstructive tetraventricular hydrocephalus, caused by Luschka and Magen­die foramina obstruction and diverticular enlargement of Luschka foramina (the so-called fourth ventricle outlet obstruction) associated with DS. He was treated with endoscopic third ventriculostomy (ETV) without complications, and a follow-up MRI revealed reduction of the ventricles, disappearance of the diverticula, and patency of the ventriculostomy. Conclusion: Diverticular enlargement of Luschka foramina is an important radiological finding for obstructive tetraventricular hydrocephalus. ETV is a viable option in tetraventricular obstructive hydrocephalus in DS.

The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society’s journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.

BACKGROUND Cavum trigeminale cephaloceles (CTCs) are characterized by a cystic appearance and extension of the posterolateral aspect of Meckel’s cave into the superomedial portion of the petrous apex. A possible mechanism is a transient or sustained increase of intracranial pressure transmitted to Meckel’s cave, leading to its secondary herniation, in the presence of predisposing local factors. The majority of CTCs are incidental findings. Among symptomatic cases, headache, trigeminal neuralgia, cerebrospinal fluid leak, vertigo, ataxia, facial numbness, hearing loss, diplopia, and other visual disturbances have been described. OBSERVATIONS The authors describe a case of an 18-month-old male patient referred to their hospital with drowsiness, vomiting, left cranial nerve VI palsy, and papilledema. Neuroradiological investigation revealed the presence of a CTC with a swollen aspect of the left pontine hemisection and indirect signs of intracranial hypertension. The patient was managed with implantation of a ventriculoperitoneal shunt. LESSONS CTCs are rare lesions that are difficult to recognize on neuroimaging, in which they can be mistaken for tumoral or inflammatory lesions. The most frequent asymptomatic forms should be considered as “leave-me-alone” lesions. In cases of intracranial hypertension, according to a supposed theory on the origin of CTCs, the authors recommend treating only the intracranial hypertension instead of performing more invasive surgical procedures, especially in pediatric patients.

Objective To generate real‐world evidence (RWE) from the United States to assess the impact of pill burden and the importance of achieving a stable daily dose of sertraline (time taken, number of dose adjustments needed) on adherence/persistence and healthcare resource utilisation (HCRU). Methods Retrospective analysis of the PharMetrics® Plus database (1 October 2012 to 31 March 2020) in the United States. Eligible patients had major depressive disorder (MDD) or obsessive‐compulsive disorder (OCD) and ≥1 claim for sertraline during index period (1 April 2013 to 31 March 2019, allowing 6‐months prior, 1‐year post‐index follow‐up). Patients who achieved stable daily dose of sertraline (>90 days on same dose) were categorised into five cohorts, depending on pill burden/daily dose: Cohort (1): 1 × 50 mg/d; Cohort (2): 1 × 100 mg/d; Cohort (3): 2 × 50 mg/d; Cohort (4): 1.5 × 100 mg/d; Cohort (5): 3 × 50 mg/d. Impact of pill burden on adherence/persistence and HCRU was assessed among cohorts using logistic regression analysis, and between patients who did vs did not stabilise on therapy. P

IMPORTANCEAs the United States continues to accumulate COVID-19 cases and deaths, and disparities persist, defining the impact of risk factors for poor outcomes across patient groups is imperative.OBJECTIVEOur objective is to use real-world healthcare data to quantify the impact of demographic, clinical, and social determinants associated with adverse COVID-19 outcomes, to identify high-risk scenarios and dynamics of risk among racial and ethnic groups.DESIGNA retrospective cohort of COVID-19 patients diagnosed between March 1 and August 20, 2020. Fully adjusted logistical regression models for hospitalization, severe disease and mortality outcomes across 1-the entire cohort and 2-within self-reported race/ethnicity groups.SETTINGThree sites of the NewYork-Presbyterian health care system serving all boroughs of New York City. Data was obtained through automated data abstraction from electronic medical records.PARTICIPANTSDuring the study timeframe, 110,498 individuals were tested for SARS-CoV-2 in the NewYork-Presbyterian health care system; 11,930 patients were confirmed for COVID-19 by RT-PCR or covid-19 clinical diagnosis.MAIN OUTCOMES AND MEASURESThe predictors of interest were patient race/ethnicity, and covariates included demographics, comorbidities, and census tract neighborhood socio-economic status. The outcomes of interest were COVID-19 hospitalization, severe disease, and death.RESULTSOf confirmed COVID-19 patients, 4,895 were hospitalized, 1,070 developed severe disease and 1,654 suffered COVID-19 related death. Clinical factors had stronger impacts than social determinants and several showed race-group specificities, which varied among outcomes. The most significant factors in our all-patients models included: age over 80 (OR=5.78, p= 2.29×10−24) and hypertension (OR=1.89, p=1.26×10−10) having the highest impact on hospitalization, while Type 2 Diabetes was associated with all three outcomes (hospitalization: OR=1.48, p=1.39×10−04; severe disease: OR=1.46, p=4.47×10−09; mortality: OR=1.27, p=0.001). In race-specific models, COPD increased risk of hospitalization only in Non-Hispanics (NH)-Whites (OR=2.70, p=0.009). Obesity (BMI 30+) showed race-specific risk with severe disease NH-Whites (OR=1.48, p=0.038) and NH-Blacks (OR=1.77, p=0.025). For mortality, Cancer was the only risk factor in Hispanics (OR=1.97, p=0.043), and heart failure was only a risk in NH-Asians (OR=2.62, p=0.001).CONCLUSIONS AND RELEVANCEComorbidities were more influential on COVID-19 outcomes than social determinants, suggesting clinical factors are more predictive of adverse trajectory than social factors.KEY POINTSQUESTIONWhat is the impact of patient self-reported race, ethnicity, socioeconomic status, and clinical profile on COVID-19 hospitalizations, severity, and mortality?FINDINGSIn patients diagnosed with COVID-19, being over 50 years of age, having type 2 diabetes and hypertension were the most important risk factors for hospitalization and severe outcomes regardless of patient race or socioeconomic status.MEANINGIn this large sample pf patients diagnosed with COVID-19 in New York City, we found that clinical comorbidity, more so than social determinants of health, was associated with important patient outcomes.

In this video, the authors present an interhemispheric transcallosal transchoroidal approach to a pineal mass in a 15-year-old boy. He received emergency endoscopic third ventriculostomy (ETV), then an endoscopic biopsy that revealed an immature teratoma. Surgical removal was selected. The mass was located very high in the posterior third ventricle, hidden behind the splenium of the corpus callosum and the vein of Galen, so an interhemispheric transcallosal approach followed by a complete dissection of the whole choroidal fissure was chosen and allowed complete removal of the tumor. Microsurgical dissection is presented, showing clearly in detail all the neurovascular structures encountered. The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2126.

The authors present a pediatric case of a pineoblastoma treated with gross-total removal through an occipital interhemispheric transtentorial approach (OITA). The child presented with acute hydrocephalus that was treated by endoscopic third ventriculostomy (ETV) and tumor biopsy through a single burr hole. Histology revealed a pineoblastoma. Microsurgical total removal was performed 3 months after neoadjuvant chemotherapy. OITA was chosen on the basis of the tumor’s location below the Herophilus-Galen line of sight. In this video, the authors show the positioning, the operating devices, the approach, and the microsurgical dissection, indicating all the neurovascular structures encountered. The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2122.

Desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIG) usually present with a large size, large cystic component, large dural implant, encasement of big vessels, clinical presentation within 18 months of life, high incidence of seizures and overall good prognosis, even if tumour surgery can be very challenging at first procedure. We retrospectively reviewed clinical and radiological data of patients diagnosed with desmoplastic infantile tumours who were surgically treated between 2008 and 2019. The series included 12 patients. The median age at surgery was 91 days. The average tumour volume was 212 cm3. Cystic components were predominant ranging from 0 to 295 cm3. Active hydrocephalus was pre-operatively evident in 5 cases. Eight patients (66.6%) received total or subtotal removal, three of them (25%) underwent partial removal, and one patient (8.3%) received a biopsy. One patient died within 24 h after surgery due to severe hypotension, as a consequence of significant intraoperative blood loss. Overall, seven (58.3%) patients were reoperated on the tumour after the first procedure: 4 patients were operated twice; 3 patients were operated 3 times. Two patients presented remote localizations and underwent chemotherapy. At last follow-up, 7 patients were tumour-free, 2 are alive with stable disease, and 2 are alive with progressive disease (leptomeningeal seeding). Desmoplastic infantile tumours are rare giant neonatal tumours. Total removal is the goal of treatment, but prognosis remains good even if total removal is not achieved. In case of tumour progression or epilepsy from residual tumour, reoperation is the first option, with chemotherapy reserved to unresectable or disseminated cases with mixed results, while, to date, radiotherapy still plays no role.

Thoracic paravertebral masses are a diagnostic challenge due to the broad spectrum of lesions that may be found in this compartment. The correct radiological approach is essential to narrow the differential diagnoses but, due to the overlap of imaging features of certain lesions, in selected cases, a pathological study may be necessary.

Identity diffusion is a core element of the borderline personality organization. A valid and reliable assessment tool is needed to identify at-risk adolescents in the Italian context. In this study...

Background: The variety of symptoms and radiological findings in patients with Chiari malformation type I makes both the indication for surgery and the technical modality controversial. We report our 5-year experience, describing our technique and critically evaluating the clinical results. Methods: Between 2012 and 2016, 25 patients (15 female and 10 male; mean age 39.2 years) underwent posterior fossa decompression for Chiari malformation type I. Their clinical complaints included headache, nuchalgia, upper limb weakness or numbness, instability, dizziness and diplopia. Syringomyelia was present in 12 patients (48%). Suboccipital craniectomy was completed in all cases with C1 laminectomy and shrinkage of the cerebellar tonsils by bipolar coagulation; duraplasty was performed with a suturable dura substitute. Results: Gratifying results were observed in our series. Symptoms and signs were resolved in 52% of patients, and 20% of patients had an improvement in their preoperative deficits. The symptoms of six patients (24%) were essentially unchanged, and one patient (4%) deteriorated despite undergoing surgery. Generally, patients with syringomyelia on magnetic resonance imaging (MRI) showed less symptomatic improvement after surgery. The syrinx disappeared in seven of 12 patients, and complications occurred in three patients (12%). Conclusion: Cerebellar tonsil reduction and restoration of cerebrospinal fluid (CSF) circulation provided clinical improvement and a stable reduction in the syrinx size in the vast majority of treated patients, with a low rate of complications.

Background Transcatheter valve-in-valve implantation (TViV) and minimally invasive reoperative aortic valve replacement (MIrAVR) have rapidly increased as alternatives to conventional reoperative surgical AVR. This study reports a single-center experience of patients undergoing TViV and MIrAVR after bioprosthetic valve failure. Methods In this retrospective review between March 2009 and October 2018, 68 patients without reoperative full sternotomies, concomitant procedures, active endocarditis, and prior homografts or coronary artery bypass grafting underwent isolated AVR for degenerated aortic bioprostheses. Society of Thoracic Surgeons (STS) risk scores and age are reported as median (interquartile range [IQR]) and length of stay is reported as mean (standard deviation [SD]) due to their characteristics of the distribution. Results Forty-one (60.3%) patients underwent TViV, and 27 (39.7%) patients underwent MIrAVR. Median [IQR] STS risk scores were 5.7 [4.0-7.8] and 2.0 [1.5-3.4] for TViV and MIrAVR, respectively (p ≤ .001). The median [IQR] age for TViV patients was higher (78 [71-84] vs. 66 [53-72] years, p ≤ 0.001). More permanent pacemakers were implanted (22.2% vs. 9.8%) following MIrAVR. The MIrAVR group had a higher rate of atrial fibrillation (18.5% vs. 9.8%, p = .466). Average (SD) length of stay was less in TViV (5.3 days, SD: 3.4 vs. 8.6 days, SD: 7.4, p = .001). Survival at 1 year was not significantly different for TViV and MIrAVR (94.9% [95% confidence interval [CI]: 81.0%, 98.7%] and 86.9% [95% CI: 64.0%, 95.7%], respectively [p = .969]). Conclusions Despite being at higher-risk, patients undergoing TViV had reduced rates of permanent pacemaker implantations and atrial fibrillation, and a shorter hospital stay as compared to MIrAVR. Survival at 1-year was similar between the two groups.

While immune responses have been rigorously examined after intravenous Listeria monocytogenes (Lm) infection, less is understood about its dissemination from the intestines or the induction of adaptive immunity after more physiologic models of foodborne infection. Consequently, this study focused on early events in the intestinal mucosa and draining mesenteric lymph nodes (MLN) using foodborne infection of mice with Lm modified to invade murine intestinal epithelium (InlAM Lm). InlAM Lm trafficked intracellularly from the intestines to the MLN and were associated with Batf3-independent dendritic cells (DC) in the lymphatics. Consistent with this, InlAM Lm initially disseminated from the gut to the MLN normally in Batf3–/– mice. Activated migratory DC accumulated in the MLN by 3 days post-infection and surrounded foci of InlAM Lm. At this time Batf3–/– mice displayed reduced InlAM Lm burdens, implicating cDC1 in maximal bacterial accumulation in the MLN. Batf3–/– mice also exhibited profound defects in the induction and gut-homing of InlAM Lm-specific effector CD8 T cells. Restoration of pathogen burden did not rescue antigen-specific CD8 T cell responses in Batf3–/– mice, indicating a critical role for Batf3 in generating anti-InlAM Lm immunity following foodborne infection. Collectively, these data suggest that DC play diverse, dynamic roles in the early events following foodborne InlAM Lm infection and in driving the establishment of intestinal Lm-specific effector T cells. Fil: Imperato, Jessica Nancy. Stony Brook University Renaissance School Of Medicine; Estados Unidos Fil: Xu, Daqi. Uconn Health; Estados Unidos Fil: Romagnoli, Pablo Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa | Universidad Nacional de Cordoba. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa | Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa.; Argentina Fil: Qiu, Zhijuan. Stony Brook University Renaissance School Of Medicine; Estados Unidos Fil: Perez, Pedro. Stony Brook University Renaissance School Of Medicine; Estados Unidos Fil: Khairallah, Camille. Stony Brook University Renaissance School Of Medicine; Estados Unidos Fil: Pham, Quynh Mai. Uconn Health; Estados Unidos Fil: Andrusaite, Anna. University of Glasgow; Reino Unido Fil: Bravo Blas, Alberto. The Beatson Institute For Cancer Research; Reino Unido Fil: Milling, Simon W. F.. University of Glasgow; Reino Unido Fil: Lefrancois, Leo. Uconn Health; Estados Unidos Fil: Khanna, Kamal M.. University of New York; Estados Unidos Fil: Puddington, Lynn. Uconn Health; Estados Unidos Fil: Sheridan, Brian S.. Stony Brook University Renaissance School Of Medicine; Estados Unidos

A method to determine T-2 and HT-2 toxins, both in feed and food, is described. The method is based on sample clean-up by immunoaffinity columns, followed by triple quadrupole LC-MS/MS determination. It was in-house validated in compliance with the European Union legislation, in the concentration range 5.0-750 µg kg-1 and accredited according to the ISO/IEC 17025 standard, for the scope of official control of feed and food. The method was applied to monitor the contamination levels of T-2 and HT-2 toxins in 105 feed samples, both raw materials and compound feed and 17 cereals and derived products for human consumption, collected in Southern Italy between 2015 and 2019. T-2 toxin was quantified in 32 feed (30.5%) and in 2 food samples (11.8%). HT-2 toxin was quantified in 65 feed (61.9%) and in 3 food (17.6%) samples.

The objective of this review was to understand the clinical utilization, utility, and variability in the usage of adjunctive hyperbaric oxygen therapy (HBOT). Surgical site infection is associated with high morbidity and mortality, increased health care expenditure, and decreased quality of life. With the increasing prevalence of adult spinal deformity and spinal fusion surgery, it is imperative to understand the potential benefits of adjunctive treatments. HBOT is a safe and common procedure indicated to treat various medical conditions. We conducted a literature search across 3 databases for English articles published between December 1, 2019 and December 1, 2000. Thirteen studies were included. HBOT may lessen the duration of antimicrobial therapy and mitigate instrument removal and revision surgery. The current usage indications for HBOT are supported by level III evidence for chronic osteomyelitis and level IV evidence for osteoradionecrosis. However, the same level of evidence exists to support the beneficial use of adjunctive HBOT for noncomplicated spinal infections within 2 months after surgery. When cultured, the most common organisms were Staphylococcus aureus and other low-virulence organisms. The most common treatment protocol consists of 90-minute sessions of 100% Fio2 at 2-3 atmosphere absolute with a mean of 35.3 ± 11.6 sessions for 5.2 ± 1.4 weeks. Adjunctive HBOT should be considered in select high-risk patients. Further improvements in diagnosis and categorization of spinal infections are necessary and will indelibly aid the decision making for the initiation of HBOT.

Pediatric spinal epidural abscess is a major suppurative infection of the central nervous system. It is an extremely rare pathology carrying serious risk of permanent neurological sequelae if is not properly treated. All the pertinent literature was analyzed, focused on pediatric cases of spinal epidural abscess and its peculiar features. Two illustrative cases are also presented. The first case is that of a 9-year old girl who took medical attention, when she was already paraplegic. Despite prompt surgical evacuation and good neuroradiological outcome and intensive rehabilitation, motor deficits did not recover after surgery. The second case was that of a 14-year old girl who presented with fever, neck pain, and torticollis. Prompt diagnosis, decompressive surgery, and 6 weeks of antibiotics allowed good neurological outcome. The management of spinal epidural abscess includes evacuation of the abscess with decompression of the spinal cord and prolonged antibiotic treatment. The presence of neurological deficit and the delay in the initiation of proper treatment are the two factors that more worsen prognosis.

The DNA repair enzyme AAG has been shown in mice to promote tissue necrosis in response to ischaemic reperfusion or treatment with alkylating agents. A chemical probe inhibitor is required for investigations of the biological mechanism causing this phenomenon and as a lead for drugs that are potentially protective against tissue damage from organ failure and transplantation, and alkylative chemotherapy. Herein, we describe the rationale behind the choice of arylmethylpyrrolidines as appropriate aza-nucleoside mimics for an inhibitor followed by their synthesis and the first use of a microplate-based assay for quantification of their inhibition of AAG. We finally report the discovery of an imidazol-4-ylmethylpyrrolidine as a fragment-sized, weak inhibitor of AAG.

Background Electrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation. Methods Here, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and measured serum cytokine levels in healthy mice. Results Surprisingly, we found that specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the pro-inflammatory cytokine tumor necrosis factor (TNF), while other parameters selectively lowered serum TNF levels, as compared to sham-stimulated mice. In addition, serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) were significantly increased by select parameters of electrical stimulation but remained unchanged with others. Conclusions These results indicate that electrical stimulation parameter selection is critically important for the modulation of cytokines via the cervical vagus nerve and that specific cytokines can be increased by electrical stimulation in the absence of inflammation. As the next generation of bioelectronic therapies and devices are developed to capitalize on the neural regulation of inflammation, the selection of nerve stimulation parameters will be a critically important variable for achieving cytokine-specific changes.

Electrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation. Here, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and measured serum cytokine levels in healthy mice. Surprisingly, we found that specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα), while other parameters selectively lowered serum TNFα levels, as compared to sham-stimulated mice. In addition, serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) were significantly increased by select parameters of electrical stimulation but remained unchanged with others. These results indicate that electrical stimulation parameter selection is critically important for the modulation of cytokines via the cervical vagus nerve and that specific cytokines can be increased by electrical stimulation in the absence of inflammation. As the next generation of bioelectronic therapies and devices are developed to capitalize on the neural regulation of inflammation, the selection of nerve stimulation parameters will be a critically important variable for achieving cytokine-specific changes.

46,XY individuals with 5α-reductase-2 deficiency syndrome have ambiguous genitalia with a clitoral-like phallus, severely bifid scrotum, and pseudovaginal perineoscrotal hypospadias. As a result of this genital ambiguity, many are thought to be girls at birth and are treated as such from the time they are born. However, at puberty virilization occurs, whereupon affected individuals, with few exceptions, reveal their male gender identity and assume a male gender role. Much of the research on gender identity of individuals with 5α-reductase-2 deficiency was derived from a study of 38 males in three rural villages in the Dominican Republic. This chapter describes the clinical, biochemical, and genetic features of the syndrome; considers the impact of androgens on gender identity and gender role; and outlines treatment considerations.

Acute myeloid leukemia (AML) is a highly heterogeneous cancer associated with different patterns of gene expression determined by the nature of their DNA mutations. These mutations mostly act to deregulate gene expression by various mechanisms at the level of the nucleus. By performing genome-wide epigenetic profiling of cis-regulatory elements, we found that AML encompasses different mutation-specific subclasses associated with the rewiring of the gene regulatory networks that drive differentiation into different directions away from normal myeloid development. By integrating epigenetic profiles with gene expression and chromatin conformation data, we defined pathways within gene regulation networks that were differentially rewired within each mutation-specific subclass of AML. This analysis revealed 2 major classes of AML: one class defined by mutations in signaling molecules that activate AP-1 via the mitogen-activated protein (MAP) kinase pathway and a second class defined by mutations within genes encoding transcription factors such as RUNX1/CBFβ and C/EBPα. By identifying specific DNA motifs protected from DNase I digestion at cis-regulatory elements, we were able to infer candidate transcription factors bound to these motifs. These integrated analyses allowed the identification of AML subtype-specific core regulatory networks that are required for AML development and maintenance, which could now be targeted in personalized therapies.

Maximal safe resection represents the gold standard for surgery of malignant brain tumors. As regards gross-total resection, accurate localization and precise delineation of the tumor margins are required. Intraoperative diagnostic imaging (Intra-Operative Magnetic Resonance-IOMR, Intra-Operative Computed Tomography-IOCT, Intra-Operative Ultrasound-IOUS) and dyes (fluorescence) have become relevant in brain tumor surgery, allowing for a more radical and safer tumor resection. IOUS guidance for brain tumor surgery is accurate in distinguishing tumor from normal parenchyma, and it allows a real-time intraoperative visualization. We aim to evaluate the role of IOUS in gliomas surgery and to outline specific strategies to maximize its efficacy. We performed a literature research through the Pubmed database by selecting each article which was focused on the use of IOUS in brain tumor surgery, and in particular in glioma surgery, published in the last 15 years (from 2003 to 2018). We selected 39 papers concerning the use of IOUS in brain tumor surgery, including gliomas. IOUS exerts a notable attraction due to its low cost, minimal interruption of the operational flow, and lack of radiation exposure. Our literature review shows that increasing the use of ultrasound in brain tumors allows more radical resections, thus giving rise to increases in survival.

High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA) is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX) is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS), on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB) areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO) but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients.

John P. Craig (1923-2016) was an eminent physician-scientist, gifted educator, and greatly valued mentor. Born in West Liberty, Ohio on 29 November 1923, he attended Oberlin College, and received his medical degree from Case Western Reserve University, School of Medicine. This was followed by an internship at Yale University Medical Center, and then service in the U.S. Army during the Korean War. He was a battalion surgeon, preventive medicine officer, and epidemiologist. While in Korea, he conducted important investigations of hemorrhagic fever among American troops. His observations led to the recognition of hemorrhagic fever with renal syndrome, now called Korean hemorrhagic fever. He also identified a new Hanta virus. Craig received his Master of Public Health degree magna cum laude from the Harvard School of Public Health. He then worked with Nobel Laureate, Max Theiler, at the Rockefeller Foundation. Soon afterwards, he joined the faculty of the Department of Microbiology and Immunology at the State University of New York, Downstate Medical Center, where he established a new research laboratory. Over the years, his research focused on diphtheria infections and cholera. He became internationally respected for his work on cholera, and specifically on cholera toxin and its relationship to vascular permeability. He served for over 6 years as the Chair of the Cholera Panel of the U.S.-Japan Cooperative Program, and in this position set the direction for future research. The author of over 100 articles published in the peer-reviewed scientific literature, he also gave numerous presentations at national and international scientific meetings on a wide range of microbial diseases. Craig was highly regarded by colleagues and students as a superb teacher. He was a leader in initiating patient-oriented problem-solving (POPS) exercises for medical students. He also led curricular reform in the medical school in the 1990s whose purpose was to reduce lecture hours and expand time for small-group interactive sessions. Craig was designated Distinguished Teaching Professor by the State University of New York, and inducted as an Honorary Alumnus of the College of Medicine. The John P. Craig Award for Excellence in Microbiology and Immunology was established in 1993, and is annually presented to a graduating medical student. Following retirement to Tucson, Arizona, Craig devoted time to planning and teaching a tropical medicine course in Costa Rica that was co-sponsored by the University of Costa Rica Medical School and Louisiana State University. He was a member of the Board of Managers of the Wright Nature Center in Trinidad, and an active volunteer in the Herpetology Department of the Arizona-Sonora Desert Museum in Tucson, Arizona. He also had a great interest in ornithology. John P. Craig passed away in Tucson, Arizona on 27 September 2016 in his ninety-third year. He was an eminent success as a research scientist as well as an outstanding educator and mentor. As a result, he had a lasting influence on the lives and careers of both students and colleagues.

Energy-based healing techniques have rarely been explored in current complementary therapies literature. This therapy is appropriate for cardiac nursing and can be implemented as part of nursing care. The authors investigated the acute effects of a standardised energy-based healing technique on cardiac autonomic regulation. Method: This study was conducted on 18 healthy students (15 female, three male), all non-smokers aged 18–35 years. Heart rate variability (HRV) was analysed 10 minutes before and 10 minutes after the energy-based healing technique was carried out. Geometric, time and frequency domain indices of HRV were examined. The subjects were blindfolded and sat at rest for 10 minutes, then received a standardised energy-based healing technique from an experienced male healer; they remained blindfolded and seated for a further 10 minutes. Results: Time and frequency domain indices of HRV were not significantly different before and after the energy-based healing technique. TINN (triangular interpolation histogram of RR intervals) (P=0.04) and RRTri (triangular index) (P=0.02) were increased after the therapy. A Poincaré plot indicated a slight increase in RR intervals dispersion after energy-based healing technique. Conclusion: A standardised energy-based healing technique marginally improved cardiac autonomic function in healthy subjects.

OBJECTIVE Neuroendoscopic removal of intraventricular tumors is difficult and time consuming because of the lack of an effective decompression system that can be used through the working channel of the endoscope. The authors report on the utilization of an endoscopic ultrasonic aspirator in the resection of intraventricular tumors. METHODS Twelve pediatric patients (10 male, 2 female), ages 1–15 years old, underwent surgery via a purely endoscopic approach using a Gaab rigid endoscope and endoscopic ultrasonic aspirator. Two patients presented with intraventricular metastases from high-grade tumors (medulloblastoma, atypical teratoid rhabdoid tumor), 2 with subependymal giant cell astrocytomas (associated with tuberous sclerosis), 2 with low-grade intraparaventricular tumors, 4 with suprasellar tumors (2 craniopharyngiomas and 2 optic pathway gliomas), and 2 with pineal tumors (1 immature teratoma, 1 pineal anlage tumor). Hydrocephalus was present in 5 cases. In all patients, the endoscopic trajectory and ventricular access were guided by electromagnetic neuronavigation. Nine patients underwent surgery via a precoronal bur hole while supine. In 2 cases, surgery was performed through a frontal bur hole at the level of the hairline. One patient underwent surgery via a posterior parietal approach to the trigone while in a lateral position. The endoscopic technique consisted of visualization of the tumor, ventricular washing to dilate the ventricles and to control bleeding, obtaining a tumor specimen with biopsy forceps, and ultrasonic aspiration of the tumor. Bleeding was controlled with irrigation, monopolar coagulation, and a thulium laser. RESULTS In 7 cases, the resection was total or near total (more than 90% of lesion removed). In 5 cases, the resection was partial. Histological evaluation of the collected material (withdrawn using biopsy forceps and aspirated with an ultrasonic aspirator) was diagnostic in all cases. The duration of surgery ranged from 30 to 120 minutes. One case was complicated by subdural hygroma requiring a subduro-peritoneal shunt implant. CONCLUSIONS In this preliminary series, endoscopic ultrasonic aspiration proved to be a safe and reliable method for achieving extensive decompression or complete removal in the management of intra- and/or paraventricular lesions in pediatric patients.

When pathogens and toxins breech the epithelial barrier, antigens are transported by the lymphatic system to lymph nodes. In previously immunized animals, antigens become trapped in the draining lymph nodes, but the underlying mechanism that controls antigen restriction is poorly understood. Here we describe the role of neurons in sensing and restricting antigen flow in lymph nodes. The antigen keyhole-limpet hemocyanin (KLH) injected into the mouse hind paw flows from the popliteal lymph node to the sciatic lymph node, continuing through the upper lymphatics to reach the systemic circulation. Re-exposure to KLH in previously immunized mice leads to decreased flow from the popliteal to the sciatic lymph node as compared with naïve mice. Administering bupivacaine into the lymph node region restores antigen flow in immunized animals. In contrast, neural activation using magnetic stimulation significantly decreases antigen trafficking in naïve animals as compared with sham controls. Ablating NaV1.8 + sensory neurons significantly reduces antigen restriction in immunized mice. Genetic deletion of FcγRI/FcεRI also reverses the antigen restriction. Colocalization of PGP9.5-expressing neurons, FcγRI receptors and labeled antigen occurs at the antigen challenge site. Together, these studies reveal that neuronal circuits modulate antigen trafficking through a pathway that requires NaV1.8 and FcγR.

Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory disease characterized by extensive joint tissue inflammation. Implantable bioelectronic devices targeting the inflammatory reflex reduce TNF production and inflammation in preclinical models of inflammatory disease, and in patients with RA and Crohn’s disease. Here, we assessed the effect of applying a vibrotactile device to the cymba concha of the external ear on inflammatory responses in healthy subjects, as well as its effect on disease activity in RA patients. Six healthy subjects received vibrotactile treatment at the cymba concha, and TNF production was analyzed at different time points post-stimulation. In a separate study, nineteen healthy subjects were enrolled in a randomized cross-over study, and effects of vibrotactile treatment at either the cymba concha or gastrocnemius on cytokine levels were assessed. In addition, the clinical efficacy of vibrotactile treatment on disease activity in RA was assessed in nine patients with RA in a prospective interventional study. Vibrotactile treatment at the cymba concha reduced TNF levels, and the suppressive effect persisted up to 24 h. In the cross-over study with 19 healthy subjects, vibrotactile treatment at the cymba concha but not at the gastrocnemius significantly reduced TNF, IL-1β, and IL-6 levels compared to pre-treatment baseline (TNF p

The Zika virus was first identified in 1947 in the Zika Forest of Uganda. It was discovered in a rhesus monkey that had been placed in a cage on a sentinel platform in the forest by the Virus Research Institute. When this writer visited the institute and the Zika Forest in 1961, work was underway to identify mosquito species at various levels of the tree canopy. This was done through the placement of traps at various levels of a 120-foot-high steel tower which this writer climbed. At that time, researchers isolated 12 strains of Zika virus from traps on the tower. Over the next six decades, the virus spread slowly to other parts of Africa, and eventually appeared in Southeast Asia, transmitted by Aedes aegypti and other Aedes mosquito species. By 1981, only 14 cases of illness had been reported as due to the Zika virus. Since most infections with this virus are either mild or asymptomatic, its true geographic spread was not fully appreciated. The current globalization of the Zika epidemic began on the Pacific island of Yap in the Federated States of Polynesia in 2007. This was the first known presence of the Zika virus outside of Africa and Southeast Asia. It was estimated that 73 % of the island's population had been infected. In 2013, the virus spread to French Polynesia where an estimated 28,000 cases occurred in a population of 270,000. During that year and afterwards, microcephaly and other congenital abnormalities were observed in the infants of women who were pregnant when they contracted the virus. It is currently not known if cases of microcephaly have resulted from infection of pregnant women or from infection plus some other co-factor. The epidemic rapidly spread to the Cook Islands and Easter Island. In 2015, Zika virus infection was diagnosed in Brazil where it was associated with microcephaly in the infants of some women who were pregnant when they contracted the disease. Cases of the Guillain-Barré syndrome were also found to be associated with Zika virus infection. How the disease entered Brazil is a matter of conjecture. However, the strain responsible for the epidemic in Brazil and elsewhere in South and Central America is phylogenetically identical to that which caused the epidemic in French Polynesia. The wide distribution of Aedes aegypti, a principal vector of the virus, and other Aedes species has greatly facilitated the spread of the disease. Aedes aegypti is an invasive species of mosquito in the Western Hemisphere that has adapted well to densely-populated urban environments. In addition, male-to-female human sexual transmission has increasingly been demonstrated in the US and elsewhere. In February 2016, the World Health Organization (WHO) declared the current Zika outbreak a Public Health Emergency of international concern. On the recommendation of its Emergency Committee on Zika Virus and Observed Increase in Neurological Disorders and Neonatal Malformations, WHO issued a group of recommendations to contain the epidemic. The globalization of the Zika virus was made possible by the widespread presence in various parts of the world of Aedes vectors and increased human travel that facilitated geographic spread. This globalization of Zika follows upon that of West Nile, Ebola, Dengue, and Chikungunya. Its ultimate spread is difficult to predict, but will hopefully be restricted through vigorous preventive measures.

Global health electives based in resource-poor countries have become extremely popular with medical students from resource rich ones. As the number of such programs and participants increase, so too do the absolute health and safety risks. It is clear from a number of published reports that many institutions provide little or no meaningful preparedness for students and do little to ensure their health and safety. These deficiencies together can affect students, their foreign hosts, and sponsoring institutions. The School of Public Health at the State University of New York, Downstate Medical Center, and its predecessor, the Department of Preventive Medicine and Community Health, have sponsored a 6-8 week global health elective for fourth year medical students since 1980. The purposes of this elective are to provide students with an opportunity to observe the health care and public health systems in resource-poor countries, provide medical service, and have a cross-cultural experience. Over the course of the past 35 years, 386 students have participated in this global health elective in more than 41 resource-poor countries. Recent annual applications for this elective have been as high as 44 out of a class of 200 students. Over the past 10 years, annual acceptance rates have varied, ranging from a low of 32 % in 2007-2008 to a high of 74 % in 2010-2011 and 2013-2014. Careful screening, including a written application, review of academic records and personal interviews, has resulted in the selection of highly mature, adaptable, and dedicated students who have performed well at overseas sites. Appropriately preparing students for an overseas global health experience in resource-poor countries requires the investment of much professional and staff time and effort. At the SUNY Downstate School of Public Health, these resources have underpinned our Global Health in Developing Countries elective for many years. As a result, the elective is characterized by meticulous organization, extensive preparedness measures for students, and continuous monitoring of site and country safety. The health of students is ensured by one-on-one assessment of immunization needs, anti-malarials, and the provision of a five-day supply of post-exposure HIV prophylaxis. Students sign agreements regarding the legal issues, immunizations, and anti-malarials recommended as well as HIV post-exposure prophylaxis. They are also required to obtain medical evacuation insurance provided by the university, and medical care insurance valid overseas. Student travel plans are also approved as is in-country lodging. The focus of our 6-8 week global health elective is not clinical medicine. Rather, it is to enable students to learn about the health care and public health systems in a resource-poor country. Through that focus, they also come to understand the causes of health and health care disparities that exist in the country to which they are assigned. Our students are greatly advantaged with regard to cross-cultural understanding since our school is located in New York City's Borough of Brooklyn, where 40 % of the population was born outside of the U.S. Our comprehensive effort at risk management for this global health elective includes a thorough debriefing for each student upon his/her return. Special attention is given to ascertaining illness or injury while overseas, and, when necessary, immediate referral is made to an appropriate university clinical department where a student can be appropriately case managed. Meticulous oversight, careful selection of safe overseas sites, and attention to preparing students have resulted in significant risk reduction and successful experiences for the majority of our 386 students. This article describes the model we have developed for ensuring the health, safety, and preparedness of students participating in our global health elective.