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Background: Obesity disproportionately affects marginalized and low-income populations. Birth parent obesity from the prenatal period and childhood has been associated with child obesity. It is unknown whether prenatal or postnatal birth parent obesity has differential effects on subsequent changes in adiposity and metabolic health in children. Objectives: We evaluated how birth parent obesity 7 y after delivery was associated with child body composition changes and cardiometabolic health in midchildhood and further assessed the influence of the perinatal and postpartum period on associations. Methods: Black and Dominican pregnant individuals were enrolled, and dyads (n = 319) were followed up at child age 7 and 9 y. Measures included, height, weight, waist circumference (WC), and percent body fat (BF%). Multiple linear regression was used to relate postpartum weight status with child outcomes accounting for attrition, and a series of secondary analyses were conducted with additional adjustment for perinatal weight status, gestational weight gain (GWG), and/or long-term weight retention to evaluate how these factors influenced associations. Results: Almost one-quarter (23%) of birth parents and 24.1% children were classified with obesity at child age 7 y, while at 9 y, 30% of children had obesity. Birth parent obesity at child age 7 y was associated with greater changes, from ages 7 to 9 y, in child BMI z-score (β: 0.13; 95% CI: 0.02, 0.24) and BF% (β: 1.15; 95% CI: 0.22, 2.09) but not obesity at age 9 y. All observed associations crossed the null after additional adjustment for prenatal factors. Conclusions: Birth parent obesity at 7-y postpartum is associated with greater gains in child BMI z-score and BF% in midchildhood. These associations diminish after accounting for prenatal size, suggesting a lasting impact of the perinatal environment and that interventions supporting families from the prenatal period through childhood are needed.

ObjectiveA mother-child dyad trajectory model of weight and body composition spanning from conception to adolescence was developed to understand how early life exposures shape childhood body composition.MethodsAfrican American (49.3%) and Dominican (50.7%) pregnant mothers (n = 337) were enrolled during pregnancy, and their children (47.5% female) were followed from ages 5 to 14. Gestational weight gain (GWG) was abstracted from medical records. Child weight, height, percentage body fat, and waist circumference were measured. GWG and child body composition trajectories were jointly modeled with a flexible latent class model with a class membership component that included prepregnancy BMI.ResultsFour prenatal and child body composition trajectory patterns were identified, and sex-specific patterns were observed for the joint GWG-postnatal body composition trajectories with more distinct patterns among girls but not boys. Girls of mothers with high GWG across gestation had the highest BMI z score, waist circumference, and percentage body fat trajectories from ages 5 to 14; however, boys in this high GWG group did not show similar growth patterns.ConclusionsJointly modeled prenatal weight and child body composition trajectories showed sex-specific patterns. Growth patterns from childhood though early adolescence appeared to be more profoundly affected by higher GWG patterns in females, suggesting sex differences in developmental programming.

Climate change imposes physiological constraints on organisms particularly through changing thermoregulatory requirements. Bergmann's and Allen's rules suggest that body size and the size of thermoregulatory structures differ between warm and cold locations, where body size decreases with temperature and thermoregulatory structures increase. However, phenotypic plastic responses to malnutrition during development can result in the same patterns while lacking fitness benefits. The Gulf of Maine (GOM), located at the southern end of the Labrador current, is warming faster than most of the world's oceans, and many of the marine species that occupy these waters exist at the southern edge of their distributions including Atlantic puffins (Fratercula arctica; hereafter "puffin"). Monitoring of puffins in the GOM, at Machias Seal Island (MSI), has continued annually since 1995. We asked whether changes in adult puffin body size and the proportional size of bill to body have changed with observed rapid ocean warming. We found that the size of fledgling puffins is negatively related to sea surface temperature anomalies (warm conditions = small fledgers), adult puffin size is related to fledgling size (small fledgers = small adults), and adult puffins have decreased in size in recent years in response to malnutrition during development. We found an increase in the proportional size of bill to wing chord, likely in response to some mix of malnutrition during development and increasing air temperatures. Although studies have assessed clinal variation in seabird morphology with temperature, this is the first study addressing changes in seabird morphology in relation to ocean warming. Our results suggest that puffins nesting in the GOM have morphological plasticity that may help them acclimate to ocean warming.

Background: Traditionally, it takes an average of 17 years for a research outcome to reach clinical practice. Similarly, the field of anatomy is not exception to that rule. This indicates there is a significant information gap between medical research and its finalized incorporation into patient care. Methods: A list of current anatomy textbooks and atlases are reviewed, and the breach between basic science and clinical research is investigated through the coverage of six specific topics. Results: This includes the parasympathetic innervation to the lacrimal gland, the oversimplification of the parasympathetic innervation to the ethmoid and sphenoid sinuses, clinical presentation of middle ear pathology (Ramsay Hunt Syndrome), as well as the presence of venous valves in the arch of the azygos and in the head and neck region. The progressive anatomical research findings are discussed while comparing information currently taught to medical students. Conclusion: The impact of the widening gap is considered through presentation of clinical implications where applicable. As the need for bridging this mismatch is immanent, means of feasible first steps are proposed.

Aim: The cadaver donor can be utilized for displaying anatomical structures, pathological processes, medical devices encountered and surgical intervention. In an integrative curriculum the cadaver donor serves as a vehiculum to facilitate discussion on a wide variety of topics. Methods: A case of a femoro-femoral bypass (FFB), with stents in the common and external iliac arteries in aortoiliac obstructive disease, is functioning as a model for integrating many of the basic science knowledge by showing the extent of arteriosclerosis and providing additional notes that can be used for stimulating discussion among medical students. Limitations: The provided set of notes should be interpreted as one of many examples that can be construed depending on for instance subjects to cover and level of difficulty when presenting this case. Conclusion: Donor cadavers have proven to be an indispensable resource for instructing anatomy to medical students and health care providers. Each one holds enigmas that a physician may have overlooked prior to death of the patient. This case shows a femoro-femoral bypass with multiple intra-arterial stents. Upon further investigation, extensive arteriosclerosis was found throughout most medium to large arteries, with stents and patches maintaining vascularization. Removal of the entire aorto-iliacfemoral arterial tree provided a rare and detailed view of this condition, available through 3D scanning and photogrammetry for future review. This case prompts further discussion towards aspects covered in an integrated system-based curriculum, and notes provided in the appendix serve as examples.

Purpose: With a relatively simple object such as a lanyard holding an ID badge the translational phenomenon of why it takes so long for inventions or knowledge to reach consumers or beneficiaries is investigated. Basic procedures: Two collections of ID badges with and without lanyards were obtained and categorized according to the type of conference or institution and the type of possible harm the user of the ID badge may be exposed to. Findings: Lanyards were investigated for the material they were made of, the manner in which they were attached to the ID badge and the type of possible harm they could cause. Of the four types of possible harm, Harmful (H), Harmful by Individual Choice (HIC), Not Harmful (NH) and Safe (S), only 16% can be considered safe because of breakaway latches provided. Harmful but by individual choice because of the addition of an alternative method, a safety pin, for attaching the ID badge was found in 15% of the samples. The safest method was only a safety pin or magnet for displaying the ID badge. Over a two-decade period, there was no sign of a trend to more safety regarding the display of the ID badge. Conclusions: Safety breakaway latches or other means of preventing harm when wearing an ID badge are not commonly supplied at conferences. The safety issue of lanyards worn around the neck at conferences has not shown improvement over the years. The manufacture of lanyards of a non-durable material that will tear when force is applied is a suggested option. Lanyards should have a minimum of three breakaway latches.

Purpose: How much do anatomical and histological texts inform medical students about the arterial supply to the skin? What is a good method in a system-based curriculum to highlight the importance of blood supply to the skin? Basic procedures: Anatomical and histological texts were sourced for the following keywords: skin graft, skin flap, septocutaneous vessel, musculocutaneous vessel, perforator, angiosome, perforasome, sural artery, saphenous artery, gastrocnemial artery. From the skin flaps available for functional and cosmetic reconstructive surgery three were chosen as a good example of blood supply to muscle/bone and overlying skin to be illustrative to medical students. Findings: Only few anatomical texts mention blood supply of the skin in some detail. Non demonstrate and link angiosomes to reconstructive surgical procedures.There are 3 skin flaps which are easy to dissect to demonstrate medical students the origin of the blood supply to the muscle (and bone) and the overlying tissues (skin). Pictures of these flaps show ease of procuring and detail for demonstration. Conclusions: Anatomical and histological texts have not incorporated published research findings from basic science investigators and clinicians about angiosomes. Through the use of prosections of three skin grafts the medical student can appreciate the blood supply to the skin and understand the underlying principle in reconstructive surgery.

Background: A cricothyroidotomy is a procedure which creates a laryngeal opening. Medical students are told that this procedure is without major complications and simple to perform; however, professionals who have witnessed a laryngotomy include considerable hemorrhage and issues locating the correct insertion site in procedure preparation. Various laryngeal devices were analyzed, and determination of superiority was based on ease and success of insertion. Methods: Our study was limited to 30 healthcare professional volunteers and 3 devices: a scalpel, steak knife, and percutaneous cricothyroidotomy key-ring device (PCKD). Their task was to perform a laryngotomy within a set time period on a cadaver. ‘Success or failure’ was determined through dissection at a later date. Result: Among 30 volunteers, 21 successfully accessed the larynx. Success was highest with the steak knife and lowest with the PCKD, revealing device familiarity may be influential. Participants with previous clinical experience also had higher success, indicating practical experience may play a role in addition to anatomical knowledge. Conclusion: Cricothyroidotomy is a procedure mentioned in medical school, where theoretical knowledge is readily taught. Yet those who are deemed familiar with the anatomy is not reassuring. This presses the importance of medical curriculums implementing practical training, while simultaneously teaching the underlying anatomy and physiology. Trial registration: This study was approved by the St. George's University IRB, No. 06014. Keywords: Laryngotomy, Cricothyroidotomy, Emergency airway management, Medical education

BackgroundParkinson's disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk.MethodsIn June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD.ResultsWe describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs.ConclusionsPD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.

Rubinstein-Taybi syndrome (RTS) is a rare genetic developmental disorder that often shows associated language delay. However, literature on language development in RTS is very limited, particularly for the period of early communicative development, when standardized testing can be minimally informative. The purpose of the current study was to present a descriptive profile of the intentional communicative acts of a 4-year-old child with RTS, both to add to the literature on the syndrome, and as an example of non-standard profiling of early communication. The child was video-recorded in a natural context with familiar conversational partners. Analyses of the videotaped interactions included rate of communication, communicative functions and modes, and discourse patterns in terms of initiation and response. The child's mean rate of communication was 6 communicative acts per minute. In terms of communicative function, assertive (commenting) communicative acts were most common, followed by directive (requests) and expressive (affective) acts. Mode of communication was less advanced than communicative function; vocalizations were the most frequent mode, although linguistic skills were emerging (signs, single words). Implications for treatment are suggested for children with development delays on the threshold between prelinguistic and one-word phases of development. (Contains 5 tables and 3 footnotes.)

Following intraparenchymal injection of the dopamine (DA) neurotoxin 6-hydroxydopamine, we previously demonstrated passage of fluoresceinisothiocyanate-labeled albumin (FITC-LA) from blood into the substantia nigra (SN) and striatum suggesting damage to the blood–brain barrier (BBB). The factors contributing to the BBB leakage could have included neuroinflammation, loss of DA neuron control of barrier function, or a combination of both. In order to determine which factor(s) was responsible, we assessed BBB integrity using the FITC-LA technique in wild-type (WT), tumor necrosis factor alpha (TNF-α) knockout (KO), and minocycline (an inhibitor of microglia activation) treated mice 72 h following treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with WT mice, TNF-α KO mice treated with MPTP showed reduced FITC-LA leakage, decreased numbers of activated microglia, and reduced proinflammatory cytokines (TNF-α and interleukin 1β) associated with significant MPTP-induced DA neuron loss. In contrast, minocycline treated animals did not exhibit significant MPTP-induced DA neuron loss although their FITC-LA leakage, numbers of activated microglia, and MPTP-induced cytokines were markedly attenuated. Since both TNF-α KO and minocycline treatment attenuated MPTP-induced BBB dysfunction, microglial activation, and cytokine increases, but had differential effects on DA neuron loss, it appears that neuroinflammation and not DA neuron loss was responsible for disrupting the blood–brain barrier integrity.

The blood brain barrier (BBB) is a highly dynamic interface between the central nervous system and periphery. The BBB is comprised of a number of components and is part of the larger neuro(glio)vascular unit. Current literature suggests that psychostimulant drugs of abuse alter the function of the BBB which likely contributes to the neurotoxicities associated with these drugs. In both preclinical and clinical studies, psychostimulants including methamphetamine, MDMA, cocaine, and nicotine, produce BBB dysfunction through alterations in tight junction protein expression and conformation, increased glial activation, increased enzyme activation related to BBB cytoskeleton remodeling, and induction of neuroinflammatory pathways. These detrimental changes lead to increased permeability of the BBB and subsequent vulnerability of the brain to peripheral toxins. In fact, abuse of these psychostimulants, notably methamphetamine and cocaine, has been shown to increase the invasion of peripheral bacteria and viruses into the brain. Much work in this field has focused on the co-morbidity of psychostimulant abuse and human immunodeficiency virus (HIV) infection. As psychostimulants alter BBB permeability, it is likely that this BBB dysfunction results in increased penetration of the HIV virus into the brain thus increasing the risk of and severity of neuroAIDS. This review will provide an overview of the specific changes in components within the BBB associated with psychostimulant abuse as well as the implications of these changes in exacerbating the neuropathology associated with psychostimulant drugs and HIV co-morbidity.

Despite decades of research and the development of a large group of animal models, our understanding of the mechanisms responsible for the progressive loss of dopamine neurons in Parkinson's disease (PD) is unknown. So-called neuroprotective studies demonstrate that a vast group of molecules readily attenuate the dopamine (DA) neuron loss produced by DA neurotoxin insult. Despite these successes, these neuroprotective strategies have been surprisingly ineffective in patients. This may reflect the fact that the initial pathogenic event and the subsequent disease progression is a consequence of different mechanisms. As we began to think about this disconnect, we discovered that animals exposed to DA neurotoxins exhibited blood–brain barrier (BBB) dysfunction. If the BBB in PD patients is disrupted, then the barrier that normally segregates peripheral vascular factors from brain parenchyma is no longer present. Immune cells could then enter brain and produce a self-perpetuating (progressive) degenerative process. In this review, we propose that peripheral immunity contributes to the degenerative process of PD and may be responsible for the progressive nature of the disease. This hypothesis is supported by a broad and diverse literature that is just beginning to come together to suggest that PD is, in part, an autoimmune disease. In order to understand this hypothesis, the reader must question the conventional wisdom that the BBB is intact in PD, the brain is an immune privileged area, and that pathogenic insult and disease progression may reflect different mechanisms.

The blood–brain barrier (BBB) is a tightly regulated barrier in the central nervous system. Though the BBB is thought to be intact during neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD), recent evidence argues otherwise. Dysfunction of the BBB may be involved in disease progression, eliciting of peripheral immune response, and, most importantly, altered drug efficacy. In this review, we will give a brief overview of the BBB, its components, and their functions. We will critically evaluate the current literature in AD and PD BBB pathology resulting from insult, neuroinflammation, and neurodegeneration. Specifically, we will discuss alterations in tight junction, transport and endothelial cell surface proteins, and vascular density changes, all of which result in altered permeability. Finally, we will discuss the implications of BBB dysfunction in current and future therapeutics. Developing a better appreciation of BBB dysfunction in AD and PD may not only provide novel strategies in treatment, but will prove an interesting milestone in understanding neurodegenerative disease etiology and progression.

Animal models have been an essential tool for researchers and clinicians in their efforts to study and treat Parkinson's disease (PD). Thus, the various ways 6-hydroxydopamine is employed, the use of MPTP in rodents and nonhuman primates, the prenatal exposure to bacterial endotoxin, the postnatal exposure to environmental toxins such as paraquat and rotenone, the assessment of dopamine (DA) neurons in genetic knockout mouse, and even the behavioral analysis of fruit flies and worms have added significantly to our knowledge base of PD—or have they? Are these animal models manifesting a true model of PD? Have the 7786 published studies (to date) on PD with animal models led to a clearer understanding of its etiology, treatment, or progression? In this review we critically assess this question. We begin with a succinct history of the major contributions, which have led to the current animal models of PD. We then evaluate the primary issue of the progressive loss of DA neurons, which, except for a few studies, has not been addressed in animal models of PD, even though this is the major pathological characteristic of the disease. Lastly, we discuss the possibility that more than one risk factor for PD may be necessary to develop an animal model that shows synergy—the progressive loss of DA neurons. Thus, the multiple hit hypothesis of PD—that is, the effect of more then one risk factor—may be the start of new era in animal models of PD that is one step closer to mimicking the pathology of PD in humans.

It is estimated that only 5-10% of dopamine (DA) neurons implanted into the striatum of patients undergoing fetal-nigral transplantation as a treatment for Parkinson's Disease survive. Because it is often necessary to store fetal tissue prior to transplantation, we evaluated various storage parameters that could influence DA neuron viability in rostral mesencephalic tegmentum (RMT) cultures using tyrosine hydroxylase immunoreactive (THir) cell counts as an index of DA neuron survival. A high K+ hibernation media (HM) was used in all studies. We found that RMT cell viability and THir cell counts decreased as storage duration increased (up to 120 h). Storage at 37°C in HM killed all cells, while storage at 10°C yielded higher survival rates than 4° C. In comparison to trypsinization, mechanical dissociation of tissue increased cell viability. Neutral pH and a storage density of at least 1 × 10 6 cells/mL were found to be optimal, while striatal coculture of RMT cells with striatal feeder layers increased THir viability up to 16-fold in comparison to monocultures. The nurturing effect of striatal coculture may be explained by the release of autotrophic factors, and we tested this hypothesis by supplementing the HM with human placental cord serum (HPCS, 8%), glial-derived neurotrophic factor (GDNF; 10 μg/mL), and brain-derived neurotrophic factor (BDNF; 10 μg/mL). GDNF and HPCS supplements increased RMT cell viability by 10-15%, while GDNF, BDNF, and HPCS increased viability of THir cells by approximately 40% at all time points studied. As Klenow enzyme labeling technique indicated that 33% of stored RMT cells were undergoing apoptosis, we found that GDNF, BDNF, and HPCS reduced apoptosis by 50%. DNA laddering and DAPI nuclear stain confirmed the presence of apoptosis in hibernated RMT cells, leading us to postulate that the high viability counts seen with trypan blue exclusion are misleading.

A technique for isolating mitotic progenitor cells from the embryonic rostral mesencephalon is described. Culture of the progenitor cells in complete media with subsequent staining for neuron specific enolase (NSE) revealed that only 0.6% of the cells were NSE immunoreactive. Coculturing the progenitor cells with established striatal cultures did not result in conversion of any of the cells to the dopamine neuron phenotype (tyrosine hydroxylase immunoreactive (THir) neurons). In contrast, co-culture of progenitor cells with established mesencephalic cultures produced a statistically significant, and in some cases (three of twelve), dramatic increase in the number of THir cells. The THir cells that were present had more pronounced process extension than those observed in mesencephalic mono-cultures. Culturing progenitor cells in transwell baskets that were continuously exposed to media but physically separated from established mesencephalic cultures growing underneath the baskets led to the conversion of only a few progenitor cells to THir neurons in four of twelve transwell studies suggesting that cell-cell contact between progenitor cells and mesencephalic cells is required for the conversion. This co-culture technique also increased the number of THir neurons in the mesencephalic cultures although the increase was not profound enough to explain the increase observed in traditional co-culture. These data suggest that mitotic progenitor cells can be isolated from fetal rat tissue and successfully converted to the dopamine neuron phenotype. Progenitor-mesencephalic co-culture appears to increase the number of THir cells in both tissue sources mediated in part by soluble factor(s) although cell-cell contact and presumably extracellular matrix proteins play a more substantial role. These progenitor cells may prove useful as a tissue source for transplantation procedures in Parkinson's disease.

Abstract This case considers underdosing of analgesics as a prime contributor to hypertension in diffuse axonal injury (DAI) patients who are being mechanically ventilated. In the air medical environment, obtunded patients' hemodynamic parameters are the primary tools available in diagnosing complex disorders such as an acute rise in intracranial pressure (ICP) when invasive ICP monitoring is not available. Therefore, differential diagnoses must follow a continuum, from most severe to least, in order to deal with sudden-onset hypertension rapidly. Not until all critical differentials have been eliminated is analgesia considered. Mimicking the signs of ICP, a compensatory rise in the mean arterial pressure (MAP) is displayed in an acute pain response for mechanically ventilated patients. Therefore, poor analgesic coverage should be considered early in DAI patients who are being ventilated, especially when an increased metabolic drive may be occurring, forcing the therapeutic dosing intervals to be increased. This patient was transferred from Europe back to North America via a fixed wing aircraft, a 16-hour transport time. [ABSTRACT FROM AUTHOR]

We describe the computational simulations and damage assessments that we provided in support of a tabletop exercise (TTX) at the request of NASA's Near-Earth Objects Program Office. The overall purpose of the exercise was to assess leadership reactions, information requirements, and emergency management responses to a hypothetical asteroid impact with Earth. The scripted exercise consisted of discovery, tracking, and characterization of a hypothetical asteroid; inclusive of mission planning, mitigation, response, impact to population, infrastructure and GDP, and explicit quantification of uncertainty. Participants at the meeting included representatives of NASA, Department of Defense, Department of State, Department of Homeland Security/Federal Emergency Management Agency (FEMA), and the White House. The exercise took place at FEMA headquarters. Sandia's role was to assist the Jet Propulsion Laboratory (JPL) in developing the impact scenario, to predict the physical effects of the impact, and to forecast the infrastructure and economic losses. We ran simulations using Sandia's CTH hydrocode to estimate physical effects on the ground, and to produce contour maps indicating damage assessments that could be used as input for the infrastructure and economic models. We used the FASTMap tool to provide estimates of infrastructure damage over the affected area, and the REAcct tool to estimate the potential economic severity expressed as changes to GDP (by nation, region, or sector) due to damage and short-term business interruptions. [ABSTRACT FROM AUTHOR]