Search

Objectives Stress experienced by mothers during the prenatal period can have negative impacts on offspring development. Elevated BMI in childhood in response to early stress experience is a particularly critical outcome of interest since high BMI in childhood is associated with diabetes, heart disease and stroke in later life. The primary objective of this study was to analyze pathways between prenatal stress and early childhood BMI at 54-months of age and to begin to explore ethnic variations in these pathways. Methods This study used the Growing Up in New Zealand (GUiNZ) dataset, which is a longitudinal, representative birth cohort study that began with recruiting pregnant women in 2009 and 2010 in Auckland, New Zealand. Path analysis modeling was used to explore risk and protective pathways between prenatal maternal stress and early childhood body mass index (BMI) at 54-months of age and differences by ethnicity (n = 5510). Results Prenatal stress was positively associated with early childhood BMI at 54-months and maternal nutrition behaviors and length of exclusive breastfeeding mediated this direct relationship ([chi].sup.2 (1) = 0.83, p = 0.36; AIC = 50,496). Mediation and moderation paths varied by ethnicity. Conclusions for Practice These findings contribute to the understanding of the intergenerational transmission of stress with respect to early childhood obesity. Reducing early stress exposure and/or addressing mediating and moderating factors linking stress experience with obesity development may prove to be more effective than attempting to alter health behaviors and trajectories in adulthood., Author(s): Charlotte V. Farewell [sup.1] , Jini Puma [sup.1] , Zaneta M. Thayer [sup.2] , Susan Morton [sup.3] Author Affiliations: (1) grid.430503.1, 0000 0001 0703 675X, Department of Community and [...]

The amyloid hypothesis posits that the amyloid-beta (A[beta]) protein precedes and requires microtubule-associated protein tau in a sort of trigger-bullet mechanism leading to Alzheimer's disease (AD) pathology. This sequence of events has become dogmatic in the AD field and is used to explain clinical trial failures due to a late start of the intervention when A[beta] already activated tau. Here, using a multidisciplinary approach combining molecular biological, biochemical, histopathological, electrophysiological, and behavioral methods, we demonstrated that tau suppression did not protect against A[beta]-induced damage of long-term synaptic plasticity and memory, or from amyloid deposition. Tau suppression could even unravel a defect in basal synaptic transmission in a mouse model of amyloid deposition. Similarly, tau suppression did not protect against exogenous oligomeric tau-induced impairment of long-term synaptic plasticity and memory. The protective effect of tau suppression was, in turn, confined to short-term plasticity and memory. Taken together, our data suggest that therapies downstream of A[beta] and tau together are more suitable to combat AD than therapies against one or the other alone., Introduction The amyloid cascade hypothesis dominates in the Alzheimer's disease (AD) field. It posits that amyloid-[beta] (A[beta]) and tau proteins are placed in a series with A[beta] upstream of tau, [...]

I could tell you that I'm brave, but brave is a lie. I could tell you that I'm doing well, but that denies the very nature of loss. This is [...]

Excessive alcohol consumption is associated with spontaneous burning pain, hyperalgesia, and allodynia. Although acetaldehyde has been implicated in the painful alcoholic neuropathy, the mechanism by which the ethanol metabolite causes pain symptoms is unknown. Acute ethanol ingestion caused delayed mechanical allodynia in mice. Inhibition of alcohol dehydrogenase (ADH) or deletion of transient receptor potential ankyrin 1 (TRPA1), a sensor for oxidative and carbonyl stress, prevented allodynia. Acetaldehyde generated by ADH in both liver and Schwann cells surrounding nociceptors was required for TRPA1-induced mechanical allodynia. Plp1-Cre [Trpa.sup.fl/fl] mice with a tamoxifen-inducible specific deletion of TRPA1 in Schwann cells revealed that channel activation by acetaldehyde in these cells initiates a NADPH oxidase-1-dependent (NOX1-dependent) production of hydrogen peroxide ([H.sub.2][O.sub.2]) and 4-hydroxynonenal (4-HNE), which sustains allodynia by paracrine targeting of nociceptor TRPA1. Chronic ethanol ingestion caused prolonged mechanical allodynia and loss of intraepidermal small nerve fibers in WT mice. While [Trpa1.sup.-/-] or Plp1-Cre [Trpa1.sup.fl/fl] mice did not develop mechanical allodynia, they did not show any protection from the small-fiber neuropathy. Human Schwann cells express ADH/TRPA1/NOX1 and recapitulate the proalgesic functions of mouse Schwann cells. TRPA1 antagonists might attenuate some symptoms of alcohol-related pain., Introduction Alcohol abuse and dependence are among the major health care problems in the world (1). The impact of alcohol abuse continues to grow as a result of the rising [...]

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that is characterized by extreme variability in symptoms, with females being less severely affected than males and presenting a higher proportion of asymptomatic carriers. The sex-related factors involved in the disease are not known. Here, we have utilized myoblasts isolated from FSHD patients (FSHD myoblasts) to investigate the effect of estrogens on muscle properties. Our results demonstrated that estrogens counteract the differentiation impairment of FSHD myoblasts without affecting cell proliferation or survival. Estrogen effects are mediated by estrogen receptor [beta] (ER[beta]), which reduces chromatin occupancy and transcriptional activity of double homeobox 4 (DUX4), a protein whose aberrant expression has been implicated in FSHD pathogenesis. During myoblast differentiation, we observed that the levels and activity of DUX4 increased progressively and were associated with its enhanced recruitment in the nucleus. ER[beta] interfered with this recruitment by relocalizing DUX4 in the cytoplasm. This work identifies estrogens as a potential disease modifier that underlie sex-related differences in FSHD by protecting against myoblast differentiation impairments in this disease., Introduction Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder with a prevalence of 1:20,000 to 1:15,000 worldwide (1). The major form of FSHD (FSHD1A, OMIM #158900) is associated [...]

Author(s): Carole Dalin (corresponding author) [1]; Yoshihide Wada [2, 3, 4, 5]; Thomas Kastner [6, 7]; Michael J. Puma [3, 4, 8] Recent hydrological modelling [1] and Earth observations [2, [...]

Author(s): Carole Dalin; Yoshihide Wada; Thomas Kastner; Michael J. Puma Nature 543, 700704 (2017); doi:10.1038/nature21403 In the Supplementary Information of this Letter, the first file, labelled Supplementary Table 1, linked [...]

This paper examines an alleged tomb group acquired in 1903 by the Metropolitan Museum of Art in New York. Many of the 43 objects are of high quality and made of valuable materials. Several of the most elegant are probably imports from Greek cities in southern Italy. Two of the silver objects, a strigil and an amphoriskos, are delicately punched with monograms that likely identify the owner and occupant of the tomb as Ramtha Murinas. This article makes a case for this identification, which in turn leads to the specific necropolis at Bolsena (Poggio Sala), where this tomb may have been discovered in the 19th century. An important feature of the tomb group appears in the use of special inscriptions designating 10 objects as suthina, or 'for the tomb.' This unusual practice is examined in the second haft of the paper.

The sensory neuron-specific G protein coupled receptors (SNSRs) have been described as a family of receptors whose expression in small diameter sensory neurons in the trigeminal and dorsal root ganglia suggests an implication in nociception. To date, the physiological function(s) of SNSRs remain unknown. Hence, the aim of the present study was to determine the effects of rat SNSR1 activation on nociception in rats. The pharmacological characterization of rat SNSR1 was initially performed in vitro to identify a specific ligand, which could be used subsequently in the rat for physiological testing. Among all ligands tested, [gamma]2-MSH was the most potent at activating rat SNSR1. Structure-activity relationship studies revealed that the active moiety recognized by rat SNSR1 was the C-terminal part of [gamma]2-MSH. The radiolabeled C-terminal part of [gamma]2-MSH, [gamma]2-MSH-6-12, bound with high affinity to membranes derived from rat skin and spinal cord, demonstrating the presence of receptor protein at both the proximal and distal terminals of dorsal root ganglia. To investigate the physiological role of SNSR, specific ligands to rat SNSR1 were tested in behavioral assays of pain sensitivity in rats. Selective rat SNSR1 agonists produced spontaneous pain behavior, enhanced heat and mechanical sensitivity when injected intradermally, and heat hypersensitivity when injected centrally, consistent with the localization of rat SNSR1 protein at central and peripheral sites. Together, these results clearly indicate that the SNSR1 plays a role in nociception and may provide novel therapeutic opportunities for analgesia.

Byline: Vincenzo Raieli (1), Giovanni Luca Eliseo (1), Michela La Vecchia (1), Girolama La Franca (1), Eleonora Pandolfi (1), Domenico Puma (1), Donatella Ragusa (1), Mario Eliseo (1) Keywords: Key words Stabbing headache; Juvenile population; Short paroxysms Abstract: Idiopathic stabbing headache is a not well known type of pain, and few reports have described the disorder in juvenile age. We report a sample of 30 juvenile patients with clinical features of stabbing headache after having excluded other pain disorders. We observed the presence of psychological features and the lack of association with migraine, unlike in the adult form. Some patients needed pharmacological treatment but the prognosis was good. Further studies are needed to better understand the mechanisms of pain and possible triggering factors. Author Affiliation: (1) Division of Child Neuropsychiatry, G. Ingrassia Hospital, AUSL 6, Via Gaetano La Loggia 3, I-90129 Palermo, Italy, e-mail: vinzi.raielk@inwind.it, Tel.: +39-091-7033275, Fax: +39-091-7033253, IT Article note: Received: 6 November 2001 / Accepted in revised form: 14 January 2002

The 'Prospects' study is the largest longitudinal study on academic achievement that has been undertaken in the US. It was legislated by Congress in 1989 to assess the progress of Chapter 1 programs on student achievement. However, it was not intended to answer specific questions about school desegregation plans in the city of St. Louis, MO. Especially on whether African American students perform better in segregated or in integrated schools. Nevertheless, 'Prospects' gives significant insights into this issue.

Research indicates that the Food Stamp Employment and Training Program has only a slight impact on average food stamp benefits, and no impact on a participant's earnings and/or employment. Discussion of the reasons behind these findings and the research methodologies used is also included.

* Parents of children and adolescents occasionally request nondisclosure of a diagnosis to the patient. This ethical dilemma was analyzed using a case in which parents of a child with cystic fibrosis demanded that the physician not reveal the diagnosis to their daughter. The case study helps to identify the specific clinical factors that may be considered when confronting similar dilemmas in other cases. Any justification for lying to the patient or hiding information must derive from clinical circumstances that override the basic moral duty to tell the truth. The physician, the disease, the patient, and the family are all pertinent to the ethical decision of disclosure. These factors may change over time with the natural history of the disease and the maturation of the patient. (AJDC. 1993;147:764-768), Pediatricians may face an ethical dilemma if parents do not want their sick child to know a diagnosis. Family dynamics, age of the child, nature of the illness and physicians' own values are all elements to be considered when parents request withholding a diagnosis. In one case, a native-Italian couple did not want their nine-year-old daughter told that she had cystic fibrosis. The physician initially went along with their decision, but became increasingly uncomfortable during the following nine years as the patient suffered three major complications. The parents continued to resist disclosure to their daughter. When the patient was 18 years old, the physician told her of her disease and the prognosis, still against the parents' wishes. This patient seemed to accept her parents' authority and the previous secrecy without question, probably due to cultural factors.

There are many anecdotes regarding the potential problems associated with physicians treating their own family members. However, there is little data to indicate how frequently this occurs. Furthermore, there have been no studies that focus on the attitudes of physicians towards treating family members or on the types of medical treatment that are administered to family members. A study was conducted to survey the opinions and experiences of physicians concerning the treatment of their family members. Questionnaires were sent to 691 members of the staff at a community hospital; 465 responses were received. As might be expected, most (99 percent) of the physicians reported that they had been asked for advice by family members. Eighty-three percent had prescribed medication for family members, and 80 percent had diagnosed illnesses. Fifteen percent had acted as the primary attending physician during a family member's hospital stay, and 9 percent had performed surgery on a family member. In some cases, the physicians refused requests of family members that they felt were inappropriate, were outside their field of expertise, or for which they felt their relationship was too close to permit objective judgement. However, 22 percent of the physicians reported having gone along with some requests, despite feeling uncomfortable about them. A third of the responding physicians reported observing a fellow physician giving inappropriate care to a family member. This study did not compare the quality of the medical care given to family members with the quality of medical care in general. However, the results indicate that many physicians are actively involved in the health care of close relatives. The potential problems associated with this kind of care are clear; further research and discussion should continue in this area. (Consumer Summary produced by Reliance Medical Information, Inc.)

Robert J. Moss is co-director, Section of Geriatric Medicine, and Clinical Ethics Scholar-in-Residence, Lutheran General Hospital. John La Pluma is director, Center for Clinical Ethics, Lutheran General Hospital, Park Ridge, [...]

Since 1981 the Food and Nutrition Service, U.S. Department of Agriculture has imposed financial penalties on 49 states with excessive overpayment errors in the Food Stamp program, many in more than one year, for a total of $423.5 million. Almost all have appealed the sanctions, and several have taken their appeal to the courts, questioning the fairness of the financial penalties. Although the quality control (QC) system holds all states to the same standard, payment error rates (defined as the proportion of total benefits paid erroneously) may reflect not only the administrative performance of an agency, but also the difficulty of the case load served and the characteristics of the social environment in which the program operates. To investigate the feasibility of adjusting states' overpayment error rates for differences on such external factors, we developed regression models for five components of the overpayment error rate. When fitted to the case-level data from the fiscal year (FY) 1984 QC sample, these models generally accounted for little of the variation in payment error. In addition, the resulting adjustments were sensitive to specific choices of explanatory variables and to year-to-year differences in the data. Thus it does not appear feasible to adjust states' overpayment error rates on the basis of available external factors. For purposes of exploration we separated the contributions to overpayment error rates into five parts (treating an underpayment as 0): the probability of an overpayment error occurring; the amount of an overpayment error should one occur; the probability of an ineligibility error occurring; the amount of an ineligibility error should one occur; and the size of the participant's food stamp allotment. This was done because most food stamp cases involve no errors, and thus the data have a large concentration of overpayment values at 0. For each component, a regression model related the outcome measure (occurrence of an error, the logarithm of the error amount, or the allotment amount) to case and area socioeconomic characteristics. The explanatory variables used represented six types of external factors: household size, earned income, unearned income, household resources, allowable income deductions, and population density. For the data from FY 1984, only the model for the allotment amount had a high value of [R.sup.2] (.87). When the separate results were combined to yield an adjusted payment error rate for each state, the changes from the state-reported error rate ranged from a reduction of 2.9 percentage points to an increase of 2.5 percentage points, and in 15 states the size of the change is statistically different from 0. Examinalion of alternative sets of explanatory variables in the five models, however, revealed substantial differences in magnitude and direction of the adjustments for a number of states. Fitting the five models to the data from FY 1985 gave further evidence of instability. Thus these statistical procedures for using available data to adjust payment error rates are not sufficiently stable to use in calculating financial penalties. KEY WORDS: Quality control; Regression adjustment; Welfare programs., 1. INTRODUCTION The Food and Nutrition Service (FNS) of the U.S. Department of Agriculture has used the food stamp overpayment error rate as the basis for financial liabilities and incentives [...]