A pilot evaluation of an advocacy programme on knowledge, empowerment, family-school partnership and parent well-being.

BACKGROUND: Internationally, it has been recognised that parents need to advocate for their children with disabilities to receive services. However, many parents find advocacy difficult because of systemic and logistical barriers. As such, parents of children with disabilities may seek a special education advocate to help them understand their child's rights and secure services. Yet little research has been conducted about programmes to develop special education advocates. METHODS: In this study, we conducted a comparison study to determine the association of an advocacy programme (i.e. the Volunteer Advocacy Project) on a primary outcome (i.e. special education knowledge) and other outcomes (i.e. family-school partnership, empowerment and parent well-being). Specifically, in 2017, 34 participants, all mothers of children with disabilities, were recruited from disability organisations in the USA. Seventeen mothers participated in the intervention group (i.e. the advocacy training), while 17 mothers participated in the wait list control group. The Volunteer Advocacy Project is a 36 hr advocacy training for individuals to gain instrumental and affective knowledge to advocate for their own children with disabilities and for other families. All participants completed a pre-survey and post-survey; only intervention group participants completed a 6-month follow-up survey. RESULTS: Compared with 17 wait list control group participants, the 17 intervention group participants demonstrated improvements in special education knowledge, P = 0.002, η2  = 0.32, and self-mastery, P = 0.04, η2  = 0.15, and decreases in the quality of family-school partnerships, P = 0.002, η2  = 0.32. At the follow-up survey, intervention group participants demonstrated increases in empowerment, P = 0.04, η2  = 0.29, and special education knowledge, P = 0.02, η2  = 0.38. CONCLUSIONS: Implications for research including the need for a randomised controlled trial are discussed; also, practitioners need to evaluate advocacy training programmes regarding their effectiveness.

NXCL-4950, a novel composite applicable to peripheral skin, is capable of increasing skin temperature by enhancing capillary circulation.

BACKGROUND: Rapid skin warming and prompt correct medical treatment lead to dramatic improvement in patients with peripheral capillary-related damage, such as injuries, Raynaud disease and frostbite. AIM: To characterize a novel composite, NXCL-4950, for use in a cosmetic lotion. METHODS: The effects of NXCL-4950 on enhancing skin blood flow, skin temperature warming, and expansion of peripheral blood vessels and scalp microvessels were investigated. RESULTS: Monitoring by laser Doppler perfusion imaging and thermal imaging showed that application of NXCL-4950 to the hands increased skin blood flow and temperature relative to the control (or placebo) group. For the 20 participants with a high Raynaud Condition Score, application of NXCL-4950 to the skin resulted in a mean increase of 215.53% in microvessel diameter and mean increase of 164.96% in the speed of blood flow. When NXCL-4950 was applied to the scalp, the microvessels around the hair roots were clearly visible after 20 min. CONCLUSION: NXCL-4950 is a potential candidate for enhancing peripheral skin temperature, and might be useful in the treatment of capillary-related disorders.

Human Plasmodium knowlesi infections in Klang Valley, Peninsula Malaysia: a case series.

We report seven cases of naturally acquired human Plasmodium knowlesi infections which were admitted to our centre from July 2007 till June 2008. Diagnosis was confirmed by nested PCR. Cases of P. knowlesi infections, dubbed the fifth type of human malaria, have been reported in East Malaysia (Sabah and Sarawak) as well as in the state of Pahang in Peninsula Malaysia. These seven patients appear to be the first few reported cases of P. knowlesi infection in the Klang valley, Peninsula Malaysia. We then discuss the characteristics of human P. knowlesi infections, which include its natural hosts, responsible vectors, clinical presentation, and the treatment of such infections.

Solitary fibrous tumour of the pleura presenting with refractory non-insulin mediated hypoglycaemia (the Doege-Potter syndrome).

We report a case of a 61 year-old man who presented with refractory non-insulin mediated hypoglycaemia. A chest radiograph showed a right lung opacity, which was confirmed as a large intra-thoracic mass by computed tomography (CT) of the thorax. CT-guided biopsy with histological examination revealed features of a solitary fibrous tumour of low malignant potential. We discuss the association of solitary fibrous tumour of the pleura (SFTP) with hypoglycaemia, and the management of such rare tumours.

Antiphospholipid syndrome with pulmonary artery embolism and multiple venous thromboses.

We report a case of a 21-year-old university student with underlying lupus nephritis who presented with recurrent symptoms of fever, haemoptysis, and pleuritic chest pain. CT pulmonary angiogram confirmed pulmonary embolism in the right subsegmental pulmonary arteries. One week later, she developed left renal vein and left common iliac vein thromboses, with new emboli in the left subsegmental pulmonary arteries. We hereforth discuss the diagnostic issues of a patient with systemic lupus erythematosus (SLE) on corticosteroids therapy, and also treatment of the antiphospholipid syndrome.

Cytokine-mediated induction of anti-apoptotic genes that are linked to nuclear factor kappa-B (NF-kappaB) signalling in human islets and in a mouse beta cell line.

AIMS/HYPOTHESIS: The destruction of pancreatic beta cells leading to type 1 diabetes in humans is thought to occur mainly through apoptosis and necrosis induced by activated macrophages and T cells, and in which secreted cytokines play a significant role. The transcription factor nuclear factor kappa-B (NF-kappaB) plays an important role in mediating the apoptotic action of cytokines in beta cells. We therefore sought to determine the changes in expression of genes modulated by NF-kappaB in human islets exposed to a combination of IL1beta, TNF-alpha and IFN-gamma. METHODS: Microarray and gene set enrichment analysis were performed to investigate the global response of gene expression and pathways modulated in cultured human islets exposed to cytokines. Validation of a panel of NF-kappaB-regulated genes was performed by quantitative RT-PCR. The mechanism of induction of BIRC3 by cytokines was examined by transient transfection of BIRC3 promoter constructs linked to a luciferase gene in MIN6 cells, a mouse beta cell line. RESULTS: Enrichment of several metabolic and signalling pathways was observed in cytokine-treated human islets. In addition to the upregulation of known pro-apoptotic genes, a number of anti-apoptotic genes including BIRC3, BCL2A1, TNFAIP3, CFLAR and TRAF1 were induced by cytokines through NF-kappaB. Significant synergy between the cytokines was observed in NF-kappaB-mediated induction of the promoter of BIRC3 in MIN6 cells. CONCLUSIONS/INTERPRETATION: These findings suggest that, via NF-kappaB activation, cytokines induce a concurrent anti-apoptotic pathway that may be critical for preserving islet integrity and viability during the progression of insulitis in type 1 diabetes.

Subclavian artery stent fracture.

We report a case of a 52 year-old dentist who had stent implantation for a left subclavian artery stenosis. However, this was later complicated by a stent fracture within one week of stent placement. A chest radiograph showed two pieces of the fractured stent, which was confirmed by computed tomographic angiogram (CTA) of the affected artery. We then discuss the occurrence of stent fractures, which are not uncommon but serious complications of endovascular therapy.

Police Officers' Knowledge and Attitudes Toward Brain Death and Organ Donation in Korea.

BACKGROUND: Administrative processing by the police may affect the process involved in organ donation in the event of an accidental brain injury. The purpose of this study was to evaluate the knowledge and attitude of police toward brain-dead donors and organ donation. METHODS: This was a descriptive research study using a 41-item questionnaire. As of July 19, 2017, 11 police stations in Seoul had collected questionnaires completed by 115 police officers. Data were analyzed using SAS (version 9.4) software. RESULTS: There were statistically significant differences in the scores on knowledge about brain death/donation according to religion (P = .022). Attitude was significantly positively correlated with the knowledge about brain-death organ donation (P = .029). CONCLUSION: It is necessary to understand and cooperate with the police when processing brain death organs from accidents. Education about organ donation can enhance the information and knowledge of the police and can also help to establish a positive attitude about organ donation.

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding.

This corrects the article DOI: 10.1038/onc.2011.331.

Cylindroid lamella-particle complexes in lymphoma cells by northern pike (Esox lucius).

Cells of the malignant lymphoma of northern pike of Canada contained cylindrical structures with central cores of cytoplasmic elements and walls composed of lamellae in a spiral arrangement, separated by ribosome-like particles or by membranes. These cylindroids were similar, if not identical, to structures in the cells of certain human lymphomas and leukemias. In cross and longitudinal sections, the lamellae showed a pattern of light and dark bands resulting in an approximately 95 A-period that has not been described in the human cylindroids.

Functional Image-guided Radiotherapy Planning for Normal Lung Avoidance.

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.

Orexin (hypocretin) neurons contain dynorphin.

Orexins (also called hypocretins) are peptide neurotransmitters expressed in neurons of the lateral hypothalamic area (LHA). Mice lacking the orexin peptides develop narcolepsy-like symptoms, whereas mice with a selective loss of the orexin neurons develop hypophagia and severe obesity in addition to the narcolepsy phenotype. These different phenotypes suggest that orexin neurons may contain neurotransmitters besides orexin that regulate feeding and energy balance. Dynorphin neurons are common in the LHA, and dynorphin has been shown to influence feeding; hence, we studied whether dynorphin and orexin are colocalized. In rats, double-label in situ hybridization revealed that nearly all (94%) neurons expressing prepro-orexin mRNA also expressed prodynorphin mRNA. The converse was also true: 96% of neurons in the LHA containing prodynorphin mRNA also expressed prepro-orexin mRNA. Double-label immunohistochemistry confirmed that orexin-A and dynorphin-A peptides were highly colocalized in the LHA. Wild-type mice and orexin knock-out mice showed abundant prodynorphin mRNA-expressing neurons in the LHA, but orexin/ataxin-3 mice with a selective loss of the orexin neurons completely lacked prodynorphin mRNA in this area, further confirming that within the LHA, dynorphin expression is restricted to the orexin neurons. These findings suggest that dynorphin-A may play an important role in the function of the orexin neurons.

The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance.

BACKGROUND: The development of antimicrobial guidelines is one way in which institutions attempt to control emerging resistance, but the real challenge falls on promoting and ensuring adherence to these guidelines. Investigating reasons for the prescribing of alternative antimicrobial agents outside of these guidelines is crucial for modifying practices that may adversely impact institutional antimicrobial goals. METHODS: Retrospective cross-referencing of computerized pharmacy printouts and concurrent manual medical record review. RESULTS: Approximately 25% (470/1893) of the patients requiring antimicrobial therapy reported an allergy to at least 1 antimicrobial agent. The most commonly reported antimicrobial allergy was penicillin (295/1893 [15.6%]). Eighty-five patients (18.1%) reported having an allergy to 2 or more antimicrobial agents. Only 4% (27/601) of the reported antimicrobial allergies contained documentation as to the nature of the specific allergic reactions, while a manual medical record review revealed that 32% (23/73) of the antimicrobial allergies contained documentation of the specific allergic reaction. Ninety-eight (39. 7%) of 247 patients reporting an allergy only to penicillin and/or cephalosporin received vancomycin in comparison with 247 (17.4%) of 1423 patients without any antimicrobial allergies (P<.001). Similarly, 53 (21.5%) of 247 patients with reported penicillin and/or cephalosporin allergies received levofloxacin compared with 114 (8.0%) of 1423 patients without any antimicrobial allergy (P<. 001). CONCLUSION: The incidence of penicillin allergy at our institution exceeds population averages. This finding, in combination with limited documentation of drug allergies, appears to lead to the prescribing of alternative antimicrobial agents that do not fit into institutional antimicrobial guidelines and, in some instances, may put the patient at risk for infection and/or colonization with resistant organisms. Use of these alternative agents may adversely impact the ability to manage emerging antimicrobial resistance.

Interferon-gamma-induced factor binding to the interleukin-4-responsive element of CD23b promoter in human tonsillar mononuclear cells: role in transient up-regulation of the interleukin-4-induced CD23b mRNA.

Stimulation of human tonsillar mononuclear cells with interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) rapidly induced the activation of distinct nuclear factors with different mobilities, both of which bind the IL-4 response element (IL-4RE) of CD23b promoter as examined by electrophoretic mobility shift assays (EMSA). Co-treatment of IL-4 and IFN-gamma induced, in addition to the two distinct complexes, a new complex with an intermediate mobility. The IL-4-induced complex reacted with anti-STAT (signal transducers and activators of transcription) 6, resulting in a supershift whereas the formation of the IFN-gamma-induced complex was inhibited by anti-STAT 1. The intermediate complex appeared to react with both anti-STAT 6 and anti-STAT 1. Although IFN-gamma alone did not induce CD23 mRNA transcription, Northern blot analysis revealed a transient up-regulation of the IL-4-induced CD23 mRNA by IFN-gamma within 2 h of IFN-gamma treatment in these tonsillar cells. The results suggest that the IL-4RE of the IL-4-inducible gene can accommodate both IL-4- and IFN-gamma-activated factors, such as STAT 6 and STAT 1, either in homodimeric or heterodimeric forms and the binding of these different proteins to the respective promoter may play a potential regulatory role in the IL-4-inducible gene expression.

Mechanism of interferon-gamma down-regulation of the interleukin 4-induced CD23/Fc epsilon RII expression in human B cells: post-transcriptional modulation by interferon-gamma.

It has been reported that the interleukin 4 (IL-4) specific induction of cell surface CD23 (Fc epsilon RII) is down-regulated by interferon-gamma (IFN-gamma) in monocytes and B cells. However, the molecular level at which the inhibition occurs seems to vary depending on the cell types. In normal human B cells, IFN-gamma inhibits the IL-4 induced de novo synthesis of CD23 at the level of gene expression. Analysis of inhibition kinetics suggested a rapid signal transmission by IFN-gamma. Yet the inhibitory action of IFN-gamma on CD23 mRNA accumulation appeared as a secondary response requiring a new protein synthesis. Through nuclear run-on transcription and mRNA stability studies, we further demonstrate that the IL-4 induced CD23 gene expression is down-regulated by IFN-gamma mainly at post-transcriptional levels by decreasing mRNA stability.

Reconstructions of populations of luteinizing hormone releasing hormone neurons in young and middle-aged rats reveal progressive increases in subgroups expressing Fos protein on proestrus and age-related deficits.

Fos expression has been used as a marker of activation of neuroendocrine cells including LHRH neurons. In this study, Fos protein was localized within LHRH neurons in young and middle-aged rats to trace the temporal and spatial pattern of LHRH neuronal activation associated with the preovulatory LH surge. Animals were killed during the late morning, afternoon, and evening of proestrus. Dual immunocytochemical protocols localized LHRH and LHRH/Fos neurons, and computer-assisted methods were used to reconstruct forebrain populations of single- and double-labeled LHRH neurons. Although a significant increase in the number of LHRH/Fos neurons was noted by evening in both age groups, a greater increase was observed in young (12% in morning, 28% in afternoon, and 62% by evening) compared with aging females (5% in morning, 10% in afternoon, and 40% by evening). Reconstructions of LHRH and LHRH/Fos neurons revealed time- and age-dependent differences in Fos expression within LHRH neurons. In young females, LHRH/Fos neurons were restricted to central regions of the population of LHRH neurons on the morning of proestrus. By evening, Fos expression was also observed in more peripheral and caudal LHRH neurons. In middle-aged females, Fos expression was restricted to ventral subgroups of LHRH neurons on the afternoon of proestrus. By evening, more LHRH neurons contained Fos protein, however, few were located in the dorsal aspect of the population. These data trace the progressive increase in activation of LHRH neurons during the preovulatory LH surge in young females and reveal deficits in this pattern of activation by middle age.

Global phylogeography of a cryptic copepod species complex and reproductive isolation between genetically proximate "populations".

The copepod Eurytemora affinis has a broad geographic range within the Northern Hemisphere, inhabiting coastal regions of North America, Asia, and Europe. A phylogenetic approach was used to determine levels of genetic differentiation among populations of this species, and interpopulation crosses were performed to determine reproductive compatibility. DNA sequences from two mitochondrial genes, large subunit (16S) rRNA (450 bp) and cytochrome oxidase I (COI, 652 bp), were obtained from 38 populations spanning most of the species range and from two congeneric species, E. americana and E. herdmani. Phylogenetic analysis revealed a polytomy of highly divergent clades with maximum sequence divergences of 10% in 16S rRNA and 19% in COI. A power test (difference of a proportion) revealed that amount of sequence data collected was sufficient for resolving speciation events occurring at intervals greater than 300,000 years, but insufficient for determining whether speciation events were approximately simultaneous. Geographic and genetic distances were not correlated (Mantel's test; r = 0.023, P = 0.25), suggesting that populations had not differentiated through gradual isolation by distance. At finer spatial scales, there was almost no sharing of mtDNA haplotypes among proximate populations, indicating little genetic exchange even between nearby sites. Interpopulation crosses demonstrated reproductive incompatibility among genetically distinct populations, including those that were sympatric. Most notably, two geographically distant (4000 km) but genetically proximate (0.96% 16S, 0.15% COI) populations exhibited asymmetric reproductive isolation at the F2 generation. Large genetic divergences and reproductive isolation indicate that the morphologically conservative E. affinis constitutes a sibling species complex. Reproductive isolation between genetically proximate populations underscores the importance of using multiple measures to examine patterns of speciation.

Chemical characterization of leptin-activated neurons in the rat brain.

Leptin has profound effects on food intake, body weight, and neuroendocrine status. The lack of leptin results in hormonal and metabolic alterations and a dramatic increase in body weight. Leptin acts in the brain, especially in the hypothalamus; however, the central nervous system sites that respond to leptin have not been examined comprehensively. In this study, we explored systematically the distribution of leptin-activated neurons throughout the rat brain. Furthermore, we investigated the chemical identity of subsets of these leptin-activated cells. Fos-like immunoreactivity (Fos-IR) was investigated in the rat brain after two different doses of leptin (1.0 mg/kg and 5.0 mg/kg) at 2 hours and 6 hours after injections. The induction of Fos-IR was observed in hypothalamic nuclei, including the paraventricular nucleus (PVH), the retrochiasmatic area (RCA), the ventromedial nucleus (VMH), the dorsomedial nucleus (DMH), the arcuate nucleus (Arc), and the ventral premammillary nucleus (PMV). In addition, leptin-induced Fos-IR was found in several nuclei of the brainstem, including the superior lateral and external lateral subdivisions of the parabrachial nucleus (slPB and elPB, respectively), the supragenual nucleus, and the nucleus of the solitary tract (NTS). By using double-labeling immunohistochemistry or immunohistochemistry coupled with in situ hybridization, leptin-activated neurons were found that contained cocaine- and amphetamine-regulated transcript mRNA in several hypothalamic nuclei, including the RCA, Arc, DMH, and PMV. In the Arc and DMH, leptin-induced Fos-IR was observed in neurons that expressed neurotensin mRNA. Dynorphin neurons in the VMH and in the Arc also expressed Fos-IR. In the brainstem, we found that cholecystokinin neurons in the slPB and glucagon-like peptide-1 neurons in the NTS were activated by leptin. We also investigated the coexpression of Fos-IR and the long form of the leptin receptor (OBRb) mRNA. We found double-labeled neurons surrounding the median eminence and in the RCA, Arc, VMH, DMH, and PMV. However, in brainstem sites, very little OBRb mRNA was found; thus, there were very few double-labeled cells. These results suggest that leptin stimulates brain pathways containing neuropeptides that are involved in the regulation of energy balance, autonomic homeostasis, and neuroendocrine status.

Characterization of CART neurons in the rat and human hypothalamus.

Cocaine- and amphetamine-regulated transcript (CART) is a recently described neuropeptide widely expressed in the rat brain. CART mRNA and peptides are found in hypothalamic sites such as the paraventricular nucleus (PVH), the supraoptic nucleus (SON), the lateral hypothalamic area (LHA), the dorsomedial nucleus of the hypothalamus (DMH), the arcuate nucleus (Arc), the periventricular nucleus (Pe), and the ventral premammillary nucleus (PMV). Intracerebroventricular administration of recombinant CART peptide decreases food intake and CART mRNA levels in the Arc are regulated by leptin. Leptin administration induces Fos expression in hypothalamic CART neurons in the PVH, the DMH, the Arc, and the PMV. In the current study, we used double label in situ hybridization histochemistry to investigate the potential direct action of leptin on hypothalamic CART neurons and to define the chemical identity of the hypothalamic CART neurons in the rat brain. We found that CART neurons in the Arc, DMH, and PMV express long form leptin-receptor mRNA, and the suppressor of cytokine signaling-3 (SOCS-3) mRNA after an acute dose of intravenous leptin. We also found that CART neurons in the parvicellular PVH, in the DMH and in the posterior Pe coexpress thyrotropin-releasing hormone (TRH) mRNA. CART neurons in the magnocellular PVH and in the SON coexpress dynorphin (DYN), and CART cell bodies in the LHA and in the posterior Pe coexpress melanin-concentrating hormone (MCH) and glutamic acid decarboxylase (GAD-67) mRNA. In the Arc, a few CART neurons coexpress neurotensin (NT) mRNA. In addition, we examined the distribution of CART immunoreactivity in the human hypothalamus. We found CART cell bodies in the PVH, in the SON, in the LHA, in the Arc (infundibular nucleus) and in the DMH. We also observed CART fibers throughout the hypothalamus, in the bed nucleus of the stria terminalis, and in the amygdala. Our results indicate that leptin directly acts on CART neurons in distinct nuclei of the rat hypothalamus. Furthermore, hypothalamic CART neurons coexpress neuropeptides involved in energy homeostasis, including MCH, TRH, DYN, and NT. The distribution of CART cell bodies and fibers in the human hypothalamus indicates that CART may also play a role in the regulation of energy homeostasis in humans.

Differential expression of orexin receptors 1 and 2 in the rat brain.

Orexins (hypocretins) are neuropeptides synthesized in the central nervous system exclusively by neurons of the lateral hypothalamus. Orexin-containing neurons have widespread projections and have been implicated in complex physiological functions including feeding behavior, sleep states, neuroendocrine function, and autonomic control. Two orexin receptors (OX(1)R and OX(2)R) have been identified, with distinct expression patterns throughout the brain, but a systematic examination of orexin receptor expression in the brain has not appeared. We used in situ hybridization histochemistry to examine the patterns of expression of mRNA for both orexin receptors throughout the brain. OX(1)R mRNA was observed in many brain regions including the prefrontal and infralimbic cortex, hippocampus, paraventricular thalamic nucleus, ventromedial hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. OX(2)R mRNA was prominent in a complementary distribution including the cerebral cortex, septal nuclei, hippocampus, medial thalamic groups, raphe nuclei, and many hypothalamic nuclei including the tuberomammillary nucleus, dorsomedial nucleus, paraventricular nucleus, and ventral premammillary nucleus. The differential distribution of orexin receptors is consistent with the proposed multifaceted roles of orexin in regulating homeostasis and may explain the unique role of the OX(2)R receptor in regulating sleep state stability.