Search

Objective: This 2-year observational study aimed to test the feasibility of implementing a pediatric stroke triage-setup that connected frontline providers with vascular neurologists and to examine final diagnoses in children triaged for suspected stroke.Methods: Prospective, consecutive registration of children with suspected stroke triaged by a team of vascular neurologists from Jan 1st, 2020 and through Dec 2021, Eastern Denmark (census 530,000 children). Based on the provided clinical information, the children were triaged to either assessment at the Comprehensive Stroke Center (CSC) in Copenhagen or to a pediatric department. All included children were retrospectively followed-up for clinical presentations and final diagnosis.Results: A total of 163 children with 166 suspected stroke events were triaged by the vascular neurologists. Cerebrovascular disease was present in 15 (9.0%) suspected stroke events; one child had intracerebral hemorrhage, one had subarachnoid hemorrhage, two children presented with three TIA events and nine children presented with 10 ischemic stroke events. Two children with ischemic stroke were eligible for acute revascularization treatment of which both were triaged to the CSC. The sensitivity of the triage by acute revascularization indication was 1.00 (95% confidence interval (95% CI): 0.15–1.00) and specificity 0.65 (95% CI: 0.57–0.73). Non-stroke neurological emergencies were present in 34 (20.5%) children, including seizures in 18 (10.8%) and acute demyelinating disorders in 7 (4.2%).Conclusion: Implementing regional triage-setup that connected frontline providers to vascular neurologists was feasible; this system was activated for the majority of children with ischemic stroke according to an expected incidence and led to identification of children eligible for revascularization treatments.

Supplemental Digital Content is Available in the Text.

A choroideremia carrier with blurred vision in her left eye was found to have a large unilateral vitelliform lesion in the fovea. Carrier retinopathy rarely involves the center of the fovea, but this case shows that it may happen.

ABSTRACTThis paper examines relations between radical left activists with citizenship and migrants in precarious conditions. It is based on ethnographic fieldwork conducted in 2013–2016 in the city of Malmö, an important site of pro-migrant and anti-racist activism in Sweden. Examples discussed in the paper concern the prevalence of highly educated women among the activists, the engagement of LGBTQ activists, and the fact that many activists themselves have migrant backgrounds. The alliances, friendships, and alternative structures they forge are analyzed with regard to two groups of precarious migrants in Malmö: the so-called undocumented migrants; and the Roma migrants from southeastern Europe. The paper shows how radical activism contributes to a solidarity-based ethnic diversity in the city that opposes the growing anti-immigrant stance in Sweden on the national level.

•Pediatric NMOSD and MOG antibody-associated disease are rare.•One-third of anti-MOG-positive children relapsed.•In pediatric ADEM, only anti-MOG-positive children relapsed.•The overall risk of relapse after pediatric ADEM was low.

For over 100 years, Underwriters Laboratories' ever-recognizable UL mark has been a beacon of safety and peace of mind, guiding consumers to reputable electrical products that have been rigorously tested [...]

Older patients often have multimorbidity, frequently resulting in polypharmacy. Independently, multimorbidity and polypharmacy are among the biggest risk factors for inappropriate medication, adverse drug reactions, adverse drug events and morbidity, leading to patient harm and hospitalisations. After a medication review, discontinuation of medication or deprescribing is one of the most common recommendations but is likely to be ignored. The deprescribing process includes some or all of the following elements: a review of current medications, identification of medications to be discontinued, a discontinuation regimen, involvement of patients and a review with follow-up. In addition to the complexity presented by prescribing or deprescribing for older multimorbid patients, other factors act as barriers to discontinuation of medications in these patients; these include interprofessional relationships, difficulties with medication reviews, deficiencies in knowledge and evidence and patients’ preferences/resistance to change. These challenges are compounded by the need to manage the shared treatment of multiple conditions by several prescribers from different specialties based on disease-specific guidelines without evidence of effects on the older, frailer, multimorbid patients. The interdisciplinary effort in the treatment of such patients needs to improve to ensure that we treat the patient holistically and not just the individual conditions of the multimorbid patient, according to guidelines. We must first, however, equip prescribers to identify instances where deprescribing is appropriate and then make the necessary changes to pharmacotherapy.

Mounting an antibody response capable of discriminating amongst and appropriately targeting different parasites is crucial in host defence. However, cross-reactive antibodies that recognize (bind to) multiple parasite species are well documented. We aimed to determine if a higher inoculating dose of one species, and thus exposure to larger amounts of antigen over a longer period of time, would fine-tune responses to that species and reduce cross-reactivity. Using the Plasmodium chabaudi chabaudi (Pcc)–Nippostrongylus brasiliensis (Nb) co-infection model in BALB/c mice, in which we previously documented cross-reactive antibodies, we manipulated the inoculating dose of Pcc across 4 orders of magnitude. We investigated antigen-specific and cross-reactive antibody responses against crude and defined recombinant antigens by enzyme linked immunosorbent assay, Western blot and antibody depletion assays. Contrary to our hypothesis that increasing exposure to Pcc would reduce cross-reactivity to Nb, we found evidence for increased avidity of a subpopulation of antibodies that recognized shared antigens. Western blot indicated proteins of apparent monomer molecular mass 28 and 98 kDa in both Nb and Pcc antigen preparations and also an Nb protein of similar size to recombinant Pcc antigen, merozoite surface protein-119. The implications of antibodies binding antigen from such phylogenetically distinct parasites are discussed. [ABSTRACT FROM AUTHOR]

In meiosis I, the centromeres of sister chromatids are pulled, together, toward the same pole of the spindle. In mitotis, the opposite is true—sister centromeres are pulled apart. This study explores the manner in which mitotic outer kinetochores are shed to allow assembly of meiotic kinetochore structures.

Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adultadolescent GCTs. One distinctive feature is the absence of a progenitor stage, such as carcinoma in situ or gonadoblastoma, which are seen in adultadolescent GCTs, except spermatocytic seminoma. The primordial germ cell (PGC) is the suggested origin of all GCTs, with variations in histology reflecting differentiation stage. Expression of pluripotency transcription factors OCT-34, NANOG, and AP-2 in germinomasseminomasdysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from abnormal extraembryonic differentiation. In pediatric GCTs, origin is suggested at an earlier developmental stage because of predisposing genetic factors, although responsible genes remain largely unknown. Some extragonadal GCTs have been linked to overexpression of the KITKITLG system, allowing for survival of aberrantly migrated ectopic PGCs. Infant gonadalsacrococcygeal GCTs may be caused by apoptosis-related pathways, consistent with an association with polymorphisms in BAK1. Although recent advances have identified candidate pathways, further effort is needed to answer central questions of pathogenesis of these fascinating tumors.

The prevalence of personal music (PM) system use with earphones is high among young adults. Although previous research has demonstrated that the majority of these adults may not be listening at levels or for durations considered dangerous, the long-term consequences of PM system use are not fully understood. In this report the relationship between self-reported PM use (i.e., non, light, moderate, or heavy) and peripheral auditory function as assayed through distortion product otoacoustic emission (DPOAE) components and fine structure was explored. The purpose was to evaluate the relationship between PM system use and peripheral auditory function.

The article focuses on the perspective of a law student from Washburn Law School in Topeka, Kansas, who visited the Shawnee County Correctional Facility for the first time. It says that the visit of the student along with his classmates aim to understand inner workings in the jail and its place in the wider criminal justice system. According to deputy director Brian Cole, suicide is their biggest concern and the highest risk done by an inmate as their first 72 hours of detention settles in.

Cdc14 is a member of the dual-specificity phosphatase family, which is essential for faithful cell cycle progression in eukaryotic cells of different origin. The function of human Cdc14A (hCdc14A), however, has not been fully elucidated as only few physiological substrates have been identified. To gain insight into the biological role of Cdc14A, we performed a yeast two-hybrid screen designed to isolate substrates of this human phosphatase. Using this genetic approach, we here report the identification of Erk3, an atypical mitogen-activated protein kinase (MAPK), as a specific binding partner of hCdc14A. GST pull-down assays show that Erk3 interacts directly with hCdc14A in vitro via its unique C-terminal domain. Furthermore, biochemical analysis reveals that hCdc14A can remove cyclin-dependent kinase (Cdk)-mediated phosphorylation of Erk3 in vitro raising the possibility that Erk3 may be a potential substrate for hCdc14A in vivo. Consistent with a physiologically relevant cross-talk in vivo, we find that Cdc14A forms a stable complex with Erk3 in human cells independent of its intrinsic phosphatase activity but mediated by its regulatory C-terminal domain. We show that hCdc14A impacts the emerging signaling pathway between Erk3 and MK5, a MAPK-activated protein kinase. We document that hCdc14A upregulation leads to redistribution of the Erk3 substrate MK5 from the nucleus to the cytoplasm. In addition, we find that hCdc14A stabilizes complex formation between Erk3 and its binding partner cyclin D3, a D-type cyclin implicated in both cellular proliferation and differentiation. Collectively, our findings suggest an intimate functional relationship between the Cdc14A phosphatase and the Erk3 kinase in signaling pathways that regulate key cell-fate decisions in human cells.

Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPNover-expressed in CIS compared to normal adult testis. PDPNencodes podoplanin (Aggrus, human gp36, T1A-2), a transmembrane glycoprotein expressed in lymphatic endothelium and various solid tumours. To examine a potential role for PDPNin testicular neoplasms and during testicular development, we investigated its expression pattern during the development of human testis and in a series of testicular CIS, gonadoblastoma and overt germ-cell tumours. We established by RT-PCR and by immunohistochemistry with a gp36 antibody that PDPNmRNA and the protein product were expressed in testes with germ-cell neoplasms but not in the normal adult testis. We also found gp36 expression in early foetal gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has a function in developing testis, most likely at the level of cell–cell interactions among pre-meiotic germ cells and immature Sertoli cells.Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPNover-expressed in CIS compared to normal adult testis. PDPNencodes podoplanin (Aggrus, human gp36, T1A-2), a transmembrane glycoprotein expressed in lymphatic endothelium and various solid tumours. To examine a potential role for PDPNin testicular neoplasms and during testicular development, we investigated its expression pattern during the development of human testis and in a series of testicular CIS, gonadoblastoma and overt germ-cell tumours. We established by RT-PCR and by immunohistochemistry with a gp36 antibody that PDPNmRNA and the protein product were expressed in testes with germ-cell neoplasms but not in the normal adult testis. We also found gp36 expression in early foetal gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has a function in developing testis, most likely at the level of cell–cell interactions among pre-meiotic germ cells and immature Sertoli cells.

We compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia.

The active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces caspase-independent apoptosis in MCF-7 and T47D breast cancer cells. Before the appearance of apoptotic cells at Day 4 after the addition of 1,25(OH)2D3, the MCF-7 cells are sensitized to the caspase-mediated apoptosis induced by TNF. We studied the mechanism underlying the cross talk between these 2 distinct death pathways in MCF-7 and T47D cells. Whereas 1,25(OH)2D3 pre-treatment enhanced TNF-induced apoptosis of TNF sensitive MCF-7 cells, it failed to render TNF resistant T47D cells sensitive to this cytokine. Opposing to an earlier report suggesting that cytosolic phospholipase A2 (cPLA2) mediates the 1,25(OH)2D3-induced sensitization to TNF, we could not detect any cPLA2 protein in MCF-7 cells and its overexpression had no effect on cellular sensitivity to 1,25(OH)2D3 or the combination with TNF. The sensitization of MCF-7 cells to TNF-induced apoptosis by pre-treatment with 1,25(OH)2D3 may instead be partially explained by an increased surface expression of the TNF receptor 1 (TNF-R1). In line with this, not only the TNF-induced activation of caspases and apoptosis but also that of NF-κB was enhanced by 1,25(OH)2D3 pre-treatment. Furthermore, 1,25(OH)2D3 enhanced TNF-induced NF-κB activation in T47D cells suggesting that it potentiates TNF signaling in general. Interestingly, the lysosomal protease cathepsin B, which expression is up-regulated by 1,25(OH)2D3, was released from the lysosomes upon TNF treatment, and inhibition of its activity rescued 1,25(OH)2D3 treated MCF-7 cells from TNF-induced apoptosis. In conclusion, 1,25(OH)2D3 may enhance TNF-induced apoptosis by increasing the expression of both the TNF-R1 and cathepsin B. © 2001 Wiley-Liss, Inc. © 2001 Wiley-Liss, Inc.

Using the Boyden chamber invasion assay, the effect of 1α,25-dihydroxyvitamin D3[1α,25(OH)2D3] on the invasiveness of the highly invasive, oestrogen receptor-negative human breast cancer cell line MDA-MB-231 was examined. The MDA-MB-231 cells were shown to contain high-affinity receptors for 1α,25(OH)2D3with a Kdof 1.5 × 10−11M. When the cells were treated with 1α,25(OH)2D3for 4 days before the assay was performed, a dose-dependent inhibition of their invasive potential was demonstrated. Fifty per cent inhibition of invasion was obtained with a concentration of 13 pM of 1α,25(OH)2D3. However, when the cells were treated for only 6 h during the assay, no inhibitory effect was seen. The process of migration was also affected by treatment with 1α,25(OH)2D3for 4 days, although the inhibition was not of the same magnitude as seen for the invasion. Fifty per cent inhibition of migration occurred at a concentration of 3.2 nM of 1α,25(OH)2D3(250 times higher than in the invasion assay). Inhibition of invasion and migration was not due to the known anti-proliferative effect of 1α,25(OH)2D3, as no growth reduction could be demonstrated with treatment up to 5 days. Based on the present investigation it can therefore be concluded that 1α,25(OH)2D3is able to inhibit tumour cell invasiveness by a mechanism which is not exclusively based on its anti-proliferative and anti-migrative effects.

11α,25‐dihydroxyvitamin3(VD) is a nuclear hormone that has important cell regulatory functions but also a strong calcemic effect. EB1089 is a potent antiproliferative VD analogue, which has a modified side chain resulting in increased metabolic stability and a selective functional profile. Since EB1089 is considered for potential systemic application, it will be investigated to what extent its recently identified metabolites (hydroxylated at positions C26 and C26a) contribute to biological profile of the VD analogue.2Limited protease digestion analysis demonstrated that EB1089 is able to stabilize the high affinity ligand binding conformation of the VDR, starting at concentrations of 0.1 nMand affecting up to 80% of all receptor molecules. The metabolites EB1445 and EB1470 showed to be 100 fold less potent than EB1089, whereas the remaining three metabolites (EB1435, EB1436 and EB1446) showed a clearly reduced ability to stabilize the high affinity ligand binding conformation. Interestingly, at pharmacological concentrations all EB1089 metabolites stabilized a second, apparently lower affinity conformation to a much higher extent than EB1089.3In reporter gene assays all metabolites showed lower potency than EB1089. Moreover, the preference of EB1089 for activation of VDR binding to sites formed by inverted palindromic arrangements spaced by nine nucleotide (IP9‐type VD response elements) appeared to be reduced (with EB1445 and EB1470) or completely lost (with EB1435, EB1436 and EB1446). The ranking of EB1089 and its metabolites that was obtained by limited protease digestion and reporter gene assays was confirmed by an analysis of their antiproliferative effect in breast cancer cells.4The potency and selectivity of the EB1089 metabolites in mediating gene regulatory effects was found to be drastically reduced in comparison to the parent compound suggesting that the contribution of the metabolites to the biological effect of EB1089 is minor. However, the compounds showed to be interesting tools for understanding the selective biological profile of EB1089.

An efficient external sorting algorithm with minimal space requirement is presented in this article. The average number of passes over the data is approximately 1 +Ln(N + 1)/4B, whereN is the number of records in the file to be sorted, andB is the buffer size. The external storage requirement is only the file itself, no additional disk space is required. The internal storage requirement is four buffers: two for input, and two for output. The buffer size can be adjusted to the available memory space. A stack of size log2N is also required.

Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, the impacts of such interactions on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce nematode infection and measured the effects on both nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary reservoir (Peromyscusspp.). Treatment significantly reduced nematode infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both nematodes and SNV were in better condition and survived up to four times longer than uninfected or singly infected mice. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.