Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects motor neurons, leading to progressive muscle weakness and loss of voluntary muscle control. While the exact ...cause of ALS is not fully understood, emerging research suggests that dysfunction of the nuclear envelope (NE) may contribute to disease pathogenesis and progression. The NE plays a role in ALS through several mechanisms, including nuclear pore defects, nucleocytoplasmic transport impairment, accumulation of mislocalized proteins, and nuclear morphology abnormalities. The LINC complex is the second biggest multi-protein complex in the NE and consists of the SUN1/2 proteins spanning the inner nuclear membrane and Nesprin proteins embedded in the outer membrane. The LINC complex, by interacting with both the nuclear lamina and the cytoskeleton, transmits mechanical forces to the nucleus regulating its morphology and functional homeostasis. In this study we show extensive alterations to the LINC complex in motor and cortical iPSC-derived neurons and spinal cord organoids carrying the ALS causative mutation in the C9ORF72 gene (C9). Importantly, we show that such alterations are present in vivo in a cohort of sporadic ALS and C9-ALS postmortem spinal cord and motor cortex specimens. We also found that LINC complex disruption strongly correlated with nuclear morphological alterations occurring in ALS neurons, independently of TDP43 mislocalization. Altogether, our data establish morphological and functional alterations to the LINC complex as important events in ALS pathogenic cascade, making this pathway a possible target for both biomarker and therapy development.
Immunohistochemistry is a widely used technique to visualize specific tissue structures as well as protein expression and localization. Two alternative approaches are widely used to handle the tissue ...sections during the staining procedure, one approach consists of mounting the sections directly on glass slides, while a second approach, the free-floating, allows for fixed sections to be maintained and stained while suspended in solution. Although slide-mounted and free-floating approaches may yield similar results, the free-floating technique allows for better antibody penetration and thus should be the method of choice when thicker sections are to be used for 3D reconstruction of the tissues, for example when the focus of the experiment is to gain information on dendritic and axonal projections in brain regions. In addition, since the sections are kept in solution, a single aliquot can easily accommodate 30 to 40 sections, handling of which is less laborious, particularly in large-scale biomedical studies. Here, we illustrate how to apply the free-floating method to fluorescent immunohistochemistry staining, with a major focus on brain sections. We will also discuss how the free-floating technique can easily be modified to fit the individual needs of researchers and adapted to other tissues as well as other histochemical-based stainings, such as hematoxylin and eosin and cresyl violet, as long as tissue samples are properly fixed, typically with paraformaldehyde or formalin.
With the increased use of technology, relaxation interventions are finding their way into technology devices like virtual reality head-mounted displays (VR HMDs). However, there is a lack of evidence ...on the efficacy of VR relaxation interventions to reduce anxiety in athletes and how that is portrayed in their movement patterns. The purpose of the current study was to examine how a VR relaxation intervention affected perceived anxiety levels and penalty kick performance of female soccer players. Thirteen female soccer players took five penalty kicks in baseline, stress-induced, and VR relaxation conditions. Perceived levels of anxiety, self-confidence, mental effort, heart rate (HR), accelerometry of the lumbar spine and thigh, and performance in each condition was obtained. Results indicated that the VR intervention significantly reduced cognitive anxiety and somatic anxiety from baseline (
= 0.002;
= 0.001) and stress (
< 0.001;
< 0.001) with large effect sizes (Kendall's
= 0.72; 0.83). VR significantly increased self-confidence from baseline (
= 0.002) and stress (
= 0.001) with a large effect size (Kendall's
= 0.71). Additionally, all participants felt that VR helped them relax. Mental effort was significantly higher in the stress condition compared to that in baseline (
= 0.007) with moderate effect size (Kendall's
= 0.39). Peak acceleration and performance were not significantly influenced by stress or VR. This study serves as an initial step to evaluate VR relaxation interventions on performance in female soccer players.
Lipodystrophy associated with human immunodeficiency virus infection causes abdominal fat gain, peripheral subcutaneous fat atrophy, insulin resistance, low levels of high-density lipoprotein ...cholesterol, and hypertriglyceridemia. An exercise program combined with a moderate-fat, low-glycemic-index, high-fiber diet can reverse several aspects of lipodystrophy, and, until specific treatment is available, should be considered for treatment of lipodystrophy.
Introduction
Primary postpartum haemorrhage causes approximately 25% of global maternal deaths and accounts for significant maternal morbidity. While high certainty evidence demonstrates that ...tranexamic acid reduces comparative blood loss in postpartum haemorrhage in hospital settings, limited data exist on the specific pharmacological management of this condition in out‐of‐hospital settings, and the implications for rural communities.
Objective
To determine the efficacy of oxytocin compared to tranexamic acid in women suffering postpartum haemorrhage in the out‐of‐hospital environment.
Design
A systematic review comparing evidence containing patients with postpartum haemorrhage in the out‐of‐hospital and/or rural setting, in which oxytocin/tranexamic acid were used. Outcome measures were comparative blood loss/haemorrhagic shock, the need for further interventions and maternal/neonatal morbidity/mortality.
Findings
No randomised control trials have been conducted in an out‐of‐hospital environment in relation to oxytocin/tranexamic acid. In this setting, there is no difference in outcome measures when using oxytocin compared to no intervention, or oxytocin compared to standard care. Data are lacking on the effect of tranexamic acid on the same outcome measures.
Discussion
Rural and out‐of‐hospital management of postpartum haemorrhage is limited by resource availability and practitioner availability, capacity and experience. In‐hospital evidence may lack transferability, therefore direct evidence on the efficacy of pharmacological management in these contexts is scant and requires redress.
Conclusion
There is no difference in blood loss, neonatal or maternal mortality or morbidity, or need for further interventions, when using oxytocin or TXA compared to no intervention, or compared to standard care, for PPH. Further studies are needed on the efficacy of these drugs, and alternate or co‐drug therapies, for PPH in the out‐of‐hospital environment and rural clinical practice.
To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure.
From the U.S. Zika Pregnancy and Infant Registry, a national surveillance ...system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively.
Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay.
Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families.
We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.
Abstract
Background
The clinical findings among children with postnatally acquired Zika virus disease are not well characterized. We describe and compare clinical signs and symptoms for children aged ...<18 years.
Methods
Zika virus disease cases were included if they met the national surveillance case definition, had illness onset in 2016 or 2017, resided in a participating state, and were reported to the Centers for Disease Control and Prevention. Pediatric cases were aged <18 years; congenital and perinatal infections were excluded. Pediatric cases were matched to adult cases (18‒49 years). Clinical information was compared between younger and older pediatric cases and between children and adults.
Results
A total of 141 pediatric Zika virus disease cases were identified; none experienced neurologic disease. Overall, 28 (20%) were treated in an emergency department, 1 (<1%) was hospitalized; none died. Of the 4 primary clinical signs and symptoms associated with Zika virus disease, 133 (94%) children had rash, 104 (74%) fever, 67 (48%) arthralgia, and 51 (36%) conjunctivitis. Fever, arthralgia, and myalgia were more common in older children (12‒17 years) than younger children (1‒11 years). Arthralgia, arthritis, edema, and myalgia were more common in adults compared to children.
Conclusions
This report supports previous findings that Zika virus disease is generally mild in children. The most common symptoms are similar to other childhood infections, and clinical findings and outcomes are similar to those in adults. Healthcare providers should consider a diagnosis of Zika virus infection in children with fever, rash, arthralgia, or conjunctivitis, who reside in or have traveled to an area where Zika virus transmission is occurring.
Zika virus disease in children is generally mild, and severe illnesses are unusual. The symptoms frequently reported among children with Zika virus disease are common to many childhood illnesses and are not notably different than those experienced by adults.
This paper traces an unfolding process of applying principles of organizational storytelling to build an unpublished website. I created this website to tell the story of a small nonprofit seeking to ...increase and continue its watershed restoration efforts. Storytelling has become a popular messaging approach within non-profit organizations. I conducted direct interviews with key members of the organization, then set selected excerpts within the context of a written meta-story that conveys information, delivers a call to action, and provides a means for visitor response. Site content corresponds to categories of narrative discourse designed to encourage active response from listeners. The site design employs techniques for capturing and maintaining visitor interaction. The paper includes theoretical discussion of organizational storytelling, non-profit messaging, and website building, as well as basic ideas for future launch and utilization of the website and additional applications of the audio recording files.
Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and ...optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance.
is a pathogen responsible for significant proportions of nosocomial and health care-associated infections and is known to acquire multiple antibiotic resistance genes. Here, we announce the full ...genome sequences of 12
bacteriophages from samples collected in wastewater treatment facilities across the western United States.
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