Toward a Shared Vision for Cancer Genomic Data Grossman, Robert L; Heath, Allison P; Ferretti, Vincent ...
The New England journal of medicine,
2016-Sep-22, Volume:
375, Issue:
12
Journal Article
Neonatal sepsis: an international perspective Vergnano, S; Sharland, M; Kazembe, P ...
Archives of Disease in Childhood. Fetal and Neonatal Edition,
05/2005, Volume:
90, Issue:
3
Journal Article, Book Review
Peer reviewed
Open access
Neonatal infections currently cause about 1.6 million deaths annually in developing countries. Sepsis and meningitis are responsible for most of these deaths. Resistance to commonly used antibiotics ...is emerging and constitutes an important problem world wide. To reduce global neonatal mortality, strategies of proven efficacy, such as hand washing, barrier nursing, restriction of antibiotic use, and rationalisation of admission to neonatal units, need to be implemented. Different approaches require further research.
Astrocytes have essential roles in the central nervous system and are also implicated in the pathogenesis of neurodegenerative disease. Forming non‐overlapping domains, astrocytes are highly complex ...cells. Immunohistochemistry to a variety of proteins can be used to study astrocytes in tissue, labelling different cellular components and sub‐populations, including glial fibrillary acidic protein, ALDH1L1, CD44, NDRG2 and amino acid transporters, but none of these labels the entire astrocyte population. Increasing heterogeneity is recognized in the astrocyte population, a complexity that is relevant both to their normal function and pathogenic roles. They are involved in neuronal support, as active components of the tripartite synapse and in cell interactions within the neurovascular unit (NVU), where they are essential for blood–brain barrier maintenance and neurovascular coupling. Astrocytes change with age, and their responses may modulate the cellular effects of neurodegenerative pathologies, which alone do not explain all of the variance in statistical models of neurodegenerative dementias. Astrocytes respond to both the neurofibrillary tangles and plaques of Alzheimer's disease, to hyperphosphorylated tau and Aβ, eliciting an effect which may be neuroprotective or deleterious. Not only astrocyte hypertrophy, in the form of gliosis, occurs, but also astrocyte injury and atrophy. Loss of normal astrocyte functions may contribute to reduced support for neurones and dysfunction of the NVU. Understanding how astrocytes contribute to dementia requires an understanding of the underlying heterogeneity of astrocyte populations, and the complexity of their responses to pathology. Enhancing the supportive and neuroprotective components of the astrocyte response has potential translational applications in therapeutic approaches to dementia.
This review provides a broad overview of the role of astrocytic populations in the healthy brain and their role in ageing and neurodegenerative diseases with an emphasis on Alzheimer's disease. Perturbation of astrocyte function may contribute to the pathogenesis of dementia and may present an additional therapeutic target.
Background:
Femoroacetabular impingement (FAI) is a well-known cause of hip pain in adolescents and young adults. However, the incidence in the general population has not been clearly defined.
...Purpose:
To (1) define the population-based incidence of diagnosis of FAI in patients with hip pain, (2) report the trends in diagnosis of FAI over time, and (3) determine the changes in the rate and type of surgical management over time.
Study Design:
Cohort study; Level of evidence, 3.
Methods:
A geographic database was used to identify patients who were 14 to 50 years old with hip pain between the years 2000 and 2016. Chart and radiographic review was performed to determine which patients had FAI. To be included, patients had to have a triad of clinical symptoms, physical examination signs, and imaging findings consistent with FAI. Medical records were reviewed to obtain demographic information, clinical history, physical examination findings, imaging details, and treatment details. Statistical analysis determined the overall age- and sex-adjusted annual incidence of FAI diagnosis and trends over time.
Results:
There were 1893 patients evaluated with hip pain, and 716 (38%; 813 hips) had diagnosed FAI. The mean ± SD age was 27.2 ± 8.4 years, and 67% were female. The incidence of FAI diagnosis was 54.4 per 100,000 person-years. Female patients had a higher incidence than male patients (73.2 vs 36.1 per 100,000 person-years; P < .01). Incidence of FAI diagnosis were higher from 2010 to 2016 (72.6 per 100,000 person-years; P < .01) as compared with 2005 to 2009 (45.3) and 2000 to 2004 (40.3). Hip arthroscopy, surgical hip dislocation, and periacetabular osteotomy utilization increased from the 2000-2004 to 2010-2016 periods, respectively: 1 (1%) to 160 (20%; P = .04), 2 (1%) to 37 (5%; P = .01), and 1 (1%) to 22 (3%; P = .58).
Conclusion:
The overall incidence of FAI diagnosis was 54.4 per 100,000 person-years, and it consistently increased between 2000 and 2016. Female patients had a higher incidence than male patients. The utilization of joint preservation operations, including hip arthroscopy, surgical hip dislocation, and anteverting periacetabular osteotomy, increased over time.
Aims
While vascular pathology is a common feature of a range of neurodegenerative diseases, we hypothesized that vascular changes occur in association with normal ageing. Therefore, we aimed to ...characterize age‐associated changes in the blood–brain barrier (BBB) in human and mouse cohorts.
Methods
Immunohistochemistry and Evans blue assays were used to characterize BBB dysfunction (tight junction protein expression and serum plasma protein accumulation), vascular pathology (pericyte loss and vascular density) and glial pathology (astrocyte and microglial density) in ageing neurological control human prefrontal cortex (a total of 23 cases from 5 age groups representing the spectrum of young adult to old age: 20–30 years, 31–45 years, 46–60 years, 61–75 years and 75+) and C57BL/6 mice (3 months, 12 months, 18 months and 24 months, n = 5/6 per group).
Results
Quantification of the tight junction protein ZO‐1 within the cortex and cerebellum of the mouse cohort showed a significant trend to both increased number (cortex P < 0.001, cerebellum P < 0.001) and length (cortex P < 0.001, cerebellum P < 0.001) of junctional breaks associated with increasing age. GFAP expression significantly correlated with ageing in the mice (P = 0.037). In the human cohort, assessment of human protein accumulation (albumin, fibrinogen and human IgG) demonstrated cells morphologically resembling clasmatodendritic astrocytes, indicative of BBB dysfunction. Semiquantitative assessment of astrogliosis in the cortex expression revealed an association with age (P = 0.003), while no age‐associated changes in microglial pathology, microvascular density or pericyte coverage were detected.
Conclusions
This study demonstrates BBB dysfunction in normal brain ageing, both in human and mouse cohorts.
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