Astrocytes and NG2‐glia: what's in a name?

Classic studies recognize two functionally segregated macroglial cell types in the central nervous system (CNS), namely astrocytes and oligodendrocytes. A third macroglial cell type has now been identified by its specific expression of the NG2 chondroitin sulphate proteoglycan (NG2-glia). These NG2-glia exist abundantly in both grey and white matter of the mature CNS and are almost as numerous as astrocytes. It is well established that NG2-glia give rise to oligodendrocytes. However, the majority of NG2-glia in the adult CNS proliferate very slowly and are non-motile. Both astrocytes and NG2-glia display a stellate morphology and express ion channels and receptors to neurotransmitters used by neurons. Both types of glia make intimate contacts with neurons in grey and white matter, and their functional differences and similarities are only beginning to be unravelled. Recent observations emphasize the need to examine the relationship between astrocytes and NG2-glia, and address the question of whether they represent overlapping or two distinct glial cell populations. To be of any relevance, this classification must relate to specific functions in the neural network. At present, the balance of evidence is that NG2-glia and astrocytes are functionally segregated populations.     

Towards enhancing national capacity for evidence informed policy and practice in falls management: a role for a "Translation Task Group"?

Background

There has been a growing interest over recent years, both within Australia and overseas, in enhancing the translation of research into policy and practice. As one mechanism to improve the dissemination and uptake of falls research into policy and practice and to foster the development of policy-appropriate research, a "Falls Translation Task Group" was formed as part of an NHMRC Population Health Capacity Building grant. This paper reports on the group's first initiative to address issues around the research to policy and practice interface, and identifies a continuing role for such a group.

Methods

A one day forum brought together falls researchers and decision-makers from across the nation to facilitate linkage and exchange. Observations of the day's proceedings were made by the authors. Participants were asked to complete a questionnaire at the commencement of the forum (to ascertain expectations) and at its completion (to evaluate the event). Observer notes and the questionnaire responses form the basis of analysis.

Results

Both researchers and decision-makers have a desire to bridge the gap between research and policy and practice. Significant barriers to research uptake were highlighted and included both "health system barriers" (for example, a lack of financial and human resources) as well as "evidence barriers" (such as insufficient economic data and implementation research). Solutions to some of these barriers included the identification of clinical champions within the health sector to enhance evidence uptake, and the sourcing of alternative funding to support implementation research and encourage partnerships between researchers, decision-makers and other stakeholders.

Conclusion

Participants sought opportunities for ongoing networking and collaboration. Two activities have been identified as priorities: establishing a "policy-sensitive" research agenda and partnering researchers and decision-makers in the process; and establishing a National Translation Task Group with a broad membership.

     

Dimethyl amiloride,a Na<Superscript>+</Superscript>–H<Superscript>+</Superscript> exchange inhibitor,and its cardioprotective effects in hemorrhagic shock in in vivo resuscitated rats

Stimulation of the Na⁺–H⁺ exchanger plays an important role in the pathway of myocardial dysfunction and injury following hemorrhagic shock. Inhibition of the Na⁺–H⁺ exchanger appears to be a new pharmacological tool for myocardial protection. Despite the extensive research that has been done on the role of the Na⁺–H⁺ exchanger in ischemia reperfusion, little is known about the role of the exchanger following hemorrhagic shock. The purpose of this study was to examine the protective effects of blocking the cardiac Na⁺–H⁺ exchanger, using 20 μM dimethyl amiloride (DMA), a specific Na⁺–H⁺ exchanger blocker, on myocardial contractile function after ex vivo perfusion of isolated rat heart following 1 h of hemorrhagic shock. Sprague–Dawley rats were assigned to hemorrhage + DMA, hemorrhage, sham hemorrhage + DMA and sham hemorrhage groups (n = 6 per group). Hearts were perfused with a balanced salt solution for 60 min. In the DMA treated group, 20 μM DMA was added for the first 5 min of the 60-min ex vivo heart resuscitation. The results showed that inhibition of the Na⁺–H⁺ exchanger for 5 min on ex vivo perfusion of the isolated hearts following hemorrhagic shock using 20 μM DMA improved myocardial contractile function. Blocking the Na⁺–H⁺ exchanger on ex vivo perfusion of isolated hearts using 20 μM DMA has protective effects on myocardial contractile function.     

Medical education in a foreign language and history-taking in the native language in Lebanon – a nationwide survey

Background

With the adoption of the English language in medical education, a gap in clinical communication may develop in countries where the native language is different from the language of medical education. This study investigates the association between medical education in a foreign language and students’ confidence in their history-taking skills in their native language.

Methods

This cross-sectional study consisted of a 17-question survey among medical students in clinical clerkships of Lebanese medical schools. The relationship between the language of medical education and confidence in conducting a medical history in Arabic (the native language) was evaluated (n?=?457).

Results

The majority (88.5%) of students whose native language was Arabic were confident they could conduct a medical history in Arabic. Among participants enrolled in the first clinical year, high confidence in Arabic history-taking was independently associated with Arabic being the native language and with conducting medical history in Arabic either in the pre-clinical years or during extracurricular activities. Among students in their second clinical year, however, these factors were not associated with confidence levels.

Conclusions

Despite having their medical education in a foreign language, the majority of students in Lebanese medical schools are confident in conducting a medical history in their native language.

     

Four dermatomyositis-specific autoantibodies—anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5—in adult and juvenile patients with idiopathic inflammatory myopathies in a Hungarian cohort

Idiopathic inflammatory myopathies (IIMs) are chronic systemic autoimmune diseases characterised by symmetrical, proximal muscle weakness. Dermatomyositis represents one subset of IIMs, in which skin rashes are present in addition to muscle weakness. Myositis-specific antibodies can only be detected in myositis, and they are directed against specific proteins found in the cytoplasm or in the nucleus of cells. With this case-based article, we introduce the recently detected anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5 antibodies that form various clinical groups. These antibodies could be detected in patients with dermatomyositis. The myositis-specific autoantibodies of three hundred and thirty-seven Hungarian patients with IIM were detected. Retrospective analysis of the clinical findings has also been introduced by revision of the medical history. We had twelve patients with anti-TIF1γ positivity, four patients with anti-NXP2 positivity and four patients with anti-SAE positivity. We did not have any positive anti-MDA5 patients. The most relevant clinical findings were similar to those seen in previously published reports. Eleven of the twelve patients with anti-TIF1γ positivity had classical dermatomyositis. Three of the twelve anti-TIF1γ patients had cancer during the disease progression. This was two out of four for the anti-NXP2 subgroup and one in four for the anti-SAE subgroup. In two juvenile dermatomyositis cases, typical ulceration was seen in patients with anti-TIF1γ positivity. The frequency of pulmonary fibrosis during the disease progression was 2/12, 1/4 and 1/4 in anti-TIF1γ, anti-NXP2 and anti-SAE, respectively. Other extra-muscular manifestations, such as arthralgia, dysphagia, dysphonia and dyspnoea, were also detectable. The myositis subgroups determined by these myositis-specific autoantibodies differ from each other in their symptoms, prognosis and therapy responsiveness. Their detection is helpful for the preparation of an adequate treatment, but in daily diagnostic methods, these antibodies cannot be detected. By presenting our anti-TIF1γ, anti-NXP2 and anti-SAE cases, we would like to highlight the clinical role of these antibodies.     

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient – Case report and review of literature

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.     

Immunohistochemical and mutational analysis of PDGF and PDGFR in desmoid tumours: is there a role for tyrosine kinase inhibitors in c‐kit‐negative desmoid tumours?

AIM: To determine the platelet-derived growth factor (PDGF) alpha and beta status of desmoid tumours. Desmoid tumours are rare monoclonal neoplasms that appear to have no metastatic potential. Surgical resection and radiotherapy in the event of a positive surgical margin is the first-line treatment. Recurrences are frequent. Treatment results using non-steroidal anti-inflammatory agents, anti-oestrogen compounds and other agents such as Imatinib mesylate have been published. Therapy with Imatinib has been proposed as a therapeutic option, although in most reports desmoid tumours are reported to be c-kit-. METHODS AND RESULTS: We performed immunohistochemical analysis on 124 archived samples (85 patients) of desmoid tumours using antibodies to PDGFalpha, PDGFbeta, PDGFRalpha and PDGFRbeta. All desmoid tumours showed immunoreactivity with antibodies to PDGFalpha and PDGFRalpha, whereas with antibodies to PDGFbeta and PDGFRbeta no specific reaction could be detected. Mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) on frozen material from 14 patients was performed, but no mutations leading to amino acid changes in the mature protein were identified. CONCLUSION: The absence of an activating mutation in a protooncogene does not exclude the efficacy of tyrosine kinase inhibitors through other possible mechanisms, and these might be a therapeutic option for patients with desmoid tumours in whom established local and systemic approaches fail to control the disease.     

TGFβ—a role in systemic sclerosis?

Systemic sclerosis (SSc) is a multisystem connective tissue disorder in which there is progressive fibrosis. Transforming growth factor beta (TGFβ) has wide-ranging cellular actions. It is a potent chemoattractant for human dermal fibroblasts, from which it may induce synthesis of collagen, which suggests that it may have a central role to play in the pathogenesis of SSc. This is supported to some extent by in vitro studies. SSc fibroblasts produce more collagens and fibronectin than normal fibroblasts and elevated TIMP levels have been observed, all of which could be explained on the basis of TGFβ stimulation of fibroblasts. Some studies have suggested that fibroblasts are the source of TGFβ. However, the serum of patients with SSc is cytotoxic to endothelial cells, which could culminate in TGFβ synthesis by them, with secondary fibroblast stimulation. The role of TGFβ remains elusive, although it would seem an ideal candidate as a mediator of fibrosis in systemic sclerosis. © 1998 John Wiley & Sons, Ltd.     

Shattered and stitched chromosomes—chromothripsis and chromoanasynthesis—manifestations of a new chromosome crisis?

Chromothripsis (chromosome shattering) has been described as complex rearrangements affecting single chromosome(s) in one catastrophic event. The chromosomes would be “shattered” and “stitched together” during this event. This phenomenon is proposed to constitute the basis for complex chromosomal rearrangements seen in 2‐3% of all cancers and in ～ 25% of bone cancers. Here we discuss chromothripsis, the use of this term and the evidence presented to support a single catastrophic event that remodels the genome in one step. We discuss why care should be taken in using the term chromothripsis and what evidence is lacking to support its use while describing complex rearrangements. © 2012 Wiley Periodicals, Inc.     

<Emphasis Type="Italic">RET</Emphasis> polymorphisms and the risk of Hirschsprung’s disease in a Chinese population

Hirschsprung's disease (HSCR) is a congenital disorder characterized by intestinal obstructions due to the absence of enteric ganglia along variable lengths of the intestinal tract. RET coding mutations have been found in approximately 50% of familial cases, but they only explain a minority of sporadic cases. Here, we report our investigation of a possible role of RET non-coding mutations in sporadic HSCR patients. The haplotypes of seven single nucleotide polymorphisms (SNPs), all located in a region 4 kb upstream of the gene through to 23 kb of intron 1, and one SNP in exon 2 were constructed in 125 Han Chinese patients with sporadic HSCR and in 148 Han Chinese controls. Our results indicated that eight SNPs were significantly associated with HSCR (P < 0.0001). The C allele of rs2505535 would appear to represent a protecting allele for the Chinese population. One single haplotype composed of these eight markers was present in 59.6% of patients, versus 18.1% of controls. Based on our results, we conclude that non-coding mutations in RET have important roles in the development of HSCR. The unknown functional disease variant(s), with a dosage-dependent effect in HSCR, is likely to be located in the 5'-region of the RET gene.     

Melatonin and the metabolic syndrome: a tool for effective therapy in obesity‐associated abnormalities?

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities associated with increased risk for cardiovascular diseases. Apart from its powerful antioxidant properties, the pineal gland hormone melatonin has recently attracted the interest of various investigators as a multifunctional molecule. Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischaemic heart disease and hypertension. However, its role in cardiovascular risk factors including obesity and other related metabolic abnormalities is not yet established, particularly in humans. New emerging data show that melatonin may play an important role in body weight regulation and energy metabolism. This review will address the role of melatonin in the MetS focusing on its effects in obesity, insulin resistance and leptin resistance. The overall findings suggest that melatonin should be exploited as a therapeutic tool to prevent or reverse the harmful effects of obesity and its related metabolic disorders.     

Thoracic and abdominal mesothelioma in a dog: a cytologist��s view

Mesothelioma is an uncommon tumour in dogs, whose diagnosis can be a challenge to the veterinary cytologist. This paper aims to report a case of mesothelioma in a dog, obtained from the cytological analysis of pleural and abdominal fluid, which allowed an in vivo diagnosis. A 4.10-year-old-boxer dog was presented for clinical care with abdominal distension, difficulty in breathing and loss of appetite. Laboratorial and imaging tests were performed, and the cytology of abdominal and pleural effusions suggested the presence of mesothelioma. The cytology was ratified later by a histopathology of the lungs, ovaries, liver, spleen, peritoneum and omentum.     

Array-CGH detection of a de novo 2.8 Mb deletion in 2q24.2→q24.3 in a girl with autistic features and developmental delay

We report a 3 years and 4 months old girl with autistic features, developmental delay, mental retardation, language impairment and dysmorphic features, carrying a 2.8 Mb de novo deletion of chromosome 2q24.2→q24.3 detected by array-CGH. This region contains two neuronal voltage-gated sodium channel genes SCN2A and SCN3A.     

Telling “the truth” in dementia-Do attitude and approach of general practitioners and specialists differ?

OBJECTIVE: The prevailing opinion in the literature that disclosing the diagnosis of dementia to patients is important is not always put into practice. The purpose of this study was to investigate differences between GPs and specialists (neurologists and psychiatrists) in the German ambulatory care system concerning the disclosure of the diagnosis of dementia. METHODS: Thirty in depth interviews with randomly selected GPs were conducted. On this basis a standardised questionnaire was developed and sent to 389 GPs and 239 neurologists and psychiatrists. RESULTS: The postal survey revealed only minor differences between GPs and specialists, both groups being equally in favour of a timely disclosure. For example, 70% of the GPs and 77% of the specialists strongly agreed that "patients with dementia should be informed early because of the possibility to plan their lives". This positive attitude is pronounced among younger physicians, but is somewhat contradicted by difficulties in the communication with patients expressed in the interviews. In the interviews, what may be described as a "double taboo" emerges, in that GPs describe taboo topic areas related to dementia for them and for their patients. CONCLUSION: The postal survey shows the two professional groups to be very much in favour of a timely disclosure--an attitude that is pronounced among younger physicians. These findings can be interpreted as a recent change of attitudes regarding the disclosure of the diagnosis of dementia in the medical profession. PRACTICE IMPLICATIONS: Training opportunities are needed in order to overcome communication obstacles in the doctor-patient-communication about dementia.