ET-1 actions in the kidney: evidence for sex differences

Hypertension and chronic kidney disease are more common in men than in premenopausal women at the same age. In animal models, females are relatively protected against genetic or pharmacological procedures that produce high blood pressure and renal injury. Overactivation or dysfunction of the endothelin (ET) system modulates the progression of hypertension or kidney diseases with the ET_A receptor primarily mediating vasoconstriction, injury and anti-natriuresis, and ET_B receptors having opposite effects. The purpose of this review is to examine the role of the ET system in the kidney with a focus on the inequality between the sexes associated with the susceptibility to and progression of hypertension and kidney diseases. In most animal models, males have higher renal ET-1 mRNA expression, greater ET_A-mediated responses, including renal medullary vasoconstriction, and increased renal injury. These differences are reduced following gonadectomy suggesting a role for sex hormones, mainly testosterone. In contrast, females are relatively protected from high blood pressure and kidney damage via increased ET_B versus ET_A receptor function. Furthermore, ET_A receptors may have a favourable effect on sodium excretion and reducing renal damage in females. In human studies, the genetic polymorphisms of the ET system are more associated with hypertension and renal injury in women. However, the knowledge of sex differences in the efficacy or adverse events of ET_A antagonists in the treatment of hypertension and kidney disease is poorly described. Increased understanding how the ET system acts differently in the kidneys between sexes, especially with regard to receptor subtype function, could lead to better treatments for hypertension and renal disease.

LINKED ARTICLES

This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168.issue-1     

Biological markers that predict clinical recurrence in ductal carcinoma in situ of the breast

The optimal management of ductal carcinoma in situ (DCIS) is controversial, due in part to our poor understanding of its natural history. We undertook to identify subgroups of DCIS based on the expression of biomarkers, which were related to the likelihood of clinical recurrence. Biomarker expression of a total of 95 DCIS lesions in a nested case-control study within a population-based cohort with up to 135 months follow-up data (median 101 months) was analysed using immunohistochemistry. ERBB2-positivity and bcl-2-, oestrogen receptor (ER)- and progesterone receptor (PR)-negativity were individually associated with the risk of clinical recurrence. The predictive value of these biomarkers was independent of cytonuclear grade. ERBB2, bcl-2, ER and PR expression were conserved in the recurrent lesions, including subsequent invasive cancers. p21-positive DCIS was also associated with clinical recurrence, independently of the associations with ERBB2/bcl-2/ER/PR expression. These data identify clinically and biologically relevant subcategories of DCIS lesions, an essential basis for improving management.     

Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination

Background  

Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.     

Flammability and combustion hazard of preserved human tissues

Preservation techniques have evolved over the years to respond to the need of longer dissection periods, with formaldehyde being widely used for this purpose. In recent years, efforts have been focusing on reducing the health hazards of this fixative and the rigidity of the tissues embalmed with it. With every embalming technique that they are either developing or resurrecting from various protocols, institutions need to assess the fire and health hazards of all the chemicals being used. Compliance with the storage and handling safeguards listed in the Material Safety Data Sheet of each chemical, needs to be accompanied by infrastructure changes. To reduce the health hazards of formaldehyde, institutions are taking appropriate countermeasures directed at the source itself, by using substitutes or injecting formaldehyde chelating agents, and are adopting high performance air extraction systems to protect the users. However, little is known about the flammability risk of embalmed human bodies. During a recent visit to McGill University morgue by architects and safety inspectors to expand it, we were asked about the flammability risk of the embalmed specimens, so we carried out a flashpoint test to evaluate the flammability potential of specimens embalmed with each of our three embalming techniques: formaldehyde-based, Thiel, and phenol-based. With the phenol-based embalming showing the most risks, attention should be drawn to all institutions who are experimenting with various embalming techniques to evaluate the flammability potential of their embalmed specimens.     

Promoting and achieving excellence in the delivery of Integrated Allergy Care: the European Academy of Allergy & Clinical Immunology competencies for allied health professionals working in allergy

The multi-disciplinary team approach is an effective model for patient care. Allied health professionals (AHPs) are an important part of such teams, bringing specific knowledge and skills related to the target patient population. The AHPs most often involved in allergy care are nurses and dietitians. Nurses are often involved in the care of patients with all types of allergy and also with asthma, whilst allergy-specialist dietitians provide vital nutritional and dietary support for the diagnosis and management of food allergy. There are many other AHPs who have a role to play in allergy care, including physiotherapists, psychologists, pharmacists and speech therapists, and their involvement is likely to develop as allergy care becomes more rooted in the community. With the development of multi-professional teams comes the requirement for disease-specific knowledge and skill sets, with all allergy team members required to have baseline knowledge and competency of the condition being managed. Whilst some competencies for AHPs practising in other disease states have been published, none are available for allergic disease against which AHPs can be benchmarked. The European Academy of Allergy & Clinical Immunology (EAACI) recognised this need, and supported the establishment of a Task Force to develop allergy-focussed competencies for AHPs. The varied skills, expertise and professional background of the Task Force members enabled the creation of a set of allergy competencies relevant to all AHPs working in allergy. It is recognised that the training and allergy expertise of AHPs, and their role within the allergy setting, will vary considerably depending on the country. However, it is important for patient care, that all AHP involved in allergy services have access to training, of a sufficiently high enough level to be aspirational and enable the continued growth and development of a wide range of allergy services, given the increasing need. The EAACI competencies will provide an important benchmark for allergy knowledge and skills against which education and training can be designed and health care professionals can subsequently be measured. However, more importantly, the EAACI AHP allergy competencies will enable the development and reach of specialist allergy services, with allergy-specialist AHPs undertaking key roles, especially in the community care setting.     

Novel digital forensic readiness technique in the cloud environment

This paper examines the design and implementation of a feasible technique for performing Digital Forensic Readiness (DFR) in cloud computing environments. The approach employs a modified obfuscated Non-Malicious Botnet (NMB) whose functionality operates as a distributed forensic Agent-Based Solution (ABS) in a cloud environment with capabilities of performing forensic logging for DFR purposes. Under basic Service Level Agreements (SLAs), this proactive technique allows any organization to perform DFR in the cloud without interfering with operations and functionalities of the existing cloud architecture or infrastructure and the collected file metadata. Based on the evaluation discussed, the effectiveness of our approach is presented as the easiest way of conducting DFR in the cloud environment as stipulated in the ISO/IEC 27043: 2015 international standard, which is a standard of information technology, security techniques and incident investigation principles and processes. Through this technique, digital forensic analysts are able to maximize the potential use of digital evidence while minimizing the cost of conducting DFR. As a result of this process, the time and cost needed to conduct a Digital Forensic Investigation (DFI) is saved. As a consequence, the technique helps the law enforcement, forensic analysts and Digital Forensic Investigators (DFIs) during post-event response and in a court of law to develop a hypothesis in order to prove or disprove a fact during an investigative process, if there is an occurrence of a security incident. Experimental results of the developed prototype are described which conclude that the technique is effective in improving the planning and preparation of pre-incident detection during digital crime investigations. In spite of that, a comparison with other existing forensic readiness models has been conducted to show the effectiveness of the previously proposed Cloud Forensic Readiness as a Service (CFRaaS) model.     

Phantom pain: A sensitivity analysis

Purpose:?To analyse how decisions to dichotomise the frequency and impediment of phantom pain into absent and present influence the outcome of studies by performing a sensitivity analysis on an existing database.

Method:?Five hundred and thirty-six subjects were recruited from the database of an orthopaedic workshop and filled out a questionnaire in which the following items were assessed: demographics, side, date, level and reason of amputation, presence and frequency of phantom sensations, phantom pain and stump pain, and impediment due to phantom pain.

Results:?The prevalence of phantom pain ranged from 7?–?72% when different cut off points for the frequency of phantom pain were applied. The significance of the various risk factors for the prevalence of phantom pain changed when different cut off points were applied. Only stump pain and phantom sensations were significant risk factors for all cut off points. Risk factors for the impediment of phantom pain changed when different cut off points were applied and these risk factors were different from those for the prevalence of phantom pain.

Conclusion:?The choice of cut off points influences the outcome of phantom pain studies considerably. This study provides some insight into the differences in prevalence and risk factors found in literature.     

Shuni Virus in Cases of Neurologic Disease in Humans,South Africa

We describe Shuni virus (SHUV) detection in human neurologic disease cases in South Africa. SHUV RNA was identified in 5% of cerebrospinal fluid specimens collected during the arbovirus season from public sector hospitals. This finding suggests that SHUV may be a previously unrecognized cause of human neurologic infections in Africa.