Neuropathological substrates of dementia and depression in vascular dementia, with a particular focus on cases with small infarct volumes

The neuropathological substrates of dementia and depression were evaluated in 30 patients with cerebrovascular disease and significant cognitive impairment (VaD), with a particular focus on patients with small infarct volumes (<15 ml). VaD patients with small infarct volumes had a similar degree of cognitive impairment to those with larger infarct volumes (>15 ml) but were significantly more likely to be depressed and to have areas of microinfarction. A review of individual cases with small infarct volumes suggested that the combination of microinfarction, diffuse white matter disease and perivascular changes, or the overlap of neurodegenerative pathologies and microvascular changes were particularly important. Microinfarction was also significantly associated with major depression.     

Extracorporeal techniques in thoracoabdominal aortic surgery

Most complications related to thoracoabdominal aortic reconstruction stem from ischemia-induced injury to the viscera, kidneys, and spinal cord. In addition to adjunctive methods designed to minimize metabolic demands of the spinal cord during aortic cross-clamping, a variety of extracorporeal techniques have been developed that provide supplemental blood flow to vital end organs during the period of clamp-induced ischemia. These techniques represent a broad range of design complexities and command significant operator expertise to optimize their benefit. This section briefly describes commonly used extracorporeal circulation methods in thoracoabdominal aortic surgery.     

Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design

Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein’s ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target.     

Proteasome inhibition leads to early loss of synaptic proteins in neuronal culture

A dysfunctional ubiquitin proteasome system may be a mediating factor of disease progression in Lewy body dementia (LBD). The effects of proteasome inhibition using lactacystin and epoxomicin in primary neuronal culture were studied to assess the validity of this model to reflect the cortical pathology of LBD. Treatment of primary cortical neurons with 5???M lactacystin for 24?h led to a 38?% reduction in the levels of ??-III-tubulin (p?<?0.05), a 48?% reduction in the levels of synaptophysin (p?<?0.05) and a 74?% reduction in the levels of drebrin (p?<?0.01), when compared to controls. Results for epoxomicin were similar. The loss of neuronal protein occurred prior to any loss of mitochondrial activity or cell death. The results are reflective of the loss of synapses and the synaptic changes observed in LBD, which may be an early event in the neurodegeneration of LBD. The similarities with the pathological changes in LBD highlight the possibility that this model can potentially provide a platform to test novel treatments.     

Analgesic treatments in people with dementia - how safe are they? A systematic review

Introduction: People with dementia may be unable to verbally express pain and suffer from untreated pain. Use of analgesics in people with dementia has increased during the last decade, in particular opioid analgesics with high potential for adverse effects.

Areas covered: This article presents a systematic review of the current evidence for safety and tolerability of analgesic drugs from randomized controlled trials in people with dementia. Relevant trials were identified by a literature search in the EMBASE, MEDLINE, and Cochrane databases from inception to November 2018. The search included the main terms ‘dementia’ and ‘analgesic’ or their subterms, and was filtered to limit results to clinical trials.

Expert opinion: Although pain treatment is increasingly recognized as an important clinical issue in people with advanced dementia, there is currently a lack of evidence to support safety evaluations of commonly used analgesics in this group. To inform treatment decisions and enable care providers to appropriately monitor patients at risk of adverse effects, it is necessary to conduct well-designed clinical trials to investigate the relative efficacy and safety of analgesics in people with dementia, with particular emphasis on harmful effects of long-term opioid use as well as short-term use of nonsteroidal anti-inflammatory drugs.     

Reconceptualizing the Domain and Boundaries of Family Life Education

Many scholars have defined family life education (FLE), and some have differentiated it from other family‐related fields. For example, Doherty (1995) provided a definition of the boundaries between FLE and family therapy; however, we believe those criteria can be improved. We explore the professions of family life education, family therapy, and family case management using the questions why, what, when, for whom, and how? After examining these questions for each role, we introduce the domains of family practice to differentiate among them. The approach defines FLE and encourages appropriate collaboration among the fields. Suggestions are made for using this model for career exploration, reviewing job requirements to assess role consistency and clarity, and for determining the need for and appropriateness of referral and collaboration.     

Compliance with the recommendations of medical consultants

Compliance with the consultant’s recommendations is one measure of the effectiveness of a consultation. A previous study showed that compliance was better when fewer recommendations were made. In the subsequent year, consultants were encouraged to limit their recommendations to five or fewer. Despite a significant decrease in the number of recommendations, compliance rates remained essentially unchanged (72%). Multivariate analysis demonstrated that the clinical severity of the patient’s disease and the number of associated problems, as well as the types of recommendations, were significant predictors of compliance. Compliance was best for recommendations involving medications (84%) and worst for recommendations involving diagnostic tests (62%). Compliance was also evaluated in the context of a surgeon’s view of the appropriateness of the recommendations. For recommendations felt to be essential to patient care the compliance rate was 75%, but it was only 44% for recommendations judged non-essential (p<0.001). The consulting internist should be aware that the surgeon’s view of the relevance of the recommendations to patient care needs may have an important effect on compliance. Received from the Departments of Medicine and Surgery, Cornell University Medical College, New York, New York. Dr. Ballard was a Henry J. Kaiser Foundation Fellow in General Internal Medicine. Dr. Gold is a Fellow in Cardio-Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Dr. Charlson is a Henry J. Kaiser Family Foundation Faculty Scholar in General Internal Medicine.