Central cholinergic dysfunction in the adult form of Niemann Pick disease type C: a further link with Alzheimer’s disease?

Adult patients with Niemann-Pick disease type C (NPC) usually develop cognitive impairment progressing to dementia, whose pathophysiology remains still unclear. Noteworthy parallels exist in cognitive impairment and cellular pathology of NPC and Alzheimer’s disease (AD). In particular, alterations of cholinergic system, which represent one of the pathological hallmarks and contribute to cognitive deterioration in AD, have recently been demonstrated in a human brain autopsy and in an experimental model of NPC. This finding raised the issue that central cholinergic circuits dysfunction may contribute to pathophysiology of cognitive impairment in NPC as well, and prompted us to evaluate the cholinergic functional involvement in NPC patients by applying a neurophysiologic technique, named short-latency afferent inhibition (SAI). We describe clinical, biochemical, molecular and neuropsychological features, and SAI findings in three patients affected by NPC. Diagnosis of NPC was assessed by molecular analysis of the NPC1 gene in all patients. In two of them, biochemical analysis of intracellular accumulation of unesterified cholesterol was also performed. The main clinical features were cerebellar ataxia, vertical supranuclear gaze palsy and a variable degree of cognitive impairment ranging from only memory impairment to severe dementia. Electrophysiological evaluation revealed a reduced SAI in all three patients. Our SAI findings provide evidence of cholinergic dysfunction in patients with the adult form of NPC, supporting that cholinergic alterations may play a role in cognitive impairment in NPC, and strengthening the similarities between NPC and AD.     

Current status of COVID-19 treatment: An opinion review

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development. Several drugs have been used for the management of coronavirus disease 2019 (COVID-19), which has affected many hospitals and health centers worldwide. Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality, as there are very few published randomized clinical trials. Despite this, the literature offers some material for study and reflection. This opinion review attempts to address three burning questions on COVID-19 treatment options. (1) What kind of studies are currently published or ongoing in the treatment of patients with COVID-19? (2) What drugs are currently described in the literature as options of treatment for patients affected by the infection? And (3) Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy? By answering these questions, we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo, and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.     

Anaglyph of Retinal Stem Cells And Developing Axons: Selective Volume Enhancement In Microscopy Images

Retinal stem cell culture has become a powerful research tool, but it requires reliable methods to obtain high‐quality images of living and fixed cells. This study describes a procedure for using phase contrast microscopy to obtain three‐dimensional (3‐D) images for the study of living cells by photographing a living cell in a culture dish from bottom to top, as well as a procedure to increase the quality of scanning electron micrographs and laser confocal images. The procedure may also be used to photograph clusters of neural stem cells, and retinal explants with vigorous axonal growth. In the case of scanning electron microscopy and laser confocal images, a Gaussian procedure is applied to the original images. The methodology allows for the creation of anaglyphs and video reconstructions, and provides high‐quality images for characterizing living cells or tissues, fixed cells or tissues, or organs observed with scanning electron and laser confocal microscopy. Its greatest advantage is that it is easy to obtain good results without expensive equipment. The procedure is fast, precise, simple, and offers a strategic tool for obtaining 3‐D reconstructions of cells and axons suitable for easily determining the orientation and polarity of a specimen. It also enables video reconstructions to be created, even of specimens parallel to the plastic base of a tissue culture dish, It is also helpful for studying the distribution and organization of living cells in a culture, as it provides the same powerful information as optical tomography, which most confocal microscopes cannot do on sterile living cells. Anat Rec, 297:770–780, 2014. © 2014 Wiley Periodicals, Inc.     

The changing profile of the patient undergoing coronary artery bypass surgery

The first 100 consecutive patients undergoing isolated coronary artery bypass surgery in 1975 were evaluated with respect to the incidence of operative risk factors and outcome. When compared with an identically selected group from 1985, there was significant worsening of the preoperative condition over the decade with regard to mean age (p less than 0.0005), presence of congestive heart failure (p less than 0.05), left ventricular dysfunction (p less than 0.05), severity of coronary artery disease (p less than 0.001) and incidence of emergency operation (p less than 0.05). More patients in 1985 had associated medical diseases such as diabetes (p less than 0.01) and chronic lung disease (p less than 0.005). There was an increase in the occurrence of vascular diseases (hypertension, renal dysfunction, peripheral vascular and cerebrovascular disease) (p less than 0.05). Overall operative mortality increased from 1 to 8% (p less than 0.05) over the decade. Despite the deterioration in the clinical profile of the patient undergoing coronary bypass surgery, elective procedures were still performed with low mortality. The significant increase in overall mortality was chiefly in patients undergoing emergency operation (p less than 0.05). There were also increases in operative morbidity including low output syndrome (p less than 0.01) and respiratory (p less than 0.005) and neurologic (p = 0.06) complications.     

Transcatheter occlusion of ruptured sinus of valsalva aneurysm: innovative use of available technology.

A 9-year-old boy was found to have ruptured sinus of Valsalva aneurysm (RSVA) and aortic coarctation. Following relief of aortic coarctation by balloon angioplasty, transcatheter coil occlusion of the RSVA was performed successfully under transesophageal echocardiographic and fluoroscopic monitoring; bioptome-assisted delivery of 0.052" Gianturco coil was undertaken via a 7 Fr sheath stabilized by an 0.035" guidewire passing through the RSVA and the sheath. This report details the technique of occlusion.     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.