Periocular rejuvenation using a unique non-ablative long-pulse 2940 nm Er:YAG laser

Lasers in Medical Science - The periocular region is challenging for cosmetic laser surgeons. Surgery and laser resurfacing have traditionally been used to correct periorbital lines and wrinkles....     

Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission

The efficacy of synaptic inhibition depends on the number of gamma-aminobutyric acid type A receptors (GABA(A)Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA(A)R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA(A)R beta subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the beta3 subunit) incorporates the major sites of serine phosphorylation within receptor beta subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepbeta3) corresponding to the AP2 binding motif in the GABA(A)R beta3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepbeta3 peptide, but not its phosphorylated equivalent (pepbeta3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA(A)R current. These effects of pepbeta3 on GABA(A)R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepbeta3 on GABA(A)R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA(A)Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.     

High rate of ventricular septal defects in WKY rats

In 1979, we first reported occurrence of biventricular hypertrophy in the original normotensive Wistar-Kyoto (WKY) strain obtained from the National Heart, Lung, and Blood Institute, which was derived directly from the Kyoto laboratory of Okamoto. At that time, we recommended that both ventricles be weighted when WKY are studied so that invalid conclusions are not made. Because no paper confirmed these findings for almost 20 years, heart weights were reported in only a few WKY studies, and the cause of this biventricular hypertrophy remained unknown, we re-evaluated this problem in commercially available rats. We, therefore, investigated WKY rats using transthoracic echocardiography to define the congenital heart defect. Up to 28% of commercially available WKY rats demonstrated severe congenital cardiac abnormalities associated with biventricular hypertrophy. Ventricular septal defect with pulmonary regurgitation was the most commonly encountered cardiac defect; other abnormalities included patent ductus arteriosus, and valvular defects. Pathologic and invasive hemodynamic studies confirmed these echocardiographic findings. Because this defect occurs in a large number of WKY rats obtained commercially from 2 different sources, investigators using this strain must carefully measure both ventricular weights to be certain that inappropriate and invalid conclusions are not derived therefrom.     

Factors associated with COVID‐19 related hospitalisation,critical care admission and mortality using linked primary and secondary care data

BackgroundIt is important that population cohorts at increased risk of hospitalisation and death following a COVID‐19 infection are identified and protected.ObjectivesWe identified risk factors associated with increased risk of hospitalisation, intensive care unit (ICU) admission and mortality in inner North East London (NEL) during the first UK COVID‐19 wave.MethodsMultivariate logistic regression analysis on linked primary and secondary care data from people aged 16 or older with confirmed COVID‐19 infection between 01/02/2020 and 30/06/2020 determined odds ratios (OR), 95% confidence intervals (CI) and P‐values for the association between demographic, deprivation and clinical factors with COVID‐19 hospitalisation, ICU admission and mortality.ResultsOver the study period, 1781 people were diagnosed with COVID‐19, of whom 1195 (67%) were hospitalised, 152 (9%) admitted to ICU and 400 (23%) died. Results confirm previously identified risk factors: being male, or of Black or Asian ethnicity, or aged over 50. Obesity, type 2 diabetes and chronic kidney disease (CKD) increased the risk of hospitalisation. Obesity increased the risk of being admitted to ICU. Underlying CKD, stroke and dementia increased the risk of death. Having learning disabilities was strongly associated with increased risk of death (OR = 4.75, 95% CI = [1.91, 11.84], P = .001). Having three or four co‐morbidities increased the risk of hospitalisation (OR = 2.34, 95% CI = [1.55, 3.54], P < .001; OR = 2.40, 95% CI = [1.55, 3.73], P < .001 respectively) and death (OR = 2.61, 95% CI = [1.59, 4.28], P < .001; OR = 4.07, 95% CI = [2.48, 6.69], P < .001 respectively).ConclusionsWe confirm that age, sex, ethnicity, obesity, CKD and diabetes are important determinants of risk of COVID‐19 hospitalisation or death. For the first time, we also identify people with learning disabilities and multi‐morbidity as additional patient cohorts that need to be actively protected during COVID‐19 waves.     

Factors related to patient satisfaction with complete denture therapy

BACKGROUND: Except for denture quality, many other factors are related to a patient's satisfaction with complete dentures (CDs). METHODS: A total of 222 patients with CDs took a part in this study. A questionnaire divided into 3 parts was completed by both the patients and the dentist, independently. The patients rated their dentures using a scale ranging from 1 to 5 (1 = dissatisfaction to 5 = excellent), and a dentist rated the quality of the denture and the denture-bearing area. RESULTS: Patients were mostly satisfied with the quality of their CDs. Only 7.2% of the patients were absolutely not satisfied with their dentures. Patients with a low level of education were more satisfied in general with their aesthetic appearance. Patients with better self-perception of their affective status and quality of life showed higher levels of general satisfaction. Patients with better self-perception of their economic status showed lower levels of satisfaction. Younger patients wearing dentures for the first time, with short periods of being edentulous, and with better quality maxillary denture-bearing areas were more satisfied with the retention of maxillary CDs. In contrast, younger patients with first-time dentures, a short period of being edentulous, and with better quality mandibular denture-bearing areas gave lower ratings to the retention and comfort of wearing mandibular dentures. CONCLUSIONS: Level of education, self-perception of affective and economic status, and quality of life are all related to patient satisfaction. However, the quality of dentures shows the strongest correlation with patient satisfaction. Not only the quality of the denture-bearing area but the denture-wearing experience itself seems to be more important in determining patient satisfaction with mandibular CDs.     

Assessment of defects and amorphous structure produced in raffinose pentahydrate upon dehydration

The progressive conversion of crystalline raffinose pentahydrate to its amorphous form by dehydration at 60 degrees C, well below its melting temperature, was monitored by X-ray powder diffraction over a period of 72 h. The presence of defects within the crystal structure and any amorphous structure created was determined computationally by a total diffraction method where both coherent long-range crystalline order and incoherent short-range disorder components were modeled as a single system. The data were analyzed using Rietveld, pair distribution function (PDF), and Debye total diffraction methods. Throughout the dehydration process, when crystalline material was observed, the average long-range crystal structure remained isostructural with the original pentahydrate material. Although the space group symmetry remained unchanged by dehydration, the c-axis of the crystal unit cell exhibited an abrupt discontinuity after approximately 2 h of drying (loss of one to two water molecules). Analysis of diffuse X-ray scattering revealed an initial rapid build up of defects during the first 0.5 h with no evidence of any amorphous material. From 1-2 h of drying out to 8 h where the crystalline structure is last observed, the diffuse scattering has both amorphous and defect contributions. After 24 h of drying, there was no evidence of any crystalline material remaining. It is concluded that the removal of the first two waters from raffinose pentahydrate created defects, likely in the form of vacancies, that provided the thermodynamic driving force and disorder for subsequent conversion to the completely amorphous state.