Mechanisms and kinetics of liposome-cell interactions

Although the possibility of targeting drugs to specific tissues and cells, as well as facilitating their uptake and cytoplasmic delivery has rendered liposomes a versatile drug carrier system with numerous potential applications in medicine, the molecular mechanisms of liposome-cell interactions are not understood well. Here we have reviewed the early and current concepts of liposome-cell interactions, including possible liposome receptors. Uptake of liposomes by cells can be modified by the lipid composition, particularly by the inclusion of steric stabilizers such as PEG-conjugated lipids. Such modifications also alter the circulation time and biodistribution of liposomes, which can thus be tailored for particular applications. The intracellular fate of encapsulated molecules can be modified by the use of pH-sensitive liposomes which can also be sterically stabilized. Cationic liposomes that can undergo lipid mixing with cellular membranes can deliver complexed DNA to cells, but most likely via an endocytotic process. Kinetic analysis of liposome-cell interactions can elucidate the numbers of liposome receptors of several types and the corresponding binding constants. It is likely that liposomes bind to different cell surface receptors on different cells, and that they utilize more than one type of receptor on a particular cell. The kinetic analysis also provides the rate constants of endocytosis and the percentages of liposomes that are bound or endocytosed.     

Plastic and Reconstructive Body Contouring in the Post-vertical Banded Gastroplasty Patient: a retrospective review

Class IV obesity (body mass index > 40) is associated with an increased risk of a variety of health problems, many of them potentially life-threatening or life-shortening. Vertical banded gastroplasty (VBG) is currently the most frequently performed surgical procedure used to restrict food intake and assist with weight loss. After massive weight loss, however, redundant abdominal and breast tissue can result in physiological and psychological problems related to an unusual body habitus. Patients complain of difficulties with daily activities, choice of clothing, social acceptance, etc. Body contouring has proven to be an important part of the rehabilitation of the morbidly obese patient, and we have therefore reviewed the records of 55 patients who experienced massive weight loss following VBG and then underwent abdominoplasty with or without mammoplasty/mastopexy, in order to assess the parameters which will be seen more frequently in the future by plastic surgeons as bariatric surgery becomes more widely accepted and performed.     

Cancer Incidence in Kentucky, Pennsylvania, and West Virginia: Disparities in Appalachia

CONTEXT: Composed of all or a portion of 13 states, Appalachia is a heterogeneous, economically disadvantaged region of the eastern United States. While mortality from cancer in Appalachia has previously been reported to be elevated, rates of cancer incidence in Appalachia remain unreported. PURPOSE: To estimate Appalachian cancer incidence by stage and site and to determine if incidence was greater than that in the United States. METHODS: Using 1994--1998 data from the central registries of Kentucky, Pennsylvania, and West Virginia, age-adjusted incidence rates were calculated for the rural and nonrural regions of Appalachia. These state rates were compared to rates from the Surveillance, Epidemiology, and End Results (SEER) program for the same years by calculating the adjusted rate ratio (RR) and a 95% confidence interval (CI). FINDINGS: Both the entire and rural Appalachian regions had an adjusted incidence rate for all cancer sites similar to the SEER rate (RR = 1.00 [95% CI, 1.00-1.01] and RR = 0.99 [95% CI, 0.99-1.00], respectively). However, incidence of cancer of the lung/ bronchus, colon, rectum, and cervix in Appalachia was significantly elevated (RR = 1.22 [95% CI, 1.20-1.23], 1.13 [95% CI, 1.11-1.14], 1.19 [95% CI, 1.16-1.22], and 1.12 [95% CI, 1.07-1.17], respectively). Incidence of cancer of the lung/bronchus and cervix in rural Appalachia was even more elevated (RR = 1.34 [95% CI, 1.31-1.36] and 1.29 [95% CI, 1.21-1.38], respectively). Incidence of unstaged disease for all cancer sites in Appalachia (RR = 1.06 [95% CI, 1.05-1.08]), particularly rural Appalachia (RR = 1.28 [95%CI, 1.25-1.301), was elevated. CONCLUSIONS: Cancer incidence in Appalachia was not found to be elevated. However, incidence of cancer of the lung/bronchus, colon, rectum, and cervix was elevated in Appalachia. The rates of unstaged cancer of every examined site were elevated in rural Appalachia, suggesting a lack of access to cancer health care.     

Monkeypox DNA levels correlate with virus infectivity in clinical samples,Israel, 2022

The current monkeypox virus global spread and lack of data regarding clinical specimens’ infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.     

Systemic review of the robustness of randomized controlled trials for the treatment of cholangiocarcinoma in three domains: survival-inferred fragility index,restricted mean survival time,and the spin effect

BackgroundThe vast majority of patients with cholangiocarcinoma (CC) have advanced disease at diagnosis and are candidates for palliative treatment only. The robustness of the randomized controlled trials regarding the treatment of CC are assessed.MethodsA systematic review of all randomized control trials (RCT) of treatments for both intra- and extrahepatic CC between 2010 and 2020 was performed. The survival-inferred fragility index (SIFI; the minimum number of reassignments of the best survivors between arms that would overturn the statistical outcomes) was calculated. In addition, the gain, or loss, in survival in RCTs was evaluated by the restricted mean survival time (RMST) difference. Finally, the level of spin i.e., misrepresentation of study outcomes, was measured in inconclusive studies to assess distorted reporting strategies.ResultsOut of 6,167 studies retrieved, 11 could be retained for full text revision (7 with both intra- and extrahepatic CC, 3 with peri-hilar CC, and 1 with peri-hilar or distal CC). Only 3 studies included resected patients (2 with both intra- and extrahepatic CC and 1 with peri-hilar or distal CC). Nine studies investigated systemic chemotherapy (including 3 after surgical resection), one study evaluated photodynamic therapy, and another investigated the use of an endoscopically inserted stent in the biliary tract. The median SIFI was −2 [interquartile range (IQR): −6.25, −0.25] across all studies. Overall, the median RMST difference was 0.56 months (IQR: 0.10, 0.95). Finally, for inconclusive studies, the level of spin was high, moderate, and low in respectively 12.5%, 25%, and 62.5% of the studies.ConclusionsRCTs of CC showed a low degree of robustness with a frequent proportion of associated spin.     

Stress Coping Strategies,Burnout, Secondary Traumatic Stress,and Compassion Satisfaction Amongst Israeli Dentists: A Cross-sectional Study

ObjectiveBeing a member of the dental profession is often associated with stress and high levels of burnout. Stress coping strategies may significantly help mediate burnout. The present cross-sectional study sought to examine the role of stress coping strategies on burnout, secondary traumatic stress, and compassion satisfaction amongst Israeli dentists.MethodsThe study was carried out amongst Israeli dentists with the use of the following questionnaires: (1) the Professional Quality of Life Scale 5 (ProQOL), referring to burnout, compassion satisfaction, and level of secondary traumatic stress; (2) the Coping Inventory for Stressful Situations–Situation Specific Coping Inventory (CISS-SSC), referring to coping strategies (task-focused, emotion-focused, or avoidance-focused coping); and (3) demographic and professional variables (eg, specialisation, workload). Participants included 243 Israeli dentists. Univariate analyses and linear regressions were conducted to evaluate the relationships amongst coping strategies and burnout, secondary traumatic stress, and compassion satisfaction.ResultsFemale dentists had higher emotion-focused and avoidance coping scores than male dentists. Burnout could be explained by higher emotion-focused coping scores and lower task-focused and avoidance-focused coping. Secondary traumatic stress could be explained by higher emotion-focused scores, having fewer years of professional experience, and younger ages. Compassion satisfaction could be explained by lower emotion-focused coping as well as by higher task-focused coping and workload scores, specialisation, and gender.ConclusionsThe findings suggest that emotional coping may cause dentists to be vulnerable to burnout and to secondary traumatic stress.Key words: Dentistry, Coping strategies, Burnout, Secondary traumatic stress, Professional quality of life, Compassion satisfaction     

The Change in Retentive Values of Locator Attachments and Hader Clips over Time

Purpose: The aim of this study was to examine early changes in retentive values of implant overdenture attachments during multiple pulls.
Materials and Methods: Two implant attachment systems (Hader bar and clip, Locator system) were used in this study. The experimental groups were divided into yellow Hader clips, white Locator attachments, and green Locator attachments. Each group consisted of 21 matrix attachments. The attachments were placed into a custom-made acrylic resin block seated passively on another acrylic block containing a Hader bar or two Locator abutments with different angulations. Each attachment was subjected to 20 consecutive pulls using a universal testing machine. The peak load-to-dislodgement of the attachments after each pull was documented, and the percent reduction of the peak load-to-dislodgement was calculated. One-way ANOVA and Tukey's honestly significant difference test were used for data analyses. A p ≤ 0.05 was considered significant.
Results: There was a significant difference in the percent reduction in peak load-to-dislodgement between the attachments after the first pull ( p = 0.005) and after the final pull ( p = 0.0001). The yellow Hader clips exhibited the least percent reduction in peak load-to-dislodgement (6.50 ± 3.59%) after the first pull, followed by the white Locator attachments (8.60 ± 4.42%); the green Locator attachments exhibited the greatest reduction (11.05 ± 4.94%).
Conclusion: The results of this in vitro study demonstrate that retentive values of the Locator attachments are reduced significantly after multiple pulls. Although this reduction might not be noticeable to the patient, it is recommended that the clinician place and remove the overdenture multiple times before delivery.     

The effectiveness of protraction face mask therapy: A meta-analysis

This study examined the effectiveness of maxillary protraction with orthopedic appliances in Class III patients. A meta-analysis of relevant literature was performed to determine whether a consensus exists regarding controversial issues such as the timing of treatment and the use of adjunctive intraoral appliances. An initial search identified 440 articles relating to Class III malocclusion. Among those articles, 11 studies in English and 3 studies in foreign languages met the previously established selection criteria. Data from the selected studies were categorized by age and appliance groups for the meta-analysis. The sample sizes were comparable between the groups. The statistical synthesis of changes before and after treatment in selected cephalometric landmarks showed no distinct difference between the palatal expansion group and nonexpansion group except for 1 variable, upper incisor angulation, which increased to a greater degree in the nonexpansion group. This finding implies that more skeletal effect and less dental change are produced in the expansion appliance group. Examination of the effects of age revealed greater treatment changes in the younger group. Results indicate that protraction face mask therapy is effective in patients who are growing, but to a lesser degree in patients who are older than 10 years of age, and that protraction in combination with an initial period of expansion may provide more significant skeletal effects. Overall mean values and corresponding standard deviations for the studies selected can also be used to estimate mean treatment effects expected from the use of protraction face mask.