Tailored synthesis of pH-responsive biodegradable microcapsules incorporating gelatin, alginate, and hyaluronic acid for effective-controlled release.

In response to escalating environmental concerns and the urgent need for sustainable drug delivery systems, this study introduces biodegradable pH-responsive microcapsules synthesized from a blend of gelatin, alginate, and hyaluronic acid. Employing the coacervation process, capsules were created with a spherical shape, multicore structure, and small sizes ranging from 10 to 20 µm, which exhibit outstanding vitamin E encapsulation efficiency. With substantial incorporation of hyaluronic acid, a pH-responsive component, the resulting microcapsules displayed noteworthy swelling behavior, facilitating proficient core ingredient release at pH 5.5 and 7.4. Notably, these capsules can effectively deliver active substances to the dermal layer under specific skin conditions, revealing promising applications in topical medications and cosmetics. Furthermore, the readily biodegradable nature of the designed capsules was demonstrated through Biochemical Oxygen Demand (BOD) testing, with over 80 % of microcapsules being degraded by microorganisms after one week of incubation. This research contributes to the development of responsive microcapsules and aligns with broader environmental initiatives, offering a promising pathway to mitigate the impact of microplastics while advancing various applications.

The Impact of Item Model Parameter Variations on Person Parameter Estimation in Computerized Adaptive Testing With Automatically Generated Items.

Sibling items developed through automatic item generation share similar but not identical psychometric properties. However, considering sibling item variations may bring huge computation difficulties and little improvement on scoring. Assuming identical characteristics among siblings, this study explores the impact of item model parameter variations (i.e., within-family variation between siblings) on person parameter estimation in linear tests and Computerized Adaptive Testing (CAT). Specifically, we explore (1) what if small/medium/large within-family variance is ignored, (2) if the effect of larger within-model variance can be compensated by greater test length, (3) if the item model pool properties affect the impact of within-family variance on scoring, and (4) if the issues in (1) and (2) are different in linear vs. adaptive testing. Related sibling model is used for data generation and identical sibling model is assumed for scoring. Manipulated factors include test length, the size of within-model variation, and item model pool characteristics. Results show that as within-family variance increases, the standard error of scores remains at similar levels. For correlations between true and estimated score and RMSE, the effect of the larger within-model variance was compensated by test length. For bias, scores are biased towards the center, and bias was not compensated by test length. Despite the within-family variation is random in current simulations, to yield less biased ability estimates, the item model pool should provide balanced opportunities such that "fake-easy" and "fake-difficult" item instances cancel their effects. The results of CAT are similar to that of linear tests, except for higher efficiency.

Comparison of Risk of Pneumonia Caused by Fluticasone Propionate versus Budesonide in Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

INTRODUCTION: Inhaled corticosteroids (ICSs) play an important role in lowering the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD). However, ICSs are known to increase the risk of pneumonia. Moreover, previous studies have shown that the incidence rate of pneumonia varies depending on the type of ICS. In this study, the risk of pneumonia according to the type of ICS was investigated in a population-based cohort. METHODS: A retrospective cohort study was conducted using claims data of the entire population from the Korean National Health Insurance Service. Patients who were newly diagnosed with COPD and prescribed fluticasone propionate or budesonide were enrolled as study subjects. Cumulative doses of ICSs were classified into categorical variables to analyze the risk of pneumonia within identical ICS doses. RESULTS: A total of 47,473 subjects were identified and allocated as 14,518 fluticasone propionate and 14,518 budesonide users through 1:1 propensity score matching. Fluticasone propionate users were more likely to develop pneumonia than budesonide users (14.22% vs 10.66%, p<0.0001). The incidence rate per 100,000 person-years was 2,914.77 for fluticasone propionate users and 2,102.90 for budesonide users. The hazard ratio (HR) of pneumonia in fluticasone propionate compared to budesonide was 1.34 (95% CI 1.26-1.43, p<0.0001). The risk of pneumonia for fluticasone propionate compared to budesonide increased with higher ICS cumulative doses: 1.06 (0.93-1.21), 1.41 (1.19-1.66), 1.41 (1.23-1.63), and 1.49 (1.33-1.66) from the lowest to highest quartiles, respectively. CONCLUSION: ICS types and doses need to be carefully considered during treatment with ICSs in patients with COPD.

Predictors of USMLE Step 1 Outcomes: Charting Successful Study Habits.

BACKGROUND: The United States Medical Licensing Examination Step 1 is a test that affects many aspects of medical students' careers. The aim of this study was to assess the predictive value of various studying habits and academic traits. ACTIVITY: A survey concerning Step 1 study habits and scores was collected and analyzed. RESULTS AND DISCUSSION: Study results showed that preclinical curriculum grades, practice test scores, and the number of practice questions completed were positively correlated with Step 1 scores. The strongest predictor of Step 1 scores was preclinical curriculum grades: each unit increase in a letter grade was associated with a 12-point increase in Step 1 scores.

High flow nasal cannulae oxygen therapy in acute-moderate hypercapnic respiratory failure.

INTRODUCTION: Severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a significant event that results in substantial mortality. OBJECTIVES: We evaluated the effectiveness of the high flow nasal cannulae (HFNC) therapy in severe AECOPD with moderate hypercapnic acute respiratory failure (ARF) compared to non-invasive ventilation (NIV). METHODS: The prospective observational trial was performed to compare the effectiveness between the HFNC and NIV in severe AECOPD with moderate hypercapnic ARF. The end point was the intubation rate and 30-day mortality. RESULTS: Ninety-two AECOPD patients enrolled during study periods. The median age was 73 (66.5-79) years, and 57 patients (64.8%) were male. Forty-four patients were assigned to HFNC, and 44 patients were assigned to NIV. The intubation rate at day 30 was 25.0% in the HFNC group and 27.3% in the NIV group (P = .857), and the 30-day mortality was 15.9% in the HFNC group and 18.2% in the NIV group (P = .845). The pH (7.38 ± 0.59 vs 7.36 ± 0.10, P = .295), PaO2 (82.2 ± 24.9 vs 81.6 ± 21.7 mm Hg, P = .899) and PaCO2 (46.8 ± 15.2 vs 51.7 ± 17.2 mm Hg, P = .160) after 6 hours and the pH (7.39 ± 0.07 vs 7.39 ± 0.08, P = .743), PaO2 (84.3 ± 18.5 vs 84.7 ± 23.2 mm Hg, P = .934) and PaCO2 (47.0 ± 16.0 vs 49.6 ± 13.7 mm Hg, P = .422) after 24 hours were not significantly different. CONCLUSION: There was no difference of the 30-day mortality and intubation rate between HFNC and NIV groups.

Latino Sexual Beliefs Scale: An Exploratory Factor Analysis of Latino Men Who Have Sex With Men.

The catalyzing forces behind risky sexual behavior are a rich area of interest for public health researchers concerned with reducing HIV risk. Social cognitive theory would suggest that sexual beliefs are a viable example of one such influential agent. Recognizing that culture plays an important role in forming such sexual beliefs, and seeking to understand the unique HIV risks present for Latino men who have sex with men (MSM), this article presents an exploratory factor analysis of the 13-item Latino Sexual Beliefs Scale (LSBS) created as part of a larger study to investigate predictors of condom use among a sample of 482 MSM born in Brazil, Colombia, and the Dominican Republic and living in the U.S. The current analysis identified two psychometric factors in the LSBS as Romantic Exigency (containing six items with a mean loading of .62) and Sexual Acquiescence (containing seven items with a mean loading of .57). This is the first factor analysis conducted on the 13-item LSBS and represents the first known quantitative measure of Latino cultural sexual beliefs related to condom use for Latino MSM. Implications for future research include further validation, use in studies exploring the role of sexual beliefs on condom use, and possible thematic targets in HIV risk reduction interventions.

Posttraumatic growth among combat veterans: A proposed developmental pathway.

With the large number of combat veterans returning from war, there is an ever-increasing need to understand ways to help soldiers and veterans successfully navigate their return to life after combat. Posttraumatic growth (PTG) offers strong protective elements following combat, including reduction in suicidal ideation (Bush et al., 2011). The purpose of this study was to explore a proposed psychosocial developmental pathway between posttraumatic stress symptoms and PTG among combat veterans of the Afghanistan and Iraq wars. The indirect pathway from posttraumatic symptoms to PTG through negative psychosocial development was found to be significant and positive. It appears that psychosocial development may indeed mediate the process by which combat veterans can make meaning from their experiences, improving overall well-being.

Estimation of the latent mediated effect with ordinal data using the limited-information and Bayesian full-information approaches.

It is common to encounter latent variables with ordinal data in social or behavioral research. Although a mediated effect of latent variables (latent mediated effect, or LME) with ordinal data may appear to be a straightforward combination of LME with continuous data and latent variables with ordinal data, the methodological challenges to combine the two are not trivial. This research covers model structures as complex as LME and formulates both point and interval estimates of LME for ordinal data using the Bayesian full-information approach. We also combine weighted least squares (WLS) estimation with the bias-corrected bootstrapping (BCB; Efron Journal of the American Statistical Association, 82, 171-185, 1987) method or the traditional delta method as the limited-information approach. We evaluated the viability of these different approaches across various conditions through simulation studies, and provide an empirical example to illustrate the approaches. We found that the Bayesian approach with reasonably informative priors is preferred when both point and interval estimates are of interest and the sample size is 200 or above.

The insecure psychotherapy base: Using client and therapist attachment styles to understand the early alliance.

The purpose of this study was to test the notion that complementary attachments are best for achieving a secure base in psychotherapy. Specifically, we predicted third to fifth session alliance from client- and therapist-rated attachment style interactions. Using a combined sample of 46 therapy dyads from a community mental health clinic and university counseling center, the client- and therapist-perceived therapy alliance, attachment anxiety, and attachment avoidance were examined at the beginning of therapy. The results of an Actor-Partner Interdependence Model (APIM; Kenny & Cook, 1999, Partner effects in relationship research: Conceptual issues, analytic difficulties, and illustrations. Personal Relationships, 6, 433-448.) indicated that there was no direct effect of either client or therapist attachment style on therapist or client early ratings of the alliance. One significant interaction emerged and indicated that client-perceived alliance was influenced by therapist and client attachment anxiety. The client-perceived early alliance was higher when more anxious therapists worked with clients with decreasing anxiety. The client early alliance was higher when less anxious therapists worked with clients with increasing anxiety. The findings partially support the notion that different attachment configurations between the therapist and client facilitate greater alliance, but this was the case only when assessing client-perceived early alliance and only with regards to the dimension of attachment anxiety. There were no significant main effects or interactions when exploring therapist-perceived alliance. Implications of the findings are discussed along with recommendations for future study and clinical training.

Adult attachment, attachment to the supervisor, and the supervisory alliance: how they relate to novice therapists' perceived counseling self-efficacy.

The supervisory relationship is one of the most important components in training therapists' professional development, and it is a frequent area of training-focused research. The current study explored how 57 training therapists' adult romantic attachments relate to the attachment to the supervisor and the supervisory working alliance. Additionally, we explored how both adult attachment and supervisory attachment relate to trainees' perceptions of their counseling self-efficacy (CSE). Results revealed that therapists with higher levels of fearful attachment to the supervisors and avoidant attachment in adult romantic relationships had less perceived CSE. Hierarchical regression revealed that it was the avoidant adult romantic attachment and the supervisory working alliance that accounted for the most significant variance in CSE, not the attachment to the supervisor. Path analysis using structural equation modeling was used to explore both the direct and indirect paths to CSE. When all variables were explored together, only the path from romantic attachment avoidance to fearful attachment to the supervisor was significant. Adult romantic attachment no longer directly related to CSE when including all the variables in the model. Implications of the findings will be discussed with regard to future research that is needed, the use of attachment-based supervisory interventions, and the application of the findings in clinical training.

New therapeutic approaches to combat arterial thrombosis: better drugs for old targets, novel targets, and future prospects.

Cardiovascular disease and stroke are predominant causes of death in developed countries. Rupture of atherosclerotic plaque in an artery wall and the ensuing thrombotic events are the triggers for acute ischemic injury in these diseases. Platelet activation and aggregation play key roles in this process of atherothrombosis. Anti-platelet drugs thus provide the primary therapeutic strategy to combat these diseases. Dual therapy with aspirin and clopidogrel is the current standard of care for most patients, but it has significant limitations. This provides an impetus for developing new anti-platelet drugs. One new drug has received FDA approval recently; prasugrel targets the platelet P2Y(12) receptor, just like clopidogrel. Several other new drugs are showing great promise in clinical trials and appear to be nearing approval. Some of these drugs have traditional targets on the platelets; others, such as vorapaxar, terutroban, and sarpogrelate, generate more excitement as they are directed against novel targets.

A Note on Confidence Intervals for Two-Group Latent Mean Effect Size Measures.

This note suggests delta method implementations for deriving confidence intervals for a latent mean effect size measure for the case of 2 independent populations. A hypothetical kindergarten reading example using these implementations is provided, as is supporting LISREL syntax.

Phototoxicity of phenylenediamine hair dye chemicals in Salmonella typhimurium TA102 and human skin keratinocytes.

Phenylenediamines (PD) are dye precursors used to manufacture hair dyes. The three PDs, 1,2-,1,3-, and 1,4-PD and three chlorinated PDs, 4-chloro-1,2-PD, 4-chloro-1,3-PD, and 4,5-dichloro-1,2-PD were studied for their mutagenic effect in Salmonella typhimurium TA 102, cytotoxicity in human skin keratinocyte cells, and for DNA cleavage. The results show that all six compounds are not toxic/mutagenic in TA 102 bacteria or skin cells, and do not cause DNA cleavage in PhiX 174 phage DNA. If the same tests are carried out by exposing them to light irradiation concurrently, all three chlorinated PDs cause mutation in TA 102 bacteria and single strand cleavage in PhiX174 phage DNA. This indicates that chlorination of the PDs makes these compounds more photochemically active and produces reactive species that cause DNA damage and mutation. For the photocytotoxicity test in skin cells, it appears there is no such structure-activity relationship. Two chlorinated PDs and two non-chlorinated PDs are cytotoxic at a fairly high concentration (1000microM) upon exposure to light irradiation.

Antibiotic prophylaxis in an animal model of chronic peritoneal exposure.

OBJECTIVES: Acute infection in an animal model of chronic peritoneal dialysis (PD) induces structural changes in the peritoneum and altersfunctional characteristics of transport. These changes may compromise observations of the chronic effects of dialysis solutions. To test the hypothesis that antibiotics would prevent acute infection without affecting transport and structural properties, we characterized the frequency of infection in our rat model of PD and examined whether the inclusion of antibiotics in the dialysis solution altered the transport and structural properties of the peritoneum. DESIGN: Female Sprague-Dawley rats were aseptically injected daily under gas anesthesia with 30 - 40 mL of a sterile solution for 2 months via a peritoneal catheter tunneled to a subcutaneous port. Solutions used were Krebs-Ringer bicarbonate (KRB) alone, KRB with antibiotics (cefazolin 200 mg/L and gentamicin 2 mg/L), KRB with 4% glucose, and KRB with both glucose and antibiotics. After 2 months, osmotic filtration andsolute transport were assessed in each animal and peritoneal fluid was collected for bacterial culture. Angiogenesis was evaluated by quantitative image analysis of tissue sections stained with CD31. Tissue content of collagen, hyaluronic acid, and sulfated glycosaminoglycan was determined. RESULTS: Technique survival (successful PD for 2 months) and infection rate were comparable among all treated groups. There were no differences between the groups in transport properties. Structural changes were comparable between groups, with or without antibiotics. CONCLUSIONS: Addition of antibiotics to the dialysis solution did not affect thetransport characteristics of the peritoneum or the pathologic reaction of the tissue to the PD solution.

Intraperitoneal immunotherapy for metastatic ovarian carcinoma: Resistance of intratumoral collagen to antibody penetration.

PURPOSE: Convective transport of macromolecules from the peritoneal cavity into tumor is determined by its hydraulic permeability and the pressure gradient. Previous studies showed that establishing a pressure gradient into the tumor failed to result in significant penetration. This study addresses the hypothesis that the extracellular matrix is the major resistance to the penetration of an i.p. injected antibody. EXPERIMENTAL DESIGN: Human ovarian tumors (SKOV-3 and OVCAR-3) were established in the abdominal wall of athymic rats. After anesthesia, the tumor serosal surface was treated for 2 hours with Krebs solution (control), collagenase (37.5 unit/mL), or hyaluronidase (10 unit/mL) followed by 3 hours of convective delivery of radiolabeled IgG. Transport of antibody into the tumor was measured with quantitative autoradiography along with the tumor interstitial pressure, concentration of collagen and hyaluronic acid, and IgG volume of distribution. RESULTS: Antibody was excluded from 42% to 53% of tumor extracellular volume. Exposure of tumors to hyaluronidase did not enhance IgG transport despite removal of 90% of the hyaluronan from the exposed tumor. In contrast, collagenase reduced collagen content, lowered tumor interstitial pressure, and markedly enhanced antibody penetration. CONCLUSIONS: Reduction of collagen, but not hyaluronan, in the matrix of ovarian xenografts enhanced the transport of i.p. injected antibody. Although high interstitial pressure is a deterrent to convective transport of macromolecules into the tumor parenchyma, the structure of the interstitial matrix provides an inherent resistance, which must be overcome before effective delivery of an antibody.

Correlating structure with solute and water transport in a chronic model of peritoneal inflammation.

To study the process of chronic peritoneal inflammation from sterile solutions, we established an animal model to link structural changes with solute and water transport. Filtered solutions containing 4% N-acetylglucosamine (NAG) or 4% glucose (G) were injected intraperitoneally daily in 200- to 300-g rats and compared with controls (C). After 2 mo, each animal underwent transport studies using a chamber affixed to the parietal peritoneum to determine small-solute and protein mass transfer, osmotic filtration, and hydraulic flow. After euthanasia, parietal tissues were sampled for histological analysis, which demonstrated significant differences in peritoneal thickness (microm; C, 42.6 +/- 7.5; G, 80.4 +/- 22.3; NAG, 450 +/- 104; P < 0.05). Staining for VEGF correlated with CD-31 vessel counts (no./mm2: C, 53.1 +/- 16.1; G, 166 +/- 32; NAG, 183 +/- 32; P < 0.05). Tissue analysis showed treatment effects on tissue hyaluronan (micro/g: C, 962 +/- 73; G, 1,169 +/- 69; NAG, 1,428 +/- 69; P < 0.05) and collagen (microg/g: C, 56.9 +/- 12.0; G, 107 +/- 12; NAG, 97.6 +/- 11.4; P < 0.05) but not sulfated glycosaminoglycan. Transport experiments revealed no significant differences in mannitol transfer or osmotic flow. Changes were seen in hydrostatic pressure-driven flux (microl x min(-1) x cm(-2): C, 0.676 +/- 0.133; G, 0.317 +/- 0.124; NAG, 0.284 +/- 0.117; P < 0.05) and albumin transfer (microl x min(-1) x cm(-2): C, 0.331 +/- 0.028; G, 0.286 +/- 0.026; NAG, 0.229 +/- 0.025; P < 0.04). We conclude that alteration of the interstitial matrix correlates with diminished hydraulic conductivity and macromolecular transport.

Physiological characterization of human ovarian cancer cells in a rat model of intraperitoneal antineoplastic therapy.

Destruction of cancer cells by therapies directed against new molecular targets requires their effective delivery to the tumor. To study diffusion and convection of intraperitoneal (ip) therapy to ip tumors, we established a new athymic rat (RNU) model with ovarian tumor cells (SKOV3 and OVCAR3) implanted in the abdominal wall. The model simulates metastatic tumor and facilitates the measurement of physiological parameters that govern transport forces. CD31 immunohistochemistry revealed unique patterns of angiogenesis, with a tissue-averaged vascular volume of approximately 0.01 ml/g for each tumor. The extracellular volume (SKOV3: 0.54 +/- 0.11 ml/g, n=5; OVCAR3: 0.61 +/- 0.03, n=5) was over twice that of the adjacent normal muscle (0.22 +/- 0.06 ml/g, n=5). Intravenous-injected antibody tumor clearance was two to three times that of muscle. Interstitial pressures were higher than normal tissue with a median of 10-15 mmHg. Quantitative autoradiography of frozen tissue slices from rats exposed to ip solutions containing [14C]mannitol or 125I-immunoglobulin G (trastuzumab) was performed to determine transport of small and large molecules. With ip pressure of 0-6 mmHg, both mannitol and immunoglobulin G displayed steep concentration profiles close to the tumor surface with limited penetration deeper within the tumor tissue; antibody penetration was significantly affected by ip pressure. These results demonstrated effects of molecular size, ip pressure, the limited but highly permeable tumor vasculature, and the expanded interstitium on drug penetration from the peritoneal cavity. In conclusion, we have characterized physical and chemical parameters that determine transport of therapeutic agents in our unique tumor-bearing rat model.

ATP stimulates the release of prostacyclin from perfused veins isolated from the hamster hindlimb.

ATP-stimulated prostacyclin release from veins was investigated using epigastric veins isolated from hamsters. Veins were perfused with MOPS-buffered physiological salt solution (PSS). ATP was administered into the perfusate, and the bath solution (MOPS-PSS) was collected and assayed for the presence of the stable prostacyclin metabolite 6-keto-PGF1alpha. ATP (100 microM) resulted in reproducible increases in bath concentration from 73 +/- 22 to 279 +/- 50 pg/ml (P < 0.05, n = 5). This response was abolished by indomethacin (10 microM, P < 0.05). To ascertain whether the endothelium was the source of prostacyclin, endothelium was disrupted using air (n = 10) or deoxycholic acid (n = 6). Perfusion with air significantly reduced (P < 0.05) but did not completely abolish ATP-stimulated release of prostacyclin, while deoxycholic acid totally abolished the response (P < 0.05). The nonselective P2 receptor antagonist reactive blue 2 (100 microM) attenuated ATP-mediated release of prostacyclin but did not significantly alter ACh-stimulated release of prostacyclin. The nonselective adenosine receptor antagonist xanthine amine congener (1 microM) had no effect on ATP-stimulated release, and adenosine did not stimulate the release of prostacyclin. These results show that increases in intraluminal concentration of ATP stimulate abluminal release of prostacyclin from the venous endothelium. This effect is mediated by P2 receptors while adenosine and its receptors are not involved in this response.

Blood flow control during exercise: role for the venular endothelium?

During an increasing metabolic demand, as in exercise, the close venular-arteriolar pairing allows for diffusion of vasoactive substances from the venular blood to the arterioles. Adenosine triphosphate release from red blood cells may stimulate the venular endothelium to release vasoactive metabolites of arachidonic acid. The venous circulation is in an optimal position to provide a feedback regulation of arteriolar diameter.

Calcium-dependent synthesis of prostacyclin in ATP-stimulated venous endothelial cells.

Prostacyclin is a powerful vasodilator that is released from vascular endothelial cells. Previous studies in our laboratory have indicated that arachidonic acid metabolites from venous endothelium play an important role in the dilation of adjacent arterioles during muscle stimulation. Furthermore, recent studies have suggested that ATP released from red blood cells during hypoxia stimulates dilation of arterioles. We tested the hypothesis that an ATP-induced increase in intracellular Ca(2+) in venous endothelium promotes prostacyclin synthesis. Small branches of femoral veins were isolated from male golden hamsters, placed in a 1 mL bath, and cannulated for perfusion with 3-(N-morpholino) propanesulfonic acid (MOPS)-buffered physiological salt solution at 37 degrees C. Prostacyclin synthesis was determined by enzyme immunoassay of bath solution. Perfusion of veins with ATP increased prostacyclin synthesis from 50 +/- 5 to 627 +/- 46 pg/mL (n=49). ATP-induced prostacyclin synthesis was inhibited by removal of extracellular Ca(2+), chelation of intracellular Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) (10 micromol/L for 10 minutes), and preincubation with cytosolic phospholipase A(2) (PLA(2)) inhibitors, AACOCF(3), and bromoenol lactone. Changes in intracellular Ca(2+) in cultured human venous endothelial cells were assessed by fura-2 spectrofluorometry. ATP induced a transient Ca(2+) peak within seconds, and the subsequent Ca(2+) plateau was abolished by removal of extracellular Ca(2+). An increase in prostacyclin synthesis was detected in these cells 2 minutes after application of ATP. These findings suggest that the ATP-induced increase in intracellular Ca(2+) stimulates prostacyclin synthesis in venous endothelial cells.