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Pendidikan tanpa diskriminasi merupakan tujuan bernegara dalam UUD 1945 untuk mencerdaskan kehidupan bangsa yang berakhlak mulia, menjunjung nilai agama dan kebudayaan lokal. Internalisasi nilai tersebut dilakukan Pemerintah Kota Padang melalui Instruksi Walikota Padang Nomor 451.442/Binsos-III/2005 mengenai penggunaan pakaian muslim bagi siswi di sekolah. Aturan tersebut dinilai bermasalah dari segi kewenangan membentuk hukum dan substansi yang diskriminatif karena diwajibkan kepada siswi non-Muslim. Sehingga perlu diteliti kewenangan dan pengaturan pakaian seragam sekolah terkait penerbitan aturan tersebut. Penelitian doktrinal (normatif) dilakukan dengan sinkronisasi hukum secara vertikal. Hasilnya menunjukkan Instruksi Walikota Padang telah sinkron dengan Pancasila, UUD 1945, dan peraturan perundang-undangan. Tidak terdapat pertentangan dalam kewenangan ataupun perumusan norma. Permasalahan diskriminasi terjadi dalam implementasi oleh sekolah karena menyalahartikan kata “menyesuaikan” (anjuran) menjadi “kewajiban” berpakaian muslim termasuk bagi siswi non-Muslim.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic commonly called COVID-19 brought new changes to healthcare delivery in the US. The purpose of this study is to identify the impact of COVID-19 on the delivery of acute surgical care for patients at a Level 1 trauma center during the lockdown period of the pandemic from March 13-May 1 2020. Methods: All trauma admission to the University Medical Center Level 1 Trauma Center from March 13 to May 13, 2020, were retrospectively abstracted and compared to the same period during 2019. Analysis focused on the lockdown period of March 13-May 1, 2020, and compared to the same dates in 2019. Abstracted data included demographics, care timeframes, length of stay, and mortality. The data were analyzed using Chi-Square, Fisher Exact, and the Mann-Whitney U test. Results: A total of 305 (2019) vs. 220 (2020) procedures were analyzed. No significant differences were seen in mean BMI, Injury Severity Score, American Society of Anesthesia Score, and Charlson Comorbidity Index between the two groups. Diagnosis time, interval to surgery, anesthesia time, surgical preparation time, operation time, transit time, mean hospital stay, and mortality were similar. Conclusion: The results of this study demonstrate that the lockdown period of the COVID-19 pandemic did not significantly affect the trauma surgery service line, aside from case volume, at a Level 1 trauma center in West Texas during the lockdown period. Despite changes to healthcare delivery during the pandemic, care of surgical patients was conserved as timely and of high quality.

Despite recent advancements in endovascular technology and the proven durability of open surgery, extensive thoracoabdominal aortoiliac occlusive disease (AIOD) remains challenging to treat. In the present report, we have described the case of a 58-year-old woman with AIOD and multiple medical comorbidities. She successfully underwent a novel intraoperative transesophageal echocardiography-guided combined treatment with concurrent descending thoracic aorta to bilateral femoral artery bypass and thoracic endovascular aortic repair. We have shown that this approach, which combines descending thoracic aorta to bilateral femoral artery bypass with thoracic endovascular aortic repair, is an effective treatment alternative for future cases of complex AIOD.

The Covid-19 pandemic has had a negative impact on business in various sectors and is one of the factors that causes the high number of filings for Bankruptcy cases in the Commercial Court. To prevent this, Law Number 37 of 2004 on Bankruptcy & Suspension of Debt Payment Obligation provides an opportunity for debtors to apply for suspension of debt payment as an opportunity to pay off their debts. However, in the process of determining the status of the application for suspension of debt payment obligations until the settlement plan for the suspension of debt payment obligations has been homologated, Law Number 37 of 2004 on Bankruptcy & Suspension of Debt Payment Obligation still provides room for creditors with bad faith to cause disadvantages towards the debtor. Therefore, in this paper, the author examines how the legal protection for debtors on the implementation of the suspension of debt payment's peace agreement that is affected by Covid-19. The results show that there is still inadequate legal protection for debtors against suspension of debt payment's peace agreement affected by Covid-19 due to the lack of provisions that can protect debtors in the bankruptcy law and suspension of debt payment obligations

The COVID-19 pandemic has had a significant impact on various aspects of society, including economic, health, political, and work-related domains. The pandemic has also caused an emotional effect on individuals, reflected in their opinions and comments on social media platforms, such as Twitter. This study explores the evolution of sentiment in Spanish pandemic tweets through a data analysis based on a fine-tuned BERT architecture. A total of six million tweets were collected using web scraping techniques, and pre-processing was applied to filter and clean the data. The fine-tuned BERT architecture was utilized to perform sentiment analysis, which allowed for a deep-learning approach to sentiment classification. The analysis results were graphically represented based on search criteria, such as “COVID-19” and “coronavirus”. This study reveals sentiment trends, significant concerns, relationship with announced news, public reactions, and information dissemination, among other aspects. These findings provide insight into the emotional impact of the COVID-19 pandemic on individuals and the corresponding impact on social media platforms.

A supracondylar fracture of the humerus is the most common upper extremity fracture in children with concurrent neurovascular complications. However, bypass grafting in the management of a pediatric open elbow dislocation with an arterial injury has rarely been reported in the literature. Hence, an adequate conduit for a vessel graft interposition remains questionable when a primary anastomosis is limited in an arterial reconstruction. The purpose of this study is to present a brachial artery reconstruction in a 3-year-old patient with an open supracondylar fracture of the humerus. In the clinical and surgical examination of the patient, an open wound in the left antecubital fossa presented with accompanying brachial artery injury. To repair the artery, a reverse end-to-end anastomosis was conducted using basilic vein graft from the ipsilateral arm under general anesthesia. The patient had palpable radial pulses in the postoperative clinical examination and was discharged without complications. The great saphenous vein (GSV) has proven to be the most common and the best conduit for arterial reconstruction of the upper extremity in the adult patients. However, the GSV graft is known to have the propensity for becoming aneurysmal in pediatric patients. Some studies have demonstrated the basilic vein as a suitable conduit in pediatric patients, in that it has durable patency, fewer branches, size compatibility for anastomosis, and proximity to the brachial artery. Our case confirms the safety of using this autogenous vein from within the zone of injury for arterial reconstruction, after a supracondylar humeral fracture. The management of pediatric elbow fractures accompanying vascular injuries can be technically demanding due to relatively small, delicate structures and concurrent neurovascular network. Nonetheless, a vascular injury should be treated with high level of suspicion and immediate intervention to avoid any limb ischemia or loss. In situations where the brachial artery is compromised and needs repair with a bypass, the basilic vein should be considered as a conduit for its greater accessibility and long-term patency.

Background: Domestic cattle (Bos taurus) are naturally susceptible to hypoxia-induced pulmonary arterial hypertension; consequently, the bovine calf has been used with considerable success as an animal model of the analogous human condition. Studies to date, however, have relied on instantaneous measurements of pressure and cardiac output. Here, we describe the surgical technique for placement of a fully implantable wireless biotelemetry device in a bovine calf for measurement of pulmonary arterial and left ventricular pressures, right ventricular output, and electrocardiogram. Methods: Three, 2-month old bovine calves underwent left-sided thoracotomies. A transit-time flow probe was placed around the pulmonary artery and solid-state pressure catheters inserted into the pulmonary artery and left ventricle. Biopotential leads were secured to the epicardium. The implant body was secured subcutaneously, dorso-caudal to the incision. Results: The implant and sensors were successfully placed in two of the three calves. One calf died from ventricular fibrillation following left ventricular puncture prior to pressure sensor insertion. Anatomical discrepancies meant that either 4th or 5th rib was removed. The calves recovered quickly with minimal complications that included moderate dyspnea and subcutaneous edema. Conclusions: Left thoracotomy is a viable surgical approach for wireless biotelemetry studies of bovine calf cardiovascular function. The real-time, contemporaneous collection of cardiovascular pressures and output, permits pathophysiological studies in a naturally susceptible, large animal model of pulmonary arterial hypertension.

Background: Youth-onset type 2 diabetes (Y-T2D) is associated with increased risk for coronary atherosclerotic disease, but the timing of the earliest pathological features and evidence of cardiac endothelial dysfunction have not been evaluated in this population. Endothelial function magnetic resonance imaging may detect early and direct endothelial dysfunction in the absence of classical risk factors (severe hyperglycemia, hypertension, and hyperlipidemia). Using endothelial function magnetic resonance imaging, we evaluated peripheral and coronary artery structure and endothelial function in young adults with Y-T2D diagnosed ≤5 years compared with age-matched healthy peers. We isolated and characterized plasma-derived small extracellular vesicles and evaluated their effects on inflammatory and signaling biomarkers in healthy human coronary artery endothelial cells to validate the imaging findings., Methods: Right coronary wall thickness, coronary artery flow-mediated dilation, and brachial artery flow-mediated dilation were measured at baseline and during isometric handgrip exercise using a 3.0T magnetic resonance imaging. Human coronary artery endothelial cells were treated with Y-T2D plasma-derived small extracellular vesicles. Protein expression was measured by Western blot analysis, oxidative stress was measured using the redox-sensitive probe dihydroethidium, and nitric oxide levels were measured by 4-amino-5-methylamino-2',7'-difluororescein diacetate., Results: Y-T2D (n=20) had higher hemoglobin A1c and high-sensitivity C-reactive protein, but similar total and LDL (low-density lipoprotein)-cholesterol compared with healthy peers (n=16). Y-T2D had greater coronary wall thickness (1.33±0.13 versus 1.22±0.13 mm; P =0.04) and impaired endothelial function: lower coronary artery flow-mediated dilation (-3.1±15.5 versus 15.9±17.3%; P <0.01) and brachial artery flow-mediated dilation (6.7±14.7 versus 26.4±15.2%; P =0.001). Y-T2D plasma-derived small extracellular vesicles reduced phosphorylated endothelial nitric oxide synthase expression and nitric oxide levels, increased reactive oxygen species production, and elevated ICAM (intercellular adhesion molecule)-mediated inflammatory pathways in human coronary artery endothelial cells., Conclusions: Coronary and brachial endothelial dysfunction was evident in Y-T2D who were within 5 years of diagnosis and did not have severe hyperglycemia or dyslipidemia. Plasma-derived small extracellular vesicles induced markers of endothelial dysfunction, which corroborated accelerated subclinical coronary atherosclerosis as an early feature in Y-T2D., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02830308 and NCT01399385., Competing Interests: None.

Objective: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and β-cell function after therapy in AA Y-T2D., Methods: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. β-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test., Results: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI., Conclusion: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance β-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed., (Published by Oxford University Press on behalf of the Endocrine Society 2023.)

Disclosure Summary: Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose., Background: Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes gastrointestinal (GI) side effects, which may contribute to reduced treatment adherence and efficacy. Prebiotic intake may reduce metformin's side effects by shifting microbiota composition and activity., Objective: The aims of this study were to determine the feasibility and tolerability of a prebiotic supplement to improve metformin-induced GI symptoms and explore the changes in glycemia and shifts in the microbiota diversity., Methods: In a two-phase pilot clinical trial, we compared, stool frequency and stool form every 1-2 days, and composite lower GI symptoms (weekly) at initiation of daily metformin combined with either a daily prebiotic or a placebo shake in a 1-week randomized double-blind crossover design (Phase 1), followed by a 1-month open-labeled extension (Phase 2). Plasma glycemic markers and stool samples were collected before and after each phase., Results: Six Y-T2DM (17.2 ± 1.7y (mean ± SD), 67% male, BMI (42 ± 9 kg/m 2 ), HbA1c (6.4 ± 0.6%)) completed the intervention. Stool frequency, stool composition, and GI symptom scores did not differ by group or study phase. There were no serious or severe adverse events reported, and no differences in metabolic or glycemic markers. After one week Phase 1metformin/placebo Proteobacteria , Enterobacteriaceae , and Enterobacteriales were identified as candidate biomarkers of metformin effects. Principle coordinate analyses of beta diversity suggested that the metformin/prebiotic intervention was associated with distinct shifts in the microbiome signatures at one week and one month., Conclusion: Administration of a prebiotic fiber supplement during short-term metformin therapy was well tolerated in Y-T2DM and associated with modest shifts in microbial composition. This study provides a proof-of-concept for feasibility exploring prebiotic-metformin-microbiome interactions as a basis for adjunctive metformin therapy., Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04209075., Competing Interests: HY is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Dixon, Mishra, Dietsche, Jain, Mabundo, Stagliano, Krenek, Courville, Yang, Turner, Meyers, Estrada, Yadav and Chung.)

Introduction: The transition from paediatric to adult diabetes care in youth-onset diabetes (type 1 diabetes mellitus, Y-T1DM and type 2 diabetes mellitus, Y-T2DM) is associated with worsening glycaemic control, missed clinical visits, decreased medication adherence and the emergence of cardiometabolic complications. The socio-ecological challenges that influence transitioning to adult diabetes care may be distinct between Y-T1DM and Y-T2DM. The goal of this scoping review is to map the state of the literature on transitioning care in Y-T2DM compared with Y-T1DM and to identify the main sources and types of evidence available. The objectives are : (1) to identify the factors within the socio-ecological framework (individual, relationship, community, societal) associated with transitioning to adult care in Y-T2DM compared with Y- T1DM, and (2) to identify knowledge gaps related to transitioning to adult care., Methods: The scoping review protocol and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews guidelines. A systematic search of scientific databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health, Scopus and APA PsycNet will be undertaken for articles between 1 January 1990 and 30 September 2022. Study designs will include peer-reviewed experimental and quasi-experimental published studies without language or country-specific restrictions. We will exclude articles on other diabetes subtypes and will exclude non-peer reviewed articles such as opinion papers, anecdotal reports or supplementary commentaries., Analysis: References will be collated, sorted and extracted using Covidence. Factors associated with transition from paediatric to adult diabetes care in Y-T1DM and Y-T2DM will be identified using the socio-ecological framework and results will be presented in narrative format, tables, and summary graphs., Ethics and Dissemination: Ethical approval will not be applicable for this review., Trial Registration Number: https://osf.io/k2pwc., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The purpose of this study was to examine the effect of pain severity on activity levels and physical disability in the context of high pain acceptance. We hypothesized that pain acceptance moderates the effect of pain severity on general activity and physical disability, such that at higher levels of acceptance, the deleterious effect of pain is mitigated., Methods: Two hundred seven patients with chronic pain were recruited from three clinics in a large southwestern military treatment facility. Participants completed an anonymous self-report battery of standardized measures, including the Chronic Pain Acceptance Questionnaire, modified Oswestry Disability Index, and Pain Severity and General Activity subscales of the West Haven-Yale Multidimensional Pain Inventory., Results: Chronic pain acceptance was found to significantly moderate relations between pain severity and general activity (b  =  0.0061, t(198) = 2.75, P = 0.007, 95% confidence interval [CI] = 0.002 to 0.011) and pain severity and disability (b  =  0.036, t(193) = -2.564, P = 0.011, 95% CI = -0.063 to -0.008). In the context of higher acceptance, the negative effect of pain on activity and disability appeared reduced. Conversely, in the context of low acceptance, the effect of pain on disability appeared accentuated at all levels of pain severity., Conclusions: Higher acceptance mitigated both activity level and disability in a military-affiliated clinical sample of patients with chronic pain. Results further establish the role of acceptance in relation to functioning in a unique sample of people with chronic pain. These findings have implications for understanding and enhancing functioning in chronic pain populations., (© 2018 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A new nanohybrid composite activated by sonic energy has been recently introduced as a single-step, bulk-fill restorative material. The purpose of this study was to compare the physical properties of this new composite to various other composite restorative materials marketed for posterior or bulk-fill placement. The following physical properties were examined: depth of cure, volumetric shrinkage, flexural strength, flexural modulus, fracture toughness, and percent porosity. A mean and standard deviation were determined per group. One-way ANOVA and Tukey's post hoc tests were performed per property (α = 0.05). Percent porosity was evaluated with a Kruskal-Wallis/Mann-Whitney test (α = 0.005). Significant differences were found between groups (P < 0.001) per test type. Compared to the other composite restorative materials, the new nanohybrid composite showed low shrinkage and percent porosity, moderate fracture toughness and flexural modulus, and high flexural strength. However, it also demonstrated a relatively reduced depth of cure compared to the other composites.

Background: We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%-100%) on the Karnofsky performance status (KPS) scale., Methods: Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression., Results: The sample included 984 patients: mean age was 73 years (range: 65-99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76., Conclusion: Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes., (©AlphaMed Press.)

The purpose of this randomized, double-blind clinical study was to evaluate the effectiveness of a larger-bore compared with a standard-bore dental local anesthetic needle of the same gauge in reducing pain during inferior alveolar (IA) and long buccal (LB) nerve block injections. Twenty active duty military or Department of Defense beneficiaries undergoing dental treatment were anesthetized using a split-mouth design with 4 anesthetic dental injections. Both sides of the mouth received IA nerve block and LB nerve injections, one using the 27-gauge large-bore Septoject XL needle and other using a 27-gauge standard-bore Septoject needle. Patients rated the pain experienced with each method using a visual analogue scale (VAS). The IA injection mean VAS score and standard deviation were 38.9 ± 22.7 mm and 37.1 ± 22.4 mm, respectively, for the larger and standard-bore needles. The LB injection mean VAS score and standard deviation were 33.5 ± 22.8 mm and 35.1 ± 19.6 mm, respectively, for the larger and standard-bore needles. The data were analyzed with a paired t test (α = .05). No significant difference was found between the IA (P = .70) or LB injections (P = .73). The use of a larger-bore 27-gauge needle did not reduce pain on injection compared with the standard-bore 27-gauge needle.

This study sought to determine the effect of cyclic loading and toothbrush abrasion (with and without abrasive slurries) on cervical lesion formation. The roots of extracted human third molars were embedded in acrylic resin, leaving 2 mm of root structure and crowns exposed. Teeth were divided into 6 groups (n = 10) with the following treatments: no treatment (control), cyclic load in distilled water, brushing with distilled water, cyclic load followed by brushing with distilled water, brushing with toothpaste slurry, and cyclic load followed by brushing with toothpaste slurry. Cyclic loading and toothbrushing machines subjected the teeth to 1.6 million cyclic loads and 30,000 brushing strokes, the equivalent of 4 years of function and brushing for an average patient. The teeth were scanned with a 3-dimensional optical profilometer to determine the volumetric loss of tooth structure. Load cycling had no significant effect on cervical tooth loss. Brushing with toothpaste resulted in significantly greater cervical tooth loss than brushing with water, which in turn was significantly greater than no treatment at all.

Objective: Emerging results support the value of geriatric assessment (GA) in determining the risk and benefits of cancer treatment in older adults. A brief GA tool consisting of valid and reliable measures has been developed; however, little data exist on the ability to perform the GA in community oncology clinics. The objective of this study was to determine the feasibility of performing the GA in the community., Materials and Methods: Patients aged ≥65 were eligible. The GA included a health care provider assessment of performance status, cognitive function, a Timed Up and Go test, and a self-administered patient questionnaire that evaluated measures of functional status, comorbidity, psychological state, social support, and nutritional status., Results: From 2009 to 2013, 1088 patients were assessed including 339 (31%) from seven community clinics across North Carolina. The median amount of time to complete the patient-report portion of the GA was 19min in the academic center versus 22min in the community. The median amount of time to complete the entire GA was 23min in the academic center and 30min in community settings. Significantly more patients in the community required assistance completing the questionnaire (24% vs. 14%); however, most patients required no assistance (76%)., Conclusion: A brief GA can be performed in community oncology clinics. The time to complete the professional assessments and patient self-assessments were similar in both settings. Future studies are planned to determine if such assessments can improve cancer care for older patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the resistance to wear of six commonly used orthotic appliance materials. These materials were: SR Ivocap (Ivoclar Vivadent, Inc., Amherst, NY), Eclipse (Dentsply International, York, PA), ProBase (Ivoclar Vivadent), Valplast (Valplast International Corp., Oceanside, NY), Impak (CMP Industries LLC, Albany, NY), and Clearsplint (Astron Dental Corp., Lake Zurich, IL). Twelve cylindrical specimens of each material were fabricated per manufacturer instructions. Occlusal wear was simulated in a custom-made wear simulator with each specimen receiving four wear scars in a two-body wear simulation using a 1.5 mm tungsten-carbide tipped stylus at 40 newtons for 2500 cycles at 1 Hz, while immersed in 37 degrees C distilled water (n = 48). The specimens were evaluated before and after wear testing using a three-dimensional (3D) noncontact profilometer (Proscan 2000, Scantron Corp., Eagan, MN). A mean change in volume was determined for each orthotic material. Results found that Clearsplint material displayed the greatest amount of volume loss/wear, while SR Ivocap, Eclipse, and ProBase materials had the least amount of wear. Valplast and Impak performed more moderately. Based upon this wear knowledge, practitioners are able to more reliably choose the appliance material necessary for their various patients.

This randomized, open-label study of patients in India with visceral leishmaniasis (VL) investigated the effect of food on sitamaquine and desethyl-sitamaquine pharmacokinetics. Patients were randomized to receive oral sitamaquine, 2 mg/kg/day, once a day for 21 days across four cohorts (n = 41) (fasted/fed, fed/fasted, fed/fed, and fasted/fasted) over two periods (days 1-10 and 11-21), or intravenous amphotericin B (AmB), 1 mg/kg every other day for 30 days (n = 20). Mean day 21 pharmacokinetics across the four cohorts were sitamaquine, area under curve (AUC)((0-τ)) = 6,627-8,903 ng.hr/mL, AUC((0-16)) = 4,859-6,633 ng.hr/mL, maximum plasma concentration (C(max)) = 401-570 ng/mL, apparent terminal half-life (t(1/2)) = 18.3-22.8 hr, time to reach C(max) (t(max)) = 3.5-6 hr; and desethyl-sitamaquine, AUC((0-τ)) = 2,307-3,163 ng.hr/mL, C(max) = 109-154 ng/mL, t(1/2) = 23.0-27.9 hr, t(max) = 2-10 hr, with no significant food effect. On-therapy adverse events were observed for sitamaquine in 4 (10%) of 41 patients and for AmB in 17 (85%) of 20 patients. The final clinical cure (day 180) was 85% (95% confidence interval = 70.8-94.4%) for sitamaquine and 95% (95% confidence interval = 75.1-99.9) for AmB. Sitamaquine can be taken regardless of food intake, was generally well tolerated, and showed potential efficacy in patients with visceral leishmaniasis.

The tumor suppressor, death-associated protein kinase (DAPK), is a Ca(2+)/calmodulin-regulated Ser/Thr kinase with an important role in regulating cytoskeletal dynamics. Autophosphorylation within the calmodulin-binding domain at Ser-308 inhibits DAPK catalytic activity. Dephosphorylation of Ser-308 by a previously unknown phosphatase enhances kinase activity and proteasome-mediated degradation of DAPK. In these studies, we identified two holoenzyme forms of protein phosphatase 2A (PP2A), ABalphaC and ABdeltaC, as DAPK-interacting proteins. These phosphatase holoenzymes dephosphorylate DAPK at Ser-308 in vitro and in vivo resulting in enhanced kinase activity of DAPK. The enzymatic activity of PP2A also negatively regulates DAPK levels by enhancing proteasome-mediated degradation of the kinase. Overexpression of wild type DAPK induces cell rounding and detachment in HEK293 cells; however, this effect is not observed following expression of an inactive DAPK S308E mutant. Finally, activation of DAPK by PP2A was found to be required for ceramide-induced anoikis. Together, our results provide a mechanism by which PP2A and DAPK activities control cell adhesion and anoikis.

Background: Internal and external fixation techniques have been developed to provide rigidity and stability to a fusion site such as in tibiotalocalcaneal (TTC) arthrodesis. Compression of the fusion site plays an integral role in primary bone healing, though little work has been done to quantify the compressive force values of ankle fixation devices., Materials and Methods: Using synthetic and cadaveric bone models, a Newdeal/Integra PantaNail and DePuy VersaNail were tested as compressive intramedullary (IM) nails while an Encore True/Lok and an Ace-Fischer frame were tested as external fixators., Results: The PantaNail experienced maximum compressive loads of 1898 and 1255 N in synthetic and cadaveric constructs, respectively. The VersaNail experienced max compressive loads 388 N during installation. All IM nails tested experienced decreased compressive loads after removal of the external guide and instrumentation. The external fixators were loaded to approximately 1200 N in both synthetic and cadaveric constructs. The decrease in compressive load was recorded as a function of simulated fusion site bone resorption for all devices. The IM nails experienced a 90% reduction in load with less than 1 mm of resorption, while the external fixators held 50% load for over 4 mm of resorption. These data were verified using a simple constitutive model of IM nails and external fixators., Conclusion: Intramedullary nails are capable of generating compression, however, are unable to provide sustained compression for any considerable amount of resorption. External fixators are inherently capable of applying and sustaining greater amounts of compression., Clinical Relevance: Surgeons who perform TTC arthrodesis procedures should be aware of a device's ability to generate and sustain compression with respect to bone resorption.

The development of new coronary artery constitutive models is of critical importance in the design and analysis of coronary replacement grafts. In this study, a two-parameter logarithmic complementary energy function, with normalized measured force and internal pressure as the independent variables and strains as the dependent variables, was developed for healthy porcine coronary arteries. Data was collected according to an experimental design with measured force ranging from 9.8 to 201 mN and internal pressure ranging from 0.1 to 16.1 kPa (1 to 121 mmHg). Comparisons of the estimated constitutive parameters showed statistically significant differences between the left anterior descending [LAD] and right coronary artery [RCA], but no differences between the LAD and left circumflex [LCX] or between the LCX and RCA. Point-by-point strain comparisons confirm the findings of the model parameter study and isolate the difference to the axial strain response. Average axial strains for the LAD, LCX, and RCA are 0.026 +/- 0.009, 0.015 +/- 0.005, and 0.011 +/- 0.009, respectively, at all physiologic loads, suggesting that the axial strains in the LAD are significantly higher than in the other regions.

Knowledge of blood vessel mechanical properties is fundamental to the understanding of vascular function in health and disease. Analytic results can help physicians in the clinic, both in designing and in choosing appropriate therapies. Understanding the mechanical response of blood vessels to physiologic loads is necessary before ideal therapeutic solutions can be realized. For this reason, blood vessel constitutive models are needed. This article provides a critical review of recent blood vessel constitutive models, starting with a brief overview of the structure and function of arteries and veins, followed by a discussion of experimental techniques used in the characterization of material properties. Current models are classified by type, including pseudoelastic, randomly elastic, poroelastic, and viscoelastic. Comparisons are presented between the various models and existing experimental data. Applications of blood vessel constitutive models are also briefly presented, followed by the identification of future directions in research.

To better understand the distinct functional roles of the 220- and 130-kDa forms of myosin light chain kinase (MLCK), expression and intracellular localization were determined during development and in adult mouse tissues. Northern blot, Western blot, and histochemical studies show that the 220-kDa MLCK is widely expressed during development as well as in several adult smooth muscle and nonmuscle tissues. The 130-kDa MLCK is highly expressed in all adult tissues examined and is also detectable during embryonic development. Colocalization studies examining the distribution of 130- and 220-kDa mouse MLCKs revealed that the 130-kDa MLCK colocalizes with nonmuscle myosin IIA but not with myosin IIB or F-actin. In contrast, the 220-kDa MLCK did not colocalize with either nonmuscle myosin II isoform but instead colocalizes with thick interconnected bundles of F-actin. These results suggest that in vivo, the physiological functions of the 220- and 130-kDa MLCKs are likely to be regulated by their intracellular trafficking and distribution.

Solid- and solution-phase synthesis of peptidomimetic inhibitors of urokinase-type plasminogen activator based on the sequence dSerAlaArg-al are described. The biological activities of these unique inhibitors are reported herein. Carbonate prodrugs were prepared and tested as potential drug delivery systems.

An assay for the quantification of plasma and urine levels of CVS 1123, an orally bioavailable thrombin inhibitor, and its desmethyl form. CVS 738, was developed to support clinical and toxicology studies. This assay uses solid-phase extraction, reversed-phase HPLC separation, and post-column fluorescent derivatization with ninhydrin. An internal standard is added to correct for recovery. In aqueous solution, the arginine aldehyde structures of CVS 1123 and CVS 738 exist in multiple forms which can be separated under standard reversed-phase HPLC conditions. HPLC conditions were optimized to give rapid interconversion of the forms on the separation time scale, and consequently a single chromatographic peak. Extraction conditions were modified for quantitative extraction of drug compounds from large volumes of human plasma. The assay was shown to be accurate and precise, with a quantification limit of 17 ng CVS 1123/ml human plasma.

One hundred and fifty patients with various rheumatic complaints who were taking nonsteroidal anti-inflammatory drugs (NSAIDs) and required upper gastrointestinal endoscopy were compared with 150 patients, matched for age and sex, who were also referred for gastroscopy but who did not have rheumatic complaints and were not taking these drugs. A comparison was made between the indications for endoscopy and the endoscopic findings in the two groups. Significant differences were found. Fewer patients with rheumatic complaints had normal findings, more had chronic gastric ulcer, duodenal ulcer, gastritis or mucosal erosions. Patients with rheumatic complaints were referred more frequently for anaemia and less frequently for dysphagia or abdominal symptoms. The increased severity of gastric morbidity in patients with rheumatism is probably due to damage caused by NSAIDs. The frequency and severity of upper gastrointestinal lesions in patients with rheumatic complaints taking NSAIDs cannot be estimated from the patient's complaint rate, anaemia rather than pain being the most frequent finding. Upper gastrointestinal tract endoscopy is required to make a definitive diagnosis. This has important implications for the licensing policies of regulatory authorities when considering the licensing of new nonsteroidal anti-inflammatory drugs.

Patients with arthritis who take nonsteroidal anti-inflammatory drugs (NSAIDs) often develop peptic ulceration. Withdrawal of the NSAID may lead to increased debility and thus it may be desirable to continue the NSAID while attempting to heal the ulceration by additional therapeutic measures. We have investigated the effect of cimetidine in this role. Patients with gastroscopically-proven peptic ulcer associated with NSAID ingestion were given either cimetidine or placebo treatment while continuing to take their NSAIDs. It was found that the ulceration healed in some patients over a 6-week period even on placebo treatment. There was no statistical difference found between the healing of these ulcers when compared with the cimetidine-treated group. The mechanism of NSAID-induced ulceration and the reason for the above finding is discussed.