Investigation of sooting flames by color-ratio pyrometry with a consumer-grade DSLR camera.
The accurate measurement of temperature in sooty flames remains a challenging task. In this study, the procedure for calibration and use of a consumer-grade digital single-lens reflex (DSLR) camera for the measurement of temperature in sooty flames using color-ratio pyrometry (CRP) is elucidated. Owing to the necessity of acquiring RAW images for CRP, investigations conducted thus far have been limited to stable flames. In this work, the potential of a CANON EOS 550D DSLR camera for measuring temperature during a transient process such as a droplet combustion event at frame rates up to 50 fps is demonstrated. The spectral response curves of the camera-lens system were obtained with the help of a tunable laser source and a laser power meter, which were subsequently used to generate lookup tables for blackbody as well as soot radiation. Soot radiation was assumed to vary with wavelength (λ) as λ-α, where α is the soot dispersion exponent. The blackbody lookup table was validated against blackbody calibration data from 1023 to 1773 K. Experiments were conducted on a candle flame as well as a McKenna flat flame burner with ethylene-air mixtures of equivalence ratios 2.1 and 2.3. For estimating temperatures using CRP, soot particles were classified as nascent and mature soot with soot dispersion exponent (α) values of 4 and 1.38, respectively. The CRP results were found to yield a decent match with thermocouple measurements as well as data reported in the literature.


Myoglobinemia and endurance exercise: a study of twenty-five participants in a triathlon competition.
Twenty-five athletes competing in a triathlon, an endurance competition, were studied to determine the relationship of sustained muscle exertion with myoglobinemia and clinical rhabdomyolysis. Of 24 athletes who completed the event, each individual demonstrated a dramatic rise and fall in serum myoglobin over a 24 hour period, with an average peak level of 842 ng/ml. While all subjects exhibited symptoms of myalgia after exertion, none required hospitalization. A significant correlation was demonstrated with average serum myoglobin and finishing time (P less than 0.0125) and postexercise temperature (P less than 0.05). Appropriate training of individuals, whether athletes or military recruits, appears to be an important factor in reducing myoglobinemia. Exercise-induced myoglobinemia appears to be dependent on intensity of athletic performance, measured as a function of time, distance, and activity performed. The athletes who finished first had the highest levels of myoglobinemia.


Propionibacterium acnes: an under-appreciated cause of post-neurosurgical infection.
Propionibacterium acnes is increasingly recognized as a cause of post-neurosurgical infection. This review of patients with P. acnes neurosurgical infection was carried out in order to determine clinical characteristics and outcomes in relation to duration of antimicrobial treatment. We retrospectively reviewed the charts of consecutive patients with P. acnes isolated from neurosurgical specimens from 1 January 1999 to 30 June 2005. We defined P. acnes neurosurgical infection as isolation of P. acnes alone from a sterile neurosurgical site in a patient who clinically improved following treatment with an appropriate antibiotic. We identified 28 patients with definite P. acnes neurosurgical infection; median age 49 years (range 23-77); 15 (54%) male. All patients had prior neurosurgical procedures: 27 (96%) post-craniotomy. The median time from surgery to presentation was 54 days (range 12-1,578). Eighteen out of 28 (64%) patients who met the definition of neurosurgical infection had Gram-positive bacilli seen in at least one surgical specimen compared with only 2/56 (4%) patients who did not meet the definition (P < 0.0001). Intravenous benzyl penicillin +/- oral penicillin VK was the most common treatment. The median duration of antibiotic treatment for intracranial infection was 29 days. Five of nine patients who had extracranial bone-flap-associated infection had <or=7 days of intravenous treatment and were cured. Two patients had relapse or reinfection. P. acnes neurosurgical infection often presents in an indolent fashion. Gram-positive bacilli on Gram stain should not be discounted as a contaminant in neurosurgical specimens. Associated bone flaps should be removed. Intravenous benzyl penicillin +/- oral penicillin VK remains effective treatment.


School-based cognitive behavioural intervention programme for addressing anxiety in 10- to 11-year-olds using short classroom activities in Japan: a quasi-experimental study.
Although several school-based cognitive behavioural intervention programmes have been developed in Japan to prevent and improve children's anxiety disorders, the substantial time required for their completion remains a problem. A brief version of the cognitive behavioural programme called 'Journey of the Brave', developed for Japanese children was conducted among 90 children aged 10‒11 years using 20-min short classroom activities, and its effectiveness was examined. The children were divided into two groups: the intervention (n = 31) and control groups (n = 59). The control group did not attend any programme sessions and followed regular school curriculum. We conducted 14 weekly programme sessions and assessed children at pre-intervention, post-intervention, and 2-month follow-up (6 months after the beginning). The primary and secondary outcome measures were the Spence Children's Anxiety Scale (SCAS) to assess children's anxiety symptoms and the Strengths and Difficulties Questionnaire (SDQ) to measure behaviour problems, respectively. A statistically significant reduction in the SCAS score in the intervention group was found at 2-month follow-up compared with the control group. A significant reduction was also observed in the SDQ score. Our findings suggested that the 'Journey of the Brave' programme, which requires only 5 h of short classroom activities, demonstrates promising results compared with previous programmes. A larger randomised control trial would be desirable. UMIN, UMIN000009021, Registered 10 March 2012.


Therapeutic potential of human embryonic stem cell transplantation in patients with cerebral palsy.
The present study evaluated the efficacy and safety of human embryonic stem cell (hESC) therapy in patients with CP. This analysis included patients (30 days-18 yr) with documented diagnosis of CP. The study consisted of four treatment phases (T1, T2, T3, T4) separated by gap phases. Efficacy of hESC therapy was evaluated based on Gross Motor Function Classification Scores Expanded and Revised (GMFCS-E & R; 1-good to 5-bad). Ninety one patients were included and all received hESC therapy in T1, 66 patients returned for T2, 38 patients for T3, and 15 patients for T4. Overall, 30.2% patients achieved GMFCS-E & R score 1 during the study with different number of patients achieving GMFCS score 1 by the end of each treatment phase (T1: 6 [6.6%]; T2: 7 [10.6%]; T3: 11 [28.9%]; and T4: 5 [33.3%]). All patients in up to 2 yr (n = 10), 2-4 yr (n = 10), 4-6 yr (n = 9), and 6-12 yr (n = 8) age groups except one of the 5 patients in the age group of 12-18 yr transitioned from GMFCS-E & R score 5 to lower scores by end of T1. Most patients transitioned to GMFCS-E & R score 2 (n = 34) from higher scores by end of T2. Eleven patients achieved GMFCS-E & R score 1 by end of T3. No serious adverse events were observed. Use of hESC therapy in patients with CP is effective and safe. hESC therapy has demonstrated significant improvement in GMFCS-E & R scale.


Conservative treatment for late-diagnosed spinal accessory nerve injury.
Spinal accessory nerve (SAN) injuries cause considerable shoulder joint dysfunction and pain, but are often underdiagnosed or diagnosed late. The aim of this study was to present the clinical and electrophysiological features and response to conservative treatment of the patients with late-diagnosed SAN injury. Nine patients diagnosed with SAN injury based on clinical and electrophysiological examinations were evaluated. All patients were treated with a standard physical therapy and rehabilitation program and then received home exercise program. Shoulder pain during rest and activity and pain causing sleep disturbances were evaluated using a visual analog scale. Constant scale investigated shoulder function. Shoulder disability questionnaire evaluated daily living activities. Results were assessed before treatment, after one month of treatment, and years after treatment. According to the electrophysiological studies, seven patients had partial and two patients had total axonal SAN injuries. The delay from the time of injury to diagnosis ranged between 12 and 84 mo (median 14 mo). When compared with the baseline values, visual analog scale, Constant scale, and shoulder disability questionnaire scores were significantly improved in all of the patients. For patients with late-diagnosed SAN injury, conservative treatment seems to be an effective treatment option.


Associations Between Early Implant Failure, Patient Age, and Patient Mortality: A 15-Year Follow-Up Study on 2,566 Patients Treated with Implant-Supported Prostheses in the Edentulous Jaw.
The aim of this study was to report the distribution of patients with early implant failures after implant treatment in the edentulous jaw with regard to age at surgery and association with patient mortality over a 15-year period. All consecutively treated patients treated in the edentulous jaw at a single specialist clinic from 1986 to 1997 were included and followed up for 1 year for implant failures and for 15 years with regard to patient mortality. Patients were arranged into age groups, and life tables for patients and reference groups of patients with comparable age (based on national population data) were calculated. Log rank test was used to test differences in patient survival between those with reported early implant failures and those with no early failures. Mantel-Haenszel chi-square test was used to test association between proportions of implant failures and age groups. A total of 55 patients were excluded because they were not living in Sweden (nonresidents/emigrated). Altogether, 2,566 patients were included, with a mean age of 65 years (SD: 11). Of these, 988 patients were deceased during the 15 years of follow-up (38%), and 291 presented an early implant failure (11.3%), most of them before prosthesis placement (72%). Patients with early implant failures presented higher mortality rates than patients with no failures (P < .05), and failure rates decreased consistently from younger to higher age groups (P < .05). Patients in the younger age groups showed an increased mortality compared with the reference group (P < .05) and a higher prevalence of early failures compared with older patients (P < .05). Older patients showed an opposing pattern of lower mortality compared with reference groups of comparable age (P < .05), but both younger and older patients with early failures showed a higher mortality compared to patients with no failures (P < .05).


Diverse HCV Strains And HIV URFS Identified Amongst People Who Inject Drugs In India.
Although the prevalences of HIV and HCV are significantly higher amongst PWID in India compared to the general population, the strains circulating within this group have not been well-characterized. Through subgenomic sequencing of viruses present in residual plasma from an HIV/HCV prevalence study conducted amongst PWID across five cities in India in 2016-2017, a total of N = 498 HCV and N = 755 HIV strains were classified from N = 975 study participants. Considerable HCV diversity was identified, with different strains predominating in each region of the country. Overall, the most common strain was genotype 3a (39.0%), with genotypes 1a (26.9%), 1b (3.0%), 1c (0.2%), 3b (20.7%), 3i (2.0%), 4a (0.2%), 4d (1.0%), 6 (1.8%), 6n (4.8%), 6 v (0.2%) and one unclassifiable recombinant specimen (0.2%) also identified. The majority of the HIV specimens were subtype C (96.7%), although subtype A (0.4%), CRF01_AE (0.4%) and unique recombinant forms (URFs, 2.5%) were also detected. Notably, the geographical restriction of HIV subtype A and CRF01_AE, and HCV genotypes 4 and 6 to specific sites suggests distinct novel introductions of HIV and HCV into PWID populations, potentially via drug trafficking routes from neighboring countries where these strains are common.


Comparing the hemodynamic effect of a large arteriovenous fistula during high and low cardiac output states.
Background: A large arteriovenous fistula (AVF) is a low-resistant circuit that affects organ perfusion and systemic hemodynamics even in standard conditions. The extent of its' effect in critical states has not been elucidated yet. We used norepinephrine to create systemic vasoconstriction, dobutamine to create high cardiac output, and rapid right ventricle pacing as a model of acute heart failure in a porcine model of high-flow AVF circulation. Methods: The protocol was performed on nine domestic female pigs under general anesthesia. AVF was created by connecting two high-diameter ECMO cannulas inserted in the femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Three interventions were performed-moderate dose of norepinephrine (0.25 ug/kg/min), moderate dose of dobutamine (10 ug/kg/min) and rapid right ventricle pacing to simulate low cardiac output state with mean arterial pressure under 60 mmHg. Measurements were taken with opened and closed arteriovenous fistula. Results: Continuous infusion of norepinephrine with opened AVF significantly increased mean arterial pressure (+20%) and total cardiac output (CO) (+36%), but vascular resistance remained virtually unchanged. AVF flow (Qa) rise correlated with mean arterial pressure increase (+20%; R = 0.97, p = 0.0001). Effective cardiac output increased, leading to insignificant improvement in organ perfusion. Dobutamine substantially increased cardiac output with insignificant effect on AVF flow and mean arterial pressure. Carotid artery blood flow increased significantly after dobutamine infusion by approximately 30%, coronary flow velocity increased significantly only in closed AVF state. The effective cardiac output using the heart failure model leading to decrease of carotid artery flow and worsening of brain and peripheral tissue oximetry. AVF blood flow also dropped significantly and proportionally to pressure, but Qa/CO ratio did not change. Therefore, the effective cardiac output decreased. Conclusion: In abovementioned extreme hemodynamic conditions the AVF flow was always directly proportional to systemic perfusion pressure. The ratio of shunt flow to cardiac output depended on systemic vascular resistance. These experiments highlight the detrimental role of a large AVF in these critical conditions' models.


Toxicity of polybrominated diphenyl ethers (DE-71) in chicken (Gallus gallus), mallard (Anas platyrhynchos), and American kestrel (Falco sparverius) embryos and hatchlings.
Embryonic survival, pipping and hatching success, and sublethal biochemical, endocrine, and histological endpoints were examined in hatchling chickens (Gallus gallus), mallards (Anas platyrhynchos), and American kestrels (Falco sparverius) following air cell administration of a pentabrominated diphenyl ether (penta-BDE; DE-71) mixture (0.01-20 microg/g egg) or polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl; 0.002 microg/g egg). The penta-BDE decreased pipping and hatching success at concentrations of 10 and 20 microg/g egg in kestrels but had no effect on survival endpoints in chickens or mallards. Sublethal effects in hatchling chickens included ethoxyresorufin-O-dealkylase (EROD) induction and histological changes in the bursa, but these responses were not observed in other species. Polychlorinated biphenyl congener 126 (positive control) reduced survival endpoints in chicken and kestrel embryos and caused sublethal effects (EROD induction, reduced bursal mass and follicle size) in chickens. Mallards were clearly less sensitive than the other species to administered penta-BDE and PCB 126. In a second experiment, the absorption of penta-BDE (11.1 microg/g egg, air cell administered during early development) into the contents of chicken and kestrel eggs was determined at various intervals (24 h postinjection, midincubation, and pipping). By pipping, 29% of the penta-BDE administered dose was present in the egg contents in chickens, and 18% of the administered dose was present in kestrel egg contents. Based on uptake in kestrels, the lowest-observed-effect level on pipping and hatching success may be as low as 1.8 microg total penta-BDE/g egg, which approaches concentrations detected in eggs of free-ranging birds. Because some penta-BDE congeners are still increasing in the environment, the toxic effects observed in the present study are cause for concern in wildlife.


Electrodermal activity in bipolar disorder: Differences between mood episodes and clinical remission using a wearable device in a real-world clinical setting.
Bipolar disorder (BD) lacks objective measures for illness activity and treatment response. Electrodermal activity (EDA) is a quantitative measure of autonomic function, which is altered in manic and depressive episodes. We aimed to explore differences in EDA (1) inter-individually: between patients with BD on acute mood episodes, euthymic states and healthy controls (HC), and (2) intra-individually: longitudinally within patients during acute mood episodes of BD and after clinical remission. A longitudinal observational study. EDA was recorded using a research-grade wearable in patients with BD during acute manic and depressive episodes and at clinical remission. Euthymic BD patients and HC were recorded during a single session. We compared EDA parameters derived from the tonic (mean EDA, mEDA) and phasic components (EDA peaks per minute, pmEDA, and EDA peaks mean amplitude, pmaEDA). Inter- and intra-individual comparisons were computed respectively with ANOVA and paired t-tests. 49 patients with BD (15 manic, 9 depressed, and 25 euthymic), and 19 HC were included. Patients with bipolar depression showed significantly reduced mEDA (p = 0.003) and pmEDA (p = 0.001), which increased to levels similar to euthymia or HC after clinical remission (mEDA, p = 0.011; pmEDA, p < 0.001; pmaEDA, p < 0.001). Manic patients showed no differences compared to euthymic patients and HCs, but a significant reduction of tonic and phasic EDA parameters after clinical remission (mEDA, p = 0.035; pmEDA, p = 0.004). Limited sample size, high inter-individual variability of EDA parameters, limited comparability to previous studies and non-adjustment for medication. EDA ecological monitoring might provide several opportunities for early detection of depressive symptoms, and might aid at assessing early response to treatments in mania and bipolar depression.


Patient computer use to prompt doctor adherence to diabetes management guidelines.
Doctor compliance with diabetic care guidelines is low and may be improved with system-wide changes that include patient involvement. The objective of this study was to determine if patients in an internal medicine teaching clinic would use a touch-screen computer to receive personalized information regarding their need for diabetes care. Outcomes included determining if this intervention would improve resident doctor compliance with diabetic guidelines. In this prospective study a computer was available for patients to use independently in one clinic, while another computer was placed in a second clinic with nursing support. Patients responding they were diabetic to the first screen received screens covering HbA1c, blood pressure, cholesterol, foot, eye examinations and compliance with having labs drawn. Non-diabetic patients received three general health screens. A response-based report was printed for patients to share with their doctor. Chart reviews were conducted to assess diabetic health care delivery. The computer was used voluntarily by 20.6% of patients in the primary clinic and by 100% of patients in the nurse-assisted clinic. A total of 104 patients from both clinics responded they were diabetic; over 50% did not know what HbA1c meant and a minority responded their HbA1c, blood pressure and cholesterol were at good levels. Significantly more HbA1c tests conducted within 6 months were documented in patients' charts. Patients used the computer effectively without direction in the primary clinic. In this initial study, implementation of the computer program increased the number of HbA1c tests ordered. Future studies incorporating refinements may increase both usage and efficacy of this intervention.


Cancer risk communication with low health literacy patients: a continuing medical education program.
Low health literacy (HL) is an important risk factor for cancer health disparities. Describe a continuing medical education (CME) program to teach primary care physicians (PCP) cancer risk communication and shared decision-making (SDM) with low HL patients and baseline skills assessment. Cluster randomized controlled trial in five primary care clinics in New Orleans, LA. Eighteen PCPs and 73 low HL patients overdue for cancer screening. Primary care physicians completed unannounced standardized patient (SP) encounters at baseline. Intervention physicians received SP verbal feedback; academic detailing to review cancer screening guidelines, red flags for identifying low HL, and strategies for effective counseling; and web-based tutorial of SP comments and checklist items hyperlinked to reference articles/websites. Baseline PCP self-rated proficiency, SP ratings of physician general cancer risk communication and SDM skills, patient perceived involvement in care. Baseline assessments show physicians rated their proficiency in discussing cancer risks and eliciting patient preference for treatment/decision-making as "very good". SPs rated physician exploration of perceived cancer susceptibility, screening barriers/motivators, checking understanding, explaining screening options and associated risks/benefits, and eliciting preferences for screening as "satisfactory". Clinic patients rated their doctor's facilitation of involvement in care and information exchange as "good". However, they rated their participation in decision-making as "poor". The baseline skills assessment suggests a need for physician training in cancer risk communication and shared decision making for patients with low HL. We are determining the effectiveness of teaching methods, required resources and long-term feasibility for a CME program.


Methicillin-Susceptible Teicoplanin-Resistant Staphylococcus haemolyticus Isolate from a Bloodstream Infection with Novel Mutations in the tcaRAB Teicoplanin Resistance Operon.
Staphylococcus haemolyticus is a coagulase-negative staphylococcus that is frequently isolated from blood cultures. Here, we report a case of methicillin-susceptible S. haemolyticus that is resistant to teicoplanin (TEC) and heteroresistant to vancomycin (VAN). The isolate was susceptible to cefoxitin and resistant to TEC by Etest. Population analysis profile-area under the curve analysis confirmed the presence of a VAN heteroresistant subpopulation. Next-generation sequencing analysis of the genome revealed the presence of blaZ and msr(A), which encode cross-resistance to macrolide, lincosamide, and streptogramin B, and the quinolone resistance-conferring gene norA. In addition, several amino acid substitutions were observed in the TEC resistance operon tcaRAB, including I3N, I390N, and L450I in tcaA and L44V, G52V, and S87P in tcaR, as well as in the transpeptidase encoding gene walK (D336Y, R375L, and V404A) and L315 and P316 in graS. We hypothesized that this combination of mutations could confer TEC resistance and reduced VAN susceptibility.


Non-rigid structure estimation in trajectory space from monocular vision.
In this paper, the problem of non-rigid structure estimation in trajectory space from monocular vision is investigated. Similar to the Point Trajectory Approach (PTA), based on characteristic points' trajectories described by a predefined Discrete Cosine Transform (DCT) basis, the structure matrix was also calculated by using a factorization method. To further optimize the non-rigid structure estimation from monocular vision, the rank minimization problem about structure matrix is proposed to implement the non-rigid structure estimation by introducing the basic low-rank condition. Moreover, the Accelerated Proximal Gradient (APG) algorithm is proposed to solve the rank minimization problem, and the initial structure matrix calculated by the PTA method is optimized. The APG algorithm can converge to efficient solutions quickly and lessen the reconstruction error obviously. The reconstruction results of real image sequences indicate that the proposed approach runs reliably, and effectively improves the accuracy of non-rigid structure estimation from monocular vision.


Pain management in knee surgery.
Thus Jefferson says, "The art of life is the art of avoiding pain." How can we possibly avoid pain either physical or psychological throughout our life span? Perhaps it is more realistic to do our best to minimize pain or manage it effectively. Managing pain throughout the preoperative and postoperative periods is achievable, but we are not always doing an adequate job. The focus of this article is to provide an opportunity to look at using appropriate medications, treatment approaches, and timing for the orthopaedic patient. The concepts of preemptive analgesia and around-the-clock (ATC) dosing are discussed.


An improved analytical model of the magnetostriction-based EMAT of SH0 mode guided wave in a ferromagnetic plate.
The accuracy of electro-acoustic energy transfer efficiency (EAETE) model directly determines the optimization results of an electromagnetic acoustic transducer (EMAT). In this study, the EMAT model of SH0 mode generation based on magnetostriction mechanism is re-examined. In the existing magnetostriction-based EMAT (MEMAT) analytical model, an approximate method of dynamic magnetic field was employed. Thus the effects of the tested ferromagnetic materials on the dynamic magnetic field in the air is ignored and the boundary condition between air and material is not exact. As a result, the calculated dynamic magnetic field inside the tested ferromagnetic materials is incorrect, thus leading to the calculation errors of magnetostriction body force and the final EAETE of MEMAT. The rigorous analytical solutions for calculating the dynamic magnetic field are derived based on Maxwell equations and boundary conditions in this study. The prediction results of improved analytical model were consistent with previously reported experimental results. Compared with existing analytical models, the improved model showed the higher prediction accuracy of several parameters, including dynamic magnetic field, magnetostriction force and the EAETE.


The regulation of fiber arrangement in advanced cellular cementogenesis of human teeth.
This study observed cellular cementum in fully formed human premolars by light and electron microscopy to elucidate how cementoblasts regulate the fiber arrangement in cementum. Cementoblasts had wing-like processes encircling the principal fibers, where Sharpey's fibers were dense. On the cementum-facing side, wing-like processes were segmented into finger-like processes in parallel with the cementum surface. Observations suggested that with the segmentation intrinsic fibers appeared around principal fibers in close association with finger-like processes. Where Sharpey's fibers were few or absent, where intrinsic fibers were the main fibrous element of the cementum, cementoblasts had only few or no wing-like processes, but had finger-like processes not associated with the wing-like processes on the cementum-facing side. On the basis of the origin of the finger-like processes the main results suggest that there are two kinds of cementoblasts: one has finger-like processes associated with wing-like processes and secretes intrinsic fibers from the finger-like processes to incorporate the principal fibers for tooth support. The second type has finger-like processes not associated with wing-like processes, this type secretes intrinsic fibers from the finger-like processes to adjust the cementum thickness.


Investigating the Association of Genetic Admixture and Donor/Recipient Genetic Disparity with Transplant Outcomes.
Disparities in survival after allogeneic hematopoietic cell transplantation have been reported for some race and ethnic groups, despite comparable HLA matching. Individuals' ethnic and race groups, as reported through self-identification, can change over time because of multiple sociological factors. We studied the effect of 2 measures of genetic similarity in 1378 recipients who underwent myeloablative first allogeneic hematopoietic cell transplantation between 1995 and 2011 and their unrelated 10 of 10 HLA-A, -B, -C, -DRB1, and-DQB1- matched donors. The studied factors were as follows (1) donor and recipient genetic ancestral admixture and (2) pairwise donor/recipient genetic distance. Increased African genetic admixture for either transplant recipients or donors was associated with increased risk of overall mortality (hazard ratio [HR], 2.26; P = .005 and HR, 3.09; P = .0002, respectively) and transplant-related mortality (HR, 3.3; P = .0003 and HR, 3.86; P = .0001, respectively) and decreased disease-free survival (HR, 1.9; P = .02 and HR, 2.46; P = .002 respectively). The observed effect, albeit statistically significant, was relevant to a small subset of the studied population and was notably correlated with self-reported African-American race. We were not able to control for other nongenetic factors, such as access to health care or other socioeconomic factors; however, the results suggest the influence of a genetic driver. Our findings confirm what has been previously reported for African-American recipients and show similar results for donors. No significant association was found with donor/recipient genetic distance.


Increased fasting plasma ghrelin levels in patients with bulimia nervosa.
Fasting plasma ghrelin levels play an important role in the pathophysiology of the eating disorder anorexia nervosa. Bulimia nervosa (BN) also has been associated with abnormal neuroendocrine regulation. Thus, we examined the relationship between body mass index (BMI) and plasma ghrelin concentrations in patients with BN for the first time. The subjects included 15 female BN patients and 11 female healthy volunteers (controls). Fasting blood samples were collected from all subjects. The plasma ghrelin concentrations in all subjects demonstrated a significantly negative correlation with BMI. Mean plasma ghrelin level in BN patients was significantly higher than that in the controls, though mean BMIs between the groups were not significantly different. These findings suggest that not only BMI but also abnormal eating behaviors with habitual binge eating and purging may have some influence on circulating ghrelin level in BN.


Novel access to azaphosphiridine complexes and first applications using Brønsted acid-induced ring expansion reactions.
Synthesis of azaphosphiridine complexes 3a-e was achieved via thermal group transfer reaction using 2H-azaphosphirene complex 1 and N-methyl C-aryl imines 2a-e (i) or via reaction of transient Li/Cl phosphinidenoid complex 5 (prepared from dichloro(organo)phosphane complex 4) using 2a-c (ii), respectively. Reaction of complexes 3a,d and trifluoromethane sulfonic acid in the presence of dimethyl cyanamide led to a highly bond- and regioselective ring expansion yielding 1,3,4sigma3lambda3-diazaphosphol-2-ene complexes 8a,d after deprotonation with NEt3. 31P NMR reaction monitoring revealed that protonation of complex 3a yields the azaphosphiridinium complex 6a, unambiguously identified by NMR spectroscopy at low temperature. All isolated products were characterized by multinuclear NMR spectroscopy, IR and UV/Vis (for 3a,d, 6a, 8a,d), MS and single-crystal X-ray crystallography in the cases of complexes 3b-d, 8a and 8d. DFT studies on the reaction mechanism and compliance constants of the model complex of 6a are presented.


Functional Diversity of Transcriptional Regulators in the Cyanobacterium Synechocystis sp. PCC 6803.
Functions of transcriptional regulators (TRs) are still poorly understood in the model cyanobacterium Synechocystis sp. PCC 6803. To address the issue, we constructed knockout mutants for 32 putative TR-encoding genes of Synechocystis, and comparatively analyzed their phenotypes under autotrophic growth condition and metabolic profiles using liquid chromatography-mass spectrometry-based metabolomics. The results showed that only four mutants of TR genes, sll1872 (lytR), slr0741 (phoU), slr0395 (ntcB), and slr1871 (pirR), showed differential growth patterns in BG11 medium when compared with the wild type; however, in spite of no growth difference observed for the remaining TR mutants, metabolomic profiling showed that they were different at the metabolite level, suggesting significant functional diversity of TRs in Synechocystis. In addition, an integrative metabolomic and gene families' analysis of all TR mutants led to the identification of five pairs of TR genes that each shared close relationship in both gene families and metabolomic clustering trees, suggesting possible conserved functions of these TRs during evolution. Moreover, more than a dozen pairs of TR genes with different origin and evolution were found with similar metabolomic profiles, suggesting a possible functional convergence of the TRs during genome evolution. Finally, a protein-protein network analysis was performed to predict regulatory targets of TRs, allowing inference of possible regulatory gene targets for 4 out of five pairs of TRs. This study provided new insights into the regulatory functions and evolution of TR genes in Synechocystis.


The performance of a resazurin chromogenic agar plate with a combined disc method for rapid screening of extended-spectrum-β-lactamases, AmpC β-lactamases and co-β-lactamases in Enterobacteriaceae.
A promising means of rapid screening of extended-spectrum-β-lactamase (ESBL), AmpC β-lactamase, and co-production of ESBL and AmpC that combines resazurin chromogenic agar (RCA) with a combined disc method is here reported. Cefpodoxime (CPD) discs with and without clavulanic acid (CA), cloxacillin (CX) and CA+CX were evaluated against 86 molecularly confirmed β-lactamase-producing Enterobacteriaceae, including 15 ESBLs, 32 AmpCs, nine co-producers of ESBL and AmpC and 30 carbapenemase producers. The CA and CX synergy test successfully detected all ESBL producers (100% sensitivity and 98.6% specificity) and all AmpC producers (100% sensitivity and 96.36% specificity). This assay also performed well in screening for co-existence of ESBL and AmpC (88.89% sensitivity and 100% specificity). The RCA assay is simple and inexpensive and provides results within 7 hr. It can be performed in any microbiological laboratory, in particular, in geographic regions in which ESBL, AmpC or co-β-lactamase-producing Enterobacteriaceae are endemic.


A nomogram to classify men with lower urinary tract symptoms using urine flow and noninvasive measurement of bladder pressure.
Bladder pressure during voiding can be estimated by a noninvasive technique using controlled inflation of a penile cuff. This test provides a valid and reliable estimate of isovolumetric bladder pressure but to our knowledge the role of the test for the routine clinical treatment of patients with lower urinary tract symptoms (LUTS) has yet to be demonstrated. As a first step, we evaluated a proposed nomogram for the diagnosis of bladder outlet obstruction in men with LUTS using noninvasive measurements of pressure and flow. Using a combination of theoretical calculation and experimental data the existing International Continence Society pressure flow nomogram was modified to allow noninvasive measurement of isovolumetric bladder pressure in place of detrusor pressure at maximum urine flow. Accuracy of the nomogram for classifying obstruction was then tested in a group of 144 men with LUTS who underwent an invasive and a noninvasive pressure flow study. The modified nomogram identified men with obstruction with 68% positive predictive value and 78% negative predictive value. Predictive accuracy could be improved by adding an additional criterion of obstruction, that is maximum urine flow less than 10 ml second, whereby an identifiable 69% of all cases could be classified as obstructed (88% positive predictive value) or not obstructed (86% negative predictive value). In the remaining 31% of patients invasive pressure flow studies would provide additional information, although some results would remain equivocal. The proposed nomogram combined with the additional flow rate criterion can classify more than two-thirds of cases without recourse to invasive pressure flow studies. We must now evaluate the usefulness of this classification for the treatment of men with LUTS.


The E3 Ubiquitin Ligase HectD1 Suppresses EMT and Metastasis by Targeting the +TIP ACF7 for Degradation.
Cancer cells exploit the epithelial-to-mesenchymal transition (EMT) program to become metastatic. Cytoskeletal regulators are required in mesenchymal cells where they promote EMT and EMT-induced migration. In a search for regulators of metastasis, we conducted shRNA screens targeting the microtubule plus-end tracking proteins (+TIPs). We show that the +TIP ACF7 is essential both for the maintenance of the EMT program and to promote migration. We find that the E3 ubiquitin ligase HectD1 promotes ACF7-proteasome-mediated degradation. Depletion of HectD1 stabilized ACF7, and this enhanced EMT and migration. Decreased HectD1 expression increased metastases in mouse models and conferred increased resistance to the cytotoxic drug cisplatin. A retrospective analysis of biopsies from breast cancer patients also reveals a correlation between higher ACF7 or lower HectD1 expression with poor clinical outcomes. Together, these results suggest that the control of ACF7 levels by HectD1 modulates EMT and the efficiency of metastasis.


Interface dermatitis in skin lesions of Kikuchi-Fujimoto's disease: a histopathological marker of evolution into systemic lupus erythematosus?
Kikuchi's disease (KD) is a self-limiting histiocytic necrotizing lymphadenitis (HNL). Cutaneous manifestations are frequent and usually show histopathological findings similar to those observed in the involved lymph nodes. HNL with superposed histological features to KD has been described in patients with lupus erythematosus (LE), and a group of healthy patients previously reported as having HNL may evolve into LE after several months. Up to date, features to predict which HNL patients will have a self-limiting disease and which could develop LE have been not identified. In order to clarify the characteristics of skin lesions associated with KD, we report a case of HNL with evolution into systemic lupus erythematosus (SLE) and a review of previous reports of KD with cutaneous manifestations. A 17-year-old woman presented with a 4-month history of fever and generalised lymphadenopathy. A diagnosis of HNL was established based on a lymph node biopsy. One month later, she developed an erythematoedematous rash on her upper body, with histopathological findings of interface dermatitis. After 8 months, anti-nuclear antibodies (ANA) at titre of 1/320, anti-DNA-ds antibodies and marked decrease of complement levels were detected. During the following 2 years, she developed diagnostic criteria for SLE, with arthralgias, pleuritis, aseptic meningitis, haemolytic anaemia and lupus nephritis. To our knowledge, 27 cases of nodal and cutaneous KD have been reported, 9 of which later developed LE. In all these patients, the skin biopsy revealed interface dermatitis. Skin biopsy revealed a pattern of interface dermatitis in all reviewed KD cases, which evolved into LE. Even this histopathological finding was not previously considered significant; it might be a marker of evolution into LE.


Long-Term Outcomes of Total Exudative Retinal Detachments in Stage 3B Coats Disease.
To evaluate the long-term outcomes of treatment of total exudative retinal detachments (ERDs) secondary to Coats disease (stage 3B) and the role of vitrectomy. Retrospective, observational case series. A total of 16 eyes in 16 patients undergoing treatment for total ERDs secondary to Coats disease with at least 5 years of follow-up. We reviewed the records of patients with stage 3B Coats disease. The interventions, including the timing of vitrectomy if used, and clinical course were recorded. The primary outcome measures were visual acuity at the most recent appointment, whether there was progression to neovascular glaucoma (NVG) or phthisis bulbi, and need for enucleation. All patients received ablative treatment (photocoagulation or cryotherapy), with 8 having scleral buckling (SB) and 6 having external drainage of subretinal fluid (XD). Of the 12 patients who had pars plana vitrectomy (PPV), 8 had early PPV (EV) in the first year after presenting, and 4 of 8 in the expectant management group had late PPV (late vitrectomy) at a mean of 4.3 years post-presentation for treatment of significant traction retinal detachment (TRD). The other 4 patients of 8 in the expectant management group did not require vitrectomy. Mean follow-up overall was 9 1/2 years. At the date of last follow-up, 50% had no light perception or light perception vision, which was consistent across the subgroups that underwent EV (4/8), late vitrectomy (2/4), or no PPV (2/4). A total of 4 of 16 patients had progression to NVG or phthisis, 1 of whom required enucleation. In this retrospective series of patients with Stage 3B Coats disease, ablative therapy with a combination of PPV, XD, or SB was effective in preventing progression to NVG or phthisis in the majority of patients, thus preserving the globe. Half of the patients (4/8) in this series who did not undergo PPV in the early vitrectomy group developed late-onset TRD, suggesting a possible role for early prophylactic vitrectomy with possible SB and XD; however, this is balanced by the other half (4/8) in the expectant management group who did not require any vitrectomy.


[A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test].
We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug.


Recanalization of an occluded major side branch after stenting with intracoronary adenosine.
Adenosine is a powerful direct coronary vasodilator with a very short half-life that has been shown to be effective in avoiding and reversing no reflow. We report an immediate successful recanalization of an occluded major side branch after stenting with acute intracoronary adenosine administration. The beneficial effect of adenosine may imply that the side branch occlusion (SBO) in this case could be due to spasm or distal embolization of the atherosclerotic debris ending up with no flow. We believe that adenosine could be helpful in at least some cases of SBO and therefore may be worth attempting.


Cellular uptake of coumarin-6 under microfluidic conditions into HCE-T cells from nanoscale formulations.
In vitro studies of ocular bioavailability of active pharmaceutical ingredients (API) from colloidal drug delivery systems do not consider physiological shear stress generated by eyelid wiping and tear flow. The present study introduces a live cell imaging approach which enables the investigation of model drug uptake from various formulations under shear stress by using custom-made microchannels for the cultivation of human corneal epithelial cells (HCE-T). Coumarin-6 (C-6) was used as a model API incorporated into solid lipid nanoparticles and liposomes, and as an aqueous crystalline suspension. Confocal laser scanning microscopy visualized C-6 uptake into HCE-T cells in a time-resolved manner with an applied shear stress of 0.1 Pa. Static conditions were also studied for comparative purposes. Additionally, solid lipid nanoparticles (SLN) were labeled with a fluorescent phospholipid to check whether C-6 uptake was associated with SLN incorporation into the cells. Intact SLN were not incorporated into the cells, i.e., C-6 was passively redistributed from SLN to lipophilic cellular compartments. C-6 was enriched up to a given limit in HCE-T cells within 5 min of contact with the dispersions both under static and under flow conditions. The C-6 delivery rate from liposomes was superior to that from SLN whereby the suspension exhibited the lowest rate. C-6 release rates were comparable for static and flow conditions. Alternate flushing with formulations and buffer revealed that cells accumulated C-6. The results suggest that combining microfluidics with live cell imaging provides a valuable option for in vitro studies of ocular drug delivery.


A Novel Rapid Sample Preparation Method for MALDI-TOF MS Permits Borrelia burgdorferi Sensu Lato Species and Isolate Differentiation.
The genus Borrelia comprises vector-borne bacterial pathogens that can severely affect human and animal health. Members of the Borrelia burgdorferi sensu lato species complex can cause Lyme borreliosis, one of the most common vector-borne diseases in the Northern hemisphere. Besides, members of the relapsing fever group of spirochetes can cause tick-borne relapsing fever in humans and various febrile illnesses in animals in tropical, subtropical and temperate regions. Borrelia spp. organisms are fastidious to cultivate and to maintain in vitro, and therefore, difficult to work with in the laboratory. Currently, borrelia identification is mainly performed using PCR and DNA sequencing methods, which can be complicated/frustrating on complex DNA templates and may still be relatively expensive. Alternative techniques such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) are not well established for Borrelia spp., although this technique is currently one of the most used techniques for rapid identification of bacteria in microbiological diagnostic laboratories. This is mainly due to unsatisfactory results obtained by use of simple sample preparation techniques and medium-contamination obscuring the mass spectra. In addition, comprehensive libraries for Borrelia spp. MALDI-TOF MS have yet to be established. In this study, we developed a new filter-based chemical extraction technique that allows measurement of high quality Borrelia spp. spectra from less than 100,000 bacteria per spot in MALDI-TOF MS. We used 49 isolates of 13 different species to produce the largest mass-library for Borrelia spp. so far and to validate the protocol. The library was successfully established and identifies >96% of used isolates correctly to species level. Cluster analysis on the sum spectra was applied to all the different isolates, which resulted in tight cluster generation for most species. Comparative analysis of the generated cluster to a phylogeny based on concatenated multi-locus sequence typing genes provided a surprising homology. Our data demonstrate that the technique described here can be used for fast and reliable species and strain typing within the borrelia complex.


Sulfinylamine metathesis at oxo metal species--convenient entry into imido metal chemistry.
The exchange of terminal metal oxo functionalities by N-organo and N-sulfonylimido functionalities via metathesis with bent, thus very reactive sulfinyl amines R-NSO and sulfinyl sulfonylamides R-SO(2)-NSO is described. It is demonstrated that in many cases sulfinyl amine metathesis offers a more convenient entry into imido complex synthesis than the much better investigated isocyanate metathesis at oxo complexes or condensation reactions with amines and silylated amines. Improved syntheses for some known key compounds and several new complexes of the type [V(NR)Cl(3)] and [M(NR)(2)Cl(2)] (M = Cr, Mo, W) are described. Emphasis is put on the synthesis of formerly unknown base free Lewis acids with electron-withdrawing N-substituents such as haloaryl and sulfonylaryl. Surprisingly, even [CrO(2)Cl(2)] is selectively transformed by sulfinylamines into aryl imido derivatives without any reduction by sulfur dioxide. The molecular structures of novel haloaryl imido complexes [Cr(NAr)(2)Cl(2)] Ar = C(6)F(5) and 2,4,6-Cl(3)C(6)H(2) as determined by X-ray crystallography are reported.


HLA-D and -DR antigens on human amniotic fluid cells. II. Heterogeneous expression of HLA-DR and other cell surface markers.
To evaluate further the feasibility of HLA typing for prenatal diagnosis, we tested human amniotic fluid cells (AFC), known to express HLA-A, -B, and -C antigens, for the presence of HLA-DR antigens using type-specific antisera in the microcytotoxicity assay and a monoclonal antibody directed against the common HLA-DR structure (cDR) in indirect immunofluorescence. Prenatal typing of HLA-DR on AFC in the microcytotoxicity test was possible in only one out of eight families studied. The detected DR2 antigen was confirmed by postnatal typings of cord blood lymphocytes. Thereafter, 23 different AFC cultures were tested with monoclonal antibodies in indirect immunofluorescence. Only six cultures were partially positive (23-35% fluorescent cells) with the monoclonal cDR antibody while all AFC cultures demonstrated strong positive fluorescence (68-100%) with a monoclonal antibody against the common HLA-A, -B, and -C structure (cHLA). These data suggest that only a small subpopulation of AFC expresses class II (HLA-DR) antigens in contrast to the nearly ubiquitous expression of class I (HLA-A, -B, and -C) antigens. Furthermore, the heterogeneous expression of cell surface antigens within the various AFC cultures was substantiated with monoclonal antibodies directed toward cell surface antigens of the OKT, OKM, and Lyt series that have been found to be characteristic for subpopulations of lymphoid and hemapoetic cells. Thus, at present, HLA-DR typing is not reliable for prenatal diagnosis.


Inflammatory potential of diet, weight gain, and incidence of overweight/obesity: The SUN cohort.
This study prospectively assessed the association of the inflammatory potential of a diet using the dietary inflammatory index (DII) with average yearly weight changes and incident overweight/obesity. Seven thousand and twenty-seven university graduates with body mass index <25 from the Seguimiento Universidad de Navarra (SUN) cohort were followed up during a median of 8.1 years. The DII, a validated tool based on scientific evidence to appraise the relationship between dietary parameters and inflammatory biomarkers, was used. A validated food-frequency questionnaire was used to assess intake of total energy, food, and nutrients, from which DII scores were calculated at baseline and after 10 years of follow-up. After a median follow-up of 8.1 years, 1,433 incident cases of overweight or obesity were observed. Hazard ratios for overweight/obesity were calculated, including multivariable time-dependent Cox regression models with repeated measures of diet. The hazard ratio for subjects in the highest quartile (most pro-inflammatory diet) was 1.32 (95% confidence interval 1.08-1.60) compared with participants in the lowest quartile (most anti-inflammatory diet), with a significant linear dose-response relationship (P = 0.004). Consistently, increases in average yearly weight gains were significantly associated with proinflammatory diets. A proinflammatory diet was significantly associated with a higher annual weight gain and higher risk of developing new-onset overweight or obesity.


Bladder outlet obstruction: etiology and evaluation.
Numerous gender-specific etiologies are responsible for bladder outlet obstruction (BOO). BOO may be induced by specific functional and anatomic causes. The resulting obstruction frequently produces lower urinary tract symptoms (LUTS). Categorizing and understanding these entities is crucial when proceeding with a LUTS evaluation as specific diagnostic modalities may then be used to fully delineate the degree of BOO and any secondary issues. Although urodynamic evaluation and pressure flow evaluation is the gold standard diagnostic tool, other modalities may also be used, including post void residual analysis, urinary flow rates, cystoscopy, and selected radiologic ones. Patient self-appraisal of symptoms using various inventories such as the American Urologic Association Symptom Index or the International Prostate Symptom Score is relevant to the initial assessment and subsequent longitudinal follow up. Analysis of secondary symptoms of obstruction in women is often performed using a subjective symptom appraisal and is determined urodynamically, assessing the pressure-flow relation during voiding. The complete assessment of LUTS arising from BOO often includes several of these modalities to fully define the obstructive impact on the individual's urinary function and quality of life.


Sensitive detection of specific cell-free DNA in serum samples from sheep with cystic echinococcosis.
Developing more sensitive methods for the diagnosis of echinococcosis is essential. In this study PCR assay for sensitive detection of specific cell-free DNA (cfDNA) of Echinococcus granulosus sensu lato in the sera of the sheep naturally infected with echinococcosis was investigated. To extract cfDNA from 35 infected sheep, the modified phenol-chloroform method was used for two different volumes (0.5 and 2 ml) of serum samples. From each extracted sample, two DNA volumes (5 and 10 μl) were amplified using both standard PCR and semi-nested PCR targeting NADH dehydrogenase subunit I. Standard and semi-nested PCR on 0.5 ml of serum samples detected Echinococcus DNA in 8 and 12 out of 35 sheep, respectively; however, using 2 ml of serum samples, they detected 24 and 27 samples. By increasing the volume of template DNA, the PCRs could detect 29 and 33 out of 35 samples. The results were confirmed by sequencing of randomly selected PCR amplicons and comparing them with GenBank databases. Larger volumes of serum for DNA extraction, greater volumes of DNA template for PCR, and employing a semi-nested PCR protocol, increased the sensitivity of PCR to 95%. This approach can also be applied to the diagnosis of echinococcosis in humans.


Gender-specific social support and resilience in nontraditional female college students.
Female college students report higher rates of stress than their male peers. Ineffective stress management contributes to a variety of concerning health outcomes. A number of factors have been shown to promote resilience to stress, such as experiencing positive social support. Few studies have examined if gender-specific social support impacts resilience. The present study investigates if gender-specific social support uniquely contributes to resilience among nontraditional college female students. Participants (N = 57) aged 21 to 54 completed an online survey assessing resilience and perceived social support from females and males. Participants with higher levels of perceived female social support reported higher levels of resilience than those with lower levels of perceived female social support. Perceived male social support was not significantly related to resilience when examined in conjunction with perceived female social support. These findings suggest that perceived female social support may uniquely contribute to resilience in nontraditional female students.


Recent advancements in the hormonal stimulation of ovulation in swine.
Induction of ovulation for controlled breeding is available for use around the world, and conditions for practical application appear promising. Many of the hormones available, such as human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) and its analogs, as well as porcine luteinizing hormone (pLH), have been shown to be effective for advancing or synchronizing ovulation in gilts and weaned sows. Each of the hormones has unique attributes with respect to the physiology of its actions, how it is administered, its efficacy, and approval for use. The timing for induction of ovulation during the follicle phase is critical as follicle maturity changes over time, and the success of the response is determined by the stage of follicle development. Female fertility is also a primary factor affecting the success of ovulation induction and fixed time insemination protocols. Approximately 80%-90% of female pigs will develop mature follicles following weaning in sows and synchronization of estrus in gilts. However, those gilts and sows with follicles that are less developed and mature, or those that develop with abnormalities, will not respond to an ovulatory surge of LH. To address this problem, some protocols induce follicle development in all females, which can improve the overall reliability of the ovulation response. Control of ovulation is practical for use with fixed time artificial insemination and should prove highly advantageous for low-dose and single-service artificial insemination and for use with frozen-thawed and sex-sorted sperm.


Continuing Education in Patient Safety: Massive Open Online Courses as a New Training Tool.
Describe the use of two massive open online courses designed to provide education on patient safety. Review follow-up evaluation data from the courses. DISCLOSURE STATEMENT: Neither the planners nor the authors have any conflicts of interest to disclose. The Nursing School of the University of Cantabria conducted a training session on patient safety through two massive open online courses (MOOCs) aimed at the general population and especially Spanish-speaking health professionals. This study aimed to analyze the profile of health professionals who have completed the courses, their degree of satisfaction, and the percentage of completion. In this retrospective and observational study, two MOOCs on clinical safety were created through an online platform (MiríadaX). Quantitative analysis of the profile of health professionals, their degree of satisfaction, and the percentage of completion was performed. A total of 12,400 students were enrolled, and the average completion rate was 32%. The profile of the average student was female, 37 years old, college educated, a nurse in a hospital, and interested in the course because it may be useful for performing her work. Fifty-five percent of students were very satisfied with the course. MOOCs are considered to be effective and easily accessible, with quality content for professional continuing education that encourages interdisciplinary work and meeting professionals from around the world.


Minimally invasive restorative dentistry: a biomimetic approach.
When providing dental treatment for a given patient, the practitioner should use a minimally invasive technique that conserves sound tooth structure as a clinical imperative. Biomimetics is a tenet that guides the author's practice and is generally described as the mimicking of natural life. This can be accomplished in many cases using contemporary composite resins and adhesive dental procedures. Both provide clinical benefits and support the biomimetic philosophy for treatment. This article illustrates a minimally invasive approach for the restoration of carious cervical defects created by poor hygiene exacerbated by the presence of orthodontic brackets.


[Allergodil eye drops in the treatment of allergic conjunctivitis].
The authors describe a group of 20 patients with symptoms of allergic conjunctivitis where for a period of 2-6 weeks twice a day into the conjunctival sac of both eyes Allergidol gtt, ophth., ASTA Medica AG FRG was administered. As to subjective sensations the authors evaluated itching, burning, the sensation of a foreign body and lacrimation, as to objective signs oedema of the eyelids, hyperaemia of the conjunctiva and papillary hypertrophy. The authors evaluated also the rate of onset of the effect, its duration and tolerance of the preparation. Subjective symptoms disappeared in 90% patients, hyperaemia of the conjunctivae and papillary hypertrophy receded in 12 patients (60%), in 8 (40%) they disappeared. Regression of subjective complaints occurred in all patients within 20 minutes, the duration of the effect was within the range of 11-13 hours in 18 patients (90%), 6-8 hours in two patients (10%). As to undesirable effects one female patient reported after administration of the eye drops a bitter sensation in the mouth, another one a burning sensation. Evidence was provided that the local H1 antihistaminic Allergodil gtt is effective in monotherapy in mild forms of allergic conjunctivitis.


Monolithic integration of fine cylindrical glass microcapillaries on silicon for electrophoretic separation of biomolecules.
We demonstrate monolithic integration of fine cylindrical glass microcapillaries (diameter ∼1 μm) on silicon and evaluate their performance for electrophoretic separation of biomolecules. Such microcapillaries are achieved through thermal reflow of a glass layer on microstructured silicon whereby slender voids are moulded into cylindrical tubes. The process allows self-enclosed microcapillaries with a uniform profile. A simplified method is also described to integrate the microcapillaries with a sample-injection cross without the requirement of glass etching. The 10-mm-long microcapillaries sustain field intensities up to 90 kV/m and limit the temperature excursions due to Joule heating to a few degrees Celsius only.


Clinical and microbiological aspects of the use of Lactobacillus rhamnosus PL1 strains in proctological patients with symptoms of chronic proctitis.
Recurrent proctitis and the symptoms associated therewith pose significant clinical problem in proctological patients. The objective of this study was to assess the impact of the probiotic Lactobacillus rhamnosus PL1 strain on the clinical presentation and composition of intestinal microbiota in patients with symptoms of proctitis in the course of hemorrhoidal disease and diverticulosis. Material consisted of 24 patients in whom no complete clinical improvement could be obtained after the treatment of the underlying disease. Subject to the assessment was the presence and the intensity of clinical symptoms as well as qualitative and quantitative changes in the composition of bacterial flora detected in the stool before, during and after a 9-week supplementation with the probiotic Lactobacillus rhamnosus PL1 strain. In the entire study group, the intensity of pain after 12 weeks was significantly lower (p=0,.011) compared to baseline; the intensity of flatulence and abdominal discomfort was reduced significantly as early as after 3 weeks, with the difference reaching a highly significant level after 12 weeks (pP<0,.0001). No significant difference was observed in the frequency of the reported episodes of diarrhea, constipation, as well as itching and burning in the anal region. As early as after 3 weeks of supplementation with the probiotic L. rhamnosus PL1 strain, significant qualitative and quantitative changes were observed in the composition of intestinal microbiota; the changes differed depending on the underlying disease. An increase in the total counts of the bacteria of Lactobacillus genus, particularly L. rhamnosus PL1 strain was observed regardless of the underlying disease. Tthe probiotic Lactobacillus rhamnosus PL1 strain appears to be useful in restoring appropriate ratios of bacterial populations in patients presenting with symptoms of proctitis in the course of the treatment of certain diseases of the lower gastrointestinal tract.


Fucoidans and fucoidanases--focus on techniques for molecular structure elucidation and modification of marine polysaccharides.
The research field of fucoidans (sulphated polysaccharides from algae) and fucoidanases was strongly developing in recent years. Several different fucoidans and a few fucoidan-degrading enzymes were isolated and characterised. A high potential is seen in the medical exploitation of the fucoidans and its degradation products. This review gives an overview about the research of the last 5 years concerning fucoidan characterisation and application as well as enzyme detection, characterisation and production.


Watermelon lycopene and allied health claims.
Presently, functional foods and nutraceuticals are gaining immense importance in the prevention of various maladies through dietary regimen module. Consumption of fruits and vegetables based diet has pursuit a range of bioactive components, especially phytochemicals targeting life threatening ailments. In this context, lycopene is an extensively studied antioxidant potentially present in watermelon, tomato, pink guava etc. Watermelon is one of the unique sources having readily available cis-isomeric lycopene. The distinctive aroma of watermelon is imparted by medium- and short-chain fatty acids along with geranial, ß-ionone and neral. Its consumption has been escalated owing to rich nutritional profile and allied health benefits. It is effective in reducing the extent of cancer insurgence, cardiovascular disorders, diabetes and macular diseases. The structural characteristics, physiochemical properties and therapeutic effects of lycopene are the limelight of the manuscript. However, further research investigations are still needed to address the health enhancing potential of watermelon lycopene.


A color test for the convenient identification of an ingested surface activating agent.
Color tests are easy, simple and inexpensive methods for the qualitative identification of chemicals. A color test was applied to the stomach contents of a forensic autopsy case. The result of the test, using bromophenol blue reagent, indicated the ingestion of a commercial cleaning product containing a cationic surface activating agent. Our findings suggest that forensic investigators should consider the additives used in commercial chemical products, such as surface activating agents, when determining the cause of death.


Comparison of US emergency departments by HIV priority jurisdiction designation: A case for geographically targeted screening in teaching hospitals.
The Ending the HIV Epidemic (EHE) Initiative targets a subset of United States (US) priority jurisdictions hardest hit by HIV. It remains unclear which emergency departments (EDs) are the most appropriate targets for EHE-related efforts. To explore this, we used the 2001-2019 National Emergency Department Inventories (NEDI)-USA as a framework to characterize all US EDs, focusing on those in priority jurisdictions and those affiliated with a teaching hospital. We then incorporate multivariable regression to explore the association between ED characteristics and location in an HIV priority jurisdiction. Further, to provide context on the communities these EDs serve, demographic and socioeconomic information and sexually transmitted infection case rate data were included. This reflected 2019 US Census Bureau data on age, race, ethnicity, and proportion uninsured and living in poverty along with 2001-2019 Centers for Disease Control and Prevention case rate data on chlamydia, gonorrhea, and syphilis. We found that EDs in priority jurisdictions (compared to EDs not in priority jurisdictions) more often served populations emphasized in HIV-related efforts (i.e., Black or African American or Hispanic or Latino populations), communities with higher proportions uninsured and living in poverty, and counties with higher rates of chlamydia, gonorrhea, and syphilis. Further, of the groups studied, EDs with teaching hospital affiliations had the highest visit volumes and had steady visit volume growth. In regression, ED annual visit volume was associated with an increased odds of an ED being located in a priority jurisdiction. Our results suggest that geographically targeted screening for HIV in a subset of US priority jurisdiction EDs with a teaching hospital affiliation could be an efficient means to reach vulnerable populations and reduce the burden of undiagnosed HIV in the US.


Enantiomeric determination of amphetamines: exploring a novel one-step solid-phase microextraction-based approach.
The recent advances in fiber manufacturing technology, solid-phase microextraction (SPME) is now widely studied for its effectiveness for the pretreatment of various categories of samples. This study explores a novel SPME approach for enantiomeric analysis of amphetamines, in which absorption/derivatization are accomplished in one step. Specifically, (S)-(-)-N-(Trifluoroacetyl)-prolyl chloride was adopted as the chiral derivatizing reagent and added directly into the sample matrix. Analytical parameters, such as temperature, absorption/desorption duration, and the amount of derivatizing reagent, were studied to determine their effects on the yield of analytes. The derivatization products resulting from this study show excellent desorption characteristics on the polydimethylsiloxane-coated fiber adopted in this study. Optimal operational parameters (absorption: 70 degrees C for 10 min; injection: 250 degrees C for 5 min) cause minimal negative impact on the fiber, allowing repeated use of the fiber for more than 30 times. For quantitation, data were collected under selected ion monitoring (SIM) mode using m/z 237 and 251 to designate derivatized amphetamine and methamphetamine. This method was evaluated and proved to be effective in (a) quantitative determination of the enantiomeric pairs of amphetamine and methamphetamine--in terms of repeatability, linearity, and limits of detection and quantitation; and (b) generating case-specimen data comparable to those derived from a conventional Liquid-liquid extraction approach. Good linearity for the calibration curves were established in the range of 1000-50 ng/mL for both analytes. The limits of detection for these analytes were 30 ng/mL.


Role of Postoperative Stimulated Thyroglobulin as Prognostic Factor for Differentiated Thyroid Cancer in Children and Adolescents.
Prognostic factors are essential for risk stratification in patients with differentiated thyroid carcinoma (DTC). The role of stimulated postoperative thyroglobulin (sPOTg) has been well established in adult DTC population, but it remains unclear in children and adolescents. This study aimed to evaluate potential prognostic factors in children and adolescents with DTC, with special emphasis on sPOTg analysis. Individuals aged ≤18 years at diagnosis were selected from a cohort of DTC patients attending the thyroid clinic of a tertiary university-based hospital. Baseline clinical and oncological characteristics, interventions, disease status, and outcomes were obtained from medical records. Clinical variables included in the univariate analysis were sex, age at diagnosis, tumor size, the presence of lymph node and distant metastasis, and sPOTg. Additionally, sPOTg was evaluated using the area under the receiver operating characteristic curve analysis. Thirty-two children and adolescents with DTC (28 girls, 87.5%; the mean age at diagnosis = 14.7 ± 3.2 years) were included in this study. Thirty-one (96.9%) patients had papillary thyroid carcinoma. The median tumor size was 2.0 cm (P25-75 = 1.6-3.5), 22 patients (68.8%) had lymph node disease, and 5 (15.6%) had distant metastasis at diagnosis. All patients underwent total thyroidectomy, and 29 (90.6%) received radioactive iodine therapy. After a median follow-up of 5.0 years (P25-75 = 2.0-10.0), disease status was available for 27 patients: 15 (55.6%) patients were disease free, six (22.5%) had biochemical disease, and six (22.2%) had persistent structural disease (two cervical and four distant metastasis). Prognostic factors associated with persistent disease in the univariate analysis were lymph node and distant metastasis at diagnosis and sPOTg. According to the receiver operating curve analysis (n = 17 patients), the best sPOTg cutoff to predict disease-free status was 31.5 ng/mL, with a sensitivity and specificity of 100%. The data demonstrate that sPOTg displayed high accuracy in predicting the risk of persistent disease in young patients with DTC.


Women's body dissatisfaction, physical appearance comparisons, and Instagram use throughout the COVID-19 pandemic: A longitudinal study.
This study aimed to determine the evolution of Instagram use, body dissatisfaction and physical appearance comparisons throughout the coronavirus disease-2019 (COVID-19) pandemic, and to explore whether there was a relationship between the changes in Instagram use throughout the pandemic and body dissatisfaction and physical appearance comparisons. A total of 272 Spanish women (16-70 years old) were followed-up across four waves of assessment between November 2019 (before the pandemic started) and July 2021. Body dissatisfaction, social appearance comparisons, and Instagram use were assessed using the Eating Disorders Inventory-3, the Physical Appearance Comparison Scale-Revised, and an ad hoc questionnaire for Instagram use, respectively. No statistically significant changes were found in the frequency of Instagram use, nor on the proportion of women following appearance-focused accounts on Instagram, among the data collection periods. Body dissatisfaction significantly increased from T1 to T4, and physical appearance comparisons significantly increased from T1 to T2, T3, and T4. These increases were not found to be significant for those with eating disorder risk. No significant differences were found in body dissatisfaction and physical appearance comparisons depending on whether participants' frequency of Instagram use had changed or remained the same, or whether they had started/stopped/continued following appearance-focused accounts on Instagram during the pandemic. Women's body dissatisfaction and physical appearance comparisons seem to have increased throughout the pandemic. The experiences of individuals with eating disorder risk throughout the pandemic, and the relationship between the pandemic and Instagram use, might be complex and need further research. This study suggests that women's body dissatisfaction and physical appearance comparisons have increased throughout the COVID-19 pandemic. However, this increase might not be as clear for those who had eating disorder risk before the pandemic. Instagram frequency of use, and the percentage of women following appearance-focused accounts on Instagram, do not seem to have significantly increased. More research is needed to explore the impact of the pandemic.


Web-based strategies to disseminate a sun safety curriculum to public elementary schools and state-licensed child-care facilities.
The Sunny Days, Healthy Ways curriculum, which has been effective in previous trials, was disseminated to public elementary schools (n=2,030) and state-licensed child-care facilities (n=3,755) in 4 states. Two Web sites were created, varying in the amount and type of information. Mailings referred principals and directors to the sites. Overall 117 unique users made 172 visits to the sites. More repeat visits were made to the enhanced than to the basic site (p=.04). In a survey, 20.0% of principals and directors recalled receiving the mailings and 80.9% of these read them. Web-based strategies were weak, but the low response rate may be typical for such marketing. They will require supplementation by more personal approaches.


[Analysis of community colorectal cancer screening in 50-74 years old people in Guangzhou, 2015-2016].
Objective: To analyze the effect of colorectal cancer screening in the general population in Guangzhou, and provide evidence for the for development of colorectal cancer screening policy and strategy. Methods: The data of colorectal cancer screening in Guangzhou during 2015- 2016 were collected. The participation, the positive rate of fecal occult blood test, the detection rate of colonoscopy and screening effect of colonoscopy were evaluated. Results: A total of 220 834 residents aged 50-74 years received the screening, and the positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively. The detection rates of all colorectal lesions were higher in men than in women (all P<0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer cases were found, accounting for 46.26% of the total cases. The overall screening detection rate of colorectal cancer was 104.15/100 000, higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance (P<0.001), but age group <70 years had higher detection rate, age group ≥70 years had higher incidence rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk, increase the detection rate of colorectal lesions, early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer. The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years. It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.


Vertical migration in the soil of Cr(VI) and chromite ore processing residue: Field sampling and benchtop simulation.
Chromite ore processing residue (COPR) keeps releasing Cr(VI) over time, and the mixing of residual COPR into soil makes the remediation of COPR-contaminated sites challenging. In this study, a sample of COPR and two soil profiles were collected from a typical historical COPR-contaminated site, and the vertical migration of Cr(VI) and COPR particles in contaminated soil was simulated in the laboratory. Cr(VI) was detected in the upper layer of the field samples at thousands of milligrams per kilogram even after decades of aging, and it can be leached out and migrate vertically deep into the surrounding soil and groundwater. In the COPR-containing soil, more diverse hydrated minerals of brownmillerite were produced than the COPR in the open air on the site. Minerals with high Cr content in COPR-containing soils have a relatively high proportion of particles smaller than 10 µm. COPR particles smaller than 5 µm were found to have migrated downward into the deep soil. During simulated one-year of precipitation, 578.9 mg Cr(VI)/kg was leached from COPR, while 35.5% of the COPR particles smaller than 5 µm had the potential to migrate vertically. The management of COPR particles should be emphasized during risk management or remediation of COPR-contaminated sites.


A Solvothermal Synthesis of TiO₂ Nanoparticles in a Non-Polar Medium to Prepare Highly Stable Nanofluids with Improved Thermal Properties.
Nanofluids are systems with several interesting heat transfer applications, but it can be a challenge to obtain highly stable suspensions. One way to overcome this challenge is to create the appropriate conditions to disperse the nanomaterial in the fluid. However, when the heat transfer fluid used is a non-polar organic oil, there are complications due to the low polarity of this solvent. Therefore, this study introduces a method to synthesize TiO₂ nanoparticles inside a non-polar fluid typically used in heat transfer applications. Nanoparticles produced were characterized for their structural and chemical properties using techniques such as X-ray Diffraction (XRD), Raman spectroscopy, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). The nanofluid showed a high stability, which was analyzed by means of UV-vis spectroscopy and by measuring its particle size and ζ potential. So, this nanofluid will have many possible applications. In this work, the use as heat transfer fluid was tested. In this sense, nanofluid also presented enhanced isobaric specific heat and thermal conductivity values with regard to the base fluid, which led to the heat transfer coefficient increasing by 14.4%. Thus, the nanofluid prepared could be a promising alternative to typical HTFs thanks to its improved thermal properties and high stability resulting from the synthesis procedure.


Do poverty programs alleviate poverty? The case of the Mexican National Solidarity Program.
In recent years, compensatory poverty programs have been adopted in several countries in response to the social and political effects of structural adjustment programs implemented by most Latin American and African countries. The authors analyze the Mexican National Solidarity Program "Pronasol," often cited as an exemplary social compensation program, by inquiring into its impact on poverty. The authors first investigate the relationship between structural adjustment and the process of impoverishment, in order to establish the dynamics and magnitude of poverty in Mexico. They find that the structural adjustment program has considerably increased poverty, mainly through a sustained wage decrease and job losses. The authors next discuss whether Pronasol complies with the requisites of a program that warrants a social minimum for the poor, and whether the resource allocation complies with objective criteria of the sociogeographic distribution of poverty. The data suggest that Pronasol cannot be considered to guarantee a social minimum for the poor, given the magnitude of poverty, the scarce resources allocated, the orientation of the subprograms, and the regional distribution of funds. Nor does it qualify as a social compensation program of any importance. Finally, an alternative interpretation of Pronasol is offered in the field of legitimation and political control.


The role of placental urokinase inhibitor in toxemia of pregnancy.
The fibrinolysis of the uterus can be reversed during the course of pregnancy. The chief cause of this physiologic change is an increase of urokinase (UK) inhibitor in the placenta. The UK inhibitor also has a pathologic aspect that can influence the course of pregnancy. We have proven that the hypofibrinolysis of toxemic pregnant urine results from increased UK inhibitor. Furthermore, we have shown the existence of UK inhibitor in toxemic pregnant serum and the glomerulus. On the basis of these facts we propose that UK inhibitor leaks into the maternal blood stream from the placenta and inhibits the fibrinolytic activity of UK, forming microthrombuses in the glomerulus. Excess UK inhibitor in the placenta also suppresses the fibrinolytic activity of placental plasminogen activator (PPA). Thus microthrombuses are apt to be formed in both the placenta and glomerulus. Such pathologic inhibition of fibrinolysis strongly influences the course of toxemia.


Iodine Storage and Metabolism of Mild to Moderate Iodine-Deficient Pregnant Rats.
Severe iodine deficiency during pregnancy results in neurodevelopmental disorders in children, while the consequences of mild to moderate iodine deficiency (MMID) are uncertain. The concentration of iodine in the thyroid is the most accurate indicator of iodine nutrition. This study aimed to evaluate whether the iodine stores in the thyroid cover the needs of the mother and the fetus in iodine-sufficient and MMID conditions by inductively coupled plasma-mass spectrometry. One hundred four-week-old female Wistar rats were randomly divided into MMID (low iodine intake [L]) and normal (normal iodine intake [N]) groups. The rats were fed for the next three months, and after pregnancy they were further divided into two subgroups, respectively: low iodine pregnancy (LP) and low iodine pregnancy with iodine supplement (LP+), and normal iodine intake pregnancy (NP) and normal iodine intake pregnancy with iodine supplement (NP+). The iodine intake of pregnant rats in the NP+ and LP+ groups was twice as much as in the NP and LP groups. The rats were sacrificed on gestational day 15 and postnatal day 7. The iodine concentration in the thyroid of the maternal and newborn rats, maternal serum, placenta, and amniotic fluid were determined by inductively coupled plasma-mass spectrometry. The concentration of iodine in the thyroid of the N group was significantly higher than that in the L group before pregnancy. The concentration of iodine in the maternal thyroids of the LP group decreased during pregnancy, whereas that of the NP group did not change significantly. There was no significant difference in the iodine concentration in the thyroid of mothers and offspring between the NP and NP+ groups, but it was significant between LP and LP+ groups. The concentration of iodine in amniotic fluid was significantly different between the four groups. There is sufficient iodine storage in the thyroid of maternal rats with normal iodine intake during pregnancy, and there is no need for iodine supplementation. However, iodine stores are insufficient in rats with MMID. Iodine supplementation can increase the iodine concentration in the thyroid of maternal rats with MMID and their offspring, as well as in the amniotic fluid during pregnancy.


Varicella-related deaths among adults--United States, 1997.
During January-April 1997, state health departments reported three fatal cases of varicella (chickenpox) to CDC. All three cases occurred in young adult women who were unvaccinated and susceptible to varicella and who were infected by exposure to unvaccinated preschool-aged children with typical cases of varicella. This report summarizes these three cases, which indicate that preventable varicella-related deaths continue to occur in the United States. In addition, the report re-emphasizes the recommended strategies for preventing varicella.


Exploring the Impacts of Housing Condition on Migrants' Mental Health in Nanxiang, Shanghai: A Structural Equation Modelling Approach.
Although rapid urbanization and associated rural-to-urban migration has brought in enormous economic benefits in Chinese cities, one of the negative externalities include adverse effects upon the migrant workers' mental health. The links between housing conditions and mental health are well-established in healthy city and community planning scholarship. Nonetheless, there has thusfar been no Chinese study deciphering the links between housing conditions and mental health accounting for macro-level community environments, and no study has previously examined the nature of the relationships in locals and migrants. To overcome this research gap, we hypothesized that housing conditions may have a direct and indirect effects upon mental which may be mediated by neighbourhood satisfaction. We tested this hypothesis with the help of a household survey of 368 adult participants in Nanxiang Town, Shanghai, employing a structural equation modeling approach. Our results point to the differential pathways via which housing conditions effect mental health in locals and migrants. For locals, housing conditions have direct effects on mental health, while as for migrants, housing conditions have indirect effects on mental health, mediated via neighborhood satisfaction. Our findings have significant policy implications on building an inclusive and harmonious society. Upstream-level community interventions in the form of sustainable planning and designing of migrant neighborhoods can promote sense of community, social capital and support, thereby improving mental health and overall mental capital of Chinese cities.


Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer's Disease.
BACKGROUND Our study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) which can serve as potential biomarkers for diagnosis and therapy of Alzheimer's disease (AD). MATERIAL AND METHODS We performed miRNA and mRNA integrated analysis (MMIA) to identify DEGs and DEmiRNAs of AD. The AD-specific DEmiRNAs-targets interaction network was contrasted. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Q-RT-PCR was used to verify the expression of selected DEGs and DEmiRNAs. RESULTS We conducted MMIA of AD based on 1 miRNA dataset and 3 mRNA datasets derived from the Gene Expression Omnibus (GEO) database; 1759 DEGs and 12 DEmiRNAs were obtained. DEGs of AD were significantly enriched in Huntington's disease and AD. LRP1, CDK5R1, PLCb2, NDUFA4, and DLG4 were 5 DEGs regulated by 4 DEmiRNAs, including miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. These 4 miRNAs were the top 4 miRNAs covering most DEGs. According to the qRT-PCR results, the expression of PLCβ2, NDUFA4, DLG4, miR-107, and miR-103a-3p was consistent with our integrated analysis. CONCLUSIONS We concluded that LRP1, CDK5R1, PLCβ2, NDUFA4, and DLG4 may play a role in AD regulated by miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. Our findings will contribute to identification of biomarkers and new strategies for drug design for AD treatment.


Clinical outcome of a patient with lysosomal acid lipase deficiency and first results after initiation of treatment with Sebelipase alfa: A case report.
We report on a case of very rare autosomal recessive cholesteryl ester storage disease due to lysosomal acid lipase deficiency (LALD). LALD is caused by mutations in the lysosomal acid lipase A (LIPA) gene resulting in cholesteryl ester accumulation in liver, spleen, and macrophages. It can lead to liver failure, accelerated atherosclerosis and premature death. Until recently, treatment options were limited to lipid-lowering medications to control dyslipidemia. Presently, a long-term enzyme replacement therapy with Sebelipase alfa, a recombinant human lysosomal acid lipase, is available for patients with LALD. Our patient's condition became conspicuous at the age of two due to a xanthogranuloma of the chin together with increased lipid levels, elevated liver enzymes and hepatomegaly. It took another five years until our patient was diagnosed with LALD after genetic testing. A bi-weekly therapy with intravenous Sebelipase alfa was started at the age of 26 years. It led to normalization of lipid levels, reduction of liver enzymes and beginning regression of hepatomegaly in the absence of adverse drug reactions after 46 infusions. Since LALD can take a fatal course even in patients with a long-term stable condition, it is essential to identify affected patients early and to treat them appropriately by enzyme replacement therapy. LALD should be suspected in patients with low high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) in conjunction with elevated liver enzymes or hepatomegaly. A registry for LALD patients shall help to advance our understanding of the disease as well as improve patient care (NCT01633489).


Detection of two forms of GP330. Their role in Heymann nephritis.
Heymann nephritis is characterized by glomerular immune deposits that contain a glycoprotein called gp330. The deposits are believed to result from shedding of immune complexes formed on podocytes. Complexes are also shed from proximal tubule cells, when antibodies combine with gp330 on the cell surface. We performed the present study to investigate what portion of the gp330 molecule is shed, using a rabbit antiserum against a peptide deduced to be in the cytoplasmic domain of gp330, as well as a rabbit antiserum and two monoclonal antibodies that recognize extracellular epitopes of gp330. The anti-cytoplasmic peptide antiserum precipitated from Fx1A (a crude renal cortical membrane preparation), a protein with a mass of about 440 kd that was reactive with two monoclonal anti-gp330 antibodies. (In our experiments, the protein called gp330 generally has a mass estimated to be about 440 kd.) The anti-cytoplasmic peptide antiserum also reacted with a truncated gp330 protein produced in transfected COS cells. Immunohistochemical studies showed that all the antibodies recognized the same group of epithelial cells. However, as seen in immunoultrastructural studies of proximal tubules, the anti-cytoplasmic peptide antiserum reacted only with components at the base of microvilli, whereas the anti-gp330 ectodomain antibodies identified material not only at the base, but over the surface of microvilli as well. In rats with Heymann nephritis, glomerular deposits and material shed into tubule lumens reacted with antibodies against extracellular epitopes of gp330, but not with the anti-cytoplasmic peptide antiserum. We propose that there are two forms of gp330 on the cell surface of proximal renal tubules. One form is restricted to coated pit regions at the base of microvilli and has a cytoplasmic domain containing a sequence deduced from a partial complementary DNA encoding gp330. The other form is present over microvilli (and possibly at the base of microvilli as well) and lacks the cytoplasmic domain deduced from the complementary DNA. The complexes that are shed in Heymann nephritis contain either a portion of gp330 cleaved from the full-length molecule or a form of gp330 that lacks the cytoplasmic domain.


[Complex I and IV deficits in the mitochondrial respiratory chain in two siblings with type I glutaric aciduria].
We report two brothers with a glutaric aciduria type I (GA-I) identified by Glutaryl-coenzyme A dehydrogenase deficiency in skin fibroblasts. The onset of neurologic abnormalities was at 6 and 9 months of age as an acute Reye-like presentation in one. Because of the hyperlactacidemia, hyperlactatorrachia, mitochondrial abnormalities in muscular cells and a deficiency in complex I and IV of the respiratory chain in isolated mitochondria from muscle, a presumptive diagnosis of Leigh syndrome was made. We analyze the difference between both disorders. GA-I should be suspected in patients with acute dystonia and psychomotor regression, lactic acidosis and hypodensity of the basal ganglia.


Reactive trityl derivatives: stabilised carbocation mass-tags for life sciences applications.
The rational design of novel triarylmethyl (trityl)-based mass tags (MT) for mass-spectrometric (MS) applications is described. We propose a "pK(R+) rule" to correlate the stability of trityl carbocations with their MS performance: trityls with higher pK(R+) values ionise and desorb better. Trityl blocks were synthesised that have high pK(R+) values and are stable in conditions of MS analysis; these MTs can be ionised by matrix as well as irradiation with a 337 nm nitrogen laser. (13)C-Labelled tags were prepared for MS quantitation applications. Moreover, the tags were equipped with a variety of functional groups allowing conjugation with different functionalities within (bio)molecules to enhance the MS characteristics of the latter. The MS behaviour of model polycationic trityl compounds with and without the matrix was studied to reveal that poly-trityl clusters are always singly charged under the (MA)LDI-TOF conditions. Several peptide-trityl conjugates were prepared and comparisons revealed a beneficial effect of trityl tags on the conjugate detection in MS. Trityl compounds containing para-methoxy- and dimethylamine groups, as well as a xanthene fragment, showed considerable enhancement in MS detection of model peptides; thus they are promising tools for proteomic applications. Dimethoxytrityl derivatives allow one to distinguish between Arg- and Lys-containing peptides. Maleimido trityl derivatives are suitable for the efficient derivatisation of thiol-containing peptides in pyridine.


Oncolytic virus-induced cell death and immunity: a match made in heaven?
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers. Thus, cancer therapies based on a different mechanism of action should be explored. The immune system plays an important role in keeping tumor growth at bay. However, in many cases, these responses are not strong enough to keep tumor growth under control. Thus, immunotherapy aims to boost the immune system to suppress tumor growth efficiently. This has been demonstrated by the recent successes of immune checkpoint therapy in several cancers. Oncolytic viruses (OVs) are another exciting class of immunotherapy agent. As well as replicating selectively within and killing tumor cells, OVs are able to elicit potent anti-tumor immune responses. Therapeutic vaccination with OVs, also referred to as cancer virotherapy, can thus be tailored to elicit vigorous cellular immune responses and even target individual malignancies in a personalized manner. In this review, we will describe the intricate link among oncolytic virotherapy, tumor immunology, and immunogenic cell death (ICD) and discuss ways to harness optimally their potential for future cancer therapy.