Adherence to hypertension treatment guidelines in state facilities in KwaZulu-Natal, South Africa.
Rationale, aims and objectives The province of KwaZulu-Natal, South Africa, embarked on the Essential Drugs Programme (EDP) consisting of standard treatment guidelines (STGs) and essential drugs lists in May 1999. The use of these tools was aimed at promoting rational drug use. This study sought to determine the percentage of compliance to the STGs of the EDP in the treatment of hypertension in patients in the district of eThekwini. Methods A retrospective cross-sectional randomized sampling of 100 prescriptions for hypertension per 21 health facility was conducted for the period of 3 months in 2007. Each prescription was assessed against modified World Health Organization indicators to determine compliance to STGs. Results The mean age of the sample was 55.235 years (+/-0.62). Hypertension featured as the most common diagnosis in the sample (57.5%). The mean result of compliance to the STGs for the eThekwini District was 22.05% (+/-20.03). The results of the multiple linear regression equation suggest that the variables selected in this study explain 86.79% of the variables impacting on treatment guideline adherence. Conclusion The low mean results for compliance to the STGs was due mainly to the absence of a diagnosis recorded on the prescription, and the addition of a new drug for each symptom without due consideration of polypharmacy, drug-disease and drug-drug interactions.


Patients With Mitochondrial Disease Have an Inadequate Nutritional Intake.
Mitochondrial disease (MD) is a group of disorders caused by dysfunctional mitochondria, the organelles that generate energy for the cell. Malnutrition in patients with MD may lead to increased mitochondrial dysfunction, which may enhance already existing symptoms. The aim of this study was to investigate whether patients with MD have an insufficient or unbalanced food intake and to establish which nutrients and product groups are particularly compromised in this patient group. In this observational, cross-sectional, retrospective study, sixty 3-day nutrition diaries of adult patients with MD were analyzed and compared with the Dutch recommended daily allowance and the Dutch National Food Consumption Survey (DNFCS). The intake of all macronutrients and micronutrients of patients with MD was significantly different from Dutch recommended daily allowance values with the exception of fat and iron. In particular, protein and calcium intake in patients with MD was significantly lower when compared with the DNFCS. Interindividual differences were high. Also, intake of fiber, sugars, saturated fat, and vitamin D differed from recommendations for the overall population. In comparison with DNFCS, the intake of dairy products and drinks was significant lower in patients. Our study demonstrates that many patients with MD have an inadequate diet. Specifically, intake of protein, calcium, dairy products, and fluids were low. Overall, eating a healthy diet seems as difficult for patients with MD as for the general population. Since interindividual differences are high, individual diet counseling is recommended for all adult patients with MD.


Duration of antibiotic therapy after preterm premature rupture of fetal membranes.
This study was undertaken to compare the efficacy of 3 days versus 7 days of ampicillin in prolonging gestation for at least 7 days in women with preterm premature rupture of membranes (PPROM). We performed a randomized clinical trial comparing 3 days of ampicillin with 7 days ampicillin in patients with PPROM. Our primary outcome was the prolongation of pregnancy for at least 7 days. Secondary outcomes included rates of chorioamnionitis, postpartum endometritis, and neonatal morbidity and mortality. Forty-eight patients were randomly selected. There was no statistically significant difference in the ability to achieve a 7-day latency (relative risk 0.83, 95% CI 0.51-1.38). In addition, there was no statistically significant difference in the rates of chorioamnionitis, endometritis, and our composite neonatal morbidity. In patients with PPROM, length of antibiotic therapy does not change the rate of a 7-day latency or affect the rate of chorioamnionitis, postpartum endometritis, or neonatal morbidity.


Assessment and attitude of university students about elderly: Preliminary Study.
Aims: The aim of this study was to evaluate the attitude of dental students towards elderly patients. This approach might increase the responsiveness and need of the geriatric dental education within the undergraduate dental students curriculum, which is the persistent necessity for today communities. Methods & Materials: A cross-sectional study was conducted on 201 students who were randomly selected. The investigation was carried out in Qazvin University of Medical Sciences. The attitude of dental students towards elderly was measured with a self-administered questionnaire consisting of an Aging Semantic Differential scale (ASD), which was developed by Rozencranz and Mc Nevin. Results: According to the findings of this study, the students' attitude remained very positive towards the elderly patients as they showed a strong demand to work with elderly patients. This consisted of a 24 bipolar pair of adjectives that described the attributes of behavioral characteristics thought to be applicable to persons of all ages. Conclusion: According to our finding, the future geriatric dentistry is not towards a weak point in Iran as compared with the undesirable attitudes of dental students in the developed countries.


Association of retinal layer measurements and adult cognitive function: A population-based study.
To quantify the associations of peripapillary retinal nerve fiber layer (pRNFL) thickness and macular ganglion cell layer (mGCL) volume with cognitive functioning and to investigate how demographic and vascular health factors affect these associations in a population-based sample of adults. The sample included the first 3,000 participants (age range 30-95 years) of the Rhineland Study (recruited from March 2016 to December 2018) who underwent spectral-domain optical coherence tomography and cognitive assessment at 1 of 2 identical study centers in Bonn, Germany. We used multiple linear regression models to examine the relationships between retinal layer measurements and cognitive functioning after adjustment for confounders, and we examined the moderating effects of demographic and vascular health factors. The analytical sample included 2,483 participants who were 54.3 years old (SD 13.8 years) on average. After full adjustment, each 1-SD decrease in mGCL volume was associated with a greater decrease in global function than that of pRNFL thickness (β = -0.048 [95% confidence interval (CI) -0.077 to -0.018] vs β = -0.021 [95% CI -0.049 to 0.007]). These relationships increased in strength with advancing age, were stronger in participants with hypertension, and were reversed in current smokers relative to nonsmokers. mGCL volume is more strongly related to adult cognitive functioning than pRNFL thickness, making it a better potential biomarker of neurodegeneration. Age and vascular health factors play important roles in determining the strength and direction of this association.


Sports activity after total joint arthroplasty: recommendations for the counseling physician.
Sports activity after total joint arthroplasty (TJA) has become an increasingly important topic, as many younger patients seeking TJA have higher postoperative expectations with regard to return to athletic activity. Our current knowledge of this area is largely based on retrospective clinical studies and surveys of surgeon recommendations. The decision to participate in sports after TJA depends on the patient's general health, prior athletic experience, type of TJA, and desired sporting activity. Ultimately, patients should discuss these factors with their physician in order to make an educated decision regarding sports activity after TJA. This article summarizes the best available evidence to help guide physicians in their conversation with patients regarding safe and appropriate sports activity after TJA.


Evaluation of the IMPACT blood pressure program.
To evaluate the incremental effectiveness of a work-site blood pressure control program, we conducted a randomized, controlled trial at four work sites with established health promotion programs. Workers with blood pressures of 140/90 mm Hg or higher were eligible. Eighty subjects were assigned to receive a referral to a community physician, monthly 10-minute work-site counseling sessions including blood pressure readings, and personalized mailings, whereas 79 control subjects received only a physician referral. Results for 74 intervention and 71 control subjects were obtained after 1 year. As compared with control subjects, intervention subjects experienced average declines of 8.5/3.9 mm Hg. Adjusted for age, sex, and baseline blood pressure, the decreases were 7.6 mm Hg for systolic and 2.4 mm Hg for diastolic blood pressure. These results suggest that counseling of high-risk persons and personalized mailing programs can have an incremental benefit in controlling blood pressure.


Excitonic Circular Dichroism of Chiral Quantum Rods.
As an emerging type of optically active materials, chiral molecules-stabilized semiconductor quantum dots (QDs) have achieved extensive attention. Unfortunately, understanding of the optical characteristics of chiral QDs observed by circular dichroism (CD) spectroscopy remains a great challenge due to their rather weak signals. Herein, we successfully achieve much enhanced CD responses from l- or d-cysteine-stabilized wurtzite CdSe quantum rods (QRs) thanks to their unique optical anisotropy. Furthermore, the optical activity of CdSe QRs is explored to be improved and subsequently become stable with the geometrical aspect ratio (AR) increasing, and such change matches well with alternation of the polarization factor of CdSe QRs. A non-degenerate coupled-oscillator (NDCO) model is established to elucidate the optical activity of chiral QRs, and the positive and negative natures of the CD peaks appearing at the first exciton band are clearly assigned to different transition polarization along 4pz,Se → 5sCd and 4p(x,y),Se → 5sCd, respectively. This work opens the door toward comprehension and design of optically active semiconductor nanomaterials.


Pilocytic astrocytoma: a disease with evolving molecular heterogeneity.
Pilocytic astrocytoma, the most common pediatric brain tumor, is a clinically and molecularly heterogeneous disease that occurs most often in the cerebellum and hypothalamic and chiasmatic regions. Classically, pilocytic astrocytomas are driven by the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Recently described genetic aberrations involving this pathway are critical for tumorigenesis. Tandem duplication of 7q34 encodes BRAF and produces several KIAA1549-BRAF novel oncogenic fusions. Activating point mutations of BRAF, such as BRAF (V600E), also lead to pilocytic astrocytoma. Loss of the NF1 gene allows hyperactivation of the oncogene KRAS. In this review, we discuss the current understanding of the novel molecular aberrations described in pilocytic astrocytomas and their clinical relevance for prognosis and treatment. The prognostic indications of these aberrations are discussed with regard to tumor location, tumor pathology, and patient age. A better understanding of the evolving molecular heterogeneity of pilocytic astrocytomas offers hope for developing molecularly targeted therapeutic armamentariums.


Secretion of human epidermal growth factor (EGF) in autotrophic culture by a recombinant hydrogen-utilizing bacterium, Pseudomonas pseudoflava, carrying broad-host-range EGF secretion vector pKSEGF2.
We constructed the broad-host-range human epidermal growth factor (EGF) secretion plasmid pKSEGF2 by inserting the Escherichia coli tac promoter, the signal sequence of Pseudomonas stutzeri amylase, and the synthesized EGF gene into the broad-host-range vector pKT230. E. coli JM109 carrying pKSEGF2 secreted EGF into the periplasm and the culture medium under the control of the tac promoter. Pseudomonas aeruginosa PAO1161 carrying pKSEGF2 and Pseudomonas putida AC10 carrying pKSEGF2 secreted EGF into the culture medium constitutively. Four hydrogen-utilizing bacteria, Pseudomonas pseudoflava, Alcaligenes eutrophus, Alcaligenes paradoxus, and Paracoccus denitrificans, were transconjugated with pKSEGF2 from eight hydrogen-utilizing bacteria tested. In these transconjugated hydrogen-utilizing bacteria, P. pseudoflava carrying pKSEGF2 grew autotrophically and secreted EGF, confirmed by Western blot (immunoblot) analysis, into the culture medium constitutively.


COEVOLUTION AND AVIAN BROOD PARASITISM: COWBIRD EGGS SHOW EVOLUTIONARY RESPONSE TO HOST DISCRIMINATION.
The Rufous Hornero (Furnarius rufus) is an important host of the brood parasitic Shiny Cowbird (Molothrus bonariensis) in Uruguay, but not in nearby Buenos Aires Province, Argentina. Eggs of the Shiny Cowbird are extremely variable in size, and horneros eject cowbird eggs with widths less than about 88% of the widths of their own eggs. Uruguayan cowbird eggs are, on average, 12% larger than those from Buenos Aires, a geographic pattern in egg size that corresponds to the pattern of successful host use. Uruguayan cowbird eggs are also wider per unit volume than eggs from Buenos Aires. Allometric analyses of egg width and volume indicate that this shape change is apparently an evolutionary response to selection exerted by the hornero. Such a response is absent in Buenos Aires because interactions between the cowbird and the hornero are probably of recent origin there.


Optical response of heterogeneous polymer layers containing silver nanostructures.
This work is focused on the study of the optical properties of silver nanostructures embedded in a polymer host matrix. The introduction of silver nanostructures in polymer thin films is assumed to result in layers having adaptable optical properties. Thin film layers with inclusions of differently shaped nanoparticles, such as nanospheres and nanoprisms, and of different sizes, are optically characterized. The nanoparticles are produced by a simple chemical synthesis at room temperature in water. The plasmonic resonance peaks of the different colloidal solutions range from 390 to 1300 nm. The non-absorbing, transparent polymer matrix poly(vinylpyrrolidone) (PVP) was chosen because of its suitable optical and chemical properties. The optical studies of the layers include spectrophotometry and spectroscopic ellipsometry measurements, which provide information about the reflection, transmission, absorption of the material as well as the complex optical indices, n and k. Finite difference time domain simulations of nanoparticles in thin film layers allow the visualization of the nanoparticle interactions or the electric field enhancement on and around the nanoparticles to complete the optical characterization. A simple analysis method is proposed to obtain the complex refractive index of nanospheres and nanoprisms in a polymer matrix.


Endothelial dysfunction in femoral artery of the hypertensive rats is nitric oxide independent.
This study examined nitric oxide (NO) production, oxidative load and endothelium-dependent relaxation (NO-dependent and NO-independent) in adult male borderline hypertensive (BHR) and spontaneously hypertensive (SHR) rats as compared to normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressure (BP) was determined by tail-cuff. NO production was determined by conversion of [(3)H]-L-arginine. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured for assessment of oxidative load. Vascular function was investigated in rings of the femoral artery (FA) using a wire myograph. BP of WKY, BHR and SHR was 106+/-2, 143+/-3 and 191+/-3 mm Hg, respectively (p<0.01 for each). Significant left ventricle (LV) hypertrophy and elevated levels of CD and TBARS in the LV were present in BHR and SHR as compared to WKY. NO production was elevated significantly in the aorta of BHR and SHR vs. WKY as well as in the LV of SHR vs. WKY. Acetylcholine (ACh)-induced relaxation of the FA was reduced significantly in both BHR and SHR vs. WKY. The NO-dependent component of ACh-induced relaxation had increasing tendency in hypertensive groups and it correlated positively with BP. The NO-independent component of vasorelaxation was reduced significantly in BHR and SHR vs. WKY and it correlated negatively with BP. In conclusion, the results showed that endothelial dysfunction in the experimental model of borderline hypertensive and hypertensive rats is NO-independent. The results suggest that borderline hypertension represents a risk of other cardiovascular disorders which is qualitatively similar to that of fully developed hypertension.


Cobalt-assisted in situ synthesis of crystalline bismuth nanoparticle arrays.
Almost monodisperse, crystalline Bi nanoparticle arrays were synthesized using a newly developed method, magnetically assisted growth of Bi nanoparticles (MAGBINs). The MAGBIN utilizes co-sputtering from Bi and Co targets at an elevated temperature. Crystalline Bi nanoparticles with hexagonal morphology were formed in situ on a Si substrate with a thin surface oxide during this process. The size and density of Bi nanoparticles could be controlled by adjusting the relative powers applied to Bi and Co targets, and they showed opposite trends against the relative powers. Several physical processes such as Co agglomeration, element-selective growth, and Ostwald ripening were proposed to be involved in this Bi nanoparticle growth. The MAGBIN is a facile method to synthesize crystalline Bi nanoparticle arrays, which does not need any chemical agents, complex process, or lithography.


Septic shock due to Fournier's gangrene of the scrotum.
A 57-year-old morbidly obese (160 kg) man presented with a 12 h history of severe bilateral scrotal pain and swelling. His scrotum was erythematous, with cellulitis advancing superiorly along the anterior abdominal wall. He was in septic shock. Following resuscitation with intravenous fluids, commencement of vasopressor infusion and broad-spectrum antimicrobials, he underwent surgical exploration and debridement. This revealed a devitalised gangrenous scrotum with abscess formation noted in the ischio-rectal spaces. This was debrided posteriorly to the wall of the rectum. The penis was de-gloved. Both testicles were spared. A colostomy was performed on day 3 to maintain a clean environment for healing. Subsequent scrotal reconstruction and grafting was performed with a pedicled gracilis flap and split skin grafting. The colostomy was reversed at 5 months.


Structure-efficiency relationship of [1,2,4]triazol-3-ylamines as novel nicotinamide isosteres that inhibit tankyrases.
Tankyrases 1 and 2 are members of the poly(ADP-ribose) polymerase (PARP) family of enzymes that modulate Wnt pathway signaling. While amide- and lactam-based nicotinamide mimetics that inhibit tankyrase activity, such as XAV939, are well-known, herein we report the discovery and evaluation of a novel nicotinamide isostere that demonstrates selectivity over other PARP family members. We demonstrate the utilization of lipophilic efficiency-based structure-efficiency relationships (SER) to rapidly drive the evaluation of this series. These efforts led to a series of selective, cell-active compounds with solubility, physicochemical, and in vitro properties suitable for further optimization.


Isolated myeloid sarcoma of the neck and chest: differential diagnosis and therapeutic approach.
In this article, we present the case of a 57-year-old man with cervical and mediastinal tumor mass, normal blood count as well as virusological status. Cervical tumor tissue biopsy revealed cells positive for CD34, CD13, LCA, CD33, and CD163 but negative for T-cell and B-cell markers, NK-cell markers, plasmacytic markers and anaplastic large cell lymphoma markers. These features were consistent with myeloid sarcoma of the neck with involvement of the mediastinum. We discussed differential diagnosis and therapy of isolated myeloid sarcoma and suggest that clinical presentation, cell morphology, complete immunophenotype, and specific genotypic lesions in some cases, must be evaluated.


Let's face it: patient and parent perspectives on incorporating a Facebook group into a multidisciplinary weight management program.
Social media may have the potential to enhance weight management efforts. However, the acceptability of incorporating this entity into pediatrics is unknown. The objective of this project was to explore patients' and parents' perspectives about developing a Facebook group as a component of a pediatric weight management program. Semistructured interviews were performed between September, 2011, and February, 2012, with patients and parents in a multidisciplinary weight management program. Interviews explored participants' perceptions of potential benefits, concerns, and preferences related to a program-specific Facebook group. Transcripts were reviewed and themes identified. The study concluded when thematic saturation was achieved. Participants (n=32) were largely enthusiastic about the idea of a program-specific Facebook group for adolescents. Most preferred a secret group, where only participants would know of the group's existence or group members' identity. No parents expressed concern about security or privacy related to a program-specific Facebook group; one parent expressed concern about undesirable advertisements. Participants endorsed a variety of ideas for inclusion on the page, including weight loss tips, live chats with providers, quizzes, and an incentive system where participants could gain points for making healthy choices. Many parents requested a separate parent-focused page, an idea that was supported by the adolescents. This study suggests that participants perceive potential benefits from incorporating social media interventions into pediatric weight management efforts. Privacy and security issues do not appear to be major parental concerns. Future work should explore the impact of program-specific social media interventions on outcomes for patients in weight management programs.


Cardiac adaptation to endurance exercise training: Differential impact of swimming and running.
Objectives: High-intensity training has been associated with bi-ventricular and bi-atrial remodelling and a potentially increased risk of arrhythmias. Most of the evidence is based on endurance disciplines mainly involving the lower part of the body, while few data is available on upper body disciplines. The purpose of this study was to compare chronic cardiac remodelling induced by running and swimming as well as the acute response of ventricular and atrial performance after an upper-body and a lower-body endurance race. Methods: Standard and speckle tracking echocardiographic assessment of left ventricle, right ventricle and both atria was performed at baseline and immediately after a 9.5 km open-water swimming race in 26 healthy men and before and after a 35 km-trail-running race in 21 male runners. Results: No significant differences were observed in baseline ventricular dimensions. However, both right ventricular and atrial systolic deformation were greater in runners. This group also showed slightly larger atrial volumes as compared to swimmers. After the race, right ventricular dilatation was observed in both groups, but only runners showed a decrease in right ventricular deformation and a decrease in atrial volumes and deformation. Significant increases in atrial deformation without reduction in atrial volumes were observed only in swimmers after the race. Conclusions: Right ventricular and atrial remodelling is different depending on the endurance training discipline. Long-distance running races induce a greater impairment in right ventricular performance and atrial function compared to endurance swimming competitions.


Marked production of ginsenosides Rd, F2, Rg3, and compound K by enzymatic method.
The hydrolysis of protopanaxadiol-type saponin mixture by various glycoside hydrolases was examined. Among these enzymes, crude preparations of lactase from Aspergillus oryzae, beta-galactosidase from A. oryzae, and cellulase from Trichoderma viride were found to produce ginsenoside F(2) [3-O-(beta-D-glucopyranosyl)-20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], compound K [20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], and ginsenoside Rd {3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol}, respectively, from protopanaxadiol-type saponin mixture in large quantities. Moreover, the crude preparation of lactase from Penicillium sp. having a high producing activity of ginsenoside Rh(1) (6-O-beta-D-glucopyranosyl-20(S)-protopanaxatriol) from protopanaxatriol-type saponin mixture gave ginsenoside Rd as a main product, ginsenoside Rg(3) {3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20(S)-protopanaxadiol}, and compound K from protopanaxadiol-type saponin mixture. The hydrolytic pathways of ginsenosides Rb(1), Rb(2), and Rc to ginsenosides Rd, Rg(3), and F(2), and compound K by crude preparations of four glycoside hydrolases were also studied. This is the first report on the enzymatic preparation of an intestinal bacterial metabolite, ginsenoside F(2), in quantity, and a considerable amount of a minor saponin, ginsenoside Rg(3), from a protopanaxadiol-type saponin mixture.


Similarity search profiling reveals effects of fingerprint scaling in virtual screening.
Fingerprint scaling is a method to increase the performance of similarity search calculations. It is based on the detection of bit patterns in keyed fingerprints that are signatures of specific compound classes. Application of scaling factors to consensus bits that are mostly set on emphasizes signature bit patterns during similarity searching and has been shown to improve search results for different fingerprints. Similarity search profiling has recently been introduced as a method to analyze similarity search calculations. Profiles separately monitor correctly identified hits and other detected database compounds as a function of similarity threshold values and make it possible to estimate whether virtual screening calculations can be successful or to evaluate why they fail. This similarity search profile technique has been applied here to study fingerprint scaling in detail and better understand effects that are responsible for its performance. In particular, we have focused on the qualitative and quantitative analysis of similarity search profiles under scaling conditions. Therefore, we have carried out systematic similarity search calculations for 23 biological activity classes under scaling conditions over a wide range of scaling factors in a compound database containing approximately 1.3 million molecules and monitored these calculations in similarity search profiles. Analysis of these profiles confirmed increases in hit rates as a consequence of scaling and revealed that scaling influences similarity search calculations in different ways. Based on scaled similarity search profiles, compound sets could be divided into different categories. In a number of cases, increases in search performance under scaling conditions were due to a more significant relative increase in correctly identified hits than detected false-positives. This was also consistent with the finding that preferred similarity threshold values increased due to fingerprint scaling, which was well illustrated by similarity search profiling.


Chromo-fluorogenic sensors for chemical warfare agents in real-time analysis: journey towards accurate detection and differentiation.
The existence of chemical weapons (blister and nerve agents) is an unfortunate reality of the modern world. The usage of these chemical agents by rogue states or terrorist groups has showcased their ugly faces in the past and even in recent years. Despite extensive and strenuous efforts by the Organization for the Prohibition of Chemical Weapons (OPCW) to eliminate chemical warfare agents (CWAs) by the prohibition of their production and the destruction of their stockpiles, many countries still possess them in enormous quantities. Given the potential threat from these lethal agents, it is imperative to have a foolproof chemical sensor and detection system, which should consist of readily deployable chemical probes that can operate with high specificity and sensitivity. Over the last decade, our group has been engaged in designing and developing novel field-deployable sensing techniques by exploring approaches based on supramolecular tools, which can result in excellent specificity, sensitivity, high speed, portability and low cost. In this article, I describe our group's journey and success stories in the development of chemical warfare detection protocols, detailing the range of unique chemical probes and methods explored to achieve the specific detection of individual agents under real environmental conditions. It is interesting to note that the combination of three molecular probes (SQ, Fc and LH2) could simply achieve the detection of all CWAs at room temperature in one go without the need for nonportable and expensive instruments. The ease and generality of these techniques/methods suggest great promise for the highly specific chemical sensing of almost the entire class of CWAs. In this paper, a brief introduction is first provided to present the basic chemistry related to CWAs and the importance of supramolecular chemistry in the design of new protocols with new insights. The manipulation of molecular probes is then debated towards the development of a system for the chromo-fluorogenic sensing of CWAs without interference from most relevant analytes. Finally, the outlook of open challenges and the future developments of this rapidly evolving field is discussed.


Preclinical science regarding cannabinoids as analgesics: an overview.
Modern pharmacology of cannabinoids began in 1964 with the isolation and partial synthesis of delta-9-tetrahydrocannabinol, the main psycho-active agent in herbal cannabis. Since then, potent antinociceptive and antihyperalgesic effects of cannabinoid agonists in animal models of acute and chronic pain; the presence of cannabinoid receptors in pain-processing areas of the brain, spinal cord and periphery; and evidence supporting endogenous modulation of pain systems by cannabinoids has provided support that cannabinoids exhibit significant potential as analgesics. The present article presents an overview of the preclinical science.


Congenital heart disease beyond the age of 60: emergence of a new population with high resource utilization, high morbidity, and high mortality.
The population of adults with congenital heart disease (ACHD) is growing and ageing. Limited information about the diagnostic spectrum of this emerging population, its resource utilization at tertiary ACHD centres, and especially about prognostic parameters is available. Retrospective cohort study on all ACHD patients ≥60 years of age under active follow-up. All-cause mortality was the primary outcome measure. Out of a total population of 7315 ACHD patients, 375 [190 females (50.7%), mean age 64.8 ± 5.9 years] fulfilled the inclusion criteria. During a median follow-up of 5.5 (IQR 3.1-8.6) years, 55 of the 375 patients died. The number of interventions (P = 0.0006), the number and length of hospitalization (P < 0.0001), and the number of outpatient clinic visits (P < 0.0001) were significantly higher in patients ≥60 compared with patients aged between 20 and 60 years. Patients ≥60 years of age with moderate or severe congenital heart defects had worse survival prospects than their age- and gender-matched comparison population. On multivariate Cox analysis, coronary artery disease [hazard ratio (HR): 5.04; 95%CI: 1.88-13.51, P = 0.0014], symptoms of heart failure (HR: 2.36; 95%CI: 1.05-5.29, P < 0.05), NYHA class (HR: 1.96; 95%CI: 1.18-3.26, P < 0.01), and moderate to severe reduction in systemic ventricular systolic function (HR: 1.90; 95%CI: 1.20-2.99, P < 0.001) were the strongest prognostic factors. There is a growing number of elderly ACHD patients with high mortality rates and a higher utilization of healthcare resources compared with younger patients. Acquired morbidities, such as coronary artery disease, seem to be key determinants of outcome in this older population in conjunction with the underlying congenital heart disease.


Homogenization and Equivalent Beam Model for Fiber-Reinforced Tubular Profiles.
The current work presents a study on hollow cylinder composite beams, since hollow cylinder cross-sections are one of the principal geometry in many engineering fields. In particular, the present study considers the use of these profiles for scaffold design in offshore engineering. Composite beams cannot be treated as isotropic ones due to couplings mainly present among traction, torsion, bending and shear coefficients. This research aims to present a simple approach to study composite beams as they behave like isotropic ones by removing most complexities related to composite material design (e.g., avoid the use of 2D and 3D finite element modeling). The work aims to obtain the stiffness matrix of the equivalent beam through an analytical approach which is valid for most of the laminated composite configurations present in engineering applications. The 3D Euler-Bernoulli beam theory is considered for obtaining the correspondent isotropic elastic coefficients. The outcomes show that negligible errors occur for some equivalent composite configurations by allowing designers to continue using commercial finite element codes that implement the classical isotropic beam model.


Climate change is predicted to alter the current pest status of Globodera pallida and G. rostochiensis in the United Kingdom.
The potato cyst nematodes Globodera pallida and G. rostochiensis are economically important plant pathogens causing losses to UK potato harvests estimated at £50 m/ year. Implications of climate change on their future pest status have not been fully considered. Here, we report growth of female G. pallida and G. rostochiensis over the range 15 to 25°C. Females per plant and their fecundity declined progressively with temperatures above 17.5°C for G. pallida, whilst females per plant were optimal between 17.5 and 22.5°C for G. rostochiensis. Relative reproductive success with temperature was confirmed on two potato cultivars infected with either species at 15, 22.5 and 25°C. The reduced reproductive success of G. pallida at 22.5°C relative to 15°C was also recorded for a further seven host cultivars studied. The differences in optimal temperatures for reproductive success may relate to known differences in the altitude of their regions of origin in the Andes. Exposure of G. pallida to a diurnal temperature stress for one week during female growth significantly suppressed subsequent growth for one week at 17.5°C but had no effect on G. rostochiensis. However, after two weeks of recovery, female size was not significantly different from that for the control treatment. Future soil temperatures were simulated for medium- and high-emission scenarios and combined with nematode growth data to project future implications of climate change for the two species. Increased soil temperatures associated with climate change may reduce the pest status of G. pallida but benefit G. rostochiensis especially in the southern United Kingdom. We conclude that plant breeders may be able to exploit the thermal limits of G. pallida by developing potato cultivars able to grow under future warm summer conditions. Existing widely deployed resistance to G. rostochiensis is an important characteristic to retain for new potato cultivars.


Children in the hospital: issues of power and vulnerability.
Findings from a phenomenological study into the experience of pediatric nurses highlight the unequal power relationships between children and adults, including parents and health care providers. Based on the principle of 'in the child's best interest' this thinking has the potential to deny children an age appropriate right to be involved in health care decisions and may conflict with the tenets of the United Nations Convention on the Rights of the Child. Adults are presumed competent to make health care decisions, children are presumed incompetent without any validation as to whether the child has the knowledge and ability to make the decision. Consent does not only apply to major procedures, but to all patient care activities. The right of access to children's bodies is always in the hands of others and some everyday practices may conflict with protective behavior education.


Weekly doxorubicin increases coronary arteriolar wall and adventitial thickness.
Doxorubicin (DOX) is associated with premature cardiovascular events including myocardial infarction. This study was performed to determine if the weekly administration of DOX influenced coronary arteriolar medial and/or adventitial wall thickening. Thirty-two male Sprague-Dawley rats aged 25.1± 2.4 weeks were randomly divided into three groups and received weekly intraperitoneal injections of normal saline (saline, n = 7), or low (1.5 mg/kg to 1.75 mg/kg, n = 14) or high (2.5 mg/kg, n = 11) doses of DOX. The animals were treated for 2-12 weeks, and euthanized at pre-specified intervals (2, 4, 7, or 10+ weeks) to obtain histopathologic assessments of coronary arteriolar lumen diameter, medial wall thickness, adventitial wall thickness, and total wall thickness (medial thickness + adventitial thickness). Lumen diameter was similar across all groups (saline: 315±34 µm, low DOX: 286±24 µm, high DOX: 242±27 µm; p = 0.22). In comparison to animals receiving weekly saline, animals receiving weekly injections of 2.5 mg/kg of DOX experienced an increase in medial (23±2 µm vs. 13±3 µm; p = 0.005), and total wall thickness (51±4 µm vs. 36±5 µm; p = 0.022), respectively. These increases, as well as adventitial thickening became more prominent after normalizing for lumen diameter (p<0.05 to p<0.001) and after adjusting for age, weight, and total cumulative DOX dose (p = 0.02 to p = 0.01). Animals receiving low dose DOX trended toward increases in adventitial and total wall thickness after normalization to lumen diameter and accounting for age, weight, and total cumulative DOX dose (p = 0.06 and 0.09, respectively). In conclusion, these data demonstrate that weekly treatment of rats with higher doses of DOX increases coronary arteriolar medial, adventitial, and total wall thickness. Future studies are warranted to determine if DOX related coronary arteriolar effects are reversible or preventable, exacerbate the known cardiomyopathic effects of DOX, influence altered resting or stress-induced myocardial perfusion, or contribute to the occurrence of myocardial infarction.


Changes in physical properties of ovarian membranes after hCG-induced desensitization in rats.
Using pseudopregnant rat ovaries, the possibility was examined whether hCG-induced early desensitization of the LH/hCG receptor was accompanied by changes in the physical state of membranes. Thirty min after a single s.c. injection of 75 IU hCG, the hCG-responsive adenylylcyclase activity was reduced, whereas hCG binding to ovarian membranes was still normal. Membrane lipid rigidity, as determined by fluorescence polarization of DPH, decreased as early as 30 min after injection of a desensitizing dose of hCG. There was no difference in membrane rigidity when ovarian membranes were incubated 0.5 or 2 h with hCG or LH. The decrease of membrane lipid rigidity in the process of rapid desensitization of rat luteal tissue does not appear to be associated with protein synthesis. Desensitization also modified the differential scanning calorimetric profile. The results indicate that hCG-induced changes in the physical state of rat ovary membranes are preceded by the process of desensitization.


Viral-mediated gene transfer for cancer treatment.
Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses that retain the capability of the virus for efficient gene delivery but are safer than the native virus due to modifications that eliminate or alter one or more essential viral functions. The field of viral-based gene transfer vectors for the treatment of cancer has now entered the final stage of clinical testing prior to possible product approvals. Three viral vectors are currently undergoing this Phase III or Phase II/III clinical testing for cancer treatment. All three of these vectors are based on adenovirus, a common human virus that in its native state can cause cold or flu-like symptoms. In two of these vectors, genes essential for viral replication have been replaced with the wild-type p53 tumor suppressor gene, a gene that is deleted or mutated in over 50% of human cancers and which, when transferred into tumor cells, can induce tumor cell death. The third vector retains more of the natural adenoviral functions and relies on replication in tumor cells to induce cell killing. These three vectors represent two of the approaches now being taken to develop viral-based gene transfer vectors for cancer treatment. Additional approaches include the transfer of genes capable of converting non-toxic prodrugs into toxic forms, using anti-angiogenic gene transfer to block the formation of tumor blood vessels, inhibiting the activity of oncogenes through blocks to transcription or translation, stimulating the body's own immune system with immunomodulatory genes, and "cancer vaccination" with genes for tumor antigens. The data derived to date from clinical trials with viral-based vector systems are promising. The vectors have been generally well-tolerated without the severe toxicities common to standard cancer treatments. Many of these vectors have been demonstrated to have anti-tumor activity in a clinical setting and to lead to tumor regressions or to reductions in the rate of tumor growth. Furthermore, the safety profile of these vector systems has allowed for their clinical testing in combination with conventional cancer treatments to determine their benefit in multi-modality therapy. As part of their clinical development, all three of the vectors in Phase III and Phase II/III clinical trials are being tested for their benefit in combination with chemotherapy in randomized trials. The field is also looking to future product opportunities with improvements that will further increase potency, safety, and/or ease of administration. These developments may expand the number of cells that are susceptible to infection or may target the vector to particular tumor types following an intravenous administration. Some of these approaches are already in clinical testing. Additional opportunities may utilize multigene strategies to target multiple pathways in cancer cells or expand the use of cytotoxic or cytostatic gene transfer in combination with immunotherapy.


Epilepsy Surgery in Hospital Universiti Sains Malaysia: Our Experiences since 2004.
Epilepsy surgery has been performed by a few centres in Malaysia, including Hospital Universiti Sains Malaysia (HUSM). To date, a total of 15 patients have undergone epilepsy surgery in HUSM. The epilepsy surgery included anterior temporal lobectomy (ATL) with amygdalohippocampectomy (AH) and Vagal nerve stimulation (VNS). The surgical outcomes of the patients were assessed using the International League Against Epilepsy (ILAE) outcome scale. The ILAE scores for patients who underwent ATL with AH were comparatively better than those who underwent VNS. One of the patient who underwent ATL with AH and frontal lesionectomy was found to have psychosis during follow up. Epilepsy surgery has proven to be an important treatment for medically resistant epilepsy. Thus it is important to raise public awareness regarding epilepsy and its treatment.


Anti-obesity effects of yellow catfish protein hydrolysate on mice fed a 45% kcal high-fat diet.
Obesity contributes to the etiologies of a variety of comorbid conditions, such as type 2 diabetes, hypertension and cardiovascular disease. In the present study, the anti-obesity effects of yellow catfish protein hydrolysate (YPh) were observed in mice fed a 45% kcal high-fat diet (HFD) compared with those of mice treated with simvastatin. The HFD-fed control mice exhibited noticeable increase in body weight, and whole-body and abdominal fat densities, periovarian and abdominal wall-deposited fat pad weight, as well as in the levels of triglycerides (TG), blood total cholesterol (TC), low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase, creatinine, blood urea nitrogen, and in the fecal TG and TC contents. However, they exhibited a decrease in serum high-density lipoprotein levels. In addition, an increase was detected in periovarian and dorsal abdominally deposited fat pad thickness, adipocyte hypertrophy, the number of steatohepatitis regions, hepatocyte hypertrophy and lipid droplet deposition-related renal tubular vacuolation degenerative lesions, along with increased hepatic lipid peroxidation and a deteriorated endogenous antioxidant defense system (glutathione, catalase and superoxide dismutase). However, all the above-mentioned obesity-related complications were dose-dependently and significantly inhibited after 84 days of thye consecutive oral administration of 125, 250 and 500 mg/kg YPh. In addition, YPh dose-dependently depleted the liver endogenous antioxidant defense system and inhibited hepatic lipid peroxidation. Overall, the effects of 250 mg/kg YPh on HFD-induced obesity and related complications were similar or more potent than those of 10 mg/kg simvastatin. These results indicate that YPh is a promising new potent medicinal ingredient for possible use in the treatment of obesity and related complications.


[Smarter Medicine in Headache Care - presentation and discussion of 5 recommendations].
Smarter Medicine in Headache Care - presentation and discussion of 5 recommendations Abstract. An unequivocal headache diagnosis cannot always be made. The lack of diagnostic tests able to prove primary headaches often prompts physicians to perform unnecessary examinations to reduce their uncertainty. When setting out the therapeutic strategy, again, insecurity often leads to mendable choices. In this Delphi study, members of the therapy commission of the Swiss Headache Society collected, rated, and re-rated doubtful and questionable procedures. Five recommendations that resulted from this survey are presented and reviewed in this article. The recommendations are: (A) no repeated cerebral imaging in headaches with unchanged phenotype; (B) no computed tomography in the work-up of non-acute headaches; (C) no tooth extraction to treat persistent idiopathic facial pain, (D) no migraine surgery; (E) no removal of amalgam fillings to treat headache disorders.


Association between NF-κB Signal Pathway-Related Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density.
Osteoporosis is a systemic bone disease characterized by reduction of bone content. Bisphosphonates are first-line treatments for osteoporosis, but they have variable effectiveness. Genetic factors may explain these differences. The NF-κB signaling pathway plays a key role in the regulation of bone metabolism. We aimed to determine whether genetic variations in the NF-κB signaling pathway affect the effectiveness of alendronate in postmenopausal Chinese women with low bone mass. We recruited 455 postmenopausal Han Chinese women with primary osteoporosis or osteopenia aged 48-90 yrs who had experienced no spontaneous menses for at least 1 yr. All participants had dual X-ray absorptiometry (DEXA) bone mineral density (BMD) measurement at baseline and 1 yr after treatment. Treatment involved 1 yr administration of 70 mg oral alendronate weekly and 600 mg calcium and 125 IU of vitamin D daily. Thirteen tagSNPs in NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068), RELA (rs7119750, rs11820062), and NLRC5 (rs289747, rs1566439, rs1684575, rs289726, rs289723, and rs41383) were chosen from the NCBI Locus Link and HapMap and genotyped individually. Genetic variation in these genes and the corresponding therapeutic response to alendronate treatment were analyzed. Among the 13 tagSNPs, rs289747 was significantly correlated with the BMD change rate at the femoral neck (P=0.048). This significance no longer existed after Bonferroni correction. We then performed principal component analysis (PCA) and found NLRC5 (rs289747 and rs1566439) were strongly correlated with alendronate efficacy in femoral phenotypes and were major components of BMD change values, particularly total hip and intertrochanteric phenotypes. Furthermore, the PLINK linear regression GLM model revealed that haplotype TT of RELA (rs7119750 and rs11820062) and ICCTA of NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068) were associated with BMD of the total hip among each haplotype after 1 yr of treatment. The NF-κB1, RELA, and NLRC5 genetic variations affect the therapeutic response of alendronate treatment for postmenopausal osteoporosis.


Evaluation of the Functional Treatment of Patients With Skeletal Class II Malocclusion Using Low-Level Laser Therapy-Assisted Twin-Block Appliance: A Three-Arm Randomized Controlled Trial.
Background Different techniques have been used to reduce functional treatment time including low-level laser therapy (LLLT), and the majority of studies have been conducted on animals. Therefore, the aim of the current study was to evaluate the effects of LLLT on improving orthodontic functional treatment using the Twin-Block (TB) appliance. Materials and methods This study was a three-arm, parallel-group randomized controlled trial. Patients were selected using the following inclusion criteria: skeletal Class II Division 1 malocclusion resulting from mandibular retrognathia (angle between the anterior cranial base and the NB plane (i.e., SNB angle): 73°-78°), the sagittal skeletal discrepancy angle (ANB angle) between 4° and 9°, and overjet between 5 and 9 mm. Forty-eight patients were randomly allocated into three equal groups. In the LLLT-TB group, the low-level laser device was used with a wavelength of 808 nm and power of 250 mW in addition to functional treatment with a Twin-Block appliance. The laser was applied on the skin at the bilateral temporomandibular joint (TMJ) regions, at five points, each point received 5 J of the laser for 20 seconds. The laser course was twice a week in the first month, every two weeks in the second month, and every three weeks up to the end of the treatment. The second group (the TB group) received functional treatment with a Twin-Block appliance, while patients in the third group (the untreated control group (UCG)) were observed for nine months without any intervention. Results There were statistically significant differences in treatment periods between the LLLT-TB group and the TB group (129 days and 235 days, respectively, P-value<0.001). The change in the effective mandibular length (Co-Gn) was the highest in the LLLT-TB group compared with the TB and the UCG groups (4.41 mm, 3.66 mm, and 1.07 mm, respectively; P-value<0.001). Conclusions The application of low-level laser therapy on the condylar regions accelerated the functional treatment in skeletal Class II malocclusion patients by approximately 45% and increased the bone growth and mandibular length. The improvement in the SNB angle was similar in both interventional groups. Irradiation of low-level laser stimulated bone growth at the condyles and did not cause anterior movement of the temporomandibular joint following functional orthopedic correction.


The comparative study of reactive oxygen species generated by polymorphonuclear leukocytes as alpha 1-proteinase inhibitor inactivators-possible application for antioxidant prevention of emphysema.
The oxidative inactivation of alpha 1-proteinase (alpha 1AP) inhibitor is a one of mechanisms that may lead to the pulmonary emphysema. This process is caused by oxidants derived from atmosphere and released from lung phagocytes. These cells produce various oxidants hydrogen peroxide (H2O2), hypochlorous acid (HClO), hydroxyl (OH.) and superoxide (O2-) radicals after inflammatory stimulation. In this study I have investigated the effects of H2O2 (1.5 x 10(-5) to 1.5 x 10(-2) M) alone or with addition of FeCl2 (50 microM) in order to generate OH., chloramine-T (1.5 x 10(-5) to 1.5 x 10(-3) M) which generates HClO, glucose 10 mg/ml-glucose oxidase (12.5 to 80 mU/ml)-H2O2 generating system, xanthine 0.2 mM-xanthine oxidase (12.5 to 80 mU/ml)-O2-2 generating system on the elastase inhibitory activity of alpha 1AP in vitro. H2O2 was weak in alpha 1AP inactivation--only concentration of H2O2 1.5 x 10(-2) caused severe loss of its activity to 23 +/- 8% inhibition of elastase. Addition of FeCl2 to H2O2 and following OH. generation did not enhance its alpha 1AP inactivation. O2-2 generating system inhibited moderately alpha 1AP. The % inhibition of elastase at concentration of xanthine oxidase 80 mU/ml was 65 +/- 7. HClO was most effective as an alpha 1AP inactivator. All used chloramine-T concentrations completely suppressed alpha 1AP activity. The obtained results and in vivo consumption of H2O2 by polymorphonuclear leukocyte myeloperoxidase for HClO production suggest that scavenging of these reactive oxygen species may be useful in prevention of emphysema.


Coicenals A-D, four new diterpenoids with new chemical skeletons from the plant pathogenic fungus Bipolaris coicis.
Coicenals A-C (1-3) possessing a previously undescribed 10-(sec-butyl)-6-hydroxy-1,7,9-trimethyl-1,6,7,8,9,9a-hexahydro-1,4-methanobenzo[d]oxepin-2(4H)-ylidene)acetaldehyde skeleton and coicenal D (4) with a new 2-(sec-butyl)-5-hydroxy-1,6,8-trimethyl-2,5,6,7,8,8a-hexahydro-1H-4a,1-(epoxymethano)naphthalen-10-ylidene)acetaldehyde skeleton were isolated from the solid culture of the plant pathogenic fungus Bipolaris coicis. The absolute configurations in 1 and 4 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1 and 2 were transformed into 4 and 5 by treatment with acetyl chloride, respectively. Compounds 1-4 showed moderate inhibitory activity against NO release with IC50 values of 16.34 ± 1.12, 23.55 ± 1.37, 10.82 ± 0.83, and 54.20 ± 2.82 μM, respectively.


Synthetic peptide octarphin (TPLVTLFK), a selective agonist of nonopioid β-endorphin receptor, stimulates nitric oxide synthesis in macrophages.
Synthetic peptide octarphin (TPLVTLFK, a selective agonist of nonopioid β-endorphin receptor) was able to activate in a dose-dependent manner murine macrophages to express nitric oxide (NO) synthase and to produce NO. Octarphin required lipopolysacharide for the optimal induction of NO production. Octarphin-dependent NO production was sensitive to inhibition by dexamethasone and the NO synthase specific inhibitor NG-monomethyl-L-arginine. In the concentration range of 1-1000 nM, octarphin increased the cyclic 3',5'-guanosine monophosphate (cGMP) content in macrophages stimulated with lipopolysacharide. The effect was dependent on the peptide concentration and was maximal at a concentration of 100 nM. Thus, octarphin stimulates both NO and cGMP production in macrophages.


Stimuli-responsive biomaterials: smart avenue toward 4D bioprinting.
3D bioprinting is an advanced technology combining cells and bioactive molecules within a single bioscaffold; however, this scaffold cannot change, modify or grow in response to a dynamic implemented environment. Lately, a new era of smart polymers and hydrogels has emerged, which can add another dimension, e.g., time to 3D bioprinting, to address some of the current approaches' limitations. This concept is indicated as 4D bioprinting. This approach may assist in fabricating tissue-like structures with a configuration and function that mimic the natural tissue. These scaffolds can change and reform as the tissue are transformed with the potential of specific drug or biomolecules released for various biomedical applications, such as biosensing, wound healing, soft robotics, drug delivery, and tissue engineering, though 4D bioprinting is still in its early stages and more works are required to advance it. In this review article, the critical challenge in the field of 4D bioprinting and transformations from 3D bioprinting to 4D phases is reviewed. Also, the mechanistic aspects from the chemistry and material science point of view are discussed too.


Research Advances on the Bioactivity of 1,2,3-Triazolium Salts.
1,2,3-Triazolium salts have demonstrated significant potential in the fields of medicine and agriculture, exhibiting exceptional antibacterial, antifungal, anticancer, and antileishmanial properties. Moreover, these salts can be utilized as additives or components to produce nano- and fiber-based materials with antibacterial properties. In this review, we summarize several synthetic strategies to obtain 1,2,3-triazolium salts and the structures of 1,2,3-triazolium derivatives with biological activities in the domains of pharmaceuticals, pesticides, and functional materials. Additionally, the structure-activity relationship (SAR) of 1,2,3-triazolium salts with different biological activities has been analyzed. Finally, this review presents the potential applications and prospects of 1,2,3-triazolium salts in the fields of agriculture, medicine, and industrial synthesis.


In vitro effect of synthetic pyocyanine on neutrophil superoxide production.
Pyocyanine, a low-molecular-weight phenazine pigment produced by Pseudomonas aeruginosa, has previously been shown to strongly inhibit human lymphocyte blastogenesis. We now report that synthetic pyocyanine can also affect the generation of superoxide by human peripheral blood polymorphonuclear leukocytes (PMNs) in a dose-dependent manner. Superoxide production by PMNs stimulated with phorbol myristate acetate (PMA) was measured in the presence and absence of pyocyanine, phenazine, and trifluoperazine, a phenothiazine of similar chemical structure to the phenazine pigments. Pyocyanine at 50 microM inhibited superoxide production to 28.9 +/- 2.8% of PMA control values, whereas at the lower concentration of 1 microM, the production of superoxide was significantly enhanced (203 +/- 31.7% of PMA control values). Phenazine, the tricyclic parent compound of pyocyanine, had only a minor effect. Trifluoperazine had a marked inhibitory effect on superoxide generation at concentrations above 1 microM. None of the compounds induced superoxide generation in the absence of PMA. Pyocyanine at all concentrations, unlike phenothiazines, had very little effect on the release of neutrophil granule enzymes. The effect of P. aeruginosa phenazine pigments on polymorphonuclear phagocytes is of significance, since inhibition of host PMN function at sites of infection could result in ineffective bacterial killing, whereas enhanced PMN function could lead to greater tissue damage. These two possibilities are not mutually exclusive and may coexist depending on local pyocyanine concentrations.


Computed tomography in temporal lobe epilepsy.
Forty patients who had intractable temporal lobe epilepsy had surgery for treatment of their seizures following study by computed tomography (CT). Fifteen of 19 patients with tumors had good correlation between CT and pathological findings. Another group of patients had macroscopic changes that were demonstrated on CT and verified at surgery. Sixteen patients had microscopic pathological diagnoses including cytoarchitectural abnormalities, Chaslin gliosis, and ectopic neurons. Six of these had enlarged temporal horns on the ipsilateral and five on the contralateral side to the electroencephalographic-pathological abnormality. In the investigation of temporal lobe epilepsy we believe that CT, especially with the newer generation scanners, records tumors and other larger macroscopic changes but that temporal horn size is unreliable in predicting the abnormal side if only microscopic changes are present.


Aortic Intimal Lipid.
Lipid accumulating in the aortic intima can be considered to be of two origins: from synthesis in situ as found in the cells of the jatty streak, and from serum lipoproteins as found in proximity to elastic and collagen fibers.


[The Dutch National Colesterol Test: participants mainly healthy].
To determine, in people who participated in the Netherlands Heart Foundation's National Cholesterol Test in supermarkets, risk factors for cardiovascular disease and expectations concerning the test result using a questionnaire, and to compare their cholesterol levels with reference values. Descriptive study and questionnaire survey. Participants who underwent the National Cholesterol Test in 9 supermarkets during the summer of 2007 were invited to complete a short questionnaire about risk factors for cardiovascular disease and expectations concerning the test result. Statements about the intention to change behaviour were offered, and the measured total cholesterol level was recorded. The average age of the 684 respondents was 57 years (SD: 16); 72% were female. Participants had on average a lower risk of cardiovascular disease than the general population; they suffered less frequently from diabetes, hypertension and being overweight, and smoked less. The measured cholesterol level was 5.0-6.5 mmol/l in 37% and > 6.5 mmoll in 11%. Elevated cholesterol levels were less common in this group than in the general population. The intention to change behaviour was substantial. The results of this study showed that the National Cholesterol Test reached relatively many healthy, somewhat worried people. The intention to change behaviour was substantial.


[Detection of platelet fibronectin from congenital fibrinogenopenic patients and its clinical significance].
To assess the platelet and plasma concentrations of fibronectin (Fn) and fibrinogen (Fg) in congenital fibrinogenopenic (FgP) patients and explore their role in inducing platelet adhesion and aggregation. A FgP family was selected as study group and the platelets isolated and purified to assess concentrations of Fn and Fg in platelets, alpha-granules and plasma with Western blotting, immuofluoresence staining and flow cytometry (FACS), respectively, the expression of platelets GP II b/III a by FACS. The concentration of platelets Fn in FgP patients is higher than that in controls, and is higher in homozygote than in heterozygote. In contrast, plasma Fn levels were identical in all samples. The amount of platelet Fg from FgP patients is lower than that from the controls and positively correlated with the concentration of their plasma Fg. No difference in the expression of platelet GP II b/III a had been found. It suggested that increased platelet Fn could partially compensate the lack of Fg and lead the platelet adhesion and aggregation.


Multiple infections caused by white spot syndrome virus and Enterocytozoon hepatopenaei in pond-reared Penaeus vannamei in India and multiplex PCR for their simultaneous detection.
White leg shrimp, Penaeus vannamei, were collected on a monthly basis from grow-out ponds located at Tamil Nadu and Andhra Pradesh states along the east coast of India for screening of viral and other pathogens. Totally 240 shrimp samples randomly collected from 92 farms were screened for white spot syndrome virus (WSSV), infectious hypodermal and haematopoietic necrosis virus (IHHNV), infectious myonecrosis virus (IMNV) and Enterocytozoon hepatopenaei (EHP). The number of shrimp collected from shrimp farms ranged from 6 to 20 based on the body weight of the shrimp. All the shrimp collected from one farm were pooled together for screening for pathogens by PCR assay. Among the samples screened, 28 samples were WSSV-positive, one positive for IHHNV and 30 samples positive for EHP. Among the positive samples, four samples were found to be positive for both WSSV and EHP, which indicated that the shrimp had multiple infections with WSSV and EHP. This is the first report on the occurrence of multiple infections caused by WSSV and EHP. Multiplex PCR (m-PCR) protocol was standardized to detect both pathogens simultaneously in single reaction instead of carrying out separate PCR for both pathogens. Using m-PCR assay, naturally infected shrimp samples collected from field showed two prominent bands of 615 and 510 bp for WSSV and EHP, respectively.


Radial tunnel syndrome in psoriatic enthesitis: Complication or coincidence?
Radial tunnel syndrome (RTS) is a rare condition resulting from posterior interosseous nerve (a branch of radial nerve) compression, within the radial tunnel. Lateral epicondylitis as a possible aetiology for RTS has been previously described. Here we report a 64-year-old female, with history of scalp psoriasis, who presented with pain over the lateral aspect of the left elbow and proximal forearm for one year, and decreased sensation over the lateral aspect of distal left forearm including the hand for 20 days. Examination revealed enthesitis at left lateral epicondyle, which was confirmed on magnetic resonance imaging. Touch and pain sensations were reduced over the left thumb, index finger, lateral aspect of the hand and distal forearm, and forearm pain was exaggerated with restricted extension of the wrist and third finger. Rheumatoid factor, anti-nuclear and anti-neutrophil cytoplasmic antibody were negative, and nerve conduction study were normal. A diagnosis of RTS as a possible complication of psoriatic enthesitis was suggested, and patient showed good response to non-steroidal anti-inflammatory drugs.


Life stress and hypertension.
Based on psycho-physiological, clinical and epidemiological studies, essential arterial hypertension is considered to be a consequence of an inadequate 'person-environment fit', objectively, subjectively or both. Besides genetic predisposition, salt intake, obesity and physical inactivity, psychological factors--among them 'hyper-reactivity' of the sympathetic nervous system, predisposing behaviour patterns and stressful life-events--should be taken into account in reaching a better understanding of the causes, prediction and prevention of hypertension. It was demonstrated that a maladaptation in various functional systems, even to minor psycho-emotional stress, is an important pathogenetic link between environment, objectively defined stressors and blood pressure regulation from the earliest phases of the disease. Implications for further research and behavioural interventions, together with other lifestyle-related factors, are discussed for improving the population-based health care in cardiovascular disease in the G.D.R.


The importance of hydraulic architecture to the distribution patterns of trees in a central Amazonian forest.
Species distributions and assemblage composition may be the result of trait selection through environmental filters. Here, we ask whether filtering of species at the local scale could be attributed to their hydraulic architectural traits, revealing the basis of hydrological microhabitat partitioning in a Central Amazonian forest. We analyzed the hydraulic characteristics at tissue (anatomical traits, wood specific gravity (WSG)), organ (leaf area, specific leaf area (SLA), leaf area : sapwood area ratio) and whole-plant (height) levels for 28 pairs of congeneric species from 14 genera restricted to either valleys or plateaus of a terra-firme forest in Central Amazonia. On plateaus, species had higher WSG, but lower mean vessel area, mean vessel hydraulic diameter, sapwood area and SLA than in valleys; traits commonly associated with hydraulic safety. Mean vessel hydraulic diameter and mean vessel area increased with height for both habitats, but leaf area and leaf area : sapwood area ratio investments with tree height declined in valley vs plateau species. [Correction added after online publication 29 March 2017: the preceding sentence has been reworded.] Two strategies for either efficiency or safety were detected, based on vessel size or allocation to sapwood. In conclusion, contrasting hydrological conditions act as environmental filters, generating differences in species composition at the local scale. This has important implications for the prediction of species distributions under future climate change scenarios.


Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis.
Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions.


[Gene therapy and benefits in modulating of system beta-adrenergic in cardiac insufficiency].
Understanding the basic molecular mechanisms that lead to heart failure may allow to define new targets for myocardial gene therapy. In this way, the alterations of the beta-adrenergic signaling that are typically observed in cardiac insufficiency, may be positively modulated by gene manipulation. Both the level and activity of the beta-adrenergic receptor kinase (beta ARK1), a regulatory enzyme that phosphorylates agonist occupied beta-adrenoreceptors, are elevated and account for desensitization of cardiomyocytes to catecholamines. We recently demonstrated that expressing beta ARKct, a peptide which inhibits beta ARK1, allows normalization of contractile function in several animal models of heart failure. This approach may represent a valuable alternative for the treatment of heart failure. The current review summarizes recent studies performed using beta ARKct as a transgene to restore normal beta-adrenergic signaling and improve myocardial function.


Severe destructive nasopharyngeal granulomatosis with polyangiitis with superimposed skull base Pseudomonas aeruginosa osteomyelitis.
Skull base osteomyelitis in the setting of granulomatosis with polyangiitis (GPA) is rare and entails significant diagnostic challenges. We present a case of a 65-year-old Caucasian man with a history of rheumatoid arthritis, off immunosuppression for 18 months, who presented with 2 years of chronic headaches, severe fatigue, saddle nose deformity and 20-kilogram unintentional weight loss. Maxillofacial CT revealed an extensive destructive sinonasal and erosive skull base process. Laboratory evaluation showed equivocal elevation of antiproteinase 3 antibodies with negative antineutrophil cytoplasmic antibody panel. Biopsy of the skull base/clivus revealed necrotising granulomatous inflammation with focal vasculitis consistent with GPA, and multiple bone cultures were positive for Pseudomonas aeruginosa This patient was diagnosed concurrently with GPA and P. aeruginosa skull base osteomyelitis. He was started on a 6-week course of cefepime intravenously and oral prednisone, with the plan to initiate rituximab infusion 2 weeks after initiation of antibiotic therapy.


The disposition index: from individual to population approach.
To correctly evaluate the glucose control system, it is crucial to account for both insulin sensitivity and secretion. The disposition index (DI) is the most widely accepted method to do so. The original paradigm (hyperbolic law) consists of the multiplicative product of indices related to insulin sensitivity and secretion, but more recently, an alternative formula has been proposed with the exponent α (power function law). Traditionally, curve-fitting approaches have been used to evaluate the DI in a population: the algorithmic implementations often introduce some critical issues, such as the assumption that one of the two indices is error free or the effects of the log transformation on the measurement errors. In this work, we review the commonly used approaches and show that they provide biased estimates. Then we propose a novel nonlinear total least square (NLTLS) approach, which does not need to use the approximations built in the previously proposed alternatives, and show its superiority. All of the traditional fit procedures, including NLTLS, account only for uncertainty affecting insulin sensitivity and secretion indices when they are estimated from noisy data. Thus, they fail when part of the observed variability is due to inherent differences in DI values between individuals. To handle this inevitable source of variability, we propose a nonlinear mixed-effects approach that describes the DI using population hyperparameters such as the population typical values and covariance matrix. On simulated data, this novel technique is much more reliable than the curve-fitting approaches, and it proves robust even when no or small population variability is present in the DI values. Applying this new approach to the analysis of real IVGTT data suggests a value of α significantly smaller than 1, supporting the importance of testing the power function law as an alternative to the simpler hyperbolic law.


Digital Biomarker-Based Studies: Scoping Review of Systematic Reviews.
Sensors and digital devices have revolutionized the measurement, collection, and storage of behavioral and physiological data, leading to the new term digital biomarkers. This study aimed to investigate the scope of clinical evidence covered by systematic reviews (SRs) of randomized controlled trials involving digital biomarkers. This scoping review was organized using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. With the search limited to English publications, full-text SRs of digital biomarkers included randomized controlled trials that involved a human population and reported changes in participants' health status. PubMed and the Cochrane Library were searched with time frames limited to 2019 and 2020. The World Health Organization's classification systems for diseases (International Classification of Diseases, Eleventh Revision), health interventions (International Classification of Health Interventions), and bodily functions (International Classification of Functioning, Disability, and Health [ICF]) were used to classify populations, interventions, and outcomes, respectively. A total of 31 SRs met the inclusion criteria. The majority of SRs studied patients with circulatory system diseases (19/31, 61%) and respiratory system diseases (9/31, 29%). Most of the prevalent interventions focused on physical activity behavior (16/31, 52%) and conversion of cardiac rhythm (4/31, 13%). Looking after one's health (physical activity; 15/31, 48%), walking (12/31, 39%), heart rhythm functions (8/31, 26%), and mortality (7/31, 23%) were the most commonly reported outcomes. In total, 16 physiological and behavioral data groups were identified using the ICF tool, such as looking after one's health (physical activity; 14/31, 45%), walking (11/31, 36%), heart rhythm (7/31, 23%), and weight maintenance functions (7/31, 23%). Various digital devices were also studied to collect these data in the included reviews, such as smart glasses, smartwatches, smart bracelets, smart shoes, and smart socks for measuring heart functions, gait pattern functions, and temperature. A substantial number (24/31, 77%) of digital biomarkers were used as interventions. Moreover, wearables (22/31, 71%) were the most common types of digital devices. Position sensors (21/31, 68%) and heart rate sensors and pulse rate sensors (12/31, 39%) were the most prevalent types of sensors used to acquire behavioral and physiological data in the SRs. In recent years, the clinical evidence concerning digital biomarkers has been systematically reviewed in a wide range of study populations, interventions, digital devices, and sensor technologies, with the dominance of physical activity and cardiac monitors. We used the World Health Organization's ICF tool for classifying behavioral and physiological data, which seemed to be an applicable tool to categorize the broad scope of digital biomarkers identified in this review. To understand the clinical value of digital biomarkers, the strength and quality of the evidence on their health consequences need to be systematically evaluated.


Optimal distribution of integration time for intensity measurements in Stokes polarimetry.
We consider the typical Stokes polarimetry system, which performs four intensity measurements to estimate a Stokes vector. We show that if the total integration time of intensity measurements is fixed, the variance of the Stokes vector estimator depends on the distribution of the integration time at four intensity measurements. Therefore, by optimizing the distribution of integration time, the variance of the Stokes vector estimator can be decreased. In this paper, we obtain the closed-form solution of the optimal distribution of integration time by employing Lagrange multiplier method. According to the theoretical analysis and real-world experiment, it is shown that the total variance of the Stokes vector estimator can be significantly decreased about 40% in the case discussed in this paper. The method proposed in this paper can effectively decrease the measurement variance and thus statistically improves the measurement accuracy of the polarimetric system.


Scrub typus fulminating as liver failure: A rare report.
Scrub typhus is almost an endemic tropical mite-borne, zoonotic illness often cognate with the bacterium Orientia tsutsugamushi. After a typical incubation period of a fortnight, non-specific symptoms including fever, headache, and a specific skin 'eschar' is customary. If untreated after a symptomatic week, scrub typus may precipitate end-organ involvements spiraling into vivid complications. Nevertheless, crub typhus tends to display mild transaminitis, frank liver failure is hardly common in clinical practice. An instance of scrub typus triggering fulminant hepatic failure (FHF) in a middle-aged female is being reported here.


Cerebral microbleeds: their associated factors, radiologic findings, and clinical implications.
Cerebral microbleeds (CMBs) are tiny, round dark-signal lesions that are most often detected on gradient-echo MR images. CMBs consist of extravasations of blood components through fragile microvascular walls characterized by lipohyalinosis and surrounding macrophages. The prevalence of CMBs in elderly subjects with no history of cerebrovascular disease is around 5%, but is much higher in patients with ischemic or hemorrhagic stroke. Development of CMBs is closely related to various vascular risk factors; in particular, lobar CMBs are thought to be associated with cerebral amyloid angiopathy. The presence of CMBs has been hypothesized to reflect cerebral-hemorrhage-prone status in patients with hypertension or amyloid microangiopathy. Stroke survivors with CMBs have been consistently found to have an elevated risk of subsequent hemorrhagic stroke or an antithrombotic-related hemorrhagic complication, although studies have failed to establish a link between CMBs and hemorrhagic transformation after thrombolytic treatment. A large prospective study is required to clarify the clinical significance of CMBs and their utility in a decision-making index.


Technical advances in the correction of septal perforation associated with closed rhinoplasty.
To demonstrate technical advances for closing septal perforations that allow the perforation repair to be performed with primary or revisional closed rhinoplasty during the same operation. We used this technique with closed rhinoseptoplasty in 258 cases of perforations in which the perforation ranged from 1.0 to 3.5 cm in diameter. We repaired the perforation using bilateral intranasal submucoperichondrial and submucoperiosteal advancement flaps with a sandwich graft interposition between. We prepared the sandwich graft using the auricular or septal cartilage and 2 layers of deep temporoparietal fascia. In every case, the septal perforation was corrected along with the closed rhinoseptoplasty and, because this is a conservative approach, the vascularization of the columella and anterior septum was preserved, with an excellent view of all the structures involved. Perforation repair represents a challenge to most surgeons owing to the low rates of successful correction with some techniques. Some of these techniques not only fail to rectify nasal aesthetics and the perforation during the same surgery but also cause undesired aesthetic alterations due to the retraction and rotation of tissues to close the perforation. We have performed this repair since 1989, allowing for closure of the perforation in 257 of 258 patients.


Accuracy of pedometer steps and time for youth with disabilities.
The purpose of the study was to examine the accuracy of pedometer steps and activity time (Walk4Life, WL) for youth with developmental disabilities. Eighteen youth (11 girls, 7 boys) 4-14 years completed six 80-meter self-paced walking trials while wearing a pedometer at five waist locations (front right, front left, back right, back left, middle back). Trials were video taped to determine actual steps and activity time. Time exhibited a smaller percent error in comparison to steps across locations. Apart from the front left, location had minimal influence on accuracy. The WL demonstrates acceptable accuracy for steps and activity time.


Pathogenesis of refractory secondary hyperparathyroidism.
Calcitriol is currently used to reduce parathyroid hormone (PTH) levels in uremic patients. However, a significant number of patients fail to respond to calcitriol therapy. The data suggest that a poor response to calcitriol can be anticipated in patients with severe hyperparathyroidism (with a high basal PTH levels) and uncontrolled serum phosphate. The abnormal parathyroid response to calcitriol in uremic patients with severe parathyroid hyperplasia may be attributed, to a large extent, to the development of nodular hyperplasia as a result of clonal transformation from a diffuse polyclonal hyperplasia. The factors involved in the development of polyclonal parathyroid hyperplasia, at earlier stages of secondary hyperparathyroidism, appear to be the same factors that stimulate PTH secretion and synthesis: hypocalcemia, hyperphosphatemia and low serum calcitriol levels. Studies performed in vitro using parathyroid tissue from uremic patients who required parathyroidectomy demonstrate that in nodular hyperplasia there is an abnormal response to calcium and calcitriol, which suggests that there are factors intrinsic to the hyperplastic cell (such as decrease in calcium sensor receptors and vitamin D receptors) responsible for an abnormal regulation of parathyroid function. Accumulation of phosphate is a key factor in the pathogenesis of secondary hyperparathyroidism and a poor response to calcitriol treatment is associated with the failure to control the serum phosphorus. High phosphate stimulates PTH secretion as demonstrated by in vivo and in vitro studies. In addition, animal studies strongly suggest that phosphate increases parathyroid cell proliferation. There are growth-related genes potentially involved in uremic hyperparathyroidism; however, changes in the expression of these genes may be the consequence rather than the cause of parathyroid hyperplasia.


Truncating mutations of TP53AIP1 gene predispose to cutaneous melanoma.
Genetic predisposition to cutaneous malignant melanoma (CMM) involves highly penetrant predisposing genes and low and intermediate penetrant predisposing alleles. However, the missing heritability in (CMM) is still high. For such and in order to identify new genetic factors for CMM, we conducted an exome sequencing study in high-risk CMM patients. Two rounds of exome sequencing were successively performed in 33 and 27 high-risk patients. We focused on genes carrying rare nonsense, frameshift, and splice variants (allelic frequency <1%) that were present in both series of exomes. An extension study was then conducted in a large cohort (1 079 CMM patients and 1 230 Caucasian ethnically matched healthy controls), and the inactivating variants frequency was compared between groups using two-sided Fisher exact test. Two TP53AIP1 truncating mutations were identified in four patients: a frameshift c.63_64insG, p.Q22Afs*81 in two patients from the same family and in the proband of a second family; and a nonsense mutation c.95 C > A, p.Ser32Stop in a patient with multiple CMMs. In all patients, TP53AIP1 truncating variants were strongly associated with CMM risk (two-sided Fisher exact test = 0.004, OR = 3.3[1.3-8.5]). Additionally, we showed that TP53AIP1 mRNA was strongly down-regulated throughout different phases of melanoma progression. TP53AIP1 gene is a TP53 target which plays a key role by inducting apoptosis in response to UV-induced DNA damage. Constitutional mutations of TP53AIP1 had previously been involved in susceptibility to prostate cancer. Our results show that constitutional truncating TP53AIP1 mutations predispose to CMM in the French population. Replication studies in other populations should be performed.


Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility.
Congenital aganglionic megacolon, commonly known as Hirschsprung disease (HSCR), is the most frequent cause of congenital bowel obstruction. Germline mutations in the RET receptor tyrosine kinase have been shown to cause HSCR. Knockout mice for RET and for its ligand, glial cell line-derived neurotrophic factor (GDNF), exhibit both complete intestinal aganglionosis and renal defects. Recently, GDNF and GFRA1 (GDNF family receptor, also known as GDNFR-alpha), its GPI-linked coreceptor, were demonstrated to be components of a functional ligand for RET. Moreover, GDNF has been implicated in rare cases of HSCR. We have mapped GFRA1 to human chromosome 10q25, isolated human and mouse genomic clones, determined the gene's intron-exon boundaries, isolated a highly polymorphic microsatellite marker adjacent to exon 7, and scanned for GFRA1 mutations in a large panel of HSCR patients. No evidence of linkage was detected in HSCR kindreds, and no sequence variants were found to be in significant excess in patients. These data suggest that GFRA1'S role in enteric neurogenesis in humans remains to be elucidated and that RET signaling in the gut may take place via alternate pathways, such as the recently described GDNF-related molecule neurturin and its GFRA1-like coreceptor, GFRA2.


Intrapalpebral Extending Dysesthetic Bleb Revision with Fibrin Glue.
This pilot study evaluates the safety and efficacy of a novel surgical technique using fibrin glue to treat bleb dysesthesia post-trabeculectomy due to intrapalpebral extension. Trabeculectomy remains the gold standard for control of intraocular pressure (IOP) in refractory glaucoma. Bleb dysesthesia following antifibrotic-enhanced trabeculectomy is common, resulting in a significant decrease in quality of life. Symptoms include pain, foreign body sensation, and excessive tearing. Treatments include lubrication, topical nonsteroidal anti-inflammatory drugs (NSAIDs), bandage contact lens, bleb needling, compression sutures, Nd:YAG laser treatments, autologous blood injection, and cryopexy. These procedures can be time-consuming, risk bleb function, and may be ineffective at symptom control; thus, a novel technique is required. This is a retrospective case series of eyes undergoing bleb dissection with scleral cutdown and conjunctival closure with ARTISS fibrin tissue glue. Reported cases have been followed up for 6 months. Outcomes assessed include complications, IOP, medication usage, subjective pain score, visual field, and cup-to-disk (C:D) ratio. This small pilot series demonstrated that patients suffering from bleb dysesthesia due to intrapalpebral bleb extension can be successfully treated with a novel surgical approach combining conjunctival dissection to sclera with fibrin tissue glue closure. There was no significant effect on bleb function and no contribution to glaucoma progression over a 6-month period. A significant reduction in patient discomfort with no new surgical complications was noted. This demonstrates a safe and effective novel surgical approach to treat patients with this condition. The technique is easily learnt and can be employed in an outpatient setting. The technique is readily accepted by patients in group who are often reticent to undergo further intervention. Most importantly, it does not compromise bleb function or destabilize glaucoma control. Holmes DP, Manning DK. Intrapalpebral Extending Dysesthetic Bleb Revision with Fibrin Glue. J Curr Glaucoma Pract 2020;14(1):37-42.


Speech Recognition Outcomes in Adults With Slim Straight and Slim Modiolar Cochlear Implant Electrode Arrays.
To compare differences in audiologic outcomes between slim modiolar electrode (SME) CI532 and slim lateral wall electrode (SLW) CI522 cochlear implant recipients. Retrospective cohort study. Tertiary academic hospital. Comparison of postoperative AzBio sentence scores in quiet (percentage correct) in adult cochlear implant recipients with SME or SLW matched for preoperative AzBio sentence scores in quiet and aided and unaided pure tone average. Patients with SLW (n = 52) and patients with SME (n = 37) had a similar mean (SD) age (62.0 [18.2] vs 62.6 [14.6] years, respectively), mean preoperative aided pure tone average (55.9 [20.4] vs 58.1 [16.4] dB; P = .59), and mean AzBio score (percentage correct, 11.1% [13.3%] vs 8.0% [11.5%]; P = .25). At last follow-up (SLW vs SME, 9.0 [2.9] vs 9.9 [2.6] months), postoperative mean AzBio scores in quiet were not significantly different (percentage correct, 70.8% [21.3%] vs 65.6% [24.5%]; P = .29), and data log usage was similar (12.9 [4.0] vs 11.3 [4.1] hours; P = .07). In patients with preoperative AzBio <10% correct, the 6-month mean AzBio scores were significantly better with SLW than SME (percentage correct, 70.6% [22.9%] vs 53.9% [30.3%]; P = .02). The intraoperative tip rollover rate was 8% for SME and 0% for SLW. Cochlear implantation with SLW and SME provides comparable improvement in audiologic functioning. SME does not exhibit superior speech recognition outcomes when compared with SLW.


Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man.
beta 2-IFN/hepatocyte stimulating factor/IL-6 is a cytokine secreted by monocytes, fibroblasts, and endothelial cells in cell culture that possesses diverse biologic activity including the stimulation of acute phase plasma protein synthesis and immunomodulation. The circulating levels of this cytokine in man in response to bacterial LPS (endotoxin) were studied. A single i.v. bolus of endotoxin (20 U/kg) produced a monophasic rise in circulating immunoreactive IFN-beta 2/IL-6 and IFN-beta 2/IL-6 bioactivity (hepatocyte stimulation and B cell differentiation assays) peaking 2 to 4 h after the endotoxin challenge. Peak IFN-beta 2/IL-6 levels ranged from 4.1 to 27.5 ng/ml. Associated with this was a rise in circulating C-reactive protein levels detected 20 h after the endotoxin bolus. Thus, IFN-beta 2/IL-6 is likely one of the endogenous mediators which is triggered in man during bacterial infection and likely participates in the metabolic and immune responses of the infected host.


Glucosinolate-Degradation Products as Co-Adjuvant Therapy on Prostate Cancer in Vitro.
Glucosinolate-degradation products (GS-degradation products) are believed to be responsible for the anticancer effects of cruciferous vegetables. Furthermore, they could improve the efficacy and reduce side-effects of chemotherapy. The aim of the present study was to determine the cytotoxic effects of GS-degradation products on androgen-insensitive human prostate cancer (AIPC) PC-3 and DU 145 cells and investigate their ability to sensitize such cells to chemotherapeutic drug Docetaxel (DOCE). Cells were cultured under growing concentrations of allyl-isothiocyanate (AITC), sulforaphane (SFN), 4-pentenyl-isothiocyanate (4PI), iberin (IB), indole-3-carbinol (I3C), or phenethyl-isothiocyanate (PEITC) in absence or presence of DOCE. The anti-tumor effects of these compounds were analyzed using the trypan blue exclusion, apoptosis, invasion and RT-qPCR assays and confocal microscopy. We observed that AITC, SFN, IB, and/or PEITC induced a dose- and time-dependent cytotoxic effect on PC-3 and DU 145 cells, which was mediated, at least, by apoptosis and cell cycle arrest. Likewise, we showed that these GS-degradation products sensitized both cell lines to DOCE by synergic mechanisms. Taken together, our results indicate that GS-degradation products can be promising compounds as co-adjuvant therapy in prostate cancer.


Optic Neuropathy Associated with Primary Sjögren's Syndrome: A Case Series.
To determine the diverse clinical features of optic neuropathy associated with primary Sjögren's syndrome in Korean patients. Five women with acute and/or chronic optic neuropathy who were diagnosed as primary Sjögren's syndrome were retrospectively evaluated. Primary Sjögren's syndrome was diagnosed by signs and symptoms of keratoconjunctivitis sicca, positive serum anti-Ro/SSA and/or anti-La/SSB antibodies, and/or minor salivary gland biopsy. All patients underwent a complete ophthalmologic examination. Among the five patients diagnosed as optic neuropathy related to primary Sjögren's syndrome, four patients had bilateral optic neuropathy and one patient was unilateral. The clinical course was chronic in three patients and one of them showed acute exacerbation and was finally diagnosed with neuromyelitis optica spectrum disorder. The other two patients presented as acute optic neuritis and one was diagnosed with neuromyelitis optica spectrum disorder. Sicca symptoms were present in four patients, but only two patients reported these symptoms before the onset of optic neuropathy. Patients showed minimal response to systemic corticosteroids or steroid dependence, requiring plasmapheresis in the acute phase and immunosuppressive agents for maintenance therapy. Optic neuropathy associated with primary Sjögren's syndrome may show variable clinical courses, including acute optic neuritis, insidious progression of chronic optic atrophy, or in the context of neuromyelitis optica spectrum disorders. Optic neuropathy may be the initial manifestation of primary Sjögren's syndrome without apparent sicca symptoms, which makes the diagnosis often difficult. The presence of specific antibodies including anti-Ro/SSA, anti-La/SSB, and anti-aquaporin-4 antibodies are supportive for the diagnosis and treatment in atypical cases of optic neuropathy.


Causes of neuromuscular weakness in the intensive care unit: a study of ninety-two patients.
The spectrum of neuromuscular disorders among intensive care unit (ICU) patients has shifted toward disorders acquired within the ICU and away from "traditional" neuromuscular disorders that lead to ICU admission. We sought to assess this spectrum by determining the causes and relative frequencies of neuromuscular disorders that led to electromyography (EMG) examinations in our ICU population. Ninety-two patients were studied over a 4 1/2-year period. Twenty-six (28%) had neuromuscular disorders (mainly Guillain-Barré syndrome, myopathy, and motor neuron disease) that led to ICU admission. Among patients who developed weakness in the ICU, there was a predominance of organ transplant patients and patients with the systemic inflammatory response syndrome and multiorgan dysfunction. Thirty-nine (42%) developed acute myopathy (consistent with critical illness myopathy in most), and 13% developed acute axonal sensorimotor polyneuropathy (mainly critical illness polyneuropathy). Patients with acute myopathy and acute axonal sensorimotor polyneuropathy had similar functional outcomes. We conclude that among patients who underwent EMG in our ICU population, acute myopathy is three times as common as acute axonal polyneuropathy, and the outcomes from acute myopathy and acute axonal polyneuropathy may be similar.


Computed tomography guided fine needle aspiration cytology in the diagnosis of thoracic lesions.
Computed tomography (CT) allows the performance of fine needle aspiration cytology (FNAC) in situations in which ultrasound or conventional x-rays do not correctly visualise the lesion or the needle tract. Over an 18-month period 184 patients underwent CT-guided FNAC of thoracic lesions. Of these 140 patients presented with pulmonary parenchymal lesions, 18 with mediastinal lesions, 14 with pleural lesions and 12 with hilar lymphadenopathy. A categorical diagnosis was possible in 180 (98%) cases. In majority of the cases only one or two passes were required. Two cases developed pneumothorax and required chest drainage. It can be concluded from the present observations that FNAC under CT control is a useful and accurate diagnostic technique.