Glutathione-Depleting Organic Metal Adjuvants for Effective NIR-II Photothermal Immunotherapy.
Although photothermal immunotherapy (PTI) is a compelling strategy for tumor therapy, the development of promising photothermal agents to overcome the insufficient immunogenicity of tumor cells and the poor immune response encountered in PTI is still challenging. Herein, commercial small-molecule-based organic metal adjuvants (OMAs) are presented, with second near-infrared photoacoustic and photothermal properties as well as the ability to perturb redox homeostasis to potentiate immunogenicity and immune responsiveness. OMAs, assembled from charge-transfer complexes and characterized by a broad substrate scope, high accessibility, and flexibly tuned optical properties, demonstrate strong phototherapeutic and adjuvant abilities via the depletion of glutathione and cysteine, and subsequently elicit systemic immunity by evoking immunogenic cell death, promoting dendritic cell maturation, and increasing T cell infiltration. Furthermore, programmed cell death protein 1 antibody can be employed to synergize with OMAs to suppress tumor immune evasion and ultimately improve the treatment outcomes. This study unlocks new paradigms to provide a versatile OMA-based scaffold for future practical applications.


Haptoglobin Therapeutics and Compartmentalization of Cell-Free Hemoglobin Toxicity.
Hemolysis and accumulation of cell-free hemoglobin (Hb) in the circulation or in confined tissue compartments such as the subarachnoid space is an important driver of disease. Haptoglobin is the Hb binding and clearance protein in human plasma and an efficient antagonist of Hb toxicity resulting from physiological red blood cell turnover. However, endogenous concentrations of haptoglobin are insufficient to provide protection against Hb-driven disease processes in conditions such as sickle cell anemia, sepsis, transfusion reactions, medical-device associated hemolysis, or after a subarachnoid hemorrhage. As a result, there is increasing interest in developing haptoglobin therapeutics to target 'toxic' cell-free Hb exposures. Here, we discuss key concepts of Hb toxicity and provide a perspective on the use of haptoglobin as a therapeutic protein.


Human EEG and artificial neural networks reveal disentangled representations of object real-world size in natural images.
Human brains have the ability to accurately perceive and process the real-world size of objects, despite vast differences in distance and perspective, which is a remarkable feat of cognitive processing. While previous studies have delved into this phenomenon, our study uses an innovative approach to disentangle neural representations of object real-world size from visual size and perceived real-world depth in a way that was not previously possible. Our multi-modal approach incorporates computational modeling and the THINGS EEG2 dataset, which offers both high time-resolution human brain recordings and more ecologically valid naturalistic stimuli. Leveraging this state-of-the-art dataset, our EEG representational similarity results revealed a pure representation of object real-world size in human brains. We report a representational timeline of visual object processing: pixel-wise differences appeared first, then real-world depth and visual size, and finally, real-world size. Furthermore, representational comparisons with different artificial neural networks reveal real-world size as a stable and higher-level dimension in object space incorporating both visual and semantic information.


Environmental risk assessment of clinical trials involving modified vaccinia virus Ankara (MVA)-based vectors.
The modified vaccinia virus Ankara (MVA) strain, which has been developed as a vaccine against smallpox, is since the nineties widely tested in clinical trials as recombinant vector for vaccination or gene therapy applications. Although MVA is renowned for its safety, several biosafety aspects need to be considered when performing the risk assessment of a recombinant MVA (rMVA). This paper presents the biosafety issues and the main lessons learned from the evaluation of the clinical trials with rMVA performed in Belgium. Factors such as the specific characteristics of the rMVA, the inserted foreign sequences/transgene, its ability for reconversion, recombination and dissemination in the population and the environment are the main points of attention. Measures to prevent or manage identified risks are also discussed.


A survey of podiatric medical students' computer literacy.
This article reviews the extent of health-care students' computer literacy and presents the results of a survey of podiatric medical students' computer literacy. The results of this survey indicate that podiatric medical students are more likely than other health-care students to rate their computer literacy as good or very good. There was no gender difference in this self-reported computer knowledge. The implications for designing and using Web-based instructional materials and technology for podiatric medical students are discussed.


Social tolerance allows cooperation to prevail in an adaptive environment.
In real situations, individuals often have moderate tolerance toward ambient cooperative environment in which they tend to avoid unfavorable interactions and search for favorable ones. How such social tolerance affects the evolution of cooperation and the resulting cooperative networks remains to be answered. To address this issue, here we present an effective model of co-evolutionary prisoner's dilemma by introducing cooperative environment and social tolerance for networked players. An individual's level of cooperative environment characterizes the cooperativity and sustainability of its interaction environment centered on itself. In our model, for paired individuals we assume that the one in better cooperative environment has a certain tolerance threshold to the opponent. If the opponent's cooperative environment level is beyond the tolerance threshold, the one in better cooperative environment cuts unilaterally the link, and rewires to others. Otherwise, the link is not severed, and meanwhile an inhomogeneous strategy imitation process between them is considered. Moreover, a player's cooperative environment is adjusted in response to the strategy choices in the neighborhood. Interestingly, we find that there exists a moderate tolerance threshold warranting the best promotion of cooperation. We explain the nontrivial results by investigating the time ratio of strategy (network) updating during the whole process and properties in emerging networks. Furthermore, we investigate the effect of memory-dependent discounting of individuals' cooperative environment on the evolution of cooperation. We also demonstrate the robustness of our results by considering two other modified co-evolutionary rules. Our results highlight the importance of appropriate tolerance threshold for the evolution of cooperation during the entangled co-evolution of strategy and structure.


Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion.
It is generally assumed that the functional consequences of stimulation with Ca2+ -mobilizing agonists are derived exclusively from the second messenger action of intracellular Ca2+, acting on targets inside the cells. However, during Ca2+ signaling events, Ca2+ moves in and out of the cell, causing changes not only in intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous cell types possess an extracellular Ca2+ "sensor" raises the question of whether these dynamic changes in external [Ca2+] may serve some sort of messenger function. We found that in intact gastric mucosa, the changes in extracellular [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were sufficient and necessary to elicit alkaline secretion and pepsinogen secretion, independent of intracellular [Ca2+] changes. These findings suggest that extracellular Ca2+ can act as a "third messenger" via Ca2+ sensor(s) to regulate specific subsets of tissue function previously assumed to be under the direct control of intracellular Ca2+.


Middle Meningeal Artery Embolization for Chronic Subdural Hematoma Related to Autosomal Dominant Polycystic Kidney Disease.
Autosomal dominant polycystic kidney disease (ADPKD) is a connective tissue disease with vascular abnormalities involving multiple organs. The prevalence of ADPKD associated with a spontaneous subdural hematoma (SDH) is very low, with less than 10 cases reported in the literature to date. Symptomatic chronic SDH is classically treated with a twist drill, burr holes, or craniotomy. Recently, middle meningeal artery (MMA) embolization has emerged as an ancillary modality. We present the first case in the literature of a bilateral SDH in a young ADPKD patient successfully managed with MMA embolization. Moreover, we discuss the role of different treatment modalities on this subset of patients.


[CRISPR-Cas9 for muscle dystrophies].
Muscular dystrophies are a group of rare muscular disorders characterized by weakness and progressive degeneration of the muscle. They are diseases of genetic origin caused by the mutation of one or more genes involved in muscle function. Despite significant progress made in the field of biotherapies in recent years, there is as yet no curative treatment available for these diseases. Studies conducted since the discovery of the CRISPR-Cas9 genomic editing tool have nevertheless led to significant and promising advances in the treatment of muscular dystrophies. CRISPR-Cas9 system allows a stable and permanent edition of the genome and should make it possible to avoid long, partially efficient and repetitive treatments. In this review, we will discuss the latest therapeutic advances obtained using the CRISPR-Cas9 system in genetic muscular dystrophies.


[Association between glutathione-S-transferase gene polymorphisms (GSTM1, GSTT1 and GSTP1) and idiopathic azoospermia].
To assess the association between glutathione-S-transferase gene polymorphisms GSTT1, GSTM1 and GSTP1 and onset of azoospermia. Multi-PCR was used to detect GSTM1 and GSTT1 gene deletions. Polymorphisms of GSTP1 were determined with restriction fragment length polymorphism (RFLP) method in 236 azoospermia patients and 142 healthy fertile male controls. The frequency of M1 (-/-) and P1 (Ile/Val or Val/Val) genotype was 24.65% in the control group, which was significantly higher than that of the patient group (15.68%, P=0.031). Frequency of M1 (-/-), T1 (+/+) and P1 (Ile/Val or Val/Val) genotype was 12.68% in the control group, which was significantly higher than that of the patient group (5.51%, P=0.014). The M1(-/-) and P1(Ile/Val or Val/Val) genotype and the M1(-/-), T1(+/+) and P1 (Ile/Val or Val/Val) genotype are associated with reduced risk of azoospermia in ethnic Chinese Han population.


Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients.
The purpose of this randomized, double-blind parallel group study was to compare the safety, tolerability and acceptability of Easyhaler and Turbuhaler dry powder inhalers for the delivery of budesonide 800 microg day(-1) in adult asthmatic patients who had already been treated with inhaled corticosteroids for at least 6 months prior to the study Additionally the efficacy of the products was evaluated. The main objective was to evaluate the systemic safety of budesonide inhaled from Easyhaler (Giona Easyhaler, Orion Pharma, Finland) as determined by serum and urine cortisol measurements. The secondary objective was to compare the tolerability acceptability and efficacy of the two devices in the administration of budesonide. After a 2-week run-in period (baseline), patients were randomized on a 2:1 basis to receive budesonide from Easyhaler (n = 103) or from Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Sweden) (n = 58) 200 g dose(-1), two inhalations twice daily for 12 weeks. There was no statistically significant change in morning serum cortisol values from baseline to the end of treatment in either group. Urine free cortisol and urine cortisol/ creatinine ratio increased from baseline in both groups. There were no significant differences between the groups in terms of morning serum cortisol, urine cortisol, adverse events or efficacy variables, but Easyhaler was generally considered more acceptable to the patients. In conclusion, at 800 microg day(-1), Giona Easyhaler is as safe and efficacious as Pulmicort Turbuhaler in adult asthmatic patients previously treated with corticosteroids, but more acceptable to patients.


[Risk assessment and management of exodontia perioperative patients with cardiovascular diseases].
The number of tooth extraction patients with cardiovascular disease in our country is increasing year by year. Safety is essential for those patients and there is no uniform standard of risk assessment and management for tooth extraction patients with cardiovascular disease during perioperative period. By referring to literatures and with the clinical experience, the author summarized the risk assessment methods for tooth extraction patients with cardiovascular disease during perioperative period. Blood pressure control, cardiac function determination, arrhythmia recognition, blood glucose management, oral antiplatelet or anticoagulant medicine use, etc, were proposed in this article.


A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.
A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893-902. ©2017 AACR.


Levels of CD105+ cells increase and cell proliferation decreases during S-phase arrest of amniotic fluid cells in long-term culture.
The present study aimed to improve the characterization of amniotic fluid cells (AFCs) in order to optimize their use in chromosomal prenatal diagnosis and as seed or stem cells for tissue engineering. The AFCs used in the current study were obtained from three females in their second trimester of pregnancy. The cells were cultured independently and characterized by cell morphology, cell markers, cell cycle distribution and chromosome Giemsa banding in an early- and late-passage. The AFCs remained homogeneous in culture and expressed mesenchymal markers, but not endothelial markers along the culture process. In addition, compared with the early-passage cells, the late-passage cells exhibit an increase in CD105 expression, a decrease in cell division and a delay in the cell cycle, and a number of cells underwent cell cycle arrest. However, the cells retained a normal karyotype. Therefore, the current study characterized AFCs in a clinical culture and confirmed that AFCs are mesenchymal precursors. The results obtained may be useful for the application of AFCs in prenatal diagnosis.


Bimanual grasping does not adhere to Weber's law.
According to Weber's law, a fundamental principle of perception, visual resolution decreases in a linear fashion with an increase in object size. Previous studies have shown, however, that unlike for perception, grasping does not adhere to Weber's law. Yet, this research was limited by the fact that perception and grasping were examined for a restricted range of stimulus sizes bounded by the maximum fingers span. The purpose of the current study was to test the generality of the dissociation between perception and action across a different type of visuomotor task, that of bimanual grasping. Bimanual grasping also allows to effectively measure visual resolution during perception and action across a wide range of stimulus sizes compared to unimanual grasps. Participants grasped or estimated the sizes of large objects using both their hands. The results showed that bimanual grasps violated Weber's law throughout the entire movement trajectory. In contrast, Just Noticeable Differences (JNDs) for perceptual estimations of the objects increased linearly with size, in agreement with Weber's law. The findings suggest that visuomotor control, across different types of actions and for a large range of size, is based on absolute rather than on relative representation of object size.


Aptamers and Their Significant Role in Cancer Therapy and Diagnosis.
Aptamers are nucleic acid/peptide molecules that can be generated by a sophisticated, well-established technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers can interact with their targets through structural recognition, as in antibodies, though with higher specificity. With this added advantage, they can be made useful for clinical applications such as targeted therapy and diagnosis. In this review, we have discussed the steps involved in SELEX process and modifications executed to attain high affinity nucleic acid aptamers. Moreover, our review also highlights the therapeutic applications of aptamer functionalized nanoparticles and nucleic acids as chemo-therapeutic agents. In addition, we have described the development of "aptasensor" in clinical diagnostic application for detecting cancer cells and the use of aptamers in different routine imaging techniques, such as Positron Emission Tomography/Computed Tomography, Ultrasound, and Magnetic Resonance Imaging.


[Usefulness of the residual SYNTAX score to predict long term outcome in acute coronary syndrome patients underwent percutaneous coronary intervention].
Objective: To quantify the extent and complexity of residual coronary stenosis following PCI by the residual SYNTAX score, and to evaluate its impact on adverse ischemic outcomes in acute coronary syndrome(ACS) patients. Methods: From January 2013 to December 2013, a total of 1 414 consecutive moderate- and high-risk ACS patients who underwent any PCI with multi-vessel coronary artery disease were evaluated.Patients were stratified by rSS quartiles and their outcomes were compared. Results: The rSS was 4.8±6.7. 591 patients (41.8%) had rSS=0(CR), 233 patients (16.5%) had rSS>0 but ≤ 3, 296 patients (20.9%) had rSS>3 but ≤8 and 294 patients (20.8%) had rSS>8.Clinical risk factors were more frequent in patients with incomplete revascularization(IR) compared with complete revascularization(CR). The 2-year rates of all-caused death(1.2% vs 0.4%, 2.0%, 4.4%, P=0.003), cardiac death, revascularization and MACCE were significantly higher in high rSS group, compared to other groups.By multivariable analysis, rSS was a strong independent predictor of ischemic outcomes at 2-year, including all-cause mortality (HR=1.05, 95%CI 1.01-1.09, P=0.019), cardiac death, revascularization and MACCE. Conclusions: The rSS is a strong independent predictor of all-caused death, cardiac death, revascularization and MACCE and has moderated predictive ability for those ischemic outcomes.


Cooperation of Ito cells and hepatocytes in the deposition of an extracellular matrix in vitro.
Cellular and molecular mechanisms involved in the deposition of extracellular matrix components in both normal and fibrotic liver are still poorly understood. We have investigated the influence of cooperation between Ito cells and hepatocytes in matrix deposition in vitro. Immunoprecipitation of radiolabeled proteins from media of 5-day-old Ito cell primary cultures showed that these cells secreted high levels of the major basement membrane components, ie, collagen IV, laminin, and entactin/nidogen. By immunocytochemistry, precursors of basement membrane components were found intracellularly, but only scarce deposits were seen around the cells. When hepatocytes were added to 2-day-old Ito cell primary cultures, they established close contacts with Ito cells in less than 24 hours and expressed ZO-1, a tight junction-associated protein not detectable in standard hepatocyte culture. Cytochemistry analysis revealed an abundant extracellular matrix deposited over hepatocyte cords and between hepatocytes and Ito cells. Immunocytochemistry studies showed that this matrix contained laminin, fibronectin, and collagens proIII and IV. These data indicate that a high level of matrix protein synthesis by liver cells in vitro is not sufficient to induce extracellular matrix deposition, and that cell-cell interactions are strongly involved in this process. Hepatocyte/Ito cell co-culture, which may reflect the actual situation in vivo, represents a useful tool for studying liver fibrogenesis.


[Left behind populations, COVID-19 and risks of health inequities : a guide of the local social-health network (Vaud, Switzerland)].
Since the emergence of the COVID-19 pandemic, the Confederation has referred to « vulnerable populations » over the age of 65 and/or with co-morbidities as potentially at risk. This group should not overshadow other highly vulnerable populations such as forced migrants, people deprived of their liberty, and the homeless. In the context of the current pandemic, there is a risk of increasing inequities in care among these populations. In this practical article, we list the marginalized and disadvantaged left behind populations in the canton of Vaud and the issues of inequities in care in the context of the pandemic; we also present the implementation of procedures sometimes original, always inter-professional and interdisciplinary, specifying who the partners are and what the resources are for front-line caregivers.


The role of bladder function in the pathogenesis and treatment of urinary tract infections in toilet-trained children.
Urinary tract infections (UTIs) are a common reason for referral to pediatric specialists and the risk profile of these children is influenced by age, sex, and underlying urinary tract abnormalities. UTIs in toilet-trained children represent a different entity than confirmed, febrile UTIs that occur in infants, impacted by suboptimal bladder habits, bladder dysfunction, constipation, or a combination of these factors. A comprehensive literature search was conducted using PubMed and MEDLINE and search terms included recurrent UTI, VUR, bladder and bowel dysfunction (BBD), constipation, lower urinary tract symptoms, and voiding dysfunction. Common presenting symptoms of UTI in children include fever (> 38 °C) with or without "traditional" lower urinary tract symptoms (LUTS) such as dysuria, malodorous urine, frequency, urgency, and incontinence. However, many infections in older children are afebrile episodes-consisting primarily of LUTS-which may or may not be confirmed with biochemical and/or microbiological evidence. Therefore, when evaluating toilet-trained children with recurrent UTIs, it is paramount to consider dysfunctional elimination as an underlying cause, diagnose, and treat it prior to indicating surgical options, even in the presence of VUR or other anatomical abnormalities. Although the impact of bladder function on the risk of infections is important, so is the accurate diagnosis and initial evaluation. This review article will focus on an often overlooked yet critical factor: the impact of bladder function, particularly for toilet-trained children, as well as the importance of implementing bladder training strategies, aggressive management of constipation, and pharmacological management as necessary.


Gustatory sweating due to autonomic neuropathy in a patient with amyloidosis secondary to rheumatoid arthritis.
Abstract Autonomic neuropathy, although often reported to occur in patients with AL (amyloid of light chain of immunoglobulin) amyloidosis, is extremely rare in AA (amyloid A) amyloidosis. We describe a patient with AA amyloidosis secondary to rheumatoid arthritis (RA) in whom autonomic neuropathy resulted in gustatory sweating during the end stage of RA. We discuss the importance of gustatory sweating as a characteristic sign of autonomic nervous system dysfunction in AA amyloidosis secondary to RA, and stress the availability of cardiovascular autonomic tests as an indicator of autonomic neuropathy in not only AL amyloidosis but also AA amyloidosis.


Establishment of a human small-cell lung-cancer subline resistant to okadaic acid.
Okadaic acid (OA), a specific protein phosphatase inhibitor, has various biological functions. To elucidate the mechanism of OA resistance, we have established a small-cell lung-cancer subline (H69/OA100) resistant to the growth-inhibitory effect of OA; this was done by using the parental cell line (H69) and increasing the concentration of OA. H69/OA100 was about 8 times more resistant to OA than H69. Intracellular retention of the fluorescent OA derivative in H69/OA100 was the same as that in H69. The catalytic activity of protein phosphatase from H69/OA100 was significantly reduced compared with that from H69. The protein phosphatase from H69/OA100 was 3.6 times more resistant to OA than that from H69. We examined the effect of OA on the activity of the immunoprecipitated protein phosphatase type I (PPI) and type 2A (PP2A) from the 2 cell lines. The PPI and PP2A from H69/OA100 showed more resistance to OA than those from H69. We next examined the effect of OA on the cell cycle of H69 and H69/OA100. In H69, G2/M block was observed at an OA concentration of 30 ng/ml whereas in H69/OA100, no G2/M block was observed at concentrations up to 100 ng/ml OA. We finally evaluated the amount of p34cdc2 kinase expression and the phosphorylation status of p34cdc2. There was no difference in p34cdc2 expression between H69 and H69/OA100 at several concentrations of OA. However, dephosphorylation of p34cdc2 was observed at 30 ng/ml OA in H69, but not in H69/OA100 up to 100 ng/ml OA. These data suggest that the resistance to OA and the resistance of the cell-cycle block to OA in H69/OA100 might be due to alteration of protein phosphatase activity.


Aligned Poly(ε-caprolactone) Nanofibers Guide the Orientation and Migration of Human Pluripotent Stem Cell-Derived Neurons, Astrocytes, and Oligodendrocyte Precursor Cells In Vitro.
Stem cell transplantations for spinal cord injury (SCI) have been studied extensively for the past decade in order to replace the damaged tissue with human pluripotent stem cell (hPSC)-derived neural cells. Transplanted cells may, however, benefit from supporting and guiding structures or scaffolds in order to remain viable and integrate into the host tissue. Biomaterials can be used as supporting scaffolds, as they mimic the characteristics of the natural cellular environment. In this study, hPSC-derived neurons, astrocytes, and oligodendrocyte precursor cells (OPCs) are cultured on aligned poly(ε-caprolactone) nanofiber platforms, which guide cell orientation to resemble that of spinal cord in vivo. All cell types are shown to efficiently spread over the nanofiber platform and orient according to the fiber alignment. Human neurons and astrocytes require extracellular matrix molecule coating for the nanofibers, but OPCs grow on nanofibers without additional treatment. Furthermore, the nanofiber platform is combined with a 3D hydrogel scaffold with controlled thickness, and nanofiber-mediated orientation of hPSC-derived neurons is also demonstrated in a 3D environment. In this work, clinically relevant materials and substrates for nanofibers, fiber coatings, and hydrogel scaffolds are used and combined with cells suitable for developing functional cell grafts for SCI repair.


Investigation of fiber Bragg grating based mode-splitting resonant sensors.
In this paper, we report on theoretical investigation of split mode resonant sensors based on fiber Bragg grating (FBG) ring resonators and π-shifted fiber Bragg grating (π-FBG) ring resonators. By using a π-shifted Bragg grating ring resonator (π-FBGRR) instead of a conventional fiber Bragg grating ring resonator (FBGRR), the symmetric and antisymmetric resonance branches (i.e., the eigen-modes of the perturbed system) show peculiar and very important features that can be exploited to improve the performance of the fiber optic spectroscopic sensors. In particular, the π-FBGRR symmetric resonance branch can be taylored to have a maximum splitting sensitivity to small environmental perturbations. This optimal condition has been found around the crossing points of the two asymmetric resonance branches, by properly choosing the physical parameters of the system. Then, high sensitivity splitting mode sensors are theoretically demonstrated showing, as an example, a strain sensitivity improvement of at least one order of magnitude over the state-of-the-art.


Molecular detection of Mycobacterium leprae using RLEP-PCR in post elimination era of leprosy.
Leprosy is considered as a contagious disease and is still a health problem in several countries including India. Diagnosis of leprosy is based either on clinical findings or on acid fast bacilli staining. Due to low sensitivity of acid fast bacilli staining most of the leprosy cases were remained undetected. The present study aims to assess the efficacy of RLEP-PCR in the field condition where majority of the patients are acid fast bacilli negative and have early disease. A total of 80 suspected leprosy cases were recruited. Slit skin smear samples were taken for microscopy and molecular experimentation. DNA was extracted and RLEP-PCR was executed for all the 80 samples. To establish the statistical correlation χ2 test and Fisher's exact test were made. To elucidate the sensitivity of the test Receiver Operating Characteristic (ROC) was drawn. These 80 leprosy patients comprised of 38 paucibacillary and 42 multibacillary leprosy cases. Of 80 leprosy patients 18 (22.5%) were AFB positive while 53 (66.25%) leprosy cases were RLEP-PCR positive. The results of test of significance (P=0.0001) and Cohen's kappa coefficient (κ) (0.614) indicated that the RLEP-PCR is a better diagnostic tool over AFB microscopy in case detection of leprosy. From the findings we concluded that RLEP-PCR could be used for the definitive detection of leprosy cases in accordance with the clinical findings in the field condition in the post elimination era of leprosy.


Clarification of recombinant proteins from high cell density mammalian cell culture systems using new improved depth filters.
Increasingly high cell density, high product titer cell cultures containing mammalian cells are being used for the production of recombinant proteins. These high productivity cultures are placing a larger burden on traditional downstream clarification and purification operations due to higher product and impurity levels. Controlled flocculation and precipitation of mammalian cell culture suspensions by acidification or using polymeric flocculants have been employed to enhance clarification throughput and downstream filtration operations. While flocculation is quite effective in agglomerating cell debris and process related impurities such as (host cell) proteins and DNA, the resulting suspension is generally not easily separable solely using conventional depth filtration techniques. As a result, centrifugation is often used for clarification of cells and cell debris before filtration, which can limit process configurations and flexibility due to the investment and fixed nature of a centrifuge. To address this challenge, novel depth filter designs were designed which results in improved primary and secondary direct depth filtration of flocculated high cell density mammalian cell cultures systems feeds, thereby providing single-use clarification solution. A framework is presented here for optimizing the particle size distribution of the mammalian cell culture systems with the pore size distribution of the gradient depth filter using various pre-treatment conditions resulting in increased depth filter media utilization and improved clarification capacity. Feed conditions were optimized either by acidification or by polymer flocculation which resulted in the increased average feed particle-size and improvements in throughput with improved depth filters for several mammalian systems.


Genipin versus Ferric Chloride cross-linked unmodified Gum Arabic/Chitosan/nano-Hydroxyapatite nanocomposite hydrogels as potential scaffolds for bone regeneration.
Ferric chloride (FeCl3) and Genipin were utilized as cross-linkers to create two types of nanocomposite hydrogels through physical and covalent cross-linking methods, respectively. The hydrogels were composed of unmodified Gum Arabic (GA), Chitosan (Ch), and natural nano-Hydroxyapatite (nHA) using an acrylic acid solvent. Both the natural nHA and the FeCl3 vs. genipin cross-linked GA/Ch/nHA nano-composite hydrogels were prepared and characterized using various in vitro and in vivo analysis techniques. The use of FeCl3 and genipin cross-linkers resulted in the formation of novel hydrogels with compressive strengths of (15.43-22.20 MPa), which are comparable to those of natural cortical bone. In vivo evaluation was conducted by creating calvarial defects (6 mm) in Sprague-Dawley male rats. The results showed the formation of new, full-thickness bone at the implantation sites in all groups, as evidenced by digital planar tomography and histological staining with Hematoxylin and Eosin stain (H & E). Additionally, the use of genipin as a cross-linker positively affected the hydrogel's hydrophilicity and porosity. These findings justify further investigation into the potential of these nanocomposite hydrogels for bone regeneration applications.


Carbon nanomaterials enhance survival of Agapanthus praecox callus after cryopreservation by vitrification.
Adding exogenous compounds is an effective way to improve cell survival after cryopreservation. Carbon nanomaterials (CNMs) are novel exogenous substances with small particle size and good biocompatibility. In this work, four types of CNMs were used for the cryopreservation of Agapanthus praecox callus and their possible effects and mechanism of action were analyzed. The thermal properties of the vitrification solutions tested were detected by differential scanning calorimetry. Raman spectroscopy and transmission electron microscopy analyses were used to study the distribution of CNMs inside cells. The MDA/H2O2 contents were measured to evaluate the toxicity of CNMs to cells. Supplementation of PVS2 with various CNMs at different concentrations could enhance survival. The most effective concentration was 0.3 g/L C60, which increased survival by 159% compared to untreated controls and decreased the MDA and H2O2 contents. Single-walled carbon nanotubes (SWCNTs) and C60 entered callus cells. C60 was found only in mitochondria, whereas SWCNTs were located only around the cell walls.


Insights into the fecal microbiota of captive Iberian lynx (Lynx pardinus).
The Iberian lynx (Lynx pardinus) is an endangered species restricted to several areas of Spain and Portugal. Its low genetic diversity likely provokes immune depression and high susceptibility to infectious diseases. The intestinal microbiota is closely related to host health and nutrition. In order to contribute to the knowledge of the Iberian lynx intestinal microbiota, fecal microbiota of captive specimens from two breeding centers ("La Olivilla" and "El Acebuche"), located in Southern Spain, were studied by Denaturing Gradient Gel Electrophoresis (DGGE). Results grouped microbiota in two main clusters (I and III) which included DGGE patterns of 19 out of 36 specimens, cluster I being the most frequent in "La Olivilla" (50%) and cluster III in "El Acebuche" (55.55 %) specimens. Bacteroidetes, Firmicutes and Proteobacteria phyla were identified. Segregation of clusters I and III was attributed to different microorganism presence (Pseudomonas koreensis, Pseudomonas migulae, Carnobacterium sp., Arthrobacter, Robinsoniella peorensis and Ornithinibacillus sp.) and ability to use different carbon sources. Biolog EcoPlates® results indicate high functional diversity of fecal microbiota, it being higher in cluster III. The great impact of intestinal microbiota on host health supports the importance of its microbial composition understanding. This study is the first report of captive Iberian lynx fecal microbiota composition. [Int Microbiol 20(1): 31-41 (2017)].


Volsurf computational method applied to the prediction of stability of thermostable enzymes.
A computational model for the quantitative prediction of protein thermostability has been developed by means of the Volsurf method. A data set of 22 enzymes of reported thermostability in water systems, for the most part coming from thermophilic and hyperthermophilic organisms, has been built up. Molecular descriptors of the protein surface have been calculated and their role in the stabilization of the macromolecule has been analyzed by a multivariate statistical approach. The resulting regression model has shown a good predictivity and it has been able to quantitatively identify some structural requirements correlated with protein stability. The method can be the basis for a new computational support tool in rational protein design, which is complementary to the existing methods based on the sequence analysis.


Endothelial and vascular dysfunctions and insulin resistance in rats fed a high-fat, high-sucrose diet.
This study was designed to examine the effects of a high-fat, high-sucrose (HFHS) diet on vascular and metabolic actions of insulin. Male rats were randomized to receive an HFHS or regular chow diet for 4 wk. In a first series of experiments, the rats had pulsed Doppler flow probes and intravascular catheters implanted to measure blood pressure, heart rate, and regional blood flows. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine skeletal muscle glucose transport activity and to determine in vitro vascular reactivity, endothelial nitric oxide synthase (eNOS) protein expression in muscle and vascular tissues and endothelin content, nitrotyrosine formation, and NAD(P)H oxidase protein expression in vascular tissues. The HFHS-fed rats displayed insulin resistance, hyperinsulinemia, hypertriglyceridemia, hyperlipidemia, elevated blood pressure, and impaired insulin-mediated renal and skeletal muscle vasodilator responses. A reduction in endothelium-dependent vasorelaxation, accompanied by a decreased eNOS protein expression in muscles and blood vessel endothelium, and increased vascular endothelin-1 protein content were also noted in HFHS-fed rats compared with control rats. Furthermore, the HFHS diet induced a reduced insulin-stimulated glucose transport activity in muscles and increased levels of NAD(P)H oxidase protein and nitrotyrosine formation in vascular tissues. These findings support the importance of eNOS protein in linking metabolic and vascular disease and indicate the ability of a Westernized diet to induce endothelial dysfunction and to alter metabolic and vascular homeostasis.


When does NICE recommend the use of health technologies within a programme of evidence development? : a systematic review of NICE guidance.
There is growing interest internationally in linking reimbursement decisions with recommendations for further research. In the UK, the National Institute for Health and Clinical Excellence (NICE) can issue guidance to approve the routine use of a health intervention, reject routine use or recommend use within a research programme. These latter recommendations have restricted use to 'only in research' (OIR) or have recommended further research alongside routine use ('approval with research' or AWR). However, it is not currently clear when such recommendations are likely to be made. This study aims to identify NICE technology appraisals where OIR or AWR recommendations were made and to examine the key considerations that led to those decisions. Draft and final guidance including OIR/AWR recommendations were identified. The documents were reviewed to establish the characteristics of the technology appraisal, the cost effectiveness of the technologies, the key considerations that led to the recommendations and the types of research required. In total, 29 final and 31 draft guidance documents included OIR/AWR recommendations up to January 2010. Overall, 86 % of final guidance included OIR recommendations. Of these, the majority were for technologies considered to be cost ineffective (83 %) and the majority of final guidance (66 %) specified the need for further evidence on relative effectiveness. The use of OIR/AWR recommendations is decreasing over time and they have rarely been used in appraisals conducted through the single technology appraisal process. NICE has used its ability to recommend technologies within research programmes, although predominantly within the multiple technology appraisal process. OIR recommendations have been most frequently issued for technologies considered cost ineffective and the most frequently cited consideration is uncertainty related to relative effectiveness. Key considerations cited for most AWR recommendations and some OIR recommendations included a need for further evidence on long-term outcomes and adverse effects of treatment.


Anorexia nervosa and bulimia nervosa in children and adolescents: a review of the past 10 years.
To critically review the research in juvenile anorexia nervosa and bulimia nervosa over the past 10 years and highlight recent advances in normal development as it pertains to these disorders and their diagnosis, prevention, and treatment. Computerized search methods were combined with manual searches of the literature. A detailed review of the most salient articles is provided. Preference was given to studies involving children and adolescents that approached the subject from a developmental perspective. The information from these studies is presented in a developmental framework. Research in eating disorders has progressed, but definitive longitudinal data are still absent from the literature. Research specific to treatment of child and adolescent eating disorders remains rare. Data approaching eating disorders from a developmental perspective are available in only a few studies. Research is needed addressing normative data on the development of eating behavior and specific risk and resilience factors for pathology in specific developmental periods. Especially lacking are studies regarding the continuities and discontinuities of eating disturbances across the life span. Best documented are epidemiological studies of prevalence and incidence, long-term outcome in anorexia nervosa, and short-term treatment response in bulimia.


Investigation of the anti-cancer effect of quercetin on HepG2 cells in vivo.
Quercetin, a natural polyphenolic flavonoid compound, can inhibit the growth of several malignant cancers. However, the mechanism still remains unclear. Our previous findings have suggested that quercetin can significantly inhibit HepG2 cell proliferation and induce cell apoptosis in vitro. It can also affect cell cycle distribution and significantly decrease cyclin D1 expression. In this study, we investigated the anti-cancer effect of quercetin on HepG2 tumor-bearing nude mice and its effect on cyclin D1 expression in the tumor tissue. First, the nude murine tumor model was established by subcutaneous inoculation of HepG2 cells, then quercetin was administered intraperitoneally, and the mice injected with saline solution were used as controls. The daily behavior of the tumor-bearing mice was observed and differences in tumor growth and survival rate were monitored. The expression of cyclin D1 in isolated tumor sections was evaluated by immunohistochemistry. We found that HepG2 tumor became palpable in the mice one-week post-inoculation. Tumors in the control group grew rapidly and the daily behavior of the mice changed significantly, including listlessness, poor feeding and ataxia. The mice in quercetin-treated group showed delayed tumor growth, no significant changes in daily behavior, and the survival rate was significantly improved. Finally, we observed increased tumor necrosis and a lighter cyclin D1 staining with reduced staining areas. Our findings thus suggest that quercetin can significantly inhibit HepG2 cell proliferation, and this effect may be achieved through the regulation of cyclin D1 expression.


Pharmacokinetics and pharmacodynamics of nifedipine in pregnant sheep.
The calcium channel blocker nifedipine was administered to pregnant sheep by a four-level iv infusion at rates of 1-10 micrograms/kg/min. The maternal and fetal plasma nifedipine concentrations were measured along with maternal and fetal heart rate, blood pressure, pH, and blood gases. The two-compartment maternal pharmacokinetics demonstrated a rapid phase t1/2 of 11 min and a slower phase t 1/2 of 137 min. The drug reached the fetus via a first-order process with a t 1/2 of 22 min. At the highest dose, the maternal systemic vascular resistance dropped 49% in association with a 59% increase in heart rate. The uterine blood flow decreased 29%. Tachycardia was the only significant effect in the fetus. In a subgroup of sheep, chronic dosing with phenobarbital increased maternal nifedipine clearance 3-fold.


Design and Implementation of a Novel Double-Layered Wavy Mattress for the Prevention and Recovery of Pressure Ulcers: A Feasibility Study.
Pressure ulcers are a significant concern in patient care, particularly for those with limited mobility and extended hospital stays. Wavy mattresses are shown an effective tool for preventing or promoting the healing of these wounds by preventing pressure localization in different body regions. The current study aimed to present a novel double-layered wavy mattress design for the prevention and recovery of pressure ulcers, addressing some of the limitations of existing mattresses. The novel mattress includes double-layered cells, with the upper and lower layers, filled with water and air, respectively. The temperature of water in the cells can be manually adjusted to meet patients' needs, prevent skin sweating, regulate body temperature, and promote blood flow in areas susceptible to pressure ulcers. Patients who used this novel mattress during their hospitalization experienced a significantly shorter recovery period for bedsores compared to those who used other mattresses, showing that the novel wavy mattress is an effective tool for preventing and recovering from pressure ulcers in long-term hospitalized patients with limited mobility.


Electrical characteristics and doping mechanism of DNA molecules doped with iodine solutions.
This study examined the electrical characteristics of deoxyribonucleic acid (DNA) molecules doped with iodine solution and their chemical state changes before and after doping. The experiments were progressed in each lambda (A), poly(dA)-poly(dT) and poly(dG)-poly(dC) DNA under the same conditions. The authors prepared 20 nm gap Au/Ti electrodes fabricated by e-beam lithography. DNA solutions were dropped on the nano gap of the electrodes and DNA films were formed by drying in a vacuum. DNA films were doped with an iodine solution dissolved in methanol. The authors measured the electrical conductivity of DNA molecules as the number of iodine doping times in 10(-2) torr vacuum. As increase of the iodine solution doping number, the electrical conductivity of three sorts of DNA molecules was remarkably improved respectively. X-ray photoelectron spectroscopy (XPS) was performed to inspect the electrical conduction mechanism that holes on DNA nitrogen region were generated by transferring electrons to iodine molecules.


Phase changes in Lennard-Jones mixed clusters with composition Ar(n)Xe(6-n) (n=0,1,2).
We have carried out parallel tempering Monte Carlo calculations on the binary six-atom mixed Lennard-Jones clusters, Ar(n)Xe(6-n) (n=0,1,2). We have looked at the classical configurational heat capacity C(V)(T) as a probe of phase behavior. All three clusters show a feature in the heat capacity in the region of 15-20 K. The Ar(2)Xe(4) cluster exhibits a further peak in the heat capacity near 7 K. We have also investigated dynamical properties of the Ar(2)Xe(4) cluster as a function of temperature using molecular dynamics. We report the interbasin isomerization rate and the bond fluctuation parameter obtained from these calculations. At 7 K, the isomerization rate is on the order of 0.01 ns(-1); at 20 K, the isomerization rate is greater than 10 ns(-1). Furthermore, at 7 K, the bond fluctuation parameter is less than 3%; at 20 K, it is in the range of 10-15% (depending on the sampling time used). Using this information, together with Monte Carlo quenching data, we assign the 15-20 K feature in the heat capacity to a solid-liquid phase change and the 7-K peak to a solid-solid phase change. We believe this is the smallest Lennard-Jones cluster system yet shown to exhibit solid-solid phase change behavior.


Role of cyclic GMP of canine vascular smooth muscle in relaxation by organic nitrates.
The effects of organic nitrates on tone and tissue cyclic nucleotide levels were studied, using canine coronary, mesenteric and renal arteries, and femoral veins. Glyceryl trinitrate (GTN) relaxed all vascular tissues examined and increased tissue cyclic GMP (cGMP) levels in a concentration-dependent manner, but GTN induced no significant changes in cyclic AMP (cAMP) levels. An increase in cGMP levels induced by 10 microM of GTN in coronary arteries was observed before the onset of relaxation. Methylene blue, an inhibitor of guanylate cyclase, inhibited the relaxant effect of GTN and decreased cGMP levels. In contrast, M & B 22,948, an inhibitor of cGMP phosphodiesterase, not only enhanced relaxation by GTN, but also increased cGMP levels. Other organic nitrates, pentaerythritol tetranitrate (PETN), nicorandil (NIC), and isosorbide dinitrate (ISDN), also relaxed coronary arteries and increased cGMP levels in a concentration-dependent manner. A significant correlation was observed between percentage increases in cGMP levels and percentage relaxation by 10 microM of GTN, PETN, NIC, and ISDN (r = 0.952, p less than 0.001). Plasma concentrations of 4 organic nitrates inversely correlated with percentage increases in cGMP levels by 10 microM of these agents in coronary arteries (r = -0.845, p less than 0.001). These results suggest that an increase in cGMP is responsible for relaxation in vascular smooth muscles by organic nitrates, and that therapeutic plasma concentrations may be estimated by the degree of increase in cGMP levels induced by their administration.


Stress relaxation of porcine gluteus muscle subjected to sudden transverse deformation as related to pressure sore modeling.
Computational studies of deep pressure sores (DPS) in skeletal muscles require information on viscoelastic constitutive behavior of muscles, particularly when muscles are loaded transversally as during bone-muscle interaction in sitting and lying immobilized patients. In this study, we measured transient shear moduli G(t) of fresh porcine muscles in vitro using the indentation method. We employed a custom-made pneumatic device that allowed rapid (2000 mms) 4 mm indentations. We tested 8 gluteus muscles, harvested from 5 adult pigs. Each muscle was indented transversally (perpendicularly to the direction of fibers) at 3 different sites, 7 times per site, to obtain nonpreconditioned (NPC) and preconditioned (PC) G(t) data. Short-term (GS) and long-term (GL) shear moduli were obtained directly from experiments. We further fitted measured G(t) data to a biexponential equation G(t) = G1 x exp(-t/tau1)+ G2 x exp(-t/tau2) + Ginfinity, which provided good fit, visually and in terms of the correlation coefficients. Typically, plateau of the stress relaxation curves (defined as 10% difference from final GL) was evident approximately 20 s after indentation. Short-term shear moduli GS (mean NPC: 8509 Pa, PC: 5711 Pa) were greater than long-term moduli GL (NPC: 609 Pa, PC: 807 Pa) by about an order of magnitude. Statistical analysis of parameters showed that only G2 was affected by preconditioning, while GL, GS, Ginfinity, tau1, tau2, and G1 properties were unaffected. Since DPS develop over time scales of minutes to hours, but most stress relaxation occurs within approximately 20 s, the most relevant property for computational modeling is GL (mean approximately 700 Pa), which is, conveniently, unaffected by preconditioning.


Plausible mechanism of melamine-related urinary calculi formation in children: a model description.
To explore melamine-related urinary calculi (MRUC) formation mechanism. Twenty-four MRUC and 19 adult urinary stones (serving as controls) were included. Stone calcium, uric acid, creatinine, creatine, melamine, and cyanuric acid levels were measured quantitatively using flame atomic absorption spectrum and high-performance liquid chromatography, respectively. The structure of extractions from MRUC and controls, artificial melamine-cyanurate assemblies, chromatographic-grade uric acid, creatine, and creatinine were investigated by transmission electron microscope. Creatinine and creatine levels in MRUC were significant higher than those in controls (P = .000., 008). There were positive correlations between MRUC creatinine level and creatine and uric acid levels (r = .854, 0.846, P = .002, 001). However, no relationship was found between MRUC-children's blood biochemical indexes and stone indexes (P > .05). Compared with noncalcium oxalate-containing MRUC, calcium oxalate-containing MRUC had more melamine and cyanuric acid but without significance (P = .497). No relationship was found between MRUC calcium level and melamine and cyanurate levels (P = .481). Networks only observed in extractions from MRUC core area were very similar to those in artificial melamine-cyanurate assemblies. The single molecule size of creatine, creatinine, and uric acid was less than the mesh observed both in MRUC and artificial melamine-cyanurate assemblies. This study primarily illustrates existence of networks in MRUC. Smaller molecules in urine, especially acidic molecules, are probably trapped in the mesh within renal tubule provided by melamine-cyanurate assemblies networks based on its molecule sievelike effect and alkaline nature, which induces nucleation in MRUC formation.


A general two-step one-pot synthesis process of ynones from α-keto acids and 1-iodoalkynes.
A general two-step one-pot synthesis process of ynones was developed by cycloaddition of α-keto acids and 1-iodoalkynes followed by a ring-opening reaction. Its easy conditions and novel mechanism endowed it with two distinctive advantages: iodine-atom bonded to C(sp2) remained intact and α-keto acids became a part of the triple bonds in ynones.


Some electron microscope findings of the claustrum of the cat.
The claustrum of the cat is basically composed of 4 classes of neuron. Class I is a rather small neuron (less than 10 mu in diameter) and is provided with rather few cytoplasmic organelles, while Class IV, large (25-30 mu), neuron possesses an abundance of them. Class II, medium-sized (15-20 mu), neuron and fusiform Class III neuron (about 15 X 25 mu) exhibit an intermediate form of the former two classes. Perikaryal and proximal dendritic surface of Class IV neurons are covered with many boutons, while neurons of the other three classes have few of such terminals on their perikaryal surface. The dendritic profiles of rather reduced diameter bear a few axonal terminals. Five types of terminals are recognized: (1) Type A terminal, small in profile, with uniform sized round vesicles (about 300 A in diameter) making asymmetrical synapses; (2) Type B terminal of small size, containing round vesicles of various diameters (300-400 A) and forming asymmetrical synaptic contacts; (3) Type C, also small in profile, being filled with pleomorphic vesicles and making symmetrical synapses; (4) Type D large terminal with numerous pleomorphic vesicles, many mitochondria and a number of glycogen-like granules, forming symmetrical synapses; and (5) Type E terminal containing numerous granular vesicles (800-1,000 A). The Type C and some of Type A terminals usually synapse upon the cell bodies and proximal dendrites, while most of Type A, B, D and E make synapse upon medium to small dendritic profiles and spines. The problem whether or not the cytoarchitecture of the claustrum at the light microscope level is identifiable at the ultrastructural level as well, and the possible origin of various types of terminals above described, were discussed briefly.


Inhibition of Escherichia coli and Bacillus subtilis FtsZ Polymerization and Bacillus subtilis Growth by Dihydroxynaphtyl Aryl Ketones.
The increasing detection of virulent and/or multidrug resistant bacterial strains makes necessary the development of new antimicrobial agents acting through novel mechanisms and cellular targets. A good choice are molecules aimed to interfere with the cell division machinery or divisome, which is indispensable for bacterial survival and propagation. A key component of this machinery, and thus a good target, is FtsZ, a highly conserved GTPase protein that polymerizes in the middle of the cell on the inner face of the cytoplasmic membrane forming the Z ring, which acts as a scaffold for the recruitment of the divisome proteins at the division site. In this work, we tested the inhibitory effect of five diaryl naphtyl ketone (dNAK) molecules on the in vitro polymerization of both Escherichia coli and Bacillus subtilis FtsZ (EcFtsZ and BsFtsZ, respectively). Among these compounds, dNAK 4 showed the strongest inhibition of FtsZ polymerization in vitro, with an IC50 of 2.3 ± 0.06 μM for EcFtsZ and 9.13 ± 0.66 μM for BsFtsZ. We found that dNAK 4 binds to GDP-FtsZ polymers but not to the monomer in GTP or GDP state. This led to the polymerization of short and curved filaments, rings, open rings forming clusters, and in the case of BsFtsZ, a novel cylindrical structure of stacked open rings. In vivo, dNAK 4 had almost no effect on the growth of E. coli in liquid culture, in contrast to the strong inhibitory effect observed over B. subtilis growth. The insensitivity of E. coli to this compound is probably related to the impermeability of dNAK 4 to the outer membrane. The low amount of this compound required to inhibit several of the bacterial strains tested and the lack of a cytotoxic effect at the concentrations used, makes dNAK 4 a very good candidate as a starting molecule for the development of a new antibiotic.


The effects of melatonin in the treatment of acute brachial plexus compression injury in rats.
Brachial plexus injury (BPI) is one of the most destructive peripheral nerve injuries and there is still a lack of effective treatment. This study was conducted to evaluate the effects of melatonin in the treatment of acute brachial plexus compression injury in rats using histopathological, histomorphometric, immunohistochemical and electrophysiological methods. Forty-eight adult male Sprague Dawley rats were randomly allocated into three groups: sham, melatonin and vehicle groups. The brachial plexus compression injury model was performed by a vascular clamp. Melatonin group received intraperitoneal injection of melatonin at doses of 10 mg/kg for 21 days after crush injury. The conduction velocity and amplitude of compound muscle action potential (CAMP) in the regenerated nerve, and nerve histomorphometry, as well as levels of myelin protein zero (P0) protein of the crush region were assessed. Compared with the vehicle group, the melatonin group which reported significant increased CMAP conduction velocity and amplitude also showed thicker myelin sheath and lower levels of P0 protein. Our results suggest that melatonin effectively promotes nerve regeneration and improves the function of damaged nerves. Melatonin treatment is a promising strategy for the treatment of acute brachial plexus compression injury.


A multinational and multidisciplinary approach to treat CHD in paediatric age in Angola: initial experience of a medical-surgical centre for children with heart disease in Angola.
Epidemiological patterns of cardiac disease differ between developed countries and African nations. Despite the collaborative efforts of developed countries, several obstacles hinder the implementation of successful programmes for the management of children with heart disease in Africa. Materials and methods This study is a retrospective analysis of a bi-national two-institution partnership programme for the treatment of children with congenital and acquired heart disease. In April, 2011, a continuous medical-surgical programme was inaugurated at Clínica Girassol in Luanda. The main goals were to initiate permanent and local delivery of services while training local teams, allowing autonomous medical and surgical management of children with heart disease. Between April, 2011 and August, 2015, a total of 1766 procedures were performed on 1682 children. Of them, 1539 had CHD and 143 had acquired heart disease; 94 children underwent interventional treatment. A total of 1672 paediatric surgeries were performed on 1588 children: 1087 (65%) were performed with extracorporeal circulation and 585 (35%) were off-pump. The age distribution of the children was 4.5% (n=76) neonatal, 40.4% (n=675) between 30 days and 1 year, and 55.1% (n=921) over 1 year. There were 76 re-operations (4.5%) due to complications. The 30-day mortality rate was 4.2% (71 patients). Education-wise, several Angolan medical and surgical specialists were trained, allowing near-autonomous cardiac care delivery in children with heart disease. An innovative cooperation model between a European and an African centre based on permanent delivery of care and education allowed for effective training of local teams and treatment of children with heart disease in their own environment.


Beyond myth and magic: the future of evidence-based leadership.
Leaders must understand the essential characteristics and realities of creating an evidence-driven organization. It is especially important to comprehend and apply sound leadership and management of infrastructure, processes, and behaviors that incorporate evidence in every aspect of clinical practice. Evidence-driven practice is no longer optional and is now a fundamental leadership requisite in all clinical settings.


Newly-found functions of metformin for the prevention and treatment of age-related macular degeneration.
Metformin (MET), a first-line oral agent used to treat diabetes, exerts its function mainly by activating adenosine monophosphate-activated protein. The accumulation of oxidized phospholipids in the outer layer of the retina plays a key role in retinal pigment epithelium (RPE) cells death and the formation of choroidal neovascularization (CNV), which mean the development of age-related macular degeneration (AMD). Recent studies have shown that MET can regulate lipid metabolism, inhibit inflammation, and prohibit retinal cell death and CNV formation due to various pathological factors. Here, newly discovered functions of MET that may be used for the prevention and treatment of AMD were reviewed.


Characterization and Inception of a Triterpenoid Astrakurkurol, as a Cytotoxic Molecule on Human Hepatocellular Carcinoma Cells, Hep3B.
Mushrooms are customary influential sources of pharmaceutically active metabolites. Usually lanostane-type triterpenoids from mushrooms had prospective for cancer disease treatments. Recently, a triterpenoid, astrakurkurol obtained from the fresh basidiocarps of the edible mushroom Astraeus hygrometricus, drew attention as a new cytotoxic therapeutic. The structural stability of this triterpenoid had been established with the amalgamation of density functional theory (DFT) calculations and study of single-crystal X-ray diffraction. To successfully manifest astrakurkurol as a potent cytotoxic therapeutics, a wide apprehension on the molecular and cellular mechanisms underlying their action is prerequisite. On this account, our study was directed to scrutinize the influence of this triterpenoid on human hepatocellular cancer cell model Hep3B. Encapsulating all experimental facts revealed that astrakurkurol had significantly decreased cell viability in a concentration-dependent manner. This effect was unveiled to be apoptosis, documented by DNA fragmentation, chromatin condensation, nuclear shrinkage, membrane blebing, and imbalance of cell cycle distribution. Astrakurkurol persuaded the expression of death receptor associated proteins (Fas), which triggered caspase-8 activation following tBid cleavage. Moreover, tBid mediated ROS generation, which triggered mitochondrial dysfunction and activated the mitochondrial apoptotic events. Astrakurkurol cytotoxicity was based on caspase-8-mediated intrinsic apoptotic pathway and was associated with inhibition at Akt and NF-κB pathway. Astrakurkurol had also inhibited the migration of Hep3B cells, indicating its antimigratory potential. These findings led us to introduce astrakurkurol as a feasible and natural source for a safer cytotoxic drug against hepatocellular carcinoma.


Persistent disparities in health insurance coverage: Hispanic children, 1996 to 2005.
To identify how health insurance coverage trends changed for Hispanic children between 1996 and 2005. Data from the Current Population Survey Annual Social and Economic Supplement were analyzed to determine health insurance coverage rates for Hispanic children and logistic regression was used to determine the role of race/ethnicity on health insurance status, adjusting for citizenship status, child characteristics, migration status, and geography. The proportion of uninsured Hispanic children decreased significantly. However, the increased likelihood of a Hispanic child being uninsured relative to non-Hispanic White children did not change during this period. Expansions in public health insurance programs between 1996 and 2005 increased health insurance coverage for Hispanic children but disparities between Hispanic and non-Hispanic White children persist.


High power and high SFDR frequency conversion using sum frequency generation in KTP waveguides.
We characterize the intermodulation distortion of high power and efficient frequency conversion of modulated optical signals based on sum frequency generation (SFG) in a periodically poled potassium titanyl phosphate (KTP) waveguide. Unwanted frequency two-tone spurs are generated near the converted signal via a three-step cascaded three-wave mixing process. Computer simulations describing the process are presented along with the experimental measurements. High-conversion efficiencies and large spur-free dynamic range of the converted optical signal are demonstrated.


Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity.
Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity-including fever, viremia, and viral loads in spinal cord and testes-and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.


The broiler chicken as a model for immunotoxicity assessment. 1. Standardization of in vitro immunological assays.
The broiler chicken was developed as an alternative animal model to laboratory rodents for immunotoxicologic assessment. In vivo treatment with 100-200 mg/kg cyclophosphamide (CY) was used as a known immunosuppressive treatment to standardize the assay systems. Protocols for assessing specific immunological functions were developed in specific pathogen-free (SPF) broilers to measure lymphocyte blastogenesis to T-cell (concanavalin A and phytohemagglutinin) and B-cell (Staphylococcus aureus cells) mitogens, delayed-type hypersensitivity (DTH) to tuberculin, natural killer (NK) cell cytotoxicity, plaque-forming cell (PFC) response to sheep red blood cells (SRBC), and serum antibody titers to SRBC. CY was an effective immunosuppressant in the broiler system for assessment of lymphocyte responsiveness to mitogenic stimulation, DTH reactivity, and the antibody response to SRBC as assessed by PFC and serum antibody titers. NK cytotoxicity was not altered on a cellular level following treatment with CY at a dose that produced greater than 75% depletion of spleen cellularity. However, under these conditions, it must be assumed that the capacity of CY-treated birds to mediate NK effector functions would be reduced. These results demonstrate the applicability of the broiler chicken as an animal model for immunotoxicity testing.


Does hinge sidedness influence laterality of C5 palsy after expansile open-door cervical laminoplasty?
Cervical expansile open-door laminoplasties (EOLPs) have an open side and a hinge side, with the open side being bridged by grafts or miniplates. The authors explored the possibility that the open-door side might have a greater incidence of C5 palsy due to a greater stretch of the ipsilateral C5 nerve root. This study was a retrospective review of prospectively collected data over a period of 25 years specifically assessing surgical complications. Included were patients who underwent EOLP for myelopathy, radiculopathy, or mild central cord injuries (American Spinal Injury Association Impairment Scale [AIS] grade D). Exclusion criteria included preexisting C5 weakness; patients with AIS grade A, B, or C injury; and added instrumentation or additional surgical procedures. Patients were monitored postoperatively for C5 palsy or any other complications. A comparison group included patients who underwent cervical laminectomy and fusion (CLF). A total of 327 laminoplasties were collected, and 31 patients were excluded because of severe spinal cord injury (AIS grades A-C), 3 for preoperative C5 weakness, and 21 for instrumentation or additional surgical procedures. Thus, 272 patients were analyzed with a mean age of 59.9 years (range 22-88 years). Diagnoses at presentation were cervical myelopathy (84.1%), central cord syndrome (7.2%), cervical myeloradiculopathy (3.4%), ossification of the posterior longitudinal ligament (1.9%), and other (3.4%). The most common complications were C5 palsy (n = 7, 2.6%) and wound infection (n = 7, 2.6%). Of the 7 cases of postoperative C5 palsies in this study, 6 occurred on the side of the open door. Of the C5 palsies, 2 were mild, 3 were moderate, and 2 were severe. Two of the 7 C5 palsies had a delayed (> 24 hours) onset. The C5 palsy incidence after CLF was 2.7% with no side preference. C5 palsy after cervical decompression for myelopathy is a known occurrence, with a rate of 2.6% in the current study. The authors found that C5 palsies more commonly occur on the open side of the laminoplasty. This could be due to a greater manipulation of the nerve root on the side of the open door or greater stretch of the C5 root on the open-door side. If clinical symptoms and anatomical stenosis are symmetric, the authors recommend creating the laminoplasty hinge on the patient's dominant side to minimize potential loss of dominant proximal arm function.


Anti-hepatitis B immunoglobulin for clinical use.
Anti-hepatitis B immunoglobulin, prepared by a method which involves the initial removal of the fibrinogen fraction, has been reported to lack certain antibodies and fail to detect certain hepatitis B surface antigens when used as a detector reagent in counter-immunoelectrophoresis. The possibility exists that any passive immunity conferred by the immunoglobulin might not protect against these antigens. Anti-hepatitis B immunoglobulin prepared from plasma by a modified technique which omitted the precipitation of the fibrinogen fraction reacted against these antigens in gel precipitin tests. It is suggested that such a method is preferable for the production of anti-hepatitis B surface immunoglobulin.


Before I was an embryo, I was a pre-embryo: or was I?
Issues surrounding human embryos are poignant and profound. Should research be conducted on them? Should they be discarded? Should they be donated to infertile couples? The Warnock Report was a landmark in providing guidelines limiting experimentation on human embryos to the first 14 days after fertilization, at which time implantation of the embryo is complete and the primitive streak has appeared. However, these embryological features were not considered sufficiently distinctive to bestow upon this 14-day period a separate classification. This situation changed when, in 1986, Anne McLaren suggested the use of the terms 'pre-embryo' or 'conceptus' to designate "the entire product of the fertilized egg up to the end of the implantation stage" and the term 'embryo' for "that small part of the pre-embryo or conceptus, first distinguishable at the primitive streak stage, that later develops into the foetus." In this paper we look critically at the term 'pre-embryo', and we shall present the case for an alternative set of terms, namely, embryo-placenta and embryo-fetus. We consider this latter to be biologically-based terminology, that does not have any connotation of restricted moral value as the term pre-embryo does for some.


Sympathoadrenergic regulation of metabolism and cardiocirculation during and following running exercises of different intensity and duration.
In three different field studies running loads of 2 X 200 m and 400 m, 3 X 1000 m and 3000 m, and finally 10,000 m were performed by respective groups of sprinters, middle-, and long-distance runners. We investigated the effects of exercise on the sympathoadrenal system by determining catecholamine (CA) concentrations in the venous blood and urine [free norepinephrine (NE), epinephrine (EPI)] and the respective sulfoconjugates in plasma and various hormonal, metabolic, and cardiocirculatory parameters. Endurance-trained athletes showed a lower heart rate (HR) and plasma renin activity (PRA) at rest in comparison with the sprinters. The concentrations of the plasma CA reflected the intensity more than the duration of exercise. At rest and following recovery the ratio of free NE/EPI in plasma was markedly higher in the group of sprinters in comparison with the long-distance runners. During exercise, however, an opposite movement occurred resulting in a higher ratio in the latter group. The pre-start ratios of NE/EPI in urine were similar to those in plasma. The sports disciplines' specific differences in NE/EPI both at rest and during exercise suggest that the overall sympathetic activity, reflected by NE and EPI, is regulated in a quite differentiated pattern. The sulfoconjugated CA, however, increased less clearly after the middle- and long-distance bouts than the respective free CA which caused the ratio sulfates/free CA to decline. There were strong relations between the levels of free plasma NE and EPI and that of blood lactate which, however, rather reflects a parallelism subsequent to the highly intensive stimulation.


Effect of temperature on hybridoma cell cycle and MAb production.
The kinetics of growth and antibody formation of an anti-interleukin-2 producing hybridoma line were studied in suspension culture at temperatures ranging from 34 degrees C to 39 degrees C. Flow cytometry was used to determine the effect of temperature on the cell cycle. Maximum cell density and monoclonal antibody yield were observed at 37 degrees C. The specific monoclonal antibody production rate was approximately constant throughout each batch experiment. Lower temperatures caused cells to stay longer in the G(1)-phase of the cell cycle, but temperature had only a marginal effect on the specific antibody production rate. Arresting of cells in the G(1)-phase by means of temperature was, therefore, not suited for enhanced monoclonal antibody production. Rather, antibody production for this hybridoma was directly linked to viable cell concentration.


Sexual Activity the Night Before Exercise Does Not Affect Various Measures of Physical Exercise Performance.
The idea that sexual activity can affect athletic performance has been a matter of conjecture for the past several decades. To provide preliminary data on whether sexual activity the evening before several physical exercise performance tests affects performance the next day. Eight participants (mean age, 28 ± 5 years) underwent several physical exercise performance tests on 3 different mornings, under 3 conditions: (i) no sexual intercourse the night before the tests (control), (ii) sexual intercourse the night before the tests, and (iii) yoga the night before the tests (randomized, single-blinded). Physical work capacity, lower body muscular power (standing vertical jump), upper body strength (handgrip strength), reaction time, and upper body musculoskeletal endurance (number of push-ups completed). All participants experienced orgasm through intercourse. The more pleasurable the orgasm, the lower the systolic blood pressure (SBP) on the day after intercourse (Spearman's rho = -0.86; P = .007). For every 2% increase in the total orgasm score, SBP decreased by 1 mmHg. Intercourse lasted 13 minutes; mean heart rate (HR) and caloric expenditure ranged from 88 to 145 beats/minute and from 53 to 190 kcal, respectively. There were no significant differences in the physical working capacity that elicited an HR of 170 beats/minute, number of push-ups completed, vertical jump height, grip strength, or reaction time across the 3 conditions. Orgasm through sexual activity on the night before physical exercise may reduce SBP; however, we were unable to demonstrate a statistically significant difference in physical exercise performance in any of the 3 conditions. Zavorsky GS, Vouyoukas E, Pfaus JG. Sexual Activity the Night Before Exercise Does Not Affect Various Measures of Physical Exercise Performance. Sex Med 2019;7:235-240.


Disruption of surface-induced smectic order by periodic surface corrugations.
A Fréedericksz transition measurement is reported for a liquid crystal cell composed of surfactant-coated substrates. One substrate was locally scribed with the stylus of an atomic force microscope to create a nanoscopic grooved structure. The Fréedericksz threshold voltage was found to be smaller in the scribed region than in the unscribed region, indicating that the corrugated surface disrupts surface-induced smectic order, and that the effect grows toward the nematic-smectic-A transition temperature T(NA) in conjunction with the smectic correlation length.


A 22-watt mid-infrared optical parametric oscillator with V-shaped 3-mirror ring resonator.
We report on a ZnGeP(2)-based optical parametric oscillator (OPO) with 22 W of output power in the 3-5 µm range and a beam quality factor M(2) ≈1.4. The OPO uses a novel V-shaped 3-mirror ring resonator that allows two passes of the beams through the same nonlinear crystal. The pump is a 39 W hybrid Tm:fiber laser/Ho:YAG laser.


Echocardiographic analysis of the left ventricular function in young athletes: a focus on speckle tracking imaging.
The objectives were to assess the left ventricular (LV) structure and function in regularly trained young athletes, using 2 D conventional echocardiographic (echo) methods and speckle tracking echocardiography (STE). An observational cross-sectional study. Thirty-three footballers and 20 healthy untrained subjects were included in the study. The systolic and diastolic LV functions were evaluated by 2D conventional echo parameters, Doppler method and STE. All the found values were within the normal range. The LV End Diastolic Diameter (LVED 37.24±2.08 mm/m2) and the LV Mass index (LVMi 97.93±15.58 g/m2) were significantly higher in young athletes as compared with controls. There was no difference regarding the LV systolic function assessed by conventional echo parameters in the 2 study groups. Regarding the diastolic function, the transmitral inflow velocities ratio was significantly higher in athletes (E/A = 2.10±0.49 versus 1.64±0.26, p< 0.001) but there was no difference in the filling pressure in the 2 groups. The STE demonstrated a different pattern of LV deformation in the different groups. A significant lower LV global longitudinal strain (GLS -20.68±2.05 versus -22.99±2.32 %, p<0.001) and higher radial and circumferential strains have been found in the young athletes as compared with controls. A significant relationship between the GLS values and LVED (r= 0.299, p = 0.03) and LVMi was also reported in athletes. While conventional morphological and functional echocardiographic parameters failed to distinguish the adaptations in the athlete's heart, deformation parameters showed a different pattern of LV mechanics in young footballers versus controls.


Synthesis of novel β-cyclodextrin functionalized S, N codoped carbon dots for selective detection of testosterone.
A novel functionalized carbon dot has been synthesized by covalently linking β-cyclodextrin to the surface of N, S codoped carbon dots (β-CD-CDs). The characterization was confirmed by transmission electron microscopy, X-ray photoelectron spectroscopy, infrared spectra, ultraviolet-visible, and fluorescence emission spectra. On the basis of this carbon dot and (ferrocenylmethyl) trimethylammonium iodide (Fc+), a photo-induced electron transfer (PET) fluorescent probe system was developed to determine the concentration of testosterone in water and identify testosterone in cell by fluorescence imaging as a visible biomarker. Under the optimum condition, the fluorescent intensity of the probe system linearly responded to the concentration of testosterone from 0μM to 280μM and the limit of detection was 0.51μM. This probe system also performed well at determining testosterone in groundwater with average recoveries of testosterone ranging from 96% to 107% at spiking levels of 0.5-100μM, and the relative standard deviation remained below 13%, which provided a reliable, rapid and easy method to determine testosterone in environmental water. Furthermore, the low cytotoxicity, high anti-interference ability, and excellent biocompatibility of β-CD-CDs made this probe system successfully used in cell fluorescence imaging to monitor levels of testosterone in the cytoplasm of cells with a promising application value in medical research.


Development and validation of an improved classification and risk stratification system for carotid body tumors: Multinational collaborative cohort study.
This study aims to develop and validate a new classification system that better predicts combined risk of neurological and neurovascular complications following CBT surgery, crucial for treatment decision-making. Multinational retrospective cohort study with 199 consecutive cases. A cohort of 132 CBT cases was used to develop the new classification. To undertake external validation, assessment was made between the actual complication rate and predicted risk by the model on an independent cohort (n = 67). Univariate analyses showed statistically significant associations between developing a complication and the following factors: craniocaudal dimension, volume, Shamblin classification, and Mehanna types. In the multivariate prognostic model, only Mehanna type remained as a significant risk predictor. The risk of developing complications increases with increasing Mehanna type. We have developed and then validated a new classification and risk stratification system for CBTs, which demonstrated better prognostic power for the risk of developing neurovascular complications after surgery.


Accuracy of ultrasonography in the diagnosis of acute appendicitis.
To assess the accuracy of ultrasonography in the diagnosis of acute appendicitis. A prospective randomized study was carried in the Dept. of Radiology and Imaging, Tribhuvan University, Teaching Hospital, Maharajgunj, Kathmandu, Nepal. A total of 120 patients, who were clinically diagnosed as acute appendicitis were subjected to ultrasonography of the abdomen. A detailed ultrasonography was performed and the findings were recorded. Twenty one cases had alternate diagnosis. Ninety nine cases ultimately underwent laparotomy and the retrieved appendices were sent for histopathological examination. Intra-operative, histopathological and ultrasonographic diagnoses were then statistically analyzed. Ultrasonographic, intra-operative and histopathological findings were statistically insignificant (P0.05). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy percentage of ultrasonography in the diagnosis of acute appendicitis was 85.7%, 100%, 100%, 6.7% and 85.9% respectively. Ultrasonography has a high degree of accuracy in the diagnosis of acute appendicitis. However, the diagnosis should be considered with the diameter of appendix over 6 mm. Therefore acute appendicitis with diameter of appendix having less than 6 mm should be evaluated with other diagnostic parameters.


Jugular venography for evaluation of abnormalities of the skull base.
Jugular venography done to evaluate abnormalities at the base of the skull demonstrated three distinctly different patterns depending on whether there is occlusion, invasion, or growth with in the internal jugular vein. Improper technique results in a lack of intracranial dural sinus filling which may masquerade as venous occlusion. This problem is avoided by adequate neck compression along with proper volume and rate of delivery of contrast. Radiographically, an abnormal jugular vein at the base of the skull will show a concave defect in true occlusion, constriction or invasion of the vein by tumor, or tumor growth within the vein.


Epidemiological analysis of eosinophilia and elevation of immunoglobulin E as a predictable and relative risk of enteroparasitosis.
among the intestinal parasites, the helminthiasis occupies a prominent position in Brazil, since it worsens malnutrition and the gives rise to neurovegetative disorders. Helminths like Ascaris lumbricoides, Enterobius vermicularis, hookworm, Trichuris trichiura and Strongyloides stercoralis stand out due to several factors that modulate the immune response of individuals. Among the protozoa are Giardia lamblia, Entamoeba histolytica. E. dispar. Parasitic helminth antigens are important to stimulate the production of cytokines such as interleukin-4 and interleukin-5, which act through the induction of IgE synthesis and activation of eosinophils. Eosinophilia is usually detectable in pre-patent period of parasitism, initially linked to B lymphocytes, under the command of Th-2 lymphokines (IL-4 and IL-5), producing IgE in response to initial exposure to an antigen or allergen. Serum IgE high levels occur in tissue migration of larvae or harboring of parasites in tissues. to determine the presence of eosinophils and IgE elevation in children with intestinal parasites. high levels of IgE and eosinophils were observed in groups infected and not infected (allergic) to calculate the relative risk of intestinal parasites presumptive differentiated between protozoa and helminths and check what values of these indicators are observed in the epidemiological profile of the surveyed population. the values obtained by calculating the relative risk for eosinophilia, compared with helminths and allergies was 11.71, but when examined by giardiasis compared with other diseases, the relative risk was 0.75. Since the comparison of helminths and giradiase, the relative risk was 27.33. Since IgE and its parameters were appropriate commit Helminth relative risk 0.39; Giardiasis had relative risk 8, 18 and Helminths compared with giardiasis had 0.03. in this study it was possible to observe that helminthiasis is connected with cases of eosinophilia with alteration of IgE, which in turn contributes to the presence of IgE eosionofilia and has an effector response against helminths that provides the expulsion of its larvae.


Studies on the accessory reproductive organs in the drake.
The effects of androgen on the ejaculatory groove region (EGA) of the drake were investigated. Testosterone propionate was injected into the juvenile male duckling and prepuberal castrate male. The EGR developed as a result of androgen administration, showed the characteristic appearance of EGR of adult drakes. The oozing of the fluid from the ejaculatory groove region (EGR-fluid) was observed 9 to 12 days after injection and the characteristics of the fluid were similar to those of normal drakes. Some secondary sexual organs, that is, the penis, vas deferens and vascular body were also developed by androgen injection to the same extent as those of normal drakes. Castration of adult drakes resulted in the involution of the secondary sexual organs including the EGR and the volume of EGR-fluid decreased with the lapse of days and no oozing of the fluid was observed one month after castration. In view of these results and the function of EGR, the EGR should be considered an accessory reproductive organ of the drake.


Adrenergic mechanism in circadian elevation of intraocular pressure in rabbits.
Stimulation of the ocular sympathetic nerves is essential for the circadian elevation of intraocular pressure (IOP) in rabbits. Adrenergic mechanisms that participate in this elevation of IOP around the onset of darkness were investigated using selective adrenergic agents. Unilateral topical administration of 0.0001-0.1% prazosin, an alpha-1-adrenergic antagonist, at the onset of darkness caused a dose-dependent reduction of IOP elevation. After treatment with 0.1% prazosin, the concentration of norepinephrine (NE) in aqueous humor was not changed, but the aqueous humor protein concentration was reduced. The increase of aqueous flow, determined by fluorophotometry, after the onset of darkness was not affected by 0.1% prazosin treatment. Treatment of rauwolscine, an alpha-2-adrenergic antagonist, or timolol, a beta-adrenergic antagonist, was ineffective in reducing the circadian elevation of IOP. Apraclonidine, an alpha-2-adrenergic agonist, with concentrations of 0.0001-1% caused a dose-dependent reduction of IOP elevation. Treatment with 1% apraclonidine caused a 70% reduction of aqueous humor NE, a significant attenuation of the increase of aqueous flow, and no change of aqueous humor protein concentration. These results suggest that both an increase of aqueous outflow resistance (by alpha-1-adrenergic receptors) and an increase of aqueous flow (not exclusively by beta-adrenergic receptors) contribute to the circadian elevation of IOP. Prejunctional alpha-2-adrenergic receptors may serve as an autoregulating mechanism to limit the excess release of NE and hypertensive spike in IOP.


Three-surface model for the ray tracing of an imaging acousto-optic tunable filter.
A three-surface model is proposed for the ray tracing of an imaging acousto-optic tunable filter (AOTF) in the optical design of an AOTF imaging system. The first and last surfaces are two refractive planes corresponding to the incident and exit facets of the AOTF, while the property of the second surface is defined particularly to describe the change of the ray trace owing to the interaction of the acoustic and optic waves. One parameter, the acoustic angle, is first corrected using the test tuning relation to compensate for the nonideality of the acoustic wave. The model has been verified with a two-piezotransducer AOTF to show its usefulness. The differences between the measured diffracted angles and the modeling value are below 0.01°. The comparison demonstrates the accuracy and the efficiency of the three-surface model.


Synthesis and antimicrobial activity of clindamycin analogues: pirlimycin, 1,2 a potent antibacterial agent.
The preparation of a series of analogues of clindamycin is described in which the naturally occurring five-membered cyclic amino acid amide portion of the molecule is replaced by a four-, six-, or seven-membered cyclic amino acid amide. The most interesting compound is pirlimycin (7e, U-57,930E), in which the (2S-trans)-4-n-propylhygramide portion of clindamycin is replaced by (2S-cis)-4-ethylpipecolamide. This structural modification results in significantly favorable changes in toxicity, metabolism, and antibacterial potency. Although the in vitro antibacterial activity of clindamycin and pirlimycin are nearly identical, the latter compound is 2-20 times more active than clindamycin when administered to mice experimentally infected with strains of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Bacteroides fragilis, and Plasmodium berghei. Pirlimycin is absorbed in rats and mice following both subcutaneous and oral administration. It readily penetrates B. fragilis induced abscesses in mice and is sequestered within these abscesses. A drug concentration of at least 60 times the required inhibitory concentration is maintained for 6 h following a single subcutaneous dose of 200 mg/kg. Urinary excretion of total bioactivity consists only of intact pirlimycin with no other antibacterially active metabolites being detected. Pirlimycin is tolerated well in rats and mice at the administered levels.


Take a chance on nursing mentorships. Enhance leadership with this win-win strategy.
Mentoring in nursing traditionally occurs at the master's or doctoral level, but the mutual career enhancement gained by such an alliance can be experienced at all stages of a nursing career. This article presents e-mail examples to illustrate antecedent relationship factors and the progression of phases in a mentorship between a clinically experienced RN and a doctorally prepared nursing professor. Application of this concept from a business model reveals parallels to nursing and blends perspectives from both disciplines. Also discussed are perceptual and tangible outcomes of mentorships and strategies to foster this positive approach.


Screening for PTSD in a substance abuse sample: psychometric properties of a modified version of the PTSD Symptom Scale Self-Report. Posttraumatic stress disorder.
The high rate of posttraumatic stress disorder (PTSD) among substance use disorder (SUD) patients has been documented in research protocols, but there is evidence that it is markedly under-diagnosed in clinical settings. To address the need for a brief self-report measure to identify SUD patients who may benefit from further assessment and/or treatment for PTSD, the psychometric properties of a modified version of the PTSD Symptom Scale Self-Report (PSS-SR) were examined in a treatment-seeking SUD sample (N = 118). The modified version of the PSS-SR, which measures both frequency and severity of PTSD symptoms, demonstrated good internal consistency reliability and was correlated with other self-report measures of trauma-related symptomatology. Comparisons between a structured PTSD diagnostic interview and the modified PSS-SR indicated that 89% of the PTSD positive patients were correctly classified by the modified PSS-SR. The clinical relevance of these findings was discussed.


Keratosis punctata of the palmar creases.
Nineteen cases of keratosis punctata of the palmar creases are presented. This entity, currently regarded as a variant of keratosis punctata of the palms and soles, is seen almost exclusively in blacks. It is benign, mostly asymptomatic, and sometimes familial without any sex predilection. The clinical lesions are pits and keratotic papules confined to the creases of the palms and volar surfaces of the fingers. The soles are rarely affected but a new finding reported here is the involvement of the side of feet in eight of the nineteen cases.


Improving air quality in megacities: Mexico City case study.
The development and effective implementation of solutions to the air pollution problems in the Mexico City Metropolitan Area is essential to guarantee the health and welfare of its inhabitants. To achieve this, it is essential to have the active and informed participation of the civil society, the academic community, the private sector, and the government, because dealing with pollution requires the use of different strategies in multiple fields of action. The Mexico City case study brings together health, transportation, administration, and many other interdisciplinary approaches to understanding and defeating air pollution. Although focused on the Mexico City area, the work conducted under this case study has significance for developing nations generally. Although policies to reduce air pollution should be based on the best available scientific knowledge, political will and capacity must transform this knowledge into action. This case study has developed a series of recommendations emphasizing the interaction between different disciplines that have provided the foundation for the 10-year air quality management program prepared by the Mexican Metropolitan Environmental Commission.