Development of Visually Improved Loop Mediated Isothermal Amplification for the Diagnosis of Plasmodium vivax Malaria in a Tertiary Hospital in Chandigarh, North India.
More than 80% of the global burden of the Plasmodium vivax is contributed by mainly three countries (India, Indonesia, and Pakistan). Reports from last decades have highlighted the occurrence of severe P. vivax malaria which was earlier considered to be benign. The recent trends of increasing P. vivax-associated morbidity and mortality emphasizes the need for early and accurate diagnosis of P. vivax malaria for the timely management of patients. Microscopy is considered a gold standard but needs experienced laboratory technologists. Over the last few years, Polymerase chain reaction (PCR) is being used as a highly sensitive and specific test but it requires expensive equipment which limits its use in the field. Therefore, in the present study, utility of visually improved loop-mediated isothermal amplification (LAMP) for the detection of P. vivax was evaluated targeting 18SrRNA gene in 145 microscopically confirmed P. vivax and 20 P. vivax negative patients. Sensitivity and specificity of LAMP was assessed with respect to microscopy and multiplex nested PCR (nPCR). Results of the LAMP assay was also correlated with rapid diagnostic test, multiplex nPCR and real-time PCR results. Overall, sensitivity and specificity of P. vivax-specific LAMP compared with microscopy were found to be 100% and 85%, respectively. Furthermore, detection limit for LAMP was found to be 0.8 copies/μL and it was also able to detect three complicated cases of P. vivax which were missed by microscopy. This study showed a LAMP assay to be a rapid and very sensitive method for the early diagnosis of both complicated and uncomplicated P. vivax malaria.


Clinical Evaluation of Color Doppler Ultrasound in Selecting the Optimal Treatment Modality for Infantile Hemangioma.
Objective We investigated the efficacy and safety of 1064 nm Nd: YAG laser, intense pulsed light (IPL), and lauromacrogol injection in the treatment of hemangioma, in order to evaluate the value of color Doppler ultrasound guidance in choosing the optimal treatment modality. Methods Infantile patients who were clinical diagnosed as hemangiomas were randomly divided into group A, who had color Doppler ultrasound examinations before the treatment, and group B who had the treatment without ultrasound evaluation. Patients in the group A were assigned into subgroups according to the depth of lesion by sonography: group A-1 for those who had a lesion depth <1.2 mm, and took intense pulsed light therapy; group A-2 for those who had a lesion depth ≥1.2mm and < 3 mm, and took long pulse 1064 nm Nd:YAG laser therapy; group A-3 for those who had a lesion depth ≥3mm and <5 mm, and were treated by IPL combined with long pulse 1064 nm Nd:YAG laser treatment; Group A-4 for those who had a lesion depth ≥5 mm, and took lauromacrogol injection therapy. Patients in the group B took long pulse 1064 nm Nd:YAG laser treatment without preoperative ultrasound evaluation. The efficacy and adverse reactions of the treatments between the groups were evaluated and compared statistically.Results Totally 113 patients with 128 skin lesions were enrolled in this study, 85 in the group A (mean age 6.8±7.9 months) and 28 in the group B (mean age 6.9±9.9 months). The mean depth of hemangioma was 3.3±1.1 mm in the group A, ranging from 0.5-7.8 mm, with 0.8±0.4 mm, 2.2±0.4 mm, 4.2±0.6 mm and 6.2±0.7 mm in group A1, A2, A3 and A4, respectively. The cure rates and effective rates in the group A were significantly higher than those in the group B (cure rates: 64.5% vs 56.3%, U=3.378, P=0.045; effective rates: 89.5% vs 78.1%, U=4.163, P=0.041). The adverse effect rates of the group A (vesicle 20.0%, pigmentation 46.9%, scarring 17.7%) were lower than those of the group B (vesicle 21.9%, pigmentation 60.4%, scarring 25.0%). Incidences of pigmentation and scarring were statistically significantly different (U=3.884, P=0.034, and U=4.016, P=0.032 respectively) between the two groups.Conclusion With the guidance of color Doppler ultrasound, the efficacy and safety of long pulse 1064 nmNd:YAG laser, intense pulsed light, and lauromacrogol injection in the treatment of infantile hemangioma have better outcomes compared to laser treatment alone without preoperative ultrasound examination.


Preserving the topological properties of complex networks in network sampling.
Extremely large-scale networks have received increasing attention in recent years. The development of big data and network science provides an unprecedented opportunity for research on these networks. However, it is difficult to perform analysis directly on numerous real networks due to their large size. A solution is to sample a subnetwork instead for detailed research. Unfortunately, the properties of the subnetworks could be substantially different from those of the original networks. In this context, a comprehensive understanding of the sampling methods would be crucial for network-based big data analysis. In our work, we find that the sampling deviation is the collective effect of both the network heterogeneity and the biases caused by the sampling methods themselves. Here, we study the widely used random node sampling (RNS), breadth-first search, and a hybrid method that falls between these two. We empirically and analytically investigate the differences in topological properties between the sampled network and the original network under these sampling methods. Empirically, the hybrid method has the advantage of preserving structural properties in most cases, which suggests that this method performs better with no additional information needed. However, not all the biases caused by sampling methods follow the same pattern. For instance, properties, such as link density, are better preserved by RNS. Finally, models are constructed to explain the biases concerning the size of giant connected components and link density analytically.


Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance.
γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance.


Clinical aspects of the immediate pigment darkening (IPD) reaction in normal individuals.
In order to investigate the clinical characteristics of the immediate pigment darkening (IPD) reaction for normal healthy Caucasian individuals and its conceivable relation to age, sex, skin type and to the minimal erythema dose (MED), a standardized light testing procedure was used and 72 subjects were studied. Skin type III was the most common, being found in 78% of the individuals; skin types II and IV were less common, found in only 12.5% and 9.5% respectively. Skin type I was not observed at all. Individuals with skin type II were found to have a significantly lower mean MED than those with skin types III and IV, and the IPD threshold dose was 9.0 J/cm2 or more, which was significantly more than for skin types III and IV. The IPD reaction was absent in several individuals with skin type II under the experimental conditions used. Some differences were observed concerning the mean MED and IPD threshold doses between skin types III and IV but they were not statistically significant. Age or sex did not appear to be significantly related to the MED and IPD threshold doses observed, and, furthermore, no significant correlation, either positive or negative, was found between the MED and the IPD threshold doses when investigated for individuals with skin type III.


Interventional Optical Imaging Permits Instant Visualization of Pathological Zones of Ablated Tumor Periphery and Residual Tumor Detection.
Optical imaging (OI) provides real-time clinical imaging capability and simultaneous molecular, morphological, and functional information of disease processes. In this study, we present a new interventional OI technique, which enables in vivo visualization of three distinct pathologic zones of ablated tumor periphery for immediate detection of residual tumors during a radiofrequency ablation (RFA) session. Rabbits with orthotopic hepatic tumors were divided into two groups (n = 8/group): incomplete RFA and complete RFA. Indocyanine green-based interventional OI was used to differentiate three pathological zones: ablated tumor, transition margin, and residual tumor or surrounding normal liver-with quantitative comparison of signal-to-background ratios among the three zones and between incompletely and completely ablated tumors. Subsequent ex vivo OI and pathologic correlation were performed to confirm the findings of interventional OI. Interventional OI could differentiate incompletely or completely ablated tumor peripheries, thus permitting identification of residual tumor. This technique may open new avenues for immediate assessment of tumor eradication during a single interventional ablation session. SIGNIFICANCE: Interventional optical imaging can instantly visualize pathologic zones of ablated tumor peripheries to detect residual tumors, which could revolutionize current image-guided interventional oncologic ablation techniques.


Energy landscape of social balance.
We model a close-knit community of friends and enemies as a fully connected network with positive and negative signs on its edges. Theories from social psychology suggest that certain sign patterns are more stable than others. This notion of social "balance" allows us to define an energy landscape for such networks. Its structure is complex: numerical experiments reveal a landscape dimpled with local minima of widely varying energy levels. We derive rigorous bounds on the energies of these local minima and prove that they have a modular structure that can be used to classify them.


Quercetin attenuates neuronal cells damage in a middle cerebral artery occlusion animal model.
Cerebral ischemia is a neurological disorder with high mortality. Quercetin is a flavonoid compound that is abundant in vegetables and fruits. It exerts anti-inflammatory and anti-apoptotic effects. This study investigated the neuroprotective effects of quercetin in focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) to induce focal cerebral ischemia. Quercetin or vehicle was injected 30 min before the onset of ischemia. A neurological function test, brain edema measurement, and 2,3,5-triphenyltetrazolium chloride staining were performed to elucidate the neuroprotective effects of quercetin. Western blot analysis was performed to observe caspase-3 and poly ADP-ribose polymerase (PARP) protein expression. MCAO leads to severe neuronal deficits and increases brain edema and infarct volume. However, quercetin administration attenuated the MCAO-induced neuronal deficits and neuronal degeneration. We observed increases in caspase-3 and PARP protein levels in MCAO-operated animals injected with vehicle, whereas quercetin administration attenuated these increases in MCAO injury. This study reveals the neuroprotective effect of quercetin in an MCAO-induced animal model and demonstrates the regulation of caspase-3 and PARP expression by quercetin treatment. These results suggest that quercetin exerts a neuroprotective effect through preventing the MCAO-induced activation of apoptotic pathways affecting caspase-3 and PARP expression.


Study of the Kinetics of Radiation Damage in CeO2 Ceramics upon Irradiation with Heavy Ions.
In this work, the effect of irradiation with heavy Kr15+ and Xe22+ ions on the change in the structural and strength properties of CeO2 microstructural ceramics, which is one of the candidates for inert matrix materials for dispersed nuclear fuel, is considered. Irradiation with heavy Kr15+ and Xe22+ ions was chosen to determine the possibility of simulation of radiation damage comparable to the action of fission fragments, as well as neutron radiation, considering damage accumulation at a given depth of the near-surface layer. During the research, it was found that the main changes in the structural properties with an increase in the irradiation fluence are associated with the crystal lattice deformation distortions and the consequent radiation damage accumulation in the surface layer, and its swelling. Evaluation of the effect of gaseous swelling caused by the radiation damage accumulation showed that a variation in the ion type during irradiation results in a growth in the value of swelling and destruction of the near-surface layer with the accumulation of deformation distortions. Results of the strength variation demonstrated that the most intense decrease in the near-surface layer hardness is observed when the fluence reaches more than 1013-1014 ion/cm2, which is typical for the effect of overlapping radiation damage in the material.


Effects of reduced ambient temperature on fat utilization during submaximal exercise.
The influence of cold air exposure on fuel utilization during prolonged cycle exercise was investigated. Nine male subjects cycled for 90 min in ambient temperatures of -10 degrees C, 0 degrees C, 10 degrees C, and 20 degrees C. External work performed between conditions was constant. Mean oxygen consumption (VO2) over the 90 min in the 20 degrees C trial corresponded to 64 +/- 5.8% VO2peak. Although mean skin temperature was different between trials (P < 0.05), rectal temperatures were not different. At -10 degrees C and 0 degrees C, the respiratory exchange ratio was higher compared with 10 degrees C and 20 degrees C (0.98 +/- 0.01 and 0.97 +/- 0.01 vs 0.92 +/- 0.01 and 0.91 +/- 0.01; P < 0.05). The associated rates of fat oxidation were lower at -10 degrees C and 0 degrees C compared with 10 degrees C and 20 degrees C (0.15 +/- 0.06 and 0.17 +/- 0.06 vs 0.35 +/- 0.06 and 0.40 +/- 0.04 g.min-1; P < 0.05). Blood glycerol was lower at -10 degrees C and 0 degrees C compared with 20 degrees C (P < 0.05); mean values were 0.13 +/- 0.0, 0.13 +/- 0.0, and 0.18 +/- 0.0 mmol.L-1 for the -10 degrees C, 0 degrees C, and 20 degrees C trials, respectively. Mean VO2 was lower in the -10 degrees C trial than the 20 degrees C trial (2.53 +/- 0.06 vs 2.77 +/- 0.09. L.min-1; P < 0.05). Mean blood glucose concentrations were lower at -10 degrees C than 20 degrees C (4.9 +/- 0.2 vs 5.3 +/- 0.1 mmol.L-1; P < 0.05). Although plasma epinephrine concentrations were greater during the 20 degrees C trial compared with all other trials (P < 0.05), plasma norepinephrine did not differ between trials. The diminished fat oxidation at colder temperatures potentially reflects a reduction in lipolysis and/or mobilization of FFA or impairment in the oxidative capacity of the muscle.


Screening for gastric cancer: the usefulness of endoscopy.
Gastric cancer screening is common in countries with high prevalence rates of gastric cancer. However, data supporting the effectiveness of gastric cancer screening are lacking. Thus, the aim of this review was to examine the current evidence on gastric cancer screening. Herein, we reviewed radiographic and endoscopic tests as methods of gastric cancer screening. Previous cohort studies and case-control studies have demonstrated reduced gastric cancer mortality in study populations that had undergone gastric cancer screening with radiographic tests. Recently, a case-control study in Japan reported a 30% reduction in gastric cancer mortality when screening was undertaken via endoscopy. Also, endoscopic screening for gastric cancer exhibited higher sensitivity and specificity than radiographic screening. Moreover, most cost-effectiveness analyses on the best strategy for detecting early gastric cancer have generally concluded that endoscopy is more cost-effective than radiographic testing. Although data on the impact of endoscopy screening programs on gastric cancer mortality are limited, recent study results suggest that gastric cancer screening by endoscopy in average-risk populations performs better than radiography screening. Further evaluation of the impact of these screening methods should take into account cost and any associated reduction in gastric cancer mortality.


Silicon (Si) alleviates cotton (Gossypium hirsutum L.) from zinc (Zn) toxicity stress by limiting Zn uptake and oxidative damage.
Silicon (Si) is as an important fertilizer element, which has been found effective in enhancing plant tolerance to variety of biotic and a-biotic stresses. This study investigates the Si potential to alleviate zinc (Zn) toxicity stress in cotton (Gossypium hirsutum L.). Cotton plants were grown in hydroponics and exposed to different Zn concentration, 0, 25, and 50 μM, alone and/or in combination with 1 mM Si. Incremental Zn concentration in growth media instigated the cellular oxidative damage that was evident from elevated levels of hydrogen peroxide (H2O2), electrolyte leakage, and malondialdehyde (MDA) and consequently inhibited cotton growth, biomass, chlorophyll pigments, and photosynthetic process. Application of Si significantly suppressed Zn accumulation in various plant parts, i.e., roots, stems, and leaves and thus promoted biomass, photosynthetic, growth parameters, and antioxidant enzymes activity of Zn-stressed as well unstressed plants. In addition, Si reduced the MDA and H2O2 production and electrolyte leakage suggesting its role in protecting cotton plants from Zn toxicity-induced oxidative damage. Thus, the study indicated that exogenous Si application could improve growth and development of cotton crop experiencing Zn toxicity stress by limiting Zn bioavailability and oxidative damage.


Outcome of molar pregnancies in Malaysia: a tertiary centre experience.
Gestational trophoblastic disease (GTD) is a common problem among Asian ethnics. A total of 102 women with molar pregnancies between 1 January 2005 and 31 December 2010, were analysed. The aim of the study was to determine the outcome of all molar pregnancies in our institution. The local incidence of molar pregnancy was 2.6 per 1,000 deliveries. A total of 48 women (47.1%) had complete hydatidiform mole and another 54 (52.9%) had partial mole. The mean age of the women with molar pregnancies was 32.0 ± 7.9 years. The mean gestational age at initial diagnosis was 11 weeks ± 3 days. The majority (97 women, 95.1%) had symptoms of vaginal bleeding and 18 (17.6%) women had a uterus larger than dates. A total of 48 (47.1%) women had ultrasound scan findings of 'snow-storm' appearance. None of the women with uncomplicated molar pregnancy had evidence of relapse following one undetectable serum β-hCG level. Four out of the 102 women (3.9%) developed persistent trophoblastic disease before attaining one undetectable serum β-hCG level. All four women required single agent methotrexate and they remained in remission. The prognosis for uncomplicated molar pregnancy is good. Establishment of a National Trophoblastic Centre is recommended to maintain optimal outcome.


Butyric acid - a well-known molecule revisited.
The properties of butyric acid, and the role it plays in the gastrointestinal tract, have been known for many years. However, the newest research shows that butyric acid still remains a molecule with a potential that has not as yet been fully exploited. The article provides an outline of relevant up-to-date knowledge about butyric acid, and presents the expert position on the clinical benefits of using butyric acid products in the therapy of gastrointestinal diseases.


Pulmonary embolism in pregnancy: a diagnostic dilemma.
The diagnosis of PE in pregnancy poses a challenge due to pregnancy-related physiological changes. Missing the PE or wrongly treating a pregnant woman for PE has serious clinical consequences. There has been concern over the use of radiation-based imaging modalities due to risk of teratogenicity and oncogenicity. This review is focused on various diagnostic options and risks of radiation to the fetus and mother from radiation-based procedures.


Evaluating veterinary practitioner perceptions of communication skills and training.
A survey was conducted among veterinary practitioners in the UK and the USA in 2012/2013. Thematic analysis was used to identify underlying reasons behind answers to questions about the importance of communication skills and the desire to participate in postgraduate communication skills training. Lack of training among more experienced veterinary surgeons, incomplete preparation of younger practitioners and differences in ability to communicate all contribute to gaps in communication competency. Barriers to participating in further communication training include time, cost and doubts in the ability of training to provide value. To help enhance communication ability, communication skills should be assessed in veterinary school applicants, and communication skills training should be more thoroughly integrated into veterinary curricula. Continuing education/professional development in communication should be part of all postgraduate education and should be targeted to learning style preferences and communication needs and challenges through an entire career in practice.


The natural history of HIV-1 infection: staging classifications of disease.
We evaluated and compared four staging classification systems for HIV infection in a population-based cohort: (1) a staging based on prodromal clinical criteria; (2) the Walter Reed Staging Classification (WRSC); (3) the immunologic staging system (ISS), and (4) a simple staging based on oral disease and CD4+ T-cell depletion. The staging systems were applied to 386 HIV-infected men in the San Francisco Men's Health Study cohort who did not have AIDS at the baseline examination. After 48-56 months of follow-up the cumulative incidence of AIDS and the cumulative mortality by stage was determined for each staging. Unlike the other systems, the WRSC could not classify a substantial proportion of HIV-infected men (51.9%). The WRSC and ISS include one or more stages which did not appear to be associated with a prognosis substantially different from that of adjacent stages. The simplified staging system based on CD4+ T-cell depletion and oral disease may be the most effective of the systems studied. A more complete understanding of the pathophysiology during the evolution of HIV infection will be required to define a more detailed staging of this disease.


Instantiating and monitoring treatment protocols.
This paper presents a system for protocol-based treatment planning, plan execution, and execution monitoring. The approach, named SPIN, is developed as a component of the Guardian system. Guardian is an experimental architecture for intelligent patient monitoring and control. The paper describes and illustrates SPIN in a clinical scenario.


Effective noise theory for the nonlinear Schrödinger equation with disorder.
For the nonlinear Shrödinger equation with disorder it was found numerically that in some regime of the parameters Anderson localization is destroyed and subdiffusion takes place for a long time interval. It was argued that the nonlinear term acts as random noise. In the present work, the properties of this effective noise are studied numerically. Some assumptions made in earlier work were verified, and fine details were obtained. The dependence of various quantities on the localization length of the linear problem were computed. A scenario for the possible breakdown of the theory for a very long time is outlined.


Omental Free Flap Coverage for Extracavitary Vascular Bypass Graft Salvage.
Prosthetic vascular graft infection is a serious complication associated with significant morbidity and mortality often requiring graft excision and numerous additional operations. Pedicled flaps are often used for the coverage of exposed deep tissue or hardware for graft salvage. In the absence of pedicled options, the properties of omentum make it an excellent choice for free flap tissue coverage, particularly in cases involving implanted prostheses. A 63-year-old woman developed a mycotic right subclavian arterial aneurysm requiring ligation and extra-anatomic bypass grafting to restore right-sided intracranial and right upper extremity arterial perfusion. Subsequent wound breakdown and poor healing left the grafts exposed, resulting in contamination. Given the profound risks associated with graft excision in this patient, salvage was attempted with IV antibiotics, serial wound/graft washouts, and graft coverage with an omental free flap. The patient tolerated the procedure well. The remainder of her hospital course was uneventful, and she was discharged home in good clinical condition. She will remain on long-term suppressive antibiotics per Infectious Disease recommendations. Contemporary literature reporting novel and effective applications of omental free flap coverage is rare. This report demonstrates that omental free flap coverage is safe and can provide healthy tissue to protect implanted grafts and even aid in the salvage of infected extra-anatomic bypass grafts.


Non-insulinoma Pancreatogeneous Hypoglycemia Syndrome with False-Positive Somatostatin Receptor Scintigraphy: A Case Report and Review of Literature.
Non-insulinoma pancreatogeneous hypoglycemia syndrome (NIPHS) is a rare cause of hypoglycemia in adults. The cause of NIPHS is diffuse hyperinsulinism. As a result, computed tomography (CT) of pancreas, endoscopic pancreatic ultrasonography (EUS), and somatostatin receptor scintigraphy (SSRS), which are usually performed to locate an insulinoma, are not able to diagnose NIPHS. Moreover, SSRS can give a false-positive result. In this case report, we introduce a 22-year-old Thai woman who presented with fasting and postprandial hyperinsulinemic hypoglycemia. Accordingly, an insulinoma was suspected. She underwent several studies to locate the lesion. Pancreatic CT and EUS failed to locate a lesion; however, SSRS showed a faint focus of increased uptake at the pancreatic head. The suspected insulinoma was not identified during a first operation. Thereafter other diagnostic methods were performed in an effort to locate the suspected insulinoma, including selective arterial calcium stimulation test. The result of the selective arterial calcium stimulation test was negative. Intraoperative ultrasonography during a second operation also failed to locate a tumor. Finally, a pancreatic head resection was performed according to SSRS result, yet capillary blood glucose levels did not increase after resection. In response, a 95% pancreatectomy was performed. The pathology report was consistent with diffuse hyperinsulinism. This report emphasizes that SSRS can give false positive result in NIPHS.


Severe stroke: which medicine for which results?
In face of any severe stroke, the questions for health professionals in charge of the patient are: will the handicap be acceptable for the patient? But can we predict an acceptable handicap for the patient? For his family? When we know that the cognitive disorders, consequences of severe stroke often modify, in a major way, the behaviour of these patients? Given these difficulties for estimate vital and functional prognosis and even more the quality of life of patients with severe stroke, collective reflexions between physicians and nurses are essential, reflexions taking into account preferences and values of patients. Use of resuscitation resources for severe stroke patients implies to offer them the best rehabilitation. So, questions about health pathways for severe stroke are essential: which structures for these patients, which technologies, which medical, medico-social and social supports, which human accompaniment the society can propose to the patients and to their family, so that they have an acceptable quality of life.


Detection of methicillin resistance in Staphylococcus aureus by polymerase chain reaction and conventional methods: a comparative study.
Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide, which has emerged over the past 30 years as a leading cause of both nosocomial and community-acquired infections. Accurate and rapid identification of MRSA in clinical specimens is essential for timely decision on effective antimicrobial chemotherapy. The present study was conducted to compare two conventional phenotypic methods, oxacillin disk diffusion (ODD) method and mannitol salt agar (MSA) with oxacillin, with polymerase chain reaction (PCR) for mecA gene (as standard). A total of 165 consecutive clinical isolates of S. aureus received at the Department of Microbiology in our tertiary care teaching hospital were included in the study. All the isolates were subjected to ODD (1 μg) method, culture in MSA with oxacillin, and PCR for mecA gene. The sensitivity and specificity of ODD test were found to be 93.5% (86.4-97.3%) and 83.5% (79.2-85.8%), respectively, and that of MSA with oxacillin were found to be 87.1% (79.5-92.3%) and 89.3% (84.8-92.5%), respectively. The time taken for diagnosing MRSA by conventional methods is 48-72 h, which is more as compared to PCR which takes 18-24 h. This study recommends advocating PCR for mecA gene on a regular basis for detecting methicillin resistance in S. aureus isolates isolated from sterile body fluids or from special units such as intensive care units.


Characteristics of bioemulsifier V2-7 synthesized in culture media added of hydrocarbons: chemical composition, emulsifying activity and rheological properties.
The bioemulsifier V2-7 is an exopolysaccharide (EPS) synthesized by strain F2-7 of Halomonas eurihalina and it has the property of emulsifying a wide range of hydrocarbons i.e. n-tetradecane, n-hexadecane, n-octane, xylene mineral light and heavy oils, petrol and crude oil. Characteristics of exopolysaccharide V2-7 produced in media supplemented with various hydrocarbons (n-tetradecane, n-hexadecane, n-octane, xylene, mineral light oil, mineral heavy oil, petrol or crude oil) were studied. Yield production varied from 0.54 to 1.45 g L(-1) according to the hydrocarbon added, in the same way chemical composition, viscosity and emulsifying activity of EPS varied with the culture conditions. Respect to chemical composition, percentage of uronic acids found in exopolymers produced in hydrocarbon media was always higher than that described for V2-7 EPS (1.32%) obtained with glucose. This large amount of uronic acid present could be useful in biodetoxification and waste water treatment. On the other hand, the highest amount of biopolymer was synthesized with mineral light oil, while the most active emulsifiers were those obtained from media added with petrol and n-octane. Furthermore, all EPS were capable of emulsifying crude oil more efficiently than the three chemical surfactants tested as control (Tween 20, Tween 80 and Triton X-100). The capacity of strain F2-7 to grow and produce bioemulsifier in presence of oil hydrocarbons together with the high emulsifying activity and low viscosity power of the biopolymers synthesized in hydrocarbons media could be considered highly beneficial for application of both bioemulsifier and producing strain in bioremediation of oil pollutants.


Plasminogen/plasmin regulates alpha-enolase expression through the MEK/ERK pathway.
Previously we have demonstrated that both plasminogen (Plg) and plasmin (Pla) regulate the expression of the transcription factors c-FOS and EGR-1 [L.P. De Sousa, B.S. Brasil, B.M. Silva, M.H. Freitas, S.V. Nogueira, P.C. Ferreira, E.G. Kroon, C.A. Bonjardim, Plasminogen/plasmin regulates c-fos and egr-1 expression via the MEK/ERK pathway, Biochem. Biophys. Res. Commun. 329 (2005) 237-245]. Here we show that Plg activates the mitogen-activated protein kinases MEK and ERK which leads to alpha-enolase (alpha-ENO) gene expression not only in fibroblasts, but also in peripheral blood mononuclear cells. The alpha-ENO mRNA accumulation was apparent three hours post-Plg treatment and remained elevated out to 28h, a process that seems to require both de novo protein synthesis and active gene transcription. Pla mimics Plg-stimulated alpha-ENO expression through its serine protease activity, suggesting that conversion of Plg to active Pla is required. Pharmacological and genetic blockade of MEK caused inhibition of alpha-ENO mRNA accumulation, implicating MEK/ERK as the transduction pathway that leads to alpha-ENO expression upon Plg stimulation. Furthermore, Plg stimulated DNA binding activity of the transcription factors activator-protein 1 and early growth response gene-1 to their cognate regulatory sequences at alpha-ENO promoter. Altogether, our data show that Plg/Pla regulates alpha-ENO expression through the MEK/ERK pathway.


Rat mast cell phospholipase A2: activity toward exogenous phosphatidylserine and inhibiton by N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylserine.
The presence of phospholipase A2 in intact rat peritoneal mast cells was investigated by using two synthetic radiolabeled phosphatidylserine (PS) substrates. Incubation of intact cells with 1-oleoyl-2-[3H]oleoyl-PS resulted in the release of a considerable quantity of [3H]oleic acid from the substrate. To establish that [3H]oleic acid release was mediated via direct enzymatic attack at the sn-2 position, we measured release of the [3H]serine moiety from the glycerol backbone of 1,2-dimyristoylphosphatidyl[3H]serine. This activity, which represents the combined actions of phospholipases C and D, was 10-fold lower than [3H]oleic acid release, indicating that neither of these enzymes is required for the release of the preponderance of [3H]oleic acid. These results establish the existence in intact rat mast cells of a phospholipase A2 active toward exogenous PS. Over the concentration range at which exogenous PS activates mast cell secretion, intact mast cells and broken cells possessed nearly equal levels of phospholipase A2 activity, and enzyme activity was 3--4-fold higher toward PS than phosphatidylcholine. Several agents were tested for their ability to inhibit phospholipase A2 in intact mast cells. Of the agents tested, an N-substituted derivative of PS previously identified as an inhibitor of mast cell secretion was shown to be a particularly potent and efficacious inhibitor of mast cell phospholipase A2. The concentration dependence of enzyme inhibition paralleled inhibition of histamine secretion, providing a strong positive correlation between the level of phospholipase A2 in mast cells and the capacity for secretion.


[Calcium and the liver].
The concentration of cytosolic free calcium ([Ca2+]i) in living cells is far below than that of plasma and must be extruded against a large electrochemical gradient. Cytosolic Ca2+ is also concentrated by two organelles, the high-affinity, low-capacity endoplasmic reticulum and the low-affinity, high-capacity mitochondria. In liver, different hormones and neurotransmitters mobilize cell glucose by using Ca2+ as an amplifier signal. These agonists promote a fast and large increase in [Ca2+]i as detected by intracellular fluorescent indicators resulting from permeabilization of the endoplasmic reticulum and stimulation of the Ca2+ influx. The hormone action is mediated by rapid hydrolysis of inositol lipids with formation of two messagers inositol [1,4,5]triphosphate and diacylglycerol. Certain bile acids also promote a pronounced release of Ca2+ from the endoplasmic reticulum in liver but independently of the hormone messengers. Mobilization of cell Ca2+ and/or H+ by these cell messengers is involved in a wide variety of other cell functions.


Cement dust exposure and ventilatory function impairment: an exposure-response study.
We investigated cumulative total cement dust exposure and ventilatory function impairment at a Portland cement factory in Tanzania. All 126 production workers were exposed. The control group comprised all 88 maintenance workers and 32 randomly chosen office workers. Exposed workers had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEF), FEV1/FVC, FVC%, FEV1% and PEF%, than controls adjusted for age, duration of employment, height, and pack-years. Cumulative total dust exposure was significantly associated with reduced FVC, forced expiratory volume in 1 second, and peak expiratory flow rate adjusted for age, height and pack-years. Cumulative total dust exposure more than 300 mg/m year versus lower than 100 mg/m years was significantly associated with increased risk of developing airflow limitation (odds ratio = 9.9). The current occupational exposure limit for total cement dust (10 mg/m) appears to be too high to prevent respiratory health effects among cement workers.


Interaction of bacteriochlorophyll with the LH1 and PufX polypeptides of photosynthetic bacteria: use of chemically synthesized analogs and covalently attached fluorescent probes.
The protein components of the reaction center (RC) and core light-harvesting (LH 1) complexes of photosynthetic bacteria have evolved to specifically, but non-covalently, bind bacteriochlorophyll (Bchl). The contribution to binding of specific structural elements in the protein and Bchl may be determined for the LH 1 complex because its subunit can be studied by reconstitution under equilibrium conditions. Important to the determination and utilization of such information is the characterization of the interacting molecular species. To aid in this characterization, a fluorescent probe molecule has been covalently attached to each of the LH 1 polypeptides. The fluorescent probes were selected for optimal absorption and emission properties in order to facilitate their unique excitation and to enable the detection of energy transfer to Bchl. Oregon Green 488 carboxylic acid and 7-diethylaminocoumarin-3-carboxylic acid seemed to fulfill these requirements. Each of these probes were utilized to derivatize the LH1 beta-polypeptide of Rhodobacter sphaeroides. It was demonstrated that the beta-polypeptides did not interact with each other in the absence of Bchl. When Bchl was present, the probe-labeled beta-polypeptides interacted with Bchl to form subunit-type complexes much as those formed with the native polypeptides. Energy transfer from the probe to Bchl occurred with a high efficiency. The alpha-polypeptide from LH 1 of Rb. sphaeroides and that from Rhodospirillum rubrum were also derivatized in the same manner. Since these polypeptides do not oligomerize in the absence of a beta-polypeptide, reversible binding of a single Bchl to a single polypeptide could be measured. Dissociation constants for complex formation were estimated. The relevance of these data to earlier studies of equilibria involving subunit complexes is discussed. Also involved in the photoreceptor complex of Rb. sphaeroides and Rhodobacter capsulatus is another protein referred to as PufX. Two large segments of this protein were chemically synthesized, one reproducing the amino acid sequence of the core segment predicted for Rb. sphaeroides PufX and the other reproducing the amino acid sequence predicted for the core segment of Rb. capsulatus PufX. Each polypeptide was covalently labeled with a fluorescent probe and tested for energy transfer to Bchl. Each was found to bind Bchl with an affinity similar to the affinity of the LH 1 polypeptides for Bchl. It is suggested that PufX binds Bchl and interacts with a Bchlcalpha-polypeptide component of LH 1 to truncate, or interupt, the LH 1 ring adjacent to the location of the Q(B) binding site of the RC.


In situ electrochemical surface derivation of cobalt phosphate from a Co(CO3)0.5(OH)·0.11H2O nanoarray for efficient water oxidation in neutral aqueous solution.
In this Communication, cobalt phosphate (Co-Pi) has been successfully developed on a Co(CO3)0.5(OH)·0.11H2O nanoarray (CCH NA) on Ti mesh in neutral phosphate-buffered solution (PBS) via in situ electrochemical surface derivation. The resulting core@shell structured CCH@Co-Pi NA/Ti exhibits remarkable activity toward water oxidation with the need of an overpotential of 460 mV to achieve a geometrical catalytic current density of 10 mA cm-2 in 0.1 M PBS, with a high turnover frequency of and long-term electrochemical stability.


Moral enhancement, at the peak of pharmacology and at the limit of ethics.
The debate over the improvement of moral capacity or moral enhancement through pharmacology has gained momentum in the last decade as a result of advances in neuroscience. These advances have led to the discovery and allowed the alteration of patterns of human behavior, and have permitted direct interventions on the neuronal structure of behavior. In recent years, this analysis has deepened regarding the anthropological foundations of morality and the reasons that would justify the acceptance or rejection of such technology. We present a review of proposals for pharmacological interventions directed directly towards moral enhancement. In addition, we identify the ethical dilemmas that such interventions may generate, as well as the moral assessment of the authors of these studies. There is a moderate consensus on the risks of any intervention on the intimate structure of the human condition, its autonomy and identity, but there are large differences in explaining the reasons for this concern and especially in justifying such interventions. These findings show that it is necessary to investigate the moral assessment of authors and the ethical dimension within the field of pharmacology in order to identify future trends.


The role of the extracellular matrix in the development of heart valve disease: Underestimation or undercomprehension?
The function of metalloproteinases of the extracellular matrix and their inhibitors has emerged with a crucial role in valve diseases. Both the expression of matrix metalloproteinases and their inhibitors are susceptible to modification in patients with severe mitral insufficiency. This process is due to substantial changes in the collagen structure during mechanical stress on the mitral valve leaflets. Several studies have measured the level of deformation of the mitral leaflets with the use of the finite element analysis method by establishing the stiffness of the cellular and extracellular elements of the mitral valve leaflets. Evidence suggested the possible underestimation of the stiffness of the leaflets. This implies greater stress on the components of the extracellular matrix in the circumferential and radial strains that involve the mitral leaflets during chronic regurgitation. The remodeling process during mechanical stress phenomena involves both the cellular compartment and the extracellular matrix and can be adaptive or maladaptive as showed in patients who receive a pulmonary autograft to replace the diseased aortic valve. However, adaptive remodeling can be driven using resorbable polymers that interfere with the extracellular matrix. Further investigation is required for the understanding of the mechanisms that determine the structural changes of the extracellular matrix and to prevent them.


The adequacy of pharmacotherapy in outpatients with obsessive-compulsive disorder.
Pharmacotherapy and behavioural treatment are the main treatment options for patients with obsessive-compulsive disorder (OCD). Nevertheless, studies on the appropriateness of these treatments are scarce. We aimed to assess the adequacy of treatment in general, and pharmacotherapy in particular, in patients with OCD. Three hundred and thirteen outpatients with OCD were interviewed on admission at the University Medical Center (UMC) Utrecht, The Netherlands. Patients were evaluated for demographic and clinical characteristics. Current treatment was assessed on admission and treatment history was appraised retrospectively. On admission, only one-half of the patients took appropriate medication, of which 7.6% were prescribed maximal effective doses, 11.8% mean effective doses, 15% minimal effective doses and 19.4% ineffective doses. Approximately 35% of patients were prescribed no drugs and 16% inappropriate drugs. Although the majority of the patients had been treated on average three times prior to their current treatment, 24% had never received a serotonin reuptake inhibitor (SRI) or behaviour therapy. For approximately 50% of the total sample, the maximal effective dose of SRIs had never been taken during the course of treatment history. A large proportion of patients with OCD fail to receive adequate treatment. Many patients were prescribed SRIs at doses below those recommended for the guidelines.


Evaluation of CD44 variant 6 expression and clinicopathological factors in pulmonary metastases from colon carcinoma.
Although relatively little is known about the molecular mechanisms underlying tumor progression, recently CD44 glycoproteins and the c-Met receptor tyrosine kinase have been identified as potentially important components of the metastatic cascade. CD44 is a family of transmembrane receptors generated from a single gene by alternative splicing and differential glycosylation. Important biological processes involving CD44 glycoproteins include cell adhesion, lymphocyte homing, hematopoiesis, tumor progression and metastasis. The precise mechanism via which CD44 promotes tumorigenesis have not yet been elucidated. We evaluated the expression of adhesion molecule CD44 variant 6 in pulmonary metastases from colorectal carcinomas and its correlation with clinicopathological parameters. Twenty patients were randomly selected from the patients who had undergone a resection of pulmonary metastasis from colorectal cancer. Formalin-fixed, paraffin-embedded archival specimens of tumor tissues and adjacent normal mucosa from these patients were the subjects of the present study. Immunoreactivity for CD44 was quantified. Specimens were considered positive if almost 25% of the neoplastic cells were stained. CD44 v6 expression was related to the interval between colon resection and metastases diagnosis, the number of pulmonary metastases, and the survival after lung resection. No statistical correlation was found between CD44 v6 positivity and disease-free interval after colon resection, number of metastases or 2-year survival after lung resection. Probably CD44 v6 is necessary and sufficient to confer metastatic potential to carcinoma cells increasing the migration capacity and participating in invasion via changes in adhesion to the extracellular ligands, but is not necessary to modify the clinical history of the metastases. Therefore the evaluation of CD44 v6 expression in lung metastases does not influence the therapeutic scheme.


[Cortical hyperostoses after long-term prostaglandin E2 therapy].
Cortical hyperostoses are found to be side effects after therapy in early infancy with prostaglandin E1 and E2. Correlation seems to exist between dosage and duration of therapy. Radiologically the lesions cannot be differentiated from Caffey's disease. Pathogenetic relationship of the two diseases is discussed; 62 cases of newborn children with ductal related vitium cordis, who were treated for a short time or for longer with prostaglandin E2 are demonstrated.


Activation of nucleoplasmin, an oligomeric histone chaperone, challenges its stability.
Nucleoplasmin (NP) is a pentameric, ring-shaped histone chaperone involved in chromatin remodeling processes such as sperm decondensation at fertilization. Monomers are formed by a core domain, responsible for oligomerization, that confers the protein a high stability and compactness and a flexible tail domain, that harbors a polyglutamic tract and the nuclear localization signal. Fully activated NP presents multiple phosphorylated residues in the tail and in flexible regions of the core domain. In this work, we analyze the effect of activation on the structure and stability of the full-length protein and the isolated core domain through phosphorylation mimicking mutations. We have solved the crystal structure of an activated NP core domain that, however, is not significantly different from that of the wild-type,inactive, NP core. Nevertheless, we find that NP activation results in a strong destabilization of the pentamer probably due to electrostatic repulsion. Moreover, characterization of the hydrodynamic properties of both full-length and core domain proteins indicates that activating mutations lead to an expansion of the NP pentamer in solution. These findings suggest that NP needs a compact and stable structure to afford the accumulation of negative charges that weakens its quaternary interactions but is required for its biological function.


Positive and negative impacts of specialty malts on beer foam: a comparison of various cereal products for their foaming properties.
The foam stability of beer is dependent on the presence of foam-stabilizing polypeptides derived from the cereals from which it is made. It has long been argued that there is a tendency to boost the foam-stabilizing capabilities of these polypeptides at the heating stages involved in the production of the grist materials. The present study started with the intent to confirm whether these changes occurred and to assess the extent to which different cereal products differed in their foam-stabilizing tendencies. Cereal products differ enormously in their foam-stabilizing capabilities. Heavily roasted grains, notably black malt and roast barley, do have superior foaming properties. However, certain specialty malts, notably crystal malts, display inferior foam performance. The observed foaming pattern is a balance between their content of foam-positive and foam-negative components. Products such as pale malt do contain foam-negative materials but have a net balance in favour of foam-stabilizing entities. By contrast, wheat malt and especially black malt have a heavy preponderance of foam-positive components. Crystal malt displays the converse behaviour: it contains low-molecular-weight foam-negative species. Several of the cereal products appear to contain higher-molecular-weight foam inhibitors, but it appears that they are merely species that are of inherently inferior foam-stabilizing capability to the foaming polypeptides from egg white that were employed to probe the system. The foam-damaging species derived from crystal malt carried through to beers brewed from them. Intense heating in the production of cereal products does lead to enhanced foam performance in extracts of those products. However, not all speciality malts display superior foam performance, through their development of foam-negative species of lower molecular weight.


[Effect of acetylcholine and carbamylcholine on the resting membrane potential of denervated muscle in the rat].
The decrease of resting MP after denervation in diaphragm muscle of the rat was studied in vitro. Transitory activation of Na+,K+-pump by carbamylcholine, acetylcholine or adrenaline hyperpolarized the muscle fiber membrane but did not compensate the postdenervation fall of the MP. Similarly, the permanent presence of carbamylcholine at culturing media did not prevent the development of changes in the MP after denervation. The decrease of MP was accompanied by spontaneous release of acetylcholine for 24 hrs. Synaptic acetylcholine seems to play no obvious role in neurotrophic control of the resting MP.


Drug-induced Anaphylaxis.
Drug hypersensitivity is increasing worldwide as the consumption of drug is increasing. Many clinical presentations of drug hypersensitivity are complex and take place in the setting of illness and/or polypharmacotherapy. To review the most recent findings in the diagnosis and management of immediate drug hypersensitivity reactions. Studies were selected based on their relevance, originality and date of publication. The understanding of endotypes, biomarkers and phenotypes has improved the categorization of immediate hypersensitivity reactions. In this review, we discussed the short- and long-term management of anaphylaxis with a special focus on in vivo and in vitro diagnostic methods. Moreover, the clinical management of drug-induced anaphylaxis, the role of hidden allergens and the importance of delabeling are discussed. Endophenotyping is crucial to correctly diagnose and treat patients with immediate drug hypersensitivity reactions, preventing future episodes through drug desensitization.


A comparison of induced sister chromatid exchange levels in Chinese hamster ovary cells and cultured human lymphocytes.
Human lymphocytes and Chinese hamster ovary cells were exposed to DNA damaging agents for two cell cycles, and the induced sister chromatid exchange (SCE) rate was compared. CHO cells showed a significant increase in SCE following treatment with bleomycin and vincristine whereas human lymphocytes did not. Both CHO cells and lymphocytes showed an increase in SCE with 5-bromodeoxyuridine (BrdUrd) and tritiated uridine (3H-Urd) but the increase was greater in CHO cells. SCE levels were similar after exposure to proflavine and colcemid did not increase the exchange frequency in either cell type. Apparently CHO cells are more sensitive than human lymphocytes to the actions of bleomycin, vincristine, BrdUrd, and 3H-Urd. SCE analysis in response to mutagens and carcinogens should therefore be based on more than one cell type.


Facultative protein selenation regulates redox sensitivity, adipose tissue thermogenesis, and obesity.
Oxidation of cysteine thiols by physiological reactive oxygen species (ROS) initiates thermogenesis in brown and beige adipose tissues. Cellular selenocysteines, where sulfur is replaced with selenium, exhibit enhanced reactivity with ROS. Despite their critical roles in physiology, methods for broad and direct detection of proteogenic selenocysteines are limited. Here we developed a mass spectrometric method to interrogate incorporation of selenium into proteins. Unexpectedly, this approach revealed facultative incorporation of selenium as selenocysteine or selenomethionine into proteins that lack canonical encoding for selenocysteine. Selenium was selectively incorporated into regulatory sites on key metabolic proteins, including as selenocysteine-replacing cysteine at position 253 in uncoupling protein 1 (UCP1). This facultative utilization of selenium was initiated by increasing cellular levels of organic, but not inorganic, forms of selenium. Remarkably, dietary selenium supplementation elevated facultative incorporation into UCP1, elevated energy expenditure through thermogenic adipose tissue, and protected against obesity. Together, these findings reveal the existence of facultative protein selenation, which correlates with impacts on thermogenic adipocyte function and presumably other biological processes as well.


A systematic review: what factors predict Post-Traumatic Stress Symptoms in ambulance personnel?
Ambulance personnel are frequently exposed to traumatic accidents, which makes them a high risk for poor mental health. High rates of Post-Traumatic Stress Symptoms (PTSS) have been found within ambulance personnel samples but no review has been completed to examine the factors that may be implicated in the development of these symptoms. This literature review provides an overview of the factors that predict PTSS in ambulance personnel. A systematic search strategy was conducted in April 2020 across the following four databases: PsycINFO, PsycARTICLES, MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Eighteen papers were included in this review, and the predictive factors examined were grouped into four categories: coping style, personal factors, environmental factors and organisational factors. An array of factors across the four categories were implicated in the development of PTSS, but these tended to be indicated in only one or two papers. Evidence was found to suggest that dysfunctional coping styles, reduced levels of some personality traits, proximity and nature of the critical incident and high levels of organisation stress can all lead to PTSS. Further research is needed to support the reliability of findings.


Effectiveness of a Patient Support Program in Supporting Access to Therapy for Solid Tumor Malignancies.
Background: Certain governmental agencies, patient advocacy organizations, and pharmaceutical manufacturers have implemented programs to assist patients in overcoming barriers to accessing healthcare. Recently, such programs have expanded their services, helping both uninsured and insured patients to navigate the complex healthcare system, and assisting with increasing out-of pocket costs and copays for the drugs. Objective: To better understand the effect of patient support programs on access to therapy for solid tumor malignancies, this study evaluated service use, case outcomes, and patient characteristics from a manufacturer-sponsored program in the United States. Methods: Sociodemographic characteristics, services use rates, and outcomes by case and insurance type were evaluated at the patient- and case-level in a random sample of patients prescribed nab-paclitaxel for solid tumor malignancies who enrolled in the Celgene Patient Support (CPS) program (April 2011-November 2013). Results: This analysis included 4566 patients (8134 cases); most patients were female (64.7%), aged <65 years (59.2%), in the South (53.9%), and treated in community settings (87.9%). Patients were primarily insured by Medicare (38.5%) or commercial plans (37.3%), or were uninsured (16.6%). Following benefits investigations for new patients entering the program (98.5%), CPS provided support to obtain free medicine (29.4%), appeal denial of coverage (15.0%), receive commercial co-payment assistance (8.1%), or obtain prior payer authorization (1.3%). Nab-paclitaxel was provided at no cost in 89.4% of cases where patients sought financial support; payer reimbursement was obtained in 63.2% of reimbursement appeals. Of commercially-insured patients who required assistance with co-payments and met financial criteria, 93.3% received a mean of $597 in co-payment support. Conclusion: The CPS program was successful in gaining access to therapy. Healthcare providers and both insured or uninsured patients accessed CPS for prior authorization/precertification, appeals support, and financial support through the Free Medication Program and the Commercial Co-Pay program.


Histological changes of gingival epithelium in diabetic patients with periodontal disease.
The pathogenesis of the periodontal disease is complex, because it derives from the initiation and maintenance of the chronic inflammatory process by the plenty microbial flora and its numerous bacterial products. The purpose of our study was to make evidence of the histopathological changes occurring in the gingival epithelium in patients with both diabetes mellitus and periodontal disease. Our study was carried out on gingival tissue from 68 diabetic patients with specific symptoms of periodontitis. The preparations were processed by Hematoxylin-Eosin staining technique and trichromic staining after the Goldner-Szekely method. Although non-specific, since they have been generally found in chronic gingival inflammation, the noticed changes were significant and some of them had specific aspects for the diabetic patients: gingival epithelium changes like acanthosis type; the presence of inflammatory cells such as polymorphonuclear leukocytes and/or lymphocytes among the cells of the stratified squamous epithelium; surface ulceration areas covered by hematic and fibrino-leukocytary detritus; the epitheliocytes keratinization in the superficial layers. The diabetic patients with periodontitis frequently associate hypertrophy changes of the gingival epithelium with the epithelial permeability alteration and the presence of the intraepithelial inflammatory cells, subsequently leading to degenerative lesions and epithelial ulceration.


Allogeneic diabetic mesenchymal stem cells transplantation in streptozotocin-induced diabetic rat.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stroma cells which can provide a potential therapy for diabetes mellitus. But the mechanism is still controversial. Also, the status of BM-MSCs under hyperglycemia is not known. In the present study, we investigated the status of BM-MSCs in experimental-diabetic rat and demonstrated the rescue of experimental diabetes by diabetic MSCs transplantation. BM-MSCs were cultured and the potential of multiple-differentiation was identified through induction into osteoblasts. MSCs of passage 3 were used for the following experiment. The MSCs were labeled with 5-bromo-2?-deoxyuridine (BrdU). Diabetes in rats was induced by STZ injection. The rats were divided into three groups: normal control group (no DM, rats treated with saline through tail vein, n=10); DM control group (DM, no transplantation of MSCs, n=20); experimental group (DM and transplantation of MSCs, n=20). Body weight and blood glucose of the rats were monitored during the experiment after transplantation of MSCs. Paraffin sections of pancreas were obtained from rats of each group. Immuno-histochemistry analysis and double immunofluorescence were used to detect the BM-MSCs in the pancreatic tissue and their differentiating state. MSCs were 89.5% labeled by BrdU and DAPI, which was green/blue double stained under fluorescent microscopy. Transplantation of diabetic MSCs resulted in a reduction of hyperglycemia on day 45 in experimental diabetic rats compared with control rats (17.7 mM +/-3.9 vs 27.8 mM +/- 2.1, P < 0.05), There was also a difference between MSC-treated experimental diabetic rats and control rats in body weight (232.7 g +/-19.7 vs 133.3g +/-13.1, P < 0.05). Histological and morphometric analysis of the pancreas of experimental diabetic rats showed the presence and differentiation of transplanted MSCs into insulin-producing cells which evidenced by double-staining of anti-BrdU and insulin. Also, there were many small islets throughout the sections. Their mean area and diameter analysis revealed that they were smaller than control islets (1835.7 +/- 175.8 microm2 vs 13257.2 +/- 1457.6 microm2; 43.5 +/- 3.7 microm vs 119.9 +/- 5.8 microm, respectively, P < 0.05). Allogeneic MSCs transplantation can reduce blood glucose level in recipient rats. A relatively small quantity of transplanted diabetic MSCs survive and transdifferentiate into insulin-producing cells in the pancreas of recipient rats. Upon transplantation these cells initiate endogenous pancreatic regeneration by neogenesis of islet of recipient origin. The present study demonstrates that diabetic MSCs retains its stemness and potential to induce pancreatic regeneration on transplantation.


Domain structure and function of 10-formyltetrahydrofolate dehydrogenase.
10-Formyltetrahydrofolate dehydrogenase catalyzes the NADP(+)-dependent oxidation of 10-formyltetrahydrofolate to CO2 and tetrahydrofolate. Previous studies have shown that the enzyme binds the physiological pentaglutamate form of tetrahydrofolate product so tightly that it remains bound during size exclusion chromatography (Cook, R. J., and Wagner, C. (1982) Biochemistry 21, 4427-4434). In addition to the dehydrogenase activity, the enzyme from rat liver has been reported to exhibit both 10-formyltetrahydrofolate hydrolase and aldehyde dehydrogenase activities (Cook, R. J., Lloyd, R. S., and Wagner, C. (1991) J. Biol. Chem. 266, 4965-4973). We have purified the enzyme from rabbit liver and found that it catalyzes the same three reactions with similar kinetic constants and that it is a 99-kDa homotetramer, as reported previously for the rat and pig enzymes. Previous studies have suggested that the enzyme is composed of three domains and has separate folate binding sites for the dehydrogenase and hydrolase activities. We have investigated the domain structure of the rabbit enzyme. Differential scanning calorimetry reveals two thermal transitions, indicating the presence of two independently folded domains. The pentaglutamate form of tetrahydrofolate and NADP+ each stabilize one of the thermal transitions, showing that these ligands bind to separate domains. Limited proteolytic digestions by several proteases cleave the enzyme in a linker region between the two domains. After proteolytic cleavage, the domains no longer remain associated and do not catalyze the 10-formyltetrahydrofolate dehydrogenase reaction. Isolation and characterization of the intact domains revealed that the N-terminal domain only catalyzes the NADP(+)-independent 10-formyltetrahydrofolate hydrolase activity and the C-terminal domain only catalyzes the NADP(+)-dependent aldehyde dehydrogenase activity. The kinetic constants of these isolated domains are similar to those of the intact enzyme. Binding studies on the native enzyme using fluorescence and isothermal titration calorimetry indicated that the enzyme binds one molecule of tetrahydrofolate and two molecules of NADP+ per tetramer. Dissociation constants for both ligands were also determined by these methods.


Antipsychotic efficacy of the dopaminergic autoreceptor agonist EMD 49980 (Roxindol). Results of an open clinical study.
EMD 49980 is a dopamine agonist with selective affinity to dopamine autoreceptors. Following pharmacological findings in animal studies, it was postulated that a hyperactivity of dopaminergic neurons, which is possibly present in acute schizophrenia, may be reduced by autoreceptor stimulation. To investigate the antipsychotic efficacy of EMD 49980, 20 acutely ill schizophrenics (ICD No. 295.3) were treated over four weeks with dosage increasing up to 3 mg or 9 mg. According to previously defined criteria four patients were clear responders, but clinically none of them revealed a full remission. Ten patients were nonresponders, and three of these patients were drop-outs because of marked deterioration of schizophrenic symptoms. The explorative analysis of BPRS subscales shows a statistically significant reduction of anxiety/depression and anergia, but no clear influence on the subscales THOT, HOST, and ACTV, which are the more specific scales for acute schizophrenia. EMD 49980 was subjectively well tolerated and there was no case of drug-induced extrapyramidal side-effects. In view of the only moderate antipsychotic efficacy in acute schizophrenia and the fact that antidepressant and anxiolytic effects were also observed, a clinical investigation of EMD 49980 in affective disorders and in schizophrenia with depression or anergia should be performed.


Expression of FKBP prolyl isomerase 5 gene in tissues of muscovy duck at different growth stages and its association with muscovy duck weight.
FKBP prolyl isomerase 5 (FKBP5) has been shown to play an important role in metabolically active tissues such as skeletal muscle. However, the expression of FKBP5 in Muscovy duck tissues and its association with body weight are still unclear. In this study, real-time quantitative polymerase chain reaction was used to detect the expression of FKBP5 in different tissues of Muscovy duck at different growth stages. Further, single nucleotide polymorphisms (SNPs) were detected in the exon region of FKBP5 and were combined analyzed with the body weight of 334 Muscovy ducks. FKBP5 was highly expressed in various tissues of Muscovy duck at days 17, 19, 21, 24, and 27 of embryonic development. In addition, the expression of FKBP5 in the tissues of female adult Muscovy ducks was higher than that of male Muscovy ducks. Besides, an association analysis indicated that 3 SNPs were related to body weight trait. At the g.4819252 A>G, the body weight of AG genotype was significantly higher than that of the AA and the GG genotype. At the g.4821390 G>A, the genotype GA was extremely significantly related to body weight. At the g.4830622 T>G, the body weight of TT was significantly higher than GG and TG. These findings indicate the possible effects of expression levels in various tissues and the SNPs of FKBP5 on Muscovy duck body weight trait. FKBP5 could be used as molecular marker for muscle development trait using early marker-assisted selection of Muscovy ducks.


Vesicular and cytoplasmic localization of neurotensin-like immunoreactivity (NTLI) in neurons postsynaptic to terminals containing NTLI and/or tyrosine hydroxylase in the rat central nucleus of the amygdala.
Neurotensin and catecholamines in the central nucleus of the amygdala (CNA) have both been implicated in the integration of autonomic responses to stress. We examined whether there might be a cellular substrate for interactions involving these putative neurotransmitters in the CNA. Sections of acrolein-fixed rat brain were processed either (1) for the ultrastructural localization of a rat antiserum against neurotensin using the peroxidase-antiperoxidase (PAP) method, or (2) for the dual localization of rat neurotensin antiserum and rabbit antiserum against the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), using the PAP method and immunoautoradiography. The rat polyclonal antiserum against neurotensin was shown in immunoblots to recognize neuromedin N and Lys-Arg-neurotensin (LANT-6) in addition to neurotensin. In single and dual labeling studies, the neurotensin-like immunoreactivity (NTLI) was detected in perikarya and processes. The NTLI was localized predominantly to dense core vesicles in one group of perikarya and dendrites, while a second group had labeling both in dense core vesicles and more diffusely throughout the cytoplasm. Terminals also showed NTLI, particularly in association with dense core vesicles. The labeled terminals formed primarily symmetric junctions with both cell bodies and dendrites. In the dual labeling study, perikarya contained only NTLI while terminals contained TH and/or NTLI. Terminals containing TH or NTLI separately innervated cell bodies and dendrites displaying NTLI, and formed separate or convergent inputs onto unlabeled neuronal targets. Terminals colocalizing both TH and NTLI formed junctions only on unlabeled dendrites. These findings show that in the rat CNA two populations of neurons differ with respect to their distribution of NTLI, and that the output from neurons containing NTLI is modulated by direct synaptic input from terminals containing neurotensin and/or catecholamines. Release of neurotensin and catecholamines, most likely dopamine, from the same or separate terminals on common targets in the CNA may account for certain similarities in their stress-related functions.


Clinical decision-making in cardiac nursing: a review of the literature.
Clinical decision-making is an integral part of the professional nurse's role. This literature review aims to determine the present evidence available on clinical decision-making in cardiac nursing and to determine implications for practice and future research in this field.


[Effects of cranial radiotherapy on growth and hypothalamo-hypophyseal function].
Aiming at evaluating the possible adverse effects of the use of radiotherapy on the CNS in children, we studied fourteen patients in whom it was used: seven as part of the conventional prophylaxis we use in malignant lymphoproliferative processes (group I) and the remaining seven as a treatment for primary cerebral tumors (group II). We evaluated growth during periods ranging from 1.5 to 11 years, and also hypothalamic-pituitary function by RIA. We comment on the results and confirm the endocrine alterations, especially the deficit of growth hormone.


Theoretical Derivation of a Telephone-Based Health Coaching Intervention for Promoting Physical Activity and Healthy Nutrition.
Present research regarding interventions to change behavior suffers from insufficient communication of their theoretical derivation. This insufficient communication is caused by the restrictions imposed by most of the relevant scientific journals. This impedes further intervention development. In this article, a telephone-based health coaching (TBHC) intervention is introduced using a format outside these restrictions. This intervention is seen as a combination of (1) the activities performed with the target persons, i.e., its core, and (2) measures to ensure the quality of the intervention. The theoretical derivation of the core is presented. The core is seen to consist of (1) the style of coach-patient interaction and (2) the contents of this interaction. The style of coach-patient interaction was derived from self-determination theory and was concretized using motivational interviewing techniques. The contents of the coach-patient interaction were derived from the health action process approach and were concretized using behavior-change techniques. The derivation led to (1) a set of 16 coaching tools referring to the different states in which a patient might be and containing state-specific recommendations for performing the coaching session, and (2) guidelines for selecting the appropriate coaching tool for each session. To ensure the quality of the intervention, a coach-training program before and supervision sessions during the TBHC were added.


Lower omega-3 status associated with higher erythrocyte distribution width and neutrophil-lymphocyte ratio in UK Biobank cohort.
High red blood distribution width (RDW) is associated with decreased red blood cell deformability, and high neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and innate-adaptive immune system imbalance. Both RDW and NLR are predictors of chronic disease risk and mortality. Omega-3 index (O3I) values have previously been shown to be inversely associated with RDW and NLR levels. Our objective was to determine if total plasma long chain omega-3 fatty acids (Omega3%) measured in the UK Biobank cohort were associated with RDW and NLR values. RDW- and NLR- relationships with Omega3% were characterized in 109,191 adults (58.4% female). RDW- and NLR-Omega3% relationships were inversely associated with Omega3% (both p < 0.0001). These cross-sectional associations confirm previous findings that increasing RDW and NLR values are associated with low O3I. The hypothesis that RDW and/or NLR values can be reduced in individuals with less-than optimal long chain omega 3 values need to be tested in randomized controlled intervention trials using EPA and/or DHA.


Reduction of Confinement Error in Single-Molecule Tracking in Live Bacterial Cells Using SPICER.
Single-molecule tracking can extract quantitative kinetic information and identify possible state transitions of diffusing molecules (such as switching between binding and unbinding) in the in vivo environment of living cells. Confined diffusion, caused by the encompassing membrane boundary of the cell, results in increased uncertainties in identifying state-associated diffusion coefficients and transition probabilities. This problem is particularly acute in bacterial cells because of their small sizes. A standard approach to eliminating confinement errors in bacterial cells is to analyze molecule displacements only along the long axis of the cell, where molecules experience the least confinement, and hence turn three-dimensional tracking into a one-dimensional problem. However, this approach dramatically decreases the amount of data usable for statistical analysis and leads to increased uncertainties in identifying different states. Here, we present a simple algorithm, termed single-particle tracking improvement with confinement error reduction (SPICER), which significantly decreases confinement errors by selectively incorporating data not only from the long axis but also from the short axes of the cell. We validate SPICER using both reaction-diffusion simulations and experimental single-molecule tracking (SMT) data of RNA polymerase in live Escherichia coli cells. SPICER is easy to implement with existing SMT analysis routines and should find broad applications in SMT analysis.


Increased risk of acute myocardial infarction and stroke during hemorrhagic fever with renal syndrome: a self-controlled case series study.
We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke. Personal identification numbers from the Swedish HFRS patient database (1997-2012; n=6643) were cross-linked with the National Patient Register from 1987 to 2011. Using the self-controlled case series method, we calculated the incidence rate ratio of AMI/stroke in the 21 days after HFRS against 2 different control periods either excluding (analysis 1) or including (analysis 2) fatal AMI/stroke events. The incidence rate ratios for analyses 1 and 2 for all AMI events were 5.53 (95% confidence interval [CI], 2.6-11.8) and 6.02 (95% CI, 2.95-12.3) and for first AMI events were 3.53 (95% CI, 1.25-9.96) and 4.64 (95% CI, 1.83-11.77). The incidence rate ratios for analyses 1 and 2 for all stroke events were 12.93 (95% CI, 5.62-29.74) and 15.16 (95% CI, 7.21-31.87) and for first stroke events were 14.54 (95% CI, 5.87-36.04) and 17.09 (95% CI, 7.49-38.96). The majority of stroke events occurred in the first week after HFRS. Seasonal effects were not observed, and apart from 1 study, neither sex nor age interacted with the associations observed in this study. There is a significantly increased risk for AMI and stroke in the immediate time period after HFRS. Therefore, HFRS patients should be carefully monitored during the acute phase of disease to ensure early recognition of symptoms of impending AMI or stroke.


Disease hotspots or hot species? Infection dynamics in multi-host metacommunities controlled by species identity, not source location.
Pathogen persistence in host communities is influenced by processes operating at the individual host to landscape-level scale, but isolating the relative contributions of these processes is challenging. We developed theory to partition the influence of host species, habitat patches and landscape connectivity on pathogen persistence within metacommunities of hosts and pathogens. We used this framework to quantify the contributions of host species composition and habitat patch identity on the persistence of an amphibian pathogen across the landscape. By sampling over 11 000 hosts of six amphibian species, we found that a single host species could maintain the pathogen in 91% of observed metacommunities. Moreover, this dominant maintenance species contributed, on average, twice as much to landscape-level pathogen persistence compared to the most influential source patch in a metacommunity. Our analysis demonstrates substantial inequality in how species and patches contribute to pathogen persistence, with important implications for targeted disease management.


Influence of time interval between coronary angiography to off-pump coronary artery bypass surgery on incidence of cardiac surgery associated acute kidney injury.
Cardiac surgery associated acute kidney injury (CSA-AKI) is serious complication after cardiac surgery. The time interval between coronary angiography (CAG) to coronary artery bypass surgery (CABG) is proposed as modifiable risk factor for reduction of CSA-AKI. The aim of this study was to assess influence of time interval between CAG to off-pump CABG (OPCABG) on incidence of CSA-AKI. This was a retrospective observational study of 900 consecutive OPCABG patients who were classified into 2 groups based on time interval between CAG and OPCABG: ≤7 days or longer. The incidence of CSA-AKI was 24% (214/900) by Kidney Disease: Improving Global Outcomes (KDIGO) definition. The incidence of CSA-AKI was not significantly different in two groups (22% in >7 days groupvs. 28% in ≤7 days group, P = 0.31). The factors independently associated with CSA-AKI were: Age (OR 1.04; P = 0.002), baseline creatinine (OR 1.99,; P = 0.03), moderate LV dysfunction (OR 1.64,; P = 0.007) and blood transfusion (OR 3.3,; P < 0.001), but not the time interval between CAG and OPCABG. The incidence of CSA-AKI was highest in patients with creatinine clearance (CC) <50 mL/min when OPCABG was performed ≤7 days of CAG (16/38; 42%, OR 2.7, 1.4-5.4; P = 0.005) compared to lowest incidence of CSA-AKI in patients with CC >50 mL/min and OPCABG performed >7 days of CAG (114/543; 21%). This study demonstrated that there is no increased incidence of CSA-AKI if OPCABG is performed ≤7 days of CAG; but we recommend to postpone OPCABG for seven days if CC is <50 mL/min and there is no urgent indication for OPCABG in order to reduce incidence of CSA-AKI.


Corrective bracing for severe idiopathic scoliosis in adolescence: influence of brace on trunk morphology.
Aim. The aim of the work was to study whether wearing a corrective brace by adolescent girls with severe idiopathic scoliosis can influence external shape of the trunk. Methods. Comparison of clinical deformity of two groups of girls matched for age and Cobb angle: group (1) of 23 girls, aged 14.9 ± 1.3 years, Cobb angle 55.0° ± 6.8°, who refused surgical treatment and have been wearing Chêneau brace for more than 6 months, compared with group (2) of 22 girls, aged 14.1 ± 1.8 years, Cobb angle 59.7° ± 14.6° never treated with corrective bracing. Clinical deformity was assessed with the Bunnell scoliometer (angle of trunk rotation ATR) and surface topography (posterior trunk symmetry index POTSI and Hump Sum HS). Results. The ATR in the primary curvature was 11.9° ± 3.4° (5°-18°) in group 1 versus 15.1° ± 5.6° (6°-25°) in group 2 (P = 0.027). The HS was 16.8° ± 3.8 versus 19.2° ± 4.6, respectively, P = 0.07. The POTSI value did not differ between groups. Conclusion. Girls with Cobb angle above 45 degrees, who have been subjected to brace treatment, revealed smaller clinical deformity of their back comparing to nontreated girls having similar radiological curvatures.


Using weakly conserved motifs hidden in secretion signals to identify type-III effectors from bacterial pathogen genomes.
As one of the most important virulence factor types in gram-negative pathogenic bacteria, type-III effectors (TTEs) play a crucial role in pathogen-host interactions by directly influencing immune signaling pathways within host cells. Based on the hypothesis that type-III secretion signals may be comprised of some weakly conserved sequence motifs, here we used profile-based amino acid pair information to develop an accurate TTE predictor. For a TTE or non-TTE, we first used a hidden Markov model-based sequence searching method (i.e., HHblits) to detect its weakly homologous sequences and extracted the profile-based k-spaced amino acid pair composition (HH-CKSAAP) from the N-terminal sequences. In the next step, the feature vector HH-CKSAAP was used to train a linear support vector machine model, which we designate as BEAN (Bacterial Effector ANalyzer). We compared our method with four existing TTE predictors through an independent test set, and our method revealed improved performance. Furthermore, we listed the most predictive amino acid pairs according to their weights in the established classification model. Evolutionary analysis shows that predictive amino acid pairs tend to be more conserved. Some predictive amino acid pairs also show significantly different position distributions between TTEs and non-TTEs. These analyses confirmed that some weakly conserved sequence motifs may play important roles in type-III secretion signals. Finally, we also used BEAN to scan one plant pathogen genome and showed that BEAN can be used for genome-wide TTE identification. The webserver and stand-alone version of BEAN are available at http://protein.cau.edu.cn:8080/bean/.


Nonalcoholic Fatty Liver Disease Is Associated With Low Skeletal Muscle Mass in Overweight/Obese Youths.
Background: Recent studies in adult non-elderly and elderly individuals have reported a link between nonalcoholic fatty liver disease (NAFLD) and sarcopenia. Nonetheless, whether this relationship would be found outside these populations it is still unknown. Hence, we evaluated the relationship between NAFLD and skeletal muscle mass in children and adolescents with overweight/obesity. Methods: Two-hundred and thirty-four overweight/obese youths were enrolled. NAFLD was diagnosed by ultrasononography, after exclusion of infectious and metabolic disorders. Forty of the patients with NAFLD had also liver biopsy. Total and regional lean body mass and total fat mass measurements were obtained by dual-energy X-ray absorptiometry. The relative muscle mass (RMM) was defined as the percent of muscle mass (kg) relative to the sum of muscle and fat (kg) mass. Appendicular skeletal muscle mass (ASM) was calculated by the sum of muscle masses of the four limbs (kg), and expressed as percent of body weight. Results: Subjects were stratified according to tertiles of RMM. The prevalence of abdominal obesity, dyslipidemia, insulin resistance, metabolic syndrome, NAFLD as well as biopsy-proven nonalcoholic steatohepatitis (NASH) was significantly increased in the lowest tertile of RMM. After controlling for age, sex and Tanner stage, children in the lowest tertile of RMM had an increased risk for NAFLD (OR= 2.80, 95% CI=1.57-5.02) compared to those in the other two tertiles. This association persisted after additional adjustments for clinical and metabolic variables. Similarly, the risk of NAFLD in the lowest tertile of ASM/weight index was significantly higher compared to those in the other two tertiles after adjustment for the above confounders. Conclusions: This is the first study to establish an independent association between low muscle mass and NAFLD/NASH in overweight/obese youths. Considering the worldwide increase of pediatric obesity, measurements of muscle mass may serve as useful method of identifying among obese children those at high metabolic risk who may need intensive lifestyle interventions to prevent NAFLD and its progression.


Potential role of Lycium barbarum polysaccharides in glaucoma management: evidence from preclinical in vivo studies.
In recent years, the pharmacological benefits of herbal extracts have been revisited for their potential neuroprotective effects in glaucoma. The polysaccharides extracted from the fruits of Lycium barbarum L., or Lycium barbarum polysaccharides, exert their anti-aging effect through reducing oxidative stress, modulating the immune response, enhancing neuronal responses, and promoting cytoprotection. The therapeutic efficacy of Lycium barbarum polysaccharides in preserving retinal ganglion cells and their functions was demonstrated in a range of experimental models of optic neuropathies. These include the acute and chronic ocular hypertension models, the partial optic nerve transection model, and the ischemic-reperfusion injuries model. Based on these findings, Lycium barbarum polysaccharides appear to be a good candidate to be developed as a neuroprotective agent for treating multifactorial diseases. This review aims to present a comprehensive review on the latest preclinical evidence on the pre- and post-treatment benefits of Lycium barbarum polysaccharides in retinal ganglion cell neuroprotection. The possible mechanisms of Lycium barbarum polysaccharides mediating retinal ganglion cell neuroprotection will also be described. Moreover, the potential research gaps in the effective translation of Lycium barbarum polysaccharides treatment into clinical glaucoma management will be discussed.


Intra-cochlear electrode tip fold-over.
Cochlear implantation has been performed safely for over two decades but still has various minor and major complications. We report two cases of an unusual complication of electrode implantation: tip fold-over of the electrode array within the cochlea. Both cases required undergoing explantation and re-implantation. The frequent use of fine and pre-curved electrodes particularly with the use of an insertion tool necessitates routine postoperative radiological evaluation of the electrode array. Our cases demonstrate the benefit of systematic imaging including the possible use of the Cone Beam CT intraoperatively.


Second primary malignant neoplasms: a clinicopathological analysis from a cancer centre in India.
Patients diagnosed with a cancer have a life time risk of developing another de novo malignancy depending on various inherited, environmental and iatrogenic risk factors. Of late the detection of new primary has increased mainly due to refinement in both diagnostic and treatment modalities. Cancer victims are surviving longer and thus are more likely to develop a new metachronous malignancy. To report our observed trend of increase in prevalence of both synchronous and metachronous second malignant neoplasms among cancer victims and to review the relevant literature. A hospital based retrospective collection of prospective data of patients diagnosed with second denovo malignancy. The study was conducted over a 5 year period from July 2008 to June 2012. All patients diagnosed with a histologically proven second malignancy as per Warren Gate's criteria were included. Various details regarding sex, age at presentation, synchronous or metachronous, treatment and outcome were recorded. The occurrence of multiple primary malignancies is not rare. Awareness of the possibility alerts the clinician in evaluation of patients with a known malignancy presenting with unusual sites of metastasis. Individualizing the treatment according to the stages of the primaries will result in durable cancer control particularly in synchronous double malignancy.


Extensive cytoreductive surgery for appendiceal carcinomatosis: morbidity, mortality, and survival.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis. We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan-Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes. Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS. Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.


[Biomechanics of the skull and the bill in Ramphastos (Ramphastidae, Aves). II. Analysis of the conditions of movement of the bill].
As all the anatomical conditions are not present to permit any movement between the cranial segments, the bill aperture and closure by the rotation on the quadrato mandibular joint is, in Ramphastos , the only action studied in relation to muscles organization and bone architecture by torques analysis. From a mechanical advantage viewpoint, the beginning of the closure seems to be performed by velocity muscles, while the action is ended by power muscles. The stresses issued by the muscles actions are balanced by bone trabeculae and other muscles, and may be considered as responsible of the mechanical stiffness of the whole bill system.


Development and Validation of a Comprehensive Work-Related Needs Measure.
In a work context, employees tend to gravitate toward situations that are most conducive to meeting their needs. The purpose of this research is threefold. First, we define and specify the psychological needs under investigation, briefly highlight extant research, and differentiate needs from other individual difference variables. Second, we demonstrate the limitations of one of the most highly cited psychological needs instruments and introduce a new needs model. Third, we develop and evaluate a multi-dimensional needs inventory using a multi-study design. The strengths and limitations of the proposed and tested model are discussed, as are implications for future research.


Adult Tiger Man: A Case of Dermatomyositis Associated With Thymoma.
The scan demonstrated multiple linear and patchy hypermetabolic lesions in skeletal muscles, mimicking the coat of a tiger, and was referred to as "a tiger man" sign. A 38-year-old man was admitted to our hospital with weakness, shortness of breath, and muscle pain. A CT scan showed a mass in the anterior mediastinum. 18F-FDG PET/CT was performed to evaluate the mass with a preliminary diagnosis of thymoma; heterogeneous 18F-FDG uptake in the mediastinal mass and tiger man findings in skeletal muscles were observed in PET/CT images.


Use of Regional Anesthesia Techniques: Analysis of Institutional Enhanced Recovery After Surgery Protocols for Colorectal Surgery.
Principles of Enhanced Recovery After Surgery (ERAS®) protocols are well established, with the primary goal of optimizing perioperative care and recovery. The use of multimodal analgesia is a key component of these protocols, including regional analgesia techniques such as thoracic epidural analgesia (TEA), transversus abdominis plane (TAP), rectus sheath blocks or continuous wound infiltration (CWI)/catheters, and spinal anesthesia. We compare and contrast regional anesthesia approaches in different institutional colorectal surgery ERAS protocols. ERAS protocols for open and laparoscopic colorectal surgery were obtained from 15 different healthcare facilities mostly located in North American and one in New Zealand. A comparison was then made with respect to regional anesthesia recommendations. The most commonly used regional technique among protocols was TEA. TAP blocks were the next most common, with rectus sheath blocks and continuous wound catheters only mentioned in one protocol each. There are both similarities and differences in regional anesthesia techniques, which may be due to institution- and provider-level factors. Most protocols advocate for TEA use, which has been associated with a lower incidence of paralytic ileus, attenuation of the surgical stress response, improved intestinal blood flow, improved analgesia, and reduction of opioid use. Use of spinal anesthesia may lead to earlier mobilization compared to TEA, and lower doses of intrathecal morphine are recommended to reduce respiratory depression. TAP blocks were indicated for laparoscopic procedures. Rectus sheath blocks, which are listed in some protocols, may provide analgesia equivalent to epidural anesthesia, while avoiding complications of TEA. CWI has been effective in reducing postoperative pain, hastening recovery, and improving pulmonary function.


Studies on the ontogeny of goat hepatic cytochrome P-450-associated O-dealkylase activities using monoclonal antibodies: comparison to adult lung activity.
The P-450-associated O-dealkylase activity towards ethoxyresorufin (EROD) and pentoxyresorufin (PROD) was measured in liver microsomes from 1-day-, 1-week-, 4-week-, 6-week-old and adult goats in order to characterize the ontogeny of cytochrome P-450 in this species. The inhibition of these enzyme activities by monoclonal antibodies raised against 3-methyl-cholanthrene-induced (MAb 1-7-1) and phenobarbital-induced (MAb 2-66-3) rat hepatic cytochrome P-450 was used to measure the contribution of the MAb-defined, epitope-specific P-450 to the total activities during these ages of goat development. EROD activity was undetectable until the 1st week of life and increased more than 25-fold by 4 weeks of age. The inhibition of EROD by MAb 1-7-1 increased from 20% in 1-week-old to 70% in adult goats. PROD activity, however, was detectable in the 1-day-old and reached adult levels by 6 weeks of age. The maximal inhibition (40%) of PROD activity by MAb 2-66-3 was demonstrated in 1-day-old goats. The measurement of these enzyme activities and their inhibition by the monoclonal antibodies demonstrated major differences in the ontogeny of these P-450 isozymes in goats. On the other hand, adult goat lung lacked detectable PROD activity, while it expressed approximately one tenth of the EROD activity exhibited by the liver. Over 70% of this activity was inhibitable by MAb 1-7-1.