Functional profile of the binary brain corticosteroid receptor system: mediating, multitasking, coordinating, integrating.
This contribution is focused on the action of the naturally occurring corticosteroids, cortisol and corticosterone, which are secreted from the adrenals in hourly pulses and after stress with the goal to maintain resilience and health. To achieve this goal the action of the corticosteroids displays an impressive diversity, because it is cell-specific and context-dependent in coordinating the individual's response to changing environments. These diverse actions of corticosterone are mediated by mineralocorticoid- and glucocorticoid-receptors that operate as a binary system in concert with neurotransmitter and neuropeptide signals to activate and inhibit stress reactions, respectively. Classically MR and GR are gene transcription factors, but recently these receptors appear to mediate also rapid non-genomic actions on excitatory neurotransmission suggesting that they integrate functions over time. Hence the balance of receptor-mediated actions is crucial for homeostasis. This balanced function of mineralo- and glucocorticoid-receptors can be altered epigenetically by a history of traumatic (early) life events and the experience of repeated stressors as well as by predisposing genetic variants in signaling pathways of these receptors. One of these variants, mineralocorticoid receptor haplotype 2, is associated with dispositional optimism in appraisal of environmental challenges. Imbalance in receptor-mediated corticosterone actions was found to leave a genomic signature highlighting the role of master switches such as cAMP response element-binding protein and mammalian target of rapamycin to compromise health, and to promote vulnerability to disease. Diabetic encephalopathy is a pathology of imbalanced corticosterone action, which can be corrected in its pre-stage by a brief treatment with the antiglucocorticoid mifepristone.


Fertility tables of two populations of the parthenogenetic species Poratia salvator (Diplopoda, Polydesmida, Pyrgodesmidae).
Diplopods are very susceptible to various degrees of environmental disturbance, particularly climate, altitude and diet. In order to increase our understanding of millipede ecological plasticity, we used fertility tables to access and to compare the fertility and survival of two populations of the parthenogenetic species Poratia salvator from two areas with distinct characteristics. Collecting was conducted in two localities within the state of Mato Grosso, in the Pantanal of Mato Grosso, municipality of Nossa Senhora do Livramento, and in the municipality of Várzea Grande. The specimens were maintained at room temperature. In the first generation, individuals from the Pantanal of Mato Grosso population reproduced early and also died earlier when compared with individuals from the Várzea Grande population. Furthermore, the population from the Pantanal had a lower net reproduction rate and a higher intrinsic growth rate than the population from the Várzea Grande. The generation time was lower for the Pantanal population than for the Várzea Grande population. In the second generation, the net reproduction rate observed for both populations was higher than that observed in the first generation, suggesting an increase in the reproductive potential of the females throughout their lives. The intrinsic growth rate of both populations decreased as a function of an increase in generation time observed in the second generation. As a result, the population growth rate in the second generation was slower when compared with the first generation, probably a result of the longer life expectancy of the second generation, which may have become adapted to the artificial conditions of the experiment.


Multilevel, room-temperature nanoimprint lithography for conjugated polymer-based photonics.
We demonstrate the multilevel patterning of organic light-emitting polymers by room-temperature nanoimprint lithography (RT-NIL), which is impossible to obtain by conventional hot embossing. In particular, we realize one- and two-dimensional photonic crystals with 500 nm periodic features and investigate the changes in the optical properties (luminescence and quantum yield) of the organic active layer. An increase of the quantum yield by 2.4% for the patterned film with respect to the untextured one and the enhancement of the output light emitted at a particular angle (Theta = 69 degrees) are observed for gratings whose Bragg periodicity matched the emission wavelength of the polymer. The employment of RT-NIL to pattern polymer semiconductors without degradation of their optical properties represents a strategic route for the realization of novel nanopatterned optoelectronic devices.


Application of lactic acid derived from food waste on pathogen inactivation in fecal sludge: a review on the alternative use of food waste.
Food waste generation and disposal have led to several environmental problems, especially in developing countries. This phenomenon is partly because most cities rapidly urbanize, which results in population increase, urban settlement and waste generation. Improper management of waste has continued to create environmental problems. These problems have indeed interfered with the inadequate measures in managing other organic waste such as food waste. Food waste can be fermented and used for pathogen inactivation in fecal sludge (FS). The continual decrease in global crop production due to soil erosion, nutrient runoff and loss of organic matter has generated interest in using FS for soil amendment. However, due to the high number of pathogens in FS that are harmful to humans, FS must be treated before being used in agriculture. Thus, given the high amounts of food waste generated globally and the lactic acid potential of fermented food waste, several researchers have recently proposed the use of fermented food waste to suppress pathogens in FS. This review presents the various approaches in pathogen inactivation in FS using different types of food waste. On the basis of the literature review, the major problems associated with the generation, collection and application of food waste in pathogen inactivation in FS are discussed. Moreover, the trends and challenges that concern the applicability of each method are critically reviewed.


[Socio-epidemiological and cultural aspects of cutaneous leishmaniasis: conceptions, attitudes and practices in the populations of Tierralta and Valencia (Cordoba, Colombia)].
This article focuses on the conceptions, attitudes and practices of the inhabitants from four villages (veredas) in Tierralta and Valencia (Cordoba, Colombia), who have suffered from or are aware of the existence of cutaneous leishmaniasis. A mixed methodology was implemented based in a qualitative design using interviews and focus groups (n=45) and an epidemiological design which included applying the Montenegro test (n=251), uncovering suspected cases of cutaneous leishmaniasis in humans, (n=5) and applying epidemiological surveys (n=409). Among the results, a lack of knowledge regarding the vector was found; although respondents could identify the Lutzomyia (known as "alú"), they did not correlate it with cutaneous leishmaniasis. In addition, traditional home treatments were more frequently used, increasing the underrecording of cases. With respect to healthcare personnel, flaws in diagnosis and treatment were found, which reinforces adherence to home treatments. This scenario calls for a reflection upon the challenges of the health care system in relation to the interventions of health personnel in communities situated in endemic areas.


Early short-term ivabradine treatment in new-onset acute systolic heart failure and sinus tachycardia patients with inflammatory rheumatic disease.
Acute heart failure (AHF) is a common complication of inflammatory rheumatic disease (IRD) and usually coexists with tachycardia. Ivabradine, a direct sinus node inhibitor, which was proven to have favorable effects in patients with chronic HF (CHF), has not been sufficiently evaluated in AHF patients regarding its efficacy and safety. The present study sought to explore the effectiveness of early short-term ivabradine treatment in new-onset AHF and concurrent sinus tachycardia in patients with IRD. A total of 12 consecutive patients with IRD, who had new-onset AHF and concurrent sinus tachycardia, were prescribed ivabradine and were retrospectively recruited. Standard medication therapy for AHF was also administered. The heart rate (HR), left ventricular ejection fraction (LVEF), biomarkers of HF and New York Heart Association (NYHA) classification score were compared prior to and after ivabradine treatment. After 48 h of treatment with ivabradine, the mean resting HR decreased from 118.0±13.8 to 83.3±7.3 bpm (P<0.001). Transthoracic echocardiography indicated a significant improvement in the LVEF on an average of 2 weeks after ivabradine prescription when compared with the baseline evaluation (51.2±8.4 vs. 38.0±9.0%; P<0.001). In addition, ivabradine treatment resulted in significantly decreased N-terminal proB-type natriuretic peptide (4,900±3,672 vs. 16,806±16,130 pg/ml; P=0.045) and improvement of the NYHA classification score (2.3±0.6 vs. 3.5±0.5; P<0.001) at 2 weeks when compared with the baseline. Overall, the results of the present study suggested that early use of ivabradine is safe in IRD patients with new-onset AHF and enhances the sinus rate reduction, which may improve heart function.


Ubiquitin receptors are required for substrate-mediated activation of the proteasome's unfolding ability.
The ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates were degraded with greater processivity (with a higher tendency to be unfolded and degraded than released) than ubiquitin-independent substrates. Thus, even though ubiquitin chains are removed before unfolding and degradation occur, they affect the unfolding of a protein domain. How do ubiquitin chains activate the proteasome's unfolding ability? We investigated the roles of the three intrinsic proteasomal ubiquitin receptors - Rpn1, Rpn10 and Rpn13 - in this activation. We find that these receptors are required for substrate-mediated activation of the proteasome's unfolding ability. Rpn13 plays the largest role, but there is also partial redundancy between receptors. The architecture of substrate ubiquitination determines which receptors are needed for maximal unfolding ability, and, in some cases, simultaneous engagement of ubiquitin by multiple receptors may be required. Our results suggest physical models for how ubiquitin receptors communicate with the proteasomal motor proteins.


Effects of a tobacco ban on long-term psychiatric patients.
A total ban on all tobacco products was implemented in a diverse psychiatric institution. A post hoc evaluation examined the effect of the ban on long-term patients by comparing their characteristics the year before the ban to the year after. Several variables measuring physical health, psychiatric symptomatology, feelings of well-being, and interpersonal conflict were coded with very high reliability from health records. For the majority of patients who were in the maximum security forensic division, the tobacco ban was associated with almost no detectable ill effects with some clear benefits. Among the remainder of the long-term patients, the ban might have been associated with a temporary increase in physical aggression towards staff members. It was concluded that successful implementation, and the avoidance of ill effects, depended entirely on the success staff members had in actually preventing patient access to tobacco.


Percutaneous leverage technique for reduction of radial neck fractures in children: technical tips.
Paediatric radial neck fractures are challenging to treat. Multiple strategies exist for reduction and fixation; there is no clear consensus on the best surgical technique to achieve reduction. The percutaneous leverage technique is a method for reduction of radial neck fractures that has previously been described by Wallace, though there is a lack of published literature on this technique. We present a technical note and a modest case series on our modification to the percutaneous leverage technique accompanied by intramedullary fixation. We describe a retrospective series of patients who underwent the modified percutaneous leverage technique for paediatric radial neck fracture reduction followed by flexible intramedullary nail fixation at a single Level I trauma centre from 2008 to 2016. This technique involves making a small incision over the dorsal border of the ulna and using a blunt curved surgical forceps to dissect towards the ulnar border of the radius just distal to the radial neck fracture site. The curved forceps is then used to push the radial shaft away from the ulnar shaft which reduces the radial neck fracture. Intramedullary fixation is then utilized to stabilize the reduction. Pre- and postoperative radiographs and clinical data from the medical record were reviewed, and patient, injury and treatment characteristics as well as complication rates are summarized. We successfully treated a series of eight radial neck fractures with the modified percutaneous leverage technique. This technique allows for a small incision and a minimally invasive method for the reduction of paediatric radial neck fractures. This allowed for subsequent intramedullary fixation and early postoperative elbow mobilization. In our series, no patients developed synostoses or sustained peripheral nerve injuries using this technique. The modified percutaneous leverage technique followed by intramedullary fixation is a safe and effective technique for fixation of displaced paediatric radial neck fractures. Level IV.


Lack of Association between the MiR146a Polymorphism and Susceptibility to Thai Childhood Acute Lymphoblastic Leukemia.
MiRNAs, small non coding RNAs, play a role in the regulation of hematopoiesis, with effects on cell growth, differentiation, and apoptosis. In addition, MiRNAs are thought to play an important role in tumorigenesis. The miR146a G>C polymorphism can lead to alteration of miR146 expression, which appears to be associated with development and progression of several cancers. This study aimed to investigate the association of the miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. Totals of 100 childhood ALL patients and 200 healthy children were studied for miR146a polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). The frequency of the miR146a G allele in controls was 0.40 compared with 0.38 in ALL patients. There was no association between miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood ALL (OR=1.484, 95%CI=0.712-3.093, p=0.290). Moreover, the frequencies of miR146a (rs2910164) G>C polymorphism were not associated with demographic data and clinical outcomes in ALL cases. The miRNA146a polymorphism was not significantly associated with susceptibility to Thai childhood ALL or any clinico-pathological variables.


[Adrenal tumours in a selected 10-years surgical material].
The aim of the study was to analyze the number and proportions of different adrenal tumours resected during the last 10 years in our centre. Besides, we seek correlations between the size of tumours and the age and body mass indexes (BMI) of the examined patients. The tumours where measured on CT and MRI before surgery, and on pathological examination after resection. The examined group consisted of 69 patients, 22 males and 47 females, mean age 50.51 +/- 12.26 yrs. In 45 (65.22%) cases the right adrenal was affected, in 21 (30.43%)--the left, in 3 (4.35%)--both. 12 adrenocortical cancers, 20 phaeochromocytomas, 9 cortisol-secreting adenomas, 4 aldosteronomas, 18 hormonally inactive adenomas, 6 miscellaneous tumours were found. Malignant tumours where significantly larger than benign (12.20 +/- 6.81 vs 6.71 +/- 5.62 cm, p < 0.005). We observed no correlation between the age and preoperative tumor size (p = 0.1756), between the age and pathological tumor size (p = 0.3601), and between BMI and the preoperative and histopathologic size (p = 0.4204, and p = 0.6478, respectively). The most common tumour was phaeochromocytoma. Most tumours where found in the right adrenal. The malignant tumours where larger than benign ones. No correlations between age and BMI, and tumour size where demonstrated.


The spectrum of spitzoid tumours: A clinical study.
This study explores the relationship between different types of spitzoid tumours, spindle cell naevus of Reed and spitzoid melanomas. Clinical and histopathological data were retrospectively reviewed from our hospital database in Cambridge from January 2006 to July 2009. Clinical images, where available, were recorded. Search headings from our pathology database included 'spitzoid tumours', 'Spitz naevi', 'atypical spitzoid tumours', spitzoid tumours of uncertain malignant potential ('STUMP'), 'spindle cell naevus of Reed' and 'spitzoid melanomas'. The total number of spitzoid tumours was 118 comprising Spitz naevi (72), atypical spitzoid tumours (30), spitzoid melanomas (eight), and other naevi with spitzoid features (eight). In total, 60% of Spitz naevi were diagnosed clinically and 50% reported a history of change with spitzoid melanoma, compared with 32% with Spitz naevi. In all, 60% of Spitz naevi and atypical spitzoid tumours were pigmented in contrast with spitzoid melanomas (83%). Variegated pigmentation was found in 20% of Spitz naevi and atypical spitzoid tumours, however, no spitzoid melanomas had mixed pigmentation. There were 30 atypical spitzoid tumours (9 M : 21 F); 16 occurred on the lower limbs, peaking in the 20-30-years age group. There were eight patients with spitzoid melanomas with a 7:1 F : M ratio, 50% of which were diagnosed clinically. Of the 34 spindle cell naevus of Reed (10 M : 24 F), 31 were misdiagnosed, most commonly as melanoma. Reed naevi peaked in the 30-40 year age group and on the upper limbs and lower limbs in the 20-30-years age group. In summary, age and sex appeared helpful in distinguishing benign from malignant spitzoid tumours, however history was less discriminatory. Spitzoid melanomas, most of which were pigmented occurred more commonly in females. Atypical spitzoid tumours were more common in females and pathologists favoured malignancy in this group beyond 20 years of age.


The Bidirectional Relation Between Counterfactual Thinking and Closeness, Controllability, and Exceptionality.
In four experiments, we explored the inferences people make when they learn that counterfactual thinking has occurred. Experiment 1 (N = 40) showed that knowing that a protagonist had engaged in counterfactual thinking (compared to no counterfactual thinking) resulted in participants inferring that the past event was closer in time to the protagonist, but there was no difference in inferring how close the past event was between knowing that a protagonist made many or a single counterfactual statement(s). Experiment 2 (N = 80) confirmed that participants were not affected by the number of counterfactual statements they read when inferring temporal closeness. Experiment 3 (N = 49) demonstrated that participants who learned that a protagonist had engaged in counterfactual thinking were more likely to infer that the protagonist experienced the controllable event. Experiment 4 (N = 120) indicated that participants who learned that a protagonist had engaged in counterfactual thinking were more likely to infer that the protagonist experienced the exceptional event. We concluded that the existence (but not the number) of counterfactual thoughts can lead people to infer that events were close, exceptional, and controllable, which suggests that the relations between closeness/controllability/exceptionality and counterfactual thinking are bidirectional. These results showed that as well as making inferences based on facts about the real world, people also make inferences about the real world based on hypothetical worlds.


Impact of pre-existing immunity on the induction of functional cross-reactive anti-hemagglutinin stalk antibodies following vaccination with an AS03 adjuvanted pandemic H1N1 vaccine.
The 2009 pandemic H1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin (HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naïve to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemic before pandemic vaccines became available. Here, we evaluated how pre-existing antibodies influence the induction of cross-functional HA stalk antibodies following A(H1N1)pdm09 vaccination. Fifty-six healthcare workers vaccinated with AS03 adjuvanted A(H1N1)pdm09 vaccine were chosen by their pre-vaccination priming status (primed HI titers ≥ 40 or unprimed < 40). We analyzed the HA head- and stalk-specific serum IgG subclasses at pre- and 21 days post-vaccination. We also assessed the functionality of the HA stalk-specific antibodies to neutralize virus and mediate antibody dependent cellular cytotoxicity (ADCC). Primed individuals had higher pre-existing HA head- and stalk-specific IgG1, as well as higher ADCC functionality of stalk antibodies. However, following vaccination with the adjuvanted pandemic vaccine, only the quantity of HA head specific IgG1 antibodies were significantly higher than in unprimed individuals. The priming status did not impact upon the cross-reactive HA stalk specific IgG antibodies or their ability to neutralize virus or induce ADCC post-vaccination. In conclusion, a single dose of AS03 adjuvanted pandemic vaccine elicited similar levels of functional antibodies in naïve and primed individuals. These findings are important for understanding the immunological factors that impact or modulate pandemic vaccine responses in humans.


Estimation of x ray overexposure in a childhood leukaemia cluster by means of chromosome aberration analysis.
Only multiple X ray diagnostics could be identified as a common risk factor in a leukaemia cluster that appeared between 1985-1989 in the municipality of Sittensen in northern Germany. In order to judge if the effect could be explained by irradiation dose, estimates were done in two of the leukaemia cases and seven former patients of a practice where some of the leukaemia cases had been treated for orthopaedic reasons. The methods used for the reconstruction of doses were physical simulation and biological dosimetry by dicentric chromosomes in peripheral lymphocytes. Compared to the Bremen laboratory control the mean frequency of dicentric chromosomes in the lymphocytes of the seven volunteers was significantly elevated. An overexposure of about 12-fold could be derived compared to state of the art X raying. At least two cases of the leukaemia cluster in Sittensen can therefore be correlated to an overexposure by diagnostic X rays.


[Prevalence of Risk Factors of Non-Communicable Disease in Kyrgyzstan: Assessment using WHO STEPS Approach].
Assessment of prevalence of risk factors for non-communicable diseases (NCD) based on WHO "STEPS" approach was conducted in Kyrgyzstan. Results of this study demonstrated high prevalence of NCD risk factors: 94.2% of subjects aged 24-64 years had risk factors. Prevalence of elevated blood pressure was 48.7, smoking - 25.7, hypercholesterolemia - 23.6, excessive alcohol consumption - 31.4, physical inactivity 11.4, obesity - 23.1, elevated glucose level - 4.5, diabetes - 8.8, inadequate intake of fruits and vegetables - 74%. The data obtained would allow to draft effective preventive measures to combat NCD risk factors at the national level.


Effect of cholesterol on apolipoprotein A-I binding to lipid bilayers and emulsions.
The effects of cholesterol (Chol) on the interaction of apolipoprotein A-I (apoA-I) with phospholipid bilayer vesicles and lipid emulsions were investigated. ApoA-I bound to phosphatidylcholine (PC) vesicles with higher affinity and lower capacity compared to triglyceride-PC emulsions. An increase in surface Chol in triglyceride-PC emulsions decreased the binding capacity without changing the binding affinity. In contrast, addition of Chol to PC vesicles caused a marked increase in capacity and decrease in affinity for apoA-I binding. ApoA-I caused a large release of entrapped aqueous dye, calcein, from PC vesicles, whereas this apoA-I-induced leakage was relatively small in the vesicles containing Chol. The incorporation of phosphatidylethanolamine into the vesicles also exerted effects similar to those of Chol on apoA-I binding and calcein leakage. The shifts of fluorescence emission maximum of dansyl lysine, probing the surface region of membranes, indicated that Chol as well as phosphatidylethanolamine increased the headgroup space of the vesicles. The binding maximum of apoA-I was closely correlated with the emission maximum of dansyl lysine, not with the fluorescence anisotropy of I-[4-(trimethylamino)phenyl]phenylhexatriene, suggesting that the binding capacity of apoA-I to the bilayer surface was modulated by the headgroup space rather than the acyl chain fluidity. These results show that Chol affects the bilayer surface so as to allow more apoA-I to bind to bilayers and may suggest the possibility of the interaction of apoA-I with Chol-enriched membrane domains.


Mechanical shedding of L-selectin from the neutrophil surface during rolling on sialyl Lewis x under flow.
The interaction of L-selectin expressed on leukocytes with endothelial cells leads to capture and rolling and is critical for the recruitment of leukocytes into sites of inflammation. It is known that leukocyte activation by chemoattractants, the change of osmotic pressure in cell media, or cross-linking of L-selectin all result in rapid shedding of L-selectin. Here we present a novel mechanism for surface cleavage of L-selectin on neutrophils during rolling on a sialyl Lewis x-coated surface that involves mechanical force. Flow cytometry and rolling of neutrophils labeled with Qdot(R)-L-selectin antibodies in an in vitro flow chamber showed that the mechanical shedding of L-selectin occurs during rolling and depends on the amount of shear applied. In addition, the mechanical L-selectin shedding causes an increase in cell rolling velocity with rolling duration, suggesting a gradual loss of L-selectin and is mediated by p38 mitogen-activated protein kinase activation. Thus, these data show that mechanical force induces the cleavage of L-selectin from the neutrophil surface during rolling and therefore decreases the adhesion of cells to a ligand-presenting surface in flow.


Identification of a hybrid PKS-NRPS required for the biosynthesis of NG-391 in Metarhizium robertsii.
The fungal entomopathogen Metarhizium robertsii (formerly known as M. anisopliae var. anisopliae) is a prolific producer of secondary metabolites of which very little is known at the genetic level. To establish the genetic bases for the biosynthesis of the mutagenic compound NG- 391, we identified a 19,818 kb genomic region harboring the predicted hybrid polyketide synthase-nonribosomal peptide synthetase NGS1, plus five additional ORFs. NGS1 knockouts generated by Agrobacterium-mediated transformation failed to produce detectable levels of NG-391, indicating the involvement of this locus in its biosynthesis. NGS1 deletion mutants had no significant changes in virulence levels against larvae of Spodoptera exigua and in resistance to hydrogen peroxide-generated oxidative stress compared to the wild-type strain. All 6 ORFs were expressed in medium supporting production of NG-391, and NGS1 was expressed during the interaction with the S. exigua host. The use of an NGS1 promoter-GFP reporter fusion showed that during in vitro growth in still broth cultures, NGS1 expression is restricted to the early exponential phase and is affected by M. robertsii cell density.


Characteristics of postintensive care syndrome in survivors of pediatric critical illness: A systematic review.
To synthesize the available evidence focusing on morbidities in pediatric survivors of critical illness that fall within the defined construct of postintensive care syndrome (PICS) in adults, including physical, neurocognitive and psychological morbidities. A comprehensive search was conducted in MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and CINAHL using controlled vocabulary and key word terms to identify studies reporting characteristics of PICS in pediatric intensive care unit (PICU) patients. Two reviewers independently screened all titles and abstracts and performed data extraction. From the 3176 articles identified in the search, 252 abstracts were identified for full text review and nineteen were identified for inclusion in the review. All studies reporting characteristics of PICS in PICU patients were included in the final synthesis. Nineteen studies meeting inclusion criteria published between 1995 and 2016 were identified and categorized into studies reporting morbidities in each of three categories-physical, neurocognitive and psychological. The majority of included articles reported prospective cohort studies, and there was significant variability in the outcome measures utilized. A synthesis of the studies indicate that morbidities encompassing PICS are well-described in children who have survived critical illness, often resolving over time. Risk factors for development of these morbidities include younger age, lower socioeconomic status, increased number of invasive procedures or interventions, type of illness, and increased benzodiazepine and narcotic administration. PICS-related morbidities impact a significant proportion of children discharged from PICUs. In order to further define PICS in children, more research is needed using standardized tools to better understand the scope and natural history of morbidities after hospital discharge. Improving our understanding of physical, neurocognitive, and psychological morbidities after critical illness in the pediatric population is imperative for designing interventions to improve long-term outcomes in PICU patients.


Real-time fluorescence monitoring of phenothiazinium photosensitizers and their anti-mycobacterial photodynamic activity against Mycobacterium bovis BCG in in vitro and in vivo models of localized infection.
An objective was to explore the photodynamic activity of two cationic photosensitizers (PS) (benzo[a]phenothiazinium chloride and benzo[a]phenoselenazinium chloride) against Mycobacterium bovis BCG both in vitro and in a murine model of BCG-granuloma. The hypothesis being tested in this study was that cationic molecules could best interact with the negatively charged membrane of BCG as a model for mycobacterial infection. Cells in culture were incubated with various concentrations of PS and subsequently illuminated using a 635 nm diode laser. Dark- and light-induced killing profiles were generated as a function of fluence and dye concentration. In vivo, local injection of the PS into subcutaneous Mycobacterium-induced granuloma sites in murine model was followed by red light illumination of the same area. A special microscope was fabricated for real-time in vivo fluorescent microscopy to monitor EtNBS delivery to subcutaneous murine granulomata. Both PS demonstrated good in vitro antimycobacterial photodynamic activity with varying degrees of toxicity under dark conditions. Real time in vivo monitoring of benzophenothiazine chloride in the mouse model indicated that this fluorescent photosensitizer was delivered rapidly to the subcutaneous granuloma site. In vivo, photosensitizer specific dark- and photo-toxicities depended on the structure, concentration of the photosensitizer and the light dose utilized. Cationic phenothiazine photosensitizers are promising candidates for use in anti-mycobacterial PDT for localized diseases such as cutaneous and pulmonary granulomata.


The 20-core prostate biopsy as an initial strategy: impact on the detection of prostatic cancer.
To increase the detection rate of prostate cancer in recent years, we examined the increase in the number of cores taken at initial prostate biopsy. We hypothesized that an increasing number of cores may undermine the accuracy of models predicting the presence of prostate cancer at initial biopsy in patients submitted to 20-core initial biopsy. A total of 232 consecutive patients with prostate-specific antigen (PSA) between 4 and 20 ng/mL and/or abnormal digital rectal examination (DRE) underwent 12-core prostate biopsy protocol (group 1) or 20-core prostate biopsy protocol (group 2). The patients were divided into subgroups according to the results of their serum PSA and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. Clinical data were analyzed using chi-square analysis and the unpaired t-test or 1-way ANOVA with significance considered at 0.05. The 2 groups of patients were not significantly different with regard to parameters (age, abnormal DRE and serum PSA), although median prostate volume in group 1 (57.76 +/- 26.94 cc) were slighter greater than in group 2. Cancer detection rate for patients submitted to 20 prostate biopsy was higher than patients submitted to 12 prostate biopsy (35.2% vs. 25%, p = 0.095). Breakdown to PSA level showed a benefit to 20 prostate biopsy for PSA <6 ng/mL (37.1% vs. 12.9%, p = 0.005). Stratifying results by prostate volume, we found that the improvement of cancer detection rate with 20 prostate biopsy was significant in patients with a prostate volume greater than 60 cc (55% in 20 prostate biopsy vs. 11.3% p < 0.05). Morbidity rates were identical in groups 1 and 2 with no statistically significant difference. There appeared to be no greater risk of infection and bleeding with 20 prostate biopsy protocol. The 20-core biopsy protocol was more efficient than the 12-core biopsy protocol, especially in patients with prostate specific antigen <6 ng/mL and prostate volume greater than 60 cc.


Quantitative measurements of protein interactions in a crowded cellular environment.
Quantitative measurements of protein interaction strengths, crucial for describing signaling networks and predicting cellular responses to environmental stimuli, are typically performed in dilute buffer solutions. However, protein-protein interactions in cells occur within the context of a crowded system, which is characterized by a high macromolecular concentration. In this paper, we explore the utility of cell-derived vesicles as a model crowded environment for quantitative FRET measurements of protein-protein interactions. We show that the FRET efficiency, and the donor and acceptor concentrations, can be calculated in each vesicle. We also introduce the "quantitative imaging Foster resonance energy transfer" method as a tool that can yield protein interaction strengths within these vesicles.


Numerical abstraction in infants: another look.
This article examines an important finding from the literature on infant numerical competence. The finding, reported by P. Starkey, E. S. Spelke, and R. Gelman (1990), was that infants looked longer toward a visual display that was equal in number to an auditory set. In Experiment 1, when the procedures described by P. Starkey et al. were followed and duration was held constant across auditory sequences that varied in number, infants looked longer toward the display that was not numerically equivalent to the auditory set. In Experiment 2, when the rate and duration of the auditory sequences were varied randomly within infants, no significant preference for either the equivalent or nonequivalent visual display was shown. These results raise questions about P. Starkey et al.'s claims that infants can represent the numerosity of sets in different modalities and then perform one-one correspondence computations over them.


Acute type A aortic dissection in non-agenarians: to cut or not.
Surgery for acute type A aortic dissection (type AAD) in non-agenarians is usually contraindicated due to advanced age. The aim of this study was to assess and compare outcomes after surgical or conservative treatment for acute type AAD in non-agenarians by evaluating frailty. Between October 2012 and September 2018, 273 patients underwent open repair for type AAD at the Shonan Kamakura General Hospital and the Shonan Fujisawa Tokushukai Hospital, and here, we retrospectively reviewed the case reports of 10 surgically treated non-agenarians and 15 conservatively treated non-agenarians. Exclusion criteria for surgery were the patient's refusal of surgery, severe dementia and coma. In patients considered to be at a high risk, our judgements were based on the results of comprehensive evaluation. Both in-hospital mortality and 30-day mortality in the surgical group were zero, while in-hospital mortality in conservatively treated non-agenarians was 73.3%. Importantly, 1-year survival in the surgical group and conservative group was 90% and 25%, respectively. The 5-year survival in the surgical group and conservative group was 49.2% and 25%, respectively (log-rank test, P = 0.0105). Four of 6 patients with preoperative clinical frailty scores not higher than 4 were still alive at 1 year with the same level of preoperative frailty. Surgery for acute type AAD in non-agenarians can be performed with acceptable outcomes in carefully selected patients, particularly in those with preoperative clinical frailty scores not higher than 4.


Ancient mitochondrial pseudogenes reveal hybridization between distant lineages in the evolution of the Rupicapra genus.
Mitochondrial pseudogenes (numts) inserted in the nuclear genome are frequently found in population studies. Its presence is commonly connected with problems and errors when they are confounded with true mitochondrial sequences. In the opposite side, numts can provide valuable phylogenetic information when they are copies of ancient mitochondrial lineages. We show that Rupicapra individuals of different geographic origin from the Cantabrian Mountains to the Apennines and the Caucasus share a nuclear COI fragment. The numt copies are monophyletic, and their pattern of differentiation shows two outstanding features: a long evolution as differentiated true mitochondrial lineage, and a recent integration and spread through the chamois populations. The COI pseudogene is much older than the present day mitochondrial clades of Rupicapra and occupies a basal position within the Rupicapra-Ammotragus-Arabitragus node. Joint analysis of this numt and a cytb pseudogene with a similar pattern of evolution places the source mitochondrial lineage as a sister branch that separated from the Ammotragus-Arabitragus lineage 6millionyearsago (Mya). The occurrence of this sequence in the nucleus of chamois suggests hybridization between highly divergent lineages. The integration event seems to be very recent, more recent than the split of the present day mtDNA lineages of Rupicapra (1.9Mya). This observation invites to think of the spread across the genus by horizontal transfer through recent male-biased dispersal.


A Refractory Livedoid Vasculopathy Accompanied by Methylene Tetrahydrofolate Reductase Gene Polymorphism Successfully Treated with Hyperbaric Oxygen Therapy.
Livedoid vasculopathy (LV) is a chronic coagulation disorder characterized by recurrent, painful ulcers on the lower extremities. Methylene tetrahydrofolate reductase (MTHFR) gene polymorphism is associated with coagulopathy. Therapeutic options usually include anti-inflammatory or immunosuppressive agents. However, the condition is still highly challenging to manage and no consensus over the first-line treatment for LV exists. Furthermore, when LV is accompanied with MTHFR gene polymorphism, clinical presentations could be more severe and resistant to treatment. We report a case of refractory LV accompanied by MTHFR gene polymorphism, which was successfully treated with hyperbaric oxygen therapy (HBOT). A 63-year-old female patient presented with multiple painful ulcers, atrophie blanches, and retiform purpura on both lower legs and feet. Histopathologic findings were compatible with LV. LV was diagnosed based on these clinicopathological findings. Following the diagnosis, we treated the patient with pentoxifylline, aspirin, systemic corticosteroid, antihistamine, and antibiotics. In spite of six-month treatment, the skin lesions did not improve; hence, HBOT was performed. It was performed at 2.0 absolute atmosphere for 120 minutes each time, three times a week. After 4 sessions, the ulcers began to heal and after 13 sessions, the skin lesions almost healed. During the eight-month follow-up period, the skin ulcers did not recur and the symptoms remained stable. Additionally, it was confirmed that she had MTHFR gene polymorphism after a genetic test. In conclusion, we wish to provide evidence regarding the effectiveness of HBOT and suggest that HBOT might be a considerable treatment option in refractory LV.


The antiresorptive effects of a single dose of zoledronate persist for two years: a randomized, placebo-controlled trial in osteopenic postmenopausal women.
Annual iv administration of 5 mg zoledronate decreases fracture risk. The optimal dosing interval of 5 mg zoledronate is not known. Our objective was to determine the duration of antiresorptive action of a single 5-mg dose of iv zoledronate. We conducted a double-blind, randomized, placebo-controlled trial over 2 yr at an academic research center, in a volunteer sample of 50 postmenopausal women with osteopenia. Intervention included 5 mg zoledronate. Biochemical markers of bone turnover and bone mineral density of the lumbar spine, proximal femur, and total body. Compared with placebo, zoledronate treatment decreased mean levels of each of four markers of bone turnover by at least 38% (range 38-45%) for the duration of the study (P < 0.0001 for each marker). After 2 yr, bone mineral density was higher in the zoledronate group than the placebo group by an average of 5.7% (95% confidence interval = 4.0-7.4) at the lumbar spine, 3.9% (2.2-5.7) at the proximal femur, and 1.7% (0.8-2.5) at the total body (P < 0.0001 for each skeletal site). Between-groups differences in markers of bone turnover and bone mineral density were similar at 12 and 24 months. Mild secondary hyperparathyroidism was present throughout the study in the zoledronate group. The antiresorptive effects of a single 5-mg dose of zoledronate are sustained for at least 2 yr. The magnitudes of the effects on markers of bone turnover and bone mineral density are comparable at 12 and 24 months. Administration of zoledronate at intervals of up to 2 yr may be associated with antifracture efficacy; clinical trials to investigate this possibility are justified.


ConoDictor: a tool for prediction of conopeptide superfamilies.
ConoDictor is a tool that enables fast and accurate classification of conopeptides into superfamilies based on their amino acid sequence. ConoDictor combines predictions from two complementary approaches-profile hidden Markov models and generalized profiles. Results appear in a browser as tables that can be downloaded in various formats. This application is particularly valuable in view of the exponentially increasing number of conopeptides that are being identified. ConoDictor was written in Perl using the common gateway interface module with a php submission page. Sequence matching is performed with hmmsearch from HMMER 3 and ps_scan.pl from the pftools 2.3 package. ConoDictor is freely accessible at http://conco.ebc.ee.


Bladder outlet obstruction in women: difficulties in the diagnosis.
To identify the difficulties in diagnosing bladder outlet obstruction in women. 53 women with a mean age of 37.2 (range 16-70) with chronic lower urinary tract symptoms and no neurogenic or organic diseases were examined. The prevalent symptoms were frequency (96%), urgency (92%) and nocturia (75%), and the mean duration of symptoms was 3.8 years. After pressure-flow studies and voiding cystourethrography were conducted, patients either underwent bladder neck or urethral incisions based on their diagnosis. These patients were subsequently subjected to follow-up uroflow studies. Abnormal uroflow curves were observed in 19 of 53 women. In 10 of them (52.6%), bladder outlet obstruction based on pressure-flow results was confirmed. Voiding cystourethrography results from these 19 women confirmed that 17 patients had bladder neck obstruction, while the remaining 2 had urethral obstruction. 16 of 19 were treated endoscopically, with 14 patients undergoing bladder neck incisions through the 5- and 7-o'clock positions and 2 patients having a distal urethral incision through the 12-o'clock position. In all of these 16 cases, there were both a statistical increase in the maximum flow rate (Qmax) as well as an improvement in the flow curves. Symptomatic improvement was observed in 12 of the 16 women subjected to surgical intervention. Bladder outlet obstruction exists in women with lower urinary tract symptoms. Pressure-flow studies and voiding cystourethrography are reliable modalities for confirming bladder outlet obstruction. Bladder outlet obstruction can be functionally or structurally caused.


Young Adults on the Autism Spectrum and Early Employment-Related Experiences: Aspirations and Obstacles.
In the United States, employment outcomes for young adults with an autism spectrum disorder (ASD) are poor, with many unemployed, underemployed, or otherwise unable to achieve their potential regardless of cognitive ability. To explore employment expectations and experiences, qualitative interviews were conducted with 12 young adults with ASD and 28 parents. Transcripts were analyzed using the constant comparative method associated with a grounded theory approach. Three major themes emerged: Employment Aspirations and Potential, Challenges of Job Finding and Keeping, and Differing Parent and Young Adult Work-Related Roles and Views. Issues discussed include the need to foster meaningful pre-employment opportunities, acknowledge the role of families in employment issues, provide ASD-focused workplace support, and effectively coordinate intersecting systems (e.g., schools, agencies, employers).


[Therapeutic impact of streptococcal and enterococcal bacteremia in hematology patients].
From January 1999 to May 2000 (17 months), 21 strains of streptococci and four strains of enterococci have been isolated from 74 blood cultures in 25 infectious episodes in hematologic patients. They concerned 21 patients, of 21 to 77 years old. These patients suffered from acute leukaemia (14 cases), chronic lymphoid leukaemia (two cases), non-Hodgkin's lymphoma (two cases) or myeloma (three cases). Seventeen patients displayed a single streptococcal or enterococcal episode, two had two episodes in the course of a single stay in the hospital, two others in the course of two different stays. During 16 episodes (64%), the bacteremia occurred within 15 days after the onset of neutropenia consecutive to antimitotic chemotherapy, and in nine episodes (36%) it has occurred after a period exceeding 15 days. In six cases the patients had already received antibiotics with a large antibacterial activity (beta-lactam, fluoroquinolone and/or glycopeptide +/- aminoside) and in four cases a single antibiotic (synergistine or cotrimoxazole). Most streptococci (20/21) were oral streptococci (ten Streptococcus mitis, five S. oralis, two S. sanguis, three S. pneumoniae). A single strain of beta-hemolytic streptococci has been identified as S. dysgalactiae subsp. equisimilis. The enterococci were one strain of Enterococcus faecalis and three E. faecium. Ten streptococci were susceptible to 0.25 mg/L of penicillin G, ten were less susceptible (0.5 < or = MIC < 32 mg/L), and a strain was resistant (MIC = 32 mg/L). Eighteen strains were susceptible to amoxicillin and cefotaxime. For three strains, the MICs of amoxicillin and cefotaxime (8-16 mg/L and 8-32 mg/L, respectively) were higher. Levels of resistance of the enterococci to the beta-lactam (penicillin, amoxicillin, and piperacillin) were variable. All species were susceptible to glycopeptides. Three patients were transferred in intensive care unit for respiratory distress or shock syndrome. Their evolution has remained severe under antibiotherapy comprising beta-lactam or vancomycin associated with an aminoside. This results demonstrate the interest of species identification to adapt the antibiotic treatment and confirms the frequency of oral streptococci in severe bacteremia in neutropenic patients.


Endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations.
This study was undertaken to prospectively evaluate the efficacy and safety of endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations. Surgical therapy has been the traditional approach to large or unresolving biliary fistulas complicating liver transplantation. Although endoscopic management is rapidly becoming an acceptable alternative to surgery for the treatment of biliary fistulas complicating non-liver transplant hepatobiliary operations, it has received limited attention in the liver transplant setting. During a 15-month period, 146 adults underwent liver transplantation with biliary reconstruction by end-to-end choledochocholedochostomy over a T-tube. Inadvertent T-tube migration or intentional T-tube removal resulted in bile peritonitis in 18 patients. The patients were treated with a nasobiliary tube (n = 13), internal stent plus endoscopic sphincterotomy (n = 3), or internal stent alone (n = 2). Thirteen patients had a biliary fistula after other hepatobiliary operations and underwent endoscopic therapy during a similar period. All 13 had an endoscopic sphincterotomy with removal of obstructing stones when present (n = 6). Twelve patients also had stents placed. All patients were prospectively followed after hospital discharge and assessed for recurrent symptoms suggestive of biliary tract disease and procedure-related complications. Endoscopic retrograde cholangiopancreatography (ERCP) identified a biliary fistula at the T-tube insertion site into the bile duct in all 18 liver transplant patients. Seventeen patients had resolution of their symptoms within 12 hours of therapy. The fistula sealed in 94.4%. In the other hepatobiliary operation group, ERCP demonstrated contrast extravasation from the biliary tree in 12 of 13. The biliary fistula closure rate was 92.3%. The endoscopic complication rate for the two groups was 3.2%. During a mean follow-up of 9 months, recurrent biliary tract complications occurred in 11.1% of the liver transplant group and 0% in the other hepatobiliary operation group (p > 0.05). The 30-day mortality rate was 0%. The results of this study support the application of endoscopic management of biliary fistulas complicating orthotopic liver transplantation and other hepatobiliary operations. This approach was relatively safe and obviated the need for surgical intervention.


Varestrongylus eleguneniensis sp. n. (Nematoda: Protostrongylidae): a widespread, multi-host lungworm of wild North American ungulates, with an emended diagnosis for the genus and explorations of biogeography.
A putative new species of Varestrongylus has been recently recognized in wild North American ungulates based on the ITS-2 sequences of larvae isolated from feces during a wide geographic survey. No taxonomic description was provided, as adult specimens were not examined. Lungworm specimens were collected in the terminal bronchioles of muskoxen from Quebec, and a woodland caribou from central Alberta, Canada. The L3 stage was recovered from experimentally infected slugs (Deroceras spp.). Description of specimens was based on comparative morphology and integrated approaches. Molecular identity was determined by PCR and sequencing of the ITS-2 region of the nuclear ribosomal DNA, and compared to other protostrongylids. Varestrongylus eleguneniensis sp. n. is established for a recently discovered protostrongylid nematode found in caribou (Rangifer tarandus), muskoxen (Ovibos moschatus) and moose (Alces americanus); hosts that collectively occupy an extensive geographic range across northern North America. Adults of Varestrongylus eleguneniensis are distinguished from congeners by a combination of characters in males (distally bifurcate gubernaculum, relatively short equal spicules not split distally, a strongly elongate and bifurcate dorsal ray, and an undivided copulatory bursa) and females (reduced provagina with hood-like fold extending ventrally across prominent genital protuberance). Third-stage larvae resemble those found among other species in the genus. The genus Varestrongylus is emended to account for the structure of the dorsal ray characteristic of V. eleguneniensis, V. alpenae, V. alces and V. longispiculatus. Herein we describe and name V. eleguneniensis, a pulmonary protostrongylid with Rangifer tarandus as a primary definitive host, and which secondarily infects muskoxen and moose in areas of sympatry. Biogeographic history for V. eleguneniensis and V. alpenae, the only two endemic species of Varestrongylus known from North America, appears consistent with independent events of geographic expansion with cervid hosts from Eurasia into North America during the late Pliocene and Quaternary.


Spider Silk Protein Forms Amyloid-Like Nanofibrils through a Non-Nucleation-Dependent Polymerization Mechanism.
Amyloid fibrils-nanoscale fibrillar aggregates with high levels of order-are pathogenic in some today incurable human diseases; however, there are also many physiologically functioning amyloids in nature. The process of amyloid formation is typically nucleation-elongation-dependent, as exemplified by the pathogenic amyloid-β peptide (Aβ) that is associated with Alzheimer's disease. Spider silk, one of the toughest biomaterials, shares characteristics with amyloid. In this study, it is shown that forming amyloid-like nanofibrils is an inherent property preserved by various spider silk proteins (spidroins). Both spidroins and Aβ capped by spidroin N- and C-terminal domains, can assemble into macroscopic spider silk-like fibers that consist of straight nanofibrils parallel to the fiber axis as observed in native spider silk. While Aβ forms amyloid nanofibrils through a nucleation-dependent pathway and exhibits strong cytotoxicity and seeding effects, spidroins spontaneously and rapidly form amyloid-like nanofibrils via a non-nucleation-dependent polymerization pathway that involves lateral packing of fibrils. Spidroin nanofibrils share amyloid-like properties but lack strong cytotoxicity and the ability to self-seed or cross-seed human amyloidogenic peptides. These results suggest that spidroins´ unique primary structures have evolved to allow functional properties of amyloid, and at the same time direct their fibrillization pathways to avoid formation of cytotoxic intermediates.


Cancer screening. Degrees of proof and practical application.
The purpose of this paper is to clarify the short-term and long-term objectives of screening for various cancers, and to indicate the kinds of data that are needed to determine whether or not the objectives are met. Cancers at various sites differ with respect to their innate suitability for screening. Criteria that enhance screening suitability include the potential for serious complications and a high rate of mortality (applicable to most cancers), a prolonged preclinical phase, and an existing therapy that is simpler and more effective in reducing the mortality rate when applied to preclinical disease than to clinically evident cancer. Tests and procedures suitable for screening are simple to perform, inexpensive, acceptable to patients and physicians, safe, relatively painless, and accurate, as measured by the test's sensitivity and specificity. The actual yield of previously undiagnosed cancer arising from a screening program will depend heavily on prevalence of disease in the screened population, specificity of the screening test, and successful follow-up of screen-positive patients with diagnosis and treatment. These issues are discussed in the context of four cancers and their respective screening modalities: cervical cancer and cytologic studies, breast cancer and mammography, colon cancer and fecal occult blood tests, and lung cancer and sputum cytologic studies. The quality of data on which screening decisions have been made for each of these cancers and tests varies. The cancers vary in terms of their relevant biologic characteristics and treatment effectiveness. Similarly, each screening procedure has its own particular advantages and disadvantages. Current American Cancer Society Guidelines for early detection of three of the cancers are presented.


Documentation of Spontaneous Macular Hole Closure in Macular Telangiectasia Type 2 Using Multimodal Imaging.
Macular holes in the setting of macular telangiectasia type 2 can be difficult to manage. The rates of anatomical closure after macular hole surgery are less favorable in patients with macular telangiectasia than in those with idiopathic macular holes. These differences may be due to the influence of unique pathogenic mechanisms that modulate macular hole dynamics in patients with macular telangiectasia. In this report, the authors document the multimodal imaging findings of a patient with macular telangiectasia demonstrating spontaneous macular hole closure. These findings may improve the understanding of the natural course of this entity and may have relevance for clinical management.


Acid phosphatase activity in lymphocytes from patients with Spielmeyer-Vogt-Batten's syndrome.
The purpose of the investigation presented was to study whether the lymphocytes from patients with Spielmeyer-Vogt-Batten's syndrome deviate from normal with respect to acid phosphatase activity. The distribution of the activity seems to show that the patients with Spielmeyer-Vogt-Batten's syndrome can be divided into two groups, viz. one in which the values are concentrated around the normal level, and another with increased values.


Closed-Loop Multitarget Optimization for Discovery of New Emulsion Polymerization Recipes.
Self-optimization of chemical reactions enables faster optimization of reaction conditions or discovery of molecules with required target properties. The technology of self-optimization has been expanded to discovery of new process recipes for manufacture of complex functional products. A new machine-learning algorithm, specifically designed for multiobjective target optimization with an explicit aim to minimize the number of "expensive" experiments, guides the discovery process. This "black-box" approach assumes no a priori knowledge of chemical system and hence particularly suited to rapid development of processes to manufacture specialist low-volume, high-value products. The approach was demonstrated in discovery of process recipes for a semibatch emulsion copolymerization, targeting a specific particle size and full conversion.


Colorado revised statutes in support of palliative care limiting criminal liability.
Colorado's manslaughter law classifies assisted suicide as a felony. Because terminal patients are close to life's end, death while being treated is inevitable, therefore, there was concern among physicians that the fear of prosecution continued to prevent adequate pain relief for terminal patients. A group of physicians and concerned citizens set out to amend Colorado Revised Statutes to reassure doctors and others prescribing or administering palliative care for terminal patients that they would not be indicted under the law prohibiting assisted suicide. The 2006 Assembly passed the amendment (quoted in the text) with virtually no opposition in either house and it was signed into law by the governor, effective July 6, 2006. Note that in addition to allowing appropriate pain management, it specifically emphasizes that it does not permit assisted suicide.


The Role of Paternal Involvement on Behavioral Sensitive Responses and Neurobiological Activations in Fathers: A Systematic Review.
As fathering research has flourished, a growing body of studies has focused on behavioral and neurobiological mechanisms, respectively associated with caregiving sensitivity and responsiveness to infant stimuli. However, the association between these aspects and the key concept of paternal involvement in childcare (i.e., contribution in infant care in terms of time, availability, and responsibility) has been poorly investigated. The current work aims to systematically review the role of involvement in childcare on both neural activations and sensitive behaviors in fathers by examining (a) how paternal involvement has been measured and (b) whether paternal involvement has been associated with neurobiological activation and behavioral sensitive responses. Inclusion criteria were peer-reviewed quantitative studies, concerning fathers responding to infant stimuli at neurobiological or behavioral level, and including a quantitative measurement of paternal involvement in childcare. A quality rating for each study has been performed based on the measurements adopted to assess paternal involvement. Of 2,529 articles, 27 studies were included. According to our quality rating, 10 out of 27 studies included fairly good-standard measures for measuring paternal involvement, whereas 17 studies used good-standard measures. In addition, 11 studies provided details of paternal involvement in the context of neurobiological responses to infant stimuli, whereas 16 addressed paternal sensitive behaviors. Overall, only 8 studies reported relevant findings about the relationship between paternal involvement and neurobiological responses or sensitive behaviors in fathers. The present study is the first systematically evaluating the scope of paternal involvement in the field of Paternal Brain and fathers' sensitive responsiveness research. When high-standard measures are used, paternal involvement seems to play a significant role in modulating both the hormonal and the neural pathways associated with paternal behaviors. Remarkably, the role of paternal engagement may underpin an adaptive nurturance that is not dependent on pregnancy and childbirth but on caregiving experience. A promising positive link between paternal involvement and behavioral sensitivity may be expected in further studies, which will need to corroborate our conclusion by adopting detailed and appropriate measures assessing paternal involvement. As a future line of research, the inclusion of gay fathers may be beneficial for the field.


Effects of nine weeks L-Carnitine supplementation on exercise performance, anaerobic power, and exercise-induced oxidative stress in resistance-trained males.
Studies of L-carnitine in healthy athletic populations have yielded equivocal results. Further scientific-based knowledge is needed to clarify the ability of L-carnitine to improve exercise capacity and expedite the recovery process by reducing oxidative stress. This study aimed to examine the 9-week effects of L-carnitine supplementation on exercise performance, anaerobic capacity, and exercise-induced oxidative stress markers in resistance-trained males. In a double-blind, randomized, and placebo-controlled treatment, 23 men (age, 25±2y; weight, 81.2±8.31 kg; body fat, 17.1±5.9%) ingested either a placebo (2 g/d, n=11) or L-carnitine (2 g/d, n=12) for 9 weeks in conjunction with resistance training. Primary outcome measurements were analyzed at baseline and at weeks 3, 6, and 9. Participants underwent a similar resistance training (4 d/w, upper/lower body split) for a 9-week period. Two-way ANOVA with repeated measures was used for statistical analysis. There were significant increases in bench press lifting volume at wk-6 (146 kg, 95% CI 21.1, 272) and wk-9 (245 kg, 95% CI 127, 362) with L-carnitine. A similar trend was observed for leg press. In the L-carnitine group, at wk-9, there were significant increases in mean power (63.4 W, 95% CI 32.0, 94.8) and peak power (239 W, 95% CI 86.6, 392), reduction in post-exercise blood lactate levels (-1.60 mmol/L, 95% CI -2.44, -0.75) and beneficial changes in total antioxidant capacity (0.18 mmol/L, 95% CI 0.07, 0.28). L-carnitine supplementation enhances exercise performance while attenuating blood lactate and oxidative stress responses to resistance training.


Slow-release drug delivery through Elvax 40W to the rat retina: implications for the treatment of chronic conditions.
Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these diseases. Chronic retinal diseases such as retinal oedema or neovascularization usually require multiple intraocular injections to effectively treat the condition. However, the risks associated with these injections increase with repeated delivery of the drug. Therefore, alternative delivery methods need to be established in order to minimize the risks of reinjection. Several other investigations have developed methods to deliver drugs over extended time, through materials capable of releasing chemicals slowly into the eye. In this investigation, we outline the use of Elvax 40W, a copolymer resin, to act as a vehicle for drug delivery to the adult rat retina. The resin is made and loaded with the drug. The drug-resin complex is then implanted into the vitreous cavity, where it will slowly release the drug over time. This method was tested using 2-amino-4-phosphonobutyrate (APB), a glutamate analogue that blocks the light response of the retina. It was demonstrated that the APB was slowly released from the resin, and was able to block the retinal response by 7 days after implantation. This indicates that slow-release drug delivery using this copolymer resin is effective for treating the retina, and could be used therapeutically with further testing.


Comparison of intramuscular methylergometrine, rectal misoprostol, and low-dose intravenous oxytocin in active management of the third stage of labor.
Active management of the third stage of labor (AMTSL) is a critical intervention for the prevention of postpartum hemorrhage (PPH), which is still the most common cause of maternal morbidity and mortality worldwide. The objective of the study is to compare the effect of intramuscular methylergometrine, rectal misoprostol, and low-dose intravenous oxytocin in the AMTSL in terms of amount of blood loss and duration of the third stage of labor, cost-effectiveness, and side effect profile. Seventy-five pregnant patients admitted in the maternity ward for vaginal delivery from February 2017 to February 2018 received either intramuscular methylergometrine (0.2 mg) or rectal misoprostol (400 mcg) or low-dose intravenous oxytocin (5 units oxytocin in 100 mL normal saline) for AMTSL. Data were recorded in three groups: Group A (methylergometrine), Group B (misoprostol), and Group C (oxytocin) consisting of 25 cases each. Mean blood loss was found to be least in methylergometrine group (246.87 ± 65.44 mL) as compared to misoprostol (346.13 ± 58.35 mL) and oxytocin (334.5 ± 69.20 mL) (P = 0.000) Mean duration of the third stage of labor was also least in methylergometrine group (6.21 ± 1.58 min) (P = 0.0008). Although methylergometrine was found to have higher incidence of side effects such as nausea, vomiting, headache, and raised blood pressure, it was found to be the most effective drug for minimizing blood loss in the third stage of labor. In remote places where healthcare facilities are limited and drugs cannot be administered by parenteral route, rectal misoprostol remains an alternative.


Evaluation of Vehicle-Based Crash Severity Metrics.
Vehicle change in velocity (delta-v) is a widely used crash severity metric used to estimate occupant injury risk. Despite its widespread use, delta-v has several limitations. Of most concern, delta-v is a vehicle-based metric which does not consider the crash pulse or the performance of occupant restraints, e.g. seatbelts and airbags. Such criticisms have prompted the search for alternative impact severity metrics based upon vehicle kinematics. The purpose of this study was to assess the ability of the occupant impact velocity (OIV), acceleration severity index (ASI), vehicle pulse index (VPI), and maximum delta-v (delta-v) to predict serious injury in real world crashes. The study was based on the analysis of event data recorders (EDRs) downloaded from the National Automotive Sampling System / Crashworthiness Data System (NASS-CDS) 2000-2013 cases. All vehicles in the sample were GM passenger cars and light trucks involved in a frontal collision. Rollover crashes were excluded. Vehicles were restricted to single-event crashes that caused an airbag deployment. All EDR data were checked for a successful, completed recording of the event and that the crash pulse was complete. The maximum abbreviated injury scale (MAIS) was used to describe occupant injury outcome. Drivers were categorized into either non-seriously injured group (MAIS2-) or seriously injured group (MAIS3+), based on the severity of any injuries to the thorax, abdomen, and spine. ASI and OIV were calculated according to the Manual for Assessing Safety Hardware. VPI was calculated according to ISO/TR 12353-3, with vehicle-specific parameters determined from U.S. New Car Assessment Program crash tests. Using binary logistic regression, the cumulative probability of injury risk was determined for each metric and assessed for statistical significance, goodness-of-fit, and prediction accuracy. The dataset included 102,744 vehicles. A Wald chi-square test showed each vehicle-based crash severity metric estimate to be a significant predictor in the model (p < 0.05). For the belted drivers, both OIV and VPI were significantly better predictors of serious injury than delta-v (p < 0.05). For the unbelted drivers, there was no statistically significant difference between delta-v, OIV, VPI, and ASI. The broad findings of this study suggest it is feasible to improve injury prediction if we consider adding restraint performance to classic measures, e.g. delta-v. Applications, such as advanced automatic crash notification, should consider the use of different metrics for belted versus unbelted occupants.


Prospective study of Clostridium difficile colonization and paracresol detection in the stools of babies on a special care unit.
Infants' stools were examined for the presence of Clostridium difficile and its cytotoxin in a study performed over a one-year period on a special care baby unit. Overall, 21% of infants were colonized, but the organism was only recovered in a seven-month period during which its weekly prevalence in the group varied from zero to 44%, with a distinct clustering of colonized infants being observed. Tests for the presence of cytotoxin in the stools and in supernatants of broth that had been inoculated with each isolate were negative. The factors predisposing to colonization were a prolonged stay in the unit, low birth weight, younger gestational age and being nursed in an incubator. The organism was recovered only once from an environmental screen. An antibiogram, used in conjunction with toxin production, was helpful in distinguishing these isolates from a collection obtained from other units in the hospital. We conclude that Cl. difficile was acquired by nosocomial spread although we did not establish the precise mechanism involved. The detection of para-cresol by gas-liquid chromatography was found to be specific but insufficiently sensitive as a screening test for the organism's presence in the stools. It could only be demonstrated in infants whose birth-weights were less than 2500 g, and no association was observed between the type of feed and para-cresol presence in stools.


Root morphology of mandibular premolars in 40 patients with Turner syndrome.
To analyse root morphology of mandibular premolars in 40 females with Turner syndrome. All patients aged 18-50 years (mean+/-SD: 26.2+/-6.22) were clinically and cytogenetically diagnosed and divided into three groups according to karyotype: I-with 45,X (n=19); II-with 46,X,i(Xq) and other structural changes of this chromosome (n=8); III-with mos45,X/46,XX and other mosaic karyotype (n=13). The control group consisted of 30 healthy women aged 20-50 years (mean+/-SD: 31.52+/-5.21) who underwent dental treatment at the Department of Conservative Dentistry and Department of Periodontology and Oral Mucosa Diseases, Medical University of Gdańsk, Poland. The root morphology of mandibular premolars was studied based on orthopantomogram X-ray images. The results were analysed using chi-square test with Yates's adjustment. Separate mesial and distal root canals and separate root apices were noted on orthopantomograms in patients with Turner syndrome. Two-rooted mandibular first premolars were observed in 34% of cases in group 45,X (group I), in 31% of cases in the group with structural aberrations of chromosome X (group II) and in 31% of cases with mosaic karyotypes (group III). Two-rooted mandibular second premolars were observed in 39% cases in group 45,X and in 31% of cases in the group with structural aberrations of chromosome X and in 35% of cases with mosaic karyotypes. This type of root morphology was not observed in the control group. No significant difference was found between the three groups of Turner syndrome. Highly significant differences in root morphology of mandibular premolars between patients with Turner syndrome and a population control group were found.


Solitary fibrous tumor of the orbit in a child.
Solitary fibrous tumor is a rare spindle-cell tumor that usually is seen in the pleura. The orbit is one of the most common extrapleural sites. It is frequently misdiagnosed as hemangiopericytoma and is seen in older patients. We present the youngest case of this tumor, which was apparent in family photographs by age 10 and removed at age 15. The first reported echography findings are presented. Case report and literature review. Solitary fibrous tumor was diagnosed by microscopy and immunohistochemical study that showed cells reactive with vimentin and CD34. Solitary fibrous tumor of the orbit has been diagnosed with increasing frequency in recent years as the result of improved methods of pathologic examination. It is important to be aware of this tumor and recognize that it must be included in the differential diagnosis of highly vascular spindle-cell tumors even in young children.


Regulatory Cues in Pulmonary Fibrosis-With Emphasis on the AIM2 Inflammasome.
Pulmonary fibrosis (PF) is a chronic lung disorder characterized by the presence of scarred and thickened lung tissues. Although the Food and Drug Administration approved two antifibrotic drugs, pirfenidone, and nintedanib, that are currently utilized for treating idiopathic PF (IPF), the clinical therapeutic efficacy remains unsatisfactory. It is crucial to develop new drugs or treatment schemes that combine pirfenidone or nintedanib to achieve more effective outcomes for PF patients. Understanding the complex mechanisms underlying PF could potentially facilitate drug discovery. Previous studies have found that the activation of inflammasomes, including nucleotide-binding and oligomerization domain (NOD)-like receptor protein (NLRP)1, NLRP3, NOD-like receptor C4, and absent in melanoma (AIM)2, contributes to lung inflammation and fibrosis. This article aims to summarize the cellular and molecular regulatory cues that contribute to PF with a particular emphasis on the role of AIM2 inflammasome in mediating pathophysiologic events during PF development. The insights gained from this research may pave the way for the development of more effective strategies for the prevention and treatment of PF.


Applications of crowdsourcing in health: an overview.
Crowdsourcing is a nascent phenomenon that has grown exponentially since it was coined in 2006. It involves a large group of people solving a problem or completing a task for an individual or, more commonly, for an organisation. While the field of crowdsourcing has developed more quickly in information technology, it has great promise in health applications. This review examines uses of crowdsourcing in global health and health, broadly. Semantic searches were run in Google Scholar for "crowdsourcing," "crowdsourcing and health," and similar terms. 996 articles were retrieved and all abstracts were scanned. 285 articles related to health. This review provides a narrative overview of the articles identified. Eight areas where crowdsourcing has been used in health were identified: diagnosis; surveillance; nutrition; public health and environment; education; genetics; psychology; and, general medicine/other. Many studies reported crowdsourcing being used in a diagnostic or surveillance capacity. Crowdsourcing has been widely used across medical disciplines; however, it is important for future work using crowdsourcing to consider the appropriateness of the crowd being used to ensure the crowd is capable and has the adequate knowledge for the task at hand. Gamification of tasks seems to improve accuracy; other innovative methods of analysis including introducing thresholds and measures of trustworthiness should be considered. Crowdsourcing is a new field that has been widely used and is innovative and adaptable. With the exception of surveillance applications that are used in emergency and disaster situations, most uses of crowdsourcing have only been used as pilots. These exceptions demonstrate that it is possible to take crowdsourcing applications to scale. Crowdsourcing has the potential to provide more accessible health care to more communities and individuals rapidly and to lower costs of care.


Bacterial profile and antimicrobial resistance patterns of infected diabetic foot ulcers in sub-Saharan Africa: a systematic review and meta-analysis.
The number of diabetic foot ulcer patients is substantially increasing, with the rapidly rising burden of diabetic mellitus in sub-Saharan Africa. The data on the regional prevalence of diabetic foot ulcer infecting bacteria and their antimicrobial resistance patterns is crucial for its proper management. This systematic review and meta-analysis determined the pooled prevalence of bacterial profiles and antimicrobial resistance patterns of infected diabetic foot ulcers in sub-Saharan Africa. A comprehensive search of the literature was performed on CINAHL, EMBASE, Google Scholar, PubMed, Scopus, and Web of Science databases. Critical appraisal was done using the Joanna Briggs Institute's tool for prevalence studies. A pooled statistical meta-analysis was conducted using STATA Version 17.0. The I2 statistics and Egger's test were used to assess the heterogeneity and publication bias. The pooled prevalence and the corresponding 95% confidence interval of bacterial profiles and their antimicrobial resistance patterns were estimated using a random effect model. Eleven studies with a total of 1174 study participants and 1701 bacteria isolates were included. The pooled prevalence of the most common bacterial isolates obtained from DFU were S. aureus (34.34%), E. coli (21.16%), and P. aeruginosa (20.98%). The highest pooled resistance pattern of S. aureus was towards Gentamicin (57.96%) and Ciprofloxacin (52.45%). E.coli and K. Pneumoniae showed more than a 50% resistance rate for the most common antibiotics tested. Both gram-positive and gram-negative bacteria were associated with diabetic foot ulcers in sub-Saharan Africa. Our findings are important for planning treatment with the appropriate antibiotics in the region. The high antimicrobial resistance prevalence rate indicates the need for context-specific effective strategies aimed at infection prevention and evidence-based alternative therapies.


HP30-2, a mitochondrial PRAT protein for import of signal sequence-less precursor proteins in Arabidopsis thaliana.
Chloroplasts and mitochondria contain a family of putative preprotein and amino acid transporters designated PRAT. Here, we analyzed the role of two previously characterized PRAT protein family members, encoded by At3g49560 (HP30) and At5g24650 (HP30-2), in planta using a combination of genetic, cell biological and biochemical approaches. Expression studies and green fluorescent protein tagging identified HP30-2 both in chloroplasts and mitochondria, whereas HP30 was located exclusively in chloroplasts. Biochemical evidence was obtained for an association of mitochondrial HP30-2 with two distinct protein complexes, one containing the inner membrane translocase TIM22 and the other containing an alternative NAD(P)H dehydrogenase subunit (NDC1) implicated in a respiratory complex 1-like electron transport chain. Through its association with TIM22, HP30-2 is involved in the uptake of carrier proteins and other, hydrophobic membrane proteins lacking cleavable NH2 -terminal presequences, whereas HP30-2's interaction with NDC1 may permit controlling mitochondrial biogenesis and activity.


Carbohydrate stress affecting fruitlet abscission and expression of genes related to auxin signal transduction pathway in litchi.
Auxin, a vital plant hormone, regulates a variety of physiological and developmental processes. It is involved in fruit abscission through transcriptional regulation of many auxin-related genes, including early auxin responsive genes (i.e., auxin/indole-3-acetic acid (AUX/IAA), Gretchen Hagen3 (GH3) and small auxin upregulated (SAUR)) and auxin response factors (ARF), which have been well characterized in many plants. In this study, totally five auxin-related genes, including one AUX/IAA (LcAUX/IAA1), one GH3 (LcGH3.1), one SAUR (LcSAUR1) and two ARFs (LcARF1 and LcARF2), were isolated and characterized from litchi fruit. LcAUX/IAA1, LcGH3.1, LcSAUR1, LcARF1 and LcARF2 contain open reading frames (ORFs) encoding polypeptides of 203, 613, 142, 792 and 832 amino acids, respectively, with their corresponding molecular weights of 22.67, 69.20, 11.40, 88.20 and 93.16 kDa. Expression of these genes was investigated under the treatment of girdling plus defoliation which aggravated litchi fruitlet abscission due to the blockage of carbohydrates transport and the reduction of endogenous IAA content. Results showed that transcript levels of LcAUX/IAA1, LcGH3.1 and LcSAUR1 mRNAs were increased after the treatment in abscission zone (AZ) and other tissues, in contrast to the decreasing accumulation of LcARF1 mRNA, suggesting that LcAUX/IAA1, LcSAUR1 and LcARF1 may play more important roles in abscission. Our results provide new insight into the process of fruitlet abscission induced by carbohydrate stress and broaden our understanding of the auxin signal transduction pathway in this process at the molecular level.


Influence of Renin-Angiotensin System Inhibitors on Lower-Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.
To determine whether ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) protect against lower-respiratory tract infections complicating type 2 diabetes. Of 1,732 participants with diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II (FDS2) between 2008 and 2011, 1,482 had confirmed type 2 diabetes (mean age 65.8 years and median diabetes duration 9.0 years; 51.6% were male). All were followed for hospitalizations for or with, or deaths from, pneumonia/influenza, ascertained from validated administrative data linkage from study entry to end of 2016. Cox regression and competing risk regression were used to identify independent predictors of this outcome. Two-thirds of participants (n = 982) were taking an ACEi and/or ARB at study entry (498 [33.6%] ACEi, 408 [27.5%] ARB, 76 [5.1%] both). During 9,511 person-years of follow-up (mean ± SD 6.4 ± 2.0 years), 174 participants had incident pneumonia/influenza (156 hospitalizations and 18 deaths without hospitalization). In Cox regression analysis, baseline ACEi/ARB use was independently associated with a reduced risk of incident pneumonia/influenza (cause-specific hazard ratio [HR] 0.64 [95% CI 0.45, 0.89], P = 0.008). Allowing for the competing risk of death did not change this finding (subdistribution HR 0.67 [0.48, 0.95], P = 0.024), and similar reductions were seen for ACEi, ARB alone, and ACEi/ARB combination therapy. There was no significant change in use of ACEi/ARB during follow-up [interaction with ln(time), P = 0.70]. Other significant predictors of incident pneumonia/influenza were previously reported, clinically plausible variables. ACEi/ARB reduce the risk of pneumonia/influenza in people with type 2 diabetes.


Thyroid microcarcinoma: prevalence, prognosis, and management.
To review the usual course of thyroid microcarcinoma (TMC) and the associated prognosis and treatment of affected patients. We discuss predisposing factors in the formation of TMC and the modulation of its behavior, diagnostic evaluation, and management options. TMC, generally defined as a well-differentiated thyroid cancer less than or equal to 15 mm in diameter, has an estimated prevalence (based on autopsy studies) of about 5 to 10%. Studies, however, have shown that most of these cancers are smaller than 5 mm in diameter. The high prevalence of TMC in the general population contrasts with the rarity of thyroid cancers of greater size, which constitute less than 1% of malignant neoplasms in the United States. The frequent detection of TMC as a result of routine imaging of the neck for unrelated reasons and as a incidental finding in surgical specimens has raised a question about whether the management of TMC should differ from that for thyroid cancer of appreciable size. The uncertainty about optimal management of TMC is attributable to the small number of long-term follow-up studies as well as the common observation that patients usually have an excellent prognosis. Although in most patients harboring a TMC the cancer remains quiescent and never becomes clinically significant, in some cases TMC can demonstrate an aggressive course. Several variables, such as older age, multifocality, bilateral disease, and extrathyroidal spread at initial assessment, may have some adverse prognostic significance. After a partial surgical removal of the thyroid gland for TMC, the recurrence rate may be as high as 11%. Therefore, a treatment dilemma is caused by the low propensity of TMC for progression to clinically significant disease, yet the potential for recurrence and aggressive behavior in some cases. In general, surgical resection of TMC is based on results of fine-needle aspiration biopsy and the rate of growth of the nodule. Aggressive management seems indicated in high-risk patients, particularly older patients, those with a history of radiation exposure, and those with multifocal disease, bilateral disease, or lymph node involvement.


Production of hydroxyl free radical in the xanthine oxidase system with addition of 1-methyl-3-nitro-1-nitrosoguanidine.
We have examined the mechanism of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG)-induced gastric cancer with respect to the production of hydroxyl free radical (OH). Nucleophilic attack by H2O2 on the nitroso group of MNNG produces 1-methyl-3-nitroguanidine (MNG) and the intermediate peroxynitric acid (ONOOH), which splits into hydroxyl free radical (OH) and nitrogen dioxide leading to the formation of nitric and nitrate ions in water. Xanthine oxidase (XO) induces the production of O2.- or H2O2 from molecular oxygen, depending on the overall level of enzyme reduction. In this study, we examined OH production by the reaction of MNNG with H2O2 derived from the XO-HX system containing XO and the purine substrate hypoxanthine by ESR using the spin trapping reagent 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). OH was produced in the XO-HX-DMPO system with addition of MNNG (the MNNG-XO-HX-DMPO system) under aerobic conditions, but was not in the XO-HX-DMPO system, and production of OH was inhibited by catalase but not by superoxide dismutase, suggesting that OH was produced by the reaction of MNNG with H2O2 derived from the XO-HX system. The production of OH was significantly increased with increase in the reducing activity of XO, though that of O2.- was not, also suggesting the O2(.-)-independent .OH production. The productions of nitrite ion and MNG in the MNNG-XO-HX system were determined by the colorimetric method and HPLC, respectively. Based on these findings, we conclude that .OH was produced by homolytic split of the intermediate ONOOH formed by nucleophilic attack of H2O2 derived from the XO-HX system on MNNG.


Sensitivity and specificity of magnetic resonance imaging for knee injury and clinical application for the Naresuan University Hospital.
The accuracy of MRI evaluation for the traumatic knee injury may help the physician selecting the treatment options and informing patient about the prognosis. The purpose of the present study was to analyze the result of the MRI reported from a center in Phitsanulok which would be valuable for orthopaedic surgeons who practicing in the lower northern region of Thailand. The 1.5 Tesla MRI of 51 injured knees that underwent subsequent arthroscopic knee surgery was independently reviewed by one from the group of radiologists. The sensitivity, specificity accuracy and negative predictive value of the MRI evaluation for menisci and cruciate ligament pathology compared to the arthroscopic finding is determined. There were 50 patients with the mean age of 36.7 year old (ranging from 18-75 years) and 30 were males and 20 were females. The sensitivity, specificity accuracy and negative predictive value (NPV) in detecting the complete tear of the ACL injury were 90.9%, 84.6%, 88.6% and 84.6%, respectively. There were 100%, 97.1%, 97.5% and 100%, respectively, for diagnosis of complete PCL tear. The MRI evaluation for definite medial meniscus tear revealed 100% in sensitivity, 52.6% in specificity, 64% in accuracy and 100% in NPV. For the lateral meniscus, it yielded 55.6%, 83.3%, 75.8% and 83.3%, respectively. Among the 22 patients who underwent the ACL reconstruction without the PCL or collateral ligament injury, there was 50% of associated meniscal injury with similar ratio between medial and lateral side. The MRI report from the center in Phitsanulok could be useful in detecting the cruciate ligament tear particularly with uncertain clinical examination. With a high negative predictive value, the MRI could be used as a negative diagnostic tool for the meniscal injury.


Effects of adult temperature on gene expression in a butterfly: identifying pathways associated with thermal acclimation.
Phenotypic plasticity is a pervasive property of all organisms and considered to be of key importance for dealing with environmental variation. Plastic responses to temperature, which is one of the most important ecological factors, have received much attention over recent decades. A recurrent pattern of temperature-induced adaptive plasticity includes increased heat tolerance after exposure to warmer temperatures and increased cold tolerance after exposure to cooler temperatures. However, the mechanisms underlying these plastic responses are hitherto not well understood. Therefore, we here investigate effects of adult acclimation on gene expression in the tropical butterfly Bicyclus anynana, using an RNAseq approach. We show that several antioxidant markers (e.g. peroxidase, cytochrome P450) were up-regulated at a higher temperature compared with a lower adult temperature, which might play an important role in the acclamatory responses subsequently providing increased heat tolerance. Furthermore, several metabolic pathways were up-regulated at the higher temperature, likely reflecting increased metabolic rates. In contrast, we found no evidence for a decisive role of the heat shock response. Although the important role of antioxidant defence mechanisms in alleviating detrimental effects of oxidative stress is firmly established, we speculate that its potentially important role in mediating heat tolerance and survival under stress has been underestimated thus far and thus deserves more attention.


Glucose-monitoring neurons in the nucleus accumbens.
The nucleus accumbens, a key structure of the limbic circuitry, is involved in the regulation of motivated behaviors. The accumbens performs its roles via interconnections with brain areas where glucose-monitoring neurons have been localized. To search for such integrative chemosensory cells here, extracellular single neuron activity was recorded in the nucleus accumbens of Wistar rats by means of multibarreled glass microelectrodes during microelectrophoretic administration of D-glucose and other chemicals. Every fourth neuron tested changed in activity in response to glucose. Accumbens cells also displayed distinct gamma-amino-n-butyric acid type sensitivity. It is suggested that differential distribution of the chemosensory units, demonstrated between subdivisions of the nucleus accumbens, has particular significance with respect to functional dichotomy of the shell and core subregions.


[Effect of binocular accommodation and vergence function examinations and interventions on subjective discomfort of dry eye].
Objective: To investigate the accommodation and vergence (AV) function of patients with mild to moderate refractory dry eye symptoms, and determine the impact of relevant interventions on subjective symptoms. Methods: A total of 103 patients with dry eye disease (DED) in Zhongshan Ophthalmic Center between December 2017 and June 2019 were included. After 3-month conventional treatment, the patients entered the treatment-responsive group if ocular surface disease index (OSDI) decreased ≥12.5, and others were recruited into the refractory symptoms group. Binocular AV function, OSDI, tear break-up time (TBUT), Schirmer's test (ST) and fluorescein staining (FL) were determined in all the patients. Corrective therapy on the AV dysfunction was added in the refractory symptoms group besides the conventional therapy. The above-mentioned indexes were reexamined 8 weeks later. The incidence of AV dysfunction was compared between the refractory symptoms group and the treatment-responsive group. Moreover, the differences of OSDI and tear film stability were compared before and after the corrective therapy in the refractory symptoms group. Results: Sixty of 103 DED patients were classified into the refractory symptoms group [mean age: (27±6) years; 18 males and 25 females] and 43 into the treatment-responsive group [mean age: (30±6) years; 32 males and 28 females]. The incidence of AV dysfunction in the refractory symptom group (100%) was higher than that of the treatment responsive group (72.1%) (P<0.001). Forty patients with refractory symptoms accomplished the 8-week corrective therapy, and the OSDI score was significant improved (23.4±16.0 vs 40.6±15.7, P<0.001). However, further changes in ST, TBUT and FL were not detected in these patients (all P>0.05). Conclusions: There is a high prevalence of AV dysfunction in patients with refractory symptomatic DED. The corrective therapy on AV may improve the subjective symptoms in these patients.


Application and Evaluation of a 64-Slice CT Three-Dimensional Fusion Technique in the Determination of the Effective Ablation Margin after Radiofrequency Ablation of Hepatocellular Carcinoma.
Due to the low accuracy of traditional three-dimensional fusion technology in radiofrequency ablation of hepatocellular carcinoma, this paper studies the advantages of three-dimensional CT fusion technology over traditional two-dimensional imaging technology in preoperative visualization and radiofrequency ablation path selection of hepatocellular carcinoma. To study the prognostic differences of hepatocellular carcinoma patients with different ablation margins (AM) in the three groups, so as to explore the best AM value, so as to minimize the liver injury caused by radiofrequency ablation. The selected patients underwent CT plain scan and three-phase enhancement at 1, 3, 6, and 12 months after operation and were rechecked every 6 months. For recurrent patients, CT was rechecked every three months. The images were obtained by GE 64-slice spiral CT. The thickness of the reconstruction layer is 1 mm, and the interval is 1 mm. The reconstructed image is imported into 3D fusion software. The three-dimensional images of tumor focus, hepatic artery, portal vein, and hepatic vein were reconstructed by two experienced doctors by superimposing the saved tumor images, merging the vascular images into the display, and measuring the ablation boundary (AM value). The results showed that the recurrence rate in group A was higher than that in group B (P = 0.041), and there was no significant difference between group B and group C (P = 1.000). Compared with traditional two-dimensional imaging, three-dimensional CT fusion technology can display the anatomical structure and three-dimensional spatial relationship of tumors and blood vessels and select the best radiofrequency ablation path, so as to achieve accurate radiofrequency ablation.