Direct transfer of acute stroke patients to angiography suites equipped with flat-detector computed tomography: literature review and initial single-centre experience.
Background: Time is brain! This paradigm is forcing the development of strategies with potential to shorten the time from symptom onset to recanalization. One of these strategies is to transport select patients with acute ischaemic stroke directly to an angio-suite equipped with flat-detector computed tomography (FD-CT) to exclude intracranial haemorrhage, followed directly by invasive angiography and mechanical thrombectomy if large-vessel occlusion (LVO) is confirmed. Aim: To present existing published data about the direct transfer (DT) of stroke patients to angio-suites and to describe our initial experience with this stroke pathway. Methods: We performed a systematic PubMed search of trials that described DT of stroke patients to angio-suites and summarized the results of these trials. In January 2020, we implemented a new algorithm for acute ischaemic stroke care in our stroke centre. Select patients suitable for DT (National Institute of Health Stroke Scale score ≥10, time from symptom onset to door <4.5 h) were referred by neurologists directly to an angio-suite equipped with FD-CT. Patients treated using this algorithm were analysed and compared with patients treated using the standard protocol including CT and CT angiography in our centre. Results: We identified seven trials comparing the DT protocol with the standard protocol in stroke patients. Among the 628 patients treated using the DT protocol, 104 (16.5%) did not have LVO and did not undergo endovascular treatment (EVT). All the trials demonstrated a significant reduction in door-to-groin time with DT, compared with the standard protocol. This reduction ranged from 22 min (DT protocol: 33 min; standard protocol: 55 min) to 59 min (DT protocol: 22 min; standard protocol: 81 min). In three of five trials comparing the 90-day modified Rankin scale scores between the DT and standard imaging groups, this reduction in ischaemic time translated into better clinical outcomes, whereas the two other trials reported no such difference in scores. Between January 2020 and October 2021, 116 patients underwent EVT for acute ischaemic stroke in our centre. Among these patients, 65 (56%) met the criteria for DT (National Institutes of Health Stroke Scale score >10, symptom onset-to-door time <4.5 h), but only 7 (10.8%) were transported directly to the angio-suite. The reasons that many patients who met the criteria were not transported directly to the angio-suite were lack of personnel trained in FD-CT acquisition outside of working hours, ongoing procedures in the angio-suite, contraindication to the DT protocol due to atypical clinical presentation, and neurologist's decision for obtain complete neurological imaging. All seven patients who were transported directly to the angio-suite had LVOs. The median time from door-to-groin-puncture was significantly lower with the DT protocol compared with the standard protocol {29 min [interquartile range (IQR): 25-31 min] vs. 71 min [IQR: 55-94 min]; P < 0.001}. None of the patients had symptomatic intracranial haemorrhage in the DT protocol group, compared with 7 (6.4%) patients in the standard protocol group. Direct transfer of acute ischaemic stroke patients to the angio-suite equipped with FD-CT seems to reduce the time from patient arrival in the hospital to groin puncture. This reduction in the ischaemic time translates into better clinical outcomes. However, more data are needed to confirm these results.


Fetal death certificates as a source of surveillance data for stillbirths with birth defects.
We assessed fetal death certificates (FDCs) as a source of surveillance for stillbirths with birth defects by linkage with data from the Metropolitan Atlanta Congenital Defects Program (MACDP), a population-based birth defects surveillance system. Stillbirths with defects in MACDP were identified from 1994 through 2002 and linked to FDCs. Sensitivity of FDCs for capturing stillbirths with defects was estimated, and predictors for a case being reported were assessed. Concordance for selected variables from each data source was evaluated. RESILTS: Two hundred twenty-four of 257 stillbirths with birth defects in MACDP were linked to an FDC (linkage rate = 87.2%; 95% confidence interval [CI] 82.4, 91.0). Stillbirths of non-Hispanic black and Hispanic/other mothers were more likely to be issued an FDC (odds ratio [OR] = 5.6 [95% CI 1.9, 17.0] and 14.0 [95% CI 1.7, 114.0], respectively). Cases undergoing autopsy were more likely to be issued an FDC (OR = 3.2; 95% CI 1.1, 8.7). Performance of an amniocentesis was poorly recorded on FDCs. The sensitivity and positive predictive value of FDCs for selected classes of defects ranged from 10% to 70% and 25% to 93%, respectively. Compared to FDCs, MACDP's active case identification improves the ascertainment of stillbirths with birth defects and the quality of certain recorded data.


Immediate results of the use of split-thickness skin autografts with and without acellular dermal matrix in patients with burns, a comparative study in a Colombian population.
Dermal substitutes have become fundamental tools for covering skin defects, most recently with biological subtypes such as glycerolized acellular dermal matrix (GADM). However, literature regarding this matter is scarce in Latin America and Colombia. In this descriptive observational study, we compared the use of partial skin autografts (PSA) combined with GADM and autografts without GADM. Patients were selected from the burn unit of a hospital in northeastern Colombia between 2021 and 2022. Two study groups were defined: one receiving GADM plus PSA, and the other control receiving only a partial split-thickness autograft. A total of 29 patients with 68 body areas were included, with an average age of 20 years. Most cases involved 3rd-degree burns caused by flame. Hospitalization time was the same for both groups (41 days). The percentage of graft take was similar in both groups; in the GADM with autografts group, it was 94.7% compared to 96% in the control group. The presence of complications was similar in both groups. GADM produced in local tissue banks is a cost-effective alternative. It can be used in a single surgical procedure without increasing complications, providing a postsurgical course similar to autografts alone. Granting the potential long-term benefits that dermal matrices give for healing in these patients, which should be evaluated in subsequent studies.


Energetic decomposition with the generalized-born and Poisson-Boltzmann solvent models: lessons from association of G-protein components.
Continuum electrostatic models have been shown to be powerful tools in providing insight into the energetics of biomolecular processes. While the Poisson-Boltzmann (PB) equation provides a theoretically rigorous approach to computing electrostatic free energies of solution in such a model, computational cost makes its use for large ensembles of states impractical. The generalized-Born (GB) approximation provides a much faster alternative, although with a weaker theoretical framework. While much attention has been given to how GB recapitulates PB energetics for the overall stability of a biomolecule or the affinity of a complex, little attention has been given to how the contributions of individual functional groups are captured by the two methods. Accurately capturing these individual electrostatic components is essential both for the development of a mechanistic understanding of biomolecular processes and for the design of variant sequences and structures with desired properties. Here, we present a detailed comparison of the group-wise decomposition of both PB and GB electrostatic free energies of binding, using association of various components of the heterotrimeric-G-protein complex as a model. We find that, while net binding free energies are strongly correlated in the two models, the correlations of individual group contributions are highly variable; in some cases, strong correlation is seen, while in others, there is essentially none. Structurally, the GB model seems to capture the magnitude of direct, short-range electrostatic interactions quite well but performs more poorly with moderate-range "action-at-a-distance" interactions--GB has a tendency to overestimate solvent screening over moderate distances, and to underestimate the costs of desolvating charged groups somewhat removed from the binding interface. Despite this, however, GB does seem to be quite effective as a predictor of those groups that will be computed to be most significant in a PB-based model.


Poly and perfluorinated carboxylates in North American precipitation.
Although perfluorocarboxylates (PFCAs) have been detected in a number of environmental matrices, there are very few reports on concentrations in precipitation. In this study PFCAs, fluorotelomercarboxylates (FTCAs), and fluorotelomer-unsaturated carboxylates (FTUCAs), were determined in wet only precipitation samples from nine sites in North America. The analytical method involved derivatization of the carboxylates and measurement of the 2,4-difluoroanilide by GC-MS. Samples from three remote sites in Canada had low concentrations of perfluorooctanoate (PFOA) (<0.1-6.1 ng/L). Significantly higher concentrations of PFOA were found at 4 northeastern United States and 2 southern urban Canadian sites, with Delaware having the highest levels (85 ng/L PFOA, with a range of 0.6-89 ng/L) and a maximum flux of 13 000 ng/m2. 8:2- and 10:2 FTCAs and FTUCAs were detected at all 4 U.S. sites and 2 urban Canadian sites (<0.07-8.6 ng/L), most frequently at the Delaware site. Longer chained PFCAs (deca-, undeca-, and dodeca-perfluorocarboxylates) were detected (<0.07-5.2 ng/L) at 2 urban Ontario sites but not determined in other samples. Air mass back trajectory results for 3 U.S. sites indicate highly populated urban areas in the New York to Washington corridor as the main sources of PFOA, although low PFOA levels associated with air masses coming off the Atlantic Ocean imply multiple sources.


Weyl's Theory of Glaciation Supported by Isotopic Study of Norwegian Core K 11.
Oxygen-18 analyses of pelagic and benthic foraminifera from core K 11 indicate that during the last glaciation Norwegian Sea bottom waters were warmer than in modern times and had the same physical parameters (temperature, oxygen isotope ratio, and salinity) as the North Atlantic deep water. This result indicates that the glacial Norwegian Sea was not a sink for dense surface water, as it is now, and that during glacial times North Atlantic deep water invaded the deep Norwegian basin.


Multiplex PCR with confronting two-pair primers for CYP1A1 Ile462Val, GSTM1, GSTT1, and NQO1 C609T.
Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an effective genotyping method for single nucleotide polymorphisms (SNPs) in aspects of reducing time and costs for analysis. So far we have established PCR-CTPP conditions for tens of SNPs, including a triplex genotyping (Kawase et al., 2003). In the present study we report a quadruplex PCR-CTPP to genotype simultaneously four functional polymorphisms of carcinogen-metabolizing enzymes, CYP1A1 Ile462Val, GSTM1 null, GSTT1 null and NQO1 C609T, which were reported that they have significant associations with smoking-related cancers. We applied this method for 475 health check-up examinees to demonstrate the performance. Among the subjects, the genotype frequency of CYP1A1 Ile462Val was 56.8% for Ile/Ile, 38.1% for Ile/Val and 5.1% for Val/Val. The null type frequencies of GSTM1 and GSTT1 were 52.8% and 49.9%, respectively. And the genotype frequency of NQO1 C609T was 41.9% for C/C, 41.3% for C/T and 16.8% for T/T. Their distributions were similar to those reported for Japanese by other studies. To the best of our awareness, this is the first paper that reports the success in quadruplex PCR-CTPP. The applied polymorphisms are useful ones, which would be adopted not only for research purposes, but also for risk assessment of individuals exposed to carcinogenic substances. This convenient genotyping would be applied for cancer prevention especially in Asian Pacific regions, where expensive genotyping methods are hardly available.


A new place conditioning paradigm to study tolerance to opiates in mice.
Tolerance to the rewarding properties of morphine was investigated in mice using a new conditioned place preference (CPP) procedure. Four pairings of morphine with specific environmental cues induced a significant CPP for the drug-paired cues. Further opiate conditioning trials in the presence of the same environmental cues revealed no change in the drug-induced CPP on repeated test sessions. Subsequent exposure of the same animals to conditioning trials by pairing morphine with a set of novel environmental cues showed that the opiate was still able to produce a CPP in mice treated with a total of 16 morphine injections. The present CPP paradigm may prove useful to investigate tolerance to the rewarding properties of drugs of abuse.


Context-dependent fluorescence detection of a phosphorylated tyrosine residue by a ribonucleopeptide.
Tools for selective recognition and sensing of specific phosphorylated tyrosine residues on the protein surface are essential for understanding signal transduction cascades in the cell. A stable complex of RNA and peptide, a ribonucleopeptide (RNP), provides effective approaches to tailor RNP receptors and fluorescent RNP sensors for small molecules. In vitro selection of an RNA-derived pool of RNP afforded RNP receptors specific for a phosphotyrosine residue within a defined amino-acid sequence Gly-Tyr-Ser-Arg. The RNP receptor for the specific phosphotyrosine residue was successfully converted to a fluorescent RNP sensor for sequence-specific recognition of a phosphorylated tyrosine by screening a pool of fluorescent phosphotyrosine-binding RNPs generated by a combination of the RNA subunits of phosphotyrosine-binding RNPs and various fluorophore-modified peptide subunits. The phosphotyrosine-binding RNP receptor and fluorescent RNP sensor constructed from the RNP receptor not only discriminated phosphotyrosine against tyrosine, phosphoserine, or phosphothreonine, but also showed specific recognition of amino acid residues surrounding the phosphotyrosine residue. A fluorescent RNP sensor for one of the tyrosine phosphorylation sites of p100 coactivator showed a binding affinity to the target site ~95-fold higher than the other tyrosine phosphorylation site. The fluorescent RNP sensor has an ability to function as a specific fluorescent sensor for the phosphorylated tyrosine residue within a defined amino-acid sequence in HeLa cell extracts.


At-risk drinking among patients in an occupational medicine clinic.
This study described the prevalence and characteristics of at-risk drinkers among adults receiving care at an urban occupational medicine clinic. Comparisons were also made between occupational medicine and primary care patients. Among occupational medicine patients, prevalences were: 11% at-risk drinking; 51% light-moderate drinking; 38% abstinence. Abstainers differed from alcohol users with regard to race (fewer Caucasian) and marijuana use (lower rates). Compared to light-moderate drinkers, at-risk drinkers were more likely to be smokers. Compared to a primary care sample, non-at-risk drinkers in occupational medicine reported poorer health, more activity limitations, higher rates of smoking and more stress and depressive symptoms. In contrast, at-risk drinkers in occupational medicine were quite similar to those in primary care. Occupational medicine clinics are viable settings in which to screen for at-risk drinking patterns and to implement primary and secondary prevention strategies.


Molecular dynamics simulations reveal how H3K56 acetylation impacts nucleosome structure to promote DNA exposure for lesion sensing.
The first order of DNA packaging is the nucleosome with the DNA wrapped around the histone octamer. This leaves the nucleosomal DNA with access restrictions, which impose a significant barrier to repair of damaged DNA. The efficiency of DNA repair has been related to nucleosome structure and chromatin status, which is modulated in part by post-translational modifications (PTMs) of histones. Numerous studies have suggested a role for acetylation of lysine at position 56 of the H3 histone (H3K56ac) in various DNA transactions, including the response to DNA damage and its association with human cancer. Biophysical studies have revealed that H3K56ac increases DNA accessibility by facilitating spontaneous and transient unwrapping motions of the DNA ends. However, how this acetylation mark modulates nucleosome structure and dynamics to promote accessibility to the damaged DNA for repair factors and other proteins is still poorly understood. Here, we utilize approximately 5-6 microseconds of atomistic molecular dynamics simulations to delineate the impact of H3K56 acetylation on the nucleosome structure and dynamics, and to elucidate how these nucleosome properties are further impacted when a bulky benzo[a]pyrene-derived DNA lesion is placed near the acetylation site. Our findings reveal that H3K56ac alone induces considerable disturbance to the histone-DNA/histone-histone interactions, and amplifies the distortions imposed by the presence of the lesion. Our work highlights the important role of H3K56 acetylation in response to DNA damage and depicts how access to DNA lesions by the repair machinery can be facilitated within the nucleosome via a key acetylation event.


The value of ultrasound-guided fine needle aspiration in the assessment of solid breast lumps.
To assess the value of routine ultrasound-guided fine needle aspiration (US-FNA) of solid mass lesions of the breast, all such patients presenting to the breast clinic over a 5 month period were offered US-FNA in addition to standard imaging. One thousand, three hundred and eight-six consecutive patients were assessed and 77 solid mass lesions identified. US-FNA was performed in 49 of these. Sixteen demonstrated cytological features of malignancy that was confirmed at surgery. US-FNA did not diagnose malignancy in cases with typical benign imaging features. It did alter diagnosis from an equivocal suspicious mass lesion to a definite diagnosis of malignancy in four cases (25%). It also altered diagnosis from an equivocal, probably benign, diagnosis to a more confident diagnosis of benign disease in 18 (58%) of benign cases. US-FNA confirmed the diagnosis of malignancy in four cases where a suspicious mass could only be imaged by ultrasound. US-FNA is simple, rapid and, unlike large Tru-Cut biopsies, is not associated with complications. It causes only minimal discomfort to both patient and operator. We recommend that US-FNA becomes a routine component of the imaging workup of breast mass lesions both to exclude malignancy in equivocal cases and to confirm malignancy when this is expected.


Transition-Metal-Free Carbon Isotope Exchange of Phenyl Acetic Acids.
A transition-metal-free carbon isotope exchange procedure on phenyl acetic acids is described. Utilizing the universal precursor CO2 , this protocol allows the carbon isotope to be inserted into the carboxylic acid position, with no need of precursor synthesis. This procedure enabled the labeling of 15 pharmaceuticals and was compatible with carbon isotopes [14 C] and [13 C]. A proof of concept with [11 C] was also obtained with low molar activity valuable for distribution studies.


Brain mediation of Anolis social dominance displays. I. Differential basal ganglia activation.
Ritualistic displays of aggressive intent are important social signals, often obviating physically dangerous engagement. To date, however, brain regions mediating such behaviors are not established. Here we used male Anolis carolinensis together with an in vivo 14C-2-deoxyglucose method to determine patterns of brain activation during elicitation of this animal's dominance displays vs. other behaviors. By patching one eye regional brain activation in the hemisphere receiving display-evocative visual stimuli ('seeing' side) was compared to activity in the contralateral brain that did not see specific stimuli ('patched' side); this was quantitated as the ratio of seeing/patched activity for brain regions of interest. Lone males displaying dominantly to mirrors activated dorsolateral basal ganglia (BG) in the seeing, compared to the patched hemisphere; this was not seen in various non-displaying controls. Degree of dorsolateral BG activation also correlated with a measure of dominant display activity, but not with locomotion. In socially stable pairs, displaying dominants showed similar activation of dorsolateral BG, but deactivated ventromedial BG; non-dominant cagemates displaying submissively had the opposite pattern. When cohabiting peacefully without displaying, paired dominants' and subordinates' brain activity patterns were similar to each other. Thus, different BG subsystems seem involved in dominant vs. submissive display behaviors. Given similarities in both social displays and BG organization, homologous brain systems might have similar functions in members of other amniote classes, including primates.


A comparative study of the activity of a new agent, indapamide, in essential arterial hypertension.
A single-blind crossover trial was carried out in 38 elderly, hospitalised patients with essential hypertension to compare the hypotensive activity of 5 mg. indapamide daily with 100 mg. chlorthalidone daily. After initial treatment for 10 days with placebo, patients received treatment for 45 days with either indapamide or chlorthalidone and were then crossed over to the alternative drug for a similar period. Potassium supplementation was necessary in 25 of the patients receiving chlorthalidone, but was precribed as a precautionary measure in only 1 patients whilst on indapamide. Results showed that there were significant drops in blood pressure following both active medications, but that the percentage reduction in diastolic pressure was greater after indapamide. Indapamide also proved more effective than chlorthalidone in controlling the patients' subjective and functional symptoms of their hypertension. In an overall assessment of the effectiveness of both drugs, indapamide was judged to be better tolerated as well as more effective than chlorthalidone in 18 of the 38 patients, whilst chlorthalidone was preferred in only 7 instances.


100K Pathogen Genome Project.
The 100K Pathogen Genome Project is producing draft and closed genome sequences from diverse pathogens. This project expanded globally to include a snapshot of global bacterial genome diversity. The genomes form a sequence database that has a variety of uses from systematics to public health.


Identification of high-risk individuals for hip fracture: a 14-year prospective study.
In this 14-year prospective study, men and women were found to share a common set of risk factors for hip fracture: low BMD, postural instability and/or quadriceps weakness, a history of falls, and prior fracture. The combination of these risk factors accounted for 57% and 37% of hip fractures in women and men, respectively. Risk factors for hip fracture, including low BMD, identified in women, have not been shown to be useful in men. It is also not known whether fall-related factors (muscle strength and postural instability) predict hip fracture. This study examined the association between falls-related factors and hip fractures in elderly men and women. This is an epidemiologic, community-based prospective study, which included 960 women and 689 men > or = 60 years of age who have been followed for a median of 12 years (interquartile range, 6-13). The number of person-years was 9961 for women and 4463 for men. The outcome measure was incidence of hip fracture. Risk factors were femoral neck BMD (FNBMD), postural sway, quadriceps strength, prior fracture, and fall. Between 1989 and 2003, 115 (86 women) sustained a hip fracture. The risk of hip fracture (as measured by hazards ratio [HR]) was increased by 3.6-fold (95% CI: 2.6-4.5) in women and 3.4-fold (95% CI: 2.5-4.6) in men for each SD (0.12 g/cm2) reduction in FNBMD. After adjusting for BMD, the risk of hip fracture was also increased in individuals with the highest tertile of postural sway (HR: 2.7; 95% CI: 1.6-4.5) and low tertiles of quadriceps strength (HR: 3.0; 95% CI: 1.3-6.8). Furthermore, a history of fall during the preceding 12 months and a history of fracture were independent predictors of hip fracture. For each level of BMD, the risk of hip fracture increased linearly with the number of non-BMD risk factors. Approximately 57% and 37% of hip fracture cases in women and men, respectively, were attributable to the presence of risk factors, osteoporosis (BMD T score < or = -2.5), and advancing age. Men and women had a common set of risk factors for hip fracture: low BMD, postural instability and/or quadriceps weakness, a history of falls, and prior fracture. Preventive strategies should simultaneously target reducing falls and improvement of bone strength in both men and women.


[Remitted anxiety states: a specific variant of generalized anxiety disorder].
Two hundreds and four patients with generalized anxiety disorder (GAD) have been divided into 2 groups: 107 patients with remitted course (a main group) and 97 patients with the typical development of GAD (a comparison group). It has been shown that the main group is characterized by the lower intensity of anxiety affect and reactivity and the lesser duration of exacerbations. The remissions, when the tension of anxiety is completely absent or has a subclinical character, last from 2-3 weeks to 2-3 months. In the treatment, patients with remitted disorders prefer psychotherapy (44,9%) or combined therapy (psychotherapy and pharmacotherapy) - 38,85% of cases. Despite of some peculiarities remitted anxiety disorders should be considered as a variant of GAD thus confirming their unity.


Human eosinophils express functional CCR7.
Human eosinophils display directed chemotactic activity toward an array of soluble chemokines. Eosinophils have been observed to migrate to draining lymph nodes in experimental models of allergic inflammation, yet it is unknown whether eosinophils express CCR7, a key chemokine receptor in coordinating leukocyte trafficking to lymph nodes. The purpose of this study is to demonstrate expression of CCR7 by human eosinophils and functional responses to CCL19 and CCL21, the known ligands of CCR7. Human eosinophils were purified by negative selection from healthy donors. CCR7 expression of freshly purified, unstimulated eosinophils and of IL-5-primed eosinophils was determined by flow cytometry and Western blot. Chemotaxis to CCL19 and CCL21 was measured in transwell assays. Shape changes to CCL19 and CCL21 were analyzed by flow cytometry and microscopy. Calcium fluxes of fluo-4 AM-loaded eosinophils were recorded by flow cytometry after chemokine stimulation. ERK phosphorylation of CCL19- and CCL21-stimulated eosinophils was measured by Western blot and Luminex assay. Human eosinophils expressed CCR7 as demonstrated by flow cytometry and Western blots. Eosinophils exhibited detectable cell surface expression of CCR7. IL-5-primed eosinophils exhibited chemotaxis toward CCL19 and CCL21 in a dose-dependent fashion. Upon stimulation with CCL19 or CCL21, IL-5-primed eosinophils demonstrated dose-dependent shape changes with polarization of F-actin and exhibited calcium influxes. Finally, primed eosinophils stimulated with CCL19 or CCL21 exhibited increased phosphorylation of ERK in response to both CCR7 ligands. We demonstrate that human eosinophils express CCR7 and have multipotent responses to the known ligands of CCR7.


Single-Dose, Patient-Initiated Amenamevir Therapy for Recurrent Genital Herpes: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study.
Amenamevir is a helicase-primase inhibitor with novel mechanisms of antiherpetic action. A patient-initiated single-dose regimen showed clinical efficacy for genital herpes in a phase 2 study. In this phase 3 study, adult immunocompetent patients with recurrent genital herpes and able to accurately recognize prodromal symptoms were randomly assigned to administer amenamevir 1200 mg or placebo as a patient-initiated therapy within 6 hours after onset of prodromal symptoms. The primary efficacy endpoint was time to healing of all genital herpes lesions. In the modified intention-to-treat population, which excluded patients with aborted lesions (amenamevir, n = 89; placebo, n = 97), the median time to all lesion healing was 4.0 days for amenamevir versus 5.1 days for placebo (hazard ratio, 1.60 [95% confidence interval, 1.19-2.15]; P = .0018), indicating superiority of amenamevir. All treatment-emergent adverse events in both groups were mild in severity. Patient-initiated single-dose amenamevir reduced the time to all lesion healing of recurrent genital herpes versus placebo, with no safety concerns, suggesting it could be an effective treatment option for patients with recurrent genital herpes. Clinical Trials Registration. JapicCTI-194955.


Pigeons' choices with token stimuli in concurrent variable-interval schedules.
Twelve pigeons responded on concurrent variable-interval schedules that delivered token stimuli (stimulus lights for some pigeons, and white circles on the response keys for others). During exchange periods, each token could be exchanged for food on a fixed-ratio 1 schedule. Across conditions, the exchange requirements (number of tokens that had to be earned before they could be exchanged for food) varied between one and four for the two response keys. The main findings were that the pigeons' response percentages varied as a function of the number of tokens earned at any given moment, and they were determined by both the delays to food and by the number of food deliveries in the exchange periods. In some conditions, tokens had to be earned but were not visible during the variable-interval schedules for one or both keys. When one key had visible tokens and the other did not, the pigeons showed a preference for the key without visible tokens. A model based on the matching law and a hyperbolic delay-discounting equation could account for the main patterns of choice responding, and for how response percentages changed as successive tokens were earned. The results are consistent with the view that the token stimuli served as discriminative stimuli that signaled the current delays to food.


Interaction of phentermine plus fenfluramine: neurochemical and neurotoxic effects.
Previous studies have reported the use of combined serotonergic and dopaminergic agonists in the treatment of obesity and alcoholism. Along these lines, phentermine plus fenfluramine has been suggested as a possible clinical treatment for alcohol craving. To determine the neurochemical effects of a combined treatment of phentermine plus fenfluramine, animals were injected subcutaneously with saline, phentermine 12 mg/kg, fenfluramine 16 mg/kg, or a combination of phentermine plus fenfluramine. One hour after injection, animals were sacrificed and neurochemical analysis performed. Furthermore, separate groups of animals were given the same injections 8 times, 12 hours apart, to determine the effects on body weight and to detect a possible exacerbation of fenfluramine induced toxicity. The drug combination produced a significant rise in dopamine in the striatum, greater than that seen with either drug alone. Furthermore, the addition of phentermine reduced the fenfluramine induced rise in striatal 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindolacetic acid (5-HIAA). Phentermine plus fenfluramine combination produced a greater weight loss than either drug alone, however, it did not produce a significantly greater drop in striatal serotonin or 5-HIAA levels above that induced by fenfluramine alone. Thus, while previous studies report the potentiated neurotoxicity of phentermine plus fenfluramine over fenfluramine alone, the present study does not indicate that such an effect occurs following an administration regimen analogous to that of patients treated with the drug combination.


A hospital-based study on the use of paramedical personnel for clinical downstaging of cancer cervix.
Two auxiliary nurse midwives (ANMs) were recruited and trained to recognize normal and different types of abnormal cervices. A total of 2102 women were examined by a gynaecologist and ANM independently and their findings were noted. Comparison of their findings showed an overall agreement of 89.6 per cent (Kappa 0.84 with standard error of 0.015 and a significantly large Z value of 55.6). Gross examination of 4679 women attending the Gynaecology OPD revealed normal cervix in 49.6 per cent and suspected lesions or malignant cervix in 3.4 per cent of women. Cytology smears were taken in 3608 women. Adequacy of smears was 97 per cent. Comparing the group clinically diagnosed as highly suspected or malignant to the cytologically diagnosed suspected group (atypical and malignant), clinical examination had a sensitivity of 81.7 per cent and specificity of 97.3 per cent; while comparison of the group clinically diagnosed as abnormal cervix to abnormal cytology (all grades of dysplasia, atypical and malignant cells), the clinical examination had a sensitivity of 92.5 per cent and specificity of 37.4 per cent. It was concluded that paramedical staff (ANMs) can be relied upon to do speculum examination in women in the community and take cytology smears in selected cases.


Subunit composition of lipoprotein(a) protein.
We determined the molecular weight of four different apo(a) polymorphs by sedimentation equilibrium in 6 M guanidine hydrochloride in order to estimate the molar ratio of apo(a) to apoB in Lp(a). They had molecular weights of 289,000, 310,000, 341,000, and 488,000 and 15, 16, 18, and 27 kringle 4 domains, respectively. Their carbohydrate content was similar (23.2 wt %), as was their partial specific volume (0.682 mL/g). Knowing the mass of apo(a), we estimated the molar ratio of apo(a) to apoB from (1) the molecular weight of the protein moiety of the four respective parent Lp(a) particles as calculated from their mass and percentage composition and the mass of apoB, (2) the mass of apo(a) lost from Lp(a) upon its reduction and carboxymethylation, by determining the difference in mass between Lp(a) and Lp(a-), and (3) from the mass (measured by sedimentation equilibrium in 6 M guanidine hydrochloride) of the lipid-free apoB-apo(a) complex (1.06 x 10(6) daltons) of the Lp(a) particle with the smallest apo(a) polymorph by subtracting the mass of apoB. Our results obtained with each of the three different physicochemical methods indicated that the protein moiety of each of the four Lp(a) particles that was investigated consisted of a complex of two molecules of apo(a) and one molecule of apoB.


Uncovering and responding to needs for sexual and reproductive health care among poor urban female adolescents in Nicaragua.
To meet the needs of female adolescents from low-income urban areas for sexual and reproductive health (SRH) care, vouchers providing free-of-charge access to SRH care at 19 primary care clinics were distributed in Managua, Nicaragua. These vouchers substantially increased the use of services, demonstrating that many adolescents are willing to use such services, if readily accessible. The voucher redemption made it possible to identify the nature of existing, but largely unmet, needs for SRH care. The medical files from 3301 consultations with female adolescents were analysed using descriptive statistical methods and multiple logistic regression. Female adolescents presented SRH problems that merited medical attention. The mean number of problems presented was 1.5 per consultation: 34% of the vouchers were used for contraceptives, 31% for complaints related to sexually transmitted infection (STI) or reproductive tract infection (RTI), 28% for advice/counselling, 28% for antenatal check-up and 18% for pregnancy testing. A new category of health care users emerged: sexually active girls who were neither pregnant nor mothers and who sought contraceptives or STI/RTI treatment. Contraceptive use doubled among the sexually active non-pregnant voucher redeemers. Consultation with a female doctor younger than 36 years was associated with a higher chance of having contraceptives prescribed. Accessible and appropriate SRH care has the potential to make an important contribution to the increased contraceptive use, decreased risk of unwanted teenage pregnancies and decreased prevalence of STIs/RTIs among underserved adolescents. Once adolescents access the services, providers have a crucial role in ensuring current and continuing needs are met.


Genetic polymorphisms in GSTA1, GSTP1, GSTT1, and GSTM1 and gastric cancer risk in a Vietnamese population.
Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of noxious agents. Genes encoding for GSTA1, GSTP1, GSTT1, and GSTM1 proteins are polymorphic in humans, which can result in (partial) loss of enzyme activity. Previous epidemiologic studies have associated dysfunction of these GST genes with a higher risk of cancer, but this is still controversial. The aim of this study was to investigate the susceptibility to gastric cancer in relation to the above-mentioned GST polymorphisms. Patients visiting the Can Tho General Hospital in Vietnam between January 2004 and August 2004 for upper gastrointestinal endoscopy, who were diagnosed with gastric cancer, were compared with a control group of endoscoped dyspepsia patients with no history of malignancy. Genotypes of the GSTs mentioned above were assessed by multiplex PCR. Fifty-nine patients with gastric cancer (mean age: 63 years, 80% males), and 109 dyspeptic controls (mean age: 46 years, 69% males) were included in this study. The frequencies of the combined heterozygote and homozygote mutant GSTA1 and GSTP1 genotypes were 10% and 48% in patients with gastric cancer versus 28% and 40% in dyspeptic controls, respectively. GSTT1 and GSTM1 were deleted in 42% and 73% of patients with gastric cancer and in 35% and 69% of the controls, respectively. The GSTA1 homozygous wild-type genotype was significantly more often present in patients with gastric cancer compared with controls (odds ratio 4.3, 95% CI 1.2-17), which was even more apparent after adjustment for age, gender, current smoking, current alcohol consumption, and polymorphisms in GSTP1, GSTT1, or GSTM1 (odds ratio 5.0, 95% CI 1.2-25). The present work shows that the homozygous wild-type GSTA1 genotype is associated with gastric cancer in a Vietnamese population, whereas there was no relationship with polymorphisms in GSTP1, GSTT1, or GSTM1.


Five-year Safety Data for Eurosilicone's Round and Anatomical Silicone Gel Breast Implants.
Multicenter prospective studies assessing the safety and efficacy of silicone gel breast implants are relatively rare. Eurosilicone S.A.S. present their safety and efficacy data herein for the largest European silicone gel breast implant study published to date. One thousand and ten of Eurosilicone's textured cohesive Cristalline Paragel range of mammary implants was implanted in women undergoing augmentation and reconstructive surgery at 17 centers throughout France. Physical examinations and complications were recorded by physicians at 3 months and annually thereafter until 10 years postimplantation. Descriptive statistics were used and key complications were analyzed using the Kaplan-Meier analysis method. Two ruptures were observed within 5 years postimplantation, one of which was subject to mechanical trauma during reoperation and the other was identified during routine screening. Capsular contracture, one of the most common complications associated with breast implants, was reported in 6.6% implants across all indications through 5 years. The Kaplan-Meier risk of capsular contracture (Baker III/IV) was 10.7% (95% confidence interval, 7.2-14.2%) and 17.2% (95% confidence interval, 5.4-29%) in the primary augmentation and primary reconstruction patient cohorts, respectively. Implant removal (explantation/exchange) was 8.5% and 16.5% for primary augmentation and primary reconstruction cohorts, respectively. Rates of local complications including infection and seroma were low with risk rates of 0.6% and 0.2% by subject. Eurosilicone S.A.S. prospective study involving 1010 Eurosilicone silicone gel breast implants in both round and shaped profiles demonstrated a low rupture rate and an excellent safety profile through 5 years.


Effect of environmental variables and their interaction on gordiid hairworm larvae (Nematomorpha).
The different stages of the life cycle of parasites are important components of ecosystems. Changes in environmental conditions may affect free-living stages, host-parasite interactions and ecosystem functioning. The larvae of Chordodes nobilii, which belongs to the parasitic phylum Nematomorpha, are susceptible to extreme temperatures and different pollutants, but the effects of pH and moderate temperature variations have not been evaluated yet. Our objective was to assess the effect of temperature, pH and their interaction on the infectivity of C. nobilii larvae to Aedes aegypti larvae over time. Larvae were treated with factorial combinations of temperature (18, 23 and 28°C), pH (7, 8 and 9) and time periods (24 and 48 h). Results show a highly significant interaction among all variables. The highest infectivity was recorded at 18°C and pH 7 at 24 and 48 h, and the lowest one at 28°C and pH 8 at 24 and 48 h. Infectivity differed significantly among the three temperatures only at pH 8 and 48 h, decreasing with increasing temperature. Our study is the first report of the effect of pH on a Nematomorpha species and suggests that the infectivity of C. nobilii larvae may be affected negatively by an increase in temperature and its interaction with pH and time. Since parasites must be considered for a better understanding of the effects of stressors on freshwater ecosystems, our results may help in the design and analysis of studies of anthropogenic impact.


Engineering skyrmions in transition-metal multilayers for spintronics.
Magnetic skyrmions are localized, topologically protected spin structures that have been proposed for storing or processing information due to their intriguing dynamical and transport properties. Important in terms of applications is the recent discovery of interface stabilized skyrmions as evidenced in ultra-thin transition-metal films. However, so far only skyrmions at interfaces with a single atomic layer of a magnetic material were reported, which greatly limits their potential for application in devices. Here we predict the emergence of skyrmions in [4d/Fe2/5d]n multilayers, that is, structures composed of Fe biatomic layers sandwiched between 4d and 5d transition-metal layers. In these composite structures, the exchange and the Dzyaloshinskii-Moriya interactions that control skyrmion formation can be tuned separately by the two interfaces. This allows engineering skyrmions as shown based on density functional theory and spin dynamics simulations.


Clinical outcome of patients examined by capsule endoscopy for suspected small bowel Crohn's disease.
Capsule endoscopy has a greater diagnostic yield than radiology for detecting subtle inflammatory changes of the small bowel mucosa, but the clinical significance of these abnormalities is still uncertain because of the lack of long-term follow-ups. To verify the accuracy of capsule endoscopy in a cohort of patients with suspected Crohn's disease of the small bowel, taking as 'gold standard' the final diagnosis made after a long follow-up. From April 2002 to March 2005, we enrolled and examined by capsule endoscopy 27 consecutive patients with abdominal pain and diarrhea lasting more than 3 months and at least one of the following: anaemia, weight loss, fever, extra-intestinal manifestation(s) of inflammatory bowel disease. All patients already had an unremarkable pan-endoscopy, serology for celiac disease and intestinal radiology inconclusive for small bowel abnormality. On the basis of capsule endoscopy findings, patients were distributed in three groups; Group A had severe stricturing lesions requiring surgery; Group B, moderate inflammatory lesions further investigated invasively; Group C, minimal inflammatory changes or normal findings, clinically observed every 3 months (median 21 months, range 15-29). Small bowel inflammatory lesions were found in 16 of the 27 patients (diagnostic yield 59%). Three had surgery (Group A) and Crohn's disease was confirmed in two; the remainder had ileal adenocarcinoma in a pathological context of chronic inflammation. Crohn's disease was histologically confirmed in four of the five patients in Group B. Group C comprised 19 patients; Crohn's disease was confirmed in seven out of eight with positive capsule endoscopy, while only one of the patients with normal findings later developed overt ileal Crohn's disease. Sensitivity, specificity, positive and negative likelihood ratio were, respectively, 93%, 84%, 5.8 and 0.08. Assuming a 50% pre-test probability of disease, capsule endoscopy gave a post-test probability of 85%. In our selected cohort, capsule endoscopy was highly sensitive in detecting small bowel inflammatory changes, enhancing by nearly 35% the pre-test probability of structural small bowel disease. Focal erythema and luminal debris may limit the specificity of capsule endoscopy.


Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives.
Bone biomarkers included formation, resorption and regulator are released during the bone remodeling processes. These bone biomarkers have attracted much attention in the clinical assessment of osteoporosis treatment in the past decade. Combination with the measurement of bone mineral density, the clinical applications of bone biomarkers have provided comprehensive information for diagnosis of osteoporosis. However, the analytical approaches of the bone biomarkers are still the challenge for further clinical trials. In this mini-review, we have introduced the functions of bone biomarkers and then recently developed techniques for bone biomarker measurements have been systematically integrated to discuss the possibility for osteoporosis assessment in the early stage.


Demonstration of antigenic heterogeneity of Neisseria gonorrhoeae pili antigens using human sera in the test system.
Antigenic heterogeneity of gonococcal pili using human sera in the test system was demonstrated by means of indirect haemagglutination (IHA) inhibition studies. The reactivities of sera from 104 females with current gonococcal infection were compared by the IHA test using different pili preparations as antigens. Sera and gonococcal strains were collected from 365 patients. Pili were purified from strains infecting patients who met the following three requirements: 1) no history of previous gonococcal infection(s), 2) an infection that had lasted a week or more, 3) a seronegative result when tested by the IHA test using pili from Buchanan's strain 2686 as antigen. Each patient's serum was tested against pili produced by the gonococcal strain infecting this particular patient. A seropositive reaction obtained by using pili antigen from the strain infecting the seronegative (strain 2686) patient indicates an antigenically heterogeneous pili preparation. Two such strains, antigenically different from one another and from strain 2686, were found among 22 pili preparations investigated.


Digital image technology based on PCA and SVM for detection and recognition of foreign bodies in lyophilized powder.
Digital image technology has made great progress in the field of foreign body detection and classification, which is of great help to drug purity extraction and impurity analysis and classification. The detection and classification of foreign bodies in lyophilized powder are important. The method which can obtain a higher accuracy of recognition needs to be proposed. We used digital image technology to detect and classify foreign bodies in lyophilized powder, and studied the process of image preprocessing, median filtering, Wiener filtering and average filtering balance to better detect and classify foreign bodies in lyophilized powder. Through industrial small sample data simulation, test results show that in the process of image preprocessing, 3 × 3 median filtering is best. In the aspect of foreign body recognition, the recognition based on principal component analysis (PCA) and support vector machine (SVM) algorithm and the recognition based on PCA and Third-Nearest Neighbor classification algorithm are compared and results show that the PCA+SVM algorithm is better. We demonstrated that integrating PCA and SVM to classify foreign bodies in lyophilized powder. Our proposed method is effective for the prediction of essential proteins.


IgM nephropathy in adults: incidence and correlation with electron microscopic features.
IgM nephropathy is characterised on light microscopy (LM) by variable features of normal glomeruli to mesangial hypercellularity; and immunofluorescence (IF) deposits of LgM. Our aim was to study the incidence of IgM nephropathy in adults with primary glomerular disease, with correlation to electron microscopy (EM) features. All adults presenting with proteinuria glomerular hematuria underwent renal biopsy. We excluded patients with systemic diseases and post-infectious glomerulonephritis. All the specimens were evaluated by LM, IF and EM. Our series had 146 cases. Of the 42 cases diagnosed on LM as minimal change disease, mesangial deposition of IgM was present in 11 cases. In addition there were seven cases of mesangioproliferative glomerulonephritis with mesangial IgM deposition. Thus, there were a total of 18 cases of IgM nephropathy (12.3%). Only six of these 18 cases showed typical electron dense deposits in the mesangium on EM. We feel that IgM nephropathy is probably a separate pathological entity, comprising 12.3% of all adults with primary chronic glomerulopathy. Electron dense deposits are seen in only about a third of these cases.


Severity of hip dysplasia as the major factor affecting outcome of closed reduction in children with hip dysplasia.
The objective of this study was to analyze a multicenter cohort of children with developmental dysplasia of the hip (DDH) who underwent treatment with closed reduction. We sought to report the effects that severity of hip dysplasia and age have on the development of femoral head avascular necrosis (AVN) and the need for additional procedures. All patients with DDH and minimum 2 years of follow-up who underwent closed reduction were identified. The following variables were recorded: sex, laterality of hip involvement, age, acetabular index (AI), and International Hip Dysplasia Institute (IHDI) grade. The effects of patient age and pre-procedure IHDI grade on the rate of AVN and need for additional procedures after the closed reduction were analyzed using an alpha of 0.05. Seventy-eight total hips were included in the final analysis. The average patient age was 12 months. AVN of the femoral head was reported in 24 hips (30.8%) and 32 hips (41.0%) required additional surgery. Higher pre-op IHDI grade was associated with higher risk of developing Bucholz-Ogden grades II-IV AVN of the femoral head (P = 0.025) and requiring additional surgery (P= 0.033) regardless of patient age. There were no statistically significant differences for the effect of age on the measured outcomes (P > 0.05). These findings suggest that severity of dislocation (IHDI grade) is a significant risk factor for the development of AVN and need for additional procedure.


Comparison of moments and couple-generating forces near discontinuities in structural-acoustic systems.
In modeling vibration isolators in structural-acoustic systems, the isolator's dynamic properties are often treated as acting only in the axial direction as moments are often neglected. Furthermore, the size, or scale, of the isolator is often neglected and the isolator is assumed to act at single points on the connected structures. Previous work has shown that concentrated moments can be particularly important when located near a fixed support or a structural discontinuity. This research extends that work to examine the importance of moment scale effects for a system containing a distributed structural discontinuity with its own scale. Moment scale effects are examined by determining the difference in radiated acoustic power for a simple system that is excited by a couple-generating distributed force and a concentrated moment. The distributed force produces a couple that is equivalent to the concentrated moment. As a result, only the scale is being examined. Particular interest occurs when the excitation is located near the structural discontinuity. Based on the cases studied here, moment scale is shown to be important at lower frequencies when the excitation is located near the edges of the discontinuity. At higher frequencies, any overlap of the excitation and discontinuity may warrant the need to consider moment scales.


Monocyclometalated (C N) Gold(III) Metallacycles: Tunable Emission and Singlet Oxygen (1 O2 ) Generation Properties.
The synthesis, characterization and photoluminescent properties of four cyclometalated (C N)-type gold(III) complexes bearing a bidentate diacetylide ligand, tolan-2,2'-diacetylide (tda), are reported. The complexes exhibit highly tunable excited state properties and show photoluminescence (PL) across the entire visible spectrum from sky-blue (λPL =493 nm) to red (λPL =675 nm) with absolute PL quantum yields (PLQY) of up to 75 % in solution, the highest PLQY found for any monocyclometalated Au(III) complex in solution. As a consequence of the use of the strongly rigidifying diacetylide bidentate ligand, a significant increase in the excited state lifetimes (τ0 =16-258 μs) was found in solution and in thin films. The complexes showed remarkable singlet oxygen generation in aerated solution with absolute singlet oxygen quantum yield (ϕ1Δ ) values reaching up to 7.5×10-5 and singlet oxygen lifetimes (τ0 1Δ ) in the range of 66-95 μs. Furthermore, the radiative and non-radiative rates of singlet oxygen were determined using the ϕ1Δ and τ0 1Δ values and correlations are drawn between the formation of singlet oxygen and its interaction with cyclometalated (C N) gold(III) complexes.


Effects of packaging and heat transfer kinetics on drug-product stability during storage under uncontrolled temperature conditions.
To predict the stability of pharmaceutical preparations under uncontrolled temperature conditions accurately, a method to compute the average reaction rate constant taking into account the heat transfer from the atmosphere to the product was developed. The average reaction rate constants computed with taken into consideration heat transfer (κ(re) ) were then compared with those computed without taking heat transfer into consideration (κ(in) ). The apparent thermal diffusivity (κ(a) ) exerted some influence on the average reaction rate constant ratio (R, R = κ(re) /κ(in) ). In the regions where the κ(a) was large (above 1 h(-1) ) or very small, the value of R was close to 1. On the contrary, in the middle region (0.001-1 h(-1) ), the value of R was less than 1.The κ(a) of the central part of a large-size container and that of the central part of a paper case of 10 bottles of liquid medicine (100 mL) fell within this middle region. On the basis of the above-mentioned considerations, heat transfer may need to be taken into consideration to enable a more accurate prediction of the stability of actual pharmaceutical preparations under nonisothermal atmospheres.


Rasburicase for huge hepatocellular carcinoma with tumor lysis syndrome: case report.
To report a case of huge hepatocellular carcinoma associated with tumor lysis syndrome and its management. A 51-year-old hepatitis B carrier visited our clinic with progressive weight loss over recent months. Abdominal ultrasonography and magnetic resonance imaging revealed a huge hepatic mass in a cirrhotic liver, identified as hepatocellular carcinoma. A hepatologist and surgeon recommended transarterial chemoembolization followed by hepatectomy. The patient underwent the procedure, with the complication of tumor lysis syndrome. He was treated with a single high dose (9 mg) of rasburicase and his clinical condition improved dramatically, with acute kidney injury subsiding without emergent hemodialysis. This was a case of hepatocellular carcinoma with tumor lysis syndrome and acute kidney injury, treated successfully with rasburicase.


[Scratching for the itch in eczema; a psychodermatologic approach].
Atopic dermatitis patients often complain of intense itching and excessive scratching. Apart from standard therapies of antihistamines with sedative side effects, there are patients who appear not to respond satisfactorily to standard medical treatments. As itching can be a skin manifestation of psychological disturbance, these patients may benefit from behaviour treatment of scratch behaviour which can have a beneficial effect on the course of atopic eczema. The scratch response is considered a classical conditioned habit and special attention was given to the function of behaviour. Two patients, a man of 27 and a girl of 11, were suffering from intractable atopic eczema. The first patient was required to record his own scratching in a diary which is part of awareness training regarding scratch situations. In the second patient impaired parent-child relationships were the main discriminative stimuli to provoke scratch behaviour. It was shown that behaviour therapy helps patients who scratch repeatedly to exercise voluntary control over it.


The 55-kDa tumor necrosis factor receptor induces clustering of mitochondria through its membrane-proximal region.
The cytokine tumor necrosis factor (TNF) activates diverse signaling molecules resulting in gene expression, differentiation, and/or cell death. Here we report a novel feature induced by TNF, namely translocation of mitochondria from a dispersed distribution to a perinuclear cluster. Mitochondrial translocation correlated with sensitivity to the cell death-inducing activity of TNF and was mediated by the 55-kDa TNF receptor (TNF-R55), but not by Fas, indicating that the signaling pathway requires a TNF-R55-specific but death domain-independent signal. Indeed, using L929 cells that express mutant TNF-R55, we showed that the membrane-proximal region of TNF-R55 was essential for signaling to mitochondrial translocation. In the absence of translocation, the cell death response was markedly delayed, pointing to a cooperative effect on cell death. Translocation of mitochondria, although dependent on the microtubules, was not imposed by the latter and was equally induced by TNF-independent immunoinhibition of the motor protein kinesin. Additionally, immunoinhibition with antibody directed against the tail domain of kinesin synergized with TNF-induced cell death. Based on this functional mimicry, we propose that a TNF-R55 membrane-proximal region-dependent signal impedes mitochondria-associated kinesin, resulting in cooperation with the TNF-R55 death domain-induced cytotoxic response and causing the observed clustering of mitochondria.


Legal duties of physicians.
The history of the physician's legal duties has been traced from the first recorded writings of the Babylonian era to the present day. There has been a transition from the days of absolute liability to the modern idea of liability based on culpability. The doctrine of stare decisis developed in early English law forms the very backbone of our own jurisprudence.Broadly, if a physician renders reasonable care and skill, he is absolved from liability. Some of the more important legal duties and proscriptions applying to physicians are discussed in particular in this presentation.


Fructose-rich niches traced the evolution of lactic acid bacteria toward fructophilic species.
Fructophilic lactic acid bacteria (FLAB) are found in fructose-rich habitats associated with flowers, fruits, fermented foods, and the gastrointestinal tract of several insects having a fructose-based diet. FLAB are heterofermentative lactobacilli that prefer fructose instead of glucose as carbon source, although additional electron acceptor substrates (e.g. oxygen) remarkably enhance their growth on glucose. As a newly discovered bacterial group, FLAB are gaining increasing interest. In this review, the ecological context in which these bacteria exist and evolve was resumed. The wide frequency of isolation of FLAB from fructose feeding insects has been deepened to reveal their ecological significance. Genomic, metabolic data, reductive evolution, and niche specialization of the main FLAB species have been discussed. Findings to date acquired are consistent with a metabolic model in which FLAB display a reliance on environmental niches and the degree of host specificity. In light of FLAB proximity to lactic acid bacteria generally considered to be safe, and due to their peculiar metabolic traits, FLAB may be successfully exploited in food and pharmaceutical applications.


A comparison of the blood levels and urinary excretion of ethionamide and prothionamide in man.
The blood levels and urinary excretion of the anti-mycobacterial drugs ethionamide and prothionamide have been compared after oral dosage in man. High pressure liquid chromatographic methods were used to determine the two closely related thioamides and their microbiologically active sulphoxide metabolites after the ingestion of both single and combined doses of the two drugs. Both drugs were rapidly eliminated from the body, the half-life for the urinary excretion and removal from the plasma of prothionamide being slightly less than that of ethionamide. Less than 0.1% of the orally administered doses were excreted unchanged in the faeces. Plasma concentrations of ethionamide and its sulphoxide metabolite were substantially higher than those of prothionamide and prothionamide sulphoxide. The implications of these findings for the use of ethionamide or prothionamide in the treatment of lepromatous leprosy are discussed.


Quasi-one-dimensional magnons in an intermetallic marcasite.
We present inelastic neutron scattering measurements and first principles calculations examining the intermetallic marcasite CrSb(2). The observed spin-wave dispersion implies that the magnetic interactions are strongly one-dimensional with antiferromagnetic chains parallel to the crystalline c axis. Such low-dimensional excitations are unexpected in a semiconducting intermetallic system. Moreover, we observe a clear anisotropic thermal conductivity indicating that the magnetic anisotropy enhances thermoelectric properties along particular crystallographic directions.


Regulation of gamma-aminobutyric acidA receptor subunit expression by activation of N-methyl-D-aspartate-selective glutamate receptors.
Exposure of primary cultures of rat cerebellar granule cells to specific antagonists of the N-methyl-D-aspartate (NMDA)-selective glutamate receptor reduces the steady state levels of mRNAs encoding various gamma-aminobutyric acidA (GABAA) receptor subunits. These neurons are glutamatergic and require a depolarizing concentration of K+ (25 mM) for optimal development and survival. When the neuronal differentiation rate is retarded by lowering of the extracellular [K+] (to 12.5 mM), a persistent stimulation of the same glutamate receptors with nonneurotoxic doses of NMDA increases the expression of these GABAA receptor subunits. This suggests that the lowered K+ concentration reduces neuronal depolarization and the consequent release of glutamate from the cells. These results show that the neuronal content of selected GABAA receptor subunit mRNAs is optimized by certain levels of glutamate in the culture medium, suggesting a neurotrophic action of this neurotransmitter at certain developmental stages of granule cells in culture.


Variation in presentation and presence of DNA adducts and p53 mutations in patients with endemic nephropathy--an environmental form of the aristolochic acid nephropathy.
Endemic nephropathy (EN) and associated urothelial cell cancers (UUC) are an environmental form of aristolochic acid nephropathy where the most probable rout of ingestion of aristolochic acid (AA) was made by bread contaminated with AA, leading to chronic dietary intoxication. Clinical courses of three members of the same family, similarly exposed to toxin, who exhibited different clinical courses of the disease are presented. Questionnaires on AA exposure were taken. Tissue samples were obtained during therapeutic nephrouretectomies. Histopathology, immunohistochemical detection of p53, p53 mutation screening in tumor DNA and analysis on the presence of aristolactam (AL)-DNA adducts were performed. Case 1 had UUC with typical EN histopathological signs, whereas Case 2 had bilateral UUCs with typical EN histopathological signs. In contrast, the patient in Case 3 initially showed renal insufficiency, complicated afterwards by right UUC, and later on by left UUC with histopathological end-stage chronic changes but without typical EN changes. AA-DNA adducts and specific p53 mutational spectra (A:T→ T:A transversion) were found in tissues of cases 1 and 2. Diverse clinical courses seem to be related not to differences in exposure but to differences in metabolic activation or detoxification of AA and/or DNA repair resulting from different genetic polymorphisms.


PHREND®-A Real-World Data-Driven Tool Supporting Clinical Decisions to Optimize Treatment in Relapsing-Remitting Multiple Sclerosis.
With increasing availability of disease-modifying therapies (DMTs), treatment decisions in relapsing-remitting multiple sclerosis (RRMS) have become complex. Data-driven algorithms based on real-world outcomes may help clinicians optimize control of disease activity in routine praxis. We previously introduced the PHREND® (Predictive-Healthcare-with-Real-World-Evidence-for-Neurological-Disorders) algorithm based on data from 2018 and now follow up on its robustness and utility to predict freedom of relapse and 3-months confirmed disability progression (3mCDP) during 1.5 years of clinical practice. The impact of quarterly data updates on model robustness was investigated based on the model's C-index and credible intervals for coefficients. Model predictions were compared with results from randomized clinical trials (RCTs). Clinical relevance was evaluated by comparing outcomes of patients for whom model recommendations were followed with those choosing other treatments. Model robustness improved with the addition of 1.5 years of data. Comparison with RCTs revealed differences <10% of the model-based predictions in almost all trials. Treatment with the highest-ranked (by PHREND®) or the first-or-second-highest ranked DMT led to significantly fewer relapses (p < 0.001 and p < 0.001, respectively) and 3mCDP events (p = 0.007 and p = 0.035, respectively) compared to non-recommended DMTs. These results further support usefulness of PHREND® in a shared treatment-decision process between physicians and patients.


School and Community Influences on the Long Term Post-Disaster Recovery of Children and Youth Following Hurricane Georges.
Disasters affect the school and community microsystems in which children and youth recover. This study explored characteristics of the school (school violence, teachers' attitudes) and community microsystem (neighborhood climate, neighborhood monitoring, community violence) that may affect the disaster exposure and internalizing psychopathology relationship in children and youth 12-27 months after Hurricane Georges hit Puerto Rico. A representative sample (N=1,637) of caregivers and children/youth completed structured interviews in Spanish. Controlling for gender and perception of poverty, for children (age 6-10 years), hurricane exposure increased risk for internalizing psychopathology, but the school and community variables did not have an influence. For all youth (age 11-17 years), witnessing community violence and poor teacher attitudes increased the risk of psychopathology. In addition, neighborhood climate and school violence were moderators. For non-exposed youth, poor neighborhood climate and perceiving greater school violence increased the risk of internalizing psychopathology, whereas for exposed youth it did not.


IL-12 protects bone marrow from and sensitizes intestinal tract to ionizing radiation.
IL-12, a potent stimulator of hemopoietic progenitor cells, was evaluated as a potential protector against 60Co-gamma radiation-induced lethal hemopoietic syndrome in mice. Administration of IL-12 before lethal irradiation of genetically distinct strains of mice, B6D2F1 and C3H/HeJ, protected a significant fraction of both strains of mice from death. Radioprotection was associated with a fivefold increase in the number of bone marrow cells at 6 days after irradiation. Even at supralethal doses of radiation (1200 cGy), the number of c-kit+ bone marrow cells 3 days after irradiation was twofold greater in IL-12-treated mice than in saline-treated mice. However, mice that received IL-12 and 1200 cGy (B6D2F1) or 900 cGy (C3H/HeJ) died of the gastrointestinal syndrome, as was evident by gross necroscopy and histologic evaluation, within 4 to 6 days after irradiation. Induction of the gastrointestinal syndrome in mice not treated with IL-12 required radiation doses of 1500 cGy or greater in both strains. Thus, at doses of radiation at which IL-12 still protects c-kit+ hemopoietic cells, it sensitizes the intestinal tract to damage. Radioprotection with IL-12 was abrogated by anti-IL-1R or anti-stem cell factor Ab. Anti-IFN-gamma Ab did not affect IL-12-induced hemopoietic radioprotection, but abrogated sensitization of the intestinal tract by IL-12. The sensitizing effect of IL-12 may be related to its ability to prime mice to subsequent inflammatory challenge, as demonstrated by an almost 100-fold increase in circulating TNF and IL-6 levels in normal B6D2F1 mice challenged with IL-12 and LPS. This priming effect of IL-12 also was abrogated by anti-IFN-gamma Ab.


Mixed Meal Tolerance Test Versus Continuous Glucose Monitoring for an Effective Diagnosis of Persistent Post-Bariatric Hypoglycemia.
Gastric bypass determines an increase in incretin secretion and glucose excursions throughout the day and may sometimes entail the development of severe post-bariatric hypoglycemia (PBH). However, there is no consensus on the gold standard method for its diagnosis. In this study, we evaluated the usefulness of a mixed meal tolerance test (MMTT) and continuous glucose monitoring (CGM) for the diagnosis of PBH, defined as glucose levels <54 mg/dL (3.0 mmol/L). We found that hypoglycemia occurred in 60% of patients after the MMTT and in 75% during CGM, and it was predominantly asymptomatic. The MMTT confirmed the diagnosis of PBH in 88.9%of patients in whom surgery had been performed more than three years ago, in comparison to 36.4% in cases with a shorter postsurgical duration. CGM diagnosed nocturnal asymptomatic hypoglycemia in 70% of patients, and daytime postprandial hypoglycemia in 25% of cases. The mean duration of asymptomatic hypoglycemia was more than 30 min a day. Patients with ≥2% of their CGM readings with hypoglycemia exhibited a higher degree of glucose variability than those with <1% of the time in hypoglycemia. Our results show that the MMTT may be a useful dynamic test to confirm the occurrence of hypoglycemia in a large number of patients with persistent and recurrent PBH during long-term follow-up after gastric bypass. CGM, on its part, helps identify hypoglycemia in the real-world setting, especially nocturnal asymptomatic hypoglycemia, bringing to light that PBH is not always postprandial.


Standardization and interlaboratory reproducibility assessment of pulsed-field gel electrophoresis-generated fingerprints of Acinetobacter baumannii.
A standard procedure for pulsed-field gel electrophoresis (PFGE) of macrorestriction fragments of Acinetobacter baumannii was set up and validated for its interlaboratory reproducibility and its potential for use in the construction of an Internet-based database for international monitoring of epidemic strains. The PFGE fingerprints of strains were generated at three different laboratories with ApaI as the restriction enzyme and by a rigorously standardized procedure. The results were analyzed at the respective laboratories and also centrally at a national reference institute. In the first phase of the study, 20 A. baumannii strains, including 3 isolates each from three well-characterized hospital outbreaks and 11 sporadic strains, were distributed blindly to the participating laboratories. The local groupings of the isolates in each participating laboratory were identical and allowed the identification of the epidemiologically related isolates as belonging to three clusters and identified all unrelated strains as distinct. Central pattern analysis by using the band-based Dice coefficient and the unweighted pair group method with mathematical averaging as the clustering algorithm showed 95% matching of the outbreak strains processed at each local laboratory and 87% matching of the corresponding strains if they were processed at different laboratories. In the second phase of the study, 30 A. baumannii isolates representing 10 hospital outbreaks from different parts of Europe (3 isolates per outbreak) were blindly distributed to the three laboratories, so that each laboratory investigated 10 epidemiologically independent outbreak isolates. Central computer-assisted cluster analysis correctly identified the isolates according to their corresponding outbreak at an 87% clustering threshold. In conclusion, the standard procedure enabled us to generate PFGE fingerprints of epidemiologically related A. baumannii strains at different locations with sufficient interlaboratory reproducibility to set up an electronic database to monitor the geographic spread of epidemic strains.


Comparison of Orientation Mapping in SEM and TEM.
Multiple experimental configurations for performing nanoscale orientation mapping are compared to determine their fidelity to the true microstructure of a sample. Transmission Kikuchi diffraction (TKD) experiments in a scanning electron microscope (SEM) and nanobeam diffraction (NBD) experiments in a transmission electron microscope (TEM) were performed on thin electrodeposited hard Au films with two different microstructures. The Au samples either had a grain size that is >50 or <20 nm. The same regions of the samples were measured with TKD apparatuses at 30 kV in an SEM with detectors in the horizontal and vertical configurations and in the TEM at 300 kV. Under the proper conditions, we demonstrate that all three configurations can produce data of equivalent quality. Each method has strengths and challenges associated with its application and representation of the true microstructure. The conditions needed to obtain high-quality data for each acquisition method and the challenges associated with each are discussed.


Idiopathic infantile chronic rhegmatogenous retinal detachment.
The authors describe a 3-month-old female infant with infantile rhegmatogenous retinal detachment with no associated congenital or developmental abnormalities. The unique presentation of this patient indicates that the detachment was a result of an early developmental defect.


Anticipating the clinical adoption of regenerative medicine: building institutional readiness in the UK.
This perspective paper examines the challenges of implementing regenerative medicine (RM) therapies within hospitals and clinics. Drawing on recent work in the social sciences, the paper highlights dynamics within existing healthcare systems that will present both hindrances and affordances for the implementation of new RM technologies within hospitals and clinics. The paper argues that identifying suitable locations for cell- and gene-therapy treatment centers requires an assessment of their institutional readiness for RM. Some provisional criteria for assessing institutional readiness are outlined, and the paper will suggest that it is necessary to begin developing a program for the phased introduction of RM in the longer term.


Potential use of silkworm gut fiber braids as scaffolds for tendon and ligament tissue engineering.
Tendon and ligament tissue engineering require scaffolds for the treatment of various conditions in the medical field. These must meet requirements such as high tensile strength, biocompatibility, fast and stable repair and a rate of degradation that allows the repair of the damaged tissue. In this work, we propose the use of silkworm gut fiber braids as materials to temporarily replace and repair this type of tissues. The mechanical characterization of the braids made with different number of silk gut fibers is provided, as well as a descriptive analysis of the proliferation and adhesion of cultures of adult human mesenchymal stem cells from bone marrow and fibroblasts (L929) on the braids. As expected, the breaking force increases linearly in the scaffold with the number of fibers, thus being a parameter adaptable to the specific requirements of the tissue to repair and the animal model of study. On the other hand, in all of the cases studied, the values obtained for the elastic modulus of the hydrated fibers were in the range of the ones reported for various human tendons and ligaments. Moreover, the scaffold demonstrated excellent biocompatibility in vitro, allowing the adhesion and proliferation, in the same culture conditions, of the two cell types studied, therefore posing as an ideal candidate to be employed in future in vivo studies that allow elucidating its behavior in the articular environment or extra-articular tendinous areas. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: 2019. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2209-2215, 2019.


Therapeutic advancement of simvastatin-loaded solid lipid nanoparticles (SV-SLNs) in treatment of hyperlipidemia and attenuating hepatotoxicity, myopathy and apoptosis: Comprehensive study.
This study set out to optimize simvastatin (SV) in lipid nanoparticles (SLNs) to improve bioavailability, efficacy and alleviate adverse effects. Simvastatin-loaded solid lipid nanoparticles (SV-SLNs) were prepared by hot-melt ultrasonication method and optimized by box-Behnken experimental design. Sixty Wister albino rats were randomly assigned into six groups and treated daily for 16 weeks: control group, the group fed with 20 g of high-fat diet (HFD), group treated with vehicle (20 mg/kg, P.O.) for last four weeks, group treated with HFD and SV (20 mg/kg, P.O.) / or SV-SLNs (20 mg/kg/day, P.O.) / or SV-SLNs (5 mg/kg, P.O.) at last four weeks. Blood, liver tissues, and quadriceps muscles were collected for biochemical analysis, histological and immunohistochemical assays. The optimized SV-SLNS showed a particle-size 255.2 ± 7.7 nm, PDI 0.31 ± 0.09, Zeta-potential - 19.30 ± 3.25, and EE% 89.81 ± 2.1%. HFD showed severe changes in body weight liver functions, lipid profiles, atherogenic index (AIX), albumin, glucose, insulin level, alkaline phosphatase as well as muscle injury, oxidative stress biomarkers, and protein expression of caspase-3. Simvastatin treatment in animals feed with HFD showed a significant improvement of all tested parameters, but it was associated with hepatotoxicity, myopathy, and histological changes in quadriceps muscles. SV-SLNs exhibited a significant improvement of all biochemical, histological examinations, and immunohistochemical assays. SV-SLNs (5 mg/kg) treatment returns all measured parameters to control itself. These results represent that SV-SLNs is a promising candidate as a drug carrier for delivering SV with maximum efficacy and limited adverse reaction.


Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia.
miRNA (miR) 34a has been shown to modulate critical gene transcripts involved in tumorigenesis, but its role in tumor-mediated immunosuppression is largely unknown. PD-L1 plays an important role in immune responses, however, presently its transcriptional regulatory mechanisms are not well understood. In the present study, we analyzed the expression of PD-L1 and miR-34a in 44 acute myeloid leukemia (AML) samples, and observed an inverse correlation between PD-L1 and miR-34a expression. Overexpression of miR-34a in HL-60 and Kasumi-1 cells blocked PD-L1 expression, and reduced PD-L1 surface expression. Using luciferase reporter assay and mutagenesis, we identified miR-34a as a putative binder of the PD-L1-3'UTR. Surface expression of PD-L1 induced by chemotherapeutic agents could also be reversed by miR-34a; furthermore, PD-L1 specific T cell apoptosis was reduced as well following miR-34a transfection. We also found that there is a positive feedback between PD-L1 expression and AKT activation. Our data suggest that miR-34a can regulate PD-L1 expression by targeting PD-L1 mRNA, and our present findings shed new light on the complex regulation of PD-L1 in human tumors, and on miR-34a in cancer immuno-based therapy.


[The robotic surgeon training].
The widespread robotic surgery in the world highlighted the relevance of the training programs for young urologists and residents. In the last years, urologic societies and some independent robotic surgeons strongly worked to standardize some general and specific training modules. Theoretical and practical sections of robotic training programs have been recently specified. The role of simulators, dry and wet laboratories, bedside assistance, and modular (step-by-step) training at console represent the most relevant elements of robotic surgeon training. Ideally, these didactic tools should be available in modern training centers. The development of structured robotic training programs should be considered as one of the priorities that the urologic community must take into account in the near future.


Human Enterovirus 71 Protein Displayed on the Surface of Saccharomyces cerevisiae as an Oral Vaccine.
Human enterovirus 71 (EV-A71), a major agent of hand, foot, and mouth disease, has become an important public health issue in recent years. No effective antiviral or vaccines against EV-A71 infection are currently available. EV-A71 infection intrudes bodies through the gastric mucosal surface and it is necessary to enhance mucosal immune response to protect children from these pathogens. Recently, the majority of EV-A71 vaccine candidates have been developed for parenteral immunization. However, parenteral vaccine candidates often induce poor mucosal responses. On the other hand, oral vaccines could induce effective mucosal and systemic immunity, and could be easily and safely administered. Thus, proper oral vaccines have attached more interest compared with parenteral vaccine. In this study, the major immunogenic capsid protein of EV-A71 was displayed on the surface of Saccharomyces cerevisiae. Oral immunization of mice with surface-displayed VP1 S. cerevisiae induced systemic humoral and mucosal immune responses, including virus-neutralizing titers, VP1-specific antibody, and the induction of Th1 immune responses in the spleen. Furthermore, oral immunization of mother mice with surface-displayed VP1 S. cerevisiae conferred protection to neonatal mice against the lethal EV-A71 infection. Furthermore, we observed that multiple boost immunization as well as higher immunization dosage could induce higher EV-A71-specific immune response. Our results demonstrated that surface-displayed VP1 S. cerevisiae could be used as potential oral vaccine against EV-A71 infection.


Resveratrol Inhibition of Renal Cancer Stem Cell Characteristics and Modulation of the Sonic Hedgehog Pathway.
Renal cell cancers typically exhibit high metastasis and recurrence, and this is thought to be due to renal cancer stem cells (CSCs). Meanwhile, aberrant activation of Sonic hedgehog (Shh) signaling is linked with CSCs. Resveratrol has direct or indirect impacts on the pathological activities of CSCs. However, the effects of resveratrol on renal CSCs remain to be elucidated. We cultured renal CSCs in serum-free medium. Western blotting was used to analyze the expression levels of related proteins. The mRNA changes were detected by qRT-PCR after resveratrol treatment. The CD133+ cells were quantified by flow cytometry analysis. Immunofluorescence staining images showed the changes in CD44 and Smoothened expression in the cell spheres. Renal CSCs were enriched by tumorsphere formation assays of ACHN and 786-O cells. Resveratrol treatments markedly decreased the size and number of cell spheres and downregulated the expression of the Shh pathway-related proteins and CSCs markers. Moreover, we observed that resveratrol inhibited cell proliferation and induced cell apoptosis, while purmorphamine upregulated the Shh pathway and weakened the effects of resveratrol on renal CSCs. These results suggested that resveratrol is a potential novel therapeutic agent that targets inactivation of renal CSCs by affecting the function of the Shh pathway.


Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans.
Methylmercury (MeHg) is a persistent environmental and dietary contaminant that causes serious adverse developmental and physiologic effects at multiple cellular levels. In order to understand more fully the consequences of MeHg exposure at the molecular level, we profiled gene and miRNA transcripts from the model organism Caenorhabditis elegans. Animals were exposed to MeHg (10 μM) from embryo to larval 4 (L4) stage and RNAs were isolated. RNA-seq analysis on the Illumina platform revealed 541 genes up- and 261 genes down-regulated at a cutoff of 2-fold change and false discovery rate-corrected significance q < 0.05. Among the up-regulated genes were those previously shown to increase under oxidative stress conditions including hsp-16.11 (2.5-fold), gst-35 (10.1-fold), and fmo-2 (58.5-fold). In addition, we observed up-regulation of 6 out of 7 lipocalin related (lpr) family genes and down regulation of 7 out of 15 activated in blocked unfolded protein response (abu) genes. Gene Ontology enrichment analysis highlighted the effect of genes related to development and organism growth. miRNA-seq analysis revealed 6-8 fold down regulation of mir-37-3p, mir-41-5p, mir-70-3p, and mir-75-3p. Our results demonstrate the effects of MeHg on specific transcripts encoding proteins in oxidative stress responses and in ER stress pathways. Pending confirmation of these transcript changes at protein levels, their association and dissociation characteristics with interaction partners, and integration of these signals, these findings indicate broad and dynamic mechanisms by which MeHg exerts its harmful effects.


A new congenital form of X-linked autophagic vacuolar myopathy.
In a new family with X-linked congenital autophagic vacuolar myopathy (AVM), seven affected boys presented with congenital hypotonia, dyspnea, and dysphagia with delayed motor milestones. Muscle pathology revealed autophagic vacuoles with sarcolemmal features, multilayered basal lamina with marked sarcolemmal deposition of C5-9 membrane attack complex and calcium, histologically indistinguishable from childhood-onset X-linked myopathy with excessive autophagy (XMEA). Haplotype analysis suggests that this new AVM and XMEA may be allelic despite different clinical presentations.


Larvicidal activity of Bacillus thuringiensis subsp. israelensis in the dipteran Haematobia irritans.
A strain of Bacillus thuringiensis subsp. israelensis was found to be larvicidal to horn flies, Haematobia irritans (L. [Diptera:Muscidae]). The toxic activity was particulate, appeared during sporulation, and could be prevented by the addition of streptomycin before sporulation. Density gradient centrifugation in Renografin was used to separate endospores, crystals, and low-density particulate matter (fraction 3) from sporulated preparations. Larvicidal activity was restricted to purified crystals and fraction 3, indicating that delta-endotoxin of B. thuringiensis subsp. israelensis was active against horn fly larvae. Purified crystals produced mortality during larval feeding stages, but not pupal stages. Fraction 3 produced significant mortality during both larval and pupal stages. The mortality data indicated the presence of at least two dipteran-active toxins.


Appearance of Ankylosing Spondylitis in a Middle-Aged Female Patient With a Long History of Rheumatoid Arthritis.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial bones, primarily affecting the spine. AS is classified as spondyloarthritis because it affects the spine and other joints. AS has several presentations and, in some cases, can be insidious, making it difficult to diagnose. We encountered a patient on long-term follow-up for rheumatoid arthritis with an appearance of AS. This case suggests that patients with long-term rheumatoid arthritis can develop AS during follow-up and that the seropositivity of rheumatoid factors and anti-cyclic citrullinated peptide antibodies cannot rule out AS. Therefore, the possibility of AS should be considered, even in patients diagnosed with rheumatoid arthritis.


Extraosseus Ewing's Sarcoma in Pancreas: A Review.
Primitive neuroectodermal tumors (PNET, previously referred to as peripheral neuroepithelioma) are rare malignant tumors with various degrees of differentiation belonging to the Ewing's family of sarcomas. They are classified as round cell tumors arising from soft tissues. In rare instances, PNETs may arise from solid organs containing neuroendocrine cells of kidney, bladder, heart, lungs, parotid glands and pancreas. Most cases occur in the second decade of life with a slight preponderance in males. PNET of the pancreas is an aggressive tumor with multiple recurrences and a relatively poor prognosis. These tumors should be considered in the differential diagnosis, especially in a diagnosed pancreatic tumor in individuals less than 35 years of age. Due to the nature of the tumor, surgery with subsequent chemoradiation are widely accepted modalities despite the poor prognosis. In this article, we review 25 cases of extraosseous Ewing's sarcoma (ES) of the pancreas which to the best of our knowledge, enlists most cases reported in the literature thus far.


Systematic considerations in the area of multiple chemical sensitivity.
Many workers who speculate about multiple chemical sensitivity (MCS) have devised a large number of hypothetical constructs designed to explain the phenomena. Too often these are not logically connected to the larger body of scientific thought but instead appeal to ideas not documented in accessible literature and often appearing metaphysical in nature.


Upper eyelid levator-recession and anterior lamella repositioning through the grey-line: Avoiding a skin-crease incision.
This study aims to report a case series of upper eyelid cicatricial margin entropion with retraction, corrected through a grey-line approach only. We remind readers of the grey-line approach to levator recession (LR) and lamellar repositioning surgery. A retrospective review of clinic notes and photographs of patients who underwent grey-line split (GLS), LR, release of orbital septum, recession of levator, advancement of posterior lamella and anterior lamellar repositioning without a skin crease incision, from December 2015 to December 2016. Indications for surgery included mild-to-moderate cicatricial margin upper eyelid entropion, tarsal curling, and meibomian gland inversion. Patients requiring spacer interposition to lengthen the posterior lamella were excluded from the study. Parameters of the study included lid margin position, lid height, ocular surface health and symptom improvement. Eleven eyelids of eight patients were included in the study, and underwent the procedure described. Lid margin position measured as the marginal reflex distance lowered (improved) in 72.7% of patients. Lid margin eversion was achieved in all eyes (100%). Corneal punctate epithelial erosions markedly improved, being present in 72.7% of patients preoperatively, and only 9.1% of patients postoperatively. Eight of eleven eyes showed symptomatic improvement, with six (54.5%) being completely asymptomatic and two achieving partial relief. An added observation was a pretarsal show asymmetry in some patients which improved in 36.4% of surgeries postoperatively. Upper eyelid LR with GLS and anterior lamella repositioning can all be performed through the plane of the split, avoiding a skin incision. Normal lid margin apposition was achieved in all eyes with 91% demonstrating a clear cornea and 72% having symptomatic improvement.


Exploring Cerebrospinal Fluid IgG N-Glycosylation as Potential Biomarker for Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which the existing candidate biomarkers (neurofilaments) have low specificity. Changes in blood IgG N-glycosylation have been observed in several diseases, including ALS, whereas cerebrospinal fluid (CSF) IgG has been less studied. Here, we characterized N-glycans of CSF IgG from ALS patients in comparison with a control group of other neurological diseases. Cerebrospinal fluid was collected from patients with ALS (n = 26) and other neurological diseases (n = 10). N-Glycans were released from CSF purified IgG with peptide N-glycosidase F, labeled with 2-aminobenzamide and analyzed by NP-HPLC chromatography in combination with exoglycosidase digestion and MALDI-TOF mass spectrometry. The N-glycosylation profile of ALS CSF IgG consisted of diantennary N-glycans predominantly with proximal fucose and some bisecting GlcNAc; agalacto-, mono-, and digalactosylated as well as α2,6-sialylated structures were detected. Differences between ALS and control patients were observed; most relevant was the increase in ALS CSF IgG of the level of galactosylated structures defined here as Gal-index (median 46.87 and 40.50% for ALS and controls, respectively; p = 0.006). The predictive value of the Gal-index (AUC = 0.792, p = 0.007) considering ROC analysis had potential utility as a diagnostic test for ALS and was comparable to that of phosphoneurofilament heavy chain (AUC = 0.777, p = 0.011), which was used as benchmark marker for our group of patients. The results provide the basis to further explore the potential of IgG N-glycan galactosylation as biomarker for ALS by using larger cohorts of patients and controls.


Nano-zero valent iron impregnated cashew nut shell: a solution to heavy metal contaminated water/wastewater.
The present research is focused on the removal of Zn(II) ions from aqueous solution using nano zero-valent iron impregnated cashew nut shell (NZVI-CNS). The present system was investigated in batch mode operation. NZVI-CNS was prepared by the liquid-phase reduction process. The results showed that the NZVI-CNS exhibited superior adsorption capacity for the removal of Zn(II) ions. Adsorption isotherm and kinetic models were applied to explain the nature of the adsorption process. Adsorption kinetic data followed the pseudo-first order kinetic model. Moreover, the equilibrium adsorption data were best fitted with a Freundlich model. Langmuir monolayer adsorption capacity was calculated as 94.46 mg of Zn(II) ions/g of NZVI-CNS. The thermodynamic parameters explain that the present adsorption system was measured as feasible and spontaneous. This newly prepared adsorbent can be successfully applied for the different industrial wastewater treatment. Finally, the exploration asks about contemplated that NZVI-CNS has exhibited unrivalled adsorption limit. Additionally, NZVI-CNS is believed to be extremely green and monetarily neighbourly help for wastewater treatment. The results indicate that the feasible approach could be applied in agricultural waste biomass materials for the productive expulsion of heavy metals from aqueous solution and reusing agricultural wastes to facilitate their disposal problem.


Analysis of Differentially Expressed Proteins in Mycobacterium avium-Infected Macrophages Comparing with Mycobacterium tuberculosis-Infected Macrophages.
Mycobacterium avium (MA) belongs to the intracellular parasitic bacteria. To better understand how MA survives within macrophages and the different pathogenic mechanisms of MA and Mycobacterium tuberculosis (MTB), tandem mass tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis have been used to determine the proteins which are differentially expressed in MA-infected and MTB-infected macrophages. 369 proteins were found to be differentially expressed in MA-infected cells but not in MTB-infected cells. By using certain bioinformatics methods, we found the 369 proteins were involved in molecular function, biological process, and cellular component including binding, catalytic activity, metabolic process, cellular process, and cell part. In addition, some identified proteins were involved in multiple signaling pathways. These results suggest that MA probably survive within macrophages by affecting the expression of some crucial proteins.