The evaluation of MRSA surveillance cultures by the number and combinations of anatomical sites.
The identification of patients infected and/or colonised by methicillin resistant Staphylococcus aureus (MRSA) is necessary for the timely introduction of measures for infection control. We compared the diagnostic efficacy of combinations of MRSA surveillance swabs routinely taken by health institutions in the country. All surveillance samples, which were sent for a microbiological analysis to detect MRSA with the culture method in 2014, in the three departments for medical microbiology of the National Laboratory for Health, Environment and Food, were included in this study. Among 65,251 surveillance cultures from 13,274 persons, 1,233 (2.1%) were positive (490 positive persons). Prevailing positive surveillance cultures were throat swabs (31.3%), followed by nose swab (31.2%), skin swab (18.9%), perineum (16.4%) and wound swabs (1.4%). The contribution of other samples, such as aspirate, urine and excreta, was under 1%. We found no statistically significant differences in the frequency of detection of a positive patient, if the combination of samples NTS (nose, throat, skin) or NTP (nose, throat, perineum) was analysed. However, statistically significant differences were confirmed when any of the anatomic sites would be omitted from the sets of NTP and NTS (chi square; p<0.01). Adding additional samples resulted in only 24 additional positive patients (4.9%). The results indicate that increasing the number of surveillance cultures above three does not add much to the sensitivity of MRSA surveillance, the exception could be wound. The swabs from the perineum and from the skin are exchangeable.


Abnormalities in the content of nucleic acids of peripheral blood mononuclear cells from patients with systemic lupus erythematosus.
We have completed 59 cytofluorographic studies of DNA/RNA content in acridine orange-stained peripheral blood mononuclear cells from 44 patients with systemic lupus erythematosus, most of whom received no medications. Most such cells were in resting phases of the cell cycle, particularly those from patients with inactive disease. Nine patients with systemic lupus erythematosus had increased percentages of these cells in the synthesis and postsynthesis phases of the cell cycle; the B lymphocyte had a greatest proportions of activated cells. In 11 patients, we found that cells, particularly T lymphocytes, had increased RNA content without a proportional increase in DNA. This DNA block occurred primarily in patients with serum antibodies to DNA and it could be reproduced in normal mitogen-stimulated mononuclear cells incubated in heat-inactivated sera from patients with systemic lupus erythematosus whose own cells showed abnormalities of DNA/RNA content or in purified native DNA antibody. The DNA blocking potential of the DNA antibody was dependent on its Fc portion and on the presence of Fc receptors on T cells. Thus, saturation of Fc receptors by pretreatment with aggregated IgG or incubation with the whole antibody in the cold prevented the DNA block, indicating that it was an active process.


THE ORIGIN OF WEST EUROPEAN SUBSPECIES OF HONEYBEES (APIS MELLIFERA): NEW INSIGHTS FROM MICROSATELLITE AND MITOCHONDRIAL DATA.
Apis mellifera is composed of three evolutionary branches including mainly African (branch A), western and northern European (branch M), and southeastern European (branch C) populations. The existence of morphological clines extending from the equator to the Polar Circle through Morocco and Spain raised the hypothesis that the branch M originated in Africa. Mitochondrial DNA analysis revealed that branches A and M were characterized by highly diverged lineages implying very remote links between both branches. It also revealed that mtDNA haplotypes from lineages A coexisted with haplotypes M in the Iberian Peninsula and formed a south-north frequency cline, suggesting that this area could be a secondary contact zone between the two branches. By analyzing 11 populations sampled along a France-Spain/Portugal-Morocco-Guinea transect at 8 microsatellite loci and the DraI RFLP of the COI-COII mtDNA marker, we show that Iberian populations do not present any trace of "africanization" and are very similar to French populations when considering microsatellite markers. Therefore, the Iberian Peninsula is not a transition area. The higher haplotype A variability observed in Spanish and Portuguese samples compared to that found in Africa is explained by a higher mutation rate and multiple and recent introductions. Selection appears to be the best explanation to the morphological and allozymic clines and to the diffusion and maintenance of African haplotypes in Spain and Portugal.


Anti-erosion effect of an experimental varnish on eroded dentin.
This in vitro study evaluated the effect of an experimental varnish containing 20% nano-hydroxyapatite (nHAP) associated with 5% stannous chloride (SnCl2) against erosive-abrasive wear on bovine dentin. Samples of bovine cervical dentin were pre-eroded (0.3% citric acid, pH 2.6 for 10 minutes) and randomized into 4 groups (n=10): Control group - experimental varnish without active ingredient (CG); experimental varnish containing 20% nHAP (nHG); experimental varnish containing 5% SnCl2 (24.800 ppm Sn2+) (SnG); experimental varnish containing 20% nHAP associated with 5% SnCl2 (18.300 ppm Sn2+) (nHSnG). After applying the materials, the erosive-abrasive challenges were performed for five days. Erosive dentin loss and analysis of the pattern of dentinal obliteration were performed by 3D confocal laser microscopy. A one-way ANOVA/Bonferroni test was performed to analyze the data (α=0.05). The SnG and nHSnG experimental groups presented more effectiveness in preventing erosive wear when compared to the other groups (p<0.05). There was no statistically significant difference between the SnG and nHSnG groups (p = 0.731) in tooth structure dentin loss. Regarding the amount of open dentinal tubules, the highest amount of obstructed dentinal tubules was demonstrated in SnG and nHSnG (p < 0.05) when compared to the others. Between SnG and nHSnG there was no significant difference (p = 0.952) in the amount of closed dentinal tubules in the dentin. Experimental varnishes containing 5% SnCl2 associated or not with 20% nHAP showed to be a promising strategy in preventing erosive-abrasive wear of dentin. In addition, nHSnG was able to obliterate dentinal tubules.


Surface nitriding to improve the catalytic performance of FeNi3 for the oxygen evolution reaction.
Solving the problem of the slow kinetic process of the oxygen evolution reaction by electrocatalysts has attracted extensive attention. Here, we report an enhancement of the oxygen evolution reaction (OER) electrocatalytic activity via the surface nitriding of FeNi3 nanosheets for the formation of amorphous Fe/Ni-Nx species. The optimized Fe/Ni-Nx@FeNi3 nanosheets exhibit an overpotential of 251 mV to achieve a current density of 10 mA cm-2 and an excellent durability of 210 h. The superior electrocatalytic performance is attributed to the multi-component active sites, where the Fe/Ni-Nx outer layer inhibits metal active site leaching, and the catalyst undergoes dynamic reconfiguration during the OER.


Long-term survival after major trauma in geriatric trauma patients: the glass is half full.
The objective is to examine the long-term survival status of geriatric trauma patients (GTPs) after major trauma. A 10-year retrospective review at a Level I trauma center was performed. GTP were defined as age ≥ 65 years, with Injury Severity Score ≥ 30. Primary endpoints: survival at hospital discharge and long-term survival and discharge status. Two groups were defined: Abbreviated Injury Score (AIS) head >3 (G1, n = 116) and AIS head ≤ 3 (G2, n = 29). For GTP surviving hospitalization, two subgroups were defined: AIS head >3 (SG1, n = 77) and AIS head ≤ 3 (SG2, n = 20). Comparisons were analyzed for exploratory purposes only by independent t-tests or Mann-Whitney rank sums tests as appropriate. Long-term survival was plotted by a Kaplan-Meier curve. A total of 145 GTP met inclusion criteria. In-hospital mortality was 33%. Nonsurvivors had lower Glasgow Coma Scale score (6 vs. 14, p < 0.001), higher Injury Severity Score (38 vs. 34, p < 0.003), and lower Revised Trauma Score (5.97 vs. 7.84, p < 0.002). Hospital mortality for G1 was 34% (39 of 116) and for G2 was 31% (9 of 29). In group 1 (n = 116), 39 patients (34%) died while 77 (66%) survived a median of 29 months (interquartile range [IQR] = 6-62). In group 2 (n = 29), 9 patients (31%) died while 20 (69%) survived a median of 46.50 months (IQR = 26.75-79). For the 77 patients who were alive at discharge (subgroup 1, AIS >3), 25 (32%) died while 52 (68%) survived a median of 33 months (IQR = 10.50-72.75). For the 20 patients with AIS ≤ 3 (subgroup 2), 7 of 20 (35%) died while 13 (65%) survived a median of 49 months (IQR = 30.50-93.50). A total of 28 patients (19%) survived more than 5 years from the time of discharge. For these 65 GTPs who are currently alive at the time of follow-up, living status could be determined for 49 (75%) and 33 of 49 (67%) were living at home. This study documents appreciable long-term survival for GTP with major injury including severe head injury. A substantial proportion of these patients was able to return home. III, prognostic/epidemiological study.


Positive pressure technique for removal of nasal foreign bodies.
Nasal foreign bodies represent a common ENT problem in children. Ninety percent of these can be removed without otorhinolaryngologic intervention. Numerous documented techniques exist, employing instruments, which pose problems in children. Positive pressure technique avoids the need for instrumentation, therefore bypassing the disadvantages met by other techniques. Positive pressure technique is both safe and effective, highlighted by a success rate of 62.5% in 8 patients presenting acutely. Promising result of this small study warrantees further study in larger number of paediatric population. In contrast to previous documentation, children nursed prone tolerated the procedure better. Hollow objects were resilient to this technique and require other methods of removal. Positive pressure technique should be considered to remove foreign bodies from the paediatric nose especially in emergency department setting.


Torque and power-velocity relationships in cycling: relevance to track sprint performance in world-class cyclists.
The aims of the present study were both to describe anthropometrics and cycling power-velocity characteristics in top-level track sprinters, and to test the hypothesis that these variables would represent interesting predictors of the 200 m track sprint cycling performance. Twelve elite cyclists volunteered to perform a torque-velocity test on a calibrated cycle ergometer, after the measurement of their lean leg volume (LLV) and frontal surface area (A(p)), in order to draw torque- and power-velocity relationships, and to evaluate the maximal power (P(max)), and both the optimal pedalling rate (f(opt)) and torque (T(opt)) at which P (max) is reached. The 200 m performances--i.e. velocity (V200) and pedalling rate (f 200)--were measured during international events (REC) and in the 2002 French Track Cycling Championships (NAT). P(max), f(opt), and T(opt) were respectively 1600 +/- 116 W, 129.8 +/- 4.7 rpm and 118.5 +/- 9.8 N . m. P(max) was strongly correlated with T(opt) (p < 0.001), which was correlated with LLV (p < 0.01). V200 was related to P(max) normalized by A(p) (p < or = 0.05) and also to f(opt) (p < 0.01) for REC and NAT. f 200 (155.2 +/- 3, REC; 149 +/- 4.3, NAT) were significantly higher than f(opt) (p < 0.001). These findings demonstrated that, in this population of world-class track cyclists, the optimization of the ratio between P(max) and A(p) represents a key factor of 200 m performance. Concerning the major role also played by f(opt), it is assumed that, considering high values of f 200, sprinters with a high value of optimal pedalling rate (i.e. lower f200-f(opt) difference) could be theoretically in better conditions to maximize their power output during the race and hence performance.


Aspiration biopsy of carcinoma of the pancreas.
Peroperative pancreatic aspiration biopsies were performed on 21 patients with pancreatic lesions using a standard 20-ml disposable syringe and a 21-gauge needle. No complications were recorded which could be attributed to this procedure. A further 10 aspiration biopsies were carried out on postmortem specimens in an attempt to determine the accuracy of this method in the diagnosis of carcinoma of the pancreas. It is concluded that peroperative pancreatic needle biopsy is a safe procedure which is easily performed without special instruments. In can be of enormous value to the surgeon in planning the treatment of patients with pancreatic lesions. In cases where there is an operable mass in the pancreas it offers a simple and quick method of determining the presence of malignant cells and thus definitive surgery may be performed with confidence. For the inoperable cases it offers a method of histological confirmation of the operative findings.


Antral-ethmoidal decompression in Graves' disease. Five-year experience.
The orbital manifestations of Graves' disease frequently constitute the major and distressing portion of the morbidity in this poorly understood process. Patients with optic neuropathy, exposure keratopathy or disfiguring proptosis may be aided considerably by decompression to permit swollen orbital contents to move into the maxillary and ethmoid sinus cavities. Experience with 38 patients treated over a five-year period indicates that antral-ethmoidal decompression is a logical, successful form of therapy and generally free of serious complications. it may provide benefit earlier in the course of Graves' exophthalmopathy than has been accepted in the past.


Evaluating CD8⁺ T cell responses in vitro.
The (51)Cr-release assay described in the 1960s has been for decades the gold standard cytolytic assay and remains in use in many laboratories. Whereas other radioactive tests were later on described, they never fully replaced the (51)Cr-release assay. More thorough understanding of CTL biology and killing pathways has more recently resulted in the design of reliable nonradioactive tests to analyze CD8(+) T cell responses which are likely to supplant in a close future the (51)Cr-release assay.


Mountain medicine education in Europe.
All educational programs in mountain medicine in Europe are presented with their history, evolution, and current status. A comparison and a summary of those programs, as well as an estimate of the number of doctors trained in mountain medicine, are offered. Special focus is put on new developments and subspecialty programs. All programs listed in the Union Internationale des Associations Alpinistes (UIAA) information papers and all programs known through different publications were contacted and asked to forward information about recent courses, materials from former courses, and program syllabi. This information was reviewed and different specific topics were developed in depth. There are 13 different programs in Europe offering medical education in mountain medicine: 3 in France; 2 each in Italy, Spain, and the United Kingdom; and 1 each in Switzerland, Austria, Germany, and The Netherlands. The duration of these courses varies from a long weekend to a full 3-week course with theoretical and practical instruction. At this moment, most programs still have different contents and structures, which are being standardized by the UIAA and the International Commission for Alpine Rescue Medical Commission (ICAR MEDCOM). At least 2600 doctors have had a first-contact course in high-altitude medicine, and at least 2000 have participated in a full course of 1 week of more. A large number of doctors in Europe have become acquainted with mountain medicine by participating in different medical education programs. These programs should be optimized and further specialized in the different areas of mountain medicine, including expedition, alpine, and rescue medicine.


Mathematical models in genetics.
In this study, we present some of the basic ideas of population genetics. The founders of population genetics are R.A. Fisher, S. Wright, and J. B.S. Haldane. They, not only developed almost all the basic theory associated with genetics, but they also initiated multiple experiments in support of their theories. One of the first significant insights, which are a result of the Hardy–Weinberg law, is Mendelian inheritance preserves genetic variation on which the natural selection acts. We will limit to simple models formulated in terms of differential equations. Some of those differential equations are nonlinear and thus emphasize issues such as the stability of the fixed points and time scales on which those equations operate. First, we consider the classic case when selection acts on diploid locus at which wу can get arbitrary number of alleles. Then, we consider summaries that include recombination and selection at multiple loci. Also, we discuss the evolution of quantitative traits. In this case, the theory is formulated in respect of directly measurable quantities. Special cases of this theory have been successfully used for many decades in plants and animals breeding.


Viral Pathogen Detection by Metagenomics and Pan-Viral Group Polymerase Chain Reaction in Children With Pneumonia Lacking Identifiable Etiology.
Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalization. Pathogen identification fails in approximately 20% of children but is critical for optimal treatment and prevention of hospital-acquired infections. We used two broad-spectrum detection strategies to identify pathogens in test-negative children with CAP and asymptomatic controls. Nasopharyngeal/oropharyngeal (NP/OP) swabs from 70 children <5 years with CAP of unknown etiology and 90 asymptomatic controls were tested by next-generation sequencing (RNA-seq) and pan viral group (PVG) PCR for 19 viral families. Association of viruses with CAP was assessed by adjusted odds ratios (aOR) and 95% confidence intervals controlling for season and age group. RNA-seq/PVG PCR detected previously missed, putative pathogens in 34% of patients. Putative viral pathogens included human parainfluenza virus 4 (aOR 9.3, P = .12), human bocavirus (aOR 9.1, P < .01), Coxsackieviruses (aOR 5.1, P = .09), rhinovirus A (aOR 3.5, P = .34), and rhinovirus C (aOR 2.9, P = .57). RNA-seq was more sensitive for RNA viruses whereas PVG PCR detected more DNA viruses. RNA-seq and PVG PCR identified additional viruses, some known to be pathogenic, in NP/OP specimens from one-third of children hospitalized with CAP without a previously identified etiology. Both broad-range methods could be useful tools in future epidemiologic and diagnostic studies.


[Infections due to Legionella non-pneumophila].
Legionella species other than Legionella pneumophila may cause pneumonias and extrapulmonary infections. Most infections are nosocomial or observed in immunocompromised patients and often remain undiagnosed because of the failure of confirmatory culture methods. The therapy is based on macrolides and fluoroquinolones; rifampin and tetracycline are also used.


CD39/adenosine pathway is involved in AIDS progression.
HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS.


Flow-induced focal adhesion remodeling mediated by local cytoskeletal stresses and reorganization.
Cells respond to fluid shear stress through dynamic processes involving changes in actomyosin and other cytoskeletal stresses, remodeling of cell adhesions, and cytoskeleton reorganization. In this study we simultaneously measured focal adhesion dynamics and cytoskeletal stress and reorganization in MDCK cells under fluid shear stress. The measurements used co-expression of fluorescently labeled paxillin and force sensitive FRET probes of α-actinin. A shear stress of 0.74 dyn/cm(2) for 3 hours caused redistribution of cytoskeletal tension and significant focal adhesion remodeling. The fate of focal adhesions is determined by the stress state and stability of the linked actin stress fibers. In the interior of the cell, the mature focal adhesions disassembled within 35-40 min under flow and stress fibers disintegrated. Near the cell periphery, the focal adhesions anchoring the stress fibers perpendicular to the cell periphery disassembled, while focal adhesions associated with peripheral fibers sustained. The diminishing focal adhesions are coupled with local cytoskeletal stress release and actin stress fiber disassembly whereas sustaining peripheral focal adhesions are coupled with an increase in stress and enhancement of actin bundles. The results show that flow induced formation of peripheral actin bundles provides a favorable environment for focal adhesion remodeling along the cell periphery. Under such condition, new FAs were observed along the cell edge under flow. Our results suggest that the remodeling of FAs in epithelial cells under flow is orchestrated by actin cytoskeletal stress redistribution and structural reorganization.


Effect of gender on mitochondrial toxicity of Alzheimer's Abeta peptide.
The aim of this article is to review the role of mitochondria in the pathogenesis of Alzheimer's disease. Additionally, the effect of gender on the incidence of Alzheimer's disease and the pathophysiological mechanisms involved will be discussed. Mitochondria, in the presence of Alzheimer's amyloid-beta peptide, increase the formation of reactive oxygen species which act both as damaging agents and also as signaling molecules. These radicals, in fact, unleash a mechanism involving the liberation of cytochrome c that leads to neuronal apoptosis. Notably, young females appear protected against the mitochondrial toxicity of amyloid-beta, likely due to the upregulation of antioxidant enzymes which occur in females. Estrogens are responsible for this effect. Overall, the findings support the notion that amyloid-beta causes intracellular toxicity via the increased production of oxidant species. Reactive oxygen species generated by mitochondria act as a signal to start the mitochondrial apoptotic pathway. There is a possibility of prevention, and indirect evidence shows that estrogenic compounds (either endogenous estradiol or phytoestrogens such as genistein) may increase the expression of antioxidant enzymes, leading to a lowering of oxidative stress and thus protection against intracellular toxicity of amyloid-beta peptide. These ideas open up the possibility of using phytoestrogens to prevent the onset of Alzheimer's disease. More studies are required to determine whether estrogens and/or phytoestrogens fulfill these expectations.


Drinking consequences and subsequent drinking in college students over 4 years.
There is some evidence that college student drinkers may continue drinking in the face of adverse consequences. We examined 2 hypotheses: (a) that this seemingly pathological behavior is a phenomenon of university life, occurring with consistency throughout the entirety of college, and (b) that individuals accumulate these consequences over multiple semesters in college. A sample of 3,720 students from a large Midwestern university was asked to complete surveys the summer before college and every semester thereafter for 4 years. Results showed that certain drinking-related consequences (e.g., blackouts, regretted sexual experiences) consistently predicted continued frequent heavy drinking in the following semester, even after controlling for sex, race, age, and previous-semester frequent heavy drinking (range of odds ratio = 1.17 to 1.45 across semesters, p < .01). Such potent consequences may predict subsequent drinking for a number of possible reasons that may be examined and addressed as they would pertain to specific protective behavioral strategy-related and cognitive interventions. Furthermore, consequences were accumulated over multiple semesters by notable proportions of students. For example, 13.8% of students reported blacking out 5 time-points or more--describing a full half or more of their college careers. Experimental studies which aim to modify students' perceptions of norms associated with these consequences may aid in developing interventions to reduce the burden of harm to students. In the broader context, and given the prevalence of students' accumulation of consequences, future study might aim to determine how and in what ways these findings describe either pathological or normative processes.


Applications of Circulating Tumor DNA in Immune Checkpoint Inhibition: Emerging Roles and Future Perspectives.
Immune checkpoint inhibitors (ICIs), especially anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies, have made dramatic progress in the treatment of lung cancer, especially for patients with cancers not driven by oncogenes. However, responses are limited to a subset of patients, and which subset of patients will optimally benefit from ICI remains unknown. With the advantage of being minimally invasive and dynamic, noninvasive biomarkers are promising candidates to predict response, monitor resistance, and track the evolution of lung cancer during ICI treatment. In this review, we focus on the application of circulating tumor DNA (ctDNA) in plasma in immunotherapy. We examine the potential of pre- and on-treatment features of ctDNA as biomarkers, and following multiparameter analysis, we determine the potential clinical value of integrating predictive liquid biomarkers of ICIs to optimize patient management. We further discuss the role of ctDNA in monitoring treatment resistance, as well as challenges in clinical translation.


Immunophenotypical characterization of macrophages in rat bleomycin-induced scleroderma.
Scleroderma is a skin disorder characterized by persistent fibrosis. Macrophage properties influencing cutaneous fibrogenesis remain to be fully elucidated. In this rat (F344 rats) model of scleroderma, at 1, 2, 3, and 4 weeks after initiation of daily subcutaneous injections of bleomycin (BLM; 100 μl of 1 mg/ml daily), skin samples were collected for histological and immunohistochemical evaluations. Immunohistochemically, the numbers of cells reacting to ED1 (anti-CD68; phagocytic activity) and ED2 (anti-CD163; inflammatory factor production) began to increase at week 1, peaked at week 2, and decreased thereafter. In contrast, the increased number of cells reacting to OX6 (anti-MHC class II molecules) was seen from week 2 and remained elevated until week 4. α-Smooth muscle actin-positive myofibroblasts were increased for 4 weeks. Double labeling revealed that galectin-3, a regulator of fibrogenic factor TGF-β1, was expressed in CD68+, CD163+, and MHC class II+ macrophages and myofibroblasts. mRNA expression of TGF-β1, as well as MCP-1 and CSF-1 (both macrophage function modulators), were significantly elevated at weeks 1 to 4. This study shows that the increased number of macrophages with heterogeneous immunophenotypes, which might be induced by MCP-1 and CSF-1, could participate in the sclerotic lesion formation, presumably through increased fibrogenic factors such as galectin-3 and TGF-β1; the data may provide useful information to understand the pathogenesis of the human scleroderma condition.


Intracellular distribution of adenylate cyclase in human cardiocytes determined by electron microscopic cytochemistry.
Subcellular localization of adenylate cyclase (AC) in human cardiocytes was studied by electron microscopic cytochemistry using ventricular biopsies from various diseased hearts. In addition to the weak enzyme activity on the sarcolemma, the intense reaction products of AC were demonstrated within distinctive morphologic components of sarcoplasmic reticulum, nuclear envelope, and other internal membranes such as parallel lamellar structures and interlaced tubular structures in the perinuclear regions and stacked membranous structures beneath sarcolemma in cardiocytes. The distribution and intensity of cytochemical activity within different organelles was variable among biopsy cases. The reaction products of AC cytochemistry within the sarcoplasmic reticulum could be related to signal transduction targeting Ca2+ handling by the organella. Cytochemical activity within the nuclear envelope and perinuclear internal membranes possibly reflects AC participation in a signal function to regulate nuclear activity, such as gene expression. Cytochemical distribution of the enzyme in membranous structures beneath the sarcolemma is most likely related to hormone receptors and the linked activity of AC. The subcellular distribution of AC on various internal membrane structures in cardiocytes may reflect compartmentalization of the enzyme at individual intracellular sites to regulate a preferential specific signal function among multiple potential signal transductions by a cascade of AC, cyclic AMP, and cyclic AMP-dependent protein kinase. Alternatively, subcellular localization of the reaction products may reflect local enzyme synthesis or represent sites of enzyme transport, e.g., to terminal localization beneath the sarcolemma.


Evaluation of leprosy lesions by skin smear cytology in comparison to histopathology.
Cytological evaluation of leprosy skin lesion was done to evaluate cytohistological correlation. Twenty five clinically suspected patients of leprosy were evaluated by performing fine needle aspiration (FNA) in nodular lesions and slit skin smear technique in flat lesions to classify across R-J scale. May-Grunwald-Giemsa (MGG) and Ziehl-Neelsen stain were employed on slit skin smears and fine needle aspiration material. Histopathological assessment of slides from same lesion was done. The overall diagnostic accuracy of fine needle aspiration was 76.1% and that of slit skin smear 50%. However, on adequate material diagnostic accuracy of slit skin smear was high, 100% as compared to 81.8% of fine needle aspiration smears. In cases of polar leprosy cytological findings paralleled histopathological diagnosis. Within the constraints of cytological interpretation the cases in borderline unstable spectrum of leprosy can be classified broadly.


Effects of diabetes mellitus, age, and duration of dialysis on parathormone in chronic hemodialysis patients.
Secondary hyperparathyroidism (SHPTH) can develop early in the course of chronic renal failure and becomes more prominent as kidney function declines. We studied the effect of diabetes, age, and dialysis on parathyroid function in 60 (21 women, 39 males; 44 non-diabetic, 16 diabetic) hemodialysis (HD) patients. Serum intact PTH (iPTH), calcium, phosphorus, alkaline phosphatase (ALP), and magnesium (Mg) were measured. Adequacy of HD was evaluated by calculating the urea reduction rate (URR). There were significantly lower values of serum iPTH, ALP, and dialysis adequacy among diabetic than non-diabetes HD patients. In addition, there were an inverse correlation of age and serum iPTH (r= -0.27, p=0.034) as well as age and serum phosphorus (r= -0.28, p=0.031). There was also a positive correlation between serum iPTH with the duration (r=0.001, p=0.42) and doses of dialysis treatment (r=0.38, p=0.002). We conclude that a significant negative correlation between age and serum phosphorus and lower parathyroid activity in diabetic HD patients, which implies more prevalence of bone disease in elderly diabetic HD patients. Further study of bone disease in this group of patients is required to evaluate its effect on outcome and different therapeutic interventions.


HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype associated with lamotrigine-induced maculopapular exanthema in Mexican Mestizo patients.
Several HLA alleles have been associated with antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) in different populations; however, this has not been investigated in Mexican Mestizos (MM). Thus, the purpose of this preliminary study was to determine the association of HLA class I alleles with AED-induced cADRs in MM patients. This case-control association study included 21 MM patients with phenytoin (PHT)-, carbamazepine (CBZ)-, or lamotrigine (LTG)-induced maculopapular exanthema (MPE) or Stevens-Johnson syndrome (SJS); 31 MM patients tolerant to the same AEDs; and 225 unrelated, healthy MM volunteers. HLA class I genotyping was performed. Differences in HLA allele frequencies between AED-induced cADR patients and AED-tolerant patients were assessed. Frequencies of alleles possibly associated with AED-induced cADRs in MM patients were compared with those in MM population. The frequency of HLA-C*08:01 allele in PHT-induced MPE was higher than that in the PHT-tolerant group (pc=0.0179) or in the MM population (pc<0.0001). For the first time, HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype was associated with LTG-induced MPE (pc=0.0048 for LTG-tolerant groups and pc<0.0001 for MM population). Our data suggest the HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype may be a biomarker for LTG-induced MPE and the HLA-C*08:01 allele for PHT-induced MPE. We also identified HLA-A*01:01:01 and -A*31:01:02 as candidates alleles associated with CBZ-induced MPE in MM patients. However, further investigations are necessary to confirm these findings.


Synthesis and properties of peptide dendrimers containing fluorescent and branched amino acids.
In this report, we describe dendritic peptides possessing central fluorescent amino acids with adjacent branched amino acids. These fluorescent-peptide dendrimers were prepared using (9-fluorenyl)methoxycarbonyl (Fmoc)-based solid-phase peptide synthesis and Fmoc-derivative fluorescent and branched amino acids. The branched amino acids featured multiple carboxylic acids in their side chains, making the fluorescent-peptide dendrimers highly water-soluble compared with the analogous peptides containing the fluorescent amino acids only. The branched amino acid units also improved the fluorescence intensity of the dendrimers. Based on high-pressure liquid chromatography and fluorescence spectroscopy results, we determined that the fluorescent groups were located in the core and that the carboxylic acids were located on the surface of the dendrimers. Fluorescence resonance energy transfer was achieved among the three proximal fluorescent groups in one of the fabricated fluorescent-peptide dendrimers.


Dental and maxillofacial abnormalities in long-term survivors of childhood cancer: effects of treatment with chemotherapy and radiation to the head and neck.
Sixty-eight long-term survivors of childhood cancer were evaluated for dental and maxillofacial abnormalities. Forty-five patients had received maxillofacial radiation for lymphoma, leukemia, rhabdomyosarcoma, and miscellaneous tumors. Forty-three of the 45 patients and the remaining 23 who had not received maxillofacial radiation also received chemotherapy. Dental and maxillofacial abnormalities were detected in 37 of the 45 (82%) radiated patients. Dental abnormalities comprised foreshortening and blunting of roots, incomplete calcification, premature closure of apices, delayed or arrested tooth development, and caries. Maxillofacial abnormalities comprised trismus, abnormal occlusal relationships, and facial deformities. The abnormalities were more severe in those patients who received radiation at an earlier age and at higher dosages. Possible chemotherapeutic effects in five of 23 patients who received treatment for tumors located outside the head and neck region comprised acquired amelogenesis imperfecta, microdontia of bicuspid teeth, and a tendency toward thinning of roots with an enlarged pulp chamber. Dental and maxillofacial abnormalities should be recognized as a major consequence of maxillofacial radiation in long-term survivors of childhood cancer, and attempts to minimize or eliminate such sequelae should involve an effective interaction between radiation therapists, and medical and dental oncologists.


Comparison of binding sites in DNA for berenil, netropsin and distamycin. A footprinting study.
Techniques of DNase I and micrococcal nuclease footprinting have been used to compare the binding sites for berenil, netropsin and distamycin on two different DNA fragments. Each ligand binds to the A + T-rich zones which contain clusters of at least four A.T base pairs. Neither guanosine nor cytidine nucleotides appear to be allowed within the A + T-rich runs which constitute the preferred binding sites, although they are sometimes protected from DNase I cleavage in neighbouring regions. Berenil and netropsin share with distamycin the property of causing enhanced rates of cleavage at certain sequences flanking their binding sites. There are significant differences in the concentrations of each ligand required to produce defined patterns of protection, seemingly dependent upon the nature (and possibly the gross base composition) of the piece of DNA being used in the experiment.


Kinetic-based trapping by intervening sequence variants of the active sites of protein-disulfide isomerase identifies platelet protein substrates.
Thiol isomerases such as protein-disulfide isomerase (PDI) direct disulfide rearrangements required for proper folding of nascent proteins synthesized in the endoplasmic reticulum. Identifying PDI substrates is challenging because PDI catalyzes conformational changes that cannot be easily monitored (e.g. compared with proteolytic cleavage or amino acid phosphorylation); PDI has multiple substrates; and it can catalyze either oxidation, reduction, or isomerization of substrates. Kinetic-based substrate trapping wherein the active site motif CGHC is modified to CGHA to stabilize a PDI-substrate intermediate is effective in identifying some substrates. A limitation of this approach, however, is that it captures only substrates that are reduced by PDI, whereas many substrates are oxidized by PDI. By manipulating the highly conserved -GH- residues in the CGHC active site of PDI, we created PDI variants with a slowed reaction rate toward substrates. The prolonged intermediate state allowed us to identify protein substrates that have biased affinities for either oxidation or reduction by PDI. Because extracellular PDI is critical for thrombus formation but its extracellular substrates are not known, we evaluated the ability of these bidirectional trapping PDI variants to trap proteins released from platelets and on the platelet surface. Trapped proteins were identified by mass spectroscopy. Of the trapped substrate proteins identified by mass spectroscopy, five proteins, cathepsin G, glutaredoxin-1, thioredoxin, GP1b, and fibrinogen, showed a bias for oxidation, whereas annexin V, heparanase, ERp57, kallekrein-14, serpin B6, tetranectin, and collagen VI showed a bias for reduction. These bidirectional trapping variants will enable more comprehensive identification of thiol isomerase substrates and better elucidation of their cellular functions.


Bizarre presentation of epigastric heteropagus: report of a case.
We report an unusual case of epigastric heteropagus in a female neonate. The parasite had a single lung as well as a liver, stomach, intestine, pancreas, ovaries, a single kidney, and a bladder. These visceral organs were located in the abdominal and pelvic space of the autosite, and the pelvic bone and lower legs of the parasite were fused with the respective organs in the autosite. The infant underwent operations to remove the central leg and some of the intra-abdominal organs of the parasite, but she must still undergo further surgery to remove the genitourinary organs and pelvic bones of the parasite, and repair her very abducted and rotated right leg.


[The clinical administration of the opioid antagonist naloxone in dogs].
The short introduction gives a review on the complex of exogen and endogen opioids and their receptors as well as on their pharmacodynamics, pharmacokinetics and toxicity of naloxone. The clinical efficacy of naloxone as an opioid antagonist is described. Applications of naloxone for the dog are specified: antagonisation of etorphine, morphine, levomethadone and fentanyl, antagonisation of exogen and endogen opioids in puppies and treatment of lactomania in the bitch. The mean effective dose to antagonize morphines is 0.003 mg/kg bodyweight. If persisting analgesia is indicated the dose of naloxone in titrating steps in 0.001 mg/kg bw. To antagonize postpartal hypoxia in puppies 0.02 mg per animal naloxone have to be injected. For treatment of lactomania a dose of 0.01 mg/kg bodyweight twice a day for a couple of days is recommended. The clinical effectivity of naloxone is proved doubtlessly. Compatibility and safety are very high.


Parasites of wild felidae in Thailand: a coprological survey.
Ninety-two fecal samples were collected from leopards (Panthera pardus, n = 54), tigers (P. tigris, n = 19), and leopard cats (Felis bengalensis, n = 3) in Huai Kha Wildlife Sanctuary, Thailand; four samples that may have come from clouded leopards (Neofelis nebulosa) or Asian golden cats (Felis temminicki) were identified as from small to medium cats. Twelve samples were identified as from large cats. Samples preserved in 10% formalin were examined for parasite eggs, larvae, cysts, and oocysts by centrifugal sugar flotation and sedimentation techniques. Ninety-six percent of all samples were positive, including 94% of the leopard, all of the tiger, clouded leopard, golden cat, and leopard cat samples. Diagnostic stages were identified from Paragonimus sp., Echinostomatidae, Dicrocoeliidae, Pseudophyllidea, Taeniidae, Mesocestoides sp., Hymenolepididae, Acanthocephala, Spiruroidea, Gnathostoma sp., Molineus sp., Ancylostomoidea, Mammomonogamus sp., Toxocara sp., Toxascaris sp., Metastrongyloidea, Capillaria spp., Isospora sp., Toxoplasma-like, Sarcocystis spp., and Giardia sp.


Reductions in the number of mid-sized antral follicles are associated with markers of premature ovarian senescence in dairy cows.
High-producing dairy cows are subfertile; however, the mechanisms responsible for the decreased fertility are unknown. The aim of the present study was to test the hypothesis that culled dairy cows (4-8 years old) characterised by 'Lo' ovaries (i.e. those with <10 mid-antral follicles) are affected by premature ovarian senescence. Cows in which both ovaries were 'Lo' ovaries represented 5% of the total population analysed, and exhibited reduced ovarian size (P<0.001) and increased perifollicular stroma (P<0.05) compared with age-matched controls (i.e. cows in which both ovaries had >10 mid-antral follicles; 'Hi' ovaries). The total number of follicles, including healthy and atretic primordial, primary, secondary and small antral follicles, was lower in Lo ovaries (P<0.01). Interestingly, the primordial follicle population in Lo ovaries was lower (P<0.05) than in the control. Finally, the follicular fluid of mid-antral follicles from Lo ovaries had reduced oestradiol and anti-Müllerian hormone levels (P<0.05), but increased progesterone concentrations (P<0.05). Together, these data account for the reduced fertility of cows with Lo ovaries and are in agreement with previous observations that oocytes isolated from Lo ovaries have reduced embryonic developmental competence. Cows with a specific Lo ovary condition may represent a suitable model to address the causes of low fertility in high-yielding dairy cows, as well as the condition of premature ovarian aging in single-ovulating species.


A microfluidic chamber-based approach to map the shear moduli of vascular cells and other soft materials.
There is growing interest in quantifying vascular cell and tissue stiffness. Most measurement approaches, however, are incapable of assessing stiffness in the presence of physiological flows. We developed a microfluidic approach which allows measurement of shear modulus (G) during flow. The design included a chamber with glass windows allowing imaging with upright or inverted microscopes. Flow was controlled gravitationally to push culture media through the chamber. Fluorescent beads were conjugated to the sample surface and imaged before and during flow. Bead displacements were calculated from images and G was computed as the ratio of imposed shear stress to measured shear strain. Fluid-structure simulations showed that shear stress on the surface did not depend on sample stiffness. Our approach was verified by measuring the moduli of polyacrylamide gels of known stiffness. In human pulmonary microvascular endothelial cells, G was 20.4 ± 12 Pa and decreased by 20% and 22% with increasing shear stress and inhibition of non-muscle myosin II motors, respectively. The G showed a larger intra- than inter-cellular variability and it was mostly determined by the cytosol. Our shear modulus microscopy can thus map the spatial distribution of G of soft materials including gels, cells and tissues while allowing the visualization of microscopic structures such as the cytoskeleleton.


[Streptomycin was born fifty years ago].
The discovery of streptomycin by Waksman in 1943 marked the beginning of true chemotherapy in all forms of tuberculosis. The possibility to reverse the lethal course of tuberculous meningitis in children constituted a hope verged on enthusiasm. But after encouraged results, skepticism arose: cases of resistance of BK to streptomycin were reported and other observations noted severe sequelae when administration had begun too late. Successes due to drug were often weakened by side effects like cochlear and vestibular deficiencies. All those reservations came in addition to the great price of streptomycin, difficulties of its supply and doubts upon long term prognosis for cared patients. Finally streptomycin won. In the following years, new drugs more and more efficient against tuberculosis were used, instead of streptomycin which some enthusiastic people had nevertheless thought only able to eradicate the "white plague". Today, morbidity and mortality from tuberculosis remain dramatic, partly accelerated by the AIDS epidemic and increased by high frequency of cases with BK resistance to all drugs ... except streptomycin. What a long story, full of hopes, for this antibiotic which, during the first clinical trials, saved from certain death ... a child became the author of the present paper!


Hemoperfusion as an effective alternative therapy for star fruit intoxication: a report of 2 cases.
This report describes 2 cases of star fruit intoxication successfully treated with charcoal hemoperfusion (CHP). Common clinical characteristics of the reported cases included persistent hiccup, consciousness disturbance, coma, need for ventilator support, and admission to an intensive care unit. The optimum treatment for star fruit intoxication has been controversial, with modality, dose, and appropriate timing of extracorporeal therapy debated. Analysis of the 2 reported cases shows several advantages of CHP, including increased extraction efficiency, rapid recovery of consciousness, decreased time of intensive care unit admission, and good clinical tolerance. CHP may provide an alternative treatment modality in cases with life-threatening star fruit intoxication with poor response to intensified hemodialysis.


Integration of Attitude, Ethics, and Communication Competencies into Competency-based UG Curriculum.
The new MBBS curriculum has a course called Attitudes, Ethics, and Communication (AETCOM) which will run across years. Students will be assessed for how they communicate with patients, how they counsel people for organ donation or other challenging procedures, how sensitively they offer care and obtain informed consent? All these elements will count along with competencies. The new regulations mandate the development of AETCOM competencies through 27 modules with emphasis on self-directed learning. Ultimately it is expected that these modules are integrated into the basic curriculum of Indian Medical Graduates. Each module is a comprehensive self-contained unit. It describes learning objectives of competencies addressed, level of learning, contents of learning, professional year of study, hours of study, methods of learning and their formative and summative assessment along with accessible resource material.


Epitope Mapping of an Anti-Human Epidermal Growth Factor Receptor Monoclonal Antibody (EMab-51) Using the RIEDL Insertion for Epitope Mapping Method.
The classic method for identifying the epitope that monoclonal antibodies (mAbs) bind uses deletion mutants and point mutants of the target protein. However, determining the epitope of mAbs-reactive membrane proteins is often challenging. We recently developed the RIEDL insertion for epitope mapping (REMAP) method to identify mAb-binding epitopes. Herein, we first checked the reactivity of an anti-epidermal growth factor receptor (EGFR) mAb (EMab-51) to several EGFR deletion mutants such as EGFR/dN152, EGFR/dN313, EGFR/dN370, EGFR/dN375, EGFR/dN380, and EGFR/dN482. We found the N-terminus of the EMab-51-binding epitope between residues 375 and 380 of EGFR. We next produced EGFR/dN313 mutants with the RIEDL peptide tag inserted at each possible position of 375-AFRGDSFTHTPPLDP-389. EMab-51 lost its reactivity with the mutants having a RIEDL tag inserted at each position of 377-RGDSFTHTPP-386, whereas LpMab-7 (an anti-RIEDL mAb) detected every mutant. Thus, using the REMAP method, we identified the EMab-51-binding epitope of EGFR as 377-RGDSFTHTPP-386.


Oral peanut challenge identifies an allergy but the peanut allergen threshold sensitivity is not reproducible.
Double-blind placebo-controlled food challenge, DBPCFC, the gold standard for diagnosing food allergy, is time-consuming and potentially dangerous. A basophil allergen threshold sensitivity test, CD-sens, has shown promising results as a diagnostic tool in food allergy. To evaluate the reproducibility of oral peanut challenge and compare the outcome to CD-sens in peanut-sensitized children. Twenty-seven children (4-19 years) underwent a DBPCFC followed by a single-blind oral food-challenge. The peanut challenges (1 mg to 5 g) were evaluated by severity scoring. Blood samples were drawn for CD-sens before the two first challenges. Thirteen children (48%) did not react at any of the challenges. Fourteen reacted at both peanut challenges but not to placebo. Only two of these children reacted at the same threshold dose and with the same severity score. All other children scored differently or reacted at different doses. For children with a positive challenge the geometric mean of the ratio of the doses was 1.834 (p = 0.307) and the arithmetic mean of the difference between the severity scores was 0.143 (p = 0.952). No association was obtained between the two peanut challenges regarding severity score (r(s) = 0.11, p = 0.71) or threshold dose (r(s) = 0.35, p = 0.22). Among the children positive in peanut challenge, 12 were positive in CD-sens. Two were low-responders and could not be evaluated. Geometric mean of the ratio of CD-sens values in children with a positive challenge was 1.035 (p = 0.505) but unlike for the severity score and the threshold dose the association between the two CD-sens values was strong (r(s) = 0.94, P<0.001). For a positive/negative test the reproducibility is 100% for both peanut challenge and CD-sens. However, a comparison of the degree of allergen threshold sensitivity between the two tests is not possible since the threshold dose and severity scoring is not reproducible.


Paving the way. Outcome planner for the orthopaedic patient at home.
The home care nurse often spent more time documenting than actually caring for the patient. The decision was made to streamline documentation, and our road to outcome planners began.


Effects of Porosity on Piezoelectric Characteristics of Polyvinylidene Fluoride Films for Biomedical Applications.
Objective: The objective of this work is to study the effects of porosity on mechanical and piezoelectric properties of polyvinylidene fluoride (PVDF) films for biomedical applications. Impact Statement: By investigating the piezoelectric properties of PVDF and the porosity effect on its electromechanical performance, there is potential for further development of PVDF as a hemodynamic sensor that can lead to further technological advancements in the biomedical field, benefiting patients and physicians alike. Introduction: PVDF thin films have shown potential in the application of hemodynamic flow sensing and monitoring the effects on blood flow caused by prosthetic valve implantation via the transcatheter aortic valve replacement operation. The piezoelectric performance of PVDF films can be influenced by the porosity of the material. Methods: In this study, strain tracking was performed on thin film PVDF specimens with various levels of porosity and pore sizes to determine the mechanical properties of the specimens. The mechanical properties were used to model the PVDF material in COMSOL multiphysics software, in which compression test simulations were performed to determine the piezoelectric coefficient d33 of the PVDF. Results: A decline in the elastic modulus was found to be highly inversely correlated with porosity of the specimens and the simulation results show that elastic modulus had a much greater effect on the piezoelectric properties than Poisson's ratio. Conclusion: A combination of experimental and computational techniques was able to characterize and correlate the mechanical properties of PVDF films of varying porosities to their piezoelectric properties.


German-Canadian family (family A) with parkinsonism, amyotrophy, and dementia - Longitudinal observations.
Etiology of Parkinson's disease (PD), amyotrophy lateral sclerosis (ALS), and Alzheimer's disease (AD) remains uncertain. Environmental factors probably play a role, but genetic influences may predispose certain individuals to develop each of these major neurodegenerative disorders. We describe our longitudinal observations concerning a Canadian family traced to Northern Germany. Autosornal dominant inheritance has been established. Affected members present with L-dopa responsive parkinsonism and amyotrophy. In the German portion of the family some individuals displayed only dementia or focal dystonia. Linkage analysis studies performed with polymorphic markers associated with 13 candidate genes provided no significant evidence for linkage with any of the genes examined. Positron emission tomography with [(18)F]-6-fluoro-L-dopa (FD) and [su11C]-raclopride (raclopride) of one affected subject revealed reduced striatal FD uptake particularly in putamen, and an increased raclopride striatum/background ratio. Postmortem levels of dopamine and its metabolites were greatly reduced in caudate and putamen of two patients. There was substantial neuronal loss in the substantia nigra and the presence of abundant eosinophilic granules (different than Lewy bodies) in surviving neurons. One of them also showed mild loss of anterior horn cells, while another showed abundant senile plaques and some neurofibrillary tangles in distribution and intensity typical of mild to moderate AD. Our report further describes this unique family with a combination of clinical features of PD, ALS, and AD. By studying kindreds like this we may learn more about the pathophysiology of sporadic forms of PD, ALS, or even AD.


Enhancement in the histological diagnosis of leprosy in patients with only sensory loss by demonstration of mycobacterial antigens using anti-BCG polyclonal antibodies.
This study was undertaken to assess whether the immunoperoxidase technique using anti-BCG serum is able to confirm the diagnosis of early leprosy among patients whose unique clinical manifestation is a localized area of sensory loss, in a higher proportion than the routine mycobacterial staining methods, namely hematoxylin-eosin and Wade. The study was held in the north of a hyper-endemic area of leprosy, Manaus, Amazonas (Brazil). Fifty-one paraffin-embedded skin biopsy blocks were retrieved and processed for the immunohistochemical study, by means of anti-BCG polyclonal antibodies for the detection of mycobacterial antigens. The routine stains confirmed the leprosy diagnosis in 17% of the cases, while the immunostaining method confirmed it in 47%. The McNemar test showed that the observed difference between these two techniques was statistically significant (p = < 0.05). In the same way, 50 blocks of skin conditions considered in the differential histopathological diagnosis of early leprosy were processed for the immunohistochemical test to analyze the possibility of false-positive results which occurred in 8 (16%) patients. The study suggests that immunostaining may increase the proportion of the routine histological diagnosis of leprosy in patients who have sensory loss only, even while using biopsies obtained in fieldwork conditions. This is very advantageous in hyper-endemic areas and in areas that are in the post-elimination period of leprosy control where sensory loss may be a sentinel sign of the disease.


[Comparison of 4 technics for collecting bacteria on cement, asbestos-cement and steel in hen-breeding buildings].
A comparative study between 4 sampling techniques (swabbing, pistol-washing, printing on agar medium either with or without neutralizer) was performed on three materials (concrete, asbestos-concrete, steel) following numeration of three bacterial flora (the total aerobic flora, faecal streptococci, pseudomonas). The highest levels of contamination were detected with pistol-washing irrespective of the substrate and flora recovered. A correlative study carried out from the contamination levels reveals that a significant correlation exists in all cases, with a low probability of error.


The demise of a planned randomised controlled trial in an urban Aboriginal medical service.
To fill a gap in knowledge about the effectiveness of brief intervention for hazardous alcohol use among Indigenous Australians, we attempted to implement a randomised controlled trial in an urban Aboriginal Medical Service (AMS) as a joint AMS-university partnership. Because of low numbers of potential participants being screened, the RCT was abandoned in favour of a two-part "demonstration project". Only 16 clients were recruited for follow-up in six-months, and the trial was terminated. Clinic, patient, Aboriginal health worker, and GP factors, interacting with study design factors, all contributed to our inability to implement the trial as designed. The key points to emerge from the study are that alcohol misuse is a difficult issue to manage in an Indigenous primary health care setting; RCTs involving inevitably complex study protocols may not be acceptable or sufficiently adaptable to make them viable in busy, Indigenous primary health care settings; and "gold-standard" RCT-derived evidence for the effectiveness of many public health interventions in Indigenous primary health care settings may never be available, and decisions about appropriate interventions will often have to be based on qualitative assessment of appropriateness and evidence from other populations and other settings.


Study of compounds suppressing free radical generation from UV-exposed ketoprofen.
Ketoprofen [(RS)-2-(3-benzoylphenyl)propanoic acid] is widely used for the treatment of inflammatory diseases and musculoskeletal injury. However, there is concern regarding its potential for photosensitization as a side effect. Free radicals and active oxygen species generated from ketoprofen on exposure to ultraviolet (UV) light have been implicated in phototoxicity and photosensitization. In this study, we examined the suppressing ability of some compounds for the free radicals and active oxygen species generated by the photodynamic reaction of ketoprofen, to determine a new resist of photosensitization by ketoprofen. Eight compounds, including six known free radical scavengers were individually mixed with ketoprofen, and the mixtures were exposed to UV. Then, the free radicals and the active oxygen species were determined by the electron spin resonance spectrometry to estimate suppressing and scavenging ability of compounds. The compounds that show promise in suppressing superoxide anion generation from UV-exposed ketoprofen were further evaluated using the on-line photo-irradiated superoxide anion detection system. It was confirmed that quercetin, a flavonoid, strongly suppresses the generation of free radicals and active oxygen species from UV-exposed ketoprofen. The experiments using the experimental formulation of an adhesive skin patch of ketoprofen containing quercetine and the Chemiluminescence analyzer (CLA) indicated that quercetin has high potential for use as an excipient in ketoprofen ointments to suppress phototoxicity and photosensitization by ketoprofen.


Preclinical diabetes mellitus in precocious myocardial infarction.
A series of 45 patients who had a myocardial infarction before the age of 45 years has been studied and investigated for alterations of glucose tolerance, as shown by standard and prednisolone-primed glucose tolerance tests. Abnormal responses to standard glucose tolerance tests and prednisolone-primed glucose tolerance tests were obtained in 75.5 per cent of patients with myocardial infarction, compared with 8.8 per cent of controls.Sex, hypertension, obesity, and a positive family history did not affect the abnormalities of glucose tolerance. Various views concerning these abnormalities in glucose metabolism are discussed.


Pedicle screw insertion: robotic assistance versus conventional C-arm fluoroscopy.
Bone-mounted robotic guidance for pedicle screw placement has been recently introduced, aiming at increasing accuracy. The aim of this prospective study was to compare this novel approach with the conventional fluoroscopy assisted freehand technique (not the two- or three-dimensional fluoroscopy-based navigation). Two groups were compared: 11 patients, constituting the robotical group, were instrumented with 64 pedicle screws; 23 other patients, constituting the fluoroscopic group, were also instrumented with 64 pedicle screws. Screw position was assessed by two independent observers on postoperative CT-scans using the Rampersaud A to D classification. No neurological complications were noted. Grade A (totally within pedicle margins) accounted for 79% of the screws in the robotically assisted and for 83% of the screws in the fluoroscopic group respectively (p = 0.8). Grade C and D screws, considered as misplacements, accounted for 4.7% of all robotically inserted screws and 7.8% of the fluoroscopically inserted screws (p = 0.71). The current study did not allow to state that robotically assisted screw placement supersedes the conventional fluoroscopy assisted technique, although the literature is more optimistic about the former.


Shrinking the hammer: micromechanical approaches to morphogenesis.
Morphogenesis, the remarkable process by which a developing organism achieves its shape, relies on the coordinated growth of cells, tissues, and organs. While the molecular and genetic basis of morphogenesis is starting to be unravelled, understanding shape changes is lagging behind. Actually, shape is imposed by the structural elements of the organism, and the translation of cellular activity into morphogenesis must go through these elements. Therefore, many methods have been developed recently to quantify, at cellular resolution, the properties of the main structural element in plants, the cell wall. As plant cell growth is restrained by the cell wall and powered by turgor pressure, such methods also address the quantification of turgor. These different micromechanical approaches are reviewed here, with a critical assessment of their strengths and weaknesses, and a discussion of how they can help us understand the regulation of growth and morphogenesis.


Chained Iron Microparticles for Directionally Controlled Actuation of Soft Robots.
Magnetic field-directed self-assembly of magnetic particles in chains is useful for developing directionally responsive materials for applications in soft robotics. Using materials with greater complexity allows advanced functions, while still using simple device architectures. Elastomer films containing chained magnetic microparticles were prepared through solvent casting and formed into magnetically actuated lifters, accordions, valves, and pumps. Chaining both enhances actuation and imparts a directional response. Cantilevers used as lifters were able to lift up to 50 times the mass of the polymer film. We introduce the "specific torque", the torque per field per mass of magnetic particles, as a figure of merit for assessing and comparing the performance of lifters and related devices. Devices in this work generated specific torques of 68 Nm/kgT, which is significantly higher than in previously reported actuators. Applying magnetic fields to folded accordion structures caused extension and compression, depending on the accordion's orientation. In peristaltic pumps comprised of composite tubes containing embedded chains, magnetic fields caused a section of the tube to pinch closed where the field was applied. These results will facilitate both the further development of soft robots based on chained magnetic particles and efforts to engineer materials with higher specific torque.


Instrumentation of a gravity feed extruder and the influence of the composition of binary and ternary mixtures on the extrusion forces.
A gravity feed extruder was adapted to monitor the extrusion forces, the temperature during processing and the rotational speed of the extruding cylinders. The extruder was used to evaluate the influence of particle size of insoluble material and of product solubility on the extrusion forces. Microcrystalline cellulose, dicalcium phosphate dihydrate and different lactoses were used as model compounds. Difference in lactose and microcrystalline cellulose particle size did not influence extrusion forces. The amount of water in the mixtures to be processed and the initial difference in solubility for some of the lactose types investigated influenced the extrusion forces dramatically. Extrusion forces recorded during processing of a mixture previously granulated in a high shear granulator were higher than when processed in a planetary mixture. Loss of water during high shear granulation is probably the main cause of this phenomenon.


Mechanisms of protein misfolding in conformational lung diseases.
Genetic or environmentally-induced alterations in protein structure interfere with the correct folding, assembly and trafficking of proteins. In the lung the expression of misfolded proteins can induce a variety of pathogenetic effects. Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two major clinically relevant pulmonary disorders associated with protein misfolding. Both are genetic diseases the primary causes of which are expression of mutant alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) and SERPINA1, respectively. The most common and best studied mutant forms of CFTR and AAT are ΔF508 CFTR and the Glu342Lys mutant of AAT called ZAAT, respectively. Non-genetic mechanisms can also damage protein structure and induce protein misfolding in the lung. Cigarette-smoke contains oxidants and other factors that can modify a protein's structure, and is one of the most significant environmental causes of protein damage within the lung. Herein we describe the mechanisms controlling the folding of wild type and mutant versions of CFTR and AAT proteins, and explore the consequences of cigarette-smoke-induced effects on the protein folding machinery in the lung.


Reporting of adverse events in hospitals in Victoria, 1994-1995.
To describe the nature and frequency of adverse events (AEs) reported in routine inpatient data collection. Retrospective analysis of data from the Victorian Inpatient Minimum Database. All public (135) and private (112) acute-care hospitals in Victoria, 1994-1995. All patients with separations recording an E-code identified as an AE through the International classification of diseases, ninth revision (ICD-9), classification system. Australian national diagnosis-related groups (AN-DRGs) associated with AEs; prevalence of major organ system disease in each of the AE groups; AE rates by hospital type; and impact of AEs on discharge destination, or death. AEs were recorded in 5% of separations, with incidence increasing with patient age. Most (81%) were complications after surgery or other procedures (E878-E879); 19% were adverse drug effects (E930-E949) and 1.7% were misadventures (E870-E876). The most frequently reported complications were infections, haemorrhage and pneumonia. AN-DRGs--joint replacement of the lower limb, bowel excision and hysterectomy--contributed most to the volume of AEs, while the greatest risk was associated with ventricular shunt, major organ transplantation and surgery for complicated injuries. The in-hospital death rate in patients with AEs was 2.9% (95% confidence interval [95% CI], 2.7%-3.2%), compared with 1.3% (95% CI, 1.0-1.4) in those without an AE. Of patients with an AE, fewer were discharged directly home, and higher proportions were discharged to other acute-care facilities or nursing homes compared with those without an AE. Inpatient data collection can provide information about AE rates associated with individual procedures, and the nature of these AEs. It can be used by hospitals to direct and complement their own quality improvement activities. Its limitation is that it cannot identify the severity or long term outcome of AEs.


The impact of bilateral salpingo-oophorectomy on sexuality and quality of life in women with breast cancer.
To compare sexual function and quality of life (QoL) in breast cancer survivors with and without a history of bilateral salpingo-oophorectomy (BSO). A cross-sectional study of breast cancer survivors treated at a tertiary referral hospital in Western Australia. The Female Sexual Function Index was used to determine rates of female sexual dysfunction (FSD) and hypoactive sexual desire disorder (HSDD). Participants also completed the Relationship Assessment Scale, Menopause-specific quality of life questionnaire and Short Form Health Survey-36. A total of 427 women were invited to participate: 119 had undergone BSO and 308 were controls with at least one ovary remaining. A total of 172 women participated (overall response rate 40.3%), consisting of 76 women in the BSO group (response rate 63.9%) and 96 women with at least one ovary remaining (response rate 31.2%). There was no difference in FSD between the two groups: 63/76 (82.9%) women who had undergone BSO had FSD compared to 75/96 (78.1%) controls (p = 0.458). No difference in HSDD was observed (p = 0.084) between the BSO group 70/76 (96.0%) and the controls 96/96 (100%). Women who had undergone BSO had lower general health scores compared to the control group (p = 0.034). Both groups had similar energy levels, emotional well-being, pain scores, physical functioning levels and social functioning levels. In this study, women with prior treatment for breast cancer had high levels of FSD and HSDD, irrespective of whether they had undergone BSO. Both groups reported similar sexual function scores and QoL.


Bone Mineral Density in Survivors of Childhood Acute Lymphoblastic Leukemia
Background: The objective of this study was to evaluate bone mineral density (BMD) after completion of treatment for childhood acute lymphoblastic leukemia (ALL). Methods: In this cross-sectional study, 103 survivors of ALL aged 13.5 ± 0.45 who completed their treatment at least one year earlier were enrolled. Among these, 49.5% and 51.5% received chemotherapy alone and chemotherapy plus cranial radiotherapy, respectively. Bone mineral content, BMD, and bone mineral apparent density in the lumbar spine (LS), femoral neck (FN) and forearm were assessed using dual-energy X-ray absorptiometry (DEXA). BMD Z-scores were classified according to International Society for Clinical Densitometry (ISCD) criteria. Results: The mean BMD Z-scores ± SD forLS, FN and forearm were -1.60 ± 0.12, -1.21 ± 0.9 and -2.43 ± 0.14 respectively with significant differences (P<0.001). Considering the lowest BMD Z-score in LS and FN areas (at any site) and according to the ISCD classification, 62.1%, 33% and 4.9% of the patients had normal BMD, low BMD and osteoporosis, respectively. Also, 8.7% of patients had developed fractures after completion of the treatment period, 4.9% having BMD Z-Scores <-2 SD at any site. A direct relationship was apparent between BMD Z-scores at LS and FN at any sites and risk of fracture (P<0.001). Conclusions: ALL patients are at risk for low BMD and fracture. Therefore, applying DEXA scanning is recommended after completion of therapy for prevention of BMD reduction and osteoporosis.


A novel cycloartane triterpenoid from Cimicifuga induces apoptotic and autophagic cell death in human colon cancer HT-29 cells.
The extract from Cimicifuga, a genus of flowering plants, has been demonstrated to have mainly therapeutic effects on menstrual and menopausal symptoms and also exhibits immunomodulatory, anti-inflammatory and antimicrobial activity. Moreover, the anticancer effects of Cimicifuga have been reported, but the underlying mechanism causing cancer cell death has been poorly described. The present study was designed to investigate the antitumor effects and underlying molecular mechanisms of cimigenol (KY17), a novel cycloartane triterpenoid from Cimicifuga. KY17-induced autophagy and apoptotic cell death in human colon cancer cells (HT-29) was investigated. KY17 treatment induced growth inhibition and apoptotic cell death in a concentration-dependent manner. The induction of apoptosis was confirmed by a change in cell morphology, and an increase in the G2/M phase, as well as increased protein levels of cleaved-caspase-8 and -3; cleavage of poly(ADP-ribose) polymerase (PARP) in the HT-29 cells following KY17 treatment. In addition, autophagy was evaluated by the accumulation of acridine orange, the appearance of green fluorescent protein-light-chain 3 (LC3) punctate structures and increased levels of LC3-II protein expression. Furthermore, combination treatment with the autophagy inhibitor bafilomycin A1 enhanced the induction of apoptosis by KY17. Taken together, the present study provides new insight into the role of KY17 as a potential antitumor compound. Combination of KY17 with an autophagy inhibitor may be a valuable strategy for the chemoprevention or treatment of colon cancer.


Effect of some flavonic compounds and ascorbic acid on lactoferrin stimulation of erythrocyte glycolysis and Na+/ K+-atpase activity.
The aim of the present study was to assess if some flavonic compounds (quercetin, piceatannol and apigenin) and ascorbic acid could interfere with the Lf stimulatory effect on the erythrocyte function. Quercetin (1.5 microM) and piceatannol (30 microM) showed an additive effect on Lf stimulation of Na+/ K+-ATPase when used together with Lf. The enhancement of Lf stimulation on Na+/ K+-ATPase in the presence of flavonoids was probably due to their antioxidative properties and/or to their involvement in the erythrocyte signaling. None of the estimated flavonoids showed an effect on Lf stimulation of the lactate production. Quercetin itself enhanced the ATPase activity but did not affect the lactate formation. Apigenin (1.5 microM) enhanced reliably the lactate generation, but it did not exert any effect on the ATPase activity. High concentration of ascorbic acid (60 mM) did not change the Lf stimulatory effect on Na+/ K+-ATPase, but decreased the Lf-specific-binding. A significantly strong inhibitory effect on the Lf-specific binding exerted the electron acceptors NAD+ (2 mM) and FAD (2 mM). These effects concern most likely the competition with Lf for electron(s) which is (are) provided from the erythrocyte intercellular electron transport chain(s).


Specificity in cholesterol regulation of gene expression by coevolution of sterol regulatory DNA element and its binding protein.
When demand for cholesterol rises in mammalian cells, the sterol regulatory element (SRE) binding proteins (SREBPs) are released from their membrane anchor through proteolysis. Then, the N-terminal region enters the nucleus and activates genes of cholesterol uptake and biosynthesis. Basic helix-loop-helix (bHLH) proteins such as SREBPs bind to a palindromic DNA sequence called the E-box (5'-CANNTG-3'). However, SREBPs are special because they also bind direct repeat elements called SREs. Importantly, sterol regulation of all promoters studied thus far is mediated by SREBP binding only to SREs. To study the reason for this we converted the direct repeat SRE from the sterol-regulated low-density lipoprotein receptor promoter into an E-box. In this report we show that SREBPs are still able to bind and activate this promoter however, sterol regulation is lost. The results are consistent with the mutant promoter being a target for promiscuous activation by constitutively expressed E-box binding bHLH proteins that are not regulated by cholesterol. Kim and coworkers [Kim, J. B., Spotts, G. D., Halvorsen, Y.-D., Shih, H.-M., Ellenberger, T., Towle, H. C. & Spiegelman, B. M. (1995) Mol. Cell. Biol. 15, 2582-2588] demonstrated that the dual DNA binding specificity of SREBPs is caused by a specific tyrosine in the conserved basic region of the DNA binding domain that corresponds to an arginine in all other bHLH proteins that recognize only E-boxes. Taken together the data suggest an evolutionary mechanism where a DNA binding protein along with its recognition site have coevolved to ensure maximal specificity and sensitivity in a crucial nutritional regulatory response.


Importance of a midterm time horizon for addressing ethical issues integral to nanobiotechnology.
There is a consensus emerging on the importance of upstream ethical engagement in nanobiotechnology. Such a preventive ethic would anticipate downstream concerns that might arise and mitigate them as part of the research and development process. However, there is an unappreciated tension between the time horizon of upstream ethics and that assumed by most bioethical research. Current standards of high-quality research on ethical issues biases the research in favor of near-term, science-based, results-oriented work. A near-term focus would miss many of the important ethical issues integral to nanobiotechnology and undermine the goals integral to upstream ethical engagement. However, if we move to a far-term time horizon, the ethical debates tend to get too speculative and are no longer disciplined by existing research trajectories. This paper addresses the link between the midterm time horizon necessary for upstream ethics and the form, content, and style of ethical reflection. New paradigm cases, standards, and criteria will be needed for high-quality upstream ethics work in the area of nanobiotechnology.


Increase in Efficacy of Checkpoint Inhibition by Cytokine-Induced-Killer Cells as a Combination Immunotherapy for Renal Cancer.
Cytokine-induced killer (CIK) cells are heterogeneous, major histocompatibility complex (MHC)-unrestricted T lymphocytes that have acquired the expression of several natural killer (NK) cell surface markers following the addition of interferon gamma (IFN-γ), OKT3 and interleukin-2 (IL-2). Treatment with CIK cells demonstrates a practical approach in cancer immunotherapy with limited, if any, graft versus host disease (GvHD) toxicity. CIK cells have been proposed and tested in many clinical trials in cancer patients by autologous, allogeneic or haploidentical administration. The possibility of combining them with specific monoclonal antibodies nivolumab and ipilimumab will further expand the possibility of their clinical utilization. Initially, phenotypic analysis was performed to explore CD3, CD4, CD56, PD-1 and CTLA-4 expression on CIK cells and PD-L1/PD-L2 expression on tumor cells. We further treated CIK cells with nivolumab and ipilimumab and measured the cytotoxicity of CIK cells cocultured to renal carcinoma cell lines, A-498 and Caki-2. We observed a significant decrease in viability of renal cell lines after treating with CIK cells (p < 0.0001) in comparison to untreated renal cell lines and anti-PD-1 or anti-CTLA-4 treatment had no remarkable effect on the viability of tumor cells. Using CCK-8, Precision Count Beads™ and Cell Trace™ violet proliferation assays, we proved significant increased proliferation of CIK cells in the presence of a combination of anti-PD-1 and anti-CTLA-4 antibodies compared to untreated CIK cells. The IFN-γ secretion increased significantly in the presence of A-498 and combinatorial blockade of PD-1 and CTLA-4 compared to nivolumab or ipilimumab monotreatment (p < 0.001). In conclusion, a combination of immune checkpoint inhibition with CIK cells augments cytotoxicity of CIK cells against renal cancer cells.


Monoballism associated with newly onset ketotic hyperglycemia.
Movement disorders as the initial symptoms of diabetes mellitus are rare. Here, we describe one of these rare manifestations of primary diabetes: a case of newly diagnosed diabetes mellitus in an old-age female patient with transient monoballismus during an episode of ketotic hyperglycemia.


Presence of additional Plasmodium vivax malaria in Duffy negative individuals from Southwestern Nigeria.
Malaria in sub-Saharan Africa (sSA) is thought to be mostly caused by Plasmodium falciparum. Recently, growing reports of cases due to Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax have been increasingly observed to play a role in malaria epidemiology in sSA. This in fact is due to the usage of very sensitive diagnostic tools (e.g. PCR), which have highlighted the underestimation of non-falciparum malaria in this sub-region. Plasmodium vivax was historically thought to be absent in sSA due to the high prevalence of the Duffy negativity in individuals residing in this sub-continent. Recent studies reporting detection of vivax malaria in Duffy-negative individuals from Mali, Mauritania, Cameroon challenge this notion. Following previous report of P. vivax in Duffy-negative individuals in Nigeria, samples were further collected and assessed RDT and/or microscopy. Thereafter, malaria positive samples were subjected to conventional PCR method and DNA sequencing to confirm both single/mixed infections as well as the Duffy status of the individuals. Amplification of Plasmodium gDNA was successful in 59.9% (145/242) of the evaluated isolates and as expected P. falciparum was the most predominant (91.7%) species identified. Interestingly, four P. vivax isolates were identified either as single (3) or mixed (one P. falciparum/P. vivax) infection. Sequencing results confirmed all vivax isolates as truly vivax malaria and the patient were of Duffy-negative genotype. Identification of additional vivax isolates among Duffy-negative individuals from Nigeria, substantiate the expanding body of evidence on the ability of P. vivax to infect RBCs that do not express the DARC gene. Hence, such genetic-epidemiological study should be conducted at the country level in order to evaluate the true burden of P. vivax in Nigeria.


Russian guidelines for the management of COPD: algorithm of pharmacologic treatment.
The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease. High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region. A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD. The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design. This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A-D for simplicity and clarity. At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed. Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues. Bronchodilators should not be discontinued except in the case of significant side effects. At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation. Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation.


[Ischemic retraction of the intrinsic muscles of the hand in leprosy (a trial of physiopathologic and therapeutic re-evaluation)].
An attempt of reevaluation of the ischemic contracture of intrinsic muscles is presented, study of a mechanism identical to the Volkman Syndrome (forearm muscles), etiopathogenic treatment (excision of infarcts) in the first stage and efficient palliative methods for the Swan neck fingers and deformity of the thumb.


[Bone levels of dibekacin].
Levels of an aminoglycoside, dibekacin, are studied in bone. Fifteen specimens were obtained by Tanzer trocar biopsy three hours after the ninth injection of dibekacin (1 mg/kg). Separation of cortical and spongy bone was not feasible owing to the small weight of specimens. Dibekacin concentrations were determined by microbiological assay. These concentrations were evaluated using a reference range in bone tissue determined with the same method and must be corrected according to blood levels. Dibekacin levels were 0.22 +/- 0.10 mg/l in healthy, non- contaminated specimens, and 1.70 and 1.80 mg/l in infected bone tissue.


Integrating knowledge, skills, and attitudes: professional training required for virtual reality therapists in palliative care.
Fully immersive virtual reality (VR) is an advanced technology increasingly studied and used in palliative care for symptom management. While the findings shed a positive light on its therapeutic potential, VR carries adverse effects, leading to ethical concerns. Based on the clinical experiences of a registered clinical psychologist who is also a certified thanatologist, we put forward a perspective on the importance of professional training for VR therapists in view of the possible risks posed by VR in palliative care. We propose professional trainings on knowledge, skills, and attitudes to ensure patients' safety while maximizing the therapeutic benefits of VR. Given the scarcity of reports on such an area, we hope this perspective article opens up discussions and contributes to current understanding and emerging future directions to ensure quality and ethical delivery of VR in palliative care.


[Design and application of a split first aid suit for heat stroke].
In the trend of global warming and the increasing number of participating in high-intensity sports, the incidence of heat stroke is increasing year by year. Heat stroke is categorized to the class of heat emergent diseases. If there is no quick and effective treatment, the mortality rate is as high as 50%. Early, rapid, and effective cooling is the key point in the treatment of heat stroke. The early recognition and rapid lowering the core body temperature to 38.9 centigrade within 30 minutes of exertional heat stroke results in better clinical outcome with the fewest complications, however, the "golden 30 minutes" is far from enough to complete emergency transport and evaluation. Therefore, it is urgent to develop a first aid suit for heat stroke suitable for field treatment and transportation, so as to achieve the treatment goal of early rapid and effective cooling in field environment. For this purpose, the medical staff of the department of critical care medicine of the Eighth Medical Center of the Chinese People's Liberation Army General Hospital designed and developed the split first aid suit, which is suitable for heat stroke patient in the harsh environment lacking medical supplies and water during transportation. The medical staff who designed the first aid suit obtained a National Utility Model Patent of China (ZL 2020 2 1627326.4). The split heat stroke first aid suit is composed of four main parts: a sleeveless coat, a hat, sleeves and wrapped pants. All of them are made by temperature changeable fabric which is a composite material made by fine porous silica gel particles and potassium nitrate. The cuffs of the sleeveless top of the clothes part and the sleeves are connected as a whole by the connecting pieces; and the front end of the hem of the clothes part and the wrapped trousers are also connected as a whole by the connecting pieces, which is convenient for fixing and transportation. In order to control the water injection quantity, the water injection bag and the corresponding components are designed to ensure the same amount of water can be injected to the heat stroke first aid suit at each time, so the same frigorific effect can be attainable. The service temperature is 14-18 centigrade, so it will not cause local frostbite to patients when used for a long time. This split-type first aid suit can be used in the movement, rescue and transportation of heat stroke patients. It is easy to carry and use with accurate cooling effect with low cost, moreover, it is reusable and can be widely used for on-site emergency and transportation of heat stroke patients.


Rituxan immunotherapy and zevalin radioimmunotherapy in the treatment of non-Hodgkin's lymphoma.
Immunotherapy with the anti-CD20 monoclonal antibody rituximab has been shown in clinical trials to be effective in the treatment of both indolent and aggressive non-Hodgkin's lymphomas (NHL). Recent studies have demonstrated improved clinical benefit with extended dose and maintenance therapies in patients with indolent lymphomas and chronic lymphocytic leukemia. Rituximab's label was recently expanded to include treatment of bulky disease, retreatment of patients previously treated with rituximab, and an eight-week extended treatment schedule. Rituximab has also been effectively combined with chemotherapy, resulting in higher response rates and longer response durations in randomized trials in patients with aggressive lymphoma. Studies continue to evaluate and expand the role of rituximab in the treatment of NHL, including its use in combined immunotherapy approaches and autologous stem cell transplant as well as in the treatment of autoimmune disorders. Radioimmunotherapy with the rituximab and ibritumomab tiuxetan (Zevalin) regimen was recently approved for the treatment of relapsed or refractory low-grade, follicular or CD20+ transformed NHL, including rituximab refractory follicular NHL. The regimen is delivered on an outpatient basis over the course of a week. Studies are currently exploring sequential dose therapy, radioimmunotherapy with rituximab maintenance, and ibritumomab tiuxetan radioimmunotherapy as part of autologous stem cell transplant. Current understanding of the mechanisms of action of rituximab and the use of rituximab and ibritumomab tiuxetan in patients with indolent and aggressive NHL will be discussed.


Infant doses from the transfer of radionuclides in mothers' milk.
Assessments of potential internal exposures of the child following radionuclide intakes by the mother require consideration of transfers during lactation as well as during pregnancy. Current ICRP work on internal dosimetry includes the estimation of radiation doses to newborn infants from radionuclides ingested in mothers' milk. Infant doses will be calculated for maternal intakes by ingestion or inhalation of the radionuclides, radioisotopes of 31 elements, for which fetal dose coefficients have been published. In this paper, modelling approaches are examined, concentrating on models developed for iodine, caesium, polonium, alkaline earth elements and the actinides. Comparisons of model predictions show maximum overall transfer to milk following maternal ingestion during lactation of about 30% of ingested activity for 131I, 20% for 45Ca and 137Cs, 10% for 90Sr, 1% for 210Po and low values of less than 0.01% for 239Pu and 241Am. The corresponding infant doses from milk consumption are estimated in preliminary calculations to be about two to three times the adult dose for 45Ca and 131I, 70-80% of the adult dose for 90Sr, about 40% for 137Cs, 20% for 210Po, and <0.1% for 239Pu and 241Am. Infant doses from radionuclides in breast milk are compared with doses to the offspring resulting from in utero exposures during pregnancy.


Prognostic relevance of number and ratio of metastatic lymph nodes in resected carcinoma of the ampulla of Vater.
To explore the prognostic relevance of the number and ratio of metastatic lymph nodes in resected Carcinoma of the ampulla of Vater (CAV). The clinical data of 155 patients who underwent pancreaticoduodenectomy (PD) for cancer of the ampulla of Vater between January 1990 and December 2010 were retrospectively analyzed. Kaplan-Meier method was used in survival analysis and Log rank method in comparison. Multivariate analysis was performed using Cox proportional hazards model. Among these 155 patients, the in-hospital mortality rate was 4.5%, lymph node positive disease was 21.3%, and the 5-year survival rate was 51.6%. Patients with a lymph node ratio (LNR) >20% were more likely to have tumor differentiation, depth of duodenal involvement, depth of pancreatic invasion, T-stage and TNM-Stage. The number of the metastatic lymph nodes is important prognostic factors of the CAV. Univariate analysis showed that the factors associated with the prognosis included tumor size (P=0.036), tumor differentiation (P=0.019), LNR (P=0.032), number of metastatic lymph nodes (P=0.024), lymph node metastasis (P=0.03), depth of pancreatic invasion (P=0.001), T-stage (P=0.002), TNM stage (P=0.001), elevated CA 19-9 (P=0.000), and jaundice (P=0.021). Multivariate analysis showed that the factors associated with the prognosis were the number of metastatic lymph nodes (P=0.032; RR: 1.283; 95% CI: 1.022-1.611), tumor size (P=0.043; RR: 1.736; 95% CI: 1.017-2.963), and elevated CA 19-9 (P=0.003; RR: 3.247; 95% CI: 1.504-7.010). LNR is a useful factor for predicting the prognosis of the radical treatment for CAV, whereas the number of metastatic lymph nodes is the most important factor. Further research on the locations, number, and LNR will be clinically meaningful to improve survival in patients with CAV.


Theoretical study of the reactivity of cesium with benzene and graphitic C(x)H(y) clusters.
The adsorption of a Cs atom on planar (C6H6 and C24H12) and nonplanar (C20H10 and C21H9) carbon clusters has been studied using the density-functional theory, with the local-density approximation and atomic pseudopotentials. Binding energies as a function of separation have been calculated for several configurations of the Cs atom on the different substrates. The adsorption on sites above the center of carbon rings is more stable than adsorption on top of carbon atoms and C-C bonds. In the case of the curved clusters, adsorption on the concave side is preferred compared to the convex side. The Cs bonding is stronger on the nonplanar clusters. The strength of the binding energy depends on two effects: the magnitude of the highest occupied molecular orbital-lowest unoccupied molecular orbital (LUMO) energy gap of the substrate, and the energy of the valence state of Cs relative to the LUMO of the substrate. Due to a favorable relative position of those two energy levels, charge transfer occurs from Cs to the two nonplanar clusters, and this provides an ionic contribution to the bonding. The analysis of the electronic density redistribution and of the local Fukui functions helps in the interpretation of the charge transfer and the reactivity.