beta-Thymosins are not simple actin monomer buffering proteins. Insights from overexpression studies.
beta-Thymosins are the currently favored candidates for maintaining the large actin monomer (G-actin) pool in living cells. To determine if beta-thymosin behaves like a simple G-actin buffering agent in the complex environment of a cell, we overexpressed thymosin beta10 (Tbeta 10) in NIH3T3 cells and determined the effect on the monomer/polymer equilibrium. Tbeta 10 is the predominant beta-thymosin isoform in the NIH3T3 cell line, and it is present in approximately equal molar ratio to profilin and cofilin/actin depolymerizing factor, two other well characterized actin monomer binding proteins. Clonal cell lines that overexpressed three times more Tbeta 10 had 23-33% more polymerized actin than control cells, and the filaments appeared thicker after staining with fluorescent phalloidin. There was no change in total actin, profilin, and cofilin/actin depolymerizing factor content. The overexpressing cells were more motile; they spread faster and had higher chemotactic and wound healing activity. Assuming that there is no compensatory inactivation of the other classes of monomer binding proteins, our paradoxical observation can be accounted for quantitatively by a parallel in vitro study (Carlier, M.-F., Didry, D., Erk, I., Lepault, J., Van Troys, L., Vanderkekove, J., Perelroizen, I., Yin, H. L., Doi, Y., and Pantaloni, D., (1996) J. Biol. Chem. 271, 9231-9239). beta-Thymosin at levels comparable with that found in the overexpressing cells binds actin filaments and decreases the critical concentration (C(c)) for actin polymerization. This reduces the monomer buffering ability of beta-thymosin, so that above a certain threshold an incremental increase in thymosin does not lead to a corresponding increase in G-actin. Furthermore, the decrease in C(c) reduces the buffering capacity of the other actin monomer binding proteins. As a consequence, an increase in beta-thymosin does not necessarily result in a proportionate increase in actin monomer content in a complex environment containing other actin monomer binding proteins. The outcome depends on the level of beta-thymosin expression relative to the composition of the other actin monomer binding protein. Our results suggest that beta-thymosins are not simple actin buffering proteins and that their biphasic action may have physiological significance.


A rapid malaria appraisal in the Venezuelan Amazon.
While the federal state of Amazonas bears the highest risk for malaria in Venezuela (2007: 68.4 cases/1000 inhabitants), little comprehensive information about the malaria situation is available from this area. The purpose of this rapid malaria appraisal (RMA) was to provide baseline data about malaria and malaria control in Amazonas. The RMA methodology corresponds to a rapid health impact assessment (HIA) as described in the 1999 Gothenburg consensus. In conjunction with the actors of the malaria surveillance system, all useful data and information, which were accessible within a limited time-frame of five visits to Amazonas, were collected, analysed and interpreted. Mortality from malaria is low (< 1 in 105) and slide positivity rates have stayed at the same level for the last two decades (15% +/- 6% (SD)). Active case detection accounts for ca. 40% of slides taken. The coverage of the censured population with malaria notification points (NPs) has been achieved in recent years. The main parasite is Plasmodium vivax (84% of cases). The proportion of Plasmodium falciparum is on the decline, possibly driven by the introduction of cost-free artemisinin-based combination therapy (ACT) (1988: 33.4%; 2007: 15.4%). Monitoring and documentation is complete, systematic and consistent, but poorly digitalized. Malaria transmission displayed a visible lag behind rainfall in the capital municipality of Atures, but not in the other municipalities. In comparison to reference microscopy, quality of field microscopy and rapid diagnostic tests (RDTs) is suboptimal (kappa < 0.75). Hot spots of malaria risk were seen in some indigenous ethnic groups. Conflicting strategies in respect of training of community health workers (CHW) and the introduction of new diagnostic tools (RDTs) were observed. Malaria control is possible, even in tropical rain forest areas, if the health system is working adequately. Interventions have to be carefully designed and the features of the particular local Latin American context considered.


Thermal regulation of phosphoenolpyruvate carboxylase and ribulose-1,5-bisphosphate carboxylase in c(3) and c(4) plants native to hot and temperate climates.
Exposure of leaf sections from 2-week-old seedlings of sorghum (Sorghum bicolor L.) (C(4) plant), corn (Zea mays L.) (C(4)), peanut (Arachis hypogaea L.) (C(3) plant), and soybean (Glycine max L.) (C(3)) to 40 or 45 degrees C for up to 4 hours resulted in significant increases in the levels of 102 kilodalton (C(4)), 52 kilodalton (C(3) and C(4)), and 15 kilodalton (C(3) and C(4)) polypeptides. These proteins comigrated, respectively, with authentic phosphoenolpyruvate carboxylase (PEPC) and the large (RLSU) and small (RSSU) subunits of ribulose-1,5-bisphosphate carboxylase (Rubisco) during both one- and two-dimensional SDS-PAGE and reacted with antisera raised against these enzymes. After 4 hours at 50 degrees C, levels of the polypeptides either remained relatively stable (PEPC, RLSU) or increased (RSSU) in sorghum and peanut (plants native to hot climates). In corn and soybean (plants native to temperate climates), levels of the proteins either fell sharply (corn) or showed strong evidence of incomplete processing and/or aggregation (soybean). In addition to changes in levels of the proteins, the activities of PEPC and Rubisco in extracts of leaves exposed to 50 degrees C fell by 84% and 11% of their respective control values in sorghum and by 54% each in peanut. In corn and soybean, the activities of both enzymes were depressed at 40 degrees C, with measured values at 50 degrees C not exceeding 5% of those from the nonstressed controls.


Isolated trochlear nerve palsy with midbrain hemorrhage.
Midbrain hemorrhage causing isolated fourth nerve palsy is extremely rare. Idiopathic, traumatic and congenital abnormalities are the most common causes of fourth nerve palsy. We report acute isolated fourth nerve palsy in an 18-year-old lady due to a midbrain hemorrhage probably due to a midbrain cavernoma. The case highlights the need for neuroimaging in selected cases of isolated trochlear nerve palsy.


Shortest paths on systems with power-law distributed long-range connections.
We discuss shortest-path lengths l(r) on periodic rings of size L supplemented with an average of pL randomly located long-range links whose lengths are distributed according to P(l) approximately l(-mu). Using rescaling arguments and numerical simulation on systems of up to 10(7) sites, we show that a characteristic length xi exists such that l(r) approximately r for r<xi but l(r) approximately r(theta(s)(mu)) for r>>xi. For small p we find that the shortest-path length satisfies the scaling relation l(r,mu,p)/xi=f(mu,r/xi). Three regions with different asymptotic behaviors are found, respectively: (a) mu>2 where theta(s)=1, (b) 1<mu<2 where 0<theta(s)(mu)<1/2, and (c) mu<1 where l(r) behaves logarithmically, i.e., theta(s)=0. The characteristic length xi is of the form xi approximately p(-nu) with nu=1/(2-mu) in region (b), but depends on L as well in region (c). A directed model of shortest paths is solved and compared with numerical results.


[Effects of electrical stimulation of SII and electroacupuncture on beta-endorphin contents in the perfusate from the nucleus centrum medianum of the thalamus in cats].
In order to probe into whether beta-endorphin is involved in descending modulation of the somatosensory area (SII) of the cerebral cortex on the nucleus centrum medianum (CM) of the thalamus and this mechanism of acupuncture analgesia, it was investigated that effects of electrical stimulation of SII and electroacupuncture on beta-endorphin content in the perfusate from the nucleus CM. Adult cats were randomly divided into three groups: control, electroacupuncture and electrical stimulation of SII. Push-pull perfusion technique was used to collect the perfusate from the nucleus CM beta-endorphin contents in the perfusate were determined with radioimmunoassay. The results indicated that beta-endorphin content in the perfusate was increased significantly by electrical stimulation of SII and not by electroacupuncture, suggesting that the beta-endorphin release from the nucleus CM was elevated by the stimulation of SII and was not influenced by electroacupuncture. It is indicated that beta-endorphin is possibly involved in the descending regulatory effect of electrical stimulation of SII on the nucleus CM, but is not involved in the regulatory effect of electroacupuncture on the nucleus CM.


Interaction of 5-lipoxygenase with cellular proteins.
5-Lipoxygenase (5LO) plays a pivotal role in cellular leukotriene synthesis. To identify proteins interacting with human 5LO, we used a two-hybrid approach to screen a human lung cDNA library. From a total of 1.5 x 10(7) yeast transformants, nine independent clones representing three different proteins were isolated and found to specifically interact with 5LO. Four 1.7- to 1.8-kb clones represented a 16-kDa protein named coactosin-like protein for its significant homology with coactosin, a protein found to be associated with actin in Dictyostelium discoideum. Coactosin-like protein thus may provide a link between 5LO and the cytoskeleton. Two other yeast clones of 1.5 kb encoded transforming growth factor (TGF) type beta receptor-I-associated protein 1 partial cDNA. TGF type beta receptor-I-associated protein 1 recently has been reported to associate with the activated form of the TGF beta receptor I and may be involved in the TGF beta-induced up-regulation of 5LO expression and activity observed in HL-60 and Mono Mac 6 cells. Finally, three identical 2.1-kb clones contained the partial cDNA of a human protein with high homology to a hypothetical helicase K12H4. 8 from Caenorhabditis elegans and consequently was named DeltaK12H4. 8 homologue. Analysis of the predicted amino acid sequence revealed the presence of a RNase III motif and a double-stranded RNA binding domain, indicative of a protein of nuclear origin. The identification of these 5LO-interacting proteins provides additional approaches to studies of the cellular functions of 5LO.


The Danish Bladder Cancer Database.
The aim of the Danish Bladder Cancer Database (DaBlaCa-data) is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC) in Denmark. All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results presented in this paper are predominantly from the 2013 population. In 2013, 970 patients were diagnosed with BC in Denmark and were included in a preliminary report from the database. A total of 458 (47%) patients were diagnosed with non-muscle-invasive BC (non-MIBC) and 512 (53%) were diagnosed with muscle-invasive BC (MIBC). A total of 300 (31%) patients underwent cystectomy. Among the 135 patients diagnosed with MIBC, who were 75 years of age or younger, 67 (50%) received neoadjuvent chemotherapy prior to cystectomy. In 2013, a total of 147 patients were treated with curative-intended radiation therapy. One-year mortality was 28% (95% confidence interval [CI]: 15-21). One-year cancer-specific mortality was 25% (95% CI: 22-27%). One-year mortality after cystectomy was 14% (95% CI: 10-18). Ninety-day mortality after cystectomy was 3% (95% CI: 1-5) in 2013. One-year mortality following curative-intended radiation therapy was 32% (95% CI: 24-39) and 1-year cancer-specific mortality was 23% (95% CI: 16-31) in 2013. This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database is able to identify Danish BC patients and monitor treatment and mortality. In the future, DaBlaCa-data will be a valuable data source and expansive observational studies on BC will be available.


Pitfalls and outcomes from accelerated wear testing of mechanical heart valves.
In 1990 Sorin Biomedica introduced a new bileaflet heart valve called the Bicarbon valve. This design was reported to eliminate wear in the hinge mechanism. Clinical quality Sorin Bicarbon, CarboMedics, St. Jude Medical, Duromedics and Jyros valves were obtained to test this claim and to compare the wear in the pivot of this new valve to other available heart valves. The valves were visually inspected then subjected to 4,000 cycles at a physiological beat rate in vitro. The valves were re-inspected then subjected to 400 million cycles in a Reul type accelerated wear tester. Scanning electron microscope photographs were taken of all contact areas at 40, 80, 120, 160, 200, 240, 280 and 400 million cycles. Wear marks on the inflow side of the Sorin, CarboMedics and St. Jude leaflets were measured and compared. Orifice wear was not quantified because of difficulty with measuring inside complex depressions. After 4,000 cycles of testing at a physiological beat rate the CarboFilmTM coating on the Sorin orifice showed signs of erosion. The other valve components only exhibited minor burnishing after 4,000 cycles. Following completion of 400 million cycles in an accelerated wear tester, approximately ten years in vivo, all valves showed significant wear. The inflow face of the pivot on the Sorin Bicarbon leaflets exhibited the deepest wear marks. The CarboFilm coating on the Sorin Bicarbon orifices was removed from most areas of leaflet contact. The transition between the remaining coating and the eroded areas created a rough edge. The tips of the Sorin leaflets contacted the bottom of the orifice pivot, in contrast to the St. Jude Medical and CarboMedics designs, which had minimal contact between the leaflet and the orifice.


Genetics and evidence for an esterase-associated mechanism of resistance to indoxacarb in a field population of diamondback moth (Lepidoptera: Plutellidae).
Bioassays (at generation G2) with a newly collected field population (designated CH3) of Plutella xylostella L. from farmers' fields in the Cameron Highlands, Malaysia, indicated resistance ratios of 813-, 79-, 171-, 498- and 1285-fold for indoxacarb, fipronil, spinosad, deltamethrin and Bacillus thuringiensis toxin Cry1Ac respectively compared with a laboratory susceptible population (Lab-UK). At G2 the field-derived population was divided into two subpopulations: one was selected (G2 to G7) with indoxacarb (indoxa-SEL), while the second was left unselected (UNSEL). A significant reduction in the resistance ratio for each compound was observed in UNSEL at G8. For indoxa-SEL, bioassays at G8 found that selection with indoxacarb gave a resistance ratio of 2594 compared with Lab-UK and of 90 compared with UNSEL. The toxicity of fipronil, spinosad and deltamethrin was not significantly different in indoxa-SEL at G8 compared with G2 but was significantly greater than UNSEL at G8. The toxicity of Cry1Ac was significantly reduced in indoxa-SEL at G8 compared with G2 but was also significantly greater than UNSEL at G8. This suggests that indoxacarb selection maintained resistance to these compounds in the indoxa-SEL population. Synergist studies indicated that resistance to indoxacarb in indoxa-SEL was esterase associated. Logit regression analysis of F1 reciprocal crosses between indoxa-SEL and Lab-UK indicated that resistance to indoxacarb was inherited as an autosomal, incompletely recessive (D(LC) = 0.35) trait. Tests of monogenic inheritance suggested that resistance to indoxacarb was controlled by a single locus.


Artistic productivity and creative thinking in Parkinson's disease.
Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic-like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. Mean TTCT score of PD-c was found to be similar to HC (169.4±51.6 vs. 170.2±69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4±46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy.


Trends in three-year survival following acute myocardial infarction, 1983-1992.
As part of an investigation into the decline in coronary heart disease mortality rates in New Zealand, we examined long-term survival trends following acute myocardial infarction. A 3-year follow-up of patients on a community-based register of coronary heart disease for the period 1983-1992 in Auckland, New Zealand, part of the World Health Organization's MONICA (multinational Monitoring of Trends and Determinants in Cardiovascular Disease) Project, has been completed. The 3-year survival status of acute myocardial infarction patients aged 25-64 years who were alive 28 days after their first event has been obtained. The 2940 men and women followed for 3 years after an acute myocardial infarction showed significant steady improvement over the 10-year study period (P=0.004). The 3-year survival of patients registered in 1983-1984 was 86% and by 1991-1992 it was 92%. The gains in long-term survival following acute myocardial infarction are statistically significant but contribute only marginally to the decline in coronary heart disease death rates in Auckland since most deaths occur in the first 28 days after the event.


Immunopharmacological studies on Picrorhiza kurroa Royle-ex-Benth. Part III: Adrenergic mechanisms of anti-inflammatory action.
Nature of adrenergic mechanisms contributing to anti-inflammatory effect of Picrorhiza kurroa suggested from earlier studies was explored in Wistar albino rats. Water soluble fraction of alcoholic extract of rhizomes (PK) potentiated castor oil-catharsis on oral administration but direct subplanter PK-injections failed to exhibit any local irritancy and oedema. Propranolol pretreatment counteracted while phentolamine enhanced anti-inflammatory effect of PK in carrageenin-induced inflammation. 6-hydroxy-dopamine pretreatment antagonised the said PK-effect and in such animals both ephedrine and isoprenaline augmented anti-inflammatory effect of PK, the former interaction being more conspicuous. PK-treatment of rats did not influence adrenaline uptake by lung slices in vitro. The results suggest that a non-neural augmentation of beta-adrenoceptor function or consequent cellular events mediates the anti-inflammatory effect of PK.


[General process of aging].
Genetic instability is considered to be a fundamental factor in the ageing process. This instability results from the accumulation of damage caused to DNA, and this is demonstrated by the relationship between longevity and DNA repair. However, the accumulation of simple somatic mutations does not explain all the experimental findings. We are forced to take into account, not only the instability of the genes, but also the instability of the expression of the genes. Knowing that the expression of genes depends on interactions between DNA and proteins, we can see that genetic instability is based, at least in part, on protein synthesis. Attention has recently been drawn to the mechanism of transcription and notably of messenger DNA division. At the level of translation, the rate at which messenger DNA is degraded and various elongation factors necessary for ribosome activity have also been implicated. Post-translational changes of proteins by glycosylation or oxidation may be involved in the progressive accumulation of errors, which finally leads to cell death.


Syndrome-causing mutations in Werner syndrome.
Complete loss of function in the WRN: RecQ3 DNA/RNA helicase gene causes Werner Syndrome (WS). WS patients with genetic instability manifest an early onset of age-related diseases including diabetes mellitus (DM), osteoporosis, atherosclerosis, and malignancy as well as early death. In 1,420 patients, WS was reported to be associated with chromosomal abnormality syndrome and other genetic diseases including Klinefelter syndrome in 2 patients, retinitis pigmentosa in 3, Wilson's disease in 1, xeroderma pigmentosum in 3, and porokeratosis Mibelli in 1. These clinical findings may support the concept of genetic instability in WS.


Serum Metabolomic Profiling Reveals Biomarkers for Early Detection and Prognosis of Esophageal Squamous Cell Carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the most common aggressive malignancies worldwide, particularly in northern China. The absence of specific early symptoms and biomarkers leads to late-stage diagnosis, while early diagnosis and risk stratification are crucial for improving overall prognosis. We performed UPLC-MS/MS on 450 ESCC patients and 588 controls consisting of a discovery group and two validation groups to identify biomarkers for early detection and prognosis. Bioinformatics and clinical statistical methods were used for profiling metabolites and evaluating potential biomarkers. A total of 105 differential metabolites were identified as reliable biomarker candidates for ESCC with the same tendency in three cohorts, mainly including amino acids and fatty acyls. A predictive model of 15 metabolites [all-trans-13,14-dihydroretinol, (±)-myristylcarnitine, (2S,3S)-3-methylphenylalanine, 3-(pyrazol-1-yl)-L-alanine, carnitine C10:1, carnitine C10:1 isomer1, carnitine C14-OH, carnitine C16:2-OH, carnitine C9:1, formononetin, hyodeoxycholic acid, indole-3-carboxylic acid, PysoPE 20:3, PysoPE 20:3(2n isomer1), and resolvin E1] was developed by logistic regression after LASSO and random forest analysis. This model held high predictive accuracies on distinguishing ESCC from controls in the discovery and validation groups (accuracies > 89%). In addition, the levels of four downregulated metabolites [hyodeoxycholic acid, (2S,3S)-3-methylphenylalanine, carnitine C9:1, and indole-3-carboxylic acid] were significantly higher in early cancer than advanced cancer. Furthermore, three independent prognostic markers were identified by multivariate Cox regression analyses with and without clinical indicators: a high level of MG(20:4)isomer and low levels of 9,12-octadecadienoic acid and L-isoleucine correlated with an unfavorable prognosis; the risk score based on these three metabolites was able to stratify patients into low or high risk. Moreover, pathway analysis indicated that retinol metabolism and linoleic acid metabolism were prominent perturbed pathways in ESCC. In conclusion, metabolic profiling revealed that perturbed amino acids and lipid metabolism were crucial metabolic signatures of ESCC. Both panels of diagnostic and prognostic markers showed excellent predictive performances. Targeting retinol and linoleic acid metabolism pathways may be new promising mechanism-based therapeutic approaches. Thus, this study would provide novel insights for the early detection and risk stratification for the clinical management of ESCC and potentially improve the outcomes of ESCC.


Artepillin C Reduces Allergic Airway Inflammation by Induction of Monocytic Myeloid-Derived Suppressor Cells.
Propolis is a natural product produced by bees that is primarily used in complementary and alternative medicine and has anti-inflammatory, antibacterial, antiviral, and antitumoral biological properties. Some studies have reported the beneficial effects of propolis in models of allergic asthma. In a previous study, our group showed that green propolis treatment reduced airway inflammation and mucus secretion in an ovalbumin (OVA)-induced asthma model and resulted in increased regulatory T cells (Treg) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) frequencies in the lungs, two leukocyte populations that have immunosuppressive functions. In this study, we evaluated the anti-inflammatory effects of artepillin C (ArtC), the major compound of green propolis, in the context of allergic airway inflammation. Our results show that ArtC induces in vitro differentiation of Treg cells and monocytic MDSC (M-MDSC). Furthermore, in an OVA-induced asthma model, ArtC treatment reduced pulmonary inflammation, eosinophil influx to the airways, mucus and IL-5 secretion along with increased frequency of M-MDSC, but not Treg cells, in the lungs. Using an adoptive transfer model, we confirmed that the effect of ArtC in the reduction in airway inflammation was dependent on M-MDSC. Altogether, our data show that ArtC exhibits an anti-inflammatory effect and might be an adjuvant therapy for allergic asthma.


Functional correlates of fiber architecture of the lateral caudal musculature in prehensile and nonprehensile tails of the platyrrhini (primates) and procyonidae (carnivora).
Prehensile-tailed platyrrhines (atelines and Cebus) and procyonids (Potos) display bony tail features that have been functionally and adaptively linked to their prehensile behaviors, particularly the need to resist relatively greater bending and torsional stresses associated with supporting their body weight during suspensory postures. We compared fiber architecture of the mm. intertransversarii caudae (ITC), the prime tail lateral flexors/rotators, in 40 individuals distributed across 8 platyrrhine and 2 procyonid genera, divided into one of two groups: prehensile or nonprehensile. We tested the hypothesis that prehensile-tailed taxa exhibit relatively greater physiologic cross-sectional areas (PCSAs) to maintain tail suspensory postures for extended periods. As an architectural trade-off of maximizing force, we also predicted prehensile-tailed taxa would exhibit relatively shorter, more pinnate fibers, and a lower mass to tetanic tension ratio (Mass/P(O)). Prehensile-tailed taxa have relatively higher PCSAs in all tail regions, indicating their capacity to generate relatively greater maximum muscle forces compared to nonprehensile-tailed taxa. Contrary to our predictions, there are no group differences in pinnation angles, fiber lengths or M/P(O) ratios. Therefore, the relatively greater prehensile PCSAs are driven largely by relative increase in muscle mass. These findings suggest that relatively greater ITC PCSAs can be functionally linked to the need for prehensile-tailed taxa to suspend and support their body weight during arboreal behaviors. Moreover, maximizing ITC force production may not come at the expense of muscle excursion/contraction velocity. One advantage of this architectural configuration is it facilitates suspension of the body while simultaneously maximizing tail contact with the substrate.


Multiple apocrine hidrocystomas: treatment with carbon dioxide laser vaporization.
Apocrine hidrocystoma is a benign cystic tumour with apocrine differentiation. Although most cases are solitary tumours, multiple tumours may occur. Surgical removal is the usual treatment for apocrine hidrocystoma, but it may be troublesome and disfiguring in cases with multiple tumours. To determine the efficacy and cosmetic outcome of carbon dioxide laser vaporization in the treatment of multiple apocrine hidrocystomas. A total of 11 lesions in three adult patients were treated with carbon dioxide laser vaporization using a continuous and defocused mode, with a power density of 5 J/cm(2). The lesions were localized lateral to the outer canthus, on the free edge of the eyelids, and on the ear. Only a single session of treatment was performed for each lesion. Photographic controls were taken before and after treatment. The lesions cleared after laser treatment without residual changes, and a successful cosmetic result was obtained. Carbon dioxide laser is an efficient method of the treatment for multiple apocrine hidrocystomas.


Solid lipid nanoparticles containing 7-ethyl-10-hydroxycamptothecin (SN38): Preparation, characterization, in vitro, and in vivo evaluations.
7-Ethyl-10-hydroxycamptothecin (SN38) is a biologically active metabolite of irinotecan. Due to the variability of irinotecan metabolism rate to SN38, and poor solubility of this compound in pharmaceutically acceptable solvents, SN38 has not been successfully used in the clinic. In the present study, we prepared solid lipid nanoparticle (SLN) formulations containing SN38 and evaluated the in vitro and in vivo efficacy of these nanoparticles. SLNs and PEGylated SLNs containing SN38 (SLN-SN38 and PEG-SLN-SN38) were prepared using ultrasonication technique. Nanoparticles were characterized for size, zeta potential, and drug encapsulation efficiency. In vitro cytotoxicity of these compounds was evaluated in two colorectal carcinoma cell lines, namely C-26 and HT-116. In vivo antitumor efficacy of the formulations was evaluated in C-26 xenograft tumor mice models. Mice survival was also explored through 60days post IV injection. Mean size of SLN-SN38 and PEG-SLN-SN38 was around 103 and 131nm, respectively. Polydispersity index (PDI) for all the formulations was around 0.2 and zeta potential was negative (-5 to -15mV). Nearly 90% of the drug was encapsulated in SLNs. SLN-SN38 and PEG-SLN-SN38 compared to irinotecan were significantly more toxic to C-26 and HT-116 cell lines after 48h of exposure. Calculation of IC50 suggests higher sensitivity of HT-116 cells than C-26 cells to SLN-SN38 and PEG-SLN-SN38. Tumor inhibitory efficacy presented the highest efficacy in SLN-SN38. However, both SLN-SN38 and PEG-SLN-SN38 carriers showed higher efficiency to inhibit tumors compared to irinotecan (25mg/kg).


Respiratory care billing using a personal digital assistant.
In 2003 I reported how my respiratory care department at Tufts-New England Medical Center developed an inexpensive, in-house, computerized clinical-information-management system, in which the respiratory therapists carry handheld computers during their rounds, entering clinical information into the handhelds as they work and later downloading that information to a database in a desktop computer. Now we have added a billing module to our customized software. This article describes the design, use, and attributes of this billing system, including improved charge-capture, which increased department revenue substantially. Our system has several other important advantages over traditional billing systems.


Capacity and use of diagnostics and treatment for patients with severe acute respiratory infections in the pre-COVID-19 era in district and provincial hospitals in Viet Nam.
To describe the burden of severe acute respiratory infection (SARI) and the infrastructure and current practices of SARI management in hospitals in Viet Nam. We conducted a short observational study at critical care units (CCUs) in 32 district hospitals and 16 provincial hospitals in five provinces in Viet Nam from March to July 2019. We collected data on hospital equipment and medicines used in SARI management. At the patient level, data were collected for 14 consecutive days on all patients presenting to CCUs, including information on demographics, intervention and treatment within 24 hours of CCU admission and 7-day outcome. There were significant differences between district and provincial hospitals in the availability of microbial culture, rapid influenza diagnostic tests, inflammatory markers and mechanical ventilation. Among 1722 eligible patients admitted to CCUs, there were 395 (22.9%) patients with SARI. The median age of SARI patients was 74 (interquartile range: 58-84) years; 49.1% were male. Although systemic antibiotics were available in all hospitals and were empirically given to 93.4% of patients, oseltamivir was available in 25% of hospitals, and only 0.5% of patients received empiric oseltamivir within 24 hours of admission. The 7-day mortality was 6.6% (26/395). Independent factors associated with 7-day mortality were septic shock and requiring respiratory support within 24 hours of admission. SARI is a major burden on CCUs in Viet Nam. Barriers to delivering quality care include the limited availability of diagnostics and medication and non-protocolized management of SARI in CCUs.


The Venom of Philippine Tarantula (Theraphosidae) Contains Peptides with Pro-Oxidative and Nitrosative-Dependent Cytotoxic Activities against Breast Cancer Cells (MCF-7) In Vitro.
Breast cancer is a multifactorial disease that affects women worldwide. Its progression is likely to be executed by oxidative stress wherein elevated levels of reactive oxygen and nitrogen species drive several breast cancer pathologies. Spider venom contains various pharmacological peptides which exhibit selective activity to abnormal expression of ion channels on cancer cell surface which can confer potent anti-cancer activities against this disease. Venom was extracted from a Philippine tarantula by electrostimulation and fractionated by reverse phase-high performance liquid chromatography (RP-HPLC). Venom fractions were collected and used for in vitro analyses such as cellular toxicity, morphological assessment, and oxidative stress levels. The fractionation of crude spider venom generated several peaks which were predominantly detected spectrophotometrically and colorimetrically as peptides. Treatment of MCF-7 cell line of selected spider venom peptides induced production of several endogenous radicals such as hydroxyl radicals (•OH), nitric oxide radicals (•NO), superoxide anion radicals (•O2-) and lipid peroxides via malondialdehyde (MDA) reaction, which is comparable with the scavenging effects afforded by 400 µg/mL vitamin E and L-cysteine (p<0.05). Concomitantly, the free radicals produced decrease the mitochondrial membrane potential and metabolic activity as detected by rhodamine 123 and tetrazolium dye respectively (p>0.05). This is manifested by cytotoxicity in MCF-7 cells as seen by increase in membrane blebbing, cellular detachment, caspase activity and nuclear fragmentation. These data suggest that the Philippine tarantula venom contains peptide constituents exhibiting pro-oxidative and nitrosative-dependent cytotoxic activities against MCF-7 cells and can indicate mechanistic insights to further explore its potential application as prooxidants in cancer therapy.<br />.


Clinically silent electrocardiographic abnormalities and risk of primary cardiac arrest among hypertensive patients.
Whether continuous ECG indexes that reflect the severity of left ventricular hypertrophy (LVHI), myocardial injury (CIIS), and QT-interval prolongation (QTI) are associated with the risk of primary cardiac arrest among hypertensive patients, independent of conventional binary ECG criteria, remains unknown. We conducted a population-based case-control study among patients who were free of clinically recognized heart disease and who received care at a health maintenance organization. Cases (n = 131) were treated hypertensive patients who had had a primary cardiac arrest between 1977 and 1990. Controls (n = 562) were a stratified random sample of treated hypertensive patients. Resting ECGs were reviewed to estimate the severity of left ventricular hypertrophy, myocardial injury, and QT-interval prolongation on the basis of the algorithms of the Novacode ECG classification system. After adjustment for other risk factors and binary ECG criteria for the abnormalities, the LVHI, CIIS, and QTI scores were directly related to the risk of primary cardiac arrest. In a comparison of the 80th with the 20th percentile score for the LVHI, the risk was increased 40% (odds ratio, 1.4; 95% CI, 1.0 to 2.0); for the CIIS, the risk was increased 70% (odds ratio, 1.7; 95% CI, 1.2 to 2.5); and for the QTI, the risk was increased 80% (odds ratio, 1.8; 95% CI, 1.3 to 2.7). Our findings suggest that continuous ECG indexes that reflect left ventricular hypertrophy, myocardial injury, and QT-interval prolongation are directly related to the risk of primary cardiac arrest among hypertensive patients without clinically recognized heart disease. Binary ECG criteria may underestimate the prognostic importance of these pathophysiological abnormalities.


Evidence for a novel type 1 diabetes susceptibility locus on chromosome 8.
Type 1 diabetes results from a combination of genetic susceptibility and environmental exposures. Susceptibility loci other than HLA and the insulin gene remain to be identified to account for the degree of familial clustering observed in this disorder. Early genome-wide scans provided suggestive evidence of linkage on chromosome 8q, prompting detailed analysis of this region. A total of 20 microsatellite markers spanning an 88-cM region of 8q11-24 were genotyped in 24 type 1 diabetes pedigrees from Wisconsin that contained 39 affected sib-pairs. Multipoint linkage analyses provided close to suggestive evidence of linkage, with a multipoint logarithm of odds score (MLS) of 2.4 and Genehunter nonparametric logarithm of odds score (NPL) of 2.7 (P = 0.003). There is also evidence of linkage disequilibrium at peak marker D8S1823 for the 217bp allele (P = 0.037) using the pedigree disequilibrium test. Although our sample size was small, the multiple tests were consistent and our preliminary results suggested that 8q24 may harbor a novel population-specific type 1 diabetes susceptibility gene. Continued investigation of this region for a novel type 1 diabetes susceptibility gene appears justified.


Management of tattoos in the operative field.
Tattooing is increasingly common in Western society. The aim of the study was to create an overview of the surgical options when a tattoo is present in the operative site and to present an algorithm for the surgical plan.A literature-based study was conducted, using the Pubmed database. The following search terms have been used: "tattoo" in combination with "incision," "scar," and "surgery." Apart from the literature, we also used our own clinical experience with the tattoos.An overview is presented on the different options when a tattoo is at risk because of a surgical intervention. An algorithm is presented to help surgeons to choose the best option before the operation.By realizing that a tattoo can be of great value to a patient and by using surgical skills to preserve the tattoo as much as possible, it becomes possible to increase patient satisfaction in these difficult cases.


Women's perceived work environment after stress-related rehabilitation: experiences from the ReDO project.
The study aimed to investigate (a) if women's perceptions of their work environment changed during a 16-week rehabilitation period and at a 12-month follow-up; (b) whether such changes were related to outcomes in terms of return to work, well-being and valued occupations. Eighty-four gainfully employed women on sick-leave due to stress-related disorders responded to instruments assessing perceptions of the work environment, well-being (self-esteem, self-mastery, quality of life, perceived stress, self-rated health) and perceived occupational value. Data about return to work were collected from registers. Non-parametric statistics were used. The increase in the women's ratings of their work environment was non-significant between baseline and completed rehabilitation but was statistically significant between baseline and the 12-month follow-up. No relationships were found between changes in perceptions of the work environment and outcomes after the rehabilitation. At the follow-up, however, there were associations between perceived work environment changes in a positive direction and return to work; improved self-esteem, self-mastery, quality of life, perceived occupational value and self-rated health; and reduced stress. It seems important to consider the work environment in rehabilitation for stress-related problems, and a follow-up appears warranted to detect changes and associations not visible immediately after rehabilitation. Work environment Perceptions of the work environment seem important for return to work, although other factors are likely to contribute as well. Perceptions of the work environment are associated with several aspects of well-being. When developing rehabilitation interventions a focus on the clients' perceptions of their work environment seems vital.


Chronic pelvic pain and depression.
The psychological and clinical characteristics of 29 women who underwent laparoscopy for chronic pelvic pain (CPP) have been studied. Patients (n = 11) with CPP without obvious organic pathology showed a significantly higher mean score at the Zung Self-Rating Depression Scale and more somatic symptoms which usually accompany depression than patients (n = 18) with CPP in whom pathology was found; they also showed higher frequencies for depressive disorders in personal anamnesis and for 'depression spectrum disorders' in family history. No differences between the two groups emerged for anxiety, somatization and inadequacy as measured by the Kellner-Sheffield Symptom Rating Test. Through a comparison with a group of women affected with another type of idiopathic chronic pain, and on the basis of the above reported results, the authors suggest that CPP without obvious organic pathology might be an expression of a depressive disorder.


Transcriptional linkage of Haloferax volcanii proteasomal genes with non-proteasomal gene neighbours including RNase P, MOSC domain and SAM-methyltransferase homologues.
Comparative genomics reveals a common theme of 20S proteasome and proteasome-activating nucleotidase genes dispersed throughout archaeal genomes yet arranged in conserved linkages with gene homologues of translation and/or transcription machineries. To provide biological evidence for these linkages as well as insight into proteasome operon organization, transcripts of the five proteasomal genes of the halophilic archaeon Haloferax volcanii were analysed by Northern (RNA) blotting, RT-PCR and primer extension. These included psmA, psmB and psmC, encoding the 20S proteasomal subunits alpha1, beta and alpha2, as well as panA and panB, encoding the PanA and PanB proteasome-activating nucleotidase proteins, respectively. All five of these genes are dispersed throughout the H. volcanii genome. For each proteasomal gene, a distinct transcript was detected by Northern blotting that was similar in size to the respective coding region. For both psmA and psmC, an additional transcript was detected that was 1.34 and 0.85 kb greater, respectively, than the coding region. Further analysis by Northern blotting and RT-PCR revealed that psmA was co-transcribed with genes encoding a Pop5 homologue of the RNase P endoRNase as well as an S-adenosylmethionine (SAM)-dependent methyltransferase. Likewise, psmC was co-transcribed with a downstream gene encoding a molybdenum cofactor sulfurase C-terminal (MOSC) domain protein. Additional proteasomal and neighbouring gene-specific transcriptional linkages were detected by RT-PCR. These results provide the first evidence that proteasome and tRNA modification genes are co-transcribed, reveal that a number of additional enzymes including those predicted to facilitate metal-sulfur cluster assembly are co-regulated with proteasomes at the transcriptional level, and provide further insight into proteasome gene transcription in archaea.


Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy.
To clarify the role of choroidal vascular abnormalities in central serous chorioretinopathy (CSC) in active stage, remission, and recurrence. Indocyanine green angiography and fluorescein angiography were performed in 105 eyes (104 patients) with active CSC. Forty-six patients were followed up for 6 to 48 months (mean +/- standard deviation, 22.5 +/- 8.9 months) with repeated angiography (mean +/- standard deviation, 3.5 +/- 1.5 times). Indocyanine green angiography and fluorescein angiography also were performed during remission in all 46 eyes with CSC and during recurrent CSC in 6 eyes. Unaffected fellow eyes underwent angiographic examinations in all patients. In active CSC, indocyanine green angiography showed a choroidal filling delay (71%), venous dilation (61%), and focal choroidal hyperfluorescence (96%) surrounding leakage from the retinal pigment epithelium. Focal choroidal hyperfluorescence was present in unaffected areas of affected eyes (55%). The choroidal venous dilation (36%) and choroidal hyperfluorescence (62%) were noted even in unaffected fellow eyes. These choroidal abnormalities persisted during remission after leakage ceased throughout the follow-up period. In the six patients with recurrent CSC, new leakage developed in the areas of persistent choroidal hyperfluorescence. Central serous chorioretinopathy developed in the unaffected fellow eye in one of these six patients. Choroidal vascular abnormalities persist in both eyes even after leakage from the retinal pigment epithelium ceases. Central serous chorioretinopathy may recur in areas of choroidal vascular abnormalities.


Verbal and visual memory in patients with early Parkinson's disease: effect of levodopa.
The effect of initiation of levodopa therapy on the memory functions in patients with Parkinson's disease remains poorly understood. To evaluate the effect of initiation of levodopa therapy on memory, in patients with early Parkinson's disease. Prospective case control study. Seventeen patients with early Parkinson's disease were evaluated for verbal memory using Rey's auditory verbal learning test, and visual memory using the Benton's visual retention test and Form sequence learning test. UPDRS scores, Hoehn and Yahr's Staging and Schwab and England scores of Activities of daily living. Hamilton's depression rating scale and MMSE were also evaluated. Six controls were also evaluated according to similar study protocol. Levodopa was then prescribed to the cases. Same tests were repeated on all the subjects after 12 weeks. The mean age of the patients was 59.8 (+ 12.9 yrs); mean disease duration of 3.26 (+ 2.06 yrs). The mean UPDRS scores of patients were 36.52 (+ 15.84). Controls were of a similar age and sex distribution. A statistically significant improvement in the scores on the UPDRS, Hamilton's depression scale, Schwab and England scale, and a statistically significant deterioration in the scores of visual memory was observed in patients with PD after starting levodopa, as compared to their baseline scores. There was no correlation between degree of deterioration and the dose of levodopa. Initiation of levodopa therapy in patients with early and stable Parkinson's disease is associated with deterioration in visual memory functions, with relative preservation of the verbal memory.


Pathogen Survey of Pulp and Paper Mill Biosolids Compared with Soils, Composts, and Sewage Biosolids.
Regulatory policies to manage land application of organic materials are risk based, with focus on the quality of these residuals. The Ontario Ministry of the Environment and Climate Change (MOECC) determined that limited information was available on pulp and paper biosolids (PPB) with respect to human enteric pathogens. To address this data gap, MOECC conducted an extensive survey (2005-2006) across Ontario to characterize the microbiological quality of PPB. Quantitative testing was performed for fecal indicators (, enterococci, ) and enteric pathogens (, , , and ) using matrix-validated methods. Comparative benchmark materials (soils and soil amendments) were analyzed concurrently for risk comparison. Results showed that detection rates in PPB were low, 5 to 25% for pathogens and <55% for . , and were found at low frequency (6-8% of samples) and at low mean concentrations (2 most probable number g dry wt., 9 oocysts g dry wt., and 7 cells g dry wt., respectively). was more frequently observed (19% of samples), with a mean of 30 cysts g dry wt. Pathogen concentrations in PPB were generally equivalent to or higher than those in soils, composts, and pelletized sewage biosolids but significantly lower than in sewage biosolids. levels exceeded standards (1000 colony-forming units g dry wt.) in one-third of samples, most often in fresh PPB rather than stored and lagoon solids. Microbial quality of PPB across all surveyed mills tended to be variable and sector- and/or site-specific but in many cases would not consistently meet Canadian federal fertilizers standards. These findings were important to inform Ontario's nutrient management regulations, supporting classification of PPB as higher pathogen risk than compost and commercial fertilizers.


Structural and functional characterization of a monoclonal antibody blocking TIGIT.
TIGIT is an immune checkpoint receptor that is expressed on subsets of activated T cells and natural killer (NK) cells. Several ligands for TIGIT, including poliovirus receptor (PVR), are expressed on cancer cells and mediate inhibitory signaling to suppress antitumor activities of the immune cells. Many studies support that the TIGIT signaling is a potential target for cancer immunotherapy. We developed an IgG4-type monoclonal antibody against human TIGIT, designated as MG1131, using a phage display library of single-chain variable fragments (scFvs). MG1131 interacts with TIGIT much more tightly than PVR does. The crystal structure of a scFv version of MG1131 bound to TIGIT was determined, showing that MG1131 could block the PVR-TIGIT interaction and thus the immunosuppressive signaling of TIGIT. Consistently, MG1131 is bound to TIGIT-expressing cells and interferes with PVR binding to these cells. Moreover, MG1131 increased NK cell-mediated tumor killing activities, inhibited immunosuppressive activity of regulatory T (Treg) cells from healthy donors, and restored interferon-γ secretion from peripheral blood mononuclear cells derived from multiple myeloma patients. MG1131 also increased T cell infiltration to the tumor site and inhibited tumor growth in mice. Collectively, these data indicate that MG1131 modulates the effector functions of T cells and NK cells positively and Treg cells negatively.


Spatially resolved imaging of myocardial function with strain-encoded MR: comparison with delayed contrast-enhanced MR imaging after myocardial infarction.
Strain-encoded magnetic resonance (MR) imaging was prospectively evaluated for direct imaging of systolic myocardial strain and compared with cross-registered delayed contrast material-enhanced MR imaging in five healthy volunteers and nine patients with infarction. Local contractile performance was decreased in infarcted myocardium versus that in remote and adjacent myocardium (P < .01) and in adjacent versus remote myocardium (P < .05). The extent of dysfunctional myocardium, as assessed with strain-encoded MR imaging, was greater than that of hyperenhancement, as assessed with delayed contrast-enhanced MR imaging (P < .05). Strain values obtained with strain-encoded MR imaging were strongly correlated with those obtained with three-dimensional tagged MR imaging (r = 0.75, P < .001). Strain-encoded MR imaging provides spatially resolved (1.5 x 2.5-mm) imaging and measurement of myocardial strain in humans without the need for postprocessing, which may improve routine comprehensive evaluation of myocardial viability.


Influence of pre and postpartum alpha-tocopherol supplementation on milk yield, milk quality, and udder health of Jersey crossbred cows at tropical lower Gangetic region.
Alpha-tocopherol supplementation influences milk yield, milk quality, and udder health of dairy cows, which needs to be investigated for Jersey crossbred cows at hot-humid climate. Therefore, the present study was framed with an objective to study the effect of pre and postpartum Alpha-tocopherol supplementation on milk yield, milk quality, and udder health status of Jersey crossbred cows at tropical climate. For this study, 19 similar parity, body condition score, and production level dairy animals were separated randomly into three groups, namely, Control, T1 and T2. Control group (no supplementation) was compared with two treatment groups, namely, T1 and T2. Supplementation of Alpha-tocopherol was done in concentrate fed to the animals (at 1 g/cow/day) 30 days prepartum to 30 days postpartum in T1 and 30 days prepartum to 60 days postpartum in T2 groups. Observations were taken for different parameters up to 5 months of lactation. Statistically analyzed data revealed that overall significantly (p<0.01) more milk production was found in T2, followed by T1 than the control group. Overall significantly (p<0.01) lower somatic cell counts and modified California mastitis tests were recorded in T2, followed by T1 than the control group. Overall significantly (p<0.01), better milk quality in terms of methylene blue reduction test was found in T2, followed by T1 than control groups. Differences in the milk composition of all three groups were non-significant (p>0.05). Supplementation of Alpha-tocopherol during prepartum to initial lactation period may enhance milk yield, milk quality, and udder health status of Jersey crossbred cows at the tropical lower Gangetic region.


Nutritional problems and their non-pharmacological treatment in adults undergoing haematopoietic stem cell transplantation-A systematic review.
This systematic review aimed to identify the most relevant problems related to malnutrition in adult patients undergoing haematopoietic stem cell transplantation (HSCT) and to identify non-pharmacological interventions to treat these problems. A systematic search for each research question was performed in MEDLINE, CINAHL, Embase, the Cochrane Library, Google Scholar and reference lists in the period 2009-2019. Six and nine studies were included respectively. Quantitative pooling of data was not possible due to the heterogeneity of the studies. Oral mucositis (OM), nausea/vomiting, diarrhoea and dysgeusia were the most frequently reported nutritional problems. Cryotherapy and laser therapy seem to be effective in the prevention and treatment of OM. Recommendations for or against the use of mouth rinses and light therapy in the treatment of OM cannot be made, as too few studies have been conducted in this area. The evidence for non-pharmacological treatment options in the case of nausea/vomiting and diarrhoea is rather limited. No study was identified with regard to treatment of dysgeusia. Nutrition in HSCT patients has not yet been studied to a satisfactory extent. There is an urgent need for high-quality studies to be conducted in this area to optimise the care of patients undergoing haematopoietic stem cell transplantation.


Role of orally available antagonists of factor Xa in the treatment and prevention of thromboembolic disease: focus on rivaroxaban.
Interpatient variability in the safety and efficacy of oral anticoagulation with warfarin presents several challenges to clinicians, thus underscoring the emergent need for new orally available anticoagulants with predictable pharmacokinetic and pharmacodynamic profiles and ability to target circulating clotting factors. Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome. At doses used in phase 2 and 3 clinical trials, rivaroxaban and apixaban demonstrated a predictable onset of effect, maximal plasma concentration, and half-life that was unaffected by age, renal, or hepatic disease. In clinical trials for the treatment and prevention of venous thromboembolism, rivaroxaban and apixaban produced equivalent or superior reductions in the development or progression of venous thromboembolism compared with either low molecular weight heparin or warfarin. Trials comparing the efficacy of rivaroxaban or apixaban to standard therapy for stroke prophylaxis in patients with atrial fibrillation are in process. Rivaroxaban, the sentinel compound in this class, is already approved in the European Union and Canada. It is likely to be approved for use in the United States in 2010.


Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome.
Previous qualitative volumetric assessment of lateral ventricular enlargement in chronic fatigue syndrome (CFS) has provided evidence for subtle structural changes in the brains of some individuals with CFS. The aim of this pilot study was to determine whether a more sensitive quantitative assessment of the lateral ventricular system would support the previous qualitative findings. In this study, we compared the total lateral ventricular volume, as well as the right and left hemisphere subcomponents in 28 participants with CFS and 15 controls. Ventricular volumes in the CFS group were larger than in control groups, a difference that approached statistical significance. Group differences in ventricular asymmetry were not observed. The results of this study provide further evidence of subtle pathophysiological changes in the brains of participants with CFS.


Transitioning to thoracic endovascular repair: a single institution's analysis of the management of blunt aortic injury.
Over the past 15 years, there has been a rapid transformation in the way blunt aortic injuries (BAIs) are managed shifting from open thoracotomies to thoracic endovascular repairs (TEVAR). As a result of this change, we sought to describe our experience with open and endovascular repairs through a retrospective analysis of all trauma patients admitted with BAI to our Level I trauma center from 2002 to 2011. Demographic data, type of repair, complications, length of stay (LOS) data, and mortality were identified. No difference was noted in age, sex, Injury Severity Score, or Glasgow Coma Scale score between the two groups. There were also no differences in the number of acute complications or mortality. Intensive care unit (ICU) LOS was significantly shorter in the TEVAR group (20 vs 9 days, P < 0.05). Additionally, there was a trend toward shorter hospital LOS (28 vs 18 days, P = 0.07) and ventilator length of stay (12 vs 5 days, P = 0.171). In summary, endovascular repair of BAI is safe and has no increased rate of acute complications or mortality. ICU LOS is much shorter with TEVAR, and there was a trend toward shorter ventilator and hospital LOS, all of which may result in decreased cost. Still, more needs to be learned about potential long-term complications.


[A prospective study of risk factors in pregnant women with abnormal glucose metabolism].
To evaluate the risk factors for gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). A prospective case-control study was performed in 85 women with GDM, 63 cases with GIGT and 125 cases as control recruited from Feb 2004 to Aug 2004 in Peking University First Hospital. Univariate analysis and multivariate logistic regression were used to identify risk factors of GDM and GIGT. (1) The mean age, and body mass index (BMI) before pregnancy and larger maternal weight gains during pregnancy were significantly different between GDM/GIGT and control group (P < 0.05). (2) More intakes of fruits and carbohydrate per day increased the incidence of GDM and GIGT (P < 0.05). (3) There was a higher proportion of women with family history of diabetes among the GDM (42.2%) and GIGT (36.5%) compared with control group (19.2%). Irregular menses (16.5%, 23.8%), and polycystic ovary syndrome (PCOS) (5.9%, 3.2%) were more prevalent in the GDM, GIGT groups versus control subjects (6.4%, 0). The incidence of vulvovaginal candidiasis (VVC) was significantly higher in pregnant women with GDM and GIGT (15.3% and 17.4%) than in control group (7.2%). (4) Multivariate logistic regression showed that age, irregular menses, BMI before pregnancy, history of spontaneous abortion, educational level and VVC all were independent factors for GDM or GIGT. Maternal age, irregular menses, obesity before gestation, rapid weight gains during pregnancy, history of spontaneous abortion as well as VVC are independent risk factors for GDM or GIGT. PCOS and family history of diabetes increase the incidence of GDM and GIGT but these are not independent risk factors for GDM and GIGT.


Digital Mammography and Digital Breast Tomosynthesis.
Breast imaging technology has advanced significantly from the 1930s until the present. American women have a 1 in 8 chance of developing breast cancer. Mammography has been proven in multiple clinical trials to reduce breast cancer mortality. Although a mainstay of breast imaging and improved from film-screen mammography, digital mammography is not a perfect examination. Overlapping obscuring breast tissue limits mammographic interpretation. Breast digital tomosynthesis reduces and/or eliminates overlapping obscuring breast tissue. Although there are some disadvantages with digital breast tomosynthesis, this relatively lost-cost technology may be used effectively in the screening and diagnostic settings.


Anti-inflammatory and free radical scavenging activity of Ricinus communis root extract.
Anti-inflammatory and free radical scavenging activities of the methanolic extract of Ricinus communis (RCM) (Euphorbiaceae) Linn. root was studied in Wistar albino rats. The methanolic extract at doses 250 and 500 mg/kg p.o. exhibited significant (P<0.001) anti-inflammatory activity in carrageenan-induced hind paw edema model. The extract at the dose of 500 mg/kg p.o. also exhibited significant (P<0.001) anti-inflammatory activity in cotton pellet granuloma model. The methanolic extract showed significant free radical scavenging activity by inhibiting lipid peroxidation initiated by carbon tetrachloride and ferrous sulphate in rat liver and kidney homogenates. The extract enhanced free radical scavenging activity of stable radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH*), nitric oxide and hydroxyl radical in in vitro assay methods. The results of the study indicate that the methanolic extract of Ricinus communis root possess significant anti-inflammatory activity in acute and chronic inflammatory models in rats. The observed pharmacological activity may be due to the presence of phytochemicals like flavonoids, alkaloids and tannins present in the plant extract with various biological activities.


Photothermoelectric SnTe Photodetector with Broad Spectral Response and High On/Off Ratio.
A broadband photodetector with high performance is highly desirable for the optoelectric and sensing application. Herein, we report a "photo-thermo-electric" (PTE) detector based on an ultrathin SnTe film. The (001)-oriented SnTe films with the wafer size scale are epitaxially grown on the surface of sodium chloride crystals by a scalable sputtering method. Due to the giant PTE effect under laser spot excitation on the asymmetric position between two terminals, a built-in electrical field is produced to drive bulk carriers for a self-powered photodetector, leading to a broad spectral response in the wavelength range from 404 nm to 10.6 μm far beyond the limitation of the energy band gap. Significantly, the photodetector displays a high on/off photoswitching ratio of over 105 with a suppressed dark current, which is 4-5 orders of magnitude higher than that of other reported SnTe-based detectors. Under zero external bias, the device yields the highest detectivity of ∼1.3 × 1010 cm Hz1/2 W-1 with a corresponding responsivity of ∼3.9 mA W-1 and short rising/falling times of ∼78/84 ms. Furthermore, the photodetector transferred onto the flexible template exhibits excellent mechanical flexibility over 300 bending cycles. These findings offer feasible strategies toward designing and developing low-power-consumption wearable optoelectronics with competitive performance.


The distribution of catalase activity, isozyme protein, and transcript in the tissues of the developing maize seedling.
The catalase activity, CAT-2 and CAT-3 isozyme protein levels, and the steady-state mRNA levels for each of the three catalase genes were determined in the scutellum, root, epicotyl, and leaf of the developing maize (Zea mays L.) seedling. Catalase activity was highest in the scutellum, with 10-fold lower enzyme activity in the leaf and epicotyl. Very low levels of catalase activity were found in the root. The highest levels of CAT-2 protein were found in the scutellum, with about 10-fold lower levels in the green leaf. CAT-2 protein was present in trace amounts early in root development and no CAT-2 protein was detected in the epicotyl. Shortly after germination, CAT-3 protein was present at high levels in both the epicotyl and green leaf. With development, the amount of CAT-3 protein decreased slowly in the epicotyl and rapidly in the green leaf. Low levels of this isozyme were detected in the scutellum and root. The Cat1 transcript accumulated to low levels in all four tissues during the 14 day developmental period. High levels of the Cat2 transcript were found in the scutellum, with moderate levels of the mRNA in the green leaf. The Cat2 transcript levels were very low in the root and epicotyl. While the Cat3 mRNA level in the scutellum was low, high levels of the Cat3 transcript were detected in the root, epicotyl, and leaf. There was a positive correlation between the accumulation of a catalase isozyme and its transcript, indicating that the tissue specificity of maize catalase gene expression was regulated pretranslationally.


The RhoGAP domain of CYK-4 has an essential role in RhoA activation.
Cytokinesis in animal cells is mediated by a cortical actomyosin-based contractile ring. The GTPase RhoA is a critical regulator of this process as it activates both nonmuscle myosin and a nucleator of actin filaments [1]. The site at which active RhoA and its effectors accumulate is controlled by the microtubule-based spindle during anaphase [2]. ECT-2, the guanine nucleotide exchange factor (GEF) that activates RhoA during cytokinesis, is regulated by phosphorylation and subcellular localization [3-5]. ECT2 localization depends on interactions with CYK-4/MgcRacGAP, a Rho GTPase-activating protein (GAP) domain containing protein [5, 6]. Here we show that, contrary to expectations, the Rho GTPase-activating protein (GAP) domain of CYK-4 promotes activation of RhoA during cytokinesis. Furthermore, we show that the primary phenotype caused by mutations in the GAP domain of CYK-4 is not caused by ectopic activation of CED-10/Rac1 and ARX-2/Arp2. However, inhibition of CED-10/Rac1 and ARX-2/Arp2 facilitates ingression of weak cleavage furrows. These results demonstrate that a GAP domain can contribute to activation of a small GTPase. Furthermore, cleavage furrow ingression is sensitive to the balance of contractile forces and cortical tension.


In situ observations of water production and distribution in an operating H2/O2 PEM fuel cell assembly using 1H NMR microscopy.
Proton NMR imaging was used to investigate in situ the distribution of water in a polymer electrolyte membrane fuel cell operating on H2 and O2. In a single experiment, water was monitored in the gas flow channels, the membrane electrode assembly, and in the membrane surrounding the catalysts. Radial gradient diffusion removes water from the catalysts into the surrounding membrane. This research demonstrates the strength of 1H NMR microscopy as an aid for designing fuel cells to optimize water management.


Confidence intervals for population projections based on Monte Carlo methods.
"This paper presents an approach of constructing confidence intervals by means of Monte Carlo simulation. This technique attempts to incorporate the uncertainty involved in projecting human populations by letting the fertility and net immigration rates vary as a random variable with a specific distribution. Since fertility and migration are by far the most volatile, and therefore, the most critical components to population forecasting, this technique has the potential of accounting for this uncertainty, if the subjective distributions are specified with enough care. Considering the results of the model for the U.S. in 2082, for example, it is shown that the population will number between 255 million and 355 million with a probability of 90 percent."


Manure storage operations mitigate nutrient losses and their products can sustain soil fertility and enhance wheat productivity.
Livestock manure is a valuable source of nutrients for plants. However, poor handling practices during storage resulted in nutrient losses from the manure and decrement in its nitrogen (N) fertilizer value. We explored the influence of divergent storage methods on manure chemical composition, carbon (C) and N losses to the environment as well as fertilizer value of storage products after their application to the wheat. Fresh buffalo manure (FM) was subjected to different storage operations for a period of ∼6 months, (i) fermentation by covering with a plastic sheet (CM) (ii) placed under the roof (RM) (iii) heap was unturned (SM) to remain stacked at an open space and (iv) manure heap turned monthly (TM) to make compost. During storage, 8, 24, 45 and 46% of the initial Ntotal was lost from CM, RM, SM, and TM, respectively. The respective C losses from these treatments were 16, 34, 47 and 44% of the initial C content. After stored manures application to the wheat crop, mineral N in the soil remained 27% higher in CM (14.1 vs. 11.1 kg ha-1) and 3% (10.8 vs. 11.1 kg ha-1) lower in SM compared to FM treatment. In contrast, microbial biomass C and N was 35 (509 vs.782 mg C kg-1 soil) and 25% (278 vs.370 mg N kg-1 soil) lower in CM than FM treatment, respectively indicating lower N immobilization of CM in the soil. These findings could result in the highest grain yield (5166 kg ha-1) and N uptake (117 kg ha-1) in CM and the lowest in SM treatments (3105 and 61 kg ha-1, respectively). Similarly, wheat crop recovered 44, 15 and 13% N from CM, TM and SM, respectively. Hence, management operations play a critical role in conserving N during storage phase and after stored manure application to the field. Among the studied operations, storing animal manure under an impermeable plastic sheet is a much better and cheaper option for decreasing N losses during storage and improving wheat yield when incorporated into the soil. Therefore, by adopting this manure storage technique, farmers can improve the agro-environmental value of animal manure in Pakistan.


[Diagnostic arthroscopy of the wrist in adults and children with subsequent single-stage surgical procedures].
Wrist arthroscopy today still faces the problem of being much to often diagnostic only. In addition, if the diagnosis requires a larger operation to follow, it can rarely be performed in the same session. Above all the special positioning makes a second session necessary. A new technique of wrist arthroscopy established in the University Clinic of Basel, Switzerland, allows a conventional positioning and thus a secondary surgical procedure in the same session. In a prospective clinical two-centre study, we aim to answer questions about general feasibility and possible complications due to the multiple compartment anatomy in adults and children. In the two centres, University Clinic for Hand Surgery Basel, Switzerland and Orthopaedic Clinic IPVZ Hospital Bulovka, Czech Republic, we perform the new technique of wrist arthroscopy without distraction. Conventional 2.4 mm arthroscope and the III/IV, VI/R and MCU--approaches were used in adult patients (n = 147) and children (n = 10). High pressures up to 150 mm Hg of Ringer's lactate solution replaced the traction, but leaving the wrist freely movable and in a comfortable horizontal position. If indicated by the diagnostic arthroscopy, an open operation on the wrist was performed immediately. A standardised regimen of previously arranged clinical controls was followed. Out of 157 wrist arthroscopies performed in the two clinics, 32 had an arthrotomy or another surgical procedure to follow in the same session. The mean duration of the diagnostic arthroscopy was 34 minutes. There were no arthroscopy related complications. Also in children, the arthroscopy gave the sufficient information about wrist anatomy and it was possible to continue with the surgical procedure in the same session. According the literature reports, the arthrotomy does not follow the wrist arthroscopy using distraction, because the complicated positioning of the extremity. Wrist arthroscopy without distraction is a new technique, previously published by first author, and enables arthrotomy of the wrist in the same session, and was not previously published. Also arthroscopy of the wrist in the childhood was not published up to now. In our study we have proven the feasibility of an arthrotomy or another surgical procedure to follow an arthroscopy on the wrist, all despite the special anatomical situation and the high intraarticular fluid pressure. We conclude the overall cost to be reduced and the patient's comfort improved. The method of the wrist arthroscopy without distraction can be used also in the childhood.


[99mTc-pingyangmycin imaging to assess treatment response of patients with lung cancer].
The aim of this study was to investigate the possibility of functional imaging for the assessing of treatment response in patients with lung cancer. Thirty one patients were studied by 99mTc-Pingyangmycin (PYM) imaging. A region-of-interest technique was used in planar scan and the retention index (RI) was obtained to evaluate quantitatively the degree of 99mTc-PYM retention in the lesions. It was found that the RI was significant difference between responder (-5.01 +/- 4.97, -6.78 +/- 3.05) and nonresponder (4.38 +/- 2.13, 15.25 +/- 5.92, P < 0.05, P < 0.001) to chemotherapy or radiotherapy. Significant difference was also seen between patients with stable disease (-6.07 +/- 8.45) and those with disease progression (12.66 +/- 5.23, P < 0.01) after surgical treatment. Repeated examinations showed good correlation between difference of pretreatment and posttreatment RI and reduction of tumor volume (r = 0.8959, P < 0.01). Therefore, RI can be taken as a predictive index in assessing tumor response to treatment and in monitoring lung cancer patients surgically treated.


Cavitation in heavy water and other liquids.
We report on measurements of the cavitation pressure in several liquids subjected to tension in an acoustic wave and compare the results to classical nucleation theory (CNT). This study is motivated by the sizable discrepancy between the acoustic cavitation threshold measured in water and the value predicted by CNT. We find that the same discrepancy is present for heavy water, whereas the agreement is better for ethanol and heptane and intermediate in the case of dimethyl sulfoxide. It is well-known that water is an anomalous liquid, a consequence of its hydrogen-bonded network. The other liquids studied represent very different molecular interactions. Our results indicate that the cavitation threshold approaches the prediction of CNT as the surface tension gets smaller. Conversely, this raises the question of the validity of a simple theory such as CNT to account for high surface tension liquids and suggests that an appropriate microscopic model of such liquids may be necessary to correctly predict the cavitation threshold.


Inhaled corticosteroids and leukotriene modifiers in the acute treatment of asthma exacerbations.
Asthma exacerbation has a considerable impact on patients' quality of life and constitutes a challenging condition for primary health-care providers. Severe exacerbations are also an important cause of hospital admissions and require high costs. Despite this, a widely accepted definition is still lacking; etiologic and pathogenetic mechanisms are still incompletely defined. Although the efficacy of inhaled corticosteroids (ICS) and leukotriene modifiers in preventing mild to moderate asthma exacerbation is well recognized, their role within the context of an asthma action plan in general practice and in home-based early intervention for acute exacerbations is still controversial. Although systemic corticosteroids (CS) are standard care for severe exacerbation in the emergency department's (ED) management of asthma, published evidence suggests that high doses of ICS may be beneficial in the ED. The additive benefit of ICS when used with systemic CS is still debated. Data on leukotriene modifiers in the management of asthma exacerbation are limited. However, therapeutic strategies of this emergency including ICS and leukotriene modifiers seem logical and may be suitable, at least in certain patient groups. The availability of different drugs, active on different targets, can potentially contribute to a better management of asthma exacerbations.


[Bing-Neel syndrome successfully treated with tirabrutinib].
Bing-Neel syndrome (BNS) is a rare disease manifestation of Waldenström's macroglobulinemia characterized by abnormal lymphoplasmacytoid cells infiltration of the central nervous system. In September 2019, a 46-year-old man presented to a previous hospital with hand tremors, nausea, and dysuria. Demyelination of cerebral white matter and the spinal cord was discovered using MRI. Steroid pulse therapy was used to treat inflammatory demyelinating disease, and it provided temporary relief, but the symptoms returned when the steroids were stopped. He was referred to our hospital in June 2020, for further evaluation with the possibility of hematological malignancy. BNS was diagnosed based on the presence of abnormal lymphoplasmacytoid cells in the bone marrow and cerebrospinal fluid (CSF), as well as the presence of the MYD88L265P mutation in the CSF specimen. In July 2020, BR (bendamustine, rituximab) therapy was administered, but it was ineffective. Oral administration of tirabrutinib, which was recently approved for WM, began in August 2020. He has achieved long-term remission and steroid withdrawal, with no notable side effects. This is the second report of successful treatment of BNS with tirabrutinib. More research is needed to confirm tirabrutinib's efficacy in the treatment of BNS.


A 5-year clinical evaluation of the effectiveness of a fissure sealant in mentally retarded Canadian children.
The occlusal fissures of 812 permanent and primary posterior teeth were sealed with an ultraviolet polymerisable resin. A half mouth technique was used to evaluate the effectiveness of the sealant in the prevention of fissure caries. At the end of 5 years 19.3% of 409 teeth in 103 children had the sealant completely intact and fissures were partially sealed in 20.8%. Retention was greatest in the mandibular pre-molars. The decay rate was less than half in the treated teeth compared to the control teeth. The net gain was 62 teeth and the percent effectiveness was 57.9%. Thus there was still a highly significant effect of a single application of the fissure sealant after 5 years. Simple cost benefit calculations indicate that the technique is not suitable as a public health measure but has merit for mentally retarded persons and in private practice situations.


Identifying Barriers to Initiating Minimal Enteral Feedings in Very Low-Birth-Weight Infants: A Mixed Methods Approach.
This study aims to elicit physician and nursing perceptions about initiation of minimal enteral feedings (MEF) in very low-birth-weight (VLBW) infants. A three-phase, mixed methods study including a quantitative chart review of 37 VLBW infants, followed by 26 qualitative observations of morning rounds, 26 interviews of neonatal intensive care unit (NICU) medical team members, tailored interventions based on the identified barriers to MEF, and finally a postintervention chart audit of 50 VLBW infants. The main barriers to initiation of MEF were failure to appreciate the differences between the goals of MEF versus nutritive feedings, inconsistent definition of "sick" infant, indomethacin for intraventricular hemorrhage prophylaxis, awaiting mother's own milk, complicated feeding protocols/algorithms for feeding intolerance, and lack of buy-in from nurses/nurse practitioners. The compliance with early initiation of MEF per the feeding guidelines rose from 25 to 92% after our interventions. Understanding the complex interplay of provider, system and patient-based factors that interfere with initiation of MEF may enable NICUs to develop consensus guidelines and targeted interventions and to achieve timely initiation of nonnutritive feedings.


Identification of vaccine human papillomavirus genotypes in squamous intraepithelial lesions (CIN2-3).
To identify the prevalence of human papillomavirus vaccine genotypes and non-vaccine genotypes implicated in the appearance of cervical intraepithelial neoplasia (CIN2-3). Prospective study of 519 women with abnormal cytology. All the women underwent a second Papanicolaou test, cervicovaginal sampling for type-specific HPV detection and colposcopy, and women with abnormal colposcopy results were referred to biopsy. Pearson's chi-square test was used for statistical analysis. HPV was detected in 340 patients (65.5%), and in 125 (24%) more than one HPV genotype was present. We selected 206 patients with CIN2 or CIN3 confirmed by biopsy. In 88 (42.7%) of these patients, HPV types 16 and 18 were detected, but only 58 (28.2%) without co-infection by other high-risk or probable high-risk HPV types. In 115 (55.8%) women diagnosed with CIN2 or CIN3 high-risk or probable high-risk HPV types other than 16 or 18 were found. High-risk and/or probable high-risk HPV genotypes not included in the vaccine were isolated in this study more frequently than 16 or 18, and this difference was statistically significant (p=0.047). Of the 206 women diagnosed with CIN2 or CIN3, 19 tested negative for HPV and 14 tested positive for low-risk HPV types. Only 28.2% of women with CIN2 or CIN3 confirmed by biopsy were infected exclusively by HPV type 16 or 18, a finding that places in doubt the degree of protection afforded by HPV vaccination.


Biosensors for the Detection of Bacillus anthracis.
Bacillus anthracis, present in two forms of vegetative cells and spores, is a pathogen that infects humans through contact with infected animals or contaminated animal products and is also maliciously used in terrorist acts. Therefore, a rapid and sensitive test for B. anthracis is necessary but challenging. The challenge comes from the following aspects: an accurate distinction of B. anthracis from other Bacillus species due to their high genomic similarity and the horizontal gene transfer between Bacillus members; direct detection of the B. anthracis spores without damaging them for component extraction to avoid the risk of spore atomization; and the rapid detections of B. anthracis in complex samples, such as soil and suspicious powders, without sample pretreatments and expensive large-scale equipment. Although culturing B. anthracis from samples is the conventional method for the detection of B. anthracis, it is time-consuming and the detection results would not be easy to interpret because many Bacillus species share similar phenotypic features such as a lack of motility and hemolysis, resistance to gamma phages, and so on. Intensive and extensive effort has been expended to develop reliable detection technologies, among which biosensors exhibit comprehensive advantages in terms of sensitivity, specificity, and portability. Here, we briefly review the research progress, providing highlights of the latest achievements and our own practice and experience. The contents can be summarized in three aspects: the discovery of detection targets, including genes, toxins, and other components; the creation of molecular recognition elements, such as monoclonal antibodies, single-chain antibody fragments, specific peptides, and aptamers; and the design and construction of biosensing systems by the integration of appropriate molecular recognition elements and transducer devices. These sensor devices have their own characteristics and different principles. For example, the surface plasmon resonance biosensor and quartz crystal microbalance biosensor are very sensitive, while the multiplex PCR-on-a-chip can detect multitargets. Biosensors for direct spore detection are highly recommended because they are not only fast but also avoid contamination from aerosol-containing spores. The introduction of nanotechnology has significantly improved the performance of biosensors. Superparamagnetic nanoparticles and phage-displayed gold nanoparticle ligand peptides have made the results of spore detection visible to the naked eye. Because of space constraints, many advanced biosensors for B. anthracis are not described in detail but are cited as references. Although biosensors provide a variety of options for various application scenarios, the challenges have not been fully addressed, which leaves room for the development of more advanced and practical B. anthracis detection means.


Invasion of visual cortex by the auditory system in the naturally blind mole rat.
Previously we have shown that the dorsal lateral geniculate body (LGB), which is strictly visual in sighted mammals, receives a strong auditory input in the naturally blind mole rat (Spalax ehrenbergi). Here we show with the 2-deoxyglucose technique and with single-unit recordings that in this species the initially non-degenerated visual cortex, as defined by its connection with LGB, is also activated by the auditory modality. These findings suggest that cross-modal compensation may occur as a natural consequence of the degeneration of a sense organ.


Ultrastructural changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy.
Diabetic nephropathy is invariably associated with proteinuria. To delineate the mechanism(s) of proteinuria in diabetic nephropathy, ultrastructural changes of the glomerular basement membranes (GBMs) were studied by high resolution scanning and immunoelectron microscopy. Acellular glomeruli from diabetic and age-matched control human subjects were prepared by detergent method and subjected to conductive staining, the technique in which the tissues are impregnated with metals rather than surface-coated with metallic alloys for visualization by electron microscopy. Subsequent to conductive staining, the tissues were examined by in-lens field emission scanning electron microscopy. Thirty glomeruli, each from the control and diabetic groups, were examined by scanning microscopy. In diabetic GBMs, a loose meshwork structure consisting of numerous pores of approximately 8 nm in diameter and distinct strands was observed. In contrast, meshwork structure was not readily discernible in controls and a few pores were observed. Five glomerular capillary loops, each from control and diabetic groups, were examined by immunoelectron microscopy. In controls, heparan sulfate-proteoglycan was localized in the lamina rara interna and externa, and type-IV collagen was distributed throughout the whole width of the GBM. In diabetic GBMs, a relative loss of staining of heparan sulfate-proteoglycan, both in the lamina rara interna and externa of the GBM, was observed. Type IV collagen was distributed in all layers of the thickened GBM, and the absolute number of the immunogold particles was increased. However, immunogold particle density of type IV collagen per unit area was decreased as compared with the control. These ultrastructural and immunoelectron microscopic changes in the GBM may explain the loss of charge as well as size selectivities of the glomerulus, as observed in diabetic nephropathy associated with proteinuria.


Investigation of photodynamic therapy optimization for port wine stain using modulation of photosensitizer administration methods.
To raise photosensitizer concentration level during the photodynamic therapy process, two new methods of photosensitizer administration were investigated. The first method involves the slow intravenous injection of photosensitizer throughout the first 15 min of irradiation, and the second method involves 30 min fomentation before photosensitizer injection and irradiation. The fluorescence spectra of port wine stain skin were monitored and the therapeutic effect correlated index was calculated with a previously published spectral algorithm. Thirty cases were divided into group A (slow injection of photosensitizer during the first 15 min), group B (fomentation), and group C (control group, traditional injection method), with 10 cases in each group. To analyze the effect of these two new methods, the change of therapeutic effect correlated index values of two photodynamic therapy sessions for each patient were calculated, and the photodynamic therapy outcome was compared. The results showed that the change of therapeutic effect correlated index in group A was slightly more remarkable than that in the control group. The change of therapeutic effect correlated index in group B was similar to that in the control group. Slow injection of photosensitizer during photodynamic therapy has a potential to increase photosensitizer concentration level during photodynamic therapy. However, fomentation before photodynamic therapy has no such potential. There is a need for new methods to be attempted.


Do Longer Surgical Procedures Result in Greater Contamination of Surgeons' Hands?
A surgical site infection is a substantial cause of complications in patients. Different methods are being used to decrease surgical site infections; however, these infections still can cause complications, especially in patients undergoing longer operations (> 3 hours). There is evidence that the efficacy of the scrubbing material fades after 3 hours. However, we do not know the longevity of hand cleanliness after application of scrubbing materials in a long operation. It can be postulated that if the surgeon's scrubbed hands are recolonized after a certain time, they may serve as a progressive source of contamination during surgery. We asked: (1) Is there a correlation between surgical duration and hand contamination at the end of surgery? (2) At what point during surgery does hand contamination reach or exceed prescrub levels? Three spine surgeons using the same scrubbing technique and materials consisting of chlorhexidine gluconate 1% solution and ethyl alcohol 61% w/w were enrolled in our study. Between December 2014 and April 2015, spine procedures of 3 hours or more, which were the first case of the day, were selected for this study (20 cases). Cases in which glove changing occurred (perforations, reprepping, and redraping) or cultures obtained after scrubbing were positive (indicative of insufficient hand sanitization) were excluded (0% of cases). Twenty cases (100% enrollment) were analyzed. Surgeons' hands were swabbed with sterile cotton tip applicators and 5 mL sterile phosphate-buffered saline before hand scrubbing (prescrub), immediately after hand scrubbing (postscrub), and immediately after surgery (postoperative). Results were reported in colony-forming units per milliliter. The correlation between duration of surgery and hand recontamination was tested by regression analysis of time versus colony-forming units per milliliter. Receiver-operating characteristic curve tested the cutoff point, where recontamination occurred. With a longer duration of surgery, more colony-forming units are recovered from gloved hands at the end of surgery (R = 0.94, R(2) = 0.89, p = 0.005). The receiver-operating characteristic curve suggested that 5 hours is the cutoff point for hand recolonization. At 5 hours, contamination reached or exceeded prescrub levels (area under the curve, 0.66; 95% CI, 0.23-1.0), whereas before 5 hours, there was no contamination detected at the end of surgery. Our results show that duration of surgery correlates with hand recontamination and at 5 hours, recolonization of a surgeon's hands become detectable. Recolonization may have started even earlier than 5 hours. However, these levels are not detectable in the laboratory at earlier times. Based on this pilot study, rescrubbing is highly recommended before the fifth hour of an operation, ideally at some point between the fourth and fifth hours. We also recommend the surgical site infection rates in operations using rescrubbing should be compared with those from surgeries with just the conventional single-scrubbing technique, in a randomized controlled trial, to determine the effectiveness of this novel rescrubbing method.


Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.
In previous reports, nude mice have demonstrated residual immunoreactivity against xenografts. Severe combined immunodeficient (SCID) mice lack functional T- and B-cells. These animals are expected to be better hosts in which to perform preclinical studies on human tumors. The purpose of this study is to quantitate the advantage of SCID mice over nude mice in terms of transplantability of human and murine tumors and the importance of residual immunity in SCID mice. The transplantation assays are described by an assay based on the number of tumor cells required to transplant tumor into 50% of recipients (TD50). Seven human tumors of different histology and four murine tumor cell lines were used. Serial 2-10-fold dilutions of cells were injected (0.1 ml) into the flanks of normal and whole-body irradiated WBI nude and SCID mice. The results showed that in 6 of 6 human tumor cell lines studied, TD50S for SCID mice were 2.4 to 200 times lower than that of nude mice (significant in 5 cell lines). In contrast, in 2 of 3 murine tumors, TD50S in WBI SCID mice were significantly higher than that found in nude mice. When SCID and nude mice received WBI, TD50S were lower than those of nonirradiated animals in 5 of 5 xenografts (significant in 2 cell lines for nude mice and in 5 cell lines for SCID mice). We concluded that WBI SCID mice are significantly better recipients of human tumor xenografts than nude mice. There is a factor of 10-1625 gain in TD50S in favor of the WBI SCID mice when compared to nonirradiated nude mice. WBI has, however, an important effect on SCID mice which may suggest a detectable residual immunoreactivity, perhaps due to natural killer cells. These data demonstrate that WBI SCID mice are better models for human tumor transplantation that nude mice and, although WBI at 6 Gy suppressed significantly the immune system of nude mice, a certain level of immunoreactivity against xenografts is still maintained.


Cup-and-spill gastric deformity following Hassab's procedure for oesophageal varices: case report.
Hassab's operation for selected case of oesophageal varices is believed by many workers to be a very satisfactory procedure. Various complications following this procedure have been reported, but none has reported a case of Cup-and-Spill gastric deformity following this operation. We present such a complication following this procedure on a senior medical colleague with oesophageal varices resulting from a subclinical or previously undiagnosed hepatitis resulting in liver fibrosis. He responded fairly well to conservative treatment and small feed at frequent interval.


Decree No. 88-737 setting the duties of the Minister of Social Affairs and concerning the reorganization of the Ministry, 31 August 1988.
This Decree sets forth the duties of the Minister of Social Affairs of the Ivory Coast. These include, among others, 1) organizing the social protection of the family, childhood, youth, and persons who are handicapped, maladjusted, and disadvantaged; 2) organizing, encouraging, and sensitizing individuals, families, and communities with a view towards promoting their psychological well-being, health, and social development; 3) studying and programming all new preventative or curative activities, leading to the betterment of individuals, families, and groups; 4) bringing assistance to individuals, families, and groups whose social situation requires state help; and 5) organizing the social protection of workers and their families. Among the departments of the Ministry of Social Affairs is the Directorate of Social Development, which is to create and ensure the application of national programs of family protection and social promotion of the population, through family and preschool education. Further provisions of the Decree describe the other departments and personnel of the Ministry.


Proteomics of Cryptococcus neoformans: From the Lab to the Clinic.
Fungal pathogens cause an array of diseases by targeting both immunocompromised and immunocompetent hosts. Fungi overcome our current arsenal of antifungals through the emergence and evolution of resistance. In particular, the human fungal pathogen, Cryptococcus neoformans is found ubiquitously within the environment and causes severe disease in immunocompromised individuals around the globe with limited treatment options available. To uncover fundamental knowledge about this fungal pathogen, as well as investigate new detection and treatment strategies, mass spectrometry-based proteomics provides a plethora of tools and applications, as well as bioinformatics platforms. In this review, we highlight proteomics approaches within the laboratory to investigate changes in the cellular proteome, secretome, and extracellular vesicles. We also explore regulation by post-translational modifications and the impact of protein-protein interactions. Further, we present the development and comprehensive assessment of murine models of cryptococcal infection, which provide valuable tools to define the dynamic relationship between the host and pathogen during disease. Finally, we explore recent quantitative proteomics studies that begin to extrapolate the findings from the bench to the clinic for improved methods of fungal detection and monitoring. Such studies support a framework for personalized medical approaches to eradicate diseases caused by C. neoformans.