Effects of medium acetate on cellular volume in rabbit renal cortical slices.
Slices of rabbit renal cortex were incubated at 25 degrees C in media in which acetate replaced chloride. There was gross cellular swelling in isosmotic 132 mM-acetate medium, and this swelling was unique in that, with a normal medium potassium concentration, it was accompanied by a substantial increase in cellular potassium content. This accumulation of potassium, but not the cellular swelling, was dependent upon metabolism and inhibited by ouabain. This accumulation of potassium was not dependent upon the cellular swelling. It also occurred in a hyperosmotic acetate medium in which swelling was minimized. In isosmotic media, the cellular swelling was proportional to medium acetate concentration and was also affected markedly by medium pH, being greatest at an initial medium pH of 7.1 and least at pH 7.7. The swelling was reversed and cellular composition restored when tissue was re-incubated in NaCl medium. Ouabain (10(-3)M) largely prevented this recovery in volume. The results are consistent with plasma-membrane-based theories, on the assumption that membranes are much more permeable to undissociated acetic acid than they are to the acetate ion. They are inconsistent with the expectations of an alternative hypothesis (the association--induction hypothesis) which ascribes the maintenance of cellular composition to properties of cellular proteins and cellular water rather than to those of the plasma membrane. The results do not favour the suggestion that cellular swelling itself results in irreversible cellular damage. The results are consistent with the hypothesis that the ouabain-inhibitable Na-K-ATPase plays a major role in the regulation of cellular volume. No alternative metabolically dependent volume regulating mechanism need be postulated to explain them.


Transcoronary ethanol ablation of the atrioventricular node in a young patient with tricuspid atresia.
Catheter ablation of AV conduction with radiofrequency energy can be challenging in the presence of structural abnormalities of the AV junction, either congenitally or after reconstructive surgery. We used transcoronary ethanol to ablate the AV node in a patient with classic tricuspid atresia and refractory intraatrial reentry tachycardia. This approach provides an alternative means of creating complete heart block with catheter-based techniques, when radiofrequency catheter ablation is technically impossible or ineffective.


Community assembly in epiphytic lichens in early stages of colonization.
Colonization studies may function as natural experiments and have the potential of addressing important questions about community assembly. We studied colonization for a guild of epiphytic lichens in a former treeless heathland area of 170 km2 in southwest Norway. We investigated if epiphytic lichen species richness and composition on aspen (Populus tremula) trees corresponded to a random draw of lichen individuals from the regional species pool. We compared lichen communities of isolated young (55-120 yr) and old (140-200 yr) forest patches in the heathland area to those of aspen forest in an adjacent reference area that has been forested for a long time. All thalli (lichen bodies) of 32 selected lichen species on trunks of aspen were recorded in 35 aspen sites. When data for each site category (young, old, and reference) were pooled, we found the species richness by rarefaction to be similar for reference sites and old sites, but significantly lower for young sites. The depauperated species richness of young sites was accompanied by a skew in species composition and absence of several species that were common in the reference sites. In contrast, genetic variation screened with neutral microsatellite markers in the lichen species Lobaria pulmonaria showed no significant differences between site categories. Our null hypothesis of a neutral species assembly in young sites corresponding to a random draw from the regional species pool was rejected, whereas an alternative hypothesis based on differences in colonization capacity among species was supported. The results indicate that for the habitat configuration in the heathland area (isolated patches constituting < 0.4% of the area) lichen communities may need a colonization time of 100-150 yr for species richness to level off, but given enough time, isolation will not affect species richness. We suggest that this contradiction to expectations from classical island equilibrium theory results from low extinction rates.


Mechanical behavior of glass ionomer cements as a function of loading condition and mixing procedure.
With a view to comparing conventional (CGIC) and resin-modified glass ionomer cements (RMGIC) in terms of mechanical properties, these materials were subjected to different loading conditions for evaluation. In addition, this study investigated the assumption that capsulated systems possess superior mechanical properties compared to the hand-mixed systems, owing to the former's better material homogeneity and a more precise adjustment of the powder-liquid ratio. In view of the aims of this study, the following mechanical properties were determined: strength and modulus of elasticity in flexural test, diametric tensile and compressive strengths, as well as variation of hardness and modulus of elasticity with depth. In all macroscopic strength tests, the RMGICs performed significantly better than the CGICs. In microhardness evaluation, the differences were levelled out. In particular, the mechanical properties of RMGICs were comparable to those of microfilled and packable composites. The effect of mixing was closely intertwined with material property. The tested CGICs performed better when they were hand-mixed, whereas RMGICs fared better in the capsulated form.


Genetic characterization of atypical enteropathogenic Escherichia coli isolates from ewes' milk, sheep farm environments, and humans by multilocus sequence typing and pulsed-field gel electrophoresis.
A collection of 81 isolates of enteropathogenic Escherichia coli (EPEC) was obtained from samples of bulk tank sheep milk (62 isolates), ovine feces (4 isolates), sheep farm environment (water, 4 isolates; air, 1 isolate), and human stool samples (9 isolates). The strains were considered atypical EPEC organisms, carrying the eae gene without harboring the pEAF plasmid. Multilocus sequence typing (MLST) was carried out with seven housekeeping genes and 19 sequence types (ST) were detected, with none of them having been previously reported for atypical EPEC. The most frequent ST included 41 strains isolated from milk and human stool samples. Genetic typing by pulsed-field gel electrophoresis (PFGE) resulted in 57 patterns which grouped in 24 clusters. Comparison of strains isolated from the different samples showed phylogenetic relationships between milk and human isolates and also between milk and water isolates. The results obtained show a possible risk for humans due to the presence of atypical EPEC in ewes' milk and suggest a transmission route for this emerging pathogen through contaminated water.


Burton's line in lead poisoning.
Lead poisoning in both its acute and chronic forms has been recognised since the second century BCE. Lead colic, anaemia, renal tubulopathies and motor neuropathies are well recognised. This paper sketches the early history and remembers the important contribution of Henry Burton, who described the gums to be bordered by a narrow leaden-blue line, about the one-twentieth part of an inch in width, whilst the substance of the gum apparently retained its ordinary colour and condition. The sign though inconstant, is still a valuable clinical clue.


Possible beneficial effects of health counseling, given less frequently than ordinary, on blood pressure.
This study was initiated to investigate the effects of health counseling under Total Health Promotion Plan (THP). The study populations consisted of 1,655 working men who had an initial THP-based counseling and a follow-up 3 yr later (the THP group; the counseling was given on a once-three year basis), and 1,655 age- and body mass index (BMI)-matched controls (working men who had no health counseling; the control group). In the THP group, systolic blood pressure (SBP) and the prevalence of excessive alcohol drinking were decreased, and nutritional score was improved, although BMI was increased. In contrast, SBP, BMI and the ratio of excessive drinkers were all increased in the controls. Multiple regression analysis of the THP group showed that the reduction in SBP was positively associated with the increase in maximal oxygen consumption (VO(2max)) and physical activity scores, as well as the decrease in BMI. In sub-group analyses of the THP group, VO(2max) and physical activity scores were increased, and BMI did not change in the sub-group with marked BP decrease. In the sub-group with marked BP increase, however, BMI was increased, and VO(2max) was decreased. The ratio of excessive drinkers was reduced only in the sub-group with marked BP decrease. The obese-hypertensive subjects in the THP group showed decreases in BMI and BP, and increases in VO(2max). Thus, these results appeared to suggest that health counseling given even at a low frequency of once in three years prevented the age-associated increase in BP through improvement of physical endurance, decrease in alcohol intake and reduction in body weight.


Effect of Variations in Stent Placement on Outcome of Endoluminal Stenting for Canine Tracheal Collapse.
The study's objective was to determine effects of relative size and placement location of endoluminal stents on incidence of complications and survival for canine tracheal collapse. Measurements were obtained on lateral radiographs before and after stenting to determine percent of the trachea occupied by the stent. These values were monitored over time and compared to complication rates and survival. Overall median survival time was 502 days. Six month survival rate was 78%, 1 yr survival was 60%, and 2 yr survival was 26%. Median percent of trachea occupied by the stent at initial placement was 79% (range, 41-93%). Percent of the trachea occupied by the stent at the time of placement did not significantly correlate to complication rate (0.397) or survival time (0.853). Incidence of serious complications was 37%, including granuloma formation, pneumonia, material failure, and stent migration. For patients experiencing serious complications, median survival was shorter, at 208 days, but was not significantly different from survival without serious complications. Within the margins of the data from this study, the proportion of the trachea occupied by the stent at the time of placement does not appear to impact incidence of complications or survival time in dogs with tracheal collapse.


Disorders of the distal radioulnar joint.
The distal radioulnar joint is responsible for stable forearm rotation. Injury to this joint can occur following a variety of mechanisms, including wrist fractures, ligamentous damage, or degenerative wear. Accurate diagnosis requires a clear understanding of the anatomy and mechanics of the ulnar aspect of the wrist. Injuries can be divided into three major categories for diagnostic purposes, and these include pain without joint instability, pain with joint instability, and joint arthritis. New advancements in imaging and surgical technique can allow for earlier detection of injuries, potentially preserving joint function. In this article, the authors review the pertinent anatomy, biomechanics, and major abnormality involving the distal radioulnar joint.


Delayed visual maturation and autism.
Three boys are described with a mixed developmental disorder, which so far appears to have a relatively good prognosis. Each boy presented in early infancy with visual unresponsiveness, which spontaneously resolved. This delayed visual maturation was accompanied or followed by severe autistic impairment, general developmental delay, hypotonia and clumsiness. Subsequent progress has been unexpectedly favourable, with striking improvements in language, play, social interest and social competence. Widespread, patchy delay in brain maturation could possibly account for this combination of delayed visual maturation and autism, with a good prognosis.


The effect of glucagon on airway resistance.
Nine subjects with obstructive airway disease took part in this double-blind study of the effect of glucagon in relieving bronchoconstriction compared with isoproterenol or isotonic saline. Drugs were administered via an in-line intermittent positive-pressure breathing unit. FEV1, MEF, PEF, and nitrogen washout data were evaluated. Ten minutes after administration of saline, mean FEV1 and MEF values were significantly reduced from baseline levels (P less than 0.05). Compared to saline, isoproterenol was followed by significantly increased FEV1 and MEF values (P less than 0.05) at both 10 and 30 minutes after medication, indicating reduction in bronchoconstriction. Although the 1-mg dose of glucagon was followed by a mean decrease in these parameters, this decrease was less than that seen after saline alone.


Effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain.
Objective To investigate the effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain. Methods Our study selected 100 clean grade healthy Sprague-Dawley adult male rats weighing 200 to 250 g. After establishment of a rat model of chronic constriction injury, these rats were divided into 10 groups (10 rats in each group): the normal control, sham operation, chronic constriction injury, normal saline, morphine, miR-223, NLRP3, miR-223 + morphine, NLRP3 + morphine, and miR-223 + NLRP3 + morphine groups. The real-time quantitative polymerase chain reaction assay, Western blotting, and enzyme-linked immunosorbent assay were used for detecting the mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, Interleukin (IL)-1β, and IL-18 in sections of lumbar spinal cord. Immunohistochemistry was applied for detecting the positive rates of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1β, and IL-18. Results The paw withdrawal threshold and percentage maximum possible effect (%MPE) were higher in chronic constriction injury group when compared with the normal control and sham operation groups. Behavioral tests showed that compared with the chronic constriction injury and normal saline groups, the morphine and miR-223 + morphine groups showed obvious analgesic effects. Expressions of miR-223 in the miR-223, miR-223 + morphine, and miR-223 + NLRP3 + morphine were significantly higher than those in the chronic constriction injury, normal saline, and morphine groups. Compared with chronic constriction injury, normal saline and morphine groups, the mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1β, and IL-18 were significantly decreased in the miR-223 and miR-223 + morphine groups, while mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1β, and IL-18 were significantly increased in the NLRP3 and NLRP3 + morphine group. Conclusion Our study provides strong evidence that miR-223 could suppress the activities of NLRP3 inflammasomes ( NLRP3, apoptosis-associated speck-like protein, and Caspase-1) to relieve morphine analgesic tolerance in rats by down-regulating NLRP3.


Provider-patient roles in chronic disease management.
Health care provider-patient role relationships can influence patient satisfaction, adherence to treatment, and health outcomes positively. Existing models of role relationships reflect one of three approaches to clinical management--paternalism, consumerism, or shared decision making. These models may or may not reflect the reality of chronic disease management in clinical practice. To characterize the nature of chronic disease management from the perspectives of primary care providers, we asked four nurse practitioners and four internists to describe the roles they saw for themselves and for their patients. A qualitative approach using a descriptive mode supported the formulation of a narrative description of these roles. The roles reflected a paternalistic approach to chronic disease management. The shared decision making approach supported in the literature was not evident. This finding is important for health professional education and practice.


T15 idiotype expression in the murine response to phosphorylcholine is actively regulated by genes linked to the Igh-C locus.
In this report, we demonstrate the existence of a regulatory system that can determine the relative expression of individual clones (idiotypes) within the total immune response to PC. Studies of Igh-C-congenic mice and backcross analysis demonstrate that this regulation is controlled by genes linked to the immunoglobulin heavy chain locus. The regulation acts in a trans fashion. The regulatory genes of one parental allele can control the expression of idiotopes coded for by both parental alleles. This regulation does not appear to affect the quantity of the response, but could affect the quality of the response, depending on the potential repertoire and avidity of the individual clones available to respond to a given antigenic challenge.


Idiotypes of Lewis rat antibodies to encephalitogenic peptides of guinea pig myelin basic protein: in vitro and in vivo studies.
Lewis rat antibodies raised by immunization with encephalitogenic peptide 68-88 guinea pig myelin basic protein were purified by affinity chromatography and used to immunize rabbits. After exhaustive absorption of the rabbit antisera to remove anti-rat immunoglobulin activity, the antisera retained activity against the immunogen, shown by the ability to block reaction of radioiodinated peptide with the active site of the rat anti-peptide antibodies. Intrastrain idiotypic cross-reactivity was assessed by testing the rabbit antisera against a panel of Lewis anti-peptide antibodies. Each anti-idiotypic antiserum displayed a unique pattern of reactivity with the panel. Similar tests in which a panel of anti-peptide antibodies raised in F344 rats was used demonstrated the presence of interstrain cross-reactive idiotopes. When seven rabbit anti-idiotypic antisera were tested by pretreatment of rats before challenge with encephalitogen for effect in vivo, five were without effect. Of the remaining two, one caused a slight suppression of disease; the other enhanced disease compared to control animals.


Preventive role of carvedilol in adriamycin-induced cardiomyopathy.
Adriamycin though considered as an effective anticancer drug, leads to irreversible cardiomyopathy (CMP) and congestive heart failure (CHF). The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy (CMP) in cancer patients. Patients with lymphoreticular malignancy in whom ADR therapy was planned were randomized into two groups: carvedilol and control. Twenty seven patients each were enrolled in carvedilol and control groups. In the carvedilol group, 12.5 mg once daily oral carvedilol was given during six months. The patients were evaluated by echocardiography before and after chemotherapy. Left ventricular ejection fraction (EF) and systolic and diastolic diameters were calculated. At six months of follow up, six patients in the carvedilol group and five in the control group had died. The mean EF (63.19 vs. 63.88%) and fraction shortening (FS) (34 vs. 34.6) of the carvedilol group were similar at follow up, but in the control group, the mean EF (67.27 vs. 60.82%, P =0.003) and FS (38.48 vs. 34.6, P<0.05) at control echocardiography were significantly lower. In carvedilol group, both systolic and diastolic diameters were not changed, but in control group, systolic diameters were significantly increased compared with basal measures (left ventricular end systolic diameter = 28.26±5.50 mm vs. 31.25± 6.50 mm; P< 0.05). Prophylactic use of carvedilol in patients receiving anthracycline protected systolic functions of the left ventricle. Carvedilol can be a potential drug which can ameliorate ADR-induced CMP.


Chronic obstructive pulmonary disease.
A new report on chronic obstructive pulmonary disease by the British Lung Foundation criticises the lack of progress in tackling lung disease.


Positive and negative tissue-specific signaling by a nematode epidermal growth factor receptor.
The major determinants of receptor tissue tyrosine kinase (RTK) signaling specificity have been proposed to be Src homology 2 (SH2) binding sites, phosphotyrosine-containing oligopeptides in the cytoplasmic domain of the receptor. The Caenorhabditis elegans epidermal growth factor receptor homologue LET-23 has multiple functions during development and has eight potential SH2-binding sites in a region carboxyl terminal to its kinase domain. By analyzing transgenic nematodes for three distinct LET-23 functions, we show that six of eight potential sites function in vivo and that they are required for most, but not all, of LET-23 activity. A single site is necessary and sufficient to promote wild-type fertility. Three other sites activate the RAS pathway and are involved only in viability and vulval differentiation. A fifth site is promiscuous and can mediate all three LET-23 functions. An additional site mediates tissue-specific negative regulation. Putative SH2 binding sites are thus key effectors of both cell-specific and negative regulation in an intact organism. We suggest two distinct mechanisms for tissue-specific RTK-mediated signaling. A positive mechanism would promote RTK function through effectors present only in certain cell types. A negative mechanism would inhibit RTK function through tissue-specific negative regulators.


Relative sensitivity of leukemic (CML) and normal progenitor cells to treatment with the photosensitizer benzoporphyrin derivative and light.
Normal bone marrow and peripheral blood committed progenitor cells were found to be significantly more resistant to treatment with the photosensitizer benzoporphyrin derivative (BPD) and white fluorescent light (11 J/cm2) than were clonogenic cells from two cell lines (K562 and EM2) derived from nonremission patients with myelogenous leukemias. Bone marrow and peripheral blood committed progenitor cells from normal donors were also found to be more resistant to this treatment than were equivalent cells from patients with chronic myelogenous leukemia (CML). Normal bone marrow mononuclear cells grown in long-term marrow culture (LTMC) following treatment with BPD and light showed that no differences in stem cell productivity existed between control and treated samples. When bone marrow from CML patients was treated in the same manner, the numbers of progenitors detected in the nonadherent population during culture were greatly reduced compared to control material. Two rounds of PCR using nested primers to detect BCR-ABL mRNA showed that while this treatment significantly decreased the numbers of stem cells bearing the Philadelphia chromosome, it did not eliminate them.


Regulation of sodium transport by steroid hormones.
The main mechanisms involved in the regulation of sodium transport by steroid hormones are briefly reviewed. The respective roles of the apical epithelial sodium channel, which is likely to be the limitant step of steroid-regulated transepithelial sodium transport, and Na,K-ATPase are described. Regulation of these ion transporting proteins by aldosterone and glucocorticoid hormones, probably via a two step mechanism (rapid activation of channels or pumps by unknown regulators, and modulation of the transcription/translation rate of these transporters), is discussed. The mechanisms of mineralocorticoid selectivity, that is, the integrated process allowing a specific action of aldosterone, in spite of high concentrations of glucocorticoids that crossbind with aldosterone to the mineralocorticoid receptor (MR), are explained, as is the role of the enzyme 11 beta-hydroxysteroid dehydrogenase and the differential interactions of MR with steroid ligands and hormone responsive elements of DNA. Finally, synergism between aldosterone and antidiuretic hormone for the stimulation of sodium transport is evoked.


Friedrich Heinrich Lewy (1885-1950) and his work.
In 1912, Friedrich Heinrich Lewy first described the inclusion bodies named after him and seen in paralysis agitans (p.a.). Tretiakoff had found (1919) that the nucleus niger is most likely to be affected but in a subsequent large-scale series of post-mortem examinations (1923). Lewy was able to confirm this for a minority of cases only, with the exception of those that displayed postencephalitic Parkinsonism (and an unknown number of atypical Parkinson syndrome cases not identified until the 1960s). In a speculative paper (1932), he saw similarities between inclusion bodies in p.a. and viral diseases like lyssa and postulated a viral genesis of p.a. In a historical review of basal ganglia diseases (1942), he did not mention the putative significance of the inclusion bodies for the post-mortem diagnosis. It seems that their importance was seen only after Lewy's death, long after Tretiakoff's initial naming of the 'corps de Lewy'. Lewy, however, had already described their diffuse and cortical distribution (1923). An identification of diffuse Lewy body disease or dementia followed much later. Lewy's career in many diverse branches of neurology and internal medicine was strongly affected by World War I and the difficult situation faced by Jews in Germany. Shortly after the Neurological Institute was founded in Berlin in 1932 (as a clinic and research institute), he was forced, in 1933, to emigrate. His exile in England and the United States mirrors the fate of many German Jews and academics in the first half of the 20th century.


Mechanical behavior of ethylene vinyl acetate copolymer (EVA) used for fabrication of mouthguards and interocclusal splints.
In the present investigation, an experimental dental arch model fabricated in epoxy was assayed in Kratos universal testing machine to study the mechanical behavior of ethylene and vinyl acetate copolymer (EVA) in the form of mouthguard for sports and flat plate. The following variables were considered: thickness (3 and 4-mm plates), temperature (room and mouth temperature) and presence/absence of artificial saliva. Mechanical properties of EVA were tested under compressive strength: apparent absorbed energy (J.mm-1), maximum tension (N.mm-1), maximum dislocation (mm) and maximum strength (N). Data were recorded and modeled mathematically. Regarding the absorbed energy, maximum tension and maximum force, it was verified that the higher the thickness of the mouthguards, the better the results of force dissipation and redirection to the system and to several regions of the dental arch. In the presence of saliva and close to mouth temperature, the material responded positively to these alterations, resenting increased ductibility as well as improved mechanical responses. Regarding maximum dislocation, it was observed a better accommodation of the occlusion under conditions that simulate those observed in the oral environment. In conclusion, EVA proved to be an adequate material for fabrication of mouthguards and interocclusal splints. In addition, EVA showed good results in force dissipation and demonstrated a shock-absorbing capacity and a great protection potential.


Three-dimensional knee joint moments during performance of the bodyweight squat: effects of stance width and foot rotation.
The purpose of this investigation was to assess the effects of stance width and foot rotation angle on three-dimensional knee joint moments during bodyweight squat performance. Twenty-eight participants performed 8 repetitions in 4 conditions differing in stance or foot rotation positions. Knee joint moment waveforms were subjected to principal component analysis. Results indicated that increasing stance width resulted in a larger knee flexion moment magnitude, as well as larger and phase-shifted adduction moment waveforms. The knee's internal rotation moment magnitude was significantly reduced with external foot rotation only under the wide stance condition. Moreover, squat performance with a wide stance and externally rotated feet resulted in a flattening of the internal rotation moment waveform during the middle portion of the movement. However, it is speculated that the differences observed across conditions are not of clinical relevance for young, healthy participants.


Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes.
Oleuropein mediates most of the beneficial effects of olive products. This study examined the role of oxidative stress in the effects of oleuropein on lipid profile and blood glucose in rats with simultaneous renovascular hypertension and type 2 diabetes. Eight groups (n = 7-9 each) of male Sprague-Dawley rats including a control, a type 2 diabetic, a renovascular hypertensive, a sham, a simultaneously hypertensive diabetic receiving vehicle, and 3 simultaneously hypertensive-diabetic receiving 20, 40, or 60 mg/kg/day oleuropein were used. Four weeks after treatment, blood glucose, lipid profile, and biomarkers of oxidative stress were measured, and glucose tolerance test (GTT) was performed. Simultaneously hypertensive diabetic rats had significantly higher blood pressure, blood glucose, and serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and malondialdehyde. They also had lower serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and impaired glucose tolerance. Oleuropein significantly reduced blood pressure, blood glucose, and serum total cholesterol, LDL-C, triglyceride and malondoaldehyde. It also increased serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and improved glucose tolerance. The findings show that the model is associated with impaired glucose tolerance, and adverse lipid profile. They also show that oleuropein, partly by an antioxidant mechanism, improves glucose tolerance and changed lipid profile favorably.


Neuraminidase activity in human peripheral lymphocytes: its increase in chronic active liver disease.
The activity of neuraminidase (sialidase) in peripheral white blood cells was measured by a fluorometric method using 4-MU NANA as a substrate. The activity in mononuclear cells, which was predominantly lymphocytes, was 2.5 times higher than that in polymorphonuclear cells (neutrophils). The former's activity was directly proportional to the number of the cells, but that of the latter was found to be suppressed by an increasing number of cells. Thus, the increased number of PMN contaminated in MNC fraction somewhat obscured neuraminidase activity affecting suppressively . The enzyme activity in MNC of 25 control subjects (15 males and 10 females) was 254 +/- 73 pmoles per hour per 10(6) cells and there was no difference between the values in males and females (233 +/- 59 vs. 284 +/- 81). The activity in 20 patients with chronic active liver disease was significantly higher than that in controls (551 +/- 135, p less than 0.01). The amount of sialic acid in MNC, which was 1.4 times more than that in PMN, revealed a tendency for a positive correlation between neuraminidase activity. A new finding of the increase of lymphocyte neuraminidase activity was introduced and its pathological significance particularly in liver disease was discussed.


Soluble Epoxide Hydrolase Inhibition and Epoxyeicosatrienoic Acid Treatment Improve Vascularization of Engineered Skin Substitutes.
Autologous engineered skin substitutes comprised of keratinocytes, fibroblasts, and biopolymers can serve as an adjunctive treatment for excised burns. However, engineered skin lacks a vascular plexus at the time of grafting, leading to slower vascularization and reduced rates of engraftment compared with autograft. Hypothetically, vascularization of engineered skin grafts can be improved by treatment with proangiogenic agents at the time of grafting. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are inactivated by soluble epoxide hydrolase (sEH). EETs have multiple biological activities and have been shown to promote angiogenesis. Inhibitors of sEH (sEHIs) represent attractive therapeutic agents because they increase endogenous EET levels. We investigated sEHI administration, alone or combined with EET treatment, for improved vascularization of engineered skin after grafting to mice. Engineered skin substitutes, prepared using primary human fibroblasts and keratinocytes, were grafted to full-thickness surgical wounds in immunodeficient mice. Mice were treated with the sEHI 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), which was administered in drinking water throughout the study period, with or without topical EET treatment, and were compared with vehicle-treated controls. Vascularization was quantified by image analysis of CD31-positive areas in tissue sections. At 2 weeks after grafting, significantly increased vascularization was observed in the TPPU and TPPU + EET groups compared with controls, with no evidence of toxicity. The results suggest that sEH inhibition can increase vascularization of engineered skin grafts after transplantation, which may contribute to enhanced engraftment and improved treatment of full-thickness wounds.


A systematic review and meta-analysis of the effect of Vitamin D-fortified food on glycemic indices.
Some reports indicated that Vitamin D may improve glycaemia indices in diabetic patients. The aim of this systematic and meta-analysis was to evaluate effects of Vitamin D fortification on indices of glycemic control. Six databases (PubMed/Medline, ISI Web of Knowledge, Cochrane Library, Science Direct, Scopus, and Google Scholar) were searched, for randomized controlled trials that were published up to September 2018 and that compared the effect of Vitamin D-fortified food versus regular diet in relation to glycemic control. Of the 4,379 studies originally found, 11 articles remained to be assessed for meta-analysis. Vitamin D fortification was associated with a significant improvement in fasting serum glucose (mean difference [MD]: -2.772; 95% confidence interval [CI]: -5.435 to -0.109) and fasting serum insulin (MD: -2.937; 95% CI: -4.695 to -1.178) in patients with Type 2 diabetes mellitus. A diet with food enriched with Vitamin D was associated with a significant improvement in homeostatic model assessment of insulin resistance (MD: -1.608; 95% CI: -3.138 to -0.079) but was not associated with a significant reduction in hemoglobin A1C (MD: 0.034; 95% CI: -0.655 to 0.069). This meta-analysis indicates that Vitamin D fortification improves indices of glycemic control. Hence, food fortified with Vitamin D may be of potential therapeutic value in diabetic patients, as an adjuvant therapy.


Evaluation of pre-processing methods for tear fluid proteomics using proximity extension assays.
Tear fluid forms a potential source for biomarker identification, and can be minimal invasively collected via Schirmer strips. The lack of knowledge on the processing of Schirmer strips however complicates the analysis and between-study comparisons. We studied two different pre-processing methods, specifically the use of punches of the strip versus elution of the strip in a buffer. Tear fluid filled Schirmer strips were collected from 5 healthy participants, and divided into two halves over the length of the strip. In either part, punches or eluates were obtained from 4 different locations, from the first part touching the eye (head) to the end, to assess the protein distribution along the strips. The levels of 92 inflammatory proteins were measured in the punches/eluates using proximity extension assays. The punch method yielded higher protein detectability compared to the elution method (76% vs 66%; p ≤ 0.001). Protein expression level was found to be slightly higher in the head of the strip, however, 3 out of 5 punches from the head failed quality control. Protein expression levels over the remaining parts of the strips were similar. Our study showed beneficial use of punches of any part of the strip except the head in future biomarker research.


Physiological Replication of the Human Glomerulus Using a Triple Culture Microphysiological System.
The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health and disease. Previous models do not fully reflect all cell types and interactions present as they overlook mesangial cells within their 3D matrix. Herein, the development of a microphysiological system that contains all resident renal cell types in an anatomically relevant manner is presented. A detailed transcriptomic analysis of the contributing biology of each cell type, as well as functionally appropriate albumin retention in the system, is demonstrated. The important role of mesangial cells is shown in promoting the health and maturity of the other cell types. Additionally, a comparison of the incremental advances that each individual cell type brings to the phenotype of the others demonstrates that glomerular cells in simple 2D culture exhibit a state more reflective of the dysfunction observed in human disease than previously recognized. This in vitro model will expand the capability to investigate glomerular biology in a more translatable manner by the inclusion of the important mesangial cell compartment.


Unique luminal localization of VGAT-C terminus allows for selective labeling of active cortical GABAergic synapses.
Neurotransmitter uptake into synaptic vesicles is mediated by vesicular neurotransmitter transporters. Although these transporters belong to different families, they all are thought to share a common overall topology with an even number of transmembrane domains. Using epitope-specific antibodies and mass spectrometry we show that the vesicular GABA transporter (VGAT) possesses an uneven number of transmembrane domains, with the N terminus facing the cytoplasm and the C terminus residing in the synaptic vesicle lumen. Antibodies recognizing the C terminus of VGAT (anti-VGAT-C) selectively label GABAergic nerve terminals of live cultured hippocampal and striatal neurons as confirmed by immunocytochemistry and patch-clamp electrophysiology. Injection of fluorochromated anti-VGAT-C into the hippocampus of mice results in specific labeling of GABAergic synapses in vivo. Overall, our data open the possibility of studying novel GABA release sites, characterizing inhibitory vesicle trafficking, and establishing their contribution to inhibitory neurotransmission at identified GABAergic synapses.


Onychomycosis treated with a dilute povidone-iodine/dimethyl sulfoxide preparation.
Povidone-iodine (PVP-I) 10% aqueous solution is a well-known, nontoxic, commonly used topical antiseptic with no reported incidence of fungal resistance. We have been using a low-dose formulation of 1% PVP-I (w/w) in a solution containing dimethyl sulfoxide (DMSO) in our clinical practice for a variety of indications. Presented here is our clinical experience with this novel formulation in a severe case of onychomycosis that was resistant to any other treatment. A 49-year-old woman who had been suffering from severe onychomycosis for years presented after failing to find any remedy including over the counter (OTC), topical, and systemic oral prescribed therapies. The topical povidone-iodine/DMSO system was very effective in this case at alleviating the signs and symptoms of onychomycosis. This novel combination warrants further investigation in randomized, controlled trials to further elucidate its clinical utility.


An evaluation of the use of retrospectively acquired preoperative AOFAS clinical rating scores to assess surgical outcome after elective foot and ankle surgery.
The use of retrospectively acquired preoperative AOFAS rating scores in clinical research to assess the outcomes of elective foot and ankle surgery has not been validated. The data obtained utilizing this methodology may misrepresent the results and lead to spurious conclusions. This investigation compared preoperative AOFAS Ankle-Hindfoot scores obtained before and after surgery from patients who had undergone elective surgery to determine if retrospectively acquired scores match those collected prospectively. Only two out of 47 patients (4%) recalled identical AOFAS scores. The mean difference between the preoperative scores (preoperative score obtained after surgery minus preoperative score obtained before surgery) was -5.3 points. Fifteen patients (32%) had preoperative scores that differed by 20 points or more. Kappa statistics found little agreement among the five elements that comprised the two preoperative scores when responses obtained before and after surgery were compared to one another. The results suggest that preoperative clinical rating scores obtained after elective surgery are a poor predictor of the patient's preoperative condition and that studies which employ retrospectively acquired preoperative AOFAS clinical rating scores may overestimate the benefit of surgery.


Silanization of Sapphire Surfaces for Optical Sensing Applications.
Well-characterized silane layers are essential for optimized attachment of (bio)molecules enabling reliable chem/biosensor performance. Herein, binding properties and orientation of 3-mercaptopropyltrimethoxysilane layers at crystalline sapphire (0001) surfaces were determined by water contact angle measurements, infrared reflection absorption spectroscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. Infrared reflection absorption spectroscopy measurements suggest an almost perpendicular arrangement of the MPTMS molecules to the substrate surface. Adhesion force studies between a silicon nitride AFM tip and modified sapphire, gold, and silicon dioxide substrates were investigated by peak force tapping atomic force microscopy and used to define the silane binding properties on these surfaces. As expected, the Al-O-Si bond was determined to be responsible for the layer formation at the sapphire substrate surface.


Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson's disease restoring striatal synaptic plasticity.
Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of N-methyl-d-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas.


Variation in rates of sexual assault crisis counsellor usage during forensic examination in California: an observational study.
A critical asset to post-assault care of survivors is support from sexual assault crisis counsellors (SACCs). We sought to elucidate variation in implementation between California counties in SACC accompaniment during Sexual Assault Forensic Examination (SAFE). SACC attendance data from 2019 was obtained from the California Governor's Office of Emergency Services (CalOES). To assess SACC attendance rates during SAFEs, we requested SAFE quantity data from sheriffs and public health departments, the State Forensic Bureau, and the California Department of Justice (DOJ), but all requests were unanswered or denied. We also sought SAFE data from District Attorneys (DAs) in each county, and received responses from Marin and Contra Costa Counties. To estimate numbers of SAFEs per county, we gathered crime statistics from the Federal Bureau of Investigation's (FBI's) Uniform Crime Reporting Program and OpenJustice, a transparency initiative by the California DOJ. For each data source, we compared SACC attendance to SAFE quantities and incidences of sexual assault statewide. At the state level, data on SACC attendance per CalOES and DOJ archival data on sexual assault were used to approximate relative rates of SACC accompaniment at SAFEs; 83% (30 of 36) of counties had values <50%. The joint sexual assault crisis centre for Contra Costa and Marin Counties reported that 140 SACCs were dispatched in 2019, while DAs in Contra Costa and Marin reported completion of 87 SAFEs in 2019, for a calculated SACC accompaniment rate of 161%. Proxy data sourced from FBI and DOJ crime statistics displayed significant inconsistencies, and DOJ data was internally inconsistent. SACC accompaniment at SAFEs appears to be low in most California counties, however, limited data accessibility and data discrepancies and inaccuracies (e.g., rates over 100%) prevented reliable determination of SACC accompaniment rates during SAFEs. Substantial improvements in data accuracy and transparency are needed to ensure survivors' adequate access to resources.


Immunohistochemical study of jaw cysts: different existence of keratins in odontogenic and non-odontogenic epithelial linings.
Keratins and secretory component (SC) were immunohistochemically examined in fresh tissue samples from 45 odontogenic and 35 non-odontogenic cysts. Lining epithelia of almost all cases contained keratins which reacted with polyclonal antibodies (Dako, Bio-Science), and no difference could be found between the two groups of lesions. By staining with two monoclonal antibodies against keratins, i.e., RGE53 (Bio-Science) and RKSE60 (Bio-Science), it was revealed that the epithelia of non-odontogenic cysts, which were columnar epithelium in most cases, had fully and positively reacted with RGE53, while none of the cases was positive for RKSE60. In contrast, the squamous linings of odontogenic cysts except for two cases did not react with RGE53, and few cases possessed RKSE60-reactive keratin. SC was also contradictory. All non-odontogenic cysts exhibited SC. Regarding each pair of non-odontogenic and odontogenic cysts covered with RGE53 and SC-positive, and RKSE60-negative squamous epithelium, it seemed reasonable from the staining results to conclude that the squamous linings were metaplastic from the columnar epithelium. Based on the results, concomitant examinations of SC with keratins will be helpful in deciding the epithelial derivation of jaw cysts.


Mitochondrial protein import under kinase surveillance.
Despite the simplicity of the yeast Saccharomyces cerevisiae, its basic cellular machinery tremendously mirrors that of higher eukaryotic counterparts. Thus, this unicellular organism turned out to be an invaluable model system to study the countless mechanisms that govern life of the cell. Recently, it has also enabled the deciphering of signalling pathways that control flux of mitochondrial proteins to the organelle according to metabolic requirements. For decades mitochondria were considered autonomous organelles that are only partially incorporated into cellular signalling networks. Consequently, only little has been known about the role of reversible phosphorylation as a meaningful mechanism that orchestrates mitochondrial biology accordingly to cellular needs. Therefore, research in this direction has been vastly neglected. However, findings over the past few years have changed this view and new exciting fields in mitochondrial biology have emerged. Here, we summarize recent discoveries in the yeast model system that point towards a vital role of reversible phosphorylation in regulation of mitochondrial protein import.


Reactivation in calves of latent infection by Bovid herpesvirus-4.
Nine calves, six of which had been infected with strain 85/BH 16TV and three with strain 85/BH 232TN of Bovid herpesvirus-4 (BHV-4), were treated with dexamethasone (DMS) three months after infection. DMS administration did not induce any clinical signs of disease, but BHV-4 was isolated from the nasal swabbings of all calves for a maximum of 8 days after the start of DMS treatment. The virus was also isolated from the nerve tissues, nasal mucosa, lymph nodes, lung and spleen of 4 calves that were killed at different stages (3, 5, 7 days) of the DMS treatment. Intranuclear inclusions associated with cellular shrinkage were found in the neural tissues of calves killed either 3 or 5 days after the start of DMS treatment. Unexpectedly, a latent infection by infectious bovine rhinotracheitis (IBR) virus was reactivated. The virus was isolated from the nasal swabbings of two calves and also from the brain, cerebellum and nasal mucosa of one calf killed 5 days after the start of DMS treatment.


Studies on Evaluation of the Thermal Conductivity of Alumina Titania Hybrid Suspension Nanofluids for Enhanced Heat Transfer Applications.
Extensive investigations were made and empirical relations were proposed for the thermal conductivity of mono-nanofluids. The effect of concentration, diameter, and thermal properties of participating nanoparticles is missing in the majority of existing thermal conductivity models. An attempt is made to propose a model that considers the influence of such missing parameters on the thermal conductivity of hybrid nanofluids. Al2O3-TiO2 hybrid nanofluids have a 0.1% particle volume concentration prepared with distinct particle volume ratios (k - 1:6 - k, k = 1 to 6) in DI water. The samples were characterized, and the size and shape of the nanoparticles were verified. Also, the influence of varying particle volume ratios and the fluid temperature (varying from 283 to 308 K) were examined. 2.4 and 2.1% enhancements were observed in the thermal conductivity of alumina (5:0) and titania (0:5) nanofluids (having 0.1% volume concentration), respectively. Due to the low thermal conductivity of titania nanoparticles, the conductivity of the hybrid solution is above that of titania and below that of alumina nanofluids. An empirical relation for the thermal conductivity of hybrid nanofluids is established and validated considering the individual particle size, volume ratio, and thermal conductivity of particles.


Evaluation of the digestibility of nutrients in pigs by ileal cannulation technique.
A simple T-cannula was surgically inserted into the ileum of growing female Large White x Dutch Landrace swine. Chymus samples collected with the help of the cannula were analysed to determine the apparent digestibility of different dietary nutrients such as dry matter, crude protein and starch, as well as of some essential amino acids. The following three experiments were conducted: (I) of the cereals, the "Tewo" triticale variety fed alone and in 1:1 concentrate mixtures with wheat or maize was studied; (II) waxy maize hybrids and maize hybrids of normal endosperm were compared without treatment and after treatment by the Bocchi technology; (III) untreated and extruded maize supplemented either with extracted soybean or with extracted sunflower was also tested. The ileal digestibility of protein, amino acids and starch was determined and compared with values obtained by conventional (faecal) analysis. When feeding triticale alone or in combination with wheat or maize, the ileal digestibility of crude protein and amino acids increased as a result of feeding the cereal combinations (e.g. crude protein 72-79%, lysine 75-79%, threonine 63-78%, methionine 74-86%). Comparison of the two maize hybrids revealed that, with the exception of methionine, lysine and tyrosine, the amino acids of the waxy hybrid had higher ileal digestibility. Treatment of the normal hybrid by the Bocchi technology caused a significant improvement in the ileal digestibility of cystine, isoleucine, lysine, valine, and dry matter. This treatment also improved the faecal digestibility of all test nutrients but methionine. Bocchi treatment of the waxy hybrid significantly improved the ileal digestibility of isoleucine, leucine, methionine, tyrosine and valine, and the faecal digestibility of cystine, dry matter, and crude protein. No major variety- or treatment-related differences were found in the digestibility of starch. As a result of extrusion, the digestibility of nutrients of the soybean + maize mixture increased from 61.6% to 70.3% (crude protein), from 41.1% to 59.4% (threonine), from 60.1 to 72.0% (methionine), and from 70.7% to 82.7% (lysine). The same treatment of the sunflower + maize mixture increased the digestibility of crude protein from 80.6% to 84.5%, that of threonine from 78.1% to 80.6%, that of methionine from 79.7% to 84.3%, while that of lysine from 61.4% to 72.3%. The ileal digestibility of starch was 97-98% for both mixtures. As a result of extrusion, most of the faecal digestibility values showed a significant improvement for both the soybean- and the sunflower-containing mixtures. The favourable effect exerted by extrusion on the digestibility of nutrients is markedly influenced by the feed components.


Vitagnus an estrogen-riched herbal remedy used in sexual dysfunction: A randomized clinical trial.
Sexual dysfunction is a common problem in the postmenopausal period. Vitagnus is a phytoesterogen containing herb, which can bind to estrogen receptors and modulate their function. In this study, we evaluated the efficacy of oral vitagnus solution on sexual dysfunction improvement among postmenopausal women in North Khorasan Province, Iran. The present study was a double-blind clinical trial on 60 retired female teachers who visited the retirement center of North Khorasan Province from December 2019 until January 2021. Sampling was done in a convenience sampling. Allocation of intervention and placebo groups was done randomly by marking as A and B codes, respectively. Eligible married women aged 50-70 years had received 40 drops of vitagnus or placebo daily for 8 weeks. Female Sexual Function Index was filled on the first day, fourth, sixth, and eighth week after the intervention. Data were analyzed using SPSS V.23 and independent t-test, Mann-Whitney U, Chi-square, Fisher's exact test, and repeated measure ANOVA were used for analyzing descriptive and inferential data. P < 0.05 was considered as a statistically significant threshold. Data from Bonferroni post hoc test indicated that the mean total sexual function did not differ between the two groups before and at the end of the fourth week of intervention, but scores of total sexual function showed a significant difference at the end of the sixth (P = 0/003) and eighth week (P = 0/001) of intervention. Vitagnus drops, as a simple, cheap, and available herbal supplement, could affect the sexual function of women aged 50-70 and improve it.


A Neuroprotective Locus Modulates Ischemic Stroke Infarction Independent of Collateral Vessel Anatomy.
Although studies with inbred strains of mice have shown that infarct size is largely determined by the extent of collateral vessel connections between arteries in the brain that enable reperfusion of the ischemic territory, we have identified strain pairs that do not vary in this vascular phenotype, but which nonetheless exhibit large differences in infarct size. In this study we performed quantitative trait locus (QTL) mapping in mice from an intercross between two such strains, WSB/EiJ (WSB) and C57BL/6J (B6). This QTL mapping revealed only one neuroprotective locus on Chromosome 8 (Chr 8) that co-localizes with a neuroprotective locus we mapped previously from F2 progeny between C3H/HeJ (C3H) and B6. The allele-specific phenotypic effect on infarct volume at the genetic region identified by these two independent mappings was in the opposite direction of the parental strain phenotype; namely, the B6 allele conferred increased susceptibility to ischemic infarction. Through two reciprocal congenic mouse lines with either the C3H or B6 background at the Chr 8 locus, we verified the neuroprotective effects of this genetic region that modulates infarct volume without any effect on the collateral vasculature. Additionally, we surveyed non-synonymous coding SNPs and performed RNA-sequencing analysis to identify potential candidate genes within the genetic interval. Through these approaches, we suggest new genes for future mechanistic studies of infarction following ischemic stroke, which may represent novel gene/protein targets for therapeutic development.


Total syntheses of the archazolids: an emerging class of novel anticancer drugs.
V-ATPase has recently emerged as a promising novel anticancer target based on extensive in vitro and in vivo studies with the archazolids, complex polyketide macrolides which present the most potent V-ATPase inhibitors known to date, rendering these macrolides important lead structures for the development of novel anticancer agents. The limited natural supply of these metabolites from their myxobacterial source renders total synthesis of vital importance for the further preclinical development. This review describes in detail the various tactics and strategies employed so far in archazolid syntheses that culminated in three total syntheses and discusses the future synthetic challenges that have to be addressed.


Accurate DFT-D3 Calculations in a Small Basis Set.
Calculations of interaction energies of noncovalent interactions in small basis sets are affected by the basis set superposition error and dispersion-corrected DFT-D methods and are thus usually parametrized only for triple-ζ and larger basis sets. Nevertheless, some smaller basis sets could also perform well. Among many combinations tested, we obtained excellent results with the DZVP-DFT basis and newly parametrized D3 dispersion correction. The accuracy of interaction energies and geometries is close to significantly more expensive calculations.


Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography.
With the aim of developing more efficient gastric cancer screening programs for use in Japan, we studied a new screening program that combines serum pepsinogen (PG) testing and barium digital radiography (DR). A total of 17 647 middle-aged male subjects underwent workplace screening over a 7-year period using a combination of PG testing and DR. This program's effectiveness, as well as other characteristics of the program, was analyzed. Forty-nine cases of gastric cancer were detected (comprising 88% early cancer cases). The detection rate was 0.28%, and the positive predictive value was 0.85%. The PG test detected 63.3% of cases, DR detected 69.4% of cases, and both tests were positive in 32.7% of cancer cases. The two methods were almost equally effective, and were considerably more effective than conventional screening using photofluorography. Each screening method detected a distinct gastric cancer subgroup; the PG test efficiently detected asymptomatic small early cancer with intestinal type histology, while DR was efficient at detecting cancers with depressed or ulcerated morphology and diffuse type histology. The cost for the detection of a single cancer was much less than that for conventional screening. In fact, it is possible to further reduce the cost of detecting a single cancer to a cost comparable to that of surgically resecting a single gastric cancer. Thus, it is probable that a highly efficient gastric cancer screening system can be implemented by combining the two screening methods. Such a screening program would be beneficial in a population at high risk for gastric cancer.


2D MoS2 Neuromorphic Devices for Brain-Like Computational Systems.
Hardware implementation of artificial synapses/neurons with 2D solid-state devices is of great significance for nanoscale brain-like computational systems. Here, 2D MoS2 synaptic/neuronal transistors are fabricated by using poly(vinyl alcohol) as the laterally coupled, proton-conducting electrolytes. Fundamental synaptic functions, such as an excitatory postsynaptic current, paired-pulse facilitation, and a dynamic filter for information transmission of biological synapse, are successfully emulated. Most importantly, with multiple input gates and one modulatory gate, spiking-dependent logic operation/modulation, multiplicative neural coding, and neuronal gain modulation are also experimentally demonstrated. The results indicate that the intriguing 2D MoS2 transistors are also very promising for the next-generation of nanoscale neuromorphic device applications.


Correlates of Durable Viral Suppression (DVS) Among Criminal Justice-involved (CJI) Black Men Living with HIV in Louisiana.
Durable viral suppression (DVS) is needed to reduce HIV transmission risk and prevent new HIV infections. We examined changes in viral suppression and correlates of DVS among 97 criminal justice-involved (CJI) Black men living with HIV in Louisiana enrolled in a linkage, re-engagement, and retention in care intervention. Most participants (75%) were Black men who have sex with men. Forty-four percent (44%) were virally suppressed at baseline and only 20% had achieved DVS over a 12-month period. Multinomial logistic regression analyses showed that compared with DVS participants, those with no viral suppression (NVS) and some viral suppression (SVS) were more likely to have lived with HIV for a longer period of time and were less likely to be adherent at baseline. Medication adherence was critical for DVS among this sample of CJI Black men living with HIV who represent a high priority population for HIV care and treatment interventions.


New Insight into the Function of Dopamine (DA) during Cd Stress in Duckweed (Lemna turionifera 5511).
Dopamine (DA), a kind of neurotransmitter in animals, has been proven to cause a positive influence on plants during abiotic stress. In the present study, the function of DA on plants under cadmium (Cd) stress was revealed. The yellowing of duckweed leaves under Cd stress could be alleviated by an exogenous DA (10/20/50/100/200 μM) supplement, and 50 μM was the optimal concentration to resist Cd stress by reducing root breakage, restoring photosynthesis and chlorophyll content. In addition, 24 h DA treatment increased Cd content by 1.3 times in duckweed under Cd stress through promoting the influx of Cd2+. Furthermore, the gene expression changes study showed that photosynthesis-related genes were up-regulated by DA addition under Cd stress. Additionally, the mechanisms of DA-induced Cd detoxification and accumulation were also investigated; some critical genes, such as vacuolar iron transporter 1 (VIT1), multidrug resistance-associated protein (MRP) and Rubisco, were significantly up-regulated with DA addition under Cd stress. An increase in intracellular Ca2+ content and a decrease in Ca2+ efflux induced by DA under Cd stress were observed, as well as synchrony with changes in the expression of cyclic nucleotide-gated ion channel 2 (CNGC2), predicting that, in plants, CNGC2 may be an upstream target for DA action and trigger the change of intracellular Ca2+ signal. Our results demonstrate that DA supplementation can improve Cd resistance by enhancing duckweed photosynthesis, changing intracellular Ca2+ signaling, and enhancing Cd detoxification and accumulation. Interestingly, we found that exposure to Cd reduced endogenous DA content, which is the result of a blocked shikimate acid pathway and decreased expression of the tyrosine aminotransferase (TAT) gene. The function of DA in Cd stress offers a new insight into the application and study of DA to Cd phytoremediation in aquatic systems.


Regression of lung cancer by hypoxia-sensitizing ruthenium polypyridyl complexes.
The ruthenium (II) polypyridyl complexes (RPC), Δ-[(phen)2Ru(tatpp)]Cl2 (Δ-[3]Cl2) and ΔΔ-[(phen)2Ru(tatpp)Ru(phen)2]Cl4 (ΔΔ-[4]Cl4, are a new generation of metal-based antitumor agents. These RPCs bind DNA via intercalation of the tatpp ligand, which itself is redox-active and is easily reduced at biologically relevant potentials. We have previously shown that RPC 4(4+) cleaves DNA when reduced by glutathione to a radical species and that this DNA cleavage is potentiated under hypoxic conditions in vitro. Here, we show that 3(2+) also exhibits free radical-mediated DNA cleavage in vitro and that 3(2+) and 4(4+) both exhibit selective cytotoxicity toward cultured malignant cell lines and marked inhibition of tumor growth in vivo. The murine acute toxicity of RPCs 3(2+) and 4(4+) (maximum tolerable doses ~ 65 μmol/kg) is comparable with that for cisplatin (LD50 ~ 57 μmol/kg), but unlike cisplatin, RPCs are generally cleared from the body unchanged via renal excretion without appreciable metabolism or nephrotoxic side effects. RPCs 3(2+) and 4(4+) are shown to suppress growth of human non-small cell lung carcinoma (~83%), show potentiated cytotoxicity in vitro under hypoxic conditions, and induce apoptosis through both intrinsic and extrinsic pathways. The novel hypoxia-enhanced DNA cleavage activity and biologic activity suggest a promising new anticancer pharmacophore based on metal complexes with aromatic ligands that are easily reduced at biologically accessible potentials.


Implications of high-risk family studies for prevention of depression.
The high-risk family study is a powerful design that facilitates identification of early forms of expression of depression and premorbid vulnerability, risk, and protective factors that are important for defining prevention targets and program foci. This paper (1) highlights the strengths of high-risk studies for informing early intervention efforts; (2) summarizes findings of familial aggregation from controlled high-risk studies of depression; and (3) briefly reviews evidence for potential mediators (i.e., early forms of expression, vulnerability factors) that explain familial risk and for moderators (i.e., interactive risk and protective factors) that enhance or minimize familial risk. New data from the Yale High-Risk Study of Comorbidity of Substance Use and Affective Disorders are presented to exemplify strategies for identifying specific familial pathways to depression among offspring of parents with substance and anxiety disorders. Likewise, parental depression is associated with a range of emotional and behavioral problems, including anxiety and conduct disorder, in their offspring. These nonspecific effects, together with emerging findings on mechanisms of risk, support early intervention efforts that target a range of youth at risk for depression through multipronged approaches that attend to the individual characteristics of the child and parent, clinical comorbidity, and the broader family and social context.


[Immunoenzyme and immunohistochemical analysis of class III alcohol dehydrogenase from human testis].
An enzyme-linked immunosorbent assay on the basis antialcohol dehydrogenase III (ADH III) monospecific antiserum has been devised. The immunoreactive protein content determined in two samples of human testis autopsy material was 1,288 and 1,047 mg/g of wet weight. ADH III has been revealed in all types of human testicular cells with the maximal content in spermatocytes and spermatogonia.


The importance of the Lewis base in lithium mediated metallation and bond cleavage reaction of allyl amines and allyl phosphines.
Metallation of two analogous N- and P-allyl molecules Ph2NCH2CHCH2 and Ph2PCH2CHCH2 with nBuLi have shown contrasting reactivities based on the choice of Lewis donor. With metallation of the alpha carbon atom was achieved regardless of the Lewis donor used while in comparison metallation of showed an unexpected donor denticity dependence with P-C bond clevage induced with the tri-dentate PMDETA. Complementary DFT and solution studies rationalise this outcome.


The Voice of God.
Prayer and verbally answered prayer would seem to offer powerful evidence in relation to the question of human agency. Forty members of an English Pentecostal group completed a questionnaire on prayer: 25 reported an answering voice from God, 15 of them hearing Him aloud. The latter groups were interviewed and characteristics of phenomenology and context elicited. The voice of God cannot be held to be ipso facto pathological and many reported its utility in situations of doubt or difficulty.


Mitochondrial motility in axons: membranous organelles may interact with the force generating system through multiple surface binding sites.
In living tissue, membrane-bound organelles, including mitochondria, move along parallel cytoplasmic pathways. Motion is directed and tends to be confined to a single path. Deviations from this single path motion are rare. When present, however, they tend to occur at points of intersection of cytoskeletal linear elements (LE). Such intersections are relatively uncommon in intact axons and extruded axoplasm. However, we have found that such intersections can be produced in extruded preparations by shear forces directed tangential to the axoplasmic surface. We have studied the detailed behavior of mitochondria in extruded squid axoplasm. Special attention was directed to the relationship between mitochondrial shape changes and orientation of cytoskeletal LE. The most striking of these changes in shape is branching. In this process, the mitochondrion transiently assumes a triradial (three-ended) shape. This appearance may be maintained for seconds to minutes before the normal cylindrical shape is resumed by absorption of either the newly formed end or, more commonly, one of the original ends. The frequency of branching appears to be dependent on the degree of cytoskeletal organization. It becomes more common as the number of apparent intersections between cytoskeletal LE increases. Further, the formation of new ends seems to occur along paths defined by cytoskeletal elements. These observations suggest that the mitochondrial membrane is multivalent. That is, it contains multiple sites capable of interacting with the axonal force generation apparatus. Furthermore, LE in the cytoskeleton may indicate the paths along which these interactions are permissible.


17 beta-estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP.
The process by which 17 beta-estradiol rapidly modulates the excitability of neurons in the ventromedial hypothalamus, a facilitation center of female sexual behavior and satiety center of feeding behavior, through mediation by cyclic nucleotides, was investigated by intracellular recording from the guinea pig brain slice preparations. Two types of short-term responses were produced by depolarization with decreased K+ conductance and hyperpolarization with increased K+ conductance. These two responses were enhanced by the phosphodiesterase inhibitor, isobutylmethylxanthine. However, the specific adenylate cyclase activator, forskolin, enhanced only the depolarization. The analogue of cyclic adenosine 3',5'-monophosphate (cAMP), 8-bromo-cAMP, induced only depolarization, the ionic mechanism of which was similar to that of 17 beta-estradiol. In addition, the possibility of non-specific effects of cyclic nucleotides was precluded by an experiment using an analogue of cyclic guanosine 3',5'-monophosphate (cGMP), 8-bromo-cGMP, which hyperpolarized neurons. Thus, the present study strongly suggests that the production of depolarizing responses of neurons in the hypothalamus produced by estradiol is specifically mediated through cAMP.


A Joint Space-Time Array for Communication Signals-Based on a Moving Platform and Performance Analysis.
A joint space-time array for communication signals is constructed in this paper to settle the contradiction between the performance of angle estimation and the array aperture. It introduces Doppler information caused by platform motion into the signal processing to obtain favorable performance with limited array aperture. We analyze the theoretical performance in the aspects of distinguishable source number, spatial resolution and Cramér-Rao bound (CRB), respectively. Both theoretical analysis and simulation results demonstrate that the proposed space-time array can give rise to a significant enhancement in achievable array performance.


Tetrahydroisoquinoline derivatives of enkephalins: synthesis and properties.
Tetrahydroisoquinolines (TIQs) are endogenous alkaloid compounds deriving from the non-enzymatic Pictet-Spengler condensation of catecholamines with aldehydes. These compounds are able to unsettle catecholamines uptake and release from synaptosomes and have been detected in urine and in post-mortem Parkinsonian brains. We have obtained in vitro, by the reaction of dopa-enkephalin (dopa-Gly-Gly-Phe-Leu) with acetaldehyde in the presence of rameic ions, a TIQ derivative of Leu-enkephalin. The isolation and the recovery of the peptide was obtained by HPLC. The acid hydrolysis and the subsequent analysis of the peptide lysate by the Amino acid analyser clearly revealed the absence of dopa, while the electrospray ionisation mass spectrometry showed that the sequence of the enkephalin derivative was the following: 3-carboxy-salsolinol-Gly-Gly-Phe-Leu (TIQ-enkephalin). This compound was not a good substrate for microsomal aminopeptidase and pronase with respect to Leu-enkephalin. Tested in the binding assay, the TIQ-enkephalin exhibited a very poor affinity toward the enkephalin receptors. When the TIQ-enkephalin was incubated with tyrosinase or peroxidase/H(2)O(2), the formation of TIQ-opio-melanins occurred.


Staggered alignment of quadrupolar molecules inside carbon nanotubes.
Grand canonical Monte Carlo molecular simulations of the adsorption of three quadrupolar moleculesnitrogen (N(2)), carbon dioxide (CO(2)), and perfluoroethane (C(2)F(6))within single walled carbon nanotubes are reported. A unique slanted ordering is seen in the nanotubular systems (1-D geometry) which has not been reported before nor is present in slit nanopores (2-D geometry), and is due to the particular combination of steric effects and the unique anisotropic attraction experienced by these fluids.


Lead and copper-induced hormetic effect and toxicity mechanisms in lettuce (Lactuca sativa L.) grown in a contaminated soil.
Lead (Pb) and copper (Cu) contamination seriously threatens agricultural production and food safety. This study aims to investigate Pb and Cu induced hormetic effect and toxicity mechanisms in lettuce (Lactuca sativa L.) and establish reliable empirical models of potentially toxic elements (PTEs) transfer in the soil-plant system. The content and distribution of Pb and Cu at subcellular levels in lettuce plants were examined using inductively coupled plasma-mass spectrometry, differential centrifugation and micro-X-ray fluorescence spectroscopy. The PTE-loaded capacity of Pb that ensures food safety was lower than that of Cu in the studied soil, but the PTE-loaded capacity of Pb that limits yield was higher than that of Cu. Lead in lettuce roots mainly accumulated in the cell wall (41%), while Cu mainly accumulated in the vacuoles (46%). The Pb and Cu were primarily distributed in the radicle of lettuce seeds under severe PTE stress, resulting in no seed development. Iron plaque formed on the root surface of lettuce seedlings and sequestered Pb and Cu via chelation. At the same concentration, lettuce was less tolerant to Cu in contaminated soil than Pb due to the higher activity of Cu ions in the soil. Lead was more phytotoxic to lettuce than Cu, however, since the radicle emerged from the seed under severe Cu levels, while it did not protrude under severe Pb levels. The potentially damaging effect of Pb in the visually healthy lettuce appeared to be higher than that of Cu under the same soil contamination level.


Linking the parts: an exemplar of philosophical and practical issues in holistic nursing.
This paper offers an analysis of some of the challenges of holism, particularly the challenges relating to co-operation and role indeterminacy. It uses the work of one group of nurses (specialist paediatric oncology nurses) to exemplify these issues, and it draws upon some empirical research into their work. These nurses work to provide a link between hospital and home for families with children with cancer, but it is suggested that the fundamental issues they face, (a) in linking the parts of the system, and (b) in linking the parts of care as it is experienced, are shared by anyone who subscribes to the holistic nursing. Issue (a) raises questions of professional boundary crossing, and calls upon diplomatic and micro-political skills. Issue (b) raises questions about the boundaries of health care, and calls upon skills of 'translation' and emotional labour. The value of holism is not questioned but the paper illustrates how aiming for holistic care inevitably opens up philosophical and practical problems and concerns.


An unusually prolonged duration of spinal anaesthesia following 0.5% levobupivacaine.
Spinal anaesthesia is the method of choice for elective caesarean delivery. Levobupivacaine may produce a sensory and motor block that is different from that produced by bupivacaine, the most popular local anaesthetic for parturients undergoing caesarean section (CS). We present a case of unexpectedly prolonged spinal anaesthesia following a successful spinal block with levobupivacaine. There was no evidence of any neurological injury in this patient during injection.


Significantly dysregulated genes in osteoarthritic labrum cells identified through gene expression profiling.
The aim of the present study was to explore the molecular basis and identify significant genetic alterations in acetabular labrum cells associated with osteoarthritis (OA). Gene expression data of osteoarthritic and normal human labrum cells were downloaded from a public database and reanalyzed. Significant differentially expressed genes (DEGs) were acquired by performing a thorough analysis of microarray data between the OA acetabular labrum cells and control cells. Key genes in OA labrum cells were revealed by a combination of weighted gene co‑expression network analysis (WGCNA) and protein‑protein interaction (PPI) analysis. Literature mining and drug screening were further performed for these key genes. In total, 141 DEGs between OA and normal labrum cells were identified. In addition, WGCNA and PPI analysis identified 23 DEGs as key genes in the OA labrum. All the key genes were significantly downregulated in OA labrum cells and were grouped into two different WGCNA‑PPI common subnetworks. Kinase insert domain receptor (KDR), CD34, cadherin 5 (CDH5), Fms related tyrosine kinase 1 (FLT1) and asporin were hub nodes in the PPI network of DEGs. These key genes were significantly enriched in functional clusters of transforming growth factor, alkaline phosphatase, bone morphogenic protein and extracellular matrix. Drug screening analysis identified several drugs targeting the key genes, including arachidonic acid, yohimbic acid and mimosine. The results of the present study indicate that the changes of FLT1, KDR, CD34 and CDH5 in acetabular labrum cells may be involved in the pathogenesis of OA and could serve as biomarkers and therapeutic targets of OA. Additionally, arachidonic acid, yohimbic acid and mimosine may act as potential drugs for OA.


Impact of coated TiO2-nanoparticles used in sunscreens on two representative strains of the human microbiota: Effect of the particle surface nature and aging.
The impact of two differently coated TiO2-nanoparticles (NPs) was evaluated on two representative bacteria from the cutaneous microbiota (Staphylococcus aureus and Pseudomonas fluorescens) in conditions of use. Particles were coated in order to exhibit either hydrophilic or hydrophobic behavior. A first exposure scenario within some fresh/aged model emulsions was developed in order to measure both the impact of the NPs presence and their surface nature during the emulsions conservation. Thanks to this protocol, it was demonstrated that, during aging, the hydrophobic NPs modified the physicochemical characteristics of the emulsions, such as the pH or the colloids sizes, and favored the development of potential pathogenic bacteria. A second scenario was then envisaged, aiming to mimic the exposition of the skin, especially of the cutaneous bacteria, to NPs. Tested NPs were extracted from emulsions with different aging, and results highlighted the importance of both the NP coating nature and their history in emulsion. The different NPs impacts on the bacteria growth were discussed and linked to their surface properties modifications during aging, as polarity and charges. Finally, through two exposition scenarios, this work highlights the major impact of the NPs surface properties on bacteria.


Alpha ganglion cells of the rabbit retina lose antagonistic surround responses under dark adaptation.
Alpha ganglion cells from the midperiphery of the rabbit retina were recorded intracellularly under visual control, in a superfused everted eyecup, and labeled with HRP. Their physiology and large somata with broad dendritic arbors identified them as uniform populations of ON- and OFF-center alpha ganglion cells, which typically displayed transient/sustained light-evoked responses. When dark adapted, the light-evoked responses from both ON- and OFF-center alpha ganglion cells were more sustained than those generally seen under light-adapted conditions. During dark-adapted (scotopic) conditions, stimulation with dim full-field illumination and small spots, either positioned over the soma or displaced 450 microns from the soma, all elicited pure center responses. After light adaptation (photopic conditions), the displaced small spots that previously evoked center responses elicited antagonistic surround responses from both ON- and OFF-center cells. Thus, as originally described in cat retina (Barlow et al., 1957), the receptive-field organization of ganglion cells changed between dark and light adaptation, and an absence or presence of surround antagonism was indicative of scotopic versus photopic states.


Acceptance of ostomy and the visitor role in a self-help group for ostomy patients.
The helper therapy principle, which underscores the benefits from helping another person, has been relatively unexplored in the self-help movement. This study examined whether persons enrolled in the United Ostomy Association, a self-help group for ostomates, who functioned in a helping role as visitors demonstrated a greater level of acceptance of their ostomy than those persons enrolled in the same group who have not served in the visitor role. Results indicated that visitors' acceptance of their own ostomies was significantly higher than nonvisitors'. The length of time since visitors and nonvisitors had their first ostomy surgery was not a significant factor in the person's acceptance of ostomy. There was a significant relationship between the person's level of acceptance of ostomy and the length of time the individual had served in the visitor role. Serving in the visitor role contributed significantly to predicting a higher level of acceptance of the ostomy. The length of time since surgery was a significant predictor to serving in the visitor role. Factors of age, sex, type of ostomy, and length of time since surgery did not contribute significantly to predicting a higher level of acceptance of the ostomy.


Participation of Increased Circulating MAIT Cells in Lung Cancer: a Pilot Study.
Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that regulate the immune response via rapidly releasing inflammatory factors, including during progression of some tumors. However, the immunological role of MAIT cells is still unclear in lung cancer. We measured percentage, partial function, and clinical correlation of circulating MAIT cells from lung cancer patients through flow cytometry. Lung cancer patients displayed a high concentration of CD4+, CD8+, and activated CD38+CD8+MAIT cells, and a decrease of PD1+ double negative (DN) MAIT cells in peripheral blood. Meanwhile, increased levels of interferon-γ, interleukin (IL)-6, and 8 were examined in the serum of lung cancer patients. Importantly, we discovered a statistically positive association between accumulation of CD38+CD8+MAIT cells and reduced progression-free survival of lung cancer patients. While preliminary, the altering frequency of MAIT cells might be involved in dysfunctional immune response in lung cancer.


Serum levels of parathyroid hormone and parathyroid-related peptide in psoriasis.
Psoriasis is a common skin disorder that may be triggered by hormonal disturbances, among other factors. Some studies have demonstrated an elevation of serum parathyroid hormone (PTH) levels in psoriasis and several other diseases of keratinization of unknown aetiology. PTH-related peptide (PTH-rp), on the other hand, is a potent inhibitor of epidermal cell growth factor and is not expressed in psoriatic skin. Serum levels of this peptide have not been reported in psoriasis. Immunoassay was used to measure serum PTH and PTH-rp in 22 patients with plaque-type psoriasis before and after treatment with mometasone furoate. Results were compared with a group of 20 healthy, non-psoriatic volunteers. Serum PTH levels were significantly elevated in the psoriatic group compared with the control group (p=0.001) and were significantly reduced after treatment (p=0.01). A correlation was found between pretreatment serum PTH levels and psoriasis area and severity scores (PASI) (r=0.42; p=0.01). In contrast, serum PTH-rp levels were not different between psoriatics and controls and were not affected by treatment. These findings indicate that serum PTH concentrations reflect disease activity in patients with psoriasis.


Atorvastatin and simvastatin, but not pravastatin, up-regulate LPS-induced MMP-9 expression in macrophages by regulating phosphorylation of ERK and CREB.
Statins suppress expression of pro-inflammatory cytokines in endothelial cells, whereas they enhance it in immune cells. Pro-inflammatory cytokines and lipopolysaccharide (LPS) induce matrix metalloproteinase (MMP)-9 gene expression in macrophages, which has been linked to progress of various inflammatory diseases. The aim of this study was to identify effects of various statins on LPS-induced MMP-9 gene expression in macrophages and microglia. MMP-9 expression was analyzed by real-time PCR or zymography. Effect of statins on activation of signaling pathways was analyzed by time-dependent phosphorylation of signaling molecules. Atorvastatin and simvastatin, but not pravastatin, up-regulated LPS-induced MMP-9 expression in murine RAW 264.7 macrophages and BV2 microglia. The phosphorylation duration of extracellular signal regulated kinases was extended by simvastatin, but not by atorvastatin or pravastatin. The up-regulation of LPS-induced MMP-9 gene expression by the statins was dependent on extracellular calcium ions and mediated by enhancing phosphorylation of cAMP-responsive element binding protein. Geranylgeranyl pyrophosphate, a precursor for cholesterol synthesis, could suppress up-regulation of LPS-mediated MMP-9 gene expression by atorvastatin and simvastatin. Atorvastatin and simvastatin-mediated up-regulation of LPS-induced MMP-9 gene expression in macrophages and microglia in vitro raises an important concern about use of the widely-prescribed statins in certain inflammatory conditions that are mediated by LPS.


Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems.
Considering the specific pH gradients of tumour microenvironments, a dual acid-responsive drug delivery system, which can respond to the tumor extracellular and intercellular pH stimuli, has been fabricated via simple host-guest recognition. Firstly, we synthesise 2,4,6-trimethoxybenzaldehyde modified dextran (Dex-TMBA) and mPEG-imine-β-cyclodextrin (PIC), respectively. And then, through the host-guest recognition between the cyclodextrin (CD) of PIC and the benzene ring of Dex-TMBA, a kind of dual acid-responsive supramolecular drug delivery system can be fabricated. Under neutral pH conditions, anticancer drugs can be loaded by forming supramolecular nanoparticles via the host-guest recognition. While, at tumor extracellular pH (∼6.8), the acid-labile benzoic-imine of PIC cleaves and the nanoparticles are amino positively charged to facilitate cell internalization. Subsequently, due to the hydrolysis of acetal bonds in Dex-TMBA under significantly increased acidity in subcellular compartments such as the endosomes (∼5.3), the loaded doxorubicin releases from the endocytosed drug delivery. This dual acid-responsive nanoparticles can efficiently load and release drugs, acting as drug delivery systems for enhancing anticancer efficiency.


Preventing transfusion-transmitted infections: issues related to migrating populations and increasing world travel.
Blood donations by emigrants or other travelers from distant lands require special attention for the prevention of transfusion-transmitted infections. The human immunodeficiency virus, type 1 (HIV-1) is only one of several bloodborne viruses that may be introduced into non-epidemic areas by transfusion and spread further by sexual intercourse, needles shared by drug users or mother-child transmission. Although transfusion-transmitted parasites, such as Trypanosoma cruzi, do not spread further in non-endemic areas in the absence of specific vectors, such unlikely infections may cause serious disease before a diagnosis is made. The challenges posed by transfusion-transmitted infections in a shrinking world require specific preventive strategies and enhanced clinical awareness for timely diagnosis and treatment.


A peculiar appendix: A case report.
Acute appendicitis is a clinical diagnosis with marked variations in the clinical presentation, the latter resultant of varied anatomical positions of the appendix. Here we present the first documented case of the vermiform appendix located in the ascending colon of a young South Asian male who presented with right upper abdominal pain. The ultrasound scan of the abdomen failed to visualise the appendix in the right iliac fossa. Persistent symptoms despite conservative therapy and elevated inflammatory markers warranted an open laparotomy. The histology further confirmed acute appendicitis. Atypical locations and congenital anomalies of the appendix are relatively rare entities. Appendicular duplication and hypoplasia are the predominant varieties of congenital anomalies. Caecal diverticula might mimic acute appendicitis despite the relative rarity and absence of all three layers of intestinal wall, which could be of use in distinguishing an abnormally located appendix. Such deviations from the norm lead to atypical clinical and imaging findings where operative interventions might be required in place of non-operative care, especially in instances of persistent symptomatology.


A wirelessly-powered homecage with animal behavior analysis and closed-loop power control.
This paper presents a new EnerCage-homecage system, EnerCage-HC2, for longitudinal electrophysiology data acquisition experiments on small freely moving animal subjects, such as rodents. EnerCage-HC2 is equipped with multi-coil wireless power transmission (WPT), closed-loop power control, bidirectional data communication via Bluetooth Low Energy (BLE), and Microsoft Kinect® based animal behavior tracking and analysis. The EnerCage-HC2 achieves a homogeneous power transfer efficiency (PTE) of 14% on average, with ~42 mW power delivered to the load (PDL) at a nominal height of 7 cm by the closed-loop power control mechanism. The Microsoft Kinect® behavioral analysis algorithm can not only track the animal position in real-time but also classify 5 different types of rodent behaviors: standstill, walking, grooming, rearing, and rotating. A proof-of-concept in vivo experiment was conducted on two awake freely behaving rats while successfully operating a one-channel stimulator and generating an ethogram.


Advances in Aesthetic Therapies: Plasma-Rich Protein Procedure for the Treatment of Alopecia.
Predominance of aesthetic options is growing and evolving to include procedures that have traditionally been much more invasive and fiscally challenging for the average patient. It is not uncommon now for the Canadian consumers to begin to look for lesser invasive options that show results significant enough to improve their appearance but that may not fall under the traditional health care coverage. One area that is evolving quickly is the nonsurgical treatment of hair loss. This is not a new condition, but generally the methods of treatment are not under the current health coverage; therefore, consumers are paying out of pocket to reduce or replace their hair loss. Recently, more options have evolved, and utilizing platelet-rich plasma has become more prevalent as a method to support hair growth and prevent hair loss.


Clinical outcome using the fluency stent graft for transjugular intrahepatic portosystemic shunt in patients with portal hypertension.
The objective of this study was to evaluate the clinical outcomes using the Fluency stent graft for transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension. From January 2008 to December 2011, 150 patients (110 male and 40 female with a mean age of 51 years) with portal hypertension underwent TIPS creation with the Fluency stent graft. Indications for TIPS treatment were variceal bleeding in 134 cases and refractory ascites in 16 cases. The clinical results pre- and postprocedure were evaluated. All 150 patients underwent a successful TIPS procedure without any technical complications. The portal pressure decreased from 24.3 ± 3.2 mmHg preoperatively to 15.1 ± 2.7 mmHg postoperatively (P < 0.001), and the portal flow velocity increased from 18.3 ± 4.6 cm/s to 55.6 ± 15.8 cm/s (P < 0.001). Emergency TIPS was performed in 18 patients with uncontrolled variceal bleeding. During hospitalization, the rates of shunt occlusion, hepatic encephalopathy, variceal rebleeding, and death were 1.3, 0.0, 1.3, and 2.0 per cent, respectively. At a mean follow-up of 24.1 ± 8.8 months, the rates of shunt occlusion, hepatic encephalopathy, variceal rebleeding, and death were 10.0, 15.3, 11.3, and 10.0 per cent, respectively. The main causes of death were hepatic failure, hepatic carcinoma, and recurrent variceal bleeding. The Fluency stent graft is effective in TIPS creation with high patency rates and improves the results of TIPS for portal hypertension.


A Novel Drosophila Model to Investigate Adipose Tissue Macrophage Infiltration (ATM) and Obesity highlights the Therapeutic Potential of Attenuating Eiger/TNFα Signaling to Ameliorate Insulin Resistance and ATM.
Obesity is a global health concern associated with various metabolic disorders including insulin resistance and adipose tissue inflammation characterized by adipose tissue macrophage (ATM) infiltration. In this study, we present a novel Drosophila model to investigate the mechanisms underlying ATM infiltration and its association with obesity-related pathologies. Furthermore, we demonstrate the therapeutic potential of attenuating Eiger/TNFα signaling to ameliorate insulin resistance and ATM. To study ATM infiltration and its consequences, we established a novel Drosophila model (OBL) that mimics key aspects of human adipose tissue and allows for investigating ATM infiltration and other related metabolic disorders in a controlled experimental system. We employed genetic manipulation to reduce ecdysone levels to prolong the larval stage. These animals are hyperphagic, and exhibit features resembling obesity in mammals, including increased lipid storage, adipocyte hypertrophy, and high levels of circulating glucose. Moreover, we observed a significant infiltration of immune cells (hemocytes) in the fat bodies accompanied by insulin resistance and systemic metabolic dysregulation. Furthermore, we found that attenuation of Eiger/TNFα signaling and using metformin and anti-oxidant bio-products like anthocyanins led to a reduction in ATM infiltration and improved insulin sensitivity. Our data suggest that the key mechanisms that trigger immune cell infiltration into adipose tissue are evolutionarily conserved and may provide the opportunity to develop Drosophila models to better understand pathways critical for immune cell recruitment into adipose tissue, in relation to the development of insulin resistance in metabolic diseases such as obesity and type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). We believe that our OBL model can also be a valuable tool and provide a platform either to perform genetic screens or to test the efficacy and safety of novel therapeutic interventions for these diseases.


[Effect of processing on the alkaloids in Strychnos nux-vomica L].
The contents of strychnine, brucine, isostrychnine and isobrucine in different processed products of Strychnos nux-vomica were determined by TLC-densitometry. The relationship of the contents of strychnos alkaloids with processing methods was studied.


Focusing on the Fundamentals: A Simplistic Differentiation Between Qualitative and Quantitative Research.
This article describes qualitative, quantitative, and mixed methods research. Various classifications of each research design, including specific categories within each research method, are explored. Attributes and differentiating characteristics, such as formulating research questions and identifying a research problem, are examined, and various research method designs and reasons to select one method over another for a research project are discussed.