Systemic lupus erythematosus presenting initially as hydrogen ATPase pump defects of distal renal tubular acidosis.
Tubulointerstitial involvement is well recognized in systemic lupus erythematosus. The tubular dysfunction is usually latent and usually presents after diagnosis of systemic lupus erythematosus. We report a case presenting that she is well previously and initially diagnosed as periodic paralysis of hypokalemia at emergency room and final diagnosis is systemic lupus erythematosus with H+-ATPase pump defect of distal type renal tubular acidosis. Kidney biopsy showed lupus nephritis classified as mesangial proliferative glomerulonephritis WHO class II B. Her renal tubular acidosis was subsided after steroid therapy was administered.


Empiric medical therapy with hormonal agents for idiopathic male infertility.
Infertility affects approximately 15% of all couples, and male factor contribute to up to 50% of cases. Unfortunately, the cause of male infertility is unknown in about 30% of these cases. Infertility of unknown origin is classified as idiopathic male infertility when abnormal semen parameters are present. Despite not having a definable cause, these men may respond to treatment. This review focuses on the use of empiric hormonal therapies for idiopathic male infertility. A detailed PubMed/MEDLINE search was conducted to identify all publications pertaining to empiric use of hormonal therapies in the treatment of idiopathic male infertility using the keywords "idiopathic," "male infertility," "empiric treatment," "clomiphene," "SERM," "gonadotropin," "aromatase inhibitor," and "androgen." These manuscripts were reviewed to identify treatment modalities and results. Gonadotropins, androgens, aromatase inhibitors, and selective estrogen receptor modulators (SERMs) have all been used with varying results. The studies on these treatments are of variable quality. The most well-studied agents are the SERMs which show a modest increase in semen parameters and pregnancy rates. Aromatase inhibitors are most effective in non-idiopathic patients. Gonadotropin treatment is limited by their inconvenience and relative ineffectiveness in this population. Testosterone suppresses spermatogenesis and should not be used to treat infertility. Gonadotropins, SERMs, and aromatase inhibitors may improve semen parameters and hormone levels in men with idiopathic infertility with the best results from SERMs. Testosterone should never be used to treat infertility. Large multicenter randomized controlled studies are needed to better determine the success of empiric use of hormonal therapy on pregnancy rates.


The selective vulnerability of brainstem nuclei to Alzheimer's disease.
In a study of thioflavin S-stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic, cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with Alzheimer's disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with Alzheimer's disease exhibit either neurofibrillary tangles or senile plaques, and only a few display both. However, when sections were immunostained with the antibodies 10D5 and AT8 or ALZ50, both beta-amyloid and hyperphosphorylated epitopes of tau protein were found to be present in various concentrations in all the affected nuclei. Our findings suggest that each brainstem nucleus has a distinct vulnerability to Alzheimer's disease-related pathological changes. Given that each nucleus has idiosyncratic neuroanatomical connections and prevailing neurochemical characteristics, the heterogeneous collection of brainstem nuclei can be considered a suitable anatomical ground for further investigation of selective vulnerability in Alzheimer's disease. The finding of severe pathological changes in some brainstem nuclei also raises the possibility that the dysfunction of these nuclei may contribute to the cognitive defects and increased rates of morbidity and mortality in patients with Alzheimer's disease.


[The substitution of protein feed by lysine supplemented protein-rich wheat during the raising and laying periods of hens. 7. Report. Determination of the true digestibility of amino acids with and without lysine supplement in the feed].
In the present paper regression techniques were used for determing the true digestibility of amino acids from lysine-supplemented rations fed to laying hens as compared with unsupplemented rations of the same composition. 5 groups of 4 hens each were investigated receiving graded amounts of food and nutrients. The daily amounts of pellets fed per bird in group 1 to 5 were 120 gms, 100 gms, 80 gms, 60 gms and 40 gms. The quantity of lysine contained in 100 gms of the pellets was 664 mg in ration 1 and 554 mg in ration 2, the corresponding N values being 2.57 gm and 2.62 mg. The total amount of endogenic amino acids excreted per day was 128 mg per kg of body weight in birds receiving the lysine-supplemented ration and 132 mg per kg of body weight for the lysine-deficient ration. Data for the true digestibility of lysine and isoleucine were significantly higher in the case of the lysine-supplemented ration than with the lysine-deficient mixture. Lysine values were 86% and 75%, the corresponding lysine data in crude faecal proteins 4.8% and 7.1%. Generally speaking, the crude faecal protein of hens fed the lysine-deficient diet contained higher proportions of most of the essential and non-essential amino acids.


[The beta-adrenoceptor and pathophysiological study on acute lung injury induced by oleic acid in rats].
Sixty male Wistar rats were randomized into six groups. In the control and injury group normal saline and oleic acid were injected in tail veins respectively. Dexamethasone, Salviae mitiorrhizae, Ligustrazini and phenobarbitalum natrium were intraperitoneally for the other four groups 15 minutes before the intravenous injection of oleic acid separately. The results showed that the Bmax of beta-adrenoceptor in injury group were decreased markedly and there was correlation between the decreasing of beta-adrenoceptor numbers and pathologic damage in acute lung injury rat. The Bmax of beta-adrenoceptor in cortisone group were similar to control group, which indicated that cortisone is effective to prevent pathologic damage from lung injury by maintenance of the activity of beta-adrenoceptor.


Dentin permeability reduction by a sequential application of calcium and fluoride-phosphate solutions.
A sequential topical application of calcium and fluoride-phosphate solutions was reported to occlude open dentin tubules, mainly with fluoroapatite precipitates by a rapid ionic reaction, and to be effective at treating dentin hypersensitivity. However, its ability to reduce dentin permeability (Lp) is unknown. The aim of this in vitro study was to evaluate the effect of this treatment on Lp. Nine extracted human third molars were sectioned transversely to obtain 0.5 mm-thick discs, which were then etched and rinsed. Aqueous solutions of 5% (w/w) disodium phosphate containing 0.3% (w/w) sodium fluoride (A) and 10% (w/w) calcium chloride (B) were prepared. The sequential application of the A&B solutions was repeated three times on each disc, which was then rinsed with distilled water. The Lp of the discs was measured before and after the application using a modified Pashley's fluid flow measuring system. The differences in the Lp values between the conditions before and after the solution applications were analysed using a generalized estimating equation method and paired t-test. Scanning Electron Microscopy (SEM) was used to observe the dentin surfaces. All nine discs consistently indicated reduced Lp following the application of the A&B solutions. There was a significant decrease in the mean Lp [microL/(cm(2) s cm H(2)O)] from baseline (-0.27+/-0.25, p=0.011). Overall, an average decrease of 34% Lp occurred after the application of the A&B solutions. SEM observation indicated that the reaction products covered the entire dentin disc surface. The application of the A&B solutions was effective at reducing the Lp of the dentin discs.


[Stages of the development of the embryos of snakes by the time of oviposition].
Embryos of 6 species of snakes--Ptyas mucosus (L.), Elaphe dione (Pall.), Psammophis lineolatum (Brandt), Natrix tesselata (Laur), Naja oxiana (EICHW.), Vipera lebetina turanica (Cernov) and V. l. obtusa--at the stage of egg laying are described morphologically. Different species of snakes are shown to lay the eggs containing embryos of different degrees of maturation. This series of transitions at the embryonic age (up to the time of egg viviparity) is connected with ecological peculiarities of different species.


Electrochemical detection of myeloperoxidase (MPO) in blood plasma with surface-modified electroless nickel immersion gold (ENIG) printed circuit board (PCB) electrodes.
Printed circuit board (PCB) based biosensors have often utilized hard gold electroplating, that nullifies the cost advantages of this technology as compared to screen printed electrodes. Electroless nickel immersion gold (ENIG) is a popular gold deposition process widely used in PCB manufacturing, but vulnerable to pinhole defects and large surface roughness, which compromises biosensor performance. In this work, we present a method to address these challenges through electrodeposition of methylene blue (MB) to cover surface defects and improve electroactivity of ENIG PCB electrodes. We also demonstrate a process to realize in situ synthesis of gold nanoparticles (AuNPs) using acid-functionalized multi-walled carbon nanotubes (MWCNTs) as scaffold, that are used to immobilize antibody for the target molecule (myeloperoxidase: MPO, early warning biomarker for cardiovascular diseases) through a modified cysteamine/gluteraldehyde based process. The processing steps on the electrode surface are developed in a manner that do not compromise the integrity of the electrode, resulting in repeatable and reliable performance of the sensors. Further, we demonstrate a cost-effective microfluidic packaging process to integrate a capillary pump driven microfluidic channel on the PCB electrode for seamless introduction of samples for testing. We demonstrate the ability of the sensor to distinguish clinically abnormal concentrations of MPO from normal concentrations through extensive characterization using spiked serum and blood plasma samples, with a limit of detection of 15.79 ng/mL.


Salmonella enterica serovar Choleraesuis vector outperforms alum as an adjuvant, increasing a cross-protective immune response against Glaesserella parasuis.
The adjuvant and/or vector significantly affect a vaccine's efficacy. Although traditional adjuvants such as alum have contributed to vaccine development, deficiencies in the induction of cellular and mucosal immunity have limited their further promotion. Salmonella vectors have unique advantages for establishing cellular and mucosal immunity due to mucosal pathways of invasion and intracellular parasitism. In addition, Salmonella vectors can activate multiple innate immune pathways, thereby promoting adaptive immune responses. In this work, the attenuated Salmonella enterica serovar Choleraesuis (S. Choleraesuis) vector rSC0016 was used to deliver the conserved protective antigen HPS_06257 of Glaesserella parasuis (G. parasuis), generating a novel recombinant strain rSC0016(pS-HPS_06257). The rSC0016(pS-HPS_06257) can express and deliver the HPS_06257 protein to the lymphatic system of the host. In comparison to HPS_06257 adjuvanted with alum, rSC0016(pS-HPS_06257) significantly increased TLR4 and TLR5 activation in mice as well as the levels of proinflammatory cytokines. In addition, rSC0016 promoted a greater degree of maturation in bone marrow-derived dendritic cells (BMDCs) than alum. The specific humoral, mucosal, and cellular immune responses against HPS_06257 in mice immunized with rSC0016(pS-HPS_06257) were significantly higher than those of HPS_06257 adjuvanted with alum. HPS_06257 delivered by the S. Choleraesuis vector induces a Th1-biased Th1/Th2 mixed immune response, while HPS adjuvanted with alum can only induce a Th2-biased immune response. HPS_06257 adjuvanted with alum only causes opsonophagocytic activity (OPA) responses against a homologous strain (G. parasuis serotype 5, GPS5), whereas rSC0016(pS-HPS_06257) could generate cross-OPA responses against a homologous strain and a heterologous strain (G. parasuis serotype 12, GPS12). Ultimately, HPS_06257 adjuvanted with alum protected mice against lethal doses of GPS5 challenge by 60 % but failed to protect mice against lethal doses of GPS12. In contrast, mice immunized with rSC0016(pS-HPS_06257) had 100 % or 80 % survival when challenged with lethal doses of GPS5 or GPS12, respectively. Altogether, the S. Choleraesuis vector rSC0016 could potentially generate an improved innate immune response and an improved adaptive immunological response compared to the traditional alum adjuvant, offering a novel concept for the development of a universal G. parasuis vaccine.


Parameters of the attenuated schistosome vaccine evaluated in the olive baboon.
Five exposures of baboons to the attenuated schistosome vaccine gave greater protection than three exposures, but this attenuation was not sustained when challenge was delayed. Within the scope of the data collected, fecal egg counts and circulating antigen levels did not accurately predict the observed worm burdens. Levels of immunoglobulin G at challenge correlated best with protection, but there was little evidence of a recall response.


Effects of Cycling and Exergaming on Neurotrophic Factors in Elderly Type 2 Diabetic Men - A Preliminary Investigation.
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing neurodegenerative diseases. There is growing evidence that repeated exercise-induced transient increases in neurotrophic factors can augment neurogenesis and neuroplasticity. This pilot study compares the effects of 30-min submaximal cycling with those of exergaming (combining exercise and video gaming) at the same duration and same rating of perceived exertion (BORG RPE: 14-15) on serum neurotrophic factors in 8 elderly non-insulin-dependent T2DM patients (71±4 years) (2×2 crossover design). Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 levels were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Heart rates were almost equal during cycling and exergaming, while lactate values were significantly higher during cycling (cycling versus exergaming: 3.7±1.1 versus 2.5±1.2 mmol/l, p<0.05). BDNF and VEGF levels were increased significantly post-cycling (+20%,+14%, p<0.05). No other significant pre-post changes were evident. This study demonstrates that acute exercise can increase neurotrophic factors (BDNF, VEGF) in elderly T2DM patients, depending on exercise mode.


Mechanism of action of arginine vasopressin on acute ischemic brain edema.
The purpose of this experiment is to study the role of arginine vasopressin (AVP) in acute cerebral ischemic edema in Mongolian gerbils. The results show that intracerebroventricular injection (ICV) of AVP exacerbates acute ischemic brain edema, while ICV of AVP antiserum significantly decreases the ischemic brain edema. Nimodipine (calcium antagonist) cannot block this role of AVP in brain edema. In addition, the cortical Na(+)-K+ ATPase activity is significantly decreased, while the cAMP content of ischemic cortex and hypothalamus and the cGMP content of the hypothalamus are markedly increased after AVP ICV. These suggest that AVP may play an important role in the pathophysiologic process of ischemic brain edema by inhibiting the Na(+)-K+ ATPase activity of the cerebral cell membrane and the AVP receptors mediated by cAMP and cGMP.


What has finite element analysis taught us about diabetic foot disease and its management? A systematic review.
Over the past two decades finite element (FE) analysis has become a popular tool for researchers seeking to simulate the biomechanics of the healthy and diabetic foot. The primary aims of these simulations have been to improve our understanding of the foot's complicated mechanical loading in health and disease and to inform interventions designed to prevent plantar ulceration, a major complication of diabetes. This article provides a systematic review and summary of the findings from FE analysis-based computational simulations of the diabetic foot. A systematic literature search was carried out and 31 relevant articles were identified covering three primary themes: methodological aspects relevant to modelling the diabetic foot; investigations of the pathomechanics of the diabetic foot; and simulation-based design of interventions to reduce ulceration risk. Methodological studies illustrated appropriate use of FE analysis for simulation of foot mechanics, incorporating nonlinear tissue mechanics, contact and rigid body movements. FE studies of pathomechanics have provided estimates of internal soft tissue stresses, and suggest that such stresses may often be considerably larger than those measured at the plantar surface and are proportionally greater in the diabetic foot compared to controls. FE analysis allowed evaluation of insole performance and development of new insole designs, footwear and corrective surgery to effectively provide intervention strategies. The technique also presents the opportunity to simulate the effect of changes associated with the diabetic foot on non-mechanical factors such as blood supply to local tissues. While significant advancement in diabetic foot research has been made possible by the use of FE analysis, translational utility of this powerful tool for routine clinical care at the patient level requires adoption of cost-effective (both in terms of labour and computation) and reliable approaches with clear clinical validity for decision making.


[Prevalence of gastrointestinal nematodes in sheep in the Sanliurfa region].
In this study, the gastrointestinal nematodes of 75 sheep and their seasonal prevalence were investigated during March 2003-2004, in the Sanliurfa district, in Turkey. Fifty-seven (76 %) of the sheep under investigation were infected with gastro-intestinal nematodes. Eleven nematode species were detected. A total of 2,711 nematodes were collected from the digestive system of the infected sheep. The total number of parasites in each infected animal ranged from 1-977. The average number of parasites in each sheep was found to be 47.5. The number of nematode species in each animal also ranged from 1-5. Most of species in the infected sheep was found to be as follows; Ostertagia marshalli, O. occidentalis, O. circumcincta, N. spathiger, N. filicollis, T. ovis, and T. skrjabini.


Viral infections among couples for assisted reproduction in a fertility clinic in Nigeria.
The risk of laboratory cross-contamination may limit the availability of assisted conception for couples infected with chronic viruses. However, assisted conception is the standard of care for people living with human immunodeficiency virus (HIV) to minimize risk of transmission or reinfection. To assess the burden of viral infection among couples that present for assisted reproductive technology (ART) with a view to evaluating implications for their care. A cross-sectional descriptive study carried out among 138 couples at a private fertility clinic in Nigeria. Screening for HIV, hepatitis B virus (HBV) and hepatitis C virus were carried out among these clients. The males' seminal parameters were analyzed according to World Health Organization (WHO) criteria. Statistical Package for Social Sciences was employed. Analysis was by Chi-square test; statistical significance was set at 0.05. Viral infections were found in 10/138 women (7.2%) and 15/138 (10.9%) men. The most prevalent infection was HBV. Twenty-one couples were sero-discordant. Two couples had concordant HIV and HBV infections, respectively. There was no significant association between sperm quality and chronic hepatitis infection. Nearly a fifth of the couples had at least one partner infected with a chronic virus - a proportion significant enough to demand attention. Apart from separate laboratory and storage facilities, basic principles to minimize transmission are recommended: HBV vaccination in sero-discordant partners of HBV carriers (and immunoprophylaxis for the baby) and antiretroviral therapy for HIV-positive partners to reduce the viral load before fertility treatment is commenced.


Metabolomic characterization of the salt stress response in Streptomyces coelicolor.
The humicolous actinomycete Streptomyces coelicolor routinely adapts to a wide variety of habitats and rapidly changing environments. Upon salt stress, the organism is also known to increase the levels of various compatible solutes. Here we report the results of the first high-resolution metabolomics time series analysis of various strains of S. coelicolor exposed to salt stress: the wild type, mutants with progressive knockouts of the ectoine biosynthesis pathway, and two stress regulator mutants (with disruptions of the sigB and osaB genes). Samples were taken from cultures at 0, 4, 8, and 24 h after salt stress treatment and analyzed by liquid chromatography-mass spectrometry with an LTQ Orbitrap XL mass spectrometer. The results suggest that a large fraction of amino acids is upregulated in response to the salt stress, as are proline/glycine-containing di- and tripeptides. Additionally we found that 5'-methylthioadenosine, a known inhibitor of polyamine biosynthesis, is downregulated upon salt stress. Strikingly, no major differences between the wild-type cultures and the two stress regulator mutants were found, indicating a considerable robustness of the metabolomic response to salt stress, compared to the more volatile changes in transcript abundance reported earlier.


Adhesion prevention in gynaecological surgery.
To review the etiology and incidence of and associative factors in the formation of adhesions following gynaecological surgery. To review evidence for the use of available means of adhesion prevention following gynaecological surgery. Women undergoing pelvic surgery are at risk of developing abdominal and/or pelvic adhesive disease postoperatively. Surgical technique and commercial adhesion prevention systems may decrease the risk of postoperative adhesion formation. The outcomes measured are the incidence of postoperative adhesions, complications related to the formation of adhesions, and further intervention relative to adhesive disease. Medline, EMBASE, and The Cochrane Library were searched for articles published in English from 1990 to March 2009, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, cohort studies, and meta-analyses specifically addressing postoperative adhesions, adhesion prevention, and adhesive barriers. Searches were updated on a regular basis and incorporated in the guideline to March 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care SUMMARY STATEMENTS: 1. Meticulous surgical technique is a means of preventing adhesions. This includes minimizing tissue trauma, achieving optimal hemostasis, minimizing the risk of infection, and avoiding contaminants (e.g., fecal matter) and the use of foreign materials (e.g., talcum powder) when possible. (II-2). 2. The risk of adhesions increases with the total number of abdominal and pelvic surgeries performed on one patient; every surgery needs to be carefully considered in this context. (II-2). 3. Polytetrafluoroethylene (Gore-Tex) barrier is more effective than no barrier or oxidized regenerated cellulose in preventing adhesion formation. (I). 4. Oxidized regenerated cellulose (Interceed) adhesion barrier is associated with a reduced incidence of pelvic adhesion formation at both laparoscopy and laparotomy when complete hemostasis is achieved. Oxidized regenerated cellulose may increase the risk of adhesions if optimal hemostasis is not achieved. (II-2). 5. Chemically modified sodium hyaluronate/carboxymethylcellulose (Seprafilm) is effective in preventing adhesion formation, especially following myomectomies. There is insufficient evidence on the effect of sodium hyaluronate/carboxymethylcellulose on long-term clinical outcomes such as fertility, chronic pelvic pain or small bowel obstruction. (II-2). 6. No adverse effects have been reported with the use of oxidized regenerated cellulose, polytetrafluoroethylene, or sodium hyaluronate/carboxymethylcellulose. (II-1). 7. Various pharmacological agents have been marketed as a means of preventing adhesions. None of these agents are presently available in Canada. There is insufficient evidence for the use of pharmacological agents in preventing adhesions. (III-C). 1. Surgeons should attempt to perform surgical procedures using the least invasive method possible in order to decrease the risk of adhesion formation. (II-1B ). When feasible, for example, a laparoscopic surgical approach is preferable to an abdominal approach, and a vaginal or laparoscopic hysterectomy is preferable to an abdominal hysterectomy. 2. Precautions should be taken at surgery to minimize tissue trauma in order to decrease the risk of postoperative adhesions. These precautions include limiting packing, crushing, and manipulating of tissues to what is strictly required for safe completion of the procedure. (III-B). 3. Surgeons could consider using an adhesion barrier for patients who are at high risk of forming clinically significant adhesions (i.e., patients who have endometriosis or pelvic inflammatory disease or who are undergoing a myomectomy). If there is a risk of ongoing bleeding from the surgical site, oxidized regenerated cellulose (Interceed) should not be used as it may increase the risk of adhesions in this situation. (II-2B).


Yeast Srs2 Helicase Promotes Redistribution of Single-Stranded DNA-Bound RPA and Rad52 in Homologous Recombination Regulation.
Srs2 is a super-family 1 helicase that promotes genome stability by dismantling toxic DNA recombination intermediates. However, the mechanisms by which Srs2 remodels or resolves recombination intermediates remain poorly understood. Here, single-molecule imaging is used to visualize Srs2 in real time as it acts on single-stranded DNA (ssDNA) bound by protein factors that function in recombination. We demonstrate that Srs2 is highly processive and translocates rapidly (∼170 nt per second) in the 3'→5' direction along ssDNA saturated with replication protein A (RPA). We show that RPA is evicted from DNA during the passage of Srs2. Remarkably, Srs2 also readily removes the recombination mediator Rad52 from RPA-ssDNA and, in doing so, promotes rapid redistribution of both Rad52 and RPA. These findings have important mechanistic implications for understanding how Srs2 and related nucleic acid motor proteins resolve potentially pathogenic nucleoprotein intermediates.


Cloning, mapping and RNA analysis of the human methionine synthase gene.
Elevated levels of plasma homocysteine is a risk factor in both birth defects and vascular disease. Methionine synthase (MS) is a cobalamin dependent enzyme which catalyzes methylation of homocysteine to methionine. Impaired MS activity is expected to lead to increased levels of plasma homocysteine. In addition, defects in this gene may underlie the methionine-dependence observed in a number of human tumor cell lines. We describe here the isolation and characterization of the human MS cDNA. It contains an open reading frame of 3798 nucleotides encoding a protein of 1265 amino acids with a predicted molecular mass of 140 kDa. The amino acid sequence of the human MS is 55% identical with that of the Escherichia coli enzyme (METH) and 64% identical with the predicted Caenorhabditis elegans enzyme. Seven peptide sequences derived from purified porcine MS have substantial similarity to the human protein. Northern analysis indicates that the MS RNA is present in a wide variety of tissues. We have mapped the human gene to chromosomal location 1q43, a region found monosomic in individuals with deletion 1q syndrome. The isolation of the MS cDNA will now allow the direct determination of whether mutations in this gene contribute to folate-related neural tube defects, cardiovascular diseases, and birth defects.


Is anterior communicating artery syndrome related to fornix lesions?
Anterior communicating artery (ACoA) syndrome, which may occur after rupture of ACoA aneurysms, consists of anterograde memory problems, executive dysfunctions, confabulations, and personality changes. Recently, the employment of diffusion tensor tractography (DTT) has related ACoA to microstructural lesions in the cingulum and the fornix, but an accurate characterization of these subjects should be provided. We report the clinical and neuropsychological findings of a patient who developed a severe and persistent amnesia together with significant behavioral changes, as well as her imaging results, where the sole evidence of brain damage was that of the fornix demonstrated by DTT. The four-year neuropsychological follow-up of the subject allows exclusion of other causes. This case demonstrates that microstructural lesions of fornix may lead to persistent amnesia, executive impairments, and behavioral changes and contributes to the knowledge of its role in cognition.


Effectiveness and safety of doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads) once daily as add-on therapy to existing topical regimens for the treatment of papulopustular rosacea: results from a community-based trial.
Rosacea is a prevalent inflammatory skin disorder that affects approximately 16 million individuals in the United States. Although its exact etiology is unknown, basic science, histologic evidence, and clinical evidence suggest that it is inflammatory in nature. In this 12-week, open-label, multicenter, community-based, phase 4 trial, we evaluated the anti-inflammatory effects of once daily subantimicrobial-dose doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads) in participants with papulopustular rosacea (PPR) who were receiving topical therapy (metronidazole, azelaic acid, and/ or sodium sulfacetamide-sulfur) at the time of the study entry but whose rosacea symptoms were still present. The primary outcome measure was the change in the investigator global assessment (IGA) score from baseline to end of study (week 12). Secondary outcome measures were changes from baseline to end of study in the clinician erythema assessment (CEA) score, treatment responders (IGA score of clear, near clear), and safety. After week 12, 75.7% of participants in the per-protocol (PP) population had IGA scores of clear or near clear. In addition, there were significant differences in the distribution of baseline and week 12 IGA scores in the PP group (P = .0012). At week 12, most participants (63.6%) had mild CEA scores; the distribution was significantly different from baseline (P = .0407). Only 7% of participants had treatment-related adverse events (AEs), mostly mild or moderate in severity. Thus the 40-mg formulation of doxycycline proved to be effective and well-tolerated in a real-world setting in participants with rosacea who were receiving topical therapy but still experiencing symptoms.


Recombinant inversion chromosomes in phenotypically normal chickens.
Some progeny resulting from interbreeding of individuals heterozygous for a pericentric inversion of chromosome 1 in the chicken have the two complementary types of recombinant chromosomes arising from a single crossing-over within the inverted segment. These individuals are capable of reproduction. Their progeny can have one or the other of the two recombinant chromosomes or, if crossing-over occurs, either a normal or an inversion chromosome.


Treatment of refractory feline sporotrichosis with a combination of intralesional amphotericin B and oral itraconazole.
OBJECTIVE To describe the use of intralesional amphotericin B in localised lesions for the treatment of 26 cats from Rio de Janeiro, Brazil, with sporotrichosis refractory to oral itraconazole. DESIGN Uncontrolled intervention study. METHOD The 26 cats in this study were diagnosed with sporotrichosis, confirmed by isolation of Sporothrix schenckii, and presented residual localised skin lesions refractory to treatment with oral itraconazole for a minimum period of 8 weeks. The animals received weekly applications of intralesional amphotericin B in conjunction with oral itraconazole. In cases of owner unavailability, a maximum of 2 weeks between the infiltrations was accepted. RESULTS Twenty-two (84.6%) of the 26 treated cats achieved clinical remission, 16 (72.7%) of which were cured, and in the remaining six (27.3%) the lesions recurred at the same site. Lack of clinical response was observed in one animal and three owners abandoned treatment. CONCLUSION The proposed therapeutic regimen is an adjunctive treatment option for cats with sporotrichosis presenting as residual skin lesions refractory to itraconazole.


Repeat transurethral manipulation of bulbar urethral strictures is associated with increased stricture complexity and prolonged disease duration.
We examined the association of previous transurethral manipulation with stricture complexity and disease duration among men referred for bulbar urethral reconstruction. We retrospectively reviewed the records of 340 consecutive urethroplasties performed by a single surgeon between July 2007 and October 2010. Only men treated with initial open surgery for bulbar strictures were included in analysis, thus excluding those with hypospadias, lichen sclerosus, pelvic radiation, prior urethroplasty, incomplete data, or pure penile or posterior urethral stenosis. Cases were divided into 2 groups based on the history of transurethral treatment for urethral stricture before urethroplasty, including group 1-0 or 1 and group 2-2 or greater treatments. Of 101 patients with bulbar urethral stricture and all data available 50 and 51 underwent 0 to 1 and 2 or greater previous transurethral treatments, respectively. Repeat transurethral manipulation was strongly associated with longer strictures and the need for complex reconstruction. Repeat transurethral manipulation of bulbar urethral strictures was also associated with an eightfold increase in disease duration between stricture diagnosis and curative urethroplasty. Repeat transurethral manipulation of bulbar strictures is associated with increased stricture complexity and a marked delay to curative urethroplasty.


Perichondritis of the auricle and its management.
To conduct a study of patients presenting with perichondritis of the auricle and to analyse the possible aetiological factors responsible, the bacteriological agents involved, the treatment modalities and the complications of such infections. Academic department of otolaryngology. A retrospective clinical study of patients treated over a five-year period. Sixty-one patients with clinically proven perichondritis of the auricle, with or without diabetes mellitus (i.e. malignant otitis externa). Based on the severity of the disease, otherwise uncomplicated patients were assigned to group A and divided into three cohorts. Patients with perichondritis secondary to malignant otitis externa were analysed separately as group B. Men formed the majority of the patients and most were young (16-35 years). Trauma was the main cause (46 per cent) and Pseudomonas aeruginosa the most common micro-organism isolated. The condition was managed conservatively with antibiotics alone in 19 patients (31 per cent) and these cases had no residual deformity at follow up (group A, stage one). Incision and drainage was performed in a further 19 patients (31 per cent), resulting in minor residual deformity in one half (group A, stage two). Debridement was performed in 17 patients, and these patients had either gross (29 per cent) or minor residual deformity (71 per cent; group A, stage three). Six patients with perichondritis secondary to malignant otitis externa were managed by wound debridement via a post-auricular approach; all had minor residual deformities. Perichondritis can be divided into two groups, depending on cartilage loss and on the presence or absence of malignant otitis externa. The treatment used and the residual deformity that will ensue are entirely dependent on the stage of disease.


A Randomized Clinical Trial Evaluating Indigo Carmine as a Visualization Aid for Evaluating Ureteral Patency.
To determine whether intravenous indigo carmine provides a visualization advantage compared to saline in the evaluation of ureteral patency in a randomized, controlled clinical trial. Patients undergoing urological or gynecological surgical procedures in which the patency of the ureter was to be assessed received a saline injection and were randomized to receive 2.5 mL or 5.0 mL of indigo carmine. Blinded video assessments were conducted by independent reviewers using a conspicuity scale ranked 1 (poorest) to 5 (best), and subjects with scores ≥ 3 and at least a +1-point difference from saline were considered responders. Time to visualization was recorded for indigo carmine. A responder analysis evaluated whether indigo carmine showed improved visualization. There were 96 ureters evaluated with the 5.0 mL dose of indigo carmine, 92 with the 2.5 mL dose, and 180 with saline. Most ureters were scored a 4 or higher on the conspicuity scale following indigo carmine; both doses were significantly better than saline (p<0.0001). Overall, 92.3% of patients were rated as a responder for either ureter. The median time to visualization of blue color was not significantly different (6.0 minutes in the 5.0 mL group and 5.9 minutes in the 2.5 mL group). There were no adverse events related to indigo carmine use. Both dose levels of indigo carmine were significantly better than saline as a visualization aid for ureter patency.


Morphometric quantitation of the pancreatic insulin-, glucagon-, and somatostatin-positive cell populations in normal and alloxan-diabetic rats.
The pancreatic insulin-, glucagon-, and somatostatin-positive cell populations were quantitated in normal and alloxan-diabetic rats. The method of quantitation (linear scanning) allowed an estimation of absolute changes in these cell populations through 14 months of diabetes. The changes in cell masses were correlated with changes in plasma and pancreatic immunoreactive insulin and glucagon. A marked reduction in the insulin-positive beta cells was demonstrated within seven days after alloxan treatment. No significant change in the glucagon-positive alpha cell population was noted in the diabetic rats when compared with normoglycemic controls. A statistically significant increase in the pancreatic somatostatin-positive delta cell population was demonstrable only after 14 months of alloxan diabetes. The results would suggest that the hyperglucagonemia of insulin-deficient diabetes is not a consequence of an increased pancreatic alpha cell population. In addition, since the increase in the pancreatic delta cell mass was found only late in the course of alloxan diabetes in the rat, the increase in delta cells is probably not of significance in the pathophysiology of diabetes in this experimental model.


Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.
One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 was fabricated by mixing two reverse microemulsions containing KCl solution and a highly soluble cis-diaminedihydroplatinum (II) coated with a cationic lipid layer. Subsequently, the miR-375 was incorporated into the lipid-coated cisplatin nanoparticles. The NPC/miR375 nanoparticles were expected to further decrease cell proliferation and to enhance the anti-tumor effect of cisplatin in chemotherapy resistant HCC cells. In vitro analysis of intracellular trafficking revealed that NPC/miR-375 were able to escape from the late endosomes instead of lysosomes thus avoiding degradation of the miR-375 in lysosomes. Importantly, NPC/miR-375 enhanced apoptosis and induced cell cycle arrest in HCC cells in vitro. In the double oncogenes Akt/Ras-induced primary HCC mouse model, multiple doses of NPC/miR-375 significantly inhibited tumor growth and delayed the tumor relapse. Our results indicate that cisplatin nanoparticles co-loaded with miR-375 represent a potential therapeutic agent for chemotherapy-insensitive HCC.


Toll-like receptor 4 regulates platelet function and contributes to coagulation abnormality and organ injury in hemorrhagic shock and resuscitation.
Growing evidence indicates that the presence of toll-like receptor 4 (TLR4) on platelets is a key regulator of platelet number and function. Platelets exposed to TLR4 agonists may serve to activate other cells such as neutrophils and endothelial cells in sepsis and other inflammatory conditions. The functional significance of platelet TLR4 in hemorrhagic shock (HS), however, remains unexplored. Using thromboelastography and platelet aggregometry, we demonstrate that platelet function is impaired in a mouse model of HS with resuscitation. Further analysis using cellular-specific TLR4 deletion in mice revealed that platelet TLR4 is essential for platelet activation and function in HS with resuscitation and that platelet TLR4 regulates the development of coagulopathy after hemorrhage and resuscitation. Transfusion of TLR4-negative platelets into mice resulted in protection from coagulopathy and restored platelet function. Additionally, platelet-specific TLR4 knockout mice were protected from lung and liver injury and exhibited a marked reduction in systemic inflammation as measured by circulating interleukin-6 after HS with resuscitation. We demonstrate for the first time that platelet TLR4 is an essential mediator of the inflammatory response as well as platelet activation and function in HS and resuscitation.


A novel GBA2 gene missense mutation in spastic ataxia.
Autosomal recessive cerebellar ataxias (ARCA) encompass a heterogeneous group of rare diseases that affect the cerebellum, the spinocerebellar tract and/or the sensory tracts of the spinal cord. We investigated a consanguineous Cypriot family with spastic ataxia, aiming towards identification of the causative mutation. Family members were clinically evaluated and studied at the genetic level. Linkage analysis at marker loci spanning known ARCA genes/loci revealed linkage to the APTX locus. Thorough investigation of the APTX gene excluded any possible mutation. Whole genome linkage screening using microsatellite markers and whole genome SNP homozygosity mapping using the Affymetrix Genome-Wide Human SNP Array 6.0 enabled mapping of the disease gene/mutation in this family to Chromosome 9p21.1-p13.2. Due to the large number of candidate genes within this region, whole-exome sequencing of the proband was performed and further analysis of the obtained data focused on the mapped interval. Further investigation of the candidate variants resulted in the identification of a novel missense mutation in the GBA2 gene. GBA2 mutations have recently been associated with hereditary spastic paraplegia and ARCA with spasticity. We hereby report a novel GBA2 mutation associated with spastic ataxia and suggest that GBA2 mutations may be a relatively frequent cause of ARCA.


Visualizing a set of olfactory sensory neurons responding to a bile salt.
In the present study, we exposed the olfactory epithelia of crucian carp, Carassius carassius, and brown trout, Salmo trutta, to dextran coupled with Alexa dyes together with odorants. Dye uptake was severely reduced after pre-exposure to nocodazole, an inhibitor of microtubule polymerization that impairs endocytosis, supporting the hypothesis that odour-activated olfactory receptor molecules undergo endocytosis. Application of the bile acid taurolithocholate, a potent and specific odorant for fish, resulted in the labelling of a sparse (less than 3%) cell population with the typical morphology of ciliated sensory neurons (CSNs) - long dendrites and cell somata deep in the sensory epithelium. The dye was distributed throughout the sensory neuron, also revealing axons and target glomeruli. Stained axons redistribute at the entrance of the olfactory bulb and terminate in two small target areas, a dorsal and a medial one. These results are consistent with the notion that taurolithocholate is detected specifically by a few ciliated sensory neurons. Application of the olfactory epithelium of brown trout to bile acid stained cells with the appearance of CSNs. Application of an alarm agonist, hypxanthine-3-N-oxide, to crucian carp olfactory organ caused staining of another set of sensory neurons. Furthermore, our results show that odour-induced uptake of a dye can serve to identify the subtype of olfactory sensory neurons responding to a particular odorant, and to pinpoint the target regions of these neurons in the olfactory bulb as a first step to elucidating the neuronal network responding to a particular odour.


Patch size and distance: modelling habitat structure from the perspective of clonal growth.
This study considers the spatial structure of patchy habitats from the perspective of plants that forage for resources by clonal growth. Modelling is used in order to compare two basic strategies, which differ in the response of the plant to a patch boundary. The 'avoiding plant' (A) never grows out of a good (resource-rich) patch into a bad (resource-poor) region, because the parent ramet withdraws its subsidy from the offspring. The 'entering plant' (E) always crosses the boundary, as the offspring is subsidized at the expense of the parent. In addition to these two extreme scenarios, an intermediate mixed strategy (M) will also be tested. The model is used to compare the efficiency of foraging in various habitats in which the proportion of resource-rich areas (p) is varied. A stochastic cellular automata (CA) model is developed in which habitat space is represented by a honeycomb lattice. Each cell within the lattice can accommodate a single ramet, and colonization can occur from a parent ramet's cell into six neighbouring cells. The CA consists of two layers: the population layer and the habitat. In the population layer, a cell can be empty or occupied by a ramet; in the habitat layer, a cell can be good (resource-rich) or bad (resource-poor). The habitat layer is constant; the population layer changes over time, according to the birth and death of ramets. Strategies M and E are primarily limited by patch distance, whereas A is more sensitive to patch size. At a critical threshold of the proportion of resource-rich areas, p = 0·5, the mean patch size increases abruptly. Below the threshold, E is more efficient than A, whilst above the threshold the opposite is true. The mixed strategy (M) is more efficient than either of the pure strategies across a broad range of p values. The model predicts more species/genotypes with the 'entering' strategy, E, in habitats where resource-rich patches are scattered, and more plants with the 'avoiding' strategy, A, in habitats where the connectivity of resource-rich patches is high. The results suggest that the degree of physiological integration between a parent and an offspring ramet is important even across a very short distance because it can strongly influence the efficiency of foraging.


Standardizing the 60-second hair count.
To define the range of normal for a standardized 60-second hair count in men without alopecia. Convenience sample. Hospital-based practice. The study included 60 healthy men (age range, 20-60 years) without evidence of alopecia. Range of normal for a standardized 60-second hair count. Among the 20- through 40-year-old men, the shedding range was 0 to 78 hairs, with a mean of 10.2 hairs. Among the 41- through 60-year-old men, the range was 0-43 hairs, with a mean of 10.3 hairs. Low intrapatient variability for hair counts was found in both age groups, indicating consistent results on consecutive days for all participants. When repeated 6 months later in both age groups, the hair counts did not change much. The hair counts were repeated and verified by a trained investigator, with results similar to those of subject hair counts. A properly performed 60-second hair count is a simple, practical, and reliable tool for the assessment of hair shedding.


Efficient implementation of restricted active space configuration interaction with the hole and particle approximation.
The restricted active space configuration interaction (RASCI) formalism with the hole and particle truncation of the wavefunction, that is, RASCI(h,p), holds very nice properties such as balanced treatment of ground and low-lying excited states, spin-completeness, large flexibility of the wavefunction, and moderate computational cost. In this article, I present a new implementation of the RASCI(h,p) method using a general algorithm based on the integral-driven approach. The new implementation allows to choose any electronic configuration as the single reference in combination with an excitation operator with any number of ionization, electron attachment, or spin-flip (SF) excitations. The applicability and good performance of the new computational code is tested in the ground state calculation of water molecule with increasingly large active spaces and up to the full-CI limit, the calculation of all-trans linear polyenes with variable number of SF excitations, and the low-lying states of fluorine molecule with a double-ionization potential operator.


To be or not to be fragrant: floral scent of some bat-pollinated cacti.
Floral scent is a key olfactory cue in both diurnal and nocturnal pollination systems. In the case of nocturnal systems, such as bat-pollinated flowers, odour seems to play a more important role than visual cues. Cactaceae include many bat-pollinated species; however, few studies have investigated the olfactory cues in this family. We analysed and compared the chemical composition of the floral bouquet of three chiropterophilous cactus species, among which are a pair of congeners that differ considerably in scent intensity. Our research presents novel findings regarding the floral scent chemistry of chiropterophilous cactus species. We documented the first case of a bat-pollinated cactus whose flowers lack perceptible floral scent and in which no volatile compounds were detected in our chemical analyses. Additionally, we provide a comprehensive analysis of the chemical composition of the floral bouquet of the other two bat-pollinated species, revealing a resemblance among closely related species within the same genus. We highlight the need for further studies using biotests to investigate the mechanisms through which bats find flowers lacking scent.


Nanobiotechnology: protein-nanomaterial interactions.
We review recent research that involves the interaction of nanomaterials such as nanoparticles, nanowires, and carbon nanotubes with proteins. We begin with a focus on the fundamentals of the structure and function of proteins on nanomaterials. We then review work in three areas that exploit these interactions: (1) sensing, (2) assembly of nanomaterials by proteins and proteins by nanomaterials, and (3) interactions with cells. We conclude with the identification of challenges and opportunities for the future.


Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster.
Mutations in PINK1 and Parkin cause familial, early onset Parkinson's disease. In Drosophila melanogaster, PINK1 and Parkin mutants show similar phenotypes, such as swollen and dysfunctional mitochondria, muscle degeneration, energy depletion, and dopaminergic (DA) neuron loss. We previously showed that PINK1 and Parkin genetically interact with the mitochondrial fusion/fission pathway, and PINK1 and Parkin were recently proposed to form a mitochondrial quality control system that involves mitophagy. However, the in vivo relationships among PINK1/Parkin function, mitochondrial fission/fusion, and autophagy remain unclear; and other cellular events critical for PINK1 pathogenesis remain to be identified. Here we show that PINK1 genetically interacted with the protein translation pathway. Enhanced translation through S6K activation significantly exacerbated PINK1 mutant phenotypes, whereas reduction of translation showed suppression. Induction of autophagy by Atg1 overexpression also rescued PINK1 mutant phenotypes, even in the presence of activated S6K. Downregulation of translation and activation of autophagy were already manifested in PINK1 mutant, suggesting that they represent compensatory cellular responses to mitochondrial dysfunction caused by PINK1 inactivation, presumably serving to conserve energy. Interestingly, the enhanced PINK1 mutant phenotype in the presence of activated S6K could be fully rescued by Parkin, apparently in an autophagy-independent manner. Our results reveal complex cellular responses to PINK1 inactivation and suggest novel therapeutic strategies through manipulation of the compensatory responses.


Nanosystem trends in drug delivery using quality-by-design concept.
Quality by design (QbD) has become an inevitable trend because of its benefits for product quality and process understanding. Trials have been conducted using QbD in nanosystems' optimization. This paper reviews the application of QbD for processing nanosystems and summarizes the application procedure. It provides prospective guidelines for future investigations that apply QbD to nanosystem manufacturing processes. Employing the QbD concept in this way is a novel area in nanosystem quality.


Protein degradation in rumen and amino acid absorption in small intestine of lactating dairy cattle fed heat-treated whole soybeans.
Four lactating Holstein cows fitted with rumen cannulae and T-type cannulae in proximal duodenum and terminal ileum were used to measure protein degradation in the rumen and amino acid flow and absorption in the small intestine. Soybean meal, whole soybeans, and whole soybeans extruded at 132 and 149 degrees C provided 50% of the protein in diets that contained 51% grain, 36% corn silage, and 13% alfalfa hay (dry matter). Spot samples of digesta were collected from duodenum and ileum during 96 h, and lanthanum was an indigestible marker to estimate flow and digestibility of nutrients. With diaminopimelic acid as a microbial marker, apparent degradations of dietary crude protein in the rumen were 73, 80, 66, and 60% for diets containing soybean meal, whole soybeans, and whole soybeans extruded at 132 and 149 degrees C. Because of the extensive degradation of protein with the raw soybean diet, less total amino acids reached the duodenum, and because of decrease of availability, absorption from the small intestine (g/day) was lowest with this diet. Feeding diets containing extruded whole soybeans increased availability of total essential amino acids in the small intestine compared with diets containing soybean meal and whole soybeans. Absorption from the small intestine (g/day and percent entering) of individual amino acids was generally higher for extruded whole soybean diets.


Association between high serum blood glucose lymphocyte ratio and all-cause mortality in non-traumatic cerebral hemorrhage: a retrospective analysis of the MIMIC-IV database.
This study aimed to evaluate the association between the glucose-to-lymphocyte ratio (GLR) and all-cause mortality in intensive care unit (ICU) patients with Non-traumatic cerebral hemorrhage. This is a retrospective cohort study. Baseline data and in-hospital prognosis from patients with non-traumatic cerebral hemorrhage admitted to the intensive care unit. Multivariate COX regression analysis was applied and adjusted hazard ratios (HR) and 95% predictive values with confidence intervals (CI) were calculated. Survival curves for the two groups of cases were plotted using K-M curves, and subgroup analyses were performed in one step. Using restricted cubic spline curves, we analyzed the potential linear relationship between GLR and outcome indicators. In the Medical Information Mart for Intensive Care IV (MIMIC-IV database), we extracted 3,783 patients with nontraumatic intracerebral hemorrhage, and 1,806 patients were finally enrolled in the study after exclusion of missing values and patients with a short hospital stay. The overall ICU mortality rate was 8.2% (148/1806) and the in-hospital mortality rate was 12.5% (225/1806). The use of curve fitting yielded a significant linear relationship between GLR and both ICU mortality and in-hospital mortality. It also suggested a reference point at GLR=3.9. These patients were categorized into high and low subgroups based on the median value of their GLR (GLR = 3.9). Model comparisons based on multivariate COX regression analysis showed that in-hospital mortality was higher in the high GLR group after adjusting for all confounders (HR = 1.31, 95% CI: 1.04-1.47), while the ICU mortality in the high GLR group was (HR = 1.73, 95% CI: 1.18-2.52). Stratified analyses based on age, gender, race, GCS, BMI, and disease type showed stable correlations between the high GLR group and in-hospital and ICU mortality. Based on our retrospective analysis, it is known that as the GLR increased, the in-hospital mortality rate and ICU mortality rate of patients with nontraumatic cerebral hemorrhage also increased progressively in the United States in a clear linear relationship. However, further studies are needed to confirm these findings.


Molecular characterization and phylogenetic analysis of full-genome HBV subgenotype D3 sequences from Serbia.
Hepatitis B virus (HBV) is classified into 8 genotypes with distinct geographical distribution. Genotype D (HBV/D) has the widest distribution area and is comprised of 7 subgenotypes. Subgenotypes D1, D2 and D3 appear worldwide, while D4-D7 have a more restricted distribution. Within the Mediterranean area, HBV/D and subgenotype D3 are the most prevalent. The purpose of this study was to characterize the full genome of Serbian HBV/D3 isolates by comparison and phylogenetic analysis with HBV/D3 sequences (66 samples) found in GeneBank/DDBJ databases from different parts of the world. Isolates were obtained from three patients diagnosed with chronic hepatitis B (HBsAg+). All three isolates have two very rare nucleotide substitutions, A929T and T150A, which indicate the same ancestor. Phylogenetic analysis of HBV/D3 genome sequences throughout the world follows an ethno-geographical origin of isolates with rare exceptions, which could be explained by human travelling and migration. The geographically close but ethnically different Serbian and Italian isolates clustered in the same subnode, and on a common branch with strains from Northern Canada. To test the apparently close HBV phylogenetic relationship between completely separated patients from Serbia and Northern Canada we analyzed in depth a 440 bp region of the HBsAg from Canadian (n=73) and Serbian (n=70) isolates. The constructed parsimony tree revealed that strains from Serbia and Northern Canada fell along the same branch which indicates independent evolution within regions of each country. Considering that HBsAg sequence has limited variability for phylogenetic analyses, our hypothesis needs further confirmation with more HBV complete genome sequences.


Prostate specific antigen assay standardization bias could affect clinical decision making.
Although prostate specific antigen is widely used to detect and manage prostate cancer, many patients and physicians are unaware of which prostate specific antigen assay is being used. Most commercial prostate specific antigen assays are standardized to the WHO 90:10 standard or aligned with the original Hybritech assay with potentially disparate results. A total of 1,916 men participated in a prostate cancer screening study in 2007. On the day of collection prostate specific antigen was tested from the same serum sample using the Access (Hybritech standard) and ADVIA Centaur (WHO 90:10 prostate specific antigen standard) assays. We examined the differences between the 2 assays and the effect that this might have on clinical decisions. Median prostate specific antigen was 0.9 and 1.05 ng/ml for the Centaur and Access assays, respectively, representing a 17% difference. Mean prostate specific antigen was 3.45 and 4.79 ng/ml, respectively, representing a 38% difference. Using a prostate specific antigen threshold of 2.5 ng/ml 5% of men would have been recommended to undergo biopsy using the Access but not the Centaur assay. Furthermore, prostate specific antigen differed by greater than 0.4 ng/ml in 26%, greater than 0.75 ng/ml in 14.5% and greater than 2 ng/ml in 4.5% of men in the same sample simply by using the different assays. In our prospective screening population median prostate specific antigen was 17% lower using WHO vs Hybritech based assay standardization. As such, if these assays were instead used on a serial basis in the same patient, this could lead to false acceleration or false deceleration in prostate specific antigen velocity. Thus, the assay may influence the likelihood of prostate biopsy and, thereby, prostate cancer detection.


Effect of pimecrolimus cream 1% on the long-term course of pediatric atopic dermatitis.
This report investigates the effect of pimecrolimus cream 1% (Elidel, Novartis pharma AG, Basel, Switzerland), a nonsteroid, cell-selective, cytokine inhibitor on the course of atopic dermatitis (AD), as assessed by changes in body surface involvement and pattern of drug use over time. Data from 961 patients in two 1-year double-blind, multicenter, pediatric studies of similar design were analyzed: 250 infants (aged 3-23 months) were randomized 4 : 1 and 711 children (aged 2-17 years) were randomized 2 : 1 to receive pimecrolimus cream 1% or vehicle, respectively. Emollients were used by all patients to alleviate dry skin and, at the first signs or symptoms of AD, pimecrolimus or vehicle was applied twice daily to prevent progression to flares. If flares occurred in either group, moderately potent topical corticosteroids were mandated. Pimecrolimus was applied for 68.4% (infants) and 53.8% (children) of study days, and frequency of use of pimecrolimus decreased over time, reflecting improvement in disease control. The mean total body surface area affected decreased continuously over time. Significantly more patients in the pimecrolimus than control groups were maintained without corticosteroid therapy (infants: 63.7% vs. 34.8%, P < 0.001; children: 57.4% vs. 31.6%, P < 0.001, respectively). The need for pimecrolimus therapy decreases over time as the patients' disease improves. Hence, once long-term management of AD with pimecrolimus is established, the burden of disease for both the patient and the caregiver decreases significantly and disease-free periods become more frequent.


The dynamic relationship between physical function and cognition in longitudinal aging cohorts.
On average, older people remember less and walk more slowly than do younger persons. Some researchers argue that this is due in part to a common biologic process underlying age-related declines in both physical and cognitive functioning. Only recently have longitudinal data become available for analyzing this claim. We conducted a systematic review of English-language research published between 2000 and 2011 to evaluate the relations between rates of change in physical and cognitive functioning in older cohorts. Physical functioning was assessed using objective measures: walking speed, grip strength, chair rise time, flamingo stand time, and summary measures of physical functioning. Cognition was measured using mental state examinations, fluid cognition, and diagnosis of impairment. Results depended on measurement type: Change in grip strength was more strongly correlated with mental state, while change in walking speed was more strongly correlated with change in fluid cognition. Examining physical and cognitive functioning can help clinicians and researchers to better identify individuals and groups that are aging differently and at different rates. In future research, investigators should consider the importance of identifying different patterns and rates of decline, examine relations between more diverse types of measures, and analyze the order in which age-related declines occur.


Coenzyme Q10 Activates the Antioxidant Machinery and Inhibits the Inflammatory and Apoptotic Cascades Against Lead Acetate-Induced Renal Injury in Rats.
The kidney is among the metabolic organs most susceptible to injury, particularly following exposure to xenobiotics and heavy metals. We aimed to explore the potential protective impacts of coenzyme Q10 (CoQ10) on lead acetate (PbAc)-induced nephrotoxicity in rats. Four experimental groups (n = 7) were applied as follows: control group, CoQ10 alone (10 mg/kg), PbAc alone (20 mg/kg), and PbAc with CoQ10. Exposure to PbAc led to the accumulation of Pb in the kidney and increased urea and creatinine serum levels. The deposition of Pb coupled with the elevation of malondialdehyde and nitrate/nitrite levels along with the upregulation of inducible nitric oxide synthase. Additionally, upon PbAc poisoning, glutathione content and the antioxidant enzymes were depleted along with the downregulation of Nrf2 and HO-1 expression. Moreover, PbAc injection increased the protein and mRNA levels of pro-inflammatory cytokines namely, tumor necrosis factor-alpha and interleukin-1 beta, while decreased the levels of interleukin-10, an anti-inflammatory cytokine, in the kidney. Furthermore, exposure to PbAc correlated with increased levels of pro-apoptotic markers, Bax and caspase-3, and reduced levels of the anti-apoptotic marker Bcl-2. The administration of CoQ10 alleviated the molecular, biochemical and histological changes following PbAc intoxication. Thus, CoQ10 reduces the deleterious cellular side effects of PbAc exposure due to its antioxidant, anti-inflammatory and anti-apoptotic effects.


Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation.
Colonization of mucosal surfaces is the key initial step in most bacterial infections. One mechanism protecting the mucosa is the rapid shedding of epithelial cells, also termed exfoliation, but it is unclear how pathogens counteract this process. We found that carcinoembryonic antigen (CEA)-binding bacteria colonized the urogenital tract of CEA transgenic mice, but not of wild-type mice, by suppressing exfoliation of mucosal cells. CEA binding triggered de novo expression of the transforming growth factor receptor CD105, changing focal adhesion composition and activating beta1 integrins. This manipulation of integrin inside-out signaling promotes efficient mucosal colonization and represents a potential target to prevent or cure bacterial infections.


Synaptic- and agonist-induced excitatory currents of Purkinje cells in rat cerebellar slices.
1. Postsynaptic currents originating from activation of the two major excitatory inputs to Purkinje cells were studied in thin slices of rat cerebellum, using the tight-seal whole-cell recording technique. Two types of excitatory postsynaptic currents were analysed: those evoked by stimulation of the granule cell-parallel fibre system (PF-EPSC) and those elicited by stimulation of the climbing fibres (CF-EPSC). 2. Both types of postsynaptic currents had a linear current-voltage relation, reversing at membrane potentials close to 0 mV. Their time course of activation was independent of the membrane potential. 3. For both types of postsynaptic currents, the time course of decay was well described by a single exponential function, with a time constant which increased as the membrane potential was made more positive. 4. Postsynaptic currents arising from stimulation of the climbing fibre generally had a slightly faster time course of onset and decay than those associated with stimulation of the granule cell-parallel fibre system. The average values of the 10-90% rise time were 1.8 +/- 0.4 ms (means +/- S.D., n = 7) for PF-EPSCs and 0.8 +/- 0.3 ms (n = 9) for CF-EPSCs. Time constants of decay, at a holding potential of -60 mV, had values of 8.3 +/- 1.6 ms (n = 7) and 6.4 +/- 1.1 ms (n = 9) for PF-EPSCs and CF-EPSCs respectively. 5. CF-EPSCs and PF-EPSCs had the characteristics described above in slices derived from animals aged 9-22 days old and 9-15 days old, respectively. The PF-EPSCs in animals older than 15 days had very slow time courses and positive apparent reversal potentials, suggesting that they originated from distal locations, not under accurate voltage control. 6. In order to assess the quality of the voltage clamp, responses to hyperpolarizing pulses from -70 mV were analysed. The capacitive currents could be fitted by the sum of two exponentials, and were interpreted with an equivalent electrical circuit comprising two main compartments (soma and proximal dendrites on one hand, distal dendrites on the other). Analysis of synaptic currents in terms of this model suggested that the recorded time course of decay was approximately correct. 7. CF-EPSCs as well as PF-EPSCs were insensitive to the NMDA receptor antagonist 3-3(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP), but were blocked in a dose-dependent reversible manner by the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX).(ABSTRACT TRUNCATED AT 400 WORDS)


An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machinery.
Serum- and glucocorticoid-induced kinase 1 (Sgk1) regulates many ion channels and transporters in epithelial cells and promotes cell survival under stress conditions. In this study we demonstrate that Sgk1 is a short-lived protein regulated by the endoplasmic reticulum (ER)-associated degradation system and subcellular localization to the ER. We identified a hydrophobic motif (residues 18-30) as the signal for ER localization and rapid degradation by the ubiquitin (Ub)/proteasome pathway in both yeast and mammalian cells. Deletion or reduction of hydrophobicity of the motif redistributes Sgk1 to the cytosol and nucleus and markedly increases its half-life. We determined that the Ub-conjugating UBC6 and UBC7 and the Ub ligase HRD1 are the ER-associated Ub enzymes that mediate degradation of Sgk1; thus, Sgk1 has been identified as a cytosolic substrate for mammalian HRD1. Compartmentalization of Sgk1 controls the functional and spatial specificities of Sgk1-mediated signaling pathways, whereas rapid protein turnover provides a means to rapidly adjust Sgk1 abundance in response to different hormonal and external stimuli that increase Sgk1 gene transcription.


Primary fallopian tube carcinoma: a retrospective clinicopathologic study.
Primary fallopian tube carcinoma is a rare tumor. The aim of this study was to evaluate clinical characteristics and management of fallopian tube malignancies at a large tertiary care cancer institute. A retrospective review of the Tumor Registry was conducted to identify all primary fallopian tube carcinomas between 1980 and 2001. Medical charts were retrospectively reviewed. Primary endpoints were overall survival and disease recurrence. Thirty-five patients had histology consistent with fallopian tube carcinoma. The median age at diagnosis was 56 years. The most common signs or symptoms were abnormal vaginal bleeding (29%) and abdominal/pelvic mass (26%). The most common histology was adenocarcinoma in 16 (46%) patients. Five patients (14%) were Stage I, seven patients (20%) Stage II, 17 patients (49%) Stage III and six patients (17%) Stage IV. Thirty-two (91%) patients received adjuvant chemotherapy and 77% received platinum-based chemotherapy. Twenty-seven (77%) patients underwent second-look surgery, of which 17 patients (63%) were positive for disease. The 5-year survival rate was 64% for Stage I, 42% for Stage II, 32% for Stage III, and 17% for Stage IV. Fallopian tube malignancies are rare and carry a poor prognosis. More extensive research needs to be performed to have definitive etiologic, diagnostic and treatment guidelines.


Endometriosis of Diaphragm: A Case Report.
Endometriosis affects about 10% of women of reproductive age. Its main feature is the presence of stroma and endometrial glands in sites other than the uterus, mainly in pelvis. Pelvic peritoneum, ovaries, uterine ligaments, bladder, intestines, andcul-de-sac are among the affected areas. Sometimes endometriosis can be found outside of the pelvis and even above abdominal cavity, like indiaphragm.Herein, we present a case of an asymptomatic diaphragmatic endometriosis that was discovered incidentally during laparoscopy of pelvic endometriosis, as well as our appropriately proposed treatment protocol.


[Carbonate mineral baths in the combined treatment at a piedmont health resort of patients operated on for rheumatic heart defects].
The response of the cardiovascular system of 64 patients operated for rheumatic heart disease to mineral carbon dioxide baths was studied in the course of rehabilitation in low-mountain health resort. It was found that the above baths have a training effect on the cardiac muscle, improve myocardial metabolism. They are an essential factor in combined sanatorium treatment of patients after surgical correction of valvular defects. Baths-induced changes in the central and peripheral hemodynamics depend on cardiovascular function. Therefore, they require an individual approach. If the exposition increases to 15 minutes, mineral carbon dioxide baths have more potent training effect on the myocardium and raise effectiveness of the sanatorium treatment.


FAK-Src-paxillin system expression and disease outcome in human neuroblastoma.
Neuroblastoma (NB) often presents with metastatic disease and poor survival. The need for new prognostic markers remains invaluable. The FAK-Src-Paxillin protein system is associated with aggressive phenotype in adult malignancies but is largely unexplored in pediatric NB. To assess FAK-Src-Paxillin protein expression in human NB cell lines and clinical cytology material and to delineate its association with survival. Western blot and immunohistochemistry were applied for FAK-Src-Paxillin expression in NB cell lines and 23 human cytology specimens, respectively. Protein expression in human clinical samples was correlated with clinicopathological parameters, MYCN amplification and survival. FAK, Src and Paxillin proteins are expressed in human NB cells lines, and can be detected in clinical cytology specimens from NB patients, (59%, 32% and 33% respectively). Simultaneous FAK-Src-Paxillin expression was noted in 30% of NB patients. Children with concomitant positivity FAK, Src, and Paxillin tumors, as well as MYCN amplification, had increased mortality compared to those without. FAK-Src-Paxillin system is a marker of unfavorable prognosis for human NB patients but also a promising therapeutic target.


[Cross-cultural adaptation and evidence of psychometric validity of the Family Health Scale for Brazilian Portuguese].
This study aimed to translate and cross-culturally adapt the Family Health Scale into Brazilian Portuguese and analyze evidence of its psychometric validity. The 32 items on family health were cross-culturally adapted, using the content validity index to calculate semantic, idiomatic, cultural, and conceptual characteristics of the scale and its items. A pre-test to identify evidence of validity was applied to 40 families. At another time, the instrument was applied to 354 families in a Brazilian northeastern city. The index of agreement between the raters ranged from 0.84 for the scale items to 0.98 for the total scale, according to Kendall's coefficient. According to Cronbach's alpha, evidence of psychometric validity is adequate. Most families had a moderate degree of health, according to the scale. Therefore, the Brazilian version of the Family Health Scale showed conceptual, semantic, cultural, and operational equivalence with the original items, along with satisfactory psychometric properties for use among the Brazilian population with effectiveness and safety.


Visual feedback influences antennal positioning in flying hawk moths.
Insect antennae serve a variety of sensory functions including tactile sensing, olfaction and flight control. For all of these functions, the precise positioning of the antenna is essential to ensure the proper acquisition of sensory feedback. Although antennal movements in diverse insects may be elicited or influenced by multimodal sensory stimuli, the relative effects of these cues and their integration in the context of antennal positioning responses are not well understood. In previous studies, we have shown that fields of Böhm's bristles located at the base of the antennae provide crucial mechanosensory input for antennal positioning in flying hawk moths. Here, we present electrophysiological and behavioral evidence to show that, in addition to the Böhm's bristles, antennal muscles of hawk moths also respond to bilateral visual input. Moreover, in contrast to the mechanosensory-motor circuit, which is entirely contained within the ipsilateral side, visual feedback influences antennal positioning on both contralateral and ipsilateral sides. Electromyograms recorded from antennal muscles show that the latency of muscle responses to visual stimulation ranged from 35 to 60 ms, considerably slower than their responses to mechanosensory stimuli (<10 ms). Additionally, the visual inputs received by antennal muscles are both motion-sensitive and direction-selective. We characterized the influence of visual feedback on antennal positioning by presenting open-loop translational and rotational visual stimuli to tethered flying moths. During rotational stimuli, we observed that the antenna contralateral to the direction of the turn moved forward through larger angles than the ipsilateral antenna. These observations suggest that whereas input from the Böhm's bristles mediates rapid corrections of antennal position, visual feedback may be involved in slower, bilaterally coordinated movements of the antenna during visually guided flight maneuvers. Thus, visual feedback can modulate the set point at which the antenna is held during flight in hawk moths.


COTTON CLOSURE AS AN AERATION BARRIER IN SHAKEN FLASK FERMENTATIONS.
Oxygen transfer through a cotton plug follows Fick's law of diffusion. The apparent diffusion constant decreases as the density of cotton packing is increased. Formulas are derived which relate oxygen transfer to cotton-plug dimensions. Calculations indicate that the dimensions of a cotton plug can affect both the maximal oxygen uptake rate and the gas composition inside a shaken flask. In some situations, as with large flasks, the cotton closure can become the limiting factor to aeration.


Broadening horizons in medical management of prostate cancer.
HORMONAL THERAPY: Testosterone suppression achieved either medically or surgically is the standard initial treatment for men with advanced prostate cancer. Most men respond but the disease progresses after a median of 1-2 years. Clinical trials suggest that intermittent androgen deprivation therapy (ADT) provides equal or longer time to castration-independence than continuous ADT, and is preferred, especially since there are subtle long-term toxicities associated with ADT. Further hormonal manipulations (including addition and withdrawal of peripheral antiandrogens, steroid synthesis inhibitors such as ketoconazole, and estrogens) can be transiently effective in selected patients with castration-resistant prostate cancer (CRPC). Androgen-dependent signalling pathways remain active in most men with CRPC and are associated with mutation, changes in expression or modulation of the androgen receptor (AR); abiraterone acetate and MDV3100 are promising drugs being evaluated in clinical trials that may lead to further hormonal response. Eventually men who progress rapidly, are symptomatic, and/or develop metastasis to visceral organs require chemotherapy. Three-weekly docetaxel with prednisone has been shown to improve survival and relieve symptoms but eventually men develop progressive disease or become intolerant to docetaxel. Multiple trials are evaluating new drugs (mainly molecular targeted agents) either given first line with docetaxel chemotherapy, or to men who have progressive disease after receiving docetaxel. Cabazitaxel was shown recently to improve survival as compared to mitoxantrone when used second line and has been approved by the United States Food and Drug Administration (FDA). Despite major advances, treatment of men with advanced CRPC remains a challenge both for the seeker and giver of care.


Marker-dependent recombination in T4 bacteriophage. III. Structural prerequisites for marker discrimination.
Distance- as well as marker-dependence of genetic recombination of bacteriophage T4 was studied in crosses between rIIB mutants with known base sequences. The notion of a "basic recombination," which is the recombination within distances shorter than hybrid DNA length in the absence of mismatch repair and any marker effects, was substantiated. The basic recombination frequency per base pair can serve as an objective parameter (natural constant) of general recombination reflecting its intensity. Comparative studies of the recombination properties of rIIB mutants with various sequence changes in the mutated sites showed that the main factor determining the probability of mismatch repair in recombination heteroduplexes is the length of a continuous heterologous region. A run of A:T pairs immediately adjoining the mismatch appears to stimulate its repair. In the case of mismatches with DNA strands of unequal length, formed by frameshift mutations, the repair is asymmetric, the longer strand (bulge) being preferentially removed. A pathway for mismatch repair including sequential action of endonuclease VII (gp49)----3'----5' exonuclease (gp43)----DNA polymerase (gp43)----DNA ligase (gp30) was proposed. A possible identity of the recombinational mismatch repair mechanism to that operating to produce mutations via sequence conversion is discussed.


A clinical education and practice placements in the allied health professions: an international perspective.
This report describes the outcomes of extensive discussions surrounding clinical education and practice placement issues undertaken by an international group of allied health educators (in audiology, occupational therapy, physiotherapy, and speech pathology) who have met since 2001 as part of Universitas 21 Health Sciences annual meetings. The report outlines key issues associated with clinical education and practice placements from an international perspective and across these four allied health professions. The allied health practice context is described in terms of the range of allied health educational programs in Universitas 21 and recent changes in health and tertiary education sectors in represented countries. Some issues and benefits related to supervision during allied health students' practice placements are addressed. A new approach is proposed through partnership such that frameworks for the provision of practice placements can be created to facilitate student learning and educate and support clinical educators. A set of guidelines that can enhance partnerships and collaborative practice for the benefit of clinical education within complex and changing health/human service and educational environments is proposed.


The utility of maternal serum endocan level to predict preterm delivery within seven days in patients with threatened preterm labor.
The aim of the current study was to determine serum endocan levels in patients with threatened preterm labor and to assign whether endocan levels in patients with true preterm labor who give birth within 7 days differ from those of false preterm labor and uncomplicated pregnancy. This cross-sectional study was conducted on 58 patients diagnosed with threatened preterm labor and 31 healthy pregnant women matched for gestational age. Patients with threatened preterm labor were divided into two groups; preterm delivery (28) and term delivery (30) groups. Maternal serum endocan levels were measured with the use of an enzyme-linked immunosorbent assay kit. The median serum endocan level (pg/mL) in patients with threatened preterm labor was significantly higher than that of women with uncomplicated pregnancies (725, IQR 619-823 versus 310, IQR 218-423; p < .001 Figure 1). Subgroup analysis performed among threatened preterm labor group revealed that median serum endocan level (pg/mL) in preterm delivery group was higher compared with the other two groups (preterm 823, IQR 718-905 versus term 637, IQR 590-729 p < .001 and preterm 823, IQR 718-905 versus control 310, IQR 218-423 p < .001). The threshold value of maternal serum endocan level for predicting delivery within 7 days after admission was calculated 655 pg/mL, (the area under curve was 0.934, 95% CI 0.88-0.98, p < .001) with 85.7% sensitivity and 78.7% specificity. The mean cervical length measurement was significantly higher in the control group (p < .001); there was no significant difference in cervical length between the term and preterm delivery groups. Maternal characteristics including age, BMI, gravidity, gestational age at blood sampling, CRP and Hb levels were not significantly different between groups (p > .05). The maternal serum endocan level may be a useful marker to define high risk group for preterm delivery in patients with threatened preterm labor and similar cervical length measures.


Psychological well-being 3 years after severe stroke.
Stroke often has a very negative influence on the victims' perception of their life situation. The aim of this study was therefore to assess the subjects' long-term psychological well-being and to explore associations between subject characteristics, impairments, disabilities, and psychological well-being. Of 100 subjects rehabilitated at a specialized geriatric stroke ward after the acute phase, 47 survivors were assessed in their homes 3 years after discharge and interviewed regarding their psychological well-being with the Philadelphia Geriatric Center Morale Scale (PGCMS). Sixty-four percent of the subjects were classified as having high scores for psychological well-being or fell within the middle range. In a cluster analysis, depression was shown to have the strongest association with the subjects' PGCMS scores. Variables including the subjects' social situation and functions as well as age, gender, ability to communicate, and need for help showed a much weaker association with the PGCMS. More than half of the stroke subjects were classified as having levels of psychological well-being that were good or fairly good. The strong association between PGCMS scores and depression indicates the importance of detecting and treating depression and of following up initiated therapy after stroke.


A one-year follow-up study into the course of depression after stroke.
Stroke patients commonly suffer from neuropsychiatric disorders, such as depression, that negatively influence stroke outcome. Diagnosis, treatment and prevention of post-stroke psychiatric disorders including depression are under debate. To study the course of depression after stroke. One hundred and ninety first-ever stroke patients were screened for depressive symptoms at 1, 3, 6, 9, and 12 months after stroke. Diagnosis of depression was made according to the DSM-IV criteria of major and minor depression. Follow-up was completed in 138 patients. The cumulative incidence of post-stroke depression (PSD) in 1 year was 36.2%. One month after stroke the prevalence of PSD was 18.8%. Thirty percent of patients who were depressed in the first three months did not reach cut-off levels on depression screening instruments at the following assessments. In 44% of these patients symptoms recurred. Recurrent cases were older than patients with limited disease. In 40% of PSD patients depression persisted for at least two consecutive following follow-up visits. Persistent cases were more disabled and suffered more often from major depression. Half of PSD patients become depressed within the first month after stroke. Although most patients recover, a clinician has to be aware that symptoms can recur especially in older patients and that in patients with major depression symptoms may be persistent. In these patients treatment should be considered, whereas in patients with limited disease an observational approach may suffice.


Diversity of Atopic Dermatitis and Selection of Immune Targets.
Atopic dermatitis (AD) is a heterogeneous immune-mediated skin disorder affecting people of all ages and ethnicities. Despite the development of targeted therapeutics such as biologics and JAK inhibitors, attaining complete clinical efficacy remains difficult. This therapeutic challenge may be attributed to the complex pathogenesis of AD. While the Th2 axis has been extensively studied, recent advancements have started to reveal the involvement of additional immune pathways including Th1, Th17, and Th22. Understanding the interplay of these immune axes may contribute to a more personalized therapeutic approach based on patients' molecular profile, with the prospect of improving clinical outcome. This review will discuss studies exploring the molecular profile of AD in both skin and blood across age, ethnicity/race, disease chronicity, IgE levels, filaggrin mutation status, and AD association with other atopic conditions. Moreover, it will explore the potential of personalized treatment strategies based on a patient's distinct immune signature.


Clinical Features and Neurologic Complications of Children Hospitalized With Chikungunya Virus in Honduras.
The first case of Chikungunya virus in Honduras was identified in 2014. The virus has spread widely across Honduras via the Aedes aegypti mosquito, leading to an outbreak of Chikungunya virus (CHIKV) in 2015 that significantly impacted children. A retrospective chart review of 235 children diagnosed with CHIKV and admitted to the National Autonomous University of Honduras Hospital Escuela (Hospital Escuela) in Tegucigalpa, Honduras, was accomplished with patients who were assessed for clinical features and neurologic complications. Of 235 children admitted to Hospital Escuela with CHIKV, the majority had symptoms of fever, generalized erythematous rash, and irritability. Fourteen percent had clinical arthritis. Ten percent of patients had seizures. Six percent had meningoencephalitis. There were 2 childhood deaths during the course of this study, one from meningoencephalitis and another from myocarditis. Chikungunya virus can cause severe complications in children, the majority of which impact the central nervous system.


Relationships between arterial hypertension and renal allograft survival in African-American patients.
In previous studies, we showed that in African-American patients arterial hypertension during the first 6 months after transplantation is associated with a high risk of renal allograft loss. In this study, we sought to examine the relationships between pretransplant blood pressure (preBP), blood pressure early after transplantation (postBP), and allograft function and survival. The study included 116 African-American recipients of first cadaveric renal allografts followed for 64 +/- 40 months. Prior to transplantation, 78% of the patients required antihypertensive medications and 59% had poorly controlled BP (average mean arterial pressure, > or =107 mm Hg). Blood pressure levels increased significantly during the first month posttransplant, particularly in patients with poorly controlled preBP. During the first 6 months posttransplant, 95% of patients required antihypertensive drugs; after the transplant, patients required significantly more and higher doses of antihypertensives compared with pretransplant. In 38% of the patients, postBP remained high despite therapy. The level of postBP correlated with the patient's weight pretransplant and with the level of preBP. Pretransplant BP correlated with postBP 1 month after transplantation (r = 0.4, P < 0.0001), and 70% of the patients with poorly controlled postBP had uncontrolled preBP. Patients with poorly controlled preBP had worse graft survival than patients with well-controlled preBP (P = 0.03 by Cox regression). Furthermore, compared with patients with well-controlled postBP, patients with high postBP had higher serum creatinine at 10 days (P = 0.04) and at 6 months (P = 0.0004) posttransplant; these patients had reduced graft survival (P = 0.0006 by Cox). We found no objective evidence of differences in patient compliance between individuals with high postBP and those with well-controlled postBP. This study confirms the association between high postBP and reduced renal allograft survival in African-American patients. In addition, these results show that the level of preBP can be used to identify patients at high risk of developing severe hypertension immediately after transplantation and those at risk for renal allograft failure.


Signs and symptoms of mercury-exposed gold miners.
Gold miners use mercury to extract gold from ore adding liquid mercury to the milled gold-containing ore. This results in a mercury-gold compound, called amalgam. Miners smelt this amalgam to obtain gold, vaporizing it and finally inhaling the toxic mercury fumes. The objective was to merge and analyze data from different projects, to identify typical signs and symptoms of chronic inorganic mercury exposure. Miners and community members from various artisanal small-scale gold mining areas had been examined (Philippines, Mongolia, Tanzania, Zimbabwe, Indonesia). Data of several health assessments were pooled. Urine, blood and hair samples were analyzed for mercury (N = 1252). Questionnaires, standardized medical examinations and neuropsychological tests were used. Participants were grouped into: Controls (N = 209), living in an exposed area (N = 408), working with mercury as panners (N = 181), working with mercury as amalgam burners (N = 454). Chi2 test, linear trend test, Mann-Whitney test, Kruskal-Wallis test, correlation coefficient, Spearman's rho, and analysis of variance tests were used. An algorithm was used to define participants with chronic mercury intoxication. Mean mercury concentrations in all exposed subgroups were elevated and above threshold limits, with amalgam burners showing highest levels. Typical symptoms of chronic metallic mercury intoxication were tremor, ataxia, coordination problems, excessive salivation and metallic taste. Participants from the exposed groups showed poorer results in different neuropsychological tests in comparison to the control group. Fifty-four percent of the high-exposed group (amalgam burners) were diagnosed as being mercury-intoxicated, compared to 0% within the control group (Chi2 p < 0.001). Chronic mercury intoxication, with tremor, ataxia and other neurological symptoms together with a raised body burden of mercury was clinically diagnosed in exposed people in artisanal small-scale mining areas. The mercury exposure needs to be urgently reduced. Health care systems need to be prepared for this emerging problem of chronic mercury intoxication among exposed people. Int J Occup Med Environ Health 2017;30(2):249-269.


The nature of haem a3 in the oxidized state of cytochrome c oxidase. Evidence from low-temperature magnetic-circular-dichroism spectroscopy in the near infrared region.
The magnetic-circular-dichroism (m.c.d.) spectra of oxidized 'resting' bovine cytochrome c oxidase and the cyanide-inhibited form are reported at 5.15 T and at 4.2 K along with m.c.d. magnetization curves plotted at selected wavelengths. In both spectra there are features at 790nm and 1564nm due to Cua and haem a respectively, the e.p.r.-detectable components of the enzyme. There is a new peak at 1946nm only in the spectrum of the cyanide-inhibited enzyme. Arguments are advanced that assign this to low-spin ferric haem a3 bridged to Cua3, thereby forming a ferromagnetically coupled pair of metal ions.


MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification.
MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. MAGIC-web is accessible from http://ms.iis.sinica.edu.tw/MAGIC-web/index.html.