Endothelial Cells in Antibody-Mediated Rejection of Kidney Transplantation: Pathogenesis Mechanisms and Therapeutic Implications.
Antibody-mediated rejection (AMR) has been identified as a main obstacle for stable immune tolerance and long survival of kidney allografts. In spite of new insights into the underlying mechanisms of AMR, accurate diagnosis and efficient treatment are still challenges in clinical practice. Endothelium is the first barrier between recipients' immune systems and grafts in vascularized organ transplants. Considering that endothelial cells express a number of antigens that can be attacked by various allo- and autoantibodies, endothelial cells act as main targets for the recipients' humoral immune responses. Importantly, emerging evidence has shown that endothelial cells in transplants could also initiate protective mechanisms in response to immune injuries. A better understanding of the role of endothelial cells during the pathogenesis of AMR might provide novel therapeutic targets. In the present review, we summarize the antigens expressed by endothelial cells and also discuss the activation and accommodation of endothelial cells as well as their clinical implications. Collectively, the progress discussed in this review indicates endothelial cells as promising targets to improve current diagnosis and therapeutic regimens for AMR.


[Compulsory collegial guidance. What do candidates in general practice think about training of practical procedures?].
In 1994 a new module addressing the quality of practical procedures was added to the Norwegian general practice specialisation programme. Over a five-year period 31 practical procedures must be performed under the supervision of fellow GPs. In 1995 a survey was carried out by questionnaire among all specialist candidates registered in the new programme (n = 165, response rate 83%) and a control group consisting of all candidates registered in 1993 (n = 162, response rate 62%). The aims of the survey were to evaluate the candidates' motivation, self-rated level of competence, and the presence of barriers to programme implementation. The main group and control group were almost identical; mean age has 36.5 years, 37% were females. There were no differences in the self-rated levels of competence between the groups. The majority (80%) reported a need to improve their performance of practical procedures, and 93% stated that mutual guidance with colleagues would be of considerable benefit by improving technical performance, professional confidence and the quality of relationships with colleagues. The main barriers to mutual guidance were shortage of time, lack of structured opportunities for performing procedures in the presence of colleagues, and lack of instruction manuals or videos detailing the correct performance of procedures.


Intussusception of the appendix.
Two cases of intussusception of the appendix are reported--one caused by adenocarcinoma and adenomatous polyp and the other by an endometrioma. Appendiceal intussusception and adenocarcinoma are both uncommon entities and this is the first report of the two occurring concomitantly. Due to variable symptoms, the correct diagnosis of appendiceal intussusception has rarely been made preoperatively. Classification, symptoms, radiographic appearance, and differential diagnosis are discussed, and the authors suggest a new classification for intussusception of the appendix.


Glutamine synthetase isozymes in germinating barley seeds.
Glutamine synthetase (GS; EC 188.8.131.52) is a key enzyme of ammonia assimilation in higher plants. In the present study the subunit composition and localization of GS in germinating barley (Hordeum vulgare) seed have been clarified. Analysis of the GS polypeptide composition by immunoblotting revealed two different polypeptides. A and B, with a molecular mass of 42 and 40 kDa, respectively. In the scutellum subunit A was already present in the ungerminated seed and remained unchanged, whereas subunit B appeared on day 2 and increased about 5-fold during germination. Polypeptide B also appeared later during germination in the aleurone layer, roots and weakly in the etiolated shoots. By immunogold microscopy, GS was detected in the scutellum and the aleurone layer of barley seeds during germination. Subcellular localization of GS on ultrathin cryosections showed that a cytosolic isozyme was present in the scutellum. Our study confirms that only a cytosolic GS is expressed in barley seed, and its subunit composition changes during germination.


Bridging the common factors and empirically supported treatment camps: comment on Laska, Gurman, and Wampold.
We comment on Laska, Gurman, and Wampold's (2014, pp. 467-481) article, "Expanding the Lens of Evidence-Based Practice in Psychotherapy: A Common Factors Perspective." Our reactions to this scholarly review of the 2 foremost approaches to evidence-based psychotherapy (i.e., the common factors [CF] and the empirically supported treatment [EST] perspectives) include substantial agreement on many points, some attempts to reframe the ostensible gap between the perspectives, and our own attempt to conceptually and empirically bridge the perspectives in the form of a model that we call context-responsive psychotherapy integration. We also offer potential future research directions that can help elevate the scientific credibility of the CF model and allow CF and EST researchers to unite in uncovering clinical change mechanisms.


[Progress on molecular biology of Pneumocystis--for hundred years since its discovery].
2009 marks the 100th anniversary of the first description of Pneumocystis, an organism that was initially classified as a protozoan and later in 1988, was phylogenetically reclassified in the fungal kingdom. The organism was ignored for its first 50 years but that has subsequently been recognized as an important pathogen in immunocompromised patients, especially patients with acquired immune deficiency syndrome(AIDS). This paper reviewed recent progress on the molecular biology, involving in the life cycle and metabolism of the organism.


[Bart syndrome associated to lethal junctional epidermolysis bullosa (Herlitz form)].
We present the case of a newborn with congenital absence of skin in the anterior part of the left leg that shortly after developed bulla and erosions in hands, feet, ears, buttocks and mouth. The cutaneous biopsy and ultrastructural and immunohistochemical studies showed a subepidermal bulla in the lamina lucida, absence of hemidesmosomes and marked decrease of laminin 5, thus establishing the diagnosis of Bart syndrome associated to the Herlitz form of lethal junctional epidermolysis bullosa. Bart syndrome consists of congenital and localized absence of skin, nail abnormalities and mucoc-cutaneous bullae. It is usually associated to dystrophic epidermolysis bullosa. The Herlitz form of junctional epidermolysis bullosa is a rare variant, usually lethal that is produced by mutations in the genes coding for the anchor protein laminin 5. To our knowledge this is the second case that reports an association between Bart syndrome and lethal junctional epidermolysis bullosa and the first in which the results of immunofluorescence mapping are published.


Linezolid pharmacokinetics in pediatric patients: an overview.
There are a number of physiologic and developmental differences between children and adults that can influence the absorption, distribution, metabolism and elimination of a drug. Therefore it is important to determine the specific pharmacokinetic characteristics for individual drugs in pediatric patients so that appropriate age-specific dosage regimens can be developed and evaluated in clinical trials. This review summarizes the pharmacokinetic parameters of linezolid in pediatric patients and the rationale for the approved dosing recommendations for this population. The pharmacokinetics of linezolid in pediatric patients has been evaluated in 4 clinical trials, including >180 patients ranging in age from preterm newborn infants up to 18 years of age. In all of these studies, patients received a single intravenous dose of linezolid. Plasma linezolid concentrations have been determined by validated high performance liquid chromatography (adult studies) or liquid chromatography/mass spectrometry/mass spectrometry (pediatric studies) methods. The pharmacokinetics of linezolid, especially elimination clearance, is age-dependent. Children younger than 12 years of age have a smaller area under the drug concentration-time curve, a faster clearance and a shorter elimination half-life than adults. Although clearance rates in newborn infants are similar to those in adults, clearance increases rapidly during the first week of life, becoming 2- to 3-fold higher than in adults by the seventh day of life. The clearance of linezolid decreases gradually among young children, becoming similar to adult values by adolescence. The pharmacokinetics of linezolid in children age 12 years and older is not significantly different from that of adults. Because of the higher clearance and lower area under the drug concentration-time curve, a shorter dosing interval for linezolid is required for children younger than 12 years of age to produce adequate drug exposure against target Gram-positive pathogens.


Nanometer-size cluster formation in alkali-metal-doped fullerene layers.
Kinetic Monte Carlo methods have been used to simulate structural transformations in fullerene layers during electrochemical intercalation with alkali-metal ions (A). Special attention is paid to the thermodynamic stability of the A(x)C(60) phases. The calculations point out a phase separation in the doped fullerene layer into alkali-metal-rich and alkali-metal-depleted areas at room temperature. The final state is represented by two phases which coexist as a stable fine mixture of nanoscale particles. The instability of homogeneous layers has potentially critical impact on their electrical properties and can explain the formation of nanostructures (20-50 nm) at the fullerene-electrolyte interface. Rb(3)C(60) clusters are predicted to be larger than K(3)C(60) ones for equal mean alkali-metal concentrations. Experimental data on electrochemical metal deposition on alkali-metal-doped fullerene substrates-in particular, atomic force microscopy measurements-are also consistent with the model proposed.


The fundamental role of the endocannabinoid system in endometrium and placenta: implications in pathophysiological aspects of uterine and pregnancy disorders.
The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and their metabolic enzymes N-acylphosphatidylethanolamine-specific phospholipase D, fatty acid amide hydrolase, diacylglycerol lipase and monoacylglycerol lipase. This system is involved in the modulation of essential physiological processes. Its role in the reproductive system has become significantly important in recent years, given its major role in events such as gametogenesis, decidualisation, implantation and placentation. In this paper, we review the literature and summarize the role of the ECS elements in reproduction and their potential as early markers for diagnosis of reproductive disorders or as pharmacological targets for treatment. Original research and review papers published from 1964 to June 2019 were selected in terms of relevance, reliability and quality by searching PubMed, MEDLINE and Web of Science, using the following search terms: endocannabinoid system and endometriosis; endocannabinoid system and ectopic pregnancy; endocannabinoid system and miscarriage; endocannabinoid system and pre-eclampsia; endocannabinoid system and endometrial cancer; endocannabinoid system and reproduction; endocannabinoid, endometrium; placenta; N-acylethanolamines; anandamide; 2-arachidonoylglycerol; and cannabinoids. This review demonstrates relevant information concerning ECS alterations in endometriosis, ectopic pregnancy, miscarriage, pre-eclampsia and endometrial cancer. We highlight the importance of the endocannabinoids in endometrial and placental physiology and pathophysiology, from studies in vitro and in vivo and in clinical observations. The most studied of the endogenous cannabinoids is AEA. The levels of AEA were increased in plasma of patients with endometriosis and miscarriage, as well as in the fallopian tube of women with ectopic pregnancy and in endometrial biopsies of endometrial cancer. Changes in the pattern of expression of the cannabinoid receptor CB1 were also observed in endometrial biopsies of endometriosis, fallopian tube and decidua of patients with ectopic pregnancy and pre-eclamptic placenta. Moreover, alterations in CB2 expression have been reported in association with endometrial cancer. In general, studies on the cannabinoid signalling through CB2 and on the biological activities of the other major endocannabinoid, namely 2-AG, as well as its metabolic enzymes are scarce and avidly required. The pathophysiological mechanisms involved in the described endometrial and placental pathologies are still unclear and lack the means for an early diagnosis. Based on current evidence, though alterations in ECS are demonstrated at tissue level, it is difficult to associate plasmatic changes in AEA with specific endometrial and placental diseases. Thus, pairing alterations in AEA levels with 2-AG and/or other endocannabinoid-like molecules may provide more accurate and early diagnoses. In addition, patients may benefit from new therapies that target the ECS and endocannabinoid signalling.


[A Case of Advanced Breast Cancer with Liver Metastasis Successfully Treated with Multi-Disciplinary].
We report a case of advanced breast cancer with liver metastasis(T2N1M1, Stage IV )achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was 37-year-old woman who had breast lump and axillary lymph nodes swelling with liver metastasis. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma, negative for estrogen receptor and progesterone receptor, and positive for HER2/neu protein expression. The Ki-67 positive cell index was 40%. She received 16 courses of DOC plus HER plus PER(docetaxel 75mg/m / 2, trastuzumab 6 mg/kg, pertu- zumab 450mg/body, and received 4 courses of EC(epirubicin 90mg/m / 2, cyclophosphamide 600 mg/m2). The breast lesion and liver metastatic lesion disappeared after chemotherapy. We checked up whole body. There was no metastatic lesion. Therefore, we diagnosed a clinical complete response. We performed muscle preserving mastectomy and axillary lymph nodes dissection. The pathological diagnosis from resected specimens were pathological complete response. The surgical margin was negative. She was started the endocrine therapy by tamoxifen(20mg/day). Three years after surgery, she was well without metastases. Multi-disciplinary therapy can improve patient QOL and the clinical outcomes in Stage IV advanced breast cancer.


Contacts with a Canadian "street-level" Drug and Crisis Centre, 1975-1978.
This paper presents the work and functioning of the distress Centre/Drug Centre, an agency in Calgary, Alberta, Canada, which has evolved from a youth-oriented drug centre to a general crisis centre. It is staffed by volunteers who are supported by professional staff, and offers a 24-hour telephone service throughout the week. The paper reviews the continuing evolution of this service, the drugs most frequently noted in contacts involving crisis and suicide attempts, and the role of crisis centres that use volunteers as front-line workers. The years 1975-1978 were a period in which alcohol was the drug most frequently reported to be associated with crisis and attempted suicide.


Analysis of aberrant pre-messenger RNA splicing resulting from mutations in ATP8B1 and efficient in vitro rescue by adapted U1 small nuclear RNA.
ATP8B1 deficiency is a severe autosomal recessive liver disease resulting from mutations in the ATP8B1 gene characterized by a continuous phenotypical spectrum from intermittent (benign recurrent intrahepatic cholestasis; BRIC) to progressive familial intrahepatic cholestasis (PFIC). Current therapeutic options are insufficient, and elucidating the molecular consequences of mutations could lead to personalized mutation-specific therapies. We investigated the effect on pre-messenger RNA splicing of 14 ATP8B1 mutations at exon-intron boundaries using an in vitro minigene system. Eleven mutations, mostly associated with a PFIC phenotype, resulted in aberrant splicing and a complete absence of correctly spliced product. In contrast, three mutations led to partially correct splicing and were associated with a BRIC phenotype. These findings indicate an inverse correlation between the level of correctly spliced product and disease severity. Expression of modified U1 small nuclear RNAs (snRNA) complementary to the splice donor sites strongly improved or completely rescued splicing for several ATP8B1 mutations located at donor, as well as acceptor, splice sites. In one case, we also evaluated exon-specific U1 snRNAs that, by targeting nonconserved intronic sequences, might reduce possible off-target events. Although very effective in correcting exon skipping, they also induced retention of the short downstream intron. We systematically characterized the molecular consequences of 14 ATP8B1 mutations at exon-intron boundaries associated with ATP8B1 deficiency and found that the majority resulted in total exon skipping. The amount of correctly spliced product inversely correlated with disease severity. Compensatory modified U1 snRNAs, complementary to mutated donor splice sites, were able to improve exon definition very efficiently and could be a novel therapeutic strategy in ATP8B1 deficiency as well as other genetic diseases.


LMD method and multi-class RWSVM of fault diagnosis for rotating machinery using condition monitoring information.
Timely and accurate condition monitoring and fault diagnosis of rotating machinery are very important to maintain a high degree of availability, reliability and operational safety. This paper presents a novel intelligent method based on local mean decomposition (LMD) and multi-class reproducing wavelet support vector machines (RWSVM), which is applied to diagnose rotating machinery faults. First, the sensor-based vibration signals measured from the rotating machinery are preprocessed by the LMD method and product functions (PFs) are produced. Second, statistic features are extracted to acquire more fault characteristic information from the sensitive PF. Finally, these features are fed into a multi-class RWSVM to identify the rotating machinery health conditions. The experimental results validate the effectiveness of the proposed RWSVM method in identifying rotating machinery fault patterns accurately and effectively and its superiority over that based on the general SVM.


Ophthalmological side effects of interferon therapy of chronic hepatitis C.
Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity. We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment. IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy. Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately it's asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important.


A novel family of short interspersed repetitive elements (SINEs) from cichlids: the patterns of insertion of SINEs at orthologous loci support the proposed monophyly of four major groups of cichlid fishes in Lake Tanganyika.
Short interspersed repetitive elements (SINEs) have been shown to be excellent markers of molecular phylogeny, since the integration of a SINE at a particular position in a genome can be considered an unambiguous derived homologous character. In the present study, we isolated a new family of SINEs from cichlids in Lake Tanganyika, whose speciation and diversification have been regarded as prime examples of explosive adaptive radiation. Members of this new SINE family, which we named the AFC family, are about 320 bp in length, and each has a tRNA-related region in its 5' region, as do most of the members of SINE families reported to date. A dot blot hybridization experiment showed that this family is distributed extensively in the genomes of cichlids in Africa, with estimated copy numbers of 2 x 10(3)-2 x 10(4) per haploid genome. Our investigations of the patterns of insertion of members of this family at six orthologous loci demonstrated clearly that four previously identified tribes, namely, the Lamprologini, Ectodini, Tropheini, and Perissodini, each form a monophyletic group. These results provide a basis for the elucidation of the phylogenetic framework of the cichlid fishes in Lake Tanganyika.


The relationship between neuropsychological functioning and psychopathology in temporal lobe epileptic patients.
With the use of Goldberg's method of Minnesota Multiphasic Personality Inventory (MMPI) analysis, evidence has been recently provided of a positive relationship between psychopathology and deficits in neuropsychological functioning in epileptic patients. The present study attempted to replicate this finding using more precise and appropriate criteria for grouping patients according to severity of neuropsychological impairment. Application of Goldberg's MMPI Rules to 34 temporal lobe epileptic patients grouped according to their neuropsychological status (nonimpaired or impaired) failed to support these findings. Possible reasons for the discrepant results, including differing methodologies and seizure patient characteristics across studies, are discussed.


[Epididymitis after prostatic adenomectomy--24-years observations].
Authors have retrospectively reviewed records of 6811 patients with BPH treated during the last 24 years who underwent suprapubic and transurethral adenomectomy to evaluate the incidence of postoperative epididymitis. Only in 44 cases was diagnosed acute postoperative epididymitis (0.64%). Most commonly the postoperative epididymitis was noted following transvesical adenomectomies (1.53%), less commonly following retropubic (Millin's) surgery (1.09%), and most rarely following transurethral resection of the prostate (TURP) (0.11%). It was observed that the postoperative epididymitis was closely associated with urinary tract infections (UTI). The most common pathogen isolated in the postoperative epididymitis were Gram negative bacteria. No difference was noted between two groups (our patients without prophylactic vasectomy compared with the data from literature with prophylactic vasectomy) in the incidence of postoperative epididymitis. Incidence of postoperative epididymitis decreased significantly in the last two decades. Surgical techniques that allow for a shorter postoperative catheterization resulted in less frequent urinary tract infection which in turn led to decrease in the postoperative epididymitis. A course of suitable antibiotic therapy often permits to cure postoperative epididymitis without a need for surgery (70.45%). Vasectomy as the routine prophylactic intervention prior to prostatic surgery is no longer indicated.


Envelope Stress Responses.
The gram-negative bacterial envelope is a complex extracytoplasmic compartment responsible for numerous cellular processes. Among its most important functions is its service as the protective layer separating the cytoplasmic space from the ever-changing external environment. To adapt to the diverse conditions encountered both in the environment and within the mammalian host, Escherichia coli and Salmonella species have evolved six independent envelope stress response systems . This review reviews the sE response, the CpxAR and BaeSR two-component systems (TCS) , the phage shock protein response, and the Rcs phosphorelay system. These five signal transduction pathways represent the most studied of the six known stress responses. The signal for adhesion to abiotic surfaces enters the pathway through the novel outer membrane lipoprotein NlpE, and activation on entry into the exponential phase of growth occurs independently of CpxA . Adhesion could disrupt NlpE causing unfolding of its unstable N-terminal domain, leading to activation of the Cpx response. The most recent class of genes added to the Cpx regulon includes those involved in copper homeostasis. Two separate microarray experiments revealed that exposure of E. coli cells to high levels of external copper leads to upregulation of several Cpx regulon members. The BaeSR TCS has also been shown to mediate drug resistance in Salmonella. Similar to E. coli, the Bae pathway of Salmonella enterica mediates resistance to oxacillin, novobiocin, deoxycholate, β-lactams, and indole.


Fat-globule size in a propofol emulsion containing sodium metabisulfite.
The size distribution of fat globules from previously unopened, unexpired vials of Gensia Sicor's 1% propofol injectable lipid emulsion was studied. Fat globules in 20-mL samples from 50- and 100-mL vials of Gensia Sicor's 1% propofol emulsion containing 0.025% sodium metabisulfite were measured and counted by a laser-based, single-particle optical sensing technique. Measurements were performed during May 2001, June 2002, and October 2002, corresponding, respectively, to 17-21, 5-9, and 1-5 months before the vials' expiration dates, depending on the lot. Between measurements, the vials were stored at 4-22 degrees C. It was assumed that the pH for all lots was 4.5-6.4. Two separate lots of the innovator propofol emulsion (AstraZeneca) containing EDTA and having a labeled pH of 7.0-8.5 were analyzed in October 2002 in a post hoc assessment as the vials neared their expiration date. In May 2001, the volume-weighted percentage of fat globules with a diameter of >5 microm (PFAT5) was <0.05% for all seven Gensia Sicor lots. In four of the lots, PFAT5 increased significantly between May 2001 and June 2002. In all seven lots, PFAT5 increased significantly between May 2001 and October 2002. The two lots of the AstraZeneca product, tested two or three months before expiration, had low PFAT5 values. In samples from unopened, unexpired, and properly stored vials of Gensia Sicor propofol formulated at pH 4.5-6.4, PFAT5 increased over 18 months and in most cases exceeded 0.05% by the end of the study.


Inhibition of posterior capsule opacification: the effect of colchicine in a sustained drug delivery system.
We investigated the effect of colchicine in a sustained drug delivery system on posterior capsule opacification (PCO) in rabbit eyes. A polymer matrix wafer, which diffused colchicine at a steady rate, was implanted in the capsular bag of 34 eyes after the lens material was removed by endocapsular phacoemulsification. Three different drug concentrations were used in the rabbit eyes, which were compared with control eyes containing the polymer matrix wafer without colchicine. The mean PCO score was highest in the control group without colchicine and increased steadily over 12 weeks. The rate of PCO formation in all eyes treated with colchicine was significantly lower than in the control group. There was no statistically significant improvement in PCO inhibition with the higher colchicine dosages. Side effects included inflammatory anterior chamber reaction and corneal and retinal complications and were most notable with the highest drug concentration. Slow release of colchicine reduces PCO formation in the rabbit. The optimal biocompatible dosage must be carefully determined and warrants further investigation.


Comparative physical genome mapping of malaria vectors Anopheles sinensis and Anopheles gambiae.
Anopheles sinensis is a dominant natural vector of Plasmodium vivax in China, Taiwan, Japan, and Korea. Recent genome sequencing of An. sinensis provides important insights into the genomic basis of vectorial capacity. However, the lack of a physical genome map with chromosome assignment and orientation of sequencing scaffolds hinders comparative analyses with other genomes to infer evolutionary changes relevant to the vector capacity. Here, a physical genome map for An. sinensis was constructed by assigning 52 scaffolds onto the chromosomes using fluorescence in situ hybridization (FISH). This chromosome-based genome assembly composes approximately 36% of the total An. sinensis genome. Comparisons of 3955 orthologous genes between An. sinensis and Anopheles gambiae identified 361 conserved synteny blocks and 267 inversions fixed between these two lineages. The rate of gene order reshuffling on the X chromosome is approximately 3.2 times higher than that on the autosomes. The physical map will facilitate detailed genomic analysis of An. sinensis and contribute to understanding of the patterns and mechanisms of large-scale genome rearrangements in anopheline mosquitoes.


Training Community Health Workers to Address Disparities in Dementia Care: A Case Study From Oklahoma With National Implications.
The projected increase of dementia in the diverse aging US population calls for a well-prepared public health workforce. Community health workers (CHWs) can address dementia in culturally appropriate ways. Collaborating with stakeholders, we developed a train-the-trainer curriculum for CHWs and used a virtual training platform to test its feasibility with 77 CHWs. Pre-/post-evaluation data demonstrated modestly increased dementia knowledge scores. Training participants valued the resources shared and interacting with peers. Disseminating this training could contribute to closing gaps in dementia care in diverse communities, along with policies supporting CHWs as a workforce that reduces age-related disparities and promotes health equity.


Longer survival of a patient with glioblastoma resected with 5-aminolevulinic acid (5-ALA)-guided surgery and foreign body reaction to polyglycolic acid (PGA) suture.
In recent years, there is a growing evidence that using 5-aminolevulinic acid (5-ALA)-guided resection of a cerebral glioblastoma, associated with chemoradiotherapy determine a prolonged survival of these patients, even though this period do not exceed 15 months. 5-ALA is a natural biochemical precursor of heme that is metabolized to fluorescent porphyrins, particularly protoporphyrin IX (PPIX) and no foreign reaction were noted until now. However, foreign body reaction developing in neurosurgery is documented in a few number of cases to suture material, surgical hemostatic material, or surgical glove starch, but up to now we could not find any article about granulomatous inflammation to polyglycolic acid (PGA) suture after brain tumor resection. Here we present a case of a delayed foreign body granuloma to PGA suture diagnosed after 10 months following fluorescence-guided surgery with 5-ALA for resection of a cerebral glioblastoma that was difficult to diagnosis both clinically and on magnetic resonance imaging (MRI). Moreover, the survival time was longer. We correlate the appearance of foreign body granuloma with the patient's persistent pre- and postoperative lymphocytosis. We also suggest that the chronic inflammation inhibited the proliferation of any tumoral cells which could remain in the tumor bed because we did not noticed on serial MRI scans a rapidly tumor growth during the first 10 months after the initial surgery as we have expected to be for a glioblastoma.


Diagnosis of acute myocardial ischaemia using probabilistic methods.
The present study was undertaken to test the effectiveness of an established equation for estimating the probability of acute cardiac ischaemia, but in an environment different from that in which it was developed. A total of 255 patients who presented to the accident and emergency department of Glasgow Royal Infirmary with symptoms suggesting acute ischaemic heart disease were enrolled in the study. Their clinical data and ECG measurements were used as input to the Time-Insensitive Predictive Instrument (TIPI) equation to calculate the probability of acute myocardial ischaemia being present. Receiver operating characteristic (ROC) curves were derived to evaluate the usefulness of the equation in diagnosing acute myocardial infarction versus nonmyocardial infarction and acute cardiac ischaemia verses nonischaemic chest pain. For the diagnosis of acute cardiac ischaemia versus noncardiac chest pain, the area under the ROC curve was 0.61 (95% CI 0.55-0.67). For the diagnosis of acute myocardial infarction versus nonmyocardial infarction, there was increased performance with the area under the ROC curve being 0.71 (95% CI 0.65-0.76). This compares with the originally published findings of a value of 0.88 for the area under the curve for the diagnosis of acute myocardial ischaemia versus noncardiac chest pain. The study suggests that equations for the diagnosis of acute cardiac ischaemia developed in one centre may not readily translate elsewhere, possibly due to varying interpretations of the clinical and ECG criteria used.


Complication Rates and Outcomes After Hysterectomy in Transgender Men.
To describe the rate and 30-day outcomes after gender affirmation surgery in transgender men. We conducted a cross-sectional population-based study. Patients with male gender who underwent hysterectomy for benign indications between 2013 and 2016 in the American College of Surgeons' National Surgical Quality Improvement database were identified. Propensity score matching was performed to ameliorate selection bias. Student t test and Mann-Whitney tests were used to compare continuous variables between two groups where appropriate. The χ and Fisher exact tests were used where appropriate to compare categorical variables across groups. Logistic regression models were used to evaluate factors associated with any postoperative adverse event. Of 159,736 hysterectomies performed during the study period, 521 (0.3%) were performed in transgender men. The mean age was 23.9±13.8 years, and the median body mass index was 29.0 (range 24.8-34.2). The majority of patients were white (64.5%). The most common specified diagnosis associated with hysterectomy was gender identity disorder (20.9%). Laparoscopy was the most common route (57.2%) followed by laparoscopic-assisted vaginal hysterectomy (20.0%) and abdominal hysterectomy (15.2%). After propensity matching was performed, the composite rate of postoperative complications was similar between the transgender male and control groups (3.4% vs 3.3%, P=.92). On multivariate logistic regression controlling for age, presence of a major medical comorbidity, and primary mode of surgery, transgender male status and presence of a major medical comorbidity were not significantly associated with complications (adjusted odds ratio [OR] 1.11, 95% CI 0.56-2.10 and adjusted OR 1.16, 95% CI 0.58-2.27, respectively). Age remained weakly associated with postoperative complications (adjusted OR 1.04, 95% CI 1.01-1.06), whereas minimally invasive approaches to hysterectomy were significantly associated with lower incidences of complications (vaginal, adjusted OR 0.04, 95% CI 0.002-0.17; laparoscopic adjusted OR 0.09, 95% CI 0.04-0.18; and laparoscopic-assisted vaginal hysterectomy, adjusted OR 0.07, 95% CI 0.02-0.20). Less than 1% of hysterectomies performed annually are for transgender male patients. Postoperative complications after hysterectomy in this patient population are similar to the complication rates found in cisgender women.


Importance of oviduct relaxation in artificial insemination of turkeys.
This experiment was designed to determine whether or not relaxation of the turkey oviduct prior to the release of the semen was necessary for optimal fertilization to occur with artificial insemination. A total of 96 large type turkey caged laying hens were inseminated with 0.025 ml. of pooled semen near the area of the uterovaginal junction while the oviduct was still everted or after pressure on the hen was released and the oviduct returned to its non-everted position with the insemination tube in place. The difference in fertility of 9% between the non-everted (87.4%) and everted (78.5%) group was significant (P less than 0.01). The embryonic mortality of the non-everted group (10.6%) was significantly lower (P less than 0.01) than in the everted group (13.2%).


MicroRNA-146a targets PRKCE to modulate papillary thyroid tumor development.
MicroRNAs are single-stranded noncoding RNAs composed of approximately 22 nucleotides that suppress gene expression by selectively binding via base-pairing to the complementary 3'-untranslated region (3'-UTR) of messenger RNA transcripts. Protein kinase C epsilon (PKCε) is an important modulating member of the transducing Ras/Raf-1 signal pathway; a computational search revealed miR-146a putatively binds to the 3'-UTR of the PRKCE gene, and thus decreasing PKCε expression. Moreover, PKCε inhibits mitochondrial apoptosis and is associated with the Bcl family. However, it has been previously reported that miR-146a expression in papillary thyroid carcinoma (PTC) is slightly elevated. Thus, we hypothesized that because miR-146a expression depends on nuclear factor kappaB (NF-κB) activation and NF-κB expression is elevated in PTC, miR-146a is potentially upregulated in PTC via negative feedback of NF-κB, and thus suppressing PKCε expression. In our study, we investigated whether overexpression of miR-146a, a tumor-suppressing-miR, in PTC cells decreases cell survival and induces apoptosis. Luciferase reporter assay analysis confirmed the direct binding of miR-146a and PRKCE 3'-UTR. Specific overexpression of exogenous miR-146a significantly decreased PKCε levels in PTC cell line NPA-187 and increased apoptosis. Additionally, using stably expressing miR-146a thyroid carcinoma cells to establish subcutaneous tumors, the tumor growth exhibited significant inhibition. Our study confirmed the tumor-suppressing role of miR-146a in thyroid carcinoma cells and contributes to the knowledge regarding modulation of Ras/Raf-1 signal transduction and apoptosis via PKCε targeted by miR-146a in PTC; moreover, our findings confirmed that miR-146a is involved in the feedback system of the classical NF-κB signal pathway in PTC.


Transvascular removal of catheter fragments from the great vessels and heart.
Embolization of catheter fragments or fractured spring guidewires used during cardiac catheterization or fractured central venous pressure (CVP) lines is not uncommon. Although CVP lines are usually used in seriously ill patients, often with complications secondary to prior surgical intervention, if the catheter fragments are not removed they can give rise to serious illness or death in about 50% of patients. Experience with the removal of nine such catheter fragments is reported. In eight patients a helical basket was available for removal through a Dotter retrieval catheter. With prolonged hyperalimentation therapy polyethylene catherters become very brittle. They are relatively easy to grip with the wire basket. Silicone elastomer catheters remain pliable but are so bouncy that they are difficult to grip. For removal of catheter fragments from vessels of small diameter, such as the subclavian vein, or vessels in which the catheter has to take an acute bend to enter, such as the right or left pulmonary artery, a smaller, more pliable Bean-Smith-Mahorner biliary stone helical basket was adapted by extending the length of wire to 100 cm. For removal of catheter fragments from the right pulmonary artery it is probably better to use a softer, 100-cm-long no. 8 French right heart catheter. A Dotter retriever catheter set with both large and small helical wire baskets should be available in any cardiac catheterization laboratory.


Autoantibodies to T cell costimulatory molecules in systemic autoimmune diseases.
To determine whether antilymphocyte Abs to T cell costimulatory molecules are generated in patients with autoimmune diseases and, if they exist, to clarify the mechanism of their production and pathological roles, we investigated the presence of autoantibodies to CTLA-4 (CD152), CD28, B7-1 (CD80), and B7-2 (CD86) in serum samples obtained from patients with various autoimmune diseases and from normal subjects using recombinant fusion proteins. In ELISAs, anti-CD28, anti-B7-1, and anti-B7-2 Abs were rarely seen, whereas anti-CTLA-4 Abs were detected in 8.2% of the patients with systemic lupus erythematosus, 18.8% of those with rheumatoid arthritis, 3.1% of those with systemic sclerosis, 31.8% of those with Behçet's disease, 13.3% of those with Sjögren's syndrome, and 0% of healthy donors. This reactivity was confirmed by immunoblotting. More importantly, the purified anti-CTLA-4 Abs reacted with CTLA-4 expressed on P815 cells by flow cytometry. In addition, we found at least three epitopes on the CTLA-4 molecule. Furthermore, among the patients with Behçet's disease, uveitis was seen significantly less frequently in the anti-CTLA-4 Ab-positive patients. Taken collectively, these data indicate that anti-CTLA-4 autoantibodies are generated in systemic autoimmune diseases by an Ag-driven mechanism and may modulate the immune response in vivo by binding to CTLA-4 on T cells.


Purinergic and Adenosinergic Signaling in Pancreatobiliary Diseases.
Adenosine 5'-triphosphate (ATP), other nucleotides, and the nucleoside analogue, adenosine, all have the capacity to modulate cellular signaling pathways. The cellular processes linked to extracellular purinergic signaling are crucial in the initiation, evolution, and resolution of inflammation. Injured or dying cells in the pancreatobiliary tract secrete or release ATP, which results in sustained purinergic signaling mediated through ATP type-2 purinergic receptors (P2R). This process can result in chronic inflammation, fibrosis, and tumor development. In contrast, signaling via the extracellular nucleoside derivative adenosine via type-1 purinergic receptors (P1R) is largely anti-inflammatory, promoting healing. Failure to resolve inflammation, as in the context of primary sclerosing cholangitis or chronic pancreatitis, is a risk factor for parenchymal and end-organ scarring with the associated risk of pancreatobiliary malignancies. Emerging immunotherapeutic strategies suggest that targeting purinergic and adenosinergic signaling can impact the growth and invasive properties of cancer cells, potentiate anti-tumor immunity, and also block angiogenesis. In this review, we dissect out implications of disordered purinergic responses in scar formation, end-organ injury, and in tumor development. We conclude by addressing promising opportunities for modulation of purinergic/adenosinergic signaling in the prevention and treatment of pancreatobiliary diseases, inclusive of cancer.


Value of apparent diffusion coefficient for predicting malignancy of intraductal papillary mucinous neoplasms of the pancreas.
We aimed to explore the potential value of the whole tumor apparent diffusion coefficient (ADC) for discriminating between benign and malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Forty-two patients underwent 1.5 T magnetic resonance imaging that included diffusion-weighted imaging (DWI, b=0.500 s/mm2). The mean, minimum, and maximum ADC values were measured for the whole tumor. The differences between benign and malignant IPMNs were calculated for the mean ADC, ADC-min, and ADC-max values. Receiver operating characteristics (ROC) analysis was conducted to evaluate their potential diagnostic performance. Fifteen of 25 benign IPMNs demonstrated low or iso-signal intensity on DWI with a b value of 500 s/mm2 compared with normal pancreatic parenchyma, whereas all malignant IPMNs demonstrated high signal intensity. The mean value of ADC was significantly higher in benign IPMNs compared with malignant IPMNs (3.39×10-3 mm2/s vs. 2.39×10-3 mm2/s, P < 0.001), with an area under the ROC curve (AUC) of 0.92 (95% confidence interval [CI], 0.79-0.98). The ADC-min value of malignant IPMNs was also significantly lower than that of benign IPMNs (1.24×10-3 mm2/s vs. 2.58×10-3 mm2/s, P < 0.001), with an AUC of 0.94 (95% CI, 0.82-0.99). No marked difference was found between benign and malignant IPMNs for the ADC-max value (3.89×10-3 mm2/s vs. 3.78×10-3 mm2/s, P = 0.299). Lower mean and minimum ADC values of the whole tumor might be potential predictors of malignant IPMNs of the pancreas.


Cardiovascular Risk Assessment.
Cardiovascular risk assessment is fundamental to prevention of cardiovascular disease, because it helps determine the size of the potential benefits that might accrue to individual patients from use of statins, aspirin, and other preventive interventions. Current guidelines recommend specific algorithms for cardiovascular risk assessment that combine information from traditional risk factors including blood pressure, lipids, and smoking, along with age and sex and other factors. These algorithms are the subject of active research and controversy. This article addresses the rationale, current guidelines and use, and potential future directions of cardiovascular risk assessment.


Quantifying X-Ray Fluorescence Data Using MAPS.
The quantification of X-ray fluorescence (XRF) microscopy maps by fitting the raw spectra to a known standard is crucial for evaluating chemical composition and elemental distribution within a material. Synchrotron-based XRF has become an integral characterization technique for a variety of research topics, particularly due to its non-destructive nature and its high sensitivity. Today, synchrotrons can acquire fluorescence data at spatial resolutions well below a micron, allowing for the evaluation of compositional variations at the nanoscale. Through proper quantification, it is then possible to obtain an in-depth, high-resolution understanding of elemental segregation, stoichiometric relationships, and clustering behavior. This article explains how to use the MAPS fitting software developed by Argonne National Laboratory for the quantification of full 2-D XRF maps. We use as an example results from a Cu(In,Ga)Se2 solar cell, taken at the Advanced Photon Source beamline 2-ID-D at Argonne National Laboratory. We show the standard procedure for fitting raw data, demonstrate how to evaluate the quality of a fit and present the typical outputs generated by the program. In addition, we discuss in this manuscript certain software limitations and offer suggestions for how to further correct the data to be numerically accurate and representative of spatially resolved, elemental concentrations.


Functional role of specific secreted and cell surface molecules in tumour cell invasion and metastasis.
The invasion and metastatic spread of tumour cells are complex biological processes involving an array of cell surface and secreted protein molecules which function as specific recognition and catalytic agents in each step of the malignant cascade. In order to begin to identify these molecules and implicate them as true functioning agents, our laboratory has developed selected panels of monoclonal antibodies that have been screened for their ability to inhibit specific manifestations of the malignant phenotype in various model systems. Since monoclonal antibodies recognize only single and unique determinants, it is hypothesized that any monoclonal antibody which is specifically antifunctional will allow for the identification and isolation of relevant protein molecules.


Transoral vertebroplasty for the C1 lateral mass.
Osteolytic lesions of the atlas (C1) are challenging to treat by vertebroplasty due to the vicinity of the vertebral artery and the spinal cord. To present our experience with transoral vertebroplasty (TOV) for osteolytic lesions of the lateral mass of the atlas. Retrospective case series involving 15 consecutive patients (nine male, six female, mean age 63 years) who underwent TOV for the treatment of an osteolytic lesion of the lateral mass of the atlas. Among the osteolytic lesions, 10/15 (67%) were bone metastases from various cancers; 4/15 (27%) were lesions related to multiple myeloma; and one lesion (7%) was an aggressive hemangioma. All the TOVs were performed under general anesthesia and in most cases (10/15; 67%) in a hybrid angiosuite combining a C-arm flat panel and a CT scan. The remaining five patients were treated under biplane fluoroscopic guidance. Vertebroplasty of the lateral mass of C1 through a transoral route was feasible in all cases. Significant pain relief was obtained in most cases (1 month average decrease in Numeric Rating Scale: 4.9±4.1). No major complication was recorded. In 7/15 cases (47%), cement leakage surrounding the C1 lateral mass was seen; none of these leakages had a significant clinical consequence. No additional spine surgery was required in any of the patients. TOV of osteolytic lesions of the lateral mass of the atlas is feasible and seems safe and effective, providing pain relief and bone stabilization.


The affective memory and its implications for pathodynamics.
In this paper the author presents a review of the literature concerning the connections between affective states and memory processes together with the reflections on the implications of these connections for psychopathology and symptom/syndrome formation. Especially the issue of hypermnestic states in the context of dissociative phenomena is extensively discussed. The importance of these phenomena and processes for psychotherapy is discussed too. It might well be that they are involved in symptom formation as a transference reaction as part of the process of psychotherapy.


Individual Experiences and Utilization of Supportive Resources in Adolescents and Young Adults with Cancer.
Background: Adolescents and young adults (AYAs) with cancer are often impacted by distress due to disease and treatment. Despite these concerns, prior research has found that AYAs do not utilize support resources, do not find these resources adequate, and or do not have adequate access to services. Objective: The objective of this project was to understand and identify AYA patient concerns and experiences throughout cancer treatment, what resources were utilized, how they were identified, and how supportive care resources for AYA cancer patients can be improved. Methods: Twenty-eight AYA cancer patients and survivors were interviewed on their experiences and utilization of supportive resources throughout cancer treatment. Qualitative data were analyzed using thematic analysis and organized through a priori framework examining specific domains of experience and resources utilized. Results: The most frequently discussed topic in qualitative interviews was the benefit of the health care team. Other frequently identified resources were generalized internet searches and webpages. Suggested unmet resource needs included supportive resources for family members and caregivers throughout the time of treatment. Conclusions: AYAs experience stress throughout treatment for cancer attributed to physical, practical, and psychosocial causes. Health care workers play a vital role in serving as an informative and supportive resource for their AYA patients. As such, health care workers and other supportive resources may alleviate these concerns, but these resources are still underexplored.


A gene encoding a germin-like protein, identified by a cDNA-AFLP approach, is specifically expressed during germination of Phaseolus vulgaris.
In order to identify markers of germination in Phaseolus vulgaris L., a cDNA-amplified fragment length polymorphism (AFLP) approach was conducted on mRNAs from embryo axes and from cotyledons. Among changes observed throughout the germination process, a cDNA fragment not detected 9 h after imbibition (HAI) but present specifically in axes 24 HAI was further studied. The complete cDNA was recovered by rapid amplification of cDNA ends, then cloned and sequenced. It includes an open reading frame predicting a 206-amino-acid polypeptide of 21.8 kDa. Analysis of the nucleotide sequence and deduced amino acid sequence revealed a high homology with germin-like proteins (GLPs), and particularly with an auxin-binding protein from peach, ABP19, that belongs to the GLP family. Thus, we propose that this cDNA encodes the first GLP described in P. vulgaris, designated PvGLP1. Northern blot analysis carried out on mRNAs from seed axes showed a dramatic increase in PvGLP1 expression a few hours before radicle emergence (17 HAI). Among mature vegetative tissues, PvGLP1 expression was very weak in pods and not detected in leaves, stems or roots. Immunoblot analysis using antibodies raised against AtGER3 from Arabidopsis thaliana showed that the protein could be detected only in axes from the dry seed stage onwards, at a steady-state level. Then, PvGLP1 expression seems to be associated with the early stages of embryo axis growth. The high homology indicated with ABP19 led us to study the effect of different concentrations of indole-3-acetic acid (IAA) on PvGLP1 expression during germination. Whereas no effect was noticed at low concentrations (1, 5, 10 microM), a marked decrease in PvGLP1 mRNA level was observed in axes of seeds imbibed with 100 microM IAA. Thus, PvGLP1 gene expression is not stimulated by auxin and, moreover, it might be inhibited by high concentrations of IAA.


Gut-microbiome-brain axis: the crosstalk between the vagus nerve, alpha-synuclein and the brain in Parkinson's disease.
This critical review of the literature shows that there is a close link between the microbiome, the gut, and the brain in Parkinson's disease. The vagus nerve, the main component of the parasympathetic nervous system, is involved in the regulation of immune response, digestion, heart rate, and control of mood. It can detect microbiota metabolites through its afferents, transferring this gut information to the central nervous system. Preclinical and clinical studies have shown the important role played by the gut microbiome and gut-related factors in disease development and progression, as well as treatment responses. These findings suggest that the gut microbiome may be a valuable target for new therapeutic strategies for Parkinson's disease. More studies are needed to better understand the underlying biology and how this axis can be modulated for the patient's benefit.


NAÏVE-POOLED PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID AFTER SINGLE INTRAMUSCULAR ADMINISTRATION IN SMOOTH DOGFISH (MUSTELUS CANIS).
Pharmacokinetics study of ceftiofur crystalline free acid (CCFA) was conducted in 14 adult captive smooth dogfish (Mustelus canis). A single dose of CCFA at 6.6 mg/kg was administered intramuscularly. Blood samples were collected prior to treatment and at 1, 2, 6, 12, 24, 32, 48, 72, 96, 120, 144, and 168 hr posttreatment. Naïve pooling of data from four sharks was used to generate the average plasma drug concentration at each time point. After concluding the study, additional blood samples were opportunistically collected from five randomly selected sharks at 1,920 hr. Plasma ceftiofur and desfuroylceftiofur metabolite concentrations were determined using reversed-phase high performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using a noncompartmental technique. Peak plasma concentration (Cmax) was 3.75 µg/ml with a time to Cmax (Tmax) of 96 hr. Ceftiofur plasma concentrations were maintained above 2 µg/ml for at least 168 hr and were still quantifiable at 1,920 hr.


Multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties.
This paper describes the design, fabrication, and characterization of multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. The phantoms comprise epidermis, dermis, and hypodermis skin layers, blood vessels, and blood mimicking fluid. Each tissue component may be individually tailored to a range of physiological and demographic conditions. The skin layers were constructed from varying concentrations of gelatin and agar. Synthetic melanin, India ink, absorbing dyes, and Intralipid were added to provide optical absorption and scattering in the skin layers. Bovine serum albumin was used to increase acoustic attenuation, and 40 μm diameter silica microspheres were used to induce acoustic backscatter. Phantom vessels consisting of thin-walled polydimethylsiloxane tubing were embedded at depths of 2-6 mm beneath the skin, and blood mimicking fluid was passed through the vessels. The phantoms were characterized through uniaxial compression and tension experiments, rheological frequency sweep studies, diffuse reflectance spectroscopy, and ultrasonic pulse-echo measurements. Results were then compared to in vivo and ex vivo literature data. The elastic and dynamic shear behavior of the phantom skin layers and vessel wall closely approximated the behavior of porcine skin tissues and human vessels. Similarly, the optical properties of the phantom tissue components in the wavelength range of 400-1100 nm, as well as the acoustic properties in the frequency range of 2-9 MHz, were comparable to human tissue data. Normalized root mean square percent errors between the phantom results and the literature reference values ranged from 1.06% to 9.82%, which for many measurements were less than the sample variability. Finally, the mechanical and imaging characteristics of the phantoms were found to remain stable after 30 days of storage at 21 °C. The phantoms described in this work simulate the mechanical, optical, and acoustic properties of human skin tissues, vessel tissue, and blood. In this way, the phantoms are uniquely suited to serve as test models for multimodal imaging techniques and image-guided interventions.


Protective mechanisms against oxidative stress and angiopathy in young patients with diabetes type 1 (DM1).
Advanced glycation end-products (AGEs) via their receptor, RAGE, are involved in diabetic angiopathy. Soluble RAGE, an inhibitor of this axis, is formed by enzymatic catalysis (sRAGE) or alternative splicing (esRAGE). Malondialdehyde (MDA) is an oxidative stress marker, and ferric reducing ability of plasma (FRAP) is an anti-oxidant capacity marker. In isolated mononuclear blood cells from 110 DM1-patients (P) and 124 controls (C) (4-29 years) RAGE mRNA (g) and protein expression (pe) were measured by RT-PCR and Western immunoblotting, respectively. Plasma levels of CML (AGEs) and sRAGE were measured by ELISA, MDA by flurometry and FRAP according to 'Benzie and Strain'. P showed: (i) higher g of RAGE, especially in p>13 years of age and >5 years DM1, (ii) increased pe of esRAGE in DM1>5 years and (iii) increased FRAP and MDA. The increased esRAGE and FRAP with increased levels of CML and MDA possibly reflects a protective response against the formation of diabetic complications in these young diabetic patients.


Understanding Ion Binding Affinity and Selectivity in β-Parvalbumin Using Molecular Dynamics and Mean Spherical Approximation Theory.
Parvalbumin (PV) is a globular calcium (Ca(2+))-selective protein expressed in a variety of biological tissues. Our computational studies of the rat β-parvalbumin (β-PV) isoform seek to elucidate the molecular thermodynamics of Ca(2+) versus magnesium (Mg(2+)) binding at the protein's two EF-hand motifs. Specifically, we have utilized molecular dynamics (MD) simulations and a mean-field electrolyte model (mean spherical approximation (MSA) theory) to delineate how the EF-hand scaffold controls the "local" thermodynamics of Ca(2+) binding selectivity over Mg(2+). Our MD simulations provide the probability density of metal-chelating oxygens within the EF-hand scaffolds for both Ca(2+) and Mg(2+), as well the conformational strain induced by Mg(2+) relative to Ca(2+) binding. MSA theory utilizes the binding domain oxygen and charge distributions to predict the chemical potential of ion binding, as well as their corresponding concentrations within the binding domain. We find that the electrostatic and steric contributions toward ion binding were similar for Mg(2+) and Ca(2+), yet the latter was 5.5 kcal/mol lower in enthalpy when internal strain within the EF hand was considered. We therefore speculate that beyond differences in dehydration energies for the Ca(2+) versus Mg(2+), strain induced in the β-PV EF hand by cation binding significantly contributes to the nearly 10,000-fold difference in binding affinity reported in the literature. We further complemented our analyses of local factors governing cation binding selectivity with whole-protein (global) contributions, such as interhelical residue-residue contacts and solvent exposure of hydrophobic surface. These contributions were found to be comparable for both Ca(2+)- and Mg(2+)-bound β-PV, which may implicate local factors, EF-hand strain, and dehydration, in providing the primary means of selectivity. We anticipate these methods could be used to estimate metal binding thermodynamics across a broad range of PV sequence homologues and EF-hand-containing, Ca(2+) binding proteins.


Characterization of the potassium channel from frog skeletal muscle sarcoplasmic reticulum membrane.
1. The sarcoplasmic reticulum (SR) membrane of skeletal muscle contains potassium channels which are thought to support charge neutralization during calcium release by providing a permeability pathway for counter-ion movement. To describe the behaviour of the SR K+ channel under physiological conditions, single channel activity was recorded from excised patches of SR membrane. Patches were made from membrane blebs extruded from contracted muscle fibres whose surface membranes had been removed previously by mechanical dissection. 2. The channel was active over a large voltage range from -80 to +100 mV. The current-voltage relationship of the channel was linear over most of this voltage range (slope conductance equal to 60 pS in 130 mM potassium), but showed rectification at voltages below -50 mV. 3. The activity of the channel (number of state transitions per unit time) was greater at positive voltages than at negative voltages. Analysis of dwell-time distributions showed that the time spent in the open state is best fitted by a double Gaussian, suggesting that the channel possesses both a long (l)- and a short (s)-lived open state with identical conductances. The dwell times for the two states were Ts = 0.3 ms and Tl = 2.6 ms at +90 mV and Ts = 0.1 ms and Tl = 15.1 ms at -40 mV. Thus, positive voltage decreased the long open time significantly which was consistent with the observed increase in channel activity at positive potentials. 4. The permeability sequence of the channel to various monovalent cations was deduced from the channel reversal potential under bi-ionic conditions and was found to be: K+ > Rb+ > Na+ > Cs+ > Li+. 5. Channel activity was reduced when the patch was perfused with 1,10-bis-guanidino-n-decane (BisG10), a drug reported to block the SR K+ channel with high affinity. The drug concentration necessary to reduce the open probability (P(o)) by 50% was 19.8 microM at -40 mV and 338.2 microM at +50 mV. The zero voltage dissociation constant (Kd) was calculated to be 48 microM. 6. Pharmacological agents known to affect surface membrane K+ channels, such as 0.5 mM Ba2+ or 3.0 mM 4-aminopyridine, were much less effective in blocking the channel than BisG10. Physiological calcium concentrations (pCa = 8.0 and 3.0) did not affect channel behaviour.4


Retinocytoma: A Case Series.
Retinoblastoma is the most common ocular malignancy in children, considered fatal without treatment. Retinocytoma is a rare benign clinical entity of retinoblastoma that shows signs of tumor regression. The clinical presentation of retinocytoma usually includes a gray translucent mass, intralesional calcification, and retinal pigment epithelial alteration, along with the presence of chorioretinal atrophy. We report two cases of retinocytoma in patients presenting with strabismus in the Eastern Province of Saudi Arabia.


[Risk factors for death and the clinical features of different subtypes of patients with pulmonary arterial hypertension related to congenital heart disease].
Objective: To explore the risk factors for death in patients with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) and the clinical characteristics of different subtypes in patients with PAH-CHD. Methods: It was a retrospective study. A total of 507 PAH-CHD patients, who were hospitalized in the Department of Pediatric Cardiology of Beijing Anzhen Hospital between September 2005 and May 2019, were included. Patients were divided into 4 subgroups: (1) Eisenmenger syndrome(ES) group. (2) PAH associated with prevalent systemic-to-pulmonary shunts(SP) group. (3) PAH associated with small defects(SD) group. (4) PAH after defect correction(CD) group. According to the complexity of cardiac malformation, patients were divided into simple-medium complex malformation group and complex malformation group. According to the location of shunts, patients were divided into pre-tricuspid group, post-tricuspid group, and mixed group or complex deformity group. Baseline clinical data of patients were collected from the electronic medical record system. Demographic data (age, gender, etc.), percutaneous oxygen saturation(SPO(2)), New York Heart Association(NYHA) cardiac function classification, 6 minutes walking distance(6MWD), and B type natriuretic peptide(BNP), systolic pulmonary arterial pressure(sPAP) estimated by echocardiography and mean pulmonary artery pressure (mPAP), mean right atrial pressure(mRAP), cardiac index(CI), and calculated pulmonary vascular resistance (PVR) estimated by right heart catheterization were compared among various groups. The results of regular follow-up of all enrolled patients were collected, including the status of monotherapy or combination of PAH-targeted drugs during the follow-up period, cardiac-related adverse events(hemopysis, syncope, edema, arrhythmia, etc.) and primary endpoint event(all-cause death) were obtained and analyzed. Risk factors for all-cause death were analyzed using univariate and multivariate Cox regression analysis model. Results: The median age at diagnosis was 23.1(13.9,32.1) years, 345 cases(68.0%) were female. Two hunderds and thirty-five cases(46.4%) were diagnosed with ES; 193 cases(38.1%) were diagnosed with CD, 47 cases (9.3%) were diagnosed with SD. Among them, 32 cases(6.3%) were in the SP group. All 507 patients underwent echocardiography examination, there were significant differences in sPAP among different clinical subgroups(P<0.001). A total of 289 patients(57.0%) received right heart catheterization examination, the results showed that the ES group had the highest mPAP and PVR and the lowest mRAP(all P<0.001), the CD group had the highest mRAP and CI(both P<0.001). The 6MWD in the ES group was significantly shorter than that in the SP, SD, and CD groups(all P<0.001). The proportion of patients with NYHA class Ⅲ/Ⅳ was higher in SD group than in SP group(P<0.001), which was similar between SD, ES and CD groups (P values were 0.077 and 0.072, respectively). At admission, the proportion of patients with NYHA class Ⅰ/Ⅱwas the highest in SP group(96.9% (31/32) ), followed by CD group (85.5%(165/193)) and the ES group(85.1%(200/235)), and the SD group(75.0%(35/47)). The BNP level at admission was also higher in SD group than in SP, ES and CD groups(P<0.001). Of the 507 patients, 379(74.8%) patients received PAH-targeted drug therapy at the last follow-up, and the treatment plan was mainly monotherapy(75.7%(287/379)). The median follow-up time was 3.6(2.0, 5.6) years and 37(7.3%) patients died, including 13 in the CD group, 17 in the ES group, and 7 in the SD group. No deaths occurred in the SP group. Right heart failure was the most common cause of death(11(29.7%)), followed by severe hemoptysis dyspnea(7(18.9%)), sudden cardiac death(6(16.2%)), and pulmonary hypertensive crisis(4(10.8%)). Kaplan-Meier curve showed that survival rates of end-point-free events at 1, 3, 5 and 10 years after diagnosis of PAH were 98.0%, 95.4%, 89.9%, and 84.4%, respectively; there were statistically significant differences in survival among the subgroups(P=0.026); there was no significant difference in the survival rate between the ES group and the CD group(P=0.918), and both were higher than the SD group(P values were 0.011 and 0.013, respectively). Univariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ and BNP>100 ng/L at admission were the risk factors for all-cause death in patients with PAH-CHD(HR=6.452, 95%CI 3.378-12.346, P<0.001, and HR=2.481, 95%CI 1.225-5.025, P=0.012). Multivariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ was an independent risk factor for all-cause death in patients with PAH-CHD(HR=4.998, 95%CI 1.246-20.055, P=0.023). Conclusions: PAH-CHD patients with different clinical subtypes have different clinical symptoms, cardiac functional class, hemodynamic characteristics, and mid to long-term survival rates. SP patients have the best prognosis, outcome of ES and CD patients is similar, and SD patients have the worst prognosis. NYHA class Ⅲ/Ⅳ is an independent risk factor for all-cause death in patients with PAH-CHD.


On the active principles of the spurge family (Euphorbiaceae). V. Extremely skin-irritant and moderately tumor-promoting diterpene esters from Euphorbia resinifera Berg.
The irritant and tumor-promoting principles were isolated from the latex of Euphorbia resinifera Berg. and from the resin derived from latex (euphorbium), which is commercially available as a drug. The irritant Euphorbia factors RL 5 (mixture), RL 6, RL 7, RL 8, and RL 10 were identified as tigliane-type 12-deoxyphorbol esters each bearing, in the 13 position, either long-chain, partially methyl-substituted acyl residues (10-16 carbon atoms) or short-chain acyl residues (4 or 5 carbon atoms) or a (substituted) phenylacetyl group with a 20-acetoxy group. Euphorbia factors RL 15 (mixture), RL 16, RL 17, RL 18, and RL 21 are the corresponding 20-deacetylated derivatives thereof. The irritant Euphorbia factors RL 11, RL 12, RL 22, RL 23 were characterized as esters of the tigliane type 12-deoxy-16-hydroxyphorbol, i.e., 13-0-phenylacetyl-16-0-benzoyl-12-deoxy16-hydroxyphorbol-20- acetate (RL 11) and 13, 16-0-phenylacetyl, tigloyl-12-deoxy-16-hydroxy-phorbol-20-acetate (RL 12), RL 22 and RL 23 representing the respective 20-deacetylated derivatives. A mixture of irritant factors, RL 13, was shown to represent long-chain 3-esters of ingenane-type ingenol with similar acyl residues (10-16 carbon atoms, partially methyl-substituted) to RL 5 (RL 15) above. A further group of E. resinifera factors was of the daphnane type: RL 9 was identified as the extremely irritant 9,13,14-orthophenylacetate of resiniferonol-20-(4-hydroxy-3-methoxy)phenylacetate (Resiniferatoxin), RL 14 as the corresponding 9,13,14-orthophenylacetate of resiniferonol, and RL 20 as 14-0-phenylacetylresiniferonol-20-(4-hydroxy-3-methoxy)-phenylacet ate (Proresiniferatoxin). The irritant factors specified below were accompanied by nonirritant esters of the tigliane type 12,20-dideoxyphorbol, i.e., RL 1 and RL 2, and of the lathyrane type ingol, i.e., RL 3 and RL 4. In tumor promotion experiments the mixture of homologous irritant factors RL 13 was equipotent with the standard tumor promoter TPA, but at 10 times the dose of TPA. Several others of the irritant factors had low activity as tumor promotors, but of the few tumors obtained in these experiments a high percentage was malignant. The very high irritant activity of the latex may be ascribed to resiniferatoxin (RL 9), representing a new class of rapidly acting skin irritants. No promoting activity was detected on administration of the highly irritant resiniferatoxin.


Variants in immune-related genes and genital HPV 16 persistence in men.
While most human papillomavirus (HPV) infection clears on its own, persistent HPV infection can cause genital warts and anal, penile and oropharyngeal cancers in men. We conducted genetic analysis in a sub-cohort of the HPV infection in men (HIM) study to test the hypothesis that differences in host genes influence HPV persistence in men. Baseline and longitudinal genital HPV status at the genitals was measured every 6-months using the Linear Array assay amplified HPV L1 gene fragment using the PGMY09/11 L1 consensus primer system. DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) in the customized genome-wide genotyping array, the "TxArray," were examined using logistic regression in a case-control study design to assess the association with HPV16 persistence/clearance. Of the total of 737,742 autosomal SNPs in the array, 605,885 passed basic quality control and were examined between 40 men (cases) with > 18 months persistent genital HPV 16 infection vs. 151 controls who were HPV 16-positive, but whose infections cleared in < 18 months. The logistic regression analysis from this case-control study showed variants in several gene regions associated with genital HPV 16 persistence, with the strongest association detected with SNPs on chromosomes 20 (p < 5.72 × 10-6) and 15 (p < 5.89 × 10-6), after adjusting for age, smoking status, number of sex partners and four principal components (ancestral background). Our results provide a preliminary basis for understanding the biological mechanism of oncogenic HPV 16 pathogenesis at the genitals in men. Some of the genes flanking the top hit SNPs are consistent with previous findings in both HPV related and non-related cancers but further genetic studies in larger cohorts are warranted to confirm these and identify novel major susceptibility genes involved in the pathogenesis of genital HPV persistence in men.


Prevalence of prescription and illicit drugs in pregnancy-associated non-natural deaths of Florida mothers, 1999-2005.
Abuse of prescription and illicit drugs has been rapidly increasing. This study examines the prevalence of drug use in the non-natural deaths of pregnant or recently pregnant women. Records from Florida's Pregnancy Associated Mortality Review conducted between 1999 and 2005 (n = 415) were linked to 385 toxicology reports obtained from Florida medical examiners' offices. The final study sample consisted of 169 drug-positive, pregnancy-associated non-natural deaths. Of these, 86 were positive for both blood and urine, 64 were positive for blood only and five for urine only, and the remainder were positive for some other specimen. Among these deaths, 91 cases (54%) involved prescription drugs, 78 cases (46%) involved illicit drugs, and 69 cases (41%) involved alcohol. Opioids constituted the majority of deaths associated with prescription drugs. Substantial co-use of opioids and benzodiazepines was seen. Pregnant or recently pregnant women may have more interactions with healthcare providers, which may present more opportunities for intervention and prevention.


[The effect of immunomodulators on the functional activity of polymorphonuclear leukocytes from the peripheral blood of healthy subjects in vitro].
The effect of such immunomodulators as glucoaminylmuramyldipeptide, gamma-interferon and polyoxydonium on the functional activity of phagocytic cells of peripheral blood taken from 33 healthy donors was studied. The adhesion of these cells on the plastic surface, their spontaneous and induced luminol-dependent chemiluminescence, the activity of myeloperoxidase and acidic phosphatase and changes in the activity of enzymes after the in vitro stimulation of the cells, the results of the spontaneous and induced nitro blue tetrazolium test, chemotaxis of neutrophils and the content of nonenzymatic cation proteins in neutrophils were determined. The study revealed considerable differences in the effect produced by the above-mentioned immunomodulating preparations on some manifestations of the phagocyte reactiveness in the examined subjects. Only in 30.0% of cases similar in vitro sensitivity of cells to two or all three preparations was registered, and in 15.2% of cases no stimulating effect was noted. Peripheral blood neutrophils are supposed to have individual sensitivity to certain immunostimulators.


N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial.
Mechanism-based treatments for schizophrenia are needed, and increasing evidence suggests that oxidative stress may be a target. Previous research has shown that N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor almost devoid of side effects, improved negative symptoms, decreased the side effects of antipsychotics, and improved mismatch negativity and local neural synchronization in chronic schizophrenia. In a recent double-blind randomized placebo-controlled trial by Conus et al., early psychosis patients received NAC add-on therapy (2700 mg/day) for 6 months. Compared with placebo-treated controls, NAC patients showed significant improvements in neurocognition (processing speed) and a reduction of positive symptoms among patients with high peripheral oxidative status. NAC also led to a 23% increase in GSH levels in the medial prefrontal cortex (GSHmPFC) as measured by 1H magnetic resonance spectroscopy. A subgroup of the patients in this study were also scanned with multimodal MR imaging (spectroscopy, diffusion, and structural) at baseline (prior to NAC/placebo) and after 6 months of add-on treatment. Based on prior translational research, we hypothesized that NAC would protect white matter integrity in the fornix. A group × time interaction indicated a difference in the 6-month evolution of white matter integrity (as measured by generalized fractional anisotropy, gFA) in favor of the NAC group, which showed an 11% increase. The increase in gFA correlated with an increase in GSHmPFC over the same 6-month period. In this secondary study, we suggest that NAC add-on treatment may be a safe and effective way to protect white matter integrity in early psychosis patients.


Next-generation Sequencing Reveals Age-dependent Genetic Underpinnings in Lung adenocarcinoma.
Background: More than 40% of lung cancer patients are diagnosed at ages over 70. However, the genomic and clinical characteristics among them remain elusive. Here, we performed targeted capture sequence to characterize the mutational spectrum of Chinese lung adenocarcinoma (LUAD) patients across ages. Patients and Methods: 2025 LUAD patients were divided into three groups: young (≤50 years old) (n=416, 20.54%), intermediate (51~69 years old) (n=1271, 62.77%), and aged (≥70 years old) (n=338, 16.69%). 1,021-gene panel and 59-gene panel were used for sequencing with tissue samples. Genetic alterations and tumor mutation burden (TMB) in LUAD patients were investigated. Results: The frequency of mutations affecting 20 genes were significantly higher in aged group than in young group, and fourteen of them were not reported before, including involved in cell cycle/apoptosis signaling (FAT1, FAT2), DNA damage repair (FANCA and FANCM), chromatin histone modification (KDM6A), RTK/RAS/PI3K signaling (FLT4 and MTOR), NOTCH signaling (NOTCH1, NOTCH2 and NOTCH4) and other signaling pathway or cellular regulatory factor (KEAP1, ASXL1, EPHB1 and ABCB1). Six previously reported mutated genes (RBM10, KRAS, LRP1B, CDKN2A and KMT2C/D) were also significantly more frequent in aged group. Among clinical actionable mutation sites, KRAS mutation was presented more common in aged group; both MET exon 14 skipping and MET amplification were significantly positively correlated with old age; the fusions of ALK, ROS1, RET and ERBB2 exon 20 insertion were less frequent in aged group. Furthermore, a higher level of TMB was found in aged group compared with young group. Conclusion: In this study, we revealed the differences of somatic genetic mutations and TMB between young and aged LUAD patients, which may provide directions of targeted therapy and advantages of immunotherapy for the elderly in the future.


Tension pneumothorax complicated by double-lumen endotracheal tube intubation.
Tension pneumothorax is not a rare complication of mechanical ventilation, but its occurrence immediately after intubation with a double-lumen endotracheal tube (DLT) is very rare. Subsequent impairment of the respiratory and cardiovascular function can be life threatening if it is not detected early enough and managed properly. Most reported cases of tension pneumothorax during DLT intubation occurred when one-lung ventilation was applied. Herein we report a case of tension pneumothorax and pneumoperitoneum which occurred immediately after DLT intubation. It appeared before one-lung ventilation was applied because of an inappropriately small-sized and malpositioned DLT.


Human Testis Extracellular Matrix Enhances Human Spermatogonial Stem Cell Survival In Vitro.
This study developed and characterized human testis extracellular matrix (htECM) and porcine testis ECM (ptECM) for testing in human spermatogonial stem cell (hSSC) culture. Results confirmed the hypothesis that ECM from the homologous species (human) and homologous tissue (testis) is optimal for maintaining hSSCs. We describe a simplified feeder-free, serum-free condition for future iterative testing to achieve the long-term goal of stable hSSC cultures. To facilitate analysis and understand the fate of hSSCs in culture, we describe a multiparameter, high-throughput, quantitative flow cytometry approach to rapidly count undifferentiated spermatogonia, differentiated spermatogonia, apoptotic spermatogonia, and proliferative spermatogonia in hSSC cultures.


Coexistence of Multiple Types of Synaptic Plasticity in Individual Hippocampal CA1 Pyramidal Neurons.
Understanding learning and memory mechanisms is an important goal in neuroscience. To gain insights into the underlying cellular mechanisms for memory formation, synaptic plasticity processes are studied with various techniques in different brain regions. A valid model to scrutinize different ways to enhance or decrease synaptic transmission is recording of long-term potentiation (LTP) or long-term depression (LTD). At the single cell level, spike timing-dependent plasticity (STDP) protocols have emerged as a powerful tool to investigate synaptic plasticity with stimulation paradigms that also likely occur during memory formation in vivo. Such kind of plasticity can be induced by different STDP paradigms with multiple repeat numbers and stimulation patterns. They subsequently recruit or activate different molecular pathways and neuromodulators for induction and expression of STDP. Dopamine (DA) and brain-derived neurotrophic factor (BDNF) have been recently shown to be important modulators for hippocampal STDP at Schaffer collateral (SC)-CA1 synapses and are activated exclusively by distinguishable STDP paradigms. Distinct types of parallel synaptic plasticity in a given neuron depend on specific subcellular molecular prerequisites. Since the basal and apical dendrites of CA1 pyramidal neurons are known to be heterogeneous, and distance-dependent dendritic gradients for specific receptors and ion channels are described, the dendrites might provide domain specific locations for multiple types of synaptic plasticity in the same neuron. In addition to the distinct signaling and expression mechanisms of various types of LTP and LTD, activation of these different types of plasticity might depend on background brain activity states. In this article, we will discuss some ideas why multiple forms of synaptic plasticity can simultaneously and independently coexist and can contribute so effectively to increasing the efficacy of memory storage and processing capacity of the brain. We hypothesize that resolving the subcellular location of t-LTP and t-LTD mechanisms that are regulated by distinct neuromodulator systems will be essential to reach a more cohesive understanding of synaptic plasticity in memory formation.


Mechanism and requirements of in vitro RNA splicing of the primary transcript from the T4 bacteriophage thymidylate synthase gene.
The splicing of a procaryotic precursor RNA transcribed from the T4 phage thymidylate synthase (td) gene with SP6 RNA polymerase was investigated in vitro. The intron excision-cyclization reaction increased progressively to 60 degrees C. Exon ligation, though barely detectable at the lower temperatures, was greatly enhanced at 60 degrees C. Both reactions required Mg2+. The addition of guanosine to the 5' end of an intron-exon II intermediate via a 3',5'-phosphodiester bond was essential for the ligation of exon I to exon II. The added guanosine and the first intron-encoded uridine are subsequently lost as a dinucleotide from the 5' end during cyclization of the linear form of the excised intron RNA. Exon ligation is intramolecular and occurs more readily in the nascent RNA molecule (cotranscriptionally) than in the finished transcript (posttranscriptionally). These data and the identification of various structural elements (P, Q, R, S, E, E') in the td intron that are found typically in eucaryotic class I introns firmly establish the td intron as the first example of class I intron of procaryotic origin.


Some Nereididae (Annelida: Polychaeta) from the Pacific Coast of Costa Rica.
Fifteen species of Nereididae (Annelida: Polychaeta) belonging to nine genera are reported from the subtidal and intertidal of the Pacific Coast of Costa Rica. A new species, Nereis costaricaensis, is described. Laeonereis brunnea Hartmann-Schröder 1959 is removed from synonomy with L. culveri (Webster 1880) while Perinereis seridentata (Hartmann-Schröder 1959) is moved from the genus Neanthes based upon the presence of bar-shaped paragnaths on area VI of the proboscis. The presence of Neanthes micromma Harper 1979 is an extension of the range of this species from the Gulf of California and Neanthes roosevelti Hartman 1939 is the first record of this species since its description from the Galapagos. A taxonomic key to these nereidid species is included.


Immunocytochemical localization of mouse placental lactogen in the mouse placenta.
The localization of mouse placental lactogen (mPL) in the mouse placenta has been examined with the avidin-biotin-peroxidase complex (ABC) technique. Staining was observed to occur in the basal zone of placentae from days 10, 12, 15, and 18 of gestation. Within the basal zone, the most prominent staining was localized to the cytoplasm of the giant cells. Within the labyrinth, staining was observed in the giant cells in day-15 and day-18 placentae, with a greater number of stained cells being observed in the latter.


Cannabinoid Receptors, Mental Pain and Suicidal Behavior: a Systematic Review.
The current serotonin-based biological model of suicidal behavior (SB) may be too simplistic. There is emerging evidence that other biomarkers and biological systems may be involved in SB pathophysiology. The literature on the endocannabinoid (EC) systems and SB is limited. The objective of the present article is to review all available information on the relationship between cannabinoid receptors (CB1 and CB2 receptors), and SB and/or psychological pain. Our review is limited by the small number and heterogeneity of studies identified: (1) an autopsy study describing elevated levels of CB1 receptor activity in the prefrontal cortex and suicide in both depression and alcoholism and (2) studies supporting the involvement of both CB1 and CB2 receptors in the regulation of neuropathic pain and stress-induced analgesia. We conclude that cannabinoid receptors, particularly CB1 receptors, may become promising targets for the development of novel therapeutic tools for the treatment of SB.


Effects of acute exercise on visual reaction time.
We examined the effects of acute exercise on reaction time to visual stimuli presented in the central portion and periphery of the visual field. Twelve participants performed reaction time tasks at rest and during cycling at 65 % peak oxygen uptake in two visual conditions. We used circular black-and-white checkerboard patterns as visual stimuli. The participants were asked to respond as quickly as possible to pattern reversal of the visual stimulus by releasing a response button. Reaction time was fractionated into Premotor time and Motor time. Premotor time in the peripheral condition significantly increased (p < 0.025) during exercise (mean +/- SE; 195.9 +/- 7.9 ms) from that at rest (183.7 +/- 6.8 ms). Premotor time in the central condition did not differ between at rest (185.3 +/- 7.6 ms) and during exercise (188.4 +/- 6.6 ms). These data suggest that the ability to respond to visual stimuli presented in the periphery of the visual field is vulnerable to moderate to severe exercise, as compared with the ability to respond to visual stimuli presented in the central portion of the visual field. An exercise-induced increase in arousal level and a consequent narrowing of attentional focus would explain the present results.


[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis].
Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction. To evaluate the feasibility and safety of sedation using dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction. Thirty consecutive cases of percutaneous arterial chemoembolization for hepatocellular carcinoma with hepatitis C-related cirrhosis(male, 23; female, 7; age, 74±5.9; weight, 62.7±12.3 kg; Child-Pugh A, 23; Child-Pugh B, 7)were analyzed retrospectively. Dexmedetomidine was administered at 3 mg/kg/h for 15 minutes as the initial loading dose and at 0.4 mg/kg/h as the maintenance dose. The sedation level was evaluated using the Ramsay sedation scale. In 30 of 30 cases, percutaneous arterial chemoembolization therapy could be performed with dexme- detomidine sedation. In 27 of 30 cases, the procedure was completed with the maintenance dose of 0.4 mg/kg/h. In 3 of 30 cases, the maintenance dose was increased to 0.6 mg/kg/h because of patient body motion. The mean administration time of dexmedetomidine was 82±30 minutes. The level of sedation measured with the Ramsay sedation scale at the end of the procedure was 3 points in 29 cases and 5 points in one case. Adverse events occurred in 3 of 30 cases. Intravenous drip leakage occurred in one case, vertigo occurred in one case, and vomiting occurred in one case. There were no adverse events requiring treatment. Sedation with dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction was feasible and safe.


Neuronal apoptosis does not play an important role in human rabies encephalitis.
It is generally accepted that there are not prominent features of neuronal cell death in rabies encephalitis. However, Hemachudha and coworkers recently reported widespread apoptosis in the central nervous system of several human rabies cases (BMC Infect Dis 5: 104, 2005). In this study we have evaluated morphological features and markers of neuronal apoptosis in postmortem brain tissue from 12 cases of human rabies who died in four different countries. Histopathological analysis, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) staining, and immunostaining for cleaved (activated) caspase-3 were performed on paraffin-embedded tissues from the cerebral cortex, hippocampus, and brainstem, and additional regional areas from one of the cases. We did not find morphological evidence of neuronal apoptosis or TUNEL staining in any of the cases of rabies encephalitis. Similarly, immunostained cleaved caspase-3 was not seen in neurons, but prominent staining was observed in microglial processes. We conclude that neuronal apoptosis does not play an important pathogenetic role in human rabies encephalitis.


[Abdominal sonography in small animals. I. Physical fundamentals, apparatus technic].
Ultrasound waves result from the utilization of the reverse "piezo-electric effect". The diagnostic ultrasound uses the impulse-echo method. Interfaces between tissues of differing acoustic impedance reflect part or all of the sound beam back towards the transducer. The returning echos are converted into electrical signals, which are analysed according to the strength and depth of reflection and finally displayed on a monitor as amplitudes or brightness values. Scanning is performed with mechanical sector or electrical linear array transducers. The pros and cons of the different scanners are discussed and at least some advice for the choice of an ultrasound machine is given.


Immunosuppressive effects of CCL17 on pulmonary antifungal responses during pulmonary invasive aspergillosis.
Aspergillus fumigatus-sensitized CCR4-deficient (CCR4-/-) mice exhibit an accelerated clearance of conidia during fungal asthma. In the present study, we examined the roles of CCL17 and CCL22, two CCR4 ligands, during pulmonary invasive aspergillosis in neutropenic mice. Kaplan-Meier survival curve analysis revealed that wild-type C57BL/6 (CCR4+/+) mice were significantly protected from the lethal effects of Aspergillus compared with their wild-type controls following systemic neutralization with anti-CCL17 but not anti-CCL22 antibodies. Systemic neutralization of CCL17 significantly increased whole-lung CCL2 levels. Mouse survival and histological analysis revealed that the receptor mediating the deleterious effects of CCL17 was CCR4 since mice genetically deficit in CCR4 (CCR4-/-) did not develop invasive aspergillosis. Enzyme-linked immunosorbent assay analysis of whole-lung samples at day 2 after conidial challenge in neutrophil-depleted CCR4-/- and CCR4+/+ mice revealed that whole-lung IL-12 levels were significantly increased in the CCR4-/- group compared with the wild-type group. Also at day 2 after conidial challenge, significantly greater numbers of CD11c+ F4/80+ and CD11c+/CD86+ but fewer CD3/NK1.1+ cells were present in the lungs of CCR4-/- mice compared with their wild-type counterparts. Thus, CCL17-CCR4 interactions dramatically impair the pulmonary antifungal response against A. fumigatus in neutropenic mice.


The stochastic nature of action potential backpropagation in apical tuft dendrites.
In cortical pyramidal neurons, backpropagating action potentials (bAPs) supply Ca2+ to synaptic contacts on dendrites. To determine whether the efficacy of AP backpropagation into apical tuft dendrites is stable over time, we performed dendritic Ca2+ and voltage imaging in rat brain slices. We found that the amplitude of bAP-Ca2+ in apical tuft branches was unstable, given that it varied from trial to trial (termed "bAP-Ca2+ flickering"). Small perturbations in dendritic physiology, such as spontaneous synaptic inputs, channel inactivation, or temperature-induced changes in channel kinetics, can cause bAP flickering. In the tuft branches, the density of Na+ and K+ channels was sufficient to support local initiation of fast spikelets by glutamate iontophoresis. We quantified the time delay between the somatic AP burst and the peak of dendritic Ca2+ transient in the apical tuft, because this delay is important for induction of spike-timing dependent plasticity. Depending on the frequency of the somatic AP triplets, Ca2+ signals peaked in the apical tuft 20-50 ms after the 1st AP in the soma. Interestingly, at low frequency (<20 Hz), the Ca2+ peaked sooner than at high frequency, because only the 1st AP invaded tuft. Activation of dendritic voltage-gated Ca2+ channels is sensitive to the duration of the dendritic voltage transient. In apical tuft branches, small changes in the duration of bAP voltage waveforms cause disproportionately large increases in dendritic Ca2+ influx (bAP-Ca2+ flickering). The stochastic nature of bAP-Ca2+ adds a new perspective on the mechanisms by which pyramidal neurons combine inputs arriving at different cortical layers.NEW & NOTEWORTHY The bAP-Ca2+ signal amplitudes in some apical tuft branches randomly vary from moment to moment. In repetitive measurements, successful AP invasions are followed by complete failures. Passive spread of voltage from the apical trunk into the tuft occasionally reaches the threshold for local Na+ spike, resulting in stronger Ca2+ influx. During a burst of three somatic APs, the peak of dendritic Ca2+ in the apical tuft occurs with a delay of 20-50 ms depending on AP frequency.


MAPS Database: Medicinal plant Activities, Phytochemical and Structural Database.
Drug development from natural sources is an important and fast developing area. Natural sources (plants) have been used to cure a range of diseases for Thousands of years. Different online medicinal plant databases provide information about classifications, activities, phytochemicals and structure of phytochemicals in different formats. These databases do not cover all aspects of medicinal plants. MAPS (Medicinal plant Activities, Phytochemicals & structural database) has been constructed with uniqueness that it combines all information in one web resource and additionally provides test targets on which particular plant found to be effective with reference to the original paper as well. MAPS database is user friendly information resource, including the data of > 500 medicinal plants. This database includes phytochemical constituents, their structure in mol format, different activities possessed by the medicinal plant with the targets reported in literature. http://www.mapsdatabase.com.