Mass spectral measurements of the apoHDL in horse (Equus caballus) cerebrospinal fluid.
As a continuation of our proteogenomic studies of equine apolipoproteins, we have obtained molecular masses for several of the apolipoproteins associated with the HDL in horse cerebrospinal fluid (CSF). Using electrospray-ionization mass spectrometry (ESI-MS), we report on values for apolipoproteins, A-I and A-II, as well as acylated apoA-I. In comparison with our previously published data on equine plasma apolipoproteins, there appears to be a higher percentage of acylated apoA-I in the CSF than in plasma. As was the case in plasma, apoA-II circulates as a homodimer. These studies also revealed a protein with a mass of 34,468Da that we are speculating is the value for horse apoE.


Taxonomic investigation of the zooplanktivorous Lake Malawi cichlids Copadichromis mloto (Iles) and C. virginalis (Iles).
The taxonomic status of the zooplanktivorous cichlids Copadichromis mloto and C. virginalis has been confused since their original descriptions by lles in 1960. Whilst two forms of C. virginalis, 'Kaduna' and 'Kajose', were distinguished in the type material, C. mloto has not been positively identified since its original description. Here we re-examined the types as well as 54 recently collected specimens from multiple sampling locations. Genome sequencing of 51 recent specimens revealed two closely related but reciprocally monophyletic clades. Geometric morphological analysis indicated that one clade morphologically encompasses the type specimens of C. virginalis identified by Iles as the Kaduna form, including the holotype, whilst the other clade encompasses not only the paratypes identified as the Kajose form, but also the type series of C. mloto. Given that all three forms in Iles's type series are from the same locality, that there are no meristic or character states to differentiate them and that there are no records of adult male C. mloto in breeding colours, we conclude that the Kajose form previously identified as C. virginalis represents relatively deeper bodied sexually active or maturing individuals of C. mloto. The online version contains supplementary material available at 10.1007/s10750-022-05025-1.


Synthesis of fused bicyclic aminals through sequential gold/Lewis acid catalysis.
A novel sequential catalysis by combining gold catalysis with early transition metal catalysis was developed. Biologically important bicyclo[4.n.0] aminals were obtained under very mild conditions.


Characterization of pallidonigral neurons in the rat by a combination of Golgi impregnation and retrograde transport of horseradish peroxidase: their monosynaptic input from the neostriatum.
After injection of horseradish peroxidase, or its conjugate with wheatgerm agglutinin, into the substantia nigra of rats, retrogradely labelled cells were found in the globus pallidus. Forty-six of these neurons were also impregnated by the Golgi procedure and then gold-toned: their somata ranged from 15 to 30 microns in diameter and these pallidonigral neurons had from two to five primary dendrites that were long and smooth, that branched infrequently and that bore occasional spines on their distal regions. Most of the neurons studied came from the lateral part of the globus pallidus. At the ultrastructural level, the identified pallidonigral neurons were found to have deeply infolded nuclei and an abundant cytoplasm; their perikarya were richly innervated by two distinct types of bouton, both of which formed symmetrical synaptic contacts. The dendrites of pallidonigral neurons were ensheathed in boutons, the majority forming symmetrical synaptic contacts. After placement of electrolytic lesions in the rostro-dorsal neostriatum, degenerating boutons were found in symmetrical synaptic contact with the cell bodies and dendrites of six identified pallidonigral neurons. It is concluded that pallidonigral neurons belong to the Golgi category of large pallidal neurons with smooth dendrites and that they receive monosynaptic input from the neostriatum. Thus, in addition to the direct striatonigral pathway, the neostriatum can influence the substantia nigra by a monosynaptic relay through the globus pallidus, which might allow other pallidal afferents to influence the transfer of information from neostriatum to substantia nigra.


Choroidal blood flow measured in the dog eye in vivo and in vitro by local hydrogen clearance polarography: validation of a technique and response to raised intraocular pressure.
Local choroidal flow has been measured using hydrogen (H2) clearance polarography in dog eyes in vivo and in vitro. The accuracy and reproducibility of the method was checked in the eye in vitro by demonstrating a linear relationship between flow measurements obtained by an absolute method and those obtained by the H2 clearance technique. The H2 electrode was placed through a scleral window and its current response to a bolus injection of H2-saturated saline into a proximal artery was measured. The clearance of H2 from the choroidal circulation in vitro was monoexponential and the reproducibility of the measurements at the same site and in the same eye was good. In vivo the technique was used to measure alterations in local choroidal blood flow produced by acute changes of intraocular pressure. A linear relationship between perfusion pressure and choroidal blood flow was obtained. H2 clearance polarography is shown to be an accurate and reproducible method for determining choroidal flow, with the advantage that localized repeated measurements of flow can be made.


Combination anti-HIV antibodies provide sustained virological suppression.
Antiretroviral therapy is highly effective in suppressing human immunodeficiency virus (HIV)1. However, eradication of the virus in individuals with HIV has not been possible to date2. Given that HIV suppression requires life-long antiretroviral therapy, predominantly on a daily basis, there is a need to develop clinically effective alternatives that use long-acting antiviral agents to inhibit viral replication3. Here we report the results of a two-component clinical trial involving the passive transfer of two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074. The first component was a randomized, double-blind, placebo-controlled trial that enrolled participants who initiated antiretroviral therapy during the acute/early phase of HIV infection. The second component was an open-label single-arm trial that enrolled individuals with viraemic control who were naive to antiretroviral therapy. Up to 8 infusions of 3BNC117 and 10-1074, administered over a period of 24 weeks, were well tolerated without any serious adverse events related to the infusions. Compared with the placebo, the combination broadly neutralizing monoclonal antibodies maintained complete suppression of plasma viraemia (for up to 43 weeks) after analytical treatment interruption, provided that no antibody-resistant HIV was detected at the baseline in the study participants. Similarly, potent HIV suppression was seen in the antiretroviral-therapy-naive study participants with viraemia carrying sensitive virus at the baseline. Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives.


Effects of roasting on composition of chili seed and storage stability of chili seed oil.
This work focused on how roasting changed the chemical components of chili (Capsicum annuum L.) seeds and how it affected the stability of chili seed oils during storage. The oils from chili seeds before and after roasting treatments were stored at 63 °C for 30 days and then analyzed. Results showed that roasting changed the main sugars compositions and amino acid compositions (total content decreased from 15.9 to 7.4%), which confirmed that it could form brown pigments and volatile flavor compounds in pepper seeds after roasting. Compared with oil from unroasted seeds, oils from roasted seeds had greater oxidative stability and maintained greater antioxidant capacity during storage. These effects were possibly due to the synergistic of the neo-formed products by Maillard reaction, vitamin E, and other bioactive components. This investigation showed that roasting treatment could be considered as an appropriate method for extending the storage stability of chili seed oils.


Effects of the parasitic botfly Philornis carinatus on nestling house wrens, Troglodytes aedon, in Costa Rica.
I studied the life cycle of a botfly (Diptera: Muscidae: Philornis carinatus) and examined the effects of botfly ectoparasitism on nestling house wrens (Passeriformes: Troglodytidae: Troglodytes aedon) during three years in Costa Rica. At three study sites, I found that nestlings were relatively unaffected by botflies, in contrast to all other studies of birds infected with philornid botflies. At Monteverde, the main study site, infected chicks grew slightly slower and had slightly shorter tarsi and wing chords than uninfected chicks, but both groups fledged at similar weights. Since weight at fledging is the only growth character associated with post-fledging survivorship, botfly infections likely cost wrens little in terms of fitness. At all sites, fledging success did not differ between infected and uninfected nests. Botfly infections were more prevalent at two lower elevation sites than at the high elevation Monteverde side. Infection prevalence increased during the nesting season at all study sites, which suggests a botfly life cycle in which adult population levels increase during the wren breeding season and then decline during a dormant period when wrens are not nesting. Finally, botflies may attack chicks throughout the period before fledging, but there is no indication they locate nests before hatching. In sum, botfly parasitism on wrens appears to be benign, perhaps because the study sites are at the edge of the botfly's range or because wrens are not a preferred host.


[A comparative survey of sex hormones levels between elderly men with chronic heart failure and normal elderly subjects].
To understand the sex hormone levels in elderly men with chronic heart failure and the relationship between sex hormone levels and heart function. One hundred male patients diagnosed chronic heart failure clinically aged from 60 to 87 were selected in this study. All patients' left ventricular ejection fraction were less than 0.45. Four hundred elderly healthy men were studied as control. Blood samples were collected in the morning and TT, FT, DHEAS, SHBG, E(2), LH, FSH were measured. The results were compared with the hormone levels of healthy men with the same mean age. (1) In elderly men with chronic heart failure, the level of DHEAS was decreased with age (P < 0.05). However, the levels of SHBG, LH, FSH were increased with age (P < 0.05, P < 0.01). (2) Compared with healthy men the levels of TT, FT, E(2) and DHEAS were decreased significantly (P < 0.01) and the level of SHBG was significantly increased (P < 0.01). (3) The level of FT was positively correlated with LVEF (r = 0.279, P = 0.034). The androgen levels in elderly male patients with chronic heart failure were decreased significantly and the level of FT was negatively correlated with degree of heart failure.


Review: Axon pathology in age-related neurodegenerative disorders.
'Dying back' axon degeneration is a prominent feature of many age-related neurodegenerative disorders and is widespread in normal ageing. Although the mechanisms of disease- and age-related losses may differ, both contribute to symptoms. Here, we review recent advances in understanding axon pathology in age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. In particular, we highlight the importance of axonal transport, autophagy, traumatic brain injury and mitochondrial quality control. We then place these disease mechanisms in the context of changes to axons and dendrites that occur during normal ageing. We discuss what makes ageing such an important risk factor for many neurodegenerative disorders and conclude that the processes of normal ageing and disease combine at the molecular, cellular or systems levels in a range of disorders to produce symptoms. Pathology identical to disease also occurs at the cellular level in most elderly individuals. Thus, normal ageing and age-related disease are inextricably linked and the term 'healthy ageing' downplays the important contributions of cellular pathology. For a full understanding of normal ageing or age-related disease we must study both processes.


Cultural adaptations to a family life skills program: implementation in rural appalachia.
Numerous parent education programs have been developed to provide parents with the skills and support necessary to effectively improve their parenting abilities. The Strengthening Families Program (SFP) employs a "family skills training" approach for parents and their children (ages 6 to 10). This study focuses on the implementation and outcomes of a culturally adapted SFP in southwestern Virginia, an area known for its Appalachian culture. Two groups were compared (those that received an adapted curricula and those that did not) on retention rates, parental outcomes, child outcomes, and program satisfaction. Retention rates were significantly improved for those participants in the adapted curricula group; however, parent and child outcomes were not affected. Statistically significant improvements for parents were found in effective discipline practices, family cohesion, family conflict, confidence in parenting, and punishment practices; and for both groups of children in increased child social skills and closeness to mothers between pre- and post-test times.


Evaluating a skin cancer education program for the Deaf community.
Skin cancer is the most common, preventable, and treatable cancer, so public education has been a priority. Unfortunately, for the Deaf community, most skin cancer information is difficult to access, so tailored approaches are needed. Participants (N=136) were randomly assigned to view either a skin cancer education video in American Sign Language (n=75) or an alternate video (n=61). All participants completed skin cancer knowledge questionnaires at baseline, immediately post-intervention, and 2-month post-intervention. Control group participants could then transfer to the experimental condition, using their 2-month follow-up data as their baseline. Participants who saw the skin cancer video gained significantly more knowledge than control participants, demonstrating the video's effectiveness in increasing skin cancer control knowledge. There was no difference between the original experimental group and the delayed intervention group on knowledge gains.


Surgical closure of patent ductus arteriosus in pre-term babies.
To present by illustration the surgical options in neonatal PDA closure with emphasis on clip application. Photo/video-documentation of surgical closure of PDA in a neonate by clip application coupled with free-hand drawings showing PDA closure by ligation and division. Review of 38 neonates undergoing surgical PDA closure in our institution between 1998 and 2006. Overall survival following surgery was 100%. There was one case of residual PDA and three postoperative complications - 2 cases of pneumothorax and one chylothorax. The outcome of surgical closure of PDA in neonates is very good with zero mortality in our series and only few postoperative complications.


[Evolution of surgical activity related to the female stress urinary incontinence (SUI) with regard to the ageing of the French female population].
One of the main factors associated with urinary incontinence of women is aging. The total female French population seems to grow for 10 years, with more and more women over 60 years. The authors wanted to assess the evolution of the surgical activity related to the treatment of the urinary incontinence with regard to the aging of the female French population. The number of surgical procedures for the treatment of stress urinary incontinence was obtained by querying the database of the Agence Technique de l'Information sur l'Hospitalisation (ATIH) for the period 2002-2013. The Catalogue Des Actes Médicaux (CDAM) and the Classification Commune des Actes Médicaux (CCAM) were used to extract the codes relating to surgery of the female urinary incontinence during this period. Demographics data were obtained from the website of the National Institute of Demographic studies (INED). The results were then compared. On the 2002-2010 period, the total female French population increased by 5%. In the class of age over 60 years, it increased by 12.7%. Support-related surgical activity continued to decrease until 2013 with 17.3% interventions less than in 2002. The evolution of surgical activity does not seem to follow the evolution of the ageing of the population, even if age is a risk factor essential for the female urinary incontinence. The improvement of risk factors (gynecological, obstetrical), over the past decade, could explain this evolution. 3.


Fungitoxicity of essential oils against dermatophytes.
Sixteen essential oils were screened in vitro for their fungitoxicity against the two dermatophytes Trichophyton rubrum and Microsporum gypseum. Five oils (from Artemisia nelagrica, Caesulia axillaris, Chenopodium ambrosioides, Cymbopogon citratus and Mentha arvensis) showed strong activity and were assessed for their fungitoxicity against eight other dermatophytes as well as against Aspergillus fumigatus and Cladosporium trichoides. These five essential oils by formulation of ointments were able to cure experimental ringworm in guinea pigs within 7 to 12 days. Artemisia oil was found to be the most effective essential oil.


How the quality of third parties' settlement solutions is affected by the relationship between negotiators.
Observers watched videotapes of people negotiating. In half of the videotapes, the negotiators had a negative relationship; in the other half, the negotiators had a positive relationship. Some observers believed that the relationship was a genuine reflection of how the parties felt about one another; others were told that the behavior of negotiators was strategic (i.e., used by parties to gain advantage). Following the tape, observers recommended a settlement. Observers' suggestions were most efficient when the negotiators' relationship was positive and genuine; observers proposed significantly worse solutions when negotiators' relationships were negative and genuine. The authors advise mediators to focus on the issues rather than the emotional tone and to avoid the correspondence bias when observing conflicts among parties with negative relationships.


Interventional radiology: the corner-stone of breast management.
There has been considerable progress in recent years in both diagnostic and interventional breast imaging. Percutaneous procedures improve multidisciplinary management and provide patients with better information. Biopsies allow precise and accurate diagnosis avoiding repeated examinations causing the patient anxiety and unnecessary surgical procedures. Preoperative marking guides surgery, thus limiting insufficient or excessive ablation. Tumors' destruction can sometimes replace surgery in older or frail women.


Helicobacter pylori infection prevalence: Is it different in diabetics and nondiabetics?
Helicobacter pylori (HP) infection plays a significant role in the development of gastrointestinal complications and has a significant role in systemic inflammation. It has some extragastrointestinal manifestations like endocrine diseases. In this study, we aimed to compare the prevalence of HP infection in diabetic and nondiabetic individuals. In this cross-sectional study, 218 nondiabetic and 211 diabetic patients referring to Shahid Beheshti Hospital of Qom between March 2013 and 2014 were studied. The patients were divided into two HP(+) and HP(-) groups based on serological immunoglobulin G antibody against HP and the association between diabetes, and HP infection was evaluated. Data were analyzed using independent t-tests, Chi-square, Fisher's exact and Mann-Whitney tests. The prevalence of HP seropositive was 65.9% versus 50.5% in diabetic and nondiabetics, respectively, and the difference was statistically significant (P = 0.001). This study showed a higher prevalence of HP infection in diabetic patients.


Evidence that a lineage of teleost-infecting blood flukes (Aporocotylidae) infects bivalves as intermediate hosts.
The family Aporocotylidae is recognized as having the widest intermediate host usage in the Digenea. Currently, intermediate host groups are clearly correlated with definitive host groups; all known life cycles of marine teleost-infecting aporocotylids involve polychaetes, those of freshwater teleost-infecting aporocotylids involve gastropods, and those of chondrichthyan-infecting aporocotylids involve bivalves. Here we report the life cycle for a marine elopomorph-infecting species, Elopicola bristowi Orélis-Ribeiro & Bullard in Orélis-Ribeiro, Halanych, Dang, Bakenhaster, Arias & Bullard, 2017, as infecting a bivalve, Anadara trapezia (Deshayes) (Arcidae), as the intermediate host in Moreton Bay, Queensland, Australia. The cercaria of E. bristowi has a prominent finfold, distinct anterior and posterior widenings of the oesophagus, a tail with symmetrical furcae with finfolds, and develops in elongate to oval sporocysts. We also report molecular data for an unmatched aporocotylid cercaria from another bivalve, Megapitaria squalida (G. B. Sowerby I) (Veneridae), from the Gulf of California, Mexico, and six unmatched cercariae from a gastropod, Posticobia brazieri (E. A. Smith) (Tateidae), from freshwater systems of south-east Queensland, Australia. Phylogenetic analyses demonstrate the presence of six strongly-supported lineages within the Aporocotylidae, including one of elopomorph-infecting genera, Elopicola Bullard, 2014 and Paracardicoloides Martin, 1974, now shown to use both gastropods and bivalves as intermediate hosts. Of a likely 14 aporocotylid species reported from bivalves, six are now genetically characterised. The cercarial morphology of these six species demonstrates a clear distinction between those that infect chondrichthyans and those that infect elopomorphs; chondrichthyan-infecting aporocotylids have cercariae with asymmetrical furcae that lack finfolds and develop in spherical sporocysts whereas those of elopomorph-infecting aporocotylids have symmetrical furcae with finfolds and develop in elongate sporocysts. This morphological correlation allows predictions of the host-based lineage to which the unsequenced species belong. The Aporocotylidae is proving exceptional in is propensity for major switches in intermediate host use, with the most parsimonious interpretation of intermediate host distribution implying a minimum of three host switches within the family.


Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP.
Fragile X Syndrome is the most common form of inherited mental retardation worldwide. A Fragile X mouse model, fmr1(tm1Cgr), with a disruption in the X-linked Fmr1 gene, has three substantial deficits observed in several strains: (1) sensitivity to audiogenic seizures (AGS), (2) tendency to spend significantly more time in the center of an open field, and (3) enlarged testes. Alterations in metabotropic glutamate receptor group I signaling were previously identified in the fmr1(tm1Cgr) mouse. In this study, we examined the effect of MPEP, an antagonist of the group I metabotropic glutamate receptor mGluR5, on audiogenic seizures and open field activity of fmr1(tm1Cgr) mice. Genetic analysis revealed synergistic reactions between fmr1(tm1Cgr) and inbred AGS alleles. In addition, AGS sensitivity due to the fmr1(tm1Cgr) allele was restricted during development. Examination of phenotypes combining mGluR5 inhibition and Fmr1 mutation indicated that absence of FMRP may affect mGluR5 signaling through indirect as well as direct pathways. All strains of fmr1(tm1Cgr) mice tested (FVB/NJ, C57BL/6J, and an F1 hybrid of the two) had a more excitable AGS pathway than wild-type, and consequently required more MPEP to achieve seizure suppression. At high doses of mGluR5 antagonists, a Fragile X specific tolerance (loss of drug activity) was observed. The tolerance effect could be overcome by a further increase in drug dose. In open field tests, MPEP reduced fmr1(tm1Cgr) center field behavior to one indistinguishable from wild-type. Therefore, mGluR5 antagonists were able to rescue two of the major phenotypes of the FX mouse. Modulation of mGluR5 signaling may allow amelioration of symptoms of Fragile X Syndrome.


Parietal neurons encoding spatial locations in craniotopic coordinates.
The receptive fields of visual neurons are known to be retinotopically arranged, and in awake animals they "move" with gaze, maintaining the same retinotopic location regardless of eye position. Here, we report the existence in the monkey parietal cortex of cells (called "real-position" cells) whose receptive field does not systematically move with gaze. These cells respond to the visual stimulation of the same spatial location regardless of eye position and therefore directly encode visual space in craniotopic instead of retinotopic coordinates.


Comparative transcriptomic analysis reveals genes related to the rapid accumulation of oleic acid in Camellia chekiangoleosa, an oil tea plant with early maturity and large fruit.
Camellia chekiangoleosa has a higher oleic acid content and a shorter reproductive cycle than typical oil tea plants. It was intensively sampled over six C. chekiangoleosa seed development stages. The content of fatty acids determined by GC showed that the accumulation of fatty acids gradually increased from the S1 to S5 stages, and the maximum concentration was reached in S5. Then, fatty acids declined slightly in S6. The main fatty acid component showed the same accumulation trend as the total fatty acids, except linolenic acid, which remained at a low level throughout seed developmental stages. Changes in the expression of fatty acid accumulation-related genes were monitored using second-generation and SMRT full-length transcriptome sequencing. Finally, 18.92 G accurate and reliable data were obtained. Differential expression analysis and weighted coexpression analysis revealed two "gene modules" significantly associated with oleic acid and linoleic acid contents, and the high expression of ENR, KAS I, and KAS II, which accumulate substrates for oleic acid synthesis, was thought to be responsible for the rapid accumulation of fatty acids in the early stage. The rapid increase in fatty acids in the second stage may be closely related to the synergy between the high expression of SAD and low expression of FAD2. In addition, many transcription factors, such as ERF, GRAS, GRF, MADS, MYB and WRKY, may be involved in the fatty acid synthesis. Our data provide a rich resource for further studies on the regulation of fatty acid synthesis in C. chekiangoleosa.


The safety of high-dose dexmedetomidine after cardiac surgery: a historical cohort study.
The off-label use of dexmedetomidine beyond the monograph-recommended maximum dose of 0.7 µg·kg-1·hr-1 is common in postoperative cardiac surgical units; however, limited data exist on the association of higher doses and adverse hemodynamic effects. We sought to compare the rate of hypotension or bradycardia in cardiac surgery patients receiving peak infusion doses below and above 0.7 µg·kg-1·hr-1 for any indication or duration. In this historical cohort study, we reviewed all patients who received dexmedetomidine infusion after cardiac surgery between June 2013 and July 2017 at a single centre. Regardless of the duration of exposure at the peak infusion dose, patients were categorized into high- or standard-dose groups using 0.7 µg·kg-1·hr-1 as the cutoff value. We compared rates of the primary composite outcome of hypotension or bradycardia, and secondary outcomes (i.e., arrhythmia and hyperglycemia) between groups using the two-proportion z test. Exploratory regression models were fitted to adjust for potential confounders. The median [interquartile range (IQR)] peak infusion dose was 1.0 [1.0-1.4] µg·kg-1·hr-1 in the high-dose group (N = 121) and 0.5 [0.4-0.7] µg·kg-1·hr-1 in the standard-dose group (N = 124). The rates of the primary composite outcome were 73% and 65%, respectively (absolute risk difference, 8%; 95% confidence interval, -3 to 20; P = 0.17). There was no significant difference in primary or secondary outcomes between groups. There was a high overall rate of hypotension or bradycardia in patients receiving dexmedetomidine after cardiac surgery; infusion rates below or above 0.7 µg·kg-1·hr-1 had similar rates of adverse hemodynamic events.


The androgenic effect on the fine structure on the Harderian gland in the male hamster.
A sexual dimorphism of the hamster Harderian gland at the ultrastructural level has been reported. The effect of testosterone on the fine structure of the gland from castrated male golden hamsters is reported here. Harderian glands from the following three groups of animals were examined at regular intervals up to 60 days after castration: (1) castrated; (2) castrated-sham-injected, receiving 0.1 ml sesame oil per day; (3) castrated-testosterone-injected, receiving 2 mg testosterone propionate in 0.1 ml sesame oil per day. In groups 1 and 2, clusters of cylindrical tubules, typical of the male gland, decreased in number and disappeared almost completely 2 wailed in these two groups throughout the remaining period of experiment. On the other hand, these changes were prevented in the group of castrated animals maintained on testosterone propionate. It is concluded that castration modified the ultrastructure of the male hamster Harderian gland toward the female type and that daily administration of testosterone propionate prevented this change.


Evaluation of sulfathiazole degradation by persulfate in Milli-Q water and in effluent of a sewage treatment plant.
The presence of antibiotics and their metabolites in natural waters has raised some concern among scientists around the world because it can lead to bacterial resistance and other unknown consequences to mankind and wildlife. Persulfate (PS)-driven oxidation is a new technology that has been used successfully to remediate contaminated sites, but its use to treat wastewater, especially sewage treatment plant (STP) effluent, is still scarce. This paper describes the effect of several persulfate activation methods for degrading sulfathiazole (STZ) in Milli-Q water and in STP effluent. Some parameters, such as pH, persulfate concentration, presence of Mn2+, Zn2+, Cu2+, Fe2+, and Fe3+, as well as copper and iron organic complexes, were studied in STZ degradation. Raising the pH from 5 to 9, as well as the persulfate concentration, resulted in increased STZ degradation. Among the transition metals evaluated, only Fe2+ and Cu2+ were able to activate persulfate molecules. Copper was a better activator than iron since its effect lasts longer. Citrate was the best ligand evaluated increasing Fe(II) activation capacity at pH 7. Hydroxylamine addition to Fe(II) on persulfate system extended the Fe(II) effect. The presence of bicarbonate or humic acid did not affect PS-driven degradation of STZ. Finally, the degradation of STZ in STP effluent promoted by PS-driven oxidation (25 °C) was as fast as in Milli-Q water, proving to be successful.


Wallerian degeneration in peripheral nerve disease.
This article first reviews the different classes of nerve injury. The temporal evolution of electrophysiologic changes occurring during Wallerian degeneration in humans is then described, followed by a description of sequential structural changes and cellular responses that occur after nerve transection. The final section focuses on the basis for resurgent research interest in Wallerian degeneration and the different research approaches being taken to answer basic science and clinical questions.


Cloudwater studies at a high elevation site in the Vosges Mountains (France).
Cloud and rainwater samples have been collected at a high elevation site in the Vosges Mountains. An automated collection system has been used to collect bulk cloudwater and small cloudwater droplets. Bulk cloudwater concentrations were up to 10 times more concentrated than rainwater concentrations. Small clouddroplets showed generally higher concentrations than bulk cloudwater. Nevertheless, the enrichment factors depend on the compounds under study and appear to be related to the composition of the cloud condensation nuclei forming small or large clouddroplets. Principal component analysis and factor analysis were applied to the collected datasets and confirmed the influence of the cloud condensation nuclei on the composition difference between small and large cloudwater droplets.


Tetrocarcins, novel antitumor antibiotics. I. Producing organism, fermentation and antimicrobial activity.
A novel antitumor antibiotic complex has been obtained from the culture broth of Actinomycete strain DO-11 (KY11091) isolated from a soil sample collected in Sendai, Miyagi, Japan. On the taxonomic studies the producing organism is described as Micromonospora chalcea KY11091. For the production of the antibiotics, soluble starch served as a good carbon source and yeast extract was the best nitrogen source tested. The antibiotic complex designated as tetrocarcins is active against Gram-positive bacteria, but is not active against Gram-negative bacteria. Tetrocarcin A showed bacteriocidal activity against Bacillus subtilis.


Downregulation of miR-122 by porcine reproductive and respiratory syndrome virus promotes viral replication by targeting SOCS3.
MicroRNAs are small non-coding RNA that regulate host anti-viral immune response. In this study, we used high-throughput sequencing to identify miRNAs that were differentially expressed upon PRRSV infection in porcine alveolar macrophages. We observed that the expression level of miR-122 was decreased upon PRRSV infection. Over-expression of miR-122 remarkably suppressed PRRSV replication, while blockage of endogenous miR-122 enhanced PRRSV replication. Moreover, over-expression of miR-122 reduced the protein level of porcine suppressor of cytokine signaling 3 (SOCS3), a negative regulator of JAK-STAT signaling, resulting in enhanced production of type Ⅰ IFN. Further analysis revealed that miR-122 decreased the expression of SOCS3 at the post-transcription level by targeting the 3' UTR region of SOCS3 mRNA. In conclusion, this study demonstrates that the expression of miR-122 was reduced during PRRSV infection. miR-122 impaired PRRSV replication by promoting the production of type I interferon. Our study may provide new insights into understanding PRRSV immune evasion mechanisms.


Identification and localization of hookworm platelet inhibitor in Ancylostoma ceylanicum.
Ancylostoma ceylanicum is a zoonotic hookworm, which mainly causes iron deficiency anemia (IDA) in humans and animals. Hookworm platelet inhibitor (HPI) has been isolated from adult Ancylostoma caninum and linked to the pathogenesis of hookworm associated intestinal hemorrhage and IDA. However, there is no available data about HPI from A. ceylanicum. To study the molecular characteristics of A. ceylanicum HPI (Ace-HPI), its corresponding cDNA was amplified from adult A. ceylanicum mRNA using the primers designed based on the Ac-HPI gene sequence, and its sequence homology and phylogenetic relationship were analyzed. The differential expression of Ace-hpi mRNA in the adult and third larval (L3) stages was compared using the quantitative real-time PCR. Ace-HPI reactivity and tissue localization were studied by Western blot and immunofluorescence, respectively. Platelet aggregation activity was monitored in a 96-well microplate reader. The results showed that the Ace-HPI encoding gene was 603 bp in length. Ace-HPI showed 91% homology to Ac-HPI, was closely related to Ac-ASP3, and belonged to the CAP superfamily. Ace-hpi transcripts were most abundant in the adult stage, followed by serum-stimulated infective larvae (ssL3), and finally in L3 stage, with a significant difference. Escherichia coli-expressed recombinant protein had good reactivity with the positive serum of A. ceylanicum-infected dogs. Immunolocalization indicated that Ace-HPI was located in the esophagus and cephalic glands of the adult. As well as, recombinant Ace-HPI inhibited the platelet aggregation in-vitro. HPI overexpression, anatomical location in adults, antigenicity and its in-vitro activity indicate its possible role in adult worm blood-feeding and as a valuable target for hookworm vaccine and drug development.


Risk-based screening for second primary extrapulmonary malignancies in stage I lung cancer patients: A study based on SEER database.
We conducted this study to identify the risk for second primary malignancy (SPM), especially for second primary extrapulmonary malignancy (SPEM), in resected stage I lung cancer patients. Resected stage I lung cancer patients were retrospectively enrolled from the SEER database (2008-2017). Standardized incidence ratio (SIR) was used to evaluate the relative risk of SPM of patients as compared to general population. Competing risk model was utilized to identify the risk factors for SPEM of increased risk (rSPEM). A simplified nomogram based on the factors was developed to stratify patients at different risks of rSPEM. A total of 14,495 patients were enrolled, and 1779 (12.27%) patients developed SPM during follow-up, of which 896 (50.37%) were SPEM. Enrolled patients had higher risk of SPM than general population (SIR: 1.92, 95% CI: 1.83 - 2.01). The yearly morbidity of SPM was about 3% - 4% over time. The three most frequent SPEM were prostate cancer, breast cancer, and urinary bladder cancer. The competing-risk multivariable analysis showed that increasing age, male, and white race were independent risk factors for rSPEM. The simplified nomogram showed favorable performance in stratifying patients at different risks of rSPEM (P < 0.001). The risk of SPM in stage I lung cancer patients was high. Risk factors for rSPEM were identified and the corresponding simplified nomogram based on the risk factors could discriminate patients at different risks well. The nomogram might help physicians to make more appropriate screening strategy for the SPEM.


Synthesis of co-pyrolyzed biochar using red mud and peanut shell for removing phosphate from pickling wastewater: Performance and mechanism.
Iron (Fe)/iron oxide-modified biochar has practicable adsorption capability for phosphorus (P), but it is expensive. In this study, we synthesized novel low-cost and eco-friendly adsorbents co-pyrolyzed biochars using Fe-rich red mud (RM) and peanut shell (PS) wastes via a one-step pyrolysis process for removing P from pickling wastewater. The preparation conditions (heating rate, pyrolysis temperature, and feedstock ratio) and P adsorption behaviors were systematically investigated. In addition, a series of characterization and approximate site energy distribution (ASED) analyses were conducted to understand the P adsorption mechanisms. The magnetic biochar (BR7P3) with m (RM):m (PS) of 7:3 prepared at 900°C and 10 °C/min had a high surface area (164.43 m2/g) and different abundant ions (including Fe3+, and Al3+). In addition, BR7P3 exhibited the best P removal capability (142.6 mg/g). The Fe2O3 from RM was successfully reduced to Fe0, which was easily oxidized as Fe3+ to precipitate with H2PO4-. The electrostatic effect, Fe-O-P bonding, and surface precipitation were the main mechanisms of P removal. ASED analyses revealed that high distribution frequency and solution temperature led to a high P adsorption rate of the adsorbent. Therefore, this study provides new insight into the waste-to-wealth strategy by transforming PS and RM into mineral-biomass biochar with excellent P adsorption capability and environmental adaptability.


The enkephalin-containing cell: strategies for polypeptide synthesis and secretion throughout the neuroendocrine system.
1. Enkephalinergic cells are found throughout the diffuse neuroendocrine system, in the adrenal medulla, brain, spinal cord, peripheral and enteric nervous systems, and endocrine pancreas. 2. In each of these diverse cell types, the enkephalin phenotype is (i) established during development, (ii) modified by the particular environment in which the cell is located, and (iii) maintained by ongoing biosynthesis at a rate consistent with loss of enkephalins from the cell during periods of secretion. 3. Enkephalin expression and biosynthesis have been studied in several neuroendocrine cell types and tumor cell lines. Transcriptional, translational, and posttranslational factors can play a role at all three stages (establishment, modification, and maintenance) in the regulation of enkephalin expression during the lifetime of the cell. 4. Cyclic nucleotides, glucocorticoids, and calcium may all act to control the overall level of enkephalin biosynthesis pretranslationally, while regulation of posttranslational processing of proenkephalin seems to be important in determining the pattern of proenkephalin-derived opiate peptides produced in a given tissue. 5. The themes (and variations) of cell regulation that apply to enkephalin expression may be similar for other bioactive peptides produced in neural and endocrine tissues.


Early detection and treatment: social worker and pediatricians in private practice.
A social worker in the private group practice of pediatricians provides multiple and varied services to children and families. Findings from the first six months of a demonstration project suggest that service is rapidly provided and is utilized by referred patients. Professional issues of practice and education are identified and discussed.


Carboxyl groups near the active site zinc contribute to catalysis in yeast alcohol dehydrogenase.
The importance of carboxyl groups near the active site zinc for the catalytic function of alcohol dehydrogenase I from Saccharomyces cerevisiae was examined by directed mutagenesis and steady state kinetics. Asp-49 was changed to asparagine and Glu-68 to glutamine (residue numbering as for horse liver enzyme). The catalytic efficiencies (V/Km) for ethanol oxidation and acetaldehyde reduction were decreased by factors of 1000 with the Asn-49 mutant and 100 with the Gln-68 enzyme. For the Asn-49 mutant, dissociation constants for coenzymes increased 7-fold, and Michaelis and inhibition constants for substrates and substrate analogs increased by factors of 20-50. The turnover numbers were reduced 50-fold for ethanol oxidation and 15-fold for acetaldehyde reduction. Product and dead-end inhibition studies and kinetic isotope effects showed that the mechanism with NAD+ and ethanol was rapid equilibrium random, in contrast to the ordered mechanism of wild-type enzyme. Alcohol dehydrogenase I and the Asn-49 mutant had similar CD spectra and 2 zinc atoms/subunit, but slightly different UV absorption and fluorescence spectra. The Gln-68 mutant resembled the wild-type enzyme in most kinetic constants, but the turnover number for ethanol oxidation decreased 35-fold, and Kd for NAD+ and Km for acetaldehyde increased by factors of 4 and 50, respectively. The pK values for V1 and V1/Km for ethanol oxidation were shifted from 7.7 (wild-type) to 6.8 in the Gln-68 and 6.2 in the Asn-49 mutant. The altered electrostatic environment near the active site zinc apparently decreases activities by hindering isomerizations of enzyme-substrate complexes.


Central nervous system distribution kinetics of indinavir in rats.
The central nervous system (CNS) distribution kinetics of indinavir were extensively evaluated using a combinational in-vivo model comprising the integration plot method (a single-passage approach) and neuropharmacokinetic method (a multiple-passage approach). A 5 mg kg(-1) dose of indinavir was administered intravenously to rats. Blood and cerebrospinal fluid (CSF) samples and whole brain were collected from the animals at specified time points and the drug concentration in each sample was determined using a high-performance liquid chromatography method. For the neuropharmacokinetic study, the simultaneous plasma, CSF and brain concentrations were fitted to an integrated model, which resulted in the estimation of the influx (K(in)) and efflux (K(out)) rate constants of the drug to/from CSF and brain parenchyma. The integration plot method involved plotting the brain-plasma or CSF-plasma concentration ratios (K(p, app)) against AUC(0-->t)/C(p(t)), and estimating the uptake clearance of the drug by brain/CSF from the slope of the initial linear portion of the plot. The K(in) and K(out) values of the drug to/from CSF were estimated to be 2.42 x 10(-2) and 13.26 x 10(-2)min(-1), respectively, and the corresponding values for brain parenchyma were 1.02 x 10(-2) and 1.32 x 10(-2) min(-1), respectively. The uptake clearances of indinavir by CSF and brain parenchyma were 8.89 and 8.38microL min(-1)g(-1), respectively. The permeability surface area products of the drug for the blood-brain barrier and blood-CSF barrier were estimated as 1.05 x 10(-2) and 2.45 x 10(-2) mLmin(-1)g(-1), respectively. The estimated kinetic parameters indicated limited CNS entry of the drug because of the limited blood-brain barrier permeability and the efficient drug efflux from CNS, particularly from CSF.


PyLasso: a PyMOL plugin to identify lassos.
Entanglement in macromolecules is an important phenomenon and a subject of multidisciplinary research. As recently discovered, around 4% of proteins form new entangled motifs, called lassos. Here we present the PyLasso-a PyMOL plugin to identify and analyse properties of lassos in proteins and other (bio)polymers, as well as in other biological, physical and mathematical systems. The PyLasso is a useful tool for all researchers working on modeling of macromolecules, structure prediction, properties of polymers, entanglement in fluids and fields, etc. The PyLasso and tutorial videos are available at http://pylasso.cent.uw.edu.pl. firstname.lastname@example.com.


Low pressure ion chromatography with a low cost paired emitter-detector diode based detector for the determination of alkaline earth metals in water samples.
The use of a low pressure ion chromatograph based upon short (25 mm x 4.6 mm) surfactant coated monolithic columns and a low cost paired emitter-detector diode (PEDD) based detector, for the determination of alkaline earth metals in aqueous matrices is presented. The system was applied to the separation of magnesium, calcium, strontium and barium in less than 7min using a 0.15M KCl mobile phase at pH 3, with post-column reaction detection at 570 nm using o-cresolphthalein complexone. A comparison of the performance of the PEDD detector with a standard laboratory absorbance detector is shown, with limits of detection for magnesium and calcium using the low cost PEDD detector equal to 0.16 and 0.23 mg L(-1), respectively. Finally, the developed system was used for the determination of calcium and magnesium in a commercial spring water sample.


Gelatin interpenetration in poly N-isopropylacrylamide network reduces the compressive modulus of the scaffold: A property employed to mimic hepatic matrix stiffness.
The progression of liver disease from normal to cirrhotic state is characterized by modulation of the stiffness of the extracellular matrix (ECM). Mimicking this modulation in vitro scaffold could provide a better insight into hepatic cell behavior. In this study, interpenetrating poly(N-isopropylacrylamide-co-gelatin) cryogels were synthesized in 48 different compositions to yield scaffolds of different properties. It was observed that a high concentration of N-isopropylacrylamide (NIPAAm) leads to the formation of small pores while gelatin interpenetration on poly-NIPAAm framework renders porous structure. Swelling properties and porosity of the gels decreased with an increase in NIPAAm concentration owing to the increased compactness of the gels. Gelatin interpenetration relaxed the gels and enhanced these properties. An increase in gelatin concentration led to a reduction in compressive moduli indicating that gelatin interpenetration in the poly-NIPAAm network softens the cryogel. With the increase in NIPAAm concentration, the effect of gelatin interpenetration in reducing the compressive moduli expanded. The cytocompatibility studies indicated that the gels are cell-adherent and compatible with HepG2. Furthermore, biochemical and real-time polymerase chain reaction studies revealed that HepG2 and Huh-7 cells cultured on scaffolds mimicking the ECM stiffness of normal liver (1.5-2.5 kPa) exhibited optimum liver-specific functionalities. Increasing the stiffness to fibrotic (4-9 kPa) and cirrhotic (10-20 kPa) ECM decreases the functionality.


Associations Between Relationship Power and Pre-Exposure Prophylaxis (PrEP) Use Among Men Who Have Sex With Men.
Few studies have attempted to understand relationship-level factors impacting PrEP utilization among men who have sex with men (MSM). This study examined associations between relationship power and PrEP use among 826 MSM participating in a cross-sectional, Internet-based survey. The results of our analysis indicate that decision-making dominance was positively associated with PrEP use among MSM, but the association between relationship control/overall relationship power and PrEP use was inconclusive. Furthermore, when examining specific types of decision-making dominance, equal and greater dominance compared to one's partner regarding types of sexual activity engaged in, as well as dominance more generally, were positively associated with PrEP use. However, the relationships between decision-making dominance related to condom use/sexual initiation and PrEP use were inconclusive. This study suggests that the promotion of egalitarian relationships-as well as other relationship-level determinants-should be an essential component of biobehavioral interventions targeting this population.


A new species of Metacyclops from a hyporheic habitat in North Vietnam (Crustacea, Copepoda, Cyclopidae).
A new species of Metacyclops is described from hyporheic waters and small rock depression with leaf litter in North Vietnam, the Tam Đao Mountains). Metacyclops amicitiae sp. n. can be distinguished from its congeners by the unique combination of the following characters: 12-segmented antennule, distal segment of P4 endopodite bearing a single apical spine, and the surface ornamentation of the intercoxal sclerites in P1-P4 (pilose on the distal margin of P1-P4 and spinulose on the caudal surface of P4). The latter character separates the new Metacyclops from its closest relative, Metacyclops ryukyuensis, known only from the Ryukyu Islands (Ishigaki). The genus Metacyclops with the new species described herein is also for the first time recorded from Vietnam. An identification key is provided to the south and east Asian species of the genus.


Primary structure of human alpha 2-macroglobulin. III. Primary structure of three large disulfide-bridged CNBr fragments, located in the COOH-terminal part of alpha 2-macroglobulin and accounting for 301 residues.
The amino acid sequences have been determined for three CNBr fragments of human alpha 2-macroglobulin which form a disulfide-bridged Mr = 40,000 fragment set. The fragments are located in the COOH-terminal part of alpha 2-macroglobulin (CB18, residues 776-936; CB23, residues 1292-1355; and CB26, residues 1376-1451). CB18 contains one glucosamine-based carbohydrate group attached to Asn-71 and two internal disulfide bridges (Cys-23 bound to Cys-51 and Cys-49 bound to Cys-85, respectively). Cys-123 is disulfide bridged to Cys-7 of CB23. Cys-38 of CB23 is disulfide bridged to Cys-69 of CB26. CB26, which contains one glucosamine-based carbohydrate group attached to Asn-26, is the COOH-terminal CNBr fragment. CB18, CB23, and CB26 account for 301 of the 1451 residues of the subunit of alpha 2-macroglobulin.


Parenteral nutrition and oxidant stress in the newborn: A narrative review.
There is strong evidence that oxidant molecules from various sources contaminate solutions of parenteral nutrition following interactions between the mixture of nutrients and some of the environmental conditions encountered in clinical practice. The continuous infusion of these organic and nonorganic peroxides provided us with a unique opportunity to study in cells, in vascular and animal models, the mechanisms involved in the deleterious reactions of oxidation in premature infants. Potential clinical impacts of peroxides infused with TPN include: a redox imbalance, vasoactive responses, thrombosis of intravenous catheters, TPN-related hepatobiliary complications, bronchopulmonary dysplasia and mortality. This is a narrative review of published data.


Paresthesia in dentistry: The ignored neurotoxicity of local anesthetics.
Local anesthetics are frequently used by dentists to relieve localized discomfort of the patient and improve treatment conditions. The risk of paresthesia after local anesthesia is frequently encountered in dental clinics. The neurotoxicity of local anesthetics is a disregarded factor in paresthesia. The review summarizes the types of common local anesthetics, incidence and influencing factors of paresthesia after local anesthesia, and systematically describes the neurotoxicity mechanisms of dental local anesthetic. Innovative strategies may be developed to lessen the neurotoxicity and prevent paresthesia following local anesthesia with the support of a substantial understanding of paresthesia and neurotoxicity.


Didanosine extended-release matrix tablets: optimization of formulation variables using statistical experimental design.
Statistical experimental design was applied to evaluate the influence of some process and formulation variables and possible interactions among such variables, on didanosine release from directly-compressed matrix tablets based on blends of two insoluble polymers, Eudragit RS-PM and Ethocel 100, with the final goal of drug release behavior optimization. The considered responses were the percent of drug released at three determined times, the dissolution efficiency at 6 h and the time to dissolve 10% of drug. Four independent variables were considered: tablet compression force, ratio between the polymers and their particle size, and drug content. The preliminary screening step, carried out by means of a 12-run asymmetric screening matrix according to a D-optimal design strategy, allowed evaluation of the effects of different levels of each variable. The drug content and the polymers ratio had the most important effect on drug release, which, moreover, was favored by greater polymers particle size; on the contrary the compression force did not have a significant effect. The Doehlert design was then applied for a response-surface study, in order to study in depth the effects of the most important variables. The desirability function was used to simultaneously optimize the five considered responses, each having a different target. This procedure allowed selection, in the studied experimental domain, of the best formulation conditions to optimize drug release rate. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The results demonstrated the reliability of the model in the preparation of extended-release matrix tablets with predictable drug release profiles.


Optimising the combination of thermostabilising mutations in the neurotensin receptor for structure determination.
Conformational thermostabilisation of G protein-coupled receptors is a successful approach for their structure determination. We have recently determined the structure of a thermostabilised neurotensin receptor NTS1 in complex with its peptide agonist and here we describe the strategy for the identification and combination of the 6 thermostabilising mutations essential for crystallisation. First, thermostability assays were performed on a panel of 340 detergent-solubilised Ala/Leu NTS1 mutants and the best 16 thermostabilising mutations were identified. These mutations were combined pair-wise in nearly all combinations (119 out of a possible 120 combinations) and each mutant was expressed and its thermostability was experimentally determined. A theoretical stability score was calculated from the sum of the stabilities measured for each double mutant and applied to develop 24 triple mutants, which in turn led to the construction of 14 quadruple mutants. Use of the thermostability data for the double mutants to predict further mutant combinations resulted in a greater percentage of the triple and quadruple mutants showing improved thermostability than if only the thermostability data for the single mutations was considered. The best quadruple mutant (NTS1-Nag36k) was further improved by including an additional 2 mutations (resulting in NTS1-GW5) that were identified from a complete Ala/Leu scan of Nag36k by testing the thermostability of the mutants in situ in whole bacteria. NTS1-GW5 had excellent stability in short chain detergents and could be readily purified as a homogenous sample that ultimately allowed crystallisation and structure determination.


A procedure for selecting mammalian cells with an impairment in oxidative phosphorylation.
The mitochondrial encephalomyopathies in man are characterized by heterogeneous defects leading to an impairment in the pathway of aerobic energy production. As a means of investigating the molecular and genetic mechanisms underlying these disorders we have developed a procedure for selecting mammalian cell lines with features resembling the human pathological phenotypes. The principle of the selection is the use of a fluorescent amphiphilic dye, 2,4-(dimethylamino)-1-styrylmethylpyridiniumiodine, a cation showing two main features. Firstly, it is accumulated by mitochondria to an extent correlated with the magnitude of the electrochemical gradient of protons across the mitochondrial inner membrane. Secondly, upon irradiation with UV light, it gives rise to formation of free radicals, which inflict damage to the cell. Mutant cells with an impairment in oxidative phosphorylation will have more chance to survive than wild type cells. The selection procedure was applied to a stock of mutagenized Chinese hamster ovary cells. After subcloning of the cells which survived the selection procedure, twenty-six independent clones were isolated. Eighteen of the clones had a partial deficiency of cytochrome c oxidase ranging from 30 to 60% of the activity in control cells. The properties of two of the clones are described. One clone has been cultured under non-selective conditions for at least 12 months with retention of the partial deficiency of cytochrome c oxidase.


Reactivation of sarcoidosis during interferon therapy.
The exacerbation of a co-existing autoimmune disease is often a concern for physicians who use immunomodulating agents for the treatment of a concomitant process. As physicians begin to treat chronic hepatitis C more often and more aggressively, this potential problem with occur more frequently. Herein we reported a case of reactivation of sarcoidosis occurring during the treatment of chronic hepatitis C, and we present a literature review of other centers' experiences with this problem. Depending upon the severity of the exacerbation and the type of organ involvement, reactivation of sarcoidosis may require discontinuation of the interferon therapy, with or without the use of additional steroids. The majority of patients, however, do not require the use of steroids. Interestingly, continuation of the interferon therapy in the presence of a mild-to-moderate exacerbation of sarcoidosis may be safe in a minority of patients with noncritical organ involvement.


Proteome stability analysis of snap frozen, RNAlater preserved, and formalin-fixed paraffin-embedded human colon mucosal biopsies.
Large repositories of well characterized RNAlater preserved samples and formalin-fixed, paraffin-embedded samples have been generated worldwide. However, the impact on the proteome of the preservation methods remain poorly described. Therefore, we analyzed the impact on the proteome of preserving samples in RNAlater, and by formalin-fixation, paraffin-embedding on human soft tissue, using directly frozen samples as a control ("Comparing the proteome of snap frozen, RNAlater preserved, and formalin-fixed paraffin-embedded human tissue samples" [1]). We here report the data from the analysis. The comparative analysis was performed on 24 colon mucosa biopsies, extracted from the sigmoideum of two gastroenterologically healthy participants for the purpose of this study. A set of biopsies were additionally stored for 30 min at room temperature prior to formalin-fixation. The samples were analyzed by high throughput gel free quantitative proteomics. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PRIDE: PXD002029.


Intrahippocampal injections of ibotenic acid provide histological evidence for a neurotoxic mechanism different from kainic acid.
Stereotaxic injections of ibotenic acid (IBO) and kainic acid (KA) into either the dorsal hippocampus or the lateral cerebroventricle were performed in order to determine the relative potencies of the drugs and the vulnerability of different hippocampal cell types to their neurotoxic action, IBO was found to be approximately five times less potent than KA in causing degeneration of hippocampal neuronal cell bodies. Unlike KA (0.5 and 1.0 microgram), IBO (5.0 micrograms) caused few signs of intrahippocampal bleeding or necrosis of non-neuronal elements. Pyramidal cells of the CA3 and CA4 regions were the most sensitive and dentate granule cells the least sensitive to KA. In contrast, IBO cused degeneration of granule cells and CA3/CA4 pyramids to an equal extent.


Cell mediated and antibody immune response to inactivated hepatitis A vaccine.
The humoral and cellular immune response to inactivated hepatitis A vaccine was investigated dynamically in a time elapse study over 1 year. Fourty-five healthy volunteers, seronegative for anti-HAV, were vaccinated with 1440 enzyme-linked immunosorbent assay units (EU) of formalin-inactivated hepatitis A virus following a 0--6-month schedule. Serum anti-HAV levels and HAV-specific proliferation of peripheral blood mononuclear cells were measured at several time points over a 26- and 28-week period after the first and second injection, respectively. Distinct B and T cell responses were determined within 14 days after primary vaccination. The booster vaccination-induced immediate peak levels for the humoral (anti-HAV GMC=5376mIU/ml) as well as the cellular (median Deltacpm=14173cpm) response.


Recombinant human bone morphogenetic protein-7 and bone marrow as a substitute for bone graft in reconstruction defect of rabbit mandible.
To obtain information on the feasibility of employing recombinant human bone morphogenetic protein-7 (rhBMP-7), mixed with bone marrow as a substitute for autologous bone graft. We carried out the study in the University Clinic Center, Sarajevo, Bosnia and Herzegovina, from February 2002 to January 2004. Six New Zealand rabbits underwent hemiresection of the mandible. We placed rhBMP-7 in a concentration of 100 micrograms and collagen (ACS) as carrier mixed with bone marrow in the defects in 3 animals. In another group of 3, we restored the defect by placement of autologous bone graft harvested from the iliac crest. We evaluated the results by the activity of the alkaline phosphatase enzyme (ALP), CT assessment with bone mineral density (BMD) analysis, and clinical and histologic examinations. The ALP activity was significantly higher after 14 days, in the rhBMP7/ACS sites than the bone graft sites (30th day). Mean BMD of tissue induced by rhBMP-7/ACS on the 30th day was 510 mg/cm3 in caudal, and 553 mg/cm3 in sagittal plane, and bone graft tissue was 510 mg/cm3 in caudal and 530 mg/cm3 in sagittal plane. Clinical inspection and histologic examination on the 60th day showed complete bridged defects with abundant woven bone in 2 of 3 rhBMP-7/ACS sites (67%), and no incorporation of the autologous bone graft into the other groups treated sites. The rhBMP-7/ACS mixed with bone marrow was very effective in establishing complete bone regeneration into the defects, indicating that it could be an adequate alternative for autologous bone transplantation.


Ocular hypotensive action of labetalol.
Labetalol has a unique and profound effect on the IOP of rabbits, in contrast to pure beta-adrenergic blockers which have little or no effect in this animal. Its action cannot be satisfactorily explained by simple alpha and beta-adrenergic blocking activity. In the concentrations used, it failed to block the action of a beta-adrenergic agonist (isoproterenol), the action of an alpha-adrenegic agonist (norepinephrine), and its own hypotensive action was neither blocked nor potentiated by the alpha-adrenergic blocker phenoxybenzamine. However, the beta blocker, timolol, did reduce the action of labetalol. These observations and the reduced response to labetalol after cervical sympathectomy, suggest that labetalol's ocular hypotensive effect may occur through some mechanism other than alpha or beta blockade.


Hemolytic activity of new linear surfactin analogs in relation to their physico-chemical properties.
New linear analogs of surfactin have been synthesized. Their physico-chemical parameters were determined. The results indicate that these linear products show surface activities although they are lowered compared to those of cyclic compounds. The hemolytic activities have also been assayed. In contrast with cyclic surfactins, no significant hemolysis occurs for the linear products in the range of concentrations tested. Moreover, a protective effect against Triton X-100 induced hemolysis has been highlighted for linear surfactins. The concentration at which this protective effect happens is correlated directly to the CMC, and inversely to the acyl chain length of the product. In a hypotonic medium, analogs having a long acyl chain tend to increase the hemolysis, meanwhile the product with the shortest chain tends to decrease it.


Tumors of the central nervous system.
Neoplasia of the central nervous system (CNS) can be divided into two main categories: nonpituitary CNS neoplasia and pituitary adenomas. Nonpituitary CNS neoplasias are generally compressive in nature, although some are also invasive. The majority of reported CNS tumors are secondary with only a few originating from nervous tissue. Pituitary adenomas predominantly occur in the pars intermedia of the older horse. Clinical signs, diagnostic testing, and possible treatments are discussed.


Quantification of succinic acid levels, linked to succinate dehydrogenase (SDH) dysfunctions, by an automated and fully validated liquid chromatography tandem mass spectrometry method suitable for multi-matrix applications.
The hallmarks of cancer include metabolism with deregulating cellular energetics. Dysfunctions in succinate dehydrogenase (SDH) metabolic enzyme activity, leading to an abnormal accumulation of succinic acid has been described in solid tumors but also in inflammation and ischemia reperfusion injury. Succinic acid is a potential biomarker of SDH related pathologies for diagnostic, evaluation of treatment response and follow-up of the disease. We developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method allowing a rapid, accurate and precise quantification of succinic acid levels in clinical (serum, urine) and preclinical (cellular pellets, supernatants) samples. 13C4 succinic acid disodium salt was used as internal standard and added to samples before a solid phase extraction (SPE) on Phenomenex STRATATM XL-A (200 mg - 3 mL) 33 µm cartridges. This method is automated by a Freedom EVO® platform from TECAN and succinic acid is separated on a C18 column combined to a Xevo® TQ-S micro Waters mass spectrometer with electrospray ionization (ESI) source. This biomedical analysis allows standard curves to be linear over the range 1.0-135.5 µM with r2 values > 0.999 and low matrix effects (<9.1 %). This method, which is validated according updated European Medicine Agency (EMA) guidelines, is accurate between-run (<11.0 %) and within-run (<7.8 %), precise between-run (<14.4 CV %) and within-run (<3.7 CV %), and is suitable for clinical and preclinical applications.


Systemic inflammation after drug-eluting stent placement.
Systemic inflammation after coronary intervention identifies patients at increased risk of subsequent cardiac events. Cardiac events are less frequent after use of drug eluting stents (DES) compared with bare metal stents (BMS). Thus, we sought to determine whether attenuation of the systemic inflammatory response was contributing to the improved outcomes. A prospective registry was initiated in late 2003. Peripheral venous blood samples from 75 patients undergoing percutaneous coronary intervention (PCI) were obtained before PCI, and both 1 hour and 24 hours after stenting. The concentrations of C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL1-Ra) were determined by ELISA. Eleven patients were excluded from the analysis because they had both DES and BMS. Patients treated with BMS (n=29) compared with DES (n=34) had a higher incidence of marker-positive acute coronary syndromes (40% vs. 17%, p=0.06), vein graft PCI (p=0.02) and a larger final balloon diameter (p=0.04). Consistent with the lower baseline clinical risk, pre-PCI concentrations of cytokines were lower in the DES group (p=0.04 for IL-6 and p=0.08 for CRP). Comparable and significant increases in CRP, IL-6 and IL1-Ra were evident 24 hours after PCI in patients treated with either DES or BMS. After controlling for baseline levels of CRP, there remained a similar and robust (300%) relative increase in CRP for both DES and BMS patients. The inflammatory response to PCI appears similar in those treated with DES and BMS. Accordingly, the reduction in restenosis after DES is likely not mediated by attenuation of the systemic markers CRP, IL-1Ra, or IL-6.


The effect of drug-induced thrombocytopenia on direct-current transcatheter electrocoagulation.
Direct-current transcatheter electrocoagulation in vitro produced substantial clots in thrombocytopenic blood in dogs. The splenic artery was occluded in 3 dogs following ristocetin-induced thrombocytopenia. This procedure may produce effective vessel occlusion in patients with platelet-poor blood.


Impaired pulmonary function mediates inattention in young adults born extremely preterm.
To test whether poor childhood pulmonary function explains the relationship between extremely preterm (EP) birth and attention-deficit/hyperactivity disorder (ADHD) symptoms in young adulthood. EPICure birth cohort participants include children born <26 weeks' gestation in the United Kingdom and Ireland in 1995 and their term-born classmates. Predictor was EP birth. Outcomes were inattention/hyperactivity subscale z-scores at 19 years. Forced expiratory volume (FEV1) z-scores in childhood and young adulthood were mediators. We used recursive path analysis to determine the direct effect of EP birth on inattention/hyperactivity and its indirect effect through pulmonary function. Ninety EP and 47 term-born participants had pulmonary function testing at 11 and 19 years. Inattention z-scores were higher in the EP group (mean difference 0.55 [95% CI 0.11, 0.99]) but not hyperactivity. Compared to term-born peers, EP participants had lower FEV1 z-scores at 11 (mean difference-1.35 [95% CI -1.72, -0.98]) and 19 (mean difference-1.29 [95% CI -1.65, -0.92]). Path models revealed that childhood pulmonary function explained the relationship between EP birth and inattention. Extremely preterm young adults have increased risk for inattention compared to term-born peers. Poor pulmonary function appears to underlie this risk. The mechanisms responsible remain unclear and warrant further study.


How I do it: re-do surgery for recurrent trigeminal neuralgia.
When trigeminal neuralgia recurs after microvascular decompression surgery, re-operation may be indicated if trigeminal nerve compression remains. However, surgery for recurrent trigeminal neuralgia is more difficult because of adhesions between the prosthesis, such as the Teflon sling, and the surrounding structures, including the blood vessels, in addition to common post-open surgery adhesions. A case of a patient with recurrent trigeminal neuralgia is presented. Preoperative evaluation of the compression of the trigeminal nerve is important. The pre-existing prosthesis does not necessarily need to be removed entirely.


Emerging strains of porcine epidemic diarrhoea virus (PEDv) in Mexico.
As an emerging disease, the porcine epidemic diarrhoea virus has caused substantial economic losses to the pork industry in Mexico, leading to piglet mortality rates of up to 100%. For detection, sequencing and genetic characterization of the virus, 68 samples of one-week-old piglets from pork farms in 17 states of Mexico were analysed. In total, 53 samples were positive by real-time RT-PCR, confirming the presence of the virus in 15 states. Twenty-eight samples from 10 states were amplified by endpoint RT-PCR, and 20 sequences of the spike gene were obtained. A phylogenetic analysis based on the spike gene demonstrated that all Mexican strains are in Group II and are classified as non-Indel-S emerging variants. Three strains showed amino acid insertions: PEDv/MEX/GTO/LI-DMZC15/2015 and PEDv/MEX/QRO/LI-DMZC45/2016 showed one amino acid insertion (424 Y425 and 447 D448 , respectively), and PEDv/MEX/QRO/LI-DMZC49/2019 showed one and two amino acid insertions (422 C423 and 537 SQ538 ), with the second insertion in the COE region. These results provide evidence of the prevalence of emerging, non-Indel-S strains of the virus are currently circulating in Mexico during 2016-2018, when three of which have amino acid insertions: PEDv/MEX/GTO/IN-DMZC15/2015 and PEDv/MEX/QRO/IN-DMZC45/2016 have one amino acid insertion each (424 Y425 and 447 D448 , respectively), and PEDv/MEX/QRO/IN-DMZC49/2019 has one (422 C423 ) and two amino acid insertions (537 SQ538 ), the latter being in the COE region, which could generate new antigenic variants.


Presumptive partial atrial standstill secondary to atrial cardiomyopathy in a Greyhound.
Persistent atrial standstill is a rare arrhythmia in both human and veterinary patients. In recent decades, cases of partial atrial standstill have been recognized in humans. We describe a case of presumptive partial atrial standstill in a Greyhound, in which there was disparate left and right atrial electromechanical function and rapid progression to congestive heart failure over the span of fourteen weeks. An atrial cardiomyopathy characterized by severe, diffuse, fibrofatty replacement of the atrial myocardium was identified histologically.


Hybridoma growth in a new generation hollow fibre bioreactor: antibody productivity and consistency.
This paper analyses the performance of MAbMax(TM)/Tricentric(TM), a new generation hollow fibre bioreactor, for hybridoma growth and antibody productivity, the down stream processing of monoclonal antibody harvests throughout the run and the further control of antibody quality consistency. Handling and process parameters were optimised using a mouse hybridoma, IgG1(K) secretor, and then confirmed with several other hybridomas. Cells were kept at optimal viability during an unusually long period of time and a continuously high production of antibodies was detected over several months. Foetal bovine serum concentration was reduced to 1\% and the effects of weaning of cells from serum were monitored in terms of cell metabolism and antibody productivity. Antibody harvests collected at regular intervals throughout the run (2 to 12 weeks) were purified using affinity chromatography on a recombinant protein A/G matrix and then analysed in terms of antigen binding properties, isoelectric forms and oligosaccharide structures, in order 1) to control antibody quality consistency as a function of time and serum concentration and 2) to compare antibody characteristics as a function of culture conditions, in vitro bioreactor cultivation versus in vivo mouse ascite cultivation.


Autoimmunity and normal immune functions in aged humans.
The high frequency of ANA, A-LDL and RF in advanced age suggests that AABs are present in the majority of aged subjects. CIC incidence determined by three methods is far below AAB incidence; only the Clq solubility test suggests an increased CIC incidence in aged as compared to young subjects. Simultaneous occurrence of AABs of different specificities or CIC determined by two or three methods is rare and both AAB and CIC levels are usually low. AAB prevalence in CIC-positive individuals seems to depend on the specificity of the AAB. CIC positivity is associated with relatively low Clq concentrations; however, usually not with Clq concentrations below the normal range. Neither ANA nor CIC positivity seems to correlate with DNA synthetic response to PHA, but ANA positivity may be associated with low responses to allogeneic cells. ANA positivity and, to a lesser extent, CIC positivity seems to be connected with enhanced killer cell activity. The concept of some AABs and CIC as autoregulatory factors of the humoral immune system compensating for the thymus-dependent regulation in old age is stressed.


Interaction of selected cosolvents with bovine alpha-lactalbumin.
Alpha-lactalbumin constitutes about 3% of bovine milk proteins. The preferential solvent interactions between selected cosolvents (sorbitol, sucrose and glycerol) and alpha-lactalbumin at pH 7.5 was determined using precision densitimetry. The preferential interaction parameter (xi(3)) and other thermodynamic parameters were calculated at different solvent concentrations. The xi(3) parameter was maximum at 30%, 45% and 40% (w/v) concentrations with the values of -0.282g/g, -0.171g/g and -0.299g/g for sorbitol, sucrose and glycerol, respectively. Thus the principal driving energy in the system being preferential hydration and mutual exclusion of bulk solvent. There was only a marginal change in the CD spectra of the protein with these cosolvents indicating the integrity of secondary structures. The results of thermal denaturation measurements indicated an increase in thermal stability of alpha-lactalbumin with these cosolvents. In the presence of 30% sorbitol there was an increase in the apparent thermal transition temperature (apparent T(m)) from 65 to 71 degrees C. These results indicate that the selected cosolvents in this study stabilizes alpha-lactalbumin without altering the structure of the protein.


Comprehensive Genotyping and Phenotyping Analysis of GUCY2D-Associated Rod- and Cone-Dominated Dystrophies.
To describe the genetic and clinical spectrum of GUCY2D-associated retinopathies and to accurately establish their prevalence in a large cohort of patients. Retrospective case series. Institutional study of 47 patients from 27 unrelated families with retinal dystrophies carrying disease-causing GUCY2D variants from the Fundación Jiménez Díaz hospital dataset of 8000 patients. Patients underwent ophthalmological examination and molecular testing by Sanger or exome sequencing approaches. Statistical and principal component analyses were performed to determine genotype-phenotype correlations. Four clinically different associated phenotypes were identified: 66.7% of families with cone/cone-rod dystrophy, 22.2% with Leber congenital amaurosis, 7.4% with early-onset retinitis pigmentosa, and 3.7% with congenital night blindness. Twenty-three disease-causing GUCY2D variants were identified, including 6 novel variants. Biallelic variants accounted for 28% of patients, whereas most carried dominant alleles associated with cone/cone-rod dystrophy. The disease onset had statistically significant differences according to the functional variant effect. Patients carrying GUCY2D variants were projected into 3 subgroups by allelic combination, disease onset, and presence of nystagmus or night blindness. In contrast to patients with the most severe phenotype of Leber congenital amaurosis, 7 patients with biallelic GUCY2D had a later and milder rod form with night blindness in infancy as the first symptom. This study represents the largest GUCY2D cohort in which 4 distinctly different phenotypes were identified, including rare intermediate presentations of rod-dominated retinopathies. We established that GUCY2D is linked to about 1% of approximately 3000 molecularly characterized families of our cohort. All of these findings are critical for defining cohorts for inclusion in future clinical trials.


Frequency, severity and determinants of functional limitations in older adults with joint pain and comorbidity: results of a cross-sectional study.
Older adults with joint pain and comorbidity are especially at risk of becoming functionally impaired. Therefore, we studied the frequency and severity of functional limitations and identified potential modifiable determinants that may reduce functional limitations. A prospective cohort study of older adults (≥65 years) with joint pain and comorbidity provided cross-sectional baseline data (n=407). Based on the International Classification of Functioning, Disability and Health (ICF) model, we measured Physical Functioning; PF, (Instrumental) Activities of Daily Living; (I)ADL, and participation. Apart from examining the frequency and severity, we identified determinants of functional limitations with multivariate regression analyses, by adding determinants in two steps: (1) only physical determinants, (2) physical and psychosocial determinants. Limitations in PF, ADL, IADL and participation were present in 66%, 31%, 61% and 47% of the participants, respectively. About 22% reported limitations on all four measures. Of the physical determinants, especially frailty and higher pain intensity were related to functional limitations. Remarkably, adding psychosocial determinants to the model weakened some of these relations. The psychosocial determinants were especially related to poor PF (i.e. anxiety symptoms, activity avoidance and poor general health perception) and participation restrictions (i.e. depressive symptoms, less social support). An inverse relation was present between self-efficacy and both outcomes. In conclusion, our sample reported substantial levels of functional limitations. More depressive symptoms, more activity avoidance and less social support were indicative of more functional limitations, whereas higher perceived self-efficacy was indicative of better functioning. Such psychosocial determinants should receive more attention in research.


The survival impact of systematic lymphadenectomy in endometrial cancer with the use of propensity score matching analysis.
We sought to evaluate whether patients with endometrial cancer in the Surveillance, Epidemiology, and End Results database who underwent lymphadenectomy demonstrate improved survival. The study population comprised 50,969 patients. The 3-year cause-specific survival was tested by using propensity score matching (PSM) analysis. The PSM analysis generated a balanced, matched cohort in which baseline characteristics were not significantly different. The benefit of systematic lymphadenectomy appears to be significant for presumed stage I International Federation of Gynecology and Obstetrics grade 3 cancers and presumed stages II-III cancer. The omission of lymphadenectomy in stage I did not appear to show a deleterious survival consequence if the differentiation grade was moderate (grade 2) or well (grade 1). Using PSM analysis, our results show no evidence of benefit in terms of survival for systematic lymphadenectomy in women with stage I endometrial cancer, except for grade 3 cancers.


Meniscal repair and regeneration: Current strategies and future perspectives.
The management of meniscal injuries remains difficult and challenging. Although several clinical options exist for the treatment of such injuries, complete regeneration of the damaged meniscus has proved difficult due to the limited healing capacity of the tissue. With the advancements in tissue engineering and cell-based technologies, new therapeutic options for patients with currently incurable meniscal lesions now potentially exist. This review will discuss basic anatomy, current repair techniques and treatment options for loss of meniscal integrity. Specifically, we focus on the possibility and feasibility of the latest tissue engineering approaches, including 3D printing technologies. Therefore, this discussion will facilitate a better understanding of the latest trends in meniscal repair and regeneration, and contribute to the future application of such clinical therapies for patients with meniscal injuries.


Lipopeptides from an isolate of Bacillus subtilis complex have inhibitory and antibiofilm effects on Fusarium solani.
Bacillus subtilis species complex is known as lipopeptide-producer with biotechnological potential for pharmaceutical developments. This study aimed to identify lipopeptides from a bacterial isolate and evaluate their antifungal effects. Here, we isolated and identified a lipopeptide-producing bacterium as a species of Bacillus subtilis complex (strain UL-1). Twenty lipopeptides (six iturins, six fengycins, and eight surfactins) were identified in the crude extract (CE) and fractions (F1, F2, F3, and F4), and the highest content of total lipopeptides was observed in CE and F2. The chemical quantification data corroborate with the hemolytic and antifungal activities that CE and F2 were the most hemolytic and inhibited the fungal growth at lower concentrations against Fusarium spp. In addition, they caused morphological changes such as shortening and/or atypical branching of hyphae and induction of chlamydospore-like structure formation, especially in Fusarium solani. CE was the most effective in inhibiting the biofilm formation and in disrupting the mature biofilm of F. solani reducing the total biomass and the metabolic activity at concentrations ≥ 2 µg/mL. Moreover, CE significantly inhibited the adherence of F. solani conidia on contact lenses and nails as well as disrupted the pre-formed biofilms on nails. CE at 100 mg/kg was nontoxic on Galleria mellonella larvae, and it reduced the fungal burden in larvae previously infected by F. solani. Taken together, the lipopeptides obtained from strain UL-1 demonstrated a potent anti-Fusarium effect inducing morphological alterations and antibiofilm activities. Our data open further studies for the biotechnological application of these lipopeptides as potential antifungal agents. KEY POINTS: • Lipopeptides inhibit Fusarium growth and induce chlamydospore-like structures. • Lipopeptides hamper the adherence of conidia and biofilms of Fusarium solani. • Iturins, fengycins, and surfactins were associated with antifungal effects.


Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis in Canada.
To describe clinical characteristics of Canadian patients with myelin-oligodendrocyte glycoprotein immunoglobulin-G optic neuritis (MOG-IgG ON). Retrospective observational case series of MOG-IgG seropositive patients with ON referred to tertiary neuro-ophthalmology practices. Outcome measures included clinical characteristics, radiologic findings, and visual outcomes. Forty-six eyes of 30 patients were included. Twenty-three (76.7%) were women, mean onset age was 40.7 years (range 16-77), and most were Caucasian. Seventeen (56.7%) presented with their first ON episode. Sixteen (53.3%) had bilateral eye involvement. Isolated ON without associated neurological symptoms occurred in 90.0%. In 22 patients with acute ON (seen within 1 month of onset), presenting mean visual acuity (VA) was 20/258 (logMAR 1.11), mean deviation (MD) on Humphrey visual fields was -16.90 ± 10.83 dB, and peripapillary retinal nerve fiber layer (RNFL) thickness on ocular coherence tomography (OCT) was 164.23 ± 46.53 um. Orbital magnetic resonance imaging (MRI) within 1 month of symptom onset for 19 patients demonstrated orbital optic nerve enhancement in 11 (57.9%) and perineural enhancement in 11 (57.9%). Brain MRI was normal in 28 (93.3%) patients. Twenty out of 22 patients with acute presentation were treated with high-dose glucocorticoids and 5 with plasma exchange in addition to corticosteroids. Long-term immunosuppression was utilized in 9 (30%) out of all 30 patients. Final VA was 20/30 (logMAR 0.18), MD was -7.17 ± 8.85 dB, and RNFL thickness was 72.15 ± 20.16 um. MOG-IgG ON in Canada has a variable presentation with most patients having substantial initial vision loss with good recovery. This is the largest characterization of the disease in Canada to date.


Origin of Limiting and Overlimiting Currents in Bipolar Membranes.
Bipolar membranes (BPMs), a special class of ion exchange membranes with the unique ability to electrochemically induce either water dissociation or recombination, are of growing interest for environmental applications including eliminating chemical dosage for pH adjustment, resource recovery, valorization of brines, and carbon capture. However, ion transport within BPMs, and particularly at its junction, has remained poorly understood. This work aims to theoretically and experimentally investigate ion transport in BPMs under both reverse and forward bias operation modes, taking into account the production or recombination of H+ and OH-, as well as the transport of salt ions (e.g., Na+, Cl-) inside the membrane. We adopt a model based on the Nernst-Planck theory, that requires only three input parameters─membrane thickness, its charge density, and pK of proton adsorption─to predict the concentration profiles of four ions (H+, OH-, Na+, and Cl-) inside the membrane and the resulting current-voltage curve. The model can predict most of the experimental results measured with a commercial BPM, including the observation of limiting and overlimiting currents, which emerge due to particular concentration profiles that develop inside the BPM. This work provides new insights into the physical phenomena in BPMs and helps identify optimal operating conditions for future environmental applications.


Further advances in the management of malignant teratomas of the testis and other sites.
Between 1979 and 1982, 69 men with metastatic malignant teratoma completed sequential combination chemotherapy (POMB/ACE). Although two-thirds of these patients initially had advanced and bulky disease, life-table analysis projects a survival of 83%. Multivariate analysis indicates that the strongest predictor of survivals is not the clinical and radiological extent of disease but the initial serum concentration of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP). In patients presenting with HCG levels below 50 000 IU/l and AFP levels below 500 kU/l the survival in 47 patients was 96%. This contrasts with the survival projected at 56% in 22 patients presenting with tumour markers at higher concentrations.


Prehospital tourniquet use in civilian extremity trauma: an Australian observational study.
Prehospital tourniquets (PHTQ) for trauma have been shown to be safe and effective in the military environment and in some civilian settings. However, the supporting civilian data are mostly from North America with a differing case mix and trauma system and may not be applicable to the Australian environment. The aim of this study is to describe our initial experience with PHTQ from safety and efficacy viewpoints. Retrospective review of all patients with PHTQ from 1 August 2016 to 31 December 2019 was conducted. Data were matched from the RMH Trauma Registry and Ambulance Victoria Registry. Clinical presentation including prehospital observations, PHTQ times, limb outcomes and complications are described. Thirty-one cases met inclusion criteria, for whom median age was 37 (IQR: 23.9-66.3), median ISS 17 (13-34) and 80.6% were male. The majority (n = 19, 61.3%) were as a result of road traffic crash, and six (19.4%) from penetrating mechanisms, usually glass. Over a quarter (29.0%) suffered a traumatic amputation. The median prehospital SBP was 100 (IQR: 80-110), the median prehospital HR was 101 (IQR: 77.0-122.3) and was the median PHTQ time was 124 min (IQR: 47-243). Complications attributable to the tourniquet were seen in 4/30 cases (13.3%). This Australian series differs from North American civilian PHTQ series with a lower penetrating trauma rate and longer PHTQ times. Despite this, complication rates are within the published literature's range. Concerns regarding limited transferability of overseas studies to the Australian context suggests that ongoing audit is required.


Predictors of emergency department visit among people with dementia in Taiwan.
We aimed to identify predictors of emergency department (ED) visit by people with dementia (PWDs) and their caregivers with a one-year follow-up in a country with public health system. Data were collected from a national dementia registration survey. Andersen's Behavioral Model of Health Services Use was used. Variables such as demographic data of PWDs and their caregivers, caregivers' monthly income, the relationship between PWD and caregivers, the severity of dementia (clinical dementia rating, CDR), physical comorbidities, cognitive function (mini-mental state examination, MMSE), and activities of daily living of PWDs, the caregiver burden, and neuropsychiatric symptoms (assessed by the Neuropsychiatric Inventory Questionnaire) were included in the analyses. A total of 1,227 PWDs-caregiver dyads completed the survey, and 405 (33%) of PWDs visited ED during the one-year follow-up. Multivariable logistic analyses revealed that older age of PWDs (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01-1.05), more severe dementia (CDR; OR = 1.42, 95% CI = 1.09-1.86), higher cognitive function (MMSE; OR = 1.04, 95% CI = 1.01-1.07), and having a female family caregiver (OR = 1.50, 95% CI = 1.13-2.01) were predictors of ED visit. Our study results provided information for healthcare providers and policy makers to target models of care that support PWD and their caregivers and reduce the need for ED visits.


Regulatory T-cell-derived interleukin-15 shapes cytotoxic T cell memory.
It is well known that regulatory T-cells (Tregs) are required to prevent autoimmunity, but they may also have some less-well understood immune-stimulatory effects. In particular, in CD8+ T-cell responses Tregs select high-affinity clones upon priming and promote memory by inhibiting inflammation-dependent generation of short-lived effector cells. In the current issue of the European Journal of Immunology [Eur. J. Immunol. 2023. 53: 2149400], Madi et al. report the surprising finding that human and murine FOXP3+ Tregs are a physiologically relevant source of IL-15, a homeostatic cytokine that promotes antigen-independent maintenance of CD8+ memory T-cells. In mice that lack IL-15 selectively in FOXP3+ Tregs the authors show that the composition of the CD8+ T-cell memory pool is altered in the absence of Treg-derived IL-15, since a subset of terminally effector memory cells is drastically reduced. Otherwise Treg-derived IL-15 is dispensable for antiviral immune responses and the generation of anti-viral CD8+ memory T-cells. These findings add to our understanding of the multifaceted role of Tregs in immune responses, and how IL-15 derived from different cellular sources maintains anti-viral T-cell memory.


Advances in processing of surface myoelectric signals: Part 1.
During sustained voluntary or electrically elicited muscle contractions the surface myoelectric signal is nonstationary and it undergoes progressive changes reflecting the modifications of the motor unit action potentials and their propagation velocity. In particular, during sustained electrical stimulation, the evoked signals show progressive amplitude, time scaling and shape modification. The quantitative evaluation of these changes is important for non-invasive muscle characterisation and may be performed in either the time or frequency domain using parametric and nonparametric spectral analysis as well as alternative methodologies. The paper introduces the detection techniques, reviews and compares the methods of spectral estimation based on FFT and autoregressive models, and discusses their applications and limitations in extracting information from the surface myoelectric signal with particular regard to myoelectric manifestations of localised muscle fatigue during sustained contractions.


Novel eicosanoid pathways: the discovery of prostacyclin/6-keto prostaglandin F1alpha and the hepoxilins.
This article reviews a lecture I was honored to present at the Leon Wolfe Symposium in Montreal on March 25, 2004. The lecture described my research career, which started with my interaction with Wolfe at the Montreal Neurological Institute as a postdoctoral fellow and research associate and was followed by additional research discoveries after I left Montreal for my first academic position at the Research Institute, The Hospital for Sick Children and University of Toronto. The article consists of two parts. The first part involves the discovery (in Wolfe's laboratory) of a new pathway of arachidonic acid, in which a bicyclic prostanoid structure (later called prostacyclin by John Vane and his group) was described, and its further development in Toronto, which led to the discovery of the conversion of the bicyclic prostanoid into 6-keto prostaglandin F1alpha. The second part deals with the hepoxilin pathway, a pathway I discovered during a sabbatical leave in Japan with Professor Shozo Yamamoto, which was followed by a stay of several months in the laboratory of Professor Bengt Samuelsson in Sweden. I deal with the historical aspects of both pathways and end with interesting novel aspects of hepoxilin stable antagonist analogs in the treatment of solid tumors in experimental animals.