Increased burst firing in substantia nigra pars reticulata neurons and enhanced response to selective D2 agonist in hemiparkinsonian rats after repeated administration of apomorphine.
Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, intraperitoneal, i.p.) twice daily for 6 days enhanced the rotation induced by apomorphine from 341 turns/hour at the beginning to 755 turns/hr at the end. At the same time, the response to selective D2 agonist quinpirole (0.26 mg/kg, i.p.) was also enhanced from 203 to 555 turns/hr. Extracellular single unit recording revealed no significant difference in the basal firing rates of substantia nigra pars reticulata (SNr) neurons between the ipsilateral and contralateral side of the 6-OHDA lesion regardless of the repeated administrations of apomorphine. In SNr of the lesion side, the units with burst firing pattern were found more frequently after repeated administrations of apomorphine and the suppressive effect of quinpirole on the firing rate was enhanced. These findings suggest that the increased percentage of the burst units is the important electrophysiological change in the development of enhanced response to selective D2 agonist.


Mapping of the gene coding for Epstein-Barr virus-determined nuclear antigen EBNA3 and its transient overexpression in a human cell line by using an adenovirus expression vector.
The open reading frame which lies within the Epstein-Barr virus (EBV) T2 cDNA isolated by Bodescot et al. (M. Bodescot, O. Brison, and M. Perricaudet, Nucleic Acids Res. 14:2611-2620, 1986) was inserted into a eucaryotic expression vector containing a strong adenovirus promoter. The T2 cDNA contains viral genomic sequences from the short BLRF3 open reading frame fused to the adjacent BERF1 long open reading frame. After transfection of human cells, the recombinant plasmid directed the expression of a 140-kilodalton protein. The expressed protein had the same molecular weight, subcellular localization, and immunological characteristics as the EBV-determined nuclear antigen EBNA3, which is made in lymphocytes latently infected with EBV. Immunoprecipitation of extracts of transfected cells labeled with [32P]phosphoric acid showed that the EBNA3 protein is phosphorylated.


Combined Palmer Type 1A and 1B Traumatic Lesions of the Triangular Fibrocartilage Complex A New Category.
We present a series of eight patients who underwent wrist arthroscopy for presumed solitary tears of the triangular fibrocartilage (TFC) and were, instead, found to have combined 1A (central tear) and 1B (ulnar avulsion) tears. The Palmer Classification does not currently categorize this combined pattern. All but one patient had a traumatic injury. Each subject had preoperative radiographs and MRI scans. TFC tears were evident on all MRI scans, though only one was suggestive of a combined tear pat - tern. Surgical management included arthroscopic central tear debridement and ulnar peripheral repair. Average follow-up was 22 months. Grip strength in the affected hand improved from 16% deficit as compared to the unaffected side, to 3.5% deficit postoperatively (p = 0.003), and visual analog scores (VAS) decreased from an average of 7.1/10 preoperatively to 2.3/10 postoperatively (p < 0.001). There was no statistically significant change in wrist range of motion (ROM), however. Arthroscopic debridement of the central perforation (1A lesion) with concomitant repair of the ulnar detachment (1B lesion) resulted in functional and symptomatic improvement. This combined 1A/1B TFC injury is not reliably diagnosed preoperatively and should be considered a new subset in the Palmer classification, as this will raise awareness of its presence and assist in preoperative planning of such lesions.


Genome analysis technologies: towards species identification by genotype.
Traditional identification of species has been based on phenotypic traits, although it is clear that, theoretically, genotype-based classification is more accurate. This is especially the case for microorganisms which possess less identifiable traits and are more easily influenced by environment. Therefore, technology that allows identification of species based on genotype is highly desirable. Whole genome sequencing can provide a sufficient amount of information and can be determinative for this purpose but is very impractical for routine use. Thus, a competent technology is needed that allows a reproducible reduction in the amount of information required about a whole genome, while still providing sufficiently accurate identification. It is almost imperative for such a technology to be of a high cost-performance and of easy handling. Universality and portability are also strongly desired. Based on these criteria, the current state of genome analysis technologies are reviewed. Among various methodologies discussed here, amplified fragment length polymorphism (AFLP), genome profiling (GP) and microarrays are the subject of particular attention. As species identification is a base for most fields of biology including microbiology, ecology, epidemiology and for various biotechnologies, it is of paramount importance to establish a more efficient, easily handled and more objective methodology, in parallel with conventional phenotype-based methodologies. GP is currently considered to have the most optimal nature for identification of species since it can reproducibly reduce a huge amount of genome information to a manageable size by way of random polymerase chain reaction and can extract a sufficient amount of information for species identification from the DNA fragments thus profiled by temperature gradient gel electrophoresis. The potential ability of DNA microarrays for this purpose is also discussed and promises much for the future.


Pattern of Chronic Venous Insufficiency among Patients Presenting to a Vascular Surgery Clinic in Low- to Middle-Income Countries (LMIC): A Cross-Sectional Study.
Objective: To measure the pattern and severity of chronic venous insufficiency (CVI) in patients presenting to a vascular surgery clinic in Pakistan. Materials and Methods: This cross-sectional study has examined patients presenting with CVI for the first time. Patients were assessed for severity of the disease using clinical, etiological, anatomical and pathological (CEAP) score and venous clinical severity score (VCSS). Patients were then divided into two groups depending on the severity of the disease: 'mild/moderate' CVI if the CEAP classification was ≤C3 or VCSS was <5 and 'severe' if CEAP classification was >3 or VCSS was ≥5. Both groups were then compared to determine the factors associated with the more 'severe' form of CVI. Results: During the study duration, 121 patients presented with CVI with mean age of 47.83±12.02 years; 74 (61.2%) were female. Mean body mass index of the patients was 32.49±18.3 kg/m2. Mean VCSS was 5.49±3.84, indicating most patients presented with the severe form of CVI. Field workers were determined to be three to five times more likely to present with severe CVI compared to housewives and office workers. Conclusion: Majority of the patients who presented to a tertiary care facility had the severe form of CVI. Thus, there is a need to raise awareness on this disease at community level.


The effects of neuroleptics on attention in adolescent schizophrenics.
In contrast to studies of adult psychiatric patients, there was no striking difference between vigilance task performance by 11 newly diagnosed, previously untreated adolescent schizophrenics and that of 58 nonpsychotic adolescent comparison subjects. Neuroleptic treatment failed to improve the performance of the schizophrenic subjects. Sedation, a frequent side effect, was associated with significant prolongation of reaction time and an increase in error rate. Attentional characteristics of adolescent schizophrenics appear to resemble those of other disturbed children. Their response to neuroleptics appears to be limited and the deleterious effects of sedation on attention may well outweigh any clinical benefit attributable to sedation. Findings are discussed in terms of methodology and age-related characteristics.


Laboratory and Field Evaluations of Polyacrylamide Hydrogel Baits Against Argentine Ants (Hymenoptera: Formicidae).
The development of effective baits to control the Argentine ant, Linepithema humile (Mayr), has been problematic because foragers prefer sweet liquids, while many toxicants are insoluble in water and liquid baits are generally difficult to deliver. The incorporation of thiamethoxam and sucrose solutions into a water-absorbing polyacrylamide hydrogel provides a unique and novel carrier and method of application for liquid baits. Formulations of thiamethoxam affected the size of the hydrogels, and sucrose solutions containing 0.0003% technical thiamethoxam provided hydrogels as large as those made with 25% sucrose solution or deionized water. Concentrations of thiamethoxam as low as 0.000075% in the hydrogels provided 50% kill of workers within 3 d in a laboratory setting. In small colony studies, baiting with 0.00015 and 0.000075% thiamethoxam hydrogels provided 100% mortality of workers and queens within 8 d. An enzyme-linked immunosorbent assay indicated that thiamethoxam was absorbed into the interior of the polyacrylamide matrix. The water loss rates of the hydrogels were dependent upon the relative humidity. Polyacrylamide hydrogels with >50% water loss were less attractive to ants. Field studies in highly infested areas indicated that concentrations of 0.0006 or 0.0018% thiamethoxam were more effective than 0.00015%. Hydrogels may provide a cost-effective alternative to providing aqueous baits to control Argentine ants.


Moloney murine leukemia virus integrase and reverse transcriptase interact with PML proteins.
Pull-down assay and co-immunoprecipitation of cell extracts in which the integrase or reverse transcriptase of Moloney murine leukemia virus was transiently expressed showed that both enzymes interacted with PML proteins. In infected cells, interaction between the integrase and PML was also observed. Transient expression of PIASy and SUMO proteins facilitated SUMOylation of the integrase but had no apparent effects on the interaction with PML. A FLAG-tagged integrase co-localized with PML protein possibly in the PML body. Knockdown of PML by small interfering RNA resulted in reduced viral cDNA levels and integration efficiency. This suggested that PML proteins activated reverse transcription.


High-rising epiglottis in children: should it cause concern?
An omega-shaped epiglottis is frequently associated with laryngomalacia. However, an elongated high-rising epiglottis can represent a normal variation of the larynx in a majority of pediatric patients. It is important to consider this in a healthy child with no complaints apart from the sensation of a foreign body in throat. This will avoid triggering any unnecessary investigation or treatment. An elongated epiglottis projecting in the oropharynx can appear as a foreign body and be a source of anxiety for the parents as well as the unaware family practitioner. We present such a case, with a brief discussion of the pediatric larynx and the omega-shaped epiglottis.


Combined Treatment with Demecolcine and 6-Dimethylaminopurine during Postactivation Improves Developmental Competence of Somatic Cell Nuclear Transfer Embryos in Pigs.
This study determined the effects of postactivation treatment with demecolcine and/or 6-dimethylaminopurine (6-DMAP) on in vivo and in vitro developmental competence of somatic cell nuclear transfer (SCNT) embryos in pigs. SCNT embryos were treated for 4 hours with 0.4 µg/mL demecolcine, 2 mM 6-DMAP, or both after electric activation, then transferred to surrogate pigs or cultured for 7 days. The formation rate of SCNT embryos with a single pronucleus was higher in combined treatment with demecolcine and 6-DMAP (95.2%) than treatment with demecolcine alone (87.1%). Blastocyst formation of SCNT embryos was significantly increased in combined treatment with demecolcine and 6-DMAP (48.7%) compared with demecolcine (22.2%) or 6-DMAP alone (37.3%). Fluctuation of maturation promoting factor activity showed different patterns among various postactivation treatments. Pregnancy was established in 1 of 5 surrogates after transfer of SCNT embryos that were treated with demecolcine and 6-DMAP. The pregnant surrogate delivered one healthy live piglet. The results of our study demonstrated that postactivation treatment with demecolcine and 6-DMAP together improved preimplantation development and supported normal in vivo development of SCNT pig embryos, probably influencing MPF activity and nuclear remodeling, including induction of single pronucleus formation after electric activation.


Normal birth: social-medical model.
Understanding the underlying sociological models of pregnancy and childbirth can help policy makers, midwives and new mothers to put issues around 'normal birth' into perspective. Being aware of the medical and social model of childbirth also helps us understand why some people seeing the world from one particular perspective cannot 'see' or comprehend solutions to a problem that are based on an opposing perspective. Whether you regard pregnancy as a normal event in a woman's life cycle or as a risky event that can only be defined as safe in retrospect, gives strong clues as to how you see the world. It is important to be aware that models are constructed to help us understand the world; they are abstract, not 'real', although they can be real in their consequences.


DLP-printed GelMA-PMAA scaffold for bone regeneration through endochondral ossification.
Intramembranous ossification (IMO) and endochondral ossification (ECO) are two pathways of bone regeneration. The regeneration of most bone, such as limb bone, trunk bone, and skull base bone, mainly occurs in the form of endochondral ossification, which has also become one of the effective ways for bone tissue engineering. In this work, we prepared a well-structured and biocompatible methacrylated gelatin/polymethacrylic acid (GelMA/PMAA) hydrogel by digital light processing (DLP) printing technology, which could effectively chelate iron ions and continuously activate the hypoxia-inducible factor-1 alpha (HIF-1α) signaling pathway to promote the process of endochondral ossification and angiogenesis. The incorporation of PMAA endowed the hydrogel with remarkable viscoelasticity and high efficacy in chelation of iron ions, giving rise to the activation of HIF-1α signaling pathway, improving chondrogenic differentiation in the early stage, and facilitating vascularization in the later stage and bone remodeling. Therefore, the findings have significant implications on DLP printing technology of endochondral osteogenesis induced by the iron-chelating property of biological scaffold, which will provide an effective way in the development of novel bone regeneration.


Microwave synthesis of CdSe and CdTe nanocrystals in nonabsorbing alkanes.
Controlling nanomaterial growth via the "specific microwave effect" can be achieved by selective heating of the chalcogenide precursor. The high polarizability of the precursor allows instantaneous activation and subsequent nucleation leading to the synthesis of CdSe and CdTe in nonmicrowave absorbing alkane solvents. Regardless of the desired size, narrow dispersity nanocrystals can be isolated in less than 3 min with high quantum efficiencies and elliptical morphologies. The reaction does not require a high temperature injection step, and the alkane solvent can be easily removed. In addition, batch-to-batch variance in size is 4.2 +/- 0.14 nm for 10 repeat experimental runs. The use of a stopped-flow reactor allows near continuous automation of the process leading to potential industrial benefits.


Optometry research. Part 3: Faculty publications.
I compared the production of faculty-produced publications among the U.S. schools and colleges of optometry and the Department of Veterans Affairs (VA) Optometry Service. These publication rates were viewed against the schools' rankings in National Eye Institute (NEI) funding (see Part 2), student/faculty ratios, faculty salaries, and the presence of a graduate degree program. The schools and the VA grouped into three levels of publication production with five of first rank, four of middle rank, and eight of lower rank. The five leading producers in the period 1982 through 1991 were Berkeley, Alabama, Houston, VA, and State University of New York (SUNY). Since 1982 VA optometrists have authored the largest number of articles published in the Journal of the American Optometric Association and since 1985 have been the leading group of continuing education (CE) lecturers at the Academy.


[Microangiographic findings in experimental intestinal anastomoses].
Microangiography of anastomosis at the rat colon and the pig jejunum did reveal the postoperative state of vessel regeneration. Findings for evaluation were avascular areas, dislocation and dilatation of vessels, vessel break, vessel-anastomosis to the opposite site and to adhesions as well as the complete regeneration of the vessel architecture. A suture technique leading to correct apposition of the wound edges without destroying the circulation will be followed by an almost complete regeneration of the vessel architecture.


Vestibulo-oculomotor disturbances caused by occupational hazards.
Air-borne pollutants inhaled by workers when welding or in environments containing hydrocarbon solvents can result in occult CNS disturbances. The disturbances can appear as a psycho-organic syndrome, but early symptoms such as vertigo or dizziness may indicate the presence of a vestibular involvement.


[Surgery in severe forms of allergic eye diseases].
Surgical treatment is performed in allergic eye diseases when drug treatment fails and the disease leads to conjunctival, corneal or palpebral disorders. Surgery procedures can be divided into early (surgery on palpebral conjunctiva, surgery on cornea) and late ones (decreasing tears outflow, plastic surgery on eyelids, cul de sac).


Novel refractive index biosensing of microcontact printed molecules on lithium niobate.
This work demonstrates, for the first time, the use of lithium niobate as a biosensor that detects local refractive index changes triggered by the presence of biomolecules on its surface. The sensitivity of the sensor was found to be 242±16 nm/RIU. As a case study, we immobilized proteins (IgG antibodies) using micro-contact printing to demonstrate sensing capabilities of the device. The validated proof of concept lays a foundation for developing lithium niobate based novel optical biosensors.


Mental Health Symptoms and Associations with Tobacco Smoking, Dependence, Motivation, and Attempts to Quit: Findings from a Population Survey in Germany (DEBRA Study).
This study aimed to estimate prevalence rates of mental health symptoms (anxiety, depression, and overall psychological distress) by tobacco smoking status, and associations between such symptoms and the level of dependence, motivation, and attempts to quit smoking in the German population. Cross-sectional analysis of data from six waves of a nationally representative household survey collected in 2018/19 (N = 11,937 respondents aged ≥18). Mental health symptoms were assessed with the Patient Health Questionnaire-4. Associations with smoking status, dependence, motivation to quit, and ≥1 past-year quit attempt (yes/no) were analysed with adjusted regression models among the total group, and among subgroups of current (n = 3,248) and past-year smokers (quit ≤12 months ago, n = 3,357). Weighted prevalence rates of mental health symptoms among current, former, and never smokers were: 4.1%, 2.4%, 2.5% (anxiety), 5.4%, 4.7%, 4.0% (depression), and 3.1%, 2.5%, 2.4% (psychological distress). Current versus never smokers were more likely to report symptoms of anxiety and depression. Smokers with higher versus lower levels of dependence were more likely to report higher levels of all three mental health symptoms. Higher versus lower levels of overall psychological distress were associated with a higher motivation to quit smoking and, among past-year smokers, with higher odds of reporting a past-year quit attempt. We found various relevant associations between mental health symptoms and smoking behaviour. Healthcare professionals need to be informed about these associations and trained to effectively support this vulnerable group in translating their motivation into abstinence.


Specificity evaluation of antibodies against human β3-adrenoceptors.
β(3)-Adrenoceptors are a promising drug target for the treatment of urinary bladder dysfunction, but knowledge about their expression at the protein level and their functional role is limited, partly due to a lack of well validated tools. As many antibodies against G-protein-coupled receptors, including those against β(3)- and other β-adrenoceptor subtypes, lack selectivity for their target, we have evaluated the specificity of five antibodies raised against the full-length protein of the human β(3)-adrenoceptor (H155-B01), its N-terminus (LSA4198 and TA303277) and its C-terminus (AB5122, Sc1472) in immunoblotting and immunocytochemistry. Our primary test system were Chinese hamster ovary cells stably transfected to express each of the three human β-adrenoceptor subtypes at near physiological levels (100-200 fmol/mg protein). None of the five antibodies exhibited convincing target specificity in immunoblotting with Sc1472 apparently being least unsuitable. In immunocytochemistry, LSA4198 and Sc1472 appeared most promising, exhibiting at least some degree of specificity. As these two antibodies have been raised against different epitopes (N- and C-terminus of the receptor, respectively), we propose that concordant staining by both antibodies provides the most convincing evidence for β(3)-adrenoceptor labelling in cyto- or histochemistry studies.


Maternal Relationship Insecurity and Depressive Symptoms as Moderators of Home Visiting Impacts on Child Outcomes.
The purpose of this study was to determine the extent to which maternal relationship insecurity and severe depressive symptoms moderate home visiting impacts on developmental and behavioral outcomes in 2-year old children. In an experimental trial of the Healthy Families Alaska home visiting program, families (N = 249) were randomly assigned to home visiting (n = 126) or community services as usual (n = 123). Maternal severe depressive symptoms (CES-D ≥ 24) and relationship insecurity were measured using the Center for Epidemiologic Studies Depression Scale and the Attachment Style Questionnaire at baseline. Child cognitive and psychomotor development and behavior problems were measured with the Bayley Scales of Infant Development and the Child Behavior Checklist at follow-up. The results revealed that home visiting significantly impacted three outcomes- child cognitive development, internalizing behavior, and externalizing behavior. Home visiting impacts were limited to subgroups defined by maternal depressive symptoms and relationship insecurity. Home visiting improved cognitive development (B = 6.02, p < .03), and decreased internalizing behavior (B = -3.83, p = .02) and externalizing behavior problems (B = -3.74, p = .03) in children of mothers with either severe depressive symptoms or high levels of discomfort with trust at baseline, but not both. Family engagement in home visiting seems to play a role in mediating these moderating effects. These findings reflect the importance of screening for maternal relationship insecurity and depressive symptoms to distinguish family subgroups likely to benefit from home visiting from those for whom an enhanced service model might be needed.


Effects of dietary quercetin on performance and cytochrome P450 expression of the cotton bollworm, Helicoverpa armigera.
Quercetin is ubiquitous in terrestrial plants. The cotton bollworm Helicoverpa armigera as a highly polyphagous insect has caused severe crop losses. Until now, interactions between this pest and quercetin are poorly understood at the biochemical and molecular levels. In this study, we investigated the in vivo effects of quercetin on performance of cotton bollworm and on cytochrome P450 (P450) expression. Deleterious effects of quercetin on the performance of the cotton bollworm, including growth, survival, pupation and adult emergence were observed after oral administration of 3 and 10 mg g(-1) quercetin to larvae since the third instar, whereas no significant toxic effect was found at 0.1 mg g(-1) quercetin treatment. Piperonyl butoxide treatment enhanced the toxicity of quercetin. In vitro metabolism studies showed that quercetin was rapidly transformed by gut enzymes of fifth instar larvae of the cotton bollworm. qRT-PCR results revealed that the effect of quercetin on P450 expression was tissue- and dose-specific. Quercetin regulated P450 expression in a mild manner, and it could serve as P450 inducer (CYP337B1, CYP6B6) or repressor (CYP337B1, CYP6B7, CYP6B27, CYP9A14, CYP6AE11, and CYP4M7). These findings are important for advancing our understanding of the biochemical and molecular response of insects to plant toxins and have implications for a smart pest control.


Acute pelvic inflammatory disease as a rare cause of acute small bowel obstruction.
Introduction: Small bowel obstruction (SBO) is a common presentation to emergency abdominal surgery. The most frequent causes of SBO are congenital, postoperative adhesions, abdominal wall hernia, internal hernia and malignancy. Patients: A 27-year-old woman was hospitalized because of acute abdominal pain, blockage of gases and stools associated with vomiting. Abdominal computed tomography showed an acute small bowel obstruction without any obvious etiology. In view of important abdominal pain and the lack of clear diagnosis, an explorative laparoscopy was performed. Diagnostic of pelvic inflammatory disease was established and was comforted by positive PCR for Chlamydia Trachomatis. Results: Acute small bowel obstruction resulting from acute pelvic inflammatory disease, emerging early after infection, without any clinical or X-ray obvious signs was not described in the literature yet. This infrequent acute SBO etiology but must be searched especially when there is no other evident cause of obstruction in female patients. Early laparoscopy is mostly advised when there are some worrying clinical or CT scan signs.


Input-specific maturation of NMDAR-mediated transmission onto parvalbumin-expressing interneurons in layers 2/3 of the visual cortex.
Parvalbumin-expressing (PV) GABAergic interneurons regulate local circuit dynamics. In terms of the excitation driving PV interneuron activity, the N-methyl-d-aspartate receptor (NMDAR)-mediated component onto PV interneurons tends to be smaller than that onto pyramidal neurons but makes a significant contribution to their physiology and development. In the visual cortex, PV interneurons mature during the critical period. We hypothesize that during the critical period, the NMDAR-mediated signaling and functional properties of glutamatergic synapses onto PV interneurons are developmentally regulated. We therefore compared the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and NMDAR-mediated synaptic responses before (postnatal days 15-20, P15-P20), during (P25-P40), and after (P50-P60) the visual critical period. AMPAR miniature excitatory postsynaptic currents (mEPSCs) showed a developmental decrease in frequency, whereas NMDAR mEPSCs were absent or showed extremely low frequencies throughout development. For evoked responses, we consistently saw a NMDAR-mediated component, suggesting pre- or postsynaptic differences between evoked and spontaneous neurotransmission. Evoked responses showed input-specific developmental changes. For intralaminar inputs, the NMDAR-mediated component significantly decreased with development. This resulted in adult intralaminar inputs almost exclusively mediated by AMPARs, suited for the computation of synaptic inputs with precise timing, and likely having NMDAR-independent forms of plasticity. In contrast, interlaminar inputs maintained a stable NMDAR-mediated component throughout development but had a shift in the AMPAR paired-pulse ratio from depression to facilitation. Adult interlaminar inputs with facilitating AMPAR responses and a substantial NMDAR component would favor temporal integration of synaptic responses and could be modulated by NMDAR-dependent forms of plasticity. NEW & NOTEWORTHY We show for the first time input-specific developmental changes in the N-methyl-d-aspartate receptor component and short-term plasticity of the excitatory drive onto layers 2/3 parvalbumin-expressing (PV) interneurons in the visual cortex during the critical period. These developmental changes would lead to functionally distinct adult intralaminar and interlaminar glutamatergic inputs that would engage PV interneuron-mediated inhibition differently.


Harm Reduction Strategies for Severe Alcohol Use Disorder in the Context of Homelessness: A Rapid Review.
Severe alcohol use disorder (AUD) in the context of housing instability remains one of the most complex health and social issues. Homelessness is related to increased vulnerability to stigma, marginalization and harmful ways of alcohol consumption, including non-beverage alcohol use (NBA). As a result, severe intoxication, alcohol poisoning, injury and death are common occurrences. Although harm minimization strategies have been readily proposed and examined in the context of drug use, applying the same principles to severe AUD remains controversial within the research and treatment community. This article summarizes the emerging research on managed alcohol programs to increase awareness about alcohol-related strategies that address severe AUD and provide other wrap-around supports such as housing, health and social services to mitigate various harms, including COVID-19.


Translational control of putative protooncogene Nm23-M2 by cytokines via phosphoinositide 3-kinase signaling.
The expansion and differentiation of hematopoietic progenitors is regulated by cytokine and growth factor signaling. To examine how signal transduction controls the gene expression program required for progenitor expansion, we screened ATLAS filters with polysome-associated mRNA derived from erythroid progenitors stimulated with erythropoietin and/or stem cell factor. The putative proto-oncogene nucleoside diphosphate kinase B (ndpk-B or nm23-M2) was identified as an erythropoietin and stem cell factor target gene. Factor-induced expression of nm23-M2 was regulated specifically at the level of polysome association by a phosphoinositide 3-kinase-dependent mechanism. Identification of the transcription initiation site revealed that nm23-M2 mRNA starts with a terminal oligopyrimidine sequence, which is known to render mRNA translation dependent on mitogenic factors. Recently, the nm23-M2 locus was identified as a common leukemia retrovirus integration site, suggesting that it plays a role in leukemia development. The expression of Nm23 from a retroviral vector in the absence of its 5'-untranslated region caused constitutive polysome association of nm23-M2. Polysome-association and protein expression of endogenous nm23-M2 declined during differentiation of erythroid progenitors, suggesting a role for Nm23-M2 in progenitor expansion. Taken together, nm23-m2 exemplifies that cytokine-dependent control of translation initiation is an important mechanism of gene expression regulation.


Physical losses could partially explain modest carotenoid retention in dried food products from biofortified cassava.
Gari, a fermented and dried semolina made from cassava, is one of the most common foods in West Africa. Recently introduced biofortified yellow cassava containing provitamin A carotenoids could help tackle vitamin A deficiency prevalent in those areas. However there are concerns because of the low retention of carotenoids during gari processing compared to other processes (e.g. boiling). The aim of the study was to assess the levels of true retention in trans-β-carotene during gari processing and investigate the causes of low retention. Influence of processing step, processor (3 commercial processors) and variety (TMS 01/1371; 01/1368 and 01/1412) were assessed. It was shown that low true retention (46% on average) during gari processing may be explained by not only chemical losses (i.e. due to roasting temperature) but also by physical losses (i.e. due to leaching of carotenoids in discarded liquids): true retention in the liquid lost from grating negatively correlated with true retention retained in the mash (R = -0.914). Moreover, true retention followed the same pattern as lost water at the different processing steps (i.e. for the commercial processors). Variety had a significant influence on true retention, carotenoid content, and trans-cis isomerisation but the processor type had little effect. It is the first time that the importance of physical carotenoid losses was demonstrated during processing of biofortified crops.


Human-Guided Modality Informativeness for Affective States.
This paper studies the hypothesis that not all modalities are always needed to predict affective states. We explore this hypothesis in the context of recognizing three affective states that have shown a relation to a future onset of depression: positive, aggressive, and dysphoric. In particular, we investigate three important modalities for face-to-face conversations: vision, language, and acoustic modality. We first perform a human study to better understand which subset of modalities people find informative, when recognizing three affective states. As a second contribution, we explore how these human annotations can guide automatic affect recognition systems to be more interpretable while not degrading their predictive performance. Our studies show that humans can reliably annotate modality informativeness. Further, we observe that guided models significantly improve interpretability, i.e., they attend to modalities similarly to how humans rate the modality informativeness, while at the same time showing a slight increase in predictive performance.


Asking a Great Question: A Librarian Teaches Questioning Skills to First-Year Medical Students.
In a single one-hour session, first-year medical students were taught a framework for differentiating between lower-order questions that lead to knowledge of facts and higher-order questions that lead to integration of concepts and deeper learning, thereby preparing them for problem-based learning (PBL). Students generated lists of questions in response to an assertion prompt and categorized them according to Bloom's Taxonomy. These data were analyzed in addition to data from the course exam, which asked them to formulate a higher-level question in response to a prompt. Categorizing questions according to Bloom's Taxonomy was a more difficult task for students than was formulating higher-order questions. Students reported that the skills that they learned were used in subsequent PBL sessions to formulate higher-order learning objectives that integrated new and previously-learned concepts.


Detection and analysis of different interactions between resistance mechanisms and carbapenems in clinical isolates of Klebsiella pneumoniae.
Carbapenems are considered last-line agents for the treatment of serious infections caused by Klebsiella pneumoniae, and this microorganism may exhibit resistance to β-lactam antibiotics due to different mechanisms of resistance. We evaluated 27 isolates of K. pneumoniae resistant to carbapenems recovered from inpatients at the University Hospital of Santa Maria-RS from July 2013 to August 2014. We carried out antimicrobial susceptibility, carbapenemase detection, testing for the presence of efflux pump by broth microdilution and loss of porin by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Genetic similarity was evaluated by ERIC-PCR. High levels of resistance were verified by the minimum inhibitory concentration for the antimicrobials tested. The blaKPC gene was present in 89% of the clinical isolates. Blue-Carba and combined disk with AFB tests showed 100% concordance, while the combined disk test with EDTA showed a high number of false-positives (48%) compared with the gold-standard genotypic test. Four isolates showed a phenotypic resistance profile consistent with the overexpression of the efflux pump, and all clinical isolates had lost one or both porins. The ERIC-PCR dendrogram demonstrated the presence of nine clusters. The main mechanism of resistance to carbapenems found in the assessed isolates was the presence of the blaKPC gene.


Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers.
To reduce the twin pregnancy rate, elective single embryo transfer (eSET) is increasingly implemented. Improvement of the results obtained with eSET can be achieved by better selection of the most viable embryo. This study investigated the predictive value of early cleavage (EC) as an additional parameter for selecting the embryo with the highest implantation potential by using data from SET's. Data from 165 SET's were retrospectively evaluated. Cleavage to the 2-cell stage was determined 23-26 h after injection or 25-28 h after insemination. Selection of the embryo to be transferred was based on cell morphology and cell number on the day of transfer, not on the EC status. Additional information on the predictive value of EC on developmental potential was obtained by analysing 253 transfers with two embryos (double embryo transfer, DET) and blastocyst formation of 1160 surplus embryos. Logistic regression was used to determine the predictors of pregnancy or blastocyst development. A significantly higher pregnancy rate was observed after transfer of single EC embryos compared to single non-EC embryos (46 versus 18%). This result was confirmed by the significantly higher pregnancy rate after DET with two EC embryos as compared to DET with two non-EC embryos (45 versus 25%) and the blastocyst formation of EC embryos compared to non-EC embryos (66 versus 40%). Logistic regression showed that EC is an independent predictor for both pregnancy and blastocyst development in addition to cell morphology and cell number. In order to improve the selection of the embryo with the highest implantation potential, selection for transfer should not be based on cell number and morphology on the day of transfer alone, but also on early cleavage status.


Metastasectomy for Stage IV Melanoma in the Era of Effective Systemic Agents.
There is an increasing body of literature that strongly suggests that complete metastasectomy for stage IV melanoma can improve overall survival. Before 2011, the efficacy of systemic therapy for melanoma was poor, making surgical resection the mainstay for treatment and the only realistic chance for cure. Now, in just a short time span (2011-2014), we have six Food & Drug Administration (FDA)-approved drugs for patients with stage IV metastatic melanoma. In the absence of prospective clinical trials evaluating the most advantageous sequence and timing for systemic therapy and surgical resection in the setting of stage IV melanoma, the treating surgical and medical oncologists must jointly devise individual treatment plans that take into account the advantages and disadvantages of each modality. This multidisciplinary approach gives the patient the best chance for prolonged survival. This article briefly reviews the FDA-approved systemic therapy options, discusses the data for site-specific metastasectomy, critiques the previous stage IV metastasectomy trials, and presents a view for moving forward with a multidisciplinary approach in mind.


Microfluidic-Based Nucleic Acid Amplification Systems in Microbiology.
Rapid, sensitive, and selective bacterial detection is a hot topic, because the progress in this research area has had a broad range of applications. Novel and innovative strategies for detection and identification of bacterial nucleic acids are important for practical applications. Microfluidics is an emerging technology that only requires small amounts of liquid samples. Microfluidic devices allow for rapid advances in microbiology, enabling access to methods of amplifying nucleic acid molecules and overcoming difficulties faced by conventional. In this review, we summarize the recent progress in microfluidics-based polymerase chain reaction devices for the detection of nucleic acid biomarkers. The paper also discusses the recent development of isothermal nucleic acid amplification and droplet-based microfluidics devices. We discuss recent microfluidic techniques for sample preparation prior to the amplification process.


Optimal and efficient generation of sine-Gordon breathers.
We investigate analytically and numerically whether an optimally designed defect structure can significantly reduce the threshold for breather train generation by almost two orders of magnitude in a sine-Gordon chain. By optimizing the parameters of defects based on a variational approach, we show that the decoupling of in-phase and antiphase branches allows us to independently minimize the driving threshold and reach the goal of emission of high-amplitude and well-formed breathers by an ultraweak driving. These results not only provide an optimal way for highly controllable and efficient emission of breathers, but also provide some insights into the mechanism of breather excitations in such processes as the DNA-protein interaction during transcription.


Hepcidin on 24-hour urine collection: preanalytical aspects and correlation with ferritin levels.
Urine hepcidin measurement is a potential non-invasive tool for assessing iron stores. However, hepcidin, due to its amphipathic structure, tends to aggregate and to adhere to surfaces in a protein-poor environment. In this study, we assessed the effect of solid bovine serum albumin (BSA) at different final concentrations (0, 2.5 or 5 g/L) in limiting the loss of hepcidin in spot urine samples. We also explored how hepcidin measured on plasma, spot or 24-hour urine collections can identify iron deficiency. Hepcidin levels were quantified on plasma, spot (with or without BSA) or 24-h urine collections for 33 volunteers. Hematological and iron status parameters were measured for each individual. The ability to detect iron deficiency (defined as a ferritin level <30 μg/L) based on plasma, spot or 24-h urine collections hepcidin levels was assessed by the means of receiver operator curves analysis. The addition of BSA into urine prior to sample collection prevented hepcidin loss by 13.3% (mean) in spot urine samples whatever the amount. The areas under the receiver operator curves obtained for detecting iron deficiency were respectively 0.94 and 0.93 for hepcidin levels obtained on plasma and 24-h urine collections. In this study, we showed that the addition of solid BSA into urine sample collection containers could prevent aggregation of hepcidin and that 24-h urine hepcidin levels could be as efficient as plasma concentrations for identifying iron deficiency.


Curaxin CBL0137 eradicates drug resistant cancer stem cells and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDA) continues to be one of the deadliest cancers due to the absence of effective treatment. Curaxins are a class of small molecules with anti-cancer activity demonstrated in different models of cancer in mice. The lead curaxin compound, CBL0137, recently entered Phase I clinical trials. Curaxins modulate several important signaling pathways involved in the pathogenesis of PDA through inhibition of chromatin remodeling complex FACT. FACT is overexpressed in multiple types of tumor, with one of the highest rate of overexpression in PDA (59%). In this study, the efficacy of CBL0137 alone or in combination with current standard of care, gemcitabine, was tested against different models of PDA in vitro and in mouse models. It was found that CBL0137 alone is a potent inducer of apoptosis in pancreatic cancer cell lines and is toxic not only for proliferating bulk tumor cells, but also for pancreatic cancer stem cells. In mice, CBL0137 was effective against several PDA models, including orthotopic gemcitabine resistant PANC-1 model and patient derived xenografts, in which CBL0137 anti-tumor effect correlated with overexpression of FACT. Moreover, we observed synergy of CBL0137 with gemcitabine which may be explained by the ability of CBL0137 to inhibit several transcriptional programs induced by gemcitabine, including NF-kappaB response and expression of ribonucleotide reductase, one of the targets of gemcitabine in cells. This data suggest testing of CBL0137 efficacy in Phase II trial in PDA patients alone and in combination with gemcitabine.


Early electrophysiological markers of atypical language processing in prematurely born infants.
Because nervous system development may be affected by prematurity, many prematurely born children present language or cognitive disorders at school age. The goal of this study is to investigate whether these impairments can be identified early in life using electrophysiological auditory event-related potentials (AERPs) and mismatch negativity (MMN). Brain responses to speech and non-speech stimuli were assessed in prematurely born children to identify early electrophysiological markers of language and cognitive impairments. Participants were 74 children (41 full-term, 33 preterm) aged 3, 12, and 36 months. Pre-attentional auditory responses (MMN and AERPs) were assessed using an oddball paradigm, with speech and non-speech stimuli presented in counterbalanced order between participants. Language and cognitive development were assessed using the Bayley Scale of Infant Development, Third Edition (BSID-III). Results show that preterms as young as 3 months old had delayed MMN response to speech stimuli compared to full-terms. A significant negative correlation was also found between MMN latency to speech sounds and the BSID-III expressive language subscale. However, no significant differences between full-terms and preterms were found for the MMN to non-speech stimuli, suggesting preserved pre-attentional auditory discrimination abilities in these children. Identification of early electrophysiological markers for delayed language development could facilitate timely interventions.


Survey of Aedes aegypti eggs in and around homes in Tucson, Arizona.
The abundance and location of eggs of Aedes aegypti were evaluated through inspection of 24 Tucson homes during the winter of 1998-99 to assess the potential of the mosquitoes to overwinter in this area. Eggs were found either indoors or outdoors in 46% of residences surveyed. After immersion in water, about 23% of eggs found indoors hatched, and about 5% of eggs found outdoors hatched.


A 28-kDa glycoprotein functions as a platelet ligand for P-selectin (CD62P).
P-selectin (CD62P) is expressed on activated platelets and on stimulated endothelial cells. It interacts with P-selectin glycoprotein ligand-1 (PSGL-1; CD162) for adhesion of activated platelets on leukocytes and for rolling of leukocytes on stimulated endothelial cells. Recently, resting and activated platelets have been shown to roll on endothelial P-selectin, indicating that platelets express (a) ligand(s) for P-selectin. Here we show that P-selectin specifically precipitated one 28-kDa glycoprotein from the whole cell lysates and the membrane lysates of human platelets in a Ca2+-dependent manner. Further, the purified 28-kDa molecule could inhibit the binding of P-selectin to human resting and activated platelets. In contrast, KPLI (a leukocyte adhesion blocking MoAb to PSGL-1) did not neutralize the binding of P-selectin to human platelets, even though it abolished the binding of P-selectin to human promyeloid HL-60 cells. Our results thus indicate that the 28-kDa glycoprotein may function as an important platelet ligand for P-selectin.


Dietary flavonoids-microbiota crosstalk in intestinal inflammation and carcinogenesis.
Colorectal cancer (CRC) is currently the third leading cancer and commonly develops from chronic intestinal inflammation. A strong association was found between gut microbiota and intestinal inflammation and carcinogenic risk. Flavonoids, which are abundant in vegetables and fruits, can inhibit inflammation, regulate gut microbiota, protect gut barrier integrity, and modulate immune cell function, thereby attenuating colitis and preventing carcinogenesis. Upon digestion, about 90% of flavonoids are transported to the colon without being absorbed in the small intestine. This phenomenon increases the abundance of beneficial bacteria and enhances the production of short-chain fatty acids. The gut microbe further metabolizes these flavonoids. Interestingly, some metabolites of flavonoids play crucial roles in anti-inflammation and anti-tumor effects. This review summarizes the modulatory effect of flavonoids on gut microbiota and their metabolism by intestinal microbe under disease conditions, including inflammatory bowel disease, colitis-associated cancer (CAC), and CRC. We focus on dietary flavonoids and microbial interactions in intestinal mucosal barriers as well as intestinal immune cells. Results provide novel insights to better understand the crosstalk between dietary flavonoids and gut microbiota and support the standpoint that dietary flavonoids prevent intestinal inflammation and carcinogenesis.


A microelectromechanical system (MEMS) capacitive accelerometer-based microphone with enhanced sensitivity for fully implantable hearing aid: a novel analytical approach.
The present work proposes a novel, compact, intuitively simple and efficient structure to improve the sensitivity of a microelectromechanical system (MEMS) capacitive accelerometer using an arrangement of microlever as a displacement amplifier. The accelerometer is proposed to serve as a microphone in the fully implantable cochlear prosthetic system which can be surgically implanted at the middle ear bone structure. Therefore, the design parameters such as size, weight and resonant frequency require deliberation. The paper presents a novel analytical model considering the impact of the mechanical amplification along with the width of the microlever and the capacitive fringe effects on the performance of the sensor. The design is simulated and verified using COMSOL MULTIPHYSICS 4.2. The accelerometer is designed within a sensing area of 1 mm2 and accomplishes a nominal capacitance of 4.85 pF and an excellent sensitivity of 5.91 fF/g.


Interactions between the sex of the clinician grader and the sex of the chiropractic student intern on spinal manipulation assessment grade.
The purpose of this project was to determine if there was any relationship between the sex of the clinician grader and the sex of the chiropractic student intern on student spinal manipulation assessment grades. Twelve thousand six hundred and thirty-one supervised patient adjustments by student interns were analyzed over a 3-year data collection window. Student interns were assessed by multiple male and female clinicians in a teaching clinic using a modified Dreyfus model scoring system on a 1-4 scale (1 = novice, 4 = proficient). A Mann-Whitney U test was used to compare the relationship between grader sex and student grade as well as student sex and student grade. Sex of the grader had a statistically significant effect on spinal manipulation assessment grade, p < .001, with male clinician graders assigning average scores of 2.81 ± 0.39 (mean ± SD) and female clinician graders scores of 3.01 ± 0.52, r = .18. Sex of the student had a statistically significant but negligible (r = .08) effect on spinal manipulation assessment grade, p < .001, with male students averaging slightly higher scores (2.93 ± 0.47) than females (2.86 ± 0.44) on the modified Dreyfus scale. Male clinicians tended to assign lower grades on spinal manipulation assessments than female clinicians. Male students on average received slightly higher scores than female students on spinal manipulation assessments.


Arterial Spin Labeling to Predict Brain Tumor Grading in Children: Correlations between Histopathologic Vascular Density and Perfusion MR Imaging.
Purpose To compare arterial spin labeling (ASL) data between low- and high-grade brain tumors in children to establish a cutoff to distinguish low- from high-grade neoplasms and to assess potential correlations between cerebral blood flow (CBF) and quantitative histologic microvascular data. Materials and Methods Approval was obtained from the regional review board. ASL data obtained in 129 children between 2011 and 2015 were retrospectively analyzed. CBF and relative CBF in the most perfused area of each neoplasm and contrast enhancement were quantified with a semiquantitative ratio. The correlation between CBF and microvascular density was analyzed in specimens stained with anti-CD34. Results were controlled in two validation cohorts with 1.5- and 3.0-T magnetic resonance (MR) imaging. Results Mean CBF was significantly higher for high-grade than for low-grade hemispheric (116 mL/min/100 g [interquartile range {IQR}, 73-131 mL/min/100 g] vs 29 mL/min/100 g [IQR, 23-35 29 mL/min/100 g], P < .001), thalamic (87 mL/min/100 g [IQR, 73-100 mL/min/100 g] vs 36 mL/min/100 g [IQR, 30-40 mL/min/100 g], P = .016), and posterior fossa (59 mL/min/100 g [IQR, 45-91 mL/min/100 g] vs 33 mL/min/100 g [IQR, 25-40 mL/min/100 g], P < .001) tumors. With a cutoff of 50 mL/min/100 g, sensitivity and specificity were 90% (95% confidence interval [CI]: 68, 100) and 93% (95% CI: 66, 100), respectively, for hemispheric tumors; 100% (95% CI: 48, 100) and 80% (95% CI: 28, 100), respectively, for thalamic tumors; and 65% (95% CI: 51, 78) and 94% (95% CI: 80, 99), respectively, for posterior fossa tumors. In posterior fossa tumors, additional use of the CBF-to-contrast enhancement ratio yielded sensitivity and specificity of 96% (95% CI: 87, 100) and 97% (95% CI: 84, 100), respectively. Use of a simple algorithm based on these values yielded an accuracy of 93% (95% CI: 87, 97). Validation sets yielded similar results, with grading accuracy of 88% (95% CI: 62, 98) with 1.5-T MR imaging and 77% (95% CI: 46, 95) with 3.0-T MR imaging. CBF was strongly correlated with microvascular density (R = 0.66, P < .001). Conclusion High-grade pediatric brain tumors display higher CBF than do low-grade tumors, and they may be accurately graded by using these values. CBF is correlated with tumor microvascular density. © RSNA, 2016 Online supplemental material is available for this article.


Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML.
Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations-Del (5q), T (15; 17), T (9; 22), and T (9; 11)-are significantly associated with patient survival. Del (5q)-positive patients have an average survival of less than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.


Contamination of embryo transfer catheter and treatment outcome in in vitro fertilization.
The effect of embryo transfer (ET) catheter contamination with mucus and/or blood on treatment outcome in an in vitro fertilization (IVF) program was evaluated. One thousand four ET procedures in 877 patients having conventional IVF in the long (1189 cycle) and short (15 cycles) protocol were analyzed to determine the impact of catheter contamination on the incidence of retained embryos and the clinical pregnancy rate. Catheter contamination with mucus and/or blood is a feature of difficult ET. Embryos were significantly more likely to be retained when the transfer catheter was contaminated with mucus (17.8 versus 3.3%) or blood (12 versus 3.3%). When the catheter was contaminated and an embryo(s) was retained and immediately retransferred, the pregnancy rate was not compromised. The pregnancy rate was significantly reduced when the ET catheter was contaminated with blood (15.5 versus 27.1%; P = 0.002), but no embryo was retained in the catheter set. Catheter contamination compromises the treatment outcome in IVF only when there is no associated retained embryo(s). As increased vigilance in searching for extruded embryos may not be practical, we suggest that cervical mucus should be routinely aspirated and ET performed as atraumatically as possible.


Coronary vasospastic crisis leading to cardiogenic shock and recurrent ventricular fibrillation in a patient with long-standing asthma.
Acute myocardial infarction in patients with normal coronary arteries is a therapeutic dilemma. Coronary artery vasospasm and thrombosis are the most commonly encountered clinic problems and appear in localized coronary segments. The incidence of cardiovascular disease is increased in asthmatic patients. ß(2)-Adrenergic agonists use is associated with increased cardiovascular events. Although myocardial ischemia during asthma has been described in literature, acute myocardial infarction and ventricular fibrillation with normal coronary arteries in patients with asthma bronchiale is a rare entity. Our patient with long-standing asthma bronchiale presented with cardiogenic shock whose coronary angiography revealed multivessel disease and undergone primary percutaneous coronary intervention. Due to ongoing chest pain and hemodynamic instability; an early bypass surgery was planned. A control angiogram was performed before surgery. After intracoronary nitrate administration all narrowings in coronary vasculature disappeared. Symptom relief and clinical improvement was achieved with nitrate and calcium channel blockers later. After 2 months she was readmitted with cardiac arrest due to recurrent ventricular fibrillation and intracardiac defibrillator implantation was performed.


Hydrocephalus and primary ciliary dyskinesia.
Primary ciliary dyskinesia was shown in a 12 year old boy with bronchiectasis who had developed hydrocephalus in the neonatal period. The possible relevance of his ciliary abnormality is discussed.


Development of oxidised and heat-moisture treated potato starch film.
This study investigated the effects of sodium hypochlorite oxidation and a heat-moisture treatment of potato starch on the physicochemical, pasting and textural properties of potato starches in addition to the water vapour permeability (WVP) and mechanical properties of potato starch films produced from these starches. The carbonyl contents, carboxyl contents, swelling power, solubility, pasting properties and gel texture of the native, oxidised and heat-moisture treated (HMT) starches were evaluated. The films made of native, oxidised and HMT starches were characterised by thickness, water solubility, colour, opacity, mechanical properties and WVP. The oxidised and HMT starches had lower viscosity and swelling power compared to the native starch. The films produced from oxidised potato starch had decreased solubility, elongation and WVP values in addition to increased tensile strength compared to the native starch films. The HMT starch increased the tensile strength and WVP of the starch films compared to the native starch.


Conceptualizing child sexual abuse in interpersonal context: recovery of people, not memories.
The controversy regarding delayed recall of childhood sexual abuse (CSA) has deflected> attention from the question of whether memory recovery and other trauma-focused treatment approaches are effective for abuse survivors. More than a decade of clinical experience has convinced many experts that as a primary treatment strategy, this approach often leads to decompensation among CSA survivors. However, few treatment alternatives have been clearly articulated. One such alternative, contextual therapy, is grounded in evidence that many CSA survivors grow up in an interpersonal context that fails to transmit the capacities needed for effective daily functioning. Contextual therapy retains trauma-focused interventions as one component of a broader framework aimed at helping survivors develop adaptive capacities that, rather than having been disrupted by trauma, may never have been attained in the first place. From this perspective, abuse trauma is seen as compounding these deficits, rather than as a sole cause of them.


Acute combined posterior cruciate and posterolateral instability of the knee.
This report concerns 13 consecutive patients (13 knees) who underwent operative treatment for acute combined posterior cruciate and posterolateral instability due to combined injury to the posterior cruciate ligament and the arcuate ligament complex. Our purpose was to examine the method of diagnosis and the results in these patients. There were 12 males and 1 female (average age, 26 years). Five patients were injured in a motor vehicle accident, four in sports activities, and four in nonsports activities. The mechanism of injury was an anteromedial blow to the flexed knee in six patients, a fall onto the knee in two, and unknown in five patients. Eleven patients were available for follow-up evaluation (average, 56 months), and in each the result was rated as good, fair, or poor. In 10 patients (90%) the results were rated as good subjectively, in 11 (100%) as good functionally, and in 8 (73%) as good objectively. Injury to both the posterior cruciate ligament and the arcuate ligament complex can result from rotational force that can be due to a blow to the anteromedial aspect of the knee. Diagnosis can be made by a combined positive response to the posterior drawer test, the anterior drawer test performed with the tibia in internal rotation, the abduction and adduction stress tests performed with the knee in full extension, the posterolateral drawer test, and the external rotation-recurvatum test. In a knee with concomitant injury to the posterior cruciate ligament and the arcuate ligament complex that requires surgical repair, all injured structures should be explored and repaired to ensure a subjectively, objectively, and functionally good result.


Pain and breastfeeding: a prospective observational study.
To demonstrate that pain affects the goodness of breastfeeding. Seventy-nine patients were interviewed regarding satisfaction in breastfeeding, tiredness, uterine pain, nipple and other pain, and analgesic use at day three and at first, second, third, and fourth week after birth. Data regarding the mode of delivery were recorded from medical charts. Milk formula supplements, bottle use, pacifier use, and nipple shields use were considered as variables suggesting unsuccessful breastfeeding. At third day after delivery, it appeared that analgesic use was significantly associated with milk formula supplementing, bottle use, less satisfaction in breastfeeding, and more tiredness. At first week after delivery, the presence of pain differing from nipple and uterine pain, was more likely associated with milk formula supplementing, bottle use, pacifier use, less satisfaction in breastfeeding, and more tiredness. At third week after delivery, nipple pain was directly related to tiredness, while it increased the odds of adding milk formula and using a bottle. Pain affects the goodness of breastfeeding.


Long-term survivors of HIV infection.
The persistent immune competence seen in a small percentage of HIV-infected individuals reflects the heterogeneity of both the virus and the host. Some HIV strains, for example, are more cytopathic than others. Host factors that promote longer survival lack "enhancing" antibodies, an appropriate balance of two crucial CD4+ cell subsets and their cytokines, and a strong CD8+ cell antiviral response.


Can adolescents' subjective wellbeing facilitate their pro-environmental consumption behaviors? Empirical study based on 15-year-old students.
To address the challenge of declining pro-environmental behaviors in adolescence, this paper uses the theoretical foundations for subjective wellbeing to verify the influence of three latent dimensions of subjective wellbeing (life satisfaction, positive emotions, and negative emotions) on adolescents' pro-environmental consumption behaviors (PECBs). Furthermore, we explore the moderating effects of nations and regions in the relationship between subjective wellbeing and PECBs in adolescents. Based on the international data from the Programme for International Student Assessment 2018 (PISA 2018), we construct a unique dataset that includes 57,182 samples related to the subjective wellbeing and PECBs of 15-year-old students from eight countries/economies. Specially, we employ an ordered probit model to test our hypotheses. Both adolescents' life satisfaction and positive emotions can significantly improve their PECBs, while there is a significant negative association between negative emotions and PECBs. At the nation's level, adolescents' life satisfaction and negative emotions in developed countries/economies significantly impact PECBs. In contrast, the positive emotions of adolescents in developing countries/economies have more substantial effects on PECBs. At the regional level, the impact of all three dimensions of adolescents' subjective wellbeing on PECBs is more significant in rural than urban areas. This paper provides a new perspective for understanding adolescents' PECBs from the insights of subjective wellbeing. Previous studies have examined the effects of life satisfaction or happiness on PECBs in adults. This paper examines the impact of subjective wellbeing on adolescents' PECBs from life satisfaction, positive emotions, and negative emotions, which suggests that promoting adolescents' subjective wellbeing can be an effective strategy for encouraging PECBs. From a comparative research perspective, we further analyze the differences between the nations at different levels of development, the rural and urban areas, providing a valuable reference for policymakers and practitioners in promoting pro-environmental behaviors among adolescents.


Identification of SARS-COV spike protein-derived and HLA-A2-restricted human CTL epitopes by using a new muramyl dipeptidederivative adjuvant.
Severe acute respiratory syndrome (SARS) spread during the winter of 2003, and attempts have been made to develop vaccines against SARS corona virus (SARS-CoV). The present study provides a strategy to rapidly identify SARS-CoV-derived antigenic peptides recognized by HLA-A2-restricted cytotoxic T lymphocytes (CTLs). Forty-three candidate peptides having HLA-A2-binding motifs were selected in silico and HLA-A2/Db chimeric MHC class I-transgenic mice were immunized with these peptides and a new derivative of muramyl dipeptide that can induce upregulation of HLA-DR, CD80, CD86, and CD40 in human CD14+ antigen presenting cells, was administered as an adjuvant. Six HLAA2-restricted mouse CTL epitopes were identified, including two new epitopes which have never been reported before. One of the novel peptides was naturally processed and successfully induced HLAA2-restricted specific CTLs in both HLA transgenic mice and healthy donors. The method was useful, convenient and efficient for rapid identification of CTL epitopes derived from SARS-CoV proteins and will be possibly applicable for other pathogens to develop a peptide-based vaccine.


The relationship between Dietary Inflammatory Index and disease severity and inflammatory status: a case-control study of COVID-19 patients.
Numerous studies have revealed strong relationships between COVID-19 and inflammation. However, the imminent link between diet-related inflammation and the COVID-19 risk has not been addressed before. So, we explored the capability of the Energy-Adjusted Dietary Inflammatory Index (E-DII) to predict the inflammatory markers, incidence and severity of COVID-19. We conducted a case-control study consisting of 120 adults; they had been admitted for COVID-19 at hospital during June and July, 2020. The E-DII score was calculated based on the dietary intake, which was evaluated by a 138-item semi-quantitative food frequency questionnaire. Serum levels of inflammatory markers including the Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and White blood cells (WBCs) differential were measured. Severity of disease was assessed by chest radiology criteria. Patients with the maximum pro-inflammatory energy adjusted E-DII score had 7·26 times greater odds of developing COVID-19, as compared to those in tertiles 1 (E-DII T3v. E-DII T1: OR = 7·26; 95 % CI 2·64 to 9·94, P < 0·001). Also, a positive association between E-DII and C-reactive protein (CRP) was observed (BE-DII = 1·37, 95 % CI 0·72, 2·02), such that with each unit increase in E-E-DII, the CRP levels were increased by 1·37 units. Furthermore, a significant association was found between E-DII and the severity of disease (BE-DII = 0·03, 95 % CI 0·01, 0·06. 0·024). Patients consuming a diet with a higher pro-inflammatory potential were at a greater risk of COVID-19 occurrence; also, the severity of disease was elevated with a high score inflammatory diet.


Retroperitoneoscopic laparoscopic distal pancreatectomy with spleen salvage.
Laparoscopic pancreatic surgery has now developed as a clinical practice. In urological surgery, direct extraperitoneal surgery has become popular in laparoscopic adrenalectomy and nephrectomy. As the pancreas is also an organ located in the retroperitoneal cavity, we evaluate the efficacy of retroperitoneoscopic laparoscopic distal pancreatectomy. Specific-pathogen-free Large Yorkshire pigs were studied. No major bleeding episodes were encountered. After carbon dioxide insufflation, the abdominal viscera were inspected with a laparoscope. Below the left costal convexity, the balloon dissector was introduced and the second port was inserted in the retroperitoneal cavity. The scope was inserted using that port and additional two ports were inserted into the retroperitoneal cavity. The tail to body of the pancreas were easily mobilized from the retroperitoneum. The identified splenic artery and vein were carefully isolated from the pancreas. After lap-disk was applied to a 4-cm incision, the tail of the pancreas was pulled out to resect using various devices. The cut surface of the pancreas resected with ultrasonic dissector showed a less damaged area than that with monopolar electrocautery and bipolar electrocautery. Retroperitoneoscopic laparoscopic distal pancreatectomy is a rational procedure and is safe. As the pancreatic parenchyma has greater water content, the devices of ultrasonic dissector seem to be helpful.


Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.
Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.


Prevalence of toxoplasma antibodies in blood donors and pregnant women in Khon Kaen Province.
Serum samples from blood donors and pregnant women in Khon Kaen were examined for antibodies to Toxoplasma by an indirect hemagglutination and indirect fluorescent antibody techniques. It was found that 6.4 per cent of the blood donors were positive by the indirect hemagglutination and 6.2 per cent by indirect fluorescent antibody tests. The seroprevalence in pregnant women were 12.0 per cent by indirect hemagglutination and 4.7 per cent by indirect fluorescent antibody tests. The frequency distribution curves of indirect hemagglutination titers were unimodal in both the groups studied. From the basis of these findings, it was concluded that toxoplasmosis is not endemic in Khon Kaen and the transmission occurs at a very low level.


The effect of alcohol on the vestibulo-ocular reflex and apparent concomitant motion.
Measures of the vestibulo-ocular reflex (VOR) and apparent concomitant motion (ACM), the apparent motion of stationary visual stimuli during head motion, were obtained during sessions in which subjects consumed either alcoholic or placebo beverages. Both VOR and ACM remained constant throughout the placebo sessions. During sessions in which alcohol was consumed, the gain of the VOR was reduced and there was an increased tendency to see ACM in the direction opposite head motion. The effects of alcohol on ACM were greatest 50 min following cessation of drinking, near the maximum of the blood alcohol concentration (BAC). ACM measures then returned towards baseline, whereas the BAC measures remained elevated. VOR gain alterations paralleled the BAC measures. Therefore, reduction of VOR gain with alcohol produces an increase of ACM, but the ACM changes are relatively transient when compared with the altered VOR gain.


Treating Low-Grade Myxofibrosarcoma With Stereotactic Body Radiation Therapy Using CyberKnife®.
Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas. Low-grade MFS has a high local recurrence rate, similar to that of high-grade MFS. Hence, appropriate adjuvant therapy is required to control low-grade MFS. In this report, we present a case in which recurrent low-grade MFS was successfully treated with stereotactic body radiation therapy (SBRT) using CyberKnife® (CK) (Accuray Incorporated, Sunnyvale, CA). A 76-year-old man underwent SBRT using CK for recurrent low-grade MFS in the right posterior chest wall after undergoing resection and skin grafting four and three times, respectively. We planned CK treatment separately for each in two parts. For the lesion on the scapula side, the target volume was 109 cm3 and the total prescribed dose was 34.6 Gy, while the lesion on the spinal side had a target volume of 72 cm3 and a total prescribed dose of 36 Gy, both in five fractions. Each SBRT was performed on alternate days in a span of 14 days. The tumors gradually reduced in size with tolerable levels of toxicity. SBRT using CK could be a safe and effective adjuvant therapy for low-grade MFS.


"As Natural as the Air Around Us": On the Origin and Development of the Concept of Structural Violence in Health Research.
This article examines the concept of "structural violence." Originating in the work of Johan Galtung in 1969 and popularized by Paul Farmer, structural violence is increasingly invoked in health literature. It is a complex concept - rich in its explanatory potential but vague in its operational definition and arguably limited in its theoretical precision. Its potential lies in the focus it gives to the deep structural roots of health inequities; in contrast to the more passive term "social determinants of health," structural violence explicitly identifies social, economic, and political systems as the causes of the causes of poor health. It is also evocative in its framing of health inequities as an act of violence. Yet the formulation of structure used in this literature is largely atheoretical and, by extension, apolitical. Development of the concept hinges on clarifying the precise aspects of structure it points to (perhaps through using the concept in conjunction with larger theoretical frameworks) as well as improving operational definitions to enable its use in quantitative social epidemiology. We argue that the concept of structural violence can provide a useful lens for understanding health inequities, but its full potential is only realized when combined with larger theoretical frameworks.


Maturation of fetal human neural xenografts in the adult rat brain.
Transplantation of human fetal neural cells has been used for several years as a treatment for Parkinson's disease. These therapeutic trials were based on a large number of rat allografts studies, and the species to species extrapolation appeared valid in many respects. One major difference between neurons of various species, however, is their rate of maturation; indeed, human neurons have been proven to grow much more slowly than rat neurons. This has been studied mostly, up to now, at the light microscope level. In an attempt to determine the fine structural correlates of this protracted development and to detail the schedule of morphogenesis and synaptogenesis, human fetal brain stem tissue (at 8 weeks of gestation) was transplanted into a previously lesioned brain area of immunosuppressed adult rats. Transplants, which were allowed to develop for 15 days to 3 months, were analyzed using the electron microscope. At 15 days, small cells containing a large nucleus were surrounded by wide extracellular spaces. At 1 month, grafted neurons displayed a thin rim of cytoplasm and few thin processes. At 2 months, extracellular spaces tended to diminish. Thin processes formed bundles and large processes extended from enlarged neurons. Major changes were observed at 3 months survival as the neuropile filled up with cells and processes and synaptogenesis began. Comparison with a similar ultrastructural study of thalamic rat allografts shows that human cells develop following a pattern similar to that in rat cells but that the duration of each maturation step is largely extended.


Circulating Levels of Leptin and Lipocalin-2 in Patients With X-Linked Hypophosphatemia.
Individuals with X-linked hypophosphatemia (XLH) are at greater risk for being overweight or obese. Whether there are underlying metabolic abnormalities that put patients with XLH at greater risk for excessive weight gain is largely unknown. Lipocalin-2 (LCN2) has recently received attention as a factor regulating energy consumption and specifically is postulated to be anorexigenic and to improve insulin sensitivity. In a retrospective study, circulating levels of LCN2, leptin, and insulin were measured in 32 patients with XLH, ages 2-60 years, all of whom were being treated with burosumab, and 38 control subjects. Control subjects were chosen who were close in age to those with XLH, with a similar number of participants of each sex. Subjects were analyzed in 3 age cohorts, 2-10 years, 11-18 years, and 20-60 years. In all age groups LCN2 levels were lower in the patients with XLH than in controls but when adjusted for weight class (normal, overweight, obese) the differences were not significant. In contrast, serum leptin levels were significantly lower in children with XLH compared to controls in the 2-10 years age cohort. Serum levels of insulin were also significantly lower in the 2-10-year-old children with XLH when compared with controls. We conclude that changes in expression of lipocalin-2 in children and adolescents with XLH is unlikely to contribute to their risk for obesity in adulthood. It is unclear if lower circulating levels of leptin in these children plays a role in the higher prevalence of obesity among adults with XLH.


Ketamine: synaptogenesis, immunomodulation and glycogen synthase kinase-3 as underlying mechanisms of its antidepressant properties.
Major depressive disorder is an extremely debilitating condition affecting millions of people worldwide. Nevertheless, currently available antidepressant medications still have important limitations, such as a low response rate and a time lag for treatment response that represent a significant problem when dealing with individuals who are vulnerable and prone to self-harm. Recent clinical trials have shown that the N-methyl-D-aspartate receptor antagonist, ketamine, can induce an antidepressant response within hours, which lasts up to 2 weeks, and is effective even in treatment-resistant patients. Nonetheless, its use is limited due to its psychotomimetic and addictive properties. Understanding the molecular pathways through which ketamine exerts its antidepressant effects would help in the developing of novel antidepressant agents that do not evoke the same negative side effects of this drug. This review focuses specifically on the effects of ketamine on three molecular mechanisms that are relevant to depression: synaptogenesis, immunomodulation and regulation of glycogen synthase kinase-3 activity.


Structural requirements for delta opioid receptor binding.
Structural features influencing opioid activity of enkephalin analogs were investigated through the synthesis and evaluation of opioid receptor binding affinities of a series of cyclic dithioether-containing analogs and structurally related linear analogs of the cyclic, disulfide-containing peptides, [D-Pen2, D-Pen5]enkephalin and [D-Pen2, L-Pen5]enkephalin, where Pen (penicillamine) is beta, beta-dimethylcysteine. The major effect of increasing the ring size of the cyclic moiety from disulfide to dithioether analogs was a large decrease in delta opioid receptor binding affinity which suggests that relatively compact conformations of the peptide ligand are necessary for optimal binding to this receptor. The effect of bulky, hydrophobic residues at position 2 in the peptide chain was evaluated by preparing the linear analogs, [D-t-Leu2, D-t-Leu5]enkephalin (t-Leu, 2-amino-3,3-dimethylbutanoic acid) and [D-Abu2, D-t-Leu5]enkephalin (Abu, 2-aminobutanoic acid). The former analog was found to be 36- and 450-fold less potent at delta and mu receptor sites, respectively, than was the latter, suggesting that bulky side chain substituents in position 2 of enkephalin analogs lead to a deleterious steric interaction at delta and particularly at mu receptors.


Filoviruses: Scientific Gaps and Prototype Pathogen Recommendation.
Viruses in the family Filoviridae, including the commonly known Ebola (EBOV) and Marburg (MARV) viruses, can cause severe hemorrhagic fever in humans and nonhuman primates. Sporadic outbreaks of filovirus disease occur in sub-Saharan Africa with reported case fatality rates ranging from 25% to 90%. The high mortality and increasing frequency and magnitude of recent outbreaks along with the increased potential for spread from rural to urban areas highlight the importance of pandemic preparedness for these viruses. Despite their designation as high-priority pathogens, numerous scientific gaps exist in critical areas. In this review, these gaps and an assessment of potential prototype pathogen candidates are presented for this important virus family.


Diagnostic Blood Biomarkers for Acute Pulmonary Embolism: A Systematic Review.
(1) Background: The current diagnostic algorithm for acute pulmonary embolism (PE) is associated with the overuse of CT pulmonary angiography (CTPA). An additional highly specific blood test could potentially lower the proportion of patients with suspected PE that require CTPA. The aim was to summarize the literature on the diagnostic performance of biomarkers of patients admitted to an emergency department with suspected acute PE. (2) Methods: Medline and Embase databases were searched from 1995 to the present. The study selection process, data extraction, and risk of bias assessment were conducted by two reviewers. Eligibility criteria accepted all blood biomarkers except D-dimer, and CTPA was used as the reference standard. Qualitative data synthesis was performed. (3) Results: Of the 8448 identified records, only 6 were included. Eight blood biomarkers were identified, of which, three were investigated in two separate studies. Red distribution width and mean platelet volume were reported to have a specificity of ≥ 90% in one study, although these findings were not confirmed by other studies. The majority of the studies contained a high risk of selection bias. (4) Conclusions: The modest findings and the uncertain validity of the included studies suggest that none of the biomarkers identified in this systematic review have the potential to improve the current diagnostic algorithm for acute PE by reducing the overuse of CTPA.


5-HTTLPR and anxiety modulate brain-heart covariation.
To date, little is known about genes affecting the interplay of brain and heart activity. Because serotonin (5-HT) is involved in corticovagal neurotransmission, we tested whether the 5-HT transporter polymorphism 5-HTTLPR affects brain-heart covariation. Further, associations with neuroticism/anxiety (NANX) were tested, as anxiety is related to 5-HT and neurogenic changes of heart period (HP). N = 168 participants performed a time-estimation task while EEG and HP were recorded. Brain-heart covariation was measured using time-lagged within-subject correlations of centromedial feedback-evoked single-trial EEG at 300 ms and subsequent changes of HP. EEG-HP correlations were higher in 5-HTTLPR long allele carriers. Moreover, after negative feedback, EEG-HP correlations and feedback-related negativity amplitudes independently correlated with NANX. The results indicate that individual differences in brain-heart covariation relate to 5-HT and NANX.


Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response.
Early in the COVID-19 pandemic, data suggested that males had a higher risk of developing severe disease and that androgen deprivation therapy might be associated with protection. Combined with the fact that TMPRSS2 (transmembrane serine protease 2), a host entry factor for the SARS-CoV-2 virus, was a well-known androgen-regulated gene, this led to an upsurge of research investigating androgen receptor (AR)-targeting drugs. Proxalutamide, an AR antagonist, was shown in initial clinical studies to benefit COVID-19 patients; however, further validation is needed as one study was retracted. Due to continued interest in proxalutamide, which is in phase 3 trials, we examined its ability to impact SARS-CoV-2 infection and downstream inflammatory responses. Proxalutamide exerted similar effects as enzalutamide, an AR antagonist prescribed for advanced prostate cancer, in decreasing AR signaling and expression of TMPRSS2 and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. However, proxalutamide led to degradation of AR protein, which was not observed with enzalutamide. Proxalutamide inhibited SARS-CoV-2 infection with an IC50 value of 97 nM, compared to 281 nM for enzalutamide. Importantly, proxalutamide inhibited infection by multiple SARS-CoV-2 variants and synergized with remdesivir. Proxalutamide protected against cell death in response to tumor necrosis factor alpha and interferon gamma, and overall survival of mice was increased with proxalutamide treatment prior to cytokine exposure. Mechanistically, we found that proxalutamide increased levels of NRF2, an essential transcription factor that mediates antioxidant responses, and decreased lung inflammation. These data provide compelling evidence that proxalutamide can prevent SARS-CoV-2 infection and cytokine-induced lung damage, suggesting that promising clinical data may emerge from ongoing phase 3 trials.


Habitat difference in abundance of willow leaf beetle Phratora vulgatissima (Coleoptera: Chrysomelidae): plant quality or natural enemies?
Herbivorous insects are influenced by both 'bottom-up' forces mediated through host plants and 'top-down' forces from natural enemies. Few studies have tried to evaluate the relative importance of the two forces in determining the abundance of insects. The leaf beetle Phratora vulgatissima Linnaeus sometimes occurs at high densities and severely damages the willow Salix cinerea in forest habitats. For willows growing in open agricultural landscapes (farmland S. cinerea), the leaf beetle generally occurs at low densities and plants receive little damage. The purpose of the present study was to evaluate the relative importance of host plant quality and natural enemies behind the observed difference in P. vulgatissima abundance. Female egg-laying and larval performance (growth and survival) were studied on caged willow branches in the field to investigate if plant quality differs between S. cinerea trees growing in forest and farmland habitats. The survival of eggs exposed to natural enemies was examined to see if predation could explain the low abundance of leaf beetles on farmland willows. The results indicated no difference in plant quality; female egg laying and larval performance did not differ between the forest and the farmland. However, heteropteran predators (true bugs) were more abundant, and the survival of eggs was lower, on plants in the farmland habitat than in the forest habitat. The data suggest that the low abundance of P. vulgatissima on farmland willows could not be explained by a poor quality of plants, but more likely by high predation from heteropterans.


Fuc(alpha1-->3)GalNAc-: the major antigenic motif of Schistosoma mansoni glycolipids implicated in infection sera and keyhole-limpet haemocyanin cross-reactivity.
The aim of the present study was the characterization of the dominant epitope present on Schistosoma mansoni glycolipids, which causes cross-reactivity of S. mansoni and S. haematobium infection sera with keyhole-limpet haemocyanin (KLH). To this end, the monoclonal antibody M2D3H was chosen for its similar behaviour in high-performance TLC immunostaining and inhibition-ELISA to infection sera. Individual, structurally defined oligosaccharides derived from S. mansoni egg glycolipids were tested for their binding to this monoclonal antibody by immunoaffinity chromatography. A terminal fucose residue linked in the (alpha1-->3) position to N-acetylgalactosamine was found to be the common structural determinant of the four oligosaccharides binding to M2D3H. The Fuc(alpha1-->3)GalNAc-motif also appeared to be the basis for the cross-reactivity with KLH, a phenomenon used in the serodiagnosis of S. mansoni, S. haematobium and S. japonicum infections.


One-Pot Syntesis of 3-Functionalized 4-Hydroxycoumarin under Catalyst-Free Conditions.
A concise and efficient one-pot synthesis of 3-functionalized 4-hydroxycoumarin derivatives via a three-component domino reaction of 4-hydroxycoumarin, phenylglyoxal and 3-arylaminocyclopent-2-enone or 4-arylaminofuran-2(5H)-one under catalyst-free and microwave irradiation conditions is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.


Glucagon for the relief of esophageal food impaction does it really work?
We sought to evaluate our experience with glucagon used in the emergency department setting to relieve esophageal food impaction (EFI). We reviewed the records of patients with food impaction who received glucagon between January 1998 and May 2003 and recorded patient demographics, medical history, symptoms following glucagon administration, and endoscopic findings. There were 92 episodes of food impaction in 85 patients. Thirty-three percent of the episodes resulted in resolution of symptoms following a dose of glucagon. Sixty-seven percent had symptoms of food impaction after glucagon and underwent upper endoscopy in the emergency room. Only previous solid food dysphagia was positively associated with response to glucagon. Patients who received glucagon plus a benzodiazepine were more likely to have resolution of the EFI. In our experience, glucagon appears to relieve food impaction in one third of patients treated. This result is comparable to previously published data examining glucagon and placebo. The lack of advantage over placebo questions the practice of glucagon administration for EFI.


Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt-Jakob disease patients.
A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPres. PrPres derives from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methionine or valine residue at the polymorphic position 129 may be critical in sporadic CJD cases. We found that in the brain of patients heterozygous for the mutation in which isoleucine is substituted for valine at codon 210 (Val21Olle), the PrPres is formed by both the wild-type and mutant PrPsen. We also found that in a sporadic CJD patient, who was heterozygous (Met/Val) at position 129, PrPres is also formed by both allotypes. These data associate transmissible spongiform encephalopathies with other amyloidosis, although the nature of the transmissible agent remains unsettled.


Surgery for young onset diverticulitis: is it curative?
Previously considered a disease of old age, diverticular disease is increasingly prevalent in younger populations. Guidelines on surgical resection have shifted from recommending resection for all young onset patients to an individualized approach. Therefore, we aim to determine demographics and outcomes including radiographic and surgical recurrence rates in patients < 40 years old undergoing resection for diverticular disease. A retrospective, single center study was performed. All patients ≤ 39 years undergoing operative intervention for left-sided diverticular disease between Jan 2010 and July 2017 were included. Recurrence was determined by individual review of imaging and operative reports. Overall, 147 (n = 107/72.8% male, mean age = 34.93 ± 4.12 years) patients were included. The majority were ASA 1 or 2 (n = 41/27.9% and n = 82/55.8%). The most common surgical indication was uncomplicated diverticulitis (n = 77, 52.4%) followed by perforation (n = 26/17.7%). The majority (n = 108/73.5%) of cases were elective. Seventy-nine (57.3%) of all cases were performed laparoscopically. Primary anastomosis without diversion was the most common surgical outcome (n = 108/73.5%). Median length of stay was 5 (4, 7) days. There was no mortality. There were three (2.0%) intraoperative and 38 (25.9%) postoperative complications. The most common complication was anastomotic leak (n = 6/4.1%). The majority (n = 5) of leaks occurred after elective surgery. Two neoplastic lesions (1.3% of cohort) were found (1 adenoma with low-grade dysplasia/1 polyp cancer). Over a mean follow-up of 96 (74, 123) months, only 2 (1.3%) patients experienced a surgical or radiological recurrence. Both neoplasia and recurrence after resection for diverticular disease in young onset patients are rare. Leaks after primary anastomosis even in the elective setting warrant careful consideration of a defunctioning ileostomy.


Rupture of a myomectomy site in the third trimester of pregnancy after myomectomy, septoplasty and cesarean section: A case report.
Uterine rupture during pregnancy is a rare but dangerous complication. A history of cesarean section is known to be a risk factor, but other types of uterine surgery can also increase the risk. We report a case of rupture of a myomectomy site in the third trimester of pregnancy without uterine contractions in a woman who had previously undergone myomectomy, septoplasty and cesarean section. The 39-year-old woman (gravida 2, para 2) presented at 29 weeks' gestation with uterine contractions. She was successfully treated with tocolytics. At 32 weeks of pregnancy, in the absence of contractions, the patient complained of severe abdominal pain and she became hypotensive. Emergency laparotomy and cesarean section were performed, resulting in the delivery of a live infant. The myomectomy site was found to have ruptured but the cesarean and septoplasty scars were intact. This case suggests that myomectomy scars are at greater risk of rupture during pregnancy than those resulting from cesarean section and septoplasty.