Office Cervicoscopy versus Stationary Colposcopy in Suspicious Cervix: A Randomized Controlled Trial.
The objective of the study was to estimate the diagnostic accuracy and doctor satisfaction of small caliber office cervicoscopy versus stationary colposcopy in diagnosis of ectocervical as well as endocervical lesions in women clinically presented with suspicious cervix. Eligible 112 cases with clinically suspicious cervix were randomized into Group A (56 cases) and Group B (56 cases) who were subjected to small caliber office cervicoscopy and stationary colposcopy, respectively. The outcome was the diagnostic accuracy and safety of both tools for detection of ectocervical and endocervical cervical lesions. There was no statistically significant difference between both groups regarding parity, previous abortion, age at marriage, duration of marriage, and age at menarche and menopause. On unaided naked eye examination of the cervix (UNEE), there were no statistically significant differences between both groups. Diagnostic indices were similar in both groups apart from the finding that office cervicoscopy was more sensitive for detection of endocervical abnormalities. Doctors were significantly more satisfied with stationary colposcopy than office cervicoscopy. Office cervicoscopy is a good complementary tool added to stationary colposcopy for detection of cervical lesions in cases with suspicious cervix as an example of high-risk group for cervical cancer. Due to its small caliber, cervicoscopy offers a better evaluation of the endocervical canal, especially in cases of Type 2 and 3 transformation zone with a possibility of examination of the endometrial cavity.


PCR detection of DNA specific for Aspergillus species in serum of patients with invasive aspergillosis.
We investigated the possible presence of DNA specific for Aspergillus species in serum samples of patients with invasive aspergillosis (IA) by the nested PCR method. Fourteen strains of fungi including 5 strains of Aspergillus species and 10 strains of common bacteria were used for examination of specificity and sensitivity of the nested PCR. Two sets of oligonucleotide primers were derived from the sequence of the variable regions V7 to V9 of the 18S rRNA genes of Aspergillus fumigatus. The specific fragment was amplified from five strains of Aspergillus species in the single and nested PCR but not from other microorganisms. Target DNA was detected by the nested PCR with as little as 50 fg of the extracted DNA of A. fumigatus. We investigated the detection of DNA specific for Aspergillus species in serum samples of a murine model of aspergillosis and 20 patients with IA. The specific fragment was detected by the nested PCR in 71% of serum samples of infected mice and 70% of serum samples of patients with IA, while galactomannan antigen was detected in 43 and 60% of samples, respectively. The high sensitivity and specificity of the nested PCR indicate that the assay can provide early diagnosis with sufficient accuracy to be clinically useful for immunocompromised patients with IA.


Percutaneous self-expandable uncovered metallic stents in malignant biliary obstruction. Complications, follow-up and reintervention in 154 patients.
Evaluation of technique, complications and the long-term follow-up data of 154 patients with inoperable malignant biliary obstruction who underwent percutaneous placement of metallic stents. During a 6-year period, 224 self-expanding metallic stents (150 biliary Wallstents and 74 Memotherm nitinol stents) were inserted in 154 patients with inoperable malignant biliary obstruction. 100 patients had obstructions at the proximal (supracystic) level, and 54 at the distal (infracystic) level. The causes of obstructions were hilar cholangiocarcinoma (n = 64), pancreatic carcinoma (n = 34), gallbladder carcinoma (n = 24), metastatic carcinoma (n = 21), common bile duct carcinoma (n = 8), and hepatocellular carcinoma (n = 3). A complete follow-up was available for all patients. The 30-day mortality was 9%, with no procedure-related deaths. The clinical success rate within the first 30 days was 88%. The total rate of early, procedure-related complications was 28%, and half of them were due to the percutaneous transhepatic catheter drainage procedure. Recurrent jaundice occurred in 28 (18%) patients and in 23 (82%) of these, reinterventions were made in order to relieve reobstructions. The mean length of survival for the entire patient group was 4 months, while the mean period of patency for all stents was 6 months. We found no statistically significant difference in patient survival or stent patency periods in regard to the level and cause of obstruction. Percutaneous metallic stent placement maintains equal palliation in patients with proximal and distal malignant biliary obstructions caused by any tumor type. Most of the early complications were due to procedures performed before stent insertion and could be decreased by direct stent insertions. The most common late complication, reobstruction, is inevitable but can be easily treated in the majority of patients.


Auxin and cytokinin have opposite effects on amyloplast development and the expression of starch synthesis genes in cultured bright yellow-2 tobacco cells.
In cultured Bright Yellow-2 (BY-2) tobacco (Nicotiana tabacum) cells, the depletion of auxin (2,4-dichlorophenoxyacetic acid) in the culture medium induces the accumulation of starch. This is accelerated by the addition of cytokinin (benzyladenine). Light and electron microscopic observations revealed that this amyloplast formation involves drastic changes in plastid morphology. The effects of auxin and cytokinin on amyloplast development were investigated by adding auxin or cytokinin to cells grown in a hormone-free culture. Auxin repressed amyloplast development, whereas cytokinin accelerated starch accumulation regardless of the timing of hormone addition. RNA gel-blot analysis revealed that the accumulation of the ADP-glucose pyrophosphorylase small subunit gene (AgpS), granule-bound starch synthase, and starch branching enzyme transcripts were also affected by hormonal conditions. High levels of AgpS, granule-bound starch synthase, and starch branching enzyme transcripts accumulated in amyloplast-developing cells grown in auxin-depleted conditions. Furthermore, the addition of auxin to the cells cultured in hormone-free medium reduced the level of AgpS transcripts, whereas the addition of cytokinin increased it, irrespective of the timing of hormone addition. These results suggest that auxin and cytokinin exert opposite effects on amyloplast development by regulating the expression of the genes required for starch biosynthesis.


[Nursing process to patients with anorexia nervosa].
Experience report on the application of the nursing process (NP) to a female patient with Anorexia Nervosa patient, using patient history, diagnoses, nursing interventions and outcomes. The interventions were based on the nursing diagnoses: body image disturbance, altered nutrition less than body requirements, anxiety, chronic low self-esteem, activity intolerance, ineffective management of therapeutic regimen, risk for infection, fluid volume deficit and social isolation. Based on the application of the Nursing Process, the planned results were achieved, favoring a better quality of life during the patient's hospitalization time. Mental, neurological, endocrine and immunological factors, which are peculiar in anorexia nervosa cases, permitted the elaboration of an Nursing Process, which positively contributed to complement the patient's health rehabilitation.


Study on the effect and mechanism of chicken breast on the gel properties of silver carp (Hypophthalmichtys molitrix) surimi.
Adding appropriate exogenous substances is an effective means to improve the quality of freshwater fish surimi. The present study investigated the effects of chicken breast on the gel properties of mixed minced meat products. With the increase in the proportion of chicken breast, the breaking force of mixed gels gradually increased. When the addition ratio was 30:70, the gel strength of mixed gels had the highest strength of 759.00 g cm-1 and also the highest water holding capacity of 87.36%. Compared with surimi gels (0:100), the hardness, adhesiveness and chewiness of mixed gels were significantly improved. The increase in the proportion of chicken breast increased the thermal stability of the mixed sol and improved the rheological properties of the mixed sol. When the proportion was 40:60, the area of immobile water (A22 ) in the mixed gel increased significantly, and the highest A22 was 3463.24. The hydrophobic interactions and disulfide bonds in the mixed gel were significantly increased as a result of the addition of chicken breast. The results of microstructure, electrophoresis and Raman spectroscopy indicated that the addition of chicken breast promoted the cross-linking of the proteins in mixed gels, which facilitated the transformation of the protein secondary structure from α-helical to β-folded structure, thus forming a more uniform and orderly network structure. These results suggest that improving the gel properties of silver carp surimi by use of chicken breast has practical implications for the development of new blended products for surimi processing. © 2023 Society of Chemical Industry.


[A video based training in communication skills for physicians].
The aim of an "intensive training course in communication skills for physicians" is to train the perception of behaviour and of emotions in the doctor-patient communication. Core elements of the training are role plays on topics perceived as difficult and brought in by participants. From the group discussions arises a rich array of observations. The identical reproduction of a situation in time and space by means of video permits a variety of ways to check the perception of a situation and the communication skills. The approach is illustrated by an example taken from one exercise. 26 physicians participated in three courses. The repetition of the scene played at the first day is repeated with the same actors at the end of a training. Progress can be measured by comparing the two scenes. An evaluation by means of a structured questionnaire was carried out at the end of the training, after three and twelve months. The higher degree of self confidence on the part of the physicians could be seen from the analysis of the videos, from the comparison of the two videos and also from the questionnaires. Training by means of video takes time and energy. From the view of the authors and also from the participants this didactic approach to training is very effective. The training can be a building block towards a better care for patients.


Striatal kinetic modeling of FDOPA with a cerebellar-derived constraint on the distribution of volume of 30MFD: a PET investigation using non-human primates.
The peripherally born metabolite of FDOPA, 3-O-Methyl-FDOPA (3OMFD), crosses the blood-brain barrier, thus complicating positron emission tomography-FDOPA (PET-FDOPA) data analysis. In previous reports the distribution volume (DV) of 3OMFD was constrained to unity. We have recently shown that the forward transport rate-constant of FDOPA (K(S1)) and the cerebellum-to-plasma ratio (C(b)/C(p)), a measure for the DV of 3OMFD, are functions of plasma large neutral amino acid (LNAA) concentration. Given large interstudy and intersubject differences in plasma LNAA levels, variations in the DV of 3OMFD are significant. In this report, the authors propose a constraint on the DV of 3OMFD that accounts for these variations. Dynamic PET-FDOPA scans were performed on 12 squirrel monkeys and 12 vervet monkeys. Two sets of constraints were employed on the compartmental model--M1 or M2. In M1, the striatal DV of 3OMFD was constrained to unity; in M2, the striatal DV of 3OMFD was constrained to an estimate derived from the cerebellum. Striatal and cerebellar time-activity curves were fitted using FDOPA and 3OMFD plasma input functions. The estimate of K(S1) and that of the compartmental FDOPA uptake-constant (K(i)), both obtained using M2, were adjusted to values corresponding to average LNAA levels. Finally, K(i) was compared with the graphical uptake-constant (PK(j)). With the use of constraint M2, intersubject variability of squirrel monkey k(S3) and K(i) was reduced by 45% and 53%, respectively; and for vervet monkeys, by 54% and 44%, respectively. Intersubject variability of K(1) and K(i) was further reduced after correction for variations in intersubject plasma LNAA levels (for squirrel monkeys, by 67% and 41%; for vervet monkeys, by 40% and 36%, respectively). K(i) correlation to PK(i) was enhanced to identity. Finally, average cerebellar k(C2) estimates were more than 2.5-fold higher than striatal k(S2) estimates (P < 0.0001). In modeling of PET-FDOPA data, it cannot be assumed that the DV of 3OMFD is unity. The cerebellar-derived constraint furnishes a reliable estimate for the DV of 3OMFD. Invoking the constraint and correcting for variations in plasma LNAA significantly reduced interstudy and intersubject variations in parameter estimates.


Efficient isolation of wild strains of canine distemper virus in Vero cells expressing canine SLAM (CD150) and their adaptability to marmoset B95a cells.
We have previously shown that canine signaling lymphocyte activation molecule (SLAM; also known as CD150) acts as a cellular receptor for canine distemper virus (CDV). In this study, we established Vero cells stably expressing canine SLAM (Vero.DogSLAMtag cells). Viruses were isolated in Vero.DogSLAMtag cells one day after inoculation with spleen samples from five out of seven dogs with distemper. By contrast, virus isolation with reportedly sensitive marmoset B95a cells was only successful from three diseased animals at 7 to 10 days after inoculation, and no virus was recovered from any dogs when Vero cells were used for isolation. The CDV strain isolated in Vero.DogSLAMtag cells did not cause cytopathic effects in B95a and human SLAM-expressing Vero cells, whereas the strain isolated in B95a cells from the same dog did so in canine or human SLAM-expressing Vero cells as well as B95a cells. There were two amino acid differences in the hemagglutinin sequence between these strains. Cell fusion analysis after expression of envelope proteins and vesicular stomatitis virus pseudotype assay showed that their hemagglutinins were responsible for the difference in cell tropism between them. Site-directed mutagenesis indicated that glutamic acid to lysine substitution at position 530 of the hemagglutinin was required for the adaptation to the usage of marmoset SLAM. Our results indicate that Vero cells stably expressing canine SLAM are highly sensitive to CDV in clinical specimens and that only a single amino acid substitution in the hemagglutinin can allow the virus to adapt to marmoset SLAM.


Depression Rises the Risk of Hypertension Incidence: Discussing the Link through the Ca2+/cAMP Signalling.
Depression and hypertension are medical problems both with clearly restricted pharmacotherapies, along with a high prevalence around the world. In fact, an intensive discussion in the field is that a dysregulation of the intracellular Ca2+ homeostasis (e.g. excess of intracellular Ca2+) contributes to the pathogenesis of both hypertension and depression. Furthermore, depression rises the risk of hypertension incidence. Indeed, several data support the concept that depression is an independent risk issue for hypertension. Then, which are the possible cellular mechanisms involved in this link between depression and hypertension? Considering our previous reports about the Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling), in this review I have discussed the virtual involvement of the Ca2+/cAMP signalling in this link (between depression and hypertension). Then, it is important to consider depression into account during the process of prevention, and treatment, of hypertension.


[Therapeutic drug monitoring of clobazam].
Clobazam is a 1,5 benzodiazepine available in France since 1975, used in add-on with the other anticonvulsant drugs in the treatment of refractory epilepsies of child and adult and for the treatment of anxiety of adult. It is mainly metabolized in desmethylclobazam, or norclobazam, active metabolite, present in a concentration approximately eight times superior to that of the parent drug, but with an activity of the order of 20 to 40% of that of clobazam. Elimination half-life of clobazam is of 18 h while that of norclobazam is from 40 to 50 h. There is a large interindividual variability in the plasma concentrations. Furthermore, clobazam being prescribed in add-on with the other anticonvulsant drugs in resistant epilepsies, concentration-effect relationship is difficult to bring to light, since, in many studies, the patients who did not answer received the highest doses. Adverse reactions are moderated, appearing more often for the highest concentrations; also the phenomenon of tolerance seems more frequent in high concentrations. However, because of the kinetic interactions, a dosage of clobazam and norclobazam can be useful in certain cases. There is no validated therapeutic range, but the usual concentrations are in the range of 100-300 microg/L for the parent drug and about ten times more for the metabolite. The level of proof of the interest of the Therapeutic Drug Monitoring for this molecule is estimated in: rather useless.


[The influence of ITGB3 gene polymorphism on the frequency of arterial hypertension in patients with acute coronary syndrome].
PLA polymorphism of platelet integrin receptor, GpIIIa glycoprotein, (PLA polymorphism of the ITGB3 gene) is associated with the risk of myocardial infarction and CHD especially in young subjects. We analyzed ITGB3 gene polymorphism in patients with acute coronary insufficiency. It was shown that increased AP and altered blood lipid spectrum in the acute period of disease in carriers of the PLA allele (PLA1/PLA2 and PLA2/PLA2 genotypes) can be regarded as manifestations of stress reaction. The data obtained indicate that the PLA2 allele is a predictor of complications of acute coronary insufficiency. This observation is of importance for the choice of adequate therapy for the patients with this disorder.


Bad little girls.
The characters, in little girl style, who more and more often appear in advertisements, glossy magazines, television programs and megastores, and who can be encountered in the streets of many cities, are not the product of an ephimerous fashion dictated by the logic of the market. They come from far away, disquieting and erotic, and have crossed all the cultures of the western world, fascinating and disconcerting the soul with their power of seduction. They are the nymphs of Greek mythology, and not even the gods were able to resist them, knowing very well that their bodies are a place of knowledge that could lead to insanity. The paradox of the nymph is that possessing her means being possessed. After an overview of the myth of possession by nymphs, the author discusses certain illustrious figures of western culture of the 19th and 20th century possessed by a nymph: Aby Warburg, Martin Heidegger, Carl Gustav Jung, Henrik Ibsen and Emil Cioran. In all of them the possession by a nymph unfolded in keeping with the myth: intellectual fervor was common to all, insanity in Warburg, rapacious egotism in Heidegger and Jung, and a metamorphosis of Weltanshaung in Ibsen and Cioran. Nonetheless, they all, in their encounter with a nymph, laid bare their multifaceted identities, the muddy depths and the "heart of darkness" of their souls.


An external delta-carbonic anhydrase in a free-living marine dinoflagellate may circumvent diffusion-limited carbon acquisition.
The oceans globally constitute an important sink for carbon dioxide (CO(2)) due to phytoplankton photosynthesis. However, the marine environment imposes serious restraints to carbon fixation. First, the equilibrium between CO(2) and bicarbonate (HCO(3)(-)) is pH dependent, and, in normal, slightly alkaline seawater, [CO(2)] is typically low (approximately 10 mum). Second, the rate of CO(2) diffusion in seawater is slow, so, for any cells unable to take up bicarbonate efficiently, photosynthesis could become carbon limited due to depletion of CO(2) from their immediate vicinity. This may be especially problematic for those dinoflagellates using a form II Rubisco because this form is less oxygen tolerant than the usually found form I enzyme. We have identified a carbonic anhydrase (CA) from the free-living marine dinoflagellate Lingulodinium polyedrum that appears to play a role in carbon acquisition. This CA shares 60% sequence identity with delta-class CAs, isoforms so far found only in marine algae. Immunoelectron microscopy indicates that this enzyme is associated exclusively with the plasma membrane. Furthermore, this enzyme appears to be exposed to the external medium as determined by whole-cell CA assays and vectorial labeling of cell surface proteins with (125)I. The fixation of (14)CO(2) is strongly pH dependent, suggesting preferential uptake of CO(2) rather than HCO(3)(-), and photosynthetic rates decrease in the presence of 1 mm acetazolamide, a non-membrane-permeable CA inhibitor. This constitutes the first CA identified in the dinoflagellates, and, taken together, our results suggest that this enzyme may help to increase CO(2) availability at the cell surface.


Heterogeneity of human peripheral blood monocyte subsets.
In recent years the number of reports describing phenotypically and functionally distinct subsets of human blood leukocytes, and in particular of subtypes of antigen-presenting cells has continuously increased. A great diversity was described not only for dendritic cells (DC), but also for human blood monocytes (Mo) and macrophages (Mac). Similar to DC, the different types of Mo subsets could be defined by distinct phenotypes and immunoregulatory functions. The characterization of blood Mo subpopulations revealed that some of them exhibit common features with myeloid or lymphoid DC and tissue Mac, but also demonstrate the existence of novel unique cell populations. The generation of lymphoid and myeloid DC and their heterogeneity has been the subject of recent reviews. Here we focus on Mo from human peripheral blood and summarize the data (including our own) dealing with their phenotypic and functional, in particular immunoregulatory properties.


G protein coupling of receptors to ionic channels and other effector systems.
1. Four questions raised by previous studies that had shown activation of K+ channels by alpha subunits of the type 3 Gi protein are addressed in the present communication: a) are K+ channels specific for one Gi? b) are there more ionic channels under direct G protein control? c) can we confirm using recombinant G alpha s the results obtained with biochemically resolved G alpha s and continue ascribing the regulatory effector to this part of the alpha beta gamma holo-G protein? and d) can we confirm that a single G alpha, Gs alpha in this case, is able to affect more than one type of effector function? 2. We found Gi alpha s are isoforms, that there exist also Gi-insensitive, Go-responsive K+ channels and that G alpha s can be multifunctional. Thus, a single receptor will elicit cellular responses that will depend on the endogenous G protein as well as the type of effector function expressed in it. 3. In another set of experiments we found that G beta gamma s, be they derived from human erythrocytes, human placenta, bovine brain or bovine retina, all inhibit Gk-gated K+ channel activity as seen in inside out membrane patches with GTP as the driving nucleotide. In addition we noted that inhibition was much more effective under basal (no agonist in the pipette) than agonist stimulated conditions, as reported in earlier experiments in which beta-adrenoceptors, Gs and catalytic unit of adenylyl cyclase had been incorporated into phospholipid vesicles. 4. We propose that one of the roles of G beta gamma s in membranes is to quench ligand independent G protein activation by unoccupied receptors. Other roles of G beta gamma s are: a) by re-associating with GDP-G alpha s, to promote interaction with receptors, and b) by dissociating from activated R.G alpha *GTP.beta gamma, to allow for receptor dissociation from GTP-activated G alpha s, which is required to satisfy the catalytic mode of receptor action.


Implementation of a retrofit MRI simulator for radiation therapy planning.
Magnetic resonance imaging (MRI) is being integrated into routine radiation therapy (RT) planning workflows. To reap the benefits of this imaging modality, patient positioning, image acquisition parameters and a quality assurance programme must be considered for accurate use. This paper will report on the implementation of a retrofit MRI Simulator for RT planning, demonstrating an economical, resource efficient solution to improve the accuracy of MRI in this setting.


Paraprofessionals and caring practice: negotiating the use of self.
Responding to increasing concerns with the quality of care in both Sweden and England, this paper explores the way in which caring practice emerges out of the interplay between personal and social agency. Working from a socio-cultural perspective, results from an English and a Swedish study conducted independently of each other were used to explore the construction of caring practice. The English study drew on practice observations and four interviews conducted at monthly intervals collecting data on life history and critical incidents. The Swedish study drew on group interviews and two interviews with each participant - one at the beginning of an in-service recognition of prior learning process and one at the end. Interview data was transcribed and thematic analysis identified common themes. The findings from both studies suggest that caring practice involves the intentional use of self to build relationships, understand users and provide personalised interventions. Although practice presented as personal and individualistic, it took place within an organisational context requiring co-configured activity. The practitioners' negotiations with work teams were often conflictual or contested. It is argued that workplaces may enhance caring practice by enabling affordances for the use of self through the design of in-house training programmes, supervision and the organisation of teams. Reflexive practice may also be an important part of the effective use of self.


Emodiversity, health, and well-being in the Midlife in the United States (MIDUS) daily diary study.
Emodiversity, or the variety and relative abundance of emotions experienced, provides a metric that can be used to understand emotional experience and its relation to well-being above and beyond average levels of positive and negative affect. Past research has found that more diverse emotional experiences, both positive and negative, are related to better mental and physical health outcomes. The present research aimed to test the relationship between positive and negative emodiversity across the span of 8 days with measures of health and well-being using 2 samples of the Midlife in the United States study (http://midus.wisc.edu/). Participants (N = 2,788) reported emotional states (14 negative, 13 positive) once each day for 8 days. Emodiversity scores were computed for each day using an adaptation of Shannon's biodiversity index and averaged across the days. All models included average affect and demographic covariates. Greater positive emodiversity was associated with fewer symptoms of depression and anxiety and fewer physical health symptoms but was not related to eudaimonic well-being nor cognitive functioning. In contrast to previous research, greater negative emodiversity was related to more symptoms of depression and anxiety and more physical health symptoms. Greater negative emodiversity was only associated with one positive outcome: better executive functioning. These findings illustrate inconsistencies across studies in whether negative emodiversity is associated with better or worse outcomes and raise further questions about how the construct of emodiversity can be better refined. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Myelin-Associated Glycoprotein Inhibits Schwann Cell Migration and Induces Their Death.
Remyelination of CNS axons by Schwann cells (SCs) is not efficient, in part due to the poor migration of SCs into the adult CNS. Although it is known that migrating SCs avoid white matter tracts, the molecular mechanisms underlying this exclusion have never been elucidated. We now demonstrate that myelin-associated glycoprotein (MAG), a well known inhibitor of neurite outgrowth, inhibits rat SC migration and induces their death via γ-secretase-dependent regulated intramembrane proteolysis of the p75 neurotrophin receptor (also known as p75 cleavage). Blocking p75 cleavage using inhibitor X (Inh X), a compound that inhibits γ-secretase activity before exposing to MAG or CNS myelin improves SC migration and survival in vitro Furthermore, mouse SCs pretreated with Inh X migrate extensively in the demyelinated mouse spinal cord and remyelinate axons. These results suggest a novel role for MAG/myelin in poor SC-myelin interaction and identify p75 cleavage as a mechanism that can be therapeutically targeted to enhance SC-mediated axon remyelination in the adult CNS.SIGNIFICANCE STATEMENT Numerous studies have used Schwann cells, the myelin-making cells of the peripheral nervous system to remyelinate adult CNS axons. Indeed, these transplanted cells successfully remyelinate axons, but unfortunately they do not migrate far and so remyelinate only a few axons in the vicinity of the transplant site. It is believed that if Schwann cells could be induced to migrate further and survive better, they may represent a valid therapy for remyelination. We show that myelin-associated glycoprotein or CNS myelin, in general, inhibit rodent Schwann cell migration and induce their death via cleavage of the neurotrophin receptor p75. Blockade of p75 cleavage using a specific inhibitor significantly improves migration and survival of the transplanted Schwann cells in vivo.


CD40-1C>T polymorphism (rs1883832) is associated with brain vessel reocclusion after fibrinolysis in ischemic stroke.
To find genetic predictors of reocclusion after successful fibrinolytic therapy during the acute phase of ischemic stroke. This was a case-case prospective study analyzing 236 polymorphisms in a cohort of 222 patients treated with tissue plasminogen activator, from which 16 patients suffered a reocclusion event (7.2%). A predictive scale was generated using independent polymorphisms with a dominant/recessive model and tandem occlusion, weighted by their beta-coefficients in logistic regression. Using a dominant/recessive model, the rs1800801 SNP from the MGP gene (odds ratio [OR]: 15.25; 95% CI: 2.23-104.46; adjusted p = 0.006) and the rs1883832 SNP from CD40 gene (OR: 0.077; 95% CI: 0.009-0.66; adjusted p = 0.019) were independently associated with reocclusion after logistic regression adjustment by clinical predictors. In an additive model, only the rs1883832 SNP (OR: 4.43; 95% CI: 1.62-12.15; adjusted p = 0.004) was related to reocclusion occurrence. The predictive model that was generated stratified the reocclusion risk from less than 1% to more than 70%. Reocclusions were associated with neurological worsening at 24 h (patients with reocclusion: 26.7%, versus patients without reocclusion: 4.9%; p = 0.002), as it was seen for MGP -7A>G (AA: 17.2% vs AG+GG: 4.5%; p = 0.027), but not for CD40 1C>T (CC: 4.5% vs CT+TT: 7.7%; p = 0.565). There was an association between CD40 -1C>T genotype and CD40 transcriptional activity in peripheral blood mononuclear cells (median expression values TT: 65.75%, CT: 70.80%, CC: 96.00%; p = 0.023). However, CD40 soluble fraction was not a useful biomarker of reocclusion status. An association was found between MGP -7A>G and CD40 -1C>T polymorphisms, and reocclusion risk. The predictive scale that was generated permits the stratification of patients by their reocclusion risk with higher accuracy than clinical parameters alone.


Perspectives on Stress, Parenting, and Children's Obesity-Related Behaviors in Black Families.
Objective In an effort to develop targets for childhood obesity interventions in non-Hispanic-Black (Black) families, this study examined parental perceptions of stress and identified potential links among parental stress and children's eating patterns, physical activity, and screen-time. Method Thirty-three self-identified Black parents or grandparents of a child aged 3 to 7 years were recruited from a large, urban Black church to participate in semistructured interviews. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis. Results Parents/grandparents described a pathway between how stress affected them personally and their child's eating, structured (sports/dance) and unstructured (free-play) physical activity, and screen-time usage, as well as strategies to prevent this association. Five themes emerged: stress affects parent behaviors related to food and physical activity variably; try to be healthy even with stress; parent/grandparent stress eating and parenting; stress influences family cooking, food choices, and child free-play; and screen-time use to decrease parent stress. Negative parent/grandparent response to their personal stress adversely influenced food purchases and parenting related to child eating, free-play, and screen-time. Children of parents/grandparents who ate high-fat/high-sugar foods when stressed requested these foods. In addition to structured physical activity, cooking ahead and keeping food in the house were perceived to guard against the effects of stress except during parent cravings. Parent/child screen-time helped decrease parent stress. Conclusion Parents/grandparents responded variably to stress which affected the child eating environment, free-play, and screen-time. Family-based interventions to decrease obesity in Black children should consider how stress influences parents. Targeting parent cravings and coping strategies that utilize structure in eating and physical activity may be useful intervention strategies.


Comparison of the effects of disodium ethylenediaminetetraacetate, theophylline, and deoxycholic acid on colonic ion transport and permeability.
The effects of ethylenediaminetetraacetate (EDTA), theophylline, and deoxycholic acid (DCA) on colonic ion transport and permeability were examined in an isolated loop system of the pig colon. The 3 agents abolished net water absorption, but only EDTA and DCA induced an increase in mucosal permeability. Theophylline resulted in active bicarbonate secretion and increased the transmural electrical potential difference, whereas DCA resulted in a dose-dependent inhibition of the theophylline-stimulated potential difference and antagonized or abolished the effect of theophylline on ion transport. A similar inhibition of the sodium transport potential across the mucosa resulted with DCA. The effects of DCA on the potential difference were immediate and reversible and paralleled the changes in colonic permeability. These results are consistent with the hypothesis that the mechanism of bile acid-induced diarrhea is through an increase in mucosal permeability and/or mucosal damage. Evidence of an active secretory process was not demonstrable with this preparation.


[Features of diagnosis and clinics of gallbladder cholesterosis in children].
Cholesterosis in childhood--this is a new poorly studied disease, which only begins to highlight in current literature. According to this our work was to study the clinical characteristics and to develop diagnostic criteria of gall bladder cholesterosis in children. 66 children with cholesterosis gall bladder at the age of 1 year to 15 years were under the supervision. There were 30 girls and 36 boys. The diagnosis was confirmed in the performance of transabdominal ultrasound examination and endoscopic (transesophageal) ultrasonography, magnetic resonance tomography. The cholesterosis of the gall bladder was confirmed by histological examination of the gall bladder wall at 41 children. This article describes the clinical course of gall bladder cholesterosis in children. It was shown an importance of laboratory and instrumental methods of investigation. It was presented an algorithm of children diagnostics and monitoring with gallbladder cholesterosis.


The role of a water bug, Sigara striata, in freshwater food webs.
Freshwater food webs are dominated by aquatic invertebrates whose trophic relationships are often poorly known. Here, I used laboratory experiments to study the role of a water bug, Sigara striata, as a potential predator and prey in food webs of stagnant waters. Multiple-choice predation experiment revealed that Sigara, which had been considered mostly herbivorous, also consumed larvae of Chironomus midges. Because they often occur in high densities and are among the most ubiquitous aquatic insects, Sigara water bugs may be important predators in fresh waters. A second experiment tested the role of Sigara as a potential prey for 13 common invertebrate predators. Mortality of Sigara inflicted by different predators varied widely, especially depending on body mass, foraging mode (ambush/searching) and feeding mode (chewing/suctorial) of the predators. Sigara was highly vulnerable to ambush predators, while searching predators caused on average 8.1 times lower mortality of Sigara. Additionally, suctorial predators consumed on average 6.6 times more Sigara individuals than chewing predators, which supports previous results hinting on potentially different predation pressures of these two types of predators on prey populations. The importance of these two foraging-related traits demonstrates the need to move from body mass based to multiple trait based descriptions of food web structure. Overall, the results suggests that detailed experimental studies of common but insufficiently known species can significantly enhance our understanding of food web structure.


Surface plasmon mediated energy transfer of electrically-pumped excitons.
We report strong surface plasmon polariton mediated transfer of energy between molecular excitons across the metallic cathode of an electrically-pumped organic heterostructure. The donor molecular excitons at the organic heterojunction resonantly excite surface plasmon modes on both sides of the optically thick metal electrode, which evanescently couple to dye molecules near the electrode's exterior surface. Dye fluorescence in the capping layer on the exterior of the device shows a 6.5-fold increase in intensity due to this effect, far exceeding any enhancement attributable to Purcell or optical microcavity effects. Demonstration of this energy transfer mechanism for electrically-pumped excitons suggests new sensing and imaging applications with high signal to noise ratio and new routes for performance improvement in energy harvesting devices, plasmonic devices, and organic LEDs (including white light emission).


tRNA-Cys gene clusters exhibit high variability in Arabidopsis thaliana.
Although most of the genes encoding tRNAs in plants are dispersed throughout the genome, a fraction of them form tRNA gene clusters. In Arabidopsis thaliana, the smallest of tRNA clusters on chromosome 5 consists of four tRNA-Cys-GCA genes placed within repeating units of 0.4 kbp. A systematic analysis of the genomic sequences of syntenic regions from various ecotypes of A. thaliana showed that the general structure of the cluster, consisting of a tRNA-Cys pseudogene followed by repeating units containing tRNA-Cys genes, is well conserved. However, there is significant heterogeneity in the number of repeating units between different ecotypes. A unique feature of this cluster is the presence of putative transposable elements (Helitron). In addition, two further tRNA-Cys gene mini-clusters (gene pairs) in A. thaliana were identified. RNA-seq-based evaluation of expression of tRNA-Cys-GCA genes showed a positive signal for 11 out of 13 unique transcripts. An analysis of the conservation of the tRNA-Cys clusters from A. thaliana with the corresponding regions from four other Arabidopsis species suggests a sequence of events that led to the divergence of these regions.


[Efficacy of transurethral resection of ejaculatory duct for treatment of ejaculatory duct obstruction: report of 60 cases].
To evaluate the effect of transurethral resection of ejaculatory duct (TURED) for treatment of ejaculatory duct obstruction (EDO). The clinical data of 60 cases of EDO from Oct. 2004 to Oct. 2010 were analyzed. The diagnostic criteria included semen analyses, fructose in seminal plasma, transrectal ultrasonography (TRUS), and vasography if necessary. All the patients were treated by TURED. Post-operative semen assay, postoperative patency rate and postoperative impregnation rate were followed. Semen analyses in the majority of cases showed the typical characteristics of EDO, azoospermia, low semen volume (average 1.10 ± 0.76 mL), low pH (average 6.5 ± 1.4), absent or low semen fructose (average 5.86 ± 2.19 μmol/one ejaculation). TRUS showed pure dilation of both ejaculatory ducts in 15 cases, prostatic cyst in 6, pure dilated seminal vesicles on both sides in 10, unilateral dilated seminal vesicle in 4, dilation of both ejaculatory duct and seminal vesicles in 10, dilated seminal vesicles with prostatic cyst in 5, unilateral dilated seminal vesicle and contralateral aplasia of seminal vesicle in 2, dilated seminal vesicles with dilation and calcifications of both ejaculatory ducts in 3. The remaining 5 had unilateral dilated ejaculatory duct and seminal vesicle with contralateral aplasia of seminal vesicle. In all the cases followed up more than 6 to 78 months after TURED, 51 patients (85.0%) had improved semen parameters and 16 patients' wives (26.7%) had pregnancies. TURED may be the simple, minimally invasive and effective method for the treatment of EDO.


The correlation between central and peripheral oxytocin concentrations: A systematic review and meta-analysis.
There is growing interest in the role of the oxytocin system in social cognition and behavior. Peripheral oxytocin concentrations are regularly used to approximate central concentrations in psychiatric research, however, the validity of this approach is unclear. Here we conducted a pre-registered systematic search and meta-analysis of correlations between central and peripheral oxytocin concentrations. A search of databases yielded 17 eligible studies, resulting in a total sample size of 516 participants and subjects. Overall, a positive association between central and peripheral oxytocin concentrations was revealed [r=0.29, 95% CI (0.14, 0.42), p<0.0001]. This association was moderated by experimental context [Qb(4), p=0.003]. While no association was observed under basal conditions (r=0.08, p=0.31), significant associations were observed after intranasal oxytocin administration (r=0.66, p<0.0001), and after experimentally induced stress (r=0.49, p=0.001). These results indicate a coordination of central and peripheral oxytocin release after stress and after intranasal administration. Although popular, the approach of using peripheral oxytocin levels to approximate central levels under basal conditions is not supported by the present results.


Polyphenolic profile and biological activities of black carrot crude extract (Daucus carota L. ssp. sativus var. atrorubens Alef.).
Black carrot (Daucus carota L. ssp. sativus var. atrorubens Alef.) is a valuable source of carbohydrates, minerals and vitamins and contains also high amounts of anthocyanins giving the characteristic deep-purple color. These latter compounds are known as natural dyes used in the food and pharmaceutical industry that have recently attracted much attention for their healthful properties. The aim of this work was to investigate for the first time the polyphenolic profile and biological properties of a black carrot crude extract (BCCE) through an in-depth analysis of the main polyphenolic classes evaluating its antioxidant, cytoprotective and anti-angiogenic properties. Twenty five polyphenols were quantified by LC-DAD-FLD-MS/MS analysis (anthocyanins 78.06%, phenolic acids 17.89% and other flavonoids 4.06%) with polyglycosylated cyanidins as major components. In addition, BCCE showed a strong antioxidant and free radical scavenging activity particularly in the hydrogen transfer-based assays (ORAC and β-carotene bleaching) and a significant increase in the cell viability. Furthermore, BCCE exhibited a strong anti-angiogenic activity at the highest concentration assayed on the chick chorioallantoic membrane (50μg/egg). In conclusion, the obtained results demonstrated the antioxidant, cytoprotective and anti-angiogenic properties of BCCE, which highlight that the higher biological activity of BCCE is probably due to the synergic effects exerted by various polyphenolic classes.


A late origin of the extant eukaryotic diversity: divergence time estimates using rare genomic changes.
Accurate estimation of the divergence time of the extant eukaryotes is a fundamentally important but extremely difficult problem owing primarily to gross violations of the molecular clock at long evolutionary distances and the lack of appropriate calibration points close to the date of interest. These difficulties are intrinsic to the dating of ancient divergence events and are reflected in the large discrepancies between estimates obtained with different approaches. Estimates of the age of Last Eukaryotic Common Ancestor (LECA) vary approximately twofold, from ~1,100 million years ago (Mya) to ~2,300 Mya. We applied the genome-wide analysis of rare genomic changes associated with conserved amino acids (RGC_CAs) and used several independent techniques to obtain date estimates for the divergence of the major lineages of eukaryotes with calibration intervals for insects, land plants and vertebrates. The results suggest an early divergence of monocot and dicot plants, approximately 340 Mya, raising the possibility of plant-insect coevolution. The divergence of bilaterian animal phyla is estimated at ~400-700 Mya, a range of dates that is consistent with cladogenesis immediately preceding the Cambrian explosion. The origin of opisthokonts (the supergroup of eukaryotes that includes metazoa and fungi) is estimated at ~700-1,000 Mya, and the age of LECA at ~1,000-1,300 Mya. We separately analyzed the red algal calibration interval which is based on single fossil. This analysis produced time estimates that were systematically older compared to the other estimates. Nevertheless, the majority of the estimates for the age of the LECA using the red algal data fell within the 1,200-1,400 Mya interval. The inference of a "young LECA" is compatible with the latest of previously estimated dates and has substantial biological implications. If these estimates are valid, the approximately 1 to 1.4 billion years of evolution of eukaryotes that is open to comparative-genomic study probably was preceded by hundreds of millions years of evolution that might have included extinct diversity inaccessible to comparative approaches. This article was reviewed by William Martin, Herve Philippe (nominated by I. King Jordan), and Romain Derelle.


The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial morphology and virulence.
Aspergillus fumigatus, an important opportunistic pathogen which commonly affects neutropenic patients, produces conidia with a bluish-green color. We identified a gene, alb1, which is required for conidial pigmentation. The alb1 gene encodes a putative polyketide synthase, and disruption of alb1 resulted in an albino conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb transcript is detected only during the conidiation stage. The alb1 mutation was found to block 1,3,6,8-tetrahydroxynaphthalene production, indicating that alb1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron microscopy studies showed that the alb1 disruptant exhibited a smooth conidial surface, whereas complementation of the alb1 deletion restored the echinulate wild-type surface. Disruption of alb1 resulted in a significant increase in C3 binding on conidial surfaces, and the conidia of the alb1 disruptant were ingested by human neutrophils at a higher rate than were those of the wild type. The alb1-complemented strain producing bluish-green conidia exhibited inefficient C3 binding and neutrophil-mediated phagocytosis quantitatively similar to those of the wild type. Importantly, the alb1 disruptant had a statistically significant loss of virulence compared to the wild-type and alb1-complemented strains in a murine model. These results suggest that disruption of alb1 causes pleiotropic effects on conidial morphology and fungal virulence.


Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: A model-based analysis.
The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID) a public health priority. Some of these programs have benefits beyond prevention of HIV-a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT), needle and syringe programs (NSPs), HIV testing and treatment (Test & Treat), and oral HIV pre-exposure prophylaxis (PrEP). We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars), health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs) of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively) and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22,000 (95% CI: 5,200, 46,000) infections and cost US$18,000 (95% CI: US$14,000, US$24,000) per QALY gained, 50% NSP coverage could avert up to 35,000 (95% CI: 8,900, 43,000) infections and cost US$25,000 (95% CI: US$7,000, US$76,000) per QALY gained, 50% Test & Treat coverage could avert up to 6,700 (95% CI: 1,200, 16,000) infections and cost US$27,000 (95% CI: US$15,000, US$48,000) per QALY gained, and 50% PrEP coverage could avert up to 37,000 (22,000, 58,000) infections and cost US$300,000 (95% CI: US$162,000, US$667,000) per QALY gained. When coverage expansions are allowed to include combined investment with other programs and are compared to the next best intervention, the model projects that scaling OAT coverage up to 50%, then scaling NSP coverage to 50%, then scaling Test & Treat coverage to 50% can be cost-effective, with each coverage expansion having the potential to cost less than US$50,000 per QALY gained relative to the next best portfolio. In probabilistic sensitivity analyses, 59% of portfolios prioritized the addition of OAT and 41% prioritized the addition of NSPs, while PrEP was not likely to be a priority nor a cost-effective addition. Our findings are intended to be illustrative, as data on achievable coverage are limited and, in practice, the expansion scenarios considered may exceed feasible levels. We assumed independence of interventions and constant returns to scale. Extensive sensitivity analyses allowed us to assess parameter sensitivity, but the use of a dynamic compartmental model limited the exploration of structural sensitivities. We estimate that OAT, NSPs, and Test & Treat, implemented singly or in combination, have the potential to effectively and cost-effectively prevent HIV in US PWID. PrEP is not likely to be cost-effective in this population, based on the scenarios we evaluated. While local budgets or policy may constrain feasible coverage levels for the various interventions, our findings suggest that investments in combined prevention programs can substantially reduce HIV transmission and improve health outcomes among PWID.


Characterizing glucose exposure for individuals with normal glucose tolerance using continuous glucose monitoring and ambulatory glucose profile analysis.
Efforts to mimic euglycemia depend upon targets from epidemiologic studies that rely on episodic measurements reduced to statistical summaries, leaving open the question, "What is normal glycemia?" We postulated that portrayal of euglycemia was possible through application of continuous glucose monitoring (CGM) and a novel analytical tool, the ambulatory glucose profile (AGP). Individuals with normal glucose tolerance (NGT) and with diabetes used CGM for 30 days. AGP analysis, which graphs CGM data by time without regard to date, was used to characterize glucose exposure, variability, and stability. Sixty-two subjects completed the study, employing CGM for 28 +/- 4 days averaging 99 +/- 18 (range, 33-125) readings per day. NGT subjects (n = 32) had a mean CGM of 102 +/- 7 mg/dL, ranging between 94 and 117 mg/dL and averaging 105 +/- 8 mg/dL daytime and 97 +/- 6 mg/dL overnight. Glucose variability, as expressed by the interquartile range, was 21 +/- 4 mg/dL (range, 14-29 mg/dL). Stability in glycemic control (hourly change in the median) for NGT subjects averaged 3 +/- 1 mg/dL/h. Subjects with diabetes (n = 30) were significantly higher on all glycemic characteristics with the exception of the percentage of hypoglycemic (CGM <70 mg/dL) episodes for type 2 diabetes (2.9%), compared to 2.7% for subjects with NGT. CGM technologies enabled collection of verified data under normal living conditions, providing an exceptional vantage point from which to obtain important clinical information. This will facilitate an understanding of the range of euglycemic patterns, provide a sensitive means of detecting impaired glucose tolerance, and help set realistic treatment goals for individuals with diabetes.


Capsaicin as an in vitro inhibitor of benzo(a)pyrene metabolism and its DNA binding in human and murine keratinocytes.
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the active principle of capsicum fruits, such as hot peppers, is a known inhibitor of substance P. This substance was also found to be a potent in vitro inhibitor of human and murine epidermal metabolism of benzo(a)pyrene (BP) and the enzyme-mediated binding of BP metabolites to DNA. In both untreated and 3-methylcholanthrene-treated neonatal rat epidermal microsomes, capsaicin resulted in a dose-dependent inhibition of aryl hydrocarbon hydroxylase activity with an I50 value of 3.0 X 10(-4)-3.6 X 10(-4) M. A Lineweaver-Burk plot of the inhibition of aryl hydrocarbon hydroxylase activity suggested that the inhibition is of the noncompetitive type with Ki value of 50 microM. Capsaicin also inhibited BP metabolism and the binding of 3H-BP to DNA in BALB/c mouse and human keratinocytes. The formation of BP-7,8-diol was also substantially diminished in both systems in the presence of capsaicin (180-300 microM). Our results indicate that the substance P inhibitor, capsaicin, is also an inhibitor of epidermal BP metabolism and DNA binding of its metabolites. Therefore, in addition to its neurological effects, capsaicin may represent a new category of compound with anti-carcinogenic effects.


Ensuring uninterrupted supplies of antiretroviral drugs in resource-poor settings: an example from Malawi.
Drug procurement and distribution practices are weak in many resource-poor countries, and are a major reason for lack of access to medicines. With many countries scaling up antiretroviral therapy (ART), it is vital to avoid interrupted drug supplies, which would lead to drug resistance and treatment failure. Malawi has adapted a model, based on that adopted by the country's Tuberculosis Control Programme, to allow rational ART drug forecasting. The model includes a focus on one standardized first-line ART regimen; a "push system" and "ceilings" for first-line ART drugs for facilities; use of starter pack and continuation pack kits; quarterly monitoring of patient outcomes and ART drug stocks at facility level; provision of a three-month buffer stock of ART drugs at facility level; and use of a procurement and distribution system outside central medical stores. The focus on a single first-line regimen, "ceilings" for first-line ART drugs and quarterly data collections to calculate drug needs (for new and follow-up patients, respectively), as well as the use of an independent procurement facility, allow drug orders to be made 6-9 months ahead. These measures have so far ensured that there have been no ART drug stock-outs in the country.


Expression of human BRCA2 in Saccharomyces cerevisiae complements the loss of RAD52 in double-strand break repair.
BRCA2 is a tumor-suppressor gene that is normally expressed in the breast and ovarian tissue of mammals. The BRCA2 protein mediates the repair of double-strand breaks (DSBs) using homologous recombination, which is a conserved pathway in eukaryotes. Women who express missense mutations in the BRCA2 gene are predisposed to an elevated lifetime risk for both breast cancer and ovarian cancer. In the present study, the efficiency of human BRCA2 (hBRCA2) in DSB repair was investigated in the budding yeast Saccharomyces cerevisiae. While budding yeast does not possess a true BRCA2 homolog, they have a potential functional homolog known as Rad52, which is an essential repair protein involved in mediating homologous recombination using the same mechanism as BRCA2 in humans. Therefore, to examine the functional overlap between Rad52 in yeast and hBRCA2, we expressed the wild-type hBRCA2 gene in budding yeast with or without Rad52 and monitored ionizing radiation resistance and DSB repair efficiency. We found that the expression of hBRCA2 in rad52 mutants increases both radiation resistance and DSB repair frequency compared to cells not expressing BRCA2. Specifically, BRCA2 improved the protection against ionizing radiation by at least 1.93-fold and the repair frequency by 6.1-fold. In addition, our results show that homology length influences repair efficiency in rad52 mutant cells, which impacts BRCA2 mediated repair of DSBs. This study provides evidence that S. cerevisiae could be used to monitor BRCA2 function, which can help in understanding the genetic consequences of BRCA2 variants and how they may contribute to cancer progression.


Younger and older adults' memory of past feelings surrounding an election.
People often misremember their past feelings, especially when recalling their prior mood as opposed to their specific emotions in response to events. A previous study also found that the direction of memory errors varies based on feeling type; younger adults overestimated the intensity of prior moods but underestimated the intensity of prior event-specific emotions. This study aimed to replicate these patterns and test whether they vary with age. In doing so, we also tested whether an age-related positivity effect would emerge, such that older adults would be relatively more likely to overestimate past positive feelings and underestimate past negative feelings. Using a sample of American voters, who reported their feelings following the 2020 United States presidential election, we found that both younger and older adults subsequently overestimated the intensity of their past mood in the week following the election but were relatively accurate in recalling the intensity of their prior emotions about the election result. Unexpectedly, among election losers, we also observed an age-related negativity effect in recall for prior mood. When faced with negative real-world events, older adults may not show the same positivity biases that are observed in lab studies.


Rat hepatic prolactin receptor: pubertal exposure to sex steroids alters responsivity to testosterone.
Administration of testosterone enanthate to adult female rats lowered the level of hepatic prolactin receptor. Pubertal exposure of intact female rats to testosterone enanthate at the dose used did not affect the level of hepatic prolactin receptor in adults. However, the responsivity of such treated rats to testosterone challenge in adulthood was enhanced. Prepubertal ovariectomy of female rats lowered the level of hepatic prolactin receptor in adulthood. Exposure of the ovariectomized rats during puberty to mestranol (ethynylestradiol 3-methyl ether) at the dose used did not restore the normal adult female rat's level of hepatic prolactin receptor. However, they did become more resistant to subsequent testosterone challenge in adulthood. Exposure of prepubescent ovariectomized rats to testosterone enanthate during puberty reduced the already diminished level of hepatic prolactin receptor further. In addition, these rats were rendered more responsive to testosterone challenge in adulthood.


Extra-plaque rotational atherectomy for treating a balloon uncrossable ostial right coronary artery chronic total occlusion.
Performing atherectomy in the subintimal space remains controversial. We describe a case of successful ostial right coronary artery CTO recanalization using rotational atherectomy in subintimal space.


Efficacy of Wholistic Turmeric Supplement on Adenomatous Polyps in Patients with Familial Adenomatous Polyposis-A Randomized, Double-Blinded, Placebo-Controlled Study.
Several studies have demonstrated that curcumin can cause the regression of polyps in familial adenomatous polyposis (FAP), while others have shown negative results. Wholistic turmeric (WT) containing curcumin and additional bioactive compounds may contribute to this effect. We performed a double-blinded, randomized, controlled trial to assess the efficacy of WT in FAP patients. Ten FAP patients were randomly assigned to receive either WT or placebo for 6 months. Colonoscopies were performed at baseline and after 6 months. The polyp number and size, as well as the cumulative polyp burden, were assessed. No differences were noted between the groups in terms of changes from the baseline's polyp number, size, or burden. However, stratifying the data according to the right vs. left colon indicated a decrease in the median polyp number (from 5.5 to 1.5, p = 0.06) and polyp burden (from 24.25 mm to 11.5 mm, p = 0.028) in the left colon of the patients in the WT group. The adjusted left polyp number and burden in the WT arm were lower by 5.39 (p = 0.034) and 14.68 mm (p = 0.059), respectively. Whether WT can be used to reduce the polyp burden of patients with predominantly left-sided polyps remains to be seen; thus, further larger prospective trials are required.


Myopic hydrogel keratophakia: preliminary report.
Myopic hydrogen keratophakia offers several potential advantages over existing forms of corneal refractive surgery. Because no tissue lathing is required, neither donor tissue nor complex lathing equipment is necessary. Theoretically, hydrogen lens implants with precisely determined and verifiable parameters can be obtained in limitless supply. The surgical effect can be either modified or reversed, if clinically indicated. In this preliminary report, myopic hydrogel implants, with powers between -5 diopters and -20 diopters, were placed in nonhuman primate corneas. Corneascopic analysis showed significant flattening in all instances, and about 70% of the anticipated correction was actually observed. Operative complications were infrequent and generally resulted from traumatic wound dehiscence. Myopic hydrogel keratophakia has tremendous clinical potential, but requires further experimental testing as to safety and efficacy.


Binaural Interaction Effects of 30-50 Hz Auditory Steady State Responses.
Auditory stimuli modulated by modulation frequencies within the 30 to 50 Hz region evoke auditory steady state responses (ASSRs) with high signal to noise ratios in adults, and can be used to determine the frequency-specific hearing thresholds of adults who are unable to give behavioral feedback reliably. To measure ASSRs as efficiently as possible a multiple stimulus paradigm can be used, stimulating both ears simultaneously. The response strength of 30 to 50Hz ASSRs is, however, affected when both ears are stimulated simultaneously. The aim of the present study is to gain insight in the measurement efficiency of 30 to 50 Hz ASSRs evoked with a 2-ear stimulation paradigm, by systematically investigating the binaural interaction effects of 30 to 50 Hz ASSRs in normal-hearing adults. ASSRs were obtained with a 64-channel EEG system in 23 normal-hearing adults. All participants participated in one diotic, multiple dichotic, and multiple monaural conditions. Stimuli consisted of a modulated one-octave noise band, centered at 1 kHz, and presented at 70 dB SPL. The diotic condition contained 40 Hz modulated stimuli presented to both ears. In the dichotic conditions, the modulation frequency of the left ear stimulus was kept constant at 40 Hz, while the stimulus at the right ear was either the unmodulated or modulated carrier. In case of the modulated carrier, the modulation frequency varied between 30 and 50 Hz in steps of 2 Hz across conditions. The monaural conditions consisted of all stimuli included in the diotic and dichotic conditions. Modulation frequencies ≥36 Hz resulted in prominent ASSRs in all participants for the monaural conditions. A significant enhancement effect was observed (average: ~3 dB) in the diotic condition, whereas a significant reduction effect was observed in the dichotic conditions. There was no distinct effect of the temporal characteristics of the stimuli on the amount of reduction. The attenuation was in 33% of the cases >3 dB for ASSRs evoked with modulation frequencies ≥40 Hz and 50% for ASSRs evoked with modulation frequencies ≤36 Hz. Binaural interaction effects as observed in the diotic condition are similar to the binaural interaction effects of middle latency responses as reported in the literature, suggesting that these responses share a same underlying mechanism. Our data also indicated that 30 to 50 Hz ASSRs are attenuated when presented dichotically and that this attenuation is independent of the stimulus characteristics as used in the present study. These findings are important as they give insight in how binaural interaction affects the measurement efficiency. The 2-ear stimulation paradigm of the present study was, for the most optimal modulation frequencies (i.e., ≥40 Hz), more efficient than a 1-ear sequential stimulation paradigm in 66% of the cases.


The use of electrochemical impedance spectroscopy (EIS) in the evaluation of the electrochemical properties of a microbial fuel cell.
Electrochemical impedance spectroscopy (EIS) has been used to determine several electrochemical properties of the anode and cathode of a mediator-less microbial fuel cell (MFC) under different operational conditions. These operational conditions included a system with and without the bacterial catalyst and EIS measurements at the open-circuit potential of the anode and the cathode or at an applied cell voltage. In all cases the impedance spectra followed a simple one-time-constant model (OTCM) in which the solution resistance is in series with a parallel combination of the polarization resistance and the electrode capacitance. Analysis of the impedance spectra showed that addition of Shewanella oneidensis MR-1 to a solution of buffer and lactate greatly increased the rate of the lactate oxidation at the anode under open-circuit conditions. The large decrease of open-circuit potential of the anode increased the cell voltage of the MFC and its power output. Measurements of impedance spectra for the MFC at different cell voltages resulted in determining the internal resistance (R(int)) of the MFC and it was found that R(int) is a function of cell voltage. Additionally, R(int) was equal to R(ext) at the cell voltage corresponding to maximum power, where R(ext) is the external resistance that must be applied across the circuit to obtain the maximum power output.


Top-down proteomic analysis by MALDI-TOF profiling: Concentration-independent biomarkers.
Although numerous protein biomarkers have been correlated with advanced disease states, no new clinical assays have been developed. Goals often anticipate disease-specific protein changes that exceed values among healthy individuals, a property common to acute phase reactants. This review considers somewhat different approaches. It focuses on intact protein isoform ratios that present a biomarker without change in the total concentration of the protein. These will seldom be detected by peptide level analysis or by most antibody-based assays. For example, application of an inexpensive method to large sample groups resulted in observation of several polymorphisms, including the first structural polymorphism of apolipoprotein C1. Isoform distribution of this protein was altered and was eventually linked to increased obesity. Numerous other protein isoforms included C- and N-terminal proteolysis, changes of glycoisoform ratios and certain types of sulfhydryl oxidation. While many of these gave excellent statistical correlation with advanced disease, clinical utility was not apparent. More important may be that protein isoform ratios were very stable in each individual. Diagnosis by longitudinal analysis of the same individual might increase sensitivity of protein biomarkers by 20-fold or more. Protein changes that exceed the range of values found among healthy individuals may be uncommon.


Effects of roundabout on growth cone dynamics, filopodial length, and growth cone morphology at the midline and throughout the neuropile.
roundabout (robo) encodes an axon guidance receptor that controls midline crossing in the Drosophila CNS. In robo mutants, axons that normally project ipsilaterally can cross and recross the midline. Growth cones expressing Robo are believed to be repelled from the midline by the interaction of Robo and its ligand Slit, an extracellular protein expressed by the midline glia. To help understand the cellular basis for the midline repulsion mediated by Robo, we used time-lapse observations to compare the growth cone behavior of the ipsilaterally projecting motorneuron RP2 in robo and wild-type embyros. In wild-type embryos, filopodia can project across the midline but are quickly retracted. In robo mutants, medial filopodia can remain extended for longer periods and can develop into contralateral branches. In many cases RP2 produces both ipsilateral and contralateral branches, both of which can extend into the periphery. The growth cone also exhibits longer filopodia and more extensive branching both at the midline and throughout the neuropile. Cell injections in fixed stage 13 embryos confirmed and quantified these results for both RP2 and the interneuron pCC. The results suggest that Robo both repels growth cones at the midline and inhibits branching throughout the neuropile by promoting filopodial retraction.


[Dieterich's Disease--the rare aseptic necrosis of the metacarpal head].
The rare diagnosis of the Dieterich's disease at the head of the metacarpal III is presented on the case of a 19-year-old female patient. While aseptic bone necroses at the hand skeleton in handsurgical special departments are not rare and diagnostics and choice of the right treatment are not difficult, there are quite rare findings, which are not commonly known. Dieterich's disease finds precipitation in the literature in a handful of articles, mostly case reports. Dieterich saw among 8 patients 7 women, with a distribution of 7 concerned metacarpal bone III and one metacarpal bone IV. A preference of the female sex or the metacarpal bone III cannot be derived from it. Aseptic necroses at the hand are rarer than at the foot skeleton. Clinically, a swelling at the extensor side of the finger basic joint can exist with movement restriction, occasionally is the hand over it slightly turned red. Mechanical load aggravates the complaints. The clinical aspect, X-ray and therapy options are differentially presented and discussed with consideration of the specific literature.


A novel R3 MYB transcriptional repressor associated with the loss of floral pigmentation in Iochroma.
Losses of floral pigmentation represent one of the most common evolutionary transitions in flower color, yet the genetic basis for these changes has been elucidated in only a handful of cases. Here we used crossing studies, bulk-segregant RNA sequencing, phylogenetic analyses and functional tests to identify the gene(s) responsible for the transition to white flowers in Iochroma loxense. Crosses between I. loxense and its blue-flowered sister species, I. cyaneum, suggested that a single locus controls the flower color difference and that the white allele causes a nearly complete loss of pigmentation. Examining sequence variation across phenotypic pools from the crosses, we found that alleles at a novel R3 MYB transcription factor were tightly associated with flower color variation. This gene, which we term MYBL1, falls into a class of MYB transcriptional repressors and, accordingly, higher expression of this gene is associated with downregulation of multiple anthocyanin pigment pathway genes. We confirmed the repressive function of MYBL1 through stable transformation of Nicotiana. The mechanism underlying the evolution of white flowers in I. loxense differs from that uncovered in previous studies, pointing to multiple mechanisms for achieving fixed transitions in flower color intensity.


Charge and spin dynamics in a two-dimensional electron gas.
A number of time-resolved optical experiments probing and controlling the spin and charge dynamics of the high-mobility two-dimensional electron gas in a GaAs/AlGaAs heterojunction are discussed. These include time-resolved reflectivity, luminescence, transient grating, magneto-optical Kerr effect, and electro-optical Kerr effect experiments. The optical experiments provide information on the carrier lifetimes and spin dephasing times, as well as on the carrier diffusion coefficient which directly gives the charge mobility. A combination of the two types of Kerr experiment proves to be useful in extracting both the carrier lifetimes and spin dephasing times in a single experiment.


Risk assessment of consumer spray products using in vitro lung surfactant function inhibition, exposure modelling and chemical analysis.
Consumer spray products release aerosols that can potentially be inhaled and reach the deep parts of the lungs. A thin layer of liquid, containing a mixture of proteins and lipids known as lung surfactant, coats the alveoli. Inhibition of lung surfactant function can lead to acute loss of lung function. We focused on two groups of spray products; 8 cleaning and 13 impregnation products, and in the context of risk assessment, used an in vitro method for assessing inhibition of lung surfactant function. Original spray-cans were used to generate aerosols to measure aerodynamic particle size distribution. We recreated a real-life exposure scenario to estimate the alveolar deposited dose. Most impregnation products inhibited lung surfactant function at the lowest aerosolization rate, whereas only two cleaning products inhibited function at the highest rates. We used inhibitory dose and estimated alveolar deposition to calculate the margin of safety (MoS). The MoS for the inhibitory products was ≤1 for the impregnation products, while much larger for the cleaning products (>880). This risk assessment focused on the risk of lung surfactant function disruption and provides knowledge on an endpoint of lung toxicity that is not investigated by the currently available OECD test guidelines.


Glomerular architectural changes after a two-hour infusion of norepinephrine.
Alterations in glomerular architecture have been suggested to play a role in the pathogenesis of several models of acute renal failure. In this study, mongrel dogs were subjected to an intrarenal infusion of norepinephrine for 2 hours. Light microscopy and scanning and transmission electron microscopy were used to describe glomerular architecture 2 days after the initial norepinephrine infusion. In addition, scanning electron microscopy was used to quantitate the percentage of "abnormal areas" in glomerular capillary-loop morphology in both norepinephrine-infused kidneys and the contralateral control kidneys. Alterations in glomerular structure in these experiments appeared to be much less extensive than previously reported. A variable amount of glomerular pedical shape simplification was seen, which involved about 15% of the capillary loop. Quantitative evaluation revealed abnormal morphology of 15.2% +/- 0.6% of the glomerular capillary loop in the norepinephrine-infused kidneys, compared to 2.9% +/- 0.4 abnormal loop structure in the contralateral control kidneys (P less than 0.001). It is concluded that alterations in glomerular structure are not extensive in this model.


AvrE1 and HopR1 from Pseudomonas syringae pv. actinidiae are additively required for full virulence on kiwifruit.
Pseudomonas syringae pv. actinidiae ICMP 18884 biovar 3 (Psa3) produces necrotic lesions during infection of its kiwifruit host. Bacterial growth in planta and lesion formation are dependent upon a functional type III secretion system (T3S), which translocates multiple effector proteins into host cells. Associated with the T3S locus is the conserved effector locus (CEL), which has been characterized and shown to be essential for the full virulence in other P. syringae pathovars. Two effectors at the CEL, hopM1 and avrE1, as well as an avrE1-related non-CEL effector, hopR1, have been shown to be redundant in the model pathogen P. syringae pv. tomato DC3000 (Pto), a close relative of Psa. However, it is not known whether CEL-related effectors are required for Psa pathogenicity. The Psa3 allele of hopM1, and its associated chaperone, shcM, have diverged significantly from their orthologs in Pto. Furthermore, the CEL effector hopAA1-1, as well as a related non-CEL effector, hopAA1-2, have both been pseudogenized. We have shown that HopM1 does not contribute to Psa3 virulence due to a truncation in shcM, a truncation conserved in the Psa lineage, probably due to the need to evade HopM1-triggered immunity in kiwifruit. We characterized the virulence contribution of CEL and related effectors in Psa3 and found that only avrE1 and hopR1, additively, are required for in planta growth and lesion production. This is unlike the redundancy described for these effectors in Pto and indicates that these two Psa3 genes are key determinants essential for kiwifruit bacterial canker disease.


GM1 ganglioside exerts protective effects against glutamate-excitotoxicity via its oligosaccharide in wild-type and amyotrophic lateral sclerosis motor neurons.
Alterations in glycosphingolipid metabolism have been linked to the pathophysiological mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Accordingly, administration of GM1, a sialic acid-containing glycosphingolipid, is protective against neuronal damage and supports neuronal homeostasis, with these effects mediated by its bioactive component, the oligosaccharide head (GM1-OS). Here, we add new evidence to the therapeutic efficacy of GM1 in ALS: Its administration to WT and SOD1G93A motor neurons affected by glutamate-induced excitotoxicity significantly increased neuronal survival and preserved neurite networks, counteracting intracellular protein accumulation and mitochondria impairment. Importantly, the GM1-OS faithfully replicates GM1 activity, emphasizing that even in ALS the protective function of GM1 strictly depends on its pentasaccharide.


Isolation and characterization of the high-density lipoproteins from the hemolymph and ovary of the penaeid shrimp Penaeus semisulcatus (de Haan): apoproteins and lipids.
The high-density lipoproteins (HDLs) found in the male and female hemolymph of Penaeus semisulcatus de Haan were isolated by NaBr (1.22 g/ml) followed by sucrose gradient (5-25%) ultracentrifugation. The male HDL contained one protein, lipoprotein 1 (LP1), composed of one 110-kDa peptide subunit. The female HDL contained two proteins: 1) the LP1 that was immunoidentical to the male LP1 and was similarly composed of one 110-kDa peptide subunit and 2) vitellogenin (Vg), reacting positively with the rabbit antiserum generated against vitellin (Vt) that was isolated from vitellogenic ovaries. Both Vg and Vt consisted mainly of three polypeptide subunits (200, 120, and 80 kDa) as revealed by denatured PAGE and Western blot. The LP1 from males or females did not react with the Vt rabbit antiserum. Similarly, Vg and Vt did not react with the rabbit antiserum prepared against LP1. Phospholipids (PL) constituted 71-76% of the total lipids in the hemolymph and HDLs of both male and female hemolymph. Cholesterol (Ch) amounted to 17-20%, and small amounts (5%) of diacylglycerols (DAG) were also carried by these HDLs. Both the PL and DAG contained highly unsaturated fatty acids (20:5 omega 3 and 22:6 omega 3) that are transported from the food or hepatopancreas to the tissues, including the vitellogenic ovaries in females. In the present study we show for the first time the separate lipid composition of female LP1 and Vg and compare them with the lipids attached to the Vt. Vg had a lower lipid content than LP1 (540 and 1089 mg/g protein, respectively). Differences were also found in the relative abundance of PL, Ch, and DAG classes in the LP1 in comparison with Vg. Furthermore, small amounts (approximately 3.8%) of triacylglycerols (TAG) were found only in the hemolymph of vitellogenic females, and they were associated with the Vg. Although Vg and Vt were composed of similar polypeptides, their lipid composition was different Vt, in contrast to Vg, carried considerable amounts of TAG (approximately 22%) and only trace amounts of DAG. The significance of the TAG in the hemolymph of vitellogenic females is not known, and the functional relationship between Vg and Vt requires future extensive studies. Lipids were not detected in hemocyanin that was purified from clotted hemolymph.


A comprehensive review of the treatment and management of Charcot spine.
Charcot spine arthropathy (CSA), a result of reduced afferent innervation, is an occurrence of Charcot joint, a progressive, degenerative disorder in vertebral joints, related mostly to spinal cord injury. The repeated microtrauma is a result of a lack of muscle protection and destroys cartilage, ligaments, and disc spaces, leading to vertebrae destruction, joint instability, subluxation, and dislocation. Joint destruction compresses nerve roots, resulting in pain, paresthesia, sensory loss, dysautonomia, and spasticity. CSA presents with back pain, spinal deformity and instability, and audible spine noises during movement. Autonomic dysfunction includes bowel and bladder dysfunction. It is slowly progressive and usually diagnosed at a late stage, usually, on average, 20 years after the first initial insult. Diagnosis is rarely clinical related to the nature of nonspecific symptoms and requires imaging with computed tomography (CT) and magnetic resonance imaging (MRI). Conservative management focuses on the prevention of fractures and the progression of deformities. This includes bed rest, orthoses, and braces. These could be useful in elderly or frail patients who are not candidates for surgical treatment, or in minimally symptomatic patients, such as patients with spontaneous fusion leading to a stable spine. Symptomatic treatment is offered for autonomic dysfunction, such as anticholinergics for bladder control. Most patients require surgical treatment. Spinal fusion is achieved with open, minimally-open (MOA) or minimally-invasive (MIS) approaches. The gold standard is open circumferential fusion; data is lacking to determine the superiority of open or MIS approaches. Patients usually improve after surgery; however, the rarity of the condition makes it difficult to estimate outcomes. This is a review of the latest and seminal literature about the treatment and chronic management of Charcot spine. The review includes the background of the syndrome, clinical presentation, and diagnosis, and compares the different treatment options that are currently available.


[The vaccination of medical personnel as the most important link in the prevention of viral hepatitis B].
The epidemiological importance of prophylaxis of virus hepatitis B among medical personnel of therapeutic-preventive establishments is caused by often revealing of infecting markers in various groups of the population and patients and the chronization of infectious process, the peculiarities of complications, the outcomes of hepatitis and the character of ways of transfer of the virus. The authors have established non-uniformity of the frequency of revealing of infecting markers by virus hepatitis B in blood of medical personnel of various department of the hospital, have described results of immunological efficiency of the domestic vaccine hepatitis B, produced by firm "Kombitech Ltd." (Russia).


Repeated West Nile virus epidemic transmission in Kern County, California, 2004-2007.
West Nile virus (WNV) has remained epidemic in Kern County, CA, since its introduction in 2004 through 2007 when the human case annual incidence increased from 6-8 to 17 per 100,000, respectively. The 2007 increase in human infection was associated with contradicting surveillance indicators, including severe drought, warm spring but cool summer temperature anomalies, decreased rural and urban mosquito abundance but increased early season infection in urban Culex quinquefasciatus Say, moderate avian "herd immunity," and declines in the catch of competent (western scrub-jay and house finch) and noncompetent (California quail and mourning dove) avian species. The decline in these noncompetent avian hosts may have increased contact with competent avian hosts and perhaps humans. The marked increase in home foreclosures and associated neglected swimming pools increased urban mosquito production sites, most likely contributing to the urban mosquito population and the WNV outbreak within Bakersfield. Coalescing five surveillance indicators into a risk assessment score measured each half month provided 2- to 6-wk early warning for emergency planning and was followed consistently by the onset of human cases after reaching epidemic conditions. St. Louis encephalitis virus (SLEV) antibody was detected rarely in wild birds but not mosquitoes or sentinel chickens, indicating that previously infected birds were detected in Kern County, but SLEV reintroduction was not successful. In contrast, western equine encephalitis virus (WEEV) was detected during 3 of 5 yr in Culex tarsalis Coquillett, sentinel chickens, and wild birds, but failed to amplify to levels where tangential transmission was detected in Aedes mosquitoes or humans. A comparison of transmission patterns in Kern County to Coachella Valley in the southeastern desert of California showed the importance of mosquito phenology and spatial distribution, corvids, or other avian "super spreaders" and anthropogenic factors in WNV epidemiology.


Investigating the addition of oral HIV self-tests among populations with high testing coverage - Do they add value? Lessons from a study in Khayelitsha, South Africa.
HIV self-testing (HIVST) offers a useful addition to HIV testing services and enables individuals to test privately. Despite recommendations to the contrary, repeat HIV testing is frequent among people already on anti-retroviral treatment (ART) and there are concerns that oral self-testing might lead to false negative results. A study was conducted in Khayelitsha, South Africa, to assess feasibility and uptake of HIVST and linkage-to-care following HIVST. Participants were recruited at two health facilities from 1 March 2016 to 31 March 2017. People under 18 years, or with self-reported previously-diagnosed HIV infection, were excluded. Participants received an OraQuick Rapid HIV-1/2 Antibody kit, and reported their HIVST results by pre-paid text message (SMS) or by returning to the facility. Those not reporting within 7 days were contacted by phone. Electronic and paper-based clinical and laboratory records were retrospectively examined for all participants to identify known HIV outcomes, after matching for name, date of birth, and sex. These findings were compared with self-reported HIVST results where available. Of 639 participants, 401 (62.8%) self-reported a negative HIVST result, 27 (4.2%) a positive result, and 211 (33.0%) did not report. The record search identified that of the 401 participants self-reporting a negative HIVST result, 19 (4.7%) were already known to be HIV positive; of the 27 self-reporting positive, 12 (44%) were known HIV positive. Overall, records showed 57/639 (8.9%) were HIV positive of whom 39/57 (68.4%) had previously-diagnosed infection and 18/57 (31.6%) newly-diagnosed infection. Of the 428 participants who self-reported a result, 366 (85.5%) reported by SMS. HIVST can improve HIV testing uptake and linkage to care. SMS is acceptable for reporting HIVST results but negative self-reports by participants may be unreliable. Use of HIVST by individuals on ART is frequent despite recommendations to the contrary and its implications need further consideration.


Daptomycin in endocarditis and bacteraemia: a British perspective.
Assessment of the place of daptomycin in the treatment of endocarditis and bacteraemia requires assimilation of data from one open-label randomized comparative clinical trial sized for equivalence, from registry data and from case reports. Selected relevant animal models and in vitro data are also considered in an effort to produce an integrated assessment of the current place of daptomycin in treatment. The evidence for the use of daptomycin is best in Staphylococcus aureus bacteraemia and endocarditis, but also includes some data on infections due to Enterococcus spp., especially if vancomycin-resistant. The emergence of resistance in a minority of patients on current dose regimens may mean that trials have to be repeated with higher doses, or the drug used in a combined therapy where rifampicin may be the best choice. In general, equivalence to comparator antibiotic regimens and a correlation for in vitro and in vivo findings have been demonstrated, but there are important gaps in the clinical data including a comparative equivalence trial in streptococcal and enterococcal endocarditis. Clinical benefit might be anticipated, but has not been proved, over aminoglycoside-containing regimens, and economic assessments are critical in the decision as to when and how daptomycin is deployed.


Guasha-induced hepatoprotection in chronic active hepatitis B: a case study.
Heme oxygenase-1 (HO-1) has demonstrated hepatoprotective effect in animal hepatitis models. HO-1 was also reported to be upregulated with Guasha, an ancient therapeutic technique which applies instrument assisted press-stroking to treat many disorders. We report a case on the changes of liver function, plasma HO-1 and T-helper (Th) cytokine balance in a chronic active hepatitis B carrier before and after Guasha. The patient presented with increased activities of liver enzymes (ALT and AST), indicating inflammatory damage in liver before Guasha. Forty-eight hours after receiving Guasha, the patient showed changes in a number of serum markers: a decline of liver enzymes (ALT and AST) indicating reduced chronic inflammation, an elevated plasma HO-1, and a modulation of T-helper (Th)1/Th2 balance. Guasha was shown to transiently reduce the inflammatory markers of liver injury in human, together with an enhancement of HO-1 which might be responsible for the hepatoprotective action.


Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy.
Treatment initiation with integrase strand transfer inhibitors (INSTIs) has been associated with excess weight gain. Whether similar gains are seen after switch to INSTIs among virologically suppressed persons is less clear. We assessed pre/post-INSTI weight changes from AIDS Clinical Trials Group participants (A5001 and A5322). Participants who were in follow-up from 1997-2017 and switched to INSTI-based antiretroviral regimens were included. Piecewise linear mixed-effects models adjusting for age, sex, race/ethnicity, baseline BMI, nadir and current CD4+ T-cell count, smoking, diabetes and follow-up time with suppressed HIV-1 RNA examined weight and waist circumference change before and after first switch to INSTIs. Linear spline models with a single knot at time of switch accounted for nonlinear trends. The 972 participants who switched to INSTIs were 81% male and 50% nonwhite with a median age at switch of 50 years, CD4+ T-cell count 512 cells/μL, and BMI 26.4 kg/m2. Restricting to persons with suppressed HIV-1 RNA at switch (n = 691), women, blacks, and persons ≥60 years experienced greater weight gain in the 2 years after versus before switch. In adjusted models, white or black race, age ≥60, and BMI ≥30 kg/m2 at switch were associated with greater weight gain following switch among women; age ≥60 was the greatest risk factor among men. Trends for waist circumference were similar. Yearly weight gain increased following switch to INSTIs, particularly for women, blacks, and persons aged ≥60. Concomitant increases in waist circumference suggest that this weight gain is associated with an increase in fat mass.


Increased cardiovascular response to static contraction of larger muscle groups.
The purpose of this study was to investigate the influence of the size of the active muscle mass on the cardiovascular response to static contraction. Twelve male subjects performed one-arm handgrip (HG), two-leg extension (LE), and a "dead-lift" maneuver (DL) in a randomly assigned order for 3 min at 30% of maximal voluntary contraction. O2 uptake (VO2), heart rate (HR), and mean intra-arterial blood pressure (MABP) were measured at rest and, in addition to absolute tension exerted, throughout contraction. There was a direct relationship between the size of the active muscle mass and the magnitude of the increases in VO2, HR, and MABP, even though all contractions were performed at the same relative intensity. Tension, VO2, HR, and MABP increased progressively from HG to LE to DL. It was concluded that at the same percentage of maximal voluntary contraction, the magnitude of the cardiovascular response to isometric exercise is directly influenced by the size of the contracting muscle mass.


Obstacle course runs: review of acquired injuries and illnesses at a series of Canadian events (RACE).
The growing popularity of obstacle course runs (OCRs) has led to significant concerns regarding their safety. The influx of injuries and illnesses in rural areas where OCRs are often held can impose a large burden on emergency medical services (EMS) and local EDs. Literature concerning the safety of these events is minimal and mostly consists of media reports. We sought to characterise the injury and illness profile of OCRs and the level of medical care required. This study analysed OCR events occurring in eight locations across Canada from May to August 2015 (total 45 285 participants). Data were extracted from event medical charts of patients presenting to the onsite medical team, including injury or illness type, onsite treatment and disposition. There were 557 race participants treated at eight OCR events (1.2% of all participants). There were 609 medical complaints in total. Three quarters of injuries were musculoskeletal in nature. Eighty-nine per cent returned to the event with no need for further medical care. The majority of treatments were completed with first aid and basic medical equipment. Eleven patients (2% of patients) required transfer to hospital by EMS for presentations including fracture, dislocation, head injury, chest pain, fall from height, and abdominal pain. We found that 1.2% of race participants presented to onsite medical services. The majority of complaints were minor and musculoskeletal in nature. Only 2% of those treated were transferred to hospital through EMS. This is consistent with other types of mass gathering events.


Non-small cell lung cancer and central nervous system metastases: should we be using prophylactic cranial irradiation?
Central nervous system (CNS) failure in patients with locally advanced non-small cell; lung cancer (LA-NSCLC) is a common and debilitating problem. Standard follow-up after local regional therapy does not include routine radiologic evaluation of the brain. Imaging is performed at the onset of symptoms followed by palliative therapy for CNS failure. Some investigators support regular screening with therapy for failures before the onset of symptoms. This alternative may decrease the impact of CNS failures and lengthen survival. Other investigators have shown that prophylactic cranial irradiation (PCI) for LA-NSCLC decreases the incidence of CNS failures. The potential survival, quality of life, and neuropsychological advantage or disadvantage of these two approaches has not been systematically studied. This article will review the problem of CNS failures in patients with LA-NSCLC and the potential risks and benefits of close observation and PCI. The necessity of conducting an ambitious study evaluating the potential survival advantage of PCI will be discussed.