Risk factors for contact lens complications in US clinical practices.
To determine significant risk factors for any inflammatory and infectious events with soft contact lenses (SCL) in a large retrospective clinical chart review. Charts of patients who presented for SCL care from October 2005 through March 2006 were reviewed and observed for a potential of at least 2 years. Charts from those with office visits involving an event-requiring pharmacologic treatment and/or interruption of SCL wear were scanned and later adjudicated by a masked panel. Significant factors from a univariate analysis were included in a multivariate analysis for all events and subcategories of events separately. Overnight wear was not consistently recorded and was not analyzed. Charts from 1276 SCL wearers comprised 4120 visits and 1454 years of SCL wear (2908 eye/yr) and included 306 events of interest in 228 patients. In a multivariate analysis, age <25 years was significantly associated with presenting any event, inflammatory events, and infectious events that may or may not be CL-related [incidence rate ratio (IRR) = 1.3; 95% CI, 1.0 to 1.7; 2.6X, 1.5 to 4.6; and 2.0X, 1.2 to 3.3, respectively]. Ametropia >5.00 D increased risk of any event (IRR = 1.5; 1.2 to 1.9) and for other infectious events (IRR = 1.9; 1.2 to 3.2). Use of daily disposable lenses associated with lid irritation (IRR = 4.5; 2.1 to 9.8) but was not significantly associated with any other type of events. New and hydrogel lens wearers had a lower incidence of all event types (IRR = 0.07; 0.01 to 0.46 and 0.77; 0.59 to 0.99, respectively). Eighty-two percent of these SCL wearers did not present with any complications during the observation period >2 years. The risk factors for inflammatory and infectious events among SCL wearers in clinical practice are similar to those reported in prospective clinical trials. High ametropia and age <25 years are the risk factors that impact the most types of events.


Early prediction of COVID-19-associated acute kidney injury: Are serum NGAL and serum Cystatin C levels better than serum creatinine?
Coronavirus disease-2019 (COVID-19) is associated with a high risk of acute kidney injury (AKI), often requiring renal replacement therapy (RRT). Serum Cystatin C (sCysC) and serum Neutrophil Gelatinase-Associated Lipocalin (sNGAL) are emerging biomarkers for kidney injury, and were suggested to be superior to serum creatinine (sCr) in several clinical settings. Moreover, elevated sCysC is associated with disease severity and mortality in COVID-19. We aimed to assess the utility of sCysC and sNGAL for predicting COVID-19-associated AKI, need for RRT, and need for intensive care unit (ICU) admission, when measured at presentation to the emergency department (ED). Patients presenting to the ED with laboratory-confirmed COVID-19 were included. The primary outcome was development of COVID-19-associated AKI, while the secondary outcomes were need for RRT and ICU admission. Among 52 COVID-19 patients, 22 (42.3%) developed AKI with 8/22 (36.4%) requiring RRT. Both sCr and sCysC demonstrated excellent performance for predicting AKI (AUC, 0.86 and 0.87, respectively) and need for RRT (AUC, 0.94 and 0.95, respectively). sNGAL displayed acceptable performance for predicting AKI (AUC, 0.81) and need for RRT (AUC, 0.87). SCr and sCysC measured at ED presentation are both highly accurate predictors of AKI and need for RRT, whereas sNGAL demonstrated adequate diagnostic performance. While sCyC was previously shown to be superior to sCr as a diagnostic biomarker of kidney injury in certain etiologies, our findings demonstrate that sCr is comparable to sCyC in the context of predicting COVID-19-associated AKI. Given the high sensitivity of these biomarkers for predicting the need for RRT, and as sCysC is associated with mortality in COVID-19 patients, we recommend their measurement for enabling risk stratification and early intervention.


The influence of a fast ramp rate on peak cardiopulmonary parameters during arm crank ergometry.
The influence of a very fast ramp rate on cardiopulmonary variables at ventilatory threshold and peak exercise during a maximal arm crank exercise test has not been extensively studied. Considering that short arm crank tests could be sufficient to achieve maximal oxygen consumption (VO₂), it would be of practical interest to explore this possibility. Thus, this study aimed to analyse the influence of a fast ramp rate (20 W min⁻¹) on the cardiopulmonary responses of healthy individuals during a maximal arm crank ergometry test. Seventeen healthy individuals performed maximal cardiopulmonary exercise tests (Ultima CardiO2; Medical Graphics Corporation, St Louis, USA) in arm ergometer (Angio, LODE, Groningen, The Netherlands) following two protocols in random order: fast protocol (increment: 2 w/6 s) and slow protocol (increment: 1 w/6 s). The fast protocol was repeated 60-90 days after the 1st test to evaluate protocol reproducibility. Both protocols elicited the same peak VO₂ (fast: 23.51 ± 6.00 versus slow: 23.28 ± 7.77 ml kg⁻¹ min⁻¹; P = 0.12) but peak power load in the fast ramp protocol was higher than the one in the slow ramp protocol (119 ± 43 versus. 102 ± 39 W, P < 0.001). There was no other difference in ventilatory threshold and peak exercise variables when 1st and 2nd fast protocols were compared. Fast protocol seems to be useful when healthy young individuals perform arm cardiopulmonary exercise test. The usefulness of this protocol in other populations remains to be evaluated.


Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery: An Uncommon Coronary Anomaly With Serious Implications in Adulthood.
A 36-year-old woman was seen with complaints of exertional chest pain and shortness of breath. Her medical history included atrial fibrillation and diabetes. Physical examination was unremarkable except for an irregular cardiac rhythm. Myocardial perfusion imaging revealed the presence of a large area of infarction involving the entire anterior and apical walls and part of the anteroseptal wall with minimal periinfarct ischemia. Computed tomography coronary angiogram revealed an anomalous left main coronary artery arising from the main pulmonary artery. Right and left heart catheterizations demonstrated moderate pulmonary hypertension with a slight step-up in oxygen saturation between the right ventricle and main pulmonary artery. Coronary angiography showed a large tortuous right coronary artery with collaterals to the left anterior descending artery that drained into the main pulmonary artery. She was referred for surgery. This case demonstrates a rare coronary artery anomaly in an adult where survival is dependent on collateral circulation.


ALG12-CDG: novel glycophenotype insights endorse the molecular defect.
Congenital disorders of glycosylation (CDG) are genetic diseases characterized by deficient synthesis (CDG type I) and/or abnormal processing (CDG type II) of glycan moieties linked to protein and lipids. The impact of the molecular defects on protein glycosylation and in turn on the clinical phenotypes of patients with CDG is not yet understood. ALG12-CDG is due to deficiency of ALG12 α1,6-mannosyltransferase that adds the eighth mannose residue on the dolichol-PP-oligosaccharide precursor in the endoplasmic reticulum. ALG12-CDG is a severe multisystem disease associated with low to deficient serum immunoglobulins and recurrent infections. We thoroughly investigated the glycophenotype in a patient with novel ALG12 variants and immunodeficiency. We analyzed serum native transferrin, as first line test for CDG and we profiled serum IgG and total serum N-glycans by a combination of consolidated (N-glycan analysis by MALDI MS) and innovative mass spectrometry-based protocols, such as GlycoWorks RapiFluor N-glycan analysis coupled with LC-ESI MS. Intact serum transferrin showed, as expected for a CDG type I defect, underoccupancy of N-glycosylation sites. Surprisingly, total serum proteins and IgG N-glycans showed some specific changes, consisting in accumulating amounts of definite high-mannose and hybrid structures. As a whole, ALG12-CDG behaves as a dual CDG (CDG-I and II defects) and it is associated with distinct, abnormal glycosylation of total serum and IgG N-glycans. Glycan profiling of target glycoproteins may endorse the molecular defect unraveling the complex clinical phenotype of CDG patients.


Value of having a cytopathologist present during percutaneous fine-needle aspiration biopsy of lung: report of 55 cancer patients and metaanalysis of the literature.
Percutaneous fine-needle aspiration biopsy is an accepted procedure for diagnosing intrathoracic malignant disease. The value of having a cytopathologist present during the procedure was studied with respect to the number of needle passes, the accuracy of the procedure, and complications. A metaanalysis was performed on the combined results of the present and previous series. We analyzed data from 55 adult patients who underwent percutaneous CT-guided fine-needle (22-gauge) aspiration biopsy of the lung for a lesion that either the biopsy or another subsequent invasive procedure showed to be nonlymphomatous and malignant. A cytopathologist was present for the first 25 procedures and not present for the next 30 procedures. When present, the cytopathologist stained the aspirated material with toluidine blue and gave an immediate opinion on the diagnostic adequacy of the specimen based on microscopic evaluation. If appropriate, the radiologist obtained additional biopsy specimens. When a cytopathologist was not present, the radiologist assessed the adequacy of the specimen by gross examination. A metaanalysis was performed of 211 cases from the present study and two previous series with respect to the effect of the presence of a cytopathologist on the diagnostic accuracy of the procedure. Biopsy specimens showed cancer in 25 (100%) of 25 patients when obtained while the cytopathologist was present, and in 24 (80%) of 30 patients when obtained while the cytopathologist was absent (p < .05, Fisher exact test). No significant differences in the number of needle passes performed or in the frequency of pneumothorax when aerated lung was traversed were noted between the two groups. Although two previous studies showed nonsignificant trends toward increased accuracy of thoracic fine-needle aspiration when a cytopathologist participated in the procedure, metaanalysis revealed significantly increased accuracy when a cytopathologist was present (p < .02, Mantel-Haenszel chi 2-test). An accurate diagnosis from fine-needle aspiration biopsy of intrathoracic cancer was more likely when a cytopathologist was present than when not present during the procedure.


Cross-national income inequality: how great is it and what can we learn from it?
In recent years there has been increasing interest in the topic of income distribution in a cross-national context. A secular growth of income inequality has taken place over the past two decades affecting almost every rich nation, matched by the growth in comparable household income inequality data which makes these types of comparisons possible. While clear patterns of disposable income inequality differences are found in both level and trend, we are still a long way from explaining why these differences came about, whether they will continue to grow or stabilize, and what the social consequences of these changes might be.


Mechanisms of motoric cognitive risk-Hypotheses based on a systematic review and meta-analysis of longitudinal cohort studies of older adults.
We aimed to refine the hypothesis that motoric cognitive risk (MCR), a syndrome combining measured slow gait speed and self-reported cognitive complaints, is prognostic of incident dementia and other major causes of morbidity in older age. We propose mechanisms on the relationship between motor and cognitive function and describe a roadmap to validate these hypotheses. We systematically searched major electronic databases from inception to August 2021 for original longitudinal cohort studies of adults aged ≥60 years that compared an MCR group to a non-MCR group with any health outcome. Fifteen cohorts were combined by meta-analysis. Participants with MCR were at an increased risk of cognitive impairment (adjusted hazard ratio [aHR] 1.76, 95% CI 1.49-2.08; I2 = 24.9%), dementia (aHR 2.12, 1.85-2.42; 33.1%), falls (adjusted Relative Risk 1.38, 1.15-1.66; 62.1%), and mortality (aHR 1.49, 1.16-1.91; 79.2%). The prognostic value of MCR is considerable and mechanisms underlying the syndrome are proposed.


Loss of inhibition in sensorimotor networks in focal hand dystonia.
To investigate GABA-ergic receptor density and associated brain functional and grey matter changes in focal hand dystonia (FHD). 18 patients with FHD of the right hand and 18 age and gender matched healthy volunteers (HV) participated in this study. We measured the density of GABA-A receptors using [11C] Flumazenil and perfusion using [15O] H2O. Anatomical images were also used to measure grey matter volume with voxel-based morphometry (VBM). In FHD patients compared to HV, the vermis VI of the right cerebellum and the left sensorimotor cortex had a decrease of Flumazenil binding potential (FMZ-BP), whereas the striatum and the lateral cerebellum did not show significant change. Bilateral inferior prefrontal cortex had increased FMZ-BP and an increase of perfusion, which correlated negatively with disease duration. Only the left sensorimotor cortex showed a decrease of grey matter volume. Impairments of GABAergic neurotransmission in the cerebellum and the sensorimotor cortical areas could explain different aspects of loss of inhibitory control in FHD, the former being involved in maladaptive plasticity, the latter in surround inhibition. Reorganization of the inferior prefrontal cortices, part of the associative network, might be compensatory for the loss of inhibitory control in sensorimotor circuits. These findings suggest that cerebellar and cerebral GABAergic abnormalities could play a role in the functional imbalance of striato-cerebello-cortical loops in dystonia.


JAK2 (V617F) Positive Latent Myeloproliferative Neoplasm Presenting with Splanchnic Vein Thrombosis.
Myeloproliferative neoplasms (MPNs) are chronic clonal hematopoietic stem cell disorders characterized by proliferation of one or more of the granulocytic, red cell or platelet lineages in the bone marrow, with fairly normal maturation, resulting in increase in the leukocyte, erythrocytes and platelets in the blood. They also represent a common cause of splanchnic vein thrombosis (SVT). Herein, we describe a case of SVT as a presenting symptom of latent MPN. The patient has had normal complete blood counts since presentation. 3 ½ years later, she was found to have JAK2 (V617F) mutation and bone marrow biopsy was consistent with MPN. Five years later, her platelet count started to rise. In patients with a first episode of SVT, thrombophilia workup including JAK2 (V617F) mutation is warranted. Anticoagulation with heparin and warfarin is the treatment of choice for SVT.


Sperm transport and storage in the agile antechinus (Antechinus agilis).
This study was an examination of the timing of ejaculation and the dynamics of sperm transport in the female reproductive tract of the agile Antechinus (Antechinus agilis) and the relationship of these parameters to single and multiple matings. Mating in this species is characteristically long compared with that of other mammals, lasting for up to 8-12 h during which time the pair remain locked together. After the first hour of mating, only approximately 40% of males had ejaculated, but by the third hour all males had ejaculated. The total number of spermatozoa extracted from the female tract remained at approximately 30 x 10(3) spermatozoa per side over the next 9 h of copulation. After completion of male/female access (12 h), approximately 56% of spermatozoa extracted were located in the lower isthmic region of the oviduct where specialized sperm storage crypts are located. The number of spermatozoa extracted from the female reproductive tract did not decline over the next 3 days, but there was a change in the distribution of spermatozoa with an increase in the proportion of extracted spermatozoa stored in the lower isthmus (approximately 76%). However, 7 to 14 days after mating, only approximately 30% of the stored spermatozoa ( approximately 9.4 x 10(3) spermatozoa per side) were still present in the isthmus. When females were mated with a second male on a consecutive day, the sperm numbers extracted from the tract were about twice that deposited during single mating, with sperm transport to the lower isthmus occurring over a similar time frame. Although the occurrence of extended copulations in the wild has not yet been confirmed, these laboratory results suggest that similar periods of copulation are likely, since completion of the ejaculation process requires at least 3 h. The extended copulation in A. agilis reduces the possibility of an early second mating, which might interfere with the normal transport and crypt colonization of spermatozoa through competition.


Ultrafast Charge Carrier Dynamics in CuWO4 Photoanodes.
CuWO4 is a ternary metal oxide semiconductor with promising properties for photoelectrochemical (PEC) water splitting and solar light conversion, due to its quite low band gap (2.3 eV) and high stability in an alkaline environment. Aiming at understanding the origin of the relatively low PEC efficiency attained with CuWO4 photoanodes, we here investigate transparent CuWO4 electrodes prepared by a simple solution-based method through the combination of femtosecond transient absorption spectroscopy with electrochemical, PEC, and photochromic characterizations. The very fast recombination dynamics of the charge carriers photogenerated in CuWO4, which is the reason for its low efficiency, is discussed in relation with its PEC performance and with the recently calculated band structure of this material, also in comparison with the behavior of other semiconductor oxides employed in PEC applications, in particular Fe2O3.


Can behavioral sensory processing problems guide us to a better pharmacological management of children with attention deficit hyperactivity disorder?: a case report.
Sensory processing problems in children with attention deficit hyperactivity disorder have been the focus of many studies in recent years. It is obvious that different aspects of sensory problems such as with tactile sensory are involved in attention deficit hyperactivity disorder. However, whether the sensory information process problems can be factors in decision making regarding pharmacological management of children with attention deficit hyperactivity disorder has not been researched. This case report presents two children with attention deficit hyperactivity disorder. The mother of the first patient reported that her child's ability for detecting, identifying, and discriminating smells was very high and more than the other children at this age. As she reported, the child also liked to touch everything and everybody. He experienced nail biting after taking 20mg methylphenidate in single dosage. By decreasing of the dosage, nail biting disappeared in the three trials. The other patient started lip biting about half an hour after taking the first dosage of the medication. It continued for four hours. This report suggests that there is an association between methylphenidate and tactile sensory problems in children with attention deficit hyperactivity disorder. It is possible that methylphenidate induces or exacerbates tactile hyposensitivity. If this assumption is supported in controlled clinical trials, then tactile sensory assessment might help to make decisions for the pharmacological management of children with attention deficit hyperactivity disorder. Further studies should investigate whether attention deficit hyperactivity disorder with sensory processing problems is a phenotype with an overlap between autistic disorders and attention deficit hyperactivity disorder in which stimulants may exacerbate some sensory processing problems. Also, if this is the case, the diagnosis of attention deficit hyperactivity disorder as an exclusionary criterion for pervasive developmental disorder needs to be revised.


CREB coactivators CRTC2 and CRTC3 modulate bone marrow hematopoiesis.
Populations of circulating immune cells are maintained in equilibrium through signals that enhance the retention or egress of hematopoietic stem cells (HSCs) from bone marrow (BM). Prostaglandin E2 (PGE2) stimulates HSC renewal and engraftment through, for example, induction of the cAMP pathway. Triggering of PGE2 receptors increases HSC survival in part via the PKA-mediated induction of the cAMP response element-binding protein (CREB) signaling pathway. PKA stimulates cellular gene expression by phosphorylating CREB at Ser133 and by promoting the dephosphorylation of the cAMP- responsive transcriptional coactivators (CRTCs). We show here that disruption of both CRTC2 and CRTC3 causes embryonic lethality, and that a single allele of either CRTC2 or CRTC3 is sufficient for viability. CRTC2 knockout mice that express one CRTC3 allele (CRTC2/3m mice) develop neutrophilia and splenomegaly in adulthood due to the up-regulation of granulocyte-colony stimulating factor (G-CSF); these effects are reversed following administration of neutralizing anti-G-CSF antiserum. Adoptive transfer of CRTC2/3m BM conferred the splenomegaly/neutrophilia phenotype in WT recipients. Targeted disruption of both CRTC2 and CRTC3 in stromal cells with a mesenchymal Prx1-Cre transgene also promoted this phenotype. Depletion of CRTC2/3 was found to decrease the expression of Suppressor of Cytokine Signaling 3 (SOCS3), leading to increases in STAT3 phosphorylation and to the induction of CEBPβ, a key regulator of the G-CSF gene. As small molecule inhibition of JAK activity disrupted CEBPβ induction and reduced G-CSF expression in CRTC2/3m stromal cells, our results demonstrate how cross-coupling between the CREB/CRTC and JAK/STAT pathways contributes to BM homeostasis.


Analysis of fluorogenic Smith degradation products of 7-(1,3-disulfonaphtyl)amino-disaccharides for linkage position analysis of carbohydrates.
The linkage position of a glycosidic bond to the reducing-end residue of a pyridylamino (PA-) sugar can be determined sensitively by Smith degradation and HPLC [K. Omichi and S. Hase, (1994) J. Biochem. 115, 429-434]. With the aim of enhancing the sensitivity of this method of linkage position analysis to the fmol-level, use of the 7-(1,3-disulfonaphtyl)amino (DSNA-) group instead of the PA-group as a fluorescent tag was examined. Smith degradation of DSNA-disaccharides with a DSNA-hexose, DSNA-N-acetylglucosamine, or DSNA-N-acetylgalactosamine reducing-end residue was carried out. HPLC and FAB-MS of the fluorogenic Smith degradation products showed that the DSNA-group was stable under the Smith degradation reaction conditions, and that the reaction proceeded in a manner similar to that using PA-disaccharides to give the predicted products. Fluorogenic Smith degradation products specific to the glycosidic linkage position were well separated by reversed-phase HPLC, and were easily assignable by comparing the HPLC elution positions with those of standard compounds. The method was successfully applied to analyzing the structure of an N-linked sugar chain.


Methylomic changes during conversion to psychosis.
The onset of psychosis is the consequence of complex interactions between genetic vulnerability to psychosis and response to environmental and/or maturational changes. Epigenetics is hypothesized to mediate the interplay between genes and environment leading to the onset of psychosis. We believe we performed the first longitudinal prospective study of genomic DNA methylation during psychotic transition in help-seeking young individuals referred to a specialized outpatient unit for early detection of psychosis and enrolled in a 1-year follow-up. We used Infinium HumanMethylation450 BeadChip array after bisulfite conversion and analyzed longitudinal variations in methylation at 411 947 cytosine-phosphate-guanine (CpG) sites. Conversion to psychosis was associated with specific methylation changes. Changes in DNA methylation were significantly different between converters and non-converters in two regions: one located in 1q21.1 and a cluster of six CpG located in GSTM5 gene promoter. Methylation data were confirmed by pyrosequencing in the same population. The 100 top CpGs associated with conversion to psychosis were subjected to exploratory analyses regarding the related gene networks and their capacity to distinguish between converters and non-converters. Cluster analysis showed that the top CpG sites correctly distinguished between converters and non-converters. In this first study of methylation during conversion to psychosis, we found that alterations preferentially occurred in gene promoters and pathways relevant for psychosis, including oxidative stress regulation, axon guidance and inflammatory pathways. Although independent replications are warranted to reach definitive conclusions, these results already support that longitudinal variations in DNA methylation may reflect the biological mechanisms that precipitate some prodromal individuals into full-blown psychosis, under the influence of environmental factors and maturational processes at adolescence.


Non-genetic direct reprogramming and biomimetic platforms in a preliminary study for adipose-derived stem cells into corneal endothelia-like cells.
Cell fate and function can be regulated and reprogrammed by intrinsic genetic program, extrinsic factors and niche microenvironment. Direct reprogramming has shown many advantages in the field of cellular reprogramming. Here we tried the possibility to generate corneal endothelia (CE) -like cells from human adipose-derived stem cells (ADSCs) by the non-genetic direct reprogramming of recombinant cell-penetrating proteins Oct4/Klf4/Sox2 (PTD-OKS) and small molecules (purmorphamine, RG108 and other reprogramming chemical reagents), as well as biomimetic platforms of simulate microgravity (SMG) bioreactor. Co-cultured with corneal cells and decellularized corneal ECM, Reprogrammed ADSCs revealed spherical growth and positively expressing Nanog for RT-PCR analysis and CD34 for immunofluorescence staining after 7 days-treatment of both purmorphamine and PTD-OKS (P-OKS) and in SMG culture. ADSCs changed to CEC polygonal morphology from spindle shape after the sequential non-genetic direct reprogramming and biomimetic platforms. At the same time, induced cells converted to weakly express CD31, AQP-1 and ZO-1. These findings demonstrated that the treatments were able to promote the stem-cell reprogramming for human ADSCs. Our study also indicates for the first time that SMG rotary cell culture system can be used as a non-genetic means to promote direct reprogramming. Our methods of reprogramming provide an alternative strategy for engineering patient-specific multipotent cells for cellular plasticity research and future autologous CEC replacement therapy that avoids complications associated with the use of human pluripotent stem cells.


Interspecific variation in seed size and safe sites in a temperate rain forest.
• The safe site concept could have utility in community ecology if predictive relationships between plant traits and safe site characteristics could be identified. Here we examine the proposal that the nature and relative abundance of safe sites are systematically related to seed size, in an assemblage of 17 woody species in a temperate forest. • We compared the degree of association of seedlings of each species with elevated microsites, and examined life-history correlates of this variation. • Seed size explained 45% of interspecific variation in percentage of seedlings growing on logs and other elevated substrates. Neither specific leaf area nor an index of light requirements gave significant increases in explanatory power. Phylogenetically independent contrasts gave a similar, but weaker, relationship with seed size. Most small-seeded species were overrepresented on elevated microsites, whereas two large-seeded taxa were underrepresented on these substrates. Safe sites of small-seeded species were therefore more spatially restricted than those of large-seeded taxa, as elevated surfaces occupied only 8% of the forest floor. • Safe site differentiation may help to explain the wide range of seed size present within many communities, as well as species coexistence in forests.


Underwater Weighing Familiarization Program for Adults with Prader-Willi Syndrome.
The purpose of the project was to evaluate an underwater weighing (UWW) and residual lung volume (RV) familiarization program developed for adults with Prader-Willi syndrome (PWS). UWW was conducted on 15 adults (10 men, 5 women) with PWS following a UWW familiarization program. Repeated measures ANOVA revealed no difference in percent body fat derived from UWW over the four sessions, F(3, 27) = 0.80, p = .505, with an intraclass reliability coefficient of R = .93. There was, however, a significant difference in RV, F(3, 27) = 5.25, p = .006, with an intraclass reliability coefficient of R = .65. The familiarization program is recommended for implementation prior to measuring percent body fat via UWW. However, predicting the RV may be an easier and more consistent alternative to measuring the RV in adults with PWS.


Rhythm and Blues - Amalie's 152nd session: From psychoanalysis to conversation and metaphor analysis - and back again.
Conversation analysis and psychotherapy process research is an evolving field promising new insights for therapeutic practice. As the specimen case of Amalie, especially her 152nd session, has been investigated using various methods - of which we give a short overview - we offer a new analysis of session 152 based on a new transcription which allows for more detailed listening to the prosodic properties of this analytic dyad. Our findings show a) how analyst and patient co-create their common conversational object called psychoanalysis; b) how a lot of up-to-now not described analytical tools are applied, that can be described as "practices"; c) how a "dance of insight" is enacted by both participants in a common creation making patterns of interaction visible from "both sides"; d) how participants create metaphors as conversational and cognitive tools to reduce the enormous complexity of the analytic exchange and for other purposes; e) that prosodic rhythmicity and other prosodic features are best integrated in a threefold model for analytic conversation consisting of "interaction engine", "talking to" and "talking about" the patient. The study is presented as hypothesis-generating research based on verbal, not statistical data.


Ultrafine and smooth full metal nanostructures for plasmonics.
Full metal various nanostructures with extremely smooth surface, small feature size and high aspect ratio can be fabricated by a template stripping method with EBL-patterned PMMA layer as a template. It is further demonstrated that our method is crucial to obtain clear and abundant plasmonic modes in nanocavities with metal reflectors.


Operative management of massive hernias with associated distended bowel.
Hernia patients with a history of recurrent bowel obstructions, chronic bowel dysmotility, and bowel distension have few options for return to a "normal" life. Return of the bowel and adhesiolysis seems the logical surgical solution, but the return of a swollen distended bowel into the abdominal cavity would put patients at a high risk for the development of abdominal compartment syndrome. Hernia repair with large pieces of mesh under tenuous skin flaps to incorporate the bowel into the abdominal cavity has its own set of devastating complications, including mesh infection, extrusion, and fistula formation. Here we present 4 patients who underwent successful treatment with a combined small bowel resection for volume reduction and simultaneous components separation hernia repair for autogenous closure without mesh. All patients had successful abdominal wall closure without major complications and were tolerating enteral feedings upon discharge. A combined approach of small bowel resection and separation of parts hernia repair is a feasible and successful means for approaching challenging abdominal wall defects with chronically distended bowel. A vicious cycle in which postoperative elevation in intra-abdominal pressure leads to severe systemic consequences can be averted. Moreover, bowel function can be restored and excellent cosmesis achieved, leading to significant improvements in patients' quality of life.


Nitrogen Pretreatment of Growth Substrates for Vacancy-Saturated MoS2.
Two-dimensional transition-metal dichalcogenides (2D TMDCs) are considered promising materials for optoelectronics due to their unique optical and electric properties. However, their potential has been limited by the occurrence of atomic vacancies during synthesis. While post-treatment processes have demonstrated the passivation of such vacancies, they increase process complexity and affect the TMDC's quality. We here introduce the concept of pretreatment as a facile and powerful route to solve the problem of vacancies in MoS2. Low-temperature nitridation of the sapphire substrate prior to growth provides a nondestructive method to MoS2 modification without introducing new processing steps or increasing the thermal budget. Spectroscopic characterization and atomic-resolution microscopy reveal the incorporation of nitrogen from the sapphire surface layer into chalcogen vacancies. The resulting MoS2 with nitrogen-saturated defects shows a decrease in midgap states and more intrinsic doping as confirmed by ab initio calculations and optoelectronic measurements. The demonstrated pretreatment method opens up new routes toward future, high-performance 2D electronics, as evidenced by a 3-fold reduction in contact resistance and a 10-fold improved performance of 2D photodetectors.


[Fatal course of a sequestration crisis in hemoglobin SC disease].
A 14 year-old patient developed severe anemia and splenomegaly 2 days after the onset of a febrile upper airway infection. The hemoglobin concentration had dropped to 1.1 g/dl. Death occurred as consequence of the acute anemia and peripheral circulatory failure. The crisis was caused by an acute splenic sequestration. Hemoglobin SC disease could be identified as the underlying disorder. Hemoglobin SC disease usually has a milder course than sickle cell disease. However the patients may develop the same crisis-like symptoms. Splenic sequestration is caused by the occlusion of the splenic sinuses due to sickled and aggregated erythrocytes with subsequent trapping of large blood volumes and circulatory failure. Regular transfusions and/or splenectomy are recommended to prevent splenic sequestration crisis.


MHC-identical and transgenic cynomolgus macaques for preclinical studies.
Cynomolgus macaques are useful experimental animals that are physiologically and genetically close to humans. We have developed two kinds of experimental usage of cynomolgus macaque: transplantation and disease models. First, we identified certain major histocompatibility complex (MHC) haplotypes including homozygotes and heterozygotes in cynomolgus macaques native to the Philippines, because they have less polymorphism in the MHC than that in other origins such as Vietnam and Indonesia. As a preclinical model of the induced pluripotent stem cell (iPSC) stock project, we established iPSCs from various types of MHC homozygous macaques, which were transplanted into compatible MHC heterozygous macaques, the iPSC stock project was experimentally shown to be effective. Second, to obtain disease models of cynomolgus macaques for studies on regenerative medicine including cell therapies, we established two kinds of genetic technology to modify cynomolgus macaques: transgenic technology and gene editing technology using CRISPR-Cas9. We will establish disease models, such as Alzheimer's disease and progeria (Werner syndrome). In future, we will distribute the MHC-identical cynomolgus monkeys and genetically modified macaques to researchers, especially those engaging in regenerative medicine.


Physical mapping of a commonly deleted region, the site of a candidate tumor suppressor gene, at 12q22 in human male germ cell tumors.
A candidate tumor suppressor gene (TSG) site at 12q22 characterized by a high frequency of loss of heterozygosity (LOH) and a homozygous deletion has previously been reported in human male germ cell tumors (GCTs). In a detailed deletion mapping analysis of 67 normal-tumor DNAs utilizing 20 polymorphic markers mapped to 12q22-q24, we identified the limits of the minimal region of deletion at 12q22 between D12S377 (proximal) and D12S296 (distal). We have constructed a YAC contig map of a 3-cM region of this band between the proximal marker D12S101 and the distal marker D12S346, which contained the minimal region of deletion in GCTs. The map is composed of 53 overlapping YACs and 3 cosmids onto which 25 polymorphic and nonpolymorphic sequence-tagged sites (STSs) were placed in a unique order. The size of the minimal region of deletion was approximately 2 Mb from overlapping, nonchimeric YACs that spanned the region. We also developed a radiation hybrid (RH) map of the region between D12S101 and D12S346 containing 17 loci. The consensus order developed by RH mapping is in good agreement with the YAC STS-content map order. The RH map estimated the distance between D12S101 and D12S346 to be 246 cR8000 and the minimal region of deletion to be 141 cR8000. In addition, four genes that were previously mapped to 12q22 have been excluded as candidate genes. The leads gained from the deletion mapping and physical maps should expedite the isolation and characterization of the TSG at 12q22.


Single photon x-ray detection with a CCD image sensor.
Individual x rays of 5.9 and 22.4 keV have been detected and energy analyzed in single pixels of a CCD image sensor. The results indicate the CCD operates as an array of tiny Si solid state detectors providing both high spatial resolution and x-ray energy discrimination. These devices will prove useful sensors at the focus of future x-ray telescopes.


In vitro assessment of the immunomodulatory effects of multispecies probiotic formulations for management of allergic diseases.
Modulation of the composition of the intestinal microbiota with probiotics could possibly offer a way of prevention or management of allergic diseases. The objective of this study was to determine the immunomodulating effects of various multispecies probiotic combinations in vitro, as preamble to application in vivo. Multispecies probiotic combinations were formulated and tested for their effects on in vitro cytokine production by human mononuclear cells and were compared to products that already have shown beneficial effects in vivo. All 4 tested combinations of probiotics showed a 40-71% decrease of Th2 cytokine production (IL-4, IL-5, and IL-13) and a variable increase of Th1 (IFN-γ) and Treg cytokine (IL-10) production compared to the medium. A specific probiotic mixture that contained Bifidobacterium breve W25, Bifidobacterium lactis ATCC SD 5219, B. lactis ATCC SD 5220, Lactobacillus plantarum W62, Lactobacillus salivarius W57 and Lactococcus lactis W19 was superior in its stimulating effect on IL-10 production (significant better than the other tested combinations; P=0.001). Modulation of in vitro cytokine production profiles can be used to differentiate between selected probiotic formulations for their immunomodulatory properties. In the future it should be demonstrated whether the immunomodulatory capacities from the multispecies probiotic formulation with the desired profile will be effective in vivo (in adolescents, followed by application in children).


Thermally switchable and discretely tunable comb filter with a linearly chirped fiber Bragg grating.
We propose and experimentally demonstrate a novel switchable and discretely tunable comb filter based on a thermally induced linearly chirped fiber Bragg grating. Experimentally we achieved a thermally induced optical bandpass filter that has eight switchable passband peaks with peak separations of 1.6 and 3.2 nm, a very narrow bandwidth (as small as 10 pm) of each peak, a tunable range of 16.5 nm, and a greater than 25 dB rejection ratio. Two spectral peaks separated by only 0.8 nm were also obtained with this comb filter. This filter provides the unique advantages of an all-fiber structure, switchable spectral peaks, independent tuning of the center wavelength and wavelength spacing of the spectral peaks, low polarization sensitivity, simple structure, ease of fabrication, and low cost.


Temporal arteritis: a review and case history.
Temporal cell arteritis is a systemic vasculitis occurring mainly in the elderly. Classic symptoms such as headache, jaw claudication, visual changes, and polymyalgia rheumatica make the diagnosis relatively easy. Occult or asymptomatic presentations, however, are often missed or attributed to another cause. It is important for clinicians to be aware of the diverse presentations of this disease to avoid unnecessary investigations and prevent complications such as visual loss, myocardial ischemia, cerebrovascular accident, and death. This report presents the case of a patient who was referred with anemia and an elevated erythrocyte sedimentation rate, and who developed a headache during the hospital admission.


Complex salt bridges in proteins: statistical analysis of structure and function.
We developed an algorithm to analyze the distribution and geometry of simple and complex salt bridges in 94 proteins selected from the Protein Data Bank. In this study, the term "salt bridging" denotes both non-bonded and hydrogen-bonded paired electrostatic interactions between acidic carboxyl groups and basic amino groups in single or adjacent protein chains. We defined complex salt bridges as those joining more than two charged residues, including Asp, Glu, Lys and Arg, and excluding His. The survey related the following special features of complex salt bridges. (1) The abundance of complex salt bridges is high; one-third of all residues participating in salt-bridge formation were part of complex salt bridges. (2) The geometry of the interaction between acidic and basic residues is very similar in simple and complex salt bridges. Adding one residue to a simple interaction represents a minor change in the geometry but provides the molecule with a more complex interaction, a phenomenon that may explain the cooperative effect of salt bridges in proteins. Such moderate changes in salt-bridge networks can be generated stepwise and reversibly without trapping the protein in a local energetic minimum. (3) One important role of complex salt bridges is connecting protein subunits or joining two secondary structures to form quaternary structures, where they can connect as many as five secondary structure units. (4) Arginine serves as a key connector and/or a branching unit because its geometry allows three possible directions of interactions. The information gained from this study of complex salt bridges should enhance the understanding of protein structure.


The Role of the Skin Barrier in Periorificial Dermatitis.
Periorificial dermatitis, mostly known as perioral dermatitis, is a benign inflammatory facial dermatosis which can be a severe burden and even disfiguring and psychologically disturbing. The disease still presents a challenge for physicians when it comes to etiology and appropriate therapy. Although a variety of extrinsic and intrinsic factors have been proposed as etiopathogenetic factors, none of these fully explain complex pathogenesis of the disease. There is more evidence that supports beliefs that the epidermal barrier dysfunction is an underlying main pathogenic factor that contributes to persistent cutaneous inflammation in typical facial localizations. Patients with periorificial dermatitis are considered hyper-reactors who have impaired essential function of the skin barrier, especially the skin barrier of the perioral region, characterized by thin permeable stratum corneum and imbalance of intercellular lipids, which makes them more susceptible to various internal and external irritants that contribute to the development of the disease. The verification of this connection reinforces the need for clinicians to address this issue when approaching their patients and formulating the best treatment plan. Treatment should emphasize repairing the impaired skin barrier function to minimize associated skin inflammation and sensitivity, which results in resolution of the objective and subjective symptoms.


Wolf-pack buffer zones as prey reservoirs.
In a declining herd, surviving deer inhabited overlapping edges of wolf-pack territories. There, wolves hunted little until desperate, in order to avoid fatal encounters with neighbors. Such encounters reduce wolf numbers and predation pressure and apparently allow surviving deer along territory edges to repopulate the area through dispersal of their prime, less vulnerable offspring into territory cores.


A High Compressibility Pressure-Sensitive Structure Based on CB@PU Yarn Network.
In this work, a piezoresistive sensor structure based on carbon black (CB)@polyurethane (PU) yarn material was developed. Specifically, CB@PU yarn was constructed by the polymer-mediated water-based electrostatic deposition method. The distribution of the yarn was artificially controlled to fabricate conductive networks. The CB conductive layer was efficiently supported by the net-like structure of PU yarn, thus generating collaborative advantage. The as-fabricated pressure sensor not only displayed compressibility of over 97%, but also detected a wide pressure change from 25 Pa to 20 kPa. Furthermore, this sensor exhibited response time of less than 70 ms and reproducibility of over 10,000 cycles. The advantages of the CB@PU network ensured this pressure-sensitive structure enormous potential application in pressure sensitive equipment.


The differential diagnosis and classification of eyelid retraction.
Classification schemes are useful in the formulation of differential diagnoses. Thoughtful commentary has been devoted to the classification of blepharoptosis, but the causes of eyelid retraction have received less attention in published reports. Although eyelid retraction most frequently is associated with Graves ophthalmopathy, numerous other entities may cause the sign. This study was undertaken to provide a more comprehensive differential diagnosis and classification of eyelid retraction. A series of patients with eyelid retraction was studied, and pertinent published reports were reviewed. Forty-four patients with different causes for eyelid retraction are described. Normal thyroid function and regulation were confirmed in all patients in whom Graves ophthalmopathy could not be excluded by clinical, biochemical, or historical criteria. Based on a series of patients and reported cases, a differential diagnosis for eyelid retraction is proposed using a classification system compromising three categories (neurogenic, myogenic, and mechanistic).


Genetics of experimental autoimmune encephalomyelitis in the mouse.
Multiple sclerosis (MS) is an inflammatory, demyelinating disease in the central nervous system (CNS) affecting approximately 0.1% of the population in the northern part of the world. The factors behind the initiation of the inflammatory response are not known at present, but MS is considered as a complex disease depending on genetic as well as environmental factors. Experimental autoimmune encephalomyelitis (EAE) is the prevailing experimental rodent model for multiple sclerosis (MS). Disease is induced in genetically susceptible mice or rats by immunization with myelin proteins or peptides, which leads to an infiltration of leukocytes into the CNS. EAE has been subjected to investigations of genetic susceptibility to disease development. By the identification of genes predisposing to EAE, the hope is to get clues as to what genetic elements are also important in MS. To date, more than 25 Eae loci have been described in the mouse. The quantitative trait loci are linked to different disease traits and several show sex specificity. Here we discuss the current state of the genetics controlling susceptibility to EAE.


Insights into physical activity and cardiovascular disease risk in young children: IDEFICS study.
The association between physical activity and cardiovascular disease risk factors in children has been the focus of research for over two decades. The majority of this research has focused on children over 10 years of age with little information on very young children. The data recently published in BMC Medicine by Jiménez-Pavón and colleagues suggest that adverse cardiovascular disease (CVD) risk profiles, as indicated by a clustered risk score for the metabolic syndrome, are evident in very young children (two to six years of age), but differ between the sexes. The authors evaluated the relationship of CVD risk profiles and protective levels of moderate-to-vigorous physical activity (MVPA) and concluded that boys aged six years or younger needed >60 minutes of MVPA per day, whereas boys from six to nine years of age needed >80 minutes of MVPA per day; girls in either age group needed approximately 15 minutes less. Therefore, when clinicians recommend physical activity for children they should evaluate "at risk" children on a case-by-case basis rather than using generalized guidelines.


[Biotinidase deficiency. Results of neonatal screening 1985-1989 in Lower Saxony].
During a five-year-period (1985-1989) 420,000 newborns in Lower Saxony, FRG, were screened for biotinidase deficiency using biotinyl-para-amino-benzoic-acid as substrate. Three newborns with profound biotinidase deficiency (activity 1.1%, 2.1%, 2.3% of mean normal activity level) were detected. Nine newborns had partial biotinidase deficiency (activity 17-26% of mean normal activity level), thus giving an incidence of 1:140,000 with profound, and 1:46,667 with partial biotinidase deficiency, respectively. The infants with profound biotinidase deficiency are treated with biotin (2 x 5 mg/day) from the 3rd, 6th and 8th week of life and have developed normally so far. The children with partial biotinidase deficiency are not treated but followed up closely. The necessity of newborn screening for biotinidase deficiency is stressed.


Role of tamoxifen in the induction of hormone-independent rat mammary tumors.
Using the dimethylbenzanthracene-induced rat mammary tumor model, we examined the appearance and growth of tumors in animals given tamoxifen (TAM) either coincident with dimethylbenzanthracene or after initial tumor formation. While fewer tumors arose after coadministration of antiestrogen and carcinogen and TAM treatment caused regression of most existing tumors, new tumors developed in the presence of TAM in both studies. Since none of these new tumors regressed following ovariectomy, all were classified as hormone independent. Furthermore, these independent tumors grew more rapidly than both control-dependent and independent tumors, resulting in a greater average volume. These data suggest that a more aggressive form of hormone-independent tumor appears during TAM treatment.


Inhibitory amino acid transmitters associated with axons in presynaptic apposition to cutaneous primary afferent axons in the cat spinal cord.
The purpose of the present study was to characterize the transmitter content of structures in presynaptic apposition to the central terminals of cutaneous afferent fibers in the dorsal horn of the spinal cord. Axons in the Aalphabeta conduction velocity range were identified in adult cats, stained intra-axonally with horseradish peroxidase, and prepared for combined light and electron microscopy. In total, we labeled two slowly adapting (Type 1) axons, two hair-follicle afferents, and one rapidly adapting (Krause) afferent. Ninety-nine labeled boutons were examined through complete series of serial sections. Approximately 80% of boutons originating from rapidly adapting and hair-follicle afferents were postsynaptic to other axons, but only 50% of boutons from slowly adapting axons were associated with this type of arrangement. Postembedding immunogold reactions revealed that between 80% (for slowly adapting axons) and 100% (for rapidly adapting axons) of boutons presynaptic to primary afferents were immunoreactive for gamma-aminobutyric acid (GABA). The vast majority of these terminals (in excess of 80%) were also enriched with glycine. Therefore, presynaptic inhibition of these three functional classes of Aalphabeta cutaneous primary afferents is mediated principally by the subgroup of GABAergic interneuron that also contains glycine.


Possible case of spondylo-epiphyseal dysplasia in a medieval skeleton.
Multiple anomalies of vertebral and long bone growth were observed in the incomplete skeleton of an adult male from a collection of 693 medieval skeletons excavated at Abingdon, Oxfordshire. The skeleton consists of a fragmented skull, right scapula and humerus, left humerus, radius, ulna and partial hand, vertebrae from C1 to T11, and fragments of the ribs and sternum. The bones were examined, measured, and radiographed. The humeri are abnormally short and thick, with exaggerated muscle attachments. Both shoulder joints show extensive osteoarthritic destruction. Some vertebrae show slight flattening of the bodies, and there is possible evidence of both kyphosis and scoliosis. Skull, forearm, and hand bones are of normal size and morphology. Lack of lower limb bones and abnormal proportions in the upper limbs prevent meaningful estimation of stature. However, the other features of the skeleton are consistent with a diagnosis of spondylo-epiphyseal dysplasia. No other skeletons displaying similar anomalies were observed.


Potassium transport in corn roots : I. Resolution of kinetics into a saturable and linear component.
Influx isotherms were obtained for (86)Rb(+) uptake into 2-cm corn (Zea mays [A632 x (C3640 x Oh43)] root segments for both low- (0.2 millimolar CaSO(4)) and high-salt (0.2 millimolar CaSO(4) + 5 millimolar KCl) grown roots. Unlike the discontinuous curves usually presented for K(+) influx, our isotherms were smooth, nonsaturating curves that approached linearity at K(+) (Rb(+)) concentrations above 1 millimolar. The kinetics for K(+) transport could be resolved into saturable and linear components. The saturable components yielded K(m) values of 16 and 86 micromolar for low- and high-salt roots, respectively, while V(max) values were 5.62 and 1.85 moles per gram fresh weight per hour. Results of experiments with the penetrating sulfhydryl reagent, N-ethyl maleimide (NEM), and the impermeant reagent, p-chloromercuribenzene sulfonic acid (PCMBS) indicated that the saturable and linear components were independent mechanisms of K(+) transport.Short-term NEM exposures (30 seconds to 5 minutes) selectively inhibited the saturable system, but had little effect on the linear component. Increasing NEM exposures resulted in further inhibition and subsequent abolition of the saturable component; the linear component exhibited limited NEM sensitivity. PCMBS elicited the same general inhibitory trends, although it was less effective as a saturable component inhibitor.The effects of NEM and PCMBS on K(+) efflux were also studied. Short NEM exposures had no effect on cytoplasmic efflux, while inhibiting vacuolar efflux significantly. From these data, it is unclear at which site(s) NEM is acting. A more complex response was obtained with PCMBS, where a monophasic efflux curve was observed. Analysis indicated that the vacuolar efflux was stimulated, while the cytoplasmic component was abolished.The nature of the linear component is discussed, and it is proposed that the mechanism may be more complex than simple facilitated diffusion.


Effect of carnitine supplement to the dam on plasma carnitine concentration in the sucking foal.
The changes in carnitine in plasma and milk during the first 3 months of lactation were studied in 14 broodmares and their foals. Six of the mares (Group S) were given a supplement of 10 g carnitine split between the morning and evening feeds, starting 2 weeks before birth. At birth the plasma carnitine concentration in Group S mares was about twice that in Group NS mares (no supplement). In both groups the concentration initially declined in the days after birth. Whilst this trend was reversed in Group S mares, the concentration in Group NS mares remained at a reduced level for the remainder of the study. Milk concentrations declined continuously over the monitoring period in both groups. There was no apparent relationship between milk and plasma concentrations. Despite this the milk concentration tended to be higher in Group S than in Group NS mares although differences were not significant. There was an immediate drop in the plasma concentration in foals after birth which was reversed in foals of Group S mares but not in those of Group NS mares. There were no apparent side effects of carnitine supplementation.


Optimization of Photopolymer Materials for the Fabrication of a Holographic Waveguide.
In this work, we present a method of manufacturing an optical see-through display based on a holographic waveguide with transmission holograms that couple the incident light between air and the glass substrate, accomplishing total internal reflection. The holograms (slanted transmission gratings with a spatial frequency of 1700 lines/mm) were recorded on a polyvinyl alcohol acrylamide (PVA/AA) photopolymer. We will also show that the addition of N,N'-methylene-bis-acrylamide (BMA) to the composition of the photopolymer allows the achievement of the index modulations necessary to obtain high diffraction efficiencies in non-slanted diffraction gratings of 1000 and 2200 lines/mm, and also in slanted gratings of 1700 lines/mm (which are the base of the optical system proposed).


Visual neglect: does it exist in children with unilateral brain lesion? A systematic review.
Visual Neglect (VN) is a common neuropsychological disorder in adults with unilateral brain lesion (UBL), characterized by the failure to attend and to report sensory events occurring in one side of space, contralateral to an area of brain damage. Less is known about VN expression in children following brain injury. The aim of this systematic review is to evaluate the presence of VN in UBL children and to identify the best neuropsychological assessment's tool for this population. A comprehensive search of 4 databases (Pubmed, Cochrane Database, SCOPUS, DARE) was undertaken from May 2020 to January 2021. Inclusion criteria were (i) subjects less than 18 years with cerebral lesions and with MRI, (ii) specific neuropsychological assessments for VN, (iii) studies published in English since 2000. A total of 309 articles were found in the initial search but only 10 observational studies met the full inclusion criteria. In these studies, 1051 subjects were evaluated for VN, of them 749 were controls and 302 had brain lesions. The two most common types of neuropsychological tools used in children with unilateral brain damage to assess the presence of VN were target cancellation tests and drawing tests.This review confirms the possibility that children with UBL can develop VN, even if it is not very clear which brain structure's characteristics can increase this risk. Children with right lesion showed visuo-spatial attention deficits focalized on the contralateral side, compatible with diagnosis of VN, while children with left lesion showed more generalized attention difficulties. The overall level of evidence correlating the presence of VN and different types of UBL in children was low and neuropsychological assessment of VN for children are sparse. Some important limitations of this review must be reported: the limited number of studies included, the administration of various types of tests to evaluate VN, the lack of information regarding the cognitive level of children in most of the studies. Further research is needed to understand patterns of VN based on brain structure and time since lesion.Systematic Review Registration: ID on PROSPERO: CRD42021281993.


The role of the parent-child relationship in fostering resilience in American Indian/Alaskan Native children.
Resilience is a key characteristic to study in families, particularly those who have experienced significant systemic risk factors. While much resilience research focuses on ethnic and cultural minorities, little research focuses specifically on American Indian/Alaskan Native (AI/AN) families. The parent-child relationship has been demonstrated to be a key characteristic in families, and this relationship may also serve as a protective factor for AI/AN families. Positive parent-child relationships are consistently linked to positive child outcomes, and parental psychological symptoms are linked with child psychological symptoms in non-Native families. These associations warrant further examination among AI/AN families. We hypothesized that the parent-child relationship would moderate the link between parent distress (i.e., depressive and anxious symptoms) and child internalizing problems in a sample of 57 AI/AN parents of children 3-5 years of age. As expected, the parent-child relationship moderated the associations between parent anxiety symptoms and child internalizing symptoms, and between parent depressive symptoms and child internalizing symptoms. Furthermore, the strength of the parent-child relationship buffered the effects of parent distress on child internalizing symptoms. Results highlight the potentially protective role of strong parent-child relationships in AI/AN families.


Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives.
Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihypertensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experimental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacological mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na+,K+ and Ca2+ ion currents. Differing from quinidine and sotalol, which exhibited reverse use-dependent effect, dauricine prolonged APD in a normal use-dependent manner in experimental studies. The antiarrhythmic effect of daurisoline and neferine which is an alkaloid isolated from Nelumbo nucifera Gaertn, and their mechanisms of actions have also been studied. The antiarrhythmic effect of daurisoline is more potent than that of dauricine.


Enzymatic basis for hydrolytic versus phosphorolytic mRNA degradation in Escherichia coli and Bacillus subtilis.
The rapid synthesis and breakdown of mRNA in prokaryotes can impose a significant energy drain on these cells. Previous in vivo studies [Duffy, J. J., Chaney, S. G. & Boyer, P. D. (1972) J. Mol. Biol. 64, 565-579; Chaney, S. G. & Boyer, P. D. (1972) J. Mol. Biol. 64, 581-591] indicated that while RNA turnover in Escherichia coli was hydrolytic, it was nonhydrolytic in Bacillus subtilis. Here we provide an explanation for these observations based on enzymatic analysis of extracts of these two organisms. RNA degradation to the mononucleotide level in E. coli extracts is due solely to two active ribonucleases, RNase II and polynucleotide phosphorylase, which act hydrolytically and phosphorolytically, respectively. RNase II activity represents close to 90% of the total activity of the extract, as expected for predominantly hydrolytic degradation in this organism. In contrast, RNase II is absent from B. subtilis extracts, and the primary mode of RNA degradation is phosphorolytic, employing the Bacillus equivalent of polynucleotide phosphorylase and releases nucleoside diphosphates as products. A low level of a Mn2(+)-stimulated, hydrolytic ribonuclease is also detectable in B. subtilis extracts. Overall, E. coli and B. subtilis extracts differ by about 20- to 100-fold, depending on the substrate, in their relative use of hydrolytic and phosphorolytic routes of RNA degradation. The relation of the mode of mRNA degradation to the environment of the cell is discussed.


The virtual hospital. Providing multimedia decision support tools via the Internet.
Physicians in the clinical setting remain isolated from important sources of medical information. The authors have created a multimedia database known as The Virtual Hospital that improves access to current medical data, which is used to improve patient care decisions. The Virtual Hospital is a digital health sciences library stored on a server (computer) at The University of Iowa and delivered via the Internet to inexpensive personal computers in the workplace. The emerging standard of the World Wide Web is used to provide cross-platform distribution.


Value of duplex and color doppler ultrasonography in the evaluation of orbital vascular flow and resistance in sickle cell disease.
The aim of the present study was to assess and to compare the orbital and retinal vascular flow dynamics and resistance in patients with homozygous sickle cell disease with controls by means of duplex and color Doppler ultrasonography. Forty-six patients with homozygous sickle cell disease (SCD) and 20 healthy subjects were included in the study. None of the patients had objective signs of ocular involvement. Duplex and color Doppler ultrasonography of the ophthalmic, short posterior ciliary, and central retinal arterial flows of the both eyes were performed to assess peak systolic flow velocity (PSFV), end-diastolic flow velocity (EDFV), and mean flow velocity (MFV) through entire cardiac cycle with further calculation of resistive indices (RI) and pulsatility indices (PI). Ophthalmic arterial flow velocities were significantly increased in patients with SCD than in controls (P < 0.0001). Blood flow velocities of the central retinal artery were found to be significantly reduced (P < 0.0001) while RI and PI values were markedly higher (P < 0.02 and P < 0.03) in patients with SCD compared to controls. Reduction of retinal vascular flow velocities and increase of retinal vascular resistance were significantly related to the mean hemoglobin and hematocrit levels, red blood cell count, and mean corpuscular hemoglobin volume (P < 0.009, P < 0.01, P < 0.02, and P < 0.04, respectively). In conclusion, Doppler ultrasonography in patients with SCD who had no objective signs of ocular involvement allowed detection enhancement of ophthalmic flow velocities, reduced retinal flow velocities, and increased retinal vascular resistance, which are associated with haematological features.


A Longitudinal Study of the Predictors of Perceived Procedural Justice in Australian University Staff.
This study examined the factors that predict employees' perceptions of procedural justice in university settings. The paper also reviews the ethical aspects of justice and psychological contracts within employment relationships. The study examined the predictors of perceived procedural justice in a two-wave longitudinal sample of 945 employees from 13 universities by applying the Job Demands-Resources theoretical model of stress. The proposed predictors were classified into two categories: Job demands of work pressure and work-home conflict; and job resources of job security, autonomy, trust in senior management, and trust in supervisor. The predictor model also examined job satisfaction and affective organizational commitment, demographic (age, gender, tenure, role) and individual characteristics (negative affectivity, job involvement) as well as Time 1 (T1) perceptions of procedural justice to ensure that tests were rigorous. A series of hierarchical multiple regression analyses found that job satisfaction at T1 was the strongest predictor of perceived procedural justice at Time 2. Employees' trust in senior management, and their length of tenure also positively predicted justice perceptions. There were also differences between academic and non-academic staff groups, as non-academic employees' level of job satisfaction, trust in senior management, and their length of organizational tenure predicted procedural justice perceptions, whereas for academics, only job satisfaction predicted perceived justice. For the "all staff" category, job satisfaction was a dominant and enduring predictor of justice, and employees' trust in senior management also predicted justice. Results highlight the importance of workplace factors in enhancing fair procedures to encourage reciprocity from employees. As perceived procedural justice is also conceptually linked to the psychological contract between employees-employers, it is possible that employees' levels of job satisfaction and perceptions of trust in senior management, relative to other work attitudinal outcomes, may be more effective for improving the broader working environment, and promoting staff morale. This study adds to research on applied business ethics as it focuses on the ethical aspects of perceived procedural justice and highlights the importance of workplace factors in enhancing fair procedures in organizational policy to encourage reciprocity and promote healthy organizational environments.


Nonimmune phagocytosis of liposomes by rat alveolar macrophages is enhanced by vitronectin and is vitronectin-receptor mediated.
Pulmonary alveolar macrophages (AMs) engulf diverse materials. The mechanisms allowing AMs to recognize, bind, and phagocytose these materials are poorly understood. To test the hypothesis that the adhesive glycoprotein vitronectin (Vn) acts as a nonimmune opsonin, we studied AM-Vn binding and AM phagocytosis of fluorescent liposomes under the following conditions: (1) pretreatment of AMs with Vn, followed by incubation of AMs with liposomes containing increased amounts of Vn; (2) inhibition of phagocytosis by gly-arg-gly-asp-ser (RGD) and gly-pen-gly-arg-gly-asp-ser-pro-cys-ala (GPen); and (3) antibody blockade of the alpha(v)beta3 vitronectin receptor (VnR). Pretreatment of AMs with 0.1, 1, and 2 microM Vn progressively enhanced AM-Vn binding from 23,622 +/- 3,328 cpm to 40,847 +/- 6,530 cpm, 57,149 +/- 2,789 cpm, and 124,852 +/- 42,930 cpm, respectively (P < 0.05). AM pretreatment also increased phagocytosis of Vn-enriched liposomes, but not empty liposomes (20.7 +/- 0.4 liposomes/cell versus 11.5 +/- 0.5 liposomes/cell, P < 0.05). Moreover, increased concentrations of Vn in liposomes progressively increased phagocytic activity (3.7 +/- 0.3, 6.5 +/- 0.2, 11.5 +/- 0.5, and 16.5 +/- 0.6 liposomes/cell with 0.01, 0.1, and 1 microM Vn, respectively, P < 0.05). RGD inhibited Vn-enhanced phagocytosis (8.1 +/- 0.4 liposomes/cell to 3.4 +/- 0.2, 2.4 +/- 0.4, and 2.2 +/- 0.2 liposomes/cell with 0.02, 0.2, and 2 mM RGD, respectively, P < 0.05), as did GPen (4.7 +/- 0.8 liposomes/cell versus control = 10.9 +/- 1.5 liposomes/cell, P < 0.05) and anti-VnR antibody (3.3 +/- 0.4 liposomes/cell versus control = 8.9 +/- 1.7 liposomes/cell, P < 0.05). We conclude that AMs employ Vn as a nonimmune opsonin to enhance the efficiency of phagocytosis.


RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer.
The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncovering potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mammalian target of rapamycin (PI3K/mTOR) blockade, including the ribosomal S6 kinases RPS6KA2 (RSK3) and RPS6KA6 (RSK4). We demonstrate that overexpression of RSK3 or RSK4 supports proliferation upon PI3K inhibition both in vitro and in vivo, in part through the attenuation of the apoptotic response and upregulation of protein translation. Notably, the addition of MEK- or RSK-specific inhibitors can overcome these resistance phenotypes, both in breast cancer cell lines and patient-derived xenograft models with elevated levels of RSK activity. These observations provide a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable responses in breast cancer patients with activated RSK.


Ribonuclease H from K562 human erythroleukemia cells. Purification, characterization, and substrate specificity.
The major ribonuclease H from K562 human erythroleukemia cells has been purified more than 4,000-fold. This RNase H, now termed RNase H1, is an endoribonuclease whose products contain 5'-phosphoryl and 3'-hydroxyl termini. The enzyme has a native molecular weight of 89,000 based on its sedimentation and diffusion coefficients. Human RNase H1 has an absolute requirement for a divalent cation. Maximal activity is obtained with either 10 mM Mg2+, 5 mM Co2+, or 0.5 mM Mn2+. The pH optimum is between 8.0 and 8.5 in the presence of 10 mM Mg2+. The isoelectric point is 6.4. RNase H1 lacks double-stranded and single-stranded RNase and DNase activities, and it will not hydrolyze the DNA moiety of an RNA.DNA heteroduplex. Unlike the Escherichia coli enzyme, which requires a heteroduplex that contains at least four consecutive ribonucleotides for activity, human RNase H1 can hydrolyze a DNA.RNA.DNA/DNA heteroduplex that contains a single ribonucleotide. Cleavage occurs at the 5' phosphodiester of this residue. This substrate specificity suggests that human RNase H1 could play a role in ribonucleotide excision from genomic DNA during replication.


Anti-allergic activity of standardized extract of Albizia lebbeck with reference to catechin as a phytomarker.
The major groups of phytonutrients found in plants include polyphenols, flavonoids, terpenes, amines, etc., all of which are observed to have potential anti-allergic activity. In this study, we evaluated the anti-allergic activity of the standardized extract of Albizia lebbeck with respect to the catechin, a polyphenolic phytomarker. The percentage of catechin in the ethanolic extract was found to be 14.72 mg/g. We administered Albizia lebbeck (50-300 mg/kg) and 50 mg/kg of catechin to mice to evaluate the mast cell stabilization and estimation of histamine elevation in the plasma. Results support the conclusion that Albizia lebbeck at different concentrations has got potent mast cell stabilizing property and the IC(50) value of Albizia lebbeck was found to be 85 microg/ml. This inhibitory potential of catechin from Albizia lebbeck is perhaps due to modulation of two important effector's functions, histamine release and cytokine expression of antigen -IgE activated mast cells.


Rapid identification of the primary motor area by using magnetic resonance axonography.
To identify the primary motor area (PMA) quickly and correctly, the authors used magnetic resonance (MR) axonography, including anisotropic diffusion-weighted (DW) MR imaging and three-dimensional anisotropic contrast (3DAC) imaging, which was performed to visualize the corticospinal tract mainly originating from the PMA. All studies were obtained in 10 normal volunteers and in 17 patients with brain tumors affecting the central motor system. Data sets of anisotropic DW imaging and anatomical and functional (f)MR imaging were acquired while the participants executed simple hand movements. Offline processing of 3DAC MR axonography images was subsequently done to extract only the anisotropic components of the tract fibers. Somatosensory evoked fields (SSEFs) and intraoperative cortical somatosensory evoked potentials (SSEPs) were recorded after electrical stimulation of the median nerve. In normal volunteers, anisotropic DW imaging, 3DAC imaging, fMR imaging, and magnetoencephalography consistently localized the PMA in both hemispheres. In contrast, fMR imaging and SSEFs failed to identify the PMA in seven and one of the 17 patients, respectively, because of cortical dysfunctions due to brain tumor. The anisotropic DW imaging data acquired within 30 seconds with no patient tasks successfully identified the PMA in 12 patients, and failed in five patients because of the lesions involving the frontal lobe. The anisotropic axonal components were distinctly visualized on 3DAC images and indicated the PMA location, which was confirmed on intraoperative SSEPs in all 17 affected hemispheres. Swift and noninvasive PMA identification by rapid scanning with MR axonography is a promising method for routine clinical use and is especially beneficial for patients who have severe cortical dysfunction in the PMA.


The Origin of Vertebrate Gills.
Pharyngeal gills are a fundamental feature of the vertebrate body plan [1]. However, the evolutionary history of vertebrate gills has been the subject of a long-standing controversy [2-8]. It is thought that gills evolved independently in cyclostomes (jawless vertebrates-lampreys and hagfish) and gnathostomes (jawed vertebrates-cartilaginous and bony fishes), based on their distinct embryonic origins: the gills of cyclostomes derive from endoderm [9-12], while gnathostome gills were classically thought to derive from ectoderm [10, 13]. Here, we demonstrate by cell lineage tracing that the gills of a cartilaginous fish, the little skate (Leucoraja erinacea), are in fact endodermally derived. This finding supports the homology of gills in cyclostomes and gnathostomes, and a single origin of pharyngeal gills prior to the divergence of these two ancient vertebrate lineages.


A Structural Equation Model of the relationship between physical activity and quality of life.
Background/Objective: Literature shows that practicing physical activity improves the general health and quality of life of people with intellectual disabilities. However, there is little empirical research on the specific benefits physical activity provides and to what extent these benefits occur. The goal of this study was to examine the impact of perceptions of physical activity and the individualized support on each of eight quality of life-related domains and three higher-order quality of life factors. Method: The sample consisted of adults with intellectual disability (n = 529), their assigned professionals (n = 522), and a family member (n = 462). Most participants attended day and residential services, and we applied the Personal Outcomes Scale and the Support Needs and Strategies for Physical Activity Scale to all of them. Results: The structural model parameter estimation showed high values, especially for the factor of well-being. These data allowed us to confirm that perceptions of physical and individualized supports in the field of physical activity act as predictors of quality of life improvement. Conclusions: The results suggest that organizations devoted to enhancing personal outcomes should include physical activity in their programs, and revise both their own services and the use of physical activity resources available in the community.


Overall survival and updated results from a phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma.
In a phase II, open-label, multicentre Japanese study, sunitinib demonstrated antitumour activity and acceptable tolerability in metastatic renal cell carcinoma patients. Final survival analyses and updated results are reported. Fifty-one Japanese patients with a clear-cell component of metastatic renal cell carcinoma (25 treatment-naïve; 26 cytokine-refractory) received sunitinib 50 mg orally, once daily (Schedule 4/2). Overall and progression-free survivals were estimated by the Kaplan-Meier method. Objective response rate (per Response Evaluation Criteria in Solid Tumours) and safety were assessed with an updated follow-up. First-line and pretreated patients received a median 6.0 and 9.5 treatment cycles, respectively. Investigator-assessed, end-of-study objective response rate was 52.0, 53.8 and 52.9% in first-line, pretreated and overall intent-to-treat populations, respectively. The median progression-free survival was 12.2 and 10.6 months in first-line and pretreated patients, respectively. Fourteen patients per group died (56 and 54%), and the median overall survival was 33.1 and 32.5 months, respectively. The most common treatment-related Grade 3 or 4 adverse events and laboratory abnormalities were fatigue (24%), hand-foot syndrome (18%), decreased platelet count (55%), decreased neutrophil count (53%) and increased lipase (49%). No Grade 5 treatment-related adverse events occurred. Forty patients (78%) required dose reduction, and 13 (25%) discontinued, due to treatment-related adverse events. With the median overall survival benefit exceeding 2.5 years, and acceptable tolerability, in first-line and pretreated Japanese metastatic renal cell carcinoma patients with Eastern Cooperative Oncology Group performance status 0/1, sunitinib showed a favourable risk/benefit profile, similar to Western studies. However, there was a trend towards greater efficacy and more haematological adverse events in Japanese patients.


Three sequential outbreaks of Group A Streptococcus over a two-year period at the Canadian Forces Leadership and Recruit School, St. Jean Garrison, Québec.
Since December 2016, the basic military training (BMT) facility for the Canadian Armed Forces (CAF) has experienced repeated outbreaks of Group A Streptococcus (GAS). In 2018, a voluntary mass antibiotic prophylaxis (MAP) program was implemented to interrupt GAS transmission among recruits. The objective of this study was to describe the epidemiology of three GAS outbreaks and a period of increased pharyngitis infections at the CAF BMT facility in Québec over a two-year span, and to detail the prevention and control measures implemented to mitigate the risk to recruit health. Descriptive data were collected on invasive and severe GAS cases along with laboratory data including genotyping of throat swabs from recruits presenting with pharyngitis. A laboratory-based acute respiratory infection surveillance system was used to aid in monitoring and decision-making. Close contacts of recruits were assessed for asymptomatic GAS carriage and MAP adverse events surveillance was conducted. Three distinct GAS outbreaks occurred at the Canadian Forces Leadership and Recruit School totaling eight invasive (iGAS) and 13 severe (sGAS) cases over two years. All iGAS/sGAS cases, apart from one instructor, were among recruits. The predominant strain in all three outbreaks was type emm6.4. A total of 11,293 recruits received MAP (penicillin G benzathine or azithromycin) between March 7, 2018 and November 18, 2019. There were eight reported serious adverse events related to penicillin administration. The CAF BMT facility experienced three GAS outbreaks over the course of two years, and despite the use of enhanced hygiene measures, only MAP has been effective in quelling these outbreaks.


Application of A Mobile Platform-based System for the Management of Fundus Diease in Outpatient Settings.
Objective To evaluate the application of a mobile platform-based system in the management of fundus disease in outpatient settings. Methods In the outpatient departments of fundus disease,premature babies requiring eye examination under general anesthesia and adults requiring intraocular surgery were enrolled as the subjects. According to the existing clinical practices,we developed a system that met the requirements of clinical practices and optimized the clinical management. Based on the FileMaker database,the tablet computers were used as the mobile platform and the system could also be run in iPad and PC terminals.Results Since 2013,the system recorded 7500 cases of special examinations. Since July 2015,4100 cases of intravitreal drug injection were also recored in the system. Multiple-point and real-time reservation pattern increased the efficiency and opimize the clinical management. All the clinical data were digitalized. Conclusion The mobile platform-based system can increase the efficacy of examination and other clinical processes and standardize data collection;thus,it is feasible for the clinical practices in outpatient departments of ophthalmology.


Inhibitory region of troponin I: Ca(2+)-dependent structural and environmental changes in the troponin-tropomyosin complex and in reconstituted thin filaments.
In muscle thin filaments, the inhibitory region (residues 96-117) of troponin I (TnI) is thought to interact with troponin C (TnC) in the presence of Ca(2+) and with actin in the absence of Ca(2+). To better understand these interactions, we prepared mutant TnIs which contained a single Cys-96 or Cys-117 and labeled them with the thiol-specific fluorescent probe N-(iodoacetyl)-N'-(1-sulfo-5-naphthyl)ethylenediamine (IAEDANS). We characterized the microenvironments of the AEDANS labels on TnI in the presence and absence of Ca(2+) by measuring the extent of acrylamide quenching of fluorescence and lifetime-resolved anisotropy. In the troponin-tropomyosin (Tn-Tm) complex, the AEDANS labels on both Cys-96 and Cys-117 were less accessible to solvent and less flexible in the presence of Ca(2+), reflecting closer interactions with TnC under these conditions. In reconstituted thin filaments, the environment of the AEDANS on Cys-96 was not greatly affected by Ca(2+), while the AEDANS on Cys-117 was more accessible but significantly less flexible as it moved away from actin and interacted strongly with TnC in the presence of Ca(2+). We used fluorescence resonance energy transfer (FRET) to measure distances between AEDANS on TnI Cys-96 or Cys-117 and 4-¿[(dimethylamino)phenyl]azo¿phenyl-4'-maleimide (DABmal) on actin Cys-374 in reconstituted thin filaments. In the absence of Ca(2+), the mean distances were 40.2 A for Cys-96 and 35.2 A for Cys-117. In the presence of Ca(2+), Cys-96 moved away from actin Cys-374 by approximately 3.6 A, while Cys-117 moved away by approximately 8 A. This suggests the existence of a flexible "hinge" region near the middle of TnI, allowing amino acid residues in the N-terminal half of TnI to interact with TnC in a Ca(2+)-independent manner, while the C-terminal half of TnI binds to actin in the absence of Ca(2+) or to TnC in the presence of Ca(2+). This is the first report to demonstrate structural movement of the inhibitory region of TnI in the thin filament.


Phlegmonous duodenitis complicating multiple myeloma: a successfully treated case.
A patient receiving chemotherapy for multiple myeloma suddenly developed an acute abdomen, fever, and neutrophil leukocytosis. At laparotomy, the distal two-thirds of the duodenum was swollen and hemorrhagic and was surgically excised. The specimen displayed an acute phlegmonous (suppurative) duodenitis with submucosal and transmural acute inflammation and edema despite an intact mucosa. Blood cultures grew Group B, beta-hemolytic streptococci and gram-positive cocci were present histologically. The patient recovered uneventfully following the surgery and a course of broad spectrum antibiotic therapy. This case illustrates that localized suppurative intestinal infection should be considered when immunosuppressed patients present with an acute abdomen, and that aggressive surgical and antibiotic therapy is warranted.


The importance of accessory protein variants in the pathogenicity of SARS-CoV-2.
The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2) with an estimated fatality rate of less than 1%. The SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 possess putative functions to manipulate host immune mechanisms. These involve interferons, which appear as a consensus function, immune signaling receptor NLRP3 (NLR family pyrin domain-containing 3) inflammasome, and inflammatory cytokines such as interleukin 1β (IL-1β) and are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins were observed across six continents of all complete SARS-CoV-2 proteomes based on the data reported before November 2020. A decreasing order of percentage of unique variations in the accessory proteins was determined as ORF3a > ORF8 > ORF7a > ORF6 > ORF10 > ORF7b across all continents. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. These findings suggest that the wide variations in accessory proteins seem to affect the pathogenicity of SARS-CoV-2.


NMR structure and dynamics of the Specifier Loop domain from the Bacillus subtilis tyrS T box leader RNA.
Gram-positive bacteria utilize a tRNA-responsive transcription antitermination mechanism, designated the T box system, to regulate expression of many amino acid biosynthetic and aminoacyl-tRNA synthetase genes. The RNA transcripts of genes controlled by this mechanism contain 5' untranslated regions, or leader RNAs, that specifically bind cognate tRNA molecules through pairing of nucleotides in the tRNA anticodon loop with nucleotides in the Specifier Loop domain of the leader RNA. We have determined the solution structure of the Specifier Loop domain of the tyrS leader RNA from Bacillus subtilis. Fifty percent of the nucleotides in the Specifier Loop domain adopt a loop E motif. The Specifier Sequence nucleotides, which pair with the tRNA anticodon, stack with their Watson-Crick edges rotated toward the minor groove and exhibit only modest flexibility. We also show that a Specifier Loop domain mutation that impairs the function of the B. subtilis glyQS T box RNA disrupts the tyrS loop E motif. Our results suggest a mechanism for tRNA-Specifier Loop binding in which the phosphate backbone kink created by the loop E motif causes the Specifier Sequence bases to rotate toward the minor groove, which increases accessibility for pairing with bases in the anticodon loop of tRNA.


BET 2: Is virtual reality effective in reducing adult pain perception during medical procedures?
A short-cut review of the available medical literature was carried out to establish whether virtual reality was an effective method for pain control during medical procedures. After abstract review, fifteen papers were found to answer this clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that there is insufficient high-quality research to answer this question.


Light-modulation of gel stiffness: a glyconucleoside based bolaamphiphile as a photo-cleavable low molecular weight gelator.
Photo-cleavable glyconucleoside bolaamphiphiles containing a nitrophenyl unit feature gelation abilities in aqueous media. The stiffness of the resulting gels can be modulated upon light irradiation thanks to the photocleavage reaction of nitrophenyl moieties.


Neuroprotective effect of Bax-inhibiting peptide on neonatal brain injury.
Mitochondria play a critical role in mediating cell death in both the adult and immature brain. The cyclophilin D mitochondrial membrane permeability transition pore is critical in adult ischemia, whereas in neonatal hypoxic-ischemic (HI) brain injury, mitochondrial permeabilization appears to be primarily Bax-dependent. The aim of this study was to evaluate the neuroprotective effect of a cell-penetrating Bax-inhibiting peptide (BIP) on neonatal mouse HI brain injury. BIP (5 microL, 5 mg/mL) or a BIP-negative control (5 microL, 5 mg/mL) was injected intracerebroventricularly immediately before HI in postnatal day 9 mice. Mice were euthanized at different time points after HI for evaluation of brain injury, Bax activation, release of proapoptotic proteins, and caspase activation. The trace fear conditioning and cylinder tests were performed for evaluation of the functional recovery after BIP treatment. At 5 days after HI, there was a 41.2% reduction of brain injury in BIP-treated mice compared with BIP-negative control treated animals. Myelin basic protein and neurofilament quantification revealed that BIP reduced white matter injury. BIP treatment conferred improvement in both sensorimotor and memory functions at 7 weeks after HI. BIP protection was associated with a reduction of Bax activation, mitochondrial permeabilization, and downstream caspase activation. Bax inhibition provides neuroprotection and functional improvement in a neonatal mouse model of HI.


Biological Planning of Radiation Dose Based on In Vivo Dosimetry for Postoperative Vaginal-Cuff HDR Interventional Radiotherapy (Brachytherapy).
(1) Background: Postoperative vaginal-cuff HDR interventional radiotherapy (brachytherapy) is a standard treatment in early-stage endometrial cancer. This study reports the effect of in vivo dosimetry-based biological planning for two different fractionation schedules on the treatment-related toxicities. (2) Methods: 121 patients were treated. Group A (82) received 21 Gy in three fractions. Group B (39) received 20 Gy in four fractions. The dose was prescribed at a 5 mm depth or to the applicator surface according to the distance between the applicator and the rectum. In vivo dosimetry measured the dose of the rectum and/or urinary bladder. With a high measured dose, the dose prescription was changed from a 5 mm depth to the applicator surface. (3) Results: The median age was 66 years with 58.8 months mean follow-up. The dose prescription was changed in 20.7% of group A and in 41% of group B. Most toxicities were grade 1-2. Acute urinary toxicities were significantly higher in group A. The rates of acute and late urinary toxicities were significantly higher with a mean bladder dose/fraction of >2.5 Gy and a total bladder dose of >7.5 Gy. One patient had a vaginal recurrence. (4) Conclusions: Both schedules have excellent local control and acceptable rates of toxicities. Using in vivo dosimetry-based biological planning yielded an acceptable dose to the bladder and rectum.


Genome-wide analysis of changes in early gene expression induced by oestrogen.
The sex hormone 17beta-oestradiol (E2) has profound effects on many aspects of reproduction, development, as well as behaviour. Although the oestrogen receptor is well characterized on a molecular level, relatively few genes affected by E2 have been identified, and the mechanisms underlying the physiological changes caused by E2 are largely unknown. In order to identify oestrogen-regulated genes in vivo, early uterine gene expression profiles were developed using DNA microarrays. Ovariectomized mice were exposed to 17beta-oestradiol for 6 h, and mRNA expression analysis for 9977 genes was performed. Although a large number of genes was affected by oestrogen administration, the genes that showed higher reproducibility in repetitive experiments were selected and further examined. For most of the selected genes, expression was induced in a dose-dependent manner, and gene expression was not altered following oestrogen treatment in oestrogen receptor-alpha (ER(alpha))-deficient mice. In combination with the estimation of gene expression levels using quantitative PCR, it was revealed that multiple genes related to sterol biosynthesis, tRNA synthesis, RNA processing, and growth signalling were activated. Based on the microarray data, we selected additional genes related to sterol biosynthesis and tRNA synthesis and confirmed that these genes are also activated by oestrogen. Genes suggesting a basis for the drastic uterotrophic effect observed several days following oestrogen administration were identified. These findings not only reveal the diverse effect of oestrogen signalling on transcript levels in vivo but also demonstrate the ability of DNA microarrays to identify cellular pathways affected by oestrogen.


Dopamine receptors reveal an essential role of IFT-B, KIF17, and Rab23 in delivering specific receptors to primary cilia.
Appropriate physiological signaling by primary cilia depends on the specific targeting of particular receptors to the ciliary membrane, but how this occurs remains poorly understood. In this study, we show that D1-type dopaminergic receptors are delivered to cilia from the extra-ciliary plasma membrane by a mechanism requiring the receptor cytoplasmic tail, the intraflagellar transport complex-B (IFT-B), and ciliary kinesin KIF17. This targeting mechanism critically depends on Rab23, a small guanine nucleotide binding protein that has important effects on physiological signaling from cilia but was not known previously to be essential for ciliary delivery of any cargo. Depleting Rab23 prevents dopamine receptors from accessing the ciliary membrane. Conversely, fusion of Rab23 to a non-ciliary receptor is sufficient to drive robust, nucleotide-dependent mis-localization to the ciliary membrane. Dopamine receptors thus reveal a previously unrecognized mechanism of ciliary receptor targeting and functional role of Rab23 in promoting this process.