Electrochemical adsorption of hydrogen on mixed Pd2Pt nanostructures.
In the present contribution we have focused on the electrochemical adsorption of a proton from the solution-the Volmer reaction-on a variety of systems based on bimetallic nanostructures-clusters and wires-of Pd and Pt deposited on a surface of Au(111). We have calculated the free energy surface for the electron transfer step by a combination of DFT calculations, MD simulations and the theory of electrocatalysis. We analyze in detail the interaction of the metal d band with the valence orbital of the hydrogen and its effect on the catalytic activity as well as several aspects that influence the electrode reactivity such as spatial arrangements of the nanostructures, the solvation shell and chemical factors. We found that the mixed Pd2Pt wire interacts strongly with hydrogen, and retains an almost complete solvation shell, which is reflected in a substantially reduced activation energy for the Volmer step. Thus, Pd2Pt wires on Au(111) are predicted to be efficient electrocatalysts for the reaction.


Fining of Red Wine Monitored by Multiple Light Scattering.
This work describes a new approach based on multiple light scattering to study red wine clarification processes. The whole spectral signal (1933 backscattering points along the length of each sample vial) were fitted by a multivariate kinetic model that was built with a three-step mechanism, implying (1) adsorption of wine colloids to fining agents, (2) aggregation into larger particles, and (3) sedimentation. Each step is characterized by a reaction rate constant. According to the first reaction, the results showed that gelatin was the most efficient fining agent, concerning the main objective, which was the clarification of the wine, and consequently the increase in its limpidity. Such a trend was also discussed in relation to the results achieved by nephelometry, total phenols, ζ-potential, color, sensory, and electronic nose analyses. Also, higher concentrations of the fining agent (from 5 to 30 g/100 L) or higher temperatures (from 10 to 20 °C) sped up the process. Finally, the advantage of using the whole spectral signal vs classical univariate approaches was demonstrated by comparing the uncertainty associated with the rate constants of the proposed kinetic model. Overall, multiple light scattering technique showed a great potential for studying fining processes compared to classical univariate approaches.


Body composition is associated with physical activity in daily life as measured using a triaxial accelerometer in both men and women.
Activity-related energy expenditure is the most variable component of total energy expenditure and thus an important determinant of energy balance. To determine whether body composition is related to physical activity in both men and women. A total of 134 healthy participants were recruited (80 women, 54 men; aged 21+/-2 years; body mass index, 22.0+/-2.4). Physical activity was measured for a period of 2 weeks using a triaxial accelerometer for movement registration (Tracmor). Percentage body fat (%BF) was determined by underwater weighing and deuterium dilution according to Siri's three-compartment model. The participant characteristics-body mass, height and gender together explained a substantial part of the variation in %BF (R(2)=0.75, SEE=4.0%). Adding physical activity to the model increased the explained variation in %BF with 4% (R(2)=0.79, SEE=3.7%, P<0.001). Taking seasonality into account by adding the number of daylight hours as an independent variable further increased the explained variation with 1% (R(2)=0.80, SEE=3.7%, P<0.05). In analogy, the association was evaluated for both genders separately. In women, %BF and physical activity were significantly associated (P<0.001). In men, %BF was only associated with physical activity when seasonality was taken into account as well (P<0.05). This probably resulted from men participating more in season bound sports, because an association was found without adjusting for seasonality when only men with a consistent year-round participation in sports were considered. Evidence was found for an association between body composition and physical activity in both genders. A consistent year-round degree of physical activity appears to be a prerequisite to reveal the association. Moreover, Tracmor-assessed physical activity improves the estimate of %BF when a participant's characteristics are taken into account.


Magnetotactic Bacteria and Magnetosomes as Smart Drug Delivery Systems: A New Weapon on the Battlefield with Cancer?
An important direction of research in increasing the effectiveness of cancer therapies is the design of effective drug distribution systems in the body. The development of the new strategies is primarily aimed at improving the stability of the drug after administration and increasing the precision of drug delivery to the destination. Due to the characteristic features of cancer cells, distributing chemotherapeutics exactly to the microenvironment of the tumor while sparing the healthy tissues is an important issue here. One of the promising solutions that would meet the above requirements is the use of Magnetotactic bacteria (MTBs) and their organelles, called magnetosomes (BMs). MTBs are commonly found in water reservoirs, and BMs that contain ferromagnetic crystals condition the magnetotaxis of these microorganisms. The presented work is a review of the current state of knowledge on the potential use of MTBs and BMs as nanocarriers in the therapy of cancer. The growing amount of literature data indicates that MTBs and BMs may be used as natural nanocarriers for chemotherapeutics, such as classic anti-cancer drugs, antibodies, vaccine DNA, and siRNA. Their use as transporters increases the stability of chemotherapeutics and allows the transfer of individual ligands or their combinations precisely to cancerous tumors, which, in turn, enables the drugs to reach molecular targets more effectively.


Information and Communication Technology Based Integrated Care for Older Adults: A Scoping Review.
Integrated care is an important initiative to respond positively to the ageing of society and information and communication technology(ICT) plays an important role in facilitating the integration of functional and normative health and social care. The scoping review aims to synthesize evidence on the experience and practice of ICT-based implementation of integrated care for older adults. This study followed the research framework developed by Arksey and O'malley for the scoping review and systematically searched for relevant studies published between 1 January 2000 and 30 March 2022 from nine electronic databases, three specialist journals, three key institutional websites, 11 integrated care project websites, google scholar and references of the studies to be included. Two reviewers independently screened and extracted data and used thematic analysis to sort out and summarize the core elements, hindrances and facilitators of ICT-based integrated care. A total of 77 studies were included in this study, including 36 ICT-based practice models of integrated care with seven core elements of implementation including single entry point, comprehensive geriatric assessment, personalized care planning, multidisciplinary case conferences, coordinated care, case management and patient empowerment, which generally had a positive effect on improving quality of life, caregiver burden and primary care resource utilization for older adults, but effectiveness evaluations remained Heterogeneity exists. The barriers and facilitators to ICT-based implementation of integrated care were grouped into four themes: demand-side factors, provider factors, technology factors and system factors. The implementation of ICT-based integrated care for the elderly is expected to improve the health status of both the supply and demand of services, but there is still a need to strengthen the supply of human resources, team training and collaboration, ICT systems and financial support in order to promote the wider use of ICT in integrated care.


Bromodeoxyuridine amplifies free-radical-mediated DNA damage.
Elevated oxygen concentrations and paraquat, a superoxide-generating compound, induce an arrest of cells in the G2 phase of the cell cycle, which can be enhanced by adding bromodeoxyuridine (BrdU) to the culture medium. Experiments with the lipophilic peroxide cumene hydroperoxide and the free-radical scavenger vitamin E demonstrate that the BrdU-dependent G2 arrest is not mediated by lipid peroxidation. The BrdU-dependency of arrest in the G2 phase can be used as a sensitive cell biological assay to detect DNA damage elicited by oxygen free radicals.


Class II major histocompatibility complex (Ia) antigen-bearing dendritic cells within the iris and ciliary body of the rat eye: distribution, phenotype and relation to retinal microglia.
The density, distribution and surface phenotype of dendritic cells (DC) and macrophage populations within the ciliary body and iris of Wistar Furth rats were studied by a combination of flat mounting, tangential sectioning, pre-embedding fixation, with a single and double immunohistochemical techniques. Monoclonal antibodies included anti-Ia (OX6) and other dendritic cell/macrophage (ED1 and ED8) or mature tissue macrophage markers (ED2). Single and double staining revealed a network (approximately 400 cells/mm2) of Ia+ cells within the epithelium of the ciliary processes with the morphological and surface phenotypic characteristics of DC populations in other tissues. A minor proportion of DC co-expressed ED1 and ED8, but not ED2. In contrast the immunopositive cells in the lamina propria displayed a more generalized phenotype, including ED2 expression, and pleiomorphic morphology suggesting a preponderance of cells of macrophage lineage. Flat mounts of iris revealed a remarkably regular network of Ia+ DC at a density of 450 cells/mm2. The network of DC in the ciliary epithelium terminated at the cilioretinal junction where they formed a continuous syncytium with retinal microglia which did not display Ia staining. The demonstration of networks of cells with relevant morphological and phenotypical properties of professional antigen-presenting cells at strategic locations within the eye has important implications in relation to ocular immune regulation and on the theories of the mechanism of anterior chamber-associated immune deviation (ACAID). Namely, until now it has been assumed that 'immune privilege' in the anterior chamber of the eye is partly a consequence of there being a paucity of class II+ cells in the surrounding tissues. Dendritic cells in the eye may function as antigen-presenting cells, sampling endogenous and exogenous intraocular antigens and possibly migrating from the eye to draining lymphoid organs (the spleen) where they may generate systemic immune responses. Equally dendritic cells could potentially regulate local immune responses for example in various forms of autoimmune uveoretinal inflammatory disease.


Does proximal rectus femoris release influence kinematics in patients with cerebral palsy and stiff knee gait?
Stiff gait resulting from rectus femoris dysfunction in cerebral palsy commonly is treated by distal rectus femoris transfer (DRFT), but varying outcomes have been reported. Proximal rectus femoris release was found to be less effective compared with DRFT. No study to our knowledge has investigated the effects of the combination of both procedures on gait. We sought to determine whether an additional proximal rectus release affects knee and pelvic kinematics when done in combination with DRFT; specifically, we sought to compare outcomes using the (1) range of knee flexion in swing phase, (2) knee flexion velocity and (3) peak knee flexion in swing phase, and (4) spatiotemporal parameters between patients treated with DRFT, with or without proximal rectus release. Furthermore the effects on (5) anterior pelvic tilt in both groups were compared. Twenty patients with spastic bilateral cerebral palsy treated with DRFT and proximal rectus femoris release were matched with 20 patients in whom only DRFT was performed. Standardized three-dimensional gait analysis was done before surgery, at 1 year after surgery, and at a mean of 9 years after surgery. Basic statistics were done to compare the outcome of both groups. The peak knee flexion in swing was slightly increased in both groups 1 year after surgery, but was not different between groups. Although there was a slight but not significant decrease found the group with DRFT only, there was no significant difference at long-term followup between the groups. Timing of peak knee flexion, range of knee flexion, and knee flexion velocity improved significantly in both groups, and in both groups a slight deterioration was seen with time; there were no differences in these parameters between the groups at any point, however. There were no group differences in spatiotemporal parameters at any time. There were no significant differences in the long-term development of anterior pelvic tilt between the groups. The results of our study indicate that the short- and long-term influences of adding proximal rectus femoris release on the kinematic effects of DRFT and on pelvic tilt in children with cerebral palsy are negligible. Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


Cardiac Arrest Secondary to Inferior ST-Segment-Elevation Myocardial Infarction in Patient with Paroxysmal Nocturnal Hemoglobinuria and COVID-19 Infection.
Patients with paroxysmal nocturnal hemoglobinuria (PNH) have transient attacks of complement-mediated hemolysis and thrombosis that can be spontaneous or secondary to precipitating factors such as infections. We present a case of a 63-year-old male patient with a medical history of PNH who presented with typical chest pain, fever, cough, jaundice, and dark-colored urine. On examination, he was hemodynamically stable but had conjunctival icterus. A few minutes after presentation, the patient suffered a ventricular fibrillation cardiac arrest and then achieved a return of spontaneous circulation after receiving two defibrillator shocks. EKG showed inferior wall ST-segment elevation myocardial infarction. Labs showed hemoglobin of 6.4 g/dl, elevated cardiac markers, serum lactate dehydrogenase, and indirect bilirubin. Serum haptoglobin was < 1 mg/dl. His COVID-19 polymerase chain reaction test was positive. Immediately, the patient received 2 units of packed RBCs and underwent a coronary angiogram (CA), which revealed total proximal occlusion of the right coronary artery. He underwent successful percutaneous coronary intervention (PCI), and two drug-eluting stents were placed. His peripheral blood immunophenotyping and flow cytometry showed loss of glycosylphosphatidylinositol-linked antigens and decreased expression of CD 59/14/24. He was started on ravulizumab, a humanized monoclonal antibody complement five inhibitor. Both PNH and COVID-19 increase the risk of thrombosis. Endothelial injury and cytokine storm increase the risk of thrombosis in COVID-19 patients, whereas the activation of the coagulation system and the impairment of the fibrinolytic system by complement cascade leads to thrombosis in PNH patients. Regardless of which pathway leads to coronary artery thrombosis, CA and PCI can be life-saving.


Male reproductive success in a promiscuous mammal: behavioural estimates compared with genetic paternity.
Molecular techniques have enabled behavioural ecologists to reassess mating systems from a genetic perspective. Studies of paternity frequently reveal that mating behaviour does not always reflect parentage, and may bring to light alternative mating tactics. Here we present a comparison of behavioural and genetic measures of male reproductive success in a mammalian mating system in which both sexes are highly promiscuous. Rather than having a stable harem social structure, Soay rams (Ovis aries) on the island of Hirta, St Kilda, UK usually consort with individual oestrous ewes sequentially. Not all matings occur between consort pairs, however, and ewes have been seen to mate with up to 10 different rams on the same day. Using locus-specific polymorphism at five protein and 10 microsatellite DNA loci, we determined paternity for 236 lambs born into three cohorts, and compared paternity with estimates of mating success derived from more than one census of rutting behaviour. The correlation between the number of ewes with which each ram was witnessed in consort and the number of paternities assigned was positive and statistically significant, and rams that were observed in consort with a ewe were 18 times more likely to have sired her offspring than other candidate rams. However, most lambs (73%) were not sired by a ram seen in consort with the oestrous mother. Many juveniles, yearlings and some adult rams were rarely seen in consort with ewes, yet were assigned a significant number of paternities. These results suggest that mating tactics differ between age groups, and that alternative mating strategies among adults that do not involve forming consorts with many females also confer mating success. For these reasons, census-based observations of consort associations between individuals cannot be used to accurately estimate individual male reproductive success in this population.


The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases.
A combination of in vivo and in vitro assays was employed to describe the ligand-independent interaction of the orphan nuclear receptor TR2 and histone deacetylase proteins. The repressive effect of TR2 on transcription of a luciferase reporter driven by a promoter containing a direct repeat-5 (DR5) derived from the human RARbeta gene was suppressed by the addition of the histone deacetylase inhibitor trichostatin A. Immunoprecipitation with FLAG-epitope (MDYKDDDDK)-tagged histone deacetylase proteins was used to demonstrate that TR2 and histone deacetylases 3 or 4 are present in the same immunoprecipitated complex. Deacetylase activity was demonstrated for these coimmunoprecipitates, further confirming the in vivo interaction of TR2 and histone deacetylases. Immunoprecipitation with anti-TR2 antibody was used to demonstrate interaction of TR2 with endogenously expressed histone deacetylases 3 and 4 in COS-1 cells. Dissection of TR2 domains showed that the DNA binding domain of the receptor was responsible for interaction with both histone deacetylases 3 and 4 in glutathione-S-transferase pull-down assays, while the ligand binding domain did not interact. The pull-down data were confirmed with far Western blots that also showed a direct interaction between labeled histone deacetylase proteins and TR2. It is suggested that repression mediated by unliganded TR2 is mediated, in part, by a direct interaction of this receptor with histone deacetylase proteins.


Accuracy of Pretransplant Imaging Diagnostic for Hepatocellular Carcinoma: A Retrospective German Multicenter Study.
Selection and prioritization of patients with HCC for LT are based on pretransplant imaging diagnostic, taking the risk of incorrect diagnosis. According to the German waitlist guidelines, imaging has to be reported to the allocation organization (Eurotransplant) and pathology reports have to be submitted thereafter. In order to assess current procedures we performed a retrospective multicenter analysis in all German transplant centers with focus on accuracy of imaging diagnostic and tumor classification. 1168 primary LT for HCC were conducted between 2007 and 2013 in Germany. Patients inside the Milan, UCSF, and up-to-seven criteria were misclassified with definitive histologic results in 18%, 15%, and 11%, respectively. Patients pretransplant outside the Milan, UCSF, and up-to-seven criteria were otherwise misclassified in 34%, 43%, and 41%. Recurrence-free survival correlated with classification by posttransplant histological report, but not pretransplant imaging diagnostic. Univariate analysis revealed tumor size, vascular invasion, and grading as significant parameters for outcome, while tumor grading was the only parameter persisting by multivariate testing. Conclusion. There was a relevant percentage (15-40%) of patients misclassified by imaging diagnosis at a time prior to LI-RADS and guidelines to improve imaging of HCC. Outcome analysis showed a good correlation to histological, in contrast poor correlation to imaging diagnosis, suggesting an adjustment of the LT selection and prioritization criteria.


Timing and causes of death after endovascular thrombectomy in patients with acute ischemic stroke.
Endovascular thrombectomy (EVT) increases the chance of good functional outcome after ischemic stroke caused by a large vessel occlusion, but the risk of death in the first 90 days is still considerable. We assessed the causes, timing and risk factors of death after EVT to aid future studies aiming to reduce mortality. We used data from the MR CLEAN Registry, a prospective, multicenter, observational cohort study of patients treated with EVT in the Netherlands between March 2014, and November 2017. We assessed causes and timing of death and risk factors for death in the first 90 days after treatment. Causes and timing of death were determined by reviewing serious adverse event forms, discharge letters, or other written clinical information. Risk factors for death were determined with multivariable logistic regression. Of 3180 patients treated with EVT, 863 (27.1%) died in the first 90 days. The most common causes of death were pneumonia (215 patients, 26.2%), intracranial hemorrhage (142 patients, 17.3%), withdrawal of life-sustaining treatment because of the initial stroke (110 patients, 13.4%) and space-occupying edema (101 patients, 12.3%). In total, 448 patients (52% of all deaths) died in the first week, with intracranial hemorrhage as most frequent cause. The strongest risk factors for death were hyperglycemia and functional dependency before the stroke and severe neurological deficit at 24-48 h after treatment. When EVT fails to decrease the initial neurological deficit, strategies to prevent complications like pneumonia and intracranial hemorrhage after EVT could improve survival, as these are often the cause of death.


The Aurora kinase Ipl1 is necessary for spindle pole body cohesion during budding yeast meiosis.
In budding yeast, the microtubule-organizing center is called the spindle pole body (SPB) and shares structural components with the centriole, the central core of the animal centrosome. During meiotic interphase I, the SPB is duplicated when DNA replication takes place. Duplicated SPBs are linked and then separate to form a bipolar spindle required for homolog separation in meiosis I. During interphase II, SPBs are duplicated again, in the absence of DNA replication, to form four SPBs that establish two spindles for sister-chromatid separation in meiosis II. Here, we report that the Aurora kinase Ipl1, which is necessary for sister-chromatid cohesion, is also required for maintenance of a tight association between duplicated SPBs during meiosis, which we term SPB cohesion. Premature loss of cohesion leads to SPB overduplication and the formation of multipolar spindles. By contrast, the Polo-like kinase Cdc5 is necessary for SPB duplication and interacts antagonistically with Ipl1 at the meiotic SPB to ensure proper SPB separation. Our data suggest that Ipl1 coordinates SPB dynamics with the two chromosome segregation cycles during yeast meiosis.


Evidence for MHC gene control of lesion severity in experimental allergic encephalomyelitis of chickens.
Susceptibility to experimental allergic encephalomyelitis (EAE) was studied in two related inbred lines of chickens (lines G-B1 and G-B2) as well as their F2 generation offspring. MHC (B system) genotypes of G-B1 and G-B2 birds are B13/B13 and B6/B6, respectively. Sensitization with central nervous system (CNS) tissue failed to induce clinical symptoms in any of the birds. However, brain lesions typical for EAE were found to be significantly greater in line G-B1 birds than in line G-B2 birds. Evidence for MHC gene control of EAE brain lesion severity was found with F2 offspring. Mean lesion scores were lowest for B6/B6 birds, intermediate for B6/B13 birds, and highest for B13/B13 birds.


Implantable Neural Electrodes Fabrication Based on Perfluoroalkoxyalkane Film.
Objective:In this paper, the fabrication of perfluoro-alkoxy alkane (PFA) film-based planar neural electrodes was proposed. The fabrication of PFA-based electrodes started with cleaning of PFA film. The argon plasma pretreatment was performed on the PFA film surface and attached to a dummy silicon wafer. Metal layers were deposited and patterned using the standard Micro Electro Mechanical Systems (MEMS) process. Electrode-sites and pads were opened using reactive ion etching (RIE). Lastly, the electrode patterned PFA substrate film was thermally laminated with the other bare PFA film. Electrical-physical evaluation tests were conducted along with in vitro tests, ex vivo tests and soak tests to evaluate the electrode performance and biocompatibility. The electrical and physical performance of PFA-based electrodes had better performances compared to other biocompatible polymer-based electrodes. Also, the biocompatibility and longevity were verified by cytotoxicity test, elution test, and accelerated life test. The PFA film-based planar neural electrode fabrication was established and evaluated. The PFA based electrodes showed excellent benefits such as long-term reliability, low water absorption rate, and flexibility using the neural electrode. For implantable neural electrodes, hermetic sealing is required for in vivo durability. PFA fulfilled a low water absorption rate with relatively low Young's modulus to increase the longevity and biocompatibility of the devices.


CBF oscillations induced by trigeminal nerve stimulation protect the pericontusional penumbra in traumatic brain injury complicated by hemorrhagic shock.
Traumatic peri-contusional penumbra represents crucial targets for therapeutic interventions after traumatic brain injury (TBI). Current resuscitative approaches may not adequately alleviate impaired cerebral microcirculation and, hence, compromise oxygen delivery to peri-contusional areas. Low-frequency oscillations in cerebral blood flow (CBF) may improve cerebral oxygenation in the setting of oxygen deprivation. However, no method has been reported to induce controllable oscillations in CBF and it hasn't been applied as a therapeutic strategy. Electrical stimulation of the trigeminal nerve (TNS) plays a pivotal role in modulating cerebrovascular tone and cerebral perfusion. We hypothesized that TNS can modulate CBF at the targeted frequency band via the trigemino-cerebrovascular network, and TNS-induced CBF oscillations would improve cerebral oxygenation in peri-contusional areas. In a rat model of TBI complicated by hemorrhagic shock, TNS-induced CBF oscillations conferred significant preservation of peri-contusional tissues leading to reduced lesion volume, attenuated hypoxic injury and neuroinflammation, increased eNOS expression, improved neurological recovery and better 10-day survival rate, despite not significantly increasing CBF as compared with those in immediate and delayed resuscitation animals. Our findings indicate that low-frequency CBF oscillations enhance cerebral oxygenation in peri-contusional areas, and play a more significant protective role than improvements in non-oscillatory cerebral perfusion or volume expansion alone.


Infected hepatic cyst complicating urinary sepsis.
Congenital hepatic cysts are a common disorder. Usually they are asymptomatic and do not have to be treated. However, some serious complications can occur. We report here the case of an 86-year old patient who has been treated by a percutaneous drainage for an infected solitary hepatic cyst due to urinary sepsis. She was admitted to the Department of Internal Medicine for epigastric pain with fever and chills. The patient was treated for a urinary tract infection 3 weeks ago by her General Practitioner. On admission, blood tests showed 21 620 neutrophils per microliter with a C-reactive protein level at 443.7 mg/L, procalcitonin > 200 ng/mL, total bilirubin at 1.43 mg/dL, lactate dehydrogenase at 666 U/L and alanine aminotransferase at 227 U/L. Urinalysis and hemocultures highlighted the presence of Escherichia coli and Streptococcus constellatus. The abdominal tomodensitometry indicated the presence of a left hepatic biliary cyst with banal appearance. She was first treated with intravenous amoxicillin clavulanic acid. After a few days, another abdominal tomodensitometry with contrast pinpointed a large abscess of 11 centimeters in diameter extending to liver segments II and IV with a similar small lesion in segments IV and V. clindamycin per os was added to the treatment because of its good diffusion in tissues. Percutaneous drain was inserted under tomodensitometric control and stayed in place until the follow-up at three weeks. Bacteriologic culture on the fluid sample demonstrated the presence of Escherichia coli and Streptococcus constellatus. The abscess completely regressed after 6 weeks of treatment and the biologic abnormalities resolved at the same time.


Broadband electrical characterization of multiwalled carbon nanotubes and contacts.
The electrical response of an individual multiwalled carbon nanotube (MWNT) and its contacts, welded to a coplanar waveguide (CPW), was measured up to 24 GHz using a technique that removes environment effects. This is the first time MWNT contact effects have been systematically isolated from the CPW. Each contact response was quite different and also showed a pronounced sensitivity to ambient light. Adding more contact material clearly changed the high-frequency electrical response and the sensitivity to light.


A predictive model for respiratory distress in patients with COVID-19: a retrospective study.
Coronavirus disease 2019 (COVID-19), associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global public health crisis. We retrospectively evaluated 863 hospitalized patients with COVID-19 infection, designated IWCH-COVID-19. We built a successful predictive model after investigating the risk factors to predict respiratory distress within 30 days of admission. These variables were analyzed using Kaplan-Meier and Cox proportional hazards (PHs) analyses. Hazard ratios (HRs) and performance of the final model were determined. Neutrophil count >6.3×109/L, D-dimer level ≥1.00 mg/L, and temperature ≥37.3 °C at admission showed significant positive association with the outcome of respiratory distress in the final model. Complement C3 (C3) of 0.9-1.8 g/L, platelet count >350×109/L, and platelet count of 125-350×109/L showed a significant negative association with outcomes of respiratory distress in the final model. The final model had a C statistic of 0.891 (0.867-0.915), an Akaike's information criterion (AIC) of 567.65, and a bootstrap confidence interval (CI) of 0.866 (0.842-0.89). This five-factor model could help in early allocation of medical resources. The predictive model based on the five factors obtained at admission can be applied for calculating the risk of respiratory distress and classifying patients at an early stage. Accordingly, high-risk patients can receive timely and effective treatment, and health resources can be allocated effectively.


Endothelin stimulation of cytosolic calcium and gonadotropin secretion in anterior pituitary cells.
The presence of endothelin, a vasoconstrictor peptide, in the hypothalamus and posterior pituitary suggests that it also regulates neural and other nonvascular target cells. In pituitary gonadotrophs, low doses of endothelin evoked oscillations in the intracellular calcium concentration, and high doses induced a biphasic calcium response. Mobilization of intracellular calcium predominated during the spike phase of the calcium response to endothelin, whereas calcium entry through dihydropyridine-sensitive channels contributed to both the spike and plateau phases of the calcium response. Endothelin was a potent as hypothalamic gonadotropin-releasing hormone (GnRH) in stimulation of gonadotropin release in perifused pituitary cells. Endothelin bound specifically to pituitary cells with a dissociation constant of 70 picomolar, and induced rapid formation of inositol trisphosphate and diacyglycerol. Although intracellular calcium concentration and gonadotropin secretory responses to endothelin were independent to the GnRH receptor, endothelin and GnRH appeared to have a common signal transduction mechanism. These observations suggest that endothelin can act as a neuropeptide to regulate anterior pituitary function.


Gut microbiome is associated with asthma and race in children with food allergy.
The composition of the gut microbiome has been associated with development of atopic conditions such as food allergy (FA) and asthma. African American or Black children with FA have higher rate of asthma compared to their White counterparts. We sought to investigate whether the diversity and relative abundance (RA) of gut microbiota is different between children with FA from different racial backgrounds living in the same cities. Furthermore, we aimed to understand whether the difference in the gut microbiota is associated with asthma in children with FA. We analyzed and compared the stool microbiome of a cohort of Black and White children with FA by shotgun genomic sequencing. A total of 152 children with IgE-mediated FA enrolled onto FORWARD (Food Allergy Outcomes Related to White and African American Racial Differences); 30 Black and 122 White children were included. The RA of several bacteria was associated with race and asthma. Most notably the RA of Bacteroides thetaiotaomicron, Chlamydia thrachomatis, Parabacteroides goldsteinii, and Bacteroides eggerthii were significantly higher, while the RA of Bifidobacterium sp CAG:754, Parabacterium johnsonii, Bacteroides intestinalis, and Bifidobacterium breve were significantly lower in stool samples of Black children compared to White children. Asthma was associated with lower RA of B breve, Bifidobacterium catenulatum, Prevotella copri, Veilloella sp CAG:933, and Bacteroides plebius, and higher RA of 3 Bacteroides species. The observed variations in the gut microbiota of Black and White children such as differences in the Bacteroides and Bifidobacterium species along with their association to history of asthma in our cohort is indicative of their potential role in the higher rate of asthma observed among Black children with FA.


r-BRICS - a revised BRICS module that breaks ring structures and carbon chains.
Molecular fragmentation has been frequently used for machine learning, molecular modeling, and drug discovery studies. However, the current molecular fragmentation tools often lead to large fragments that are useful to limited tasks. Specifically, long aliphatic chains, certain connected ring structures, fused rings, as well as various nitrogen-containing molecular entities often remain intact when using BRICS. With no known methods to solve this issue, we find that the fragments taken from BRICS are inflexible for tasks such as fragment-based machine learning, coarse-graining, and ligand-protein interaction assessment. In this work, we develop a revised BRICS (r-BRICS) module that allows more flexible fragmentation on a wider variety of molecules. We show that r-BRICS generates smaller fragments than BRICS, allowing localized fragment assessments. Furthermore, r-BRICS generates a fragment database with significantly more unique small fragments than BRICS, which is potentially useful for fragmentbased drug discovery.


Management of deliberate self harm in general practice: a qualitative study.
It has been estimated that the incidence of deliberate self harm (DSH) is at least 10 times that of suicide. Accident and emergency discharge figures also point to an almost doubling of reported cases of DSH in the early 1990s. To assess general practitioners' (GPs') views on, and educational requirements for, managing patients following an episode of DSH. A qualitative study with 14 GPs (seven male and seven female) from two outer-London boroughs, selected in order to provide a maximum variety sample. Interviews took place between February and April 1997, and data were analyzed using the principles of grounded theory. Most GPs felt that all patients presenting with DSH should be assessed by a psychiatrist. They expressed a preference for working with a community psychiatric nurse rather than a counsellor. Suggestions to improve their working relationship with community mental health teams included provision of one centralized point of referral and ease of access to the service in times of crisis. GPs were sceptical of guidelines, emphasizing that they needed joint ownership in writing them, but most importantly that they needed adequate resources to implement them. Specific changes to postgraduate education were suggested, such as individual educational portfolios. Improved working relationships between GPs and community mental health teams are needed in order to provide a more efficient and effective service for patients. Lifelong learning needs to be adapted in a style and approach to suit GPs' individual requirements.


Task-specific modulation of multi-digit forces to object texture.
During multi-digit grasping both local and non-local digit force responses occur in response to changes in texture at selected digits depending on the grasp configuration. However, the extent to which the specific patterns of force distribution depend on the requirement to hold the object against gravity remains to be determined. In the present study, we examined whether grasp force sharing patterns are invariant when the constraint of maintaining the object orientation vertical against gravity is removed. We used changes in object texture to elicit force changes at single digits during two grasping tasks with different behavioral contexts. One task entailed holding an object against gravity (object hold [OH]). A second (force production [FP]) task consisted of generating lifting forces on an object clamped to the tabletop that were matched to those used during OH. Unlike OH, the FP task lacks the behavioral consequences associated with erroneous sharing of normal and tangential digit forces, e.g., object tilt. Ten subjects lifted and simulated lifting an instrumented object measuring grasping normal and vertical tangential forces at all five digits when the textures were uniformly high-friction sandpaper or low-friction rayon and when one digit contacted a different frictional texture than the other four digits. We found that in both tasks texture changes at individual digits elicited force changes at that digit as well as other digits. However, the specific pattern of force distribution changes differed during OH compared to FP. While subjects modulate the normal and tangential digit forces to different degrees depending on object texture and the grasping task, they ignore the requirement of moment equilibrium when this has no consequences on object orientation (FP task). These findings indicate that multi-digit force responses to texture revealed by previous studies are not obligatory and suggest that the behavioral context of a task should be considered when inferring general principles of multi-digit force coordination.


[The role of phototherapy in the rehabilitation of newborn babies and infants].
This review is devoted to the problems pertaining to the rational application of phototherapy in the rehabilitation of newborn babies and infants. The analysis of the classical and present-day literature sources provided materials for the development of the rationale for the use of colour-puncture therapy. The data included in this review indicate that phototherapy has positive effect on the immune and rehabilitative processes in the newborns following surgical interventions and in the breast-fed infants suffering hypoxic ischemic encephalopathy. Phototherapy is equally beneficial when the newborn babies need to be treated for cutaneous and nervous disorders or undergo a surgical operation. Moreover, it can be applied to manage endocrine disorders and diseases of the vegetative nervous system. The photo-induced changes in the skin influence the concentration of biologically active compounds in the systemic circulation. It is believed that colour-puncture therapy makes it possible to selectively affect biologically active points in the channel-meridian system of the newborn babies and infants.


Comparative aroma and taste profiles of oil furu (soybean curd) fermented with different mucor strains.
The effects of different mucor strains (Mucor racemosus, Actinomucor, and Mucor wutungkiao) on aroma and taste profiles based on proteolysis, lipolysis, and their catabolism in oil furu were studied. Gas chromatography-mass spectrometry and relative odor activity were used to monitor the changes of key volatile compounds and the differences in the characteristic aroma contents of oil furu. Using principal component analysis, the different fermentation strains had an effect on aroma profiles. The volatile compounds from metabolism of protein and fatty acid contributed to the aroma of oil furu with different contribution from the different strains, presumably due to their different enzymes. The electronic tongue and free amino acid profiles also showed strain differences of taste. Based on these results, optimization of the amount of each of the different mucor strains during cofermentation might achieve better flavor.


Effects of Zinc Source and Enzyme Addition on the Fecal Microbiota of Dogs.
Supplemental zinc from organic sources has been suggested to be more bioavailable than inorganic ones for dog foods. However, the bioavailability of zinc might be affected by dietary constituents such as phytates. The present study aimed to evaluate the effects of two zinc sources (zinc sulfate and zinc proteinate) and the addition of a multi-enzymatic complex from the solid-state fermentation of Aspergillus niger on end-products of fecal fermentation and fecal microbiota of adult Beagles fed a high-phytate diet. The experimental design consisted of three 4 × 4 Latin Squares with a 2 × 2 factorial arrangement of treatments (n = 12 Beagles), with four periods and four diets: zinc sulfate without (IZ) or with (IZ +) enzyme addition, and zinc proteinate without (OZ) or with (OZ +) enzyme addition. Enzyme addition significantly affected Faith's phylogenetic diversity index, whereas zinc source did not affect either beta or alpha diversity measures. Linear discriminant analysis effect size detected nine taxa as markers for organic zinc, 18 for inorganic source, and none for enzyme addition. However, with the use of a negative binomial generalized linear model, further effects were observed. Organic zinc was associated with a significantly higher abundance of Firmicutes and lower Proteobacteria and Bacteroidetes, although at a genus level, the response varied. The DNA abundance of Clostridium cluster I, Clostridium cluster XIV, Campylobacter spp., Ruminococcaceae, Turicibacter, and Blautia was significantly higher in dogs fed IZ and IZ + diets. Higher abundance of genus Lactobacillus was observed in dogs fed enzyme-supplemented diets. End-products of fecal fermentation were not affected by zinc source or enzymes. An increase in some taxa of the phyla Actinobacteria and Firmicutes was observed in feces of dogs fed organic zinc with enzyme addition but not with inorganic zinc. This study fills a gap in knowledge regarding the effect of zinc source and enzyme addition on the fecal microbiota of dogs. An association of zinc bioavailability and bacteria abundance is suggested, but the implications for the host (dog) are not clear. Further studies are required to unveil the effects of the interaction between zinc sources and enzyme addition on the fecal microbial community.


USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24.
Reprogramming of macrophages toward an M1 phenotype is a novel strategy to induce anticancer immunity. However, the regulatory mechanisms of M1 macrophage polarization and its functional roles in nasopharyngeal carcinoma (NPC) progression need to be further explored. Here we found that SPLUNC1 was highly expressed and responsible for M1 macrophage polarization. JAK/STATs pathway activation was involved in SPLUNC1-mediated M1 macrophage polarization. Importantly, regulation of SPLUNC1 in macrophages affected CM-mediated influence on NPC cell proliferation and migration. Mechanistically, USP7 deubiquitinated and stabilized TRIM24, which promoted SPLUNC1 expression via recruitment of STAT3 in M1 macrophages. Depletion of TRIM24 inhibited M1 macrophage polarization, which facilitated NPC cell growth and migration. However, over-expression of USP7 exhibited the opposite results and counteracted the tumorigenic effect of TRIM24 silencing. Finally, the growth and metastasis of NPC cells in vivo were repressed by USP7-induced M1 macrophage polarization via modulating TRIM24/SPLUNC1 axis. USP7 delayed NPC progression via promoting macrophage polarization toward M1 through regulating TRIM24/SPLUNC1 pathway, providing evidence for the development of effective antitumor immunotherapies for NPC.


Management of upper extremity aneurysms: a systematic review.
The aim of this paper is to provide recommendations for diagnosis and management of arterial or venous aneurysms of the upper extremity. A systematic review of the Medline and Cockrane databases was performed from 1988 to 2019 by a combined strategy of MeSh terms. One-hundred-forty-four publications were identified: 111 addressing arterial aneurysms and 33 addressing venous aneurysms. A total of 162 cases of arterial aneurysms, mostly brachial aneurysms (34.0% of cases) and 40 cases of venous aneurysms, mostly located in the forearm (60.0% of cases) were reported. For both types of aneurysms, most common presentation was the perception of a mass (56.3% for arterial one and 87.5% for venous one), but thromboembolic complication (46.7%), paresthesia (16.5%) or rupture (6.4%) could be observed in the setting of arterial aneurysms, while arm swelling (27.5%), neurological symptoms (12.5%), pulmonary embolism (10.0%) or rupture (2.5%) could occur in the setting of venous aneurysms. DUS was performed as first imaging modality for both settings, followed but CTA and MRA, especially in arterial aneurysms, to evaluate distal emboli and surrounding vasculature. Surgical treatment was mostly based on excision of the aneurysms with revascularization for arterial aneurysms (77.2%) and resection without reconstruction for the venous one (85.0%). Complications occurred in 10.5% of the cases of arterial aneurysms, none occurred after venous aneurysm resection. Prompt diagnosis and appropriate preoperative imaging are mandatory in order to offer the best treatment modality. Open resection with revascularization seems to be the treatment of choice for arterial aneurysms, although endovascular procedures became more popular. Venous aneurysms require excision without revascularization.


[10-year experience in flexible bronchoscopy in pediatric patients].
Approximately a decade ago, pediatric Flexible Bronchoscopy (FB) was introduced in Chile, after being used for several years in adults. To describe our clinical experience in FB in a ten years period. Records of procedures done between January 1993 and September 2002 at the Pediatric Service of the Catholic University Hospital, were retrospectively reviewed. We evaluated the clinical indications for the procedures in relation to patient's age and the correlation between indications and FB findings. A total of 700 procedures were performed during the period, 59% in men and 53% in patients younger than 1 year. Seventy seven percent of procedures were done in an examination room, using a nasal approach. The main indication was visualization of the airway (49%). The most common clinical diagnosis, in descending order were: atelectasis, stridor and etiologic study of pneumonia by bronchoalveolar lavage (BAL). In children younger than 6 months the most common clinical diagnosis was stridor, followed by atelectasis. The main diagnosis in the whole sample, reached by FB was atelectasis secondary to mucous plug. In children younger than 6 months, the main diagnosis was laryngomalacia. A positive microbial culture was obtained in 43% of patients in whom BAL was done. Complications were uncommon (5%) and mostly mild. In 2.3% of cases, these were severe, such as bronchospasm and need for mechanical ventilation. Severe complications were observed in patients younger than 3 months with severe stridor or in children with cancer, who required FB and BAL. Flexible bronchoscopy is a safe and useful procedure in pediatric patients.


Fecal prevalence and diversity of Salmonella species in lactating dairy cattle in four states.
Salmonella is one of the most serious foodborne pathogenic bacteria in the United States, causing an estimated 1.3 million human illnesses each year. Dairy cows can be reservoirs of foodborne pathogenic bacteria, including Salmonella spp.; it is estimated that from 27 to 31% of dairy herds across the United States are colonized by Salmonella. The present study was designed to examine the occurrence of Salmonella spp. on dairies and to examine the serotypic diversity of Salmonella isolates on sampled dairies from across the United States. Fecal samples (n = 60 per dairy) were collected from 4 dairies in each of 4 states for a total of 960 fecal samples representing a total population of 13,200 dairy cattle. In the present study, 93 of 960 samples (9.96%) collected were culture-positive for Salmonella enterica. At least one Salmonella fecal-shedding cow was found in 9 of the 16 herds (56%) and the within-herd prevalence varied in our study from 0% in 7 herds to a maximum of 37% in 2 herds, with a mean prevalence among Salmonella-positive herds of 17%. Seventeen different serotypes were isolated, representing 7 different Salmonella serogroups. There were 2 or more different serogroups and serotypes present on 7 of the 9 Salmonella-positive farms. Serotypes Montevideo and Muenster were the most frequent and widespread. From our data, it appears that subclinical colonization with Salmonella enterica is relatively common on dairy farms and is represented by diverse serotypes on US dairy farms.


Double-blind assessment of tienilic acid in essential hypertension.
The antihypertensive effectiveness of tienilic acid in doses of 250 mg once and twice daily was compared to hydrochlorothiazide 50 mg once and twice per day in a randomized double-blind trial lasting six weeks. Blood pressure fell significantly and to a similar extent with the larger dose of both drugs. This was accompanied by a slight decrease in body weight and serum potassium concentration and a slight increase in serum creatinine and blood urea nitrogen. The magnitude of these changes was similar with both drugs. Unlike hydrochlorothiazide, however, the administration of tienilic acid was associated with a marked drop in the concentration of serum uric acid. No disturbing side effects or evidence of serious toxicity were noted during treatment with the new drug.


Transoral endoscopic parathyroidectomy vestibular approach (TOEPVA) for primary hyperparathyroidism: Turkey's experience.
Parathyroid surgery has witnessed a significant evolution with the introduction of more efficacious preoperative localization imaging techniques and the use of rapid intraoperative parathormone assays. Parathyroid surgery can now be performed with the minimum of invasion. Through the adaptation of the transoral endoscopic thyroidectomy vestibular approach (TOETVA), the technique has now been adopted for parathyroid surgery, known as the transoral endoscopic parathyroidectomy vestibular approach (TOEPVA). We present here the initial experiences of 11 centers carrying out TOEPVA surgery in Turkey. Participating in the study were 11 centers, all of which were tertiary care institutions carrying out endocrine surgery. A retrospective review was made of 35 primary hyperparathyroidism patients who underwent the TOEPVA procedure between July 2017 and January 2020. Of the total 35 patients, 32 patients underwent the TOEPVA procedure successfully. All patients but one were female, and the mean age was 47.2 (20-73) years. According to localization studies, 18 of the lesions were lower left, 12 were lower right, 3 were upper right and 2 were upper left. The mean operative time was 116 (30-225) min, and three cases were converted to an open procedure. Simultaneous thyroidectomy was performed in seven cases. The average PTH level dropped to normal within 20 min. after the resection in all cases. The complication rate was 19% (ecchymosis, subcutaneous emphysema, nasal bleeding, surgical site infection and seroma). There were neither recurrent nerve palsies, nor mental nerve root or branch injuries. The average hospital stay was 1 day. No persistence was documented on follow up. TOEPVA is a "hidden scar" parathyroidectomy procedure that can be safely performed on parathyroid adenomas, in cases that have scar-related concerns. Having its own procedure-related complications, the procedure provides satisfactory objective results, particularly in centers experienced in endoscopic and endocrine surgery.


Harassment and Violence Among Men Who Have Sex with Men (MSM) and Hijras After Reinstatement of India's "Sodomy Law".
On December 11, 2013, the Indian Supreme Court recriminalized non-peno-vaginal sex under Sec. 377 of the Indian Penal Code (IPC), overturning a 2009 ruling that deemed IPC Sec. 377 unconstitutional. Similar "sodomy laws" in other countries have been associated with increased violence, harassment, and other discrimination against men who have sex with men (MSM) and transgender women. However, few studies have looked at the effects of such a law in an Indian context. This study examined experiences of victimization among MSM and hijra/transgender women (MSM-H) in the State of Maharashtra using a mixed-method approach. Data came from a quantitative survey and qualitative focus groups and interviews from an HIV prevention study as well as qualitative media and case reports from a local MSM-H-serving community-based organization. MSM-H in Maharashtra reported experiencing a high frequency of harassment, violence, and extortion, particularly from male sex partners met online and police. IPC Sec. 377 was implicated across qualitative sources as creating a culture of protection for harassment against MSM-H by being used directly as a tool for harassment, hindering victims of harassment from seeking legal recourse, and adversely impacting HIV and healthcare services. The reinstated IPC Sec. 377 may directly and indirectly facilitate negative health outcomes among MSM-H. Health agencies and advocates should continue to monitor the impact of IPC Sec. 377, incorporate rights-based approaches to protect MSM-H identities while addressing their health and well-being, and explore avenues to initiate discussions with the government to work toward repealing the law.


Enhancement of venous drainage with vein stripper for reversed pedicled neurocutaneous flaps.
The flaps based on the vascular axis of superficial sensitive cutaneous nerves had gained increased popularity in reconstructive surgery because of such major advantages as preservation of major extremity arteries and avoidance of microsurgical procedures. However, postoperative venous congestion resulting in partial or total necrosis is still a common problem for these flaps. The aim of the current study is to introduce a new method for reducing the postoperative venous congestion of neural island flap with the results of reconstruction of the soft tissue defects of foot and ankle. This method was used to treat 19 patients with various chronic soft tissue defects of the foot and ankle between 2011 and 2012. We observed that the novel method presented in this report enables effective venous drainage, solving the postoperative venous congestion problem of these flaps.


Cross-Sectional Abdominal Imaging Findings in Patients With COVID-19.
Objective We aimed to review and analyze cross-sectional abdominal imaging findings in a cohort of 10 patients who had tested positive for coronavirus disease 2019 (COVID-19). Methods This retrospective study conducted from April 1, 2020, to May 13, 2020, involved two institutions that comprised a central tertiary academic institution and multiple smaller community hospitals. We reviewed and examined cross-sectional imaging studies of patients who tested positive for COVID-19 either during the emergency room (ER) visit or hospital admission. Salient imaging findings and medical records were reviewed. Results A total of 10 COVID-19-positive patients (seven males and three females) of ages ranging from 21-75 years underwent cross-sectional abdominopelvic imaging. Nine of the 10 patients demonstrated typical lung base findings associated with COVID-19 on both CT and MRI. Twelve CT abdominopelvic examinations, one MRI abdomen, and one right upper quadrant ultrasound (RUQ US) were performed, with three patients undergoing two CT scans during the course of hospitalization. Gastric and bowel wall abnormalities were found on 25% (n=3/12) of abdominal CT scans. Acute interstitial pancreatitis and acute cholecystitis were both found on one CT exam. The remaining (n=7/12, 58%) CT studies demonstrated no acute intraabdominal pathology with incidental findings including fatty liver disease, cirrhosis, and splenomegaly. Conclusion A spectrum of abdominal imaging findings ranging from colitis to pancreatitis may be correlated with COVID-19 infection, even though the majority of our patients with gastrointestinal (GI) symptoms did not have identifiable GI pathology on imaging.


Single nucleotide polymorphism in gene encoding transcription factor Prep1 is associated with HIV-1-associated dementia.
Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders.


Understanding structural malleability of the SARS-CoV-2 proteins and relation to the comorbidities.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease (COVID-19), is a part of the $\beta $-Coronaviridae family. The virus contains five major protein classes viz., four structural proteins [nucleocapsid (N), membrane (M), envelop (E) and spike glycoprotein (S)] and replicase polyproteins (R), synthesized as two polyproteins (ORF1a and ORF1ab). Due to the severity of the pandemic, most of the SARS-CoV-2-related research are focused on finding therapeutic solutions. However, studies on the sequences and structure space throughout the evolutionary time frame of viral proteins are limited. Besides, the structural malleability of viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins. This dysfunctionality may lead to comorbidities during the infection and may continue at the post-infection stage. In this regard, we conduct the evolutionary sequence-structure analysis of the viral proteins to evaluate their malleability. Subsequently, intrinsic disorder propensities of these viral proteins have been studied to confirm that the short intrinsically disordered regions play an important role in enhancing the likelihood of the host proteins interacting with the viral proteins. These interactions may result in molecular dysfunctionality, finally leading to different diseases. Based on the host cell proteins, the diseases are divided in two distinct classes: (i) proteins, directly associated with the set of diseases while showing similar activities, and (ii) cytokine storm-mediated pro-inflammation (e.g. acute respiratory distress syndrome, malignancies) and neuroinflammation (e.g. neurodegenerative and neuropsychiatric diseases). Finally, the study unveils that males and postmenopausal females can be more vulnerable to SARS-CoV-2 infection due to the androgen-mediated protein transmembrane serine protease 2.


An approach to the problem of false negatives in gynecologic cytologic screening.
A system of quality control for gynecologic cytologic screening designed to minimize the problem of false-negative cytologic reports is proposed. The system involves the harvesting of "quality control" smears, at the time of colposcopic examination, from patients referred to colposcopy because of previous abnormal smears that had been interpreted as representing dysplasia or neoplasia. These quality control smears are then submitted to the cytology laboratory, indistinguishable from bona fide cases, among the routine smears. This appears to be a more effective means of quality control than the current standard system used in the United States, which involves cytology laboratories routinely rescreening 10% of the slides reported out as "negative".


Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature.
Cholesteryl ester storage disease (CESD) is a rare genetic disease. Its symptoms and severity are highly variable. CESD is a systemic disease that can lead to the accumulation of fat and inflammation in the liver, as well as gastrointestinal and cardiovascular disease. The majority of patients require liver transplantation due to decompensated cirrhosis. Enzyme replacement therapy has been approved based on a randomized trial. Our study aims to clinically and genetically evaluate two siblings with CESD who underwent liver transplantation, as well as their first-degree family members. The siblings were compound heterozygous for the missense variant in LIPA exon 8, c.894G>A, (p.Gln298Gln) and a single base pair deletion, c.482del (p.Asn161Ilefs*19). Analyses of single nucleotide polymorphisms showed variants with an increased risk of fatty liver disease and fibrosis for both patients. Clinically, both patients show signs of recurrence of CESD in the liver after transplantation and additional gastrointestinal and cardiovascular signs of CESD. Three family members who were LIPA heterozygous had a lysosomal acid lipase activity below the reference value. One of these carriers, a seven-year-old boy, was found to have severe dyslipidemia and was subsequently treated with statins. Our study underlines that CESD is a multi-organ disease, the progression of which may occur post-liver transplantation. Our findings underline the need for monitoring of complications and assessment of possible further treatment.


Otolaryngic manifestations in children presenting with apparent life-threatening events.
Apparent life-threatening event (ALTE) is a term used to characterize an event of unknown cause after an infant is found limp, cyanotic, bradycardic, and/or requiring resuscitation. Like sudden infant death syndrome (SIDS), ALTE is a general term used until a precise diagnosis can be established. The relationship between ALTE and SIDS has not been clearly defined, although 7 to 15 percent of children with ALTE die of SIDS. If children with ALTE are at greater risk for SIDS, morbidity and mortality may be prevented if the underlying pathology can be identified and corrected or closely monitored. The otolaryngologist is being consulted more frequently to evaluate children who have been through an ALTE to help elucidate any underlying pathology that may have caused the near-death experience. This retrospective chart review reports the evaluation of 30 infants with ALTE requiring consultation by the Division of Pediatric Otolaryngology at the Children's Memorial Hospital in Chicago during a 3-year period. We reviewed the literature and here compare our findings with current animal models. Of the 30 children evaluated, 53% had gastroesophageal reflux, 40% had laryngeal abnormalities, 13% had tracheal abnormalities, and 10% had pharyngeal abnormalities. Thirteen percent of the children had nonotolaryngic anomalies identified during evaluation. Surgical intervention was required in 10 patients and medical treatment was used in 18. When evaluating a child with ALTE, a complete history and physical examination, evaluation for gastroesophageal reflux, assessment for upper airway obstruction by radiographs and endoscopy, and a multidisciplinary approach are recommended.


Active travel and physical activity across the school transition: the PEACH project.
Physical activity in youth decreases with age, with the transition from primary to secondary school being a key period for change. Active travel to school has been associated with higher physical activity in youth compared with those who travel by car. This study investigated whether change in travel mode to/from school was associated with change in physical activity among young people transitioning from primary to secondary school. One thousand three hundred and seven final year UK primary school children (11.0 ± 0.4 yr) were recruited, of whom 953 (72.9%) were followed-up 1 yr later in their first year of secondary school. Physical activity was measured by accelerometer, and travel mode to/from school was self-reported. Change in moderate-to-vigorous physical activity (MVPA) associated with change in travel mode between primary and secondary school was measured in 500 children who provided valid accelerometer data and used a consistent travel mode to/from school at each time point. Total MVPA was slightly higher in secondary school than primary school (60.6 ± 21.6 vs. 63.1 ± 23.6 min, respectively, P = 0.017). Daily MVPA increased by 11.4% in children who walked both to primary and secondary school (63.4 ± 22.0 vs. 70.6 ± 23.0 min, P < 0.001). In those who changed from walking to car travel, MVPA decreased by 15.5% (62.5 ± 22.0 vs. 52.8 ± 21.5 min, P = 0.003), whereas adoption of bus travel was associated with smaller reductions. A change from car travel to walking was associated with 16.1% more daily MVPA (50.1 ± 14.3 vs. 58.2 ± 20.6 min, P = 0.038). Change from active to passive transportation to school may contribute to the decline in physical activity seen between primary and secondary school.


Seal body condition and atmospheric circulation patterns influence polar bear body condition, recruitment, and feeding ecology in the Chukchi Sea.
Polar bears (Ursus maritimus) are experiencing loss of sea ice habitats used to access their marine mammal prey. Simultaneously, ocean warming is changing ecosystems that support marine mammal populations. The interactive effects of sea ice and prey are not well understood yet may explain spatial-temporal variation in the response of polar bears to sea ice loss. Here, we examined the potential combined effects of sea ice, seal body condition, and atmospheric circulation patterns on the body condition, recruitment, diet, and feeding probability of 469 polar bears captured in the Chukchi Sea, 2008-2017. The body condition of ringed seals (Pusa hispida), the primary prey of females and subadults, was related to dietary proportions of ringed seal, feeding probability, and the body condition of females and cubs. In contrast, adult males consumed more bearded seals (Erignathus barbatus) and exhibited better condition when bearded seal body condition was higher. The litter size, number of yearlings per adult female, and the condition of dependent young were higher following winters characterized by low Arctic Oscillation conditions, consistent with a growing number of studies. Body condition, recruitment, and feeding probability were either not associated or negatively associated with sea ice conditions, suggesting that, unlike some subpopulations, Chukchi Sea bears are not currently limited by sea ice availability. However, spring sea ice cover declined 2% per year during our study reaching levels not previously observed in the satellite record and resulting in the loss of polar bear hunting and seal pupping habitat. Our study suggests that the status of ice seal populations is likely an important factor that can either compound or mitigate the response of polar bears to sea ice loss over the short term. In the long term, neither polar bears nor their prey are likely robust to limitless loss of their sea ice habitat.


Bilateral vidian nerve schwannomas associated with facial palsy. Case report and review of the literature.
Intracranial schwannomas are relatively common benign tumors arising from Schwann cells. Among the cranial nerves, the vestibular division of the vestibulocochlear nerve is the site most commonly affected by these lesions, followed by the trigeminal nerve. The authors report a case of bilateral schwannomas arising from both of the pterygoid canals. A 13-year-old girl presented with intermittent headaches and left-sided facial palsy. Preoperative computerized tomography scans and magnetic resonance images revealed nonenhancing round masses within the bilateral vidian canals, bone erosion, and sclerosis. The transnasal transseptal transsphenoidal approach was used to remove the masses. Postoperatively, the patient recovered uneventfully. On histopathological examination, the masses were confirmed as schwannomas. The clinical presentation and probable histogenesis of schwannomas arising in this location are discussed together with a review of the literature.


Role Stress and Psychological Distress Among Chinese Nurses During the COVID-19 Pandemic: A Moderated Mediation Model of Social Support and Burnout.
Nurses are at high risk of psychological distress including stress, depression, and anxiety due to low personnel density and high work demand. Despite mounting evidence showing that role stress is a risk factor for nurses' psychological distress, the mediating and moderating mechanisms underlying this relationship are less known. This study tests the mediation effect of burnout in the association between role stress and psychological distress, and whether this mediation is moderated by social support. A sample of 623 Chinese nurses were recruited from all hepatological surgery departments in Hunan Province and filled out an online questionnaire to collect data on socio-demographics, role stress, burnout, psychological distress, and social support. Mediation and moderation analyses were carried out in SPSS macro-PROCESS. Burnout partially mediated the positive association between role stress and psychological distress. Social support moderated the indirect effect of role stress on psychological distress via burnout, with the effect being stronger for nurses with low social support than those with high social support. These findings demonstrated how role stress contributed to nurses' psychological distress both directly and indirectly through burnout, and how this indirect effect was moderated by social support. The results provide important practical implications for future prevention and intervention programs to improve nurses' mental health from multiple aspects such as decreasing role stress and burnout while increasing social support.


Differential Susceptibility of Retinal Neurons to the Loss of Mitochondrial Biogenesis Factor Nrf1.
The retina, the accessible part of the central nervous system, has served as a model system to study the relationship between energy utilization and metabolite supply. When the metabolite supply cannot match the energy demand, retinal neurons are at risk of death. As the powerhouse of eukaryotic cells, mitochondria play a pivotal role in generating ATP, produce precursors for macromolecules, maintain the redox homeostasis, and function as waste management centers for various types of metabolic intermediates. Mitochondrial dysfunction has been implicated in the pathologies of a number of degenerative retinal diseases. It is well known that photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and susceptibility to oxidative stress. However, it is unclear how defective mitochondria affect other retinal neurons. Nuclear respiratory factor 1 (Nrf1) is the major transcriptional regulator of mitochondrial biogenesis, and loss of Nrf1 leads to defective mitochondria biogenesis and eventually cell death. Here, we investigated how different retinal neurons respond to the loss of Nrf1. We provide in vivo evidence that the disruption of Nrf1-mediated mitochondrial biogenesis results in a slow, progressive degeneration of all retinal cell types examined, although they present different sensitivity to the deletion of Nrf1, which implicates differential energy demand and utilization, as well as tolerance to mitochondria defects in different neuronal cells. Furthermore, transcriptome analysis on rod-specific Nrf1 deletion uncovered a previously unknown role of Nrf1 in maintaining genome stability.


Microsporidial infections in immunodeficient and immunocompetent patients.
Microsporidia are obligate, intracellular, spore-forming protozoal parasites. Their host range is extensive and includes most invertebrates and all classes of vertebrates. Five microsporidial genera (Enterocytozoon, Encephalitozoon, Septata, Pleistophora, and Nosema) and unclassified microsporidia have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. The majority of microsporidial infections in persons infected with human immunodeficiency virus (HIV) are attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Four cases of microsporidial infection among persons not infected with HIV who had documented or presumed cellular immunodeficiency and four cases of corneal stroma infection due to microsporidia in immunocompetent patients have been described. Furthermore, the first case of traveler's diarrhea due to E. bieneusi in an immunocompetent and otherwise healthy patient is reported in this issue. The sources of human microsporidial infections and modes of transmission are unknown.


mRNA Processing Factor CstF-50 and Ubiquitin Escort Factor p97 Are BRCA1/BARD1 Cofactors Involved in Chromatin Remodeling during the DNA Damage Response.
The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. In this study, we provide evidence of the roles of the polyadenylation factor cleavage stimulation factor 50 (CstF-50) and the ubiquitin (Ub) escort factor p97 as cofactors of BRCA1/BARD1 E3 Ub ligase, facilitating chromatin remodeling during the DNA damage response (DDR). CstF-50 and p97 formed complexes with BRCA1/BARD1, Ub, and some BRCA1/BARD1 substrates, such as RNA polymerase (RNAP) II and histones. Furthermore, CstF-50 and p97 had an additive effect on the activation of the ubiquitination of these BRCA1/BARD1 substrates during DDR. Importantly, as a result of these functional interactions, BRCA1/BARD1/CstF-50/p97 had a specific effect on the chromatin structure of genes that were differentially expressed. This study provides new insights into the roles of RNA processing, BRCA1/BARD1, the Ub pathway, and chromatin structure during DDR.


Recording and Reconstructing Three-Dimensional Images of Computer-Generated Subjects by Lippmann ntegral Photography.
Lippmann's method of integral photography is used to form a permanent record of three-dimensional subject information generated by means of a computer. The computer generates the information contour-by-contour. These contours are then visually displayed and sequentially recorded by multiple exposure of a photographic plate behind a fly's-eye lens. Illumination of an integral photograph normally leads to a three-dimensional image which is pseudoscopic and a second recording is required to obtain the orthoscopic image. The present method of sequentially recording contours allows formation of an orthoscopic image from a single recording process.


From Ambivalence to Revitalization: Negotiating Cardiovascular Health Behaviors Related to Environmental and Historical Trauma in a Northwest American Indian Community.
Cardiovascular disease is the number one cause of death among American Indians and Alaska Natives (AI/AN). Utilizing narratives from members of a Pacific Northwest tribe, this paper explores perceptions about behaviors affecting cardiovascular health through tribal members' lived experiences related to place-based environmental historical trauma. Findings from narrative analysis indicate that ambivalence is an effect of historical trauma and complicates the adoption of protective cardiovascular health behaviors. Tribal narratives indicate a path to overcome this ambivalence stemming from historical environmental trauma through revitalization, adaptation, and re-integration of traditional cultural practices to contemporary contexts. By creating their own health promotion response, one that is not imposed or colonizing, tribal members are re-generating cultural practices and health behaviors associated with lowered risks of cardiovascular disease.


Sulfated Galactofucans: An Outstanding Class of Fucoidans with Promising Bioactivities.
Fucoidans encompass versatile and heterogeneous sulfated biopolysaccharides of marine origin, specifically brown algae and marine invertebrates. Their chemistry and bioactivities have been extensively investigated in the last few decades. The reported studies revealed diverse chemical skeletons in which l-fucose is the main sugar monomer. However, other sugars, i.e., galactose, mannose, etc., have been identified to be interspersed, forming several heteropolymers, including galactofucans/fucogalactans (G-fucoidans). Particularly, sulfated galactofucans are associated with rich chemistry contributing to more promising bioactivities than fucans and other marine polysaccharides. The previous reports in the last 20 years showed that G-fucoidans derived from Undaria pinnatifida were the most studied; 21 bioactivities were investigated, especially antitumor and antiviral activities, and unique biomedical applications compared to other marine polysaccharides were demonstrated. Hence, the current article specifically reviews the biogenic sources, chemistry, and outstanding bioactivities of G-fucoidans providing the opportunity to discover novel drug candidates.


Amount of Televised Alcohol Advertising Exposure and the Quantity of Alcohol Consumed by Youth.
Although studies demonstrate that exposure to brand-specific alcohol advertising is associated with an increased likelihood of youth consuming particular brands, the relationship between quantity of brand-specific advertising exposure and quantity of brand-specific consumption has not been firmly established. Using the Alcohol Brand Research Among Underage Drinkers (ABRAND) national sample of 1,031 young drinkers (ages 13-20), this study examined the relationship between their aggregated past-year exposure to advertising (in adstock units, a measure based on gross rating points) for 61 alcohol brands that advertised on the 20 most popular nonsports television programs viewed by underage youth and their aggregated total consumption of those same brands during the past 30 days. Predictive models adjusted for other media exposure, predictors of youth's alcohol consumption, and the consumption of brands not advertised on the 20 shows. For the fully adjusted models, each 100 adstock unit increase in exposure (about 1 SD) was associated with an increase of 5.9 drinks (95% CI [0.9, 11.0 drinks]) consumed during the past 30 days among those with less than 300 units of advertising exposure, and an increase of 55.7 drinks (95% CI [13.9, 97.4 drinks]) among those with 300 or more adstock units of exposure. Among underage youth, the quantity of brand-specific advertising exposure is positively associated with the total quantity of consumption of those advertised brands, even after controlling for the consumption of non-advertised brands. Future research should examine exposure-consumption relationships longitudinally and in other media.


Characterization of A11 neurons projecting to the spinal cord of mice.
The hypothalamic A11 region has been identified in several species including rats, mice, cats, monkeys, zebrafish, and humans as the primary source of descending dopamine (DA) to the spinal cord. It has been implicated in the control of pain, modulation of the spinal locomotor network, restless leg syndrome, and cataplexy, yet the A11 cell group remains an understudied dopaminergic (DAergic) nucleus within the brain. It is unclear whether A11 neurons in the mouse contain the full complement of enzymes consistent with traditional DA neuronal phenotypes. Given the abundance of mouse genetic models and tools available to interrogate specific neural circuits and behavior, it is critical first to fully understand the phenotype of A11 cells. We provide evidence that, in addition to tyrosine hydroxylase (TH) that synthesizes L-DOPA, neurons within the A11 region of the mouse contain aromatic L-amino acid decarboxylase (AADC), the enzyme that converts L-DOPA to dopamine. Furthermore, we show that the A11 neurons contain vesicular monoamine transporter 2 (VMAT2), which is necessary for packaging DA into vesicles. On the contrary, A11 neurons in the mouse lack the dopamine transporter (DAT). In conclusion, our data suggest that A11 neurons are DAergic. The lack of DAT, and therefore the lack of a DA reuptake mechanism, points to a longer time of action compared to typical DA neurons.


SARS-CoV-2 infection in children with rheumatic disease: Experience of a tertiary referral center.
In this study, we present our clinical severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) experience in patients with childhood rheumatic disease during novel coronavirus-2019 (COVID-19) pandemic. A total of 87 patients (50 males, 37 females; median age: 12 years; range, 6.6 to 16 years) suspected of having COVID-19 at our pediatric rheumatology clinic between March 11th and October 15th 2020 were retrospectively analyzed. Demographic and clinical features, treatments, laboratory results, imaging findings, and clinical outcomes of the patients diagnosed with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) were retrieved from the medical records. The diagnosis of SARS-CoV-2 infection was made based on the reverse transcriptase-polymerase chain reaction test. The most common rheumatic diseases were juvenile idiopathic arthritis and familial Mediterranean fever (35.6% and 34.5%, respectively). Twenty-six of these patients were treated with biological disease-modifying anti-rheumatic drugs. SARS-CoV-2 infection was tested as positive in 84 (96.5%) patients. Also, 51 (58.6%) patients had an epidemiological contact to a person with COVID-19. Eighteen patients met the clinical criteria and diagnosed with MIS-C. The COVID-19 outbreak also caused exacerbation of systemic disease in 56 children due to medication cessation, postponed drug switch, or recurrent viral infection. Children with rheumatic disease do not appear to present a higher risk of severe COVID-19. The immunosuppressive treatments can be adjusted in case of infection; otherwise, it is not recommended to interrupt the treatments. Physicians should be cautious about the hyperinflammatory syndrome associated with COVID-19 in rheumatic children, which may be severe in this group of patients and may be confused with primary diseases.


IL-1 receptor-associated kinase modulates host responsiveness to endotoxin.
Endotoxin triggers many of the inflammatory, hemodynamic, and hematological derangements of Gram-negative septic shock. Recent genetic studies in mice have identified the Toll-like receptor 4 as the transmembrane endotoxin signal transducer. The IL-1 intracellular signaling pathway has been implicated in Toll-like receptor signal transduction. LPS-induced activation of the IL-1 receptor-associated kinase (IRAK), and the influence of IRAK on intracellular signaling and cellular responses to endotoxin has not been explored in relevant innate immune cells. We demonstrate that LPS activates IRAK in murine macrophages. IRAK-deficient macrophages, in contrast, are resistant to LPS. Deletion of IRAK disrupts several endotoxin-triggered signaling cascades. Furthermore, macrophages lacking IRAK exhibit impaired LPS-stimulated TNF-alpha production, and IRAK-deficient mice withstand the lethal effects of LPS. These findings, coupled with the critical role for IRAK in IL-1 and IL-18 signal transduction, demonstrate the importance of this kinase and the IL-1/Toll signaling cassette in sensing and responding to Gram-negative infection.


Global Geriatric Assessment and In-Hospital Bleeding Risk in Elderly Patients with Acute Coronary Syndromes: Insights from the LONGEVO-SCA Registry.
Bleeding risk scores have shown a limited predictive ability in elderly patients with acute coronary syndromes (ACS). No study explored the role of a comprehensive geriatric assessment to predict in-hospital bleeding in this clinical setting. The prospective multicentre LONGEVO-SCA registry included 532 unselected patients with non-ST segment elevation ACS (NSTEACS) aged 80 years or older. Comorbidity (Charlson index), frailty (FRAIL scale), disability (Barthel index and Lawton-Brody index), cognitive status (Pfeiffer test) and nutritional risk (mini nutritional assessment-short form test) were assessed during hospitalization. CRUSADE score was prospectively calculated for each patient. In-hospital major bleeding was defined by the CRUSADE classification. The association between geriatric syndromes and in-hospital major bleeding was assessed by logistic regression method and the area under the receiver operating characteristic curves (AUC). Mean age was 84.3 years (SD 4.1), 61.7% male. Most patients had increased troponin levels (84%). Mean CRUSADE bleeding score was 41 (SD 13). A total of 416 patients (78%) underwent an invasive strategy, and major bleeding was observed in 37 cases (7%). The ability of the CRUSADE score for predicting major bleeding was modest (AUC 0.64). From all aging-related variables, only comorbidity (Charlson index) was independently associated with major bleeding (per point, odds ratio: 1.23, p = 0.021). The addition of comorbidity to CRUSADE score slightly improved the ability for predicting major bleeding (AUC: 0.68). Comorbidity was associated with major bleeding in very elderly patients with NSTEACS. The contribution of frailty, disability or nutritional risk for predicting in-hospital major bleeding was marginal.


Using surface-enhanced Raman spectroscopy and electrochemically driven melting to discriminate Yersinia pestis from Y. pseudotuberculosis based on single nucleotide polymorphisms within unpurified polymerase chain reaction amplicons.
The development of sensors for the detection of pathogen-specific DNA, including relevant species/strain level discrimination, is critical in molecular diagnostics with major impacts in areas such as bioterrorism and food safety. Herein, we use electrochemically driven denaturation assays monitored by surface-enhanced Raman spectroscopy (SERS) to target single nucleotide polymorphisms (SNPs) that distinguish DNA amplicons generated from Yersinia pestis, the causative agent of plague, from the closely related species Y. pseudotuberculosis. Two assays targeting SNPs within the groEL and metH genes of these two species have been successfully designed. Polymerase chain reaction (PCR) was used to produce Texas Red labeled single-stranded DNA (ssDNA) amplicons of 262 and 251 bases for the groEL and metH targets, respectively. These amplicons were used in an unpurified form to hybridize to immobilized probes then subjected to electrochemically driven melting. In all cases electrochemically driven melting was able to discriminate between fully homologous DNA and that containing SNPs. The metH assay was particularly challenging due to the presence of only a single base mismatch in the middle of the 251 base long PCR amplicon. However, manipulation of assay conditions (conducting the electrochemical experiments at 10 °C) resulted in greater discrimination between the complementary and mismatched DNA. Replicate data were collected and analyzed for each duplex on different days, using different batches of PCR product and different sphere segment void (SSV) substrates. Despite the variability introduced by these differences, the assays are shown to be reliable and robust providing a new platform for strain discrimination using unpurified PCR samples.


Tracing our roots: early clinical laboratory scientists and their work--myth and reality.
To describe the 'real' and 'ideal' clinical laboratory scientist according to the perceptions of pathologists, clinical laboratory scientists, and the public during the early years of the profession (1918 to 1942). A survey of literature on the history of clinical laboratory science was conducted. References consulted include various books and professional journals. As early as 1920, young women learned, through career guides, that they were particularly well-suited for performing laboratory work because they possessed a unique set of attributes which were considered to be desirable qualities in a clinical laboratory scientist. In addition, magazine articles published in the popular press in the 1930s and 1940s romanticized laboratory technicians. Although later articles did present a more realistic description of the work of the laboratory technician, they continued to portray the occupation in idealistic terms. Pathologists and laboratory technicians also described the ideal laboratory technician in professional journals, citing those qualities that were essential or especially desirable in a competent laboratory technician. The relationship between the clinical pathologists and the laboratory technician was described as one of mutual interdependence and integration of responsibilities. In reality, pathologists maintained strict supervision and control over the work of laboratory technicians. The 'real' laboratory technician differed markedly from the 'ideal' prototype created by the public, pathologists, and by laboratory technicians, themselves.


Localization of antigenic sites of the S glycoprotein of feline infectious peritonitis virus involved in neutralization and antibody-dependent enhancement.
The S glycoprotein of feline infectious peritonitis virus (FIPV) has been shown to contain the antigenic sites responsible for eliciting both neutralization and antibody-dependent enhancement. To determine the region of S responsible, overlapping DNA fragments spanning the entire S gene were cloned and expressed as fusion proteins by in vitro transcription and translation. Fusion proteins containing relevant epitopes were identified by radioimmunoprecipitation with neutralizing and enhancing FIPV-specific monoclonal antibodies (MAbs). A region spanning residues 509 to 673 reacted with most MAbs tested. Translation in the presence of microsomal membranes did not enhance reactivity, suggesting that glycosylation is not essential for recognition by the MAbs. To localize the antigenic sites further, several MAb-resistant (mar) mutants of FIPV were cloned and sequenced. Amino acid residues that contribute to the neutralizing and enhancing epitopes were localized to two regions, designated A1 and A2, which show partial overlap with the homologous antigenic site A of transmissible gastroenteritis virus. Site A1 contains residues 568 and 591 and is homologous with part of subsite Aa of transmissible gastroenteritis virus. Site A2 contains residues 643, 649, and 656. Double mutations in sites A1 and A2 were found in mar mutants derived from neutralizing and enhancing MAbs 23F4.5 and 18A7.4, while a single mutation in site A2 was found in a mar mutant derived from MAb 24H5.4, which is neutralizing but not enhancing. The data suggest that site A2, which includes residues 643 to 656, is a dominant neutralizing site of FIPV and that sites A1 and A2 may act in concert to induce antibody-dependent enhancement.


Identification of gut microbial species linked with disease variability in a widely used mouse model of colitis.
Experimental mouse models are central to basic biomedical research; however, variability exists across genetically identical mice and mouse facilities making comparisons difficult. Whether specific indigenous gut bacteria drive immunophenotypic variability in mouse models of human disease remains poorly understood. We performed a large-scale experiment using 579 genetically identical laboratory mice from a single animal facility, designed to identify the causes of disease variability in the widely used dextran sulphate sodium mouse model of inflammatory bowel disease. Commonly used treatment endpoint measures-weight loss and intestinal pathology-showed limited correlation and varied across mouse lineages. Analysis of the gut microbiome, coupled with machine learning and targeted anaerobic culturing, identified and isolated two previously undescribed species, Duncaniella muricolitica and Alistipes okayasuensis, and demonstrated that they exert dominant effects in the dextran sulphate sodium model leading to variable treatment endpoint measures. We show that the identified gut microbial species are common, but not ubiquitous, in mouse facilities around the world, and suggest that researchers monitor for these species to provide experimental design opportunities for improved mouse models of human intestinal diseases.


Bidirectional causal control in the dynamics of handstand balance.
The aim of this study was to identify motor control solutions associated with the ability to maintain handstand balance. Using a novel approach, we investigated the dynamical interactions between centre of pressure (CoP) and centre of mass (CoM) motion. A gymnastics cohort was divided into a 'less skilled' group, who held handstands for 4-6 s, and a 'more skilled' group, who held handstands in excess of 10 s. CoP-CoM causality was investigated in anterior-posterior (AP) and medio-lateral (ML) directions, in addition to time-space, time-frequency and Hurst Exponent (H) analyses. Lower AP CoP to CoM causal drive and lower H values (> 0.6) indicated the more skilled gymnasts were less reliant on CoP mechanics to drive CoM motion. More skilled performance demonstrated greater adaptability through use of reactive, as opposed to anticipatory, control strategies. Skilled performers additionally exploited mechanical advantages in ML (e.g. a wider base of support), compared to the less skilled athletes. A multiple regression analysis revealed H and frequency domain measures to be better predictors of handstand balance duration than time-space domain measures. The study findings highlight the advantage of an adaptable motor control system with a directional profile, and provide new insight into the clear, measurable footprint of CoP on the dynamics of CoM.


Efficiency of in vivo labeling of red blood cells with 99mTc.
The effectiveness of three commercial bone scintigraphic agents and freshly made stannous chloride in labeling erythrocytes with 99mTc was compared. Our results indicate that tin pyrophosphate is the agent of choice and that it is most effective when injected at least 15 minutes before the 99mTc-pertechnetate is administered. This technique of labeling red blood cells in vivo could be applied in performing blood pool studies.


Japanese patients with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: In vitro functional analysis of five novel HMGCS2 mutations.
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) deficiency is a metabolic disorder caused by mutations in the HMGCS2 gene. The present study describes the identification of four cases of HMGCS2 deficiency in Japan. Hepatomegaly and severe metabolic acidosis were observed in all cases. Fatty liver was identified in three cases, which suggested the unavailability of fatty acids. All patients presented with a high C2/C0 ratio, suggesting that the fatty acid oxidation pathway was normal during metabolic crisis. Genetic analyses revealed five rare, novel variants (p.G219E, p.M235T, p.V253A, p.S392L and p.R500C) in HMGCS2. To confirm their pathogenicity, a eukaryotic expression system and a bacterial expression system was adopted that was successfully used to obtain affinity-purified HMGCS2 protein with measurable activity. Purified M235T, S392L and R500C proteins did not retain any residual activity, whilst the V253A variant showed some residual enzymatic activity. Judging from the transient expression experiment in 293T cells, the G219E variant appeared to be unstable. In conclusion, the present study identified five novel variants of HMGCS2 that were indicated to be pathogenic in four patients affected by HMGCS2 deficiency.