Chronic survival of calves implanted with the DeBakey ventricular assist device.
The DeBakey ventricular assist device (VAD) is a miniaturized, electromagnetically driven axial flow pump capable of generating in excess of 10 L/min output. The VAD was evaluated in 19 calves during experiments designed to test iterative modifications in the system and to determine the safety of the DeBakey VAD for intermediate to long-term implant. Five of the animals died or were euthanized during the perioperative period (i.e., Days 1-5) due to complications associated with bleeding (n = 3), sudden cardiac arrest (n = 1), or pump occlusion due to a muscle remnant associated with coring (n = 1). The remaining 14 animals survived from 7-145 days. Ten of the 14 animals survived 30 or more days, and 2 animals survived 93 and 145 days before elective euthanasia. Pump function was evaluated in the 14 calves that survived beyond the perioperative period. Pump output at implantation averaged 3 L/min while output at 100 days (n = 2) averaged 4.22 L/min. The electrical current did not change across time during the study, indicating normal operation of the bearings. Pumps consumed less than 10.5 W of power for all support durations. Hemolysis did not occur; the average daily plasma free hemoglobin varied from 2.0 to 8.0 mg/dl. Evaluation of serum biochemical data showed that implantation of the DeBakey VAD in calves with normal hearts did not impair end organ function; BUN, creatinine, and total bilirubin varied minimally within the normal range. The white blood cell count of implanted animals remained within the normal range throughout the study.


Interactions between the Bumblebee Bombus pascuorum and Red Clover (Trifolium pratense) Are Mediated by Plant Genetic Background.
Wildflower mixes are often planted around field margins to provide forage for pollinators. Although seed for these mixtures is often wild-sourced, for species where agricultural cultivars are available, for example red clover (Trifolium pratense), cultivars can also be included. Previous evidence suggests that plant genetic background can have a strong influence on plant-arthropod interactions and therefore the provenance and genetic background of the plants included in wildflower mixes could impact plant-pollinator interactions. We tested the performance of five individual T. pratense cultivars against two commercially available wild-sourced T. pratense populations in terms of their ability to attract potential pollinator species (focusing on bumblebees) and their floral traits using greenhouse and garden experiments. The main bumblebee observed interacting with T. pratense was Bombus pascuorum and we found no difference in the absolute number of B. pascuorum visiting the cultivars or wild populations. However, we found variation among cultivars and between wild populations in their ability to attract bumblebees, which seems to be related to their relative investment in different floral traits. There was a positive relationship between biomass and number of inflorescences produced by the wild populations of T. pratense, which was not apparent for the cultivars. This suggests that artificial selection on the cultivars has changed the G-matrix of correlated traits. We show that agricultural cultivars of T. pratense can be as effective as wild populations at attracting pollinators such as bumblebees, but that the genetic background of both cultivars and wild populations can have a significant impact on the attractiveness of the plant to pollinators. We also show divergence in the correlated traits of T. pratense cultivars and wild populations that could lead to outbreeding depression if the plants interbreed.


Acute toxicity of sodium chloride and potassium chloride to a unionid mussel (Lampsilis siliquoidea) in water exposures.
Freshwater mussels (order Unionoida) are one of the most imperiled groups of animals in the world. However, many ambient water quality criteria and other environmental guideline values do not include data for freshwater mussels, in part because mussel toxicity test methods are comparatively new and data may not have been available when criteria and guidelines were derived. The objectives of the present study were to evaluate the acute toxicity of sodium chloride (NaCl) and potassium chloride (KCl) to larvae (glochidia) and/or juveniles of a unionid mussel (fatmucket, Lampsilis siliquoidea) and to determine the potential influences of water hardness (50, 100, 200, and 300 mg/L as CaCO3 ) and other major ions (Ca, K, SO4 , or HCO3 ) on the acute toxicity of NaCl to the mussels. From the KCl test, the 50% effect concentration (EC50) for fatmucket glochidia was 30 mg K/L, similar to or slightly lower than the EC50s for juvenile fatmucket (37-46 mg K/L) tested previously in our laboratory. From the NaCl tests, the EC50s for glochidia increased from 441 to 1597 mg Cl/L and the EC50s for juvenile mussels increased from 911 to 3092 mg Cl/L with increasing water hardness from 50 to 300 mg/L. Increasing K from 0.4 to 1.9 mg/L, SO4 from 13 to 40 mg/L, or HCO3 from 44 to 200 mg/L in the 50 mg/L hardness water did not substantially change the NaCl EC50s for juvenile mussels, whereas increasing Ca from 9.9 to 42 mg/L increased the EC50s by a factor of 2. The overall results indicate that glochidia were equally or more sensitive to NaCl and KCl compared with juvenile mussels and that the increased water hardness ameliorated the acute toxicity of NaCl to glochidia and juveniles. These responses rank fatmucket among the most acutely sensitive freshwater organisms to NaCl and KCl. Environ Toxicol Chem 2018;37:3041-3049. © 2018 SETAC. This article is a US government work and, as such, is in thepublic domain in the United States of America.


Symposium review: Amino acid uptake by the mammary glands: Where does the control lie?
Milk protein yield responses to changes in the profile of essential amino acids absorbed by the gastrointestinal tract or circulating in blood plasma do not follow the classic limiting amino acid response, in part because of an ability of the mammary glands to modify their blood flow rate and net clearance of amino acids out of plasma. The hypothesis that mammary blood flow is locally regulated to maintain ATP balance accounts for observed changes in flow due to postruminal glucose, insulin, and essential amino acid (EAA) infusions. An additional hypothesis that net mammary uptakes of metabolites from blood are affected by perturbations in their respective arterial concentrations and the rate of mammary blood flow also appears to hold for the energy metabolites glucose, acetate, β-hydroxybutyrate, and fatty acids. However, net EAA uptakes by the mammary glands are poorly predicted by models considering arterial concentrations and blood flow rates only. Evidence points to intramammary protein synthesis and secretion as the determinant of net EAA uptake. The intracellular signaling network anchored by the mechanistic target of rapamycin complex 1 stands as an excellent candidate to explain nutritional effects on milk protein synthesis because it integrates information on physiological and nutritional state to affect protein synthesis and cell metabolism, growth, proliferation, and differentiation in many cell types. In mammary cells in vitro and in vivo, the mechanistic target of rapamycin complex 1, integrated stress response, and glycogen synthase kinase-3 networks that contribute to regulation of initiation of mRNA translation are responsive to acute changes in nutrient supply and EAA profile. However, after several days of postruminal infusion of balanced and imbalanced EAA profiles, these signaling networks do not appear to continue to account for changes in milk protein yields. Gene expression evidence suggests that regulation of components of the unfolded protein response that control biogenesis of the endoplasmic reticulum and differentiation of a secretory phenotype may contribute to effects of nutrition on milk protein yield. Connections between early signaling events and their long-term consequences should be sought.


A transport and retention mechanism for the sustained distal localization of Spn-F-IKKε during Drosophila bristle elongation.
Stable localization of the signaling complex is essential for the robust morphogenesis of polarized cells. Cell elongation involves molecular signaling centers that coordinately regulate intracellular transport and cytoskeletal structures. In Drosophila bristle elongation, the protein kinase IKKε is activated at the distal tip of the growing bristle and regulates the shuttling movement of recycling endosomes and cytoskeletal organization. However, how the distal tip localization of IKKε is established and maintained during bristle elongation is unknown. Here, we demonstrate that IKKε distal tip localization is regulated by Spindle-F (Spn-F), which is stably retained at the distal tip and functions as an adaptor linking IKKε to cytoplasmic dynein. We found that Javelin-like (Jvl) is a key regulator of Spn-F retention. In jvl mutant bristles, IKKε and Spn-F initially localize to the distal tip but fail to be retained there. In S2 cells, particles that stain positively for Jvl or Spn-F move in a microtubule-dependent manner, whereas Jvl and Spn-F double-positive particles are immobile, indicating that Jvl and Spn-F are transported separately and, upon forming a complex, immobilize each other. These results suggest that polarized transport and selective retention regulate the distal tip localization of the Spn-F-IKKε complex during bristle cell elongation.


Flavin adenine dinucleotide rescues the phenotype of frataxin deficiency.
Friedreich ataxia is a neurodegenerative disease caused by the lack of frataxin, a mitochondrial protein. We previously demonstrated that frataxin interacts with complex II subunits of the electronic transport chain (ETC) and putative electronic transfer flavoproteins, suggesting that frataxin could participate in the oxidative phosphorylation. Here we have investigated the effect of riboflavin and its cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) in Saccharomyces cerevisiae and Caenorhabditis elegans models of frataxin deficiency. We used a S. cerevisiae strain deleted for the yfh1 gene obtained by homologous recombination and we assessed growth in fermentable and non-fermentable cultures supplemented with either riboflavin or its derivates. Experiments with C. elegans were performed in transient knock-down worms (frh-1[RNAi]) generated by microinjection of dsRNA frh-1 into the gonads of young worms. We observed that FAD rescues the phenotype of both defective organisms. We show that cell growth and enzymatic activities of the ETC complexes and ATP production of yfh1Delta cells were improved by FAD supplementation. Moreover, FAD also improved lifespan and other physiological parameters in the C. elegans knock-down model for frataxin. We propose that rescue of frataxin deficiency by FAD supplementation could be explained by an improvement in mitochondrial respiration. We suggest that riboflavin may be useful in the treatment of Friedreich ataxia.


Patient isolation for infection control and patient experience.
Hospitalized patients placed in isolation due to a carrier state or infection with resistant or highly communicable organisms report higher rates of anxiety and loneliness and have fewer physician encounters, room entries, and vital sign records. We hypothesized that isolation status might adversely impact patient experience as reported through Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, particularly regarding communication. Retrospective analysis of HCAHPS survey results over 5 years. A 1,165-bed, tertiary-care, academic medical center. Patients on any type of isolation for at least 50% of their stay were the exposure group. Those never in isolation served as controls. Multivariable logistic regression, adjusting for age, race, gender, payer, severity of illness, length of stay and clinical service were used to examine associations between isolation status and "top-box" experience scores. Dose response to increasing percentage of days in isolation was also analyzed. Patients in isolation reported worse experience, primarily with staff responsiveness (help toileting 63% vs 51%; adjusted odds ratio [aOR], 0.77; P = .0009) and overall care (rate hospital 80% vs 73%; aOR, 0.78; P < .0001), but they reported similar experience in other domains. No dose-response effect was observed. Isolated patients do not report adverse experience for most aspects of provider communication regarded to be among the most important elements for safety and quality of care. However, patients in isolation had worse experiences with staff responsiveness for time-sensitive needs. The absence of a dose-response effect suggests that isolation status may be a marker for other factors, such as illness severity. Regardless, hospitals should emphasize timely staff response for this population.


LA-ICP-MS for Pu source identification at Mayak PA, the Urals, Russia.
Information on Pu in environmental samples is traditionally based on the determination of the (240+239)Pu activity via Alpha Spectrometry (AS). A large number of alpha spectrometry sources (planchettes) containing radiochemically separated Pu are therefore stored worldwide and are available for further analyses. These archive samples represent a resource from which valuable information on isotopic composition of alpha emitters including Pu can be obtained. The relative abundances of Pu isotopes can be used to trace specific Pu sources and characterize the relative contributions of different Pu sources in a sample. Thus, in addition to the total (239+240)Pu activity, determination of the (240)Pu/(239)Pu ratio can provide valuable information on the nature of the Pu emitting sources. The Pu isotopic ratios can be determined by mass spectrometry techniques such as Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICPMS) or Accelerator Mass Spectrometry (AMS) that require dissolution and complete destruction of the material deposited on the planchettes. In this study Laser Ablation (LA)-quadrupole-ICP-MS has been employed for the analysis of (239)Pu/(240)Pu ratios from alpha-planchettes prepared from samples originating from the Mayak PA nuclear facility, Russia. The results are compared with data from AMS and show that the (240)Pu/(239)Pu ratios obtained by LA-ICP-MS can be utilized to distinguish weapons-grade Pu from civil reprocessing sources. Moreover, isotope ratio mapping can also be performed across the planchettes, allowing e.g. the visualization of possible inhomogeneities in the Pu-isotope distribution on their surface. Thus, this solid sample technique can be applied to extract additional information from existing archives of samples.


Analysis of COVID-19 Vaccine Type and Adverse Effects Following Vaccination.
Little is known about the factors associated with COVID-19 vaccine adverse effects in a real-world population. To evaluate factors potentially associated with participant-reported adverse effects after COVID-19 vaccination. The COVID-19 Citizen Science Study, an online cohort study, includes adults aged 18 years and older with a smartphone or internet access. Participants complete daily, weekly, and monthly surveys on health and COVID-19-related events. This analysis includes participants who provided consent between March 26, 2020, and May 19, 2021, and received at least 1 COVID-19 vaccine dose. Participant-reported COVID-19 vaccination. Participant-reported adverse effects and adverse effect severity. Candidate factors in multivariable logistic regression models included age, sex, race, ethnicity, subjective social status, prior COVID-19 infection, medical conditions, substance use, vaccine dose, and vaccine brand. The 19 586 participants had a median (IQR) age of 54 (38-66) years, and 13 420 (68.8%) were women. Allergic reaction or anaphylaxis was reported in 26 of 8680 participants (0.3%) after 1 dose of the BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccine, 27 of 11 141 (0.2%) after 2 doses of the BNT162b2 or mRNA-1273 vaccine or 1 dose of the JNJ-78436735 (Johnson & Johnson) vaccine. The strongest factors associated with adverse effects were vaccine dose (2 doses of BNT162b2 or mRNA-1273 or 1 dose of JNJ-78436735 vs 1 dose of BNT162b2 or mRNA-1273; odds ratio [OR], 3.10; 95% CI, 2.89-3.34; P < .001), vaccine brand (mRNA-1273 vs BNT162b2, OR, 2.00; 95% CI, 1.86-2.15; P < .001; JNJ-78436735 vs BNT162b2: OR, 0.64; 95% CI, 0.52-0.79; P < .001), age (per 10 years: OR, 0.74; 95% CI, 0.72-0.76; P < .001), female sex (OR, 1.65; 95% CI, 1.53-1.78; P < .001), and having had COVID-19 before vaccination (OR, 2.17; 95% CI, 1.77-2.66; P < .001). In this real-world cohort, serious COVID-19 vaccine adverse effects were rare and comparisons across brands could be made, revealing that full vaccination dose, vaccine brand, younger age, female sex, and having had COVID-19 before vaccination were associated with greater odds of adverse effects. Large digital cohort studies may provide a mechanism for independent postmarket surveillance of drugs and devices.


In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain.
The capacity of non-pathogenic enteric bacteria to induce a pro-inflammatory response is under debate in terms of its effect on the symbiosis between the mammalian host and its commensal gut microflora. Activation of NF-kappaB and induction of interleukin-8 (IL-8) and CCL-20 by the commensal Escherichia coli strain MG1655 were first studied in vitro in the human intestinal epithelial cell (IECs) lines HT29-19A and Caco-2, transfected or not with plasmids encoding dominant negative Toll-like receptor (TLR) 5 and myeloid differentiation factor-88 (MyD88) adaptor protein. The response of enterocytes in situ was then assessed using murine ileal biopsies mounted in Ussing chambers. Commensal E. coli induced NF-kappaB DNA binding, NF-kappaB transcriptional activity, CCL-20 expression, and IL-8 secretion in the human IEC lines. E. coli MG1655 flagellin was necessary and sufficient to trigger this pro-inflammatory pathway via its interaction with TLR5 and the subsequent recruitment of the adaptor protein MyD88. Following epithelial cell polarization, signaling could be induced by live E. coli and flagellin on the apical side of HT29-19A. The in vivo relevance of our findings was confirmed, because immunohistochemical staining of murine ileum demonstrated expression of TLR5 in the apical part of enterocytes in situ. Furthermore, flagellin added on the mucosal side of murine ileal biopsies mounted in Ussing chambers induced a basolateral production of KC, a functional murine homolog of human IL-8. These findings provide strong evidence that flagellin released by flagellated commensal bacteria in the intestinal lumen can induce a pro-inflammatory response in enterocytes in vivo.


Characterization of ultrafine particulate matter from traditional and improved biomass cookstoves.
Biomass combustion in cookstoves has a substantial impact on human health, affects CO2 levels in the atmosphere, and black carbon (BC) and organic carbon (OC) affect the earth's radiative balance. Various initiatives propose to replace traditional fires with "improved" (nontraditional) cookstoves to offset negative local and global effects. In this laboratory study, we compared the size, composition, and morphology of ultrafine particulate emissions from a "three-stone" traditional fire to those from two improved stove designs (one "rocket", one "gasifier"). Measurement tools included a scanning mobility particle sizer, PTFE and quartz filter samples, and transmission electron microscopy. In the improved stoves, particulate mass (PM) emissions factors were much lower although median particle size was also lower: 35 and 24 nm for the rocket and gasifier, respectively, vs 61 nm for the three-stone fire. Particles from improved stoves formed clearly defined chain agglomerates and independent spheres with little evidence of volatile matter and had a higher proportion of BC to total PM, although overall BC emissions factors were fairly uniform. The 3-fold increase in quantities of sub-30 nm particles from improved cookstoves warrants further consideration by health scientists, with due consideration to the higher combustion efficiencies of improved cookstoves.


TRIM37 promotes cell invasion and metastasis by regulating SIP1-mediated epithelial-mesenchymal transition in gastric cancer.
Tripartite motif containing 37 (TRIM37) has been demonstrated to function importantly during the progression of various cancers. However, the role of TRIM37 in gastric cancer (GC) remains elusive. TRIM37 mRNA and protein expressions were determined by qRT-PCR, Western blot, and immunohistochemical staining in GC specimens. The effects of TRIM37 on GC cells behavior were evaluated by transwell assays in vitro and metastasis assay in vivo, respectively. Besides, qRT-PCR, Western blot, and immunofluorescence staining were employed to detect the expressions of TRIM37 and epithelial-mesenchymal transition (EMT)-related markers. The present study revealed that TRIM37 mRNA or protein expression was significantly increased in GC tissues compared with that in paracancerous control tissues, and its aberrant overexpression was closely associated with clinical metastasis and poor prognosis in patients with GC. TRIM37 knockdown significantly suppressed GC cells migration and invasion in vitro, as well as metastasis in vivo. Inversely, TRIM37 overexpression exerted the opposite effects. Mechanistic studies suggested that SIP1-mediated EMT might be responsible for TRIM37-facilitated GC cells migration and invasion. Our findings revealed that high TRIM37 expression was associated with clinical metastasis and poor survival in patients with GC. TRIM37 promoted GC cells migration and invasion via EMT, mediated by the transcription factor SIP1, thus providing a candidate target for GC treatment.


Cardiovascular effects of serotonin.
The major target for circulating serotonin (released from aggregating platelets) appears to be the blood vessel wall (although little evidence is available), suggesting a role for the monoamine in controlling cardiac function. In cerebral blood vessels, serotonergic neurons are present, implying a potential serotonergic neurogenic control. Serotonin causes contraction of most large arteries and veins; it also causes contraction of venules. This is due mainly to direct activation of vascular smooth muscle, although amplification of the response to other endogenous vasoconstrictors (e.g., angiotensin II and norepinephrine) as well as facilitated release of norepinephrine may contribute. In peripheral blood vessels, the receptors mediating the contractions evoked by serotonin belong mainly to the 5-HT2-serotonergic subtype; in the coronary and cerebral arteries, this need not be the case. Vasodilator responses to serotonin are seen mainly at the arteriolar level, but they can also be observed in larger blood vessels. They can be caused by the release of other endogenous vasodilators (e.g., vasoactive intestinal polypeptide), direct relaxation of vascular smooth muscle, inhibition of adrenergic neurotransmission, or production of endothelium-derived relaxing factor(s). The dilator responses to serotonin are mediated by receptors with characteristics similar to 5-HT1-serotonergic binding sites. Aggregating platelets release enough serotonin to evoke both constrictor and dilator responses. The absence of endothelium may change the primary response to aggregating platelets from relaxation to contraction. The responsiveness of the blood vessel wall to serotonin can be augmented acutely by local hypoxia or by cooling. It is exaggerated in blood vessels taken from hypertensive or atherosclerotic animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Current and potential support for chronic disease management in the United States: the perspective of family and friends of chronically ill adults.
Family members and friends can be an important source of self-management support for older adults with chronic diseases. We characterized the U.S. population of potential and current "disease management supporters" for people with chronic illness who are independent in activities of daily living, the help that supporters could provide, and barriers to increasing support. We used a nationally representative survey of U.S. adults (N = 1,722). Forty-four percent of respondents (representing 100 million US adults) help a family member or friend with chronic disease management; another 9% (representing 21 million U.S. adults) are willing to start. Most are willing to assist with key tasks such as medication use and communicating with providers, although they feel constrained by privacy concerns and a lack of patient health information. The majority of U.S. adults already helps, or would be willing to help, one of their family members or friends with chronic illness care. Supporters' specific concerns could be addressed through innovative programs.


Early-versus late-onset sepsis in neonates - time to shift the paradigm?
Neonatal sepsis is traditionally classified as early-onset sepsis (EOS) and late-onset sepsis (LOS) disease categories. This paradigm was based on observed epidemiological data from high income settings. However, increasing availability of microbiology results from diverse settings challenges these assumptions, necessitating re-examination of neonatal sepsis classifications. To review the literature describing the aetiology of EOS and LOS in hospitalized neonates with stratification of pathogen spectrum by low- (LIC), middle- (MIC) and high-income (HIC) country settings, to critically re-examine the continued appropriateness of the 'EOS vs. LOS' sepsis paradigm in all settings. PubMed was searched for peer-reviewed English full-text articles published from inception up until 8 August 2022. Studies often report on either EOS or LOS, rather than both. We identified only 49 original articles reporting on pathogen distribution of both EOS and LOS in the same hospital setting. Clear differences in sepsis aetiology were shown between LIC, MIC and HIC settings, with increasing importance of Klebsiella pneumoniae and decreasing importance of Group B Streptococcus in the first 72 hours of life in LIC and MIC. The concept of 'EOS vs. LOS' may be less useful for predicting the pathogen spectrum of neonatal sepsis in LIC and MIC, but the paradigm has shaped reporting of neonatal sepsis, and our understanding. Future neonatal sepsis reporting should utilize strengthening the reporting of observational studies in epidemiology for newborn infection (STROBE-NI) reporting guidelines and clearly describe timing of infection by day, and variation in pathogen spectrum across the neonatal period. Data identified in this review challenge the generalizability of the prevailing EOS/LOS paradigm in LIC and MIC.


Role of GABAB receptor-mediated inhibition in reciprocal interareal pathways of rat visual cortex.
In neocortex, synaptic inhibition is mediated by gamma-aminobutyric acid-A (GABAA) and GABAB receptors. By using intracellular and patch-clamp recordings in slices of rat visual cortex we studied the balance of excitation and inhibition in different intracortical pathways. The study was focused on the strength of fast GABAA- and slow GABAB-mediated inhibition in interareal forward and feedback connections between area 17 and the secondary, latero-medial visual area (LM). Our results demonstrate that in most layer 2/3 neurons forward inputs elicited excitatory postsynaptic potentials (EPSPs) that were followed by fast GABAA- and slow GABAB-mediated hyperpolarizing inhibitory postsynaptic potentials (IPSPs). These responses resembled those elicited by horizontal connections within area 17 and those evoked by stimulation of the layer 6/white matter border. In contrast, in the feedback pathway hyperpolarizing fast and slow IPSPs were rare. However weak fast and slow IPSPs were unmasked by bath application of GABAB receptor antagonists. Because in the feedback pathway disynaptic fast and slow IPSPs were rare, polysynaptic EPSPs were more frequent than in forward, horizontal, and interlaminar circuits and were activated over a broader stimulus range. In addition, in the feedback pathway large-amplitude polysynaptic EPSPs were longer lasting and showed a late component whose onset coincided with that of slow IPSPs. In the forward pathway these late EPSPs were only seen with stimulus intensities that were below the activation threshold of slow IPSPs. Unlike strong forward inputs, feedback stimuli of a wide range of intensities increased the rate of ongoing neuronal firing. Thus, when forward and feedback inputs are simultaneously active, feedback inputs may provide late polysynaptic excitation that can offset slow IPSPs evoked by forward inputs and in turn may promote recurrent excitation through local intracolumnar circuits. This may provide a mechanism by which feedback inputs from higher cortical areas can amplify afferent signals in lower areas.


Effect of suckling isotonic or hypertonic solutions of sodium bicarbonate or glucose on abomasal emptying rate in calves.
To determine and compare the abomasal emptying rates in calves suckling milk replacer or an isotonic or hypertonic solution of NaHCO(3) or glucose. 5 male Holstein-Friesian calves that were < 30 days of age. Calves were fed 2 L of milk replacer or isotonic (300 mOsm/L) or hypertonic (600 mOsm/L) solutions of NaHCO(3) or glucose containing acetaminophen (50 mg/kg). Venous blood samples and transabdominal ultrasonographic abomasal dimensions were obtained periodically after feeding, and abomasal luminal pH was continuously monitored by placement of a luminal pH electrode through an abomasal cannula. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration, ultrasonographic determination of the half-time of abomasal emptying, and the time for luminal pH to return to within 1 pH unit of the preprandial value. Hypertonic NaHCO(3) solution was emptied slower than an isotonic NaHCO(3) solution, isotonic glucose solution was emptied slower than an isotonic NaHCO(3) solution, and hypertonic glucose solution emptied slower than an isotonic glucose solution. An electrolyte solution for oral administration with a high osmolarity and glucose concentration may lead to a slower resuscitation of dehydrated diarrheic calves because such solutions decrease the abomasal emptying rate and therefore the rate of solution delivery to the small intestine. Whether slowing of the abomasal emptying rate in dehydrated diarrheic calves suckling an oral electrolyte solution is clinically important remains to be determined.


Leaching behaviour of copper slag, construction and demolition waste and crushed rock used in a full-scale road construction.
The leaching behaviour of a road construction with fayalitic copper slag, recycled concrete and crushed rock as sub-base materials was monitored over ten years. All studied materials used in the road construction, including crushed rock, contained concentrations of several elements exceeding the guideline values recommended by the Swedish EPA for total element concentrations for waste materials used in constructions. Despite that, leaching from the road construction under field conditions in general was relatively low. The leachates from the recycled materials contained higher concentrations of several constituents than the leachates from the reference section with crushed rock. The leaching of the elements of interest (Cr, Mo, Ni, Zn) reached peak concentrations during the second and fourth (Cu) years and decreased over the observation period to levels below the Swedish recommended values. Carbonation of the concrete aggregates caused a substantial but short-term increase in the leaching of oxyanions such as chromate. The environmental risks related to element leaching are highest at the beginning of the road life. Ageing of materials or pre-treatment through leaching is needed prior to their use in construction to avoid peak concentrations. Also, the design of road constructions should be adjusted so that recycled materials are covered with low-permeability covers, which would minimize the exposure to atmospheric precipitation and weathering.


Whole-exome sequencing to decipher the genetic heterogeneity of hearing loss in a Chinese family with deaf by deaf mating.
Inherited deafness has been shown to have high genetic heterogeneity. For many decades, linkage analysis and candidate gene approaches have been the main tools to elucidate the genetics of hearing loss. However, this associated study design is costly, time-consuming, and unsuitable for small families. This is mainly due to the inadequate numbers of available affected individuals, locus heterogeneity, and assortative mating. Exome sequencing has now become technically feasible and a cost-effective method for detection of disease variants underlying Mendelian disorders due to the recent advances in next-generation sequencing (NGS) technologies. In the present study, we have combined both the Deafness Gene Mutation Detection Array and exome sequencing to identify deafness causative variants in a large Chinese composite family with deaf by deaf mating. The simultaneous screening of the 9 common deafness mutations using the allele-specific PCR based universal array, resulted in the identification of the 1555A>G in the mitochondrial DNA (mtDNA) 12S rRNA in affected individuals in one branch of the family. We then subjected the mutation-negative cases to exome sequencing and identified novel causative variants in the MYH14 and WFS1 genes. This report confirms the effective use of a NGS technique to detect pathogenic mutations in affected individuals who were not candidates for classical genetic studies.


Steady-state simulations using weighted ensemble path sampling.
We extend the weighted ensemble (WE) path sampling method to perform rigorous statistical sampling for systems at steady state. A straightforward steady-state implementation of WE is directly practical for simple landscapes, but not when significant metastable intermediates states are present. We therefore develop an enhanced WE scheme, building on existing ideas, which accelerates attainment of steady state in complex systems. We apply both WE approaches to several model systems, confirming their correctness and efficiency by comparison with brute-force results. The enhanced version is significantly faster than the brute force and straightforward WE for systems with WE bins that accurately reflect the reaction coordinate(s). The new WE methods can also be applied to equilibrium sampling, since equilibrium is a steady state.


Infections with Pneumocystis carinii.
Studies were reviewed on attempts to apply serologic methods for the laboratoary diagnosis of pneumocystis pneumonia and for epidemiologic surveillance in outbreaks of this disease. At autopsy the parasite was found in 7.7% of patients with a clinically latent infection. In this series of patients, parasitologic findings were not correlated with the results of a complement fixation (CF) test or with those of an indirect fluorescent antibody test. The high incidence of serologic reactivity in the CF test in chronic obstructive lung disease was not related with special clinical symptoms. Longitudinally performed parasitologic and serologic observations will be needed to find out if Pneumocystis carinii is a pathogen and fulfills Koch's criteria. Preliminary data are given for such an experimental approach in a colony of rats.


A method for time-resolved measurements of the mechanics of phagocytic cups.
The internalization of matter by phagocytosis is of key importance in the defence against bacterial pathogens and in the control of cancerous tumour growth. Despite the fact that phagocytosis is an inherently mechanical process, little is known about the forces and energies that a cell requires for internalization. Here, we use functionalized magnetic particles as phagocytic targets and track their motion while actuating them in an oscillating magnetic field, in order to measure the translational and rotational stiffnesses of the phagocytic cup as a function of time. The measured evolution of stiffness reveals a characteristic pattern with a pronounced peak preceding the finalization of uptake. The measured stiffness values and their time dependence can be interpreted with a model that describes the phagocytic cup as a prestressed membrane connected to an elastically deformable actin cortex. In the context of this model, the stiffness peak is a direct manifestation of a previously described mechanical bottleneck, and a comparison of model and data suggests that the membrane advances around the particle at a speed of about 20 nm s(-1). This approach is a novel way of measuring the progression of emerging phagocytic cups and their mechanical properties in situ and in real time.


Synthesis and structural elucidation of solvent-free and solvated lithium dimethyl (HMDS) zincates.
Using a co-complexation methodology the unsolvated lithium zincate [LiZn(HMDS)Me2] ( 4, HMDS = 1,1,1,3,3,3-hexamethyldisilazide) was prepared by reaction of an equimolar amount of LiHMDS with Me2Zn in a non-polar toluene-hexane solvent mixture. X-Ray crystallographic studies reveal that the asymmetric unit of 4 has a dinuclear arrangement, based on a planar LiNZnC four-membered ring. As a result of intermolecular interactions between the lithium centre of one asymmetric unit and a terminal methyl group of another, 4 presents a polymeric chain array in the solid state. DFT calculations revealed that the formation of the polymer is the driving force for the success of co-complexation of LiHMDS and Me2Zn to yield the unsolvated zincate 4. The reaction of 4 with PMDETA (N,N,N,N,N-pentamethyldiethylenetriamine) afforded the new solvated zincate [(PMDETA)Li(mu-Me)Zn(HMDS)Me] ( 5). X-Ray crystallographic studies show that the asymmetric unit of 5 consists of an open, dinuclear LiCZnC arrangement rather than a closed cyclic one, in which the HMDS ligand unusually occupies a terminal position on Zn. DFT computational studies showed that the structure found for 5 was energetically preferred to the expected HMDS-bridging isomer due to the steric hindrance imposed by the tridentate PMDETA ligand. The reaction of 4 with the neutral nitrogen donors 4-tert-butylpyridine and tert-butylcyanide afforded the homometallic compounds [(tBu-pyr)Li(HMDS)] ( 6) and [(tBuCN)Li(HMDS)] ( 7) respectively as a result of disproportionation reactions. Compounds 6 and 7 were characterized by NMR (1H, 13C and 7Li) spectroscopy.


Gekkonid lizards adapt fat storage to desert environments.
Coleonyx v. variegatus is adapted to feed voraciously after deprivation of food and to withstand long periods without food. In 4 days specimens converted enough food into reserves to increase their weight by about 50 percent. Total deprivation of food resulted in very gradual loss of weight, which, if maintained, would result in 4 days of feeding being sufficient to sustain the animal for periods of 6 to 9 months.


Intraspecific and interspecific adaptive latitudinal cline in Brassicaceae seed oil traits.
Nearly all seed plants rely on stored seed reserves before photosynthesis can commence. Natural selection for seed oil traits must have occurred over 319 million years of evolution since the first seed plant ancestor. Accounting for the biogeographic distribution of seed oil traits is fundamental to understanding the mechanisms of adaptive evolution in seed plants. However, the evolution of seed oils is poorly understood. We provide evidence of the adaptive nature of seed oil traits at the intraspecific and interspecific levels in Brassicaceae-an oilseed-rich and economically important plant family. Univariate statistics, Pearson's correlation, multiple regression, generalized linear mixed model analysis, and phylogenetic autocorrelation tests on seed oil traits of 360 accessions of Arabidopsis thaliana and 216 Brassicaceae species helped provide evidence of the adaptive nature of seed oil traits. At higher latitudes, both seed oil content and unsaturated fatty acids have selective advantages in Arabidopsis thaliana (intraspecific-level), while only unsaturated fatty acids have selective advantages across 216 Brassicaceae species (interspecific-level). The seed oil patterns fit within the theoretical framework of the gradient model. Seed oil content increases significantly from temperate to subtropical to tropical regions in Brassicaceae herbs. Absence of phylogenetic signals for seed oil traits and high seed oil content in four tribes of Brassicaceae were observed. Multiple seed oil traits are adaptive in nature and follow a gradient model. Consistent evolutionary patterns of seed oil traits were observed at the intraspecific and interspecific levels in Brassicaceae. Seed oil traits change with latitude and across biomes, suggesting selection. The absence of a phylogenetic signal for seed oil traits and the occurrence of high seed oil content in four Brassicaceae tribes provides evidence of the adaptive nature of seed oil traits in Brassicaceae.


Foreign Body Response to Silicone in Cochlear Implant Electrodes in the Human.
Silicone as part of a cochlear implant electrode may be responsible for a foreign body response in the human. Clinical evidence of a foreign body response to a cochlear implant has been reported. In a previous study, particulate material found within the fibrous sheath and within macrophages surrounding a cochlear implant has been identified as being consistent with platinum. However, to date, there has been no histologic evidence of a role for silicone in this cellular immune response. A total of 44 temporal bone specimens from 36 patients were reviewed by light microscopy for evidence of presumed platinum and/or silicone foreign bodies in an extracellular or intracellular location. Identification of cell type involved in phagocytosis of foreign body material was accomplished using CD163 immunostaining. The identity and source of the foreign body material was confirmed using energy-dispersive X-ray spectroscopy and scanning electron microscopy. Evidence for both platinum and silicone was found in all 44 specimens. In three patients, anti-CD 163 immunostaining demonstrated phagocytized platinum and silicone foreign bodies. In five specimens, energy-dispersive X-ray spectroscopy demonstrated that the birefringent foreign bodies were consistent with silicone. Scanning electron microscopy of two electrodes removed from temporal bones demonstrated small cracks, fragmentation, and small circular defects in the silicone carrier. Histologic evidence of a foreign body response to the presence of platinum and silicone in a cochlear implant has been demonstrated and may be responsible for some reported delayed failures or extrusion.


Impact of the COVID-19 pandemic on teaching and learning in health professional education: a mixed methods study protocol.
Due to the complex nature of healthcare professionals' roles and responsibilities, the education of this workforce is multifaceted and challenging. It relies on various sources of learning from teachers, peers, patients and may focus on Work Integrated Learning (WIL). The COVID-19 pandemic has impacted many of these learning opportunities especially those in large groups or involving in person interaction with peers and patients. Much of the curriculum has been adapted to an online format, the long-term consequence of which is yet to be recognized. The changed format is likely to impact learning pedagogy effecting both students and teachers. This requires a systematic approach to evaluation of online teaching and learning adaptation, in comparison to the previous format, where, in person education may have been the focus. The proposed study is a broad based evaluation of health professional education in a major Australian University. The protocol describes a mixed methods convergent design to evaluate the impact of online education on students and teachers in health professional courses including Medicine, Nursing, Allied Health and Biomedical Science. A framework, developed at the university, using Contribution Analysis (CA), will guide the evaluation. Quantitative data relating to student performance, student evaluation of units, quantity of teaching activities and resource utilization will be collected and subjected to relevant statistical analysis. Data will be collected through surveys (500 students and 100 teachers), focus groups (10 groups of students) and interviews of students and teachers (50 students beyond graduation and 25 teachers, for long term follow up to 12 months). Application of CA will be used to answer the key research questions on the short term and long-term impact of online education on teaching and learning approaches. The protocol describes the study, which will be widely implemented over the various courses in Health Professional Education and Biomedical Science. It will evaluate how students and teachers engage with the online delivery of the curriculum, student performance, and resources used to implement these changes. It also aims to evaluate longitudinal outcome of student learning attributes and impact on graduate outcomes, which is poorly reported in educational literature.


Recurrent primary vulvovaginal malignant melanoma arising in melanoma in situ--the natural history of lesions followed for 23 years.
Multifocal melanoma and melanoma in situ of the vulva and vagina are uncommon lesions, and our understanding of their natural history is limited. Vulvovaginal melanoma appears to be biologically different from cutaneous melanoma and has more in common with mucosal melanoma. A 60-year-old woman presented in 1977 with a pigmented vulvar lesion. Histologic examination revealed melanoma in situ associated with focal invasive melanoma. She re-presented with recurrent primary melanomas arising in melanoma in situ in 1990 and 1998 and died of widespread metastatic melanoma in 2000. Melanoma in situ of the vulva and vagina is rare and appears to have a relatively slow but definite progression to invasive melanoma. All suspicious pigmented lesions in this region should be biopsied, and if multifocal in situ melanoma is identified, vulvo(vagin)ectomy should be considered.


Predicting potentially hazardous chemical reactions using an explainable neural network.
Predicting potentially dangerous chemical reactions is a critical task for laboratory safety. However, a traditional experimental investigation of reaction conditions for possible hazardous or explosive byproducts entails substantial time and cost, for which machine learning prediction could accelerate the process and help detailed experimental investigations. Several machine learning models have been developed which allow the prediction of major chemical reaction products with reasonable accuracy. However, these methods may not present sufficiently high accuracy for the prediction of hazardous products which particularly requires a low false negative result for laboratory safety in order not to miss any dangerous reactions. In this work, we propose an explainable artificial intelligence model that can predict the formation of hazardous reaction products in a binary classification fashion. The reactant molecules are transformed into substructure-encoded fingerprints and then fed into a convolutional neural network to make the binary decision of the chemical reaction. The proposed model shows a false negative rate of 0.09, which can be compared with 0.47-0.66 using the existing main product prediction models. To provide explanations for what substructures of the given reactant molecules are important to make a decision for target hazardous product formation, we apply an input attribution method, layer-wise relevance propagation, which computes the contributions of individual inputs per input data. The computed attributions indeed match some of the existing chemical intuitions and mechanisms, and also offer a way to analyze possible data-imbalance issues of the current predictions based on relatively small positive datasets. We expect that the proposed hazardous product prediction model will be complementary to existing main product prediction models and experimental investigations.


Designing and conducting randomized controlled trials in palliative care: A summary of discussions from the 2010 clinical research forum of the Australian Palliative Care Clinical Studies Collaborative.
Rigorous clinical research in palliative care is challenging but achievable. Trial participants are likely to have deteriorating performance status, co-morbidities and progressive disease. It is difficult to recruit patients, and attrition unrelated to the intervention being trialled is high. The aim of this paper is to highlight practical considerations from a forum held to discuss these issues by active palliative care clinical researchers. To date, the Australian Palliative Care Clinical Studies Collaborative (PaCCSC) has randomized more than 500 participants across 12 sites in 8 Phase III studies. Insights from the 2010 clinical research forum of the PaCCSC are reported. All active Australian researchers in palliative care were invited to present their current research and address three specific questions: (1) What has worked well? (2) What didn't work well? and (3) How should the research be done differently next time? Fourteen studies were presented, including six double-blind, randomized, controlled, multi-site trials run by the PaCCSC. Key recommendations are reported, including guidance on design; methodologies; and strategies for maximizing recruitment and retention. These recommendations will help to inform future trial design and conduct in palliative care.


Tongue cooling: a new reward for thirsty rodents.
Thirsty rodents will persistently lick a stream of dry air pumped through a standard drinking tube. This air-licking is attenuated by experimental manipulations which reduce the evaporative cooling of the tongue and mouth produced by the airstream. This suggests that such cooling is itself an effective reward for thirstry rodents. We tested this hypothesis by presenting thirsty rodents with a piece of cold, dry metal. Different species spent from 9 to 40 percent of their session time licking the cold metal. When deprived of water hamsters reared from birth without access to drinking water licked cold metal in preference to metal maintained at room or body temperature. This preference was approximately equal to that of littermates reared normally. We conclude that tongue cooling is a primary reward for thirsty rodents.


The same frequency of planets inside and outside open clusters of stars.
Most stars and their planets form in open clusters. Over 95 per cent of such clusters have stellar densities too low (less than a hundred stars per cubic parsec) to withstand internal and external dynamical stresses and fall apart within a few hundred million years. Older open clusters have survived by virtue of being richer and denser in stars (1,000 to 10,000 per cubic parsec) when they formed. Such clusters represent a stellar environment very different from the birthplace of the Sun and other planet-hosting field stars. So far more than 800 planets have been found around Sun-like stars in the field. The field planets are usually the size of Neptune or smaller. In contrast, only four planets have been found orbiting stars in open clusters, all with masses similar to or greater than that of Jupiter. Here we report observations of the transits of two Sun-like stars by planets smaller than Neptune in the billion-year-old open cluster NGC6811. This demonstrates that small planets can form and survive in a dense cluster environment, and implies that the frequency and properties of planets in open clusters are consistent with those of planets around field stars in the Galaxy.


The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials.
In two double-blind trials conducted in North America, 513 patients with chronic schizophrenia received risperidone, haloperidol, or placebo. In the present study, combined data from the two trials were analyzed. Patients were randomly assigned to receive placebo, fixed doses of risperidone (2, 6, 10, and 16 mg/day) or 20 mg/day of haloperidol for 8 weeks. Factor analysis of scores on the Positive and Negative Syndrome Scale (PANSS) produced five dimensions (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression), similar to the five dimensions of previous factor-analytic studies of PANSS data. Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncontrolled hostility/excitement, and anxiety/depression. Even at the lowest dose, 2 mg/day, risperidone was significantly (p < or = .05) superior to haloperidol in reducing negative symptoms. The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms. Risperidone produced significantly (p < or = .05) greater improvements than haloperidol on all five dimensions. The large between-group differences on negative symptoms, hostility/excitement, and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents.


Receptor-mediated gonadotropin action in the ovary. Inhibitory actions of concanavalin A and wheat-germ agglutinin on gonadotropin-stimulated cyclic AMP and progesterone responses in ovarian cells.
Pretreatment of ovarian cells with concanavalin A and wheat-germ agglutinin blocked the gonadotropin-induced cyclic AMP and progesterone responses and this effect was time- and concentration-dependent. Basal production of either cyclic AMP or progesterone, however, was not affected by treatment of cells with lectin. The effect of concanavalin A on gonadotropin-mediated cyclic AMP and progesterone responses was blocked by alpha-methyl D-mannoside and alpha-methyl d-glucoside. Similarly the inhibitory effect of wheat-germ agglutinin was reversed by N-acetyl-D-glucosamine. Pretreatment of ovarian cells with concanavalin A or wheat-germ agglutinin had no effect on protein synthesis in the ovary as monitored by [3H]proline incorporation studies. Concanavalin A and wheat-germ agglutinin did not affect steroid production in response to dibutyryl cyclic AMP and 8-bromo cyclic AMP, indicating that the inhibitory action of lectin was occurring at a step before cyclic AMP formation. Lectins specific for L-fucose, D-galactose and N-acetyl-D-galactosamine, gorse seed agglutinin, peanut agglutinin and Dolichos biflorus agglutinin respectively, did not interfere with gonadotropin-induced cyclic AMP and progesterone responses. The present studies suggest that gonadotropin receptors may be glycoprotein in nature or closely associated with glycoprotein structures with the carbohydrate chain containing N-acetyl-D-glucosamine, mannose and possibly N-acetylneuraminic acid.


Measurement technique for in situ characterizing aberrations of projection optics in lithographic tools.
As the feature size decreases, degradation of image quality caused by wavefront aberrations of projection optics in lithographic tools has become a serious problem in the low-k1 process. We propose a novel measurement technique for in situ characterizing aberrations of projection optics in lithographic tools. Considering the impact of the partial coherence illumination, we introduce a novel algorithm that accurately describes the pattern displacement and focus shift induced by aberrations. Employing the algorithm, the measurement condition is extended from three-beam interference to two-, three-, and hybrid-beam interferences. The experiments are performed to measure the aberrations of projection optics in an ArF scanner.


Comparison of Stakeholder Metrics for Traditional and Adaptive Development and Licensing Approaches to Drug Development.
This study evaluates whether an adaptive development and licensing approach to drug development, compared with approaches widely used today, might have tangible advantages across stakeholder groups, thereby facilitating the future adoption. Details involving actual and modeled clinical development and licensing programs for 3 case studies were used as inputs into a discounted cash flow spreadsheet model. Outputs included net present value and expected net present value, which are metrics considered as key incentives for pharmaceutical developers, and change in patient access over the product life and numbers of appropriately and inappropriately treated patients, which are metrics considered as key incentives for regulators, patients, and prescribers. Actual and modeled development programs were compared using an "adaptiveness" scoring algorithm. Generally, the more adaptive programs correlated with more favorable stakeholder outcomes. However, favorable outcomes may be overwhelmed in some cases, and the causative conditions and stakeholder reactions need to be defined.


Oesophageal malignancies in Dar es Salaam.
The clinical, radiological, endoscopic and histological aspects of 46 oesophageal cancers seen over a period of three years are analysed. A history of dysphagia was obtained in 93% of the cases while 87% of them had evident weight loss of varying degrees, making the two the most consistent clinical features; 24% of patients had pulmonary complications. The lower third of the oesophagus was the commonest location of tumours, accounting for 63% of the cases, while 61% of all cancers were of the squamous cell histological variety. Six biopsy specimens yielded negative histology, although the endoscopic visualization and radiological features were consistent with malignant growths.


Interactions of quercetin with receptor tyrosine kinases associated with human lung carcinoma.
Lung cancer is a deadly form of cancer with high morbidity and mortality rates. Deregulated receptor tyrosine kinases (RTKs) are frequently associated with the formation and development of lung carcinoma. Quercetin is a major dietary flavonoid that has been shown to induce cell growth inhibition and apoptosis in human lung cancer cell lines. In the current study, four major overexpressed RTKs - EGFR, FGFR1, IGF1R and c-Met - involved in human lung cancer were investigated. Molecular docking was employed to identify the binding orientation and inhibitory potential of quercetin in these RTKs. Quercetin bound to the ATP binding pocket of these kinases exhibited good binding scores and interactions by establishing hydrogen, hydrophobic and π-π interactions with the hinge region and the DFG motif in the activation loop. Thus, quercetin could be further explored as a platform for developing specific or polypharmacological compounds targeting overexpressed RTKs in lung cancer.


Performance evaluation of the ECAT HRRT: an LSO-LYSO double layer high resolution, high sensitivity scanner.
The ECAT high resolution research tomograph (HRRT) is a dedicated brain and small animal PET scanner, with design features that enable high image spatial resolution combined with high sensitivity. The HRRT is the first commercially available scanner that utilizes a double layer of LSO/LYSO crystals to achieve photon detection with depth-of-interaction information. In this study, the performance of the commercial LSO/LYSO HRRT was characterized, using the NEMA protocol as a guideline. Besides measurement of spatial resolution, energy resolution, sensitivity, scatter fraction, count rate performance, correction for attenuation and scatter, hot spot recovery and image quality, a clinical evaluation was performed by means of a HR+/HRRT human brain comparison study. Point source resolution varied across the field of view from approximately 2.3 to 3.2 mm (FWHM) in the transaxial direction and from 2.5 to 3.4 mm in the axial direction. Absolute line-source sensitivity ranged from 2.5 to 3.3% and the NEMA-2001 scatter fraction equalled 45%. Maximum NECR was 45 kcps and 148 kcps according to the NEMA-2001 and 1994 protocols, respectively. Attenuation and scatter correction led to a volume uniformity of 6.3% and a system uniformity of 3.1%. Reconstructed values deviated up to 15 and 8% in regions with high and low densities, respectively, which can possibly be assigned to inaccuracies in scatter estimation. Hot spot recovery ranged from 60 to 94% for spheres with diameters of 1 to 2.2 cm. A high quantitative agreement was met between HR+ and HRRT clinical data. In conclusion, the ECAT HRRT has excellent resolution and sensitivity properties, which is a crucial advantage in many research studies.


Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021.
Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.


Renal insufficiency is an independent predictor of in-hospital mortality for patients with acute myocardial infarction receiving primary percutaneous coronary intervention.
To investigate the relationship between renal function and clinical outcomes among patients with acute ST-segment elevation myocardial infarction (ASTEMI), who were treated with emergency percutaneous coronary intervention (PCI). 420 patients hospitalized in Peking University First Hospital, diagnosed with ASTEMI treated with emergency (PCI) from January 2001 to June 2011 were enrolled in this study. Estimated glomerular filtration rate (eGFR) was used as a measure of renal function. We compared the clinical parameters and outcomes between ASTEMI patients combined renal insufficiency and the patients with normal renal function. There was a significant increase in the concentrations of fibrinogen and D-Dimer (P<0.05) and a much higher morbidity of diabetes mellitus in the group of patients with chronic kidney disease (CKD; eGFR<60 ml/(min·1.73 m(2))) (P<0.01). CKD (eGFR<60 ml/(min·1.73 m(2))) was an independent predictor of in-hospital mortality for patients hospitalized with ASTEMI receiving PCI therapy rapidly (P=0.032, odds ratio (OR) 4.159, 95% confidence interval (CI) 1.127-15.346). Renal insufficiency is an independent predictor of in-hospital mortality for patients hospitalized with ASTEMI treated with primary PCI.


Monitoring medication optimization in patients with Parkinson's disease.
Medication optimization is a common component of the treatment strategy in patients with Parkinson's disease. As the disease progresses, it is essential to compensate for the movement deterioration in patients. Conventionally, examining motor deterioration and prescribing medication requires the patient's onsite presence in hospitals or practices. Home-monitoring technologies can remotely deliver essential information to physicians and help them devise a treatment decision according to the patient's need. Additionally, they help to observe the patient's response to these changes. In this regard, we conducted a longitudinal study to collect gait data of patients with Parkinson's disease while they received medication changes. Using logistic regression classifier, we could detect the annotated motor deterioration during medication optimization with an accuracy of 92%. Moreover, an in-depth examination of the best features illustrated a decline in gait speed and swing phase duration in the deterioration phases due to suboptimal medication.Clinical relevance- Our proposed gait analysis method in this study provides objective, detailed, and punctual information to physicians. Revealing clinically relevant time points related to the patient's need for medical adaption alleviates therapy optimization for physicians and reduces the duration of suboptimal treatment for patients. As the home-monitoring system acts remotely, embedding it in the medical care pathways could improve patients' quality of life.


[Characteristics of lymphocyte enzymatic activity in children with Epstein-Barr infection].
Activity of NAD(P)-dependent dehydrogenases in peripheral blood lymphocytes from 140 children aged 1-14 years with Epstein-Barr infection was studied. It was shown to depend on the disease duration and children's age. Disturbances of lymphocyte enzymatic activity persisted during the reconvalescence period.


Global economic costs of aquatic invasive alien species.
Much research effort has been invested in understanding ecological impacts of invasive alien species (IAS) across ecosystems and taxonomic groups, but empirical studies about economic effects lack synthesis. Using a comprehensive global database, we determine patterns and trends in economic costs of aquatic IAS by examining: (i) the distribution of these costs across taxa, geographic regions and cost types; (ii) the temporal dynamics of global costs; and (iii) knowledge gaps, especially compared to terrestrial IAS. Based on the costs recorded from the existing literature, the global cost of aquatic IAS conservatively summed to US$345 billion, with the majority attributed to invertebrates (62%), followed by vertebrates (28%), then plants (6%). The largest costs were reported in North America (48%) and Asia (13%), and were principally a result of resource damages (74%); only 6% of recorded costs were from management. The magnitude and number of reported costs were highest in the United States of America and for semi-aquatic taxa. Many countries and known aquatic alien species had no reported costs, especially in Africa and Asia. Accordingly, a network analysis revealed limited connectivity among countries, indicating disparate cost reporting. Aquatic IAS costs have increased in recent decades by several orders of magnitude, reaching at least US$23 billion in 2020. Costs are likely considerably underrepresented compared to terrestrial IAS; only 5% of reported costs were from aquatic species, despite 26% of known invaders being aquatic. Additionally, only 1% of aquatic invasion costs were from marine species. Costs of aquatic IAS are thus substantial, but likely underreported. Costs have increased over time and are expected to continue rising with future invasions. We urge increased and improved cost reporting by managers, practitioners and researchers to reduce knowledge gaps. Few costs are proactive investments; increased management spending is urgently needed to prevent and limit current and future aquatic IAS damages.


Composite Interval Mapping Based on Lattice Design for Error Control May Increase Power of Quantitative Trait Locus Detection.
Experimental error control is very important in quantitative trait locus (QTL) mapping. Although numerous statistical methods have been developed for QTL mapping, a QTL detection model based on an appropriate experimental design that emphasizes error control has not been developed. Lattice design is very suitable for experiments with large sample sizes, which is usually required for accurate mapping of quantitative traits. However, the lack of a QTL mapping method based on lattice design dictates that the arithmetic mean or adjusted mean of each line of observations in the lattice design had to be used as a response variable, resulting in low QTL detection power. As an improvement, we developed a QTL mapping method termed composite interval mapping based on lattice design (CIMLD). In the lattice design, experimental errors are decomposed into random errors and block-within-replication errors. Four levels of block-within-replication errors were simulated to show the power of QTL detection under different error controls. The simulation results showed that the arithmetic mean method, which is equivalent to a method under random complete block design (RCBD), was very sensitive to the size of the block variance and with the increase of block variance, the power of QTL detection decreased from 51.3% to 9.4%. In contrast to the RCBD method, the power of CIMLD and the adjusted mean method did not change for different block variances. The CIMLD method showed 1.2- to 7.6-fold higher power of QTL detection than the arithmetic or adjusted mean methods. Our proposed method was applied to real soybean (Glycine max) data as an example and 10 QTLs for biomass were identified that explained 65.87% of the phenotypic variation, while only three and two QTLs were identified by arithmetic and adjusted mean methods, respectively.


[Electroconvulsive therapy--sources of error and aids in insufficient duration of convulsions].
Modern electroconvulsive therapy (ECT) involves the administration of six to ten convulsions of sufficient duration (25 seconds) by unilateral electrical stimulation of the non-dominant hemisphere. Missed or abortive seizures are a common clinical problem but may often be accounted for by concurrent medication and technical problems with unilateral ECT seizure induction. In the absence of such factors, controlled hyperventilation and intravenous caffeine are adjunctive means to achieve an adequate unilateral ECT treatment course.


Attenuation of neurovirulence of Theiler's murine encephalomyelitis virus strain GDVII is not sufficient to establish persistence in the central nervous system.
Virus recombinants constructed from Theiler's murine encephalomyelitis virus (TMEV) strain GDVII, which causes a rapidly fatal encephalitis in mice, and the less virulent BeAn, which persists in the murine central nervous system (CNS) and causes inflammatory demyelination, and a GDVII mutant deleted of 46 of 76 leader protein amino acids were analysed for virus persistence in the CNS. The two recombinant and mutant viruses principally contain GDVII sequences including the nucleotides encoding the polyprotein and 3' untranslated region. These viruses were found to replicate in the CNS of mice but they did not produce acute encephalitis or paralysis, i.e. they were attenuated in neurovirulence compared to the GDVII parent. More important, none of the viruses persisted in the mouse CNS nor caused chronic demyelination. Thus, attenuation of GDVII neurovirulence alone is not sufficient to establish TMEV persistence. This result is discussed in the context of a genomic determinant for persistence.


Assessment of topical hypopigmenting agents on solar lentigines of Asian women.
So-called darkened age spots encompass distinct pathological processes. The efficacy of topical depigmenting agents is difficult to objectivate. To assess the hypopigmenting effect of three cosmetic formulations using objective biometrological methods. 50 women of South-East Asian ancestry were enrolled in this pilot study. They had solar lentigines according to dermoscopic criteria. The lesions were treated by topical hypopigmenting formulations. Products were applied twice daily for 2 or 3 months. Assessments at 1-month intervals were made using narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light reflection and photodensitometry- and image-analysis-assisted corneomelametry. A 20% azelaic acid formulation and another one containing 5% ascorbyl glucosamine, 1% kojic acid and alpha-hydroxyacid esters appeared inefficacious on solar lentigines. A stabilized soy extract showed a better although modest lightening effect when assessed by corneomelametry. The subclinical or faint mottled skin revealed by ultraviolet light examination better responded (p < 0.05) to treatments. Focal epidermal hyperpigmentation is better controlled by topical whitening agents when the increase in melanin content reflects a modest functional hyperactivity of melanocytes.


Effects of food policy actions on Indigenous Peoples' nutrition-related outcomes: a systematic review.
Indigenous Peoples worldwide endure unacceptable health disparities with undernutrition and food insecurity often coexisting with obesity and chronic diseases. Policy-level actions are required to eliminate malnutrition in all its forms. However, there has been no systematic synthesis of the evidence of effectiveness of food and nutrition policies for Indigenous Peoples around the world. This review fills that gap. Eight databases were searched for peer-reviewed literature, published between 2000 and 2019. Relevant websites were searched for grey literature. Articles were included if they were original studies, published in English and included data from Indigenous Peoples from Western colonised countries, evaluated a food or nutrition policy (or intervention), and provided quantitative impact/outcome data. Study screening, data extraction and quality assessment were undertaken independently by two authors, at least one of whom was Indigenous. A narrative synthesis was undertaken with studies grouped according to the NOURISHING food policy framework. We identified 78 studies from Canada, Australia, Aotearoa/New Zealand and the USA. Most studies evaluated targeted interventions, focused on rural or remote Indigenous communities. The most effective interventions combined educational strategies with policies targeting food price, composition and/or availability, particularly in retail and school environments. Interventions to reduce exposure to unhealthy food advertising was the only area of the NOURISHING framework not represented in the literature. Few studies examined the impact of universal food policies on Indigenous Peoples' diets, health or well-being. Both targeted and universal policy action can be effective for Indigenous Peoples. Actions that modify the structures and systems governing food supply through improved availability, access and affordability of healthy foods should be prioritised. More high-quality evidence on the impact of universal food and nutrition policy actions for Indigenous Peoples is required, particularly in urban areas and in the area of food marketing.


Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with an external ventricular drain.
Owing to its antibacterial properties, ceftaroline could be attractive for prevention or treatment of bacterial post-neurosurgical meningitis/ventriculitis. However, few data are available concerning its meningeal concentrations. To investigate ceftaroline CSF pharmacokinetics in ICU patients with an external ventricular drain (EVD). Patients received a single 600 mg dose of ceftaroline as a 1 h intravenous infusion. Blood and CSF samples were collected before and 0.5, 1, 3, 6, 12 and 24 h after the end of the infusion. Concentrations were assayed in plasma and CSF by LC-MS/MS. A two-step compartmental pharmacokinetic analysis was conducted. Ceftaroline plasma data were first analysed, and thereafter plasma parameters estimated and corrected for protein binding of 20% were fixed to fit unbound CSF concentrations. In the final model, parameters for both plasma and CSF data were simultaneously estimated. Nine patients with an EVD were included. The Cmax was 18.29 ± 3.33 mg/L in plasma (total concentrations) and at 0.22 ± 0.17 mg/L in CSF (unbound concentration). The model-estimated CSF input/CSF output clearance ratio was 9.4%, attesting to extensive efflux transport at the blood-CSF barrier. Ceftaroline CSF concentrations are too low to ensure prophylactic protection against most pathogens with MICs between 1 and 2 mg/L, owing to its limited central distribution.


Quality of life following cerebral bypass surgery.
Information available for nurses on counseling cerebral bypass patients regarding the outcomes of surgery is limited. In order to assess the impact of surgery on the patient's quality of life, a questionnaire was mailed to a sample of cerebral bypass patients who were at least three months postoperative and had suffered an ischemic event prior to surgery. Objective and subjective indicators were used to assess quality of life. Objective measures included type and frequency of symptoms most often associated with ischemic events, as well as return to work status. Subjective aspects included an overall assessment of life satisfaction as measured by the Cantril Self Anchoring Scale and satisfaction with these related domains of life: family, social, sex and occupation. Perceptions of body image were also examined. One hundred and two questionnaires were analyzed. Results indicated that for patients who were working before surgery, return to work was significant (p less than .0001). The signs and symptoms most often associated with an ischemic event were identified and overall, the number of reported symptoms was significantly decreased (p less than .0001) after surgery. In addition, an analysis of variance (ANOVA) with repeated measures indicated that patients viewed present and future life as better than life prior to surgery. Patients also reported greater satisfaction with family life (p less than .0001) and body image (p less than .01) following surgery. This information will be useful to nurses in diagnosing and counseling patients with stroke symptoms as well as in developing a comprehensive plan of care for patients who may undergo cerebral bypass surgery.


Photopharmacological Applications for Cherenkov Radiation Generated by Clinically Used Radionuclides.
Translational photopharmacological applications are limited through irradiation by light showing wavelengths within the bio-optical window. To achieve sufficient tissue penetration, using wavelengths >500 nm is mandatory. Nevertheless, the majority of photopharmacological compounds respond to irradiation with more energetic UV light, which shows only a minor depth of tissue penetration in the µm range. Thus, we became interested in UV light containing Cherenkov radiation (CR) induced as a by-product by clinically employed radionuclides labeling specific tissues. Therefore, CR may be applicable in novel photopharmacological approaches. To provide evidence for the hypothesis, we verified the clinically established radionuclides 68Ga and 90Y but not 18F in clinically used activities to be capable of generating CR in aqueous solutions. We then investigated whether the generated CR was able to photoactivate the caged kinase inhibitor cagedAZD5438 as a photoresponsive model system. Herein, 21% uncaging of the model system cagedAZD5438 occurred by incubation with 90Y, along with a non-specific compound decomposition for 68Ga and partly for 90Y. The findings suggest that the combination of a clinically employed radionuclide with an optimized photoresponsive agent could be beneficial for highly focused photopharmacological therapies.


Synthesis and biological properties of tetranuclear ruthenium complexes containing the bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane ligand.
Linear and non-linear tetranuclear ruthenium(ii) complexes containing the bridging ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(ii) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa (P. aeruginosa). The results showed that both tetranuclear complexes had significant antimicrobial activity, with the non-linear (branched) species (Rubb7-TNL) having slightly higher activity than the corresponding linear analogue (Rubb7-TL). The corresponding toxicity against three eukaryotic cell lines - BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (liver carcinoma) - have also been determined. Interestingly, both Rubb7-TNL and Rubb7-TL were as toxic to the eukaryotic cells as they were to the bacteria, a rarity for kinetically-inert cationic polypyridylruthenium(ii) complexes, and exhibited lower IC50 values than cisplatin over 24-, 48- or 72-hour incubation times. Fluorescence spectroscopy was used to study the binding of the ruthenium complexes with human serum albumin (HSA). Rubb7-TNL and Rubb7-TL exhibited strong HSA binding, with equilibrium binding constants in the order of 107 M-1. Confocal microscopy was used to examine the cellular localisation of Rubb7-TNL in BHK cells. The results indicated that the ruthenium complex localised in the nucleolus. Significant accumulation was also observed in the cytoplasm, but not in the mitochondria. Taken together, the results of this study suggest that Rubb7-TNL is an unlikely candidate as an antimicrobial agent, but may have potential as an anticancer drug.


Th17-associated cytokines as a therapeutic target for steroid-insensitive asthma.
Steroid-insensitive asthma is an infrequent but problematic airway disease that presents with persistent symptoms, airflow limitation, or recurrent exacerbations even when treated with steroid-based therapies. Because of unsatisfactory results obtained from currently available therapies for steroid-insensitive asthma, a better understanding of its pathogenesis and the development of new targeted molecular therapies are warranted. Recent studies indicated that levels of interleukin (IL)-17 are increased and both eosinophils and neutrophils infiltrate the airways of severe asthmatics. IL-17 is a proinflammatory cytokine mainly secreted from helper T (Th) 17 cells and is important for the induction of neutrophil recruitment and migration at sites of inflammation. This review focuses on the pathogenetic role of Th17 cells and their associated cytokines in steroid-insensitive asthma and discusses the prospects of novel therapeutic options targeting the Th17 signaling pathway.


The Protective Effect of Resveratrol on Concanavalin-A-Induced Acute Hepatic Injury in Mice.
Pharmacologic Relevance. Resveratrol, an antioxidant derived from grapes, has been reported to modulate the inflammatory process. In this study, we investigated the effects of resveratrol and its mechanism of protection on concanavalin-A- (ConA-) induced liver injury in mice. Materials and Methods. Acute autoimmune hepatitis was induced by ConA (20 mg/kg) in Balb/C mice; mice were treated with resveratrol (10, 20, and 30 mg/kg) daily by oral gavage for fourteen days prior to a single intravenous injection of ConA. Eight hours after injection, histologic grading, proinflammatory cytokine levels, and hedgehog pathway activity were determined. Results. After ConA injection, the cytokines IL-2, IL-6, and TNF-α were increased, and Sonic hedgehog (Shh), Glioblastoma- (Gli-) 1, and Patched (Ptc) levels significantly increased. Pretreatment with resveratrol ameliorated the pathologic effects of ConA-induced autoimmune hepatitis and significantly inhibited IL-2, IL-6, TNF-α, Shh, Gli-1, and Ptc. The effects of resveratrol on the hedgehog pathway were studied by western blotting and immunohistochemistry. Resveratrol decreased Shh expression, possibly by inhibiting Shh expression in order to reduce Gli-1 and Ptc expression. Conclusion. Resveratrol protects against ConA-induced autoimmune hepatitis by decreasing cytokines expression in mice. The decreases seen in Gli-1 and Ptc may correlate with the amelioration of hedgehog pathway activity.


[A man who is not able to straighten his knee].
An 86-year-old man presented at the Emergency Department with pain in his right leg and the inability to extend his knee after a fall. An ultrasound of the leg revealed a quadriceps tendon rupture. Surgical repair was performed and we expect complete recovery.


Influence of antenatal glucocorticoid on preterm lamb diaphragm.
BackgroundPregnant women at a high risk of preterm delivery receive glucocorticoids to accelerate fetal lung maturation and surfactant synthesis. However, the effect of antenatal steroids on the developing diaphragm remains unclear. We hypothesized that maternal betamethasone impairs the fetal diaphragm, and the magnitude of the detrimental effect increases with longer duration of exposure. We aimed to determine how different durations of fetal exposure to maternal betamethasone treatment influence the fetal diaphragm at the functional and molecular levels.MethodsDate-mated merino ewes received intramuscular injections of saline (control) or two doses of betamethasone (5.7 mg) at an interval of 24 h commencing either 2 or 14 days before delivery. Preterm lambs were killed after cesarean delivery at 121-day gestational age. In vitro contractile measurements were performed on the right hemidiaphragm, whereas molecular/cellular analyses used the left costal diaphragm.ResultsDifferent durations of fetal exposure to maternal betamethasone had no consistent effect on the protein metabolic pathway, expression of glucocorticoid receptor and its target genes, cellular oxidative status, or contractile properties of the fetal lamb diaphragm.ConclusionThese data suggest that the potential benefits of betamethasone exposure on preterm respiratory function are not compromised by impaired diaphragm function after low-dose maternal intramuscular glucocorticoid exposure.


Depolarization without calcium can release gamma-aminobutyric acid from a retinal neuron.
Calcium influx is often an essential intermediate step for the release of neurotransmitter. However, some retinal neurons appear to release transmitter by a mechanism that does not require calcium influx. It was uncertain whether depolarization released calcium from an intracellular store or released transmitter by a mechanism that does not require calcium. The possibility that voltage, and not calcium, can regulate the release of transmitter was studied with pairs of solitary retinal neurons. Horizontal and bipolar cells were isolated from fish retinas and juxtaposed in culture. Communication between them was studied with electrophysiological methods. A horizontal cell released its neurotransmitter, gamma-aminobutyric acid, when depolarized during conditions that buffered the internal calcium concentration and prohibited calcium entry. The speed and amount of material released were sufficient for a contribution to synaptic transmission.


Temperature Regulation of Primary and Secondary Seed Dormancy in Rosa canina L.: Findings from Proteomic Analysis.
Temperature is a key environmental factor restricting seed germination. Rose (Rosa canina L.) seeds are characterized by physical/physiological dormancy, which is broken during warm, followed by cold stratification. Exposing pretreated seeds to 20 °C resulted in the induction of secondary dormancy. The aim of this study was to identify and functionally characterize the proteins associated with dormancy control of rose seeds. Proteins from primary dormant, after warm and cold stratification (nondormant), and secondary dormant seeds were analyzed using 2-D electrophoresis. Proteins that varied in abundance were identified by mass spectrometry. Results showed that cold stratifications affected the variability of the highest number of spots, and there were more common spots with secondary dormancy than with warm stratification. The increase of mitochondrial proteins and actin during dormancy breaking suggests changes in cell functioning and seed preparation to germination. Secondary dormant seeds were characterized by low levels of legumin, metabolic enzymes, and actin, suggesting the consumption of storage materials, a decrease in metabolic activity, and cell elongation. Breaking the dormancy of rose seeds increased the abundance of cellular and metabolic proteins that promote germination. Induction of secondary dormancy caused a decrease in these proteins and germination arrest.


Physical mapping of the evolutionary boundary between human chromosomes 21 and 22 on mouse chromosome 10.
Adjacent regions of mouse Chromosome 10 (MMU10) show conserved synteny with human chromosome 22 (HSA22) and the telomeric region of HSA21. Physical mapping on MMU10 using YAC fragmentation and PAC contig analyses demonstrates that Prmt2 has a position consistent with its human homolog, HRMT1L1, being telomeric to S100B on HSA21. This result establishes Prmt2 as the new proximal boundary of the region of conserved synteny between MMU10 and HSA21 and predicts that it is the most telomeric gene known on HSA21. Physical mapping refines the positions and order of HSA22 homologs Mmp11, Mif, and Ddt, demonstrates the orientation of S100b on the mouse chromosome, and localizes the junction of conserved synteny between HSA21 and HSA22 on MMU10. Comparative mapping in this region is important for defining gene structure and dosage imbalance in Down syndrome (DS), for developing animal models of DS, and for understanding processes of chromosome evolution.


"I'm at breaking point"; Exploring pharmacists' resilience, coping and burnout during the COVID-19 pandemic.
There is a lack of evidence on how the multimodal dynamic process of resilience has impacted personal adaptation of frontline healthcare professionals, working under extreme pressure during the COVID-19 global pandemic. To explore resilience, burnout and wellbeing for UK pharmacists in patient-facing roles, including individual and organisational factors that align to the ABC-X theoretical model of the dynamic process of resilience. A non-experimental pragmatist research design was adopted, with a cross-sectional online survey distributed via social media and professional networks between June and July 2020. Quantitative data aligned to a positivist research paradigm was collected using validated scores, to statistically analyse wellbeing, burnout and resilience. Qualitative textual data, consistent with an interpretivist research paradigm, were analysed following an inductive thematic approach. A total of 199 surveys from pharmacists working within community, hospital and GP sectors were analysed. Wellbeing scores were strongly correlated to resilience scores. Wellbeing and resilience scores were both inversely correlated with burnout scores. Two-thirds of participants were classified as high-risk within the burnout scales.Key stressors were highlighted by participants, who described how individual resources and perceptions shaped their experience, which overall contributed to their burnout. Organisations that supported pharmacists embraced change and quickly adopted new ways of working, such as teleconsultations, flexible and remote working, redesign of workflow, alongside clear guidance. However, there was also reported frustration at lack of, slow or conflicting guidance from employers. This study adds to the growing evidence base for how individuals are affected by adverse events in a dynamic environment, alongside the role that employers can play in supporting individual and organisational resilience. It provides an opportunity to learn from pharmacists' responses to the COVID-19 pandemic, and a call to action for healthcare organisations to rebuild and invest resources into sustained support for staff wellbeing.


Rectal atresia and rectal stenosis: the ARM-Net Consortium experience.
To assess the number, characteristics, and functional short-, and midterm outcomes of patients with rectal atresia (RA) and stenosis (RS) in the ARM-Net registry. Patients with RA/RS were retrieved from the ARM-Net registry. Patient characteristics, associated anomalies, surgical approach, and functional bowel outcomes at 1 and 5-year follow-up were assessed. The ARM-Net registry included 2619 patients, of whom 36 (1.3%) had RA/RS. Median age at follow-up was 7.0 years (IQR 2.3-9.0). Twenty-three patients (63.9%, RA n = 13, RS n = 10) had additional anomalies. PSARP was the most performed reconstructive surgery for both RA (n = 9) and RS (n = 6) patients. At 1-year follow-up, 11/24 patients with known data (45.8%, RA n = 5, RS n = 6) were constipated, of whom 9 required stool softeners and/or laxatives. At 5-year follow-up, 8/9 patients with known data (88.9%, RA n = 4, RS n = 4) were constipated, all requiring laxatives and/or enema. RA and RS are rare types of ARM, representing 1.3% of patients in the ARM-Net registry. Additional anomalies were present in majority of patients. Different surgical approaches were performed as reconstructive treatment, with constipation occurring in 46% and 89% of the patients at 1 and 5-year follow-up. However, accurate evaluation of long-term functional outcomes remains challenging.


[PREVALENCE AND ASSOCIATED FACTORS OF HUMAN SCABIES IN PRISONS IN DOSSO, NIGER].
Scabies is a contagious, pruritic, cosmopolitan dermatosis, widespread especially in human communities, due to parasitism by a mite Sarcoptes scabiei var hominis A lack of hygiene and overcrowding inside the houses are favourable factors. The aim of our study was to determine the prevalence and factors associated with the occurrence of human scabies in the prison environment in Dosso (Niger). Prospective descriptive cross-sectional study conducted in November 2022 in the civil prison of Dosso on authorization of the prison administration. The collected data were sociodemographic characteristics, personal history of pruritus and its characteristics, risk factors related to hygiene and conditions of incarceration, examination performed by a dermatologist to look for clinical signs of scabies. The diagnosis was retained in any inmate presenting one or more elements at the interrogation and at the physical examination. Out of a total of 352 inmates, 43 (38 males and 5 females) had scabies, a prevalence of 12%. The average age was 33 with extremes of 18 and 62 years. Of the scabies patients, 9% reported a history of intense, sleepless pruritus prior to incarceration. Most of the inmates, 86%, were in cells with more than 20 inmates. Among those with scabies, 42% showered twice a day, 81% changed clothes after showering and 74% used soap regularly for washing. The topography of the lesions was external genitalia (37%), buttocks (21%), inner thighs (16%), interdigital spaces (9%), elbows (9%) and wrists (7%). The inmates were informed about the disease, treatment information was explained to them, and they attended a session on hygiene promotion. All cases of scabies detected were prescribed a local treatment based on benzyl benzoate lotion 25%. Human scabies is common in the prison environment in Dosso. Too often, scabies goes undetected and is confused with other pruritic dermatoses, such as eczema or atopic dermatitis. Prison medical staff should be trained in scabies in order to prevent scabies outbreaks. The authorities in the region should make the improvement of hygiene and detention conditions in prisons their priority.


Evaluation of the Retrogasserian Opioid Application in the Treatment of Idiopathic Trigeminal Neuralgia.
To evaluate the clinical outcomes of the retrogasserian opioid application in patients with type 1 trigeminal neuralgia. A total of 37 patients (12 male, 25 female; average age 56.2 ± 5.4 years) who were administered retrogasserian opioid due to type 1 trigeminal neuralgia between February 2012 and May 2015 were included in the study. A visual analogue scale was used to evaluate pain at the last preoperative and postoperative visits (median follow-up period: 13 months, mean follow-up period: 15.6 months). All parameters were analysed using Wilcoxon signed-rank and Mann-Whitney U tests, with p < 0.05 considered statistically significant. Visual analogue scale scores of all 37 patients were significantly improved in the postoperative period. The average visual analogue scale scores were 7.9 ± 0.62 preoperatively and 2.9 ± 0.5 postoperatively. All changes were statistically significant. Percutaneous retrogasserian opioid injection in type 1 trigeminal neuralgia is an effective and safe method of pain control.


A protein switch sensing system for the quantification of sulfate.
Protein engineering has generated versatile methods and technologies that have been instrumental in advancements in the fields of sensing, therapeutics, and diagnostics. Herein, we demonstrate the employment of rational design to engineer a unique bioluminescence-based protein switch. A fusion protein switch combines two totally unrelated proteins, with distinct characteristics, in a manner such that the function of one protein is dependent on another. Herein we report a protein switch sensing system by insertion of the sulfate-binding protein (SBP) into the structure of the photoprotein aequorin (AEQ). In the presence of sulfate, SBP undergoes a conformational change bringing the two segments of AEQ together, "turning on" bioluminescence in a dose-dependent fashion, thus allowing quantitative detection of sulfate. A calibration plot was obtained by correlating the amount of bioluminescence generated with the concentration of sulfate present. The switch demonstrated selectivity and reproducibility, and a detection limit of 1.6×10(-4)M for sulfate. Moreover, the sensing system was validated by performing sulfate detection in clinical and environmental samples, such as, serum, urine, and tap water. The detection limits and working ranges in all three samples fall within the average normal/recommended sulfate levels in the respective matrices.