Differential stoichiometric responses of shrubs and grasses to increased precipitation in a degraded karst ecosystem in Southwestern China.
The elemental concentrations of both plants and soils are sensitive to variations in precipitation due to the limiting roles of water on soil processes and plant growth in karst ecosystems of Southwestern China; however, precipitation is predicted to increase in this region. Nevertheless, it is unclear how the elemental composition of soils and plants might respond to such increases in moisture. Particularly, how potassium (K) may behave as a key mediator in the regulation of the water potential of plants. For this study, the responses of the elemental composition of both soils and plants to the variable addition of water were investigated. Two grasses (Cymbopogon distans and Arundinella setosa) and two shrubs (Carissa spinarum and Bauhinia brachycarpa) were investigated under four levels of watering treatments 0%, +20%, +40%, and +60%, relative to the annual rainfall, respectively. Compared to the control (CK), the soil water content (SWC) increased to 3.75, 3.86, and 4.34 mg g-1 in T1, T2, and T3 groups, respectively (p < 0.05). Non-metal elements (C, H, N, S, and P, except for Si) in the soil were relatively stable with water addition; however, metal elements (Al, Na, Mg, Fe, and K, along with Si) increased significantly, whereas Zn and Ca decreased (p < 0.05). With water addition, leaf N and P remained unchanged in all four species, while K, Mg, and S decreased in both shrubs (higher C:K, N:K, and P:K). Increases in Fe, Si, and K were observed in both grasses (lower C:K, N:K, and P:K), which suggested that K played distinct roles for water regulation in shrubs and grasses. These findings implied that the elemental compositions of both soils and plants might be altered with increasing precipitation in the future, where different plant types may adopt distinct K-regulation strategies to cope with variable soil moisture.


A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice.
Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca(2+) permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia.


An antiserum against 9-deoxy-6,9-epoxy-PGF1alpha recognizes and binds PGI2 (prostacyclin).
Antibodies were prepared against 9-deoxy-6,9-epoxy-PGF1alpha, the 5,6-dihydro analog of prostacyclin (PGI2). By using as the hapten, this structurally similar, stable analog, an antibody population was developed which recognized PGI2 and reversed its influence on platelet aggregation. The antibodies also opposed the normal effect of PGI2 on the cAMP and thromboxane B2 levels during aggregation. By anticipating the cross reaction between the analog and PGI2 and by considering it beneficial, the problem of raising antibodies against an unstable compound has been circumvented.


Mycorrhizal colonisation of mountain birch (Betula pubescens ssp. czerepanovii) along three environmental gradients: does life in harsh environments alter plant-fungal relationships?
Environmental stress affects ectomycorrhizal communities (ECM), but it is not known how general the detected ECM responses are. We investigated ECM fungi on roots of mountain birch, Betula pubescens subsp. czerepanovii (Orlova) Hämet-Ahti, along three environmental gradients, two natural (altitude, seashore) and one human-induced (pollution), within the Kola Peninsula, NW Russia. Chlorophyll fluorescence of birch leaves indicated no environmental stress even in the conditions that were presumed most stressful in terms of abiotic environment, where the biomass and population density of birches were strongly reduced. Although neither overall ECM colonisation nor root fungal biomass showed stress-related patterns, colonisation by Cenococcum geophilum tended to decrease with abiotic stress. ECM morphotype diversity declined with abiotic stress, and along altitudinal gradient this decline was related to an increase in proportion of morphotypes with high fungal biomass. Polycormic birches had higher ECM colonisation than monocormic birches at high stress sites only. ECM morphotype diversity increased with foliar nitrogen concentration at low stress sites, but not at high stress sites. Birches with higher chlorophyll fluorescence had lower chitin concentration in their roots (indicating lower proportion of fungal structures) at high stress sites only. Our results suggest that at high stress sites (1) mechanical shelter created by polycormic trees may favour ECM fungi and (2) mountain birches maintain lower ECM diversity than at low stress sites.


Sinus node dysfunction associated with absence of right superior vena cava.
A 41-year-old man presented with dizziness associated with sinus bradycardia and sinus arrest. An attempt to implant a transvenous pacing lead was frustrated by absence of the right superior vena cava. The left superior vena cava persisted and drained via the coronary sinus into the right atrium. Absence of the right superior vena cava may present with symptomatic sinus node dysfunction and may require an epicardial demand pacing system.


Slowly-adapting type II afferents contribute to conscious touch sensation in humans: Evidence from single unit intraneural microstimulation.
Slowly-adapting type II (SA-II, Ruffini) mechanoreceptive afferents respond well to pressure and stretch, and are regularly encountered in human microneurography studies. Despite an understanding of SA-II response properties, their role in touch perception remains unclear. Specific roles of different myelinated Aβ mechanoreceptive afferents in tactile perception have been revealed using single unit intraneural microstimulation (INMS), via microneurography, recording from and then electrically stimulating individual afferents. This method directly links single afferent artificial activation to perception, where INMS produces specific 'quantal' touch percepts associated with different mechanoreceptive afferent types. However, SA-II afferent stimulation has been ambiguous, producing inconsistent, vague sensations, or no clear percept. We physiologically characterized hundreds of individual Aβ mechanoreceptive afferents in the glabrous hand skin and examined the subsequent percepts evoked by trains of low amplitude INMS current pulses (<10 μA). We present 18 SA-II afferents where INMS resulted in a clear, electrically evoked sensation of large (∼36 mm2 ) diffuse pressure, which was projected precisely to their physiologically-defined receptive field in the skin. This sensation was felt as natural, distinctive from other afferents, and showed no indications of multi-afferent stimulation. Stimulus frequency modulated sensation intensity and even brief stimuli (4 pulses, 60 ms) were perceived. These results suggest that SA-II afferents contribute to perceived tactile sensations, can signal this rapidly and precisely, and are relevant and important for computational models of touch sensation and artificial prosthetic feedback. KEY POINTS: Slowly adapting type II mechanoreceptors (SA-IIs) are primary sensory neurons in humans that respond to pressure and stretch applied to the skin. To date, no specific conscious correlate of touch has been linked to SA-II activation. Using microneurography and intraneural microstimulation to stimulate single sensory neurons in human subjects, we find a specific sensation linked to the activation of single SA-II afferents. This sensation of touch was reported as gentle pressure and subjects could detect this with a high degree of accuracy. Methods of artificial tactile sensory feedback and computational models of touch should include SA-IIs as meaningful contributors to the conscious sensation of touch.


Delayed intrapleural migration of a ventriculoperitoneal shunt.
We report a case of delayed intrapleural migration of the peritoneal catheter of a ventriculoperitoneal shunt. This is an unusual but life-threatening complication of peritoneal shunting for the treatment of hydrocephalus. A method of treatment and abbreviated review of shunt complications is included.


Can the impact of micro- and nanoplastics on human health really be assessed using in vitro models? A review of methodological issues.
Because of the many advantages they offer (strength, low cost, durability, lightweight, resistance, etc.), plastics are integral part of our daily life with a production constantly rising. However, their waste management is still inadequate, resulting in their release and accumulation in the environment, representing a main source of pollution. Their degradation results in debris of variable size including microplastics (0.1 μm-5 mm) and even nanoplastics (<0.1 μm), whose potential impact on ecosystems and human health have raised concerns. The potential adverse effects they may cause have been evaluated using both in vitro and in vivo models. However, due to some specific characteristics of micro- and nanoplastics, there are challenging questions about whether conventional in vitro tests are appropriate for evaluating their toxicity. For example, low-density plastics float on the surface of the culture medium and cannot come into contact with cells adhering to the bottom of the culture plates, which prevents proper evaluation of potential adverse effects and leads to misinterpretation of toxicological assays. In this review, we discuss the main issues related to the evaluation of micro- and nanoplastics toxicity using conventional in vitro assays. A literature survey has allowed to propose some solutions to circumvent these issues including the use of mathematical models to accurately determine the dose of particles delivered to cells, advanced 3D models (organoids), inverted cell culture models, cell cultures at the air-liquid interface or under dynamic conditions. Finally, we propose some perspectives and recommendations for further research on the in vitro evaluation of micro- and nanoplastics toxicity, underlining the importance of using standardized protocols for comparison purposes and samples and experimental conditions more representative of real-life exposure.


Sequence-specific [1H]NMR resonance assignments and secondary structure identification for 1- and 2-zinc finger constructs from SW15. A hydrophobic core involving four invariant residues.
Complete [1H]NMR resonance assignments are presented for the second of the three zinc fingers from SW15 as it appears in both 1- and 2-finger constructs. Signals from finger 2 are unaffected by the presence or absence of finger 1, showing that the protein has a modular construction. The structure of finger 2 comprises a helix running from N56 to Q67, and a region approximating to an anti-parallel beta-sheet running from Y42 to F53. These features combine to produce a hydrophobic core in the structure involving the invariant residues Y42, F53, L59 and H62.


Are physicians ready for precision antibiotic prescribing? A qualitative analysis of the acceptance of artificial intelligence-enabled clinical decision support systems in India and Singapore.
Artificial intelligence (AI)-driven clinical decision support systems (CDSSs) can augment antibiotic decision-making capabilities, but physicians' hesitancy in adopting them may undermine their utility. We conducted a cross-country comparison of physician perceptions on the barriers and facilitators in accepting an AI-enabled CDSS for antibiotic prescribing. We conducted in-depth interviews with physicians from the National Centre for Infectious Diseases (NCID), Singapore, and Christian Medical College Vellore (CMCV), India, between April and December 2022. Our semi-structured in-depth interview guides were anchored on Venkatesh's UTAUT model. We used clinical vignettes to illustrate the application of AI in clinical decision support for antibiotic prescribing and explore medico-legal concerns. Most NCID physicians felt that an AI-enabled CDSS could facilitate antibiotic prescribing, while most CMCV physicians were sceptical about the tool's utility. The hesitancy in adopting an AI-enabled CDSS stems from concerns about the lack of validated and successful examples, fear of losing autonomy and clinical skills, difficulty of use, and impediment in work efficiency. Physicians from both sites felt that a user-friendly interface, integration with workflow, transparency of output, a guiding medico-legal framework, and training and technical support would improve the uptake of an AI-enabled CDSS. In conclusion, the acceptance of AI-enabled CDSSs depends on the physician's confidence with the tool's recommendations, perceived ease of use, familiarity with AI, the organisation's digital culture and support, and the presence of medico-legal governance of AI. Progressive implementation and continuous feedback are essential to allay scepticism around the utility of AI-enabled CDSSs.


Timing and duration of use of GnRH antagonist down-regulation for IVF/ICSI cycles have no impact on oocyte quality or pregnancy outcomes.
To evaluate whether oocyte quality, implantation and pregnancy outcomes in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) are related to the duration of gonadotropin-releasing hormone (GnRH)-antagonist use or the timing of its initiation. Retrospective cohort study of 178 conventional IVF/ICSI cycles. All patients underwent ovarian stimulation with gonadotropins and GnRH-antagonist for pituitary down-regulation. Spearman correlations and logistic regression were used for statistical analysis. There was no correlation between the duration of use or the timing of initiation of GnRH-antagonist with oocyte quality or implantation and pregnancy outcomes. Oocyte quality was influenced by the peak estradiol. Implantation was influenced by the patient's age. Early pregnancy loss, by the endometrial thickness on human chorionic gonadotropin-day. Ongoing pregnancy was independent from the variables evaluated. GnRH-antagonist duration of use or starting day did not influence oocyte quality, implantation rates, and pregnancy rates. We hypothesize that a follicle stimulating hormone/luteinizing hormone dose increase when antagonist was started, may have had an impact on our findings.


Avian pathogenic Escherichia coli transmission from broiler breeders to their progeny in an integrated poultry production chain.
Early cases of colibacillosis with omphalitis, yolk sac infection and increased mortality were observed in five broiler chicken flocks (A1, A2, A3, A4 and B1) from two broiler breeder flocks A and B, respectively. Avian pathogenic Escherichia Coli (APEC) serotype O78, Fim/Tsh/Iuc pathotype, were isolated from flocks A, A1, A2, A3 and A4, and APEC serotype O139, pathotype Fim/Iuc, from flocks B and B1. APEC O78 strains isolated from broiler chicks A1, A2, A3 and A4, originating from breeder flock A, had the same antibiotic resistance pattern as APEC O139 strains isolated from broiler chicks B1 and breeder B. The random amplified polymorphic DNA technique performed on APEC strains revealed two distinct clusters of genetic similarity: cluster I consisted of some APEC O78 and cluster II of APEC O139. These results indicated that a transmission of APEC strains from adults A and B to their respective progeny could occur.


Expression of capsule-associated genes of Cryptococcus neoformans.
Cryptococcus neoformans produces an extracellular polysaccharide capsule that is related to its virulence. The production of capsular components was reported to be accelerated when cultured on media with lower amount of glucose. In this study, relationship between capsule synthesis and expression of capsule-associated genes (CAP genes) was investigated by quantitative real-time PCR analysis. Normally encapsulated strains and a stable acapsular strain were cultured in 1% polypepton medium with 0.1% or 15% glucose. The results of assessment of the capsule size showed that the capsule of yeast cells cultured in the medium with low amount of glucose was thicker than that with high amount of glucose. The CAP gene expressions of normally encapsulated strains were higher in the medium with 0.1% glucose than in the medium with 15% glucose. Furthermore, CAP10, CAP59 and CAP60 genes were expressed very low in a stable acapsular strain, and CAP64 gene was not expressed. Results of assessment of capsule size and CAP gene expressions by quantitative real-time PCR analysis indicated that CAP gene expressions might be related to the production of capsule, and that glucose concentration in culture media might be related to the expression of CAP genes.


Association Between Dietary Fatty Acid Pattern and Risk of Oral Cancer.
To investigate the association between dietary fatty acid (FA) patterns and the risk of oral cancer. A case-control study which included 446 patients with oral cancer and 448 controls subjects was conducted in Southeast China. A structured food frequency questionnaire was used to assess the dietary FA consumption before cancer diagnosis. FA patterns were identified using the principal component analysis, and the relationship between the dietary FA patterns and oral cancer was analyzed by logistic regression. General differences in FA intake were observed between the patient and control groups. The intakes of saturated FAs (SFAs) C14:0, C16:0, C18:0, and monounsaturated FA C18:1 were higher in the patient group than the control group (p < 0.001). Four FA patterns were derived by principal component analysis. The "SFA" pattern, "Polyunsaturated FA" pattern, "Monounsaturated FA" pattern, and "Medium- and long-chain FA" pattern, which could explain 75.7% of the variance of the dietary FA intake, were submitted to logistic regression analysis. A positive association was observed between the "SFA" pattern and oral cancer risk. Compared with the lowest quartile score, the OR of the highest quartile score was 3.71 (95%CI: 2.31, 5.94, P trend < 0.001) in the multivariate logistic regression model. No significant association was found among the other three patterns and oral cancer risk. General differences in dietary FA intake were observed between patients with oral cancer and controls. A positive association between the "SFA" pattern and risk of oral cancer was observed after adjusting for potential confounders.


An immunochemical procedure for the purification of rat class I antigens (RT1.A/RT1.E) from detergent-solubilized erythrocytes.
An immunochemical procedure using two immunoaffinity columns for the isolation of rat Class I antigens from detergent-solubilized DA erythrocytes is described. The protocol yields a pure Class I preparation as assessed by silver staining of sodium dodecyl sulfate-polyacrylamide gels and comparison of the amino acid composition with that previously determined for H-2K/D. The antigen preparation is capable of specifically blocking the hemagglutination of DA erythrocytes by Class I-specific alloantiserum.


Exposure to hydrocarbon concentrations while commuting or exercising in Dublin.
In Ireland, several studies have monitored the air pollution due to traffic in both urban and rural environments. However, few studies have attempted to quantify the relative exposure to traffic derived HC pollutants between different modes of commuter transport. In this study, the difference in pollution exposure between bus and cycling commuters on a route in Dublin was compared by sampling for five vehicle related hydrocarbons: benzene, 1,3-butadiene, acetylene, ethane and ethylene. Samples were collected during both morning and afternoon rush hour periods using a fixed speed pump to gain representative concentrations across the whole journey. Journey times were also measured, as were typical breathing rates in order to calculate the overall dose of pollutant inhaled on the journey. Results clearly picked up significantly higher pollutant concentrations in the bus compared to cycling and also revealed elevated concentrations on the congested side of the road compared to the side moving against the traffic. However, when respiration rates and travel times were taken into account to reveal the mass of pollutants inhaled over the course of a journey, the pattern was reversed, showing slightly enhanced levels of hydrocarbons for the cyclist compared to the bus passenger. In addition, the concentrations of these compounds (excluding ethane), were ascertained at playing pitches in the vicinity of a heavily trafficked suburban motorway and in Dublin city centre. Although the concentrations were relatively low at all sites, when breathing rates were taken into consideration, the average inhaled weights of pollutants were, on occasion, higher than those average values observed for both bus and bicycle commuters.


Clinical significance of potential pathogenic microorganisms of sputum in patients with pulmonary tuberculosis.
Bacterial culture of sputum is frequently positive in patients with pulmonary tuberculosis (TB). However, it remains to be clarified whether detection of potential pathogenic microorganisms (PPM) in sputum represents bacterial infection or only colonization of the respiratory tract. In the present study, we investigated the clinical significance of PPM in patients with pulmonary TB. Sputum culture for PPM was studied in 174 pulmonary TB patients (117 males and 57 females, mean age of 71 years) on the day of admission. Ninety-seven patients (63 males and 34 females, mean age of 67.1 years) also underwent transtracheal aspirates (TTA). Quantitative culture of sputum and TTA was performed to distinguish infection from colonization. The results were evaluated as follows: more than 106 or 105 c.f.u./mL indicated infection in the case of sputum or TTA samples, respectively. We also compared various clinical parameters between patients with PPM and patients with non-potential pathogenic microorganisms (non-PPM). Potential pathogenic microorganisms were positive in 44% and 24% of sputum and TTA specimens, respectively. However, quantitative culture for PPM showed positive findings in only 11% and 3% of sputum and TTA specimens, respectively. A comparative study of the clinical features revealed that PPM patients had a lower bodyweight and lower serum albumin levels than non-PPM patients. A fatal outcome was also more common in PPM patients than in non-PPM patients. Logistic regression analysis further confirmed that PPM clearly contributed to a fatal outcome in addition to the previously established parameters including age, performance status, haemoglobin, albumin and radiographic disease extent. Although sputum PPM represent only colonization of the upper respiratory tract in TB patients, they are associated with a poor prognosis.


Liver resection for metastatic gastric cancer.
Liver resection represents a curative treatment approach in patients suffering from liver metastases from gastric cancer. However, its value in the treatment of these patients remains controversial. This study was conducted to evaluate the safety and effectiveness of liver resection in these conditions and to identify criteria for the selection of suitable patients. From January 1988 to December 2002, 24 patients underwent liver resection for metastatic gastric cancer. The outcome of these 24 patients was retrospectively reviewed using a prospective database. Patient, tumour and operative parameters were analyzed for their influence on long-term survival. One patient died and four patients (17%) developed complications during the postoperative course. The overall one-, three- and five-year survival was 38%, 16% and 10%, respectively. After curative resection (n=17), the one-, three- and five-year survival rate was 53%, 22% and 15%, respectively, and patients with metachronous metastases restricted to the liver (n=5) had a one-, three- and five-year survival of 80%, 40% and 40%, respectively. In the univariate analysis, extrahepatic manifestation showed in tendency (p=0.069) and resection margins statistically significant (p=0.005) influence on survival. The multivariate analysis revealed only resection margins as an independent prognostic factor for survival. Long-term survival can be achieved by liver resection in well selected patients and may be considered in the multidisciplinary treatment approach of metastatic gastric cancer. Patients with metastatic disease restricted to the liver in whom a curative resection can be achieved seem to be most suitable for liver resection.


Extracellular pH mapping of liver cancer on a clinical 3T MRI scanner.
To demonstrate feasibility of developing a noninvasive extracellular pH (pHe ) mapping method on a clinical MRI scanner for molecular imaging of liver cancer. In vivo pHe mapping has been demonstrated on preclinical scanners (e.g., 9.4T, 11.7T) with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), where the pHe readout by 3D chemical shift imaging (CSI) depends on hyperfine shifts emanating from paramagnetic macrocyclic chelates like TmDOTP5- which upon extravasation from blood resides in the extracellular space. We implemented BIRDS-based pHe mapping on a clinical 3T Siemens scanner, where typically diamagnetic 1 H signals are detected using millisecond-long radiofrequency (RF) pulses, and 1 H shifts span over ±10 ppm with long transverse (T2 , 102 ms) and longitudinal (T1 , 103 ms) relaxation times. We modified this 3D-CSI method for ultra-fast acquisition with microsecond-long RF pulses, because even at 3T the paramagnetic 1 H shifts of TmDOTP5- have millisecond-long T2 and T1 and ultra-wide chemical shifts (±200 ppm) as previously observed in ultra-high magnetic fields. We validated BIRDS-based pH in vitro with a pH electrode. We measured pHe in a rabbit model for liver cancer using VX2 tumors, which are highly vascularized and hyperglycolytic. Compared to intratumoral pHe (6.8 ± 0.1; P < 10-9 ) and tumor's edge pHe (6.9 ± 0.1; P < 10-7 ), liver parenchyma pHe was significantly higher (7.2 ± 0.1). Tumor localization was confirmed with histopathological markers of necrosis (hematoxylin and eosin), glucose uptake (glucose transporter 1), and tissue acidosis (lysosome-associated membrane protein 2). This work demonstrates feasibility and potential clinical translatability of high-resolution pHe mapping to monitor tumor aggressiveness and therapeutic outcome, all to improve personalized cancer treatment planning.


The effect of various resuscitative regimens on hemorrhagic shock in puppies.
Since shock secondary to hemorrhage is not infrequently encountered in the pediatric patient, a puppy model was devised to help measure and monitor cardiovascular and metabolic changes that occur before and after resuscitation from hypovolemic shock (mean arterial pressure of 50 mm Hg for 1 hr). Three resuscitation protocols were compared: whole blood (replacement:shed) 1:1, 5% albumin in Ringer's lactate 1:1; and Ringer's lactate 3:1. All dogs survived the experiment and responded similarly during the shock period. Thermal dilution cardiac output rose in all groups after resuscitation; however, in the Ringer's lactate and 5% albumin groups, cardiac output was statistically greater than that observed in the blood group. In all groups, pH and blood pressure approached but did not return completely to baseline levels after resuscitation. In addition, early resuscitation demonstrated a further decrease pH ("hidden acidosis") before it began to return toward normal as resuscitation progressed. This study suggests that the infusion of large volumes of Ringer's lactate or 5% albumin in Ringer's lactate are equally efficacious in the treatment of hemorrhage. However, 5% albumin seems to be preferable because it allows infusion of a smaller quantity of electrolyte solution with equivalent physiologic benefits.


Benthic foraminiferal assemblages and trace metals reveal the environment outside the Pearl River Estuary.
We investigated the distribution patterns of the benthic foraminiferal assemblages outside the Pearl River Estuary in relation to trace metals, organic carbon and sedimentary particle fractions. The study area is unpolluted to moderately polluted by Cr, Cu, Pb and Zn and is completely polluted by Ni. The highest levels are found in the western coastal zone. Spatial distributions of the measured elements are strongly related to the behavior of the sedimentary clay fraction. The analyses of species abundance and community diversity as well as subsequent canonical correspondence analysis were used to reveal the relationship between foraminifera data and environmental parameters. Four sampling site groups established by factor analysis were distributed from the coastal area to the inner shelf. Their distribution patterns have a strong correlation with Cu, Pb and Ba. This research shows that benthic foraminifera can be used as bioindicators of trace metal pollutants outside the Pearl River Estuary.


Corrigendum: Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation through the Inhibition of STAT3/YKL-40 Axis in Mice with Chronic Cerebral Hypoperfusion-Induced White Matter Lesions.
[This corrects the article DOI: 10.3389/fimmu.2022.841290.].


Biomechanical properties of an advanced new carbon/flax/epoxy composite material for bone plate applications.
This work is part of an ongoing program to develop a new carbon fiber/flax/epoxy (CF/flax/epoxy) hybrid composite material for use as an orthopaedic long bone fracture plate, instead of a metal plate. The purpose of this study was to evaluate the mechanical properties of this new novel composite material. The composite material had a "sandwich structure", in which two thin sheets of CF/epoxy were attached to each outer surface of the flax/epoxy core, which resulted in a unique structure compared to other composite plates for bone plate applications. Mechanical properties were determined using tension, three-point bending, and Rockwell hardness tests. Also, scanning electron microscopy (SEM) was used to characterize the failure mechanism of specimens in tension and three-point bending tests. The results of mechanical tests revealed a considerably high ultimate strength in both tension (399.8MPa) and flexural loading (510.6MPa), with a higher elastic modulus in bending tests (57.4GPa) compared to tension tests (41.7GPa). The composite material experienced brittle catastrophic failure in both tension and bending tests. The SEM images, consistent with brittle failure, showed mostly fiber breakage and fiber pull-out at the fractured surfaces with perfect bonding at carbon fibers and flax plies. Compared to clinically-used orthopaedic metal plates, current CF/flax/epoxy results were closer to human cortical bone, making the material a potential candidate for use in long bone fracture fixation.


How Children and Adults Encode Causative Events Cross-Linguistically: Implications for Language Production and Attention.
This study investigates the implications of language-specific constraints on linguistic event encoding for the description and on-line inspection of causative events. English-speaking and Greek-speaking adults, 3-year-olds, and 4-year-olds viewed and described causative events, which are composed of Means and Result subevents, in an eyetracking study. The results demonstrate cross-linguistic differences in the informational content of causative event descriptions: Greek speakers across age groups were more likely than English speakers to mention only one causative subevent. Developmental changes in the tendency to encode information about causative events in language were also evident: in both language groups, adults were more likely than children to mention both Means and Result subevents. Finally, for both adult and child speakers of both languages, preparing different types of event descriptions changed the way that events were visually inspected, shifting attention toward to-be-encoded subevents. These findings offer some of the first evidence about the development of the language production system, the attentional mechanisms that it employs, and its workings in speakers of different languages.


Factors influencing evidence-based practice among undergraduate nursing students: A cross-sectional analysis.
This study aimed to describe the current situation of evidence-based practice (EBP) among undergraduate nursing students in Thailand. A cross-sectional study was conducted. A convenience sample of 470 third- and fourth-year undergraduate nursing students from five public universities across Thailand participated in this study from January 2021 to March 2021. All participants were invited to complete a general information questionnaire, and the Student Evidence-Based Practice Questionnaire (S-EBPQ). The overall mean S-EBPQ score was 5.29 ± 0.71, and the four subscales, from highest to lowest, were attitudes (5.50 ± 0.93), sharing and applying EBP (5.37 ± 0.87), practice (5.18 ± 0.84), and retrieving and reviewing evidence (5.10 ± 0.81). The current situation of S-EBPQ was higher among nursing students who had higher previous EBP studies, familiarity with research methods, confidence in clinical decision-making, preparedness in practice, and access to journals (P < 0.05). This study's findings provide valuable insights for planning strategies that can be integrated into the existing nursing curricula to enhance nursing undergraduates' EBP application in clinical settings.


Magnitude and Composition of Sedentary Behavior in Older Adults Living in a Retirement Community.
High amount of sedentary behavior (SB) has been associated with a multitude of adverse health events in older adults. There are limited data regarding SB in older adults living in retirement communities (RC). This study described the magnitude and composition of SB [non-screen sedentary time (NSST) and screen sedentary time (SST)] in older adults living in a RC and documented variation in this behavior as a function of demographic, health, health behavior and clinical variables. This cross sectional descriptive study enrolled and assessed 100 older males and females living a RC located in the Midwest region of United States. Participants completed a questionnaire for sample characterization and a SB questionnaire. Metric of SB (i.e., TST, NSST and SST) were analyzed overall and separated by the variables of interest. Participants reported on average 10 h/day of sedentary activity (65% on NSST and 35% on SST). Older adults reported to spend most of their awaking hours in activities such as reading, watching TV and computer use. Significant variations on NSST and SST were observed for gender, BMI, perceived health, mobility aid use and number of chronic diseases. These findings may help in the development of tailored strategies and interventions focusing on reducing SB in this particular under-researched subgroup.


Managing anthelmintic resistance--use of a combination anthelmintic and leaving some lambs untreated to slow the development of resistance to ivermectin.
A field study was conducted to test the hypotheses that use of a combination anthelmintic and/or increasing the pool of unselected worms 'in refugia' by leaving a proportion of lambs untreated would slow the development of resistance to ivermectin. Twelve suites of four paddocks (farmlets) were seeded with a mixture of resistant and susceptible isolates of both Trichostrongylus colubriformis and Teladorsagia (Ostertagia) circumcincta calculated to yield a 95% reduction in faecal nematode egg count (FEC) after treatment with ivermectin. Each year for three years the farmlets were stocked in the spring with mobs of lambs which were treated five times at 28-day intervals with either ivermectin or an ivermectin+levamisole combination. In addition, in half the mobs the heaviest 10% of lambs remained untreated at each treatment occasion, resulting in a 2 × 2 factorial treatment structure (i.e. two drench types × two percentage treated) with three complete replicates. The development of resistance to ivermectin, and at the end to levamisole, was measured by larval development assays (LDA) and worm counts from treated and untreated tracer lambs. For T. colubriformis the development of resistance to ivermectin, as measured by tracer lamb worm burdens, was delayed by treatment with the combination and by leaving 10% of lambs untreated. In addition, the interaction between these factors approached significance (p=0.052). Similarly, results of the LDAs indicated a slower development of resistance when lambs were treated with the combination and when 10% of lambs were left untreated. For T. circumcincta, results were compromised by the rapid development of resistance, which appears to be the result of low viability in the field of the susceptible isolate used to contaminate the pastures. Although a small delay in the development of resistance to ivermectin was indicated, this was off-set by an increase in the level of resistance to levamisole. A post-study modelling experiment simulating the conditions of the field study and the starting efficacies for the two nematode species produced equivalent outputs to those measured in the field. Overall, results support the conclusions that use of combination anthelmintics and deliberately increasing 'refugia' of unselected genotypes will slow the development of anthelmintic resistance. However, as indicated in modelling studies, once resistance to all the constituent actives is well developed (efficacy<70%) the value of combinations for slowing the development of resistance is largely lost.


Stability of an epidural analgesic solution containing adrenaline, bupivacaine and fentanyl.
A low dose solution of adrenaline 2 microg x ml(-1), fentanyl 2 microg x ml(-1) and bupivacaine 1 mg x ml(-1) has been reported to give superior pain control when used for epidural analgesia after major surgery. The present paper describes the compounding and chemical stability of this triple-component solution during storage and use. Sterile triple-component concentrates (11X) were diluted by the use of gas isolator technology to give ready-to-use infusion solutions. Eight solutions were analysed by reverse phase high-performance liquid chromatography (HPLC) methods, and assays were performed on 1, 45, 90 and 180 days after storage at 2-8 degrees C. After 180 days the solutions were subsequently stored at 22 degrees C for four days before they were reanalysed. HPLC quantification of adrenaline was also performed on samples from solutions given to 28 different patients. The concentration of adrenaline and fentanyl decreased approximately 3.5% from 1 to 180 days at 4 degrees C and four days at 22 degrees C. The corresponding figure for bupivacaine was an apparent increase by 2.4% in concentration. No absorption to the polypropylene plastic bags of fentanyl and bupivacaine was detected. None of the 28 samples derived from used infusion bags contained less than 95% of the declared content of adrenaline. The triple-component epidural analgesic solution remained stable during six months of cold storage, followed by four days of storage at room temperature. No significant degradation of adrenaline was observed in infusion solutions returned from the wards.


Atrial fibrillation complicating lung cancer resection.
To (1) characterize atrial fibrillation complicating lung cancer resection, (2) evaluate its temporal relationship to other postoperative complications, and (3) assess its economics. From January 1998 to August 2002, 604 patients underwent anatomic lung cancer resection. Atrial fibrillation prevalence, onset, and temporal associations with other postoperative complications were determined. Propensity matching was used to assess economics. Atrial fibrillation occurred in 113 patients (19%), peaking on postoperative day 2. Older age, male gender, heart failure, clamshell incision, and right pneumonectomy were risk factors (P < .01). Although atrial fibrillation was solitary in 75 patients (66%), other postoperative complications occurred in 38. Respiratory and infectious complications were temporally linked with atrial fibrillation onset. In 91 propensity-matched pairs, patients developing atrial fibrillation had more other postoperative complications (30% vs. 9%, P < .0004), had longer postoperative stays (median 8 vs 5 days, P < .0001), incurred higher costs (cost ratio 1.8, 68% confidence limits 1.6-2.1), and had higher in-hospital mortality (8% vs 0%, P = .01). Even when atrial fibrillation was a solitary complication, hospital stay was longer (median 7 vs 5 days, P < .0001), and cost was higher (cost ratio 1.5, 68% confidence limits 1.2-1.6). Atrial fibrillation occurs in 1 in 5 patients after lung cancer resection, with peak onset on postoperative day 2. Risk factors are both patient and procedure related, and atrial fibrillation may herald other serious complications. Although often solitary, atrial fibrillation is associated with longer hospital stay and higher cost. It therefore requires prompt treatment and should stimulate investigation for other problems.


A fully coupled transient excited state model for the sodium channel. I. Conductance in the voltage clamped case.
The behavior under voltage clamp conditions of a coupled kinetic scheme for the sodium channel is examined. The scheme is given diagrammatically by: Numerical simulations are presented which show that this model fits the voltage clamp data which are well described by the Hodgkin-Huxley equations, but also gives the sorts of behavior anomalous to the Hodgkin-Huxley model which have been seen experimentally. Further, straightforward changes in parameter values are shown to be capable of mimicking the ways in which some axonal preparations differ from others. Detailed, but admittedly heuristic, arguments are presented for the propositions that: 1) the model is minimal; i.e. no simpler kinetic model will fit the array of data simulated, and: 2) the transient excited state is necessary; i.e. no model of comparable simplicity with pure voltage dependent kinetics will fit the array of data simulated.


The clinical relevance of posttraumatic avascular necrosis of the humeral head.
Twenty-five patients with a partial or complete collapse of the humeral head caused by post-traumatic avascular necrosis underwent clinical and radiologic evaluation at an average of 7.5 years (range 2.3 to 17.6 years) after having an underlying proximal humeral fracture. Posttraumatic humeral head necrosis was always associated with disability. The overall shoulder function as assessed with the Constant score was 46 points, corresponding to a functional shoulder value of 51% of an age- and sex-matched normal control group. The clinical outcome was significantly related to the anatomic alignment of the fragments of the humerus by the time of healing. In 13 patients (group 1) treatment resulted in an anatomic or nearly anatomic healing of the fracture, and in 12 other patients (group 2) avascular necrosis and collapse ensued in addition to malunion of 1 or more of the fracture fragments. Subjective overall outcome (P < .0001) and pain (P < .0001) were significantly better in group 1. Active anterior elevation averaged 125 degrees in group 1 and 80 degrees in group 2 (P = .0007), and abduction averaged 110 degrees in group 1 and 63 degrees in group 2 (P = .007). The relative shoulder score according to Constant was 65% of an age- and sex-matched normal population for group 1 and 41% for group 2 (P = .001). The results obtained in group 1 were comparable to those reported after hemiarthroplasty for complex humeral fractures. A proximal humeral fracture that is at risk for avascular necrosis has to be reduced anatomically if joint-preserving treatment is selected. If anatomic reduction cannot be obtained, other treatment options such as arthroplasty should be considered.


Ethical issues associated with genetic counseling in the context of adolescent psychiatry.
Genetic counseling is a well-established healthcare discipline that provides individuals and families with health information about disorders that have a genetic component in a supportive counseling encounter. It has recently been applied in the context of psychiatric disorders (like schizophrenia, bipolar disorder, schizoaffective disorder, obsessive compulsive disorder, depression and anxiety) that typically appear sometime during later childhood through to early adulthood. Psychiatric genetic counseling is emerging as an important service that fills a growing need to reframe understandings of the causes of mental health disorders. In this review, we will define psychiatric genetic counseling, and address important ethical concerns (we will particularly give attention to the principles of autonomy, beneficence, non-maleficence and justice) that must be considered in the context of its application in adolescent psychiatry, whilst integrating evidence regarding patient outcomes from the literature. We discuss the developing capacity and autonomy of adolescents as an essential and dynamic component of genetic counseling provision in this population and discuss how traditional viewpoints regarding beneficence and non-maleficence should be considered in the unique situation of adolescents with, or at risk for, psychiatric conditions. We argue that thoughtful and tailored counseling in this setting can be done in a manner that addresses the important health needs of this population while respecting the core principles of biomedical ethics, including the ethic of care.


Classroom quality as a predictor of first graders' time in non-instructional activities and literacy achievement.
This study investigated how quality of the classroom learning environment influenced first grade students' (n=533) time spent in two non-instructional classroom activities (off-task and in transition) and their subsequent literacy outcomes. Hierarchical linear modeling revealed that higher classroom quality was related to higher student performance in reading comprehension and expressive vocabulary. Further, classroom quality predicted the amount of time students spent off-task and in transitions in the classroom, with slopes of change across the year particularly impacted. Mediation effects were detected in the case of expressive vocabulary such that the influence of classroom quality on students' achievement operated through students' time spent in these non-instructional activities. Results highlight the importance of overall classroom quality to how students navigate the classroom environment during learning opportunities, with subsequent literacy achievement impacted. Implications for policy and educational practices are discussed.


A Micro-evolutionary Change in Target Binding Sites as a Key Determinant of Ultrabithorax Function in Drosophila.
Hox genes encode Homeodomain-containing transcription factors, which specify segmental identities along the anterior-posterior axis. Functional changes in Hox genes have been directly implicated in the evolution of body plans across the metazoan lineage. The Hox protein Ultrabithorax (Ubx) is expressed and required in developing third thoracic (T3) segments in holometabolous insects studied so far, particularly, of the order Coleoptera, Lepidoptera and Diptera. Ubx function is key to specify differential development of the second (T2) and T3 thoracic segments in these insects. While Ubx is expressed in the third thoracic segment in developing larvae of Hymenopteran Apis mellifera, the morphological differences between T2 and T3 are subtle. To identify evolutionary changes that are behind the differential function of Ubx in Drosophila and Apis, which are diverged for more than 350 million years, we performed comparative analyses of genome wide Ubx-binding sites between these two insects. Our studies reveal that a motif with a TAAAT core is a preferred binding site for Ubx in Drosophila, but not in Apis. Biochemical and transgenic assays suggest that in Drosophila, the TAAAT core sequence in the Ubx binding sites is required for Ubx-mediated regulation of two of its target genes studied here; CG13222, a gene that is normally upregulated by Ubx and vestigial (vg), whose expression is repressed by Ubx in T3. Interestingly, changing the TAAT site to a TAAAT site was sufficient to bring an otherwise unresponsive enhancer of the vg gene from Apis under the control of Ubx in a Drosophila transgenic assay. Taken together, our results suggest an evolutionary mechanism by which critical wing patterning genes might have come under the regulation of Ubx in the Dipteran lineage.


Fibroblast growth factor 23 leads to endolysosomal routing of the renal phosphate cotransporters NaPi-IIa and NaPi-IIc in vivo.
Na+-dependent phosphate cotransporters NaPi-IIa and NaPi-IIc, located at the brush-border membrane of renal proximal tubules, are regulated by numerous factors, including fibroblast growth factor 23 (FGF23). FGF23 downregulates NaPi-IIa and NaPi-IIc abundance after activating a signaling pathway involving phosphorylation of ERK1/2 (phospho-ERK1/2). FGF23 also downregulates expression of renal 1-α-hydroxylase (Cyp27b1) and upregulates 24-hydroxylase (Cyp24a1), thus reducing plasma calcitriol levels. Here, we examined the time course of FGF23-induced internalization of NaPi-IIa and NaPi-IIc and their intracellular pathway toward degradation in vivo. Mice were injected intraperitoneally with recombinant human (rh)FGF23 in the absence (biochemical analysis) or presence (immunohistochemistry) of leupeptin, an inhibitor of lysosomal proteases. Phosphorylation of ERK1/2 was enhanced 60 min after rhFGF23 administration, and increased phosphorylation was still detected 480 min after injection. Colocalization of phospho-ERK1/2 with NaPi-IIa was seen at 60 and 120 min and partly at 480 min. The abundance of both cotransporters was reduced 240 min after rhFGF23 administration, with a further reduction at 480 min. NaPi-IIa and NaPi-IIc were found to colocalize with clathrin and early endosomal antigen 1 as early as 120 min after rhFGF23 injection. Both cotransporters partially colocalized with cathepsin B and lysosomal-associated membrane protein-1, markers of lysosomes, 120 min after rhFGF23 injection. Thus, NaPi-IIa and NaPi-IIc are internalized within 2 h upon rhFGF23 injection. Both cotransporters share the pathway of clathrin-mediated endocytosis that leads first to early endosomes, finally resulting in trafficking toward the lysosome as early as 120 min after rhFGF23 administration.NEW & NOTEWORTHY The hormone fibroblast growth factor 23 (FGF23) controls phosphate homeostasis by regulating renal phosphate excretion. FGF23 acts on several phosphate transporters in the kidney. Here, we define the time course of this action and demonstrate how phosphate transporters NaPi-IIa and NaPi-IIc are internalized.


Associations of single and multiple organophosphate pesticide exposure with female infertility in the USA: data from the 2015-2018 National Health and Nutrition Examination Survey.
Substantial evidence has shown that organophosphate pesticide (OPP) exposure altered the reproductive system functions, such as prolonged menstrual cycles, sexual hormone imbalance, and changes in ovarian weight. However, the association of OPP exposure with female infertility is unclear. We explored the relationships of four single OPP metabolites and their mixed exposure with self-reported infertility among women aged 20-50 in the USA using the data from two cycles (2015-2016 and 2017-2018) of the National Health and Nutrition Examination Survey (NHANES) by multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC). Eventually, 659 females were included in our study. Among these females, 77 participants were ever infertile. Multiple logistic regression showed that the odds ratios (ORs) in the second and third tertiles of dimethylphosphate (DMP) for female infertility were 2.53 (95% confidence interval (95%CI): 1.20-5.32, P value = 0.016) and 2.96 (95%CI: 1.18-7.47, P value = 0.023) compared to the lowest tertile after adjusting for all covariates (P for trend = 0.022). A significantly positive association between the mixed OPP metabolites and infertility was observed in the BKMR model, in which DMP had the highest posterior inclusion probability (PIP = 0.741). The QGC model showed similar results, in which OPP metabolite mixtures increased the risk of female infertility, with DMP as a significantly positive contributor to the outcome. This study revealed the potential harm of OPP mixtures for female infertility in the USA, and DMP played the most critical role in female infertility risk among all OPP metabolites.


The radiation dose to surgical personnel during intraoperative radioimmunoscintimetry.
To estimate the radiation exposure to surgical personnel caused by intraoperative radioimmunoscintimetry, we measured dose rates at different distances from patients who had been injected with 950 MBq technetium-99m-labelled intact carcinoembryonic antigen (CEA)-specific antibodies (Szintimun CEA, Behring AG Marburg, FRG) for immunoscintigraphy 24 h earlier. At 0.05 m (corresponding to working positions during surgery) we found 2.0-16.0 microSv h-1 (average 6.4), which is similar to results for nuclear medicine staff. Thus, if radioimmunoscintimetry is to become a routine procedure, according to national regulations in some countries of the European Communities surgical personnel might be regarded as professionally exposed to radiation.


Toxicity mechanism of acrolein on DNA damage and apoptosis in BEAS-2B cells: Insights from cell biology and molecular docking analyses.
Acrolein is a hazardous air pollutant for humans and is responsible for many pulmonary diseases, but the underlying mechanisms have not been completely elucidated. This work is focused on the genotoxicity effects of human bronchial epithelial (BEAS-2B) cells induced by acrolein (20, 40, 80 μM). The molecular mechanism was investigated base on DNA damage and mitochondrial apoptosis pathways. The results showed that after exposure to acrolein, the cell viability, glutathione (GSH) of BEAS-2B cells were reduced. Reactive oxygen species (ROS) level significantly increased, accompanied by increased levels of DNA damage-related indicators 8-hydroxy-2 deoxyguanosine (8-OHdG), DNA content of comet tail (Tail DNA%), olive tail moment (OTM), and nucleus morphology. Cell arrested at the G2/M phase. Then, the DNA damage response (DDR) signaling pathway (Ataxia-telangiectasia-mutated (ATM) and Rad-3-related (ATR)/Chk1 and ATM/Chk2) and the consequent cell cycle checkpoints were activated. The expression of γ-H2AX was significantly increased, indicating that acrolein induced DNA double-strand breaks. Molecular docking assay showed that acrolein bound to DNA in a spontaneous process. Moreover, mitochondrial apoptosis pathway involved in apoptosis, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) content of BEAS-2B cells were significantly reduced, and the apoptosis rate was significantly increased. The protein expression of Bax/Bcl-2 and Cleaved Caspase-3 were increased, and JNK signaling pathway was activated. All the results indicated that acrolein induced DNA damage, activated DDR and mitochondrial apoptosis pathways, which might be the pivotal factors to mediate cytotoxicity in BEAS-2B cells.


Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway.
During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities.


Efficacy of cortisone injection in treatment of trigger fingers and thumbs.
One hundred eight trigger fingers and thumbs in 74 consecutive patients were treated by injections of triamcinalone and followed for an average of 3 1/2 years. Minimum follow-up was 1 year. Eighty four percent of trigger fingers and 92% of trigger thumbs were cured with a single injection, and a repeat injection for treatment of recurrent symptoms raised these figures to 91% and 97%, respectively. All injections were done by one physician. There were no complications. We conclude that intrasynovial injection of a steroid compound is the appropriate initial treatment for trigger fingers and thumbs.


Triple assessment breast clinics: The value of clinical core biopsies.
Triple Assessment Breast Clinics are designed for rapid diagnosis of symptomatic patients. When there is no concordance between clinical and radiological assessment, clinicians perform clinical core biopsies. In patients with a clinically suspicious examination (S4, S5) and normal imaging, clinically guided core biopsy should be performed as per NCCP guidelines. However, substantial research does not exist on the diagnostic value or use of clinical core biopsies in non-suspicious palpable (S3) lesions and practices differ in each health system. The aim of this research was to assess the diagnostic value of clinical core biopsies in nonsuspicious, probably benign palpable breast lesions (S3) where image guided cores were not indicated (R1/R2). The cohort consisted of patients undergoing clinical core biopsies at a Symptomatic Breast Unit from January 2014 to 2019. Data regarding patient demographics, outcome of triple-assessment and incidence of malignancy were obtained from a prospectively maintained database and results were analysed using Minitab 2018. Three hundred and sixty patients had a clinical core biopsy performed in this period. Clinical examination scores for these patients were S1/S2 (66), S3 (277), S4 (15), and S5 (2). Radiology Scores were R1/R2 (355) and R3(5). Two patients with clinical score S3 (0.6%) were diagnosed with breast cancer due to their clinical cores. Both patients had normal mass imaging. There was no association between uncertain palpable breast lesions (S3), and atypia or malignancy on biopsy results when breast imaging was normal (P = 0.43, χ2 test). Despite clinical core biopsies being used in triple assessment, there is no certainty in their value except that there is high clinical suspicion. Imaging modalities are constantly improving and are already well established. When the patient is assigned a clinical score of S3 and has normal radiology, a clinical core biopsy is not required in most cases.


Relationship between seasons and pregnancy rates during intrauterine insemination. A historical cohort.
The underlying cause of seasonal infertility in humans is unclear, but is likely to be -multifactorial. The aim of our study was to compare the pregnancy rates among infertile women who underwent induced ovulation and intrauterine insemination (IUI) with the season in which the fertility treatment was performed. This retrospective cohort study was conducted on 466 patients who were treated in the reproductive endocrinology and infertility outpatient clinic of a tertiary-level women's healthcare and maternity hospital. Retrospective demographic, hormonal and ultrasonographic data were obtained from the patients' medical records. Clomiphene citrate or gonadotropin medications were used for induced ovulation. The patients were divided into four groups according to the season (spring, winter, autumn and summer) in which fertility treatment was received. Clinical pregnancy rates were calculated and compared between these four groups. There were no significant differences between the seasonal groups in terms of age, infertility type, ovarian reserve tests, duration of infertility, medications used or length of stimulation. A total of 337 patients (72.3%) were treated with clomiphene citrate and 129 (27.7%) with gonadotropin; no significant difference between these two groups was observed. The clinical pregnancy rates for the spring, winter, autumn and summer groups were 15.6% (n = 24), 8.6% (n = 9), 11.5% (n = 13) and 7.4% (n = 7), respectively (P = 0.174). Although the spring group had the highest pregnancy rate, the rates of successful IUI did not differ significantly between the seasonal groups.


Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.
The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).


Dose Optimization of Vancomycin Using a Mechanism-based Exposure-Response Model in Pediatric Infectious Disease Patients.
This study aimed to determine the appropriate vancomycin dosage, considering patient size and organ maturation, by simulating the bacterial count and biomarker level for drug administration in pediatric patients with gram-positive bacterial (GPB) infections. Natural language processing for n-gram analysis was used to detect appropriate pharmacodynamic (PD) markers in infectious disease patients. In addition, a mechanism-based model was established to describe the systemic exposure and evaluate the PD marker simultaneously in pediatric patients. A simulation study was then conducted by using a mechanism-based model to evaluate the optimal dose of vancomycin in pediatric patients. C-reactive protein (CRP) was selected as a PD marker from an analysis of ~270,000 abstracts in PubMed. In addition, clinical results, including the vancomycin plasma concentrations and CRP levels of pediatric patients (n = 93), were collected from electronic medical records. The vancomycin pharmacokinetic model with allometric scaling and a maturation function was built as a one-compartment model, with an additional compartment for bacteria. Both the effects of vancomycin plasma concentrations on the destruction of bacteria and those of bacteria on CRP production rates were represented by using a maximum achievable effect model (Emax model). Simulation for dose optimization was conducted not only by using the final model but also by exploring the possibility of therapeutic failure based on the MICs of vancomycin for GPB. Clinical cure was defined as when the CRP level fell below the upper limit of the normal range. Our dose optimization simulations suggested a vancomycin dosage of 10 mg/kg every 8 h as the optimal maintenance dose for pediatric patients with a postconceptual age <30 weeks and 10 mg/kg every 6 h for older children, aged up to 12 years. In addition, the MIC of 3 μg/mL was assessed as the upper concentration limit associated with successful vancomycin treatment of GPB infections. This study confirmed that the changes in bacterial counts and CRP levels were well described with mechanistic exposure-response modeling of vancomycin. This model can be used to determine optimal empiric doses of vancomycin and to improve therapeutic outcomes in pediatric patients with GPB.


Prevalence of the prothrombin 20210 G-to-A variant in blacks: infants, patients with venous thrombosis, patients with myocardial infarction, and control subjects.
A genetic variation in the prothrombin gene is located in the 3-untranslated region at position 20210 where a G-->A transition occurs. The prevalence of the mutation is 1% to 2% in white populations, and the mutation is associated with an increased risk of venous thrombosis and myocardial infarction. We report the prevalence of the A allele in blacks at birth; in black control subjects with no history of heart attack, stroke, or blood clots; in black patients with venous thrombosis; and in black patients with myocardial infarction. Among 318 infants, the prevalence of the A allele was 0.2% (1 heterozygote), with an exact, one-sided upper 95% confidence limit of 0.7%. Among 185 control subjects the variant was absent, yielding an exact, one-sided upper 95% confidence limit of 0.8% for the A allele. The heterozygous genotype was found in 2 of 91 subjects with deep vein thrombosis and in none of 123 subjects with myocardial infarction. The very low prevalence of the A allele indicates that the prothrombin variant is not a major cause of venous thrombosis or myocardial infarction in blacks.


Action of monovalent cations on the biological properties of PR toxin, a mycotoxin from Penicillium roqueforti.
PR toxin impairs liver cell metabolism by inhibiting RNA and protein synthesis. In vitro, the drug inhibits the transcription carried out by isolated rat liver nuclei and the translation promoted by polysomes. The action of monovalent cations on the biological activities of PR toxin has been studied. The increased ionic strength due to the presence of salt in the incubation medium, lowers the inhibitory action of PR toxin on in vitro transcription and translation activities; this action is reversible. Besides the overall effect of the ionic strength, ammonium salts possess a specific ability to suppress irreversibly the biological properties of PR toxin (in vivo toxicity and capacity of inhibiting RNA and protein synthesis). The mechanism of this action is discussed.


Effect of overground gait training with 'Mobility Assisted Robotic System-MARS' on gait parameters in patients with stroke: a pre-post study.
To observe the effect of overground gait training with 'Mobility Assisted Robotic System-MARS' on gait parameters in patients with stroke. This prospective pre-post study was conducted in a tertiary teaching research hospital with 29 adult stroke patients, with age up to 65 years. Patients fulfilling the inclusion criteria were divided in 2 groups based on the duration of stroke (≤ 6 months-sub-acute & > 6 months-chronic stroke) and provided overground gait training with MARS robot for 12 sessions (1 h/session) over a period of 2-3 weeks. Primary outcome measures were; 10-Meter walk test-10MWT, 6-min' walk test-6MWT and Timed up & Go-TUG tests. Secondary outcome measures were Functional Ambulation Category-FAC, Modified Rankin Scale-MRS and Scandinavian Stroke Scale-SSS. No adverse events were reported. Twenty-five patients who were able to perform 10-MWT at the beginning of study were included in the final analysis with 12 in sub-acute and 13 in chronic stroke group. All primary and secondary outcome measures showed significant improvement in gait parameters at the end of the training (p < 0.05) barring 10-Meter walk test in sub-acute stroke group (p = 0.255). Chronic stroke group showed significant minimum clinically important difference-MCID difference in endurance (6MWT) at the end of the training and both groups showed better 'minimal detectable change-MDC' in balance (TUG) at the end of the training. Patients in both the groups showed significant improvement in walking speed, endurance, balance and independence at the end of the training with overground gait training with MARS Robot. National Clinical Trial Registry of India (CTRI/2021/08/035695,16/08/2021).


Modulation of T-cell ontogeny by transplacental benzo(a)pyrene.
Transplacental exposure to the carcinogen, benzo(a)pyrene BaP, leads to depressed immune function and increased tumor incidence in mice. This paper reports ontogenetic T-cell changes in BALB/c mice after exposure to BaP in utero. Monoclonal antibodies (MAbs) were produced to fetal liver T-cells (FLT) and newborn spleen (NBS) lymphocytes purified from offspring of pregnant BALB/c mice that were given one injection of BaP (150 mg/kg body weight) in mid-gestation (day 11-13). The MAbs reacted with two T-cell membrane antigens (FLT and NBS) found in fetal liver, neonatal and adult thymus and spleen. Lymphocytes of BaP-exposed 19-day fetuses showed decreased subpopulation frequencies (P < 0.05) in fetal liver total T-cells (from 56% to 16%), Ly1 cells (from 33% to 9%), and Ly2 cells (from 56% to 1%) compared with untreated controls. In contrast, BaP increased the subpopulation frequencies (P < 0.05) in FLT cells in fetal liver (from 20% to 52%) and in newborn spleen (from 21% to 51%), and increased NBS cells in newborn spleen (from 24% to 59%). The increased frequency in FLT and NBS cells was due to their relative resistance to BaP toxicity and/or BaP-enhanced proliferation in the neonatal period. Compared with untreated controls, BaP treatment resulted in reduced numbers of T-cells in fetal liver and showed a selective toxicity for Ly1 cells (89% reduction) and Ly2 cells (99% reduction), whereas FLT cells were not reduced and NBS cells were reduced by 60%. Six-week-old juvenile mice exposed to BaP in utero showed recovery of total T-cells to control levels in spleen and thymus, but showed depletion (P < 0.01) in thymic FLT cells (from 81% to 12%) and in splenic NBS cells (from 55% to 16%). The monoclonal antibodies developed for this study recognize novel cellular changes in the murine immune system that are associated with transplacental BaP. The FLT and NBS antigens may be useful biomarkers for developmental immune dysfunctions in progeny exposed to BaP in utero.


Loading into and electro-stimulated release of peptides and proteins from chondroitin 4-sulphate hydrogels.
Chondroitin 4-sulphate (CS) hydrogels were examined as potential matrices for the electro-controlled delivery of peptides and proteins. A CS hydrogel, cross-linked with ethylene glycol diglycidyl ether, and with a swelling ratio of 20, was used to study the influence of molecular size and shape of guest molecules on loading and release rates. Three positively charged molecules of different molecular weights (vasopressin MW 1084, aprotinin MW 6512 and lysozyme MW 14,400), and one negatively charged protein (bovine serum albumin MW 67,000) were used as model solutes. The hydrogels were loaded by equilibrium swelling. As a result, the three positively charged peptide and proteins were found to be concentrated in the gels, most likely due to ionic attraction between the negative charges in the gel polymeric backbone and the positively charged solutes. No such concentration of solute in the gel was seen for the negatively charged albumin. The latter is presumably loaded passively by diffusing in the water phase of the gel. The loading efficiency (indicated by the loading rate and the total amount of solute loaded in the gel) was found to increase with decreasing molecular size of solute. Electro-stimulated release of the loaded peptide and proteins was followed for 3 h during which an electric field was applied in pulses of 5 V (pulse duration and pulse interval were both of 20 min). The release of lysozyme and aprotinin from CS hydrogels responded to electrical pulses. On the other hand, vasopressin and albumin were largely released by passive diffusion and their release could not be electrically controlled. This work shows that the size of the guest molecule is an important parameter when electrically-stimulated drug release is desired, but further work obviously needs to be carried out with a larger range of molecular weights and conformations.


Cleavage of the indium(III) octaethyloxophlorin dimer, {In(III)(OEPO)}2, with Lewis bases. Importance of outer-sphere hydrogen bonding in adduct structures.
Splitting of the oxygen-bridged dimer {In(III)(OEPO)}(2) [where (OEPO)(3-) is the trianion of octaethyloxophlorin] by potential axial ligands has been examined and compared to results obtained previously for the cleavage of {Fe(III)(OEPO)}(2). Treatment of {In(III)(OEPO)}(2) with an excess of imidazole (im) produced the crystalline complex {(im)(2)In(III)(OEPO...im)}(2).(im)(2)In(III)(OEPO).2Cl(2)C(6)H(4). This solid contains two different (im)(2)In(III)(OEPO) units that are bridged through hydrogen bonding by an uncoordinated imidazole. Treatment of {In(III)(OEPO)}(2) with an excess of pyridine (py) produced (py)(2)In(III)(OEPO), which is isostructural with (py)(2)Fe(III)(OEPO). Although {Fe(III)(OEPO)}(2) reacted with xylyl isocyanide (xylylNC) to form the novel free-radical complex (2,6-xylylNC)(2)Fe(II)(OEPO(*)) [where (OEPO(*))(2-) is the radical dianion of octaethyloxophlorin], {In(III)(OEPO)}(2) was unreactive toward xylyl isocyanide.


Tumefactive demyelinating CNS lesion in a 60-year-old woman with familial Mediterranean fever.
We here report on a 60-year-old woman with familial Mediterranean fever (FMF) who developed cognitive impairment 16 years after initial diagnosis. On MRI, a new extensive white matter lesion in the right frontal lobe with mild local mass effect but without contrast enhancement was detectable and classified as a tumefactive lesion. Additional MR spectroscopy showed markedly increased choline levels accompanied by a significant lactate peak, highly suggestive of a low-florid demyelinating process. Although diffuse central nervous system (CNS) lesions have been described in single FMF cases, tumefactive lesions have not been observed in FMF patients without concomitant multiple sclerosis. In summary, this case highlights rare differential diagnoses of atypical, inflammatory CNS lesions and the clinical utility of MR spectroscopy.


RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors.
Gain-of-function mutations in the LRRK2 gene cause Parkinson's disease (PD), characterized by debilitating motor and non-motor symptoms. Increased phosphorylation of a subset of RAB GTPases by LRRK2 is implicated in PD pathogenesis. We find that increased phosphorylation of RAB3A, a cardinal synaptic vesicle precursor (SVP) protein, disrupts anterograde axonal transport of SVPs in iPSC-derived human neurons (iNeurons) expressing hyperactive LRRK2-p.R1441H. Knockout of the opposing protein phosphatase 1H (PPM1H) in iNeurons phenocopies this effect. In these models, the compartmental distribution of synaptic proteins is altered; synaptophysin and synaptobrevin-2 become sequestered in the neuronal soma with decreased delivery to presynaptic sites along the axon. We find that RAB3A phosphorylation disrupts binding to the motor adapter MADD, potentially preventing formation of the RAB3A-MADD-KIF1A/1Bβ complex driving anterograde SVP transport. RAB3A hyperphosphorylation also disrupts interactions with RAB3GAP and RAB-GDI1. Our results reveal a mechanism by which pathogenic hyperactive LRRK2 may contribute to the altered synaptic homeostasis associated with characteristic non-motor and cognitive manifestations of PD.


The effects of in-vehicle tasks and time-gap selection while reclaiming control from adaptive cruise control (ACC) with bus simulator.
This research aimed to find out the effects of in-vehicle distractions and time-gap settings with a fix-based bus driving simulator in a following scenario. Professional bus drivers were recruited to perform in-vehicle tasks while driving with adaptive cruise control (ACC) of changeable time-gap settings in freeway traffic. Thirty subjects were divided equally into three groups for different in-vehicle task modes (between subjects), including no task distraction, hands-free, and manual modes. Further, time-gap settings for the experimental ACC were: shorter than 1.0 s, 1.0-1.5 s, 1.5-2.0 s, and longer than 2.0 s (within subjects). Longitudinal (mean headway, forward collision rate, and response time) and lateral control (mean lateral lane position and its standard deviation) performance was assessed. In the results, longitudinal control performance was worsened by both shorter time-gaps and heavier in-vehicle tasks. But the interaction indicated that the harm by heavier in-vehicle distraction could be improved by longer time-gaps. As for the lateral control, it would only be negatively affected by shorter time-gap settings. This research indicates the effects of time-gaps and in-vehicle distraction, as well as the interaction. Proper time-gap selection under different in-vehicle distractions can help avoid accidents and keep safe.


Preventable mortality among sexual minority Canadians.
Epidemiologic studies point to multiple health inequities among sexual minority people, but few studies have examined mortality. Some causes of death are more preventable than others, and access to prevention is theorized to follow patterns of access to social and material resources. The objective of this study is to compare estimates of preventable mortality between sexual minority (SM)-i.e., bisexual, lesbian, gay-and heterosexual adults in Canada. A population-based retrospective cohort with 442,260 (unweighted N) Canadian adults, ages 18-59 years, was drawn from the Canadian Community Health Survey/Canadian Mortality Database linked database (2003-2017). The Rutstein preventability rating index was used to classify cause-specific mortality (low/high). Longitudinal analyses were conducted using Cox proportional hazards models. SM respondents had higher hazard of all-cause mortality (unadjusted hazard ratio [uHR] 1.28, 95% CI 1.06, 1.55). The uHR increased when the outcome was limited to highly-preventable causes of mortality (uHR 1.43, 95% CI 1.14, 1.80). The uHR further increased in sensitivity analyses using higher thresholds of the Rutstein index. SM respondents had higher hazard of cause-specific mortality for heart disease (uHR 1.53, 95% CI 1.03, 2.29), accidents (uHR 1.97, 95% CI 1.01, 3.86), HIV (uHR 75.69, 95% CI 18.77, 305.20), and suicide (uHR 2.22, 95% CI 0.93, 5.30) but not for cancer (uHR 0.86, 95% CI 0.60, 1.25). The adjusted HR (aHR) for highly-preventable mortality was not attenuated by adjustment for confounders (aHR 1.57, 95% CI 1.20, 2.05) but was reduced by adjustment for hypothesized mediators relating to access to social and material resources (marital status, children, income, education; aHR 1.11, 95% CI 0.78, 1.58). Preventable mortality was elevated for SM Canadians compared to heterosexuals. Early and broad access to sexual minority-affirming primary and preventive healthcare should be expanded.


Sensory Evolution: Trouble in the Cherry Orchard.
Understanding how and why some species become pests, while their relatives remain harmless, might help us control them. A new study looks at how sensory mechanisms evolved in an emerging pest fly species.


Management science.
Many dentists believe that they are poor businessmen. Some even take the view that business is none of their business. Neither attitude is realistic. This is the first of a series of six articles which, by outlining some basic ideas, will demonstrate that efficient practice management is not only desirable, but also achievable.


Approximation of optimal surface parameterizations and the application in cerebral cortex mapping.
Optimal parameterizations of surface meshes are useful in the mapping and visualization of the cerebral cortex, the outer layer of the human brain. We propose two new methods to compute approximations of the optimal parameterizations, and apply these methods to human cortical surface meshes extracted from magnetic resonance images. Our methods approximate the parameterizations in a low-dimensional subspace spanned by the coordinate vectors of an initial parameterization and the low-frequency eigenvectors of a mesh Laplacian. This low-dimensional approximation reduces the computational complexity while minimizing the error.


Role of thenar electromyography in the evaluation of carpal tunnel syndrome.
In the evaluation of CTS, electromyography of various myotomes as well as proximal and distal muscles remains quite useful in helping to assess other clinically suspected differentials such as plexopathy, systemic neuropathies, radiculopathies, and proximal nerve entrapments. With regards to T-EMG specifically, it can provide information regarding axonal loss; however, it only crudely estimates relative severity and prognosis. These are better and less painfully determined by nerve conduction studies. The addition of nerve conduction studies to the clinical assessment gives one the ability to diagnose, determine severity and prognosis, and determine best management. The addition of T-EMG in typical cases of CTS causes excess pain and adds little to the information already gained. Therefore the author suggests that T-EMG be reserved for atypical or unusual presentations when additional information is needed such as when nerve conduction studies cannot be performed or when the pathology is potentially aggressive causing significant axonal injury over a short time.


Effect of zinc on the immune status of zinc-depleted AIDS related complex patients.
Zinc deficiency has been recently reported in AIDS patients to be associated with a decrease in T helper cells. The effect of zinc supplementation was evaluated in 5 ARC patients and 5 control subjects using lymphocyte subset counts, blast transformation and chemiluminescence of polymorphonuclear leukocytes. Zinc was analysed by atomic absorption spectrophotometry. T-cell subsets were quantified by cytofluorometry. Chemiluminescence of PMN was measured by phagocytosis of opsonized zymosan. The ARC patients had significantly lower zinc concentrations in the RBC prior to supplementation (p < 0.05). This level increased following the administration of zinc gluconate. This increase was accompanied by (i) an increase in HLA.Dr + cells with no CD4 CD8 ratio alteration; (ii) a stimulation of lymphocyte transformation and PMN chemiluminescence particularly after 15 days' high zinc supplementation. Such a reconstitution in specific and non specific immune functions in ARC patients may warrant further investigation.


Quantification of PET Myocardial Blood Flow.
The aim of this review is to provide an update on quantification of myocardial blood flow (MBF) with positron emission tomography (PET) imaging. Technical and clinical aspects of flow quantification with PET are reviewed. The diagnostic and prognostic values of myocardial flow quantification have been established in numerous studies and in various populations. MBF quantification has also shown itself to be particularly useful in the assessment of coronary microvascular dysfunction and in evaluation of cardiac allograft vasculopathy. Overall, myocardial flow reserve (MFR) and hyperemic MBF can lead to improved risk stratification by providing information complementary to that of other markers of disease severity, such as fractional flow reserve. Flow quantification enhances MPI's ability to detect both significant epicardial disease and microvascular dysfunction. With recent technological and methodological advances, flow quantification with PET is no longer restricted to cyclotron-equipped academic centers.


Early-life events. Effects on aging.
During the last two decades, a considerable body of evidence has emerged showing that circumstances during the fetal period and childhood may have lifelong programming effects on different body functions with a considerable impact on disease susceptibility. From a medical point of view, these long-term effects are today referred to as the Developmental Origins of Health and Disease (DOHaD) concept. The DOHaD concept may have a fundamental impact on our ideas about when and how to intervene in order to prevent aging-related loss of function and disease. The aim of this review is to provide a synopsis of epidemiological findings relating early-life conditions with key aging-related disorders, including cardiovascular disease, type 2 diabetes, depression, cognitive impairments and osteoporosis. There are several mechanisms that have been suggested as linking early-life events with late-life disease. This review will discuss programming of the hypothalamic-pituitary-adrenal axis function as one of the best characterised examples of such mechanisms.


Myeloma cells: surface morphology as seen by scanning and transmission electron microscopy.
Cells from cultured murine myeloma cell lines and circulating leukemic plasma cells from two patients with generalized myeloma were studied by transmission and scanning electron microscopy. Both circulating and cultured cells exhibited consistent surface architectures. Microvilli and varying numbers of prominent blebs of different sizes were seen. The presence of surface blebs is a characteristic feature of secreting and nonsecreting myeloma cells.


Mechanisms for the Sex-Specific Effect of H. Pylori on Risk of Gastroesophageal Reflux Disease and Barrett's Esophagus.
Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.


Electron microscopy of sporulation in Schwanniomyces alluvius.
Sporulation in Schwanniomyces alluvius appeared to be preceded by fusion of a mother and daughter cell. Meiosis probably occurred in the mother cell and one or two spores were formed in the latter. A study of thin sections showed that the spore wall developed from a prospore wall. The mature spore wall consisted of a broad light inner layer and a thinner dark outer layer including warts. An equatorial ledge was present. During germination in the ascus, a new light inner layer was formed and the old layers of the spore wall partly broke up. Ascospores in a strain of S. persoonii had a different wall structure in that the dark layer had changed into light areas separated by dark material which formed bulges at the surface.


Pseudoparadoxical impulsivity in restrictive anorexia nervosa: a consequence of the logic of scarcity.
To explain an apparently paradoxical pattern wherein sufferers of restrictive anorexia nervosa exhibit both rigorous self-restraint and episodic impulsivity. The experimental, historical, and clinical literatures were examined for evidence of psychological and behavioral changes accompanying severe dietary constriction; such changes were noted and compared with those reported to occur in anorexics. Increased impulsivity in association with dietary constriction is described in diverse literatures. A number of lines of evidence suggest that the serotonergic system mediates this change. Many forms of impulsivity can be understood as having once constituted fitness-enhancing responses to resource scarcity. It is suggested that an evolved psychological mechanism calibrates the individual's sensitivity to risk in light of future prospects. Self-injurious behaviors are explicable as misfirings of such a mechanism. Similarly, excessive exercising by anorexics may reflect the misdirection of reward systems that normally encourage adaptive increases in ranging behavior under conditions of scarcity.


Unexpected extra-renal effects of loop diuretics in the preterm neonate.
The loop diuretics furosemide and bumetanide are commonly used in neonatal intensive care units (NICUs). Furosemide, because of its actions on the ubiquitous Na(+) -K(+) -2Cl(-) isoform cotransporter and its promotion of prostanoid production and release, also has non-diuretic effects on vascular smooth muscle, airways, the ductus arteriosus and theoretically the gastrointestinal tract. Loop diuretics also affect the central nervous system through modulation of the GABA-A chloride channel. The loop diuretics have a variety of biological effects that are potentially harmful as well as beneficial. Care should be taken with the use of these agents because the range of their effects may be broader than the single action sought by the prescribing physician.


Childhood asthma and indoor allergen exposure and sensitization in Buffalo, New York.
This nested case-control study examined the association between prevalent asthma and indoor allergen sensitization and/or exposure among children (aged 5-17 years) in Buffalo, New York. The study included a self-administered questionnaire, clinical interviews, skin allergen sensitivity tests and home dust sampling for house dust mites, cat, dog, cockroach and mouse allergens. After adjusting for multiple confounders, asthma cases had higher odds of being sensitized to Der p dust mites (odds ratio [OR]=1.94, 95% confidence interval (CI): 1.13-3.35), cat (OR=1.96, 95% CI: 1.13-3.39), or dog allergens (OR=1.89, 95% CI: 1.10-3.22) than the controls. A significantly positive association between asthma status presence of cat allergen in the child's mattress (ORs: 2.61, 95% CI: 1.09-6.28) was also found. Children with both sensitization and environmental exposure to cat allergens had higher odds of asthma (OR=7.08, 95% CI: 2.12-23.62) than those who were only sensitized to cat allergen (OR=2.31, 95% CI: 1.01-5.32) or had only home exposures (OR=1.47, 95% CI: 0.47-4.65). The association between allergen sensitization and asthma was more consistent than for home exposures. The findings help to confirm the role of allergen sensitization and home exposure in regard to asthma, and suggest that both, individually and jointly, are associated with asthma.


Clay-associated microbial communities and their relevance for a nuclear waste repository in the Opalinus Clay rock formation.
Microorganisms are known to be natural agents of biocorrosion and mineral transformation, thereby potentially affecting the safety of deep geological repositories used for high-level nuclear waste storage. To better understand how resident microbial communities of the deep terrestrial biosphere may act on mineralogical and geochemical characteristics of insulating clays, we analyzed their structure and potential metabolic functions, as well as site-specific mineralogy and element composition from the dedicated Mont Terri underground research laboratory, Switzerland. We found that the Opalinus Clay formation is mainly colonized by Alphaproteobacteria, Firmicutes, and Bacteroidota, which are known for corrosive biofilm formation. Potential iron-reducing bacteria were predominant in comparison to methanogenic archaea and sulfate-reducing bacteria. Despite microbial communities in Opalinus Clay being in majority homogenous, site-specific mineralogy and geochemistry conditions have selected for subcommunities that display metabolic potential for mineral dissolution and transformation. Our findings indicate that the presence of a potentially low-active mineral-associated microbial community must be further studied to prevent effects on the repository's integrity over the long term.


Effects of preoperative hepatitis B virus infection, hepatitis C virus infection, and coinfection on the development of new-onset diabetes after kidney transplantation.
The effects of preoperative hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV plus HCV coinfection on the development of new-onset diabetes after transplantation (NODAT) remain unexplored in kidney transplant recipients (KTRs). This study examined the association between preoperative viral status (i.e., HBV, HCV, and HBC + HCV infection) and incident NODAT in a large population of Chinese KTRs. This population-based retrospective cohort study enrolled 557 subjects who underwent kidney transplantation between 1993 and 2014 at Zhongshan Hospital. Pre-, peri-, and postoperative data were extracted and analyzed. Viral status was defined by serological results for hepatitis B surface antigen and anti-HCV antibody. The cumulative incidence of NODAT was compared across four groups of KTRs with different viral status. Multivariate Cox regression models were used to estimate the effects of HBV, HCV, and HBC + HCV infection on incident NODAT after adjusting for important confounders. Patients seropositive for HCV (both HCV monoinfection and HBC + HCV coinfection) had a significantly higher cumulative incidence of NODAT than KTRs who were not infected with HCV (P < 0.05 for both). However, only HCV infection alone was found to be a risk factor for NODAT, increasing the NODAT risk 3.03-fold (95% confidence interval 1.77-5.18; P < 0.001). There was no independent correlation between HBV infection (alone or combined with HCV) and incident NODAT in KTRs. Preoperative HCV infection significantly increased the risk of NODAT in Chinese KTRs, whereas HBV infection and HBC + HCV coinfection were not correlated with NODAT development.