Structure-based discovery of a boronic acid bioisostere of combretastatin A-4.
Targeting the microtubule system represents an attractive strategy for the development of anticancer agents. In this study, we report a class of combretastatin A-4 (CA-4) analogs derivatized with a boronic acid moiety replacing the hydroxyl group on the C-ring of CA-4. Docking studies of the X-ray structures of our aryl-boronic analogs onto an X-ray structure of the alpha,beta-tubulin heterodimer suggested that cis-6 was a potent inhibitor of the colchicine binding. The model indicated that there would be strong hydrogen bonding between the boronic acid moiety and Thr-179 and Val-181 of alpha-tubulin. We demonstrate that the cis-6 boronic acid bioisostere of CA-4: (1) inhibits tubulin assembly, (2) competitively displaces colchicine, and (3) is a low-nanomolar inhibitor of human cancer cell lines. We present this isostere as a class of potent analogs of CA-4.


Synthesis, SAR and pharmacology of CP-293,019: a potent, selective dopamine D4 receptor antagonist.
A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing.


Fixed subaortic stenosis with congenital aneurysm of sinus of Valsalva--cross-sectional and Doppler echocardiographic diagnosis of a rare association.
A 13-year-old girl was diagnosed by cross-sectional and Doppler echocardiography to have the rare combination of congenital aneurysm of the right sinus of Valsalva rupturing into the right ventricular outflow tract and a discrete subaortic fibrous shelf with severe subvalvar stenosis, moderate aortic regurgitation and left ventricular dysfunction. The findings were confirmed at cardiac catheterisation and surgery.


Good parenting: Making a difference.
The relevance of the quality of parenting to outcomes for children is reviewed, as well as research findings on the important dimensions of parenting in the early years. Some of the limitations of current parenting research are outlined. The contributory parent and child factors that mediate outcomes are identified, and the ways in which they interact in a bi-directional and dynamic process to determine the quality of parenting and the parent-child relationship. This information is applied to the task of parenting neonates and infants, and interventions are identified that indicate the scope and type of improvements or enhancements to parenting capacity that can be achieved. Particular issues and problems relating to the parenting of neonates or infants with special needs are briefly discussed, as well as promising initiatives to enable the care of ill babies to be more relationship-based and family centred.


Silver ion-induced tension development and membrane depolarization in frog skeletal muscle fibres.
Silver ions elicit dose-dependently a transient contracture in single fibres of bull-frog toe muscle placed in 0-Ca2+, Cl- -free MOPS solution containing 3 mM Mg2+ and NO3-. To elucidate the mechanisms involved, changes in membrane potential and in tension development were continuously measured following exposure to Ag+. The effect of Ag+ on contraction in fibres in which the membrane had been depolarized by elevating the external K+ concentration was also examined. The major findings of this investigation are as follows. (1) The mechanical threshold was shifted towards more negative potentials by 5 mV (-51 to -56 mV), when Ca2+ and Cl- in the Ringer's solution were replaced with Mg2+ and NO3-, respectively. (2) On the exposure of the fibres to 5 microM Ag+, the membrane potential decreased by 1.6 mV from -87.8 mV and tension was developed. (3) In fibres soaked in a solution containing 10 mM K+ (corresponding to a membrane potential of -69.5 mV), 5 microM Ag+ produced a large contracture similar to that seen in the control solution. (4) The Ag+-induced contracture was inactivated when more than 20 mM K+ was used. (5) The membrane depolarization evoked by either 20 or 50 microM Hg2+ did not produce contraction. (6) Muscle fibres which had been exposed to 20 microM Hg2+ for 5 min responded to 5 microM Ag+ by a transient tension development. These findings strongly suggest that Ag+-induced tension development is not associated with depolarization of the surface membrane but rather is caused by specific actions of Ag+ on membrane proteins in the T-tubules.


Chronic repetitive cooling and caffeine-induced intracellular Ca2+ elevation differentially impact adaptations in slow- and fast-twitch rat skeletal muscles.
Intracellular Ca2+ concentration ([Ca2+]i) is considered important in the regulation of skeletal muscle mass. This study tested the hypothesis that chronic repeated cooling and/or caffeine ingestion would acutely increase [Ca2+]i and hypertrophy muscles potentially in a fiber-type-dependent manner. Control rats and those fed caffeine were subjected to repeated bidiurnal treatments of percutaneous icing, under anesthesia, to reduce the muscle temperature below ∼5°C. The predominantly fast-twitch tibialis anterior (TA) and slow-twitch soleus (SOL) muscles were evaluated after 28 days of intervention. The [Ca2+]i elevating response to icing was enhanced by caffeine loading only in the SOL muscle, with the response present across a significantly higher temperature range than in the TA muscle under caffeine-loading conditions. In both the TA and SOL muscles, myofiber cross-sectional area (CSA) was decreased by chronic caffeine treatment (mean reductions of 10.5% and 20.4%, respectively). However, in the TA, but not the SOL, CSA was restored by icing (+15.4 ± 4.3% vs. noniced, P < 0.01). In the SOL, but not TA, icing + caffeine increased myofiber number (20.5 ± 6.7%, P < 0.05) and satellite cell density (2.5 ± 0.3-fold) in cross sections. These contrasting muscle responses to cooling and caffeine may reflect fiber-type-specific [Ca2+]i responses and/or differential responses to elevated [Ca2+]i.


Striatonigral degeneration with neurofibrillary tangles.
An autopsy was performed on a 48-year-old woman with clinical features of parkinsonism-plus syndrome with dominating akinesia. Neuropathological examination revealed striato-nigral degeneration (SND) and neurofibrillary tangles (NFT) characterizing progressive supranuclear palsy. Such an unusual combination of pathological findings may constitute a distinct clinico-pathological entity, with akinesia as the main clinical symptom, and with a pathological substrate of SND and NFT. We suggest that such cases may establish a separate variant within multisystem atrophies syndromes.


Perineural invasion by carcinoma of the lower lip.
Extension of lip cancer to the mental nerve and perineural spread was found in four patients. The main complaint in all cases was sensory disturbance which preceded the diagnosis of recurrence by perineural spread as well as widening of the mandibular canal. In one patient, two cranial nerves, the trigeminal and the facial were involved and one patient had bilateral neural involvement. Three patients died within 1 year of the diagnosis of perineural spread. Prevention includes the separate examination of specimens at the resection line near the mental nerve, and follow-up by examination of the lower vestible, X-ray of the mandible and monitoring of sensory disturbance.


Low glucose-sensing cells in the carotid body.
Decreased plasma glucose concentration elicits a complex neuroendocrine response that prevents or rapidly corrects hypoglycemia as required to preserve brain function; however, where and how low glucose is sensed is unknown. Here we show that low glucose increases secretion from glomus cells in the carotid bodies, sensory organs whose stimulation by hypoxia produces sympathetic activation, by a process that depends on extracellular Ca2+ influx and is paralleled by inhibition of voltage-gated K+ channels. We propose a new glucose-sensing role for the carotid body glomus cell that serves to integrate information about blood glucose and O2 levels and to activate counterregulatory responses.


Analysis of lateral flow biodetectors: competitive format.
Lateral flow (LF) biodetectors facilitate low-cost, rapid identification of various analytes. The LF cell consists of a porous membrane containing immobilized ligands at various locations. Through the action of capillary forces, a mixture of sample and reporter particles is transported to the ligand sites, where the target analytes and the reporters bind to the immobilized ligand. The concentration of the reporters is measured with a scanner. A mathematical model for two different competitive assays is constructed and used to study the performance of LF devices under various operating conditions. The model predicts the signal magnitude as a function of target analyte, reporter, and ligand concentrations, reaction rate constants, and flow rate. The predictions are compared and qualitatively agree with experimental data. The model provides insights into various experimental observations. Furthermore, the model can be used to optimize the performance of LF devices and to inexpensively and rapidly test the system under various operating conditions.


Complete genome sequence of Hymenobacter sp. DG25B, a novel bacterium with gamma-radiation resistance isolated from soil in South Korea.
A Gram-negative, rod-shaped, non-motile, gamma and UV radiation resistant bacterium Hymenobacter radioresistens DG25B was isolated from a soil sample collected in South Korea. The complete genome sequence of H. radioresistens DG25B consists of one circular chromosome (3,874,646 bp). The bacterium was isolated from gamma ray irradiated soil and contains the genomic features of enzymes involved in the nucleotide excision repair (NER) pathway that protect the damaged DNA. The genome also contains other genes involved in the efficient removal of double-strand breaks (DSB) caused by the ionizing radiations.


Factors affecting the utilization of mental health services among undergraduate students in a Nigerian University.
Under-utilization of mental health services among university students is a major public health concern. This study assessed the factors affecting the utilization of mental health services among undergraduate students. This research was a cross-sectional survey carried out among students of Afe Babalola University, Ado-Ekiti, Nigeria. A semi-structured self-administered questionnaire was used for data collection and multi-stage sampling technique was used in sampling the participants. Utilization, attitude, and health seeking behavior were categorized into good (≥50% score), and poor (<50% score), while social support was categorized into poor (8-18), moderate (19-25), and strong (26-32). Chi-square test and Logistic regression were used to assess the relationship between the categorical variables. 450 students enrolled in this study of which 52.4% were females and mean age of 19.40 ± 1.65 years. Most students showed a good attitude (87.5%), health seeking behavior (67.8%), and poor social support (69.4%) towards mental health services. There was an association between source of information (p = 0.005), health seeking behavior (p = 0.001) and utilization of mental health services. There was also a higher likelihood for students of female gender (OR: 1.621 (1.072-2.452)) and being aged above 20 years (OR: 1.331 (0.822-2.153)) to have good utilization of mental health services. Majority of the students showed good attitude and health seeking behavior towards mental health services but there was poor utilization as well as poor to moderate social support towards mental health services. Gender, age, attitude, source of information as well as health seeking behavior are important factors that can affect the utilization of mental health services among undergraduate students. Interventions targeted towards these factors should be done to ultimately improve utilization of mental health services among undergraduate students.


Neodymium-YAG laser posterior capsulotomy for the treatment of aphakic and pseudophakic pupillary block.
We examined five patients who developed pupillary block after extracapsular cataract extraction. One of the patients also had a posterior chamber intraocular lens implanted at the time of cataract operation. In all five patients, pupillary block was promptly relieved by Nd:YAG laser posterior capsulotomy.


Corrections.
[This corrects the article on p. 567 in vol. 20.][This corrects the article on p. 569 in vol. 20.].


Case reports of pediatric electrical finger burn injuries' management and late- onset complications
Pediatric electrical injuries are rare; they only constitute 2-10% of all burn causes. Determination of their actual severity may be challenging due to their small entry and exit wounds. Deep necrosis develops during electrical burns in most cases. These injuries can damage the skin, soft and bone tissues, and in children, the growth plate, which may cause secondary deformities. The objective of these case reports was the presentation of paediatric electrical finger injuries' management and late-onset complications. A 15-year-old boy touched an electric wire while changing a lightbulb, which caused a burn injury on his right index finger. During the physical examination, a 25 x 14 mm, third-degree burn was identified volarly, above the distal interphalangeal joint as an entry wound, and an 8 x 7 mm exit site occurred dorsally at the nailbed's lateral edge. Necrectomy and cross finger flap surgery were performed. The cross flap was separated three weeks after the primary reconstruction. Throughout the follow-up examinations, the ulnar deviation of the distal digit was observed. X-ray confirmed the bone atrophy of the distal phalanx base. A 2-year old girl inserted a nail into the power outlet, causing third-degree burns on her thumb around the interphalangeal joint and hypothenar region. After necrectomy, the thumb's skin defect was reconstructed with a rotated flap, while the donor site received full-thickness skin graft transplantation. The follow-up of the child is still ongoing. Long term follow-up of these patients is necessary to identify and treat late-onset complications.


Inhibition of platelet aggregation by primary amines. Evidence for a possible role of membrane-associated calcium.
The aggregation of human blood platelets by thrombin, adenosine diphosphate, wheat germ agglutinin or ristocetin was inhibited by primary amines. In general, thrombin-induced platelet aggregation was strongly affected by the amines while the effect was weak on cell aggregation by ristocetin. Usually, the diamines were stronger inhibitors of aggregation than the monoamines with cadaverine as the strongest and ethylamine as the weakest inhibitor. At concentration where platelet aggregation was inhibited, the amines neither displaced serotonin from serotonin-loaded platelets nor caused lysis of human red cells. The lectin activity of wheat germ agglutinin on human red cells was not affected by the amines indicating that the amines probably acted on platelets and not on the agglutinin. The clotting activity of thrombin on fibrinogen was partially inhibited by the amines while its esterolytic activity remained unaltered. The inhibitory action of the amines on platelet aggregation could be overcome with small amounts of calcium while other divalent cations tested had little effect. It is suggested that the amines affect platelet aggregation by interfering with the actions of membrane-associated calcium.


Using Action Research to Mentor Nursing Students in Global Health Advocacy.
The current diverse health care environment makes it vital for nursing students to have multicultural respect and understanding. Collaborative action research can be used to engage students in the learning process. Action research addressing adolescent pregnancy in rural Paraguay involved nursing students in the research process and care delivery. Two groups of nursing students participated in two or more cycles of action research. The first cycle included identifying the problem, research development, data gathering, and interpreting results. Contributing factors to adolescent pregnancy and potential solutions were discovered. Teaching reproductive education informed the second cycle of the action research. Students created reproductive education modules and taught them to more than 700 adolescents in Paraguay. Action research provided a collaborative and engaging method to teach undergraduate nursing students about both global health advocacy and the research process. The cyclic nature of action research provides an excellent way to involve subsequent student groups. [J Nurs Educ. 2022;61(4):193-196.].


Laparoscopy versus laparotomy in the management of ectopic pregnancy with massive hemoperitoneum.
To compare the safety and feasibility of operative laparoscopy versus laparotomy in women with ruptured ectopic pregnancy and massive hemoperitoneum. In a retrospective cohort study at a university-affiliated medical center, records of women with ruptured ectopic pregnancy and massive hemoperitoneum (>800mL) were reviewed. Sixty women were diagnosed with ruptured ectopic pregnancy and massive hemoperitoneum: 48 underwent emergency laparoscopy; 12 underwent emergency laparotomy. There was no difference in hemodynamic status at presentation between the groups. Median operating time was significantly shorter in the laparoscopy group (50minutes [range, 43-63minutes] vs 60minutes [range, 60-72minutes]; P=0.01). Median intra-abdominal blood loss was significantly greater in the laparotomy group (1500mL [range, 1400-2000mL] vs 1000mL [range, 800-1200mL]; P=0.002). There was no difference between the groups regarding treatment with blood products, perioperative complications, and hospitalization period. In patients with ruptured ectopic pregnancy and massive hemoperitoneum, laparoscopy is feasible and safe, with significantly shorter operating times compared with laparotomy. While the mode of surgery should be based on the surgeon's experience and preference, the significantly lower hemoperitoneum volume associated with laparoscopy may be a reflection of shorter operating times and quicker hemorrhage control.


Risk Factors of Perinatal Asphyxia Among Newborns Delivered at Public Hospitals in Addis Ababa, Ethiopia: Case-Control Study.
Perinatal asphyxia determines the newborn's future health status and viability with risk factors yet to be completely understood. It measures the status of the healthcare delivery of an organization including antenatal, intranatal, and postnatal care. In Ethiopia, 31.6% of neonatal mortality was attributed to perinatal asphyxia. This study aimed to assess the risk factors of perinatal asphyxia. An unmatched case-control study was conducted on 213 (71 cases selected using lottery method and 142 controls systematically) subjects in Addis Ababa from November 1, 2018 to June 30, 2019. Data were collected using a structured questionnaire through face-to-face interviews, entered to Epi data version 4.4, and exported to SPSS version 25 for analysis. Logistic regression was used for analysis. Variables with p< 0.25 in bivariate analysis were taken to multivariable analysis. Statistical significance was declared at P<0.05 and findings were presented using texts and tables. A total of 210 newborns (70 cases and 140 controls) and their mothers were included with an overall response rate of 98.5%. Antepartum hemorrhage [AOR=7.17; 95% CI 1.73-29.72], low birth weight [AOR=2.87; 95% CI 1.01-8.13], preterm birth [AOR=3.4; 95% CI 1.04-11.16], caesarean section delivery [AOR=2.75; 95% CI 1.01-7.42], instrumental delivery [AOR=4.88; 95% CI 1.35-17.61], fetal distress [AOR=4.77; 95% CI 1.52-14.92] and meconium-stained amniotic fluid [AOR=9.02; 95% CI 2.96-30.24] were significantly associated with perinatal asphyxia. Hence, efforts ought to go to improve the quality of antenatal and intra-natal services.


Child care use by low-income single mothers of preschoolers born preterm versus those of preschoolers born full term.
This study describes prewelfare reform child care use by 64 primarily low-income single mothers (65.6% African American) with preschoolers (half born preterm). Forty percent used child care for more than 75% of their children's lives, 20% did when not employed. Preschool children born preterm were more likely to receive child care from nonrelatives throughout their lives than children born full term. Children with health problems used a greater number of child care arrangements. Findings suggest addressing child care issues with both employed and nonemployed mothers and adequacy of child care for children with special needs.


Environmental sound classification using temporal-frequency attention based convolutional neural network.
Environmental sound classification is one of the important issues in the audio recognition field. Compared with structured sounds such as speech and music, the time-frequency structure of environmental sounds is more complicated. In order to learn time and frequency features from Log-Mel spectrogram more effectively, a temporal-frequency attention based convolutional neural network model (TFCNN) is proposed in this paper. Firstly, an experiment that is used as motivation in proposed method is designed to verify the effect of a specific frequency band in the spectrogram on model classification. Secondly, two new attention mechanisms, temporal attention mechanism and frequency attention mechanism, are proposed. These mechanisms can focus on key frequency bands and semantic related time frames on the spectrogram to reduce the influence of background noise and irrelevant frequency bands. Then, a feature information complementarity is formed by combining these mechanisms to more accurately capture the critical time-frequency features. In such a way, the representation ability of the network model can be greatly improved. Finally, experiments on two public data sets, UrbanSound 8 K and ESC-50, demonstrate the effectiveness of the proposed method.


[Valvular heart disease: anesthesia in non-cardiac surgery].
The probability of treating patients with valvular heart disease during non-cardiac surgery increases with the age of the patient. The prevalence of valvular heart disease is approximately 2.5% and increases further in the patient group aged over 75 years old. Patients with valvular heart disease undergoing non-cardiac surgery have an increased perioperative cardiovascular risk depending on the severity of the disease. Knowledge of the hemodynamic alterations and compensation mechanisms which accompany diseases of the valve apparatus is essential for a suitable treatment of patients with such pre-existing diseases. The most common valvular heart diseases lead to volume (mitral valve insufficiency) or pressure load (aortic stenosis) of the left ventricle and in the case of mitral stenosis to a pressure load on the left atrium. Depending on the underlying disease and the type of surgery planned a corresponding choice of anesthesia procedure and medication must be made. In the present review article the pathophysiology of the relevant valvular heart diseases and the implications for perioperative anesthesia management will be presented. An individually tailored extended perioperative monitoring allows hemodynamic alterations to be rapidly recognized and adequately treated.


What proportion of initially prescribed antidepressants is still being prescribed chronically after 5 years in general practice? A longitudinal cohort analysis.
Antidepressant prescribing almost doubled in the Netherlands between 1996 and 2012, which could be accounted for by longer continuation after the first prescription. This might be problematic given a growing concern of large-scale antidepressant dependence. We aimed to assess the extent and determinants of chronic antidepressant prescribing among patient aged 18 years and older. We hypothesise a relatively large prevalence of chronic (>2 years) prescription. A longitudinal observational study based on routinely registered prescription data from general practice. 189 general practices in the Netherlands. 326 025 patients with valid prescription data for all 5 years of the study. Primary outcome measure: the number of patients (N) receiving at least four antidepressant prescriptions in 2011, as well as during each of the four subsequent years. Secondary outcome measure: the above, but specified for selective serotonin reuptake inhibitors and for tricyclic antidepressants. Antidepressants were prescribed to almost 7% of our 326 025 participants each year. They were prescribed for depression (38%), anxiety (17%), other psychological disorders (20%) and non-psychological indications (25%). Antidepressants were prescribed in all 5 years to the 42% of the population who had at least four prescriptions dispensed in 2011. Chronic prescribing was higher among women than men, for those aged 45-64 years than for those aged >65 years and for those treated for depression or anxiety than for non-psychological indications (eg, neuropathic pain). Chronic prescribing also varied markedly among general practices. Chronic antidepressant use is common for depression and for anxiety and non-psychological diagnoses. Once antidepressants have been prescribed, general practitioners and other prescribers should be aware of the risks associated with long-term use and should provide annual monitoring of the continued need for therapy.


Androgen-induced changes in rat ovarian granulosa cells in vitro.
Ovarian granulosa cells collected from small antral follicles from immature rats were cultured in McCoy's 5A medium, for 1-6 days in the presence of delta 4-androstenedione, testosterone, dihydrotestosterone, and dehydroepiandrosterone (10(-5) M and 10(-7) M). Granulosa cells examined by electron microscopy demonstrated many lipid droplets, mitochondria with tubular cristae and profiles of smooth endoplasmic reticulum, all suggestive of active metabolism in the cell. Cells cultured in androstenedione, testosterone, dihydrotestosterone and dehydroepiandrosterone produced estrogen and progesterone as measured by radioimmunoassay. By day 4, cells cultured in androgen had almost completely degenerated. The control cells acquired none of the aforementioned characteristics and survived up to beyond 6 days, at which time the experiments were terminated. This study supports the hypothesis that high concentrations of androgens in cultured granulosa cells contribute to their degeneration through altered structure, which is associated with functional change.


Higher order aberrations and retinal image quality during short-term accommodation in myopic and non-myopic children.
Despite the known associations between near work and myopia, and retinal image quality and eye growth, accommodation-induced changes in higher order aberrations (HOA's) and retinal image quality in children with different refractive errors are poorly understood. Ocular HOA's were measured using a Hartmann-Shack wavefront sensor (COAS-HD, Wavefront Sciences) in 18 myopic and 18 age- and sex-matched non-myopic children during short-term accommodation tasks (four demands of 0, 3, 6 and 9 D) presented using a Badal optometer. Eighth order Zernike polynomials were fitted across a 2.3 mm pupil diameter to determine refractive power vectors (M, J180 and J45 ) and the accommodation error, and a 4 mm pupil was used for HOA analyses. Retinal image quality was examined using the visual Strehl ratio based on the optical transfer function (VSOTF) for third to eighth radial orders only. Most refractive error group differences were observed for the 6 and 9 D demands. Myopic children underwent greater changes in with-the-rule astigmatism (J180 ), higher order and third order RMS values, primary vertical ( C 3 - 1 ) and horizontal coma ( C 3 1 ), and several other individual Zernike coefficients compared with non-myopic children (all refractive error group by demand interaction p-values of ≤0.02). Non-myopic children exhibited a greater negative shift in primary ( C 4 0 ) and positive shift in secondary spherical aberration ( C 6 0 ) (both refractive error group by demand interaction p-values of ≤0.002). The VSOTF degraded for the 6 and 9 D demands in both groups, but the myopic children underwent a greater mean (SE) reduction from 0 D of -0.274 (0.048) for the 9 D demand, compared with -0.131 (0.052) for the non-myopic children (p = 0.001). These results may have implications for the association between near work, accommodation and myopia development, particularly related to the use of short working distances during near tasks.


One step conversion of toxic beta-asarone from Acorus calamus into 1-(2,4,5-trimethoxyphenyl)-1,2-dihydroxypropane and asaronaldehyde occurring in Piper clusii.
1-(2,4,5-Trimethoxyphenyl)-1,2-dihydroxypropane (2), a natural phenylpropanoid occurring in Piper clusii, has been synthesized for the first time from toxic beta-asarone (1) of Acorus calamus with osmium tetroxide, while 1 with osmium tetroxide (catalytic amount) in presence of sodium metaperiodate furnished the asaronaldehyde (3) in high yield.


Task integration in complex, bimanual sequence learning tasks.
Sequence learning and multitasking studies have largely focused on simple motor skills, which cannot be directly transferred to the plethora of complex skills found outside of laboratory conditions. Established theories e.g. for bimanual tasks and task integration thus have to be reassessed in the context of complex motor skills. We hypothesize that under more complex conditions, task integration facilitates motor learning, impedes or suppresses effector-specific learning and can still be observed despite partial secondary task interference. We used the Ξ-apparatus to assess the learning success of six groups in a bimanual dual-task, in which we manipulated the degree of possible integration between the right-hand and the left-hand sequences. We could show that task integration positively influences the learning of these complex, bimanual skills. However, the integration impedes but not fully suppresses effector-specific learning, as we could measure reduced hand-specific learning. Task integration improves learning despite the disruptive effect of partial secondary task interference, but its mitigating effect is only effective to some extent. Overall, the results suggest that previous insights on sequential motor learning and task integration can largely also be applied to complex motor skills.


Evidence on risk factors for knee osteoarthritis in middle-older aged: a systematic review and meta analysis.
This review was made to identify the risk factors for knee osteoarthritis (KOA) in middle-older aged (≥ 40 years), and to provide the newest evidence for the prevention of KOA. Cohort study and case-control study of the risk factors of KOA was included from Pubmed, Web of Science, Ovid Technologies, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database, SinoMed from their inceptions to July 2023. Two authors independently screened the literature and extracted data. Assessment of quality was implemented according to Agency for Healthcare Research and Quality (AHRQ) and Newcastle-Ottawa Quality Assessment Scale. Meta-analysis was performed using RevMan 5.3 software. 3597 papers were identified from the seven databases and 29 papers containing 60,354 participants were included in this review. Meta-analysis was performed for 14 risk factors, and 7 of these were statistical significance (P < 0.05). The risk factors which were analyzed in this review included trauma history in knee (1.37 [95% CI 1.03-1.82], P = 0.030), body mass index (BMI) ≥ 24 kg/m2 (1.30 [95% CI 1.09-1.56], P = 0.004), gender (female) (1.04 [95% CI 1.00-1.09], P = 0.030), age ≥ 40 (1.02 [95% CI 1.01-1.03], P = 0.007), more exercise (0.75 [95% CI 0.62-0.91], P = 0.003), a high school education background (0.49 [95% CI 0.30-0.79], P = 0.003) and an university education background (0.22 [95% CI 0.06-0.86], P = 0.030). The risk factors analyzed in this review included trauma history in knee, overweight or obesity, gender (female), age ≥ 40 and the protective factors included more exercise and a high school or an university education background.


A sense of ginger fraud: prevalence and deconstruction of the China-European union supply chain.
As an important spice, ginger has been widely distributed in the Chinese and the European Union (EU) markets, the two largest trading areas, in various forms. The ginger supply chain between China and the EU is long and complex, providing opportunities for fraudsters to deceive consumers. However, limited attention has been given to food fraud in ginger, and there is a lack of research on this topic. In this review, ginger was used as an example for interpreting the fraud issues within low-priced and high-trade volume spice products. This review aims to summarize the open access information from food and food fraud databases, literature, and stakeholders about ginger fraud, and to map, deconstruct and analyse the food fraud vulnerability in the supply chain. In addition, potential testing strategies to detect ginger fraud were also discussed. The investigation of food fraud databases, a semi-structured literature review and online interviews with stakeholders revealed that adulteration is the major fraud type in ginger products. And the most vulnerable ginger products are ground ginger and finely processed ginger. The ginger supply chain from China to the EU comprises nine stages and is medium vulnerable to food fraud, both in regard to opportunities and motivational drivers. To ensure the integrity of the ginger supply chain, there is a need to apply fraud vulnerability tools in the companies of the industry. In addition, screening and confirmatory techniques based on the characteristics of ginger should be utilised for monitoring fraud issues in the supply chain.


Loss of dopaminergic neurons by the induction of inducible nitric oxide synthase and cyclooxygenase-2 via CD 40: relevance to Parkinson's disease.
A glial reaction associated with up-regulation of inflammatory molecules has been suggested to play an important role in dopaminergic neuron loss in Parkinson's disease (PD). Among inflammatory molecules, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been focused upon as key factors in the pathogenesis. However, the mechanism of how these molecules are induced in PD brains is not clearly understood. We focused on CD 40, which is expressed on neural cells and could be implicated in the neuroinflammation by inducing inflammatory molecules. We showed that both iNOS and COX-2 were up-regulated in microglia and astrocytes by CD 40 stimulation in association with a low dose of interferon-gamma (IFN-gamma) in vitro. Selective loss of dopaminergic neurons was induced by costimulation with CD 40 and IFN-gamma in mesencephalic cultures, which was protected by selective inhibitors of iNOS and/or COX-2. We also found in CD 40-stimulated astrocytes an increase of a low-affinity IgE receptor CD 23, which is known to induce iNOS expression. Together these data suggest that up-regulated iNOS and COX-2 via the CD 40 pathway may lead to dopaminergic neuron loss and may participate in the neuroinflammaory pathway of PD.


Myelination changes in the rat optic nerve after prenatal exposure to methamphetamine.
The use of psychostimulants during adolescence and early adult life has increased in recent years. It is known that these substances affect the sensory systems, and the optic nerve has been shown to be a target tissue. This work was conducted to evaluate the effects of prenatal exposure to methamphetamine (MA) on the developmental pattern of the rat optic nerve. Pregnant female rats were given 5 mg/kg body weight/day MA, s.c., in 0.9% saline from gestational days 8 to 22. The control group was injected with an isovolumetric dose of 0.9% saline. Animal model parameters, such as gestational body weight evolution, food intake and pups parameters were registered. The offspring were sacrificed at postnatal days (PND) 7, 14 and 21. Morphometric analyses were performed at light and electron microscopic levels on optic nerve cross sections; parameters measured included optic nerve diameter and area, axonal density, total number of axons and myelin thickness. Myelin basic protein (MBP) was measured by western blotting in optic nerve samples at PND14 and PND21. The animal model parameters, such as maternal and pup weight, showed no significant differences between MA and control groups. Optic nerve diameter was smaller at PND7 in the male MA group and in both male and female MA groups at PND21. The mean cross-sectional area was smaller at PND14 in the male MA group and in both male and female groups at PND21. The total number of myelinated axons did not vary between groups at any of the studied ages. The myelin thickness of the axons in MA-treated females was thinner when compared with the respective control group at PND21. No other differences were found concerning myelin thickness. There was a reduction of MBP protein expression in MA-injected females at PND14 and PND21. The combined results suggest that prenatal exposure to MA affects the myelination process.


Developmental competence of bovine oocytes after specific inhibition of MPF kinase activity: effect of estradiol supplementation and follicle size.
In the bovine, the concentration of 17beta-estradiol (E2) in the follicular fluid of the dominant follicle is high, indicating a possible role of E2 on the cytoplasmic maturation that occurs before the LH surge. The aim of this study was to investigate the role of E2 on the developmental competence of bovine oocytes originating from different sized follicles and temporarily maintained at the germinal vesicle stage with roscovitine (ROS). First, the efficiency of ROS to inhibit germinal vesicle breakdown (GVBD) in oocytes harvested from small (3-4 mm diameter) and medium (5-8 mm diameter) sized follicles was demonstrated. Next, the effect of E2 during temporary inhibition of GVBD by ROS on the subsequent nuclear maturation was evaluated. Oocytes from small and medium sized follicles were cultured in the presence of ROS, FSH and with or without E2 for 24 h. After this period, oocytes were cultured for another 24 h with FSH but without ROS and E2, after which the nuclear stages and the developmental competence of oocytes were assessed. In conclusion, it is demonstrated that exposure to E2, during temporary inhibition of the GVBD with ROS, affected neither nuclear nor cytoplasmic maturation of oocytes originating from small and medium sized follicles. It might be that in vivo, the increase of E2 during follicle growth is more related to selection of the dominant follicle than to the cytoplamsic maturation of the oocyte as such.


Hepatic veno-occlusive disease related to tacrolimus after pancreas transplantation.
Hepatic veno-occlusive disease (HVOD) describes the nonthrombotic, fibrous obliteration of the small centrilobular hepatic veins by connective tissue and centrilobular necrosis in zone 3 of the acini. Occlusion of the terminal venules of the liver might result in HVOD with the characteristic clinical findings of painful hepatomegaly, ascites, jaundice, and weight gain for more than 5% of patients. It is mainly observed after hematopoietic stem cell transplantation (SCT) and is responsible for significant morbidity and mortality. The incidence of HVOD is much lower after solid organ transplantation than after SCT and seems to differ from one organ to another. It has been sporadically reported after lung, renal, and liver transplantation, but has never been reported after pancreas transplantation. In general, HVOD is presumably attributed to azathioprine or tacrolimus used in solid organ transplantation. Here we describe a case of HVOD occurring after pancreas transplantation, in which tacrolimus might have played a causative role because complete recovery was observed after discontinuation of tacrolimus. Pancreas transplantation physicians should raise the suspicion of HVOD when a recipient presents with hepatomegaly, ascites, or jaundice.


Ultrafast proton/deuteron dynamics in KTaO3 observed with infrared pump-probe spectroscopy: Toward understanding of proton conduction mechanism in solid oxides.
Infrared pump-probe measurement for the OD stretching mode in KTaO3 has been performed. We observed the induced absorption signal corresponding to the 1-2 transition for the first time in oxide crystals in addition to the bleaching signal of the 0-1 transition. Both signals show long decay time of ∼200 ps, and the potential anharmonicity is found to be 3.6%. We also investigated temperature dependence of OH/OD absorption spectra to explore how a proton/deuteron interacts with the surrounding lattice vibrations, and identify the phonon mode which causes the potential fluctuations as a O-Ta-O bending motion. On the basis of the results obtained, we calculate the potential energy surface on which a proton/deuteron moves and discuss the proton conduction mechanism in solid oxides.


Highly Efficient Quasi-Solid-State Asymmetric Supercapacitors Based on MoS2/MWCNT and PANI/MWCNT Composite Electrodes.
Molybdenum disulfide (MoS2) and polyaniline (PANI) electrodes were decorated with multi-walled carbon nanotubes (MWCNTs) on the basis of a facial hydrothermal and in situ polymerization methods and served in the asymmetric supercapacitor (ASC). The MoS2 and MWCNTs with a mole ratio of 1:1 in MoS2|MWCNTs electrode exhibited better electrochemical properties through extensive electrochemical studies, in terms of the highest specific capacitance of 255.8 F/g at 1 A/g, low internal resistance, and notable electrochemical stability with retention of the initial specific capacitance at 91.6% after 1000 cycles. The as-prepared PANI|MWCNTs electrode also exhibited good specific capacitance of 267.5 F/g at 1 A/g and remained 97.9% capacitance retention after 1000 cycles. Then, the ASC with MoS2|MWCNTs and PANI|MWCNTs composite electrodes were assembled with polyvinyl alcohol (PVA)-Na2SO4 gel electrolyte, which displayed good electrochemical performance with the specific capacitance of 138.1 F/g at 1 A/g, and remained the energy density of 15.09 Wh/kg at a high power density of 2217.95 W/kg. This result shows that this ASC device possesses excellent electrochemical properties of high energy density and power output and thus showing a potential application prospect.


Key Focus Group Themes to Inform Weight Management Interventions in Deep South African Americans.
To understand African Americans' perceptions, barriers, and facilitators to recruitment, enrollment, adoption, maintenance, and retention in a nutrition and physical activity promotion program. Four focus groups were conducted. Two community settings located in Jackson and Hattiesburg, Mississippi. Participants (n = 28) were aged 18-50 years. Barriers and facilitators associated with healthy eating, physical activity, achieving a healthy weight, and participation in a health behavior change program. A conventional thematic content analysis approach includes data familiarization, initial code generation, initial theme generation, themes review, and team review for finalization of themes. Major themes related to health behaviors and participation in a behavior change program were identified by participants, including time constraints, costs, social support, consistency and self-efficacy, motivation for longevity and disease prevention, physical appearance, fear of injury/pain, social norms/stigma associated with outdoor physical activity, body criticism from family members, and having empathic and validating program staff support. Several social determinants of health were identified as essential considerations for promoting healthy nutrition and physical activity behaviors among African American adult Mississippians. Cultural and spiritual implications were also identified. Study insights inform policy approaches for designing culturally appropriate health behavior change programs in the Deep South.


Volumetric CT perfusion assessment of treatment response in head and neck squamous cell carcinoma: Comparison of CT perfusion parameters before and after chemoradiation therapy.
World Health Organization estimated that there were 600,000 new cases of head and neck cancers and 300,000 deaths each year worldwide. Scientific modalities to predict the treatment outcomes are not available yet. We conducted this study to (1) compare CT perfusion parameters before and after chemoradiation among patients with head and neck squamous cell carcinoma and (2) to evaluate the prognostic value of each perfusion parameter in predicting the response to chemoradiation. We conducted a prospective study among all patients with head and neck squamous cell carcinoma registered for chemoradiotherapy (CRT) at Regional Cancer Research Center, Shimla, Himachal Pradesh, India during the period June 2012 through June 2013. CTp data were acquired on a 64-slice CT scanner (Light speed VCT Xte; GE Healthcare) with 14 cm z-axis coverage using Volume Helical Shuttle (VHS) feature at baseline, on completion of 40 Gy and 66 Gy of chemoradiation. We dichotomised the treatment outcome as complete response and non-response (partial responders/stable disease/progressive disease) using RECIST 1.1 criteria. We compared all perfusion parameters at baseline, 40 Gy and 66 Gy of CRT between responders and non-responders. We dichotomised the perfusion parameters as high (>median value) and low (≤median value) to analyze association between perfusion parameters and treatment outcome. We calculated the sensitivity, specificity, predictive values, and likelihood ratios for each dichotomized perfusion parameter using Wilson Score method. We followed 24 patients (23 of them men) from start of the treatment till completion of it. All had Stage III or Stage IV of the disease. Blood flow (BF) and blood volume (BV) decreased and Mean Transit Time (MTT) increased significantly (p < 0.05) at 66 Gy among responders to CRT as compared to non-responders. Patients with high BF (>106 ml/100 g/min) at baseline were five times more likely (p = 0.004) to respond to treatment as compared to those with low BF. BF was found to be 83.3% predictive of complete response. Other perfusion parameters were not significantly predictive of outcome (p > 0.05) Combination of high BF (>106 ml/100 g/min) and low (≤47 ml/100 g/min) permeability surface (PS) was 100% predictive of response to CRT irrespective of the stage of tumor. High BF at baseline is the single best predictor of response to chemoradiaton. A combination of high BF and low PS was found to be 100% predictive of complete response irrespective of the stage of the tumor.


Chicken mucin-cross-reactive antigen.
We have previously described a chicken heterophile antigenic determinant (CHAD-1) shared by Mycobacterium smegmatis and chicken tissues. We then demonstrated that CHAD-1 is present on several chicken glycoproteins and that its immunoreactive domains are highly branched asparagine-linked oligosaccharides terminating in N-acetylglucosamine residues. In the present study, we have shown that CHAD-1 is also expressed by mucin purified to homogeneity from a soluble mucus of chicken intestine. Another antigen found on chicken mucin is a chicken mucin-cross-reactive antigen (CMCRA). Antisera to this antigen were produced by immunization of rabbits with an enriched preparation of CHAD-1 isolated from the bursa of Fabricius. These antisera were absorbed with Mycobacterium smegmatis (to block the anti-CHAD-1 antibody) and with chicken serum, and then used for immunoperoxidase staining of chicken tissue sections for CMCRA. The latter antigen was detected in most medullary cells of the bursa, in epithelial cells and Hassal's corpuscles of the thymus, and in mucus-producing cells of the intestine, esophagus, trachea, and bronchi. Using Western immunoblot analysis, we demonstrated that CMCRA is expressed by a number of polypeptides extracted from bursal lymphoid cells. These polypeptides could not be detected in extracts of thymus, spleen, peripheral blood or bone marrow mononuclear cells.


Attitudes, knowledge, and interest: preparing university students to work in an aging world.
The underlying goals of the present study were (i) to assess knowledge of and attitudes towards aging in a sample of Portuguese undergraduate students undertaking various degrees in health and welfare subjects, and (ii) to analyze the extent to which knowledge, attitudes and other factors were associated with interest in working with older adults. The study was cross-sectional in design. The sample comprised 460 Portuguese undergraduate students enrolled in degrees in nursing, social work, and psychology. They were asked to complete questionnaires and quizzes, which were analyzed using contingency tables and one way analysis of variance for inter-group comparison, and then subjected to multivariate logistic regression analysis. Significant differences emerged between groups on knowledge, attitudes towards aging and interest in working with older adults, with both nursing and social work students displaying more positive attitudes, knowledge, and interest in working with older adults, when compared with psychology students. A regression analysis indicated that attitudes, knowledge, and previous formal contact were significant predictors of interest. Interest in working with older adults was significantly related to positive attitudes, more knowledge and formal previous contact. Positive attitudes towards older adults can be promoted through interaction with faculty members and experts, knowledge acquisition about normative changes with age, and contact with healthy and impaired older adults.


Respiratory chain cysteine and methionine usage indicate a causal role for thiyl radicals in aging.
The identification of longevity-related structural adaptations in biological macromolecules may yield relevant insights into the molecular mechanisms of aging. In screening fully sequenced animal proteomes for signals associated with longevity, it was found that cysteine depletion in respiratory chain complexes was the by far strongest predictor on the amino acid usage level to co-vary with lifespan. This association was though restricted to aerobic animals, whereas anaerobic animals showed variable cysteine accumulation. By contrast, methionine accumulation, a prominent feature of mitochondrially encoded proteins affording competitive antioxidant protection, was not predictive of longevity, but rather paralleled aerobic metabolic capacity. Hence, the easily oxidized sulfur-containing amino acids cysteine (a thiol) and methionine (a thioether) show doubly diametrical behaviour in two central paradigms of respiratory oxidative stress. From this comparison, it is concluded that only the one-electron oxidation of thiols to thiyl radicals contributes to aging, whereas other forms of sulfur oxidation, especially even-electron oxidation of both thiols and thioethers, are less critically involved, presumably as their consequences may be much more easily repaired. Thiyl radicals may yet act as chain-transfer agents to entail an irreversible intramembrane cross-linking ("plastination") of some of the a priori most hydrophobic and insoluble proteins known, the respiratory chain complexes.


Evaluation of x-ray CT (EMI scan) and isotope brain studies, including radioisotope axial tomography.
A comparison is made of the results of computer-assisted X-ray tomography (EMI scan) and those of radionuclide brain scan supplemented by computer-assisted isotope tomography. The X-ray examination shows a wider range of positive diagnosis, but the radionuclide examination is complementary in the detection of supratentorial gliomas. A similar comparative value of the isotope tomogram is noted in the detection of cerebral infarcts.


Diuretic and serum electrolyte regulation potential of aqueous methanolic extract of Solanum surattense fruit validates its folkloric use in dysuria.
Solanum surattense Burm. (Solanaceae) is traditionally used for management of various ailments. The study was conducted for provision of pharmacological justification for folkloric uses of Solanum surattense in the treatment of dysuria. Rats were randomly divided into 5 groups, each of (n = 6). Aqueous methanolic fruit extract of S. surattense were also administered intraperitoneally to the rats at doses of 50, 70 and 100 mg/kg. Furosemide (10 mg/kg i.p) was used as standard drug whereas controls were given saline solution (40 mL/kg i.p). The electrolytes in urine were measured using a flame photometer whereas serum sodium, potassium, calcium, bicarbonate and blood urea nitrogen (BUN) were determined by using an automatic analyzer. Urine osmolality was assayed by the micro-osmometer. The extract S. surattense induced diuretic effects in a dose-dependent manner as compared with control. Upon administration of extract (70 and 100 mg/kg), we observed the prominent (p < 0.01) increase in the urine volume and osmolality in comparison to control group. However, plant extract (100 mg/kg) significantly increase the urinary electrolyte excretion especially calcium (p < 0.05) to that of the furosemide whereas level of magnesium remains constant. Moreover, our results showed a decrease in serum levels of sodium, potassium, calcium and blood urea nitrogen (BUN), but concentration dependent increase in bicarbonate was found in the test groups. There was no substantial change in the pH of urine samples of the extract-treated groups. These results indicate that S. surattense investigated exert its action by causing diuresis in the treatment of dysuria.


Relative and absolute bioavailability of prednisone and prednisolone after separate oral and intravenous doses.
A randomized, four-way cross-over study was conducted in eight healthy male volunteers to determine the relative and absolute bioavailability of prednisone (PN) and prednisolone (PL). PN and PL were administered as single, oral 10-mg tablet doses and as 10-mg zero-order 0.5-hour intravenous infusions. Comparable mean PN and PL maximum plasma concentrations (Cmax), times for Cmax, areas under the plasma concentration-time curves (AUC), and apparent elimination rate constants between tablet treatments demonstrated that PN and PL tablets were bioequivalent. Absolute bioavailability (F) determinations based on plasma PL concentrations were independent of which IV treatment was used as reference and indicated complete systemic availability of PL from both PN and PL tablets. However, F based on plasma PN data was contradictory. Using IV PN as reference, approximately 70% systemic availability was observed from both tablets, whereas using IV PL as reference, systemic availability was greater than unity. PN and PL are model compounds that exemplify the difficulties involved in accurately determining the relative and absolute bioavailability of substances that undergo reversible metabolism.


Surgery for atrial fibrillation: recent progress and future perspective.
Development and introduction of radiofrequency ablation devices allowed the maze procedures to be performed safely and easily, further enabling off-pump pulmonary vein isolation through a mini-thoracotomy or thoracoscope. The effects of the maze procedure include prevention of stroke and other complications related to atrial fibrillation, improved cardiac performance, and relief of symptoms. Indications for the maze procedure have been discussed on the basis of the evidence. Pulmonary vein isolation has been shown to be effective in most patients with paroxysmal atrial fibrillation and can be performed with endocardial catheter ablation and minimally invasive epicardial ablation. These two modalities should be compared in terms of the success rate, occurrence of cerebral microembolic signals, capability of additional lesions indicated for persistent or long-standing persistent atrial fibrillation, and closure of the left atrial appendage. Noncontinuous or nontransmural lines of conduction block as a result of incomplete ablation can result in recurrence of atrial fibrillation and induction of atrial tachycardia. Intraoperative verification of conduction block across the ablation lines is recommended to prevent these complications. Volume reduction of the enlarged left atrium or a boxlesion to isolate the entire posterior left atrium may be effective in patients with a dilated left atrium, but the potentially impaired atrial transport function should be considered. Mapping of active ganglionated plexi and their ablation may improve the outcome of the procedure, but the long-term effect on atrial fibrillation and autonomic nerve activities should be examined.


Development, preparation and safety testing of a Clostridium welchii type C toxoid. II. Laboratory evaluation of potency.
The results obtained with four laboratory tests on four candidate formulations of Clostridium welchii type C vaccine for use in man have been compared with clinical responses to the same vaccines. Quantal response assays in mice appeared to reflect the ranking of the four vaccines in human subjects better than did the guinea pig tests. They also enabled the potency of the vaccine preparations to be related to an existing International Reference Preparation. Mouse assays in which the animals received two spaced doses of vaccine prior to challenge yielded marginally more satisfactory results in terms of precision and reflection of human responses than did assays involving a single dose of vaccine.


Self-regulation of autoreactive kidney-infiltrating T cells in MRL-lpr nephritis.
MRL-lpr kidney-infiltrating (KI) T cell clones (CD3+, TCR alpha/beta+, B220+, CD4-, CD8-) are autoreactive, exclusively proliferate to renal tissues, and secrete interferon-gamma (IFN-gamma). We now report that IFN-gamma treatment of tubular epithelial cells (TEC) decreases their ability to induce KI T cell proliferation. The decreased ability of IFN-gamma-treated TEC to induce T cell proliferation is evident by 24 hours and can be restored by re-exposure to TEC not treated with IFN-gamma. IFN-gamma-treated TEC supernatant does not diminish KI T cell proliferation and IFN-gamma-treated TEC fixed with glutaraldehyde remain less capable of inducing KI T cell proliferation. Although we have not identified the TEC surface molecule(s) modified by IFN-gamma, neither class I, class II, ICAM-1 nor IFN-gamma bound to the surface of TEC are responsible. In conclusion, IFN-gamma induces a surface alteration(s) on TEC capable of limiting their ability to induce KI T cell proliferation. The ability of autoreactive KI T cells to release IFN-gamma represents a self-regulatory mechanism for limiting T cell expansion.


Global Access to Cardiac Surgery Centers: Distribution, Disparities, and Targets.
Global data on cardiac surgery centers are outdated and survey-based. In 1995, there were 0.7 centers per million population, ranging from one per 120,000 in North America to one per 33 million in sub-Saharan Africa. This study analyzes the contemporary distribution of cardiac surgery centers and proposes targets relative to countries' cardiovascular disease (CVD) burdens. Medical databases, gray literature, and governmental reports were used to identify the most recent post-2010 data that describe the number of centers performing cardiac surgery in each nation. The 2019 Institute for Health Metrics and Evaluation Global Burden of Disease Results Tool provided national CVD burdens. One-third of the CVD burden was assumed to be surgical. Center targets were proposed as the average or half of the average of centers per million surgical CVD patients in high-income countries. 5,111 cardiac surgery centers were identified across 230 nations and territories with available data, equaling 0.73 centers per million population. The median (interquartile range) number of centers ranged from 0 (0-0.06) per million in low-income countries to 0.75 (0-1.44) in high-income countries. Targets were 612.2 (optimistic) or 306.1 (conservative) centers per million surgical CVD incidence. In 2019, low-income, lower-middle-income, and upper-middle-income countries possessed 34.8, 149.0, and 271.9 centers per million surgical CVD incidence. Little progress has been made to increase cardiac surgery centers per population despite growing CVD burdens. Today's global cardiac surgical capacity remains insufficient, disproportionately affecting the world's poorest regions.


Magnetic dipolar interaction between correlated triplets created by singlet fission in tetracene crystals.
Singlet fission can potentially break the Shockley-Queisser efficiency limit in single-junction solar cells by splitting one photoexcited singlet exciton (S1) into two triplets (2T1) in organic semiconductors. A dark multiexciton state has been proposed as the intermediate connecting S1 to 2T1. However, the exact nature of this multiexciton state, especially how the doubly excited triplets interact, remains elusive. Here we report a quantitative study on the magnetic dipolar interaction between singlet-fission-induced correlated triplets in tetracene crystals by monitoring quantum beats relevant to the multiexciton sublevels at room temperature. The resonances of multiexciton sublevels approached by tuning an external magnetic field are observed to be avoided, which agrees well with the theoretical predictions considering a magnetic dipolar interaction of ∼ 0.008 GHz. Our work quantifies the magnetic dipolar interaction in certain organic materials and marks an important step towards understanding the underlying physics of the multiexciton state in singlet fission.


The incidence of COVID-19 in patients with metabolic syndrome and non-alcoholic steatohepatitis: A population-based study.
The novel coronavirus disease (COVID-19) emerged from China in 2019 and rapidly spread worldwide. Patients with metabolic comorbid conditions are more susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Metabolic syndrome is a constellation of interlinked metabolic risk factors that predispose patients to increased risk of complications. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and non-alcoholic steatohepatitis (NASH) is the aggressive form of NAFLD. The aim of this study is to determine the relationship between metabolic syndrome components and the risk of COVID-19. We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED-CT), we identified adults with the diagnosis of metabolic syndrome and its individual components from 1999 to 2019. We included patients with the diagnosis of COVID-19 from December 2019 to May 2020. Comorbidities known to be associated with COVID-19 and metabolic syndrome such as obesity, diabetes mellitus, dyslipidemia, smoking, male gender, African American, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether metabolic syndrome or its individual components are independently associated with the risk of COVID-19. Out of 61.4 million active adult patients in the database, 8885 (0.01%) had documented COVID-19. The cumulative incidence of COVID-19 was higher if metabolic syndrome was the primary diagnosis (0.10% vs 0.01%, OR 7.00 [6.11-8.01]). The adjusted odds (aOR) of having COVID-19 was higher in patients if they were African Americans (aOR 7.45 [7.14-7.77]), hypertensive (aOR 2.53 [2.40-2.68]), obese (aOR 2.20 [2.10-2.32]), diabetic (aOR 1.41 [1.33-1.48]), hyperlipidemic (aOR 1.70 [1.56-1.74]), or diagnosed with NASH (aOR 4.93 [4.06-6.00]). There was a slight decrease in the adjusted odds of having COVID-19 in males as compared to females (aOR 0.88 [0.84-0.92]). The incidence of COVID-19 in patients with metabolic syndrome is high. Among all comorbid metabolic conditions, NASH had the strongest association with COVID-19.


Retigabine, the specific KCNQ channel opener, blocks ectopic discharges in axotomized sensory fibres.
The M-current has been proposed as a potential target for analgesia under neuropathic pain conditions. M-currents and/or their molecular correlates, KCNQ proteins, have been demonstrated in key elements of the nociceptive system including spinal and dorsal root ganglion neurons. Here we demonstrate that retigabine, a selective KCNQ channel opener, applied at neuromatose endings modulates the excitability of axotomized fibres inhibiting ectopic discharges. Responses to mechanical and chemical stimulation were obtained from intact and previously axotomized Adelta- and C-fibres using in vitro preparations and extracellular electrophysiological recording techniques. Application of retigabine (10 microM) produced an estimated approximately 80% reduction in the number of discharges produced by mechanical and chemical stimulation of most axotomized fibres tested (24/27). The electrical threshold of stimuli applied to the neuroma was found to increase in the presence of retigabine (+17.5+/-2.3%) and to decrease in the presence of a high potassium medium (-16.5+/-3.7%). This indicates that retigabine produces a hyperpolarization and a subsequent reduction of the excitability in aberrant sensory endings. Application of XE-991 (10 microM), a KCNQ channel blocker, had no effect on responses to stimulation of the neuroma but blocked the effects of retigabine indicating a specific involvement of KCNQ channels. In contrast to the strong effects on ectopic discharges, retigabine did not change responses to stimulation recorded from intact receptors. Results indicate that KCNQ channel opening at axotomized endings may constitute a novel and selective mechanism for modulation of some neuropathic pain symptoms.


Synthesis of anti-rheumatic agent epoxyquinomicin B.
Anti-rheumatic agent (+/-)-epoxyquinomicin B was synthesized for a 22% overall yield in eight steps from commercially available 3-hydroxy-4-nitrobenzaldehyde via the intermediate quinone 6 prepared by selective phenol oxidation of 5 by use of Fremy's salt as the key step.


Formation, stabilisation and fusion of the readily releasable pool of secretory vesicles.
Calcium-triggered exocytosis of neurotransmitter or hormone-filled vesicles has developed as the main mechanism for cell-to-cell communication in animals. Consequently, in the course of evolution this form of exocytosis has been optimized for speed. Since many of the maturation processes of vesicles are intrinsically slow, the solution has been to develop a pool of vesicles that are fully matured and can be fused very rapidly upon stimulation. Vesicles in this readily releasable pool are characterized by very low release rate constants at the resting cytosolic [Ca2+] ([Ca2+]i) and very high release rate constants at stimulated [Ca2+]i. Here I review the kinetic and molecular requirements for the existence of such a pool of vesicles, focusing on chromaffin cells of the adrenal medulla. I discuss how the use of assay methods with different time resolution may lead to fundamentally different conclusions about the role of proteins in exocytosis. Finally, I review recent evidence that the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, formed between proteins residing in the vesicle and the plasma membrane, is involved in formation and stabilization of the readily releasable vesicle pool, whereas synaptotagmin, a Ca2+- and phospholipid-binding vesicular protein, is involved in setting the Ca2+ dependence of the fusion process itself. Future studies are likely to focus on the interaction between these two classes of proteins.


[Are there pseudophototropic reactions in biology? Part 3: The pseudophototropic behaviour of the cell membrane of halobacteria (author's transl)].
The behaviour of coloured membrane portions of "halobacteria" is studied with respect to spectral response and reversibility. The results are in good correlation with colour generating effects of pseudophototropic reactions. The disclosed and dicussed systems are in the range from purely synthetic to purely biological.


Effect of blood coagulation and platelet aggregation on perfusable capillaries and arterioles in ischemic and nonischemic myocardium.
The aim of this study was to determine the effect of blood coagulation and platelet aggregation on the perfusability of arterioles (19-50 micron) and capillaries in subepicardial and subendocardial ischemic and nonischemic myocardium of anesthetized open-chest rabbits. Fluorescein isothiocynate-dextran (MW 150,000) was injected intravenously to label perfusable myocardial microvessels of rabbits that were subjected to 60 min of coronary artery occlusion. Fluorescent microscopy was used to identify the perfusable vessels and an alkaline phosphatase stain was employed to locate the total microvasculature of the heart. Stereological principles were utilized to determine various morphometric parameters. About 25% of the capillaries were incapable of being perfused but virtually all arterioles were perfusable in occluded myocardium of the control group. Essentially all capillaries and arterioles were perfusable in nonoccluded myocardium. Collagen infusion produced a perfusion defect in 14% of the capillaries and arterioles in nonoccluded myocardium and in 33% of the capillaries and arterioles in occluded myocardium. Heparin, prostaglandin E1 (PGE1), or PGE1 + heparin did not prevent the perfusion defect in capillaries of occluded myocardium. It is concluded that while promotion of blood coagulation and platelet aggregation was able to produce microvessel obstruction, these hemostatic mechanisms were not primarily responsible for the capillary obstruction observed during myocardial ischemia in the rabbit heart.


Establishing an expert opinion framework for lung volume reduction in Ireland: a Delphi consensus technique.
Lung volume reduction (LVR) is an effective treatment option offered to patients with emphysema. There is no formalised LVR referral network in Ireland. A rigorous approach to agreeing and implementing a LVR referral framework in an Irish context is required. A Delphi process was used to provide a basis for a framework of multi-disciplinary teams (MDTs) which can provide LVR as a management option. A Delphi process offers a framework for understanding variations and developing a consensus from expert opinion. The aim of this study was to develop consensus on recommendations for LVR referral guidelines in an Irish context and provide a national scope based on current practice and evidence. In accordance with Guidance on Conducting and Reporting Delphi Studies, a consensus-building Delphi study was performed. Thirty-three statements informed from review of research literature were identified and presented to participants. Evaluation of the statements was performed by an expert panel using a 5-point Likert scale. ≥ 70% agreement was defined as consensus and items with a consensus rating of < 70% were revised during the process. In total, Delphi questionnaires were distributed to 18 experts with a response rate of 78% (n = 14) and a follow-up response-rate of 50% (n = 7). The expert panel in Ireland consisted of representatives from respiratory medicine, cardiothoracic surgery and allied-health professionals with expertise in COPD care. Of the initial 33 statements in five dimensions, there were consensus regarding 31 statements. The 31 statements agreed through this Delphi study clarify a coherent direction for development of a LVR framework in Ireland. The Delphi study methodology described is a useful process to reach consensus among multi-disciplinary experts.


Natural and anthropogenic sources and processes affecting water chemistry in two South Korean streams.
Acid mine drainage (AMD) in a watershed provides potential sources of pollutants for surface and subsurface waters that can deteriorate water quality. Between March and early August 2011, water samples were collected from two streams in South Korea, one dominantly draining a watershed with carbonate bedrock affected by coal mines and another draining a watershed with silicate bedrock and a relatively undisturbed catchment area. The objective of the study was to identify the sources and processes controlling water chemistry, which was dependent on bedrock and land use. In the Odae stream (OS), the stream in the silicate-dominated catchment, Ca, Na, and HCO3 were the dominant ions and total dissolved solids (TDS) was low (26.1-165 mg/L). In the Jijang stream (JS), in the carbonate-dominated watershed, TDS (224-434 mg/L) and ion concentrations were typically higher, and Ca and SO4 were the dominant ions due to carbonate weathering and oxidation of pyrite exposed at coal mines. Dual isotopic compositions of sulfate (δ(34)SSO4 and δ(18)OSO4) verified that the SO4 in JS is derived mainly from sulfide mineral oxidation in coal mines. Cl in JS was highest upstream and decreased progressively downstream, which implies that pollutants from recreational facilities in the uppermost part of the catchment are the major source governing Cl concentrations within the discharge basin. Dual isotopic compositions of nitrate (δ(15)NNO3 and δ(18)ONO3) indicated that NO3 in JS is attributable to nitrification of soil organic matter but that NO3 in OS is derived mostly from manure. Additionally, the contributions of potential anthropogenic sources to the two streams were estimated in more detail by using a plot of δ(34)SSO4 and δ(15)NNO3. This study suggests that the dual isotope approach for sulfate and nitrate is an excellent additional tool for elucidating the sources and processes controlling the water chemistry of streams draining watersheds having different lithologies and land-use patterns.


Ancestral sex-role plasticity facilitates the evolution of same-sex sexual behavior.
Recent attempts to explain the evolutionary prevalence of same-sex sexual behavior (SSB) have focused on the role of indiscriminate mating. However, in many cases, SSB may be more complex than simple mistaken identity, instead involving mutual interactions and successful pairing between partners who can detect each other's sex. Behavioral plasticity is essential for the expression of SSB in such circumstances. To test behavioral plasticity's role in the evolution of SSB, we used termites to study how females and males modify their behavior in same-sex versus heterosexual pairs. Male termites follow females in paired "tandems" before mating, and movement patterns are sexually dimorphic. Previous studies observed that adaptive same-sex tandems also occur in both sexes. Here we found that stable same-sex tandems are achieved by behavioral plasticity when one partner adopts the other sex's movements, resulting in behavioral dimorphism. Simulations based on empirically obtained parameters indicated that this socially cued plasticity contributes to pair maintenance, because dimorphic movements improve reunion success upon accidental separation. A systematic literature survey and phylogenetic comparative analysis suggest that the ancestors of modern termites lack consistent sex roles during pairing, indicating that plasticity is inherited from the ancestor. Socioenvironmental induction of ancestral behavioral potential may be of widespread importance to the expression of SSB. Our findings challenge recent arguments for a prominent role of indiscriminate mating behavior in the evolutionary origin and maintenance of SSB across diverse taxa.


Transitioning to confined spaces impacts bacterial swimming and escape response.
Symbiotic bacteria often navigate complex environments before colonizing privileged sites in their host organism. Chemical gradients are known to facilitate directional taxis of these bacteria, guiding them toward their eventual destination. However, less is known about the role of physical features in shaping the path the bacteria take and defining how they traverse a given space. The flagellated marine bacterium Vibrio fischeri, which forms a binary symbiosis with the Hawaiian bobtail squid, Euprymna scolopes, must navigate tight physical confinement during colonization, squeezing through a tissue bottleneck constricting to ∼2 μm in width on the way to its eventual home. Using microfluidic in vitro experiments, we discovered that V. fischeri cells alter their behavior upon entry into confined space, straightening their swimming paths and promoting escape from confinement. Using a computational model, we attributed this escape response to two factors: reduced directional fluctuation and a refractory period between reversals. Additional experiments in asymmetric capillary tubes confirmed that V. fischeri quickly escape from confined ends, even when drawn into the ends by chemoattraction. This avoidance was apparent down to a limit of confinement approaching the diameter of the cell itself, resulting in a balance between chemoattraction and evasion of physical confinement. Our findings demonstrate that nontrivial distributions of swimming bacteria can emerge from simple physical gradients in the level of confinement. Tight spaces may serve as an additional, crucial cue for bacteria while they navigate complex environments to enter specific habitats.


Cardioprotective effects of defibrotide in acute myocardial ischemia in the cat.
We investigated the effects of Defibrotide (D), a natural polydeoxyribonucleotide, on acute myocardial ischemia (AMI) in anesthetized cats. A permanent ligature was placed around the left anterior descending coronary artery (LAD) 12-14 mm from its origin. Ventricular fibrillation and death were exceptional and when they occurred the cats were not included in the evaluation. Pretreatment of cats with D, 32 mg Kg-1 h-1, i.v. infusion, maintained throughout the 5 h occlusion period, reduced AMI-ST segment increases and increased the diminished pressure-rate index (PRI). AMI-induced changes in lactate, ATP and CPK in ischemic tissue were prevented by D. PGI2 gave the same results as D. Atenolol prevented the loss of myocardial CPK, but had no favourable effects on lactate and ATP in ischemic tissue. The beneficial effects of D in AMI reported here could be partly attributed to its ability to enhance PGI2 release from vascular walls; D might also relieve ischemia by improvement of local tissue oxygenation, energy supplies and platelet function by its ability to deaggregate platelet clumps.


Application of DCE-US using the LI-RADS for patients with liver nodules at high risk for hepatocellular carcinoma: A preliminary study and comparison with visual interpretation.
To explore the value of dynamic contrast-enhanced ultrasound (DCE-US) for the Liver Imaging Reporting and Data System (LI-RADS). We included 220 liver nodules at high risk for hepatocellular carcinoma (HCC) from January 2019 to October 2021. Visual interpretation and DCE-US-based quantitative categories using VueBox® software were compared for consistency, nodule enhancement intensity, and washout onset following the contrast-enhanced ultrasound LI-RADS. Taking the cut-off value of the ROC curve on washout onset as the time criterion of early washout of LR-M nodules, analyzed the diagnostic performance of LR-5 for HCC and compared it to that of washout onset within 60 s. The LI-RADS visual and DCE-US interpretation results showed good consistency (Kappa = 0.730), but differed significantly in determining the LR-5 washout onset (91.2 ± 30.2 vs. 82.0 ± 32.8 s, P = 0.020) and detecting early washout (<60 s) in 196 nodules (P = 0.047). Distinguishing HCC from non-HCC malignancies had: area under the ROC curve, 0.85 (95 % confidence interval, 0.8-0.9); Youden index, 0.69; cut-off value, 48 s; sensitivity, 74.4 %; specificity, 95.0 %. When LR-M diagnosis used washout onset within 48 s, LR-5 diagnosis had sensitivity, 72.8 %; specificity, 95.0 %; positive predictive value, 98.5 %; showing a higher sensitivity than with washout onset in 60 s (62.2 %; P = 0.033). DCE-US and visual interpretations showed high consistency in LI-RADS categories but differed in assessing the washout time. According to the DCE-US interpretation, the diagnostic performance of LR-5 could be improved using washout onset of 48 s for LR-M.


Spectral studies of conformational changes induced in beta-glucuronidase by saccharo-1,4-lactone.
Ultraviolet difference spectroscopy has been used to study the binding of the transition state analog saccharo-1,4-lactone to purified rat preputial gland beta-glucuronidase. At pH 4.5 (the pH optimum), the inhibitor induces a difference spectrum indicative of a change in the environment of tryptophyl residues. Based on the magnitude of the induced difference spectrum as a quantitative measure of inhibitor binding, a titration curve for saccharo-1,4-lactone was obtained. A Scatchard plot of the titration data indicates that 4 molecules of inhibitor bind to the enzyme tetramer at a K-I of 4 times 10-7 M. The inhibitor also induces a similar difference spectrum at pH 7.5, although the binding is considerably weaker at this pH than at pH 4.5. When the native enzyme at pH 4.5 is compared with the native enzyme at pH 7.5, a difference spectrum, distinct from that of the binding of saccharo-1,4-lactone, is observed, indicating that the enzyme exists in different conformations at these pH values. The indication that tryptophyl residues are perturbed upon binding of saccharo-1,4-lactone was supported by studies carried out with N-bromosuccinimide. At pH 4.3, this reagent was found to oxidize 6 tryptophyl residues in the native enzyme but only three in the saccharo-1,4-lactone-inhibited enzyme. A spectrophotometric titration of the enzyme indicated that of the 33 tyrosyl residues per subunit, only 5 to 6 ionize at the pK expected for free phenolic groups.


Integrating Multidimensional Data Sources to Identify Genes Regulating Complex Phenotypes.
Phenotypes collected with a view to quantitative trait locus mapping can be augmented with compatible whole-transcriptome expression data and information from several other sources. These different data sources can be assembled into multidimensional network models which allow the identification of key genes potentially driving the phenotype of interest. The following chapter describes this approach using an example workflow. Several alternatives and potential limitations are discussed to aid the researcher when applying these techniques to their own work.


Representational geometry of incomplete faces in macaque face patches.
The neural code of faces has been intensively studied in the macaque face patch system. Although the majority of previous studies used complete faces as stimuli, faces are often seen partially in daily life. Here, we investigated how face-selective cells represent two types of incomplete faces: face fragments and occluded faces, with the location of the fragment/occluder and the facial features systematically varied. Contrary to popular belief, we found that the preferred face regions identified with two stimulus types are dissociated in many face cells. This dissociation can be explained by the nonlinear integration of information from different face parts and is closely related to a curved representation of face completeness in the state space, which allows a clear discrimination between different stimulus types. Furthermore, identity-related facial features are represented in a subspace orthogonal to the nonlinear dimension of face completeness, supporting a condition-general code of facial identity.


Investigation of rhodamine derivative on behavioral impairment in a double neurotoxin lesion of substantia nigra and locus coeruleus dysfunctional mice.
Although multiple mechanisms have been studied, there is still a lack of effective treatment on non-motor symptoms in Parkinson's disease (PD) patients. Therapeutic effects of 5-(4-hydroxy-3-dimethoxybenzylidene)-thiazolidinone (RD-1), one of rhodamine derivatives, on motor recovery have been previously demonstrated, but its effects on non-motor symptoms remain unclear. Herein, we explored the beneficial effects of RD-1 on PD-related non-motor symptoms and changes in synaptic plasticity in the mesencephalon. To investigate its therapeutic effects in the non-motor symptoms of Parkinsonian model, we employed male C57BL/6N mice and double injection with noradrenergic specific neurotoxin N-2-Chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride, followed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Next, we performed behavioral tests, histological analyses and immunoblotting. Our findings showed that RD-1 significantly alleviated locomotor abnormality, motor disturbance, anxiety/depression-like behavior and memory deficit. It rescued the levels of tyrosine hydroxylase in substantia nigra, and striatum. Moreover, RD-1 upregulated expression levels of α-synuclein, synapsin II, postsynaptic density 95 and vesicle-associated membrane protein 2. The restoration of synaptic function may underlie the neuroprotective effects of RD-1 in double lesioned mice, confirming its protective effect for dopaminergic neurodegeneration.


A novel method for the rapid determination of beta-amyloid toxicity on acute hippocampal slices using MTT and LDH assays.
It is difficult task to measure precisely the toxic effect of beta-amyloid (Aβ 1-42) peptides and also the protective effect of novel drug candidates against Aβ-peptides. The widely used MTT-assay in cell lines or primary cell cultures could be insensitive against Aβ-peptides. We describe here an easy and relevant method for testing Aβ 1-42 toxicity on acute hippocampal slices derived from rat. Brain slice viability in different conditions was measured using MTT and LDH assays. The concomitant use of these two assays can give detailed and relevant results on the toxic effect of Aβ 1-42 in oxygen-glucose deprived (OGD) acute brain slice model. Both assays are capable of quantifying tissue viability by measuring optical density (OD). We found that simultaneous application of OGD and Aβ 1-42 treatment induced a more intensive decrease in hippocampal slice viability than their separate effects. The use of MTT and LDH assay for quantifying brain slice viability proved to be an easy ex vivo method for investigating Aβ toxicity. Testing brain slices is more relevant in Alzheimer's Disease research than using in vitro cell cultures, due to maintenance of the three dimensional cellular network, the cell variability and intact cell connections.


Age-related deficits in the retention of memories for cued fear conditioning are reversed by galantamine treatment.
Aging has diverse effects on different behaviors and underlying neural systems. This study utilized fear conditioning to determine if aged mice have deficits in the acquisition and/or retention of memories for contextual or cued fear conditioning, and to determine if galantamine, an acetylcholinesterase (AChE) inhibitor and allosteric modulator of nicotinic acetylcholinergic receptors, would alter acquisition and/or retention of fear conditioning memories in young (2-3 months) and aged (19-20 months) C57BL/6 mice. Mice were trained with two white-noise CS (85 dB, 30 s)-footshock US (0.57 mA, 2 s) presentations. In the initial study, separate groups were tested 24, 48, or 96 h post-training. All mice were retested 1 week after the initial test. Aged mice were impaired in freezing to the CS for the 48 and 96 h train-test intervals, but not the 24-h interval. When retested 1 week after the initial test, freezing to the CS was significantly lower for all train-test intervals. No age-related deficits were found in contextual fear conditioning. In the second study, 2 mg/kg galantamine was administered to young and aged mice before fear conditioning and conditioned fear was assessed 48 h later. No age-related deficits in cued fear conditioning were seen in galantamine-treated aged mice. Thus, aged C57BL/6 mice are impaired in the long-term retention of auditory cued fear conditioning, but not the acquisition of auditory cued or contextual fear conditioning. This retention deficit for cued fear conditioning is ameliorated by treatment with the AChE inhibitor galantamine.


Contributions of parvocellular and magnocellular pathways to visual perception near the hands are not fixed, but can be dynamically altered.
Visual perception is altered near the hands, and several mechanisms have been proposed to account for this, including differences in attention and a bias toward magnocellular-preferential processing. Here we directly pitted these theories against one another in a visual search task consisting of either magnocellular- or parvocellular-preferred stimuli. Surprisingly, we found that when a large number of items are in the display, there is a parvocellular processing bias in near-hand space. Considered in the context of existing results, this indicates that hand proximity does not entail an inflexible bias toward magnocellular processing, but instead that the attentional demands of the task can dynamically alter the balance between magnocellular and parvocellular processing that accompanies hand proximity.


Seasonality of acute kidney injury phenotypes in England: an unsupervised machine learning classification study of electronic health records.
Acute Kidney Injury (AKI) is a multifactorial condition which presents a substantial burden to healthcare systems. There is limited evidence on whether it is seasonal. We sought to investigate the seasonality of AKI hospitalisations in England and use unsupervised machine learning to explore clustering of underlying comorbidities, to gain insights for future intervention. We used Hospital Episodes Statistics linked to the Clinical Practice Research Datalink to describe the overall incidence of AKI admissions between 2015 and 2019 weekly by demographic and admission characteristics. We carried out dimension reduction on 850 diagnosis codes using multiple correspondence analysis and applied k-means clustering to classify patients. We phenotype each group based on the dominant characteristics and describe the seasonality of AKI admissions by these different phenotypes. Between 2015 and 2019, weekly AKI admissions peaked in winter, with additional summer peaks related to periods of extreme heat. Winter seasonality was more evident in those diagnosed with AKI on admission. From the cluster classification we describe six phenotypes of people admitted to hospital with AKI. Among these, seasonality of AKI admissions was observed among people who we described as having a multimorbid phenotype, established risk factor phenotype, and general AKI phenotype. We demonstrate winter seasonality of AKI admissions in England, particularly among those with AKI diagnosed on admission, suggestive of community triggers. Differences in seasonality between phenotypes suggests some groups may be more likely to develop AKI as a result of these factors. This may be driven by underlying comorbidity profiles or reflect differences in uptake of seasonal interventions such as vaccines.


Relating the climate envelopes of urban tree species to their drought and thermal tolerance.
Analysing the climate envelope of plant species has been suggested as a tool to predict the vulnerability of tree species in future urban climates. However, there is little evidence that the climate envelope of a plant species directly relates to the drought and thermal tolerance of that species, at least not at the resolution required to identify or rank species vulnerability. Here, we attempted to predict drought and thermal tolerance of commonly used urban tree species using climate variables derived exclusively from open-source global occurrence data. We quantified three drought and thermal tolerance traits for 43 urban tree species in a common garden experiment: stomatal sensitivity to vapour pressure deficit, leaf water potential at the turgor loss point, and leaf thermal tolerance. We then attempted to predict each tolerance trait from variables derived from the climate envelope of each species, using occurrence data from the Global Biodiversity Information Facility. We found no strong relationships between drought and thermal tolerance traits and climatic variables. Across wide environmental gradients, plant tolerance and climate are inherently linked. But our results suggest that climate envelopes determined from species occurrence data alone may not predict drought or thermal tolerance at the resolution required to select tree species for future urban forests. We should focus on identifying the most relevant strategies and traits required to describe tolerance which in combination with climate envelope analysis should ultimately predict growth and mortality of trees in urban landscapes.


Using the GenCut core biopsy tool with the radial endobronchial ultrasound guide sheath enables a high-quality histology sample capable of programmed cell death ligand 1 (PD-L1) testing.
Radial EndoBronchial UltraSound (R-EBUS)-guided biopsies are a promising biopsy technique for pulmonary nodules suspected of lung cancer with great safety profile. Programmed cell death ligand 1 (PD-L1) testing is increasingly demanded from lung biopsies. GenCut is a novel blunt tool that can be used to obtain core biopsies. This case series explores prospective performance of the GenCut core biopsy with R-EBUS. Once Peripheral Pulmonary Lesion was located, GenCut biopsy was performed followed by conventional (forceps ± cytology brush) R-EBUS biopsies. The overall diagnostic yield for the 16 patients with a mean peripheral pulmonary lesion (PPL) size of 4.1 cm was 100% from multi-modal R-EBUS sampling. The diagnostic yield for GenCut tool alone was 13/16 (81.2%) and the ability to perform PD-L1 from GenCut was 10/16 (62.5%). There were no adverse events recorded. GenCut tool is a novel blunt instrument that can be used safely to obtain a core biopsy suitable for PD-L1 in combination with R-EBUS without compromising the high safety profile.


Fetal hemoglobin production in adult baboons by 5-azacytidine or by phenylhydrazine-induced hemolysis is associated with hypomethylation of globin gene DNA.
Nucleoside analog were used to stimulate fetal hemoglobin synthesis in baboons. Only those nucleoside analogs (5-azacytidine and 2'-deoxy-5-azacytidine) that blocked DNA methylation caused large increases in Hb F levels. DNA extracted from bone marrow samples of these animals was cleaved with MspI or HpaII restriction enzymes and analyzed by Southern blot hybridization. Results of these experiments strongly support the hypothesis that hypomethylation of CCGG sequences in the gamma-gene region is a condition of gamma-gene expression. This also applies to Hb F elevations resulting from erythropoietic stress due to phenylhydrazine-induced hemolytic anemia.


Doppler echocardiography in a healthy, non-sedated Southern Sea Lion (Otaria flavescens) - a preliminary approach about the feasibility and clinical utility.
Echocardiography is commonly used in veterinary clinical practice for many species but is not as easily applied in non-sedated marine mammals. Additionally, Doppler echocardiography provides further information on hemodynamics, estimation of cardiac output, characterization of flow patterns, and diastolic function. However, its applications in marine mammals have not been as widely explored either. The present report aimed to characterize the left ventricle structure and function of the Southern Sea Lion (Otaria flavescens) through a Doppler echocardiography study. Data were obtained from a healthy animal trained for different veterinary examination routines. This communication constitutes the first report of Doppler echocardiography with stroke volume, and cardiac output measurement in pinnipeds, and the first report of measurement of myocardial performance index in aquatic mammals. This data brought initial information about in vivo structure and function of the heart of the Southern Sea Lion that can be safely and effectively evaluated with the use of transthoracic Doppler echocardiography. Our data have both clinical and research implications for future studies evaluating diseases of the cardiopulmonary system in pinnipeds, and cardiovascular physiology investigation in diving mammals.


Immune function modulation during artificial ovarian maturation in Japanese eel (Anguilla japonica): A transcriptome profiling approach.
The Japanese eel (Anguilla japonica) experiences dramatic internal and external environmental changes during its transoceanic reproductive migrations. Here, we assess immune function changes in the primary and secondary immune organs (head kidney and spleen) of A. japonica during artificial ovarian maturation at the previtellogenic (PV), midvitellogenic (MV), and ovulating (OV) stages by transcriptome analyses. Stress responses were also assessed by determining the serum concentrations of lysozyme, alkaline phosphatase, acid phosphatase, total antioxidant capacity, and superoxide dismutase. Our results showed that together with increased serum 17β-estrogen and testosterone, lysozyme activity and antioxidant capacity were suppressed during artificial ovarian maturation. Comparisons across these developmental stages identified 60 (head kidney) and 36 (spleen) differentially expressed genes associated with the immune system. Genes related to the key activation markers of innate immune function, such as CXCL10, CXCL11, CCL20, HSP90B, MMP9, and MMP13, were upregulated and significantly enriched in the interleukin-17 signaling pathway. Adaptive immune function-related genes (IGM and MHC1) were upregulated in the head kidney from PV to MV, and their levels increased thereafter in the spleen. Moreover, a correlation between Pax5 expression and IGM expression in the spleen of MV (IGM+/Pax5+) and OV (IGM++/Pax5-) stage suggests that adaptive immune function was enhanced during ovarian maturation. To our knowledge, the present study is the first to describe transcriptome profiling of immune organs during ovarian maturation in teleost. Our findings suggest that the interleukin-17 pathway and IgM may play important roles in spawning.