Hydrogen sulfide exposure induces apoptosis and necroptosis through lncRNA3037/miR-15a/BCL2-A20 signaling in broiler trachea.
Hydrogen sulfide (H2S) is an air pollutant, has toxic effects on respiratory tract. However, the underlying mechanisms of H2S induced respiratory toxicity and the roles of long non-coding RNAs (lncRNA) and microRNA (miRNA) in this process remain poorly understood. To clear this, we investigated the change of tracheal tissue ultrastructure and the expression profiles of lncRNAs and miRNAs of chicken trachea exposed to H2S for 42 days. Results showed that H2S exposure triggered apoptosis, necroptosis, and differential expression of 16 lncRNAs and 18 miRNAs in broiler tracheas. The results of LMH cells stimulated by NaHS in vitro also showed the occurrence of apoptosis and necroptosis. LncRNA3037 is down-regulated and miR-15a is up-regulated in tracheal tissue and LMH cells under H2S exposure. Bioinformatics analysis and dual luciferase reporter system showed lncRNA3037 bound directly to miR-15a and negatively regulates each other. A20 and BCL2 are the target genes of miR-15a and negatively regulated by it. Overexpression of miR-15a caused apoptosis and necroptosis and its inhibition partially reversed apoptosis and necroptosis of LMH cells caused by NaHS stimulation and lncRNA3037 knockdown. Taken together, we concluded that H2S exposure mediates apoptosis and necroptosis through lncRNA3037/miR-15/A20-BCL2. These results provide new insights for unveiling the biological effects of H2S in vivo and in vitro.


Global prediction model for COVID-19 pandemic with the characteristics of the multiple peaks and local fluctuations.
With the spread of COVID-19, the time-series prediction of COVID-19 has become a research hotspot. Unlike previous epidemics, COVID-19 has a new pattern of long-time series, large fluctuations, and multiple peaks. Traditional dynamical models are limited to curves with short-time series, single peak, smoothness, and symmetry. Secondly, most of these models have unknown parameters, which bring greater ambiguity and uncertainty. There are still major shortcomings in the integration of multiple factors, such as human interventions, environmental factors, and transmission mechanisms. A dynamical model with only infected humans and removed humans was established. Then the process of COVID-19 spread was segmented using a local smoother. The change of infection rate at different stages was quantified using the continuous and periodic Logistic growth function to quantitatively describe the comprehensive effects of natural and human factors. Then, a non-linear variable and NO2 concentrations were introduced to qualify the number of people who have been prevented from infection through human interventions. The experiments and analysis showed the R2 of fitting for the US, UK, India, Brazil, Russia, and Germany was 0.841, 0.977, 0.974, 0.659, 0.992, and 0.753, respectively. The prediction accuracy of the US, UK, India, Brazil, Russia, and Germany in October was 0.331, 0.127, 0.112, 0.376, 0.043, and 0.445, respectively. The model can not only better describe the effects of human interventions but also better simulate the temporal evolution of COVID-19 with local fluctuations and multiple peaks, which can provide valuable assistant decision-making information.


An implementation of reinforcement learning based on spike timing dependent plasticity.
An explanatory model is developed to show how synaptic learning mechanisms modeled through spike-timing dependent plasticity (STDP) can result in long-term adaptations consistent with reinforcement learning models. In particular, the reinforcement learning model known as temporal difference (TD) learning has been used to model neuronal behavior in the orbitofrontal cortex (OFC) and ventral tegmental area (VTA) of macaque monkey during reinforcement learning. While some research has observed, empirically, a connection between STDP and TD, there has not been an explanatory model directly connecting TD to STDP. Through analysis of the learning dynamics that results from a general form of a STDP learning rule, the connection between STDP and TD is explained. We further demonstrate that a STDP learning rule drives the spike probability of a reward predicting neuronal population to a stable equilibrium. The equilibrium solution has an increasing slope where the steepness of the slope predicts the probability of the reward, similar to the results from electrophysiological recordings suggesting a different slope that predicts the value of the anticipated reward of Montague and Berns [Neuron 36(2):265-284, 2002]. This connection begins to shed light into more recent data gathered from VTA and OFC which are not well modeled by TD. We suggest that STDP provides the underlying mechanism for explaining reinforcement learning and other higher level perceptual and cognitive function.


Attenuation of AMPA receptor activity improves motor skills in a mouse model of juvenile Batten disease.
Juvenile Batten disease, caused by mutations in the CLN3 gene, is a fatal, incurable neurodegenerative disorder in children. The Cln3-loss-of-function (Cln3(Deltaex1-6)) mouse model of the disease exhibits many characteristic pathological features of the human disorder including a deficit in motor skills. Our recent findings [Kovács, A.D., Weimer, J.M., Pearce, D.A., 2006. Selectively increased sensitivity of cerebellar granule cells to AMPA receptor-mediated excitotoxicity in a mouse model of Batten disease. Neurobiol. Dis. 22, 575-585] suggested that the neurological deficit in the Cln3(Deltaex1-6) mouse model of the disease might result from an abnormally increased AMPA receptor activity in the cerebellum. Therefore, we tested if administration of low doses of an AMPA receptor antagonist, that attenuate AMPA receptor function but avoid a toxic, complete blockade of the receptor, have beneficial effects in Cln3(Deltaex1-6) mice. Here we show that attenuation of AMPA receptor activity by a single intraperitoneal injection of the non-competitive AMPA antagonist, EGIS-8332 (1 mg/kg), significantly improves the motor skills of Cln3(Deltaex1-6) mice. Our results provide a new, promising therapeutic approach for juvenile Batten disease.


Polymorphisms in the human XPD (ERCC2) gene, DNA repair capacity and cancer susceptibility: an appraisal.
Using the human XPD (ERCC2) gene as an example, we evaluate the suggestion that polymorphisms in DNA repair genes lead to decreased DNA repair capacity and to increased cancer susceptibility. This intuitively appealing idea provides the rationale for a large number of studies that have attracted much attention from scientists, clinicians and the general public. Unfortunately, most of this work presupposes that a functional effect has been established for the DNA repair gene polymorphisms under study. For XPD, there is no credible evidence for any effect on DNA repair of the two common polymorphisms leading to p.D312N and p.K751Q amino acid variations, and evolutionary analyses strongly predict that both polymorphisms are benign. Current evidence suggests no causal relationship between XPD polymorphisms, reduced DNA repair and increased cancer risk. We do not believe that more studies of the same kind will be useful. Instead, we suggest a combination of several other approaches, which up to now have been used in only a sporadic way, to examine more rigorously the possibility that phenotypic differences are associated with polymorphisms in other DNA repair genes.


Temperature changes between neighboring days and childhood asthma: a seasonal analysis in Shanghai, China.
Few evidences are available about the impact of temperature variation on childhood asthma in different seasons. This study aimed to assess the influence of temperature changes between neighboring days (TCN) on the exacerbation of asthma among children. Daily outpatient visits for childhood asthma (DOVCA) were collected from 17 main hospitals in Shanghai, China, from 2016 to 2018. A quasi-Poisson regression combined with distributed lagged nonlinear models was employed to estimate the association between TCN and asthma visits in cool or warm seasons, after controlling for short- and long-term trends, day of week, holidays, daily mean temperature, daily mean relative humidity, and air pollutants. The TCN varied from - 9.6 to 6.7 °C. The relationship between TCN and DOVCA greatly varied by season. In warm seasons, positive TCN (temperature rise) was associated with higher risks of asthma outpatient visits and negative TCN (temperature drop) was associated with lower risks; the associations were present on lag 1 day and lasted for 2 weeks; the cumulative relative risk of childhood asthma over 0 to 14 days was 1.98 (95% confidence interval: 1.42, 2.76) and 0.31 (95% confidence intervals: 0.21, 0.44) comparing a TCN of 2.5 °C (5th percentile) and - 3.2 °C (95th percentile) with 0 °C, respectively. In cool seasons, neither negative nor positive TCN showed significant risks. In conclusion, temperature rise might increase the risk of childhood asthma exacerbation and temperature drop might decrease the risks in warm seasons. There were no statistically significant influences in cool seasons.


A novel porcine gene, POT1, differentially expressed in the longissimus muscle tissues from Wujin and Large White pigs.
The mRNA differential display technique was performed to investigate the differences of gene expression in the longissimus muscle tissues from Wujin and Large White pigs. One novel gene differentially expressed was identified through quantitative real time PCR and the cDNA complete sequence was then obtained using the rapid amplification of cDNA ends (RACE) method. The nucleotide sequence of the gene is not homologous to any of the known porcine genes. The sequence prediction analysis revealed that the open reading frame of this gene encodes a protein of 507 amino acids that shares high homology with the protection of telomeres 1 isoform 4 (POT1) of human (86%)-so that this gene can be defined as swine POT1 gene. This gene is structured in 12 exons and 11 introns as revealed by computer-assisted analysis. The tissue expression analysis indicated that the swine POT1 gene is differentially expressed in tissues including muscle, heart, liver, fat, kidney, lung, pancreas and spleen. Our experiment is the first to establish the primary foundation for further research on the swine POT1 gene.


Reflections of Healthcare Experiences of African Americans With Sickle Cell Disease or Cancer: A Qualitative Study.
The experiences of African American adult patients before, during, and after acute care utilization are not well characterized for individuals with sickle cell disease (SCD) or cancer. To describe the experiences of African Americans with SCD or cancer before, during, and after hospitalization for pain control. We conducted a qualitative study among African American participants with SCD (n = 15; 11 male; mean age, 32.7 ± 10.9 years; mean pain intensity, 7.8 ± 2.6) or cancer (n = 15; 7 male; mean age, 53.7 ± 15.2 years; mean pain intensity, 4.9 ± 3.7). Participants completed demographic questions and pain intensity using PAINReportIt and responded to a 7-item open-ended interview, which was recorded and transcribed verbatim. We used content analysis to identify themes in the participants' responses. Themes identified included reason for admission, hospital experiences, and discharge expectations. Pain was the primary reason for admission for participants with SCD (n = 15) and for most participants with cancer (n = 10). Participants of both groups indicated that they experienced delayed treatment and a lack of communication. Participants with SCD also reported accusations of drug-seeking behavior, perceived mistreatment, and feeling of not being heard or believed. Participants from both groups verbalized concerns about well-being after discharge and hopeful expectations. Race-concordant participants with SCD but not with cancer communicated perceived bias from healthcare providers. Practice change interventions are needed to improve patient-provider interactions, reduce implicit bias, and increase mutual trust, as well as facilitate more effective pain control, especially for those who with SCD.


Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation.
Sequence analysis of rearranged VHDJH genes of B lineage cells from various stages of ontogeny indicates that short sequence homologies at the breakpoints of recombination contribute to V region gene assembly. Such homologies are regularly seen at DJH junctions of neonatal pre-B cells, most of which do not contain N sequences. In the same cells, but not at later developmental stages, preferential usage of the JH1 element is observed. After birth, N sequence insertion increases with time and is always more prominent at the VHD border than the DJH border. In pre-B cells from adult animals and in mature B cells, in cases where N sequences were not detectable, sequence homologies at the DJH border were found in only half of the instances. This lower incidence could be due to N sequence addition to one of the recombining DNA ends and/or cellular selection. Inspection of VHDJH junctions for N sequence insertion, sequence homologies at the DJH border and JH1 usage allows the estimation of the timepoint in ontogeny at which particular B cell subsets are seeded into the immune system. Specifically, the present data show that the cells of the Ly1 B cell subset are generated not only neonatally but also beyond the first weeks of life. However, the DJH junctions of the progenitors of chronic B cell leukemias which originate from the same B cell subset resemble those of neonatal pre-B cells, suggesting that these cells have already undergone a transforming event at this early developmental stage.


Auxin transport in developing protophloem: A case study in canalization.
Spatiotemporal cues orchestrate the development of organs and cellular differentiation in multicellular organisms. For instance, in the root apical meristem an auxin gradient patterns the transition from stem cell maintenance to transit amplification and eventual differentiation. Among the proximal tissues generated by this growth apex, the early, so-called protophloem, is the first tissue to differentiate. This observation has been linked to increased auxin activity in the developing protophloem sieve element cell files as compared to the neighboring tissues. Here we review recent progress in the characterization of the unique mechanism by which auxin canalizes its activity in the developing protophloem and fine-tunes its own transport to guide proper timing of protophloem sieve element differentiation.


Responses of Harmonia axyridis (Coleoptera: Coccinellidae) to sulfoxaflor exposure.
Harmonia axyridis is an important predator of several pest species and is part of many Integrated Pest Management (IPM) programs. To assess the risks of pesticide application to H. axyridis, we studied the effects of sulfoxaflor on H. axyridis larvae. At 72 h after treatment, the acute toxicity LR50 was 311.9476 g a. i. ha-1 by the residual contact method. This result indicated low-contact toxicity against second-instar H. axyridis larvae. The LR50 of the F1 generation decreased from 69.96 to 36.41 g a. i. ha-1 in a long-term toxicity test. The daily hazard quotient (HQ) for H. axyridis larvae lowered the safety threshold value in the first 5 d. However, the HQ values were greater than 2 during days 6-18 after sulfoxaflor treatments. We determined the No Observed Effect Application Rates of sulfoxaflor on the survival (<11.25 g a. i. ha-1), duration of larval and pupal stages (45 g a. i. ha-1), adult stage (90 g a. i. ha-1), total pre-oviposition period, adult pre-oviposition period (45 g a. i. ha-1), and reproduction (11.25 g a. i. ha-1). Pupation, adult emergence, and eggs counts of H. axyridis were reduced after sulfoxaflor treatments. The predation ability and population demography parameters were significantly impaired by higher application rates. At 90 g a. i. ha-1 or less, sulfoxaflor was slightly harmful to H. axyridis but a rate of 180 g a. i. ha-1 was moderately harmful. These results demonstrated that sulfoxaflor is harmful to H. axyridis when applied at high application rates.


Recruitment challenges and recommendations for adolescent obesity trials.
To report our experiences with recruiting overweight and obese 13- to 16-year-olds for the Loozit® weight management randomised control trial (RCT) and to identify effective strategies for recruiting adolescents from the community to a treatment trial. The Loozit RCT is a two-arm, community-based, lifestyle intervention that aims to evaluate the effect of additional therapeutic contact provided via telephone coaching and electronic communications as an adjunct to the Loozit group programme. Strategic areas that were targeted to recruit adolescents included media, schools, health professionals and community organisations. The programme aimed to recruit a cohort of 12-16 adolescents (body mass index z-score range 1.0-2.5) aged 13-16 years every 3 months over 3 years. Information regarding recruitment and eligibility to participate was initially assessed during a telephone screen. The relative cost effectiveness of recruitment strategies was determined based on recruitment rates and costs including administrative costs and research assistant time. Out of 474 enquiries, 32% resulted in an enrollment to the RCT. Newspaper articles and school newsletters accounted for nearly 60% of enquiries and enrollments and were the most cost-effective recruitment strategies. Common reasons for ineligibility for inclusion in the RCT were adolescents being too young (21%) and parents consenting but adolescents refusing to participate (17%). The most successful recruitment strategies for the Loozit RCT were local newspapers and school newsletters. Future studies should consider involving a Public Relations department and other potentially cost-effective strategies such as peer recruitment.


Reproducibility of qualitative assessment of drusen volume in eyes with age related macular degeneration.
Although an optical coherence tomography (OCT)-derived central drusen volume ≥0.03 mm3 has been found to be a risk factor for progression to late age-related macular degeneration (AMD), this parameter is not currently available on most OCT devices or acquisition protocols. The purpose of this study was to evaluate the ability of human graders to qualitatively assess drusen volume by inspection of OCT B-scans. 100 subjects (200 eyes) from the Amish Eye Study diagnosed with early or intermediate AMD underwent OCT imaging with both Cirrus OCT and Spectralis OCT. Drusen volume was automatically computed from the Cirrus OCT volumes using the Cirrus Advanced RPE Analysis software. Spectralis volume scans were reviewed by two independent, masked graders who were asked to determine whether the central drusen volume was ≥0.03 mm3. Cohen's kappa coefficients were computed to assess the agreement. After excluding 11 eyes with poor image quality and 5 eyes used for training of the graders, the remaining 184 eyes were included in this analysis. The agreement between the graders and the automated evaluation of drusen volume by the Cirrus OCT was excellent with K = 0.88 for grader 1 and K = 0.82 for grader 2. The agreement between graders was also excellent with a K = 0.88. The presence of a high central drusen volume can be assessed reliably by qualitative inspection of OCT B-scans. This approach may be useful in the assessment of risk for progression to late AMD.


[Aggressive fibromatosis of the head and neck in children (a report of three cases)].
To discuss the therapy of aggressive fibromatosis of head and neck in children. Three cases of aggressive fibromatosis of head and neck were analyzed retrospectively. Total tumor removal was achieved in all cases and the diagnosis was confirmed pathologically. No recurrence was found during follow-up. Aggressive fibromatosis is a rare, benign but locally infiltrative condition. Complete surgical removal was a chief treatment. But it was sometimes impossible in the head and neck area because of associated growth problems. Cosmic problems and facial deformity were the main obstacles of surgery.


A study of the heat-mediated phase transformations of praziquantel hydrates. Evaluation of their impact on the dissolution rate.
Comprehensive knowledge of the critical properties of the active pharmaceutical ingredients is a requirement within the modern concept of quality. Praziquantel hemihydrate (HH) and monohydrate (MH) are new solid forms of this antihelmintic agent, which have better solubility properties than the commercial anhydrous solid form (polymorph A). The thermal stability of the hydrates was evaluated, aiming to understand any possible transformation (amorphization, change to a less soluble form). Therefore, HH and MH were prepared along with the related anhydrous solid forms A and B, and characterized employing solid-state nuclear magnetic resonance, powder X-ray diffraction, mid and near infrared spectroscopy, thermal methods and the intrinsic dissolution rate. The transformations of HH and MH under thermal stress conditions were monitored through a variable temperature infrared spectroscopy approach, assisted by multivariate curve resolution with alternating least squares (MCR-ALS), finding that HH undergoes a two-step transformation (HH→B→A) to form A, whereas MH dehydrates directly into form A. This was further confirmed by conventional calorimetric methods (differential scanning calorimetry and thermogravimetry) and powder X-ray diffractometry. The impact of changes in the stressed solid forms and their dissolution rates was also assessed. Significant differences in dissolution performance were found regarding the solid forms produced as a consequence of thermally-induced dehydration.


How well can we predict native contacts in proteins based on decoy structures and their energies?
One strategy for ab initio protein structure prediction is to generate a large number of possible structures (decoys) and select the most fitting ones based on a scoring or free energy function. The conformational space of a protein is huge, and chances are rare that any heuristically generated structure will directly fall in the neighborhood of the native structure. It is desirable that, instead of being thrown away, the unfitting decoy structures can provide insights into native structures so prediction can be made progressively. First, we demonstrate that a recently parameterized physics-based effective free energy function based on the GROMOS96 force field and a generalized Born/surface area solvent model is, as several other physics-based and knowledge-based models, capable of distinguishing native structures from decoy structures for a number of widely used decoy databases. Second, we observe a substantial increase in correlations of the effective free energies with the degree of similarity between the decoys and the native structure, if the similarity is measured by the content of native inter-residue contacts in a decoy structure rather than its root-mean-square deviation from the native structure. Finally, we investigate the possibility of predicting native contacts based on the frequency of occurrence of contacts in decoy structures. For most proteins contained in the decoy databases, a meaningful amount of native contacts can be predicted based on plain frequencies of occurrence at a relatively high level of accuracy. Relative to using plain frequencies, overwhelming improvements in sensitivity of the predictions are observed for the 4_state_reduced decoy sets by applying energy-dependent weighting of decoy structures in determining the frequency. There, approximately 80% native contacts can be predicted at an accuracy of approximately 80% using energy-weighted frequencies. The sensitivity of the plain frequency approach is much lower (20% to 40%). Such improvements are, however, not observed for the other decoy databases. The rationalization and implications of the results are discussed.


Estimation of tissue protein synthesis in sheep during sustained elevation of plasma leucine concentration by intravenous infusion.
1. The fractional rate of protein synthesis (FSR) was determined in skeletal muscle, liver, rumen and cardiac muscle of wether sheep by continuous intravenous infusion of L-[4,5-3H]leucine accompanied by infusion of 0, 7.6, 15.2 or 22.8 mmol leucine/h (three sheep per treatment). FSR was calculated assuming plasma (ksp) or intracellular (ksi) leucine-specific radioactivity (SRA) was representative of the leucine precursor pool SRA for protein synthesis. 2. Plasma leucine concentration (plateau) was linearly related to leucine infusion rate, 22.8 mmol/h evoking a tenfold increase in plasma concentration. 3. Difference between plasma leucine SRA and intracellular leucine SRA in all tissues diminished as plasma leucine concentration increased. 4. There were significant differences between ksi and ksp estimates for liver and rumen in control sheep. 5. As leucine infusion rate increased, differences between ksi and ksp diminished in all tissues. With increasing leucine infusion, in liver ksi decreased and ksp was increased, in rumen ksi decreased and ksp was stable, while in cardiac and skeletal muscle ksi and ksp both increased. 6. At a leucine infusion rate of 22.8 mmol/h, mean ksp and ksi respectively were: 11 (SE 2), 13 (SE 1); liver 19 (SE 2), 21 (SE 2); cardiac muscle 3.6 (SE 0.4), 3.8 (SE 0.3); skeletal muscle 4.1 (SE 0.2), 4.5 (SE 0.5) and did not differ significantly in any tissue.


Hypodense cerebral venous sinus thrombosis on unenhanced CT: A potential pitfall. Report of a case and review of the literature.
Cerebral venous sinus thrombosis is an uncommon disorder that requires prompt diagnosis and treatment to prevent serious complications. Due to the broad spectrum of clinical presentations, patients typically undergo noncontrast CT as the first imaging study. The classical description of cerebal venous sinus thrombosis on noncontrast CT is a hyperdense thrombus within the dural venous sinus. We report an unusual case of a hypodense cerebral venous sinus thrombosis on unenhanced CT imaging. It is important for radiologists to be aware of this atypical appearance that to our knowledge has not been previously published.


High Ammonium Addition Changes the Diversity and Structure of Bacterial Communities in Temperate Wetland Soils of Northeastern China.
The soil microbiome is an important component of wetland ecosystems and plays a pivotal role in nutrient cycling and climate regulation. Nitrogen (N) addition influences the soil's microbial diversity, composition, and function by affecting the soil's nutrient status. The change in soil bacterial diversity and composition in temperate wetland ecosystems in response to high ammonium nitrogen additions remains unclear. In this study, we used high-throughput sequencing technology to study the changes of soil bacterial diversity and community structure with increasing ammonium concentrations [CK (control, 0 kg ha-1 a-1), LN (low nitrogen addition, 40 kg ha-1 a-1), and HN (high nitrogen addition, 80 kg ha-1 a-1)] at a field experimental site in the Sanjiang Plain wetland, China. Our results showed that except for soil organic carbon (SOC), other soil physicochemical parameters, i.e., soil moisture content (SMC), dissolved organic nitrogen (DON), total nitrogen (TN), pH, ammonium nitrogen (NH4+), and dissolved organic carbon (DOC), changed significantly among three ammonium nitrogen addition concentrations (p < 0.05). Compared to CK, LN did not change soil bacterial α-diversity (p > 0.05), and HN only decreased the Shannon (p < 0.05) and did not change the Chao (p > 0.05) indices of soil bacterial community. Ammonium nitrogen addition did not significantly affect the soil's bacterial community structure based on non-metric multidimensional scaling (NMDS) and PERMANOVA (ADONIS) analyses. Acidobacteriota (24.96-31.11%), Proteobacteria (16.82-26.78%), Chloroflexi (10.34-18.09%), Verrucomicrobiota (5.23-11.56%), and Actinobacteriota (5.63-8.75%) were the most abundant bacterial phyla in the soils. Nitrogen addition changed the complexity and stability of the bacterial network. SMC, NO3-, and pH were the main drivers of the bacterial community structure. These findings indicate that enhanced atmospheric nitrogen addition may have an impact on bacterial communities in soil, and this study will allow us to better understand the response of the soil microbiome in wetland ecosystems in the framework of increasing nitrogen deposition.


Subjective social status and nocturnal blood pressure dipping.
Low social status has been linked to cardiovascular disease. Subjective social status (SSS), which represents one's perceived position in a social hierarchy, has been suggested to predict health outcomes beyond objective measures of socioeconomic status. The present study examined if lower SSS is related to reduced nocturnal blood pressure (BP) dipping, a risk factor for cardiovascular disease. In this cross-sectional study, a community sample of 53 healthy adults underwent 24-h ambulatory BP monitoring. All participants provided information on SSS and objective measures of socioeconomic status (i.e., education, occupation, and income). SSS was measured in comparison to others in the country (national SSS) as well as in comparison to one's social environment (local SSS) using the German versions of the MacArthur Scales. Analyses found that participants with low local SSS exhibited attenuated nocturnal diastolic blood pressure dipping (β = 0.29, 95% CI [0.01, 0.57], p = .043) and mean arterial pressure dipping (β = 0.29, 95% CI [0.01, 0.57], p = .041). These associations remained significant after adjusting for objective socioeconomic status. No significant associations between national SSS and cardiovascular measures were observed. In conclusion, one's perceived social position in the social environment (i.e., local SSS) is associated with nocturnal BP dipping. Therefore, local SSS may be an important psychosocial factor linking social inequality and cardiovascular health.


Mapping Fifteen Trace Elements in Human Seminal Plasma and Sperm DNA.
Studies suggest a relationship between semen quality and the concentration of trace elements in serum or seminal plasma. However, trace elements may be linked to DNA and capable of altering the gene expression patterns. Thus, trace element interactions with DNA may contribute to the mechanisms for a trans-generational reproductive effect. We developed an analytical method to determine the amount of trace elements bound to the sperm DNA, and to estimate their affinity for the sperm DNA by the ratio: R = Log [metal concentration in the sperm DNA/metal concentration in seminal plasma]. We then analyzed the concentrations of 15 trace elements (Al, Cd, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Ti, V, Zn, As, Sb, and Se) in the seminal plasma and the sperm DNA in 64 normal and 30 abnormal semen specimens with Inductively Coupled Plasma/Mass Spectrometry (ICP-MS). This study showed all trace elements were detected in the seminal plasma and only metals were detected in the sperm DNA. There was no correlation between the metals' concentrations in the seminal plasma and the sperm DNA. Al had the highest affinity for DNA followed by Pb and Cd. This strong affinity is consistent with the known mutagenic effects of these metals. The lowest affinity was observed for Zn and Ti. We observed a significant increase of Al linked to the sperm DNA of patients with oligozoospermia and teratozoospermia. Al's reproductive toxicity might be due to Al linked to DNA, by altering spermatogenesis and expression patterns of genes involved in the function of reproduction.


m6A demethylase FTO renders radioresistance of nasopharyngeal carcinoma via promoting OTUB1-mediated anti-ferroptosis.
Radiotherapy is a valid treatment for nasopharyngeal carcinoma (NPC), and radioresistance is the main cause of local NPC treatment failure. However, the underlying mechanisms and valuable markers of radioresistance for NPC remain have not been established. In this study, we observed that the m6A mRNA demethylase fat mass and obesity-associated protein (FTO) was significantly upregulated in radioresistant NPC tissues and cells relative to parental radiosensitive NPC tissues and cells. FTO enhances radioresistance by repressing radiation-induced ferroptosis in NPC. Mechanistically, FTO acts as an m6A demethylase to erase the m6A modification of the OTUB1 transcript and promote the expression of OTUB1, thereby inhibiting the ferroptosis of cells induced by radiation and finally triggering the radiotherapy resistance of NPC. Furthermore, our in vivo experiment results showed that the FTO inhibitor, FB23-2, and the ferroptosis activator, erastin, altered tumor responsiveness to radiotherapy in NPC cell lines and patient-derived xenografts. Our findings reveal, for the first time, that FTO enhances NPC radiotherapy resistance by withstanding radiation-induced ferroptosis, suggesting that FTO may serve as a potential therapeutic target and valuable prognostic biomarker in patients with NPC.


Lockdown, essential sectors, and Covid-19: Lessons from Italy.
This paper investigates how economic activity impacted Covid-19 infections and all-cause mortality. To this purpose, we exploit the distribution of essential sectors, which were exempted from a national lockdown enacted in Italy during the first wave of the pandemic, across provinces and rich administrative data in a difference-in-differences framework. We find that a standard deviation increase in essential workers per built square kilometre leads to 1.1 additional daily cases and 0.32 additional daily deaths per 100,000 inhabitants. Back of the envelope calculations suggest that about one third (47,000) of the Covid-19 cases and about 13% (13,000) of deaths between March and May of 2020 can be attributed to the less stringent lockdown for these sectors. The effect is heterogeneous across sectors. Finally, we find that the local health system played a relevant role in reducing fatalities with a higher number of general practitioners and hospital beds per capita being associated with a lower mortality.


Adsorptive removal of direct azo dye from aqueous phase onto coal based sorbents: a kinetic and mechanistic study.
This communication presents the results pertaining to the investigation conducted on color removal of trisazo direct dye, C.I. Direct Brown 1:1 by adsorption onto coal based sorbents viz. charfines, lignite coal, bituminous coal and comparing results with activated carbon (Filtrasorb-400). The kinetic sorption data indicated the sorption capacity of the different coal based sorbents. The sorption interaction of direct dye on to coal based sorbents obeys first-order irreversible rate equation and activated carbon fits with the first-order reversible rate equation. Intraparticle diffusion studies revealed the dye sorption interaction was complex and intraparticle diffusion was not only the rate limiting step. Isothermal data fit well with the rearranged Langmuir adsorption model. R(L) factor revealed the favorable nature of the isotherm of the dye-coal system. Neutral solution pH yielded maximum dye color removal. Desorption and interruption studies further indicated that the coal based sorbents facilitated chemisorption in the process of dye sorption while, activated carbon resulted in physisorption interaction.


A microarray chip for label-free detection of narcotics.
A protein array chip for label-free optical detection of low molecular weight compounds has been developed. As a proof of principle, the chip is proven capable of rapidly (approximately 1 min) determining hits from aqueous cocktails composed of four common narcotics, cocaine, ecstasy, heroin, and amphetamine, using imaging surface plasmon resonance (SPR) as the detection principle. The chip is produced by injecting a mixture of antibodies and letting them self-sort and bind to narcotic analog coupled proteins already present in a predefined pattern on the supporting substrate. An indirect detection method, where antibodies are displaced from the surface upon recognition of their corresponding narcotics, is used to obtain the optical contrast and thus a detectable SPR and/or ellipsometric signal. Two types of readouts are possible from the present setup: intensity SPR images and SPR/ellipsometric sensorgrams. Positive hits were routinely obtained for analyte concentrations of 50 pg/microL and the limit of detection, without any parameter optimizations, seems to fall in the range 0.5 pg/microL (1.4 nM) for heroin, 2.5 pg/microL (8.2 nM) for cocaine, and 5 pg/microL for the other two narcotics (26 nM for ecstasy and 37 nM for amphetamine). With improved readout possibilities (sampling frequency), signal evaluation algorithms, and antibody-antigen design strategies, we believe this limit can be further improved. The chip is shown to work for many measurement cycles with excellent reproducibility. Moreover, with a more advanced fluidic system, excess injected antibodies could be collected and reused for many cycles, which could make the running costs of the system very low. The chip is in no way limited to detection of narcotics. Other low molecular weight compounds could easily be detected on the same chip. For example, trinitrotoluene detection has already been demonstrated using our chip. Possible areas of application for the system are therefore envisaged in airport and underground transport security, customs, drug interdiction, forensics, and as warning alerts on military equipment and personnel.


Sorption of roxarsone onto soils with different physicochemical properties.
Elevated roxarsone (ROX) concentrations in soils, caused by land application of ROX-bearing poultry litter, mandate investigation of ROX sorption onto soils. Equilibrium and kinetic studies of ROX sorption onto five soils were carried out to explore the relationship between sorption parameters and soil properties, and to reveal the effects of coexisting humic acid (HA), P(V), As(V), and As(III) on ROX transport. Experimental results indicated that ROX sorption reached equilibrium within 24 h, with pseudo-second order rate constants of 5.74-5.26 × 10(2) g/(mg h); film and intra-particle diffusion were the rate-limiting processes. ROX sorption to soils involved partitioning and adsorption phenomena; however, their relative contributions varied for different soils. The maximum ROX sorption varied with soil type, ranging from 0.59 to 4.12 mg/g. Results from correlation analysis and multiple linear regressions revealed that the maximum sorption capacities, partition coefficients, and desorption percentages were correlated with soil properties, especially iron content, total organic carbon, and dissolved organic carbon. ROX sorption to soils was affected more by soil pH than the initial pH of ROX-containing solutions. Carboxylic and amide functional groups were determined to be responsible for ROX sorption to soils. ROX sorption capacities decreased in the presence of HA, P(V), As(V), and As(III), indicating that ROX mobility in soils was facilitated by dissolved organic matter (DOM) and competing anions.


Wear and coating of tillage tools: A review.
Tillage tools are the main soil engaging implements facing high abrasive wear. This paper provided an overview of the research findings published in the area of wear and coating of tillage tools. Many researchers across the world have studied on the wear behavior, coating materials and methods of the tillage implements. In the previous studies coating methods and materials were used to resist the tillage tools against the wear phenomena. The effect of soil type on the wear of parts of impalements is investigated and reported in various research works. Draft force of the coated of the parts of tillage implements have also been measured and compared against the uncoated ones and presented in various publications. Many other scientists have considered and worked on the modelling of the wear of tillage tools. Several parameters such as tool geometry, soil properties including moisture content and soil texture and performance parameters of tillage tools such as forward speed and depth have been noticed in the wear modelling. The reviewed studies indicated that the wear rate of tillage implements increases with the increase of the size of sand particles in the soil. The previous investigations showed the less consumption of draft force by the coated tillage tools. This review helps those who are interested in work on the wear behavior aspects of the soil engaging implements and the coating of soil tillage tools.


Assessment of acute, 14-day, and 13-week repeated oral dose toxicity of Tiglium seed extract in rats.
Seed of mature Croton tiglium Linne, also known as Tiglium seed (TS), has been widely used as a natural product due to its several health beneficial properties including anti-tumor and antifungal activities. Despite its ethnomedicinal beneficial properties, toxicological information regarding TS extract, especially its long-term toxicity, is currently limited. Therefore, the objective of the present study was to evaluate acute and subchronic toxicity of TS extract in rats after oral administration following test guidelines of the Organization for Economic Cooperation and Development (OECD). Toxicological properties of TS extract were evaluated by toxicity assays to determine its single-dose acute toxicity (125, 250, 500, 1000, or 2000 mg/kg), 14-day repeated-dose toxicity (125, 250, 500, 1000, or 2000 mg/kg) and 13-week repeated-dose toxicity (31.25, 62.5, 125, 250, and 500 mg/kg) in Sprague-Dawley rats and F344 rats. Hematological, serum biochemical, and histopathological parameters were analyzed to determine its median lethal dose (LD50) and no-observed-adverse-effect-level (NOAEL). Oral single dose up to 2000 mg/kg of TS extract resulted in no mortalities or abnormal clinical signs. In 13-week toxicity study, TS extract exhibited no dose-related changes (mortality, body weight, food/water consumption, hematology, clinical biochemistry, organ weight, or histopathology) at dose up to 500 mg/kg, the highest dosage level suggested based on 14-day repeat-dose oral toxicity study. Acute oral LD50 of TS extract in rats was estimated to be greater than 2000 mg/kg. NOAEL of TS extract administered orally was determined to be 500 mg/kg/day in both male and female rats. Results from these acute and subchronic toxicity assessments of TS extract under Good Laboratory Practice regulations indicate that TS extract appears to be safe for human consumption.


Experience of Time and Subjective Age When Facing a Limited Lifetime: The Case of Older Adults with Advanced Cancer.
We addressed two questions: (1) Does advanced cancer in later life affect a person's awareness of time and their subjective age? (2) Are awareness of time and subjective age associated with distress, perceived quality of life, and depression? We assessed patients suffering terminal cancer (OAC, n = 91) and older adults free of any life-threatening disease (OA, n = 89), all subjects being aged 50 years or older. Older adults with advanced cancer perceived time more strongly as being a finite resource and felt significantly older than OA controls. Feeling younger was meaningfully related with better quality of life and less distress. In the OA group, feeling younger was also associated to reduced depression. Perceiving time as a finite resource was related to higher quality of life in the OA group. Major indicators of an older person's awareness of time and subjective aging differ between those being confronted with advanced cancer versus controls.


Research priorities relating to the debate on assisted dying: what do we still need to know? Results of a modified Delphi technique.
To identify the main areas of uncertainty and subsequent research priorities to inform the ongoing debate around assisted dying. Two-round electronic modified Delphi consultation with experts and interested bodies. 110 groups and individuals interested in the subject of end-of-life care and/or assisted dying were approached to participate. Respondents included health and social care professionals, researchers, campaigners, patients and carers predominantly based in the UK. In the first round, the respondents were asked to propose high-priority research questions related to the topic of assisted dying. The collected research questions were then deduplicated and presented to all respondents in a second round in which they could rate each question in terms of importance. 24% and 26% of participants responded to the first and second rounds, respectively. Respondents suggested 85 unique research questions in the first round. These were grouped by theme and rated in terms of importance in the second round. Emergent themes were as follows: palliative care/symptom control; patient characteristics, experiences and decisions; families and carers; society and the general public; arguments for and against assisted dying; international experiences/analysis of existing national data; suicide; mental health, psychological and psychosocial considerations; comorbidities; the role of clinicians; environment and external influences; broader topics incorporating assisted dying; and moral, ethical and legal issues. 10 of the 85 proposed questions were rated as being important (≥7/10) by at least 50% of respondents. Research questions with the highest levels of consensus were predominantly concerned with understanding how and why people make end-of-life decisions, and which factors influence those decisions. Dissemination of these findings alongside a focused examination of the existing literature may be the most effective way to add evidence to the ongoing debate around assisted dying.


Junctional Neural Tube Defect (JNTD): A Rare and Relatively New Spinal Dysraphic Malformation.
Junctional neurulation completes the sequential embryological processes of primary and secondary neurulation as the intermediary step linking the end of primary neurulation and the beginning of secondary neurulation. Its exact molecular process is a matter of ongoing scientific debate. Abnormality of junctional neurulation-junctional neural tube defect (JNTD)-was first described in 2017 based on a series of three patients who displayed a well-formed secondary neural tube, the conus, that is physically separated by a fair distance from its companion primary neural tube and functionally disconnected from rostral corticospinal control. Several other cases conforming to this bizarre neural tube arrangement have since appeared in the literature, reinforcing the validity of this entity. The clinical, neuroimaging, and electrophysiological features of JNTD, as well as the hypothesis of its embryogenetic mechanism, will be described in this chapter.


Assessment of driving after stroke--a pluridisciplinary task.
The aim of the study was to analyze the assessment procedure and identify predictors for the team decision when assessing fitness to drive a car after stroke. The material used was a retrospective data set with 200 stroke clients from Queen Elisabeth's Foundation Mobility Centre at Banstead UK. Fifty-four percent of clients were considered fit to continue driving where 9% could resume driving after car adaptation and training. Important factors for the outcome were vision (acuity and field), neuropsychological functions (divided attention), and track and/or on road test (reaction time, anticipation, speed, and positioning). Cognitive impairment was the main problem in those who failed the driving test and judged not fit for continued driving. Car adaptation, mainly comprising infrared transmitted secondary controls together with automatic transmission was recommended in 35% of the cases. The contribution of different specialist groups appears to be necessary for an effective evaluation, but the assessment procedure can be done more cost-effectively by dividing it into two separate parts and removing certain subtests. The in-car track test is an important part of the assessment procedure with a high face validity and could in many cases make it unnecessary to perform in-traffic tests with unsafe drivers. Car adaptation is often necessary for a client with pronounced hemi-paresis and a full road test can for those only be performed after training the use of car controls.


Fast conjugate phase image reconstruction based on a Chebyshev approximation to correct for B0 field inhomogeneity and concomitant gradients.
Off-resonance effects can cause image blurring in spiral scanning and various forms of image degradation in other MRI methods. Off-resonance effects can be caused by both B0 inhomogeneity and concomitant gradient fields. Previously developed off-resonance correction methods focus on the correction of a single source of off-resonance. This work introduces a computationally efficient method of correcting for B0 inhomogeneity and concomitant gradients simultaneously. The method is a fast alternative to conjugate phase reconstruction, with the off-resonance phase term approximated by Chebyshev polynomials. The proposed algorithm is well suited for semiautomatic off-resonance correction, which works well even with an inaccurate or low-resolution field map. The proposed algorithm is demonstrated using phantom and in vivo data sets acquired by spiral scanning. Semiautomatic off-resonance correction alone is shown to provide a moderate amount of correction for concomitant gradient field effects, in addition to B0 imhomogeneity effects. However, better correction is provided by the proposed combined method. The best results were produced using the semiautomatic version of the proposed combined method.


Preoperative determination of the level of spinal cord lesions from the killed end potential.
To determine preoperatively the level of lesions in acute cervical cord injury, the killed end potential of the spinal cord was recorded with a pair of electrodes placed in the spinal epidural space, one initially being placed rostrally to the lesions for obtaining recordings and the other placed caudally to the lesions for stimulation. The level associated with the largest killed end potential was clearly determined without much difficulty, with sequential recordings on stepwise withdrawal of the recording electrode, in four of five cases investigated. In two cases subjected to surgery, the recording electrode left in place at the level associated with the largest killed end potential was found to be located at, or a few millimeters below, the center of the lesions. This demonstrates the preoperative localizing value of the killed end potential for determining the level of lesions responsible for myelopathy.


The persistence of adolescent binge drinking into adulthood: findings from a 15-year prospective cohort study.
To examine the prevalence of binge drinking in adolescence and its persistence into adulthood in an Australian cohort. 15-year prospective cohort study. Victoria, Australia. 1943 adolescents were recruited from secondary schools at age 14-15 years. Levels of past-week 'binge' drinking (5+ standard drinks on a day, each 10 g alcohol) and 'heavy binge' drinking (20+ standard drinks on a day for males, 11+ for females) were assessed during six adolescent waves, and across three adult waves up to age 29 years. Half of the males (52%) and a third of the females (34%) reported past-week adolescent binge drinking. 90% of male and 70% of female adolescent-onset binge drinkers continued to binge in young adulthood; 70% of males and 48% of females who were not adolescent-onset binge drinkers reported young adult binge drinking. Past-week heavy bingeing was less common in adolescence than adulthood. Overall, 35% of the sample (95% CI 33% to 38%) reported past-week binge drinking in adolescence and young adulthood and one-third (33%; 30% to 35%) first reported binge drinking in young adulthood; only 7% of the sample (6-8%) had binge drinking in adolescence but not young adulthood. 'Heavy binge' drinking occurred in adolescence and young adulthood for 9% (8% to 10%); 8% (7% to 10%) reported it in adolescence but no longer in young adulthood; and 24% (22% to 26%) began 'heavy binge' drinking in young adulthood. Among adolescent binge drinkers (n=821), young adult binge and heavy binge drinking were predicted by being male, adolescent antisocial behaviour and adverse consequences of drinking in adolescence. Binge alcohol use is common and persistent among young Australians. Efforts to prevent the onset of binge drinking during adolescence may substantially reduce harmful patterns of alcohol use in young adulthood.


Analysis of COVID-19 mortality in patients with comorbidities in Côte d'Ivoire.
Although COVID-19 has spread in Côte d'Ivoire, there is no report that summarizes the comorbidities of COVID-19 death cases. To verify the types and prevalence of commodities associated with recorded COVID-19 deaths compared with the general adult population in Côte d'Ivoire. Data on the comorbidities of COVID-19 deaths and the country's disease structure were collected from official government reports and WHO's reports. Among 67 patients studied, the biggest age group was 60-69 years old with 23 people (34%). Fifty-four patients (81%) had non-communicable diseases (NCDs) as comorbidities. The prevalence ratio between COVID-19 deaths and general adult population was 8.96 [95% Confidence Interval: 6.86-11.68] for diabetes, 1.74 [1.27-2.37] for hypertension, and 2.16 [1.32-3.51] for obesity. To reduce the risk of death from COVID-19 in Côte d'Ivoire, focused infection prevention measures for elderly and diabetic patients are needed.


Can Montgomery tubercles impact aesthetic 3D nipple-areolar complex tattooing? An anatomical, quantitative analysis of breast cancer patients.
We aimed to establish a relationship between the amount of Montgomery tubercles (MTs) per nipple-areolar complex (NAC) given patient characteristics such as age, BMI, menopausal status, race/ethnicity, and NAC size to better inform current 3D NAC tattooing practices. Preoperative photographs of patients pursuing breast reconstruction after mastectomy in 2010 through 2018 were reviewed. The number of MTs on each native NAC was quantified. The impact of patient factors on the quantity of MTs was evaluated via Pearson correlation and bivariate analyses. Two hundred and eleven patients (399 breasts) were reviewed. On average, patients had 5.0 ± 5.2 MTs (range, 0-25 MTs). Number of MTs did not correlate with patient age, BMI, or NAC size. Premenopausal females were more likely than postmenopausal females to have a greater number of MTs per breast (p-value = 0.0183). Postmastectomy patients desiring a more "youthful" NAC may consider additional MTs when pursuing 3D NAC tattooing.


Impact of tumor-associated syrinx on outcomes following resection of primary ependymomas of the spinal cord.
To interrogate the association of tumor-associated syrinxes with postoperative neurological and oncological outcomes in patients surgically treated for WHO grade 2 spinal ependymomas. Adults treated for primary spinal intramedullary ependymomas between 2000 and 2020 were identified and data were gathered on preoperative neurological exam, radiographic characteristics, operative details, and postoperative neurological outcome. Neurological status was graded on the modified McCormick Scale (MMS). Neurological worsening immediately postoperatively and at last follow-up were defined by ≥ 1 MMS grade deterioration. Decision-tree analyses were also performed to identify independent predictors of new neurological deficits. Seventy patients were identified; mean age 45.4 ± 12.7; 60% male. Forty-eight patients (68.6%) had tumor-associated syrinxes, were more common among males (68.8%) and cervical lesions (68.8 vs. 31.8%; P = 0.005). Postoperatively patients with syrinxes had better MMS (P = 0.035) and were less likely to require a gait aid (39.6 vs. 81.8; P = 0.002). This latter difference persisted to last follow-up (22.9 vs. 59.1%; P = 0.006). On decision-tree analysis the strongest predictors of long-term neurological worsening were advanced age (≥ 63 years) and worse baseline neurological function. Worsened neurological status in the immediate postoperative period was best predicted by thoracic localization, the presence of a hemosiderin cap, and longer craniocaudal extension. For spinal ependymomas, tumor-associated syrinxes may portend decreased risk for immediate postoperative neurologic deficits but do not predict long-term neurological outcomes (MMS) or odds of successful gross total resection. Thoracic localization appears to best predict new immediate postoperative deficits, and worse baseline neurological function and advanced age best predict long-term deficits.


Pore Water Collection, Analysis and Evolution: The Need for Standardization.
Investigating the ecological impacts of contaminants released into the environment requires integration of multiple lines of evidence. Collection and analysis of interstitial water is an often-used line of evidence for developing benthic exposure estimates in aquatic ecosystems. It is a well-established principle that chemical and toxicity data on interstitial water samples should represent in-situ conditions; i.e., sample integrity must be maintained throughout the sample collection process to avoid alteration of the in-situ geochemical conditions. Unfortunately, collection and processing of pore water is not standardized to address possible geochemical transformations introduced by atmospheric exposure. Furthermore, there are no suitable benchmarks (ecological or human health) against which to evaluate adverse effects from chemicals in pore water; i.e., empirical data is lacking on the toxicity of inorganic contaminants in sediment interstitial water. It is clear that pore water data is best evaluated by considering the bioavailability of trace elements and the partitioning of contaminants between the aqueous and solid phases. It is also evident that there is a need for sediment researchers and regulatory agencies to collaborate in developing a standardized approach for sediment/pore water collection and data evaluation. Without such guidelines, the number of different pore water collection and extraction techniques will continue to expand, and investigators will continue to evaluate potentially questionable data by comparison to inappropriate criteria.


Discrimination and Identification of a Third Formant Frequency Cue to Place of Articulation by Young Children and Adults.
Typically-developing children, 4 to 6 years of age, and adults participated in discrimination and identification speech perception tasks using a synthetic consonant-vowel continuum ranging from /da/ to /ga/. The seven-step synthetic /da/-/ga/ continuum was created by adjusting the first 40 ms of the third formant frequency transition. For the discrimination task, listeners participated in a Change/No-Change paradigm with four different stimuli compared to the endpoint-1 /da/ token. For the identification task, listeners labeled each token along the /da/-/ga/ continuum as either "DA" or "GA." Results of the discrimination experiment showed that sensitivity to the third-formant transition cue improved for the adult listeners as the stimulus contrast increased, whereas the performance of the children remained poor across all stimulus comparisons. Results of the identification experiment support previous hypotheses of age-related differences in phonetic categorization. Results have implications for normative data on identification and discrimination tasks. These norms provide a metric against which children with auditory-based speech sound disorders can be compared. Furthermore, the results provide some insight into the developmental nature of categorical and non-categorical speech perception.


In vivo 3T spiral imaging based multi-slice T(1rho) mapping of knee cartilage in osteoarthritis.
T(1rho) describes the spin-lattice relaxation in the rotating frame and has been proposed for detecting damage to the cartilage collagen-proteoglycan matrix in osteoarthritis. In this study, a multi-slice T(1rho) imaging method for knee cartilage was developed using spin-lock techniques and a spiral imaging sequence. The adverse effect of T(1) regrowth during the multi-slice acquisition was eliminated by RF cycling. Agarose phantoms with different concentrations, 10 healthy volunteers, and 9 osteoarthritis patients were scanned at 3T. T(1rho) values decreased as agarose concentration increased. T(1rho) values obtained with imaging methods were compared with those obtained with spectroscopic methods. T(1rho) values obtained during multi-slice acquisition were validated with those obtained in a single slice acquisition. Reproducibility was assessed using the average coefficient of variation of median T(1rho), which was 0.68% in phantoms and 4.8% in healthy volunteers. There was a significant difference (P = 0.002) in the average T(1rho) within patellar and femoral cartilage between controls (45.04 +/- 2.59 ms) and osteoarthritis patients (53.06 +/- 4.60 ms). A significant correlation was found between T(1rho) and T(2); however, the difference of T(2) was not significant between controls and osteoarthritis patients. The results suggest that T(1rho) relaxation times may be a promising clinical tool for osteoarthritis detection and treatment monitoring.


Rats with chronic spinal cord transection as a possible model for the at-level pain of paraplegic patients.
Patients with complete spinal cord injury (SCI) often suffer from chronic pain which is perceived around the segment of the lesion. The present study tests the hypothesis that chronic SCI pain is due to pathophysiological neuronal activity in the spinal segment just rostral to the SCI. In an animal model with complete chronic SCI, the impulse activity of single dorsal horn neurones was recorded in the segment rostral to the lesion. Following SCI, the neurones exhibited a higher background activity. Some neurones showed an abnormal type of activity which was not present under control conditions. The results support the hypothesis that increased and altered background activity just rostral to the lesion contributes to chronic at-level pain of paraplegic patients.


Cloning and characterisation of a putative ST2L homologue from Atlantic salmon (Salmo salar).
The ST2L receptor is a member of the interleukin-1 (IL-1) receptor family and has previously been cloned from human, mouse, rat and chicken. This orphan receptor has no known physiological role but has been implicated in T helper cell type 2 effector function. We describe in this report the cloning and characterisation of a cDNA encoding a homologue of ST2L in Atlantic salmon (Salmo salar). The salmon ST2L cDNA is 2364bp in length and has an open reading frame encoding a polypeptide of 582 amino acids. Similar to other members of the IL-1 receptor (IL-1R) family, the predicted protein has a potential signal peptide, extracellular immunoglobulin-like domains, a short transmembrane region and a characteristic cytoplasmic Toll-IL-1R domain. The predicted protein shows 33% identity and 44% similarity to the chicken ST2L homologue. Phylogenetic analyses cluster the putative salmon ST2L with the chicken and the mammalian ST2L homologues, away from the other members of the IL-1R family. Salmon ST2L is constitutively expressed in brain, white and red blood cells, head kidney, liver, gills and muscle, with highest level of expression in spleen. In vivo stimulation of salmon with lipopolysaccaride does not appear to have a significant effect on expression of the ST2L homologue.


A reevaluation of the genus Malassezia by means of genome comparison.
Results of a study of the genus Malassezia on the basis of genome characters confirm that two species should be maintained, M. furfur and M. pachydermatis. The two forms associated with skin disease, frequently referred to as Pityrosporum orbiculare and P. ovale, were found to be synonymous, the name M. furfur having priority. Malassezia pachydermatis, hitherto regarded as a strictly zoophilic species, may also be found on humans.


Effect of glucagon-like peptide-1 on beta- and alpha-cell function in isolated islet and whole pancreas transplant recipients.
Glucose-dependent insulin secretion is often impaired after islet transplantation where reduced beta-cell secretory capacity indicates a low functional beta-cell mass. We sought to determine whether glucagon-like peptide-1 (GLP-1) enhanced glucose-dependent insulin secretion and glucagon suppression in islet recipients, and whether GLP-1 effects were dependent on functional beta-cell mass by simultaneously studying recipients of whole pancreas transplants. The study was performed in a clinical and translational research center. Five intraportal islet and six portally drained pancreas transplant recipients participated in the study. Subjects underwent glucose-potentiated arginine testing with GLP-1 (1.5 pmol . kg(-1) . min(-1)) or placebo infused on alternate randomized occasions, with 5 g arginine injected under basal and hyperglycemic clamp conditions. Basal glucose was lower with increases in insulin and decreases in glucagon during GLP-1 vs. placebo in both groups. During the hyperglycemic clamp, a significantly greater glucose infusion rate was required with GLP-1 vs. placebo in both groups (P < 0.05), an effect more pronounced in the pancreas vs. islet group (P < 0.01). The increased glucose infusion rate was associated with significant increases in second-phase insulin secretion in both groups (P < 0.05) that also tended to be greater in the pancreas vs. islet group (P = 0.08), whereas glucagon was equivalently suppressed by the hyperglycemic clamp during GLP-1 and placebo infusions in both groups. The GLP-1-induced increase in second-phase insulin correlated with the beta-cell secretory capacity (P < 0.001). The proinsulin secretory ratio (PISR) during glucose-potentiated arginine was significantly greater with GLP-1 vs. placebo infusion in both groups (P < 0.05). GLP-1 induced enhancement of glucose-dependent insulin secretion, but not glucagon suppression, in islet and pancreas transplant recipients, an effect dependent on the functional beta-cell mass that may be associated with depletion of mature beta-cell secretory granules.


Erratum: Fluro-deoxygenase-positron emission tomography/computed tomography in hard metal lung disease.
[This corrects the article on p. 480 in vol. 32, PMID: 26628763.].


Determination of the mechanism(s) for the inclusion of arsenate, vanadate, or molybdate anions into hydrotalcites with variable cationic ratio.
Hydrotalcites with cationic ratios of 2:1, 3:1, and 4:1 were synthesised using the co-precipitation method. The mechanism of inclusion of arsenate, vanadate, and molybdate into these structures is investigated using the combination of X-ray diffraction, Raman spectroscopy, and thermal analysis. Results show that hydrotalcites with cationic ratios of 3:1 are thermally more stable then the 2:1 and 4:1 structures. The increase in thermal stability of the 3:1 hydrotalcite structures is understood to be due to the intercalation of arsenate, vanadate, or molybdate, by an increase in hydrogen bonds associated with the intercalated anion. The 3:1 vanadate hydrotalcite is the most thermally stable hydrotalcite investigated. It is observed that the predominant mechanism for inclusion of the three anionic species is adsorption for 2:1 and 4:1 hydrotalcites, and intercalation for the 3:1 hydrotalcite structures. The intercalation of arsenate, vanadate, and molybdate into the hydrotalcite structure increased the interlayer distance of the hydrotalcite by 0.14, 0.13, and 0.26 A, respectively.


A revision of the genus Belciana Walker, 1862 with description of three new species (Lepidoptera, Noctuidae: Pantheinae) from East and South East Asia. Revision of Pantheinae, contribution XII.
The Oriental Pantheinae genus Belciana Walker, 1862 is revised. Three new species, B. hreblayi sp. n., B. sulawesiana sp. n., B. pinratanai sp. n., from Taiwan, Indonesia and Thailand, are described. Five new combinations in the genus Diphteroides Bethune-Baker, 1906 are proposed: Diphteroides caerulea (Hampson, 1926) comb. n., D. habroscia (Prout, 1924) comb. n., D. patricolor (Prout, 1924) comb. n., D. serrata Bethune-Baker, 1906, D. subserrata (Prout, 1924) comb. n. and D. sophronia (Prout, 1924) comb. n. The extensive diagnoses of known species of Belciana are given. The imagines, male and female genitalia are illustrated. The checklist of the genus Belciana in East Asia is presented.


4Ei-10 interdiction of oncogenic cap-mediated translation as therapy for non-small cell lung cancer.
In order to suppress 5' cap-mediated translation a highly available inhibitor of the interaction between the 5' mRNA cap and the eIF4E complex has been developed. 4Ei-10 is a member of the class of ProTide compounds and has elevated membrane permeability and is a strong active chemical antagonist for eIF4E. Once taken up by cells it is converted by anchimeric activation of the lipophilic 2-(methylthio) ethyl protecting group and after that Hint1 P-N bond cleavage to N7-(p-chlorophenoxyethyl) guanosine 5'-monophosphate (7-Cl-Ph-Ethyl-GMP). Using this powerful interaction, it has been demonstrated that 4Ei-10 inhibits non-small cell lung cancer (NSCLC) cell growth. In addition, treatment of NSCLC cells with 4Ei-10 results in suppression of translation and diminished expression of a cohort of cellular proteins important to maintaining the malignant phenotype and resisting apoptosis such as Bcl-2, survivin, and ornithine decarboxylase (ODC). Finally, as a result of targeting the translation of anti-apoptotic proteins, NSCLC cells are synergized to be more sensitive to the existing anti-neoplastic treatment gemcitabine currently used in NSCLC therapy.


Virtual colonoscopy using oral contrast compared with colonoscopy for the detection of patients with colorectal polyps.
Virtual colonoscopy using abdominal spiral computed tomography scanning allows total colonic evaluation with minimal invasiveness. Two-dimensional images and selective 3-dimensional images of the colon are used to detect colorectal lesions. This trial used conventional colonoscopy with segmental unblinding to determine the ability of virtual colonoscopy to identify patients with colorectal lesions who need conventional colonoscopy. We studied 205 patients with virtual colonoscopy using oral iodinated contrast preceding conventional colonoscopy. Colonic lavage was achieved with an oral sodium phosphosoda preparation and colonic distention with a carbon dioxide electronic insufflator. The overall sensitivity and specificity of virtual colonoscopy in identifying patients with colorectal lesions was 61.8% and 70.7%, respectively. Virtual colonoscopy was more accurate in identifying patients with lesions >/=6 mm (sensitivity 84.4% and specificity 83.1%) and those with lesions >/=10 mm (sensitivity 90% and specificity 94.6%). The negative predictive value of virtual colonoscopy was 95% for a 6-mm cutoff size and 98.9% for a 10-mm cutoff. Using a 10-mm cutoff, virtual colonoscopy precludes the need for conventional colonoscopy in 86% of patients with a 1% false-negative rate (68% with a 3.4% false-negative rate when using a 6-mm cutoff). Virtual colonoscopy has a high sensitivity and specificity for detecting patients with significant colorectal lesions. Its high negative predictive value may help reduce the number of negative screening colonoscopies. Further studies are needed to determine what lesion cutoff size is clinically acceptable and the appropriate interval time for repeat virtual colonoscopy when it detects lesions below this cutoff size.


Abnormal endogenous amino acid release in brain slices from vitamin B-6 restricted neonatal rats.
The basal and potassium-evoked efflux of glutamate, glycine, taurine, and gamma-aminobutyric acid (GABA) was measured in brain slices from vitamin B-6 restricted and sufficient 14-day-old rats. The results indicate a reduced level of basal glutamate, taurine, and GABA efflux in hippocampal slices and taurine and GABA in cortical slices from vitamin B-6 restricted animals. In the presence of depolarizing potassium concentrations, there was a reduced level of GABA efflux in hippocampal and cortical slices, and a marked reduction in the release of glutamate in cortical slices from B-6 restricted rats. The abnormalities in the secretion process of these neuroactive amino acids may be related to the neurological sequelae associated with neonatal vitamin B-6 restriction.


Comparative Study of the Efficacy of the Ovarian-Adnexa Reporting and Data System Ultrasound Combined With Contrast-Enhanced Ultrasound and the ADNEX MR Scoring System in the Diagnosis of Adnexal Masses.
The aims of this study were to develop the Ovarian-Adnexa Reporting and Data System (O-RADS) and O-RADS + contrast-enhanced ultrasound (O-RADS CEUS) scoring system to distinguish adnexal masses (AMs) and to compare the diagnostic efficacy of these systems with that of a magnetic resonance imaging scoring system (ADNEX MR). We retrospectively evaluated 278 ovarian masses from 240 patients between May 2017 and July 2022. Pathology and adequate follow-up were used as reference standards for comparing the validity of O-RADS, O-RADS CEUS and ADNEX MR scoring to diagnose AMs. Area under the curve (AUC), sensitivity and specificity were calculated. The inter-class correlation coefficient (ICC) was calculated to evaluate inter-reader agreement (IRA) between the two sonographers and two radiologists who analyzed the findings with the three modalities. The AUCs of O-RADS, O-RADS CEUS and ADNEX MR scores were 0.928 (95% confidence interval [CI]: 0.895-0.956), 0.951(95% CI: 0.919-0.973) and 0.964 (95% CI: 0.935-0.983), respectively. Their sensitivities were 95.7%, 94.3 and 91.4%, and their specificities were 81.3%, 92.3% and 97.1%, respectively. The three modalities had accuracies of 84.9%, 92.8% and 95.7%, respectively. O-RADS had the highest sensitivity but significantly lower specificity (p < 0.001), whereas the ADNEX MR scoring had the highest specificity (p < 0.001) but lower sensitivity (p < 0.001). O-RADS CEUS had intermediate sensitivity and specificity (p < 0.001). The addition of CEUS significantly improves the efficacy of O-RADS in diagnosing AMs. The diagnostic efficacy of the combination is comparable to that of the ADNEX MR scoring system.


Stereoselective Michael-aldol tandem reaction of phenylselenomagnesium bromide with acetylenic sulfones and aldehydes. An efficient synthesis of polyfunctionalized allylic alcohols.
A mixture of phenylselenomagnesium bromide, an acetylenic sulfone, and an aldehyde in THF/CH(2)Cl(2) afforded Michael-aldol tandem adduct, i.e., (Z)-beta-phenylseleno-alpha-(p-tolylsulfonyl)allylic alcohol, in good yield with high stereoselectivity. The stereoselectivity greatly depended on solvent. [reaction: see text]


Projections of the ascending somesthetic pathways to the cat superior colliculus visualized by the horseradish peroxidase technique.
Projections of the somesthetic ascending pathways to the superior colliculus (SC) of the cat have been demonstrated by means of the horseradish peroxidase (HRP) tracing technique. Following HRP injection in one SC, marked neurons were found in the contralateral dorsal horn and in the contralateral dorsal column nuclei, mainly the cuneate nucleus. Moreover, in the contralateral trigeminal complex, the sub-nucleus caudalis of the spinal nucleus of the Vth nerve, and the subnucleus oralis plus the main sensory trigeminal nucleus were labeled. Thus, the anterolateral system and the lemniscal system subserving face and forelimb sensation send afferent fibers to the contralateral SC.


Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms.
Behavioral disturbances occur frequently in demented individuals and greatly increase the burden of their care. The efficacy of pharmacotherapeutic treatment options is modest. This study was conducted to explore the efficacy and safety of dronabinol as an adjunctive treatment for agitation and aggressive behavior in severely demented patients. Using a retrospective systematic chart review, we studied 40 inpatients from the McLean Hospital Geriatric Neuropsychiatry Inpatient Unit diagnosed with dementia and treated with dronabinol for behavioral or appetite disturbances. A group of geriatric psychiatrists consulted medical records to rate the patients' behaviors prior to initiation of dronabinol treatment and following up to seven days of treatment, using the Pittsburgh Agitation Scale, Clinical Global Impression, and Global Assessment of Functioning. Data on percentage of food consumed at each meal, sleep duration, and adverse events were also collected from medical records. The addition of dronabinol to patients' treatment regimens was associated with significant decreases in all domains of the Pittsburgh Agitation Scale. There were also significant improvements in Clinical Global Impression scores, sleep duration and percentage of meals consumed during the treatment periods. Twenty-six adverse events were recorded during dronabinol treatment, none of which led to medication discontinuation. This report represents the largest studied cohort of dementia patients treated with dronabinol to date and confirms earlier reports that dronabinol can serve as an adjunctive treatment for neuropsychiatric symptoms in dementia. Further research, including prospective controlled trials, is needed to clarify dronabinol's role in treating noncognitive behavioral symptoms of demented individuals.


[Ten key messages of the guidelines for family-centered care in intensive care medicine].
The family plays an important role in the care of the critically ill patient. There is a substantial psychological burden to family members during the intensive care management of the patient. The family has to bear the pitiable state of the patient with the feeling of helplessness. The critically ill patient is frequently unable to actively decide on the processes of intensive care. Therefore, the family has to take over the responsibility of representing the values and wishes of the patient and become involved in decision making, for which most family members are not prepared. A considerable proportion of family members suffers from stress, anxiety and depression. This psychological burden also continues after the conclusion of the intensive care management. Therefore, structured approaches are needed to support family members of critically ill patients during the intensive care management. In this short review, we present the ten key messages of the recent guidelines for family-centered care in the intensive care unit by the Society of Critical Care Medicine.


Demystifying Monarch Butterfly Migration.
Every fall, millions of North American monarch butterflies undergo a stunning long-distance migration to reach their overwintering grounds in Mexico. Migration allows the butterflies to escape freezing temperatures and dying host plants, and reduces infections with a virulent parasite. We discuss the multigenerational migration journey and its evolutionary history, and highlight the navigational mechanisms of migratory monarchs. Monarchs use a bidirectional time-compensated sun compass for orientation, which is based on a time-compensating circadian clock that resides in the antennae, and which has a distinctive molecular mechanism. Migrants can also use a light-dependent inclination magnetic compass for orientation under overcast conditions. Additional environmental features, e.g., atmospheric conditions, geologic barriers, and social interactions, likely augment navigation. The publication of the monarch genome and the development of gene-editing strategies have enabled the dissection of the genetic and neurobiological basis of the migration. The monarch butterfly has emerged as an excellent system to study the ecological, neural, and genetic basis of long-distance animal migration.


Polysystic ovary syndrome--loss of the apoptotic mechanism in the ovarian follicles?
Polycystic ovary syndrome (PCOS) is the most prevalent female endocrinopathy and the largest single cause of anovulatory infertility. The PCOS is characterized by multiple small antral follicles arrested in their development but nonatretic and viable. The hyperexpression of some growth factors (e.g. EGF/TGF alpha) in PCOS, considered to be survival or antiapoptotic factors, led to the hypothesis of their involvement in the blocking of apoptosis and atresia leading to an accumulation of multiple small antral follicles. Diminished FSH stimulation and accumulation of androgens could explain the arrest of progress to the preovulatory stage. Further investigation of the pathogenesis of PCOS is needed on the modulation of tumour suppressor and apoptosis genes such as p53, BAX or the APO/FAS system and the over expression of survival genes such as BCL2.


Interaction of DPPC liposomes with cholesterol and food protein during in vitro digestion using Dynamic Light Scattering and FTIR spectroscopy analysis.
The influence of cholesterol (CHO), bovine serum albumin (BSA) and lactoferrin (LF), on the phase transition temperature (Tm) and structure of DPPC liposomes during in vitro digestion was investigated using Dynamic Laser Scattering (DLS) and Fourier Transform Infrared Spectroscopy technologies (FTIR). CHO enhanced bilayers thickness and acyl chain order, especially in DPPC:CHO of 6:1, with the average size increase to 1.77 ± 0.20 μm and broaden of phase transition (Tm 45.8 °C). Protein critically impacted on the liposomal structure through formation of hydrogen bonds between in DPPC and protein. Liposomal size and Tm were significantly changed after simulated gastric digestion, whereas the pancreatic incubation can broaden transition phase and weaken functional groups of liposomes. Our data provided a better understanding on structure changes of CHO-containing membrane and protein addition by revealing Tm and chemical bonds details, and added to current knowledge for evaluating the different component on liposomal digestibility in food area.


Epidemiology and biology of a herpesvirus in rabies endemic vampire bat populations.
Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Virally vectored vaccines that spread autonomously through bat populations are a theoretically appealing solution to managing rabies in its reservoir host. We investigate the biological and epidemiological suitability of a vampire bat betaherpesvirus (DrBHV) to act as a vaccine vector. In 25 sites across Peru with serological and/or molecular evidence of rabies circulation, DrBHV infects 80-100% of bats, suggesting potential for high population-level vaccine coverage. Phylogenetic analysis reveals host specificity within neotropical bats, limiting risks to non-target species. Finally, deep sequencing illustrates DrBHV super-infections in individual bats, implying that DrBHV-vectored vaccines might invade despite the highly prevalent wild-type virus. These results indicate DrBHV as a promising candidate vector for a transmissible rabies vaccine, and provide a framework to discover and evaluate candidate viral vectors for vaccines against bat-borne zoonoses.


Unique substrate recognition mechanism of the botulinum neurotoxin D light chain.
Botulinum neurotoxins are the most potent protein toxins in nature. Despite the potential to block neurotransmitter release at the neuromuscular junction and cause human botulism, they are widely used in protein therapies. Among the seven botulinum neurotoxin serotypes, mechanisms of substrate recognition and specificity are known to a certain extent in the A, B, E, and F light chains, but not in the D light chain (LC/D). In this study, we addressed the unique substrate recognition mechanism of LC/D and showed that this serotype underwent hydrophobic interactions with VAMP-2 at its V1 motif. The LC/D B3, B4, and B5 binding sites specifically recognize the hydrophobic residues in the V1 motif of VAMP-2. Interestingly, we identified a novel dual recognition mechanism employed by LC/D in recognition of VAMP-2 sites at both the active site and distal binding sites, in which one site of VAMP-2 was recognized by two independent, but functionally similar LC/D sites that were complementary to each other. The dual recognition strategy increases the tolerance of LC/D to mutations and renders it a good candidate for engineering to improve its therapeutic properties. In conclusion, in this study, we identified a unique multistep substrate recognition mechanism by LC/D and provide insights for LC/D engineering and antitoxin development.


Partial characterization of a transformation-specific glycopeptide in SSV-NP cells.
An autologous antiserum against simian sarcoma virus-infected nonproducer cells (SSV-NP cells) recognized a SSV transformation-specific glycopeptide (SSV-TrSgp) [H.-J. Thiel, T.J. Matthews, E.M. Broughton, A.M. Butchko, and D.P. Bolognesi (1981) Virology 112, 642-650]. Gel filtration of this component on a Sephacryl S-200 column indicated an apparent molecular weight at about 200,000 (d). This antigen represented a proteoglycan-like molecule, as evidenced by the size of glycopeptides after Pronase treatment and by incubation with chondroitinases. The antigenicity of the SSV-TrSgp was completely destroyed after exposure to different proteases. On the other hand, incubation with neuraminidase or chondroitinases degraded the molecule to some extent, but did not affect its antigenicity as measured by immunoprecipitation. Trypsin and EDTA treatment of intact pulse-labeled cells, as well as surface iodination, indicated that the SSV-TrSgp represents a cell membrane-associated molecule.


Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation.
Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation. Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli beta-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants. The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [(3)H]thymidine and [(35)S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis. These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal.


Association of Sodium-Glucose Cotransporter-2 Inhibitors With Fracture Risk in Older Adults With Type 2 Diabetes.
Whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are associated with an increased risk of fractures in older adults with type 2 diabetes (T2D) outside of clinical trials remains unknown. To examine the association of incident fracture among older adults with T2D with initiating an SGLT-2i compared with initiating a dipeptidyl peptidase 4 inhibitor (DPP-4i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA). This is a population-based, new-user cohort study including older adults (aged ≥65 years) with T2D enrolled in Medicare fee-for-service from April 2013 to December 2017. Data analysis was performed from October 2020 to April 2021. New users of an SGLT-2i, DPP-4i, or GLP-1RA without a previous fracture were matched in a 1:1:1 ratio using 3-way propensity score matching. The primary outcome was a composite end point of nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention within 30 days. After 3-way 1:1:1 propensity score matching, multivariable Cox proportional hazards regression models were used to generate hazard ratios (HRs) for SGLT-2i compared with DPP-4i and GLP-1RA and Kaplan-Meier curves to visualize fracture risk over time across groups. Of 466 933 new initiators of study drugs, 62 454 patients were new SGLT-2i users. After 3-way matching, 45 889 (73%) new SGLT-2i users were matched to new users of DPP-4i and GLP-1RA, yielding a cohort of 137 667 patients (mean [SD] age, 72 [5] years; 64 126 men [47%]) matched 1:1:1 for analyses. There was no difference in the risk of fracture in SGLT-2i users compared with DPP-4i users (HR, 0.90; 95% CI, 0.73-1.11) or GLP-1RA users (HR, 1.00; 95% CI, 0.80-1.25). Results were consistent across categories of sex, frailty (nonfrail, prefrail, and frail), age (<75 and ≥75 years), and insulin use (baseline users and nonusers). In this nationwide Medicare cohort, initiating an SGLT-2i was not associated with an increased risk of fracture in older adults with T2D compared with initiating a DPP-4i or GLP-1RA, with consistent results across categories of frailty, age, and insulin use. These findings add to the evidence base evaluating the potential risks associated with SGLT-2i use for older adults outside of randomized clinical trials.


Changes in dimensions of large cancellous bone specimens during histological preparation as measured on slabs from human femoral heads.
Distortion of the dimensions of large cancellous bone specimens during all stages of histological processing and cutting of paraffin sections in various directions was measured on Xerograms taken from slabs and then sections from human femoral heads. Although some shrinkage in both width and height of the specimens occurred at every stage of the histological preparation, the main shrinkage (about 6%) occurred during the embedding process, and mainly in the cutting of the sections (10-27%, depending on the direction the knife was approaching the specimen). The shrinkage of cancellous bone tissue during histological preparation appears to be a constant factor, but its magnitude during the individual stages of the preparation can be predicted. For the quantitative measurements a comparison of two Xerograms--one taken from the original fresh bone slab and the other from the final stained section--would reveal the exact extent of the tissue shrinkage.


A review of the subfamily Acaenitinae Förster, 1869 (Hymenoptera, Ichneumonidae) from Ukrainian Carpathians.
Ichneumonid wasps of the subfamily Acaenitinae Förster, 1869 are reviewed for the first time from the Ukrainian Carpathians. Two species, Coleocentrusexareolatus Kriechbaumer, 1894 and Coleocentrusheteropus Thomson, 1894 are new records for Ukraine. Arotesannulicornis Kriechbaumer, 1894 is considered to be a junior synonym of Arotesalbicinctus Gravenhorst, 1829 (syn. nov.). A key to species of Coleocentrus of the Carpathians is provided.


Levels of a subpopulation of platelets, but not circulating endothelial cells, predict early treatment failure in prostate cancer patients after prostatectomy.
Angiogenesis is one of the hallmarks of cancer driving tumour growth and ultimately metastasis. Circulating endothelial cells (CECs) and circulating endothelial progenitor (CEPs) cells have been reported as candidate surrogate markers for tumour vascularisation. Our aim was to investigate the potential use of these circulating cells levels as predictors of prostate cancer treatment failure and metastasis. We examined the levels of CD31(+)CD45(-) cells (CECs) and CD31(+)CD45(-)CD117(+) (CEPs) in s.c. and orthotopic models of human prostate cancers and correlated measurements with tumour size, volume and microvessel density (MVD). We then performed a prospective cohort study in 164 men with localised prostate cancer undergoing prostatectomy. The CD31(+)CD45(-), CD31(+)CD45(-)CD146(+) (CECs) and CD31(+)CD45(intermediate)CD133(+) (CEPs) populations were quantified and subsequently enriched for further characterisation. In preclinical models, levels of CD31(+)CD45(-) cells, but not CEPs, were significantly elevated in tumour-bearing mice and correlated with tumour size, volume and MVD. In our human prospective cohort study, the levels of CD31(+)CD45(-) cells were significantly higher in men who experienced treatment failure within the first year, and on logistic regression analysis were an independent predictor of treatment failure, whereas neither levels of CECs or CEPs had any prognostic utility. Characterisation of the isolated CD31(+)CD45(-) cell population revealed an essentially homogenous population of large, immature platelets representing <0.1% of circulating platelets. Elevated levels of a distinct subpopulation of circulating platelets were an independent predictor for early biochemical recurrence in prostate cancer patients within the first year from prostatectomy.


Transvaginal myomectomy with screw traction by colpotomy.
The aim of this study is to evaluate the clinical effectiveness and safety of the enucleation of uterine leiomyomas by traction method via colpotomy. Ten women with menorrhagia, pelvic pain, or secondary infertility associated with single uterine myomas underwent transvaginal myomectomy with screw traction by colpotomy. The feasibility of the procedure, operative complications, postoperative recovery, pregnancies, and relief of symptoms were the main outcome measures. Traction myomectomy was completed vaginally in all patients. The mean operating time was 71 min and average blood loss 385 ml. The mean size of a single myoma was 6.7 cm (range 5.6-8.0 cm) and weight 153 g. One patient developed a transient hematoma. All women reported relief of their symptoms after a mean follow-up of 24 months. Three patients had a term delivery postoperatively. Traction myomectomy by colpotomy is a feasible approach for selected patients wishing to preserve their ability to conceive. A single well-lined myoma of 5-8 cm diameter and possible to reach via colpotomy is a suitable subject for the procedure, which proved a viable surgical approach.


Luxury perfusion syndrome confirmed by sequential studies of regional cerebral blood flow and volume after extracranial to intracranial bypass surgery: case report.
We report a case of luxury perfusion syndrome with temporary neurological deterioration after extracranial to intracranial bypass surgery. A preoperative computed tomographic scan showed no detectable infarct, and the measurement of regional cerebral blood flow showed severe depression of ipsilateral hemispheric perfusion. The patient developed temporary neurological deterioration after bypass surgery, with no recognizable pathological signs on postoperative computed tomographic and angiographic studies. Regional cerebral blood flow and volume were more elevated during the period of neurological deterioration than after the subsequent recovery. This strongly suggests that excessive blood flow directed into chronically ischemic brain through a graft may induce a luxury perfusion syndrome resulting in neurological deterioration.


The Whole Body as the System in Systems Immunology.
The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue homeostasis. Although much of our understanding of human immunology has derived from studies of peripheral blood, recent work utilizing human tissue resources and innovative computational methods have employed a whole-body, systems-based approach, revealing tremendous complexity and heterogeneity of the immune system within individuals and across the population. In this review, we discuss how tissue localization, developmental and age-associated changes, and conditions of health and disease shape the immune response, as well as how improved understanding of interindividual and tissue-specific immunity can be leveraged for developing targeted therapeutics.


Data to understand the biotransfer of heavy metals along the soil-plant-edible insect-human food chain in Africa.
Data on the biotransfer of heavy metals along the soil-plant-edible insect-human food chain collected along a 60km pollution gradient is presented here. These datasets consists of concentrations of eight heavy metals (Arsenic, Cadmium, Copper, Chromium, Iron, Nickel, Lead and Zinc) in the soils, in five host plants species, and in seven edible insect species determined using Atomic Absorption Spectrophotometry (AAS). Datasets for the daily intake of metals and target hazard quotients for each edible insect species are also given. These data demonstrate the potential biotransfer of heavy metals along the soil-plant-edible insect-human food chain, and that edible insects harvested in heavy metal-polluted environments could pose serious health risks. These datasets provide further understanding of the relationships among metal concentrations in the soils, host plants and edible insects, particularly in the mining regions. For further details, refer to the article, "Biotransfer of heavy metals along the soil-plant-edible insect-human food chain in Africa" Mwelwa et al., [1].