Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae.
Streptococcus mitis is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, in silico analyses indicated the presence of an Rgg regulator and short hydrophobic peptide (Rgg/SHP) cell-to-cell communication system in S. mitis Although Rgg presented greater similarity to a repressor in Streptococcus pyogenes, autoinducing assays and genetic mutation analysis revealed that in S. mitis Rgg acts as an activator. Transcriptome analysis showed that in addition to shp, the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in Streptococcus pneumoniae indicated that S. mitis lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of autoinduction, growth was not significantly affected for the rgg mutant under normal or antibiotic stress conditions. The S. mitis SHP was, however, fully functional in promoting cross-species communication and increasing S. pneumoniae surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in cocultures using a S. mitis reporter strain. In competitive assays, a slight advantage was observed for the rgg mutants. We conclude that the Rgg/SHP system in S. mitis regulates the expression of its own shp and activates an Rgg/SHP system in S. pneumoniae that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multispecies interactions.IMPORTANCE Bacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in Streptococcus mitis, a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with S. pneumoniae, a closely related major human pathogen. Importantly, we show that this cross-communication can take place during coculture. While the genes regulated in S. mitis are likely part of a futile cycle of activation, the target genes in S. pneumoniae are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.


Major disagreements between immunoassays of carcinoembryonic antigen may be caused by nonspecific cross-reacting antigen 2 (NCA-2).
Four "sandwich"-type immunoassays of carcinoembryonic antigen (CEA) based on the use of monoclonal antibodies (Abbott CEA-RIA Monoclonal, Pharmacia/Wallac Delfia CEA kit, Roche CEA EIA Duomab 60, and our in-house immunoradiometric assay) were tested for cross-reaction with nonspecific cross-reacting antigen 2 (NCA-2) in meconium. The Roche assay did not react with NCA-2, but the other three assays cross-reacted strongly and to about the same extent with this antigen. NCA-2 is the CEA gene family member that is structurally most similar to CEA, and other authors have found by indirect evidence that this antigen also is increased in the serum of many cancer patients. In a previous study we found that the Roche assay yielded lower mean values than the other assays for CEA in serum from colorectal cancer patients. Furthermore, the correlation between the Roche CEA values and those of each of the other three assays was weaker than the correlation between these NCA-2 cross-reactive assays. We conclude that these results can be explained by the different cross-reactivity with NCA-2 of the antibodies used by the various assays, as described here. Our findings raise interesting questions regarding the possible role of NCA-2 as a tumor marker.


An RCM strategy to stereodiverse delta-sultam scaffolds.
An asymmetric approach for the synthesis of substituted delta-sultams with multiple synthetic handles is described. This study demonstrates the facile construction of a stereochemically diverse array of substituted delta-sultams, more specifically substituted 3,4,5,6-dihydro 1,2-thiazine 1,1-dioxides. A pivotal Mitsunobu alkylation/RCM sequence is used to assemble key allyl sultam building blocks possessing a C3 stereogenic handle. All subsequent reactions are achieved with high levels of diastereoselectivity to afford enantiopure delta-sultams in good yields.


Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma.
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Limited treatment options have only marginally impacted patient survival over the past decades. The phophatidylinositol 3-kinase (PI3K) pathway, frequently altered in GBM, represents a potential target for the treatment of this glioma. 5-(6,6-Dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine (GDC-0084) is a PI3K inhibitor that was specifically optimized to cross the blood-brain barrier. The goals of our studies were to characterize the brain distribution, pharmacodynamic (PD) effect, and efficacy of GDC-0084 in orthotopic xenograft models of GBM. GDC-0084 was tested in vitro to assess its sensitivity to the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) and in vivo in mice to evaluate its effects on the PI3K pathway in intact brain. Mice bearing U87 or GS2 intracranial tumors were treated with GDC-0084 to assess its brain distribution by matrix-assisted laser desorption ionization (MALDI) imaging and measure its PD effects and efficacy in GBM orthotopic models. Studies in transfected cells indicated that GDC-0084 was not a substrate of P-gp or BCRP. GDC-0084 markedly inhibited the PI3K pathway in mouse brain, causing up to 90% suppression of the pAkt signal. MALDI imaging showed GDC-0084 distributed evenly in brain and intracranial U87 and GS2 tumors. GDC-0084 achieved significant tumor growth inhibition of 70% and 40% against the U87 and GS2 orthotopic models, respectively. GDC-0084 distribution throughout the brain and intracranial tumors led to potent inhibition of the PI3K pathway. Its efficacy in orthotopic models of GBM suggests that it could be effective in the treatment of GBM. GDC-0084 is currently in phase I clinical trials.


An online educational model in andrology for student training in the art of scientific writing in the COVID-19 pandemic.
In 2020, the COVID-19 pandemic led to the suspension of the annual Summer Internship at the American Center for Reproductive Medicine (ACRM). To transit it into an online format, an inaugural 6-week 2020 ACRM Online Mentorship Program was developed focusing on five core pillars of andrology research: scientific writing, scientific methodology, plagiarism understanding, soft skills development and mentee basic andrology knowledge. This study aims to determine mentee developmental outcomes based on student surveys and discuss these within the context of the relevant teaching and learning methodology. The mentorship was structured around scientific writing projects established by the team using a student-centred approach, with one-on-one expert mentorship through weekly formative assessments. Furthermore, weekly online meetings were conducted, including expert lectures, formative assessments and social engagement. Data were collected through final assessments and mentee surveys on mentorship outcomes. Results show that mentees (n = 28) reported a significant (p < .0001) improvement in all criteria related to the five core pillars. These results illustrate that the aims of the online mentorship program were achieved through a unique and adaptive online educational model and that our model has demonstrated its effectiveness as an innovative structured educational experience through the COVID-19 crisis.


Mechanical properties of tantalum carbide from high-pressure/high-temperature synthesis and first-principles calculations.
As a member of the refractory metal carbide family of materials, TaC is a promising candidate for ultra-high temperature ceramics (UHTC) with desirable mechanical strength. TaC sample quality and therefore mechanical properties are strongly dependent on synthesis method, and atomistic origins of mechanical failure are difficult to assign. Here, we have successfully synthesized high quality densified TaC samples at 5.5 GPa and 1400 °C using the high pressure and high temperature (HPHT) sintering method, with Vickers hardness determined to be 20.9 GPa. First-principles calculations based on the recently developed strain-stress method show that the ideal indentation strength of TaC is about 23.3 GPa in the (11[combining macron]0)[001] direction, in excellent agreement with experimental results. The detailed indentation shear deformation analysis and structural snapshots from the calculations indicate that the slip dislocations of TaC layers are the main structural deformation mode during the Vickers indentation process, and that the strong directional Ta-C bonds are responsible for the high mechanical strength of TaC. HPHT synthesis is shown to produce TaC samples with superior strength, and together with accurate first-principles calculations offers crucial insights for rational design and synthesis of novel and advanced UHTC materials.


Reovirus-based therapy for cancer.
Reovirus is an oncolytic virus that is not associated with significant disease in humans, but is selectively able to replicate in cancer cells through exploitation of abnormal Ras signaling. Pre-clinical studies have demonstrated that treatment with reovirus is associated with significant anticancer activity across a range of tumor types. Reolysin is a proprietary formulation of the human reovirus developed by Oncolytics Biotech. Clinical evaluation of reovirus therapy has shown that it is well tolerated when administered locally or systemically. Encouraging anticancer efficacy has been observed with single-agent treatment and in combination with chemotherapy and radiotherapy. Phase II studies are currently evaluating reovirus alone and in combination with standard therapy in an array of tumor types. While immune sensitization hinders the anticancer efficacy of reovirus, it is important in preventing systemic toxicity. Immunosuppressive strategies are being developed that reduce immune neutralization of the virus to allow for improved tumor penetration, but retain sufficient antibody levels to protect normal tissues. The lack of toxicity and promising efficacy of reovirus has raised hopes that it will become an established anticancer agent.


Tbx2 controls lung growth by direct repression of the cell cycle inhibitor genes Cdkn1a and Cdkn1b.
Vertebrate organ development relies on the precise spatiotemporal orchestration of proliferation rates and differentiation patterns in adjacent tissue compartments. The underlying integration of patterning and cell cycle control during organogenesis is insufficiently understood. Here, we have investigated the function of the patterning T-box transcription factor gene Tbx2 in lung development. We show that lungs of Tbx2-deficient mice are markedly hypoplastic and exhibit reduced branching morphogenesis. Mesenchymal proliferation was severely decreased, while mesenchymal differentiation into fibrocytes was prematurely induced. In the epithelial compartment, proliferation was reduced and differentiation of alveolar epithelial cells type 1 was compromised. Prior to the observed cellular changes, canonical Wnt signaling was downregulated, and Cdkn1a (p21) and Cdkn1b (p27) (two members of the Cip/Kip family of cell cycle inhibitors) were strongly induced in the Tbx2-deficient lung mesenchyme. Deletion of both Cdkn1a and Cdkn1b rescued, to a large degree, the growth deficits of Tbx2-deficient lungs. Prolongation of Tbx2 expression into adulthood led to hyperproliferation and maintenance of mesenchymal progenitor cells, with branching morphogenesis remaining unaffected. Expression of Cdkn1a and Cdkn1b was ablated from the lung mesenchyme in this gain-of-function setting. We further show by ChIP experiments that Tbx2 directly binds to Cdkn1a and Cdkn1b loci in vivo, defining these two genes as direct targets of Tbx2 repressive activity in the lung mesenchyme. We conclude that Tbx2-mediated regulation of Cdkn1a and Cdkn1b represents a crucial node in the network integrating patterning information and cell cycle regulation that underlies growth, differentiation, and branching morphogenesis of this organ.


Regional ventilation changes in severe asthma after bronchial thermoplasty with (3)He MR imaging and CT.
To quantify regional lung ventilation in healthy volunteers and patients with severe asthma (both before and after thermoplasty) by using a combination of helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT), with the intention of developing more effective image-guided treatments for obstructive lung diseases. With approval of the local institutional review board, informed consent, and an Investigational New Drug Exemption, six healthy volunteers and 10 patients with severe asthma were imaged in compliance with HIPAA regulations by using both multidetector CT and (3)He MR imaging. Individual bronchopulmonary segments were labeled voxel by voxel from the CT images and then registered to the (3)He MR images by using custom software. The (3)He signal intensity was then analyzed by evaluating the volume-weighted fraction of total-lung signal intensity present in each segment (segmental ventilation percentage [ SVP segmental ventilation percentage ]) and by identifying the whole-lung defect percentage and the segmental defect percentage. Of the 10 patients with asthma, seven received treatment with bronchial thermoplasty and were imaged with (3)He MR a second time. Changes in segmental defect percentages and whole-lung defect percentages are presented. Ventilation measures for healthy volunteers yielded smaller segment-to-segment variation (mean SVP segmental ventilation percentage , 100% ± 18 [standard deviation]) than did the measures for patients with severe asthma (mean SVP segmental ventilation percentage , 97% ± 23). Patients with asthma also demonstrated larger segmental defect percentages (median, 13.5%; interquartile range, 8.9%-17.8%) than healthy volunteers (median, 6%; interquartile range, 5.6%-6.3%). These quantitative results confirm what is visually observed on the (3)He images. A Spearman correlation of r = -0.82 was found between the change in whole-lung defect percentage and the number of days between final treatment and second (3)He imaging. Regional quantification of lung ventilation is indeed feasible and may be a useful technique for image-guided treatment of obstructive lung diseases, such as bronchial thermoplasty for severe asthma. In these patients, ventilation defects decreased as a function of time after treatment.


Comparison of various menopausal symptoms and risk factor analysis in Korean women according to stage of menopause.
To determine the prevalence and severity of menopausal symptoms and their related risk factors among middle-aged Korean women according to their reproductive stages. This cross-sectional study included 3039 Korean women, aged 45-65 years, who attended their routine health checkup. Their scores from the Menopause Rating Scale (MRS) were compared and participants were categorized into four groups according to stage of menopause: premenopause, early menopause (≤2 years from their last menstruation), mid-menopause (2-8 years), and late menopause (>8 years). The mean age of the participants was 52.81 ± 5.39 years, and 98.5 % of them reported one or more symptoms included in the MRS. The most common symptom was physical/mental exhaustion, experienced by 86.7 % of participants. The prevalence of moderate to severe symptoms, including vasomotor symptoms, heart discomfort, sleep problems, sexual problems, vaginal dryness, and joint/muscular discomfort, increased in the early menopausal period. This increased in the late menopausal period compared with its prevalence at premenopause. The prevalence of moderate to severe psychological symptoms, heart discomfort, and sleep problems followed a U-shaped trend after menopause: high at early menopause, low at mid-menopause, and high again at late menopause. A low level of physical exercise was an independent risk factor for a high total MRS score; however, the menopausal stages, age, and weight were also variously associated with menopausal symptoms. Several menopausal symptoms remain severe, or are aggravated, until the late menopausal period among Korean women. More attention is warranted to manage these symptoms in postmenopausal women.


[Energy metabolism in the cerebral cortex in necrosis of the myocardium].
In ischemic necrosis of myocardium inhibition of energy metabolism occurred in brain, as a result of which an impairment of the brain functional state might take place. Emotional stress, preceding the myocardium necrosis, augmented the impairments of energy metabolism in brain hemispheres.


Ichthyosiform scaling secondary to megavoltage radiotherapy.
Acquired ichthyosis is a rare dermatosis associated with a number of malignancies. Side effects seen on the skin secondary to megavoltage radiotherapy are uncommon but may include fine dry desquamation and tanning. We present a case of ichthyosiform scaling limited to the radiation fields in a patient treated for brain metastases of a primary small cell lung carcinoma. The reader is reminded that side effects of megavoltage treatment do occur on the skin. A brief review of these effects is included.


Early assessment of lateralization and sex influences on the microstructure of the white matter corticospinal tract in healthy term neonates.
We assessed the sex and the lateralization differences in the corticospinal tract (CST) during the early postnatal period. Twenty-five healthy term neonates (13 girls, aged 39.2 ± 1.2 weeks, and 12 boys aged 38.6 ± 3.0 weeks) underwent Diffusion Tensor Imaging (DTI). Fiber tracking was performed to extract bilaterally the CST pathways and to quantify the parallel (E1 ) and perpendicular (E23 ) diffusions, the apparent diffusion coefficient (ADC), and fractional anisotropy (FA). The measurements were performed on the entire CST fibers and on four segments: base of the pons (CST-Po), cerebral peduncles (CST-CP), posterior limb of the internal capsule (CST-PLIC), and corona-radiata (CST-CR). Significantly higher E1 , lower E23, and higher FA in the right compared to the left were noted in the CST-PLIC of the girls. Significantly lower E23 and lower ADC with higher FA in the right compared to left were observed in the CST-CP of the boys. Moreover, the CST-PLIC of the boys had significantly higher E1 in the right compared to the left. There was a significant increase in left CST E1 of boys when compared with girls. Girls had a significantly lower E1 , lower E23 and, lower ADC in the left CST-CP compared with boys. In addition, girls had a significantly lower E23 and higher FA in the right CST-PLIC compared with boys. Sex differences and lateralization in structure-based segments of the CST were found in healthy term infants during early postnatal period. These findings are vital to understanding motor development of healthy term born neonates to better interpret newborn infants with abnormal neurodevelopment.


Nickel-catalyzed Suzuki-Miyaura cross-couplings of aldehydes.
Transition-metal-catalyzed cross-couplings have been extensively used in the pharmaceutical and agrochemical industries for the construction of diverse C-C bonds. Conventional cross-coupling reactions require reactive electrophilic coupling partners, such as organohalides or sulfonates, which are not environmentally friendly and not naturally abundant. Another disadvantage associated with these transformations is the need for an exogenous base to facilitate the key transmetalation step, and this reagent inevitably induces side reactions and limits the substrate scope. Here, we report an unconventional Suzuki-type approach to the synthesis of biaryls, through nickel-catalyzed deformylative cross coupling of aldehydes with organoboron reagents under base-free conditions. The transformation tolerates structurally diverse (hetero)aryl substituents on both coupling partners and shows high reactivity and excellent functional group tolerance. Furthermore, the protocol was carried out on gram scale and successfully applied to the functionalization of complex biologically active molecules. Mechanistic investigations support a catalytic cycle involving the oxidative addition of the nickel into the aldehyde C(acyl)-H bond with subsequent hydride transfer, transmetalation, decarbonylation and reductive elimination processes.


CK19 mRNA expression in the bone marrow of patients with esophageal squamous cell carcinoma and its clinical significance.
The 5-year survival rate in resectable patients with esophageal cancer is only 20% to 36%. Regional relapse and distant metastasis are responsible for the failure of treatment and the majority of cancer-related deaths. Earlier detection of metastases, especially micrometastases, has the potential for more accurate risk stratification in subsequent therapy decisions. No effective techniques have yet been found to detect metastases in erroneously thought to have early stage disease. This study was designed to investigate the clinical significance of bone marrow micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with esophageal cancer. Expression of CK19 mRNA in the bone marrow of 61 patients with esophageal squamous cell carcinoma (ESCC) and 15 benign pulmonary and esophageal disease patients was assessed via RT-PCR. Correlation of CK19 mRNA expression to the clinicopathologic features and prognosis of the 61 patients was analyzed: 21.3% (13/61) were positive for expression of CK19 mRNA in patients with ESCC. No CK19 mRNA was detected of the 15 benign pulmonary and esophageal disease patients. CK19 mRNA expression did not correlate with the clinicopathologic features of the patients with ESCC, but patients with CK19 mRNA-positive bone marrow had earlier recurrence and shorter survival after surgery. In multivariate analysis, CK19 mRNA was found to be an independent predictor of a poor outcome. CK19 mRNA may be used as a molecular maker to detect bone marrow micrometastases in patients with ESCC and may help to select the proper therapy and predict the prognosis.


Tissue oxygen during a critical developmental period controls the death and survival of photoreceptors.
To study the death of photoreceptors in normally developing and dystrophic retina and to test the role of hypoxia in causing that death. Death of photoreceptors was detected in the albino, hooded, and Royal College of Surgeons (RCS) strains of rat, and in the rabbit and cat, using the TUNEL technique. Retinas of selected ages from animals raised normally and those from rat pups raised for periods in hyperoxia (75% oxygen) or hypoxia (10% oxygen) were studied. In all species and strains examined, a naturally occurring wave of photoreceptor death was detected during the last stages of retinal development. In the albino rat, this wave, which began approximately at postnatal day 15 (P15) and peaked at P22, was reduced by hyperoxia and was intensified by hypoxia, producing a "hypoxic dystrophy" of photoreceptors. In the RCS rat, photoreceptor death also commenced at approximately P15 and then proceeded to exhaustion. This degeneration was greatly reduced by hyperoxia. In the RCS rat, hyperoxia was effective in photoreceptor rescue only during a discrete period, from P16 to P22. In the albino rat, the effectiveness of hypoxia in inducing photoreceptor death was much greater between P15 and P21 than at earlier ages, or in the adult. During a critical period extending approximately from P15 to P22, tissue oxygen levels strongly influence photoreceptor death and survival in dystrophic and normally developing strains of rat. This period is evident in normal development as a period of naturally occurring photoreceptor death and is evident experimentally as a period during which hyperoxia is effective in rescuing dying photoreceptors and during which hypoxia is effective in inducing death of otherwise viable photoreceptors.


Mouse hematopoietic stem cells, unlike human and mouse embryonic stem cells, exhibit checkpoint-apoptosis coupling.
Previously, we reported that the spindle assembly checkpoint (SAC), which is coupled in somatic cells, is uncoupled from apoptosis-initiation in mouse and human embryonic stem cells (ESCs). This condition allows ESCs to tolerate and proliferate as polyploidy/aneuploid cells. Proper function of the SAC is vital to prevent polyploidy/aneuploidy during ex vivo hematopoietic stem cell (HSC) expansion. Here we address, for the first time, whether HSCs are more like ESCs or somatic cells with respect to SAC-apoptosis coupling. Using multiparametric permeablized cell flow-cytometric analysis to identify and analyze the mouse sca 1(+)/c-kit(+)/lin(-) (LSK) population, we found the mitotic spindle checkpoint to be functional in primary murine LSK cells, a population enriched in primitive hematopoietic stem/progenitor cells, after prolonged activation of the SAC by microtubule-depolymerizing agents such as nocodazole. HSCs can efficiently initiate apoptosis after activation of the SAC in LSK cells as indicated by increased hypodiploidy and increased levels of activated caspase 3, suggesting that HSCs behave more like somatic cells instead of ESCs with respect to this important cell cycle checkpoint. We conclude that mouse HSCs are not subject to the same kinds of chromosomal instability as are ESCs, knowledge that might aid in optimizing in vitro culture and expansion of human bone marrow or cord blood HSC for clinical applications.


Long-term use of antibiotics and risk of colorectal adenoma.
Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated. We prospectively evaluated the association between antibiotic use at age 20-39 and 40-59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16 642 women aged ≥60 enrolled in the Nurses' Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate ORs and 95% CIs. We documented 1195 cases of adenoma. Increasing duration of antibiotic use at age 20-39 (ptrend=0.002) and 40-59 (ptrend=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared with non-users, women who used antibiotics for ≥2 months between age 20 and 39 had a multivariable OR of 1.36 (95% CI 1.03 to 1.79). Women who used ≥2 months of antibiotics between age 40 and 59 had a multivariable OR of 1.69 (95% CI 1.24 to 2.31). The associations were similar for low-risk versus high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past four years was not associated with risk of adenoma (ptrend=0.44). Long-term antibiotic use in early-to-middle adulthood was associated with increased risk of colorectal adenoma.


[Epidemiological health surveillance among the troops during combat operations in armed conflicts].
With local wars and armed conflicts the sanitary-epidemiological situation for the troops and local population shows a tendency to worsen. The main objects of the military medical service at the period of deployment are the preventive measures against troops infection from local sources by virus hepatitis A, bacterial dysentery, typhoid, cholera etc. As a rule, combat actions result in communal service destruction, low quality of potable water, soil contamination and worsening sanitary norms and standards. Also, there is a danger of reactivation of the natural centres of infection due to large-scale defence earthworks in the region of operations. The experience of the military medical service in Afghanistan and Chechnya proves, that a multimedia approach to preventive antiepidemic measures is necessary together with the emphasis on the most important actions against infections that represent the biggest danger for the land troops.


A low-complexity PPG pulse detection method for accurate estimation of the pulse rate variability (PRV) during sudden decreases in the signal amplitude.
One of the biggest obstacles to reliable pulse rate variability (PRV) analysis is the erroneous detection of photoplethysmographic (PPG) pulses. Among all the disturbances that may hinder pulse detection, the ripples appearing at the smooth segments of the PPG signal can become a serious problem when the amplitude of the signal decreases considerably. To present a low-complexity PPG pulse detection method for reliable PRV estimation under conditions in which a sudden decrease in the amplitude of the PPG signal can be expected. 2-min ECG and PPG data (sampling rate at 500 Hz) were obtained from thirty healthy subjects, who were asked to take a deep inspiration to provoke a sudden amplitude decrease (SAD) of the PPG signal. After introducing a new parameter denoted as C, through which it is possible to jump over the ripples hindering the accurate detection of the systolic peaks, 500 Hz-sampled PPG recordings were down-sampled (400, 300, 200 and 100 Hz) to investigate the effect of the sampling rate on pulse detection. For ECG recordings, automatic R-peak detection was performed by the Pan and Tompkins (PT) algorithm, whereas PPG pulse detection was performed by the well-known maximum of the first derivative (M1D) and the proposed method, once the C-value for best detection results on 500 Hz-sampled PPG recordings was found. The agreement between heart rate variability (HRV) and PRVs estimated from each pulse detection method was assessed and the correlation between HRV and PRV-derived indexes was computed for comparison. The proposed method can perform well on PPG-SAD segments, provided that the proper value of the parameter C is used. Moreover, a good agreement between HRV and PRV series, as well as lower relative errors and higher correlation coefficients between HRV and PRV indexes, were achieved by the proposed pulse detection method during SADs. Results show that the proposed method can dynamically adapt to circumstances in which a decrease in the amplitude of the PPG signal can be expected, providing continuous systolic peak detection and reliable PRV estimation under those conditions. However, more extensive testing under a wide range of conditions is needed to perform a more rigorous validation.


Real-time PCR using high-resolution melting analysis technology for diagnosis of Leishmania and determination of types of clinical samples
Leishmaniasis is a disease group carried by Phlebotomus and Lutzomyia sand flies infected with Leishmania and is mostly observed in rural areas. In this study, using high-resolution melting analysis (HRMA), we aim to identify the active types of leishmaniasis, which are inadequately identified by classical methods. Samples of 85 patients were examined in the study. Six of the patients were suspected of having visceral leishmaniasis (VL) and 79 cutaneous leishmaniasis (CL). The slides prepared from the samples were stained with Giemsa stain and examined under a light microscope. The results were compared with those determined in real-time PCR. When the real-time PCR result was positive for Leishmania , we determined the type by HRMA. Among 85 Leishmania amastigote samples, 28 (32.9%) of them were detected and accepted as positive by microscopic examination. On the other hand, 25 (29.4%) of the 85 samples were found as positive using real-time PCR. In addition, when 25 Leishmania-positive samples were examined by HRMA, the results showed that 21 (84%) were L. tropica, 3 (12%) were L. major, and 1 (4%) was L. infantum. Based on our findings, we conclude that using real-time PCR and HRMA is useful in determining the cause of the disease in leishmaniasis.


Assessment of cardiovascular alterations and catecholamines serum concentration after oral surgery in patients receiving local anesthetics with epinephrine: a randomized, blind, controlled clinical trial.
A randomized controlled clinical trial was developed to evaluate the cardiovascular effects of local anesthetics with vasoconstrictors (LAVC) in healthy and hypertensive patients undergoing teeth extraction with lidocaine 2% with epinephrine 1:100,000. Twenty patients were divided into control (CG - normotensive patients) and experimental groups (EG - hypertensive patients). The variables analyzed were heart rate (HR), oxygen saturation (SO2), systolic and diastolic blood pressure (SBP and DBP), serum catecholamine concentration (dopamine, epinephrine, and norepinephrine), ventricular and supraventricular extrasystoles (VES and SVES respectively), and ST segment depression. Data was obtained in three different moments (initial, trans, and final). Blood samples were taken to measure the catecholamines, and a Holter device was used to measure data from the electrocardiogram including a 24-h postoperative evaluation period. The Mann-Whitney test was used to identify differences between the two groups, and the Friedman test with the adjusted Wilcoxon posttest was used for intragroup evaluation for repeated measures. The EG presented a lower O2S in the initial period (p = 0,001) while the sysBP showed a statistical difference for the three evaluation periods with the EG presenting the highest values. The VES was higher for the EG during the 24-h postoperative evaluation period (p = 0,041). The SVES and the serum catecholamines showed were similar between the groups. The intragroup analysis revealed significant statistical difference for the sysBP in the EG with the trans period presenting the highest measurements. The extrasystole evaluation showed that the 24-h postoperative period presented most events with only the CG not presenting statistical difference for the variable VES during this period (p = 0,112). No ST segment depression was noticed for both groups. Teeth extraction with LAVC can be safely executed in hypertensive patients. Blood pressure should be monitored in these patients since the sysBP presented significant differences during the surgical procedures. Cardiac arrhythmia and the serum catecholamines concentration levels seem not to be altered by the surgical procedure. Also, serum catecholamines do not influence cardiovascular changes in this type of surgery. LAVC can be safely used in hypertensive patients and does not increase the risk of arrhythmias or cardiac ischemia.


Long-lasting reductions of spasticity induced by skin electrical stimulation.
We studied the effects of electrical stimulation of the skin on upper extremity spasticity in nine hemiparetic stroke subjects. The effects were quantified by comparing reflex torque responses elicited during ramp and hold angular perturbations of the elbow recorded before and after low-intensity skin stimulation. Electrical stimulation was applied to skin over the biceps muscle for a period of ten minutes at a 20 Hz frequency, pulse duration 0.1 ms, with an intensity level below motor threshold but above sensory threshold. In seven of the nine subjects, stimulation of skin over spastic muscle reduced peak torque responses in both flexors and extensors for at least 30 min. In these seven subjects there were significant increases in mean threshold angle for the onset of reflex torque so that a greater angular rotation was required to initiate the stretch reflex response. This shift occurred without change in reflex impedance. The origins of these long-term changes in reflex torque are unclear, but may reflect synaptic plasticity of spinal circuitry outside the stretch reflex loop.


Conformational and biological properties of di[delta-(5-nitro-2-pyrimidyl)ornithine 17,18]glucagon. Role of the arginine residues.
The reaction of nitromalondialdehyde with the arginine residues of glucagon results in the conversion of the 2 arginine residues in the peptide to delta-(5-nitro-2-pyrimidyl)ornithine to form di[delta-(5-nitro-2-pyrimidyl)ornithine 17,18]glucagon (NP-glucagon). The modified peptide does not exhibit any loss in ability to activate adenylate cyclase of rat liver plasma membranes or to stimulate glycogenolysis in cortisone-primed rabbits relative to the native hormone despite this marked alteration in structure. The CD of dilute solutions of NP-glucagon is similar to that of the native hormone. In the absence of salt, the CD of NP-glucagon is independent of peptide concentration, but structures of higher helical content are observed in concentrated peptide solutions in the presence of 0.1 M NaCl and in methanol. The extent of helix formation under these conditions is greater than that given by glucagon. Results from viscosity and proton magnetic resonance spectra confirm and extend previous studies to indicate that this fully active derivative is in a compact folded conformation.


Atlantic salmon and sea trout display synchronised smolt migration relative to linked environmental cues.
Anadromous salmon and sea trout smolts face challenging migrations from freshwater to the marine environment characterised by high mortality. Therefore, the timing of smolt migration is likely to be critical for survival. Time-series comparing migration of Atlantic salmon and sea trout smolts in the same river, and their response to the same environmental cues, are scarce. Here, we analysed migration timing of ~41 000 Atlantic salmon and sea trout smolts over a 19-year period from the river Guddalselva, western Norway. Trout displayed a longer migration window in earlier years, which decreased over time to become more similar to the salmon migration window. On average, salmon migrated out of the river earlier than trout. Migration of both species was significantly influenced by river water temperature and water discharge, but their relative influence varied across the years. On average, body-length of smolts of both species overlapped, however, size differences were observed within the migration period and among the years. We conclude that salmon and trout smolts in this river are highly synchronised and migrate in response to the same range of linked environmental cues.


Investigating the regulation of one-carbon metabolism in Arabidopsis thaliana.
Serine (Ser) biosynthesis in C(3) plants can occur via several pathways. One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 184.108.40.206) and serine hydroxymethyltransferase (SHMT, EC 126.96.36.199) with glycine (Gly) as one-carbon (1-C) source. An alternative THF-dependent pathway involves the C1-THF synthase/SHMT activities with formate as 1-C source. Here, we have investigated aspects of the regulation of these two folate-mediated pathways in Arabidopsis thaliana (L.) Heynh. Columbia using two approaches. Firstly, transgenic plants overexpressing formate dehydrogenase (FDH, EC 220.127.116.11) were used to continue our previous studies on the function of FDH in formate metabolism. The formate pool size was approximately 73 nmol (g FW)(-1) in wild type (WT) Arabidopsis plants; three independent transgenic lines had similar-sized pools of formate. Transgenic plants produced more (13)CO(2) from supplied [(13)C]formate than did WT plants but were not significantly different from WT plants in their synthesis of Ser. We concluded that FDH has no direct role in the regulation of the above two pathways of Ser synthesis; the breakdown of formate to CO(2) by the FDH reaction is the primary and preferred fate of the organic acid in Arabidopsis. The ratio between the GDC/SHMT and C1-THF synthase/SHMT pathways of Ser synthesis from [alpha-(13)C]Gly and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1. In shoots, therefore, the pathway from formate plays only a small role in Ser synthesis; in the case of roots, results indicated that the 9 : 1 ratio was as a result of greater fluxes of (13)C through both pathways together with a relatively higher contribution from the C1-THF synthase/SHMT route than in shoots. We also examined the synthesis of Ser in a GDC-deficient mutant of Arabidopsis (glyD) where the GDC/SHMT pathway was impaired. Compared with WT, glyD plants accumulated 5-fold more Gly than WT after supplying [alpha-(13)C]Gly for 24 h; the accumulation of Ser from [alpha-(13)C]Gly was reduced by 25% in the same time period. On the other hand, the accumulation of Ser through the C1-THF synthase/SHMT pathway in glyD plants was 2.5-fold greater than that in WT plants. Our experiments confirmed that the GDC/SHMT and C1-THF synthase/SHMT pathways normally operate independently in Arabidopsis plants but that when the primary GDC/SHMT pathway is impaired the alternative C1-THF synthase/SHMT pathway can partially compensate for deficiencies in the synthesis of Ser.


Alpha-crystallin mutations alter lens metabolites in mouse models of human cataracts.
Cataracts are a major cause of blindness worldwide and commonly occur in individuals over 70 years old. Cataracts can also appear earlier in life due to genetic mutations. The lens proteins, αA- and αB-crystallins, are chaperone proteins that have important roles maintaining protein solubility to prevent cataract formation. Mutations in the CRYAA and CRYAB crystallin genes are associated with autosomal dominant early onset human cataracts. Although studies about the proteomic and genomic changes that occur in cataracts have been reported, metabolomics studies are very limited. Here, we directly investigated cataract metabolism using gas-chromatography-mass spectrometry (GC-MS) to analyze the metabolites in adult Cryaa-R49C and Cryab-R120G knock-in mouse lenses. The most abundant metabolites were myo-inositol, L-(+)-lactic acid, cholesterol, phosphate, glycerol phosphate, palmitic and 9-octadecenoic acids, α-D-mannopyranose, and β-D-glucopyranose. Cryaa-R49C knock-in mouse lenses had a significant decrease in the number of sugars and minor sterols, which occurred in concert with an increase in lactic acid. Cholesterol composition was unchanged. In contrast, Cryab-R120G knock-in lenses exhibited increased total amino acid content including valine, alanine, serine, leucine, isoleucine, glycine, and aspartic acid. Minor sterols, including cholest-7-en-3-ol and glycerol phosphate were decreased. These studies indicate that lenses from Cryaa-R49C and Cryab-R120G knock-in mice, which are models for human cataracts, have unique amino acid and metabolite profiles.


Systemic and Local Cytokine Profile in Biliary Atresia.
Purpose Systemic and local immune environments in human biliary atresia (BA) were analyzed. Methods Plasma concentrations of 19 inflammatory components in 16 preoperative BA patients (median age, 51 days), 13 normal controls (NCs) (44 days), and 15 cholestatic controls (CC) (23 days) were measured using flow cytometry, and compared according to post-Kasai outcomes in BA patients. Hepatic mRNA levels of representative helper T (Th) cell cytokines and forkhead box protein 3 (FoxP3) quantified by real-time reverse transcription polymerase chain reaction were compared between BA and non-BA. Results No significant differences were observed between BA and control in serum Th1, Th2, or macrophage markers, while soluble cellular adhesion molecule (CAM) levels were significantly higher in BA (p < 0.0001 for NC; p = 0.0003 for CC). No statistically significant difference was discovered between BA with favorable and unfavorable prognosis. Hepatic mRNA levels of interferon-gamma or interleukin-4 showed no significant differences between BA and non-BA, while FoxP3 was significantly higher in BA (p = 0.01). Conclusions A skewed bias toward specific Th-oriented immunity was not demonstrated in either the systemic or local environment in the early stage of human BA, with patient prognoses not necessarily revealed by preoperative plasma inflammatory component levels. CAM and regulatory T cell roles and functions warrant further investigation.


Fracture, bone mineral density, and the effects of calcitonin receptor gene in postmenopausal Koreans.
In a candidate gene association study, we found that the variations of calcitonin receptor (CALCR) gene were related to the risk of vertebral fracture and increased bone mineral density (BMD). Calcitonins through calcitonin receptors inhibit osteoclast-mediated bone resorption and modulate calcium ion excretion by the kidney and also prevent vertebral bone loss in early menopause. To identify genetically susceptible factors of osteoporosis, we discovered the variations in CALCR gene, genotyped in Korean postmenopausal women (n = 729), and examined the potential involvement of seven single-nucleotide polymorphism (SNPs) and their haplotypes in linkage disequilibrium block (BL_hts). The SNPs, +43147G > C (intron 7), +60644C > T (exon13, 3' untranslated region), and their haplotypes, BL2_ht1 and BL2_ht2, showed a significant association with risk of vertebral fracture (p = 0.048-0.004) and BL2_ht1 showed a highly significant protective effect. Moreover, the polymorphism +60644C > T showed a highly significant association with BMD at both lumbar spine and femoral neck. The subjects carrying CC and CT genotypes with the SNP, +60644C > T, had higher BMD values at the lumbar spine (p = 0.01-0.001) and femoral neck (p = 0.025-0.009). These results indicate that the CALCR gene may regulate bone metabolism, and +60644C > T in the CALCR gene may genetically modulate bone phenotype.


Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment.
Schizophrenia is frequently a chronic and disabling disorder, characterized by heterogeneous positive and negative symptom constellations. The objective of this review was to provide information that may be useful for clinicians treating patients with negative symptoms of schizophrenia. Negative symptoms are a core component of schizophrenia that account for a large part of the long-term disability and poor functional outcomes in patients with the disorder. The term negative symptoms describes a lessening or absence of normal behaviors and functions related to motivation and interest, or verbal/emotional expression. The negative symptom domain consists of five key constructs: blunted affect, alogia (reduction in quantity of words spoken), avolition (reduced goal-directed activity due to decreased motivation), asociality, and anhedonia (reduced experience of pleasure). Negative symptoms are common in schizophrenia; up to 60% of patients may have prominent clinically relevant negative symptoms that require treatment. Negative symptoms can occur at any point in the course of illness, although they are reported as the most common first symptom of schizophrenia. Negative symptoms can be primary symptoms, which are intrinsic to the underlying pathophysiology of schizophrenia, or secondary symptoms that are related to psychiatric or medical comorbidities, adverse effects of treatment, or environmental factors. While secondary negative symptoms can improve as a consequence of treatment to improve symptoms in other domains (ie, positive symptoms, depressive symptoms or extrapyramidal symptoms), primary negative symptoms generally do not respond well to currently available antipsychotic treatment with dopamine D2 antagonists or partial D2 agonists. Since some patients may lack insight about the presence of negative symptoms, these are generally not the reason that patients seek clinical care, and clinicians should be especially vigilant for their presence. Negative symptoms clearly constitute an unmet medical need in schizophrenia, and new and effective treatments are urgently needed.


Scutellaria baicalensis georgi is a promising candidate for the treatment of autoimmune diseases.
Autoimmune diseases a group of disorders elicited by unexpected outcome of lymphocytes self-tolerance failure, and the common members of which include multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, and type 1 diabetes mellitus, etc. The pathogenesis of autoimmune diseases is not fully understood and the current therapeutic regimen's inefficacy in certain cases coupled with low rates of success, exorbitant financial burden, as well as numerous side effects, which do open new avenues for the role of natural products as novel therapeutic agents for auto-inflammatory disorders. Scutellaria baicalensis Georgi is a well-known and widely-recognized herbal medicine with certain ameliorative effect on diverse inflammation-involved dysfunction. Though recent advances do highlight its potential to be applied in the fight against autoimmune diseases, the specific mechanism and the related opinion on the exploring possibility are still limited which hampered the further progress. Here in this timeline review, we traced and collected the evidence of how Scutellaria baicalensis Georgi and its bioactive contents, namely baicalin, baicalein, wogonoside and wogonin affect autoimmune diseases. Moreover, we also discussed the clinical implications and therapeutic potential of Scutellaria baicalensis Georgi and its bioactive contents in autoimmune diseases treatment.


Intracellular signal transduction pathways activated by ceramide and its metabolites.
The sphingolipid ceramide has proven to be a powerful second-signal effector molecule that regulates diverse cellular processes including apoptosis, cell senescence, the cell cycle, and cellular differentiation. Ceramide has been shown to activate a number of enzymes involved in stress signaling cascades including both protein kinases and protein phosphatases. Ceramide kinase targets include stress-activated protein kinases (SAPKs) such as the jun kinases (JNKs), kinase suppressor of Ras (KSR), and the atypical protein kinase C (PKC) isoform, PKC zeta. Ceramide also is capable of activating protein phosphatases such as protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). It is through these protein phosphatases that ceramide can indirectly inhibit kinases that are key components of pro-growth signaling processes such as the classical and novel PKC isoforms and protein kinase B (PKB; also known as Akt). However, the mechanisms how ceramide directly activates enzymes such as JNK and PP2A are still not clear. Elucidation of these mechanisms will reveal how ceramide functions in stress signaling cascades and will provide important information on cellular processes such as apoptosis. It is becoming clear that the ceramide generation is a near universal feature of programmed cell death. It is possible that during at least some apoptotic events, ceramide may be required to activate stress-signal cascades that lead to cell death, while concurrently, suppressing growth and survival pathways in the dying cell. Such a versatile role for ceramide is not unreasonable since ceramide has been implicated as having a role in both intrinsic (i.e. mitochondrial) and extrinsic (i.e. death receptor-mediated) apoptotic pathways. The recent data suggesting that aberrant glycosylation of ceramide (i.e. inactivation of the molecule) may be an important cause of drug resistance in certain cancers suggests that ceramide-mediated signaling cascades are critical components of chemotherapy-induced cell killing. Taken together, these properties of ceramide suggest that this important second-signal molecule may be an important target in anti-neoplastic strategies.


Sox10--a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors.
Sox10 transcription factor is expressed in schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. In addition, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 expression in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30 to 70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the gastrointestinal tract and in metastatic melanoma and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, perivascular epithelioid cell tumor and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell-type breast cancers, were only rarely positive but included 6% of squamous carcinomas of head and neck and 7% of pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.


Mechanisms of dexamethasone-induced disturbed sleep and fatigue in paediatric patients receiving treatment for ALL.
Dexamethasone contributes to high cure rates in paediatric acute lymphoblastic leukaemia (ALL) but significantly and adversely alters sleep and fatigue. Herein we explored three mechanisms (pharmacokinetics, serum albumin and pharmacogenetics) through which dexamethasone may cause debilitating fatigue and disrupted sleep. We enrolled 100 patients on a 10-d study: 5-d of no dexamethasone (OFF DEX) followed by 5-d of dexamethasone (ON DEX) during continuation chemotherapy. Sleep variables were collected with continuous actigraphy on days 1 through 5, both OFF DEX and ON DEX. On days 2 and 5 of each 5-d period, parents and patients 7 years of age and older completed a sleep diary and Fatigue Scale questionnaire. Blood was collected at 0 (pre-dexamethasone), 1, 2, 4 and 8 h after the first oral dexamethasone dose for pharmacokinetic analysis. Serum albumin concentration was retrospectively analysed in stored samples. Patient DNA was genotyped for 99 polymorphic loci in candidate genes associated with glucocorticoid metabolism. Dexamethasone clearance was significantly greater in younger patients than in older ones and in lower risk patients. In multiple regression models, risk group was significantly related to pharmacokinetic parameters. We found that polymorphisms in three genes (AHSG, IL6, POLDIP3) were significantly associated with sleep measures but not with fatigue. Risk group had the most significant relationship with disrupted sleep in patients while on dexamethasone. Serum albumin levels had neither a direct relationship with sleep or fatigue variables nor an indirect relationship through systemic exposure to dexamethasone. We identified candidate genes that may help explain the adverse events of disrupted sleep in paediatric patients receiving dexamethasone.


Advice for Junior Faculty Regarding Academic Promotion: What Not to Worry About, and What to Worry About.
Junior faculty in many universities must go through the promotion process to advance from entry level, e.g., assistant professorship to associate Professor, and ultimately to professorship. The process may often be stressful for some junior faculty, mostly due to some uncertainty about how to optimise their chances of successful promotion. In this paper, we summarise some strategies that would enhance their chances of a smooth promotion based on experiences from junior faculty and senior faculty who have served on tenure and promotion committees. These strategies include understanding the promotion process at your institution; optimizing publications as first or senior author, securing research funding as principal investigator, teaching effectively, providing service efficiently; developing good time management and priority setting skills, finding excellent mentors, and targeting opportunities for collaboration. We also encourage junior faculty to be pro-active about promotion.


A common origin of rickettsiae and certain plant pathogens.
On the basis of ribosomal RNA sequence comparisons, the rickettsia Rochalimaea quintana has been found to be a member of subgroup 2 of the alpha subdivision of the so-called purple bacteria, which is one of about ten major eubacterial divisions. Within subgroup alpha-2, R. quintana is specifically related to the agrobacteria and rhizobacteria, organisms that also have close associations with eukaryotic cells. This genealogical grouping of the rickettsiae with certain plant pathogens and intracellular symbionts suggests a possible evolution of the rickettsiae from plant-associated bacteria.


Responding to COVID-19: Establishing a nursing system that is appropriate for the new post-epidemic era.
Hospitals that admit patients with COVID-19 face the challenge of not only dealing with these patients but also balancing normal medical care and hospital management to cope with the challenges posed by the new post-epidemic era. Over the past two years of responding to COVID-19 as a front-line clinical nurse, my colleagues and I have fully appreciated the need to establish a nursing system that is appropriate for the new post-epidemic era. The following four aspects should be emphasized: i) the continuation of thorough infection control measures; ii) exploring new approaches to training for new recruits; iii) ensuring nursing workforce and improving the nursing capacity to cope with patients critically ill with COVID-19; and iv) teamwork and team care to provide nurses with timely psychological assistance.


Proximal Plantar Intrinsic Tendinopathy: Anatomical and Biomechanical Considerations in Plantar Heel Pain.
Plantar heel pain is often managed through podiatric and physical therapy interventions. Numerous differential diagnoses may be implicated in patients presenting with plantar heel pain; however, symptoms are often attributed to plantar fasciitis. Abductor hallucis, flexor digitorum brevis, and quadratus plantae share proximal anatomic attachment sites and mechanical function with the plantar fascia. Although these plantar intrinsic muscles each perform isolated digital actions based on fiber orientation and attachment sites, they function collectively to resist depression of the lateral and medial longitudinal arches of the foot. Overuse injury is the primary contributing factor in tendinopathy. The close anatomic proximity and mechanical function of these muscles relative to the plantar fascia suggests potential for proximal plantar intrinsic tendinopathy as a result of repetitive loading during gait and other weightbearing activities. To date, this diagnosis has not been proposed in the scientific literature. Future studies should seek to confirm or refute the existence of proximal plantar intrinsic tendinopathic changes in patients with acute and chronic plantar heel pain through diagnostic imaging studies, analysis of lactate concentration in pathologic versus nonpathologic tendons, and response to specific podiatric and physical therapy interventions germane to tendinopathy of these muscles.


Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation.
During the administration of advanced cardiac life support for resuscitation from cardiac arrest, a combination of vasopressin and epinephrine may be more effective than epinephrine or vasopressin alone, but evidence is insufficient to make clinical recommendations. In a multicenter study, we randomly assigned adults with out-of-hospital cardiac arrest to receive successive injections of either 1 mg of epinephrine and 40 IU of vasopressin or 1 mg of epinephrine and saline placebo, followed by administration of the same combination of study drugs if spontaneous circulation was not restored and subsequently by additional epinephrine if needed. The primary end point was survival to hospital admission; the secondary end points were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival. A total of 1442 patients were assigned to receive a combination of epinephrine and vasopressin, and 1452 to receive epinephrine alone. The treatment groups had similar baseline characteristics except that there were more men in the group receiving combination therapy than in the group receiving epinephrine alone (P=0.03). There were no significant differences between the combination-therapy and the epinephrine-only groups in survival to hospital admission (20.7% vs. 21.3%; relative risk of death, 1.01; 95% confidence interval [CI], 0.97 to 1.05), return of spontaneous circulation (28.6% vs. 29.5%; relative risk, 1.01; 95% CI, 0.97 to 1.06), survival to hospital discharge (1.7% vs. 2.3%; relative risk, 1.01; 95% CI, 1.00 to 1.02), 1-year survival (1.3% vs. 2.1%; relative risk, 1.01; 95% CI, 1.00 to 1.02), or good neurologic recovery at hospital discharge (37.5% vs. 51.5%; relative risk, 1.29; 95% CI, 0.81 to 2.06). As compared with epinephrine alone, the combination of vasopressin and epinephrine during advanced cardiac life support for out-of-hospital cardiac arrest does not improve outcome. (ClinicalTrials.gov number, NCT00127907.)


440-kD ankyrinB: structure of the major developmentally regulated domain and selective localization in unmyelinated axons.
440-kD ankyrinB is an alternatively spliced variant of 220-kD ankyrinB, with a predicted 220-kD sequence inserted between the membrane/spectrin binding domains and COOH-terminal domain (Kunimoto, M., E. Otto, and V. Bennett. 1991. J. Cell Biol. 236:1372-1379). This paper presents the sequence of 2085 amino acids comprising the alternatively spliced portion of 440-kD ankyrinB, and provides evidence that much of the inserted sequence has the configuration of an extended random coil. Notable features of the inserted sequence include a hydrophilicity profile that contains few hydrophobic regions, and 220 predicted sites for phosphorylation by protein kinases (casein kinase 2, protein kinase C, and proline-directed protein kinase). Secondary structure and folding of the inserted amino acid residues were deduced from properties of recombinant polypeptides. Frictional ratios of 1.9-2.4 were calculated from Stokes radii and sedimentation coefficients, for polypeptides comprising 70% of the inserted sequence, indicating a highly asymmetric shape. Circular dichroism spectra of these polypeptides indicate a nonglobular structure with negligible alpha-helix or beta sheet folding. These results suggest a ball-and-chain model for 440-kD ankyrinB with a membrane-associated globular head domain and an extended filamentous tail domain encoded by the inserted sequence. Immunofluorescence and immunoblot studies of developing neonatal rat optic nerve indicate that 440-kD ankyrinB is selectively targeted to premyelinated axons, and that 440-kD ankyrinB disappears from these axons coincident with myelination. Hypomyelinated nerve tracts of the myelin-deficient Shiverer mice exhibit elevated levels of 440-kD ankyrinB. 440-kD ankyrinB thus is a specific component of unmyelinated axons and expression of 440-kD ankyrinB may be downregulated as a consequence of myelination.


Executive Functioning and Self-Management Processes Mediate the Relationship Between Insomnia and Pain-Related Disability.
Insomnia has been identified as a predictor of reduced benefit from cognitive-behavioral treatment (CBT) for adolescent chronic pain; however, it is not well understood how insomnia leads to reduced treatment response. The purpose of this study was to evaluate executive function and self-management processes as 2 potential mediators of the relationship between insomnia symptoms and pain-related disability outcomes from internet-delivered CBT using a single-arm clinical trial design. Eighty-five adolescents with chronic pain (77% female, ages 12-17 years) and their caregiver received an 8-week internet-delivered CBT intervention. Youth completed validated measures of insomnia symptoms, executive function, self-management processes, and pain-related disability at baseline, mid-treatment, immediate post-treatment, and 3-month follow-up. Results from multilevel structural equation modeling indicated that more severe insomnia symptoms were associated with greater problems with executive function, which, in turn, led to lower engagement in self-management processes and less improvement in pain-related disability. These findings identify 2 mediators by which higher insomnia symptoms may lead to reduced benefit from CBT intervention for chronic pain. Research is needed to understand whether psychological treatments for chronic pain may be optimized by strategies targeting insomnia, executive function, and/or engagement in self-management. This trial was registered at clinicaltrials.gov (NCT04043962). PERSPECTIVE: Our study suggests that executive functioning and self-management processes mediate the relationship between insomnia and treatment outcomes for pediatric chronic pain, highlighting the impact of insomnia on youth learning and implementation of self-management strategies and the critical need for targeted sleep interventions in this population.


Comparative studies on mammalian Hoxc8 early enhancer sequence reveal a baleen whale-specific deletion of a cis-acting element.
Variations in regulatory regions of developmental control genes have been implicated in the divergence of axial morphologies. To find potentially significant changes in cis-regulatory regions, we compared nucleotide sequences and activities of mammalian Hoxc8 early enhancers. The nucleotide sequence of the early enhancer region is extremely conserved among mammalian clades, with five previously described cis-acting elements, A-E, being invariant. However, a 4-bp deletion within element C of the Hoxc8 early enhancer sequence is observed in baleen whales. When assayed in transgenic mouse embryos, a baleen whale enhancer (unlike other mammalian enhancers) directs expression of the reporter gene to more posterior regions of the neural tube but fails to direct expression to posterior mesoderm. We suggest that regulation of Hoxc8 in baleen whales differs from other mammalian species and may be associated with variation in axial morphology.


A novel Mg(2+)-dependent O-methyltransferase in the phenylpropanoid metabolism of Mesembryanthemum crystallinum.
Upon irradiation with elevated light intensities, the ice plant (Mesembryanthemum crystallinum) accumulates a complex pattern of methylated and glycosylated flavonol conjugates in the upper epidermal layer. Identification of a flavonol methylating activity, partial purification of the enzyme, and sequencing of the corresponding peptide fragments revealed a novel S-adenosyl-l-methionine-dependent O-methyltransferase that was specific for flavonoids and caffeoyl-CoA. Cloning and functional expression of the corresponding cDNA verified that the new methyltransferase is a multifunctional 26.6-kDa Mg(2+)-dependent enzyme, which shows a significant sequence similarity to the cluster of caffeoyl coenzyme A-methylating enzymes. Functional analysis of highly homologous members from chickweed (Stellaria longipes), Arabidopsis thaliana, and tobacco (Nicotiana tabacum) demonstrated that the enzymes from the ice plant, chickweed, and A. thaliana possess a broader substrate specificity toward o-hydroquinone-like structures than previously anticipated for Mg(2+)-dependent O-methyltransferases, and are distinctly different from the tobacco enzyme. Besides caffeoyl-CoA and flavonols, a high specificity was also observed for caffeoylglucose, a compound never before reported to be methylated by any plant O-methyltransferase. Based on phylogenetic analysis of the amino acid sequence and differences in acceptor specificities among both animal and plant O-methyltransferases, we propose that the enzymes from the Centrospermae, along with the predicted gene product from A. thaliana, form a novel subclass within the caffeoyl coenzyme A-dependent O-methyltransferases, with potential divergent functions not restricted to lignin monomer biosynthesis.


MR imaging of the pericardium.
Imaging of the pericardium requires understanding of anatomy and the normal and abnormal physiology of the pericardium. MR imaging is well-suited for answering clinical questions regarding suspected pericardial disease. Pericardial diseases that may be effectively imaged with MR imaging include pericarditis, pericardial effusion, cardiac-pericardial tamponade, constrictive pericarditis, pericardial cysts, absence of the pericardium, and pericardial masses. Although benign and malignant primary tumors of the pericardium may be occasionally encountered, the most common etiology of a pericardial mass is metastatic disease.


Whole genome identification of olive flounder (Paralichthys olivaceus) cathepsin genes: Provides insights into its regulation on biotic and abiotic stresses response.
Cathepsins are major lysosomal enzymes involved in essential physiological processes, including protein degradation, tissue differentiation, and innate or adaptive responses. Several kinds of cathepsins have been reported in teleost fishes, but no characterization have been performed for the inflammatory response of cathepsin family in olive flounder until now. In our current study, a total of 17 cathepsins in olive flounder were systematically identified and characterized. Phylogenetic analysis clearly indicated that the cathepsin genes was highly conserved. Analysis of structure and motifs exhibited high sequence similarity of cathepsin genes in olive flounder. Expression profiles of cathepsin genes in different tissues and developmental stages showed that cathepsins were temporally and spatially specific. RNA-seq analysis of bacteria and temperature stresses revealed that members of cathepsin were involved in inflammatory responses. Collectively, our findings would provide a further reference for understanding the molecular mechanisms of cathepsins in olive flounder.


[An adult case of Leigh's subacute necrotizing encephalomyelopathy].
Leigh's encephalomyelopathy has been mainly observed in infancy and childhood. A later onset, during adolescence or adulthood has been rarely reported. Our patient was a 35 year-old man who died after 10 months of evolution of a subacute neurological syndrome, beginning with behavioural changes then a confusional state, epileptic fits, ataxia, autonomic disorders, abnormal alimentary behaviour and dementia. Diagnosis was only obtained by neuropathology, as in most of the published reports. However this diagnosis is suggested when exists an acute or subacute neurological pattern, beginning with visual defects and alimentary and social impairment, followed by a brain-stem syndrome. CT and M.R.I. will make it more easy. An earlier diagnosis could perhaps allow to discover the suspected enzymopathy responsible for Leigh's encephalomyelopathy and make clearer the relationship between Leigh's disease and encephalopathies with abnormal mitochondria.


A Review of the Benefits of Nature Experiences: More Than Meets the Eye.
Evidence that experiences of nature can benefit people has accumulated rapidly. Yet perhaps because of the domination of the visual sense in humans, most research has focused on the visual aspects of nature experiences. However, humans are multisensory, and it seems likely that many benefits are delivered through the non-visual senses and these are potentially avenues through which a physiological mechanism could occur. Here we review the evidence around these lesser studied sensory pathways-through sound, smell, taste, touch, and three non-sensory pathways. Natural sounds and smells underpin experiences of nature for many people, and this may well be rooted in evolutionary psychology. Tactile experiences of nature, particularly beyond animal petting, are understudied yet potentially fundamentally important. Tastes of nature, through growing and consuming natural foods, have been linked with a range of health and well-being benefits. Beyond the five senses, evidence is emerging for other non-visual pathways for nature experiences to be effective. These include ingestion or inhalation of phytoncides, negative air ions and microbes. We conclude that (i) these non-visual avenues are potentially important for delivering benefits from nature experiences; (ii) the evidence base is relatively weak and often based on correlational studies; and (iii) deeper exploration of these sensory and non-sensory avenues is needed.


Uncovering the hydride ion diffusion pathway in barium hydride via neutron spectroscopy.
Solid state materials possessing the ability for fast ionic diffusion of hydrogen have immense appeal for a wide range of energy-related applications. Ionic hydrogen transport research is dominated by proton conductors, but recently a few examples of hydride ion conductors have been observed as well. Barium hydride, BaH2, undergoes a structural phase transition around 775 K that leads to an order of magnitude increase in the ionic conductivity. This material provides a prototypical system to understand hydride ion diffusion and how the altered structure produced by the phase transition can have an enormous impact on the diffusion. We employ quasielastic and inelastic neutron scattering to probe the atomic scale diffusion mechanism and vibrational dynamics of hydride ions in both the low- and high-temperature phases. Jump lengths, residence times, diffusion coefficients, and activation energies are extracted and compared to the crystal structure to uncover the diffusion pathways. We find that the hydrogen jump distances, residence times, and energy barriers become reduced following the phase transition, allowing for the efficient conduction of hydride ions through a series of hydrogen jumps of length L = 3.1 Å.


Toward a comprehensive developmental model for major depression in women.
Major depression is a multifactorial disorder with many etiologic variables that are interrelated through developmental pathways. The authors used structural equation modeling to generate a developmental model for the etiology of major depression in women. Data from 1,942 adult female twins, interviewed up to four times over a 9-year period, were used to construct a developmental model to predict depressive episodes in the year before the most recent interview. Eighteen risk factors in five developmental tiers were considered: 1) childhood (genetic risk, disturbed family environment, childhood sexual abuse, and childhood parental loss), 2) early adolescence (neuroticism, self-esteem, and early-onset anxiety and conduct disorder), 3) late adolescence (educational attainment, lifetime traumas, social support, and substance misuse), 4) adulthood (history of divorce and past history of major depression), and 5) the last year (marital problems, difficulties, and stressful life events). The best fitting model included six correlations and 64 paths, provided an excellent fit to the data, and explained 52% of the variance in liability to episodes of major depression. The findings suggest that the development of risk for major depression in women results from three broad pathways reflecting internalizing symptoms, externalizing symptoms, and psychosocial adversity. Major depression is an etiologically complex disorder, the full understanding of which will require consideration of a broad array of risk factors from multiple domains. These results, while plausible, should be treated with caution because of problems with causal inference, retrospective recall bias, and the limitations of a purely additive statistical model.


[Effect of the antiemetic preparation dimetpramid on rat reproductive function].
It has been demonstrated that dimethpramide exerted an adverse effect on the sexual glands of female rats. It provoked an inhibition of ovarian function (derangement of cycling rhythmicity, the loss of individual cycle stages) and depletion of energy resources of the uterus (drop of glycogen content). The reduction of the gonadotropic activity of the pituitary was also observed.


Intratendinous tears of the Achilles tendon - a new pathology? Analysis of a large 4-year cohort.
Achillodynia is common and includes Achilles tendinopathy, partial Achilles tears and Achilles tendon ruptures. However, we believe an additional pathology should be considered for Achillodynia differentials - the intratendinous tear (ITT). Examinations of 740 achillodynic patients in one specialist centre were reviewed. ITTs were defined as a clearly visualised echopoor area situated centrally and extending to, but not through the tendon periphery, with pain on palpation and no clinical findings consistent with Achilles rupture. Descriptive statistics were used to analyse differences between pathological sub-groups, and images described qualitatively. 5% (29 males, 8 females) of 740 patients had an ITT. Patients typically presented with a history of sudden onset localised pain and the ability to train but not reach maximal loading. Average age was 36.3 years (range 20-64), significantly lower than mid-tendon tendinopathy (8.48 years; p<0.01). 92% had concurrent Achilles tendinopathy. Elite sportspeople were more highly represented in the ITT than mid-tendon tendi nopathy groups (86.2% ITT group vs 13.8% mid-tendon AT group; p<0.01). ITTs should be actively searched for in patients with Achilles pathology, especially in elite male athletes with a history of high-impact pain. Prospective research is warranted concerning diagnosis and management. IV.


Transferability and utility of white oat (Avena sativa) microsatellite markers for genetic studies in black oat (Avena strigosa).
Preservation and use of wild oat species germplasm are essential for further improvement of cultivated oats. We analyzed the transferability and utility of cultivated (white) oat Avena sativa (AACCDD genome) microsatellite markers for genetic studies of black oat A. strigosa (A(s)A(s) genome) genotypes. The DNA of each black oat genotype was extracted from young leaves and amplified by PCR using 24 microsatellite primers developed from white oat. The PCR products were separated on 3% agarose gel. Eighteen microsatellite primer pairs amplified consistent products and 15 of these were polymorphic in A. strigosa, demonstrating a high degree of transferability. Microsatellite primer pairs AM3, AM4, AM21, AM23, AM30, and AM35 consistently amplified alleles only in A. sativa, which indicates that they are putative loci for either the C or D genomes of Avena. Using the data generated by the 15 polymorphic primer pairs, it was possible to separate 40 genotypes of the 44 that we studied. The four genotypes that could not be separated are probably replicates. We conclude that A. sativa microsatellites have a high transferability index and are a valuable resource for genetic studies and characterization of A. strigosa genotypes.


[Fluorescence angiography in the diagnosis of pathology of the fundus oculi in children].
Fluorescent diagnostics examinations were undertaken by the authors in different-age 410 children. The peroral fluorescent angiography (FAG) was used to examine 20% of cases, and the intravenous FAG was applied to 80% of cases. We offered the differential approach to dosing the solution, while making the peroral FAG examinations, which reduces the frequency rate of unfavorable reactions. The dosage ranged from 20 to 25 mg/kg with regard for purposes of examinations. The use of fluorescein did not cause any serious complications; nausea and a short faintness state were registered only in 10% of children. An examination of angiography images demonstrated that the phases of tinting of healthy tissue were identical to those tinted at the intravenous FAG. The below peculiarities of the child eye fundus were established: a weaker, as compared to the adults, pigmentation of the eye fundus, an insufficient differentiation of the macular zone and an immature peripheral retina in children during the neonatal period. Indications for FAG at congenital and acquired eye pathologies are specified.


An Evolutionary Approach to Binge Drinking Impression Formation: A Cross-Cultural Comparison Between France and Peru.
Evolutionary medicine proposes studying alcohol use and abuse through the lens of modern evolutionary theory. This study ( https://osf.io/p48 uw/) follows this approach and uses an evolutionary framework to predict how young adults (18-35 years old) form impression of a binge drinker. We predicted that displaying sexual dysfunctions (short-term risk) in a binge drinking video would negatively influence attitudes and expectations of a target when compared to cognitive (short-term risk) or long-term deficits. In the following studies, we use a Zahavian framework to understand and influence impression formation of a male binge drinker among women (intersexual selection) and men (intrasexual competition) participants in a subsequent task. Via a randomized experimental online study in France (N = 177, M = 23.39 [4.91], 43.50% men) and a preregistered conceptual replication study in Peru (N = 176, M = 25.61 [4.76], 53.41% men), women exposed to a binge drinking video-describing sexual impotence after a binge drinking episode-tended to downgrade attractiveness evaluation of the binge drinker. However, male participants were not impacted by the different types of signals displayed in the videos. These results show that evolutionary theory could help us understand impression formation in binge drinking context and call for gender-specific health messages.


Early plasma-membrane-potential changes during stimulation of lymphocytes by concanavalin A.
1. We have monitored the plasma-membrane potential of lymphocytes by measuring the accumulation of the lipophilic cation methyltriphenylphosphonium (TPMP+) in the presence of the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). 2. The mitogen concanavalin A causes a decrease in TPMP+ accumulation by pig lymphocytes corresponding to a 3 mV depolarization with 2 1/2 min. Concanavalin A does not alter 86Rb+ uptake in the first 30 min. 3. In contrast concanavalin A increased TPMP+ accumulation and the rate of Rb+ uptake in mouse thymocytes. This is consistent with a previous proposal that the mitogen induces a hyperpolarization of mouse thymocytes as a result of stimulation of a Ca2+-dependent K+ channel. 4. Studies with the calcium ionophore A23187 and quinine (an inhibitor of the Ca2+-dependent K+ channel) suggest that the channel is partially closed in mouse resting thymocytes but is almost fully active in pig resting cells. Thus concanavalin A hyperpolarizes mouse thymocytes by activating the Ca2+-dependent K+ channel but cannot do so in pig lymphocytes because the channel is already maximally activated. 5. The 3mV depolarization of pig cells cannot be explained by a decrease in electrogenic K+ permeability.


A roll-to-roll welding process for planarized silver nanowire electrodes.
We demonstrate continuous roll-to-roll production of highly conductive silver network films on a plastic substrate via mechanical and chemical welding processes. This process included three essential steps: (i) solvent spraying, (ii) roll compression, and (iii) salt treatment and washing. The sheet resistance of the resulting AgNW film was 5 Ω sq(-1) at 92% transmittance, which was the lowest sheet resistance and the highest transparency among the values reported previously for solution-processed AgNW electrodes. Moreover, the strong contacts among the AgNWs dramatically enhanced the mechanical stability of the network film. The resulting AgNW film was successfully applied to various organic electronic devices, such as organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs), and organic solar cells (OSCs).


The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding.
Long term (21-day) treatment with antidepressants induces a decrease in beta-adrenergic and serotonin 2 (5-HT2) receptor binding in rat brain frontal cortex. Since hormone imbalances are known to be associated with affective illness, the present study was undertaken to determine whether sex hormones influence these alterations in neurotransmitter receptor binding. Using receptor binding assays, we found that castration abolishes the decline in the concentration of 5-HT2, but not beta-adrenergic, receptors brought on by chronic imipramine or iprindole treatment in both male and female rats. In contrast, the receptor responses to trazodone, mianserin, and pargyline were not influenced by surgery. Furthermore, mianserin was found to reduce beta-adrenergic binding in intact females, but not males, suggesting a sex-related specificity with regard to the response to this agent. Testosterone and estrogen, but not dihydrotestosterone, reversed the effects of castration in males, suggesting that the interaction between the steroids and antidepressants is mediated through estrogenic, rather than androgenic, receptors. The results indicate that the receptor responses to some antidepressant drugs is dependent, at least in part, on the hormonal state of the animals.


[Comparative characteristics of the adrenal and gonadal functions in human beings and hamadryas baboons with hemoblastosis].
Adrenal and gonad steroid hormones were investigated in the peripheral blood plasma of human beings and hamadryas baboons (Papio hamadryas) with hemoblastosis. The similar hormonal dysfunction of adrenal glands and gonads was found in human beings and monkeys. The dehydroepiandrosterone level was found to decrease significantly, while the cortisol level increased markedly. Changes in the androgen level were sex-dependent. The testosterone and 5 alpha-dihydrotestosterone levels were found to decrease markedly in men and male baboons while the testosterone level in women and females was found to increase significantly with 5 alpha-dihydrotestosterone unchanged.


No Seasonal Changes in Cognitive Functioning Among High School Football Athletes: Implementation of a Novel Electrophysiological Measure and Standard Clinical Measures.
To evaluate neuroelectric and cognitive function relative to a season of football participation. Cognitive and neuroelectric function declines are hypothesized to be present in football athletes. Observational. Athletic fields and research laboratory. Seventy-seven high school athletes (15.9 + 0.9 years, 178.6 + 7.2 cm, 74.4 + 14.7 kg, and 0.8 + 0.8 self-reported concussions) participating in football (n = 46) and noncontact sports (n = 31). All athletes completed preseason, midseason, and postseason assessments of cognitive and neuroelectric function, self-reported symptoms, and quality of life. All athletes participated in their respective sports without intervention, while head impact exposure in football athletes was tracked using the Head Impact Telemetry System. Cognitive performance was based on Cogstate computerized cognitive assessment tool processing speed, attention, learning, working memory speed, and working memory accuracy scores. ElMindA brain network activation amplitude, synchronization, timing and connectivity brain network activation scores demarcated neuroelectric performance. Quality of life was assessed on the Health Behavior Inventory and Satisfaction with Life Scale and symptoms on the SCAT3 inventory. Football and control sport athletes did not show declines in cognitive or neuroelectric function, quality-of-life measures, or symptom reports across a season of sport participation. These findings refute the notion that routine football participation places athletes at risk for acute cognitive declines. The lack of impairment may be associated with no association with head impacts and cognitive function, increased physical activity offsetting any declines, and/or test sensitivity. How these findings are associated with long-term cognitive function is unknown.


Anxiety sensitivity in African-American adolescents: evidence of symptom specificity of anxiety sensitivity components.
To examine the specificity of components of anxiety sensitivity (phrenophobia, fear of cardiovascular sensations, and fear of unsteadiness) to anxiety and depression in a sample of African-American adolescents. Participants were 527 African-American adolescents (238 females, mean age 13.8 years) who were originally recruited as first graders in 1993 to 1994 for participation in the second-generation Johns Hopkins Prevention Intervention Research Center trials. Youths completed measures of anxiety sensitivity and anxious and depressive symptoms in the spring of 2001. Associations between anxiety sensitivity and depression and anxiety were examined using hierarchical linear regressions. Anxiety sensitivity as a unitary construct was positively associated with symptoms of anxiety after adjusting for symptoms of depression. Fear of unsteadiness showed specificity to anxiety after adjusting for depression and phrenophobia. Phrenophobia was positively associated with anxiety and depression, after adjusting for the other symptom and fears of physical sensations. Specificity of anxiety sensitivity to anxiety in a sample of African-American adolescents furthers understanding of the nature of anxiety sensitivity in this group and the potential roles of components of anxiety sensitivity in the development of psychopathology in general.


Tend and befriend in the intensive care unit.
Stress is a common phenomenon in the intensive care unit for both patients and nurses. Critical care nurses may experience many forms of stress, including physical, psychological, and moral stress or distress. The physiological stress response traditionally associated with the hypothalamic-pituitary-adrenal axis has been expanded to include a new model, called tend and befriend, that has been linked to females of different species, including humans. Studies have shown that stress also affects immune function. Although commonly associated with adverse outcomes, stress can lead to personal growth. The tend and befriend strategy is an intervention that was developed to help nurses increase their ability to grow from stressful situations, especially those related to moral distress.


Transpiration sensitivities to evaporative demand and leaf areas vary with night and day warming regimes among wheat genotypes.
Warmer climates are already contributing to significant decreases in wheat (Triticum spp.) yields worldwide, highlighting the need for more adapted germplasm. Although many studies have addressed the effects of warmer climates on grain physiology and photosynthesis, only a few have considered temperature effects on other key yield-related traits such as the sensitivity of transpiration rate (TR) to vapour pressure deficit (VPD)-a function of air temperature and relative humidity. In wheat, no reports are available to document such influences. More importantly, the relative contributions of heat-stress night and day conditions on such sensitivity and the plant's evaporative surface remain to be investigated. The objective of this study was to assess the response of these two physiological processes to long-term (i.e. 3 weeks) exposures to six warming scenarios, consisting of a combination of three target growth-period VPD (2, 2.7 and 4kPa), and two night temperature (20 and 30°C) regimes among 11 diverse bread and durum wheat lines having different origins. The study revealed (i) a large genetic variability in those responses; (ii) non-linear interactions between the effects of day and night conditions; and (iii) compensation mechanisms between leaf areas and transpiration sensitivities to VPD together with differential acclimation strategies of these sensitivities with respect to increasingly warmer scenarios. These findings open the way to implementing breeding strategies that can improve wheat yields under different warming scenarios.


[The influence of neuromodulators on the synaptic plasticity in dopaminergic structures of the midbrain (hypothetical mechanism)].
A mechanism underlying the effects of neuromodulators on long-term changes in the efficacy of excitatory and inhibitory inputs to dopaminergic and inhibitory cells of the substantia nigra and ventral tegmental area is suggested. According to this mechanism, activation of Gi/0 protein-coupled dopamine D2 autoreceptors and opioid kappa (mu) receptors on dopaminergic (inhibitory) cells promotes the LTD of excitatory inputs to these cells and decrease in their activity. Activation of Gq/11 protein-coupled alpha1 adrenoreceptors, muscarinic M1, neurokinin NK3 (alpha1, M3, NK1, serotonin 5-HT2) receptors on dopaminergic (inhibitory) cells as well as activation of Gs protein-coupled D1 receptors on inhibitory cells promotes the LTP of excitatory inputs to these cells and increase in their activity. Augmenting (lowering) GABA release can be provided by activation of presynaptic D1 and M3 receptors (mu, 5-HT1, and adenosine A1) receptors. Increase (decrease) in GABA concentration due to modulation of inhibitory cell activity and/or GABA release will promote the induction of LTD (LTP) of excitatory inputs to target dopamine cells. The model agree with known experimental data describing the involvement of neuromodulators in modification of dopamine cell activity and dopamine release. The suggested model can be useful in understanding the operation of neuronal networks, which include the basal ganglia.


Exploring the Use of Living Shorelines for Stabilization and Nutrient Mitigation in New England.
As salt marsh habitats face challenges due to sea level rise, storm events, and coastal development, there is an effort to use nature-based approaches such as living shorelines to enhance salt marshes and provide coastal protection. A living shoreline restoration and seasonal monitoring was conducted between July 2016 and October 2018 at an eroding salt marsh on Martha's Vineyard, Massachusetts, Northeastern USA to assess changes in two essential ecosystem services: shoreline stabilization and nitrogen removal. Neither the living shoreline nor unaltered sites demonstrated significant sediment deposition at the marsh edge or on the marsh platform between 2017 and 2018. While we expected nitrogen removal via denitrification to improve at the living shoreline sites over time as abiotic and biotic conditions became more favorable, we found limited support for this hypothesis. We found higher rates of denitrification enzyme activity (DEA) at the living shoreline sites when compared to unaltered sites, but these rates did not increase over time. This study also provides a qualitative assessment of our living shoreline structural integrity through the years, particularly following storm events that greatly challenged our restoration efforts. We demonstrate that living shorelines fortified solely with natural materials may not be the most effective approach to maintain these ecosystem services for Northeastern USA salt marshes exposed to intense northeasterly storms. We suggest the restoration of salt marshes to improve major functions be a priority among managers and restoration practitioners. Initiatives promoting the use of nature-based restoration solution where environmental conditions permit should be encouraged.


Muvi schmallenbergi gen. nov., sp. nov. (Crustacea, Tanaidacea) from the southeast Australian coast, with comments on the distribution and habitat preferences of Chondropodinae.
Based on material collected from the shelf off southeast Australia (offshore of Portland), a new genus and new species, Muvi schmallenbergi gen. nov., sp. nov., of the tanaidacean family Metapseudidae, is described. Muvi is distinguishable from other genera within the subfamily Chondropodinae by having equally long antennular flagella. It also differs from other Chondropodinae by a combination of characters such as eyelobes with a group of visual elements, rostrum with smooth lateral edges, pereonites with lateral processes and pleotelson lacking lateral process, antennule article-1 with a single apophysis, maxillule inner lobe well-developed, labial palp bearing three distal setae, cheliped exopod well-developed and setose, pereopod-1 coxa with distinct apophysis, pleopods in five pairs, and uropod basis without apophysis. The genus Deidamiapseudes Sganga & Roccatagliata, 2016 is moved from Chondropodinae (Metapseudidae) to Apseudoidea incertae sedis. An identification key for the genera within Chondropodinae is given, and their distribution is discussed.


Chronic Cannabigerol as an Effective Therapeutic for Cisplatin-Induced Neuropathic Pain.
Cannabigerol (CBG), derived from the cannabis plant, acts as an acute analgesic in a model of cisplatin-induced peripheral neuropathy (CIPN) in mice. There are no curative, long-lasting treatments for CIPN available to humans. We investigated the ability of chronic CBG to alleviate mechanical hypersensitivity due to CIPN in mice by measuring responses to 7 and 14 days of daily CBG. We found that CBG treatment (i.p.) for 7 and 14 consecutive days significantly reduced mechanical hypersensitivity in male and female mice with CIPN and reduced pain sensitivity up to 60-70% of baseline levels (p < 0.001 for all), 24 h after the last injection. Additionally, we found that daily treatment with CBG did not evoke tolerance and did not incur significant weight change or adverse events. The efficacy of CBG was independent of the estrous cycle phase. Therefore, chronic CBG administration can provide at least 24 h of antinociceptive effect in mice. These findings support the study of CBG as a long-lasting neuropathic pain therapy, which acts without tolerance in both males and females.