A highly efficient directional molecular white-light emitter driven by a continuous-wave laser diode.
Tailored light sources have greatly advanced technological and scientific progress by optimizing the emission spectrum or color and the emission characteristics. We demonstrate an efficient spectrally broadband and highly directional warm-white-light emitter based on a nonlinear process driven by a cheap, low-power continuous-wave infrared laser diode. The nonlinear medium is a specially designed amorphous material composed of symmetry-free, diamondoid-like cluster molecules that are readily obtained from ubiquitous resources. The visible part of the spectrum resembles the color of a tungsten-halogen lamp at 2900 kelvin while retaining the superior beam divergence of the driving laser. This approach of functionalizing energy-efficient state-of-the-art semiconductor lasers enables a technology complementary to light-emitting diodes for replacing incandescent white-light emitters in high-brilliance applications.


Metabolic disorders of purine metabolism affecting the nervous system.
The purines are a group of molecules used by all cells for many vital biochemical processes including energy-requiring enzymatic reactions, cofactor-requiring reactions, synthesis of DNA or RNA, signaling pathways within and between cells, and other processes. Defects in some of the enzymes of purine metabolism are known to be associated with specific clinical disorders, and neurological problems may be a presenting sign or the predominant clinical problem for several of them. This chapter describes three disorders for which the clinical features and metabolic basis are well characterized. Deficiency of adenylosuccinate-lyase (ADSL) causes psychomotor retardation, epilepsy, and autistic features. Lesch-Nyhan disease is caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and is characterized by hyperuricemia, motor and cognitive disability, and self-injurious behavior. Deficiency of myoadenylate deaminase (mAMPD) is associated with myopathic features. In addition to these disorders, several other disorders are briefly summarized. These include defects of phosphoribosylpyrophosphate synthase, adenosine deaminase (ADA), purine nucleoside phosphorylase (PND), deoxyguanosine kinase (dGK), or IMP dehydrogenase (IMPDH). Each of these disorders provides an unusual window on the unique importance of purine metabolism for function of different parts of the nervous system.


Multidimensional fatigue during rehabilitation in persons with recently acquired spinal cord injury.
To examine the change in multidimensional fatigue in people with spinal cord injury during post-acute rehabilitation, and to compare these scores with those of healthy adults. Furthermore, to examine correlations between different dimensions of fatigue at discharge and demographics, injury-related variables and indices of psychological adjustment. Longitudinal cohort study. From 86 patients admitted for spinal cord injury rehabilitation, between June 2011 and January 2013, 78 met the inclusion criteria, and 70 (90%) agreed to participate. Self-reported questionnaires were completed at admission and in the week before discharge. Questionnaires used assessed demographics, injury-related variables, multidimensional fatigue, and psychological adjustment. At admission, fatigue scores were very high and decreased significantly during rehabilitation. At discharge, fatigue scores were still significantly higher than those of healthy adults. The fatigue total score at discharge was weakly associated with demographic variables and injury-related variables. Psychological adjustment variables explained the largest proportion of variance of the fatigue total score and each of the subscales. Fatigue is an important consequence in people with recently acquired spinal cord injury. Associations between fatigue and psychological adjustment suggest that psychological interventions might be useful to diminish fatigue.


Hotheaded: TRPV1 as mediator of hippocampal synaptic plasticity.
TRPV1 is a sensory transduction channel that mediates thermal nociception and some aspects of pathological pain. In this issue of Neuron, Gibson et al. report that TRPV1 also plays important roles in hippocampal synaptic plasticity, presenting a potential challenge for TRPV1-targeted therapeutics for the treatment of pain.


Differential proteome association study of freeze-thaw damage in ram sperm.
In this study proteomics analysis was performed to investigate damage caused to ram sperm by the freeze-thaw process. Sperm motility, viability, reactive oxygen species (ROS) and adenosine triphosphate (ATP) content were measured to evaluate sperm quality. Compared with fresh groups, motility, viability and ATP content were all lower in freeze-thawed sperm (P < 0.001), and ROS content was higher (P < 0.001). Moreover, 25 differential protein spots were detected in two-dimensional gels using PDQuest 8.0 software and the corresponding proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF-TOF MS) coupled with searching of the NCBI protein sequence database. Among these proteins, hexokinase1 (HXK1), the enzyme that catalyzes the first step of glycolysis in the sperm glycolytic pathway, is known to be associated with sperm motility. Casein kinase II subunit alpha (CSNK2A2), a serine/threonine-selective protein kinase, is associated with sperm apoptosis. We used immunoblotting and immunofluorescence to analyze the expression and localization of these two proteins. HXK1 and CSNK2A2 expression levels in fresh sperm were significantly higher than that in freeze-thawed sperm (P < 0.001). HXK1 and CSNK2A2 were detected in the main part of the sperm flagellum, and the immunofluorescence signal from these proteins was weakened in the freeze-thawed group. Decreased expression of HXK1 and CSNK2A2 may be associated with decreased sperm motility and viability following freeze-thawing.


Reflecting on Concepts Relevant to Contemplating the Relationships Between Glucose-Insulin Perturbations, Nutrition, and Aging.
Background: Medical professionals attribute a crucial role in the development of several age-related, chronic health maladies to glucose-insulin perturbations - particularly, discernible insulin resistance (IR). However, little information is available concerning the degree to which relatively minor changes in IR participate over time in overall aging population, e.g., when circulating glucose and/or insulin concentrations are consistently within the higher end of normally accepted ranges. Objective: Obtaining precise knowledge is important, because proper nutritional management has the distinct capability of ameliorating the consequences. Methods: Five key concepts are suggested to underpin current thinking as to the applicable mechanisms and these are (1) the practical use of fasting blood glucose (FBG) levels as an estimate of IR, (2) the potential role of even slightly aberrant insulin regulation over time in the aging process, (3) the implementation of "continuum of risks" rather than checkpoints in considering prevention, (4) the presence and meaning of an aging paradox discovered in a recent study, and (5) the importance nutritional considerations in the "deadly triangle" as key factors in aging. Conclusions: Maintaining relatively low levels of FBG representing IR during aging via nutritional means has the potential to deliver a longer, more healthful lifespan as well as ameliorate many adverse manifestations of aging.


Effect of pancreatic juice and trypsin on oleic acid-stimulated pancreatic secretion and plasma secretin in dogs.
We have investigated a negative feedback mechanism in the intestinal phase of pancreatic exocrine secretion in dogs with gastric cannulas and Thomas duodenal cannulas in whom pancreatic juice was collected by cannulation of the main pancreatic duct. Intraduodenal infusion of oleic acid emulsion in a dose of 18 mmol/h resulted in a significant increase in pancreatic secretion of water, bicarbonate, and protein, which was accompanied by increased plasma concentrations of both secretin and cholecystokinin. Infusion of pancreatic juice or bovine trypsin into the duodenum significantly inhibited the oleic acid-stimulated pancreatic secretion. This inhibition coincided with a significant decrease in plasma secretin level, whereas plasma cholecystokinin concentration was not affected by either pancreatic juice or trypsin. Neither pancreatic secretion nor plasma secretin concentration was affected by intraduodenal administration of NaHCO3 solution. The trypsin-induced suppression of pancreatic secretion was prevented by intravenous administration of secretin in a dose that achieved a plasma secretin level comparable to that during the oleic acid administration. This study indicates that a negative feedback mechanism is operative in the intestinal phase of pancreatic exocrine secretion in dogs, and endogenous secretin plays a significant role in the mechanism.


Self-Exfoliation of Flake Graphite for Bioinspired Compositing with Aramid Nanofiber toward Integration of Mechanical and Thermoconductive Properties.
A self-grinding exfoliation strategy that depends on mutual shear friction between flake graphite particles is successfully developed to prepare pristine graphene with largely enhanced yield and productivity. Bioinspired assembly of pristine graphene nanosheets to an interconnected aramid nanofiber network is achieved by a continuous sol-gel-film transformation strategy and generates a flexible yet highly thermoconductive film. Flexible yet highly thermoconductive materials are essential for the development of next-generation flexible electronic devices. Herein, we report a bioinspired nanostructured film with the integration of large ductility and high thermal conductivity based on self-exfoliated pristine graphene and three-dimensional aramid nanofiber network. A self-grinding strategy to directly exfoliate flake graphite into few-layer and few-defect pristine graphene is successfully developed through mutual shear friction between graphite particles, generating largely enhanced yield and productivity in comparison to normal liquid-based exfoliation strategies, such as ultrasonication, high-shear mixing and ball milling. Inspired by nacre, a new bioinspired layered structural design model containing three-dimensional nanofiber network is proposed and implemented with an interconnected aramid nanofiber network and high-loading graphene nanosheets by a developed continuous assembly strategy of sol-gel-film transformation. It is revealed that the bioinspired film not only exhibits nacre-like ductile deformation behavior by releasing the hidden length of curved aramid nanofibers, but also possesses good thermal transport ability by directionally conducting heat along pristine graphene nanosheets.


Triglyceride-poor very low density lipoprotein in human serum.
The chemical and physical properties of very low density lipoproteins, isolated from the pool of the sera of 60 persons with high pre-beta and normal triglyceride and cholesterol concentrations, have been studied. These very low density lipoproteins, a designated as triglyceride-poor very low density lipoproteins, consist of 20.5% phospholipids, 30.8% free cholesterol, 15% cholesterol esters and 33.7% triglycerides. Their protein content consists of 54.5% apo B, 26% apo A, 11.5% apo E and only 8% apo C, so they differ from any serum lipoprotein described until now. Triglyceride-poor very low density lipoproteins consist of spherical particles 300-450 A in diameter as revealed by electron microscopy.


Leishmania donovani serine protease encapsulated in liposome elicits protective immunity in experimental visceral leishmaniasis.
This study is aimed to evaluate the protective effect of L. donovani intracellular serine protease (SP-Ld) in combination with Freund's adjuvant and liposomal formulations against experimental visceral leishmaniasis (VL). The animals were immunized with SP-Ld in combination with adjuvant and evaluated for its immunogenicity and protective efficacy against Leishmania donovani. The infection was initially assessed by microscopic examination. Immunogenicity of SP-Ld was measured by detecting protease specific-IgG, IgG1 and IgG2a levels by ELISA. Cytokines levels were measured by ELISA and Reverse Transcription Polymerase Chain Reaction (RT-PCR). The vaccine efficacy of SP-Ld was also evaluated by measuring antibody response and survival potency in hamster model. SP-Ld vaccinated Balb/c mice resulted significant reduction of parasite burden with increased levels of IgG2a and decreased levels of IgG1. SP-Ld vaccination also induced Th1 type immune response with the rise of IL-12, IFN-γ and TNF-α with decreased levels of IL-10 and TGF-β. Importantly, liposomal incorporated SP-Ld exerted better protection rather than in combination with Freund's adjuvant. Additionally, liposome encapsulated SP-Ld vaccinated hamsters continued to survive beyond 8 months against virulent L. donovani post challenge. Overall, these findings demonstrated SP-Ld as an effective immunogen which opens a new perspective for the generation of potential vaccine candidate against leishmaniasis.


Aberrant trafficking of a proteolipid protein in a mild Pelizaeus-Merzbacher disease.
Pelizaeus-Merzbacher disease (PMD) is a rare X-linked leukodystrophy caused by proteolipid protein 1 (PLP1) gene mutations. Previous studies indicated that proteolipid proteins (PLPs) with disease-associated mutations are misfolded and trapped in the endoplasmic reticulum (ER) during transportation to the cell surface, which eventually leads to oligodendrocyte cell death in PMD. Here we report a PMD patient with a very mild phenotype carrying a novel mutation (485G-->T) in exon 4 of the PLP1 gene that causes a Trp(162)Leu substitution in the protein. We also investigated intracellular trafficking of this mutant PLP in COS-7 cells. Transiently transfected mutant PLP(W162L) fused to an enhanced green fluorescent protein (EGFP) or a short peptide tag was not carried to the plasma membrane. However, in contrast to previous studies, this mutant PLP was not retained in the ER, indicating an escape of the newly translated protein from the quality control machinery. We also found that the mutant PLP accumulated in the nuclear envelope (NE) in a time-dependent manner. This mutant PLP, with its distribution outside the ER and a very mild phenotype, supports the idea that accumulation of misfolded mutant protein in the ER causes the severe phenotype of PMD.


Malaria and associated co-morbidity in children admitted with fever manifestation in Western Ghana: A retrospective study.
Children under five years of age are highly vulnerable to malaria infection and often face dire consequences such as severe malaria if they are not promptly and adequately treated with effective anti-malarial medications. We set out to evaluate malaria and associated co-morbidity among children admitted with febrile illness in Sekondi-Takoradi, Ghana. This retrospective study focused on children admitted with fever over a three-year period at the pediatric unit of Effia-Nkwanta Regional Hospital. The children were identified, and the medical records of those who were successfully treated and discharged were searched, retrieved, and reviewed. A total of 1,193 children were identified and selected for analysis. The mean duration of admission increased from 2.17 days in 2010 to 3.36 in 2012. Conversely, the mean age decreased from 3.85 years in 2010 to 2.74 in 2012. Overall, laboratory-confirmed malaria prevalence decreased; however, this decrease was only observed among children five years of age or younger, while malaria prevalence increased among children one year of age or younger. The proportion of children with severe malarial anemia significantly increased, while the proportion of those with mild malaria decreased significantly. Despite the general decrease in malaria morbidity seen in this study, children younger than one year of age remain at increased risk of malaria morbidity. With an increase in malaria prevalence among children younger than one year of age over the three years of study, integrated and targeted control measures are highly needed for this age group.


Single-step purification and immobilization of MBP-phytase fusion on starch agar beads: application in dephytination of soy milk.
Periplasmic phytase, appA from E. coli has been noticed as a superior feed and food additive owing to its high specific activity, acidic pH optimum and resistance to gastric proteases. E. coli phytase was expressed as a fusion protein with maltose-binding protein, affinity-purified to homogeneity and, subsequently, immobilized in one step using a cost-effective matrix prepared from starch agar bead. Immobilized enzyme revealed an activity optimum at pH 6, while that of free enzyme was observed at pH 4. Both the immobilized and free enzyme showed a temperature optimum at 60 °C. Cleavage of 87 kDa fusion protein using factor Xa released 45 kDa appA. Hydrolysis of soy milk using immobilized enzyme led to 10% increase in release of inorganic phosphate at 50 °C relative to free fusion protein. This study suggests the usability of MBP as an immobilizing linker to other food enzymes for economical use in industry.


Body mass index and sleep in women aged 40 to 64 years.
A questionnaire study was carried out in 6000 randomly selected women in the County of Jämtland in Sweden. The response rate was 61.2%. Questions were asked about general health, height and body weight, sleep, menstruation and menopausal complaints. There were also questions about visits to doctors and the use of sleeping pills and hormone preparations. A deterioration of the night's sleep after the age of 60 years was associated especially with a low body mass index (BMI). In the subgroup with a BMI below 20 (kg m-2), frequent awakenings were reported 4 times more often in women 60-64 years old than in those aged 40-44 years. No such difference was found with a BMI > or = 30. In the age group 60-64 years twice as many women with BMI > or = 30 as women with BMI < 20 slept without waking up at night. BMI was similar in women with and without oestrogen therapy before the menopause. After the menopause the BMI in these two groups was 25.0 +/- 3.1 (mean +/- S.D.) and 25.6 +/- 3.8, respectively (P < 0.05). Oestrogen-treated women had fewer sleep disorders than other women of the same age. Of the premenopausal women, 3.4% used sleeping pills, compared with 8.0% after the menopause. Before the menopause the use of sleeping pills was not related to BMI, but after the menopause this use was twice as common among women with BMI < 20 kg m-2 than among those with BMI > or = 30kg m-2.


Optoacoustic model-based inversion using anisotropic adaptive total-variation regularization.
In optoacoustic tomography, image reconstruction is often performed with incomplete or noisy data, leading to reconstruction errors. Significant improvement in reconstruction accuracy may be achieved in such cases by using nonlinear regularization schemes, such as total-variation minimization and L 1-based sparsity-preserving schemes. In this paper, we introduce a new framework for optoacoustic image reconstruction based on adaptive anisotropic total-variation regularization, which is more capable of preserving complex boundaries than conventional total-variation regularization. The new scheme is demonstrated in numerical simulations on blood-vessel images as well as on experimental data and is shown to be more capable than the total-variation-L 1 scheme in enhancing image contrast.


Does weather anomaly still affect the emerging stock market under the unexpected event? New evidence from the COVID-19 pandemic.
This paper examines the impact of COVID-19 nationwide lockdown on the relationship between weather anomaly and the Vietnam stock market - a fast-growing emerging market. The paper employs event study methodology to compute the cumulative abnormal return of stocks during the pandemic, and the Holt-Winters Exponential Smoothing model to build the formula for weather anomaly for weather variables. In addition, a t-test is performed to examine the statistical significance of weather variables, as well as the impact that the lockdown order had on stock performance. Cross-sectional analysis by Ordinary Least Squares regression is also applied for estimating the relationship between weather and stock market performance. The finding shows that prior to the COVID-19 lockdown, all of the risk and return indicators, with the exception of idiosyncratic risk, are affected by temperature. After the lockdown order was withdrawn, temperature is only correlated with cumulative real returns and cumulative abnormal returns. Meanwhile, air pressure only appears to have an influence on cumulative abnormal returns after the lockdown, yet being the only meteorological factor that could impact the stock market during the lockdown. Generally, the larger the weather anomaly, the worse the returns and the higher the risks. The paper gives recommendations for listed companies and authorities to have better performance while engaging in and regulating the stock markets. Moreover, the results can be used as a reference for the investing community to incorporate meteorological factors into their analysis.


COVID-19 outcomes in persons with multiple sclerosis treated with rituximab.
Outcomes of COVID-19 in PwMS (persons with Multiple Sclerosis) on immunosuppressive therapies, particularly B-cell depletors, can be unpredictable. There has been a concern for postponing or avoiding use of Rituximab (RTX) during the COVID-19 pandemic. We report the course and outcomes of COVID-19 in PwMS receiving RTX. PwMS receiving RTX who contracted COVID-19 were closely monitored by tele-consultation and/or evaluated during hospital visits. Those requiring hospitalization for oxygen therapy or admission to ICU or expiring due to COVID-19 were considered to have severe disease. Those without desaturation and manageable at home were considered to have mild disease. Disease course and outcomes were noted. Twelve out of 62 (19.4%) PwMS on RTX therapy developed COVID-19. Four (age 35-49 years; mean 43.5) had severe COVID; three of whom had Secondary Progressive MS (SPMS). One PwMS expired. Two had prolonged fever lasting >1 month. One demonstrated features of SARS-CoV-2 reactivation. Interval from last RTX infusion (average dose 750 mg) to COVID-19 onset ranged 1-4 (mean 3.7) months. Eight PwMS had mild COVID-19 (age 26-54 years; mean 37.7); six had RRMS and two SPMS. RTX dose was lower (average dose 625 mg) and infusion to COVID-19 onset duration was longer, ranging 4-20 (mean 9.5) months. Four patients, two each from mild and severe COVID-19 groups had neurological deterioration, but none had true relapses. RTX treated PwMS may have unpredictable disease outcomes if they contract COVID-19, but may be at risk of severe disease and persistent infection. In our series higher age, SPMS, shorter interval from RTX infusion to COVID-19 onset and higher dose of RTX were noted amongst those developing severe disease. RTX should be use cautiously during the COVID-19 pandemic and if unavoidable, less frequent and lower doses should be considered. Patients receiving RTX must be counselled to follow strict COVID-19 preventive measures.


Effect of metal ions on lipopeptide secretion from Bacillus subtilis strain FJAT-4: Negative regulation by Ca2.
This study aimed to investigate the effect of metal ions on lipopeptide production by Bacillus subtilis strain FJAT-4 and the mechanism of negative regulation by Ca2+ . The quantitative measurement of lipopeptides in response to K+ , Na+ , Mg2+ and Ca2+ addition was carried out by LC-MS. The contents of fengycin and surfactin varied within the range of 116.24-129.80 mg/L and 34.03-63.11 mg/L in the culture media containing K+ , Na+ and Mg2+ , while the levels were 0.86 and 0.63 mg/L in the media containing Ca2+ . Ca2+ at a high concentration (45 mM) did not adversely affect the growth of strain FJAT-4, but caused significant downregulation of lipopeptide synthesis-related gene expression, corresponding to a decrease in lipopeptide production. This inhibition by Ca2+ was further investigated by proteomic analysis. In total, 112 proteins were upregulated and 524 proteins were downregulated in the presence of additional Ca2+ (45 mM). Among these differentially expressed proteins (DEPs), 28 were related to phosphotransferase activity, and 42 were related to kinase activity. The proteomics results suggested that altered levels of three two-component signal-transduction systems (ResD/ResE, PhoP/PhoR and DegU/DegS) might be involved in the control of expression of the fen and srfA operons of FJAT-4 under high calcium stress. The Ca2+ at the high concentration (45 mM) triggers a decrease in lipopeptide production, which might be attributed to the regulation of three two-component signal-transduction systems ResD/ResE, PhoP/PhoR and DegU/DegS. The regulatory effect of calcium on the expression of genes encoding lipopeptide synthetases can be applied to optimize the production of lipopeptides.


Substance P immunoreactivity released from rat spinal cord after kainic acid excitation of the ventral medulla oblongata: a correlation with increases in blood pressure.
Kainic acid injections into the ventral medulla oblongata of sodium pentobarbital-anesthetized rats caused an almost immediate increase in mean arterial pressure which reached hypertensive levels (greater than 200 mm Hg). Correlated with this rise in blood pressure was a two-fold increase in the amount of SP-like immunoreactivity (SPLI) in spinal cord superfusion samples. Baseline values obtained from a pool of two rats went from approximately 10 pg/10 min to approximately 20 pg/10 min. Rats pretreated with intracerebroventricular injections of the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), were also given kainic acid injections into the ventral medulla. 5,7-DHT did not block pressure response to kainic acid nor the elevation of SPLI in spinal cord superfusates. However, baseline levels of SPLI were decreased by approximately 50% in 5,7-DHT-treated rats. These findings show that activation of the ventral medulla oblongata causes an elevation of SPLI in spinal cord superfusates concomitant with an elevation in mean arterial blood pressure. These responses appear to be independent of serotonergic systems.


Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly.
Autosomal recessive primary microcephaly is a disorder of neurogenic mitosis that causes reduction in brain size. It is a rare heterogeneous condition with seven causative genes reported to date. Mutations in WD repeat protein 62 are associated with autosomal recessive primary microcephaly with cortical malformations. This study was initiated to screen WDR62 mutations in four consanguineous Pakistani families with autosomal recessive primary microcephaly. As part of a large study to detect the genetic basis of primary microcephaly in Pakistan, homozygosity mapping and DNA sequencing was used to explore the genetic basis of autosomal recessive primary microcephaly in four families. Four out of 100 families recruited in the study revealed linkage to the MCPH2 locus on chromosome 19, which harbor WDR62 gene. DNA sequencing in these MCPH2 linked families result in the identification of a novel nonsense mutation (p.Q648X) and three previously known mutations. Our data indicate that WDR62 mutations cause about 4% of autosomal recessive primary microcephaly in Pakistan.


Understanding the relationship between domestic and intimate partner violence, adverse childhood experiences, and chronic opioid use disorder: The patient perspective.
Opioid dependence and misuse are a plague of epidemic proportions in our communities and globally. Prior trauma in childhood may contribute to opioid dependence, while one consequence of opioid misuse is increased risk for involvement as both perpetrators and victims in domestic and intimate partner violence (DV and IPV). The aims of this study were to understand the proportion of patients who identified as having an opioid use disorder (OUD), if OUD was associated with higher rates of DV and IPV as both perpetrators and victims, and whether adverse childhood experiences (ACEs) as well as demographic factors related to instability in their social life were higher among those with OUD compared to those without. The sample consisted of 124 patients who were identified as having an OUD in their medical records based on ICD-10 codes. Each participant completed an anonymous survey about basic demographics, their alcohol, drug, and opioid intake, and their history of domestic and IPV. Descriptive statistics, univariate, and multivariate regression analyses were conducted in STATA 17.1 software. A sample of patients with an OUD diagnosis in their medical record found that 64 percent of patients acknowledged having a history of opioid addiction. Patients acknowledging OUD were more likely to not be married (divorced or single) (p < 0.01), younger than 50 years of age (p < 0.01), non-White (p < 0.01), and had higher average ACEs scores (p < 0.0X). Patients who reported OUD were also more likely to be both victims and perpetrators of DV/IPV compared to patients who denied OUD. OUD needs to be treated holistically to ensure that the adverse consequences of DV and IPV do not become a silent disease perpetuated on this population, their families, and society.


Rupture of an Occult Intracranial Mycotic Aneurysm after Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke.
The treatment of acute ischemic stroke with recombinant tissue plasminogen activator (rtPA) has become the mainstay of treatment, but its use carries a risk of subsequent intracranial hemorrhage (ICH). Guidelines have been developed to aid in the selection of the appropriate candidates to treat with rtPA to reduce this risk. We present a case of a stroke patient who was an appropriate candidate and was treated with rtPA who experienced a fatal subarachnoid hemorrhage due to a ruptured mycotic aneurysm (MA). A 51-year-old man presented to the Emergency Department with acute neurological symptoms concerning for acute ischemic stroke. His National Institutes of Health Stroke Scale score was 22. Emergent noncontrast head computed tomography (CT) revealed no sign of hemorrhage. The patient received intravenous rtPA, and about 1 h after the infusion was started, he had an acute deterioration in his mental status. Repeat CT scan revealed a large subarachnoid hemorrhage, and the patient was later found to have two intracranial aneurysms consistent with a ruptured MA that were related to his remote history of infective endocarditis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The majority of MAs are caused by infective endocarditis. In patients presenting with acute neurologic symptoms with a history of infective endocarditis, emergency physicians should strongly consider obtaining CT angiography to rule out MA prior to treating presumed acute ischemic stroke with rtPA.


Extreme adaptations in extreme and chronic circumstances: The application of "weaponized sex" to those exposed to ongoing incestuous abuse.
This paper examines Kluft's construct of "weaponized sex" through the prism of long-term clinical and research involvement with individuals subjected to ongoing sexual abuse during adulthood, a group that by definition has been exposed to more sexual abuse and for longer than any other defined victim population. Examples of the same sort of phenomena described by Kluft are repeatedly observed in therapy with members of this population, but usually not in a dramatic form. As might be anticipated, in order to survive, when an individual is closely attached to a long-term and extreme abuser, the sort of enduring ambivalence carried by the victim towards their primary abuser is manifested in compartmentalized states that wish their abuser dead, while other states in equally compartmentalized ways maintain the attachment via the use of sex-by continuing to be sexually involved with their primary abuser (usually their father), by fantasizing about sex with their abuser, by being sexually involved with those who co-abused with their father, or by staging reenactments with individuals whose sexual behavior re-evokes the abuse by the absent (or deceased) father. The process of healing means that inevitably some manifestations of the responses to such abuse spill over into therapy.


Determinants of all-cause in-hospital mortality among patients who presented with COVID-19 to a community teaching hospital in Michigan.
Race plays an important role in healthcare disparities, often resulting in worse health outcomes. It is unclear if other patient factors and race interactions may influence mortality in patients with COVID-19. We aimed to evaluate how multiple determinants of all-cause in-hospital mortality from COVID-19 were linked to race. A retrospective observational study was conducted at two hospitals in metropolitan Detroit. We identified patients aged ≥18 years-old who had tested positive for COVID-19 and were admitted between March 9 through May 16, 2020. Multivariable logistic regression was performed assessing predictors of all-cause in-hospital mortality in COVID-19. We identified 1064 unique patients; 74% were African Americans (AA). The all-cause in-hospital mortality was 21.7%, with the majority of deaths seen in AA (65.4%, P = 0.002) and patients 80 years or older (52%, P < 0.0001). AA women had lower all-cause mortality than AA men, white women, and white men based on race-gender interactions. In multivariable logistic regression analysis, older age (>80-year-old), dementia, and chronic kidney disease were associated with worse all-cause in-hospital mortality. Adjusted for race and body mass index (BMI), the main odds ratios (OR) and 95% confidence intervals (CI) are: Age 80 and older vs < 60 in females: OR = 7.4, 95% CI: 2.9, 18.7; in males OR = 7.3, 95% CI: 3.3, 16.2; Chronic Kidney Disease (CKD): OR = 1.7, 95% CI: 1.2, 2.6; Dementia: OR = 2.2, 95% CI: 1.5, 3.3. Gender significantly modified the association of race and COVID-19 mortality. African American females had the lowest all-cause in-hospital mortality risk compared to other gender-race groups.


The Modified Posterior Thoracotomy for Esophageal Atresia.
Right dorsolateral thoracotomy with splitting or sparing the latissimus dorsi is the standard approach to the esophageal atresia. The thoracoscopic approach to the treatment of esophageal atresia is a demanding procedure used only by few surgeons in few centers. The purpose of this study is to present the modified posterior thoracotomy for neonates with esophageal atresia. Between January 2007 and May 2016, the modified posterior thoracotomy was performed in 56 neonates with esophageal atresia. The modified posterior thoracotomy preserves the latissimus dorsi and the thoracodorsal nerve. Neither the latissimus dorsi nor the serratus anterior is mobilized or skin flaps elevated. Satisfactory exposure, functional, and cosmetic results were obtained. No complication related to the approach was encountered. The modified posterior thoracotomy is a reliable approach in the treatment of esophageal atresia in neonates.


The most influential papers in direct anterior approach to total hip arthroplasty.
Citation analysis is a commonly used method for appraising the impact of academic publications within a particular field of study. A gap exists in the citation analysis literature with regard to the topic of direct anterior approach (DAA) hip arthroplasty. The purpose of this study is to identify the 50 most frequently cited publications related to this topic. The Clarivate Analytics Web of Knowledge database was utilized to search for publications relating to DAA hip arthroplasty. The top 50 most cited articles that met inclusion criteria were recorded and reviewed for various metrics. The top 50 publications were cited a total of 3521 times, with an average of 86.3 total citations per year between 1980 and 2019. 47 of the 50 articles identified had been published since the year 2000. Cohort designs were the most common study type. This analysis provides insight into factors that characterize highly cited articles on the specific topic of DAA hip arthroplasty. These factors include higher levels of evidence, recent publication, and origin in the United States. Citations of DAA hip arthroplasty papers appear to be on the rise. The curation and analysis of this set of 50 articles will provide orthopaedic surgery clinicians, researchers, and residency program directors a guide for quickly isolating influential articles on the topic of DAA hip arthroplasty. This may serve as a quick reference for clinical decision-making, foundation for further research, and curriculum on DAA hip arthroplasty.


Evaluation of the Houston biochemical relapse definition in men treated with prolonged neoadjuvant and adjuvant androgen ablation and assessment of follow-up lead-time bias.
To validate the Houston prostate-specific antigen relapse definition in a mature cohort of men treated with external beam radiotherapy (EBRT) and adjuvant androgen ablation (AA) and men treated with EBRT monotherapy, and to compare these results with the American Society for Therapeutic Radiology and Oncology (ASTRO) and Vancouver prostate-specific antigen relapse (biochemical no evidence of disease) definitions. A prospective database of 1490 men treated with EBRT, with or without AA, was examined. The impact on hazard proportions, as well as the predictive ability, of the Houston, ASTRO, and Vancouver definitions was tested. For all patients, the Houston definition was more accurate (79.5%) than the ASTRO (76.7%) or Vancouver (77.2%) definitions in predicting subsequent clinical relapse. The Houston definition was superior to the ASTRO definition in those treated both with and without AA and equivalent to the Vancouver definition in those receiving AA. The Houston definition demonstrated proportional hazards when categorized for the use of AA, unlike the ASTRO and Vancouver definitions. The effect of inadequate follow-up on the projected relapse rates was negligible with the Houston definition. The Houston relapse definition is favored after EBRT monotherapy or combined EBRT and AA. Use of the Cox proportional hazard multivariate analysis is appropriate with the Houston definition, but not with the ASTRO or Vancouver definitions if AA and non-AA patients are combined.


Fibronectin-Expressing Mesenchymal Tumor Cells Promote Breast Cancer Metastasis.
Tumor metastasis is connected to epithelial-mesenchymal heterogeneity (EMH) and the extracellular matrix (ECM) within the tumor microenvironment. Mesenchymal-like fibronectin (FN) expressing tumor cells enhance metastasis within tumors that have EMH. However, the secondary tumors are primarily composed of the FN null population. Interestingly, during tumor cell dissemination, the invasive front has more mesenchymal-like characteristics, although the outgrowths of metastatic colonies consist of a more epithelial-like population of cells. We hypothesize that soluble FN provided by mesenchymal-like tumor cells plays a role in supporting the survival of the more epithelial-like tumor cells within the metastatic niche in a paracrine manner. Furthermore, due to a lower rate of proliferation, the mesenchymal-like tumor cells become a minority population within the metastatic niche. In this study, we utilized a multi-parametric cell-tracking algorithm and immunoblotting to evaluate the effect of EMH on the growth and invasion of an isogenic cell series within a 3D collagen network using a microfluidic platform. Using the MCF10A progression series, we demonstrated that co-culture with FN-expressing MCF10CA1h cells significantly enhanced the survival of the more epithelial MCF10CA1a cells, with a two-fold increase in the population after 5 days in co-culture, whereas the population of the MCF10CA1a cells began to decrease after 2.5 days when cultured alone (p < 0.001). However, co-culture did not significantly alter the rate of proliferation for the more mesenchymal MCF10CA1h cells. Epithelial tumor cells not only showed prolonged survival, but migrated significantly longer distances (350 µm compared with 150 µm, respectively, p < 0.01) and with greater velocity magnitude (4.5 µm/h compared with 2.1 µm/h, respectively, p < 0.001) under co-culture conditions and in response to exogenously administered FN. Genetic depletion of FN from the MCF10CA1h cells resulted in a loss of survival and migration capacity of the epithelial and mesenchymal populations. These data suggest that mesenchymal tumor cells may function to support the survival and outgrowth of more epithelial tumor cells within the metastatic niche and that inhibition of FN production may provide a valuable target for treating metastatic disease.


T-Cell Engagers in Solid Cancers-Current Landscape and Future Directions.
Monoclonal antibody treatment initially heralded an era of molecularly targeted therapy in oncology and is now widely applied in modulating anti-cancer immunity by targeting programmed cell receptors (PD-1, PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and, more recently, lymphocyte-activation gene 3 (LAG3). Chimeric antigen receptor T-cell therapy (CAR-T) recently proved to be a valid approach to inducing anti-cancer immunity by directly modifying the host's immune cells. However, such cell-based therapy requires extensive resources such as leukapheresis, ex vivo modification and expansion of cytotoxic T-cells and current Good Manufacturing Practice (cGMP) laboratories and presents significant logistical challenges. Bi-/trispecific antibody technology is a novel pharmaceutical approach to facilitate the engagement of effector immune cells to potentially multiple cancer epitopes, e.g., the recently approved blinatumomab. This opens the opportunity to develop 'off-the-shelf' anti-cancer agents that achieve similar and/or complementary anti-cancer effects as those of modified immune cell therapy. The majority of bi-/trispecific antibodies target the tumor-associated antigens (TAA) located on the extracellular surface of cancer cells. The extracellular antigens represent just a small percentage of known TAAs and are often associated with higher toxicities because some of them are expressed on normal cells (off-target toxicity). In contrast, the targeting of intracellular TAAs such as mutant RAS and TP53 may lead to fewer off-target toxicities while still achieving the desired antitumor efficacy (on-target toxicity). Here, we provide a comprehensive review on the emerging field of bi-/tri-specific T-cell engagers and potential therapeutic opportunities.


Degradation of 3-chlorobenzoate and phenol singly and in mixture by a mixed culture of two ortho-pathway-following Pseudomonas strains.
The compatibility and efficiency of two ortho-cleavage pathway-following pseudomonads viz. the 3-chlorobenzoate (3-CBA)-degrader, Pseudomonas aeruginosa 3mT (3mT) and the phenol-degrader, P. stutzeri SPC-2 (SPC-2) in a mixed culture for the degradation of these substrates singly and simultaneously in mixtures was studied. Another phenol-degrading strain, Pseudomonas sp. SoPC-5 (SoPC-5) that utilizes a meta-cleavage mode also was tried in co-culture with 3mT. The former combination was found to be a better degrader of both the substrates when present alone. But, with inoculum levels of 0.15 mg cell dry wt each of 3mT/SPC-2 or 3mT/SoPC-5 growth with 2 mM each of 3-CBA and phenol was slow with a lag of 24 h and degradation being incomplete. However, with higher inocula in the ratios 1:1, 1:2, and 2:1, i.e., 0.3 + 0.3, 0.3 + 0.6, and 0.6 + 0.3 mg cell dry wt of 3mT and SPC-2, respectively complete degradation of both the substrates occurred. Degradation of 3-CBA was complete with the release of stoichiometric amounts of chloride (Cl(-)) when concentrations of phenol/3-CBA were varied as 2:2, 2:4, and 4:2 mM, i.e., even when the concentration of the more toxic co-substrate 3-CBA was higher than phenol effective simultaneous degradation occurred at the inoculums ratio of 1:1 (0.3 mg dry cell wt. of each strain). These studies clearly indicated the better suitability of ortho-cleavage-utilizing strains as partners in a mixed culture than those follow different modes.


Super-Resolution Imaging of Highly Curved Membrane Structures in Giant Vesicles Encapsulating Molecular Condensates.
Molecular crowding is an inherent feature of cell interiors. Synthetic cells as provided by giant unilamellar vesicles (GUVs) encapsulating macromolecules (poly(ethylene glycol) and dextran) represent an excellent mimetic system to study membrane transformations associated with molecular crowding and protein condensation. Similarly to cells, such GUVs exhibit highly curved structures like nanotubes. Upon liquid-liquid phase separation their membrane deforms into apparent kinks at the contact line of the interface between the two aqueous phases. These structures, nanotubes, and kinks, have dimensions below optical resolution. Here, these are studied with super-resolution stimulated emission depletion (STED) microscopy facilitated by immobilization in a microfluidic device. The cylindrical nature of the nanotubes based on the superior resolution of STED and automated data analysis is demonstrated. The deduced membrane spontaneous curvature is in excellent agreement with theoretical predictions. Furthermore, the membrane kink-like structure is resolved as a smoothly curved membrane demonstrating the existence of the intrinsic contact angle, which describes the wettability contrast of the encapsulated phases to the membrane. Resolving these highly curved membrane structures with STED imaging provides important insights in the membrane properties and interactions underlying cellular activities.


CIP2A and TOPBP1: Molecular lassos that herd pulverized micronuclear chromosomes.
Lin et al.1 demonstrate that acentric chromosome fragments generated within micronuclei are tethered by the CIP2A-TOPBP1 complex during mitosis, thus promoting clustered segregation of the fragments to a single daughter cell nucleus and facilitating re-ligation with limited chromosomal scattering and loss.


Construction of broad-host-range plasmid vectors for easy visible selection and analysis of promoters.
We have constructed a series of broad-host-range plasmids which use "visual screens" to detect promoter activity. These plasmids contain the pMB1 and pRO1600 origins of replication and are capable of replicating in a wide range of gram-negative bacteria. The genes encoding beta-galactosidase and alkaline phosphatase from Escherichia coli and bacterial luciferase from Vibrio harveyi supply the promoterless indicator genes. The constructs were tested in E. coli and Pseudomonas aeruginosa.


Allometric growth in three species of digenetic trematodes of marine fishes from Belize.
Allometric growth of body proportions and organs is determined for three speciies of digenetic trematodes of marine fishes from Belize: Apocreadium mexicanum Manter, 1937 (Apocreadiidae), Pseudocreadium lamelliforme (Linton. 1907) Manter, 1946 (Lepocreadiidae), Paracryptogonimus americanus Manter, 1940 (Cryptogonimidae). These are compared with three other species in which allometric growth has been studied. In all species only the hindbody shows positive growth, whereas the forebody, suckers, and pharynx are consistently negative. The body width, posttesticular body, testes, and ovary are positive in some species and negative in others. In some instances the body proportion or organ is growing at the same rate as the body length.


Clinical and genetic update of hereditary spastic paraparesis.
Hereditary spastic paraparesis is a group of inherited neurological diseases characterized by underlying wide genetic heterogeneity. It should be suspected if there is a positive familial history, a common genetic alteration (i.e. SPG4, the most overall frequent form), or association with other signs, such as cerebellar ataxia (i.e. SPG7), early cognitive impairment or even cognitive deficit (i.e. SPG11), or peripheral neuropathy (i.e. SACS). The natural history is known for certain genetic subgroups, with genotype-phenotype correlations partially explaining childhood or late onset. However, the search for genetic modifying factors, in addition to the causal pathogenic variant or environmental influencers, is still needed. Novel approaches to provide etiological treatment are in the pipeline for SPG11. Symptomatic treatments are available but would benefit from randomized controlled trials.


Epstein-Barr virus serology and isoelectrofocusing pattern of serum immunoglobulins in cyclosporin or placebo-treated type I diabetics.
Epstein-Barr virus (EBV) serology was serially studied for a period of 18 months in 49 recently diagnosed type I diabetics randomly assigned to receive cyclosporin (CsA) (n = 25) or placebo (n = 24). Additionally, isoelectrofocusing of serum (IEF) was serially performed in 59 CsA- and 38 placebo-treated diabetics, over a 36 month period (687 sera) in order to detect restriction of heterogeneity of circulating immunoglobulins. Patients were continuously treated with CsA at a dose of 7.5-10 mg/day during the first 6 months and a dose not exceeding 5 mg/kg/day, thereafter. Before treatment anti-EBV antibody levels were in the normal range for the whole group. In the placebo group, Epstein-Barr nuclear antigen (EBNA) and viral capsid antigens (VCA) IgG were moderately raised during the first 6 months in comparison with baseline level (0.33 +/- 0.13 and 0.30 +/- 0.18 two-fold dilutions respectively). In contrast, in the CsA group, EBNA and VCA IgG decreased slightly (0.26 +/- 0.16 and 0.26 +/- 0.17 dilutions). Changes between the two groups at 3 and 6 months were significantly different (P less than 0.05), but the difference disappeared subsequently. No significant changes in anti-early antigen (EA) IgG and in EA and VCA IgA were observed. No IEF abnormalities appeared in the CsA group. One CsA-treated patient who was initially EBV seronegative developed normal serological signs of recent EBV infection at 12 months without restriction of immunoglobulin heterogeneity or clinical symptoms of infectious mononucleosis. This study indicates that CsA, at moderate dosage, slightly reduces the titer of pre-existing anti-EBV antibodies but does not alter the response to recent EBV infection. These results do not provide any evidence of clinically latent EBV-induced benign or malignant lymphocyte proliferation.


Transcription of CYP19A1 is directly regulated by SF-1 in the theca cells of ovary follicles in chicken.
Many studies have suggested the important role of estrogen in ovarian differentiation and development of vertebrates including chicken. Cytochrome P450 aromatase, encoded by CYP19A1, is a key enzyme in estrogen synthesis, but the mechanism of CYP19A1 regulation in chicken remains unknown. Here, we found that CYP19A1 was only expressed in the theca cell layers of chicken ovary follicles. Steroidogenic factor 1 (SF-1, also named as nuclear receptor subfamily 5 group A member 1, NR5A1), a potential regulators, was expressed in both the theca cell layers and granulosa cell layers. Forkheadbox L2 (FOXL2), another potential regulator, was only expressed in the granulosa cell layers. Using luciferase assays in vitro, we found that SF-1 could activate the promoter of CYP19A1 by binding to the nuclear receptor half-site (5'-TCAAGGTCA-3') from -280 to -271 base pairs. FOXL2 did not activate the promoter of chicken CYP19A1 gene in either 293T or DF-1 cells. Overexpression of SF-1 in DF-1 cells upregulated aromatase expression, but FOXL2 could not. Taken together, our results indicated that SF-1 activates CYP19A1 mRNA expression via a conserved binding site in chicken ovary, but FOXL2 may not affect the expression of CYP19A1.


Morphological polarizations of sensory hair cells in the three otolithic organs of a teleost fish: fluorescent imaging of ciliary bundles.
It has been suggested that the morphological polarity of sensory hair cells in the otolithic organs plays important roles in directional hearing in fish. In this study, we examined the hair cell polarization patterns in the saccule, utricle, and lagena of a teleost fish, the sleeper goby (Dormitator latifrons). In contrast to using traditional scanning electron microscopy, we employed a simple and rapid method that enabled us to map the hair cell polarization patterns using immunocytochemical and confocal imaging techniques. The hair cells in the caudal part of the saccular epithelium are oriented dorsally and ventrally, with some variations in the caudal end. The hair cells in the rostral part have diverse morphological polarizations. The utricular hair cells fall into internal and external groups which have opposing polarizations. The lagenar hair cells are found in anterior and posterior groups with approximately opposite polarizations. The saccular and lagenar epithelia are oriented perpendicular to the horizontal plane of the fish, while the utricular epithelium lies on the horizontal plane. Thus, the sleeper goby's ear is morphologically capable of being a three-dimensional sound detector.


Midterm outcome of off-pump bypass procedures versus drug-eluting stent for unprotected left main coronary artery disease.
Although surgical revascularization is recommended for the treatment of left main coronary artery (LMCA) disease, percutaneous coronary intervention (PCI) attempts have increased, especially after the introduction of the drug-eluting stent. The goal of this study was to compare the midterm outcomes between drug-eluting stenting and off-pump coronary artery bypass (OPCAB) grafting in LMCA disease. Five hundred twelve consecutive patients with unprotected LMCA disease who underwent OPCAB (N = 269) or drug-eluting stenting (N = 243) were enrolled. We compared major cardiac and cerebrovascular events (MACCEs) in a real-world cohort and in a matching patient cohort (N = 256). The duration of mean follow-up was 38 ± 20 months, and the follow-up rate was 97.7%. In a real-world comparison, the OPCAB group showed better 5-year freedom from MACCEs compared with the stenting group (71.5% ± 4.4% versus 67.6% ± 4.0%; p = 0.031), despite worse patient characteristics. After patient matching, the OPCAB group showed more distinct benefit in 5-year freedom from MACCEs (75.3% ± 6.6% versus 62.8% ± 5.4; p < 0.001), including a significantly lower target vessel revascularization (TVR) rate (p < 0.001). In a subgroup analysis, the benefit of OPCAB regarding 5-year freedom from MACCEs was more clearly defined for lesions of the distal LCMA and in LMCA lesions with multivessel disease (p = 0.015, p = 0.004, respectively). Patients with LMCA disease who were treated with OPCAB showed better 5-year freedom from MACCEs in a real-world practice and in a patient matching cohort compared with the drug-eluting stenting group. TVR was the main factor that made the difference. The benefit of OPCAB was more prominent in distal LMCA lesions and in LMCA lesions with multivessel involvement.


Associations between inflammatory cytokines and organ damage in pediatric patients with hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease characterized by overwhelming inflammation response and multiple organ damage. Most of the clinical and laboratory manifestations of HLH are thought to be related to hypercytokinemia and organ infiltration with lymphocytes and histiocytes. The aim of this study was to investigate the associations between cytokines and various manifestations of HLH. A total of 105 patients diagnosed with HLH were enrolled in this retrospective study. The information including the patients' demographic characteristics, clinical and laboratory findings at presentation and cytokine data were collected. The median age at diagnosis was 2.8years, with 74 patients (70.4%) documented Epstein-Barr virus infection. Hepatomegaly (88.6%), splenomegaly (81.9%), cytopenia (68.6%), elevated ferritin level (93.3%), hypofibrinogenemia (61.9%) and hemophagocytosis (77.3%) were found in more than half of the patients. Interleukin (IL)-6, IL-10 and interferon (IFN)-γ were found to be moderately or significantly elevated in most patients. In the correlation analysis, IFN-γ was closely related to the concentration of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, lactate dehydrase (LDH), triglyceride and fibrinogen, while IL-10 was associated with platelet count. When split the patients into two groups according to the cytokine levels, patients with high IFN-γ presented higher level of ALT, AST, bilirubin, LDH, triglyceride, and fibrinogen, while patients with high IL-10 presented much lower hemoglobin and platelet count. In conclusion, the present study put forward clinical evidence that hypercytokinemia is related to organ damage in HLH. IFN-γ may contribute to liver impairment and coagulation disease, while IL-10 is a cytokine related to cytopenias.


Development of monoclonal antibodies and ELISA specific for the mouse vascular endocan.
Human vascular endocan is a proteoglycan exhibiting tumorigenic activity through both its glycan and protein cores. Endocan mRNA is identified as being one of the most significant molecular signatures defining a poor prognosis in lung, breast, kidney, prostate, and thyroid malignancies. The survival inversely correlates with endocan expression in tumor tissue from hepatocarcinoma, and in serum from lung cancer. In mouse, endocan mRNA is also increased in tumor vessels. However, mouse endocan has not yet been fully characterized. Here, we produced a panel of rat monoclonal antibodies directed against mouse endocan, leading to the development of a specific mouse/rat endocan ELISA. Mouse endocan serum level was measured at a median of 0.96 ng/mL and 1.08 ng/mL in 129Sv mice and C57bl6, respectively. These results also provide new tools to characterize and explore the role of endocan in mouse and rat models of human diseases. These results present mouse vascular endocan as a circulating molecule similar to human endocan.


Long-term Outcomes of Adolescent Anorexia Nervosa on Bone.
Anorexia nervosa (AN) is a chronic and life-threatening eating disorder that can have a considerable negative impact on the growing skeleton. We hypothesized that the long-term impact on bone health may persist even after normalization of body weight. 41 females (mean age 21.2 ± 2.9 years) with a history of adolescent-onset AN attended a follow-up bone health assessment at 5 years (T5, n = 28) or 10 years (T10, n = 13) after their first AN-related hospital admission. Assessment included dual-energy x-ray absorptiometry measurements of the total body, lumbar spine, and proximal femur, peripheral quantitative computed tomography at the radius and tibia, anthropometric measurements, serum biochemistry, fracture history, and a patient questionnaire. A recovery in body weight and BMI was seen for both the T5 and T10 cohorts (BMI at intake 16.6, BMI at T5-T10 21.2-21.3). Dual-energy x-ray absorptiometry body composition indicated a recovery of fat mass and lean tissue mass. Total BMD was unaffected, but reductions were seen at the femoral neck and arms. Peripheral quantitative computed tomography showed reduced trabecular and cortical bone in the radius, and cortical thinning in the tibia. AN patients showed a statistically significant reduction in measures of radiographic bone health at follow up, although not to a degree that necessitated clinical intervention. Serum insulin-like growth factor 1 was also positively correlated with total BMD and BMC measures. While fracture risk was not increased, a subset of participants (8%) showed multiple (>4) fractures. A longitudinal study of adolescent AN showed persisting negative effects on bone health.


Soil erodibility indices under different land uses in Ri-Bhoi district of Meghalaya (India).
In absence of soil erosion plots for determination of erodibility index (K) for erosion models like Universal Soil Loss Equation (USLE) or Revised Universal Soil Loss Equation (RUSLE) to estimate soil erosion, empirical relations are used. In the present study, soil erodibility index was determined for entire Ri-bhoi district of Meghalaya based on soil physical and chemical properties through empirical relationship and presented in a map form. Dominant land uses of the district were identified through geo-spatial tools which were viz. agriculture, forest, jhum land and wasteland. Soil samples from surface depth (01-15 cm) were collected from areas of different dominant land uses. Twenty five sampling points were selected under each land use type and geo-coded them on the base map of Ri-bhoi district. Apart from K-index, Clay Ratio, Modified Clay Ratio and Critical Soil Organic Matter were also determined for understanding the effect of primary soil particles on erodibility. In agriculture land use system K-index values were found in the range of 0.08-0.41 with an average of 0.25 ± 0.02. In case of jhum, forest and wasteland these were in the range of 0.08-0.42 with an average of 0.20 ± 0.01; 0.09-0.40 with an average of 0.22 ± 0.02, and 0.10-0.34 with an average value of 0.23 ± 0.02, respectively. Clay ratio (2.74) and Modified clay ratio (2.41) were observed to be higher in forest LUS, lower clay ratio (1.97) and modified clay ratio (1.81) were found in the wasteland indicating erosion susceptibility in forested area. The values of Critical Level of Organic Matter (CLOM) for the district ranged from 4.72 to 16.56. Out of 100 samples, only one sample had CLOM value less than 5 and rest 99 samples had values more than 5 indicating that the soils of the district had moderate to stable soil structure and offer resistance to erosion. All the indices values of geo-coded points were then interpolated in the Arc-GIS environment to produce land use based maps for Ri-bhoi district of Meghalaya. As K-index is a quantitative parameter which is used in models, the index can be then interpolated for estimation of soil erosion through USLE or RUSLE for any given situation.


Effects of stimulus frequency and age on bidirectional synaptic plasticity in the dentate gyrus of freely moving rats.
We investigated the frequency-dependent transition from homosynaptic long-term depression (LTD) to long-term potentiation (LTP) at the lateral perforant pathway/dentate gyrus synapse in adult (90 days of age) and immature (15 days of age) awake, freely moving rats. Dentate-evoked field potentials were recorded and analyzed using the population spike amplitude and the field EPSP slope measures following sustained stimulation (900 pulses) of the lateral perforant pathway at various frequencies (1, 3, 7, 30, 50, or 200 Hz). Our results indicate that both the strength and the direction (LTP or LTD) of synaptic plasticity vary as a function of activation frequency: sustained low-frequency stimulation ranging from 1 to 7 Hz results in depression of activated synapses, whereas high-frequency stimulation (30-200 Hz) produces potentiation. In addition, a significant (P < 0.01) ontogenetic shift in the frequency of transition from LTD to LTP was observed; the transition frequency in immature animals was significantly lower than that obtained in adult animals. These observations agree strongly with the prediction of the Bienenstock-Cooper-Munro theory of synapse modification, indicating perhaps a neurophysiological basis for this theoretical model of learning in the dentate gyrus of awake behaving rats.


Xenopus Germes encodes a novel germ plasm-associated transcript.
A cDNA tag specific for the vegetal pole of early Xenopus embryo was used to isolate a novel cDNA using RACE technique. The corresponding mRNA demonstrated a localization pattern typical for the germ plasm-associated messages, and was, therefore, named Germes. The open reading frame of Germes encodes a predicted 68 kDa protein with two leucine zipper motifs and a putative EF-hand domain, but otherwise no substantial homology to known proteins. In situ hybridization analysis shows that Germes transcript localizes to the vegetal cortex via the mitochondrial cloud early in oogenesis and segregates with the germ plasm during early embryogenesis. Our data indicate that Germes is a novel germ plasm-specific RNA.


Limiting laws and counterion condensation in polyelectrolyte solutions. V. Further development of the chemical model.
Counterion binding to polyelectrolyte chains is formulated as a chemical reaction Mz (free) leads to Mz (bound). Expressions for the chemical potentials of free and bound counterions are set equal to obtain the reaction equilibrium. The results are equivalent to those in the previous paper of this series. An additional result obtained here is that a polyion holds its bound counterion layer with a strength on the order of 100 kcal/(mole cooperative unit). The method is then applied to the calculation of the polarizability along the chain due to the bound (condensed) counterions.


Can a community health worker administered postnatal checklist increase health-seeking behaviors and knowledge?: evidence from a randomized trial with a private maternity facility in Kiambu County, Kenya.
Since the 2009 WHO and UNICEF recommendation that women receive home-based postnatal care within the first three days after birth, a growing number of low-income countries have explored integrating postnatal home visit interventions into their maternal and newborn health strategies. This randomized trial evaluates a pilot program in which community health workers (CHWs) visit or call new mothers three days after delivery in peri-urban Kiambu County, Kenya. Participants were individually randomized to one of three groups: 1) early postnatal care three days after delivery provided in-person with a CHW using a simple checklist, 2) care provided by phone with a CHW using the same checklist, or 3) a standard of care group. Surveys were conducted ten days and nine weeks postnatal to measure outcomes related to compliance with referrals, self-reported health problems for mother and baby, care-seeking behaviors, and postnatal knowledge and practices around the recognition of danger signs, feeding, nutrition, infant care and family planning. The home visit administration of the checklist increased the likelihood that women recognized postnatal problems for themselves and their babies and increased the likelihood that they sought care to address those problems identified for the child. In both the home visit and mobile phone implementation of the checklist, actions taken for postnatal problems happened earlier, particularly for infants. Knowledge was found to be high across all groups, with limited evidence that the checklist impacted knowledge and postnatal practices around the recognition of danger signs, feeding, nutrition, infant care and family planning. We find evidence that CHW-administered postnatal checklists can lead to better recognition of postnatal problems and more timely care-seeking. Furthermore, our results suggest that CHWs can affordably deliver many of the benefits of postnatal checklists. ClinicalTrials.gov NCT02104635 ; registered April 2, 2014.


Accurately measured and properly heart-rate corrected QTc intervals show little daytime variability.
Circadian QTc changes have been reported, with conflicting results. Spontaneous QTc variability is important for pharmaceutical cardiac safety studies. The purpose of this study was to investigate QTc variability in accurately measured and heart-rate corrected daytime data of healthy subjects. Continuous 12-lead ECGs were recorded in 53 healthy volunteers. For each recording, approximately 320 ECG samples of 10 seconds were obtained throughout the daytime period, all preceded by stable heart rates. In each ECG sample, QT interval was measured on superimposed 12 leads by two independent cardiologists and reconciled. Four RR-interval expressions were used: (a) average of the first three RR of the ECG sample, (b) RR average of the 10-second sample, (c) average of RR intervals in a 2-minute history, and (d) RR intervals of an independently established individual QT/RR hysteresis profile. For all RR-interval expressions, QT intervals were corrected using the Fridericia formula and individually optimized curvature correction. QTc variability was measured by intraindividual QTc standard deviations. With Fridericia correction and the RR expressions (a) to (d), QTc variability obtained was (a) 9.45 +/- 1.70 ms, (b) 7.80 +/- 1.48 ms, (c) 6.37 +/- 1.64 ms, and (d) 5.81 +/- 1.75 ms. With individualized correction, QTc variability was (a) 8.16 +/- 1.71 ms, (b) 6.71 +/- 1.41 ms, (c) 5.22 +/- 1.13 ms, and (d) 4.56 +/- 1.18 ms. All differences (b) vs (a), (c) vs (b), and (d) vs (c) were highly statistically significant (P <10(-12) in all cases). Previously reported large QTc variability largely results from methodologic imprecision. Little QTc variability is present in daytime recordings of healthy subjects. Consequently, QT-related pharmaceutical cardiac safety studies can be made smaller without decreasing their power.


Living With an Advanced Cancer While Parenting Minor Children: A Needs Assessment Study.
Evidence-based interventions addressing the needs of couples co-parenting young children while facing an advanced cancer diagnosis are lacking. Thus, this study seeks to identify parenting-related intervention needs and delivery preferences of advanced cancer patients and their spouses/co-parents. Twenty-one couples completed quantitative measures of cancer-related parenting concerns, relationship and family functioning, and service needs along with individual semi-structured interviews. Patients (mean age=44 years, 48% female, 91% White) and spouses (mean age=45 years, 52% female, 91% White) reported family distress (62% of couples) and marital distress (29% of couples). Parenting concerns were generally high with patients revealing concerns particularly regarding the practical impact of the cancer on the child(ren). Spouses rated concerns about the co-parent significantly higher (P<.001) than patients. Parenting concerns were inversely associated with relationship (P<.001 for patients; P=.03 for spouses) and family functioning (P<.001 for patients). Themes identified through qualitative interviews include needs related to maintenance of family routines and traditions, childcare, transportation, meals, home maintenance, and finances. Couples who endorsed marital distress also indicated a need for conflict resolution skills. All patients and 89% of spouses would like to receive parenting-related education/services; up to 50% of couples preferred targeted, self-led readings without therapist support; and up to 50% desired counseling sessions indicating a preference towards dyadic and video conferenced intervention delivery. The delivery of optimal supportive care involves a family-focused perspective such as screening for parenting status and referrals to social work services to address the need of tangible resources and manage parenting-related distress.


The Rosenblueth phenomenon.
Rosenblueth and Luco demonstrated in 1939 that, during prolonged stimulation of a motor nerve, neuromuscular fatigue is followed by a rise of tension that has been called the Rosenblueth Phenomenon. The purpose of this work was to investigate the Rosenblueth Phenomenon in a cat neuromuscular preparation in which the nerves were severed at different levels and stimulated at 60 Hz for several hours. It was demonstrated that in the longer nerve preparation the Rosenblueth Phenomenon starts earlier and its maximal tension is higher. Acetylcholine sensitivity was studied in the superior cervical ganglion preparation and no change was observed when tested before stimulation, during fatigue, and during the Rosenblueth Phenomenon. It is concluded that the onset and amplitude of the Rosenblueth Phenomenon depend on the length of the peripheral nerve stump: the longer the stump, the earlier and higher the response. It is suggested that the Rosenblueth Phenomenon is produced by an increase in the transmitter release which would be due to axonal progression of molecules along the nerve.


Comparative transcriptomics provide new insights into the mechanisms by which foliar silicon alleviates the effects of cadmium exposure in rice.
Silicon (Si) has been shown to alleviate Cd stress in rice. Here, we investigated the beneficial effects of foliar Si in an indica rice Huanghuazhan (HHZ). Our results showed that foliar Si increases the dry weight and decreases Cd translocation in Cd-exposed rice at the grain-filling stage only, implying that the filling stage is critical for foliar Si to reduce Cd accumulation. We also investigated the transcriptomics in flag leaves (FLs), spikelets (SPs), and node Is (NIs) of Cd-exposed HHZ after foliar Si application at the filling stage. Importantly, the gene expression profiles associated with the Si-mediated alleviation of Cd stress were tissue specific, while shared pathways were mediated by Si in Cd-exposed rice tissues. Furthermore, after the Si treatment of Cd-exposed rice, the ATP-binding cassette (ABC)-transporters were mostly upregulated in FL and SP, while the bivalent cation transporters were mostly downregulated in FL and NI, possibly helping to reduce Cd accumulation. The genes associated with essential nutrient transporters, carbohydrate and secondary metabolite biosynthesis, and cytochrome oxidase activity were mostly upregulated in Cd-exposed FL and SP, which may help to alleviate oxidative stress and improve plant growth under Cd exposure. Interestingly, genes responsible for signal transduction were negatively regulated in FL, but positively regulated in SP, by foliar Si. Our results provide transcriptomic evidence that foliar Si plays an active role in alleviating the effects of Cd exposure in rice. In particular, foliar Si may alter the expression pattern of genes associated with transport, biosynthesis and metabolism, and oxidation reduction.


Binge drinking in Japan during the COVID-19 pandemic: Prevalence, correlates and association with preventive behaviors.
There is some evidence that alcohol use may have changed during the coronavirus pandemic. However, as yet, there has been comparatively little focus on heavy/excessive drinking. This study examined binge drinking (BD) in Japan during the coronavirus pandemic and its association with COVID-19 preventive behaviors. Data were analyzed from an online sample of 1452 individuals aged 18 and above that were collected one year after the beginning of the pandemic. Self-reported information was obtained on current and pre-pandemic BD and a range of sociodemographic and health-related variables. Logistic regression analysis was used to examine associations. Just under one-third of the sample (29.3%) reported past-month BD. More individuals reduced rather than increased BD during the pandemic (11.5% > 6.5%). Worsening household finances and depressive symptoms were associated with both current and increased BD, while young age (18-29) was linked to both increased and decreased BD. Individuals who binged had significantly lower odds for engaging in several COVID-19 preventive behaviors including wearing a mask (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.30-0.76), hand washing (OR: 0.58, 95%CI: 0.44-0.76) and avoiding crowds/staying at home (OR: 0.72, 95%CI: 0.55-0.93). BD is prevalent in Japan during the coronavirus pandemic and associated with poorer adherence to COVID-19 preventive behaviors. Increasing public awareness of the potentially detrimental effects of heavy alcohol use during the ongoing pandemic is now a public health priority.


Evaluation of the Hunter-Sessions self-retaining aortic cannula.
A report of our experience with a new self-retaining aortic cannula is presented. We have used this cannula in more than 30 patients and found it to be very secure and convenient for rapid cannulation since no pursestring sutures are required for initial placement.


Ecological studies of Eastern Australian fruit flies (Diptera: Tephritidae) in their endemic habitat : I. Temporal variation in abundance.
Fortnightly fruit fly captures for a 2-year period at Cooloola (south-east Queensland) contained 11 species. Three species, viz., D. tryoni, D. neohumeralis and D. endiandrae predominated. The peak trap catches of 7 species corresponded with the peak fruiting times of their major hosts. There was no direct relationship between temperature and rainfall and the variations in population numbers. The host plants of some species do not grow in the Cooloola area and there is evidence that large numbers of flies migrate into the region from other breeding areas up to 100 km away. Pockets of tropical rainforest such as Cooloola could be important adult fruit fly feeding areas even in the absence of larval host plants.


H3 and H4 histone cDNA sequences from Xenopus: a sequence comparison of H4 genes.
Ovarian poly (A) + RNA from Xenopus laevis and Xenopus borealis was used to construct two cDNA libraries which were screened for histone sequences. cDNA clones to H4 mRNA were obtained from both species and an H3 cDNA clone from Xenopus laevis. The complete DNA sequences of these clones have been determined and are presented. These new sequences are compared with other H3 and H4 DNA sequences both in the coding and 3' noncoding regions. We find that there is considerable non-random codon usage in ten H4 genes. In addition there are some sequence similarities in the 3' noncoding regions of H3 and H4 genes.


Potential miRNA biomarkers for the diagnosis and prognosis of esophageal cancer detected by a novel absolute quantitative RT-qPCR method.
miRNAs are expected to become potential biomarkers in the diagnosis and prognosis of Esophageal cancer (EC). Through a series of screening, miR-34a-5p, miR-148a-3p and miR-181a-5p were selected as EC-associated miRNAs. Based on AllGlo probe, a novel absolute quantitative RT-qPCR method with high sensitivity, specificity and accuracy was established for detecting miRNAs. Then the clinical significance of these 3 miRNAs was explored with 213 patients (166 cases with EC and 47 cases with benign diseases) and 170 normal controls. Compared with normal controls, the level of miR-34a-5p increased while miR-148a-3p and miR-181a-5p decreased in EC and benign patients (P < 0.001), and the level of miR-181a-5p in early EC patients was significantly lower (P < 0.001). According to logistic regression analysis, combined detection of miR-34a-5p, miR-148a-3p and Cyfra21-1 provided the highest diagnosis efficiency of 85.07% with sensitivity and specificity reaching 85.45% and 84.71%. Compared with preoperative samples, the level of miR-34a-5p decreased while miR-148a-3p and miR-181a-5p increased in postoperative samples (P < 0.001). Collectively, this first developed, novel absolute quantitative RT-qPCR method exhibits high application value in detecting miRNAs, miR-34a-5p, miR-148a-3p and miR-181a-5p may serve as potential biomarkers in the diagnosis and prognosis of EC, and miR-181a-5p probably could serve as a new biomarker for early EC.


Effect of simple calculation and reading aloud on cognitive function and depression in postoperative older adults.
This study was conducted to determine the effect of simple calculation and reading aloud on postoperative cognitive function and depression level in older adults. The study was a randomised controlled experimental study. A personal information form, Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) were used for data collection. In the evaluation of MMSE and GDS scores of the intervention and control groups 4 weeks after the operation, the differences between the two groups were found to be statistically significant. The results found that simple calculation and reading aloud after surgery had a positive effect on cognitive function and depression level in older people.


Sensitivity and specificity of monocyte distribution width (MDW) in detecting patients with infection and sepsis in patients on sepsis pathway in the emergency department.
Monocyte distribution width (MDW) is a biomarker for the early identification of sepsis. We assessed its accuracy in patients presenting with suspected sepsis in the emergency department (ED). This was a single gate, single centre study in consecutive adults (≥ 18 years) admitted to the ED with suspected sepsis and clinical history compatible with infection, between 01 January and 31 December 2020 (n = 2570). The overall median MDW was 22.0 (IQR 19.3, 25.6). Using Sepsis-3 (qSOFA) to define sepsis, the Area Under Curve (AUC) for a receiver operator characteristic (ROC) relationship was 0.59 (95% CI 0.56, 0.61). Discrimination was similar using other clinical scores, and to that of C-reactive protein. At an MDW cutoff of 20.0, sensitivity was 0.76 (95% CI 0.73, 0.80) and specificity 0.35 (95% CI 0.33, 0.37) for Sepsis-3. MDW showed better performance to discriminate infection, with AUC 0.72 (95% CI 0.69, 0.75). At MDW 20.0, sensitivity for infection was 0.72 (95% CI 0.70, 0.74) and specificity 0.64 (95% CI 0.59, 0.70). A sensitivity analysis excluding coronavirus disease (COVID-19) admissions (n = 552) had no impact on the AUC. MDW distribution at admission was similar for bacteraemia and COVID-19. In this population of ED admissions with a strong clinical suspicion of sepsis, MDW had a performance to identify sepsis comparable to that of other commonly used biomarkers. In this setting, MDW could be a useful additional marker of infection.


Diagnostic utility of CSF1 immunohistochemistry in tenosynovial giant cell tumor for differentiating from giant cell-rich tumors and tumor-like lesions of bone and soft tissue.
Tenosynovial giant cell tumor (TSGCT) is a benign fibrohistiocytic tumor that affects the synovium of joints, bursa, and tendon sheaths and is categorized into localized TSGCT (LTSGCT) and diffuse TSGCT (DTSGCT). LTSGCT and DTSGCT are characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and its translocation partner collagen type VI alpha 3 chain. The fusion gene induces intratumoral overexpression of CSF1 mRNA and CSF1 protein. CSF1 expression is a characteristic finding of TSGCT and detection of CSF1 mRNA and CSF1 protein may be useful for the pathological diagnosis. Although there have been no effective anti-CSF1 antibodies to date, in situ hybridization (ISH) for CSF1 mRNA has been performed to detect CSF1 expression in TSGCT. We performed CSF1 immunohistochemistry (IHC) using anti-CSF1 antibody (clone 2D10) in cases of TSGCT, giant cell-rich tumor (GCRT), and GCRT-like lesion and verified its utility for the pathological diagnosis of TSGCT. We performed CSF1 IHC in 110 cases including 44 LTSGCTs, 20 DTSGCTs, 1 malignant TSGCT (MTSGCT), 10 giant cell tumors of bone, 2 giant cell reparative granulomas, 3 aneurysmal bone cysts, 10 undifferentiated pleomorphic sarcomas, 10 leiomyosarcomas, and 10 myxofibrosarcomas. We performed fluorescence ISH (FISH) for CSF1 rearrangement to confirm CSF1 expression on IHC in TSGCTs. We considered the specimens to have CSF1 rearrangement if a split signal was observed in greater than 2% of the tumor cells. Overall, 50 of 65 TSGCT cases, including 35 of the 44 LTSGCTs and 15 of the 20 DTSGCTs, showed distinct scattered expression of CSF1 in the majority of mononuclear tumor cells. MTSGCT showed no CSF1 expression. Non-TSGCT cases were negative for CSF1. FISH revealed CSF1 rearrangement in 6 of 7 CSF1-positive cases on IHC. On the other hand, FISH detected no CSF1 rearrangement in all CSF1-negative cases on IHC. Thus, the results of IHC corresponded to those of FISH. We revealed characteristic CSF1 expression on IHC in cases of TSGCT, whereas the cases of non-TSGCT exhibited no CSF1 expression. CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking GCRTs and GCRT-like lesions.


Clinical significance of serum bilirubin levels under ursodeoxycholic acid therapy in patients with primary biliary cirrhosis.
We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA. Among UDCA-treated patients, we compared survival free of OLT in patients with normalized SBL (</=17 micromol/L) with those who had persistently elevated SBL. Difference in survival was tested between UDCA-treated patients whose SBL normalized with treatment and placebo patients who had normal baseline SBL. We evaluated, in each treatment group, the prognostic value of 6-month SBL. Survival was estimated using the Kaplan-Meier method and compared by the Cox model. Survival free of OLT was significantly longer in patients who had normalized SBL (P <. 0001; relative risk [RR]: 3.7, UDCA group). Survival free of OLT was not significantly different between UDCA patients with normalized SBL and placebo patients with a normal baseline SBL (P =.69). For several cutoffs of 6-month SBL, RRs of OLT or death were similar in UDCA-treated and placebo patients: the RR of OLT or death associated with a 6-month SBL more than 30 micromol/L was 6.0 for UDCA and 5.7 for placebo groups. In conclusion, normalization of SBL during therapy is associated with improved clinical outcome. SBL under UDCA therapy is a prognostic factor in PBC. SBL under UDCA therapy should be interpreted as in untreated patients.


Segregation of cognitive and emotional function in the prefrontal cortex: a stereotactic meta-analysis.
Imaging studies of major depressive disorder and schizophrenia strongly implicate the prefrontal cortex. Interpretation of such studies is hindered by the limited knowledge of normal functional segregation. Different anatomical regions may be functionally specialised. Elucidating such specialisation may assist design and interpretation of patient studies. In this meta-analysis, 330 emotion induction and cognitive task studies of normal subjects published over the past decade reporting prefrontal activation have been examined. It was hypothesised that emotion induction would result in inferior medial activation and cognitive tasks dorsolateral activation. A significant difference in the pattern of reported activations was found in keeping with this hypothesis. Estimates of most likely reported activation loci for emotion induction and cognitive task studies have been made. In Montreal Neurological Institute (MNI) stereotactic space, these comprise of +/-5, 46, 18 and +/-5, 28, 31 for the medial prefrontal cortex, and +/-42, 28, -16 and +/-54, 28, 18 for the lateral prefrontal cortex, respectively. Additionally, estimates of the boundaries between emotional and cognitive-processing regions have been made. We restricted the effects of various potential sources of bias on the above estimates by attempting to include all relevant studies and independent selection by both authors of at most two activation loci from each study according to prespecified criteria. Such estimates of most likely reported activation loci may allow improved planning, analysis, and interpretation of imaging studies of psychiatric disorder and of normal function.


Biochemical and exoenzymatic properties of Aeromonas species.
One hundred twenty-seven isolates of Aeromonas comprising the three currently recognizable species (A. hydrophila, A. sobria, and A. caviae) were evaluated for biochemical and exoenzymatic properties. Aeromonas species were generally (greater than 90%) characterized as gram-negative fermentative rods that were oxidase-, catalase-, and beta-galactosidase-positive, produced arginine dihydrolase, and failed to decarboxylate ornithine. More than 95% of all isolates tested failed to grow on 6.5% salt or thiosulfate-citrate bile salts agar and were resistant to the vibriostatic agent 0/129. Most Aeromonas species produced acid from hexoses while failing to ferment alcoholic sugars or trisaccharides. In exoenzymatic studies, Aeromonas species were uniformly found to produce several exoenzymes, including amylase, DNase, RNase, esterase, lipase, gelatinase, protease, fibrinolysin, and chitinase. Within the genus, a number of biochemical and enzymatic properties were found to be associated with one or more of the taxonomically recognizable species. These properties included glycoside utilization, Heiberg grouping based upon fermentation of arabinose, sucrose, and mannose, and the elaboration of several extracellular enzymes (elastase, hemolysin, lecithinase, phosphatase). In addition, phenotypic markers previously associated with enterotoxigenic Aeromonas isolates were almost exclusively found among A. hydrophila and A. sobria species, suggesting that these species are the major enteric pathogens.


The expanding role of the nurse practitioner in an academic medical center and its impact on graduate medical education.
Academic medical centers (AMCs) have used nurse practitioners (NPs) for the provision of direct patient care for many years. However, as more NPs are hired to fill in the void created by both the 80-hour work week and the increased demands on attendings' time, their role has evolved in terms of patient care and graduate medical education. We sought to evaluate the expanded role of the NP in our large tertiary AMC to help clarify the interrelationships with the patient care delivery model and GME. Data were collected through interviews of NPs, nurses, attendings, and residents. Data were analyzed to identify trends contributing to successful models of practice and their impact on patient care and graduate medical education (GME). Interviews were completed with 58/74 (78%) NPs employed at our medical center. Anonymous written surveys were completed by 41 (55%) providers. In terms of perceived impact on the role NPs played in GME, 77% of NPs surveyed felt that their role complimented the resident training; 9% felt that their role competed with resident training; and 14% felt that their role had no impact on resident training. We believe that the presence of an experienced NP on a care deliver team can enhance the educational experience of residents as well as provide continuity of patient care in the era of the 80-hour work week.


Comparison of joint versus purebred genomic evaluation in the French multi-breed dairy goat population.
All progeny-tested bucks from the two main French dairy goat breeds (Alpine and Saanen) were genotyped with the Illumina goat SNP50 BeadChip. The reference population consisted of 677 bucks and 148 selection candidates. With the two-step approach based on genomic best linear unbiased prediction (GBLUP), prediction accuracy of candidates did not outperform that of the parental average. We investigated a GBLUP method based on a single-step approach, with or without blending of the two breeds in the reference population. Three models were used: (1) a multi-breed model, in which Alpine and Saanen breeds were considered as a single breed; (2) a within-breed model, with separate genomic evaluation per breed; and (3) a multiple-trait model, in which a trait in the Alpine was assumed to be correlated to the same trait in the Saanen breed, using three levels of between-breed genetic correlations (ρ): ρ = 0, ρ = 0.99, or estimated ρ. Quality of genomic predictions was assessed on progeny-tested bucks, by cross-validation of the Pearson correlation coefficients for validation accuracy and the regression coefficients of daughter yield deviations (DYD) on genomic breeding values (GEBV). Model-based estimates of average accuracy were calculated on the 148 candidates. The genetic correlations between Alpine and Saanen breeds were highest for udder type traits, ranging from 0.45 to 0.76. Pearson correlations with the single-step approach were higher than previously reported with a two-step approach. Correlations between GEBV and DYD were similar for the three models (within-breed, multi-breed and multiple traits). Regression coefficients of DYD on GEBV were greater with the within-breed model and multiple-trait model with ρ = 0.99 than with the other models. The single-step approach improved prediction accuracy of candidates from 22 to 37% for both breeds compared to the two-step method. Using a single-step approach with GBLUP, prediction accuracy of candidates was greater than that based on parent average of official evaluations and accuracies obtained with a two-step approach. Except for regression coefficients of DYD on GEBV, there were no significant differences between the three models.


Effect of foil material on the apparent yield of the 124Xe(p, x)123I reaction.
The effect of the foil material on the recovery of Xe-123 from the irradiation cell used for the measurement of the production of I-123 from the proton reaction on xenon-124 has been studied. The metal used for the foil can have a significant effect on the amount of Xe-123 which can be cryogenically pumped out of the irradiation cell at 30 min after the end of irradiation. Foils made from several metals and alloys were tested. Of these, the effect is most pronounced with "Havar" alloy foil where only 58% of the theoretically available activity was recovered. This effect should be considered and tested in the measurement of reaction cross-sections in irradiation cells and targets which have metal foils.


Sestrin 2 protects against LPS-induced acute lung injury by inducing mitophagy in alveolar macrophages.
Acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) is a critical clinical syndrome with complex pathology and pathogenesis. Since there is no specific treatment for ALI, it is important to study the mechanism of how ALI develop. Sestrin2 (Sesn2) plays a critical role in the regulation of cellular stress response and oxidant defense. However, the potential function of Sesn2 in ALI/ARDS and the associated mechanism remains unclear. Lipopolysaccharide (LPS) induced ALI model was performed in the wild-type and Sesn2 knockout (Sesn2-/-) mice. The nod-like receptor protein 3 (NLRP3) inflammasome, cell pyroptosis and mitophagy were detected by western blots, immunofluorescent staining, flow cytometry. Lung injury were measured by histopathology and electron microscopy. Knockout of Sesn2 enhanced LPS-induced ALI. As detailed in Sesn2-/- mice, NLRP3 inflammasome and cell pyroptosis were increased in lungs; IL-1β and IL-18 in serum and bronchoalveolar lavage fluid (BALF) were further promoted; In the isolated alveolar macrophages from Sesn2-/- mice, mitophagy induced by LPS was markedly inhibited, while reactive oxygen species (ROS), mitochondrial damage and cell pyroptosis were enhanced. Knocking down or overexpressing Sensn2 in J774.A1 cells demonstrated Sesn2 promoted Sequestosome1 (SQSTM1) expression and mitophagy by PTEN-induced putative kinase 1 (Pink1)/Parkin pathway. Sesn2 protected ALI by promoting mitophagy that exerts protection of AMs pyroptosis and negative regulation of NLRP3 inflammasomes. These data indicated Sesn2 might be a potential target for ALI treatment.


The Ad-MD method to calculate NMR shift including effects due to conformational dynamics: The 31 P NMR shift in DNA.
A method for averaging of NMR parameters by molecular dynamics (MD) has been derived from the method of statistical averaging in MD snapshots, benchmarked and applied to structurally dynamic interpretation of the 31 P NMR shift (δ31P ) in DNA phosphates. The method employs adiabatic dependence of an NMR parameter on selected geometric parameter(s) that is weighted by MD-calculated probability distribution(s) for the geometric parameter(s) (Ad-MD method). The usage of Ad-MD for polymers is computationally convenient when one pre-calculated structural dependence of an NMR parameter is employed for all chemically equivalent units differing only in dynamic behavior. The Ad-MD method is benchmarked against the statistical averaging method for δ31P in the model phosphates featuring distinctively different structures and dynamic behavior. The applicability of Ad-MD is illustrated by calculating 31 P NMR spectra in the Dickerson-Drew DNA dodecamer. δ31P was calculated with the B3LYP/IGLO-III/PCM(water) and the probability distributions for the torsion angles adjacent to the phosphorus atoms in the DNA phosphates were calculated using the OL15 force field.


Calciprotein Particle Synthesis Strategy Determines In Vitro Calcification Potential.
Circulating calciprotein particles (CPP), colloids of calcium, phosphate and proteins, were identified as potential drivers of the calcification process in chronic kidney disease. The present study compared CPP produced using different protocols with respect to particle morphology, composition, particle number and in vitro calcification potency. CPP were synthesized with 4.4 mM (CPP-A and B) or 6 mM (CPP-C and D) phosphate and 2.8 mM (CPP-A and B) or 10 mM (CPP-C and D) calcium, with either bovine fetuin-A (CPP-C) or fetal bovine serum (CPP-A, B and D) as a source of protein, and incubated for 7 (CPP-A2) or 14 days (CPP-B2), 12 h (CPP-C2, D2 and B1) or 30 min (CPP-D1). Particle number was determined with nanoparticle tracking and calcium content was measured in CPP preparations and to determine human vascular smooth muscle cell (hVSMC) calcification. Morphologically, CPP-C2 were the largest. Particle number did not correspond to the calcium content of CPP. Both methods of quantification resulted in variable potencies of CPP2 to calcify VSMC, with CPP-B2 as most stable inducer of hVSMC calcification. In contrast, CPP-B1 and D1 were unable to induce calcification of hVSMC, and endogenous CPP derived from pooled serum of dialysis patients were only able to calcify hVSMC to a small extent compared to CPP2.CPP synthesized using different protocols appear morphologically similar, but in vitro calcification potency is dependent on composition and how the CPP are quantified. Synthetic CPP are not comparable to endogenous CPP in terms of the calcification propensity.