Manganese in Madison's drinking water.
Public concern over events of manganese-discolored drinking water and the potential for adverse health effects from exposure to excess manganese reached a high level in 2005. In response, Public Health Madison Dane County, together with the Madison Water Utility, conceived and implemented a public health/water utility strategy to quantify the extent of the manganese problem, determine the potential for adverse human health effects, and communicate these findings to the community. This strategy included five basic parts: taking an inventory of wells and their manganese levels, correlating manganese concentration with turbidity, determining the prevalence and distribution of excess manganese in Madison households, reviewing the available scientific literature, and effectively communicating our findings to the community. The year-long public health/water utility strategy successfully resolved the crisis of confidence in the safety of Madison's drinking water.


Unraveling the architecture of the dorsal raphe synaptic neuropil using high-resolution neuroanatomy.
The dorsal raphe nucleus (DRN), representing the main source of brain's serotonin, is implicated in the pathophysiology and therapeutics of several mental disorders that can be debilitating and life-long including depression, anxiety and autism. The activity of DRN neurons is precisely regulated, both phasically and tonically, by excitatory glutamate and inhibitory GABAergic axons arising from extra-raphe areas as well as from local sources within the nucleus. Changes in serotonin neurotransmission associated with pathophysiology may be encoded by alterations within this network of regulatory afferents. However, the complex organization of the DRN circuitry remains still poorly understood. Using a recently developed high-resolution immunofluorescence technique called array tomography (AT) we quantitatively analyzed the relative contribution of different populations of glutamate axons originating from different brain regions to the excitatory drive of the DRN. Additionally, we examined the presence of GABA axons within the DRN and their possible association with glutamate axons. In this review, we summarize our findings on the architecture of the rodent DRN synaptic neuropil using high-resolution neuroanatomy, and discuss possible functional implications for the nucleus. Understanding of the synaptic architecture of neural circuits at high resolution will pave the way to understand how neural structure and function may be perturbed in pathological states.


Limited therapeutic effect of N-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis.
Alcohol-related steatohepatitis is associated with increased oxidative stress, DNA damage, lipotoxicity, and insulin resistance in liver. As inflammation and oxidative stress can promote insulin resistance, effective treatment with antioxidants, for example, N-acetylcysteine (NAC), may restore ethanol-impaired insulin signaling in the liver. Adult male Sprague-Dawley rats were fed for 130 days with liquid diets containing 0 or 37% ethanol by caloric content, and simultaneously treated with vehicle or NAC. Chow-fed controls were studied in parallel. Liver tissues were used for histopathology, cytokine activation, and insulin/IGF-1 signaling assays. We observed significant positive trends of increasing severity of steatohepatitis (p = 0.016) with accumulation of neutral lipid (p = 0.0002) and triglycerides (p = 0.0004) from chow to control, to the ethanol diet, irrespective of NAC treatment. In ethanol-fed rats, NAC reduced inflammation, converted the steatosis from a predominantly microvesicular to a mainly macrovesicular histological pattern, reduced pro-inflammatory cytokine gene expression, ceramide load, and acid sphingomyelinase activity, and increased expression of IGF-1 receptor and IGF-2 in liver. However, NAC did not abrogate ethanol-mediated impairments in signaling through insulin/IGF-1 receptors, IRS-1, Akt, GSK-3β, or p70S6K, nor did it significantly reduce pro-ceramide or GM3 ganglioside gene expression in liver. Antioxidant treatments reduce the severity of chronic alcohol-related steatohepatitis, possibly because of the decreased expression of inflammatory mediators and ceramide accumulation, but they do not restore insulin/IGF-1 signaling in liver, most likely due to persistent elevation of GM3 synthase expression. Effective treatment of alcohol-related steatohepatitis most likely requires dual targeting of oxidative stress and insulin/IGF resistance.


Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population.
Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.


Species Separation and Hydrogen Streaming upon Shock Release from Polystyrene under Inertial Confinement Fusion Conditions.
Shock release from inertial confinement fusion (ICF) shells poses a great challenge to single-fluid hydrodynamic equations, especially for describing materials composed of different ion species. This has been evidenced by a recent experiment [Haberberger et al., Phys. Rev. Lett. 123, 235001 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.235001], in which low-density plasmas (10^{19} to 10^{20} cm^{-3}) are measured to move far ahead of what radiation-hydrodynamic simulations predict. To understand such experimental observations, we have performed large-scale nonequilibrium molecular-dynamics simulations of shock release in polystyrene (CH) at experimental conditions. These simulations revealed that upon shock releasing from the back surface of a CH foil, hydrogen can stream out of the bulk of the foil due to its mass being lighter than carbon. This released hydrogen, exhibiting a much broader velocity distribution than carbon, forms low-density plasmas moving in nearly constant velocities ahead of the in-flight shell, which is in quantitative agreement with the experimental measurements. Such kinetic effect of species separation is currently missing in single-fluid radiation-hydrodynamics codes for ICF simulations.


Bilateral risk-reducing mastectomy and reconstruction-A 12-year review of methodological trends and outcomes at a tertiary referral centre.
Bilateral risk-reducing mastectomy (BRRM) involves removal of healthy breast tissue to substantially decrease the risk of developing breast cancer in individuals with greater susceptibility due to a strong family history or genetic mutation. This retrospective study evaluates cases of BRRM and associated reconstruction performed at a tertiary centre, with emphasis on mastectomy and reconstructive trends. A retrospective review of all BRRM cases performed between January 2010 and May 2022 was conducted, with two separate cohorts corresponding to the earlier (group 1) and later (group 2) portion of the time-period. Data collected included demographics, genetic test results, family history of breast/ovarian cancer, co-morbidities, mastectomy type, reconstruction type, surgical histopathology findings and post-operative complications. A total of 82 patients (group 1 = 41, group 2 = 41) underwent BRRM. The proportion of nipple-sparing mastectomy increased from 14.6% to 56.1% between the two time periods with a reduction in skin-sparing mastectomies from 75.6% to 20.3% (p<0.001). Of the 80 patients who opted to undergo reconstruction, there was a significant decrease in combined flap-implant reconstructions (19.51% to 0%, p<0.01). Importantly, for implant-only reconstruction, there were significant increases in prepectoral approaches (p = 0.0267) and use of acellular dermal matrix (ADM) (48.15% to 90.63%, p<0.001). This study documents recent increases in nipple-sparing techniques for BRRM compared to more traditional skin-sparing methods. Concurrently, reconstruction following RRM has become predominantly implant-based without a flap, coinciding with more widespread usage of ADM. This is consistent with national trends towards fewer complex autologous procedures.


Muscle energy stores and stroke rates of emperor penguins: implications for muscle metabolism and dive performance.
In diving birds and mammals, bradycardia and peripheral vasoconstriction potentially isolate muscle from the circulation. During complete ischemia, ATP production is dependent on the size of the myoglobin oxygen (O(2)) store and the concentrations of phosphocreatine (PCr) and glycogen (Gly). Therefore, we measured PCr and Gly concentrations in the primary underwater locomotory muscle of emperor penguin and modeled the depletion of muscle O(2) and those energy stores under conditions of complete ischemia and a previously determined muscle metabolic rate. We also analyzed stroke rate to assess muscle workload variation during dives and evaluate potential limitations on the model. Measured PCr and Gly concentrations, 20.8 and 54.6 mmol kg(-1), respectively, were similar to published values for nondiving animals. The model demonstrated that PCr and Gly provide a large anaerobic energy store, even for dives longer than 20 min. Stroke rate varied throughout the dive profile, indicating muscle workload was not constant during dives as was assumed in the model. The stroke rate during the first 30 s of dives increased with increased dive depth. In extremely long dives, lower overall stroke rates were observed. Although O(2) consumption and energy store depletion may vary during dives, the model demonstrated that PCr and Gly, even at concentrations typical of terrestrial birds and mammals, are a significant anaerobic energy store and can play an important role in the emperor penguin's ability to perform long dives.


Homozygous G320V mutation in the HJV gene causing juvenile hereditary haemochromatosis type A. A case report.
While classical hereditary haemochromatosis, usually associated with mutations in the HFE gene, has an adult age onset and a long, progressive evolution, juvenile haemochromatosis, most often associated with mutations in the HJV gene, is a more severe, rapidly progressive condition and has an onset before the age of 30. We report a 26-year old woman with a severe iron overload, affected by hypogonadotropic hypogonadism and moderate dilative cardiomyopathy, in whom the molecular analysis revealed a homozygous genotype for G320V mutation in the HJV gene. As juvenile haemochromatosis is a severe disease, death usually occurring from cardiac involvement, an efficient iron removal from the body strategy should be started as soon as possible, in order to prevent irreversible damage.


The Natural History of pT1 Colorectal Cancer.
Colorectal carcinoma invading the submucosa but not the muscular layer (pT1, early invasive cancer) represents the earliest form of clinically relevant colorectal cancer in most patients. Neoplastic invasion of the submucosa, in fact, opens the way to metastasis via the lymphatic and blood vessels, and the choice between surveillance and major surgery will turn on its metastatic potential. The following histological features predict the risk of metastasis and the different clinical outcomes: grade of differentiation of carcinoma, lymphovascular invasion, state of the resection margin. Microstaging of invasive cancer, namely the width and the depth of submucosal invasion, together with tumor budding at the advancing edge allow the metastatic risk to be further stratified in minimal, low, and high. Different, although morphologically undistinguishable, tumorigenic pathways are supposed to lead to the malignant transformation of colonic mucosa and subsequently to drive the progression from early to advanced cancer: new biomarkers are needed to identify progressive and non-progressive pT1 neoplasia.


Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats.
Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.


Comprehensive two-dimensional gas chromatography for the fast separation and determination of pesticides extracted from human serum.
A comprehensive two-dimensional gas chromatograph with flame ionization detection was constructed and evaluated for the fast separation and analysis of pesticides. A two-stage thermal desorption modulator served as an interface between the two capillary GC columns. By controlling the temperature of the modulator chamber, all sample substances covering a wide polarity and volatility range were modulated without sample breakthrough. Orthogonal separations were achieved with a nonpolar first column and a moderately polar second column. The system allows fast separations of complex mixtures. When we used the method to analyze pesticides extracted from human samples, we achieved complete separation of 15 pesticides in less than 4 min. The flame ionization detector gave detection limits for particular pesticides that ranged from 1.8 to 3.8 pg on-column. The relative standard deviations were from 6.2% to 8.8% over the linear dynamic range.


Preliminary communication on cryptosporidiosis of pigs in Viet-Nam.
Feces were collected from 17 pigs (aged 4-8 weeks) in several farms situated within the region of Hanoi. By coproscopy of the samples, eggs of Ascaris suum and Oesophagostomum dentatum were detected as well as oocysts of Eimeria scabra, E. debliecki, E. perminuta and E. suis, and in addition to it, cryptosporidia to an extend indicating a considerable incidence of this parasitic protozoan in the country.


An assessment of surgical and anesthesia staff at 10 government hospitals in Sierra Leone.
Strengthening workforce capacity to deliver essential surgical and anesthesia care has been identified as a strategy for addressing the unmet burden of morbidity and mortality in under-resourced countries. Sierra Leone is one of the poorest countries in the world and faces the challenge of stretching limited resources to provide appropriate health care for a population of 6 million. To investigate the training of surgical and anesthesia staff in Sierra Leone and to build an evidence base for future health care policy and training programs tailored to local needs. Health care professionals who conduct surgery or deliver anesthesia at 10 of the 23 government hospitals in Sierra Leone were surveyed regarding training and clinical practices. This study surveyed 36 of 70 surgical staff (51%) and 38 of 68 nurse specialists (56%) nationally. Descriptive analysis of demographic details, training levels, and reported needs for future development. Thirty-six surgeons were surveyed in study hospitals, of whom the majority had limited surgical specialization training, whereas most anesthesia was provided by 47 nurse specialists. All consultants had postgraduate qualifications, but 4 of 6 medical superintendents (67%) and all medical officers lacked postgraduate surgical qualifications or formal surgical specialist training. The number of trained anesthesia staff increased after the introduction of the Nurse Anesthesia Training Program in 2008, funded by the United Nations Fund for Population Activities, increasing the number from 2 to 47 anesthesia staff based at the study hospitals. Although 32 of 37 nurse anesthetists (86%) reported having attended training workshops, 30 of 37 (>80%) described anesthesia resources as "poor," reporting a critical need for anesthesia machines and continual oxygen supply. Of the 37, 25 specifically mentioned the need for a better-functioning anesthesia machine and 16 mentioned the need for oxygen. To address unmet surgical need in the long term, accredited local surgical specialization programs are required; training of nonphysician surgical practitioners may offer a short-term solution. To develop safe anesthesia care, governments and donors should focus on providing health care professionals with essential equipment and resources.


Mass discrimination during prolonged weightlessness.
Thresholds for mass discrimination under zero gravity in flight were found to be higher by a factor of about 1.8 than those for weight discrimination before flight. This suggests that humans are not as sensitive to inertial mass as they are to weight, and that adaptation can only partially compensate for loss of gravity. Weight discrimination thresholds were raised for 2 or 3 days after flight, suggesting an aftereffect of adaptation to weightlessness.


Neuropathophysiology, Genetic Profile, and Clinical Manifestation of Mucolipidosis IV-A Review and Case Series.
Mucolipidosis type IV (MLIV) is an ultra-rare lysosomal storage disorder caused by biallelic mutations in MCOLN1 gene encoding the transient receptor potential channel mucolipin-1. So far, 35 pathogenic or likely pathogenic MLIV-related variants have been described. Clinical manifestations include severe intellectual disability, speech deficit, progressive visual impairment leading to blindness, and myopathy. The severity of the condition may vary, including less severe psychomotor delay and/or ocular findings. As no striking recognizable facial dysmorphism, skeletal anomalies, organomegaly, or lysosomal enzyme abnormalities in serum are common features of MLIV, the clinical diagnosis may be significantly improved because of characteristic ophthalmological anomalies. This review aims to outline the pathophysiology and genetic defects of this condition with a focus on the genotype-phenotype correlation amongst cases published in the literature. The authors will present their own clinical observations and long-term outcomes in adult MLIV cases.


Synthesis and evaluation of estrogen receptor ligands with bridged oxabicyclic cores containing a diarylethylene motif: estrogen antagonists of unusual structure.
A new series of ligands for the estrogen receptor (ER) based on a three-dimensional structural motif consisting of a bridged oxabicyclic core (7-oxabicyclo[2.2.1]heptene or heptadiene) were synthesized and examined for their receptor binding activity and as regulators of transcription through the two ER subtypes, ER alpha and ER beta. The prototypical ligands also contain a 1,2-diarylethylene motif, common to many nonsteroidal estrogens, as an embellishment on the oxabicyclic core. Thus, these ligands bear peripheral groups typically found in ER ligands, built here upon an overall three-dimensional core topology that is unusual for these targets. Most of these compounds were conveniently synthesized by a Diels-Alder reaction of various 3,4-diarylfurans with a variety of dienophiles, neat and under mild conditions in the absence of catalysts. Some of the synthesized compounds display good binding affinity for the ER, and in transcription assays, the highest affinity compounds are antagonists on both ERs. Molecular modeling studies suggest a structural basis for the antagonist activity of these compounds. These compounds, based on the bicyclo[2.2.1]core system, expand the structural diversity of ligands that can be antagonists for the estrogen receptors.


Identification of Small-Molecule Inhibitors of Neutral Ceramidase (nCDase) via Target-Based High-Throughput Screening.
There is interest in developing inhibitors of human neutral ceramidase (nCDase) because this enzyme plays a critical role in colon cancer. There are currently no potent or clinically effective inhibitors for nCDase reported to date, so we adapted a fluorescence-based enzyme activity method to a high-throughput screening format. We opted to use an assay whereby nCDase hydrolyzes the substrate RBM 14-16, and the addition of NaIO4 acts as an oxidant that releases umbelliferone, resulting in a fluorescent signal. As designed, test compounds that act as ceramidase inhibitors will prevent the hydrolysis of RBM 14-16, thereby decreasing fluorescence. This assay uses a 1536-well plate format with excitation in the blue spectrum of light energy, which could be a liability, so we incorporated a counterscreen that allows for rapid selection against fluorescence artifacts to minimize false-positive hits. The high-throughput screen of >650,000 small molecules found several lead series of hits. Multiple rounds of chemical optimization ensued with improved potency in terms of IC50 and selectivity over counterscreen assays. This study describes the first large-scale high-throughput optical screening assay for nCDase inhibitors that has resulted in leads that are now being pursued in crystal docking studies and in vitro drug metabolism and pharmacokinetics (DMPK).


Multisensory evoked potentials in experimental and applied neurotoxicology.
The development of evoked potential techniques in clinical neurology and neurotoxicology is outlined and specific procedures used in experimental animal neurotoxicology are detailed. Illustrative results from the SRI laboratory are presented, with discussion of the advantages, limitations, clinical relevance, and future applications of evoked potentials in neurotoxicology.


Imbalance of Peripheral Blood T Helper Type 17 Responses in Patients with Vitiligo.
There is growing evidence to suggest that Th cells play pivotal roles in a variety of chronic inflammatory diseases, including vitiligo. However, the exact role of different subsets of Th cells in the pathogenesis of vitiligo is still a question. The purpose of present study was to determine the mRNA expression level of Th17 master transcription factor retinoic acid receptor-related orphan receptors gamma (RORɣt) and cytokine mRNA and protein expression profiles of Th17 cells. 22 patients with vitiligo and 22 normal subjects were enrolled in the study. Gene expression profiles of freshly isolated peripheral blood mononuclear cells (PBMCs) were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). Plasma concentrations of IL-17A and IL-22 were also assayed using ELISA kits. The results showed that RORɣt, IL-17A and IL-22 mRNA expression were increased in patients remarkably compared to healthy controls (p<0.05). Furthermore, plasma IL-17A and IL-22 levels were also higher in vitiligo patients versus controls (p<0.001). These data suggest that a deregulated Th17 adaptive immune response may contribute to the pathogenesis of vitiligo.


Human Herpesvirus 6: an Evolving Story.
First isolated in 1986 from patients with lymphoproliferative disorders, human herpesvirus 6 (HHV-6) is a B-herpesvirus with two variants: HHV-6A and HHV-6B. HHV-6B is the major causal pathogen of exanthem subitum, a predominantly benign exanthematous disease of infants with occasional complications in the central nervous system. Infection with HHV-6 is common among the general population and the virus mainly seems to be transmitted from mother to infant via saliva. Following primary infection, HHV-6 persists latently and can reactivate in immunocompromised hosts, such as in individuals with AIDS or in transplant or multiple sclerosis patients where it possibly causes encephalitis and pneumonitis. Its precise role in these conditions is not well understood and further study is needed.


A Dyadic Approach to Understanding Associations Between Job Stress, Marital Quality, and Dyadic Coping for Dual-Career Couples in Iran.
In Iran, dual-career couples face many stressors due to their demands of balancing work and family. Moreover, the experience of this stress can negatively affect partners' martial quality. Recent studies have shown the positive impact of dyadic coping on well-being; however, a majority of this research has been conducted with Western cultures. As such, there is a dearth of literature on understanding how supportive and common dyadic coping may have a positive association with work-family stress for couples in Iran. Using a sample of 206 heterosexual dual-career couples from Iran, this study examines the associations between job stress and marital quality, and possible moderating effects of common and perceived partner supportive dyadic coping. As predicted, job stress was negatively associated with marital quality, and this association with further moderated by gender, such that women who experienced greater job stress also reported lower marital quality. Additionally, dyadic coping moderated the association between job stress and marital quality. Common dyadic coping attenuated the negative association between job stress and marital quality. The findings shed light on the possible beneficial effects of teaching supportive and common dyadic coping techniques to dual-career couples in Iran.


Association Between Inflammatory Markers and Myocardial Fibrosis.
Inflammation promotes adverse ventricular remodeling. T1 mapping has been used to noninvasively assess interstitial myocardial fibrosis. We examined the association of baseline markers of systemic inflammation with interstitial myocardial fibrosis measured by extracellular volume fraction (ECV) and native T1 mapping at 10-year follow-up in the MESA (Multi-Ethnic Study of Atherosclerosis). Seven hundred seventy-two participants had complete baseline data and underwent cardiac magnetic resonance imaging. All analyses were stratified by sex. Multivariable linear regression models were constructed to assess the associations of baseline CRP (C-reactive protein), IL (interleukin)-6, and fibrinogen with native T1 time and ECV. Longer native T1 times and higher percentages of ECV represent increasing myocardial fibrosis. A 1-SD increment of log-transformed IL-6 levels was associated with 0.4% higher ECV in men (β=0.4; P=0.05). CRP and fibrinogen were not associated to ECV. A 1-SD increment in the log-transformed CRP levels was associated with 4.9 ms higher native T1 (β=4.9; P=0.03). In women, the inflammatory markers did not demonstrate association with native T1 nor ECV. Higher IL-6 and CRP levels are associated with increased interstitial myocardial fibrosis assessed by cardiac magnetic resonance in men. However, no inflammatory markers were associated to myocardial fibrosis in women.


Patients with chronic three-vessel disease in a 15-year follow-up study: genetic and non-genetic predictors of survival.
Genetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated. Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin-angiotensin-aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained from the national insurance registry. All data were available in the case of 150 patients with 3VD. Statistical analysis used stepwise Cox regression with dominant, recessive, or additive mode of genetic expression. Involved variables included age, sex, BMI, blood pressure, diabetes, ejection fraction, left main stenosis, previously diagnosed coronary stenosis, myocardial infarction in personal history, and coronary bypass along with polymorphisms pre-selected by log-rank tests. Out of the 23 polymorphisms, four were included in the model construction. SNP in the IL-6 gene rs1800795 (-174 G/C) has been found to be a significant predictor of survival. This SNP was in a linkage disequilibrium with rs1800797 (-597 G/A) in the same gene (D'=1.0), which was also found to constitute a significant predictor of survival when rs1800795 was not included in the model construction. Age, increased BMI, diabetes, low EF, and left main stenosis were also significant predictors in all models. Age, increased BMI, diabetes, low ejection fraction, left main stenosis, and genetic variation in the IL-6 promoter were established as significant independent risk factors for the survival of patients with three-vessel disease.


Lower extremity kinematics of athletics curve sprinting.
Curve running requires the generation of centripetal force altering the movement pattern in comparison to the straight path run. The question arises which kinematic modulations emerge while bend sprinting at high velocities. It has been suggested that during curve sprints the legs fulfil different functions. A three-dimensional motion analysis (16 high-speed cameras) was conducted to compare the segmental kinematics of the lower extremity during the stance phases of linear and curve sprints (radius: 36.5 m) of six sprinters of national competitive level. Peak joint angles substantially differed in the frontal and transversal plane whereas sagittal plane kinematics remained unchanged. During the prolonged left stance phase (left: 107.5 ms, right: 95.7 ms, straight: 104.4 ms) the maximum values of ankle eversion (left: 12.7°, right: 2.6°, straight: 6.6°), hip adduction (left: 13.8°, right: 5.5°, straight: 8.8°) and hip external rotation (left: 21.6°, right: 12.9°, straight: 16.7°) were significantly higher. The inside leg seemed to stabilise the movement in the frontal plane (eversion-adduction strategy) whereas the outside leg provided and controlled the motion in the horizontal plane (rotation strategy). These results extend the principal understanding of the effects of curve sprinting on lower extremity kinematics. This helps to increase the understanding of nonlinear human bipedal locomotion, which in turn might lead to improvements in athletic performance and injury prevention.


Equity matrix for kidney transplant allocation.
There is a general agreement that the distribution of kidneys for transplantation should balance utility criteria with justice. Moreover, a kidney allocation system must be based on transparent policies and seen as an ongoing process. This study aims to present an allocation system grounded on an equity matrix that balances the criteria of utility and justice. Synthetic data for a waiting list with 2000 transplant candidates and a pool of 280 donors were generated. A color priority system, the Eurotransplant (ET) kidney allocation system, and the proposed Equity Matrix (EQM) allocation system were compared after 1000 iterations of kidney allocations. Distributions of variables like the age difference, Human Leukocyte Antigens (HLA) mismatches (mmHLA), recipients' time on dialysis, cPRA, and a transplant score obtained by different allocation models were compared graphically and with Cohen's d effect size. For the analyzed variables, when we compare only the selected recipients from ET with the selected recipients from the EQM neutral model, we can conclude that the former model selects more hypersensitized recipients, a higher number of 65+ years' old recipients with 65+ years' old donors and higher number of recipients with 0 mmHLA. While recipients from EQM neutral are slightly older, have a lower age difference with their donors, have a lower number of mmHLA, are less likely to have 6 mmHLA with their donors, and have more time on dialysis. The proposed EQM model attempts to provide a simple, transparent, and equitable response to a complex question with results that outperform established practices.


A new molecular link between defective autophagy and erythroid abnormalities in chorea-acanthocytosis.
Chorea-acanthocytosis is one of the hereditary neurodegenerative disorders known as the neuroacanthocytoses. Chorea-acanthocytosis is characterized by circulating acanthocytes deficient in chorein, a protein of unknown function. We report here for the first time that chorea-acanthocytosis red cells are characterized by impaired autophagy, with cytoplasmic accumulation of active Lyn and of autophagy-related proteins Ulk1 and Atg7. In chorea-acanthocytosis erythrocytes, active Lyn is sequestered by HSP90-70 to form high-molecular-weight complexes that stabilize and protect Lyn from its proteasomal degradation, contributing to toxic Lyn accumulation. An interplay between accumulation of active Lyn and autophagy was found in chorea-acanthocytosis based on Lyn coimmunoprecipitation with Ulk1 and Atg7 and on the presence of Ulk1 in Lyn-containing high-molecular-weight complexes. In addition, chorein associated with Atg7 in healthy but not in chorea-acanthocytosis erythrocytes. Electron microscopy detected multivesicular bodies and membrane remnants only in circulating chorea-acanthocytosis red cells. In addition, reticulocyte-enriched chorea-acanthocytosis red cell fractions exhibited delayed clearance of mitochondria and lysosomes, further supporting the impairment of authophagic flux. Because autophagy is also important in erythropoiesis, we studied in vitro CD34+-derived erythroid precursors. In chorea-acanthocytosis, we found (1) dyserythropoiesis; (2) increased active Lyn; (3) accumulation of a marker of autophagic flux and autolysososme degradation; (4) accumlation of Lamp1, a lysosmal membrane protein, and LAMP1-positive aggregates; and (5) reduced clearance of lysosomes and mitochondria. Our results uncover in chorea-acanthocytosis erythroid cells an association between accumulation of active Lyn and impaired autophagy, suggesting a link between chorein and autophagic vesicle trafficking in erythroid maturation.


Evaluation of the epidemiological relevance of variable-number tandem-repeat genotyping of Mycobacterium bovis and comparison of the method with IS6110 restriction fragment length polymorphism analysis and spoligotyping.
Sources of Mycobacterium bovis contamination remain unclear for many cases of animal and human disease. A major limitation is the lack of sufficiently informative or epidemiologically well evaluated molecular methods for typing. Here, we report an evaluation of a high-throughput method based on 29 mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) loci to genotype 127 M. bovis isolates from cattle from 77 different Belgian farms, representative of a nationwide collection obtained from 1995 to 2003. MIRU-VNTR stability was demonstrated by analyzing a series of 74 isolates in total, obtained from different animals from a single farm or from different farms with an identified epidemiological link. The genotyping results and the genotypic diversity (h) were compared with those obtained by IS6110 restriction fragment length polymorphism (RFLP) analysis and spoligotyping. Among 68 isolates with no known epidemiological link, MIRU-VNTR typing discriminated better than either RFLP analysis or spoligotyping, [corrected] taken individually (32 versus 16 and 17 genotypes; h = 0.91 versus 0.73 and 0.85, respectively) or in combination (32 versus 28 genotypes; h = 0.91 versus 0.92). Maximal resolution was already achieved with a subset of 9 loci. The observed congruence of the genetic relationships based on IS6110 RFLP analysis, spoligotyping, and MIRU-VNTR markers is consistent with a clonal population structure of M. bovis. These results support MIRU-VNTR typing as a convenient and discriminatory technique for analysis of the population structure of M. bovis in much greater detail and for addressing some still unresolved issues in the epidemiology of the pathogen.


Organ biodistribution of Germanium-68 in rat in the presence and absence of [(68)Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body radiation dosimetry.
Positron Emission Tomography (PET) and in particular gallium-68 ((68)Ga) applications are growing exponentially worldwide contributing to the expansion of nuclear medicine and personalized management of patients. The significance of (68)Ga utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the monographs that might limit the use of the generators and consequently expansion of (68)Ga applications and that is the limit of 0.001% of Germanium-68 ((68)Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of (68)Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and justification of the (68)Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [(68)Ge]GeCl4 in the absence or presence of [(68)Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). (68)Ge(IV) was evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose estimates indicated that the kidneys were the dose-limiting organs (185±54 μSv/MBq for female and 171±38 μSv/MBq for male) and the total effective dose was 15.5±0.1 and 10.7±1.2 μSv/MBq, respectively for female and male. The results of this dosimetry study conclude that the (68)Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without exposing the patient to harm given the small absorbed doses to normal organs and fast excretion.


Treatment and outcomes of precocious puberty: an update.
Precocious puberty is a common problem affecting up to 29 per 100,000 girls per year. The earliest identified neuroendocrine change in early puberty thus far is increased kisspeptin secretion from the arcuate nucleus and the anteroventral paraventricular nucleus of the hypothalamus. The regulation of kisspeptin secretion is not well understood, but neurokinin B and dynorphin provide autocrine regulation. The etiologies of precocious puberty may be subdivided into GnRH-dependent and GnRH-independent causes. GnRH-dependent precocious puberty, often called central precocious puberty (CPP), is usually treated with GnRH analogs. Newer developments in the treatment of CPP include expanded data on the safety and efficacy of the subdermal histrelin implant, which is useful for long-term treatment, although removal may be difficult in some cases. Preliminary data suggest that the implant may be left in place for up to 2 years without loss of biochemical suppression. In the last 2 years, more data have been published concerning extended-release leuprolide acetate injections that indicate that the 11.25-mg dose may not provide full biochemical suppression but may clinically suppress signs of puberty, including the accelerated growth velocity and advanced skeletal maturation seen in CPP. Treatment options for familial male-limited precocious puberty and McCune-Albright syndrome are expanding as well, although data are preliminary. Long-term outcome studies of CPP indicate overall good menstrual and reproductive function, but the prevalence of polycystic ovary syndrome may be higher than in the general population. Remarkably few studies have evaluated the behavioral and psychological outcomes of precocious puberty, in contrast to early normal maturation. Additional outcome studies of endocrine, metabolic, and psychological effects of CPP are clearly needed.


Thrombolytic efficacy of native recombinant staphylokinase on femoral artery thrombus of rabbits.
To investigate the thrombolytic efficacy, ideal dosage and administration of native recombinant staphylokinase (r-SAK). Forty New Zealand rabbits were randomly assigned into the control, r-SAK low-dose, medial-dose, high dose, single bolus, allied therapy, recombinant streptokinase (r-SK) and urokinase (UK) groups. The right femoral artery thrombosis models were made by balloon injury, and 120 min after the injury, the thrombolytic agents were infused through the rabbits' parallel-ear vein. (1) 2 h after balloon injury, the pulse pressures of the right femoral arteries reduced to 0 or less than 10% of that of left femoral arteries in all groups; (2) after thrombolytic therapy, the pulse pressures in some of the femoral arteries markedly enhanced to more than 50% of that of left femoral arteries; (3) the reopening rates in the r-SAK medial and high dose groups were significantly higher than that of the control. The reopening rate of the same dose native r-SAK was significant higher than that of UK and r-SK; (4) the patency score of the right femoral arteries tended to be better in the r-SAK medial and high-dose groups than that of the low-dose group, and the time to reopening in the allied therapy group tended to be shorter. (1) r-SAK has a definite thrombolytic effect on the femoral artery thrombus of rabbits; (2) single bolus is an effective manner of r-SAK therapy, and r-SAK allied therapy with heparin may shorten the time to recanalization; (3) the efficacy of the same dose native r-SAK was superior to that of r-SK and UK.


Fast-starting after a breath: air-breathing motions are kinematically similar to escape responses in the catfish Hoplosternum littorale.
Fast-starts are brief accelerations commonly observed in fish within the context of predator-prey interactions. In typical C-start escape responses, fish react to a threatening stimulus by bending their body into a C-shape during the first muscle contraction (i.e. stage 1) which provides a sudden acceleration away from the stimulus. Recently, similar C-starts have been recorded in fish aiming at a prey. Little is known about C-starts outside the context of predator-prey interactions, though recent work has shown that escape response can also be induced by high temperature. Here, we test the hypothesis that air-breathing fish may use C-starts in the context of gulping air at the surface. Hoplosternum littorale is an air-breathing freshwater catfish found in South America. Field video observations reveal that their air-breathing behaviour consists of air-gulping at the surface, followed by a fast turn which re-directs the fish towards the bottom. Using high-speed video in the laboratory, we compared the kinematics of the turn immediately following air-gulping performed by H. littorale in normoxia with those of mechanically-triggered C-start escape responses and with routine (i.e. spontaneous) turns. Our results show that air-breathing events overlap considerably with escape responses with a large stage 1 angle in terms of turning rates, distance covered and the relationship between these rates. Therefore, these two behaviours can be considered kinematically comparable, suggesting that air-breathing in this species is followed by escape-like C-start motions, presumably to minimise time at the surface and exposure to avian predators. These findings show that C-starts can occur in a variety of contexts in which fish may need to get away from areas of potential danger.


Assessment of Respiratory Function in Infants and Young Children Wearing Face Masks During the COVID-19 Pandemic.
Face masks have been associated with effective prevention of diffusion of viruses via droplets. However, the use of face masks among children, especially those aged younger than 3 years, is debated, and the US Centers for Disease Control and American Academy of Physicians recommend the use of face mask only among individuals aged 3 years or older. To examine whether the use of surgical facial masks among children is associated with episodes of oxygen desaturation or respiratory distress. This cohort study was conducted from May through June 2020 in a secondary-level hospital pediatric unit in Italy. Included participants were 47 healthy children divided by age (ie, group A, aged ≤24 months, and group B, aged >24 months to ≤144 months). Data were analyzed from May through June 2020. All participants were monitored every 15 minutes for changes in respiratory parameters for the first 30 minutes while not wearing a surgical face mask and for the next 30 minutes while wearing a face mask. Children aged 24 months and older then participated in a walking test for 12 minutes. Changes in respiratory parameters during the use of surgical masks were evaluated. Among 47 children, 22 children (46.8%) were aged 24 months or younger (ie, group A), with 11 boys (50.0%) and median (interquartile range [IQR]) age 12.5 (10.0-17.5) months, and 25 children (53.2%) were aged older than 24 months to 144 months or younger, with 13 boys (52.0%) and median (IQR) age 100.0 (72.0-120.0) months. During the first 60 minutes of evaluation in the 2 groups, there was no significant change in group A in median (IQR) partial pressure of end-tidal carbon dioxide (Petco2; 33.0 [32.0-34.0] mm Hg; P for Kruskal Wallis = .59), oxygen saturation (Sao2; 98.0% [97.0%-99.0%]; P for Kruskal Wallis = .61), pulse rate (PR; 130.0 [115.0-140.0] pulsations/min; P for Kruskal Wallis = .99), or respiratory rate (RR; 30.0 [28.0-33.0] breaths/min; P for Kruskal Wallis = .69) or for group B in median (IQR) Petco2 (36.0 [34.0-38.0] mm Hg; P for Kruskal Wallis = .97), Sao2 (98.0% [97.0%-98.0%]; P for Kruskal Wallis = .52), PR (96.0 [84.0-104.5] pulsations/min; P for Kruskal Wallis test = .48), or RR (22.0 [20.0-25.0] breaths/min; P for Kruskal Wallis = .55). After the group B walking test, compared with before the walking test, there was a significant increase in median (IQR) PR (96.0 [84.0-104.5] pulsations/min vs 105.0 [100.0-115.0] pulsations/min; P < .02) and RR (22.0 [20.0-25.0] breaths/min vs 26.0 [24.0-29.0] breaths/min; P < .05). This cohort study among infants and young children in Italy found that the use of facial masks was not associated with significant changes in Sao2 or Petco2, including among children aged 24 months and younger.


Reproducibility of spectral-domain optical coherence tomography RNFL map for glaucomatous and fellow normal eyes in unilateral glaucoma.
To compare the reproducibility of the optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness map between glaucomatous and fellow normal eyes of unilateral glaucoma patients. In this prospective case-control study, Cirrus HD-OCT was performed for 79 unilateral glaucoma patients 3 times on the first visit and on 3 subsequent visits within a 2-month period. Test-retest standard deviation (TRT-SD) and tolerance limit based on the 1.645×√2×TRT-SD formula were derived for RNFL thicknesses at the respective superpixels of the RNFL thickness map. The TRT-SDs and tolerance limits of the glaucomatous eyes (TRT-SD: 2.75 to 20.25 μm; tolerance limits: 6.40 and 47.11 μm) were significantly smaller than those of the fellow normal eyes (TRT-SD: 2.73 to 26.49 μm; tolerance limits: 6.35 and 61.63 μm) in the superotemporal, inferotemporal, and superonasal areas (P <0.05). The TRT-SDs in most areas showed a significant positive correlation with the RNFL thicknesses (P<0.05). The test-retest variabilities of the Cirrus HD-OCT RNFL thickness map of the glaucomatous eyes were lower than those of the fellow normal eyes, especially in areas of high diagnostic importance. Moreover, variability was positively correlated with the baseline RNFL thicknesses. Therefore, adjusting the tolerance limits on the basis of the baseline RNFL thickness values might help improve the ability to recognize progression. Further prospective studies on this issue are warranted.


Stability over time of hematological variables in 197 children with sickle cell anemia.
One hundred ninety-seven children with sickle cell anemia were followed for 4 years at the Wayne State Comprehensive Sickle Cell Center to evaluate the stability of the hematological variables (Hb, Hct, RBC count, MCV, %HbF and %HBA2) over time. The mean values of the hematological measurements taken during three separate 16-month intervals were used to represent an individual's values. The correlations of the hematological variables between intervals ranged from a low of 0.46 for %HBA2 to a high of 0.91 for %HbF. Correlations that spanned two intervals (an average of 32 months) were of the same magnitude as those that spanned only one interval (an average of 16 months), suggesting that there was no decrease in the degree of stability of these variables as the time between measurements increased. The stability of the correlations between variables within intervals, and the stability of the coefficients of the first two principal components of the six hematological variables over time suggested that the relationships among variables were also stable. In a recent report [Odenheimer et al, 1983], we used the values of the six hematological variables collected at an individual's first visit to the sickle cell center to identify four hematologically distinct subgroups of children. In the current report, we found that as many as 83% of the individuals remained in the same subgroup in at least two of the three follow-up intervals, suggesting that the factors that contributed to this classification were the result of stable, rather than transient phenomena.


Chronic psychological stress impairs recovery of muscular function and somatic sensations over a 96-hour period.
The primary aim of this study was to determine whether chronic mental stress moderates recovery of muscular function and somatic sensations: perceived energy, fatigue, and soreness, in a 4-day period after a bout of strenuous resistance exercise. Undergraduate resistance training students (n = 31; age, 20.26 ± 1.34 years) completed the Perceived Stress Scale and the Undergraduate Stress Questionnaire, a measure of life event stress. At a later visit, they performed an acute heavy-resistance exercise protocol (10 repetition maximum [RM] leg press test plus 6 sets: 80-100% of 10RM). Maximal isometric force (MIF), perceived energy, fatigue, and soreness were assessed in approximately 24-hour intervals after exercise. Recovery data were analyzed with hierarchical linear modeling growth curve analysis. Life event stress significantly moderated linear (p = 0.027) and squared (p = 0.031) recovery of MIF. This relationship held even when the model was adjusted for fitness, workload, and training experience. Perceived energy (p = 0.038), fatigue (p = 0.040), and soreness (p = 0.027) all were moderated by life stress. Mean perceived stress modulated linear and squared recovery of MIF (p < 0.001) and energy (p = 0.004) but not fatigue or soreness. In all analyses, higher stress was associated with worse recovery. Stress, whether assessed as life event stress or perceived stress, moderated the recovery trajectories of muscular function and somatic sensations in a 96-hour period after strenuous resistance exercise. Therefore, under conditions of inordinate stress, individuals may need to be more mindful about observing an appropriate length of recovery.


[A comparative assessment of the efficacy of thiophosphamide electrophoresis and ultrasound in the combined therapy of reactive arthritis].
The results of the treatment of patients suffering from rheumatoid arthritis with ultrasound (group I), thiophosphamide electrophoresis (group II), ultrasound and thiophosphamide (group III) and with medicamentous agents alone (group IV) are compared. The positive therapeutic effect was recorded in patients of all 4 groups, with that effect being most remarkable in group III.


Involvement of transducer of regulated cAMP response element-binding protein activity on corticotropin releasing hormone transcription.
We have recently shown that phospho-cAMP response element-binding protein (CREB) is essential but not sufficient for activation of CRH transcription, suggesting the requirement of a coactivator. Here, we test the hypothesis that the CREB coactivator, transducer of regulated CREB activity (TORC), is required for activation of CRH transcription, using the cell line 4B and primary cultures of hypothalamic neurons. Immunohistochemistry and Western blot experiments in 4B cells revealed time-dependent nuclear translocation of TORC1,TORC 2, and TORC3 by forskolin [but not by the phorbol ester, phorbol 12-myristate 13-acetate (PMA)] in a concentration-dependent manner. In reporter gene assays, cotransfection of TORC1 or TORC2 potentiated the stimulatory effect of forskolin on CRH promoter activity but had no effect in cells treated with PMA. Knockout of endogenous TORC using silencing RNA markedly inhibited forskolin-activated CRH promoter activity in 4B cells, as well as the induction of endogenous CRH primary transcript by forskolin in primary neuronal cultures. Coimmunoprecipitation and chromatin immunoprecipitation experiments in 4B cells revealed association of CREB and TORC in the nucleus, and recruitment of TORC2 by the CRH promoter, after 20-min incubation with forskolin. These studies demonstrate a correlation between nuclear translocation of TORC with association to the CRH promoter and activation of CRH transcription. The data suggest that TORC is required for transcriptional activation of the CRH promoter by acting as a CREB coactivator. In addition, cytoplasmic retention of TORC during PMA treatment is likely to explain the failure of phorbolesters to activate CRH transcription in spite of efficiently phosphorylating CREB.


Alexithymia in Patients With Substance Use Disorders and Its Relationship With Psychiatric Comorbidities and Health-Related Quality of Life.
Background: Alexithymia frequently correlates with several psychiatric disorders, including substance use disorder (SUD). However, most studies reporting the associations between alexithymia and psychiatric disorders have been performed in populations without SUD. This research, therefore, evaluates alexithymia in Spanish patients with SUD and the relationship among alexithymia, psychiatric comorbidities, psychological symptoms/traits, SUD variables, and health-related quality of life (HRQoL). Methodology: A cross-sectional study was conducted with 126 Spanish outpatients with SUD (75.4% males; mean age 43.72 ± 14.61 years), correlating their alexithymia levels (using the Toronto Alexithymia Scale 20 [TAS-20]) to their psychiatric comorbidities, psychological symptoms/traits, SUD variables, and HRQoL. Results: Alexithymia was significantly higher in patients who had cannabis use disorder. Higher alexithymia scores were also related to higher levels of depression, anxiety, impulsivity, and lower HRQoL. After multivariate analysis, trait anxiety, impulsivity, and the physical component summary of the HRQoL were found to be independently related to alexithymia. Conclusions: SUD patients with higher alexithymia levels have more frequently psychiatric comorbidities, present specific psychological features, and have worse HRQoL. Hence, it is important to evaluate these factors and offer more accurate psychotherapeutic approaches for this patient population.


The relationships of cognitive coping and pain control beliefs to pain and adjustment among African-American and Caucasian women with rheumatoid arthritis.
Ethnic groups may experience or report pain differently; thus, we compared ethnic differences on pain coping strategies and control beliefs, and the relationships of these variables to health status, among women with rheumatoid arthritis (RA). Using a sample of 100 women (48 African-American, 52 Caucasian), we related pain coping strategies and control beliefs to pain severity, activity levels, and affective state, controlling for socioeconomics, behavioral impairment, and disease activity. Ethnic groups did not differ in pain severity or negative affect, but African-Americans were less physically active. African-Americans used more coping techniques involving diverting attention and praying/hoping; Caucasians used more coping techniques involving ignoring pain. The relationships of praying/hoping and reinterpreting pain to RA adjustment differed by ethnic group. In contrast, ignoring pain, coping statements, and stronger control beliefs predicted better health status, and diverting attention predicted more pain for all patients. There are ethnic differences in the use of coping strategies that should be acknowledged when helping RA patients cope with their disease, but control beliefs and several coping strategies predict pain and adjustment, regardless of ethnicity.


Secondary metabolites from the Chinese liverwort Cephaloziella kiaeri.
Sixteen new clerodane diterpenoids, cephaloziellins A-P (1-16), and two known analogues (17 and 18) were isolated from an EtOH extract of the Chinese liverwort Cephaloziella kiaeri. The structures of the new compounds were elucidated from extensive spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 5, 9, and 15 were confirmed by single-crystal X-ray diffraction analyses. The absolute configurations of all new compounds were established by comparing experimental and calculated electronic circular dichroism spectra.


Scanning electron microscopy of human and rhesus monkey kidneys.
Human kidney biopsies fixed by immersion fixation and a rhesus monkey kidney fixed by vascular perfusion were critical point-dried and studied by scanning electron microscopy. The surface morphologies of the parietal and visceral epithelial cells and cells lining the uriniferous tubules are described. Many instructive views of these cells as well as some new nephronal features are presented. This study demonstrated that both scanning and transmission electron microscopy may be undertaken on the same biopsy sample. In view of these results, the possibility of using scanning electron microscopy for routine diagnosis of human biopsies is discussed.


Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro.
Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 μM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer's disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression.


Distribution of growth cones and synapses in developing laminar and interlaminar regions of the dorsal lateral geniculate nucleus.
In the present study, we quantified the distribution of growth cones and synapses in 2 developing layers, as well as in the intervening interlaminar space of the dorsal lateral geniculate nucleus (dLGN) in tree shrews. Our goal was to gain insight into mechanisms involved in the segregation of dLGN cells into layers during development. We sacrificed tree shrews before (P0), during (P4 and P7), and after (P15) laminar segregation as well as at maturity (P90). The dLGN from each animal was sectioned horizontally, and all tissue for analysis was blocked from the middle third of the nucleus along the dorsoventral axis. Each micrograph was coded and blindly scored for the number of growth cones and synapses in layers 4 and 5 and the intervening interlaminar space. We also measured each growth cone and classified synapse type. Statistical analyses of these data reveal that neither growth cones nor synapses are significantly more common in the interlaminar space early in the period of laminar segregation (P4). By nearly a week after the interlaminar space can first be distinguished (P7), there are more growth cones in the interlaminar space than in the layers, but this difference is no longer present at (P15). These results suggest that, although neuropil development at the laminar borders may not play a role in the onset of laminar segregation, it may contribute to the widening of the interlaminar spaces once this process has begun. In addition, growth cones continuously decrease in number and become less bulbous and more linear in shape with development. Synapses, on the other hand, continuously increase in number with age and pass through a transient period characterized by heavy spinous terminations.


Antibodies directed against antigens on the endothelium of peritubular capillaries in patients with rejecting renal allografts.
This study was undertaken to examine the humoral immune response against endothelial antigens of the donor kidney in human renal allograft recipients. Sera from 61 transplant recipients who received 62 grafts were studied for the presence of circulating endothelial antibodies (CEAb) using an indirect immunofluorescence technique with a pretransplant biopsy of the graft as a substrate. IgG antibodies directed against the endothelium of peritubular capillaries were found in the sera of 6 of the 10 patients with graft rejection within 7 weeks after transplantation, whereas these antibodies were not found in the absence of rejection (P less than 0.001). Immunofluorescence studies of post-transplant biopsies showed IgG along the endothelium of peritubular capillaries only in the grafts of patients with CEAb. Eluates from these grafts contained IgG antibodies that bound to the endothelium of the donor as shown by the indirect immunofluorescence technique. Absorption of endothelial antibody (EAb)-positive sera with human platelets or Wistar strain rat erythrocytes showed that the EAb were not directed against serologically defined HLA antigens or against heterophile antigens on rat erythrocytes. We conclude from this study that the presence of antibodies directed against endothelial antigens is associated with poor graft prognosis and that these antibodies may be responsible for the rejection process.


Effects of shades of a multilayered zirconia on light transmission, monomer conversion, and bond strength of resin cement.
To evaluate the influence of shades of a multilayered zirconia on light transmission, resin cement degree of conversion, and shear bond strength of resin cement. The light transmission through opaque (OPQ) and translucent (TNS) regions of Katana UTML zirconia (Kuraray Noritake Dental) were evaluated for using a spectroradiometer (n = 5). Degree of conversion of dual-cure resin cement (Panavia V5, Kuraray Noritake Dental) was measured after light-activation through OPQ or TNS regions and direct exposure. Composition of the zirconia was analyzed with energy dispersive x-ray spectroscopy (EDS). Shear bond strength (SBS) was evaluated on the OPQ and TNS regions after 24 h and 1 year from specimen preparation (n = 15). The OPQ region produced higher irradiance loss (95.1%) than TNS one (92.9%), and lower degree of conversion (52.4%) than TNS (71.2%) at 24 h post-light activation. EDS analysis did not show differences on the microstructure of the OPQ and TNS regions. There were no significant differences on the SBS between zirconia regions. For both zirconia regions, a significant reduction on the SBS occurred after aging, being 31.7% for OPQ and 38% for TNS. Both OPQ and TNS regions affected the light transmission through the multilayered zirconia. The OPQ region yielded the highest light attenuation and the lowest degree of conversion of resin cement. Different regions of the zirconia did not influence the SBS. Clinical significance Although opaque and translucent regions of the multilayered zirconia reduced the light transmission from LED curing unit and the degree of conversion of resin cement, the regions did not affect the resin cement adhesion.


Third harmonic generation microscopy of cells and tissue organization.
The interaction of cells within their microenvironmental niche is fundamental to cell migration, positioning, growth and differentiation in order to form and maintain complex tissue organization and function. Third harmonic generation (THG) microscopy is a label-free scatter process that is elicited by water-lipid and water-protein interfaces, including intra- and extracellular membranes, and extracellular matrix structures. In applied life sciences, THG delivers a versatile contrast modality to complement multi-parameter fluorescence, second harmonic generation and fluorescence lifetime microscopy, which allows detection of cellular and molecular cell functions in three-dimensional tissue culture and small animals. In this Commentary, we review the physical and technical basis of THG, and provide considerations for optimal excitation, detection and interpretation of THG signals. We further provide an overview on how THG has versatile applications in cell and tissue research, with a particular focus on analyzing tissue morphogenesis and homeostasis, immune cell function and cancer research, as well as the emerging applicability of THG in clinical practice.


Nurses' spiritual care practices: becoming less religious?
Research indicates that nurses do not consistently provide spiritual care, feel ill equipped to do so, and there is a lack of information as to the type of spiritual care practices nurses use. This exploratory descriptive study surveyed nurses (N = 123) about their spiritual care practices and perceptions of effectiveness, followed by qualitative interviews with volunteers (n = 5) from the surveyed group. The nurses favored spiritual interventions that are not overtly religious, but conveyed concern and support, such as listening and providing comforting touch.


Divalent phosphate electrode.
Divalent phosphate ion activities can be measured in dilute aqueous solutions in the physiological pH range (7.0 to 7.5) with a liquid ionexchange membrane electrode system; the organic ion exchanger consists of an amine chloride membrane. Reference solutions may be either aqueous chloride or bicarbonate solutions. An essentially Nernstian slope is obtained.


Advanced MR imaging in Lhermitte-Duclos disease: moving closer to pathology and pathophysiology.
Lhermitte-Duclos disease (LDD, dysplastic gangliocytoma) is an extremely rare cerebellar lesion of uncertain etiology. The debate as to whether it constitutes a neoplastic, malformative, or hamartomatous lesion is still continuing. In this report we explore the usefulness of susceptibility-weighted imaging (SWI), diffusion weighted imaging (DWI), perfusion imaging, and chemical shift imaging (CSI) in demonstrating the pathology and pathophysiology in two patients with LDD. MR imaging of the brain and the cervicodorsal spine was performed on a 1.5-T scanner in a 47-year-old woman presenting with numbness and paresthesia of both upper and lower limbs, and in a 17-year-old male with right frontal headache associated with neck pain. Routine imaging in the first patient showed a left-side cerebellar mass with characteristic 'tiger-striped' thick folia associated with Chiari I malformation, tonsillar herniation and cervicodorsal syringomyelia and in the second patient a right cerebellar mass with similar findings. The SWI demonstrated the characteristic deep running veins between the folia, which is thought to be the cause for vascular contrast enhancement. Diffusion showed a T2 shine-through effect with mild increased diffusivity, and perfusion showed increase in relative cerebral blood volume, relative cerebral blood flow, and mean transit time in the lesion. MR spectroscopy demonstrated reduction in metabolites and a prominent lactate peak in both the patients. The pathological and pathophysiological significance of these findings is discussed. MRI with the newer imaging capabilities can demonstrate the pathology and pathophysiology in Lhermitte-Duclos disease better. SWI helps in detecting the veins around the thickened folia.


Spatial and temporal parameters of self-selected and fast walking speeds in healthy community-living adults aged 72-98 years.
There is limited data about typical performance for spatial and temporal measures of self-selected walking speed (SSWS) and fast walking speeds (FWS) for healthy adults older than 75 years. This study reports both velocity and spatial and temporal characteristics of walking by age group and gender for 118 community-living adults between the ages of 72 and 98 years, mean age 84.8 (5.3) years, participating in a functional assessment clinic held at their continuing care retirement community. Three trials of SSWS and 3 trials of FWS were captured using the GAITRite system (CIR Systems, Inc., Havertown, Pennsylvania). Velocity, normalized velocity, and other spatial and temporal parameters were calculated by GAITRite software. Independent ttests were used to evaluate differences by age and gender in demographic and anthropometric characteristics, and vital signs. Mean of 3 trials was used to develop performance values by age group and gender. Analysis of variance with appropriate post hoc testing was used to identify differences in gait characteristics by age and gender. There were no differences in anthropomorphic or vital signs by age group; men where taller and heavier as would be expected. There was a consistent age effect for both SSWS and FWS; gait velocity decreased as age increased, with significant differences between all decades of age. There was a significant gender effect, with men walking faster than women at SSWS and FWS. Even after normalizing SSWS and FWS to leg length, men walked faster than females. Data reported in this study of generally healthy older adults can be used by rehabilitation professionals to develop goals for functional walking speed and determine readiness for discharge for patients intending to return to community-living settings following their rehabilitation.


Protected areas and agricultural expansion: Biodiversity conservation versus economic growth in the Southeast of Brazil.
The conversion of natural ecosystems to agricultural land and urban areas plays a threat to the protected areas and the natural ecosystems conservation. The aim of this paper is to provide an analysis of the agricultural expansion and its impact on the landscape spatial and temporal patterns in a buffer zone of a protected area located in the transition zone between the Atlantic Forest and Cerrado, in the State of São Paulo, Brazil. The land use and land cover were mapped between 1971 and 2008 and landscape metrics were calculated to provide a spatiotemporal analysis of the forest structure and the expansion of the croplands. The results showed that the landscape patterns were affected by the economic cycles. The predominant crop surrounding the protected area is sugar cane, which increased by 39% during this period, followed by citrus. This landscape change is connected to the Brazilian oil crisis in 1973. The rapid expansion of sugar cane was largely driven by Brazil's biofuel program, the "Proálcool" (pro-alcohol), a project in 1975 that mixed ethanol with gas for automotive fuel. The forest loss occurred mainly between 1971 and 1988, decreasing the forest cover from 17% in 1971 to 12.7% in 2008. Most of the forest patches are smaller than 50 ha and has low connectivity. Throughout the years, the fragments in the buffer zone have become smaller and with an elongated shape, and the park has become isolated. This forest fragmentation process and the predominance of monoculture lands in the buffer zone threaten the protected areas, and can represent a barrier for these areas to provide the effective biodiversity conservation. The measures proposed are necessary to ensure the capability of this ecosystem to sustain its original biodiversity.


Environmentally modulated phosphorylation and dynamics of proteins in photosynthetic membranes.
Recent advances in vectorial proteomics of protein domains exposed to the surface of photosynthetic thylakoid membranes of plants and the green alga Chlamydomonas reinhardtii allowed mapping of in vivo phosphorylation sites in integral and peripheral membrane proteins. In plants, significant changes of thylakoid protein phosphorylation are observed in response to stress, particularly in photosystem II under high light or high temperature stress. Thylakoid protein phosphorylation in the algae is much more responsive to the ambient redox and light conditions, as well as to CO(2) availability. The light-dependent multiple and differential phosphorylation of CP29 linker protein in the green algae is suggested to control photosynthetic state transitions and uncoupling of light harvesting proteins from photosystem II under high light. The similar role for regulation of the dynamic distribution of light harvesting proteins in plants is proposed for the TSP9 protein, which together with other recently discovered peripheral proteins undergoes specific environment- and redox-dependent phosphorylation at the thylakoid surface. This review focuses on the environmentally modulated reversible phosphorylation of thylakoid proteins related to their membrane dynamics and affinity towards particular photosynthetic protein complexes.


THYMUS: ITS LIMITED ROLE IN THE RECOVERY OF HOMOGRAFT RESPONSE IN IRRADIATED MICE.
Adult mice subjected to thymectomy or sham thymectomy received lethal irradiation and subsequent protective infusion of syngeneic bone marrow. Thirty days later they received allogeneic and xenogeneic skin grafts. Donors of the xenogeneic grafts were rats. The thymectomized mice rejected the grafts of rat skin only slightly later than the controls did; in contrast, the time of retention of allogeneic grafts was significantly longer in the thymectomized mice.


Mild Encephalitis/Encephalopathy with Reversible Splenial Lesion (MERS) due to Cytomegalovirus: Case Report and Review of the Literature.
Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by a transient mild encephalopathy and MRI findings of a reversible lesion in the splenium of corpus callosum (SCC). It is classified in MERS type I and MERS type II, depending on the involvement of SCC alone or also other white matter areas. The syndrome mainly affects children and young adults; the prognosis is favorable with complete or nearly complete neurological and radiological resolution within days or weeks. The vast majority of the cases described in the literature involve Asian and Australian children. The exact pathophysiology is unknown; however, infectious-related MERS (in particular virus associated MERS) remains the most common cause of reversible splenial lesions in childhood. To the best of our knowledge, there is only one published case of MERS associated with cytomegalovirus (CMV) infection involving an Australian child. We present here the first case of a CMV-related MERS in a European Caucasian child.


Inflammatory cytokines in eyes with uveal melanoma and relation with macrophage infiltration.
The presence of an inflammatory phenotype, characterized by an increased expression of HLA antigens and an immunologic infiltrate, carries a bad prognosis in uveal melanoma. This study was conducted to determine whether the aqueous humor (AqH) from eyes with uveal melanoma contains inflammatory cytokines and whether their presence is associated with inflammation. Immediately after enucleation, AqH was obtained from 37 eyes containing uveal melanoma. Samples were stored at -80°C until use. Fifteen different cytokines were measured with a multiplex bead array. Intratumoral macrophages were analyzed by immunohistochemistry and immunofluorescence staining. The presence of specific cytokines was compared with histopathologic, genetic, and clinical tumor characteristics, as well as patient survival. Several cytokines showed significantly higher expression in the AqH of uveal melanoma-containing eyes than in the AqH of eyes undergoing cataract surgery. MCP-3 was associated with the presence of CD68(+) macrophages. Correlations were found between some cytokine levels and a few known prognostic factors of uveal melanoma, but cytokine levels were not of predictive value for survival. Uveal melanoma-containing eyes often carry increased levels of inflammation-related cytokines in their AqH. However, the presence of most specific cytokines was not related to the presence of macrophages, clinical or histopathologic parameters, or prognosis.


Alternatives to in-person exercise classes and training in Germany during the first COVID-19 lockdown.
COVID-19 containment efforts in most countries included temporary closure of all non-essential services, such as sports and exercise facilities. Also in Germany, sports clubs (SC) had to close for about 2 months starting mid-March 2020. The aim of the present study was to assess what alternatives German SC developed to in-person exercise classes and training. We conducted an anonymous online survey among large German SC. Invitation was sent to 178 SC, 61 data sets could be analyzed. A total of 92% of SC have offered alternatives to in-person exercise classes and training, most of which were digital. Reasons for not offering any alternatives were the lack of financial, personal or technical resources. The large majority (82.1%) of the SC have also allowed non-club members free access to digital alternatives, and 69.6% considered keeping this freely accessible even after the restrictions have been lifted. Almost three quarters (72.3%) of the sport clubs have received no support from their regional umbrella sports organization. In light of the dynamic development of the COVID-19 pandemic, SC must be prepared to offer alternatives to in-person exercise classes and training also on the middle term. These efforts should be supported by sports organizations and communities.


Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons.
Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease. To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12. Prospective study performed from 1993 to 2002. Geographically defined biracial community in Chicago, Ill. A total of 3718 residents, 65 years and older, who completed 2 to 3 cognitive assessments and a food frequency questionnaire. Change in cognitive function measured at baseline and 3-year and 6-year follow-ups, using the average z score of 4 tests: the East Boston Tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test. High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors. The rate of cognitive decline among persons in the top fifth of total folate intake (median, 742 microg/d) was more than twice that of those in the lowest fifth of intake (median, 186 microg/d), a statistically significant difference of 0.02 standardized unit per year (P = .002). A faster rate of cognitive decline was also associated with high folate intake from food (P for trend = .04) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers (beta = -.03, P<.001). High total B12 intake was associated with slower cognitive decline only among the oldest participants. High intake of folate may be associated with cognitive decline in older persons. These unexpected findings call for further study of the cognitive implications of high levels of dietary folate in older populations.


Increased proliferation of skin cells by sublethal doses of sodium lauryl sulfate.
Most quantitative in vitro approaches to determine irritancy have examined the potential of compounds to decrease biological functions or inhibit growth of cells. Irritants, however, are known to generally have the opposite effect in vivo, i.e. to stimulate cell division. This property has not been directly studied in vitro. We examined the ability of sublethal concentrations of sodium lauryl sulfate (SLS) to stimulate cultured keratinocyte and fibroblast proliferation in vitro. The growth of keratinocytes, without added growth factors, continuously exposed to SLS for 4 days was stimulated approximately 89% compared to control. Keratinocytes exposed to SLS for 1 or 18 h were stimulated 36 and 12%, respectively, over the next 4 days of growth. Subconfluent fibroblasts were also stimulated approximately 38%. Confluent fibroblasts were stimulated 40%. All stimulations were maximal between 10(-8) and 10(-5) M added SLS. Media conditioned by keratinocytes exposed to 10(-8) M SLS were able to increase the growth of naive keratinocytes by 117%. In all experiments doses of SLS > 10(-5) M inhibited cell growth. We conclude that sublethal doses of SLS can stimulate the growth of cultured keratinocytes and fibroblasts. The stimulation of growth seen may be related to the stimulation observed in in vivo irritation.


High-side digitally current controlled biphasic bipolar microstimulator.
Electrical stimulation of nervous tissue has been extensively used as both a tool in experimental neuroscience research and as a method for restoring of neural functions in patients suffering from sensory and motor disabilities. In the central nervous system, intracortical microstimulation (ICMS) has been shown to be an effective method for inducing or biasing perception, including visual and tactile sensation. ICMS also holds promise for enabling brain-machine-brain interfaces (BMBIs) by directly writing information into the brain. Here we detail the design of a high-side, digitally current-controlled biphasic, bipolar microstimulator, and describe the validation of the device in vivo. As many applications of this technique, including BMBIs, require recording as well as stimulation, we pay careful attention to isolation of the stimulus channels and parasitic current injection. With the realized device and standard recording hardware-without active artifact rejection-we are able to observe stimulus artifacts of less than 2 ms in duration.


Dominant role of the MyD88-dependent signaling pathway in mediating early endotoxin-induced murine ileus.
TLR4 ligation by pathogen-associated molecular patterns, such as Gram-negative bacteria-derived LPS, triggers a nonhematopoietic cell-mediated ileus during early endotoxemia. Our objective was to investigate the quantitative contributions of the two downstream signaling pathways of TLR4, namely the adapter proteins myeloid differentiation primary response gene 88 (MyD88) and Toll-IL-1-resistance (TIR) domain-containing adaptor-inducing IFN-beta (TRIF). Six hours after intraperitoneal injection of highly purified LPS (UP-LPS, 5 mg/kg), in vivo gastrointestinal transit and intestinal muscularis gene transcripts of inflammatory mediators chemokine (C-X-C motif) ligand 10, synonymous IP-10 (CXCL10), granulomonocyte colony stimulating factor (GM-CSF, synonymous CSF-2), IL-1beta, IL-6, IL-10, and inducible NO synthase (iNOS) were assessed in mice with transgenic loss-of-function for MyD88 or TRIF. LPS-induced MyD88 and TRIF mRNA upregulation was quantified within the intestinal muscularis of TLR4-competent and TLR4-mutant mice, and MyD88 mRNA levels were additionally measured in TLR4 bone marrow chimeras. MyD88 deficiency completely protected mice from early endotoxin-induced ileus, while TRIF deficiency partially ameliorated ileus severity. LPS induction of the primary downstream signaling element MyD88 was TLR4 dependent and was derived in equal amounts from both the hematopoietic and the nonhematopoietic cells. Conversely, no induction of TRIF mRNA was detectable. Significant gene induction of all inflammatory mediators was dependent on intracellular signal transduction by MyD88, while the TRIF MyD88-independent pathway predominantly regulated the molecular levels of CXCL10. In summary, MyD88 and TRIF are nonredundant signaling pathways in early endotoxin-induced rodent ileus, but MyD88 is the essential adaptor molecule for transduction of early TLR4-induced ileus and inflammatory signaling. The dependency of ileus on individual adaptor protein pathways is also reflected in the manifestation of specific molecular inflammatory events within the intestinal muscularis externa.


Confirmatory factor analysis of the Infant Feeding Styles Questionnaire in Latino families.
Parent feeding practices affect risk of obesity in children. Latino children are at higher risk of obesity than the general population, yet valid measure of feeding practices, one of which is the Infant Feeding Styles Questionnaire (IFSQ), have not been formally validated in Spanish. To validate the IFSQ among Latino families, we conducted confirmatory factor analysis of pressuring, restrictive, and responsive feeding constructs from the IFSQ. The IFSQ was administered at the 12-month visit in the Greenlight study, a multi-center cluster randomized trial to prevent obesity. Parents were included if they were of Latino origin (n = 303) and completed an English or Spanish language modified IFSQ (without the indulgence construct). Scores from nine sub-constructs of the IFSQ were compared between English and Spanish language versions. We tested reliability with Cronbach's alpha coefficients and performed confirmatory factor analysis to examine factor loadings and goodness of fit characteristics, modifying constructs to achieve best fit. Of 303 parents completing the IFSQ, 84% were born outside the US, and 74% completed the IFSQ in Spanish. Reliability coefficients ranged from 0.28 to 0.61 for the laissez-faire sub-constructs and from 0.58 to 0.83 for the pressuring, restrictive, and responsive sub-constructs. Results for all coefficients were similar between participants responding to an English and Spanish version of the IFSQ. Goodness of fit indices ranged from CFI 0.82-1 and RMSEA 0.00-0.31, and the model performed best in pressuring-soothing (CFI 1.0, RMSEA 0.00) and restrictive-amount (CFI 0.98, RMSEA 0.1) sub-constructs. In a sample of Latino families, pressuring, restrictive, and responsive constructs performed well. The modified IFSQ in both English and Spanish-speaking Latino families may be used to assess parenting behaviors related to early obesity risk in this at-risk population.


The effect of weekend and after-hours surgery on morbidity and mortality rates in pediatric neurosurgery patients.
Several studies have indicated that the 30-day morbidity and mortality risks are higher among pediatric and adult patients who are admitted on the weekends. This "weekend effect" has been observed among patients admitted with and for a variety of diagnoses and procedures, including myocardial infarction, pulmonary embolism, ruptured abdominal aortic aneurysm, stroke, peptic ulcer disease, and pediatric surgery. In this study, morbidity and mortality outcomes for emergency pediatric neurosurgical procedures carried out on the weekend or after hours are compared with emergency surgical procedures performed during regular weekday business hours. A retrospective analysis of operative data was conducted. Between December 1, 2011, and August 20, 2014, a total of 710 urgent or emergency neurosurgical procedures were performed at Texas Children's Hospital in children younger than than 18 years of age. These procedures were then stratified into 3 groups: weekday regular hours, weekday after hours, and weekend hours. By cross-referencing these events with a prospectively collected morbidity and mortality database, the impact of the day and time on complication incidence was examined. Outcome metrics were compared using logistic regression models. The weekday regular hours and after-hours (weekday after hours and weekends) surgery groups consisted of 341 and 239 patients and 434 and 276 procedures, respectively. There were no significant differences in the types of cases performed (p = 0.629) or baseline preoperative health status as determined by American Society of Anesthesiologists classifications (p = 0.220) between the 2 cohorts. After multivariate adjustment and regression, children undergoing emergency neurosurgical procedures during weekday after hours or weekends were more likely to experience complications (p = 0.0227). Weekday after-hours and weekend emergency pediatric neurosurgical procedures are associated with significantly increased 30-day morbidity and mortality risk compared with procedures performed during weekday regular hours.


A window into third-generation sequencing.
First- and second-generation sequencing technologies have led the way in revolutionizing the field of genomics and beyond, motivating an astonishing number of scientific advances, including enabling a more complete understanding of whole genome sequences and the information encoded therein, a more complete characterization of the methylome and transcriptome and a better understanding of interactions between proteins and DNA. Nevertheless, there are sequencing applications and aspects of genome biology that are presently beyond the reach of current sequencing technologies, leaving fertile ground for additional innovation in this space. In this review, we describe a new generation of single-molecule sequencing technologies (third-generation sequencing) that is emerging to fill this space, with the potential for dramatically longer read lengths, shorter time to result and lower overall cost.


Complementary therapies and health promotion.
Nurses have an important role to play in health promotions and it is important that they have a comprehensive knowledge and understanding of the theories of health promotion and conventional interventions. However, they are increasingly likely to be asked about the efficacy of non-conventional interventions and the likelihood of these interventions being of value to the client. This paper offers a review of the evidence to support the role of complementary therapies as adjunctive treatments to enable nurses to discuss their use with their clients as part of their health choice options.


In vivo bioluminescence imaging for prolonged survival of transplanted human neural stem cells using 3D biocompatible scaffold in corticectomized rat model.
Stem cell-based treatment of traumatic brain injury has been limited in its capacity to bring about complete functional recovery, because of the poor survival rate of the implanted stem cells. It is known that biocompatible biomaterials play a critical role in enhancing survival and proliferation of transplanted stem cells via provision of mechanical support. In this study, we noninvasively monitored in vivo behavior of implanted neural stem cells embedded within poly-l-lactic acid (PLLA) scaffold, and showed that they survived over prolonged periods in corticectomized rat model. Corticectomized rat models were established by motor-cortex ablation of the rat. F3 cells expressing enhanced firefly luciferase (F3-effLuc) were established through retroviral infection. The F3-effLuc within PLLA was monitored using IVIS-100 imaging system 7 days after corticectomized surgery. F3-effLuc within PLLA robustly adhered, and gradually increased luciferase signals of F3-effLuc within PLLA were detected in a day dependent manner. The implantation of F3-effLuc cells/PLLA complex into corticectomized rats showed longer-lasting luciferase activity than F3-effLuc cells alone. The bioluminescence signals from the PLLA-encapsulated cells were maintained for 14 days, compared with 8 days for the non-encapsulated cells. Immunostaining results revealed expression of the early neuronal marker, Tuj-1, in PLLA-F3-effLuc cells in the motor-cortex-ablated area. We observed noninvasively that the mechanical support by PLLA scaffold increased the survival of implanted neural stem cells in the corticectomized rat. The image-guided approach easily proved that scaffolds could provide supportive effect to implanted cells, increasing their viability in terms of enhancing therapeutic efficacy of stem-cell therapy.


Maximal Glycemic Difference, the Possible Strongest Glycemic Variability Parameter to Predict Mortality in ICU Patients.
This retrospective study aimed to determine the correlation of blood glucose and glycemic variability with mortality and to identify the strongest glycemic variability parameter for predicting mortality in critically ill patients. A total of 528 patients admitted to the medical intensive care unit were included in this study. Blood glucose levels during the first 24 hours of admission were recorded and calculated to determine the glycemic variability. Significant glycemic variability parameters, including the standard deviation, coefficient of variation, maximal blood glucose difference, and J-index, were subsequently compared between intensive care unit survivors and nonsurvivors. A binary logistic regression was performed to identify independent factors associated with mortality. To determine the strongest glycemic variability parameter to predict mortality, the area under the receiver operating characteristic of each glycemic variability parameter was determined, and a pairwise comparison was performed. Among the 528 patients, 17.8% (96/528) were nonsurvivors. Both survivor and nonsurvivor groups were clinically comparable. However, nonsurvivors had significantly higher median APACHE-II scores (23 [21, 27] vs. 18 [14, 22]; p < 0.01) and a higher mechanical ventilator support rate (97.4% vs. 74.9%; p < 0.01). The mean blood glucose level and significant glycemic variability parameters were higher in nonsurvivors than in survivors. The maximal blood glucose difference yielded a similar power to the coefficient of variation (p = 0.21) but was significantly stronger than the standard deviation (p = 0.005) and J-index (p = 0.006). Glycemic variability was independently associated with intensive care unit mortality. Higher glycemic variability was identified in the nonsurvivor group regardless of preexisting diabetes mellitus. The maximal blood glucose difference and coefficient of variation of the blood glucose were the two strongest parameters for predicting intensive care unit mortality in this study.


Cryo-EM structure of a bacteriophage M13 mini variant.
Filamentous bacteriophages package their circular, single stranded DNA genome with the major coat protein pVIII and the minor coat proteins pIII, pVII, pVI, and pIX. Here, we report the cryo-EM structure of a ~500 Å long bacteriophage M13 mini variant. The distal ends of the mini phage are sealed by two cap-like complexes composed of the minor coat proteins. The top cap complex consists of pVII and pIX, both exhibiting a single helix structure. Arg33 of pVII and Glu29 of pIX, located on the inner surface of the cap, play a key role in recognizing the genome packaging signal. The bottom cap complex is formed by the hook-like structures of pIII and pVI, arranged in helix barrels. Most of the inner ssDNA genome adopts a double helix structure with a similar pitch to that of the A-form double-stranded DNA. These findings provide insights into the assembly of filamentous bacteriophages.


Community health worker navigation to improve allostatic load: The Integrated Population Health (IPOP) study.
Social determinants of health (SDOH) and cumulative stress contribute to chronic disease development. The physiological response to repeated stressors typical of lower-income environments can be measured through allostatic load - a composite measure of cardiovascular, metabolic, and immune variables. Healthcare systems have employed patient navigation for social and medical needs to improve SDOH that has demonstrated limited impact on chronic disease outcomes. This study evaluates a novel community health worker navigation intervention developed using behavioral theories to improve access to social and medical services and provide social support for poverty stressed adults. The Integrated Population Health Study (IPOP) study is a randomized, parallel two arm study evaluating community health worker navigation in addition to an existing integrated population health program (IPOP CHW) as compared to Usual Care (population health program only, IPOP) on allostatic load and chronic disease risk factors. IPOP CHW participants receive a 10-month navigation intervention. From 381 screened individuals, a total of 202 participants (age 58.15 ± 12.03 years, 74.75 % female, 79.21 % Black/African American, 17.33 % Hispanic) were enrolled and randomized to IPOP CHW (n = 100) or IPOP Only (n = 102). This study will evaluate whether CHW navigation, using a structured intervention based on health behavior theories, can effectively guide poverty stressed individuals to address social and medical needs to improve allostatic load-a composite of cumulative stress and physiological responses. Healthcare systems, nonprofit organizations, and governmental entities are interested in addressing SDOH to improve health, thus developing evidence-based interventions could have broad clinical and policy implications.