Rural Affordable Care Act outreach and enrollment: what we learned during the first marketplace open enrollment period.
As part of the Patient Protection and Affordable Care Act (Affordable Care Act) of 2010, 2 new opportunities for health care coverage were established for many uninsured individuals beginning on January 1, 2014. The first opportunity was through Medicaid expansion where states had the opportunity to expand Medicaid coverage to individuals with household incomes up to 133% of the federal poverty level. The second opportunity was through the establishment of Health Insurance Marketplaces where individuals could purchase private health plans and potentially qualify for financial assistance in paying for their plans. The Office of Rural Health Policy (ORHP) provided supplemental grant awards to help stimulate Affordable Care Act outreach and education efforts in rural communities that were being served by the Rural Health Care Services Outreach (Outreach) Grant Program. As a result, Outreach grantees enrolled 9,300 rural Americans during the initial Open Enrollment period. Valuable outreach and enrollment lessons were learned from rural communities based on discussions with the Outreach grantees who received the supplemental funding. These lessons will help rural communities prepare for the next Open Enrollment period.


Comparative whole-genome hybridization reveals genomic islands in Brucella species.
Brucella species are responsible for brucellosis, a worldwide zoonotic disease causing abortion in domestic animals and Malta fever in humans. Based on host preference, the genus is divided into six species. Brucella abortus, B. melitensis, and B. suis are pathogenic to humans, whereas B. ovis and B. neotomae are nonpathogenic to humans and B. canis human infections are rare. Limited genome diversity exists among Brucella species. Comparison of Brucella species whole genomes is, therefore, likely to identify factors responsible for differences in host preference and virulence restriction. To facilitate such studies, we used the complete genome sequence of B. melitensis 16M, the species highly pathogenic to humans, to construct a genomic microarray. Hybridization of labeled genomic DNA from Brucella species to this microarray revealed a total of 217 open reading frames (ORFs) altered in five Brucella species analyzed. These ORFs are often found in clusters (islands) in the 16M genome. Examination of the genomic context of these islands suggests that many are horizontally acquired. Deletions of genetic content identified in Brucella species are conserved in multiple strains of the same species, and genomic islands missing in a given species are often restricted to that particular species. These findings suggest that, whereas the loss or gain of genetic material may be related to the host range and virulence restriction of certain Brucella species for humans, independent mechanisms involving gene inactivation or altered expression of virulence determinants may also contribute to these differences.


Dysfunction of TRIM21 in interferon signature of systemic lupus erythematosus.
TRIM21 is an E3 ubiquitin ligase for interferon regulatory factors (IRFs) that are involved in innate and acquired immunity. Here, we evaluated the role of TRIM21 in the interferon (IFN) signature of systemic lupus erythematosus (SLE). Twenty SLE patients and 24 healthy controls were enrolled in this study. We analyzed mRNA expression of TRIM21, type I IFN, and IFN-inducible genes in peripheral blood mononuclear cell (PBMC). The protein levels of IRFs were assessed by Western blotting in PBMCs cultured with or without MG-132. The expression of TRIM21 mRNA and protein was significantly higher in SLE PBMCs as compared to healthy controls. There was a correlation between TRIM21 mRNA expression and SLE activities. In contrast to a negative correlation between mRNA expression level of TRIM21 and those of type I IFNs in healthy controls, we found a positive correlation between them in anti-TRIM21 antibody-positive SLE patients. Neither positive nor negative correlation was observed in the autoantibody-negative SLE patients. Western-blotting analysis revealed impaired ubiquitin-dependent proteasomal degradation of IRFs in SLE PBMCs. Our study showed ubiquitin-dependent proteasomal degradation of IRFs was impaired in anti-TRIM21 antibody-dependent and -independent fashions, leading to amplification of IFN signature in SLE.


Development of genetic and genomic evaluation for wellness traits in US Holstein cows.
In March 2016, Zoetis Genetics offered the first commercially available evaluation for wellness traits of Holstein dairy cattle. Phenotypic data on health events, pedigree, and genotypes were collected directly from producers upon obtaining their permission. Among all recorded health events, 6 traits were chosen to be included in the evaluation: mastitis, metritis, retained placenta, displaced abomasum, ketosis, and lameness. Each trait was defined as a binary event, having a value of 1 if a cow has been recorded with a disorder at any point during the lactation and zero otherwise. The number of phenotypic records ranged from 1.8 million for ketosis to 4.1 million for mastitis. Over 14 million pedigree records and 114,216 genotypes were included in the evaluation. All traits were analyzed using univariate threshold animal model with repeated observations, including fixed effect of parity and random effects of herd by year by season of calving, animal, and permanent environment. A total of 45,425 single nucleotide polymorphisms were used in the genomic analyses. Animals genotyped with low-density chips were imputed to the required number of single nucleotide polymorphisms. All analyses were based on the single-step genomic BLUP, a method that combines phenotype, pedigree, and genotype information. Predicted transmitting abilities were expressed in percentage points as a difference from the average estimated probability of a disorder in the base population. Reliabilities of breeding values were obtained by approximation based on partitioning of a function of reliability into contributions from records, pedigree, and genotypes. Reliabilities of genomic predicted transmitting abilities for young genotyped and pedigreed females without recorded health events had average values between 50.2% (displaced abomasum) and 51.9% (mastitis). Genomic predictions for wellness traits can provide new information about an animal's genetic potential for health and new selection tools for dairy wellness improvement.


Energy landscape of a simple model for strong liquids.
We calculate the statistical properties of the energy landscape of a minimal model for strong network-forming liquids. Dynamic and thermodynamic properties of this model can be computed with arbitrary precision even at low temperatures. A degenerate disordered ground state and logarithmic statistics for the local minima energy distribution are the landscape signatures of strong liquid behavior. Differences from fragile liquid properties are attributed to the presence of a discrete energy scale, provided by the particle bonds, and to the intrinsic degeneracy of topologically disordered networks.


10 W injection-locked single-frequency continuous-wave titanium:sapphire laser.
High-power tunable lasers with good longitudinal and transverse modes are fundamental tools for exploring quantum physics. Here we report a high-power continuous-wave injection-locked titanium:sapphire laser with a low-loss cavity configuration, where only a laser crystal was installed in the laser cavity. Although the transverse mode was affected by a thermal lens formed in the laser crystal, the focal length of the thermal lens could be shifted via the temperature of the laser crystal holder or the pump power. As a result, we found a condition that 10 W single-frequency oscillation with a good transverse mode and a slope efficiency of 51% were achieved.


A user's manual for the IOM's 'Quality Chasm' report.
Fifteen months after releasing its report on patient safety (To Err Is Human), the Institute of Medicine released Crossing the Quality Chasm. Although less sensational than the patient safety report, the Quality Chasm report is more comprehensive and, in the long run, more important. It calls for improvements in six dimensions of health care performance: safety, effectiveness, patient-centeredness, timeliness, efficiency, and equity; and it asserts that those improvements cannot be achieved within the constraints of the existing system of care. It provides a rationale and a framework for the redesign of the U.S. health care system at four levels: patients' experiences; the "microsystems" that actually give care; the organizations that house and support microsystems; and the environment of laws, rules, payment, accreditation, and professional training that shape organizational action.


Characterization of vacuolar membrane proteins changed in rice root treated with gibberellin.
Rice vacuolar membrane proteins changed by gibberellin (GA) were analyzed using a proteome approach. Vacuolar membrane fractions were isolated using a discontinuous sucrose/sorbitol system and 10 proteins increased in vacuolar membrane of the root, treated with GA(3) as compared with control. Fructose-1,6-bisphosphate aldolase C-1 and vacuolar H(+)-ATPase (V-ATPase) increased in root vacuolar membrane by GA(3) interacted in rice roots. It suggests that aldolase C-1 regulates the V-ATPase mediated control of cell elongation that determines root growth.


Depressive symptomatology and pineal epidermoid cyst: a case report.
Introduction Intracranial epidermoid cysts are congenital cysts. They comprise 0.2-1.8% of primary intracranial tumours and are four to nine times as common as dermoid cysts. Case report We here in present the case of a 32-year-old man who reported sudden onset of symptoms of a depressive symptomatology and particularly severe headache, accompanied by fatigue, depressed mood most of the day, marked diminished interest or pleasure in all or almost all activities, insomnia and diminished ability to think or concentrate. Brain magnetic resolution imaging examination revealed a pineal epidermoid cystic lesion, visualised in the posterior part of the third ventricle, with a maximum diameter of ∼2.8 cm and obstructing the aqueduct of Sylvius, causing obstructive hydrocephalus. Discussion Pineal cysts may enlarge over time, because of either increased cyst fluid or intracystic haemorrhage, and become symptomatic. Brain radiological investigations in patients with depressive symptomatology may be substantial.


Smooth pursuit and saccades to moving targets in blind hemifields. A comparison of medial occipital, lateral occipital and optic radiation lesions.
We tested smooth pursuit and saccades to targets within the contralateral homonymous visual field defects of 10 patients with unilateral cerebral hemispheric lesions. Four patients had medial occipital lesions that spared the putative motion area in lateral occipitotemporal cortex and the optic radiations proximal to this site. The other six had lesions involving this area or the proximal optic radiations. From current hypotheses, that surviving extra-striate cortex is responsible for 'blindsight', we expected that the patients with lesions restricted to medial occipital cortex would be more likely to have residual ocular motor responses to moving targets. We found, however, that these patients with sparing of the lateral motion area did not show significantly better correlations of either post-saccadic eye velocity with target velocity or initial saccadic amplitude with the position of the moving target, compared with the other six patients. With increased target velocities against a background of darkness, two patients had weakly positive ocular motor correlations. However, in one patient this finding was replicated by a normal control stimulating the patient's scotoma and, in the other patient, the correlation disappeared when the eye with a residual monocular temporal crescents was occluded. These features indicate an artifact from light scatter. Only one other patient demonstrated a consistent, but weak, correlation of ocular tracking with target motion in the blind region; paradoxically, this patient had a lateral occipitotemporal lesion. We conclude that sparing of the lateral motion area is not sufficient condition for residual tracking of moving targets in homonymous visual field defects, and may not even be necessary.


[Advanced Nursing Practice in Great Britain - a personal report].
This article aims to provide an insight into the role as an Advanced Nurse Practitioner in Thoracic Surgery employed within the United Kingdom's National Health Service (NHS). Day-to-day duties were comprised of 7 Domains of Competence namely: management of patient's health status, nurse-patient relationship, teaching and coaching, professional role, managing and negotiating the health care delivery service, quality management, and cultural competence. These elements were enhanced further by becoming an independent and supplementary nurse prescriber, which helped to augment a seamless service delivery. The role formed an integral part in ensuring multi-disciplinary team cohesion and dynamics as well as the provision of continuity of care for both patients' and their families, across all health care settings.


Pilot study of sirolimus in patients with PIK3CA mutant/amplified refractory solid cancer.
In patients with refractory cancer, the effect of additional chemotherapy is very limited. Targeted agents for molecular pathways associated with cancer cell progression and survival have emerged as attractive options in several cancer types. The current pilot study assessed the efficacy and safety of sirolimus in patients with refractory cancer with PIK3CA mutation/amplification. Refractory cancer patients with PIK3CA mutation/amplification were enrolled, irrespective of tumor-types. Enrolled patients received a daily dose of 1 mg sirolimus and one cycle defined as 28 days. An assessment of the efficacy and safety of sirolimus was performed. Overall, 4 patients were enrolled between October 2014 and April 2015. The median of 2.5 cycles of sirolimus was administered. Three patients had advanced gastric cancer and one had advanced cholangiocarcinoma. The overall response rate was 0%, three patients (75%) had stable disease following one cycle and one patient (25%) received sirolimus for 4 cycles without disease progression. The median progression free survival was 1.9 months [95% confidence interval (CI), 0.3-3.5 months], and the median overall survival was 3.6 months (95% CI, 0.4-6.8 months). Grade 3 or greater hematologic/non-hematologic toxicity was not observed. Grade 1 nausea was reported in one patient each. There were no treatment-associated mortalities. Sirolimus had modest efficacy and a tolerable toxicity-profile in patients with refractory cancer with PIK3CA mutation/amplification.


Human genome editing in clinical applications: Japanese lay and expert attitudes.
Background: The world's first gene-edited babies, reported by the Chinese scientist He Jiankui, prompted an outcry of criticism and concerns worldwide over the use of genome editing for reproductive purposes. Many countries and academic associations opposed to heritable genome editing (HGE) called for public discussion involving various stakeholders. To hold a discussion of this nature and form a consensus concerning HGE, we must understand under what conditions stakeholders consider HGE acceptable and the reasons for which they deem it unacceptable. Methods: Laypeople and researchers were surveyed in May 2019. They were asked about the degree of their acceptance toward somatic genome editing (SGE) and HGE; those who answered "acceptable depending on the purpose" were queried further regarding their acceptance in the contexts of specific clinical purposes. Results: Responses were obtained from 4,424 laypeople and 98 researchers. The percentage of respondents choosing each option in attitudes to HGE was, from largest to smallest: "acceptable depending on purpose" (laypeople 49.3%; researchers 56.1%), "not acceptable for any purpose" (laypeople 45.8%; researchers 40.8%), and "acceptable for any purpose" (laypeople 5.0%; researchers 3.1%). In an additional question for those who answered "acceptable depending on the purpose," laypeople found the following purposes acceptable: infertility treatment (54.5%), treatment of life-threatening diseases (52.2%), and treatment of debilitating diseases (51.4%). Meanwhile, the degree of acceptance for enhancement purposes was 10.7, 7.9, 6.2, and 5.5% for physical, cognitive, health, and personality enhancements, respectively. In contrast, acceptance among the researchers was 94.5% and 92.7% for the treatment of life-threatening and debilitating diseases, respectively, compared with 69.1% for infertility treatment. Researchers' acceptance for enhancement purposes was similar to that of the lay participants, with 12.7, 9.1, 10.9, and 5.5% for physical, cognitive, health, and personality enhancement, respectively. Conclusion: In the past, debates regarding the acceptability of human genome editing in clinical applications tend to focus on HGE in many countries. Society will now need to debate the acceptability of both types of human genome editing, HGE and SGE.


Characterization of Tfrc-mutant mice with microcytic phenotypes.
To identify novel regulators of erythropoiesis, we performed independent forward genetic screens using the chemical mutagen ENU in mice. Among progeny displaying microcytic red-cell phenotypes, 7 independent mouse strains harboring mutations within the transferrin receptor gene Tfrc were identified. Six of the mutants, including the previously described red blood cell 6 (RBC6) strain, displayed reduced erythroblast CD71 expression and midgestation lethality of homozygotes (E12.5-E14.5), and 1 novel strain, RBC21, displayed a variable phenotype with sustained CD71 expression and late homozygous lethality (E18.5). Standard iron studies were normal in the RBC21 mutant, but intracellular ferritin was significantly reduced. The microcytic phenotype seen in the RBC21 strain was the result of impaired binding of transferrin to the receptor. Neither RBC6 nor RBC21 responded to iron replacement therapy. These studies describe how point mutations of the transferrin receptor can cause a microcytic anemia that does not respond to iron therapy and would not be detected by routine iron studies, such as serum ferritin.


Environmental exposures are important risk factors for advanced liver fibrosis in African American adults.
The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States. Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase. The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8-1.9) to 3.5 million (95% CI 2.8-4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44-3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95-5.43) but did not include diabetes (OR 0.88; 95% CI 0.61-1.27; p =0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons. The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed. Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.


Term delivery of a complete hydatidiform mole with a coexisting living fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease.
A twin pregnancy consisting of a complete hydatidiform mole with a coexisting normal fetus is extremely rare with an incidence of 1/22,000 to 1/100,000. The incidence of preterm delivery is high and few pregnancies reach near term with a viable fetus. A 34-year-old woman presented at 20 weeks of gestation with increased levels of serum beta human chorionic gonadotropin (beta-HCG) at 4.74 multiples of the median (310277.7 mIU/mL). Ultrasonography showed a hydatidiform mole together with a normal fetus. Fetal karyotyping revealed 46XY. The serum beta-HCG levels were followed up throughout the remainder of the pregnancy. A male infant weighting 2260 g and the molar tissue were delivered at 37 weeks of gestation. The karyotype of the molar tissue showed 46XX and the histopathological report confirmed our diagnosis. At 4 months postpartum, metastatic gestational trophoblastic disease of the lung was diagnosed in the mother by a computed tomography scan due to increased beta-HCG levels. The patient received three unsuccessful cycles of methotrexate and folinate. Another four cycles of chemotherapy consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) were initiated and the beta-HCG levels returned to normal. There was no evidence of recurrence in the subsequent 5 years of regular follow up. A pregnancy with a complete hydatidiform mole and a living cotwin can be a serious threat to the health of both the mother and the fetus. Early diagnosis depends on a combination of detecting an unusually high level of serum beta-HCG and ultrasound examination. We suggest that continuation of the pregnancy may be an acceptable option and that the pregnancy may continue until term if a normal fetal anatomy is assured and maternal complications are under control. Patients require careful postpartum follow up and any recurrent disease should be managed aggressively.


Arteriovenous fistulae of the internal iliac vessels.
Seven patients with arteriovenous fistulae of the internal iliac artery are reported. Ages varied from 6 to 50 years (mean 32 years). Cutaneous angiomata , leg oedema and pain was present in 4 cases each, bleeding in 2 cases whilst only one was asymptomatic. Only 1 patient had cardiac insufficiency. In six patients the lesion was a congenital malformation but in one it was posttraumatic. Arteriography both global and selective, intravenous pyelography and cardiac output are routine. Recently, pelvic computerised tomography has been most helpful. Embolization is recommended in all cases with surgery within 24 hours unless the lesion is very extensive and considered to be inoperable. Repeat embolization is used for recurrence or very extensive lesions. Results were good in five patients; in two patients the results were clinically good but control angiograms showed a recurrence.


[Experiences during training of a group for tasting bovine meat at an industrial refrigerated abattoir in Venezuela].
During three months, a group of people (meat consumers and active personnel) of a Venezuelan packing house were asked to assign discretionary scores to a sample of 103 beef longissimus steaks in order to familiarize them with the score sheet and to their future job as panelists. Scores assigned to 37 steaks by seven candidates that assisted regularly to these preliminary sessions (out of 12 attendants), were subjected to Analysis of Variance (ANOVA) to determine variability among judges before training. The whole group (n = 12) potential candidates from both sexes, and ranging between 25 and 45 years, were interviewed and pre selected for formal training. Triangle tests were used as selection tool and allowed for dismissing two of them. Training reinforced acquaintance with test procedures and improved natural abilities, sensitivity and memory for test attributes by using an 8-point descriptive scale to describe samples differing in fiber tenderness, amount of connective tissue, overall tenderness, juiciness, and flavor intensity. After 2 mo. of training (5 h weekly) the first panel performance evaluation (PPE) was conducted over 4 days with 3 sessions per day and 3 samples per session with 9 different samples. Data for each candidate were subjected to one-way ANOVA and F-ratio served as criteria to rank candidates' ability for describing each attribute. Panelist 7 and 8 rated last and were excused to conform an 8-member panel. The panel evaluated 300 samples during a 6-mo period and a second PPE was conducted. The second PPE revealed changes in relative ranking positions. Data from the first 40 (out of 300) samples were subjected to ANOVA for testing score (panelist) variability after training. A significant effect of panelist was detected before (P < .05) and after (P < .001) training, but a much greater variability became apparent in untrained candidates. Mean separation for trained panelist only differed in decimal units within the same points or adjacent points of the scale. Results validated methodologies used for panel training and the panel capability for sensorial evaluation of non-processed beef.


The new view of hydrophobic free energy.
In the new view, hydrophobic free energy is measured by the work of solute transfer of hydrocarbon gases from vapor to aqueous solution. Reasons are given for believing that older values, measured by solute transfer from a reference solvent to water, are not quantitatively correct. The hydrophobic free energy from gas-liquid transfer is the sum of two opposing quantities, the cavity work (unfavorable) and the solute-solvent interaction energy (favorable). Values of the interaction energy have been found by simulation for linear alkanes and are used here to find the cavity work, which scales linearly with molar volume, not accessible surface area. The hydrophobic free energy is the dominant factor driving folding as judged by the heat capacity change for transfer, which agrees with values for solvating hydrocarbon gases. There is an apparent conflict with earlier values of hydrophobic free energy from studies of large-to-small mutations and an explanation is given.


Effects of starch- vs. fiber-based energy supplements during winter grazing on partitioning of fat among depots and adipose tissue gene expression in growing cattle and final carcass characteristics.
Fifty-five normal-weaned Angus steers (268 ± 22 kg; 265 ± 16 d of age) were used to evaluate the effects of starch- vs. fiber-based energy supplements for stocker cattle grazing low-quality dormant native range on growth performance, body composition, and adipose tissue development of different fat depots. Steers were randomly allotted to 4 treatments: 1.02 kg·steer(-1)·d(-1) of a 40% CP cottonseed meal-based supplement (CON), corn/soybean meal-based supplement fed at 1% of BW (CORN), soybean hull/soybean meal-based supplement fed at 1% of BW (SBH), or dried distillers grains with solubles fed at 1% of BW (DDGS). All supplements were individually fed 5 d/wk during the 121-d winter grazing phase. After winter grazing, 3 steers per treatment were harvested to determine body composition and carcass characteristics, and collect subcutaneous (SC) and perirenal (PR) adipose tissue samples. The remaining steers grazed cool-season grass pastures for 74 d without supplementation before finishing. Steers were fed a common finishing diet for 113 d before harvest, at which time carcass characteristics were collected at a commercial abattoir. Energy supplementation increased (P < 0.01) winter grazing ADG compared with CON steers, and CORN steers had greater (P < 0.01) ADG than SBH and DDGS steers. Energy supplementation increased (P < 0.04) mesenteric/omental fat mass but did not influence (P > 0.13) 12th rib fat thickness or marbling score at intermediate harvest compared with CON steers. The mRNA expression of genes involved in lipogenesis and markers of adipogenesis were greater (P < 0.05) in PR adipose tissue of energy-supplemented steers compared with CON steers but not in SC adipose tissue. Fiber-supplemented steers had greater (P < 0.01) mRNA expression of fatty acid synthase and fatty acid binding protein 4 compared with CORN steers in PR adipose tissue but not SC adipose tissue. At final harvest, energy-supplemented steers had greater (P < 0.05) KPH and yield grade than CON steers, but no differences (P = 0.75) in marbling score were observed. Neither energy supplementation nor type of energy supplement influenced intramuscular fat deposition in stocker cattle grazing dormant native range. These data suggest that the total energy intake and stage of animal maturity during grazing supplementation were not great enough to influence marbling deposition.


[Protocol for the care of acute myocardial infarction in emergency: Código infarto (The Infarction Code)].
Cardiovascular diseases are a major public health problem because of their they impact on more than 30% of all deaths worldwide. In our country and in the Instituto Mexicano del Seguro Social (IMSS) are also the leading cause of death and the main cause of lost of healthy life years due to disability or premature death. 50% of deaths are premature; most of them are due to acute myocardial infarct. However, the investment for cardiovascular health is poor and there are no comprehensive cares programs focused on the treatment of this diseases or the control of their risk factors. To address this problem, the first institutional care program was developed, called "A todo corazón", which aims to strengthen actions to promote healthy habits, prevention and care of cardiovascular diseases. The initial approach is to implement a protocol of care emergency services called "Código infarto", which is intended to ensure the diagnosis and treatment of patients demanding emergency care for acute myocardial infarction and receive reperfusion treatment with primary angioplasty in the first 90 minutes, or fibrinolytic therapy in the first 30 minutes after the admission to the IMSS emergency services.


Impact of a worker's compensation practice guideline on lumbar spine fusion in Washington State.
In the face of escalating medical costs for injured workers, the Washington State Department of Labor and Industries (L&I), which pays for most workers' compensation costs in the state, established guidelines for elective lumbar fusion as part of its inpatient utilization review program. The guidelines were tied to reimbursement strictures. The authors attempt to assess the effects of these guidelines, which were introduced in November 1988, upon subsequent L&I fusion procedures. Discharge data from the Comprehensive Hospital Abstract Reporting System and algorithms using International Classification of Diseases, Version 9, Clinical Modification diagnosis and procedure codes were used to identify lumbar surgical cases. Population estimates were from the 1990 US Census Bureau. During the period of years 1987 through 1992, the lumbar fusion rate for the state showed a 26% decline compared with a 3% decrease for all lumbar operations. After November 1988, when the guidelines went into effect, the state fusion rate declined 33%, whereas rates for nonfusion operations essentially were unchanged. The sharpest decline corresponded in time to implementation of the guidelines. Prior to the initiation of L&I guidelines, the proportion of fusions among L&I patients was higher than among non-L&I patients. The opposite was true by the end of 1992, and the L&I proportion decreased more rapidly than the non-L&I proportion. Time series analysis revealed that both the decline in Washington state lumbar fusion rates and the decline in the proportion of lumbar fusion among L&I patients were statistically significant. The data suggest that the L&I lumbar fusion surgery criteria and reimbursement standards implemented in 1988 contributed to a decline in rates of performing that procedure. The utilization review aspect of the guidelines as well as the process of involving surgeons in the preparation and dissemination of guidelines also may have been contributory.


An improved method to determine the onset timings of reflections in an acoustic impulse response.
Determining the absolute onset time of reflections in an acoustic impulse response (IR) has applications for both subjective and physical acoustics problems. Although computationally simple, a first-order energetic analysis of the IR can lead to false-positive identification of reflections. This letter reports on a method to determine reflection onset timings using a modified running local kurtosis analysis to identify regions in the IR where the distribution is non-normal. IRs from both real and virtual rooms are used to validate the method and to find optimum analysis window sizes.


A unique activation-promotion mechanism of the influenza B M2 proton channel uncovered by multiscale simulations.
The influenza B M2 protein (BM2) forms an acid-activated proton channel that is important for the virus's lifecycle. Despite extensive research efforts, the detailed activation mechanism of the BM2 proton channel is often elusive. Herein a pH-regulated mechanism of the BM2TM domain has been systematically characterized using multiscale computer simulations, including classical molecular dynamics, constant pH molecular dynamics (CpHMD) and quantum mechanics/molecular mechanics (QM/MM) approaches. Our simulations reveal a pH-dependent conformational switch from the C-terminal closed to the C-terminal open conformers, and provide the free energy of conformational activation coupled to the titration of the His19 tetrad. Importantly, our results confirm the coupling titration between the His19 tetrad and His27 tetrad, and identify that the full-cationic state (His2744+) dominates at the low pH (the His19 tetrad at +2, +3 and +4 charge states). Our QM/MM simulations indicate that the second titratable histidine, His27, could further promote the BM2 acid activation and speed up proton dissociation from the HxxxW motif, thus facilitating proton conduction by BM2. Taken together, a unique "activation-promotion mechanism" about the BM2 proton channel is proposed, and these results may be helpful for the understanding of other similar proton channels and the development of BM2 inhibitors.


HSP47 and FKBP65 cooperate in the synthesis of type I procollagen.
Osteogenesis imperfecta (OI) is a genetic disorder that results in low bone mineral density and brittle bones. Most cases result from dominant mutations in the type I procollagen genes, but mutations in a growing number of genes have been identified that produce autosomal recessive forms of the disease. Among these include mutations in the genes SERPINH1 and FKBP10, which encode the type I procollagen chaperones HSP47 and FKBP65, respectively, and predominantly produce a moderately severe form of OI. Little is known about the biochemical consequences of the mutations and how they produce OI. We have identified a new OI mutation in SERPINH1 that results in destabilization and mislocalization of HSP47 and secondarily has similar effects on FKBP65. We found evidence that HSP47 and FKBP65 act cooperatively during posttranslational maturation of type I procollagen and that FKBP65 and HSP47 but fail to properly interact in mutant HSP47 cells. These results thus reveal a common cellular pathway in cases of OI caused by HSP47 and FKBP65 deficiency.


Preparation, properties and applications of nanocellulosic materials.
Recently, nano materials derived from natural renewable resources have drawn much attention in the nanotechnology research thrust. Lignocelluloses are composed of cellulosic nano-fibrils which can be disintegrated by chemical, mechanical and enzymatic methods in order to obtain nanocellulose. Further, nanocellulose can also be synthesized by bacterial method in a suitable culture. Nanocelluloses have many interesting properties (viz. nano-dimension, renewability, low toxicity, biocompatibility, bio-degradability, easy availability and low cost) which make them ideal nanomaterials for diverse applications. In this paper, author reviewed researches on recent advances in nanocellulosic materials. Various methods of nanocellulose preparation and their properties, surface modifications of nanocellulose, and applications of nanocellulose in the diverse fields have been discussed in the paper.


Pressure threshold for inhibition of dense granular film opening.
Controlling the stability of a granular film is essential in a wide range of industrial applications, from aerated building materials to recovering ore by flotation and treating wastewater. We therefore carry out experiments of granular film opening where particles of hundred of micrometers above random close packing zip the two interfaces of a soap film which liquid pressure is controlled. We create a hole at the center of this dense granular film and, surprisingly, we observe that the opening is not always inhibited. Different behaviours are identified: total bursting of the granular film, intermittent opening and jammed state for which the hole does not evolve. The liquid pressure drives the transition from one opening behaviour to another. Lower is the liquid pressure, more jammed is the system. The critical pressure transition scales as the surface tension over the particle size until the finite size of the granular film is only few tens of the particle size. Ultimately we evidence that spontaneous hole in thin film between particle do not lead to the granular film failure.


Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy.
Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM. To delineate contributions of the epicardium to the pathogenesis of ACM, the Dsp allele was conditionally deleted in the epicardial cells in mice upon expression of tamoxifen-inducible Cre from the Wt1 locus. Wild type (WT) and Wt1-CreERT2:DspW/F were crossed to Rosa26mT/mG (R26mT/mG) dual reporter mice to tag the epicardial-derived cells with the EGFP (enhanced green fluorescent protein) reporter protein. Tagged epicardial-derived cells from adult Wt1-CreERT2:R26mT/mG and Wt1-CreERT2: R26mT/mG:DspW/F mouse hearts were isolated by fluorescence-activated cell staining and sequenced by single-cell RNA sequencing. WT1 (Wilms tumor 1) expression was progressively restricted postnatally and was exclusive to the epicardium by postnatal day 21. Expression of Dsp was reduced in the epicardial cells but not in cardiac myocytes in the Wt1-CreERT2:DspW/F mice. The Wt1-CreERT2:DspW/F mice exhibited premature death, cardiac dysfunction, arrhythmias, myocardial fibro-adipogenesis, and apoptosis. Single-cell RNA sequencing of ≈18 000 EGFP-tagged epicardial-derived cells identified genotype-independent clusters of endothelial cells, fibroblasts, epithelial cells, and a very small cluster of cardiac myocytes, which were confirmed on coimmunofluorescence staining of the myocardial sections. Differentially expressed genes between the paired clusters in the 2 genotypes predicted activation of the inflammatory and mitotic pathways-including the TGFβ1 (transforming growth factor β1) and fibroblast growth factors-in the epicardial-derived fibroblast and epithelial clusters, but predicted their suppression in the endothelial cell cluster. The findings were corroborated by analysis of gene expression in the pooled RNA-sequencing data, which identified predominant dysregulation of genes involved in epithelial-mesenchymal transition, and dysregulation of 146 genes encoding the secreted proteins (secretome), including genes in the TGFβ1 pathway. Activation of the TGFβ1 and its colocalization with fibrosis in the Wt1-CreERT2:R26mT/mG:DspW/F mouse heart was validated by complementary methods. Epicardial-derived cardiac fibroblasts and epithelial cells express paracrine factors, including TGFβ1 and fibroblast growth factors, which mediate epithelial-mesenchymal transition, and contribute to the pathogenesis of myocardial fibrosis, apoptosis, arrhythmias, and cardiac dysfunction in a mouse model of ACM. The findings uncover contributions of the epicardial-derived cells to the pathogenesis of ACM.


Comparison of knee mechanics among risky athletic motions for noncontact anterior cruciate ligament injury.
It has been suggested that noncontact anterior cruciate ligament injury commonly occurs during sports requiring acute deceleration or landing motion and that female athletes are more likely to sustain the injury than male athletes. The purpose of this study was to make task-to-task and male-female comparisons of knee kinematics and kinetics in several athletic activities. Three-dimensional knee kinematics and kinetics were investigated in 20 recreational athletes (10 males, 10 females) while performing hopping, cutting, turning, and sidestep and running (sharp deceleration associated with a change of direction). Knee kinematics and kinetics were compared among the four athletic tasks and between sexes. Subjects exhibited significantly lower peak flexion angle and higher peak extension moment in hopping compared with other activities (P < .05). In the frontal plane, peak abduction angle and peak adduction moment in cutting, turning, and sidestep and running were significantly greater compared with hopping (P < .05). No differences in knee kinematics and kinetics were apparent between male and female subjects. Recreational athletes exhibited different knee kinematics and kinetics in the four athletic motions, particularly in the sagittal and frontal planes. Male and female subjects demonstrated similar knee motions during the four athletic activities.


Hepatic bile duct hamartomas (von Meyenburg Complexes): MR and MR cholangiography findings.
Multiple bile duct hamartomas (MBDHs) of the liver, also known as von Meyenburg complexes, are easily confused with diffuse metastatic disease of the liver on US and CT. At present, histologic examination after tissue preevaluation is usually necessary for definite diagnosis. We report four cases in which the MR features, and especially the MR cholangiographic (MRC) findings, were highly suggestive for MBDH. Characteristic findings include multiple markedly hyperintense nodules on T2-weighted imaging, typically measuring <1.5 cm; no communication with the biliary tree; and irregular delineation of the lesions with no or slight rim enhancement following gadolinium administration.


[INTEGRATED APPROACH TO PREVENT FUNCTIONAL DECLINE IN HOSPITALIZED ELDERLY].
Hospital related functional decline in older patients is an underestimated problem. Thirty-five procent of 70-year old patients experience functional decline during hospital admission in comparison with pre-illness baseline. This percentage increases considerably with age. To address this issue, the Vlietland Ziekenhuis in The Netherlands has implemented the Prevention and Reactivation Care Programme (PReCaP), an innovative program aimed at reducing hospital related functional decline among elderly patients by offering interventions that are multidisciplinary, integrated and goal-oriented at the physical, social, and psychological domains of functional decline. This paper presents a detailed description of the intervention, which incorporates five distinctive elements: (1) Early identification of elderly patients with a high risk of functional decline, and if necessary followed by the start of the reactivation treatment within 48 h after hospital admission; (2) Intensive follow-up treatment for a selected patient group at the prevention and Reactivation Centre; (3) Availability of multidisciplinary geriatric expertise; (4) Provision of support and consultation of relevant professionals to informal caregivers; (5) Intensive follow-up throughout the entire chain of care by a casemanager with geriatric expertise. Outcome and process evaluations are ongoing and results will be published in a series of forthcoming papers. This article is an edited translation of the previously published article 'Integrated approach to prevent functional decline in hospitalized elderly: the Prevention and Reactivation Care Program (PReCaP), BMC Geriatrics 2012;12:7, AJBM de Vos, KJE Asmus-Szepesi, TJEM Bakker, PL de Vreede, JDH van Wijngaarden, EW Steyerberg, JP Mackenbach, AP Nieboer.


Comparison of sufentanil-nitrous oxide anaesthesia with fentanyl-nitrous oxide anaesthesia in geriatric patients undergoing major abdominal surgery.
We have measured haemodynamic changes and plasma concentrations of catecholamines during sufentanil-nitrous oxide and fentanyl-nitrous oxide anaesthesia in a controlled, randomized, double-blind study of 20 geriatric patients (age 65-86 yr) undergoing major abdominal surgery. Fentanyl 7 micrograms kg-1 followed by infusion of 3 micrograms kg-1 h-1 was compared with sufentanil 1 micrograms kg-1 followed by 0.4 micrograms kg-1 h-1. The opioid was supplemented with 60-67% nitrous oxide in oxygen. Haemodynamic changes, plasma concentrations of catecholamines (by high pressure liquid chromatography) and opioids (by radioimmunoassay), and myocardial lactate extraction were measured in the awake state, and at defined times during anaesthesia and surgery. Haemodynamic state was stable during induction and tracheal intubation in both groups, while during stressful operative periods there were increases in mean arterial pressure (17% in the fentanyl group; 11% in the sufentanil group), heart rate (fentanyl 20%, sufentanil 14%) and plasma concentrations of catecholamines (adrenaline: fentanyl 316%, sufentanil 86%; noradrenaline: fentanyl 78%, sufentanil 186%) in both groups. Sufentanil was similar to fentanyl in attenuating the haemodynamic and hormonal responses to surgical stimulation. In two patients in the fentanyl group and three in the sufentanil group, myocardial lactate production was observed temporarily, indicating myocardial ischaemia caused by surgical stress.


Five phylogenetically close rice SWEET genes confer TAL effector-mediated susceptibility to Xanthomonas oryzae pv. oryzae.
Bacterial plant-pathogenic Xanthomonas strains translocate transcription activator-like (TAL) effectors into plant cells to function as specific transcription factors. Only a few plant target genes of TAL effectors have been identified, so far. Three plant SWEET genes encoding putative sugar transporters are known to be induced by TAL effectors from rice-pathogenic Xanthomonas oryzae pv. oryzae (Xoo). We predict and validate that expression of OsSWEET14 is induced by a novel TAL effector, Tal5, from an African Xoo strain. Artificial TAL effectors (ArtTALs) were constructed to individually target 20 SWEET orthologs in rice. They were used as designer virulence factors to study which rice SWEET genes can support Xoo virulence. The Tal5 target box differs from those of the already known TAL effectors TalC, AvrXa7 and PthXo3, which also induce expression of OsSWEET14, suggesting evolutionary convergence on key targets. ArtTALs efficiently complemented an Xoo talC mutant, demonstrating that specific induction of OsSWEET14 is the key target of TalC. ArtTALs that specifically target individual members of the rice SWEET family revealed three known and two novel SWEET genes to support bacterial virulence. Our results demonstrate that five phylogenetically close SWEET proteins, which presumably act as sucrose transporters, can support Xoo virulence.


Progressive utterance-final lengthening in syllables with final fricatives.
The generality of the pattern of progressively greater lengthening within the utterance-final syllable, previously found with respect to final stops, is shown to extend to syllables in Hebrew with final fricatives. Seven native speakers of Hebrew read matched sentence pairs in which bisyllabic key words appeared in non-final and sentence-final position. Final fricatives showed almost four times as much utterance-final lengthening as the preceding stressed vowel. Final lengthening affected the duration of each segment of the final syllable, and also extended to the initial unstressed syllable of the final word. Though final fricatives showed more lengthening in sentence-final position than final-stop closures, no difference was found in the lengthening of the vowels preceding these consonants. The greater lengthening of the final fricative relative to the preceding vowel resulted in C/V ratios which failed to distinguish between the voiceless fricative in non-final position and the voiced fricative in utterance-final position. These results suggest that sentence position is taken into account in the perception of voicing, such that the C/V ratio applicable in non-final position is increased by a factor of two in final position.


Two separate nodules of Merkel cell carcinoma occurring concomitantly on one cheek.
Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroectodermal carcinoma arising from mechanoreceptor Merkel cells. Multiple MCCs are even rarer. We report a case of two independent MCCs simultaneously present in the cheek of a patient, which were effectively and esthetically treated using a cheek flap. Punch biopsy performed in a 60-year-old woman admitted with a chief complaint of two skin-colored hard nodules in her left cheek, accompanied by an itching sensation, was suggestive of MCC. Accordingly, we performed sentinel lymph node biopsy through the modified Blair incision under general anesthesia, in cooperation with the head and neck surgery department. The defect was covered with a cheek flap by slightly extending the existing incision following wide excision with a safety margin of 1 cm. This paper is significant in that it introduces an effective reconstruction technique that maintains function using a cheek flap for the management of this rare case. In addition, this paper is the first to classify multiple MCCs according to the time of onset. We believe that this paper presents an effective alternative reconstruction technique with sentinel node biopsy through the modified Blair incision.


A COMPARATIVE ANALYSIS OF THE ECOLOGICAL SIGNIFICANCE OF MAXIMAL LOCOMOTOR PERFORMANCE IN CARIBBEAN ANOLIS LIZARDS.
We examined the sprinting and jumping capabilities of eight West Indian Anolis species during three natural activities (escape from a predator, feeding, and undisturbed activity). We then compared these field data with maximal performance under optimal laboratory conditions to answer three questions: (1) Has maximal (i.e., laboratory) sprinting and jumping performance coevolved with field performance among species? (2) What proportion of their maximum capabilities do anoles sprint and jump in different ecological contexts? (3) Does a relationship exist between maximal sprinting and jumping ability and the proportion of maximal performance used in these contexts? Among species, maximal speed is tightly positively correlated with sprinting performance during both feeding and escape in the field. Sprinting speed during escape closely matches maximal sprinting ability (i.e., about 90% of maximum performance). By contrast, sprinting performance during undisturbed activity is markedly lower (about 32% of maximum) than maximal sprinting performance. Sprinting ability during feeding is intermediate (about 71% of maximum) between field escape and field undisturbed activity. In contrast to sprinting ability, jumping ability is always substantially less than maximum (about 40% of maximum during feeding and undisturbed activity). A negative relationship exists among species between maximal speed and the proportion to which species sprint to their maximal abilities during field escape.


Posterior reversible encephalopathy syndrome secondary to asymptomatic poststreptococcal glomerulonephritis in a child with sickle cell anemia: a case report.
Posterior reversible encephalopathy syndrome is a neurotoxic condition that occurs as a result of the failure of posterior circulatory autoregulation in response to acute changes in blood pressure. Overperfusion with resultant disruption of the blood-brain barrier results in vasogenic edema, but not infarction. Posterior reversible encephalopathy syndrome can be the presenting feature of postinfectious glomerulonephritis, which has been reported in approximately 5% of hospitalized children, and it has been reported in very few cases of adult patients with sickle cell anemia. We report a very rare case of posterior reversible encephalopathy syndrome that occurred in a child with sickle cell anemia. This presentation should be differentiated from other neurologic manifestations that occur in patients with sickle cell anemia, because management is totally different. We report what is to our knowledge the first reported case of a 9-year-old Saudi girl with sickle cell anemia who developed posterior reversible encephalopathy syndrome secondary to asymptomatic poststreptococcal glomerulonephritis. This occurred after full recovery from acute chest syndrome and severe vaso-occlusive crisis. The purpose of this report is to emphasize that all efforts should be made to explore the causes of different neurologic manifestations that occur in patients with sickle cell anemia, because this will require different pathways of management.


Photocatalytic Modular Cyanoalkylamination of Alkenes Involving Two Different Iminyl Radicals.
The modular cyanoalkylamination of alkenes using bench-stable and easy-to-handle α-imino-oxy acid oxime esters as difunctional reagents creates new synthetic avenues. A metal-free photosensitization protocol for the installation of both amino and cyanoalkyl functionalities onto alkene feedstocks in a single step via two differently reactive nitrogen-centered radicals was developed via energy-transfer catalysis. Excellent functional group tolerance and mild reaction conditions also render this protocol suitable for the cyanoalkylamination of pharmaceutically relevant molecule-derived alkenes.


To Give or Not to Give? Prescribing Antibiotics to the Tonsillectomy Patients in a Tertiary Care Setting.
Introduction Adeno-tonsillectomy is one of the most common procedures performed worldwide in pediatric age group. Antibiotics use after tonsillectomy is like any other surgical procedure; and it is thought that the antibiotic use may help to reduce post-operative morbidity. Giving antibiotics in tonsillectomy patients is a common practice for decades but recently there has been a paradigm shift towards not using the antibiotics, especially in the pediatric population. Methods A prospective study was done on a cohort of 123 patients and they were divided into two groups on the basis of choice to receive or not to receive antibiotics after tonsillectomy, and these patients were followed in post-operative period to see any differences in the rate of complications. Results No significant statistical correlation was found between age, gender or post-operative visits and post-operative complications in between the two groups. Half of the patients received antibiotics; however, the use of antibiotics did not show a significant decrease in post-operative complications. Conclusion Regular use of antibiotics in post-tonsillectomy patients should not be advised as the use of antibiotics do not prevent or reduce post-operative complications in tonsillectomy patients.


Calcification in the portal vein wall.
Calcification in the portal vein is a rare radiologic finding, occurring almost always in patients with portal hypertension. Calcium may be deposited in a thrombus or, as in this patient, in the vein wall. The characteristic position, location, and pattern of portal vein wall calcification permit its diagnosis from radiographs of the abdomen.


Otomycosis in the South of Iran with a High Prevalence of Tympanic Membrane Perforation: A Hospital-Based Study.
Otomycosis is a superficial infection of the external ear caused by fungal pathogens. The genera Aspergillus and Candida are considered the main fungal causative agents, with the predominance of Aspergillus section Nigri. The present study aimed to evaluate the clinical symptoms of patients with otomycosis and predisposing factors and to identify fungal etiological agents using molecular approaches. We also present an overview of published papers on tympanic membrane perforation (TMP) secondary to otomycosis. An otorhinolaryngologist collected specimens from external ear canals of patients with suspected otomycosis based on the patient's history and clinical examinations. The specimens were collected using sterile swabs. Fungal isolates were confirmed in clinical specimens by direct microscopy and culture methods. Fungal isolates were identified based on molecular approaches. In total, specimens from 211 patients with suspected otomycosis were examined. The presence of fungi was confirmed in about 51% of patients based on fungal elements in direct microscopy and culture-positive fungi. Aspergillus tubingensis was the most commonly isolated species (52.77%), followed by Aspergillus niger (25.92%). Otomycosis due to infection with Candida species was observed in 16% of cases. Of note, in 36.11% of cases, otomycosis was associated with TMP. A mycological examination is indispensable for a correct diagnosis in patients with otitis extern. TMP should be considered in patients with otomycosis, as it appears to be relatively common in this population.


Radiographic evaluation of the prevalence and technical quality of root canal treatment in a French subpopulation.
This study was undertaken to examine the prevalence and technical quality of root fillings and the periapical status of endodontically treated teeth in a French subpopulation. Full-mouth periapical radiographs were obtained from 208 consecutive adult patients seeking care within the dental service provided by the Hôtel-Dieu in Paris. The occurrence and technical quality of root fillings were assessed for each root according to the position and the density of the obturation. The periapical status was evaluated using the Periapical Index Scoring System. The type of coronal restoration and the presence of posts were also noted. Of the 8743 roots included in the survey, 23% were root-filled. An acceptable standard of treatment was found in 21% of roots with 16% of these cases associated with signs of periapical disease. In roots with unacceptable root-fillings, 27% had periapical pathology. A post was seen in 26% of the root-filled canals, with 29% of these cases associated with periapical pathology. An intracoronal restoration existed in 30% of the filled roots, of which 22% exhibited a periapical lesion. An extra-coronal restoration was present in 60% of the filled roots, of which 24% had radiographic signs of periapical pathology. The remaining 10% of filled roots that had no coronal restoration were associated with periapical pathology in 33% of cases. At least one periapical lesion was seen in 63% of the patients. The results demonstrate a high prevalence of root-filled teeth and poor technical quality of treatment. Roots presenting with acceptable root fillings were associated with a lower prevalence of periapical pathology (P < 0.001). Posts in roots were associated with periapical pathology significantly more than in roots without posts (P < 0.001).


Expression, content, and localization of insulin-like growth factor I in human achilles tendon.
In animals insulin-like growth factor I (IGF-I) stimulates collagen production by fibroblasts and is expressed in tendons together with its binding protein 4 (IGFBP-4). However, the presence of IGF-I and IGFBP-4 in human tendon tissue is not described. Tissue IGF-I content was examined by immunoflourometric assay, real-time PCR, and immunohistochemistry used to localize and determine expression of IGF-I and IGFBP-4 in 6 postmortem human Achilles tendons. Tendon tissue concentrations of IGF-I were found to be 0.53 +/- 0.10 ng/g. Furthermore, we demonstrated that IGF-I and IGFBP-4 are localized around the tendon fibroblasts and that mRNA for IGF-I and IGFBP-4 can be determined in human tendon tissue. The present study adds support for the roles of IGF-I and IGFBP-4 in the regulation of tendon adaptive responses to mechanical loading.


Outcome and complication rate of nasal planectomy reconstructed with direct mucocutaneous apposition.
Nasal planectomy is recommended in cases of squamous cell carcinoma of the nasal planum in dogs and can be curative if excision is complete. Due to the noticeable alteration in appearance inherent in nasal planectomy, several techniques are described for reconstruction. The goal of this study is to report the complication rate and owner satisfaction following nasal planectomy with repair by direct mucocutaneous apposition compared to other reported reconstruction techniques meant to be more cosmetic. Eleven dogs were identified that underwent nasal planectomy with reconstruction via mucocutaneous apposition. Complications were noted in 8/11 dogs: all minor. All dogs underwent CT preoperatively for surgical planning. Complete excision was noted in 10/11 cases. Results suggest that direct mucocutaneous apposition is a viable surgical option for reconstruction following nasal planectomy with favorable major complication rates and owner satisfaction. In addition, direct mucocutaneous apposition for closure following nasal planectomy should be considered, especially in cases in which bone is not resected, because of low complication rates and reasonable cosmetic outcome.


Effect of combined treatment with rosuvastatin and protein kinase Cβ2 inhibitor on angiogenesis following myocardial infarction in diabetic rats.
The aim of the present study was to investigate the effects of combined treatment with rosuvastatin and LY333531, a selective protein kinase C (PKC)β2 inhibitor, on angiogenesis under hyperglycemic conditions. Human umbilical vein endothelial cells (HUVECs) cultured in medium containing a normal or high concentration of glucose (33.3 mmol/l) were treated with rosuvastatin (0.1 µmol/l) alone or in combination with LY333531 (10 nmol/l). HUVEC migration and tube formation were assessed. Furthermore, rats with streptozotocin-induced diabetes were randomly divided into groups and treated with either rosuvastatin alone (5 mg/kg/day) or in combination with LY333531 (10 mg/kg/day) for 4 weeks following the induction of myocardial infarction (MI). Echocardiographic patterns, the extent of myocardial fibrosis, capillary density in myocardial tissue, the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), as well as the expression levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF‑1α) were assessed. The results from the in vitro experiment revealed that the tube-forming and migration ability of the HUVECs exposed to high-glucose medium was significantly improved in the group treated with the combination of rosuvastatin and LY333531. In vivo, the combination of rosuvastatin and LY333531 significantly improved left ventricular function, reduced the extent of myocardial fibrosis and increased myocardial capillary density compared to treatment with rosuvastatin alone. In addition, the expression levels of VEGF, and Akt and eNOS phosphorylation were significantly higher in the group exposed to the combination treatment than in the group treated with rosuvastatin alone. The results of the present study indicate that, compared to treatment with rosuvastatin alone, combined treatment with rosuvastatin and LY333531 promotes a greater level of angiogenesis in diabetic rats with MI. This effect is likely mediated through the upregulation of the VEGF‑dependent Akt/eNOS signaling pathway.


Objective measurement of backscattered light from the anterior and posterior cornea in vivo.
To develop an objective and repeatable method of measuring corneal backscattered light from different depths of the cornea in vivo. A modified slit lamp ("scatterometer"), with a video camera and synchronous white strobe light, was used to capture images of a 0.1-mm-wide slit beam through the cornea. Image analysis software was developed to measure backscatter from digitized high-magnification images of 82 normal corneas of 41 subjects. Forty eyes of 20 of the same subjects were examined again after 1 month. Mean backscatter from the anterior, middle, and posterior thirds of the cornea was compared between repeated measurements, and expressed in arbitrary scatter units (SU). Backscatter in the anterior third of the cornea was 451 +/- 42 SU (mean +/- SD, n = 82), from the middle third was 274 +/- 29 SU (n = 82), and from the posterior third was 242 +/- 28 SU (n = 82). The difference in backscatter measured a month apart was 5 +/- 27 SU (P = 0.34), 2 +/- 17 SU (P = 0.42), and 0 +/- 15 SU (P = 0.95) in the anterior, middle, and posterior thirds of the cornea, respectively. Minimum detectable differences between measurements were 12, 8, and 7 SU in the anterior, middle and posterior thirds, respectively (alpha = 0.05, beta = 0.20, n = 40). Backscatter can be measured at different depths of the cornea from high-magnification digitized images of a narrow slit beam through the cornea. The method is objective and repeatable and can be applied in prospective studies of deep and posterior lamellar keratoplasty.


Osteoclast-like giant cell tumors of the pancreas and liver.
Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient's survival is currently more than 15 mo, making him the longest survivor with an OGCT of the liver to date.


Efficacy of the Müller Muscle-Conjunctival Resection for the Correction of Unilateral Ptosis following External Levator Operations in Patients with Bilateral Involutional Ptosis.
Patients with aponeurotic blepharoptosis who are treated with external levator advancement may experience complications such as upper eyelid height asymmetry and often require revision surgery. The authors assessed the efficacy of Müller muscle-conjunctival resection in cases with upper eyelid height asymmetry following bilateral external levator advancement. The authors used retrospective analysis of 11 cases between September of 2016 and October of 2018 with eyelid asymmetry following bilateral external levator advancement. Following a positive phenylephrine test, these patients underwent unilateral Müller muscle-conjunctival resection revision surgery to treat the undercorrected eyelid. Preoperative and postoperative marginal reflex distance 1, symmetry outcomes, and clinical outcomes of patients were evaluated after the Müller muscle-conjunctival resection. The average patient age was 54.81 ± 3.95 years (range, 37 to 69 years; median, 56 years); seven patients (63.6 percent) were women. Hering dependency was seen in all patients before the external levator advancement. A total of three patients underwent bilateral external levator advancement simultaneously, and eight patients underwent bilateral external levator advancement sequentially. The phenylephrine test was positive in all patients before the Müller muscle-conjunctival resection. Symmetry outcomes were assessed after the revision surgery as perfect (<0.5 mm), good (≥0.5 to <1 mm), or fair (≥1 mm) in four patients, six patients, and one patient, respectively. An optimal correction was noted in 13 of the 22 eyelids after the revision surgery, whereas eight of the 22 eyelids had minimal undercorrection, and one eyelid had minimal overcorrection. Müller muscle-conjunctival resection revision surgery for treatment of the ptotic eyelid following bilateral external levator advancement is viable and may represent a new alternative among the limited revision techniques. Therapeutic, IV.


Mental Health Services Utilization and Expenditures Among Children Enrolled in Employer-Sponsored Health Plans.
Mental illness in children increases the risk of developing mental health disorders in adulthood, and reduces physical and emotional well-being across the life course. The Mental Health Parity and Addiction Equity Act (MHPAEA, 2008) aimed to improve access to mental health treatment by requiring employer-sponsored health plans to include insurance coverage for behavioral health services. Investigators used IBM Watson/Truven Analytics MarketScan claims data (2007-2013) to examine: (1) the distribution of mental illness; (2) trends in utilization and out-of-pocket expenditures; and (3) the overall effect of the MHPAEA on mental health services utilization and out-of-pocket expenditures among privately-insured children aged 3 to 17 with mental health disorders. Multivariate Poisson regression and linear regression modeling techniques were used. Mental health services use for outpatient behavioral health therapy (BHT) was higher in the years after the implementation of the MHPAEA (2010-2013). Specifically, before the MHPAEA implementation, the annual total visits for BHT provided by mental health physicians were 17.1% lower and 2.5% lower for BHT by mental health professionals, compared to years when MHPAEA was in effect. Children covered by consumer-driven and high-deductible plans had significantly higher out-of-pocket expenditures for BHT compared to those enrolled PPOs. Our findings demonstrate increased mental health services use and higher out-of-pocket costs per outpatient visit after implementation of the MHPAEA. As consumer-driven and high-deductible health plans continue to grow, enrollees need to be cognizant of the impact of health insurance benefit designs on health services offered in these plans.


Experiments on placental circulation and transplacental transfer in exteriorized foetuses in hypoxia and after asphyxia in guinea pigs.
Experiments were carried out on near term pregnant guinea pigs. Cesarean section was performed and by exteriorization of the foetuses the placental stage of labor was simulated. In one group of foetuses, chosen at random, we induced hypoxia, and in an another series of experiments asphyxia, each group with its own control. The results of acid-base values, experimental antipyrine transplacental transfer studies and the survival rate of foetuses, showed that it is advantageous for the newborn animal if we preserve the placental function in such conditions immediately post partum. Further study is necessary to determine to what degree and under what conditions our experimental observations are applicable to human perinatology.


Characterization and Application of Antilisterial Enterocins on Model Fresh Cheese.
Enterococcus faecalis strains isolated from an artisanal cheese were selected based on enterocin production against Listeria monocytogenes. The strains formed biofilms and presented high hydrophobic character and good autoaggregation and coaggregation capacity with L. monocytogenes. Strains L3A21M3 and L3B1K3 presented high survival under gastrointestinal conditions, were able to adhere to human intestinal cells (Caco-2 and HT-29), and blocked the adhesion and invasion of L. monocytogenes. The antilisterial activity of enterocins was not affected by pH (2 to 12), heating (100°C), and chemical and surfactant agents. However, strains L3A21M3 and L3A21M8 produced thermolabile enterocins, which were also sensible to extreme pH values. Enterocins exhibited a bacteriostatic mode of action against L. monocytogenes, and maximum production was observed during the stationary phase. Common enterocin structural genes were not detected by PCR amplification with specific primers, although an exhaustive screening was not performed. The enterocin produced by the L3B1K3 strain was purified and applied to model cheeses contaminated with L. monocytogenes. This enterocin reduced survival of L. monocytogenes on fresh cheeses in a dose-dependent manner. The highest dose tested (2,048 arbitrary units per g of cheese) was effective in reducing the pathogen counts to undetectable values throughout storage (6 to 72 h). These results suggest that these strains have great potential to be used as biopreservatives in the food industry and also as probiotics, with the potential to prevent L. monocytogenes gastrointestinal infection.


Bovine peripheral blood leukocyte population dynamics following treatment with recombinant bovine interferon-alpha I1.
The in vitro functional activity of bovine peripheral blood lymphocytes and the population dynamics of the major peripheral blood leukocyte subpopulations were investigated following the administration of recombinant bovine interferon-alpha I1 (rBoIFN-alpha I1). The intramuscular injection of rBoIFN-alpha I1 induced a 24-h lymphopenia characterized by a decrease in both circulating T and non-T/non-B lymphocytes. An increased CD4/CD8 ratio indicated that there was a relatively greater depletion of the CD8 equivalent subpopulation of T lymphocytes. These changes in lymphocyte trafficking were observed in the absence of a cortisolemia. Coincidental with the lymphopenia, there was a marked decrease in the amplitude of mitogen-induced lymphocyte proliferation responses that probably was caused by a numerical deficit rather than functional deficit in the responder T cells.


Impaired prosaposin secretion during nerve regeneration in diabetic rats and protection of nerve regeneration by a prosaposin-derived peptide.
Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) after sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia, and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats, and that prosaptide TX14(A) can improve aspects of nerve regeneration.


Superconducting gap for a two-leg t-J ladder.
Single-particle diagonal and off-diagonal Green's functions of a two-leg t-J ladder at 1/8 doping are investigated by exact diagonalizations techniques. A numerically tractable expression for the superconducting gap is proposed and the frequency dependence of the real and imaginary parts of the gap are determined. The role of the low-energy gapped spin modes, whose energies are computed by a (one-step) contractor renormalization procedure, is discussed.


Identification and characterization of Burkholderia multivorans CCA53.
A lignin-degrading bacterium, Burkholderia sp. CCA53, was previously isolated from leaf soil. The purpose of this study was to determine phenotypic and biochemical features of Burkholderia sp. CCA53. Multilocus sequence typing (MLST) analysis based on fragments of the atpD, gltD, gyrB, lepA, recA and trpB gene sequences was performed to identify Burkholderia sp. CCA53. The MLST analysis revealed that Burkholderia sp. CCA53 was tightly clustered with B. multivorans ATCC BAA-247T. The quinone and cellular fatty acid profiles, carbon source utilization, growth temperature and pH were consistent with the characteristics of B. multivorans species. Burkholderia sp. CCA53 was therefore identified as B. multivorans CCA53.


Nanosecond Melting and Recrystallization in Shock-Compressed Silicon.
In situ, time-resolved, x-ray diffraction and simultaneous continuum measurements were used to examine structural changes in Si shock compressed to 54 GPa. Shock melting was unambiguously established above ∼31-33 GPa, through the vanishing of all sharp crystalline diffraction peaks and the emergence of a single broad diffraction ring. Reshock from the melt boundary results in rapid (nanosecond) recrystallization to the hexagonal-close-packed Si phase and further supports melting. Our results also provide new constraints on the high-temperature, high-pressure Si phase diagram.


Trillion virion delay: time from testing positive for HIV to presentation for primary care.
Human immunodeficiency virus (HIV)-infected individuals' initial presentation to medical care frequently occurs at a point of advanced immunosuppression. To investigate the time between HIV testing and presentation to primary care. Also to examine factors associated with delayed presentation. One hundred eighty-nine consecutive outpatients without prior primary care for HIV infection were assessed at 2 urban hospitals: Boston City Hospital, Boston, Mass, and Rhode Island Hospital, Providence. Sociodemographics, alcohol and drug use, social support, sexual beliefs and practices, and HIV testing issues were examined in bivariate and multivariate analyses for association with delay in presentation to primary care after positive test results for HIV. Of 189 patients, 74 (39%) delayed seeking primary care for more than 1 year, 61 (32%) delayed for more than 2 years, and 35 (18%) for more than 5 years after an initial positive HIV serologic evaluation. The median CD4+ cell count of subjects was 0.28 x 10(9)/L (range, 0.001-1.71 x 10(9)/L). In multiple linear regression analysis the following characteristics were found to be associated with delayed presentation to primary care after HIV testing: history of injection drug use (P<.001); not having a living mother (P=.01); not having a spouse or partner (P=.08); not being aware of HIV risk before testing (P<.001); and being notified of HIV status by mail or telephone (P=.002). An interaction effect between sex and screening for alcohol abuse was significant (P=.03) and suggested longer delays for men with positive screening test results (CAGE [an alcoholism screening questionnaire containing 4 structured questions], 2+) compared with men without positive screening test results or women. Patients with positive HIV test results often delay for more than a year before establishing primary medical care. Information readily available at the time of HIV testing concerning substance abuse, social support, and awareness of personal HIV risk status is useful in identifying patients who are at high risk of not linking with primary care. Patients who were notified of their HIV status by mail or telephone delayed considerably longer than those notified in person. Efforts to ensure primary care linkage at the time of notification of positive HIV serostatus are necessary to maximize benefits for both individual and public health and should be an explicit task of posttest counseling.


Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator-associated pneumonia.
The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was appropriate for every patient. Patients with methicillin-resistant Staphylococcus aureus VAP were older, had higher disease-severity scores, and had been on mechanical ventilation longer at onset of VAP. Factors associated with 28-day mortality retained by multivariate logistic regression analysis were: age (odds ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1 organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p = 0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22). The percentages of infection relapse or superinfection did not differ significantly between the two patient groups. In conclusion, after controlling for clinical and physiologic heterogeneity between groups, methicillin resistance did not significantly affect 28-day mortality of patients with Staphylococcus aureus VAP receiving appropriate antibiotics.


Association between fasting blood glucose levels and stroke events: a large-scale community-based cohort study from China.
Diabetes mellitus has been associated with stroke. However, the association between fasting blood glucose (FBG) and stroke risk in a general population remains not clear. The purpose of our study was to examine the FBG levels on subsequent stroke risk in a community-based cohort in China. Prospective cohort study, employing Cox proportional hazard model to analyse the association of FBG levels with stroke risk. A community-based cohort study included adults participating in a baseline survey conducted in 2013 in Changshu, eastern China. 16 113 participants were recruited with a multistage sampling method, excluding participants with severe disability, severe cancer, severe psychiatric disturbance or previous stroke before enrolment. Stroke events. During a median follow-up of 5.5 years, 417 incident cases of stroke were identified. The adjusted HR for total and ischaemic stroke for participants in the fourth quartile of FBG compared with the first quartile was 1.44 (95% CI 1.07 to 1.94) and 1.57 (95% CI 1.11 to 2.21), respectively. FBG levels of ≥7.0 mmol/L were associated with an increased risk of stroke based on two clinical classifications (American Diabetes Association: 1.68 (1.24 to 2.27); WHO: 1.62 (1.21, 2.13)). In stratified analyses, risk associations existed in women (HR: 1.92, 95% CI 1.22 to 3.01) and postmenopausal women (HR: 1.68, 95% CI 1.06 to 2.68) for the fourth quartile versus the first. More importantly, the meta-analysis observed a positive association between FBG levels and stroke risk (pooled HR: 1.70, 95% CI 1.27 to 2.29; n=7)). Higher FBG level was independently associated with an increased risk of stroke in Chinese adults, especially significant in women.


Electroorganic synthesis of catecholthioethers.
[reaction: see text] It is demonstrated that o-quinones, generated by the electrochemically driven oxidation of the catechols (1a-d) at physiological pH, are rapidly scavenged by 2-mercaptobenzoxazole (3) to give related catecholthioethers (4a-d) via an EC electrochemical mechanism pathway. The electrochemical syntheses of 4a-d have been successfully performed in one-pot in ambient conditions and in an undivided cell using an environmentally friendly method with high atom economy.


"Smallball" evaluation: a prescription for studying community-based information interventions.
This paper argues that focused evaluation studies of community-based informational interventions conducted over the life-cycle of the project ("smallball" studies) are more informative and useful than randomized experiments conducted only at the project's conclusion ("powerball" studies). Based on two contrasting strategies in baseball, smallball and powerball studies are compared and contrasted, emphasizing how the distinctive features of community-based interventions lend advantage to smallball approaches. Smallball evaluations have several important advantages over powerball evaluations: before system development, they ensure that information resources address real community needs; during deployment, they ensure that the systems are suited to the capabilities of the users and to community constraints; and, after deployment, they enable as much as possible to be learned about the effects of the intervention in environments where randomized studies are usually impossible. Many in informatics see powerball studies as the only legitimate form of evaluation and so expect powerball studies to be done. These expectations should be revised in favor of smallball studies.


Improving Plant Nitrogen Use Efficiency through Alteration of Amino Acid Transport Processes.
Improving the efficiency of nitrogen (N) uptake and utilization in plants could potentially increase crop yields while reducing N fertilization and, subsequently, environmental pollution. Within most plants, N is transported primarily as amino acids. In this study, pea (Pisum sativum) plants overexpressing AMINO ACID PERMEASE1 (AAP1) were used to determine if and how genetic manipulation of amino acid transport from source to sink affects plant N use efficiency. The modified plants were grown under low, moderate, or high N fertilization regimes. The results showed that, independent of the N nutrition, the engineered plants allocate more N via the vasculature to the shoot and seeds and produce more biomass and higher seed yields than wild-type plants. Dependent on the amount of N supplied, the AAP1-overexpressing plants displayed improved N uptake or utilization efficiency, or a combination of the two. They also showed significantly increased N use efficiency in N-deficient as well as in N-rich soils and, impressively, required half the amount of N to produce as many fruits and seeds as control plants. Together, these data support that engineering N allocation from source to sink presents an effective strategy to produce crop plants with improved productivity as well as N use efficiency in a range of N environments.


Gut microbiota and sepsis: from pathogenesis to novel treatments.
This review summarizes recent progress in our understanding of the role of the gut microbiota in sepsis pathogenesis and outlines the potential role of microbiota-targeted therapies. The composition of the gut microbiome is profoundly distorted during sepsis, with a loss of commensal bacteria and an overgrowth of potential pathogenic micro-organisms. These alterations also extend to nonbacterial intestinal inhabitants. Disruptions of these intestinal communities are associated with both an increased susceptibility to develop sepsis, as well as a higher risk of adverse outcomes. Preclinical studies have characterized the effects of several microbiota-derived metabolites (such as D-lactate, butyrate, and deoxycholic acid) on enhancing the host immune response during critical illness. Microbiota-targeted therapies (e.g. probiotics or fecal microbiota transplantation) might be of benefit, but can also be associated with increased risks of bloodstream infections. Emerging evidence display an important role of gut micro-organisms (including bacteria, fungi, eukaryotic viruses, and bacteriophages) and their derived metabolites in both the susceptibility to, as well as outcomes of sepsis. Despite recent progress in the mechanistic understanding of microbiota-mediated protection, clinical breakthroughs in the development of microbiota-based prognostic tools or therapies are thus far lacking in the field of sepsis.


Nuclear receptors in the cross-talk of drug metabolism and inflammation.
Inflammation and infection have long been known to affect the activity and expression of enzymes involved in hepatic and extrahepatic drug clearance. Significant advances have been made to elucidate the molecular mechanisms underlying the complex cross-talk between inflammation and drug-metabolism alterations. The emergent role of ligand-activated transcriptional regulators, belonging to the nuclear receptor (NR) superfamily, is now well established. The NRs, pregnane X receptor, constitutive androstane receptor, retinoic X receptor, glucocorticoid receptor, and hepatocyte nuclear factor 4, and the basic helix-loop-helix/Per-ARNT-Sim family member, aryl hydrocarbon receptor, are the main regulators of the detoxification function. According to the panel of mediators secreted during inflammation, a cascade of numerous signaling pathways is activated, including nuclear factor kappa B, mitogen-activated protein kinase, and the Janus kinase/signal transducer and activator of transcription pathways. Complex cross-talk is established between these signaling pathways regulating either constitutive or induced gene expression. In most cases, a mutual antagonism between xenosensor and inflammation signaling occurs. This review focuses on the molecular and cellular mechanisms implicated in this cross-talk.


Does heart rate really predict survival in septic shock?
Normalisation of heart rate after 24 hours of treatment is proposed to predict the survival outcome in septic shock patients. The medical and surgical patients charts from 1991-1993 were selected for the diagnosis of septic shock (according to the definition of ACCP/SCCM Consensus Conference), and reviewed. Also included were patients with available variables to complete APACHE II and septic severity score. Tachycardia was observed more in the non-survivors (9 patients) both in shock (107.8 vs 93.4) and non-shock states (112.3 vs 93.2). Heart rate in the survival group decreased below the cut-off value, which is 95 beats/min, as specified by ACCP/SCCM. Comparison between APACHE II and SSS was not well correlated because of the small sample size. Elements in creating a predictor and its categorisation are mentioned. Heart rate was concluded to be a simple predictor reflecting physiologic derangements in septic shock. It is recommended that further study needs to be carried out to unravel a predictor of clinical value in terms of practicality, especially that involving the inflammatory aspect of the disease process.


Sex-dependent association between coronary vessel dominance and cardiac syndrome X: a case-control study.
Previous studies have demonstrated the relevance of left coronary artery dominance in the outcome and prognosis of obstructive coronary artery disease (CAD). However, no studies have investigated the influence of coronary vessel dominance on non obstructive CAD. The aim of this study was to establish the association of left and mixed dominance of the major epicardial arteries with the development of non obstructive CAD and evaluate potential sex-dependent differences in the coronary artery supply. A total of 484 patients underwent the same diagnostic procedures. The patients were divided into two groups based on their coronary angiogram results: the control group (242 patients with obstructive CAD; coronary artery stenosis of ≥50%) and the experimental group (242 patients with non obstructive CAD; coronary artery stenosis of <50%). Significantly more women than men were affected by non obstructive CAD (P = 0.005). Left dominance was more frequent in the non obstructive CAD group than in the control group (P = 0.018) and was more pronounced in women than in men (P = 0.013). Among men with non obstructive CAD, a left supply was more frequent than a mixed supply (P = 0.012). Women with non obstructive CAD had a higher frequency of a left supply, whereas a mixed supply was less frequent in men than in patients with obstructive CAD (P = 0.013 and 0.018, respectively). These results suggest that left dominance (particularly in women) and the absence of a mixed supply in men could cause regional ischemia, thus affecting the development of non obstructive CAD. Furthermore, sex may determine the incidence of specific coronary artery supply types, therefore influencing disease development and prognosis.


The effect of L-arginine on arterial stiffness and oxidative stress in chronic kidney disease.
Chronic kidney disease (CKD) is a growing problem worldwide. The disproportionate increase in the burden of cardiovascular disease in patients with CKD may be significantly contributed by nontraditional risk factors. Increased arterial stiffness has been recognized as an important player in contributing to this morbidity and mortality. The aim of this study was to report the effect of L-arginine on arterial stiffness and oxidative stress in patients with CKD. Thirty patients with stage II to IV CKD were administered 9 g of L- arginine per day orally for a period of 12 weeks. The parameters evaluated at baseline, at 8 weeks, and at the end of 12 weeks were serum nitric oxide (NO), carotid.femoral pulse wave velocity (cf PWV), and radial artery pulse wave analysis which included aortic augmentation pressure (AP), aortic augmentation index (AIx), aortic augmentation index at heart rate of 75 bpm, subendocardial viability ratio, radial pressures, and central aortic pressure. Serum levels of NO and malondialdehyde (MDA) were estimated at baseline and at the end of 12 weeks. The control group was composed of age- and sex-matched healthy individuals. Twenty-five patients completed the study. Two patients were lost to follow.up; three patients developed adverse events and were excluded. Baseline NO levels were low (13.55 ± 7.49 μM/L) in all the subjects. Administration of L-arginine resulted in improvement in the carotid-radial PWV (m/s) (10.08 ± 1.72 at baseline to 8.56 ± 1.16 by 12 weeks; P < 0.001), cf PWV (m/s) (13.06 ± 2.65 at baseline to 10.62 ± 1.93 at 12 weeks; P < 0.001), Aortic Augmentation Index (%) (32 ± 10.34 at baseline to 17.84 ± 8.05 at 12 weeks; P < 0.001), aortic augmentation pressure (mm of Hg) (14.03 ± 6.53 at baseline to 7.12 ± 3.85 at 12 weeks; P < 0.001), and NO (μM/L) (13.55 ± 7.49 at baseline to 30.22 ± 9.8 at 12 weeks; P < 0.001). There was no significant change in the levels of MDA (nanomol/ml) (20.0 ± 10.14 at baseline and 19.16 ± 9.36 at 12 weeks; P = ns). In conclusion, PWV, an indicator of arterial stiffness, is greatly increased even in the early stages of CKD. Supplementation of L-arginine is a safe, well-tolerated, and effective way of improving endothelial dysfunction in patients with CKD.


Screening of Multitarget-Directed Natural Compounds as Drug Candidates for Alzheimer's Disease Using In Silico Techniques: Their Extraction and In Vitro Validation.
Alzheimer's disease (AD) is a neurodegenerative disorder that impairs neurocognitive function. Acetylcholinesterase (AChE) and β-site APP cleaving enzyme 1 (BACE1) are the two main proteins implicated in AD. Indeed, the major available commercial drugs (donepezil, rivastigmine, and galantamine) against Alzheimer's are AChE inhibitors. However, none of these drugs are known to reverse or reduce the pathophysiological condition of the disease since there are multiple contributing factors to AD. Therefore, there is a need to develop a multitarget-directed ligand approach for its treatment. In the present study, plant bioactive compounds were screened for their AChE and BACE1 inhibition potential by conducting molecular docking studies. Considering their docking score and pharmacokinetic properties, limonin, peimisine, serratanine B, and withanolide A were selected as the lead compounds. Molecular dynamics simulations of these protein-ligand complexes confirmed the conformational and energetically stabilized enzyme-inhibitor complexes. The inhibition potential of the lead compounds was validated by in vitro enzyme assay. Withanolide A inhibited AChE (IC50 value of 107 μM) and showed mixed-type inhibition. At this concentration, it inhibited BACE1 activity by 57.10% and was stated as most effective. Both the compounds, as well as their crude extracts, were found to have no cytotoxic effect on the SH-SY5Y cell line.