The impact of high progesterone levels in the follicular phase of in vitro fertilization (IVF) cycles: a comparative study.
Estrogen (E2) and plasma progesterone (P4) levels are valuable parameters for follicular development in in vitro fertilization (IVF) cycles. Furthermore, the progesterone concentration prior to, during, and following human chorionic gonadotropin (hCG) administration is an important marker for the detection of early luteinization and premature ovulation. The pattern of hormonal profile in relation to the number of oocytes retrieved, fertilized, and cleaved and the fate of the pregnancies achieved were compared in three groups of patients treated by the same protocol. Group I included 22 women who conceived with high progesterone levels on day hCG + 1 (P4, greater than 2.5 ng/ml). Group II included 43 women who conceived with low P4 values (P4, less than 2.5 ng/ml), while group III included 46 patients in whom no pregnancies occurred. A significant decrease in fertilization, cleavage, and pregnancy rates was observed in patients with high progesterone levels on day hCG + 1, compared to those with normal levels. Nevertheless, it is suggested that cycles with high P4 levels in the preovulatory phase should not be canceled, as a fair chance for pregnancy still exists.


Barriers to conducting clinical research in reproductive medicine: Greece.
In Greece, procedures for obtaining funding and/or state approval for a research project are lengthy, hinder collaboration between centers, and may render projects outdated.


Pilot Randomized Controlled Trial of an Intervention to Improve Coping with Intersectional Stigma and Medication Adherence Among HIV-Positive Latinx Sexual Minority Men.
We developed and pilot-tested an eight-session community-based cognitive behavior therapy group intervention to improve coping with intersectional stigma, address medical mistrust, and improve antiretroviral treatment adherence. Seventy-six HIV-positive Latinx sexual minority men (SMM; 38 intervention, 38 wait-list control) completed surveys at baseline, and 4- and 7-months post-baseline. Adherence was electronically monitored. Intention-to-treat, repeated-measures regressions showed improved adherence in the intervention vs. control group from baseline to follow-up [electronically monitored: b (95% CI) 9.24 (- 0.55, 19.03), p = 0.06; self-reported: b (95% CI) 4.50 (0.70, 8.30), p = .02]. Intervention participants showed marginally decreased negative religious coping beliefs in response to stigma [b (95% CI) = - 0.18 (- 0.37, 0.01), p = .06], and significantly lower medical mistrust [b (95% CI) = - 0.47 (- 0.84, - 0.09), p = .02]. Our intervention holds promise for improving HIV outcomes by empowering Latinx SMM to leverage innate resilience resources when faced with stigma.ClinicalTrials.gov ID (TRN): NCT03432819, 01/31/2018.


DNA damage emergency: cellular garbage disposal to the rescue?
The proteasome is a cellular machine found in the cytosol, nucleus and on chromatin that performs much of the proteolysis in eukaryotic cells. Recent reports show it is enriched at sites of double-stranded DNA breaks (DSBs) in mammalian cells. What is it doing there? This review will address three possibilities suggested by recent reports: in degrading proteins after their ubiquitination at and eviction from chromatin; as a deubiquitinase, specific to the antagonism of ubiquitin conjugates generated as part of the signalling of a DSB; and as a functional component of DNA repair mechanism itself. These findings add complexity to the proteasome as a potential therapeutic target in cancer treatment.


Ten-year protocol biopsy findings of renal allografts in the calcineurin inhibitor era.
Ten-year protocol biopsies were performed in 16 patients treated with calcineurin inhibitor (CNI) continuously. All kidney grafts were functioning well at the time of biopsy with the mean serum creatinine level of 1.6 +/- 0.8 mg/dL. The specimen of biopsy showed various degrees of tissue injury. According to the Banff grading, allograft glomerulopathy (cg) was observed in one case. Interstitial fibrosis (ci) and tubular atrophy (ct) were observed more frequently in 13 (81%) and 15 (93%) cases, respectively. Fibrous intimal thickening (cv) was seen in one (7%) case. Arteriolar hyaline thickening (ah) was seen in 14 (87%) cases. These findings were associated with chronic rejection in one case, recurrence of original disease in four (25%) cases, toxicity of CNI in 14 (87%) cases. Longer follow-up studies are needed to confirm whether CNI should be continued or not in the long-term period following kidney transplantation for better graft survival.


[Drug resistance testing of Mycobacterium tuberculosis isolates from sputum in Chad].
Culture and resistance testing of Mycobacterium tuberculosis are not regularly performed in Chad. Sputa were obtained from three different categories of hospitals (district, regional and national) in Chad. All examined sputa were smear-positive and were investigated by culture and drug resistance testing for first-line antituberculosis drugs. From 232 sputa positive for acid-fast bacilli, 135 isolates of M. tuberculosis from different patients (46 women, 89 men, mean age 34 years) were analyzed. All the patients except one corresponded to new cases of tuberculosis. In total, 27 out of 135 isolates (20%) were resistant to at least one major antituberculosis drug. Resistance to isoniazid was the most frequent resistance observed, with 18 isolates (13%) presenting at least this resistance. Three isolates (2.2%) were resistant to isoniazid and rifampicin (multidrug resistance MDR) including one isolate being concomitantly resistant to streptomycin and ethambutol. The resistance rate differed in relation to the category of the hospital; the most important resistance rate was observed in regional hospitals (33%), while it was 16% and 14% in the national and district hospitals, respectively. HIV serology was performed in 81 patients, among whom 20 (25%) were positive. This is the first study that shows that drug resistance of M. tuberculosis is present in Chad. Besides single drug-resistant isolates, multidrug-resistant strains of M. tuberculosis could also be identified. This result highlights the urgency of initiating actions to detect drug resistance and limit the spread of drug-resistant strains.


The Fokker-Planck equation of the superstatistical fractional Brownian motion with application to passive tracers inside cytoplasm.
By collecting from literature data experimental evidence of anomalous diffusion of passive tracers inside cytoplasm, and in particular of subdiffusion of mRNA molecules inside live Escherichia coli cells, we obtain the probability density function of molecules' displacement and we derive the corresponding Fokker-Planck equation. Molecules' distribution emerges to be related to the Krätzel function and its Fokker-Planck equation to be a fractional diffusion equation in the Erdélyi-Kober sense. The irreducibility of the derived Fokker-Planck equation to those of other literature models is also discussed.


Impact of estrogen receptor agonists and model of menopause on enzymes involved in brain metabolism, acetyl-CoA production and cholinergic function.
Our goal is to understand how loss of circulating estrogens and estrogen replacement affect brain physiology and function, particularly in brain regions involved in cognitive processes. We recently conducted a large metabolomics study characterizing the effects of rodent models of menopause and treatment with estrogen receptor (ER) agonists on neurochemical targets in hippocampus, frontal cortex, and striatum. Here we characterize effects on levels of several key enzymes involved in glucose utilization and energy production, specifically phosphofructokinase, glyceraldehyde 3-phosphate dehydrogenase, and pyruvate dehydrogenase. We also evaluated effects on levels of β-actin and α-tubulin, choline acetyltransferase (ChAT) activity, and levels of ATP citrate lyase. All experiments were conducted in young adult rats. Experiment 1 compared the effects of ovariectomy (OVX), a model of surgical menopause, and 4-vinylcyclohexene diepoxide (VCD)-treatments, a model of transitional menopause, with tissues collected at proestrus and at diestrus. Experiment 2 used a separate cohort of rats to evaluate the same targets in OVX and VCD-treated rats treated with estradiol or with selective ER agonists. Differences in the expression of metabolic enzymes between cycling animals and models of surgical and transitional menopause were detected. These differences were model-, region- and time- dependent, and were modulated by selective ER agonists. Collectively, the findings demonstrate that loss of ovarian function and ER agonist treatments have differing effects in OVX vs. VCD-treated rats. Differences may help to explain differences in the effects of estrogen treatments on brain function and cognition in women who have experienced surgical vs. transitional menopause.


Knowledge and perception towards net care and repair practice in Ethiopia.
Long-lasting insecticidal nets (LLINs) are a key malaria control intervention. Although LLINs are presumed to be effective for 3 years under field or programmatic conditions, net care and repair approaches by users influence the physical and chemical durability. Understanding how knowledge, perception and practices influence net care and repair practices could guide the development of targeted behavioural change communication interventions related to net care and repair in Ethiopia and elsewhere. This population-based, household survey was conducted in four regions of Ethiopia [Amhara, Oromia, Tigray, Southern Nations Nationalities Peoples Region (SNNPR)] in June 2015. A total of 1839 households were selected using multi-stage sampling procedures. The household respondents were the heads of households. A questionnaire was administered and the data were captured electronically. STATA software version 12 was used to analyse the data. Survey commands were used to account for the multi-stage sampling approach. Household descriptive statistics related to characteristics and levels of knowledge and perception on net care and repair are presented. Ordinal logistic regression was used to identify factors associated with net care and repair perceptions. Less than a quarter of the respondents (22.3%: 95% CI 20.4-24.3%) reported adequate knowledge of net care and repair; 24.6% (95% CI 22.7-26.5%) of the respondents reported receiving information on net care and repair in the previous 6 months. Thirty-five per cent of the respondents (35.1%: 95% CI 32.9-37.4%) reported positive perceptions towards net care and repair. Respondents with adequate knowledge on net care and repair (AOR 1.58: 95% CI 1.2-2.02), and those who discussed net care and repair with their family (AOR 1.47: 95% CI 1.14-1.89) had higher odds of having positive perceptions towards net care and repair. The low level of reported knowledge on net care and repair, as well as the low level of reported positive perception towards net repair need to be addressed. Targeted behavioural change communication campaigns could be used to target specific groups; increased net care and repair would lead to longer lasting nets.


Hematology of the common Indian frog Rana tigrina. III. Hemoglobin and hematocrit.
The hemoglobin and hematocrit values studied in two years averaged 6.22 and 3.87 g/100 ml and 31.8 and 19.5 percent in female and male Rana tigrina respectively. The peak values in females and males are observed in May and June respectively. The breeding season is characterized by low hemoglobin and hematocrit values. The starvation upto 28 days is observed to cause a decrease in hemoglobin level.


Penbactam for Helicobacter pylori eradication: a randomised comparison of quadruple and triple treatment schedules in an Iranian population.
Selection of the best drug regimens for eradication of Helicobacter pylori infection especially in patients at risk of peptic ulcer relapses and the development of complications is challenging. This study assessed and compared the efficacy of the two common PPI based triple therapies to a quadruple therapy including PPI, metronidazole, amoxicillin and a bismuth compound in Iranian population. Three hundred and thirty patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomly assigned to one of the three treatment protocols all given twice daily: (a) A 14-day quadruple therapy (OMAB group) comprising omeprazole 20mg, metronicazole 500 mg, amoxicillin 1g, and bismuth subcitrate 240 mg; (b) A 14-day triple regimen (OCP group) comprising omeprazole 20mg plus clarithromycine 500 mg and penbactam 750 mg and (c) A 14-day triple regimen (OCA group) comprising omeprazole 20mg plus clarithromycine 500 mg and amoxicillin 1g. Cure was defined as a negative urea breath test at least six weeks after treatment. The per-protocol eradication rates achieved with both OCP regimen (87.0%) and OCA treatment (90.8%) were significantly higher than the OMAB treatment protocol (56.0%); however, no significant difference emerged in eradication rates between the two triple treatment schedules. No significant differences between the groups were found in most side-effects. Two-week quadruple therapy showed a lower eradication rate compared to common triple treatment schedules when used as first-line eradication treatment for H. pylori infection in Iranian population.


Polycyclic aromatic hydrocarbons in farmland soils around main reservoirs of Jilin Province, China: occurrence, sources and potential human health risk.
Study on the occurrence, sources and potential human health risk of polycyclic aromatic hydrocarbons in farmland soils around reservoirs is of great significance for the people drinking water security. In the present study, representative farmland soil samples around main reservoirs of Jilin Province, China, were investigated for 16 PAHs. The total concentrations of 16 priority PAHs in 32 farmland soil samples ranged from 602.12 to 1271.87 ng/g, with an arithmetic average of 877.23 ng/g, and the sum of seven carcinogenic PAH concentrations ranged from 30.07 to 710.02 ng/g, with a mean value of 229.04 ng/g. The 3-ring and 4-ring PAHs were major exist and account for 45.78 and 32.03%, respectively. Non-cancer and cancer risk of pollutants were calculated, and the results indicate that the complex PAHs in farmland soils were not considered to pose significant health effects. The isomer ratios Fla/(Fla + Pyr) and BaA/(BaA + Chr) show that the PAHs in soils were generally derived from biomass and coal combustion.


[Conservative therapy of female stress incontinence. Double-blind study with the alpha-sympathomimetic midodrin].
Midodrine, an alpha-adrenergic agent, was tested in a double-blind randomized fashion in 50 female patients suffering from stress incontinence. 61,5% of the patients receiving midodrine became completely continent, 23,1% improved and 15,4% were considered failure. The results obtained, have been statistically significant.


Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases.
Substrates enter the cylindrical 20S proteasome through a gated channel that is regulated by the ATPases in the 19S regulatory particle in eukaryotes or the homologous PAN ATPase complex in archaea. These ATPases contain a conserved C-terminal hydrophobic-tyrosine-X (HbYX) motif that triggers gate opening upon ATP binding. Using cryo-electron microscopy, we identified the sites in the archaeal 20S where PAN's C-terminal residues bind and determined the structures of the gate in its closed and open forms. Peptides containing the HbYX motif bind to 20S in the pockets between neighboring alpha subunits where they interact with conserved residues required for gate opening. This interaction induces a rotation in the alpha subunits and displacement of a reverse-turn loop that stabilizes the open-gate conformation. This mechanism differs from that of PA26/28, which lacks the HbYX motif and does not cause alpha subunit rotation. These findings demonstrated how the ATPases' C termini function to facilitate substrate entry.


Surgical management of spastic thumb-in-palm deformity in adults with brain injury.
Spastic thumb-in-palm deformity was surgically treated in 27 adults with brain injury. Procedures included muscle lengthening, recession, or release, arthrodesis of the thumb interphalangeal joint, or Z-plasty of the thumb web space. At mean follow-up of 39 months, 23 of 27 had a satisfactory correction. Unsatisfactory results included two with inadequate correction and two with over-correction. Surgical treatment of this entity requires careful preoperative planning, addressing predominantly those spastic muscles responsible for the deformity.


Organization of biologic therapy during the COVID-19 pandemic based on example of Dermatology Clinic Centre of Postgraduate Medical Education in Warsaw.
The COVID-19 pandemic spread to almost all countries in the world within a few months, necessitating changes in medical care for patients with SARS-CoV-2 infections as well as patients with various chronic diseases. Ensuring the safety of medical staff and patients in hospitals specializing in infectious diseases is a major logistical challenge. Psoriasis patients treated with immunosuppressive medications, including those under biologic therapy, are a special group. Many scientific societies do not recommend discontinuing therapy in patients without symptoms or confirmation of SARS-CoV-2 infection despite the potentially higher risk of respiratory tract infections in this patient population. Based on our own experience, we present the organization of the biologic therapy within the unit of a Single Specialty Infectious Hospital.


Effect of dexamethasone on protein extravasation in the brain in acute hypertension induced by amphetamine.
Amphetamine productes protein leakage in the brain when given to rats under nitrous oxide anesthesia. The blood-brain barrier dysfunction is caused by the combined effect of blood pressure increase and vasodilatation. In the present experiments pretreatment with dexamethasone, 2 mg.kg-1, diminished the amphetamine-induced extravasation of Evans blue albumin and 125IHSA in the rats' brain. Possible explanations to the effect of dexamethasone on cerebrovascular permeability are discussed.


Study of the non-clinical healing activities of the extract and gel of Portulaca pilosa L. in skin wounds in wistar rats: A preliminary study.
Portulaca pilosa L., belonging to the family Portulacaceae, is a common herbaceous plant in the Americas and in the Amazon, is popularly known as love-grown and is traditionally used as an aid in the treatment of burns, buds, insect bites and wound healing. This study aims to evaluate the non-clinical topical healing activity of the P. pilosa gel (GPP) and the propyleneglycol extract of P. pilosa (EPP) in Wistar rats. For the healing activity, wistar rats were divided into the following groups: negative control (GVE - vehicle, 150mg/kg), positive control (Fibrinase®- FIB, 100U/kg), Portulaca pilosa gel 10%, (GPP, 150mg/kg), and propylenglycollic extract of Portulaca pilosa (EPP, 150 mg/kg), which were submitted to a surgical procedure to obtain the wounds, and were treated topically for 7days. After treatment, the treated area was removed and a histopathological analysis was performed. The EPP when analyzed in HPLC was able to identify the presence of gallic acid. EPP significantly modulated the tissue inflammatory response, presenting low number of inflammatory cells in the histopathological study. Treatment with EPP and GPP significantly stimulated angiogenesis and this response was superior to the fibrinase® group. Treatment with EPP and GPP significantly stimulated the proliferation of fibroblasts. The groups treated with EPP and GPP presented an organization pattern of the epidermis and dermis better than the control group, with a mild inflammatory process, with fibroblast proliferation and increased formation of collagen fibers. Thus, from the results obtained it can be suggested that the phytochemical marker of the P. pilosa species for healing activity is gallic acid and, together with the macroscopic and microscopic findings triggered by the topical applications of EPP and GPP, it can be concluded that this plant species has topical healing activity, with great potential for use, since this pharmacological action is associated with a possible topical anti-inflammatory activity.


Life expectancy of brain impaired, chronically ventilated children.
We present a 5-year survival profile of 42 children and adolescents between 1 to 21 years of age in an immobile minimally conscious state, chronically dependent on supportive ventilation. Data were collected from a 22-bed pediatric unit dedicated to this unique population, within a 350-bed geriatric hospital, between May 2006 and May 2011. The practice of ventilating children even in minimally conscious state stems from the unique cultural, religious, and ethnic background of the population in Israel. The 5-year survival probability was 48% (52% probability of death within 5 years, 26.5% within 2 years). No significant difference was found in the survival profile of patients admitted following hypoxic accidents (20 children) and those admitted with other problems such as genetic/metabolic diseases or brain anomalies (22). The mortality rate of male patients was higher than that of female patients, but the difference was not statistically significant. No difference in 5-year mortality rates was found between children of different ethnic backgrounds.


Differences in the content and turnover of noradrenaline in rat heart atria and ventricles and circadian-phase-dependency.
In light-dark-synchronized male rats the levels of noradrenaline in heart atria were about 3 times that found in heart ventricles. Noradrenaline turnover rate which were about 8-9 fold greater for the atria than for the ventricles displayed a circadian-phase-dependency with increased rates in the dark period in both parts of the rat heart.


The small world's problem is everyone's problem, not a reason to favor CNT over probabilistic decision theory.
The case for the superiority of Conviction Narrative Theory (CNT) over probabilistic approaches rests on selective employment of a double standard. The authors judge probabilistic approaches inadequate for failing to apply to "grand-world" decision problems, while they praise CNT for its treatment of "small-world" decision problems. When both approaches are held to the same standard, the comparative question is murkier.


Static magnetic fields increase the power intensity of EEG of man.
In static magnetic fields the power values of EEG are increased. This influence is different in the two cortical hemispheres and not the same for all EEG-frequencies. The increased control values following on inverted magnetic flux vector point to a - reversible - alteration of brain function induced by a static magnetic field.


Oxidative degradation of the organometallic iron(II) complex [Fe{bis[3-(pyridin-2-yl)-1H-imidazol-1-yl]methane}(MeCN)(PMe3)](PF6)2: structure of the ligand decomposition product trapped via coordination to iron(II).
Iron is of interest as a catalyst because of its established use in the Haber-Bosch process and because of its high abundance and low toxicity. Nitrogen-heterocyclic carbenes (NHC) are important ligands in homogeneous catalysis and iron-NHC complexes have attracted increasing attention in recent years but still face problems in terms of stability under oxidative conditions. The structure of the iron(II) complex [1,1'-bis(pyridin-2-yl)-2,2-bi(1H-imidazole)-κN(3)][3,3'-bis(pyridin-2-yl-κN)-1,1'-methanediylbi(1H-imidazol-2-yl-κC(2))](trimethylphosphane-κP)iron(II) bis(hexafluoridophosphate), [Fe(C17H14N6)(C16H12N6)(C3H9P)](PF6)2, features coordination by an organic decomposition product of a tetradentate NHC ligand in an axial position. The decomposition product, a C-C-coupled biimidazole, is trapped by coordination to still-intact iron(II) complexes. Insights into the structural features of the organic decomposition products might help to improve the stability of oxidation catalysts under harsh conditions.


Elevated plasma ammonia level in hepatic cirrhosis: role of glucagon.
Elevated plasma ammonia level in hepatic cirrhosis has been attributed to a lack of conversion of enteric ammonia into urea or to its entry into systemic circulation via portasystemic shunting, or to both. It is exaggerated by excessive protein intake. Because hyperglucagonemia is well documented in cirrhosis and a protein meal is an effective glucagon secretagogue, plasma glucose, insulin, glucagon, and ammonia levels were determined in 50 cirrhotic patients after an overnight fast. Effects of a protein meal were also assessed in 20 of these patients. Plasma glucose was normal and remained unaltered after a protein meal. Insulin, glucagon, and ammonia levels were elevated, but only in patients with advanced liver dysfunction. Ammonia levels correlated significantly with glucagon (r = 0.61, p less than 0.001), but not with insulin or glucose levels. Insulin and glucagon levels rose after a protein meal in all patients and controls; whereas a significant rise in the ammonia level occurred only in decompensated cirrhotics. Elevation of the ammonia level was significantly correlated with fasting glucagon (r = 0.54, p less than 0.05), as well as with glucagon response (r = 0.65, p less than 0.01), but not with basal insulin or insulin response. Furthermore, the rise in ammonia level occurred too early to be accounted for by enteric generation. Finally, direct effects of glucagon administration on plasma glucose and serum ammonia were examined in 15 cirrhotic patients. Glucose response was significantly blunted in cirrhotic patients as compared with normal subjects, whereas serum ammonia rose promptly but only in cirrhotics, with maximum rise being noted in cirrhotic patients with advanced liver dysfunction. This study, therefore, suggests that hyperglucagonemia may contribute significantly to hyperammonemia in hepatic cirrhosis.


A chromium terephthalate-based solid with unusually large pore volumes and surface area.
We combined targeted chemistry and computational design to create a crystal structure for porous chromium terephthalate, MIL-101, with very large pore sizes and surface area. Its zeotype cubic structure has a giant cell volume (approximately 702,000 cubic angstroms), a hierarchy of extra-large pore sizes (approximately 30 to 34 angstroms), and a Langmuir surface area for N2 of approximately 5900 +/- 300 square meters per gram. Beside the usual properties of porous compounds, this solid has potential as a nanomold for monodisperse nanomaterials, as illustrated here by the incorporation of Keggin polyanions within the cages.


HCV J6/JFH1 tilts the capability of myeloid-derived dendritic cells to favor the induction of immunosuppression and Th17-related inflammatory cytokines.
How HCV virus affects the function of dendritic cells (DCs) and their ability to induce CD4+ T cell response remains not fully understood. This study was done to elucidate the impact of HCV on the function of DCs and on DC's capability to induce CD4+ T-cell response. Monocyte-derived DCs (MoDCs) were treated with cell-culture HCV (HCVcc). The effects of HCVcc on DC maturation, CD40L-induced DC maturation, and cytokine production and the capacity of DCs to induce Th cytokine production of allogeneic CD4+ T cells were evaluated. HCVcc exposure increased expression of both IL-6 and IL-10 by MoDCs. HCV-exposed MoDCs also selectively facilitated allogeneic CD4+ T cells to further produce Th17-related cytokines interleukin 1 (IL-1), IL-6, and IL-17A. Pretreatment of IL-17A inhibited HCV production in Huh7.5 cells, suggesting that induction of Th17 cells may be beneficial to host anti-HCV immunity. Paradoxically, induction of IL-10 expression and the failure of HCV-exposed MoDCs to facilitate other Th cell development may hinder the anti-viral immunity. This study highlights both the therapeutic potential of IL-17A in treating HCV infection and the cautious consideration of HCV-induced immunosuppression in DC-based therapy.


Progression of keratoconus assessed by fourier analysis of videokeratography data.
To quantitatively document changes in corneal refractive parameters in relation to the progression of keratoconus over years. Retrospective observational case series. Eighty-five eyes of 64 patients with keratoconus who had undergone videokeratography examinations at least twice with an interval of 1 year or longer between each examination. By means of Fourier series harmonic analysis, topography data were decomposed into spherical component, regular astigmatism, decentration component, and higher order irregularity. Change rate of each parameter per year was calculated by use of the least squares method. All four refractive parameters were significantly larger in the keratoconic eyes than in the age-matched normal controls (P < 0.001, Student's t test). The yearly rate of change was significantly positive for spherical component (P = 0.008) and higher order irregular astigmatism (P = 0.015) but not for the regular astigmatism and decentration component. In eyes that showed apparent progression on color-coded maps, spherical component showed a significantly positive change rate per year (P = 0.002), but other parameters did not. In eyes without apparent progression, the yearly change rate of higher order irregular astigmatism was significantly larger than zero (P = 0.049). Keratoconus progression over years was quantitatively described. It was indicated that spherical equivalent is a manifest indicator for the apparent progression of keratoconus, and irregular astigmatism increases along with the natural course of the disease.


Correction: Cell lysis via acoustically oscillating sharp edges.
Correction for 'Cell lysis via acoustically oscillating sharp edges' by Zeyu Wang et al., Lab Chip, 2019, 19, 4021-4032, DOI: .


Multimodal Chiropractic Management of a Postsurgical Sternoclavicular Injury Utilizing Gamified Rehabilitation: A Case Report.
The purpose of this study was to describe how gamification was incorporated into postoperative rehabilitation of a patient recovering from a sternoclavicular dislocation. A 23-year-old man sought chiropractic care from an academic chiropractic clinic for persistent right-sided, sternoclavicular joint, moderate-to-severe pain that was exacerbated with shoulder movements and overhead activities. His shoulder was treated previously with reconstructive surgery and a 6-week trial of physical therapy; however, he reported minimal improvement in his pain, and his functional ability was suboptimal. Multimodal chiropractic treatment consisted of manual therapy in conjunction with active rehabilitation. The rehabilitation program incorporated gamification principles, such as competition, point scoring, and task focus. After 8 treatments, a clinically significant reduction in his upper extremity functional index score and numerical pain rating was observed. The patient was managed using a gamified approach to postsurgical sternoclavicular joint rehabilitation and responded positively. Chiropractors may consider including gamified, multimodal care for patients with postoperative musculoskeletal concerns.


A comparative study of prevalence-based incidence estimation techniques with application to dementia data in Germany.
Dementia is becoming a major health burden, which is mainly due to the increasing life expectancy in many developed countries. To describe the disease progression of individuals, multistate models are generally appropriate tools. These models allow the individuals to move along a path consisting of a finite number of disease states. We consider a simplifying illness-death model in which the subjects progress through the states healthy, diseased and dead. We use this model to study analytic relationships between the prevalence, incidence and mortality rates of irreversible diseases that have been applied in the past. One of these approaches is a rather recently proposed technique based on an ordinary differential equation (ODE). We conduct a simulation study to compare the performance of two suggested numerical approximations of this ODE with three alternative techniques, the common goal of which is to estimate age-specific incidence from cross-sectional information. The quality of the estimation methods is further explored using data on dementia in Germany. In the simulation scenarios as well as in the dementia data setting, the ODE method turns out to be the predominant technique with regard to the quality of the estimation of the known incidence regimes.


Differences in maternal responsive and directive behavior during free play with and without aided AAC.
Maternal directive and responsive behaviors were compared for 25 mothers and children with complex communication needs using two types of toys (familiar and unfamiliar toys). Each type of toy play was conducted with and without a single message speech-generating communication device (SGD) programmed to say "more." Rate percentages of coded intervals for maternal directive and responsive behaviors were analyzed using repeated measures ANOVAs. Results indicated that mothers used significantly more responsive behaviors when playing with their own familiar toys than with unfamiliar toys, but no differences in directiveness between types of play. Mothers showed no differences in responsivity or directiveness when the SGD was added to play interactions, indicating that the SGD did not introduce task features that detracted from the mothers' existing levels of responsivity with their children. Clinical implications are discussed.


Molecular characteristics of IgA in infant saliva.
Saliva was collected from 57 infants aged 6 weeks to 2.5 years and the molecular form of IgA was studied by centrifugation on sucrose density gradients. Two distinct populations were identified. Seventy-two per cent of the children had secretory IgA in their salivary secretions, while 28% had a molecular form corresponding to monomeric IgA. No samples with concurrent monomeric and secretory forms were detected. Monomeric IgA was not detected in any infant over 12 months of age. Secretory component was detected in all samples but was not associated with monomeric IgA. Forty-seven per cent of the samples contained IgA fragments of approximately 40,600 molecular weight. The presence of fragments dominated in the group of children with monomeric IgA. The presence of monomeric IgA in infant saliva did not result from degradation due to storage or proteolysis. The study demonstrated an apparent maturation sequence in the molecular form of IgA present in the salivary secretions of infants.


Gender differences in factors influencing electrocardiographic findings of left ventricular hypertrophy in severe aortic stenosis.
We investigated gender differences in factors influencing the electrocardiographic (ECG) findings of left ventricular hypertrophy (LVH) in patients with severe aortic stenosis (AS). The functional and geometric responses of the left ventricle to chronic pressure overload, such as hypertension and AS, have been reported to be different between men and women. However, gender differences in the factors influencing the ECG findings of LVH in pressure overload remain unknown. We conducted a retrospective observational study in consecutive patients with severe AS (aortic valve area (AVA) assessed by cardiac catheterization <1.0 cm(2)) without concomitant significant aortic regurgitation, mitral stenosis and/or regurgitation, conduction disturbance, or myocardial infarction (n = 35 males, 68 females). The ECG criteria were classified into three categories: (1) high voltage by the Sokolow-Lyon index associated with ST-T wave changes (with no digitalis therapy); (2) high voltage alone; and (3) normal. Groups 1 and 2 were defined as LVH on ECG. We compared the ECG findings in relation to the AS severity between genders. Women were older, but there were no significant differences in the prevalence of hypertension, AVA index (AVAI), mean pressure gradient or peak velocity across the AV, LV mass index (LVMI) derived from echocardiography or the distribution of ECG categories between genders. A multiple logistic regression analysis including age, gender, hypertension, AVAI, mean pressure gradient, and LVMI revealed that the LVMI (P = 0.001) and AVAI (P = 0.0434) were significantly related to the distribution of ECG categories. LVMI significantly predicted LVH on ECG in both genders, but AVAI was a predictive factor in only women. ECG LVH in patients with severe AS may be mainly reflected by LVMI in men and by both LVMI and AVAI in women. Factors other than AVA, such as end-stage disease and/or complicating factors such as hypertension, may underlie the observed differences in ECG findings of LVH between men and women.


UGT1A1 polymorphisms associated with risk of induced liver disorders by anti-tuberculosis medications.
First-line drug treatment for tuberculosis (TB) is frequently associated with liver toxicity. The goal of this study was to examine the association between UDP-glucuronosyl-transferase 1A1 (UGT1A1) genetic variations and anti-tuberculosis drug-induced hepatotoxicity (ATDH). A total of 98 patients, including 17 patients with ATDH, were enrolled; compound UGT1A1*27 and UGT1A1*28 were associated with an increased risk for developing ATDH after adjusting for age (OR 13.859; 95%CI 1.085-177.056). These findings require confirmation. However, screening for genetic variations prior to TB treatment may reduce the incidence of ATDH and improve treatment adherence.


Safety and Accuracy of Anatomic and Lateral Fluoroscopic-Guided Placement of C2 Pars/Pedicle Screws and C1 Lateral Mass Screws, and Freehand Placement of C2 Laminar Screws.
To evaluate the safety and accuracy of anatomic- and lateral fluoroscopic-guided placement of C2 pars/pedicle, C1 lateral mass screws, and freehand placement of C2 laminar screws. All the patients who underwent posterior cervical/occipitocervical fixation that involved the placement of C1/C2 screws during a 5-year period (2011-2015) at our institute were included in this study. C1/C2 screws were placed in a total of 94 patients during this period. A total of 97 C1 lateral mass, 49 C2 pars, 24 C2 pedicle, and 82 C2 laminar screws were placed in these patients. C1 lateral mass screws and C2 pars/pedicle screws were placed under anatomic and lateral fluoroscopic guidance. C2 laminar screws were placed by a freehand technique. The mean length (range) of various C2 screws was 16.4 ± 2.6 mm (12-22 mm) for pars screws, 18.8 ± 2.7 mm (14-24 mm) for pedicle screws, and 25.6 ± 3.4 mm (18-32 mm) for laminar screws. Postoperative CT imaging done in all patients before discharge revealed malposition of 2 laminar screws with breach of the inner cortex. The position of the remaining C1/C2 screws was perfect. The superior and medial angulation of the pars screws and superior angulation of the pedicle screws as measured in postoperative CT images were found to significantly deviate from the angles described in the literature. There was no mortality, vertebral artery injury, or neurologic injury related to C1/C2 screw placement in this series. Anatomic and lateral fluoroscopic-guided placement of C2 pars/pedicle screws and C1 lateral mass screws and freehand placement of C2 laminar screws is extremely safe.


Oscillometric blood pressure standards for children.
We previously reported blood pressure (BP) readings obtained by the Dinamap (DIN) (Model 8100) were 10 mmHg higher than those obtained by auscultatory methods and thus were not interchangeable. DIN BP data on 7208 schoolchildren ages 5 to 17 were analyzed to generate normative DIN BP standards and to examine the rational for presenting BP standards according to age and height percentiles. Three BP measurements were taken in the sitting position using a BP cuff width 40% to 50% of the circumference of the arm. Boys' systolic pressures (SP) were significantly (p < 0.05) greater (up to 11 mmHg) than those of the girls in subjects age 13 to 17 years. SP levels were most closely correlated with weight (r = 0.595), followed by height (r = 0.560) and age (r = 0.518). When BP levels were adjusted for age and weight, the correlation coefficient of DIN SP with height was negligible (r = 0.026 for boys; r = 0.085 for girls), whereas when adjusted for age and height, the correlation of SP with weight remained high (r = 0.303 for boys; r = 0.216 for girls), indicating that height is not an important independent predictor of BP levels. In conclusion, Dinamap-specific BP standards presented in this report are the only standards that have been generated according to the current BP guidelines recommended by national committees. We found no rational for presenting BP standards according to age and height percentiles.


Liver transplant center variability in accepting organ offers and its impact on patient survival.
Despite an allocation system designed to give deceased-donor livers to the sickest patients, many transplantable livers are declined by U.S. transplant centers. It is unknown whether centers vary in their propensities to decline organs for the highest priority patients, and how these decisions directly impact patient outcomes. We analyzed Organ Procurement and Transplantation Network (OPTN) data from 5/1/07-6/17/13, and included all adult liver-alone waitlist candidates offered an organ that was ultimately transplanted. We evaluated acceptance rates of liver offers for the highest ranked patients and their subsequent waitlist mortality. Of the 23,740 unique organ offers, 8882 (37.4%) were accepted for the first-ranked patient. Despite adjusting for organ quality and recipient severity of illness, transplant centers within and across geographic regions varied strikingly (p<0.001) in the percentage of organ offers they accepted for the highest priority patients. Among all patients ranked first on waitlists, the adjusted center-specific organ acceptance rates ranged from 15.7% to 58.1%. In multivariable models, there was a 27% increased odds of waitlist mortality for every 5% absolute decrease in a center's adjusted organ offer acceptance rate (adjusted OR: 1.27, 95% CI: 1.20-1.32). However, the absolute difference in median 5-year adjusted graft survival was 4% between livers accepted for the first-ranked patient, compared to those declined and transplanted at a lower position. There is marked variability in center practices regarding accepting livers allocated to the highest priority patients. Center-level decisions to decline organs substantially increased patients' odds of dying on the waitlist without a transplant.


LC-MS-MS identification of albendazole and flubendazole metabolites formed ex vivo by Haemonchus contortus.
Resistance of helminth parasites to common anthelminthics is a problem of increasing importance. The full mechanism of resistance development is still not thoroughly elucidated. There is also limited information about helminth enzymes involved in metabolism of anthelminthics. Identification of the metabolites formed by parasitic helminths can serve to specify which enzymes take part in biotransformation of anthelminthics and may participate in resistance development. The aim of our work was to identify the metabolic pathways of the anthelminthic drugs albendazole (ABZ) and flubendazole (FLU) in Haemonchus contortus, a world-wide distributed helminth parasite of ruminants. ABZ and FLU are benzimidazole anthelminthics commonly used in parasitoses treatment. In our ex vivo study one hundred living adults of H. contortus, obtained from the abomasum of an experimentally infected lamb, were incubated in 5 mL RPMI-1640 medium with 10 micromol L(-1) benzimidazole drug (10% CO(2), 38 degrees C) for 24 h. The parasite bodies were then removed from the medium. After homogenization of the parasites, both parasite homogenates and medium from the incubation were separately extracted using solid-phase extraction. The extracts were analyzed by liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization (ESI) in positive-ion mode. The acquired data showed that H. contortus can metabolize ABZ via sulfoxidation and FLU via reduction of a carbonyl group. Albendazole sulfoxide (ABZSO) and reduced flubendazole (FLUR) were the only phase I metabolites detected. Concerning phase II of biotransformation, the formation of glucose conjugates of ABZ, FLU, and FLUR was observed. All metabolites mentioned were found in both parasite homogenates and medium from the incubation.


The Genetics of Colorectal Cancer.
The hereditary colorectal cancer syndromes comprise a heterogeneous group of conditions with varying cancer risks, gastrointestinal polyp types, nonmalignant findings, and inheritance patterns. Although each one is unique in its own right, these syndromes often have overlapping features, making diagnoses difficult in select cases. Obtaining accurate polyp history (histologic type, number, location, and age of onset), cancer history (location, type, and age of onset), and other nonmalignant features is imperative in determining the likely disease diagnosis and thereby the appropriate genetic tests for precise diagnosis in a timely fashion. This process often necessitates collaboration among surgical oncology team members and genetic counselors.


G protein-coupled receptor quantification using peptide group-specific enrichment combined with internal peptide standard reporter calibration.
The G protein-coupled receptor (GPCR) super-family comprises the largest and most diverse group of membrane receptors in eukaryotes. GPCRs are involved in a plethora of physiological functions in all kinds of tissues. Detailed knowledge about GPCR presence and expression levels in tissues can be very helpful for drug development as the majority of drugs are designed to modulate membrane receptors. Furthermore, it is known that many adverse drug effects result from GPCR interactions. However, very few satisfactory methods are currently available for the detection and quantification of GPCRs. The detection is complicated by their three-dimensional structure, their hydrophobic properties, and their localization in the plasma membrane with 7-trans-membrane domains and small cytosolic and extracellular domains. Due to these properties it is very difficult to generate specific antibodies directed against GPCRs for sandwich immunoassays and Western blot. We therefore designed an immunoaffinity- and mass spectrometry-based approach to analyze GPCR-specific signature peptides in tryptic digests in rat tissue lysates. The expression levels of four different GPCRs were determined using chemically labeled synthetic standard peptides. Here, we demonstrate for the first time, that peptide immunoaffinity MS-based methods can render a reliable and quantitative analysis of multi-membrane spanning receptor molecules.


[On the suitability of spectrophotometric analyses for the estimation of blood stain age (author's transl)].
The spectrophotometric methods of Kind et al. and Kleihauer et al. were checked by more than 900 experiments on 85 blood stains on different material (cotton, nyltest and paper) from native and citrate blood, aged at room temperature up to 5 years. As a result, the variation of values within one age-group exceeded the differences between the values of samples of different age. Therefore, both methods are thought to be unsuitable for the estimation of blood stain age in practical forensic medicine, although the general trend described by the above authors could be confirmed.


Heel quantitative ultrasound (QUS) predicts incident fractures independently of trabecular bone score (TBS), bone mineral density (BMD), and FRAX: the OsteoLaus Study.
This study aimed to better define the role of heel-QUS in fracture prediction. Our results showed that heel-QUS predicts fracture independently of FRAX, BMD, and TBS. This corroborates its use as a case finding/pre-screening tool in osteoporosis management. Quantitative ultrasound (QUS) characterizes bone tissue based on the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Heel-QUS predicts osteoporotic fractures independently of clinical risk factors (CRFs) and bone mineral density (BMD). We aimed to investigate whether (1) heel-QUS parameters predict major osteoporotic fractures (MOF) independently of the trabecular bone score (TBS) and (2) the change of heel-QUS parameters over 2.5 years is associated with fracture risk. One thousand three hundred forty-five postmenopausal women from the OsteoLaus cohort were followed up for 7 years. Heel-QUS (SOS, BUA, and stiffness index (SI)), DXA (BMD and TBS), and MOF were assessed every 2.5 years. Pearson's correlation and multivariable regression analyses were used to determine associations between QUS and DXA parameters and fracture incidence. During a mean follow-up of 6.7 years, 200 MOF were recorded. Fractured women were older, more treated with anti-osteoporosis medication; had lower QUS, BMD, and TBS; higher FRAX-CRF risk; and more prevalent fractures. TBS was significantly correlated with SOS (0.409) and SI (0.472). A decrease of one SD in SI, BUA or SOS increased the MOF risk by (OR(95%CI)) 1.43 (1.18-1.75), 1.19 (0.99-1.43), and 1.52 (1.26-1.84), respectively, after adjustment for FRAX-CRF, treatment, BMD, and TBS. We found no association between the change of QUS parameters in 2.5 years and incident MOF. Heel-QUS predicts fracture independently of FRAX, BMD, and TBS. Thus, QUS represents an important case finding/pre-screening tool in osteoporosis management. The change in QUS over time was not associated with future fractures, making it inappropriate for patient monitoring.


Reassignment of sense codons in vivo.
The genetic code maps one or more of the 61 sense codons onto a set of 20 canonical amino acids. Reassignment of sense codons to non-canonical amino acids in model organisms such as Escherichia coli has been achieved through manipulation of the cellular protein synthesis machinery. Specifically, control of amino acid pools, coupled with engineering of the aminoacyl-tRNA synthetase activity of the host, has enabled assignment of sense codons to a wide variety of non-canonical amino acids under conditions routinely used for expression of recombinant proteins. Codon reassignment is leading to important advances in protein engineering and bioorganic chemistry. Here we summarize some of those advances, and provide detailed protocols for codon reassignment.


Physiological and Transcriptomic Analyses of Escherichia coli Serotype O157:H7 in Response to Rhamnolipid Treatment.
Rhamnolipid (RL) can inhibit biofilm formation of Escherichia coli O157:H7, but the associated mechanism remains unknown. We here conducted comparative physiological and transcriptomic analyses of cultures treated with RL and untreated cultures to elucidate a potential mechanism by which RL may inhibit biofilm formation in E. coli O157:H7. Anti-biofilm assays showed that over 70% of the E. coli O157:H7 biofilm formation capacity was inhibited by treatment with 0.25-1 mg/mL of RL. Cellular-level physiological analysis revealed that a high concentration of RL significantly reduced outer membrane hydrophobicity. E. coli cell membrane integrity and permeability were also significantly affected by RL due to an increase in the release of lipopolysaccharide (LPS) from the cell membrane. Furthermore, transcriptomic profiling showed 2601 differentially expressed genes (1344 up-regulated and 1257 down-regulated) in cells treated with RL compared to untreated cells. Functional enrichment analysis indicated that RL treatment up-regulated biosynthetic genes responsible for LPS synthesis, outer membrane protein synthesis, and flagellar assembly, and down-regulated genes required for poly-N-acetyl-glucosamine biosynthesis and genes present in the locus of enterocyte effacement pathogenicity island. In summary, RL treatment inhibited E. coli O157:H7 biofilm formation by modifying key outer membrane surface properties and expression levels of adhesion genes.


Molecular modeling, synthesis and screening of some new 4-thiazolidinone derivatives with promising selective COX-2 inhibitory activity.
In order to develop new selective cyclooxygenase-2 inhibitors, a series of novel 2-aryl-3-(4-sulfamoyl/methylsulfonylphenylamino)-4-thiazolidinones were designed. Molecular modeling studies with COX-2 enzyme were performed by using MOE program. The designed compounds with reasonable binding modes and high docking scores were synthesized. Their COX-1/COX-2 inhibitory activities were evaluated in vitro, using NS-398 and indomethacine as reference compounds. Compounds possessing methyl group (3d and 4d) on the phenyl ring exhibited highly COX-2 inhibitory selectivity and potency.


Population distribution of histological types of lung cancer: epidemiologic aspects in Israel and review of the literature.
A nationwide study of lung cancer in Israel during 1968-70 demonstrated a low to moderate incidence in men and a high incidence in women, as compared with other countries. The sex ratio was relatively lower than expected. This discrepancy results from a low rate of squamous cell carcinoma in men and a high rate of adenocarcinoma in women, and is consistent with similar, previously observed trends in North American Jews from New York, Pittsburgh and Montreal. The literature relating to the relative frequencies of various histological subcategories of lung cancer is reviewed and the importance, for etiology and prognosis, of a separate assessment of each distinct cell-type entity is emphasized.


Identification and functional analysis of mitochondrial complex I assembly factor homologues in C. elegans.
The biogenesis of mitochondrial NADH:ubiquinone oxidoreductase (complex I) requires several assembly chaperones. These so-called complex I assembly factors have emerged as a new class of human disease genes. Here, we identified putative assembly factor homologues in Caenorhabditis elegans. We demonstrate that two candidates (C50B8.3/NUAF-1, homologue of NDUFAF1 and R07H5.3/NUAF-3, homologue of NDUFAF3) clearly affect complex I function. Assembly factor deficient worms were shorter, showed a diminished brood size and displayed reduced fat content. Our results suggest that mitochondrial complex I biogenesis is evolutionarily conserved. Moreover, Caenorhabditis elegans appears to be a promising model organism to study assembly factor related human diseases.


Letter of apology and notice of retraction.
Retraction of: Yazdan, P. Sem Cutan Med Surg. 2012 Dec;31(4):258-266 PMID: 21605090 [PubMed - indexed for MEDLINE].


Benefits of not smoking during pregnancy for non-Aboriginal women and their babies in New South Wales, Australia: a record linkage study.
Smoking rates among pregnant women in New South Wales (NSW) have plateaued at 8-9%. To inform relevant smoking reduction efforts, we aimed to quantify the benefits of not smoking during pregnancy for non-Aboriginal NSW mothers and their babies. The benefits of not smoking during pregnancy for NSW Aboriginal mothers have previously been described. These data are important inputs in modelling health and economic impacts of smoking cessation interventions. This population-based cohort study used linked-data from routinely collected data sets. Not smoking during pregnancy was the exposure of interest among all NSW non-Aboriginal women who became mothers of singleton babies in 2012-2016. Unadjusted and adjusted relative risks (aRR) were used to examine associations between not smoking during pregnancy and adverse outcomes including severe morbidity, inter-hospital transfer, perinatal death, preterm birth and small-for-gestational age. Population attributable fractions (PAFs) were calculated to quantify adverse perinatal outcomes avoided in the population if all mothers were non-smokers. Compared with babies born to mothers who smoked during pregnancy, babies born to non-smoking mothers had a lower risk of all adverse perinatal outcomes including perinatal death (aRR = 0.68, 95%CI 0.61-0.76), preterm birth (aRR = 0.58, 95%CI 0.56-0.61) and small-for-gestational age (aRR = 0.48, 95%CI 0.47-0.50). PAFs(%) were 3.9% for perinatal death, 5.6% for preterm birth and 7.3% for small-for-gestational-age. Compared with women who smoked during pregnancy (n = 36,518), those who did not smoke (n = 413,072) had a lower risk of suffering severe maternal morbidity (aRR = 0.87, 95%CI 0.81-0.93) and being transferred to another hospital (aRR = 0.92, 95%CI 0.86-0.99). Mothers who reported not smoking during pregnancy had a small reduction in their risk of morbidity and of being transferred to another hospital whilst their babies had substantially reduced risks of all adverse perinatal outcomes. Results have implications for clinician training, clinical care standards, and performance management.


Psychosocial morbidity of Graves' orbitopathy.
Ocular diseases markedly impair daily function. In Graves' orbitopathy (GO), an associated psychosocial burden is present due to disfiguring proptosis and/or diplopia, signs with significant impact on functional status and well-being. We have therefore surveyed and assessed the psychosocial morbidity of GO. A prospective controlled study on subjects with GO using internationally validated, self-reporting questionnaires. One hundred and two consecutive patients with varying degrees of severity and activity of GO. Measurements Emotional distress, coping styles and quality of life (QoL) were assessed by the Hospital Anxiety and Depression Scale, by a German adaptation of the Ways-of-Coping Checklist, and with the 36-item Short Form, respectively. Stressful events in the 6 months preceding diagnosis were registered with the Life Experience Survey. QoL findings were compared to German reference values, as well as to 102 age- and gender-matched patients, each with type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) and inflammatory bowel disease (IBD), respectively. Compared to the German reference population, all QoL scales were at a lower rate and were especially decreased in subjects with active and/or severe GO, orbital pain, diplopia and stressful life events. Compared to diabetics, psychosocial scales were considerably reduced in GO (z = -1 vs. 0.1, P < 0.001) and higher scores for depressive coping (2.32 vs. 1.71, P < 0.001) and trivializing (2.37 vs. 1.97, P < 0.006) were noted. In GO, depressive coping and trivializing were negatively correlated with the mental (r = -0.603 and r =-0.411, both P < 0.001) and physical (r = -0.487 and r = -0.354, both P < 0.001) components of QoL. Depressive coping also positively correlated with anxiety (r = 0.636) and depression (r = 0.590), respectively, both P < 0.001. Emotional distress noted in 46 subjects, mostly with active and severe GO, was associated with poor QoL. Anxiety and depression were present in 41 and 24 GO patients, respectively. The number of stressful events positively correlated with the scores of anxiety (r = 0.3335) and depression (r = 0.3178), both P = 0.001. Foremost emotional distress, but also diplopia, stressful events and depressive coping had a major impact on QoL (proportion of variance explained = 13.1%, P < 0.001, multiple regression analysis). More than 75% of the psychosocial impairment in GO (R2= 0.76, P < 0.001) was associated with seven variables only (e.g. depression and anxiety). Six months prior to GO onset, 74 patients experienced a mean of 4 (range 0-13) stressful life events. Subjects with optic neuropathy had more stressful events than those without nerve involvement (5.1 vs. 2.7, P = 0.0425). Psychosocial morbidity is present in severe and/or active GO, which negatively affects QoL. The patients are not only physically ill, they also exhibit emotional distress. Accompanying psychosomatic treatment is indicated among about half of all GO patients.


Efficient Synthesis of the Cyclopentanone Fragrances (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone and Magnolione.
This paper describes the selective syntheses of two cis-isomer enriched cyclopentanone fragrances: (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone (4 steps, 62% overall yield, 67% cis) and Magnolione® (5 steps, 60% overall yield, 55% cis). In addition, the asymmetric synthesis of (3aR,7aS)-5-methyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-one as well as (3a'R,7a'S)-5'-methyl-2',3',3a',4',7',7a'-hexahydrospiro[[1,3]dioxolane-2,1'-indene]) has been realized by an efficient kinetic resolution, which enables the selective synthesis of the 2S,3R-isomer-enriched 3 and 4.


Cellular preservation of musculoskeletal specializations in the Cretaceous bird Confuciusornis.
The hindlimb of theropod dinosaurs changed appreciably in the lineage leading to extant birds, becoming more 'crouched' in association with changes to body shape and gait dynamics. This postural evolution included anatomical changes of the foot and ankle, altering the moment arms and control of the muscles that manipulated the tarsometatarsus and digits, but the timing of these changes is unknown. Here, we report cellular-level preservation of tendon- and cartilage-like tissues from the lower hindlimb of Early Cretaceous Confuciusornis. The digital flexor tendons passed through cartilages, cartilaginous cristae and ridges on the plantar side of the distal tibiotarsus and proximal tarsometatarsus, as in extant birds. In particular, fibrocartilaginous and cartilaginous structures on the plantar surface of the ankle joint of Confuciusornis may indicate a more crouched hindlimb posture. Recognition of these specialized soft tissues in Confuciusornis is enabled by our combination of imaging and chemical analyses applied to an exceptionally preserved fossil.


A new perspective on the evolutionary history of western European Sorex araneus group revealed by paternal and maternal molecular markers.
The species of the common shrew (Sorex araneus) group are morphologically very similar, but have undergone a spectacular chromosomal evolution. We investigate here the evolutionary history of the Sorex araneus group distributed in western Europe. In particular, we clarify the position of a difficult species, S. granarius, using sex-specific (mtDNA and Y-chromosome) markers. The karyotype of S. granarius is generally considered similar to the common ancestor of the restricted group considered here. The mtDNA data (1.4 kb) confirms the close relationship between S. granarius and S. araneus sensu stricto (hereafter S. araneus s.s.), but the Y-chromosome (3.4 kb) produces a quite different picture: S. granarius is closely related to another species, S. coronatus. Comparison of mtDNA and Y-chromosome phylogenies suggests that the genetic and chromosomal evolution in this group are disconnected processes. The evolutionary history of the south-western European populations of the S. araneus group can only be understood considering secondary contacts between taxa after their divergence, implying genetic exchanges by means of hybridization and/or introgression.


The mechanism of a formaldehyde-sensing transcriptional regulator.
Most organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. Therefore, biology has evolved systems to perceive and detoxify formaldehyde. The frmRA(B) operon that is present in many bacteria represents one such system. The FrmR protein is a transcriptional repressor that is specifically inactivated in the presence of formaldehyde, permitting expression of the formaldehyde detoxification machinery (FrmA and FrmB, when the latter is present). The X-ray structure of the formaldehyde-treated Escherichia coli FrmR (EcFrmR) protein reveals the formation of methylene bridges that link adjacent Pro2 and Cys35 residues in the EcFrmR tetramer. Methylene bridge formation has profound effects on the pattern of surface charge of EcFrmR and combined with biochemical/biophysical data suggests a mechanistic model for formaldehyde-sensing and derepression of frmRA(B) expression in numerous bacterial species.


Effect of resovist on rats with different severities of liver cirrhosis.
Whether the degree of diffuse hepatic damage is correlated with the signal change on MR images after injection of superparamagnetic iron oxide (SPIO) particles was investigated. In addition, we investigated whether hepatic function deteriorates after injection of SPIO. Seventy-six female Sprague-Dawley rats aged 3 to 4 weeks were given drinking water containing 0.03% thioacetamide (TAA) for 4 or 12 weeks to induce two grades of liver injury. Seventeen normal rats were served as a control. Normal and model rats were administered Resovist (10 micromol Fe/kg), and signal intensities in the liver on MR images obtained at 4.7 T were measured up to 60 minutes after injection (n = 5). The model rats were injected with 10 times the envisaged dose of Resovist (100 micromol Fe/kg) or saline as a control substance, and blood parameters were measured at 4, 24, and 48 hours after injection (n = 5 or 6). At 4 hours after injection, iron and Kupffer cells in the liver were stained (n = 3). Maximal signal reduction in the liver occurred 15 minutes after injection in all groups. The reduced signal persisted for 60 minutes after injection. However, the degree of maximal signal reduction in the model rats was significantly less than that in the normal rats (P < 0.05, 0.01). Signal reduction in the 12-week group was less than that in the 4-week group. In control rats, the number of iron-positive cells increased by 22 cells per area (0.065 mm(2)) following treatment with Resovist. In the 4-week and 12-week groups, numbers of iron-positive cells increased by 13 and 11 cells, respectively. There was no statistically significant difference in the number of Kupffer cells between control and model rats. No significant change was observed in blood parameters with Resovist. The MR signal induced by Resovist depended on the degree of phagocytic activity in the liver. The safety profiles of Resovist remained unchanged even at 10 times the imaging dose.


Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents.
A low level of response to alcohol has been associated with both the genetic constitution of the regulatory region (SLC6A4) of the human serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) and with future alcohol intake and an increased risk for alcoholism. To date, all studies of relevant polymorphisms have been carried out in populations in the United States. Data were extracted from a subset (n = 243) of a cohort of children who have been observed since birth through evaluation of the family history of alcoholism and psychosocial risk influences. At age 16 years, the response to alcohol was assessed with the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and the average amount of alcohol intake per month was assessed during the prior 6 months. Additional variables that were measured included the 5-HTT genotype, externalizing behavior, and sociodemographic variables, such as gender and age. The level of response to alcohol was significantly lower among carriers of two long alleles of the 5-HTT regulatory region compared with carriers of one or two short alleles (Mann-Whitney U = 5225.0, p = .005). In a multiple regression analysis, the level of response to alcohol and externalizing behavior but not psychosocial factors significantly predicted the average amount of alcohol intake per month. This study demonstrates that, independent of the assessed psychosocial variables, the 5-HTT genotype correlated with the level of response to alcohol and predicted alcohol intake among 16-year-old adolescents.


Autonomous sensory meridian response: Your patients already know, do you?
Public interest in autonomous sensory meridian response (ASMR) is growing on digital media platforms. Some people can elicit the response by watching videos containing triggering sounds and images. People susceptible to ASMR's effects report tingling sensations on the head and neck, as well as feelings of euphoria, relaxation, and mood elevation. Underlying mechanisms of the phenomenon are not well understood, but physiologic evidence corroborates some of the self-reported positive effects. Healthcare professionals should be aware of this emerging topic, and the potential for therapeutic applications should be investigated.


The domino blocks: a simple solution for parallel solid-phase organic synthesis.
The domino block is a reaction block for manual and semi-automatic parallel solid-phase organic synthesis that simplifies liquid exchange and integrates common synthetic steps. The domino block consists of enclosed reaction vessels, polypropylene syringes, attached to a manifold that clamps the syringes and connects them to a common port. Liquid is removed from the closed reaction vessels by vacuum connected to the common port. The vacuum formed inside each reaction vessel is subsequently used to draw fresh solvent or reagent into each reaction vessel.


Feasibility and results of an intensive cardiac rehabilitation program. Insights from the MxM (Más por Menos) randomized trial.
Cardiac rehabilitation programs (CRP) are a set of interventions to improve the prognosis of cardiovascular disease by influencing patients' physical, mental, and social conditions. However, there are no studies evaluating the optimal duration of these programs. We aimed to compare the results of a standard vs a brief intensive CRP in patients after ST-segment elevation and non-ST-segment elevation acute coronary syndrome through the Más por Menos study (More Intensive Cardiac Rehabilitation Programs in Less Time). In this prospective, randomized, open, evaluator-blind for end-point, and multicenter trial (PROBE design), patients were randomly allocated to either standard 8-week CRP or intensive 2-week CRP with booster sessions. A final visit was performed 12 months later, after completion of the program. We assessed adherence to the Mediterranean diet, psychological status, smoking, drug therapy, functional capacity, quality of life, cardiometabolic and anthropometric parameters, cardiovascular events, and all-cause mortality during follow-up. A total of 497 patients (mean age, 57.8±10.0 years; 87.3% men) were finally assessed (intensive: n=262; standard: n=235). Baseline characteristics were similar between the 2 groups. At 12 months, the results of treadmill ergometry improved by ≥ 1 MET in ≥ 93% of the patients. In addition, adherence to the Mediterranean diet and quality of life were significantly improved by CRP, with no significant differences between the groups. The occurrence of cardiovascular events was similar in the 2 groups. Intensive CRP could be as effective as standard CRP in achieving adherence to recommended secondary prevention measures after acute coronary syndrome and could be an alternative for some patients and centers. Registered at ClinicalTrials.gov (Identifier: NCT02619422).


PCA: prostate cancer, patient-centred approach or both?
What's known on the subject? and What does the study add? Several studies have explored patient-specific expectations of prostate cancer management, while others have investigated physicians' perceptions. However, the opinions of both groups have seldom been compared in one study. Therefore, the present study compares the results of two surveys, one among physicians and one among patients, on patient-physician communication and patients' expectations of prostate cancer management. The present review aims to highlight the differences and similarities in opinion on prostate cancer management between physicians and patients. It reflects the most important results of two surveys on patient-specific expectations in prostate cancer management, done among European prostate cancer specialists and patients with prostate cancer. These results are compared with published data. In addition, the authors' opinion on the survey results and on optimal prostate cancer management is included. To evaluate differences and similarities in opinions on and expectations of prostate cancer management between physicians and patients. Two surveys on patient-specific opinions and expectations in prostate cancer management were done in 2011 among European prostate cancer specialists and patients with prostate cancer. Survey results were complemented with existing published data and with the authors' opinion. Most specialists spent 15-29 min on delivering the diagnosis, and about the same amount of time on explaining treatment options. This time was considered insufficient by 35% and 48% of patients, respectively. There was a large discrepancy between physicians' and patients' opinions about the type of provided prognostic and therapeutic information, indicating that patients may not have completely understood this information. Shared decision-making was preferred by both patients and specialists. Treatment efficacy was the most important factor determining treatment choice for both groups, while the physician's opinion or experience also had a great impact on patients' treatment choice. Patient-support groups have an important role in providing relevant information and in exchanging experiences between patients. The supportive role of partners/relatives was more appreciated when discussing treatment options than during diagnosis. Although patients' expectations are generally matched by their caring physician(s), physicians can still improve quality of care by taking adequate time for their patients, by using terminology that is easily understood by patients and by encouraging shared decision-making. A multidisciplinary team may be an important part of the treatment paradigm, with the individual patient's needs and preferences as the centre of care.


Expanding the Criteria for Nipple-Sparing Mastectomy in Patients With Poor Prognostic Features.
In this study we aimed to review the outcomes of nipple-sparing mastectomy (NSM) in the setting of expanded criteria: previous breast surgery/irradiation, neoadjuvant chemotherapy (NAC), post-NSM irradiation, and to assess conversion to acceptable criteria after NAC. In this single-institution institutional review board-approved retrospective review, we identified patients who underwent NSM after previous breast intervention or NAC from January 2010 to February 2017. Clinicopathologic features, previous breast surgeries, response rate, complications, and recurrences were recorded. Sixty-three patients underwent 106 NSMs. Among 63 patients, 39 (61.9%) received NAC, 30 (47.6%) previous lumpectomy, 4 (6.3%) with cosmetic implants, 4 (6.3%) with mastopexy, 5 (7.9%) with previous radiation therapy, and 21 (33%) underwent post-NSM radiation therapy. Transient epidermolysis occurred in 24 patients (38.1%), with 16 patients (66.6%) having complete flap recovery and nipple loss in 8 patients (12.6%). All 10 patients with central disease on pre-NAC imaging converted to acceptable criteria, with 9 having successful NSM. At mean 67.2-month follow-up, 56 patients (88.9%) were disease-free, 5 (7.9%) experienced a systemic recurrence, and 2 (3.2%) a local recurrence. NSM is oncologically acceptable in this patient cohort. Patients with large central tumors who undergo NAC should be reconsidered after completion of chemotherapy because many might convert to successful nipple-areolar preservation.


Carcinogenic and non-carcinogenic risk of exposure to metal fume in different types of welding processes.
The international agency for cancer research (IARC) has classified welding fumes as definitive carcinogens. The aim of the present study was to assess health risk due to exposure to welding fumes in different welding types. In this study, exposure to fumes of iron (Fe), chromium (Cr), and nickel (Ni) in the breathing zone air of 31 welder engaged in arc, argon and CO2 welding was assessed. Carcinogenic and non-carcinogenic risk assessments due to exposure to fumes were performed using the method proposed by the Environmental Protection Agency (EPA) by Monte Carlo simulation. The results showed that in the CO2 welding, concentration of Ni, Cr, and Fe was lower than the 8-h Time-Weighted Average Threshold Limit Value (TWA-TLV), recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). In argon welding, Cr and Fe concentrations were higher than the TWA-TLV. In arc welding, concentrations of Ni and Fe were more than the TWA-TLV. In addition, the risk of non-carcinogenicity due to exposure to Ni and Fe in all three types of welding was more than standard level (HQ>1). The results indicated that the welders are at health risk due to exposure to metal fumes. Preventive exposure control measures such as local ventilation need to be implemented in welding workplaces.


Regulatory functions of protein multisite phosphorylation.
In recent years it has become apparent that an increasing number of proteins can be phosphorylated at several different sites. In this article protein multisite phosphorylation is discussed with reference to the enzymes glycogen synthase, pyruvate dehydrogenase, and phosphorylase kinase. Each of these enzymes contains three or more different phosphorylation sites on one or more subunits. Activation and inactivation of the enzymes appear to correlate quite well with phosphorylation of a few key sites on the protein. The other phosphorylation sites may influence other kinetic properties of the enzymes or regulate the rates of dephosphorylation of the key sites by the appropriate phosphatase. Thus, multisite phosphorylation may represent an important mechanism for regulating several functions of complex proteins.


Spontaneous remission of angioimmunoblastic T-cell lymphoma in a child with ataxia-telangiectasia: a case report.
Angioimmunoblastic T-cell lymphoma is an uncommon subtype of peripheral T-cell lymphoma in children with fewer than 20 cases reported in literature. A 3-year-old Omani boy was diagnosed with ataxia-talengectasia presenting with fever and generalized lymphadenopathy. His biopsy revealed atypical lymphocytic infiltrate consistent with the diagnosis of angioimmunoblastic T-cell lymphoma. Within 3 weeks from the initial presentation and without any neoadjuvant therapy, he showed complete recovery of symptoms with absence of fever and regression of all previously affected lymph nodes. He has remained in remission ever since. This is the first report of spontaneous improvement of angioimmunoblastic T-cell lymphoma in a patient with ataxia-telangiectasia who was 3 years old at presentation. Owing to the paucity of similar cases, this report adds valuable diagnostic, therapeutic, and monitoring data.


Induced oligomerization targets Golgi proteins for degradation in lysosomes.
Manganese protects cells against forms of Shiga toxin by down-regulating the cycling Golgi protein GPP130. Down-regulation occurs when Mn binding causes GPP130 to oligomerize and traffic to lysosomes. To determine how GPP130 is redirected to lysosomes, we tested the role of GGA1 and clathrin, which mediate sorting in the canonical Golgi-to-lysosome pathway. GPP130 oligomerization was induced using either Mn or a self-interacting version of the FKBP domain. Inhibition of GGA1 or clathrin specifically blocked GPP130 redistribution, suggesting recognition of the aggregated GPP130 by the GGA1/clathrin-sorting complex. Unexpectedly, however, GPP130's cytoplasmic domain was not required, and redistribution also occurred after removal of GPP130 sequences needed for its normal cycling. Therefore, to test whether aggregate recognition might be a general phenomenon rather than one involving a specific GPP130 determinant, we induced homo-oligomerization of two unrelated Golgi-targeted constructs using the FKBP strategy. These were targeted to the cis- and trans-Golgi, respectively, using domains from mannosidase-1 and galactosyltransferase. Significantly, upon oligomerization, each redistributed to peripheral punctae and was degraded. This occurred in the absence of detectable UPR activation. These findings suggest the unexpected presence of quality control in the Golgi that recognizes aggregated Golgi proteins and targets them for degradation in lysosomes.


A validated clinical tool for the prediction of varices in PBC: the Newcastle Varices in PBC Score.
Gastro-oesophageal varices (GOV) can occur in early stage primary biliary cirrhosis (PBC), making it difficult to identify the appropriate time to begin screening with oesophageo-gastro-duodenoscopy (OGD). Our aim was to develop and validate a clinical tool to predict the probability of finding GOV in PBC patients. A cross-sectional retrospective study analysing clinical data of 330 PBC patients who underwent an OGD at the Freeman Hospital, Newcastle was used to create a predictive tool, the Newcastle Varices in PBC (NVP) Score, that was externally validated in PBC patients from Cambridge (UK) and Toronto (Canada). 48% of the Newcastle, 31% of the Cambridge, and 22% of the Toronto cohorts of PBC patients had GOV. Twenty-five percent (95% CI 18-32%) of the Newcastle cohort had GOV diagnosed at an index variceal bleed. Of the others, 37% (95% CI 28-46%) bled after a median of 1.5 years (IQR 3.75). Transplant-free survival was significantly better in those without GOV than in those with GOV (p<0.001), but similar in patients with GOV that bled and those that did not (p=0.1). The NVP score (%Probability)=1/[1+exp^-(9.186+0.001*alkaline phosphatase in IU-0.178*albumin in g/L-0.015*platelet × 10(9)) was validated in 2 external cohorts and was highly discriminant (AUROC 0.86). Cost consequences analyses revealed the NVP score to be as accurate as, but more economical than using either OGD directly or other risk scores for screening PBC patients. The NVP score is an inexpensive, non-invasive, externally validated tool that accurately predicts GOV in PBC.


Self-mutilation in substance-dependent patients and relationship with childhood abuse and neglect, alexithymia and temperament and character dimensions of personality.
Aim of this study was to evaluate the prevalence of self-mutilation (SM) in Turkish male substance-dependent patients, and to investigate the relationship of SM with childhood abuse and neglect, alexithymia and temperament and character dimensions of personality. Participants were 136 consecutively admitted males with substance dependence (96 alcohol and 40 drug). Substance dependence was diagnosed by means of the Structured Clinical Interview for DSM-IV (SCID-I), Turkish version. Patients were investigated with the childhood abuse and neglect questionnaire, Toronto alexithymia scale (TAS-20) and temperament and character inventory (TCI). Among substance-dependent patients 34.6% was considered as a group with SM. Rates of being single and unemployed, histories of physical and sexual abuse and suicide attempts were higher in the SM group. Current age, age at first substance use and age at regular substance use were lower in the group with SM. Mean of TAS-20 and 'difficulty in identifying feelings' (DIF) and 'difficulty in describing feelings' (DDF) subscales of TAS-20 were higher in SM group. There were no significant differences between groups in terms of TCI subscales. Age, childhood physical abuse and suicide attempt history predicted SM in logistic regression. Young substance users with childhood physical abuse histories could be the target population to prevent self-mutilating behavior. This study also suggests that whenever self-mutilating behavior is present, the possibility of childhood abuse, alexithymia and suicide attempts must be evaluated.


Mechanistic insights into poly(C)-binding protein hnRNP K resolving i-motif DNA secondary structures.
I-motifs are four-strand noncanonical secondary structures formed by cytosine (C)-rich sequences in living cells. The structural dynamics of i-motifs play essential roles in many cellular processes, such as telomerase inhibition, DNA replication, and transcriptional regulation. In cells, the structural dynamics of the i-motif can be modulated by the interaction of poly(C)-binding proteins (PCBPs), and the interaction is closely related to human health, through modulating the transcription of oncogenes and telomere stability. Therefore, the mechanisms of how PCBPs interact with i-motif structures are fundamentally important. However, the underlying mechanisms remain elusive. I-motif structures in the promoter of the c-MYC oncogene can be unfolded by heterogeneous nuclear ribonucleoprotein K (hnRNP K), a PCBP, to activate its transcription. Here, we selected this system as an example to comprehensively study the unfolding mechanisms. We found that the promoter sequence containing 5 C-runs preferred folding into type-1245 to type-1234 i-motif structures based on their folding stability, which was further confirmed by single-molecule FRET. In addition, we first revealed that the c-MYC i-motif structure was discretely resolved by hnRNP K through two intermediate states, which were assigned to the opposite hairpin and neighboring hairpin, as further confirmed by site mutations. Furthermore, we found all three KH (hnRNP K homology) domains of hnRNP K could unfold the c-MYC i-motif structure, and KH2 and KH3 were more active than KH1. In conclusion, this study may deepen our understanding of the interactions between i-motifs and PCBPs and may be helpful for drug development.


An experimental murine model to study periodontitis.
Periodontal disease (PD) is a common dental disease associated with the interaction between dysbiotic oral microbiota and host immunity. It is a prevalent disease, resulting in loss of gingival tissue, periodontal ligament, cementum and alveolar bone. PD is a major form of tooth loss in the adult population. Experimental animal models have enabled the study of PD pathogenesis and are used to test new therapeutic approaches for treating the disease. The ligature-induced periodontitis model has several advantages as compared with other models, including rapid disease induction, predictable bone loss and the capacity to study periodontal tissue and alveolar bone regeneration because the model is established within the periodontal apparatus. Although mice are the most convenient and versatile animal models used in research, ligature-induced periodontitis has been more frequently used in large animals. This is mostly due to the technical challenges involved in consistently placing ligatures around murine teeth. To reduce the technical challenge associated with the traditional ligature model, we previously developed a simplified method to easily install a bacterially retentive ligature between two molars for inducing periodontitis. In this protocol, we provide detailed instructions for placement of the ligature and demonstrate how the model can be used to evaluate gingival tissue inflammation and alveolar bone loss over a period of 18 d after ligature placement. This model can also be used on germ-free mice to investigate the role of human oral bacteria in periodontitis in vivo. In conclusion, this protocol enables the mechanistic study of the pathogenesis of periodontitis in vivo.


Frequency of turning in bed at home in persons with chronic spinal cord injury.
Objective: To determine the routine turning frequency of persons with chronic spinal cord injury (SCI) in bed at night in their home environment.Design: An online questionnaire consisting of 22 questions.Setting: Free standing SCI rehabilitation facility.Participants: Persons between ages 18-75 with a traumatic SCI for ≥3 months, and living at home.Interventions: None.Outcome measures: Questionnaire-based evaluation of turning frequency of persons with SCI.Results: 86 subjects (70 men) with traumatic SCI completed the survey; 66.3% with tetraplegia and 41.9% with a neurological complete SCI. Almost every participant (96%) recalled being counseled on the importance of turning in bed at night upon discharge from their rehabilitation facility with 48.4% recalling the frequency recommended as every 2 h. At present, 25.6% of subjects reported turning every 2 h, 15.1% every 3 h, 15.1% every 4 h, 3.5% every 6 h, and 40.7% of respondents stated that they do not turn regularly at night.Conclusion: Although frequently recommended for repositioning at night in bed every two hours for persons with chronic SCI, especially for those at risk for pressure injuries, only 25.6% of individuals report turning at this frequency and 40.7% report not turning at night time regularly. The reasons for limited turning may be multi-factorial, however, this finding may serve as a call to practitioners to best determine the most appropriate turning frequency that can meet compliance of the individual with SCI, as well as maintain skin protection in the chronic period after injury.


Inflammatory markers predict late cardiac events in patients who are exhausted after percutaneous coronary intervention.
Chronic inflammation is one of the main underlying mechanisms in the development of coronary artery disease (CAD). We investigated the prognostic value of inflammatory markers for cardiac events occurring more than 6 months after percutaneous coronary intervention (PCI), i.e. late cardiac events, furthermore we investigated the temporal stability of these markers. Exhausted patients (234) recently treated by successful PCI were studied. Serum samples collected about 6 weeks after PCI (baseline), 6 and 18 months after baseline were analyzed for CRP, IL-6, tumour necrosis factor (TNF-alpha), IL-10, IL-1ra, IL-8 and neopterin. In the mean cardiac follow-up of 24 months, 25 late cardiac events occurred. Cox proportional hazards analysis was used to determine the prognostic value. Elevated concentrations of IL-6 at baseline and 6 months later increased the risk of late cardiac events (RR 3.9, CI 1.7-9.0, p 0.00 and RR 3.6, CI 1.6-8.5, p 0.00). Elevated concentrations of CRP and IL-10 at baseline also increased the risk of late cardiac events (RR 2.5, CI 1.1-5.7, p 0.04 and RR 2.5, CI 1.1-5.6, p 0.03) as did IL-1 receptor antagonist at 6 months (RR 2.6, CI 1.1-6.1, p 0.04). Temporal stability was high for most markers, but highest for IL-6. These results support the assumption that chronic inflammation is a pathophysiological mechanism in the development of CAD.


Transaortic Chordal Cutting: Mitral Valve Repair for Obstructive Hypertrophic Cardiomyopathy With Mild Septal Hypertrophy.
In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) and mild septal hypertrophy, mitral valve (MV) abnormalities may play an important role in MV displacement into the left ventricular (LV) outflow tract. Therefore, isolated myectomy may not relieve outflow obstruction and symptoms, and MV replacement is often the surgical alternative. This study sought to assess the clinical and hemodynamic results of cutting thickened secondary MV chordae combined with a shallow septal muscular resection in severely symptomatic patients with obstructive HCM and mild septal hypertrophy. Clinical features were compared before surgery and at most recent clinical evaluation in 39 consecutive patients with obstructive HCM. Over a 23 ± 2 months follow-up, New York Heart Association functional class decreased from 2.9 ± 0.5 pre-operatively to 1.1 ± 1.1 post-operatively (p < 0.001), with no patient in class III at most recent evaluation. The resting outflow gradient decreased from 82 ± 43 mm Hg to 9 ± 5 mm Hg (p < 0.001) and septal thickness decreased from 17 ± 1 mm to 14 ± 2 mm (p < 0.001). No patient had MV prolapse or flail and 1 had residual moderate-to-severe MV regurgitation at most recent evaluation. MV geometry before and after surgery was compared with that of 25 consecutive patients with similar clinical profile and septal thickness that underwent isolated myectomy. After adjustment for differences in pre-operative values between the groups, the post-operative anterior MV leaflet-annulus ratio was 17% greater and tenting area 24% smaller in patients with chordal cutting, indicating that MV apparatus had moved to a more normal posterior position within the LV cavity, preventing MV systolic displacement into the outflow tract and outflow obstruction. This procedure relieves heart failure symptoms, abolishes LV outflow gradient, and avoids MV replacement in patients with obstructive HCM and mild septal thickness.


Relative growth rate and biomass allocation in ten woody species with different leaf longevity using phylogenetic independent contrasts (PICs).
In this study, we compare the relative growth rate (RGR) and biomass allocation of 10 woody species (5 deciduous and 5 evergreen) from the Mediterranean region using phylogenetic independent contrasts (PICs) to test if these two functional groups differ in these traits. In general, the results were similar when using PICs or without taking into account phylogenetic relations. Deciduous species had a higher RGR than evergreen species, due to the higher net assimilation rate (NAR). Deciduous species had a higher specific leaf area (SLA) but a lower leaf mass ratio (LMR), resulting in a similar LAR for deciduous and evergreen species (LAR = SLA x LMR). In some cases, the use of PICs revealed patterns that would not have appeared if phylogeny had been overlooked. For example, there was no significant correlation between RGR and final dry mass (after 4 months of growth) but PICs revealed that there was a positive relation between these two variables in all deciduous-evergreen pairs. In general, RGR decreased with time and this temporal variation was due primarily to NAR variations (r = 0.79, p < 0.01), and also to variations in LAR (r = 0.69, p < 0.05). Considering the phylogeny, the only variable constantly different for all deciduous-evergreen pairs was SLA. This result, and the fact that SLA was the best correlated variable with RGR (r = 0.81, p < 0.01), reinforce the value of SLA as a variable closely associated to growth and to the functional groups (deciduous vs. evergreen).


Inhibitory effect of HGF on invasiveness of aggressive MDA-MB231 breast carcinoma cells, and role of HDACs.
Hepatocyte growth factor (HGF), through Met receptor binding, fulfils numerous functions in invasive tumour growth (survival/proliferation, motility, apoptosis), but epigenetic control of gene expression in this process is poorly understood. In HGF-treated breast cancer cells we studied (a) the chemoinvasion towards CXCL12 (ligand of the chemokine-receptor CXCR4) and (b) the mechanistic basis, that is, the transduction pathways that regulate CXCR4-mediated invasion, and the role played by histone deacetylases (HDACs) after blockade with trichostatin A (TSA). In highly invasive and metastatic MDA-MB231 cells HGF had a dual inhibitory effect, reducing spontaneous migration and specific chemoinvasion towards CXCL12, the latter by decreasing CXCR4 transactivation and protein level. After HGF the levels of phosphorylated (therefore active) c-Src and Akt persistently increased, indicating a role of these signal transducers in the HGF-dependent cellular and molecular effects. c-Src wild-type expression vector (Srcwt) increased active c-Src and mimicked the HGF-dependent inhibition of CXCR4 transactivation. Our findings indicate that HDACs participated in the HGF-inhibitory effects. In fact, blockade of HDACs hindered the HGF- and Srcwt-dependent reductions of CXCR4 transactivation and invasiveness, while inhibition of endogenous c-Src was additive with HGF, further reducing specific chemoinvasion. In conclusion, in MDA-MB231 cells HDAC blockade with TSA partly counteracted the HGF-dependent effects through molecular events that included enhancement of the expression of the genes for invasiveness Met and CXCR4 (depending on serum conditions), reduction of endogenous phospho-c-Src/c-Src and phosphoAkt/Akt ratios and triggering of apoptosis. The potential therapeutic use of TSA should take into account the variable aggressiveness of breast carcinoma cells and microenvironment signals such as HGF at the secondary growth site of the tumour. It was interesting that HGF reduced motility and CXCR4 functionality only of MDA-MB231 cells, and not of low-invasive MCF-7 cells, suggesting a mechanism implicated in metastatic cell homing.


[Video games, a therapeutic mediator for teens].
Teenagers love video games and other multimedia tools. Sometimes they love them too much, leading to addictive use. A child psychiatry team in Nancy has developed a therapeutic multimedia workshop to contribute to treating teens.


Phoma herbarum, a soil fungus able to grow on natural lignin and synthetic lignin (DHP) as sole carbon source and cause lignin degradation.
The fungus Phoma herbarum isolated from soil showed growth on highly pure lignin extracted from spruce wood and on synthetic lignin (DHP). The lignin remaining after cultivation was shown to have a lower molecular weight. The reduction in the numbers of ether linkages of the extracted lignins was also observed by derivatization followed by reductive cleavage (DFRC) in combination with (31)P NMR studies. The fungal strain showed an ability to degrade synthetic lignin by extracellular catalysts. GC-MS was applied to study the evolution of low molar mass adducts, e.g., monolignols and it was shown that a reduced coniferyl alcohol product was produced from DHP in a cell-free environment. The work has demonstrated the ability of soil microbes to grow on lignin as sole carbon source. The potential impact is in the production of low molar mass renewable phenols for material application.