Greenspace use during the COVID-19 pandemic: A longitudinal population mobility study in the United Kingdom.
The coronavirus pandemic greatly disrupted the lives of people. Restrictions introduced worldwide to limit the spread of infection included stay-at-home orders, closure of venues, restrictions to travel and limits to social contacts. During this time, parks and outdoor greenspaces gained prominent attention as alternative location for respite. Population mobility data offers a unique opportunity to understand the impact of the pandemic on outdoor behaviour. We examine the role of the restrictions on park use throughout the full span of the pandemic while controlling for weather and region. This study provides a longitudinal population analysis of park visitation using Google COVID-19 Community Mobility Reports data in the UK. Daily park visitation was plotted and ANOVA analyses tested season and year effects in visitation. Then, regressions examined park visitation beyond weather (temperature and rain), according to COVID-19 restrictions, while controlling for region specificities through unit fixed effect models. Time series and ANOVA analyses documented the significant decrease in park visitation in the spring of 2020, the seasonal pattern in visitation, and an overall sustained and elevated use over nearly three years. Regressions confirmed park visitation increased significantly when temperature was greater and when it rained less. More visitation was also seen when there were fewer COVID-19 cases and when the stringency level of restrictions was lower. Of special interest, a significant interaction effect was found between temperature and stringency, with stringency significantly supressing the effect of higher temperature on visitation. COVID-19 restrictions negatively impacted park visitation on warm days. Given the general health, social, and wellbeing benefits of greenspace use, one should consider the collateral negative impact of restrictions on park visitation. When social distancing of contacts is required, the few remaining locations where it can safely occur should instead be promoted.


MECHANISMS IN ENDOCRINOLOGY: Genetics of human bone formation.
Throughout life, bone is continuously remodelled to be able to fulfil its multiple functions. The importance of strictly regulating the bone remodelling process, which is defined by the sequential actions of osteoclasts and osteoblasts, is shown by a variety of disorders with abnormalities in bone mass and strength. The best known and most common example of such a disorder is osteoporosis, which is marked by a decreased bone mass and strength that consequently results in an increased fracture risk. As osteoporosis is a serious health problem, a large number of studies focus on elucidating the aetiology of the disease as well as on the identification of novel therapeutic targets for the treatment of osteoporotic patients. These studies have demonstrated that a large amount of variation in bone mass and strength is often influenced by genetic variation in genes encoding important regulators of bone homeostasis. Throughout the years, studies into the genetic causes of osteoporosis as well as several rare monogenic disorders with abnormal high or low bone mass and strength have largely increased the knowledge on regulatory pathways important for bone resorption and formation. This review gives an overview of genes and pathways that are important for the regulation of bone formation and that are identified through their involvement in monogenic and complex disorders with abnormal bone mass. Furthermore, novel bone-forming strategies for the treatment of osteoporosis that resulted from these discoveries, such as antibodies against sclerostin, are discussed as well.


Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats.
We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.


β1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats.
Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts.


Views of breastfeeding difficulties among drop-in-clinic attendees.
Breast-milk is the optimum form of nutrition for the first 6 months of life. However, breastfeeding rates in the UK are low and static compared to other European countries and those in the North-west of England in the UK are even lower. Of the women who initiate breastfeeding, many cease in the first month following the birth for reasons that might be avoided. To try and prevent this, UNICEF Baby Friendly Hospital Initiative (BFHI) 'Ten Steps to Successful Breastfeeding' state that maternity facilities should foster the development of support groups for breastfeeding women. The aim of the present study was to describe breastfeeding difficulties reported by women who attended the infant feeding clinic at a Women's Hospital in the North-west of England. During the study period, the clinic was attended mainly by primiparous mothers who were educated beyond 18 years of age and of higher socio-economic status. They presented with a variety of problems including baby not latching on, concerns about baby's weight gain/loss, sore nipples and advice about expressing milk in preparation for return to work. The women highlighted the importance of meeting other mothers and having someone to talk to who understood what they were going through. Inconsistent information/lack of detailed knowledge from health professionals was cited as contributing to breastfeeding difficulties. A number of women reported that expert hands-on, one-to-one support, was invaluable and many felt they were able to continue breastfeeding but without the support, they may have given up.


Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer's Disease.
Alzheimer's disease (AD) is a brain disorder that progressively undermines memory and thinking skills by affecting the hippocampus and entorhinal cortex. The main histopathological hallmarks of AD are the presence of abnormal protein aggregates (Aβ and tau), synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. However, oxidative stress or oxidative damage is also evident and commonly overlooked or considered a consequence of the advancement of dementia symptoms. The control or onset of oxidative stress is linked to the activity of the amyloid-β peptide, which may serve as both antioxidant and pro-oxidant molecules. Furthermore, oxidative stress is correlated with oxidative damage to proteins, nucleic acids, and lipids in vulnerable cell populations, which ultimately lead to neuronal death through different molecular mechanisms. By recognizing oxidative stress as an integral feature of AD, alternative therapeutic or preventive interventions are developed and tested as potential or complementary therapies for this devastating neurodegenerative disease.


Chronic obstructive pulmonary disease and weaning of difficult-to-wean patients from mechanical ventilation: randomized prospective study.
To compare T-tube and pressure support ventilation (PSV) as two methods of mechanical ventilation weaning of patients with chronic obstructive pulmonary disease (COPD) after failed extubation. A prospective randomized trial carried out at the multidisciplinary intensive care unit (ICU) over 2 years included 136 patients with COPD who required mechanical ventilation longer than 24 hours. The patients who could be weaned from mechanical ventilation were randomized to either a T-tube or PSV 2-hour spontaneous breathing trial. The patients in whom 2-hour trial was successful were extubated and excluded from further research. Patients in whom 2-hour trial failed had mechanical ventilation reinstated and underwent the same weaning procedure after 24 hours in case they fulfilled the weaning criteria. The weaning outcome was assessed according to the following parameters: extubation success, mechanical ventilation duration, time spent in ICU, reintubation rate, and mortality rate. Two-hour trial failed in 31 patients in T-tube and 32 patients in PSV group, of whom 17 and 23, respectively, were successfully extubated (P<0.001, chi(2)test). Mechanical ventilation lasted significantly longer in T-tube than in PSV group (187 hours vs 163 hours, respectively, P<0.001, Mann-Whitney test). Also, patients in T-tube group spent significantly more time in ICU than patients in PVS group (241 hours [interquartile range 211-268] vs 210 hours [211-268], respectively, P<0.001, Mann-Whitney test). Reintubation was required in 8 and 6 patients in T-tube and PVS group, respectively, and death occurred in 4 and 2 patients, respectively, during ICU stay. Patients with COPD who failed the 2-hour spontaneous breathing trial had more favorable outcome when PVS rather than T-tube method was used for weaning from mechanical ventilation.


Hydrodynamic measurement of double-layer repulsion between colloidal particle and flat plate.
Electrostatic repulsion acting across an electrolyte solution lends stability to paints and printing inks and influences cell adhesion, aggregation, and fusion. A new technique is used to measure this interaction when one of the bodies has colloidal dimensions. The potential energy profile of interactions between a 15-micrometer polystyrene sphere and a glass plate is determined by observing the distribution of separation distances (0.2 to 0.4 micrometer) that the particle samples by Brownian motion. Measurements of the speed with which the sphere is carried by linear shear flow along the wall are used to calculate separation distance. Although evidence for hydrodynamic lift is found, it is not included in the potential profile.


The length of guide RNA and target DNA heteroduplex effects on CRISPR/Cas9 mediated genome editing efficiency in porcine cells.
The clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a versatile genome editing tool with high efficiency. A guide sequence of 20 nucleotides (nt) is commonly used in application of CRISPR/Cas9; however, the relationship between the length of the guide sequence and the efficiency of CRISPR/Cas9 in porcine cells is still not clear. To illustrate this issue, guide RNAs of different lengths targeting the EGFP gene were designed. Specifically, guide RNAs of 17 nt or longer were sufficient to direct the Cas9 protein to cleave target DNA sequences, while 15 nt or shorter guide RNAs had loss-of-function. Full-length guide RNAs complemented with mismatches also showed loss-of-function. When the shortened guide RNA and target DNA heteroduplex (gRNA:DNA heteroduplex) was blocked by mismatch, the CRISPR/Cas9 would be interfered with. These results suggested the length of the gRNA:DNA heteroduplex was a key factor for maintaining high efficiency of the CRISPR/Cas9 system rather than weak bonding between shortened guide RNA and Cas9 in porcine cells.


Kinesiophobia, Knee Self-Efficacy, and Fear Avoidance Beliefs in People with ACL Injury: A Systematic Review and Meta-Analysis.
To improve the understanding of the psychological impacts of anterior cruciate ligament (ACL) injury, a systematic review synthesizing the evidence on knee self-efficacy, fear avoidance beliefs and kinesiophobia following ACL injury is needed. The aim of this systematic review was to investigate knee self-efficacy, fear avoidance beliefs and kinesiophobia following ACL injury, and compare these outcomes following management with rehabilitation alone, early and delayed ACL reconstruction (ACLR). Seven databases were searched from inception to April 14, 2022. Articles were included if they assessed Tampa Scale of Kinesiophobia (TSK), Knee Self-Efficacy Scale (KSES), or Fear Avoidance Beliefs Questionnaire (FABQ). Risk of bias (RoB) was assessed using domain-based RoB tools (ROBINS-1, RoB 2, RoBANS), and GRADE-assessed certainty of evidence. Random-effects meta-analyses pooled outcomes, stratified by time post-injury (pre-operative, 3-6 months, 7-12 months, > 1-2 years, > 2-5 years, > 5 years). Seventy-three studies (70% high RoB) were included (study outcomes: TSK: 55; KSES: 22; FABQ: 5). Meta-analysis demonstrated worse kinesiophobia and self-efficacy pre-operatively (pooled mean [95% CI], TSK-11: 23.8 [22.2-25.3]; KSES: 5.0 [4.4-5.5]) compared with 3-6 months following ACLR (TSK-11: 19.6 [18.7-20.6]; KSES: 19.6 [18.6-20.6]). Meta-analysis suggests similar kinesiophobia > 3-6 months following early ACLR (19.8 [4.9]) versus delayed ACLR (17.2 [5.0]). Only one study assessed outcomes comparing ACLR with rehabilitation only. Knee self-efficacy and kinesiophobia improved from pre-ACLR to 3-6 months following ACLR, with similar outcomes after 6 months. Since the overall evidence was weak, there is a need for high-quality observational and intervention studies focusing on psychological outcomes following ACL injury.


Post-transcriptional regulation of urokinase mRNA. Identification of a novel urokinase mRNA-binding protein in human lung epithelial cells in vitro.
We sought to determine if urokinase expression is regulated at the post-transcriptional level in cultured lung epithelial cells. We also sought to determine if differences in urokinase expression by cultured human lung carcinoma and non-malignant lung epithelial subtypes were attributable to post-transcriptional regulatory mechanisms. Urokinase was expressed by phenotypically diverse lung carcinoma cell lines as well as non-malignant small airway epithelial cells and bronchial epithelial cells. Using gel mobility shift and UV cross-linking assays, we identified a 30-kDa urokinase mRNA-binding protein that selectively bound to a 66-nucleotide protein-binding fragment of urokinase mRNA. The urokinase mRNA-binding protein is found in the cytosolic but not nuclear extracts of non-malignant lung epithelial cells; whereas, it is found in the nuclear but not cytosolic extracts of selected malignant carcinoma-derived cells that express relatively large amounts of urokinase. Chimeric beta-globin/urokinase cDNA containing the urokinase mRNA-binding protein binding sequence destabilized otherwise stable beta-globin mRNA. Our results demonstrate that urokinase gene expression in lung epithelial and lung carcinoma-derived cells is regulated at the post-transcriptional level. The mechanism involves an interaction between a 66-nucleotide sequence of the urokinase mRNA 3'-untranslated region with a newly recognized urokinase mRNA-binding protein to regulate urokinase mRNA stability.


Rapidly progressing extracanal invasive resorption.
Frank and Bakland coined the term "Extracanal invasive resorption" (EIR) to identify a resorptive entity that has been variously classified. This external resorption originates in the cementum adjacent to the periodontal ligament. The lesion is believed to be a response to injury and irritation of the periodontal ligament, or to pressure from ectopic eruption, orthodontic pressure, intracoronal bleaching, periodontal treatment, or an unknown idiopathic cause.


Conservation of Tropical Forests in the Anthropocene.
If current trends continue, the tropical forests of the Anthropocene will be much smaller, simpler, steeper and emptier than they are today. They will be more diminished in size and heavily fragmented (especially in lowland wet forests), have reduced structural and species complexity, be increasingly restricted to steeper, less accessible areas, and be missing many heavily hunted species. These changes, in turn, will greatly reduce the quality and quantity of ecosystem services that tropical forests can provide. Driving these changes will be continued clearance for farming and monoculture forest plantations, unsustainable selective logging, overhunting, and, increasingly, climate change. Concerted action by local and indigenous communities, environmental groups, governments, and corporations can reverse these trends and, if successful, provide future generations with a tropical forest estate that includes a network of primary forest reserves robustly defended from threats, recovering logged and secondary forests, and resilient community forests managed for the needs of local people. Realizing this better future for tropical forests and people will require formalisation of land tenure for local and indigenous communities, better-enforced environmental laws, the widescale roll-out of payments for ecosystem service schemes, and sustainable intensification of under-yielding farmland, as well as global-scale societal changes, including reduced consumerism, meat consumption, fossil fuel reliance, and population growth. But the time to act is now, while the opportunity remains to protect a semblance of intact, hyperdiverse tropical forests.


On the collapse of bacterial endotoxin resistance following hemorrhage.
Unanesthetized immature albino rabbits exposed to 2 hours of severe but reversible hemorrhagic shock induced with aseptic precautions by multiple cardiac bleedings exhibited no increase in susceptibility to single intravenous injections of 200 microg./kg. E. coli endotoxin administered 4 hours post retransfusion, a quantity of endotoxin that was found to be the largest dose uniformly non-lethal to normal rabbits. Paired and randomly selected rabbits treated identically except for the additional procedure of a femoral arterial cutdown and ligation (without aseptic precautions) exhibited increases in susceptibility to the same endotoxin of several hundredfold. This effect could not be attributed to the femoral cutdown and arterial ligation alone since such trauma when coupled with sham cardiac bleedings failed to increase susceptibility to 200 microg./kg. of endotoxin. These data appear valid since sham cardiac bleedings produced no detectable impairment of myocardial contractility, while 2 hours of hemorrhagic shock at 50 mm. Hg with the Lamson reservoir technique caused an increase in endotoxin susceptibility comparable to that seen when cardiac bleedings were combined with a non-sterile femoral arterial cutdown and ligation. The mechanisms increasing the susceptibility to E. coli endotoxin were investigated. It was found that (a) rabbit femoral skeletal muscle is normally contaminated with clostridia, (b) the use of aseptic femoral wounding precautions exerted some suggestive protective influence, (c) the use of aseptic wounding precautions combined with immediate topical sulfanilamide and wound closure exerted a significant protective influence, and (d) prophylactic polyvalent gas gangrene antitoxin protected in a manner not demonstrable when diphtheria antitoxin was employed as a control. These observations suggest that clostridial wound infection is one mechanism whereby a femoral arterial cutdown lowers endotoxin resistance of the rabbit following hemorrhagic shock. It is, however, not the only mechanism since the ligation of a femoral artery during hemorrhagic shock led to edema following retransfusion equivalent to a mean of approximately 30 per cent of the original circulating plasma volume. The intensification of shock caused by this transudation presumably intensified reticulo-endothelial injury, and thus further lowered the resistance of the rabbit to an intravenous injection of endotoxin 4 hours following retransfusion.


A Unique Signature of Cardiac-Induced Cranial Forces During Acute Large Vessel Stroke and Development of a Predictive Model.
Cranial accelerometry is used to detect cerebral vasospasm and concussion. We explored this technique in a cohort of code stroke patients to see whether a signature could be identified to aid in the diagnosis of large vessel occlusion (LVO) stroke. A military-grade three-axis accelerometer was affixed to a headset. Accelerometer and electrocardiogram (ECG) outputs were digitized at 1.6 kHz. We call the resulting digitized signals the "headpulse." Three-minute recordings were performed immediately after computed tomography (CT) angiography (CTA) and/or immediately before and after attempted mechanical thrombectomy in patents with suspected stroke. The resulting waveforms were inspected by eye and then subjected to supervised machine learning (MATLAB Classification Learner R2018a) to train a model using fivefold cross-validation. Of 42 code stroke subjects with recordings, 19 (45%) had LVO and 23 (55%) had normal CTAs. In patients without LVO, ECG-triggered waveforms followed a self-similar time course revealing that the headpulse is highly coupled to the cardiac contraction. However, in most patients with LVO, headpulses showed little cardiac contraction correlation. We term this abnormality "chaos" and parameterized it with 156 measures of trace-by-trace variation from the ECG-signal-averaged mean for machine learning model training. Selecting the best model, using biometric data only, we properly classified 15/19 LVOs and 20/23 non-LVO patients, with receiver operating characteristic curve area = 0.79, sensitivity of 73%, and specificity of 87%, P < 0.0001. Headpulse waveforms following thrombectomy showed return of cardiac contraction correlation. Headpulse recordings performed on patients with suspected acute stroke significantly identify those with LVO. The lack of temporal correlation of the headpulse with cardiac contraction and resolution to normal may reflect changes in cerebral blood flow and may provide a useful technique to triage stroke patients for thrombectomy using a noninvasive device.


Analysis of the growth of recombination-deficient strains of Escherichia coli K-12.
Cultures of recombination-deficient strains of Escherichia coli are composed of three classes of cells: (i) viable cells, which can undergo 20 or more generations, (ii) residually dividing cells, which can undergo fewer than 20 generations (probably an average of fewer than 6), and (iii) nondividing cells, which are incapable of a single division. The nonviable but residually dividing cells contribute to the mass increase of the culture, but not to the viability, thus accounting for the apparent dissimilarity in the effects of rec mutations on growth rates and viabilities. We have determined the frequencies of cells in each of the three classes, and, by making a simplifying assumption concerning the relative division times of viable and residually dividing cells, we have been able to describe mathematically the growth of the rec(-) cultures.


Acute Swine Model for Assessing Biocompatibility of Biomedical Interface Materials.
We established an acute animal model for early, straightforward, and reproducible assessment of a biocompatible material interface. Bilateral femoral artery-to-vein shunts were created in 12 pigs: two tubes per shunt, the left two coated and the right two uncoated. We evaluated two groups: uncontrolled flow (UF; shunt flow unregulated) and controlled flow (CF; shunt flow ∼50 mL/min). For each case on each side, two shunts were evaluated: one for 1 h and the other for 3 h. Arterial blood gas and complete blood count were recorded at baseline, 1, and 3 h. Mean shunt flows were 532 ± 88 mL/min UF and 52 ± 8 mL/min CF. Differences in flow were much smaller in CF (0.5 mL/min; 1% of mean flow) than UF (24.8 mL/min; 5% of mean flow). In UF, significant changes occurred: in pH, from start of shunting through 1 h; in pO2 and pCO2, from start through 3 h. This swine model using bilateral femoral shunts with controlled blood flow provides a reliable, reproducible, easily implemented method by which to evaluate biocompatibility of device coatings at an early stage of investigation.


A new type of specific interneuron in the monkey hippocampus forming synapses exclusively with the axon initial segments of pyramidal cells.
By means of Golgi staining and gold-toning, we have found an interneuron in the pyramidal cell layer of the hippocampus which forms synapses exclusively on the axon initial segments of pyramidal neurons. An individual initial segment receives up to 30 symmetrical synapses from one axo-axonic cell. Each axo-axonic cell is in synaptic contact with the axon initial segments of several hundred pyramidal neurons. The interneuron is thus ideally situated to synchronize the output of a large population of pyramidal cells and so might be involved in the generation of rhythmic activity and in epileptogenesis.


IPV Characteristics, Childhood Violence, and Adversities as Risk Factors for Being Victimized in Multiple IPV Relationships.
Empirical knowledge regarding risk factors for intimate partner violence (IPV) from multiple partners (MP) is scarce and sought by clinicians and many women themselves for the prevention of future intimate partner violence relationships (IPVRs). Quantitative data were obtained through a structured interview with a stratified sample of help-seeking women (N = 154) with no (n = 48, 0IPVR), one (n = 55, 1IPVR), or multiple (n = 51, 2IPVR) IPVRs. This study investigated the association between (a) childhood family violence, (b) other childhood adversities, (c) victimization and perpetration of IPV in the last (index) relationship, and (d) controlling sociodemographic and contextual variables, and the following dependent variables: (a) women with 1IPVR and 2IPVR compared with 0IPVR and (b) women with 1IPVR compared with 2IPVR. Multivariate logistic regression analyses indicated that, compared with nonvictimized women, IPV victimized women were nearly three times more likely to report childhood sexual abuse. They also reported a higher frequency of peer victimization and a higher likelihood of having an immigrant partner. In addition, the length of the index relationship was shorter for IPV victimized women. Compared with women with 1IPVR, women with IPV by MP were more likely to report childhood emotional abuse and less education, and they were less likely to be immigrants. The two groups of IPV victimized women were indistinguishable regarding characteristics of victimization and perpetration of IPV. This study indicated that there were other risk factors for IPV by MP than for IPV in general and highlighted the importance of addressing parenting and emotional care in IPV families.


Constitutive activation of SHP2 in mice cooperates with ICSBP deficiency to accelerate progression to acute myeloid leukemia.
Myeloproliferative disorders (MPDs) are characterized by cytokine hypersensitivity and apoptosis resistance. Development of a block in myeloid differentiation is associated with progression of MPD to acute myeloid leukemia (AML) and portends poor prognosis. Identifying molecular markers of this transition may suggest targets for therapeutic intervention. Interferon consensus sequence binding protein (ICSBP, also known as IRF8) is an interferon-regulatory transcription factor that functions as a leukemia tumor suppressor. In mice, ICSBP deficiency induces an MPD that progresses to AML over time, suggesting that ICSBP deficiency is sufficient for myeloproliferation, but additional genetic lesions are necessary for AML. Since activity of ICSBP is influenced by tyrosine phosphorylation state, we hypothesized that mutations in molecular pathways that regulate this process might synergize with ICSBP deficiency for progression to AML. Consistent with this, we found that constitutive activation of SHP2 protein tyrosine phosphatase synergized with ICSBP haploinsufficiency to facilitate cytokine-induced myeloproliferation, apoptosis resistance, and rapid progression to AML in a murine bone marrow transplantation model. Constitutive SHP2 activation cooperated with ICSBP deficiency to increase the number of progenitors in the bone marrow and myeloid blasts in circulation, indicating a block in differentiation. Since SHP2 activation and ICSBP deficiency may coexist in human myeloid malignancies, our studies have identified a molecular mechanism potentially involved in disease progression in such diseases.


Characterization of the insulinotropic potency of polyunsaturated fatty acids.
In this study we have assessed the individual abilities of the essential fatty acids, linoleic and linolenic acids, to release insulin and compared their insulinotropic potencies with those of the more established nutrient insulin secretagogues, glucose and arginine. In each experiment, a total of six islets microdissected from three mice were preperifused at the rate of 1 ml/min with Krebs-Ringer bicarbonate buffer, pH 7.4, containing 2% bovine albumin and 5.5 mM glucose (basal) with a continuous supply of 95% O2-5% CO2 at 37 C for 1 h. After collecting basal samples, the effects of 27.7 mM glucose, 20 mM arginine, 10 mM linoleic acid (18:2, omega 6), and 5 mM linolenic acid (18:3, omega 3) were tested using a sandwich protocol that entails 20-min alternating periods of stimulation with a secretagogue and a washout with basal perifusion. These nutrient concentrations were selected from initial experiments performed to characterize their dose-response effects on insulin secretion. Effluent samples were collected throughout each experiment for measurement of insulin by RIA. In one series of experiments, islets were challenged three times with 27.7 mM glucose, 10 mM linoleic acid, and 5 mM linolenic acid. In another set of experiments, islets were perifused with 20 mM arginine, 27.7 mM glucose, and 10 mM linoleic acid. All of these nutrients stimulated insulin release in a dose-dependent manner. In comparing the insulinotropic potencies of these secretagogues, we assessed insulin secretion as the integrated areas under the curve during 20 min of perifusion with a given nutrient. Thus, the mean integrated area under the curve per 20 min above basal in the presence of 27.7 mM glucose was 6,516 +/- 1,435 pg, which was not significantly different from the value of 4,772 +/- 866 pg obtained during arginine perifusion. However, the area under the curve during 20 min above basal obtained in the presence of linoleate and linolenic acid (8,712 +/- 1,949 and 10,506 +/- 1,490 pg, respectively) were significantly different (P less than 0.05) from those calculated during arginine and glucose perifusions. There was no statistically significant difference between the effects of these two fatty acids at the concentrations tested. In conclusion, our data suggest that linoleic acid and linolenic acid may be, at least in this murine islet preparation, as effective in stimulating insulin release as glucose and arginine, hitherto used to assess the abilities of nutrients to stimulate insulin secretion. However, it remains to be seen whether the efficacy of these polyunsaturated fatty acids in insulin release by murine islets will be obtained in experiments performed on human islets.


Analysis of the humoral immune response to Chlamydia outer membrane protein 2.
The humoral immune response to Chlamydia outer membrane protein 2 (Omp2) was studied. Omp2 is a highly genus-conserved structural protein of all Chlamydia species, containing a variable N-terminal fragment. To analyze where the immunogenic parts were localized, seven highly purified truncated fusion proteins constituting different regions of the protein were produced (Chlamydia pneumoniae-Omp2aa23-aa93, Chlamydia psittaci-Omp2aa23-aa94, and Chlamydia trachomatis-Omp2aa23-aa84, aa87-aa547, aa23-aa182, aa167-aa434, aa420-aa547). By an enzyme-linked immunosorbent assay with serologically defined patient sera, Omp2 was found to be a major immunogen of both C. pneumoniae and C. trachomatis infections (P < 0.0001). The humoral immune responses were not confined to any particular region of the Omp2 protein, and no species-specific anti-Omp2 immunoglobulins were detected.


Threonine catabolism in Trypanosoma brucei.
L-Threonine is catabolized by Trypanosoma brucei to give equimolar quantities of glycine and acetate. The pathway, which involves the two enzymes L-threonine dehydrogenase (EC 188.8.131.52) and aminoacetone synthase (acetyl-CoA:glycine C-acetyltransferase, EC 18.104.22.168) and subsequent hydrolysis of the acetyl-CoA, is most active in cultured trypanosomes but is also present in bloodstream forms. L-Threonine dehydrogenase from both culture and bloodstream forms of trypanosomes has an apparent molecular weight of between 28 000 and 38 000, and is sensitive to a wide range of sulphydryl reagents.


Tumor-specific idiotype vaccines. II. Analysis of the tumor-related network response induced by the tumor and by internal image antigens (Ab2 beta).
In this study the tumor-specific immuneresponse induced by irradiated tumor cells (L1210/GZL) and by anti-idiotype antibodies was analyzed. The anti-idiotype antibodies (Ab2) were made against the paratope of a monoclonal antitumor antibody (11C1) that recognizes a tumor-associated antigen which cross-reacts with the mouse mammary tumor virus-encoded envelope glycoprotein 52. Two Ab2, 2F10 and 3A4, induced idiotypes expressed by the monoclonal antitumor antibodies 11C1 and 2B2. Cytotoxic T cells, generated by immunization with irradiated tumor cells, lyse 2F10 and 3A4 hybridoma cells. Furthermore, immunization with Ab2 induces tumor-specific cytotoxic T lymphocytes. The frequency of tumor-reactive cytotoxic T lymphocyte was found to be similar in mice immunized with Ab2 or irradiated tumor cells when examined at the precursor level. However, only 2F10 induces protective immunity against the growth of L1210/GZL tumor cells. The depletion of a L3T4+ T cell population from 2F10 immune mice was found to increase the effectiveness of transferred T cells to induce inhibition of tumor growth. The inability of 3A4 to induce antitumor immunity could be correlated with the presence of a population of Lyt2+ regulatory T cells. Collectively, these results demonstrate the existence of a regulatory network controlling the expression of effective tumor immunity. Our results demonstrate that selection of binding site-related Ab2 may not be a sufficient criteria for the development of an idiotype vaccine. A better understanding of the regulatory interactions induced by anti-idiotypes is needed for the design of effective antitumor immunotherapy.


Evaluation of the transfection efficacies of quaternary ammonium salts prepared from sophorolipids.
Five quaternary ammonium amphiphilic compounds were synthesized from sophorolipid 1. These compounds were formulated in aqueous media and some of them (5 and 6) produced well-defined supramolecular aggregates which were characterized by DLS and zeta measurements. Their capacity to transfect four different eukaryotic cell lines in vitro was assessed. To evaluate the influence of the carbohydrate head group from the sophorolipids on the transfection efficacies, their deglycosylated analogues were also synthesized and tested for gene delivery. For all the compounds, the use of DOPE as a helper lipid in a 1 : 1 molar ratio with the ammonium-based lipids was required to obtain homogeneous formulations. The transfection results indicate that quaternary ammonium-based sophorolipids proved to be more efficient pDNA carriers than their deglycosylated counterparts. Moreover, the presence of the carbohydrate head group clearly contributed to the good biocompatibility of these cationic lipids. These cationic sophorolipid derivatives thus offer good potential for the development of new vectors for gene delivery based on renewable resources.


[Thyrotoxic periodic paralysis--an unusual complication of hyperthyroidism].
Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism. We describe two patients with TPP. A 26-year-old man from Vietnam had weight loss, tachycardia, palpitations and heat intolerance for five months. Episodic leg and arm weakness developed three months after debut of symptoms. The second patient, a 23-year old woman from the Philippines, had had episodic leg weakness in the evenings after dinner for three weeks. Her attacks resolved spontaneously overnight. Physical examination of both patients revealed tachycardia and symmetrical proximal weakness involving both arms and legs. ECG and electrolyte analysis indicated a severe hypokalaemia; thyroid function tests showed hyperthyroidism. Both patients were diagnosed as having Graves' thyrotoxicosis and TPP. They were initially treated with propranolol and subsequently with carbimazole. The first patient had recurrence of thyrotoxicosis and paralysis after 16 months, whereas the second patient has remained symptom-free. TPP is most common in Asian males, very few cases are reported in females. In Western countries TPP is rare, but with increasing immigration, TPP is likely to occur more frequently.


[Machado de Assis and psychiatry: a chapter in the relations between art and clinical practice in Brazil].
Madness, its place in society, and the tenuous boundaries separating it from reason became a constant concern in Machado deAssis' literary production as of 1880, when a shift can be observed in his work. Clinical studies exploring the relations between art and madness have mentioned this writer countless times. The article offers an overview of Brazilian psychiatry's perception of the arts, artists, and the creative process in the early decades of the twentieth century. It presents three studies on Machado de Assis and his works, written during that period by psychiatrists who interpreted artistic phenomenon from the perspective of psychopathology, and endeavors to identify the inner logic of these approaches.


Exploring a frequency-domain attention-guided cascade U-Net: Towards spatially tunable segmentation of vasculature.
Developing fully automatic and highly accurate medical image segmentation methods is critically important for vascular disease diagnosis and treatment planning. Although advances in convolutional neural networks (CNNs) have spawned an array of automatic segmentation models converging to saturated high performance, none have explored whether CNNs can achieve (spatially) tunable segmentation. As a result, we propose multiple attention modules from a frequency-domain perspective to construct a unified CNN architecture for segmenting vasculature with desired (spatial) scales. The proposed CNN architecture is named frequency-domain attention-guided cascaded U-Net (FACU-Net). Specifically, FACU-Net contains two innovative components: (1) a frequency-domain-based channel attention module that adaptively tunes channel-wise feature responses and (2) a frequency-domain-based spatial attention module that enables the deep network to concentrate on foreground regions of interest (ROIs) effectively. Furthermore, we devised a novel frequency-domain-based content attention module to enhance or weaken the high (spatial) frequency information, allowing us to strengthen or eliminate vessels of interest. Extensive experiments using clinical data from patients with intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA) demonstrated that the proposed FACU-Net met its design goal. In addition, we further investigated the association between varying (spatial) frequency components and the desirable vessel size/scale attributes. In summary, our preliminary findings are encouraging, and further developments may lead to deployable image segmentation models that are spatially tunable for clinical applications.


Augmentation of venous return by adrenergic agonists during spinal anesthesia.
To test the effectiveness of adrenergic agonists in correcting the vascular sequelae of spinal anesthesia, we used venous reservoir volume (RV) and mean arterial pressure (MAP) as indices of the changes in venous capacitance and arterial resistance produced by adrenergic agonists in dogs anesthetized with pentobarbital and undergoing cardiopulmonary bypass (CPB). A CPB-based technique was chosen both to prevent drug and reflex effects on the heart from influencing the results and to provide a convenient means by which to monitor venous capacitance. Total spinal anesthesia significantly decreased both RV and MAP relative to steady-state CPB values. Return of these hemodynamic alterations to baseline was attempted using pure alpha- and beta-adrenergic agonists, and a mixed adrenergic agonist (phenylephrine, isoproterenol, and ephedrine, respectively). Isoproterenol increased RV, but further decreased MAP. Phenylephrine increased MAP but not RV. Ephedrine increased both MAP and RV. We conclude that a mixed adrenergic agonist such as ephedrine more ideally corrects the noncardiac circulatory sequelae of spinal anesthesia than does either a pure alpha- or beta-adrenergic agonist.


Consensus dynamics on temporal hypergraphs.
We investigate consensus dynamics on temporal hypergraphs that encode network systems with time-dependent, multiway interactions. We compare these consensus processes with dynamics evolving on projections that remove the temporal and/or the multiway interactions of the higher-order network representation. For linear average consensus dynamics, we find that the convergence of a randomly switching time-varying system with multiway interactions is slower than the convergence of the corresponding system with pairwise interactions, which in turn exhibits a slower convergence rate than a consensus dynamics on the corresponding static network. We then consider a nonlinear consensus dynamics model in the temporal setting. Here we find that in addition to an effect on the convergence speed, the final consensus value of the temporal system can differ strongly from the consensus on the aggregated, static hypergraph. In particular, we observe a first-mover advantage in the consensus formation process: If there is a local majority opinion in the hyperedges that are active early on, then the majority in these first-mover groups has a higher influence on the final consensus value-a behavior that is not observable in this form in projections of the temporal hypergraph.


Operative Treatment and Clinical Outcomes in Peripheral Vascular Trauma: The Combined Experience of Two Centers in the Endovascular Era.
Arterial traumas of the extremities are quite rare in civilian records; nevertheless, patients with trauma of limbs are admitted daily in emergency departments worldwide. The up-to-date information about epidemiology and treatment (open vs. endovascular surgery) comes from war records and it is not always easy getting data on mortality and morbidity in these patients. The aim of this study is to analyze the approach (open or endovascular) and the outcome of patients with vascular trauma of upper limbs (from the subclavian artery) and/or lower limbs (distal to the inguinal ligament), in the greater Milan area. A retrospective analysis was conducted on data recorded by the emergency departments of two hospitals of the greater Milan between 2009 and 2017. We collected all patients with arterial injuries of the limbs in terms of demography, injury patterns, clinical status at admission, therapy (open or endovascular approach), and outcomes in terms of limb salvage and survival. We studied 52 patients with vascular trauma of extremities. The main mechanism of trauma was road accident (48.1%), followed by criminal acts (32.7%), self-endangering behavior (13.5%), work (3.8%), and sport accidents (1.9%). Associated lesions (orthopedic, neurological, and/or venous lesions of the limbs) were present in 39 patients (75%). All patients underwent emergency surgery, forty-six patients (88.5%) by open repair (polytetrafluoroethylene or greater saphenous vein bypass grafts, arterial suture or ligation), whereas endovascular approach was used only in 6 patients (11.5%), all treated with embolization. The overall postoperative mortality rate was 5.7% (3 patients). Among survivors, we report 5 major amputations of the lower limbs, 3 of them after bypass graft infection, and 2 after graft failure. The rate of limb salvage was 90.4%. Isolated arterial trauma of the extremities are rare, usually they occur in the setting of multiple trauma patients. Despite progresses in surgical techniques, there are still controversies in diagnosis and treatment of these patients. We treated most cases with open surgery (n = 46), choosing endovascular approach (embolization performed mainly by interventional radiologists) in difficult anatomic districts. We believe that, during decision-making of the surgical strategy, it is important to consider the anatomical site of lesions and the general condition of the patients. Moreover, in case of multiple trauma, we suggest a multidisciplinary approach to provide the best medical care to the victims.


A modified intramedullary nail interlocking design yields improved stability for fatigue cycling in a canine femur fracture model.
Intramedullary nailing has evolved to become the standard of care for most diaphyseal femoral and tibial fractures, as well as an expanding number of metaphyseal fractures. Owing to the unstable nature of some fractures, the intramedullary device may be subjected to significant stresses owing to a lack of solid cortical contact after nailing. In such cases, excessive interfragmentary motion (due to construct toggle) has been shown to occur. Such motion increases the likelihood of a non- or delayed-union. In the current study, two versions of a modified, angle stable interlocking design were subjected to fatigue testing in a segmental defect fracture model representing a canine femur. As a control, a third group of constructs were stabilized with a traditional nail that allowed a small amount of toggle. All constructs were subjected to 50,000 fatigue cycles representing 12 weeks of cage activity at physiologic levels of combined axial-torsional loading. Torsional testing pre- and post-fatigue revealed 4.6 +/- 1.3 degrees of toggle in the traditional nail and no toggle with the angle stable nail designs. The stable nails were also significantly stiffer in axial compression and torsion before and after cycling. These data indicate that the enhanced stability of the modified interlocking designs can be maintained throughout fatigue cycling in a challenging fracture model.


Effects of papaverine, chloracyzine, and bencyclane on local blood flow and oxygen tension in cat brain.
In experiments on 100 cats with multichannel recording, the effects of three vasodilators - papaverine, chloracyzine, and bencyclane (Halidor) - on the volume velocity of the blood flow (by microthermistor technique) and on oxygen tension (by polarography) in the carotid artery, the cerebral cortex, the thalamus, and in white matter were tested. Considerable differences were found in the effects of the drugs mentioned, although all of them augment the total and local blood flow in the brain, and in most instances elevate the oxygen tension in arterial blood and cerebral tissue. Characteristic of papaverine is a uniform augmentation of blood supply to the cerebral cortex, the thalamus, and white matter, whereas chloracyzine, and especially bencyclane, primarily augment the blood supply to the cerebral cortex. In an analogous way the drugs tested influence the cerebral blood flow and oxygen tension in experimental cerebral ischaemia induced by intracarotid infusion of a serotonin solution.


[Nutrition and cancer (author's transl)].
There is evidence of the epidemiological role of nutrition in the pathogenesis of various forms of human diseases; several components of nutrition are known to have a carcinogenic effect in man. In terms of epidemiology, however, alcoholism is most important which through the development of malnutrition enhances the risk of carcinosis of the upper gastrointestinal tract particularly in smokers. Nutritional deficiences have an influence on the incidence of cancer of the stomach, cervix and thyroid. Overnutrition favours the development of certain forms of cancer such as malignant diseases of the colon, pancreas, kidney, mamma, ovary, endometrium and prostate.


Neoplasms arising in congenital giant nevi: morphologic study of seven cases and a review of the literature.
Congenital giant nevi are complex cutaneous malformations composed of melanocytic and occasionally neural supportive elements. Malignant neoplasms arising in this setting are not uncommon, and their histologic appearances often differ significantly from the typical pattern of malignant melanoma. We report six patients with neoplasms arising in congenital giant nevi and one patient with a neoplasm arising in an extensive congenital blue nevus, and present a description of the neoplastic patterns encountered. These patterns include 1) poorly differentiated small round cell cancer, 2) malignant cellular blue nevus, 3) spindle-cell malignant tumor with lamellar cell (pseudomeissnerian) differentiation, 4) so-called minimal deviation melanoma, 5) heterologous malignant mesenchymal differentiation including rhabdomyosarcoma and liposarcoma, and 6) undifferentiated spindle cell cancer. We have reviewed the literature in order to address the question of frequency of malignant transformation in congenital giant nevi, the reported experience with the morphology of these cancers, and the histogenesis of these sometimes complex neoplasms as it is illuminated by our current understanding of the embryology of the neural crest.


Nutritional enrichment of broiler breast meat through dietary supplementation of Indian ginseng Withania somnifera and synbiotic substances under semi-arid climatic conditions.
The present study was conducted to explore the effect of supplementation of Withania somnifera and synbiotics alone or in combination on the composition of broiler breast meat under heat stress conditions. A 42-day feeding trial was conducted on 360 broiler chicks randomly allotted into eight treatment groups with three replicates each under completely randomized design. The T1 group was kept as control whereas T2-T4 were supplemented with 0.5%, 1%, and 1.5% W. somnifera root powder; T5 and T6 were supplemented with 0.025% and 0.050% synbiotic and T7 and T8 were fed on diet containing 0.25% W. somnifera+0.025% synbiotic and 0.50% W. somnifera+0.05% synbiotic, respectively. Three broilers from each replicate were sacrificed at the end of the trial to estimate crude protein (CP), ether extract and ash content of the breast muscle on dry matter basis. Significantly higher CP values and lower ether extract values were observed in 1.5% W. somnifera supplemented group (T4) or in group supplemented with 0.50% W. somnifera and 0.05% synbiotic (T8). The ash content of breast meat was observed non-significant in T1-T4 groups however the inclusion of synbiotics in T5-T8 groups significantly raised the ash contents. The study concluded that inclusion of 0.5% W. somnifera with 0.05% synbiotic substance enriches the total protein content and reduces the total lipids content of broiler breast meat under heat stress conditions.


Establishing Clinical Cut-points on the Pediatric PROMIS-Pain Interference Scale in Youth With Abdominal Pain.
Abdominal pain is a common presenting complaint in youth seeking medical care and can be debilitating. Therefore, it is important to understand the impact of pain on functioning using a clinically sensitive approach. The National Institutes of Health has established a common core of psychometrically precise measures through the Patient-Reported Outcomes Measurement Information System (PROMIS) initiative. The Pediatric PROMIS-Pain Interference (PPPI) scale was developed to measure pain-related interference, drawing from existing legacy measures. However, its clinical validity has not been thoroughly established in clinical populations. The current study sought to develop clinical cut-points and investigate the validity of the PPPI in a large sample (N=5281) of youth presenting to gastroenterological care with abdominal pain symptoms. Convergent validity of the PPPI was investigated. Quartile and tertile groupings of the PPPI were calculated and compared with cut-points derived from healthy populations and mixed convenience samples on clinical outcomes via multivariate analyses of variance. There was good evidence of convergent validity. The tertile solution was superior in classifying different levels of pain-related outcomes as compared with other cut-points. The tertile solution suggested the following PPPI groupings: minimal (≤51), moderate (52 to 59), and severe (≥60). Results suggest the PPPI is a valid measure with clinically meaningful cut-points to assess pain-related interference in youth with abdominal pain.


The Effect of Mechanical Frequency on Piezoelectrochemical Energy Harvesters.
Microenergy harvesters such as piezoelectro-chemical (PEC) devices allow the extraction of low-frequency mechanical energy, which might otherwise be lost. Recent literature on PEC harvesters has noted that the input mechanical frequency affects the device current outputs, but this effect is not well understood. Mechanical energy sources often have variable frequencies, so understanding PEC harvester performance as a function of frequency is vital for the optimization of these devices. Using a commercially available lithium ion pouch cell as a test system, this work finds that applying a square-wave frequency with the fastest strain rate and longest hold time maximizes PEC current output. There is a monotonic increase in peak power, maximum half-cycle energy, and energy conversion efficiency as the input mechanical frequency approaches zero. This indicates that PEC harvesters have more flexibility in operating frequency than piezoelectric harvesters, as PEC harvesters do not have resonance or antiresonance frequencies.


Prevalence of obesity and metabolic syndrome in Korean adults.
We studied the prevalence and trend of obesity and metabolic syndrome in Korean adults aged at least 20 years using Korean National Health Examination and Nutrition Survey data from 1998 and 2001. The prevalence of body mass index (BMI) > or = 25 kg m(-2) among Korean adults in 2001 was 32.9% in men and 27.4% in women, and the number of Korean men with BMI > or = 25 kg m(-2) has increased markedly since 1998. A significant positive association between obesity and socioeconomic status was found in Korean men, whereas a significant negative association was identified in Korean women. The prevalence rates of waist circumference (WC) > or = 90 cm in men and WC > or = 85 cm in women were 23.4% and 23.1% in 2001 respectively. The prevalence of metabolic syndrome among Korean adults was 15-30% according to various criteria of metabolic syndrome. Future studies are needed to determine the changes in prevalence of obesity and contributing factors for obesity in Koreans.


Get healthy from an early age to gain years (and quality) of life!
As it is well known, in the 2000s the average lifespan reached unhoped-for values compared to those of the early 20th century. This incredible achievement was the combined result of improved living conditions and constant medical advancements, which together have contributed to a significant reduction in mortality. The sharp decline in infant mortality led to a general aging of the population and consequently to the great challenge of keeping the elderly healthy and self-sufficient for as long as possible. In Italy, 30% of the over-65s are not affected by any major condition and 20% have a chronic disease with no particular effects on their physical and cognitive functions, while 50% have multiple chronic morbidities that - in at least 40% of cases -result in consequent mobility problems or difficulties in performing everyday activities. The Italian data presented here do not differ much from those of other industrialised countries in Europe and North America. Studies show that every one out of two elderly people is at risk for "frailty", which is regression to a weak, childlike state, exhibiting behaviours such as communication difficulties, lack of self-sufficiency, crying, incontinence, frequent falls. An important aspect of becoming a healthier elderly person is the attention to the care and feeding of children. In fact, it has been hypothesised that poor nutrition of the fetus and infant could be the cause of permanent changes in specific organs and tissues. For example, in a clinical trial, the altered development of pancreas due to inadequate early feeding resulted in increased susceptibility to type 2 diabetes and related metabolic complications, with health impacts for the patient and economic consequences for the community at large. In conclusion, these two ages, normally viewed as opposites, prove to be similar enough to the point where a strong connection can be made between paediatrics and geriatrics. The above lays the groundwork for addressing issues related to the aging process through the consideration of an individual's life as a whole, abandoning the previous method of dividing life into stages with the aim of developing increasingly personalised and biologically-driven health care.


Tolerability and Efficacy of Memantine as Add on Therapy in Patients with Migraine.
Prophylactic migraine treatment has always been a challenge. Efficacy and tolerability are two main issues in current approved migraine prevention regimens. Since some migraine patients fail approved preventative agents, experts are always seeking newer agents. Memantine, a glutaminergic antagonist, could potentially be one of these agents. Objective of current study is assessing the efficacy of memantine as a preventative migraine treatment and its potential side effects. In this study, 127 migraine patients meeting the criteria for starting preventative therapy (> 4 headache days/month) are included in the study. All patients were previously failed in at least one trial of adequate preventive therapy. After a 30 day baseline observation, patients started memantine for 3 months, beginning at 5 mg/day, which increased by 5 mg/week up to a maximum of 20 mg a day if symptoms did not improve. Headache frequency, duration, and severity were assessed at the end of the treatment phase. 102 patients completed the study. In the study population, headache frequency reduced from 9.9 days/month at baseline to 5 days/month at 3 months (P < .001). The mean severe pain reduced from 6.9 to 3.6 at 3 months (P < .001). Headache duration significantly reduced at 3 months, compared with baseline (P < .001). Side effects related to memantine consumption were uncommon and generally mild. Based on preliminary data, there is some evidence that memantine might be useful in the treatment of refractory migraine. This is in line with previous pilot and open label studies. However, double blind studies are still needed.


Incident Reporting in Perfusion: Current Perceptions on PIRS-2.
The Australia and New Zealand College of Perfusionists' (ANZCP) Perfusion Incident Reporting System was established in 1998 and has evolved to an open access on-line incident perfusion reporting system (PIRS-2). Changes were made to PIRS-2 to promote learning from what went well in unexpected situations. A 9-question survey was e-mailed to the PIRS-2 contact group to elicit feedback on attitudes to voluntarily reporting perfusion-related incidents and near-miss events to PIRS-2. In August 2019, a 9-question survey using SurveyMonkey® (San Mateo Ca) was e-mailed to 198 perfusionists currently on the ANZCP PIRS-2 e-mail contacts group. Responses for all responding practicing perfusionists were totaled and expressed as a percentage of the total number of respondents. The respondents were then grouped by region and responses were expressed as a percentage of respondents from each region as well as for grouped responses from Australia/New Zealand (ANZ) and non-ANZ respondents. The response rate was 49.5% with 95 practicing perfusionists completing the survey. In the 12 months before the survey, 22% of respondents had submitted reports to PIRS-2, whereas 79% had read e-mailed reports. Unit culture was the most frequently cited barrier to reporting from all respondents (19%; 0% to 40% by region). Twenty-five percentage of Australian respondents cited unit culture as a barrier to reporting vs. 0% of New Zealand respondents. A combination of concern of discovery and identification of region ranked second as a barrier for 17% of all respondents. The open access ANZCP PIRS-2 voluntary incident reporting in perfusion was widely viewed as relevant and beneficial to both individual practice and to team performance. A high likelihood to considering reporting incidents is tempered by the well-established barriers of ease of the reporting system, the fix and forget phenomenon, concerns of discovery, and a defensive unit culture.


MiR-4282 inhibits proliferation, invasion and metastasis of human breast cancer by targeting Myc.
To investigate the expression and role of MicroRNA 4282 (miR-4282) in the development of breast cancer. In situ hybridization was performed to investigate the expression of miR-4282 in human breast cancer tissues. Cell lines stably over-expressed miR-4282 were established by lentivirus transfection. The effects of miR-4282 on the biological behavior of breast cancer cells were then explored in vitro. The results showed that miR-4282 was down-regulated in human breast cancer tissues and was particularly in invasive and metastatic tumors. In addition, the expression of miR-4282 was related to the occurrence of metastasis and the clinical grade of breast cancer. Recovery of miR-4282 expression in the cell could inhibit the proliferation of breast cancer cells, blocked G1-S phase and promoted breast cancer cell apoptosis, inhibited breast cancer cell migration and invasion. Besides, miR-4282 also significantly enhanced the sensitivity of breast cancer cells to paclitaxel. The results of bioinformatics analysis combined with qRT-PCR and Western blot demonstrated that Myc might be the target gene of miR-4282 in breast cancer. miR-4282 inhibited the occurrence and development of breast cancer by regulating Myc, which made it a new target for clinical diagnosis and treatment of breast cancer.


Visual Outcomes in Leber Hereditary Optic Neuropathy Patients With the m.11778G>A (MTND4) Mitochondrial DNA Mutation.
Leber hereditary optic neuropathy (LHON) is a maternally inherited bilaterally blinding optic neuropathy, predominantly affecting otherwise healthy young individuals, mostly men. The visual prognosis is generally poor, with most patients worsening to at least 20/200 visual acuity. The m.11778G>A (MTND4) mitochondrial DNA mutation is the most common cause of LHON and is associated with poor outcomes and limited potential for meaningful visual recovery. Treatments for LHON are limited, and clinical trials are hampered by inadequate data regarding the natural history of visual loss and recovery. In this article, we review the current literature specifically related to visual function of LHON patients with the m.11778G>A mutation. Literature review was performed using MEDLINE through PubMed, Cochrane Reviews Library, and Orpha.net with search terms of "Leber hereditary optic neuropathy," "LHON," "ND4," "G11778A," "visual acuity," "nadir," "natural history," and "registry." All English-language, peer-reviewed publications with study cohorts of at least 5 LHON patients with the molecularly confirmed m.11778G>A mutation were included. Meta-analysis of 12 retrospective and 3 prospective studies provided visual function information on 695 LHON patients with the m.11778G>A mutation, 100 (14.4%) of whom were reported to have "recovered" some vision, although definitions of "recovery" varied among studies and idebenone use could not always be excluded. When incorporating age at onset of visual loss into the analyses, and specifically addressing those patients aged 15 years or older, meaningful visual recovery occurred in 23 of 204 (11.3%) patients. A younger age at onset, especially less than 12 years, portends a better visual prognosis and a different natural history of visual loss progression and recovery than in adults. The classic presentation of LHON patients with the m.11778G>A mutation of severe visual loss with rare or poor recovery from nadir still holds true for most affected individuals. Among patients 15 years and older, recovery of meaningful vision likely occurs in less than 20% of patients, irrespective of how recovery is defined, and ultimate visual acuities of better than 20/200 are rare. Adequate prospective studies with sufficient sample sizes of genotypically homogeneous untreated LHON patients stratified by age, immediately enrolled when symptomatic, followed regularly for adequate periods of time with consistent measures of visual function, and analyzed with a standard definition of visual improvement are unfortunately lacking. Future clinical trials for LHON will require more standardized reporting of the natural history of this disorder.


Incidence and risk factors of retinopathy of prematurity in a tertiary eye hospital in Tehran.
To determine the incidence and risk factors of retinopathy of prematurity (ROP) in premature infants referred to a tertiary eye hospital during 2003-7 to provide preliminary evidence about ROP in Iran. In a cross-sectional study, data for premature infants screened for ROP in Farabi Eye Hospital including possible risk factors and eye exams' results were recorded and analysed using chi(2), univariate and multiple regressions. Severe ROP was defined as ROP needing treatment or stage 4 or 5 of ROP. Among 953 premature infants, there were 329 (34.5%) different stages of ROP. Severe ROP was seen in 22.6% (215/953) of infants (16.5%: treatable, 6.1%: advanced untreatable). The mean gestational age (GA) and birth weight (BW) of infants with severe ROP were 28.8 (SD 2.4) weeks and 1256 (389) g respectively. Univariate analysis showed a significant relation between GA, BW, oxygen therapy, blood transfusion and ROP (p<0.001), while multiple-regression methods showed GA, BW and oxygen therapy as independent predictors of ROP (p<0.001, 0.019 and 0.033, respectively). The authors observed a relatively high incidence of ROP in this series, especially its severe form affecting relatively more mature infants, which merits further investigation. GA, BW and oxygen therapy were independent ROP determinants.


Quantum Quench in PT-Symmetric Luttinger Liquid.
A Luttinger liquid (LL) describes low energy excitations of many interacting one dimensional systems, and exhibits universal response both in and out of equilibrium. We analyze its behavior in the non-Hermitian realm after quantum quenching to a PT-symmetric LL by focusing on the fermionic single particle density matrix. For short times, we demonstrate the emergence of unique phenomena, characteristic to non-Hermitian systems, that correlations propagate faster than the conventional maximal speed, known as the Lieb-Robinson bound. These emergent supersonic modes travel with velocities that are multiples of the conventional light cone velocity. This behavior is argued to be generic for correlators in non-Hermitian systems. In the long time limit, we find typical LL behavior, extending the LL universality to the nonequilibrium, non-Hermitian case. Our analytical results are benchmarked numerically and indicate that the dispersal of quantum information is much faster in non-Hermitian systems.


Technique to control pH in vicinity of biodegrading PLA-PGA implants.
This in vitro study was performed to examine if the pH decrease in the vicinity of degrading polylactic acid (PLA) and polyglycolic acid (PGA) polymers can be offset by incorporation of basic salts within PLA-PGA implants. It has been suggested that such pH lowering results in adverse effects, which may be responsible for biocompatibility concerns raised recently about PLA and PGA polymers. The results indicated that all three salts investigated in this study were successful in controlling the decrease in pH due to the acidic degradation products of the copolymer. The pH of the test media for the control group fell to a value of 3.0 at 9 weeks. Implants containing calcium carbonate maintained the pH value between 7.4 and 6.3 throughout the degradation process. Implants with calcium hydroxyapatite and sodium bicarbonate controlled the pH values between 6.9 and 4.3 and 8.2 and 4.5, respectively. At 3 weeks, marked swelling of implants containing calcium carbonate or sodium bicarbonate was observed relative to the control implants. The molecular weight and mass changes in the implants did not show any significant differences at 9 weeks. Thus, results from this in vitro model show that a significant decrease in pH in the vicinity of PLA-PGA implants can be avoided by incorporating basic salts.


A Leu262Pro mutation in the integrin beta(3) subunit results in an alpha(IIb)-beta(3) complex that binds fibrin but not fibrinogen.
Platelet retraction of a fibrin clot is mediated by the platelet fibrinogen receptor, alpha(IIb)beta(3). In certain forms of the inherited platelet disorder, Glanzmann thrombasthenia (GT), mutant alpha(IIb)beta(3) may interact normally with fibrin yet fail to support fibrinogen-dependent aggregation. We describe a patient (LD) with such a form of GT. Platelets from LD supported normal clot retraction but failed to bind fibrinogen. Platelet analysis using flow cytometry and immunoblotting showed reduced but clearly detectable alpha(IIb)beta(3), findings consistent with type II GT. Genotyping of LD revealed 2 novel beta(3) mutations: a deletion of nucleotides 867 to 868, resulting in a premature stop codon at amino acid residue 267, and a T883C missense mutation, resulting in a leucine (Leu) 262-to-proline (Pro) substitution. Leu262 is highly conserved among beta integrin subunits and lies within an intrachain loop implicated in subunit association. Leu262Probeta(3) cotransfected with wild-type alpha(IIb) into COS-7 cells showed delayed intracellular maturation and reduced surface expression of easily dissociable complexes. In human embryonic kidney 293 cells, Leu262Probeta(3) formed a complex with endogenous a(v) and retracted fibrin clots similarly to wild-type beta(3). The same cells, however, were unable to bind immobilized fibrinogen. The molecular requirements for alpha(IIb)beta(3) to interact with fibrin compared with fibrinogen, therefore, appear to differ. The region surrounding beta(3) Leu262 may maintain beta(3) in a fibrinogen-binding, competent form, but it appears not to be required for receptor interactions with fibrin.


Full Percutaneous Transforaminal Lumbar Interbody Fusion Using the Facet-sparing, Trans-Kambin Approach.
This was a prospective, multicenter, consecutive case series' study. The objective of this study was to evaluate a novel facet-sparing, percutaneous transforaminal lumbar interbody fusion (pTLIF) technique consisting of percutaneous insertion of an expandable interbody cage through an endoscopic cannula with the trans-Kambin approach and complemented with percutaneous transpedicular screws and rods. Lumbar interbody fusion by open or minimally invasive surgery is the usual treatment for degenerative disk disease but requires a relatively long recovery period. The transforaminal trans-Kambin approach is a standard in endoscopic spine surgery for safe intradiscal access without facet resection. Preoperative and postoperative Visual Analogue Scale (VAS) and Oswestry Disability Index scores were quantitatively assessed at 1, 3, 6, and 12 months after surgery and then every 12 months for patients treated with pTLIF between 2009 and 2018 in 2 health care centers. An immediate postoperative control computed tomography scan was performed, whereas conventional postoperative x-ray controls were performed at 1 month and 1 year. Statistical evaluation was performed with the Student t test. A total of 51 patients (mean age, 59.3 y) were evaluated. The overall mean VAS score for axial lumbar pain improved from 6.6 to 1.8 (P<0.01), mean VAS score for leg pain from 5.5 to 1.2 (P<0.01), and mean Oswestry Disability Index scores from 30.3 to 11.8 (P<0.01) postoperatively with a mean follow-up of 27.9 months (range, 1-77.8 mo). Median estimated blood loss was 103.6 mL. Postoperative complications included 12 (22%) cases with transitory ipsilateral dysesthesia, 2 (4%) cases with transitory ipsilateral muscle weakness, and 3 (6%) clinically asymptomatic cases with radiologic cage subsidence. Median hospital stay was 1.4 days (range, 1-3.2 d). Postoperative scores for pTLIF significantly improved with minimal blood loss and no long-term complications. On the basis of this experience, the facet-sparing pTLIF is a reliable and safe technique with early hospital discharge, opening the way to outpatient instrumented spine surgery. Level III.


The earliest cotton fibers and Pan-regional contacts in the Near East.
Fiber technology (cordage and textile) has played a central role in all human societies for thousands of years, and its production, application and exchange have deep roots in prehistory. However, fiber remains have only rarely been observed in prehistoric sites because they tend to decay quickly in normal environmental conditions. To overcome preservation problems of macroscopic remains, we employed microbotanical analysis on soils from anthropogenic sediments in activity areas at Tel Tsaf in the Jordan Valley, Israel (ca. 5,200-4,700 cal BC), and recovered fiber microremains. This includes at least two types of bast fibers and the earliest evidence of cotton in the Near East, some of which were dyed in various colors. Some of these fibers likely represent the remnants of ancient clothing, fabric containers, cordage, or other belongings. The cotton remains, probably derived from wild species originating in South Asia, predate the oldest known cotton domestication in the Indus Valley by about two millennia. Tel Tsaf played a pivotal role in trans-regional trade and exchange networks in the southern Levant, and the presence of cotton at the site points to possible connections with the Indus Valley as early as 7,200 years ago.


Diagnosis and treatment of malignant pleural mesothelioma.
There are three major challenges in the diagnosis of malignant pleural mesothelioma: mesothelioma must be distinguished from benign mesothelial hyperplasia; malignant mesothelioma (and its subtypes) must be distinguished from metastatic carcinoma; and invasion of structures adjacent to the pleura must be demonstrated. The basis for clarifying the first two aspects is determination of a panel of monoclonal antibodies with appropriate immunohistochemical evaluation performed by highly qualified experts. Clarification of the third aspect requires sufficiently abundant, deep biopsy material, for which thoracoscopy is the technique of choice. Video-assisted needle biopsy with real-time imaging can be of great assistance when there is diffuse nodal thickening and scant or absent effusion. Given the difficulties of reaching an early diagnosis, cure is not generally achieved with radical surgery (pleuropneumonectomy), so liberation of the tumor mass with pleurectomy/decortication combined with chemo- or radiation therapy (multimodal treatment) has been gaining followers in recent years. In cases in which surgery is not feasible, chemotherapy (a combination of pemetrexed and platinum-derived compounds, in most cases) with pleurodesis or a tunneled pleural drainage catheter, if control of pleural effusion is required, can be considered. Radiation therapy is reserved for treatment of pain associated with infiltration of the chest wall or any other neighboring structure. In any case, comprehensive support treatment for pain control in specialist units is essential: this acquires particular significance in this type of malignancy.


Effect of social support on fetal movement self-monitoring behavior in Chinese women: a moderated mediation model of health beliefs.
Strengthening the management of women's self-monitoring during pregnancy is important to reduce fetal death in utero and improve maternal and infant outcomes. However, due to the lack of awareness among pregnant women about the importance of self-monitoring fetal movement, resulting in low behavioral compliance, adverse pregnancy outcomes remain common in China. This study aimed to investigate the relationship between social support and health beliefs and the self-monitoring behavior of fetal movement. In addition, we examined the moderating and mediating effects of health beliefs on fetal movement self-monitoring. This cross-sectional study was conducted on 200 postpartum mothers in a tertiary hospital in China. The mothers were asked to complete a socio-demographic questionnaire, the fetal movement self-monitoring behavior questionnaire, the fetal movement self-monitoring health beliefs questionnaire, and the social support rating scale. Data from the questionnaires were analyzed and compared using SPSS 24.0 and PROCESS 3.2. The results of this study showed that the total scores of social supports, health beliefs, fetal movement self-monitoring were 42.98 ± 11.65, 78.605 ± 13.73, and 11.635 ± 2.86, respectively. The study found that when social support and health beliefs were included in the regression equation, both social support and health beliefs showed a positive correlation with fetal movement self-monitoring. Health beliefs partially mediated the effect of social support on fetal movement self-monitoring, accounting for 37.5% of the total effect. Social support and health beliefs play a crucial role in influencing the self-monitoring behavior of fetal movements. Therefore, strengthening social support and health beliefs during pregnancy has the potential to improve compliance with fetal movement self-monitoring behaviors for pregnant women.


An Ab initio study of the ligand field and charge-transfer transitions of Cr(CN)(6)(3-) and Mo(CN)(6)(3-).
High-level ab initio calculations on the excited states of Cr(CN)63- and Mo(CN)63- are reported. For the latter complex, a rather large 10 Dq value of 42 000 cm-1 is obtained, reflecting the increased covalency. The lowest lying charge-transfer transitions for both complexes are predicted to be of the type ligand-to-metal, an assignment in agreement with the photochemical behavior of Cr(CN)63-. A good correspondence between the well-known experimental spectrum of the chromium complex and the theoretical CASPT2 excitation energies is found.


A Hybrid in Situ Approach for Cost Efficient Image Database Generation.
The visualization of results while the simulation is running is increasingly common in extreme scale computing environments. We present a novel approach for in situ generation of image databases to achieve cost savings on supercomputers. Our approach, a hybrid between traditional inline and in transit techniques, dynamically distributes visualization tasks between simulation nodes and visualization nodes, using probing as a basis to estimate rendering cost. Our hybrid design differs from previous works in that it creates opportunities to minimize idle time from four fundamental types of inefficiency: variability, limited scalability, overhead, and rightsizing. We demonstrate our results by comparing our method against both inline and in transit methods for a variety of configurations, including two simulation codes and a scaling study that goes above 19 K cores. Our findings show that our approach is superior in many configurations. As in situ visualization becomes increasingly ubiquitous, we believe our technique could lead to significant amounts of reclaimed cycles on supercomputers.


Staphylococcal plasmids that replicate and express erythromycin resistance in both Streptococcus pneumoniae and Escherichia coli.
Plasmid pSA5700 from Staphylococcus aureus coding for erythromycin (EmR) and chloramphenicol (CmR) resistance was transformed into Streptococcus pneumoniae. High-copy-number and EmR constitutive mutants of this plasmid were isolated. Transformation frequencies in S. pneumoniae as high as 70% were obtained with a constitutive plasmid as donor DNA, into a recipient cell containing a resident, inducible, high-copy-number plasmid. With the aid of these high frequencies, the site of constitutive mutations could be mapped via a simple marker rescue technique that uses purified restriction endonuclease-generated fragments. One of the EmR constitutive mutants, pFB9, a plasmid originating from a Gram-positive host, was shown to replicate and express EmR and CmR in a Gram-negative organism, Escherichia coli. Four derivatives of pFB9 containing large (0.6-0.9 megadalton) insertion sequences that arose spontaneously in E. coli demonstrated unusual transforming activity, as well as enhanced EmR, in E. coli. The inserted elements mapped to the region in front of the EmR gene. Three of these inserted elements had the size and restriction patterns of insertion sequence IS1, IS2, and IS5. Plasmid pFB9 and derivatives are useful for isolation of new insertion sequences and for comparison of gene expression and illegitimate recombination between Gram-positive and Gram-negative species.


The effect of ferrule presence and type of dowel on fracture resistance of endodontically treated teeth restored with metal-ceramic crowns.
The purpose of the present study was to comparatively evaluate the effect of presence of a 2 mm ferrule and different type of dowels on fracture resistance of mandibular premolars. Fifty uniradicular mandibular premolars were divided into five groups (n = 10). Ten teeth received no treatment (group I). Samples in group II & III were decoronated 2 mm above cemento-enamel junction and received custom cast dowel-core and fiber dowel-composite core respectively, with 2 mm ferrule. Samples in group IV & V were decoronated at CEJ and were restored using cast dowels and fiber dowel-composite cores, without any ferrule. The restored teeth received metal ceramic crowns and were mechanically loaded. The specimens were subjected to a static load, until fracture, to determine the fracture resistance and fracture mode. The samples with 2 mm ferrule had a higher fracture resistance than non ferrule groups. Within non ferrule groups, there were no significant differences in the fracture resistance. Specimen restored with cast dowel had more incidence of non-repairable fracture. Presence of ferrule increased the fracture resistance of endodontically treated teeth. In case of absence of ferrule, fiber dowels had similar fracture resistance as that of cast dowels and showed increased incidence of repairable fracture.


Invasion of insect cells by Spiroplasma citri involves spiralin relocalization and lectin/glycoconjugate-type interactions.
Spiroplamas are helical, cell wall-less bacteria belonging to the Class Mollicutes, a group of microorganisms phylogenetically related to low G+C, Gram-positive bacteria. Spiroplasma species are all found associated with arthropods and a few, including Spiroplasma citri are pathogenic to plant. Thus S. citri has the ability to colonize cells of two very distinct hosts, the plant and the insect vector. While spiroplasmal factors involved in transmission by the leafhopper Circulifer haematoceps have been identified, their specific contribution to invasion of insect cells is poorly understood. In this study we provide evidence that the lipoprotein spiralin plays a major role in the very early step of cell invasion. Confocal laser scanning immunomicroscopy revealed a relocalization of spiralin at the contact zone of adhering spiroplasmas. The implication of a role for spiralin in adhesion to insect cells was further supported by adhesion assays showing that a spiralin-less mutant was impaired in adhesion and that recombinant spiralin triggered adhesion of latex beads. We also showed that cytochalasin D induced changes in the surface-exposed glycoconjugates, as inferred from the lectin binding patterns, and specifically improved adhesion of S. citri wild-type but not of the spiralin-less mutant. These results indicate that cytochalasin D exposes insect cell receptors of spiralin that are masked in untreated cells. In addition, competitive adhesion assays with lectins strongly suggest spiralin to exhibit glycoconjugate binding properties similar to that of the Vicia villosa agglutinin (VVA) lectin.


[Precocious puberty, Gh deficiency and obesity can affect final height in patients with myelomeningocele: comparison of males and females].
Patients with myelomeningocele show an increased incidence of endocrinological disorders during their childhood. These disorders can ulteriorly affect the adult height of these patients who are already extremely short. In the present study we determined the final height in 21 patients (11 females aged 20.55 +/- 3.54 years; 10 males aged 20.99 +/- 2.94 years) with myelomeningocele. The endocrinological implications were investigated by clinical and laboratory assessment at control and an accurate retrospective evaluation of individual clinical history. Auxological data indicated that in male patients mean final height was significantly less (P < 0.05) than target height, but in females the difference between final height and target height was even more marked (P < 0.001). Comparison of SDS for adult height between males (-2.04 +/- 1.89) and females (-4.36 +/- 2.24) evidenced a statistically significant difference (P < 0.05). The analysis of endocrinological data showed that 7 females had had precocious puberty not treated; no case of precocious puberty was evidenced in males. In 4 females we observed plasmatic IGF-1 and IGFBP-3 concentrations significantly reduced either for chronological age and pubertal stage; this finding emerged in only 1 male. Plasmatic thyroid hormone and adrenal steroid concentrations resulted normal in both groups. Finally, obesity, considered as BMI > 90%, resulted present since childhood in 4 females and 2 males. Our data show that females with myelomeningocele have a statistically greater decrease of their adult stature respect to males. This difference is probably due to a more significant incidence in females of endocrinological diseases. Thus, we believe that a better statural prognosis may be joined in these patients (particularly in girls), through a careful endocrinological follow-up, performed from their births, in order to ensure a prompt identification and treatment of the cases of precocious puberty, impaired GH secretion or obesity.


Management of a patient with locally advanced prostate cancer with degarelix: a case report.
Gonadotropin releasing hormone (GnRH) antagonists, such as degarelix, are emerging as an androgen deprivation therapy primary agents in a treatment of advanced prostate cancer. The role of GnRH antagonists in management of lower urinary tract symptoms associated with prostate cancer has not been clearly established. In this report, we describe the case of a patient with locally advanced prostate cancer who presented with symptoms of urinary retention and renal failure. The use of degarelix in this patient led to a rapid reduction in the prostate-specific antigen level; however, obstructive symptoms persisted despite the use of degarelix and radiation treatment.


Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection.
More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.


Physicians' role in environmental issues.
Our health and the health of our patients are linked closely to the quality of our environment. As physicians, we ourselves must learn and then we must educate our patients about the importance of preventing health-endangering pollution of our air, water, food, and soil. As busy physicians, we need access to the most current, important new scientific information regarding environmental degradation where our patients work and live so we can appreciate the clinical problems that some patients present to us today. The National Association of Physicians for the Environment (NAPE) is an organization of physicians and 46 medical professional societies serving to promote protection of the environment as a fundamental responsibility of physicians and other health professionals. NAPE sponsors national conferences, promotes the publication of current "best practices" information in various general and specialty areas, and serves as a national forum for the discussion of issues and dissemination of scientifically valid information needed for physician and patient education.


SERS-based direct and sandwich assay methods for mir-21 detection.
In this study, two different assay methods were developed using a surface enhanced Raman scattering (SERS) label for sensitive miR-21 detection. In the first method (direct assay), the miR-21 probe was attached to SERS-labelled, rod-shaped gold nanoparticles and hybridised with the target miR-21, which was previously immobilised onto the gold slide. In the second method (sandwich assay), the target miR-21 was captured by an miR-21 probe immobilised onto the gold slide and hybridised with a second miR-21 probe immobilised on the SERS-labeled, rod-shaped gold nanoparticles. SERS signals of developed assays were obtained via a SERS spectrum of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) on the rod-shaped nanoparticles. The calibration curves were plotted to measure the different concentrations of miR-21. The detection limits of the direct and sandwich assays, which last less than 40 min, were found to be 0.36 and 0.85 nM, respectively. The developed SERS-based methods offer rapid, selective, sensitive and easy detection of miR-21, especially compared to conventional PCR-based methods.


[Dental status and related factors in an occupational health service in Northern France].
Few data are available concerning the dental health of adults in France. This study was designed to describe dental status, oral health behaviour and factors associated with caries among workers followed by an occupational health service in Northern France. A representative sample of workers was selected between May and July 2006. Data were collected by occupational health physicians using a questionnaire completed during a face-to-face interview and a dental examination. After descriptive analysis of the variables, two groups were defined according to the degree of caries as assessed by the Significant Caries Index. Factors associated with the degree of caries were investigated using logistic regression adjusted to age. 420 workers with a mean age of 34.6(±10.4) years were included. The mean DMFT (Decayed Missing Filled Teeth) score and the mean number of decayed teeth were 8.9 (± 6.5) and 1.3 (±2.8), respectively. Three independent factors associated with high caries rates were identified: level of education less than Baccalaureate (ORa = 1.85; p < 0.05), regular consumption of sweet snacks and/or sweet drinks (ORa = 2.01; p < 0.05) and a last dental visit motivated by pain or a reason other than preventive care (ORa = 1.89; p < 0.05). This study showed a high need for care and oral health education in this population of workers. More oral health education programmes should be set up in the adult working population by occupational health services.


Assessment of cervical length and the relationship between short cervix and preterm birth.
Premature effacement of the cervix, or short cervix, in the midtrimester of pregnancy currently represents the strongest predictor of spontaneous preterm birth. Numerous studies have examined the relationship between short cervix and preterm birth, and although differences in sensitivity and predictive value exist, the overwhelming consensus indicates that the risk of preterm birth increases with decreasing cervical length. Cutoff values for cervical length range from less than 25 mm to less than 15 mm depending on patient characteristics and gestational age. Importantly, short cervix is more sensitive for predicting earlier forms of prematurity (at <32 weeks) than later forms of prematurity (>32 weeks). Cervical length measured at 18 to 24 weeks' gestation appears to be the most valuable measurement. Cervical length assessments can be performed by digital examination, a cervical measurement device, transabdominal ultrasound, or transvaginal ultrasound. Transvaginal ultrasound is the most reliable method to evaluate cervical length, but it is not available in all locations. Current clinical practice standards do not recommend universal screening for cervical length; however, results of randomized controlled clinical trials provide evidence to support expanded screening programs by individual practitioners.


From p- to n-Type Mixed Conduction in Isoindigo-Based Polymers through Molecular Design.
Organic mixed ionic and electronic conductors are of significant interest for bioelectronic applications. Here, three different isoindigoid building blocks are used to obtain polymeric mixed conductors with vastly different structural and electronic properties which can be further fine-tuned through the choice of comonomer unit. This work shows how careful design of the isoindigoid scaffold can afford highly planar polymer structures with high degrees of electronic delocalization, while subtle structural modifications can control the dominant charge carrier (hole or electron) when probed in organic electrochemical transistors. A combination of experimental and computational techniques is employed to probe electrochemical, structural, and mixed ionic and electronic properties of the polymer series which in turn allows the derivation of important structure-property relations for this promising class of materials in the context of organic bioelectronics. Ultimately, these findings are used to outline robust molecular-design strategies for isoindigo-based mixed conductors that can support efficient p-type, n-type, and ambipolar transistor operation in an aqueous environment.