The future of subalpine forests in the Southern Rocky Mountains: Trajectories for Pinus aristata genetic lineages.
Like many other high elevation alpine tree species, Rocky Mountain bristlecone pine (Pinus aristata Engelm.) may be particularly vulnerable to climate change. To evaluate its potential vulnerability to shifts in climate, we defined the suitable climate space for each of four genetic lineages of bristlecone pine and for other subalpine tree species in close proximity to bristlecone pine forests. Measuring changes in the suitable climate space for lineage groups is an important step beyond models that assume species are genetically homogenous. The suitable climate space for bristlecone pine in the year 2090 is projected to decline by 74% and the proportional distribution of suitable climate space for genetic lineages shifts toward those associated with warmer and wetter conditions. The 2090 climate space for bristlecone pine exhibits a bimodal distribution along an elevation gradient, presumably due to the persistence of the climate space in the Southern Rocky Mountains and exclusion at mid-elevations by conditions that favor the climate space of other species. These shifts have implications for changes in fire regimes, vulnerability to pest and pathogens, and altered carbon dynamics across the southern Rockies, which may reduce the likelihood of bristlecone pine trees achieving exceptional longevity in the future. The persistence and expansion of climate space for southern bristlecone pine genetic lineage groups in 2090 suggests that these sources may be the least vulnerable in the future. While these lineages may be more likely to persist and therefore present opportunities for proactive management (e.g., assisted migration) to maintain subalpine forest ecosystem services in a warmer world, our findings also imply heighted conservation concern for vulnerable northern lineages facing range contractions.


[Carotid endarterectomy for atherosclerotic carotid artery stenosis].
Several randomized controlled trials (RCTs) have demonstrated carotid endarterectomy (CEA) to be more beneficial for the prevention of recurrent or first-ever ischemic stroke than treatment with antiplatelet agents in patients with moderate-severe stenosis of the cervical internal carotid artery. CEA is the standard treatment for such lesions; however, other RCTs have demonstrated carotid artery stenting (CAS) with a protective device to be comparable to CEA in patients with or without radiological or medical high-risks for CEA, although the selection criteria among these treatments have not yet been established in clinical practice. This review compares the results of RCTs valuating the superiority of CEA over medical treatment or CAS, preoperative examination, procedures of CEA, perioperative management and complications, long-term results, and indications for CEA based on the currently available evidence-based publications. A preoperative evaluation of the patients'medical condition, including atherosclerosis, is therefore important to minimize the perioperative complications of CEA, because myocardial infarction during the perioperative period is frequently observed in patients undergoing CEA. A through radiological examination such as plaque imaging is essential for selecting appropriate treatment strategies involving revascularization or medical treatment for atherosclerotic carotid artery stenosis. In addition, the surgical indications, particularly for asymptomatic lesions, should be carefully considered in light of the recent improvements in medical treatments including antihypertensive agents and statins.


[Successful treatment of a persistent rhino-cerebral mucormycosis in a pediatric patient with a debut of acute lymphoblastic leukemia].
The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.


Teenage alcohol use in the Australian twin register: genetic and social determinants of starting to drink.
Retrospective information about teenage alcohol use was obtained from 1589 adult twin pairs aged 20-30 years from the Australian twin register. Twin pairs were highly concordant both for teenage drinking (or abstinence) and for early versus late onset of drinking. Sociodemographic variables (e.g., paternal occupation and parental religious affiliation) and psychosocial variables (e.g., personality and attitudinal traits), assessed when the twins were adults, were comparatively poor predictors of teenage drinking. Environmental influences on onset of drinking appeared to be sex-specific, i.e., uncorrelated over twins from unlike-sex pairs. Among drinkers, early versus late onset of drinking was more strongly influenced by inherited factors in females, but by shared features of the social environment (e.g., family background or school experience) in males.


Influence of the definition of "metabolically healthy obesity" on the progression of coronary artery calcification.
Debates whether metabolically healthy obesity (MHO) increases the cardiovascular risk might be due to the metabolic instability of MHO or the absence of a perfect definition of MHO. Therefore, we aimed to investigate the influence of the MHO phenotype on the coronary artery calcium score (CACS) progression according to definition of MHO. We analyzed a retrospective cohort with a CACS of 0 at baseline and available serial CACS measurements taken ≥ 12 months apart (n = 1,218). Obesity was defined as BMI ≥ 25 kg/m2, and MHO was defined as obesity accompanied by ≤ 1 (MHO class I) or 0 (MHO class II) components of metabolic syndrome (MetS). During a median follow-up of 45 months, 32.2% of MHO class I and 10.2% of MHO class II subjects developed MetS. Compared to non-obese/metabolically healthy subjects (reference group), hazard ratios (HR) for development of MetS were 2.174 (95% confidence interval [CI]: 1.513-3.124) and 1.166 (95% CI: 0.434-3.129) for MHO class I and II subjects, respectively. The MHO class I subjects showed a significantly increased risk of CACS progression as compared to the reference group (HR: 1.653; 95% CI: 1.144-2.390), whereas MHO class II subjects did not (HR: 1.195; 95% CI: 0.514-2.778). Among subjects with MHO class I, no significant CACS progression was observed in the subjects who maintained metabolic health during follow-up (HR: 1.448; 95% CI: 0.921-2.278). The risks of metabolic deterioration and CACS progression were significant in subjects with MHO class I, but not in those with MHO class II.


Endovascular edge-to-edge mitral valve repair: short-term results in a porcine model.
The edge-to-edge technique is an accepted method for the surgical repair of a regurgitant mitral valve. This study reports the initial use of an endovascular technology that enables a double-orifice edge-to-edge mitral valve repair without cardiopulmonary bypass in an animal model. Adult pigs (n=14) were anesthetized, and left thoracotomy was performed for epicardial echo imaging. Using femoral vein access, a steerable guide catheter was placed transseptally into the left atrium. An implantable clip designed to grasp and approximate the middle scallops of the anterior and posterior mitral leaflets was introduced through the guide catheter. The clip was opened in the left atrium, advanced through the mitral orifice, and retracted to grasp the leaflet edges. When a functional double-orifice valve was confirmed by echo, the clip was closed to coapt the leaflets and detached from the delivery catheter. Before final clip detachment, echo demonstrated a double orifice in all 14 animals. In 2 studies, the clip released from the anterior mitral leaflet. Retrospective analysis of echo images indicated an incomplete grasp of the anterior leaflet. Immediate postmortem examination revealed that the clip successfully approximated the middle scallops of the anterior and posterior leaflets in all 12 double-orifice studies. This study demonstrates for the first time that an endovascular system can be successfully used to perform the edge-to-edge repair technique in a nondiseased porcine model. This technique is potentially applicable as a percutaneous catheterization laboratory procedure for the treatment of mitral regurgitation in humans.


Autophagosome formation during varicella-zoster virus infection following endoplasmic reticulum stress and the unfolded protein response.
Autophagy is a recently recognized component of the life cycle of varicella-zoster virus (VZV). We have documented abundant autophagosome formation in skin vesicles (final site of virion assembly) from randomly selected cases of varicella and zoster. The fact that autophagy was an early event in the VZV replication cycle was documented by finding infected vesicle cells with the VZV IE62 protein confined to the nucleus. Next, we pursued studies in VZV-infected cultured cells to define whether autophagy was preceded by endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). First, we demonstrated that autophagosome formation in infected cells closely resembled that seen after treatment of cells with tunicamycin, a potent initiator of ER stress. Second, we demonstrated a marked expansion of ER size in both VZV-infected cells and cells transfected with the predominant VZV glycoprotein complex gE/gI. An enlarged ER is critical evidence of ER stress, which in turn is relieved by the UPR. To this end, we documented the UPR by detecting the alternatively spliced form of the XBP1 protein as well as CHOP (C/EBP homologous protein), both transcriptional activators of other UPR genes in an ER stress-dependent manner. Because VZV does not encode inhibitors of autophagy, the above results suggested that autophagy was a common event in VZV-infected cells and that it was provoked at least in part by ER stress secondary to overly abundant VZV glycoprotein biosynthesis, which led to UPR activation in an attempt to maintain cellular homeostasis.


Participants' experiences of being debriefed to placebo allocation in a clinical trial.
Participants in placebo-controlled clinical trials give informed consent to be randomized to verum or placebo. However, researchers rarely tell participants which treatment they actually received. We interviewed 4 participants in a trial of acupuncture for irritable bowel syndrome before, during, and after they received a course of placebo treatments over 6 weeks. During the final interview, we informed participants that they had received a course of placebo treatments. We used an idiographic phenomenological approach based on the Sheffield School to describe each participant's experiences of being blinded to and then debriefed to placebo allocation. The participants' experiences of blinding and debriefing were embodied, related to their goals in undertaking the study, and social (e.g., embedded in trusting and valued relationships with acupuncturists). We suggest ways in which debriefing to placebo allocation can be managed sensitively to facilitate positive outcomes for participants.


Massive vascular endothelium growth factor (VEGF) expression in Eales' disease.
Eales' disease is an idiopathic retinal vasculitic and vaso-occlusive process complicated by extensive retinal neovascularisation and vitreous hemorrhages. The great propensity to produce retinal neovessels is one of the particular aspects of the disease that deserves to be further investigated. We report a case of Eales' disease having evolved over more than three decades, with a typical clinical presentation in one eye, while the other eye had to be enucleated because of a terminal neovascular glaucoma, thus allowing pathological examination. The functional right eye was treated by vitrectomy, cerclage, cryocoagulation and endolaser. The non-functional phthitic left eye was enucleated and submitted for histopathological and immunohistochemical examination using antibodies against vascular endothelial growth factor, T-cells, B-cells and Müller cells. Evolution was favourable in the operated right eye, following management of the inflammatory reaction. The histopathological examination of the left eye revealed an occlusion of the anterior chamber angle by rubeosis iridis, tractional retinal detachments, pre-, intra- and sub-retinal neovascular membranes, and vitrous hemorrhages. Diffuse positive anti-VEGF immunostaining was found at the level of the retinal neovascular membranes. The retina exhibited prominent Müller cell immunostaining, indicating extensive gliosis, and predominantly B cell infiltrates were found in the eye. The present study indicates a close relationship between the prominent neovascular proliferation in Eales' disease and the intense expression of VEGF. The increased expression of VEGF, when compared to other conditions inducing neovascularisation, might explain the severity of neovascular growth and the propensity of repeated vitrous hemorrhages in Eales' disease.


An evaluation of a community aged care nurse practitioner service.
An evaluation is presented that aimed to augment current understandings of the nurse practitioner role by investigating potential outcomes of a community aged care nurse practitioner (ACNP) service on clients and the health care team. In Australia, the nurse practitioner role is being implemented in a variety of health care settings and is characterized by extended practice: prescribing of medications, requests for diagnostic investigations, referral to medical specialists and admitting clients to inpatient facilities. An exploratory qualitative evaluation method through data collection by interview and thematic analysis was undertaken. All clients referred to the ACNP service between June and August 2003, and a convenience sample of health professionals, were invited to participate in individual semi-structured interviews. Findings suggested that an ACNP could provide a high quality of holistic nursing care and positively affect clients' physical and psychological symptom management, enhance clients' quality of life, assist with supplies, provide health education and assist with advocacy. Health professionals commented on effective collaboration with the ACNP service during their partnerships in client care provision. Overall, the positive effects of the ACNP service on clients and the health care team support the full implementation of the role within the community setting. Funding support for the nurse practitioner role is a vital addition to consideration in the development of international policy on advanced practice nursing. Without adequate funding, the full benefits of the nurse practitioner role in clinical practice, as suggested by the findings presented in this evaluation, will be compromised.


The team.
Aligning patient goals with treatment plans is an ongoing challenge in the current healthcare environment. Particularly in patients with multiple comorbidities and terminal illness, this planning is even more important. This poem, which tells the story of a dying patient, highlights the significance of prioritizing patient values and the teamwork it often takes to achieve patient goals. In this case, the patient's goal was to make it to his granddaughter's wedding and give a special toast at the reception. A team of healthcare professionals assembled and attempted to align our objectives with his, and this poem tells of that journey.


USP10 promotes the progression of triple-negative breast cancer by enhancing the stability of TCF4 protein.
Investigating the role of ubiquitin-specific peptidase 10 (USP10) in triple-negative breast cancer (TNBC). Analyzed USP10 expression levels in tumors using public databases. Detected USP10 mRNA and protein levels in cell lines. Examined USP10 expression in tumor tissues from breast cancer patients. Conducted USP10 knockdown experiments and analyzed changes in cell proliferation and metastasis. Confirmed protein-protein interactions with USP10 through mass spectrometry, Co-IP, and fluorescence experiments. Assessed impact of USP10 on transcription factor 4 (TCF4) ubiquitination and validated TCF4's influence on TNBC cells. We initially identified a pronounced overexpression of USP10 across multiple tumor types, including TNBC. Subsequently, we observed a conspicuous upregulation of USP10 expression levels in breast cancer cell lines compared to normal breast epithelial cells. However, upon subsequent depletion of USP10 within cellular contexts, we noted a substantial attenuation of malignant proliferation and metastatic potential in TNBC cells. In subsequent experimental analyses, we elucidated the physical interaction between USP10 and the transcription factor TCF4, whereby USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC. Collectively, this study demonstrates that USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC.


A self-illuminating nanoparticle for inflammation imaging and cancer therapy.
Nanoparticles have been extensively used for inflammation imaging and photodynamic therapy of cancer. However, the major translational barriers to most nanoparticle-based imaging and therapy applications are the limited depth of tissue penetration, inevitable requirement of external irradiation, and poor biocompatibility of the nanoparticles. To overcome these critical limitations, we synthesized a sensitive, specific, biodegradable luminescent nanoparticle that is self-assembled from an amphiphilic polymeric conjugate with a luminescent donor (luminol) and a fluorescent acceptor [chlorin e6 (Ce6)] for in vivo luminescence imaging and photodynamic therapy in deep tissues. Mechanistically, reactive oxygen species (ROS) and myeloperoxidase generated in inflammatory sites or the tumor microenvironment trigger bioluminescence resonance energy transfer and the production of singlet oxygen (1O2) from the nanoparticle, enabling in vivo imaging and cancer therapy, respectively. This self-illuminating nanoparticle shows an excellent in vivo imaging capability with suitable tissue penetration and resolution in diverse animal models of inflammation. It is also proven to be a selective, potent, and safe antitumor nanomedicine that specifically kills cancer cells via in situ 1O2 produced in the tumor microenvironment, which contains a high level of ROS.


Aging affects motor learning but not savings at transfer of learning.
Two important components of skill learning are the learning process itself (motor acquisition) and the ability to transfer what has been learned to new task variants (motor transfer). Many studies have documented age-related declines in the ability to learn new manual motor skills. In this study, I tested whether the degree of savings at transfer of learning is similarly affected by advancing age. Young and older adults made aiming movements with a joystick to hit targets presented on a computer screen, with real-time feedback display of their movement. They adapted to three different rotations of the feedback display in a sequential fashion, with return to the normal feedback display between each. Adaptation performance was better when it was preceded by other adaptive experiences, regardless of age.


Multifunctional nanoparticles of paclitaxel and cyclodextrin-polypeptide conjugates with in vitro anticancer activity.
In this study, the cyclodextrin polypeptide (R8-CMβCD) was successfully synthesized by the conjugation of a cell-penetrating peptide (R8) with carboxymethyl-β-cyclodextrin (CMβCD) via the carbon diamine reaction. Then, paclitaxel-loaded nanoparticles (PTX@R8-CMβCD NPs) was prepared. Results of transmission electron microscopy (TEM) showed that PTX@R8-CMβCD NPs were spherical with smooth surfaces and an average diameter about 144 nm. The amount of PTX released from NPs was less than 20% at pH7.4, but it increased significantly to 80% in the weakly acidic cytoplasm of tumors (pH5.0). Furthermore, PTX@R8-CMβCD NPs promoted the cellular uptake of PTX. Further studies on the mechanism showed that cellular uptake of PTX@R8-CMβCD NPs could rely on multiple pathways. In addition, the NPs had the ability to inhibit P-gp efflux pumps. Cytotoxicity tests showed that the NPs had no side effects. Taken together, PTX@R8-CMβCD NPs is an effective anticancer drug delivery system, and the material (R8-CMβCD) may be a promising anti-cancer drug carrier.


A New Stimulation Mode for Deep Brain Stimulation in Parkinson's Disease: Theta Burst Stimulation.
The purpose of this study was to assess efficacy and safety of a new patterned theta burst stimulation algorithm of DBS with the aim of expanding the therapeutic window and clinical benefit in PD. In this single-center, randomized, double-blind, clinical short-term trial, unilateral conventional subthalamic DBS was compared with unilateral patterned stimulation algorithms with intraburst high- or low-frequency theta burst stimulation in 17 PD patients. There were no serious adverse events with theta burst stimulation. During monopolar review, conventional subthalamic DBS and high-frequency theta burst stimulation were comparable, but low-frequency theta burst stimulation differed by requiring higher stimulation amplitudes for symptom reduction, but a larger therapeutic window. High- and low-frequency theta burst stimulation with adapted stimulation amplitude were effective in PD symptom reduction with differential effects on akinesia and tremor, depending on the theta burst stimulation mode. Theta burst stimulation is a safe and effective stimulation mode with potential future application opportunities. © 2020 International Parkinson and Movement Disorder Society.


Forecasting Chronic Diseases Using Data Fusion.
Data fusion, that is, extracting information through the fusion of complementary data sets, is a topic of great interest in metabolomics because analytical platforms such as liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy commonly used for chemical profiling of biofluids provide complementary information. In this study, with a goal of forecasting acute coronary syndrome (ACS), breast cancer, and colon cancer, we jointly analyzed LC-MS, NMR measurements of plasma samples, and the metadata corresponding to the lifestyle of participants. We used supervised data fusion based on multiple kernel learning and exploited the linearity of the models to identify significant metabolites/features for the separation of healthy referents and the cases developing a disease. We demonstrated that (i) fusing LC-MS, NMR, and metadata provided better separation of ACS cases and referents compared with individual data sets, (ii) NMR data performed the best in terms of forecasting breast cancer, while fusion degraded the performance, and (iii) neither the individual data sets nor their fusion performed well for colon cancer. Furthermore, we showed the strengths and limitations of the fusion models by discussing their performance in terms of capturing known biomarkers for smoking and coffee. While fusion may improve performance in terms of separating certain conditions by jointly analyzing metabolomics and metadata sets, it is not necessarily always the best approach as in the case of breast cancer.


Cemiplimab- and nivolumab-induced myasthenia gravis: two clinical cases.
Immune-related myasthenia gravis is a rare, disabling, and potentially fatal adverse event of immune checkpoint inhibitor treatment. It is important to identify and manage it promptly. We present two cases of immune-related de novo myasthenia gravis observed at the Modena Cancer Center in two elderly patients treated with two anti-PD-1 monoclonal antibodies: cemiplimab and nivolumab.


Inferring human neutral genetic variation from craniodental phenotypes.
There is a growing consensus that global patterns of modern human cranial and dental variation are shaped largely by neutral evolutionary processes, suggesting that craniodental features can be used as reliable proxies for inferring population structure and history in bioarchaeological, forensic, and paleoanthropological contexts. However, there is disagreement on whether certain types of data preserve a neutral signature to a greater degree than others. Here, we address this unresolved question and systematically test the relative neutrality of four standard metric and nonmetric craniodental data types employing an extensive computational genotype-phenotype comparison across modern populations from around the world. Our computation draws on the largest existing data sets currently available, while accounting for geographically structured environmental variation, population sampling uncertainty, disparate numbers of phenotypic variables, and stochastic variation inherent to a neutral model of evolution. Our results reveal that the four data types differentially capture neutral genomic variation, with highest signals preserved in dental nonmetric and cranial metric data, followed by cranial nonmetric and dental metric data. Importantly, we demonstrate that combining all four data types together maximizes the neutral genetic signal compared with using them separately, even with a limited number of phenotypic variables. We hypothesize that this reflects a lower level of genetic integration through pleiotropy between, compared to within, the four data types, effectively forming four different modules associated with relatively independent sets of loci. Therefore, we recommend that future craniodental investigations adopt holistic combined data approaches, allowing for more robust inferences about underlying neutral genetic variation.


Differential inactivation of Escherichia coli membrane dehydrogenases by a myeloperoxidase-mediated antimicrobial system.
Neutrophil myeloperoxidase, hydrogen peroxide, and chloride constitute a potent antimicrobial system with multiple effects on microbial cytoplasmic membranes. Among these is inhibition of succinate-dependent respiration mediated, principally, through inactivation of succinate dehydrogenase. Succinate-dependent respiration is inhibited at rates that correlate with loss of microbial viability, suggesting that loss of respiration might contribute to the microbicidal event. Because respiration in Escherichia coli can be mediated by dehydrogenases other than succinate dehydrogenase, the effects of the myeloperoxidase system on other membrane dehydrogenases were evaluated by histochemical activity stains of electrophoretically separated membrane proteins. Two bands of succinate dehydrogenase activity proved the most susceptible to inactivation with complete loss of staining activity within 20 min, under the conditions employed. A group with intermediate susceptibility, consisting of lactate, malate, glycerol-3-phosphate, and dihydroorotate dehydrogenases as well as three bands of glucose-6-phosphate dehydrogenase, was almost completely inactivated within 30 min. The relatively resistant group, including the dehydrogenases for glutamate, NADH, and NADPH and the remaining bands of glucose-6-phosphate dehydrogenase, retained substantial amounts of diaphorase activity for up to 60 min of incubation with the myeloperoxidase system. The differential effects of myeloperoxidase on dehydrogenase inactivation could not be correlated with published enzyme contents of flavin or iron-sulfur centers, potential targets of myeloperoxidase-derived oxidants. Despite the relative resistance of NADH dehydrogenase/diaphorase activity to myeloperoxidase-mediated inactivation, electron transport particles prepared from E. coli incubated for 20 min with the myeloperoxidase system lost 55% of their NADH oxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Soft, Bistable Actuators for Reconfigurable 3D Electronics.
Existing strategies for reconfigurable three-dimensional (3D) electronics are greatly constrained by either the complicated driven mechanisms or harsh demands for conductive materials. Developing a simple and robust strategy for 3D electronics reconstruction and function extension remains a challenge. Here, we propose a solvent-driven bistable actuator, which acts as a substrate to reconstruct the combined 3D electronic device. Extraction of silicon oil from a hybrid poly(dimethylsiloxane) (PDMS) circle sheet buckles the dish to a bistable structure. The ultraviolet (UV)/ozone treatment on one surface of the PDMS structure introduces an oxidized layer, yielding a bilayered, solvent-driven bistable smart actuator. The snap-back stimulus to the oxidized layer differs from the snap-through stimulus. Experimental and numerical studies reveal the fundamental regulations for buckling configurations and the bistable behavior of the actuator. The prepared bistable actuator drives the bonded kirigami polyimide (PI) sheets to diverse 3D structures from the original bending configuration, reversibly. A frequency-reconfigurable electrically small monopole antenna is presented as a demonstration, which paves a way for the applications of this actuator in the field of reconfigurable 3D electronics.


Vortices in the wake of a femtosecond laser filament.
We report on the experimental observation of fluid flow caused by propagation of femtosecond filaments in dry air. We find that the ionization of the medium deposits a non-negligible amount of heat, which creates vortices in a semi-confined glass cylinder. We confirm the influence of thermal gradients on vortex formation by the use of a heated wire in a similar configuration.


Risk factors for adolescent pregnancy in Bogotá, Colombia, 2010: a case-control study.
To identify risk factors for adolescent pregnancy among female students in Bogotá, Colombia. This was a retrospective study of cases and controls matched by age, identified by means of a survey on the sexual behavior of adolescent students in Bogotá (Encuesta sobre el Comportamiento Sexual de los Adolescentes Escolarizados en Bogotá) conducted in the first semester of 2010. All 272 cases and 544 randomly-selected controls were taken from 39 044 total records. Variables considered were sociodemographics, household structure, and family environment; sexual relationships and pregnancy; and knowledge of sexual and reproductive health. Matching and conditional logistic regression were used to adjust for possible confounding factors. The factors associated with increased risk of adolescent pregnancy based on multivariate analyses were: attending public school (odds ratio [OR]=2.25; 95% confidence interval [95% CI]: 1.45-3.51); history of siblings with adolescent pregnancy (OR =1.98; 95% CI: 1.55-2.76); early first sexual intercourse (12 years of age or less) (OR =2.34; 95% CI: 1.01-5.40); having a self-reported low- or average-level of contraceptive knowledge (OR =3.92; 95% CI: 1.96-7.83); previous pregnancy (OR =14.09; 95% CI: 8.74- 22.70); and not living with both parents (OR 3.58; 95% CI: 2.10-6.16). Factors related to individual, family, and social environments that influence the incidence of adolescent pregnancy must be considered and addressed when designing interventions. The existing sex education curriculum is an important component in preventing adolescent pregnancy, however, parent/caregiver participation is required for success.


Is there a functional correlate of Kv1.5 in the ventricle of canine heart and what would it mean for the use of I(Kur) blockers?
The cardiac ultrarapid outward current I(Kur), encoded by KCNA5, is of special pharmacological interest, because it is considered to be atrium-specific. I(Kur) has therefore become a target in the therapy of atrial tachyarrhythmias. However, the concept of atrium specificity is only valid if a functional I(Kur) current is in fact absent from the ventricle. However, new work has detected a I(Kur)-like current in canine ventricular myocytes, sensitive to 4-aminopyridine and suppressed by the I(Kur) blocker DPO-1, findings that support the existence of a functional ventricular I(Kur). These indications are, however, indirect and more effort is needed to clarify unequivocally the putative role of an expectedly small I(Kur) component in the ventricle.


Changing concepts of deep venous thrombosis of the upper extremity--report of a series and review of the literature.
Deep venous thrombosis (DVT) of the upper extremity has recently been recognized as being more common than previously reported (probably because of the increasingly frequent use of subclavian venous access). A retrospective review of patients in whom subclavian or axillary DVT had developed in the past 6 years (1980 to 1986) was conducted at the Akron General Medical Center. The major cause identified was related to subclavian venous catheterization, which accounted for 39% of all instances of subclavian and axillary DVT. Our results are correlated with a review of the literature. In our review of studies in which subclavian venous catheterizations were prospectively examined with use of objective means of diagnosis, we found that 28% of all subclavian catheterizations had venous thrombosis develop, often subclinically. This is not an innocuous disease, as suggested in the past; in our series 12% of upper-extremity DVT had pulmonary embolization (PE). In reviewing the recent literature, we found an average 12.4% incidence of PE, which often occurs during anticoagulation treatment. Diagnostic modalities are discussed and treatment regimens are reviewed along with an extensive literature review.


Eltrombopag-induced liver dysfunction during the treatment of immune thrombocytopenia and its risk factors.
Eltrombopag is an effective oral thrombopoietin receptor agonist for the treatment of immune thrombocytopenia (ITP). A common adverse reaction is liver dysfunction. This study aimed to investigate early liver dysfunction during eltrombopag treatment of ITP and risk factors. We retrospectively analyzed liver dysfunction in patients receiving eltrombopag at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2019 and December 2020. Patients were divided into two groups, those with and without liver dysfunction after eltrombopag treatment. Clinical characteristics of the two groups of patients, including sex, age, body mass index (BMI), comorbidities, concomitant medications, prophylactic use of hepatoprotective drugs, and eltrombopag usage were analyzed to identify the risk factors of liver dysfunction. A total of 85 patients were included in this study, including 28 men and 57 women aged 44±17 years with a BMI of 25.1±3.57 kg/m2. After eltrombopag treatment, liver dysfunction occurred in 19 patients (22.4%), mainly in the form of elevated alanine aminotransferase (ALT; n=10, 11.8%) and total blood bilirubin (TBIL; n=11, 12.9%). Among patients with liver dysfunction, 73.7% had grade 1, 15.8% had grade 2, and 10.5% had grade 3. There were 7 cases (8.2%) of drug-induced hepatocellular injury, of which 6 cases (85.7%) were mild and 1 (14.3%) was moderate. No significant between-group difference was observed in sex, age, BMI, use of other drugs that can induce liver dysfunction, prophylactic use of hepatoprotective drugs, or initial dose, usage time, or cumulative dose of eltrombopag (all P>0.05). Comorbid type 2 diabetes or noninflammatory hepatobiliary disease (gallbladder stones, gallbladder polyps, liver cysts, fatty liver) was significantly correlated with liver dysfunction (P=0.04, P=0.023, respectively). The risk of early liver dysfunction, while mild to moderate in most cases, is high in patients with ITP on eltrombopag treatment, especially in those with type 2 diabetes and hepatobiliary diseases. Therefore, patients should be closely monitored during treatment to enable timely intervention as needed.


The colonic interleukin-19 aggravates the dextran sodium sulfate/stress-induced comorbidities due to colitis and anxiety.
Comorbidities due to inflammatory bowel disease (IBD) and anxiety are commonly acknowledged; however, their underlying basis is unclear. In the current study, we first conducted a clinical retrospective analysis to identify the enhancive incidence rate of IBD before or after the epidemic of Corona Virus Disease 2019 (COVID-19), with higher Generalized Anxiety Disorder-7 (GAD-7), as well as poorer Gastrointestinal Quality of Life Index (GIQLI). Then, the dextran sodium sulfate (DSS) and chronic unpredictable stress (CUS)-induced IBD and anxiety comorbid models were established with the correlational relations between symptoms of IBD and anxiety-related behaviors. We found dysfunctional up-regulation of a new inflammatory factor interleukin (IL)-19 in the colon of DSS/CUS treated mice. Overexpression of IL-19 in colon induced anxious phenotypes, and accelerated the anxious condition and symptoms of colitis in the DSS/CUS model by promoting the expression of inducible nitric oxide synthase (iNOS), IL-1β, and IL-6 pro-inflammatory factors, and activating signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon. Furthermore, overexpression of IL-19 in the colon also reduced the expression levels of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), and cAMP-response element binding protein (CREB) signaling pathways activity in the hippocampus. These results suggest that IL-19 was a pivotal player in DSS/CUS-induced comorbidities of colitis and anxiety with different signaling pathways for the colon and hippocampus, which provides a candidate gene to explore the pathophysiology of comorbidities due to colitis and anxiety.


Origin and Evolution of the Kiwifruit Canker Pandemic.
Recurring epidemics of kiwifruit (Actinidia spp.) bleeding canker disease are caused by Pseudomonas syringae pv. actinidiae (Psa). In order to strengthen understanding of population structure, phylogeography, and evolutionary dynamics, we isolated Pseudomonas from cultivated and wild kiwifruit across six provinces in China. Based on the analysis of 80 sequenced Psa genomes, we show that China is the origin of the pandemic lineage but that strain diversity in China is confined to just a single clade. In contrast, Korea and Japan harbor strains from multiple clades. Distinct independent transmission events marked introduction of the pandemic lineage into New Zealand, Chile, Europe, Korea, and Japan. Despite high similarity within the core genome and minimal impact of within-clade recombination, we observed extensive variation even within the single clade from which the global pandemic arose.


Cancer management challenge in a developing country in COVID-19 pandemic: reflection of a group of Moroccan oncologists.
Management of cancer patients during the COVID-19 pandemic is a worldwide challenge - in particular in developing countries where the risk of saturation of health facilities and intensive care beds must be minimized. The first case of COVID-19 was declared in Morocco on 2 March 2020, after which a panel of Moroccan experts, consisting of medical oncologists from universities and regional and private oncology centers, was promptly assembled to conduct a group reflection on cancer patient's management. The main objective is to protect the immunocompromised population from the risk of COVID-19, while maintaining an adequate management of cancer, which can quickly compromise their prognosis. Recommendations are provided according to each clinical situation: patients undergoing treatment, new cases, hospitalized patients, palliative care and surveillance.


Extraction Efficiency and Alpha-Glucosidase Inhibitory Activities of Green Tea Catechins by Different Infusion Methods.
Alpha-glucosidase is an important target for glycemic control with the aim of reducing the risk of type 2 diabetes (T2D). Green tea catechins have been reported to inhibit alpha-glucosidase activity as a potential beverage to control blood glucose levels. However, the effects of the daily infusion style of green tea on tea catechins and their activity remain unclear. In this study, the extraction efficiency of catechins was investigated for 12 green tea extracts (GTEs) infused with 70% ethanol (70% EtOH for 24 h, a favored solvent for catechin extraction), room temperature water infusion (RT H2O for 24 h, an easy way to drink tea), and hot water infusion (Hot H2O for 90 s, a standard way to drink tea). Eight catechins were quantified by HPLC, and the inhibitory effect of GTEs and their catechins on alpha-glucosidase was measured with both rat intestinal enzymes and human Caco-2 cells. The inhibitory mechanism was further analyzed in silico by docking catechins to human alpha-glucosidase using Molecular Operating Environment software. The results showed that total catechins and gallate catechins were efficiently extracted in the order of 70% EtOH, RT H2O, and Hot H2O, and the inhibitory activity against alpha-glucosidase also followed a similar order. Pearson correlation analysis indicated that the alpha-glucosidase inhibitory activity of GTEs was significantly positively correlated with the contents of total catechins, especially gallate catechins. Gallate catechins, such as EGCg and ECg, showed lower IC50 values than free catechins for the enzyme in both rats and humans. In silico simulation revealed that gallate catechins were bound to the different sites with free catechins, and the docking energy of gallate catechins was lower than that of free catechins. Taken together, our data indicated that the daily infusion style of green tea significantly impacted the extraction efficiency and alpha-glucosidase inhibitory activities of catechins, which will give us insight into the use of green tea catechins for glycemic control through efficient infusion.


A Multimodal Score Accurately Classifies Fontan Failure and Late Mortality in Adult Fontan Patients.
Despite the outstanding success of the Fontan operation, it is a palliative procedure and a substantial number of patients experience late failure of the Fontan circulation. Clinical presentation and hemodynamic phenotypes of Fontan failure are considerably variable. While various parameters have been identified as risk factors for late Fontan failure, a feasible score to classify Fontan failure and possibly allow timely risk stratification is lacking. Here, we explored the possibility of developing a score based on hemodynamic, clinical and laboratory parameters to classify Fontan failure and mortality. We performed a retrospective study in our cohort of adult Fontan patients from two institutions [n = 198, median follow-up after Fontan 20.3 (IQR 15.6-24.3) years], identifying those patients with clinical Fontan failure (n = 52, 26.3%). Various hemodynamic, echocardiographic, laboratory and clinical data were recorded and differences between patients with and without Fontan failure were analyzed. We composed a Fontan Failure Score containing 15 parameters associated with Fontan failure and/or mortality and assessed its accuracy to discriminate between patients with and without late Fontan failure as well as late mortality and survival. Late failure occurred at a median of 18.2 (IQR 9.1-21.1) years after Fontan completion. Mortality associated with Fontan failure was substantial (25/52, 48.1%) with freedom of death/transplantation/take-down of 64% at 5 years and 36% at 10 years after onset of Fontan failure, respectively. Patients with Fontan failure had a significantly higher median Fontan Failure Score compared to non-failing Fontan patients [8 points (IQR 5-10) vs. 2 points (IQR 1-5), p < 0.001]. The score accurately classifies Fontan failure as well as mortality as assessed with receiver operating characteristic analysis. Area under the curve of the Fontan Failure Score was 0.963 (95% CI 0.921; 0.985, p < 0.001) to discriminate failure and 0.916 (95% CI 0.873; 0.959, p < 0.001) to classify mortality. We have developed an uncomplex yet remarkably accurate score to classify Fontan failure and late mortality in adult Fontan patients. Prospective validation and most likely refinement and calibration of the score in larger and preferably multi-institutional cohorts is required to assess its potential to predict the risk of Fontan failure and late mortality.


Longitudinal Psychiatric Symptoms in Prodromal Huntington's Disease: A Decade of Data.
Psychiatric symptoms are a significant aspect of Huntington's disease, an inherited neurodegenerative illness. The presentation of these symptoms is highly variable, and their course does not fully correlate with motor or cognitive disease progression. The authors sought to better understand the development and longitudinal course of psychiatric manifestations in individuals who carry the Huntington's disease mutation, starting from the prodromal period prior to motor diagnosis. Longitudinal measures for up to 10 years of psychiatric symptoms from the Symptom Checklist-90-Revised were obtained from 1,305 participants (1,007 carrying the Huntington's disease mutation and 298 without [classified as controls]) and 1,235 companions enrolled in the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) study. Participants with the mutation were stratified into three groups according to probability of motor diagnosis within 5 years. Using linear mixed-effects regression models, differences in psychiatric symptoms at baseline and over time between the mutation-positive groups and the controls were compared, as well as between ratings by mutation-positive participants and their companions. Nineteen of 24 psychiatric measures (12 participant ratings and 12 companion ratings) were significantly higher at baseline and showed significant increases longitudinally in the individuals with the Huntington's disease mutation compared with controls. The differences were greatest in comparisons of symptom reports from companions compared with self-reports, especially in participants who were closest to motor diagnosis. The results indicate that psychiatric manifestations develop more often than previously thought in the Huntington's disease prodrome. Symptoms also increase with progression of disease severity. Greater symptom ratings by companions than by mutation-positive participants suggest decreasing awareness in those affected.


Lichen sclerosus: treatment and follow-up at the departments of gynaecology and dermatology.
To compare the treatment and follow-up of patients with lichen sclerosus (LS) at the departments of Gynaecology and Dermatology at the Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands, to evaluate the need for a multidisciplinary vulvar clinic. Treatment and follow-up data of all women with histologically proven (between January 1995 and January 2001) anogenital LS visiting the outpatient clinics of the departments of Obstetrics & Gynaecology and Dermatology were collected (last date of follow-up: January 2008). Eighty-four patients with LS were included in this study, 10 patients (12%) of which were treated by both specialties. At the Gynaecology department, LS patients more often received surgical treatment, topical estrogens, and lidocaine ointment, whereas at the Dermatology department, local class 2/3 corticosteroids were more often prescribed. Follow-up frequencies were similar in both specialties and took place at 3 to 4 visits in the first year and at least once a year afterward. One patient developed vulvar squamous cell carcinoma. This patient had withdrawn from follow-up and had her condition diagnosed with carcinoma 74 months after the LS had been diagnosed. Although no hospital guidelines existed, management of patients with LS agreed with current recommendations in the literature, although differences in secondary and supportive therapy existed owing to differences in expertise. The relatively high percentage of patients treated by both specialties with a high frequency of visits emphasizes the need for a multidisciplinary clinic for vulvar disease.


Vascular calcification in ex vivo carotid specimens: precision and accuracy of measurements with multi-detector row CT.
To test the accuracy and precision of multi-detector row computed tomography (CT)-derived measurements of vascular calcification in ex vivo human carotid endarterectomy (CEA) specimens. Sixteen ex vivo CEA specimens were imaged with multi-detector row CT. Multi-detector row CT-derived calcium scoring algorithms (ie, mineral mass and volume score) were compared with the mass and volume of ashed remnants of the CEA specimens. Bland-Altman analysis was performed to assess the mean (ie, bias) and SD (ie, precision) of differences between multi-detector row CT- and ashing-derived measurements. In addition, conventional Agatston score, volume score, mineral mass, and modified Agatston score were calculated for each specimen by using a number of scanning protocols. Images were obtained at a section thickness of 1.25 mm by using different tube energy settings and tube currents. Specimens were also imaged at different section thicknesses with fixed combinations of tube energy and tube current. To compare measurement variability of scoring methods, coefficients of variation for all protocols were calculated. Both mean multi-detector row CT-derived mineral mass and mean ashing-derived mineral mass were 0.129 g +/- 0.173 (r = 0.99, P <.001). Mean multi-detector row CT- and ashing-derived volumes were 339.94 mm3 +/- 395.4 and 39.48 mm3 +/- 55.76, respectively (r = 0.95, P <.001). Measurement bias relative to the reference ashing values was high (2,800.0%) for volume score and low (2.58%) for mineral mass. Measurement precision was 0.6% for volume score and greater than 0.0005% for mineral mass. Mean coefficients of variation for all CT protocols were 5.0% +/- 4.2 and 4.9% +/- 4.2 for mineral mass and modified Agatston score, respectively, and 16.0% +/- 9.2 and 14.5% +/- 3.9 for conventional Agatston and volume scores, respectively (P <.001). Compared with the conventional volume score, multi-detector row CT-derived mineral mass is a less biased and more precise measurement of the mineral content of nonmoving ex vivo CEA specimens. Mineral mass and modified Agatston score are more reproducible than conventional volume and Agatston scores.


[Effects of fibroblasts on the proliferation and migratory capacity of renal cell carcinoma cell lines and sensitivity to everolimus].
To observe the effects of normal human renal fibroblast (NHRF) on renal cell carcinoma cell lines. Renal cell carcinoma (RCC) cell lines 786-O and Caki-1 were co-cultured with NHRF for assessing the proliferation and migratory capacities of renal cell carcinoma cell lines and the sensitivity to everolimus. Co-culturing with NHRF substantially increased the proliferation capacity of both RCC cell lines (786-O: 2.35 ± 0.05 vs1.93 ± 0.15, P = 0.01;Caki-1: 2.35 ± 0.21 vs 1.24 ± 0.11, P = 0.001). Similarly the migratory capacities of both cell lines became significantly enhanced after co-culturing (786-O: 1.53 ± 0.11 vs 0.98 ± 0.11, P = 0.04; Caki-1: 1.53 ± 0.11vs 0.98 ± 0.11, P = 0.04) compared with untreated control. Furthermore, the sensitivities of both cell lines to everolimus (1, 5, 10 µmol/L) dramatically decreased in those pre-co-cultured with NHRF (786-O:P value 0.04, 0.35, 0.18); Caki-1: P value 0.02, 0.03, 0.024). NHRF promotes the proliferation and migration capacities of 786-O and Caki-1. And it may be involved in the resistance of RCC to everolimus.


[Surgical treatment of dumbbell tumor complicating with vertebral destruction in cervical spine].
To explore the feasibility and efficacy of operating through an anterior approach in the treatment of dumbbell tumor complicating with vertebral destruction in cervical spine. Surgical procedures were performed through an anterior approach in 7 cases of dumbbell tumor complicating with vertebral and transverse process destruction during the period of May 2004 to February 2009. Bone graft and internal fixation were implemented after tumor removal. In all 7 cases, tumors were resected completely and no recurrence occurred during a follow-up period of 6-46 months. The symptoms improved greatly postoperatively with fine fusion of graft bone. There was neither loose plate nor cervical instability. For huge dumbbell tumor with damaged vertebral body and transverse process in cervical spine, the anterior approach operation will remove tumor entirely and restore the stability of cervical spine so as to prevent spinal cord injury. It is an excellent option of treating dumbbell tumor in cervical spine.


Characteristics of vasopressin release during controlled reduction in arterial pressure.
Because of the interruption of the descending sympathetic nervous pathways, individuals with cervical spinal cord injury experience orthostatic hypotension when in an upright posture. The changes in hemodynamic parameters that occur during upright posture can be closely monitored and quantitated during progressive head-up tilting on a tilt table. We have utilized this method to assess the response of vasopressin and other vasoactive hormones to gradual, progressive reductions in arterial pressure and to identify possible threshold responses to baroreceptor stimulation in human subjects. Studies were performed in 12 quadriplegic subjects, 3 paraplegic subjects, and 3 normal control subjects. Data from the studies in paraplegic and normal subjects did not differ and were pooled as control data. In quadriplegic subjects, mean arterial pressure (MAP) decreased from 93 +/- 4 mm Hg to 60 +/- 3 mm Hg in a closely correlated (r = 0.948, p < 0.002) linear relationship with increasing degrees of tilt, whereas in control subjects, MAP increased from 81 +/- 4 to 88 +/- 3 mm Hg. Plasma vasopressin concentrations (Pavp) increased minimally in quadriplegic subjects until MAP was reduced to levels that were 25% to 30% lower than MAP with subjects in the supine posture. Beyond this level of hypotension, Pavp increased markedly. Log-linear regression analysis of these data showed a highly significant correlation (r = 0.85, p < 0.0002) between in Pavp and MAP, which defines Pavp as an exponential function of decreasing MAP. Changes in Pavp in control subjects were minimal during incremental head-up tilting. In contrast, plasma renin activity (PRA) increased in both quadriplegic and control subjects. Log-linear regression analysis of these data showed highly significant correlates between in PRA and degree of tilt in both quadriplegic (r = 0.958, p < 0.0002) and control (r = 0.873, p < 0.0002) subjects. Plasma atrial natriuretic peptide concentrations decreased linearly with increasing degrees of tilt. The rate of decline in Panp was greater in quadriplegic than in control subjects. These studies provide additional evidence that Pavp increases exponentially as a function of decreasing MAP and suggest that a critical threshold level of hypotension exists at which vasopressin release accelerates rapidly in response to baroreceptor stimulation. At this level of reduced MAP, Pavp reaches levels that are potentially capable of exerting a pressor effect.


The identification of switch-like alternative splicing exons among multiple samples with RNA-Seq data.
Alternative splicing is an ubiquitous phenomenon in most human genes and has important functions. The switch-like exon is the type of exon that has a high level of usage in some tissues, but has a low level of usage in the other tissues. They usually undergo strong tissue-specific regulations. There is still a lack a systematic method to identify switch-like exons from multiple RNA-seq samples. We proposed a novel method called iterative Tertile Absolute Deviation around the mode (iTAD) to profile the distribution of exon relative usages among multiple samples and to identify switch-like exons and other types of exons using a robust statistic estimator. We validated the method with simulation data, and applied it on RNA-seq data of 16 human body tissues and detected 3,100 switch-like exons. We found that switch-like exons tend to be more associated with Alu elements in their flanking intron regions than other types of exons.


Standard method for ultrasound imaging of coronary artery in children.
The Child Coronary Arterial Diameter Reference Study Group of the Japan Kawasaki Disease Society recommends ultrasound imaging as the standard method for measuring the diameter of the coronary artery in children. The patient is examined in a supine or right decubitus position by using a sector probe (≥ 5 MHz). The coronary arterial diameter measured at the minimum gain setting is the distance between the internal echo edge and the internal echo edge. The diameter is measured during the early diastolic phase at the end of the T wave. The left main coronary artery and the proximal right coronary artery are approached from the precordial short axis at the level of the aortic valve. The proximal and mid-right coronary arteries are observed on the atrioventricular groove, anterior to the tricuspid valve ring. The right coronary artery of the acute margin of the heart runs along the right side of the tricuspid valve ring. The distal right coronary artery is observed on the posterior atrioventricular groove, and the posterior descending branch of the right coronary artery is observed on the posterior interventricular groove. The right coronary artery is also well observed from the right sternal border in the right decubitus position. Proximal and mid-anterior descending arteries are observed on the anterior interventricular groove. The proximal left circumflex coronary artery is observed in the atrioventricular groove, anterior to the mitral valve ring.


INBREEDING DEPRESSION IN GYNODIOECIOUS LOBELIA SIPHILITICA: AMONG-FAMILY DIFFERENCES OVERRIDE BETWEEN-MORPH DIFFERENCES.
If inbreeding depression is caused by deleterious recessive alleles, as suggested by the partial dominance hypothesis, a negative correlation between inbreeding and inbreeding depression is predicted. This hypothesis has been tested several times by comparisons of closely related species or comparisons of populations of the same species with different histories of inbreeding. However, if one is interested in whether this relationship contributes to mating-system evolution, which occurs within populations, comparisons among families within a population are needed; that is, inbreeding depression among individuals with genetically based differences in their rate of selfing should be compared. In gynodioecious species with self-compatible hermaphrodites, hermaphrodites will have a greater history of potential inbreeding via both selfing and biparental inbreeding as compared to females and may therefore express a lower level of inbreeding depression. We estimated the inbreeding depression of female and hermaphrodite lineages in gynodioecious Lobelia siphilitica in a greenhouse experiment by comparing the performance of selfed and outcrossed progeny, as well as sibling crosses and crosses among subpopulations. We did not find support for lower inbreeding depression in hermaphrodite lineages. Multiplicative inbreeding depression (based on seed germination, juvenile survival, survival to flowering, and flower production in the first growing season) was not significantly different between hermaphrodite lineages (δ = 0.30 ± 0.08) and female lineages (δ = 0.15 ± 0.18), although the trend was for higher inbreeding depression in the hermaphrodite lineages. The population-level estimate of inbreeding depression was relatively low for a gynodioecious species (δ = 0.25) and there was no significant inbreeding depression following biparental inbreeding (δ = 0.01). All measured traits showed significant variation among families, and there was a significant interaction between family and pollination treatment for four traits (germination date, date of first flowering, number of flowers, and aboveground biomass). Our results suggest that the families responded differently to selfing and outcrossing: Some families exhibited lower fitness following selfing whereas others seemed to benefit from selfing as compared to outcrossing. Our results support recent simulation results in that prior inbreeding of the lineages did not determine the level of inbreeding depression. These results also emphasize the importance of determining family-level estimates of inbreeding depression, relative to population-level estimates, for studies of mating-system evolution.


Synthesis of Azetidine Nitrones and Exomethylene Oxazolines through a Copper(I)-Catalyzed 2,3-Rearrangement and 4π-Electrocyclization Cascade Strategy.
A variety of azetidine nitrones are prepared in moderate to good yields through copper(I) combined with 2-aminopyridine to catalyze skeletal rearrangement of O-propargylic oximes. Mechanistic studies reveal that the reaction undergoes a copper(I)-catalyzed tandem [2,3]-rearrangement, 4π-electrocyclization, ring opening, and recyclization over four steps in one pot. Substituents at the terminus of alkyne and oxime moieties have a significant impact on the formation of azetidine nitrones and exomethylene oxazolines, respectively. Furthermore, the obtained azetidine nitrone could easily participate in [3 + 2] cycloaddition with alkynoates, and a [2.2]-paracyclophane-derived azetidine nitrone is synthesized in 45% yield over five steps from bromo[2.2]-paracyclophane.


Complication rate of transtemporal hydroxyapatite cement cranioplasties: a case series review of 76 cranioplasties.
The objective of this study was to evaluate the complication rate of transtemporal cranioplasties using hydroxyapatite cement (HAC) for repair. We conducted a retrospective case review of patients receiving HAC cranioplasties in the Acoustic Neuroma and Skull Base Surgery Program between July 1998 and December 2002. This study was conducted at a tertiary referral center. A total of 76 HAC cranioplasties were performed in 72 patients undergoing lateral skull base surgery. Patients undergoing anterior skull base surgery or those in which HAC was used for other reconstructive purposes were excluded from the study. We studied transtemporal approaches for otologic procedures requiring cranioplasty. Main outcomes measures consisted of complications requiring medical or surgical intervention. Of the 76 HAC cranioplasties, two cranioplasty grafts became infected, requiring explantation. The first case involved a wound infection that extended into and involved the HAC graft; the second involved seeding of the HAC graft after meningitis after a percutaneous, endoscopic gastrostomy tube placement performed several days after the primary skull base surgery. This gives our series a wound infection incidence rate of 1.3% and an overall complication incidence rate of 2.63%. This retrospective review provides the largest series to date evaluating the incidence of infection in HAC cranioplasties. Despite having a much larger series, our complication rate is the lowest published rate of HAC cranioplasty explantation, and the incidence of superficial wound infections reported here is consistent with the published data for neurosurgical and neurotologic procedures.


The deiodination of thyroxine in hyperthyroid rats as determined by renal clearance of iodide.
Other investigators have reported that whole body clearance of thyroxine (T4) is increased in hyperthyroid rats isotopically equilibrated with radioactive T4, using the 24 h post-injection serum T4 concentration in the clearance calculation. Data from this laboratory indicate that serum T4 concentration is lowest at this point yielding falsely high clearance values, particularly when high doses of T4 are injected. To investigate this problem further, two types of experiments were performed. First, rats were equilibrated with [125I]T4, 5 or 20 mug/day, and the urinary clearance of iodide derived from T4 (deiodinative clearance) was measured from 0-7 and 7-24 h after a T4 injection, using the T4 concentration in serum obtained at the midpoint of each urine collection period. Urine was then collected from the ureters for several 1 h periods during the 4th to 8th h following T4 injection, calculating clearances using the midpoint plasma T4 concentration. Second, normal rats were given a single dose of [125I]T4, 5 or 55 mug/rat, and deiodinative clearance was determined during the subsequent 0-7 and 7-24 h periods. The first experiment indicated that deiodinative clearance was significantly enhanced in rats equilibrated with the large dose of T4 under all conditions studied. In contrast, the clearance in normal rats given a single large dose of T4 was not significantly different from that of normal rats given a small dose of T4. These results support the view that T4 clearance is increased in hyperthyroidism, due in part to an increase in the deiodination of T4.


Nonadherence Behaviors and Some Related Factors in Kidney Transplant Recipients.
Kidney transplantation is the renal replacement therapy of choice for most patients with end-stage renal disease (ESRD), however, adherence to the recommended lifestyle is critical for a positive prognosis. The purpose of this study was to assess adherence to immunosuppressive therapy and lifestyle recommendations along with some related factors among kidney transplant patients. In this descriptive analytical study, all patients completed a questionnaire regarding medication intake and lifestyle recommendations (preventing of infection, self-monitoring, prevention of cardiovascular disease (CVD), and sun protection). The participants were divided into 4 groups according to the level of adherence (good, partial, poor, and nonadherent) indicated in their responses. Most kidney recipients were adherent to their drug prescriptions, but were partial, poor, or nonadherent regarding lifestyle recommendations. Increased passage of time since transplantation and low family support and educational level resulted in nonadherence. Men showed greater adherence to medication intake than women. Patients with lower number of drugs and reported drug side-effects illustrated better adherence to medication intake. Women adhered to infection protection recommendations more than men, and older and married patients adhered to cardiovascular prevention recommendations more than others. However, younger patients showed greater adherence to self-monitoring recommendations, and singles, young individuals, and women were adherent to sun protection recommendations. Nonadherence is common among kidney transplant recipients. Thus, it is necessary to determine patients who are at risk of nonadherence and to introduce more educational programs to improve their adherence and their quality of life (QOL).


Specificity and genetics of S-adenosylmethionine transport in Saccharomyces cerevisiae.
The specificity of a transport system for S-adenosylmethionine was determined through the use of structurally related derivatives. Of the compounds tested, the analogues S-adenosylethionine and S-inosylmethionine and the naturally occurring compounds S-adenosyl-(5')-3-methylthiopropylamine and S-adenosylhomocysteine competitively inhibited uptake of the sulfonium compound. Ki values for these compounds indicate that the order of affinity for the transport protein is S-adenosylmethionine congruent to S-adenosyl-(5')-3-methyl-thiopropylamine greater than S-adenosylethionine greater than S-inosylmethionine greater than S-adenosylhomocysteins. S-adenosyl-(2-hydroxy-4-methylthio)butyric acid exerted inhibition of a mixed type. S-insoyl-(2-hydroxy-4-methylthio)butyric acid, S-inosylhomocysteine, and S-ribosylhomocysteine were without effect. On the basis of the inhibition data, the methionine-amino, adenine-amino, and methyl groups were identified as group important in the binding of S-adenosylmethionine to the transport protein. Comparison is made with the specificities of various transmethylating enzymes utilizing S-adenosylmethionine. In addition, a number of conventional and temperature-sensitive S-adenosylmethionine transport mutants were isolated and analyzed in an attempt to identify the structural character of the specific transport protein(s). The data obtained suggest that only a single gene (a single polypeptide) is involved in specific S-adenosylmethionine transport. Apparent interallelic complementation supports the assumption that the functional form of the protein is composed of two or more copies of a monomer.


Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats.
Unilateral damage to sensorimotor cortical (SMC) regions can profoundly impair skilled reaching function in the contralesional forelimb. Such damage also results in impairments and compensatory changes in the less-affected/ipsilesional forelimb, but these effects remain poorly understood. Furthermore, anesthetization of the ipsilesional hand in humans with cerebral infarcts has been reported to produce transient functional improvements in the paretic hand [Floel A, Nagorsen U, Werhahn KJ, Ravindran S, Birbaumer N, Knecht S, et al. Influence of somatosensory input on motor function in patients with chronic stroke. Ann Neurol 2004;56:206-12; Voller B, Floel A, Werhahn KJ, Ravindran S, Wu CW, Cohen LG. Contralateral hand anesthesia transiently improves poststroke sensory deficits. Ann Neurol 2006;59:385-8]. One aim of this study was to sensitively assay the bilateral effects of unilateral ischemic SMC damage on performance of a unimanual skilled reaching task (the single pellet retrieval task) that rats had acquired pre-operatively with each forelimb. The second aim was to determine whether partially recovered contralesional reaching function is influenced by anesthetization of the ipsilesional forelimb. Unilateral SMC lesions were found to result in transient ipsilesional impairments in reaching success and significant ipsilesional abnormalities in reaching movements compared with sham-operates. There were major contralesional reaching impairments which improved during a 4 week training period, but movements remained significantly abnormal. Anesthetization of the ipsilesional forelimb with lidocaine at this time attenuated the contralesional movement abnormalities. These findings indicate that unilateral ischemic SMC lesions impair skilled reaching behavior in both forelimbs. Furthermore, after partial recovery in the contralesional forelimb, additional improvements can be induced by transient anesthetization of the ipsilesional forelimb. This is consistent with the effects of unilateral anesthetization in humans which have been attributed to the modulation of competitive interhemispheric interactions. The present findings suggest that such interactions are also likely to influence skilled reaching function in rats.


Insomnia, poor sleep quality and perinatal suicidal risk: A systematic review and meta-analysis.
Suicidal risk in mothers is a public health priority. Risk factors include biological, psychological and psychosocial factors. Among the biological factors, the role of sleep disturbances as potential contributors to increased suicidal risk during the peripartum period is becoming apparent. To explore this further, we conducted a systematic review following the PRISMA criteria. Currently, 10 studies have examined the role of insomnia and poor sleep quality in suicidal risk during the peripartum period and have involved 807,760 women. The data showed that disturbed sleep and poor sleep quality increase the risk of suicidal ideation in both pregnant women with and without perinatal depression. The results of the meta-analysis indicated that insomnia and poor sleep quality increase the odds of suicidal risk in pregnant women by more than threefold (OR = 3.47; 95% CI: 2.63-4.57). Specifically, the odds ratio (OR) for poor sleep quality was 3.72 (95% CI: 2.58-5.34; p < 0.001), and for insomnia symptoms, after taking into account perinatal depression, was 4.76 (95% CI: 1.83-12.34; p < 0.001). These findings emphasise the importance of assessing and addressing sleep disturbances during the peripartum period to mitigate their adverse effects on peripartum psychopathology and suicidal risk.


Assessment of Variations in Oxidative Stress in Newborns from Caesarian and Normal Delivery Based on Apgar Score.
Fetal distress seems to be strongly related to fetal hypoxia, which is known to cause derangement of the balance between pro-oxidant and anti-oxidant factors by depleting the antioxidant reserve and increasing oxidative stress. Reduced Apgar score signify the fetal distress in postpartum period. The current study explores the severity of oxidative stress and nitrosative stress markers along with the antioxidant status in the cord blood of the newborns with low Apgar score (Group 1), fairly low Apgar score (Group 2) and normal Apgar score (Group 3) in both categories born by Cesarean section (CS) and Normal delivery (ND). Cord blood was collected from eighty full terms, mature neonates of both sexes; forty born via ND and 40 delivered by CS. Apgar scores were recorded and they were grouped based on the different levels of the score. Methemoglobin (HbM), RBC glucose-6-phosphate dehydrogenase (G6PD), RBC reduced glutathione (GSH) were measured as markers of oxidative stress, whereas serum nitrate and nitrite levels were assayed as markers of nitrosative stress. The data obtained were analyzed for the level of significance between study variables. One way ANOVA revealed statistically significant difference between the means of HbM (1.48±0.52, 1.03±0.4 and 0.69±0.31 for Group 1, 2 and 3 respectively, p<0.001), RBC G6PD (15.62±1.99, 18.16±2.47, 21.93±3.91) RBC GSH (7.7±1.55, 10.75±2.31, 16±6.10), serum nitrate (63.18±17.14, 49.29±14.39, 40.86±8.83) serum nitrite (4.89±1.8, 4.64±1.04, 3.69±0.72) between the three groups of ND neonates. The results were almost similar in CS neonates (HbM - 2.17±0.95, 1.45±0.62, 0.8±0.3; G6PD - 12.54±2.31, 14.31±2.17, 18.1±3.13; GSH - 7.6±2.23, 9±2.11, 12.78±2.83) except serum nitrate and nitrite where no significant difference was found between means among the different Apgar groups. The results suggest that lowest Apgar score ND neonates are exposed to highest oxidative, nitrosative stress and have the poorest antioxidant defense. The CS neonates have the similar fate except the insignificant difference between the nitrosative stresses among the three Apgar score groups signifying that they are better protected against the nitrosative stress than their ND counterparts.


The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.
CD4 T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. The molecular basis of the differentiation of these cells from naive T cell precursors is, however, unclear. We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed at a high level in naive, freshly activated T cells and Th2 lineage cells, but subsides to a minimal level in Th1 lineage cells as naive cells commit to their Th subset. Antisense GATA-3 inhibited the expression of all Th2 cytokine genes in the Th2 clone D10. GATA-3 directly activated an IL-4 promoter-luciferase reporter gene in M12 cells. In transgenic mice, elevated GATA-3 in CD4 T cells caused Th2 cytokine gene expression in developing Th1 cells. Thus, GATA-3 is necessary and sufficient for Th2 cytokine gene expression.


Primary care trusts. Cut to the quick.
A change management programme set up by a primary care trust has resulted in most of its general practices offering patients appointments within 24 hours. A range of outreach clinics in general practices have increased outpatient capacity and achieved high attendance rates. All practices receive information on their referral rates. The PCT has used a private hospital for patients waiting more than 13 weeks for orthopaedic operations.


[Disease burden and prediction of oral cancer attributable to smoking in China from 1990 to 2019].
Objective: To analyze the trend of disease burden of oral cancer attributable to smoking in China from 1990 to 2019, and predict the mortality trend of oral cancer from 2020 to 2034, providing scientific basis for formulating targeted oral cancer prevention and treatment strategy to achieve the goal of "Healthy China 2030". Methods: Using partial data on the global burden of disease in China in 2019, attributive death and disability adjusted life year (DALY) were used to describe. The trend of changes in the burden of oral cancer disease attributed to smoking was analyzed by using the Joinpoint regression model to estimate the annual average percentage change (AAPC) of age standardized mortality and DALY rates. Meanwhile, the Bayesian age-period- cohort model is used to predict oral cancer deaths and DALY trends attributed to smoking over the next 15 years. Results: The age-standardized mortality rate and DALY rate in China from 1990 to 2019 showed an overall upward trend, with an average annual increase of 1.49% (95%CI: 1.34%-1.65%, P<0.001) and 1.41% (95%CI: 1.24%-1.59%, P<0.001) respectively, higher than around the earth and in regions with different socio-demographic index (SDI). In 2019, 46.74% (10 584/22 642) of oral cancer deaths in China were attributed to smoking. Compared to 1990, the number of attributed deaths in 2019 increased by 293.75% (7 896/2 688), while DALY increased by 257.97% (189 039/73 280). Moreover, the growth rates of attributed deaths and DALY in males [304.95% (7 584/2 487) and 265.60% (183 349/69 033), respectively] were significantly higher than those in females [154.73% (311/201) and 133.95% (5 690/4 248), respectively] (P<0.001). The age group results showed that the proportion of deaths and DALY gradually transitioned towards the elderly (>60 years old). The expected number of deaths would increase from 10 731 in 2020 to 14 125 in 2034, with a rise of 31.63% (3 394/10 731). Simultaneously, DALY would increase from 267 064 person years in 2020 to 326 634 person years in 2034, with a rise of 22.31% (59 570/267 064). Conclusions: From 1990 to 2019, the burden of oral cancer diseases attributed to smoking in China showed an increasing trend, with a higher growth rates than in the global and different SDI regions. There were differences in gender and age, and the burden of oral cancer diseases attributed to smoking in China would continue to increase in the next 15 years. It is necessary to educate on the adverse effects of tobacco consumption and to conduct vigilant oral self-examination among high-risk groups to help early detection and intervention at the same time.


[Simultaneous determination of the enantiomers of verapamil and norverapamil in plasma by high performance capillary electrophoresis].
An analytical method has been developed to determine simultaneously plasma concentration of the enantiomers of verapamil and its major metabolite, norverapamil, using capillary zone electrophoresis. Trimethyl-beta-cyclodextrin was selected as chiral selector. Good separation was achieved under the conditions as below: Running electrolyte was pH 2.5, 60 mmol.L-1 phosphate buffer containing 60 mmol.L-1 trimethyl-beta-cyclodextrin; capillary: 30 cm x 75 microns (ID), coated; setpoint of capillary temperature: 20 degrees C; detector: UV 200 nm; injection: electromigration at 12 kV for 7 s; running voltage: 14 kV. Solvent of sample was doubly deionized water. The migration times of enantiomers were less than 12 min. The good linear range was from 300.0 ng.ml-1 to 2.50 ng.ml-1. Relative standard deviations of assay accuracy and precision were less than 12%. It fits for routine therapeutic monitoring as it is highly efficient, rapid, sensitive, with less solvent and sample consumption and automation.


Review: The function of regulatory T cells at the ocular surface.
Regulatory T cells (Tregs) are critical modulators of immune homeostasis. Tregs maintain peripheral tolerance to self-antigens, thereby preventing autoimmune disease. Furthermore, Tregs suppress excessive immune responses deleterious to the host. Recent research has deepened our understanding of how Tregs function at the ocular surface. This manuscript describes the classification, the immunosuppressive mechanisms, and the phenotypic plasticity of Tregs. We review the contribution of Tregs to ocular surface autoimmune disease, as well as the function of Tregs in allergy and infection at the ocular surface. Finally, we review the role of Tregs in promoting allotolerance in corneal transplantation.


Lotus Seed Green Embryo Extract and a Purified Glycosyloxyflavone Constituent, Narcissoside, Activate TRPV1 Channels in Dorsal Root Ganglion Sensory Neurons.
Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbinis [PN]) green embryo extract. However, the specific bioactive components and associated molecular mechanisms remain largely unknown. This study aimed to identify the ion channel-activating mechanisms of PN extracts. Using fluorometric imaging and patch-clamp recordings, PN extracts were screened for calcium channel activation in dorsal root ganglion (DRG) neurons. The TRPV1 channels in DRG neurons were strongly activated by the PN extract (mean amplitude of 131 ± 45 pA at 200 μg/mL) and its purified glycosyloxyflavone narcissoside (401 ± 271 pA at 100 μM). Serial treatment with a 200 μg/mL PN extract in TRPV1-overexpressing HEK293T cells induced robust desensitization to 10 ± 10% of the initial current amplitude. Thus, we propose that the PN extract and narcissoside function as TRPV1 agonists. This new finding may advance our knowledge regarding the traditional and scientific functions of PN in human health and disease.


An accurate and stable nitrate-selective electrode for the in situ determination of nitrate in agricultural drainage waters.
A field evaluation of a novel nitrate-ion selective electrode (ISE) was undertaken by continuous immersion over a period of 5 months in agricultural drainage weirs. The nitrate sensor N,N,N-triallyl leucine betaine was covalently attached to polystyrene-block-polybutadiene-block-polystyrene (SBS) using a free radical initiated co-polymerisation, to produce a rubbery membrane which was incorporated into a commercially available electrode body. A measurement unit was constructed comprising the nitrate-ISEs, a reference electrode and a temperature probe connected through a pre-amplifier to a data-logger and battery supply. A temperature correction algorithm was developed to accomodate the temperature changes encountered in the drainage weirs. The nitrate results obtained with the ISEs at hourly intervals compared very favourably (R2 = 0.99) with those obtained with laboratory automated chemical determinations made on contemporaneous samples of drainage in a concentration range 0.47-16 ppm nitrate-N. The ISEs did not require re-calibration and no deterioration in performance or fouling of the membrane surface was observed over four months of deployment.


Non-invasive Neurophysiology in Learning and Training: Mechanisms and a SWOT Analysis.
Although many scholars deem non-invasive measures of neurophysiology to have promise in assessing learning, these measures are currently not widely applied, neither in educational settings nor in training. How can non-invasive neurophysiology provide insight into learning and how should research on this topic move forward to ensure valid applications? The current article addresses these questions by discussing the mechanisms underlying neurophysiological changes during learning followed by a SWOT (strengths, weaknesses, opportunities, and threats) analysis of non-invasive neurophysiology in learning and training. This type of analysis can provide a structured examination of factors relevant to the current state and future of a field. The findings of the SWOT analysis indicate that the field of neurophysiology in learning and training is developing rapidly. By leveraging the opportunities of neurophysiology in learning and training (while bearing in mind weaknesses, threats, and strengths) the field can move forward in promising directions. Suggestions for opportunities for future work are provided to ensure valid and effective application of non-invasive neurophysiology in a wide range of learning and training settings.


Social Structure, Social Learning, and the Severity of Physical Intimate Partner Violence Against Women in Nigeria.
Using the Nigerian Demographic and Health Survey (NDHS) of 2013, this study applies the social structure (feminist) and social learning perspective in understanding the severity of physical intimate partner violence (IPV) in Nigeria. About 26,403 married women were analyzed from the 2013 NDHS data. Multinomial regression was used to analyze variables that capture the social structural and social learning perspectives in relation to women's experience of minor and severe physical IPV. The study revealed that primary and secondary educational attainment, and being employed predicted severe physical IPV victimization. Alcohol consumption by the respondents' spouses, being a victim of childhood abuse, and witnessing IPV between parents predicted severe physical IPV. The finding of this study implies that experiences of IPV take place within a sociocultural context that shapes the social realities of the average Nigerian woman.


[Renal-cell adenocarcinoma and massive retroperitoneal hemorrhage during pregnancy].
We report a case of renal cell carcinoma that had manifested as massive retroperitoneal hemorrhage in the second trimester of pregnancy. The diagnosis was made on the basis of the clinical and ultrasound findings. The patient was submitted to unilateral nephrectomy at 27 wk of gestation and she delivered by cesarean section at 35 wk gestation. Both mother and infant are well 1 year postoperatively.


A Case of Idiopathic Dense Vitreous Hemorrhage: Suspected Rupture of a Large Retinal Arterial Macroaneurysm on the Optic Disc.
We report a novel case of vitreous hemorrhage associated with suspected rupture of 2-disc-diameter retinal arterial macroaneurysm on the optic disc. A 90-year-old woman presented with blurred vision (sudden onset) in her left eye. Examination of the fundus revealed acute onset vitreous hemorrhage of unknown origin without retinal detachment. She underwent vitrectomy, but after excision of the dense vitreous hemorrhage, a 2-disc-diameter hematoma appeared on the optic disc and was removed promptly. Because the bleeding at the base of the hematoma was of arterial origin and pulsating, the first vitrectomy could not achieve hemostasis. Five days after the first surgery, we performed a second vitrectomy. This revealed a subretinal hemorrhage along the superior and inferior arcade vessels and a macular hole, which was almost completely closed with an inverted internal limiting membrane flap. Unfortunately, the macular hole reopened 41 days after the second surgery. In patients presenting with only a large hematoma on the optic disc, it might be prudent to leave the hematoma. However, this large retinal arterial macroaneurysm was on a rare location on the optic disc, making it doubly difficult for the surgeons to diagnose and choose the best option intraoperatively. The differential diagnosis for dense vitreous hemorrhage of unknown origin should include a large retinal arterial macroaneurysm on the optic disc.


A Review of Current Treatment Options for Coccygodynia.
Coccygodynia is pain within the coccyx area. The diagnosis is made clinically with symptoms of pain in the coccyx region and worsening pain in sitting position. The initial treatment is conservative therapy. For patients who do not respond to conservative therapies, there are further interventions available. This includes local injection of local anesthetics and steroids, neurolysis of sacral nerve roots, caudal epidural block, pulse radiofrequency (PRF), intra-rectal massage and manipulation, ganglion impar block, levator ani massage and stretching, coccyx manipulation, and coccygectomy. The purpose of this review is to evaluate the efficacies of these interventions in the treatment of coccygodynia. Literature search was performed with the keywords including coccygodynia, treatment, and coccygectomy, on PubMed and Google Scholar between August 2012 and August 2017. Thirteen studies with patients age 18 and over who underwent treatments for coccygodynia were selected for analysis. These treatments include conservative therapies (physical therapy and capsaicin patch), interventional techniques (local injections with steroids and local anesthetic, pulsed radiofrequency ablation of ganglion impar, extracorporeal shock wave therapy), and surgical techniques (complete and partial coccygectomies). The results from these studies demonstrated that most patients had significant pain relief with these techniques. Our literature review demonstrated various interventions including coccygectomy can be effective in the treatment of coccygodynia refractory to conservative therapies. There is a growing body of clinical evidence to support that coccygectomy is an effective treatment for patients with debilitating pain who had failed interventional therapies. Further randomized control studies should be conducted to examine duration of pain relief after coccygectomy and associated surgical complications.


Myoglobin does not predict local toxicity in isolated limb perfusion.
Isolated limb perfusion (ILP) is a treatment option for patients with in-transit metastases of malignant melanoma in the extremities, as well as locally advanced sarcoma. ILP allows for a delivery of high-dose chemotherapy to an isolated extremity with minimal systemic toxicity. However, local toxicity like oedema, blistering, nerve damage and compartment syndrome can occur. Myoglobin measurements have been used as a screening method to predict the most severe cases of local toxicity. The aim was to investigate if myoglobin is a predictive factor for local toxicity after ILP in patients with melanoma in-transit metastases. One hundred and ninety-three patients were treated for the first time with ILP for in-transit metastases between 2001 and 2015. Myoglobin was measured once the first hours after the perfusion (POD0), and for the first five post-operative days (POD1-5). Local toxicity was graded according to Wieberdink, and grouped in mild (I and II), moderate (III), and severe (IV and V). Wieberdink-groups were compared with myoglobin measurements, and myoglobin measurements were compared between gender, perfusion time, perfusion temperature and cannulated vessels. There is no statistically significant difference in myoglobin serum levels during the first five days post perfusion between patients suffering from mild, moderate or severe local toxicity. There is no difference between toxicity groups when it comes to distribution of sex, tumour size, or tumour numbers. Levels of myoglobin do not predict local toxicity for patients with melanoma in-transit metastases treated with ILP when measured during the first five post-operative days.


Struggle between survival and death: the life experience of Taiwanese older adults with suicidal ideation.
The purpose of this study was to use grounded theory to explore the subjective experiences of suicidal ideation among Taiwanese older adults in the community. Fifteen participants ages 66 to 88 were interviewed, and data were analyzed using a constant comparative analysis method. The Struggle Between Survival and Death was defined as the core category. Loss of loved ones, possession, and health was defined as the antecedent condition. The older adults struggled between survival and death during a suicidal ideation process categorized as negative emotions without an outlet, reminiscence about past achievements,lingering or persistent suicidal ideation, and hesitation to commit suicide. Lastly, the participants reported experiencing a meaningless existence in their daily lives. It is crucial to provide sensitive support to older adults who have had loss of life experiences, including providing an outlet to express negative emotions, religious support, reminiscence therapy, or a life review.


Effect of dehydroaltenusin-C12 derivative, a selective DNA polymerase alpha inhibitor, on DNA replication in cultured cells.
Dehydroaltenusin is a selective inhibitor of mammalian DNA polymerase alpha (pol alpha) from a fungus (Alternaria tennuis). We have designed, synthesized, and characterized a derivative of dehydroaltenusin conjugated with a C12-alkyl side chain (dehydroaltenusin-C12 [C12]). C12 was the strongest pol alpha inhibitor in vitro. We introduced C12 into NIH3T3 cells with the help of a hypotonic shift, that is, a transient exposure of cultured cells in hypotonic buffer with small molecules which can not penetrate cells. The cells that took in C12 by hypotonic shift showed cell growth inhibition. At a low concentration (5 microM), DNA replication was inhibited and several large replication protein A (RPA) foci, which is different from dUTP foci. Furthermore, when C12 was incubated with aphidicolin, RPA foci were not observed in cells. Finally, these findings suggest that C12 inhibited DNA replication through pol alpha inhibition, and generated single-stranded DNA, resulted in uncoupling of the leading strand and lagging strand synthesis. These findings suggest that C12 could be more interesting as a molecule probe or anticancer agent than aphidicolin. C12 might provide novel markers for the development of antiproliferative drugs.


Atomic force and scanning electron microscopy of atmospheric particles.
Atomic force microscopy (AFM) and scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) have been used for both morphological and elemental mass analysis study of atmospheric particles. As part of the geometrical particle analysis, and in addition to the traditional height profile measurement of individual particles, AFM was used to measure the volume relative to the projection area for each particle separately, providing a particle shape model. The element identification was done by the EDS analysis, and the element mass content was calculated based on laboratory calibration with particles of known composition. The SEM-EDS mass measurements from two samples collected at 150 and 500 m above the surface of the Mediterranean Sea were found to be similar to mass calculations derived from the AFM volume measurements. The AFM results show that the volume of most of the aerosols that were identified as soluble marine sulfate and nitrate aerosol particles can be better estimated using cylindrical shapes than spherical or conical geometry.


Massive Lumbosacral Subcutaneous Exudate After Surgical Treatment of a Large Lipomyelocele: Case Report and Literature Review.
Lipomyelocele is an uncommon type of lipoma that occurs with spina bifida. We present the clinical course and therapeutic process of a female who underwent resection of a lipomyelocele and developed a massive lumbosacral subcutaneous exudate postoperatively. The therapeutic process is described in detail, and a review of the relevant literature on lipomyelocele is presented. A 23-year-old woman presented to our institution complaining of a large lumbosacral subcutaneous mass. She underwent surgical resection of the mass and untethering of the spinal cord under intraoperative neurophysiologic monitoring. A massive lumbosacral subcutaneous exudate developed postoperatively. After excluding cerebrospinal fluid (CSF) leakage, we placed a suction drain. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor of this journal. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. Postoperative pathologic examination confirmed the diagnosis of lipomyelocele. Continuation of the negative-pressure drain for 1 week yielded >1000 mL of fluid. The patient recovered well and developed no further subcutaneous exudate. In a patient with massive lumbosacral subcutaneous exudate after surgical treatment of a large lipomyelocele, continuous negative-pressure drainage can be an effective treatment method after excluding CSF leakage.


Cystic Formation After Stereotactic Radiosurgery of Brain Metastasis.
Limited information is available on the natural history and etiology of cystic formation after stereotactic radiosurgery (SRS) for brain metastases (BM). We aimed to characterize the natural history of cyst formation after SRS of BM and analyze potential risk factors. We retrospectively reviewed 214 consecutive patients who underwent a total of 1106 SRSs for BM. Demographic, clinical, dosimetric, and magnetic resonance imaging MRI data were reviewed. Statistical analysis was accomplished using Student's t test, and univariate and multivariate logistic regression. The median patient age was 61 years (range, 19-91 years), and the median duration of follow-up was 424 days (range, 91-2934 days). Eleven cases of cyst formation (0.9% of 1106 treated lesions) were identified at SRS-treated BM sites among 9 patients (2 patients developed cysts at independent sites). The median interval between first SRS and first evidence of cyst was 218 days. Seven of the 9 patients (78%) sustained progressive cyst expansion and neurologic decline requiring steroid treatment. Four of these 7 patients (57%) experienced continued neurologic decline and needed surgical fenestration. On univariate analysis, receipt of >4 rounds of SRS was the sole variable associated with an increased risk of cyst formation (odds ratio, 16.58; P = 0.001). This association remained robust after adjusting for duration of follow-up (odds ratio, 13.59; P = 0.003). In our experience with 1106 SRS-treated cases of BM, cyst formation was a rare phenomenon. However, 1 in 3 patients who underwent >4 rounds of SRS sustained cyst formation. A high proportion (78%) of SRS-associated cysts progressively expanded and required medical or surgical treatment.