LncRNA-LINC00472 suppresses the malignant progression of non-small cell lung cancer via modulation of the miRNA-1275/Homeobox A2 axis.
Long non-coding RNAs (lncRNAs) are increasingly observed as regulatory factors for the initiation and progression of varying kinds of cancers. However, studies on lncRNAs in non-small cell lung cancer (NSCLC) progression are currently lacking. We intended to determine the role of lncRNA LINC00472 and its downstream regulatory mechanism in NSCLC, thus providing novel ideas for targeted therapies for NSCLC. The target signaling axis comprising the lncRNA/microRNA/mRNA was identified through bioinformatics analysis. Subcellular localization of LINC00472 was assessed with fluorescence in situ hybridization (FISH). Cellular function experiments were conducted to examine the proliferation, migration, invasion, and apoptosis of NSCLC cells, and dual-luciferase and RNA binding protein immunoprecipitation assays were performed to validate the binding relationship. Quantitative real-time polymerase chain reaction (qPCR) and western blot were utilized to assess the expression levels of the investigated gene and protein, respectively. The LINC00472 expression was markedly decreased in NSCLC tissues and cells. The FISH, combined with nuclear-cytoplasm separation assay, demonstrated that LINC00472 was mainly located in the cytoplasm. The overexpression of LINC00472 restrained proliferation and metastasis of NSCLC in vitro. The LINC00472 could target and repress miR-1275 level, and overexpression of LINC00472 reduced the miR-1275-dependent malignant cell phenotype in NSCLC. Further study revealed that HOXA2 was a downstream target of miR-1275 and was negatively modulated by miR-1275. Rescue assays exhibited that the overexpression of miR-1275 or inhibition of HOXA2 reversed the impact of LINC00472 overexpression on the malignant progression of NSCLC cells. The LINC00472 repressed the epithelial-mesenchymal transition (EMT) of NSCLC cells through miR-1275/HOXA2. The LINC00472 functioned as a competing endogenous RNA to modulate HOXA2 level by sponging miR-1275 in NSCLC. Simultaneously, the LINC00472/miR-1275/HOXA2 axis may be a possible therapeutic target and biomarker for NSCLC.


Wharton's jelly absence: a possible cause of stillbirth.
The umbilical cord is a structure that provides vascular flow between the fetus and the placenta. It contains two arteries and one vein, which are surrounded and supported by gelatinous tissue known as Wharton's jelly. There are many umbilical cord abnormalities that are related to the prognosis of fetus survival and birth weight. The authors report a case of umbilical cord constriction due to the localized absence of Wharton's jelly, which was undiagnosed antenatally and had a fatal outcome. A review of the association between the absence of Wharton's jelly and an unfavorable pregnancy outcome was undertaken.


A regulatory role for the redox status of the pepino mosaic virus coat protein.
Cysteine oxidations play important regulatory roles during animal virus infections. Despite the importance of redox modifications during plant infections, no plant virus protein has yet been shown to be regulated by cysteine oxidation. The potexvirus pepino mosaic virus (PepMV) is pandemic in tomato crops. Previously we modeled the structure of the PepMV particle and coat protein (CP) by cryo-electron microscopy and identified critical residues of the CP RNA-binding pocket that interact with the viral RNA during particle formation and viral cell-to-cell movement. The PepMV CP has a single cysteine residue (Cys127) central to its RNA binding pocket, which is highly conserved. Here we show that the Cys127Ser replacement diminishes PepMV fitness, and that PepMV CPWT is oxidized in vivo while CPC127S is not. We also show that Cys127 gets spontaneously glutathionylated in vitro, and that S-glutathionylation blocks in vitro the formation of virion-like particles (VLPs). VLPs longer than 200 nm could be formed after in planta CPC127S overexpression, while very short and dispersed VLPs were observed after CPWT overexpression. Our results strongly suggest that the CP redox status regulates CP functions via cysteine oxidation.


A scoping review of portable sensing for out-of-lab anterior cruciate ligament injury prevention and rehabilitation.
Anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) surgery are common. Laboratory-based biomechanical assessment can evaluate ACL injury risk and rehabilitation progress after ACLR; however, lab-based measurements are expensive and inaccessible to most people. Portable sensors such as wearables and cameras can be deployed during sporting activities, in clinics, and in patient homes. Although many portable sensing approaches have demonstrated promising results during various assessments related to ACL injury, they have not yet been widely adopted as tools for out-of-lab assessment. The purpose of this review is to summarize research on out-of-lab portable sensing applied to ACL and ACLR and offer our perspectives on new opportunities for future research and development. We identified 49 original research articles on out-of-lab ACL-related assessment; the most common sensing modalities were inertial measurement units, depth cameras, and RGB cameras. The studies combined portable sensors with direct feature extraction, physics-based modeling, or machine learning to estimate a range of biomechanical parameters (e.g., knee kinematics and kinetics) during jump-landing tasks, cutting, squats, and gait. Many of the reviewed studies depict proof-of-concept methods for potential future clinical applications including ACL injury risk screening, injury prevention training, and rehabilitation assessment. By synthesizing these results, we describe important opportunities that exist for clinical validation of existing approaches, using sophisticated modeling techniques, standardization of data collection, and creation of large benchmark datasets. If successful, these advances will enable widespread use of portable-sensing approaches to identify ACL injury risk factors, mitigate high-risk movements prior to injury, and optimize rehabilitation paradigms.


Nutritional and behavioral determinants of adolescent obesity: a case-control study in Sri Lanka.
Global prevalence of adolescent obesity is rising at an alarming rate leading to increase risk of adult obesity. Obesity in adolescence is postulated to have a significant impact on both physical and psychological health of an individual. The study aim was to identify nutritional and behavioral risk factors associated with obesity among adolescent Sri Lankan school girls. In this case-control study, age and ethnicity matched 100 cases (BMI-for-age above +2SD) and 100 controls (BMI-for-age between -2SD to +1 SD) adolescent girls between 14 to 18 years of age were recruited. Predicted risk factors of obesity were assessed through an interviewer administrated questionnaire. A three day diet diary and long version of international physical activity questionnaire were used to assess daily energy intake and energy expenditure from physical activity, respectively. The significant differences in mean values were evaluated using paired t-test. Multivariable logistic regression analysis was performed to assess the risk factors associated with obesity. Obese girls had significantly higher BMI (31.3, 20.2 kgm-2 p < 0.0001), waist circumference (90.8, 68.2 cm p < 0.0001), energy intake (2235.4, 1921.7 kcal p < 0.0001) and lower energy expenditure from physical activity (894.6, 1844.3 MET (metabolic equivalent)-min/week p < 0.0001). High family income (Odds ratio [OR], 2.99, 95% confidence interval [CI] 1.13-7.88), first born in family (2.73, 1.25-5.97), skipping breakfast (3.99, 1.81-8.80), consumption of fruits < 4 days per week (2.18, 1.02-4.67), screen viewing > 2 hours/ day (2.96, 1.33-6.61), energy intake (3.97, 3.19-16.36), significantly increased the risk of obesity, whereas increased physical activity (4.34, 1.33-14.14) decreased the risk. Irregular menstruation (4.34, 1.33-14.14) was noted among the obese. Socioeconomic and behavior factors are major determinants of adolescent obesity in Sri Lanka. There is an urgent need to implement awareness as well as behavior modification programmes targeting adolescents, parents and schools to control childhood and adolescent obesity.


Competency to stand trial and the seriousness of the charge.
Authorities disagree as to whether and how the mental capacity required for competence to stand trial should change as the charges against a defendant become more serious. Intuition and practice in other areas of law and psychiatry suggest that the mental capacity required should increase in these circumstances. The reasons relate to our belief that serious mistakes are more to be avoided and to a principle of "proportionality," according to which the threshold level of capacity required is derived, in part, from the consequences of a person's being found competent. The article compares two approaches to "proportionality." The conclusions have implications for the wording of examiners' conclusions and for the criteria by which patients are regarded as "restored to competence."


One-step synthesis of an organic-inorganic hybrid boronate affinity monolithic column with synergistic co-monomers.
An organic-inorganic hybrid and synergistic boronate affinity (BA) monolithic column was synthesized by a novel "one-step" approach. We report on the synthesis of a unique organic-inorganic hybrid affinity monolith by using TEOS, the organic silane, N-(β-aminoethyl)-γ-aminopropyltriethoxysilane (AEAPTES) and γ-MAPS as the co-precursors, 4-vinylphenylboronic acid as the functionalized monomer, and azobisisobutyronitrile (AIBN) as the initiator. Due to the presence of amino groups in the AEAPTES molecule, the prepared monolith exhibits several attractive properties. The monolith will be more hydrophilic and can bind with cis-diol compounds at neutral pH by a mechanism of intermolecular B-N coordination. The resulting hybrid boronate affinity monoliths have potential applications in specific recognition and enrichment of cis-diol biomolecules under neutral conditions.


Mesoporous polyhedral cages and shells formed by textured self-assembly of ZnO nanocrystals.
We report a new structure, mesoporous structured polyhedral drum and spherical cages and shells formed by textured self-assembly of ZnO nanocrystals, which are made by a novel self-assembly process during epitaxial surface oxidation. The cages/shells exhibit unique geometrical shapes, and their walls are composed of mesoporous and textured ZnO nanocrystals. The structures of the cages and shells are studied, and a growth mechanism is proposed to be a process following solidification of the Zn liquid droplets, surface oxidation, and sublimation.


Physical Health and Dual Diagnosis.
The physical health of people with mental illness may be neglected for a variety of reasons. This paper looks at the common physical health problems experienced by people with a dual diagnosis of substance misuse and serious mental illness, and suggests ways of assessing and managing them.


Comparison of enalapril and conventional vasodilator therapy in patients with chronic congestive heart failure.
The aim of this study was to investigate the role of the renin-angiotensin-aldosterone system during anti-heart failure treatment with additional enalapril versus conventional vasodilator therapy (hydralazine + sorbitrate) and to assess whether or not enalapril can be suggested as the preferential vasodilator therapy in patients with chronic congestive heart failure. Over a 2.5-year period, 120 patients (New York Heart Association II-IV, creatinine less than or equal to 2.0 mg/dl) were enrolled in the study and randomly assigned to receive enalapril or hydralazine and sorbitrate therapy in addition to optimal digitalis and diuretics administration. At the end of a one-year followup, there was a tendency for mortality to be lower in the enalapril[correction of enlapril] group (4 cases) compared to the conventional group (9 cases), but the difference was not significant (p = 0.21). Both groups showed similar increases in plasma renin activity. The plasma aldosterone level decreased significantly in the enalapril group (p less than 0.005); whereas it rose significantly in the conventional group (p less than 0.005). The plasma norepinephrine level of the enalapril group fell significantly when compared with the conventional group. Thus, enalapril therapy achieved better reduction in the activating sympathetic system (p less than 0.0001). Reduction in the anti-diuretic hormone level was also found to be highly significant in the enalapril group, whereas no difference was seen in the conventional group. Furthermore, the serum creatinine level and blood urea nitrogen remained unchanged in the conventional group; whereas both were demonstrated to be reduced significantly in the enalapril group at a 1-year follow up.(ABSTRACT TRUNCATED AT 250 WORDS)


Survival analysis of adult tuberculosis disease.
We conducted a survival analysis of all the confirmed cases of Adult Tuberculosis (TB) patients treated in Cork-City, Ireland. The aim of this study was to estimate Survival time (ST), including median time of survival and to assess the association and impact of covariates (TB risk factors) to event status and ST. The outcome of the survival analysis is reported in this paper. We used a retrospective cohort study research design to review data of 647 bacteriologically confirmed TB patients from the medical record of two teaching hospitals. Mean age 49 years (Range 18-112). We collected information on potential risk factors of all confirmed cases of TB treated between 2008-2012. For the survival analysis, the outcome of interest was 'treatment failure' or 'death' (whichever came first). A univariate descriptive statistics analysis was conducted using a non- parametric procedure, Kaplan -Meier (KM) method to estimate overall survival (OS), while the Cox proportional hazard model was used for the multivariate analysis to determine possible association of predictor variables and to obtain adjusted hazard ratio. P value was set at <0.05, log likelihood ratio test at >0.10. Data were analysed using SPSS version 15.0. There was no significant difference in the survival curves of male and female patients. (Log rank statistic = 0.194, df = 1, p = 0.66) and among different age group (Log rank statistic = 1.337, df = 3, p = 0.72). The mean overall survival (OS) was 209 days (95%CI: 92-346) while the median was 51 days (95% CI: 35.7-66). The mean ST for women was 385 days (95%CI: 76.6-694) and for men was 69 days (95%CI: 48.8-88.5). Multivariate Cox regression showed that patient who had history of drug misuse had 2.2 times hazard than those who do not have drug misuse. Smokers and alcohol drinkers had hazard of 1.8 while patients born in country of high endemicity (BICHE) had hazard of 6.3 and HIV co-infection hazard was 1.2. There was no significant difference in survival curves of male and female and among age group. Women had a higher ST compared to men. But men had a higher hazard rate compared to women. Anti-TNF, immunosuppressive medication and diabetes were found to be associated with longer ST, while alcohol, smoking, RICHE, BICHE was associated with shorter ST.


An International Survey of Allogeneic Hematopoietic Cell Transplantation for X-Linked Agammaglobulinemia.
X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by variants in Bruton's tyrosine kinase (BTK). XLA patients require lifelong immunoglobulin replacement therapy (IgRT). Only few XLA patients are indicated for allogeneic hematopoietic cell transplantation (HCT) because of severe complications. Accordingly, the published transplantation experience in XLA is minimal. We aimed to collect clinical data of XLA patients who received HCT in an international framework and to establish appropriate transplantation criteria and methods for XLA patients. XLA patients were recruited through a questionnaire and a literature review. The data are on patient characteristics and transplantation methods and outcomes. In this study, twenty-two XLA patients who underwent HCT were recruited. The indication for HCT was recurrent or life-threatening infection in sixteen patients, malignancy in three, and other factors in three. A myeloablative conditioning, reduced toxicity myeloablative conditioning (RT-MAC), and reduced intensity conditioning (RIC) were selected in four, ten, and eight patients, respectively. Engraftment was achieved in 21 patients (95%). In all patients, 2-year overall survival (OS) and event-free survival (EFS) were 86% and 77%, respectively. In patients who received RT-MAC or RIC using treosulfan, busulfan, or melphalan, 2-year OS and EFS were 82% and 71%, respectively. Finally, twenty-one patients (95%) obtained complete or stable high-level mixed chimerism (50-95%), and the 1-year discontinuation rate of IgRT was 89%. Based on the concept in which IgRT is the standard treatment for XLA, HCT may be an effective and safe alternative treatment option for XLA patients, and IgRT can be discontinued following transplantation. It is ideal to perform HCT in XLA patients for whom transplantation is indicated before they develop organ damage.


Action of testosterone in melanin metabolism in liver of toad (Bufo melanostictus).
The melanin content of liver of male toad was altered by testosterone injection. A single injection of testosterone at a dose of 1 microgram/g or 2 microgram/g of body weight caused an increase in melanin content of liver of male toad on the 3rd and 5th day after injection. With lower doses (0.1 microgram/g and 0.5 microgram/g), however, there was no alteration of melanin content of liver. Compared to the results obtained with 1 microgram of testosterone per g of body weight, the degree of response with respect to the melanin content with 2 microgram/g tended to be higher, but the difference was not statistically significant. The female toads remained unaffected with respect to melanin content of liver with these doses of testosterone used.


[An Analysis of the Controversy on the Psychoprophylaxis Method in the Japanese Medical Journal "Obstetrics and Gynecology," 1954-1957].
The methods of painless childbirth are generally divided into two kinds: "with drugs" and "without drugs." In Japan, the full-scale initiation of these two types of painless childbirth methods in clinical practice started in the early 1950s. The practice of the psychoprophylaxis method (PPM)--one of the painless childbirth methods "without drugs"--started in 1953. Japanese obstetricians had discussed the practicability of PPM for painless childbirth and had doubted the scientific nature and originality of PPM as a viable method. Therefore, they published a series of articles in the Japanese medical journal "Obstetrics and Gynecology" from 1954 to 1957. Two representative obstetricians developed this controversy. Naotaro KUJI, the director of the Central Maternity Hospital of the Japanese Red Cross Society and the chief practitioner of PPM, emphasized that PPM was a more practical method, considering the Japanese medical legal situation where midwives were prohibited to use drugs. On the other hand, Kakuichi ANDO, the chief professor of the Department of Obstetrics and Gynecology of Keio University and the team leader of the practitioners of painless childbirth "with drugs," doubted the practicability of PPM. In the course of these discussions, both groups of obstetricians gradually came to a consensus to use the concept of "pain relief" in labor, instead of "painless" childbirth. They also agreed to adopt methods "with drugs" and "without drugs," including PPM, according to the presented case.


Familial silver staining patterns of human nucleolus organizer regions (NORs).
The silver staining patterns of the nucleolus organizer regions (NORs), an indication of rDNA transcriptional activity, were studied in metaphases from lymphocyte cultures of 20 karyotypically normal members of three families selected for a large sibling number or a monozygotic twin pair. Quinacrine polymorphic markers and bands were used to identify the acrocentrics and to determine their parental origin. A comparison of the silver staining frequencies among siblings and between parent and child indicated no significant differences for any acrocentric in the twin pairs and significant differences (P less than .05) for only one of the 20 acrocentrics segregating in each of two families. These two acrocentrics had short stalks with very small silver deposits (AgNORs). The mean size of the AgNOR, based on a relative score, was not significantly different (P greater than .05) for each homolog between the twin pair and in approximately 70% of the acrocentrics shared by members of the one family analyzed. The frequency with which a particular chromosome was silver stained demonstrated a significant correlation (r2 = .732) with the size of AgNOR. There was a close correlation (r2 = .609) between stalk length and the size of the AgNOR. We conclude that the frequency of silver staining and the mean size of the AgNOR are characteristics inherent in a particular chromosome carried from one generation to the next.


The middle ear in cleft palate children pre and post palatal closure.
A multicentre prospective trial was commenced in July 1984 to establish the incidence of otitis media with effusion (OME) in children born with a cleft of the palate. Additionally, the data recorded would allow an assessment of the effect of palatal closure on middle ear function. Prior to palatal closure, 97% of ears in a group of 50 patients had otitis media with effusion (OME). The insertion of a long-term ventilation tube provided a means of aeration of one ear with the non-ventilated ear acting as a control. Eighty percent of control ears had persistent OME during a 24-month follow-up period post palatal repair. It would seem that OME is universally present in children with a cleft palate prior to 4 months of age and this incidence is only marginally diminished by palatal surgery. The liaison between plastic surgical and ENT units should be even closer than before in order to manage these patients satisfactorily.


BoSCC: Bag of Spatial Context Correlations for Spatially Enhanced 3D Shape Representation.
Highly discriminative 3D shape representations can be formed by encoding the spatial relationship among virtual words into the Bag of Words (BoW) method. To achieve this challenging task, several unresolved issues in the encoding procedure must be overcome for 3D shapes, including: 1) arbitrary mesh resolution; 2) irregular vertex topology; 3) orientation ambiguity on the 3D surface; and 4) invariance to rigid and non-rigid shape transformations. In this paper, a novel spatially enhanced 3D shape representation called bag of spatial context correlations (BoSCCs) is proposed to address all these issues. Adopting a novel local perspective, BoSCC is able to describe a 3D shape by an occurrence frequency histogram of spatial context correlation patterns, which makes BoSCC become more compact and discriminative than previous global perspective-based methods. Specifically, the spatial context correlation is proposed to simultaneously encode the geometric and spatial information of a 3D local region by the correlation among spatial contexts of vertices in that region, which effectively resolves the aforementioned issues. The spatial context of each vertex is modeled by Markov chains in a multi-scale manner, which thoroughly captures the spatial relationship by the transition probabilities of intra-virtual words and the ones of inter-virtual words. The high discriminability and compactness of BoSCC are effective for classification and retrieval, especially in the scenarios of limited samples and partial shape retrieval. Experimental results show that BoSCC outperforms the state-of-the-art spatially enhanced BoW methods in three common applications: global shape retrieval, shape classification, and partial shape retrieval.


Fluorescence and SERS Imaging for the Simultaneous Absolute Quantification of Multiple miRNAs in Living Cells.
The simultaneous imaging and quantification of multiple intracellular microRNAs (miRNAs) are particularly desirable for the early diagnosis of cancers. However, simultaneous direct imaging with absolute quantification of multiple intracellular RNAs remains a great challenge, particularly for miRNAs, which have significantly different expression levels in living cells. We designed dual-signal switchable (DSS) nanoprobes using the fluorescence-Raman signal switch. The intracellular uptake and dynamic behaviors of the probe are monitored by its fluorescence signal. Meanwhile, real-time quantitative detection of multiple miRNAs is made possible by measurements of the surface-enhanced Raman spectroscopy (SERS) ratios. Moreover, the signal 1:n ratio amplification mode only responds to low-abundance miRNA (asymmetric signal amplification mode) for simultaneous visualization and quantitative detection of significantly different levels of miRNAs in living cells. miR-21 and miR-203 were successfully detected in living MCF-7 cells, in agreement with in vitro results from the same batch of cell lysates. The reported dual-spectrum imaging method promises to offer a new strategy for the intracellular imaging and detection of various types of biomolecules.


Covariance Between Parent and Child Symptoms Before and During the COVID-19 Pandemic.
COVID-19 has had unprecedented effects on American families, including increases in depression, anxiety, and irritability for both parents and children. While parents and children influence each other's psychological functioning during non-disaster times, this effect may be amplified during times of disaster. The current study investigated how COVID-19 influenced covariance of depressive symptoms and irritability in children and their parents. Three hundred and ninety-one parents and their 8- to 17-year-old children (Mage = 10.68 years old, 70% male, 86% White) from a large sample of children and parents, primarily from Southeastern Louisiana, completed self-report measures of depression and irritability approximately 6 weeks into the COVID-19 pandemic, as well as providing retrospective reports of their symptoms prior to the pandemic. Actor-partner interdependence models were used to measure the reciprocal effects of parent symptoms on children and vice versa, both before and during the pandemic. Actor effects in both the depressive symptoms and irritability models suggested that pre-COVID-19 depressive symptoms and irritability were robust predictors of early-COVID-19 depressive symptoms and irritability for both parents and children. Partner effects were also detected in the irritability model, in that parental irritability prior to COVID-19 was associated with decreased child irritability during the pandemic. Both before and during the pandemic, associations between parent and child depressive symptoms and irritability scores were weaker in families evidencing greater dysfunction. Results suggest that COVID-19-related stress is associated with increases in both parent and child symptomatology, and that family relationships likely influence associations between these symptoms.


Surgical venous thromboembolism prophylaxis: clinical practice update.
Perioperative medicine continues to evolve as new literature emerges. This article provides an update on prevention of venous thromboembolism (VTE) in surgical patients. We reviewed articles on VTE prevention in surgical patients published in peer-reviewed journals since the publication of 2012 ACCP guidelines on VTE prevention in surgical patients. Methods of VTE prophylaxis include aggressive ambulation, mechanical prophylaxis, and pharmacological prophylaxis. In non-orthopedic surgery, the overall approach remains assessment of thrombosis risk with the recommendation to use a risk assessment tool such as the modified Caprini score. Low molecular weight heparin (LMWH) appears to be more effective than unfractionated heparin (UFH) for VTE prophylaxis in non-orthopedic surgery. For orthopedic surgery, recent studies now recognize aspirin as an option for VTE prophylaxis after total hip arthroplasty, total knee arthroplasty, and hip fracture surgery. Extended prophylaxis with LMWH reduces the risk of symptomatic VTE in high risk abdominal and pelvic cancer surgery without an appreciable increase in risk of bleeding and decreased symptomatic VTE in major orthopedic surgery but with more minor but not major bleeding. Prophylactic Inferior vena cava (IVC) filter placement or surveillance compression ultrasonography is not recommended in management or detection of VTE in surgical patients. This article aims to provide insight into data from last several years which has potential to change clinical practices in perioperative setting.


Syntrophic propionate degradation response to temperature decrease and microbial community shift in an UASB reactor.
Propionate is an important intermediate product during the methane fermentation of organic matter, and its degradation is crucial for maintaining the performance of an anaerobic digester. In order to understand the effect of temperature on propionate degradation, an upflow anaerobic sludge blanket (UASB) reactor with synthetic wastewater containing propionate as a sole carbon source was introduced. Under the hydraulic retention time (HRT) of 10 h and influent propionate of 2,000 mg/l condition, propionate removal was above 94% at 30-35°C, whereas propionate conversion was inhibited when temperature was suddenly decreased stepwise from 30°C to 25°C, to 20°C, and then to 18°C. After a long-term operation, the propionate removal at 25°C resumed to the value at 30- 35°C, whereas that at 20°C and 18°C was still lower than the value at 35°C by 8.1% and 20.7%, respectively. Microbial community composition analysis showed that Syntrophobacter and Pelotomaculum were the major propionate-oxidizing bacteria (POB), and most POB had not changed with temperature decrease in the UASB. However, two POB were enriched at 18°C, indicating they were low temperature tolerant. Methanosaeta and Methanospirillum were the dominant methanogens in this UASB and remained constant during temperature decrease. Although the POB and methanogenic composition hardly changed with temperature decrease, the specific CODPro removal rate of anaerobic sludge (SCRR) was reduced by 21.4%-46.4% compared with the control (35°C) in this system.


Individual variation in fathers' testosterone reactivity to infant distress predicts parenting behaviors with their 1-year-old infants.
Positive father involvement is associated with positive child outcomes. There is great variation in fathers' involvement and fathering behaviors, and men's testosterone (T) has been proposed as a potential biological contributor to paternal involvement. Previous studies investigating testosterone changes in response to father-infant interactions or exposure to infant cues were unclear as to whether individual variation in T is predictive of fathering behavior. We show that individual variation in fathers' T reactivity to their infants during a challenging laboratory paradigm (Strange Situation) uniquely predicted fathers' positive parenting behaviors during a subsequent father-infant interaction, in addition to other psychosocial determinants of paternal involvement, such as dispositional empathy and marital quality. The findings have implications for understanding fathering behaviors and how fathers can contribute to their children's socioemotional development.


Foveal Structure in Macula-off Rhegmatogenous Retinal Detachment after Scleral Buckling or Vitrectomy.
To evaluate foveal microstructural changes and to determine its association with visual outcomes after reattachment of rhegmatogenous retinal detachments (RRDs) by scleral buckling (SB) or pars plana vitrectomy (PPV). Using spectral domain optical coherence tomography (SD-OCT), foveal microstructure in eyes with macula-off RRD were studied 1, 3, 6, 9, 12 and 15 months after PPV or SB and correlated with visual outcomes. Forty-two eyes were included in the final analysis. Even with improved microstructural changes and normalization of retinal structures on OCT, final visual acuity was not correlated with microstructural changes in eyes undergoing PPV. In the SB group, final visual acuity was significantly correlated with an intact inner segment/outer segment (IS/OS) junction (P = 0.013). There was no significant correlation between final visual acuity and presence of subretinal fluid (SRF) in either group. After SB, eyes with an intact IS/OS junction had better final visual acuity. In the PPV group, there was no significant correlation between microstructural changes and visual acuity. The presence of SRF did not influence final visual acuity in both groups.


Genetic Epidemiology in Latin America: Identifying Strong Genetic Proxies for Complex Disease Risk Factors.
Epidemiology seeks to determine the causal effects of exposures on outcomes related to the health and wellbeing of populations. Observational studies, one of the most commonly used designs in epidemiology, can be biased due to confounding and reverse causation, which makes it difficult to establish causal relationships. In recent times, genetically informed methods, like Mendelian randomization (MR), have been developed in an attempt to overcome these disadvantages. MR relies on the association of genetic variants with outcomes of interest, where the genetic variants are proxies or instruments for modifiable exposures. Because genotypes are sorted independently and at random at the time of conception, they are less prone to confounding and reverse causation. Implementation of MR depends on, among other things, a strong association of the genetic variants with the exposure, which has usually been defined via genome-wide association studies (GWAS). Because GWAS have been most often carried out in European populations, the limited identification of strong instruments in other populations poses a major problem for the application of MR in Latin America. We suggest potential solutions that can be realized with the resources at hand and others that will have to wait for increased funding and access to technology.


Effects of Supervised vs. Unsupervised Training Programs on Balance and Muscle Strength in Older Adults: A Systematic Review and Meta-Analysis.
Balance and resistance training can improve healthy older adults' balance and muscle strength. Delivering such exercise programs at home without supervision may facilitate participation for older adults because they do not have to leave their homes. To date, no systematic literature analysis has been conducted to determine if supervision affects the effectiveness of these programs to improve healthy older adults' balance and muscle strength/power. The objective of this systematic review and meta-analysis was to quantify the effectiveness of supervised vs. unsupervised balance and/or resistance training programs on measures of balance and muscle strength/power in healthy older adults. In addition, the impact of supervision on training-induced adaptive processes was evaluated in the form of dose-response relationships by analyzing randomized controlled trials that compared supervised with unsupervised trials. A computerized systematic literature search was performed in the electronic databases PubMed, Web of Science, and SportDiscus to detect articles examining the role of supervision in balance and/or resistance training in older adults. The initially identified 6041 articles were systematically screened. Studies were included if they examined balance and/or resistance training in adults aged ≥65 years with no relevant diseases and registered at least one behavioral balance (e.g., time during single leg stance) and/or muscle strength/power outcome (e.g., time for 5-Times-Chair-Rise-Test). Finally, 11 studies were eligible for inclusion in this meta-analysis. Weighted mean standardized mean differences between subjects (SMDbs) of supervised vs. unsupervised balance/resistance training studies were calculated. The included studies were coded for the following variables: number of participants, sex, age, number and type of interventions, type of balance/strength tests, and change (%) from pre- to post-intervention values. Additionally, we coded training according to the following modalities: period, frequency, volume, modalities of supervision (i.e., number of supervised/unsupervised sessions within the supervised or unsupervised training groups, respectively). Heterogeneity was computed using I 2 and χ 2 statistics. The methodological quality of the included studies was evaluated using the Physiotherapy Evidence Database scale. Our analyses revealed that in older adults, supervised balance/resistance training was superior compared with unsupervised balance/resistance training in improving measures of static steady-state balance (mean SMDbs = 0.28, p = 0.39), dynamic steady-state balance (mean SMDbs = 0.35, p = 0.02), proactive balance (mean SMDbs = 0.24, p = 0.05), balance test batteries (mean SMDbs = 0.53, p = 0.02), and measures of muscle strength/power (mean SMDbs = 0.51, p = 0.04). Regarding the examined dose-response relationships, our analyses showed that a number of 10-29 additional supervised sessions in the supervised training groups compared with the unsupervised training groups resulted in the largest effects for static steady-state balance (mean SMDbs = 0.35), dynamic steady-state balance (mean SMDbs = 0.37), and muscle strength/power (mean SMDbs = 1.12). Further, ≥30 additional supervised sessions in the supervised training groups were needed to produce the largest effects on proactive balance (mean SMDbs = 0.30) and balance test batteries (mean SMDbs = 0.77). Effects in favor of supervised programs were larger for studies that did not include any supervised sessions in their unsupervised programs (mean SMDbs: 0.28-1.24) compared with studies that implemented a few supervised sessions in their unsupervised programs (e.g., three supervised sessions throughout the entire intervention program; SMDbs: -0.06 to 0.41). The present findings have to be interpreted with caution because of the low number of eligible studies and the moderate methodological quality of the included studies, which is indicated by a median Physiotherapy Evidence Database scale score of 5. Furthermore, we indirectly compared dose-response relationships across studies and not from single controlled studies. Our analyses suggest that supervised balance and/or resistance training improved measures of balance and muscle strength/power to a greater extent than unsupervised programs in older adults. Owing to the small number of available studies, we were unable to establish a clear dose-response relationship with regard to the impact of supervision. However, the positive effects of supervised training are particularly prominent when compared with completely unsupervised training programs. It is therefore recommended to include supervised sessions (i.e., two out of three sessions/week) in balance/resistance training programs to effectively improve balance and muscle strength/power in older adults.


Efficacy and Safety of Apixaban Versus Warfarin in Patients with Atrial Fibrillation and a History of Cancer: Insights from the ARISTOTLE Trial.
Cancer is associated with a prothrombotic state and increases the risk of thrombotic events in patients with atrial fibrillation. We described the clinical characteristics and outcomes and assessed the safety and efficacy of apixaban versus warfarin in patients with atrial fibrillation and cancer in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. The association between cancer and clinical outcomes was assessed using Cox regression models. At baseline, 1236 patients (6.8%) had a history of cancer; 12.7% had active cancer, and 87.3% had remote cancer. There were no significant associations between history of cancer and stroke/systemic embolism, major bleeding, or death. The effect of apixaban versus warfarin for the prevention of stroke/systemic embolism was consistent among patients with a history of cancer (event/100 patient-years = 1.4 vs 1.2; hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.53-2.26) and no cancer (1.3 vs 1.6; HR, 0.77; 95% CI, 0.64-0.93) (P interaction = .37). The safety and efficacy of apixaban versus warfarin were preserved among patients with and without active cancer. Apixaban was associated with a greater benefit for the composite of stroke/systemic embolism, myocardial infarction, and death in active cancer (HR, 0.30; 95% CI, 0.11-0.83) versus without cancer (HR, 0.86; 95% CI, 0.78-0.95), but not in remote cancer (HR, 1.46; 95% CI, 1.01-2.10) (interaction P = .0028). Cancer was not associated with a higher risk of stroke. The superior efficacy and safety of apixaban versus warfarin were consistent in patients with and without cancer. Our positive findings regarding apixaban use in patients with atrial fibrillation and cancer are exploratory and promising, but warrant further evaluation.


[Acute pulmonary embolism following lung resection: report of two cases].
We reported 2 cases of acute pulmonary embolism after resection for lung cancer. A 47-year-old male was admitted to our hospital with ground-glass opacity (GGO) on a chest computed tomography (CT). We performed a right upper lobectomy and node dissection (ND) 2a dissection. Two days after the operation, he developed hypotension and hypoxemia. He was diagnosed as acute pulmonary embolism by chest CT and lung scintigram. A 68-year-old women was performed right S6 segmentectomy for lung cancer. The next day, she complained of sudden chest discomfort and dyspnea. She was diagnosed as acute pulmonary embolism by chest CT. Immediately, we started anticoagration therapy with heparin and their condition were improved. It was very important to early diagnose and start anticoagration therapy immediately for acute pulumonary embolism.


[Thyroid dysfunction and thyroid antibodies in a population group over the age of 70. A prevalence study from Oslo and Naeröy].
The prevalence of thyroid dysfunction and thyroid antibodies was investigated in a small rural community (Naerøy) and in Oslo. Attendance rates in Naerøy and Oslo were 99 and 71%, respectively. The prevalence of undiagnosed latent hypothyroidism and primary hypothyroidism was 4.0 and 5.3% in women in Oslo and Naerøy respectively and 0 and 3.5% in men. Undiagnosed hyperthyroidism was detected in 1.2% of men in Naerøy and in 1% of women in Oslo. Antibody to the thyroid microsomal antigen in titre greater than or equal to 400 was detected in 10.2 and 17.5% of women and 7.3 and 7.2% of men in Oslo and Naerøy, respectively. Among women with antibody to the thyroid microsomal antigen in both Oslo and Naerøy, and among men in Naerøy, the prevalence of past or present thyroid dysfunction was increased.


Effect of tooth whitening strips on fatigue resistance and flexural strength of bovine dentin in vitro.
To determine the effects of whitening strips on bovine dentin fatigue resistance and flexural strength in vitro. A total of eighty bovine dentin specimens (2x2x17mm) were treated with either: control glycerine gel on plastic film wrap or whitening strips containing 9.5% hydrogen peroxide. Treatment was applied for 30 minutes, twice a day, for 1- or 4-weeks. After the last treatment, ten specimens per group were randomly selected to undergo fatigue testing (106 cycles, 3Hz, 20N) while the other ten were subjected to flexural strength testing after ten days of storage in artificial saliva. Kaplan-Meier method with a log rank test, Wilcoxon test and Cox regression were used to assess fatigue test results (p<0.05). One-way ANOVA and Tukey's tests were used to compare the flexural strength results (p<0.05). There were significant differences in survival during the fatigue test among the groups (p<0.001). Treatment (control or bleach) was a significant factor for specimen survival (p<0.001, Exp(B) = 33.45). There were significant differences in mean flexural strength (p<0.001). No significant difference was found between "1-wk control" and "4-wk control". The mean flexural strength and fatigue resistance of the "4-wk bleach" were significantly lower than all the other groups. The use of whitening strips reduced the fatigue resistance and flexural strength of bovine dentin in vitro. Until the effect of whitening strips on mechanical properties of human dentin is fully elucidated, it remains prudent to advise patients to avoid excessive direct use of whitening strips on dentin.


Metal-ligand delocalization and spin density in the CuCl2 and [CuCl4](2-) molecules: Some insights from wave function theory.
The aim of this paper is to unravel the physical phenomena involved in the calculation of the spin density of the CuCl2 and [CuCl4](2-) systems using wave function methods. Various types of wave functions are used here, both variational and perturbative, to analyse the effects impacting the spin density. It is found that the spin density on the chlorine ligands strongly depends on the mixing between two types of valence bond structures. It is demonstrated that the main difficulties found in most of the previous studies based on wave function methods come from the fact that each valence bond structure requires a different set of molecular orbitals and that using a unique set of molecular orbitals in a variational procedure leads to the removal of one of them from the wave function. Starting from these results, a method to compute the spin density at a reasonable computational cost is proposed.


[Medical aspect of the winter march of the Fifth Regiment of the Eighth Military Division in the winter of 1902 - particularly concerning the cause of Major Yamaguchi's death].
Two hundred and ten military soldiers of the Fifth Regiment of the Eighth Division of the Japan Imperial Army joined a marching practice in the end of January, 1902, but 193 soldiers out of 210 died due to severe frost-bite during stormy weather and only seventeen, including Major Yamaguchi, were rescued to survive and brought to the Veteran's Administration Hospital at Aomori. This accident was most tragic and world-shaking for the Japanese people as well as for the Japanese Imperial Army. In December of 1991, an admission record of the Veteran's Administration Hospital at Aomori was found in the residence of Dr. Murakami of Aomori City. Judging from its handwriting, this record was written by a military physician Ki-ichi Murakami, Dr. Murakami's uncle. The record describes the details of seventeen patients, most of whom were severely injured and frost-bitten during the winter march. The content of this newly discovered record is similar to the report written by the military physicians of the Fifth Regiment which appeared in the Japan Imperial Military Medical Journal, but a more detailed description about Major Yamaguchi's vital signs, and symptoms of his frost-bite were found in the former. In the journal, Major Yamaguchi was reported to have died because of sudden cardiac arrest but Jiro Nitta described in his novel "Death March on Mount Hakkoda" that he committed suicide using his gun. However, this record strongly tells us that both of his hands, as well as both lower extremities, were severely frost-bitten and swollen and that he could not pull the trigger of his gun with his fingers. Since Jiro Nitta's novel has been published, it is widely accepted that Major Yamaguchi committed suicide with his gun. But we do not have any definite proof to substantiate his suicide. The present detailed survey on the medical references strongly suggests that he could not have pulled his gun's trigger by himself.


Looking Forward and Looking Back: Older Adults' Views of the Impacts of Stopping Driving.
This project aimed to identify the impact of driving cessation from the perspectives of older drivers and former drivers. Participants included 17 adults aged 65-88 years residing in a city in Northwestern Ontario, Canada. Using a semi-structured interview guide (with questions regarding mobility, personal impact, impact on others, engagement with life, and finances), two focus groups were held with nine current drivers, and one-on-one interviews were held with six former drivers and two current drivers. Two themes emerged concerning stopping driving. The first theme included discussions on experiencing lifestyle changes, relationship impacts, and emotional impacts. The second, the adjustment to stopping driving, included practical adaptations, and emotional responses such as appreciation, resistance, acceptance, and being positive. Although the impacts of stopping driving were substantial, there were few discrepancies between what was anticipated and what was experienced. This information could assist with developing interventions to ease the transition to former-driver status.


Rationale and application of beta-2-microglobulin measurements to detect acute transplant rejection.
Serum and urinary concentrations of beta 2-microglobulin were measured for the first 21 days after renal transplantation to aid in diagnosis of acute rejection. Criteria developed after study of 15 patients were applied to the entire group of 31 consecutive cases. 29 instances meeting our criteria were identified in 651 days at risk and were associated with a mean maximal increase of serum creatinine of 74.8%. beta 2-Microglobulin methods may make possible detection of what is now subclinical rejection. beta 2-Microglobulin methods, however, are an adjunct to, not a replacement for classical methods for detecting acute rejection.


Behaviour, knowledge and reactions concerning sexually transmitted diseases: implications for partner notification in Lusaka.
Available data show that STDs and their consequences are a major health problem in Zambia. This study focuses on factors which could have implications for partner notification, as a tool for prevention. Fifty women and fifty men with STD were interviewed at two outpatient clinics in Lusaka, where partner notification is not functioning optimally. A majority of the sexual partners during the last three months were known by the patients who also stated a willingness to bring more partners than they were asked to do. Women had symptoms for a longer period than men before they came for treatment. They were less aware of symptoms connected with STD and a majority of them did not know that they were receiving treatment for STD. The communication between the health care provider and the patients about disease, treatment and partner notification needs to be improved especially for women.


Catalytic Decoupling of Quantum Information.
The decoupling technique is a fundamental tool in quantum information theory with applications ranging from thermodynamics to many-body physics and black hole radiation whereby a quantum system is decoupled from another one by discarding an appropriately chosen part of it. Here, we introduce catalytic decoupling, i.e., decoupling with the help of an independent system. Thereby, we remove a restriction on the standard decoupling notion and present a tight characterization in terms of the max-mutual information. The novel notion unifies various tasks and leads to a resource theory of decoupling.


Clinical Study of Sentinel Lymph Node Detection to Evaluate Pelvic Lymph Node Metastasis to Determine the Prognosis of Patients with Early Cervical Cancer.
Lymph node status is one of the most important prognostic factors for uterine cervical cancer. Sentinel lymph node (SLN) biopsy has emerged as a potential alternative to systematic lymphadenectomy for the lymph node mapping in such patients. However, the SLN metastasis detection via SLN biopsy in early-stage cervical cancer remains controversial. The current study is aimed at investigating the feasibility and accuracy of combined tracer method for localization of SLN in initial stages of cervical cancer and to evaluate the clinical value of SLN biopsy in replacing pelvic lymph node resection. We retrospectively reviewed 348 cases who were admitted to the Department of Gynecologic Oncology, Shandong Provincial Cancer Hospital, China, between February 2003 and June 2018 with FIGO stage IA2 to IIA2 cervical cancer and undergone through SLN biopsy. Methylthioninium chloride was injected in combination with 99mtechnetium-labeled sulfur colloid prior to surgery to these patients. SLNs were identified intraoperatively, excised, and subsequently submitted to fast frozen section. The detection rates, accuracy, sensitivity, coincidence rate, false negative rate, and negative predictive values of these cases were estimated, and the follow-up outcomes were carefully observed. Chi squared test or Fisher's exact test was employed for a comparison of the categorical variables. Univariate and multivariate Cox proportional hazard models were used for estimation of relationships between overall survival (OS) and disease-free survival (DFS) and prognostic factors. The total detection rate of SLN was 97.1% (338/348), and identification of bilateral SLN was successful in 237 patients (70.1%). The patient's tumor size, FIGO stage, lymph node metastasis, and depth of invasion had statistically significant differences in SLN detection rates. The detection rate had inverse relation with tumors size (>4 cm), invasive depth > 2/3, lymph node positive, late staging, and preoperative radiotherapy. 117 positive SLNs were detected in 73 patients. The negative predictive value, sensitivity, false negative rate, and coincidence rate and were 97.7%, 92.4%, 7.6%, and 95.4%, respectively. In patients whose tumor size were ≦ 4 cm, the false negative rate was 4.55% (2/44), whereas it was 0 in patients with tumor size≦2 cm. The respective 1, 3, and 5-year OS was 100%, 94.8%, and 91.8%, respectively, whereas DFS rate for 1, 3, and 5 years was 96.7%, 92%, and 89.6%, respectively. The lymph node was positive, tumor size, the depth of invasion, and staging were statistically different from the recurrence rate and survival rate of patients (p < 0.05). When tumor metastasis exceeded SLN, the recurrence rate was significantly increased, and survival rate is significantly reduced (p < 0.05, p < 0.01, p < 0.05, respectively). The identification of SLN combined with 99mtechnetium-labeled sulfur colloid and methylthioninium chloride has a good accuracy and is safe for the assessment of the status of pelvic nodes in patients with initial stage cervical cancer. Nuclide as a tracer has low dependence on objective conditions and doctors' technology and has a good detection rate. In our study, we believe that SLN biopsy is feasible when the tumor is ≦ 4 cm. Large scale clinical trials are required in China expand the sample size and validate the results of this study.


Life-history evolution in ants: the case of Cardiocondyla.
Ants are important components of most terrestrial habitats, and a better knowledge of the diversity of their life histories is essential to understand many aspects of ecosystem functioning. The myrmicine genus Cardiocondyla shows a wide range of colony structures, reproductive behaviours, queen and male lifespans, and habitat use. Reconstructing the evolutionary pathways of individual and social phenotypic traits suggests that the ancestral life history of Cardiocondyla was characterized by the presence of multiple, short-lived queens in small-sized colonies and a male polyphenism with winged dispersers and wingless fighters, which engage in lethal combat over female sexuals within their natal nests. Single queening, queen polyphenism, the loss of winged males and tolerance among wingless males appear to be derived traits that evolved with changes in nesting habits, colony size and the spread from tropical to seasonal environments. The aim of this review is to bring together the information on life-history evolution in Cardiocondyla and to highlight the suitability of this genus for functional genomic studies of adaptation, phenotypic plasticity, senescence, invasiveness and other key life-history traits of ants.


Transplant tumor registry: donor related malignancies.
Transmission of donor malignancies has been intermittently reported since the early days of clinical transplantation. The incidence of United States donor related malignancies has not previously been documented. All donor related malignancies reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing from 4/1/94-7/1/01 in a cohort of 34,933 cadaveric donors and 108,062 recipients were investigated by contacting the transplant centers to verify that the reported tumors were of donor origin. Time and mode of discovery, as well as graft and patient outcome, were determined. The status of other recipients from the donor was investigated. A total of 21 donor related malignancies from 14 cadaveric and 3 living donors were reported. Fifteen tumors were donor transmitted and 6 were donor derived. Transmitted tumors are malignancies that existed in the donor at the time of transplantation. Derived tumors are de novo tumors that develop in transplanted donor hematogenous or lymphoid cells after transplantation. The cadaveric donor related tumor rate is 0.04% (14 of 34,993). The donor related tumor rate among transplanted cadaveric organs is 0.017% (18 of 108,062). Among patients developing donor related malignancies, the overall mortality rate was 38%, with that of transmitted tumors being 46% and derived tumors being 33%. The cadaveric donor related tumor mortality rate is 0.007% (8 of 108,062). The United States incidence of donor related tumors is extremely small. The donor related tumor death rate is also extremely small, particularly when compared with waiting-list mortality.


Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study.
This work explores a new radiation therapy approach which might trigger a renewed use of neon and heavier ions to treat cancers. These ions were shown to be extremely efficient in radioresistant tumor killing. Unfortunately, the efficient region also extends into the normal tissue in front of the tumor. The strategy the authors propose is to profit from the well-established sparing effect of thin spatially fractionated beams, so that the impact on normal tissues might be minimized while a high tumor control is achieved. The main goal of this work is to provide a proof of concept of this new approach. With that aim, a dosimetric study was carried out as a first step to evaluate the interest of further explorations of this avenue. The gate/geant4 v.6.1 Monte Carlo simulation platform was employed to simulate arrays of rectangular minibeams (700 μm × 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed with a 2 cm-long spread-out Bragg peak centered at 7 cm-depth. Dose distributions in a water phantom were scored considering two minibeams center-to-center distances: 1400 and 3500 μm. Peak and valley doses, peak-to-valley dose ratios (PVDRs), beam penumbras, and relative contribution of nuclear fragments and electromagnetic processes were assessed as figures of merit. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions. Extremely high PVDR values (>100) and low valley doses were obtained. The higher the atomic number (Z) of the primary ion is, the lower the valleys and the narrower the penumbras. Although the yield of secondary nuclear products increases with Z, the actual dose being deposited by the secondary nuclear fragments in the valleys starts to be the dominant contribution at deeper points, helping in the sparing of proximal normal tissues. Additionally, a wider center-to-center distance leads to a minimized contribution of heavier secondary fragments in valleys. The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of neon and heavier ions for the treatment of radioresistant tumors, while preserving normal tissues. The authors' results support the further exploration of this avenue. Next steps include the realization of biological experiment to confirm the shifting of normal tissue complication probability curves.


Induction of cross-reactive antibodies by immunization of healthy adults with types Ia and Ib group B streptococcal polysaccharide-tetanus toxoid conjugate vaccines.
Types Ia and Ib group B streptococcal (GBS) capsular polysaccharides (PSs) are structural isomers but are antigenically distinct. Immunization of healthy adults with GBS type Ia PS-tetanus toxoid (Ia-TT) or Ib-TT glycoconjugate vaccines induced > or = 4-fold increases in specific immunoglobulin G to the heterologous PS in more than two-thirds of subjects. Ib-TT vaccine-induced IgG bound with substantially higher affinity to homologous (Ib) than to heterologous (Ia) PS and promoted opsonophagocytic killing of GBS type Ib but not type Ia organisms. The failure of the Ib-TT- and Ia-TT-induced human antibodies to kill bacteria of the cross-reactive serotype contrasts with the results of previous studies in animals. Inhibition enzyme-linked immunosorbent assays demonstrated that Ib-TT-induced IgG to the homologous PS bound mainly to native Ib PS, whereas the cross-reactive antibodies recognized both native and derivative PSs. These results indicate that GBS Ia and Ib PSs should be included in a multivalent conjugate vaccine to prevent GBS disease.


Accuracy of 30-minute indirect calorimetry studies in predicting 24-hour energy expenditure in mechanically ventilated, critically ill patients.
There is no consensus regarding the optimal duration of measurement or time of day to perform indirect calorimetry (IC). Energy expenditure (EE) varies at different times of day and with different activity levels. We sought to assess the variability of EE in mechanically ventilated patients over a 24-hour period and the accuracy of 30-minute IC studies in predicting the 24-hour energy expenditure (EE24). The study was a prospective comparison between the resting EE obtained by 30-minute measurement of IC and EE values obtained from 24-hour measurements. Tests were performed in the Medical Intensive Care Unit (MICU) of a tertiary care, university hospital. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured for 24 hours in eight ventilated patients. Measurements were made every 3 minutes and used to calculate 30-minute and 24-hour oxygen consumption values. EE24 was calculated using the modified Weir equation. Each 30-minute interval was compared with the value obtained from the 24-hour measurement. Three hundred forty-one of 384 30-minute intervals remained for analysis. Average EE24 measured was 1490 +/- 486 kcal/d. Average EE24 predicted by extrapolation from 30-minute studies was 1501 +/- 503 kcal/d, with a mean difference of 0 +/- 209 kcal/d from the measured 24-hour values (range: -1068 to +585 kcal/d). Thirty-minute studies were within 20% of 24-hour measurements for 89% of intervals. The difference between 24-hour and 30-minute studies correlated with changes in minute ventilation (VE), heart rate, systolic blood pressure, and breath rate from their 24-hour means (p < .001). The mean error of EE estimate was greatest between 3 and 11 PM (p < .001). We conclude the following: (1) EE in MICU patients is variable; (2) 30-minute IC studies predict measured EE24 acceptably well for clinical purposes; and (3) accuracy is maximized if a 30-minute study is performed between 11 PM and 3 PM, and when Ve, heart rate, systolic blood pressure, and breath rate are near the day's average.


Near-Infrared-II Fluorophore with Inverted Dependence of Fluorescence Quantum Yield on Polarity as Potent Phototheranostics for Fluorescence-Image-Guided Phototherapy of Tumors.
Organic phototheranostics simultaneously having fluorescence in the second near-infrared (NIR-II, 1000-1700 nm) window, and photothermal and photodynamic functions possess great prospects in tumor diagnosis and therapy. However, such phototheranostics generally suffer from low brightness and poor photodynamic performance due to severe solvatochromism. Herein, an organic NIR-II fluorophore AS1, which possesses an inverted dependence of fluorescence quantum yield on polarity, is reported to serve as potent phototheranostics for tumor diagnosis and therapy. After encapsulation of AS1 into nanostructures, the obtained phototheranostics (AS1R ) exhibit high extinction coefficients (e.g., 68200 L mol-1 cm-1 at 808 nm), NIR-II emission with high fluorescence quantum yield up to 4.7% beyond 1000 nm, photothermal conversion efficiency of ≈65%, and 1 O2 quantum yield up to 4.1%. The characterization of photophysical properties demonstrates that AS1R is superior to other types of organic phototheranostics in brightness, photothermal effect, and photodynamic performance at the same mass concentration. The excellent phototheranostic performance of AS1R enables clear visualization and complete elimination of tumors using a single and low injection dose. This study demonstrates the merits and prospects of NIR-II fluorophore with inverted polarity dependence of fluorescence quantum yield as high-performance phototheranostic agents for fluorescence imaging and phototherapy of tumors.


Kinetically driven island morphology in growth on strained Cu(100).
We study the effects of strain on the monomer and dimer diffusion mechanisms and island morphology during the growth of Cu on a biaxially strained Cu(100) substrate. We find an approximately linear dependence of the activation barriers on strain. In particular, while hopping is favored for compressive and/or small (<2%) tensile strain, for greater than 2% tensile strain, the exchange mechanism is favored. We then present the results of temperature-accelerated dynamics simulations of submonolayer growth at 200 K. For the case of 2% compressive strain we find that, as in previous kinetic Monte Carlo simulations of Cu/Ni(100) growth, the competition between island growth and multi-atom relaxation ("pop-out") events leads to an island morphology with a mixture of open and closed steps. At slightly higher coverage, island coalescence then leads to elongated islands. However, annealing leads to a significant decrease in the number of open steps. In contrast, for the case of 8% tensile strain, only one large strongly anisotropic island is formed. Surprisingly, we find that despite the large strain, the island anisotropy is not due to energetics but is instead due to anisotropic attachment barriers that favor the exchange-mediated attachment of monomers to corners over close-packed step-edges. An explanation for the asymmetry in attachment barriers is provided. Our results provide a new general kinetic mechanism for the formation of anisotropic islands in the presence of isotropic diffusion and tensile strain.


Otx genes in the evolution of the vertebrate brain.
Only until a decade ago, animal phylogeny was traditionally based on the assumption that evolution of bilaterians went from simple to complex through gradual steps in which the extant species would represent grades of intermediate complexity that reflect the organizational levels of their ancestors. The advent of more sophisticated molecular biology techniques combined to an increasing variety of functional experiments has provided new tools, which lead us to consider evolutionary studies under a brand new light. An ancestral versus derived low-complexity of a given organism has now to be carefully re-assessed and also the molecular data so far accumulated needs to be re-evaluated. Conserved gene families expressed in the nervous system of all the species have been extensively used to reconstruct evolutionary steps, which may lead to identify the morphological as well as molecular features of the last common ancestor of bilaterians (Urbilateria). The Otx gene family is among these and will be here reviewed.


Association between myasthenia gravis and malignant lymphoma.
A reticulum cell sarcoma was diagnosed in a myasthenic patient 14 years after the first manifestations of myasthenia gravis. The association of myasthenia and malignancy, especially lymphoreticular, is discussed in view of an increasing number of similar reports in the literature. It is suggested that autoimmune diseases, myasthenia gravis and malignant processes might have a common underlying abnormal immune state related to thymic pathology.


Uncertainty analysis of integrated gasification combined cycle systems based on Frame 7H versus 7F gas turbines.
Integrated gasification combined cycle (IGCC) technology is a promising alternative for clean generation of power and coproduction of chemicals from coal and other feedstocks. Advanced concepts for IGCC systems that incorporate state-of-the-art gas turbine systems, however, are not commercially demonstrated. Therefore, there is uncertainty regarding the future commercial-scale performance, emissions, and cost of such technologies. The Frame 7F gas turbine represents current state-of-practice, whereas the Frame 7H is the most recently introduced advanced commercial gas turbine. The objective of this study was to evaluate the risks and potential payoffs of IGCC technology based on different gas turbine combined cycle designs. Models of entrained-flow gasifier-based IGCC systems with Frame 7F (IGCC-7F) and 7H gas turbine combined cycles (IGCC-7H) were developed in ASPEN Plus. An uncertainty analysis was conducted. Gasifier carbon conversion and project cost uncertainty are identified as the most important uncertain inputs with respect to system performance and cost. The uncertainties in the difference of the efficiencies and costs for the two systems are characterized. Despite uncertainty, the IGCC-7H system is robustly preferred to the IGCC-7F system. Advances in gas turbine design will improve the performance, emissions, and cost of IGCC systems. The implications of this study for decision-making regarding technology selection, research planning, and plant operation are discussed.


Navigating neocortical neurogenesis and neuronal specification: a positional information system encoded by neurogenetic gradients.
The projection neurons of the neocortex are produced in the pseudostratified ventricular epithelium (PVE) lining the embryonic lateral ventricles. Over a 7 d period in mouse, these neurons arise in an overlapping layer VI-to-II sequence and in an anterolateral to posteromedial gradient [the transverse neurogenetic gradient (TNG)]. At any time in the 7 d neurogenetic interval, a given PVE cell must know what class of precursor cell or neuron to form next. How this information is encoded in the PVE is not known. With comparative experiments in wild-type and double-transgenic mice, overexpressing the cell cycle inhibitor p27(Kip1), we show that a gradient of expression of Lhx2 (inferred from its mRNA levels), a LIM homeodomain transcription factor, together with a gradient in duration of the G1 phase of the cell cycle (T(G1)), are sufficient to specify a positional mapping system that informs the PVE cell what class of neuron to produce next. Lhx2 likely is representative of an entire class of transcription factors expressed along the TNG. This mapping system consisting of a combination of signals from two different sources is a novel perspective on the source of positional information for neuronal specification in the developing CNS.


Extracorporeal membrane oxygenation (ECMO) for near-fatal asthma refractory to conventional ventilation.
We describe a case of near-fatal asthma, treated successfully by initiation of extracorporeal membrane oxygenation (ECMO). A 29-year-old woman, known asthmatic on steroid inhalers, inhaled/nebulised bronchodilators, long-term oral prednisolone, theophylline and montelukast, presented with acute shortness of breath. She deteriorated following initial treatment with nebulised bronchodilators and magnesium sulfate requiring intubation and mechanical ventilation. Severe bronchospasm ensued following mechanical ventilation and peak airway pressures remained at 55 cm H2O with intrinsic positive end expiratory pressure(PEEP) of 14 cm H2O. Despite treatment with sedation, paralysis, intravenous salbutamol and inhaled sevoflurane, her condition deteriorated. She was commenced on mobile ECMO by the retrieval team. While on ECMO, her CO2 normalised within 48 hours. She was extubated within 72 hours of initiating ECMO and was discharged to the ward next day. We reiterate that ECMO should be considered sooner for status asthmatics not responding to maximal pharmacological therapy and ventilatory support to prevent ongoing lung injury and mortality.


Design and fabrication of an achromatic infrared wave plate with Sb-Ge-Sn-S system chalcogenide glass.
We designed and fabricated an achromatic infrared wave plate. To examine its phase retardation characteristics, the birefringence was calculated using the effective medium theory. A wave plate with a subwavelength grating was fabricated by direct imprint lithography on a low toxic chalcogenide glass (Sb-Ge-Sn-S system) based on calculated results. As a result of imprinting onto chalcogenide glass by a glassy carbon mold, a grating with 1.63 μm depth, a fill factor of 0.7, and a 3 μm period was obtained. The phase retardation of the elements reached around 30° in the 8.5-10.5 μm wavelength range. The fabrication of the infrared wave plate is less costly compared with conventional crystalline wave plates.


Psychotherapy dropouts: differences by modality, license, and DSM-IV diagnosis.
Dropouts are frequent in mental health care. Several client factors have been identified as dropout predictors, including ethnic minority status, race, low SES, and more severe symptoms. Research on therapist and process variables is less common, and findings are inconsistent. This study used administrative data for 434,317 patients from CIGNA Behavioral Health (CIGNA) to examine dropout rates by profession of provider, therapy modality, and DSM-IV diagnosis. Results indicate that among the providers, MFTs have the lowest dropout rates in the CIGNA network. Of the therapy modalities, individual therapy is associated with lower dropout rates than family therapy. Mood and anxiety disorders have lower dropout rates than other diagnosis categories, while schizophrenia, psychotic, and substance use disorders have the highest dropout rates.


Calibrated propensity score method for survey nonresponse in cluster sampling.
Weighting adjustment is commonly used in survey sampling to correct for unit nonresponse. In cluster sampling, the missingness indicators are often correlated within clusters and the response mechanism is subject to cluster-specific nonignorable missingness. Based on a parametric working model for the response mechanism that incorporates cluster-specific nonignorable missingness, we propose a method of weighting adjustment. We provide a consistent estimator of the mean or totals in cases where the study variable follows a generalized linear mixed-effects model. The proposed method is robust in the sense that the consistency of the estimator does not require correct specification of the functional forms of the response and outcome models. A consistent variance estimator based on Taylor linearization is also proposed. Numerical results, including a simulation and a real-data application, are presented.


Middle Ear Obliteration with Blind-Sac Closure of the External Auditory Canal for Spontaneous CSF Otorrhea.
Outcome Objectives To (1) identify unique features of patients who underwent middle ear/mastoid obliteration with blind-sac closure of the external auditory canal for spontaneous cerebrospinal fluid (CSF) otorrhea and (2) explore outcomes. Study Design Case series with chart review. Setting Tertiary care center. Subjects and Methods Adults treated for spontaneous cerebrospinal fluid otorrhea from 2007 through 2015 were reviewed and stratified into 2 groups based on the surgery performed: (1) 11 patients underwent middle ear/mastoid obliteration with blind-sac closure of the external auditory canal and (2) 26 patients underwent other procedures. Demographics, body mass index, revised cardiac risk index, Duke Activity Status Index scores, and anticoagulation use were documented. Audiologic data were gathered from pre- and postoperative visits. The primary outcome measure was leak recurrence. Complications were tabulated. Results Poor preoperative hearing was a relative indication for obliteration. Obliteration patients had higher body mass index (43.2 vs 34.9 kg/m2; P < .05), incidence of super-morbid obesity (45% vs 7.6%; P = .015), anticoagulation usage (36% vs 0%; P = .004), cardiac risk scores (1.2 vs 0.1 dB; P < .0004), and Duke Activity Status Index scores. There was 1 leak recurrence (9%). Major and minor complication rates were 9% and 36%, respectively. Mean follow-up was 30.8 ± 8.6 months. Conclusion Middle ear and mastoid obliteration with blind-sac closure of the external auditory canal is effective for treating spontaneous CSF otorrhea. The small cohort reviewed did not experience any major perioperative morbidity. The technique may be best suited for patients with poor hearing, the infirm, and those in whom craniotomy is contraindicated.


[The contribution of nurse clinicians to home nursing practice].
Home nursing care enables the wishes of patients to be met and financial constraints to be taken into consideration. Through a global and transversal approach, the nurse clinician working in freelance practice offers her vision and her expertise in the field of nursing care. She draws on experiential knowledge and best practice recommendations and contributes to the improvement of patients' quality of life, within a multi-disciplinary team.


[Stress echocardiography: 4 years of experience at the Thoraxcenter].
In this article, we report the experience on stress echocardiography at the Thoraxcenter of Erasmus University of Rotterdam in the years 1990-1994. Different types of stress have been used in conjunction with ultrasound techniques. The results have been compared with other non-invasive methods (exercise ECG testing, myocardial perfusion scintigraphy with single photon emission computed tomography) and with coronary arteriography. Both the diagnostic and prognostic value of stress echocardiography have been assessed in different clinical situations, as in patients with chest pain and suspected or proven coronary artery disease, patients referred for percutaneous transluminal coronary angioplasty, patients referred for major non cardiac vascular surgery. After this period of validation, stress echocardiography has now a definite role in the clinical decision making for the evaluation of myocardial ischemia. The assessment of viable myocardium, especially in patients with advanced left ventricular dysfunction, is one of the major topic currently under investigation. Practical aspects of the interpretation of the tests, costs and organization of the stress echo laboratory, indications and newest research applications are also discussed.


Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) are associated with long term tramadol treatment-induced oxidative damage and hepatotoxicity.
Our objective was to figure out whether CYP2D6 gene polymorphisms may account for long term tramadol-induced oxidative stress and hepatotoxicity in 60 patients receiving chronic tramadol treatment in Neurology and Rheumatology Outpatients Clinic, Zagazig University Hospitals, Egypt. As expected, CYP2D6*1 allele (wild type) frequency was significantly greater than CYP2D6*DUP, CYP2D6*4 and CYP2D6*10 alleles in both chronically tramadol-treated and control groups. In tramadol-treated patients, CYP2D6*DUP allele carriers followed by those carrying CYP2D6*1, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D6*4&*10), suggesting oxidative stress. There were also significant increases in serum hepatic damage markers including alpha-glutathione transferase (α-GST) levels and liver function enzyme activities in *DUP and *1 carriers compared to carriers of other alleles. Moreover, we reported that in 42 patients with allele *1, tramadol caused mild to moderate hepatotoxicity (grades: 1-2) within 13-16 months while in 7 patients with duplicated allele (*DUP), tramadol caused moderate to severe hepatotoxicity (grades: 2-3) within 10-11 months (moderately longer period but shorter than that observed in allele *1), implying that exposure to tramadol for longer time in extensive and ultra-rapid metabolizers may contribute to hepatotoxicity development. Overall, our results suggest that CYP2D6 gene polymorphisms, particularly enhanced or normal function of CYP2D6, may increase the vulnerability to long term tramadol-induced hepatotoxicity through the enhancement of accumulation of tramadol bioactive metabolite (M1) and hence oxidative stress. Therefore, tramadol doses should be adjusted according to patient's CYP2D6 genotyping analysis to avoid hepatotoxicity.


Is the relationship between periodontitis and hyperlipidemia mediated by lipoprotein-associated inflammatory mediators?
The aim of this study was to evaluate the serum levels of oxidized low-density lipoprotein (oxLDL), anti-oxLDL, and myeloperoxidase (MPO) in hyperlipidemic patients with periodontal disease. This study included 123 patients with hyperlipidemia categorized based on metabolic control as mild to moderate (H1) (n=66) or poor (H2) (n=57), as well as systemically healthy controls (C) (n=68). Serum levels of lipids, oxLDL, anti-oxLDL, and MPO were evaluated, along with clinical periodontal parameters. The percentage of bleeding on probing (BOP%) and the clinical attachment level were significantly higher in the H2 group than in the C group. Patients with hyperlipidemia had a relatively high risk of developing periodontal disease. The oxLDL and anti-oxLDL levels were higher in H2 patients with periodontitis than in the control or H1 patients with periodontitis. In the H1 and H2 groups, the ratio of total cholesterol to high-density lipoprotein was significantly correlated with gingival index, BOP%, and oxLDL levels. Our findings indicate that the lipoprotein-associated inflammatory mediators of oxLDL, anti-oxLDL, and MPO may play an important role in the relationship between periodontal disease and hyperlipidemia.


Phase-space averaging and natural branching of nuclear paths for nonadiabatic electron wavepacket dynamics.
We propose a simple and tractable method to treat quantum electron wavepacket dynamics that nonadiabatically couples with "classical" nuclear motions in mixed quantum-classical representation. The electron wavepacket is propagated inducing electronic-state mixing along our proposed paths. It has been shown in our previous studies that classical force working on nuclei in a nonadiabatic region is represented in a matrix form (called the force matrix), and the solutions of the Hamilton canonical equations of motion for nuclei based on this force matrix give rise to a cascade of infinitely many branching paths when solved simultaneously with electronic-state mixing. As a tractable approximation to these rigorous solutions, we here devise a method to provide much simpler nonadiabatic paths: (i) extract one or a few number of representative paths by taking an average over the paths in phase space (not averaging over the forces) that should be otherwise undergo the fine branching. (ii) After the nonadiabatic coupling becomes sufficiently small, let these paths naturally branch by running them with their own individual eigenforces (the eigenvalues of the force matrix). Since the eigenforces coincide with the forces of adiabatic potential energy surfaces in the limit of zero nonadiabatic coupling, these branching paths eventually run on one of possible adiabatic potential energy surfaces, converging to a classical path (Born-Oppenheimer path). The paths thus created are theoretically satisfactory in that they realize the coherent mixing of electronic states in the manner of quantum entanglement and yet eventually become consistent with the Born-Oppenheimer classical trajectories. We test the present method numerically with the use of two- and three-state systems that are extracted from ab initio calculations for the excited states of LiH molecule.


Health informatics and analytics - building a program to integrate business analytics across clinical and administrative disciplines.
Health care organizations must develop integrated health information systems to respond to the numerous government mandates driving the movement toward reimbursement models emphasizing value-based and accountable care. Success in this transition requires integrated data analytics, supported by the combination of health informatics, interoperability, business process design, and advanced decision support tools. This case study presents the development of a master's level cross- and multidisciplinary informatics program offered through a business school. The program provides students from diverse backgrounds with the knowledge, leadership, and practical application skills of health informatics, information systems, and data analytics that bridge the interests of clinical and nonclinical professionals. This case presents the actions taken and challenges encountered in navigating intra-university politics, specifying curriculum, recruiting the requisite interdisciplinary faculty, innovating the educational format, managing students with diverse educational and professional backgrounds, and balancing multiple accreditation agencies.


Enhanced Charge Separation in Ternary Bulk-Heterojunction Organic Solar Cells by Fullerenes.
Carrier generation dynamics in binary PTB7-Th:COi8DFIC (1:1.5) and ternary PTB7-Th:COi8DFIC:PC71BM (1:1.05:0.45) composites were investigated to identify the origins of high power conversion efficiencies (PCEs) in ternary bulk-heterojunction (BHJ) organic solar cells. Steady-state photoluminescence and time-resolved photoinduced absorption spectroscopic analyses revealed that the ternary composite exhibited faster hole transfer from COi8DFIC to PTB7-Th (8 ps compared to 21 ps in the binary composite), which led to an improved exciton separation yield in COi8DFIC (94% compared to 68% in the binary composite). Improved intermixing of the component materials and efficient electron transfer from COi8DFIC to PC71BM facilitated enhancement in the hole transfer rate. The COi8DFIC-to-PC71BM electron transfer promoted an electron transport cascade over PTB7-Th, COi8DFIC, and PC71BM, which efficiently deactivated back-electron transfer (carrier recombination loss) from COi8DFIC to PTB7-Th at ∼160 ps and assisted in improving the PCE of the ternary BHJ cell (13.4% compared to 10.5% in the binary BHJ cell).


Induction of two distinct natural killer-cell populations, activated T cells and antineoplastic cytokines, by interleukin-2 therapy in children with solid tumors.
Children with poor prognoses regarding solid tumors have benefited from autologous bone marrow transplantation as a treatment modality. Posttransplantation adjuvant interleukin-2 (IL-2) therapy has previously been shown to improve prognosis in adults with neoplastic disease. The improved survival probability has been attributed to IL-2-mediated stimulation of the immune system and its antineoplastic activity. In this study, 10 pediatric patients with solid tumors in complete remission after autologous stem cell transplantation were treated with recombinant IL-2, which was administered in three 5-day cycles of continuous intravenous infusions with a 2-week rest in between cycles. We demonstrated that IL-2 therapy enhanced transplantation-related stimulation of the immune system, on both the cellular and humoral levels. Peripheral blood T and natural killer (NK) cells increased by the factors four and 14, respectively. Activation of the immune system was demonstrated by significantly elevated levels of soluble IL-2 receptor (IL-2R) and increased CD25 surface expression on T lymphocytes. IL-2 also induced significant proliferation of the CD56bright NK-cell subpopulation that appears post-bone marrow transplant (BMT) and is found only in minimal amounts in normal controls. In vivo and in vitro production of tumor cytotoxic cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was significantly stimulated following IL-2 therapy, further indicating IL-2-mediated stimulation of the antineoplastic activity of the immune system.


Laparoscopic adrenalectomy for pheochromocytoma: morbidity compared with adrenalectomy for tumors of other pathology.
We report our experience with laparoscopic adrenalectomy in nine patients with pheochromocytoma and compare the morbidity with that of laparoscopic adrenalectomy for tumors of other pathology. Between January 1997 and November 1999, nine patients underwent laparoscopic surgery for pheochromocytoma via a transperitoneal approach. Of the patients, eight had solitary tumors, and one presented with bilateral pheochromocytomas. The mean size of the tumors was 5.4 cm. The surgical outcomes of the 9 patients were compared with those of 28 patients with adrenal tumors of other pathology (primary aldosteronism in 15 patients, Cushing syndrome in 6, and nonfunctioning adenoma in 7) who underwent transperitoneal laparoscopic adrenalectomy during the same period. The mean size of the adrenal tumors of other pathology was 2.4 cm. In eight of the nine patients with pheochromocytoma, laparoscopic adrenalectomy was successful. The procedure was converted to open surgery in the patient with bilateral tumors because of uncontrollable hemorrhage. A hypertensive crisis with the systolic blood pressure >200 mm Hg occurred in 6 patients (67%), but the episode could be controlled by temporary discontinuation of tumor manipulation, administration of drugs, or both. In adrenalectomy for pheochromocytoma, the mean operative time was longer (199 v 177 minutes) and the mean estimated blood loss was greater (360 v 54 mL) than for tumors of other pathology. Blood transfusion was given to two patients with pheochromocytoma but to no patient with tumors of other pathology. The patients with adrenal tumors of other pathology could resume normal activity earlier (mean 18 v 26 days) than those with pheochromocytoma. The operation is more difficult and the morbidity is higher in laparoscopic adrenalectomy for pheochromocytoma than that for tumors of other pathology. An experienced team of surgeons with advanced laparoscopic skills and anesthesiologists is mandatory. In large tumors, great caution should be taken for intraoperative complications. Nevertheless, laparoscopic adrenalectomy is not contraindicated for pheochromocytoma and can be performed safely.


Genome-Wide Identification, Characterization, and Expression Analysis of the NAC Transcription Factor in Chenopodium quinoa.
The NAC (NAM, ATAF, and CUC) family is one of the largest families of plant-specific transcription factors. It is involved in many plant growth and development processes, as well as abiotic/biotic stress responses. So far, little is known about the NAC family in Chenopodium quinoa. In the present study, a total of 90 NACs were identified in quinoa (named as CqNAC1-CqNAC90) and phylogenetically divided into 14 distinct subfamilies. Different subfamilies showed diversities in gene proportions, exon-intron structures, and motif compositions. In addition, 28 CqNAC duplication events were investigated, and a strong subfamily preference was found during the NAC expansion in quinoa, indicating that the duplication event was not random across NAC subfamilies during quinoa evolution. Moreover, the analysis of Ka/Ks (non-synonymous substitution rate/synonymous substitution rate) ratios suggested that the duplicated CqNACs might have mainly experienced purifying selection pressure with limited functional divergence. Additionally, 11 selected CqNACs showed significant tissue-specific expression patterns, and all the CqNACs were positively regulated in response to salt stress. The result provided evidence for selecting candidate genes for further characterization in tissue/organ specificity and their functional involvement in quinoa's strong salinity tolerance.


Hollow microneedle-based sensor for multiplexed transdermal electrochemical sensing.
The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals suffering from chronic medical conditions facile assessment of their immediate physiological state. Furthermore, it could serve as a research tool for analysis of complex, multifactorial medical conditions. In order for such a multianalyte sensor to be realized, it must be minimally invasive, sampling of interstitial fluid must occur without pain or harm to the user, and analysis must be rapid as well as selective. Initially developed for pain-free drug delivery, microneedles have been used to deliver vaccines and pharmacologic agents (e.g., insulin) through the skin. Since these devices access the interstitial space, microneedles that are integrated with microelectrodes can be used as transdermal electrochemical sensors. Selective detection of glucose, glutamate, lactate, hydrogen peroxide, and ascorbic acid has been demonstrated using integrated microneedle-electrode devices with carbon fibers, modified carbon pastes, and platinum-coated polymer microneedles serving as transducing elements. This microneedle sensor technology has enabled a novel and sophisticated analytical approach for in situ and simultaneous detection of multiple analytes. Multiplexing offers the possibility of monitoring complex microenvironments, which are otherwise difficult to characterize in a rapid and minimally invasive manner. For example, this technology could be utilized for simultaneous monitoring of extracellular levels of, glucose, lactate and pH, which are important metabolic indicators of disease states (e.g., cancer proliferation) and exercise-induced acidosis.


The pathogenesis hypothesis and research progress of CLIPPERS: A literature review.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is still a rare autoimmune disease in the world. In recent years, there are more and more reports about the clinical manifestations of CLIPPERS, but the specific etiology and pathogenesis are not clear. In this paper, by collating the literature reported in recent years, in the reported effective treatment cases, we found the current hypothesis about the pathogenesis of CLIPPERS. Three pathogenesis hypotheses: organ-specific autoimmunity; virus infection affects autoimmunity; and helper T lymphocyte 17 mediates autoimmunity. Although it is hypothetical, it is expected to further clarify the pathogenesis, evolution characteristics, and treatment of CLIPPERS, so as to provide a reference for further understanding of the disease. In the future, more observations and studies are needed to further verify the feasibility of the hypothesis. This article expands on atypical clinical manifestations and summarizes treatment options. Hope to provide a reference for clinical diagnosis and treatment of CLIPPERS.


Protein kinase X activates ureteric bud branching morphogenesis in developing mouse metanephric kidney.
The human protein kinase X (PRKX) gene was identified previously as a cAMP-dependent serine/threonine kinase that is aberrantly expressed in autosomal dominant polycystic disease kidneys and normally expressed in fetal kidneys. The PRKX kinase belongs to a serine/threonine kinase family that is phylogenetically and functionally distinct from classical protein kinase A kinases. Expression of PRKX activates cAMP-dependent renal epithelial cell migration and tubular morphogenesis in cell culture, suggesting that it might regulate branching growth of the collecting duct system in the fetal kidney. With the use of a mouse embryonic kidney organ culture system that recapitulates early kidney development in vitro, it is demonstrated that lentiviral vector-driven expression of a constitutively active, cAMP-independent PRKX in the ureteric bud epithelium stimulates branching morphogenesis and results in a 2.5-fold increase in glomerular number. These results suggest that PRKX stimulates epithelial branching morphogenesis by activating cell migration and support a role for this kinase in the regulation of nephrogenesis and of collecting system development in the fetal kidney.


Renin and atrial natriuretic peptide restriction fragment length polymorphisms: association with ethnicity and blood pressure.
An investigation of restriction fragment length polymorphisms (RFLPs) and association with blood pressure was carried out for the candidate genes coding for renin (REN) and atrial natriuretic peptide (ANP). The relationship between blood pressure, REN and ANP gene RFLPs was tested in a population of black Afro-Caribbean and white European subjects sampled randomly from family practice registers. Upper and lower quintiles for diastolic blood pressure were selected for analysis. Digests of DNA were prepared from leucocytes and RFLPs were determined using Southern blotting analysis with REN and ANP gene probes. There were highly significant ethnic differences found for BglI, Bg/lI and TaqI polymorphisms with 5'REN probe and for BglI polymorphism with an ANP probe. There was also an association between blood pressure and the BglI/REN polymorphism in Afro-Caribbeans but not with any other polymorphisms studied in either ethnic group. The findings show significant ethnic RFLP differences at the gene loci for both renin and ANP and provide evidence for a possible link between variations within or close to the renin gene and elevated blood pressure in Afro-Caribbeans.