Comparisons of food intake between breast cancer patients and controls in Korean women.
The purpose of this study was to compare food intakes between Korean breast cancer patients and a healthy control group. We compared the intake of nutrients of 117 food items between Korean breast cancer patients (n=97) and age matched healthy controls (n=97). Nutrient intake was estimated using a quantitative food frequency questionnaire. The mean caloric intake of breast cancer patients and healthy controls was not significantly different. Breast cancer patients consumed significantly less fat and antioxidant nutrients such as vitamin A, retinol, beta-carotene, vitamin C and vitamin E when compared to the control subjects. Among the food items, the intake of eggs (p<0.01), legumes (p<0.05), vegetables (p<0.05), seasonings (p<0.001), and oils and fats (p<0.01) in breast cancer patients was significantly lower than that in the controls. These results suggest that Korean breast cancer patients consumed less amount of soy and vegetables, which are rich source of antioxidant nutrients and phytosterols. Thus, dietary guidance to increase intake of these foods may be beneficial in the prevention of breast cancer.


Nuclear quantum effects in thermal conductivity from centroid molecular dynamics.
We show that the centroid molecular dynamics (CMD) method provides a realistic way to calculate the thermal diffusivity a = λ/ρcV of a quantum mechanical liquid such as para-hydrogen. Once a has been calculated, the thermal conductivity can be obtained from λ = ρcVa, where ρ is the density of the liquid and cV is the constant-volume heat capacity. The use of this formula requires an accurate quantum mechanical heat capacity cV, which can be obtained from a path integral molecular dynamics simulation. The thermal diffusivity can be calculated either from the decay of the equilibrium density fluctuations in the liquid or by using the Green-Kubo relation to calculate the CMD approximation to λ and then dividing this by the corresponding approximation to ρcV. We show that both approaches give the same results for liquid para-hydrogen and that these results are in good agreement with the experimental measurements of the thermal conductivity over a wide temperature range. In particular, they correctly predict a decrease in the thermal conductivity at low temperatures-an effect that stems from the decrease in the quantum mechanical heat capacity and has eluded previous para-hydrogen simulations. We also show that the method gives equally good agreement with the experimental measurements for the thermal conductivity of normal liquid helium.


Can Simple Interaction Models Explain Sequence-Dependent Effects in Peptide Homodimerization?
The development of rapid methods to explain and predict peptide interactions, aggregation, and self-assembly has become important to understanding amyloid disease pathology, the shelf stability of peptide therapeutics, and the design of novel peptide materials. Although experimental aggregation databases have been used to develop correlative and statistical models, molecular simulations offer atomic-level details that potentially provide greater physical insight and allow one to single out the most explanatory simple models. Here, we outline one such approach using a case study that develops homodimerization models for serine-glycine peptides with various hydrophobic leucine mutations. Using detailed all-atom simulations, we calculate reference dimerization free energy profiles and binding constants for a small peptide library. We then use statistical methods to systematically assess whether simple interaction models, which do not require expensive simulations and free energy calculation, can capture them. Surprisingly, some combinations of a few simple scaling laws well recapitulate the detailed, all-atom results with high accuracy. Specifically, we find that a recently proposed phenomenological hydrophobic force law and coarse measures of entropic effects in binding offer particularly high explanatory power, underscoring the physical relevance to association that these driving forces can play.


Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men.
In a phase I single-centre, open, randomized study, the pharmacokinetics of two doses of a transdermal testosterone gel containing 2.5% testosterone were evaluated in 26 healthy male volunteers. To eliminate the influence of endogenous serum testosterone, gonadotrophins and endogenous testosterone secretion were suppressed by a single intramuscular injection of 400 mg norethisterone enanthate. Fourteen men applied 5.0 g and 12 men applied 2.5 g testosterone gel daily for 10 days. Half the men in each group washed the gel off 10 min after it had been applied. In all the men, a marked suppression of LH, FSH, testosterone, dihydrotestosterone (DHT) and oestradiol was observed after norethisterone treatment. Physiological serum concentrations of testosterone were restored during the 10-day treatment period in the group of men applying 5.0 g testosterone gel. Increasing serum concentrations of testosterone from day 1 to day 10 were observed. Oestradiol and DHT concentrations did not exceed normal values. Washing 10 min after gel application did not influence the resorption of testosterone. A dose of 2.5 g testosterone gel was insufficient to achieve physiological serum concentrations of testosterone. Testosterone replacement treatment with 5.0 g of this 2.5% testosterone gel is able to achieve constant physiological testosterone concentrations in gonadotrophin-suppressed men. Washing the skin after 10 min does not influence the pharmacokinetic profile and thus significantly reduces the risk of contamination of female partners or infants.


Redox features of the cell: a gender perspective.
Reactive oxygen and nitrogen species have been implicated in diverse subcellular activities, including cell proliferation,differentiation and, in some instances, cell injury and death. The implications of reactive species inhuman pathology have also been studied in detail. However, although the role of free radicals in the pathogenesis of human diseases has been extensively analyzed in different systems (i.e., in vitro, ex vivo, and in vivo),it is still far from elucidated. In particular, the possible role of gender 4 differences in human pathophysiology associated with reactive species is a promising new field of investigation. Although the complex scenario this presents is still incomplete, important gender-associated "redox features" of cells have already been described in the literature. Here we summarize the different aspects of redox-associated molecules and enzymes in regard to gender differences in terms of the intracellular production and biochemical activity of reactive species. These are often associated with the pathogenetic mechanisms underlying several human morbidities(e.g., degenerative diseases) and can represent a specific target for new pharmacologic strategies. Gender differences may thus pose an important challenge for future studies aimed at the clinical management of diseases characterized by a redox imbalance.


Functional precursors to language and its lateralization.
An adequate account of language evolution must reconcile the propositions that language is unique but has precursors. The paper of Bellman and Goldberg and that of Tzeng and Wang each neglects one of these propositions. We suggest that the uniqueness of language lies primarily in its dualistic structure which has a frame-content mode of organization: at the phonological level, consonant and vowel elements are inserted into syllabic frames; and at the morphological level, stem forms of content words are inserted into syntactic frames. We suggest that the morphological level evolved from the phonological level and that the frame-content mode of organization in phonology had a precursor in the form of bimanual coordination in which the nonpreferred (frame) hand holds an object operated on by the preferred hand (content). It is argued that lateralization of cortical function evolved first for bimanual coordination, then for language. Old World monkey hand preferences may be consistent with both the putative left-hemisphere specialization for bimanual coordination and the human right-hemisphere specialization for spatial functions.


[Primary and bilateral non-Hodgkin's lymphoma of the adrenal gland (a case report and literature review)].
Primary non-Hodgkin's lymphoma of the adrenal gland is rare. We report the case of a 31-years-old patient hospitalized with asthenia and adrenal insufficiency. The CT scan showed a bilateral adrenal mass. A scano-guided biopsy suspected an endocrinoid tumor. The surgical exploration demonstrated a huge mass invading the retroperitoneal space, and the biopsy concluded to a central follicular phenotype B rmalignant lymphoma with a high rank of malignity. The thoracic CT scan did not show any lymph node. The medullar biopsy eliminated a secondary lymphoma. The patient was treated by chemotherapy and radiotherapy with a good result during 16 months.


[Restriction of movement in the proximal and distal radio-ulnar joints in posttraumatic angulation and torsion of the radius].
Posttraumatic angular and rotatory deformities of radius or ulna or both frequently cause a restriction of supination-pronation. The loss of motion is determined by the direction and the degree of angulation and by location of fracture. The dorsopalmar angulation and radioulnar deviation of the radius in an anatomic forearm specimen are simulated and the motions of the radius during supination-pronation are investigated. Dorsal angulation and radial deviation produce a considerable loss of pronation. However, supination losses are much less affected. The reduction of the interosseous gap is an important morphological reason of this effect. The angle of torsion is measured in left and right intact radii between transversal epiphyseal and diaphyseal axes. The torsion of the distal radial epiphysis varies from 0 to 16 degrees. Left and right radius of a single individual show very small differences in their torsion; therefore a comparison to the intact contralateral bone is indicated.


Angular distribution of photoelectrons in small molecules: a molecular quantum defect calculation.
The molecular quantum defect orbital (MQDO) method, previously used in the determination of molecular photoionization cross sections, is applied here to calculate the angular distribution of photoelectrons arising from the molecular photoionization. Calculations are performed for the ionization from outer valence orbitals of HF, H(2)O, NH(3), N(2)O, and H(2)CO molecules. The results are compared with previous measurements and with theoretical curves found in the literature. Profiles of the angular distribution parameter as a function of photoelectron energy covering a range from the photoionization threshold to 120 eV are presented for the above molecules. The energy dependence of the angular distributions predicted by the MQDO calculations agrees fairly well with predictions from more sophisticated theories and with observed results.


Digital PCR as a tool to measure HIV persistence.
Although antiretroviral therapy is able to suppress HIV replication in infected patients, the virus persists and rebounds when treatment is stopped. In order to find a cure that can eradicate the latent reservoir, one must be able to quantify the persisting virus. Traditionally, HIV persistence studies have used real-time PCR (qPCR) to measure the viral reservoir represented by HIV DNA and RNA. Most recently, digital PCR is gaining popularity as a novel approach to nucleic acid quantification as it allows for absolute target quantification. Various commercial digital PCR platforms are nowadays available that implement the principle of digital PCR, of which Bio-Rad's QX200 ddPCR is currently the most used platform in HIV research. Quantification of HIV by digital PCR is proving to be a valuable improvement over qPCR as it is argued to have a higher robustness to mismatches between the primers-probe set and heterogeneous HIV, and forfeits the need for a standard curve, both of which are known to complicate reliable quantification. However, currently available digital PCR platforms occasionally struggle with unexplained false-positive partitions, and reliable segregation between positive and negative droplets remains disputed. Future developments and advancements of the digital PCR technology are promising to aid in the accurate quantification and characterization of the persistent HIV reservoir.


Factors affecting surgery decision-making in patients with a chronic neurovascular condition.
To explore the factors that affect patient decision-making for an elective surgery. Cerebral cavernous malformations are lesions found in the brain and spinal cord comprised of abnormal blood vessels, which bleed sporadically causing serious neurological deficits. Course of treatment for cerebral cavernous malformation is often ultimately left up to the patient, and can include symptom management or surgery. Decision-making for surgery in life-threatening conditions has been well documented in the literature. Less extensive research has focused on elective surgeries, where patients have a choice. There has been no research on the factors that affect decision-making for cavernous malformation patients. Correlational self-report survey. In part of a larger online study, participants were asked to rate the importance of six factors on their decision-making about surgery for cavernous malformation. Factors that were rated most important for individuals' decision-making included doctor's opinion regarding surgery, presence of disabling symptoms, fear of symptoms getting worse or developing new symptoms, and availability of an expert surgeon. Results indicated that these were rated as more important than having social support during recovery or having the means to pay for surgery. Additionally, having social support during recovery was rated as significantly more important than having the means to pay for surgery. Factors that affect decision-making for patients diagnosed with cavernous malformation were similar to those found with other medical conditions requiring elective surgery. This study will assist healthcare workers in understanding the decision-making process of individuals who may choose an elective surgery for potentially disabling conditions with uncertain outcomes. Understanding the complex factors that affect decision-making in cavernous malformation will assist healthcare professionals to better communicate and support patients in their elective surgery decision-making.


Systematic variation in the temperature dependence of bacterial carbon use efficiency.
Carbon use efficiency (CUE) is a key characteristic of microbial physiology and underlies community-level responses to changing environments. Yet, we currently lack general empirical insights into variation in microbial CUE at the level of individual taxa. Here, through experiments with 29 strains of environmentally isolated bacteria, we find that bacterial CUE typically responds either positively to temperature, or has no discernible response, within biologically meaningful temperature ranges. Using a global data synthesis, we show that these results are generalisable across most culturable groups of bacteria. This variation in the thermal responses of bacterial CUE is taxonomically structured, and stems from the fact that relative to respiration rates, bacterial population growth rates typically respond more strongly to temperature, and are also subject to weaker evolutionary constraints. Our results provide new insights into microbial physiology, and a basis for more accurately modelling the effects of thermal fluctuations on complex microbial communities.


Can we predict perceived risk?
This paper examines the possibility that we may be able to use subjective measures of perceived risk in order to assess the relative safety of different shift systems. A large-scale survey of safety-critical engineers included three items relating to risk on each shift, namely alertness, likelihood of making a mistake and confidence in driving home after it. These three measures were found to load on a separate factor for each shift. Hierarchical regression analyses indicated that perceived night shift risk could be predicted on the basis of circadian type, the extent to which the engineers could control their work schedule, and a number of features of the scheduled shift system. In most cases the relationships observed were reasonably consistent with established trends in either performance capability or accident and injury frequency. However, there were exceptions to this indicating that results based on measures of perceived risk should be interpreted with the utmost caution.


[Pre-transplantation evaluation with echo-Doppler of the receptor's vascular risk factors].
A total of 51 potential recipients of a renal transplant (RT) have been evaluated with an Eco-Doppler study of the posterior femoral, popliteal and posterior tibial corteries. Acceleration (AC), mean rate (MR), maximum systolic rate (MXSR) and minimal diastolic rate (MNDR), as well as pulsatility (PI) and resistance index (RI) were measured. Arterial high blood pressure (HBP), smoking, time in haemodialysis (HD) and cholesterol and triglycerides levels, were evaluated as vascular risk factors. RI and PI were maximal, and MXSR, MR and AC minimal at the popliteal artery level. Smoking (number of cigarettes/day) (R = 0.77), systolic blood pressure (BP) (R = 0.43), time of HBP evolution (R = 0.044), cholesterol level (R = 0.43) and time in HD (R = 0.35) correlate with Eco-Doppler parameters. Fifteen of these 51 patients underwent transplantation, and increased RR and PR with decreased MR and MXSR were seen post-RT in the ipsilateral popliteal and posterior tibial arteries. Eco-Doppler is a useful technique to evaluate the vascular risk of potential RT recipients.


Identification of Alzheimer and vascular lesion thresholds for mixed dementia.
To explore the pathological substrates of mixed dementia, we performed a detailed analysis of lacunar and microvascular pathology in 156 autopsied, elderly individuals with various degrees of Alzheimer's disease (AD) pathology. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Braak neurofibrillary tangle (NFT) and Ass-protein deposition staging and bilateral semi-quantitative assessment of microvascular ischaemic pathology and lacunes; statistics included univariate and multiple regression models controlling for age, and receiver-operating characteristic analysis. Sensitivity analysis was performed in a randomized derivation sub-sample and tested in a validation sub-sample. White matter lacunes, periventricular and diffuse white matter demyelination and focal and diffuse cortical gliosis were not associated with cognition. Braak NFT, Ass deposition, cortical microinfarcts (CMI) and thalamic and basal ganglia lacunes (TBGL) predicted 27% of CDR variability and 49% of the presence of dementia. Braak NFT, CMI and TBGL thresholds determined in a derivation sample yielded 0.88 sensitivity, 0.79 specificity and 0.85 correct classification rate for dementia in a validation sample. The same thresholds distinguished three groups of demented cases consistent with mixed dementia, pure vascular dementia and AD. These findings indicate that the clinical expression of the vascular component in mixed cases is highly dependent on lesion type and location as well as severity of concomitant AD-related pathology. Proposed thresholds for vascular and degenerative lesions predict the presence of dementia with great accuracy and provide a basis for distinguishing pure vascular dementia or AD from mixed cases.


Degenerative changes of discs and facet joints in lumbar total disc replacement using ProDisc II: minimum two-year follow-up.
A retrospective clinical and radiologic data analysis. To determine the radiologic changes in the discs at the adjacent levels and facets at the index and adjacent levels after total disc replacement (TDR) using ProDisc II in a minimum 2-year follow-up. The main purposes of TDR are to preserve the physiologic segmental motion at index level, and to prevent accelerated degeneration at the index and adjacent segments. However, there are few reports dealing with the effects of TDR on the degenerative changes in a long-term follow-up. After TDR using ProDisc II, the degree of disc and facets degeneration at the index and adjacent levels was assessed by observing lumbar magnetic resonance imaging (MRI) and computed tomography (CT) images before surgery and at minimum 26 months after operations. The degenerative changes of the discs and facets were determined in relation to the clinical outcome, various perioperative factors, and prosthesis factors. Thirty-two patients with 41 TDR included in this investigation. The progression of facets degeneration (PFA) was observed in 12 of 41 TDR levels. Among 47 adjacent segments, the progression of disc degeneration and PFA were observed in 2 levels (4.3%), and 3 levels (6.4%), respectively. All cases of PFA occurred only in those with preoperative degeneration of grade 1. PFA at the index segments was positively related with female in gender (P = 0.008), the malposition of prosthesis on frontal plane (P = 0.025), and 2-level TDR in the number of TDR level (P = 0.008). After TDR using ProDisc II, the degenerative changes in the discs and facets at the adjacent segments appeared to be minimal. However, in 29.3% of the TDR segments, the facet joints presented PFA, which was more common in female, malposition of prosthesis on frontal plane, and 2-level TDR in a minimum 2-year follow-up.


The subjective experience of pain: where expectations become reality.
Our subjective sensory experiences are thought to be heavily shaped by interactions between expectations and incoming sensory information. However, the neural mechanisms supporting these interactions remain poorly understood. By using combined psychophysical and functional MRI techniques, brain activation related to the intensity of expected pain and experienced pain was characterized. As the magnitude of expected pain increased, activation increased in the thalamus, insula, prefrontal cortex, anterior cingulate cortex (ACC) and other brain regions. Pain-intensity-related brain activation was identified in a widely distributed set of brain regions but overlapped partially with expectation-related activation in regions, including the anterior insula and ACC. When expected pain was manipulated, expectations of decreased pain powerfully reduced both the subjective experience of pain and activation of pain-related brain regions, such as the primary somatosensory cortex, insular cortex, and ACC. These results confirm that a mental representation of an impending sensory event can significantly shape neural processes that underlie the formulation of the actual sensory experience and provide insight as to how positive expectations diminish the severity of chronic disease states.


Sonoelastography in the evaluation of capsule formation after breast augmentation - preliminary results from a follow-up study.
There are many indications for breast augmentation, including reconstruction after mastectomy, correction of congenital disorders and cosmetic procedures. The most frequent local complication of this surgery is capsule formation due to fibrosis. The aim of the study was to assess the usefulness of sonoelastography in the evaluation of capsule formation around silicone implants. The study group included 13 patients aged 20 to 41, who underwent breast augmentation with silicone implants. Their 26 breasts were examined before surgery, 7 and 14 days and a minimum of 8.5 months after surgery. The breast stiffness was assessed with tonometry and shear wave elastography to evaluate elasticity of the breast tissue and capsule formation after surgery. We assessed the correlation between capsular elasticity measured at successive visits and the Baker scale. There were no significant relationships between any pairs of variables (p > 0.05). We also analyzed the correlation between the time of the follow-up and changes in the tissue elasticity of every region - no significant relationship was found. The greatest decrease in pericapsular elasticity was established in lower and inner quadrants. Moreover, there was a significant difference between the elasticity of the tissue before and 1 week after surgery (p < 0.05) and no significant changes in the elasticity before surgery and at the end of the follow-up. Sonoelastography is precise in evaluation of capsule formation after breast augmentation. It may show changes that cannot be assessed using palpation.


Local ubiquitin-proteasome-mediated proteolysis and long-term synaptic plasticity.
The ubiquitin-proteasome pathway (UPP) of protein degradation has many roles in synaptic plasticity that underlies memory. Work on both invertebrate and vertebrate model systems has shown that the UPP regulates numerous substrates critical for synaptic plasticity. Initial research took a global view of ubiquitin-protein degradation in neurons. Subsequently, the idea of local protein degradation was proposed a decade ago. In this review, we focus on the functions of the UPP in long-term synaptic plasticity and discuss the accumulated evidence in support of the idea that the components of the UPP often have disparate local roles in different neuronal compartments rather than a single cell-wide function.


Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig.
Ethanol stimulating transient receptor potential vanilloid 1 (TRPV1) on primary sensory neurons promotes neurogenic inflammation, including calcitonin gene-related peptide (CGRP)-mediated coronary dilation. Alcoholic beverages trigger migraine attacks and activation of trigeminal neurons plays a role in migraine. We have investigated in guinea pigs whether ethanol by TRPV1 stimulation causes neurogenic inflammation in the trigeminovascular system. Ethanol-evoked release of neuropeptides from slices of dura mater was abolished by Ca(2+) removal, capsaicin pretreatment and the TRPV1 antagonist, capsazepine. Intragastric ethanol increased plasma extravasation in dura mater, an effect abolished by capsazepine and the NK1 receptor antagonist, SR140333, and caused vasodilation around the middle meningeal artery, an effect abolished by capsazepine and the CGRP receptor antagonist, BIBN4096BS. Vasodilation of meningeal vessels by TRPV1 activation and CGRP release may be relevant to the mechanism by which alcohol ingestion triggers migraine attacks.


Characterization of lentiviral vector production using microwell suspension cultures of HEK293T-derived producer cells.
ProSavin(®) is a lentiviral vector (LV)-based gene therapy for Parkinson's disease. ProSavin(®) is currently in a Phase I/II clinical trial using material that was generated by transient transfection of adherent human embryonic kidney (HEK)293T cells. For future large-scale productions of ProSavin(®), we have previously reported the development and characterization of two inducible producer cell lines, termed PS5.8 and PS46.2. PS46.2 has been successfully adapted to grow in suspension cultures. The present study describes the creation of a small-scale (<2 ml) microwell-based experimental platform for the parallel investigation of ProSavin(®) production using suspension-adapted PS46.2. This is combined with statistical design of experiments (DoE) techniques to enable rapid characterization of the process conditions that impact cell growth and LV production. The effects of postinduction period, microwell liquid fill volume, and concentration of inducer (doxycycline) on ProSavin(®) titer and the particle:infectivity (P:I) ratio was investigated using three rounds of DoE, in order to identify appropriate factor ranges and optimize production conditions. We identified an optimal "harvest window" between approximately 26-46 hr within which maximal titers of around 6×10(4) transducing units (TU)/ml were obtained (an approximately 30-fold improvement compared to starting microwell conditions), providing that the fill volume was maintained at or below 1 ml and the doxycycline concentration was at least 1.0 μg/ml. Insights from the microwell studies were subsequently used to rapidly establish operating conditions for ProSavin(®) production in a 0.5-L wave bioreactor culture. The information presented herein thus aids the design and evaluation of scalable production processes for LVs.


Regional differences in treatment frequency and case-fatality rates in korean patients with acute myocardial infarction using the Korea national health insurance claims database: findings of a large retrospective cohort study.
Issues regarding healthcare disparity continue to increase in connection with access to quality care for acute myocardial infarction (AMI), even though the case-fatality rate (CFR) continues to decrease. We explored regional variation in AMI CFRs and examined whether the variation was due to disparities in access to quality medical services for AMI patients. A dataset was constructed from the Korea National Health Insurance Claims Database to conduct a retrospective cohort study of 95,616 patients who were admitted to a hospital in Korea from 2003 to 2007 with AMI. Each patient was followed in the claims database for information about treatment after admission or death. The procedure rate decreased as the region went "down" from Seoul to the county level, whereas the AMI CFR increased as the county level as a function of proximity to the county level (30-day AMI CFRs: Seoul, 16.4%; metropolitan areas, 16.2%, cities; 18.8%, counties, 39.4%). Even after adjusting for covariates, an identical regional variation in the odds of patients receiving treatment services and dying was identified. After adjusting for invasive and medical management variables in addition to earlier covariates, the death risk in the counties remained statistically significantly higher than in Seoul; however, the degree of the difference decreased greatly and the significant differences in metropolitan areas and cities disappeared. Policy interventions are needed to increase access to quality AMI care in county-level local areas because regional differences in the AMI CFR are likely caused by differences in the performance of medical and invasive management among the regions of Korea. Additionally, a public education program to increase the awareness of early symptoms and the necessity of visiting the hospital early should be established as the first priority to improve the outcome of AMI patents, especially in county-level local areas.


Bisphosphonate therapy associated with bilateral atypical femoral fracture and delayed union.
The aim of this study was to identify the risk factors for developing atypical femoral fractures (AFF) and to examine the effect of bisphosphonate (BP) therapy on delayed bone union and bilateral fractures. Between January 1st, 2012 and December 31st, 2020, a total of 74 AFF patients (8 males, 66 females; mean age: 75.4±7.2 years; range, 51 to 94 years) were recorded in two centers and retrospectively analyzed. A control fragility fracture group (n=143) was compared to the AFF group according to fracture characteristics, surgical fixation methods, comorbidities, and medications. The AFF patients were selected and subdivided according to their BP therapy: Group 1 (without BP) and Group 2 (with BP). Group 2 was further classified into Group 2a (<5 years of BP) and Group 2b (<5 years of BP). The multivariate logistic regression model showed that, BP drug use was the most significant risk factor in development of AFF (p<0.001, odds ratio= 10.749, 95% confidence interval: 3.886-29.733). The patients on BP showed longer bone union (Group 2 - 8.3±3.5 vs. Group 1 - 6.4±3.1 months, p=0.02; Group 2b - 9±3.8 vs. Group 2a - 7.3 ±3.9 months, p=0.09). Of all 19 cases of bilateral fractures, 14 were in Group 2 with BP use (p=0.11). Of 74 cases, 26 (35%) contralateral femoral X-rays were taken on admission and 24 (92%) showed AFF minor criteria signs. Of these 24 patients, 10 (42%) developed contralateral AFF. The most significant risk factor in development of AFF was BP drug use. Longer BP therapy (>5 years) showed longer delayed bone union, which was not significant. There was a relatively high risk of developing AFFs and bilateral fractures on BP therapy. In case of an AFF, a contralateral femoral X-ray must be always performed for signs of an impending fracture.


Lipid-Based Liquid Crystalline Nanoparticles Facilitate Cytosolic Delivery of siRNA via Structural Transformation.
RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform thestructure in the intracellular acidic environment and perform high-efficient siRNA delivery for cancer treatment. The developed nano-Transformers have satisfactory siRNA loading efficiency and low cytotoxicity. Different from the traditional cationic nanocarriers, the endosomal membrane fusion induced by the conformational transition of lipids contributes to the easy dissociation of siRNA from nanocarriers and direct release of free siRNA into cytoplasm. We show that transfection with cyclin-dependent kinase 1 (CDK1)-siRNA-loaded nano-Transformers causes up to 95% reduction of relevant mRNA in vitro and greatly inhibits the tumor growth without causing any immunogenic response in vivo. This work highlights that the lipid-based nano-Transformers may become the next generation of siRNA delivery system with higher efficacy and improved safety profiles.


Johanson-Blizzard syndrome with associated urogenital anomalies.
We present a case of a child with pancreatic insufficiency and facial defects typical of Johanson-Blizzard syndrome (JBS), along with the more facultative anomalies of the JBS, such as those of the urogenital system including persistent urogenital sinus, urethral duplication and dysplastic kidneys. Fetal ultrasound in a 21-year-old G1P1 woman revealed ambiguous genitalia. Examination at birth revealed a phallic structure with urethral meatus, non-palpable gonads, two orifices in close proximity in the perineum, with the anterior being a common urogenital channel and the posterior, the rectum. A voiding cystourethrogram/genitogram showed bilateral high-grade vesicoureteral reflux and a common urogenital sinus extending 1.5 cm before dividing into three channels: the native urethra, an accessory urethra directed anteriorly towards the clitoris and a septate vagina with uterus didelphys. JBS was suspected by clinical presentation and confirmed by UBR1 molecular testing (46,XX). At 16 months of age, she underwent feminising genitoplasty and posterior sagittal anorectoplasty.


Predictors of Daily Mobility of Adults in Peri-Urban South India.
Daily mobility, an important aspect of environmental exposures and health behavior, has mainly been investigated in high-income countries. We aimed to identify the main dimensions of mobility and investigate their individual, contextual, and external predictors among men and women living in a peri-urban area of South India. We used 192 global positioning system (GPS)-recorded mobility tracks from 47 participants (24 women, 23 men) from the Cardiovascular Health effects of Air pollution in Telangana, India (CHAI) project (mean: 4.1 days/person). The mean age was 44 (standard deviation: 14) years. Half of the population was illiterate and 55% was in unskilled manual employment, mostly agriculture-related. Sex was the largest determinant of mobility. During daytime, time spent at home averaged 13.4 (3.7) h for women and 9.4 (4.2) h for men. Women's activity spaces were smaller and more circular than men's. A principal component analysis identified three main mobility dimensions related to the size of the activity space, the mobility in/around the residence, and mobility inside the village, explaining 86% (women) and 61% (men) of the total variability in mobility. Age, socioeconomic status, and urbanicity were associated with all three dimensions. Our results have multiple potential applications for improved assessment of environmental exposures and their effects on health.


Success rate in implant-supported overdenture and implant-supported fixed denture in cleft lip and palate patients.
The prosthetic treatment in cleft patients is challenging. Based on this, the aim of this study was to evaluate the longevity of prosthetic rehabilitation treatment with implant-supported overdenture (IOD) and implant-supported fixed denture (IFD) in cleft lip and palate patients in a period of 22 years. The medical records of 72 patients were analyzed (29 males and 43 females), and the survival rate of the implants was evaluated. Moreover, the prostheses' time of use and the reason for the changing of these were also evaluated. Four-hundred-seventeen implants were installed, and 370 implants survive today. The mean survival time of the implants was 7.6 years. Regarding the 97 prostheses made, the time of average use was 3.28 for the IFDs and 3.92 for IODs. The reasons for the replacements of the prostheses were mainly: fracture of the acrylic base (29.6%) and loss of vertical dimension of occlusion (VDO) (18.5%) in the IFDs. Moreover, in IODs, these were accounted for the loss of VDO due to teeth damage (17.2%) and implant loss (14.6%). The maintenance of the prostheses was challenging because the patients had difficulties returning for periodic control, but this fact did not result in the decrease of the success rate of the implants. The longevity of implants and prostheses was satisfactory; however, the prostheses showed repetitions mainly due to the wear of the teeth, with decreased vertical dimension and fracture of acrylic base.


Prophylaxis with Isavuconazole or Posaconazole Protects Immunosuppressed Mice from Pulmonary Mucormycosis.
We assessed prophylactic or continuous therapy of isavuconazole, posaconazole, or voriconazole in treating pulmonary murine mucormycosis. In the prophylaxis studies, only isavuconazole treatment resulted in significantly improved survival and lowered tissue fungal burden of immunosuppressed mice infected with Rhizopus delemar. In the continuous treatment studies, isavuconazole and posaconazole, but not voriconazole, equally prolonged survival time and lowered tissue fungal burden compared to placebo-treated mice. These results support the use of isavuconazole and posaconazole in prophylaxis treatment.


Mechanical heterogeneity in ionic liquids.
Molecular dynamics (MD) simulations of five ionic liquids based on 1-alkyl-3-methylimidazolium cations, [C n C1im]+, have been performed in order to calculate high-frequency elastic moduli and to evaluate heterogeneity of local elastic moduli. The MD simulations of [C n C1im][NO3], n = 2, 4, 6, and 8, assessed the effect of domain segregation when the alkyl chain length increases, and [C8C1im][PF6] assessed the effect of strength of anion-cation interaction. Dispersion curves of excitation energies of longitudinal and transverse acoustic, LA and TA, modes were obtained from time correlation functions of mass currents at different wavevectors. High-frequency sound velocity of LA modes depends on the alkyl chain length, but sound velocity for TA modes does not. High-frequency bulk and shear moduli, K ∞ and G ∞ , depend on the alkyl chain length because of a density effect. Both K ∞ and G ∞ are strongly dependent on the anion. The calculation of local bulk and shear moduli was accomplished by performing bulk and shear deformations of the systems cooled to 0 K. The simulations showed a clear connection between structural and elastic modulus heterogeneities. The development of nano-heterogeneous structure with increasing length of the alkyl chain in [C n C1im][NO3] implies lower values for local bulk and shear moduli in the non-polar domains. The mean value and the standard deviations of distributions of local elastic moduli decrease when [NO3]- is replaced by the less coordinating [PF6]- anion.


The patient and family adjustment to chronic disease in the home.
The increase in chronic disease with shortened hospitalizations has led to an increase in home care, with added adjustment problems for patients and their families. The majority of families cope satisfactorily, although most have periods of instability or difficulties which require appropriate support. In considering the impact of chronic illness, cognizance must be taken of the patient, the illness, the caregiving system, the medical care system, the interrelationship between them and the effect of the environment on all of them. The adjustment to chronic illness depends on the complementary meshing of the life and time cycles of the above factors during the alternating periods of crises and chronic maintenance. It is apparent that, in a pluralistic multicultural society, a broad range of diverse family forms and functioning is compatible with adjustment to a member with chronic disease. Finally, a scheme for the medical team's assessment and care is presented.


Usefulness of computerized tomography in evaluating necrotizing fasciitis.
A 54-year-old man was seen with what appeared to be cellulitis of the left lower extremity. Roentgenograms showed no evidence of gas in soft tissues. Two days later films revealed gas in soft tissues of the leg, but not in the thigh. Computerized tomography showed pockets of gas in the lateral fascial planes of both leg and thigh. Surgical exploration revealed extensive necrotizing fasciitis. CT scanning provided a much more accurate picture of the extent of infection than did standard radiographs.


Performance analysis of EuroSCORE II compared to the original logistic EuroSCORE and STS scores for predicting 30-day mortality after transcatheter aortic valve replacement.
The original European System for Cardiac Operative Risk Evaluation (EuroSCORE) has been recently updated as EuroSCORE II to optimize its efficacy in cardiac surgery, but its performance has been poorly evaluated for predicting 30-day mortality in patients who undergo transcatheter aortic valve replacement (TAVR). Consecutive patients (n = 250) treated with TAVR were included in this analysis. Transapical access was used in 60 patients, while 190 procedures were performed using a transfemoral approach. Calibration (risk-adjusted mortality ratio) and discrimination (C-statistic and U-statistic) were calculated for the logistic EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons (STS) scores for predicting 30-day mortality. Observed mortality was 7.6% in the overall population (6.3% and 11.7% for the transfemoral and transapical cohorts, respectively). Predicted mortality was 22.6 ± 12.8% by logistic EuroSCORE, 7.7 ± 5.8% by EuroSCORE II, and 7.3 ± 4.1% by STS score. The risk-adjusted mortality ratio was 0.34 (95% confidence interval [CI] 0.10 to 0.58) for logistic EuroSCORE, 0.99 (95% CI 0.29 to 1.69) for EuroSCORE II, and 1.05 (95% CI 0.30 to 1.79) for STS score. Moderate discrimination was observed with EuroSCORE II (C-index 0.66, 95% CI 0.52 to 0.79, p = 0.02) compared to the logistic EuroSCORE (C-index 0.63, 95% CI 0.51 to 0.76, p = 0.06) and STS (C-index 0.58, 95% CI 0.43 to 0.73, p = 0.23) score, without a significant difference among the 3 risk scores. Discrimination was slightly better in the transfemoral cohort compared to the transapical cohort with the 3 risk scores. In conclusion, EuroSCORE II and the STS score are better calibrated than the logistic EuroSCORE but have moderate discrimination for predicting 30-day mortality after TAVR.


Influence of the needle bore size on platelet count and routine coagulation testing.
The phlebotomy technique, particularly the use of small-bore needles, may influence the reliability of coagulation testing and platelet count. Routine coagulation tests were assayed in blood specimens collected from 22 consecutive patients in three separate, sequential phlebotomies, using butterfly devices with different needle sizes. Test results of samples collected with 23 and 25 G needles were compared with those obtained with the currently recommended 21 G needle. Although both the prothrombin time and activated partial thromboplastin time displayed a trend towards lower values employing the smaller 23 and 25 G needles, results did not differ significantly from the reference 21 G needle specimen, with the exceptions of D-dimer (25 G versus 21 G needle, 186 +/- 70 versus 178 +/- 66/ml, P < 0.01) and platelet count (23 G versus 21 G needle, 246 +/- 55 versus 254 +/- 56 x 10(-3)/l, P < 0.01; 25 G versus 21 G needle, 240 +/- 55 versus 254 +/- 56 x 10(-3)/l, P < 0.01). None of the mean biases recorded for the parameters was clinically meaningful, nor did they exceed the current desirable analytical quality specifications for desirable bias. Results of the present investigation suggest that, when a proper technique is used and within certain limitations, butterfly devices with small-bore needles may be a reliable alternative to draw venous blood for platelet count and coagulation testing.


Endoplasmic Reticulum-Plasma Membrane Contact Sites.
The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including the plasma membrane (PM). A number of protein tethers that mediate these contacts have been identified, and study of these protein tethers has revealed a multiplicity of roles in cell physiology, including regulation of intracellular Ca2+ dynamics and signaling as well as control of lipid traffic and homeostasis. In this review, we discuss the cross talk between the ER and the PM mediated by direct contacts. We review factors that tether the two membranes, their properties, and their dynamics in response to the functional state of the cell. We focus in particular on the role of ER-PM contacts in nonvesicular lipid transport between the two bilayers mediated by lipid transfer proteins.


Joint attention and disorganized attachment status in infants at risk.
The development of joint attention skills is a major milestone of infancy. Recent research suggests that the development of these skills may be affected by disorganized (D) attachment. This hypothesis was examined in a longitudinal study of attachment and joint attention skill development in a sample of infants at risk for developmental-behavioral morbidity. The results revealed that toddlers with D classifications initiated joint attention with an experimenter significantly less often than did secure, or even other insecure, toddlers. However, no group differences in the capacity to respond to the joint attention bids of others were observed in this study. These data suggest that a disturbance in the tendency to initiate episodes of joint attention with others may be indicative of early social-cognitive and social-emotional disturbance among infants affected by disorganized attachment status. Theory and research is reviewed to suggest that an early impairment in joint attention facility may make a significant contribution to risk for negative cognitive and emotional outcomes among these infants.


Influence of kitesurf equipment on injury rates.
Various injuries in kitesurfing (KS) have been reported so far. The aim of this study was to validate the effect of different kite designs and safety equipment on the injury rate compared to older studies. A retrospective epidemiological study based on an anonymous face-to-face survey was conducted amongst active kitesurfers. The questionnaire consisted of 66 questions focusing on the equipment used, injury rates, overuse injuries and gender differences. A stepwise Poisson-Model was used to identify injury-associated factors. A total of 202 kitesurfers with a mean age of 31.8±9.1 years and 698.2±931.5 hours of KS experience were included. 2613 injuries were recorded (18.5/1000 hours KS). Almost 50% were hematomas, bruises or cuts. 3.9% of all injuries (0.71/1000 hours KS) were time-loss injuries of more than one week. Female kitesurfers had a significantly greater injury rate, were less experienced and fewer of them used C-kites. Height, weight, primary kite spot, experience, physical activity, warm-up/stretching, the type of kite and control bar used, and the use of a board leash were independent factors associated to injury rate. The lower extremity, the elbow, thorax and abdomen were at risk for overuse injuries. An influence of equipment on injuries could be statistically shown. The overall injury rate in KS did not decline in the last decades, but time-loss injuries did.


Endoscopic ureteroneocystostomy: palliative urinary diversion in advanced prostatic cancer.
Distal ureteral obstruction is a common complication in advanced prostatic cancer, secondary to direct compression at the ureterovesical junction and/or invasion of the ureteral orifice and/or of the intramural ureter by the tumor. The ureteral orifice may not be readily visible to the trigone-infiltrating tumor, but remains superficial as it is pushed upward by the tumoral tissue. The indications for palliative diversion in patients with pelvic malignant disease and renal failure from ureteral obstruction remain controversial. We present the results of our endoscopic ureteroneocystostomy technique by which the trigone is resected to restore continuity of the ureteral orifice and to place a double pigtail ureteral stent. Of the 31 operations performed for obstructive prostate cancer, continuity was restored in 76% of cases. Length of hospital stay was gradually reduced to a few days. Median survival after surgery was 8 months (0.25 to 27.5 months). Palliative diversion may be considered a reasonable option for many patients, even in the case of an apparently unpassable obstruction of the pelvic ureter, thereby prolonging survival and improving quality of life.


[Effect of saponin from Tribulus terrestris on hyperlipidemia].
The preventive and therapeutic effects of saponin from Tribulus terrestris L. on diet-induced hyperlipidemia in mice have been studied. It showed that in preventive experiment the saponin could significantly low the levels of serum TC (P < 0.05), LDL-c (P < 0.01) and liver TC (P < 0.05), TG (P < 0.05), and increase the activities of superoxide-dismutase (SOD) in liver. The therapeutic experiment showed that the saponin could significantly reduce the contents of serum TC (P < 0.05) and liver TC (P < 0.01).


Unilateral spiny hyperkeratosis: case report and review of the literature.
We describe the first case of unilateral spiny hyperkeratosis (SH) of the left hand, review the literature and discuss possible patho- mechanisms. SH can be sporadic or familial, often appearing in healthy individuals. However, there is an association with various malignancies in a significant number of the sporadic cases. Although there is no satisfactory explanation of this association, we agree with previous authors that a patient with SH appearing in adult life should be evaluated and followed for the presence of malignancy. Other patients with SH may suffer from a variety of nonmalignant diseases, which may be coincidental or causally related. SH is not a premalignant lesion of the skin and should not be confused with porokeratosis which has a malignant potential. Except for excision of individual lesions, there is no permanent cure.


Reduced Cell Division Control Protein 42 Activity Compromises Hematopoiesis-Supportive Function of Fanconi Anemia Mesenchymal Stromal Cells.
Hematopoietic stem cells preserve their ability to self-renew and differentiate to different lineages in the bone marrow (BM) niche, which is composed in large part by BM stromal cells. Studies have shown that altered signaling in the BM niche results in leukemia initiation or progression. Fanconi anemia (FA) is an inherited BM failure syndrome associated with extremely high risk of leukemic transformation. By using two FA mouse models, here we have investigated the hematopoiesis-supportive function of FA BM mesenchymal stroma cells (MSCs). We found that MSCs deficient for Fanca or Fancc gene are defective in proliferation and prone to undergo senescence in vitro. Mechanistically, we show that the activity of cell division control protein 42 (Cdc42), a Rho GTPase known to be a critical regulator for cytoskeleton organization, is significantly reduced in FA MSCs. Furthermore, we demonstrate that this reduction in Cdc42 activity plays a causal role in defective hematopoiesis-supportive function of the FA MSCs. The progenies of wild-type hematopoietic stem and progenitor cells cocultured on FA MSCs exhibit compromised self-renewal capacity both in vitro and in vivo. Genetic correction of FA deficiency restores Cdc42 activity and improves the hematopoiesis-supportive capacity of FA MSC. Finally, ectopic expression of a constitutively active Cdc42 mutant, Cdc42F28L, or pretreatment with Wnt5a, increases the active Cdc42 level and rescues the hematopoietic supportive defects of FA MSCs. Taken together, our results identify a novel link between Cdc42 activity and the hematopoiesis-supportive function of MSCs and suggest that a niche-specific increase of Cdc42 activity may be beneficial for FA therapy. Stem Cells 2018;36:785-795.


Mucosal assessment for dysplasia and cancer in the ileal pouch mucosa in patients operated on for ulcerative colitis--a 30-year follow-up study.
Sporadic reports of epithelial dysplasia and the occasional development of adenocarcinoma in the ileal pouch mucosa have recently appeared in the literature, pointing toward yet another long-term complication of the continent ileostomy and the pelvic pouch. The incidence of dysplasia and the risk for developing cancer has not been critically evaluated, however, and the reports are contradictory, with most having short observation times. The purpose of this study was to report long-term mucosal adaptation patterns and the incidence of dysplasia in Kock pouches after a mean follow-up of 30 years for patients previously operated on for ulcerative proctocolitis. Two sets of two pathologists each (in Gothenburg, Sweden, and Manchester, United Kingdom) examined sequential, small-intestinal biopsy specimens from 40 patients with Kock pouch to observe long-term epithelial changes, with particular reference to the presence of dysplasia. There was full agreement between the two groups regarding the absence of high-grade dysplasia and invasive carcinoma (Categories 4 and 5 of the Vienna classification). There was, however, significant disagreement in reporting the frequency of low-grade and indefinite categories of dysplasia (Categories 2 and 3, of the Vienna classification). No attempt was made to report the differences within each set of pathologists. Because no case of high-grade dysplasia or invasive carcinoma was found in this study after a mean follow-up of 30 years, we conclude that it is very unlikely for invasive carcinoma to be a complication in ileal pouch mucosa.


Effect of hidden geometry and higher-order interactions on the synchronization and hysteresis behavior of phase oscillators on 5-clique simplicial assemblies.
The hidden geometry of simplicial complexes can influence the collective dynamics of nodes in different ways depending on the simplex-based interactions of various orders and competition between local and global structural features. We study a system of phase oscillators attached to nodes of four-dimensional simplicial complexes and interacting via positive/negative edges-based pairwise K_{1} and triangle-based triple K_{2}≥0 couplings. Three prototypal simplicial complexes are grown by aggregation of 5-cliques, controlled by the chemical affinity parameter ν, resulting in sparse, mixed, and compact architecture, all of which have 1-hyperbolic graphs but different spectral dimensions. By changing the interaction strength K_{1}∈[-4,2] along the forward and backward sweeps, we numerically determine individual phases of each oscillator and a global order parameter to measure the level of synchronization. Our results reveal how different architectures of simplicial complexes, in conjunction with the interactions and internal-frequency distributions, impact the shape of the hysteresis loop and lead to patterns of locally synchronized groups that hinder global network synchronization. Remarkably, these groups are differently affected by the size of the shared faces between neighboring 5-cliques and the presence of higher-order interactions. At K_{1}<0, partial synchronization is much higher in the compact community than in the assemblies of cliques sharing single nodes, at least occasionally. These structures also partially desynchronize at a lower triangle-based coupling K_{2} than the compact assembly. Broadening of the internal frequency distribution gradually reduces the synchronization level in the mixed and sparse communities, even at positive pairwise couplings. The order-parameter fluctuations in these partially synchronized states are quasicyclical with higher harmonics, described by multifractal analysis and broad singularity spectra.


Anterior Chest Wall Non-traumatic Arthropathies: A Crucial but often Overlooked Site.
The purpose of this study was to describe the distribution of Anterior Chest Wall (ACW) arthropathies in a tertiary care center and identify clinical, biological and imaging findings to differentiate osteoarthritis (OA) from non-osteoarthritis (N-OA) etiologies. Search from medical records from January 2009 to April 2022, including patients with manubriosternal and/or sternoclavicular and/or sternocostal joint changes confirmed by ultrasonography, computed tomography or magnetic resonance imaging. The final study group was divided into OA and N-OA subgroups. A total of 108 patients (34 males and 74 females, mean age: 47.3±13 years) were included. Twenty patients had findings of OA, while 88 were diagnosed with N-OA pathologies. SpA was the most common etiology in the N-OA group (n=75). The other N-OA etiologies were less common: rheumatoid arthritis (n=4), Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome (n=3), infectious arthritis (n=3) and microcrystalline arthropathies (n=3). Regarding the distinctive features, ACW pain was the inaugural manifestation in 50% of patients in OA group and 18.2% of patients in N-OA group (p=0.003); high inflammatory biomarkers were more common in N-OA group (p=0.033). Imaging findings significantly associated with OA included subchondral bone cysts (p<0.001) and intra-articular vacuum phenomenon (p<0.001), while the presence of erosions was significantly associated with N-OA arthropathies (p=0.019). OA was independently predicted by the presence of subchondral bone cysts (p=0.026). ACW pain is a common but often underestimated complaint. Knowledge of the different non-traumatic pathologies and differentiation between OA and N-OA etiologies is fundamental for appropriate therapeutic management.


Occupational Therapy for the Long Haul of Post-COVID Syndrome: A Case Report.
Prolonged symptoms from the novel coronavirus disease 2019 (COVID-19), otherwise known as long COVID, postacute sequelae of COVID-19 (PASC), or post-COVID syndrome, are affecting an increasingly high number of patients after severe, moderate, and mild acute COVID-19 infections. Using evidence-based practice strategies, this case report describes occupational therapy evaluation and treatment approaches, plan of care, and associated outcomes for one client experiencing long COVID symptoms in the outpatient setting.


Impact of anesthesia on cardiac function during echocardiography in mice.
Anesthetics provide sedation and immobility facilitating echocardiography in mice, but influence cardiac function. We studied the effects of intraperitoneal and inhaled anesthetic agents on echocardiographic measurements. Mice were anesthetized with intraperitoneal tribromoethanol (TBE), ketamine-midazolam (K/M), ketamine-xylazine (K/X), or inhaled isoflurane (Isf), and echocardiographic parameters were assessed at 5, 10, 15, and 20 min. In C57BL/6N mice, Isf produced high initial heart rates (HR) that decreased to levels comparable to TBE at 15-20 min (approximately 450 beats/min) and the most stable percent fractional shortening (%FS) and end-diastolic dimension (EDD). With TBE, %FS initially was low, but increased comparable to Isf (approximately 45%) at 15 min. K/M produced similar time trends but lower absolute values compared with TBE for all parameters. K/X produced cardiac depression evidenced by low HR and %FS, and increased EDD. Isf was the most reproducible in repeat studies at 12 days. In C57BL/6J compared with C57BL/6N mice, K/M produced higher HR, and %FS and TBE produced smaller EDD. In conclusion, anesthetic agent, timing of echocardiographic measurements, and genetic background are all critical variables during echocardiography in mice.


New ichneumonids (Hymenoptera, Ichneumonidae) from the Eocene Tadushi Formation, Russian Far East.
Ichneumonidae constitute one of the largest families of organisms, but their fossil record is severely understudied, which precludes inferences about their early evolutionary history. We here describe a new genus and two new species of ichneumonids from the Early Eocene Tadushi Formation (Russian Far East). The new taxa are Crusopimpla tadushensis gen. et sp. nov. and Dolichomitus? saxeus sp. nov. Pimpla rediviva (Brues) is redescribed and placed in the genus Crusopimpla. This new genus is unique within Pimplinae in having a completely developed propodeal carination and probably represents one of its most basal lineages. Using a phylogenetic hypothesis of the subfamily, we discuss potential pathways of morphological evolution in the group, which will provide a basis for future placement of pimpline fossil taxa.


Rifampicin-resistant tuberculosis patients in Myanmar in 2016: how many are lost on the path to treatment?
Regional tuberculosis (TB) centres of the Yangon and Mandalay Regions of Myanmar, which account for 65% of all notified rifampicin-resistant tuberculosis (RR-TB) cases countrywide. To determine 1) initial loss to follow-up (LTFU), 2) treatment delay, and 3) factors associated with initial LTFU and treatment delay among RR-TB patients residing in the Yangon and Mandalay regions diagnosed using Xpert® during January-August 2016. This was a retrospective cohort study. Each diagnosed patient was tracked in the drug-resistant TB treatment registers of the Yangon and Mandalay regional treatment centres for January-December 2016 using patient name, age, sex, township and date of diagnosis. If the diagnosed patient was not found in the treatment register by 31 December 2016, he/she was considered 'initial LTFU'. Of the 1037 RR-TB patients diagnosed, 310 (30%) experienced initial LTFU, which was significantly higher among patients aged 55 years and among those diagnosed in the Mandalay Region. A treatment delay of >1 month was observed in 440 (70%) patients (median delay 41 days). Delay was uniformly high across patient subgroups, and was not associated with any factor. Initial LTFU and treatment delays among RR-TB patients were high. Future studies using qualitative research methods are needed to ascertain the reasons for this observation.


Synthesis of the KLMN Fragment of Gymnocin-A from the FGH Fragment.
An improved route for the synthesis of the KLMN fragment of gymnocin-A was developed through the oxiranyl anion coupling of the FGH fragment with a chiral C3 epoxy sulfone, followed by 6-endo cyclization. This straightforward approach reduced the number of synthetic steps by 14 compared with a previous route using alternative building blocks.


Massive lingual swelling following cleft palate repair.
We report two cases of massive tongue edema in routine palatoplasty. All patients had uneventful recovery. We postulated that the macroglossia was secondary to ischemia and venous congestion after prolonged use of Killner Dott mouth gag with slotted tongue blade exaggerated by hyperextension of neck and Trendelenberg position.


Mitral valve replacement: impact of coronary artery disease and determinants of prognosis after revascularization.
From 1969 to 1982, 419 patients underwent single mitral valve replacement; of these, 48% had associated coronary artery disease (9% single vessel, 8% double vessel, 28% triple vessel, 3% left main). In 216 patients with no associated coronary disease, in 179 patients with coronary disease that was revascularized, and in 24 patients with coronary disease that was not revascularized, the 30 day mortalities were 4.2%, 13.9%, and 29.2% (p less than .05) after valve replacement. Actuarial survivals at 8 years were 68%, 44%, and 15%, respectively (p less than .01), with 1 to 165 months of follow-up (mean 52). After matching the three cohorts of patients in age, sex, left ventricular ejection fraction, and valve lesion, the presence of associated coronary artery disease decreased long-term survival and revascularization improved survival (p less than .05 for both). Incidental coronary disease in patients with rheumatic mitral valve disease had a significant negative influence on survival if left unbypassed (p less than .05); after revascularization and valve replacement, the 30 day mortality was 7.3% and the 8 year survival was 52%. Coronary disease etiologically related to ischemic mitral regurgitation identified a high-risk group of patients, with a 30 day mortality of 19.6% and an 8 year survival of 37% after the combined procedure. A multivariate logistic regression model was used to determine which preoperative and intraoperative variables predicted early and late outcome after combined mitral valve replacement and coronary revascularization. Predictors of early death were advanced age (greater than 60 years), New York Heart Association functional class (IV), an ischemic etiology of the mitral valve disease, and a depressed left ventricular ejection fraction (less than 55%). Predictors of late death were triple-vessel or left main coronary disease, increased left ventricular end-diastolic volume (greater than 120 ml/m2), and depressed left ventricular ejection fraction (less than 55%). These findings highlight the important etiologic and prognostic role of coronary artery disease in patients requiring mitral valve replacement.


[Histologic and autoradiographic studies on the significance and terminology of von Brunn's nests in biopsies of the bladder mucosa].
Von Brunn's nests have been investigated systematically by means of histology and autoradiography in 201 biopsies of tumour-free and tumorous urinary bladders. They show the same proliferation behaviour like the superimposed urothelium under normal conditions and with inflammatory, metaplastic and dysplastic changes. Their sheltered location permits definite diagnoses even with detached superficial urothelium. In case of cystic transformation, a distinction between pseudoglandular, pseudopapillary and cribriform types is possible. They have to be distinguished from genuine glandular metaplasias in von Brunn's nests. Normal and metaplastic von Brunn's nests do not represent precancerous stages. They are supposed to be a protected proliferation reserve.


P/Q-type and T-type voltage-gated calcium channels are involved in the contraction of mammary and brain blood vessels from hypertensive patients.
Calcium channel blockers are widely used in cardiovascular diseases. Besides L-type channels, T- and P/Q-type calcium channels are involved in the contraction of human renal blood vessels. It was hypothesized that T- and P/Q-type channels are involved in the contraction of human brain and mammary blood vessels. Internal mammary arteries from bypass surgery patients and cerebral arterioles from patients with brain tumours with and without hypertension were tested in a myograph and perfusion set-up. PCR and immunohistochemistry were performed on isolated blood vessels. The P/Q-type antagonist ω-agatoxin IVA (10-8 mol L-1 ) and the T-type calcium blocker mibefradil (10-7 mol L-1 ) inhibited KCl depolarization-induced contraction in mammary arteries from hypertensive patients with no effect on blood vessels from normotensive patients. ω-Agatoxin IVA decreased contraction in cerebral arterioles from hypertensive patients. L-type blocker nifedipine abolished the contraction in mammary arteries. PCR analysis showed expression of P/Q-type (Cav 2.1), T-type (Cav 3.1 and Cav 3.2) and L-type (Cav 1.2) calcium channels in mammary and cerebral arteries. Immunohistochemical labelling of mammary and cerebral arteries revealed the presence of Cav 2.1 in endothelial and smooth muscle cells. Cav 3.1 was also detected in mammary arteries. P/Q- and T-type Cav are present in human internal mammary arteries and in cerebral penetrating arterioles. P/Q- and T-type calcium channels are involved in the contraction of mammary arteries from hypertensive patients but not from normotensive patients. Furthermore, in cerebral arterioles P/Q-type channels importance was restricted to hypertensive patients might lead to that T- and P/Q-type channels could be a new target in hypertensive patients.


Characterization of retinal and blood mitochondrial DNA from age-related macular degeneration patients.
To determine mitochondrial (mt)DNA variants in AMD and age-matched normal retinas. Total DNA was isolated from retinas (AMD, n = 13; age-matched normal, n = 13), choroid (AMD, n = 3), and blood (AMD, n = 138; normal, n = 133). Long-extension-polymerase chain reaction amplified the full-length ( approximately 16.2 kb) mtDNA genome. Retinal mtDNA was sequenced for nucleotide variants and length heteroplasmy. Pyrosequencing was performed on heteroplasmic mtDNA. PCR amplification and enzyme digestions were used to analyze for nucleotide changes. Retinal mtDNA had a greater number of rearrangements and deletions than did blood mtDNA in normal samples (9.3 +/- 1.78 vs. 3 +/- 1.18, P = 0.019), and AMD samples (14.33 +/- 1.96 vs. 5.2 +/- 0.80, P = 0.0031. Five (55%) of 9 AMD patients had unreported SNPs, and 2 (16.6%) of 12 of the normal group did. The mtDNA coding region had 20 SNPs that produced amino acid changes. The noncoding MT-Dloop region had nucleotide heteroplasmy and length heteroplasmy. There were more SNPs per person in the AMD population than in the older (P = 0.003) and younger (P = 0.05) normal subjects. The C12557T (T-I) in the MT-ND5 gene was present in two AMD subjects (2/138) but was absent in the normal (0/133). Common mutations for Leber's hereditary optic neuropathy (LHON: G11778A; T14484C; and G3460A) were not present in AMD samples. AMD subjects have high levels of large mtDNA deletions/rearrangements in the retinas, unreported and amino acid-changing SNPs in the coding genome, and a greater number of SNPs per person in the noncoding MT-Dloop region. These mtDNA variants could diminish energy production efficiency, alter the mtDNA copy numbers and/or impact transcription in AMD retinas.


Secondary alcohol dehydrogenase catalyzes the reduction of exogenous acetone to 2-propanol in Trichomonas vaginalis.
Secondary alcohols such as 2-propanol are readily produced by various anaerobic bacteria that possess secondary alcohol dehydrogenase (S-ADH), although production of 2-propanol is rare in eukaryotes. Specific bacterial-type S-ADH has been identified in a few unicellular eukaryotes, but its function is not known and the production of secondary alcohols has not been studied. We purified and characterized S-ADH from the human pathogen Trichomonas vaginalis. The kinetic properties and thermostability of T. vaginalis S-ADH were comparable with bacterial orthologues. The substantial activity of S-ADH in the parasite's cytosol was surprising, because only low amounts of ethanol and trace amounts of secondary alcohols were detected as metabolic end products. However, S-ADH provided the parasite with a high capacity to scavenge and reduce external acetone to 2-propanol. To maintain redox balance, the demand for reducing power to metabolize external acetone was compensated for by decreased cytosolic reduction of pyruvate to lactate and by hydrogenosomal metabolism of pyruvate. We speculate that hydrogen might be utilized to maintain cytosolic reducing power. The high activity of Tv-S-ADH together with the ability of T. vaginalis to modulate the metabolic fluxes indicate efficacious metabolic responsiveness that could be advantageous for rapid adaptation of the parasite to changes in the host environment.


Allicin inclusions with α-cyclodextrin effectively masking its odor: Preparation, characterization, and olfactory and gustatory evaluation.
Allicin, a chemical found in functional foods, has a variety of beneficial bioactivities but the unpleasent odor and unstability hinder its applications. Isolating products from cyclodextrin (CD) complexation, using β-CD and its derivatives, is usually a time and energy-consuming process. Herein, a high-efficiency and eco-friendly preparation method of an inclusion (allicin@α-CD) formed by allicin and α-CD was designed, which turned liquid allicin into crystal particles with high-speed stirring (10,000 r/min) at 25°C for 10 min in water. In vivo and in vitro masking evaluations showed that the inclusion particles could decrease the unpleasant odor of allicin. Molecular docking and experimental characterization results illustrated that the main reason of odor masking was due to the disulfide and thiocarbonyl groups of allicin being partially encapsulated by the cavity of α-CD. Compared with the physical mixture, the stability of allicin in allicin@α-CD at 60°C for 10 days was 33-fold improved. Overall, this efficient strategy of inclusion provided a promising approach for the industrialization of allicin-related formulations. PRACTICAL APPLICATION: In this study, an environmentally friendly method of α-CD inclusion without the use of organic reagents was designed to solidify and stabilize allicin, which effectively masked the unpleasant odor and taste of allicin. It has contributed greatly to improving the compliance of consumers and provided a new and effective approach to broaden the application of allicin.


Effect of felodipine on regional blood supply and collateral vascular resistance in patients with peripheral arterial occlusive disease.
This double-blinded, randomized, placebo-controlled study was designed to investigate the acute effect of felodipine on regional blood supply and collateral vascular resistance in patients with peripheral arterial occlusive disease (PAOD). Thirty men with PAOD were treated with a single dose of 5 mg felodipine or placebo. Systolic blood pressure (SBP), Doppler ankle pressure (DAP), calf blood flow (CBF) by venous occlusion plethysmography and calf transcutaneous oxygen tension (tcpO2) were measured during a cycle ergometry. Felodipine reduced SBP significantly (from 149 to 136 mmHg, p < 0.05), while placebo did not. DAP increased slightly but not significantly in both groups. The pressure gradient between SBP and DAP fell significantly in the felodipine group (60 vs 39 mmHg, p < 0.01) but not in the placebo group (59 vs 56 mmHg). There was a trend for lower velocity in tcpO2 decrease during the stress test and higher velocity of tcpO2 increase during recovery from exercise in the felodipine group although the differences between both groups were not significant. In the felodipine group, CBF increased by 35.6% (p < 0.05) whereas it did not change in the placebo group. In conclusion, while lowering SBP, felodipine increased slightly, or at least maintained, the blood supply to the calves in PAOD patients, which probably results from reducing collateral vascular resistance.


The diagnostic accuracy of tests for latent tuberculosis infection in hemodialysis patients: a systematic review and meta-analysis.
Reactivation of latent Mycobacterium tuberculosis infection is an important health concern for patients on hemodialysis because of their immunosuppressed state and in kidney transplant patients receiving immunosuppressive therapy to prevent organ rejection. There are several tests available to determine the presence of latent tuberculosis infection: the tuberculin skin test (TST), QuantiFERON-TB Gold (QFT-G), and T-SPOT.TB. The objective of this study is to evaluate the diagnostic accuracy of these tests in determining latent tuberculosis infection in the hemodialysis population. The study design was a systematic review. We selected studies with adequate information to ascertain test sensitivity or specificity of the TST, QFT-G, and TSPOT.TB with regards to determining latent tuberculosis infection in the hemodialysis population. One hundred two articles were selected for full review, and 17 were included in the meta-analysis. The TST had a pooled sensitivity of 31% (26%-36%, 95% confidence interval) and specificity of 63% (60%-65%) across eight studies. The QFT-G test had a pooled sensitivity of 53% (46%-59%) and specificity of 69% (65%-72%) across nine studies. The T-SPOT.TB test had a pooled sensitivity of 50% (42%-59%) and specificity of 67% (61%-73%) across three studies. The QFT-G and the T-SPOT.TB tests were more sensitive than the TST for diagnosis of latent tuberculosis infection in patients on hemodialysis while offering a comparable level of specificity. This systematic review calls into question the practice of using the TST to screen in this population, especially in patients considered for kidney transplantation.


Physical function of elderly patients with multimorbidity upon acute hospital admission versus 3 weeks post-discharge.
To evaluate the change in activities of daily living, grip strength and functional mobility in very old patients >75 years old with multimorbidity upon admission to hospital versus 3 weeks after discharge. A second aim was to explore which baseline variables could predict personal activities of daily living 3 weeks after discharge. This prospective cohort study included 115 home-dwelling older adults (mean 86 years, standard deviation 5.9). Participants were measured with the Timed Up and Go, grip strength and Barthel Index in hospital (T1) and 3 weeks after discharge (T2). After 3 weeks, the participants had significantly improved their activities of daily living, mobility and muscle strength, but were still physically reduced compared to reference values for age-matched elderly home dwellers and were at high risk of falls and further loss of independence. In the multivariate regression analysis, baseline cognitive function and mobility were independently associated with Barthel Index at T2 and explained 47% of the variance three weeks after discharge. Our findings highlight the importance of applying performance-based assessments for elderly in hospital. The result indicates that frail old adults acutely admitted to hospital are in need of rehabilitation 3 weeks after hospitalization. Implications for Rehabilitation Older people with multimorbidity improve their physical function 3 weeks after hospitalization. Nevertheless, they still are physically reduced with respect to reference values for age-matched elderly home dwellers and far below the cutoff score for their risk of falls, continued health decline and loosing their independence. The results imply that older people with multimorbidity are in need of early rehabilitation program during hospitalization and after hospitalization. The use of performance-based measurements enables us to identify older adults at highest risk of decline in health and function and is a key of identifying frail older peoples need for rehabilitation. The Time up and Go test, Grip Strength test and the Barthel Index are considered to complement each other and regarded as useful assessments for frail older people in hospital with acute illness.


The effects of increasing stimulus complexity in event-related potentials and reaction time testing: clinical applications in evaluating patients with traumatic brain injury.
This study compared the effectiveness of P300 event related potentials (ERPs) and reaction time (RT) in discriminating patients with traumatic brain injury (TBI) from healthy control subjects. In particular, we examined how the use of more complex, ecologically relevant stimuli may affect the clinical utility of these tasks. We also evaluated how length of posttraumatic amnesia (PTA) and loss of consciousness (LOC) related to P300 and RT measures in our patient sample. There were 22 subjects (11 patients with TBI and 11 age-matched healthy control subjects). Four stimulus detection procedures were used: two using simple, conventional stimuli (auditory tone discrimination, AT; visual color discrimination, VC), and two using complex, ecologically relevant stimuli in the auditory and visual modalities (auditory word category discrimination, AWC; visual facial affect discrimination, VFA). Our results showed that RT measures were more effective in identifying TBI patients when complex stimuli were used (AWC and VFA). On the other hand, ERP measures were more effective in identifying TBI patients when simple stimuli were used (AT and VC). We also found a remarkably high correlation between duration of PTA and P300 amplitude.


Liquid sampling-atmospheric pressure glow discharge as a secondary excitation source for laser ablation-generated aerosols: parametric dependence and robustness to particle loading.
Liquid sampling-atmospheric pressure glow discharge (LS-APGD) microplasma is being developed as a secondary vaporization-excitation source for the optical emission analysis of laser ablation (LA)-generated particle populations. The practicalities of this coupling are evaluated by determining the influence of source parameters on the emission response and the plasma's robustness upon LA introduction of easily ionized elements (EIEs). The influence of discharge current (45-70 mA), LA carrier gas flow rate (0.1-0.8 L min(-1)), and electrode separation distance (0.5-3.5 mm) was studied by measuring Cu emission lines after ablation of a brass sample. Best emission responses were observed for high-discharge currents, low He carrier gas flow rates, and relatively small (<1.5 mm) electrode gaps. Plasma robustness and spectroscopic matrix effects were studied by monitoring Mg(II) : Mg(I) intensity ratios and N2-derived plasma rotational temperatures after the ablation of Sr- and Ca-containing pellets. Plasma robustness investigations showed that the plasma is not appreciably affected by the particle loadings, with the microplasma being slightly more ionizing in the case of Ca introduction. In neither case did the concentration of the concomitant element change the robustness values, implying a high level of robustness. Introduction of the LA particles results in slight increases in the rotational temperatures (∼10% relative), with Ca-containing particles having a greater effect than Sr-containing particles. The observed variation of 9% in the plasma rotational temperature is in the same order of magnitude as the short-term reproducibility determined by the proposed LA-LS-APGD system. The determined rotational temperatures ranged from 1047 to 1212 K upon introducing various amounts of Ca and Sr. The relative immunity to LA particle-induced matrix effects is attributed to the relatively long residence times and high power densities (>10 W mm(-3)) of the LS-APGD microplasma.


Radiochemotherapy upregulates expression of checkpoint receptors on circulating T cells.
This study assesses changes of circulating leukocyte subpopulations and the expression of checkpoint receptors in T cells in patients undergoing radiochemotherapy. Fifty-seven patients with either esophageal cancer or cervical cancer who received radiochemotherapy were recruited into this study. Serial blood collection was carried out before and during treatments. Leukocyte subpopulations and the level of PD-1 and CTLA-4 in T cells were determined by flow cytometry. The plasma concentrations of 34 human cytokines, chemokines, and growth factors were quantified. Significant decreases of lymphocyte count and percentage of T cells and B cells were observed during radiochemotherapy. Percentages of PD-1hi and CTLA-4hi populations in T cells increased after treatments. Proportion of activated T cells showed no significant difference. No significant changes in the plasma concentrations of the 34 humoral mediators except mild decreases of six cytokines. Elevated expression of PD-1 and CTLA-4 in T cells in patients receiving radiochemotherapy, which suggests that exhaustion-like T-cell dysfunction develops during cancer cytotoxic treatments.


Singular extremals for the time-optimal control of dissipative spin 1/2 particles.
We consider the time-optimal control by magnetic fields of a spin 1/2 particle in a dissipative environment. This system is used as an illustrative example to show the role of singular extremals in the control of quantum systems. We analyze a simple case where the control law is explicitly determined. We experimentally implement the optimal control using techniques of nuclear magnetic resonance. To our knowledge, this is the first experimental demonstration of singular extremals in quantum systems with bounded control amplitudes.


Preparation of novel three-dimensional NiO/ultrathin derived graphene hybrid for supercapacitor applications.
A new type of three-dimensional (3D) NiO/ultrathin derived graphene (UDG) hybrid on commercial Ni foam (NF) for a binder-free pseudocapacitor electrode is presented. NiO nanoflakes are in situ grown by a chemical bath deposition (CBD) technique on the free-standing 3D UDG/NF scaffold, which is first prepared by a simple nanocasting process consisting of hydrothermal reaction and subsequent thermal transformation. The 3D UDG/NF scaffold with interconnected network affords a high conductivity due to the high graphitization degree and efficiently facilitates the electron transport to NiO. Moreover, the 3D NiO/UDG/NF hybrid allows for a thinner 3D active material layer under the same loading density, which could shorten the diffusion paths of ions. The NiO/UDG/NF hybrid is directly used as a binder-free supercapacitor electrode, which exhibited significantly improved supercapacitor performance compared to the bare CBD prepared NiO/NF electrode.


Long Term Prognostic Implications of Expression of Glucose Transporter-1 and Hexokinase II in Patients with Stage I Uterine Leiomyosarcoma.
Many malignant epithelial tumors show increased expression of glucose transporter-1 (GLUT-1) and hexokinase II (HK-II), both of which are involved in glucose metabolism. GLUT-1 levels are often correlated with prognosis in these tumors. The current retrospective study was conducted to evaluate the importance of GLUT-1 and HK-II expression in leiomyosarcoma (LMS), a malignant uterine non-epithelial tumor with a poor prognosis. The subjects were 23 patients with stage I LMS. Expression of GLUT-1 and HK-II was evaluated immunohistochemically in samples removed surgically, and the MIB-1 index was evaluated as a measure of cell proliferation. The association of these results with prognosis was examined. Twenty samples of leiomyoma (LOM), a benign non-epithelial tumor, were used as controls. Immunohistochemical expression was defined as negative staining (-), weak to sporadic staining (1+), and strong staining (2+) per microscopic field, respectively. Malignancy was evaluated in 2000 cells and the MIB-1 index was calculated. Overall survival for LMS was estimated using the Kaplan-Meier method. Of the LMS cases, 12 were GLUT-1-positive (52.2%; 2+: 2, 1+: 10) and 15 were HK-II-positive (65.2%; 2+: 1, 1+: 14). GLUT-1 expression in LMS was significantly correlated with the MIB1 index. The 10-year survival rates were 90.9% and 58.3% in GLUT-1-negative and GLUT-1-positive cases, respectively, and 75.0% and 73.3% in HK-II-positive and HK-II-negative cases, respectively. GLUT-1 expression was significantly correlated with prognosis. Cases of stage I LMS showed a significant correlation between the expression level of GLUT-1 and the MIB-1 index, an indicator of malignancy. GLUT-1-negative cases had a better prognosis than GLUT-1-positive cases, suggesting that GLUT-1 expression is an effective prognostic marker.


STRATEGIES IN ADDRESSING STATE SCREEN TIME POLICIES IN EARLY CARE AND EDUCATION CENTERS IN LOUISIANA.
Multiple state and local governments have legislated screen time policy regulations in early care and education (ECE) centers in the United States, though little is known about how and whether these are enacted within these settings. This study examined the implementation, communication, monitoring, enforcement, and evaluation strategies of recently enacted state-level early childhood education (ECE) center screen time regulations in a southern U.S. state. ECE directors (n=12) participated in semi-structured interviews after the regulations were enacted, and interview transcripts were evaluated using thematic analysis. Most directors reported making environmental changes (e.g., removing screens from the classroom) and limiting children's and staff members' access to devices (e.g., restricting classroom time spent on screens), including regulating staff members' own screen time (i.e., phone usage). ECE center directors reported daily monitoring for adherence to regulations and used a variety of enforcement strategies, and most reported no adverse effects from implementing the policy. A few directors reported receiving resources from agencies or organizations to assist in implementing, monitoring, or enforcing screen time regulations. In this sample, environmental and individual changes helped ECE centers adhere to the regulations, along with frequent monitoring. Development of technical assistance resources to support environmental and logistical changes, along with continued evaluation of the regulations, are warranted to minimize or eliminate screen time at ECE centers.


New technologies accelerate the exploration of non-coding RNAs in horticultural plants.
Non-coding RNAs (ncRNAs), that is, RNAs not translated into proteins, are crucial regulators of a variety of biological processes in plants. While protein-encoding genes have been relatively well-annotated in sequenced genomes, accounting for a small portion of the genome space in plants, the universe of plant ncRNAs is rapidly expanding. Recent advances in experimental and computational technologies have generated a great momentum for discovery and functional characterization of ncRNAs. Here we summarize the classification and known biological functions of plant ncRNAs, review the application of next-generation sequencing (NGS) technology and ribosome profiling technology to ncRNA discovery in horticultural plants and discuss the application of new technologies, especially the new genome-editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems, to functional characterization of plant ncRNAs.


Mechanisms underlying reduced expulsion of a murine nematode infection during protein deficiency.
Balb/c mice infected with the gastrointestinal nematode Heligmosomoides bakeri were fed protein sufficient (PS, 24%) or deficient (PD, 3%) diets to investigate whether diet, infection or dose of larval challenge (0, 100 or 200 larvae) influenced gut pathophysiology and inflammation. Among the PS mice, worms were more posteriorad in the intestine of mice infected with 200 compared with 100 larvae, suggesting active expulsion in the more heavily infected mice. This was consistent with the positive correlation between worm numbers and fluid leakage in PS mice; similar patterns were not detected in the PD mice. Infection also induced villus atrophy, which was more pronounced in PS than in PD mice. Our cytokine screening array indicated that infection in PD mice elevated a wide range of pro-inflammatory cytokines and chemokines. Whereas serum leptin concentrations were higher in PD mice, monocyte chemotactic protein-5 (MCP-5) in serum increased with increasing larval dose and concentrations were lower in PD than PS mice. We suggest that elevated MCP-5 together with villus atrophy may contribute to the apparent dose-dependent expulsion of H. bakeri from PS mice but that delayed expulsion in PD mice appeared related to a predominant Th1 cytokine profile that may be driven by leptin.


Visual attention in infant monkeys: effects of dietary fatty acids and age.
Effects of dietary essential fatty acids on visual attention were explored longitudinally in infant rhesus monkeys with a visual paired-comparison paradigm. Sets of primate faces and of patterns were presented at Weeks 2, 5, 9, and 13 to 9 infants deficient in omega-3 fatty acids and 8 fed a standard nursery diet. Familiarization to 1 member of each pair preceded simultaneous presentation of both stimuli. Infants fed the deficient diet showed longer individual looks in both immediate and 24-hr tests. Duration of looks decreased with age to familiar but not to novel stimuli. The proportion of time looking at the novel stimulus (% novel) increased with age but was not affected by diet. Look duration and % novel were differentially affected and may reflect different underlying processes.


Selection of key sequence-based features for prediction of essential genes in 31 diverse bacterial species.
Genes that are indispensable for survival are essential genes. Many features have been proposed for computational prediction of essential genes. In this paper, the least absolute shrinkage and selection operator method was used to screen key sequence-based features related to gene essentiality. To assess the effects, the selected features were used to predict the essential genes from 31 bacterial species based on a support vector machine classifier. For all 31 bacterial objects (21 Gram-negative objects and ten Gram-positive objects), the features in the three datasets were reduced from 57, 59, and 58, to 40, 37, and 38, respectively, without loss of prediction accuracy. Results showed that some features were redundant for gene essentiality, so could be eliminated from future analyses. The selected features contained more complex (or key) biological information for gene essentiality, and could be of use in related research projects, such as gene prediction, synthetic biology, and drug design.


Influence of Deposition Time on Titanium Nitride (TiN) Thin Film Coating Synthesis Using Chemical Vapour Deposition.
Titanium nitride (TiN) thin film coatings were grown over silicon (p-type) substrate using the atmospheric pressure chemical vapour deposition (APCVD) technique. The synthesis process was carried out to evaluate the effect of deposition time on the physical and mechanical characteristics of TiN coating. Thin films grown over Si substrate were further characterised to evaluate the morphological properties, surface roughness and mechanical properties using a scanning electrode microscope (SEM), atomic force microscopy (AFM) and nanoindentation, respectively. EDS equipped with SEM showed the presence of Ti and N elements in considerable amounts. TiN morphology obtained from the SEM test showed small-sized particles on the surface along with cracks and pores. AFM results revealed that by increasing the deposition time, the surface roughness of the coating also increased. The nanomechanical properties such as nanohardness (H) and Young's modulus (E), etc., evaluated using the nanoindentation technique showed that higher deposition time led to an increase in H and E. Overall, it was observed that deposition time plays a vital role in the TiN coating deposition using the CVD technique.


Time course of platelet aggregation during thrombolytic treatment of massive pulmonary embolism.
We studied changes in platelet aggregation and fibrinogen levels during thrombolysis with massive or submassive pulmonary embolism. Fifteen patients were randomized into ultrahigh-dose streptokinase (UH-SK n = 8) or alteplase (tPA n = 7) groups. Arterial blood samples were taken before and after thrombolysis every 4 h between 4 and 36 h, and once daily between 2 and 30 days. In-vitro platelet aggregation was examined as spontaneous (0.9% NaCl) and induced aggregation with adrenaline 10 micromol/l, collagen 2 microg/ml and ADP 10 micromol/l. D-dimer and fibrinogen were measured every 8 h on first day, and later as above. In the UH-SK group, adrenaline-induced platelet aggregation decreased at 4 and 8 h compared with baseline (P < 0.03). Adrenaline-induced platelet aggregation was significantly lower in the UH-SK group than in the tPA group at 36 h and on day 3 (P < 0.03). Platelet aggregation induced by ADP was lower at 4 h than at baseline in the UH-SK group (P < 0.05). Collagen-induced platelet aggregation was lower at 4 and 8 h than at baseline (P < 0.05) in the UH-SK group. Compared with baseline, fibrinogen levels decreased in both groups after thrombolysis. D-dimer levels were elevated in both groups at 8 h (tPA group, P < 0.0004; UH-SK group, P < 0.05). Spontaneous platelet aggregation, major bleeding or re-embolism was not documented. Platelet aggregation decreased after thrombolysis with UH-SK for 12 h, in comparison tPA caused an insignificant decrease. Fibrinogen level decreased with UH-SK treatment for 5 days but in case of tPA we could not measure significant changes. According to our findings, tPA is a more suitable drug but streptokinase is also effective because of its cost-benefit ratio.