Imaging Alzheimer pathology in late-life depression with PET and Pittsburgh Compound-B.
There is increasing evidence for an empiric link between late-life depression and Alzheimer disease (AD). The neuropathology of AD, previously only confirmed at autopsy, may now be detectable in vivo using selective imaging ligands for beta-amyloid. Positron emission tomography (PET) with [11C] 6-OH-BTA-1 [Pittsburgh Compound-B (PiB)] has shown high tracer retention in cortical areas in patients with clinical diagnoses of probable AD and low retention in age-matched controls. We also previously reported variable PiB retention in patients with mild cognitive impairment (MCI). In this study, we used PiB-PET to evaluate whether amyloid is present in elders with treated major depression, many of whom have persistent cognitive impairment. We evaluated 9 subjects with remitted major depression [3M: 6F, mean (SD) age=71.8(5.7) y]. Seven of the 9 depressed subjects also met criteria for the diagnosis of MCI. PiB-PET data from healthy elders [n=8; mean (SD) age=71.5(3.0) y] were used for comparison. PET was acquired with arterial sampling and PiB retention was quantified using magnetic resonance imaging-guided cortical regions and graphical analysis of time-activity data; arterial line failure led to exclusion of 1 depressed subject. The data demonstrated variably elevated PiB retention. PiB retention in the 2 depressed subjects with normal cognitive ability was in the range of nondepressed cognitively normal subjects. PiB retention in 3 of the 6 depressed subjects with MCI fell in the range of subjects with AD. PiB retention in the remaining 3 depressed subjects with cooccurring MCI was variable and generally was intermediate to the other subjects. Our findings are consistent with and supportive of the hypothesis that depression may herald the development of AD in some individuals.


Clonal Patch Size and Ramet Position of Leymus chinensis Affected Reproductive Allocation.
Reproductive allocation is critically important for population maintenance and usually varies with not only environmental factors but also biotic ones. As a typical rhizome clonal plant in China's northern grasslands, Leymus chinensis usually dominates the steppe communities and grows in clonal patches. In order to clarify the sexual reproductive allocation of L. chinensis in the process of the growth and expansion, we selected L. chinensis clonal patches of a range of sizes to examine the reproductive allocation and allometric growth of the plants. Moreover, the effects of position of L. chinensis ramets within the patch on their reproductive allocation were also examined. Clonal patch size and position both significantly affected spike biomass, reproductive tiller biomass and SPIKE/TILLER biomass ratio. From the central to the marginal zone, both the spike biomass and reproductive tiller biomass displayed an increasing trend in all the five patch size categories except for reproductive tiller biomass in 15-40m2 category. L. chinensis had significantly larger SPIKE/TILLER biomass ratio in marginal zone than in central zone of clonal patches that are larger than 15 m2 in area. Regression analysis showed that the spike biomass and SPIKE/TILLER biomass ratio were negatively correlated with clonal patch size while patch size showed significantly positive effect on SEED/SPIKE biomass ratio, but the reproductive tiller biomass and SEED/TILLER biomass ratio were not dependent on clonal patch size. The relationships between biomass of spike and reproductive tiller, between mature seed biomass and spike biomass and between mature seed biomass and reproductive tiller biomass were significant allometric for all or some of patch size categories, respectively. The slopes of all these allometric relationships were significantly different from 1. The allometric growth of L. chinensis is patch size-dependent. This finding will be helpful for developing appropriate practices for the management of L. chinensis-dominant grasslands.


Developing a comprehensive model for underwater MIMO OCC system.
Due to its spatial modulation feature and potential applications, optical camera communication (OCC) has gained significant attention in recent years for a range of applications including underwater. Nonetheless, due to the low frame rates of the camera, the OCC data rate is rather low, which is why multiple-input-multiple-output (MIMO) has been adopted to compensate. In MIMO systems, however, the signal from one light emitting diode (LED) may result in interference on the image sensor (i.e., the camera) resulting in inter-pixel interference (IPI). This paper presents a comprehensive model of the underwater OCC (UOCC) and experimentally verifies its performance under IPI by comparing signal to interference and noise ratio (SINR). The effect of distance between LEDs according to LED diameter D on signal to interference ratio (SIR) is presented and results indicate that coastal water has the SIR gain ∼2.5 dB for the link span of 1 to 6 m, and for harbor water channel length from 0.4 to 1.4 m the gain increased from ∼2 to ∼5 dB for d of 2D compared with d of 0.5D.


Fabrication of novel layer-by-layer assembly films composed of poly(lactic acid) and polylysine through cation-dipole interactions.
Novel layer-by-layer (LbL) assembly films composed of poly( L-lysine) (PLL) and poly( D-lactic acid) (PDLA) were prepared by the alternate immersion of a gold substrate into an aqueous PLL solution and an acetonitrile solution of PDLA. The formation of the LbL assembly film was confirmed by quartz crystal microbalance (QCM) analysis, atomic force microscopy observation, and attenuated total reflection Fourier transform infrared spectroscopy measurement. The driving force responsible for the LbL assembly was determined by investigating the formation behavior of the LbL assembly under various conditions. The formation of the LbL assembly was not affected either by the stereochemistry of polylysine and poly(lactic acid) or by the addition of urea, which is known to inhibit hydrogen bonding interaction between polymers, into the aqueous PLL solution. The LbL assembly was also formed by the combination of PDLA and polycations other than polylysine, such as poly(diallyldimethylammonium chloride). On the other hand, the combination of PDLA and any polyanions such as poly(styrene sulfonate sodium salt) produced little corresponding LbL assembly. The increase in positive charge on the amino nitrogen atom of PLL enhanced the LbL assembly. These results suggest that the LbL assembly film composed of PLL and PDLA was fabricated by cation-dipole interactions between the positive charge on the amino nitrogen atom of PLL and the lone pairs of the carbonyl oxygen atom of PDLA.


The Sister Study Cohort: Baseline Methods and Participant Characteristics.
The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m2 (70%). Few (5%) reported any cancer prior to enrollment. The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.


MATERNAL ANCESTRY OF THE RUTILUS ALBURNOIDES COMPLEX (TELEOSTEI, CYPRINIDAE) AS DETERMINED BY ANALYSIS OF CYTOCHROME b SEQUENCES.
Cytochrome b (cyt b) sequences from specimens of the Rutilus alburnoides unisexual complex and five bisexual species were compared to examine hypotheses regarding the origin and maternal ancestry of this complex. Phylogenetic analysis revealed a monophyletic relationship among unisexuals and Leuciscus pyrenaicus, clearly identifying this species as the maternal ancestor. Considerable mtDNA diversity exists among R. alburnoides populations, with many localities exhibiting unique haplotypes. The topology recovered from analysis of cyt b variation among populations suggested that R. alburnoides is polyphyletically derived from their sympatric L. pyrenaicus populations, indicating that unisexual lineages have been generated through multiple hybridization events. Although much less abundant, R. alburnoides is present outside the range of L. pyrenaicus, suggesting that it may have dispersed from the Tejo drainage into the northern basins. In this region, Leuciscus carolitertii is most likely the sexual host for the unisexual complex.


Cell-cycle-related staining patterns of anti-proliferating cell nuclear antigen monoclonal antibodies. Comparison with BrdUrd labeling and Ki-67 staining.
Monoclonal antibodies (MAbs) to nuclear antigens are increasingly used as tools to obtain valuable information concerning the proliferative characteristics of various types of cancer. Prerequisite for the application of these MAbs in surgical pathology is establishment of the level of expression and/or cellular distribution of the antigens in relation to distinct cell-cycle compartments. In this study the topologic distribution of proliferating cell nuclear antigen (PCNA), an auxiliary protein of DNA polymerase delta, as recognized by human autoantiserum (AK) and two recently developed MAbs (19A2 and 19F4), was evaluated. Using cultured human cancer cells as a model system, and providing optimal fixation/permeation procedures are applied, these antibodies display a high affinity for PCNA bound to nuclear replicon clusters, resulting in distinct granular staining patterns. A more diffuse nucleoplasmic PCNA staining was mainly restricted to non-S-phase cells; in methanol-fixed cells, staining intensity of this form relative to the replicon-bound form appeared higher after staining with 19A2 than with 19F4 or AK. Comparing PCNA expression (detected with 19A2) with the expression of the Ki-67 antigen, PCNA-negative cells are also Ki-67 negative. In MCF-7 human breast cancer cells treated with 10(-6) mol/l (molar) tamoxifen, the fraction of nuclei showing replication patterns decreased from 42% to 8% within 8 days, but PCNA and Ki-67 antigens remained detectable in most cells during this interval, indicating a relatively slow decrease of antigen expression in cells that have entered a quiescent state. Treatment of MCF-7 cells with 10(-6) mol/l methotrexate resulted in a rapid accumulation of cells with an early S-phase DNA content; PCNA replication patterns showing a frequency distribution reflecting this DNA content were observed up to 48 hours after treatment. This indicates that the presence of replication patterns as visualized with anti-PCNAs is not a measure of replicative activity per se. It is concluded that, providing nuclear non-S-phase PCNA staining is faint relative to staining of replicon clusters, anti-PCNA antibodies may be excellent markers to detect in situ cells with S-phase DNA contents.


Two-year longitudinal changes in forearm cortical bone geometry in postmenopausal women with mild primary hyperparathyroidism without parathyroidectomy.
Several studies suggest that mild PTH excess does not have any deteriorative effects on bone mineral density (BMD) in several-year-longitudinal studies of patients with mild primary hyperparathyroidism (pHPT) without parathyroidectomy (PTX). However, it remains unknown about the change in bone geometry in pHPT patients without PTX. We examined the longitudinal effects of mild PTH excess on cortical bone geometry in postmenopausal patients with mild pHPT without PTX by using peripheral quantitative computed tomography (pQCT), and we compared them with normal and hypoparathyroidism women. Nine postmenopausal female patients who were diagnosed as pHPT, six postmenopausal female patients with hypoparathyroidism (3 idiopathic and 3 postoperative), and thirty postmenopausal control subjects participated in this study. Radial volumetric (v) BMD and several bone geometry parameters were measured by pQCT at basal line and after 2 years. Cortical vBMD was significantly lower in pHPT group. Moreover, total area and periosteal circumferences were significantly higher in pHPT group. Total and cortical vBMD were significantly decreased after 2 years in control group. However, they were stable in pHPT group after 2-year follow-up. As for bone geometry, cortical thickness and area were also stable in pHPT group during 2-year follow-up, although they were significantly reduced in control group and hypoparathyroidism group. In conclusion, the present longitudinal study revealed that there were no significant changes in radial vBMD and cortical bone geometry in postmenopausal women with mild pHPT, whereas age-related thinning of cortical bone as well as decrease of vBMD were observed in the control and patients with hypoparathyroidism.


Current Diagnostic Criteria for Neurocysticercosis.
Neurocysticercosis (NCC) causes significant neurological morbidity around the world, and is the most common preventable factor for epilepsy in adults. It is endemic in most developing countries, and also diagnosed with some frequency in industrialized countries because of travel and migration. The clinical manifestations of NCC are extremely variable and may include almost any neurological symptom, depending on the number of lesions, location, size and evolutive stage of the infecting parasitic larvae and the immune response of the host. Thus, the diagnosis of NCC relies mostly on neuroimaging and immunological tests. Despite being a disease with a known etiology, the lack of specificity of clinical manifestations and auxiliary examinations makes its diagnosis difficult. In an attempt for developing a standard diagnosis approach, a chart of diagnostic criteria for NCC was initially published in 1996, and revised in 2001 and 2017. This chart of diagnostic criteria systematized the diagnosis of NCC and became widely used worldwide. This manuscript describes the structure of the chart, the principles behind the changes for each revision, as well as the context of its use and potential for improvement.


[Mindfulness-based Stress Reduction (MBSR)].
In the context of an increasing interest in mindfulness-based approaches both in clinical application as well as in the field of research the present paper introduces MBSR (Mindfulness-based Stress Reduction), illustrates the theoretical background of mindfulness practice and reviews the procedures during the cultivation of mindfulness and possible impacting factors. The article also reviews Mindfulness-based Cognitive Therapy (MBCT), which was specifically developed to prevent relapse in patients with depressive disorders. The paper ends with a conclusion for clinical practice.


FDG-PET versus Amyloid-PET Imaging for Diagnosis and Response Evaluation in Alzheimer's Disease: Benefits and Pitfalls.
In June 2021, the US Federal Drug and Food Administration (FDA) granted accelerated approval for the antibody aducanumab and, in January 2023, also for the antibody lecanemab, based on a perceived drug-induced removal of cerebral amyloid-beta as assessed by amyloid-PET and, in the case of lecanemab, also a presumption of limited clinical efficacy. Approval of the antibody donanemab is awaiting further data. However, published trial data indicate few, small and uncertain clinical benefits, below what is considered "clinically meaningful" and similar to the effect of conventional medication. Furthermore, a therapy-related decrease in the amyloid-PET signal may also reflect increased cell damage rather than simply "amyloid removal". This interpretation is more consistent with increased rates of amyloid-related imaging abnormalities and brain volume loss in treated patients, relative to placebo. We also challenge the current diagnostic criteria for AD based on amyloid-PET imaging biomarkers and recommend that future anti-AD therapy trials apply: (1) diagnosis of AD based on the co-occurrence of cognitive decline and decreased cerebral metabolism assessed by FDA-approved FDG-PET, (2) therapy efficacy determined by favorable effect on cognitive ability, cerebral metabolism by FDG-PET, and brain volumes by MRI, and (3) neuropathologic examination of all deaths occurring in these trials.


Design of tables for the presentation and communication of data in ecological and evolutionary biology.
Tables and charts have long been seen as effective ways to convey data. Much attention has been focused on improving charts, following ideas of human perception and brain function. Tables can also be viewed as two-dimensional representations of data; yet, it is only fairly recently that we have begun to apply principles of design that aid the communication of information between the author and reader. In this study, we collated guidelines for the design of data and statistical tables. These guidelines fall under three principles: aiding comparisons, reducing visual clutter, and increasing readability. We surveyed tables published in recent issues of 43 journals in the fields of ecology and evolutionary biology for their adherence to these three principles, as well as author guidelines on journal publisher websites. We found that most of the over 1000 tables we sampled had no heavy grid lines and little visual clutter. They were also easy to read, with clear headers and horizontal orientation. However, most tables did not aid the vertical comparison of numeric data. We suggest that authors could improve their tables by the right-flush alignment of numeric columns typeset with a tabular font, clearly identify statistical significance, and use clear titles and captions. Journal publishers could easily implement these formatting guidelines when typesetting manuscripts.


Optimized damping parameters for empirical dispersion corrections to symmetry-adapted perturbation theory.
Symmetry-adapted perturbation theory (SAPT) has become an invaluable tool for studying the fundamental nature of non-covalent interactions by directly computing the electrostatics, exchange (steric) repulsion, induction (polarization), and London dispersion contributions to the interaction energy using quantum mechanics. Further application of SAPT is primarily limited by its computational expense, where even its most affordable variant (SAPT0) scales as the fifth power of system size [O(N5)] due to the dispersion terms. The algorithmic scaling of SAPT0 is reduced from O(N5)→O(N4) by replacing these terms with the empirical D3 dispersion correction of Grimme and co-workers, forming a method that may be termed SAPT0-D3. Here, we optimize the damping parameters for the -D3 terms in SAPT0-D3 using a much larger training set than has previously been considered, namely, 8299 interaction energies computed at the complete-basis-set limit of coupled cluster through perturbative triples [CCSD(T)/CBS]. Perhaps surprisingly, with only three fitted parameters, SAPT0-D3 improves on the accuracy of SAPT0, reducing mean absolute errors from 0.61 to 0.49 kcal mol-1 over the full set of complexes. Additionally, SAPT0-D3 exhibits a nearly 2.5× speedup over conventional SAPT0 for systems with ∼300 atoms and is applied here to systems with up to 459 atoms. Finally, we have also implemented a functional group partitioning of the approach (F-SAPT0-D3) and applied it to determine important contacts in the binding of salbutamol to G-protein coupled β1-adrenergic receptor in both active and inactive forms. SAPT0-D3 capabilities have been added to the open-source Psi4 software.


Ventricular reconstruction results in improved left ventricular function and amelioration of mitral insufficiency.
Surgical restoration of the left ventricular wall (Dor procedure) has been advocated as a therapy for left ventricular dysfunction due to ischemic cardiomyopathy. This procedure involves placement of an endoventricular patch through a ventriculotomy. We reviewed our series of patients that underwent the Dor procedure within the past 4 years and examined their pre and postoperative ventricular function and mitral valve function. Pre and postoperative ejection fraction and degree of mitral regurgitation were analyzed using the paired Student t-test. We hypothesized that this procedure would result in improved ventricular function and that it would also help improve mitral valve function. Thirty-four patients underwent this procedure, with one death. Of these, 30 patients underwent concomitant coronary artery bypass grafting and 8 patients had mitral intervention (seven had an Alfieri repair of the mitral valve, and one had mitral valve annuloplasty). The average preoperative ejection fraction among these patients was 26.8% (range 10-45%). The postoperative ejection fraction was significantly higher at 35.4% (range 25-52%) (P <.001). We noted an improvement in ejection fraction in 27 patients (82%). We also noted that 21 of 33 patients (64%) had improvement in the degree of mitral regurgitation based on echocardiography data (P <.001). We conclude that the Dor procedure results in improvement in the left ventricular function. Furthermore, we also note that this procedure ameliorates mitral regurgitation in a majority of these patients even in the absence of associated mitral valve procedures, probably due to reduction in the size of the ventricle and improved orientation of the papillary muscles.


Complex Lumbar Spine Fusion for an Elderly Patient Under Spinal Anesthesia.
Spinal anesthesia for spine surgery is an emerging technique. Because of their lack of physiologic reserve, elderly patients are an appealing population for this technique. Unfortunately, the safe limits of spine surgery using spinal anesthesia for the geriatric population are not well defined. The authors describe an elderly patient with severe spine degeneration who elected for a 5-level lumbar spine fusion with spinal anesthesia. Adequate anesthesia was maintained throughout the procedure, which lasted 3 hours and 24 minutes. The patient experienced no perioperative complications. To the authors' knowledge, this is one of the longest spine surgeries using spinal anesthesia. Also, the fusion procedure spans more vertebral levels than previously reported. Further investigation is needed to determine the safety of this technique. [Orthopedics. 2017; 40(5):e915-e917.].


Intrarectal bypass graft in low anterior resection and sigmoid obstruction--an experimental study.
The most common causes for morbidity and mortality in colorectal resections are anastomotic leaks. In low anterior resection, the incidence of anastomotic leakage ranges from 17 to 50%. With the use of the stapler technique, leakage incidence rate remains high and ranges from 10 to 25%. Colostomy formation and closures are associated with considerable morbidity and mortality. Due to the high incidence of anastomotic leakage rate in low anterior resection, and the additional complications of diverting colostomy formation and closure, the use of a rectal stent-intrarectal bypass graft has been instituted. This is carried out by means of a silastic graft, which prevents the fecal stream and gas pressure from coming into contact with the anastomotic site at the low rectum. The efficacy of intrarectal bypass graft was examined in two high-risk surgical situations, the first in very low anterior resection and the other, after early sigmoid obstruction. In both situations the intrarectal bypass graft provided for a safe anastomosis. Even when dehiscence and early obstructions occur, the tube may prevent leakage. This procedure presents effective practical implications which obviate the need for a proximal colostomy formation, thereby eliminating the physical and psychological stress that accompanies colostomies.


Polyphenol-rich fraction of Parquetina nigrescens mitigates dichlorvos-induced neurotoxicity and apoptosis.
Parquetina nigrescens (Afzel.) Bullock of the family Asclepiadaceae is known for its antioxidant effects with wide range of uses in Southwestern Nigeria especially in traditional medicine. This study was undertaken to explore if polyphenol-rich fraction (prf) from P. nigrescens will ameliorate dichlorvos-induced neurotoxicity and apoptosis. The exploration utilized evaluation of markers of oxidative stress, apoptosis and serum acetylcholinesterase (AchE) levels. Forty Wistar rats randomly placed in four groups were utilized for the study. Animals in Group A received corn oil, group B- dichlorvos (16 mg/kg), groups C and D- dichlorvos + 100 and 200 mg/kg prf of P. nigrescens respectively. Markers of oxidative stress, antioxidants and apoptosis were assessed in the serum and brain tissues using biochemical assay and immunohistochemistry. Exposure to dichlorvos caused significant decreases in AchE, catalase, superoxide dismutase, glutathione peroxidase (GPx) and increases in hydrogen peroxide (H2O2) generation and malondialdehyde levels. Histopathology and immunohistochemistry of the cerebellum and cerebrum of rats exposed to dichlorvos revealed greater neurotoxic effects in the cerebellum as well as decreased expressions of AchE with a concomitant increase in Bax (proapototic) compared to prf of P. nigrescens treated rats. This study showed that dichlorvos caused cellular and tissue neurotoxicity by inhibiting AchE activity, induced oxidative stress and apoptosis in rats with prominent effects on the cerebellum than cerebrum. The prf of P. nigrescens showed amelioration of neurotoxicity by its antioxidative and antiapoptotic properties in rats exposed to dichlorvos.


Sequence specific molecular recognition and binding by a GC recognizing Hoechst 33258 analogue to the decadeoxyribonucleotide d-[CATGGCCATG]2: structural and dynamic aspects deduced from high field 1H-NMR studies.
The non-exchangeable and imino proton NMR resonances have been assigned of the 1:1 complex of an analogue 2 of Hoechst 33258 1 bound to the decadeoxyribonuycleotide d-[CATGGCCATG]2 by a combination of NOE difference, COSY and NOESYPH techniques. In contrast to Hoechst 33258 which recognizes 5'-AATT sequences exclusively, analogue 2 possesses structural features designed to permit the recognition of GC sites. The NOESY and 1D-NOE experiments place the drug in the minor groove and it is located on the 5'-CCAT sequence. The orientation of the drug in the groove is such as to place the N-methylpiperazine terminus at a GC site. Cross-correlation peaks in the NOESY experiment show that the DNA duplex retains its right-handed B form, similar to that in the free decamer. Specific NOEs locate the benzoxazole moiety on the 5'-CCAT and are consistent with the pyridine nitrogen forming a new hydrogen bond to G(4)-2NH2 at 5'-CCAT. The drug appears to undergo rotation around the C9-C10 bond, at a rate comparable with NMR time scale, even after binding. Variable temperature 1H-NMR studies established that the DNA is thermally stabilized as a result of the drug binding. The drug binding is a dynamic process involving exchange between the equivalent 5'-CCAT sites at approximately 60s-1 with delta G degree of 65 kJ mol-1 at 308K. The experimental evidence is in accord with a slide-swing mechanism for this process.


Utilization and growth patterns of sacroiliac joint injections from 2000 to 2011 in the medicare population.
The high prevalence of persistent low back pain and growing number of diagnostic and therapeutic modalities employed to manage chronic low back pain and the subsequent impact on society and the economy continue to hold sway over health care policy. Among the multiple causes responsible for chronic low back pain, the contributions of the sacroiliac joint have been a subject of debate albeit a paucity of research. At present, there are no definitive conservative, interventional or surgical management options for managing sacroiliac joint pain. It has been shown that the increases were highest for facet joint interventions and sacroiliac joint blocks with an increase of 310% per 100,000 Medicare beneficiaries from 2000 to 2011. There has not been a systematic assessment of the utilization and growth patterns of sacroiliac joint injections. Analysis of the growth patterns of sacroiliac joint injections in Medicare beneficiaries from 2000 to 2011. To evaluate the utilization and growth patterns of sacroiliac joint injections. This assessment was performed utilizing Centers for Medicare and Medicaid Services (CMS) Physician/Supplier Procedure Summary (PSPS) Master data from 2000 to 2011. The findings of this assessment in Medicare beneficiaries from 2000 to 2011 showed a 331% increase per 100,000 Medicare beneficiaries with an annual increase of 14.2%, compared to an increase in the Medicare population of 23% or annual increase of 1.9%. The number of procedures increased from 49,554 in 2000 to 252,654 in 2011, or a rate of 125 to 539 per 100,000 Medicare beneficiaries. Among the various specialists performing sacroiliac joint injections, physicians specializing in physical medicine and rehabilitation have shown the most increase, followed by neurology with 1,568% and 698%, even though many physicians from both specialties have been enrolling in interventional pain management and pain management. Even though the numbers were small for nonphysician providers including certified registered nurse anesthetists, nurse practitioners, and physician assistants, these numbers increased substantially at a rate of 4,526% per 100,000 Medicare beneficiaries with 21 procedures performed in 2000 increasing to 4,953 procedures in 2011. The, majority of sacroiliac joint injections were performed in an office setting. The utilization of sacroiliac joint injections by state from 2008 to 2010 showed increases of more than 20% in New Hampshire, Alabama, Minnesota, Vermont, Oregon, Utah, Massachusetts, Kansas, and Maine. Similarly, some states showed significant decreases of 20% or more, including Oklahoma, Louisiana, Maryland, Arkansas, New York, and Hawaii. Overall, there was a 1% increase per 100,000 Medicare population from 2008 to 2010. However, 2011 showed significant increases from 2010. The limitations of this study included a lack of inclusion of Medicare participants in Medicare Advantage plans, the availability of an identifiable code for only sacroiliac joint injections, and the possibility that state claims data may include claims from other states. . This study illustrates the explosive growth of sacroiliac joint injections even more than facet joint interventions. Furthermore, certain groups of providers showed substantial increases. Overall, increases from 2008 to 2010 were nominal with 1%, but some states showed over 20% increases whereas some others showed over 20% decreases.


Rapid eye movement sleep measures of Alzheimer's-type dementia patients and optimally healthy aged individuals.
It has been suggested that rapid eye movement (REM) sleep measures may be useful in the differential diagnosis of affective disorders. To determine what changes, if any, of REM measures occur in Alzheimer's dementia we examined the REM sleep of nine control and nine mild, nine moderate, and nine severe dementia subjects with probable Alzheimer's disease (AD). Control and mild and moderate AD groups were screened to exclude major depression. REM latency, REM time, REM activity, and REM density were examined. Results indicated that REM sleep measures are minimally affected by mild dementia. None of the REM sleep variables reported here successfully discriminated mild AD subjects from controls. However, REM time and REM latency were significantly affected in later stages of dementia. Total time in REM and REM latency successfully classified control and moderate-severe AD patients. In addition, the pattern of REM density across the night was also affected by severity of dementia. The results of this study, when compared to published REM measure findings in major depression, indicate that with proper cautions REM sleep measures may prove useful in the differential diagnosis of dementia and depression in geriatric patient populations.


Comprehensive evaluation of urban waterlogging prevention resilience based on the fuzzy VIKOR method: a case study of the Beijing-Tianjin-Hebei urban agglomeration.
The Beijing-Tianjin-Hebei urban agglomeration was used to construct a comprehensive evaluation index system for urban waterlogging prevention and control resilience from five aspects: social resilience, economic resilience, ecological resilience, infrastructure resilience, and institutional resilience. The fuzzy VIKOR method was used to evaluate urban waterlogging prevention and control resilience. The results were analyzed at temporal and spatial scales to reveal regional differences and constraints in urban waterlogging prevention toughness and efficiently locate vulnerable urban areas. The resilience level in most of the Beijing-Tianjin-Hebei region increased during 2015-2019, while that of Beijing, Tianjin, Qinhuangdao, and Handan slightly decreased, indicating that the capacity of these cities to manage waterlogging disasters needs strengthening. The spatial difference in urban waterlogging prevention toughness was significant: Beijing, Tianjin, Handan, Tangshan, Langfang, and Shijiazhuang showed medium and high levels of urban waterlogging prevention toughness; other cities showed low levels. How the expansion speed of the urban scale matches the construction speed of urban waterlogging prevention and control directly affects resilience at all levels. These results support urban waterlogging control and regional integration construction for Beijing-Tianjin-Hebei.


Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma.
Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma. We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5 ml of peripheral blood samples collected from patients using the Canpatrol® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 (IMP3) expression in CTCs were analyzed. CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients (P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features (P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3-positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression. This study demonstrates that the CTCs, especially the IMP3-positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.


Routine sensor-augmented pump therapy in type 1 diabetes: the INTERPRET study.
Sensor-augmented pump (SAP) therapy can improve glycemic control, compared with multiple daily insulin injections or with insulin pump therapy alone, without increasing the risk of hypoglycemia. A 12-month observational study in patients with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII), upon the introduction of continuous glucose monitoring (CGM), was conducted in 15 countries (in Europe and in Israel) to document the real-life use of SAP and assess which variables are associated with improvement in type 1 diabetes management. Data from 263 patients (38% male; mean age, 28.0 ± 15.7 years [range, 1-69 years]; body mass index, 23.3 ± 4.9 kg/m(2); diabetes duration, 13.9 ± 10.7 years; CSII duration, 2.6 ± 3 years) were collected. Baseline mean glycated hemoglobin A1c (HbA1c) was 8.1 ± 1.4%; 82% had suboptimal HbA1c (≥ 7%). The average sensor use for 12 months was 30% (range, 0-94%), and sensor use decreased with time (first 3 months, 37%; last 3 months, 27%). Factors associated with improvement in HbA1c after 12 months in patients with baseline HbA1c ≥ 7% were high baseline HbA1c (P<0.001), older age group (P<0.001), and more frequent sensor use (P = 0.047). Significantly less hospitalization, increased treatment satisfaction, and reduced fear of hypoglycemia were reported after 12 months of SAP. This is the largest and longest multicenter prospective observational study providing real-life data on SAP. These results are consistent with those of controlled trials showing the effectiveness of CGM in pump users.


The effect of a dissolvable hyaluronic acid-based pack on the healing of the nasal mucosa of sheep.
There is a paucity of knowledge about the healing of the nasal respiratory mucosa after endoscopic sinus surgery (ESS). Nasal packs often are placed after ESS in an attempt to reduce adhesions but the effect of these packs on the healing of the nasal mucosa is not known. A standardized normal animal model (the sheep) was used to examine the healing of the nasal epithelium after ESS. A full-thickness wound was created in the nasal mucosa and either packed with a dissolvable hyaluronic acid-based pack or left unpacked to serve as control. The wounded areas were biopsied at 28, 56, 84, and 112 days postinjury and epithelialization, and cilial regeneration was assessed by light microscopy and scanning electron microscopy. The wounds with the dissolvable hyaluronic acid-based packs showed no differences in reepithelialization up to 84 days postwounding. However, a significant increase in reepithelialization was observed on day 84 in packed wounds compared with unpacked controls, indicating an increased rate of healing at that time point. In addition, there was a significant increase in the epithelial height in the packed wounds on day 28, indicating that packing was affecting the epithelial maturity of the mucosa. No significant difference was observed in cilial regeneration between the packed and control wounds. Application of the hyaluronic acid-based nasal packs to wounds after ESS may improve reepithelialization of the nasal mucosa but appears to have minimal effect on reciliation at the time points studied in normal-healing wounds.


Phenolic content of olive oil is reduced in extraction and refining.
Three grades of olive oil and ten vegetable cooking oils were analysed for their phenolic content. It was hypothesised that as olive oil passed through the chemical extraction process, polyphenols would also be removed, thus reducing the antioxidant properties of olive oil. Other commonly used edible vegetable oils were analysed for comparative reasons. Extra virgin olive oil was found to have the greatest amount (48 μg/gram of oil) of polyphenols, when compared with other olive or vegetable oils. No polyphenols were detected in sunflower, walnut, peanut or almond oils. All other oils tested had a polyphenolic content between 2 and 10 μg/gram of oil. The results of the study confirms the above hypothesis that the phenolic content of olive oil is reduced by chemical extraction and refining.


Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs.
To examine the role of polymorphonuclear neutrophils (PMN) and other granulocytes in the pathogenesis of acute lung injury caused by tumor necrosis factor alpha (TNF), we compared the permeability edema and pulmonary histopathology in normal (granulocyte sufficient) guinea pigs and in granulocytopenic guinea pigs treated with TNF. Circulating granulocytes were depleted with cyclophosphamide. Two groups of normal animals were treated with either saline (PMN+/Control) or 1.4 x 10(6) U/kg recombinant human TNF (PMN+/TNF). Three granulocytopenic groups were treated with either saline (PMN-/Control), TNF (PMN-/TNF), or intravenous infusion of 2 x 10(9) E. coli strain J96 (PMN-/Sepsis). We measured the amount of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid and whole lung tissue and the wet/dry lung weight ratio to assess pulmonary transvascular protein flux and edema. We also quantified PMN in BAL fluid and fixed lung tissue. There were no statistically significant differences in any of these parameters between the PMN+/Control, PMN-/Control, or PMN-/TNF groups, except that the PMN+/Control predictably had more PMN/alveolus than the PMN- groups. However, both the PMN+/TNF and the PMN-/Sepsis groups had increased amounts of 125I-labeled albumin in BAL fluid and lung tissue (p less than 0.01) and increased wet/dry lung weight ratios (p less than 0.05), compared to all other groups. Histopathologically, capillary congestion and moderate inflammation were seen in the PMN+/TNF group, and acute inflammation and gross alveolar hemorrhage were seen in the PMN-/Sepsis group.(ABSTRACT TRUNCATED AT 250 WORDS)


Seaweeds rehydration and boiling: Impact on iodine, sodium, potassium, selenium, and total arsenic contents and health benefits for consumption.
Considering the importance of seaweeds for the development of sustainable and innovative food products, this study aimed to characterize the impact of hydrothermal processing on iodine, sodium, potassium, selenium, and arsenic concentrations of four seaweed species (S. latissima, L. digitata, U. pinnatifida, and C. crispus) and on the associated health risks-benefits for consumers. These elements revealed a common pattern for leachable fractions of iodine, total arsenic, and selenium: L. digitata ≥ S. latissima > C. crispus > U. pinnatifida after rehydration and boiling during different periods. The behavior for sodium was: S. latissima > L. digitata > C. crispus > U. pinnatifida, and for potassium: U. pinnatifida > L. digitata > S. latissima > C. crispus. Generally, the species that attained more significant losses were S. latissima and L. digitata. A health-relevant sodium/potassium ratio below 0.7 was found for all species except for U. pinnatifida. In some species, the risk-benefit analysis revealed that high iodine and arsenic levels might promote risks for consumption, even after 20 min boiling, but 5 g of processed U. pinnatifida could contribute to adequate iodine, sodium, potassium, and selenium intakes for all population groups. Standardized processing treatments of seaweeds can open new opportunities for the sector.


Prognostic Association of Major Frailty Domain Trajectories With 5-Year Mortality in Very Old Adults: Results From the PARTAGE Cohort Study.
We aimed to identify trajectories of nutrition, cognitive function, and autonomy over time among very old adults and to assess their impact on mortality. A cohort of subjects aged ≥80 years (in 2007-2008) who were followed for 5 years in 72 Italian and French nursing homes was used for post hoc analyses. Body mass index (BMI; weight (kg)/height (m)2), Mini-Mental State Examination (MMSE) score, and Katz Index of Independence in Activities of Daily Living (ADL) score were assessed at 4 time points. Information on vital status was collected during follow-up. Latent trajectory and Cox models were used. In the 710 subjects included, the mean age at inclusion was 88.0 (standard deviation, 4.8) years, and 78.9% were female. We identified 7 composite trajectories based on BMI, MMSE, and ADL values. As compared with the reference group (trajectory 7-stable overweight; preserved cognitive function and autonomy), 2 trajectories presented increased hazards of dying: trajectory 1 (stable overweight; moderately impaired, then declining, cognitive function and autonomy (adjusted hazard ratio = 1.79, 95% confidence interval (CI): 1.26, 2.55)) and trajectory 6 (stable normal BMI; slight cognitive decline; and moderate, then degrading, loss of autonomy (adjusted hazard ratio = 1.67, 95% CI: 1.15, 2.44)). The C-index was 0.81 (95% CI: 0.72, 0.88). Repeated monitoring of BMI, MMSE score, and ADL in very old adults provides trajectories that produce better prognostic information than simple baseline assessment.


The hexosamine biosynthesis pathway-related gene signature correlates with immune infiltration and predicts prognosis of patients with osteosarcoma.
Osteosarcoma is a malignant bone tumor with poor outcomes affecting the adolescents and elderly. In this study, we comprehensively assessed the metabolic characteristics of osteosarcoma patients and constructed a hexosamine biosynthesis pathway (HBP)-based risk score model to predict the prognosis and tumor immune infiltration in patients with osteosarcoma. Gene expression matrices of osteosarcoma were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. GSVA and univariate Cox regression analysis were performed to screen the metabolic features associated with prognoses. LASSO regression analysis was conducted to construct the metabolism-related risk model. Differentially expressed genes (DEGs) were identified and enrichment analysis was performed based on the risk model. CIBERSORT and ESTIMATE algorithms were executed to evaluate the characteristics of tumor immune infiltration. Comparative analyses for immune checkpoints were performed and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict immunotherapeutic response. Finally, hub genes with good prognostic value were comprehensive analyzed including drug sensitivity screening and immunohistochemistry (IHC) experiments. Through GSVA and survival analysis, the HBP pathway was identified as the significant prognostic related metabolism feature. Five genes in the HBP pathway including GPI, PGM3, UAP1, OGT and MGEA5 were used to construct the HBP-related risk model. Subsequent DEGs and enrichment analyses showed a strong correlation with immunity. Further, CIBERSORT and ESTIMATE algorithms showed differential immune infiltration characteristics correlated with the HBP-related risk model. TIDE algorithms and immune checkpoint analyses suggested poor immunotherapeutic responses with low expression of immune checkpoints in the high-risk group. Further analysis revealed that the UAP1 gene can predict metastasis. IHC experiments suggested that UAP1 expression correlated significantly with the prognosis and metastasis of osteosarcoma patients. When screening for drug sensitivity, high UAP1 expression was suggestive of great sensitivity to antineoplastic drugs including cobimetinib and selumetinib. We constructed an HBP-related gene signature containing five key genes (GPI, PGM3, UAP1, OGT, MGEA5) which showed a remarkable prognostic value for predicting prognosis and can guide immunotherapy and targeted therapy for osteosarcoma.


The Role of Statins in the Management of Nonalcoholic Fatty Liver Disease.
Non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) are the most common causes of elevated liver enzymes in the general population. NASH, and to a lesser extent NAFLD have been associated with increased liver-related, cardiovascular disease (CVD), and allcause mortality. No effective treatment is widely acceptable. The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH. A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH. Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial. Post hoc data from three large prospective randomized clinical trials (n>11, 000) suggest that specific statins (mainly atorvastatin) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function. Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH. Statin treatment may also protect from hepatocellular carcinoma (HCC) related to NAFLD/NASH. Since NAFLD/NASH patients have high CVD risk, they will probably require a statin. Thus, why not select a specific statins (atorvastatin or rosuvastatin, both generic now) that offer a substantial liver- and CVDrelated adverse event reduction? The administration of statins in these patients is as safe as in the general population.


Optimal entry position on the lateral femoral surface for outside-in drilling technique to restore the anatomical footprint of anterior cruciate ligament.
To investigate the optimal starting points for drilling on the lateral femoral condyle for better coverage of the anatomical footprint of the anterior cruciate ligament (ACL) using the outside-in (OI) technique in a single-bundle ACL reconstruction. Femoral tunnel drilling was simulated on three-dimensional bone models from 40 subjects by connecting the centre of the ACL footprint with various points on the lateral femoral surface. The percentage of the femoral footprint covered by apertures of the virtual tunnel sockets with 9 mm diameter was calculated for each tunnel. The mean percentages of the femoral footprint covered by the apertures of the virtual tunnel sockets were significantly higher when drilled at 2 and 3 cm from the lateral epicondyle on a 45° line and a 60° line anterior from the proximal-distal axis than the other points. However, articular cartilage damage was occurred in nine subjects at 3 cm on a 60° line and eight subjects at 3 cm on a 45° line. Posterior wall blowout occurred in five subjects at 3 cm on a 45° line. Thus, OI drilling at 3 cm from the epicondyle has a risk of these complications. During the OI drilling of the femoral tunnel, connecting the centre of the anatomical footprint of the ACL and the entry drilling point at 2 cm from the lateral epicondyle on between the 45° line and the 60° line anterior from the proximal-distal axis provides an oval-shaped socket aperture that covers and restores the native ACL footprint as nearly as possible. III.


Variation of organ position in snakes.
The complex and successful evolutionary history of snakes produced variation in the position and structure of internal organs. Gravity strongly influences hemodynamics, and the impact on structure and function of the cardiovascular system, including pulmonary circulation, is well established. Therefore, we hypothesized that interspecific variation in the position of the heart and vascular (faveolar) lung should exceed that of other internal organs that are less sensitive to gravity. We examined the position of selected internal organs in 72 snakes representing 5 families and 13 species including fully aquatic and scansorial/arboreal species, representing the extremes of gravitational influence. Tests for differences of variance and coefficients of variation largely confirm that interspecific variation in position of the heart and vascular lung generally exceed those of other organs that we measured, particularly posterior organs. The variance of heart position generally exceeded that of more posterior organs, was similar to that of the anterior margin of the vascular lung, and was exceeded by that of the posterior margin of the vascular lung (variance ratio = 0.23). The gravity-sensitive vascular lung exhibited the greatest variation of any organ. Importantly, these findings corroborate previous research demonstrating the influence of gravity on cardiopulmonary morphology. Snakes offer useful model systems to help understand the adaptation of organs to a spectrum of conditions related to diversity of behavior and habitat across a broad range of related taxa.


Coincidence fractional Fourier transform implemented with partially coherent light radiation.
We introduce the coincidence fractional Fourier transform (FRT) implemented with incoherent and partially coherent light radiation. Optical systems for implementing the coincidence FRT are designed. The results show that the visibility and quality of the coincidence FRT of an object are closely related to the light source's transverse size, coherence, and spectral width. As an example, we numerically study the coincidence FRT of a single slit.


Diabetic Retinopathy in the Asia-Pacific.
Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is the leading cause of new cases of blindness in middle-aged and elderly in the Asia-Pacific. It has been estimated that 51% of all those with blindness due to DR globally (n = 424,400) and 56% of those with visual impairment due to DR (2.1 million) come from the Asia-Pacific. Prevalence of DR among those with diabetes ranged from 10% in India to 43% in Indonesia within the Asia-Pacific. Awareness of DR among persons with diabetes ranged from 28% to 84%. Most common modifiable risk factors for DR in the Asia-Pacific were hyperglycemia, blood pressure, dyslipidemia, and obesity. Implementation of systematic screening programs for DR and advancement in telemedicine screening methods have increased patient coverage and cost-effectiveness, though there are still numerous factors impeding screening uptake in the low-middle income regions of the Asia-Pacific. Management and treatment of DR in the Asia-Pacific is mainly limited to traditional laser retinopexy, but it is suboptimal despite new clinical approaches such as use of intravitreal anti.vascular endothelial growth factor and steroids due to limited resources. Further research and data are required to structure a more cost-effective public healthcare program and more awareness-building initiatives to increase the effectiveness of DR screening programs.


Effect of rice cell-derived human granulocyte-macrophage colony-stimulating factor on 5-fluorouracil-induced mucositis in hamsters.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important regulator of the maturation and function of cells in the granulocyte and macrophage lineages, and also plays a significant role in wound healing. In a previous study, we expressed human GM-CSF in rice cells (rice cell-derived human GM-CSF; rhGM-CSF). The purpose of the present study was to evaluate its effect on wound healing in oral mucositis. Oral mucositis was induced in Syrian hamster cheek pouches by 5-fluorouracil treatment and mechanical scratching. Ulcerated areas were treated from days 3 to 14 with an application of 200 µL saline, or of the same volume of a solution containing 0.04, 0.2, or 1 µg/mL rhGM-CSF. Treatment of hamsters with rhGM-CSF reduced the ulcerated areas of the oral mucosa, compared with the control. Early in the healing process, the mucositis tissue layer of the rhGM-CSF-treated group showed significantly decreased myeloperoxidase activity and increased numbers of proliferating cell nuclear antigen (PCNA)-positive cells. Treatment with rhGM-CSF also affected expression of inflammatory cytokines in the ulcerative mucosal tissue. These results demonstrate the efficacy of plant-produced rhGM-CSF in wound healing and have significant implications for the development of rhGM-CSF as a therapeutic agent for ulcerative oral mucositis.


High-precision background correction and artifact suppression for ultrafast spectroscopy by quasi-simultaneous measurements in a split-sample cell.
Alternating acquisition of background and sample spectra is often employed in conventional Fourier-transform infrared spectroscopy or ultraviolet-visible spectroscopy for accurate background subtraction. For example, for solvent background correction, typically a spectrum of a cuvette with solvent is measured and subtracted from a spectrum of a cuvette with solvent and solute. Ultrafast spectroscopies, though, come with many peculiarities that make the collection of well-matched, subtractable background and sample spectra challenging. Here, we present a demountable split-sample cell in combination with a modified Lissajous scanner to overcome these challenges. It allows for quasi-simultaneous measurements of background and sample spectra, mitigating the effects of drifts of the setup and maintaining the beam and sample geometry when swapping between background and sample measurements. The cell is moving between subsequent laser shots to refresh the excited sample volume. With less than 45 μl of solution for 150 μm optical thickness, sample usage is economical. Cell assembly is a key step and covered in an illustrated protocol.


Effect of the exposure to TV food advertisements on the consumption of foods by mothers and children.
Foods advertised were recorded in 2 television (TV) channels. The present article studies the association between products advertised and those consumed by mothers and children. A total of 365 mothers and their children were assessed. A positive correlation was observed between the food advertisements that the mothers recalled and the frequency of TV food advertisements (Rho = 0.44, P = 0.03). A positive correlation was found between the frequency of the foods advertised on TV and the consumption of these by the mothers (r = 0.73, P = 0.0001) and their children (Rho = 0.66, P = 0.0001). These results suggest that TV advertisements influence the food choices of mothers and children.


Prevention of ultraviolet damage to the dermis of hairless mice by sunscreens.
To assess the ability of sunscreens to protect connective tissue from actinic damage, hairless mice were irradiated with Westinghouse FS20 sunlamps thrice weekly for 30 weeks. Each exposure, consisting mainly of UV-B and the less energetic UV-A, was approximately 6 human minimal erythema doses under these lights. One group of animals received irradiation only. The other 2 groups were treated, prior to irradiation, with sunscreens of either low or high sun protection factors (SPF 2 and SPF 15, respectively). Skin biopsies were taken at 10-week intervals and were stained with various histochemical stains to reveal changes in the dermis. The unprotected, irradiated animals showed a great increase in the following: reticulin fibers, elastic fibers to the extent of elastosis, neutral and acid mucopolysaccharides and melanin production. The SPF 15 sunscreen completely prevented these changes. The SPF 2 sunscreen was less effective. These effects were substantiated by ultrastructural examination of the tissues by electron microscopy. A surprising histologic finding was the repair capability of the dermis in the post-irradiation period.


A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture.
Fed-batch animal cell culture is the most common method for commercial production of recombinant proteins. However, higher cell densities in these platforms are still limited due to factors such as excessive ammonium production, lactic acid production, nutrient limitation, and/or hyperosmotic stress related to nutrient feeds and base additions to control pH. To partly overcome these factors, we investigated a simple method to reduce both ammonium and lactic acid production-termed Lactate Supplementation and Adaptation (LSA) technology-through the use of CHO cells adapted to a lactate-supplemented medium. Using this simple method, we achieved a reduction of nearly 100% in lactic acid production with a simultaneous 50% reduction in ammonium production in batch shaker flasks cultures. In subsequent fed-batch bioreactor cultures, lactic acid production and base addition were both reduced eight-fold. Viable cell densities of 35 million cells per mL and integral viable cell days of 273 million cell-days per mL were achieved, both among the highest currently reported for a fed-batch animal cell culture. Investigating the benefits of LSA technology in animal cell culture is worthy of further consideration and may lead to process conditions more favorable for advanced industrial applications.


A comparison of Er,Cr:YSGG laser to minimally invasive surgical technique in the treatment of intrabony defects: Twelve-month results of a multicenter, randomized, controlled study.
The purpose of this publication is to report on the 12-month clinical and radiographic results comparing the surgical use of the Er,Cr:YSGG laser (ERL) and minimally invasive surgical technique (MIST) for the treatment of intrabony defects in subjects with generalized periodontitis stage III, grade B. Fifty-three adult subjects (29 females and 24 males; 19-73 years) with 79 intrabony defects were randomized following scaling and root planing (SRP) to receive ERL monotherapy (n = 27) or MIST (n = 26). Fifty subjects completed the study. Recession (REC), probing depth (PD), clinical attachment level (CAL), treatment time, and standardized radiographs were assessed and compared for each treatment group. Clinical measurements were recorded at baseline, 4-6 weeks following SRP, and 6 and 12 months following surgical therapy. Radiographic results were compared to baseline at 6 and 12 months following surgical therapy. The following primary and secondary outcome variables were non-inferior with the following margins: CAL with a non-inferiority margin of 0.7 mm (p = 0.05), PD with a non-inferiority margin of 0.7 mm (p = 0.05), and REC with a non-inferiority margin of 0.4 mm (p = 0.05). Standardized radiographs suggest similar bone fill of 1.14 ± 1.73 mm for MIST and 1.12 ± 1.52 mm for ERL. This is the first multicenter, randomized, masked, and controlled study demonstrating the ERL is not inferior to MIST at 12 months in terms of clinical outcomes and similar to MIST in terms of radiographic bone fill for the surgical treatment of intrabony defects.


Alteration of substrate regulation patterns in glutamate dehydrogenase by enzyme immobilization.
Substrate regulation patterns were changed by covalent binding of bovine liver glutamate dehydrogenase via primary amino groups to CNBr- and CH-activated Sepharose 4B. Lineweaver-Burk plots show that the NAD activation region changed from being abrupt to elongated when the enzyme was immobilized to either support. The elongated region contains two inflection points and resembles substrate activation of several other allosteric oligomers. Glutamate induced varying degrees of abrupt activation in immobilized glutamate dehydrogenase and inhibited the native enzyme. This activation is characterized by an activation threshold, an increase in the apparent dissociation constant, and a correlation between the apparent rate constant and the degree of activation. These three features characterize other glutamate dehydrogenase systems.


Reversible deficits in apical transporter trafficking associated with deficiency in diacylglycerol acyltransferase.
Deficiency in diacylglycerol acyltransferase (DGAT1) is a rare cause of neonatal diarrhea, without a known mechanism or in vitro model. A patient presenting at our institution at 7 weeks of life with failure to thrive and diarrhea was found by whole-exome sequencing to have a homozygous DGAT1 truncation mutation. Duodenal biopsies showed loss of DGAT1 and deficits in apical membrane transporters and junctional proteins in enterocytes. When placed on a very low-fat diet, the patient's diarrhea resolved with normalization of brush border transporter localization in endoscopic biopsies. DGAT1 knockdown in Caco2-BBe cells modeled the deficits in apical trafficking, with loss of apical DPPIV and junctional occludin. Elevation in cellular lipid levels, including diacylglycerol (DAG) and phospholipid metabolites of DAG, was documented by lipid analysis in DGAT1 knockdown cells. Culture of the DGAT1 knockdown cells in lipid-depleted media led to re-establishment of occludin and return of apical DPPIV. DGAT1 loss appears to elicit global changes in enterocyte polarized trafficking that could account for deficits in absorption seen in the patient. The in vitro modeling of this disease should allow for investigation of possible therapeutic targets.


Experimental meningococcal septicemia. Effect of heparin therapy.
The pathogenesis of experimental meningococcal septicemia and the efficacy of heparin sodium therapy were evaluated by inoculating rabbits intraperitoneally with type B meningococci in mucin. Half the rabbits died, and the respiratory distress and circulatory failure that occurred during the terminal phase of the disease were associated with diffuse pulmonary capillary and venular thrombosis and with renal glomerular fibrin deposition. Platelet and leukocyte counts and plasma fibrinogen levels decreased in all rabbits, and prothrombin and partial thromboplastin times were prolonged. Pretreatment with heparin sodium diminished intravascular fibrin deposition but failed to prevent the pulmonary microthrombi and did not either reduce the mortality or improve the survival time. We conclude that death in meningococcal septicemia is due to widespread thrombosis of the pulmonary microcirculation. The disease is complicated by diffuse intravascular coagulation, which can be controlled with heparin sodium but which is not immediately life-threatening.


Global epidemiology of sporotrichosis.
Sporotrichosis is an endemic mycosis caused by the dimorphic fungus Sporothrix schenckii sensu lato. It has gained importance in recent years due to its worldwide prevalence, recognition of multiple cryptic species within the originally described species, and its distinctive ecology, distribution, and epidemiology across the globe. In this review, we describe the current knowledge of the taxonomy, ecology, prevalence, molecular epidemiology, and outbreaks due to S. schenckii sensu lato. Despite its omnipresence in the environment, this fungus has remarkably diverse modes of infection and distribution patterns across the world. We have delved into the nuances of how sporotrichosis is intimately linked to different forms of human activities, habitats, lifestyles, and environmental and zoonotic interactions. The purpose of this review is to stimulate discussion about the peculiarities of this unique fungal pathogen and increase the awareness of clinicians and microbiologists, especially in regions of high endemicity, to its emergence and evolving presentations and to kindle further research into understanding the unorthodox mechanisms by which this fungus afflicts different human populations.


Identification of adaptive mutations in the influenza A virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.
The NS1 protein of influenza A virus (IAV) is a multifunctional virulence factor. We have previously characterized gain-of-function mutations in the NS1 protein arising from the experimental adaptation of the human isolate A/Hong Kong/1/1968(H3N2) (HK) to the mouse. The majority of these mouse adapted NS1 mutations were demonstrated to increase virulence, viral fitness, and interferon antagonism, but differ in binding to the post-transcriptional processing factor cleavage and polyadenylation specificity factor 30 (CPSF30). Because nuclear trafficking is a major genetic determinant of influenza virus host adaptation, we assessed subcellular localization and host gene expression of NS1 adaptive mutations. Recombinant HK viruses with adaptive mutations in the NS1 gene were assessed for NS1 protein subcellular localization in mouse and human cells using confocal microscopy and cellular fractionation. In human cells the HK wild-type (HK-wt) virus NS1 protein partitioned equivalently between the cytoplasm and nucleus but was defective in cytoplasmic localization in mouse cells. Several adaptive mutations increased the proportion of NS1 in the cytoplasm of mouse cells with the greatest effects for mutations M106I and D125G. The host gene expression profile of the adaptive mutants was determined by microarray analysis of infected mouse cells to show either high or low extents of host-gene regulation (HGR or LGR) phenotypes. While host genes were predominantly down regulated for the HGR group of mutants (D2N, V23A, F103L, M106I+L98S, L98S, M106V, and M106V+M124I), the LGR phenotype mutants (D125G, M106I, V180A, V226I, and R227K) were characterized by a predominant up regulation of host genes. CPSF30 binding affinity of NS1 mutants did not predict effects on host gene expression. To our knowledge this is the first report of roles of adaptive NS1 mutations that impact intracellular localization and regulation of host gene expression.


Ultraviolet light and melanoma.
Melanoma is a clinically heterogeneous disease, and current strategies for treatment of the primary tumour are based on pathological criteria alone. In the recent past, several DNA-sequencing and RNA-sequencing studies of primary and advanced melanoma samples have identified unique relationships between somatic mutations, genomic aberrations, and the genetic fingerprint of ultraviolet radiation (UVR). The recurrent patterns of genomic alterations reveal different disease pathways, drug targets and mechanisms limiting drug response. Here, we examine the known associations between the molecular categories of melanoma and the multidimensional UVR damage. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Measuring time in buprenorphine treatment stages among people with HIV and opioid use disorder by retention definition and its association with cocaine and hazardous alcohol use.
We use a novel, longitudinal approach to describe average time spent in opioid use disorder (OUD) cascade of care stages for people with HIV (PWH) and with OUD, incorporating four definitions of treatment retention. Using this approach, we describe the impact of cocaine or hazardous alcohol use on time spent retained on buprenorphine. We followed PWH with OUD enrolled in the Johns Hopkins HIV Clinical Cohort from their first buprenorphine treatment episode between 2013 and 2020. We estimated 4-year restricted mean time spent on buprenorphine below buprenorphine retention threshold, on buprenorphine above retention threshold, off buprenorphine and in HIV care, loss to follow-up, and death. Retention definitions were based on retention threshold (180 vs 90 days) and allowable treatment gap (7 vs 30 days). Differences in 2-year restricted mean time spent retained on buprenorphine were estimated for patients with and without cocaine or hazardous alcohol use. The study sample (N = 179) was 63% male, 82% non-Hispanic Black, and mean age was 53 (SD 8) years. Patients spent on average 13.9 months (95% CI 11.4, 16.4) on buprenorphine over 4 years. There were differences in time spent retained on buprenorphine based on the retention definition, ranging from 6.5 months (95% CI 4.6, 8.5) to 9.6 months (95% CI 7.4, 11.8). Patients with cocaine use spent fewer months retained on buprenorphine. There were no differences for patients with hazardous alcohol use. PWH with OUD spend relatively little time receiving buprenorphine in their HIV primary care clinic. Concurrent cocaine use at buprenorphine initiation negatively impact time on buprenorphine.


Metformin enhances the cytotoxicity of 5-aminolevulinic acid-mediated photodynamic therapy in vitro.
The biguanide metformin is a drug widely used for the treatment of type 2 diabetes. Metformin enhances the cytotoxicity of chemotherapy by promoting the adenosine monophosphate-activated protein kinase (AMPK) autophagy signaling pathway. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), leads to apoptosis when PpIX accumulates in the mitochondria, and also leads to autophagy through activation of AMPK. In the present study, the effect of metformin in combination with 5-ALA-PDT was evaluated in vitro in KLN205 lung cancer cells. At a fluence of 5 J/cm2, 5-ALA-PDT in combination with 5 mM metformin exhibited significantly increased cytotoxicity compared with that observed with 0 and 0.1 mM metformin (P=0.0197 and P=0.0423, respectively). The cells treated with 5-ALA-PDT and metformin exhibited condensation of nuclear chromatin and the presence of autophagosomes. These results indicate that apoptosis and autophagy occur in KLN205 cells following combined treatment with 5-ALA-PDT and metformin. The results from the present study are the first to indicate, to the best of our knowledge, that metformin potentiates the efficacy of 5-ALA-PDT.


Quality of life and social environment as reported by Chinese immigrants with non-insulin-dependent diabetes mellitus.
Non-insulin-dependent diabetes mellitus (NIDDM) has been associated with stressful events such as immigration. The purpose of this paper is to report a pilot study that tested translated and back-translated instruments to ascertain factors related to diabetes management in a group of Chinese immigrants with diabetes. The descriptive, cross-sectional design included a convenience sample of 30 Chinese immigrants who had been diagnosed with NIDDM for at least 1 year. Consenting participants completed paper- and-pencil questionnaires (Diabetes Family-Behavior Checklist II, Diabetes Quality of Life, and MDRTC Knowledge Test) that had been translated and back-translated into Chinese and returned them in stamped, self-addressed envelopes. Results indicated that most of the scale and subscale reliabilities were similar to those published previously. Study participants had received limited diabetes education, reported many problems managing diabetes, especially in terms of social and vocational issues, and reported dissatisfaction with their quality of life. Diabetes-related family supportive behaviors were rated positively indicating the importance of including family members in educational programs.


Stent fracture associated with drug-eluting stents: clinical characteristics and implications.
To evaluate the clinical characteristics and implications of stent fracture in drug-eluting stents. Approximately 2.5 million drug-eluting stents are implanted every year worldwide. In 10 randomized controlled trials involving 2,602 patients, no incidence of stent fracture was recognized or reported. From April 2003 to December 2005, 2,728 patients underwent drug-eluting stenting. The angiograms of all 530 patients who underwent repeat angiography were analyzed to identify the presence of stent fracture. We then documented the incidence of adverse events associated with drug-eluting stent fracture and systematically analyzed the clinical, procedural, and structural factors, which might predispose to stent fracture. Stent fracture was identified in 10 patients. None of these fractures were detectable at the time of stent placement. The median time interval from stent implantation to detection of fracture at repeat angiography was 226 days (range, 7-620 days). Adverse clinical outcomes associated with stent fracture occurred in 7 patients (6 patients had binary restenosis and 1 patient had stent thrombosis), all necessitating repeat intervention. Analysis of potential predisposing clinical, procedural, and structural factors revealed that 4 patients had excessive tortuosity in the proximal segment, and overlapping stents were used in 5 cases. All fractures occurred in sirolimus-eluting stents. Stent fracture may represent a new potential mechanism of restenosis and stent thrombosis in drug-eluting stents. Predisposing clinical and procedural factors may be vessel tortuosity and use of overlapping stents. The most important predisposing factor, however, may be stent structure, since all fractures occurred in sirolimus-eluting stents.


Regulation of NF-kappaB-dependent gene expression by the POU domain transcription factor Oct-1.
Maintenance of the cells of the vessel wall in a quiescent state is an important aspect of normal vascular physiology. Transcriptional repressors are widely believed to regulate this process, yet the exact factors involved and the mechanism of repression are not known. Here, we report that the POU domain transcription factor Oct-1 represses the expression of E-selectin and vascular cell adhesion molecule (VCAM-1), two cytokine-inducible, NF-kappaB-dependent endothelial-leukocyte adhesion molecules that participate in the leukocyte recruitment phase of the inflammatory response. Co-transfection and microinjection studies demonstrate that Oct-1 blocks tumor necrosis factor alpha-stimulated E-selectin and VCAM-1 expression. Gene expression arrays indicate that control of tumor necrosis factor alpha-induced, NF-kappaB-dependent gene expression by Oct-1 is promoter-specific. A DNA-binding mutant of Oct-1 represses NF-kappaB-dependent reporter gene expression. Biochemically, Oct-1 interacts with p65, suggesting that Oct-1 is involved in the regulation of NF-kappaB transactivation function. NF-kappaB-dependent gene expression is more pronounced in Oct-1-deficient than in wild-type murine embryonic fibroblasts, and reintroduction of human Oct-1 abolishes these differences. Finally, the cytokine interleukin-6 induces Oct-1 gene expression, providing a biologically relevant means by which NF-kappaB-dependent gene expression can be selectively reverted by Oct-1 to quiescent levels.


Molecular Characterization of Corynebacterium diphtheriae Outbreak Isolates, South Africa, March-June 2015.
In 2015, a cluster of respiratory diphtheria cases was reported from KwaZulu-Natal Province in South Africa. By using whole-genome analysis, we characterized 21 Corynebacterium diphtheriae isolates collected from 20 patients and contacts during the outbreak (1 patient was infected with 2 variants of C. diphtheriae). In addition, we included 1 cutaneous isolate, 2 endocarditis isolates, and 2 archived clinical isolates (ca. 1980) for comparison. Two novel lineages were identified, namely, toxigenic sequence type (ST) ST-378 (n = 17) and nontoxigenic ST-395 (n = 3). One archived isolate and the cutaneous isolate were ST-395, suggesting ongoing circulation of this lineage for >30 years. The absence of preexisting molecular sequence data limits drawing conclusions pertaining to the origin of these strains; however, these findings provide baseline genotypic data for future cases and outbreaks. Neither ST has been reported in any other country; this ST appears to be endemic only in South Africa.


[INTERRELATIONS BETWEEN MICROALBUMINURIA AND RENAL FUNCTION WITH CONTRACTILE ABILITY OF LEFT VENTRICLE IN CARDIORENAL SYNDROME PATIENTS].
Chronic kidney disease (CKD) increases the risk of all-cause mortality and cardiovascular disease as well as progression to end stage kidney failure. The relationship of glomerular filtration rate (GFR) and albuminuria with clinical outcomes in the general population are revealed. This allows to present levels of GFR and microalbuminuria (MA), which increases the risk of mortality. Renal dysfunction, which revealed by the level of GFR and creatinine, can have definite role in hemodynamic changes and heart failure progression. For mentioning the interaction of cardiovascular and renal diseases the cardiorenal syndrome (CRS) term was introduced, with its classification on 5 types, according to the presence of acute/chronic heart failure and primary/secondary origination of heart and kidney injury. We study interrelations between echocardiographic data of left ventricular remodeling, MA level and degree of renal dysfunction in 115 patients with CRS. MA was measured with diagnostic strips, contractile function of left ventricle (LV) - by echocardiography and GFR was assessed by Cocroft-Gault method. The association between MA with decreased GFR and elevated creatinine levels and its connection with increased LV myocardial mass and preclinical disturbances of LV systolic function was revealed. We determined direct correlation between MA and myocardial mass index and indirect - between ejection fraction of LV and MA. Obtained data allow to mention the level of MA (25,4±5,8 ng/ml) in which there is more probability of LV contractile functional changes, which will allow early prediction and prevention of CRS progression and pathogenetically approved pharmacotherapy organization in this category patients.


Medialization Laryngoplasty After Injection Augmentation.
This study aims to assess the effect of vocal fold injection augmentation (IA) on subsequent medialization laryngoplasty (ML). A retrospective cohort study with follow-up telephone survey was carried out. Clinical records of patients with unilateral vocal fold paralysis or paresis (VFP) who underwent ML between April 2006 and March 2015 were reviewed. Patients who underwent IA before ML were compared with patients who did not, with respect to demographic information, symptoms, Voice Handicap Index-10 (VHI-10), etiology of VFP, and revision rate. Among patients undergoing IA, the effects of injection material and of interval from IA to ML on revision rate were assessed. Follow-up telephone surveys were conducted to evaluate long-term outcomes using VHI-10 and a condition-specific questionnaire. One hundred thirty-five patients (70 male:65 female) with vocal fold paralysis (125) or paresis (10) underwent ML (96 left:39 right). Sixty-six (48.9%) patients underwent concurrent arytenoid adduction. Fourteen (10.4%) patients required revision. Fifty-six (41.5%) patients had prior IA; five (8.9%) patients underwent revision. Seventy-nine (58.5%) patients did not have IA; nine (11.4%) patients required revision (P = 0.78). Neither augmentation material nor length of interval between last IA and ML affected the revision rate (P = 1.00; P ≥ 0.11 for all tested intervals, respectively). No difference in follow-up VHI-10 score was found between patients who had IA before ML and patients who had not (P = 0.73). IA does not appear to affect the revision rate or long-term outcome of subsequent ML.


Nonlinear dynamics, rectification, and phase locking for particles on symmetrical two-dimensional periodic substrates with dc and circular ac drives.
We investigate the dynamical motion of particles on a two-dimensional symmetric periodic substrate in the presence of both a dc drive along a symmetry direction of the periodic substrate and an additional circular ac drive. For large enough ac drives, the particle orbit encircles one or more potential maxima of the periodic substrate. In this case, when an additional increasing dc drive is applied in the longitudinal direction, the longitudinal velocity increases in a series of discrete steps that are integer multiples of a omega/(2 pi), where a is the lattice constant of the substrate. Fractional steps can also occur. These integer and fractional steps correspond to distinct stable dynamical orbits. A number of these phases also show a rectification in the positive or negative transverse direction where a nonzero transverse velocity occurs in the absence of a dc transverse drive. We map out the phase diagrams of the regions of rectification as a function of ac amplitude, and find a series of tongues. Most of the features, including the steps in the longitudinal velocity and the transverse rectification, can be captured with a simple toy model and by arguments from nonlinear maps. We have also investigated the effects of thermal disorder and incommensuration on the rectification phenomena, and find that for increasing disorder, the rectification regions are gradually smeared and the longitudinal velocity steps are no longer flat but show a linearly increasing velocity.


Healthcare Service Needs of Orphans and Vulnerable Children in Orphanages and Barriers Caregivers face in meeting their Healthcare Service Needs: A Mixed Method Research.
Poor health and well-being among orphans and vulnerable children (OVC) in orphanages has been documented in literature, and evidence has shown an association between access to healthcare and well-being among this population. This study assessed the healthcare service needs of OVC and explored the barriers their caregivers face in meeting their healthcare service needs using a mixed method research approach. The study utilized a multi-stage sampling technique in selecting 384 OVC and 14 caregivers that participated in the study. Data were collected using pre-tested questionnaire and interview guide. The quantitative data were analyzed using Statistical Product and Service Solutions (SPSS) version 23, while the qualitative data were analyzed using thematic and content analysis. The result of the study shows that regular health assessment while in the orphanage tops the list of health services needed by OVC; this was followed by health assessment before or during admission into orphanages and facility visits for management of common illness by health professionals while health education for the children and caregivers ranked third. Mental healthcare was the least need reported by the children. From the caregivers' perspectives, financial, structural and psychological barriers emerged as major themes for barriers faced in meeting the healthcare service needs of OVC. The study concluded that OVC are mainly in need of regular health assessment and treatment of common ailments during facility visits by health professionals. The study further shows that caregivers face significant barriers in meeting the healthcare service needs of OVC.


The Cross-talk between Tristetraprolin and Cytokines in Cancer.
Cytokines are small secreted proteins serving as vital mediators that mediate the host immune responses. Transcription and post-transcription play a critical role in cytokine expression through the regulation of message RNA (mRNA) cytoplasmic localization, translation initiation and decay. Researches have been conducted to reveal regulatory mechanisms of cytokines production in cells involved in cancer. AU-rich element (ARE) can regulate the degradation and translation of mRNA by connecting with specific ARE binding proteins. It is now clear that tristetraprolin (TTP), as the most common ARE binding protein, negatively regulates many aspects of the cytokines through binding to the AREs in the 3'-untranslated region (3'UTR) of mRNA. Furthermore, some certain cytokines have an impact on TTP expression and function. Therefore, the cross-regulation between cytokines and TTP has come into sight. The complicated regulatory networks between cytokines and TTP are closely related to tumorigenesis. In this review, we summarize specific regulatory mechanisms of cytokine mRNAs. We focus on how TTP negatively regulates inflammatory and oncogenic cytokines expression after combining with AREs, we also pay attention to some cytokines mediating the expression of TTP and their cross-talk in various cancers in detail.


Progression to Dementia or Reversion to Normal Cognition in Mild Cognitive Impairment as a Function of Late-Onset Neuropsychiatric Symptoms.
Mild cognitive impairment (MCI) is an at-risk state for dementia; however, not all individuals with MCI transition to dementia, and some revert to normal cognition (NC). Here, we investigate whether mild behavioral impairment (MBI), the late-life onset of persistent neuropsychiatric symptoms (NPS), improves the prognostic specificity of MCI. Participants with MCI from the National Alzheimer's Coordinating Center Uniform Data Set were included. NPS were operationalized with the Neuropsychiatric Inventory Questionnaire to identify participants without NPS and those with MBI (persistent, late-onset NPS). Individuals with late-onset NPS not meeting the MBI persistence criterion (NPS_NOT_MBI) were retained for secondary analyses. Progression to dementia, stable MCI, and reversion to NC after 3 years of follow-up were defined per National Institute on Aging-Alzheimer's Association and Petersen criteria. The primary sample consisted of 739 participants (NPS- n = 409 and MBI+ n = 330; 75.16 ± 8.6 years old, 40.5% female). After 3 years, 238 participants (33.6%) progressed to dementia, and 90 (12.2%) reverted to NC. Compared to participants without NPS, participants with MBI were significantly more likely to progress to dementia (adjusted odds ratio [AOR] 2.13, 95% CI 1.52-2.99), with an annual progression rate of 14.7% (vs 8.3% for participants with MCI without NPS). Compared to participants without NPS, participants with MBI were less likely to revert to NC (AOR 0.48, 95% CI 0.28-0.83, 2.5% vs 5.3% annual reversion rate). The NPS_NOT_MBI group (n = 331, 76.5 ± 8.6 years old, 45.9% female) were more likely to progress to dementia (AOR 2.18, 95% CI 1.56-3.03, 14.3% annual progression rate) but not less likely to revert to NC than those without NPS. Accordingly, both NPS_NOT_MBI and MBI+ participants had lower Mini-Mental State Examination scores than NPS- participants after 3 years. Late-onset NPS improve the specificity of MCI as an at-risk state for progression to dementia. However, only persistent late-onset NPS are associated with a lower likelihood of reversion to NC, with transient NPS (i.e., NPS_NOT_MBI) not differing from the NPS- group. Clinical prognostication can be improved by incorporating late-onset NPS, especially those that persist (i.e., MBI), into risk assessments. Clinical trials may benefit from enrichment with these higher-risk participants with MCI.


Adverse pregnancy outcomes after a false-positive second trimester serum screen for Down syndrome in Thai pregnant women.
To determine whether a false-positive second trimester serum screen for Down syndrome in Thai pregnant women is predictive of adverse pregnancy outcomes. The relationship between adverse pregnancy outcomes in women and a false-positive screening for Down syndrome was investigated in a case-control study. The Double-marker maternal serum screening for Down syndrome (alpha-fetoprotein and free beta-hCG) was performed on Thai pregnant women between 14 and 21 weeks 'gestation at Charoenkrung Pracharuk Hospital from March 1998 to August 2002. The pregnancy outcomes of 165 women having false positive serum screening (risk ratio at least 1.270; study group) were compared to the outcomes of 165 control patients having negative serum screening results (control group). The outcome indices analyzed were preterm delivery, low birth weight newborn, small-for-gestational age newborn, preeclampsia, placenta previa, and fetal death. The incidence of adverse pregnancy outcomes was 18.2% in the study group and 15.2% in the control group (odds ratio = 1.244; 95% confidence interval = 0.696, 2.225; p = 0.46). Women in the study group delivered at a significantly lower birth weight of newborns than women in the control group did (3088.1 +/- 543.9 versus 3229.1 +/- 454.6 g, respectively; p = 0.011). No significant differences in adverse outcomes was discovered after the comparisons between the study group and the control group. preterm delivery 11 of 165 (6.6%) versus 5 of 165 (3%), p = 0.124; low birth weight newborn 11 of 165 (6.6%) versus 6 of 165 (3.6%), p = 0.213; small for gestational age newborn 4 of 165 (2.4%) versus 0 of 165 (0%), p = 0.123; preeclampsia 16 of 165 (9.7%) versus 12 of 165 (7.3%), p = 0.429; placenta previa 4 of 165 (2.4%) versus 4 of 165 (2.4%), p=1; fetal death 1 of 165 (0.6%) versus 0 of 165 (0%), p=1. The present findings revealed no apparent increase in the adverse pregnancy outcomes analyzed in women with false positive Down syndrome screening test.


Early and mid-term results of coronary endarterectomy: Influence of cardiopulmonary bypass and surgical techniques.
Coronary endarterectomy (CE) may be a good option for complete revascularization of diffuse coronary artery diseases, but it has not been widely used because the outcomes have not been definitively identified. This study aims to evaluate the mid-term clinical results of CE and compare the outcomes according to the use of cardiopulmonary bypass (CPB) and the surgical technique used. Between 2004 and 2014, 69 cases of CE were performed in 64 patients. We divided the pa-tients into two groups: 1) on-pump coronary artery bypass with coronary endarterectomy (ONCAB-CE) versus off-pump coronary artery bypass with coronary endarterectomy (OPCAB-CE), and 2) "open" versus "closed" surgical techniques. Operative mortality and major morbidity, were investigated includ-ing perioperative myocardial infarction (PMI), and overall survival. Operative mortality was 4.7% (3/64), and no PMI was observed in the study. No statistical differences in operative mortality rate between the ONCAB-CE and OPCAB-CE groups were found (3.1% vs. 6.2%, p = 1.0) or between open versus closed techniques (6.7% vs. 2.9%, p = 0.6). The incidence of major morbidity including cerebrovascular accident, atrial fibrillation, acute renal failure, mediastinitis, respiratory complications, and bleeding was comparable between all groups. There were seven late mortalities, and no differences were found in overall survival rate between all groups. Coronary endarterectomy appears to be a safe option for patients with diffuse coronary artery disease, regardless of whether CPB or a specified selection of surgical techniques are used.


[Effect of cyclophosphamide on ovarian function in patients with systemic lupus erythematosus in childbearing age].
Objective: Serum anti Müllerian hormone (AMH) was used to evaluate the effect of cyclophosphamide (CTX) on ovarian function in female patients with systemic lupus erythematosus (SLE). Methods: A total of 121 female patients who were 18-50 years old with normal menstruation were selected. Among them, 54 patients were treated with CTX as the study group and the remaining 67 cases as the control group. Before and after treatment for 6 months, the clinical characteristics, menstruation and AMH level of all patients were recorded and detected. At the same time, the method of using CTX and the cumulative measurement are recorded. Results: (1) Before treatment, there was no significant difference in AMH and mean age, duration of disease and SLEDAI score between the CTX treatment group and the control group. The renal injury in the CTX treatment group (44.4%) was higher than that of the control group (34.3%), and the difference was statistically significant (P<0.05). (2) After 6 months of treatment, the AMH of group CTX decreased from (2.39±1.58) μg/L to (1.56±1.42) μg/L, and the difference was statistically significant (P<0.01). But there was no significant change in the control group. In 54 cases of CTX treatment group, 23 cases (42.6%) had different degree of menstrual abnormalities, while 67 cases had only 8 cases (11.9%) in the control group. Moreover, the AMH level of 31 cases with abnormal menstruation was (0.95±0.59) μg/L, which was significantly lower than that of the other 90 normal cases (2.36±1.58) μg/L. (3) In 54 cases of CTX treatment group, the cumulative dose of CTX was less than 3 g in 14 cases, 33 cases of 3-6 g, 7 cases greater than 6 g. AMH was all were lower than those before treatment. But there was a statistical difference between the 3 g group and 3-6 g group before treatment, and there were statistical differences between the groups. Conclusion: CTX can damage ovarian function in women of childbearing age SLE. Low dose intravenous CTX may have less damage. Serum AMH can be used to monitor ovarian function in patients with SLE and to guide individualized treatment.


Real-time analysis of arc-induced Long Period Gratings under gamma irradiation.
In this paper, we present a comparative experimental and theoretical study on gamma radiation sensitivity of Long Period Gratings (LPGs), fabricated by electric arc discharge technique, as monitored in three single mode optical fibers supplied by different manufacturers. A real-time measurement of LPGs' wavelength shift was performed until a total dose of 35 kGy was reached, with average dose rate of 0.18 kGy/h, the irradiation being done at room temperature. In one case, a maximum radiation sensitivity of 1.34 nm/kGy was recorded for doses up to 0.5 kGy. Moreover, by combining experimental results with numerical simulations, it was found that changes occurred in the core refractive index of the irradiated optical fibers up to 2.5 ∙ 10-5. The increase of the core thermo-optic coefficient up to 1.5 ∙ 10-8/°C was observed as well.


Brachytherapy in the treatment of bile duct cancer - a tough challenge.
The majority of patients with bile duct cancer are diagnosed with clinically advanced disease. Most of these patients have a short life expectancy and are treated with palliative aim. Most patients present with locally advanced or metastatic disease, which is not amenable to surgical resection, resulting in poor survival. Adjuvant or definitive radiotherapy, with or without chemotherapy, is therefore used in many centers worldwide for better local control, and with the expectation that it will have a favorable effect on survival. However, the lack of appropriate prospective trials, as well as the small size of the published series and their retrospective nature, has produced insufficient evidence for the best treatment for these patients. Intraluminal brachytherapy is an important component in the multimodality approach to bile duct cancers. The objective of this treatment is to deliver a high local dose of radiation to the tumor while sparing surrounding healthy tissues. The treatment can be safely adapted for right and left hepatic duct, and for common bile duct lesions. Brachytherapy plays a limited but specific role in definitive treatment with curative intent in selected cases of early disease, as well as in the postoperative treatment of small residual disease. Depending on the location of the lesion, in some cases, brachytherapy is a treatment of choice. Clinical indications, different techniques, results, and complications are discussed in this work.