Muscle Strength and Power in People With Parkinson Disease: A Systematic Review and Meta-analysis.
No studies have synthesized the literature regarding mechanical muscle function (ie, strength, power, rate of force development [RFD]) in people with Parkinson disease (PD). Here, we aimed to expand our understanding of mechanical muscle function in people with PD (PwPD) by systematically reviewing (1) the psychometric properties of isokinetic/isometric dynamometry in PD, (2) the literature comparing mechanical muscle function in PwPD with healthy controls (HC), and (3) reported associations between muscle mechanical muscle function and functional capacity and/or disease severity. Systematic literature search in 6 databases. Included studies had to (1) enroll and report data on PwPD, (2) include assessment(s) of psychometric properties (ie, validity, reliability, responsiveness) of isokinetic/isometric dynamometry in PD, and/or (3) assess mechanical muscle function in both PwPD and HC using isokinetic/isometric dynamometry. A total of 40 studies were included. Aim 1 studies (n = 2) showed high reliability for isometric dynamometry (hip-abductor/dorsiflexor/trunk flexor-extensor/handgrip: intraclass correlations coefficients range = 0.92-0.98). Aim 2 studies (n = 40) showed impaired mechanical muscle function (ie, strength, power, RFD) in PwPD compared with HC (effect sizes range = 0.52-1.89). Aim 3 studies (n = 11) showed weak-to-strong associations between overall and lower extremities muscle strength and functional capacity and/or disease severity outcomes (ie, Unified Parkinson Disease Rating Scale). Sparse methodological evidence suggests high reliability when using dynamometry in PwPD. Muscle strength, power, and RFD are impaired in PwPD compared with HC. Muscle strength is associated with functional capacity and disease severity.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A403 ).


Production of lactic acid and fructose from media with cane sugar using mutant of Lactobacillus delbrueckii NCIM 2365.
To examine the potential of Lactobacillus delbrueckii mutant, Uc-3 to produce lactic acid and fructose from sucrose-based media. The mutant of L. delbrueckii NCIM 2365 was cultivated in shake flask containing hydrolysed cane sugar (sucrose)-based medium. The lactic acid yield and volumetric productivity with hydrolysed cane concentration up to 200 g l(-1) were in the range of 92-97% of the theoretical value and between 2.7 and 3.8 g l(-1) h(-1), respectively. The fructose fraction of the syrup produced was more than 95% when the total initial sugar concentration in the medium was higher (150-200 g l(-1)). There are no unwanted byproducts detected in the fermentation broth. We demonstrated that L. delbrueckii mutant Uc-3 was able to utilize glucose preferentially to produce lactic acid and fructose from hydrolysed cane sugar in batch fermentation process. These findings will be useful in the production of lactic acid and high fructose syrups using media with high concentrations of sucrose-based raw materials. This approach can lead to modification of the traditional fermentation processes to obtain value-added byproducts, attaining better process economics.


One-pot synthesis of graphene- cobalt hydroxide composite nanosheets (Co/G NSs) for electrocatalytic water oxidation.
We report a one-pot method for the preparation of graphene-cobalt hydroxide nanosheets (Co/G NSs) and their use as an effective elelctrocatalyst for water oxidation. Mechanical exfoliation of graphite via sonication produced graphene sheets, which were stabilized by the surface adsorption of a cationic surfactant (CTAB). In a subsequent step, varying amount of a cobalt complex [sodium hexanitrocobaltate(III)] was added which selectively bound with the positively charged head of surfactant. In the last step, cobalt complex was reduced with sodium borohydride to obtain Co/G NSs catalyst. The catalyst showed lower overpotential (280 mV) as compared to benchmark catalysts and decent stability and turnover frequency (TOF: 0.089 s-1) for oxygen evolution reaction (OER).


Determination of Low Loss in Isotopically Pure Single Crystal 28Si at Low Temperatures and Single Microwave Photon Energy.
The low dielectric losses of an isotopically pure single crystal 28Si sample were determined at a temperature of 20 mK and at powers equivalent to that of a single photon. Whispering Gallery Mode (WGM) analysis revealed large Quality Factors of order 2 × 106 (dielectric loss ~5 × 10-7) at high powers, degrading to 7 × 105 (dielectric loss ~1.4 × 10-6 at single photon energy. A very low-loss narrow line width paramagnetic spin flip transition was detected with extreme sensitivity in 28Si, with very small concentration below 1010 cm-3 (less than 10 parts per trillion) and g-factor of 1.995 ± 0.008. Such determination was only possible due to the low dielectric photonic losses combined with the long lifetime of the spin transition (low magnetic loss), which enhances the magnetic AC susceptibility. Such low photonic loss at single photon energy combined with the narrow line width of the spin ensemble, indicate that single crystal 28Si could be an important crystal for future cavity QED experiments.


The influence of the total body exhaust suit on air and wound contamination in elective hip-operations.
An evaluation of the effect of total body exhaust clothing on air and wound contamination was made in an operating theatre with a zonal ventilation system. Sixty-four patients who underwent total hip replacement using the Charnley-Müller prosthesis were studied. The members of the surgical team wore total body exhaust suits (TBE-suit), or conventional theatre clothing (C-clothing) at alternate operations. Nearly half of the patients in each group were given prophylactic antibiotics. Both the mean and median values of airborne bacteria in the operating theatre were significantly lower during operations with TBE-suits than with conventional theatre clothing. The lowest number, 4.0 cfu/m3, was found at the site of the operation wound. Cultures from adhesive drapes showed growth in 46 per cent of the C-group and in 43 per cent of the TBE-group samples. Wound washouts showed growth in 43 per cent of the C-group and in 10 per cent of the TBE-group samples. Staphylococcus epidermidis was the most frequently isolated bacteria both from adhesive drapes and from wound washouts. The rate of superficial infections was slightly higher when C-clothing was used. Deep infections were found in one patient in the TBE-group and in two patients in the C-group. None of the infected patients had received prophylactic antibiotics.


Zigui-Yichong-Fang protects against cyclophosphamide-induced premature ovarian insufficiency via the SIRT1/Foxo3a pathway.
Zigui-Yichong-Fang (ZGYCF) is a traditional Chinese medicine prescription for the treatment of infertility and premature ovarian insufficiency (POI). It is clinically used to regulate hormone levels, improve ovarian reserve and increase pregnancy rate. However, the exact mechanism of action is not yet clear. This study aimed to explore the potential impact and mechanism of ZGYCF on POI, and provide a scientific basis for its clinical application. UHPLC‒MS/MS was used to identify the main compounds of ZGYCF. Female 8-week-old C57BL/6N mice were randomized into four group containing the vehicle control (Veh) group, the cyclophosphamide (CTX) model group, the low-dose ZGYCF (CTX-ZG-L) group and the high-dose ZGYCF (CTX-ZG-H) group. A mouse POI model was induced with a single intraperitoneal injection of CTX, and the therapeutic effects of different doses of ZGYCF on POI were evaluated according to the ovarian weight coefficient, serum AMH, serum E2, ovarian histomorphology and follicle counts. After the dose screening experiment, the CTX-ZG-L group was renamed the CTX-ZG group and subjected to follow-up experiments. RNA-seq was used to explore the mechanism of POI and the therapeutic mechanism of ZGYCF on POI in Veh group, CTX group and CTX-ZG group. The mechanism of action of ZGYCF on POI were determined by measuring serum hormone level, histomorphology, follicle counts, protein expression and acetylation modification in groups of Veh, CTX, CTX-ZG and CTX-ZG-Nam (SIRT1 inhibitor). A total of 37 compounds in ZGYCF were identified. ZGYCF attenuated the morphological changes in ovarian tissue in POI model mice, increased serum AMH and E2 levels, reduced the damage to primordial follicles and other follicles at all stages, and protected ovarian reserve. RNA-seq results suggested that the genes expression of the PI3K signaling and apoptosis signaling pathways was increased in POI mice, while ZGYCF upregulated SIRT1 gene and the expression of estradiol, apoptosis inhibition and other signaling pathway genes. Immunohistochemical staining, TUNEL staining, Western blot analysis and immunoprecipitation results showed that in CTX group, SIRT1 expression and Foxo3a nuclei localization were decreased, while Ac-Foxo3a, p-AKT, p-Foxo3a and apoptotic markers were upregulated. After administration of ZGYCF, these conditions were reversed, however, after treatment with the SIRT1 inhibitor, the results were opposite to those of ZGYCF. Acetylated Foxo3a plays an important role in the occurrence of POI. ZGYCF improves the ovarian reserve of CTX-induced POI mice by activating SIRT1-mediated deacetylation of Foxo3a, and played a role in the treatment of POI. SIRT1 may be a novel target for ZGYCF to ameliorate POI.


Post-thyroid FNA testing and treatment options: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference.
The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational Web site and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document addresses follow-up procedures and therapeutic options for suggested diagnostic categories. Follow-up options for "nondiagnostic" and "benign" thyroid aspirates are given. The value of ultrasound examination in the follow-up of "nondiagnostic" and "benign" thyroid aspirates is discussed. Ultrasound findings requiring reaspiration or surgical resection are described as are the timing and length of clinical and ultrasonographic surveillance for cytologically "benign" nodules. Options for surgical intervention are given for the diagnostic categories of "atypical/borderline," "follicular neoplasm," "suspicious for malignancy" and "malignant" (http://thyroidfna.cancer.gov/pages/info/agenda/).


The role of surgery in the treatment of colorectal metastases from primary skin melanoma.
The study assessed the role of colorectal surgery in the treatment of metastatic melanoma and identified patients who can most benefit from surgical resection. A retrospective analysis was made of 34 consecutive patients with skin melanoma who underwent surgical resection of large bowel metastasis. The median disease-free interval between diagnosis of the primary and metastatic melanoma was 24 (7-98) months. Nine (27%) patients underwent emergency surgery for obstruction and 25 (73%) had an elective procedure. Resection with curative intent was performed in 14 (41%) and palliative resection in 20 (59%) patients. There was no postoperative mortality and morbidity occurred in 9%. The median survival following surgery was 11.5 (4-68) months. The 1-, 2- and 5-year survival rates were 50%, 32% and 17% respectively. Median survival was significantly increased in patients without extra-abdominal metastases, with no evidence of non-large-bowel metastases, if the disease-free interval was longer than 24 months and when curative resection was performed. In multivariate analysis, an apparently complete or palliative resection and the absence or presence of extra-abdominal metastases were the most important prognostic factors. An aggressive surgical approach to large bowel metastatic melanoma results in good palliation and effective relief of symptoms with acceptable morbidity and mortality.


N-[3-(4-Fluoro-benz-yl)-2,4-dioxo-1,3-diaza-spiro-[4.5]dec-8-yl]-2-methyl-benzene-sulfonamide.
In the title compound, C(22)H(24)FN(3)O(4)S, the cyclo-hexane ring adopts a chair conformation and the five-membered ring is essentially planar, with a maximum deviation of 0.040 (2) Å. The dihedral angles between the five-membered ring and the tolyl and fluoro-benzene rings are 56.74 (12) and 89.88 (12)°, respectively. The two terminal benzene rings make a dihedral angle of 63.53 (12)°. The crystal structure displays inter-molecular C-H⋯O and N-H⋯O hydrogen bonds. An intra-molecular C-H⋯O hydrogen bond also occurs.


Positive selection of primate genes that promote HIV-1 replication.
Evolutionary analyses have revealed that most host-encoded restriction factors against HIV have experienced virus-driven selection during primate evolution. However, HIV also depends on the function of many human proteins, called host factors, for its replication. It is not clear whether virus-driven selection shapes the evolution of host factor genes to the extent that it is known to shape restriction factor genes. We show that five out of 40 HIV host factor genes (13%) analyzed do bear strong signatures of positive selection. Some of these genes (CD4, NUP153, RANBP2/NUP358) have been characterized with respect to the HIV lifecycle, while others (ANKRD30A/NY-BR-1 and MAP4) remain relatively uncharacterized. One of these, ANKRD30A, shows the most rapid evolution within this set of genes and is induced by interferon stimulation. We discuss how evolutionary analysis can aid the study of host factors for viral replication, just as it has the study of host immunity systems.


Reaching target lipid levels in patients at high risk of cardiovascular event: the experience of a Canadian tertiary care lipid clinic.
To determine the proportion of high risk patients followed at a tertiary care lipid clinic who met recommended lipid targets and to identify predictors of reaching goal lipid levels. A retrospective cohort study of 502 high risk patients followed between 1983 and 2003. Clinical and demographic data and fasting lipid profiles were extracted from each patient's first two clinic visits as well as the most recent visit. All patients in this study were at high risk of cardiovascular events due to dyslipidemia. At "Visit 1", only 55 (11.0%) of patients were at target TC/HDL-C < 4.0, and 97 (19.3%) of patients met target LDL-C < 2.5 mmol/l. At "Visit 3", 229 (45.8%) patients reached TC/HDL-C target, and 216 (43.2%) patients were at LDL-C target. The mean change in lipid values between Visit 1 and Visit 3 was significant (p = 0.0002) for LDL-C and (p < 0.0001) for TC/HDL-C. The use of statins, niacin, or salmon oil were all significantly associated with reaching TC/HDL-C target and LDL-C target, as well male gender, diabetes mellitus and peripheral vascular disease were also associated with reaching LDL-C target. Increasing age and lower body mass index were associated with reaching goal TC/HDL-C. The mean absolute changes in lipid values were significant and median lipid levels approached target levels in patients followed at specialized clinic, however the majority of high risk patients are not meeting goal lipid levels.


Allopurinol and kidney function: An update.
Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.


Antibacterial PLA/Mg composite with enhanced mechanical and biological performance for biodegradable orthopedic implants.
Biodegradability, bone-healing rate, and prevention of bacterial infection are critical factors for orthopedic implants. Polylactic acid (PLA) is a good candidate biodegradable material; however, it has insufficient mechanical strength and bioactivity for orthopedic implants. Magnesium (Mg), has good bioactivity, biodegradability, and sufficient mechanical properties, similar to that of bone. Moreover, Mg has an inherent antibacterial property via a photothermal effect, which generates localized heat, thus preventing bacterial infection. Therefore, Mg is a good candidate material for PLA composites, to improve their mechanical and biological performance and add an antibacterial property. Herein, we fabricated an antibacterial PLA/Mg composite for enhanced mechanical and biological performance with an antibacterial property for application as biodegradable orthopedic implants. The composite was fabricated with 15 and 30 vol% of Mg homogeneously dispersed in PLA without the generation of a defect using a high-shear mixer. The composites exhibited an enhanced compressive strength of 107.3 and 93.2 MPa, and stiffness of 2.3 and 2.5 GPa, respectively, compared with those of pure PLA which were 68.8 MPa and 1.6 GPa, respectively. Moreover, the PLA/Mg composite at 15 vol% Mg exhibited significant improvement of biological performance in terms of enhanced initial cell attachment and cell proliferation, whereas the composite at 30 vol% Mg showed deteriorated cell proliferation and differentiation because of the rapid degradation of the Mg particles. In turn, the PLA/Mg composites exerted an antibacterial effect based on the inherent antibacterial property of Mg as well as the photothermal effect induced by near-infrared (NIR) treatment, which can minimize infection after implantation surgery. Therefore, antibacterial PLA/Mg composites with enhanced mechanical and biological performance may be a candidate material with great potential for biodegradable orthopedic implants.


A versatile strategy for high-resolution separation of reducing glycan mixtures as hydrazones by two-dimensional high-performance liquid chromatography.
Glycomics analysis has been undermined by the lack of structurally defined individual glycans as model compounds. However, it is challenging to prepare individual glycans from natural resources, mainly due to separation difficulties caused by highly diverse structure, complicated mixture form and chromophore-free property of naturally-existing glycans. In this study, we report a simple, universal and low-cost glycan separation strategy, glycoselection, which allows preparation of individual reducing glycans from their mixtures through reversible chromogenic derivatization by hydrazide chemistry in combination with two-dimensional high-performance liquid chromatography (2D-HPLC). Investigations on reaction conditions using lactose and maltodextrin as model glycans showed the feasibility of reversible hydrazide labeling and one-pot hydrazone conversion under mild conditions, the good stability of hydrazone-form derivatives of glycans in solution and the difference among seven selected hydrazine-carrying chromogenic reagents in product yields during glycan labeling and post-column detagging. The 2D-HPLC separation conditions were established on maltodextrin, from which fourteen highly-purified individual reducing oligo-glucans were ultimately obtained. Using this strategy, we also successfully prepared and identified eleven individual neutral reducing N-glycans from chicken ovalbumin and thirteen individual neutral reducing oligosaccharides and eight individual sialylated ones from human milk, demonstrating its good applicability to different types of reducing glycans as well as biological samples. Given the compatibility of individual reducing glycans with almost all of glycan derivatization protocols and analytical techniques of glycans and the potential of the method for larger scale application, this work provides a universal approach to compound-specific analysis of natural glycans and has great significance for glycomics studies.


Disturbed eating attitudes, coping styles, and subjective quality of life in adolescents with Type 1 diabetes.
To evaluate coping styles and quality of life in youth with Type 1 diabetes with and without eating disorders and to identify relationships between these variables in each group. Adolescents were evaluated for eating disorders with a two-stage diagnostic procedure. Adolescents with and without eating disorders then provided data on coping styles and on subjective well-being. Adolescents with Type 1 diabetes and disordered eating behavior reported more often blaming themselves and resorting to wishful thinking and poorer physical and psychosocial quality of life than do adolescents with Type 1 diabetes without disordered eating behavior. Specific coping strategies were also positively linked with quality of life and metabolic control. Eating disorders and disordered eating behavior in adolescents with Type 1 diabetes seem to be associated with certain negative and avoidant coping strategies and with impeded physical and bio-psychosocial well-being.


Unstable hemoglobin Montreal II uncovered in an adult with unexplained hemolysis exacerbated by a presumed viral infection: a case report.
Unstable hemoglobinopathies are rare inherited disorders of hemoglobin causing a reduction of hemoglobin molecule solubility. This results in an unstable hemoglobin tetramer/globin polypeptide, which precipitates within the red blood cell. Affected red blood cells have a reduced lifespan due to oxidative stress and cellular rigidity, and tend to be phagocytized by spleen macrophages more rapidly. Unstable hemoglobin is frequently under- or misdiagnosed, because its clinical presentation varies broadly. Therefore, testing for unstable hemoglobinopathies is indicated in cases of unexplained hemolytic anemia. However, this approach is not systematically followed in clinical practice. A 25-year-old Caucasian man with a recent history of a presumed viral upper respiratory infection was referred to the hematology outpatient clinic because of hemolytic anemia. The patient had scleral icterus, moderate splenomegaly, and mild macrocytic anemia with high reticulocyte count. Unconjugated bilirubin and lactate dehydrogenase were elevated. Haptoglobin was undetectable. Direct antiglobulin test was negative. Blood smear examination revealed anisopoikilocytosis, polychromasia, bite cells, and basophilic stippling, but no Heinz bodies. High-performance liquid chromatography and capillary electrophoresis showed slightly increased hemoglobin A2, normal fetal hemoglobin, and a variant hemoglobin. Deoxyribonucleic Acid sequencing revealed the heterozygous mutation c430delC in the beta-globin gene hallmark of hemoglobin Montreal II and the heterozygous mutation c287C>T in the alpha-globin gene corresponding to hemoglobin G-Georgia, indicative of the not yet described combination of double-heterozygous hemoglobin Montreal II and hemoglobin G-Georgia variants. Hemoglobinopathy Montreal II was here not associated with β-thalassemia syndrome, and carriers did not show ineffective erythropoiesis. In addition to the case report, we provide information about the largest pedigree with hemoglobinopathy Montreal II identified to date. We emphasize that a transitory acute condition may uncover an underlying inherited red blood cell disorder. In this regard, awareness should be raised among hematologists caring for adult patients that unstable hemoglobinopathies should be considered in the differential diagnosis of unexplained hemolytic anemias.


The combined effects of temperature and food consumption on body weight, egg production and developmental time in Chaoborus crystallinus De Geer (Diptera: Chaoboridae) : Some new evidence for the adaptive value of vertical migration.
Chaoborus crystallinus fourth-instar larvae were reared individually at 14°, 17° and 20° C under different food conditions. Daphnia magna of 1.25 mm average length served as prey. The following were measured: amount of prey ingested, larval weight gain, duration of fourth instar, body weight of the adults, and egg number per female. At a given temperature, the body weight, egg-number and developmental rate increased with food consumption. At a given food consumption, higher temperatures caused a decrease in body weight and egg number, and an increase in developmental rate. Gross production efficiencies for fourth-instar larvae were highest at temperatures around 17° C. The results clearly indicate that from an energetic point of view higher temperatures are disadvantageous. In C. crystallinus vertical migration is evidently a way of lowering the temperature to which the animals are exposed and hence optimizing food conversion into biomass and offspring production, especially if prey densities are below the saturation level.


Two-dimensional Doppler echocardiographic assessment of closure of the ductus arteriosus in normal newborn infants.
To elucidate the mechanism involved in closure of the ductus arteriosus (DA), 50 normal full-term infants were examined with two-dimensional and pulsed Doppler echocardiography. The examinations were performed initially within 1 hour after delivery and serially for 3 days. The two-dimensionally derived long-axis plane of the DA disclosed a characteristic localized protrusion into its lumen in 30% of the subjects within 1 hour, in 80% by 4 hours, in 96% by 8 hours, and in all by 24 hours after birth. In 10 infants in whom the intraluminal protrusion did not appear within 4 hours after birth, none had any recognizable changes in the inner diameter or length of the DA during this initial period. The development of the intraluminal protrusion resulted in localized narrowing of the ductal lumen. Doppler echocardiography revealed a high-velocity jet within and downstream from the narrowed portion of the DA. Thereafter, ductal narrowing progressed along the entire length. The intraluminal protrusion may be early evidence of ductal changes leading to eventual functional and anatomic closure.


Evaluation of Ketamine for Excited Delirium Syndrome in the Adult Emergency Department.
Excited delirium syndrome (ExDS) is characterized by delirium, agitation, and hyperadrenergic autonomic dysfunction. A guideline for ExDS management, which recommends the use of ketamine as a second-line agent, was implemented in our hospital's adult emergency department (ED). The primary objective was to determine whether ketamine, 1 mg/kg intravenous (i.v.) or 2 mg/kg intramuscular (i.m.), is being used according to the ExDS guideline. Secondary objectives included evaluating the specific agents, routes, and dosages used to manage ExDS and the safety and efficacy of ketamine. Single-center, retrospective chart review of patients who received ketamine for the management of ExDS in the ED. Efficacy was measured by documented Richmond Agitation Sedation Scale (RASS) scores. Safety was assessed through evaluation of vital signs and adverse effects. Thirty-one patients met inclusion criteria. Eight (25.8%) of them received ketamine for ExDS in adherence with all aspects of the guideline. Administration of ketamine led to a statistically significant decrease in median RASS score of 4 (interquartile range [IQR] 3 to 4) vs. 0 (IQR 2 to -1) (p = 0.001). There were no statistically significant differences in vital signs or RASS scores in our subgroup analyses of patients treated according to protocol and of those treated with ketamine, 2 mg/kg i.m. We found discordance between current practice and our department's ExDS guideline for patients managed with ketamine. Despite the lack of adherence to departmental guidelines and allowing for limitations of this analysis due to small sample size, the use of low-dose, 1 mg/kg i.v. or 2 mg/kg i.m., ketamine was effective and appears to be a reasonable option as second-line therapy for ExDS.


[Explaining discrepancies in self-reported quality of life in frail older people: a mixed-methods study].
Most research on (multidimensional) frailty focuses on deficits and risks of adverse outcomes. However, frail older people can still report positive outcomes, such as a relatively high QoL. In order to develop more positively oriented prevention strategies, this exploratory study aimed (a) to identify characteristics related to QoL among frail older people; and (b) to explain discrepancies between higher and lower levels of QoL, with a specific focus on strengths frail older people with a higher QoL still may have. Quantitative and qualitative data was gathered by means of semi-structured interviews with Flemish community-dwelling, frail older people with higher (n = 16) and lower QoL levels (n = 18). Quantitative analyses showed that frail older people with a higher QoL were older, had lower levels of psychological frailty, and reported higher meaning in life compared to those with a lower QoL. Outcomes of qualitative analysis showed that participants in the high QoL subgroup adapted more effectively to difficulties, had more things in prospect, performed more activities, and were more satisfied with their social network compared to the low QoL subgroup. To conclude, this exploratory study suggests possibilities to promote and improve QoL by strengthening specific resources among frail older people.Please note that an English version of this article has been published in BMC Geriatrics: van der Vorst A, Zijlstra GAR, De Witte N, Vogel RGM, Schols JMGA, Kempen GIJM, D‑SCOPE Consortium. Explaining discrepancies in self-reported quality of life in frail older people: a mixed-methods study. BMC Geriatr. 2017;17(1): 251. https://doi.org/10.1186/s12877-017-0641-y .


Damages of DNA in tritiated water.
Tritium is a radioisotope of hydrogen emitting low energy β-rays in disintegration to 3He. DNA molecules are damaged mainly by β-ray irradiation, and additional damages can be induced by break of chemical bond by nuclear transmutation to inert 3He. Deep knowledges of the mechanisms underlying DNA damages lead to better understanding of biological effects of tritium. This chapter reviews recent experimental and computer simulation activities on quantitative evaluation of damage rates by β-ray irradiation and nuclear transmutation. The rate of DNA double-strand breaks in tritiated water has been examined using a single molecule observation method. The effects of β-ray irradiation were not noticeable at the level of tritium concentration of ∼kBq/cm3, while the irradiation effects were clear at tritium concentrations of ∼MBq/cm3. The factors affecting on the DSB rate are discussed. A new image processing method for the automatic measurement of DNA length using OpenCV and deep learning is also introduced. The effects of tritium transmutation on hydrogen bonds acting between the two main strands of DNA have been examined using molecular dynamics simulations. The study showed that the collapsing of DNA structure by the transmutation can be quantitatively evaluated using the root mean square deviation of atomic positions.


Central Orexin A Affects Reproductive Axis by Modulation of Hypothalamic Kisspeptin/Neurokinin B/Dynorphin Secreting Neurons in the Male Wistar Rats.
It is an established fact that orexin plays an important role in regulating the reproductive axis and the secretions of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH). However, its precise cellular and molecular mechanisms are not fully recognized. Accordingly, the aim of the present study is to find out whether the central injection of orexin A (OXA) and its antagonists, SB-334867 (as orexin receptor antagonist 1; OX1RA) and JNJ-10397049 (as orexin receptor antagonist 2; OX2RA), either alone or in combination, can leave any impact on the reproductive axis (either hormonal or behavioral) in the male Wistar rats. Furthermore, in order to see whether OXA signals can be relayed through the pathway of kisspeptin/neurokinin B/dynorphin (known as KNDy neurons, a neural network which works upstream of GnRH neurons) or not, the relative gene expression of these neuropeptides were measured. Overall, the data from radioimmunoassay revealed that OXA significantly decreases the mean serum level of LH and testosterone and, in a similar vein, its antagonists neutralize this impact. Moreover, data from real-time quantitative PCR indicated that OXA has significantly reduced the hypothalamic expression of Gnrh. In this line, the gene expressions of Kisspeptin and Neurokinin b decreased. However, OXA antagonists neutralize this impact. Also, the expression of Dynorphin gene was upregulated by the following application of the OXA. The results of this study are related to the impact of orexin on the reproductive axis. It is recommended that KNDy neurons as the interneural pathway relay the information of orexin to the GnRH neurons.


A Gradient Boosting Machine Learning Model for Predicting Early Mortality in the Emergency Department Triage: Devising a Nine-Point Triage Score.
Emergency departments (ED) are becoming increasingly overwhelmed, increasing poor outcomes. Triage scores aim to optimize the waiting time and prioritize the resource usage. Artificial intelligence (AI) algorithms offer advantages for creating predictive clinical applications. Evaluate a state-of-the-art machine learning model for predicting mortality at the triage level and, by validating this automatic tool, improve the categorization of patients in the ED. An institutional review board (IRB) approval was granted for this retrospective study. Information of consecutive adult patients (ages 18-100) admitted at the emergency department (ED) of one hospital were retrieved (January 1, 2012-December 31, 2018). Features included the following: demographics, admission date, arrival mode, referral code, chief complaint, previous ED visits, previous hospitalizations, comorbidities, home medications, vital signs, and Emergency Severity Index (ESI). The following outcomes were evaluated: early mortality (up to 2 days post ED registration) and short-term mortality (2-30 days post ED registration). A gradient boosting model was trained on data from years 2012-2017 and examined on data from the final year (2018). The area under the curve (AUC) for mortality prediction was used as an outcome metric. Single-variable analysis was conducted to develop a nine-point triage score for early mortality. Overall, 799,522 ED visits were available for analysis. The early and short-term mortality rates were 0.6% and 2.5%, respectively. Models trained on the full set of features yielded an AUC of 0.962 for early mortality and 0.923 for short-term mortality. A model that utilized the nine features with the highest single-variable AUC scores (age, arrival mode, chief complaint, five primary vital signs, and ESI) yielded an AUC of 0.962 for early mortality. The gradient boosting model shows high predictive ability for screening patients at risk of early mortality utilizing data available at the time of triage in the ED.


Unusual dose--response of chromosome abberrations induced in human lymphocytes by very low dose exposures to tritium.
Leukocyte cultures of human peripheral blood were chronically exposed for 48 h to tritiated water and [3H]thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and [3H]thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose--response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extrapolation from the linear relation. Partial-hit or partial-target kinetic events appears at very low dose exposure.


Multidimensional growth measurements of abdominal aortic aneurysms.
Monitoring the expansion of abdominal aortic aneurysms (AAAs) is critical to avoid aneurysm rupture in surveillance programs, for instance. However, measuring the change of the maximum diameter over time can only provide limited information about AAA expansion. Specifically, regions of fast diameter growth may be missed, axial growth cannot be quantified, and shape changes of potential interest for decisions related to endovascular aneurysm repair cannot be captured. This study used multiple centerline-based diameter measurements between the renal arteries and the aortic bifurcation to quantify AAA growth in 51 patients from computed tomography angiography (CTA) data. Criteria for inclusion were at least 1 year of patient follow-up and the availability of at least two sufficiently high-resolution CTA scans that allowed an accurate three-dimensional reconstruction. Consequently, 124 CTA scans were systematically analyzed by using A4clinics diagnostic software (VASCOPS GmbH, Graz, Austria), and aneurysm growth was monitored at 100 cross-sections perpendicular to the centerline. Monitoring diameter development over the entire aneurysm revealed the sites of the fastest diameter growth, quantified the axial growth, and showed the evolution of the neck morphology over time. Monitoring the development of an aneurysm's maximum diameter or its volume over time can assess the mean diameter growth (r = 0.69, r = 0.77) but not the maximum diameter growth (r = 0.43, r = 0.34). The diameter growth measured at the site of maximum expansion was ~16%/y, almost four times larger than the mean diameter expansion of 4.4%/y. The sites at which the maximum diameter growth was recorded did not coincide with the position of the maximum baseline diameter (ρ = 0 .12; P = .31). The overall aneurysm sac length increased from 84 to 89 mm during the follow-up (P < .001), which relates to the median longitudinal growth of 3.5%/y. The neck length shortened, on average, by 6.2% per year and was accompanied by a slight increase in neck angulation. Neither maximum diameter nor volume measurements over time are able to measure the fastest diameter growth of the aneurysm sac. Consequently, expansion-related wall weakening might be inappropriately reflected by this type of surveillance data. In contrast, localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements over the entire aneurysm sac. This information might further reinforce the quality of aneurysm surveillance programs.


Effect of ovine prolactin on serum somatomedin bioactivity in hypophysectomized female rats.
Ovine prolactin (oPRL) increased serum somatomedin (SM) bioactivity in hypophysectomized female rats. ACTH, in small but not large doses, augmented this oPRL effect. These results suggest that in the female rat PRL may regulate SM production. Adrenal factors may variably modulate SM production or serum SM bioactivity.


Age-induced accumulation of methylmalonic acid promotes tumour progression.
The risk of cancer and associated mortality increases substantially in humans from the age of 65 years onwards1-6. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy2,3,7,8. For decades, this link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the established role of diet, exercise and small molecules that target the pace of metabolic ageing9-12. Here we show that metabolic alterations that occur with age can produce a systemic environment that favours the progression and aggressiveness of tumours. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is upregulated in the serum of older people and functions as a mediator of tumour progression. We traced this to the ability of MMA to induce SOX4 expression and consequently to elicit transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, the accumulation of MMA represents a link between ageing and cancer progression, suggesting that MMA is a promising therapeutic target for advanced carcinomas.


REIN: a tool at the service of health authorities
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of its link with health authorities, the following key messages were retained. One of the purposes of REIN is to contribute to a better understanding about patient management and its evolution, and thus to be called upon to develop health strategies aimed at improving the prevention and treatment of chronic renal failure. Indeed, the planning of the supply and the evaluation of the treatment are important issues for the public health decision-makers who must have the relevant indicators and tools to help them in their decision-making and follow-up processes. REIN is clearly identified as a source of information by institutional partners, as is shown by the various requests made by the Regional health agencies (ARS), the French National Authority for Health (HAS) and the General Directorate for Healthcare Services (DGOS), as well as other health authorities. It allows estimating the needs of the population within the framework of decree nos. 2002-1197 and 2002-1198 of September 2002 relating to the treatment of chronic renal failure by renal dialysis. The recent possibility of probabilistic matching of REIN data with the data from the National Healthcare Data System (SNDS) for a pseudonymised individual allows for more detailed studies on the different care pathways, as well as evaluating the impact of the different actions or experiments that are set up, with the help of detailed clinical information from the REIN and, among other things, the expenses reimbursed by the Health Insurance.


Synthesis of 2,3,4a,11b-tetrahydro-oxazino[2,3-c]benzopyran-9-carbonitriles as ATP-sensitive potassium channel openers.
A series of optically active tetrahydro-oxazino[2,3-c]benzopyran derivatives have been synthesized and evaluated for potassium channel opening activity. (4aR,11bR)-1-Benzoyl- 5,5-dimethyl-2,3,4a,11b-tetrahydro-oxazino[2,3-c]benzopyran-9-carb onitrile ((-)-11e) was identified as a bladder-selective potassium channel opener (IC50, bladder = 8.15 microM, IC50, portal vein = 34.5 microM).


Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems.
Within-host infection dynamics of a recent field isolate of foot-and-mouth disease virus (FMDV), serotype O, topotype South East Asia, lineage Myamar'98 were evaluated in sheep using four different systems for virus exposure. Two novel, simulated natural, inoculation systems consisting of intra-nasopharyngeal (INP) deposition and aerosol inoculation were evaluated in comparison with two conventional systems: coronary band inoculation and direct contact exposure. All four exposure systems were efficient in generating consistently severe, generalized FMD with synchronous clinical characteristics within exposure groups, indicating that this Myanmar98 strain is highly virulent in sheep. Clinical and virological dynamics were similarly rapid following INP- and coronary band inoculation, with both systems leading to significantly earlier detection of virus shedding when compared to aerosol inoculation and contact exposure. The data presented herein support application of the two optimized simulated natural inoculation systems as valid alternatives to conventionally used exposure systems for studies of FMDV pathogenesis and vaccinology in sheep. Furthermore, the data suggest that targeted exposure of the ovine pharynx is highly efficient for generating consistent FMDV infection, which supports critical involvement of this anatomic region as a site of primary virus replication in sheep.


Long-term efficacy of nusinersen and its evaluation in adolescent and adult patients with spinal muscular atrophy types 1 and 2.
The efficacy of nusinersen and its evaluation in patients with spinal muscular atrophy (SMA) has been established in clinical trials only for pediatric patients, not for adolescent and adult patients who developed SMA in infancy or early childhood. We report a long-term follow-up in adolescent and adult patients with SMA types 1 and 2. Nusinersen-treated patients with SMA types 1 and 2 between 2017 and 2022 were retrospectively reviewed. We compared baseline motor function tests with those after the final treatment. Physical and occupational therapists performed Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale-Expanded (HFMSE), and Revised Upper Limb Module (RULM). The Landau and Galant reflexes were not performed in CHOP-INTEND. Meaningful improvement was defined as CHOP-INTEND, 4; HFSME, 3; and RULM, 2. Seven patients with SMA (type 1, 1; type 2, 6) with a median age of 23 (range, 12-40)years were treated with nusinersen for 3.55 (1.78-4.53)years. Improvement was detected in CHOP-INTEND (pre, 5 [0-31]; post, 21 [0-39]; difference, 5 [0-26]; p = 0.100) without significance, although not in HFMSE (pre, 0 [0-3]; post, 0 [0-5]; difference, 0 [0-2]; p = 0.346) and RULM (pre, 1 [0-20]; post, 3 [0-21]; difference, 1 [0-2]; p = 0.089). Owing to prolonged treatment intervals with the COVID-19 pandemic, RULM worsened in two patients. Nusinersen was effective in long-term follow-up. Only CHOP-INTEND showed meaningful improvement. The interval between doses of nusinersen should not be prolonged even with the COVID-19 pandemic.


Fibonacci Sequence and Supramolecular Structure of DNA.
We proposed a new model of supramolecular DNA structure. Similar to the previously developed by us model of primary DNA structure [11-15], 3D structure of DNA molecule is assembled in accordance to a mathematic rule known as Fibonacci sequence. Unlike primary DNA structure, supramolecular 3D structure is assembled from complex moieties including a regular tetrahedron and a regular octahedron consisting of monomers, elements of the primary DNA structure. The moieties of the supramolecular DNA structure forming fragments of regular spatial lattice are bound via linker (joint) sequences of the DNA chain. The lattice perceives and transmits information signals over a considerable distance without acoustic aberrations. Linker sequences expand conformational space between lattice segments allowing their sliding relative to each other under the action of external forces. In this case, sliding is provided by stretching of the stacked linker sequences.


High-mobility group box 1 protein activates hepatic stellate cells in vitro.
Our previous study noticed remarkably elevated titers of anti-high-mobility group box 1 (HMGB1) antibodies in sera during the tolerance induction phase of a rat tolerogenic orthotopic liver transplantation (OLT) as well as in sera of clinically drug-free patients. We hypothesized that the release of nonhistone nuclear protein HMGB1 during rejection may play a pathogenic role in deteriorating post-OLT graft functions, such as inducing liver fibrosis. This study sought to investigate whether HMGB1 can directly activate hepatic stellate cells (HSCs) and drive them toward fibrogenesis. The cultured HSCs were treated with recombinant HMGB1. RT-PCR and Western blotting analysis were used to measure alpha-smooth muscle actin (alpha-SMA) expression. Conditioned media were collected for gelatin zymography to monitor the activities of collagen-degrading matrix metalloproteinases (MMPs). HMGB1 at concentrations > 1 ng/mL significantly stimulated HSC growth as revealed by proliferation and BrdU assays. alpha-SMA gene and protein expression were significantly up-regulated by HMGB1, whereas the MMP-2, but not MMP-9, activity was suppressed by HMGB1 treatment. Our data suggested that HMGB1 protein, once released during the rejection phase of OLT, activated HSCs and exhibited profibrogenic effects on liver grafts either by increasing the HSC population and extracellular matrix content in liver grafts, or by transforming HSCs into myofibroblasts. Neutralization with anti-HMGB1 antibody was suggested to be a therapeutic modality applicable to prevent fibrogenesis in post-OLT liver grafts.


Central origin of the hypoxic depression of breathing in the newborn.
These studies were designed to ascertain whether the mechanism underlying the depressive component of the response to hypoxia in the newborn is similar to that in the fetus. We studied the response to hypoxia in 5-10 day old unanaesthetized rabbit pups before and after decerebration at or near the level of the midbrain/pontine junction. In the intact animal, hypoxia caused an initial stimulation of minute volume (VE) followed by a depression which was due to a decrease in both tidal volume (VT) and respiratory frequency (f). Decerebration abolished the depressive component of the response; the initial increase in VE on exposure to 7% O2 was now maintained, mainly due to a sustained increase in VT. We conclude that there is a central mechanism sited in or above the upper pons which is involved in the depressive component of the biphasic response to hypoxia. It is likely that this mechanism is similar to that mediating the hypoxic depression of breathing in the fetus.


Radial arterial access is a safe alternative to brachial artery and femoral artery access for endovascular lower extremity peripheral arterial disease.
Radial artery access is a well-described technique that has proven to be safe and efficacious in percutaneous cardiac intervention. This technique has been used with increased frequency in the treatment of lower extremity peripheral arterial disease (LE-PAD); however, the overall safety has not yet been well described in the vascular surgery literature. We sought to evaluate the safety of this technique compared with retrograde femoral artery access and brachial artery access (BA) in the treatment of PAD. The Vascular Quality Initiative database was used to identify all patients who underwent single site percutaneous access (retrograde femoral access [FA], BA, radial access [RA]) for treatment of LE-PAD from September 2016 through September 2019. Patients who underwent multiple access sites for intervention were excluded. Primary outcome was significant access site complications (ASCs), defined as those requiring treatment (blood transfusion, interventional treatment, or surgical treatment). Minor ASCs were also reported. The cohort comprised 61,203 patients (270 RA, 1210 BA, and 59,723 FA) with an average age of 68 years and who were 59.6% male. The RA and BA groups had higher rates of prior endarterectomy or bypass compared with the FA group (66.7% RA; 86.0% BA; 50.2% FA; P < .001). RA was more often used for single-segment treatments (82% vs 74% [P < .020] and more aortoiliac arterial segments (59.6% vs 21.0% [P < .001]). ASC occurred in 1329 patients (2.7%), including minor ASC (996 [1.6%]) and significant ASC (333 [0.54%]). Significant ASC were less common after FA and RA compared with BA (RA, 1 [0.37%]; FA, 307 [0.51%]; BA, 25 [2.1%]; P < .001). On multivariate analysis, BA was the strongest predictor of significant ASC (odds ratio, 2.75; 95% confidence interval, 1.73-4.36; P < .001). Significant ASC was no different after RA compared with FA (odds ratio, 0.60; 95% confidence interval, 0.08-4.33; P = .616). Other factors independently associated with significant ASC were sex, age, diabetes, chronic obstructive pulmonary disease, dialysis, and closure device use. RA as the primary access vessel for endovascular treatment of LE-PAD is safe when compared with other traditional access sites. When FA is not possible or desirable, the radial approach may provide suitable access to treatment with a better safety profile than BA.


Impact assessment of vehicle electrification pathways on emissions of CO2 and air pollution in Xi'an, China.
To assess the environmental impact of promoting the use of electric vehicles in road traffic on emissions of CO2 and air pollution in Xi'an, China, both the proportion of electric vehicles and the power generation mix should be considered. Here, vehicle ownership in 2021 served as the baseline scenario, and the vehicle development trend through 2035 was projected. Using emission factor models for fuel vehicles and the electricity generation required for running electric vehicles, this study estimated the related pollutants' emission inventories at 81 corresponding scenarios, in which differing vehicle electrification paths were coupled with power generation mix. Further, the degree to which different vehicle electrification paths impacted the CO2 and air pollutant emissions was also evaluated. The results show that, to achieve the goal of peak carbon emission in the road transport sector in Xi'an by 2030, the penetration rate of electric vehicles must reach at least 40 % in 2035, and the thermal power generation rate should satisfy the necessary coupling conditions. Although reducing the thermal power generation rate could mitigate the environmental problems, we find that electric vehicle development in Xi'an during 2021-2035 would still exacerbate SO2 emissions despite reducing the thermal power generation rate to 10 %. Finally, to avoid exacerbating the adverse effects on public health from vehicle-related pollutants, the penetration rate of electric vehicles should be at least 40 % in 2035, at which time for the 40 %, 50 %, 60 %, and 70 % scenarios, the corresponding thermal power generation rate should not exceed 10 %, 30 %, 50 %, and 60 %. This study systematically analyzed plausible development paths of electric vehicles from the perspectives of peak carbon emissions, air pollution control, and human health, whose findings can serve as a timely and valuable reference for reducing pollution and carbon in the field of road transport.


Considerations for determining optimal mouse caging density.
At the 2006 National Meeting of the American Association of Laboratory Animal Science, a panel discussed the question of what constitutes optimal or acceptable housing density for mice. Though there is a consensus that present guidelines are somewhat arbitrarily defined, scientific research has not yet been able to provide clear recommendations for amending them. Speakers explored the many factors that influence decisions on mouse housing, including regulatory requirements, scientific data and their interpretation, financial considerations and ethical concerns. The panel largely agreed that animal well-being should be the measure of interest in evaluating housing density and that well-being includes not only physical health, but also animals' behavior, productivity and preference.


Burden in caregivers of primary care patients with dementia: influence of neuropsychiatric symptoms according to disease stage (NeDEM project).
Caregiver burden is related to personal factors and patient characteristics and is greater when neuropsychiatric symptoms (NPSs) are present. Estimate the prevalence of burden among caregivers of dementia patients and its association with NPSs and identify NPSs causing greater caregiver distress according to dementia stage. A cross-sectional observational study in caregivers of noninstitutionalized dementia patients was conducted. Caregiver variables were sociodemographic, time of care, NPS-associated distress based on the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and burden based on the Zarit Burden Interview (ZBI). Patient variables were time since disease onset, Global Deterioration Scale (GDS) disease stage, functional assessment and NPS presence and intensity according to the Neuropsychiatric Inventory (NPI). The mean ZBI score, prevalence of burden and NPI-D score with 95% CIs at each dementia stage were estimated. Factors associated with burden were identified by multivariate analysis. Of the 125 caregivers included, 77.6% were women, with a mean age of 60.7 (± 14.3) years; 78.4% (95%CI: 71.0; 86.0) experienced burden. The mean ZBI score was 12.3 (95%CI: 11.6; 12.9) and increased according to NPS number (p = 0.042). The NPSs causing the most burden were disinhibition (93.5%), irritability (87.3%) and agitation (86.1%). Agitation, apathy, and sleep disorders were the NPSs generating the greatest overall caregiver distress; depression (max NPI-D 1.9), hyperactivity (max NPI-D 2.1), and psychosis symptoms (max NPI-D 1.6) generated the greatest distress at stage GDS 3, stages GDS 4-5, and stages GDS 6-7, respectively. The NPI score (OR = 1.0, 95%CI 1.0; 1.1), intensity of irritability (OR = 1.2, 95%CI 1.0; 1.6), disinhibition (OR = 2.6, 95%CI 1.1; 5.8) and hyperactivity subsyndrome (OR = 1.1, 95%CI 1.0; 1.2) were associated with caregiver burden. Other associated factors were female gender (OR = 6.0, 95%CI 1.6; 22.8), ≥ 8 h daily care (OR = 5.6, 95%CI 1.4; 22.8), working outside the home (OR = 7.6, 95%CI 1.8; 31.8), living with the patient (OR = 4.5, 95%CI 1.1; 19.6), kinship (OR = 5.4, 95%CI 1.0; 28.2) and lower patient education (OR = 8.3, 95%CI 2.3; 30.3). The burden on caregivers of dementia patients is high and associated with NPS presence and intensity. Disinhibition and irritability caused the highest burden. Depression, hyperactivity and psychosis produce more distress in mild, mild-moderate and severe dementia, respectively.


A case of Asperger's syndrome first diagnosed in adulthood.
A 25-year-old white male patient was admitted to the Department of Psychiatry, Division of Social Psychiatry, of the University of Vienna, Austria, for severe social withdrawal, selective mutism and outbursts of violence with attacks on his mother. Careful examination revealed the presence of all the typical symptoms of Asperger's syndrome. The diagnosis had never been made before, although the patient had a history of a difficult childhood with several admissions to a child psychiatric inpatient unit for 'obsessional neurosis' and an institutional career. It is stressed that, in view of the availability of treatments and the deleterious effect of the untreated condition in the sensitive years of personality development, early recognition and diagnosis of Asperger's syndrome are of utmost importance.


The relationship between the degree of dietary-induced hypercholesterolemia in the rabbit and atherosclerotic lesion formation.
A biochemical, histologic and morphometric evaluation of spontaneous, diet-induced (thoracic aorta) and injury-induced (iliac-femoral) atherosclerotic lesions was performed in rabbits maintained on varying levels of dietary cholesterol. Rabbits were meal-fed a 3% peanut oil, 3% coconut oil diet containing 0%, 0.1%, 0.25%, 0.5%, 1.0%, 1.5% or 2.0% cholesterol for 9 weeks. Plasma total cholesterol exposure (area under cholesterol-time curve (TC-AUC)) increased diet-dependently over the course of the study. VLDL and LDL cholesterol (VLDL-C, LDL-C) comprised 41% and 55%, respectively, of the plasma total cholesterol at cholesterol levels > 700 mg/dl (TC-AUC > 31,868 mg day/dl) and both VLDL-C and LDL-C were linearly related to TC-AUC (r = 0.98). Plasma TC-AUC was linearly related to thoracic aortic cholesteryl ester (CE) content (r = 0.74) and thoracic aortic lesion coverage (r = 0.66). In the injury-induced iliac-femoral lesion, plasma TC-AUC was linearly related to both iliac-femoral CE content (r = 0.80) and macrophage/lesion ratio (r = 0.64). At plasma cholesterol levels greater than 700 mg/dl, CE content of the iliac-femoral lesion ranged from 35 to 69 micrograms/mg dry defatted tissue, > 75% of the lesions were fibrofoamy in nature and macrophage/lesion area ratio was 0.46 to 0.55 while lesion area remained constant. VLDL-C and LDL-C were highly correlated with the CE content of both thoracic and iliac-femoral lesions, thoracic aortic lesion coverage and macrophage/lesion area ratio (r = 0.86-0.99). We conclude that the composition, extent and type of atherosclerotic lesion induced in rabbits is dependent upon the overall plasma cholesterol exposure, VLDL and LDL cholesterol content and whether lesions are induced by diet alone or both diet and chronic endothelial injury. In addition, various stages of atherosclerotic lesion formation can be replicated in the rabbit by titrating the animal's overall plasma cholesterol exposure.


Multicenter prospective randomized trial comparing standard esophagectomy with chemoradiotherapy for treatment of squamous esophageal cancer: early results from the Chinese University Research Group for Esophageal Cancer (CURE).
We conducted a prospective randomized trial to compare the efficacy and survival outcome by chemoradiation with that by esophagectomy as a curative treatment. From July 2000 to December 2004, 80 patients with potentially resectable squamous cell carcinoma of the mid or lower thoracic esophagus were randomized to esophagectomy or chemoradiotherapy. A two- or three-stage esophagectomy with two-field dissection was performed. Patients treated with chemoradiotherapy received continuous 5-fluorouracil infusion (200 mg/m2/day) from day 1 to 42 and cisplatin (60 mg/m2) on days 1 and 22. The tumor and regional lymphatics were concomitantly irradiated to a total of 50-60 Gy. Tumor response was assessed by endoscopy, endoscopic ultrasonography, and computed tomography scan. Salvage esophagectomy was performed for incomplete response or recurrence. Forty-four patients received standard esophagectomy, whereas 36 were treated with chemoradiotherapy. Median follow-up was 16.9 months. The operative mortality was 6.8%. The incidence of postoperative complications was 38.6%. No difference in the early cumulative survival was found between the two groups (RR = 0.89; 95% confidence interval, 0.37-2.17; log-rank test P = 0.45). There was no difference in the disease-free survival. Patients treated with surgery had a slightly higher proportion of recurrence in the mediastinum, whereas those treated with chemoradiation sustained a higher proportion of recurrence in the cervical or abdominal regions. Standard esophagectomy or chemoradiotherapy offered similar early clinical outcome and survival for patients with squamous cell carcinoma of the esophagus. The challenge lies in the detection of residue disease after chemoradiotherapy.


Comparison of fresh and frozen ejaculated spermatozoa in sibling oocyte recipient cycles.
Do IVF and intracytoplasmic sperm injection cycles using fresh and frozen ejaculated spermatozoa result in similar pregnancy outcomes in couples with non-male factor infertility? Retrospective cohort study; patients undergoing donor egg recipient cycles, in which oocytes from a single ovarian stimulation were split between two recipients, were reviewed. Two recipients of oocytes from a single donor were paired and categorized based on the type of ejaculated spermatozoa (fresh/frozen). Outcomes included delivery rate, implantation, pregnancy, pregnancy loss and fertilization rates. Of the 408 patients who received oocytes from a split donor oocyte cycle, 45 pairs of patients used discrepant types of ejaculated spermatozoa and were included in the study. Fertilization rate: fresh (74.8%); frozen (68.6%) (P = 0.13). Pregnancy rate: fresh (76%); frozen (67%); delivery rate: fresh (69%); frozen (44%); implantation rate was significantly higher: fresh (64%); frozen (36%) (P = 0.04). Rate of pregnancy loss was significantly higher in the frozen group compared with the fresh group (33% versus 5.9%, P = 0.013). Adjusted odds for delivery was 67% lower in the frozen group (95% CI 0.12, 0.89). Adjusted odds of pregnancy (adjusted OR 0.67, 95% CI 0.20, 2.27) and implantation (adjusted OR 0.5, 95% CI 0.12, 2.12) were not significantly different between the frozen and fresh sperm groups. In this model that controls for oocyte quality by using paired recipients from the same donor, frozen ejaculated spermatozoa resulted in lower delivery rates than those using fresh spermatozoa.


[Therapeutic options and prognosis of synchronous multiple primary colorectal carcinomas].
To investigate the therapeutic principles and prognosis of synchronous primary colorectal carcinomas (SCC). The data of 66 SCC patients surgically treated from 1984 to 2003 were retrospectively reviewed. The synchronous primary colorectal carcinomas were diagnosed and resected simultaneously in 65 patients except one that was misdiagnosed. Thirty patients underwent combined resection, 35 patients segmental resection. Sixty-two patients received radical resection, while three patients had palliative resection due to hepatic metastasis. The overall postoperative 3-, 5-, 10-year survival rates were 70.3%, 60.0%, 40.6%, respectively. In the patients who had simultaneous radical resection, the 3-, 5-, 10-year survival rates were 76.0%, 65.9%, 46.4% respectively. The extent of resection should be individually determined by the lesion location, extent and distance between the lesions, as well as the patient's general condition. More extensive bowel resection, such as total or subtotal colectomy are suggested for those patients with hereditary nonpolyposis colorectal carcinoma syndrome in order to reduce or avoid the risk of metachronous colorectal carcinoma. The postoperative survival in patients with synchronous primary colorectal carcinoma is similar to those with solitary lesion.


HIM-herbal ingredients in-vivo metabolism database.
Herbal medicine has long been viewed as a valuable asset for potential new drug discovery and herbal ingredients' metabolites, especially the in vivo metabolites were often found to gain better pharmacological, pharmacokinetic and even better safety profiles compared to their parent compounds. However, these herbal metabolite information is still scattered and waiting to be collected. HIM database manually collected so far the most comprehensive available in-vivo metabolism information for herbal active ingredients, as well as their corresponding bioactivity, organs and/or tissues distribution, toxicity, ADME and the clinical research profile. Currently HIM contains 361 ingredients and 1104 corresponding in-vivo metabolites from 673 reputable herbs. Tools of structural similarity, substructure search and Lipinski's Rule of Five are also provided. Various links were made to PubChem, PubMed, TCM-ID (Traditional Chinese Medicine Information database) and HIT (Herbal ingredients' targets databases). A curated database HIM is set up for the in vivo metabolites information of the active ingredients for Chinese herbs, together with their corresponding bioactivity, toxicity and ADME profile. HIM is freely accessible to academic researchers at http://www.bioinformatics.org.cn/.


The Effect of Hospital Volume on Outcomes of Patients with Occult Breast Cancer.
With limited data in regards to management, occult breast cancer (OBC) poses a challenging surgical scenario. Current surgical management includes axillary lymphadenectomy (ALND) with or without mastectomy. We sought to investigate the impact of hospital volume on surgical approach and survival outcomes of patients with OBC. Patients with cT0N+ breast cancer were selected from the National Cancer Data Base (NCDB, 2004-2014). Primary outcome was overall survival (OS), calculated using Kaplan-Meier methods compared according to hospital volume: community cancer center (CC), comprehensive community cancer center (COMP), and academic center (AC). Secondary outcome was the rate of modified radical mastectomy (MRM). We identified 574 patients with OBC, 11.1% were treated at a CC, 51.8% at a COMP, and 37.0% at an AC. Patients treated at CC had lower socioeconomic status compared with COMP or AC (23.1%, 14.1%, 19.3%; p = 0.005, respectively). There was no difference in access to radiation therapy (p = 0.888) or neoadjuvant chemotherapy (p = 0.221). Patients treated at CC had worse OS compared with COMP or AC (87.04, 105.29, 108.06 mo, p = 0.026, respectively). There was an increased rate of MRM at CC compared with COMP or AC (54.7%, 41.2%, 30.5%, p = 0.003, respectively). A direct association seems to exist between hospital volume and outcomes of patients with OBC. Patients with OBC treated at AC were more likely to undergo breast-conserving approaches and had better survival than those treated at CC.


Survival analysis.
This chapter introduces some fundamental results in survival analysis. We first describe what is censored failure time data and how to interpret the failure time distribution. Two nonparametric methods for estimating the survival curve, the life table estimator and the Kaplan-Meier estimator, are demonstrated. We then discuss the two-sample problem and the usage of the log-rank test for comparing survival distributions between groups. Lastly, we discuss in some detail the proportional hazards model, which is a semiparametric regression model specifically developed for censored data. All methods are illustrated with artificial or real data sets.


The impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected, opioid-dependent patients.
Opioid dependence is a major risk factor for HIV infection, however, the impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected opioid-dependent patients is unknown. We conducted a longitudinal analysis of 303 HIV-infected opioid-dependent patients initiating buprenorphine/naloxone treatment. Outcomes included self-reported past 90-day needle-sharing and non-condom use. We assessed trends over the 12 months using the Cochran-Armitage trend test. Using generalized estimating equations, after multiple imputation, we determined factors independently associated with needle-sharing and non-condom use, including time-updated variables. We then conducted a mediation analysis to determine whether substance use explained the relationship between time since treatment initiation and needle-sharing. Needle-sharing decreased from baseline to the fourth quarter following initiation of buprenorphine/naloxone (9% vs. 3%, p<0.001), while non-condom use did not (23% vs. 21%, p=0.10). HIV risk behaviors did not vary based on the presence of a detectable HIV-1 RNA viral load. Patients who were homeless and used heroin, cocaine/amphetamines or marijuana were more likely to report needle-sharing. Heroin use fully mediated the relationship between time since treatment initiation and needle-sharing. Women, patients who identified as being gay/lesbian/bisexual, those married or living with a partner and who reported heroin or alcohol use were more likely to report non-condom use. Older patients were less likely to report non-condom use. While buprenorphine/naloxone is associated with decreased needle-sharing among HIV-infected opioid-dependent patients, sexual risk behaviors persist regardless of viral load. Targeted interventions to address HIV risk behaviors among HIV-infected opioid-dependent populations receiving buprenorphine/naloxone are needed.


Isolation of Neutrophils from Larval Zebrafish and Their Transplantation into Recipient Larvae for Functional Studies.
Live imaging of neutrophils within optically transparent larval zebrafish has proved a powerful technique to investigate how specific gene products control neutrophil function. To resolve whether a gene contributes to neutrophil function in a cell-autonomous manner necessitates a way to examine gene-deficient neutrophils in an otherwise wild type background. To this end, here we describe methods to harvest fluorescent neutrophils from larval donor zebrafish and transplant them into age-matched recipients. We show that transplanted neutrophils can survive in recipient larvae for at least 3 days providing ample opportunity for functional studies. Focusing on bactericidal activity, we show that transplanted neutrophils phagocytose and kill live bacteria with similar kinetics to nontransplanted neutrophils, indicating that the transplantation process does not influence these neutrophil effector functions. Following the methods described here to transplant neutrophils between gene-deficient and wild type larval zebrafish will enable investigations into whether a gene's contribution to neutrophil function is cell-autonomous.


Complete genome sequence of Salinicoccus halodurans H3B36, isolated from the Qaidam Basin in China.
Salinicoccus halodurans H3B36 is a moderately halophilic bacterium isolated from a sediment sample of Qaidam Basin at 3.2 m vertical depth. Strain H3B36 accumulate N (α)-acetyl-α-lysine as compatible solute against salinity and heat stresses and may have potential applications in industrial biotechnology. In this study, we sequenced the genome of strain H3B36 using single molecule, real-time sequencing technology on a PacBio RS II instrument. The complete genome of strain H3B36 was 2,778,379 bp and contained 2,853 protein-coding genes, 12 rRNA genes, and 61 tRNA genes with 58 tandem repeats, six minisatellite DNA sequences, 11 genome islands, and no CRISPR repeat region. Further analysis of epigenetic modifications revealed the presence of 11,000 m4C-type modified bases, 7,545 m6A-type modified bases, and 89,064 other modified bases. The data on the genome of this strain may provide an insight into the metabolism of N (α)-acetyl-α-lysine.


The use of amniotic fluid discordance in the early second trimester to predict severe twin-twin transfusion syndrome.
The appropriate effectiveness of inter-twin amniotic fluid discordance (AFD) in the early second trimester for the prediction of severe twin-twin transfusion syndrome (TTTS) was evaluated. The largest AFD between 16 and 18 weeks' gestation was analyzed in correlation with TTTS development defined by polyhydramnios with a maximum vertical pocket (MVP) ≥8 cm combined with oligohydramnios with a MVP ≤2 cm using the receiver operating characteristics curve. All pregnancies were stratified according to an AFD cutoff, and perinatal outcomes were compared between two groups. A total of 223 twin monochorionic pregnancies met the inclusion criteria and 20 patients (8.9%) developed TTTS. An AFD ≥4 cm was calculated to be the optimal point of demarcation to predict subsequent TTTS. The sensitivity and specificity of this AFD cutoff for the development of TTTS were 70 and 97%, respectively. An AFD ≥4 cm was associated with a significantly increased risk of the development of TTTS (70 vs. 2.9%; p < 0.01). Those pregnancies with AFD tended to deliver at an earlier gestational age and were also significantly associated with intrauterine fetal deaths. The AFD between monochorionic diamniotic twins in the early second trimester may be useful for the prediction of severe TTTS development.


A quality improvement study of the placement and complications of double-lumen endobronchial tubes.
To assess the complications of conventional and fiberoptic endobronchial intubations using reusable (Leyland, London) and disposable (Rüsch, Waiblinger, Germany; Sheridan, Argyle, NY) double-lumen tubes (DLTs), endobronchial intubations occurring over a 12-month period were prospectively studied at this hospital. Residents working with staff anesthesiologists placed either left or right reusable (Leyland) or disposable (Rüsch or Sheridan) DLTs. The DLT used, the use of fiberoptic bronchoscopy (FOB), findings at FOB if used during the intubation or operation, and complications occurring during the case (SpO2 < 90%, peak inflation pressure > 40 cm H2O, air trapping, poor lung isolation, and airway trauma) were recorded. Two hundred thirty-four intubations were analyzed (102 right, 132 left; 70 Leyland reusable DLTs, 66 Rüsch disposable tubes, and 98 Sheridan tubes). Physical signs alone were used to confirm tube position more frequently when Leyland tubes were placed compared with disposable tubes (79% v 39%, P < 0.0001). Rüsch and Sheridan DLTs had similar rates of conventional placement. Nineteen percent of reusable tubes and 44% of disposable tubes required position adjustments using FOB during the initial intubation (P = 0.0002). Disposable tubes also more commonly required readjustment using FOB during the operation (30% v 7%, P < 0.0005). Complications occurred in 42/234 patients (18%). The frequency of specific complications was: decreased SpO2, 9%; increased airway pressures, 9%; poor lung isolation, 7%; air trapping, 2%, and airway trauma, 0.4%. Right-sided Sheridan DLTs had a statistically higher incidence of malposition, resulting in poorer lung isolation.(ABSTRACT TRUNCATED AT 250 WORDS)


Meiofaunal and bacterial community response to diesel additions in a microcosm study.
Effects of low PAH-containing diesel were studied in a 60-day microcosm experiment at PAH concentrations 130, 1300 and 13,000μg/kg sediment. Nutrient fluxes, potential nitrification and meiofaunal community composition were analysed at three time points. Changed ∑NOx-fluxes indicated reduced sediment nitrification in Medium and High with time, in agreement with lowered potential nitrification rates in all treatments. Reduction in silicate and phosphate fluxes over time suggested severe effects on activity of meiofauna. Reduced activity increased the anoxic sediment layer, which could have contributed to the changed ∑NOx-fluxes. There were significant differences in meiofaunal community composition after 30 and 60days in Medium and High. Changes were due to increasing numbers of harpacticoids and the foraminiferan group Rotaliina, as well as decreasing numbers of Nematodes and the foraminiferan group Reophax. In spite of the low PAH-level, small additions of this diesel can still have pronounced effects on meiofaunal and bacterial communities.


Nanomaterials in membrane bioreactors: Recent progresses, challenges, and potentials.
The use of nanomaterials (NMs) in the fabrication and modification of membranes as well as the coupling of nanomaterial-based processes with membrane processes have been attracted many researchers today. The NMs due to a wide range of types, different chemistry, the possibility of various kinds of functionality, different properties like antibacterial activity, hydrophilicity, and large surface area were applied to enhance the membrane properties. In the membrane bioreactors (MBRs) as a highly successful process of membrane technology in wastewater treatment, the NMs have been applied for improving the efficiency of MBR process. This review assessed the application of NMs both as the modifiers of membrane and as the effective part of hybrid techniques with MBR system for wastewater treatment. The efficiency of NMs blended membranes in the MBR process has been reviewed in terms of antifouling and antibacterial improvement and removal performance of the pollutants. Novel kinds of NMs were recognized and discussed based on their properties and advantages. The NMs-based photocatalytic and electrochemical processes integrated with MBR were reviewed with their benefits and drawbacks. In addition, the effect of the presence of mobilized NPs in the sludge on MBR performance was surveyed. As a result of this review, it can be concluded that nanomaterials generally improve MBR performance. The high flux and antifouling properties can be obtained by adding nanomaterials with hydrophilic and antibacterial properties to the membrane, and further studies are required for photocatalytic NMs applications. In addition, this review shows that the low amounts of NMs in the membrane structure could have an effective influence on the MBR process. Besides, since many studies in the literature are carried out at the laboratory scale, it is thought that pilot and real-scale studies should be carried out to obtain more reliable data.


ECGs in Critical Care Cardiology: Do Not Miss That Myocardial Infarction.
This paper provides clinical cases of acute myocardial infarction that do not show ST-segment elevation on 12-lead electrocardiogram, but should be clinically treated as ST-segment elevation myocardial infarction with early diagnostic coronary angiogram followed by appropriate strategy of revascularization. (Level of Difficulty: Beginner.).


Potentiation of halomethane hepatotoxicity: chlordecone and carbon tetrachloride.
The propensity for chlordecone to potentiate hepatotoxicity of CCl4 and some related analogs (CHCl3 and CBrCl3) has been well established. The interaction results in potentiation of halomethane hepatotoxicity at incredibly small, nontoxic levels of chlordecone and these halomethanes. Biological effects of such interactions include extensive hepatotoxicity characterized by total hepatic failure as determined by histopathological alterations, hepatic dysfunction, elevation of serum enzymes, and perturbation of related biochemical parameters. The chlordecone + CCl4 interaction occurs in animals of both sexes and is characterized by profoundly potentiated lethality. Close structural analogs of chlordecone such as mirex and photomirex do not share the propensity of chlordecone to potentiate halomethane toxicity. The mechanism of this potentiation of halomethane hepatotoxicity has eluded several investigations. Induction of microsomal P-450 by chlordecone and greater lipid peroxidation appear inadequate to explain the powerful potentiation of toxicity. Time-course studies in which liver tissue was examined 1 to 36 hr after CCl4 administration to chlordecone treated animals revealed possible mechanisms. It appears that a greater bioactivation of CCl4 in chlordecone treated animals resulted in an initial potentiation of toxic events in the liver cells. While animals receiving a normally nontoxic dose of CCl4 alone demonstrate repair and renovation of liver tissue as revealed by greatly increased mitotic index after 12 hours, such a renovation process is totally suppressed in animals exposed to chlordecone. Thus, a combination of initial greater injury along with prevention of hepatocellular repair and renovation appears to play a key role in the potentiation of liver injury. The greater initial liver injury is consistent with enhanced metabolism and bioactivation of CCl4 in chlordecone exposed animals. The mechanism of suppressed cellular mitosis is less clearly understood. Recent studies have revealed a greater perturbation of intracellular Ca2+ homeostasis in chlordecone treated animals and this observation is consistent with continued destruction and cellular damage. These observations point to more than a single factor involved as underlying mechanisms and two such mechanisms are consistent with the available information. First, chlordecone induction of a specific form of P-450 capable of greater bioactivation of CCl4. Second, chlordecone sensitization of hepatocellular plasma membrane for excessive accumulation of intracellular Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)


Higher age and present injury at the start of the season are risk factors for in-season injury in amateur male and female football players-a prospective cohort study.
To describe the injury prevalence, injury pattern, and potential baseline risk factors for injuries in male and female adolescent and adult amateur football players. This prospective study followed adolescent and adult amateur football players over one season March-October 2020. The study was completed by 462 players (130 men, age 20.0 ± 5.7, 14-46 years) who answered a baseline survey and a weekly web survey during the season. A total of 1456 weekly surveys were registered from males and 5041 from females. Injuries were recorded with the Oslo Sports Trauma Research Center Overuse Injury Questionnaire (OSTRC-O2). Potential baseline risk factors (age, performance of strength/conditioning training, participation in other sports, perceived importance of sporting success, self-rated training and match load, perceived balance between training/match load and recovery, previous/present injury at start of season, and injury beliefs) and their association with injury were analysed with Poisson regressions within each sex. Males reported 95 injuries (262 injury weeks, weekly prevalence 18.0% (95% CI 16.1-20.1)) and females 350 injuries (1206 injury weeks, weekly prevalence 23.9% (95% CI 22.8-25.1)). Gradual-onset injuries accounted for 57% of the injuries in males and 66% in females. For males, substantial injuries were most common in the hip/groin (weekly prevalence 3.8%), ankle (2.1%), posterior thigh (2.0%), and knee (2.0%); and for females, in the knee (4.3%), ankle (2.5%), and lower leg/Achilles tendon (2.0%). Significant risk factors for injury were higher age (rate ratio males 1.05 per year increase (95% CI 1.02-1.08), females 1.03 (95% CI 1.01-1.05)), and present injury at baseline (males 1.92 (95% CI 1.27-2.89), females 1.58 (95% CI 1.19-2.09)). At any given week, almost one in five male and one in four female amateur football players reported new or ongoing injuries. Hip/groin injuries were more frequent in males, while female players had a higher prevalence of knee injuries. Older players and those with an existing injury at the start of the season were more prone to new injury during the season. Rehabilitation of pre-season injury and complaints are key to reduce the injury burden in amateur football. Level II. Trial registration number NCT04272047, Clinical trials.


Investigation of the pH-dependent aggregation mechanisms of GCSF using low resolution protein characterization techniques and advanced molecular dynamics simulations.
Granulocyte-colony stimulating factor (GCSF) is a widely used therapeutic protein to treat neutropenia. GCSF has an increased propensity to aggregate if the pH is increased above 5.0. Although GCSF is very well experimentally characterized, the exact pH-dependent aggregation mechanism of GCSF is still under debate. This study aimed to model the complex pH-dependent aggregation behavior of GCSF using state-of-the-art simulation techniques. The conformational stability of GCSF was investigated by performing metadynamics simulations, while the protein-protein interactions were investigated using coarse-grained (CG) simulations of multiple GCSF monomers. The CG simulations were directly compared with small-angle X-ray (SAXS) data. The metadynamics simulations demonstrated that the orientations of Trp residues in GCSF are dependent on pH. The conformational change of Trp residues is due to the loss of Trp-His interactions at the physiological pH, which in turn may increase protein flexibility. The helical structure of GCSF was not affected by the pH conditions of the simulations. Our CG simulations indicate that at pH 4.0, the colloidal stability may be more important than the conformational stability of GCSF. The electrostatic potential surface and CG simulations suggested that the basic residues are mainly responsible for colloidal stability as deprotonation of these residues causes a reduction of the highly positively charged electrostatic barrier close to the aggregation-prone long loop regions.


Comparison of three methods to estimate dental age in children.
In 1973, Demirjian and colleagues introduced a staging for tooth mineralization. Staging of the teeth of the left mandible generates a dental maturity score and an estimate of dental age. An update of this method was published in 2001 by Willems and colleagues. The London Atlas (2008) is another method used to assess dental age. This study compared the precision of these three methods for forensic age estimation. A total of 500 panoramic images of 251 boys and 249 girls aged 6-16 years had dental maturity evaluated by the same observer using the London Atlas and the methods of Demirjian and Willems. Individuals with syndromes potentially affecting dental maturation were excluded. The three methods were compared with respect to their precision in estimating chronological age. Age estimates using Willems' method were significantly more precise than those obtained using Demirjian's method, while estimates obtained using the London Atlas method were comparable with both the others. The highest precision was obtained using the average of age estimates from Willems' method and the London Atlas. To estimate age in individuals suspected of being below 16 years of age, we suggest first applying the London Atlas then computing age from the Demirjian stages of particular teeth using Willems' method, and finally using the average age estimate of both methods. Combining the London Atlas and Willems' scoring method provides more precise estimates of dental age than the current practice of applying a single preferred method.


Engineered upconversion nanocarriers for synergistic breast cancer imaging and therapy: Current state of art.
Breast cancer is the most common type of cancer in women and is the second leading cause of cancer-related deaths worldwide. Early diagnosis and effective therapeutic interventions are critical determinants that can improve survival and quality of life in breast cancer patients. Nanotheranostics are emerging interventions that offer the dual benefit of in vivo diagnosis and therapeutics through a single nano-sized carrier. Rare earth metal-doped upconversion nanoparticles (UCNPs) with their ability to convert near-infrared light to visible light or UV light in vivo settings have gained special attraction due to their unique luminescence and tumor-targeting properties. In this review, we have discussed applications of UCNPs in drug and gene delivery, photothermal therapy (PTT), photodynamic therapy (PDT) and tumor targeting in breast cancer. Further, present challenges and future opportunities for UCNPs in breast cancer treatment have also been mentioned.


Veterinary Student Knowledge and Attitudes about Swine Change after Lectures and a Farm Visit.
Veterinary schools are facing the challenge of increasing animal welfare (AW) training while also attracting future practitioners to livestock medicine. Both objectives may be better achieved through farm visits early in veterinary training. First year veterinary students at the University of Minnesota (n = 103) were surveyed during the Spring 2019 Professional Development II course to document their knowledge, attitudes, and values relative to pigs, AW, and the industry before and after classroom and online lectures and a visit to a farrow-to-wean farm. Quantitative (Kruskal-Wallis, Kendall tau-c and Chi-Square) and qualitative (content analysis) analyses were used to identify shifts in knowledge and attitudes and associations with demographics and use of the AW values of biological functioning, affective state, and natural living. Most students were female (85.4%), from urban/suburban backgrounds (68.9%), and did not wish to work with livestock (66.0%). Knowledge scores (p <.05) and attitudes toward pigs (p = .0152) improved after visiting the farm. Satisfaction with AW on most commercial farms shifted after the farm visit (p = .0003), with those valuing biological functioning becoming more satisfied (p = .0342). In contrast, students who visited the farm when enrichment was provided were more dissatisfied compared to those who toured the farm without enrichment (p = .0490). Those referencing natural living (p = .0047) rated the toured farm as a poorer steward of welfare. Students' AW concerns included behavioral restriction in individual stalls and injury and lameness in group pens. Farm visits are an important tool in veterinary education, but may result in segmentation in student knowledge and attitudes relative to livestock welfare.


Hemoptysis due to fungus ball after tuberculosis: A series of 21 cases treated with hemostatic radiotherapy.
In patients who are not amenable to surgical resection (cavernostomy), it is difficult to achieve palliation of hemoptysis from pulmonary aspergilloma. There are only 9 cases with a short follow-up that have reported the use of radiotherapy for hemoptysis in this scenario. A retrospective series of 21 patients with chronic necrotizing pulmonary aspergillosis were treated with radiotherapy (20 Gray) from 1990 to 2002. The outcome measures were the period from tuberculosis treatment to the onset of hemoptysis, hemoptysis resolution rate, change in Zubrod performance status after 30 days of the completion of radiotherapy, local failure-free survival, and overall survival. The median time between tuberculosis treatment and the onset of hemoptysis due to aspergilloma was 9 years. After radiotherapy, general status improved and the hemoptysis resolved in all patients. During the follow-up period, 4 failures occurred, with a 5-year local failure-free survival rate of 82 % and a 5-year overall survival rate of 59 %. Of these failures, 2 patients died due to recurrence of the hemoptysis, and 2 were rescued (using cavernostomy and reirradiation). The presence of chronic obstructive pulmonary disease (COPD) (p = 0.021) and female gender (p = 0.032) were negatively associated with overall survival. None of the variables was related to local control. Based on these long-term data, radiotherapy is a potential option for controlling bleeding due to fungus balls. Female patients and COPD were associated with lower survival.


Surgery in intractable epilepsy-physicians' recommendations and patients' decisions.
To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.


Intestinal perforation in very low birth weight infants: growth and neurodevelopment at 1 year of age.
To compare growth and neurodevelopment in surviving very low birth weight (VLBW) infants with an intestinal perforation (IP) caused by necrotizing enterocolitis (NEC) versus spontaneous intestinal perforation (SIP). Retrospective, observational cohort study. Infants born between January 1996 and December 1999 with birth weight <1500 g and a diagnosis of intestinal perforation were identified and data extracted from NICU, surgical and hospital databases. IP was identified in 62 of 1357 VLBW infants (5%); 39 infants (63%) had surgical NEC and 23 (37%) had SIP. Among survivors, 21/28 with surgical NEC (75%) and 13/18 with SIP (72%) returned for follow-up. At 1-year adjusted age, there were no differences in growth parameters but the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) were lower in survivors with NEC versus SIP (mean difference in MDI=15; 95% confidence limits=3, 28; p=0.02; mean difference in PDI=14; 95% confidence limits=0.4, 28; p=0.04). Intestinal perforation caused by NEC, as compared to SIP, is associated with worse neurodevelopmental outcome at 1 year.


Viscoelastic properties of elastomeric chains: an investigation of pigment and manufacturing effects.
Orthodontic elastomeric chains are commercially available in various colors from many manufacturers. In this study, we investigated the viscoelastic properties of elastomeric chains using dynamic mechanical analysis to perform color and brand comparisons. Ten colors of Sunburst chains (GAC International, Bohemia, NY) were selected for the color study. Three colors of Sunburst, Bobbin Alastik (3M Unitek, Monrovia, Calif), and Energy (Rocky Mountain Orthodontics, Denver, Colo) chains were selected for the brand study. Nine specimens of each type were measured and tested. Dynamic mechanical analysis was performed at room temperature at 8 frequencies ranging from 0.125 to 16.0 Hz. Three variables (storage stiffness, loss stiffness, and tan δ) were analyzed by using repeated-measures analysis of variance (ANOVA) and pairwise t tests, comparing all frequencies for each specimen type and all specimen types for each frequency (with Bonferroni corrections). Significance was set at α = 0.05. Significant differences were found among all specimen dimensions, all frequencies, and all 3 dynamic mechanical analysis variables in both the color and brand studies. Comparisons focused on tan δ, which does not depend on specimen dimensions as do storage stiffness and loss stiffness. Statistically significant differences in tan δ values among colors were relatively small, so the clinical significance is questionable and requires further investigation. Differences in tan δ values among brands were greater and more likely to be clinically significant. Further studies are needed to relate viscoelastic properties to force decay.