The association between serum estradiol levels and sperm DNA integrity.
In men from the general population, BMI has been associated with a lower sperm DNA fragmentation index (DFI). We wondered whether this could be due to estradiol, which is associated with BMI and reported important for sperm function. Our objective was to investigate the association between estradiol and DFI. In 2008-2010, we recruited 284 young men from the general population to deliver samples of semen and blood and answer questionnaires. Serum concentrations of reproductive hormones and DFI were analyzed, the latter using the Sperm Chromatin Structure Assay. Associations were studied using general linear models. The first model utilized metric values of estradiol, whereas the second model compared men with high and low levels, dichotomized by the median value. A possible interaction between estradiol and testosterone was also examined. When investigating metric estradiol levels and DFI, an inverse association was seen without adjustments (p = .02), but the statistical significance was lost at adjustments for potential confounders (p = .08). Men with lower estradiol levels (<88 pmol/L, mean 71 pmol/L) had a statistically significantly higher DFI than men with higher levels of estradiol (≥88 pmol/L, mean 110 pmol/L). Mean ratio difference was 1.21 (p = .002) without adjustments and 1.18 (p = .01) with adjustments. A statistically significant difference in DFI was observed in men with testosterone levels below median when comparing high and low estradiol (p < .001). This study supports the idea that serum estradiol levels are protective for sperm DNA integrity, at least at lower testosterone levels.


Human Infections by Non-Rodent-Associated Hantaviruses in Africa.
Various hantaviruses have been discovered in unconventional hosts (shrews and bats) in Africa. Up to now, it was unknown whether these viruses pose a threat for human health. In this study, using newly established serological assays, we demonstrated evidence of shrew-borne hantavirus infections in humans from Côte d'Ivoire and Gabon.


Periodic Operation of a Dynamic DNA Origami Structure Utilizing the Hydrophilic-Hydrophobic Phase-Transition of Stimulus-Sensitive Polypeptides.
Dynamic DNA nanodevices are designed to perform structure-encoded motion actuated by a variety of different physicochemical stimuli. In this context, hybrid devices utilizing other components than DNA have the potential to considerably expand the library of functionalities. Here, the reversible reconfiguration of a DNA origami structure using the stimulus sensitivity of elastin-like polypeptides is reported. To this end, a rectangular sheet made using the DNA origami technique is functionalized with these peptides and by applying changes in salt concentration the hydrophilic-hydrophobic phase transition of these peptides actuate the folding of the structure. The on-demand and reversible switching of the rectangle is driven by externally imposed temperature oscillations and appears at specific transition temperatures. Using transmission electron microscopy, it is shown that the structure exhibits distinct conformational states with different occupation probabilities, which are dependent on structure-intrinsic parameters such as the local number and the arrangement of the peptides on the rectangle. It is also shown through ensemble fluorescence resonance energy transfer spectroscopy that the transition temperature and thus the thermodynamics of the rectangle-peptide system depends on the stimuli salt concentration and temperature, as well as on the intrinsic parameters.


Intrinsic and extrinsic regulation of mammalian hematopoiesis in the fetal liver.
The fetal liver (FL) is an important structure in expansion and differentiation of hematopoietic stem cells (HSC), but despite this little is known about the exact mechanisms in which FL hematopoiesis takes place. Primitive hematopoiesis gives way to definitive hematopoiesis at 12.5 dpc in mice and the process is regulated by a number of intrinsic and extrinsic factors. Intrinsic regulations are intracellular processes that have been reported to be important in the initiation of definitive hematopoiesis. Several structures are involved with extrinsic regulations of hematopoiesis within the FL, including hepatoblasts and liver sinusoidal endothelial cells (LSEC). Hepatoblasts and endothelial cells comprise separate niches involved in the extrinsic regulation of hematopoiesis. Studies have shown that co-cultures with fetal liver stromal cells can promote the expansion of erythroid cells, although the way in which stromal cells do this is still unknown. Understanding the mechanisms in which hematopoiesis is regulated in the FL could lead to the production of novel therapies involving the safe and reliable transplantation of HSCs to patients with blood and bone marrow complications. This review aims to summarize the current state of knowledge about the regulation of hematopoiesis specifically within the FL.


Phosphorescent polymeric nanoparticles by coordination cross-linking as a platform for luminescence imaging and photodynamic therapy.
Water-soluble phosphorescent polymeric nanoparticles with an average diameter of approximately 100 nm were synthesized by a coordination cross-linking reaction. The pyridine blocks in poly(4-vinyl pyridine-b-ethylene oxide) (P4VP-b-PEO) were cross-linked by the iridium chloride-bridged dimer in DMF solution. Owing to the presence of an iridium complex with different ligands in the core of the polymeric nanoparticles, NP-1, NP-2, and NP-3 showed bright green, yellow, and red phosphorescence, respectively. PEG chains in the shell gave the polymeric nanoparticles solubility and biocompatibility, which was confirmed by an MTT assay using HeLa cells as a model cancer cell line. The flow cytometry and laser confocal fluorescence microscopy results revealed NP-2, as an example, could be effectively uptaken by HeLa cells. Therefore, these polymeric nanoparticles can be used as luminescent probes for living cells. In addition, (1) O2 could be effectively generated in the presence of NP-2 upon irradiation with visible light (λ>400 nm, 300 mW cm(-2) ), which was confirmed by a clear decrease in the fluorescence intensity of 9,10-dimethylanthracene (DMA). After incubation with NP-2 at a concentration of 200 μg mL(-1) for 6 h, approximately 90 % of HeLa cells were effectively ablated upon irradiation with visible light for only 10 min, indicating the potential for photodynamic therapy with polymeric nanoparticles.


Historical development of local therapy of psoriasis vulgaris.
Throughout the history people have used various remedies for the treatment of psoriasis. Some of them were bizarre, some ineffective and harmful, and some have survived until today and are still in use. Salicylic acid, anthralin, coal tar, corticosteroids, vitamin D3 analogues, retinoids must be mentioned as remarkably effective ones. Phototherapy and laser therapy are both promising techniques, as well as immunomodulators. Underlying mechanisms of psoriasis and mode of action of therapeutics that have been elucidated over the time allowed for the development of more potent and promising therapy of psoriasis.


Time-dependent control of hole-opening degree of porous ZnO hollow microspheres.
Well-designed, monodispersed porous ZnO hollow microspheres with controlled hole-opening were successfully synthesized by a facile two-step solution route at low temperature. The hollow microspheres having average diameter of 3-4 μm showed time-dependent hole-opening, i.e. 4-100% for 15-75 min. The hole-opening percentage increases linearly with time until complete opening. The ZnO hollow microspheres also exhibited a high surface area (34 m(2) g(-1)), a large pore volume (0.19 cm(3) g(-1)) and an average pore diameter of 3.8 nm. A plausible growth mechanism for the formation of ZnO hollow microspheres was also proposed.


Adiposity in relation to colorectal adenomas and hyperplastic polyps in women.
To examine whether BMI is independently related to colorectal adenomas and hyperplastic polyps. We conducted a cross-sectional study among 1,420 asymptomatic women aged 40-79 years who had undergone complete colonoscopy. Logistic regression was used to estimate the odds ratios (OR) and the corresponding 95% confidence intervals (CI) of adenomas and hyperplastic polyps. We identified 953 women (67.1%) with no polyps, 292 (20.6%) with adenomas, and 175 (12.3%) with hyperplastic polyps. Among those with polyps, 75 women (5.3% of total women) were classified as having both adenomas and hyperplastic polyps. After adjusting for potential risk factors for colorectal cancer, BMI was related to increased risk of adenomas (OR comparing obese to normal weight women = 1.57; 95% CI = 1.07-2.29). Further, BMI was associated with enhanced risk of hyperplastic polyps (OR = 3.76; 95% CI = 2.35-6.01) and the combination of adenomas and hyperplastic polyps (OR = 2.84; 95% CI = 1.41-5.72). Excess body mass is positively related to colorectal adenomas and hyperplastic polyps, particularly when both kinds of polyps are present in combination. Future studies should continue to delineate the possible differences in potential risk factors between colorectal adenomas and hyperplastic polyps. Such work should help further elucidate the possible causes of colorectal cancer.


[Long-term outcomes of Chiari osteotomy for Legg-Calvé-Perthes disease in children].
To explore long-term outcomes of Chiari osteotomy for Legg-Calvé-Perthes disease in children with type Catterall III or IV, and to analyze clinical effect of osteotomy angle on clinical and radiographic results. From March 2005 to July 2013, 26 children with Legg-Calvé-Perthes disease with type Catterall III or IV were treated by Chiari osteotomy, including 17 males and 9 females, aged from 4 to 13 years old with an average of (8.9±2.6) years old. Children were divided into low osteotomy angle group and high osteotomy angle group. according to osteotomy angle. There were 10 children in low osteotomy angle group with an osteotomy angle of 10 degrees, including 8 boys and 2 girls, aged from 4 to 13 years old with an average of (9.2±3.3) years old; while there were 16 children in high osteotomy angle group with an osteotomy angle of 15 degress, including 9 boys and 7 girls, aged from 6 to 12 years old with an average of (8.8±2.1) years old. HHS score before operation and at the latest follow-up were recorded to observe clinical results. CE angle of hip joint, acetabular index, Sharp angle, Shenton's line continuity, femoral head coverage, acetabular depth ratio were recorded to compare radiographic results. Stulberg classification was analyzed to compare reshaping ability of femoral head. Twenty-six children were followed up for 4.5 to 12.0 years with an average of (7.9±1.8) years. All incisions were healed at stage I for 10 to 14 days, with an average of(12.3±1.1) days. No inflammation, skin necrosis and injury of vessel and nerve occurred. All osteotomies achieved bone union for 8 to 13 weeks, with an average of(9.8±1.4) weeks. HHS score increased from 75.8±6.5 before operation to 93.5±2.5 at the latest follow-up in low osteotomy angle group(P<0.05), and form 77.6±6.2 to 97.8±1.6 in high osteotomy angle group (P<0.05). HHS score of high osteotomy angle group at the latest follow-up was higher than that of low osteotomy angle group (P<0.05). The acetabular index decreased from (10.1±2.5)° before operation to (4.5±1.3)° at the latest follow-up in low osteotomy angle group (P<0.05), and from (10.7±3.3)° before operation to (2.0±1.1)° in high osteotomy angle group (P<0.05). The acetabular index of high osteotomy angle group at the latest followup was better than low osteotomy angle group(P<0.05). There was no significant difference in CE angle, Sharp angle, Shenton's continuity, femoral head coverage, acetabular depth ratio between two groups. According to Stulberg classification, the femoral head reshaping ability in high osteotomy angle group was better than that of low osteotomy angle group(P<0.05). Chiari osteotomy with 15° for Legg-Calvé-Perthes disease in children with type Catterall III or IV could effectively decrease index of acetabulum, and helpful for femoral head reshaping ability, then in further improve clinical effects.


Structure-function relationships of wheat flavone O-methyltransferase: Homology modeling and site-directed mutagenesis.
Wheat (Triticum aestivum L.) O-methyltransferase (TaOMT2) catalyzes the sequential methylation of the flavone, tricetin, to its 3'-methyl- (selgin), 3',5'-dimethyl- (tricin) and 3',4',5'-trimethyl ether derivatives. Tricin, a potential multifunctional nutraceutical, is the major enzyme reaction product. These successive methylations raised the question as to whether they take place in one, or different active sites. We constructed a 3-D model of this protein using the crystal structure of the highly homologous Medicago sativa caffeic acid/5-hydroxyferulic acid O-methyltransferase (MsCOMT) as a template with the aim of proposing a mechanism for multiple methyl transfer reactions in wheat. This model revealed unique structural features of TaOMT2 which permit the stepwise methylation of tricetin. Substrate binding is mediated by an extensive network of H-bonds and van der Waals interactions. Mutational analysis of structurally guided active site residues identified those involved in binding and catalysis. The partly buried tricetin active site, as well as proximity and orientation effects ensured sequential methylation of the substrate within the same pocket. Stepwise methylation of tricetin involves deprotonation of its hydroxyl groups by a His262-Asp263 pair followed by nucleophilic attack of SAM-methyl groups. We also demonstrate that Val309, which is conserved in a number of graminaceous flavone OMTs, defines the preference of TaOMT2 for tricetin as the substrate. We propose a mechanism for the sequential methylation of tricetin, and discuss the potential application of TaOMT2 to increase the production of tricin as a nutraceutical. The single amino acid residue in TaOMT2, Val309, determines its preference for tricetin as the substrate, and may define the evolutionary differences between the two closely related proteins, COMT and flavone OMT.


Posterior dislocation in a voluntary subluxator: a case report.
Posterior instability of the shoulder is an uncommon occurrence. Its etiology has been classified as traumatic or atraumatic and its type as voluntary (individual can subluxate the shoulder posteriorly) or involuntary. Typically, patients with posterior voluntary instability do not have a history of trauma, can be treated successfully with physical therapy; and undergo surgery if the instability becomes symptomatic or develops an involuntary component. We present a patient with voluntary posterior subluxation who developed a symptomatic posterior instability after a traumatic event. This patient was unable to return to his preinjury function despite nonoperative interventions, including rehabilitation, and required operative treatment of his posterior labrum lesion. This patient had a rare combination of voluntary, atraumatic instability that coexisted with traumatic posterior shoulder instability. This case emphasizes the importance of recognizing this constellation of instability patterns and documents that traumatic posterior instability, even in the presence of preexisting voluntary posterior subluxations, may require operative intervention in young, active individuals.


Role of dyslipidemia in the development of early-onset preeclampsia.
Preeclampsia (PE) is a gestational-related disease presented with hypertension, peripheral edema, and proteinuria after 20 weeks of gestation. In PE, there are various metabolic changes like dyslipidemia. In addition, both PE and dyslipidemia are associated with changes of platelet indices. Thus, objective of the current study was to illustrate the potential role of dyslipidemia and platelet changes in pregnant women with PE. This case-control study involved 37 preeclamptic pregnant women as compared to 24 healthy pregnant women as controls. Blood pressure profile, lipid profile, proteinuria, and platelet indices were measured. Blood pressure profile was higher in preeclamptic pregnant women as compared to the controls (P < 0.01). There was a significant dyslipidemic status in preeclamptic pregnant women compared with the controls (P < 0.01). Platetetcrit (PCT) and platelet count (PC) were lower in preeclamptic pregnant women compared with the controls (P = 0.001). On the other hand, platelet distribution width (PDW), mean platelet volume (MPV), and platelet-large cell ratio (P-LCR) were higher in the pregnant women with PE as compared with the controls (P = 0.001). PCT and PC were insignificantly linked, while P-LCR, MPV and PDW were significantly correlated with total cholesterol, triglyceride, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio, systolic blood pressure, DBP, and MAP in preeclamptic patients compared with women of normal pregnancy. Both dyslipidemia and alterations in the platelet indices are correlated with blood pressure profile in PE. High MPV and PDW in association with high LDL/HDL ratio in pregnant women herald risk of PE.


Systemic dendrimer-drug treatment of ischemia-induced neonatal white matter injury.
Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead to white matter injury that is a precursor for a number of neurological diseases, including cerebral palsy (CP) and autism. Neuroinflammation, mediated by activated microglia and astrocytes, is implicated in the pathogenesis of neonatal brain injury. Therefore, targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes in models of perinatal white matter injury. In this work, we use a mouse model of ischemia-induced neonatal white matter injury to study the biodistribution of generation 4, hydroxyl-functionalized polyamidoamine dendrimers. Following systemic administration of the Cy5-labeled dendrimer (D-Cy5), we demonstrate dendrimer uptake in cells involved in ischemic injury, and in ongoing inflammation, leading to secondary injury. The sub-acute response to injury is driven by astrocytes. Within five days of injury, microglial proliferation and migration occurs, along with limited differentiation of oligodendrocytes and oligodendrocyte death. From one day to five days after injury, a shift in dendrimer co-localization occurred. Initially, dendrimer predominantly co-localized with astrocytes, with a subsequent shift towards microglia. Co-localization with oligodendrocytes reduced over the same time period, demonstrating a region-specific uptake based on the progression of the injury. We further show that systemic administration of a single dose of dendrimer-N-acetyl cysteine conjugate (D-NAC) at either sub-acute or delayed time points after injury results in sustained attenuation of the 'detrimental' pro-inflammatory response up to 9days after injury, while not impacting the 'favorable' anti-inflammatory response. The D-NAC therapy also led to improvement in myelination, suggesting reduced white matter injury. Demonstration of treatment efficacy at later time points in the postnatal period provides a greater understanding of how microglial activation and chronic inflammation can be targeted to treat neonatal brain injury. Importantly, it may also provide a longer therapeutic window.


Is pinning in situ a safe procedure for slipped capital femoral epiphysis?
This report reviews the results of 37 patients with 46 involved hips treated with pinning for slipped capital femoral epiphysis. Particular attention was given to incidence of complications, including avascular necrosis, chondrolysis, and penetration of the joint. Of 46 hips with 1-year follow-up, there were no cases of chondrolysis. Of 23 hips with 2-year follow-up, there was only 1 case of avascular necrosis. Pin penetration, recognized at the time of surgery, produced no significant sequelae. Pinning can produce satisfactory results without a significant incidence of major complication.


Contact lens-associated nocardial necrotizing scleritis.
A 52 year-old, contact lens-wearing man presented with progressive right eye pain and redness for one month. He had been evaluated and treated for necrotizing scleritis by multiple eye care specialists prior to presentation. He underwent a complete systemic work-up for both autoimmune and infectious causes of scleritis, including a culture. The culture revealed heavy growth of Nocardia asteroides complexes. The patient was treated with topical amikacin and oral Bactrim. Following several weeks of antibiotic treatment, the patient's infection resolved completely, and his visual acuity returned to baseline status. Nocardia is a rare but potentially devastating cause of necrotizing scleritis that may affect contact lens wearers without an associated keratitis. Prompt recognition and early treatment with appropriate antimicrobial agents are critical to achieve a favorable outcome.


[Pre-ejection flow in the left ventricular outflow tract: a pulsed Doppler echocardiographic study].
Pre-ejection flow (PEF) has been recognized as the flow of short duration toward the cardiac base in the left ventricular outflow tract. In the present study, PEF was analyzed by pulsed Doppler echocardiography to determine the contribution of left ventricular contraction to the genesis of PEF. The study subjects consisted of 20 patients with lone atrial fibrillation (Af) and 30 patients with premature ventricular contractions (PVC) without other cardiovascular diseases. Phonocardiogram and electrocardiogram were simultaneously recorded with Doppler signal of PEF. PEF was clearly detected in only 18 patients with PVC; in the remaining 12, it was not recorded or could not be differentiated from the signals of the preceding left ventricular diastolic filling. Results were as follows: 1. PEF in the cases with sinus rhythm appeared before the Q wave; whereas, it appeared after the Q wave in the cases with Af or PVC, and the peak of PEF coincided with the first heart sound on the phonocardiogram. 2. The duration of PEF was 93.6 +/- 15.4 msec in sinus rhythm, 60.6 +/- 14.2 msec in Af, and 87.5 +/- 19.4 msec in PVC. 3. Peak velocities of PEF in Af and PVC were significantly less than peak velocity of PEF in sinus rhythm. 4. Peak velocity of PEF in PVC with left bundle branch block tended to be less than that in PVC with right bundle branch block.(ABSTRACT TRUNCATED AT 250 WORDS)


Simplified estimates of ion-activity products of calcium oxalate and calcium phosphate in mouse urine.
This study aimed at formulating simplified estimates of ion-activity products of calcium oxalate (AP(CaOx)) and calcium phosphate (AP(CaP)) in mouse urineto find the most important determinants in order to limit the analytical work-up. Literature data on mouse urine composition was used to determine the relative effect of each urine variable on the two ion-activity products. AP(CaOx) and AP(CaP) were calculated by iterative approximation with the EQUIL2 computerized program. The most important determinants for AP(CaOx) were calcium, oxalate and citrate and for AP(CaP) calcium, phosphate, citrate, magnesium and pH. Urine concentrations of the variables were used. A simplified estimate of AP(CaOx) (AP(CaOx)-index(MOUSE)) that numerically approximately corresponded to 10(8) × AP(CaOx) was given the following expression:[Formula: see text]For a series of urine samples with various composition the coefficient of correlation between AP(CaOx)-index(MOUSE) and 10(8) × AP(CaOx) was 0.99 (p = 0.00000). A similar estimate of AP(CaP) (AP(CaP)-index(MOUSE)) was formulated so that it approximately would correspond numerically to 10(14) × AP(CaP) taking the following form:[Formula: see text]For a series of variations in urine composition the coefficient of correlation was 0.95 (p = 0.00000). The two approximate estimates shown in this article are simplified expressions of AP(CaOx) and AP(CaP). The intention of these theoretical calculations was not to get methods for accurate information on the saturation levels in urine, but to have mathematical tools useful for rough conclusions on the outcome of different experimental situations in mice. It needs to be emphasized that the accuracy will be negatively influenced if urine variables not included in the formulas differ very much from basic concentrations.


[Development of mobile MRI system].
This paper describes the development of mobile MRI system. The system technical solution, some calculation and test results are introduced, the technical characteristics are analysed, the same performance has been realized with an MRI system equipped in a vehicle, the market of original fixed MRI system has been extended.


A kinetic study of a ternary cycle between adenine nucleotides.
In the present paper, a kinetic study is made of the behavior of a moiety-conserved ternary cycle between the adenine nucleotides. The system contains the enzymes S-acetyl coenzyme A synthetase, adenylate kinase and pyruvate kinase, and converts ATP into AMP, then into ADP and finally back to ATP. L-Lactate dehydrogenase is added to the system to enable continuous monitoring of the progress of the reaction. The cycle cannot work when the only recycling substrate in the reaction medium is AMP. A mathematical model is proposed whose kinetic behavior has been analyzed both numerically by integration of the nonlinear differential equations describing the kinetics of the reactions involved, and analytically under steady-state conditions, with good agreement with the experimental results being obtained. The data obtained showed that there is a threshold value of the S-acetyl coenzyme A synthetase/adenylate kinase ratio, above which the cycle stops because all the recycling substrate has been accumulated as AMP, never reaching the steady state. In addition, the concept of adenylate energy charge has been applied to the system, obtaining the enabled values of the rate constants for a fixed adenylate energy charge value and vice versa.


Growth, keratinolytic proteinase activity and thermotolerance of dermatophytes associated with alopecia in Uyo, Nigeria.
Mycological research was conducted on the mycelial growth, keratinolytic proteinase activity and thermotolerance ofdermatophytes associated with alopecia patients in Uyo, Nigeria. The results revealed that Microsporum sp. - AP1, Epidermophyton sp. - AP2, Trichophyton rubrum - AP4, Trichophyton mentagrophytes - AP5 and a yeast Candida albicans - AP3 isolated exhibited variable growth and keratinase activity at different temperatures. Microsporum sp. - AP1 and T. mentagrophytes - AP5 survived heat treatment at 90 degrees C but exhibited best mycelial growth at 30 degrees C (with 53.41 mg/50 ml biomass dry weight) and 40 degrees C (with 61.32 mg/50 ml biomass dry weight) respectively, after incubation for 2 weeks. Trichophyton rubrum - AP4 and Epidermophyton sp. - AP2 could not survive heat treatment at 90 degrees C but grew better at 40 degrees C (with 38.52 mg/50 ml biomass dry weight) and 30 degrees C (with 48.32 mg/50 ml biomass dry weight) respectively, over the same incubation period, while C. albicans - AP3 grew better at 30 degrees C with 38.7 mg/50 ml biomass dry weight after 2 weeks, but failed to survive at 70 degrees C. All the isolates except Candida albicans - AP3 survived at 80 degrees C and exhibited great potential to elaborate keratinolytic enzymes, with T. mentagrophytes demonstrating the best potential at 30 degrees C and 40 degrees C. Higher temperatures tended to reduce keratinolytic activities and there were significant (P < 0.05) relationships between biomass weight and enzyme productivities of all the isolates except T. mentagrophytes. This indicates that in some dermatophytes keratinolytic proteinase activity is not a function of cell multiplicity. This plus the high thermostability of the enzymes are important attributes in the consideration of preventive and therapeutic methods against dermatophytes in the tropics.


Dental movement acceleration: Literature review by an alternative scientific evidence method.
The aim of this study was to analyze the majority of publications using effective methods to speed up orthodontic treatment and determine which publications carry high evidence-based value. The literature published in Pubmed from 1984 to 2013 was reviewed, in addition to well-known reports that were not classified under this database. To facilitate evidence-based decision making, guidelines such as the Consolidation Standards of Reporting Trials, Preferred Reporting items for systematic Reviews and Meta-analyses, and Transparent Reporting of Evaluations with Non-randomized Designs check list were used. The studies were initially divided into three groups: local application of cell mediators, physical stimuli, and techniques that took advantage of the regional acceleration phenomena. The articles were classified according to their level of evidence using an alternative method for orthodontic scientific article classification. 1a: Systematic Reviews (SR) of randomized clinical trials (RCTs), 1b: Individual RCT, 2a: SR of cohort studies, 2b: Individual cohort study, controlled clinical trials and low quality RCT, 3a: SR of case-control studies, 3b: Individual case-control study, low quality cohort study and short time following split mouth designs. 4: Case-series, low quality case-control study and non-systematic review, and 5: Expert opinion. The highest level of evidence for each group was: (1) local application of cell mediators: the highest level of evidence corresponds to a 3B level in Prostaglandins and Vitamin D; (2) physical stimuli: vibratory forces and low level laser irradiation have evidence level 2b, Electrical current is classified as 3b evidence-based level, Pulsed Electromagnetic Field is placed on the 4(th) level on the evidence scale; and (3) regional acceleration phenomena related techniques: for corticotomy the majority of the reports belong to level 4. Piezocision, dentoalveolar distraction, alveocentesis, monocortical tooth dislocation and ligament distraction technique, only had case series or single report cases (4(th) level of evidence). Surgery first and periodontal distraction have 1 study at level 2b and corticision one report at level 5. Multiple orthodontic acceleration reports on humans were identified by an alternative evidence level scale, which is a simple and accurate way of determining which techniques are better and have a higher rate of effectiveness. The highest level of evidence for a specific procedure to accelerate orthodontic dental movement up to October 2013 was surgery first followed by low level laser application, corticotomy and periodontal distraction located on level 2, recommendation grade b from this proposed scientific evidence-based scale.


Hospital volume and inpatient mortality after cancer-related gastrointestinal resections: the experience of an Asian country.
Using 4-year nationwide population-based data for Taiwan, this study compared in-hospital surgical mortality rates with hospital volume for five cancer-related gastrointestinal resections. The study sample was drawn from the Taiwan National Health Insurance Research Database. A total of 34,715 patients, each of whom had undergone a cancer-related colectomy, gastrectomy, esophagectomy, pancreatic resection, or liver lobectomy between 2000 and 2003, were selected as the study sample. The outcome measure was in-hospital mortality. The study sample was categorized into five patient groups for each procedure, and logistic regression analyses were performed for each procedure after adjustment for hospital and patient characteristics to assess the independent association between hospital volume and in-hospital mortality. The adjusted odds ratios showed a steady decline in mortality rates for colectomy, gastrectomy, esophagectomy, and liver lobectomy with increasing hospital volume. The adjusted mortality odds for these four procedures in very-high-volume hospitals, relative to very-low-volume hospitals, ranged from .65 to .05. As regards pancreatic resection, after adjustment for patient, clinical, and hospital factors, no statistically significant association was discernible between hospital volume and the likelihood of mortality. After adjustment for hospital and physician characteristics, in four of the five procedures, patients treated at higher-volume hospitals had lower in-hospital mortality rates than those treated at lower-volume hospitals. Our findings confirm, for the most part, the hypothesis that better outcomes are associated with higher-volume hospitals.


Adaptive and phylogenetic influences on musculoskeletal design in cercopithecine primates.
Broad allometric studies of the musculoskeletal system have frequently sought to explain how locomotor variables have been influenced by body mass. To examine animals that vary widely in body mass, these studies have included taxa that differ in their locomotor adaptations and phylogenetic relatedness. Because these sources of diversity could obscure the effects of body mass, this study was designed to test the effects of adaptive differences in limb proportions and phylogeny, as well as body mass, on locomotor kinematics and extensor muscle mechanical advantage. More specifically, two hypotheses were tested in a sample of closely related animals: (i) that, among animals with similar body mass, those with longer limb segments should adopt more extended limb postures to moderate the joint and midshaft bending moments that they experience, and (ii) that body mass will have similar influences on joint posture and joint moments in closely related and diverse mammalian samples. Three-dimensional kinematic and synchronous force-platform data were collected for six individual cercopithecine monkeys ranging in mass from 4kg to 24kg and at a range of walking speeds. Comparisons among three monkeys with similar body mass but different limb segment lengths reveal a significant effect of limb proportion on posture. That is, animals with longer limbs frequently use more extended limb postures and can have correspondingly lower joint moments. The scaling of locomotor variables across the entire sample of closely related monkeys was generally similar to published results for a diverse sample of mammals, with larger monkeys having more extended limb postures, lower joint moments and greater effective mechanical advantage (EMA) for their limb extensor musculature. Ankle EMA, however, did not increase with body mass in the primate sample, suggesting that clade-specific adaptive differences (e.g. the use of arboreal supports by primates) may constrain the effects of body mass.


Age structure of the population in Belgium and social security.
The effects of demographic aging and of various socioeconomic factors on the social security system in Belgium are explored. "Special attention is given to the impact of the ageing of the population on the pension problem. Based on a simple formula a series of percentages of taxation have been calculated as a function of shifts in the proportion of retired vs. active population and in the proportion of the average income vs. the average amount of pension. One of the conclusions is that the progressive ageing of the population will become the most significant factor in the growth of social expenditures."


[Ultrasound diagnosis of the transplanted kidney].
Ultrasound is the primary imaging modality after kidney transplantation. Its general availability and the absence of radiation exposure and discomfort for the patient also make it a suitable procedure for follow-up. Simple B-mode sonography provides comprehensive information on the morphology of the renal transplant and surrounding structures, while color-coded duplex sonography (CCDS) additionally allows assessment of the anastomoses and organ perfusion. More recent technical advances such as power Doppler ultrasound appear to improve in particular the assessment of peripheral circulation. The possibilities and limitations of the various sonographic techniques in the evaluation of kidney transplants are discussed with special reference to the most important clinical aspects and some basic technical concepts.


Patently controversial: markets, morals, and the President's proposal for embryonic stem cell research.
This essay considers the implications of President George W. Bush's proposal for human embryonic stem cell research. Through the perspective of patent law, privacy, and informed consent, we elucidate the ongoing controversy about the moral standing of human embryonic stem cells and their derivatives and consider how the inconsistencies in the president's proposal will affect clinical practice and research.


Evaluation of the antioxidative and genotoxic effects of sodium butyrate on breast cancer cells.
Oncogenic stimulation shows a rise in reactive oxygen species (ROS), and ROS can eventually induce carcinogenesis by causing DNA damage. In this context, this study aims to evaluate some biochemical and genotoxic changes in the control of cell death caused by NaBu (Sodium butyrate). treatment in breast cancer cells. NaBu's impact on cell proliferation was determined via WST-1 assay. The lipid peroxidation (MDA), reduced glutathione (GSH), Nitric Oxide (NO), hydrogen peroxide (H2O2), and superoxide dismutase (SOD) enzyme levels were determined biochemically. NaBu-induced genotoxic damage was estimated via single-cell gel electrophoresis (SCGE). NaBu reduced cell viability and potentially induced GSH, but decreased SOD enzyme activity and the level of MDA and NO decreased also H2O2 decreased at different times and NaBu concentrations. Higher NaBu concentrations amplified DNA damage in MCF-7 cells compared to the control group. NaBu shows anticancer and genotoxic effects, especially through antioxidant enzymes, one of the oxidative stress parameters in breast cancer. However, the anticancer and genotoxic effects of NaBu is changed in the oxidative stress parameters with time and treatment concentration of NaBu in MCF-7 cells. Furthermore, his oxidative stress-dependent effect changes need to be clarified by further evaluation with molecular and more biochemical parameters.


Dietary Arginine Regulates Severity of Experimental Colitis and Affects the Colonic Microbiome.
There is great interest in safe and effective alternative therapies that could benefit patients with inflammatory bowel diseases (IBD). L-arginine (Arg) is a semi-essential amino acid with a variety of physiological effects. In this context, our aim was to investigate the role of dietary Arg in experimental colitis. We used two models of colitis in C57BL/6 mice, the dextran sulfate sodium (DSS) model of injury and repair, and Citrobacter rodentium infection. Animals were given diets containing (1) no Arg (Arg0), 6.4 g/kg (ArgNL), or 24.6 g/kg Arg (ArgHIGH); or (2) the amino acids downstream of Arg: 28 g/kg L-ornithine (OrnHIGH) or 72 g/kg L-proline (ProHIGH). Mice with DSS colitis receiving the ArgHIGH diet had increased levels of Arg, Orn, and Pro in the colon and improved body weight loss, colon length shortening, and histological injury compared to ArgNL and Arg0 diets. Histology was improved in the ArgNL vs. Arg0 group. OrnHIGH or ProHIGH diets did not provide protection. Reduction in colitis with ArgHIGH diet also occurred in C. rodentium-infected mice. Diversity of the intestinal microbiota was significantly enhanced in mice on the ArgHIGH diet compared to the ArgNL or Arg0 diets, with increased abundance of Bacteroidetes and decreased Verrucomicrobia. In conclusion, dietary supplementation of Arg is protective in colitis models. This may occur by restoring overall microbial diversity and Bacteroidetes prevalence. Our data provide a rationale for Arg as an adjunctive therapy in IBD.


Psychotropic drugs in Bulgaria-frequency and risk of adverse drug reactions.
The aim of the study is to determine the frequency and risk of appearance of adverse drug reactions/ADRs/during the treatment with psychotropic drugs. The first part of the study is an analysis of the use of the psychotropic drugs for one-year period of time in our country, performed by DDD methodology. An attempt is made to equalize the Bulgarian list of the psychotropic drugs with the ATC classification and to estimate the DDD/1000/day. The data for Bulgaria is compared with that of the other countries. The collected data for the psychotropic drug use is divided into 2 groups: Psycholeptics and Psychoanaleptics. It is made an attempt to explain the main differences between them. The number of the standard therapeutic courses/NT/is used for assessment of the frequency and risk of ADRs. The results from the study show that the determined frequency of appearance of ADR for the different drugs is within "rare" and "very rare' for 100,000 inhabitants, according to the WHO terminology. Only for the drug Tardyl (EGIS Pharmaceuticals, Hungary) with INN Aminobarbitalum + Glutethimidum + Promethazini hydrochloridum the frequency is above 1%. That fact makes us to recommend a limitation of the prescription and usage of this drug to the Bulgarian Ministry of Health and to the National Drug Agency.


Getting accredited for population health.
The inclusion of population health in the accreditation process is an important new direction in the Canadian healthcare system. While quality improvement is a concept familiar to most clinicians and administrators, the inclusion of population health may raise some questions: What is "population health?"; Should healthcare organizations be responsible for population health?; If so, what could they and should they be doing about it?; How would a healthcare organization achieve accreditation in population health?


Prenylation of HDAg and antiviral drug development.
Hepatitis delta virus (HDV) is an important cause of acute and chronic liver disease. Current medical therapies are unable to effectively eradicate HDV infections. Research into the molecular virology of the HDV life cycle has revealed a fascinating collection of biology. These insights are now beginning to be translated into new potential treatment strategies. For example, an essential step in the virus assembly process involves the post-translational lipid modification of a specific HDV protein, namely prenylation of large delta antigen. Preventing prenylation abolishes virus particle formation. Drugs capable of specifically inhibiting prenylation have been developed for use in humans. These agents represent a new class of antiviral agents, with HDV as a first target. Here, a brief review of the HDV life cycle emphasizing the role of prenylation is presented along with implications for drug development and therapy.


Lichen planus confined to a radiation therapy site.
We report the case of a 58-year-old man with lichen planus localized to a radiation site. To our knowledge, this is the first reported case of radiation-induced lichen planus in the English-language literature.


Urinary tract infection in postmenopausal women.
Urinary tract infection (UTI) is the most common bacterial infection in women in general and in postmenopausal women in particular. Two groups of elderly women with recurrent UTI should be differentiated regarding age and general status: healthy, young postmenopausal women aged 50 to 70 years who are neither institutionalized or catheterized and elderly institutionalized women with or without a catheter. Bacteriuria occurs more often in elderly functionally impaired women, but in general it is asymptomatic. However, the risk factors associated with recurrent UTI in elderly women are not widely described. In a multivariate analysis it was found that urinary incontinence, a history of UTI before menopause, and nonsecretor status were strongly associated with recurrent UTI in young postmenopausal women. Another study described the incidence and risk factors of acute cystitis among nondiabetic and diabetic postmenopausal women. Independent predictors of infection included insulin-treated patients and a lifetime history of urinary infection. Borderline associations included a history of vaginal estrogen cream use in the past month, kidney stones, and asymptomatic bacteriuria at baseline. Another important factor in postmenopausal women is the potential role that estrogen deficiency plays in the development of bacteriuria. There are at least two studies showing a beneficial effect of estrogen in the management of recurrent bacteriuria in elderly women. One of these studies showed that vaginal estrogen cream reduced vaginal pH from 5.5±0.7 to 3.6±1.0, restored lactobacillus, and decreased new episodes of UTI. Another study reported similar results using an estriol vaginal ring. However, contradictory results are found in the literature. For example, additional studies found that the use of estriol-containing vaginal pessaries was less effective than oral nitrofurantoin macrocrystals in preventing UTI in postmenopausal women. Two other studies also did not find any benefit in the reduction of UTI by oral estrogen therapy. Unfortunately, the use of estrogen in preventing UTI in postmenopausal women remains questionable. New strategies have been researched for reducing the use of antibiotics in the prevention and treatment of UTI. Two of them are probiotics and cranberry juice or capsules. Although several studies regarding probiotics and cranberry juice or capsules have reported a reduction of episodes of UTI, there is no conclusive evidence that they are useful in the prevention of UTI in postmenopausal women. As for the optimal drug, dosage, and length of treatment for UTI in the elderly, there are no studies comparing these data with the treatment for young women.


Prevalence of familial hyperhomocyst(e)inemia in men with premature coronary artery disease.
Elevated plasma levels of homocyst(e)ine have been reported to be more prevalent in patients with coronary artery disease (CAD) than in controls. The purpose of this study was to determine whether this elevation was genetic. We determined homocyst(e)ine levels in 176 men with premature CAD (greater than 50% stenosis of a major epicardial coronary artery occurring before the age of 60 years) and in 255 controls free of cardiovascular disease. Homocyst(e)ine levels were higher in the CAD group compared with controls (13.9 +/- 6.7 versus 10.9 +/- 4.9 nmol/ml, p less than 0.001); in addition, 28% of CAD patients had homocyst(e)ine levels above the 90th percentile of controls. Statistical analysis revealed that homocyst(e)ine levels were not related to the presence of hypertension or diabetes, smoking, or plasma levels of lipoprotein cholesterol and apolipoproteins A-I and B. The families of 71 CAD patients were sampled (selected on the basis of availability of relatives) and included 60 spouses and 239 first-degree relatives; 370 subjects were thus sampled. Spearman correlations between probands and spouses (r = 0.264, p = 0.041) and between mean values for parent and offspring (r = 0.356, p = 0.002) for homocyst(e)ine levels indicated that homocyst(e)ine levels are in part genetically determined. In 20 families (28.2%), the proband had homocyst(e)ine levels greater than the 90th percentile; familial segregation was observed in 10 of these kindreds. Therefore, 14% of CAD patients had familial hyperhomocyst(e)inemia. In conclusion, our data suggest that plasma homocyst(e)ine is a risk factor for the development of CAD, independent of other cardiovascular risk factors, and that this elevation is in part genetically determined.


Clinical impact of monocyte distribution width and neutrophil-to-lymphocyte ratio for distinguishing COVID-19 and influenza from other upper respiratory tract infections: A pilot study.
The coronavirus disease 2019 (COVID-19) has become a pandemic. Rapidly distinguishing COVID-19 from other respiratory infections is a challenge for first-line health care providers. This retrospective study was conducted at the Taipei Medical University Hospital, Taiwan. Patients who visited the outdoor epidemic prevention screening station for respiratory infection from February 19 to April 30, 2020, were evaluated for blood biomarkers to distinguish COVID-19 from other respiratory infections. Monocyte distribution width (MDW) ≥ 20 (odds ratio [OR]: 8.39, p = 0.0110, area under curve [AUC]: 0.703) and neutrophil-to-lymphocyte ratio (NLR) < 3.2 (OR: 4.23, p = 0.0494, AUC: 0.673) could independently distinguish COVID-19 from common upper respiratory tract infections (URIs). Combining MDW ≥ 20 and NLR < 3.2 was more efficient in identifying COVID-19 (AUC: 0.840). Moreover, MDW ≥ 20 and NLR > 5 effectively identified influenza infection (AUC: 0.7055). Thus, MDW and NLR can distinguish COVID-19 from influenza and URIs.


Increased expression of protein kinase C beta activates ERK3.
In a prior study, we have shown that stable transfection of expression plasmids for protein kinases C beta 1 (PKC beta 1) or PKC beta 2 into differentiated colon cancer cells led to elevated levels of PKC beta 1 or PKC beta 2 protein and PKC beta kinase activities in the transfectants, without altering PKC alpha levels. PKC gamma is not found in these cells, so the major modulation was in PKC beta. PKC beta transfectant cells exhibited blocked differentiation, increased growth rate in athymic mice, and restoration of the basic fibroblast growth factor response pathway. In this study, we have extended the analysis of these PKC beta transfectants to the mitogen-activated protein kinase ERK3. Analysis of cell lysates on the mitogen-activated protein kinase substrate myelin basic protein by in gel kinase assay showed increased activity at 63 kDa, the size of ERK3, in each of two PKC beta 1 and each of two PKC beta 2 transfectants compared with the vector control transfectant. ERK3 was expressed at equal abundance in PKC beta 1, PKC beta 2, and control transfectant cells as demonstrated by Western blotting and by immunoprecipitation with anti-ERK3 monoclonal antibody. However, a > 10-fold increase in ERK3 activity in each PKC beta transfectant was shown by immunoprecipitation with anti-ERK3 monoclonal antibody followed by either immune complex kinase assay or by in gel kinase assay. Thus, while overexpression of transfected PKC beta does not lead to overexpression of ERK3, it does lead to constitutive activation of ERK3. A causal link between PKC beta overexpression and ERK3 activation was established because 12-O-tetradecanoylphorbol-13-acetate treatment down-regulated both PKC and ERK3 activities in both PKC beta 1 transfectants. ERK3 activity was found in nuclear and membrane fractions in each PKC beta transfectant, in contrast to controls, perhaps accounting for constitutive activation of ERK3 in cells with elevated levels of PKC beta 1 or PKC beta 2.


Addressing algal blooms by bio-pumps to reduce greenhouse gas production and emissions with multi-path.
The collapse of dense algal blooms is identified as a significant source of methane (CH4) emissions. When flocculation is used for algae removal, algal carbon is often turned into CH4 and carbon dioxide (CO2). Here, we established a "bio-pump" to control algal blooms and reduce greenhouse gas (GHG) emissions by the introduction of submerged macrophytes to the aquatic ecosystem and combination of flocculation and capping. The results suggested that this strategy contributed to an approximately 98% algae removal and sustainably improved dissolved oxygen (DO) in the water and sediment after the 40-day incubation. The aerobic condition at the sediment-water interface and deeper oxygen penetration in the sediment inhibited the abundance of microorganisms related to anaerobic CH4 production, then changed the metabolic pathway and fate of algal carbon. After the 40-day incubation, compared with flocculation-capping treatments, the bio-pump reduced 69.07% CH4 and 77.57% CO2 emissions, which was jointly contributed by the inhibition of anaerobic CH4 production, aerobic oxidation of CH4 and carbon sequestration of submerged macrophytes. This was also demonstrated from the finding of a decrease in methyl coenzyme M reductase (mcrA) gene, an increase in particulate methane monooxygenase (pmoA) gene and the absorption of 13C-labeled from algae biomass by submerged macrophytes at the end of incubation. Therefore, the bio-pump established in the present study can improve DO in algal blooms water and turn algal-derived organic matter into the plant biomass, which supplied a sustainable method for algae removal and GHG reduction.


Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer.
Intracellular recordings were obtained from horizontal and bipolar cells of the superfused, isolated retina-eyecup of the rabbit. The putative neurotransmitters aspartate, glutamate, and several analogues were added to the superfusate while the membrane potential and light-responsiveness of the retinal neurons were monitored. Both L-aspartate and L-glutamate mimicked the actions of the endogenous photoreceptor transmitter on horizontal cells, on-bipolar cells, and off-bipolar cells. At applied concentrations of 2.5-20 mM, the actions of L-aspartate and L-glutamate were indistinguishable. D-aspartate potentiated the effects of both L-aspartate and L-glutamate on horizontal cells. This suggests that active uptake systems for these amino acids exist in the outer plexiform layer (OPL) of the rabbit retina. The glutamate analogue kainate produced effects similar to those of aspartate and glutamate on second-order neurons, but at concentrations lower by over two orders of magnitude. The glutamate analogue quisqualate had effects similar to kainate but with much less potency. The aspartate analogue n-methyl DL-aspartate (NMDLA) antagonized the effects of the photoreceptor transmitter on horizontal and off-bipolar cells. This action of NMDLA was only observed at low concentrations (50 microM). In addition, NMDLA could block the effects of exogenously applied kainate. The NMDLA had no clear effects on on-bipolar cells. The glutamate analogue 2-amino-4-phosphonobutyrate reversibly blocked the responses of on-bipolar cells but had no effect on either horizontal or off-bipolar cell responses. This suggests that on-bipolar cells possess a unique synaptic receptor. The aspartate analogue 2-amino-3-phosphonoproprionate did not show this selectivity, suggesting that this unique receptor is a glutamate-preferring receptor. The antagonists alpha-methyl glutamate, alpha-amino adipate, and glutamate diethyl ester all showed only a weak ability to antagonize the actions of the photoreceptor transmitter on second-order neurons. The results of this study indicate that glutamate or a glutamate-like substance is the likely transmitter of rods and cones in the rabbit retina. A comparison of the present findings with those previously obtained in lower vertebrate retinas suggests that the basic pharmacological design of the OPL of all vertebrate retinas is very similar.


On the development of the chondrocranium and the histological anatomy of the head in perinatal stages of marsupial mammals.
An overview of the literature on the chondrocranium of marsupial mammals reveals a relative conservatism in shape and structures. We document the histological cranial anatomy of individuals representing Monodelphis domestica, Dromiciops gliroides, Perameles sp. and Macropus eugenii. The marsupial chondrocranium is generally characterized by the great breadth of the lamina basalis, absence of pila metoptica and large otic capsules. Its most anterior portion (cupula nasi anterior) is robust, and anterior to it there are well-developed tactile sensory structures, functionally important in the neonate. Investigations of ossification centers at and around the nasal septum are needed to trace the presence of certain bones (e.g., mesethmoid, parasphenoid) across marsupial taxa. In many adult marsupials, the tympanic floor is formed by at least three bones: alisphenoid (alisphenoid tympanic process), ectotympanic and petrosal (rostral and caudal tympanic processes); the squamosal also contributes in some diprotodontians. The presence of an entotympanic in marsupials has not been convincingly demonstrated. The tubal element surrounding the auditory tube in most marsupials is fibrous connective tissue rather than cartilage; the latter is the case in most placentals recorded to date. However, we detected fibrocartilage in a late juvenile of Dromiciops, and a similar tissue has been reported for Tarsipes. Contradictory reports on the presence of the tegmen tympani can be found in the literature. We describe a small tegmen tympani in Macropus. Several heterochronic shifts in the timing of development of the chondocranium and associated structures (e.g., nerves, muscles) and in the ossification sequence have been interpreted as largely being influenced by functional requirements related to the altriciality of the newborn marsupial during early postnatal life. Comparative studies of chondocranial development of mammals can benefit from a solid phylogenetic framework, research on non-classical model organisms, and integration with imaging and sectional data derived from computer-tomography.


Missing Race and Ethnicity Data among COVID-19 Cases in Massachusetts.
Infectious disease surveillance frequently lacks complete information on race and ethnicity, making it difficult to identify health inequities. Greater awareness of this issue has occurred due to the COVID-19 pandemic, during which inequities in cases, hospitalizations, and deaths were reported but with evidence of substantial missing demographic details. Although the problem of missing race and ethnicity data in COVID-19 cases has been well documented, neither its spatiotemporal variation nor its particular drivers have been characterized. Using individual-level data on confirmed COVID-19 cases in Massachusetts from March 2020 to February 2021, we show how missing race and ethnicity data: (1) varied over time, appearing to increase sharply during two different periods of rapid case growth; (2) differed substantially between towns, indicating a nonrandom distribution; and (3) was associated significantly with several individual- and town-level characteristics in a mixed-effects regression model, suggesting a combination of personal and infrastructural drivers of missing data that persisted despite state and federal data-collection mandates. We discuss how a variety of factors may contribute to persistent missing data but could potentially be mitigated in future contexts.


Rho GTPases in the Amygdala-A Switch for Fears?
Fear is a fundamental evolutionary process for survival. However, excess or irrational fear hampers normal activity and leads to phobia. The amygdala is the primary brain region associated with fear learning and conditioning. There, Rho GTPases are molecular switches that act as signaling molecules for further downstream processes that modulate, among others, dendritic spine morphogenesis and thereby play a role in fear conditioning. The three main Rho GTPases-RhoA, Rac1, and Cdc42, together with their modulators, are known to be involved in many psychiatric disorders that affect the amygdala's fear conditioning mechanism. Rich2, a RhoGAP mainly for Rac1 and Cdc42, has been studied extensively in such regard. Here, we will discuss these effectors, along with Rich2, as a molecular switch for fears, especially in the amygdala. Understanding the role of Rho GTPases in fear controlling could be beneficial for the development of therapeutic strategies targeting conditions with abnormal fear/anxiety-like behaviors.


Particle-induced cytokine responses in cardiac cell cultures--the effect of particles versus soluble mediators released by particle-exposed lung cells.
Increased levels of particulate matter have been associated with adverse effects in the respiratory as well as the cardiovascular system. The biological mechanisms behind these associations are still unresolved. Among potential mechanisms, particulate matter-associated cardiac effects may be initiated by inhaled small-sized particles, particle components and/or mediators related to inflammation that translocate into the pulmonary circulation. In the present study cytokine responses (interleukin [IL]-6, IL-1beta, and tumor necrosis factor [TNF]-alpha) of primary rat cardiomyocytes and cardiofibroblasts in mono- and cocultures induced by direct exposure to particles, were compared with cytokine responses induced by mediators released by particle-exposed primary rat epithelial lung cells (conditioned media). Cells were exposed to a model ultrafine particle (ultrafine carbon black, Printex 90) and in selected experiments to an urban air particle sample (SRM 1648, St Louis, MO). In lung cell cultures both particle types induced release of IL-6 and IL-1beta, whereas TNF-alpha was only detected upon exposure to St Louis particles. The release of IL-6 by cardiac cells was strongly enhanced upon exposure to conditioned media, and markedly exceeded the response to direct particle exposure. IL-1, but not TNF-alpha, seemed necessary, but not sufficient, for this enhanced IL-6 release. The role of IL-1 was demonstrated by use of an IL-1 receptor antagonist that partially reduced the effect of the conditioned media, and by a stimulating effect on the cardiac cell release of IL-6 by exogenous addition of IL-1alpha and IL-1beta. These in vitro findings lend support to the hypothesis that particle-induced cardiac inflammation and disease may involve lung-derived mediators.


Morphology of the ligaments located on the medial side of the ankle and on the plantar surface of the foot.
To have biodynamic features, the feet have bones located in a special posture, the joints that keep together those bones, the ligaments that provide linkage to those joints, and tendons of muscles particularly which end the foot. This study aimed to research the morphology of the medial side and plantar ligaments. The study was conducted on a total of 30 feet belonging to 2 women and 13 men cadavers that exist at the Anatomy Department of the Medical Faculty of Uludag University. After the dissections, 61 parameters that belonging to the ligaments and general features of the foot, were evaluated. The statistical analysis of the collected data was evaluated by SPSS 20.0. According to the findings, while the descriptive statistics of the foot and the ligaments related to the foot, the statistically significant difference of any of the parameters wasn't observed when they were compared between the right and left sides of the foot. In terms of the correlative relations, the parameters that showed high correlation were chosen and 28 formulas were developed using regression analysis. We foresee that our findings of the features belonging to normal anatomic structures will deepen our knowledge besides providing important benefits before or during orthopedic and plastic surgery operations related to the region. Also, our findings were discussed by comparing the findings of similar studies belonging to many other researchers in literature, and our study's contribution to the literature was evaluated.


Characterizing the Health of Older Rural Australians Attending Rural Events: Implications for Future Health Promotion Opportunities.
This paper describes the health of older Australians (>65 years) attending rural events to inform health promotion interventions for rural populations. This cross-sectional study collected survey data and objective health measures between 2017 and 2020 at two events held in rural New South Wales, Australia. Participants included in the analysis were adults > 65 years of age. Data included demographic and health information, anthropometric measures (height, weight, waist circumference), and dietary and physical activity data. A total of 256 people > 65 years participated. Our sample, which was mostly male (59.0%), contained people aged between 66 and 75 years (72.3%). Participants lived in either a large rural (34.0%) or small rural town (22.3%), with low levels of education (60.9% did not complete high school). Dietary quality was rated as below average. All but 17.2% of the participants reported having a health condition. The risk of a health condition was associated with increasing age, lower education, and higher waist circumference, but not remoteness. Rural events may provide an opportunity to access, engage with, and understand the health of older rural Australians, especially males. They may offer ideal contexts for health and nutrition promotion opportunities in rural areas where access to health professionals is limited.


Molecular Genetic Diversity and Combining Ability for Some Physiological and Agronomic Traits in Rice under Well-Watered and Water-Deficit Conditions.
Water deficit is a pivotal abiotic stress that detrimentally constrains rice growth and production. Thereupon, the development of high-yielding and drought-tolerant rice genotypes is imperative in order to sustain rice production and ensure global food security. The present study aimed to evaluate diverse exotic and local parental rice genotypes and their corresponding cross combinations under water-deficit versus well-watered conditions, determining general and specific combining ability effects, heterosis, and the gene action controlling important traits through half-diallel analysis. In addition, the research aimed to assess parental genetic distance (GD) employing simple sequence repeat (SSR) markers, and to determine its association with hybrid performance, heterosis, and specific combining ability (SCA) effects. Six diverse rice genotypes (exotic and local) and their 15 F1 hybrids were assessed for two years under water-deficit and well-watered conditions. The results revealed that water-deficit stress substantially declined days to heading, plant height, chlorophyll content, relative water content, grain yield, and yield attributes. Contrarily, leaf rolling and the sterility percentage were considerably increased compared to well-watered conditions. Genotypes differed significantly for all the studied characteristics under water-deficit and well-watered conditions. Both additive and non-additive gene actions were involved in governing the inheritance of all the studied traits; however, additive gene action was predominant for most traits. The parental genotypes P1 and P2 were identified as excellent combiners for earliness and the breeding of short stature genotypes. Moreover, P3, P4, and P6 were identified as excellent combiners to increase grain yield and its attributes under water-deficit conditions. The hybrid combinations; P1 × P4, P2 × P5, P3 × P4, and P4 × P6 were found to be good specific combiners for grain yield and its contributed traits under water-deficit conditions. The parental genetic distance (GD) ranged from 0.38 to 0.89, with an average of 0.70. It showed lower association with hybrid performance, heterosis, and combining ability effects for all the studied traits. Nevertheless, SCA revealed a significant association with hybrid performance and heterosis, which suggests that SCA is a good predictor for hybrid performance and heterosis under water-deficit conditions. Strong positive relationships were identified between grain yield and each of relative water content, chlorophyll content, number of panicles/plant, number of filled grains/panicle, and 1000-grain weight. This suggests that these traits could be exploited as important indirect selection criteria for improving rice grain yield under water-deficit conditions.


Computers a cornerstone of evidence-based care, conference told.
Computers are poised to become key players in the delivery of health care, but are physicians ready for them? A recent conference on medical communication in the electronic era examined the potential of computers to assist in diagnosis, provide continuing medical education, disseminate evidence and research findings, and simplify practice management. However, delegates were told that even though many medical practices are computerized, it is often staff members and not physicians who use the technology. For computers to gain wider acceptance for medical purposes, physicians need to be made comfortable with their use at an early stage of training.


Effects of Heat Shock on Growth and on Lipid and beta-Glucan Synthetases in Leaves of Phaseolus vulgaris and Vigna sinensis.
Primary leaves of intact plants of Phaseolus vulgaris and Vigna sinensis 7 to 9 days old were dipped in water for 2 minutes at 47.4 +/- 0.2 C and 48.7 +/- 0.5 C, respectively. Leaf growth was inhibited within the first 20 hours, and growth partially or completely recovered in a subsequent 20-hour period. Analysis of the glucolipid and beta-1, 3- and beta-1, 4-glucan synthetases showed that the most evident effects of heat shock were the severe inhibition of the synthesis of beta-1, 4-glucosyl glycosidic linkages and stimulation of beta-1, 3-linkage synthesis. The stimulation appeared either immediately after treatment or within the first 20 hours and lasted at least 60 hours after treatment. Phaseolus plants reacted more intensely to the heat shock, reflecting a possible genetic difference in the response mechanisms.


Risk factors of vitamin K antagonist overcoagulation.
The aims of this prospective study were to identify, in vitamin K antagonist (VKA)-treated patients, factors associated with INR values: (i) greater than 6.0. and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We also assessed VKA-related morbidity in these patients. During a 6-month period, 3090 consecutive patients were referred to our Department of Internal Medicine, including 412 VKA-treated patients. At admission, the medical records of VKA-treated patients were reviewed for type, duration and indication of VKA therapy, previous medical history of VKA-related hemorrhage, comorbidities and concomitant medications. Forty of the 412 VKA-treated patients (9.7%) exhibited oral anticoagulant related overcoagulation. VKA overcoagulation was associated with high morbidity, leading to major bleeding in 27.5% of cases; moreover, 12.5% of these patients died, death being mainly due to major bleeding. Under multivariate analysis, significant factors for VKA-related overcoagulation were as follows: previous medical history of VKA therapy-related hemorrhage (P=0.00001) and INR levels over therapeutic range (P=0.0006), chronic liver disease (P=0.03), therapy with amiodarone (P=0.009); in contrast, statin therapy was found to be a protective factor of VKA overcoagulation (P=0.008). The knowledge of predictive factors of VKA-related overcoagulation seems of utmost importance to improve patients' management. Our study underlines the fact that the potential of drug interaction should be taken into account when choosing amiodarone for patients receiving VKAs. Interestingly, long-term (>6 month) statin therapy may be a protective factor of VKA overcoagulation. Our findings, therefore, suggest that there may be no need to switch long-term users of VKA and statin to a safer alternative therapy.


Extruded linseed and rapeseed both influenced fatty acid composition of total lipids and their polar and neutral fractions in longissimus thoracis and semitendinosus muscles of finishing Normand cows.
The effects of extruded linseed and rapeseed on lipids and FA composition of total, polar and neutral lipids of longissimus thoracis (LT) and semitendinosus (ST) muscles were investigated in 21 Normand cull cows. Animals were assigned in a 100 d finishing period to straw (30%) and concentrate (70%) based (C) or the same diet supplemented with linseed (L) or with rapeseed (66%) plus linseed (33%) (RL). Beef polar and neutral lipids were purified by liquid chromatography and their FA analysed by GLC. Trans and cis 18:1, purified by HPLC from total FA methyl esters, were analysed by GLC-MS. L and LR diets did not increase beef lipid deposition, but had modified FA composition of both LT and ST muscles in favouring deposition of 18:3n-3 and 9cis,11tr 18:2 (CLA), mainly to the detriment of 18:1∆9 cis (neutral lipids) and 18:2n-6 (polar lipids). However, they did not favour deposition of LC n-3 PUFA in the two muscles, but had increased deposition of trans 18:1 significantly, especially of ∆13tr to ∆16tr isoforms to the detriment of ∆10tr 18:1 (L diet) and of ∆11tr 18:1 (RL diet).


Effect of endogenously synthesized and exogenously applied ethanol on tomato fruit ripening.
Tomato (Lycopersicon esculentum Mill. var Castlemart) fruit ripening was inhibited by tissue concentrations of ethanol that were produced by either exposure to exogenous ethanol vapors or synthesis under anaerobic atmospheres. Ethanol was not detected in aerobically ripened tomato fruit. Ripening was not inhibited by exposure to methanol at an equivalent molar concentration to inhibitory concentrations of ethanol, while ripening was slightly more inhibited by n-propanol than by equivalent molar concentrations of ethanol. The mottled appearance of a few ripened ethanol-treated fruit was not observed in n-propanol-treated fruit.


Circulatory and metabolic effects of hypoxia in the hyperinsulinemic ovine fetus.
Fetuses of women whose diabetes is poorly controlled often exhibit hypoxemia and elevated catecholamine concentrations at birth. In the ovine fetus, experimental hyperinsulinemia results in hypoxemia, elevated catecholamine concentrations, and hemodynamic changes. Limited oxygen availability occurring during pregnancy-related complications and/or delivery may present an additional risk to the hyperinsulinemic fetus. In this study, we tested the hypothesis that hypoxia induced via acutely limiting oxygen availability compromises the hemodynamically and metabolically stressed but compensated hyperinsulinemic ovine fetus. Fetuses receiving insulin (n = 8) or placebo (n = 5) for 48 h were exposed to maternally induced hypoxia. Hypoxic hypoxia was associated with a surge in catecholamines in the hyperinsulinemic fetuses. During hypoxia, this group exhibited insulin-related sustained increases in the combined ventricular output and fetal body blood flow, accentuation of the prior insulin-related increase in blood flow to the heart, decreased systemic oxygen delivery, accentuation of the insulin-related increased oxygen extraction, reductions in the insulin-related increased systemic oxygen uptake, sustained increases in regional oxygen delivery to the heart and adrenal glands, reductions in the insulin-related increased delivery to the carcass, and decreased oxygen delivery to the kidneys and gastrointestinal tract. We conclude that, in the hyperinsulinemic ovine fetus, hypoxic hypoxia attenuates the hyperinsulinemia-mediated increased systemic oxygen uptake. Regional oxygen transport is preserved to vital regions (brain, heart, and adrenal glands) by increased perfusion and compromised to certain other regions (kidneys and gastrointestinal tract), because the increases in perfusion are insufficient to offset the limited oxygen availability.


[Abnormal glucose regulation and the risk factors in middle-aged and elderly residents from Baoding City].
To assess the prevalence of type 2 diabetes mellitus (T2DM) and impared glucose regulation(IGR) in the residents of Baoding City, including 1-impaired fasting glucose(1-IFG), 1-impaired glucose tolerance (1-IGT) and IFG/IGT, to identify the main risk factors of abnormal glucose regulation. A sample of 3212 community residents aged over 40 years old was selected from three communities of Baoding City by random cluster sampling. The survey was conducted by trained investigators using a standardized questionnaire. The subjects received physical examination and laboratory test, such as SBP, SDP, TC, TG, LDL-C, HDL-C, FBG, 2h PG, WHR and BMI. The data were analyzed by Accumulative Logistic Regression. The standardized prevalence of T2DM, -IFG, 1-IGT and IFG/IGT was 19.03%, 1.42%, 5.92% and 1.34%, and 27.72% of residents over 40 yeas old in Baoding City threatened by the trouble of abnormal glucose regulation. The results demonstrated that the gender, age, occupation, fruit intake, temper or disposition, BMI, WC, WHR, SBP, TG, DM family history and the history of fetal macrosomia (female only) were significantly associated with the abnormal glucose regulation, but taking more fruits and the female sex were protective factors. Cardio-cerebrovascular disease was the highest among the complications prevalent in diabetic patients, more than one complication is common, and the detection rate of new diabetic patients was 8.19%. The prevalence of T2DM is high in the residents of Baoding City, which is influenced by many factors.


Stabilization of Sn Anode through Structural Reconstruction of a Cu-Sn Intermetallic Coating Layer.
The metallic tin (Sn) anode is a promising candidate for next-generation lithium-ion batteries (LIBs) due to its high theoretical capacity and electrical conductivity. However, Sn suffers from severe mechanical degradation caused by large volume changes during lithiation/delithiation, which leads to a rapid capacity decay for LIBs application. Herein, a Cu-Sn (e.g., Cu3 Sn) intermetallic coating layer (ICL) is rationally designed to stabilize Sn through a structural reconstruction mechanism. The low activity of the Cu-Sn ICL against lithiation/delithiation enables the gradual separation of the metallic Cu phase from the Cu-Sn ICL, which provides a regulatable and appropriate distribution of Cu to buffer volume change of Sn anode. Concurrently, the homogeneous distribution of the separated Sn together with Cu promotes uniform lithiation/delithiation, mitigating the internal stress. In addition, the residual rigid Cu-Sn intermetallic shows terrific mechanical integrity that resists the plastic deformation during the lithiation/delithiation. As a result, the Sn anode enhanced by the Cu-Sn ICL shows a significant improvement in cycling stability with a dramatically reduced capacity decay rate of 0.03% per cycle for 1000 cycles. The structural reconstruction mechanism in this work shines a light on new materials and structural design that can stabilize high-performance and high-volume-change electrodes for rechargeable batteries and beyond.


Four new diterpenoids isolated from the Euphorbia rapulum.
Four new diterpenoids named 1-epi-9-hydroxydepressin (1), 1-epi-8-hydroxydepressin (2), 2,13,9-trihydroxy-labda-8(17),12(E),14-triene (3) and tagalsin I (4) were isolated from Euphorbia rapulum. The structures of these compounds were elucidated by means of various spectroscopic methods. All the isolated compounds were evaluated for cytotoxic activities against HepG2, MCF-7, and C6 cell lines, and compound 4 showed moderate selective activity against MCF-7 cell line with an IC50 value of 31.8 μM.


Detection of IgG, IgM and IgA antibodies in patients with uncomplicated Chlamydia trachomatis infection: a comparison between enzyme linked immunofluorescent assay and isolation in cell culture.
The diagnostic value of serum IgG, IgM and IgA in patients with uncomplicated urogenital Chlamydia trachomatis infection was compared with isolation in cell culture. C. trachomatis specific antibodies were determined with an enzyme linked immunofluorescent assay using elementary bodies from C. trachomatis serotypes E,F,H,I,J and LGV2 as antigens. At least two sera from each patient were tested and cultures were also established on the same day. Excluding the IgM titres in men, significantly more IgG, IgA and IgM and combinations of these antibodies were observed in culture positive patients. The sensitivity with which IgG titres in men or IgG and/or IgM titres in men and women could be determined, was significantly lower using C. trachomatis LGV2 as the only antigen than when all 6 antigens were used. The presence of 10 or more leucocytes in the urine sediment of men correlated positively with an IgG or an IgG and/or IgM titre.


A Case Series of Granulomatosis With Polyangiitis Primarily Diagnosed by Otological Manifestations.
To describe a case series of previously undiagnosed granulomatosis with polyangiitis (GPA) patients who presented primarily with otological manifestations. We report a series of patients visited at a neurotology clinic who were eventually diagnosed with GPA based on their otologic complaints and had no prior knowledge of having this condition. In this series, 10 (91%) patients presented with hearing loss (HL), more than half of which were bilateral (60%). Upon audiometric examination, all but 1 patient had mixed, conductive, or sensorineural HL. All patients presented with eustachian tube dysfunction (ETD), otitis media with effusion (OME), or both. Nasal endoscopy showed intranasal pathology in 3 (27%) patients. Otologic symptoms were improved in all patients after treatment with an average of 4 in-office follow-up appointments. GPA should be included in the differential diagnosis of adults with unexplained mixed hearing loss, new onset serous effusion, or acute otitis media in the absence of a previous history of ETD. Laboratory tests (ie, anti-neutrophil cytoplasmic autoantibody, erythrocyte sedimentation rate, and C-reactive protein) along with a urinalysis can aid in screening these patients. In cases in which the index of suspicion is high, repeated testing could reduce the risk of false negative findings.


Effects of glycidate on carbon dioxide fixation with isolated spinach chloroplasts.
Glycidate (2,3-epoxypropionate) stimulated CO(2) fixation in isolated spinach chloroplasts up to 100%. In the presence of glycidate the initial lag phase was abolished and the chloroplasts exported mainly 3-phosphoglycerate instead of dihydroxyacetone phosphate.Glycolate formation was not inhibited by glycidate, which is in agreement with the observation that preactivated ribulose-1,5-bisphosphate oxygenase is not inhibited by this compound. Furthermore, glycidate had no effect on electron transport (NADP reduction) and photophosphorylation, nor was a change in the coupling ratio observed.


Neuropilin-1: A Key Protein to Consider in the Progression of Pediatric Brain Tumors.
Neuropilins are transmembrane glycoproteins that play important roles in cardiovascular and neuronal development, as well as in immunological system regulations. NRP1 functions as a co-receptor, binding numerous ligands, such as SEMA 3 or VEGF and, by doing so, reinforcing their signaling pathways and can also interface with the cytoplasmic protein synectin. NRP1 is expressed in many cancers, such as brain cancers, and is associated with poor prognosis. The challenge today for patients with pediatric brain tumors is to improve their survival rate while minimizing the toxicity of current treatments. The aim of this review is to highlight the involvement of NRP1 in pediatric brain cancers, focusing essentially on the roles of NRP1 in cancer stem cells and in the regulation of the immune system. For this purpose, recent literature and tumor databases were analyzed to show correlations between NRP1 and CD15 (a stem cancer cells marker), and between NRP1 and PDL1, for various pediatric brain tumors, such as high- and low-grade gliomas, medulloblastomas, and ependymomas. Finally, this review suggests a relevant role for NRP1 in pediatric brain tumors progression and identifies it as a potential diagnostic or therapeutic target to improve survival and life quality of these young patients.


Computer models evaluating hand tremors in Parkinson's disease patients.
One of the most characteristic signs of Parkinson's disease (PD) is hand tremor. The MDS-UPDRS scale evaluates different aspects of the disease. The tremor score is a part of the MDS-UPDRS scale, which provides instructions for rating it, by observation, with an integer from 0 to 4. Nevertheless, this form of assessment is subjective and dependent on visual acuity, clinical judgment, and even the mood of the individual examiner. On the other hand, in many cases, existing computational models proposed to resolve the disadvantages of the MDS-UPDRS scale may have uncertainty in differentiating a category of a slight Parkinson tremor from voluntary movements. In this study, 554 measurements from Parkinson's patients, and 60 measurements from healthy subjects, were recorded with inertial sensors placed on the back of each hand. Five biomechanical indicators characterised the hand tremor. With these indicators, the three fuzzy inference models proposed can differentiate, in the first instance, the presence of postural or resting tremor from a normal movement of the hand, and if detected, to determine its severity. The fuzzy inference models allowed following the criteria of the MDS-UPDRS scale, providing an evaluation with an accuracy of two decimal digits and which, due to its simplicity, can be implemented in clinical environments. The assessments of three experts validated the computer model.


Developing a Biorelevant Dissolution Method for an Extrudable Core System (ECS) Osmotic Tablet.
The objective of this work is to develop a biorelevant dissolution method to support the clinical study for In Vitro In Vivo Correlation (IVIVC) of the first commercially approved single-layer extrudable core system (ECS) osmotic tablet - the 11 mg tofacitinib modified-release tablet. The dissolution conditions were selected through analysis of experimental work including several designed experiments (DoE). The Apparatus 2 (paddles) was selected over the Apparatus 1 (baskets) to minimize the dissolution test variability. The paddle speed was kept at 50 rpm to be conservative and because higher paddle speed did not offer statistically significant improvement in dissolution test variability. The buffer of 50 mM potassium phosphate at pH 6.8 was selected over other buffers at lower or acid pH as the in vivo drug release is expected to occur in the small intestinal region, where the pH is approximately neutral. Finally, the statistically designed experiments proved that use of the Japanese basket sinkers was effective in reducing dissolution variability and eliminating the artificial shift in dissolution profile caused by final pink color-coated tablets sticking to the dissolution vessel. Discriminatory power of the method was verified and the method was validated per ICH and FDA guidelines. Since a Level A IVIVC is established from the analysis of the results of both in vivo clinical study and in vitro dissolution testing, the method is proven to be biorelevant. It also serves a suitable quality control dissolution method.


The influence of bat echolocation call duration and timing on auditory encoding of predator distance in noctuoid moths.
Animals co-occur with multiple predators, making sensory systems that can encode information about diverse predators advantageous. Moths in the families Noctuidae and Erebidae have ears with two auditory receptor cells (A1 and A2) used to detect the echolocation calls of predatory bats. Bat communities contain species that vary in echolocation call duration, and the dynamic range of A1 is limited by the duration of sound, suggesting that A1 provides less information about bats with shorter echolocation calls. To test this hypothesis, we obtained intensity-response functions for both receptor cells across many moth species for sound pulse durations representing the range of echolocation call durations produced by bat species in northeastern North America. We found that the threshold and dynamic range of both cells varied with sound pulse duration. The number of A1 action potentials per sound pulse increases linearly with increasing amplitude for long-duration pulses, saturating near the A2 threshold. For short sound pulses, however, A1 saturates with only a few action potentials per pulse at amplitudes far lower than the A2 threshold for both single sound pulses and pulse sequences typical of searching or approaching bats. Neural adaptation was only evident in response to approaching bat sequences at high amplitudes, not search-phase sequences. These results show that, for short echolocation calls, a large range of sound levels cannot be coded by moth auditory receptor activity, resulting in no information about the distance of a bat, although differences in activity between ears might provide information about direction.


Identification of Fatty Acid Binding Protein 5 Inhibitors Through Similarity-Based Screening.
Fatty acid binding protein 5 (FABP5) is a promising target for development of inhibitors to help control pain and inflammation. In this work, computer-based docking (DOCK6 program) was employed to screen ∼2 M commercially available compounds to FABP5 based on an X-ray structure complexed with the small molecule inhibitor SBFI-26 previously identified by our group (also through virtual screening). The goal was discovery of additional chemotypes. The screen resulted in the purchase of 78 candidates, which led to the identification of a new inhibitor scaffold (STK-0) with micromolar affinity and apparent selectivity for FABP5 over FABP3. A second similarity-based screen resulted in three additional hits (STK-15, STK-21, STK-22) from which preliminary SAR could be derived. Notably, STK-15 showed comparable activity to the SBFI-26 reference under the same assay conditions (1.40 vs 0.86 μM). Additional molecular dynamics simulations, free energy calculations, and structural analysis (starting from DOCK-generated poses) revealed that R enantiomers (dihydropyrrole scaffold) of STK-15 and STK-22 have a more optimal composition of functional groups to facilitate additional H-bonds with Arg109 of FABP5. This observation suggests enantiomerically pure compounds could show enhanced activity. Overall, our study highlights the utility of using similarity-based screening methods to discover new inhibitor chemotypes, and the identified FABP5 hits provide a strong starting point for future efforts geared to improve activity.


Ocular disease caused by the trematode Philophthalmus lachrymosus in free-living kelp gulls (Larus dominicanus) of Brazil.
In this study, clinical, parasitological and histopathological findings of thirteen kelp gulls (Larus dominicanus) found infected with eyeflukes in Brazil are presented. Parasites detected in the ventral conjunctival fornix were identified as Philophthalmus lachrymosus [mean intensity of infection: 16 (5-36) worms/bird]. Eleven birds (85%) presented signs of systemic disease, such as emaciation, dehydration and depressed consciousness. Conjunctival hyperemia was observed in 22 eyes (85%). Keratitis, corneal ulcers, corneal abscess and chemosis were also detected in some eyes (4-8%). Histopathologic lesions, likely due to the parasite attachment to the conjunctiva, were found in the eyes of one infected bird that died from unrelated causes. Philophthalmosis by P. lachrymosus is here reported as a clinically relevant eye disease in kelp gulls.


Tandem dienone photorearrangement-cycloaddition for the rapid generation of molecular complexity.
A tandem dienone photorearrangement-cycloaddition (DPC) reaction of novel cyclohexadienone substrates tethered with various 2π and 4π reaction partners resulted in the formation of polycyclic, bridged frameworks. In particular, use of alkynyl ether-tethered substrates led to (3 + 2) cycloaddition to afford strained alkenes which could be further elaborated by intra- and intermolecular cycloaddition chemistry to produce complex, polycyclic chemotypes.


Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma.
A significant increase in the incidence of allergy and asthma has been observed during the past decades. The background of this phenomenon has not been well explained, but changes in lifestyle and habits are heavily discussed as contributing factors. Among these is a too clean environment, which may predispose individuals to increased sensitivity to allergic responses. Also the increase in dietary supplements including preservatives and colorants may contribute to this. In vitro, we and others have shown in freshly isolated human peripheral blood mononuclear cells that antioxidant compounds like vitamins C and E as well as food preservatives and colorants exert significant suppressive effects on the Th1 immune activation cascade. The effects observed may be based on the interaction of antioxidant compounds with proinflammatory cascades involving important signal transduction elements such as nuclear factor-κB. Although only obtained in vitro, these results show an anti-inflammatory property of compounds which could shift the Th1-Th2-type immune balance towards Th2-type immunity. This review article discusses the potential role of increased use of antioxidant food supplements as well as preservatives and colorants in the increase in allergy and asthma in the Western world.


The effect of personal characteristics on the validity of nutrient intake estimates using a food-frequency questionnaire.
To assess validity of the Nambour food-frequency questionnaire (FFQ) relative to weighed food records (WFRs), and the extent to which selected demographic, anthropometric and social characteristics explain differences between the two dietary methods. Inter-method validity study; 129-item FFQ vs. 12 days of WFR over 12 months. Community-based Nambour Skin Cancer Prevention Trial. One hundred and fifteen of 168 randomly selected participants in the trial (68% acceptance rate) aged 25-75 years. Spearman correlations between intakes from the two methods ranged from 0.18 to 0.71 for energy-adjusted values. Differences between FFQ and WFR regressed on personal characteristics were significantly associated with at least one characteristic for 16 of the 21 nutrients. Sex was significantly associated with differences for nine nutrients; body mass index (BMI), presence of any medical condition and age were each significantly associated with differences for three to six nutrients; use of dietary supplements and occupation were associated with differences for one nutrient each. There was no consistency in the direction of the significant associations. Regression models explained from 7% (riboflavin) to 27% (saturated fat) of variation in differences in intakes. The relative validity of FFQ estimates for many nutrients is quite different for males than for females. Age, BMI, medical condition and level of intake were also associated with relative validity for some nutrients, resulting in the need to adjust intakes estimates for these in modelling diet-disease relationships. Estimates for cholesterol, beta-carotene equivalents, retinol equivalents, thiamine, riboflavin and calcium would not benefit from this.


Dissecting dementia, depression, and drug effects in older adults.
As adults age, many changes in functioning occur, and dementia and/or depression may develop. Medications used to manage dementia and depression include selective serotonin reuptake inhibitors. The challenge for nurses is recognizing which behaviors, signs, and symptoms are the result of the dementia or depression and which are the result of the drug therapy. The purpose of this article is to present information to increase awareness of the complexities of care for older adults with dementia and/or depression and identify possible implications for practicing nurses.


[The Brandenburg Network Healthy Children: Early Prevention Shows Effectiveness].
The Brandenburg Network Healthy Children (NHC) is a regional health programme for families with toddlers (0-3) run by trained volunteers. Based on the analysis of School Entry Medical Examination (SEME), the study investigates the possible influence of NHC on children's health. A retrospective epidemiological analysis of the sociodemografic and health-related differences among subgroups nc and n-nc based on SEME, school year 2016/2017 (network children/nc: 1,152, not network children/n-nc: 20,954), using descriptive statistics; a logistic regression analysis assessing, for instance, the power of NHC's influence on health adjusting also for social status and region. Parents with low/middle social status and one-parent families participated more frequently in the NHC (p<0.001). Nc compared to n-nc brought check-up documents (94.3 / 91.5%, p<0.001) and vaccination certificates (95.7 / 91.7%, p<0.001) more frequently to SEME. A higher tetanus-diphtheria-pertussis booster rate was observed after network participation. The adjusted model showed nc were less likely to have incomplete (U2-U6) check-ups (OR 0.347 [95%-KI: 0.192-0.627, p<0.001]), vaccination gaps (OR 0.621 [95%-KI: 0.508-0.758, p<0.001]) and more likely to be "optimally cared for" (OR 1.355 [95%-KI: 1.175-1.562, p<0.001]). Children's health showed benefit from network participation.


Cytokeratin profiles in oral epithelial: a review and a new classification.
This article proposes a classification of oral epithelial and summarizes recent literature of cytokeratin expression in the oral cavity. The oral epithelial are subdivided into two major groups: superficial and deep epithelia. Epithelial lining the oral cavity, i.e., superficial, are essentially stratified squamous epithelia, with the exception of taste buds. The epithelium covering the dorsal tongue is a combination of keratinized and non-keratinized epithelia. Deep epithelia are of two kinds, odontogenic and glandular epithelia. This study provides a classification of the cytokeratins expressed in the oral cavity in healthy and pathological situations based on published data and our own studies. The profiles of these polypeptides in different oral epithelia should provide information that may be used in various disciplines of oral medicine.


Narrowing the FOXF1 distant enhancer region on 16q24.1 critical for ACDMPV.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder caused by heterozygous point mutations or genomic deletions involving FOXF1 or its 60-kb tissue-specific enhancer region mapping 270 kb upstream of FOXF1 and involving fetal lung-expressed long non-coding RNA genes and CpG-enriched sites. Recently, we have proposed that the FOXF1 locus at 16q24.1 may be a subject of genomic imprinting. Using custom-designed aCGH and Sanger sequencing, we have identified a novel de novo 104 kb genomic deletion upstream of FOXF1 in a patient with histopathologically verified full phenotype of ACDMPV. This deletion allowed us to further narrow the FOXF1 enhancer region and identify its critical 15-kb core interval, essential for lung development. This interval harbors binding sites for lung-expressed transcription factors, including GATA3, ESR1, and YY1, and is flanked by the lncRNA genes and CpG islands. Bisulfite sequencing of one of these CpG islands on the non-deleted allele showed that it is predominantly methylated on the maternal chromosome 16. Substantial narrowing and bisulfite sequencing of the FOXF1 enhancer region on 16q24.1 provided new insights into its regulatory function and genomic imprinting.