Opinions of Tutors and Students about Effectiveness of PBL in Dokuz Eylul University School of Medicine.
The aim of this study is to determine the opinions of tutors and students about the effectiveness of Problem-based Learning in Dokuz Eylul University School of Medicine. A questionnaire with a five-point Likert scale, with 1:minimum, 5;maximum, rating PBL effectiveness was administered in February and March of 2001 to tutors and students. Response rates of tutors and students were respectively 65.0% (130 out of 201) and 82.4% (346 out of 420). The reliability of the scale was high (Cronbach α= 0.90). Ratings of tutors and students respectively on identified outcomes of PBL varied between 3.80-4.69 and 3.69-4.27 out of 5 points. Both groups gave high ratings to the areas of clinical reasoning, communication and problem solving and gave lower ratings to gaining basic science knowledge. Basic science tutors rated the areas of problem solving, gaining basic science knowledge and intrinsic motivation of students significantly higher than did clinical science tutors. According to the results of this study, tutors and students opinions about PBL outcomes were similar to those previously reported in the literature. Both groups had positive opinions about PBL's effectiveness. As has been reported in other studies, tutors and students gave the lowest ratings to the area of gaining basic science knowledge. However, the ratings of basic science tutors were higher than those of clinical science tutors in this area. This may be due to preexisting beliefs of clinical science tutors regarding the effectiveness of PBL for teaching factual basic science knowledge.


Trends in long term growth outcome: comparison of two birth cohorts (year 2007-08 and year 2015-16).
Very low birth weight (VLBW) infants comprise between 4% and 8% of live-births and about one-third of deaths during the neonatal period. The objective of the study is to evaluate and compare the long-term growth outcomes of VLBW infants among two different birth cohorts: Cohort 2007-08 (cohort 1) and cohort 2015-16 (cohort 2), in a cross-sectional observational study. The neonatal and perinatal data of cohort 1 was collected from available trial data and the same data from cohort 2 was collected from patient case files and patient history. The primary outcome of the study was to compare the growth outcomes of VLBW infants attending the follow-up clinic between 12 and 18 months of corrected age from two different birth cohorts. Respectively, 238 and 268 infants were eligible for inclusion in cohort 1 and 2. Among the eligible infants, 148 infants in cohort 1 and 178 infants in cohort 2 were available for primary outcome assessment during the recruitment phase. The weight and length at corrected age (12 to 18 months) is significantly higher in cohort 2 compared to that in cohorts 1 although the mean age at assessment is similar between the two groups. There is a significant reduction in the incidence of underweight in infants that belonged to cohort 2. The proportions of infants who are underweight at follow-up were significantly lower in cohort 2 when compared to cohort 1, and there were no significant differences in the incidence of stunting and microcephaly among both the cohorts.


Is it possible to eliminate sutures in open (Lichtenstein technique) and laparoscopic (totally extraperitoneal endoscopic) inguinal hernia repair? A randomized controlled trial with tissue adhesive (n-hexyl-α-cyanoacrylate).
The morbidity linked to the use of sutures in inguinal hernioplasty is well known. Tissue adhesives may be an alternative, so as to be able to improve levels of postoperative comfort, but clinical experience using them is limited. The aim of this study is to evaluate the efficiency of cyanoacrylate as a substitute for sutures in the treatment of inguinal hernias. Randomized clinical trial in abdominal wall unit. A total of 208 patients were operated upon for inguinal hernias of which 102 were unilateral hernias via open surgery using the Lichtenstein technique, randomized to receive prolene sutures (n = 52) or n-hexyl-α-cyanoacrylate glue (n = 50) and 106 were patients with bilateral inguinal hernias operated upon via totally extraperitoneal laparoscopy and randomized to receive either tackers (n = 54) or glue (n = 52). The primary endpoints were pain and recurrence. Secondary endpoints were operating time, postoperative morbidity, pain, and analgesic consumption. No morbidity associated with the use of the glue existed. The use of glue significantly reduced the mean of surgical time (12 minutes in open surgery, 13 minutes in laparoscopic surgery), pain, and analgesics consumption, both via the open and laparoscopic approaches (P < .001). After 1 year the adhesive did not change the recurrence rate in either of the approaches. The economic analysis shows potential yearly savings of 123 916.3 Euros. Substituting sutures with glue (n-hexyl-α-cyanoacrylate) in open or laparoscopic inguinal hernioplasty is safe with less postoperative pain and the same possibilities of recurrence.


MHC VARIATION IN THE ENDANGERED GILA TOPMINNOW.
Sequence variation at a major histocompatibility complex (MHC) gene, assumed to be involved in parasite and pathogen resistance, was examined in the endangered Gila topminnow (Poeciliopis o. occidentalis), from the four watersheds where they remain in the United States. This is the first estimate of variation in MHC genes in natural populations of an endangered species. The population that has experienced the most bottlenecks historically was monomorphic for MHC variation. Another population, which earlier had been found to be the only population polymorphic for allozymes, had five MHC alleles, four different from those found in the other populations. Overall, nine different alleles were found. The four populations were highly divergent at MHC with four of the six population pairs not sharing any alleles. However, the magnitude of differentiation between populations on the amino-acid level varied fivefold for the populations that shared no alleles. Using single-stranded conformational polymorphism (SSCP), these alleles segregated consistently with Mendelian expectations in families. Because of the high genetic differentiation between these populations for a potentially adaptive gene, we recommend that the four watersheds be examined further for separate conservation and management.


Hydrogenation of High-Density Polyethylene during Decompression of Pressurized Hydrogen at 90 MPa: A Molecular Perspective.
To investigate changes in the physical and chemical properties of high-density polyethylene (HDPE) upon the rapid release of hydrogen gas at a pressure of 90 MPa, several characterization techniques have been employed, including optical microscopy, scanning electron microscopy, X-ray diffraction, differential scanning thermal analysis, and attenuated total reflectance Fourier-transform infrared spectroscopy. The results showed that both physical and chemical changes occurred in HDPE upon a rapid release of hydrogen gas. Physically, a partial hexagonal phase was formed within the amorphous region, and the overall crystallinity of HDPE decreased. Chemically, hydrogenation occurred, leading to the addition of hydrogen atoms to the polymer chains. Oxidation also occurred, for example, the formation of ester -C=O groups. Crosslinking and an increase in -CH3 end termination were also observed. These changes suggest that structural transformation and chemical modification of HDPE occurred upon the rapid release of hydrogen gas.


Rapid characterization of vegetation structure with a Microsoft Kinect sensor.
The importance of vegetation structure and biomass in controlling land-atmosphere exchange is widely recognized, but measurements of canopy structure are challenging, time consuming, and often rely on destructive methods. The Microsoft Kinect is an infrared sensor designed for video gaming that outputs synchronized color and depth images and that has the potential to allow rapid characterization of vegetation structure. We compared depth images from a Kinect sensor with manual measurements of plant structure and size for two species growing in a California grassland. The depth images agreed well with the horizontal and vertical measurements of plant size made manually. Similarly, the plant volumes calculated with a three-dimensional convex hulls approach was well related to plant biomass. The Kinect showed some limitations for ecological observation associated with a short measurement range and daytime light contamination. Nonetheless, the Kinect's light weight, fast acquisition time, low power requirement, and cost make it a promising tool for rapid field surveys of canopy structure, especially in small-statured vegetation.


Population pharmacokinetics of polymyxin B in patients with liver dysfunction.
Polymyxin B (PMB) is widely used to treat infections caused by multidrug-resistant Gram-negative pathogens. Currently, the pharmacokinetic data of PMB in patients with liver dysfunction are limited. This study aimed to develop a population pharmacokinetic (PopPK) model of PMB in patients with liver dysfunction and identify the factors affecting PMB pharmacokinetics. We conducted a retrospective pharmacokinetic study involving 136 adults with different levels of liver function. Nonlinear mixed effects modelling was used to develop a PopPK model of PMB. Monte Carlo simulation was used to design PMB dosage schedules across various liver and renal functions. PMB pharmacokinetic analyses included 401 steady-state concentrations in 136 adult patients. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. The typical population value of PMB clearance was 2.43 L/h and the volume of distribution was 23.11 L. This study revealed that creatinine clearance (CrCL) and Child-Pugh class were significantly associated with PMB pharmacokinetic parameters; however, clinically relevant variations of dose-normalized drug exposure were not significant. For patients with a minimum inhibitory concentration of ≤0.5 mg/L, the appropriate dose was 40-75 mg/12-h. When the dose exceeded 100 mg/12-h, the risk of nephrotoxicity increased significantly. This study provided PMB pharmacokinetic information for patients with liver dysfunction. Patients with renal and liver dysfunctions may not require an initial dose adjustment. Rather than PopPK-guided dose adjustment, therapeutic drug monitoring of PMB plays a more direct role in optimizing dosing regimens based on its therapeutic window.


Fragmentation characteristics of b(n) (n=2-15) ions from protonated peptides.
The fragmentation reactions of protonated oligoalanines (trialanine, tetraalanine and pentaalanine) and the fragments present in the electrospray ionization (ESI) mass spectrum of polyalanine have been studied by collisionally activated dissociation (CAD) mass spectrometry (MS(2) and MS(3) experiments). The MS(n) experiments provided strong evidence that the m/z 71n+1 ion series in the ESI mass spectrum of polyalanine is a b(n) series. These ions are formed via the b(n) -y(m) pathway of amide bond cleavage, which results in the formation of a proton-bound complex of an oxazolone and a peptide/amino acid. Also, the MS(2) spectra of the b(n) series from polyalanine revealed that the chain length of b(n) ions influences significantly the dissociations taking place. For example, b(n) ions start losing H(2)O at n ≥5 and the losses of CO and CO+NH(3) decrease in intensity from b(2) to b(15). The elimination of H(2)O+NH(3) and the elimination of 61 mass (HN=C=O+H(2)O) commence with b(6); their abundances initially increase up to ~ b(8)-b(9) and then gradually decrease until b(15) (largest fragment studied). The tandem mass spectrometry experiments help to elucidate the dissociation mechanisms of the observed structures of biopolymer fragments.


Relationships among carbonated apatite solubility, crystallite size, and microstrain parameters.
The use of the metastable equilibrium solubility (MES) concept to describe the solubility properties of carbonated apatites (CAPs) and human dental enamel (HE) has been well established in previous studies using a range of CAPs with varying carbonate contents and crystallinities. It was shown in these studies that the mean value of the CAP MES is directly related to the broadening parameter full width at half maximum (FWHM) of the 002 reflection of the X-ray diffraction profile. The apparent solubility of the CAPs increased monotonically with an increase in the broadening of the diffraction peaks, and when this peak broadening was taken into account, carbonate had no additional effect upon the MES. The broadening of the diffraction peaks has been used as an indicator of crystallinity, and is generally influenced by both crystallite size and microstrain. The purpose of the present study was to extract the crystallite size and microstrain parameters separately from the X-ray diffraction peaks and then to determine their relationships to the corresponding MES values. The samples studied were CAPs synthesized by precipitation from Ca(NO3)2 and NaH2PO4 solutions in carbonate containing media at temperatures of 95, 80, and 70 degrees C, and powdered HE. The crystallite size and microstrain parameters were determined simultaneously with the refinement of the structural parameters with the Rietveld method of whole-pattern-fitting structure-refinement. A modified pseudo-Voigt function was used to model the observed peak profiles. The MES distributions for the CAPs and HE were determined by a previously described method. The results of this study showed that the CAPs possessed an MES distribution and therefore provided further support that MES distribution is a common phenomenon, regardless of the method of CAP synthesis. The crystallite size decreased and the microstrain increased with increasing carbonate content and decreasing temperature of synthesis of the CAPs. A plot of the mean of the MES distribution versus the microstrain parameter showed that the apparent solubility of the CAPs and HE correlated very well with the microstrain parameter. On the other hand, a plot of the mean of the MES distribution versus the crystallite size parameter showed a poor correlation between MES and crystallite size. These findings support a view that microstrain, rather than crystallite size, is the dominant factor governing the effective solubility of the CAPs and dental enamel.


Attention-Based Fusion of Ultrashort Voice Utterances and Depth Videos for Multimodal Person Identification.
Multimodal deep learning, in the context of biometrics, encounters significant challenges due to the dependence on long speech utterances and RGB images, which are often impractical in certain situations. This paper presents a novel solution addressing these issues by leveraging ultrashort voice utterances and depth videos of the lip for person identification. The proposed method utilizes an amalgamation of residual neural networks to encode depth videos and a Time Delay Neural Network architecture to encode voice signals. In an effort to fuse information from these different modalities, we integrate self-attention and engineer a noise-resistant model that effectively manages diverse types of noise. Through rigorous testing on a benchmark dataset, our approach exhibits superior performance over existing methods, resulting in an average improvement of 10%. This method is notably efficient for scenarios where extended utterances and RGB images are unfeasible or unattainable. Furthermore, its potential extends to various multimodal applications beyond just person identification.


Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology.
Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. This portion of the NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.


Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue.
It remains unclear which gene induction effectively generates photoreceptor-specific phenotypes from nonretinal tissues. The purpose of this study was to determine whether Crx and Otx2--homeobox genes related to photoreceptor development--can induce the generation of these phenotypes in cells derived from adult ciliary and iris tissue and in mesencephalon-derived neural stem cells. Crx and Otx2 were transferred into adult rat ciliary- and embryonic mesencephalon-derived neurospheres and adult rat iris-derived cells with the aid of a recombinant retrovirus. The presence of photoreceptor-specific phenotypes was confirmed by immunocytochemistry and Western blot analysis. More than 90% of the Crx- and Otx2-transfected ciliary- and iris-derived cells exhibited rod opsin immunoreactivity, whereas few of the similarly transfected mesencephalon-derived neural stem cells expressed rod opsin. At least two additional key components of the phototransduction cascade, recoverin and Gdeltat1, were expressed by Crx- and Otx2-transfected iris-derived cells. Crx and Otx2 effectively induced the generation of photoreceptor-specific phenotypes from ciliary- and iris-derived cells. That both Crx and Otx2 induced phenotype generation in cells derived from iris or ciliary tissue may suggest an approach to photoreceptor cell preparation for retinal transplantation.


A Comparison of Multimodal Analgesic Approaches in Institutional Enhanced Recovery After Surgery Protocols for Colorectal Surgery: Pharmacological Agents.
Enhanced Recovery After Surgery (ERAS®) protocols are the cornerstone of improved recovery after colorectal surgery. Their implementation leads to reduced morbidity and shorter hospital stays while attenuating the surgical stress response. Multimodal analgesia is an important part of ERAS protocols. We compared and contrasted protocols from 15 institutions to test our hypothesis that there is a fundamental consensus among them. ERAS protocols for open and laparoscopic colorectal surgery were compared from 15 different healthcare facilities. We examined each institution's approach to multimodal analgesia related to the use of oral and intravenous analgesics. Preoperative, intraoperative, and postoperative management was examined. All but three protocols used preoperative multimodal analgesics, with acetaminophen, celecoxib, and gabapentin being the most common. Intraoperative recommendations included the use of ketamine, lidocaine, magnesium, and ketorolac. Some protocols advocated for the use of opiates, while others aimed to minimize total opioid dose. In the postoperative period, the three most utilized agents were acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. There were many similarities and some significant differences among ERAS protocols examined. Acetaminophen was the most widely used nonopioid agent and along with NSAIDs offers a benefit with respect to postoperative analgesia, opioid-sparing effects, earlier ambulation, and reduction in postoperative ileus. Gabapentin was widely used as it may reduce opioid consumption within the first 24 hours postoperatively. Lidocaine infusion was recommended if there were contraindications to or failure of epidural anesthesia. Ketamine is frequently recommended due to its analgesic, antihyperalgesic, antiallodynic, and antitolerance properties. Differences in approaches may be due to both institutional- and provider-level factors.


Alveolar bone loss in 5-year-old New Zealand children: its prevalence and relationship to caries prevalence, socio-economic status and ethnic origin.
This study investigated the prevalence of alveolar bone loss (ABL) in 5-year-old New Zealand children. The relationship of bone loss with the prevalence of caries, socio-economic status and ethnic origin was examined. Standardized bite-wing radiographs from 317 children were used to examine the alveolar bone in 1784 sites. Questionable bone loss (QBL) was evident in 8.5% of the children and definite bone loss (DBL) in 2.1%. The children with suitable radiographs had a mean dmft of 1.8 +/- 2.9 and mean dmfs of 2.7 +/- 5.0. When the children were divided into 3 groups having no bone loss (NBL), QBL only or DBL, analysis of variance on the logarithmic transformation of both the dmft and dmfs scores showed significant differences among the groups. Post hoc tests showed that the means for the DBL group were significantly different from those of the other 2 groups for both dmft and dmfs scores. Logistic regression analysis indicated that the odds ratio for having definite alveolar bone loss was slightly increased in children with a dmft of > or = 9.


Effective temperature for an intermittent bistable potential.
Thermodynamics of far-from-equilibrium systems often require measurement of effective parameters such as temperature. Whether such approach is valid for the general case of resetting protocols, active systems, or of confined systems under time-varying fields is still under investigation. We report on the effect of switching ON-OFF of an asymmetric bistable potential to the mean first passage time (MFPT) of a probed particle to go from one potential minima to the other. Experimental results coupled with numerical simulations shows the potential becoming more symmetric at slow switching. Moreover, the MFPT deviates from equilibrium condition with an effective temperature, Teff < T, at slow switching but approaches room temperature, T, at fast switching. For each switching rate, we quantify how far the system is from equilibrium by measuring deviation from a detailed balance like relation and the net circulation of flux present in phase-space. Both analysis suggest equilibrium condition are met at high switching.


Expert Consensus on Cosmetic Outcomes After Treatment of Actinic Keratosis.

Dermatologists treat actinic keratosis (AK) primarily because these lesions have the potential to progress to invasive squamous cell carcinoma. Patients, on the other hand, generally seek treatment to remove the lesions and achieve an improved appearance of their skin following treatment. In selecting a treatment option for AK, dermatologists should consider post-treatment cosmesis, because cosmetic outcomes differ across AK treatments. To obtain expert opinion on the cosmetic sequelae related to chronically photodamaged skin and the treatment of AK, an expert panel meeting among dermatologists was conducted in February 2016. These experts reviewed current treatment options for photodamage, including AK, and discussed the relative merits of the various cosmetic assessments commonly used by investigators and patients in both clinical trial and dermatology practice settings. A main goal of the expert panel meeting was to propose assessment tools that could be specifically designed to characterize cosmesis results after treatment of AK. The panel agreed that existing tools for measurement of cosmetic outcomes following treatment of photodamage could also be used to evaluate cosmesis after treatment of AK. Digital photography is probably the best method used for this, with validation by other technologies. Better measurement tools specifically for assessing cosmesis after AK treatment are needed. Once they are developed and validated, regulatory agencies should be educated about the importance of including cosmetic outcomes as a component of product labeling.

J Drugs Dermatol. 2017;16(3):260-265.
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An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors.
Prostate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv-C(H)3 dimer, 80 kDa), can localize specifically and image PSCA-expressing xenografts at 21 h post-injection. However, the humanization and antibody fragment reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging contrast with affinity matured minibodies. Yeast scFv display, involving four rounds of selection, was used to generate the three affinity matured antibody fragments (A2, A11, and C5) that were reformatted into minibodies. These three affinity matured anti-PSCA minibodies were characterized in vitro, and following radiolabeling with (124)I were evaluated in vivo for microPET imaging of PSCA-expressing tumors. The A2, A11, and C5 minibody variants all demonstrated improved affinity compared to the parental (P) minibody and were ranked as follows: A2 > A11 > C5 > P. The (124)I-labeled A11 minibody demonstrated higher immunoreactivity than the parental minibody and also achieved the best microPET imaging contrast in two xenograft models, LAPC-9 (prostate cancer) and Capan-1 (pancreatic cancer), when evaluated in vivo. Of the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study.


Spin-Orbit Coupling Drives Femtosecond Nonadiabatic Dynamics in a Transition Metal Compound.
Transient absorption measurements conducted using broadband, 6 fs laser pulses reveal unexpected femtosecond dynamics in the [IrBr6]2- model system. Vibrational spectra and the X-ray crystal structure indicate that these dynamics are not induced by a Jahn-Teller distortion, a type of conical intersection typically associated with the spectral features of transition metal compounds. Two-dimensional electronic spectra of [IrBr6]2- contain 23 cross peaks, which necessarily arise from spin-orbit coupling. Real-valued 2D spectra support a spectroscopic basis where strong nonadiabatic coupling, ascribed to multiple conical intersections, mediates rapid energy relaxation to the lowest-energy excited state. Subsequent analysis gives rise to a more generalized description of a conical intersection as a degeneracy between two adiabatic states having the same total angular momentum.


A case-control study of the relationship between visceral fat and development of uterine fibroids.
Relationship between visceral fat and development of uterine fibroids in adult women was investigated. A total of 89 patients with uterine fibroids treated in the First Hospital of Hebei Medical University from April 2016 to April 2018 were enrolled. Another 81 healthy women without uterine fibroids receiving physical examination in the same period were selected as the control group. Self-designed questionnaires were used to investigate the general conditions of the subjects, bioelectrical impedance analysis was employed to analyze obesity-related indicators, and their correlation with the risk of uterine fibroids was explored. Visceral fat area (VFA), body mass index (BMI), body fat percentage, waist circumference, waist-height ratio and waist-hip ratio were positively correlated with the incidence rate of uterine fibroids, and the odds ratio (OR), 95% confidence interval (CI) was 3.910 (2.029, 7.536), 2.716 (1.444, 5.110), 4.335 (1.507, 12.469), 2.881 (1.531, 5.423), 3.837 (1.914, 7.692) and 7.707 (3.501, 16.965), respectively. VFA and body fat percentage were correlated with the size of uterine fibroids, but the correlations were relatively weak. With the increase in the VFA, BMI, waist circumference, waist-height ratio, and waist-hip ratio, the risk of uterine fibroids was elevated. The BMI, VFA and waist circumference of patients with uterine fibroids were gradually increased with increasing age, showing statistically significant differences. Increased body fat (especially abdominal visceral fat) is able to enhance the risk of uterine fibroids. For perimenopausal women, the waist-hip ratio measured can be used as an indicator screening high-risk groups of uterine fibroids. This method is simple, easy and inexpensive. At the same time, providing nutrition guidance and changing diet and exercise habits are important measures to prevent the development of uterine fibroids.


[The control of somatosensory area II of cerebral cortex on nucleus raphe magnus and its relation with nucleus accumbens].
Our previous work have demonstrated that the stimulation of somatosensory area II (Sm II) of cerebral cortex or N. accumbens (NAc) could activate nucleus raphe magnus (NRM), producing analgesia. The aim of this work is to study whether the effect of activation of Sm II on neurons in NRM is related to NAc. The spontaneous discharges of NRM neurons and their nociceptive responses induced by stimulation of tail tip were recorded extracellularly with glass microelectrode. The effects of stimulation of Sm II on the NRM neurons were observed before and after lesion of NAc. Before lesion of NAc, the stimulation of Sm II could activate NRM neurons, obviously increasing the firing rates in 0-10 minutes after stimulation (P < 0.05-0.01), and their nociceptive responses were decreased in 0-10 and 20 minutes (P < 0.01-0.001). After lesion of NAc, the firing rates having no clear change, and their nociceptive responses were even slightly enhanced. It is suggested that the effect of activation of Sm II on NRM neurons may need the relay via the NAc.


Dental management of patients with a history of bisphosphonate therapy: clinical dilemma.
Bisphosphonate osteonecrosis, BON, was recently described in the literature. Lack of scientific evidence explaining the pathophysiologic mechanisms involved in the development of this oral complication has generated uncertainties about proper management of patients treated with a bisphosphonate. This manuscript discusses the dental management of two breast cancer patients treated with intravenous bisphosphonates as part of their cancer management and who developed oral disease. Clinical management decisions will be presented as well as the treatment outcomes.


Genetic variant in APE1 gene promoter contributes to cervical cancer risk.
Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway, which plays an important role in repairing DNA damage caused by oxidation and alkylation. However, the exact mechanism of APE1 associated with cervical cancer risk is still unknown. In this study, we explored whether the APE1 -656T>G polymorphism contributed to the risk of cervical cancer. In the hospital-based case-control study, 306 cervical cancer cases and 306 cancer-free controls were genotyped for the APE1 -656T>G polymorphism using the polymerase chain reaction restriction fragment length polymorphism method. Luciferase reporter assay and electrophoretic mobility shift assay were used to evaluate the APE1 transcriptional activity and the binding ability of transcriptional factors to the APE1 promoter, respectively. Logistic regression analysis showed that individuals with the APE1 -656 TG/GG genotypes had a significantly reduced risk of cervical cancer compared with the TT genotype (adjusted odds ratio, 0.61; 95% confidence interval, 0.42-0.89). The luciferase assays in 3 cell lines showed that the APE1 -656T>G substitution can increase the expression of APE1, which was consistent with the finding of association study. Electrophoretic mobility shift assay further indicated that the APE1 -656T>G polymorphism enhanced the binding affinity of transcriptional factors to the promoter region. These findings suggested that the APE1 -656T>G polymorphism was associated with cervical cancer risk in a Chinese population by affecting the binding affinity of transcriptional factors to the promoter, leading to an increased expression level of APE1.


Monitoring Changes in Lower-Limb Strength and Power in Elite Athletes With the Countermovement-Jump and Keiser Leg-Press Tests.
To determine the utility of countermovement-jump and Keiser leg-press tests for tracking changes in elite athletes of different sports. Elite athletes of the Norwegian Olympic Federation (126 individuals from 18 sports) performed countermovement-jump and Keiser tests on 2 to 11 occasions between 2014 and 2021. Separate analyses were performed for male and female alpine skiing, male and female handball, male ice hockey, and males and females of other sports. Means and standard deviations of consecutive change scores were combined with short-term error of measurement (3.7%-7.0%) and smallest important changes (2.0%-3.6%, defined by standardization) to determine the proportions of athletes who experienced decisive changes in 2 senses: first, the athlete did not get substantially worse or better (>90% chance of either), and second, the athlete did get substantially worse or better (>90% chance of either). Averaged over sports, Keiser peak power and relative peak power had the highest proportions of decisive changes in the first (60% and 55%) and second senses (25% and 28%). The velocity intercept of the force-velocity relationship had the lowest proportions in the first and second senses (29% and 11%), while jump height, Keiser mean power, relative mean power, the force intercept, and the slope of the force-velocity relationship had similar proportions (40%-53% and 15%-21%). With the possible exception of the Keiser test velocity intercept, the proportions of observed decisive changes in elite athletes using Keiser measures and countermovement-jump height between tests appear adequate for the measures to be useful for routine monitoring.


[Experimental and clinical study of adoptive immunotherapy combined with preadministration of OK-432: a method to augment the therapeutic effect].
Our previous method of adoptive immunotherapy using IL2-cultured autologous lymphocytes consists of (1) in vitro sensitization by sonicated autologous tumor extract, (2) the induction and proliferation of active CTL by crude IL2, and (3) the preadministration of OK-432 for the augmentation of the therapeutic effect. Here we describe a new method to augment the therapeutic effect of OK432-combined AIT. In BALB/c mice with advanced malignant ascites (MOPC 104E), serial therapy with OK-432, cyclophosphamide and AIT significantly prolonged the survival compared with other therapeutic schedules through synergism between host's effector cells induced by immuno-chemotherapy and transferred killer cells. Many patients with advanced malignancies, for example, unresectable gastrointestinal cancer, locally advanced breast cancer or lung metastases of breast cancer, respond to such immuno-chemo-lymphocytotherapy, while previous OK432-combined AIT was effective only in malignant pleural effusion or metastatic liver tumor from breast cancer or peritoneal dissemination of gastric cancer.


Identification and Characterization of Escherichia coli, Salmonella Spp., Clostridium perfringens, and C. difficile Isolates from Reptiles in Brazil.
Considering the increasing popularity of reptiles as pets and their possible role as reservoirs of pathogenic microorganisms, the aim of this study was to isolate Escherichia coli, Salmonella spp., Clostridium perfringens, and C. difficile strains from reptiles in Brazil and to characterize the isolated strains. The characterization was based on phylogenetic typing of E. coli, identification of virulence genes of E. coli, C. perfringens, and C. difficile, serotyping of Salmonella spp., ribotyping and MLST of C. difficile and antimicrobial susceptibility test of pathogenic strains. Cloacal swabs were collected from 76 reptiles, of which 15 were lizards, 16 chelonians, and 45 snakes, either living in captivity, in the wild, or as companion animals. E. coli was isolated from 52 (68.4%) reptiles, of which 46 (88.4%) were characterized as phylogroup B1. The virulence factor CNF1 of E. coli was found in seven (9.2%) sampled animals, whereas the gene of EAST1 was found in isolates from two (2.6%) reptiles. Three isolates positive for CNF1 were resistant to cephalothin, one of which was also resistant to ciprofloxacin, trimethoprim/sulfamethoxazole, and chloramphenicol, being then classified as multidrug resistant strain (MDR). Salmonella enterica was identified in 26 (34.2%) reptiles, of which 13 belonged to the subspecies enterica. Serotypes such as S. Mbandaka, S. Panama, S. Infantis, S. Heidelberg, and S. Anatum were identified. One isolate of S. enterica subsp. houtenae was resistant to cephalothin and ciprofloxacin. C. perfringens type A was isolated from six (7.8%) animals. C. difficile was isolated from three (3.9%) reptiles. Two of these isolates were toxigenic and classified into ribotypes/MLST 081/ST9 and 106/ST42, which have been previously reported to infect humans. In conclusion, reptiles in Brazil can harbor toxigenic C. difficile and potentially pathogenic E. coli and Salmonella enterica subsp. enterica, thus representing a risk to human and animal health.


Nano-Web Cobalt Modified Silica Nanoparticles Catalysts for Water Oxidation and MB Oxidative Degradation.
Dioxygen generating materials, using water as oxygen source, can be used as catalysts in hypoxic environments. Cobalt(II) modified silica (SiO2@NPCo) nanoparticles were synthesized through coordination of cobalt(II) ions with nitrogen atoms from 2-acetylpyridine modified silica (SiO2@NP). The SiO2@NPCo nanoparticles further reacted with 1,3,5-benzenetricarboxylic acids, forming porous nano-web nanoparticles (SiO2@NPCoCOOH). The synthesized SiO2@NPCoCOOH nanoparticles were demonstrated as better white LED light driven photochemical catalysts for oxidation of water than individual nanoparticles (SiO2@NPCo). Moreover, the SiO2@NPCoCOOH/water system could decrease the content of methylene blue (MB) in solution and therefore, the nanoweb cobalt(II) modified silica nanoparticles can be environmentally friendly catalysts for oxidative degradation of MB, using water as the oxygen source.


Spectral broadening and diffusion by torsional motion in biphenyl.
We have studied biphenyl by time-dependent density-functional theory. In particular, we have analyzed the dependence of singlet excitation energies and transition dipoles on the torsional angle between the phenyl groups. The torsional spectrum has been computed quantum mechanically as well as semiclassically in order to understand how this influences the broadening of absorption and luminescence spectra. Our results are in best agreement with supersonic jet spectroscopy data, but also fit astonishingly well to spectra of biphenyl in condensed phase. Furthermore, we compare the torsional and vibrational relaxation and discuss qualitatively the general consequences for poly-para-phenylenes and related conjugated polymers as poly-thiophenes, considering, in particular, how side chains and solvents may affect the optical spectra.


Six-year regression and progression of cervical lesions of different human papillomavirus viral loads in varied histological diagnoses.
This study aims to evaluate human papillomavirus (HPV) viral loads as a biomarker for triage into colposcopy and cervical intraepithelial neoplasia grade 2 (CIN2) therapy to reduce the colposcopy referral rate and CIN2 overtreatment in low-resource settings. In 1999, 1997 women aged 35 to 45 years in Shanxi, China, received 6 cervical screenings with pathological confirmation. In 2005, 1461 histologically normal women, 99 with CIN grade 1 (CIN1), and 30 with CIN2 or worse (CIN2+) were rescreened in a follow-up study. Human papillomavirus was detected by Hybrid Capture 2. Viral load, estimated by the ratio of relative light units to standard positive control (RLU/PC), was categorized into 4 groups: negative (<1.0), low (≥1.0, <10.0), moderate (≥10.0, <100.0), and high (≥100.0). We estimated the cumulative incidence of CIN2+ by viral load subgroups and calculated adjusted hazard ratios for CIN2+ using Cox proportional hazards regression. Cumulative incidence of CIN2+ increased with baseline HPV viral loads among normal women and women with CIN1 at baseline (P(-trend) < 0.001). Repeat moderate-high viral load was associated with the highest risk for CIN2+ (adjusted hazard ratio, 188.8; 95% confidence interval, 41.2-864.1). Raising the ratio of relative light units to standard positive control cutoff from 1.0 to 10.0 for colposcopy greatly reduced the referral rate from 18.1% to 12.9%. It also increased the specificity (84.8% vs 90.4%), the positive predictive value (22.5% vs 28.9%), and the positive likelihood ratio (6.4 vs 8.9), yet with loss of sensitivity by 12% (97.6% vs 85.7%). Among women with CIN2 at baseline, 56% regressed to normal, 24% regressed to CIN1, 4% remained CIN2, and 16% progressed to CIN grade 3 or worse. Locales using HPV testing as the primary screening method and lacking high-quality cytology-based screening should consider viral load as an alternative to colposcopy triage for women older than 35 years. Viral loads may also predict CIN2 progression until additional biomarkers become available.


Pulmonary infarction due to vascular stent migration.
The case of a patient who developed pulmonary infarction after a vascular stent migrated to her pulmonary artery is presented. Stent migration is a known complication of vascular stents. The incidence is reported to be as low as 3%. Cases have been reported of successful retrieval of the stents. There are also reports of the stents being left in place without attempts to retrieve them, due to lack of symptoms. In this case, we opted to monitor the patient, despite the presence of pulmonary infarction. She appears to be tolerating the stent without any further complications.


Autonomous and directional flow of water and transport of particles across a subliming dynamic crystal surface.
Chemical and morphological traits of natural substrates that can propel and transport fluids over their surfaces have long provided inspiration for the engineering of artificial materials that can harvest and collect water from aerial humidity. Here we report that the gradual widening of parallel microchannels on a surface of a slowly subliming hexachlorobenzene crystal can promote the autonomous and bidirectional transduction of condensed aerial water. Driven by topology changes on the surface of the crystal and water exchange with the gas phase, droplets of condensed water migrate over the crystal. These droplets are also able to transport silver particles and other particulate matter, such as dust. The velocity of the particles was shown to be dependent on both the sublimation rate of the crystal and the relative humidity of its environment. This example of a sublimation-powered water flow demonstrates that topological surface changes accompanying crystal phase transitions can be harnessed to transport liquid and solid matter over surfaces.


Studies of intestinal microflora. VII. Effect of diet and fecal microbial flora on survival of animals exposed to x irradiation.
Changes in the numbers and ratios of bacteria in the feces of rats were produced by administration of three different diets-grain, meat alone, and meat plus lactose. After significant alterations in the intestinal flora had developed, the animals were exposed to a midlethal dose of X irradiation (1,550 R). This treatment led to 100% deaths in rats in which the numbers of coliforms were increased by diet prior to irradiation. Changes in the numbers of lactobacilli appeared to play no role in determining the responses to X-ray exposure. When little or no change was produced by diet and when "normal" microflora was present, the fatality rate was reduced to 60%, and the rate of deaths was retarded when compared with that of the animals in which coliforms were increased.


A L-glutamine binding protein modified MNM structured optical fiber biosensor based on surface plasmon resonance sensing for detection of L-glutamine metabolism in vitro embryo culture.
A surface plasmon resonance (SPR) optical fiber sensor with multimode-coreless-multimode (MNM) structure was developed, which modified by L-glutamine-binding protein (QBP) for detection of L-glutamine (Gln). The QBP was immobilized on the surface of gold films by chemical cross-linking and exhibited a binding affinity for L-glutamine. The conformation of QBP can be changed from the "open" to the "closed", which led to a red-shift of the SPR peak when QBP bounded to L-glutamine. There was a good linear correlation between is a dependence of the SPR peak on and the concentration of L-glutamine concentration in the range 10-100 μM, with a sensitivity of 10.797nm/log10[Gln] for L-glutamine in the in vitro embryo culture (IVC) medium environment, and the limit of detection (LOD) is 1.187 μM. This QBP-modified MNM structure optical fiber SPR sensor provides a new idea for the developmental potential assessment of embryos in the process of in vitro embryo culture.


[Occupational activity and work disability in pregnancy].
From 600 employed pregnant women at least 61% have got a certificate of disablement one time in their pregnancy. 22.4 days of deficiency due in capability of working have been calculated on an average per employed gravida with statistically significant differences with regard to the degree of qualification and the working sphere of these women, too. Combined with an increase in the degree of qualification, a rising amount of days of deficiency has been found (18.5 days in the group of unskilled workers and 30.9 days in the group of pregnant women with high school graduation). The percentage of disablement also clearly varies in the working sphere of gravidae (53.3% in the administration and 71.4% in the public health service). This investigation is a pilot study and will be enlarged and completed later on.


IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling.
In atopic subjects food ingestion drives the production of IgE antibodies that can trigger hypersensitivity reactions. The IL-4 pathway plays a critical role in this response, and genetic polymorphisms in its components have been linked to allergy. We sought to test whether an activating mutation in the IL-4 receptor (IL-4R) α chain enhances allergic responses to a food antigen. F709 mice, in which the IL-4Rα immunoreceptor tyrosine-based inhibitory motif is inactivated, were gavage fed with ovalbumin (OVA). Reactions to OVA challenge and immune responses, including antibody production and T(H)2 responses, were assessed. F709 mice, but not wild-type control animals, sensitized by means of gavage with OVA and either cholera toxin or staphylococcal enterotoxin B, displayed mast cell activation and systemic anaphylaxis on enteral challenge. Anaphylaxis was elicited even in F709 mice enterally sensitized with OVA alone. Bone marrow chimera experiments established that the increased sensitivity conferred by the F709 genotype was mediated mostly by hematopoietic cells but that nonhematopoietic cells also contributed. F709 mice exhibited increased intestinal permeability to macromolecules. The F709 genotype conferred increased OVA-specific IgE but not IgG1 responses, local and systemic T(H)2 responses, and intestinal mast cell hyperplasia compared with wild-type mice. Anaphylaxis was abrogated in F709 mice lacking IgE or the high-affinity receptor for IgE (FcεRI). Augmented IL-4Rα signaling confers increased intestinal permeability and dramatically enhanced sensitivity to food allergens. Unlike anaphylaxis to injected antigens, which in rodents can be mediated by either IgE or IgG antibodies, the food-induced response in F709 mice is solely IgE dependent.


Number of strides required for reliable measurements of pace, rhythm and variability parameters of gait during normal and dual task walking in older individuals.
The reliability with which spatiotemporal gait parameters are measured has neither been well-established for variability parameters nor during dual task walking. The purpose of this study was to examine test-retest reliability of three gait parameters representing pace, rhythm and variability in healthy older persons during normal and dual task walking and to determine the number of strides necessary to measure the parameters reliably. Twenty-four healthy adults aged 65 or older participated in the study. Subjects walked during normal and dual task (backward spelling) walking conditions at self-selected speeds and then repeated the tests. Velocity, cadence and variability in stride velocity were measured with GAITRite instrumentation. Intraclass correlation coefficients (ICCs) were calculated and the numbers of strides required to meet desired magnitudes of reliability were estimated with the Spearman-Brown prophecy formula. ICCs for velocity and cadence were high (>0.841) during normal and dual task walking, indicating strong test-retest reliability. Test-retest reliability for variability in stride velocity was moderate (ICC=0.656) in normal walking and poor (ICC=0.226) in dual task walking. While data collected from fewer than 10 to 20 strides may reliably measure velocity and cadence in either normal or dual task walking, measuring variability in stride velocity reliably may require that data be collected from hundreds of strides, particularly in dual task walking.


Vigilance: the essence of nursing.
Nursing, perhaps more than any other health care profession, claims caring as fundamental to its practice. Professional vigilance is the essence of caring in nursing. This article uses historical and theoretical bases to define professional vigilance and discuss its components. Two types of nursing diagnoses, central and surveillance, are proposed. Central diagnoses indicate the need for the nurse to plan and implement interventions for the achievement of outcomes. North American Nursing Diagnosis Association (NANDA)-approved diagnoses fall in this category. Surveillance diagnoses are those that recognize patient risks that are anticipated by the nurse, who remains ready to act in the event of occurrence. The profession, as a whole, and language developers, in particular, need to expand standardized nursing diagnosis terminology so that the contribution of nurses' vigilance to patient safety may be effectively communicated and documented.


Effect of bioactive tannoid principles of Emblica officinalis on ischemia-reperfusion-induced oxidative stress in rat heart.
The tannoid principles of the fruits of Emblica officinalis have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin-A (37%) and -B (33%) enriched fraction of fresh juice of Emblica fruits (EOT) was investigated for antioxidant activity against ischemia-reperfusion (IRI)-induced oxidative stress in rat heart. Vitamin E (VE) was used as the standard antioxidant agent. IRI was induced in isolated rat heart by perfusing it with modified Kreb-Hensleitt's solution for 5 min, followed by a period of ischemia (stoppage of perfusion) for 10 min and then restoring the perfusion (reperfusion) for 15 min. IRI induced a significant decrease in the activities of cardiac superoxide dismutase, catalase and glutathione peroxidase, with a concomitant increase in lipid peroxidation. These IRI-induced effects were prevented by the administration of EOT (50 and 100 mg/kg body wt.) and VE (200 mg/kg body wt.) given orally twice daily for 14 days prior to the sacrifice of the animals and initiation of the perfusion experiments. The study confirms the antioxidant effect of E. officinalis and indicates that the fruits of the plant may have a cardioprotective effect.


[Leg lengthening using callotasis. I. History of lengthening of extremities and surgical technics].
In the first part of the article divided into two sections the authors describe the history of approaches to limb length discrepancy and they compare several methods and discuss their advantages and disadvantages. The surgical method proper used at the clinic is described incl. preoperative preparation and deliberations as used at the clinic up to the procedure used for removing the fixator after completion of the lengthening of long bones. The operation proper is described in detail from application of the apparatus to performance of osteotomy. The lengthening process is also described.


A time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) activity.
A novel time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) was developed. We used a straightforward strategy to modify a known ALK substrate into a peptide biosensor that can accommodate terbium luminescence sensitization upon its phosphorylation by ALK. Since this strategy is generalizable, this high-throughput screening compatible assay serves as an example for development of other kinase assays that employ terbium luminescence as a read-out.


Genetic testing in a cohort of patients with potential epilepsy with myoclonic-atonic seizures.
Epilepsy with myoclonic-atonic seizures (EMAS) accounts for 1-2% of all childhood-onset epilepsies. EMAS has been shown to have an underlying genetic component, however the genetics of this disorder is not yet well understood. The purpose of this study was to review genetic testing results for a cohort of EMAS patients. A retrospective chart review was conducted for 77 patients evaluated at Children's Hospital Colorado with a potential diagnosis of EMAS. Genetic testing and biochemical testing was reviewed. Family history data was also collected. Seventy-seven percent of the cohort had at least one genetic test performed, and a molecular diagnosis was reached for six patients. Thirty-seven patients had a microarray, six of which identified a copy number variant. Only one was felt to contribute to the phenotype (2p16.3 deletion including NRXN1). Fifty-one patients had an epilepsy panel, two of which were positive (likely pathogenic variant in SCN1A, pathogenic variant in GABRG2). Of the six patients who had whole exome sequencing, two were negative, three were positive or likely positive, and one had multiple variants not felt to explain the phenotype. While EMAS is widely accepted to have a strong genetic component, the diagnostic yield of genetic testing remains low. This may be because several genes now thought to be associated with EMAS are not included on the more commonly ordered epilepsy panels, or have only recently been added to them.


Biological effect of lead-212 localized in the nucleus of mammalian cells: role of recoil energy in the radiotoxicity of internal alpha-particle emitters.
The radiochemical dipyrrolidinedithiocarbamato-212Pb(II) [212Pb(PDC)2] is synthesized and its effects on colony formation in cultured Chinese hamster V79 cells are investigated. The cellular uptake, biological retention, subcellular distribution and cytotoxicity of the radiocompound are determined. The 212Pb is taken up quickly by the cells, reaching saturation levels in 1.25 h. When the cells are washed, the intracellular activity is retained with a biological half-life of 11.6 h. Gamma-ray spectroscopy indicates that the 212Pb daughters (212Bi, 212Po and 208Tl) are in secular equilibrium within the cell. About 72% of the cellular activity localizes in the cell nucleus, of which 35% is bound specifically to nuclear DNA. The mean cellular uptake required to achieve 37% survival is 0.35 mBq of 212Pb per cell, which delivers a dose of 1.0 Gy to the cell nucleus when the recoil energy of 212Bi and 212Po decays is ignored and 1.7 Gy when recoil is included. The corresponding RBE values compared to acute external 137Cs gamma rays at 37% survival are 4.0 and 2.3, respectively. The chemical Pb(PDC)2 is not chemotoxic at the concentrations used in this study. Because the beta-particle emitter 212Pb decays to the alpha-particle-emitting daughters 212Bi and 212Po, these studies provide information on the biological effects of alpha-particle decays that occur in the cell nucleus. Our earlier studies with cells of the same cell line using 210Po (emits 5.3 MeV alpha particle) localized predominantly in the cytoplasm resulted in an RBE of 6. These earlier results for 210Po, along with the present results for 212Pb, suggest that the recoil energy associated with the 212Bi and 212Po daughter nuclei plays little or no role in imparting biological damage to critical targets in the cell nucleus.


Hopelessness, depression, suicidal ideation, and clinical diagnosis of depression.
The relevance of a clinical diagnosis of depression for explaining the discrepant relationships of hopelessness and depression with suicidal ideation was studied. The Beck Depression Inventory (BDI), Hopelessness Scale (BHS), and the Scale for Suicide Ideation (SSI) were administered to 1,306 (72.8%) patients with at least one DSM-III-R mood disorder and 488 (27.3%) patients without any mood disorders. A multiple regression analysis was conducted, and hopelessness was 1.3 times more important than depression was for explaining suicidal ideation. The interactions of the BDI and BHS with diagnostic group were not significant.


[Long association tracts of the human white matter: an analysis of 18 hemisphere dissections and in vivo HARDI-CSD tractography].
Anatomy of the conduction tracts of the cerebral cortex has been studied for a long time. Invention of diffusion tensor tractography renewed interest in this subject. The objectives of this work were to develop and improve protocols for dissection of the long association tracts of the human brain with studying the features of their segmentation, topography, and variability, compare the obtained data with the MR tractography data, and prepare for further clinical and anatomical studies. We used 18 cerebral hemispheres (from 10 males and 8 females; 9 left and 9 right hemispheres). The mean age of cadavers was 68 years. Specimen were fixated in accordance with the Klingler technique. Immediately after collection, specimens were placed in a 10% formalin solution for at least 4 weeks. After that, the pia was removed; specimens were frozen at -20 °C for a week and then unfrozen in a 96% ethanol solution for a day. We performed 10 lateral dissections, 2 lateral dissections with isolation of the frontal aslant tract, 2 basal dissections, 1 combined basolateral dissection, 2 frontal dissections, and 1 medial dissection. At the time of dissection and after it, specimens were stored in a 96% ethanol solution. Modified, disposable, therapeutic wooden spatulas were used for manipulations. A microscope (magnification of 6-40x) was used in 2 lateral and 2 basal dissections. MR tractography (HARDI-CSD) was carried out in 5 healthy volunteers using a GE Signa HDxt MRI scanner a field strength of 3.0 T. We clearly identified the following fascicles: the arcuate fascicle (AF) and superior longitudinal fascicle (SLF) in 6/6 hemispheres on the right and in 5/6 hemispheres on the left, the inferior longitudinal fascicle (ILF) in 3/6 hemispheres on the left and in 4/6 hemispheres on the right, the uncinate fascicle (UF) in 4/4 hemispheres on the left and in 4/4 hemispheres on the right, and the inferior fronto-occipital fascicle (IFOF) in 4/4 hemispheres on the left and in 3/4 hemispheres on the right. Identification was less successful in the case of the frontal aslant tract (FAT) in 1/2 hemispheres on the left and in 0/2 hemispheres on the right. The used technique failed to identify the vertical occipital fascicle (VOF) of Wernicke, a segment of the superior longitudinal fascicle SLF I, and the middle longitudinal fascicle (MdLF). The MR tractography HARDI-CSD data were compared with the dissection data. We described in detail segmentation of the superior longitudinal, arcuate, and inferior fronto-occipital fascicles. Contradictory data were obtained for the superior longitudinal fascicle: a two-segment structure (SLFh and SLFv) was found in most (10/12) specimens, while a three-segment structure was revealed in the other (2/12) specimens (identified SLF II and SLF III). In the arcuate fascicle, the ventral and dorsal segments were successfully identified in 2/12 cases (1 left and 1 right), whereas identification failed in the other cases. During dissection of the inferior fronto-occipital fascicle, we could identify its surface layer in 1 of 8 cases (left) and its deep layer in one more case (left). Examination of the long association tracts using the Klingler technique has significant limitations in the fiber intersection areas (sagittal striatum). The frontal aslant tract was least studied; we proposed a special anterior dissection technique for its isolation. The superior longitudinal fascicle can have both the two-segment (10/12) and three-segment (2/12) structure. Investigation of the segmental anatomy of the long association tracts will be continued in further dissections. When planning neurosurgical interventions in the projection areas of the long association tracts, both preoperative HARDI-tractography and anatomical dissections ex vivo, based on the proposed protocols, can be recommended for the operating surgeon to master a three-dimensional picture of the tract topography.


The role of spatial frequency in expert object recognition.
Novices recognize objects at the basic-category level (e.g., dog, chair, and bird) at which identification is based on the global form of the objects (Rosch, Mervis, Gray, Johnson, & Boyes-Braem, 1976). In contrast, experts recognize objects within their domain of expertise at the subordinate level (e.g., Sparrow or Finch) for which the internal object information may play an important role in identification (Tanaka & Taylor, 1991). To investigate whether expert recognition relies on internal object information, we band-pass filtered bird images over a range of spatial frequencies (SF) and then masked the filtered image to preserve its global form. In Experiment 1, bird experts categorized common birds at the family level (e.g., Robin or Sparrow) more quickly and more accurately than novices. Both experts and novices were more accurate when bird images contained the internal information represented by a middle range of SFs, and this finding was characterized by a quadratic function in which accuracy decreased toward each end of the SF spectrum. However, the experts, but not the novices, showed a similar quadratic relationship between response times and SF range. In Experiment 2, experts categorized Warblers and Finches at the more specific, species level (e.g., Wilson's Warbler or House Finch). Recognition was again fastest and most accurate for images filtered in the middle range of SFs. Collectively, these results indicate that a midrange of SFs contain crucial information for subordinate recognition, and that extensive perceptual experience can influence the efficiency with which this information is utilized. (PsycINFO Database Record


Item response theory analysis of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised in the Pooled Resource Open-Access ALS Clinical Trials Database.
Our objective was to examine dimensionality and item-level performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) across time using classical and modern test theory approaches. Confirmatory factor analysis (CFA) and Item Response Theory (IRT) analyses were conducted using data from patients with amyotrophic lateral sclerosis (ALS) Pooled Resources Open-Access ALS Clinical Trials (PRO-ACT) database with complete ALSFRS-R data (n = 888) at three time-points (Time 0, Time 1 (6-months), Time 2 (1-year)). Results demonstrated that in this population of 888 patients, mean age was 54.6 years, 64.4% were male, and 93.7% were Caucasian. The CFA supported a 4* individual-domain structure (bulbar, gross motor, fine motor, and respiratory domains). IRT analysis within each domain revealed misfitting items and overlapping item response category thresholds at all time-points, particularly in the gross motor and respiratory domain items. Results indicate that many of the items of the ALSFRS-R may sub-optimally distinguish among varying levels of disability assessed by each domain, particularly in patients with less severe disability. Measure performance improved across time as patient disability severity increased. In conclusion, modifications to select ALSFRS-R items may improve the instrument's specificity to disability level and sensitivity to treatment effects.


THE EVOLUTION OF GENETIC CORRELATIONS: AN ANALYSIS OF PATTERNS.
The genetic correlation is a central parameter of quantitative genetics, providing a measure of the rate at which traits respond to indirect selection (i.e., selection that does not act upon the traits under study, but some other trait with which they have genes in common). In this paper, I review the pattern of variation among four combinations of traits: life history × life history (L × L), morphological × morphological (M × M), life history × morphological (L × M), and behavioral × behavioral (B × B). A few other combinations were investigated, but insufficient data were obtained for separate analysis. A total of 1798 correlations, distributed over 51 different animal and plant species, were analyzed. The analysis was conducted at two levels: first by dividing the data set solely by trait combination, and second by blocking the data by trait combination and species. Because selection will tend to fix alleles that show positive correlations with fitness traits faster than those that are negative and because the latter are expected to arise more frequently by mutation, correlations between life-history traits are predicted to be more often negative than those between morphological traits. This prediction was supported, with the ranking in decreasing proportion of negative correlations being: L × L > L × M > B × B > M × M. The mean magnitude of the genetic correlation shows little variation among morphological and life-history combinations, and the distribution of values is remarkably flat. However, the estimated standard errors and the coefficient of variation (SE/rG ) are large, making it difficult to separate biological factors influencing the pattern of dispersion from experimental error. Analysis of the phenotypic and genetic correlations suggest that for the combinations M × M and L × M, but not L × L or B × B, the phenotypic correlation is an adequate estimate of the genetic correlation.


Behavioural effects of genetically engineered cells releasing dopa and dopamine after intracerebral grafting in a rat model of Parkinson's disease.
The relative importance of synaptic versus paracrine dopamine transmission for the occurrence of functional effects following intrastriatal grafting is not fully established. In the present study we grafted cell lines, expressing the form I of human tyrosine hydroxylase after infection with a recombinant retrovirus and selection in tyrosine-free-medium, to the denervated striatum in order to analyse the extent to which extracellular dopamine levels can be restored and the effect of a diffuse release of dopamine on motor impairement in a rat model of Parkinson's disease. In petri dish, the modified fibroblast cells (NIH.3T3) release DOPA constitutively whereas the modified endocrine cells (RIN) store and release dopamine in a regulated way. Interestingly, in denervated striatum, grafts of modified fibroblast cells produce DOPA which was efficiently converted into dopamine by the host striatal tissue. In the grafted striatum, both fibroblast and endocrine cells restore subnormal levels of diffuse release of dopamine which is notably unaffected and stimulated, respectively, by high concentration of potassium, in connection with the in vitro properties of the grafted cells. The intrastriatal grafts of modified cells partially reversed the apomorphine-induced but not the amphetamine-induced motor asymmetry. We discuss the implications of these results in the context of Parkinson disease.


Sequence determinants of cytosolic N-terminal protein processing.
N-terminal methionine removal has been analyzed statistically in a large sample of prokaryotic and eukaryotic cytosolic proteins in an attempt to uncover common sequence determinants. We find that the residue next to the initiator Met is the most important determinant of N-terminal processing: Lys, Arg, Leu and (in prokaryotes) Phe and Ile protect the initiator Met from being removed when next to it in the sequence; Ala, Gly, Pro, Ser, Thr and (in eukaryotes) Val in this position cause its removal. Subsequent acetylation is confirmed to be strongly biased towards Ala, Met and Ser residues; when Met is acetylated, Asp is the predominant penultimate residue in eukaryotes. Also, we find major differences in the relative abundance of the various residues next to the initiator Met between prokaryotes and eukaryotes: prokaryotic proteins are much more biased towards Lys as the Met-protecting residue, and towards Ala when met is to be removed, than eukaryotic ones. Finally, we show that our results can explain a part of the mRNA 'consensus sequence' found around eukaryotic initiator AUG codons.


Heterogeneity of Circulating Tumor Cells in Neoadjuvant Chemotherapy of Breast Cancer.
The biological properties of circulating tumor cells (CTCs), and their dynamics during neoadjuvant chemotherapy are important, both for disease progression prediction and therapeutic target determination, with the aim of preventing disease progression. The aim of our study was to estimate of different CTC subsets in breast cancer during the NACT (neoadjuvant chemotherapy). The prospective study includes 27 patients with invasive breast cancer, T2-4N0-3M0, aged 32 to 60 years. Venous heparinized blood samples, taken before and after biopsy, after each courses of chemotherapy (on days 3-7), and before surgical intervention, served as the material for this study. Different subsets of circulating tumor cells were determined on the basis of the expression of EpCAM, CD45, CD44, CD24, and N-Cadherin using flow cytometry. As the result of this study, it has been observed that significant changes in the quantity of the different subsets of circulating tumor cells in patients' blood were observed after carrying out the 3rd course of NACT. NACT causes significant changes in the quantity of six CTC subsets, with various combinations of stemness and epithelial-mesenchymal transition (EMT) properties.


Bilateral purely laparoscopic nephrectomy for renal masses using five ports without repositioning: a case report.
Bilateral nephrectomy is an infrequently performed procedure. The indications include bilateral masses too large for nephron-sparing surgery, recalcitrant hypertension in dialysis patients, pain, infection, reflux, or large symptomatic polycystic kidneys. Bilateral pretransplant purely laparoscopic nephrectomy for bilateral renal masses has not been reported previously. We present our experience with this procedure using five transabdominal trocars without having to reposition the patient. We employed a five-port technique in a middle-aged woman with end-stage renal disease who presented with an infected peritoneal dialysis catheter. On abdominal CT, she had bilateral enhancing renal masses. Six weeks after removal of the catheter, she underwent bilateral transperitoneal laparoscopic nephrectomy. The technique is described, and recommendations are made regarding potential obstacles. The procedure was performed in 185 minutes, and the total hospital time was 41 hours. The estimated blood loss was 50 mL. Final pathology examination revealed a 5.5-cm right renal-cell carcinoma stage T1N0M0 and left hydronephrosis, atrophy, nephrosclerosis, and thick-walled renal cysts without malignancy. On 3-month follow-up she is well, without complaints. Bilateral pretransplant purely laparoscopic nephrectomy can be performed without significant repositioning, redraping, and resterilization. In this case, operative time and cosmesis were acceptable, and surgical morbidity was low.


A patient with fulminant influenza-related bacterial pneumonia due to Streptococcus pneumoniae followed by Mycobacterium tuberculosis infection.
A 74-year-old man with poorly controlled diabetes mellitus was admitted to our hospital because of severe respiratory disturbance, fever, and sputum. We found massive consolidation of the right lung and nodular shadows on the left lung on chest X-ray, and detected influenza virus and Streptococcus pneumoniae antigen from a nasopharyngeal swab and urine sample, respectively. Co-infection with influenza virus and bacteria was suspected, and oseltamivir and biapenem were prescribed. Laboratory data improved after the addition of sivelestat sodium hydrate, an inhibitor of neutrophil-derived elastase; however, chest X-ray findings became worse on Day 8, and we administered 1 g methylprednisolone intravenously for two days. On Day 12, we detected Mycobacterium tuberculosis in the sputum, even though we did not previously detect any acid-fast bacilli, and started anti-tuberculosis drugs, such as isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide; however, the patient died 12 days later. Severe influenza-related bacterial pneumonia with Streptococcus pneumoniae and subsequently secondary tuberculosis infection were finally suspected in this case. This was a very rare case in which additional tuberculosis infection was found in a patient with fulminant pneumonia due to co-infection of influenza virus and bacteria. It is necessary to observe patients with influenza carefully, especially when steroids are used, even if antibiotics are also administered.


Antioxidative effect of quercetin and its equimolar mixtures with phenyltin compounds on liposome membranes.
Our earlier studies have shown that the compounds diphenyltin dichloride (DPhT) and triphenyltin chloride (TPhT) in the presence of UVC radiation enhanced the degree of phosphatidylcholine liposome membrane oxidation (J. Agric. Food Chem. 2005, 53, 76-83). The prooxidative behavior of the compounds has now been confirmed with the electron paramagnetic resonance method, which proved the possibility that the studied compounds can exist in free radical forms. The present work investigates the possibility of the protective action of quercetin on phosphatidylcholine liposome membranes exposed to the prooxidative action of DPhT and TPhT induced by UV radiation (lambda = 253.7 nm). The concentrations of quercetin and its equimolar mixtures with DPhT and TPhT were determined (and compared with well-known antioxidants as standards-trolox and butylated hydroxytoluene, also in the presence of phenyltins) as those that induce 50% inhibition in oxidation of liposomes radiated with UV. They are 5.1 +/- 0.10, 2.9 +/- 0.12, and 1.9 +/- 0.08 microM (differences between the values are statistically significant), constituting the following sequence of antioxidative activity: quercetin:TPhT > quercetin:DPhT > quercetin. This relation is confirmed by the results on the antiradical ability of quercetin and its mixtures with DPhT and TPhT toward the free radical 1,1-diphenyl-2-pricrylhydrazil. Similar sequences obtained in both studies suggest a possible mechanism of the antiradical action of the mixtures as free radical scavengers. We suggested that (i) quercetin's ability, documented by spectrophotometric, infrared attenuated total reflectance spectroscopy, (1)H NMR, and molecular modeling methods, to form complexes with phenyltins indicates a possible way of protection against the peroxidation caused by the free radical forms of phenyltins and (ii) the differentiation in the action of the quercetin/TPhT and quercetin/DPhT associates (statisticaly significant) may result from a different localization in the liposome membrane, which is indicated by the results of the fluorimetric studies.


Balancing losses and growth: a relational perspective on identity formation in the second half of life.
Psychoanalysis has so far only to a limited extent examined specifically grown-up and mature organizations of the self. The Freudian contributions mainly examine the impact of losses on the second half of life. The Eriksonian approaches put greater emphasis of possible gains and adaptation, while less attention is paid to inner, subjective life. In contrast, the Jungian and transpersonal views emphasize possible increase in inner freedom and a more relativistic, holistic, and possibly spiritual or "worldcentric" view on existence. Within a relational psychoanalytic perspective on identity formation in the second half of life, these possible changes may be described as a mature widening of potential space, using Winnicott's terms. Relationships also may be more based on "being" than "doing." A perspective incorporating potentials for increased experiential depth and creativity must include attention to actual losses and suffering, conflicts involved in letting go of certain ambitions, and lifelong themes that may be actualized.


Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.
The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.


Study of the influence of crossbite on the size of the apical area in a child population by analyzing panoramic X-ray.
The apical area is the space in the maxillary bones that contains teeth during formation and is subsequently occupied by the apices of the permanent teeth. Its dimensions are easy to perceive and determine by observing a panoramic X-ray. Our objective was to analyze the influence of crossbite on the size of the anterior and mesial apical area in Caucasian children. Based on the ortopantomograph of 353 patients in mixed dentition and crossbite, the sizes of the apical areas of the four hemiarches were studied using the Tps Dig Version 2® computer program. These data were subjected to statistical analysis using the SPSS 22.0 for Windows program and applying the methods of descriptive statistics of quantitative variables, the Kolmogorov-Smirnov test, the non-parametric test Mann-Whitney-Wilcoxon test, and the paired Student t-test. In the group of boys, average values in the superior-mesial, superior-anterior, inferior-mesial and inferior-anterior apical areas of the crossbite were 173.43, 99.85, 180.32 and 87.56 respectively, with the lower values being in the hemiarch without malocclusion. In the group of girls, for the same apical areas, average values were 165.64, 94.24, 168.62 and 83.34 respectively, with all the highest values being in the hemiarch with crossbite, except for the inferior-mesial apical area. Statistically significant differences were found in the hemiarch with crossbite between both genders in the superior-anterior, inferior-anterior and inferior-mesial apical areas, with the significance being 0.001, 0.029 and 0.001 respectively, while in the hemiarch without malocclusion significance was observed in the superior-mesial, superior-anterior and inferior-mesial apical areas, with values of 0.004, 0.001 and 0.004, respectively. Crossbite affects the size of the anterior apical area in both arches and in both genders. The mesial apical area is influenced by this malocclusion in the jaw in boys and in the maxilla girls. Key words:Apical area, ortopantomography, crossbite.


Complications, effects on dialysis dose, and survival of tunneled femoral dialysis catheters in acute renal failure.
Availability of a functional vascular access is a mandatory prerequisite for extracorporeal renal replacement therapy in patients with acute renal failure. The femoral site of insertion commonly is chosen because it is an easy and convenient access. However, an array of complications may substantially alter the quality of treatment, and it appears that catheter-related morbidity and dysfunction are more frequent with the femoral than internal jugular site. This study is designed to evaluate the potential benefits of using soft silicone tunneled catheters ((ST)Caths) at the femoral site. Thirty patients with acute renal failure treated by intermittent hemodialysis (IHD) and/or continuous venovenous hemodiafiltration (CVVHDF) were assigned to either twin (ST)Caths or twin polyurethane nontunneled femoral catheters. Time necessary for catheter insertion, catheter-related complications, and catheter lifespan were monitored. Catheter performance during IHD and the effect of catheter type on dialysis dose were evaluated. The time necessary for (ST)Cath insertion was significantly longer. The incidence of vein thrombosis and catheter-related infection was lower, and the ratio of venous return pressure to catheter blood flow was better with an (ST)Cath. Recirculation rates were similar for both types of catheters. Whether treated by using IHD or CVVHDF, patients with an (ST)Cath benefited from a greater delivered dialysis dose. Multivariate analysis confirmed that (ST)Cath use was a determinant factor to optimize dialysis dose delivery. (ST)Cath patency was significantly longer. In patients with acute renal failure, use of an (ST)Cath minimizes catheter-related morbidity and improves dialysis efficiency compared with conventional femoral catheters.


Assessing therapeutic response non-invasively in a neonatal rat model of acute inflammatory white matter injury using high-field MRI.
Perinatal infection and inflammatory episodes in preterm infants are associated with diffuse white matter injury (WMI) and adverse neurological outcomes. Inflammation-induced WMI was previously shown to be linked with later hippocampal atrophy as well as learning and memory impairments in preterm infants. Early evaluation of injury load and therapeutic response with non-invasive tools such as multimodal magnetic resonance imaging (MRI) would greatly improve the search of new therapeutic approaches in preterm infants. Our aim was to evaluate the potential of multimodal MRI to detect the response of interleukin-1 receptor antagonist (IL-1Ra) treatment, known for its neuroprotective properties, during the acute phase of injury on a model of neonatal WMI. Rat pups at postnatal day 3 (P3) received intracerebral injection of lipopolysaccharide with systemic IL-1Ra therapy. 24 h later (P4), rats were imaged with multimodal MRI to assess microstructure by diffusion tensor imaging (DTI) and neurochemical profile of the hippocampus with 1H-magnetic resonance spectroscopy. Astrocyte and microglial activation, apoptosis and the mRNA expression of pro-inflammatory and necroptotic markers were assessed. During the acute phase of injury, neonatal LPS exposure altered the concentration of hippocampus metabolites related to neuronal integrity, neurotransmission and membrane integrity and induced diffusivity restriction. Just 24 h after initiation of therapy, early indication of IL-1Ra neuroprotective effect could be detected in vivo by non-invasive spectroscopy and DTI, and confirmed with immunohistochemical evaluation and mRNA expression of inflammatory markers and cell death. In conclusion, multimodal MRI, particularly DTI, can detect not only injury but also the acute therapeutic effect of IL-1Ra suggesting that MRI could be a useful non-invasive tool to follow, at early time points, the therapeutic response in preterm infants.


Development of a dual-flow tissue perfusion device for modeling the gastrointestinal tract-brain axis.
Despite the large number of microfluidic devices that have been described over the past decade for the study of tissues and organs, few have become widely adopted. There are many reasons for this lack of adoption, primarily that devices are constructed for a single purpose or because they are highly complex and require relatively expensive investment in facilities and training. Here, we describe a microphysiological system (MPS) that is simple to use and provides fluid channels above and below cells, or tissue biopsies, maintained on a disposable, poly(methyl methacrylate), carrier held between polycarbonate outer plates. All other fittings are standard Luer sizes for ease of adoption. The carrier can be coated with cells on both sides to generate membrane barriers, and the devices can be established in series to allow medium to flow from one cell layer to another. Furthermore, the carrier containing cells can be easily removed after treatment on the device and the cells can be visualized or recovered for additional off-chip analysis. A 0.4 μm membrane with cell monolayers proved most effective in maintaining separate fluid flows, allowing apical and basal surfaces to be perfused independently. A panel of different cell lines (Caco-2, HT29-MTX-E12, SH-SY5Y, and HUVEC) were successfully maintained in the MPS for up to 7 days, either alone or on devices connected in series. The presence of tight junctions and mucin was expressed as expected by Caco-2 and HT-29-MTX-E12, with Concanavalin A showing uniform staining. Addition of Annexin V and PI showed viability of these cells to be >80% at 7 days. Bacterial extracellular vesicles (BEVs) produced by Bacteroides thetaiotaomicron and labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbo-cyanine perchlorate (DiD) were used as a model component of the human colonic microbiota and were visualized translocating from an apical surface containing Caco-2 cells to differentiated SH-SY5Y neuronal cells cultured on the basal surface of connected devices. The newly described MPS can be easily adapted, by changing the carrier to maintain spheroids, pieces, or slices of biopsy tissue and joined in series to study a variety of cell and tissue processes. The cell layers can be made more complex through the addition of multiple cell types and/or different patterning of extracellular matrix and the ability to culture cells adjacent to one another to allow study of cell:cell transfer, e.g., passive or active drug transfer, virus or bacterial entry or BEV uptake and transfer.


Mechanical properties' improvement of a tricalcium phosphate scaffold with poly-l-lactic acid in selective laser sintering.
To improve the mechanical properties of a scaffold fabricated via selective laser sintering (SLS), a small amount (0.5-3 wt%) of poly-l-lactic acid (PLLA) is added to the β-tricalcium phosphate (β-TCP) powder. The fracture toughness of the scaffold prepared with the mixture powder containing 1 wt% PLLA increases by 18.18% and the compressive strength increases by 4.45% compared to the scaffold prepared from the β-TCP powder. The strengthening and toughening is related to the enhancement of β-TCP sintering characteristics via introducing a transient liquid phase in SLS. Moreover, the microcracks caused by the volume expansion due to the β-α phase transformation of TCP are reduced because of the PLLA inhibition function on the phase transformation. However, PLLA additive above 1 wt% would lead to a PLLA residue which will decrease the mechanical properties. The experimental results show that PLLA is an effective sintering aid to improve the mechanical properties of a TCP scaffold.


Pharmacokinetics, pharmacodynamics, and treatment issues of benzodiazepines: alprazolam, adinazolam, and clonazepam.
Alprazolam, adinazolam, and clonazepam share the typical pharmacological effects of benzodiazepines yet are diverse in their pharmacokinetic properties. Alprazolam has an average terminal elimination half-life of 12 hours, whereas adinazolam generates a metabolite responsible for its benzodiazepine effects whose half-life is less than 3 hours. Clonazepam shows a much slower elimination with a half-life of 20 to 80 hours. The rate of decline of plasma benzodiazepine concentration may be an important factor in determining the number of daily doses necessary to maintain optimal anti-panic effects and to minimize rebound anxiety and withdrawal effects. Clonazepam, which has a longer half-life, would be expected to have some advantages over the other drugs. The limited data available do not provide evidence for any substantial advantages of one benzodiazepine over another. The potential disadvantage of the rapid elimination half-life of adinazolam and its metabolite may be offset by formulation in a sustained release capsule. When discontinuing therapy abruptly, a benzodiazepine with a longer half-life may be advantageous; however, when pharmacotherapy is discontinued gradually, the importance of half-life is diminished. Studies of the pharmacodynamics of drug-receptor interactions suggest new approaches to minimizing the adverse effects of discontinuing benzodiazepine therapy. Preliminary data relating plasma alprazolam concentrations to anxiolytic and adverse effects are presented.


Effect of acute and chronic administration of clonidine on hypothalamic content of growth hormone-releasing hormone and somatostatin in the rat.
Hypothalamic GH-releasing hormone (GHRH) and somatostatin contents were determined in male rats at pre- and mid-pubertal stages following acute (0.15 mg/kg) or chronic (0.1 mg/kg twice daily for 7 days) administration of clonidine. Hypothalamic GHRH content increased markedly during transition from pre- to mid- and late-pubertal stages (2.05 +/- 0.17 vs 3.13 +/- 0.26 and 3.46 +/- 0.20 ng/hypothalamus respectively, means +/- S.E.M.). Hypothalamic GHRH content was markedly decreased 1 h after clonidine administration in mid-pubertal but not in prepubertal rats (3.67 +/- 0.23 vs 2.65 +/- 0.22 ng/hypothalamus). Hypothalamic somatostatin content, on the other hand, decreased in both age groups, although the decrease in the mid-pubertal group was more pronounced (51% and 38% respectively). In addition, the GH responsiveness to clonidine was higher at mid-puberty than at prepuberty. Determination of hypothalamic somatostatin and GHRH content in the chronic experiment 4 h after the last drug administration revealed a marked decrease in GHRH in the mid-pubertal rats and a slight decrease in the prepubertal rats (1.78 +/- 0.32 vs 3.15 +/- 0.31 and 2.01 +/- 0.30 vs 2.35 +/- 0.15 ng/hypothalamus; P less than 0.005 and P less than 0.05 respectively) whereas somatostatin levels were not altered. It is suggested that the clonidine-induced GH secretion is modulated by a chain of events which involves primary stimulation of GHRH release resulting in increased GH secretion which, via a negative-feedback mechanism, triggers an enhancement of somatostatin release which ultimately normalizes the system. This mechanism is age-dependent and reaches full maturity only at the onset of puberty.


Community-Based Primary Care Management for an Older Adult With COVID-19: A Case Report.
This case report describes occupational therapy services provided in consultation with a primary care practice for a community-dwelling older adult dyad with mild coronavirus disease 2019. The occupational therapy evaluation included administration of the Canadian Occupational Performance Measure through telehealth to identify priority areas for intervention; the clients selected participation during activities of daily living and mealtime, fall prevention, cooking together, and leisure participation. The intervention process focused on addressing the dyad's identified priorities as well as managing caregiver stress and preventing hospitalization. Positive outcomes were achieved while adhering to social distancing guidelines set forth by state and national agencies.


Dynamic-Mechanical and Dielectric Evidence of Long-Lived Mesoscale Organization in Ionic Liquids.
Experimental evidence of the dynamics of mesoscopic structure in room-temperature ionic liquids-a feature expected to correlate with many physicochemical properties of these materials-remains limited. Here, we report the observation of slow, sub-α relaxations corresponding to dynamics of nanoscale hydrophobic aggregates in a systematic series of 1-alkyl-3-methylimidazolium-based ionic liquids from detailed analysis of dynamic-mechanical and broad-band dielectric spectra. The emergence of the sub-α relaxations correlates with increases in the zero-shear viscosity and static dielectric permittivity, constituting direct evidence of the influence of mesoscale aggregation on the physicochemical properties of ionic liquids.


The Intermediate Equivalent Value outpatient procedure scoring system to maximise the workload of local anaesthetic operating theatres.
Time management of local anaesthetic (LA) outpatient lists is usually via arbitrary methods. The East Yorkshire Plastic Surgery Service covers a wide area to supply daily LA lists for adults. Implementation of government targets requires an ever increasing need to assess and improve the efficiency of care. In this environment it is necessary to ensure that quality of care is maintained and it is not suitable to just book a finite number of cases per list. Methods have to be devised to accurately reflect and assess each surgical procedure to maximise workload. The BUPA Intermediate Equivalent Value (IFV) coding system has assigned a numerical score to graded surgical procedures according to their complexity. This coding system has 'minor' and 'intermediate' grades both containing procedures undertaken in the outpatient theatre, but each grade is too broad spectrum to analyse outpatient lists. Data was analysed from 482 plastic surgery LA lists to assess these grades and subdivided them into 11 divisions of procedure complexity. The IEV, represented as a numerical score, was calculated for each of these surgical divisions reflecting their complexity and surgical workload (operative time). All outpatient lists can then be constructed according to the actual workload to be undertaken in each operative list and accordingly should enhance list efficiency and maintain quality.


Biological and environmental predictors of the dysregulation profile in children and adolescents: the story so far.
Most children and adolescents attending mental health services exhibit severe affective and behavioral dysregulation. The dysregulation profile (DP) seems to be an indicator of self-regulatory problems, overall psychopathology, symptom severity, and functional impairment. Although there are studies signaling its importance as a marker of severe psychopathology and long-term impairment, little is known about its predictors. We reviewed the existing literature and found biological and environmental factors associated with the DP. The DP seems to have high heritability rates, blunted hypothalamic-pituitary-adrenal axis responses at stress tasks, and attention problems regardless of emotional context. Some family factors (such as abnormal qualities of upbringing, lower effortful control, parental hostility, and parental substance use disorders) are also related to the DP. More research about specific predictors of the DP is clearly needed. Longitudinal studies would help identify them more clearly.


Heterogeneous susceptibility of circulating SIV isolate capsids to HIV-interacting factors.
Many species of non-human primates in Africa are naturally infected by simian immunodeficiency viruses (SIV) and humans stand at the forefront of exposure to these viruses in Sub-Saharan Africa. Cross-species transmission and adaptation of SIV to humans have given rise to human immunodeficiency viruses (HIV-1 and HIV-2) on twelve accountable, independent occasions. However, the determinants contributing to a simian-to-human lasting transmission are not fully understood. Following entry, viral cores are released into the cytoplasm and become the principal target of host cellular factors. Here, we evaluated cellular factors likely to be involved in potential new SIV cross-species transmissions. We investigated the interactions of capsids from naturally circulating SIV isolates with both HIV-1 restricting (i.e. TRIM5 proteins) and facilitating (i.e. cyclophilin A and nucleopore-associated Nup358/RanBP2 and Nup153) factors in single-round infectivity assays that reproduce early stages of the viral life-cycle. We show that human TRIM5α is unlikely to prevent cross-species transmission of any SIV we tested and observed that the SIV CA-CypA interaction is a widespread but not a universal feature. Moreover, entry in the nucleus of different SIV appeared to follow pathways that do not necessarily recruit Nup358/RanBP2 or Nup153, and this regardless of their interaction with CypA. Nevertheless, we found that, like HIV-1, human-adapted HIV-2 infection was dependent on Nup358/RanBP2 and Nup153 interactions for optimal infection. Furthermore, we found that, unlike HIV CA, SIV CA did not require a direct interaction with the Cyp-like domain of Nup358/RanBP2 to carry out successful infection. Circulating SIV present a variety of phenotypes with regard to CA-interacting restricting or facilitating factors. Altogether, we unveiled unidentified pathways for SIV CA, which could also be exploited by HIV in different cellular contexts, to drive entry into the nucleus. Our findings warrant a closer evaluation of other potential defenses against circulating SIV.