Effect of the Glutamate NMDA Receptor Antagonist Memantine as Adjunctive Treatment in Borderline Personality Disorder: An Exploratory, Randomised, Double-Blind, Placebo-Controlled Trial.
Borderline personality disorder (BPD) is a complex, severe and highly stigmatised psychiatric illness. Several lines of evidence highlight the causal link between chronic stress, glucocorticoid response to stress and glutamatergic overactivity as a key event in the pathophysiology of BPD. Therefore, molecular mechanisms capable of regulating glutamate excitotoxicity represent novel and potentially promising treatment targets. Memantine-HCl is a voltage-dependent N-methyl-D-aspartate (NMDA) receptor 'channel blocker' that selectively blocks pathological glutamate overactivity. The aim of the current study was to determine if memantine can improve BPD symptoms. An 8-week, double-blind, placebo-controlled trial of adjunctive memantine to treatment as usual was conducted. Treatment as usual comprised antidepressants (selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, noradrenergic and specific serotonin antagonists and serotonin noradrenaline reuptake inhibitors), mood stabilisers and antipsychotics, as well as psychotherapy and other psychosocial interventions. Sixteen participants received oral placebo while 17 participants received daily oral memantine 10 mg for 7 days, with subsequent titration to daily oral memantine 20 mg. Eligibility criteria included men and women aged between 16-65 years, with a diagnosis of BPD according to the Diagnostic Interview for Borderline Patients. Primary outcome measures included the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), assessed fortnightly. Secondary measures included an adverse effect questionnaire administered fortnightly to assess adverse effects known to be related to memantine use. According to intention-to-treat, latent growth curve analyses, a significant change in total score of ZAN-BPD symptom severity was observed in the memantine group at 20 mg/daily across time, compared with placebo (p = 0.02). No adverse effects were significantly more frequent among participants receiving active memantine than among those receiving placebo. Memantine at a 20-mg daily dose is a well tolerated drug that can improve BPD symptomatology and may be a promising novel therapeutic for its treatment. Further studies are needed to explore the efficacy of memantine versus placebo, as well as in comparison with other potential treatments for BPD. ClinicalTrials.gov identifier: NCT02097706.


Improved delay-dependent asymptotic stability criteria for delayed neural networks.
This brief is concerned with asymptotic stability of neural networks with uncertain delays. Two types of uncertain delays are considered: one is constant while the other is time varying. The discretized Lyapunov-Krasovskii functional (LKF) method is integrated with the technique of introducing the free-weighting matrix between the terms of the Leibniz-Newton formula. The integrated method leads to the establishment of new delay-dependent sufficient conditions in form of linear matrix inequalities for asymptotic stability of delayed neural networks (DNNs). A numerical simulation study is conducted to demonstrate the obtained theoretical results, which shows their less conservatism than the existing stability criteria.


Atrial fibrillation in a preterm newborn with structurally normal heart.
Atrial fibrillation (AF) is a really uncommon arrhythmia in newborns. Here, we report the case of a 1-day-old infant who was recovered in Neonatal Intensive Care Unit for a twin-to-twin transfusion. The appearance of an unexpected AF was registered at his continuous electrocardiographic monitoring. Both chest X-ray and echocardiographic examination revealed the anomalous insertion of the tip of a central venous catheter (CVC) into the heart ('umbilical artery → inferior vena cava → right atrium → patent foramen ovale → left atrium'). AF ceased as soon as the CVC was extracted from the heart. The mechanical irritation of both atria caused by the malposition of the CVC might be the underlying mechanism responsible for the triggering of AF in this unique case report.


Transition-Metal-Free Direct C-H Arylation of Quinoxalin-2(1H)-ones with Diaryliodonium Salts at Room Temperature.
A method of synthesizing 3-arylquinoxalin-2(1H)-ones using diaryliodonium tetrafluoroborates under mild conditions is described. This protocol has a wide substrate scope and enables direct C-H functionalization. The synthetic potential of this coupling was explored using a range of readily accessible diaryliodonium salts and quinoxalin-2(1H)-ones.


Effect of different doses of recombinant human growth hormone therapy on children with growth hormone deficiency: a retrospective observational study.
The aim of this study was to explore the effects of different doses of recombinant human growth hormone (rhGH) treatment on children with growth hormone deficiency (GHD). Medical records of 174 GHD patients admitted to our hospital from June 2019 to January 2022 were retrospectively evaluated. A total of 136 patients met the inclusion criteria, of which 70 received 0.1 U/ (kg·d) (low-dose group) and 66 received 0.2 U/ (kg·d) dose of rhGH treatment (high-dose group). Growth and development status [height, weight, height standard deviation (HtSDS), growth rate], bone age, bone density, speed of sound (SOS) as distal radius bone mass, biochemical indicators of growth and development [insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3)], growth hormone (GH) levels and incidence of adverse reactions were collected and compared between the two groups before and after one year of the treatment. After the treatment, height, weight, HtSDS, and growth rate of the two groups increased compared to before the treatment and were significantly higher in the high-dose group than in the low-dose group (p<0.05). After one year of treatment, the following observations were made: the bone age of the two groups increased compared to the baseline values and was higher in the high-dose group compared to the low-dose group (p<0.05). The SOS of the two groups decreased but was significantly higher in the high-dose group compared to the low-dose group (p<0.05). Serum levels of IGF-1, IGFBP-3, and GH in both groups increased compared to the baseline values and were higher in the high-dose group than in the low-dose group (p<0.05). There was no significant difference in the incidence of adverse reactions between the high-dose group (8.6%) and the low-dose group (6.1%) (p>0.05). High-dose rhGH treatment for GHD is safe and can more effectively upregulate IGF-1, IGFBP-3, and GH, and promote the growth and development of children.


Comparative essential oil composition and antifungal effect of bitter fennel (Foeniculum vulgare ssp. piperitum) fruit oils obtained during different vegetation.
The chemical composition of the flower and unripe and ripe fruits from fennel (bitter) (Foeniculum vulgare ssp. piperitum) has been examined by gas chromatography and gas chromatography-mass spectrometry. The main identified components of the flower and unripe and ripe fruit oils were estragole (53.08%, 56.11%, and 61.08%), fenchone (13.53%, 19.18%, and 23.46%), and alpha-phellandrene (5.77%, 3.30%, and 0.72%), respectively. Minor qualitative and major quantitative variations for some compounds of essential oils were determined with respect to the different parts of F. vulgare. The oils exerted varying levels of antifungal effects on the experimental mycelial growth of Alternaria alternata, Fusarium oxysporum, and Rhizoctonia solani. The 40 ppm concentrations of fennel oils showed inhibitory effect against mycelial growth of A. alternaria, whereas 10 ppm levels were ineffective. The analyses show that fennel oils exhibited different degrees of fungistatic activity depending on the doses.


Coping in adolescents with cancer: a review of the literature.
The dual challenge of normal adolescent development combined with a diagnosis places high demands on the coping of adolescents with cancer (AWC). A review was conducted to synthesize and critique studies of coping in AWC. Findings from this review indicated inconsistent results for developmental and gender differences as well as associations of coping with distress. A number of limitations were associated with these studies, including the use of small samples, lack of consistency in the conceptualization of coping and instruments, and limited knowledge helpful to inform intervention research to improve effective coping in AWC. Future studies are needed to address these limitations.


Effect of Er:YAG laser on adhesion of root canal sealers.
This in vitro study evaluated the effect of Er:YAG laser on adhesion to human dentin of Grossman, Endomethasone, N-Rickert, and Sealer 26 root canal sealers. The crowns of 40 human molars were cut on the occlusal side until a flat dentin surface was obtained. The teeth were divided into two groups: group 1, no laser application; and group 2, irradiation with Er:YAG laser (KaVo Key Laser 2; 11 mm focal distance, perpendicular to the dentin surface, 4 Hz frequency, 200 mJ energy, 62 J total energy and 313 pulses, 1-min application time, and 2.25 W power). Five samples were tested for each sealer and each group. An Instron universal testing machine was used for the adhesion test. Sealer 26 showed the best adhesion both with and without laser application (p < 0.01). Grossman and N-Rickert sealers had intermediate values, and Endomethasone had the worst adhesion. Application of Er:YAG laser did not alter the adhesion of Grossman, N-Rickert, or Endomethasone sealers. However, laser application increased the adhesion of Sealer 26. The epoxy resin-based root canal sealer (Sealer 26) adhered better to dentin prepared with and without Er:YAG laser than the zinc oxide/eugenol-based sealers (Endomethasone, N-Rickert, and Grossman).


The influence of CLIA '88 on physician office laboratories.
The study objectives were to examine the influence of the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) on laboratory testing activities in physician offices, and to identify relationships between the characteristics of practices and their responses to the regulation. The data come from a 1995 survey of physician office laboratories conducted by Mathematica Policy Research, and are supplemented by data from a 1991 laboratory survey. Primary care physician practices performing level I and level II tests in 1991 were resurveyed in 1995. Respondents were asked a series of questions pertaining to the types of laboratory tests performed in their offices, and whether CLIA '88 had any influence on the decision to change testing practices. We present descriptive statistics to examine differences across practices in response to CLIA '88. Significant determinants of the decision to drop or modify onsite testing activities are identified using multivariate analysis. More than 64% of physicians surveyed cited CLIA '88 as a factor in their decision to reduce or eliminate in-office testing. The most striking effect of CLIA '88 appears to be on pediatric practices and practices in rural areas, of which more than 70% have reduced or eliminated onsite testing. Where the potential burden of compliance is smaller, as in large practices, CLIA '88 has had less impact. CLIA '88 has had significant influence on access to laboratory testing services. According to the data from the 1995 survey, almost two thirds of physicians have eliminated some or all in-office tests. Of those physicians previously conducting in-office tests, 70% have chosen to send patients and specimens to outside facilities, resulting in greater inconvenience for patients and delays in diagnosis and treatment. These delays, and the potential for patient noncompliance stemming from the inconvenience of obtaining tests, have serious implications for the quality of medical care.


Spontaneous postnatal resolution of a cystic lung mass: A case report.
Postnatal cystic adenomatoid malformations (CAMs) are managed by surgical excision. Asymptomatic CAMs have decreased in size with initial observation. This is the first reported case of complete resolution of a postnatal CAM. Premature infants with asymptomatic CAMs may benefit from careful observation as their initial treatment.


Diagnosis of Duchenne Muscular Dystrophy in Italy in the last decade: Critical issues and areas for improvements.
Despite all the advances in diagnosis and management of Duchenne muscular dystrophy over the past 50 years, the average age at diagnosis in most countries in the world around is still around 4-5 years. This retrospective study investigates the age at diagnosis in Italy in the past 10 years. We report findings from 384 boys who were diagnosed with DMD from 2005 to 2014. The mean age at first medical contact, which raised the suspicion of DMD, was 31 months. The mean age at diagnosis was 41 months. The finding that more frequently brought to suspect a DMD was the incidental finding of consistent elevated creatine kinase serum level detected during routine assessments in children undergoing general anesthesia or with intercurrent illness. This was followed by motor delay and signs of muscle weakness. Initial concerns were raised by general pediatricians (29%), specialists at tertiary centers (35%) or first level hospitals (23%). In children presenting incidental elevated creatine kinase values the diagnosis was achieved earlier than in children presenting a developmental delay. The mean age at diagnosis in our cohort was about 10-12 months lower than that reported in other countries.


Investigation of the Influence of PLA Molecular and Supramolecular Structure on the Kinetics of Thermal-Supported Hydrolytic Degradation of Wet Spinning Fibres.
In this study, differences in the kinetics of the thermal-supported hydrolytic degradation of polylactide (PLA) wet spinning fibres due to material variance in the initial molecular and supramolecular structure were analysed. The investigation was carried out at the microstructural and molecular levels by using readily available methods such as scanning electron microscopy, mass erosion measurement and estimation of intrinsic viscosity. The results show a varying degree of influence of the initial structure on the degradation rate of the studied PLA fibres. The experiment shows that hydrolytic degradation at a temperature close to the cold crystallization temperature is, on a macroscopic level, definitely more rapid for the amorphous material, while on a molecular scale it is similar to a semi-crystalline material. Furthermore, for the adopted degradation temperature of 90 °C, a marginal influence of the pH of the degradation medium on the degradation kinetics was also demonstrated.


Structure and antimicrobial activity of diterpenes from the roots of Plectranthus hereroensis.
Two abietane-type diterpenoids have been isolated from the roots of Plectranthus hereroensis (Labiatae), one being the already known horminone [1] and the other a new substance, 7 alpha,12-dihydroxy-17(15-->16)-abeo-abieta-8,12,16-triene-11 ,14-dione [2], whose structure was established by spectroscopic means. Compounds 1 and 2 showed antimicrobial activity against Staphylococcus aureus, Vibrio cholerae, Candida albicans, and Pseudomonas aeruginosa.


High-level resistance to oxidative stress in Lactococcus lactis conferred by Bacillus subtilis catalase KatE.
Lactococcus lactis, a lactic acid bacterium widely used for food fermentations, is often exposed to damaging stress conditions. In particular, oxidative stress leads to DNA, protein and membrane damages that can be lethal. As L. lactis has no catalase, the impact of production of the Bacillus subtilis haem catalase KatE on its oxidative stress resistance was tested. This cytoplasmic catalase was engineered for extracellular expression in L. lactis with an optimization strategy based on fusion to the nisin-inducible promoter and a lactococcal signal peptide (SP(Usp45)). The production of KatE by L. lactis conferred an 800-fold increase in survival after 1 h exposure to 4 mM hydrogen peroxide, and a 160-fold greater survival in long-term (3 days) survival of aerated cultures in a cydA mutant, which is unable to respire. The presence of KatE protected DNA from oxidative damage and limited its degradation after long-term aeration in a cydA/recA mutant, defective in DNA repair. L. lactis is thus able to produce active catalase that can provide efficient antioxidant activity.


[Reexamination of the communicating branch between the sural and tibial nerves].
Reexamination of communicating branches between the sural and tibial nerves ventral to the calcanean tendon was carried out on 52 legs of 26 Japanese cadavers which were used for ordinary dissection practices at the Niigata University School of Medicine. Communicating branches were found in 7 out of 52 dissections (13.5% of cases). In three of the 7 specimens, the communicating branch, the sural nerve and the tibial nerve with the deep crural fascia were removed from the legs and demonstrated by a modified Sihler's staining technique. Three types of communicating branches, Y, U and N, were distinguished on the basis of their shapes. In type Y, a medial branch from the sural nerve and a branch from the tibial nerve joined in Y-shape and become one terminal branch. In type U, the both branches formed a loop between the sural and tibial nerves. The type N communicating branch ran obliquely and medially to reach the tibial nerve distally. Only the Y type appeared in 5 specimens. Both the Y and U type and the Y and N types occurred in one specimen each. We assume that the communicating branch of the N type contains motor fibers which are derived from the sural nerve and innervate some plantar muscles, because this type is correspond to the communication type of some animals in which motor fibers have been demonstrated. Therefore, if the sural nerve biopsy is performed to examine a pure sensory nerve, removal of the more distal part of the sural nerve than a diverging point of a communicating branch is recommended. This study also indicated that the modified Sihler's staining technique is useful to examine distributions of cadaveric peripheral nerves after medical students' dissection course.


The influence of breastfeeding in breast-fed infants with atopic dermatitis.
The aim of this study was to evaluate whether breastfeeding should be discontinued for exclusively breast-fed infants with atopic dermatitis (AD). Eighty-seven exclusively breast-fed infants with AD were enrolled in a prospective observational study. The infants were divided into 3 groups: breastfeeding only (BM group), partial breastfeeding and partial partially hydrolyzed whey formula (pHF-W) (Partial group) and pHF-W only (DC group). The extent and severity of AD were evaluated with the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index at enrollment and 3 and 6 months later. There were no significant differences in parental atopy history, PO-SCORAD scores, and medication scores at baseline. At month 3 and 6, the PO-SCORAD scores were significantly decreased in all groups. PO-SCORAD scores at month 3 and 6 and at the last time point when topical corticosteroids were given were significantly different among the groups. Stepwise multiple linear regression analysis showed that baseline PO-SCORAD scores and stopping breastfeeding were significantly associated with month 3 PO-SCORAD scores (p < 0.001), after adjusting for sex, age, baseline medication scores, partial breastfeeding and parental atopy history. In addition to baseline PO-SCORAD scores and stopping breastfeeding, partial breastfeeding was significantly associated with month 6 PO-SCORAD scores. Long-term follow-up showed that only stopping breastfeeding was significantly associated with the last time point when topical corticosteroids were given (p = 0.014). For exclusively breast-fed infants with AD, discontinuing breastfeeding and shifting to pHF-W might help to improve symptoms and shorten the duration of AD regardless of sex, age and parental atopy history.


Stability of Magnesium Binary and Ternary Compounds for Batteries Determined from First Principles.
Electrochemical stability is a critical performance parameter for the materials used as electrolytes and electrodes in batteries. Using first-principles electronic structure calculations, we have determined the electrochemical stability windows of magnesium binary and ternary spinel compounds. These materials are candidates for protective coatings, solid electrolytes, and cathodes in Mg batteries, which represent a promising sustainable alternative to Li-ion batteries that still dominate the battery market. Furthermore, we have applied and assessed two different criteria for the chemical stability of the compounds. For the spinel materials, we identify the critical role of the ionic radii of the transition metal for the stability of the compounds. In addition, we determine the ion mobility in these materials using a recently developed descriptor. We thus provide guidelines for the choice of promising solid materials for Mg batteries with improved properties.


Association between coronary artery calcification and cognitive function in a Chinese community-based population.
Coronary atherosclerosis and cognitive impairment are both age-related diseases, with similar risk factors. Coronary artery calcium (CAC), a marker of coronary atherosclerosis, may play a role in early detection of individuals prone to cognitive decline. This study aimed to investigate the relationship between CAC and cognitive function, and the capability of CAC to identify participants with a high risk of dementia in a Chinese community-based population. A total of 1332 participants, aged 40-80 years and free of dementia from a community located in Beijing were included. All participants completed neurocognitive questionnaires and noncontrast CT examinations. Cognitive performance tests (including verbal memory, semantic fluency, executive function, and global cognitive function tests), the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CIDE) risk score, and the CAC score (CACS) were evaluated by questionnaires and CT. A CAIDE score ≥ 10 was considered to indicate a high risk of dementia in late-life. Participants were divided into three groups according to CACS (0, 1-399, ≥ 400). After adjusting for risk factors, CACS was significantly associated with verbal memory (r = -0.083, P = 0.003) and global cognitive function (r = -0.070, P = 0.012). The prevalence of a high risk of dementia in the subgroups of CACS = 0, 1-399, and ≥ 400 was 4.67%, 13.66%, and 24.79%, respectively (P < 0.001). Individuals with CACS ≥ 400 had a higher risk of CAIDE score ≥ 10 [OR = 2.30 (1.56, 4.56), P = 0.014] than those with CACS = 0. The receiver-operating characteristic curves showed that the capability of CACS to identify participants with a high risk of dementia was moderate (AUC = 0.70, 95% CI: 0.67-0.72,P < 0.001). CAC, a marker of subclinical atherosclerosis, was significantly associated with cognitive performance in verbal memory and global cognitive function. CAC had a moderate capability to identify participants with a high risk of dementia, independent of age, education, and other risk factors.


Brain single-photon emission computed tomography.
Single-photon emission computed tomography (SPECT) provides cost-effective information on regional cerebral perfusion and, indirectly, on regional cerebral metabolism. Its ease of use facilitates the application of SPECT in clinical neurology. SPECT is emerging as a useful tool for the management of patients with stroke, epilepsy, recurrent brain neoplasms, and some forms of dementia. The applications being investigated, such as in vivo receptor labeling for benzodiazepines, serotonin, dopamine, and muscarinic receptors, may expand the clinical usefulness of this technique in the future.


Association studies including genotype by environment interactions: prospects and limits.
Association mapping studies offer great promise to identify polymorphisms associated with phenotypes and for understanding the genetic basis of quantitative trait variation. To date, almost all association mapping studies based on structured plant populations examined the main effects of genetic factors on the trait but did not deal with interactions between genetic factors and environment. In this paper, we propose a methodological prospect of mixed linear models to analyze genotype by environment interaction effects using association mapping designs. First, we simulated datasets to assess the power of linear mixed models to detect interaction effects. This simulation was based on two association panels composed of 90 inbreds (pearl millet) and 277 inbreds (maize). Based on the simulation approach, we reported the impact of effect size, environmental variation, allele frequency, trait heritability, and sample size on the power to detect the main effects of genetic loci and diverse effect of interactions implying these loci. Interaction effects specified in the model included SNP by environment interaction, ancestry by environment interaction, SNP by ancestry interaction and three way interactions. The method was finally used on real datasets from field experiments conducted on the two considered panels. We showed two types of interactions effects contributing to genotype by environment interactions in maize: SNP by environment interaction and ancestry by environment interaction. This last interaction suggests differential response at the population level in function of the environment. Our results suggested the suitability of mixed models for the detection of diverse interaction effects. The need of samples larger than that commonly used in current plant association studies is strongly emphasized to ensure rigorous model selection and powerful interaction assessment. The use of ancestry interaction component brought valuable information complementary to other available approaches.


Microdynamics of the piezo-driven pipettes in ICSI.
Undesirably low success rates have been reported in the intracytoplasmic sperm injection procedure. Recently a method using piezo-driven pipettes with a very small mercury column contributed substantial improvements in this process. Despite the toxicity of mercury, this new procedure is commonly utilized in many laboratories. However, there is no study available to date on the micromechanics of this procedure. The underlying principles of piercing are not clear for both cases, with and without the mercury. Presently, the pressure burst, which is caused by the abrupt axial motion of the mercury column, is attributed to this effect. Here, we take the mercury-filled pipettes and try to understand the governing physics. The findings point out the occurrence of considerable lateral tip oscillations of the injection pipette as the piezoelectric pulse train is introduced. We claim that the lateral dynamics play an important role in the piercing and should be considered to enlighten the process and the effects of the mercury. These claims are analytically studied and experimentally verified.


From patchwork to package: implementing foundational capabilities for state and local health departments.
Daily public health responses are threatened by the inadequate capacity of public health agencies. A 2012 Institute of Medicine report defined a package of foundational capabilities that support all programs and services within a health department. Standardizing foundational capabilities may help address the increasing disparity in health department performance nationally. During the Fall of 2013, we collected information on how much state and local health departments knew about foundational capabilities. To our knowledge, this was the first study to assess current health department infrastructure as it relates to foundational capabilities.


Platelet Membrane Biomimetic Nanoparticles Combined With UTMD to Improve the Stability of Atherosclerotic Plaques.
Although research on the treatment of atherosclerosis has progressed recently, challenges remain in developing more effective, safer and transformative strategies for the treatment of atherosclerosis. Nanomaterials have recently played a unique role in many fields, including atherosclerosis treatment. Platelets are common component in the blood. Due to their inherent properties, platelets can target and adhere to atherosclerotic plaques. Ultrasound-targeted microbubble destruction (UTMD) shows great prospects in promoting the efficiency of drug delivery in treating solid tumors. In this study, we explored the possibility that UTMD assists platelet biomimetic rapamycin (RAP)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (RAP@PLT NPs) in the treatment of atherosclerosis. The biomimetic nano-formulations exhibit better targeting ability to plaques when administered in vivo. Targeted destruction of Sonovue™ in the aortic area further improved the efficiency of targeting plaques. Moreover, the progression of atherosclerotic plaques was inhibited, and the stability of plaques was improved. Together, our study established a novel strategy for targeted delivery of nanoparticles in atherosclerotic plaques, by combining the advantages of the ultrasonic cavitation effect and biomimicking nanoparticles in drug delivery.


General and facile purification of dye-labeled oligonucleotides by pH-controlled extraction.
Previously, we reported a method for facile purification of oligonucleotides labeled with hydrophobic dyes, based on the solubility difference between the hydrophilic DNA and unreacted dye. Here, we present a new purification method applicable to any dye regardless of its hydrophobicity. We exploited the population shift of a fluorescent dye in a low-pH aqueous solution from its anionic form toward its neutral form. When the pH of an aqueous solution containing dye-labeled DNA and unreacted free dye is lowered, and the solution is mixed with a hydrophobic organic solvent (butanol), the neutral free dye is preferentially dissolved in the organic phase, leaving behind the hydrophilic dye-labeled DNA in the aqueous phase. We experimentally verified that our new method results in high yields of dye-labeled oligonucleotides and the efficient removal of free dye.


Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats.
1. Perfluoroisobutene, a pyrolysis product of polyetrafluoroethene may cause pulmonary oedema and death when inhaled. Oral N-acetylcysteine has shown protection against inhalation of perfluoroisobutene and in this study we have tried to elucidate the mechanism by which protection is mediated. 2. Protection against the lethal effects of inhaled perfluoroisobutene has been shown when N-acetylcysteine has been orally administered 4, 6 or 8 h before gas exposure. 3. Plasma levels of cysteine, glutathione and N-acetylcysteine were increased for up to 7 h following oral administration of Nac. 4. N-acetylcysteine was not detected in the bronchioalveolar lavage fluid following oral administration. 5. Duration of protection in vivo has been related to the duration of increased thiol levels in the plasma.


A structural tree for proteins containing 3beta-corners.
A structural tree for beta-proteins with predominantly orthogonal beta-sheet packing has been constructed. The 3beta-corner, a structural motif that recurs in proteins of this class, is taken as a root structure of the tree. The 3beta-corner can be represented as a triple-stranded beta-sheet folded on to itself so that its two beta-beta-hairpins are packed approximately orthogonally in different layers and the central strand bends by approximately 90 degrees in a right-handed direction when passing from one layer to the other. The larger protein structures are obtained by stepwise addition of beta-strands to the root 3beta-corner taking into account a restricted set of rules inferred from known principles of protein structure. The protein structures that can be obtained in this way are grouped into one structural class and those found in branches of the structural tree into subclasses.


Protease inhibitor monotherapy.
The present review focuses on recent data about boosted protease inhibitor monotherapy for maintenance of HIV virological suppression. Until recently most of the trials of boosted protease inhibitor monotherapy have studied lopinavir/ritonavir monotherapy. These trials showed a slightly inferior efficacy of lopinavir/ritonavir monotherapy than that of lopinavir/ritonavir and two nucleosides. Two clinical trials [Monotherapy in Europe with TMC114 (MONET) and Monotherapy inhibitor protease (MONOI)] have shown that darunavir/ritonavir monotherapy has also a slightly lower efficacy for maintenance of virological suppression than darunavir/ritonavir with two nucleosides. The risk of resistance development is minimal and patients who fail this strategy can be re-suppressed again by adding nucleosides or switching to a triple therapy regimen without having lost therapeutic options. MONOI has also shown limb fat recovery in patients receiving darunavir/ritonavir monotherapy and good penetration of darunavir in the seminal fluid. There are still conflicting views about the ability of boosted protease inhibitor to protect the central nervous system from HIV replication. There are no randomized clinical trials showing a higher risk of discordant HIV replication in the cerebrospinal fluid in patients exposed to monotherapy. There are insufficient data of monotherapy with atazanavir/ritonavir. There currently is no consensus about the role of boosted protease inhibitor monotherapy for the treatment of HIV infection. It is clear that suppression can be maintained in a large proportion of patients without exposing patients to a substantial risk of resistance development, but the precise role of this strategy is still undefined.


Ineffectiveness of over-the-counter total-release foggers against the bed bug (Heteroptera: Cimicidae).
Field-collected bed bugs (Cimex lectularius L.) showed little, if any, adverse effects after 2-h direct exposure to the aerosolized pyrethroid(s) from three over-the-counter total-release foggers ('bug bombs' or 'foggers'); Hotshot Bedbug and Flea Fogger, Spectracide Bug Stop Indoor Fogger, and Eliminator Indoor Fogger. One field-collected population, EPM, was an exception in that there was significant mortality at 5-7 d when bugs out in the open had been exposed to the Spectracide Fogger; mortality was low when these bugs had access to an optional harborage, a situation observed for all field-collected populations when exposed to the three foggers. Even the Harlan strain, the long-term laboratory population that is susceptible to pyrethroids and that served as an internal control in these experiments, was unaffected if the bugs were covered by a thin cloth layer that provided harborage. In residences and other settings, the majority of bed bugs hide in protected sites where they will not be directly contracted by the insecticide mist from foggers. This study provides the first scientific data supporting the position that total-release foggers should not be recommended for control of bed bugs, because 1) many field-collected bed bugs are resistant to pyrethroids, and they are not affected by brief exposure to low concentrations of pyrethrins and/or pyrethroids provided by foggers; and 2) there is minimal, if any, insecticide penetration into typical bed bug harborage sites. This study provides strong evidence that Hotshot Bedbug and Flea Fogger, Spectracide Bug Stop Indoor Fogger, and Eliminator Indoor Fogger were ineffective as bed bug control agents.


Identifying measures with the highest potential to reduce suicides on Finnish railways.
The purpose of this study was to work systematically through all known measures for preventing railway suicides and to consider their suitability for the Finnish railway environment. The research method included a selection and grouping of measures, definition of assessment criteria, a literature review and compilation of assessment forms, and a workshop for experts in the field. We assessed 21 measures based on 12 specified criteria. Specifically, the aim of these criteria was to support the identification and structuring of the available information on each measure to be in easily exploitable format for railway stakeholders. The measures were listed in order of priority in three categories based on final assessments from the workshop. The measures categorised as top priority with the highest potential to reduce suicides on Finnish railways included training of railway personnel to identify suicidal people (also called Gatekeeper training), camera surveillance, detection systems (radar, movement sensors, etc.), collaboration between organisations, learning from international experience, cooperation between railway organisations, police and fire and rescue services, and training of mental health providers. This prioritisation, together with the information included in the assessment forms and expert's views related to each measure, support the Finnish railway stakeholders in selecting measures and defining implementation strategies to prevent railway suicides on Finnish railways. The insights of Finnish experts on the effectiveness and potential implementation of these different measures are valuable information also for railway stakeholders in other countries when selecting appropriate measures to prevent railway suicides. The results of this study support the safe and effective functioning of the railway system by adding knowledge that will help effectively prevent railway suicides and loss of life, delays to train traffic, and work-related stress and trauma to railway staff, rescue personnel and eyewitnesses.


Freestanding 1T-Mnx Mo1- x S2- y Sey and MoFe2 S4- z Sez Ultrathin Nanosheet-Structured Electrodes for Highly Efficient Flexible Solid-State Asymmetric Supercapacitors.
Fabrication of hierarchical nanosheet arrays of 1T phase of transition-metal dichalcogenides is indeed a critical task, but it holds immense potential for energy storage. A single-step strategy is employed for the fabrication of stable 1T-Mnx Mo1- x S2- y Sey and MoFe2 S4- z Sez hierarchical nanosheet arrays on carbon cloth as positive and negative electrodes, respectively. The flexible asymmetric supercapacitor constructed with these two electrodes exhibits an excellent electrochemical performance (energy density of ≈69 Wh kg-1 at a power density of 0.985 kW kg-1 ) with ultralong cyclic stability of ≈83.5% capacity retention, after 10 000 consecutive cycles. Co-doping of the metal and nonmetal boosts the charge storage ability of the transition-metal chalcogenides following enrichment in the metallic 1T phase, improvement in the surface area, and expansion in the interlayer spacing in tandem, which is the key focus of the present study. This study explicitly demonstrates the exponential enhancement of specific capacity of MoS2 following intercalation and doping of Mn and Se, and Fe2 S3 following doping of Mo and Se could be an ideal direction for the fabrication of novel energy-storage materials with high-energy storage ability.


LRP1 protects the vasculature by regulating levels of connective tissue growth factor and HtrA1.
Low-density lipoprotein receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is abundant in vascular smooth muscle cells. Mice in which the lrp1 gene is deleted in smooth muscle cells (smLRP1(-/-)) on a low-density lipoprotein receptor-deficient background display excessive platelet derived growth factor-signaling, smooth muscle cell proliferation, aneurysm formation, and increased susceptibility to atherosclerosis. The objectives of the current study were to examine the potential of LRP1 to modulate vascular physiology under nonatherogenic conditions. We found smLRP1(-/-) mice to have extensive in vivo aortic dilatation accompanied by disorganized and degraded elastic lamina along with medial thickening of the arterial vessels resulting from excess matrix deposition. Surprisingly, this was not attributable to excessive platelet derived growth factor-signaling. Rather, quantitative differential proteomic analysis revealed that smLRP1(-/-) vessels contain a 4-fold increase in protein levels of high-temperature requirement factor A1 (HtrA1), which is a secreted serine protease that is known to degrade matrix components and to impair elastogenesis, resulting in fragmentation of elastic fibers. Importantly, our study discovered that HtrA1 is a novel LRP1 ligand. Proteomics analysis also identified excessive accumulation of connective tissue growth factor, an LRP1 ligand and a key mediator of fibrosis. Our findings suggest a critical role for LRP1 in maintaining the integrity of vessels by regulating protease activity as well as matrix deposition by modulating HtrA1 and connective tissue growth factor protein levels. This study highlights 2 new molecules, connective tissue growth factor and HtrA1, which contribute to detrimental changes in the vasculature and, therefore, represent new target molecules for potential therapeutic intervention to maintain vessel wall homeostasis.


A Novel U-Flap Epicanthoplasty for Asian Patients.
The epicanthal fold is a distinct characteristic of the Asian upper eyelid, which may impair the beauty of the eyes and the outcome of double eyelid blepharoplasty. Although many surgical procedures have been reported, their main drawbacks include a conspicuous scar in the medial canthal area and an unnatural palpebral contour. We devised a novel surgical approach to correct the epicanthal fold with acceptable scarring. From June 2011 to October 2014, U-flap epicanthoplasty was performed on 118 Chinese patients in our department. The U-flap was designed on the medial canthal skin. After complete dissection of the flap from the dislocated orbicularis muscle and underlying connective tissue, the flap naturally rotated upward to a line consistent with the direction of the palpebral fold. The flap was then subcutaneously fixed to the medial part of the medial canthal ligament. Finally, the redundant skin was trimmed off and the incision was sutured without tension. Patients were evaluated before and 12 months after surgery. The average decrease in the intercanthal distance was 4.36 ± 0.32 mm. The general satisfaction rate was 97.5 %. Three patients showed bilateral hypertrophic scar formation on both bilateral medial canthal incisions and palpebral incisions; however, the scarring subsided after three triamcinolone acetonide injections. No epicanthal fold recurrence or other complications were observed during the 12-month follow-up period. U-flap epicanthoplasty is a simple and effective method for elimination of types I-III epicanthal folds. However, its long-term effects require further study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Tinnitus and Subjective Hearing Loss are More Common in Migraine: A Cross-Sectional NHANES Analysis.
To investigate whether migraine is independently associated with tinnitus and subjective hearing loss (HL) in a large national database. The de-identified 1999 to 2004 National Health and Nutrition Examination Survey database was retrospectively queried for subjects aged 18 to 65. HL and tinnitus were subjectively reported by subjects. A total of 12,962 subjects (52.9% female) with a mean age of 38.1 ± 14.6 years were included. This consisted of 2,657 (20.5%), 2,344 (18.1%), and 2,582 (19.9%) subjects who had migraine, subjective-HL, and tinnitus, respectively. In patients with tinnitus or subjective-HL, migraine was reported in 35.6% and 24.5%, respectively. Migraineurs were more likely to have subjective-HL (25.0% vs. 16.6%, p < 0.001) and tinnitus (34.6% vs. 16.9%, p < 0.001) compared to the nonmigraineurs. This corresponded to migraine having an odds ratio of 1.5 (95% confidence interval [CI] 1.3-1.7, p < 0.001) and 2.2 (95% CI 2.0-2.4, p < 0.001) for subjective-HL and tinnitus, respectively. After adjusting for confounders, subjective-HL (odds ratio [OR] = 1.2, 95% CI 1.1-1.4, p = 0.003), tinnitus (OR = 2.1, 95% CI 1.9-2.3, p < 0.001), and neck pain (OR = 4.0, 95% CI 3.6-4.5, p < 0.001) were more common in migraineurs. Among migraineurs, a higher proportion of those with tinnitus also had subjective-HL compared to those without tinnitus (40.0% vs. 15.3%, p < 0.001), and a higher proportion of those with subjective-HL also had tinnitus compared to those without HL (58.1% vs. 27.3%, p < 0.001). This study suggests an independent association between migraine with subjective-HL and tinnitus. Otologic migraine, which is the effects of migraine on the ear, may be partly responsible for the link between HL, tinnitus, neck pain, and migraine.


Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages☆.
Peroxisome proliferator-activated receptors (PPARs) are essential regulators of whole-body metabolism, but also modulate inflammation in immune cells, notably macrophages. We compared the effects of selective PPAR agonists to those of the pan-PPAR agonist lanifibranor in non-alcoholic fatty liver disease (NAFLD), and studied isoform-specific effects on hepatic macrophage biology. Lanifibranor or selective PPARα (fenofibrate), PPARγ (pioglitazone) and PPARδ (GW501516) agonists were therapeutically administered in choline-deficient, amino acid-defined high-fat diet (CDAA-HFD)- and Western diet (WD)-fed mouse models of NAFLD. Acute liver injury was induced by carbon tetrachloride (CCl4). The role of PPARs on macrophage functionality was studied in isolated hepatic macrophages, bone marrow-derived macrophages stimulated with palmitic acid, and circulating monocytes from patients with NAFLD. Lanifibranor improved all histological features of steatohepatitis in CDAA-HFD-fed mice, including liver fibrosis, thereby combining and exceeding specific effects of the single PPAR agonists. Its potent anti-steatotic efficacy was confirmed in a 3D liver biochip model with primary cells. Infiltrating hepatic monocyte-derived macrophages were reduced following PPAR agonist administration, especially with lanifibranor, even after short-term treatment, paralleling improved steatosis and hepatitis. Lanifibranor similarly decreased steatosis, liver injury and monocyte infiltration in the WD model. In the acute CCl4 model, neither single nor pan-PPAR agonists directly affected monocyte recruitment. Hepatic macrophages isolated from WD-fed mice displayed a metabolically activated phenotype. Lanifibranor attenuated the accompanying inflammatory activation in both murine palmitic acid-stimulated bone marrow-derived macrophages, as well as patient-derived circulating monocytes, in a PPARδ-dependent fashion. Pan-PPAR agonists combine the beneficial effects of selective PPAR agonists and may counteract inflammation and disease progression more potently. PPARδ agonism and lanifibranor directly modulate macrophage activation, but not infiltration, thereby synergizing with beneficial metabolic effects of PPARα/γ agonists. Peroxisome proliferated-activated receptors (PPARs) are essential regulators of metabolism and inflammation. We demonstrated that the pan-PPAR agonist lanifibranor ameliorated all aspects of non-alcoholic fatty liver disease in independent experimental mouse models. Non-alcoholic fatty liver disease and fatty acids induce a specific polarization status in macrophages, which was altered by lanifibranor to increase expression of lipid handling genes, thereby decreasing inflammation. PPAR isoforms have differential therapeutic effects on fat-laden hepatocytes, activated hepatic stellate cells and inflammatory macrophages, supporting the clinical development of pan-PPAR agonists.


The influence of German science on Cinchona and quinine research in Portugal in the second half of the 19th century.
This paper examines the contribution of three Portuguese scientists to Cinchona cultivation in the former Portuguese colonies in the second half of the 19th century, while discussing the importance of their studies in Germany to their professional lives. Portuguese pharmaceutical, medical, and botanical literature from the 19 th and 20 th century was reviewed, as well as books and articles regarding the history of pharmacy and medicine in Portugal. Cinchona bark, source of the antimalarial alkaloid quinine, is obtained from a South American plant, and was an important commodity in the 19th century. Many European nations (including Portugal) tried to acclimatize and cultivate Cinchona plants in their colonies. Pharmacist Joaquim dos Santos e Silva (1842-1906) performed chemical analysis of Cinchona bark samples from the Portuguese colonies in Africa. Forester Bernardino Barros Gomes (1839-1910) wrote a book with practical instructions for Cinchona cultivation and chronicled the history of Cinchona plantations in the British and Dutch colonies. In that work he also encouraged private planters to cultivate Cinchona. Forester Adolpho Frederico Möller (1842-1920), as inspector of the Botanical Garden of Coimbra, managed Cinchona plants' cultivation in the garden's nurseries, which were later sent to the colonies, and answered queries from Cinchona planters. Silva's chemistry studies in Germany were crucial to his career and the work of the three scientists was influenced and guided by their knowledge of German science and scientific culture.


Black affirming pedagogy: Reflections on the premises, challenges and possibilities of mainstreaming antiracist black pedagogy in Canadian sociology.
Antiblackness, anti-Black racism and other oppressions work within systems such as capitalism, white supremacy and globalization. As a system, Canadian higher education institutions are complicit with the oppression of Black, Indigenous and racialized peoples. Anti-oppressive and antiracist pedagogies attempt to challenge institutional power and oppression but face resistance within the academy and wider society. This paper articulates Black Affirming Pedagogy as an additional anticolonial, antiracist, pro-Black teaching praxis aimed at furthering educators' resiliencies and capacities for cultivating transformations and social change. Pro-Black affirmations of Blackness, allyship/solidarity, humanity, diverse knowledge, and action are discussed alongside strategies for praxis. Risks of engaging in Black Affirming Pedagogy and suggestions for overcoming them are also highlighted.


Evidence for a nodeless gap from the superfluid density of optimally doped Pr(1.855)Ce(0.145)CuO(4-y) films.
We present measurements of the ab-plane magnetic penetration depth, lambda(T), in five optimally doped Pr(1.855)Ce(0.145)CuO(4-y) films for 1.6 K< or =T < or =T(c) approximately 24 K. Low resistivities, high superfluid densities n(s)(T) proportional, variant lambda(-2)(T), high T(c)'s, and small transition widths are reproducible and indicative of excellent film quality. For all five films, lambda(-2)(T)/lambda(-2)(0) at low T is well fitted by an exponential temperature dependence with a gap, Delta(min), of 0.85k(B)T(c). This behavior is consistent with a nodeless gap and is incompatible with d-wave superconductivity.


Evaluation of four methods for the detection of streptococcal group A antigen directly from throat swabs.
We have compared the sensitivity, specificity and reproducibility of four rapid tests for the detection of group A beta-hemolytic streptococci antigen directly from a throat swab. The four methods were very specific, all of them offered reproductibility and surpassed conventional culture in speed and simplicity.


[Usefulness of the measurement of serum soluble IL-2 receptor alpha chain levels in clinical monitoring of non-Hodgkin lymphoma].
We measured the serum concentrations of the soluble form of interleukin-2 receptor alpha chain (sIL-2R alpha) in 25 patients with non-Hodgkin lymphoma (NHL) and 1 patient with virus-associated hemophagocytic syndrome (VHAS) by an enzyme-linked immunosorbent assay (ELISA) using two anti-IL-2R alpha monoclonal antibodies which recognize different epitopes. The sIL-2R alpha levels were markedly higher (n = 12, range = 469.2-11020 U/ml, mean +/- SD = 6153.0 +/- 1687.2 U/ml) in the sera of patients with NHL than in healthy individuals (n = 46, range = 290.1-849.3 U/ml, mean +/- SD = 459.8 +/- 126.9 U/ml, p < 0.01). The serum sIL-2R alpha levels in the NHL patients were closely associated with the stage of disease. The mean value of the serum sIL-2R alpha in each stage of NHL was as follows: stage I (469.2 U/ml, n = 1), stage II (4879.0 U/ml, n = 3), stage III (7364.8 U/ml, n = 8), stage IV (13796.2 U/ml, n = 10). However, there was no clear correlation between the elevation of serum sIL-2R alpha level and the pathological (LSG) classification of NHL. The serum sIL-2R alpha levels serially measured during the clinical course of 2 NHL patients were closely associated with the severity and the progression of the disease. Thus, the measurement of serum sIL-2R alpha levels is very useful not only for the diagnosis but also to monitor the clinical course of NHL.


Antenatal diagnostic aspects of placenta percreta and its influence on the perinatal outcome: a clinical case and literature review.
Placenta percreta is a very rare, but extremely life-threatening obstetrical pathology for the mother and the child, especially in the cases when it is not diagnosed before the birth and when it results in massive bleeding and a dramatic deterioration of condition. It is extremely important to diagnose this pathology as early as possible and plan further optimal care of patients in order to minimize life-threatening complications. The paper presents an illustrated clinical case of placenta percreta determined before the birth. Features of visual diagnostics are discussed. A 32-year-old pregnant woman with a history of two caesarean deliveries arrived at the tertiary level hospital at 22 weeks of gestation due to abdomen pain. Placenta previa was diagnosed and ultrasound, magnetic resonance imaging suggesting placenta percreta were seen. On the 32nd week, the planned caesarean hysterectomy was performed. The balloon catheters to occlude the internal iliac arteries and minimize bleeding during the surgery were used. Antenatal diagnosis of placenta percreta is especially important. Methods of visual diagnostics are complementary. The optimal surgical approach during caesarean hysterectomy remains controversial. In the case of the slow oozing without a clearly identified source of bleeding after hysterectomy and internal iliac arteries balloons deflation, ligation of one of the internal iliac arteriescan be reasonable to avoid residual haemorrhage and relaparotomy.


Hsp90 and the Fanconi anemia pathway: a molecular link between protein quality control and the DNA damage response.
Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an essential role in cell growth and survival. The chaperone exerts these functions by regulating key signaling proteins involved in cell growth/survival and protecting cells from proteotoxic stress. Importantly, Hsp90 inhibitors including geldanamycin analogues show anti-tumor effects. We recently found that Hsp90 promotes stabilization and nuclear localization of the Fanconi anemia (FA) protein FANCA, which is required for activation of the FA pathway. The FA pathway is a multiprotein biochemical pathway involved in genotoxic signaling, defects in which cause genomic instability, hematopoietic stem cell failure and tumor development. Inhibition of Hsp90 impairs the intracellular homeostasis of FANCA, resulting in disruption of the FA pathway. These findings have important implications for rational cancer chemotherapy using Hsp90 inhibitors. We also discuss the possible functions of Hsp90 in FA pathophysiology and stem cell/cancer biology. Based on our findings and other data, we propose that Hsp90 functions as "a guardian of the genome" through the control of DNA repair proteins.


Post-Translational Modifications of Transcription Factors Harnessing the Etiology and Pathophysiology in Colonic Diseases.
Defects in mucosal immune balance can lead to colonic diseases such as inflammatory bowel diseases and colorectal cancer. With the advancement of understanding for the immunological and molecular basis of colonic disease, therapies targeting transcription factors have become a potential approach for the treatment of colonic disease. To date, the biomedical significance of unique post-translational modifications on transcription factors has been identified, including phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, and O-GlcNAcylation. This review focuses on our current understanding and the emerging evidence of how post-translational regulations modify transcription factors involved in the etiology and pathophysiology of colonic disease as well as the implications of these findings for new therapeutic approaches in these disorders.


Inflammometry in pediatric asthma: a review of fractional exhaled nitric oxide in clinical practice.
The burden of pediatric asthma remains high with one-third of patients being under- or overtreated because of the unique challenges in the assessment and management of childhood asthma. Until recently, there has been no point of care tool for assessing the underlying airway inflammation (i.e., inflammometry) in asthma. Recently, fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker for the assessment and management of asthma. Recent evidence indicates that FeNO identifies T-helper cell type 2 (Th2)–mediated airway inflammation with a high positive and negative predictive value for identifying corticosteroid responsive airway inflammation. This article examines the evidence for FeNO as a predictor of Th2-mediated inhaled corticosteroid (ICS) responsive airway inflammation and reviews recent studies evaluating the role of FeNO, whether helpful or not, in the assessment and management of pediatric asthma. FeNO is a reliable adjunct to traditional tests in the assessment of suspected asthma. Importantly, it is useful for identifying and for excluding ICS-responsive airway inflammation. Although individual study results have varied, collectively, asthma managed using FeNO is associated with lower exacerbation rates compared with clinical algorithms alone. Finally, FeNO may be useful in identifying patients at risk for future impairment or loss of asthma control during reduction/cessation of ICS treatment. FeNO testing has an important role in the assessment of pediatric patients with suspected asthma and in the management of pediatric patients with established asthma. Additional studies will continue to define the exact role of FeNO testing in pediatric asthma.


Differentiating pheochromocytoma from lipid-poor adrenocortical adenoma by CT texture analysis: feasibility study.
To investigate the feasibility of using CT texture analysis (CTTA) to differentiate pheochromocytoma from lipid-poor adrenocortical adenoma (lp-ACA). Ninety-eight pheochromocytomas and 66 lp-ACAs were included in this retrospective study. CTTA was performed on unenhanced and enhanced images. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different for the objective. Diagnostic accuracies were evaluated using the cutoff values of texture parameters with the highest AUCs. Compared to lp-ACAs, pheochromocytomas had significantly higher mean gray-level intensity (Mean), entropy, and mean of positive pixels (MPP), but lower skewness and kurtosis on unenhanced images (P < 0.001). On enhanced images, these texture-quantifiers followed a similar trend where Mean, entropy, and MPP were higher, but skewness and kurtosis were lower in pheochromocytomas. Standard deviation (SD) was also significantly higher in pheochromocytomas on enhanced images. Mean and MPP quantified from no filtration on unenhanced CT images yielded the highest AUC of 0.86 ± 0.03 (95% CI 0.81-0.91) at a cutoff value of 34.0 for Mean and MPP, respectively (sensitivity = 79.6%, specificity = 83.3%, accuracy = 81.1%). It was feasible to use CTTA to differentiate pheochromocytoma from lp-ACA.


[Merkel cell carcinoma of the eyelid].
Merkel cell carcinoma is an infrequent but highly malignant cutaneous neoplasm. In a 73-year-old woman, a Merkel cell carcinoma of the right upper lid developed within 1 month, recurred within a month after its first removal, and metastasized to the parotid 2 months after secondary excision.


The Joint Action of Sesquiterpene Lactones from Leaves as an Explanation for the Activity of Cynara cardunculus.
The work described herein is a continuation of a previous study centered on the bioprospect of cardoon (Cynara cardunculus) leaf extracts through the isolation of secondary metabolites with phytotoxic activity. Chromatographic fractionations of the ethyl acetate extract and spectroscopic analysis showed that the majority of the components were sesquiterpene lactones. Of these compounds, aguerin B, grosheimin, and cynaropicrin were very active on etiolated wheat coleoptile, standard target species, and weed growth. The joint action of binary mixtures of these three active sesquiterpene lactones and one nonactive compound (11,13-dihydroxy-8-desoxygrosheimin) was studied. The activities of fixed-ratio mixtures were assessed on wheat coleoptile. The results can be interpreted with respect to a reference model by considering dose-response analyses and isobolograms with linear regression analyses. A total of 17 binary mixtures at different levels of inhibition (ED25, ED50, and ED75) were studied, and predominantly they responded additively (25). Deviations from additivity included seven synergistic responses and two antagonistic responses. The joint action of major sesquiterpene lactones isolated from C. cardunculus can explain the activities observed in extracts and fractions. The results reported here reiterate the utility of the wheat coleoptile bioassay as a quick tool to detect potential synergistic effects in binary mixtures.


Reproductive Interconception Care Among Women Recently Pregnant and Homeless: A Qualitative Analysis.
Reproductive interconception care provided at maternal postpartum visits may help reduce unintended pregnancies and elongate birth intervals for women experiencing homelessness. To improve interconception care uptake, this qualitative study aimed to identify barriers and facilitators to reproductive interconception care from the perspectives of women who were recently pregnant and homeless. A semi-structured interview guide and demographic survey were developed based on epidemiological findings, Information-Motivation-Behavioral Skill framework components, and a review by community health workers for content validity. After conducting 12 interviews with women recently pregnant and homeless in a local continuum of care in 2022, audio-recorded interviews were transcribed, iteratively coded using a priori and emerging codes, and thematically analyzed. Key themes were identified to determine implications and next steps to improving reproductive interconception care uptake. Interrelated themes focused on information (e.g., knowledge and misconceptions about pregnancy, birth intervals, contraception), motivation (e.g., attitudes about interconception care experiences, perinatal social influences), behavioral skills (e.g., objective ability to obtain interconception care and perceived self-efficacy related to attending maternal postpartum visits and increasing birth intervals), and macro-level factors (e.g., obtaining housing, contextualizing socioeconomic factors, navigating COVID-19). The findings suggest the need for flexible, streamlined, and personalized interconception care delivery that acknowledges pressing housing and relationship considerations and supports women's autonomy. Improvements to reproductive interconception care may reduce future unintended pregnancies, increase birth intervals, and improve birth outcomes among women experiencing homelessness.


The Little Girl Who Wouldn't Walk : Exploring the Narratives of Preschoolers Through Previewing.
In the psychotherapy of preschoolers, the children's narratives-in which fantasy, symbol, and metaphor are used to represent internal states and perceptions-warrant special evaluation to clarify diagnosis and implement treatment. Previewing, a developmental phenomenon of the caregiver-infant interaction, may be of benefit in the psychotherapy of preschoolers. Previewing promotes children's predictive abilities in fantasy play, sensory perception, and script formation, enabling the therapist to see the world from the child's developmental perspective and assess the child's emotional functioning without evoking pathological defenses. Moreover, previewing techniques aid in the process of conflict resolution.


Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy.
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite three decades of investigation, the biological roles of AMPK and its potential as a drug target remain incompletely understood, largely because of a lack of optimized pharmacological tools. We developed MK-8722, a potent, direct, allosteric activator of all 12 mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation in skeletal muscle induced robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia. These effects translated across species, including diabetic rhesus monkeys, but manifested with concomitant cardiac hypertrophy and increased cardiac glycogen without apparent functional sequelae.


Left ventricular diastolic collapse in regional left heart cardiac tamponade. An experimental echocardiographic and hemodynamic study.
This study was designed to describe the hemodynamic abnormalities associated with the appearance of left ventricular diastolic collapse in the setting of regional left heart cardiac tamponade. Cardiac tamponade after heart surgery is frequently associated with localized pericardial effusion. Although right ventricular diastolic collapse and right atrial collapse are reliable echocardiographic findings in patients with circumferential pericardial effusion and tamponade, they are often not present in postoperative patients with localized pericardial effusion and regional left heart tamponade. Left ventricular diastolic collapse has been described in such patients, but the degree of hemodynamic alteration that exists with this finding is not known. Acute regional left heart tamponade was produced 14 times in seven spontaneously breathing anesthetized dogs by infusing fluid into an isolated compartment created in the pericardial space adjacent to the left ventricular free wall. Continuous echocardiographic imaging and hemodynamic monitoring of left ventricular, systemic arterial, right atrial, pulmonary capillary wedge and pericardial pressures were performed. Measurements at baseline were compared with those made at the onset of left ventricular diastolic collapse and at decompensated tamponade. Left ventricular diastolic collapse was noted in all 14 episodes of regional tamponade. It occurred when pressure in the left pericardial compartment exceeded left ventricular diastolic pressure by 3.0 +/- 1.9 mm Hg. At the onset of left ventricular diastolic collapse, cardiac output and mean arterial pressure were significantly reduced from the control value (p < 0.05). Systolic hypotension was noted only twice at this stage, respiratory variation in systolic pressure > 10 mm Hg only once. The appearance of this sign was also associated with elevated left heart filling pressures. Left ventricular diastolic collapse is a reliable sign of regional left ventricular tamponade and is associated with a reduction in cardiac output. This echocardiographic finding usually occurs before the development of arterial hypotension and pulsus paradoxus. Thus, left ventricular diastolic collapse is potentially more reliable than hypotension or pulsus paradoxus in the diagnosis of regional left ventricular tamponade.


Two new species of the conger eel genus Bathycongrus (Anguilliformes: Congridae) from Taiwan.
Two new species of the congrid eel genus Bathycongrus are described from the deep waters of eastern Taiwan. Bathycongrus albimarginatus sp. nov., which belongs to the species group with two enlarged teeth on the vomer and more total vertebrae, is described from 16 specimens and can be distinguished by vertical fins with broad white margins, more pores on head and predorsal lateral line, total vertebrae 195-201. Bathycongrus brunneus sp. nov., which has no enlarged teeth on the vomer, is described from one specimen and can be distinguished by 12 subequal teeth on the vomer and 174+ total vertebrae.


Prime-boost immunization of rabbits with HIV-1 gp120 elicits potent neutralization activity against a primary viral isolate.
Development of a vaccine for HIV-1 requires a detailed understanding of the neutralizing antibody responses that can be experimentally elicited to difficult-to-neutralize primary isolates. Rabbits were immunized with the gp120 subunit of HIV-1 JR-CSF envelope (Env) using a DNA-prime protein-boost regimen. We analyzed five sera that showed potent autologous neutralizing activity (IC50s at ∼10(3) to 10(4) serum dilution) against pseudoviruses containing Env from the primary isolate JR-CSF but not from the related isolate JR-FL. Pseudoviruses were created by exchanging each variable and constant domain of JR-CSF gp120 with that of JR-FL or with mutations in putative N-glycosylation sites. The sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions located on the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera are generally distinct from those of several well characterized mAbs (targeting conserved sites on Env) or other type-specific responses (targeting V1, V2, or V3 variable regions). The activity of one serum requires specific glycans that are also important for 2G12 neutralization and this serum blocked the binding of 2G12 to gp120. Our findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth.


G protein-coupled receptor 40 activation ameliorates dextran sulfate sodium-induced colitis in mice via the upregulation of glucagon-likepeptide-2.
G protein-coupled receptor (GPR) 40 is a receptor for long-chain free fatty acids that enhances glucagon-like peptide (GLP)-2 production in intestinal L-cells. GLP-2 and its analogs have reported to increase remission rates in patients with Crohn's disease and improve experimental colitis in rodents. In the present study, we investigated the ameliorative effect of GPR40 activation in a dextran sulfate sodium (DSS)-induced murine colitis model using a specific GPR40 agonist, AS2034178. The daily administration of AS2034178 attenuated DSS-induced increases in the disease activity index, the shortening of the colon length, and the histological colonic injury, and increased the myeloperoxidase (MPO) activity and expression of inflammatory cytokines, in a dose-dependent manner. These effects were abolished by treatment with DC260126, a GPR40 antagonist, or GLP-2 (3-33), a GLP-2 antagonist. GPR40 was expressed in the colonic mucosa, which was colocalized with proglucagon, a precursor of GLP-2. AS2034178 significantly increased the amount of GLP-2 in the colonic tissue, which was abolished by DC260126 but not GLP-2 (3-33). Furthermore, AS2034178 significantly promoted the healing of DSS-induced colitis. These findings suggest that GPR40 activation ameliorates DSS-induced colitis in mice by enhancing GLP-2 production. Thus, GPR40 is a potential target for the treatment of IBD.


Plasma levels of prorenin and renin in blacks and whites: their relative abundance and associations with plasma aldosterone concentration.
All renin arises from prorenin. The proportion of renin relative to prorenin could influence overall renin-angiotensin-aldosterone activity. We sought to determine whether prorenin levels were related to extracellular volume, as reflected by the levels of plasma renin activity (PRA), and to aldosterone. We analyzed plasma levels of prorenin, renin, and aldosterone, as well as their interactions, in 129 young blacks and whites. Blacks had lower plasma renin concentration (PRC) and PRA, but had prorenin levels similar to whites (69 pg/ml in blacks vs. 62 pg/ml in whites, P = 0.41). As a result, the renin-to-total renin ratio was significantly lower in blacks (11.5% in blacks as compared to 19.8% in whites; P = 0.0001). Because prorenin also resides in tissues including the adrenal where it can bind to a specific receptor to generate angiotensin II, we examined the relationship of prorenin levels to plasma aldosterone concentrations (PAC). While a positive association between PRC and PAC was found in both blacks and whites, PAC was positively related to prorenin in whites (P = 0.04) but negatively in blacks, an observation that we hypothesize was due to reduced prorenin-to-renin conversion in blacks. We observed a disproportionately high level of prorenin in blacks. These high circulating prorenin levels however do not result in greater adrenal angiotensin II and aldosterone production in healthy young blacks.


A-Site Cation Disorder in SrxBa1-xNb2O6 (x = 0.25, 0.33, 0.50, 0.61) Studied by High-Resolution Resonant X-ray Powder Diffraction.
The dielectric and ferroelectric properties of SrxBa1-xNb2O6 (SBN, 0.2 < x < 0.8) are known to be affected by the Sr fraction and can be further controlled by various quenching schemes. Changes in A-site cation configuration are believed to be linked to these changes in properties. In this work, we study the A-site cation disorder in SBN by the use of high-resolution resonant X-ray powder diffraction. The experimental results show that the larger Ba2+ is found exclusively on the larger A2 site, while Sr2+ is found on both the A1 and A2 sites, with an increasing amount on A2 with an increasing Sr fraction. At elevated temperatures, a small migration of Sr2+ from A1 to A2 is observed for SBN50 and SBN61. Linking this change in occupancies to changes in the average cation size on the A1 and A2 sites allows for rationalization of the property changes observed for quenched samples. Furthermore, SBN25 is shown to deviate from the tetragonal P4bm structure and is found to be orthorhombic with a Cmm2 structure.


LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate.
We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N-dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland-aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N-dimethyltryptamine in pineal gland microdialysate obtained from the rat.


A closed curve is much more than an incomplete one: effect of closure in figure-ground segmentation.
Detection of fragmented closed contours against a cluttered background occurs much beyond the local coherence distance (maximal separation between segments) of nonclosed contours. This implies that the extent of interaction between locally connected detectors is boosted according to the global stimulus structure. We further show that detection of a target probe is facilitated when the probe is positioned inside a closed circle. To explain the striking contour segregation ability found here, and performance enhancement inside closed boundaries, we propose the existence of a synergetic process in early vision.


Post thaw quality and viability of vitrified immature sheep oocytes using different cryoprotectant concentrations.
The cryopreservation of oocytes through vitrification is quite successful but oocyte vitrification is still being standardized because of their structural and molecular sensitivity to the cooling and freezing processes. To evaluate the effect of different cryoprotectant concentrations on post-thaw morphology and viability of immature oocytes in sheep. Vitrification was achieved in three vitrification solutions comprised of different concentrations of the cryoprotectants ethylene glycol + DMSO, viz., (G1) 20%, (G2) 30%, (G3) 40% ethylene glycol + DMSO in equal ratio. Cryopreservation was in open pulled straws. Post vitrification evaluation was done after 1 week's storage in liquid nitrogen based on morphological evaluation and viability using trypan blue dye. The present study revealed non-significantly higher morphologically normal oocytes in G3 (74.7%) followed by G2 (70.3%), and the lowest in G1 (66.6%). Morphological defects were observed in 33.3 %, 29.6% and 25.2% of oocytes after cryopreservation in 20% (G1), 30% (G2) and 40% (G3) vitrification solutions, respectively. The results were non-significantly different between vitrification solution groups. However, the viability of post thaw immature oocytes was 95.6%%, 84.4% and 81.1% after vitrification in G1 (20%), G2 (30%) and G3 (40%), with viability being significantly highest (P<0.05) in G1 (20%) and lowest in G3 (40%). Cryoprotectant concentrations enable the maintenance of normal morphology and minimize cryoinjury during vitrification of immature oocytes.


Benzoic Acid Catalyzed Annulations of α-Amino Acids and Aromatic Aldehydes Containing an ortho-Michael Acceptor: Access to 2,5-Dihydro-1H-benzo[c]azepines and 10,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a]azepines.
A novel one-pot efficient synthesis of 2,5-dihydro-1H-benzo[c]azepines and 10,11-dihydro-5H-benzo[e]pyrrolo[1,2-a]azepines from α-amino acids and aromatic aldehydes containing an ortho-Michael acceptor is reported via decarboxylative annulations without metal catalysts in yields of 52-91%. Under microwave irradiation, this protocol provides rapid access to polycyclic ring systems (only 5 min in most cases).


Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells.
The increasingly recognized role of inflammation in the pathogenesis and prognosis of depression has led to a renewed focus on the immunomodulatory properties of compounds with antidepressant action. Studies have, so far, explored such properties in human blood samples and in animal models. Here we used the more relevant model of human hippocampal progenitor cells exposed to an inflammatory milieu, induced by treatment with IL-1β. This increased the levels of a series of cytokines and chemokines produced by the cells, including a dose- and time-dependent increase of IL-6. We investigated the immunomodulatory properties of four monoaminergic antidepressants (venlafaxine, sertraline, moclobemide, and agomelatine) and two omega-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]). We found that venlafaxine and EPA were anti-inflammatory: venlafaxine decreased IL-6, with a trend for decreases of IL-8 and IP-10, while EPA decreased the levels of IL-6, IL-15, IL-1RA, and IP-10. These effects were associated with a corresponding decrease in NF-kB activity. Unexpectedly, sertraline and DHA had pro-inflammatory effects, with sertraline increasing IFN-α and IL-6 and DHA increasing IL-15, IL-1RA, IFN-α, and IL-6, though these changes were also associated with a decrease in NF-kB activity, suggesting distinct modes of action. Agomelatine and moclobemide had no effect on IL-6 secretion. These observations indicate that monoaminergic antidepressants and n-3 PUFAs have distinctive effects on immune processes in human neural cells. Further characterization of these actions may enable more effective personalization of treatment based on the inflammatory status of patients.


Characterization of a multi-axis ion chamber array.
The aim of this work was to characterize a multi-axis ion chamber array (IC PROFILER; Sun Nuclear Corporation, Melbourne, FL, USA) that has the potential to simplify the acquisition of LINAC beam data. The IC PROFILER (or panel) measurement response was characterized with respect to radiation beam properties, including dose, dose per pulse, pulse rate frequency (PRF), and energy. Panel properties were also studied, including detector-calibration stability, power-on time, backscatter dependence, and the panel's agreement with water tank measurements [profiles, fractional depth dose (FDD), and output factors]. The panel's relative deviation was typically within (+/-) 1% of an independent (or nominal) response for all properties that were tested. Notable results were (a) a detectable relative field shape change of approximately 1% with linear accelerator PRF changes; (b) a large range in backscatter thickness had a minimal effect on the measured dose distribution (typically less than 1%); (c) the error spread in profile comparison between the panel and scanning water tank (Blue Phantom, CC13; IBA Schwarzenbruck, DE) was approximately (+/-) 0.75%. The ability of the panel to accurately reproduce water tank profiles, FDDs, and output factors is an indication of its abilities as a dosimetry system. The benefits of using the panel versus a scanning water tank are less setup time and less error susceptibility. The same measurements (including device setup and breakdown) for both systems took 180 min with the water tank versus 30 min with the panel. The time-savings increase as the measurement load is increased.


Loss of asymmetric distribution of sarcolemmal phosphatidylethanolamine during simulated ischemia in the isolated neonatal rat cardiomyocyte.
In the present study we have investigated the reorganization of the sarcolemmal phospholipids during the first 60 minutes of simulated ischemia ("ischemia") as induced by anoxia, volume restriction, and nutrient deprivation. Experiments were carried out on [3H]acetate-labeled neonatal rat cardiomyocytes and isolated (nonradiolabeled) sarcolemmal membranes obtained from the same culture system. After 60 minutes of "ischemia," cellular high-energy phosphate (ATP) levels had decreased to approximately 40% of the control values, but no significant phospholipid hydrolysis was detected. Labeling experiments using the nonpermeant (primary amine-containing phospholipid) probe trinitrobenzenesulfonic acid and nonlytic treatment with (different) exogenous phospholipases A2 were both indicative of a shifted transbilayer distribution of the hexagonalII phase-preferring and fusion-promoting sarcolemmal phosphatidylethanolamine in favor of the outer membrane leaflet. This specific change in sarcolemmal phospholipid asymmetry preceded the loss of integrity of the sarcolemma, monitored by the release of lactate dehydrogenase as well as by scanning electron microscopy. It is proposed that, in addition to the previously reported lateral phospholipid reorganization, uncontrolled transbilayer movement of the non-bilayer-preferring phosphatidylethanolamine from the inner to the outer leaflet of the sarcolemma is an additional factor in destabilizing the lipid bilayer, eventually leading to the irreversible membrane damage seen after a prolonged period of ischemia.


Simultaneous determination of neopynamine and piperonyl butoxide by capillary column gas-liquid chromatography.
A method is developed for the simultaneous determination of neopynamine and piperonyl butoxide by chromatography on a quartz capillary column using flame ionization detection. Benzyl mandelate is used as an internal standard. Calibration graphs are linear down to at least 3.75 mg% and 3 mg% for neopynamine and piperonyl butoxide, respectively.


A prospective observational study of obesity, body composition, and insulin resistance in 18 women with bipolar disorder and 17 matched control subjects.
Patients with bipolar disorder are at increased risk for diabetes and cardiovascular diseases, possibly because of more severe insulin resistance. The primary purpose of this study was to determine whether insulin resistance is characteristic of bipolar disorder. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was performed in 18 women with DSM-IV bipolar I disorder, and results were compared to those of 17 matched controls. Other risk factors were compared, including blood pressure, blood lipids, and abdominal obesity by computed tomography (CT). Additionally, substrate utilization was measured by indirect calorimetry, and free-living energy expenditure was estimated using wearable activity monitors. All data were collected between February 2006 and December 2007. Patients with bipolar disorder were no more insulin resistant than controls after accounting for generalized obesity (mean +/- SEM HOMA-IR = 2.7 +/- 0.7 vs. 2.5 +/- 0.7, for patients and controls, respectively; p = .79). Although blood lipid profiles were generally similar in patients and controls, obese patients had higher blood pressure than controls. Obese patients had more mean +/- SEM total abdominal fat (718.1 +/- 35.1 cm² vs. 607.4 +/- 33.6 cm²; p = .04), and tended (p = .06) to have more visceral abdominal fat. Patients oxidized 13% less fat during resting conditions, although their resting metabolic rate was similar to that of controls. Women with bipolar I disorder were no more insulin resistant than matched controls after accounting for their level of obesity. However, they were more hypertensive, had higher amounts of abdominal obesity, and had reduced rates of fat oxidation. Therefore, women with bipolar I disorder may be at a heightened risk for future weight gain and concomitant risk for diabetes and cardiovascular disease.


Safety of intravitreal clindamycin in albino rabbit eyes.
To study the potential toxic effects of intravitreal clindamycin on the retina of albino rabbits, by assessing functional and morphological retinal changes. Eight albino rabbits were included in the study. In each rabbit, 1 mg/0.1 ml clindamycin was injected into the vitreous of the right (experimental) eye, and 0.1 ml saline was injected into the vitreous of the left (control) eye. The electroretinogram (ERG) was recorded before injection, 3 days, 1, 2, and 4 weeks post-injection. The visual evoked potential (VEP) was recorded 4 weeks post-injection. Clinical examination was conducted at all time points. The eyes were enucleated at the termination of the follow-up period in order to prepare the retinas for histology in order to assess retinal structure. ERG and VEP responses that were recorded from the experimental eye at different times following intravitreal clindamycin injection were very similar to the corresponding responses that were recorded from the control eyes. Clinical examination was normal in all eyes, and no histological damage was observed. Intravitreal injection of 1 mg clindamycin does not cause functional or morphological signs of retinal toxicity in albino rabbits, during a period of 4 weeks post-injection. These findings support the clinical use of 1 mg intravitreal clindamycin.


The Association of State Rate Review Authority with Health Insurance Premiums.
Key findings. (1) Adjusted premiums in the individual market in states with prior approval authority combined with loss ratio requirements were lower in 2010-2013 than premiums in states with no rate review authority or file-and-use regulations only. (2) Adjusted premiums declined modestly in prior approval states while premiums increased in states with no rate review authority or with file-and-use regulations only. (3) The findings suggest that states with prior approval authority and loss ratio requirements constrained increases in health insurance premiums.


[Pulmonary infections following solid organ transplantation].
Solid organ transplantation is the standard of care for selected patients with severe vital organ dysfunction. The need for immunosuppression to prevent organ rejection is a common characteristic of recipients. Immunosuppression increases the risk of infections, especially with low virulence opportunistic pathogens. Infections following solid organ transplantation mainly affect the lungs and the airways. Establishing the diagnosis includes a wide spectrum of pulmonary diagnostics, high standard microbiological analysis and various imaging methods. With the improvement of treatment options, the number of kidney, liver, heart and lung transplant recipients is increasing and, therefore, more and more physicians may meet pulmonary complications in these patients.


Stance and swing phase costs in human walking.
Leg swing in human walking has historically been viewed as a passive motion with little metabolic cost. Recent estimates of leg swing costs are equivocal, covering a range from 10 to 33 per cent of the net cost of walking. There has also been a debate as to whether the periods of double-limb support during the stance phase dominate the cost of walking. Part of this uncertainty is because of our inability to measure metabolic energy consumption in individual muscles during locomotion. Therefore, the purpose of this study was to investigate the metabolic cost of walking using a modelling approach that allowed instantaneous energy consumption rates in individual muscles to be estimated over the full gait cycle. At a typical walking speed and stride rate, leg swing represented 29 per cent of the total muscular cost. During the stance phase, the double-limb and single-limb support periods accounted for 27 and 44 per cent of the total cost, respectively. Performing step-to-step transitions, which encompasses more than just the double-support periods, represented 37 per cent of the total cost of walking. Increasing stride rate at a constant speed led to greater double-limb support costs, lower swing phase costs and no change in single-limb support costs. Together, these results provide unique insight as to how metabolic energy is expended over the human gait cycle.


Low surface energy plane exposed Co3O4 nanocubes supported on nitrogen-doped graphene as an electrocatalyst for efficient water oxidation.
Herein, we report a simple and scalable synthesis of Co3O4 nanocubes possessing exposed low surface energy planes supported on nitrogen-doped graphene (Co3O4-NC/NGr) by a hydrothermal method as an efficient electrocatalyst for water oxidation. Three different types of morphologies of Co3O4 (i.e., nanocubes, blunt edge nanocubes and spherical particles) have been synthesized by systematically varying the reaction time. Subsequently, their catalytic activity toward oxygen evolution reaction (OER) has been screened in alkaline medium. Among the three different morphologies, the intermediate architecture (i.e., the blunt edged nanocubes designated as Co3O4-NC/NGr-12h) has shown the highest OER activity. The catalyst displayed an overpotential (η) of ∼280 mV at 10 mA/cm(2) in 1 M KOH solution, which is lower than that of the other prepared samples such as Co3O4-NC/NGr-3h (∼348 mV), Co3O4-NC/NGr-9h (∼356 mV), Co3O4-NC/NGr-24h (∼320 mV), Co3O4-NC/Gr-12h (∼300 mV) and Co3O4 (∼310 mV). Along with that, the electrochemical stability of the catalyst is also found to be remarkably good. The role of the low index planes of Co3O4 nanocubes (Co3O4-NC) and the importance of the doped nitrogen in the carbon framework for the uniform dispersion and direct coupling with Co3O4-NC have been examined. The controlled interplay of the exposed crystal planes of Co3O4 and its dispersion and synergistic interaction with the nitrogen-doped graphene are found to be the decisive factors in bringing in the modulated OER activity of the system.


[Discussion of Medical Protective Consumables Management to Fight against COVID-19 Pneumonia].
This article researches how to allocate medical protective consumables in hospital and ensure the safety of emergency marketing procurement under the condition that people are easily susceptible to COVID-19. To inform medical staffs about the standard instruction, we establish the corresponding hierarchical control management system and standards of medical protective consumables. To reduce the stress of clinical medical staff and prevent excessive protection, we enhance the training mechanisms and promote the superior normative guidance. The aim is to fully play the effectiveness of the key departments of medical protective consumables, reduce the risk of infection of clinical medical staff and ensure the safety of medical staffs.


Two types of virus-related particles are found during transmissible gastroenteritis virus morphogenesis.
The intracellular assembly of the transmissible gastroenteritis coronavirus (TGEV) was studied in infected swine testis (ST) cells at different postinfection times by using ultrathin sections of conventionally embedded infected cells, freeze-substitution, and methods for detecting viral proteins and RNA at the electron microscopy level. This ultrastructural analysis was focused on the identification of the different viral components that assemble in infected cells, in particular the spherical, potentially icosahedral internal core, a new structural element of the extracellular infectious coronavirus recently characterized by our group. Typical budding profiles and two types of virion-related particles were detected in TGEV-infected cells. While large virions with an electron-dense internal periphery and a clear central area are abundant at perinuclear regions, smaller viral particles, with the characteristic morphology of extracellular virions (exhibiting compact internal cores with polygonal contours) accumulate inside secretory vesicles that reach the plasma membrane. The two types of virions coexist in the Golgi complex of infected ST cells. In nocodazole-treated infected cells, the two types of virions coexist in altered Golgi stacks, while the large secretory vesicles filled with virions found in normal infections are not detected in this case. Treatment of infected cells with the Golgi complex-disrupting agent brefeldin A induced the accumulation of large virions in the cisternae that form by fusion of different membranous compartments. These data, together with the distribution of both types of virions in different cellular compartments, strongly suggest that the large virions are the precursors of the small viral particles and that their transport through a functional Golgi complex is necessary for viral maturation.


Blood alcohol levels. How accurately can they be guessed?
Volunteers were asked to guess their blood alcohol level immediately before having their venous level measured by gas chromatography. Thirty-one percent were able to guess to within 20 mg per 100ml of the measured amount. There was a tendency for people to over-estimate if the level was low and to under-estimate the higher values. Blood alcohol concentrations ranged from nil to 295mg per 100ml with both high and low being recorded throughout the evening.


Post-transcriptional regulation of O(6)-methylguanine-DNA methyltransferase MGMT in glioblastomas.
The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) confers therapeutic resistance to DNA alkylating agents, including temozolomide. It is largely believed that MGMT promoter methylation is associated with down regulation of MGMT transcription and corresponding protein expression, thereby predisposing tumor cells to the toxic effect of temozolomide. Here we rigorously examined this underlying assumption. We examined the correlation between MGMT promoter methylation, transcription, and protein expression using The Cancer Genome Atlas (TCGA) glioblastoma database as well as an independent collection of glioblastoma specimens. In both analyses, we found that MGMT promoter methylation status correlates well with low MGMT mRNA levels (p = 0.04). On the other hand, glioblastomas with unmethylated MGMT promoters exhibited a wide range of MGMT mRNA expression. Intriguingly, the MGMT mRNA levels correlated poorly with MGMT protein levels by Western blotting (R(2) = 0.04, p = 0.34) or by ImmunoHistoChemical (IHC) stain quantitation (R(2) = 0.02, p = 0.50). To exclude the possibility that the poor correlation was due to substandard specimens, we determined the mRNA and protein levels of Colony Stimulating Factor 1 (CSF1), a gene previously shown to exhibit excellent mRNA/protein correlation. In contrast to MGMT, the mRNA level of CSF1 correlated well with the protein level (R(2) = 0.47, p = 0.001). Importantly, long-term passaged glioblastoma cell lines with comparable MGMT transcript levels differed in MGMT protein levels, suggesting mechanisms of post-transcriptional regulation. Accordingly, the correlation between MGMT promoter methylation and MGMT protein expression was poor (p = 0.27). In silico analysis predicted potential binding sites for several miRNA within the 3'UTR of MGMT, suggesting a mechanism for the post-transcriptional of MGMT. Our results suggest mechanisms such as miRNA mediated regulation for post-transcriptional regulation of MGMT. Identification of these mechanisms should enhance the value of MGMT based prognostic or predictive biomarker strategies.


Laparoscopic liver resections - state of art.
Progress had been made in the miniinvasive surgery in the past 30 years. Laparoscopic liver procedures were expanded from limited resections to major resection and complicated procedures. Miniinvasive approach offered better short-time results and similar oncological outcomes compared with open liver surgery. However, it is still challenging to perform some difficult procedures laparoscopically which requires a learning curve and accumulation of experiences in specialized centers.