A Japanese herbal medicine attenuates anxiety-like behavior through GABAA receptor and brain-derived neurotrophic factor expression in a rat model of premenstrual syndrome.
Inochinohaha White (IHW) is a Japanese herbal medicine for treating women with anxiety associated with premenstrual syndrome (PMS). In this study, we examined the effects of IHW on anxiety-like behavior in rats undergoing progesterone withdrawal (PWD), a model for PMS. Female rats were injected daily with progesterone for 21 days. Water and ethanol extracts of IHW (WE-IHW and EE-IHW, respectively) were administered orally 15 days after the initiation of progesterone injections. Anxiety-like behavior in an elevated plus maze was evaluated 48 h after the final injection of progesterone. PWD induced anxiety-like behavior, and EE-IHW (300 mg/kg), but not WE-IHW, significantly attenuated this behavior. Administration of the GABA agonists, diazepam or muscimol, significantly attenuated PWD-induced anxiety-like behavior. To investigate the underlying mechanisms of IHW action, we analyzed GABAA receptor expression in the amygdala of these rats. EE-IHW ameliorated the PWD-induced decrease in GABAA receptor β2-subunit mRNA, although β2-subunit protein was unchanged. Brain-derived neurotrophic factor (BDNF) has been reported to have anxiolytic effects and enhance GABAergic synaptic transmission. We found that EE-IHW increased BDNF levels in a dose-dependent manner. Our results suggest that EE-IHW attenuates PWD-induced anxiety-like behavior by increasing GABAA receptor-mediated signaling via increases in β2-subunit and BDNF in the amygdala.


Complement gene expression in human brain: comparison between normal and Alzheimer disease cases.
Many investigators have reported the presence of complement proteins in Alzheimer disease (AD) brains, but their origin is uncertain. We report the expression of complement genes C1q, C3 and C4 in RNA extracted from temporal cortex samples of post-mortem human brain. The transcripts for C3 and C4 were detected by Northern hybridization analysis, and the mRNAs for C1q, C3 and C4 were detected by polymerase chain reaction (PCR) amplification of brain derived complementary DNA (cDNA). The relative abundances of mRNAs for C3 and C4 were compared between samples of temporal cortex from neurologically normal and Alzheimer disease (AD) cases, using a semiquantitative PCR assay. There was a 3.01 fold mean increase in expression of C3 and a 3.27-fold mean increase in expression of C4 in AD samples compared to control cases. These results indicate that localized synthesis of some of the major complement components can occur in human brain. The factors causing activation of complement in AD still remain undetermined.


[Abdominal obesity associated to medical-related absenteeism at a company of metal-mechanical industry in Cali, Colombia].
The aim of this study was examined the abdominal obesity prevalence and association with medical-related absenteeism. A cross-sectional study in 185 men from the metal-mechanical industry was conducted. Sociodemografic and antropometrics data of was gathered, waist circumference was measured as an indicator of abdominal obesity. The prevalence of central obesity was 28.7 %. Subjects with higher values of central obesity showed higher frequency, higher duration and higher costs of medical-related absenteeism, however, this relationship was not significant. We conclude that abdominal obesity is highly frequent in this sample; however, since it's a reversible risk, enterprises could get benefits from preventive and promotional programs destiny to control this problem.


Early postoperative epidermal growth factor receptor inhibition: safety and effectiveness in inhibiting microscopic residual of oral squamous cell carcinoma in vivo.
The local-regional failure of advanced oral squamous cell carcinoma (OSCC) after surgery results from the regrowth of residual tumor cells that may be stimulated by epidermal growth factor receptor (EGFR) ligands during the wound healing process. The level of EGFR ligands in human drain fluids (DFs) from OSCC resection and remote flap donor site were determined. A mouse model of microscopic residual OSCC was established and treated with cetuximab to measure tumor growth, survival, and cervical lymph node metastases. A mouse model of wound healing was also established to assess the effect of an EGFR antibody on the wound healing process. EGFR ligands are found in sites from OSCC resection. EGFR targeted therapy can delay tumor regrowth in a microscopic residual disease model of OSCC without significant effects on local wound healing. These results provide a strong rationale for clinical evaluation of this approach to treat patients with local-regionally advanced OSCC.


Impaction of a Percutaneous Heart Pump in Iliac Artery and Its Removal Using Snare.
In the process of forceful pulling out of an entangled placement guidewire, the percutaneous heart pump catheter folded in on itself and, on withdrawal farther down in the aorta, became impacted in the right common iliac artery. We describe the removal of this impacted catheter with the help of snare. (Level of Difficulty: Advanced.).


A retrospective descriptive study of medical record documentation of how treatment limitations are communicated with family members of patients from culturally diverse backgrounds.
Communication between clinicians and family members of patients about treatment limitation practices is essential to care-planning and decision-making. For patients and family members from culturally diverse backgrounds, there are additional considerations when communicating about treatment limitations. The objective of this study was to explore how treatment limitations are communicated with family members of patients from culturally diverse backgrounds in intensive care. A descriptive study using a retrospective medical record audit was undertaken. Medical record data were collected from patients who died in 2018 in four intensive care units in Melbourne, Australia. Data are presented using descriptive and inferential statistics and progress note entries. From 430 adult deceased patients, 49.3% (n = 212) of patients were born overseas, 56.9% (n = 245) identified with a religion, and 14.9% (n = 64) spoke a language other than English as their preferred language. Professional interpreters were used in 4.9% (n = 21) of family meetings. Documentation about the level of treatment limitation decisions were present in 82.1% (n = 353) of patient records. Nurses were documented as present for treatment limitation discussions for 49.3% (n = 174) of patients. Where nurses were present, nurses supported family members, including reassurance that end-of-life wishes would be respected. There was evidence of nurses coordinating healthcare activities and attempting to address and resolve difficulties experienced by family members. This is the first known Australian study to explore documented evidence of how treatment limitations are communicated with family members of patients from culturally diverse backgrounds. Many patients have documented treatment limitations, yet there are a proportion of patients who die before treatment limitations can be discussed with family, which may influence the timing and quality of end-of-life care. Where language barriers exist, interpreters should be used to better ensure effective communication between clinicians and family. Greater provision for nurses to engage in treatment limitation discussions is required.


Postmarketing all-case surveillance trends and contribution to safety measures of drugs approved in Japan: a cross-sectional survey in 1999-2019.
Postmarketing all-case surveillance (PACS) is a safety monitoring activity predominantly conducted for drugs with few domestic clinical trials, orphan drugs, or anticancer drugs that potentially cause serious adverse events. This study comprehensively analyzed drugs in Japan requiring PACS as an approval condition and those implementing PACS-results-based safety measures. We included drugs approved in Japan between 1999 and 2019. During the 20-year survey, 1871 drugs were approved in Japan, including 277 (14.8%) requiring PACS as an approval prerequisite. The drug number requiring PACS for approval and its ratio to the total approved-drug number is increasing annually. In 2018, the number and percentage of PACS-requiring drugs reached a 37-drug maximum (32.5%). Additionally, among the 277 PACS-requiring drugs, upon examining the results of 87 drugs for which reexamination results had already been obtained, all 87 drugs (31.4%) were found to be in Category 1 which means there is no need to revise drug-approval conditions, indicating that their usefulness is consistent with approval. Furthermore, measures such as revising the package insert and providing information to medical institutions were adopted for 53 drugs, 14 of which had PACS-results-based safety measures. PACS implementation for drug approval will potentially continue increasing. Normally, PACS is not conducted overseas, as it is a safety-monitoring activity exclusive to Japan, and the burden on institutions, such as medical sites and pharmaceutical companies, is heavy. Thus, ensuring a balance between the obtained effect and this burden is imperative.


Spatial bias induced by a non-conflictual task reveals the nature of space perception.
The aim of the present study was to show that space perception depends on sensori-motor experience. We induced spatial biases by a non-conflictual lateralized sensori-motor task on twenty seven right-handed healthy volunteers (left-to-right readers). After a pre-test and before a post-test, which assessed visuo-motor and perceptual subjective midpoint in line bisection, participants performed a short lateralized pointing task (towards the left or right hemispace). Results indicated that this lateralized pointing task induced deviations towards the stimulated hemispace in both the visuo-motor and the perceptual estimations of the subjective line centre. These spatial biases varied as a function of pointing direction (left or right pointing), spatial location and line lengths. These findings suggest that a preceding non-conflictual lateralized sensori-motor experience influences subsequent space perception. Accordingly, ecological sensori-motor experience could be involved in asymmetric perception exhibited by normal individuals and neglect patients.


Towards comparability of data: using the ICF to map the contrasting definitions of disability in Irish surveys and census, 2000-2006.
To examine how disability was measured and understood within Irish data sources 2000-2006, using the International Classification of Functioning, Disability and Health (ICF) as a guiding framework for a more comprehensive and transformative definition of disability. During the EU-funded Measuring Health and Disability in Europe (MHADIE) project (2003-2006), an audit of data sources which included a disability identifier question was conducted. Thirty Irish data sources were examined in total. An overview of these data sources was provided in 'Disability Data Sources in Ireland' (National Disability Authority, unpublished, 2007). Using guidelines developed by Cieza et al. (J Rehabil Med 2002;34:205-210, J Rehabil Med 2002;27:212-218) five data sources were selected for detailed examination and were mapped to the ICF. These were the census (2006), National Disability Survey (2006), National Physical and Sensory Disability Database (2006), Survey of Lifestyles, Attitudes and Nutrition (2002), Euro Student Survey (2003). Subsequent work conducted after the completion of the MHADIE project added to the findings. The environmental dimension of disability dominated the data collection exercises which used the ICF as their framework-for the National Disability Survey (NDS) and the National Physical and Sensory Disability Database (NPSDD). Both also had strong focus on activity and participation. When mapped on to the ICF, the data sources which preceded the ICF or did not use it, are shown to focus more on activity and participation data than any other ICF component. Across the five selected data sources, limited information was collected on body function and body structure.


Electrophoretic characterization of purified bovine, porcine, murine, rat, and human uterine estrogen receptors.
The calf uterine estrogen receptor (E2R) in the presence of sodium molybdate has been purified, 7,000-fold by a single passage over an estradiol affinity column. A dominant 70,000-dalton band and two minor bands at 50,000 and 30,000 daltons were observed by electrophoretic analysis. These bands had been eluted using estradiol, sodium sulfocyanate, CHAPS, and HEPES (pH 7.4) with insulin as a carrier protein. The identities of the protein bands were initially confirmed by their failure to bind the affinity column when saturated with estradiol. This single step purification procedure was reproducible and rapid, with yields of 10-20%, providing 25% purity. Diffusion blot analysis, with specific 35S- and 125I-labeled monoclonal antibodies to E2R, confirmed that the 70,000-dalton band represented the estrogen receptor. Specificity was demonstrated by inhibition of binding of purified E2R by both estradiol and diethylstilbestrol but not testosterone, progesterone, corticosterone, aldosterone, or hydrocortisone. The relative binding affinity of the purified receptor was: ethynyl estradiol greater than 17 beta estradiol greater than estriol greater than or equal to estrone greater than or equal to 17 alpha-estradiol greater than mestranol. Pig, human, mouse, and rat uterine estrogen receptors were similarly purified with the affinity column. As with the calf uterine preparations, a dominant 70,000-dalton band with minor bands at 50,000 and 30,000 daltons was identified by diffusion blot analysis in all the species examined.


Non-adjustable surgery for acute acquired comitant esotropia under general anesthesia.
To investigate the surgical results of the non-adjustable suture technique under general anesthesia for the correction of acute acquired comitant esotropia. Retrospective case study. Patients with acute acquired comitant esotropia who underwent corrective surgery from September 2008 to June 2018 were included. Surgical treatment was conducted based on the measured maximum angle after occlusion for at least 1 h; all surgeries were performed using the non-adjustable suture technique under general anesthesia. Motor success was categorized into three groups: good, ortho; fair, 2 to 8 prism diopters (PD); and poor, over 8 PD. Sensory success was divided into two groups: good (no diplopia with binocular vision) and poor (no stereopsis with diplopia). 40 patients (21 male and 19 female, 28.78 ± 15.32 years old) were included. Preoperative esodeviation was 28.0 ± 12.8 PD. Mean refractive error was - 2.5 ± 2.5 D (spherical equivalent). After the occlusion of one eye, 14 patients (35%) showed an esodeviation increase of more than 5 PD. There were 70% good, 25% fair, and 5% poor outcomes regarding motor success. 96% of the patients demonstrated good sensory success. The non-adjustable correction based on the maximum angle after 1 h had a relatively excellent motor and sensory success rate.


Small bowel obstruction due to Richter's hernia after laparoscopic procedures.
Two cases of a Richter's hernia through the trocar site after laparoscopic procedures are presented. A discussion of the etiology and prevention of this complication are also presented.


Automatic SCOring of Atopic Dermatitis Using Deep Learning: A Pilot Study.
Atopic dermatitis (AD) is a chronic, itchy skin condition that affects 15-20% of children but may occur at any age. It is estimated that 16.5 million US adults (7.3%) have AD that initially began at age >2 years, with nearly 40% affected by moderate or severe disease. Therefore, a quantitative measurement that tracks the evolution of AD severity could be extremely useful in assessing patient evolution and therapeutic efficacy. Currently, SCOring Atopic Dermatitis (SCORAD) is the most frequently used measurement tool in clinical practice. However, SCORAD has the following disadvantages: (i) time consuming-calculating SCORAD usually takes about 7-10 minutes per patient, which poses a heavy burden on dermatologists and (ii) inconsistency-owing to the complexity of SCORAD calculation, even well-trained dermatologists could give different scores for the same case. In this study, we introduce the Automatic SCORAD, an automatic version of the SCORAD that deploys state-of-the-art convolutional neural networks that measure AD severity by analyzing skin lesion images. Overall, we have shown that Automatic SCORAD may prove to be a rapid and objective alternative method for the automatic assessment of AD, achieving results comparable with those of human expert assessment while reducing interobserver variability.


Sustained Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Children.
Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose monovalent rotavirus vaccine (RV1) and 3-dose pentavalent rotavirus vaccine (RV5) series given in infancy against rotavirus disease resulting in hospital emergency department or inpatient care. Children were eligible for enrollment if they presented to any 1 of 3 hospitals in Atlanta, Georgia with diarrhea ≤10 days duration during January-June 2013 and were born after RV1 introduction. Stool samples were tested for rotavirus by enzyme immunoassay and immunization records were obtained from providers and the state electronic immunization information system. Case-subjects (children testing rotavirus antigen-positive) were compared with children testing rotavirus antigen-negative. Overall, 98 rotavirus-case subjects and 175 rotavirus-negative controls were enrolled. Genotype G12P[8] predominated (n = 87, 89%). The VE of 2 RV1 doses was 84% (95% CI 38, 96) among children aged 8-23 months and 82% (95% CI 41, 95) among children aged ≥24 months. For the same age groups, the VE of 3 RV5 doses was 80% (95% CI 27, 95) and 87% (95% CI 22, 98), respectively. Under routine use, the RV1 and RV5 series were both effective against moderate-to-severe rotavirus disease during a G12P[8] season, and both vaccines demonstrated sustained protection beyond the first 2 years of life.


Regulation of protein kinase C by nitroarachidonic acid: impact on human platelet activation.
Platelet activation represents a key event in normal hemostasis as well as during platelet plug formation related to thrombosis. Nitro-fatty acids are novel endogenously produced signaling mediators exerting pluripotent anti-inflammatory actions in cells and tissues. We have recently shown that nitroarachidonic acid inhibits thromboxane synthesis during platelet activation by affecting prostaglandin endoperoxide H synthase (PGHS). Herein, we investigated the regulation of human platelet activation by NO(2)AA and describe a novel mechanism involving protein kinase C (PKC) inhibition. NO(2)AA-mediated antiplatelet effects were characterized using mass spectrometry, confocal microscopy, flow cytometry, western blot and aggregometry. Incubation of NO(2)AA with human platelets caused a significant reduction in platelet sensitivity to thrombin, ADP, arachidonic acid (AA), and phorbol ester (PMA). These effects were cGMP-independent and did not involve Ca(2+) store-dependent mobilization. In contrast, signaling downstream of conventional PKC activation, such as α-granule secretion and extracellular signal regulated kinase 2 activation was strongly inhibited by NO(2)AA. Immunofluorescence confocal microscopy confirmed NO(2)AA-mediated inhibition of PKCα translocation to the membrane. In summary, we demonstrate that NO(2)AA inhibits platelet activation through modulation of PKCα activity as a potential novel mechanism for platelet regulation in vivo.


Reticular influences on lateralis posterior thalamic neurons.
(1) Spontaneous firing of lateralis intermedius-lateralis posterior (LI-LP) thalamic output cells, as well as excitatory-inhibitory sequences elicited in LI-LP neurons by anterior suprasylvian cortical and center median (CM) thalamic stimulation were studied in encéphale isolé preparations during control periods of EEG synchronization and during EEG activation induced by stimulating the mesencephalic reticular formation (RF). (2) Mean rate of spontaneous firing of identified thalamocortical neurons increased during spontaneous or RF-induced EEG activation and decreased during EEG synchronization, occuring spontaneously or elicited by hypocapnia. Compared with the sustained firing during EEG activation, discharge patterns of output cells during EEG synchronization were characterized by very short (less than 5 msec) and very long (greater than 1 sec) interspike intervals, and by a class of intervals reflecting rhythmic (2.5-4/sec) periods of neuronal silence between high-frequency spike bursts. (d) The following effects were exerted by a short conditioning mesencephalic RF stimulation on cortically evoked events in single LI or LP thalamic neurons: (a) increased probability of the early, antidromically or orthodromically elicited discharges; (b) decreased probability of late (15-25 msec) discharges; (c) shortened latency of the subsequent inhibitory period; (d) reduction in the duration of the first inhibitory phase, and blocking of subsequent, cyclic inhibitory pauses as well as disorganization of postinhibitory clustered excitation.


Longitudinal manganese and copper balances in young infants and preterm infants fed on breast-milk and adapted cow's milk formulas.
1. Mn and Cu intake and retention in twenty full-term infants and six preterm infants were studied on the basis of 72 h balances. The age of the infants was 2-16 weeks and the gestational age of the preterm infants (triplets) 34 and 36 weeks. Three nutrition schemes were pursued: breast-fed, formula-fed with unsupplemented adapted formula and formula-fed with trace element supplementation. 2. The mean Mn concentration of all breast-milk samples (n 2339) was 6.2 micrograms/l. The two formulas had similar Mn concentrations (77 and 99 micrograms/l) but had different Fe, Cu (121 and 619 micrograms/l), Zn and I contents. The mean Cu concentration in mother's milk was 833 micrograms/l. 3. The following mean daily Mn intakes and retentions (micrograms/kg) respectively were measured: breast-fed full-term 1.06 (SD 0.43) and 0.43 (SD 0.65), formula-fed full-term 14.2 (SD 3.1) and 2.8 (SD 4.8), formula-fed preterm 15.0 (SD 2.2) and 0.06 (SD 5.87). The results for Cu were 114.5 (SD 22.3) and 88.0 (SD 46.5) micrograms/kg in breast-fed, 19.8 (SD 4.2) and 4.6 (-11.5-9.6) in the unsupplemented formula-fed and 106.4 (SD 18.9) and 55.5 (SD 20.3) in the supplemented formula full-term infant group. No significant influence of the trace element contents of the formulas on the relative retention of Mn or Cu was found. 4. Young preterm infants, and to some degree young full-term infants, often had negative Mn balances caused by a high faecal excretion. The formulas with a Mn concentration below 100 micrograms/l gave a sufficient supply of Mn. Preterm infants fed on the unsupplemented formula had a marginal Cu supply and their first balances were negative (-3.8 (SD 1.8) micrograms/kg). 5. In accordance with the estimated safe and adequate daily dietary intakes (recommended dietary allowances), formula-fed infants receive much more Mn than breast-fed infants and their absolute retention is higher. 6. Cu from breast-milk had a significantly better biological availability than that from cow's milk formula. If retentions similar to those in breast-fed infants are intended, we conclude, therefore, that cow's milk formula should be fortified with Cu up to a level of at least 600 micrograms/l.


[Wall thickness of skeletal muscle microvessels and their reactivity to vasoconstrictor stimuli in normal rats and rats with spontaneous hypertension].
Wall thickness (w), wall thickness to lumen radius ratio (w/r) and vasomotor reactions produced by electrical stimulation of the sympathetic tract were studied by intravital microscopy of the skeletal muscle (extensor hallucis proprius) and compared in normal Wistar rats (NWR) and spontaneously hypertensive rats (SHR). It was established that w and w/r of arterioles with an equal lumen was greater in SHR than in NWR. Sympathetic stimulation with 6 mA, 3 imp/sec for 10 sec produced an almost 50% reduced arteriolar constriction in SHR, as compared to NWR. Linear positive correlation was shown between w/r and the degree of the lumen narrowing in both groups of animals. A bias for the increase in arteriolar response to neurogenic stimuli was manifested after a drop in blood pressure due to an acute hemorrhage in SHR. It is suggested that high blood pressure in SHR ensures the perfusion of the microcirculatory bed with a constant blood volume and prevents arteriolar constriction.


Circadian rhythm and light responsiveness of BMAL1 expression, a partner of mammalian clock gene Clock, in the suprachiasmatic nucleus of rats.
To clarify whether BMAL1 is involved in the photic signal transduction in the mammalian circadian clock, we examined the effects of a single light pulse on the level of BMAL1 mRNA in the suprachiasmatic nucleus (SCN) of rats by in situ hybridization. Rats were exposed to 30 min light of ca. 300 lux at six different phases in constant darkness and decapitated 60 min later. BMAL1 transcripts in the SCN of the control animals showed a robust circadian oscillation with the highest expression at ZT (Zeitgeber time) 18 and the lowest at ZT2. The light pulse slightly increased the level of BMAL1 transcripts in the SCN. However, the increment did not depend on the phase of light pulse. There was no significant change in the BMAL1 mRNA level up to 120 min after a light pulse at ZT14 and ZT22. These results indicate that BMAL1 transcription is not involved in the photic signal transduction responsible for non-parametric entrainment of the circadian clock in rats.


[Transient band keratopathy associated with hypercalcemia].
Band keratopathy is a corneal degenerative disease that can produce reduced visual acuity. Different ethiogical mechanisms are described, associated with ocular or systemic diseases, and treatments like EDTA, lamellar keratoplasty and excimer laser photokeratectomy. We report a male with band keratopathy and increased calcic serum that decreased after treatment. Our patient's clinical course exemplified the importance of considering systemic causes in band keratopathy, and further that the correction of calcium levels can be undertaken before other more aggressive treatments.


Reflections of an Aging Free Radical Part 2: Meeting Inspirational People.
Significance: During my long career in the field of redox biology, I met many inspiring people, especially Lester Packer. Recent Advances: This special issue of Antioxidants & Redox Signaling is dedicated to Lester Packer. Critical Issues: In this short review, I explore how Lester and other pioneers helped to develop the redox biology field and how I interacted with them. Future Directions: In our research to advance the field of redox biology, we stand on the shoulders of giants, including Lester Packer. Antioxid. Redox Signal. 38, 792-802.


Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis.
To clarify the role of interleukin-6 (IL-6) in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced by immunizing twice at a 3-week interval with bovine type II collagen (CII) emulsified with complete adjuvant. Rat anti-mouse IL-6 receptor (anti-IL-6R) monoclonal antibody MR16-1 or isotype-matched control antibody KH-5 was then injected once intraperitoneally. Symptoms of arthritis were evaluated with a visual scoring system, and serum anti-CII antibody and IL-6 levels were measured by enzyme-linked immunosorbent assay. In addition, the CII responsiveness of splenic lymphocytes from mice with CIA was examined. In mice with CIA, excess production of IL-6 in sera was observed within 24 hours after the first CII immunization, and then rapidly decreased. Serum IL-6 increased again beginning 14 days after immunization, in conjunction with the onset of arthritis. When MR16-1 was injected immediately after immunization with CII, it inhibited the development of arthritis in a dose-dependent manner. Furthermore, MR16-1-treated mice exhibited lower serum levels of IgG anti-CII antibody and reduced responsiveness of lymphocytes to CII. This suppressive effect was observed when MR16-1 was injected on day 0 or 3, but not when injected on day 7 or 14. IL-6 produced after CII immunization appears to play an essential role in the immunity to CII, and anti-IL-6R antibody reduces the development of CIA by suppressing IL-6 signal transduction.


Schnurri-2 mutant mice are hypersensitive to stress and hyperactive.
The bone morphogenetic protein (BMP)/transforming growth factor-beta (TGF-beta)/activin superfamily regulates development of the nervous system during embryogenesis and is also suggested to be involved in adult brain function. However, how BMP/TGF-beta/activin signals modulate neuronal function remains unknown. Schnurri is a transcription factor that contains two metal finger regions. Mammalian Shn-2 enters the nucleus from the cytoplasm in response to BMP-2 stimulation and plays an important role in BMP-dependent adipogenesis. To investigate whether mammalian Shn plays a role in adult brain function, we examined the behaviors of mutant mice lacking Shn-2 (Shn-2(-/-)). Shn-2(-/-) mice exhibited hypersensitivity to stress accompanied by anxiety-like behavior. Consistent with this, stress-induced corticosterone levels were significantly higher in Shn-2(-/-) mice compared to wild-type controls. Interestingly, Shn-2(-/-) mice were more active than wild-type mice in a familiar environment. The basal and stress-induced expression levels of the immediate early genes, including c-Fos, were decreased in Shn-2(-/-) mice compared to wild-type mice. Thus, Shn-2 plays a critical role in locomotion and anxiety-like behavior.


Effect of dye bath pH in dyeing of cotton knitted fabric with reactive dye (Remazol Yellow RR) in exhaust method: impact on color strength, chromatic values and fastness properties.
The significance of textile coloration is inevitable as coloration is a critical process and it can be affected by several parameters i. e. time, temperature, pH, and liquor ratio (M:L). This research reveals the behavior of different dye bath pH (2 to 12) on the basis of spectrophotometric characteristics and colorfastness using the most useable brand of reactive dye in Bangladesh i. e. Remazol Yellow RR. Earlier researches were performed on the basis of other coloration controlling factors i. e. temperature, time and liquor ratio (M:L) where pH acts as the dependent variable. However in this study, pH was taken as an independent variable where lower pH (2, 4 and 6), medium pH (8 and 10) and higher pH (12) were taken into consideration for verifying the dyeing performance. Meanwhile, the mentioned pH was achieved by adding acetic acid, soda ash and caustic soda respectively. In this study, the impact of pH is analyzed on the basis of color strength, chromaticity, hue angle, CIELAB color space, spectrophotometric image, reflectance percentage and color fastness tests i. e color fastness to rubbing, color fastness to wash, color fastness to perspiration, color fastness to light. Gradually elevated pH boosts up the color strength and chromaticity, at the same time downgrades of hue angle results orangish tone in the dyed fabric. Even more, the lightness of dyed fabric decreases and redness rises with the increment of dyebath pH which results in orangish red darker tone of dyed fabric. Consequently, fabric dyed at acidic dye bath pH exhibits higher resistance in case of color change and color staining from the dyed fabric and multifiber fabric respectively and vice versa.


Isolation of stem cells from human umbilical cord blood.
Umbilical cord blood (UCB) is gaining more prominence in recent times as a source of non-embryonic multipotent stem cells. Global annual human birth rate (100 million) presents UCB as the largest non-controversial stem cell source, with an added advantage of naive immune status. Cord blood stem cells are routinely utilized in stem cell transplantation in leukemia patients and carry huge potential to treat other human diseases with less concern of rejection. Because UCB contains low number of stem cells, their use is associated with significant delays in engraftment of neutrophils and platelets. Development of reliable methods for isolation and expansion of cord blood stem cells is critical for consequent clinical application. The focus of this chapter is to review the methods currently used by different research groups and to recommend an isolation protocol that yields optimal number of UCB stem cells.


The cochlea magnesium content is negatively correlated with hearing loss induced by impulse noise.
Magnesium is proved to attenuate acoustic trauma, and reactive oxygen species (ROS) formation is a critical role that involves hearing loss induced by impulse noise. We aimed to investigate the relationship between the cochlea magnesium content, ROS formation and hearing loss induced by impulse noise. Ninety pigmented guinea pigs were exposed to impulse noise. Auditory thresholds were assessed by sound-evoked auditory brainstem response (ABR) 24h before and 72h after exposure to impulse noise. 4-Hydroxynonenal(HNE) used as a marker of ROS was determined immunohistochemically. The cochlea magnesium content was examined with the method of energy dispersive x-ray analysis, and the cochlea was also detected with scanning electron microscope. The relationship between the cochlea magnesium content, ROS formation and hearing loss was analyzed. There was loss of outer hair cell cilia accompanying with significant auditory threshold shift after impulse noise exposure. ROS was positive in the organ of Corti of all animals. The cochlea magnesium content was negatively correlated with ROS formation and hearing loss. Inhibiting ROS formation is one of the mechanisms for magnesium to reduce acoustic trauma, and difference in cochlea magnesium contents is one of the factors that induce varying degrees of cochlear damage among each individual after acoustic trauma.


Long-term in vitro degradation of PDLLA/bioglass bone scaffolds in acellular simulated body fluid.
The long-term (600days) in vitro degradation of highly porous poly(D,L-lactide) (PDLLA)/Bioglass-filled composite foams developed for bone tissue engineering scaffolds has been investigated in simulated body fluid (SBF). Foams of ∼93% porosity were produced by thermally induced phase separation (TIPS). The degradation profile for foams of neat PDLLA and the influence of Bioglass addition were comprehensively assessed in terms of changes in dimensional stability, pore morphology, weight loss, molecular weight and mechanical properties (dry and wet states). It is shown that the degradation process proceeded in several stages: (a) a quasi-stable stage, where water absorption and plasticization occurred together with weight loss due to Bioglass particle loss and dissolution, resulting in decreased wet mechanical properties; (b) a stage showing a slight increase in the wet mechanical properties and a moderate decrease in dimensions, with the properties remaining moderately constant until the onset of significant weight loss, whilst molecular weight continued to decrease; (c) an end stage of massive weight loss, disruption of the pore structure and the formation of blisters and embrittlement of the scaffold (evident on handling). The findings from this long-term in vitro degradation investigation underpin studies that have been and continue to be performed on highly porous poly(α-hydroxyesters) scaffolds filled with bioactive glasses for bone tissue engineering applications.


A Systematic Review of Interventions to Improve Analgesic Use and Appropriateness in Long-Term Care Facilities.
To systematically review the effectiveness of interventions to improve analgesic use and appropriateness in long-term care facilities (LTCFs). Systematic review. MEDLINE, Embase, PsycINFO, and CINAHL Plus were searched from inception to June 2021. Randomized controlled trials (RCTs), controlled and uncontrolled prospective interventions that included analgesic optimization, and reported postintervention change in analgesic use or appropriateness in LTCFs were included. Screening, data extraction, and quality assessment were performed independently by 2 review authors. Eight cluster RCTs, 2 controlled, and 6 uncontrolled studies comprising 9056 residents across 9 countries were included. The 16 interventions included education (n = 13), decision support (n = 7), system modifications (n = 6), and/or medication review (n = 3). Six interventions changed analgesic use or appropriateness, all of which included prescribers, 5 involved multidisciplinary collaboration, and 5 included a component of education. Education alone changed analgesic use and appropriateness in 1 study. Decision support was effective when combined with education in 3 interventions. Overall, 13 studies reported analgesic optimization as part of pain management interventions and 3 studies focused on medication optimization. Two pain management interventions reduced the percentage of residents reporting pain not receiving analgesics by 50% to 60% (P = .03 and P < .001, respectively), and 1 improved analgesic appropriateness (P = .03). One reduced nonsteroidal anti-inflammatory drugs (NSAIDs) (P < .001) and another resulted in 3-fold higher odds of opioid prescription in advanced dementia [95% confidence interval (CI) 1.1-8.7]. One medication optimization intervention reduced NSAID prescription (P = .036), and another reduced as-needed opioid (95% CI 8.6-13.8) and NSAID prescription (95% CI 1.6-4.2). Interventions involving prescribers and enhanced roles for pharmacists and nurses, with a component of education, are most effective at changing analgesic use or appropriateness. Interventions combining education and decision support are also promising. Medication review interventions can change analgesic prescription, although there is currently minimal evidence in relation to possible corresponding improvements in resident-related outcomes.


A prospective study examining the expression of STAT 1, 3, 6 in prurigo nodularis lesions with its immunopathogenic and therapeutic implications.
Prurigo nodularis (PN) is a chronic dermatologic condition manifesting as multiple papulonodular lesions occurring on the background of intense pruritus. PN could be primary or secondary. The exact immune pathogenesis of PN is not yet clear, and multiple pathways are proposed with the JAK-STAT pathway rarely being investigated. In this study, our aim was to assess the role of Th cells in PN by comparing the expression of STAT 1, 3, and 6 in involved and normal skin of primary prurigo nodularis. A total of 49 clinico-histopathologically proven cases of primary prurigo nodularis were included. Two skin biopsies for each patient from lesional and non-lesional skin were stained with STAT 1, 3, and 6, and the nuclear staining pattern in the epidermis was graded as strong, moderate, weak, or none. Statistically significant expression of STAT 3 and STAT 6 staining was seen in the epidermis of the lesional skin as compared to non-lesional skin. Our study showed a marked dominance of STAT 3 and STAT 6 staining in the epidermis which signifies that the keratinocytes play an important role in PN and suggest that Th2, Th17, and Th22 cytokines mediate the tissue response in PN.


Ganglioside treatments reduce locomotor hyperactivity after bilateral lesions of the entorhinal cortex.
The present study evaluated the effects of exogenous gangliosides (membrane glycolipids) on open-field locomotor activity after bilateral lesions of the entorhinal cortex. Saline-treated rats showed a dramatic increase in activity followed by a time-dependent recovery (i.e. return toward control levels). Ganglioside-treated (50 mg/kg total gangliosides; i.m.) rats exhibited a similar pattern of changes in activity, except that their level of hyperactivity at 2-6 days postlesion was reduced. Thus, exogenous gangliosides lessened the severity of the lesion-induced hyperactivity, but did not enhance the total net recovery.


Influence of graft type on sagittal plane knee biomechanics during stair ambulation following anterior cruciate ligament reconstruction.
Both graft type and surgical technique for anterior cruciate ligament reconstruction can affect knee biomechanics. Several studies reported the influence of graft type, but few have controlled the surgical technique and fully investigated stair ambulation. This study aimed to compare knee biomechanics during stair ambulation between patients treated with hamstring tendon graft and those treated with patellar tendon graft when anterior medial portal technique was used to drill femoral tunnel. Two groups of patients (patellar tendon, n = 18; hamstring tendon, n = 18) at average 12 months after reconstruction surgery were recruited to ascend and descend a customized staircase in a gait lab. Joint kinematics and kinetics were calculated for both operated and contralateral intact limbs based on kinematic analysis and inverse dynamics. The influence of graft type on knee flexion angle and moment was identified using one-way mixed (graft type and limb side) analysis of variance with post-hoc paired t-test. Significant interaction between graft and limb was found for knee flexion and range of motion. Only the hamstring tendon group had significant kinematic deficits on the operated limb than the contralateral limb during stair ascent and descent. No significant interaction was found for knee flexion moment. Both graft groups had significant deficits in peak knee flexion moment on the operated side during stair ascent and descent. While the choice of graft type does not affect the restoration of knee dynamic loading, patellar tendon graft better restores knee flexion-extension kinematics during stair ambulation.


Loop-mediated isothermal amplification (LAMP) for malarial parasites of humans: would it come to clinical reality as a point-of-care test?
Loop-mediated isothermal amplification (LAMP) is a novel molecular method that accelerates and facilitates DNA amplification and detection under isothermal conditions. It represents a revolution in molecular biology by reducing the high cost, turnaround time and technicality of polymerase chain reaction and other amplification methods. It has been applied for the diagnosis of a variety of viral, bacterial, parasitic and other diseases in the biomedical field. LAMP has been involved in studies concerning the diagnosis of malaria which is still a major cause of morbidity and mortality in different parts of the world. For the success attained with this technology to diagnose human malaria, is it time to think that LAMP-based point-of-care diagnostics come to application to support the diagnosis of clinical malaria cases? The present review deals with the use of LAMP in the diagnosis of malaria and related investigations to make a view on what has been investigated and highlights the future perspectives regarding the possible applications of LAMP in diagnosis of the disease.


Amyloid beta plaque accumulation with longitudinal [18F]AZD4694 PET.
[18F]AZD4694 is an amyloid beta (Aβ) imaging agent used in several observational studies and clinical trials. However, no studies have yet published data on longitudinal Aβ accumulation measured with [18F]AZD4694. We assessed 146 individuals who were evaluated with [18F]AZD4694 at baseline and 2-year follow-up. We calculated annual rates of [18F]AZD4694 change for clinically defined and biomarker-defined groups. Cognitively unimpaired (CU) older adults displayed subtle [18F]AZD4694 standardized uptake value ratio (SUVR) accumulation over the follow-up period. In contrast, Aβ positive CU older adults displayed higher annual [18F]AZD4694 SUVR increases. [18F]AZD4694 SUVR accumulation in Aβ positive mild cognitive impairment (MCI) and dementia was modest across the neocortex. Larger increases in [18F]AZD4694 SUVR were observed in CU individuals who had abnormal amyloid positron emission tomography levels at baseline. [18F]AZD4694 can be used to monitor Aβ levels in therapeutic trials as well as clinical settings, particularly prior to initiating anti-amyloid therapies.


Antegrade Endograft Deployment with Supra-Aortic Debranching to Treat Arch and Descending Thoracic Aortic Lesions. A Single-Center Experience.
Thoracic endovascular aortic repair (TEVAR) is a widely used procedure that has drastically changed the management of thoracic aortic diseases. We assess the effectiveness of supra-aortic debranching during antegrade TEVAR procedures with a retrospective analysis of our clinical experience. Between December 2005 and April 2017, 55 patients underwent 64 TEVAR procedures. Among them, there were 8 male patients, mean age 72, who underwent hybrid antegrade stent-graft deployment. Particularly, for degenerative aneurysms of the aortic arch, 3 patients for aneurysm of descending thoracic aorta 3, for post-traumatic pseudoaneurysm 1, and for penetrating aortic ulcer 1 which had resulted in an aortoesophageal fistula. Proximal landing zones were Z0:1, Z1:3 and Z2:4. Type I hybrid aortic arch repair was performed in 1 case, carotid-carotid bypass in 2, carotid-subclavian in 5 and aorto-carotid in 1. The 30-day postoperative mortality was 12.5%. One patient suffered a temporary right hemiplegia which resolved after left aorto-carotid bypass. No endoleaks were observed postoperatively and in follow-up period. In the long term and a mean follow-up of 4.9 years, there were no deaths related to the stent-graft implantation or to revascularization procedures. Regarding the aortic arch rerouting procedure, there were no pseudoaneurysm or other anastomotic events. Antegrade delivery of the endograft, combined with hybrid and revascularization procedures of the supra-aortic vessels is a safe treatment modality, in complex hostile anatomies. However, further improvements are recommended due to the presence of neurologic complications and reinterventions.


Level 5 Lymphadenopathy Warrants Heightened Suspicion for Clinically Significant Pathology.
We conclude that patients presenting with level 5 lymphadenopathy should be investigated with heightened clinical vigilance. Our results suggest that up to 80 % will harbour clinically significant pathology requiring further medical treatment, three quarters of which will be malignancy. We report an observational study of histological outcomes of level 5 lymph node biopsies from a regional histopathology department across 5 years. 184 subjects were identified as having a biopsy of a lymph node from the level 5 region within the study period. One hundred and fifty six cases (84.8 %) had clinically significant pathology on final histology requiring further medical treatment. Lymphoma accounted for the highest number of cases (n = 72, 39.1 %), followed by metastatic carcinoma (n = 65, 35.3 %) and granulomatous change (n = 17, 9.2 %). Gender and laterality were not shown to be independent predictors of pathology significance (p > 0.05).


Trajectories of distress and recovery, secondary stressors and social cure processes in people who used the resilience hub after the Manchester Arena bombing.
Terrorist incidents lead to a range of mental health outcomes for people affected, sometimes extending years after the event. Secondary stressors can exacerbate them, and social support can provide mitigation and aid recovery. There is a need to better understand distress and mitigating factors among survivors of the Manchester Arena attack in 2017. We explored three questions. First, what experiences of distress did participants report? Second, how might secondary stressors have influenced participants' psychosocial recoveries? Third, what part has social support played in the relationships between distress and participants' recovery trajectories? We conducted a cross-sectional online survey of a convenience sample of survivors of the Manchester Arena bombing (N = 84) in January 2021 (3 years 8 months post-incident), and a longitudinal study of the same participants' scores on mental health measures over 3 years from September 2017. Survivors' mental well-being scores in early 2021 were significantly lower than general population norms. Longitudinal follow-up provided evidence of enduring distress. Secondary stressors, specifically disruptions to close relationships, were associated with greater post-event distress and slower recovery. We found an indirect relationship between identifying with, and receiving support from, others present at the event and mental well-being >3 years later. The Arena attack has had an enduring impact on mental health, even in survivors who had a mild response to the event. The quality of close relationships is pivotal to long-term outcome. Constructive support from family and friends, and people with shared experiences, are key to social cure processes that facilitate coping and recovery.


Development and characterization of an automated imaging workflow to generate clonally-derived cell lines for therapeutic proteins.
In the development of biopharmaceutical products, the expectation of regulatory agencies is that the recombinant proteins are produced from a cell line derived from a single progenitor cell. A single limiting dilution step followed by direct imaging, as supplemental information, provides direct evidence that a cell line originated from a single progenitor cell. To obtain this evidence, a high-throughput automated imaging system was developed and characterized to consistently ensure that cell lines used for therapeutic protein production are clonally-derived. Fluorescent cell mixing studies determined that the automated imaging workflow and analysis provide ∼95% confidence in accurately and precisely identifying one cell in a well. Manual inspection of the images increases the confidence that the cell line was derived from a single-cell to >99.9%. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:584-592, 2018.


Comparison of surgical and endovascular treatments for fusiform intracranial aneurysms: systematic review and individual patient data meta-analysis.
Fusiform intracranial aneurysms (FIA) are associated with significant morbidity and mortality. We carried out a systematic review and meta-analysis of individual participant data with propensity score adjustment to compare the functional and angiographic outcomes between surgical and endovascular approaches to FIA. We conducted a systematic review for articles on the treatment of FIA with individual patient-level detailing. Data from patients treated for FIA in our institution from 2010 to 2018 were also collected. The primary studied outcome was morbidity, and secondary outcomes were angiographic results and retreatment. Propensity score-adjusted mixed-effects logistic regression models evaluated treatment options, stratified by anatomical location. Compiling original and published data, there were 312 cases, of which 79 (25.3%) had open surgery, and 233 (74.5%) were treated with endovascular procedures. There were no differences between treatment groups, for neither cavernous ICA (OR 1.04, 95% CI 0.05-23.6) nor supraclinoid aneurysms (OR 7.82, 95% CI 0.65-94.4). Both size (OR 1.11, 95% CI 1.03-1.19) and initial mRS (OR 2.0, 95% CI 1.2-3.3) were risk factors for morbidity, independent of location. Neither age nor rupture status influenced the odds of posterior morbidity. Unfavorable angiographic outcomes were more common in the endovascular group for supraclinoid and vertebrobasilar aneurysms (χ2, P < 0.01). There were no differences between morbidity of surgical and endovascular treatments for FIA, regardless of aneurysm location. Size and initial mRS were correlated with functional outcomes, whereas age and rupture status were not. Microsurgery seems to yield better long-term angiographic results compared to endovascular procedures.


Comparison between anterolateral thigh free flap and jejunal flap for tissue reconstruction in patients underwent resection of pharyngoesophageal squamous cell carcinoma after radiotherapy failure: a retrospective study.
Anterolateral thigh (ALT) free flap and jejunal flap (JF) were commonly used in tissue reconstruction for pharyngoesophageal squamous cell carcinoma (PESCC) with worsening tissue adhesion and necrosis after radiotherapy failure. However, the results of tissue reconstruction and postoperative complications of these two flaps are controversial. The purpose of this study was to compare outcomes between group ALT free flap and group JF in PESCC after radiotherapy failure. Intraoperative information and postoperative outcomes of patients with PESCC after radiotherapy failure who underwent ALT and JF reconstruction from January 2005 to December 2019 were compared and analyzed. The defect size of ALT (Numbers, 34) and JF (Numbers, 31) was 36.19 ± 11.35 cm2 and 35.58 ± 14.32 cm2 (p = 0.884), respectively. ALT and JF showed no significant difference in operation time (p = 0.683) and blood loss (p = 0.198). For postoperative outcomes within 30 days both in recipient site and donor site including wound bleeding, wound dehiscence, wound infection, and pharyngocutaneous fistula, ALT free flap and JF showed similar results. Flap compromise (Numbers, 2 VS.3, p = 0.663), flap take backs (Numbers, 1 VS.1, p = 1.000), partial flap failures (Numbers, 4 VS.2, p = 0.674), and total flap failures (Numbers, 0 VS.0, p = 1.000) showed no difference between the two groups. In addition, no significance was found in hypoproteinemia between the two groups (Numbers, 4 VS.2, p = 0.674). ALT free flap was not statistically different from JF in the incidence of dysphagia at the postoperative 6 months (Numbers of liquid diet, 5VS.5; Numbers of partial tube feeding, 6VS.7; Numbers of total tube feeding, 3VS.1, p = 0.790) and 12 months (Numbers of liquid diet, 8VS.7; Numbers of partial tube feeding, 8VS.7; Numbers of total tube feeding, 5VS.5, p = 0.998). The cause of dysphagia not found to differ between the two groups both in postoperative 6 months (p = 0.814) and 12 months (p = 0.845). Compared with JF, ALT free flap for PESCC patients after radiotherapy failure showed similar results in postoperative outcomes. ALT free flap may serve as a safe and feasible alternative for PESCC patients after radiotherapy failure.


Fructose bisphosphate aldolase from rabbit muscle. A jump in the van't Hoff plot accompanies the onset of half of the sites' reactivity.
In 40% ethylene glycol, gamma/2 = 0.11 and pH* 8.2, fructose 1,6-bisphosphate aldolase from rabbit muscle undergoes a transition: above 3 degrees C it displays 4 equivalent dihydroxyacetone phosphate binding sites, below -1 degree C the sites decrease to 2. The dissociation constant of the aldolase-dihydroxyacetone phosphate complex decreases from 10 microM at 3 degrees C to 2.65 microM at -1 degree C, its van't Hoff plot being linear between -1 degree C and -13 degrees C. The rate of the detritiation of the aldolase-(3S)-[3-3H]dihydroxyacetone phosphate complex is strongly influenced by temperature. In 40% ethylene glycol, gamma/2 = 0.01 and pH* 8.2, the apparent rate constant is 7.6 sec-1 at -5 degrees C and 0.012 sec-1 at -24 degrees C. The Arrhenius plot is linear between -5 degrees C and -24 degrees C.


Occurrence of ochratoxin A in herbal drugs of Indian origin - a report.
This paper contains a report of occurrence of ochratoxin A in some common herbal medicines collected from different store-houses and shop-keepers of Bihar, India. Of 129 samples of 9 plants, 55 were found to be contaminated with various levels of ochratoxin A. The level of ochratoxin A was found maximal in barks ofHolarrhena antidysenterica (1.14 - 2.34 μg/g) whereas it was minimal in rhizomes ofTacca aspera (0.3 - 0.74 μg/g).Aspergillus ochraceus, A sulphureus and Penicillium viridicatum isolates obtained from drug samples were also examined for their toxigenic potentials. 19 isolates ofA ochraceus, 13 ofA sulphureus and 37 isolates ofP viridicatum were found to be toxigenic out of 67, 33, and 107 isolates, respectively. The ochratoxin A produced by Aochraceus was in the range of 0.09 to 2.44 μg/mL, byA sulphureus 0.1 to 1.76 μg/mL, and byP viridicatum 0.14 to 2.78 μg/mL of the culture filtrate.


Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: The available clinical data.
Cardiovascular diseases are the primary cause of death and the leading cause of disability in industrialized countries. Dyslipidemia is a major independent and reversible risk factor for these diseases: it is estimated that a reduction of 1 mmol/l (38 mg/dl) of LDL cholesterol is associated with a risk of developing a cardiovascular complication reduced by 25%, a reduction potentially achieved by life-style improvement associated to adequate dietary supplementation with bioactive substances. The aim of this review is to focus on the major phytochemical nutraceuticals combinations supported by clinical trials that have demonstrated positive effects in the treatment of dyslipidemia. There are many nutraceuticals with significant lipid-lowering properties: most of them are used in association with a low dosage, because that permits to reduce the risk of side effects and theoretically to improve efficacy. In fact, natural products with different synergetic lipid-lowering could be combined: they can reduce the absorption of lipids from the bowel and/or increase their excretion (soluble fibers, plant sterols, probiotics), enhance the hepatic uptake of cholesterol (berberine, soybean proteins), inhibit Hydroxy-Methil-Gglutaryl Coenzyme A reductase enzyme and consequently the hepatic synthesis of cholesterol (monacolins, policosanols, allicin, soybean proteins, bergamot); furthermore some products are able to reduce the oxidation of the LDL and increase the thermogenesis and lipid metabolism (chlorogenic acid). Rational combinations of nutraceuticals with different lipid-lowering activities, whether associated with an appropriate lifestyle, should provide an alternative to drug treatment in patients in primary cardiovascular disease prevention with mildly added cardiovascular risk and in some statin-intolerant patients.


The effects of lithium isotopes on the myo-inositol 1-phosphatase reaction in rat brain, liver, and testes.
Enzyme inhibition studies were performed with several lithium isotopes in order to more precisely define how lithium inhibits the enzyme myo-inositol 1-phosphatase. This lithium-induced inhibition is thought to be central to the therapeutic effects of lithium in the treatment of manic-depressive disorder. Naturally occurring lithium (NLi) exists as a combination of isotopes: 6Li and 7Li. Lethality studies were performed comparing 6LiCl, 7LiCl, and NLiCl, did not demonstrate a differential effect as previous studies had suggested. Enzyme inhibition studies were performed with these individual lithium isotopes, and compared to the effects of the naturally occurring combination (NLi) on the inhibition of myo-inositol 1-phosphatase using a partially purified enzyme preparation from rat brain, liver and testes. Identical inhibition was observed with all lithium isotopes and their combinations. In addition, both D- and L-myo-inositol 1-phosphates were used as enzyme substrates and found to be equivalent. These experiments, along with previous work demonstrating lithium acting as an uncompetitive inhibitor in the reaction, and the lack of lithium binding sites on the enzyme, suggests the hypothesis that lithium is possibly inhibiting this reaction by interfering with the formation of a transition cyclic intermediate, myo-inositol 1,3-cyclic phosphate, which may be formed from either the D- or L-substrates. This proposal is in contrast to previous suggestions regarding the inhibitory mechanism of action of lithium on the myo-inositol 1-phosphatase reaction.


A recurring theme in protein engineering: the design, stability and folding of repeat proteins.
Repeat proteins are ubiquitous and are involved in a myriad of essential processes. They are typically non-globular structures that act as diverse scaffolds for the mediation of protein-protein interactions. These excitingly different structures, which arise from tandem arrays of a repeated structural motif, have generated significant interest with respect to protein engineering and design. Recent advances have been made in the design and characterisation of repeat proteins. The highlights include re-engineering of binding specificity, quantitative models of repeat protein stability and kinetic studies of repeat protein folding.


Cost comparison of immediate angioplasty versus thrombolysis followed by conservative therapy for acute myocardial infarction: a randomized prospective trial. Mayo Coronary Care Unit and Catheterization Laboratory Groups.
Immediate angioplasty and thrombolysis followed by conservative therapy are treatment strategies for acute myocardial infarction. The objective of this study was to compare the costs of these two strategies during a 12-month period. Of 103 patients with acute myocardial infarction who sought medical assistance within 12 hours after onset of symptoms, 4 were excluded from analysis for various reasons, 51 received tissue plasminogen activator, and 48 underwent immediate angioplasty as the initial revascularization strategy. The main outcome determinants were direct monetary costs and indirect measures of costs, including duration of hospital stay and return to work. No significant difference in monetary costs between the two initial treatment strategies could be demonstrated. A trend was noted toward a briefer hospital stay and fewer late in-hospital procedures for patients treated initially with immediate angioplasty. Other measures of indirect costs were not statistically different. The hypothesis that thrombolysis followed by conservative therapy would be more cost-effective than immediate angioplasty in the treatment of patients with acute myocardial infarction could not be substantiated. The two strategies seem to have similar cost-effectiveness.


Acute Toxicity and Sublethal Effects of Lemongrass Essential Oil and Their Components against the Granary Weevil, Sitophilus granarius.
In the present work, we evaluate the toxic and repellent properties of lemongrass (Cymbopogon citratus (DC. ex Nees) Stapf.) essential oil and its components against Sitophilus granarius Linnaeus as an alternative to insecticide use. The lethal dose (LD50 and LD90), survivorship, respiration rate, and repellency on adults of S. granarius exposed to different doses of lemongrass oil and some of its components were evaluated. The chemical composition of the essential oil was found to have the major components of neral (24.6%), citral (18.7%), geranyl acetate (12.4%), geranial (12.3%), and limonene (7.55%). Lemongrass essential oil (LD50 = 4.03 µg·insect-1), citral (LD50 = 6.92 µg·insect-1), and geranyl acetate (LD50 = 3.93 µg·insect-1) were toxic to S. granarius adults. Survivorship was 99.9% in insects not exposed to lemongrass essential oil, decreasing to 57.6%, 43.1%, and 25.9% in insects exposed to LD50 of essential oil, citral, and geranyl acetate, respectively. The insects had low respiratory rates and locomotion after exposure to the essential oil, geranyl acetate, and citral. Our data show that lemongrass essential oils and their components have insecticidal and repellent activity against S. granarius and, therefore, have the potential for application in stored grain pest management schemes.


Prognostic impact of preexisting hypertension and high systolic blood pressure at admission in patients hospitalized for systolic heart failure.
Higher systolic blood pressure (SBP) has been reported to be associated with a better prognosis in heart failure (HF) patients. This study aimed to investigate the prognostic impact of hypertension in patients hospitalized with systolic HF. Pooled analysis of data from three Korean observational studies was performed. Patients ≥18 years hospitalized with systolic HF (ejection fraction ≤45%) (n=3538) were compared for the incidence of 1-year all-cause mortality according to the presence of preexisting hypertension and SBP quartiles on admission. Patients with hypertension (prevalence, 51.6%) presented more often with diabetes (43.9% vs. 23.0%, p<0.001) and chronic kidney disease (14.1% vs. 5.7%, p<0.001). During the 1-year follow-up, patients with hypertension showed similar cumulative incidences of all-cause mortality as those without hypertension (8.3% vs. 8.4%, p=0.900). Conversely, patients with higher SBP on admission had a lower incidence of all-cause death (quartile 4 vs. 1: 6.7% vs. 11.3%, p for trend=0.004). In the multivariate analysis, an increase in SBP of 10 mmHg was associated with an 8.5% risk reduction of all-cause death (hazard ratio: 0.915, 95% confidence interval: 0.853-0.981, p=0.013). Higher SBP on admission was independently associated with a lower risk of 1-year all-cause mortality in systolic HF.


Vapour toxicity of aerosol formulation, allethrin on Culex quinquefasciatus (Diptera: Culicidae), Say & Musca domestica (Diptera: Muscidae) N.
Studies on the toxicity of aerosol vaporizer formulation, allethrin were carried out on both male and female species of C. quinquefasciatus and M. domestica at different times of exposure. ANOVA models revealed significant differences in the mean values of the percentage mortalities in relation to sex and time-of-exposure for both the species.


Combined esterified estrogens and methyltestosterone versus esterified estrogens alone in the treatment of loss of sexual interest in surgically menopausal women.
To compare the effect of esterified estrogens and methyltestosterone versus esterified estrogens alone on diminished sexual interest in surgically menopausal women. This randomized, double-blind study compared the effect of combined esterified estrogens (1.25 mg) and methyltestosterone (2.5 mg) (EE/MT) versus esterified estrogens (1.25 mg) alone (EE) for 8 weeks. Several different sexual function questionnaires were used to measure response to therapy. Changes from baseline in sexual interest/function and hormone levels were evaluated after 4 and 8 weeks of treatment. A total of 102 women were randomized into the study; 52 (age range, 32-61 years) to EE/MT and 50 (age range, 33-62 years) to EE. After 8 weeks, significant differences between treatments were not seen in the Changes in Sexual Functioning Questionnaire (CSFQ-F-C) sexual desire/interest subscale score, the primary efficacy variable. In contrast statistically significant between-treatment differences were found for several secondary efficacy variables including Menopausal Sexual Interest Questionnaire (MSIQ) sexual interest/desire score, CSFQ-F-C arousal/erection subscale score and Women's Health Questionnaire sexual functioning subscale score. The mean serum concentration of bioavailable and free testosterone significantly increased, approximately doubling between baseline and the end of the study in patients receiving EE/MT, with a significant (P < 0.001) between-treatment difference. The mean serum concentration of sex hormone-binding globulin significantly decreased to less than one third of the pretreatment levels in patients receiving EE/MT (P < 0.001). Both treatments were well tolerated. The mixed results seen with the different sexual function questionnaires may be due to the CSFQ-F-C's lack of specificity for this population. Increased levels of bioavailable and free testosterone paralleled the improved MSIQ item scores. Both the EE and EE/MT treatments were well tolerated.


Expression of a renal Na/Pi cotransporter (NaPi-1) in MDCK and LLC-PK1 cells.
We have recently isolated a corresponding DNA (cDNA) (NaPi-1) which, most likely is related to rabbit renal proximal tubular Na/Pi cotransport. In the present study we have stably transfected Madin Darby canine kidney (MDCK) and LLC-PK1 cells with a vector containing the NaPi-1 cDNA under the control of a dexamethasone-inducible promoter. In transfected MDCK and LLC-PK1 cells, NaPi-1-related mRNA could be detected by reverse transcription-polymerase chain reaction (RT-PCR) only after induction of the cells by dexamethasone. Similarly an increase in Na(+)-dependent Pi uptake was observed in NaPi-1 transfected MDCK and LLC-PK1 cells grown in Petri dishes and stimulated by dexamethasone; in cells grown on filter supports, dexamethasone-induced transport activity in NaPi-1 transfectants was only observed at the apical cell surface.


Danhe granule ameliorates nonalcoholic steatohepatitis and fibrosis in rats by inhibiting ceramide de novo synthesis related to CerS6 and CerK.
Danhe granule (DHG) is used by Chinese doctors to treat blood stasis, phlegm and dampness. Its lipid-lowering ability has been investigated in our previous research. However, the anti-liver inflammatory and fibrotic effects and mechanism of action of DHG in non-alcoholic steatohepatitis (NASH) have not been explored. To evaluate the ameliorative effects of DHG on liver inflammation and fibrosis in a methionine/choline-deficient (MCD) diet-induced NASH rat model, and its underlying mechanism. Sprague-Dawley rats were fed an MCD diet for two weeks and then treated with or without DHG by oral gavage for eight weeks. Their body weight and liver index were measured. The serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities as well as the liver triglyceride (TG) and free fatty acid (FFA) levels were tested using reagent kits. Inflammatory cytokines, including Tnf-α, Il-β and Il-6, and fibrosis genes, including Acta2, Col1a1, Col1a2 and Tgf-β were examined by real-time quantitative PCR (RT-qPCR). Hematoxylin-eosin (H&E), Oil Red O, Masson's and Sirius Red staining were used to observe liver changes. The plasma and liver ceramide levels were analyzed using HPLC-QQQ-MS/MS. The expression of serine palmitoyl-CoA transferase (Spt), ceramide synthase 6 (Cers6), dihydroceramide desaturase 1 (Des1), glucosylceramide synthase (Gcs), and ceramide kinase (Cerk) mRNA was assayed by RT-qPCR, while the protein expression of CerS6, DES1, GCS, CerK, and casein kinase 2α (CK2α) was tested by western blotting (WB). CerS6 degradation was evaluated using a cycloheximide (CHX) assay in vitro. The liver index decreased by 20% in DHG groups and the serum ALT and AST decreased by approximately 50% and 30%, respectively in the DHG-H group. The liver Oil Red O staining, TG, and FFA changes showed that DHG reduced hepatic lipid accumulation by approximately 30% in NASH rats. H&E, Masson's and Sirius Red staining and the mRNA levels of Tnf-α, Il-β, Il-6, Acta2, Col1a1, Col1a2 and Tgf-β revealed that DHG alleviated liver inflammation and fibrosis in NASH rats. The ceramide (Cer 16:0), and hexosylceramide (HexCer 16:0, HexCer 18:0, HexCer 22:0, HexCer 24:0 and HexCer 24:1) levels decreased by approximately 17-56% in the plasma of the DHG-M and H rats. The Cer 16:0 content in the liver decreased by 20%, 50%, and 70% with the DHG-L, M, and H treatments; additionally, the dhCer 16:0, Cer 18:0, HexCer 18:0, HexCer 20:0 Cer 22:0-1P, Cer 24:0-1p, Cer 24:1-1p, and Cer 26:1-1p levels decreased in the DHG groups. The mRNA and protein expression levels of DES1, GCS, Cerk, CerS6, and CHX assay indicated that DHG decreased the mRNA and protein expression levels of CerK and reduced CerS6 protein expression by promoting its degradation. Additionally, DHG attenuated the protein expression of CK2α which could increase CerS6 enzymatic activity by phosphorylating its C-terminal region. DHG ameliorated the levels of liver FFA and TG and inflammation and fibrosis in MCD-induced rats, which were associated with decreasing ceramide species in the plasma and liver by reducing the expression levels of CerS6 and CerK.


Heterozygous manifestations of Langer mesomelic dysplasia.
The mesomelic dysplasias are a heterogeneous group of genetic disorders with predominant skeletal manifestations in the forearms and shanks. We have documented, over a thirteen-year period, the clinical and radiographic course of the condition in a boy with the Langer type of mesomelic dysplasia. It has been suggested that dyschondrosteosis or the Madelung deformity are the phenotypic manifestations of the gene which causes Langer mesomelic dysplasia in the homozygote. Several relatives on both sides of the family which we studied had malformations of their forearms, in keeping with this concept. However, these anomalies differed from those of dyschondrosteosis and the classical Madelung deformity; the exact syndromic status of the heterozygous phenotype remains unsettled.


H(2)S and HS(-) donor NaHS releases nitric oxide from nitrosothiols, metal nitrosyl complex, brain homogenate and murine L1210 leukaemia cells.
Nitrosoglutathione [(GSNO), 500 nmol/l] relaxed the norepinephrine precontracted rat aortic rings. The relaxation effect was pronouncedly enhanced by H(2)S- and HS(-)-donor NaHS (30 micromol/l) at 7.5 pH but not at 6.3 pH. To study molecular mechanism of this effect, we investigated whether NaHS can release NO from NO donors. Using an electron paramagnetic resonance spectroscopy method of spin trap and by measuring the NO oxidation product, which is nitrite, by the Griess reaction, we report that NaHS released NO from nitrosothiols, namely from GSNO, S-nitroso-N-acetyl-DL: -penicillamine (SNAP), from metal nitrosyl complex nitroprusside (SNP) and from rat brain homogenate and murine L1210 leukaemia cells. From the observation that the releasing effect was more pronounced at 8.0 pH than 6.0 pH, we suppose that HS(-), rather than H(2)S, is responsible for the NO-releasing effect. Since in mammals, H(2)S and HS(-) are produced endogenously, we assume that their effect to release NO from nitrosothiols and from metal nitrosyl complexes are responsible for some of their biological activities and that this mechanism may be involved in S-nitrosothiol-signalling reactions.


Editorial on S.I. "Advances in Measuring Health and Wellbeing" in the International Journal of Environmental Research and Public Health.
Measuring the health and wellbeing of the population is the first step in visualizing the real needs of the population in order to promote healthy habits, as well as effective health and social policy responses [...].


Idiopathic left ventricular aneurysm: an unusual substrate of ventricular fibrillation and ventricular tachycardia.
Idiopathic left ventricular aneurysm (LVA) is a very rare clinical condition. This article describes a patient with idiopathic LVA associated with episodes of ventricular tachycardia and ventricular fibrillation. Clinical and instrumental examinations did not reveal the pathogenesis of the aneurysm. The malignant clinical course suggests that an aggressive antiarrhythmic treatment, including ICD implantation, may be warranted.


Modulating circulating sFlt1 in an animal model of preeclampsia using PAMAM nanoparticles for siRNA delivery.
Excessive circulating sFlt1 plays a major role in the pathogenesis of preeclampsia (PE). Using RNAi to silence sFlt1 may be a therapy for treating PE. Because of the rapid degradation of siRNA, gene therapy in vivo remains limited. Poly-amidoamine (PAMAM) has been demonstrated to be an excellent nanocarrier for siRNA delivery with no discernible toxicity. The aim of the present study was to investigate the therapeutic effect of siRNA-sFlt1-PAMAM on PE. The biophysical properties of siRNA-sFlt1-PAMAM complexes were analysed. Next, HTR-8/SVneo cells were incubated with the complexes. The transfection efficiency, silencing effect, and cell proliferation were examined. The timed pregnant rats were grouped to test the in vivo effect of siRNA-sFlt1-PAMAM on PE. The PE model was established by injection of tumour necrosis factor-α (TNF-α), while treatment group rats were injected with both TNF-α and siRNA-sFlt1-PAMAM. The mean arterial pressure, serum levels of sFlt1, and 24-h urinary protein were measured. The number of viable pups, and weights of individual pups and placentae were determined. siRNA-sFlt1-PAMAM complexes showed high cellular uptake and excellent siRNA encapsulation ability. siRNA-sFlt1-PAMAM significantly decreased sFlt1 secretion from HTR-8/SVneo cells (p = 0.001) with little effect on HTR-8/SVneo cell proliferation. The circulating level of sFlt1, mean arterial pressure, and urine protein level in the TNF-α group were significantly increased compared to that in the control group, while the weights of foetuses and placentae were significantly decreased compared to that in the control group (p < 0.05). All preeclamptic symptoms were greatly attenuated by siRNA-sFlt1-PAMAM (p < 0.05). These data suggest that siRNA-sFlt1-PAMAM effectively decreased sFlt1 secretion and improved pregnancy outcomes in a preeclamptic rat model, which may provide a new therapeutic strategy for PE.


Safety and efficacy of prophylactic tirofiban infusion for acute intracranial intraprocedural stent thrombosis.
Periprocedural antithrombotic management with glycoprotein IIb/IIIa inhibitors (GPI) for intracranial artery stenting is still controversial. We sought to assess the safety and efficacy of prophylactic tirofiban infusion for acute intracranial intraprocedural stent thrombosis in routine clinical practice. From January 2013 to December 2019, consecutive patients treated with endovascular stenting for symptomatic intracranial atherosclerotic stenosis (ICAS) were identified and dichotomized by whether tirofiban was used. The efficacy and safety outcomes were compared by propensity score matching. A total of 160 consecutive patients in the tirofiban group and 177 patients in the non-tirofiban group were enrolled. Propensity score matching analysis selected 236 matched patients. One acute intraprocedural stent thrombosis (AIST) occurred in patients receiving prophylactic tirofiban, while 8 in the non-tirofiban group. The incidence of AIST in the tirofiban group was significantly lower than that in the non-tirofiban group (0.8% vs 6.8%, P = 0.039). The periprocedural ischemic events (8.5% vs 5.1%, P = 0.424), periprocedural intracranial hemorrhage (4.2% vs 0.8%, P = 0.219) and 30-day total mortality (3.4% vs 0%, P = 0.125) were not statistically different between the two groups. Compared with conventional stenting angioplasty without tirofiban, tirofiban prophylactic infusion can lower the incidence of AIST, without increasing the risk of periprocedural intracranial hemorrhage and 30-day total mortality. However, there is no superiority in reducing periprocedural ischemic events. The current study adds more important insights to the available clinical evidence on the use of tirofiban during stenting of ICAS.


[Neurophysiological monitoring options in brain tumour resections. Consensus statement from the Spanish Society of Neurosurgery's (SENEC) Neuro-oncology Working Group and the Spanish Society of Clinical Neurophysiology (SENFC)].
Brain tumours located in or in proximity to eloquent areas are a significant neurosurgical challenge. Performing this kind of surgery with neurophysiological monitoring to improve resections with reduced permanent focal neurological deficit has become widely accepted in the literature. However, how to conduct this monitoring, the exact definition of an eloquent area and whether to perform this surgery with the patient awake or asleep are still subject to rigorous scientific debate. Members of the Neuro-oncology Working Group (GTNO) of the Spanish Society of Neurosurgery (SENEC) and members of the Spanish Society of Clinical Neurophysiology (SENFC) have published a consensus statement to explain the different neurophysiological monitoring options currently available in awake and asleep patients to obtain better surgical resection without neurological deficits. An exhaustive review of the literature has also been conducted.


Electromagnetic field change the expression of osteogenesis genes in murine bone marrow mesenchymal stem cells.
In order to identify the differentially expressing gene of bone marrow mesenchymal stem cells (MSCs) stimulated by electromagnetic field (EMF) with osteogenesis microarray analysis, the bone marrow MSCs of SD rats were isolated and cultured in vitro. The third-passage cells were stimulated by EMFs and total RNA was extracted, purified and then used for the synthesis of cDNA and cRNA. The cRNA of stimulated group and the control group was hybridized with the rat oligo osteogenesis microarray respectively. The hybridization signals were acquired by using X-ray film after chemiluminescent detection and the data obtained were analyzed by employing the web-based completely integrated GEArray Expression Analysis Suite. RT-PCR was used to identify the target genes: Bmp1, Bmp7, Egf and Egfr. The results showed that 19 differentially expressing genes were found between the stimulated group and the control group. There were 6 up-regulated genes and 13 down-regulated genes in the stimulated group. Semi-quantitative RT-PCR confirmed that the expressions of Bmp1, Bmp7 mRNA of the stimulated group were up-regulated (P<0.05) and those of Egf, Egfr were down-regulated (P<0.05). It was suggested that the gene expression profiles of osteogenesis of the bone marrow MSCs were changed after EMF treatment. It is concluded that the genes are involved in skeletal development, bone mineral metabolism, cell growth and differentiation, cell adhesion etc.


Identification of hyperactive intrinsic amygdala network connectivity associated with impulsivity in abstinent heroin addicts.
Impulsivity is a pathological hallmark of drug addiction. However, little is known about the neuropsychological underpinnings of this impaired impulsive control network on drug addiction. Twenty two abstinent heroin dependent (HD) subjects and 15 cognitively normal (CN) subjects participated in this study. Resting-state functional connectivity MRI was employed to measure abnormalities in the intrinsic amygdala functional connectivity (iAFC) network activity and the Barratt Impulsive Scale, 11th version was used to measure impulsivity. Linear regression analysis was applied to detect the neural constructs underlying impulsivity by correlating iAFC network activity with impulsive scores. In the HD group, higher impulsivity scores and significantly enhanced iAFC network activity were found, especially in bilateral thalamus, right insula, and inferior frontal gyrus. Markedly decreased anticorrelated iAFC network activity was seen in the left precuneus, and even switched to positive correlation pattern in right precuneus, relative to the CN group. The iAFC network strengths in the HD group were positively correlated with impulsivity in the right subcallosal gyrus, insula, thalamus and posterior cingulate cortex, and negatively correlated in left fusiform area. In the CN group, the left pre-somamotor area-amygdala connectivity was positively correlated, and right orbital frontal cortex-amygdala and precuneus-amygdala connectivity were negatively correlated with impulsivity scores. Our study demonstrates different constructs of the impulsive network in HD and CN subjects. Altered iAFC network connectivity in HD subjects may contribute to the loss of impulsive control. This further facilitates our understanding of the neural underpinnings of behavior dysfunction in addiction.


The burden of atrial fibrillation and heart failure in hospitalized patients: A real-world survey in a nationwide snapshot.
Atrial fibrillation (AF) and heart failure (HF) are common and commonly coexisting cardiovascular diseases in hospitalized patients. We report the absolute number and interrelation between AF and HF, assess the daily burden of both diseases on the healthcare system, and describe the medical treatment in a real-world, nationwide conducted snapshot survey. A questionnaire was equally distributed to various healthcare institutions. Data on the baseline characteristics, prior hospitalizations, and medical treatments of all hospitalized patients with AF and HF at a predefined date were collected and analyzed. Seventy-five cardiological departments participated in this multicenter Greek nationwide study. A total of 603 patients (mean age, 74.5 ± 11.4 years) with AF, HF, or the combination of both were nationwide admitted. AF, HF, and the combination of both were registered in 122 (20.2%), 196 (32.5%), and 285 (47.3%) patients, respectively. First-time hospital admission was recorded in 273 (45.7%) of 597 patients, whereas 324 (54.3%) of 597 patients had readmissions in the past 12 months. Of the entire population, 453 (75.1%) were on beta-blockers (BBs), and 430 (71.3%) were on loop diuretics. Furthermore, 315 patients with AF (77.4%) were on oral anticoagulation, of whom 191 (46.9%) were on a direct oral anticoagulant and 124 (30.5%) were on a vitamin K antagonist. Hospitalized patients with AF and/or HF have more than one admission within a year. Coexistence of AF and HF is more common. BBs and loop diuretics are the most commonly used drugs. More than three-quarters of the patients with AF were on oral anticoagulation.


Lactate threshold and onset of blood lactate accumulation during incremental exercise after dietary modifications.
This study was designed to clarify the effects of dietary modifications on the lactate threshold (LT) and on the onset of blood lactate accumulation (OBLA) during progressive incremental exercise. Six healthy males volunteered for the study. Informed consent was obtained from every participant. The following protocol was administered to each subject on three occasions: a 48-h period of mixed dieting (53% carbohydrates, 30% lipids, 17% proteins) preceding the first exercise test, immediately followed by a 48-h period of either a carbohydrate-rich (68% CHO, 23% lipids, 9% proteins) or a fat-rich (19% CHO, 57% lipids, 26% proteins) iso-caloric diet leading to the second exercise and separated from the third test by a 12-days period. Exercise tests were conducted on an electrically-braked ergocycle, and consisted of a progressive incremental maximal exercise. Respiratory parameters were continuously monitored by an automated open circuit sampling system. Exercise blood lactate (LA), free fatty acids (FFA), glucose levels and acid-base balance were determined from venous blood samples obtained through an indwelling brachial catheter. Peak lactate values, workload and performance time were not significantly altered by imposed diets. Furthermore, dietary modifications had no significant effect on LT, OBLA fixed at 4 mmol and ventilatory threshold. Increased pH and FFA mobilization were observed with fat-rich diet, while CHO-rich diet markedly increased the respiratory exchange ratio (R). It is concluded that LT and OBLA are not significantly altered by fat or CHO enrichment of diets.


Mobilization of a diatom mutator-like element (MULE) transposon inactivates the uridine monophosphate synthase (UMPS) locus in Phaeodactylum tricornutum.
Diatoms are photosynthetic unicellular microalgae that drive global ecological phenomena in the biosphere and are emerging as sustainable feedstock for an increasing number of industrial applications. Diatoms exhibit enormous taxonomic and genetic diversity, which often results in peculiar biochemical and biological traits. Transposable elements (TEs) represent a substantial portion of diatom genomes and have been hypothesized to exert a relevant role in enriching genetic diversity and making a core contribution to genome evolution. Here, through long-read whole-genome sequencing, we identified a mutator-like element (MULE) in the model diatom Phaeodactylum tricornutum, and we report the direct observation of its mobilization within the course of a single laboratory experiment. Under selective conditions, this TE inactivated the uridine monophosphate synthase (UMPS) gene of P. tricornutum, one of the few endogenous genetic loci currently targeted for selectable auxotrophy for functional genetics and genome-editing applications. We report the observation of a recently mobilized transposon in diatoms with unique features. These include the combined presence of a MULE transposase with zinc-finger SWIM-type domains and a diatom-specific E3 ubiquitin ligase of the zinc-finger UBR type, which are suggestive of a mobilization mechanism. Our findings provide new elements for the understanding of the role of TEs in diatom genome evolution and in the enrichment of intraspecific genetic variability.


Midazolam for induction of anaesthesia in patients with limited cardiac reserves. A comparison with etomidate.
The new water-soluble benzodiazepine, midazolam (Dormicum; Roche), was compared with etomidate as part of a balanced technique for induction of anaesthesia in 16 patients undergoing cardiac valve replacement. Monitoring revealed a significantly greater fall in blood pressure in patients receiving midazolam (reaching dangerous levels in 2 patients), which suggests that this agent is not suitable for induction of anaesthesia in haemodynamically compromised patients.


[Immunocytochemical localization of the GFAP in heterotransplanted human gliomas (author's transl)].
Three cell lines derived in our laboratory from human malignant gliomas (SA 130, SA 132, SA 134) were injected subcutaneously into pathogen-free nude thymus less mice. These three cell lines gave origine to malignant tumors which, as original tumors, were positive for the glial fibrillary acidic protein (GFAP) revealed by immunoperoxidase method.


The effect of temperature on the QTc interval in the newborn infant receiving extracorporeal membrane oxygenation (ECMO).
To explore the changes in the QTc interval during mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). Twenty seven neonates (median gestation 40 weeks; range 33-41 weeks) enrolled in a pilot study of mild hypothermia were studied during the first five days of ECMO. The first group (N=7) were maintained at 37 degrees C throughout the study period. Subsequent groups (N=5) were cooled to 36 degrees C, 35 degrees C and 34 degrees C respectively for twenty four hours and the final group to 34 degrees C for forty eight hours before being rewarmed to 37 degrees C. Using a 24 h digital monitor, the QT and QTc intervals were recorded continuously during the cooling and rewarming period and validated using standard 12 lead electrocardiograms. Patients were carefully assessed clinically and routine biochemistry (including magnesium and calcium) laboratory tests measured pre ECMO and at timed intervals during cooling and rewarming. The mean difference between the continuous digital and 12 lead ECG values for QTc was -13.3 ms. During the first 24 h of cooling, the mean (95th centile) values for the digitally measured QTc interval at 37 degrees C=431(506) milliseconds (ms); 36 degrees C=459(521) ms; 35 degrees C=445(516) ms; 34 degrees C=465(531) ms; 34 degrees C for 48 h=466(521) ms. During this period overall QTc increased by 3.12 ms (95% confidence intervals 6.17 to 0.84; p=0.04) for each degree fall in body temperature. During rewarming, there was no significant relationship between QTc and temperature change. No serious arrhythmias were during cooling. Using univariate analysis, no relationship was found between QTc and electrolytes, heart rate and blood pressure. QTc shows significant variability in individuals, and only a small proportion of this can be explained by rectal temperature. Mild hypothermia was not associated with serious cardiac arrhythmias.


Competency Assessment for Mediastinal Mass Resection and Thymectomy: Design and Delphi Review Process.
Mediastinal mass resection and thymectomy are complex and related operations that are core components of competency for a general thoracic surgeon and an important learning objective for thoracic surgery trainees. This study aimed to design a combined competency assessment instrument for mediastinal mass resection and thymectomy. A comprehensive competency assessment instrument was designed by a process of logical analysis by 3 expert thoracic surgeons with an interest in mediastinal surgery. The instrument was then assessed and refined using a modified Delphi process. The Delphi questionnaire was distributed to all members of the Canadian Association of Thoracic Surgeons in 2018 to 2019. The first round of the Delphi review was completed by 58 respondents (response rate 43.9%). Respondents represented all Canadian provinces with a wide range of clinical experience and a high rate of involvement in resident education. A first draft of the competency assessment instrument included 42 steps in 6 categories. A total of 3 rounds of Delphi review were performed. Cronbach's alpha for the final round was 0.83. Ultimately, 29 items were retained from the original instrument and two modified and three new items were added. The final instrument has 34 steps in 5 categories. A nationwide consensus was established on the key components of assessing competence to perform mediastinal mass resection and thymectomy. The resulting instrument could be used to guide competency based assessments of thoracic surgeons and trainees.


National Trends and Predictors of Organ-sparing for Invasive Penile Tumors: Expanding the Therapeutic Window.
The purpose of this study was to analyze contemporary trends and predictors in the use of organ-sparing treatment (OST) for low-stage invasive penile tumors as well as to ascertain its impact on overall mortality (OM) in those with high-risk (pT2) disease. The National Cancer Data Base was queried for patients with clinically nonmetastatic penile cancer and available pathologic tumor (pT) and treatment data from 1998 to 2012. Independent predictors for performance of OST were analyzed. Multivariable Cox proportional hazard regression was used to identify factors of OM in a subset of patients with pT2 disease. A total of 4231 patients with ≤ pT2cN0cM0 primary penile cancer were identified over a median follow-up of 39.6 months. Approximately 49% of patients received OST over the study period (P = .009). Older age, Hispanic ethnicity, urban counties, academic facilities, and pT2 disease were negative predictors for OST (all P < .05), whereas grade and years of diagnosis where associated with increased performance (P < .01). In subgroup analysis of pT2 patients, older age, black race, comorbidity, node status, and grade were associated with higher OM (all P < .05). When compared with radical penectomy, partial penectomy was associated with decreased OM (hazard ratio, 0.67; 95% confidence interval, 0.52-0.87; P = .002), whereas organ-sparing did not affect survival (hazard ratio, 0.83; 95% confidence interval, 0.52-1.31; P = .419) in these patients. Ethnic and socioeconomic differences exist in the local management of penile tumors. No impact on OM was observed for those with high-risk cases treated with organ-sparing at intermediate follow-up. More studies are needed to evaluate oncologic efficacy of organ-sparing in carefully selected invasive penile tumors.


Factors associated with endometrial cancer and hyperplasia among middle-aged and older Hispanics.
While disparities in endometrial hyperplasia and endometrial cancer are well documented in Blacks and Whites, limited information exists for Hispanics. The objective is to describe the patient characteristics associated with endometrial hyperplasia symptoms, endometrial hyperplasia with atypia and endometrial cancer, and assess factors contributing to racial/ethnic differences in disease outcomes. This single-center, retrospective study included women aged ≥50 years with ≥ two encounters for endometrial hyperplasia symptoms, endometrial hyperplasia with atypia and endometrial cancer between 2012 and 2016. Multivariate logistic regression models evaluated the predictors of endometrial cancer and hyperplasia. We included 19,865 women (4749 endometrial hyperplasia symptoms, 71 endometrial hyperplasias with atypia, 201 endometrial cancers) with mean age of 60.45 years (SD 9.94). The odds of endometrial hyperplasia symptoms were higher in non-Hispanic Blacks (Odds Ratio [OR] 1.56, 95% Confidence Interval [CI] 1.20-1.72), Hispanics (OR 1.35, 95% CI 1.22-1.49), family history of female cancer (OR 1.25, 95% CI 1.12-1.39), hypertension (OR 1.24, 95% CI 1.14-1.35), and birth control use (OR 1.29, 95% CI 1.15-1.43). Odds of endometrial cancer and atypical hyperplasia increased for ages 60-64 (OR 7.95, 95% CI 3.26-19.37; OR 3.66, 95% 1.01-13.22) and being obese (OR 1.61, 95% CI 1.08-2.41; OR: 6.60, 95% CI 2.32-18.83). Odds of endometrial cancer increased with diabetes (OR 1.68, 95% CI 1.22-2.32). Patients with obesity and diabetes had increased odds of endometrial cancer and hyperplasia with atypia. Further study is needed to understand the exogenous estrogen effect contributing to the increased incidence among Hispanics.


Membranes of MnO Beading in Carbon Nanofibers as Flexible Anodes for High-Performance Lithium-Ion Batteries.
Freestanding yet flexible membranes of MnO/carbon nanofibers are successfully fabricated through incorporating MnO2 nanowires into polymer solution by a facile electrospinning technique. During the stabilization and carbonization processes of the as-spun membranes, MnO2 nanowires are transformed to MnO nanoparticles coincided with a conversion of the polymer from an amorphous state to a graphitic structure of carbon nanofibers. The hybrids consist of isolated MnO nanoparticles beading in the porous carbon and demonstrate superior performance when being used as a binder-free anode for lithium-ion batteries. With an optimized amount of MnO (34.6 wt%), the anode exhibits a reversible capacity of as high as 987.3 mAh g(-1) after 150 discharge/charge cycles at 0.1 A g(-1), a good rate capability (406.1 mAh g(-1) at 3 A g(-1)) and an excellent cycling performance (655 mAh g(-1) over 280 cycles at 0.5 A g(-1)). Furthermore, the hybrid anode maintains a good electrochemical performance at bending state as a flexible electrode.