Comparative proteomic analysis of midgut proteins from male and female Bombyx mori (Lepidoptera: Bombycidae).
Many biological phenotypes of male and female silkworms (Bombyx mori) are quite different, and one of the major differences is the growth rate at various larval stages. Nutrient utilization by midgut varies with sexes. However, the molecular basis of this variation is not clear. To understand the molecular mechanism, comparative proteomic approach was employed to investigate the variation of midgut proteomes between male and female silkworms. Totally, 32 proteins that were grouped into four categories were differentially expressed and subsequently identified by mass spectrometry. Gene ontology analysis revealed that these proteins were attributed with biological functions such as binding, catalytic, and transporter, and these proteins were involved in biological process such as cellular process, localization, and metabolic process. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these proteins were involved in pathways such as glycolysis, gluconeogenesis, oxidative phosphorylation, and purine metabolism. At transcription level, the expressional variation was confirmed for six identified proteins including muscle glycogen phosphorylase, uridine 5'-monophosphate synthase, cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha, ATP synthase, thiol peroxiredoxin, and serpin-2. This study provides useful information for understanding the mechanisms of nutrient absorption and the protein-protein interaction in the silkworm.


Creating a Radiology Quality and Safety Program: Principles and Pitfalls.
All radiology departments are now expected to create organized and comprehensive quality and safety (QS) programs. No matter the department size, there are fundamental principles that should be at the core of each program. "Just culture" and culture of safety are essential principles in establishing effective programs. Physician leaders of QS programs must involve stakeholders, define program goals, and develop an effective program structure. QS programs should establish reliable quality assurance and patient safety systems. Integrating continuous quality improvement and learning into the department and prioritizing patient and referring clinician experiences will enhance outcomes. Physician QS leaders will face common obstacles in program development and management. Heightened awareness of these obstacles and understanding potential solutions will help programs succeed. Leveraging resources offered by professional societies and engaging in radiology QS community networks will provide ongoing support for program leaders. ©RSNA, 2018.


American Society of Clinical Oncology (ASCO) - 55th Annual Meeting (May 31-June 4, 2019 - Chicago, Illinois, USA).
The theme for this year's meeting of the American Association of Clinical Oncology (ASCO) was 'Caring for Every Patient, Learning from Every Patient'. The meeting consisted of oral, plenary and educational sessions, as well as poster presentations and discussions about important topics in the field of oncology, such as precision medicine, the latest in cancer research impacting patient care, new treatment options and insights for improving access to care. This 55th ASCO annual meeting was held from May 31 to June 4 in Chicago, Illinois, and was attended by over 40,000 cancer experts from around the world who followed a robust program providing opportunities to teach, engage and, most importantly, bring the oncology field together with the aim of improving care for patients with a cancer diagnosis. This report covers some of the later-stage developments and results presented at the meeting.


[Microclimatic conditions in medium-power plants and their effect on the human body].
The paper presents microclimatic conditions in a room of one of the power stations in the Upper-Silesian Industrial Region. Particularly strenuous, especially during summer, appeared to be the high air and radiant temperatures near ( boilers and furnaces), accompanied by considerable noise intensity. In addition, measurements and chemical analyses of airborne dust have been taken, and those did not demonstrate any significant risk to workers. Yet, the content of tar substances in dusts, including aromatic polycyclic hydrocarbons, potentially exposes workers to mutagenic and carcinogenic effects. Experimental studies on animals showed also coniogenic effects of airborne-ashes. Permanent exposure to toxic metals found in dusts as well as in workers blood and urine may induce metabolic disorders.


[The absence of stewardship in the Chilean health authority after the 2004 health reform].
Stewardship is the most important political function of a health system. It is a government responsibility carried out by the health authority. Among other dimensions, it is also a meta-function that includes conduction and regulation. The Health Authority and Management Act, which came about from the health reform of 2004, separated the functions of service provision and stewardship with the aim of strengthening the role of the health authority. However, the current structure of the health system contains overlapping functions between the different entities that leads to lack of coordination and inconsistencies, and a greater weight on individual health actions at the expense of collective ones. Consequently, a properly funded national health strategy to improve the health of the population is missing. Additionally, the components of citizen participation and governance are weak. It is necessary, therefore, to revisit the Chilean health structure in order to develop one that truly enables the exercise of the health authority's stewardship role.


Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose.
The purpose of this study was to determine the tissue and corresponding serum concentration of tigecycline at selected time points in gall bladder, bile, colon, bone, synovial fluid (SF), lung and CSF in subjects undergoing surgical or medical procedures. One hundred and four adult subjects (aged 24-83 years; 64 women, 40 men) received a single intravenous (i.v.) dose of tigecycline (100 mg infused over 30 min). Subjects were randomly assigned to one of four collection times at 4, 8, 12 and 24 h after the start of the infusion. For CSF, samples were collected at approximately 1.5 and 24 h after the start of the infusion. All subjects had serum samples collected before the administration of tigecycline, at the end of the infusion and at the time corresponding to tissue or body fluid collection. Drug concentrations in serum, tissues and body fluids were determined by LC/MS/MS. The area under the mean concentration-time curve from 0 to 24 h (AUC(0-24)) was determined for the comparison of systemic exposure between tissue or body fluid to serum. The mean serum concentrations of tigecycline were similar to those previously published. Tissue penetration, expressed as the ratio of AUC(0-24) in tissue or body fluid to serum, was 537 for bile, 23 for gall bladder, 2.6 for colon, 2.0 for lung, 0.41 for bone, 0.31 for SF and 0.11 for CSF. A single 100 mg dose of intravenous tigecycline produced considerably higher tissue/fluid concentrations in bile, gall bladder, colon and lung compared with simultaneous serum concentrations. On average, the systemic exposure of tigecycline in bone, SF and CSF ranged from 11% to 41% of serum concentrations. The results in bone are inconsistent with previous radiolabelled studies in animals and it is unclear if tight binding to bone (versus low bone uptake) or poor extraction of tigecycline for LC/MS/MS detection or both may have contributed to the differences we observed in humans.


Efficacy and tolerability of Lavandula angustifolia in treating patients with the diagnosis of depression: a systematic review of randomized controlled trials.
Pharmacotherapy is the conventional treatment for depression, with only half of the patients responding to the first trial of monotherapy with first-line medicines. One way to overcome this resistance is to use complementary and alternative medicine. The antidepressant effects of Lavandula angustifolia, which is commonly called lavender, have been investigated in previous studies. This study aims to provide the first systematic review of lavender in treating patients with depression diagnosis. ISI Web of Science, Scopus, PubMed, Embase, PsycINFO, Google Scholar, and three trial registries were searched until May 2020 to find randomized controlled trials on lavender for depressed patients. The primary outcome was difference between the intervention and control groups in changing depression scores from baseline to endpoint. The included studies were assessed for effect size and methodological quality. Seven clinical trials were identified, in which 852 patients were studied. In six trials, the effectiveness of lavender in treating depression was reported, as being more pronounced adjunct to a typical antidepressant in one study. Significant reported side effects include headaches and eructation. Lavender is beneficial, tolerable, and safe in treating depression. Despite obtaining promising results, they are not enough to recommend prescribing lavender to depressed patients. Further high-quality, large-scale studies for rectifying the shortcomings of existing studies are recommended.


Heteromeric amino acid transporters. In search of the molecular bases of transport cycle mechanisms.
Heteromeric amino acid transporters (HATs) are relevant targets for structural studies. On the one hand, HATs are involved in inherited and acquired human pathologies. On the other hand, these molecules are the only known examples of solute transporters composed of two subunits (heavy and light) linked by a disulfide bridge. Unfortunately, structural knowledge of HATs is scarce and limited to the atomic structure of the ectodomain of a heavy subunit (human 4F2hc-ED) and distant prokaryotic homologues of the light subunits that share a LeuT-fold. Recent data on human 4F2hc/LAT2 at nanometer resolution revealed 4F2hc-ED positioned on top of the external loops of the light subunit LAT2. Improved resolution of the structure of HATs, combined with conformational studies, is essential to establish the structural bases for light subunit recognition and to evaluate the functional relevance of heavy and light subunit interactions for the amino acid transport cycle.


An enigmatic long-lasting gamma-ray burst not accompanied by a bright supernova.
Gamma-ray bursts (GRBs) are short, intense flashes of soft gamma-rays coming from the distant Universe. Long-duration GRBs (those lasting more than approximately 2 s) are believed to originate from the deaths of massive stars, mainly on the basis of a handful of solid associations between GRBs and supernovae. GRB 060614, one of the closest GRBs discovered, consisted of a 5-s hard spike followed by softer, brighter emission that lasted for approximately 100 s (refs 8, 9). Here we report deep optical observations of GRB 060614 showing no emerging supernova with absolute visual magnitude brighter than M(V) = -13.7. Any supernova associated with GRB 060614 was therefore at least 100 times fainter, at optical wavelengths, than the other supernovae associated with GRBs. This demonstrates that some long-lasting GRBs can either be associated with a very faint supernova or produced by different phenomena.


Chondrotinase ABC I thermal stability is enhanced by site-directed mutagenesis: a molecular dynamic simulations approach.
Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of growth in the adult central nervous system. Use of the enzyme chondroitinase ABC I (ChABC I) as a strategy to reduce CSPG inhibition in experimental models of spinal cord injury has led to observations of its remarkable capacity for repair. More importantly, ChABC therapy has been demonstrated to promote significant recovery of function to spinal injured animals. Despite this incomparable function of ChABC I, its clinical application has been limited because of its thermal instability as reported in the literature. In a recent study by Nazari-Robati et al., thermal stability of ChABC I was improved by protein engineering using site-directed mutagenesis method. Here, in this study, molecular dynamics simulations were used to take a closer look into the phenomenon leading to the experimentally observed thermal stability improvement followed by the corresponding site-directed mutagenesis. We concluded that the mutations induce local flexibility along with a re-conformation into the native structure which consequently increase the protein thermal stability.


[Giant hepatic echinococcus cyst with cysto-pleural fistula and pleural echinococcosis].
Extrahepatic complications from hepatic cystic echinococcosis are rare and may be life threatening. Although the prevalence of echinococcosis in Spain had decreased, the number of cases of this disease and its severity has risen again due to immigration. We report the case of a patient with a giant hepatic echinococcus cyst diagnosed during investigation of an abdominal mass. The mass was associated with three other cysts: the first cyst was fistulized to the biliary tract, without clinical or laboratory alterations, the second cyst was fistulized to the right pleural cavity, leading to pleural echinococcosis and respiratory distress due to massive pleural effusion, and the third cyst was calcified. The challenge in this case layed in its diagnosis and treatment. The clinical presentation was unusual due to the extension of the disease, hampering complete cystic excision.


Voiding dysfunction after repair of giant trigonal vesicovaginal or urethrovesicovaginal fistulae: A need for long-term follow-up.
Urodynamic findings of lower urinary tract of women presenting with voiding dysfunction after successful repair of complex trigonal vesicovaginal fistulas at our institute are presented. In this retrospective case series, women presenting with voiding dysfunction after successful repair of obstetric fistulae were evaluated. In addition of standard clinical evaluation with history and clinical examination, all underwent kidney-ureter-bladder ultrasonography, renal function test, urine culture, and multichannel urodynamics. The latter consisted of free uroflowmetry, filling and voiding cystometry. Five women (median age 35 years; range 30-45) presented with difficulty in voiding after the successful repair; two presented within 1 year and 3 after 10 years. The latter three presented with bilateral hydroureteronephrosis; one of these had chronic kidney disease (CKD) grade IV at presentation. Urodynamics (UDS) of all patients revealed poor detrusor compliance (median 11 ml/cm H2O; range 5-22), high-end filling detrusor pressures (median 41 cm H2O; range 11-46) and no detrusor overactivity. All patients attempted voiding with abdominal straining; with little contribution of detrusor contraction (median 6 cm H2O; range 0-9). Two patients could not void during the study, one with Tanagho reconstruction and another with CKD. Even after successful repair, patients with complex trigonal or urethra-vesicovaginal fistulae warrant indefinite long-term follow-up for voiding dysfunction in view of possibility of developing poorly compliant bladder.


Co-activation of saphenous nerve fibers: a potential therapeutic mechanism of percutaneous tibial nerve stimulation?
Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive and effective treatment for overactive bladder (OAB). However, clinical trials show that positive therapeutic outcomes among patients are difficult to predict (failure rate = 35% to 50%). Inconsistencies in the stimulation amplitudes used clinically and those used in preclinical animal studies led us to hypothesize that OAB therapy involves a secondary bladder-inhibitory pathway. In this paper, we implemented and tested a computer model of the human lower leg that investigated the differential activation of the saphenous nerve (SAFN) and tibial nerve (TN) during percutaneous electrical stimulation. Our preliminary findings show that concomitant activation of SAFN branches occurs during PTNS, which suggests the possibility that the SAFN may influence the clinical outcome of treatment.


Detection of ampicillin resistant Haemophilus influenzae in United Kingdom laboratories.
Susceptibility of Haemophilus influenzae clinical isolates to ampicillin reported by 23 laboratories, using a variety of methods, was compared with results obtained following retesting at The London Hospital Medical College. Beta lactamase production was not detected on initial isolation in 25 of 157 isolates (16%) found to be positive on retest. One hundred beta lactamase negative isolates, which gave reduced zone diameters (less than 20 mm) around 2 micrograms discs and required 1-64 mg/l ampicillin for inhibition, were detected at The London Hospital. Eighty five of these had been reported as sensitive to ampicillin by the laboratories of origin. Many of these 100 isolates showed reduced susceptibility to other beta lactam antibiotics. Accurate detection of non-enzymic reduced susceptibility to ampicillin may emerge as an important guide to the likely sensitivity of H influenzae isolates to the enzyme stable beta lactams.


A Rare Multilevel Spinal Epidural Abscess With Streptococcus agalactiae in an Adult With Uncontrolled Diabetes: A Case Report.
Spinal epidural abscess (SEA) is a rare, life-threatening infection that typically presents with fever, back pain, and neurologic deficits. Although most commonly caused by Staphylococcus aureus, this case reviews a rare occurrence of a multilevel SEA caused by Streptococcus agalactiae in a 62-year-old female with uncontrolled type II diabetes mellitus. The patient initially presented with lower back pain and was subsequently diagnosed with a SEA complicated by hyperglycemia. A prompt diagnosis with magnetic resonance imaging (MRI) revealed extensive abscess formation, leading to emergent neurosurgical intervention. Streptococcus agalactiae was identified as the causative organism through culture. The report emphasizes the challenges of early detection of SEA and highlights the importance of considering unusual pathogens in high-risk patients. Timely management is crucial to prevent permanent neurologic deficits and to achieve favorable outcomes.


Robust superhydrophobic mats based on electrospun crystalline nanofibers combined with a silane precursor.
We demonstrate the fabrication of solvent-resistant, mechanically robust, superhydrophobic nanofibrous mats by electrospinning of poly(vinylidene fluoride) (PVDF) in the presence of inorganic silane materials. The solvent resistance and mechanical strength of nanofibrous mats were dramatically increased through the crystallization of as-spun PVDF fibers or incorporation of a tetraethyl orthosilicate (TEOS) sol into the nanofibrous matrix. The electrospun nanofibrous mats yielded a water contact angle of 156 degrees that did not vary with TEOS content. The solvent resistance and mechanical robustness of the electrospun mats were significantly enhanced through extensive cross-linking of TEOS, even after short PVDF annealing times. The interpenetrating polymer network, which embeds polymer chains in a TEOS network, allows the fabrication of robust functional nanofibers by combining semicrystalline polymers with electrospinning techniques.


Polycaprolactone Nanofibers Containing Vascular Endothelial Growth Factor-Encapsulated Gelatin Particles Enhance Mesenchymal Stem Cell Differentiation and Angiogenesis of Endothelial Cells.
During the regeneration of tissues and organs, growth factors (GFs) play a vital role by affecting cell behavior. However, because of the low half-life time and quick degradation of GFs, their stimulations on cells are relatively short and discontinuous. In this study, a releasing scaffold platform, consisting of polycaprolactone (PCL) nanofibers and vascular endothelial growth factor (VEGF)-encapsulated gelatin particles, was developed to extend the influence of GFs on mesenchymal stem cells (MSCs) and endothelial cells (ECs). The results showed that this kind of scaffold can direct the differentiation of MSCs to ECs and maintain the stability of the tubular structure, an indicator of the angiogenesis ability of ECs, for an extended period of time. Therefore, the results suggest the potential application of PCL/VEGF-encapsulated gelatin particles (PCL/VGPs) as a growth factor (GF)-releasing scaffold platform in vascular tissue engineering.


Circulating acylcarnitine profile in human heart failure: a surrogate of fatty acid metabolic dysregulation in mitochondria and beyond.
Heart failure (HF) is associated with metabolic perturbations, particularly of fatty acids (FAs), which remain to be better understood in humans. This study aimed at testing the hypothesis that HF patients with reduced ejection fraction display systemic perturbations in levels of energy-related metabolites, especially those reflecting dysregulation of FA metabolism, namely, acylcarnitines (ACs). Circulating metabolites were assessed using mass spectrometry (MS)-based methods in two cohorts. The main cohort consisted of 72 control subjects and 68 HF patients exhibiting depressed left ventricular ejection fraction (25.9 ± 6.9%) and mostly of ischemic etiology with ≥2 comorbidities. HF patients displayed marginal changes in plasma levels of tricarboxylic acid cycle-related metabolites or indexes of mitochondrial or cytosolic redox status. They had, however, 22-79% higher circulating ACs, irrespective of chain length (P < 0.0001, adjusted for sex, age, renal function, and insulin resistance, determined by shotgun MS/MS), which reflects defective mitochondrial β-oxidation, and were significantly associated with levels of NH2-terminal pro-B-type natriuretic peptide levels, a disease severity marker. Subsequent extended liquid chromatography-tandem MS analysis of 53 plasma ACs in a subset group from the primary cohort confirmed and further substantiated with a comprehensive lipidomic analysis in a validation cohort revealed in HF patients a more complex circulating AC profile. The latter included dicarboxylic-ACs and dihydroxy-ACs as well as very long chain (VLC) ACs or sphingolipids with VLCFAs (>20 carbons), which are proxies of dysregulated FA metabolism in peroxisomes. Our study identified alterations in circulating ACs in HF patients that are independent of biological traits and associated with disease severity markers. These alterations reflect dysfunctional FA metabolism in mitochondria but also beyond, namely, in peroxisomes, suggesting a novel mechanism contributing to global lipid perturbations in human HF.NEW & NOTEWORTHY Mass spectrometry-based profiling of circulating energy metabolites, including acylcarnitines, in two cohorts of heart failure versus control subjects revealed multiple alterations in fatty acid metabolism in peroxisomes in addition to mitochondria, thereby highlighting a novel mechanism contributing to global lipid perturbations in heart failure.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/acylcarnitines-in-human-heart-failure/.


The effect of progesterone supplementation post mating and shearing of ewes in early pregnancy on the reproductive performance of ewes and birthweight of lambs.
To determine whether short-term progesterone supplementation post mating or shearing of ewes in early pregnancy affected either the proportion of ewes that lambed or that had multiple lambs, or the birthweight of lambs. Romney ewes (n=457) were synchronised in oestrus using controlled internal drug-releasing (CIDR) devices containing progesterone, and mated to Romney rams over a 5-day period. The mid-point of mating (Day 0) occurred 2 days after the withdrawal of CIDR devices. Ewes mated (n=397) were randomly allocated to one of four treatment groups: shearing at Day 5, shearing at Day 30, no shearing, and no shearing plus progesterone supplementation using a CIDR device inserted on Day 3 for 6 days. During the period from Day 5 to Day 27, six harnessed Suffolk rams were placed with the ewes and matings recorded. At Day 48, all ewes that did not return to the Suffolk rams were scanned for pregnancy using ultrasound. At Day 140, single- and multiple-bearing ewes were set-stocked at 15.1 and 12.2 ewes/ha, respectively, and equivalent numbers of ewes from each treatment group were placed in each paddock. Blood samples from 10 unshorn and 10 progesterone-supplemented ewes were collected on Days 3, 6 and 9, and analysed for plasma progesterone concentrations. Lambs were identified to their dam and weighed within 12 h of birth, and again at 27 and 93 days after the mid-point of lambing. The ewes were weighed at regular intervals throughout the trial. Plasma progesterone concentrations of supplemented ewes were higher than those of unsupplemented ewes (3.28 vs 1.75 ng/ml) on Day 6 (p=0.02) but not on Day 9 (4.58 vs 4.63 ng/ml). Treatment of ewes had no effect on either the proportion of ewes which lambed to the synchronised mating period or that had multiple lambs. Lambs born to ewes shorn at Day 30 tended (p=0.09) to be heavier at birth (by 0.28 kg) than those born to unshorn ewes but this effect was not evident when data were corrected for length of gestation. Neither shearing at Day 5 nor progesterone supplementation had any effect on the birthweight of lambs, and the treatment of ewes had no effect on the survival rate of lambs to weaning. Progesterone supplementation for 6 days beginning 3 days post mating did not increase either the proportion of ewes that lambed or that had multiple lambs, or the birthweight of lambs. Shearing 5 days after mating had no significant effect on the reproductive performance of ewes and need not be avoided, but is unlikely to result in an increase in lamb birthweight. Shearing ewes at Day 30 may result in an increase in the birthweight of lambs but, ideally, ewes should be further advanced in pregnancy before shearing is undertaken.


Self-Healable and Stretchable Ionic-Liquid-Based Thermoelectric Composites with High Ionic Seebeck Coefficient.
The advancement of wearable electronics, particularly self-powered wearable electronic devices, necessitates the development of efficient energy conversion technologies with flexible mechanical properties. Recently, ionic thermoelectric (TE) materials have attracted great attention because of their enormous thermopower, which can operate capacitors or supercapacitors by harvesting low-grade heat. This study presents self-healable, stretchable, and flexible ionic TE composites comprising an ionic liquid (IL), 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMIM:OTf); a polymer matrix, poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP); and a fluoro-surfactant (FS). The self-healability of the IL-based composites originates from dynamic ion-dipole interactions between the IL, the PVDF-HFP, and the FS. The composites demonstrate excellent ionic TE properties with an ionic Seebeck coefficient (Si ) of ≈38.3 mV K-1 and an ionic figure of merit of ZTi = 2.34 at 90% relative humidity, which are higher than the values reported for other IL-based TE materials. The IL-based ionic TE composites developed in this study can maintain excellent ionic TE properties under harsh conditions, including severe strain (75%) and multiple cutting-healing cycles.


Unique responses of midbrain CART neurons in macaques to ovarian steroids.
CART (cocaine and amphetamine regulated transcript) is a neuropeptide involved in the control of several physiological processes, such as response to psychostimulants, food intake, depressive diseases and neuroprotection. It is robustly expressed in the brain, mainly in regions that control emotional and stress responses and it is regulated by estrogen in the hypothalamus. There is a distinct population of CART neurons located in the vicinity of the Edinger-Westphal nucleus of the midbrain that also colocalize urocortin-1. The aims of this study were 1) to determine the distribution of CART immunoreactive neurons in the monkey midbrain, 2) to examine the effects of estrogen (E) and progesterone (P) on midbrain CART mRNA and peptide expression and 3) to determine whether midbrain CART neurons contain steroid receptors. Adult female rhesus monkeys (Macaca mulatta) were spayed and either treated with placebo (OVX), estrogen alone (E), progesterone alone (P) or E+P. Animals were prepared (a) for RNA extraction followed by microarray analysis and quantitative (q) RT-PCR (n=3/group); (b) for immunohistochemical analysis of CART and CART+tryptophan hydroxylase (TPH), CART+estrogen receptors (ER) or CART+progesterone receptors (n=5/group) and (c) for Western blots (n=3/group). Both E- and E+P-administration decreased CART gene expression on the microarray and with qRT-PCR. Stereological analysis of CART immunostaining at five levels of the Edinger-Westphal nucleus indicated little effect of E or E+P administration on the area of CART immunostaining. However, P administration increased CART-immunopositive area in comparison to the OVX control group with Student's t-test, but not with ANOVA. CART 55-102 detection on Western blot was unchanged by hormone administration. ERbeta and PR were detected in CART neurons and CART fibers appeared to innervate TPH-positive serotonin neurons in the dorsal raphe. In summary, E decreased CART mRNA, but this effect did not translate to the protein level. Moreover, P administration alone had a variable effect on CART mRNA, but it caused an increase in CART immunostaining. Together, the data suggest that CART neurons in the midbrain have a unique steroid response, which may be mediated by nuclear receptors, neuroactive steroids or interneurons.


Gender differences in emotion perception and self-reported emotional intelligence: A test of the emotion sensitivity hypothesis.
Previous meta-analyses and reviews on gender differences in emotion recognition have shown a small to moderate female advantage. However, inconsistent evidence from recent studies has raised questions regarding the implications of different methodologies, stimuli, and samples. In the present research based on a community sample of more than 5000 participants, we tested the emotional sensitivity hypothesis, stating that women are more sensitive to perceive subtle, i.e. low intense or ambiguous, emotion cues. In addition, we included a self-report emotional intelligence test in order to examine any discrepancy between self-perceptions and actual performance for both men and women. We used a wide range of stimuli and models, displaying six different emotions at two different intensity levels. In order to better tap sensitivity for subtle emotion cues, we did not use a forced choice format, but rather intensity measures of different emotions. We found no support for the emotional sensitivity account, as both genders rated the target emotions as similarly intense at both levels of stimulus intensity. Men, however, more strongly perceived non-target emotions to be present than women. In addition, we also found that the lower scores of men in self-reported EI was not related to their actual perception of target emotions, but it was to the perception of non-target emotions.


Saudi Society for Cardiac Surgeons consensus document on COVID-19, April 1, 2020.
The COVID-19 pandemic represents an international health crisis that is challenging to all governments. Health practitioners in different fields have a duty to guide people and governments to achieve safe health practices. The Saudi Society for Cardiac Surgeons recognizes that it is difficult to establish evidence-based guidelines for safe cardiac surgery practices in such a crisis because this is an unprecedented health pandemic. So we decided to work with our colleagues in other societies by reviewing different recommendations and safe practices issued by different health organizations and scientific societies. The aim was to come up with recommendations that could guide hospitals, physicians, and other members of the healthcare team on the best available practices that are applicable to our community and that will not only ensure optimum patient care delivery but also protect healthcare workers from the risk of infection and aid the national effort in containing and managing this worldwide pandemic.


A systematic review regarding women's emotional and psychological experiences of high-risk pregnancies.
High-risk pregnancy refers to a pregnancy that negatively affects the health of the mother, the baby, or both. High-risk pregnancy evokes a range of emotional and psychological experiences for the expectant mother, and can adversely affect both the mother and the baby's health. Medical research on high-risk pregnancy abounds, while women's emotional/psychological experiences are not sufficiently documented, and hence much less attention and/or programming is directed to support women with high risk pregnancies. The aim of this review is to present published evidence of how studies reported on the emotional and psychological experiences of a woman's high-risk pregnancy journey. The systematic review examined qualitative studies over a 10 year period that were published between January 2006 and June 2017. These studies were identified on 10 databases. The study utilised three stages of review (i.e. abstract reading, title reading, and full-text reading) and for a successful conduction of the meta-synthesis, this study applied one of the phases provided by Noblit and Hare. The findings provide empirical evidence that women's emotional and psychological experiences (i.e. shock, fear, frustration, grief, isolation and loneliness, anger, sadness, guilt, and mental health disorder) are evident throughout their high-risk pregnancies experience.


Relationship between radiographic hilar lymphadenopathy and serologic titers for Coccidioides sp. in dogs in an endemic region.
Hilar lymphadenopathy is a common radiographic finding in coccidioides infections. Serologic studies are used most often for the diagnosis of coccidioidomycosis in endemic areas, with IgG titers > 1:8 considered positive for infection and lower IgG titers of < 1:8 considered indicative of exposure and not necessarily related to organism presence. The objective of this study was to determine the relationship of hilar lymphadenopathy to coccidioidomycosis titers for dogs in an endemic area. A positive association between these parameters would allow treatment to be initiated before obtaining titer results. Thoracic radiographs of 131 dogs from an endemic area were reviewed for evidence of hilar lymphadenopathy. These results were compared with serology results. There was a significant association between hilar lymphadenopathy and a positive serology result (P < 0.001). With hilar lymphadenopathy as a predictor of a positive titer result, sensitivity was 28.0%, specificity was 91.5%, the positive predictive value was 43.8%; and the negative predictive value was 84.4%. There was no association between the titer result and gender, age, or weight. The radiographic finding of hilar lymphadenopathy appears to be a useful indicator of coccidioidomycosis infection in an endemic population of dogs supporting the treatment of patients for coccidioidomycosis when hilar lymphadenopathy is present and before obtaining serology results.


Perfusion improves tissue architecture of engineered cardiac muscle.
Cardiac muscle with a certain threshold thickness, uniformity of tissue architecture, and functionality would expand the therapeutic options currently available to patients with congenital or acquired cardiac defects. Cardiac constructs cultured in well-mixed medium had an approximately 100-microm-thick peripheral tissue-like region around a relatively cell-free interior, a structure consistent with the presence of concentration gradients within the tissue. We hypothesized that direct perfusion of cultured constructs can reduce diffusional distances for mass transport, improve control of oxygen, pH, nutrients and metabolites in the cell microenvironment, and thereby increase the thickness and spatial uniformity of engineered cardiac muscle. To test this hypothesis, constructs (9.5-mm-diameter, 2-mm-thick discs) based on neonatal rat cardiac myocytes and fibrous polyglycolic acid scaffolds were cultured either directly perfused with medium or in control spinner flasks. Perfusion improved the spatial uniformity of cell distribution and enhanced the expression of cardiac-specific markers, presumably due to the improved control of local microenvironmental conditions within the forming tissue. Medium perfusion could thus be utilized to better mimic the transport conditions within native cardiac muscle and enable in vitro engineering of cardiac constructs with clinically useful thicknesses.


Identification of amastigote-specific antigens of Leishmania donovani using kala-azar patient sera.
Antigenic characterization of the soluble fraction of axenic amastigotes of Leishmania donovani ( strain Dd8, causative agent of Indian kala-azar) and their comparison with promastigotes is reported. The axenic amastigotes were assessed for their immunological status employing anti-A2 monoclonal antibody which is extremely specific for L. donovani amastigotes. SDS-PAGE of 35[S] methionine labeled proteins of the two parasite stages exhibited few stage specific and some conserved antigens in both the stages. An increased synthesis of heat shock proteins was observed in axenic amastigotes. Western blot experiments employing sera of kala azar positive patients identified immunodominent antigens of 116,83,26 and 12 kDa in axenic amastigotes which were not present in promastigotes. These amastigote stage specific antigens may have immense potential in immunodiagnosis and prophylaxis of kala-azar.


Carbon nanotube disposable detectors in microchip capillary electrophoresis for water-soluble vitamin determination: analytical possibilities in pharmaceutical quality control.
In this work, the synergy of one mature example from "lab-on-chip" domain, such as CE microchips with emerging miniaturized carbon nanotube detectors in analytical science, is presented. Two different carbon electrodes (glassy carbon electrode (GCE) 3 mm diameter, and screen-printed electrode (SPE) 0.3 mm x 2.5 mm) were modified with multiwalled carbon nanotubes (MWCNTs) and their electrochemical behavior was evaluated as detectors in CE microchip using water-soluble vitamins (pyridoxine, ascorbic acid, and folic acid) in pharmaceutical preparations as representative examples. The SPE modified with MWCNT was the best electrode for the vitamin analysis in terms of analytical performance. In addition, accurate determination of the three vitamins in four different pharmaceuticals was obtained (systematic error less than 9%) in only 400 s using a protocol that combined the sample analysis and the methodological calibration.


Does maternal obesity impact pregnancy-related deaths? Michigan experience.
Obesity is a multifactorial non-communicable condition that has become a public health epidemic worldwide. The Fifth Millennium Development Goal established the goal of a 75% reduction in the maternal mortality ratio (MMR) between 1990 and 2015. Maternal mortality has been difficult to track over time. Obesity affects pregnancy in more than 50% of women of reproductive age in the state of Michigan; the potential impact of maternal obesity and pregnancy-related deaths (PRDs) has not been studied in Michigan. We conducted a secondary analysis of maternal death cases originally reviewed by the Michigan Maternal Mortality Review Committee from 2004 to 2006 seeking to evaluate the impact of maternal obesity on PRD. Two hundred and five maternal deaths occurred during the period of the study, 61 were classified as PRD. The observed occurrence of PRDs in the obese population was 36 cases while in the non-obese was 25 cases. The study showed a 3.7× risk of PRD in the obese parturient.


Post-vaccination Monitoring to Assess Foot-and-Mouth Disease Immunity at Population Level in Korea.
In South Korea, domestic cattle, pigs, and goats were subjected to mandatory foot-and-mouth disease (FMD) vaccination and year-round serosurveillance since 2011. In 2020, approximately USD 95 million was spent solely for FMD vaccine purchase for 59 million livestock, and 1.25 million samples were tested to estimate the population immunity and demonstrate the absence of virus circulation. As the FMD vaccination program was revised in 2018, the post-vaccination monitoring (PVM) was designed to evaluate the effectiveness of the vaccine program of three vaccines approved for routine use. To this end, monitoring post-vaccination immunity has been conducted by collecting 35,626 serum samples at 28 days post-vaccination following regular national vaccinations, which were carried out in April and in October in 2020. The design of the serological test for PVM was specially targeted at particular livestock groups, including dairy cattle, goats, and beef cattle aged 6-12 months, which were generally estimated to have a low expected seroprevalence. The risk factors had also been identified, considering the increased likelihood of infection in a particular location, herd size, and husbandry system applied in a targeted sample collection. Serum sample collection and SP-O and NSP antibody tests were performed by local veterinary laboratories using commercially available ELISAs. The current FMD vaccination program, which was performed twice a year following the regimen of primary vaccination and boost, resulted in over 80% population immunity. The seroprevalence monitored after the vaccination in fall was higher than the one studied in spring except in pigs. It was demonstrated that the seroprevalence of risk-based targeted samples ranged from 93.8 to 100% in cattle, 63.2 to 100% in pigs, and 20.0 to 100% in goats. Of note is the area near the North Korean borders which showed a relatively low seroprevalence among the targeted regions, and no NSP sero-positive reactor was detected in this region. When subpopulation immunity at the individual level was assessed, the seroprevalence in young cattle stock was slightly lower (95.8%) than that of adults (98.4%). In conclusion, the FMD vaccination campaign has been successfully implemented in Korea, and the PVM can be a supplementary program for massive routine surveillance in terms of providing timely information needed both to estimate population immunity and to properly target "risk-based surveillance."


Lack of complement activation by human IgA immune complexes.
Complement activation may play an important role in renal injury associated with glomerular deposition of IgA immune complexes. The ability of naturally occurring human IgA immune complexes (IgA-IC) and covalently cross-linked human IgA oligomers (X-IgA) to activate complement were examined in vitro and in vivo. Large-sized IgA-IC were isolated from a patient's serum by affinity purification (Jacalin-Sepharose) and gel chromatography. Stable X-IgA were prepared by chemical cross-linking with a heterobifunctional reagent, N-succinimdyl 3-(2-pyridyl-dithio) propionate (SPDP). Treatment of fresh normal human serum with large amounts of either IgA-IC or X-IgA failed to activate C3. The C3 consumption was measured immunochemically by the decrease of the B antigen on the native C3 and by the generation of iC3b. Addition of these complexes to serum did not result in cleavage of factor B. Administration of human IgA-IC or X-IgA to mice, killed after 6 h, resulted in glomerular deposition of IgA. Despite the presence of intense glomerular IgA deposits no C3 was detected. Collectively, these findings suggest that neither soluble nor renal localized human IgA complexes activate complement.


Cytotoxic trans-oriented platinum complexes only form adducts with single-stranded oligodeoxynucleotides.
The reactions of the anticancer complex trans-[PtCl(2)[(E)-HN==C(OMe)Me](2)] (trans-EE) with both single-stranded and double-stranded deoxyribonucleotides have been studied by HPLC and 2D [(1)H,(15)N] HMQC NMR spectroscopy and compared with those of cis-[PtCl(2)(NH(3))(2)] (cis-DDP). Reactions of trans-EE with the single-stranded oligonucleotides d(CCTCGCTCTC) and d(CCTGGTCC) proceed rapidly through solvolysis of the starting substrate and subsequent formation of G-N7/monochloro trans-EE adducts. The rate of reaction is comparable to that of formation of an adduct from trans-EE and the dinuclotide d(ApG). Quite unexpectedly, the double-helical duplexes, d(TATGGTACCATA)(2) and d(TATGGCCATA)(2), with no terminal G residues, are practically inert towards trans-EE, and only minor species (< 5 % as estimated from HPLC traces) appear during 24 h reaction time. However, the duplexes d[(CCTCGCTCTC). (GAGAGCGAGG)] and d(GATAGGCCTATC)(2), which contain both terminal and central G residues, undergo platination only at the terminal, solvent-exposed, G residues, thereby confirming that the interior of the duplex is not accessible to trans-EE due to steric hindrance. In contrast, cis-DDP was found to bind exclusively to the central GG pair in d(GATAGGCCTATC)(2).


Surgical Delay Facilitates Pedicled Nipple-sparing Mastectomy and Reconstruction in the Ptotic Patient.
Significant ptosis is a relative contraindication for nipple-sparing mastectomy and reconstruction. Repositioning of the nipple on the reconstructed breast is best accomplished using a pedicled approach that is risky in the immediate setting. We utilized a surgical delay before reconstruction that allowed for repositioning of the nipple-areola complex on an inferior pedicle. This also allows for resizing of the nipple-areola complex, reliable complete coverage of the prosthesis with viable tissue, and creation of an ideal skin envelope in patients with skin excess. Here, we present the first description of a surgical delay to facilitate pedicled nipple-sparing mastectomy and reconstruction.


Influence of Nutrient (NPK) Factors on Growth, and Pharmacodynamic Component Biosynthesis of Atractylodes chinensis: An Insight on Acetyl-CoA Carboxylase (ACC), 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGR), and Farnesyl Pyrophosphate Synthase (FPPS) Signaling Responses.
In the planting of crops, especially medicinal plants, formula fertilization is important for improving the utilization rate of elements, soil quality, crop yield, and quality. Therefore, it is important to study targeted fertilizer application schemes for sustainable agricultural development and environmental protection. In this study, an L9(34) orthogonal design was used to conduct a field experiment to study the effects of NPK combined application on the growth and pharmacodynamic component biosynthesis of Atractylodes chinensis (DC.) Koidz. Results showed that after applying a base fertilizer at the seedling stage (late May), topdressing at the vegetative stage (late June) and fruit stage (late August) was beneficial to the growth and development of A. chinensis. The high concentrations of phosphorus were conducive to the accumulation of yield and effective components, and the best harvest time was after late October. Principal component analysis (PCA) showed that the comprehensive score of T6 treatment was the highest, indicating that the optimal fertilization scheme for the high yield and high quality of A. chinensis was (N2P3K1): N 180, P2O5 225, and K2O 105 kg⋅ha-1. A signaling response analysis showed that during the growth and development of A. chinensis, the T6 fertilization scheme had clear effects on the activity and gene expression of the key enzymes acetyl-CoA carboxylase (ACC) and farnesyl pyrophosphate synthase (FPPS). Under the T4 [(N2P1K2): N 180, P2O5 75, and K2O 210 kg⋅ha-1] fertilization scheme, the activity and gene expression of the key enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) were higher. Moreover, ACC was closely related to the synthesis of the polyacetylene component atractylodin, and FPPS played an important regulatory role in the synthesis of sesquiterpene components atractylenolide II, β-eudesmol, and atractylon. In summary, the high phosphorus fertilization scheme T6 could notably increase the yield of A. chinensis, and promote the accumulation of polyacetylene and sesquiterpene volatile oils by increasing the expression of ACC and FPPS. Therefore, we postulate that the precise application of nutrients (NPK) plays a vital role in the yield formation and quality regulation of A. chinensis.


Increased incorporation of 5-fluorodeoxyuridine into DNA of human T-lymphoblastic cell lines.
Various human leukemoblastoid cell lines in logarithmic growth were incubated for 16 hr with 0.5 microM [3H]fluorodeoxyuridine (FdUrd) and the incorporation of [3H]FdUrd into DNA was measured. T-acute lymphoblastic leukemia (T-ALL) cell lines incorporated 2.4-7.0 times more [3H]FdUrd into newly synthesized DNA than cell lines from B-lymphoid, pre B-ALL, null cell ALL and acute myeloid leukemia cells. T-ALL cells incorporated 1.93-3.15 pmol of [3H]FdUrd nucleotides into DNA per 10(7) cells. The amount of [3H]FdUrd incorporated into DNA was inversely correlated with the activity level of uracil DNA glycosylase of the cells. On the other hand, no correlation was observed between the incorporation and the level of deoxyuridine triphosphate diphosphohydrolase of each cell line. However, the amount of FdUrd incorporated into DNA could not be correlated with the antiproliferative activity of FdUrd against these cell lines.


Increased chronic disease prevalence among the younger generation: Findings from a population-based data linkage study to inform chronic disease ascertainment among reproductive-aged Australian women.
Chronic disease represents an ongoing public health challenge in Australia with women disproportionately affected and at younger ages compared to men. Accurate prevalence and ascertainment of chronic disease among women of reproductive age at the population level is essential for meeting the family planning and reproductive health challenges that chronic diseases pose. This study estimated the prevalence of chronic disease among younger Australian women of reproductive age, in order to ascertain key conditions that would benefit from targeted family planning support strategies. Population-level survey data from the 1973-78 and 1989-95 cohorts of the Australian Longitudinal Study on Women's Health were linked to health service use, pharmaceutical, cancer and cause of death data to ascertain the prevalence and chronic disease trends for ten chronic health conditions associated with poor maternal and foetal outcomes. Individual chronic disease algorithms were developed for each chronic disease of interest using the available linked datasets. Lifetime prevalence of chronic disease varied substantially based on each individual data source for each of the conditions of interest. When all data sources were considered, all conditions with the exception of mental health conditions were higher among women in the 1973-78 cohort. However, when focused on point prevalence at similar ages (approximately 25-30 years), the chronic disease trend for women in the 1989-95 cohort was substantially higher, particularly for mental health conditions (70.4% vs 23.6%), diabetes (4.5% vs 1.3%) and multimorbidity (17.9% vs 9.1%). Given the low concordance between individual data sources, the use of multiple data sources are recommended for chronic disease research focused on women of reproductive age. In order to reduce the increasing chronic disease and multimorbidity trend among women, strategic chronic disease interventions are required to be implemented in childhood and adolescence to ensure the long-term health of not only current but also future generations.


Integral proteins of the extracellular matrix fibrils of Myxococcus xanthus.
The extracellular matrix fibrils of Myxococcus xanthus are mediators of cell-cell cohesion and as such are required for the maintenance of the social lifestyle characteristic of these prokaryotes. The fibrils have also been implicated as factors involved in contact-mediated cell interactions and in signal exchange. The fibrils are extracellular carbohydrate structures with associated proteins. All of the major proteins associated with the fibrils react with monoclonal antibody 2105 and can be removed from the fibrils only by boiling with sodium dodecyl sulfate (SDS) and beta-mercaptoethanol. For consistency with their integral association with the fibrils, we have designated this class of proteins as integral fibrillar proteins class 1 (IFP-1). IFP-1 comprises five major proteins whose molecular sizes range from 66 to 14 kDa. All of the proteins in IFP-1 have been purified from isolated fibrils by electroelution after size separation on SDS-PAGE gels. Analysis of the purified proteins suggested that the forms with different molecular sizes result from the aggregation of a single small-molecular-size subunit. Fingerprint analysis and amino acid composition profiles confirmed the identity among the different members of IFP-1. The sequence of the 31 amino-terminal amino acids of the 31-kDa form of IFP-1 (IFP-1:31) was determined. There was no significant homology to other known protein sequences. During development there is a dramatic shift in the banding pattern of IFP-1 proteins without any apparent overall loss of total protein.


[Orthodontic treatment in multidisciplinary sequential treatment of patients with cleft lip and palate].
Cleft lip and palate is the most common congenital maxillofacial defect. The modern treatment of cleft lip and palate is a sequential treatment with multidisciplinary collaboration, which can restore the maxillofacial morphology and function, and rebuild the psychosocial adaptation of the patients. Orthodontic treatment is almost throughout whole process of the sequential treatment. Due to the professional attention to maxillofacial growth and development, orthodontists have become one of the most crucial members during the multidisciplinary treatment of cleft lip and palate. Orthodontists are required in the different stages of maxillofacial growth and development to provide suggestions and necessary treatment. By orthodontic treatment, it can not only solve the problem of malocclusion and promote the maxillofacial growth and development, but also create a favourable condition for other therapies of sequential treatment, such as cleft lip and palate repair, bone grafting, prosthodontics, and even mental health. In order to improve the therapeutic effect of comprehensive treatment and to alleviate the burden of patients, orthodontists should learn more about the treatment of cleft lip and palate. This article mainly introduced the craniofacial deformities of cleft lip and palate and the progress of orthodontic treatment in the multidisciplinary treatment of cleft patients.


A high glycolytic flux supports the proliferative potential of murine embryonic stem cells.
Embryonic stem (ES) cells are immortal and present the ability to self-renew while retaining their ability to differentiate. In contrast, most primary cells possess a limited proliferative potential, and when this is exhausted, undergo an irreversible growth arrest termed senescence. In primary cells, senescence can be also triggered by a variety of stress to which ES cells are highly refractory. Here the authors report that the proliferative capacity of murine ES cells closely correlates with high activity of different glycolytic enzymes, elevated glycolytic flux, and low mitochondrial oxygen consumption. The direct relation between glycolytic flux and the ability of ES cells to proliferate is further remarked in experiments where glycolysis or ES cell self-renewal was specifically inhibited. It was previously reported that the upregulation of glycolysis in primary cells results in life span extension. The authors hypothesize that the naturally high glycolytic flux observed in murine ES cells can be responsible for their unlimited proliferative potential.


Grueneberg ganglion neurons are activated by a defined set of odorants.
Based on a variety of recent findings, the Grueneberg ganglion (GG) in the vestibule of the nasal cavity is considered as an olfactory compartment. However, defined chemical substances that activate GG neurons have not been identified. In this study, the responsiveness of murine GG cells to odorants was examined by monitoring the expression of the activity-dependent gene c-Fos. Testing a number of odorous compounds, cells in the GG were found to respond to dimethylpyrazine (DMP) and a few related substances. These responses were dose-dependent and restricted to early postnatal stages. The DMP-responsive GG cells belonged to the subset of GG neurons that coexpress the signaling elements V2r83, GC-G, and CNGA3. These cells have been previously reported to respond to cool ambient temperatures as well. In fact, cool temperatures enhanced DMP-evoked responses of GG cells. These findings support the concept that the GG of neonatal mice operates as a dual sensory organ that is stimulated by both the odorous compound DMP and cool ambient temperatures.


Toxicological and clinical aspects of cyanide metabolism.
This contribution deals with the occurrence of cyanide and its biological pathways in the body. Especially possibilities of detoxification are pointed out. Intoxications are caused by acute and chronical cyanide uptake. Tobacco amblyopia, retrobulbar neuritis in pernicious anaemia, Leber's optic atrophy, Nigerian nutritional neuropathy, and sterility in female heavy smokers are attributed to cyanide intoxication. Various methods for treating acute and chronic cyanide intoxication are discussed.


Escherichia coli cyclopropane fatty acid synthase: is a bound bicarbonate ion the active-site base?
Cyclopropane synthases catalyze the cyclopropanation of unsaturated fatty acid using S-adenosyl-L-methionine as the methylene donor. The crystal structure of three cyclopropane synthases from Mycobacterium tuberculosis showed a bicarbonate ion bound in the active site that was proposed to act as a general base in the reaction mechanism [Huang, C., Smith, V., Glickman, M. S., Jacobs, W. R., and Sacchettini, J. C. (2002) J. Biol. Chem. 277, 11559-11569]. Because the in vitro activity of M. tuberculosis cyclopropane synthases has not yet been reported and because the ligands of the bicarbonate ion are all strictly conserved in cyclopropane synthases, we used the closely related Escherichia coli cyclopropane fatty acid synthase for this study. The putative ligands that share a hydrogen bond with the bicarbonate through their side chains were mutated. H266A, Y317F, E239A, and E239Q mutants were thus constructed and purified, and their catalytic efficiencies were 5.3, 0.7, 0.2, and <0.02%, respectively. C139 that is bound to the bicarbonate by its NH amide had already been mutated to serine in a previous work, and this mutant retains 31% of the activity of the wild-type enzyme. Kinetic analyses and binding studies using spectrofluorimetry showed that these mutations affected the catalytic constant rather than the binding of the substrates. While addition of free bicarbonate had almost no effect on the wild-type enzyme activity, all mutants, with the exception of E239A and E239Q, were rescued by the addition of free bicarbonate. The catalytic efficiencies of the rescued mutants were 85, 16, and 14% for C139S, H266A, and Y317F, respectively. This effect was specific to bicarbonate. The kinetic parameters of the rescued mutants were determined, and it is shown that the rescuing effect is due to an increase in kcat. These data are interpreted by assuming that the E. coli cyclopropane fatty acid synthase specifically binds a bicarbonate ion that is involved in catalysis, as proposed for the M. tuberculosis enzymes, and that mutation of the bicarbonate ligands decreases the affinity for that ion. However, because the E239Q mutation could not be rescued, we propose that E239 forms a catalytic dyad with the bicarbonate to perform the proton abstraction necessary in the chemical pathway to the cyclopropane ring.


The detection and importance of outliers in the in vivo micronucleus assay.
Micronucleus tests are generally analysed statistically for differences between the means of treated and control groups. 'Outliers' may either be rejected or grouped together with data from less responsive animals. In either case, a valuable indicator of a small, more sensitive (responder) population sub-group may then be missed. To alleviate this problem, we have developed an additional strategy, based on historic data, for the detection of any single animal with a significant increase in micronucleated polychromatic erythrocytes in an otherwise insignificant treatment group. Forty-one sets of negative control data (of five male and five female CD-1 mice each) have been analysed. Within each set there were no significant male to female differences and data were consistent with a Poisson distribution. Pooled data from all 41 sets showed slightly hyper-Poisson variation and were adequately described by the negative binomial distribution. The negative binomial probability generating function was used to show that six or more micronuclei per 1000 polychromatic cells from one treated animal would be significant for our laboratory, methodology and strain of mouse, provided that concurrent negative control data conformed with historic values. Changes in methodology desirable for this type of analysis include increasing the number of mice in each test group and possible compensation by a reduction in the number of test groups.


Study Protocol: Transition_psy a Multicenter Prospective Longitudinal Cohort Study Assessing Risk and Protective Factors to Develop Psychopathology in Transitional Age Youth in Belgium.
Introduction: Emerging adults are a particularly at-risk population in mental health. The primary aim of the Transition_psy study is to evaluate changes in mental health care need and quality of life during transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS). The relationship between these changes and genetic or environmental vulnerabilities and clinical dimensions representing risk and protective factors to the development of psychopathology will be analyzed. We also aim to explore how each factor plays, specifically, a role in developing internalizing and externalizing symptoms, in order to predict the most common paths of psychopathology in transitional age youth (TAY). Methods and Analysis: Transition_psy is a multicenter prospective longitudinal cohort study. The transversal and trans-diagnostic approach consists of a dimensional evaluation: 300 youth at the age of 17 will be included in a cohort of in-patients, out-patients and control group. Participants will be assessed at baseline (T0) and 24 months later (T1). The primary objective to determine changes in self-rated Health Of The Nation Outcome Scales For Children And Adolescents (HONOSCA-SR) and WHO Quality of Life-BREF (WHOQOL-BREF) scores between T0 and T1. Pearson correlation and mediation analysis will be performed. A secondary objective analysis using mediation and moderation models with several dimensional aspects, including self-reported and cognitive measures, will be conducted to disentangle the potential relationships between the two scores. Discussion: Transition from CAMHS to AMHS occurs at a crucial age in terms of the continuum between adolescent and adulthood psychopathology. This collaborative and cohesive protocol between CAMHS and AMHS represents the first national cohort study about Transition Psychiatry in French-speaking Belgium. Ethics and Dissemination: The study protocol was approved by the Institutional Review Boards (IRB) of the three participating sites. Results will be published in peer-reviewed journals and disseminated at national and international conferences. This trial was registered in ClinicalTrials.gov (Identifier: NCT04333797) on 3 April 2020.


Molecular Breeding for Ascochyta Blight Resistance in Lentil: Current Progress and Future Directions.
Lentil (Lens culinaris Medik.) is a diploid (2n = 2x = 14), self-pollinating, cool-season, grain legume that is cultivated worldwide and is highly valuable due to its high protein content. However, lentil production is constrained by many factors including biotic stresses, majority of which are fungal diseases such as ascochyta blight (AB), fusarium wilt, rust, stemphylium blight, anthracnose, and botrytis gray mold. Among various diseases, AB is a major -problem in many lentil-producing countries and can significantly reduce crop production. Breeding for AB resistance has been a priority for breeding programs across the globe and consequently, a number of resistance sources have been identified and extensively exploited. In order to increase the efficiency of combining genes from different genetic backgrounds, molecular genetic tools can be integrated with conventional breeding methods. A range of genetic linkage maps have been generated based on DNA-based markers, and quantitative trait loci (QTLs) for AB resistance have been identified. Molecular markers linked to these QTLs may potentially be used for efficient pyramiding of the AB disease resistance genes. Significant genomic resources have been established to identify and characterize resistance genes, including an integrated genetic map, expressed sequence tag libraries, gene based markers, and draft genome sequences. These resources are already being utilized for lentil crop improvement, to more effectively select for disease resistance, as a case study of the Australian breeding program will show. The combination of genomic resources, effective molecular genetic tools and high resolution phenotyping tools will improve the efficiency of selection for ascochyta blight resistance and accelerate varietal development of global lentil breeding programs.


Retention and caries-preventive effect of glass ionomer and resin-based sealants: An 18-month-randomized clinical trial.
The objective of this study was to compare the retention and caries-preventive effect of glass ionomer (Fuji Triage) and resin-based (Clinpro) sealants among 6-9-year-old children. This split-mouth, randomized clinical trial covered 35 children/140 fully erupted permanent first molars. Evaluation was conducted by two independent examiners after 6, 12, and 18 months and the data were compared in relation to the children's caries risk and age groups. The Kaplan-Meier survival method and chi-square test were used for analysis. There were no statistically significant differences in the survival of partial and fully retained sealants or in the survival of caries-free pits and fissures between glass-ionomer and resin-based sealants. In terms of retention, both sealants performed better in the younger age group at the end of the study, and showed better caries prevention in moderate caries risk children. After 18 months, both sealants had comparable retention and caries-preventive effects in 6-9-year old children.


Limb girdle muscular dystrophy: a pathological and immunohistochemical reevaluation.
Ninety-seven muscle biopsies from 81 limb girdle muscular dystrophy (LGMD) patients [32 autosomal recessive (AR), 15 autosomal dominant (AD), 34 sporadic] were morphologically reevaluated. Sarcoglycan analysis was done in 37 available muscle biopsies of AR and sporadic patients. Chi-square tests were used to analyze the relation between abnormalities in AR/sporadic versus AD cases. Eighty percent of the muscle biopsies showed a predominantly dystrophic pattern, 20% showed myopathic changes, and 17% of these also had neurogenic changes. Muscle histology was not significantly different between AR/sporadic and AD LGMD; however, the observed abnormalities were more pronounced in the AR/sporadic group. Collections of inflammatory cells were observed in 25% and 10% of the AR/sporadic and AD group, respectively. Sarcoglycanopathy was diagnosed in 25% of the AR and sporadic patients of the 37 families tested. We conclude that the histological picture of AR/sporadic and AD LGMD is essentially the same, and sarcoglycanopathy constitutes an important part of the AR/sporadic patients.


Cardiac beta 2-adrenoceptors and the inotropic response to exercise in man.
To find out what role, if any, beta 2-adrenoceptors play in cardiac contractility, the heart rate, stroke volume and cardiac output of twelve healthy male and female volunteers (aged 18-28 years) were studied at rest (standing) and during two stages of treadmill exercise, 2 h after ingestion of propranolol (100 mg) or atenolol (100 mg) or a placebo, on different occasions, in a double-blind crossover manner. Cardiac output was measured by a carbon dioxide-rebreathing method. Atenolol and propranolol caused equal reductions in heart rate at rest, and in heart rate and cardiac output during exercise (p less than 0.001, two-way analysis of variance). Neither atenolol nor propranolol had any significant effect on resting cardiac output, resting stroke volume or stroke volume during exercise. Since atenolol (100 mg) has been shown to be beta 1-adrenoceptor-selective, we conclude that cardiac inotropic function during exercise is largely beta 1-adrenoceptor-mediated with little or no beta 2-adrenoceptor involvement.


Helices and other secondary structures of beta- and gamma-peptides.
The principal secondary structural motifs adopted by peptides assembled from beta-amino acid units are discussed: the 14-, 12-, 10-, 12/10-, and 8-helices, as well as the hairpin turn, extended structures, stacks, and sheets. Features that promote a particular folding propensity are outlined and illustrated by structures determined in solution (NMR) and in the solid-state (x-ray). The N-C(beta)-C(alpha)-CO dihedral angles from molecular dynamics simulations, which are indicative of a particular secondary structure, are presented. A brief description of a helix and a turn of gamma-peptides is also given.


Work-related bystander deaths in New Zealand: a significant hidden problem.
To estimate the extent of bystander work-related traffic fatal injury for New Zealand as well as the contribution of all bystander events to the total burden of work-related fatal traffic injury and work-related fatal injury in general. Potential cases were identified from national administrative databases. The circumstances of the deaths in each incident were reviewed directly from coronial files to determine work-relatedness. For 1985-1998 we identified 1447 people whose death was associated with another person's work activity on a public road and who were not working at the time. This compares with 241 "working" and 192 "commuting" deaths on a public road for the same period. Bystanders thus represented approximately 75% of the work-related fatal traffic crash injury problem. We estimate that (on average) approximately 115 bystanders were killed each year and this represents approximately 52% of the total work-related fatality problem. Work-related bystander deaths are a major contributor to work-related injury in New Zealand, the majority occurring in the context of road traffic crashes. These deaths deserve more attention than they have received to date.


Prevalence of Anemia and Hemoglobin Disorders Among School Children in Myanmar.
The prevalence of anemia is high in the population of Myanmar and hypochromic microcytic anemia (HMA) is predominant. The objective of our study was to determine the prevalence of anemia and causes of HMA among school children. A cross-sectional study was conducted on 239 children from Thanlyin and Insein Townships, Yangon Region, Myanmar. Complete blood count (CBC) and blood film morphology was examined on venous blood samples. Hypochromic microcytic anemia cases were subsequently analyzed for serum ferritin and cellulose acetate hemoglobin (Hb) electrophoresis. The prevalence of anemia was 46.4%; 27.6% had mild, while 18.8% had moderate anemia, and no case of severe anemia was detected. The mean Hb concentration was 11.7 ± 0.9 g/dL. The younger age group (8-11 years) had a significantly higher prevalence of anemia than the older age group (12-15 years) (p = 0.029). Blood film morphology revealed a 50.6% red blood cell (RBC) disorder; HMA was the most common type (70.2%). Out of 85 children with HMA, three children (3.5%) had iron deficiency and all had comorbidity with Hb AE (βA/βE) (Hb E trait). Hemoglobin electrophoresis illustrated that Hb AA (βA/βA) (31, 36.5%) and Hb AE (βA/βE) trait (31, 36.5%) were the most common types followed by β-thalassemia (β-thal) trait (19, 22.3%) and Hb EE (βE/βE) (homozygous Hb E; HBB: c.79G>A) (three, 3.5%). Hematocrit [or packed cell volume (PCV)], mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC), showed a significant difference between Hb AE, Hb EE and β-thal trait (p = 0.029, 0.023, 0.015 and 0.01, respectively). Our findings will provide valuable information for the management of anemia in the Myanmar school-age population.


Dose-response in the treatment of breast cancer: a critical review.
In animal tumor models the dose-response curve for cytotoxic agents, especially cyclophosphamide, may be steep, but the slope and shape of this curve depends not only on the drug used but on the schedule of drug administration, the specific tumor type, tumor cell kinetics, and tumor mass. It might be anticipated from these studies that the human tumors most sensitive to dose effects would be leukemia, lymphoma, small-cell carcinoma of the lung, and testicular tumors rather than the low growth fraction, relatively less responsive tumors such as breast cancer. However, the clinical evidence for a steep dose-response curve in any tumor type is limited. For breast cancer such evidence is largely retrospective or derived from uncontrolled trials. The data available from randomized trials makes it seem unlikely that small, or even moderate, reductions in drug dose for nontrivial reasons will compromise the survival of patients with either early or metastatic disease. In spite of promising data from small trials, there is, as yet, inadequate evidence to justify the use of very-high-dose therapy and autologous marrow transplant outside the setting of a well-designed clinical trial. The value of high-dose therapy, intensive dose rate, and cumulative drug dose should each be studied in randomized controlled trials.


[Identification of congenital adrenal hyperplasia by measurement of blood-spot 17-hydroxyprogesterone].
Identification of congenital adrenal hyperplasia by measurement of blood-spot 17-hydroxyprogesterone. 21-hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH). The simplest way to diagnose the disease is the measurement of 17-hydroxyprogesterone level in the serum. The aim of the study was to analyze the clinical advantages of a centralized diagnostic strategy in Hungary using measurement of 17-hydroxyprogesterone in dried blood spots. During a 20 years period blood-spot samples of 1837 patients suspected to have CAH have been investigated. 185 patients proved to have CAH (classic 21-OHD 155; NCAH 27; 11beta-OHD 3 patients). A national database for CAH was set up by collecting further information about CAH patients in the country. Based on the frequency of the disease in girls during the nineties, the incidence of classical 21-OHD was calculated to be 1:11,147 in Hungary. Early diagnosis, optimal medical and surgical treatment, and attention to compliance may lead to further decrease in morbidity and mortality of CAH patients.


Hydrophobic handoff for direct delivery of peroxisome tail-anchored proteins.
Tail-anchored (TA) proteins are inserted into membranes post-translationally through a C-terminal transmembrane domain (TMD). The PEX19 protein binds peroxisome TA proteins in the cytoplasm and delivers them to the membrane through the PEX3 receptor protein. An amphipathic segment in PEX19 promotes docking on PEX3. However, how this leads to substrate insertion is unknown. Here we reconstitute peroxisome TA protein biogenesis into two sequential steps of substrate TMD engagement and membrane insertion. We identify a series of previously uncharacterized amphipathic segments in PEX19 and identify one whose hydrophobicity is required for membrane insertion, but not TMD chaperone activity or PEX3 binding. A membrane-proximal hydrophobic surface of PEX3 promotes an unconventional form of membrane intercalation, and is also required for TMD insertion. Together, these data support a mechanism in which hydrophobic moieties in the TMD chaperone and its membrane-associated receptor act in a concerted manner to prompt TMD release and membrane insertion.


Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats.
Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague‑Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14‑20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3β‑hydroxysteroid dehydrogenase (3β‑HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side‑chain cleavage enzyme and steroid 17 alpha‑hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3β‑HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4‑hydroxynonenalwere dose‑dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin‑like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3β‑HSD may be associated with impairment of the steroidogenic capacity.


Inactivation of Escherichia coli glycerol kinase by 5'-[p-(fluorosulfonyl)benzoyl]adenosine: protection by the hydrolyzed reagent.
Incubation of Escherichia coli glycerol kinase (EC 18.104.22.168; ATP:glycerol 3-phosphotransferase) with 5'-[p-(fluorosulfonyl)benzoyl]adenosine (FSO2BzAdo) at pH 8.0 and 25 degrees C results in the loss of enzyme activity, which is not restored by the addition of beta-mercaptoethanol or dithiothreitol. The FSO2BzAdo concentration dependence of the inactivation kinetics is described by a mechanism that includes the equilibrium binding of the reagent to the enzyme prior to a first-order inactivation reaction in addition to effects of reagent hydrolysis. The hydrolysis of the reagent has two effects on the observed kinetics. The first effect is deviation from pseudo-first-order kinetic behavior due to depletion of the reagent. The second effect is the novel protection of the enzyme from inactivation due to binding of the sulfonate hydrolysis product. The rate constant for the hydrolysis reaction, determined independently from the kinetics of F- release, is 0.021 min-1 under these conditions. Determinations of the reaction stoichiometry with 3H-labeled FSO2BzAdo show that the inactivation is associated with the covalent incorporation of 1.08 mol of reagent/mol of enzyme subunit. Ligand protection experiments show that ATP, AMP, dAMP, NADH, 5'-adenylyl imidodiphosphate, and the sulfonate hydrolysis product of FSO2BzAdo provide protection from inactivation. The protection obtained with ATP is not dependent on Mg2+. Less protection is obtained with glycerol, GMP, etheno-AMP, and cAMP. No protection is obtained with CMP, UMP, TMP, etheno-CMP, GTP, or fructose 1,6-bisphosphate. The results are consistent with modification by FSO2BzAdo of a single adenine nucleotide binding site per enzyme subunit.


Glial dysfunction and persistent neuropathic postsurgical pain.
Acute pain in response to injury is an important mechanism that serves to protect living beings from harm. However, persistent pain remaining long after the injury has healed serves no useful purpose and is a disabling condition. Persistent postsurgical pain, which is pain that lasts more than 3 months after surgery, affects 10-50% of patients undergoing elective surgery. Many of these patients are affected by neuropathic pain which is characterised as a pain caused by lesion or disease in the somatosensory nervous system. When established, this type of pain is difficult to treat and new approaches for prevention and treatment are needed. A possible contributing mechanism for the transition from acute physiological pain to persistent pain involves low-grade inflammation in the central nervous system (CNS), glial dysfunction and subsequently an imbalance in the neuron-glial interaction that causes enhanced and prolonged pain transmission. This topical review aims to highlight the contribution that inflammatory activated glial cell dysfunction may have for the development of persistent pain. Relevant literature was searched for in PubMed. Immediately after an injury to a nerve ending in the periphery such as in surgery, the inflammatory cascade is activated and immunocompetent cells migrate to the site of injury. Macrophages infiltrate the injured nerve and cause an inflammatory reaction in the nerve cell. This reaction leads to microglia activation in the central nervous system and the release of pro-inflammatory cytokines that activate and alter astrocyte function. Once the astrocytes and microglia have become activated, they participate in the development, spread, and potentiation of low-grade neuroinflammation. The inflammatory activated glial cells exhibit cellular changes, and their communication to each other and to neurons is altered. This renders neurons more excitable and pain transmission is enhanced and prolonged. Astrocyte dysfunction can be experimentally restored using the combined actions of a μ-opioid receptor agonist, a μ-opioid receptor antagonist, and an anti-epileptic agent. To find these agents we searched the literature for substances with possible anti-inflammatory properties that are usually used for other purposes in medicine. Inflammatory induced glial cell dysfunction is restorable in vitro by a combination of endomorphine-1, ultralow doses of naloxone and levetiracetam. Restoring inflammatory-activated glial cells, thereby restoring astrocyte-neuron interaction has the potential to affect pain transmission in neurons. Surgery causes inflammation at the site of injury. Peripheral nerve injury can cause low-grade inflammation in the CNS known as neuroinflammation. Low-grade neuroinflammation can cause an imbalance in the glial-neuron interaction and communication. This renders neurons more excitable and pain transmission is enhanced and prolonged. Astrocytic dysfunction can be restored in vitro by a combination of endomorphin-1, ultralow doses of naloxone and levetiracetam. This restoration is essential for the interaction between astrocytes and neurons and hence also for modulation of synaptic pain transmission. Larger studies in clinical settings are needed before these findings can be applied in a clinical context. Potentially, by targeting inflammatory activated glial cells and not only neurons, a new arena for development of pharmacological agents for persistent pain is opened.


Post concussion syndrome ebb and flow: longitudinal effects and management.
This research identified persistent post concussion symptoms (PCS) in a group of 20 adult subjects. PCS generally lasted for two years with a mean of 3.35 years. Typical symptoms included physical and cognitive fatigue, depressive behaviors, sensitivity to noise, social withdrawal, irritability, concentration and problem solving difficulties, loss of libido and much difficulty making decisions at even the simplest strategic level. They represented a hard core group for whom the original symptoms persisted well beyond the 6~month period. Participants identified their PCS according to sensory, somatic affective and cognitive items immediately following their trauma (01) and two years later (02). Counseling and psychotherapy intervention took place between 01 and 02. Items on the PCS schedules and the Beck Depression Inventory (II) demonstrated significant decline in the presence of overall symptoms most noticeably in reduction of agitation, irritability and suicidal wishes. However, subjects throughout generally experienced the feeling that they were being punished which equated with behaviors comparable with learned helplessness. The PCS group considered themselves to be different people after trauma. They had different goals, changing lifestyle, relationships and employment and were more often in a dependent state. Comparability with other conditions such as PTSD and chronic fatigue syndrome (CFS) was demonstrated by individuals who experienced persistent and invasive post concussion symptoms.


[Surgical treatment of arteriovenous malformations].
MAV surgery remains still today one of most difficult in the surgery of vascular malformations. Embolisation the most selective possible follow-up of a surgical removal carrying the totality of the nidus is the only effective treatment. Usually, MAV of small size, quiescent, should not be operated, the surgery being reserved for the evolutionary or complicated forms. This surgical procedure must allow the complete eradication of the lesion without which the cure is not possible. The incomplete removal causes repetition, sometimes aggravation with, sometimes, life threatening problems.


A meta-analysis of the effects of climate change on the mutualism between plants and arbuscular mycorrhizal fungi.
Climate change and other anthropogenic activities have the potential to alter the dynamics of resource exchange in the mutualistic symbiosis between plants and mycorrhizal fungi, potentially altering its stability. Arbuscular mycorrhizal (AM) fungi, which interact with most plant species, are less cold-tolerant than other groups of fungi; warming might therefore lead to increased fungal-mediated nutrient transfers to plants, which could strengthen the mutualism. By stimulating photosynthesis, rising CO2 could reduce the carbon cost of supporting AM fungi, which may also strengthen the mutualism. Furthermore, rising temperature and CO2 could have stronger effects on the mutualism in wild plants than in domesticated plants because the process of domestication can reduce the dependence of plants on mycorrhizal fungi. We conducted a multi-level random effects meta-analysis of experiments that quantified the strength of the mutualism as plant growth response to AM fungal inoculation (i.e., mycorrhizal growth response) under contrasting temperature and CO2 treatments that spanned the Last Glacial Maximum (LGM) to those expected with future climate change. We tested predictions using a three-level mixed effects meta-regression model with temperature or CO2, domestication status and their interaction as moderators. Increases from subambient to ambient temperature stimulated mycorrhizal growth response only for wild, but not for domesticated plant species. An increase from ambient to superambient temperature stimulated mycorrhizal growth response in both wild and domesticated plants, but the overall temperature effect was not statistically significant. By contrast, increased CO2 concentration, either from subambient to ambient or ambient to super ambient levels, did not affect mycorrhizal growth response in wild or domesticated plants. These results suggest the mutualism between wild plants and AM fungi was likely strengthened as temperature rose from the past to the present and that forecasted warming due to climate change may have modest positive effects on the mutualistic responses of plants to AM fungi. Mutualistic benefits obtained by plants from AM fungi may not have been altered by atmospheric CO2 increases from the past to the present, nor are they likely to be affected by a forecasted CO2 increase. This meta-analysis also identified gaps in the literature. In particular, (i) a large majority of studies that examined temperature effects on the mutualism focus on domesticated species (>80% of all trials) and (ii) very few studies examine how rising temperature and CO2, or other anthropogenic effects, interact to influence the mutualism. Therefore, to predict the stability of the mycorrhizal mutualism in the Anthropocene, future work should prioritize wild plant species as study subjects and focus on identifying how climate change factors and other human activities interact to affect plant responses to AM fungi.


Occurrence of two forms of H2M2 isoenzyme of lactate dehydrogenase.
Serum from healthy human subjects and serum from animals demonstrated a splitting of the H2M2 isoenzyme fraction of lactate dehydrogenase (LDH) into two subbands on polyacrylamide gel electrophoresis. These subbands were designated H2M2-a and H2M2-b, based on their relative electrophoretic mobilities, with the H2M2-a band being more anodal. The doublet of the H2M2 band was also demonstrated in human erythrocytes and in the hybridization mixture from porcine LDH, indicating the production of two forms of H2M2 isoenzyme in tissues. Supportive evidence for the presence of two H2M2 subforms was obtained by ion-exchange chromatography of the hybridization mixture. The recombination experiments of LDH-binding IgA with both normal human serum and LDH M subunit variant serum indicated the difference of molecular structure between the two subforms. On the basis of the results obtained in this study, a theoretical model of the probable molecular structure of LDH isoenzymes is proposed which could account for both the occurrence of two subforms of H2M2 and their selective binding to LDH-linking IgA.


Unusual intracytoplasmic inclusions in acute myeloblastic leukemia.
Unusual intracytoplasmic inclusions within early granulocyte precursor cells from a patient with acute myeloblastic leukemia (AML) are described. Based upon their staining characteristics and electron- and light-microscopic appearance, the inclusions are distinctly different from any previously described. The inclusions display a variety of shapes, including rectangles, squares, circles, ovals, and irregular, globular forms. Most of the inclusions are refractile and crystal-like. The possible composition of these inclusions is discussed. They are compared with inclusions previously described within leukemic and granulocytic cells.


Exploring the perceived met and unmet need of life-limited children, young people and families.
This article presents an original study commissioned by the UK charity, Together for Short Lives which explored children and young people up to 25 years of age with life-threatening/limiting conditions and their families. Using Appreciative Inquiry and framework analysis, qualitative work sought to explore perceived met and unmet needs of services and care. Fifty-one families were interviewed from one UK area, 18 of which were children/young people up to 25 years old. Findings indicated that children and their families felt medical/nursing needs were well met but provision was needed for broader financial, social and emotional support alongside more responsive specialist therapies.


Influence of software upgrade on detection of localized nerve fiber defects with the RTVue optical coherence tomograph in glaucoma.
To investigate the influence of a software version upgrade of the RTVue-100 Fourier-domain optical coherence tomograph (RTVue-OCT) on the detection of localized retinal nerve fiber layer (RNFL) defects in glaucoma. In software version 4.0 of RTVue-OCT 16, 22.5o-sized RNFL sectors are compared to the normative database, respectively, while in the 6.3 version, 8 45o-sized RNFL sectors are investigated and compared to the same normative database. We investigated data of 56 glaucomatous eyes with one or more localized RNFL defects found using software version 4.0, and reanalyzed them using software version 6.3. A corresponding localized visual field defect was seen for all localized RNFL defects. We found 37 RNFL defects which extended to only one 22.5o-sized sector surrounded by an area labeled as within normal limits. Six of them (3 classified as borderline and 3 as outside normal limits by software version 4.0) were classified as within normal limits when they were analyzed with software version 6.3. The other 31 focal RNFL defects and all wider localized RNFL defects which extended to 2 neighboring 22.5o-sized sectors were detected with both software versions. A software upgrade of the RTVue-OCT, which doubles the size and reduces the number of RNFL sectors, decreases the probability of detection of narrow focal RNFL defects in glaucoma. RTVue-OCT users need to know this, and in order to detect localized RNFL thinning in glaucoma they should rely on other features of the report.


[Psychotherapy for sexual dysfunctions and desire disorders].
Sexual problems do not always require specific psychotherapy. If missing or wrong sexual information is the main cause, sexual counselling can be sufficient. We define "sex-psychotherapy" as the methods which are based on Masters and Johnson as well as other symptom-focused and experience- oriented (exercise) psychotherapeutic methods for sexually disturbed couples and singles. These methods have significantly improved the treatment of sexual dysfunctions. In group- and in couple-settings they have proven to be effective in reducing sexual symptoms and improving sexual satisfaction and partnership-satisfaction. Long-term studies showed that sex-psycho- therapy leads to a stable improvement in sexual satisfaction, whereas the reduction of sexual symptoms is less stable. Therefore sex-psychotherapy should be combined with "relapse-prevention" methods. A number of sexual disorders are caused by psychological and organic factors; they need both psychotherapy and medical treatment. This is of special importance in elderly men and in women with symptoms of dyspareunia.


Smoothly graded Ca2+ release from inositol 1,4,5-trisphosphate-sensitive Ca2+ stores.
Stimulation of cells with Ca(2+)-mobilizing hormones often leads to the generation of temporally and spatially complex changes in the intracellular Ca2+ ion concentration ([Ca2+]i). To understand the mechanisms regulating Ca2+ release from intracellular stores more clearly, we investigated the ability of histamine to release Ca2+ stores under different experimental conditions, using video imaging of single Fura-2-loaded HeLa cells. In Ca(2+)-free medium, stepwise increases in histamine concentration released an increasing proportion of the intracellular Ca2+ pool. This pattern of Ca2+ release is analogous to the "quantal" release of Ca2+ previously observed using permeabilized cells. Quantal Ca2+ release was observed at both 20 and 37 degrees C and was not due to inactivation or desensitization of the Ca2+ release mechanism, since application of histamine in a pulsatile manner, which avoided desensitization of the Ca(2+)-release mechanism, still produced a quantal response. In Ca(2+)-containing medium at both 20 and 37 degrees C, stepwise increases in histamine concentration evoked [Ca2+]i responses where the amplitude was smoothly graded in direct proportion to the histamine concentration. Similar smoothly graded responses were observed from HeLa cells in Ca(2+)-free medium. These data indicate that hormone-evoked Ca2+ release from intracellular stores is limited by the hormone concentration, and that the mechanisms underlying complex [Ca2+]i signals do not lead to an all-or-none release of Ca2+ from the entire intracellular Ca2+ pool. We suggest that the hormone-sensitive intracellular Ca2+ pool is composed of functionally discrete units that are recruited by agonists in a concentration-dependent manner.


In vitro inactivation of SARS-CoV-2 by ozonated water via novel hand hygiene device.
The COVID-19 pandemic has heightened awareness of the need for novel surface disinfectants and hand-hygiene modalities. Ozone gas is an effective surface disinfectant, but toxicity limits its use in human applications. Ozonated water is a safer means to use ozone for disinfection, especially for human antisepsis. However, there are little data available regarding the effectiveness of ozonated water in eliminating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study utilizes a novel hand hygiene device that produces a stable ozone concentration of 0.5 +/-0.1 ppm in water and applies it using a proprietary spray that controls droplet size, velocity, and direction. The Device was used to apply ozonated water to a known quantity of SARS-CoV-2 Delta Variant viral particles on a non-porous surface (glass) for seven seconds. Post-exposure growth was compared to the unexposed matched control utilizing the Spearman-Karber method. Compared to control, ozonated water decreased SARS-CoV-2 viral growth by a mean log10 reduction of 4.33, or >99.99% reduction. These results suggest that the ozonated water, when applied by a spray hand hygiene device, is highly effective at surface disinfection of SARS-CoV-2.