Serum interleukin 6 (IL-6) - effect of surgery and under-nutrition.
We aimed to investigate the role of IL-6 as a mediator of the acute phase response (APR) in man; to assess the effect of under-nutrition on serum/plasma IL-6 levels; and to assess the value of IL-6 as a prognostic indicator by measuring IL-6 in timed venous samples taken from surgical patients and from protein deficient and control rats post-turpentine injections. Serum IL-6 rose in all surgical patients within 2-4h of incision. Peak levels differed among the groups and correlated significanlly with duration of surgery (r = 0.75, p<0.001). CRP did not rise in some patients and discriminated poorly among the groups. Patients who developed complications had higher IL-6 values at 24h post-incision than those making uneventful recoveries. Protein depleted rats had a significantly slower IL-6 response than controls. Serum IL-6 is a sensitive, early marker of tissue damage which might help to predict the development of surgical complications. Under-nutrition affects the IL-6 response in rats and may do so in man.


rAAV8 and rAAV9-Mediated Long-Term Muscle Transduction with Tacrolimus (FK506) in Non-Human Primates.
To establish an efficient, safe immunosuppressive regimen of adeno-associated vector (AAV)-mediated gene therapy for Duchenne muscular dystrophy (DMD), we evaluated the effect of tacrolimus (FK506) on skeletal muscle transduction with AAV8 and AAV9 vectors expressing the LacZ and microdystrophin (M3) genes labeled by FLAG. We utilized 3- to 4-year-old Macaca fascicularis, screened for neutralizing antibodies against AAV. 3 days before AAV injection and throughout the experiment, 0.06 mg/kg tacrolimus was intravenously administered. A viral suspension of 1 × 1013 viral genomes/muscle was intramuscularly injected bilaterally at the tibialis anterior and biceps brachii muscles, which were biopsied at 8, 16, 24, and 42 weeks after injection. Without tacrolimus, AAV8- and AAV9-mediated LacZ expression disappeared 8 and 16 weeks after transduction, respectively. With tacrolimus, AAV8/9-mediated LacZ expression persisted for at least 42 weeks after injection. At 42 weeks after AAV8CMVLacZ and AAV9CMVLacZ injection, nearly 50% and 17% of muscle fibers were positive for β-galactosidase, respectively. AAV8/9-mediated M3-FLAG expression lasted for up to 42 weeks using tacrolimus. No significant generalized toxicity was observed in any monkey. These results indicate that tacrolimus administration regulated the immune response to transgenes and truncated microdystrophin in normal primates and may enhance the benefits of AAV-mediated gene therapy for DMD.


Mitochondrial dysfunction induced by Bisphenol A is a factor of its hepatotoxicity in rats.
Bisphenol A (BPA), an estrogenic and endocrine disrupting agent, is widely used in manufacturing of polycarbonate plastics and epoxy resins. BPA and other endocrine disrupting chemicals (EDCs) act via multiple mechanisms including interference with mitochondrial functions. Mitochondria are the hub of cellular energy pool and hence are the target of many EDCs. We studied perturbation of activities of mitochondrial enzymes by BPA and its possible role in hepatotoxicity in Wistar rats. Rats were exposed to BPA (150 mg/kg, 250 mg/kg, 500 mg/kg per os, for 14 days) and activities of enzymes of mitochondrial electron transport chain (ETC) were measured. Besides, other biochemical parameters such as superoxide generation, protein oxidation, and lipid peroxidation (LPO) were also measured. Our results indicated a significant decrease in the activities of enzymes of mitochondrial ETC complexes, i.e., complex I, II, III, IV, and V along with significant increase in LPO and protein oxidation. Additionally, a significant increase in mitochondrial superoxide generation was also observed. All these findings could be attributed to enhanced oxidative stress, decrease in reduced glutathione level, and decrease in the activity of superoxide dismutase in rat liver mitochondria isolated from BPA-treated rats. BPA treatment also caused a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase indicating its potential hepatotoxicity. Furthermore, histopathological findings revealed marked edema formation, hepatocellular degeneration, and necrosis of liver tissue in BPA-exposed rats. In conclusion, this study provides an evidence of impaired mitochondrial bioenergetics and liver toxicity after high-dose BPA exposure in rats. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1922-1934, 2016.


Effect of pentobarbital on the disposition of alprenolol.
Alprenolol was administered orally and intravenously to 5 healthy subjects before and after 10 to 14 daily doses of 0.1 gm pentobarbital. The area under the plasma concentration time curve after an oral 200-mg dose decreased from 706 +/- 277 to 154 +/- 48 ng/ml-hr (mean and SD) with the barbiturate treatment, but there was no significant change in elimination rate. The change in area corresponded to an increase in extraction by the liver from 0.72 +/- 0.13 to 0.93 +/- 0.01. The disposition of a 5.0-mg intravenous dose of alprenolol did not change significantly after pentobarbital treatment. There was no indication of a marked change in hepatic blood flow estimated from the clearance of alprenolol after intravenous administration. It is concluded that pentobarbital administration induces the metabolism of alprenolol in man and that the pharmacokinetic theories derived for hepatic extraction of drugs subject to a high metabolic clearance can be successfully applied.


Effects of oxygen radicals, hydrogen peroxide and water-soluble singlet oxygen carriers on 5- and 12-lipoxygenase.
Inhibition of 5-lipoxygenase from bovine polymorphonuclear leukocytes and 12-lipoxygenase from bovine platelets by active oxygen species has been studied. Oxygen radicals and hydrogen peroxide markedly inhibited 12-lipoxygenase, whereas 5-lipoxygenase activity was only moderately influenced. Singlet oxygen liberated from water-soluble naphthalene endoperoxides was without effect.


[The presence of 6-oxo-PGF1alpha and thromboxane B2 in peritoneal exudates released by iota-carrageenan in the rat].
The wash fluid of the peritoneal cavity of the rat contains large amounts of 6-oxo PGF1 alpha. The peritoneal exudate induced two hours previously by iota carrageenan contains thromboxane B2 but its level in 6-oxo PGF1 alpha is not increased.


Use of rivaroxaban in an elderly patient with intermediate-low early mortality risk due to pulmonary embolism: a case report.
Pulmonary embolism remains one of the leading causes of cardiovascular mortality. The standard treatment for pulmonary embolism is anticoagulant therapy using low molecular weight heparin, fondaparinux and a vitamin K antagonist, but a recent clinical trial showed that rivaroxaban, an oral factor Xa inhibitor, was as effective as standard therapy for the initial and long-term treatment of pulmonary embolism and had less bleeding complications. The present report describes the case of an 80-year-old white man with an intermediate to low early mortality risk of pulmonary embolism. He was successfully treated with rivaroxaban (administered orally as monotherapy), demonstrating rapid benefit without any adverse events. Rivaroxaban, particularly in the acute phase of pulmonary embolism, may be considered an effective and safe therapeutic choice even in elderly patients, a population less represented in clinical trials.


Characterization of serological cross-reactivity between polysaccharide antigens of Streptococcus mutans serotypes c and d.
Immunological assays with antisera prepared against purified Streptococcus mutans serotype c polysaccharide demonstrated that a cross-reacting determinant on c polysaccharide reacted with the wall-associated rhamnose-glucose polysaccharide from S. mutans serotype d. Studies with 60 antisera prepared against chemostat cultures of S. mutans Ingbritt (c) demonstrated that the rhamnose-glucose polysaccharide cross-reactive determinant was consistently expressed on c antigen under a variety of growth conditions.


Perinatal Nicotine Reduces Chemosensitivity of Medullary 5-HT Neurons after Maturation in Culture.
Perinatal exposure to nicotine produces ventilatory and chemoreflex deficits in neonatal mammals. Medullary 5-HT neurons are putative central chemoreceptors that innervate respiratory nuclei and promote ventilation, receive cholinergic input and express nicotinic acetylcholine receptors (nAChRs). Perforated patch clamp recordings were made from cultured 5-HT neurons dissociated from the medullary raphé of 0-3 day old mice expressing enhanced yellow fluorescent protein driven by the enhancer region for PET1 (ePet-EYFP). The effect of exposure to low (6 mg kg-1day-1) or high (60 mg kg-1day-1) doses of nicotine in utero (prenatal), in culture (postnatal), or both and the effect of acute nicotine exposure (10 μM), were examined on baseline firing rate (FR at 5% CO2, pH = 7.4) and the change in FR with acidosis (9% CO2, pH 7.2) in young (12-21 days in vitro, DIV) and older (≥22 DIV) acidosis stimulated 5-HT neurons. Nicotine exposed neurons exhibited ∼67% of the response to acidosis recorded in neurons given vehicle (p = 0.005), with older neurons exposed to high dose prenatal and postnatal nicotine, exhibiting only 28% of that recorded in the vehicle neurons (p < 0.01). In neurons exposed to low or high dose prenatal and postnatal nicotine, acute nicotine exposure led to a smaller increase in FR (∼+51% vs +168%, p = 0.026) and response to acidosis (+6% vs +67%, p = 0.014) compared to vehicle. These data show that exposure to nicotine during development reduces chemosensitivity of 5-HT neurons as they mature, an effect that may be related to the abnormal chemoreflexes reported in rodents exposed to nicotine in utero, and may cause a greater risk for sudden infant death syndrome (SIDS).


Forecasting of the SARS-CoV-2 epidemic in India using SIR model, flatten curve and herd immunity.
In this paper, we are presenting an epidemiological model for exploring the transmission of outbreaks caused by viral infections. Mathematics and statistics are still at the cutting edge of technology where scientific experts, health facilities, and government deal with infection and disease transmission issues. The model has implicitly applied to COVID-19, a transmittable disease by the SARS-CoV-2 virus. The SIR model (Susceptible-Infection-Recovered) used as a context for examining the nature of the pandemic. Though, some of the mathematical model assumptions have been improved evaluation of the contamination-free from excessive predictions. The objective of this study is to provide a simple but effective explanatory model for the prediction of the future development of infection and for checking the effectiveness of containment and lock-down. We proposed a SIR model with a flattening curve and herd immunity based on a susceptible population that grows over time and difference in mortality and birth rates. It illustrates how a disease behaves over time, taking variables such as the number of sensitive individuals in the community and the number of those who are immune. It accurately model the disease and their lessons on the importance of immunization and herd immunity. The outcomes obtained from the simulation of the COVID-19 outbreak in India make it possible to formulate projections and forecasts for the future epidemic progress circumstance in India.


Localization in platelets of sodium 51Cr-chromate, 125I-antibody to whole membrane, and 3H-diisopropylfluorophosphate using electron microscopic autoradiography.
Platelets from the rabbit and rat, respectively, were incubated with sodium 51Cr-chromate and 3H-diisopropylfluorophosphate (3H-DFP) in the same manner as for platelet survival studies. A third isotope, 125I, was incorporated into a labeled antibody raised against a partially purified pig platelet membrane fraction. The 51Cr label was found to be concentrated predominantly in the cytoplasm, with a marked degree of association with mitochondria, whereas the tritium label appeared to be largely confined to the periphery of the platelet, particularly in association with the open canalicular system. The 125I-labeled antibody showed a very marked association with the plasma membrane and the open canalicular system, suggesting a membrane-bound affinity.


Pregnancy and Naltrexone Pharmacotherapy.
A 25-year-old woman, gravida 3 para 2 at 12 weeks of gestation, with two prior cesarean deliveries, presents for prenatal care. She is in treatment for opioid use disorder on extended-release naltrexone injection, with a history of opioid overdose, relapse, and poor treatment adherence on methadone and buprenorphine. She asks, "Is it safe for my baby if I continue on this medication? How will you manage my postoperative pain?"


Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study.
The objective of this study was to encapsulate the antibacterial drug levofloxacin hemihydrate (LF) into spanlastics (SLs) followed by incorporation into gelrite in situ gel to enhance its antibacterial activity and sustain ocular delivery. A combination of Span 60 as main vesicle component and Tweens as an edge activator (EA) was used to prepare SLs using the thin film hydration method. A 32 factorial design was applied to study the effect of formulation variables (ratio of Span 60: EA and type of EA) on SLs characteristics (encapsulation efficiency (EE%), particle size (PS), zeta potential (ZP) and percentage of drug released). In-vitro antimicrobial study was conducted to determine the antibacterial activity of the optimized formula. Finally confocal laser scanning microscopy (CLSM) was applied to monitor SLs corneal penetration. The optimum formulation (F5), contains 240 mg Span 60 and 60 mg Tween 60 as EA. F5 exhibited EE% = 59.7 ± 4.2%, PS = 177.6 ± 1.8 nm, PDI = 0.27 ± 0.022 and ZP = -40.6 ± 0.68 mV. Furthermore, only 39.37 ± 0.72% of LF amount was released after 4 h compared to complete release from drug solution. The apparent permeation coefficient was (14.7 × 10-3 cm/h) compared to (9.7 × 10-3 cm/h) for LF solution. Moreover, F5 exhibited 200% and 100% increase in the antibacterial efficacy against Pseudomonas aeruginosa and Staphylococcus aureus respectively.


Rectal irrigation as rescue therapy for refractory and severe hemorrhagic radiation proctitis: A case report.
Rectal irrigation may be considered in refractory and severe hematochezia from chronic radiation proctitis before performing other invasive treatments. It prevents superimposed infection and effectively reduces bleeding.


Localization of the Na+-D-glucose cotransporter SGLT1 in the blood-brain barrier.
Immunoreactivity of the Na+-D-glucose cotransporter SGLT1 was demonstrated in intracerebral capillaries of rat and pig. Immunostaining suggested that SGLT1 is located in the luminal membrane of the endothelial cells and in intracellular vesicles. Using in situ hybridization, SGLT1 mRNA was not detectable in intracerebral capillaries of non-treated or sham-operated Wistar rats. However, 1 day after a transient occlusion of the right middle cerebral artery, SGLT1 mRNA was detected in capillaries of both brain hemispheres. Expression of SGLT1 was also demonstrated in primary cultures of capillary endothelial cells from pig using polymerase chain reaction after reverse transcription and western blotting. The data suggest that SGLT1 participates in transport of D-glucose across the blood-brain barrier and is upregulated after brain ischemia and reperfusion.


Rhabdoid type intramedullary meningioma. A case report and review of the literature.
Meningiomas are the most frequent tumors located at the spinal level together with neurinomas and metastases. These tumors tend to be intradural and extramedullar. There are few cases described in the literature with a purely intramedullary location (less than 10 cases) and they are frequently observed in the union craneal-cervical. In the presence of an intramedullary tumor we perform differential diagnoses with ependymomas, astrocytomas... In this article we present the first case described in the literature of a patient with a rabdoid-type meningioma exclusively intramedullary at the level of the medullary cone.


Quantal properties of H-type glutamatergic synaptic input to the striatal medium spiny neurons.
The striatal medium spiny neuron receives two distinct glutamatergic synaptic inputs, S-type and H-type inputs, which have very different amplitudes. We report here that peak amplitudes of unitary H-type excitatory postsynaptic currents (EPSCs) could be reduced by decreasing external Ca2+, unlike S-type EPSCs. This suggests that H-type EPSCs are multiquantal, and supports the idea that the cellular origin of H-type EPSCs is distinct from that of the S-type EPSCs.


Effects of carotid endarterectomy on blood flow in the internal carotid artery.
A retrospective study of patients operated upon for carotid stenosis was undertaken with special emphasis on the internal carotid artery (ICA) blood flow. A total of 212 endarterectomies were performed in 198 patients. The overall operative mortality was 1.4%, and the cerebral morbidity was 2.8%. A temporary inlying shunt was used routinely during endarterectomy. In two of 198 endarterectomies the shunt itself could not be excluded as a possible cause of postoperative neurological deficits. The ICA blood flow before and after endarterectomy was determined by electromagnetic flowmetry in 160 operations. Flow measurements were compared in TIA and stroke patients, in patients with high and low degrees of luminal constriction, and in patients with occluded or "open" (minimal stenosis) contralateral ICA. The results indicate that the preoperative blood flow, as well as the increase in blood flow after removal of the stenosis, is determined not only by the degree of luminal constriction, but also by the magnitude of blood flow from all precerebral feeding arteries and their intracranial collateral circulation. In treatment of carotid stenosis critical evaluation of symptoms, angiography, and haemodynamics are essential. Endarterectomy is beneficial because an embolic source is removed, and probably because perfusion is improved to areas of the brain with marginal circulation. The main factors regulating the normal cerebral perfusion are cardiac output (mean perfusion pressure), arterial pCO2 and PO2, haematocrit, and the arterial and venous blood pressures. Comparatively few investigations have been published on the effect of endarterectomy upon internal carotid artery (ICA) blood flow 4, 12, 14, 27. Since 1970 we have routinely measured the ICA blood flow before and after endarterectomy. This paper reviews the clinical and haemodynamic results of our patients operated on for carotid stenosis.


Activation of pyruvate dehydrogenase in the perfused rat liver by vasopressin.
The proportion of pyruvate dehydrogenase in its active form is doubled in rat liver within 5 min of addition of vasopressin to the perfusing medium.


Hemodynamic basis of the reduced oxygen uptake relative to work rate during incremental exercise in patients with chronic heart failure.
The ratio of the increase in oxygen uptake to the increase in work rate (DeltaVO2/DeltaWR) during incremental exercise is reduced in patients with severe chronic heart failure (CHF). However, the pathophysiological basis of the reduced O2 uptake relative to work rate has not been elucidated. To elucidate the hemodynamic basis of the reduced ratio of DeltaVO2/DeltaWR during exercise in severe CHF, 48 patients with CHF (15 patients in class I, 21 in class II and 12 in class III) performed maximal ergometer exercise with respiratory gas analysis. Cardiac output and systemic O2 extraction were measured at 1-min intervals during exercise. Both peak VO2 and peak cardiac output decreased as the severity of CHF advanced. Patients in class III showed significantly reduced DeltaVO2/DeltaWR than those in class I (8.2+/-0.9 vs. 9.8+/-1.5 ml/min/W, P<0.01). Cardiac output at rest was significantly lower, and O2 extraction at rest was significantly higher in class III than class I. The ratio of the increase in cardiac output to the increase in work rate (DeltaCO/DeltaWR) was significantly lower in class III than class I (42.5+/-14.5 vs. 60.6+/-10.3 ml/min/W), and the ratio of the increase in O2 extraction to the increase in work rate (DeltaO2 extraction/DeltaWR) was significantly higher in class III than class I (0.45+/-0.13 vs. 0.34+/-0.08%/W). The DeltaVO2/DeltaWR was significantly correlated with the DeltaCO/DeltaWR (r=0.67, P<0.01), and the DeltaCO/DeltaWR was inversely correlated with DeltaO2 extraction/DeltaWR (r=-0.65, P<0.01). Decreased O2 supply due to reduced cardiac output was not fully compensated by the increased O2 extraction. Reduced ratio of DeltaVO2/DeltaWR in advanced CHF reflected the severely attenuated cardiac output response to exercise.


Comparative analysis of homocysteine concentrations in patients with retinal vein occlusion versus thrombotic and atherosclerotic disorders.
The objectives of the present study were to determine the concentrations of plasma homocysteine in a large (n = 562) cohort of patients with retinal vein occlusion (RVO) and to compare them with the values observed in other vascular thrombotic and atherosclerotic conditions. Results were compared with those observed in patients with deep vein thrombosis (n = 1700), pulmonary embolism (n = 542), transient ischemic attack (n = 1301), cerebrovascular accident (n = 1299), myocardial infarction (n = 3087), as well as peripheral artery occlusive disease (n = 1946). No differences were found between the age-adjusted estimated marginal mean +/- SE for homocysteine concentrations in individuals with RVO and in those who had other atherosclerotic and atherothrombotic diseases The respective concentrations for RVO, deep vein thrombosis, pulmonary embolism, transient ischemic attack, cerebrovascular accident, myocardial infarction, and peripheral artery occlusive disease were 13.8 +/- 0.4, 14.7 +/- 0.3, 14.3 +/- 0.5, 14.2 +/- 0.3,14.6 +/- 0.3, 13.8 +/- 0.2, 14.4 +/- 0.2 pmol/l for men and 11.4 +/- 0.4, 10.7 +/- 0.2, 10.8 +/- 0.3, 10.8 +/- 0.2, 11.8 +/- 0.2, 11.2 +/- 0.2 pmol/l for women. In conclusion, the concentrations of homocysteine observed in patients with RVO are similar to those detected in other thrombotic and atherosclerotic vascular disorders. In view of the fact that this is a common disorder of the elderly, increased homocysteine concentrations often reported in patients with RVO could reflect the underlying atherothrombotic condition and might not necessarily be specifically related to the RVO per se. This information is relevant in researching the potential etiopathologic role, if any, of increased homocysteine concentrations in RVO.


Impacts of calcium peroxide on phosphorus and tungsten releases from sediments.
In this study, CaO2 was used as a capping material to control the release of Phosphate (P) and tungsten (W) from the sediment due to its oxygen-releasing and oxidative properties. The results revealed significant decreases in SRP and soluble W concentrations after the addition of CaO2. The mechanisms of P and W adsorption by CaO2 were mainly chemisorption and ligand exchange mechanisms. In addition, the results showed significant increases in HCl-P and amorphous and poorly crystalline(oxyhydr)oxides bound W after the addition of CaO2. The highest reduction rates of sediment SRP and soluble W release were 37 and 43%, respectively. Furthermore, CaO2 can promote the redox of iron (Fe) and manganese (Mn). On the other hand, a significant positive correlation was observed between SRP/soluble W and soluble Fe (II) and between SRP/soluble W and soluble Mn, indicating that the effects of CaO2 on Fe and Mn redox play a crucial role in controlling P and W releases from sediments. However, the redox of Fe plays a key role in controlling sediment P and W release. Therefore, CaO2 addition can simultaneously inhibit sediment internal P and W release.


Sustained suppression of HCV replication and inflammatory activity after interleukin-2 therapy in patients with HIV/hepatitis C virus coinfection.
There is increasing evidence that coinfection of hepatitis C (HCV) with HIV is associated with accelerated progression of liver cirrhosis. The aim of this pilot study was to investigate toxicity and efficacy of interleukin-2 (IL-2) for treatment of affected patients. Because low-dose, daily IL-2 therapy is well tolerated and can elevate CD4 cell counts and improve immune functions, patients were treated with 1-2 million units (MU) IL-2 subcutaneously daily. This pilot trial included 7 HIV/HCV-coinfected individuals. During therapy, clinical, virologic, and laboratory parameters were closely monitored. All patients responded to IL-2 therapy with either improvement of either CD4 cell counts or liver function test results. In 2 patients, HCV-RNA in serum became negative 2 and 4 months, respectively, after cessation of therapy. HCV-RNA has remained undetectable in these 2 patients for 18 and 24 months, respectively. Therapy was well tolerated and no grade III or IV toxicities were observed. Low-dose, daily IL-2 therapy can improve both CD4 cell counts and liver function test results in patients with HIV/HCV coinfection and may in some cases lead to sustained suppression of viremia of HCV.


Agency through medicalization: Ghanaian children navigating illness, medicine and adult resistance.
Medicalization in the Global North assumes that bottom-up medicalization is driven by increasing consumer power, risk avoidance among professionals, or emancipation. Building on ethnographic work of the first author, this article aimed to explore the existence and conditions of a different and novel mechanism and found children manifesting agency through self-medicalization. We look at how Ghanaian children pragmatically deal with everyday health concerns and argue children are agents of medicalization and medicalization enables agency in children. Through interpretive and collaborative content analysis of structured ethnographic observations of 105 children from different class backgrounds (between June 2016 and December 2017) we found children in Northern Ghana framed situations of feeling ill in markedly biomedical terms and persisted in biomedical treatment even with opposition from adults. We observed that children intentionally navigated opposition from adults, mobilized support through networks, exploited power differences between adults, and organized treatment among themselves if necessary. While girls had an even harder time to muster recognition from adults, we also discovered children from a lower socioeconomic background, with more experience on the street had more leeway in navigating lack of support. So far, children's agency in health and illness has only been discussed in instances where children had already received a professional diagnosis. In our case where children had not yet received a professional diagnosis, we find that agency is enabled through bodily awareness, experience, interactions with peers, family, and the media; all working as tools for children to self-diagnose and to deal with illness in a postcolonial setting.


Diffractaic acid, a novel TrxR1 inhibitor, induces cytotoxicity, apoptosis, and antimigration in human breast cancer cells.
Breast cancer represents one of the most frequently encountered cancer types among women worldwide. Thioredoxin reductase 1 (TrxR1) is a therapeutic target for breast cancer therapy due to its overexpression in tumor cells. The current research aims to determine the anticancer effect of diffractaic acid, a lichen acid, in breast cancer, and research whether the anticancer effect of diffractaic acid occurs through TrxR1 targeting. According to the XTT assay results, diffractaic acid induced cytotoxicity in both MCF-7 and MDA-MB-453 cells with IC50 values of 51.32 μg/ml and 87.03 μg/ml, respectively. Flow cytometry and cell migration analyses revealed the apoptotic, necrotic, and antimigratory effects of diffractaic acid. qPCR analysis indicated the upregulation of the BAX/BCL2 ratio and the P53 gene in MCF-7 cells with only the P53 gene in MDA-MB-453 cells. The gene, protein, and enzyme activity of TrxR1 were suppressed in MCF-7 cells, whereas only enzyme activity was suppressed in MDA-MB-453 cells. These findings illustrate the anticancer effect of diffractaic acid on breast cancer targeting TrxR1. In conclusion, these data reveal that diffractaic acid may be considered an effective therapeutic agent for breast cancer treatment.


[Catch-up growth in growth hormone deficit children treated with GH since the first year of life].
Long-term effects of growth hormone (GH) treatment were studied in 59 GH deficient (GHD) children, whose treatment was started before the age of 1 year, during the period 1978-1992, under the supervision of the France-Hypophyse Association. Mean duration of treatment was 8 +/- 3.6 years. At the last evaluation, 20 patients (34%) had a height above normal mean for age, and 50 (85%) had a height above the second lower standard deviation (SD) for age. Final height prediction performed in 29 patients was greater than target size (-0.35 +/- 1.4 SD vs -0.56 +/- 0.79 SD). These results show that early treatment of GHD infants allows normal statural growth in the majority of the cases; in addition, they underline the importance of early diagnosis of GH deficiency.


Synthesis of potential antioxidants by synergy of ultrasound and acidic graphene nanosheets as catalyst in water.
Efficient synthesis of a set of bisphenolic compounds, resulting from the incorporation of 2,4-dialkylphenols and aromatic or aliphatic aldehydes, allowed the discovery of new bisphenols with relative modest to good antioxidant activity. Bisphenolic compounds were prepared via easy and simple approach under ultrasound irradiation in water. Sulfonated graphene nanosheets were employed as a catalyst for the synthesis of bisphenolic compounds. These compounds were obtained in high to excellent yields (88-98%) and relatively short reaction times (4-20 min). Moreover, some of the synthetic compounds were investigated and revealed outstanding antioxidant activity, when examined by a 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) decolorization assay system. The proposed method has a novel viewpoint in the preparation of potential antioxidant compounds.


Plasma protease inhibitors in premature infants: influence of gestational age, postnatal age, and health status.
In newborn infants, the influence of gestational age (GA), postnatal age (PA), and health status on the plasma protease inhibitors alpha 2-macroglobulin (alpha 2-M), alpha 1-antitrypsin (alpha 1-AT), C1 esterase inhibitor (C1E-INH), alpha 2-antiplasmin (alpha 2-AP), and antithrombin III (AT-III) was investigated. Inhibitor levels were measured by radial-immunodiffusion and expressed as a percentage of pooled plasma from adults (mean +/- SEM). In total, 54 premature infants (28-36 weeks gestation) were classified at birth as healthy (N = 22) (IV fluids, antibiotics only) or sick (N = 32) (all other support, but excluding infants with disseminated intravascular coagulation (DIC] and studied on Days 1 and/or 7 of life. Healthy term infants (N = 18) and infants with DIC (N = 10) were studied on Day 1 only. All inhibitors except C1E-INH increased with increasing gestational age (P less than 0.01). In healthy premature infants all inhibitor levels reached the normal adult range by 1 week of age. In contrast, at 1 week of age, sick infants had lower levels of alpha 2-M and alpha 2-AP, and higher levels of alpha 1-AT compared to healthy infants (P less than 0.01). The presence of DIC depressed all of the inhibitors on Day 1 except alpha 1-AT when compared to healthy controls (P less than 0.01). Thus, gestational age, postnatal age, and health status all significantly influenced the levels of these plasma protease inhibitors.


Structural and genetic characterization of the Shigella boydii type 18 O antigen.
Shigella strains are important human pathogens and are normally identified by their O antigens. O antigen is an essential part of the lipopolysaccharide present in the outer membrane of Gram-negative bacteria and plays a role in pathogenicity. Structural and genetic organization of the Shigella boydii type 18 O antigen was investigated. As judged by sugar and methylation analyses and NMR spectroscopy data, the O antigen has a linear pentasaccharide repeating unit (O unit), which consists of three L-rhamnose residues, and one residue each of D-galacturonic acid (D-GalA) and N-acetylgalactosamine (D-GalNAc), and the following structure of the O unit was established. -->3)-beta-L-Rhap-(1-->4)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->2)-alpha-D-GalpA-(1-->3)-alpha-D-GalpNAc-(1--> The O antigen gene cluster of S. boydii type 18, which contains nine open reading frames (ORFs), was found between galF and gnd. Based on homology, all of the ORFs were identified as O antigen synthesis genes, involved in the synthesis of rhamnose, transfer of sugars, and processing of O unit. Genes specific for S. boydii type 18 were identified, which can be potentially used for the development of a PCR-based assay for the identification and detection of this strain.


Peptomeric analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds.
A series of linear and monocyclic analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds, modified by N-(4-aminobutyl)glycine (Nlys) and N-benzylglycine (Nphe), were obtained by the solid-phase method. Some of these peptomers displayed trypsin or chymotrypsin inhibitory activity. In contradiction to the literature data, in most analogues peptide bonds formed by these peptoid monomers were at least partially hydrolyzed by the experimental enzymes at two different pH (3.5 and 8.3). Nevertheless, the replacement of Phe present in the P(1) substrate specificity of linear inactive SFTI-1 analogue with Nphe, yielded a potent chymotrypsin inhibitor. The introduction of one cyclic element (a disulfide bridge or head-to-tail cyclization) to the analogues synthesized significantly increased their proteinase resistance.


Characterization of Immunoactive and Immunotolerant CD4+ T Cells in Breast Cancer by Measuring Activity of Signaling Pathways That Determine Immune Cell Function.
Cancer immunotolerance may be reversed by checkpoint inhibitor immunotherapy; however, only a subset of patients responds to immunotherapy. The prediction of clinical response in the individual patient remains a challenge. CD4+ T cells play a role in activating adaptive immune responses against cancer, while the conversion to immunosuppression is mainly caused by CD4+ regulatory T cell (Treg) cells. Signal transduction pathways (STPs) control the main functions of immune cells. A novel previously described assay technology enables the quantitative measurement of activity of multiple STPs in individual cell and tissue samples. The activities of the TGFβ, NFκB, PI3K-FOXO, JAK-STAT1/2, JAK-STAT3, and Notch STPs were measured in CD4+ T cell subsets and used to investigate cellular mechanisms underlying breast cancer-induced immunotolerance. STP activity scores were measured on Affymetrix expression microarray data of the following: (1) resting and immune-activated CD4+ T cells; (2) CD4+ T-helper 1 (Th1) and T-helper 2 (Th2) cells; (3) CD4+ Treg cells; (4) immune-activated CD4+ T cells incubated with breast cancer tissue supernatants; and (5) CD4+ T cells from blood, lymph nodes, and cancer tissue of 10 primary breast cancer patients. CD4+ T cell activation induced PI3K, NFκB, JAK-STAT1/2, and JAK-STAT3 STP activities. Th1, Th2, and Treg cells each showed a typical pathway activity profile. The incubation of activated CD4+ T cells with cancer supernatants reduced the PI3K, NFκB, and JAK-STAT3 pathway activities and increased the TGFβ pathway activity, characteristic of an immunotolerant state. Immunosuppressive Treg cells were characterized by high NFκB, JAK-STAT3, TGFβ, and Notch pathway activity scores. An immunotolerant pathway activity profile was identified in CD4+ T cells from tumor infiltrate and blood of a subset of primary breast cancer patients, which was most similar to the pathway activity profile in immunosuppressive Treg cells. Signaling pathway assays can be used to quantitatively measure the functional immune response state of lymphocyte subsets in vitro and in vivo. Clinical results suggest that, in primary breast cancer, the adaptive immune response of CD4+ T cells may be frequently replaced by immunosuppressive Treg cells, potentially causing resistance to checkpoint inhibition. In vitro study results suggest that this is mediated by soluble factors from cancer tissue. Signaling pathway activity analysis on TIL and/or blood samples may improve response prediction and monitoring response to checkpoint inhibitors and may provide new therapeutic targets (e.g., the Notch pathway) to reduce resistance to immunotherapy.


Standard reference values of the postural control in healthy female adults aged between 31 and 40 years in Germany: an observational study.
To detect deviations from a normal postural control, standard values can be helpful for comparison purposes. Since the postural control is influenced by gender and age, the aim of the present study was the collection of standard values for women between 31 and 40 years of age. For the study, 106 female, subjectively healthy, German subjects aged between 31 and 40 years (35 ± 2.98 years) were measured using a pressure measuring platform. Their average BMI was 21.60 ± 4.65 kg/m2. The load distribution between left and right foot was almost evenly balanced with a median 51.46% load on the left [tolerance interval (TR) 37.02%/65.90%; confidence interval (CI) 50.06/52.85%] and 48.54% [TR 43.10/62.97%; CI 47.14/49.93%] on the right foot. The median forefoot load was 33.84% [TR 20.68/54.73%; CI 31.67/37.33%] and the rearfoot load was measured at 66.16% [TR 45.27/79.33%; CI 62.67/68.33%]. The median/mean body sway in the sagittal plane was measured 12 mm [TR 5.45/23.44 mm; CI 11.00/14.00 mm] and 8.17 mm in the frontal plane [TR 3.33/19.08 mm; CI 7.67/9.33 mm]. The median of the ellipse area is 0.72 cm2 [TR 0.15/3.69 cm2; CI 0.54/0.89°]. The ellipse width has a median of 0.66 cm [TR 0.30/1.77 cm; CI 0.61/0.78 cm] and the height of 0.33 cm [TR 0.13/0.71 cm; CI 0.30/0.37 cm]. The ellipse angle (sway, left forefoot to right rearfoot) has a mean of - 19.34° [TR - 59.21/- 0.44°; CI - 22.52/- 16.16°] and the ellipse angle sway from right forefoot to left rearfoot has a mean of 12.75° [TR 0.09/59.09°; CI 9.00/16.33°]. The right-to-left ratio is balanced. The forefoot-to-rearfoot ratio is approximately 1:2. Also, the body sway can be classified with 12 and 8 mm as normal. The direction of fluctuation is either approx. 19° from the left forefoot to the right rearfoot or approx. 13° the opposite. Body weight, height, and BMI were comparable to the German average of women in a similar age group, so that the measured standard values are representative and might serve as baseline for the normal function of the balance system in order to support the diagnosis of possible dysfunctions in postural control.


Comparison and evaluation of four methods for extracting DNA from Giardia duodenalis cysts for PCR targeting the tpi gene.
Giardia duodenalis is an intestinal flagellated protozoan and the common cause of gastrointestinal diseases in human. This parasite can be seen in two different forms in its life cycle including as cyst and trophozoite. Due to presence of resistant cyst wall, DNA extraction inhibitors along with artifact in stool specimens, this study was performed aiming to evaluate four methods for DNA extraction from G. duodenalis cysts. Seventy G. duodenalis positive stool specimens that were confirmed by light microscope were included in this study. All stool samples were concentrated using four layered discontinuous sucrose flotation technique (0.5, 0.75, 1, and 1.5 M) and single-layered sucrose solution (0.85 M). The isolated cysts were then subjected to DNA extraction by four methods. To remove the artifacts, the extracted DNA were evaluated by PCR. The results of the present study showed the high level of optical density (OD) in the method I (P < 0.01) with the following steps; Giardia cysts plus crushed cover glass were vortexed. Then, the samples were boiled and then followed by freeze-thaw cycles, yet this method yielded the lowest concentration. Furthermore, the highest concentration were observed in the method II (P <0.01) with the following steps; Giardia cysts plus crushed cover glass and TAE buffer were mixed and then shaken, followed by boiling. Based on the results of the present study, using crushed cover glass, boiling and freeze-thaw cycles can be effective in destruction of G. duodenalis cyst wall and have enough efficiency for extracting DNA from G. duodenalis cysts.


Assessing the clinical utility of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus type 1 serodiscordant couples: report of 113 consecutive cycles.
To assess the utility and safety of in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) in human immunodeficiency virus-1 (HIV-1) serodiscordant couples. Retrospective study. University-based practice. HIV-1 seropositive men and seronegative women undergoing IVF-ICSI.IVF-ICSI, HIV testing of female partner and infants. IVF performance, pregnancy rates, and HIV-1 seroconversion rate. We initiated 113 IVF cycles in 61 serodiscordant couples. Due to poor ovarian response, 11.5% of cycles were canceled. The number of oocytes collected per retrieval was 17.11 +/- 9.52 (2 to 47), yielding 13.90 +/- 8.12 (1 to 42) mature oocytes suitable for ICSI, and 9.34 +/- 5.45 (0 to 24) normal fertilized oocytes. We transferred 3.54 +/- 1.09 (1 to 6) embryos. The overall clinical pregnancy rate was 44.8% per embryo transfer (ET); ongoing/delivered pregnancy rate was 36.5% per ET, with a 57.1% multiple gestation rate. Cumulatively, 50.8% of couples achieved a successful pregnancy through IVF-ICSI, 54.1% when including frozen ET cycles. There were no HIV-1 seroconversions in patients or delivered babies. HIV-1 serodiscordant couples who undergo IVF-ICSI to avoid disease transmission experience high rates of success, but also encounter complications from assisted reproductive technology similar to traditional patients. The best candidates appear to be younger women without strong risk factors for ovarian hyperstimulation syndrome.


The posterior fossa syndrome questionnaire: using science to inform practice.
Up to 34% of patients with medulloblastoma develop posterior fossa syndrome (PFS) following brain tumor resection and have increased risk of long-term neurocognitive impairments. Lack of agreement in conceptualization and diagnosis of PFS calls for improvements in diagnostic methods. The current study aimed to describe psychometric properties of a new posterior fossa syndrome questionnaire (PFSQ). The PFSQ was informed by prior research and developed by a multidisciplinary team with subject matter expertise. Participants (N = 164; 63.4% Male; 78.7% White; Mage at diagnosis = 10.38 years, SD = 5.09, range 3-31 years) included patients with newly diagnosed medulloblastoma enrolled in the SJMB12 clinical trial. Forty-four patients (26.8%) were classified as having PFS based on attending physician's post-surgical yes/no report. A PFSQ was completed by a neurologist within 2 weeks of coming to St. Jude Children's Research Hospital for adjuvant treatment, irrespective of suspicion for PFS. PFSQ items ataxia (100.00%), dysmetria (95.45%), and speech/language changes (79.55%) were most sensitive. However, ataxia (26.50%) and dysmetria (46.61%) demonstrated low specificity. Speech/language changes (81.36%), mutism (95.76%), orofacial apraxia (98.29%) and irritability (96.61%) had high specificity. A principal component analysis found four components: (1) speech/language changes, (2) apraxias (including mutism), (3) motor/oromotor, and (4) emotional lability. The PFSQ is a dimensional diagnostic approach that can be used to improve diagnostic consistency across clinical and research groups to help accelerate understanding of PFS etiology, identify surgical correlates of risk, predict long-term impairments, and develop targeted interventions. Additional measure validation, including correlation with symptom resolution, is required.


Comorbidities, risk factors and maternal/perinatal outcomes in oocyte donation pregnancies.
To evaluate pre-existing comorbidities, obstetric risk factors and adverse obstetric and neonatal outcomes in pregnancies conceived by oocyte donation, compared with naturally conceived pregnancies or by conventional IVF/intracytoplasmic sperm injection (IVF/ICSI). This retrospective single-centre contemporary cohort study reviewed data from singleton deliveries at the University Hospital of Careggi, Florence, from 2009 to 2017. Maternal and perinatal outcomes were analysed. The study included 25,851 pregnancies and newborns: 276 (1.1%) children were conceived after oocyte donation, 925 (3.6%) after IVF/ICSI and 24,650 (95.4%) after natural conception. Women in the oocyte donation group were significantly older compared with IVF/ICSI and natural conception groups (P < 0.0001) and had a higher prevalence of chronic hypertension compared with the natural conception group (P = 0.0090). They were administered anticoagulant medications more frequently during pregnancy. The incidence of gestational hypertension was significantly higher than in natural conception (aOR 3.6) and IVF/ICSI pregnancies (aOR 2.7). The incidence of Caesarean section in oocyte donation pregnancies was higher than in natural conception and IVF/ICSI groups (aOR 3.4 and 2.3, respectively). An 11-fold increased risk of post-partum haemorrhage (PPH) was found in oocyte donation versus natural conception and an almost four-fold increased risk was found in oocyte donation versus IVF/ICSI; prematurity and low birthweight were more frequent after oocyte donation versus natural conception (aOR 2.4 and 1.8, respectively). Patients undergoing oocyte donation represent a group with increased comorbidities and risk factors for adverse obstetric outcomes. Oocyte donation seems to be independently associated with gestational hypertension and PPH. Pregnancies after oocyte donation warrant clinical surveillance with proper screening and, possibly, preventive strategies.


Mutations of the MYH gene do not substantially contribute to the risk of breast cancer.
To explore whether or not there is an association between the presence of either of the germline mutations in the MutY human homologue (MYH) gene (Y165C and G382D) and the risk of breast cancer. 691 breast cancer patients and 812 healthy controls were genotyped for the MYH Y165C and G382D mutations. The frequencies of heterozygotes, homozygotes and compound heterozygotes were compared for the two groups. Four (0.6%) of 691 breast cancer cases carried a MYH Y165C mutant allele, compared to five (0.6%) of the controls (OR 1.1, 95%CI 0.29-4.0, P=0.9). Eight (1.2%) cases carried a MYH G382D mutant allele, compared to eight (1.0%) of the controls (OR 1.2, 95%CI 0.44-3.3, P=0.7). No case or control was homozygous for the variant and none were compound heterozygotes. Carriers of the MYH Y165C or G382D mutant alleles do not appear to be at increased risk for breast cancer.


Sustained Improvement in the Performance of Rapid Sequence Intubation Five Years after a Quality Improvement Initiative.
Many quality improvement interventions do not lead to sustained improvement, and the sustainability of healthcare interventions remains understudied. We conducted a time-series analysis to determine whether improvements in the safety of rapid sequence intubation (RSI) in our academic pediatric emergency department were sustained 5 years after a quality improvement initiative. There were 3 study periods: baseline (April 2009-March 2010), improvement (July 2012-December 2013), and operational (January 2014-December 2018). All patients undergoing RSI were eligible. We collected data using a structured video review. We compared key processes and outcomes with statistical process control charts. We collected data for 615 of 643 (96%) patient encounters with RSI performed: 114 baseline (12 months), 105 improvement (18 months), and 396 operational (60 months). Key characteristics were similar, including patient age. Statistical process control charts indicated sustained improvement of all 6 key processes and the primary outcome measure (oxyhemoglobin desaturation) throughout the 5-year operational period. Improvements in RSI safety were sustained 5 years after a successful improvement initiative, with further improvement seen in several key processes. Further research is needed to elucidate the factors contributing to sustainability.


Microbiota profiles in the saliva, cancerous tissues and its companion paracancerous tissues among Chinese patients with lung cancer.
Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer. Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples. Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p<0.05). A cancer-related microbiota model was constructed and produced an area under the curve of 0.74 in the training set, indicating discrimination between subjects with and without cancer. Characterization of microbiota in saliva, CT and PT from Chinese lung cancer patients revealed little difference between CT and PT, indicating that the tumor and its microenvironment might influence the local microbiome. A model to distinguish between CT and PT was constructed, which has the potential to enhance our comprehension of the involvement of microbiota in the pathogenesis of lung cancer and identify novel therapeutic targets.


Effect of Auricular Acupoint Bloodletting plus Auricular Acupressure on Sleep Quality and Neuroendocrine Level in College Students with Primary Insomnia: A Randomized Controlled Trial.
To evaluate the effects of auricular acupoint bloodletting (AB) and auricular acupressure (AA) on sleep quality and the levels of melatonin (MT), glutamic acid (Glu), and γ -aminobutyric acid (GABA) in college students with primary insomnia, and to explore the possible mechanism. Totally 74 college students at Hebei University of Chinese Medicine with primary insomnia were selected from October 2019 to October 2020. All patients were assigned to AB+AA group (37 cases, received combination of AB and AA) and AA group (37 cases, received only AA on the same acupoints) by a random number table. Each group was treated twice a week for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI) score, Chinese medicine (CM) syndrome score, total effective rate, serum concentrations of MT, Glu, and GABA, and Glu/GABA ratio were compared between the two groups after treatment and at follow-up. The safety of therapy was also evaluated. After 4-week treatment, the total scores of PSQI, each PSQI component score, and the CM syndrome scores in both groups all decreased (P<0.05); the serum MT concentrations in both groups all increased (P<0.05). The concentrations of Glu and GABA in the AB+AA group were significantly higher than those in the AA group after treatment (P<0.05). However, there was no significant difference in the ratio of Glu/GABA in both groups before and after treatment (P>0.05). At follow-up, the CM syndrome score in the AB+AA group was significantly lower than that in the AA group (P<0.05). There was no significant difference between the two groups in total effective rates and adverse events (P>0.05). Both AB+AA and AA can relieve insomnia symptoms, but a stronger long-term effect were observed for AB+AA. AB+AA can promote the secretion of MT, increase the levels of Glu and GABA more effective than AA, and regulate their imbalance, and thus it may be benificial for treating insomnia.


Comparing the effects of ankle integral and conventional physiotherapy on pain, range of motion, balance, disability, and treatment effectiveness in patients with chronic ankle instability: Randomized controlled trial.
To compare the effects of ankle integral and conventional physiotherapy on pain, range of motion, balance, disability, and treatment effectiveness in patients with chronic ankle instability (CAI). Two-arm, parallel-group, randomized, double-blind, controlled trial. 60 patients with unilateral CAI. integral physiotherapy (n = 30) or conventional physiotherapy (n = 30). Visual Analog Scale (VAS), dorsiflexion and plantarflexion range of motion, Star Excursion Balance Test (SEBT), Single Leg Hop (SLH) test, Foot and Ankle Outcome Score (FAOS), Lower Extremity Functional Score (LEFS), global rating of change, were gathered pre and post-intervention. The ANOVA results revealed statistically significant interaction for FAOS, and LEFS outcome measures (P < 0.05) and the mean change results showed there were a favorable clinical difference incline toward the integral group (meanintegral = 20.14 (14.95-25.37), meanConventional = 29.46 (24.09-34.83)). There were no interactions between group and time among other outcome measures (P > 0.05). The group main effect did not show any statistical significance (P > 0.05). Hip strengthening and balance exercises added to ankle rehabilitation could be more favorable on improving the patients' functional ability.


Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria.
Successful treatment of human tuberculosis requires 6-9 months' therapy with multiple antibiotics. Incomplete clearance of tubercle bacilli frequently results in disease relapse, presumably as a result of reactivation of persistent drug-tolerant Mycobacterium tuberculosis cells, although the nature and location of these persisters are not known. In other pathogens, antibiotic tolerance is often associated with the formation of biofilms--organized communities of surface-attached cells--but physiologically and genetically defined M. tuberculosis biofilms have not been described. Here, we show that M. tuberculosis forms biofilms with specific environmental and genetic requirements distinct from those for planktonic growth, which contain an extracellular matrix rich in free mycolic acids, and harbour an important drug-tolerant population that persist despite exposure to high levels of antibiotics.


An evaluation of changes over time in the semen parameters data used for the World Health Organization semen analysis reference ranges.
Previous meta-analyses concluded that there is a decline in sperm parameters over time. This conclusion might be incorrect due to inherent biases or focusing only on a single parameter - sperm concentration. To study trends in sperm parameters over the past 20 years using data from the trials that defined the reference ranges of the World Health Organization manual. Retrospective evaluation of the data used to define the World Health Organization reference ranges. The data from 11 studies, including 3589 participants between 1996 and 2016, were divided into three period groups based on the decade of study. Differences in semen parameters' distribution were presented in boxplot. p-values were calculated by the Kruskal-Wallis rank-sum test followed by Dunn post hoc test. Analyses were conducted using the R programming language. A small decrease was noted in mean sperm concentrations (88.1 million/ml, 87.6 million/ml, and 77.2 million/ml for the first, second, and third decades, respectively) (p < 0.01). However, the 5th percentile of sperm concentration for the third decade was higher than the first or second decades (18 million/ml versus 14.9 million/ml and 15 million/ml, respectively). No significant differences were noted in progressive motility over the years (p = 0.32). The percent of morphologically normal sperm decreased between the first (24.2%) and the second (12.6%) periods of the study (p < 0.001) and then increased in the third decade (14.2%) (p < 0.01). Total motile sperm count (TMC) declined between the second and third decades (189 million and 153.9 million, respectively, p < 0.001), at levels unlikely to decrease fertility. However, the 5th percentile of the TMC remained stable at 24.9, 20.8, and 20.6 million, for the first, second, and third decades respectively (p = 0.36). Trends in sperm parameters over the last three decades do not seem to be clinically significant.


Isolation and properties of recombinant DNA produced variants of human alpha 1-proteinase inhibitor.
Using the glyceraldehyde-3-phosphate dehydrogenase promoter, nonglycosylated human alpha 1-proteinase inhibitor, representing 10% of the soluble cell protein, has been synthesized in yeast. Two forms of this protein were isolated with one being analogous to the human plasma protein and the other having the amino acid valine replacing methionine at position 358 (the P1 position). Both proteins were more sensitive to heat inactivation than the plasma form, and both had shorter half-lives in rabbits. These differences were presumably due to the absence of carbohydrate. Each protein could bind neutrophil elastase at a rate only slightly slower than that of human plasma alpha 1-proteinase inhibitor. However, the valine variant was stable to oxidation, while the P1 methionine-containing protein was readily inactivated. The specificity of alpha 1-proteinase inhibitor (methionine) was identical to that of the plasma form; however, the valine form could only effectively bind to neutrophil or pancreatic elastase, "trypsin-like" serine proteinases not being inactivated at all. These data indicate the potential importance of mutant forms of proteinase inhibitors, produced by recombinant DNA technology, as therapeutic agents for the inactivation of excess proteinases of a specific type in tissues.


Relations of fine-root morphology on (137)Cs uptake by fourteen Brassica species.
Fourteen Brassica species consisting of seven leafy vegetables and seven root vegetables were examined for (137)Cs uptake differences in relation to their fine-root morphological characters. A pot experiment was conducted from November 2014 to February 2015 in a Phytroton using a contaminated soil of Fukushima prefecture. Leafy vegetables showed bigger root diameters, larger root surface area and larger root volume. Consequently, leafy vegetables had higher (137)Cs uptake compared to root vegetables. Among the three fine-root parameters, only root surface area was observed as a significant contributing factor to higher (137)Cs uptake in terms of transfer factor (TF, dry weight basis). Kakina exhibited higher (137)Cs TF value (0.20) followed by Chinese cabbage (0.18) and mizuna (0.17). Lower TF values were observed in turnip (0.059), rutabaga (Kitanoshou) (0.062) and radish (Ha daikon) (0.064).


Impaired contractility of left-over vein grafts used for CABG and the possible trauma caused by air exposure.
The patency of vein grafts limits the long-term results after bypass surgery. Vein graft trauma may contribute to the clinical results. Left-over pieces of vein after routine coronary bypass surgery were compared with references of the same vein that were stored with maximum care. Blood perfusion (20 h, 37 degrees C) was also tested to evaluate possible recovery. Vessel rings were measured by isometric tone recordings. Left-over veins showed a contractile dysfunction compared to reference (p < 0.01-0.001, n = 13), and that did not recover after blood perfusion. Four trauma models were tested, using saphenous vein graft (SVG)-references (n = 5). Chemical exposures (0-90 min) to NaCl-papaverin or cardioplegic medium affected the baseline (p < 0.05-0.01). With mechanical distension, up to 450 mmHg leak testing, an increased norepinephrine (NE) reactivity appeared. Air contact, 20 min, reduced the NE reactivity to half maximum (p < 0.05). Longer exposures (40-60 min) completely abolished the contractility. The saphenous vein smooth muscle function appeared permanently traumatized following routine harvesting and handling. Air exposure gave dramatic deterioration and could in theory contribute to hamper the long-term results after bypass surgery.


Executive dysfunctions among boys with Attention Deficit Hyperactivity Disorder (ADHD): performance-based test and parents report.
Difficulty in executive functions (EF) is a core symptom of ADHD. Yet, the EF assessments are still in controversy. It is still unclear whether the everyday implementation of EF can be assessed under laboratory conditions. Therefore, the purposes of the present study are: (a) to examine EF among boys with ADHD both in everyday behavior (as reported by parents) and in a performance-based test. (b) To examine correlations between the two tests. Both the Behavior Assessment of Dysexecutive Functions for Children (BADS-C) and the Behavior Rating Inventory of Executive Functions (BRIEF) were independently applied to 25 boys aged 8-11 years with ADHD and 25 age-matched typical boys. Results of the two assessments were compared between the two groups to indicate differences in EF. Correlations between the two assessments for all participants were evaluated. Overall, significant differences in EF were found between the two groups on both assessments. Significant correlations were found between BADS-C and BRIEF, specifically in metacognition but not in behavioral regulation. Findings indicate that poor EF manifests itself in everyday behavior. These difficulties are found in metacognitive and behavioral regulation components. Nevertheless, applying a valid ecological assessment of behavior regulation merits future research.


Variability of transmitter quanta released during incorporation of a false transmitter into cholinergic nerve terminals.
1. Electrophysiological techniques have been used to investigate the variability of quanta released during various stages of the incorporation of acetylmonoethylcholine (AMECh) into the transmitter store at the neuromuscular junction.2. Stimulation of the rat phrenic nerve-diaphragm preparation at 3 Hz for 15-25 min reduced the time constant of decay tau(m.e.p.c.) of miniature end-plate currents from 1.61 +/- 0.08 (mean +/- S.E. of mean) msec to 1.32 +/- 0.09 msec; this represents 45% replacement of acetylcholine (ACh) by AMECh. Total replacement of ACh was achieved by a further 30-60 min stimulation which reduced tau(m.e.p.c.) to 0.93 +/- 0.06-msec.3. At the intermediate stage of exchange, the coefficient of variation c.v.(tau) of tau(m.e.p.c.) increased from the control value of 0.094 +/- 0.005 to 0.154 +/- 0.012. The latter value was less than the value (0.29) calculated for two distinct populations of quanta (i.e. pure ACh and pure AMECh quanta). Moreover, frequency distribution histograms of tau(m.e.p.c.) did not reveal a bimodal distribution. Total replacement of ACh by AMECh achieved by the second period of stimulation decreased c.v.(tau) towards the control value.4. Pre-incubation of muscles with MECh (to replace any stored choline) or stimulation in the presence of a cholinesterase inhibitor (to prevent ACh destruction and hence re-uptake of choline) did not produce any greater degree of heterogeneity than was seen in the absence of these procedures.5. The increase in c.v.(tau) observed at the intermediate stage of replacement disappeared spontaneously with a half-time of about 1 hr at 20 degrees C.6. These results are discussed in terms of the vesicle hypothesis.


[Tumors of the gonadal stroma. Report on a Sertoli cell tumor].
A rare case of Sertoli cell tumor of the testis is described. The problems associated with this tumor type and the importance of the differential diagnosis are discussed. The clinical features of a patient with Sertoli cell tumor in a cryptorchid testis are presented. It is recognized that there is a higher incidence of tumors in undescended testis and among these are Sertoli cell tumors.


Synaptic interactions between the terminals of slow-adapting type II mechanoreceptor afferents and neurones expressing gamma-aminobutyric acid- and glycine-like immunoreactivity in the rat spinal cord.
The object of this study was to analyse the synaptic interactions of slow-adapting type II (SAII) afferent terminals in laminae III-V of the rat spinal cord. The axons of SAII afferents were physiologically characterized by intracellular recording before injection with neurobiotin and preparation for electron microscopy. Axon terminals were serially sectioned and immunolabelled with antibodies against gamma-aminobutyric acid (GABA) or glycine by using a postembedding immunogold procedure. Computer-aided reconstruction was used to reveal the relative distribution of different types of synapses on terminal and en passant synaptic boutons. Eighty-nine percent of boutons received axoaxonic synaptic contacts, the mean number of contacts per bouton being 3.5. Fifty-nine percent of presynaptic axons were immunoreactive for both GABA and glycine and 45% for GABA alone. Most boutons (95%) made axodendritic contacts, and the mean number of dendrites contacted was 1.6. More than half of the postsynaptic dendrites were greater than 1 microm in diameter. Twenty-three percent were immunoreactive for glycine, and 71% were not immunoreactive for either antibody. Synaptic triads in which an axon presynaptic to the afferent was also in contact with a dendrite postsynaptic to the afferent were seen at 63% of boutons. These results are discussed in the light of similar studies of other low-threshold mechanoreceptive afferent terminals in the rat and cat and in the context of what is known of the sensory interneurones carrying information from slow- and rapid-adapting mechanoreceptors.


A longitudinal study of age-specific reproductive output and body condition among male rhesus macaques, Macaca mulatta.
In many mammalian species, male reproductive success appears to climb sharply at young adulthood, form a brief plateau during prime ages, and decline among older animals, a pattern often attributed to reduced physical condition with ageing. However, solid evidence to either substantiate or refute this profile among nonhuman primates is lacking. Here, we combine a decade of genetic analysis of paternity among free-ranging rhesus macaques, Macaca mulatta, with information about body condition in order to evaluate how changes in morphology might govern age-specific reproduction among males. We show that age-specific reproductive success traverses the same life history profile as found in other mammals, but reductions in reproductive output with advanced age were associated with reduced chances of survivorship rather than accompanied by diminished body condition. We demonstrate that variance in male age at onset of reproduction is three times greater than variance in female age at onset of reproduction. We provide the first evidence from primates that age-specific reproductive output among males is not a consequence of age-related changes in body condition, but reflects social and demographic factors.


Improving the self-assembly of bioresponsive nanocarriers by engineering doped nanocarbons: a computational atomistic insight.
Here, molecular dynamics (MD) simulations were employed to explore the self-assembly of polymers and docetaxel (DTX) as an anticancer drug in the presence of nitrogen, phosphorous, and boron-nitrogen incorporated graphene and fullerene. The electrostatic potential and the Gibbs free energy of the self-assembled materials were used to optimize the atomic doping percentage of the N- and P-doped formulations at 10% and 50%, respectively. Poly lactic-glycolic acid (PLGA)- polyethylene glycol (PEG)-based polymeric nanoparticles were assembled in the presence of nanocarbons in the common (corresponding to the bulk environment) and interface of organic/aqueous solutions (corresponding to the microfluidic environment). Assessment of the modeling results (e.g., size, hydrophobicity, and energy) indicated that among the nanocarbons, the N-doped graphene nanosheet in the interface method created more stable polymeric nanoparticles (PNPs). Energy analysis demonstrated that doping with nanocarbons increased the electrostatic interaction energy in the self-assembly process. On the other hand, the fullerene-based nanocarbons promoted van der Waals intramolecular interactions in the PNPs. Next, the selected N-doped graphene nanosheet was utilized to prepare nanoparticles and explore the physicochemical properties of the nanosheets in the permeation of the resultant nanoparticles through cell-based lipid bilayer membranes. In agreement with the previous results, the N-graphene assisted PNP in the interface method and was translocated into and through the cell membrane with more stable interactions. In summary, the present MD simulation results demonstrated the success of 2D graphene dopants in the nucleation and growth of PLGA-based nanoparticles for improving anticancer drug delivery to cells, establishing new promising materials and a way to assess their performance that should be further studied.


Sonoanatomy of the platysmal bands: What causes the platysmal band?
The platysmal band is created by the platysma muscle, a thin superficial muscle that covers the entire neck and the lower part of the face. The platysmal band appears at the anterior and posterior borders of the muscle. To date, no definite pathophysiology has been established. Here, we observed a lack of knowledge of the anatomy of the platysma muscle using ultrasonography in this study. We conducted a descriptive, prospective study observing the platysmal band in resting and contraction states to reveal muscle changes. Twenty-four participants (aged 23-57 years) with anterior and posterior neck bands underwent ultrasonography in resting and contracted states. Ten cadavers were studied aged 67-85 years to measure the thickness of the platysma muscle at 12 points: horizontally (medial, middle, lateral) and vertically (inferior mandibular margin, hyoid bone, cricoid cartilage, superior margin of clavicle). The anterior and posterior borders of the platysma muscle were thicker than the middle of the platysma muscle when in a contracted state, and the muscle also had a convex shape when contracted. The thickness of the platysma muscle was not significantly different over 12 points in the resting state. During contraction, the platysma muscles contracted in the medial and lateral margins of the muscle, which was more significant in the posterior bands. The anterior and posterior platysmal bands are related to muscle thickness during contraction. These observations support the change in platysmal band treatment only at the anterior and posterior border of the muscle.


Comparison of types of pulmonary stenosis with the state of the ventricular septum in complete transposition of the great arteries.
The pulmonary valve and left ventricular outflow tract of 214 hearts with d-transposition of the great arteries (d-TGA) were visually inspected (126 of 214 with intact ventricular septum and 88 of 214 with ventricular septal defect [VSD]). Pulmonary stenosis (PS), either valvular, subvalvular, or in combination, was present in 26 cases and was found to be more common in the presence of a VSD (20.5%) than intact ventricular septum (6.3%). PS occurred more commonly in the presence of a supracristal VSD than an infracristal VSD (70%, 7 of 10 vs 15%, 10 of 66). Further, infracristal or supracristal VSDs were associated with different types of pulmonary obstruction. In seven of ten cases with infracristal VSD and PS, the stenosis was caused by an anomaly of an atrioventricular valve. In six of seven cases with supracristal VSD and PS, the latter was caused by membranous encirclement of the left ventricular outflow tract.


KCNQ1 and lymphovascular invasion are key features in a prognostic classifier for stage II and III colon cancer.
The risk of recurrence after resection of a stage II or III colon cancer, and therefore qualification for adjuvant chemotherapy (ACT), is traditionally based on clinicopathological parameters. However, the parameters used in clinical practice are not able to accurately identify all patients with or without minimal residual disease. Some patients considered 'low-risk' do develop recurrence (undertreatment), whilst other patients receiving ACT might not have developed recurrence at all (overtreatment). We previously analysed tumour tissue expression of 28 protein biomarkers that might improve identification of patients at risk of recurrence. In the present study we aimed to build a prognostic classifier based on these 28 biomarkers and clinicopathological parameters. Classification and regression tree (CART) analysis was used to build a prognostic classifier based on a well described cohort of 386 patients with stage II and III colon cancer. Separate classifiers were built for patients who were or were not treated with ACT. Routine clinicopathological parameters and tumour tissue immunohistochemistry data were included, available for 28 proteins previously published. Classification trees were pruned until lowest misclassification error was obtained. Survival of the identified subgroups was analysed, and robustness of the selected CART variables was assessed by random forest analysis (1000 trees). In patients not treated with ACT, prognosis was estimated best based on expression of KCNQ1. Poor disease-free survival (DFS) was observed in those with loss of expression of KCNQ1 (HR = 3.38 (95% CI 2.12 - 5.40); p < 0.001). In patients treated with ACT, key prognostic factors were lymphovascular invasion (LVI) and expression of KCNQ1. Patients with LVI showed poorest DFS, whilst patients without LVI and high expression of KCNQ1 showed most favourable survival (HR = 7.50 (95% CI 3.57-15.74); p < 0.001). Patients without LVI and loss of expression of KCNQ1 had intermediate survival (HR = 3.91 (95% CI 1.76 - 8.72); p = 0.001). KCNQ1 and LVI were identified as key features in prognostic classifiers for disease-free survival in stage II and III colon cancer patients.


Nitric oxide reduces NADPH oxidase 5 (Nox5) activity by reversible S-nitrosylation.
The NADPH oxidases (Noxs) are a family of transmembrane oxidoreductases that produce superoxide and other reactive oxygen species (ROS). Nox5 was the last of the conventional Nox isoforms to be identified and is a calcium-dependent enzyme that does not depend on accessory subunits for activation. Recently, Nox5 was shown to be expressed in human blood vessels and therefore the goal of this study was to determine whether nitric oxide (NO) can modulate Nox5 activity. Endogenously produced NO potently inhibited basal and stimulated Nox5 activity and this inhibition was reversible with chronic, but not acute, exposure to L-NAME. Nox5 activity was reduced by NO donors, iNOS, and eNOS and in endothelial cells and LPS-stimulated smooth muscle cells in a manner dependent on NO concentration. ROS production was diminished by NO in an isolated enzyme activity assay replete with surplus calcium and NADPH. There was no evidence for NO-dependent changes in tyrosine nitration, glutathiolation, or phosphorylation of Nox5. In contrast, there was evidence for the increased nitrosylation of Nox5 as determined by the biotin-switch assay and mass spectrometry. Four S-nitrosylation sites were identified and of these, mutation of C694 dramatically lowered Nox5 activity, NO sensitivity, and biotin labeling. Furthermore, coexpression of the denitrosylation enzymes thioredoxin 1 and GSNO reductase prevented NO-dependent inhibition of Nox5. The potency of NO against other Nox enzymes was in the order Nox1 ≥ Nox3 > Nox5 > Nox2, whereas Nox4 was refractory. Collectively, these results suggest that endogenously produced NO can directly S-nitrosylate and inhibit the activity of Nox5.


Glass recovery and production of manufactured aggregate from MSWI bottom ashes from fluidized bed and grate incineration by means of enhanced treatment.
Enhanced treatment of incineration bottom ashes (IBA) from municipal solid waste incineration can contribute to a circular economy since not only metals can be recovered but also glass for recycling. Moreover, the remaining mineral fraction can be utilized in concrete as manufactured aggregate. To evaluate the effects of an enhanced treatment, three IBAs from fluidized bed combustion (FB-IBAs) and three grate incineration bottom ashes (G-IBAs) were standardly treated in a jig and further processed on a pilot scale, including improved metal recovery and sensor-based glass separation. The removed glass fractions were weighed and their composition was assessed by means of manual sorting. The manufactured aggregate was also sorted manually and its total and leachate contents were determined before and after aging. Results showed general differences between FB-IBAs and G-IBAs. For G-IBAs, higher contents of heavy metals and residual metal pieces were determined, while the share of glass removed was low compared to FB-IBA. The treated mineral fractions from G-IBA contained more mineral agglomerates, whereas FB-IBAs contained more glass. However, the glass-fractions removed from FB-IBAs need further treatment to be accepted in glass recycling. Austrian limit values for utilization in concrete were met by all manufactured aggregates produced from FB-IBA, but only by one from G-IBA. Overall, the enhanced treatment in the study performed well compared to the literature. Nevertheless, further investigations are necessary to improve the recyclability of the recovered glass fractions and to determine the technical suitability of manufactured aggregates produced from IBAs.


Efficacy of Intra-articular Triamcinolone and Hyaluronic Acid in a Frozen Shoulder Rat Model.
Intra-articular corticosteroid or hyaluronic acid (HA) is commonly prescribed for frozen shoulder. However, few studies have investigated histological and molecular changes after injection. To compare the effectiveness of intra-articular injections of triamcinolone and HA in a frozen shoulder rat model and verify a greater effect of triamcinolone in passive shoulder abduction compared with HA. Controlled laboratory study. Twenty male Sprague-Dawley rats were randomly allocated into 4 groups (n = 5 in each): control group, which did not receive cast immobilization or injection, and 3 experimental groups, which received 3 weeks of unilateral shoulder immobilization followed by intra-articular injections (normal saline, triamcinolone, or HA) at the immobilized shoulder. Passive shoulder abduction angle, histological and immunohistochemical staining, and Western blotting results were assessed 2 weeks after injection. The intensity and extent of staining were converted to semiquantitative scores for further analysis. Shoulder abduction angles before sacrifice were 153.0°± 2.7° (control group), 107.0°± 5.7° (saline group), 139.0°± 9.6° (triamcinoline group), and 110.0°± 10.6° (HA group), showing significant differences between control and saline groups, control and HA groups, saline and triamcinoline groups, and triamcinoline and HA groups (P < .001) but not between control and triamcinoline groups (P = .053). Histologic evaluation revealed an increase in synovial folds and thickening of the capsular membrane in the saline and HA groups; this change was not evident in the triamcinolone group. A comparison of semiquantitative scores revealed greater expression levels of proteins involved in fibrosis and angiogenesis in the saline and HA groups compared with the control and triamcinolone groups. In Western blotting, the expression of inflammatory cytokines and the receptor for advanced glycation end products was significantly lower in the triamcinolone and HA groups than in the saline group. Triamcinolone injection was more effective than normal saline or HA injection in improving range of motion and reversing fibrotic and angiogenic features of frozen shoulder. Both triamcinolone and HA injections elicited anti-inflammatory effects. The antifibrotic and antiangiogenic properties of triamcinolone and the anti-inflammatory properties of both triamcinolone and HA should be considered when performing injections in clinical settings.


The effectiveness of low-level laser therapy as an adjunct to non-surgical periodontal treatment: a meta-analysis.
Although low-level laser therapy (LLLT) has been demonstrated to have a biomodulatory effect on periodontal tissue, no systematic review has exclusively addressed its effectiveness as an adjunct to non-surgical periodontal treatment. This study aimed to evaluate whether an additional benefit exists for the application of LLLT compared with scaling and root planing (SRP) alone. An extensive search was conducted in the Cochrane Library (Issue 8, 2015), PubMed (1997) and EMBASE (1947) before August 2015 for randomized controlled trials (RCTs). The bias risk was assessed with the Cochrane tool for risk of bias evaluation. A meta-analysis was performed using REVMAN 5.3. After independent screening of 354 initial records, eight publications (seven RCTs) were included. However, six were rated as 'having a high risk of bias' as a result of major methodological weakness in 'allocation concealment' and 'blinding of key personnel'. Meta-analysis showed that LLLT-mediated SRP demonstrated significant short-term benefits over SRP monotherapy in the improvement of the probing pocket depth (p = 0.0009 at 1 mo; p = 0.03 at 2 mo) and the level of interleukin-1β in the gingival crevicular fluid (p = 0.01 at 1 mo). Nevertheless, LLLT failed to show significant additional intermediate-term (3 and 6 mo) effects in terms of clinical parameters and alveolar bone density. These findings indicated that LLLT showed only short-term additional benefits after conventional SRP. Its long-term effects remain unclear due to substantial methodological weaknesses and an insufficient number of current studies. Future RCTs with better designs and longer follow-up periods are required to assess the effectiveness of LLLT as an adjunctive treatment strategy in patients with periodontal disease.


Separation of keratinocytes by density gradient centrifugation for DNA cytofluorometry.
A method for the separation of guinea pig epidermal keratinocytes, in which the Feulgen-stainable material suffers minimal damage, has been investigated. The principal stage involves trypsin treatment of the epidermal sheet, stripped from the dermis with ethylenediamine tetraacetic acid. The epidermal cells thus isolated are separated into three groups by centrifugation on a continuous colloidal silica (Percoll) density gradient. The resulting arrangement of the keratinocytes in the centrifuge tube corresponds to their arrangement in situ, with basal cells at the bottom and the more differentiated cells above. By morphological examination, it can be shown that relatively pure fractions of basal cells, spinous cells, and granular cells are obtained by this method. With respect to DNA distribution pattern, there was good agreement between that of keratinocytes separated by the microdissection-ultrasonic irradiation method, or by the chymotrypsin method as reported previously by us, and that obtained by the present method.


The association of changes in body mass index and metabolic parameters between adults with overweight or obesity and their children in a family-based randomized trial (DiOGenes).
Family-based approaches have been reported to be effective in improving overweight or obesity in children. To investigate the relationship of changes in body mass index and metabolic parameters between adults with overweight or obesity and their children during a weight-maintenance family-based dietary intervention. In a multicentre randomized controlled trial, families with at least one parent with overweight or obesity and one healthy child aged between 5 and 18 years, of which the parents completed an 8-week weight-loss phase successfully, were randomized into five different dietary intervention groups to achieve weight maintenance for 6 months. Anthropometric parameters and body composition were measured and blood samples were collected before and after the dietary intervention. Data were analysed using Pearson correlation coefficient analyses and multiple linear regression analysis adjusted for diet group, centre, child's sex and age. A positive association was found between the change in body mass index (BMI) of the mother and change in BMI-for-age Z-score of first and second child (std β = 0.248, p = 0.000; std β = 0.326, p = 0.000, respectively). The change in BMI of the father was only significantly associated with the change in BMI-for-age Z-score of first child (std β = 0.186, p = 0.031). No consistent pattern of associations between parents and children was found for homeostatic model assessment for insulin resistance, fasting glucose and fasting insulin. This study supports the inclusion of parents into family-based dietary approaches for weight management of their children regardless of the child's weight status in eight different countries throughout Europe.


A High-Voltage and High-Capacity Li1+x Ni0.5 Mn1.5 O4 Cathode Material: From Synthesis to Full Lithium-Ion Cells.
We report Co-free, Li-rich Li1+x Ni0.5 Mn1.5 O4 (0<x<1) compounds as high-voltage and high-capacity cathode materials for Li-ion cells. Their tailored morphology allows high density and facile processability for electrode development. In the potential range 2.4-4.9 V, the cathode material of composition Li1.5 Ni0.5 Mn1.5 O4 shows excellent performance in terms of capacity and cycling stability in half-cells. In addition, for the first time, we demonstrate the application of the high-voltage and high-capacity cathode in full Li-ion cells with graphite anodes with very high cycling stability. The electrochemical performance and low cost of the cathode material, together with the feasibility of a chemical method to obtain Li-rich Li1+x Ni0.5 Mn1.5 O4 (0<x<1), make practical applications of high-energy density Li-ion batteries possible.


Current Techniques in Scapholunate Ligament Reconstruction.
Scapholunate ligament injuries are common and can lead to a predictable pattern of arthritis (scaphoid lunate advanced collapse wrist) if unrecognized or untreated. This article describes the relevant anatomy, biomechanics, and classification system, and provides an up-to-date literature-based review of treatment options, including acute repair and various reconstruction techniques. It also helps guide surgeons in making decisions regarding a systematic treatment algorithm for these injuries.


Implementing a resilience coach program to support first year housestaff during the COVID-19 pandemic: early pilot results and comparison with non-housestaff sessions.
In response to the COVID-19 pandemic, we launched the Penn Medicine Coping First Aid program to provide psychosocial supports to our health system community. Our approach leveraged lay health worker volunteers trained in principles of Psychological First Aid to deliver coaching services through a centralized virtual platform. We emailed all (n = 408) first year housestaff (i.e., residents and fellows) with an invitation to schedule a session with a resilience coach. We compared the mental health concerns, symptoms, and Psychological First Aid techniques recorded in (n = 67) first year housestaff sessions with (n = 91) sessions of other employees in the health system. Between June and November 2020, forty-six first year housestaff attended at least one resilience coaching session. First year housestaff most commonly presented with feelings of anxiety and sadness and shared concerns related to the availability of social support. Resilience coaches most frequently provided practical assistance and ensured safety and comfort to first year housestaff. First year housestaff reported fewer physical or mental health symptoms and held shorter sessions with resilience coaches than non-housestaff. This work offers insights on how to address psychosocial functioning through low-intensity interventions delivered by lay personnel. More research is needed to understand the efficacy of this program and how best to engage housestaff in wellness and resilience programs throughout training, both during and beyond COVID-19.


Prey capture by three Pinguicula species in a subarctic environment.
The number and biomass of prey captured were estimated for Pinguicula alpina, P. villosa and P. vulgaris in a subarctic environment. Seasonal captures were estimated for one site per species for 4-5 years. Captures were related to reproductive status (reproductive/non-reproductive) and to leaf area. For one species (P. vulgaris) the catch was also compared across a range of habitats. Of the seasonal catch, 50-75% was obtained during June and less than 5% during August. For P. alpina and P. villosa the seasonal catch varied threefold or more between years (means of 89-329 μg dry matter plant-1 season-1 for P. alpina, and 11-91 μg dry matter plant-1 season-1 for P. villosa), whereas the between-year variation for P. vulgaris was small (mean c. 600 μg plant-1 season-1). Large variations were, however, observed among habitats for P. vulgaris. Captured prey may contribute a substantial amount of nutrients to the most successful individuals (up to 85% of the mean seasonal turnover), but prey capture varied greatly and during any given season many individuals obtained only marginal amounts of nutrients through carnivory. P. vulgaris trapped almost twice as much per unit leaf area and season as the other two species (224 for P. vulgaris versus 127 μg cm-2 season-1 for the other two species). Reproductive individuals of P. vulgaris trapped almost twice as much as non-reproductive individuals (after taking differences in leaf area into account). For the other two species no differences were observed between reproductive and non-reproductive individuals.


Nurse-based evaluation of point-of-care assays for glycated haemoglobin.
Various devices are now available to measure glycated haemoglobin (HbA1c) outside of the laboratory. The aim of this study was to assess the performance of these point-of-care instruments in the hands of non-laboratory trained personnel. Two nursing staff tested samples from patients attending a diabetes research clinic using the following point-of-care devices for HbA1c-Metrica A1C Now, Bayer DCA 2000, Cholestech GDX and Axis-Shield Nycocard HbA1c. In addition they performed regular analysis of quality control samples. The effects on analytical performance of multiple operators as well as laboratory-trained staff, were also assessed. All measurements were compared to a boronate-affinity HPLC method in the central laboratory. The mean HbA1c difference of the point-of-care devices compared to the laboratory reference method ranged from -0.31% to +0.39%. Only the DCA device had a between batch imprecision of less than 5%. The analytical performance obtained by laboratory staff was similar to nursing staff for 3 devices and better for the Nycocard device. On the basis of the results obtained by nursing staff, only the DCA of the devices tested, can be recommended for measurement of HbA1c outside of the laboratory.


Commercially acquired açaí pulps contamination by Trypanosoma cruzi.
The etiological agent of Chagas disease is the protozoan Trypanosoma cruzi. According to the World Health Organization, about seven to eight million people are infected with T. cruzi worldwide. The main routes of transmission are vectorial and oral, which has assumed great epidemiological importance, since there is no legislation that requires the pasteurization of açaí pulp. The present work aimed to look T. cruzi in 35 samples of açaí ice cream sold at different points of sale, covering 11 different cities in São Paulo State. Thus, the parasitological technique of forced sieving and the molecular test of Polymerase Chain Reaction were performed. For PCR analysis were used the 121/122 primer that amplifies the kinetoplast of the T. cruzi DNA (kDNA). By the forced sieving technique, the açaí pulp aliquots were analyzed under different storage temperatures and in different periods. One positive sample (2.86%) were observed at six hours at room temperature, but without motility and negative to the PCR technique. Two other açaí samples (5.71%) were positive by PCR, but negative by forced sieving. The results indicate the need for quality control and good manufacturing practices for the safe consumption of açaí-derived products.


Disruption of a stapled anastomosis following therapeutic ultrasonics--is there a risk? Report of a case.
We examined the theoretic possibility that therapeutic ultrasound can disrupt a stapled gastrointestinal anastomosis. A case is reported in which leakage of a stapled ileocolic anastomosis occurred following therapeutic ultrasound. Calculations are performed on the power of the ultrasound beam and its adsorption and dispersion in the tissue between the probe and anastomosis to establish its intensity at the anastomosis. Ultrasound intensity at the anastomosis in this patient was calculated at 10 to 46 mW/cm2. Although the calculated ultrasound intensities at the anastomosis do not appear to be very high, other factors such as "pressure doubling" and "stress concentration" at the stapled surface suggest that therapeutic ultrasound may cause staple disruption.


MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer.
Tumor-suppressor Pdcd4 inhibits transformation and invasion and is downregulated in cancers. So far, it has not been studied as to whether miRNAs, suppressing target expression by binding to the 3'-UTR, regulate Pdcd4 or invasion. The present study was conducted to investigate the regulation of Pdcd4, and invasion/intra-vasation, by miRNAs. A bioinformatics search revealed a conserved target-site for miR-21 within the Pdcd4-3'-UTR at 228-249 nt. In 10 colorectal cell lines, an inverse correlation of miR-21 and Pdcd4-protein was observed. Transfection of Colo206f-cells with miR-21 significantly suppressed a luciferase-reporter containing the Pdcd4-3'-UTR, whereas transfection of RKO with anti-miR-21 increased activity of this construct. This was abolished when a construct mutated at the miR-21/nt228-249 target site was used instead. Anti-miR-21-transfected RKO cells showed an increase of Pdcd4-protein and reduced invasion. Moreover, these cells showed reduced intra-vasation and lung metastasis in a chicken-embryo-metastasis assay. In contrast, overexpression of miR-21 in Colo206f significantly reduced Pdcd4-protein amounts and increased invasion, while Pdcd4-mRNA was unaltered. Resected normal/tumor tissues of 22 colorectal cancer patients demonstrated an inverse correlation between miR-21 and Pdcd4-protein. This is the first study to show that Pdcd4 is negatively regulated by miR-21. Furthermore, it is the first report to demonstrate that miR-21 induces invasion/intravasation/metastasis.


Concentration- and time-dependent genotoxicity profiles of isoprene monoepoxides and diepoxide, and the cross-linking potential of isoprene diepoxide in cells.
Isoprene, a possible carcinogen, is a petrochemical and a natural product being primarily produced by plants. It is biotransformed to 2-ethenyl-2-methyloxirane (IP-1,2-O) and 2-(1-methylethenyl)oxirane (IP-3,4-O), both of which can be further metabolized to 2-methyl-2,2'-bioxirane (MBO). MBO is mutagenic, but IP-1,2-O and IP-3,4-O are not. While IP-1,2-O has been reported being genotoxic, the genotoxicity of IP-3,4-O and MBO, and the cross-linking potential of MBO have not been examined. In the present study, we used the comet assay to investigate the concentration- and time-dependent genotoxicity profiles of the three metabolites and the cross-linking potential of MBO in human hepatocyte L02 cells. For the incubation time of 1 h, all metabolites showed positive concentration-dependent profiles with a potency rank order of IP-3,4-O > MBO > IP-1,2-O. In human hepatocellular carcinoma (HepG2) and human leukemia (HL60) cells, IP-3,4-O was still more potent in inducing DNA breaks than MBO at high concentrations (>200 μM), although at low concentrations (≤200 μM) IP-3,4-O exhibited slightly lower or similar potency to MBO. Interestingly, their time-dependent genotoxicity profiles (0.5-4 h) in L02 cells were different from each other: IP-1,2-O and MBO (200 μM) exhibited negative and positive profiles, respectively, with IP-3,4-O lying in between, namely, IP-3,4-O-caused DNA breaks did not change over the exposure time. Further experiments demonstrated that hydrolysis of IP-1,2-O contributed to the negative profile and MBO induced cross-links at high concentrations and long incubation times. Collectively, the results suggested that IP-3,4-O might play a significant role in the toxicity of isoprene.


miR-363 induces transdifferentiation of human kidney tubular cells to mesenchymal phenotype.
microRNAs (miRNAs) are non-coding small RNAs that regulate embryonic development, cell differentiation and pathological processes via interaction with mRNA. Epithelial-mesenchymal transition (EMT) is pathological process that involves in a variety of diseases such as cancer or fibrosis. In this study, we identified miR-363 as a potent inducer of EMT by microarray analysis in human kidney tubular cells, and analyzed the function and mechanisms of miR-363. Overexpression of miR-363 induced mesenchymal phenotypes with loss of epithelial phenotypes in human kidney tubular cells. In addition, in vitro scratch assay demonstrated that miR-363 promotes cell migration of primary culture of human kidney tubular cells. We identified TWIST/canonical WNT pathway as the downstream effecter of miR-363, and inhibition of canonical WNT by small molecule, IWR-1, attenuated EMT induced by miR-363. miR-363 induces transdifferentiation of human kidney tubular cells via upregulation of TWIST/canonical WNT pathway.