Release of oral submucous fibrosis and reconstruction using superficial temporal fascia flap and split skin graft--a new technique.
Long standing oral submucous fibrosis is associated with involvement of the oral submucosa and the muscles of mastication leading to difficulty in mouth opening. Various surgical modalities are mentioned for release but each has its own limitations. This article introduces a new technique of release of submucous fibrosis and reconstruction using superficial temporal fascia flap and split skin graft. The surgical technique involves a pre-auricular incision extending into the temporal region with dissection carried out in the sub follicular plane to develop the superficial temporal fascia flap to its maximum extent. The masseter muscle origin is released from the zygomatic arch and the temporalis muscle insertion is released from the coronoid process through an external approach. The entire fibrosed mucosa is released intraorally to create a mucomuscular defect thus achieving full mouth opening. The superficial temporal fascia flap is then brought in and sutured to the intraoral defect, which is then covered with a split thickness skin graft. This procedure is performed bilaterally. A total of five patients were treated with this new technique and all of them showed good mouth opening in long term follow up. There was no donor site morbidity. The incision line is well hidden in the hair bearing area. A well vascularised superficial temporal fascia flap brings in good blood supply to the area of affected muscle and mucosa to improve its function.


Modulation of locomotor activity by substance P in rats.
The effects of intraperitoneally or intracerebrally (DA A-10 area) administered substance P (SP) on locomotor activity of rats were studied in an exact 12-h light/12-h dark cycle changing from dark to light at 6 a.m. SP was administered either at 11 a.m. (light phase, minimal locomotor activity) or at 7 p.m. (dark phase, maximal locomotor activity). The effects of 12.5 micrograms/kg SP intracerebral and 125 micrograms/kg SP intraperitoneal were very similar. In the light phase SP produces excitation but inhibition of locomotion in darkness. Hence, the effect of SP depends on the internal mechanisms controlling motor activity and tends to level off the spontaneous circadian oscillation. We found a long lasting SP effect during both the light and dark period. The present experiments led us to the conclusion that SP has a levelling effect on locomotor activity. Probably this effect might be explained as SP's action on the dopaminergic pathway or dopamine metabolism, because the dopamine content in neurons also has a circadian rhythm.


Comparison of cefazedone with cefazolin and cephalothin in treatment of experimental infections in mice.
The chemotherapeutic efficacy of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) was assayed in comparison to cefazolin and cephalothin in experimental bacterial murine infections with 6 gram-positive and 8 gram-negative strains of the genera Staphylococcus, Streptococcus, Pneumococcus, Escherichia, Klebsiella, Proteus, Pasteurella and Salmonella. In 5 out of 14 strains (Staphylococci, Streptococci, E. coli, Klebsiella) cefazedone was markedly superior to cefazolin, whereas both compounds were of similar activity against the remaining 9 isolates. As compared to cephalothin, cefazedone exhibited highly superior effectiveness in all organisms tested.


Critical evaluation of soil contamination assessment methods for trace metals.
Correctly distinguishing between natural and anthropogenic trace metal contents in soils is crucial for assessing soil contamination. A series of assessment methods is critically outlined. All methods rely on assumptions of reference values for natural content. According to the adopted reference values, which are based on various statistical and geochemical procedures, there is a considerable range and discrepancy in the assessed soil contamination results as shown by the five methods applied to three weakly contaminated sites. This is a serious indication of their high methodological specificity and bias. No method with off-site reference values could identify any soil contamination in the investigated trace metals (Pb, Cu, Zn, Cd, Ni), while the specific and sensitive on-site reference methods did so for some sites. Soil profile balances are considered to produce the most plausible site-specific results, provided the numerous assumptions are realistic and the required data reliable. This highlights the dilemma between model and data uncertainty. Data uncertainty, however, is a neglected issue in soil contamination assessment so far. And the model uncertainty depends much on the site-specific realistic assumptions of pristine natural trace metal contents. Hence, the appropriate assessment of soil contamination is a subtle optimization exercise of model versus data uncertainty and specification versus generalization. There is no general and accurate reference method and soil contamination assessment is still rather fuzzy, with negative implications for the reliability of subsequent risk assessments.


Pathogenesis of feline panleukopenia virus and canine parvovirus.
Feline panleukopenia virus (FPV) and canine parvovirus (CPV) are autonomous parvoviruses which infect cats or dogs, respectively. Both viruses cause an acute disease, with virus replicating for less than seven days before being cleared by the developing immune responses. The viruses have a broad tropism for mitotically active cells. In neonatal animals the viruses replicate in a large number of tissues, and FPV infection of the germinal epithelium of the cerebellum leads to cerebellar hypoplasia, while CPV may infect the hearts of neonatal pups, causing myocarditis. In older animals the virus replicates systemically, primarily in the primary and secondary lymphoid tissues, and also in the rapidly replicating cells of the small intestinal epithelial crypts. A transient panleukopenia or relative lymphopenia is often observed after FPV or CPV infection, respectively. Whether the reduction in cell numbers in vivo is due to virus replicating in and killing cells, or due to other indirect effects, is not known. However, FPV kills both erythroid and myeloid colony progenitors in in vitro bone marrow cultures, and it has been suggested that virus replication in the myeloid cells in vivo could lead to the reduced neutrophil levels seen after FPV infection of cats.


Impairment of the humoral and CD4(+) T cell responses in HTLV-1-infected individuals immunized with tetanus toxoid.
T cells from HTLV-1-infected individuals have a decreased ability to proliferate after stimulation with recall antigens. This abnormality may be due to the production of regulatory cytokine or a dysfunctional antigen presentation. The aims of this study were to evaluate the antibody production and cytokine expression by lymphocytes before and after immunization with tetanus toxoid (TT) and to evaluate the immune response of monocytes after stimulation with TT and frequency of dendritic cells (DC) subsets. HTLV-1 carriers (HC) and uninfected controls (UC) with negative serology for TT were immunized with TT, and the antibody titers were determined by ELISA as well as the cell activation markers expression by monocytes. The frequencies of DC subsets were determined by flow cytometry. Following immunization, the IgG anti-TT titers and the frequency of CD4(+) T cells expressing IFN-γ, TNF-α and IL-10 in response to TT were lower in the HC than in the UC. Additionally, monocytes from HC did not exhibit increased HLA-DR expression after stimulation with TT, and presented low numbers of DC subsets, therefore, it's necessary to perform functional studies with antigen-presenting cells. Collectively, our finding suggests that HC present an impairment of the humoral and CD4(+) T cell immune responses after vaccination.


Lens thickness of Indian eyes: impact of isolated lens opacity, age, axial length, and influence on anterior chamber depth.
To report relationship of age group and axial length (AL) category to lens thickness values in eyes with a clear lens or different types of isolated cataract (nuclear, cortical, and posterior subcapsular (PSC)). Further, we evaluated lens thickness values on anterior chamber depth (ACD) in these eyes. Observational clinic-based study.MethodsAn observational study of 1442 eyes of 1442 individuals (816 eyes with isolated cataract and 626 eyes with clear lens) of those above 25 years of age was evaluated. AL and lens thickness were performed with an A-scan ultrasound after dilatation of the pupil, and manual optical pachymetry was used to measure ACD after dilatation of the pupil. Lens thickness. Multiple regression analysis revealed that with each decade of advancement in age, the lens thickness increased by 0.155 mm (P<0.001). The difference in lens thickness after adjusting for age group and AL category was less in cortical cataract by -0.25 mm (P<0.001) and PSC by -0.29 mm (P<0.001); With advancement in AL category, lens thickness decreased by 0.004 mm (P<0.001). After adjusting for all the parameters/variables, regression analysis revealed that as lens thickness increased, there was a significant decrease in ACD (mean -0.44 mm; P<0.001). Lens thickness was significantly greater in clear lenses when compared with isolated cataracts-greatest with nuclear cataract and least with PSC. Age group and AL category had a significant impact on the lens thickness of both cataract and clear lens. A significant decrease in ACD was found with the increase in lens thickness.


Double inter-atrial septum: a rare cause of cardioembolic stroke.
Double inter-atrial septum is an exceedingly rare congenital cardiac abnormality. We describe a case of transient ischaemic attack in a 53 year-old female found to have double inter-atrial septa on transthoracic and transoesophageal echocardiography. The midline inter-atrial chamber enclosed by the two septa was found to be continuous with the left atrium, with stasis in this accessory chamber predisposing to thrombus formation and cardio-embolic events. The case highlights the importance of transoesophageal echocardiography in the investigation of stroke, particularly in younger individuals.


Fetus in fetu from newborn's mediastinum: case report and a review of literature.
Fetus in fetu is a rare congenital anomaly, when the malformed monozygotic twin is found within the body of a living child or sometimes in an adult. We report a case of fetus in fetu diagnosed during the early third trimester of pregnancy, in the medial and inferior portions of anterior mediastinum of the dominant twin. The diagnosis was suspected by prenatal ultrasound and fetal magnetic resonance imaging. It was postnatally confirmed by CT and RTG, surgically removed after birth and histologically examined. Histologically we found well-developed organs and tissues derived from all germ layers. To our knowledge, we describe the fourth case of fetus in fetu located in the thorax, and the second case located in the anterior mediastinum. This case highlights the usefulness of prenatal ultrasound and MRI in the diagnosis of mediastinal masses, and the usefulness of complete histological examination for confirmation of diagnosis of fetus in fetu. We also reviewed the possible embryologic backgrounds of this congenital anomaly.


Experimental model of dissecting aneurysms.
The pathogenesis and optimal treatment for arterial dissection are still unclear. We devised an experimental model of arterial dissection and observed the morphologic changes with angiography. Sixty-four experimental dissections were created in the common carotid arteries of 34 mongrel dogs. After a small incision was made in the arterial adventitia, it was dissected from the media. Elliptical defects (2, 4, 6, and 8 mm in groups I-A, I-B, I-C, and I-D, respectively; n = 47) or longitudinal incisions (4, 6, and 8 mm in groups II-A, II-B, and II-C, respectively; n = 17) were made in the intima distal to the adventitial incision to serve as an entry zone for dissection. Immediately after the lesions were created, the influx of blood into the dissected cavity produced massive subadventitial hematomas, resulting in stenotic changes in all of the arteries, including seven with occlusion. Follow-up (1-week) angiograms demonstrated complete healing, with normal arterial calibers in 11 (79%) of 14 I-A lesions and aneurysm formation in nine (69%) of 13 I-B lesions. All 10 I-D lesions had complete arterial occlusion. Persistent stenosis was observed in all 10 I-C lesions; six of these developed aneurysms. Pathologic examination of the freshly dissected cavities revealed a clot-filled cleft between the media and adventitia. Mature aneurysms, evaluated 3 mo later, had endothelialization within the aneurysmal dome. Morphologic changes after arterial dissection are closely related to the size of the intimal entry zone, which may determine whether a dissecting aneurysm forms.


Biochemical, hydrological and mechanical behaviors of high food waste content MSW landfill: Preliminary findings from a large-scale experiment.
A large-scale bioreactor experiment lasting for 2years was presented in this paper to investigate the biochemical, hydrological and mechanical behaviors of high food waste content (HFWC) MSW. The experimental cell was 5m in length, 5m in width and 7.5m in depth, filled with unprocessed HFWC-MSWs of 91.3 tons. In the experiment, a surcharge loading of 33.4kPa was applied on waste surface, mature leachate refilling and warm leachate recirculation were performed to improve the degradation process. In this paper, the measurements of leachate quantity, leachate level, leachate biochemistry, gas composition, waste temperature, earth pressure and waste settlement were presented, and the following observations were made: (1) 26.8m3 leachate collected from the 91.3 tons HFWC-MSW within the first two months, being 96% of the total amount collected in one year. (2) The leachate level was 88% of the waste thickness after waste filling in a close system, and reached to over 100% after a surcharge loading of 33.4kPa. (3) The self-weight effective stress of waste was observed to be close to zero under the condition of high leachate mound. Leachate drawdown led to a gain of self-weight effective stress. (4) A rapid development of waste settlement took place within the first two months, with compression strains of 0.38-0.47, being over 95% of the strain recorded in one year. The compression strain tended to increase linearly with an increase of leachate draining rate during that two months.


Perceiving mental states.
This paper argues that our awareness of the mental states of other agents is often perceptual in character. It draws partly on recent experimental findings concerning perception of animacy and intentionality. But it also emphasizes the unencapsulated nature of perception generally, and argues that concepts (including mental-state concepts) can be bound into the contents of conscious perception. One of the main arguments used in support of this conclusion draws on recent work concerning the nature and contents of working memory.


Teratogenicity and placental transfer of all-trans-, 13-cis-, 4-oxo-all-trans-, and 4-oxo-13-cis-retinoic acid after administration of a low oral dose during organogenesis in mice.
13-cis-Retinoic acid (isotretinoin) is teratogenic in humans at therapeutic doses (0.5-1.5 mg/kg) but only marginally teratogenic in the mouse at a high dose of 100 mg/kg. Previous results explained why the cis isomer of retinoic acid was much less teratogenic than the trans isomer in mice. It was found that the placental transfer of all-trans retinoic acid to the mouse embryo was far greater than that of the 13-cis isomer. Since our previous study had been performed with exceedingly high doses (100 mg/kg) of 13-cis-retinoic acid and all-trans-retinoic acid, we have now performed additional experiments with 10-fold lower doses. Studies were also done with the main metabolites of the two retinoids (the 4-oxo-derivatives) to elucidate the metabolism, pharmacokinetics, and teratogenicity of each single compound. It was shown that all-trans-retinoic acid and 4-oxo-all-trans-retinoic acid were extremely teratogenic, whereas their corresponding cis isomers caused only 2% cleft palate. Embryonic exposure to the trans isomers was likewise higher than that to the cis isomers, as shown by the far higher embryonic peak concentrations and by the 30-fold higher areas under the concentration-time curve values reached for the trans isomers compared with the cis isomers. At 8 hr, embryo/maternal plasma ratios were higher than 1 after administration of the all-trans compounds. Concentrations found in the placenta and yolk sac were higher for the trans forms than for the cis forms. We propose a model for a facilitated transport of the all-trans forms to the developing embryo and suggest that the conversion to the trans isomer and trans metabolite could play a major role in the teratogenicity of 13-cis-retinoic acid in humans.


Contamination of peripheral blood by monoclonal B cells following treatment of multiple myeloma by high-dose chemotherapy.
Peripheral blood samples obtained from five patients with multiple myeloma, after high-dose chemotherapy, were studied for monoclonal B plasma cell contamination. We used the technique of immunoglobulin heavy chain gene 'fingerprinting' at the time of diagnosis and during apheresis. The level of sensitivity of this technique is between 0.01% and 0.001% in two patients in whom a monoclonal population was detected in peripheral blood.


Increased incidence of coronary heart disease associated with "double burden" in a cohort of Italian women.
Objective of this study was to assess the risk of coronary heart disease (CHD) associated with the combination of employment status and child care among women of working age, also examining the sex of the offspring. Only two previous studies investigated the effect of double burden on CHD, observing an increased risk among employed women with high domestic burden or providing child care, although the relative risks were marginally or not significant. The study population was composed of all women 25-50 years old at 2001 census, living in Turin in families composed only by individuals or couples, with or without children (N = 109,358). Subjects were followed up during 2002-2010 for CHD incidence and mortality through record-linkage of the cohort with the local archives of mortality and hospital admissions. CHD risk was estimated by multivariate Poisson regression models. Among employed women, CHD risk increased significantly by 29% for each child in the household (IRR = 1.29) and by 39% for each son (IRR = 1.39), whereas no association with the presence of children was found among non-employed women or among employed women with daughters. When categorized, the presence of two or more sons significantly increased CHD risk among employed women (IRR = 2.23), compared to those without children. The study found a significant increase in CHD risk associated with the presence of two or more sons in the household, but not daughters, among employed women. This is a new finding, which should be confirmed in other studies, conducted also in countries where the division of domestic duties between males and females is more balanced, such as the European Nordic countries.


Atmospheric particulate matters in an Indian urban area: Health implications from potentially hazardous elements, cytotoxicity, and genotoxicity studies.
The nature of the atmospheric particulate matters (PMs) varies depending on their sizes and their origin from different activities in the background environment. These PMs are associated with potentially hazardous elements (PHEs) such as organic compounds (e.g. Polyaromatic Hydrocarbons) that can be harmful to health. The main objective of this work is the identification and investigation of the toxicological aspects of PHEs in PMs during pre-monsoon and post-monsoon season in an urban area of Northeast region (NER) of India. In the course of the study, the 24 -hs average concentrations of PMs were detected to be more than two-times higher than the Indian standard limit (NAAQ, category) which indicates poor air quality in both the seasons around the sampling sites. This study demonstrates that the concentrations of PM-bound PAHs are mutagenic and that the Excess Cancer Risks exceed the USEPA standard limits. PMs cause cytotoxicity and can also induce genotoxicity to human health analyzed by cell culture and gel electrophoresis. This study helps to promote research to evaluate the PMs bound PHEs toxicity in diverse human cell lines and also their relationship with climatic factors as well as quantitative source apportionment for mitigation purposes.


Chitooligosaccharides-modified PLGA nanoparticles enhance the antitumor efficacy of AZD9291 (Osimertinib) by promoting apoptosis.
The nano drug delivery system (NDDS) has been extensively investigated for cancer treatment because of its ability to enhance drug efficacy. However, there are only a few studies attempting NDDS for AZD9291 (Osimertinib). Here, we encapsulated AZD9291 in chitooligosaccharides (COS)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles. COS, a cationic polymer, was used to develop positively charged nanoparticles with good biological affinity. The prepared AZD-PLGA-COS NPs exhibited a smaller particle size (176.6 ± 0.4 nm), a positively charged surface (+18.65 ± 0.38 mV), and an increased cellular uptake. The IC50 of H1975 cells was reduced by 45.90%, and the expression of p-EGFR, PARP, Bak, caspase-9, Bax, and Bcl-2 was regulated to promote cellular apoptosis. Furthermore, COS was found to inhibit the expression of immune checkpoint PD-L1. This study suggests that COS-modified PLGA nanoparticles with low toxicity and high encapsulation efficiency (EE) could potentially enhance drug efficacy.


Suitability of passive sampling for the monitoring of pharmaceuticals in Finnish surface waters.
The occurrence of five pharmaceuticals, consisting of four anti-inflammatory and one antiepileptic drug, was studied by passive sampling and grab sampling in northern Lake Päijänne and River Vantaa. The passive sampling was performed by using Chemcatcher® sampler with a SDB-RPS Empore disk as a receiving phase. In Lake Päijänne, the sampling was conducted during summer 2013 at four locations near the discharge point of a wastewater treatment plant and in the years 2013 and 2015 at four locations along River Vantaa. The samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The concentrations of carbamazepine, diclofenac, ibuprofen, ketoprofen, and naproxen in Lake Päijänne determined by passive sampling ranged between 1.4-2.9 ng L(-1), 15-35 ng L(-1), 13-31 ng L(-1), 16-27 ng L(-1), and 3.3-32 ng L(-1), respectively. Similarly, the results in River Vantaa ranged between 1.2-40 ng L(-1), 15-65 ng L(-1), 13-33 ng L(-1), 16-31 ng L(-1), and 3.3-6.4 ng L(-1). The results suggest that the Chemcatcher passive samplers are suitable for detecting pharmaceuticals in lake and river waters.


Data to estimate the similarity of tobacco research samples to intended populations.
This article presents mean and prevalence rates for demographic and smoking history characteristics for U.S. current smokers based on the 2000 National Health Interview Survey. Researchers can use these data to estimate the similarity of their sample to those of the typical U.S. smoker.


Fluorescence-based biosensing of zinc using carbonic anhydrase.
Measurement of free zinc levels and imaging of zinc fluxes remains technically difficult due to low levels and the presence of interfering cations such as Mg and Ca. We have developed a series of fluorescent zinc indicators based on the superb sensitivity and selectivity of a protein, human apo-carbonic anhydrase II, for Zn(II). These indicators transduce the level of free zinc as changes in intensity, wavelength ratio, lifetime, and/or anisotropy; the latter three approaches permit quantitative imaging of zinc levels in the microscope. A unique attribute of sensors incorporating biological macromolecules as transducers is their capability for modification by site-directed mutagenesis. Thus we have produced variants of carbonic anhydrase with improved affinity for zinc, altered selectivity, and enhanced binding kinetics, all of which are difficult to modify in small molecule indicators.


Isolation and radiation hybrid mapping of a dinucleotide repeat polymorphism at the human calcium-sensing receptor (CASR) locus.
Calcium-sensing receptor (CASR) in parathyroid gland regulates calcium homeostasis by sensing decreases in extracellular calcium levels and effecting an increase in secretion of parathyroid hormone. A polymorphic dinucleotide (CA) sequence was isolated from a genomic clone containing the human CASR gene and was mapped to 3q13.3-q21. This polymorphism will be useful in the genetic study of disorders affecting calcium metabolism, such as hypercalcemia, hypocalcemia, osteoporosis, hyperparathyroidism, and hypoparathyroidism.


Antibody-coupled siRNA as an efficient method for in vivo mRNA knockdown.
Knockdown of genes by RNA interference (RNAi) in vitro requires methods of transfection or transduction, both of which have limited impact in vivo. As a virus-free approach, we chemically coupled cell surface receptors internalizing antibodies to the short interfering RNA (siRNA) carrier peptide protamine using the bispecific cross-linker sulfo-SMCC (sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate). First, protamine was conjugated amino-terminally to sulfo-SMCC, and then this conjugate was coupled via cysteine residues to the IgG backbone to carry siRNA. This complex can efficiently find, bind and internalize into receptor-positive cells in vitro and in vivo, which can be checked by flow cytometry, fluorescence microscopy and western blotting. This method obtains results similar to those of siRNA targeting molecules engineered by genetic fusions between receptor-binding and siRNA carrier units, with the advantage of using readily available purified proteins without the need for engineering, expression and purification of respective constructs. The procedure for coupling the complex takes ∼ 2 d, and the functional assays take ∼ 2 weeks.


Preparation of Modified Beeswax and Its Influence on the Surface Properties of Compressed Poplar Wood.
Beeswax was modified through the direct blending of nano-TiO₂, chitosan, acid dyes, and neutral dyes. With the varied modified beeswax, hot waxing was conducted on compressed poplar wood. Treated wood surfaces were characterized with scanning electron microscopy and thermogravimetric analysis. Results show that the C, O, N, Au, S, and Ti elements in modified beeswax successfully penetrated into pits of compressed poplar wood, imparting rich colors to the wood surface. The blending of 10% (mass fraction) beeswax, 0.2% chitosan, and 0.05% neutral red was the best treatment for mulation for improving the in-surface staining uniformity, durability, surface gloss, contact angle, and texture conspicuity of compressed poplar.


Combined apocynin and carvedilol protect against cadmium-induced testicular damage via modulation of inflammatory response and redox-sensitive pathways.
Testicular damage is considered a severe complication of cadmium (Cd) exposure which is associated with tissue oxidative stress damage, inflammation, and apoptosis. The present study investigated the antioxidant, anti-inflammatory, and anti-apoptotic activities of apocynin (APO) and carvedilol (CVD) against Cd-induced acute testicular damage. Rats were allocated into five groups as follows: normal control (received vehicle), Cd control group (2 mg/kg, i.p), APO-treated group (25 mg/kg, P.O.), CVD-treated group (10 mg/kg, P.O.), and combination group (APO + CVD). Blood, serum, and tissue samples were withdrawn for hematological, biochemical, molecular, and histological analyses. The present results confirmed testicular damage after cd exposure as indicated by alteration of serum hormonal levels, hematological defects, histopathological changes, and loss of steroidogenic functions. Besides, Cd injection-induced up-regulation of NADPH oxidase, MDA, NF-κB, IRF3, MPO, pro-inflammatory cytokines, Bax, and cleaved caspase-3 expression concomitant with down-regulation of Nrf2, GSH, SOD, and Bcl2 expression. Interestingly, pretreatment with APO and/or CVD significantly relieved Cd-induced testicular damage at cellular and molecular levels. Notably, the combined protective effect of APO plus CVD was higher than the protective effect of each drug alone. Overall, combined APO and CVD could serve as a good candidate for protection against Cd-induced testicular damage via suppression of inflammatory response and modulation of the redox-sensitive pathway.


High-sensitivity C-reactive protein is not independently associated with self-reported infertility in National Health and Nutrition Examination Survey 2015-2018 data.
To study the association between high-sensitivity C-reactive protein (hs-CRP) and infertility among reproductive-age women while controlling for obesity and other metabolic markers. Previous studies found a link between infertility and cardiovascular diseases (CVDs). C-reactive protein is a sensitive marker of CVDs, and its levels are affected by obesity. We conducted a cross-sectional study using national data from 2015 through 2018. A total of 940 women aged 20-45 years who self-reported infertility, had hs-CRP values measured, and did not have CRP >10 mg/L, asthma, arthritis, bronchitis, thyroid disease, bilateral oophorectomy, hysterectomy, and who were not breastfeeding or pregnant, premenarchal at the time of study or had menarche after the age of 20. N/A. Infertility status (ever reporting inability to conceive with 12 months of trying to become pregnant). In comparison to noninfertile women, self-reported infertile women had higher mean of hs-CRP (3.11 mg/L vs. 2.40 mg/L) and higher percentage of moderate/high hs-CRP values (77.0% vs 58.8%). However, after adjusting for metabolic markers, there was a nonsignificant association between moderate/high hs-CRP and self-reported infertility in the multivariable logistic regression analysis. Odds ratio estimates of the association between hs-CRP and infertility increased over 40% after removing obesity measures and/or high-density lipoprotein from regression models. There was no association between hs-CRP and self-reported infertility after controlling for obesity measures and other risk factors for CVDs in a sample of U.S. women aged 20-45 years.


Nonmodular oscillator and switch based on RNA decay drive regeneration of multimodal gene expression.
Periodic gene expression dynamics are key to cell and organism physiology. Studies of oscillatory expression have focused on networks with intuitive regulatory negative feedback loops, leaving unknown whether other common biochemical reactions can produce oscillations. Oscillation and noise have been proposed to support mammalian progenitor cells' capacity to restore heterogenous, multimodal expression from extreme subpopulations, but underlying networks and specific roles of noise remained elusive. We use mass-action-based models to show that regulated RNA degradation involving as few as two RNA species-applicable to nearly half of human protein-coding genes-can generate sustained oscillations without explicit feedback. Diverging oscillation periods synergize with noise to robustly restore cell populations' bimodal expression on timescales of days. The global bifurcation organizing this divergence relies on an oscillator and bistable switch which cannot be decomposed into two structural modules. Our work reveals surprisingly rich dynamics of post-transcriptional reactions and a potentially widespread mechanism underlying development, tissue regeneration, and cancer cell heterogeneity.


A protective, single-visit TB vaccination regimen by co-administration of a subunit vaccine with BCG.
The only licensed tuberculosis (TB) vaccine, Bacillus Calmette Guerin (BCG), fails to reliably protect adolescents and adults from pulmonary TB, resulting in ~1.6 million deaths annually. Protein subunit vaccines have shown promise against TB in clinical studies. Unfortunately, most subunit vaccines require multiple administrations, which increases the risk of loss to follow-up and necessitates more complex and costly logistics. Given the well-documented adjuvant effect of BCG, we hypothesized that BCG co-administration could compensate for a reduced number of subunit vaccinations. To explore this, we developed an expression-optimized version of our H107 vaccine candidate (H107e), which does not cross-react with BCG. In the CAF®01 adjuvant, a single dose of H107e induced inferior protection compared to three H107e/CAF®01 administrations. However, co-administering a single dose of H107e/CAF®01 with BCG significantly improved protection, which was equal to BCG co-administered with three H107e/CAF®01 doses. Importantly, combining BCG with a single H107e/CAF®01 dose also increased protection in previously BCG-primed animals. Overall, a single dose of H107e/CAF®01 with BCG induced long-lived immunity and triggered BCG-specific Th17 responses. These data support co-administration of BCG and subunit vaccines in both BCG naïve and BCG-primed individuals as an improved TB vaccine strategy with reduced number of vaccination visits.


Multi-configurational quantum chemical studies of the Tc2X8(n-) (X = Cl, Br; n = 2, 3) anions. Crystallographic structure of octabromoditechnetate(3-).
The [Cs((2 + x))][H(3)O((1 - x))]Tc(2)Br(8)·4.6H(2)O (x = 0.221) salt has been synthesized and characterized by single crystal XRD. Multi-configurational quantum chemical calculations on Tc(2)X(8)(n-) (X = Cl, Br; n = 2, 3) have been performed and indicate the π component in the Tc-Tc bond to be stronger for n = 3.


A case report of cor pulmonale in a woman without exposure to tobacco smoke: an example of the risks of indoor wood burning.
We present the case of a 67-year-old woman with chronic cor pulmonale. She never smoked tobacco and had no other risk factors for pulmonary disease. In developed nations, chronic obstructive lung disease and cor pulmonale are overwhelmingly associated with tobacco use. However, indoor air pollution, most commonly due to burning of solid biomass fuel such as wood, can cause similar clinical syndromes. At our teaching hospital, there is an epidemic of chronic cor pulmonale among nonsmoking women. We attribute this sex predilection to women's greater exposure to wood smoke. Physicians must be cognizant of its risks and counsel patients on prevention strategies such as improved ventilation.


Delivery of roxarsone via chicken diet→chicken→chicken manure→soil→rice plant.
Roxarsone (ROX), a widely used feed additive, occurs as itself and its metabolites in animal manure. Rice is prone to accumulate As than other staple food. Four diets with 0, 40, 80 and 120mgROXkg(-1) were fed in chickens, and four chicken manures (CMs) were collected to fertilize rice plants in a soil culture experiment. Linear regression analysis shows that the slopes of As species including 4-hydroxy-phenylarsonic acid, As(V), As(III), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in CM versus dietary ROX were 0.033, 0.314, 0.033, 0.054 and 0.138, respectively. Both As(III) and DMA were determined in all rice grains, and As(III), As(V), MMA and DMA in rice hull, but detectable As forms in rice straws and soils increased with increasing ROX dose. Grain As(III) was unrelated to ROX dose but exceeded the Chinese rice As limit (0.15mgAs(III)kg(-1)). Dietary ROX enhanced straw As(III) mostly, with the slope of 0.020, followed by hull DMA (0.006) and grain DMA (0.002). The slopes of soil As(V) and As(III) were 0.003 and 0.001. This is the first report illustrating the quantitative delivery of ROX via food chain, which helps to evaluate health and environmental risks caused by ROX use in animal production.


Analysis of incision depth following experimental radial keratotomy.
Eight-incision radial keratotomy was performed on a series of cadaver eyes using ultrasonic pachymetry and both metal and diamond blades. There were no statistically significant differences in mean corneal flattening (approximately 9.5 diopters) obtained with either the diamond or metal blades. Short diamond knife incisions produced less flattening that was statistically significant (5.8 diopters). Histologic analysis of incision depth revealed similar results with both the diamond (84%) and metal (86%) blades.


DFT calculations of the anomeric and exo-anomeric effect of the hydroperoxy and peroxy groups.
DFT calculations were carried out on axially and equatorially oriented 2-hydroperoxy and 2-peroxy tetrahydropyran, cyclohexyl hydroperoxide, hydroperoxides of 2,3-unsaturated hexapyranoses, and hydroperoxides of OMe and OBn substituted derivatives of 2-deoxy-glucopyranose and 2-deoxy-galactopyranose to investigate the anomeric and exo-anomeric effects of these groups. The structure and energy of the conformers were calculated at the B3LYP/6-311++G** level. Calculations showed that the peroxy anion group exhibits a strong anomeric effect, comparable in magnitude to the methoxy group, and that the anomeric effect of the hydroperoxy group is similar to the hydroxyl group. These results revealed that hydroperoxy and peroxy anion groups display an exo-anomeric effect, but the orientation around the C1-O1 bond is also affected by hydrogen bonding and electrostatic interactions.


The establishment of a laboratory colony of Ixodes holocyclus.
A laboratory colony capable of producing annually 3000 female Ixodes holocyclus was maintained for 3 years. Guinea-pigs were used for larval feeding and bandicoots for nymphs and adults. The methods and equipment employed are described in detail.


Initial assessment of treatment of talar posterior process fractures with open reduction and percutaneous fixation.
The purpose of this study was to provide an initial assessment of treatment for talar posterior process fractures using open reduction and internal fixation (ORIF) through posteromedial approach and percutaneous screw fixation. From January 2014 to December 2018, 12 cases with displaced fracture of talar posterior process were treated in our department. The clinical and radiological results were assessed after 4 and 12 months of operation with Visual Analog Scale (VAS) pain and American Orthopedic Foot and Ankle Society (AOFAS) scores. ORIF was performed in four of the cases and percutaneous screw fixation was performed in eight of the cases. The average follow-up period was 13 months. Complications such as wound infection, nerve injury, screw loosening, malunion or nonunion of fracture were absent. For clinical assessment, considerable mprovements were observed for the AOFAS and VAS scores at 4 and 12 months postoperatively for both techniques. There was no significant difference for AOFAS scores and VAS scores between the two techniques (p > 0.05). Both techniques showed good functional outcome and were performed for posterior talar process fracture following the fracture displacement guidelines. Percutaneous screw fixation treatment with computer-assisted three-dimensional evaluation shortened the operation time and reduced incidences of surgical complications.


"Functional communication between IP3R and STIM2 at subthreshold stimuli is a critical checkpoint for initiation of SOCE".
The family of stromal interaction molecules (STIMs), comprising the homologs STIM1 and STIM2 with their different isoforms, has an intricate role in cellular calcium (Ca2+) homeostasis and signal transduction. While this is predominantly accomplished in concert with plasma membrane Orai proteins, STIM1 and STIM2 show essential functional differences, as was recently further elucidated by Ahmad et al. [1].


Low Tongue Strength and the Number of Teeth Present Are Associated with Cognitive Decline in Older Japanese Dental Outpatients: A Cross-Sectional Study.
To mitigate the impact of dementia, initiating early intervention is important. This study aims to investigate the associations between deterioration in oral function and cognitive decline in older outpatients whose oral health was maintained in the dental clinic. This study included 50 outpatients aged ≥65 years. We used the Japanese version of the Montreal Cognitive Assessment (MoCA-J) to assess cognitive decline. Oral function was evaluated by tongue pressure, masticatory performance, and swallowing ability. A full-mouth periodontal examination was conducted, and the occlusal support and number of teeth were recorded. Odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive decline (MoCA-J score ≤ 25 points) were calculated using logistic regression models. The age, number of teeth, tongue pressure, and masticatory performance were significantly correlated with cognitive decline (p < 0.05). Logistic regression analyses revealed that cognitive decline was independently associated with age (OR: 1.25; 95% CI: 1.03-1.52; p = 0.024), number of teeth (OR = 0.83; 95% CI: 0.76-1.00; p = 0.047), and lower tongue pressure (OR: 0.87; 95% CI: 0.77-0.98; p = 0.022). Lower tongue pressure and a small number of remaining teeth may be associated with cognitive decline in Japanese outpatients.


An electron microscopic study of the developing caudate nucleus in euthyroid and hypothyroid states.
Thyroid hormone exerts a powerful influence on CNS growth and maturation. Hypothyroidism early in life has long been known to cause disturbances in innate behavior, motor performance, severe and frequently irreversible mental retardation. In this deficiency, depressed caudate neurogenesis, cell migration and neuropil development during the rapid period of CNS growth may contribute to the clinical picture of perceptual handicaps often seen in cretins. Light microscopic and Golgi studies of the developing caudate nucleus in thyroid deficiency have been carried out to help attain insights into the mechanisms whereby the extrapyramidal system regulates motor function. The ultrastructural study of caudate nuclear cytogenesis and synaptogenesis in normal and hypothyroid states provides more detailed information for further analysis of the problem. Hypothyroidism was induced from birth by adding prophylthiouracil to the food and drinking water of lactating dams. Linear development of the caudate nucleus of both normal and hypothyroid rats at ages 8, 14, 20, 30 and 42 days was studied by electron microscopy. Thyroid glands were examined by light microscopy to assess the normal and deficient states. Immature cells, primitive processes and synapses were the characteristic features of the 8-day-old normal caudate nucleus. Distinctively wide cisternae of the rough endoplasmic reticulum, loosley packed Golgi apparatus and chromatin clumps throughout the nuclei of the neurons were significant early morphologic variations. The dramatic cytoarchitectural maturation in the 14- and 20-day normal caudate neuropil points to the rapidity of developmental rate. After the growth spurt of the first three weeks a maturational plateau occurs which is characterized by well-formed neuronal cytoplasmic organelles, myelinated and non-myelinated axons, axon terminals, dendrites and their spines, and synapses. Thyroid deficiency causes a marked maturational delay of approximately 7 days in caudate neuronal proliferation, the elaboration of neuronal networks and the attainment of mature synaptic contents and membranes. This delay is evidenced by comparison of the structural similarities between 8-day-old normal and 14-day-old deficient rats; and additional comparisons between the 14-day-old normal and 20-day-old hypothyroid rats. A rapid "catch up" process in fine structural morphogenesis takes place in the period between days 14 and 30 in the deficient animals. Repression of thyroid function does not entirely prevent development of the caudate nucleus but allows a fairly extensive, though critically incomplete degree of maturation. This imperfection is manifested by a decrease in the number of synaptic contacts that persists even after the rapid "catch up" phenomenon of caudate synaptogenesis.


Preconception care. An integral part of primary care for women.
Preconception health care should be an integral part of primary health care services for all women with the potential for childbearing. This article delineates those aspects of preconception care that should be included in a well woman visit. Specific interventions for risks identified in the preconception health care visit are reviewed. Finally, the importance of preconception health care in reducing poor perinatal outcome and promoting overall good health is discussed.


A novel peptide derived from the mannose binding lectin inhibits LPS-activated TLR4/NF-κB signaling and suppresses ocular inflammation.
Uveitis is a major cause of vision impairment worldwide. Current treatments have limited effectiveness but severe complications. Mannose binding lectin (MBL) is an important protein of the innate immune system that binds to TLR4 and suppresses LPS-induced inflammatory cytokine secretion. MBL-mediated inhibition of inflammation via the TLR4 pathway and MBL-derived peptides might be a potential therapeutics. In this study, we designed a novel MBL-derived peptide, WP-17, targeting TLR4. Bioinformatics analysis was conducted for the sequence, structure and biological properties of WP-17. The binding of WP-17 to THP-1 cells was analyzed using flow cytometry. Signaling molecules were analyzed by western blotting, and activation of NF-κB was measured by immunofluorescence-histochemical analysis. Effects of WP-17 were studied in vitro using LPS-stimulated THP-1 cells and in vivo in endotoxin-induced uveitis (EIU). Our results showed that WP-17 could bind to TLR4 expressed on macrophages, thus downregulating the expression levels of MyD88, IRAK-4, and TRAF-6, and inhibiting the downstream NF-kB signaling pathway and LPS-induced expression of TNF-α and IL-6 in THP-1 cells. Moreover, in EIU rats, intravitreal pretreatment with WP-17 demonstrated significant inhibitory effects on ocular inflammation, attenuating the clinical and histopathological manifestations of uveitis, reducing protein leakage and cell infiltration into the aqueous humor, and suppressing TNF-α and IL-6 production in ocular tissues. In summary, our study provides the first evidence of a novel MBL-derived peptide that suppressed activation of the NF-кB pathway by targeting TLR4. The peptide effectively inhibited rat uveitis and may be a promising candidate for the management of ocular inflammatory diseases.


Fractures of the calcaneus.
Displaced fractures of the calcaneous are relatively common injuries that remain a treatment enigma. Virtually all aspects of the management of calcaneal fractures are a source of debate. Contemporary imaging, reduction, and fixation techniques attempt to improve the long term results of these injuries. The complex fracture fragments displace in predictable patterns. Meticulous surgical technique, restoration of extra- and intra-articular anatomy, and obtaining rigid fracture fixation are critical to obtaining satisfactory operative results. This article extensively reviews the controversies and summarizes the current opinions in the management of displaced calcaneal fractures.


The Role of Angiopoietins in Neovascular Diabetes-Related Retinal Diseases.
Diabetic retinopathy is a devastating and frequent complication of poorly controlled diabetes, whose pathogenesis is still only partially understood. Advances in basic research over the last two decades have led to the discovery of angiopoietins, proteins that strongly influence the growth and integrity of blood vessels in many vascular beds, with particular importance in the retina. Angiopoietin 1 (Ang1), produced mostly by pericytes and platelets, and angiopoietin 2 (Ang2), produced mainly by endothelial cells, bind to the same receptor (Tie2), but exert opposing effects on target cells. Ang1 maintains the stability of the mature vasculature, while Ang2 promotes vessel wall destabilization and disruption of the connections between endothelial cells and pericytes. Human retinal endothelial cells exposed to Ang2 show reduced membrane expression of the adhesion molecule VE-cadherin, and patients with proliferative diabetic retinopathy or diabetic macular edema have markedly increased vitreal concentrations of Ang2. Faricimab, a bi-specific antibody simultaneously directed against Ang2 and VEGF, has shown promising results in clinical trials among patients with diabetic retinopathy, and other agents targeting the angiopoietin system are currently in development.


Do Bisexuals Have a Bisexual Viewing Pattern?
Past visual attention research appears to show that bisexual men and women view erotic images differently compared to heterosexual and gay/lesbian men and women. However, none of these studies have employed analytic approaches required to determine whether these apparent bisexual viewing patterns are due to averaging together heterosexual and gay/lesbian type viewing patterns, or rather are because bisexual-identified individuals possess unique viewing patterns which are distinct from heterosexual and gay/lesbian individuals. In the current eye-tracking study, we aimed to address this question. Visual attention of 60 men (24 heterosexual, 19 gay, 17 bisexual) and 54 women (21 heterosexual, 10 lesbian, 23 bisexual) was tracked, while they viewed erotic images of nude men and women. Applying analytic approaches capable of detecting bisexual responding revealed that bisexual men, but not bisexual women, had a unique bisexual controlled attention pattern, and that neither bisexual men nor women demonstrated a unique bisexual pattern of initial attention. Our findings provide mixed evidence for a unique bisexual attentional profile in men and women.


Robertsonian translocations in Mus musculus from Sicily.
The karyotypes of 6 mice from different places in Sicily have been determined. 3 of them had abnormal chromosome numbers of 2n = 26, 2n = 27 and 2n = 29, caused by Robersonian translocations of one acrocentric chromosome to another resulting in metacentric chromosomes. The newly described metacentric chromosomes are Rb(4.3)1Sic, Rb(15.2)2SIC, Rb(12.6)3SIC, Rb(13.5)4Sic, Rb(14.10)5Sic, Rb(17.8)6Sic and Rb(16.9)7Sic.


Crystal structure of 2-[(naphthalen-2-yl)meth-yl]iso-thio-uronium bromide.
Herein we report the crystal structure of 2-[(naphthalen-2-yl)meth-yl]iso-thio-uronium bromide, C12H13N2S+·Br-, which crystallizes in the monoclinic P21/c centrosymmetric space group. The asymmetric unit contains one 2-[(naphthalen-2-yl)meth-yl]iso-thio-uronium cation and one bromide anion. The methyl-ene carbon lies in plane of the naphthalene core. In comparison with reference structures, elongation of C-S bonds as well as tilting of the iso-thio-uronium group is observed. Given the ionic nature of the compound, the structure is held by charge-assisted N-H⋯Br hydrogen bonds, with a noteworthy contribution of dipole-dipole inter-actions, which form bilayers in the structure. The bilayers are held by the weak London forces.


Which bisphosphonates do oncologists prescribe for women with metastatic breast cancer and why? Results of a UK survey.
In breast cancer, many bisphosphonates are approved for use in metastatic bone disease which significantly delay and reduce the risk and rate of skeletal complications. There is a paucity of evidence about the relative efficacy of different drugs, routes of administration or optimal doses. Oral and IV administration have various advantages and disadvantages. A total of 112/144 (78%) UK oncologists completed a postal survey about their bisphosphonate prescribing practices and reasons for them. Fifty three percent gave both oral and IV drugs, 40% only IV and 7% only oral. In the absence of scientific evidence, financial constraints often dictated choice and route of administration or local guidelines which were extremely varied. The primary advantages perceived for oral drugs were patient convenience (48%) and for IV to ensure compliance or bioavailability (37%). Adherence to oral bisphosphonates is often poor, but 44% oncologists expected good adherence in >71% patients. More clinical trial data are needed to inform practice.


Clinical characterization, disability, and mortality in people with strokes during 90 days.
to describe clinical characteristics and mortality of people with ischemic cerebrovascular accidents (strokes); to compare disability before the event and 90 days after. longitudinal study with 308 people hospitalized in Salvador-BA. Data collection took place from 03/2019 to 01/2020. Descriptive and inferential statistics were used. mean age was 64.8 years, and National Institute of Health Stroke Scale score was 10.7. The median length of stay in the hospital was 11 days. Afro-descendants predominated (84%), elementary educational level (68.4%), income up to three minimum wages (89.1%), arrival within 4.5 hours of symptoms (57.9%) and admission to a specialized unit (71.8%). Prevalence of thrombolysis: 26%. The asymptomatic before the event category predominated (85.3%) as did the moderate/severe disability (41.5%) after 90 days. 19.7% of the sample evolved to death. Conclusions: the high mortality and disability generated by the event have implications for health management and care.


Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer.
Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea. Women (n=59, mean age 42.6 years [(range 23.3-52.5]) with eBC were recruited before any treatment. Pretreatment ovarian reserve markers (anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status at 2 years. Pretreatment AMH was significantly lower in women with amenorrhoea at 2 years (4.0 ± 0.9 pmol/L versus 17.2 ± 2.5, P<0.0001), but FSH and inhibin B did not differ between groups. By logistic regression, pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of ovarian status at 2 years (P=0.005; odds ratio 0.013). We combined these data with a similar cohort (combined n=75); receiver-operator characteristic analysis for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82-0.97)). A cross-validated classification tree analysis resulted in a binary classification schema with sensitivity 98.2% and specificity 80.0% for correct classification of amenorrhoea. Pretreatment AMH is a useful predictor of long term post chemotherapy loss of ovarian function in women with eBC, adding significantly to the only previously established individualising predictor, i.e. age. AMH measurement may assist decision-making regarding treatment options and fertility preservation procedures.


Mild hypothermia reduces ventilator-induced lung injury, irrespective of reducing respiratory rate.
In the era of lung-protective mechanical ventilation using limited tidal volumes, higher respiratory rates are applied to maintain adequate minute volume ventilation. However, higher respiratory rates may contribute to ventilator-induced lung injury (VILI). Induced hypothermia reduces carbon dioxide production and might allow for lower respiratory rates during mechanical ventilation. We hypothesized that hypothermia protects from VILI and investigated whether reducing respiratory rates enhance lung protection in an in vivo model of VILI. During 4 h of mechanical ventilation, VILI was induced by tidal volumes of 18 mL/kg in rats, with respiratory rates set at 15 or 10 breaths/min in combination with hypothermia (32°C) or normothermia (37°C). Hypothermia was induced by external cooling. A physiologic model was established. VILI was characterized by increased pulmonary neutrophil influx, protein leak, wet weights, histopathology score, and cytokine levels compared with lung protective mechanical ventilation. Hypothermia decreased neutrophil influx, pulmonary levels, systemic interleukin-6 levels, and histopathology score, and it tended to decrease the pulmonary protein leak. Reducing the respiratory rate in combination with hypothermia did not reduce the parameters of the lung injury. In conclusion, hypothermia protected from lung injury in a physiologic VILI model by reducing inflammation. Decreasing the respiratory rate mildly did not enhance protection.


Two cases with fulminant type 1 diabetes that developed long after cessation of immune checkpoint inhibitor treatment.
Various immune-related adverse events (irAEs), including fulminant type 1 diabetes (FT1D), are known to be associated with immune checkpoint inhibitors (ICIs). We experienced two lung adenocarcinoma cases who developed fulminant type 1 diabetes long after discontinuation of ICI therapies. One, a 74-year-old male, received nivolumab and developed fulminant type 1 diabetes 44 days after the last infusion. The other, an 85-year-old male, received atezolizumab and developed fulminant type 1 diabetes 171 days after the last infusion. Clinical ICI treatment guidelines recommend laboratory tests during ICI treatments but the necessity of tests in patients whose ICI therapy has been discontinued is not clearly described. These cases indicate that blood glucose monitoring should be continued at least for several months, and that patients should be informed of the possibility of fulminant type 1 diabetes after ICI discontinuation, because fulminant type 1 diabetes progresses rapidly and can be life-threatening if not promptly recognized.


The genome sequence of Sea-Island cotton (Gossypium barbadense) provides insights into the allopolyploidization and development of superior spinnable fibres.
Gossypium hirsutum contributes the most production of cotton fibre, but G. barbadense is valued for its better comprehensive resistance and superior fibre properties. However, the allotetraploid genome of G. barbadense has not been comprehensively analysed. Here we present a high-quality assembly of the 2.57 gigabase genome of G. barbadense, including 80,876 protein-coding genes. The double-sized genome of the A (or At) (1.50 Gb) against D (or Dt) (853 Mb) primarily resulted from the expansion of Gypsy elements, including Peabody and Retrosat2 subclades in the Del clade, and the Athila subclade in the Athila/Tat clade. Substantial gene expansion and contraction were observed and rich homoeologous gene pairs with biased expression patterns were identified, suggesting abundant gene sub-functionalization occurred by allopolyploidization. More specifically, the CesA gene family has adapted differentially temporal expression patterns, suggesting an integrated regulatory mechanism of CesA genes from At and Dt subgenomes for the primary and secondary cellulose biosynthesis of cotton fibre in a "relay race"-like fashion. We anticipate that the G. barbadense genome sequence will advance our understanding the mechanism of genome polyploidization and underpin genome-wide comparison research in this genus.


Eryngin, a novel antifungal peptide from fruiting bodies of the edible mushroom Pleurotus eryngii.
An antifungal peptide with a molecular mass of 10k Da was isolated from fruiting bodies of the mushroom Pleurotus eryngii. The peptide, designated as eryngin, inhibited mycelial growth in Fusarium oxysporum and Mycosphaerella arachidicola. It was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and S-Sepharose. Its N-terminal sequence demonstrated some similarity to the antifungal protein from the mushroom Lyophyllum shimeiji and little resemblance to thaumatin and thaumatin-like proteins.


Physical activity, cardiorespiratory fitness, and cognitive function in postmenopausal women with breast cancer.
Physical activity may improve cognitive function in women with breast cancer. In a cross-sectional study, we explored the relationship between cognitive function and physical activity (actigraph) and cardiorespiratory fitness (sub-maximal graded exercise test) in 73 postmenopausal women with early stage breast cancer prior to the initiation of systemic adjuvant therapy. Cognitive function was assessed with a standardized battery of neurocognitive measures assessing eight domains. Data were analyzed using partial correlations, controlling for age and total hours of actigraph wear-time. Women were, on average, 63.71 (± 5.3) years of age with 15.47 (± 2.48) years of education. For physical activity, greater average number of steps per day were associated with better attention (r = .262, p = .032) and psychomotor speed (r = .301, p = .011); greater average hours of moderate and moderate/vigorous intensity physical activity were associated with better visual memory (r = .241, p = .049; r = .241, p = .049, respectively); and greater average daily energy expenditure was associated with better visual memory (r = .270, p = .027) and psychomotor speed (r = .292, p = .017). For fitness, higher peak maximum VO2 was associated with better concentration (r = .330, p = .006), verbal memory (r = .241, p = .048), and working memory (r = .281, p = .019). These results suggest that higher levels of physical activity and cardiorespiratory fitness are associated with better cognitive function in postmenopausal women with breast cancer. Randomized controlled trials (RCT) to examine whether physical activity improves cognitive function in women with breast cancer are warranted. These RCTs should also determine the mechanisms of the influence of physical activity on cognitive function. CLINICAL TRIALS REGISTRATION NUMBER: NCT02793921; Date: May 20, 2016.


A three-dimensional visualization of the full-field surgical region based on thin-slice MRI: A helpful approach for simultaneously guiding tumor resection and perforator flap elevation.
The goal of the current study was to explore the application of preoperative three-dimensional reconstruction (3DR) based on thin-slice magnetic resonance imaging (MRI) in the simultaneous guidance of en bloc tumor resection and adjacent perforator flap elevation. The prospective cohort included 35 patients diagnosed with either soft tissue sarcoma or squamous cell skin cancer between 2019 and 2021. The preoperative 3DR based on thin-slice MRI illustrated the spatial anatomical relationship among the tumor, underlying muscle, adjacent perforator vessels, and bone around the surgical region. The accuracy of preoperative imaging data was verified by intraoperative vessel dissection and postoperative pathological measurements. Tumor size from 3DR data showed relatively high concordance rates with pathological measurements within the 95% limits of agreement. An average of three perforators (range: 1-7) with a mean diameter of 0.32 cm (range: 0.18-0.74 cm) from the 3DR were present in our study. The average distance between tumor boundary and perforator piercing sites on the 3DR was 2.2 cm (range: 1.2-7.7 cm). The average length of artery perforator coursing along the subcutaneous tissue was 5.8 cm (range: 3.3-25.1 cm). The mean flap harvest time was 55 mins (range: 36-97 min). The average flap size was 92.2 cm2 (range: 32-126 cm2). One perforator flap occurred distal partial necrosis. A thorough understanding of anatomical structures in the surgical region according to full-field 3DR based on thin-slice MRI can improve the performance of radical resection of the tumor and adjacent perforator flap transfer, especially for junior surgeons with a poor experience.


[Effect of unithiol and acetylcysteine on lipid peroxidation and the erythrocyte antioxidant system in sensitized guinea pigs].
The effect of unithiol and acetylcysteine on lipid peroxidation, thioldisulfide equilibrium, glucose-6-phosphate dehydrogenase, glutathione reductase and lactate dehydrogenase activity and on erythrocyte resistance was studied in guinea-pigs during sensitization with C. maltosa. Sensibilized animals receiving thiol antioxidants showed partial restoration of normal biochemical levels.


Sensitive high-performance liquid chromatographic method using coulometric electrode array detection for measurement of phytoestrogens in dried blood spots.
As the epidemiological and physiological investigation of isoflavones and lignans expands, the need for sensitive methods for analyzing large numbers of samples intensifies. We have developed a method using high-performance liquid chromatography (HPLC) equipped with a coulometric electrode array detector for separation and sensitive detection of daidzein (Da), equol (Eq), genistein (Ge) and enterolactone (Enl) in dried blood spots (DBS). Detection limits ranged from 4.5 pg or 0.09 ng/mL (Eq) to 19 pg or 0.38 ng/mL (Ge) on column. Signal linearities ranged from detection limits to 200 ng/mL (Eq, Enl) and 600 ng/mL (Da, Ge) sample concentration. Correlations between DBS and serum concentrations were 0.66 (Enl), 0.88 (Eq), 0.98 (Ge) and 0.99 (Da). Intra-assay coefficients of variation (CVs) were less than 8% and inter-assay CVs ranged from 2.4 to 20.2% for Da, Eq and Ge for three levels of controls. Enl intra-assay CV was 13.6% for the low pooled control. Analytic recovery ranged from 87% (inter-assay Ge) to 98% (inter-assay Enl). DBS concentrations of Da, Ge and Eq were stable for at least 8 weeks at 4 and 25 degrees C, and at 37 degrees C for at least 5 weeks, with Enl showing greater variability at all temperatures but relative stability for 7 weeks. Measurement of samples from 135 perimenopausal Japanese women consuming habitual diets in Kyoto and Fukushima prefectures showed the former to have the expected lower concentrations of Da and Eq (416 and 87 nM) as well as Enl (49 nM) compared to the latter locale (566, 145 and 72 nM, respectively). This method could be useful in large epidemiological research or detailed physiological studies.


Fibrin sealing versus stapling of hernia meshes in an onlay model in the rat.
Incisional and inguinal hernia repair are among the most common procedures of general surgery. Mesh fixation by means of staples or sutures may lead to severe complications. The use of fibrin sealant (FS) has been suggested as alternative, but data on biocompatibility and adhesive strength of FS in combination with macroporous meshes is limited. Ventral hernia (n = 8 per group) was treated in rats in onlay technique with two types of meshes, fibrin sealed or stapled. TI-Mesh (TMxl) extralight and VYPROII (VPII) were tested 17 days post op. No failure in mechanical tests (tensile and burst strength) occurred in sealed or stapled meshes. Histology revealed equally good tissue integration and neovascularization in all groups. Fibrin sealant yields excellent fixation in experimental hernia repair. This rat model is suitable for testing meshes and fixation techniques.


The intergenic region between the Vicia faba chloroplast tRNA(CAALeu) and tRNA(UAALeu) genes contains a partial copy of the split tRNA(UAALeu) gene.
A cluster of three tRNA genes located on fragment Bam6a from Vicia faba chloroplast DNA has been sequenced: it contains the genes for tRNA(CAALeu), tRNA(UAALeu) and tRNA(Phe). The two tRNA(Leu) genes are separated by 443 bp and are transcribed divergently from different DNA strands. The intergenic region contains a series of short repeats and a partial copy of the split tRNA(UAALeu) gene which includes 100 bp of the 5' flanking region, 35 bp of the 5'exon and the first 42 bp of the intron. It is possible that some of these duplications occurred upon the rearrangement of the two tRNA(Leu) genes in broad bean (and in pea) or upon the deletion of one copy of the inverted repeat, since in all other higher plant chloroplast genomes studied so far these two tRNA(Leu) genes are located far apart on the genome, one being in the inverted repeat region, the other one in the large single copy region. The tRNA(Phe) and tRNA(UAALeu) are encoded by the same DNA strand, and separated by 110 bp.


Point of Care Diagnosis of Anemia Using Portable Auto Analyzer.
We describe a method for capillary blood sample-based point-of care testing of hemoglobin in population-based surveys using an automated analyzer system. The accuracy and precision of this method was comparable to hemoglobin estimated from venous blood sample (mean difference (SD) =0.2 (-2.77, 3.2), Pearson correlation coefficient, (0.969).


Ictal EEG patterns in band heterotopia.
Band heterotopia (BH) or "double cortex" syndrome is a neuronal migration disorder resulting in a diffuse band of subcortical grey matter and variable abnormality of the overlying cortex. Patients with BH have a spectrum of psychomotor delay and seizures. Associated epileptic syndromes and interictal EEG findings have been described, but ictal EEG patterns are lacking. We describe the clinical, interictal, and ictal EEG findings in two girls with BH and intractable seizures. Ictal EEG patterns correlated well with clinical seizure types, and did not have features unique to BH. Similarly, seizure behaviors and interictal EEG findings were typical of those seen in symptomatic generalized epilepsies. Despite evidence implicating the ectopic grey matter in seizure discharges, we conclude that seizure semiology and associated ictal EEG patterns in BH are no different from those seen in other causes of symptomatic generalized epilepsies.


Planes, trains, and automobiles: How cells localize their molecules.
In this issue of Molecular Cell, Gasparski et al.1 and Loedige et al.2 reshape our understanding of subcellular gene product localization by highlighting the importance of messenger RNA (mRNA) stability and co-translational mechanisms in mRNA and protein localization.


Gradual painless visual loss: anterior segment causes.
There are estimated to be 40 million blind individuals throughout the world. The majority of blind people in developing and developed countries are older adults. As the number of people over 60 years of age increases, the number of blind people also will increase. The primary care physician can play a major role in diagnosing and preventing many blinding diseases. This article discusses some of the major anterior segment causes of visual impairment in older adults in the industrialized nations.


Ten polymorphisms of estrogen-metabolizing genes and a family history of colon cancer--an association study of multiple gene-gene interactions.
Estrogen replacement therapy is associated with a reduced risk of colon cancer. Therefore, we evaluated the following ten estrogen metabolism-associated single-nucleotide polymorphisms (SNPs) by sequencing-on-chip technology using solid-phase polymerase chain reaction (PCR) on oligonucleotide microarrays: catechol-O-methyltransferase (COMT) Val158Met G-->A, 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17) vlV A-->C, cytochrome P-450 (CYP) 17 A2 allele T-->C, CYP1A1 MspI RFLP T-->C, CYP1A1 Ile462Val A-->G, CYP19 Arg264Cys C-->T, CYP19 C1558T C-->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor (ER) alpha IVS1 -401-->C in 76 patients with a family history of colon cancer and 722 healthy controls. Using stepwise logistic regression models, we found that none of the investigated SNPs is associated with a family history of colon cancer in a univariate and multivariate logistic regression model. In addition, when all two-way interactions of the investigated SNPs were ascertained, no significant interactions between SNPs were observed. In conclusion, we found no association between the carriage of one or multiple SNPs of the estrogen metabolism and a family history of colon cancer.


Drain after elective laparoscopic cholecystectomy. A randomized multicentre controlled trial.
Routine drainage after laparoscopic cholecystectomy is still debatable. The present study was designed to assess the role of drains in laparoscopic cholecystectomy performed for nonacutely inflamed gallbladder. After laparoscopic gallbladder removal, 53 patients were randomized to have a suction drain positioned in the subhepatic space and 53 patients to have a sham drain. The primary outcome measure was the presence of subhepatic fluid collection at abdominal ultrasonography, performed 24 h after surgery. Secondary outcome measures were postoperative abdominal and shoulder tip pain, use of analgesics, nausea, vomiting, and morbidity. Subhepatic fluid collection was not found in 45 patients (84.9 %) in group A and in 46 patients (86.8 %) in group B (difference 1.9 (95 % confidence interval -11.37 to 15.17; P = 0.998). No significant difference in visual analogue scale scores with respect to abdominal and shoulder pain, use of parenteral ketorolac, nausea, and vomiting were found in either group. Two (1.9 %) significant hemorrhagic events occurred postoperatively. Wound infection was observed in three patients (5.7 %) in group A and two patients (3.8 %) in group B (difference 1.9 (95 % CI -6.19 to 9.99; P = 0.997). The present study was unable to prove that the drain was useful in elective, uncomplicated LC.


Magnesiate-Utilized/Benzyne-Mediated Approach to Indenopyridones from 2-Pyridones: An Attempt To Synthesize the Indenopyridine Core of Haouamine.
An efficient, short-staged synthesis of cis-fused indeno[2,1-b]- and indeno[1,2-c]pyridin-2-ones, starting from 2-pyridones, using magnesiates of type R3MgLi as nucleophilic and deprotonation agents, mediated by benzyne generated in situ, under optimized conditions, is described. Following the developed protocol, rare C4a-arylsubstituted indeno[2,1-b]pyridones, resembling the core of haouamine, were obtained. The protocol offering the one-pot synthesis directly from 2-pyridone is also described.


Distribution of capsaicin-sensitive substance P- and calcitonin gene-related peptide-immunoreactive nerves in bovine respiratory tract.
The distribution of nerve fibers immunoreactive for substance P (SP) and calcitonin gene-related peptide (CGRP) was examined by means of immunohistochemical methods in the respiratory tract from nose to lung of normal and capsaicin-treated cattle. SP- and CGRP-immunoreactive (IR) nerve fibers with varicosities were detected in all portions. They were more numerous in calves than in cows. They were abundant in the nasal and laryngeal mucosae and tracheal bronchus, and few in number in the lung. SP- and CGRP-IR nerve fibers were mainly seen in the epithelium, in connective tissue beneath the epithelium and around blood vessels, and in the glands throughout the respiratory tract. In contrast, SP- and CGRP-IR nerve fibers were sparse in the smooth muscle layer. Capsaicin treatment of neonates caused a remarkable reduction in the number of SP- and CGRP-IR nerve fibers in the respiratory tract of calves. Double immunofluorescence experiments showed the colocalization of SP and CGRP in most of the nerve fibers. The present findings suggest that SP- and CGRP-IR nerve fibers are involved in the regulation of the bovine respiratory tract, and that capsaicin-sensitive SP- and CGRP-IR nerve fibers are sensory neurons of the bovine respiratory tract.


Differential regulation of MMP-1/9 and TIMP-1 secretion in human monocytic cells in response to Mycobacterium tuberculosis.
In tuberculosis, matrix metalloproteinase (MMP) secretion is involved in leukocyte migration to sites of infection but in excess may contribute to tissue destruction. We demonstrate that human monocytic THP-1 cells and primary monocytes secrete MMP-1 (52 kD collagenase) when phagocytosing live, virulent M. tuberculosis but not inert latex. The magnitude of MMP-1 secretion was approximately 10-fold less when compared to MMP-9 (92 kD gelatinase) secretion. MMP-1 secretion was also relatively delayed (detected at 24 h vs. 4 h). M. tuberculosis, zymosan or latex stimulate similar TIMP-1 secretion within 8 h and increasing over 24 h. MMP-1/9 secretion was decreased by inhibitors of protein kinase (PK) C, PKA or tyrosine kinases (PTK) in a concentration-dependent manner. In contrast, TIMP-1 secretion was not affected by PKC or PTK blockade and only somewhat reduced by high level PKA inhibition. In summary, M. tuberculosis-infected monocytes secrete MMP-1 at lower concentrations than MMP-9 and such MMP secretion is regulated by multiple upstream signalling pathways which do not control TIMP-1 secretion. Divergent effects of i on MMP and TIMP secretion from monocytes may be important in influencing matrix degradation in vivo.


Proteomic analysis of a model unicellular green alga, Chlamydomonas reinhardtii, during short-term exposure to irradiance stress reveals significant down regulation of several heat-shock proteins.
Oxygenic photosynthetic organisms often suffer from excessive irradiance, which cause harmful effects to the chloroplast proteins and lipids. Photoprotection and the photosystem II repair processes are the mechanisms that plants deploy to counteract the drastic effects from irradiance stress. Although the protective and repair mechanisms seemed to be similar in most plants, many species do confer different level of tolerance toward high light. Such diversity may originate from differences at the molecular level, i.e., perception of the light stress, signal transduction and expression of stress responsive genes. Comprehensive analysis of overall changes in the total pool of proteins in an organism can be performed using a proteomic approach. In this study, we employed 2-DE/LC-MS/MS-based comparative proteomic approach to analyze total proteins of the light sensitive model unicellular green alga Chlamydomonas reinhardtii in response to excessive irradiance. Results showed that among all the differentially expressed proteins, several heat-shock proteins and molecular chaperones were surprisingly down-regulated after 3-6 h of high light exposure. Discussions were made on the possible involvement of such down regulation and the light sensitive nature of this model alga.


Measuring green development level at a regional scale: framework, model, and application.
In this study, we propose and construct a novel model that measures regional green development level based on the "three-circle" conceptual framework for green development. Using Jiangsu Province in eastern China as a case study, the spatial-temporal characteristics and dynamics of the green development level from 2000 to 2020 were evaluated using a multi-source dataset at the grid-cell level. Our results show that (1) the analytical hierarchy process-based model proposed herein has higher reliability in terms of the development level measurement than principal component analysis and the entropy weight method. In addition, the average score of green development in the study area was approximately 0.53. Spatially, the green development level in the eastern coastal areas of the study area was found to be generally higher than in other regions, while that in southwestern regions is relatively low. In terms of sub-regions, the green development level scores of the study area have been ranked as follows: middle Jiangsu > southern Jiangsu > northern Jiangsu. (2) It was observed that the gravity center of the green development level can be divided into three stages during the study, with a whole had shifted to the north. (3) For most cities in Jiangsu, the green development level initially increased at first, then declined, and then increased again. (4) In the future, the green development level of Jiangsu Province should pay more attention to promoting regional coordinated development and relationships between society and the environment under rapid economic development.


Evidence-based surgery: The obstacles and solutions.
Surgeons are often accused of lagging behind their medical colleagues in embracing evidence based medicine and utilizing new research tools to conducting high quality randomized controlled trials. Although there has been a noticeable improvement in the quantity and quality of high quality studies in surgical journals, the widespread practice of evidence based surgery is still poor. Unlike evidence based medicine, the practice of evidence based surgery is hampered by inherent problems and obstacles. This article reviews these difficulties and the limitations of randomized controlled trials in surgical practice. It also outlines some solutions that may help remedy this ongoing problem.


A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population.
To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 ( ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(-273)C ( P=0.0074), C(-297)T ( P=0.0195), and IMS-JST071749 ( P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(-273)C genotype was influential in another set of subjects ( P=0.0310, n=743). However, the distribution of the ABCA1 G(-273)C genotype in subjects with MI ( n=598) was not different from that in the control population ( n=801). These results indicate that ABCA1 G(-273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.


Personal digital assistants in health care: experienced clinicians in the palm of your hand?
Physicians and other health-care professionals are rapidly adopting personal digital assistants (PDA). Palm pilots and other hand-held computers are also increasingly popular among medical students. PDAs can be used for medical student education and physician training, daily clinical practice, and research. PDAs and their increasing integration with information technology in hospitals could change the way health care is delivered in the future. But despite the increasing use of PDAs, evidence from well-designed research studies is still needed to show how much these devices can improve the quality of care, save patients' lives, and ultimately reduce health-care expenses. In this Review of PDA use in health care, the operating systems, basic functionality, security and safety, limitations, and future implications of PDAs are examined. A personal perspective and an introduction to medical PDA applications, software, guidelines, and programmes for health-care professionals is also provided.


Polylekithum percai n. sp. (Trematoda: Allocreadiidae) from Percichthys trucha (Perciformes: Percichthydae) in Patagonia, Argentina, and a redescription of Homalometron papilliferum (Szidat, 1956) n. comb.
Two species of Digenea are recorded from the intestine of Percichthys trucha (Percichthydae) from Patagonian water bodies. Polylekithum percai n. sp. (Allocreadiidae) is distinguished by its body size, the relative size of the suckers, the anterior extension of the vitelline fields, the number of eggs in the uterus and the different species of fish host from the two previously described species of Polylekithum. Homalometron (= Austrocreadium) papilliferum (Szidat, 1956) n. comb. is redescribed. Due to its spined tegument and the absence of a cirrus-sac, this species is considered a member of the family Apocreadiidae.


The kinetics of thymine dimer excision in ultraviolet-irradiated human cells.
We have investigated the kinetics of the loss of thymine dimers from the acid-insoluble fraction of several ultraviolet (UV)-irradiated cultured human cell lines. Our results show that UV fluences between 10 and 40 J/m2 produce an average of 21-85 x 10(5) thymine dimers per cell and an eventual maximal loss per cell of 12-20 x 10(5) thymine dimers. The time for half-maximal loss of dimers ranged from 12-22 h after UV irradiation. In contrast, the time for half-maximal repair synthesis of DNA measured by autoradiography was 4.5 h. This figure agrees well with reported half-maximal repair synthesis times, which range from 0.5 to 3.6 h based on our analysis. The discrepancy in the kinetics of the loss of thymine dimers from DNA and repair synthesis is discussed in terms of possible molecular mechanisms of thymine dimer excision in vivo and in terms of possible experimental artifacts.


The incidence of physeal fractures in the lower limb and the frequency of premature physeal closure: a cohort study of 236 patients.
Physeal fractures represent 15-20% of all pediatric fractures and may lead to premature physeal closure (PPC). The aim of our study was to determine the incidence rates of physeal fractures in the lower limb and the proportion of PPC that lead to limb length discrepancy (LLD), and/or angular deformity (AD). This retrospective study included 236 consecutive children with physeal fracture in the tibia, distal femur, or distal fibula. We estimated incidence rates and reviewed medical records and radiographs to obtain information regarding the development of PPC leading to LLD and AD. Of the 236 children, 100 had planned growth control or were referred for growth control due to symptoms of PPC. The total incidence rate was 35 (95% CI 30-39) per 100,000 person-years, with 1.2 (CI 0.5-23) for distal femur, 5.7 (CI 3.1-7.8) for proximal tibia, 14 (CI 11-17) for distal tibia, and 14 (CI 11-17) for distal fibula. The overall prevalence of PPC was 9.7% (CI 6.3-14), while the prevalence was 38% (CI 8.5-76) for distal femur, 15% (CI 5.9-31) for proximal tibia, 14% (CI 7.4--22) for distal tibia, and 1.1% (CI 0.3--59) for distal fibula. We found a significant higher hazard of PPC in fractures with ≥ 3 mm displacement (hazard ratio: 12, CI 1.5-97). 10% of children with physeal fractures developed PPC that led to LLD or AD. The highest hazard ratio was in children who had an initial fracture displacement. This study highlights the importance of routine and uniform growth evaluation after a physeal fracture.


Effect of Calcium ion on synaptotagmin-like protein during pre-fusion of vesicle for exocytosis in blood-brain barrier.
Calcium signaling and membrane fusion play key roles in exocytosis of drug-containing vesicles through the blood-brain barrier (BBB). Identifying the role of synaptotagmin-like protein4-a (Slp4-a) in the presence of Ca2+ ions, at the pre-fusion stage of a vesicle with the basolateral membrane of endothelial cell, can reveal brain drug transportation across BBB. We utilized molecular dynamics (MD) simulations with a coarse-grained PACE force field to investigate the behaviors of Slp4-a with vesicular and endothelial membranes at the pre-fusion stage of exocytosis since all-atom MD simulation or experiments are more time-consuming and expensive to capture these behaviors. The Slp4-a pulls lipid membranes (vesicular and endothelial) into close proximity and disorganizes lipid arrangement at contact points, which are predictors for initiation of fusion. Our MD results also indicate that Slp4-a needs Ca2+ to bind with weakly-charged POPE lipids (phosphatidylethanolamine). Slp4-a is an important trigger for membrane fusion in BBB exocytosis. It binds to lipid membranes at multiple binding sites and triggers membrane disruption for fusion in calcium-dependent case. Understanding the prefusion process of the vesicle will help to design better drug delivery mechanisms to the brain through formidable BBB.


An exploration of participants' experience of an intensive care nursing transition to specialty practice program.
Transition to specialty practice programs were developed to support, educate and facilitate recruitment and retention of nurses in specialised areas of practice. The intensive care nursing transition to specialty practice program in this study was implemented in 2000. To date, in Australia there are no published studies which focus on intensive care nursing transition to specialty practice programs. The study aimed to explore the effects of an intensive care nursing transition to specialty practice program offered in two intensive care units in a single Australian health service. A cross-sectional survey design was used. Quantitative data were collected from nurses who participated in the transition to specialty practice program from 2005 to 2015 using an anonymous online survey. Summary statistics and Chi-square tests were used to analyse the data. The response rate was 51.8% (n=86). Most of the transition to specialty practice program participants had medical nursing experience (n=35, 40.7%) or surgical nursing experience (n=35, 40.7%) prior to enrolling into the program. More than half (n=46, 53.5%) of the participants had worked in the intensive care units for more than two years post program. The majority of the participants (n=60, 69.8%) undertook post graduate education after the transition to specialty practice program. Significant numbers of experienced nurses undertook transition to specialty practice program into intensive care and majority of the participants reported positive results of the program.


Beyond the Effects of Comprehensive Sexuality Education: The Significant Prospective Effects of Youth Assets on Contraceptive Behaviors.
The purpose of the study was to prospectively determine if youth assets were significantly associated with contraception use after accounting for the effects of youths' exposure to comprehensive sexuality education programming. Prospective associations between youth asset scores, comprehensive sexuality education topics received, type of contraceptive used, and consistent contraceptive use were analyzed using multinomial and binomial logistic regression in a sample of 757 sexually active youth. Higher youth asset scores were associated with condom use (adjusted odds ratio [AOR] = 1.51, 95% CI = 1.01-2.28), hormonal birth control use (AOR = 2.71, 95% CI = 1.69-4.35), dual method use (AOR = 2.35, 95% CI = 1.44-3.82), and consistent contraceptive use (AOR = 1.97, 95% CI = 1.38-2.82). After controlling for youths' experience with comprehensive sexuality education, higher youth asset scores remained a significant predictor of hormonal birth control use (AOR = 2.09, 95% CI = 1.28-3.42), dual method use (AOR = 2.58, 95% CI = 1.61-4.15), and consistent contraceptive use (AOR = 1.95, 95% CI = 1.36-2.80). Youth serving organizations that are interested in preventing teen pregnancy should consider widespread implementation of evidence-based youth development programs that focus on building and strengthening specific youth assets.


Hidden octupole order in URu₂Si₂.
We propose that the hidden order in URu₂Si₂ is an incommensurate octupole order, which is derived from a spin-1 XXZ model with XX octupole and Z dipole interactions based on the singlet-doublet crystal-field level scheme. The octupole moments break time-reversal invariance and give rise to finite hyperfine fields on the nuclei of the ligand Si and Ru ions. In order for the hyperfine fields to be observed as a nuclear magnetic resonance (NMR) linewidth, the order must be incommensurate, with the ordering vector determined so as to account for the ²⁹Si NMR linewidth data quantitatively.


Resveratrol exerts anxiolytic-like effects through anti-inflammatory and antioxidant activities in rats exposed to chronic social isolation.
Emerging evidence has confirmed resveratrol's (RES) antioxidant, anti-inflammatory, and antidepressant effects. The beneficial effects of RES were confirmed for several emotional and cognitive deficits. This research aimed to assess the impacts of RES on behavior and hippocampal levels of anti-inflammatory and pro-inflammatory factors in rats exposed to chronic social isolation (SI) stress, which is known to induce mental disorders such as depressive-like behavior. The animals were treated by RES (20, 40, or 80 mg/kg/intraperitoneally) for 28 days following a 28-day exposure to stress. Behavioral tests, including the forced swim test (FST), open-field test (OFT), tail suspension test (TST), and sucrose preference test (SPT), assessed depressive symptoms. Finally, the animals were sacrificed, and molecular studies (qPCR and ELISA) were performed. Exposure of animals to SI dramatically increased the immobility of animals in TST and FST, enhanced the time spent in the open-field peripheral zone of the OFT, and reduced the sucrose preference rate. In addition, SI increased serum levels of corticosterone and hippocampal content of MDA, whereas it reduced hippocampal SOD and CAT activities. Moreover, SI upregulated the expression of IL-10, IL-18, and IL-1β and downregulated the expression of TGF-β in the hippocampus. RES treatment (40 & 80 mg/kg) significantly improved the behavioral alterations through the modulation of neuroinflammation and oxidative stress. The 20 mg/kg RES dose was inefficient for treating SI-induced depressive-like behavior. These results indicated that RES attenuated depressive-like behavior in prolonged stressed animals. These properties might be associated with RES-mediated improvements in serum corticosterone and hippocampal inflammatory and oxidative stress biomarkers.


Ornithine alpha-ketoglutarate counteracts thymus involution and glutamine depletion in endotoxemic rats.
This work studied the action of ornithine a-ketoglutarate (OKG) supplementation in an experimental model of endotoxemia in the rat. Male Wistar rats were injected intraperitoneally with lipopolysaccharide (LPS) from Escherichia coli (0127:B8). They were fasted for 24 h, then refed for 48 h with an enteral diet supplemented with either OKG (66 mg N x kg(-1) x d(-1)) or glycine, isonitrogenous to the OKG group. A control (sham) group was also studied. LPS treatment induced a decrease in thymus and muscle weights compared to controls, and a decrease in glutamine and arginine concentrations in the anterior tibialis muscle. Supplementation with OKG restored thymus weight and muscle arginine level and increased muscle glutamine concentration, when compared to controls. We conclude that OKG counteracts the thymic involution that occurs with endotoxemia, and restores the muscular content of glutamine and arginine, both of which are involved in the regulation of immune function.


The chromosome 1;11 translocation provides the best evidence supporting genetic etiology for schizophrenia and bipolar affective disorders.
Genetics is assumed to cause susceptibility to psychosis, but no major locus has been identified. These disorders cosegregate with a chromosome 1;11 translocation in a Scottish pedigree where 50% of the carriers are diseased. A genetic model originally proposed to explain the basis of these illnesses predicts such an outcome.


Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide.
Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to interact with neuronal transmission mediated by glutamate, gamma-aminobutyric acid (GABA) and glycine. The goal of this study was to test the interaction of bilobalide with glycine in assays of neuroprotection. In rat hippocampal slices exposed to N-methyl-D-aspartate (NMDA), release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of bilobalide (10 microM). Glycine (10-100 microM) antagonized the inhibitory action of bilobalide in this assay. In a second assay of excitotoxicity, we measured tissue water content as an indicator of cytotoxic edema formation in hippocampal slices which were exposed to NMDA. In this assay, edema formation was suppressed by bilobalide but bilobalide's action was attenuated in the presence of glycine and of D-serine (100 microM each). To investigate bilobalide's interaction with glycine receptors directly, we determined 36chloride flux in rat cortico-hippocampal synaptoneurosomes. Glycine (100 microM) was inactive in this assay indicating an absence of functional glycine-A receptors in this preparation. [3H]Glycine was used to assess binding at the glycine binding site of the NMDA receptor but bilobalide was found to be inactive in this assay. Finally, [3H]glycine release was monitored in hippocampal slices exposed to oxygen-glucose deprivation. In this model, glycine release was induced by ischemia, an effect that was strongly reduced by bilobalide. We conclude that bilobalide does not interact with glycine receptors in neurochemical assays but it significantly reduces the release of glycine under ischemic conditions. This effect likely contributes to bilobalide's neuroprotective effects in assays of excitotoxicity and ischemia.