Hepatitis C Virus Nonstructural 5A Protein (HCV-NS5A) Inhibits Hepatocyte Apoptosis through the NF-κb/miR-503/bcl-2 Pathway.
The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor (TNF)-α. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship. Chromatin immunoprecipitation was used to identify the combination of NF-κB and miR-503. We found that overexpression of NS5A inhibited TNF-αinduced hepatocellular apoptosis via regulating miR-503 expression. The cell viability of the TNF-α induced Hep-mock cells was significantly less than the viability of the TNF-α induced Hep-NS5A cells, which demonstrates that NS5A inhibited TNF-α-induced HepG2 cell apoptosis. Under TNF-α treatment, miR-503 expression was decreased and cell viability and B-cell lymphoma 2 (bcl-2) expression were increased in the Hep-NS5A cells. Moreover, the luciferase reporter gene experiment verified that bcl-2 was a direct target of miR-503, NS5A inhibited TNF-α-induced NF-κB activation and NF-κB regulated miR-503 transcription by combining with the miR-503 promoter. After the Hep-NS5A cells were transfected with miR-503 mimics, the data indicated that the mimics could reverse TNF-α-induced cell apoptosis and blc-2 expression. Collectively, our findings suggest a possible molecular mechanism that may contribute to HCV treatment in which NS5A inhibits NF-κB activation to decrease miR-503 expression and increase bcl-2 expression, which leads to a decrease in hepatocellular apoptosis.


Cerebral hypoperfusion-assisted intra-arterial deposition of liposomes in normal and glioma-bearing rats.
Optimizing liposomal vehicles for targeted delivery to the brain has important implications for the treatment of brain tumors. The promise of efficient, brain-specific delivery of chemotherapeutic compounds via liposomal vehicles has yet to be achieved in clinical practice. Intra-arterial injection of specially designed liposomes may facilitate efficient delivery to the brain and to gliomas. To test the hypothesis that cationic liposomes may be effectively delivered to both normal and glioma-bearing brain tissue utilizing a strategy of intra-arterial injection during transient cerebral hypoperfusion. Cationic, anionic, and neutral liposomes were separately injected via the internal carotid artery of healthy rats during transient cerebral hypoperfusion. Rats bearing C6 gliomas were similarly injected with cationic liposomes. Liposomes were loaded with DilC18(5) dye whose concentrations can be measured by light absorbance and fluorescence methods. After intra-arterial injection, a robust uptake of cationic in comparison with anionic and neutral liposomes into brain parenchyma was observed by diffuse reflectance spectroscopy. Postmortem multispectral fluorescence imaging revealed that liposomal cationic charge was associated with more efficient delivery to the brain. Cationic liposomes were also readily observed within glioma tissue after intra-arterial injection. However, over time, cationic liposomes were retained longer and at higher concentrations in the surrounding, peritumoral brain than in the tumor core. This study demonstrates the feasibility of cationic liposome delivery to brain and glioma tissue after intra-arterial injection. Highly cationic liposomes directly delivered to the brain via an intracarotid route may represent an effective method for delivering antiglioma agents.


A new approach for analyzing cellular infiltration during allergic airway inflammation.
A mouse model for allergic airway inflammation involving ovalbumin (OVA) sensitization and challenge has been developed that reproduces hallmark features of human asthma and has provided valuable insight into the mechanisms by which this disease occurs. Cellular infiltrate in lungs of mice used in this model have conventionally been evaluated using histological examination of tissue sections and light microscopic analysis of lung lavage samples. As an alternative or complementary approach for characterizing cellular infiltrate, we developed a multicolor fluorescence-activated cell sorter (FACS) method involving the simultaneous detection of seven different markers on lung cell suspensions: CD4, CD8, B220, CD11b, Gr-1, CD49b, and FcepsilonRI. Only some of these cell types increased in OVA-challenged mice compared to PBS controls, including the CD4(+), B220(+), CD11b(+), and FcepsilonRI(+) groups. We also examined subpopulations of cells for coexpression of these markers and dissected heterogeneous populations as further evaluation procedures to characterize the cellular infiltrate resulting from OVA challenge. Finally, we combined FACS with real-time PCR to analyze certain cell types in terms of mRNA levels for factors involved in asthma, including GATA-3 and IL-1beta. Overall, these FACS-based techniques provide a powerful approach for analyzing cellular profiles in lung tissue from mice used in the mouse model of asthma and may also prove valuable in evaluating cellular infiltrates for other models of inflammation and immune responses.


Highly tumoricidal efficiency of non-oxidized MXene-Ti3C2Tx quantum dots on human uveal melanoma.
Uveal melanoma (UM) is a highly malignant intraocular tumor with poor prognosis. Current topical ophthalmic therapies purpose to conserve the eye and useful vision. Due to the risks and limited clinical benefits, the topical treatments of UM remain challenging and complex. In this study, newly developed non-oxidized MXene-Ti3C2Tx quantum dots (NMQDs-Ti3C2Tx) are proposed for UM treatment. Surprisingly, NMQDs-Ti3C2Tx shows significant tumor-killing effects on UM cells in a dose-dependent manner and causes severe necrosis near the injection site on the xenograft UM tumor model. Moreover, NMQDs-Ti3C2Tx exhibits excellent biocompatibility with normal retina pigment epithelium (RPE) cells and does not cause any damage in C57BL/6 mice eyes. Mechanistically, NMQDs-Ti3C2Tx inhibits the proliferation, invasion, and migration of UM cells via its desirable reactive oxygen species (ROS) generation ability, which causes lipid peroxidation and mitophagy, triggering cell ferroptosis. Furthermore, NMQDs-Ti3C2Tx is detected accumulating in autolysosomes which exacerbates cell death. This work provides new light on the topical treatment of UM.


Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study.
AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. NCT00096824.


Incomplete IgG avidity maturation after seasonal coronavirus infections.
In classical viral infections, the avidity of immunoglobulin G (IgG) is low during acute infection and high a few months later. As recently reported, SARS-CoV-2 infections are not following this scheme, but they are rather characterized by incomplete avidity maturation. This study was performed to clarify whether infection with seasonal coronaviruses also leads to incomplete avidity maturation. The avidity of IgG toward the nucleoprotein (NP) of the seasonal coronaviruses 229E, NL63, OC43, HKU1 and of SARS-CoV-2 was determined in the sera from 88 healthy, SARS-CoV-2-negative subjects and in the sera from 70 COVID-19 outpatients, using the recomLine SARS-CoV-2 assay with recombinant antigens. In the sera from SARS-CoV-2-negative subjects, incomplete avidity maturation (persistent low and intermediate avidity indices) was the lowest for infections with the alpha-coronaviruses 229E (33.3%) and NL63 (61.3%), and the highest for the beta-coronaviruses OC43 (77.5%) and HKU1 (71.4%). In the sera from COVID-19 patients, the degree of incomplete avidity maturation of IgG toward NP of 223E, OC43, and HKU1 was not significantly different from that found in SARS-CoV-2-negative subjects, but a significant increase in avidity was observed for IgG toward NP of NL63. Though there was no cross-reaction between SARS-CoV-2 and seasonal coronaviruses, higher concentrations of IgG directed toward seasonal coronaviruses seemed to indirectly increase avidity maturation of IgG directed toward SARS-CoV-2. Our data show that incomplete IgG avidity maturation represents a characteristic consequence of coronavirus infections. This raises problems for the serological differentiation between acute and past infections and may be important for the biology of coronaviruses.


Ion channels in Madin-Darby canine kidney cells.
Ion channels in Madin-Darby canine kidney cells serve transepithelial chloride transport and probably cell volume regulation. Three distinct potassium channels and one anion channel have been revealed by patch clamp studies in Madin-Darby canine kidney cells. The potassium channels are activated by an increase in intracellular calcium activity. A number of hormones activate the potassium channels by an increase in intracellular calcium activity. However, under certain conditions the hormones hyperpolarize the cell membrane without increasing intracellular calcium activity sufficiently to activate the calcium-sensitive potassium channels. Thus, the hormones may activate potassium channels via another, as yet undefined, intracellular mechanism. The anion channel is stimulated by cAMP. Another factor modifying channel activity is cell volume: cell swelling leads probably to subsequent activation of potassium and anion channels. The net result is a variable transient hyperpolarization followed by a sustained depolarization of the cell membrane.


[Expression of human micro-dystrophin gene after retrovirus infection in mdx mice bone marrow-derived mesenchymal stem cells].
To construct the retroviral vector containing human micro-dystrophin gene and detect the expression of human micro-dystrophin in mdx mice bone marrow-derived mesenchymal stem cells (MSCs) after retrovirus infection. Retroviral vector for micro-dystrophin gene was constructed and transferred into the packing cell PA317 mediated by Lipofectamine 2000. The retroviral supernatant containing the target genes were subsequently used to infect mdx mice MSCs. Micro-dystrophin expression was examined by methods of immunofluorescence staining and reverse transcriptase-polymerase chain reaction. Micro-dystrophin retroviral vector was successfully constructed and transferred into PA317 cells, and 48 h after infection with the recombinant retrovirus in mdx mice MSCs, 319 bp fragment could be detected by electrophoresis in the RT-PCR products. The red particles could be detected in some infected mdx mice MSCs with immunofluorescence staining. CONCLUSION mdx mice MSCs infected with retrovirus containing micro-dystrophin gene can express micro-dystrophin protein.


Perceiving prosody from the face and voice: distinguishing statements from echoic questions in English.
We examined the processing of potential auditory and visual cues that differentiate statements from echoic questions. In Experiment 1, four natural speech statement-question pairs were identified by participants, and then analyzed to determine which characteristics were ecologically valid. These characteristics were tested in subsequent experiments to determine if they were also functionally valid. In Experiment 2, the characteristics of the most discriminable utterance pair were successfully extended to the other utterance pairs. For Experiment 3, an auditory continuum (varying in F0, amplitude, duration) was crossed with a visual continuum (varying in eyebrow raise, head tilt), using synthetic speech and a computer-animated head. Participants judged five levels along each of these two speech continua between a prototypical statement and prototypical question, in an expanded factorial design. Experiments 4 and 5 were unable to appreciably enhance the weak visual effect relative to the strong auditory effect (from Experiment 3). Overall, we found that both auditory and visual cues reliably conveyed statement and question intonation, were successfully synthesized, and generalized to other utterances. However, the weak visual effect relative to the robustly strong auditory effect precluded optimal integration and conclusive examination of information processing through model-fitting.


Potential applications of fish oils rich in n-3 fatty acids in the palliative treatment of advanced pancreatic cancer.
The palliative treatment of patients with advanced pancreatic cancer (APC) has undergone little advancement in the last 15 years. Novel therapies that have been investigated to extend survival have shown little benefit over existing chemotherapy regimens. Patients with APC often experience significant weight loss, which is one of the primary factors involved in declining quality of life. Recently, the ability of n-3 fatty acid rich oral preparations to attenuate or reverse tumour-related weight loss has been investigated in this patient group with encouraging results. Laboratory investigation has also yielded promising results suggesting a potential direct tumouricidal effect of n-3 fatty acids as well as the putative potentiation of existing chemotherapy regimes. The present review aims to examine the potential applications of fish oils rich in n-3 fatty acids in patients with APC, present a selection of the studies carried out to date and outline avenues of possible further clinical investigation.


In-vivo impact of common cosmetic preservative systems in full formulation on the skin microbiome.
Preservatives play an essentially role in ensuring that cosmetic formulations remain safe for use via control of microbial contamination. Commonly used preservatives include organic acids, alcohols and phenols and these play an essential role in controlling the growth of bacteria, fungi and moulds in substrates that can potentially act as a rich food source for microbial contaminants. Whilst the activity of these compounds is clear, both in vitro and in formulation, little information exists on the potential impact that common preservative systems, in full formulation, have on the skin's resident microbiome. Dysbiosis of the skin's microbiome has been associated with a number of cosmetic conditions but there currently are no in vivo studies investigating the potential for preservative ingredients, when included in personal care formulations under normal use conditions, to impact the cutaneous microbiome. Here we present an analysis of four in vivo studies that examine the impact of different preservation systems in full formulation, in different products formats, with varying durations of application. This work demonstrates that despite the antimicrobial efficacy of the preservatives in vitro, the skin microbiome is not impacted by preservative containing products in vivo.


Lipoprotein(a) in patients who have non-insulin-dependent diabetes with and without coronary artery disease.
To determine whether the level of lipoprotein(a) [Lp(a)] contributes to an increased risk of coronary artery disease (CAD) in patients with non-insulin-dependent diabetes mellitus (NIDDM). We prospectively evaluated established cardiovascular risk factors, metabolic control, and Lp(a) levels in 53 men with NIDDM and CAD and compared these variables in 42 male patients with NIDDM but without CAD. The groups were comparable for age, diabetes control, treatment and duration of diabetes, obesity, and other cardiac risk factors. Lp(a) levels did not differ between the groups (12.2 versus 12.4 mg/dL in those with and without CAD, respectively) and were unrelated to age, duration of diabetes, diabetes control, obesity, smoking, hypertension, urinary albumin, cholesterol, triglycerides, or high-density lipoprotein cholesterol. Patients with retinopathy had a higher Lp(a) concentration than did those without retinopathy (24.9 +/- 6.0 versus 10.1 +/- 1.5 mg/dL; P = 0.01). A significant correlation existed between Lp(a) and low-density lipoprotein cholesterol concentrations (P = 0.01). Routine measurement of Lp(a) level in patients with NIDDM does not seem warranted because no association was found between Lp(a) concentration and CAD in this study population.


Redirected activity of human antitumor chimeric immune receptors is governed by antigen and receptor expression levels and affinity of interaction.
Novel Ab-based immunotherapeutic strategies have exploited T-cell receptor-like chimeric immune receptors (CIR) expressed on the surface of transduced human peripheral blood mononuclear cell (PBMC) to redirect potent non-major histocompatibility complex-dependent cytotoxicity to tumor cells expressing a tumor-associated antigens. We transduced human PBMC with 2 fully human CIRs that trigger through the zeta-chain of CD3 and contain either one of two human scFv specific for the same epitope on the extracellular domain of HER2 but with distinctly different affinities (KD 1616 and 1 nM) for this antigen. Potent direct CIR-mediated killing and in vitro tumor growth inhibition mediated by transduced PBMC were observed against targets expressing different levels of HER2. High-affinity CIR showed stronger ability to bind Ag and retain binding than low-affinity CIR. When lytic potential of the 2 CIRs was evaluated, their efficiency was comparable under conditions of high CIR and Ag expression, whereas low-affinity CIR was more efficient than high-affinity CIR in conditions of limiting Ag and CIR expression levels. When tumor growth inhibition was evaluated, Ag and CIR levels, rather than CIR affinity appeared relevant. Ag-driven CIR activation resulted in the production of soluble factors mediating efficient bystander effect. By carefully defining CIR surface expression and increasing affinity for a specific target antigen, it may be possible to selectively exclude CIR-mediated activity against targets expressing low levels of antigen, as normal cells. On the contrary, low antigen-expressing tumor variants could be eliminated by decreasing CIR affinity. Tuning CIR expression and affinity might help in discriminating different biologic contexts.


Amino acid sequence of bovine cardiac troponin I.
Troponin I (TnI) is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium sensitivity to striated muscle actomyosin ATPase activity. We have determined the amino acid sequence of TnI from adult bovine cardiac muscle. This protein is a single polypeptide chain of 211 amino acids with an acetylated amino terminus, a calculated molecular weight of 23,975, and a net charge of +17 at neutral pH. There was no evidence for heterogeneity of the sequence. Comparison with other available TnI sequences shows an amino-terminal extension of 27-33 residues which is present in cardiac but not skeletal TnI. The remainder of the polypeptide is common to both cardiac and skeletal TnI. In the amino-terminal half of the common polypeptide, only 29% of the residues are invariant in all sequences. The carboxyl-terminal half (residues 124-210) is much more highly conserved, with 66% invariant residues. Bovine cardiac TnI and rabbit cardiac TnI are very similar in sequence: only 12 of 26 residues are identical in the amino-terminal segments, but the remaining residues of the proteins are 97% identical.


PELVIC ACTINOMYCOSIS MIMICKING A LOCALLY ADVANCED PELVIC MALIGNANCY--CASE REPORT.
We present the case of a former user of an intrauterine contraceptive device (IUD) for 10 years, diagnosed with a bulky, fixed pelvic tumor involving the internal genital organs and the recto sigmoid, causing luminal narrowing of the rectum, interpreted as locally advanced pelvic malignancy, probably of genital origin. Intraoperatively, a high index of suspicion made us collect a sample from the fibrous wall of the tumor mass, large Actinomyces colonies were thus identified. Surgery consisted in debridement, removal of a small amount of pus and appendectomy, thus avoiding a mutilating and useless surgery. Specific antibiotic therapy was administered for 3 months, with favorable postoperative and long-term outcomes. Pelvic actinomycosis should always be considered in the differential diagnosis of pelvic tumors in women using an IUD. The association of long-term antibiotic treatment is essential to eradicate the infection and prevent relapses.


Math Anxiety Is Related to Some, but Not All, Experiences with Math.
Math anxiety has been defined as unpleasant feelings of tension and anxiety that hinder the ability to deal with numbers and math in a variety of situations. Although many studies have looked at situational and demographic factors associated with math anxiety, little research has looked at the self-reported experiences with math that are associated with math anxiety. The present study used a mixed-methods design and surveyed 131 undergraduate students about their experiences with math through elementary school, junior high, and high school, while also assessing math anxiety, general anxiety, and test anxiety. Some reported experiences (e.g., support in high school, giving students plenty of examples) were significantly related to the level of math anxiety, even after controlling for general and test anxiety, but many other factors originally thought to be related to math anxiety did not demonstrate a relation in this study. Overall, this study addresses a gap in the literature and provides some suggestive specifics of the kinds of past experiences that are related to math anxiety and those that are not.


Antioxidant supplementation and breast cancer prognosis in postmenopausal women undergoing chemotherapy and radiation therapy.
There is a paucity of information on the prevalence of dietary supplement use in breast cancer survivors. Only a few studies have examined the impact of dietary supplements, particularly antioxidants, on breast cancer prognosis and the results are inconclusive. We examined pre- and postdiagnosis use of supplements in postmenopausal breast cancer survivors in Germany and investigated associations between postdiagnosis use of antioxidants and other supplements, and prognosis (total and breast cancer mortality, and recurrence-free survival) both overall and in women who received chemotherapy and radiation therapy. Data from 2223 postmenopausal women diagnosed with nonmetastatic breast cancer from the population-based Mamma Carcinoma Risk Factor Investigation (MARIE) study were used. Women were interviewed at recruitment in 2002-2005 and again in 2009 and followed-up until 30 June 2015. Multivariate Cox regression analysis was used to estimate HRs and corresponding 95% CIs. Pre- and postdiagnosis supplement use was reported by 36% and 45% of the women, respectively. There were 240 deaths (134 from breast cancer) and 200 breast cancer recurrences after a median follow-up time of 6.0 y after the 2009 re-interview. After adjusting for relevant confounders, concurrent antioxidant use with chemotherapy or radiation therapy among 1940 women was associated with increased risk of total mortality (HR: 1.64; 95% CI: 1.01, 2.66) and worsened recurrence-free survival (HR: 1.84; 95% CI: 1.26, 2.68). Overall postdiagnosis supplement use was not associated with breast cancer prognosis. Antioxidant use during chemotherapy or radiation therapy was associated with worsened breast cancer prognosis in postmenopausal women. There was no overall association between postdiagnosis supplement use and breast cancer prognosis. Results from our study align with the current recommendation to possibly avoid the use of antioxidants during chemotherapy or radiation therapy.


The production of the enzyme dextransucrase using nonaerated fermentation techniques.
High yields of the enzyme dextransucrase have been produced repeatedly by fed-batch fermentation techniques. Activities in excess of 21.9 U/cm(3) have been obtained by culturing Leuconostoc mesenteroides NRRL B-512(F) under nonaerated fed-batch fermentation conditions. Aerobic fermentations carried out under identical conditions have consistently produced enzyme of less than 17 U/cm(3), but with no difference in the final cell concentration in the broth. Different types of yeast extract have been found to have significant effect on the final cell concentration and more especially on the enzyme activity with enzyme yields varying by as much as 50% when different types of yeast extracts were used.


Diversity in and evidence for selection on the mitochondrial genome of Phytophthora infestans.
Two extant nomenclature systems were reconciled to relate six mitochondrial DNA (mtDNA) haplotypes of Phytophthora infestans, the oomycete pathogen causing late blight disease on potato and tomato. Carter's haplotypes I-a and I-b were included in Goodwin's haplotype A, while Carter's haplotypes II-a and II-b were included in Goodwin's haplotype B. In addition, haplotypes E and F were included in Carter's haplotype I-b. The mutational differences separating the various haplotypes were determined, and we propose that either haplotype I-b(A) or haplotype I-a(A) is the putative ancestral mtDNA of P. infestans, because either can center all the other haplotypes in a logical stepwise network of mutational changes. The occurrence of the six haplotypes in 548 isolates worldwide was determined. Haplotypes I-a and II-a were associated with diverse genotypes worldwide. As previously suggested, haplotype I-b was found only in the US-1 clonal lineage and its variants (n = 99 isolates from 16 countries on 5 continents), and haplotype II-b was limited to the US-6 clonal lineage and its derivatives (n = 36). In a confirmation of a previous suggestion, the randomly mating population in the Toluca Valley of central Mexico (n = 78) was monomorphic for mtDNA haplotype I-a(A). We hypothesize that selection there may be driving the dominance of that single mtDNA haplotype.


Palatoglossal fusion with cleft palate and hypoplasia of cerebellar vermis.
A new-born male presented within 12 h of birth with respiratory distress. On examination and workup, he had palatoglossal fusion, cleft palate and hypoplasia of the cerebellar vermis. A 2.5 Fr endotracheal tube was inserted into the pharynx through nostril as a nasopharyngeal stent, following which his respiratory distress improved. Once child was optimised, then feeding was started by nasogastric tube and feeds were tolerated well. Elective tracheostomy and gastrostomy were done, followed by release of adhesions between the tongue and palate at a later stage. Review of literature suggests that palatoglossal fusion is uncommon and presents as an emergency. Mostly, these oral synechiae are associated with digital and/or cardiac anomaly. Other disorders associated with intra-oral synechiae include congenital alveolar synechiae, van der Woude syndrome, popliteal pterygium syndrome and oromandibular limb hypogenesis syndrome. The authors report a hitherto undescribed association of palatoglossal fusion with cleft palate and hypoplasia of the cerebellar vermis.


Equilibrium of anchored interfaces with quenched disordered growth.
The roughening behavior of a one-dimensional interface fluctuating under quenched disorder growth is examined while keeping an anchored boundary. The latter introduces detailed balance conditions which allows for a simple but thorough analysis of equilibrium aspects at both macroscopic and microscopic scales. It is found that the interface roughens linearly with the substrate size only in the vicinity of special disorder realizations. Otherwise, it remains stiff and tilted.


New tapered metallic stent for unresectable malignant hilar bile duct obstruction.
To examine the usefulness of a new tapered metallic stent (MS) in patients with unresectable malignant hilar bile duct obstruction. This new tapered MS was placed in 11 patients with Bismuth II or severer unresectable malignant hilar bile duct obstruction, as a prospective study. The subjects were six patients with bile duct carcinoma, three with gallbladder cancer, and two with metastatic bile duct obstruction. Stenosis morphology was Bismuth II: 7, IIIa: 3, and IV: 1. UMIN Clinical Trial Registry (UMIN000004758). MS placement was 100% (11/11) successful. There were no procedural accidents. The mean patency period was 208.401 d, the median survival period was 142.000 d, and the mean survival period was 193.273 d. Occlusion rate was 36.4% (4/11); the causes of occlusion were ingrowth and overgrowth in 2 patients each, 18.2%, respectively. Patients with occlusion underwent endoscopic treatment one more time and all were treatable. The tapered MS proved useful in patients with unresectable malignant hilar bile duct obstruction because it provided a long patency period, enabled re-treatment by re-intervention, and no procedural accidents occurred.


Recent advances in preoperative and intraoperative nuclear medicine procedures in patients with primary hyperparathyroidism.
Although bilateral neck exploration is traditionally considered as the treatment of choice in patients with primary hyperparathyroidism (HPT), several surgical techniques of limited neck exploration have been proposed over the last 10 years in primary HPT patients with a high probability to be affected by a solitary parathyroid adenoma. The availability in recent years of highly sensitive and accurate preoperative imaging modalities, particularly the parathyroid scintigraphy with 99mTc-MIBI and high resolution neck ultrasonography, allowed to increase the rate of primary HPT patients as candidates to a selective parathyroidectomy. One of the most innovative techniques for limited surgery is the minimally invasive radio-guided parathyroidectomy that is based on the intraoperative detection of the parathyroid adenoma under the guidance of a gamma probe allowing the removal of the parathyroid adenoma through a small 2-cm skin incision. However, if a minimally invasive parathyroidectomy is taken into consideration, accurate preoperative imaging is mandatory not only to distinguish patients with a solitary parathyroid adenoma from those with multi-glandular disease but also to diagnose patients with concomitant thyroid nodule(s) that can cause false-positive results at radio-guided surgery. In the present study the most recent advances reached with preoperative localizing imaging of parathyroid adenomas are reviewed and the techniques proposed to perform a minimally invasive radio-guided surgery are discussed with particular regard to the therapeutic efficacy and cost-effectiveness analysis.


A New Look at Codon Usage and Protein Expression.
%MinMax, a model of intra-gene translational elongation rate, relies on codon usage frequencies. Historically, %MinMax has used tables that measure codon usage bias for all genes in an organism, such as those found at HIVE-CUT. In this paper, we provide evidence that codon usage bias based on all genes is insufficient to accurately measure absolute translation rate. We show that alternative "High-ϕ" codon usage tables, generated by another model (ROC-SEMPPR), are a promising alternative. By creating a hybrid model, future codon usage analyses and their applications (e.g., codon harmonization) are likely to more accurately measure the "tempo" of translation elongation. We also suggest a High-ϕ alternative to the Codon Adaptation Index (CAI), a classic metric of codon usage bias based on highly expressed genes. Significantly, our new alternative is equally well correlated with empirical data as traditional CAI without using experimentally determined expression counts as input.


Multimodal high-resolution retinal imaging using a camera-based DMD-integrated adaptive optics flood-illumination ophthalmoscope.
We demonstrate the feasibility of a multimodal adaptive optics flood-illumination ophthalmoscope, able to provide both bright-field and dark-field images (such as phase contrast). The multimodality was made possible by integrating a digital micromirror device (DMD) at the illumination path to project a sequence of complementary high-resolution patterns into the retina. Through a versatile post-processing method that digitally selects backscattered or multiply scattered photons, we were able: (1) to achieve up to four-fold contrast increase of bright-field images when imaging the photoreceptor mosaic and nerve fibers; and (2) to visualize translucent retinal features such as capillaries, red blood cells, vessel walls, ganglion cells, and photoreceptor inner segments through phase contrast.


Synthesis and Optical Properties of Near-Infrared meso-Phenyl-Substituted Symmetric Heptamethine Cyanine Dyes.
Heptamethine cyanine dyes are a class of near infrared fluorescence (NIRF) probes of great interest in bioanalytical and imaging applications due to their modifiability, allowing them to be tailored for particular applications. Generally, modifications at the meso-position of these dyes are achieved through Suzuki-Miyaura C-C coupling and SRN1 nucleophilic substitution of the chlorine atom at the meso-position of the dye. Herein, a series of 15 meso phenyl-substituted heptamethine cyanines was synthesized utilizing a modified dianil linker. Their optical properties, including molar absorptivity, fluorescence, Stokes shift, and quantum yield were measured. The HSA binding affinities of two representative compounds were measured and compared to that of a series of trimethine cyanines previously synthesized by our lab. The results indicate that the binding of these compounds to HSA is not only dependent on hydrophobicity, but may also be dependent on steric interferences in the binding site and structural dynamics of the NIRF compounds.


Assessment of recovery in older patients hospitalized with different diagnoses and functional levels, evaluated with and without geriatric assessment.
The objective of the present study was to investigate 1) the role of different admission diagnoses and 2) the degree of functional loss, on the rate of recovery of older patients after acute hospitalization. Furthermore, to compare the predictive value of simple assessments that can be carried out in a hospital lacking geriatric service, with assessments including geriatric screening tests. Prospective, observational cohort study, including 961community dwelling patients aged ≥ 70 years, transferred from medical, cardiac, pulmonary and orthopedic acute hospital departments to intermediate care in nursing home. Functional assessment with Barthel index (BI) was performed at admission to the nursing home and further geriatric assessment tests was performed during the first week. Logistic regression models with and without geriatric assessment were compared concerning the patients having 1) slow recovery (nursing home stay up to 2 months before return home) or, 2) poor recovery (dead or still in nursing home at 2 months). Slow recovery was independently associated with a diagnosis of non-vertebral fracture, BI subgroups 50-79 and <50, and, in the model including geriatric assessment, also with cognitive impairment. Poor recovery was more complex, and independently associated both with BI < 50, receiving home care before admission, higher age, admission with a non-vertebral fracture, and in the geriatric assessment model, cognitive impairment. Geriatric assessment is optimal for determining the recovery potential of older patients after acute hospitalization. As some hospitals lack geriatric services and ability to perform geriatric screening tests, a simpler assessment based on admission diagnoses and ADL function (BI), gives good information regarding the possible rehabilitation time and possibility to return home.


Tripodal exTTF-CTV hosts for fullerenes.
A receptor for fullerenes featuring three exTTF units linked to a CTV scaffold is described. The exTTF-CTV host forms remarkably stable complexes with both C(60) (log K(a) = 5.3 +/- 0.2) and C(70) (log K(a) = 6.3 +/- 0.6). Light-induced ESR spectra demonstrate that intracomplex PET processes take place in solution.


A stereoselective synthesis of BMS-262084, an azetidinone-based tryptase inhibitor.
A highly stereoselective synthesis of the novel tryptase inhibitor BMS-262084 was developed. Key to this synthesis was the discovery and development of a highly diastereoselective demethoxycarbonylation of diester 12 to form the trans-azetidinone 13. BMS-262084 was prepared in 10 steps from D-ornithine in 30% overall yield.


Do the species with facies reclinobunoides make up a clade?-A new Lomanius (Opiliones, Podoctidae) from Vietnam and a discussion on its relationships.
Lomanius annae sp. nov. is described from southern Vietnam. The species is characterized by the greatly developed dorso-basal process on cheliceral hand of males and by the partial effacement of all mesotergal grooves. The genus Lomanius contains four generic synonyms and currently comprises eight valid species distributed in China, Java, peninsular Malaysia, the Philippines, and Taiwan. The new species displays a general morphology similar to the former genus Paralomanius, with a combination of sexually dimorphic interocular mound (which is very large and strongly leaned back in males) and pedipalpus (which is extremely elongate in males). This morphological suite of features is herein called facies reclinobunoides. The replacement name Metibalonius triceratops nom. nov. is proposed for Trispinibunus abnormis Roewer, 1915, which is a junior secondary homonym of Ibalonius abnormis Strand, 1911. Finally, numerous morphological structures found in Podoctidae are recognized and named: (1) the cheliceral comb, present on cheliceral fingers, (2) the chained tubercular ridges, present on dorsal scutum and (3) several others related to the ocular region. The distribution of these two structures among podoctid species is not fully known, but both are absent in the former Ibaloniinae. We suggest that both structures may be useful to define supra-generic groups in the clade composed of the former Podoctinae and Erecananinae.


Nd:YAG 1064 nm laser treatment for onychomycosis - is it really effective? A prospective assessment for efficiency and factors contributing to response.
Onychomycosis is a highly prevalent and persistent nail disorder primarily caused by dermatophytes. The effectiveness of current topical and systemic antifungals is limited by the extent and severity of the infection, patient demographics and health status, hepatic toxicity, drug interactions and low compliance. Laser therapy is a promising modality for safe and cost-effective removal of mycotic nail. This prospective study assessed the performance of a multi-series long-pulsed Nd:YAG 1064 nm regimen (30-40 J/cm2 , 1 Hz) in the treatment of 213 mycotic nails in 31 patients. Pain and discomfort were scored at each treatment session and mycological and clinical cure rates were determined 3 months after the last treatment session. Patients presented with mostly severe (mean SCIO score: 21.9 ± 8.9), T. rubrum-positive (87.1%) infections. Most (61%) had a family history of onychomycosis and a significant proportion had comorbidities, including hypertension (38.7%), hyperlipidemia (35.5%) and/or diabetes (12.9%). Treatment was well tolerated and there were no reports of nail deformity or burns. By 3 months post-treatment, mycological cure was achieved by 4 (12.9%) and visual improvements were noted for 10 (32.3%) patients, including 3 (9.7%) with moderate to significant improvements. Clinical response correlated with baseline SCIO ≤ 20 (OR: 0.9 [0.13-6.52]), family history of onychomycosis (OR: 0.27 [0.04-1.50]) and comorbidities (OR: 0.44 [0.05-3.74]). In conclusion, Nd:YAG 1064 nm laser is safe and effective for the management of mild-to-moderate onychomycosis in diverse populations. Further studies will be necessary to adjust treatment parameters to patient and nail profiles and to determine the impact of combined laser and topical therapies.


Validity and reliability of the suggested immobilization test for measurement of restless legs syndrome severity in adults with multiple sclerosis.
Adults with multiple sclerosis (MS) often present with conditions that mimic restless legs syndrome (RLS), thereby adding complexity into the assessment of RLS severity. The current gold-standard measures of RLS severity rely on a fixed seven-day time frame, which limits the ability of these measures for studying acute changes in RLS severity. The present study examined if subjective and objective scores from the suggested immobilization test (SIT) provide a valid and reliable acute measure of RLS severity in persons with MS. Participants with MS and RLS (n = 20) and MS without RLS (n = 20) were matched by age, gender, and disability. All participants completed validated questionnaires for RLS severity followed by the SIT, conducted at 18:00 (±15 min) on the same day of the week for two consecutive weeks. Participants wore accelerometer devices for seven nights to capture periodic limb movements (PLMs) during the night. Self-reported RLS severity during the SIT had excellent construct validity and convergent validity, but moderate test-retest reliability. Device-measured PLMs, while not themselves a direct measure of RLS severity, were significantly associated with PLMs during the night and had excellent test-retest reliability during the SIT in adults with MS. Our results suggest that the SIT represents a valid acute measure for capturing self-reported sensory aspects of RLS severity and should be considered in future research and clinical practice as a standardized acute measure of subjective RLS severity in adults with MS who present with RLS.


Rule-based modulation of a sensorimotor transformation across cortical areas.
Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes rule information and uses this information to guide behavioral responses to sensory stimuli. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task in which they switched between two rules in different blocks of trials: licking in response to tactile stimuli applied to a whisker while rejecting visual stimuli, or licking to visual stimuli while rejecting the tactile stimuli. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, the single-trial activity of individual neurons distinguished between the two rules both prior to and in response to the tactile stimulus. Variable rule-dependent responses to identical stimuli could in principle occur via appropriate configuration of pre-stimulus preparatory states of a neural population, which would shape the subsequent response. We hypothesized that neural populations in S1, S2, MM and ALM would show preparatory activity states that were set in a rule-dependent manner to cause processing of sensory information according to the current rule. This hypothesis was supported for the motor cortical areas by findings that (1) the current task rule could be decoded from pre-stimulus population activity in ALM and MM; (2) neural subspaces containing the population activity differed between the two rules both prior to the stimulus and during the stimulus-evoked response; and (3) optogenetic disruption of pre-stimulus states within ALM and MM impaired task performance. Our findings indicate that flexible selection of an appropriate action in response to a sensory input can occur via configuration of preparatory states in the motor cortex. Task rules are reflected in preparatory activity in sensory and motor cortices.Neural subspaces for processing tactile signals depend on the current task rule.Motor cortical activity tracks rule switches and is required for flexible rule-guided behavior.


Evidence for the presence of carbamino compounds in human saliva.
The bicarbonate concentrations of whole saliva and of protein-free filtrates of saliva were measured to test for the presence of carbamino compounds. If no acid-evolved CO2 were derived from the salivary proteins, then the two measured bicarbonate concentrations should be identical. Instead, the bicarbonate concentrations of the whole saliva samples were on the average 30% higher than that of their filtrates. The results are consistent with the conclusion that carbamino compounds account for the differences. Similar findings were obtained with samples of resting whole saliva and parotid saliva.


Spatial regulation of monolignol biosynthesis and laccase genes control developmental and stress-related lignin in flax.
Bast fibres are characterized by very thick secondary cell walls containing high amounts of cellulose and low lignin contents in contrast to the heavily lignified cell walls typically found in the xylem tissues. To improve the quality of the fiber-based products in the future, a thorough understanding of the main cell wall polymer biosynthetic pathways is required. In this study we have carried out a characterization of the genes involved in lignin biosynthesis in flax along with some of their regulation mechanisms. We have first identified the members of the phenylpropanoid gene families through a combination of in silico approaches. The more specific lignin genes were further characterized by high throughput transcriptomic approaches in different organs and physiological conditions and their cell/tissue expression was localized in the stems, roots and leaves. Laccases play an important role in the polymerization of monolignols. This multigenic family was determined and a miRNA was identified to play a role in the posttranscriptional regulation by cleaving the transcripts of some specific genes shown to be expressed in lignified tissues. In situ hybridization also showed that the miRNA precursor was expressed in the young xylem cells located near the vascular cambium. The results obtained in this work also allowed us to determine that most of the genes involved in lignin biosynthesis are included in a unique co-expression cluster and that MYB transcription factors are potentially good candidates for regulating these genes. Target engineering of cell walls to improve plant product quality requires good knowledge of the genes responsible for the production of the main polymers. For bast fiber plants such as flax, it is important to target the correct genes from the beginning since the difficulty to produce transgenic material does not make possible to test a large number of genes. Our work determined which of these genes could be potentially modified and showed that it was possible to target different regulatory pathways to modify lignification.


Context-Dependent Modulation of Excitatory Synaptic Strength by Synaptically Released Zinc.
Synaptically released zinc inhibits baseline excitatory neurotransmission; however, the role of this neuromodulator on short-term plasticity during different levels of synaptic activity remains largely unknown. This lack of knowledge prevents our understanding of information transfer across zinc-releasing synapses, including 50% of excitatory synapses in cortical areas. We used in vitro electrophysiology in mouse brain slices and discovered that the effects of zinc on excitatory postsynaptic current (EPSC) amplitudes are context-dependent. At lower frequencies of activity, synaptically released zinc reduces EPSC amplitudes. In contrast, at higher stimulation frequencies and vesicular release probability (Pr), zinc inhibits EPSC amplitudes during the first few stimuli but leads to enhanced steady-state EPSC amplitudes during subsequent stimuli. This paradoxical enhancement is due to zinc-dependent potentiation of synaptic facilitation via the recruitment of endocannabinoid signaling. Together, these findings demonstrate that synaptically released zinc is a modulator of excitatory short-term plasticity, which shapes information transfer among excitatory synapses.


Transference, counter-transference and repetition: some implications for nursing practice.
This discussion paper offers an introductory text for nurses and explores the psychoanalytic ideas of transference, counter-transference and repetition compulsion. Disguised case vignettes provide illustrations of the ideas as they might apply to nursing, including professional practice and occupational choice. The literature suggests that transference can be a source of creativity as well as destructiveness and influence important communications with oneself and others including the choice of nursing and other health professions as an occupation. Recognizing possibilities of transference, counter-transference along with repetitive patterns of behaviours, can help nurses of all specialities to address situations constructively by responding thoughtfully and appropriately. This discussion concludes with the suggestions that we know little about the motivational factors underlying nursing as an occupational preference; moreover, nursing does not have a culture of personal therapy. As such nurses are denied opportunities to understand the possible reasons underlying their occupational choice or gain experiential knowledge of interpersonal dynamics occurring between patients and colleagues. Transference and counter-transference are thought to have some bearing on all relationships. Forming a natural part of the way human beings relate to each other, transference and counter-transference can bring about sincere human interest, caring and concern. However, there is also potential for disagreements. Recognizing the possible origins of relational difficulties can offer opportunities for professional development to nurses along with the benefits for health service users.


[Surgical results of osteosynthesis in fracture of the mandible].
In the study the results of osteosynthesis in fracture of the mandible with miniplates and osteosuture. The 80 patients in two groups with 40 subjects in each were suffering from fracture of the mandible. In 25 of them the miniplate osteosynthesis was performed. The healing of wound, functional evaluation and the state of postoperative scar were described. Complication in both examined groups were similar. No difference was noticed in size and picture of scars after miniplate osteosynthesis and osteosuture. In 62.5% of miniplate osteosynthesis the intraoral way was used to diminish the postoperative scar. The good results of this method indicate an usefulness in clinical practice.


Card and board game design for medical education: length and complexity considerations.
There is growing use of games for health professions education. Card and board games are relatively easy to develop, effective for education, supported by educational theory, and generally well accepted by learners; yet, they remain relatively infrequently described in the medical education literature. A questionnaire was developed to understand barriers to use of card and board games and to understand user preferences to inform their development. The questionnaire was offered to students and educators downloading a printable antibiotic card game online. The questionnaire was completed by 335 health professionals primarily by physicians, pharmacists, and their trainees. Participants described preferences for shorter games and games with lower complexity. Player counts in the two to four range were the most commonly desired. The most frequently cited barriers were lack of availability in desired subjects, cost, and concerns about content accuracy. Educators looking to develop or use serious card and board games should start with shorter, lower-complexity games. Methods to assure and demonstrate content accuracy for educational games should be explored by educators and researchers.


Anatomy and Function of the Primate Entorhinal Cortex.
The entorhinal cortex (EC) is a critical element of the hippocampal formation located within the medial temporal lobe (MTL) in primates. The EC has historically received attention for being the primary mediator of cortical information going into and coming from the hippocampus proper. In this review, we highlight the significance of the EC as a major player in memory processing, along with other associated structures in the primate MTL. The complex, convergent topographies of cortical and subcortical input to the EC, combined with short-range intrinsic connectivity and the selective targeting of EC efferents to the hippocampus, provide evidence for subregional specialization and integration of information beyond what would be expected if this structure were a simple conduit of information for the hippocampus. Lesion studies of the EC provide evidence implicating this region as critical for memory and the flexible use of complex relational associations between experienced events. The physiology of this structure's constituent principal cells mirrors the complexity of its anatomy. EC neurons respond preferentially to aspects of memory-dependent paradigms including object, place, and time. EC neurons also show striking spatial representations as primates explore visual space, similar to those identified in rodents navigating physical space. In this review, we highlight the great strides that have been made toward furthering our understanding of the primate EC, and we identify paths forward for future experiments to provide additional insight into the role of this structure in learning and memory.


Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody.
Tick-borne encephalitis virus (TBEV) causes 13,000 cases of human meningitis and encephalitis annually. However, the structure of the TBEV virion and its interactions with antibodies are unknown. Here, we present cryo-EM structures of the native TBEV virion and its complex with Fab fragments of neutralizing antibody 19/1786. Flavivirus genome delivery depends on membrane fusion that is triggered at low pH. The virion structure indicates that the repulsive interactions of histidine side chains, which become protonated at low pH, may contribute to the disruption of heterotetramers of the TBEV envelope and membrane proteins and induce detachment of the envelope protein ectodomains from the virus membrane. The Fab fragments bind to 120 out of the 180 envelope glycoproteins of the TBEV virion. Unlike most of the previously studied flavivirus-neutralizing antibodies, the Fab fragments do not lock the E-proteins in the native-like arrangement, but interfere with the process of virus-induced membrane fusion.


Concomitant use of an infrared fractional laser with low-dose isotretinoin for the treatment of acne and acne scars.
Acne scarring has lifelong sequelae. Fractional photothermolysis (FP) has been shown to provide fast recovery from acne within a short period, thereby aiding skin rejuvenation. Isotretinoin is a well-known, effective drug for the treatment of severe recalcitrant acne. This study investigated the safety and the efficacy of infrared fractional laser treatment in conjunction with low-dose isotretinoin for the treatment of acne and acne scars. A 1550 nm Erbium-doped fiber laser was used to treat 35 patients with acne scarring. All the patients had taken isotretinoin (10 mg/day) for more than one month prior to the commencement of the fractional laser treatment. There was no aggravation of acne scars, hypertrophic scars, or keloids. Most of the patients (33 patients) received reduced microthermal damage zone (MTZ) treatment. Eighty percent of the treated patients (28 patients) demonstrated more than a fair improvement. The total average score on the global acne scarring classification before treatment was 13.5, and the score after treatment was 11.2. Acne and acne scars can be treated more effectively by concomitant use of an infrared fractional laser with low-dose isotretinoin with reduced MTZ densities. Most patients showed more than a fair improvement, and there was no aggravation of the scars.


Iron absorption is more closely related to iron status than to daily iron intake in 12- to 48-mo-old children.
Few studies have evaluated iron absorption in small children after the first year of life. Our objectives were to examine the relations among iron intake, iron absorption, and iron status in a group of healthy children. We studied 28 children, ages 12 to 48 mo, after a 7-d home adaptation to a diet representative of their usual daily mineral intake. A multi-tracer stable isotope study was performed to assess iron absorption both from a meal ((58)Fe) and from a reference iron dose ((57)Fe) given with ascorbic acid without a meal. Iron intake was 6.9 +/- 2.4 mg, approximately the 35th percentile of typical U.S. intakes. Absorption of (58)Fe was related to serum ferritin (r(2) = 0.319, P = 0.0018) and more so to reference dose iron absorption (r(2) = 0.653, P < 0.0001). Iron absorption was negatively correlated with zinc intake (r(2) = 0.090, P = 0.0049) but was not correlated with iron intake (P = 0.20). However, zinc intake was not correlated with measures of iron status, including reference dose iron absorption and serum ferritin (r(2) < 0.1, P > 0.25). Total absorbed iron was similar to needs estimated by the Institute of Medicine. We conclude that iron absorption in young children is more closely related to iron status than to iron intake. Reference dose iron absorption may be superior to serum ferritin as a surrogate measure for iron status in this age group. Although zinc intake may affect iron absorption from a meal, it does not appear to have a detectable effect on overall iron status in otherwise well-nourished children.


Factors affecting prolonged length of stay in psychiatric patients in Japan: A retrospective observational study.
Hospital length of stay (LOS) is one of the stratified measures of health-care efficiency and is commonly used to assess performance of psychiatric care. The aim of this study was to identify risk factors for prolonged LOS of psychiatric patients. We retrospectively analyzed adult psychiatric patients (ICD-10; F00-F99) between April 2012 and March 2014 in the Japanese Diagnosis Procedure Combination database. We examined factors affecting prolonged LOS using multivariable logistic regression analysis. Subgroup analyses of the logistic regression were undertaken according to two diagnostic groups (F20-F29 and F30-F39). A total of 34 326 patients admitted to and discharged from psychiatric beds were included. Older age, lower Global Assessment of Functioning score, involuntary commitment, several psychiatric services, certain other patient factors, academic hospitals, public hospitals, and higher density of psychiatric beds were significantly associated with prolonged LOS. Hospital patient volume was significantly associated with shorter LOS. In the subgroup analyses, most of these factors were consistent although some were not associated with prolonged LOS. Not only clinical factors but also institutional characteristics were associated with prolonged LOS. Our study provided useful information for improvement in psychiatric services and indicated the need to consider the division of roles between healthcare/welfare institutions and psychiatric-related resource allocation. Interventions should be considered for achieving shorter LOS for psychiatric patients.


The use of infrared thermography and accelerometers for remote monitoring of dairy cow health and welfare.
Increasing reliance on automated systems on-farm has led to a need for remote monitoring of health and welfare. We aimed to validate 2 methods that could be integrated into automated systems currently in use: infrared thermography (IRT) to measure respiration rate (RR), and accelerometers to measure the flinch, step, kick (FSK) response and assessing stress and discomfort. We monitored 22 multiparous, nonlactating, Friesian and Friesian × Jersey cows (average 5.1 yr of age) during a baseline period (2 min), a restraint in a crush (2 min), and then a recovery period after exposure to a startle (2 min). We measured RR with continuous IRT imaging of airflow through the nostrils and by counting flank movements from video and live recordings. We recorded heart rate (HR) and HR variability using HR monitors, and we recorded FSK from continuous video analysis of leg movements and indirectly using accelerometers attached to both hind legs. The FSK response was scored between 1 and 4 based on the height and direction of each leg movement. We observed no change in RR, HR variability, or FSK in response to the startle; however, HR increased briefly by 10 bpm. Bland-Altman plots indicated good agreement between the different methods of measuring RR, with average differences of -0.01 ± 0.87, 0.83 ± 0.57, and 0.37 ± 1.02 breaths/min for video versus live, IRT versus live and IRT versus video, respectively. Acceleration was also highly correlated with FSK scores of ≤3 (R2 = 0.96) and ≤2 (R2 = 0.89) and moderately correlated with FSK scores of 1 (R2 = 0.66) over the 4-min sampling period. The results show that accelerometers can provide an indirect measure of the FSK response, and IRT can be used reliably to measure RR. With further development, both technologies could be integrated into existing systems for remote monitoring of dairy cows' health and welfare on-farm.


Continuous optical generation of microwave signals for fountain clocks.
For the optical generation of ultrastable microwave signals for fountain clocks, we developed a setup based on a cavity stabilized laser and a commercial frequency comb. The robust system, in operation since 2020, is locked to a 100 MHz output frequency of a hydrogen maser and provides an ultrastable 9.6 GHz signal for the interrogation of atoms in two cesium fountain clocks, acting as primary frequency standards. Measurements reveal that the system provides a phase noise level that enables quantum projection noise limited fountain frequency instabilities at the low 10-14(τ/s)-1/2 level. At the same time, it offers largely maintenance-free operation.


A study of the innervation of the taenia coli.
An electrophysiological and anatomical study of the guinea pig taenia coli is reported. Changing the membrane potential of single cells cannot modulate the rate of firing action potentials but does reveal electrical coupling between the cells during propagation. The amplitude of the junction potentials which occur during transmission from inhibitory nerves is unaffected in many cells during alteration of the membrane potential, indicating electrical coupling during transmission. The taenia coli is shown to consist of smooth muscle bundles which anastomose. There are tight junctions between the cells in the bundles, and these probably provide the pathway for the electrical coupling. The smooth muscle cells towards the serosal surface of the taenia coli are shown electrophysiologically to have an extensive intramural inhibitory innervation, but a sparse sympathetic inhibitory and cholinergic excitatory innervation. These results are in accordance with the distribution of these nerves as determined histochemically. As single axons are only rarely observed in the taenia coli, it is suggested that the only muscle cells which undergo permeability changes during transmission are those adjacent to varicosities in the nerve bundles. The remaining muscle cells then undergo potential changes during transmission because of electrical coupling through the tight junctions.


Expansion and Adipogenesis Induction of Adipocyte Progenitors from Perivascular Adipose Tissue Isolated by Magnetic Activated Cell Sorting.
Expansion of Perivascular Adipose Tissue (PVAT), a major regulator of vascular function through paracrine signaling, is directly related to the development of hypertension during obesity. The extent of hypertrophy and hyperplasia depends on depot location, sex, and the type of Adipocyte Progenitor Cell (APC) phenotypes present. Techniques used for APC and preadipocytes isolation in the last 10 years have drastically improved the accuracy at which individual cells can be identified based on specific cell surface markers. However, isolation of APC and adipocytes can be a challenge due to the fragility of the cell, especially if the intact cell must be retained for cell culture applications. Magnetic-activated Cell Sorting (MCS) provides a method of isolating greater number of viable APC per weight unit of adipose tissue. APC harvested by MCS can be used for in vitro protocols to expand preadipocytes and differentiate them into adipocytes through use of growth factor cocktails allowing for analysis of the prolific and adipogenic potential retained by the cells. This experiment focused on the aortic and mesenteric PVAT depots, which play key roles in the development of cardiovascular disease during expansion. These protocols describe methods to isolate, expand, and differentiate a defined population of APC. This MCS protocol allows isolation to be used in any experiment where cell sorting is needed with minimal equipment or training. These techniques can aid further experiments to determine the functionality of specific cell populations based on the presence of cell surface markers.


An amber suppressor of Escherichia coli strain KO1.
The suppression characteristics of Escherichia coli strain KO1 have been investigated. The growth patterns of nonsense mutants of RNA (GA and f2) and DNA (lambda and T4) phages suggested that KO1 carried an amber, but not ochre or opal suppressors. The comparison of KO1 with previously identified amber suppressors indicated that KO1 differed from su1, su3 and su6 in its suppression pattern. KO1 and su2 shared some properties in common, for instance, their ability to suppress GA amber mutants with one exception (amN20) and the restriction of suppression capacity by the strr mutation. However, the suppression efficiency of KO1 (48%) was about three times that of su2 (18%). A possibility that KO1 contained a new amber suppressor is discussed.


Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases.
Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.


The fate of redundant cues in human predictive learning: The outcome ratio effect.
In four experiments, participants were shown a sequence of pairs of pictures of food and asked to predict whether each pair signalled an allergic reaction in a hypothetical patient. The pairs of pictures were used to present two simple discriminations that differed in their outcome ratio. A rich discrimination, 3AX+ BX-, involved three trials in which the compound of two foods, AX, was followed by a reaction, for every trial in which the compound BX was not followed by the outcome. A lean discrimination, CY+ 3DY- was based on the opposite outcome ratio. Upon the completion of this training, participants were asked to rate how likely an individual food would be followed by the allergic reaction. In each experiment, the rating for X was stronger than for Y. This outcome ratio effect poses a challenge for theories of learning that assume changes in associative strength are governed by a common error term, based on the significance of all the cues present on a trial. Instead, the results are consistent with the assumption that changes in associative strength are governed by an individual error term, based on the significance of a single cue.


Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells.
Metastasis underlies most colorectal cancer mortality. Cancer cells spread through the body as single cells or small clusters of cells that have an invasive, mesenchymal, nonproliferative phenotype. At the secondary site, they revert to a proliferative "tumor constructing" epithelial phenotype to rebuild a tumor. We previously developed a unique in vitro three-dimensional model, called LIM1863-Mph, which faithfully recapitulates these reversible transitions that underpin colorectal cancer metastasis. Wnt signaling plays a key role in these transitions and is initiated by the coupling of extracellular Wnt to Frizzled (FZD). Using the LIM1863-Mph model system we demonstrated that the Wnt receptor FZD7 is necessary for mesenchymal to epithelial transition (MET). Here we investigate the role of Wnt in MET. Wnt secretion is dependent on palmitoylation by Porcupine (PORC). A PORC inhibitor (IWP2) that prevents Wnt secretion, blocked the epithelial transition of mesenchymal LIM1863-Mph cells. Wnt gene array analysis identified several Wnts that are upregulated in epithelial compared with mesenchymal LIM1863-Mph cells, suggesting these ligands in MET. Wnt2B was the most abundant differentially expressed Wnt gene. Indeed, recombinant Wnt2B could overcome the IWP2-mediated block in epithelial transition of mesenchymal LIM1863-Mph cells. Wnt2B co-operates with Frizzled7 to mediate MET in colorectal cancer. Developmental Dynamics 247:521-530, 2018. © 2017 Wiley Periodicals, Inc.


AF2Complex predicts direct physical interactions in multimeric proteins with deep learning.
Accurate descriptions of protein-protein interactions are essential for understanding biological systems. Remarkably accurate atomic structures have been recently computed for individual proteins by AlphaFold2 (AF2). Here, we demonstrate that the same neural network models from AF2 developed for single protein sequences can be adapted to predict the structures of multimeric protein complexes without retraining. In contrast to common approaches, our method, AF2Complex, does not require paired multiple sequence alignments. It achieves higher accuracy than some complex protein-protein docking strategies and provides a significant improvement over AF-Multimer, a development of AlphaFold for multimeric proteins. Moreover, we introduce metrics for predicting direct protein-protein interactions between arbitrary protein pairs and validate AF2Complex on some challenging benchmark sets and the E. coli proteome. Lastly, using the cytochrome c biogenesis system I as an example, we present high-confidence models of three sought-after assemblies formed by eight members of this system.


Aggregation and gelation of oat β-glucan in aqueous solution probed by NMR relaxometry.
Nuclear magnetic resonance was used to study water proton transverse relaxation in oat β-glucan aqueous solutions during storage. The molecular weights of the samples ranged from 112 to 494kDa. The polysaccharide structure was identified by IR, GC-MS, NMR spectroscopy, and high performance anion exchange chromatography. In 1% solutions, 494kDa β-glucan formed stable solution phase. Aggregates were generated in the solution of low molecular weight polysaccharide. The transverse relaxation time of water associated with the aggregate microphase was about 15ms. The majority of the solution was bulk water, with a relaxation time of 800-1600ms. The proton exchange rate was about 103s-1, calculated from two-site exchange model. The proportion of β-glucan in the aggregate microphase increased from 0 to over 80% of the total β-glucan during storage of 112kDa samples. In the 4% solutions, the evolution of water proton relaxation associated with the gel network can be explained by the fractal structure theory. The relaxation behavior suggested the growth and syneresis of the gel network during the gelation of the low molecular weight β-glucan solutions.


Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine.
To investigate the effects of long term thyroid hormone suppressive therapy on the heart, 20 patients were evaluated by noninvasive techniques. Of them, 10 were athyreotic after surgery for differentiated thyroid cancer, and 10 had diffuse or nodular goiter. The mean age of the group was 39 +/- 11 yr. Twenty age- and sex-matched subjects served as controls. The mean dose of levothyroxine was 163 +/- 34 micrograms daily. Plasma TSH was undetectable in all patients. Mean serum T4, free T4, and sex hormone-binding globulin were significantly higher (P < 0.001), whereas mean serum T3, free T3, and osteocalcin did not differ from control levels. Cardiac evaluation consisted of a standard 12-lead electrocardiogram, an ambulatory electrocardiographic monitoring (Holter), and an echocardiographic study. Two patients showed abnormal electrocardiograms for left ventricular hypertrophy. Holter demonstrated an increase in average heart rate (84 +/- 7 vs. 70 +/- 6 beats/min; P < 0.01). Prevalence of atrial premature beats was higher in the patient group than in the control group (100% vs. 60%; P < 0.006). The echocardiogram showed an increased left ventricular mass index in the patient group (97 +/- 24 vs. 80 +/- 18 g/m2; P < 0.02). Furthermore, left ventricular systolic function was enhanced, with higher values of fractional shortening (38 +/- 7% vs. 34 +/- 4%; P < 0.05) and rate-adjusted velocity of shortening (1.2 +/- 0.13 vs. 1.05 +/- 0.14 circumferences/sec; P < 0.01). These findings indicate that long term levothyroxine therapy at suppressive doses markedly affects cardiac function.


Neuroinflammation in a Mouse Model of Alzheimer's Disease versus Auditory Dysfunction: Machine Learning Interpretation and Analysis.
Auditory dysfunction, including central auditory hyperactivity, hearing loss and hearing in noise deficits, has been reported in 5xFAD Alzheimer's disease (AD) mice, suggesting a causal relationship between amyloidosis and auditory dysfunction. Central auditory hyperactivity correlated in time with small amounts of plaque deposition in the inferior colliculus and medial geniculate body, which are the auditory midbrain and thalamus, respectively. Neuroinflammation has been associated with excitation to inhibition imbalance in the central nervous system, and therefore has been proposed as a link between central auditory hyperactivity and AD in our previous report. However, neuroinflammation in the auditory pathway has not been investigated in mouse amyloidosis models. Machine learning was used to classify the previously obtained auditory brainstem responses (ABRs) from 5xFAD mice and their wild type (WT) littermates. Neuroinflammation was assessed in six auditory-related regions of the cortex, thalamus, and brainstem. Cochlear pathology was assessed in cryosection and whole mount. Behavioral changes were assessed with fear conditioning, open field testing and novel objection recognition. Reliable machine learning classification of 5xFAD and WT littermate ABRs were achieved for 6M and 12M, but not 3M. The top features for accurate classification at 6 months of age were characteristics of Waves IV and V. Microglial and astrocytic activation were pronounced in 5xFAD inferior colliculus and medial geniculate body at 6 months, two neural centers that are thought to contribute to these waves. Lower regions of the brainstem were unaffected, and cortical auditory centers also displayed inflammation beginning at 6 months. No losses were seen in numbers of spiral ganglion neurons (SGNs), auditory synapses, or efferent synapses in the cochlea. 5xFAD mice had reduced responses to tones in fear conditioning compared to WT littermates beginning at 6 months. Serial use of ABR in early AD patients represents a promising approach for early and inexpensive detection of neuroinflammation in higher auditory brainstem processing centers. As changes in auditory processing are strongly linked to AD progression, central auditory hyperactivity may serve as a biomarker for AD progression and/or stratify AD patients into distinct populations.


Partly Separated Activations in the Spatial Distribution between de-qi and Sharp Pain during Acupuncture Stimulation: An fMRI-Based Study.
Nowadays, functional magnetic resonance imaging (fMRI) has become one of the most important ways to explore the central mechanism of acupuncture. Among these studies, activations around the somatosensory-related brain network had the most robust blood oxygen level-dependent (BOLD) responses. However, due to the insufficient control of the subjective sensations during acupuncture stimulation, whether these robust activations reflected the pattern of de-qi, sharp pain, or mixed (de-qi + sharp pain) sensations was largely unknown. The current study recruited 50 subjects and grouped them into two groups according to whether he/she experienced sharp pain during acupuncture stimulation to give a definite answer to the aforesaid question. Our results indicated that BOLD responses associated with de-qi during acupuncture stimulation at ST36 were activation dominated. Furthermore, both the quantitative and qualitative differences of BOLD responses between de-qi and mixed sensations evoked by acupuncture stimulation were significant. The pattern of BOLD responses of sharp pain might be partly separated from that of de-qi in the spatial distribution. Therefore, we proposed that in order to explore the specific central mechanism of acupuncture, subjects with sharp pain should be excluded from those with only de-qi.


Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables?
Indole-3-carbinol (I3C) is one of several compounds in brassica vegetables that demonstrate anticarcinogenic effects in experimental animals. A review of Medline and CancerLit databases indicated that interest in I3C, as a cancer chemopreventive agent, has increased significantly in the past 5-10 years. Whereas most studies report inhibitory or protective effects of I3C in vivo, a few provide clear evidence for promotion or enhancement of carcinogenesis, depending upon the initiator, exposure protocol and species. In the absence of detailed information on the inhibitory and in particular, promotional mechanisms, it would seem advisable to proceed with caution before including I3C in extensive human clinical trials.


Dissection of a natural RNA silencing process in the Drosophila melanogaster germ line.
To date, few natural cases of RNA-silencing-mediated regulation have been described. Here, we analyzed repression of testis-expressed Stellate genes by the homologous Suppressors of Stellate [Su(Ste)] repeats that produce sense and antisense short RNAs. The Stellate promoter is dispensable for suppression, but local disturbance of complementarity between the Stellate transcript and the Su(Ste) repeats impairs silencing. Using in situ RNA hybridization, we found temporal control of the expression and spatial distribution of sense and antisense Stellate and Su(Ste) transcripts in germinal cells. Antisense Su(Ste) transcripts accumulate in the nuclei of early spermatocytes before the appearance of sense transcripts. The sense and antisense transcripts are colocalized in the nuclei of mature spermatocytes, placing the initial step of silencing in the nucleus and suggesting formation of double-stranded RNA. Mutations in the aubergine and spindle-E genes, members of the Argonaute and RNA helicase gene families, respectively, impair silencing by eliminating the short Su(Ste) RNA, but have no effect on microRNA production. Thus, different small RNA-containing complexes operate in the male germ line.


An Experience of an Individual With a Chronic Wound in an Open Abdomen: A Grounded Theory.
The open abdomen (OA) surgical technique has become an option for treating complex abdominal injuries; however, complications leading to late closure conditions might arise. In these cases the wound must be left open, which greatly impacts the patient's life. The author aims to describe the experiences of individuals with a chronic OA wound. Qualitative design using grounded theory was utilized. This study was carried out with a group of 28 adults who were treated with OA technique and whose wound had remained open for more than a month in duration and only received outpatient wound care. Data were collected through open interviews and examined under continuous comparison. The average age of the respondents was 45 years, and their wound, treated with OA due to severe abdominal infection, remained open between 2 months and 8 years. An emergent theory was developed to describe how people facing this experience undergo a process of 4 stages: 1) finding an OA wound upon waking, 2) feeling desperate about the healing process and the limitations involved, 3) regaining control of their life, and 4) taking advantage of their second chance at life with an OA wound. This study provides insight for nurses and other health care professionals into the experiences of patients with a chronic OA wound and proposes an emerging theory based on the conceptualization of these experiences.


Coronary arteriography and coronary bypass survey among whites and other racial groups relative to hospital-based incidence rates for coronary artery disease: findings from NHDS.
To assess racial differences in health care utilization for coronary artery disease (CAD) the data of the National Hospital Discharge Survey (NHDS) from 1979-84 were examined. Discharge rates for acute myocardial infarction (AMI) were utilized as a measure of hospital-based incidence and relative need for the designated cardiac procedures. Although 35-74 year old Black men had discharge rates of AMI that were 77 per cent of those observed for White men, they underwent coronary arteriography half as often and were only a third as likely to have coronary artery bypass graft (CABG) surgery. Black women in this age range were hospitalized at a slightly higher rate than White women for AMI, yet experienced a 19 per cent lower rate of coronary arteriography and a 52 per cent lower rate of CABG surgery. These data suggest a racial bias in the pattern of care delivered for CAD in US hospitals at the present time.


Constriction of the ductus arteriosus, severe right ventricular hypertension, and a right ventricular aneurysm in a fetus after maternal use of a topical treatment for striae gravidarum.
Fetal constriction of the ductus arteriosus is a complication of maternal non-steroidal anti-inflammatory drug use and polyphenol-rich food intake. It is unclear as to whether polyphenol-containing topical treatments have similar effects. We present a case of fetal constriction of the ductus arteriosus, severe right ventricular hypertension, and a right ventricular aneurysm associated with maternal use of a topical treatment for striae gravidarum.


Anti-androgenic and hair growth promoting activities of Lygodii spora (spore of Lygodium japonicum) I. Active constituents inhibiting testosterone 5alpha-reductase.
The aqueous ethanol extract of Lygodii Spora (spore of Lygodium japonicum (Thunb.) Sw.) showed in vitro testosterone 5alpha-reductase inhibitory activity and in vivo anti-androgenic activity using growth of flank organ in castrated Syrian hamsters and hair regrowth after shaving in testosterone-treated C57Black/6CrSlc mice. From the lipophilic constituents of Lygodii Spora, oleic, linoleic and palmitic acids were identified as the main active principles inhibiting testosterone 5alpha-reductase.


Human monocytes and lymphocytes differ in the rate of DNA repair synthesis and viability after exposure to nitrogen mustard.
Unscheduled DNA synthesis was studied in human lymphocytes and monocytes after treatment with nitrogen mustard, methyl-methane-sulphonate and ultraviolet irradiation. The unscheduled DNA synthesis was about 4 times higher in monocytes than in lymphocytes after treatment with nitrogen mustard. Treatment with methyl-methane-sulphonate or ultraviolet irradiation confirmed the higher capacity for unscheduled DNA synthesis in the monocytes. When Ficoll-Isopaque-isolated mononuclear cells were exposed to various doses of nitrogen mustard and incubated for different periods, a dose- and time-dependent increase in trypan blue uptake was found. Furthermore, a corresponding dose- and time-dependent decrease was noted in 3H-uridine incorporation. Since trypan blue uptake will not enable differentiation between monocytes and lymphocytes appearing as a mixed cell population, 3H-uridine flash labeling index was studied after exposure to nitrogen mustard. There was a dose- and time-dependent decrease in 3H-uridine labeling index, suggesting a correlation between the absence of 3H-uridine incorporation and increase in trypan blue uptake. When compared to monocytes, the lymphocytes were more affected in this respect after exposure to nitrogen mustard. The possibility that differences in cytotoxic effect may be related to DNA repair mechanisms is discussed.


Effect of vanadium on L-ascorbic acid concentration in rat tissues.
1. Two-month old Wistar rats of both sexes received, as sole drinking liquid, an aqueous solution of ammonium metavanadate (AMV) at a concentration of 0.01, 0.05, 0.15 and 0.30 mg V/ml (corresponding to 0.2, 1, 3 and 6 mM solution) over 4 weeks. 2. In the animal groups receiving AMV solution of 0.15 or 0.30 mg V/ml concentrations to drink, a statistically significant decrease of the uptake of food and AMV solution was observed, as compared with food and water taken up in the same time by the control group. 3. Moreover, a distinct decrease of the L-ascorbic acid level was noted in the liver, kidneys, spleen and adrenals. These differences proved statistically significant in single cases of animals receiving a solution of 0.05 and 0.15 mg V/ml concentration and in all animals given the solution at the highest vanadium concentration.


Comparative evaluation of the group of teeth with the best prediction value in the mixed dentition analysis.
Mixed dentition analysis allows the prediction of the tooth width of non erupted permanent canines and premolars (SPCP). It is an essential factor in treatment planning since it could predict a tooth-size to arch-length discrepancy. The aim of this study was to determine which group of permanent teeth presented the best prediction capability for the width sums of the unerupted canine and premolars in an Italian sample. A total of 150 subjects with complete permanent dentition were selected. Their dental casts were measured to 0.01 mm with a digital caliper. Pearson correlation and T-test were used for the statistical analysis. The combination of the sums of the four lower incisors and the first upper molars showed the best prediction capability for the SPCP in the Italian sample. Moreover new regression equations were formulated including sex and arch as additional predictor variables. In 80% of the cases estimated differences between the predicted and the actual values were smaller than 1 mm. It can be concluded that the new regression equations proposed seemed to show good accuracy.


Production of size controlled aluminum and alumina nanoparticles via pulsed laser ablation in water.
An Al metal plate was ablated by a pulsed Nd-YAG laser to produce nano-structured Al and gamma-Al2O3 in deionized water in the absence of any surfactants or catalysts. In this study, the mean diameter and the width of size distribution of the nanoparticles was influenced by the laser power, resulting in the production of smaller and larger sizes of nanoparticles with higher and lower laser power, respectively. The influence of laser power on the mean diameter and the width of size distribution of as-prepared nanoparticles generated by the laser ablation process was explained by the space homogeneity of the plasma plume, where the nucleation of nanoparticles has occurred. Further explanations of the influence of laser power on the size distribution are proposed. Furthermore, structural and morphological characterization of aluminum and gamma-Al2O3 nanoparticles was conducted by X-ray diffraction (XRD) and field emission scanning electron microscope (FE-SEM).


Factitial panniculitis and necrotizing fasciitis in juvenile diabetes.
A fifteen-year-old diabetic girl developed multiple inflammatory areas on the extremities and abdominal wall at the site of insulin injection. The bizarre clinical manifestations led to great difficulties in determining both its etiology and its treatment. However, three months after her initial hospitalization, we found that the lesions were probably secondary to self-injection with a chemical agent rather than a result of insulin allergy. If idiopathic recurrent dermal infection is observed, then factitial origin should be suspected.


Malignant peripheral nerve sheath tumor in the anterior mediastinum: A case report.
Malignant peripheral nerve sheath tumors (MPNSTs) are rare neoplasms, accounting for only 5% of all malignant soft-tissue sarcomas. This is the case report of a 28-year-old male patient with a MPNST located in the anterior mediastinum, originating from the phrenic nerve. The patient presented with an abnormal shadow on chest radiography and a 10-cm mass in the right anterior mediastinum was identified on computed tomography and magnetic resonance imaging. The patient subsequently underwent surgical resection. The tumor originated from the right phrenic nerve and was tightly adherent to the middle and lower lobes of the right lung, the pericardium and the diaphragm. The tumor was completely resected, along with partial resection of the adherent tissues. The histological diagnosis was spindle cell sarcoma and the final diagnosis was MPNST of the anterior mediastinum, based on the characteristic microscopic appearance indicating the nervous origin of the tumor and on the intraoperative findings. The patient remains free of recurrence 1 year after surgery.


Long non-coding RNA LINK-A promotes glioma cell growth and invasion via lactate dehydrogenase A.
Long non-coding RNAs (lncRNAs) have recently been identified in mammals as new modulators of cancer origin and progression participating in various cellular pro-cesses. Long intergenic non-coding RNA for kinase activation (LINK-A), belonging to one of the intergenic lncRNAs, was reported to regulate signaling pathways correlated with triple-negative breast cancer. However, the expression and the functional role of LINK-A in glioma are still unclear. In the present study, we demonstrated that LINK-A was upregulated in human glioma cells compared with the expression noted in normal astrocytes. Knockdown of LINK-A inhibited cell proliferation, migration and invasion in U87 and U251 glioma cells. In addition, we found that lactate dehydrogenase A (LDH-A) was regulated by LINK-A, and enforced expression of LDH-A promoted glycolysis and proliferation in glioma cells. More importantly, we found that LDH-A was involved in the LINK-A-mediated proliferation and invasion of glioma cells. Collectively, these results provide new evidence of an important role for LINK-A in the development of glioma.


The series RE5Li2Sn7 (RE = Ce, Pr, Nd, Sm) revisited: crystal structure of RE5Li2-xSn7+x [0 ≤ x ≤ 0.03 (1)].
The series of RE5Li2Sn7 (RE = Ce-Sm) compounds were synthesized by high-temperature reactions and structurally characterized by single-crystal X-ray diffraction. The compounds are pentacerium dilithium heptastannide, Ce5Li1.97Sn7.03, pentapreseodymium dilithium heptastannide, Pr5Li1.98Sn7.02, pentaneodymium dilithium heptastannide, Nd5Li1.99Sn7.01, and pentasamarium dilithium heptastannide, Sm5Li2Sn7. All five compounds crystallize in the chiral orthorhombic space group P212121 (No. 19), which is relatively uncommon among intermetallic phases. The structure belongs to the Ce5Li2Sn7 structure type (Pearson symbol oP56), with 14 unique atoms in the asymmetric unit. Minor compositional variations exist, due to the mixed occupancy of Li and Sn atoms at one of the Li sites. The small occupational disorder is most evident for RE5Li2-xSn7+x (RE = Ce, Pr; x ≃ 0.03), while the structure of Nd5Li2Sn7 and Sm5Li2Sn7 show no apparent disorder.


The Presence of Vacuolated Kupffer Cells Raises a Clinical Suspicion of Niemann-Pick Disease Type C in Neonatal Cholestasis.
Early diagnosis of Niemann-Pick disease type C (NP-C) in neonatal cholestasis is still challenging because splenomegaly is non-specific and oxysterol profiling studies also have a relatively low specificity. This study explores a method for identifying infants with a high clinical suspicion of NP-C in neonatal cholestasis. We reviewed the clinical findings of 9 neonatal cholestatic infants with NP-C genetically diagnosed between January 2015 and December 2020. Seven underwent liver biopsy at ages ranging from 35 to 112 d. Foam cells were only detected in 2 (28.6%, 2/7) liver tissues obtained beyond 3 months of age. However, vacuolated Kupffer cells were detected in all 7 liver tissues. Their significance was explored by using 168 neonatal cholestatic infants, who underwent genetic tests and liver biopsy between January 2018 and December 2020. Of them, 26 detected vacuolated Kupffer cells. Six (23.1%, 6/26) were diagnosed as NP-C, comparing to none of the 142 neonatal cholestatic infants without vacuolated Kupffer cells (χ 2 = 33.983, p < 0.001). The ratio of positive diagnosis of NP-C was 31.6% (6/19) in neonatal cholestatic infants with both vacuolated Kupffer cells and splenomegaly. Therefore, we conclude that the presence of vacuolated Kupffer cells can raise a high clinical suspicion of NP-C in neonatal cholestatic infants, especially in those with splenomegaly.


Chemistry of lipid peroxidation.
The free radical chemistry of lipid peroxidation is complex. The classical mechanism of autoxidation involving a peroxy radical abstracting hydrogen atom from lipid and oxygen addition to the carbon radical thus formed must be modified to include (1) peroxy radical beta fragmentation and (2) peroxy radical cyclization. A host of diene hydroperoxides, cyclic peroxides, bicyclic peroxides and epoxy alcohols may be formed in free fatty acid or phospholipid autoxidation. The distribution of products and the effects of hydrogen atom donors on product distribution are understandable by referring to a general scheme for autoxidation described in Scheme III and in Ref. 10.


Combined staged anterior and posterior correction and fusion of the spine in scoliosis following poliomyelitis.
The problems with severe forms of scoliosis following poliomyelitis include the associated muscle imbalance, soft tissue contractures and pelvic obliquity. Such deformities militate against optimal correction and maintenance of that correction and their treatment is often marred by pseudarthroses. Seventeen patients with an average curve of 93 degrees have been treated and followed for up to 38 months. Preliminary traction was used in 8 patients, then a staged anterior and posterior correction and fusion was done, using Dwyer's instrumentation of the major curve in all and a Harrington rod to supplement the posterior fusion in eleven patients. With this technique the major curve was corrected by 80 per cent with an average 2 per cent loss over 18 months. No pseudarthroses were seen when the Harrington rod was used. Great care must be taken if halo-pelvic traction is to be used for patients with pelvic obliquity, for preliminary correction halo-femoral traction will often be adequate. In the more severe forms of paralytic scoliosis a combined staged anterior and posterior correction and fusion should be considered if the aim is maximal correction of the scoliosis and avoidance of pseudarthroses.