Thiophilic interaction chromatography (TIC) of amyloid-beta protein precursor.
Neuritic plaques, one of the diagnostic characteristics of an AD, contain extracellular deposits of amyloid-beta (Abeta) derived from amyloid-beta protein precursor (AbetaPP). The objective of this study was to extract AbetaPP out of HEK293 cells and to purify it. Two procedures were chosen for purification of AbetaPP: Thiophilic Interaction Chromatography (TIC) and molecular sieving. Using Superdex 75, Superose 12, and Fractogel gel matrices, AbetaPP was isolated on HPLC. The chromatograms illustrate the purification of AbetaPP. Our method describes a new and elegant way for the extraction and purification of AbetaPP from HEK293 cell lines using thiophilic interaction chromatography (TIC).


Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study.
We investigated the efficacy of a Wilms' tumor gene 1 (WT1) vaccine combined with gemcitabine (GEMWT1) and compared it with gemcitabine (GEM) monotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II study. We randomly assigned HLA-A*02:01- or HLA-A*24:02-positive patients with advanced PDAC to receive GEMWT1 or GEM. We assessed WT1-specific immune responses via delayed-type hypersensitivity (DTH) to the WT1 peptide and a tetramer assay to detect WT1-specific cytotoxic T lymphocytes (WT1-CTL). Of 91 patients enrolled, 85 were evaluable (GEMWT1: n = 42; GEM: n = 43). GEMWT1 prolonged progression-free survival [PFS; hazard ratio (HR), 0.66; P = 0.084] and improved overall survival rate at 1 year (1-year OS%; GEMWT1: 35.7%; GEM: 20.9%). However, the difference in OS was not significant (HR: 0.82; P = 0.363). These effects were particularly evident in metastatic PDAC (PFS: HR 0.51, P = 0.0017; 1-year OS%: GEMWT1 27.3%; GEM 11.8%). The combination was well tolerated, with no unexpected serious adverse events. In patients with metastatic PDAC, PFS in the DTH-positive GEMWT1 group was significantly prolonged, with a better HR of 0.27 compared with the GEM group, whereas PFS in the DTH-negative GEMWT1 group was similar to that in the GEM group (HR 0.86; P = 0.001). DTH positivity was associated with an increase in WT1-CTLs induced by the WT1 vaccine. GEM plus the WT1 vaccine prolonged PFS and may improve 1-year OS% in advanced PDAC. These clinical effects were associated with the induction of WT1-specific immune responses. Cancer Immunol Res; 6(3); 320-31. ©2018 AACR.


Whole-Body Characterization of Estrogen Receptor Status in Metastatic Breast Cancer with 16α-18F-Fluoro-17β-Estradiol Positron Emission Tomography: Meta-Analysis and Recommendations for Integration into Clinical Applications.
Estrogen receptor (ER) status by immunohistochemistry (IHC) of cancer tissue is currently used to direct endocrine therapy in breast cancer. Positron emission tomography (PET) with 16α-18F-fluoro-17β-estradiol (18 F-FES) noninvasively characterizes ER ligand-binding function of breast cancer lesions. Concordance of imaging and tissue assays should be established for 18 F-FES PET to be an alternative or complement to tissue biopsy for metastatic lesions. We conducted a meta-analysis of published results comparing 18 F-FES PET and tissue assays of ER status in patients with breast cancer. PubMed and EMBASE were searched for English-language manuscripts with at least 10 patients and low overall risk of bias. Thresholds for imaging and tissue classification could differ between studies but had to be clearly stated. We used hierarchical summary receiver-operating characteristic curve models for the meta-analysis. The primary analysis included 113 nonbreast lesions from 4 studies; an expanded analysis included 327 total lesions from 11 studies. Treating IHC results as the reference standard, sensitivity was 0.78 (95% confidence region 0.65-0.88) and specificity 0.98 (0.65-1.00) for the primary analysis of nonbreast lesions. In the expanded analysis including non-IHC tissue assays and all lesion sites, sensitivity was 0.81 (0.73-0.87) and specificity 0.86 (0.68-0.94). These results suggest that 18 F-FES PET is useful for characterization of ER status of metastatic breast cancer lesions. We also review current best practices for conducting 18 F-FES PET scans. This imaging assay has potential to improve clinically relevant outcomes for patients with (historically) ER-positive metastatic breast cancer, including those with brain metastases and/or lobular histology. IMPLICATIONS FOR PRACTICE: 16α-18F-fluoro-17β-estradiol positron emission tomography (18 F-FES PET) imaging assesses estrogen receptor status in breast cancer in vivo. This work reviews the sensitivity and specificity of 18 F-FES PET in a meta-analysis with reference tissue assays and discusses best practices for use of the tracer as an imaging biomarker. 18 F-FES PET could enhance breast cancer diagnosis and staging as well as aid in therapy selection for patients with metastatic disease. Tissue sampling limitations, intrapatient heterogeneity, and temporal changes in molecular markers make it likely that 18 F-FES PET will complement existing assays when clinically available in the near future.


Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement.
Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966. Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes. The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients. GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients. GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology.


Influence of lamina vastoadductoria dissection on the outcomes of femoral artery extensive lesion stenting: A pilot randomised investigation.
Aim of the study was to improve the immediate and long-term results of stenting of the superficial femoral artery in extended lesions with the changing of the biomechanics of superficial ffemoral artery and of the first portion of the popliteal artery. Pilot randomized prospective single-center study were included 70 patients. Patients were randomized into two groups in 1 × 1 format for 35 people using the envelope method. Self-expanding bare metal stents were used in all cases. At the first group standard revascularization procedures with SFA stenting were performed; in the second group, the superficial femoral artery stenting was supplemented with fasciotomy in the Hunter's canal with the superficial femoral artery intersection. The total observation period was 2 years. During the observation period an assessment of the clinical symptoms of the lower extremities, measurement of the ankle-brachial index and ultrasound duplex scanning of the operated segment were performed. All procedures in both groups were successfully performed. Primary patency through 24 months was 28.5% (10 of 35) in group 1 and 60% (21 of 35) in group 2 (p = 0,015). Changing the biomechanical properties of the distal of the superficial femoral artery segment and of the first portion of the popliteal artery is safe and contributes to the primary patency improvement during the stenting of extended of the superficial femoral artery lesions compared to standard SFA stenting. Dissection of the lamina vastoadductoria with transection of the collateral branches of the knee joint network reduces frequent and severe damages of stents after the stenting of the superficial femoral artery extended lesion. According to the frequency of complications in the early and mid-term postoperative period, limb salvage, mortality and the secondary patency rates, the new method is comparable with standard of the superficial femoral artery stenting.


Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.
Novel esters of non steroidal anti-inflammatory drugs, α-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders.


Cochlear implantation as a durable tinnitus treatment in single-sided deafness.
Severe tinnitus can seriously impair patients in their activities in daily life and reduce their quality of life. The aims of this prospective clinical study were to assess the long-term effects of cochlear implantation (CI) on tinnitus in patients with single-sided deafness and ipsilateral incapacitating tinnitus, and to investigate whether CI could treat various types of tinnitus. Twenty-six subjects with unilateral severe-to-profound sensorineural hearing loss received a CI. Patients suffered from severe tinnitus greater than 6/10 on a visual analogue scale (VAS) due to unilateral deafness. Assessment consisted of a tinnitus analysis including determination of tinnitus type, frequency, and loudness. A tinnitus questionnaire (TQ) measured tinnitus distress. VAS and TQ were administered pre-implantation and post-implantation. All 26 patients reported a subjective benefit from CI. Tinnitus loudness reduced significantly after CI from 8.6 to 2.2 on the VAS (scale: 0-10). The TQ total score decreased significantly and the mean tinnitus degree decreased from severe to mild. No differences were observed between patients with pure-tone tinnitus, narrow band noise tinnitus, or polyphonic tinnitus. The degree of tinnitus loudness reduction remained stable after CI. CI can successfully be used as treatment of severe tinnitus in patients with single-sided deafness and is equally effective for pure tone, narrow band noise, and polyphonic tinnitus. Long-term results show that implantation provides durable tinnitus relief in these patients. These results support the hypothesis that physiopathological mechanisms after peripheral deafferentation are reversible when hearing is restored. Single-sided deafness accompanied by severe tinnitus is a new indication for CI.


Diagnosis Prediction from Electronic Health Records Using the Binary Diagnosis History Vector Representation.
Large amounts of rich, heterogeneous information nowadays routinely collected by healthcare providers across the world possess remarkable potential for the extraction of novel medical data and the assessment of different practices in real-world conditions. Specifically in this work, our goal is to use electronic health records (EHRs) to predict progression patterns of future diagnoses of ailments for a particular patient, given the patient's present diagnostic history. Following the highly promising results of a recently proposed approach that introduced the diagnosis history vector representation of a patient's diagnostic record, we introduce a series of improvements to the model and conduct thorough experiments that demonstrate its scalability, accuracy, and practicability in the clinical context. We show that the model is able to capture well the interaction between a large number of ailments that correspond to the most frequent diagnoses, show how the original learning framework can be adapted to increase its prediction specificity, and describe a principled, probabilistic method for incorporating explicit, human clinical knowledge to overcome semantic limitations of the raw EHR data.


Carbonic anhydrase inhibitors. Selective inhibition of human tumor-associated isozymes IX and XII and cytosolic isozymes I and II with some substituted-2-mercapto-benzenesulfonamides.
A series of 2-mercapto-substituted-benzenesulfonamides has been prepared by a unique two-step procedure starting from the corresponding 2-chloro-substituted benzenesulfonamides. Compounds bearing an unsubstituted mercapto group and the corresponding S-benzoyl derivatives were investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 126.96.36.199), i.e., the cytosolic, ubiquitous isozymes CA I and II, as well as the transmembrane, tumor associated isozymes CA IX and XII. These derivatives were medium potency hCA I inhibitors (K(I)s in the range of 1.5-5.7 microM), two derivatives were strong hCA II inhibitors (K(I)s in the range of 15-16 nM), whereas the others showed weak activity. These compounds inhibited hCA IX with inhibition constants in the range 160-1950 nM and hCA XII with inhibition constants in the range 1.2-413 nM. Some of these derivatives showed a certain degree of selectivity for inhibition of the tumor-associated over the cytosolic isoforms, being thus interesting leads for the development of potentially novel applications in the management of hypoxic tumors which overexpress CA IX and XII.


Determining transcription factor activity from microarray data using Bayesian Markov chain Monte Carlo sampling.
Many biological processes rely on remodeling of the transcriptional response of cells through activation of transcription factors. Although determination of the activity level of transcription factors from microarray data can provide insight into developmental and disease processes, it requires careful analysis because of the multiple regulation of genes. We present a novel approach that handles both the assignment of genes to multiple patterns, as required by multiple regulation, and the linking of genes in prior probability distributions according to their known transcriptional regulators. We demonstrate the power of this approach in simulations and by application to yeast cell cycle and deletion mutant data. The results of simulations in the presence of increasing noise showed improved recovery of patterns in terms of chi2 fit. Analysis of the yeast data led to improved inference of biologically meaningful groups in comparison to other techniques, as demonstrated with ROC analysis. The new algorithm provides an approach for estimating the levels of transcription factor activity from microarray data, and therefore provides insights into biological response.


Metastatic seminoma in the duodenum: diagnosis with endoscopy followed by successful treatment.
Seminomas rarely metastasize to the gastrointestinal tract. In general, these lesions metastasize to the lungs or retroperitoneal lymph nodes. A 34-year-old Japanese man who had undergone orchiectomy for seminoma two years earlier experienced shortness of breath and tarry stools. The patient presented at our hospital and was diagnosed with metastatic seminoma to the third portion of the duodenum on double balloon endoscopy. He was effectively treated with chemotherapy and continues to progress well, with no episodes of recurrence.


Combinatorial interactions between viral proteins expand the potential functional landscape of the tomato yellow leaf curl virus proteome.
Viruses manipulate the cells they infect in order to replicate and spread. Due to strict size restrictions, viral genomes have reduced genetic space; how the action of the limited number of viral proteins results in the cell reprogramming observed during the infection is a long-standing question. Here, we explore the hypothesis that combinatorial interactions may expand the functional landscape of the viral proteome. We show that the proteins encoded by a plant-infecting DNA virus, the geminivirus tomato yellow leaf curl virus (TYLCV), physically associate with one another in an intricate network, as detected by a number of protein-protein interaction techniques. Importantly, our results indicate that intra-viral protein-protein interactions can modify the subcellular localization of the proteins involved. Using one particular pairwise interaction, that between the virus-encoded C2 and CP proteins, as proof-of-concept, we demonstrate that the combination of viral proteins leads to novel transcriptional effects on the host cell. Taken together, our results underscore the importance of studying viral protein function in the context of the infection. We propose a model in which viral proteins might have evolved to extensively interact with other elements within the viral proteome, enlarging the potential functional landscape available to the pathogen.


MITF accurately highlights epidermal melanocytes in atypical intraepidermal melanocytic proliferations.
Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P < 0.001) higher for Melan-A compared with hematoxylin and eosin staining. Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P < 0.001) fewer melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF.


[Technique of PCR-ACRS for the detection of CYP21 gene mutations].
To establish a rapid method of detecting CYP21 gene mutations. Fifty Chinese patients with 21-hydroxylase deficiency and some of their families were investigated. Blood samples were obtained for extraction of peripheral blood lymphocytes. A search for restriction sites discriminating between the morbid and the normal in CYP21 gene was made by the computer program DNAssist. PCR-based amplication-created restriction site(PCR-ACRS) was performed at I172N and R356W which are not natural recognition sequence. In addition, I172N and R356W were analysed in five families which conform to the applicability of PCR-ACRS. In 50 identified 21-hydroxylase deficient Chinese patients, 21 were found to have I172 N (3 were homozygote, 18 were heterozygote); 8 were found to have R356W, all of them were heterozygote. By analysing the families, the findings were consistent with the characteristics of autosomal recessive genetic deficiency. Analysis of CYP21 gene point mutations using PCR-ACRS is relatively simple, accurate and feasible.


Reporting occupational violence in emergency departments.
A study has revealed that emergency department (ED) staff across all roles receive verbal abuse from patients, but that nurses are more likely to be physically assaulted and are less likely to feel safe.


[Platelet polymorphism and coronary artery disease].
Several publications over the last ten years have addressed the problem of genetic mutation coding platelet membrane glycoproteins and thrombotic arterial disease. The principal polymorphisms studied are those of glycoproteins GPIIIa, GPIb and the GPIa-IIa complex. The relationships of each of these polymorphisms and myocardial infarction or coronary artery disease are reported and are often subject to controversy. The polymorphism PLA2 of the GPIIIa has been shown to be a risk factor for infarction in young people, especially when associated with cigarette smoking. Its role in triggering myocardial infarction or in the severity of coronary artery disease is not so clear in the general population. Two types of polymorphism concerning the GPIb and that of the GPIa-IIa complex should also predispose to early coronary thrombotic complications. In addition, the study of these platelet polymorphisms gives a better insight into individual sensitivity to platelet antiaggregant therapy.


Host-cell cyclophilin is important for the intracellular replication of Leishmania major.
The antiparasitic effects of cyclosporin A were examined in leishmanial infection by analysing the role of CsA-binding proteins (cyclophilins) in the host-parasite interaction. We hypothesized that the leishmanicidal effects of CsA on Leishmania major infected macrophages might be mediated through a cyclophilin of either the parasite or the host cell. Two cyclophilins (20 and 22 kDa) were purified from L. major parasites and N-terminally sequenced. Although enzyme activity of these cyclophilins was inhibited by CsA, pretreatment of L. major parasites with CsA did not result in reduction of a subsequent macrophage infection, arguing against a role of L. major cyclophilins as infectivity potentiators. However, host-cell cyclophilin A (CypA) was found to be critically involved in the intracellular replication of L. major parasites in murine macrophages. An antisense oligonucleotide to murine CypA was constructed and added to cultures of peritoneal macrophages prior to infection with L. major parasites. This treatment strongly reduced the expression of CypA in macrophages and resulted in the inhibition of the intracellular replication of L. major amastigotes. These data indicate that interaction of amastigotes with host-cell cyclophilin is an important part of the intracellular replication machinery of L. major and define, for the first time, a direct involvement of a cyclophilin in the survival strategies of an intracellular parasite.


Health risks of heavy metal contamination in road surface dusts from selected major roads in East London, South Africa.
The study assessed the concentration and health hazards of Cd, Mn, Pb, Ni and Zn in 54 road surface dust samples. Heavy metal concentrations descended as follows: Mn > Zn > Pb > Ni > Cd and the concentrations were 316.22, 161.24, 88.76, 22.69 and 0.21. Health hazard assessment showed that the modes of exposure descended in the sequence of ingestion > dermal contact > inhalation for children and dermal contact > ingestion > inhalation for adults. The hazard index for both populations was >1 suggesting susceptibility to non-cancer risks. The carcinogenic risk for Ni and Cd was below 1 × 10-4 suggesting a negligible risk of cancer for both populations. The study suggests that more research studies on HM contamination in road dusts are to be undertaken in the country to develop HM pollution threshold values in road dusts and to account for pollution in city centers.


Effects of glucose-lowering agents on ischemic stroke.
Diabetes mellitus (DM) is a major risk factor for cardiovascular events, including ischemic stroke. Moreover, ischemic stroke appears to be more severe in these patients and to be associated with less favorable outcomes. However, strict glycemic control does not appear to reduce the risk of ischemic stroke. On the other hand, newer glucose-lowering agents (glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) reduced the risk of cardiovascular events in recent randomized, placebo-controlled trials. Semaglutide also reduced the risk of ischemic stroke. These benefits are independent of glucose lowering and might be due to the favorable effects of these agents on body weight and blood pressure. Pioglitazone also reduced the risk of recurrent stroke in patients with insulin resistance or type 2 DM but the unfavorable safety profile limits its use. In contrast, sulfonylureas and dipeptidyl peptidase 4 inhibitors have a neutral effect on cardiovascular morbidity and might be less attractive options in this high-risk population.


[Revisiting eponyms of arteries of the brain].
This article describes the eponymous terms in anatomical nomenclature of the cerebral arteries. There are historical references revealing the etymology of described eponyms, including information about the professional and personal life of doctors and scientists who had first discovered or described particular structure of the cerebral arterial network. Chronology of the discovery of the cerebral arterial circle is described in details. It is shown that some eponymous terms contain the names of several doctors who studied a particular medical issue simultaneously, which is a reflection of the stages of the medical science development and the evidence of the continuity of scientific knowledge.


Sirtuin 3 and mitochondrial permeability transition pore (mPTP): A systematic review.
Mitochondrial permeability transition pore (mPTP) is a channel that opens at the inner mitochondrial membrane under conditions of stress. Sirtuin 3 (Sirt3) is a mitochondrial deacetylase known to play a major role in stress resistance and a regulatory role in cell death. This systematic review aims to elucidate the role of Sirt3 in mPTP inhibition. Electronic databases, including PubMed, EMBASE, Web of Science and Cochrane Library were searched up to May 2020. Original studies that investigated the relationship between Sirt3 and mPTP were included. Two reviewers independently extracted data on study characteristics, methods and outcomes. A total of 194 articles were found. Twenty-nine articles, which met criteria were included in the systematic review. Twenty-three studies provided evidence of the inhibitory effect of Sirt3 on the mPTP aperture. This review summarizes up-to-date evidence of the protective and inhibitory role of Sirt3 through deacetylating Cyclophilin D (CypD) on the mPTP aperture. Furthermore, we discuss the implications of this effect in disease.


Magnetic field effects as a result of the radical pair mechanism are unlikely in redox enzymes.
Environmental exposure to electromagnetic fields is potentially carcinogenic. The radical pair mechanism is considered the most feasible mechanism of interaction between weak magnetic fields encountered in our environment and biochemical systems. Radicals are abundant in biology, both as free radicals and reaction intermediates in enzyme mechanisms. The catalytic cycles of some flavin-dependent enzymes are either known or potentially involve radical pairs. Here, we have investigated the magnetic field sensitivity of a number of flavoenzymes with important cellular roles. We also investigated the magnetic field sensitivity of a model system involving stepwise reduction of a flavin analogue by a nicotinamide analogue-a reaction known to proceed via a radical pair. Under the experimental conditions used, magnetic field sensitivity was not observed in the reaction kinetics from stopped-flow measurements in any of the systems studied. Although widely implicated in radical pair chemistry, we conclude that thermally driven, flavoenzyme-catalysed reactions are unlikely to be influenced by exposure to external magnetic fields.


Combined treatment with low-dose cyclosporine and calcipotriol/betamethasone dipropionate ointment for moderate-to-severe plaque psoriasis: a randomized controlled open-label study.
Combination therapy is a common approach to psoriasis, aimed at improving clinical response and minimizing the risk of side effects. The aim of this pilot randomized open-label study was to evaluate the efficacy and safety of the combination of low-dose cyclosporine (CsA) with calcipotriol-betamethasone dipropionate (CBD) ointment in the treatment of psoriasis. Sixty patients with moderate-to-severe plaque psoriasis were randomized to receive CsA, 2 mg/kg/day, combined with CBD ointment (n = 30) or CsA, at the same daily dosage, in combination with an emollient (n = 30), for 8 weeks. The primary efficacy parameter was the Psoriasis Area and Severity Index (PASI) 75 response rate at 8 weeks. Combination therapy with CsA and CBD ointment was more effective than CsA and emollient treatment, with statistically significant results, particularly less itching after 4 and 8 weeks and PASI reduction at all post-baseline visits. Significantly more patients treated with CsA + CBD achieved the PASI 75 at 8th week (87% vs 37% in the CsA-emollient group; p = 0.0001). The efficacy results were paralleled by the investigator and patient's global assessment of disease severity at the end of study. Our results suggest that the addition of CBD ointment to low-dose CsA enhances clinical response and improves the risk/benefit ratio.


Double-Layer Compressive Sensing Based Efficient DOA Estimation in WSAN with Block Data Loss.
Accurate information acquisition is of vital importance for wireless sensor array network (WSAN) direction of arrival (DOA) estimation. However, due to the lossy nature of low-power wireless links, data loss, especially block data loss induced by adopting a large packet size, has a catastrophic effect on DOA estimation performance in WSAN. In this paper, we propose a double-layer compressive sensing (CS) framework to eliminate the hazards of block data loss, to achieve high accuracy and efficient DOA estimation. In addition to modeling the random packet loss during transmission as a passive CS process, an active CS procedure is introduced at each array sensor to further enhance the robustness of transmission. Furthermore, to avoid the error propagation from signal recovery to DOA estimation in conventional methods, we propose a direct DOA estimation technique under the double-layer CS framework. Leveraging a joint frequency and spatial domain sparse representation of the sensor array data, the fusion center (FC) can directly obtain the DOA estimation results according to the received data packets, skipping the phase of signal recovery. Extensive simulations demonstrate that the double-layer CS framework can eliminate the adverse effects induced by block data loss and yield a superior DOA estimation performance in WSAN.


Identification of CD24 as a marker of Patched1 deleted medulloblastoma-initiating neural progenitor cells.
High morbidity and mortality are common traits of malignant tumours and identification of the cells responsible is a focus of on-going research. Many studies are now reporting the use of antibodies specific to Clusters of Differentiation (CD) cell surface antigens to identify tumour-initiating cell (TIC) populations in neural tumours. Medulloblastoma is one of the most common malignant brain tumours in children and despite a considerable amount of research investigating this tumour, the identity of the TICs, and the means by which such cells can be targeted remain largely unknown. Current prognostication and stratification of medulloblastoma using clinical factors, histology and genetic profiling have classified this tumour into four main subgroups: WNT, Sonic hedgehog (SHH), Group 3 and Group 4. Of these subgroups, SHH remains one of the most studied tumour groups due to the ability to model medulloblastoma formation through targeted deletion of the Shh pathway inhibitor Patched1 (Ptch1). Here we sought to utilise CD antibody expression to identify and isolate TIC populations in Ptch1 deleted medulloblastoma, and determine if these antibodies can help classify the identity of human medulloblastoma subgroups. Using a fluorescence-activated cell sorted (FACS) CD antibody panel, we identified CD24 as a marker of TICs in Ptch1 deleted medulloblastoma. CD24 expression was not correlated with markers of astrocytes or oligodendrocytes, but co-labelled with markers of neural progenitor cells. In conjunction with CD15, proliferating CD24+/CD15+ granule cell precursors (GCPs) were identified as a TIC population in Ptch1 deleted medulloblastoma. On human medulloblastoma, CD24 was found to be highly expressed on Group 3, Group 4 and SHH subgroups compared with the WNT subgroup, which was predominantly positive for CD15, suggesting CD24 is an important marker of non-WNT medulloblastoma initiating cells and a potential therapeutic target in human medulloblastoma. This study reports the use of CD24 and CD15 to isolate a GCP-like TIC population in Ptch1 deleted medulloblastoma, and suggests CD24 expression as a marker to help stratify human WNT tumours from other medulloblastoma subgroups.


The gap before real clinical application of imaging-based machine-learning and radiomic models for chemoradiation outcome prediction in esophageal cancer: a systematic review and meta-analysis.
Due to tumoral heterogeneity and the lack of robust biomarkers, the prediction of chemoradiotherapy response and prognosis in patients with esophageal cancer (EC) is challenging. The goal of this study was to assess the study quality and clinical value of machine learning and radiomic-based quantitative imaging studies for predicting the outcomes of EC patients after chemoradiotherapy. PubMed, Embase, and Cochrane were searched for eligible articles. The methodological quality and risk of bias were evaluated using the Radiomics Quality Score (RQS), Image Biomarkers Standardization Initiative (IBSI) Guideline, and Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement, as well as the modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. A meta-analysis of the evidence focusing on predicting chemoradiotherapy response and outcome in EC patients was implemented. Forty-six studies were eligible for qualitative synthesis. The mean RQS score was 9.07, with an adherence rate of 42.52%. The adherence rates of the TRIPOD and IBSI were 61.70 and 43.17%, respectively. Ultimately, 24 studies were included in the meta-analysis, of which 16 studies had a pooled sensitivity, specificity, and area under the curve (AUC) of 0.83 (0.76-0.89), 0.83 (0.79-0.86), and 0.84 (0.81-0.87) in neoadjuvant chemoradiotherapy datasets, as well as 0.84 (0.75-0.93), 0.89 (0.83-0.93), and 0.93 (0.90-0.95) in definitive chemoradiotherapy datasets, respectively. Moreover, radiomics could distinguish patients from the low-risk and high-risk groups with different disease-free survival (DFS) (pooled hazard ratio: 3.43, 95% CI 2.39-4.92) and overall survival (pooled hazard ratio: 2.49, 95% CI 1.91-3.25). The results of subgroup and regression analyses showed that some of the heterogeneity was explained by the combination with clinical factors, sample size, and usage of the deep learning (DL) signature. Noninvasive radiomics offers promising potential for optimizing treatment decision-making in EC patients. However, it is necessary to make scientific advancements in EC radiomics regarding reproducibility, clinical usefulness analysis, and open science categories. Improved model reporting of study objectives, blind assessment, and image processing steps are required to help promote real clinical applications of radiomics in EC research.


Role of surface oxides in the formation of solid-electrolyte interphases at silicon electrodes for lithium-ion batteries.
Nonaqueous solvents in modern battery technologies undergo electroreduction at negative electrodes, leading to the formation of a solid-electrolyte interphase (SEI). The mechanisms and reactions leading to a stable SEI on silicon electrodes in lithium-ion batteries are still poorly understood. This lack of understanding inhibits the rational design of electrolyte additives, active material coatings, and the prediction of Li-ion battery life in general. We prepared SEI with a common nonaqueous solvent (LiPF6 in PC and in EC/DEC 1:1 by wt %) on silicon oxide and etched silicon (001) surfaces in various states of lithiation to understand the role of surface chemistry on the SEI formation mechanism and SEI structure. Anhydrous and anoxic techniques were used to prevent air and moisture contamination of prepared SEI films, allowing for more accurate characterization of SEI chemical stratification and composition by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) depth profiling. Additionally, multivariate statistical methods were used to better understand TOF-SIMS depth profiling studies. We conclude that the absence of native-oxide layer on silicon has a significant impact on the formation, composition, structure, and thickness of the SEI.


Long-Term Care: Safe Drug Handling of Oral Chemotherapy.
Many oral chemotherapy agents have been approved over the last 15 years and are displacing or augmenting parenteral chemotherapy. As 8,000 Baby Boomers turn 65 years of age every day, more elders will migrate to long-term care and assisted living facilities, and consultant pharmacists may need to manage chemotherapy for the first time. Though many therapeutic classes of oral drugs are hazardous, the majority of oral chemotherapy agents are hazardous by virtue of their mechanisms of action. Previous hazardous drug-handling recommendations from the Occupational Safety and Health Administration, the National Institute of Occupational Safety and Health, the American Society of Health-System Pharmacists, the American Society of Clinical Oncology, the Hematology/Oncology Pharmacy Association, and the Oncology Nursing Society have matured into new standards from the United States Pharmacopeial Convention (USP), Chapter <800>, "Hazardous Drugs-Handling in Health Care Settings." These standards provide a comprehensive approach for safe drug handling across all health care settings and underscore the need for consultant pharmacist involvement in nursing and assisted living facilities.


Quantitative modeling of gene expression using DNA shape features of binding sites.
Prediction of gene expression levels driven by regulatory sequences is pivotal in genomic biology. A major focus in transcriptional regulation is sequence-to-expression modeling, which interprets the enhancer sequence based on transcription factor concentrations and DNA binding specificities and predicts precise gene expression levels in varying cellular contexts. Such models largely rely on the position weight matrix (PWM) model for DNA binding, and the effect of alternative models based on DNA shape remains unexplored. Here, we propose a statistical thermodynamics model of gene expression using DNA shape features of binding sites. We used rigorous methods to evaluate the fits of expression readouts of 37 enhancers regulating spatial gene expression patterns in Drosophila embryo, and show that DNA shape-based models perform arguably better than PWM-based models. We also observed DNA shape captures information complimentary to the PWM, in a way that is useful for expression modeling. Furthermore, we tested if combining shape and PWM-based features provides better predictions than using either binding model alone. Our work demonstrates that the increasingly popular DNA-binding models based on local DNA shape can be useful in sequence-to-expression modeling. It also provides a framework for future studies to predict gene expression better than with PWM models alone.


Aspergillus derived mycotoxins in food and the environment: Prevalence, detection, and toxicity.
Aspergillus species are the paramount ubiquitous fungi that contaminate various food substrates and produce biochemicals known as mycotoxins. Aflatoxins (AFTs), ochratoxin A (OTA), patulin (PAT), citrinin (CIT), aflatrem (AT), secalonic acids (SA), cyclopiazonic acid (CPA), terrein (TR), sterigmatocystin (ST) and gliotoxin (GT), and other toxins produced by species of Aspergillus plays a major role in food and human health. Mycotoxins exhibited wide range of toxicity to the humans and animal models even at nanomolar (nM) concentration. Consumption of detrimental mycotoxins adulterated foodstuffs affects human and animal health even trace amounts. Bioaerosols consisting of spores and hyphal fragments are active elicitors of bronchial irritation and allergy, and challenging to the public health. Aspergillus is the furthermost predominant environmental contaminant unswervingly defile lives with a 40-90 % mortality risk in patients with conceded immunity. Genomics, proteomics, transcriptomics, and metabolomics approaches useful for mycotoxins' detection which are expensive. Antibody based detection of toxins chemotypes may result in cross-reactivity and uncertainty. Aptamers (APT) are single stranded DNA (ssDNA/RNA), are specifically binds to the target molecules can be generated by systematic evolution of ligands through exponential enrichment (SELEX). APT are fast, sensitive, simple, in-expensive, and field-deployable rapid point of care (POC) detection of toxins, and a better alternative to antibodies.


[Pregnane X receptor promotes programmed cell death protein 4 expression in HepG2 cells].
To investigate the role of pregnane X receptor (PXR) in the regulation of programmed cell death proteins (PDCDs) in HepG2 cells and explore the underlying molecular mechanism. HepG2 cells were treated with PXR agonist rifampicin (10 μmol/L) or SR12813 (1 μmol/L) for 24 h, using DMSO as the negative control. HepG2 cells were infected with constitutively activated PXR adenovirus (VP-PXR) for 36 h, with the cells infected with Mock as the negative control. The mRNA levels of PDCD2, PDCD4, PDCD5, and PDCD6 and the expression of miRNA21 were detected using qRT-PCR, and the protein level of PDCD4 was detected with Western blotting. Bioinformatic analysis was performed to predict the potential PXRresponsive elements (PXREs) motifs in the promotor region of human PDCD4. The expressions of PDCD5 and PDCD6 mRNA did not differ significantly between rifampicin-treated and the control cells, while PDCD4 mRNA expression increased (t=4.209, P=0.008) and PDCD2 mRNA decreased significantly (t=-2.875, P=0.017) in rifampicin-treated cells. The mRNA expressions of PDCD2, PDCD5 and PDCD6 showed no significant difference between SR12813-treated cells and the control cells, while PDCD4 mRNA expression increased obviously in SR12813-treated cells (t=4.574, P=0.006). The PXR target gene MDR1 also increased significantly in the rifampicin- and SR12813-treated cells compared with the control cells (P=0.020 and 0.01, respectively). Infection of the cells with VP-PXR adenovirus resulted in significantly increased expression of PDCD4 and MDR1 mRNA as compared with Mock group (t=3.343, P=0.000; t=3.343, P=0.024, respectively) without causing obvious changes in PDCD2 and PDCD6 mRNA expressions. The protein level of PDCD4 increased significantly in both rifampicin (t= 2.779, P=0.025) group and VP- PXR group (t=3.066, P=0.012). The expression of miRNA21, the negative regulatory factor of PDCD4, did not differ significantly between PXR agonist group and the control group. Informatic analysis revealed the presence of putative PXREs in the 5'-flanking region of PDCD4 gene. Our findings demonstrate that PXR agonism in HepG2 cells increases the expression of PDCD4, which is independent of miRNA21 pathway, and PDCD4 may be a target gene of PXR in HepG2 cells.


[Results of anterior levator and externus-plasty in idiopathic anorectal incontinence. A prospective manometric, electromyography and radiology study].
A prospective clinical manometric and radiological study has been performed, before and after anterior levatorplasty and sphincter plication on 18 patients (mean age 61.6 years) with neurogenic faecal incontinence. Continence was improved on 15 (83%) patients, 13 (72%) patients were continent to solid and liquid stool, 3 (17%) of whom regained normal continence only, at a minimum of 6 months follow-up (phi 21.5 months). Postoperatively there was a significant increase in the resting anal pressure (p = 0.05) an maximum voluntary contraction pressure (p = 0.001). No significant change in sphincter length, duration of the action potentials, pudendal nerve terminal motor latency (PNTML), pelvic descent or anorectal angle was seen postoperatively. The incontinence and defaecation-score showed postoperatively a significant difference concerning soiling, time from urgency to defaecation, and discrimination between flatus and stool.


From relative to absolute quantification of tryptic peptides with tandem mass tags: application to cerebrospinal fluid.
Quantification is a major task in proteomics. Among the different analytical strategies to enable peptide and protein quantification, tagging with isotopic labels has emerged as a practical, versatile, and efficient alternative. In particular, isobaric labels, such as TMT or iTRAQ, are now widely employed to make relative comparison of the protein amounts in separate biological samples with tandem mass spectrometry (MS/MS). We used herein a shotgun proteomic approach based on labelling with tandem mass tags (TMTs) for the relative quantification of proteins, and the absolute quantification of their tryptic peptides in human cerebrospinal fluid (CSF). First, the comparison of ante- and post-mortem CSF samples was carried out for the discovery of protein marker candidates of brain-damage disorders. Second, tryptic peptides representative of these candidates were measured in CSF using reporter-ion calibration curves. These works highlighted the advantages and limitations of such strategies for quantification purposes in proteomics.


Automatic internal calibration in liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry of protein digests.
Accurately measured peptide masses can be used for large-scale protein identification from bacterial whole-cell digests as an alternative to tandem mass spectrometry (MS/MS) provided mass measurement errors of a few parts-per-million (ppm) are obtained. Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) routinely achieves such mass accuracy either with internal calibration or by regulating the charge in the analyzer cell. We have developed a novel and automated method for internal calibration of liquid chromatography (LC)/FTICR data from whole-cell digests using peptides in the sample identified by concurrent MS/MS together with ambient polydimethylcyclosiloxanes as internal calibrants in the mass spectra. The method reduced mass measurement error from 4.3 +/- 3.7 ppm to 0.3 +/- 2.3 ppm in an E. coli LC/FTICR dataset of 1000 MS and MS/MS spectra and is applicable to all analyses of complex protein digests by FTICRMS.


Marginal donors and organ shortness: concomitant surgical procedures during heart transplantation: a literature review.
Heart transplantation represents the gold standard for end-stage heart failure. However, due to the increasing demand and the shortage of available organs, donor supply remains the main limitation. Marginal donor hearts in high-risk candidates who do not meet standard listing criteria are the only alternative when life expectancy is limited, but their use is still debated. Surgical correction of detected coronary lesions or valvular heart defects allows further enlargement of the number of available organs. In this article, we offer a literature review on this topic and report two marginal donor hearts with angiography evidence of coronary stenosis and preserved ventricular function, which underwent concomitant myocardial revascularization during heart implantation.


Antegrade placement of JJ catheter in the treatment of malignant ureteral obstruction: Retrospective analysis of a single centre.
The aim of the present study was to examine the results of antegrade JJ stent placement in upper urinary tract obstruction in patients where retrograde placement was not possible. In this retrospective study, patients who underwent antegrade JJ stent placement for malignant ureteral obstruction in the urology clinic of a university hospital between January 1, 2018 and December 31, 2020 were included in the study. JJ stent was placed under local or general anaesthesia guided by ultrasonography and fluoroscopy. Age, gender, kidney function values, pathologies causing obstruction, and complications of the patients were examined. In this study, 40 patients (16 men, 24 women) who underwent antegrade JJ stent placement were included. The mean ages of the women and men included were 51 (31-91) years and 62.5 (26-81) years, respectively. In all, antegrade JJ stenting was performed in 61 renal units of these patients. Of these, 21 were bilateral, 11 in the right collecting system and 8 in the left collecting systems. Clinical and technical success was achieved in 59 of the 61 procedures (96.6%). Arteriovenous fistula developed in only one patient, whereas no serious complications such as massive bleeding, resistant hematuria or pseudoaneurysm occurred in the remaining patients. The procedure was completed in a mean time of 15-30 minutes. Antegrade JJ stent placement is a procedure with a high success rate and low risk of complications that can be used in patients with severe ureteral obstruction owing to malignant or benign aetiologies. This method should be applied in centres experienced in malignant ureteral obstruction and on patients where retrograde placement was not possible. Furthermore, it should be considered as an alternative treatment option to open surgery as it can be performed under local anaesthesia in patients at a high risk of anaesthesia.


MECHANISM OF SELECTION FAVORING A WIDE TUBULAR COROLLA IN CAMPANULA PUNCTATA.
A previous study of Campanula punctata pollinated by Bombus diversus showed greater male reproductive success in plants with wider corollas when male reproductive success was measured by paternity analysis. Pollen removal alone was not a good measure of male reproductive success. The aim of the current study is to elucidate the mechanism underlying the selection on corolla width in C. punctata. Multiple regression analysis of male reproductive success in experimental populations revealed that the advantage of a wide corolla to the male is independent of the corolla width of pollen recipients, indicating that the position of pollen deposited on Bombus may not be an important factor for selection. However, the number of pollen grains that fell on the petal or off the flower and were lost at the first visit of Bombus (pollen fall) decreased with increasing corolla width, so that most pollen grains removed from a wide flower were deposited onto the pollinator. In a narrow flower, a greater proportion of the pollen removed was wasted through pollen fall. Pollen removal does not reflect male reproductive success, at least in part because of the loss of pollen in some flowers through pollen fall. The positive relationship between wider corollas and reduced loss of pollen through pollen fall is likely to lead to greater male reproductive success of wider flowers under repeated visits of pollinators. Decreased pollen fall, probably due to more gentle contact between pollen and bees in flowers with wider corollas, may be one of the mechanisms underlying the selection on corolla width of C. punctata.


Dissection and Isolation of Region-Specific Decellularized Lung Tissue.
Lung transplantation is often the only option for patients in the later stages of severe lung disease, but this is limited both due to the supply of suitable donor lungs and both acute and chronic rejection after transplantation. Ascertaining novel bioengineering approaches for the replacement of diseased lungs is imperative for improving patient survival and avoiding complications associated with current transplantation methodologies. An alternative approach involves the use of decellularized whole lungs lacking cellular constituents that are typically the cause of acute and chronic rejection. Since the lung is such a complex organ, it is of interest to examine the extracellular matrix components of specific regions, including the vasculature, airways, and alveolar tissue. The purpose of this approach is to establish simple and reproducible methods by which researchers may dissect and isolate region-specific tissue from fully decellularized lungs. The current protocol has been devised for pig and human lungs, but may be applied to other species as well. For this protocol, four regions of the tissue were specified: airway, vasculature, alveoli, and bulk lung tissue. This procedure allows for the procurement of samples of tissue that more accurately represent the contents of the decellularized lung tissue as opposed to traditional bulk analysis methods.


A Qualitative Study of Autistic Adults' Quality of Life During the COVID-19 Pandemic and Lockdowns.
Autistic people experience higher rates of most mental health conditions and report more difficulties with change than nonautistic people. As such, the periods of national stay-at-home orders (known in the United Kingdom as a "lockdown") endured since the beginning of the COVID-19 (coronavirus disease 2019) pandemic in March 2020 may have been particularly challenging for autistic people. This study explored autistic adults' experience of quality of life and well-being during the start of the COVID-19 pandemic (specifically March to August 2020) using open-text responses from an online survey. In total, 79 autistic adults from the United Kingdom (aged 21-75 years) took part. Participants completed an online survey, including open-text questions on how various factors influencing quality of life, such as social interactions, general health, well-being, and sensory experiences, were impacted by the COVID-19 pandemic and the first set of national lockdowns that occurred between March and August 2020. Thematic analysis created four key themes, each illustrated by several subthemes. These four themes explore (1) health, (2) social changes, (3) support provisions, and (4) adopting new routines. Many participants discussed the impact that the COVID-19 pandemic and the first set of national lockdowns had on their health and expressed concerns regarding the transition out of periods of lockdown, including readjusting to new rules, going back to in-person interactions, and reacclimatizing to high-stimulation sensory environments. However, several participants reported positive experiences of the periods of lockdown, such as reduced commuting, more control over sensory environments, and more time to pursue personal interests and self-care. These findings highlight the importance of giving autistic individuals the support they need to transition back to "normality" as COVID-19 becomes endemic.


The Representation of Motor (Inter)action, States of Action, and Learning: Three Perspectives on Motor Learning by Way of Imagery and Execution.
Learning in intelligent systems is a result of direct and indirect interaction with the environment. While humans can learn by way of different states of (inter)action such as the execution or the imagery of an action, their unique potential to induce brain- and mind-related changes in the motor action system is still being debated. The systematic repetition of different states of action (e.g., physical and/or mental practice) and their contribution to the learning of complex motor actions has traditionally been approached by way of performance improvements. More recently, approaches highlighting the role of action representation in the learning of complex motor actions have evolved and may provide additional insight into the learning process. In the present perspective paper, we build on brain-related findings and sketch recent research on learning by way of imagery and execution from a hierarchical, perceptual-cognitive approach to motor control and learning. These findings provide insights into the learning of intelligent systems from a perceptual-cognitive, representation-based perspective and as such add to our current understanding of action representation in memory and its changes with practice. Future research should build bridges between approaches in order to more thoroughly understand functional changes throughout the learning process and to facilitate motor learning, which may have particular importance for cognitive systems research in robotics, rehabilitation, and sports.


Recognizing and treating two types of long-term vasoconstriction in hypertension.
Long considered a single clinical entity, essential hypertension is now recognized as a heterogeneous spectrum of pathophysiologic disturbances, based on extensive clinical, pharmacologic and biochemical evidence. Two distinctly different mechanisms for long-term vasoconstriction can be identified and quantified in the spectrum of patients with essential hypertension, although the causes of this group of disorders are still obscure. The first vasoconstrictor mechanism is renin-angiotensin mediated and involves an increase in vascular smooth muscle cytosolic free calcium mobilized from intracellular sites. The degree of activity of this mechanism can be assessed by plasma renin level and/or by the hypotensive response to circulating anti-renin-system drugs (such as CEI inhibitors and beta blockers). The second vasoconstrictor mechanism, on the other hand, is renin-independent. It appears to require antecedent renal sodium retention and to be related to abnormal membrane influx of calcium. A low plasma renin level identifies this kind of vasoconstriction, which is also characterized by a low serum ionized calcium. Low-renin vasoconstriction is correctable by sodium depletion or by calcium channel or alpha adrenergic blockade. Depending on the state of sodium balance, these two vasoconstrictor mechanisms contribute reciprocally to maintenance of arteriolar tone in models of experimental hypertension, normotensive and hypertensive people, and in the vasoconstriction of edematous states, such as congestive heart failure. One of the two mechanisms also sustains diastolic hypertension in the experimental and clinical forms of renovascular hypertension and primary aldosteronism. Thus, both experimentally and clinically, at the polar extremes of the range of plasma renin values, one of the two mechanisms predominates: it is possible that, in the medium range of renin values, both mechanisms contribute to vasoconstriction. In our proposed unifying, analytic model, arteriolar vasoconstriction is associated with increased intracellular calcium and decreased magnesium levels in vascular smooth muscle. In the vasoconstriction consequent to sodium-volume expansion, cytosolic calcium is increased by an increased membrane influx. In renin-mediated vasoconstriction, receptor-operated channels mobilize cytosolic calcium instead from intracellular stores. These interrelationships provide a basis for stratifying hypertensive patients pathophysiologically and for applying simpler, more specific, and more rational therapies. Thus, the array of modern pharmacologic agents can often be rationally directed at one or the other, or both, of these two vasoconstrictor mechanisms.


A pilot study: Screening target miRNAs in tissue of nonsyndromic cleft lip with or without cleft palate.
Nonsyndromic cleft lip with or without cleft palate (NSCLP) has been recognized as a condition resulting from a combination of environmental and genetic factors. Studies have demonstrated that microRNAs (miRNAs) are involved in embryonic development. However, few studies have focused on screening potential target miRNAs in human NSCLP tissue. Using microarray-based miRNA expression profiling, miRNA expression was compared in tissue samples from 4 NSCLP patients and 4 healthy control subjects. Two hundred and fifty-four miRNAs were found to be differentially expressed. Changes in Homo sapiens (hsa)-miR-24-3p, hsa-miR-27b-3p, hsa-miR-205-5p, hsa-miR-1260b and hsa-miR-720 were of particular interest with respect to Wnt signaling (fold-changes were 12.5, 12.2, 12.1, 12.3 and 10.5, respectively; P<0.005 for all). The levels of hsa-miR-24-3p, hsa-miR-1260b and hsa-miR-205-5p were higher in tissues from NSCLP patients than in those from controls according to PCR analysis. Hsa-miR-24-3p, hsa-miR-1260b and hsa-miR-205-5p may be candidate miRNAs involved in the etiology of NSCLP via Wnt signaling.


They don't all look alike: individuated impressions of other racial groups.
Reliability, content, and homogeneity of own- and other-race impressions were assessed: U.S. White, U.S. Black, and Korean students rated faces of White, Black, or Korean men. High intraracial reliabilities revealed that people of 1 race showed equally high agreement regarding the traits of own- and other-race faces. Racially universal appearance stereotypes--the attractiveness halo effect and the babyface overgeneralization effect--contributed substantially to interracial agreement, which was only marginally lower than intraracial agreement. Moreover, similar attention to variations in appearance yielded similar degrees of own- and other-race trait differentiation. When own- and other-race differences in the differentiation of faces on babyfaceness were statistically controlled, differences in trait differentiation were eliminated. Despite the individuated impressions of other-race faces, certain racial stereotypes persisted.


Myasthenia gravis: Molecular mechanisms and promising therapeutic strategies.
Myasthenia gravis (MG) is a type of autoimmune disease caused by the blockage of neuromuscular junction transmission owing to the attack of autoantibodies on transmission-related proteins. Related antibodies, such as anti-AChR, anti-MuSK and anti-LRP4 antibodies, can be detected in most patients with MG. Although traditional therapies can control most symptoms, several challenges remain to be addressed, necessitating the development of more effective and safe treatment strategies for MG. With the in-depth exploration on the mechanism and immune targets of MG, effective therapies, especially therapies using biologicals, have been reported recently. Given the important roles of immune cells, cytokines and intercellular interactions in the pathological process of MG, B-cell targeted therapy, T-cell targeted therapy, proteasome inhibitors targeting plasma cell, complement inhibitors, FcRn inhibitors have been developed for the treatment of MG. Although these novel therapies exert good therapeutic effects, they may weaken the immunity and increase the risk of infection in MG patients. This review elaborates on the pathogenesis of MG and discusses the advantages and disadvantages of the strategies of traditional treatment and biologicals. In addition, this review emphasises that combined therapy may have better therapeutic effects and reducing the risk of side effects of treatments, which has great prospects for the treatment of MG. With the deepening of research on immunotherapy targets in MG, novel opportunities and challenges in the treatment of MG will be introduced.


Memory decline in older individuals predicts an objective indicator of oral health: findings from the Sydney Memory and Ageing Study.
Growing evidence suggests that there is an association between poor oral health and cognitive function in late adulthood. However, most studies to date have relied on cross-sectional research methods that do not permit inferences about the temporality of any association. Moreover, the few longitudinal studies that do exist have typically relied on small samples and quite limited cognitive or oral health assessments. The aim of the present study was therefore designed to provide the first direct evaluation of whether cognitive function is predictive of poor oral health in older adults. This longitudinal research included data from 339 participants aged 70 years or older from The Sydney Memory and Ageing Study (MAS), a large cohort of healthy community-dwelling older adults. Cognitive function was assessed using a battery of tests at baseline (Wave 1) in 2005 and six years later (Wave 4) in 2011. In 2015 (Wave 6), participants were assessed for oral health using the Oral Health Assessment Tool (OHAT), number of functional occluding pairs of natural teeth and sublingual resting saliva pH (SRSpH). Ordinal least squares regression analysis was used to model the effect of cognitive function on total OHAT score, and binomial logistic regression used for SRSpH and occluding pairs of functional teeth. Two models were tested. In the partially adjusted model, age, gender and years of education were included. The fully adjusted model additionally included medical conditions, general health, depression, smoking, alcohol consumption, functionality, and dental care utilization. The key finding to emerge was that a six-year change in memory (from Wave 1 to Wave 4) was associated with lower sublingual resting saliva pH at Wave 6 in partially (Odds Ratio (OR) = 0.65) and fully adjusted model (OR = 0.63). This longitudinal study provides further evidence that a relationship between cognitive function and oral health exists, and also points to this relationship potentially being bi-directional, as previous evidence suggests. The findings from the study also suggest that older adults who present with greater than normal memory decline at an earlier point in life were more likely to experience poor oral health when this was evaluated at a later time-point, four years later.


The association among smoking, HSV-1 exposure, and cognitive functioning in schizophrenia, bipolar disorder, and non-psychiatric controls.
Previous investigations have found that smokers with schizophrenia demonstrate reduced performance on cognitive tasks compared to non-smokers. However previous studies have not taken into account other environmental factors associated with cognitive functioning such as exposure to Herpes Simplex Virus type 1 (HSV-1). We examined these factors in a sample consisting of individuals with schizophrenia (n=773), bipolar disorder (n=493), or controls without a psychiatric disorders (n=548). Participants were assessed on a cognitive battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and had a blood sample drawn to measure seropositivity to HSV-1. Within each group linear regression models were constructed to determine whether cigarette smoking and HSV-1 seropositivity were jointly associated with cognitive functioning after adjusting for relevant covariates. Within the schizophrenia group, the effect size of lower total cognitive score was -0.279 (p<0.0001) for individuals who were both smokers and HSV-1 seropositive and a significant effect was found in all cognitive domains. The odds of being in the highest quartile of RBANS Total score were significantly lower for smokers (OR=0.58, 95% CI 0.41, 0.82, p=0.002). Smoking was not as consistently associated with levels of cognitive functioning in the bipolar disorder or the non-psychiatric control group. While experimental studies show that nicotine transiently improves functioning on sensory gating and attention tasks known to be deficient in schizophrenia, long-term nicotine exposure via smoking appears to have an adverse effect on cognitive functioning.


Cerebellar alterations in the weaver mouse.
The fine structure of the cerebellum of weaver mouse was examined and the paucity of granule cells and their axons, the parallel fibers, was confirmed. Unexpectedly, however, the dendritic spines of the Purkinje cells which, in normal animals, are the postsynaptic mates of the parallel fibers, were present. Furthermore, their essential morphology and their staining reactions were indistinguishable from those of the Purkinje cell dendritic spines in normal animals. Possible mechanisms of development are discussed.


Post-translational modifications in the nuclear region of young, aged, and cataract human lenses.
The urea-soluble proteins from the nucleus of two young, two aged, and two early-stage nuclear cataract lenses were subjected to tryptic digestion and analysis by 2D LC-MS/MS. Several novel post-translational modifications were identified. Deamidation was, by far, the most common modification. A number of differences were found in cataract compared to normal lenses, most notably an increase in the number of oxidized tryptophan residues. Semiquantitative analysis revealed that there appeared to be a trend toward increased levels of deamidation with age; however, there was no apparent increase upon the onset of nuclear cataract. This is in contrast to Trp oxidation, where an increase in the extent of modification was apparent in cataract lenses when compared to aged normal lenses. These findings suggest Trp oxidation may be involved in nuclear cataract development.


Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of five cases.
Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas. We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely re-excised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred. These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.


A case of anaplastic large cell lymphoma of skeletal muscle.
Anaplastic large cell lymphoma (ALCL) is a high grade non-Hodgkin lymphoma (NHL) that is comprised of the malignant proliferation of large lymphoid cells, which express CD30. Primary ALCL of the skeletal muscle is extremely uncommon. A 51-year-old Japanese female presented at our hospital with a 2-month history of severe pain and swelling of the right leg. A gallium-67 SPECT/CT scan showed a large mass involving the skeletal muscles from the gluteus to femoris. A biopsy of the mass demonstrated diffuse infiltration of medium and large neoplastic cells with round or lobulated hyperchromatic pleomorphic nuclei. A subset of Reed-Sternberg-like cells was also identified. Immunohistochemically, the neoplastic cells were strongly positive for CD4 and CD30, but negative for CD3, CD8, anaplastic lymphoma kinase (ALK), CD20, CD79α, CD21 and CD23. Based on the histological examination, this patient was diagnosed to have ALK-negative ALCL of the skeletal muscle. Further studies are needed to clarify the biological behavior of primary skeletal muscle ALCL.


Vaccination against nicotine does not prevent nicotine-induced changes in fetal nicotinic receptor binding and c-fos mRNA expression in rats.
Gestational exposure of rats to nicotine produces long-lasting alterations in brain development. Vaccination of adult female rats against nicotine reduces the distribution of maternally administered nicotine to fetal brain, suggesting that vaccination might protect against these effects. In the current study, the effects of vaccination on nicotine-induced changes in fetal (3)H-epibatidine binding and c-fos mRNA expression were evaluated using tissue from a previous pharmacokinetic study of vaccination. An intermittent nicotine dosing regimen designed to resemble nicotine intake in a smoker was administered from GD1-20. Peak nicotine levels in fetal brain were reduced by vaccination, whereas the chronic accumulation of nicotine in fetal brain was not. Gestational nicotine exposure produced significant increases in (125)I-epibatidine binding to brain and spinal cord on GD20, and decreased c-fos mRNA expression in fetal striatum, adrenal and lung. Vaccination did not significantly alter these effects. These data suggest that nicotine dosing, using a clinically relevant intermittent bolus dose regimen, produces substantial changes in fetal nicotinic receptor and c-fos mRNA expression. The decrease in c-fos mRNA expression contrasts with previously reported increases, and suggests that the nicotine dosing regimen used may influence its effects. The lack of effect of vaccination suggests that the cumulative exposure of fetal tissues to nicotine may influence the measured parameters to a greater extent than peak exposure levels.


Musculoskeletal pain, depression, and stress among Latino manual laborers in North Carolina.
The jobs of Latino manual laborers place their mental and physical health at risk. This study evaluates the associations among musculoskeletal pain, mental health, and work organization in Latino manual laborers. Farmworkers and nonfarmworkers (n = 189) in North Carolina were interviewed for self-reported musculoskeletal pain, depressive symptoms, stress, work safety climate, and precarious job status. More nonfarmworkers than farmworkers had neck and shoulder pain, but they did not differ in other areas of musculoskeletal pain. Depressive symptoms had a significant association with neck and shoulder pain (p < .05). Precariousness had a significant association with back pain (p < .05). Farmworker participants had H-2A visas and were afforded some protection compared to nonfarmworker manual workers. Research is needed to improve policy that relieves pain and improves mental health for all Latino manual workers.


Conservative, minimally invasive and open surgical repair for management of acute ruptures of the Achilles tendon: a clinical and functional retrospective study.
At present, it is unclear which is the best management for Achilles tendon rupture. We assess the clinical, functional and imaging outcomes of active patients undergoing 3 different types of management for acute subcutaneous rupture of the Achilles tendon, including conservative cast immobilization, traditional open surgery and percutaneous repair. 26 active patients were managed for a rupture of the Achilles Tendon from January 2007 to March 2008. Anthropometric measurements, Functional assessment, Isometric strength, Ultrasonographic assessment, Patient satisfaction, Working life, Physical activity, Functional score and Complications were recorded retrospectively. All 23 (21 men, 2 women) patients were reviewed at a minimum follow-up of 24 months (average 25.7, range 24 to 32 months, SD: 6.3) from the index injury. Thermann scores and patient satisfaction were significantly higher following surgery than conservative management with no significance between open and minimally invasive operated patients. Sensitive disturbances occur in up to 12% of open repairs and 1.8% of patients managed nonsurgically. Clinical and functional outcomes following surgical repair, percutaneous and open, of the Achilles tendon are significantly improved than following conservative management. Level III.


The less-than-satisfactory rhinoplasty: comparison of patient and surgeon satisfaction.
An analysis of patient response to less-than-ideal results in rhinoplasty reveals a marked discrepancy between the way patients react and the way in which surgeons think they would react. We feel that, by showing less-than-ideal results to prospective patients, we may be able to develop a method to predict the degree of dissatisfaction that a patient might show to a result that was less than ideal.


Autologous bone marrow transplantation in the treatment of children and adolescents with advanced malignant tumors.
Nineteen patients with advanced malignant tumors, less than 20 years old were treated with intensive chemotherapy (vincristine 2 mg/m2 i.v. and adriamycin 60 mg/m2 i.v. on day - 7; cyclophosphamide 45 mg/kg i.v. on days -6 to -3), total body irradiation (TBI, 600 rads on day -1) and autologous bone marrow transplantation (ABMT, day 0). Prior to this procedure induction of complete or partial remission by conventional therapy was attempted. Ten patients had intra-abdominal non-Hodgkin's lymphoma (NHL); three, yolk sac tumor; three, Ewing's sarcoma; and three, neuroblastoma. The supportive care included reverse isolation, immunoglobulin 400 mg/kg i.v. q 2 weeks, cotrimoxazole per os, and cell support as needed. No correlation between the bone marrow dose and the time of hematological reconstitution could be established. Five of seven patients with intra-abdominal NHL stage III (transplanted in first remission) are surviving disease-free for 5+, 5+, 20+, 23+, and 35+ months after ABMT. None of three patients with intra-abdominal NHL stage IV is surviving (two of them were transplanted in second remission). One of three patients with yolk sac tumor is surviving disease-free for 27+ months. There are no survivors among the patients with Ewing's sarcoma and neuroblastoma. Only one of 19 patients was lost due to therapeutic complications, while 12 died due to tumor. Regarding treatment results for advanced intra-abdominal NHL, the procedure described here is comparable to the best conventional regimens. In vitro methods for tumor cell eradication in the collected bone marrow might further improve the results of ABMT.


Asymptomatic bacteriuria Escherichia coli are live biotherapeutics for UTI.
Urinary tract infections (UTI) account for approximately 8 million clinic visits annually with symptoms that include acute pelvic pain, dysuria, and irritative voiding. Empiric UTI management with antimicrobials is complicated by increasing antimicrobial resistance among uropathogens, but live biotherapeutics products (LBPs), such as asymptomatic bacteriuria (ASB) strains of E. coli, offer the potential to circumvent antimicrobial resistance. Here we evaluated ASB E. coli as LBPs, relative to ciprofloxacin, for efficacy against infection and visceral pain in a murine UTI model. Visceral pain was quantified as tactile allodynia of the pelvic region in response to mechanical stimulation with von Frey filaments. Whereas ciprofloxacin promoted clearance of uropathogenic E. coli (UPEC), it did not reduce pelvic tactile allodynia, a measure of visceral pain. In contrast, ASB E. coli administered intravesically or intravaginally provided comparable reduction of allodynia similar to intravesical lidocaine. Moreover, ASB E. coli were similarly effective against UTI allodynia induced by Proteus mirabilis, Enterococccus faecalis and Klebsiella pneumoniae. Therefore, ASB E. coli have anti-infective activity comparable to the current standard of care yet also provide superior analgesia. These studies suggest that ASB E. coli represent novel LBPs for UTI symptoms.


Diagnosis of cysticercosis in endemic regions. The Cysticercosis Working Group in Peru.
Taenia solium cysticercosis is a frequent cause of neurological disease in developing countries. Specific diagnosis of cysticercosis is difficult. We obtained serum and/or CSF samples from 204 consecutive patients admitted to a neurological ward in Lima, Peru, and looked for antibodies specific for T solium with the enzyme-linked immunoelectrotransfer blot (EITB) assay. 21 (12%) of 173 serum samples from these patients were EITB-positive. In contrast, only 2 (1.5%) of 135 patients attending a public endoscopy clinic and 1 (1%) of 88 patients attending a private endoscopy clinic were seropositive. 1 (1%) of 98 pregnant women living in a Lima shanty town was EITB-positive. 15 (58%) of 26 neurology patients diagnosed clinically as having cysticercosis were seronegative. Routine screening by EITB of all patients with neurological symptoms from areas of endemic cysticercosis would avoid misdiagnosis of this common and treatable disease.


Perioperative nursing care when sudden patient death occurs in the OR.
This article explores how nurses cope with sudden death in the OR. It reviews the literature on this topic and explores grief and bereavement models, as well as provides a discussion of clinical coping methods identified through nursing experience. An education model presents information about implementing nursing care for the patient and family members. Critical care nursing research has been used to develop the model with adaptation to the perioperative setting. The model discusses the value of support for perioperative nurses and peers experiencing sudden patient death.


A Speech Sound Disorder Screening System Database Structure.
This paper makes a brief review of several database structures of Computer-Based Speech Therapy (CBST) systems and solutions and describes the screening method, an experimental study conducted to validate the screening algorithm and a database structure for the Information Entropy-Based Sound Speech Disorder (SSD) Screening System aimed at by our research project. The final part briefly presents the essential design criteria and further development.


Manipulation of a Senescence-Associated Gene Improves Fleshy Fruit Yield.
Senescence is the process that marks the end of a leaf's lifespan. As it progresses, the massive macromolecular catabolism dismantles the chloroplasts and, consequently, decreases the photosynthetic capacity of these organs. Thus, senescence manipulation is a strategy to improve plant yield by extending the leaf's photosynthetically active window of time. However, it remains to be addressed if this approach can improve fleshy fruit production and nutritional quality. One way to delay senescence initiation is by regulating key transcription factors (TFs) involved in triggering this process, such as the NAC TF ORESARA1 (ORE1). Here, three senescence-related NAC TFs from tomato (Solanum lycopersicum) were identified, namely SlORE1S02, SlORE1S03, and SlORE1S06. All three genes were shown to be responsive to senescence-inducing stimuli and posttranscriptionally regulated by the microRNA miR164 Moreover, the encoded proteins interacted physically with the chloroplast maintenance-related TF SlGLKs. This characterization led to the selection of a putative tomato ORE1 as target gene for RNA interference knockdown. Transgenic lines showed delayed senescence and enhanced carbon assimilation that, ultimately, increased the number of fruits and their total soluble solid content. Additionally, the fruit nutraceutical composition was enhanced. In conclusion, these data provide robust evidence that the manipulation of leaf senescence is an effective strategy for yield improvement in fleshy fruit-bearing species.


A Unique Dual-Readout High-Throughput Screening Assay To Identify Antifungal Compounds with Aspergillus fumigatus.
Treatment of invasive mold infections is limited by the lack of adequate drug options that are effective against these fatal infections. High-throughput screening of molds using traditional antifungal assays of growth is problematic and has greatly limited our ability to identify new mold-active agents. Here, we present a high-throughput screening platform for use with Aspergillus fumigatus, the most common causative agent of invasive mold infections, for the discovery of novel mold-active antifungals. This assay detects cell lysis through the release of the cytosolic enzyme adenylate kinase and, thus, is not dependent on changes in biomass or metabolism to detect antifungal activity. The ability to specifically detect cell lysis is a unique aspect of this assay that allows identification of molecules that disrupt fungal cell integrity, such as cell wall-active molecules. We also found that germinating A. fumigatus conidia release low levels of adenylate kinase and that a reduction in this background allowed us to identify molecules that inhibit conidial germination, expanding the potential for discovery of novel antifungal compounds. Here, we describe the validation of this assay and proof-of-concept pilot screens that identified a novel antifungal compound, PIK-75, that disrupts cell wall integrity. This screening assay provides a novel platform for high-throughput screens with A. fumigatus for the identification of anti-mold drugs. IMPORTANCE Fungal infections caused by molds have the highest mortality rates of human fungal infections. These devastating infections are hard to treat and available antifungal drugs are often not effective. Therefore, the identification of new antifungal drugs with mold activity is critical. Drug screening with molds is challenging and there are limited assays available to identify new antifungal compounds directly with these organisms. Here, we present an assay suitable for use for high-throughput screening with a common mold pathogen. This assay has exciting future potential for the identification of new drugs to treat these fatal infections.


Xenogenous fertilization of goat ova in the rabbit oviduct.
Eggs from superovulated goats were surgically placed in the oviducts of pseudopregnant rabbits previously inseminated with goat semen. Out of 81 eggs, 30 (37%) exhibited two pronuclei or two blastomeres when recovered 24-36 h later. Transplantation of these embryos into foster nanny goats resulted in the birth of kids.


Fatigue and fracture toughness of acrylic bone cements modified with long-chain amine activators.
The composition of acrylic bone cement has been identified as one of the important parameters affecting its mechanical properties and may, in turn, ultimately influence the longevity of a cemented arthroplasty. Our aim in this study was to determine the influence of change of one compositional variable, the activator, on the fatigue performance and fracture toughness of specimens of the fully cured cement. To that end, three sets of cements were prepared, containing either the conventional activator, 4-N,N dimethyl p-toluidine (DMPT), or novel ones that are tertiary amines based on long-chain fatty acids, that is, 4-N,N dimethylaminobenzyl oleate (DMAO) and 4-N,N dimethylaminobenzyl laurate (DMAL). In the fatigue tests, the specimens were subjected to tension-tension loading, and the results (number of cycles to failure, Nf) were analyzed using the linearized form of the three-parameter Weibull equation. The fracture toughness (KIc) tests were conducted with rectangular compact tension specimens. All fracture surfaces were subsequently examined with scanning electron microscopy. We found that the Weibull mean fatigue lives for specimens fabricated using the DMPT, DMAL, and DMAO containing cements were 272,823, 453,551, and 583,396 cycles, respectively. The corresponding values for KIc were 1.94 +/- 0.05, 2.06 +/- 0.09, and 2.00 +/- 0.07 MPa radical m, respectively. Statistical analyses showed that for both the DMAL- and DMAO-containing cements, the mean values of Nf were significantly higher compared to the corresponding value for the DMPT-containing cement (Mann-Whitney test; alpha < 0.10). This result is attributed to the higher molecular weights of the former cements compared to the latter. The same trend was found for the mean KIc values (Mann-Whitney test; alpha < 0.05), with the trend being explained in terms of the differences seen in the crack morphologies. These results thus demonstrate that these novel amines are viable alternatives to DMPT for incorporation into acrylic bone cement formulations in the future.


Benign retroperitoneal neural sheath tumors in patients without von Recklinghausen's disease.
Benign retroperitoneal neural sheath tumors in patients without von Recklinghausen's disease are quite rare and usually presented as isolated case reports. There are two types of benign neural sheath neoplasms: schwannoma and neurofibroma. Confusion exists in the nomenclature of these tumors due to the disagreement upon their cell of origin. In a collective report from two institutions, three cases with benign retroperitoneal neural sheath tumors are presented, and the histological features, diagnostic and therapeutic options are discussed.


Probing hydrogen-rich molecular systems at high pressures and temperatures.
Information on the behavior of hydrogen-containing simple molecular systems at high pressures and temperatures is central to many problems in chemistry and allied sciences. The combination of increasing pressure and temperature causes a redistribution of the electronic density, and the resulting alterations in interatomic interactions give rise to changes in macroscopic properties. Experimental studies of hydrogen-rich systems under extreme conditions have advanced considerably in recent years as a result of improvements in diamond anvil cell technology in combination with resistive- and laser-heating techniques. These experimental methods are combined with spectroscopic and diffraction techniques, and the results interpreted with the aid of molecular simulations. In this tutorial review we discuss recent findings in hydrogen, water, and other selected hydrogen-rich systems including compounds formed from these materials. The results are examined in terms of the evolution of effective potentials and interatomic vibrational coupling, molecular dissociation and recombination, ionization and polymerization, quantum effects, and order-disorder phenomena.


Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains.
Human maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) are small intestinal enzymes that work concurrently to hydrolyze the mixture of linear alpha-1,4- and branched alpha-1,6-oligosaccharide substrates that typically make up terminal starch digestion products. MGAM and SI are each composed of duplicated catalytic domains, N- and C-terminal, which display overlapping substrate specificities. The N-terminal catalytic domain of human MGAM (ntMGAM) has a preference for short linear alpha-1,4-oligosaccharides, whereas N-terminal SI (ntSI) has a broader specificity for both alpha-1,4- and alpha-1,6-oligosaccharides. Here we present the crystal structure of the human ntSI, in apo form to 3.2 A and in complex with the inhibitor kotalanol to 2.15 A resolution. Structural comparison with the previously solved structure of ntMGAM reveals key active site differences in ntSI, including a narrow hydrophobic +1 subsite, which may account for its additional substrate specificity for alpha-1,6 substrates.


[Effect of micro-implant assisted rapid palatal expansion in patients with different radiographic stages of mid-palatal suture maturation].
Objective: To evaluate the effect of micro-implant assisted rapid palatal expansion (MARPE) in patients with different radiographic stages of midpalatal suture maturation. Methods: Twenty-eight patients [7 males and 21 females; age (15.5±5.5) years] with maxillary transverse deficiency were selected in the Department of Orthodontics, Hospital of Stomatology, Jilin University from February 2017 to October 2019. According to the fusion of the midpalatal suture, the patients were divided into two groups: 10 patients [3 males and 7 females; age (19.9±6.9) years] were in fusion group and 18 patients [4 males and 14 females; age (13.0±2.4) years] were in non-fusion group. Each patient had cone-beam CT (CBCT) images taken immediately after the placement of micro-implants (T1) and the completion of maxillary expansion (T2). The CBCT images were analyzed using the Dolphin Imaging software to evaluate the amount of midpalatal expansion and the percentages of bony expansion, etc. Statistical analysis was carried out to compare the two groups. Results: After MARPE treatment, the amount of sutural expansion in fusion group was (3.23±1.45) mm while that in non-fusion group was (4.97±1.47) mm (P<0.05). There was a statistically significant difference in the percentages of bony expansion efficiency between the non-fusion group (71±20)% and the fusion group (46±18)% (P<0.05). Conclusions: Bony expansion efficiency was affacted by the radiographic stages of midpalatal suture maturation.


[Analysis of the chloroplast genome characteristics of Rhus chinensis by de novo sequencing].
Rhus chinensis is an important economic species, which could provide raw materials for pharmaceutical and industrial dyes. Rhus chinensis is famous for its resistance to drought, cold, and salt. It grows in temperate, warm temperate, and subtropical regions. We report here Rhus chinensis chloroplast genomes by de novo sequencing. The results show that the length of Rhus chinensis was 159 082 bp, exhibiting a typical four-part structure with two single-copy regions (long single copy [LSC] and short single copy [SSC] sections) separated by a pair of inverted repeats (IRs). The length of LSC and SSC was 85 394 bp and 18 663 bp, respectively. The genomes contained 126 genes, including 88 protein encoding genes, 8 rRNA and 30 tRNA genes. In the chloroplast genome, 61.97% of the sequence were gene coding region. In the sequence of gene encoding region, the vast majority of sequences were protein encoding region, accounting for 86.65%, followed by rRNA (10 620 bp, 10.77%) and tRNA (2 540 bp, 2.58%). In Rhus chinensis chloroplast genome, only 8 genes contain introns, all containing 1 intron except ycf3 gene (2 introns). The Rhus chinensis chloroplast genome contains 755 SSR locies. SSR mainly consists of dinucleotide and mononucleotide, accounting for 60% (453) and 28.74% (217) respectively. The clustering results show that Anacardiaceae were closest to Rhus chinensis, followed by Aceraceae and Sapindaceae. This study provides a molecular basis for the classification of Rhus chinensis.


Refeeding syndrome in small ruminants receiving parenteral nutrition.
Small ruminants presented to tertiary care facilities commonly suffer from severe protein-calorie malnutrition. Some of these patients require parenteral nutrition (PN; amino acids and dextrose with or without lipids) during hospitalization. Refeeding syndrome, a potentially fatal shift of electrolytes seen in malnourished patients during refeeding, may occur. (a) To report the prevalence of refeeding syndrome in small ruminants receiving PN and (b) to determine risk factors for the development of refeeding syndrome. Hospitalized small ruminants (n = 20) that received PN from 2010 to 2018 and that had serial (≥2) monitoring of serum electrolyte concentrations after initiation of PN. Retrospective case series. Refeeding syndrome was defined as the presence of at least 2 of the following electrolyte abnormalities after initiation of PN: hypophosphatemia, hypokalemia, hypomagnesemia, or some combination of these. Data was analyzed using Fisher's exact test, followed by univariate logistic regression. Eleven of 20 (55%) animals met the definition of refeeding syndrome. Mean minimum serum phosphorus concentration in animals with refeeding syndrome was 1.96 ± 0.69 mg/dL (reference range, 4.2-7.6 mg/dL). Eleven of 20 animals survived to discharge. Survival rate did not differ significantly between refeeding cases (4/11, 36.3%) and nonrefeeding cases (7/9, 77.8%; P = .09). Mean serum phosphorus concentration was significantly lower in nonsurvivors than in survivors (1.88 ± 0.10 mg/dL vs 4.32 ± 0.70 mg/dL, P = .006). We report the prevalence of refeeding syndrome in small ruminants receiving PN. Clinicians should anticipate refeeding syndrome after initiation of PN and consider pre-emptive supplementation with phosphorus, potassium, magnesium, or some combination of these.


An Optimizing Surgical Procedures for Correcting Severe Constricted Ears: Helix Costal Cartilage Scaffold Combined With V-Y Advanced Flap.
A constricted ear is a deformity that is distinguished by curling of the upper portion of the ear, which includes the helix, scapha, and antihelix. The treatment for severely constricted ears seems to be quite invasive. To reduce invasiveness and fully utilize the folded cartilage, the authors used a helix costal cartilage scaffold combined with a single V-Y advanced flap in the correction of Tanzer type IIB constricted ear deformity to investigate the clinical effect. From 2020 to 2021, autologous costal cartilage helix stent combined with local V-Y advanced flap was applied to correct the constricted ear malformation in 18 patients admitted to the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences. All patients were followed for a duration of 6 to 12 months (average 7 months). Reconstructed auricles were cosmetically satisfying, with a natural-looking helix and enlarged cavum conchae cavity, as well as auricle sizes that were close to normal and near symmetry between both ears. With satisfactory clinical results, our technique can be used to repair types IIB cup ear deformities. It has a broad range of practical applications.