Kissing Balloon Technique for Angioplasty of Tibioperoneal Arteries Bifurcation Using Pedal Arterial Retrograde Revascularization.
Kissing Balloon Technique using retrograde pedal approach together with anterograde common femoral artery (CFA) approach could be the treatment of choice in patients with diseased infrapopliteal artery bifurcation. We report seven cases where the KBT was utilized for the treatment of diseased infrapopliteal artery bifurcation using retrograde pedal access in conjunction with the conventional common femoral artery (CFA) access. We reviewed all seven cases that underwent KBT with the combination of pedal and common femoral access in a single-center study from 2014 to 2015 utilizing Rutherford classification severity index; all cases were deemed stage 3 (severe claudication) to stage 6 (severe ischemic ulcers or frank gangrene). With the exception of two cases, contralateral femoral access was obtained, with sheath sizes varying from 4 to 6 French for both CFA and pedal access. Ultrasound was utilized for ipsilateral pedal access in all seven cases. Arterial revascularization was successfully achieved by the KBT in all patients without any complications. All patients achieved procedural success, which is defined as residual stenosis of less than 30% with no dissection or thrombosis and clinical success that is defined as resolution of symptoms (absence of intermittent claudication and healing of the ulcer) as well as improvement in the arterial brachial index (ABI). During follow-up, out of the seven cases, repeat angiogram was performed for one case, which showed patent arteries with no residual lesions. In patients with popliteal and tibioperoneal trunk bifurcation lesions, Kissing Balloon Technique using retrograde pedal access in conjunction with the conventional anterograde access appeared to be successful, safe, and effective technique with lower access site complications and shorter procedure time.


Angiographic studies of Quinton-Scribner arteriovenous cannulae.
An analysis of 86 angiographic studies of Quinton-Scribner shunts has shown that these may be very useful in determining the cause and helping in the management of poorly functioning cannulae in patients on regular haemodialysis treatment.


NODDI reproducibility and variability with magnetic field strength: A comparison between 1.5 T and 3 T.
Diffusion models are advantageous for examining brain microstructure non-invasively and their validation is important for transference into the clinical domain. Neurite Orientation Dispersion and Density Imaging (NODDI) is a promising model for estimating multiple diffusion compartments from MRI data acquired in a clinically feasible time. As a relatively new model, it is necessary to examine NODDI under certain experimental conditions, such as change in magnetic field-strength, and assess it in relation to diffusion tensor imaging (DTI), an established model that is largely understood by the neuroimaging community. NODDI measures (intracellular volume fraction, νic , and orientation distribution, OD) were compared with DTI at 1.5 and 3 T data in healthy adults in whole-brain tissue masks and regions of white- and deep grey-matter. Within-session reproducibility and between-subject differences of NODDI with field-strength were also investigated. Field-strength had a significant effect on NODDI measures, suggesting careful interpretation of results from data acquired at 1.5 and 3 T. It was demonstrated that NODDI is feasible at 1.5 T, but with lower νic in white-matter regions compared with 3 T. Furthermore, the advantages of NODDI over DTI in a region of complex microstructure were shown. Specifically, in the centrum-semiovale where FA is typically as low as in grey-matter, νic was comparable to other white-matter regions yet accompanied by an OD similar to deep grey-matter. In terms of reproducibility, NODDI measures varied more than DTI. It may be that NODDI is more susceptible to noisier parameter estimates when compared with DTI, conversely it may have greater sensitivity to true within- and between-subject heterogeneity. Hum Brain Mapp 37:4550-4565, 2016. © 2016 Wiley Periodicals, Inc.


Answers from the audit trail.
It's a lot cheaper to develop a compliance plan than fight fraud charges. Trouble is, off-the-shelf wisdom is hard to come by. Here's sage advice from compliance pros on how to put your plan in motion.


Impact of Lipid and Protein Co-oxidation on Digestibility of Dairy Proteins in Oil-in-Water (O/W) Emulsions.
Enrichment of polyunsaturated fatty acids (PUFAs) is a growing trend in the food industry. However, PUFAs are known to be susceptible to lipid oxidation. It has been shown that oxidizing lipids react with proteins present in the food and that as a result polymeric protein complexes are produced. Therefore, the aim of this work was to investigate the impact of lipid and protein co-oxidation on protein digestibility. Casein and whey protein (6 mg/mL) based emulsions with 1% oil with different levels of PUFAs were subjected to respectively autoxidation and photo-oxidation. Upon autoxidation at 70 °C, protein digestibility of whey protein based emulsions containing fish oil decreased to 47.7 ± 0.8% after 48 h, whereas in the controls without oil 67.8 ± 0.7% was observed. Upon photo-oxidation at 4 °C during 30 days, mainly casein-based emulsions containing fish oil were affected: the digestibility amounted to 43.9 ± 1.2%, whereas in the control casein solutions without oil, 72.6 ± 0.2% of the proteins were digestible. Emulsions containing oils with high PUFA levels were more prone to lipid oxidation and thus upon progressive oxidation showed a higher impact on protein digestibility.


Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study.
The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m2/cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m2/cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.


Outcome after acute Achilles tendon rupture is not negatively affected by female sex and age over 65 years.
Studies suggest that women have worse treatment outcome than men after acute Achilles tendon rupture (ATR). The aim of this study was to investigate if sex and age affect treatment outcome after ATR. The study was performed as a registry study in the Danish Achilles tendon Database. The primary outcome was change in the Achilles tendon Total Rupture Score (ATRS) from baseline to 4 months, 1 year and 2 years follow-up. Variables of interest were sex and age group (< 40 years, 40-65 years and > 65 years). Data were collected from April 2012 to March 2018. Five-hundred and sixteen patients (416 men, 100 women) were included in the study population. At baseline, women scored 4.3 points lower in ATRS compared to men. No statistically significant difference between the sexes regarding change in ATRS were found. Women scored statistically significantly less in absolute ATRS at 1 year follow-up (mean difference 9.4; 95% CI 3.8, 14.9; P = 0.03). Patients older than 65 years scored statistically significantly more in ATRS change compared to patients between 40-65 years (mean difference 12.8; 95% CI 6.1-19.5; P < 0.001). This study did not show a statistically significant or clinically relevant difference between the sexes in ATRS change from baseline to follow-up. The mean difference in ATRS change between patients older than 65 years and patients between 40-65 years was clinically relevant with better outcome for patients older than 65 years. When comparing ATRS between groups with an unequal sex distribution, the findings of a baseline difference and a difference in absolute ATRS at 1 year follow-up between the sexes, advocate for reporting of sex-specific data or for use of change in ATRS from baseline to follow-up instead of absolute ATRS. Level III.


Antitumor activity of 7-O-succinyl macrolactin A tromethamine salt in the mouse glioma model.
Chemoradiotherapy with temozolomide is the current standard treatment option for patients with glioblastoma. However, the majority of patients with glioblastoma survive for <2 years. Therefore, it is necessary to develop more effective therapeutic strategies for the treatment of glioblastoma. 7-O-succinyl macrolactin A tromethamine salt (SMA salt), a macrolactin compound, is known to possess an antiangiogenic activity. The present study investigated the antitumor effects of SMA salt in the treatment of glioblastoma by evaluating in vitro and in vivo antitumor effects of SMA salt in an experimental glioblastoma model. The antitumor effects of the drug on human glioblastoma U87MG, U251MG and LN229 cell lines were assessed using in vitro cell viability, migration and invasion assays. Nude mice with established U87MG glioblastoma were assigned to either the control or SMA salt treatment group. The volume of tumors and the duration of survival were also measured. SMA salt affected cell viability and caused a concentration-dependent inhibition effect on the migration and invasion of glioblastoma cell lines. Animals in the SMA salt treatment group demonstrated a significant reduction in tumor volume and an increase in survival (P<0.05). Treatment with SMA salt presented more cytotoxic effects as well as anti-migration and anti-invasion activity compared with the control group in vitro and in vivo. These results suggest that SMA salt has significant antitumor effects on glioblastoma.


Diverse functional roles of monosaccharide transporters and their homologs in vascular plants: a physiological perspective.
Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter(-like) gene superfamily is large and functionally diverse, while the recently identified SWEET transporter family is smaller and, thus far, only found to transport glucose. These transporters play essential roles at many levels, ranging from organelles to the whole plant. Many family members are essential for cellular homeostasis and reproductive success. Although most transporters do not directly participate in long-distance transport, their indirect roles greatly impact carbon allocation and transport flux to the heterotrophic tissues of the plant. Functional characterization of some members from both gene families has revealed their diverse roles in carbohydrate partitioning, phloem function, resource allocation, plant defense, and sugar signaling. This review highlights the broad impacts and implications of monosaccharide transport by describing some of the functional roles of the monosaccharide transporter(-like) superfamily and the SWEET transporter family.


Clinical features of malignant transformation in benign laryngeal papillomata.
Laryngeal papillomata can undergo spontaneous malignant transformation without being detected histologically and, in some instances, the disease may become so advanced, before the diagnosis is confirmed, that it is beyond any form of curative treatment. Because of this limitation imposed by histopathological investigation, a study was undertaken in 17 adults with benign laryngeal papillomata, (three of whom underwent malignant transformation) to determine whether malignant transformation can be predicted from the clinical behaviour of the tumour. The following features were analysed: age, sex, patient's symptoms, frequency of excision of the papillomata, site of lesion, presence or absence of laryngeal oedema, the need for tracheostomy, vocal fold mobility and presence or absence of cervical lymph nodes. It was found that decreased vocal fold mobility, the presence of cervical lymph nodes, exuberant and rapid growth requiring very frequent excisions, oedema of the larynx with airway obstruction requiring a tracheostomy are clinical features suggestive of malignant transformation.


[Chemically methylated DNA repair in Escherichia coli--the role of alkB protein].
Methylating agents belong to mutagens occurring most frequently in our environment. They methylate mainly the nitrogen bases in DNA and RNA, affecting their functions. In E. coli the alkylated bases are repaired by proteins and enzymes either permanently present in the cells (Ogt, Ada) or produced transiently (Ada, AlkB, AlkA, Aid), after induction of the Ada defence system. Alkylating agents induce also the SOS system, which enhances the synthesis of about 40 proteins, including those participating in recombination, replication and mutagenesis of DNA. All DNA interactions, modifications and repairs constitute an amazing and highly efficiently functioning cellular system. Among the repair proteins there are some which affect the alkylated bases in a non-conventional way, very rarely occurring in nature. Especially amazing is the mechanism of action of dioxogenase AlkB, which combines the repair of methyl-, ethyl- and etheno-base derivatives with oxidation and dissociation of the modified groups, leading to direct recovery of natural bases. This review attempts to elucidate the role of the individual proteins involved in the repair processes.


Effects of 6% Tetrastarch and Lactated Ringer's Solution on Extravascular Lung Water and Markers of Acute Renal Injury in Hemorrhaged, Isoflurane-Anesthetized Healthy Dogs.
Tetrastarch can cause acute kidney injury (AKI) in humans with sepsis, but less likely to result in tissue edema than lactated Ringer's solution (LRS). Compare effects of volume replacement (VR) with LRS and 6% tetrastarch solution (TS) on extravascular lung water (EVLW) and markers of AKI in hemorrhaged dogs. Six healthy English Pointer dogs (19.7-35.3 kg). Prospective crossover study. Animals underwent anesthesia without hemorrhage (Control). Two weeks later, dogs hemorrhaged under anesthesia on 2 occasions (8-week washout intervals) and randomly received VR with LRS or TS at 3 : 1 or 1 : 1 of shed blood, respectively. Anesthesia was maintained until 4 hour after VR for EVLW measurements derived from transpulmonary thermodilution cardiac output. Neutrophil gelatinase-associated lipocalin (NGAL) and creatinine concentrations in plasma and urine were measured until 72 hour after VR. The EVLW index (mL/kg) was lower at 1 hour after TS (10.0 ± 1.9) in comparison with controls (11.9 ± 3.4, P = 0.04), and at 4 hour after TS (9.7 ± 1.9) in comparison with LRS (11.8 ± 2.7, P = 0.03). Arterial oxygen partial pressure-to-inspired oxygen fraction ratio did not differ among treatments from 0.5 to 4 hour after VR. Urine NGAL/creatinine ratio did not differ among treatments and remained below threshold for AKI (120,000 pg/mg). Although TS causes less EVLW accumulation than LRS, neither fluid produced evidence of lung edema (impaired oxygenation). Both fluids appear not to cause AKI when used for VR after hemorrhage in healthy nonseptic dogs.


Prostacyclin mimetics inhibit DRP1-mediated pro-proliferative mitochondrial fragmentation in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a rare cardiopulmonary disorder, involving the remodelling of the small pulmonary arteries. Underlying this remodelling is the hyper-proliferation of pulmonary arterial smooth muscle cells within the medial layers of these arteries and their encroachment on the lumen. Previous studies have demonstrated an association between excessive mitochondrial fragmentation, a consequence of increased expression and post-translational activation of the mitochondrial fission protein dynamin-related protein 1 (DRP1), and pathological proliferation in PASMCs derived from PAH patients. However, the impact of prostacyclin mimetics, widely used in the treatment of PAH, on this pathological mitochondrial fragmentation remains unexplored. We hypothesise that these agents, which are known to attenuate the proliferative phenotype of PAH PASMCs, do so in part by inhibiting mitochondrial fragmentation. In this study, we confirmed the previously reported increase in DRP1-mediated mitochondrial hyper-fragmentation in PAH PASMCs. We then showed that the prostacyclin mimetic treprostinil signals via either the Gs-coupled IP or EP2 receptor to inhibit mitochondrial fragmentation and the associated hyper-proliferation in a manner analogous to the DRP1 inhibitor Mdivi-1. We also showed that treprostinil recruits either the IP or EP2 receptor to activate PKA and induce the phosphorylation of DRP1 at the inhibitory residue S637 and inhibit that at the stimulatory residue S616, both of which are suggestive of reduced DRP1 fission activity. Like treprostinil, MRE-269, an IP receptor agonist, and butaprost, an EP2 receptor agonist, attenuated DRP1-mediated mitochondrial fragmentation through PKA. We conclude that prostacyclin mimetics produce their anti-proliferative effects on PAH PASMCs in part by inhibiting DRP1-mediated mitochondrial fragmentation.


Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) in blood samples of occupationally exposed workers from a transformer recycling plant in Dortmund, Germany-initial findings.
Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) were determined in 23 blood samples of exposed workers from a transformer recycling plant in Dortmund, Germany. Compared to the most recent studies on German background levels of adults, elevated concentrations of up to 71.6 pg WHO(2005)-TEq/g(lipid base) were found for 8 participants, and for individual PCDF congeners for 15 participants.


Working memory management and predicted utility.
Given the limited capacity of working memory (WM), its resources should be allocated strategically. One strategy is filtering, whereby access to WM is granted preferentially to items with the greatest utility. However, reallocation of WM resources might be required if the utility of maintained information subsequently declines. Here, we present behavioral, computational, and neuroimaging evidence that human participants track changes in the predicted utility of information in WM. First, participants demonstrated behavioral costs when the utility of items already maintained in WM declined and resources should be reallocated. An adapted Q-learning model indicated that these costs scaled with the historical utility of individual items. Finally, model-based neuroimaging demonstrated that frontal cortex tracked the utility of items to be maintained in WM, whereas ventral striatum tracked changes in the utility of items maintained in WM to the degree that these items are no longer useful. Our findings suggest that frontostriatal mechanisms track the utility of information in WM, and that these dynamics may predict delays in the removal of information from WM.


Cardiac biomarkers in haemodialysis patients: the prognostic value of amino-terminal pro-B-type natriuretic peptide and cardiac troponin T.
Cardiac biomarkers such as amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTNT) provide information on cardiovascular morbidity and mortality in patients with normal renal function. In a considerable number of chronic haemodialysis patients, both biomarkers - NT-proBNP and cTNT - are elevated despite the absence of cardiac ischaemia. The elevation of cardiac biomarkers in chronic haemodialysis patients is of prognostic value with respect to cardiovascular morbidity and mortality. They provide a useful rationale for the screening of occult cardiac disease and optimization of the dialysis procedure with respect to volume control.


Spirosoma rhododendri sp. nov., isolated from a flower of royal azalea (Rhododendron schlippenbachii).
A Gram-negative, non-motile, strictly aerobic and rod- or filamentous-shaped strain, CJU-R4T, was isolated from a flower of royal azalea (Rhododendron schlippenbachii) collected in the Republic of Korea. Strain CJU-R4T was catalase-positive and oxidase-negative, and grew at 15-33 °C (optimum, 28-20 °C), at pH 5.0-8.0 (optimum, pH 7.0-8.0), and in the presence of 0-1 % NaCl (w/v; optimum, 0 %). Strain CJU-R4T had the highest 16S rRNA gene sequence similarity to Spirosoma oryzae RHs22T (96.6 %), revealing less than 93 % sequence similarity to other type strains. Phylogenetic and phylogenomic analysis also revealed strain CJU-R4T formed a robust cluster with S. oryzae RHs22T. The major fatty acids were summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c; 33.0 %), C16 : 1 ω5c (22.1 %), iso-C15 : 0 (12.6 %) and C16 : 0 (10.7 %). The polar lipids were composed of phosphatidylethanolamine, three unidentified aminophospholipids, one unidentified phospholipid and four unidentified lipids. Menaquinone-7 was detected as the sole respiratory quinone. The genomic DNA G+C content was 55.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain CJU-R4T and Spirosoma oryzae DSM 28354T were 81.5 and 23.9 %, respectively. Based on the results of the phenotypic and genotypic analyses, strain CJU-R4T is considered to represent a novel species of the genus Spirosoma, for which the name Spirosoma rhododendri sp. nov. is proposed. The type strain is CJU-R4T (=KACC 21264T=NBRC 114513T).


Role of dopaminergic receptors in glaucomatous disease modulation.
Both studies on animals and humans suggest the presence of dopamine (DA) receptors in the anterior segment of the eye. Their role in the dynamics of intraocular pressure (IOP) is not yet clear. DA2 and DA3 receptors are mainly located on postganglionic sympathetic nerve endings. Their stimulation reduces the release of norepinephrine and suppresses the production of aqueous humor. DA1 receptors seem to be more expressed by the ciliary body and the outflow pathway of aqueous humor. The administration of DA1-selective agonists stimulates the production of aqueous humor, increasing IOP, whereas DA2- and DA3-selective agonists could reduce IOP and, therefore, the risk to develop a glaucoma (GL). GL is a broad spectrum of eye diseases which have in common the damage to the optic nerve and the progressive loss of the visual field. Further studies are desirable to clarify the role of the dopaminergic system and the usefulness of DA2 and DA3 agonists in reducing IOP.


R229Q Polymorphism of NPHS2 Gene in Group of Iraqi Children with Steroid-Resistant Nephrotic Syndrome.
Background. The polymorphism R229Q is one of the most commonly reported podocin sequence variations among steroid-resistant nephrotic syndromes (SRNS). Aim of the Study. We investigated the frequency and risk of this polymorphism among a group of Iraqi children with SRNS and steroid-sensitive nephrotic syndrome (SSNS). Patients and Methods. A prospective case control study which was conducted in Al-Imamein Al-Kadhimein Medical City, spanning the period from the 1st of April 2015 to 30th of November 2015. Study sample consisted of 54 children having NS, divided into 2 groups: patients group consisted of 27 children with SRNS, and control group involved 27 children with SSNS. Both were screened by real time polymerase chain reaction for R229Q in exon 5 of NPHS2 gene. Results. Molecular study showed R229Q polymorphism in 96.3% of SRNS and 100% of SSNS. There were no phenotypic or histologic characteristics of patients bearing homozygous R229Q polymorphism and the patients with heterozygous R229Q polymorphism. Conclusion. Polymorphism R229Q of NPHS2 gene is prevalent in Iraqi children with SRNS and SSNS. Further study needs to be done, for other exons and polymorphism of NPHS2 gene in those patients.


DNA released from rejecting organs is an indicator of the degree of graft cellular damage.
Warm and cold ischemia as well as rejection of the transplanted organ or tissue cause destructive changes in the graft parenchyma. Fragments of disintegrated cellular organelles are phagocytized and digested by recipient scavenger cells in lymph nodes, spleen, and liver. Some fragments engulfed by dendritic cells are processed including donor DNA present in the ingested cellular debris. The question arises as to whether the DNA from the disintegrated cells may be used as a measure of graft damage. In this study we provide evidence that both syngeneic and allogeneic organ transplantation followed by "seeding" of donor DNA from graft cells is internalized in recipient macrophages and dendritic cells in lymphoid organs. The kinetics of accumulation of donor DNA in recipient tissues reflected the degree of ischemic and immune graft damage. Immunosuppression with cyclosporine or tacrolimus did not significantly attenuate the DNA release. Measurements of the concentration of donor DNA gives insight into the kinetics of allograft rejection. Real-time polymerase chain reaction for donor DNA in recipient serum and blood leukocytes that have engulfed donor cell debris may be useful for clinical diagnostic application.


Health Care Professional Perceptions About a Proposed NICU Intervention: The Importance of Community and Aligning With Everyday Occupations.
The neonatal intensive care unit (NICU) is a dynamic system with multiple stakeholders and contextual factors impacting the implementation of novel practices. This qualitative study aimed to (a) define health care professionals' perceptions on the feasibility of implementing a sensory intervention to study its efficacy, and (b) elaborate on transactions occurring between NICU health care professionals and the proposed research. Eleven NICU professionals participated in one of three focus groups that were audio-recorded, transcribed, and analyzed thematically in NVivo first descriptively and then interpretively through a transactionalism lens. The health care professionals implied the intervention was feasible, but provided multiple suggestions to enhance implementation. The modification of familiar occupational practices, ingrained habits, and the potential impact on the collective occupational performance of NICU community members arose. Understanding occupations within the NICU as transactional allows for a broader view of occupational engagement and enhances knowledge of the nuances related to implementing clinical changes.


Sperm antibodies and human fertilization.
Previous investigations using zona-free hamster oocytes and salt-stored human zonae pellucidae, and retrospective analysis of routine human in vitro fertilization (IVF) results have suggested that sperm antibodies can impair the fertilizing capacity of human spermatozoa. The results of our investigations using viable human oocytes confirm that human antispermatozoal antibodies can inhibit fertilization by human spermatozoa. In the future we plan to examine the mechanism of fertilization inhibition, including characterization of the sperm antigens involved. These studies may facilitate the development of immunocontraceptive vaccines and of new treatments for immunological infertility.


Malaria and helminth interactions in humans: an epidemiological viewpoint.
In the tropics, helminths are among the most common chronic infections of humans and Plasmodium infections the most deadly. As these two groups of parasites have similar geographical distributions, co-infection is commonplace. It has increasingly been speculated that helminth infections may alter susceptibility to clinical malaria, and there is now increasing interest in investigating the consequences of co-infection, with studies yielding contrasting results. The immunological interactions between helminths and malarial parasites are unclear, although several hypotheses have been proposed. This review provides an epidemiological overview of the possible interactions between helminths and malarial parasites, in relation to geographical distributions and disease patterns, and provides a critical discussion of the results of the epidemiological studies that have so far been conducted to investigate the possible associations. Future studies that might be considered, in order to address the gaps in knowledge, are also considered.


Artemisinin and AIEgen Conjugate for Mitochondria-Targeted and Image-Guided Chemo- and Photodynamic Cancer Cell Ablation.
Cell organelle targeting is a promising approach for cancer therapy. We herein report a light-up probe (tetraphenylethenethiophene (TPETH)-Mito-1ART) to co-deliver artemisinin (ART) and an aggregation-induced emission (AIE) photosensitizer to cancer cell mitochondria for image-guided combination cancer cell ablation. This probe contains a TPETH core, two mitochondria targeting arms with ART on one arm, which show high specificity toward cancer cells over normal ones, predominant accumulation, and fluorescence turn-on in mitochondria. The fresh heme produced in mitochondria quickly activates ART, and the direct generation of reactive oxygen species at mitochondria promotes photodynamic therapy (PDT) performance. The incorporation of ART and PDT leads to a largely improved cancer cell ablation efficacy with a synergistic effect, which could quickly depolarize mitochondrial membrane and largely reduce cancer migration activity. This co-delivery strategy provides great potentials for subcellular organelle-targeted and image-guided combination cancer cell ablation.


Crystal Structures and Nuclear Magnetic Resonance Studies of the Apo Form of the c-MYC:MAX bHLHZip Complex Reveal a Helical Basic Region in the Absence of DNA.
The c-MYC transcription factor is a master regulator of cell growth and proliferation and is an established target for cancer therapy. This basic helix-loop-helix Zip protein forms a heterodimer with its obligatory partner MAX, which binds to DNA via the basic region. Considerable research efforts are focused on targeting the heterodimerization interface and the interaction of the complex with DNA. The only available crystal structure is that of a c-MYC:MAX complex artificially tethered by an engineered disulfide linker and prebound to DNA. We have carried out a detailed structural analysis of the apo form of the c-MYC:MAX complex, with no artificial linker, both in solution using nuclear magnetic resonance (NMR) spectroscopy and by X-ray crystallography. We have obtained crystal structures in three different crystal forms, with resolutions between 1.35 and 2.2 Å, that show extensive helical structure in the basic region. Determination of the α-helical propensity using NMR chemical shift analysis shows that the basic region of c-MYC and, to a lesser extent, that of MAX populate helical conformations. We have also assigned the NMR spectra of the c-MYC basic helix-loop-helix Zip motif in the absence of MAX and showed that the basic region has an intrinsic helical propensity even in the absence of its dimerization partner. The presence of helical structure in the basic regions in the absence of DNA suggests that the molecular recognition occurs via a conformational selection rather than an induced fit. Our work provides both insight into the mechanism of DNA binding and structural information to aid in the development of MYC inhibitors.


Near-field sound radiation of fan tones from an installed turbofan aero-engine.
The development of a distributed source model to predict fan tone noise levels of an installed turbofan aero-engine is reported. The key objective is to examine a canonical problem: how to predict the pressure field due to a distributed source located near an infinite, rigid cylinder. This canonical problem is a simple representation of an installed turbofan, where the distributed source is based on the pressure pattern generated by a spinning duct mode, and the rigid cylinder represents an aircraft fuselage. The radiation of fan tones can be modelled in terms of spinning modes. In this analysis, based on duct modes, theoretical expressions for the near-field acoustic pressures on the cylinder, or at the same locations without the cylinder, have been formulated. Simulations of the near-field acoustic pressures are compared against measurements obtained from a fan rig test. Also, the installation effect is quantified by calculating the difference in the sound pressure levels with and without the adjacent cylindrical fuselage. Results are shown for the blade passing frequency fan tone radiated at a supersonic fan operating condition.


High effective time-dependent THz spectroscopy method for the detection and identification of substances with inhomogeneous surface.
We discuss an effective time-dependent THz spectroscopy method for the detection and identification of a substance with an inhomogeneous surface using a broadband THz signal reflected from the substance. We show that a successful and reliable identification can be made using the single long-duration THz signal, which contains not only the main reflected pulse, but also several sub-pulses. The method does not use averaging of the measured THz signals over the viewing angles and scanning over the surface area, which significantly increases the signal processing speed. The identification is based on the method of spectral dynamics analysis together with the integral correlation criteria (ICC). We compare the absorption spectral dynamics of a substance under analysis with the corresponding dynamics for a standard substance from database. For reliable and effective substance detection, we propose to use several ICC simultaneously in different time intervals, which contain not only the main pulse of the reflected THz signal, but also the sub-pulses. This way, one can detect and identify the substance in the sample with high probability. As examples of identification, we used the THz signals reflected from the plastic explosive PWM C4 with both rough and concave surface. We show that the main pulse, reflected from the inhomogeneous surface of the sample, contains information about its absorption frequencies.


Electric field control of the magnetocaloric effect.
Through strain-mediated magnetoelectric coupling, it is demonstrated that the magnetocaloric effect of a ferromagnetic shape-memory alloy can be controlled by an electric field. Large hysteresis and the limited operating temperature region are effectively overcome by applying an electric field on a laminate comprising a piezoelectric and the alloy. Accordingly, a model for an active magnetic refrigerator with high efficiency is proposed in principle.


Personal control and stress and coping processes: a theoretical analysis.
Laboratory and field research indicates that the relationships between personal control and stress, coping, and adaptational outcomes are more complex than was once assumed. Believing that an event is controllable does not always lead to a reduction in stress or to a positive outcome, and believing that an event is uncontrollable does not always lead to an increase in stress or to a negative outcome. These complex relationships involving control are examined in the context of Lazarus's cognitive theory of stress and coping. The first part of the article elaborates this theory and shows how two forms of control, generalized beliefs about control and situational appraisals of control, fit into the overall model. Situational appraisals of control are explored in this section, including the question, Control over what? which must be addressed in order to explain some of the perplexing findings. The second part of the article draws on the theoretical formulation of stress and coping to examine three important issues: (a) how believing one has control in a stressful transaction can heighten threat, (b) the relationship between control and coping, and (c) pathways through which control can affect the adaptational outcomes of stressful encounters.


Management of acute cardiovascular complications in pregnancy.
The growing population of women with heart disease of reproductive age has been associated with an increasing number of high-risk pregnancies. Pregnant women with heart disease are a very heterogeneous population, with different risks for maternal cardiovascular, obstetric, and foetal complications. Adverse cardiovascular events during pregnancy pose significant clinical challenges, with uncertainties regarding diagnostic and therapeutic approaches potentially compromising maternal and foetal health. This review summarizes best practice for the treatment of common cardiovascular complications during pregnancy, based on expert opinion, current guidelines, and available evidence. Topics covered include heart failure (HF), arrhythmias, coronary artery disease, aortic and thromboembolic events, and the management of mechanical heart valves during pregnancy. Cardiovascular pathology is the leading cause of non-obstetric morbidity and mortality during pregnancy in developed countries. For women with pre-existing cardiac conditions, preconception counselling and structured follow-up during pregnancy are important measures for reducing the risk of acute cardiovascular complications during gestation and at the time of delivery. However, many women do not receive pre-pregnancy counselling often due to gaps in what should be lifelong care, and physicians are increasingly encountering pregnant women who present acutely with cardiac complications, including HF, arrhythmias, aortic events, coronary syndromes, and bleeding or thrombotic events. This review provides a summary of recommendations on the management of acute cardiovascular complication during pregnancy, based on available literature and expert opinion. This article covers the diagnosis, risk stratification, and therapy and is organized according to the clinical presentation and the type of complication, providing a reference for the practicing cardiologist, obstetrician, and acute medicine specialist, while highlighting areas of need and potential future research.


[Can deliveries at risk be selected at smaller delivery units?].
In order to explore the possibility of converting a delivery unit at a small hospital to a maternity home, we examined the medical records of those women who delivered by Caesarean section, forceps or vacuum extraction at Lofoten hospital during 1995. How many of these women might it have been necessary to transfer to an obstetrical department if Lofoten hospital had been a maternity home caring for low risk deliveries (primipara and multipara)? Out of a total of 271 deliveries (primiparas 98), 49 women delivered by Caesarean section (n = 35), forceps (n = 5) or vacuum extraction (n = 9). Using risk assessment, 22 women (45%) would have been selected for antenatal transfer, and 20 (41%) for intrapartum transport. For seven women no transfer would have been possible. These women would have delivered locally by vacuum extraction. Primipara versus multipara had a relative risk of 2.8 for Caesarean section or assisted vaginal delivery. It is estimated that 8-9% of the women would be selected prenatally for planned delivery at a hospital unit and that 7-8% would be transferred in labour if primiparas delivered at the maternity home. If primiparas were excluded, the proportions would be 41% and 1-2% respectively. In 1997 the delivery unit at Lofoten hospital was temporarily converted to a maternity home for a period of two years.


Thermal coronary angiography in pediatric coronary artery bypass grafting.
A 2-year-old boy was referred to our institution for treatment of coronary artery obstruction after an arterial switch operation (ASO). We performed a pediatric coronary artery bypass graft (CABG) with skeletonized left internal thoracic artery (LITA). The patient was 88 cm tall and weighed 11 kg. The left anterior descending (LAD) coronary artery was also identified about 1 mm in diameter. Anastomotic failure of imposed stricture was detected with an infrared camera (IRIS-V, VERITAS, Tokyo, Japan). In the situation of CABG, thermal coronary angiography (TCA) is very useful to reveal satisfactory blood flow into the left coronary system during this procedure.


Homicidal Ideation and Individuals on the Autism Spectrum.
Interest in the relationship between autism and violence has increased in recent years; however, no link has clearly been established between them. Researchers remain curious if autistic people with certain traits (e.g., a history of trauma) are at greater risk of violence than those individuals with autism alone. In this article, we detail two individuals with homicidal ideation (HI) admitted to inpatient psychiatric units who were found to have a diagnosis of autism without language impairment. These cases illustrate the need for mental health providers to consider autism in their differential diagnosis when evaluating an individual with HI. Broadly, we consider how an autistic individual could be susceptible to developing HI and explore treatments specific to autistic individuals that may be helpful in such cases.


Fabrication of Wettability Mesh with Quasi-Rectangular-Restraining Capacity to Water.
A water droplet placed on a surface is usually round owing to surface tension. Restraining a droplet to a rectangle shape has been rarely reported. Herein, we fabricated three meshes with diverse wettability including ordinary mesh, superhydropilic mesh, and quasi-rectangular-restraining mesh. The profiles of water droplets on these three meshes were entirely different from the top view, especially for the quasi-rectangular-restraining mesh, which enables the water droplet on it to achieve the rectangular shape. The surface morphologies and chemical compositions of the meshes were characterized by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. Moreover, the influences of processing parameters of the quasi-rectangular-restraining mesh on the quasi-rectangular quality of the water droplet on it were investigated to obtain the relatively optimum processing parameters. The dynamic properties of water droplets on the three meshes were compared, and forces acting on the water droplets during the spreading and shrinking processes on the three meshes were qualitatively analyzed. Additionally, we studied the influences of falling height and water volume on the quasi-rectangular quality of the water droplet on the quasi-rectangular-restraining mesh. Water droplets on the quasi-rectangular-restraining mesh demonstrated good stability under vibration and the droplet could maintain the quasi-rectangular quality on the quasi-rectangular-restraining mesh for about 7 days, revealing a good durability. Further, the large-scaled fabrication of the quasi-rectangular-restraining mesh was realized.


The pros and cons of immunisation -- Paper two: the importance of immunisation.
Like other medicine, all vaccines have some side effects or complications; in general the incidence and severity of complications is lower than for pharmaceuticals. When considered on a population basis, the incidence of serious complications of vaccination is minute, when compared with the outcome of natural infection. Enlightened governments, which promote immunisation as a means of minimising the impact of infectious diseases in their communities, also accept the responsibility for any adverse events which can be demonstrated to be vaccine related, and provide compensation and care for people who are affected.


Targeted modifications in adeno-associated virus serotype 8 capsid improves its hepatic gene transfer efficiency in vivo.
Recombinant adeno-associated virus vectors based on serotype 8 (AAV8) have shown significant promise for liver-directed gene therapy. However, to overcome the vector dose dependent immunotoxicity seen with AAV8 vectors, it is important to develop better AAV8 vectors that provide enhanced gene expression at significantly low vector doses. Since it is known that AAV vectors during intracellular trafficking are targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal machinery, we modified specific serine/threonine kinase or ubiquitination targets on the AAV8 capsid to augment its transduction efficiency. Point mutations at specific serine (S)/threonine (T)/lysine (K) residues were introduced in the AAV8 capsid at the positions equivalent to that of the effective AAV2 mutants, generated successfully earlier. Extensive structure analysis was carried out subsequently to evaluate the structural equivalence between the two serotypes. scAAV8 vectors with the wild-type (WT) and each one of the S/T→Alanine (A) or K-Arginine (R) mutant capsids were evaluated for their liver transduction efficiency in C57BL/6 mice in vivo. Two of the AAV8-S→A mutants (S279A and S671A), and a K137R mutant vector, demonstrated significantly higher enhanced green fluorescent protein (EGFP) transcript levels (~9- to 46-fold) in the liver compared to animals that received WT-AAV8 vectors alone. The best performing AAV8 mutant (K137R) vector also had significantly reduced ubiquitination of the viral capsid, reduced activation of markers of innate immune response, and a concomitant two-fold reduction in the levels of neutralizing antibody formation in comparison to WT-AAV8 vectors. Vector biodistribution studies revealed that the K137R mutant had a significantly higher and preferential transduction of the liver (106 vs. 7.7 vector copies/mouse diploid genome) when compared to WT-AAV8 vectors. To further study the utility of the K137R-AAV8 mutant in therapeutic gene transfer, we delivered human coagulation factor IX (h.FIX) under the control of liver-specific promoters (LP1 or hAAT) into C57BL/6 mice. The circulating levels of h.FIX:Ag were higher in all the K137R-AAV8 treated groups up to 8 weeks post-hepatic gene transfer. These studies demonstrate the feasibility of the use of this novel AAV8 vectors for potential gene therapy of hemophilia B.


ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones.
Presynaptic active zones (AZs) are unique subcellular structures at neuronal synapses, which contain a network of specific proteins that control synaptic vesicle (SV) tethering, priming, and fusion. Munc13s are core AZ proteins with an essential function in SV priming. In hippocampal neurons, two different Munc13s-Munc13-1 and bMunc13-2-mediate opposite forms of presynaptic short-term plasticity and thus differentially affect neuronal network characteristics. We found that most presynapses of cortical and hippocampal neurons contain only Munc13-1, whereas ∼10% contain both Munc13-1 and bMunc13-2. Whereas the presynaptic recruitment and activation of Munc13-1 depends on Rab3-interacting proteins (RIMs), we demonstrate here that bMunc13-2 is recruited to synapses by the AZ protein ELKS1, but not ELKS2, and that this recruitment determines basal SV priming and short-term plasticity. Thus, synapse-specific interactions of different Munc13 isoforms with ELKS1 or RIMs are key determinants of the molecular and functional heterogeneity of presynaptic AZs.


[Experience with implantation of posterior chamber lenses at the Ophthalmology Clinic of the Martin Medical School Hospital].
The authors refer to their experience with implantation of 23 IOL following the extraction of cataract, using the Baikoff's method (envelope technique). The ratio men:women in the treated group of patient was 13:10. In 19 patients the resultant vision acuity achieved the value of 6/18, or even better. Postoperative complications were represented by a temporary increase of intraocular pressure (occurred in 3 patients), fibrin reaction (occurred in 5 patients), deformation of the pupil (occurred in 3 patients) and vitreous body hemorrhage (occurred in 1 patient). The observation period lasted 3-6 months. The reason of deteriorated vision acuity which occurred in 4 cases was the presence of glaucoma chronicum simplex and degeneratio maculae luteae. (Tab. 3, Ref. 5.)


Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study.
North American health authorities recommend 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in the circulation. The biological effects of unmetabolized folic acid are unknown. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins; however, it has yet to be evaluated during pregnancy. This double-blind, randomized trial will recruit 60 pregnant women aged 19-42 years. The women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16 weeks. The trial will be initiated at 8-21 weeks' gestation (after neural tube closure) to reduce the risk of harm should (6S)-5-methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. The extent to which the change in primary outcomes from baseline to endline differs between treatment groups, controlling for baseline level, will be estimated using linear regression. Participants will have the option to continue supplementing until 1 week postpartum to provide a breastmilk and blood sample. Exploratory analyses will be completed to evaluate breastmilk and postpartum blood folate concentrations. This proof-of-concept trial is needed to obtain estimates of the effect of (6S)-5-methyltetrahydrofolic acid compared to folic acid on circulating biomarkers of folate status during pregnancy. These estimates will inform the design of a definitive trial which will be powered to assess whether (6S)-5-methyltetrahydrofolic acid is as effective as folic acid in raising blood folate concentrations during pregnancy. Ultimately, these findings will inform folate supplementation policies for pregnant women. ClinicalTrials.gov, ID: NCT04022135. Registered on 14 July 2019.


Sympathetic ophthalmia: induced by vitrectomy not by trauma.
A case of sympathetic ophthalmia that occurred after corneoscleral laceration due to blunt trauma and after vitrectomy was encountered, and the patient was treated without enucleation of the exciting eye; this is the sixteenth case of sympathetic ophthalmia reported to occur after vitrectomy. In the reported cases including the present one, the intervals between the primary trauma or primary intraocular surgery and secondary vitrectomy and the onset of sympathetic ophthalmia were compared with those in patients who suffered from this disease without vitrectomy. The statistical analysis by the probit method revealed that the onset of sympathetic ophthalmia was critically influenced by the secondarily delivered operation, ie, vitrectomy (P less than 0.05).


Effects of alcohol and trait anger on physical aggression in men.
According to recent theoretical models, the alcohol-aggression link is predicated on the interaction among many variables, including the drinker's personality. The few studies that investigated effects of personal dispositions on alcohol-related aggression have been inconclusive, possibly because the role of dispositions related to affect were largely ignored. As such, the purpose of this study was to investigate the interactive effect of alcohol and trait anger on physical aggression. Participants were 136 male social drinkers who reported high, moderate, and low levels of trait anger and were nonrandomly assigned to an "alcohol" or "no-alcohol" control beverage group. Participants competed in an aggression paradigm in which electric shocks were received from and administered at will to a fictitious opponent during a competitive task. Shock intensity, duration, and proportion of highest shock served as indexes of aggression. Intoxicated participants with moderate trait anger selected higher shock intensity and had a greater proportion of highest shock, compared with their sober counterparts. Within the alcohol group, high- and moderate-anger participants were more aggressive than low-anger participants. Intoxicated participants selected longer shock durations following both low and high provocation, and they evinced a greater increase in shock duration from low to high provocation than their sober counterparts. Independent of beverage group, men who reported a high or moderate level of trait anger displayed more aggression on all measures, compared with those who reported low anger disposition. The present findings suggest that individuals who report low levels of trait anger may be more resistant to the potentiating effects of alcohol on aggression and that the effects of alcohol on aggression may be most pronounced in men who have a moderate level of trait anger. Furthermore, independent of intoxication, trait anger appears to be a risk factor for physical aggression in men.


Selected Risk Nutritional Factors for Chemotherapy-Induced Polyneuropathy.
The present study seeks to identify the nutritional risk factors involved in the development of neuropathies induced by chemotherapeutic treatments. Unlike the gastrointestinal or hematological adverse effects of chemotherapy there is no protective treatment strategy for polyneuropathy. The aim of this study was to find possible deficiencies in nutritional factors, which can be used for supplementation in the future for prevention of chemotherapy-induced neuropathy development. We analyzed 70 patients undergoing paclitaxel chemotherapy and evaluated the risk factors involved in chemotherapy-induced peripheral neuropathy (CIPN). Several risk factors were considered in the development of CIPN, including deficiency of vitamin B1, B6, and D and fatty acids. The occurrence of CIPN complication in 60% cases was observed. We found significant differences in vitamin D and saturated fatty acid concentration. Vitamin D levels in the group without CIPN were estimated to be 38.2 (24.95, 47.63) nmol/L, whereas in the group with CIPN it was determined to be 25.6 (19.7, 32.55) nmol/L, p = 0.008. The level of total saturated fatty acids in the group without CIPN was of 32.613 Area % (31.322; 36.262), whereas in the group with CIPN it was of 34.209 Area % (32.86; 39.386), p = 0.01. The obtained results suggest a diet lower in saturated fatty acid content during chemotherapy. The most significant finding was that supplementation of vitamin D before chemotherapy could be an efficient neuroprotective in CIPN prophylaxis, as significantly lower levels 25OH derivative of vitamin D were observed in the CIPN group throughout the study period.


The value of believing in free will: A prediction on seeking and experiencing meaning in life.
Despite abundant philosophical pondering and experiential evidence demonstrating the need for freedom in leading a meaningful life, the literature lacks an investigation of whether and how free will beliefs contribute to one's meaningful life as an antecedent variable. Based on the coupling of the life-affirming hypothesis and Chinese culture, we used a manipulation experiment (Study 1, n = 242) and a two-wave longitudinal study (Study 2, n = 378) to test the potential causality between laypeople's daily beliefs in free will and meaning in life (presence of and search for meaning) with two samples of Chinese undergraduates. The results show that belief in free will positively predicts the presence of meaning and search for meaning, immediately (Study 1) and 2 months later (Study 2). The present work corroborated that the belief in free will is an antecedent variable that imbues life with meaning and sparks actions seeking meaning, supporting the life-affirming hypothesis instead of the deficit-correcting hypothesis.


Inferring the strength of selection in Drosophila under complex demographic models.
Transposable elements (TEs) constitute a substantial fraction of the genomes of many species, and it is thus important to understand their population dynamics. The strength of natural selection against TEs is a key parameter in understanding these dynamics. In principle, the strength of selection can be inferred from the frequencies of a sample of TEs. However, complicated demographic histories, such as found in Drosophila melanogaster, could lead to a substantial distortion of the TE frequency distribution compared with that expected for a panmictic, constant-sized population. The current methodology for the estimation of selection intensity acting against TEs does not take into account demographic history and might generate erroneous estimates especially for TE families under weak selection. Here, we develop a flexible maximum likelihood methodology that explicitly accounts both for demographic history and for the ascertainment biases of identifying TEs. We apply this method to the newly generated frequency data of the BS family of non-long terminal repeat retrotransposons in D. melanogaster in concert with two recent models of the demographic history of the species to infer the intensity of selection against this family. We find the estimate to differ substantially compared with a prior estimate that was made assuming a model of constant population size. Further, we find there to be relatively little information about selection intensity present in the derived non-African frequency data and that the ancestral African subpopulation is much more informative in this respect. These findings highlight the importance of accounting for demographic history and bear on study design for the inference of selection coefficients generally.


Protein quality of anchovy, mackerel and canned sardine samples.
The protein nutritive value of anchovy, mackerel and canned sardine samples together with casein as a reference formulation were evaluated. Proximate composition, protein quality and protein digestibility were determined. Procedures for evaluation included Protein Efficiency Ratio (PER) using the rat bioassay and in vivo Apparent Digestibility (AD). Rats fed with canned sardine diet had the highest mean body weight (154.8±12.28g) while rats fed with anchovy diet had the lowest mean body weight (145.27±15.89g) with significant differences between all the groups. Mean body weight of rats fed with selected fish diet was higher compared to rats fed with casein diet. For PER value, canned sardine has the highest value (2.48), followed by anchovy (2.46) and mackerel (2.34). PER value for all selected fish is lower than that for casein (3.14). Mackerel had the highest value of in vivo AD (96.99%), followed by casein (96.96%), canned sardine (96.88%) and anchovy (91.29%). In conclusion, among the types of fish compared, sardine had the highest protein quality while mackerel showed the highest digestibility.


Predicting Acute and Post-Recovery Outcomes in Cerebral Malaria and Other Comas by Optical Coherence Tomography (OCT in CM) - A protocol for an observational cohort study of Malawian children.
Cerebral malaria (CM) remains a significant global health challenge with high morbidity and mortality. Malarial retinopathy has been shown to be diagnostically and prognostically significant in the assessment of CM. The major mechanism of death in paediatric CM is brain swelling. Long term morbidity is typically characterised by neurological and neurodevelopmental sequelae. Optical coherence tomography can be used to quantify papilloedema and macular ischaemia, identified as hyperreflectivity. Here we describe a protocol to test the hypotheses that quantification of optic nerve head swelling using optical coherence tomography can identify severe brain swelling in CM, and that quantification of hyperreflectivity in the macula predicts neurodevelopmental outcomes post-recovery. Additionally, our protocol includes the development of a novel, low-cost, handheld optical coherence tomography machine and artificial intelligence tools to assist in image analysis.


A new type of mobile dental clinic developed following the Lebanon War, 1982.
A two-tier emergency dental services delivery system was developed following the October 1973 War, based on large mobile dental clinics (definitive restorations) and portable field units (emergency treatments). The increased demand for definitive restorations at the front lines, the mountainous terrain, and the extreme climatic conditions encountered during the Lebanon War, 1982, necessitated the development of a third alternative. A standard, compact module, either truck-mounted or helicopter-lifted, was outfitted as a fully equipped dental clinic according to Dental Corps specifications.


A kind of synthetic nanopillar arrays for studying single biomolecule.
The anodic aluminum oxide (AAO) template with ordered pores was firstly fabricated in oxalic acid solutions using two-step anodization method. Then, a layer of polymethylmethacrylate (PMMA) was uniformly laid on one surface of the AAO template by a Spin-Coater, then baked and cooled them, after that, the H3PO4 solution was utilized to dissolve the residual aluminum and barrier layer, as the result, the functional nanopillar arrays were achieved. Finally, the morphology of the functional PMMA nanopillars was examined with the Scanning Electron Microscope (SEM) and the properties were discussed. The functional nanopillar arrays could be applied to the micro and nano-scale devices as the sensors for the biological, chemical and single molecular detection.


Unusual Polyoxygenated Monoterpenes from the Antarctic Alga Pantoneura plocamioides
Six new polyoxygenated marine monoterpenes have been isolated from the Antarctic alga Pantoneura plocamioides. The structure and relative stereochemistry of these compounds, denominated pantopyranoids A-C (1-3), and pantoisofuranoids A-C (4-6) were determined on basis of spectroscopic evidence.


Gingival recession in school kids aged 10-15 years in Udaipur, India.
The study aimed to determine the incidence of gingival recession in the mandibular central incisor region among school children aged 10-15 years in Udaipur (India). A sample of 1800 males and female kids were examined in a mobile dental unit. World Health Organisation (WHO) rules and standards were followed. Gingival recession, when compared, with respect to age, mean clinical crown length, anterior crowding and frenal involvement was significant (p less than 0.00) with respect to affected teeth.


Phosphatidylcholine hydrolysis is required for pancreatic cholesterol esterase- and phospholipase A2-facilitated cholesterol uptake into intestinal Caco-2 cells.
Pancreatic secretion is required for efficient cholesterol absorption by the intestine, but the factors responsible for this effect have not been clearly defined. To identify factors involved and to investigate their role in cholesterol uptake, we studied the effect of Viokase(R), a porcine pancreatic extract, on cholesterol uptake into human intestinal Caco-2 cells. Viokase is capable of facilitating cholesterol uptake into these cells such that the level of uptake is 5-fold higher in the presence of solubilized Viokase. This stimulation is time-dependent and is dependent on the presence of bile salt. However, bile salt-stimulated pancreatic cholesterol esterase, which has been proposed to mediate cholesterol uptake, is not fully responsible. The major cholesterol transport activity was purified and identified as pancreatic phospholipase A2. Anti-phospholipase A2 antibodies abolished virtually all of the phospholipase A2 and cholesterol transport activity of solubilized Viokase. We demonstrate that both phospholipase A2 and cholesterol esterase increase cholesterol uptake by hydrolyzing the phosphatidylcholine that is used to prepare the cholesterol-containing micelles. In the absence of cholesterol esterase or phospholipase A2, uptake of cholesterol from micelles containing phosphatidylcholine is not as efficient as uptake from micelles containing phospholipase A2-hydrolytic products. These results indicate that phospholipase A2 may mediate cholesterol absorption by altering the physical-chemical state of cholesterol within the intestine.


Development and Pilot Analysis of the Bruise Visibility Scale.
The accuracy of assessing and documenting injuries is crucial to facilitate ongoing clinical care and forensic referrals for victims of violence. The purpose of this cross-sectional, pilot study was to evaluate the inter-rater reliability and criterion validity of a newly developed Bruise Visibility Scale (BVS). Methods: The instrument was administered to a diverse sample (n = 30) with existing bruises. Bruises were assessed under fluorescent lighting typical of an examination room by three raters who were randomly selected from a pool of eight experienced clinical nurses. Colorimetry values of the bruise and surrounding tissue were obtained using a spectrophotometer. Results: The BVS demonstrated good single (ICC = 0.71, 95% CI = 0.54 - 0.84) and average agreement (ICC = 0.88, 95% CI = 0.78 - 0.94) between raters. A significant, positive moderate correlation was found between mean BVS scores and overall color difference between the bruise and surrounding skin (Pearson's r = 0.614, p < 0.001). Conclusion: With further research, the BVS has the potential to be a reliable and valid tool for documenting the degree of clarity in bruise appearance.


Binding of transmissible gastroenteritis coronavirus to brush border membrane sialoglycoproteins.
Transmissible gastroenteritis coronavirus (TGEV) is a porcine pathogen causing enteric infections that are lethal for suckling piglets. The enterotropism of TGEV is connected with the sialic acid binding activity of the viral surface protein S. Here we show that, among porcine intestinal brush border membrane proteins, TGEV recognizes a mucin-type glycoprotein designated MGP in a sialic acid-dependent fashion. Virus binding assays with cryosections of the small intestine from a suckling piglet revealed the binding of TGEV to mucin-producing goblet cells. A nonenteropathogenic mutant virus that lacked a sialic acid binding activity was unable to bind to MGP and to attach to goblet cells. Our results suggest a role of MGP in the enteropathogenicity of TGEV.


Evaluation of Moral Reasoning Skills among Dental Students in the Makkah Region, Saudi Arabia.
One of the main roles of healthcare educators is to prepare students to make the right ethical decisions. This study evaluated the moral reasoning levels of dental students according to Kohlberg's six-stage moral development system. This cross-sectional study was conducted in three dental schools in the Makkah region. Senior-year students completed the self-administered Socio-moral Reflection Objective Measure (SROM), which consists of hypothetical moral dilemmas and options that mirror individual reasoning possibilities. SROM results were matched to Kohlberg's six-stage moral development system and associations with demographic variables and perceptions of educational context variables assessed. One hundred and eighty-eight senior students (mean age 23 ± 1.1 years) completed the SROM. Only 34.6% (n = 44) students reached stage four (morality of law and duty to the social order), while most students (63.8%; n = 81) were at stage three (morality of mutual interpersonal expectations); 1.6% (n = 2) were at stage two (the instrumental relativist orientation). No subject achieved stage 5. Attainment of moral reasoning was not associated with demographic or perception of educational context variables. Students demonstrated a relatively low level of moral reasoning. Healthcare educators must review curricula to provide focused training for students to cultivate their moral reasoning skills. Further studies are also needed to confirm and explain this low moral reasoning level in dental students.


Onset of inflammatory bowel diseases during combined alpha-interferon and ribavirin therapy for chronic hepatitis C: report of two cases.
We report two patients who developed an inflammatory bowel disease (IBD) shortly after beginning combined alpha-interferon and ribavirin treatment for HCV-related chronic hepatitis. The previous clinical history was negative for IBD in both patients, who developed diarrhoea and rectal bleeding 10 days and 6 months, respectively, after the initiation of therapy. The history, therapeutic management and the possible causal relationships of these cases are discussed.


Activated Sludge and other Aerobic Suspended Culture Processes.
This is a literature review for the year 2014 and contains information specifically associated with suspended growth processes including activated sludge and sequencing batch reactors. This review is a subsection of the treatment systems section of the annual literature review. The review encompasses modeling and kinetics, nutrient removal, system design and operation. Compared to past reviews, many topics show increase in activity in 2014. These include, nitrogen and phosphorus control, fate and effect of xenobiotics, industrial wastes treatment, and some new method for the determination of activated sludge. These topics are referred to the degradation of constituents in activated sludge. Other sections include population dynamics, process microbiology of activated sludge, modeling and kinetics. Many of the subsections in the industrial wastes: converting sewage sludge into fuel gases, thermos-alkali hydrolysis of Waste Activated Sludge (WAS), sludge used as H2 S adsorbents were also mentioned in this review.


Open Globe Injuries From Garage Door Springs.
We describe seven patients who were attempting to repair their garage door when a spring dislodged at high velocity, resulting in open globe injury. All patients were seen at Massachusetts Eye and Ear between the years 2008 and 2023. Their final visual acuities ranged from 20/125 to no light perception. Open globe injury appears to be a risk of attempts to repair a garage door by people who are inexperienced in doing so. [Ophthalmic Surg Lasers Imaging Retina 2023;54:666-669.].


A Pilot Randomized Controlled Clinical Trial to Assess Tolerance and Efficacy of Navy Bean and Rice Bran Supplementation for Lowering Cholesterol in Children.
Background: Navy beans and rice bran demonstrate efficacy to regulate serum cholesterol in hypercholesterolemic adults; however, the cardiovascular disease (CVD) protective properties of these foods in children are unknown and merit investigation. Objective: The objectives were to determine whether cooked navy bean powder (NBP) and/or heat-stabilized rice bran (RB) supplementation is tolerable, improves dietary fiber intake in children, and modulates lipid profiles. Methods: Children aged 8 to 13 years at risk for CVD due to abnormal lipids were recruited. Elevated cholesterol levels were defined as total cholesterol ≥180 mg/dL and high-density lipoprotein (HDL) <60 mg/dL; low-density lipoprotein (LDL) ≥100 mg/dL and HDL <60 mg/dL; or non-HDL >100 mg/dL and HDL <60 mg/dL. Participants completed a pilot 4-week, randomized controlled, 4-arm dietary intervention. They consumed study-provided muffins or a smoothie daily that included 0 g NBP or RB (control), 17.5 g NBP, 15 g RB, or a combination 9 g NBP + 8 g RB. Fasting blood was collected at baseline and week 4. Participants also completed 3-day food logs and gastrointestinal health questionnaires. Thirty-eight children completed the trial (n = 9 control, n = 10 NBP, n = 9 RB, and n = 10 NBP + RB groups). Only 3 participants withdrew due to noncompliance of required food consumption. Participants in the intervention groups significantly increased intake of NBP and RB at week 4 (p≤.01). The NBP and NBP + RB groups increased total fiber intake from baseline to week 4 (p=.02 and p=<.01, respectively). HDL-cholesterol was higher in NBP-group participants compared to control at week 4 (P = .02). Conclusion: Increasing NBP and/or RB intake is tolerable for children, and our findings suggest higher daily intakes are needed for a longer duration to induce favorable changes across multiple serum lipid parameters.


Surgical patch angioplasty of the left main coronary artery.
Isolated ostial stenosis of the left main coronary artery (LMCA) is rare, occurring in <1% of the patients undergoing coronary angiography. Surgical patch angioplasty (SPA) offers an alternative to conventional coronary artery bypass grafting (CABG) in such cases and is advantageous in restoring more physiological myocardial perfusion, maintaining ostial patency and preserving conduit material. However, a number of early technical failures and high perioperative mortality have limited the generalized uptake of this procedure, and only recently have advances in myocardial protection and novel surgical approaches to the LMCA resulted in a resurgence of the technique. A systematic literature search identified 45 studies incorporating 478 patients undergoing SPA. A variety of patch materials were used, including the pericardium, saphenous vein and internal mammary and pulmonary arteries. Patients were followed up for a mean of 54.4 months. The 30-day mortality was 1.7% and cardiac specific mortality 3.3% at last follow-up. Encouragingly, 92.4% of reported cases (n = 182) showed complete angiographic patency at last follow-up. Our results indicate that SPA may be a viable alternative to CABG in the surgical management of isolated ostial LMCA stenosis. However, no randomized trials have been performed, and it is clear that careful patient selection is essential in minimizing morbidity and mortality in the short- and long-term. Further research is required to allow a direct comparison of SPA to techniques with a more substantial evidence base such as CABG and percutaneous coronary intervention, and to define the optimal patch graft material, elucidating that any beneficial effects arterial patches may have on long-term patency.


Unusual thermodynamic properties and nonergodicity in ferroelectric superlattices.
The properties of [Pb(Zr(1-x(1))Ti(x(1)))O(3)](n)/[Pb(Zr(1-x(2))Ti(x(2)))O(3)](n) superlattices, with a 2n period, are simulated using an ab initio based approach. The x(1) and x(2) compositions are chosen to be located across the morphotropic phase boundary of the corresponding disordered alloys, while the (x(1)+x(2))/2 average composition lies inside this boundary. These superlattices exhibit an unusual thermodynamic phase transition sequence, including a triclinic ground state. They also have the kind of peculiar free-energy landscape yielding nonergodicity. The effects responsible for these anomalies are discussed.


Analysis of the effects of calcium or magnesium on voltage-clamp currents in perfused squid axons bathed in solutions of high potassium.
Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15-30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system.


The risk of premarital first pregnancy among metropolitan-area teenagers: 1976 and 1979.
Among sexually active teenage women living in metropolitan areas of the United States, the risk of premarital pregnancy within two years of first sexual intercourse rose from 32 percent in 1976 to 36 percent in 1979. As of 1979, 33 percent of unmarried white teenagers, and 43 percent of unmarried black teenagers, had conceived within 24 months of becoming sexually active. The increase in pregnancy risk between 1976 and 1979 was relatively greater for whites than for blacks at three, six and 12 months after first intercourse. The reverse was true at later intervals. The risk of pregnancy is disproportionately concentrated in the early months of sexual activity. Forty-five percent of all premarital pregnancies among those interviewed in 1979 had been conceived within the first six months of sexual activity, and 36 percent had been conceived within three months. In 1976, 27 percent of teenagers who had become sexually active before the age of 15 were premaritally pregnant within two years. By 1979, this proportion had risen to 41 percent--a 52 percent increase in the risk that accounts for almost all of the total three-year increase in premarital pregnancies among sexually active teenagers. The most pronounced increase in risk of pregnancy was registered among whites who became sexually active when they were younger than 15. Their 24-month probability of conception rose from 20 percent in 1976 to 39 percent by 1979. Levels of risk for unwed teenagers who initiated intercourse at ages 15-19 increased relatively little.(ABSTRACT TRUNCATED AT 250 WORDS)


[An example of rehabilitation of speech by mediation-techniques in aphasia].
In a case of severe aphasia it was attempted to use a mediation technique. During several months there was no improvement in speech by using the usual techniques. The patient had to learn several gestures that corresponded to different letters. This technique result in a considerable speech improvement. It is discussed which mechanisms are possibly involved in the rehabilitation process; the practical importance of the mediation technique is suggested.


Development and Validation of the Suprathreshold Stochastic Resonance-Based Image Processing Method for the Detection of Abdomino-pelvic Tumor on PET/CT Scans.
The detection of abdomino-pelvic tumors embedded in or nearby radioactive urine containing 18F-FDG activity is a challenging task on PET/CT scan. In this study, we propose and validate the suprathreshold stochastic resonance-based image processing method for the detection of these tumors. The method consists of the addition of noise to the input image, and then thresholding it that creates one frame of intermediate image. One hundred such frames were generated and averaged to get the final image. The method was implemented using MATLAB R2013b on a personal computer. Noisy image was generated using random Poisson variates corresponding to each pixel of the input image. In order to verify the method, 30 sets of pre-diuretic and its corresponding post-diuretic PET/CT scan images (25 tumor images and 5 control images with no tumor) were included. For each sets of pre-diuretic image (input image), 26 images (at threshold values equal to mean counts multiplied by a constant factor ranging from 1.0 to 2.6 with increment step of 0.1) were created and visually inspected, and the image that most closely matched with the gold standard (corresponding post-diuretic image) was selected as the final output image. These images were further evaluated by two nuclear medicine physicians. In 22 out of 25 images, tumor was successfully detected. In five control images, no false positives were reported. Thus, the empirical probability of detection of abdomino-pelvic tumors evaluates to 0.88. The proposed method was able to detect abdomino-pelvic tumors on pre-diuretic PET/CT scan with a high probability of success and no false positives.


Metabolite identification of AZD8055 in Sprague-Dawley rats after a single oral administration using ultra-performance liquid chromatography and mass spectrometry.
AZD8055 is an ATP-competitive specific dual mTOR inhibitor and exhibited potent antitumor activity on several types of solid tumors. However, the metabolism of AZD8055 in the body still remains unknown. In this study, metabolite identification of AZD8055 was performed using ultra high-performance liquid chromatography-ion trap mass spectrometry (UHPLC-IT-MS) through both in vitro and in vivo approaches using rat liver microsomes (RLMs) and rat plasma, urine and feces, respectively. A total of eight putative metabolites (five phase I and three phase II) were identified, and a tentative metabolic pathway was suggested for the first time. Considering the accurate mass and mass fragmentations of the detected metabolites, their plausible structures were suggested. Demethylation, hydroxylation, oxidation and morpholine ring opening were the major biotransformation processes for the phase-I metabolism, while phase-II metabolites were merely generated by the glucuronide conjugation reaction. The cumulative excretion of AZD8055 in urine and feces was 0.13% and 1.11% of the dose, respectively. When the semi-quantitative analysis of the metabolites was performed using UHPLC-MS/MS (ultra-performance liquid chromatography tandem mass spectrometry) to evaluate the overall trend of metabolites formation and excretion, AZD8055 was excreted more in the form of the metabolites than itself and their formation was very fast. Therefore it was presumed that biotransformation was playing a crucial role in its elimination. Ultimately, this study provides novel insights regarding the in vitro and in vivo biotransformations of AZD8055. Further investigations of metabolites of this potent anti-cancer compound could be beneficial for the antitumor drug design and development process.


Solute carrier family 35 member A2 (SLC35A2) is a prognostic biomarker and correlated with immune infiltration in stomach adenocarcinoma.
Solute carrier family 35 member A2 (SLC35A2) located on the X chromosome is considered involved in the UDP-galactose transport from cytosol to Golgi apparatus and endoplasmic reticulum. It has been reported that the SLC35A2 expression is associated with carcinogenesis in recent studies, however, its specific roles in cancer progression have not been exhaustively elucidated. Herein, a system analysis was conducted to evaluate the role of SLC35A2 in prognostic, and immunology in stomach adenocarcinoma (STAD). The TIMER, GEPIA, UALCAN, Kaplan-Meier Plotter were employed to explore the SLC35A2 expression pattern and prognostic value in STAD. Genomic alterations were searched through the MEXPRESS and cBioPortal platforms. The LinkedOmics, GEPIA and Metascape databases were employed to explore the biological processes. The TIMER and TISIDB websites were utilized to investigate the relationships between SLC35A2 expression and immune cell infiltration. The associations between SLC35A2 expression and tumor mutational burden (TMB), microsatellite instability (MSI) in pan-cancer were explored using the SangerBox database. Compared to the normal gastric mucosa, SLC35A2 expression was significantly increased in STAD tissues, accompanied by the robust relationships with tumor grade, histological subtypes, TP53 mutation status, TMB and prognosis. SLC35A2 and its co-expression genes played the primarily roles in purine metabolism and purinosome, including the asparagine N-linked glycosylation, protein processing in endoplasmic reticulum, regulation of transcription involved in G1/S transition of mitotic cell cycle, with the potential to participate in the regulation of VEGFA-VEGFR2 signaling pathway. Concurrently, SLC35A2 expression was correlated with macrophages and CD4+T lymphocytes infiltration in STAD. Our study has proposed that SLC35A2 correlated with immune cell infiltration could serve as a prognostic biomarker in STAD.


Mucinous Adenocarcinoma of the Endometrium Compared With Endometrioid Endometrial Cancer: A SEER Analysis.
Mucinous endometrial cancer (MEC) is a rare histologic subtype of endometrial cancers. The purpose of this study is to compare the outcomes of patients with MEC with patients with endometrioid endometrial cancers (EEC), and to determine whether there are significant clinicopathologic differences between these tumors. Surveillance, Epidemiology, and End Results (SEER) Program data for 1988 to 2009 was reviewed. Demographic and clinical data were compared. The impact of histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. The study group consisted of 104,659 women, 103,097 (98.5%) had EEC and 1562 (1.5%) MEC. The mean age at diagnosis for EEC and MEC was 62 and 63.4, respectively (P<0.001). MEC tumors were more frequently classified as grade 1 (51.3% vs. 44%; P<0.001). In patients with MEC, a higher rate of pelvic lymph node metastasis (16.3% vs. 10.4%; P<0.001) was noted, but not para-aortic lymph node metastasis (5.1% vs. 4%; P=0.1). After adjusting for race, period of diagnosis, SEER registry, marital status, stage, age, surgery, radiotherapy, grade, histology, and lymph node dissection, there was no difference in survival between MEC and EEC (hazard ratio 0.90; 95% confidence interval, 0.78-1.05). Mucinous histology does not significantly affect survival when compared with endometrioid histology in endometrial cancer. Patients with MEC were more likely to have positive pelvic lymph nodes at the time of surgery.


Keep an eye out for tubulo-interstitial nephritis.
Acute tubulo-interstitial nephritis and uveitis syndrome (TINU) is a rare disease, generally presenting in young women. We describe a 16-year-old Turkish girl with aspecific symptoms and elevated serum creatinine. Further, she complained about a burning pain in her left eye. Renal biopsy revealed acute TIN. Other conditions were excluded and TINU was diagnosed.


Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma.
No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC). This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive, completely resected thoracic ESCC patients. We conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d. Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 (86.0%) patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group (P=0.006). The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group (P=0.013). Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005). Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.


Showing the Way: Oncolytic Adenoviruses as Chaperones of Immunostimulatory Adjuncts.
Oncolytic adenoviruses (OAds) are increasingly recognized as vectors for immunotherapy in the treatment of various solid tumors. The myriads of advantages of using adenovirus include targeted specificity upon infection and selective replication, which lead to localized viral burst, exponential spread of OAds, and antitumor effect. OAds can also induce a strong immune reaction due to the massive release of tumor antigens upon cytolysis and the presence of viral antigens. This review will highlight recent advances in adenoviral vectors expressing immunostimulatory effectors, such as GM-CSF (granulocyte macrophage colony-stimulating factor), interferon-α, interleukin-12, and CD40L. We will also discuss the combination of OAds with other immunotherapeutic strategies and describe the current understanding of how adenoviral vectors interact with the immune system to eliminate cancer cells.


Associations between patterns of modifiable risk factors in mid-life to late life and longevity: 36 year prospective cohort study.
To examine the associations between patterns of mid-life to late life modifiable risk factors and longevity. Prospective cohort study. Data collected from the Nurses' Health Study starting in 1984 and the Health Professionals Follow-up Study starting in 1986. 85 346 participants from the Nurses' Health Study and the Health Professionals Follow-up Study. Death from any cause by 31 October 2020 for the Nurses' Health Study and Health Professionals Follow-up Study. Risk factors investigated were body mass index, physical activity, alcohol intake, smoking status, and quality of diet. Trajectories of each risk factor and trajectories of changes in the risk factor were identified from baseline with smoothing mixture models, and the joint group memberships of participants was used to most efficiently capture patterns of the factor over time. For each risk factor, three trajectories (patterns with high, medium, and low values) and three trajectories of change in the risk factor (patterns with increase, no change, and decrease in the factor from baseline) were assumed, giving nine joint patterns: high-stable, high-increase, high-decrease, medium-stable, medium-increase, medium-decrease, low-stable, low-increase, and low-decrease. Associations between patterns of modifiable risk factors and longevity (age at death ≥85 years) and life expectancy were examined with logistic regression and accelerated failure time models, respectively. The analysis included 85 346 participants, with 46 042 participants achieving longevity and 25 322 participants achieving healthy longevity (those who did not have a diagnosis of cardiovascular disease, type 2 diabetes, or cancer). Mean age at baseline was 56 years (standard deviation 5 years). Maximum longevity was achieved in participants with a low-stable pattern for body mass index (compared with a medium-stable pattern, odds ratio of longevity of 1.05, 95% confidence interval 1.00 to 1.10); those with a medium-increase pattern for physical activity (compared with a medium-stable pattern, odds ratio 1.08, 1.01 to 1.15); those with a medium-stable pattern for alcohol intake (high-increase v medium-stable pattern, odds ratio 0.83, 0.74 to 0.93); those who never smoked (low-stable v medium-stable pattern, odds ratio 3.09, 2.84 to 3.37); and those who with a high-increase pattern for quality of diet (compared with a medium-stable pattern, odds ratio 1.09, 1.01 to 1.18). The associations between each factor and life expectancy and healthy longevity (no diagnosis of cardiovascular disease, type 2 diabetes, or cancer) were similar to those for longevity. During mid-life and late life, maximum longevity was achieved in participants who maintained a normal body mass index, never smoked, ate a healthy diet, and had physical activity levels and alcohol consumption that met public health recommendations.


Plasmodium falciparum glutamate dehydrogenase a is dispensable and not a drug target during erythrocytic development.
Plasmodium falciparum contains three genes encoding potential glutamate dehydrogenases. The protein encoded by gdha has previously been biochemically and structurally characterized. It was suggested that it is important for the supply of reducing equivalents during intra-erythrocytic development of Plasmodium and, therefore, a suitable drug target. The gene encoding the NADP(H)-dependent GDHa has been disrupted by reverse genetics in P. falciparum and the effect on the antioxidant and metabolic capacities of the resulting mutant parasites was investigated. No growth defect under low and elevated oxygen tension, no up- or down-regulation of a number of antioxidant and NADP(H)-generating proteins or mRNAs and no increased levels of GSH were detected in the D10Δgdha parasite lines. Further, the fate of the carbon skeleton of [13C] labelled glutamine was assessed by metabolomic studies, revealing no differences in the labelling of α-ketoglutarate and other TCA pathway intermediates between wild type and mutant parasites. First, the data support the conclusion that D10Δgdha parasites are not experiencing enhanced oxidative stress and that GDHa function may not be the provision of NADP(H) for reductive reactions. Second, the results imply that the cytosolic, NADP(H)-dependent GDHa protein is not involved in the oxidative deamination of glutamate but that the protein may play a role in ammonia assimilation as has been described for other NADP(H)-dependent GDH from plants and fungi. The lack of an obvious phenotype in the absence of GDHa may point to a regulatory role of the protein providing glutamate (as nitrogen storage molecule) in situations where the parasites experience a limiting supply of carbon sources and, therefore, under in vitro conditions the enzyme is unlikely to be of significant importance. The data imply that the protein is not a suitable target for future drug development against intra-erythrocytic parasite development.


Spatiotemporal deep imaging of syncytium induced by the soybean cyst nematode Heterodera glycines.
Parasite infections cause dramatic anatomical and ultrastructural changes in host plants. Cyst nematodes are parasites that invade host roots and induce a specific feeding structure called a syncytium. A syncytium is a large multinucleate cell formed by cell wall dissolution-mediated cell fusion. The soybean cyst nematode (SCN), Heterodera glycines, is a major soybean pathogen. To investigate SCN infection and the syncytium structure, we established an in planta deep imaging system using a clearing solution ClearSee and two-photon excitation microscopy (2PEM). Using this system, we found that several cells were incorporated into the syncytium; the nuclei increased in size and the cell wall openings began to be visible at 2 days after inoculation (DAI). Moreover, at 14 DAI, in the syncytium developed in the cortex, there were thickened concave cell wall pillars that resembled "Parthenon pillars." In contrast, there were many thick board-like cell walls and rarely Parthenon pillars in the syncytium developed in the stele. We revealed that the syncytia were classified into two types based on the pattern of the cell wall structures, which appeared to be determined by the position of the syncytium inside roots. Our results provide new insights into the developmental process of syncytium induced by cyst nematode and a better understanding of the three-dimensional structure of the syncytium in host roots.


Substance-P is present in a subset of thyrotrophs in the human pituitary.
Substance-P immunoreactivity and tachykinin-like peptides are present in the pituitary gland of several mammalian species. In humans, however, the biochemical nature and cellular localization of pituitary substance-P has not been defined. We report here that substance-P-immunoreactive material is present in low concentrations in both the anterior and posterior lobes of the human pituitary gland. Gel chromatography and reverse phase high performance liquid chromatography indicate that the majority of the substance-P immunoreactivity in human pituitaries elutes as authentic substance-P and its oxidized derivative. Immunohistochemical studies showed substance-P-immunoreactive fibers and terminals in the posterior pituitary gland and occasional substance-P-immunoreactive cell bodies in the anterior lobe. The substance-P-immunoreactive cells were found to colocalize with a small subpopulation of TSH beta-immunoreactive cells (thyrotrophs). Substance-P immunoreactivity was also found in a pituitary microadenoma that contained numerous TSH beta-immunoreactive cells. These studies indicate that substance-P is present in the human pituitary gland, and they suggest a relationship between substance-P and thyroid function.