[Progress in prostate cancer study: 3D cell culture enables the ex vivo reproduction of tumor characteristics].
Despite new therapeutics options, Prostate Cancer (PCa) remains a public health challenge because of its high incidence and mortality. Limits in PCa research come from the lack of in vitro and in vivo models that mimic the human disease. Currently, 2D in vitro tissue culture models of PCa are widely used but they present numerous limits. They do not reproduce cellular morphology, tissue architecture, inter-patients and intratumor heterogeneity. Furthermore, they lack two key components of PCa tumors, the tumoral microenvironment and the cancer stem cells. In vivo murine models of PCa cannot be representative of all the genetic alterations known in prostate tumors and they hardly reproduce the pathophysiology of human metastatic progression. Consequently, the physiology of these in vitro and in vivo models do not well represent patients tumors. 3D cell cultures overcome many of these limits by sharing morphologic characteristics with in vivo tumors as well as reproducibility of in vitro models. 3D models of PCa include spheroids derived from tumor cell lines, and organoids, derived from patient. In 3D cell cultures, cell fitness is maintained, the physiological cells-cells and cell-matrix interactions are restored and an extracellular matrix surrounds the cells. Organoids, generated from PCa primary tumors or metastases, allow studies on cancer stem cells and their microenvironment. Moreover, organoids retain genetic integrity of PCa tumors. PCa organoid model is an innovative tool that offers great perspectives of therapeutic screening. In the future, organoids generated from patients' biopsies may also lead to personalized medicine.


Biocompatibility improvement of artificial cornea using chitosan-dextran nanoparticles containing bioactive macromolecules obtained from human amniotic membrane.
Corneal transplantation, by which the damaged cornea is replaced by a new one, suffers from limited access to HLA-compatible-donors and high maintenance and surgical costs. Therefore, artificial corneas are considered as alternative tools with promising prospects. In our previous study, a two-part-polymeric artificial cornea was composed of enhanced hydrophilic surface electrospun poly(ε-caprolactone) nanofibrous scaffold that is thermally connected to a polyvinyl alcohol-based hydrogel disk was prepared. Characterization tests revealed the prepared artificial cornea had similar biocompatible and structural characteristics regarding the natural cornea. In current study, human amniotic membrane extract containing growth factors, cytokines, anti-inflammatory factors, and anti-angiogenic factors was prepared, nano-encapsulated in chitosan-dextran nanoparticles, and physically decorated on the poly(ε-caprolactone)-polyvinyl-alcohol artificial cornea. Physicochemical and biological characterizations revealed the nano-decorated artificial cornea has more biocompatibility than the unmodified one. Our study demonstrated the bioactive macromolecules loaded on chitosan-dextran nanoparticles enhanced the anti-angiogenic property of artificial cornea through the sustained release of anti-angiogenic factors such as thrombospondin-1, endostatin, and heparin sulfate proteoglycan. Real-time-PCR and flow-cytometry assessments elucidated the vascularization was inhibited through a decrease in the expression of cluster of differentiation 31 and von-Willebrand-Factor. Our study proposed the use of biocompatible artificial cornea could be a promising strategy in corneal transplantation.


Ab initio investigation of the first hydration shell of glucose.
The interaction between sugars and water molecules plays a crucial role in exploring the complex metabolic reactions of living systems. The fully random conformational search is employed to investigate the first hydration shell structure of glucose. The circumference of glucose is divided into three hydrate sites according to the location of water molecules. Especially, four water molecules can saturate hydrate site AI and while more water molecules will be required to saturate hydrate sites AIII and AII. Moreover, the hydration energies of water molecules at different hydration region indicate that the competition of the three hydrate sites for water molecules changes dynamically with the increase of water molecules. In addition, we calculate the Raman spectra of the hydrated glucose, which are in good agreement with the experimental and theoretical Raman spectra of the glucose solution.


Mechanism of action of rab3A in mossy fiber LTP.
In mossy fiber synapses of the hippocampal CA3 region, LTP is induced by cAMP and requires the synaptic vesicle protein rab3A. In contrast, CA1-region synapses do not exhibit this type of LTP. We now show that cAMP enhances glutamate release from CA3 but not CA1 synaptosomes by (1) increasing the readily releasable pool as tested by hypertonic sucrose; (2) potentiating release evoked by KCl depolarization, which opens voltage-gated Ca2+ channels; and (3) by enhancing Ca2+ action on the secretory apparatus as monitored by the Ca2+-ionophore ionomycin. In rab3A-deficient synaptosomes, forskolin still enhances KCl- and sucrose-induced glutamate release but not ionomycin-induced release. Our results show that cAMP has multiple actions in mossy fiber synapses, of which only the direct activation of the secretory apparatus requires rab3A and functions in mfLTP.


Hemodynamic effects of innominate artery occlusive disease on anterior cerebral artery.
Stenoses of the innominate artery (IA) may affect flow conditions in the carotid arteries. However, alternating flow in ipsilateral anterior cerebral artery (ACA) due to IA stenosis is extremely rare. A 49-year-old woman who was evaluated for symptomatic cerebrovascular disease presented with right latent subclavian and right carotid system steal. Transcranial Doppler examination displayed systolic deceleration wave-forms in the right terminal internal carotid artery and alternating flow in the right ACA. Magnetic resonance angiography demonstrated tight stenosis of the right IA. For a thorough study of the hemodynamic effects of IA stenosis, a combination of duplex and transcranial Doppler examination is required.


Nematophagous fungus Pochonia chlamydosporia to control parasitic diseases in animals.
The control of gastrointestinal parasites in animals has become more challenging every year due to parasite resistance to conventional chemical control, which has been observed worldwide. Ovicidal or opportunistic fungi do not form traps to capture larvae. Their mechanism of action is based on a mechanical/enzymatic process, which enables the penetration of their hyphae into helminth eggs, with subsequent internal colonization of these. The biological control with the Pochonia chlamydosporia fungus has been very promising in the treatment of environments and prevention. When used in intermediate hosts of Schistosoma mansoni, the fungus promoted a high percentage decrease in the population density of aquatic snails. Secondary metabolites were also found in P. chlamydosporia. Many of these compounds can be used by the chemical industry in the direction of a commercial product. This review aims to provide a description of P. chlamydosporia and its possible use as a biological parasitic controller. The ovicidal fungus P. chlamydosporia is effective in the control of parasites and goes far beyond the control of verminosis, intermediate hosts, and coccidia. It can also be used not only as biological controllers in natura but also as their metabolites and molecules can have chemical action against these organisms. KEY POINTS: • The use of the fungus P. chlamydosporia is promising in the control of helminths. • Metabolites and molecules of P. chlamydosporia may have chemical action in control.


Optimal force magnitude for bodily orthodontic tooth movement with fixed appliances: A systematic review.
There is a high degree of uncertainty regarding the appropriate force level that should be applied during orthodontic tooth movement (OTM). As a result, orthodontic treatments may take longer than necessary, leading to unwanted side effects. This review aimed to identify an optimal force range with the rate of OTM as the primary outcome. External apical root resorption and pain were evaluated as secondary outcomes, and the influence of growth was examined. Five electronic databases were searched (MEDLINE [via PubMed], Embase [via OVID], Cochrane Library, CINAHL, and Web of Science) with no publication date or language restrictions. Inclusion eligibility screening, quality assessment, and data extraction were performed by 3 investigators. Each retrieved record was assessed by 2 observers independently. Only randomized controlled trials and randomized split-mouth studies were included. A total of 12 articles satisfied the inclusion criteria-two randomized controlled trials and 10 randomized split-mouth studies. Only 1 study showed a low risk of bias, whereas the remaining 11 were unclear. The qualitative analysis showed that forces between 50 cN and 250 cN produced a similar OTM rate; forces >250 cN yielded a slightly higher rate but were accompanied by adverse effects. Because of considerable heterogeneity in methodology, clinical diversity with varying forces between 18 cN and 360 cN, and poor statistical reporting, a meta-analysis was deemed inappropriate. Forces between 50 cN and 100 cN seem optimal for OTM, patient comfort and potentially exhibit fewer side effects. Nevertheless, careful data interpretation is necessary because of the lack of strong evidence. Protocol registration: PROSPERO CRD42016039985.


Endonasal endoscopic oncologic resection and reconstruction of the anterior skull base in the elderly: A single-center retrospective study.
In old and frail patients, oncologic anterior skull-base surgery through an endonasal endoscopic approach avoids the morbidity incurred by transfacial and transcranial approaches, sometimes considered unreasonable, although surgery remains the gold standard treatment for sinonasal cancer. To assess the functional and oncologic results of this surgery in over-70 year-olds. A single-center retrospective study included all patients aged over 70 years at surgery, who underwent endonasal endoscopic oncologic resection and reconstruction of the anterior skull base, between October 2008 and October 2018. Fifteen procedures in 13 patients met the inclusion criteria. Mean hospital stay was 7 days. All resections were considered R0, apart from one case with positive dura-mater margins (6.7%). All patients had complete radio-surgical treatment, in accordance with the REFCOR recommendations. Two cases of meningitis were reported (13.3%). At a median follow-up of 27 months, 4 patients presented local recurrence, 1 of whom also had lung metastases. Two patients died of disease-related or treatment-related causes. This technique is a feasible treatment in patients aged over 70 years, providing good functional results, and acceptable oncologic outcome.


Pediatric Hammertoe Recurrence-Considerations for Revision Surgical Technique and Hypoperfusion Management: A Case Report.
A 7-year-old girl presented with a recurrent hammertoe deformity causing pain with shoe wearing after a prior corrective surgery. Surgical revision required a unique approach that included a staged corrective osteotomy of the proximal phalanx because of hypoperfusion management and the application of a rotational skin flap previously described for camptodactyly correction in the hand to avoid harvesting a skin graft. Revision surgery for recurrent pediatric hammertoe deformity requires a heightened awareness of the risk for toe hypoperfusion and subsequent wound closure challenges.


Shouldn't Propranolol Be Used to Treat All Haemangiomas?
Infantile haemangioma is the most common childhood tumour. These tumours can cause significant functional and cosmetic problems. While there are many treatment modalities, propranolol is increasingly being recognised as the first-line treatment of problematic haemangiomas. This study investigates the use of oral propranolol for the treatment of all haemangiomas at a tertiary children's hospital. This is a retrospective study evaluating 15 children (3 boys and 12 girls) presenting at a tertiary children's hospital with infantile haemangioma during a 24-month period. The protocol consisted of pre-treatment ultrasonic evaluation of the lesion, followed by the commencement of propranolol therapy (2 mg/kg orally in two divided doses), with repeat imaging performed at 16-24 weeks in order to document the dimensional changes. Adverse effects of propranolol were documented. Intralesional bleomycin was utilised as a second-line modality of treatment for large or problematic haemangiomas with inadequate regression in size after oral propranolol therapy. Fifteen (15) patients with a mean age of 7 months (Range: 3-14 months) presented with haemangiomas. Ten patients presented with lesions affecting the head and neck region (67%). Three patients presented with an ulcerated haemangioma, which responded to propranolol and simple dressings and all healed completely. The average decrease in size between the ultrasonography procedures was 48.87%. Only one patient showed no improvement. No side effects were reported. Concomitant bleomycin treatment was reserved for large problematic haemangiomas and proved successful at speeding up the involution process. This study suggests that propranolol become the first-line treatment of choice for all haemangiomas. It has proven to be effective and safe for reducing the size of all haemangiomas during the proliferative phase. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Improvement of ferrous ion-dependent nitrate removal (FeNiR) process with chelating ferrous ion as substrate.
In order to improve the ferrous ion-dependent nitrate removal (FeNiR) process, hexametaphosphate chelated ferrous ion was used as substrate to replace the free ferrous ion. With hexametaphosphate chelated ferrous ion as substrate, the influent pH was adjusted to 6.8, and as a result a higher effluent pH (7.2) was detected. The volumetric removal rate (VRR) of nitrate kept at 0.42 ± 0.03 kg-N/(m3∙d) for 48 days and the corresponding nitrogen removal efficiency was 94.39 ± 4.57%. After 88 days of cultivation, FeNiR granules became small because of the oligotrophic substrate. The transmission electron microscope (TEM) analysis showed that less iron encrustation was formed on the surface or in the periplasm of FeNiR cells. The linear curve of the living cell percentage versus time showed that the death rate of FeNiR cells with chelated ferrous ion as substrate was much lower than that with free ferrous ion as substrate (0.4210 vs 0.9221). Without iron encrustation, both the FeNiR activity and alkaline phosphatase (ALP) activity of FeNiR cells kept at high level and thus the efficiency of the FeNiR reactor kept stable and high. With hexametaphosphate chelated ferrous ion as substrate, the pH in bulk liquid was high (pH = 7.2) resulting in the high FeNiR rate, and less iron encrustation was formed around cells ensuring the stability of high FeNiR rate. Therefore, using hexametaphosphate chelated ferrous ion as substrate was an efficient way to improve the FeNiR process.


Late mandibular fracture after third molar surgery: a survey of Connecticut oral and maxillofacial surgeons.
This study investigated the incidence and causative factors involved in late mandibular fractures after third molar surgery. A questionnaire was sent to 106 oral and maxillofacial surgeons in Connecticut, asking them about their experience with late fractures over a 10-year period. A 79% response indicated 28 fractures occurring in 611,000 extractions, for an incidence of 0.0046%. The cause was found to be multifactorial and included age, gender, type of impaction, preexisting infection, and failure to maintain a soft diet in the postoperative period. Most fractures occurred between the 1st and 21st days postoperatively. Three of the fractures resulted in malpractice litigation. Men over the age of 25 years should be specifically informed about the risk of late mandible fracture after third molar surgery. This group of patients should be educated about the quality and duration of a soft diet.


Gene expression analysis on small numbers of invasive cells collected by chemotaxis from primary mammary tumors of the mouse.
cDNA microarrays have the potential to identify the genes involved in invasion and metastasis. However, when used with whole tumor tissue, the results average the expression patterns of different cell types. We have combined chemotaxis-based cell collection of the invasive subpopulation of cells within the primary tumor with array-based gene expression analysis to identify the genes necessary for the process of carcinoma cell invasion. Invasive cells were collected from live primary tumors using microneedles containing chemotactic growth factors to mimic chemotactic signals thought to be present in the primary tumor. When used with mammary tumors of rats and mice, carcinoma cells and macrophages constitute the invasive cell population. Microbeads conjugated with monoclonal anti-CD11b (Mac-1alpha) antibodies were used to separate macrophages from carcinoma cells. We utilized PCR-based cDNA amplification from small number of cells and compared it to the quality and complexity of conventionally generated cDNA to determine if amplified cDNA could be used with fidelity for array analysis of this cell population. These techniques showed a very high level of correlation indicating that the PCR based amplification technique yields a cDNA population that resembles, with high fidelity, the original template population present in the small number of cells used to prepare the cDNA for use with the chip. The specific collection of invasive cells from a primary tumor and the analysis of gene expression in these cells are is now possible. By further comparing the gene expression patterns of cells collected by invasion into microneedles with that of carcinoma cells obtained from the whole primary tumor, the blood, and whole metastatic tumors, genes that contribute to the invasive process in carcinoma cells may be identified.


Nurse Work Environment and Hospital-Onset Clostridioides difficile Infection.
Clostridioides difficile is the leading cause of hospital-onset diarrhea and is associated with increased lengths of stay and mortality. While some hospitals have successfully reduced the burden of C. difficile infection (CDI), many still struggle to reduce hospital-onset CDI. Nurses-because of their close proximity to patients-are an important resource in the prevention of hospital-onset CDI. Determine whether there is an association between the nurse work environment and hospital-onset CDI. Survey data of 2016 were available from 15,982 nurses employed in 353 acute care hospitals. These data, aggregated to the hospital level, provided measures of the nurse work environments. They were merged with 2016 hospital-onset CDI data from Hospital Compare, which provided our outcome measure-whether a hospital had a standardized infection ratio (SIR) above or below the national average SIR. Hospitals above the average SIR had more infections than predicted when compared to the national average. In all, 188 hospitals (53%) had SIRs higher than the national average. The odds of hospitals having higher than average SIRs were significantly lower, with odds ratios ranging from 0.35 to 0.45, in hospitals in the highest quartile for all four nurse work environment subscales (managerial support, nurse participation in hospital governance, physician-nurse relations, and adequate staffing) than in hospitals in the lowest quartile. Findings show an association between the work environment of nurses and hospital-onset CDI. A promising strategy to lower hospital-onset CDI and other infections is a serious and sustained commitment by hospital leaders to significantly improve nurse work environments.


mTOR inhibitor PP242 increases antitumor activity of sulforaphane by blocking Akt/mTOR pathway in esophageal squamous cell carcinoma.
Sulforaphane (SFN) is a kind of isothiocyanate from cruciferous vegetables with extensive anti-tumor activity. Esophageal squamous cell carcinoma (ESCC) is a popular malignancy in East Asia, East and South Africa, while the more efficient medicines and therapeutic strategies are still lack. This study aims to explore the anti-tumor activity of SFN alone and combined with Akt/mTOR pathway inhibitors as well as the potential molecular mechanism in ESCC. Cell proliferation, migration, cell cycle phase, apoptosis and protein expression were detected with MTT assay, clone formation experiment, wound healing assays, flow cytometry and Western blot, respectively, after ESCC cells ECa109 and EC9706 treated with SFN alone or combined with Akt/mTOR inhibitors. Xenograft models were used to evaluate the efficiency and mechanism of SFN combined with PP242 in vivo. The results showed that SFN significantly inhibited the viability and induced apoptosis of ECa109 and EC9706 cells by increasing expression of Cleaved-caspase 9. SFN combined with PP242, but not MK2206 and RAD001, synergetic inhibited proliferation of ESCC cells. Moreover, compared to SFN alone, combination of SFN and PP242 had stronger inhibiting efficiency on clone formation, cell migratory, cell cycle phase and growth of xenografts, as well as the more powerful apoptosis-inducing effects on ESCC. The mechanism was that PP242 abrogated the promoting effects of SFN on p-p70S6K (Thr389) and p-Akt (Ser473) in ESCC. Our findings demonstrate that PP242 enhances the anti-tumor activity of SFN by blocking SFN-induced activation of Akt/mTOR pathway in ESCC, which provides a rationale for treating ESCC using SFN combined with Akt/mTOR pathway inhibitors.


Multiple effects of HIV-1 trans-activator protein on the pathogenesis of HIV-1 infection.
The HIV-1 trans-activator (Tat) protein is proposed as an important factor in the complex HIV-induced pathogenesis of AIDS. In this paper, multiple effects of this viral protein are described. Originally discovered as an intracellular activator of HIV-1 transcription, Tat was found to regulate viral reverse transcription as well. Trans-activator was found to be secreted by HIV-infected cells and taken up by neighbouring cells. In this way, Tat is able to affect both infected and uninfected cells. Intracellularly, Tat can deregulate the expression of several heterologous cellular and viral genes. Extracellular Tat can contribute to the spreading of HIV-1 and immunosuppression of uninfected cells. Finally, there is evidence that exogenous Tat is involved in AIDS-associated pathologies such as Kaposi's sarcoma and HIV-associated dementia. These capacities together accelerate the progression towards AIDS and make Tat an interesting candidate as a constituent of an anti-AIDS vaccine.


Highly efficient automated extraction of DNA from old and contemporary skeletal remains.
We optimised the automated extraction of DNA from old and contemporary skeletal remains using the AutoMate Express system and the PrepFiler BTA kit. 24 Contemporary and 25 old skeletal remains from WWII were analysed. For each skeleton, extraction using only 0.05 g of powder was performed according to the manufacturer's recommendations (no demineralisation - ND method). Since only 32% of full profiles were obtained from aged and 58% from contemporary casework skeletons, the extraction protocol was modified to acquire higher quality DNA and genomic DNA was obtained after full demineralisation (FD method). The nuclear DNA of the samples was quantified using the Investigator Quantiplex kit and STR typing was performed using the NGM kit to evaluate the performance of tested extraction methods. In the aged DNA samples, 64% of full profiles were obtained using the FD method. For the contemporary skeletal remains the performance of the ND method was closer to the FD method compared to the old skeletons, giving 58% of full profiles with the ND method and 71% of full profiles using the FD method. The extraction of DNA from only 0.05 g of bone or tooth powder using the AutoMate Express has proven highly successful in the recovery of DNA from old and contemporary skeletons, especially with the modified FD method. We believe that the results obtained will contribute to the possibilities of using automated devices for extracting DNA from skeletal remains, which would shorten the procedures for obtaining high-quality DNA from skeletons in forensic laboratories.


HSP 70 synthesis in clinical hyperthermia patients: preliminary results of a new technique.
Although thermotolerance may be an important variable in clinical hyperthermia, few means have been described to measure its effect or duration in the clinical setting. This study was undertaken to determine if heat shock protein 70 could be used as an assay to predict the presence of retained thermotolerance in human tumors. Tissue samples were obtained from patients undergoing hyperthermia and assayed for heat shock protein 70 synthesis. Eight patients having advanced, persistent, or recurrent malignant tumors had open-ended thermometry catheters placed into the lesion being heated. Through these catheters, tissue samples were obtained using a fine needle aspiration technique. Attempts were made to obtain samples before and after the first three heat treatments. Some samples were labeled immediately with radioactive methionine (35S) at 37 degrees C for 4-8 hr, others were given a test heat dose in vitro and then labeled. Protein synthesis profiles were analyzed by gel electrophoresis and autoradiography. Preliminary results show that it is possible to obtain tissue from hyperthermia patients in a safe and practical manner, that the rate of heat shock protein 70 synthesis can be measured in a variety of tumors, and that the persistence of thermotolerance in the clinical setting can be shown by the inability to reinduce heat shock protein 70 synthesis. The measurement of heat shock protein 70 using the described technique may provide an assay for retained thermotolerance in clinical hyperthermia. Technical difficulties which need to be addressed include obtaining sufficient tissue in all patients, confirming the presence of tumor in the obtained tissue, and obtaining tissue at more frequent intervals to best determine the kinetics of thermotolerance.


Grading of brain tumours. The British experience.
In order to ascertain how widely the Kernohan and WHO numerical grading systems for brain tumours are used in Britain and how uniformly they are applied, a questionnaire was circulated to named neuropathologists in 19 Regional Neuropathology Centres in Britain. Eighty four per cent replied within 10 days. Their replies showed considerable variation in the use of grading systems and revealed that numerical grading was required mainly by clinicians and was not necessarily favoured by pathologists. Although some advantages of a grading system were advanced, it does seem that numerical grading of brain tumours is ill-defined and controversial. Furthermore, the use of historical grading systems may inhibit the incorporation of advances in pathological investigation into the clinical management of patients with brain tumours.


Inosine Accelerates the Regeneration and Anticipates the Functional Recovery after Sciatic Nerve Crush Injury in Mice.
Trauma to the peripheral nervous system (PNS) results in loss of motor and sensory functions. After an injury, a complex series of events begins, allowing axonal regeneration and target reinnervation. However, this regenerative potential is limited by several factors such as age, distance from the lesion site to the target and severity of lesion. Many studies look for ways to overcome these limitations. Inosine, a purine nucleoside derived from adenosine, emerges as a potential treatment, due to its capacity to regulate axonal growth, neuroprotection and immunomodulation, contributing to motor recovery. However, no studies demonstrated their effects on PNS. C57/Black6 mice were submitted to sciatic nerve crush and received intraperitoneal injections of saline or inosine (70 mg/kg), one hour after injury and daily for one week. To evaluate axonal regeneration and functional recovery, electroneuromyography, Sciatic Function Index (SFI), rotarod and pinprick tests were performed. Our results showed that the inosine group presented a higher number of myelinated fibers and a large amount of fibers within the ideal G-ratio. In addition, the results of electroneuromyography showed greater amplitude of the compound muscle action potentials in the first and second weeks, suggesting anticipation of regeneration in the inosine group. We also observed in the inosine group, motor and sensory neurons survival, reduction in the number of macrophages and myelin ovoids in the sciatic nerves, and an early recovery of motor and sensory functions. Thus, we conclude that the use of inosine accelerates axonal regeneration promoting an early recovery of motor and sensory functions.


Effect of Annulation Mode of Twistarene on the Physical Property and Self-Assembly Behavior of Functionalized Curved Aromatic Molecules.
Four novel curved polycyclic aromatic hydrocarbons 3 a, 5, 8, 15 a have been synthesized and characterized, where molecules 3 a and 15 a bear [5]carbohelicene units. X-ray single crystal analyses indicate that compound 3 a shows offset packing arrangements of (P5 )- and (M5 )-isomers, and 15 a has a symmetrical plane and looks like a butterfly. In comparison, 8 exhibits a slightly curved structure, in which the significant convex-to-convex π-overlap with the shortest distance of 3.42 Å occurs. In addition, the effect of annulation mode of twistarenes on the physical properties, self-assembly behaviors, and switchable photoconductivity of the as-prepared curved aromatic compounds were further examined in a comparative manner.


Lnc-THOR silencing inhibits human glioma cell survival by activating MAGEA6-AMPK signaling.
Long non-coding RNA THOR (Lnc-THOR) binds to IGF2BP1, essential for its function. We here show that Lnc-THOR is expressed in human glioma tissues and cells. Its expression is extremely low or even undetected in normal brain tissues, as well as in human neuronal cells and astrocytes. We show that Lnc-THOR directly binds to IGF2BP1 in established and primary human glioma cells. shRNA-mediated Lnc-THOR knockdown or CRISPR/Cas9-induced Lnc-THOR knockout potently inhibited cell survival and proliferation, while provoking glioma cell apoptosis. Contrarily, forced overexpression of Lnc-THOR promoted glioma cell growth and migration. Importantly, Lnc-THOR shRNA or knockout activated MAGEA6-AMPK signaling in glioma cells. AMPK inactivation, by AMPKα1 shRNA, knockout, or dominant-negative mutation (T172A), attenuated Lnc-THOR shRNA-induced A172 glioma cell apoptosis. Moreover, CRISPR/Cas9-induced IGF2BP1 knockout activated MAGEA6-AMPK signaling as well, causing A172 glioma cell apoptosis. Significantly, Lnc-THOR shRNA was ineffective in IGF2BP1 KO A172 cells. In vivo, Lnc-THOR silencing or knockout potently inhibited subcutaneous A172 xenograft tumor growth in mice. MAGEA6 downregulation and AMPK activation were detected in Lnc-THOR-silenced/-KO A172 tumor tissues. Taken together, Lnc-THOR depletion inhibits human glioma cell survival possibly by activating MAGEA6-AMPK signaling.


Is long-lived foliage in Picea mariana an adaptation to nutrient-poor conditions?
This study evaluated the contribution of different ages of foliage to the nutrient and carbon balance of black spruce (Picea mariana (Mill.) B.S.P.) from a nutrient-poor peatland in Alberta. Seasonal patterns of foliar nitrogen and phosphorus concentration and content were examined in six needle cohorts up to 10 years old. Trees were treated to simulate excess nutrient deficiency (removal of all one-year-old foliage), nutrient excess (fertilized with 250, 50, 100 kg ha-1 NPK split application in June and July), or left as controls. Gas exchange (net assimilation-Na, stomatal conductance-gs, mesophyll conductance-gm, water-use efficiency-WUE, dark respiration-RS) was measured on six different needle cohorts in several control trees in 1989 and 1990. Nitrogen and phosphorus concentration decreased with needle age. Foliar nutrient concentration fell from April to June and then was stable until September except for the fertilized trees where it increased. There was no evidence of greater than normal retranslocation of nutrients from older needles for defoliated trees or greater than normal nutrient loading in older needles of fertilized trees. NA, gs, gm, WUE, and RS were similar for all needles up to six or eight years old, these older needles having NA of 65% of current needles and similar RS. The results do not support to conclusion that older needles of black spruce are retained as an adaptation to nutrient stress. It does not appear that older needles serve as a nutrient storage site in conditions of excess nutrient availability or a greater than normal nutrient source during times of excess nutrient deficiency. It appears that the maintenance of long-livedfoliage in black spruce does not provide for greater flexibility in tree nutrient allocation. Their contribution to the carbon balance of the tree seems to be sufficient to explain their retention.


The emotional process from diagnosis to birth following a prenatal diagnosis of fetal anomaly: A qualitative study of messages in online discussion boards.
to explore written statements found in online discussion boards where parents currently expecting, or with previous experience of expecting, a child with a prenatally diagnosed congenital anomaly communicate about their emotional process from diagnosis to birth. cross-sectional qualitative study of messages in public online discussion boards. Swedish public discussion boards about reproductive subjects. ten pregnant women and eight parents (of children with prenatal diagnoses) who had written 852 messages in five threads in Swedish online discussion boards identified via systematic searches. three phases were identified in the process of moving from the diagnosis to the birth: shock, existential crisis, and life remodeling. The people posting message ('posters') moved from initial shock to existential crisis and, lastly, a phase of remodeling life later in the pregnancy. During the pregnancy, considerable worries about both antenatal and postnatal aspects were expressed. To cope with their situation, the posters distanced themselves from the diagnoses, vented their feelings, sought control, and obtained practical support from friends and relatives. expectant parents faced with a prenatal diagnosis move from initial shock to a phase of life remodeling and acceptance. Burdened with considerable worries, expectant parents cope with their situation through informational, emotional, and instrumental support from health professionals, family, friends, and peers. health professionals should make sure that expectant parents feel involved in planning their children's postnatal care, that they are offered sufficient information, and that they have access to emotional and instrumental support structures.


Current status and future expectations of nanobodies in oncology trials.
Monoclonal antibodies have revolutionized personalized medicine for cancer in recent decades. Despite their broad application in oncology, their large size and complexity may interfere with successful tumor targeting for certain applications of cancer diagnosis and therapy. Nanobodies have unique structural and pharmacological features compared to monoclonal antibodies and have successfully been used as complementary anti-cancer diagnostic and/or therapeutic tools. Here, an overview is given of the nanobody-based diagnostics and therapeutics that have been or are currently being tested in oncological clinical trials. Furthermore, preclinical developments, which are likely to be translated into the clinic in the near future, are highlighted. Overall, the presented studies show the application potential of nanobodies in the field of oncology, making it likely that more nanobodies will be clinically approved in the upcoming future.


Economic analysis of human papillomavirus triage, repeat cytology, and immediate colposcopy in management of women with minor cytological abnormalities in Sweden.
To assess the cost-effectiveness of using human papillomavirus testing (HPV triage) in the management of women with minor cytological abnormalities in Sweden. An economic analysis based on a clinical trial, complemented with data from published meta-analyses on accuracy of HPV triage. The study takes perspective of the Swedish healthcare system. The Swedish population-based cervical cancer screening program. A decision analytic model was constructed to evaluate cost-effectiveness of HPV triage compared to repeat cytology and immediate colposcopy with biopsy, stratifying by index cytology (ASCUS = atypical squamous cells of undetermined significance, and LSIL = low-grade squamous intraepithelial lesion) and age (23-60 years, <30 years and ≥30 years). Costs, incremental cost, incremental effectiveness and incremental cost per additional high-grade lesion (CIN2+) detected. For women with ASCUS ≥30 years, HPV triage is the least costly alternative, whereas immediate colposcopy with biopsy provides the most effective option at an incremental cost-effectiveness ratio (ICER) of SEK 2,056 per additional case of CIN2+ detected. For LSIL (all age groups) and ASCUS (23-60 years and <30 years), HPV triage is dominated by immediate colposcopy and biopsy. Model results were sensitive to HPV test cost changes. With improved HPV testing techniques at lower costs, HPV triage can become a cost-effective alternative for follow-up of minor cytological abnormalities. Today, immediate colposcopy with biopsy is a cost-effective alternative compared to HPV triage and repeat cytology.


Impact of simulation-based training in addition to theoretical training versus theoretical training of nurses alone in the occurrence of adverse events related to arteriovenous fistula puncture in chronic hemodialysis patients: study for a cluster randomized controlled trial (SIMFAV2).
The technique of arteriovenous fistula (AVF) puncture is currently taught by colleagues within hemodialysis units. Even if the main principles of the technique are well known and common to all hemodialysis units, strong rationales are still missing to standardize fine practices such as the relative position of the needles, the angle of the needle at puncture, and the position of the bevel at the time of puncture and after the needle is in the vascular lumen. We are conducting a prospective, comparative, center-randomized, multicenter study involving 8 hemodialysis centers. The primary objective is to compare the number of adverse events related to AVF puncture between a group receiving theoretical training plus simulation-based training (4 centers) and a group receiving only theoretical training (4 centers). The study will include all adult patients who are scheduled to have an AVF puncture performed by a hemodialysis-trained nurse during a scheduled chronic dialysis session. We hypothesize that a training program for nurses on the AVF approach in procedural simulation versus theoretical input alone would decrease the adverse events related to AVF punctures and would be beneficial for the patient. This study is innovative for several reasons. First, simulation-based training in continuing education among professionals is not widely used. Furthermore, training allows for the standardization of practices within the team, both technically and relationally. ClinicalTrials.gov NCT05302505 . Registered on March 17, 2022.


Efficacy of dezocine on preventing opioid-induced cough during general anaesthesia induction: a PRISMA-compliant systematic review and meta-analysis.
To systematically review the effects of dezocine (DZC) on the occurrence rate and severity of opioid-induced cough (OIC). Systematic review and meta-analysis DATA SOURCES: PubMed, Embase, Cochrane Library, Ovid, Web of Science as well as Chinese BioMedical Literature & Retrieval System, China National Knowledge Infrastructure, Wanfang and VIP Data were searched from 1978 to 31 December 2020. All randomised controlled trials (RCTs) comparing DZC with placebo on the occurrence rate and severity of OIC. All data were analysed by using RevMan V.5.3. Each outcome was tested for heterogeneity, and randomised-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. Our search yielded 33 RCTs including 4442 patients, and 2521 patients were allocated into the DZC group and 1921 into the control group. Fentanyl was administrated in 1880 patients and sufentanil in 2562 patients during the induction of general anaesthesia. The meta-analysis demonstrated that DZC significantly reduced the occurrence rate of OIC induced by either fentanyl (8.8% vs 49.7%, OR=0.07, 95% CI 0.04 to 0.12, p<0.00001) or sufentanil (5.0% vs 41.5%, OR=0.07, 95% CI 0.04 to 0.12, p<0.00001). The meta-analysis also indicated that the occurrence rate of mild, moderate and severe OIC in the DZC group was remarkably lower than that of the control group (mild: 3.6% vs 13.6%, OR=0.19, 95% CI 0.14 to 0.25, p<0.00001; moderate: 2.0% vs 13.6%, OR=0.12, 95% CI 0.09 to 0.18, p<0.00001; severe: 1.0% vs 13.9%, OR=0.08, 95% CI 0.05 to 0.12, p<0.00001). Additionally, the current meta-analysis indicated that DZC pretreatment was not associated with increased occurrence rate of adverse effects (7.0% vs 4.2%, OR=2.34, 95% CI 0.60 to 9.14, p=0.22) except for dizziness (11.8% vs 0%, OR=8.06, 95% CI 1.40 to 46.35, p=0.02). This meta-analysis demonstrated that DZC significantly inhibited OIC and may be used to manage OIC. More high-quality RCTs are needed to complement the safety of DZC. CRD42019141255.


Effect of bovine lactoferrin as a novel therapeutic agent in a rat model of sepsis-induced acute lung injury.
Sepsis is a serious clinical condition resulting from severe infection. High rates of mortality and tissue damage have been reported in intensive care unit (ICU) patients with sepsis. Bovine lactoferrin (BLF) is a well-known 80-kDa glycoprotein in the transferrin family that inhibits sepsis in low-birth-weight neonates. The present study investigated the protective effects of BLF in a rat model of sepsis-induced acute lung injury (ALI). The wet/dry ratio, lipid peroxidation, antioxidant markers, total protein, total cell count, inflammatory markers and myeloperoxidase (MPO) levels were assessed. Histopathological analysis was also carried out. BLF treatment reduced the wet/dry ratio of lung tissue by 30.7% and 61.3%, and lipid peroxidation by 22.3% and 67%, at concentrations of 100 and 200 mg/kg, respectively. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (Gpx) and catalase were increased by more than 50% under treatment with 200 mg/kg BLF. Inflammatory markers, neutrophils, lymphocytes and total cell count were reduced by more than 50% under treatment with 200 mg/kg BLF. BLF treatment significantly reduced MPO activity, by 28.2% and 74.3%, at concentrations of 100 and 200 mg/kg, respectively. Neutrophilic infiltration and edema were observed in control rats. However, BLF treatment restored intestinal microvilli to the normal range and reduced inflammatory cell invasion. Collectively, these results suggest that BLF is an effective therapeutic agent against sepsis-induced ALI.


[The effect of substitution therapy on the birth weight of the newborn, its postpartum adaptation, trophic and course of the neonatal abstinence syndrome].
Evaluation of the effect of substitution therapy on the birth weight of the newborn, its postpartum adaptation and course of the neonatal abstinence syndrome. A three-year prospective study. The Department of Gynecology and Obstetrics of the Teaching Hospital and the 2nd Medical Faculty of the Charles University, Prague. This prospective study was carried out in the period of 2005-2007. Included in the study were heroin-addicted pregnant women and pregnant women who undergoing methadone and buprenorphine substitution therapy. During the 3 years we followed-up 47 heroin-addicted women and 60 women under substitution therapy for prenatal screening. Of this number, 36 pregnant women were methadone-substituted and 24 buprenorphine-substituted. Individual groups were compared using the Kruskal-Wallis ANOVA test. Correlation of dichotomic variables was evaluated by means of longlinear models. Calculations were done by means of NCSS 2002 statistical software (Number Cruncher Statistical Systems, Kaysville, UT, USA). Statistically birth weight of newborns was significantly lowest in the group of heroin-addicted women as compared to the group receiving substitution with buprenorphine p<0.01 and as compared to the group of methadone-substituted patients p<0.05. Having monitores changes in the placenta the statistically highest number of changes was exhibited by heroin users, both when compared to methadone users (p<0.01) and buprenorphine users (p<0.001). The highest statistically significant number of newborns with IUGR symptoms were born to heroin-addicted women. The lowest Apgar score was recorded in all three evaluations in the group of buprenorphine users and the highest in methadone-substituted women. Substitution therapy provides pregnant women with the possibility of social stabilization, adaptation, and adequate prenatal care. With regard to the fact that methadone substitution protracts the newborn's abstinence syndrome, attention has been recently focused on substitution with buprenorphine that seems to be a more considerate option, from this point of view.


Nickel vanadate nitrogen-doped carbon nanocomposites for high-performance supercapacitor electrode.
A nickel-vanadium-based bimetallic precursor was produced using the polymerization process by urea-formaldehyde copolymers. The precursor was then calcined at 800 °C in an argon ambiance to form a Ni3V2O8-NC magnetic nanocomposite. Powerful techniques were used to study the physical characteristics and chemical composition of the fabricated Ni3V2O8-NC electrode. PXRD, Raman, and FTIR analyses proved that the crystal structure of Ni3V2O8-NC included N-doped graphitic carbon. FESEM and TEM analyses imaging showed the distribution of the Ni3V2O8 nanoparticles on the layered graphitic carbon structure. TEM images showed the prepared sample has a particle size of around 10-15 nm with an enhanced active site area of 146 m2/g, as demonstrated by BET analysis. Ni3V2O8-NC nanocomposite exhibits magnetic behaviors and a magnetization saturation value of 35.99 emu/g. The electrochemical (EC) studies of the synthesized Ni3V2O8-NC electrode proceeded in an EC workstation of three-electrode. In a 5 M potassium hydroxide as an electrolyte, the cyclic voltmeter exhibited an enhanced capacitance (CS) of 915 F/g at 50 mV/s. Galvanic charge-discharge (GCD) study also exhibited a superior capacitive improvement of 1045 F/g at a current density (It) of 10 A/g. Moreover, the fabricated Ni3V2O8-NC nanocomposite displays a good power density (Pt) of 356.67 W/kg, improved ion accessibility, and substantial charge storage. At the high energy density (Et) of 67.34 W h/kg, the obtained Pt was 285.17 W/kg. The enhanced GCD rate, cycle stability, and Et of the Ni3V2O8-NC magnetic nanocomposite nominate the sample as an excellent supercapacitor electrode. This study paves the way for developing effective, efficient, affordable, and ecologically friendly electrode materials.


Free alpha-like material from bovine pituitaries. Removal of its O-linked oligosaccharide permits combination with lutropin-beta.
Further characterization of the free alpha subunit immunoreactive material, not combined with beta subunit in extracts of bovine pituitaries, shows that the only significant modifications, relative to alpha subunits themselves, are the oligosaccharide O-linked to threonine-43, and heterogeneity of the carboxyl terminus. Removal of the O-linked carbohydrate with a mixture of glycosidases from Streptococcus pneumoniae results in an alpha-like material capable of combining with lutropin beta subunit and, thus, the presence of the oligosaccharide is responsible for the inability of the free alpha-like material to combine with beta subunits. Amino acid compositions of tryptic peptides spanning the entire sequence indicate no change in amino acid sequence of the free alpha-like material as compared to lutropin alpha. Further, based on the similar behavior reverse phase high performance liquid chromatography of the tryptic peptides as compared to their lutropin alpha counterparts, it is concluded that no additional post-translational modifications are present. The N-linked oligosaccharides of the free alpha-like material most likely contain terminal O-sulfated N-acetylhexosamines (as do the asparagine-linked carbohydrates from the pituitary hormones) as indicated by the presence of 3 mol of sulfate/mol of free alpha-like material and the resistance of these oligosaccharides to enzymatic deglycosylation. The O-linked oligosaccharide does not contain sulfated residues.


Alternatives to toric contact lens fitting--for regular and irregular astigmatism.
Although toric contact lenses have improved in design and development and their use is increasing, further consideration should be given to the alternative methods of astigmatism correction by contact lenses. Much can still be achieved by non-toric lens, both for a wide range of astigmatism and for ease of supply. A number of these alternatives are examined, their advantages and disadvantages reappraised, and the merits of lens correction compared with surgical methods considered.


Saffron (Crocus sativus) intake provides nutritional preconditioning against myocardial ischemia-reperfusion injury in Wild Type and ApoE(-/-) mice: Involvement of Nrf2 activation.
Saffron is an antioxidant herbal derivative; however, its efficacy as a nutritional cardioprotective agent has not been fully elucidated. We investigated the cardioprotective properties of a standardized saffron aqueous extract (SFE) against ischemia/reperfusion (I/R) injury in Wild-Type (WT) and ApoE(-/-) mice and the underlying molecular mechanisms. WT and ApoE(-/-) mice were subjected to 30 min I and 2 h R, with the following per os interventions for 4 weeks: 1) WT Control Group, receiving Water for Injection (WFI); 2) WT Crocus Group, receiving SFE at a dose of 60 mg/kg/day; 3) WT Crocus + Wort group, receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus 15 min before R; 4) ApoE(-/-) Control Group, receiving WFI; 5) ApoE(-/-) Crocus Group, receiving SFE at a dose of 60 mg/kg/day and 6) ApoE(-/-) Crocus + Wort: receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus, 15 min before R. Ischemic area/area at risk (I/R%) ratio was measured. Blood samples and ischemic myocardial tissue were collected at the 10th min of reperfusion for assessment of troponin I, malondialdehyde (MDA), nitrotyrosine (NT), p-eNOS, eNOS, p-Akt, Akt, p-p42/p-p44, p-GSK3β, GSK3β, IL-6, Nrf2, HO-1 and MnSOD expression. The effect of SFE on Nrf2 expression was also evaluated in vitro. SFE reduced infarct size in WT (16.15 ± 3.7% vs 41.57 ± 2.48%, ***p < 0.001) and in ApoE(-/-) mice (16.14 ± 1.47% vs 45.57 ± 1.73%, ***p < 0.001). The administration of wortmannin resulted in partial inhibition of the infarct size limitation efficacy of SFE (in both WT and Apo-E(-/-) mice). Mice receiving SFE showed increased levels of eNOS, p-Akt, p-ERK1/2, p-44/p-42 and p-GSK3β-Ser9 and reduced expression of IL-6 and iNOS; furthermore, SFE reduced the levels of MDA and NT. SFE induced Nrf2 expression and its downstream targets, HO-1 and MnSOD in the myocardium of the treated animals, and induced Nrf2 expression in vitro in a dose-dependent manner. SFE limits myocardial infarction in Wild-Type and ApoE(-/-) mice in a multifaceted manner including activation of Akt/eNOS/ERK1/2/GSK3-β and through Nrf2 pathway, bestowing antioxidant protection against I/R.


Changes in ocular motility in Kabuki syndrome.
Kabuki syndrome is a rare genetic disorder, caused by mutation in the KMT2D or KDM6A genes, which affects several organs in the majority of patients, among which are the eyes. The most typical clinical characteristics are mental retardation, postnatal growth retardation, skeletal anomalies, and characteristic facial features. As the eyes are affected in most of the cases, ophthalmological examination is recommended for the early detection of ocular anomalies, in order to prevent visual impairment. The most frequent ocular signs are strabismus, ptosis, and refractive anomalies. A series of cases of Kabuki syndrome is described in five children, four of whom exhibited strabismus with esotropia, over action of inferior oblique muscles, and under action of superior oblique muscles associated with a V pattern. Most published papers do not report or might underestimate the ocular problems. It may be appropriate to perform orbital magnetic resonances in order to detect changes in the muscle paths that are related to the pathology of the eye movements found.


Use of venovenous extracorporeal membrane oxygenation for resection of a large paratracheal mass causing critical tracheal stenosis: A case report.
Critical airway stenosis is challenging for surgeons and anesthesiologists to secure a reliable airway for ventilation. The use of venovenous (VV)-extracorporeal membrane oxygenation (ECMO) has been described as a strategy to provide adequate gas exchange in such instances. We present a case of a young female with a complex paratracheal mass significantly compressing the trachea; a planned intraoperative VV-ECMO was instituted to allow safe orotracheal intubation of a double-lumen endotracheal tube for lung isolation and tumor resection.


Comparison between first- and second-generation test for anti-hepatitis C virus antibodies in hemodialysis patients.
The serum of 387 hemodialysis patients from 9 dialysis units was checked for anti-hepatitis C virus antibodies with a 1st-generation ELISA (Ortho) test: 61 patients were repeatedly positive. In order to avoid false-positive results, these sera were tested with a 1st-generation confirmatory RIBA test, 2nd-generation screening ELISA test and 2nd-generation confirmatory RIBA test. The 2nd-generation ELISA test confirmed data obtained with 1st-generation ELISA, however, the 1st-generation confirmatory RIBA test underestimated the number of anti-HCV-positive patients.


Monitoring clinical changes in patients with heart failure: a comparison of methods.
Although monitoring the clinical status of patients with heart failure rests at the core of clinical medicine, the ability of different techniques to reflect clinical change has not been evaluated. This study sought to describe changes in various measures of disease status associated with gradations of clinical change. A prospective, 14-center cohort of 476 outpatients was assessed at baseline and 6 +/- 2 weeks to compare changes in 7 heart failure measures with clinically observed change. Measures included health status instruments (the Kansas City Cardiomyopathy Questionnaire [KCCQ], Short Form-12, and EQ-5D), physician-assessed functional class (New York Heart Association [NYHA]), an exercise test (6-minute walk), patient weight, and a biomarker (B-type natriuretic peptide). Cardiologists, blinded to all measures except weight and NYHA, categorized clinical change ranging from large deterioration to large improvement. The KCCQ, NYHA, and 6-minute walk test were most sensitive to clinical change. For patients with large, moderate, and small deteriorations, the KCCQ decreased by 25 +/- 16, 17 +/- 14, and 5.3 +/- 11 points, respectively. For patients with small, moderate, and large improvements, the KCCQ increased by 5.7 +/- 16, 10.5 +/- 16, and 22.3 +/- 16 points, respectively (P < .01 for all compared with the no change group). New York Heart Association and 6-minute walk distance were significantly different for those with moderate and large changes (P < .05) but neither revealed a difference between those with small versus no clinical deterioration. The KCCQ had the highest c statistic for monitoring individual patients, followed by NYHA and 6-minute walk. The KCCQ, followed by the NYHA and the 6-minute walk test, most accurately reflected clinical change in patients with heart failure.


Regioselective synthesis of kojic acid esters by Bacillus subtilis protease.
The lipophilicity of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one] was improved by esterifying kojic acid with either divinyl adipate, vinyl hexanoate, vinyl octanoate or vinyl decanoate using protease from Bacillus subtilis for 7 d. 1H-NMR and 13C-NMR showed that the primary hydroxyl group at the C-7 position of kojic acid was regioselectively esterified to afford 7-O-vinyl adipoyl kojic acid, 7-O-hexanoyl kojic acid, 7-O-octanoyl kojic acid and 7-O-decanoyl kojic acid (13-27% yield). The kojic acid esters had radical scavenging activities, inhibited tyrosinase activity and was biodegradable.


Comparison of radiographic and functional results of die-punch fracture of distal radius between volar locking plating (VLP) and external fixation (EF).
The aim of this study is to investigate the radiographic and functional results of die-punch fracture of distal radius treated by volar locking plate (VLP) or external fixation (EF). Between January 2015 and June 2018, 87 patients who were treated with EF or VLP were included in this study. At postoperative 6 months and at least 12 months, radiographic and functional outcomes were evaluated, and compared between two groups using SPSS 21.0. The follow-up period was 15.6 months in average, and at the mean 8.5 weeks bony union was achieved in all patients. At 6-month visit, patients in VLP group had significantly better wrist flexion (79.2° vs. 71.8°) and pronation (79.5° vs. 75.2°) than those in EF group, but the difference was non-significant at the last visit (> 12 months); as for other parameters, no significant differences were observed. No significant difference was found between both groups in term of volar tilt, radial inclination, radial height, ulnar variance, or Gartland-Werley score and DASH. The articular step-off was significantly greater in EF than VLP group (0.6 mm vs. 0.3 mm, p < 0.001). The overall incidence of complications seemed higher in EF group (25% vs. 14%), but not approaching to the statistical significance level. Patients with VLP fixation of die-punch fractures had better wrist flexion and pronation at 6-month visit and more favorable wrist joint congruence at the last visit, but ultimately their outcome was comparable with those treated by EF.


Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.
A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames.


Filamentous morphology of bacterial pathogens: regulatory factors and control strategies.
Several studies have demonstrated that when exposed to physical, chemical, and biological stresses in the environment, many bacteria (Gram-positive and Gram-negative) change their morphology from a normal cell to a filamentous shape. The formation of filamentous morphology is one of the survival strategies against environmental stress and protection against phagocytosis or protist predators. Numerous pathogenic bacteria have shown filamentous morphologies when examined in vivo or in vitro. During infection, certain pathogenic bacteria adopt a filamentous shape inside the cell to avoid phagocytosis by immune cells. Filamentous morphology has also been seen in biofilms formed on biotic or abiotic surfaces by certain bacteria. As a result, in addition to protecting against phagocytosis by immune cells or predators, the filamentous shape aids in biofilm adhesion or colonization to biotic or abiotic surfaces. Furthermore, these filamentous morphologies of bacterial pathogens lead to antimicrobial drug resistance. Clinically, filamentous morphology has become one of the most serious challenges in treating bacterial infection. The current review went into great detail about the various factors involved in the change of filamentous morphology and the underlying mechanisms. In addition, the review discussed a control strategy for suppressing filamentous morphology in order to combat bacterial infections. Understanding the mechanism underlying the filamentous morphology induced by various environmental conditions will aid in drug development and lessen the virulence of bacterial pathogens. KEY POINTS: • The bacterial filamentation morphology is one of the survival mechanisms against several environmental stress conditions and protection from phagocytosis by host cells and protist predators. • The filamentous morphologies in bacterial pathogens contribute to enhanced biofilm formation, which develops resistance properties against antimicrobial drugs. • Filamentous morphology has become one of the major hurdles in treating bacterial infection, hence controlling strategies employed for inhibiting the filamentation morphology from combating bacterial infections.


Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene.
We have isolated a number of Drosophila cDNAs on the basis of their encoding calmodulin-binding proteins. A full-length cDNA clone corresponding to one of these genes has been cloned and sequenced. Conservation of amino acid sequence and tissue-specific expression are observed between this gene and the transient receptor potential (trp) gene. We propose the name transient receptor potential-like (trpl) to describe this newly isolated gene. The trpl protein contains two possible calmodulin-binding sites, six transmembrane regions, and a sequence homologous to an ankyrin-like repeat. Structurally, the trpl and trp proteins resemble cation channel proteins, particularly the brain isoform of the voltage-sensitive Ca2+ channel. The identification of a protein similar to the trp gene product, yet also able to bind Ca2+/calmodulin, allows for a reinterpretation of the phenotype of the trp mutations and suggests that both genes may encode light-sensitive ion channels.


An investigation into the short-term effects of clomipramine (Anafranil) administered in low doses, on weight.
Patients treated with four dosage regimes of clomipramine (Anafranil) 10 mg t.d.s., 30 mg o.n., 25 mg t.d.s. and 75 mg o.n. in a clinical trial lasting four weeks were regularly weighed. Due allowance was made for the normality or otherwise of normal weight, appetite and, in women, menstruation. There was no evidence that during the four weeks of this particular study and on these doses of clomipramine patients showed any increase in weight.


Absorption kinetics of oral and rectal flecainide in healthy subjects.
The absorption kinetics of different pharmaceutical formulations of orally and rectally administered flecainide have been assessed in a cross-over study in 7 healthy volunteers. The subjects received single doses of flecainide after a washout period of at least one week. A tablet, an oral solution, a rectal solution and a 10 min i.v. infusion during 10 min each containing 100 mg flecainide were administered to the subjects in a randomized order. The mean absolute bioavailability was 98%, 78% and 81% for the rectal and oral solutions and the tablet. The lag time after administration of the oral solution was 0.33 h and it was 0.86 h after the tablet and 0.18 h after the rectal solution. The mean time to the peak serum concentration (tmax) after the rectal solution (0.67 h) was shorter than after either the tablet (4 h) or oral solution (1 h). The maximum serum concentration (Cmax) was 0.29 mg.l-1 after the rectal solution, 0.14 mg.l-1 after the tablet and 0.17 mg.l-1 after the oral solution. All the volunteers showed significantly higher serum flecainide concentrations during the first 20 min of the absorption phase after rectal administration of 100 mg flecainide as a solution compared to its oral administration. based on the absolute bioavailability, Cmax, tmax, and lag times, rectal administration of flecainide solution gave a better absorption profile than after oral tablet or solution.


Embryonic and postnatal development of masticatory and tongue muscles.
This review summarizes findings concerning the unique developmental characteristics of mouse head muscles (mainly the masticatory and tongue muscles) and compares their characteristics with those of other muscles. The developmental origin of the masticatory muscles is the somitomeres, whereas the tongue and other muscles, such as the trunk (deep muscles of the back, body wall muscles) and limb muscles, originate from the somites. The program controlling the early stages of masticatory myogenesis, such as the specification and migration of muscle progenitor cells, is distinctly different from those in trunk and limb myogenesis. Tongue myogenesis follows a similar regulatory program to that for limb myogenesis. Myogenesis and synaptogenesis in the masticatory muscles are delayed in comparison with other muscles and are not complete even at birth, whereas the development of tongue muscles proceeds faster than those of other muscles and ends at around birth. The regulatory programs for masticatory and tongue myogenesis seem to depend on the developmental origins of the muscles, i.e., the origin being either a somite or somitomere, whereas myogenesis and synaptogenesis seem to progress to serve the functional requirements of the masticatory and tongue muscles.


MicroRNAs as biomarkers for early diagnosis, targeting and prognosis of prostate cancer.
Globally, prostate cancer (PC) is leading cause of cancer-related mortality in men worldwide. Despite significant advances in the treatment and management of this disease, the cure rates for PC remains low, largely due to late detection. PC detection is mostly reliant on prostate-specific antigen (PSA) and digital rectal examination (DRE); however, due to the low positive predictive value of current diagnostics, there is an urgent need to identify new accurate biomarkers. Recent studies support the biological role of microRNAs (miRNAs) in the initiation and progression of PC, as well as their potential as novel biomarkers for patients' diagnosis, prognosis, and disease relapse. In the advanced stages, cancer-cell-derived small extracellular vesicles (SEVs) may constitute a significant part of circulating vesicles and cause detectable changes in the plasma vesicular miRNA profile. Recent computational model for the identification of miRNA biomarkers discussed. In addition, accumulating evidence indicates that miRNAs can be utilized to target PC cells. In this article, the current understanding of the role of microRNAs and exosomes in the pathogenesis and their significance in PC prognosis, early diagnosis, chemoresistance, and treatment are reviewed.


Genome-wide identification and analysis of the aldehyde dehydrogenase (ALDH) gene superfamily in apple (Malus × domestica Borkh.).
Aldehyde dehydrogenases (ALDHs) represent a protein superfamily encoding NAD(P)(+)-dependent enzymes that oxidize a wide range of endogenous and exogenous aliphatic and aromatic aldehydes. In plants, they are involved in many biological processes and play a role in the response to environmental stress. In this study, a total of 39 ALDH genes from ten families were identified in the apple (Malus × domestica Borkh.) genome. Synteny analysis of the apple ALDH (MdALDH) genes indicated that segmental and tandem duplications, as well as whole genome duplications, have likely contributed to the expansion and evolution of these gene families in apple. Moreover, synteny analysis between apple and Arabidopsis demonstrated that several MdALDH genes were found in the corresponding syntenic blocks of Arabidopsis, suggesting that these genes appeared before the divergence of lineages that led to apple and Arabidopsis. In addition, phylogenetic analysis, as well as comparisons of exon-intron and protein structures, provided further insight into both their evolutionary relationships and their putative functions. Tissue-specific expression analysis of the MdALDH genes demonstrated diverse spatiotemporal expression patterns, while their expression profiles under abiotic stress and various hormone treatments indicated that many MdALDH genes were responsive to high salinity and drought, as well as different plant hormones. This genome-wide identification, as well as characterization of evolutionary relationships and expression profiles, of the apple MdALDH genes will not only be useful for the further analysis of ALDH genes and their roles in stress response, but may also aid in the future improvement of apple stress tolerance.


Isolation and absolute configuration of new bioactive marine steroids from Euryspongia n. sp.
The apolar fraction of the crude alcoholic extract of the sponge Euryspongia n. sp. was shown to display anti-inflammatory activity. Bioassay guided chromatographic purification led to the isolation of a known compound petrosterol (1) of 3beta-hydroxy-24-norchol-5-en-23-oic acid (2), which has never yet been found as a natural substance, and of a new steroid, 3beta-hydroxy-26-norcampest-5-en-25-oic acid (3). The absolute configurations of 2 and 3 were deduced from comparative 1H NMR data of the (S)- and (R)-phenylglycine methyl ester derivatives. These compounds were evaluated for their anti-inflammatory activity against 6-keto-prostaglandinF1alpha release in a human keratinocyte cell line HaCaT.


Multiple coronary artery aneurysms with aortic sinus aneurysms. A case report.
Aneurysms of the right main, left anterior descending, and left circumflex coronary arteries occurred with aneurysms of all three aortic sinuses in a 44-year-old woman. There was also moderate blood eosinophilia. Necropsy revealed severe chronic inflammation and fibrosis of the arterial and sinus aneurysms, but no evidence of generalized vasculitis.


A WNTer revisit: new faces of β-catenin and TCFs in pluripotency.
New evidence has revealed interesting aspects of how the Wnt-β-catenin pathway controls self-renewal and lineage differentiation of pluripotent embryonic stem cells. Although Wnt-β-catenin signaling is dispensable for the self-renewal of naive mouse embryonic stem cells, it facilitates their expansion and resistance to differentiation through an unconventional dual mechanism involving the transcriptional repressor T cell factor (TCF) 3 and the transcriptional activator TCF1.


Moderate zinc and vitamin A deficiency in breast milk of mothers from East-Jakarta.
To gain information about the micronutrient status of urban, middle-income, breast-feeding mothers in relation to zinc and selected fat-soluble vitamins in plasma and breast milk and to assess possible interaction between the measured micronutrients. Cross-sectional study. 91 mothers and their infants living in middle-income areas of Jakarta, Indonesia. None of the measured anthropometric data of the mothers (e.g. BMI: 22.0+/-3.1 kg/m2) and their infants (birth weight: 3.2+/-0.5 kg) gave any indication of undernutrition. The mean concentrations in blood were 124+/-18 g/l for hemoglobin, 385+/-111 microg/l for retinol, 34+/-23 microg/l for alpha-carotene, 104+/-72 microg/l for beta-carotene, 7.7+/-3.3 mg/l for alpha-tocopherol, 0.57+/-0.23 mg/l for gamma-tocopherol, 855+/-242 microg/l for zinc, and the median concentration of lycopene was 29 microg/l. The median breast milk concentrations were 420 microg/l for retinol, 7.8 microg/l for beta-carotene, and 2.7 mg/l for zinc. With increased duration of lactation, vitamin A and zinc concentrations significantly decreased in breast milk whereas plasma zinc concentration increased. Plasma alpha- and beta-carotene were positively correlated (P < 0.0001) with each other and with plasma lycopene. Breast milk beta-carotene was positively correlated with breast milk retinol and with plasma beta-carotene (P < 0.0001). There was no correlation between zinc and vitamin A in either breast milk or plasma. Forty per cent of the mothers were anemic, 29.1% had a low plasma zinc concentration, and 23.7% had a moderately low plasma vitamin A concentration. Breast milk from 70% of the women had a low concentration of vitamin A and that from 66% had a low concentration of zinc. Multi-micronutrient intervention should be considered to provide a sufficient supply of zinc and vitamin A for growth of exclusively breast-fed infants.


Relationship between HLA molecules and late restenosis after coronary stent placement.
The objective of this study is to confirm whether there is relation between the human leucocyte antigen (HLA) locus and restenosis after percutaneous coronary intervention (PCI) holds in our patient population and whether it can be useful as a prognostic factor. We examined the HLA phenotypes in 46 consecutive patients (39 men, 7 women, mean age of 57 ± 9 years) who had successful stent implantation in the coronary artery. Selective coronary arteriography was performed 6 months after coronary stenting to assess the presence of restenosis. The HLA phenotyping was performed for HLA-A,-B,-C antigens by Terasaki microlymphocytotoxicity technique and for HLA-DR alleles with PCR-SSP technique. Restenosis(R+) was present in 12 (26.1%) patients (11 men, 1 woman, mean age of 57 ± 10 years). For HLA Class I antigens frequency of HLA-B62 and HLA-CW2 antigen was slightly higher in restenotic patients but did not reach statistical significance. For HLA-DR alleles restenotic patients had higher frequencies for HLA-DRB1(∗)01(R+ %25, R- %14.7), and HLA-DR11(R+ %41.7, R- %20.6), without reaching statistical significance and lower frequencies for DR7(R+ %0, R- %17.6) and D13(R+%8.3, R- %32.4) and HLA-DR53 (R+ %25, R- %35.3) without reaching statistical significance. In conclusion, results show that there was no relationship between the development of restenosis and HLA-subtypes.


A method for evaluation of conduction anesthesia.
We propose a new method for evaluation of conduction anesthesia in animals: by the degree of prolongation of cardiac cycle during vagus nerve stimulation by solitary electric discharges synchronous to the dominant ECG wave, proximally from the site of anesthetic application on the nerve.


Development of adiposity, obesity and age at menarche: an 8-year follow-up study in Portuguese schoolgirls.
It has been suggested that the decline in menarcheal age is associated with the increase of obesity prevalence. To examine the association between age at menarche and adiposity development from age 7 to 15 years. A cohort of 109 schoolgirls from Viana do Castelo (Northern Portugal). Anthropometric measurements (height, weight, and triceps and subscapular skinfold thicknesses) were longitudinally obtained at 7, 8, 9, and 15 years. Waist circumference and self-reported age at menarche were obtained at age 15. Obesity was defined by the cut-off value of 30% body fat. Ages of <12 years, 12-13 years, and >13 years were classified as early menarche (EM), average menarche (AM) and late menarche (LM), respectively. Median menarcheal age was 12.0 years (range, 8-15 years), with 26.6% of girls classified as EM. Compared with their LM peers, EM girls were always fatter (p=0.001) and had higher waist circumference at age 15 (p=0.009). All variables showed significant negative associations with age at menarche, except subscapular to triceps skinfold ratio at all ages and height at age 15. At both ages 9 and 15 years, LM girls had the lowest prevalence of obesity (4.5% and 9.1%, respectively). The 8-year incidence of obesity in EM girls was 24.1%, while that in the AM plus LM group was 13.8% (p=0.005). EM seems to be a risk factor for the development of obesity during adolescence. However, this vulnerability may start to be programmed before menarche as girls with precocious menarche were already fatter than their late-maturing peers at age 7 years.


Isolation and characterization of horny cell membrane.
The cornified cell membrane and thickened marginal band were obtained from human stratum corneum by a new, faster procedure involving extraction, tripsinization, and density gradient centrifugation. Observations revealed a fine membranous structure with a thickened inner surface of approximately 150 A (marginal band). Each of the membranous samples contained a level of half-cystines markedly higher in amount than that of earlier findings by Matotsy and Matotsy [5]. The samples also contained high amounts of glutamic acid and lysine residues many of which constitute the epsilon-(gamma-glutamyl) lysine cross-linkages of the cell membrane. This study presents the simple isolation procedure and its results highlight the high content of half-cystines in the basic membrane fraction. In addition, the study reveals the importance of S-S cross-linkages during the formation of the cell membrane.


A new Anopheles (Dipt., Culicidae) from Nigeria together with a note on An. brohieri Edwards.
A new Anopheles species of the subgenus Cellia Theobald, named An. cristipalpis, is described from five females caught in human bait catches in Nigeria. A description is also given of three females that are apparently an atypical form of An. brohieri Edwards.


Miscibility-Controlled Phase Separation in Double-Cable Conjugated Polymers for Single-Component Organic Solar Cells with Efficiencies over 8 .
A record power conversion efficiency of 8.40 % was obtained in single-component organic solar cells (SCOSCs) based on double-cable conjugated polymers. This is realized based on exciton separation playing the same role as charge transport in SCOSCs. Two double-cable conjugated polymers were designed with almost identical conjugated backbones and electron-withdrawing side units, but extra Cl atoms had different positions on the conjugated backbones. When Cl atoms were positioned at the main chains, the polymer formed the twist backbones, enabling better miscibility with the naphthalene diimide side units. This improves the interface contact between conjugated backbones and side units, resulting in efficient conversion of excitons into free charges. These findings reveal the importance of charge generation process in SCOSCs and suggest a strategy to improve this process: controlling miscibility between conjugated backbones and aromatic side units in double-cable conjugated polymers.


Protein-level mutant p53 reporters identify druggable rare precancerous clones in noncancerous tissues.
Detecting and targeting precancerous cells in noncancerous tissues is a major challenge for cancer prevention. Massive stabilization of mutant p53 (mutp53) proteins is a cancer-specific event that could potentially mark precancerous cells, yet in vivo protein-level mutp53 reporters are lacking. Here we developed two transgenic protein-level mutp53 reporters, p53R172H-Akaluc and p53-mCherry, that faithfully mimic the dynamics and function of mutp53 proteins in vivo. Using these reporters, we identified and traced rare precancerous clones in deep noncancerous tissues in various cancer models. In classic mutp53-driven thymic lymphoma models, we found that precancerous clones exhibit broad chromosome number variations, upregulate precancerous stage-specific genes such as Ybx3 and enhance amino acid transport and metabolism. Inhibiting amino acid transporters downstream of Ybx3 at the early but not late stage effectively suppresses tumorigenesis and prolongs survival. Together, these protein-level mutp53 reporters reveal undercharacterized features and vulnerabilities of precancerous cells during early tumorigenesis, paving the way for precision cancer prevention.


Tailoring diamondised nanocarbon-loaded poly(lactic acid) composites for highly electroactive surfaces: extrusion and characterisation of filaments for improved 3D-printed surfaces.
A new 3D-printable composite has been developed dedicated to electroanalytical applications. Two types of diamondised nanocarbons - detonation nanodiamonds (DNDs) and boron-doped carbon nanowalls (BCNWs) - were added as fillers in poly(lactic acid) (PLA)-based composites to extrude 3D filaments. Carbon black served as a primary filler to reach high composite conductivity at low diamondised nanocarbon concentrations (0.01 to 0.2 S/cm, depending on the type and amount of filler). The aim was to thoroughly describe and understand the interactions between the composite components and how they affect the rheological, mechanical and thermal properties, and electrochemical characteristics of filaments and material extrusion printouts. The electrocatalytic properties of composite-based electrodes, fabricated with a simple 3D pen, were evaluated using multiple electrochemical techniques (cyclic and differential pulse voltammetry and electrochemical impedance spectroscopy). The results showed that the addition of 5 wt% of any of the diamond-rich nanocarbons fillers significantly enhanced the redox process kinetics, leading to lower redox activation overpotentials compared with carbon black-loaded PLA. The detection of dopamine was successfully achieved through fabricated composite electrodes, exhibiting lower limits of detection (0.12 μM for DND and 0.18 μM for BCNW) compared with the reference CB-PLA electrodes (0.48 μM). The thermogravimetric results demonstrated that both DND and BCNW powders can accelerate thermal degradation. The presence of diamondised nanocarbons, regardless of their type, resulted in a decrease in the decomposition temperature of the composite. The study provides insight into the interactions between composite components and their impact on the electrochemical properties of 3D-printed surfaces, suggesting electroanalytic potential.


Angiomatoid fibrous histiocytoma on the hard palate: case report.
Angiomatoid fibrous histiocytoma (AFH) is a rare, soft tissue sarcoma, which is slow growing with low metastatic potential. We recently had a patient present with AFH, which had a palatal perforation and it looked like a cyst in the occlusal view. Therefore, the radiological and histological features of AFH are reported herein. In addition, the differential diagnosis for this lesion is also discussed with a review of the literature. A 23-year-old woman presented with a spontaneous perforation of the palate. Clinically, a painless and ulcerative lesion was shown on the mid-palate area. Radiological findings revealed a well-demarcated, homogeneous, oval-shaped radiolucent lesion in the occlusal view. Histological examination with incisional biopsy, showed a relatively well-defined cystic-like mass including tumor cells. Taking into consideration the histological and immunohistochemical findings, the presented lesion was diagnosed as AFH. Under general anesthesia, the patient underwent a modified cylindrical partial maxillectomy including safety margins. In the present case, clinically differential diagnosis can be made with various diseases that have palatal perforations such as trauma, infection, neoplasia, collagen vascular disease, and idiopathic conditions. The treatment recommended in the literature has been radial excision. The prognosis of the tumor has been favorable.


Factors Affecting Anxiety and Depression in Caregivers of Hemodialysis Patients.
Anxiety and depression have high levels in caregivers of patients on hemodialysis and are strongly associated with demographic factors. The aim of this study was to evaluate the factors affecting anxiety and depression in caregivers of hemodialysis patients. Four hundred and fourteen (414) caregivers (98 males and 316 females) participated in this study. Depression and anxiety were assessed by the Hospital Anxiety and Depression Scale (HADS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). Multinomial logistic regression was performed to estimate the factors being independently associated with anxiety and depression levels. Multiple linear regression was performed to estimate the factors being independently associated with Beck Depression Inventory and State-Trait Anxiety Inventory. From a total of 414 participants, 125 (30.2%) had depression and 215 (52%) had anxiety. The median age of respondents was 54.34 (43.9-66.28) years, with half of the sample's age ranging from 43.9 to 66.28 (IQR). Depression and anxiety were significantly associated with parents or siblings, low level of education, increased caregivers' age, retirement, poor financial condition, having children, and comorbidities. In this study, a significant proportion of caregivers were found to have high levels of depression and anxiety. Thus, a formal screening can contribute to early diagnosis and treatment of depression and anxiety in caregivers of patients on hemodialysis.


Replacement of the hepatitis E virus ORF3 protein PxxP motif with heterologous late domain motifs affects virus release via interaction with TSG101.
The ORF3 protein of hepatitis E virus (HEV) contains a "PSAP" amino acid late domain motif, which allows for interaction with the endosomal sorting complexes required for transport (ESCRT) pathway aiding virion release. Late domain motifs are interchangeable with other viral late domain motifs in several enveloped viruses, however, it remains unknown whether HEV shares this functional interchangeability and what implications this might have on viral replication. In this study, by substituting heterologous late domain motifs (PPPY, YPDL, and PSAA) for the HEV ORF3 late domain (PSAP), we demonstrated that deviation from the PSAP motif reduces virus release as measured by viral RNA in culture media. Virus release could not be restored by insertion of a heterologous late domain motif or by supplying wild-type ORF3 in trans, suggesting that the HEV PSAP motif is required for viral exit which cannot be bypassed by the use of alternative heterologous late domains.


Endovascular Reconstruction of Aortoiliac Occlusive Disease with an Aberrant Pelvic Kidney.
Aortoiliac occlusive disease coincident with a congenital ectopic pelvic kidney is a rare occurrence. Traditionally, the treatment has been open aortobifemoral repair with reimplantation of the renal artery. We present a patient with Trans-Atlantic Inter-Society Consensus (TASC) D bilateral aortoiliac occlusive disease, an ectopic pelvic kidney, and prohibitive medical comorbidities. We describe a totally endovascular repair using a chronic total occlusion crossing device, a luminal re-entry device, and balloon-mounted covered stents to revascularize the lower extremities and the ectopic pelvic kidney. We discuss various aspects of this endovascular approach as the incidence of patients with TASC D lesions and prohibitive comorbidities continue to rise.


Associations Between Rurality, pre-pregnancy Health Status, and Macrosomia in American Indian/Alaska Native Populations.
To examine the relationships between pre-pregnancy diabetes mellitus (DM), gestational diabetes mellitus (GDM), pre-pregnancy body mass index (BMI) and county-level social determinants of health, with infant macrosomia within a sample of American Indian/Alaska Native (AI/AN) women receiving Indian Health Service (IHS) care. The sample included women-infant dyads representing 1,136 singleton births from fiscal year 2011 (10/1/2019-9/30/2011). Data stemmed from the IHS Improving Health Care Delivery Data Project. Multivariate generalized linear mixed models were fitted to assess the association of macrosomia with pre-pregnancy health status and social determinants of health. Nearly half of the women in the sample were under age 25 years (48.6%), and most had Medicaid health insurance coverage (76.7%). Of those with a pre-pregnancy BMI measure, 66.2% were overweight or obese. Although few women had pre-pregnancy DM (4.0%), GDM was present in 12.8% of women. Most women had a normal term delivery (85.4%). Overweight, obesity, pre-pregnancy DM, and county-level rurality were all significantly associated with higher odds of infant macrosomia.


Relationship of Myocardial Strain and Markers of Myocardial Injury to Predict Segmental Recovery After Acute ST-Segment-Elevation Myocardial Infarction.
Late gadolinium-enhanced cardiovascular magnetic resonance imaging overestimates infarct size and underestimates recovery of dysfunctional segments acutely post ST-segment-elevation myocardial infarction. We assessed whether cardiovascular magnetic resonance imaging-derived segmental myocardial strain and markers of myocardial injury could improve the accuracy of late gadolinium-enhancement in predicting functional recovery after ST-segment-elevation myocardial infarction. A total of 164 ST-segment-elevation myocardial infarction patients underwent acute (median 3 days) and follow-up (median 9.4 months) cardiovascular magnetic resonance imaging. Wall-motion scoring, feature tracking-derived circumferential strain (Ecc), segmental area of late gadolinium-enhancement (SEE), microvascular obstruction, intramyocardial hemorrhage, and salvage index (MSI) were assessed in 2624 segments. We used logistic regression analysis to identify markers that predict segmental recovery. At acute CMR 32% of segments were dysfunctional, and at follow-up CMR 19% were dysfunctional. Segmental function at acute imaging and odds ratio (OR) for functional recovery decreased with increasing SEE, although 33% of dysfunctional segments with SEE 76% to 100% improved. SEE was a strong predictor of functional improvement and normalization (area under the curve [AUC], 0.840 [95% confidence interval {CI}, 0.814-0.867]; OR, 0.97 [95% CI, 0.97-0.98] per +1% SEE for improvement and AUC, 0.887 [95% CI, 0.865-0.909]; OR, 0.95 [95% CI, 0.94-0.96] per +1% SEE for normalization). Its predictive accuracy for improvement, as assessed by areas under the receiver operator curves, was similar to that of MSI (AUC, 0.840 [95% CI, 0.809-0.872]; OR, 1.03 [95% CI, 1.02-1.03] per +1% MSI for improvement and AUC, 0.862 [0.832-0.891]; OR, 1.04 [95% CI, 1.03-1.04] per +1% SEE for normalization) and Ecc (AUC, 0.834 [95% CI, 0.807-0.862]; OR, 1.05 [95% CI, 1.03-1.07] per +1% MSI for improvement and AUC, 0.844 [95% CI, 0.818-0.871]; OR, 1.07 [95% CI, 1.05-1.10] per +1% SEE for normalization), and for normalization was greater than the other predictors. MSI and Ecc remained as significant after adjustment for SEE but provided no significant increase in predictive accuracy for improvement and normalization compared with SEE alone. MSI had similar predictive accuracy to SEE for functional recovery but was not assessable in 25% of patients. Microvascular obstruction provided no incremental predictive accuracy above SEE. This multicenter study confirms that SEE is a strong predictor of functional improvement post ST-segment-elevation myocardial infarction, but recovery occurs in a substantial proportion of dysfunctional segments with SEE >75%. Feature tracking-derived Ecc and MSI provide minimal incremental benefit to SEE in predicting segmental recovery. URL: http://www.isrctn.com. Unique identifier: ISRCTN70913605.


Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior.
HAP-1 is a huntingtin-associated protein that is enriched in the brain. To gain insight into the normal physiological role of HAP-1, mice were generated with homozygous disruption at the Hap1 locus. Loss of HAP-1 expression did not alter the gross brain expression levels of its interacting partners, huntingtin and p150glued. Newborn Hap1(-/-) animals are observed at the expected Mendelian frequency suggesting a non-essential role of HAP-1 during embryogenesis. Postnatally, Hap1(-/-) pups show decreased feeding behavior that ultimately leads to malnutrition, dehydration and premature death. Seventy percent of Hap1(-/-) pups fail to survive past the second postnatal day (P2) and 100% of Hap1(-/-) pups fail to survive past P9. From P2 until death, Hap1(-/-) pups show markedly decreased amounts of ingested milk. Hap1(-/-) pups that survive to P8 show signs of starvation including greatly decreased serum leptin levels, decreased brain weight and atrophy of the brain cortical mantel. HAP-1 is particularly enriched in the hypothalamus, which is well documented to regulate feeding behavior. Our results demonstrate that HAP-1 plays an essential role in regulating postnatal feeding.


Analysis of detomidine in horse blood, plasma and urine samples utilizing a sensitive gas chromatography-mass spectrometry method.
Chemical ionization- and electron impact ionization-selective ion monitoring provided a simple and sensitive method for measuring detomidine (Domosedan), a potent sedative-analgesic drug for horses and cattle. Chemical ionization was at least 10 times more sensitive than electron impact ionization. By using propranolol as an internal standard, we found that the recovery of detomidine from the extraction procedure used in this study was greater than 75% for plasma, whole blood, or urine samples. Approximately 68% of detomidine was bound to plasma protein and 53% was bound to red blood cells.


Effect of n-alcohols and glycerol on the pretransition of dipalmitoylphosphatidylcholine.
We have systematically investigated the effect of short-chain n-alcohols and glycerol on the pretransition of 1,2-dipalmitoylphosphatidylcholine (DPPC) by spectrophotometry. It is found that the n-alcohols and glycerol remove the pretransition above a critical concentration for each ligand. In addition, the short-chain n-alcohols below the critical concentration decrease the pretransition temperature. The longer the aliphatic chain length of the n-alcohol (up to butanol) the greater the decrease in the pretransition temperature, and the lower the concentration necessary to remove the pretransition. However, glycerol differs from the short-chain n-alcohols in that it has no significant effect on either the pretransition or the main transition, but it is also capable of removing the pretransition above a critical concentration. It has previously been shown that alcohols have a biphasic effect on the main transition temperature of phosphatidylcholines (Rowe, E.S. (1983) Biochemistry 22, 3299-3305). At high alcohol concentrations, the main transition is not thermodynamically reversible (Rowe, E.S. (1985) Biochim. Biophys. Acta 813, 321-330). Recently, Simon and McIntosh (Biochim. Biophys. Acta (1984) 773, 169-172) have identified that at high ethanol concentration DPPC exists in the interdigitated phase. The critical ligand concentration at which the pretransition disappears coincides with the induction of main transition hysteresis and the biphasic alcohol effect in the main transition. These three effects appear to correlate with the induction of the interdigitated gel state by alcohols and glycerol.


Histogram analysis of diffusion kurtosis imaging estimates for in vivo assessment of 2016 WHO glioma grades: A cross-sectional observational study.
To assess the diagnostic performance of histogram analysis of diffusion kurtosis imaging (DKI) maps for in vivo assessment of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) integrated glioma grades. Seventy-seven patients with histopathologically-confirmed glioma who provided written informed consent were retrospectively assessed between 01/2014 and 03/2017 from a prospective trial approved by the local institutional review board. Ten histogram parameters of mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were independently assessed by two blinded physicians from a volume of interest around the entire solid tumor. One-way ANOVA was used to compare MK and MD histogram parameter values between 2016 CNS WHO-based tumor grades. Receiver operating characteristic analysis was performed on MK and MD histogram parameters for significant results. The 25th, 50th, 75th, and 90th percentiles of MK and average MK showed significant differences between IDH1/2wild-type gliomas, IDH1/2mutated gliomas, and oligodendrogliomas with chromosome 1p/19q loss of heterozygosity and IDH1/2mutation (p<0.001). The 50th, 75th, and 90th percentiles showed a slightly higher diagnostic performance (area under the curve (AUC) range; 0.868-0.991) than average MK (AUC range; 0.855-0.988) in classifying glioma according to the integrated approach of 2016 CNS WHO. Histogram analysis of DKI can stratify gliomas according to the integrated approach of 2016 CNS WHO. The 50th (median), 75th, and the 90th percentiles showed the highest diagnostic performance. However, the average MK is also robust and feasible in routine clinical practice.