Vertebral compression fractures managed with brace: risk factors for progression.
The aim of this study is to identify risk factors for vertebral compression fracture (VCF) progression in patients treated conservatively with a brace. Then, a case-control study was designed. All patients over 50 years old with diagnosis of thoracic or lumbar VCF (T5 to L5) in absence of underlying oncological process, treated conservatively with brace, and consecutively attended at our department from January 2017 to June 2021 were retrospectively selected for analysis. Patients missed for follow-up or dead during the first 3 months of follow-up were excluded. Five hundred and eighty-two consecutive patients were recorded. Incomplete follow-up excluded 74 patients and other 19 died in the first three months after diagnosis, so 489 cases were finally analyzed. Median follow-up was 21 (IQR 13;30) weeks. Increased collapse of the vertebral body was found in 29.9% of VCFs with a median time to progression of 9 (IQR 7;13) weeks. Male gender (OR 1.6), type A3 fracture of the AOSpine classification (OR 2.7), thoracolumbar junction location (OR 1.7), and incorrect use of the brace (OR 3.5) were identified as independent risk factors for progression after multivariable analysis. Male gender, type A3 fracture of the AOSpine classification, thoracolumbar junction location, and incorrect use of the brace were identified as independent risk factors for VCF progression, which resulted in worse pain control, when treated with brace. Thus, other treatments such as percutaneous vertebral augmentation could be considered to avoid progression in selected cases, since collapse rate has been demonstrated lower with these procedures.


[Pediatric intervertebral disc calcification: A rare cause of acquired torticollis. Case report].
Pain and cervical muscle spasm are common reasons why parents bring children to the pediatric emergency department. The first steps are the gathering of medical history of the patient and a physical examination. If musculoskeletal damage is suspected, cervical spine x-rays should be obtained. An intervertebral disc calcification finding, in the absence of other radiological lesions should suggest pediatric intervertebral disc calcification. To present a case of intervertebral disc calcification, a rare condition that must be considered in the differential diagnosis of torticollis and neck pain in childhood. A seven-year-old male patient without morbid history and no history of trauma or rough sport practice. He consulted the emergency room for pain and cervical contracture for the last six days. C reactive protein and red cell sedimentatio rates were slightly elevated. Imaging studies showed calcification of the C5-C6 intrvertebral disc and anterior disc protrusion. The patient was hospitalized for evaluation and pain management, with good clinical response and continue afterwards with non-steroidal anti-inflammatory drugs and a soft collar. At the 6-month-follow up, the patient had resolved symptoms and calcifications. Pediatric intervertebral disc calcification is a rare cause of acquired torticollis, with a benign and self-limited outcome. Conservative management, as well as clinical and imaging follow-up is recommended.


Clinical and Retrospective Evaluation of 4.1- or 4.3-mm-Diameter Implants Placed Immediately in the Molar Region: A Preliminary Study.
The purpose of this study was to evaluate the clinical and radiographic performance of 4.1- or 4.3-mm-diameter implants placed immediately in the molar region. Twenty-nine patients (14 men and 15 women, aged 21-71 years) received 38 implants that were placed immediately in the molar region. Of the implants, 19 (50%) were placed in the maxilla and 19 (50%) in the mandible. Thirty-eight prostheses (19 single restoration and 19 partial fixed prostheses) were fabricated. The diameter of the implant type was 4.1 mm (15 implants, 39%) or 4.3 mm (23 implants, 61%). Clinical and radiographic assessments of implants, prostheses, and peri-implant tissues were performed at 1 month, 3 months, and 6 months and then every 6 months after definitive restoration. Kaplan-Meier survival estimates showed a 97.4% probability of implant survival to 36 months. The mean time of implant follow-up was 36 months, with a maximum of 75 months and minimum of 4 months. Cement dissolution occurred in 1 partial fixed prosthesis. Screw loosening occurred in 2 single-crown restorations in 1 patient. No abutment, screw, or implant fixture fractures were observed during the follow-up periods. The mean cervical bone loss of 38 implants measured 0.31 ± 0.06 mm mesially and 0.31 ± 0.07 mm distally 1 year after implant installation. There were no significant differences in implant survival and cervical bone loss based on anatomic location, gender, and prosthesis type. This study describes successful outcomes after the use of 4.1- or 4.3-mm-diameter implants placed immediately in the molar region. Further comprehensive maintenance practices and follow-up schedules are required.


Medical drones: Disruptive technology makes the future happen.
Trauma surgery has always been driven forward by innovative technological advancements. The recent appearance of "advanced air mobility" (AAM) represents one of the next steps in these technological developments. These innovative flying systems have major implications for all of the various healthcare stages in trauma surgery: Unmanned aircraft systems, or drones, can deliver critical supplies on demand, just in time, without physical contact, within the "last mile delivery" concept, such as AEDs, critical medication, blood for transfusion etc. Electric vertical take-off and landing (eVTOL) devices add new horizons for healthcare thanks to the smallest take-off and landing areas. These eVTOLs are not only new aircraft but, thanks to the autonomous flying options, they are flying computers with novel technological opportunities on board. With these new, flying operation systems, the whole rescue chain will be completely revolutionized by much faster response intervals, patient transportation times, telemedical applications, optimized emergency medical services, laboratory transportation etc. Hence, this article aims to provide a tentative overview of these new exciting technological developments in the field of trauma surgery for the benefit of our patients.


A Curious Case of Inhalation Fever Caused by Synthetic Cannabinoid.
This case report describes inhalation fever as an uncommon pulmonary adverse effect of synthetic cannabinoids. A 29-year-old man was brought in for severe agitation after smoking K2, a synthetic cannabinoid. He required multiple doses of lorazepam and haloperidol for sedation. His vital signs were notable for a mild fever and tachycardia. Otherwise, the rest of his exam was unremarkable. The laboratory test was significant for leucocytosis and diffuse reticular-nodular and interstitial infiltrates on chest radiograph. Urine drug toxicology was negative. Interestingly, his symptoms and pulmonary infiltrates on the chest radiograph resolved spontaneously after 24 hours of observation. This patient developed transient pulmonary infiltrates and fever following the synthetic cannabinoid inhalation, as seen in self-limiting inhalation fever. Inhalation fever as a consequence of synthetic cannabinoid has not been described previously and there is a need for further research in this field.


Surgery, chemotherapy and whole abdominal radiotherapy in the management of advanced ovarian carcinoma.
A pilot study on 35 women was performed to determine the feasibility of giving whole abdominal radiotherapy after surgery and chemotherapy for Stage III and IV ovarian adenocarcinoma. The planned duration of therapy was only 6 months from diagnosis. Chemotherapy consisted of four courses of cis-platinum 100 mg/m2 alternating every 10-12 days with four courses of methotrexate 300 mg/m2 and cyclophosphamide 500 mg/m2 followed by folinic acid rescue. Twenty-nine of 35 (83%) patients were shown at second look surgery after chemotherapy to have residual tumour deposits no more than 2 cm in diameter. The usual radiotherapy dose was 2400 cGy in 20 fractions over approximately 4 to 5 weeks, with kidney shielding, and was generally well tolerated. Three patients failed to complete radiotherapy, two because of progressive disease and one because of persistent nausea and vomiting. During radiotherapy the white blood count fell below 2.0 X 10(9)/litre in seven patients (26%), and in eight patients (30%) the platelet count fell below 75 X 10(9)/litre. However, the white blood count nadir of 1.5 X 10(9)/litre was reached by 1300 cGy and the platelet nadir of 45 X 10(9)/litre was reached by 1400 cGy and both then levelled or recovered despite continuing radiotherapy. The median follow up since diagnosis is 26 months. Four of 12 patients with no tumour detected at second look operation have relapsed compared with 13 of 15 patients who had detectable tumour. Toxicity of this multi-modality therapy was acceptable.


Low susceptibility of NC/Nga mice to tumor necrosis factor-alpha-mediated lethality and hepatocellular damage with D-galactosamine sensitization.
The susceptibility of NC/Nga mice to tumor necrosis factor (TNF)-alpha was examined by using sensitization with d-galactosamine (d-GalN). Administration of TNF-alpha and d-GalN killed none of the NC/Nga mice, whereas it killed all of the BALB/c mice. Treatment with TNF-alpha and d-GalN caused few hepatic lesions in NC/Nga mice but massive hepatocellular apoptosis in BALB/c mice. Unlike BALB/c mice, there was no elevation in caspase 3 and 8 activities in the livers of NC/Nga mice receiving TNF-alpha and d-GalN. On the other hand, administration of anti-Fas antibody definitely killed both NC/Nga and BALB/c mice via activation of caspases 3 and 8. Treatment with TNF-alpha and d-GalN led to translocation of nuclear factor (NF)-kappaB in NC/Nga and BALB/c mice. However, NF-kappaB translocation was sustained in NC/Nga mice, although it disappeared in BALB/c mice 7 h after the treatment. NF-kappaB inhibitors activated caspases 3 and 8, and enhanced TNF-alpha-mediated lethality in NC/Nga. Taken together, the low susceptibility of NC/Nga mice to TNF-alpha-mediated lethality was suggested to be responsible for the sustained NF-kappaB activation.


5-Bromomethyl fluorescein (5-BMF) for derivatization of carboxyl containing analytes for use with laser-induced fluorescence detection.
5-Bromomethyl fluorescein (5-BMF) was evaluated in this work as a pre-column, off-line derivatizing reagent for analytes containing a free carboxyl group. The reagent possessed high molar absorptivity and quantum yield and it's excitation maximum matched the intense 488.0 nm emission line of an argon ion laser. The thermal and photo-stability of the reagent were also suitable for our work. A mixture of 5-BMF, palmitic acid, 18-crown-6 and potassium carbonate was reacted at 76 degrees C for one hour. The reaction yield was maximized by a sequential single-factor optimization of the reaction variables. Spectral characterizations were accomplished using conventional instrumentation and detection limits were evaluated using a laboratory constructed laser-induced fluorescence (LIF) detector which was optimized for concentration detection. Two apparent conjugates of palmitic acid were formed under the reaction conditions employed. The conjugate chosen for quantitative purposes was stable at room temperature over 24 hours and possessed high molar absorptivity (128,832 M-1cm-1) and quantum yield (0.82) under basic conditions. The excitation and emission maxima of the conjugate were 500 nm and 523 nm respectively which maintains suitability for argon-ion laser excitation. An argon-ion LIF detector suitable for use with conventional liquid chromatography was constructed. A detection limit of 7.56 x 10(-10)M of palmitic acid was achieved at a signal to noise ratio of three, using the strong 488.0 nm laser emission line and a commercially available flow cell component. This corresponds to 38 femtomoles of palmitic acid on-column. The concentration detection limit was superior to literature reports for detection of fatty acids. The mass detection limit provided approximately an order of magnitude improvement over conventional fluorescence. The reagent is potentially useful for analysis of carboxyl containing analytes at low concentrations.


Induction of mitochondrial phosphoenolpyruvate carboxykinase in cultured human fibroblasts.
Mitochondria of cultured normal human fibroblast cells were found to contain the enzyme phosphoenolpyruvate carboxykinase. The activity of this enzyme in these cells is increased 2- to 3-fold by addition of 5 . 10(-4) M dibutyryl cyclic AMP, or 1.5- to 2-fold by the addition of dexamethasone (2 . 10(-7) M) or hydrocortisone (1.38 . 10(-6) M). These increases in enzyme activity were inhibited cycloheximide and actinomycin D, suggesting they are dependent upon de novo protein synthesis. Cultured human fibroblasts may thus provide a useful system for studying the regulation of mitochondrial phosphoenolpyruvate carboxykinase.


LncRNA MEG3 promotes cisplatin sensitivity of cervical cancer cells by regulating the miR-21/PTEN axis.
Cervical cancer (CC) is a common gynecological malignancy worldwide. Some patients perform serious resistance after chemotherapy, and long-stranded non-coding RNA MEG3 is reported to be involved in the regulation of chemoresistance in many solid tumors. However, its involvement in cervical adenocarcinoma has not been reported. Hela cell lines, cisplatin-resistant cell lines (Hela-CR) and nude mice were used in this study. After MEG3 was overexpressed or knocked down in cells by the lentivirus vector, cell growth was detected by the CCK-8 assay, and cell migration was evaluated using Transwell assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of MEG3, miR-21 and PTEN mRNA. Apoptosis was detected by flow cytometry. The targeting relationship between mRNAs was predicted and verified using dual-luciferase reporter gene experiments. Western blot was executed to examine Bax, cleaved-caspase 3, Bcl-2, PTEN and GAPDH expression. Cells were injected into the mice to form xenograft tumors to compare tumorigenesis capacity. We demonstrated that MEG3 was down-regulated in cervical cancer by analyzing the TCGA database. Moreover, knockdown of MEG3 promoted CC cell proliferation, migration and inhibited the apoptosis. These changes of CC cells were more pronounced under cisplatin treatment. Further studies showed that the MEG3/miR-21/PTEN axis affected cisplatin sensitivity in cervical cancer cells, and these results of recue assay were used to confirm this conclusion. MEG3 performing as ceRNA promotes cisplatin sensitivity in CC cells through the miR-21/PTEN axis.


Fluoxetine: a review of receptor and functional effects and their clinical implications.
Downregulation of serotonin 5-HT1 receptors is the most frequently reported central nervous system neural effect of subchronic exposure to fluoxetine in rodents. However, downregulation of these receptors has not been universally demonstrated. Effects of subchronic exposure on 5-HT2 receptors are mixed. Fluoxetine exposure appears to have no effect on cholinergic muscarinic receptors. Effects on beta-adrenergic receptors are controversial, as only one laboratory has reported downregulation. The majority of studies have failed to show an effect on beta-adrenergic-receptor-stimulated cAMP generation. Electrophysiologic studies support the concept that fluoxetine facilitates net serotonergic transmission through downregulation of presynaptic inhibitory autoreceptors. Data suggest that its subchronic specificity and selectivity distinguish fluoxetine from members of other classes of available antidepressants, making it a distinct therapeutic option.


Mutation of cysteine 46 in IKK-beta increases inflammatory responses.
Activation of IκB kinase β (IKK-β) and nuclear factor (NF)-κB signaling contributes to cancer pathogenesis and inflammatory disease; therefore, the IKK-β-NF-κB signaling pathway is a potential therapeutic target. Current drug design strategies focus on blocking NF-κB signaling by binding to specific cysteine residues on IKK-β. However, mutations in IKK-β have been found in patients who may eventually develop drug resistance. For these patients, a new generation of IKK-β inhibitors are required to provide novel treatment options. We demonstrate in vitro that cysteine-46 (Cys-46) is an essential residue for IKK-β kinase activity. We then validate the role of Cys-46 in the pathogenesis of inflammation using delayed-type hypersensitivity (DTH) and an IKK-β C46A transgenic mouse model. We show that a novel IKK-β inhibitor, dihydromyricetin (DMY), has anti-inflammatory effects on WT DTH mice but not IKK-β C46A transgenic mice. These findings reveal the role of Cys-46 in the promotion of inflammatory responses, and suggest that Cys-46 is a novel drug-binding site for the inhibition of IKK-β.


Topographical linkage of tecto-thalamo-anterior ectosylvian sulcal cortex in the cat: an 125I-WGA autoradiographic study.
Following injection of 125I-WGA into various parts of the caudal thalamus in the cat, the distribution of orthograde and retrograde labels in the cortex around the anterior ectosylvian sulcus (AESS) and the superior colliculus (SC) was examined autoradiographically. When 125I-WGA injections involved the medial part of nucleus lateralis posterior (Lp) of the thalamus, both orthograde and retrograde labels consistently appeared in the cortex around AESS, and retrograde labels in the SC. The topographical organization of the cortical connections with the medial part of Lp can be well correlated with that of the tecto-thalamic projections, in such a way that the dorsal portion of the medial part of Lp which receives fibers from the rostromedial part of SC is connected reciprocally with the lateral lip of AESS and the crown of the anterior sylvian gyrus; whereas, the most ventral portion of the medial part of Lp which receives tectal afferents from the caudolateral part of SC is connected with the dorsal bank and fundus of AESS. These results suggest the existence of retinotopically ordered linkage between the tecto-Lp and the Lp-AESS connections in the cat.


Alpha1beta1 integrin and interleukin-7 receptor up-regulate the expression of RANKL in human T cells and enhance their osteoclastogenic function.
Activated T cells, through the production of the receptor activator of NF-kappaB ligand (RANKL) cytokine, have been implicated in the osteoclast development and bone loss that are associated with autoimmune diseases such as rheumatoid arthritis. However, the cellular pathways that regulate the expression of RANKL and the induction of osteoclasts are still unclear. In this study, we show that, in human effector CD4(+) T cells, activation of alpha1beta1 integrin and interleukin (IL)-7 receptor (IL-7R) up-regulates the expression and production of RANKL but has no effect on the production of interferon-gamma, an inhibitor of T-cell-mediated osteoclastogenesis. Thus, both alpha1beta1 integrin and IL-7R enhance the ability of these cells to induce the formation of osteoclasts from human monocytes. Furthermore, we found that simultaneous activation of effector CD4(+) T cells via alpha1beta1 integrin and IL-7R synergistically increases the production of RANKL and enhances their osteoclastogenic function. We also show that, although alpha1beta1 integrin does not protect human effector CD4(+) T cells from IL-2-withdrawal-induced apoptosis, it does enhance the pro-survival effect of IL-7, further emphasizing the importance of the alpha1beta1/IL-7R synergistic effect. Together our results identify a new function of alpha1beta1 integrin in T cells and suggest that activation of effector CD4(+) T cells through alpha1beta1 integrin and IL-7R is an important regulatory pathway in T-cell-dependent osteoclastogenesis. Further understanding of the mechanisms by which IL-7R and alpha1beta1 integrin promote T-cell-mediated osteoclastogenesis will lead to new insights into the regulatory pathways of T-cell-dependent bone resorption associated with autoimmune diseases.


Glycolysis aggravates methotrexate toxicity by fueling RFC1-controlled intestinal absorption in rheumatic rats.
Methotrexate (MTX) is a first line anti-rheumatic drug. This study was designed to investigate the impact of rheumatoid arthritis (RA) conditions on its oral absorption, and clarify the relevance with changes of MTX absorption-related transporters in rheumatic models. MTX was orally administered to healthy, collagen-induced arthritis (CIA), and adjuvant-induced arthritis (AIA) rats. MTX plasma concentrations were determined by a validated liquid chromatography-mass spectrometry method. We found that intestinal MTX absorption was significantly increased in CIA/AIA rats versus healthy controls. This finding was supported by small intestine-based MTX uptake assay in vitro. Meanwhile, intestinal expression of both reduced folate carrier 1 (RCF1) and proton-coupled folate transporter (PCFT) remained unchanged. The everted intestinal sac assay confirms RFC1 is the key transporter accounting for intestinal MTX absorption, as its antagonist salicylazosulfapyridine showed potent capacity in reducing MTX uptake. No correlation between RA-related cytokines and RCF1 expression was observed in clinical samples. We further revealed that when cultured with AIA rat or RA patient serum, lactate and adenosine triphosphate (ATP) production as well as MTX uptake in MDCKII cells were significantly increased, and this increase was completely abrogated by ATP production-related metabolic inhibitors. Thanks to its inhibitory effects on MTX bioavailability, the glycolysis inhibitor shikonin diminished MTX-induced injuries of kidney and liver in AIA rats. These data demonstrate that glycolysis-driven high energy metabolism increases MTX absorption in rheumatic subjects, leading to the exacerbated toxicity. These findings will have important implications in optimizing MTX regimens for RA treatment with better efficacy and lower toxicity.


Ultrastructural and ultracytochemical studies on the blood-brain barrier in chronic relapsing experimental allergic encephalomyelitis.
We induced chronic relapsing experimental allergic encephalomyelitis (EAE), and studied the ultrastructural and ultracytochemical changes of the blood-brain barrier (BBB) in the demyelinating lesions of various stages of EAE. In the chronic, inactive stage with gliosis and perivascular fibrosis, the basal lamina (BL) of the perivascular processes of astrocytes was formed only partially, and neural parenchyma was not fully separated from the perivascular mesenchymal tissues by the BL of astrocytic processes. Vascular permeability of the BBB was studied using exogenous horseradish peroxidase (HRP) as the tracer: HRP extravasation was marked during the stages of both active myelin breakdown and removal of debris, and was recognized even at the inactive stage, although the degree was reduced to a very low level. The functions of the endothelia, assessed by ouabain-sensitive, K+-dependent p-nitrophenylphosphatase activity, were impaired as EAE progressed. The decrease in HRP leakage at the inactive stage suggests the endothelial impairment of active transport of metabolites including HRP. Along with the development of inflammatory demyelination in EAE, the BBB in affected areas became more and more altered, and gradual morphological and functional impairment of the BBB developed.


Effects of COVID-19 on school enrollment.
We estimate effects of the COVID-19 pandemic on self-reported school enrollment using a sample of 16-to-18-year-old youth from the January 2010 to the December 2020 Current Population Survey (CPS). The pandemic reduced the likelihood of students reporting that they were enrolled in high school by about 1.8 percentage points in April 2020 vs. in the same month in prior years, although enrollment rebounded back to typical levels by October 2020. Adverse effects on school enrollment were magnified for older vs. younger students, males vs. females, and among adolescents without a college-educated household member vs. adolescents from more educated households. Greater school responsiveness to the pandemic and high school graduation exit exams appear to have protected students from disengaging from school.


Extended cubic B-spline collocation method for singularly perturbed parabolic differential-difference equation arising in computational neuroscience.
A parameter uniform numerical method is presented for solving singularly perturbed parabolic differential-difference equations with small shift arguments in the reaction terms arising in computational neuroscience. To approximate the terms with the shift arguments, Taylor's series expansion is used. The resulting singularly perturbed parabolic differential equation is solved by applying the implicit Euler method in temporal direction and extended cubic B-spline basis functions consisting of a free parameter λ for the resulting system of ordinary differential equations in the spatial direction. The proposed method is shown to be accurate of order OΔt+h2ε+h by preserving an ε- uniform convergence. To demonstrate the applicability of the proposed method, two test examples are solved by the method and the numerical results are compared with some existing results. The obtained numerical results agreed with the theoretical results.


Tau accumulation in the retina promotes early neuronal dysfunction and precedes brain pathology in a mouse model of Alzheimer's disease.
Tau is an axon-enriched protein that binds to and stabilizes microtubules, and hence plays a crucial role in neuronal function. In Alzheimer's disease (AD), pathological tau accumulation correlates with cognitive decline. Substantial visual deficits are found in individuals affected by AD including a preferential loss of retinal ganglion cells (RGCs), the neurons that convey visual information from the retina to the brain. At present, however, the mechanisms that underlie vision changes in these patients are poorly understood. Here, we asked whether tau plays a role in early retinal pathology and neuronal dysfunction in AD. Alterations in tau protein and gene expression, phosphorylation, and localization were investigated by western blots, qPCR, and immunohistochemistry in the retina and visual pathways of triple transgenic mice (3xTg) harboring mutations in the genes encoding presenilin 1 (PS1M146 V), amyloid precursor protein (APPSwe), and tau (MAPTP301L). Anterograde axonal transport was assessed by intraocular injection of the cholera toxin beta subunit followed by quantification of tracer accumulation in the contralateral superior colliculus. RGC survival was analyzed on whole-mounted retinas using cell-specific markers. Reduction of tau expression was achieved following intravitreal injection of targeted siRNA. Our data demonstrate an age-related increase in endogenous retinal tau characterized by epitope-specific hypo- and hyper-phosphorylation in 3xTg mice. Retinal tau accumulation was observed as early as three months of age, prior to the reported onset of behavioral deficits, and preceded tau aggregation in the brain. Intriguingly, tau build up occurred in RGC soma and dendrites, while tau in RGC axons in the optic nerve was depleted. Tau phosphorylation changes and missorting correlated with substantial defects in anterograde axonal transport that preceded RGC death. Importantly, targeted siRNA-mediated knockdown of endogenous tau improved anterograde transport along RGC axons. Our study reveals profound tau pathology in the visual system leading to early retinal neuron damage in a mouse model of AD. Importantly, we show that tau accumulation promotes anterograde axonal transport impairment in vivo, and identify this response as an early feature of neuronal dysfunction that precedes cell death in the AD retina. These findings provide the first proof-of-concept that a global strategy to reduce tau accumulation is beneficial to improve axonal transport and mitigate functional deficits in AD and tauopathies.


Two initiation sites for translation of poliovirus RNA in vitro: comparison of LSc and Mahoney strains.
Previous studies in our laboratory provided evidence that the initiation of translation by the Mahoney strain of poliovirus type 1 RNA in vitro occurs at two unique sites. This study shows that the LSc strain of poliovirus type 1, a multistep, temperature-sensitive mutant of the Mahoney strain, also utilizes two sites for the initiation of translation in vitro. Incorporation of formyl-[35S]methionine into the amino terminus of newly synthesized polypeptides revealed the production of two labeled tryptic peptides which are identical in size and electrophoretic mobility with those produced by Mahoney virus. The polypeptides containing amino-terminal label showed similar patterns on sodium dodecyl sulfate-acrylamide gels, although one of the LSc polypeptides had a slightly faster mobility. The relative proportion of initiation at each site varied with the magnesium concentration for both viruses, but the LSc strain favored initiation at one site more so than did the Mahoney strain.


Production of omega-3 polyunsaturated fatty acids from cull potato using an algae culture process.
Algal cultivation for converting cull potato to docosahexaenoic acid (DHA) was studied. Schizochytrium limacinum SR21 was selected as the better producing strain, compared with Thraustochytrium aureum because of higher cell density and DHA content. Used as both carbon and nitrogen source, an optimal ratio of hydrolyzed potato broth in the culture medium was determined as 50%, with which the highest production of 21.7 g/L dry algae biomass and 5.35 g/L DHA was obtained, with extra glucose supplemented. Repeat culture further improved the cell density but not fed batch culture, suggesting limited growth was most likely caused by metabolites inhibition.


Design and analysis of an Actinobacillus pleuropneumoniae transmission experiment.
This paper describes a methodology to quantify the transmission of Actinobacillus (A.) pleuropneumoniae from subclinically infected carrier pigs to susceptible contact pigs, and to test the effect of possible interventions on the transmission. The methodology includes the design of a transmission experiment, and a method with which A. pleuropneumoniae transmission can be quantified and with which the effect of an intervention on the transmission can be tested. The experimental design consists of two parts. First, subclinically infected carrier pigs are created by contact exposure of specific-pathogen-free pigs to endobronchially inoculated pigs. Second, transmission is observed from the group of carrier pigs to a second group of susceptible contact pigs after replacing the inoculated pigs by new contact pigs. The presented analytical method is a generalised linear model (GLM) with which the effect of an intervention on the susceptibility and infectivity can be tested separately, if the transmission is observed in heterogeneous populations. The concept of the experimental transmission model is illustrated by describing an A. pleuropneumoniae transmission experiment in which the effect of vaccination on the susceptibility is quantified. Although it could not be demonstrated that vaccination has an effect on the susceptibility of pigs, it was demonstrated that nasal excretion of A. pleuropneumoniae is related to the infectivity of pigs.


Uncovering the protective mechanism of Huoxue Anxin Recipe against coronary heart disease by network analysis and experimental validation.
Coronary heart disease (CHD) is a leading cause of death and disability worldwide. Huoxue Anxin Recipe (HAR) is a novel Chinese Herbal Medicine formula of that has been used to treat CHD for several decades. Our previous study found that HAR had anti-oxidative effects, and could promote myocardial angiogenesis and improve cardiac function following myocardial infarction (MI) in rats. However, the active compounds, potential targets, and biological processes related to HAR have not been systematically investigated. Here, network pharmacology and experimental validation were used to study the protective mechanisms of HAR against CHD. We identified 124 active components, 124 verified targets, and 111 predictive targets. A total of 1192 genes related to CHD were identified by cDNA microarray and database analysis. A total of 47 putative targets of HAR against CHD were identified, including 32 verified targets and 15 predictive targets. ClueGo enrichment analysis identified 49 biological processes involved in the anti-CHD effects of HAR. Among them, the negative regulation of blood coagulation and regulation of collagen biosynthetic process were experimentally validated. After constructing a protein-protein interaction network and clustering with MECODE and ClusterONE, 162 key proteins (from ClueGo and clustering) were used to construct an internal interaction network. Complement C3 (C3), Fibrinogen alpha (FGA), Fibrinogen gamma (FGG), interleukin-6 (IL6), and Apolipoprotein A1 (APOA1) were the top 5 hub proteins identified by cytoHubber analysis. HAR limited the concentrations of C3, FGA, FGG, and IL6 and increased APOA1 levels. The results indicated that HAR could down-regulate blood coagulation, regulate collagen biosynthesis, inhibit peroxidation and inflammation injury, and promote cholesterol efflux. HAR could be a potential source of novel and effective drugs for CHD.


Compound heterozygosity for Hb S [beta6(A3)GluVal, GAG-->GTG] and a new thalassemic mutation [beta132(H10)Lys-->term, AAA-->TAA] detected in a family from West Africa.
We describe a Hb S/beta-thalassemia (beta-thal) mutation involving an AT transition at codon 132 of the beta-globin gene. The mutation, in the heterozygous state, unlike several other mutations in exon 3, shows no signs of dominant thalassemia but those of a typical beta(0) carrier. Compound heterozygosity with Hb S [beta6(A3)GluVal, GAGGTG] showed a severe clinical picture.


Sex and hormone dependent alterations in responsiveness to caloric dilution.
Potential sex differences in the long-term control of feeding behavior in rats was tested by comparing male and female rats in terms of their responsiveness to a 20 and 40 percent diet dilution challenge. During three-day test periods with both levels of diet dilution, female rats increased their daily food intake (FI) significantly more than did male rats. As a further index of greater precision in the long-term control of feeding behavior by female than by male rats, body weight (BWt) was less affected in female than in male rats during the caloric dilution challenges. In a second experiment, gonadectomy was found to attenuate this sexually dimorphic response to a 40% diet dilution test, whereas daily injections of gonadal hormones reestablished the sex difference in FI and BWt changes produced by the dilution challenge. Since responsiveness to the dilution challenge of female rats, but not males, was altered by gonadectomy and steroid treatment, it appears that estrogen shifts the control of feeding behavior in female rats towards more long-term factors.


Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review.
The onset of OA is affected by a variety of factors, which eventually lead to the loss of cartilage in the joints, the formation of osteophytes, the loss of normal knee mobility, and pain and discomfort, which seriously affects the quality of life. HUC-MSCs can promote cartilage production and have been widely used in research in the past decade. This article systematically summarizes that it is well used in basic research and clinical studies to promote inflammatory chondrogenesis in the treatment of OA. Provide a theoretical basis for clinical treatment. This study collected CNKI, Wanfang, PubMed, and articles related to the treatment of OA with HUC-MSCs since their publication, excluding non-basic and clinical studies such as reviews and meta-analysis. A total of 31 basic experimental studies and 12 clinical studies were included. Systematically analyze the effects of HUC-MSCs on inhibiting inflammatory factors, promoting chondrocyte production, and current clinical treatment. HUC-MSCs can reduce inflammatory factors such as MMP-13, ADAMTS-5, IL-1β, IL-1, IL-6, TNF-α, induced conversion from M1 to M2 in OA to protect cartilage damage and reduce OA inflammation. Synthesize ColII, SOX9, and aggrecan at the same time to promote cartilage synthesis. HUC-MSCs not only have typical stem cell biological characteristics, but also have rich sources and convenient material extraction. Compared with stem cells from other sources, HUC-MSCs have stronger proliferation, differentiation, and immune regulation abilities. Furthermore, there are no ethical issues associated with their use. Primarily attributed to pain, the majority of individuals experience recovery within 24 h following injection. HUC-MSCs possess the ability to alleviate pain, enhance knee joint function, and potentially postpone the need for surgical intervention in both non-surgical and other cases, making them highly deserving of clinical promotion and application.


[The contribution of German professors to pharmaceutical chemistry and phytochemistry in the 19th and 20th centuries. 40. The history of pharmaceutical science].
The aim of this article is to trace some features of the historical development of phytochemistry. In the period from 1870 to 1920 pharmacy at universities attempted a new phase, the emancipation as an independent science. The article analyses the contributions to phytochemistry by the professors E. Schmidt (1845-1921), H. Thomas (1859-1931), H. Beckurts (1855-1929) and their research schools as well as those of K. Polstorff (1846-1911) and m. Scholtz (1861-1919).


Somatotopical feedback versus non-somatotopical feedback for phantom digit sensation on amputees using electrotactile stimulation.
Transcutaneous electrical stimulation can provide amputees with tactile feedback for better manipulating an advanced prosthesis. In general, there are two ways to transfer the stimulus to the skin: somatotopical feedback (SF) that stimulates the phantom digit somatotopy on the stump and non-somatotopical feedback (NF) that stimulates other positions on the human body. To investigate the difference between SF and NF, electrotactile experiments were conducted on seven amputees. Electrical stimulation was applied via a complete phantom map to the residual limb (SF) and to the upper arm (NF) separately. The behavior results of discrimination accuracy and response time were used to examine: 1) performance differences between SF and NF for discriminating position, type and strength of tactile feedback; 2) performance differences between SF and NF for one channel (1C), three channels (3C), and five channels (5C). NASA-TLX standardized testing was used to determine differences in mental workload between SF and NF. The grand-averaged discrimination accuracy for SF was 6% higher than NF, and the average response time for SF was 600 ms faster than NF. SF is better than NF for position, type, strength, and the overall modality regarding both accuracy and response time except for 1C modality (p<0.001). Among the six modalities of stimulation channels, performance of 1C/SF was the best, which was similar to that of 1C/NF and 3C/SF; performance of 3C/NF was similar to that of 5C/SF; performance of 5C/NF was the worst. NASA-TLX scores indicated that mental workload increased as the number of stimulation channels increased. We quantified the difference between SF and NF, and the influence of different number of stimulation channels. SF was better than NF in general, but the practical issues such as the limited area of stumps could constrain the use of SF. We found that more channels increased the amount and richness of information to the amputee while fewer channels resulted in higher performance, and thus the 3C/SF modality was a good compromise. Based on this study, we provide possible solutions to the practical problems involving the implementation of tactile feedback for amputees. These results are expected to promote the application of SF and NF tactile feedback for amputees in the future.


The puzzle of kidney dysfunction in heart failure: an introduction.
Heart failure and kidney disease often coexist, and each of the two conditions may lead to progression of the other. Kidney dysfunction is an independent prognostic factor in patients with either acute or chronic heart failure. Worsening renal function may be related with poorer outcomes as well. Multiple mechanisms are involved in the cardio-renal interaction, including hemodynamic abnormalities, neurohormonal and inflammatory activation, oxidative stress, anemia, and abnormalities in mineral and vitamin D metabolism. Serum creatinine has limitations for the assessment of kidney function in patients with heart failure as its short-term changes are dependent on hemodynamic changes and fluid status. New biomarkers of glomerular and tubular function might allow an earlier and more accurate detection of worsening renal function.


Keep oxygen in check: An improved in-situ zymography approach for mapping anoxic hydrolytic enzyme activities in a paddy soil.
Paddy soils regularly experience redox oscillations during the wetting and draining stages, yet the effects of short-term presence of oxygen (O2) on in-situ microbial hotspots and enzyme activities in anoxic ecosystems remain unclear. To fill this knowledge gap, we applied soil zymography to localize hotspots and activities of phosphomonoesterase (PME), β-glucosidase (BG), and leucine aminopeptidase (LAP) in three compartments of rice-planted rhizoboxes (top bulk, rooted, and bottom bulk paddy soil) under oxic (+O2) and anoxic (O2) conditions. Short-term (35 min) aeration decreased PME activity by 13-49 %, BG by 4-52 %, and LAP by 12-61 % as compared with O2 in three soil compartments. The percentage of hotspot area was higher by 3-110 % for PME, by 10-60 % for BG, and by 12-158 % for LAP under +O2 vs. O2 conditions depending on a rice growth stage. Irrespective of the aeration conditions, the rhizosphere extent of rice plants for three enzymes was generally greater under higher moisture conditions and at earlier growth stage. Higher O2 sensitivity for the tested enzymes at bottom bulk soil versus other compartments suggested that short-term aeration during conventional zymography may lead to underestimation of nutrient mobilization in subsoil compared to top bulk soil. The intolerance of anaerobic microorganisms against the toxicity of O2 in the cells and the shift of microbial metabolic pathways may explain such a short-term suppression by O2. Our findings, therefore, show that anoxic conditions and soil moisture should be kept during zymography and probably other in-situ soil imaging methods when studying anoxic systems.


Two new alkaloids and active anti-hepatitis B virus constituents from Hypserpa nitida.
Two new alkaloids, hypserpanines A and B (1, 11), together with eleven known compounds, phenolbetain (2), acutumine (3), acutumidine (4), dechloroacutumine (5), dauricumine (6), dauricumidine (7), pronuciferine (8), glaziovine (9), S-reticuline (10), magnoflorine (12) and laurifoline(13), were isolated from Hypserpa nitida Miers. (Menispermaceae) and chemically elucidated through spectral analyses. All the isolated alkaloids were evaluated for their anti-HBV activities in vitro using the HBV transfected Hep G2.2.15 cell line. The most active compound, dauricumidine (7), exhibited an IC(50) value of 0.450 mM (SI=4.13) on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line.


Near-infrared fluorescence cholangiography in dogs: A pilot study.
To determine the effect of indocyanine green (ICG) dose and timing of administration on near-infrared fluorescence (NIRF) imaging of the normal canine biliary tree. Preclinical prospective study. Eight purpose-bred beagles. The dogs were randomized to receive two of four intravenous ICG dose (low [L]:0.05 mg/kg or high [H]:0.25 mg/kg)/time (0 and 3 h prior to NIRF) combinations. NIRF images were collected every 10 min for 120 min. Target (cystic duct)-to-background (liver) ratios were calculated for all timepoints and compared. ICG cholangiography was successful in all dogs. The contrast ratio was above 1 in the L0 group by 20 min and reached its peak at 100 min. In the H0 group, the ratio was above 1 by 60 min and reached its peak at 90 min. Contrast ratios above 2 (fluorescence twice as bright in the cystic duct compared to the liver) were maintained from 180 to 300 min for L3 and H3 and was achieved after 80 min for L0. Low dose ICG provided better ratios early after injection compared to the high dose which remained highly concentrated in the liver tissue after injection. Both doses provided excellent visualization of the biliary tree at 3 h post injection, low dose ICG provided better ratios from 3 to 5 h post injection. Based on these results, 0.05 mg/kg of ICG administered at anesthetic premedication, or as early as 3 h prior to laparoscopic surgery should yield optimal fluorescence images. This study provides guidelines for NIRF cholangiography in clinically normal dogs.


A new urea adducts method for PUFA concentration using green food grade solvents and avoiding ethyl carbamate formation.
This study aimed to selectively enrich stearidonic acid (SDA) together with γ-linolenic acid (GLA) in Echium plantagineum oil by urea complexation. The complexation process at room temperature was carried out replacing common organic solvents, such as hexane and ethanol, by alternative compounds, included in Green Solvent and Food Grade categories, adapting this process towards the principles of Green Chemistry. This substitution was also intended to avoid the generation of the toxic compound ethyl carbamate. Among all the solvents studied, the mixture propionic acid and α-pinene provided the best results, leading to a final product comprised of ∼99% of PUFA, with ∼45% SDA (∼14% in the original oil), and without apparition of ethyl carbamate. The procedure was tested on other raw materials (salmon and microalgae oils). The solvent was efficiently recuperated from the liquid phase (∼87% recovery) and reutilized once with almost identical results.


An Excerpt from The Anatomy of Murder: Excerpted from the Section: "The Pernkopf Controversy" (pages 278 - 281, 287, 288).
(Reprinted with permission from The Anatomy of Murder: Ethical Transgressions and Anatomical Science During the Third Reich. "The Pernkopf Controversy," pages 278-281; excerpted from Berghahn Books, 2016).


Modifications of Multi Slit Knife for Enhanced Versatility in Balding and Vertex Area Hair Transplant.
In hair transplantation, recipient-site creation is an important step. It is a repetitive and time-consuming step, which increased the "out-of-body time" for the grafts, which could hamper their survival. To solve this problem, we had devised an instrument called the Multi Slit Knife (MSK). The MSK has advantages of creating a high-density brick pattern of recipient sites in significantly less time. It had the undesirable side effect of damaging the preexisting hair follicles while making slits in the balding region. The MSK had some limitations. It was also difficult to maneuver the MSK in the vertex region where maintaining the natural whorl pattern of hair is important to obtain optimal aesthetic results. To overcome the shortcomings of the original MSK, we made a few changes to it to make a new modified MSK. It has fewer knives and a smaller platform as compared to the original MSK, better ergonomics, and more customizability with choices for blade sizes, number, and spacing. It tries to retain the advantages of the original MSK while reducing the damage to the preexisting hairs in the recipient regions. It is also better adapted at creating the recipient sites in a whorl pattern, closely mimicking the natural direction and angles of the hair in the vertex region. The modified MSK can be used singly or in combination with the original MSK, based on the patient's recipient areas, making it a versatile set of instrument for making multiple coronal slits for hair transplant.


Altering the characteristics of a leaf litter-derived humic substance by adsorptive fractionation versus simulated solar irradiation.
Changes in the characteristics of a leaf litter-derived humic substance (LLHS) that resulted from its adsorption onto kaolinite or exposure to simulated solar irradiation were tracked using selected spectroscopic descriptors, apparent weight-average molecular weight (MW(w)) and pyrene binding. Heterogeneity within the original bulk LLHS was confirmed by a range of different characteristics obtained from ultrafiltration-based size fractions. In general, trends of some changing LLHS characteristics were similar for the adsorption and irradiation processes when tracked against percent carbon removal. For example, the overall values of specific ultraviolet absorbance (SUVA), MW(w), and humification index (HIX) all decreased with increasing irradiation time and with increasing concentration of mineral adsorbent in the respective experiments, indicating that both processes resulted in less aromatic and smaller-sized LLHS components remaining in solution. In addition, both the adsorption and irradiation experiments resulted in enrichment of the relative distribution of protein-like fluorescence (PLF), implying the PLF-related components had low affinities for phototransformation and mineral surface adsorption. Despite these apparently similar overall trends in LLHS characteristics caused by the adsorption and irradiation processes, closer examination revealed considerable differences in how the two processes altered the original material. Net production of intermediate-sized constituents was observed only with the irradiation experiments. In addition, residual LLHS resulting from the adsorptive fractionation experiments exhibited consistently higher pyrene binding versus the irradiated LLHS despite having comparable MW(w) values. Changes in LLHS characteristics due to adsorption by kaolinite were likely caused by physical mechanisms (primarily hydrophobic interactions between LLHS components and the kaolinite surface) whereas the irradiation-induced changes appear to have been governed by the combined effects of several alteration mechanisms, including the transformation of more condensed aromatic structures to less aromatic constituents, conformational changes resulting from selective photooxidation, and the photochemical disruption of intramolecular charge-transfer interactions.


Visual guidance of landing behaviour when stepping down to a new level.
When stepping down from one level to another, the leading limb has to arrest downward momentum of the body and subsequently receive and safely support bodyweight before level walking can begin. Such step downs are performed over a wide range of heights and predicting when and where contact between the landing limb and the lower level will be made is likely a critical factor. To determine if visual feedback obtained after movement initiation is habitually used in guiding landing behaviour, the present study determined whether pre-landing kinematics and the mechanics of landing would be modulated according to the type of visual feedback available during the stepping down phase. Ten healthy participants (32.3 +/- 7.9 years) stepped, from a standing position, down from three different heights onto a forceplatform, either coming immediately to rest or proceeding directly to walking across the laboratory. Repeated trials were undertaken under habitual vision conditions or with vision blurred or occluded 2-3 s prior to movement initiation. Pre-landing kinematics were assessed by determining, for the instant of landing, lead-limb knee and ankle angle, stepping distance, forwards positioning of the body CM within the base of support and the forwards and downwards body CM velocity. Landing mechanics for the initial contact period were characterized using lead limb vertical loading and stiffness, and trail limb un-weighting. When vision was occluded movement time, ankle plantarflexion and knee flexion were significantly increased compared to that determined for habitual vision, whereas forwards body CM positioning and velocity, vertical loading and stiffness, and trail limb un-weighting, were significantly reduced (p < 0.05). Similar adaptations were observed under blurred conditions, although to a lesser extent. Most variables were significantly affected by stepping task and step height. Subjects likely reduced forwards CM position and velocity at instant of landing, in order to keep the CM well away from the anterior border of the base of support, presumably to ensure boundary margins of safety were high should landing occur sooner or later than expected. The accompanying increase in ankle plantarflexion at instant of landing, and increase in single limb support time, suggests that subjects tended to probe for the ground with their lead limb under modified vision conditions. They also had more bodyweight on the trail limb at the end of the initial contact period and as a consequence had a prolonged weight transfer time. These findings indicate that under blurred or occluded vision conditions subjects adopted a cautious strategy where by they 'sat back' on their trail limb and used their lead limb to probe for the ground. Hence, they did not fully commit to weight transfer until somatosensory feedback from the lead limb confirmed they had safely made contact. The effect of blurring vision was not identical to occluding vision, and led to several important differences between these conditions consistent with the use of impoverished visual information on depth. These findings indicate that online vision is customarily used to regulate landing behaviour when stepping down.


Spatial distribution, source apportionment and potential ecological risk assessment of suspended atmosphere microplastics in different underlying surfaces in Harbin.
Although suspended atmospheric microplastics (SAMPs) have been found to be ubiquitous and have potential impacts on human health, whereas studies related to source apportionment and potential ecological risk assessment in the atmospheric environment are still limited. This study investigated spatial distribution, source apportionment and potential ecological risk of SAMPs in six underlying surfaces of Harbin, China. The results show that all six underlying surfaces existed SAMPs, including polypropylene (PP), polyethylene terephthalate (PET) polyethylene (PE), polystyrene (PS) and polyvinyl chloride (PVC), with approximate 26.13 %, 24.10 %, 23.87 %, 13.51 %, and 12.39 %, respectively. SAMPs abundances from filtered air were relatively high and averaged 1.76 n/m3. The SAMPs mainly contained fibrous (59.01 %), fragmented (30.18 %), and granular (10.81 %) with transparent (62.39 %), black 13.74 %), red (7.43 %), white (6.53 %), blue, and yellow (3.60 %), and particle size ranged from 1.3 to 518 μm. In addition, source apportionment of SAMPs shows that SAMPs were originated from five emission sources including living source (19.53 %), construction source (12.08 %), transportation source (47.25 %), industrial source (5.11 %), and agricultural source (16.13 %) in Harbin. A significant correction was observed between SAMPs abundances and human activity (R = 0.68, P = 0.66), atmospheric humidity (R = -0.40, P = 0.02), and wind direction (R = 0.22, P = 0.04) in different underlying surface. Furthermore, potential ecological hazardous single index (EI) of PVC and PS were higher than PP, PET, and PS in the construction land, cultivated land, forest land, grassland, water area, and unused land. An estimation of the potential ecological risk index (RI) from SAMPs using Positive Matrix Factorization (PMF) model indicated that Harbin presented a minor ecological risk with average 16.59 of RI index of microplastics in environments. In conclusion, data in this study indicate that SAMPs are existed in atmospheric environments, which have possible risks for human health via inhalation.


High Color-Rendering Index and Stable White Light-Emitting Diodes by Assembling Two Broadband Emissive Self-Trapped Excitons.
White light-emitting diodes (WLEDs) are promising next-generation solid-state light sources. However, the commercialization route for WLED production suffers from challenges in terms of insufficient color-rendering index (CRI), color instability, and incorporation of rare-earth elements. Herein, a new two-component strategy is developed by assembling two broadband emissive materials with self-trapped excitons (STEs) for high CRI and stable WLEDs. The strategy addresses effectively the challenging issues facing current WLEDs. Based on first-principles thermodynamic calculations, copper-based ternary halides composites, CsCu2 I3 @Cs3 Cu2 I5 , are synthesized by a facile one-step solution approach. The composites exhibit an ideal white-light emission with a cold/warm white-light tuning and a robust stability against heat, ultraviolet light, and environmental oxygen/moisture. A series of cold/warm tunable WLEDs is demonstrated with a maximum luminance of 145 cd m-2 and an external quantum efficiency of 0.15%, and a record high CRI of 91.6 is achieved, which is the highest value for lead-free WLEDs. Importantly, the fabricated device demonstrates an excellent operation stability in a continuous current mode, exhibiting a long half-lifetime of 238.5 min. The results promise the use of the hybrids of STEs-derived broadband emissive materials for high-performance WLEDs.


An immunoenzyme quantitative assay for the antiviral effect of interferons.
A technique is described for measurement of the antiviral activity of interferon by an immunoenzymatic assay for viral proteins. Cells treated by tested samples of interferon (IFN) are infected with vesicular stomatitis virus (VSV) and following the development of viral cytopathy are lysed by the addition of deoxycholate and then transferred into ELISA microplates. The viral proteins bind effectively to the microplates proportionally to their level in the culture and may be measured by incubating the plates sequentially with (1) rabbit antiserum against VSV, (2) a conjugate of alkaline phosphatase either to protein A or to an antibody against rabbit IgG and (3) p-nitrophenylphosphate. This procedure may be further simplified by using antibodies against VSV to which alkaline phosphatase has been directly conjugated. We found this immunoenzyme assay to be superior to the 'cytopathic effect inhibition' assay in precision and sensitivity and in being independent of the effectiveness of viral cytopathy.


Private doctors and tuberculosis control in India.
Over three quarters of the 8 million registered doctors in India are engaged in private medical practice. In urban and rural areas alike people prefer private doctors to public health services for their health care needs. A majority of patients and those with suspected tuberculosis also report first to private doctors. Nevertheless private doctors seem to be alienated from national efforts towards control of tuberculosis, there being no well-defined role for them in the National Tuberculosis Programme. This study of private doctors practising in the low income areas of a metropolis of India reports on the knowledge of private doctors about diagnosis and treatment of tuberculosis and their awareness and perceptions about the public health services available for tuberculosis control. The study reveals gaps and weaknesses in the private doctors' reported practice of managing lung tuberculosis, the most important and persistent problem of public health concern in India. The need for organized efforts towards involving private doctors in disease control programmes wherein their curative functions could contribute significantly is stressed.


Sexual dimorphism of the hip joint in Greeks.
The objective of the present study was to report our measurements of hip bones within the Greek population and review the possible implications of these differences in their health as well as in social life. For this purpose the remains of 100 male and 100 female pelvic and femoral bones were studied. The distance from the pubic tubercle to the anterior rim of the acetabulum, the acetabulum diameter between its rims, their ratio, the depth of the acetabulum, the diameter of the femoral head and the ratio between the femoral head and the diameter of the acetabulum were measured. It was found that in males, in comparison to the females, the distance from the pubic tubercle to the anterior rim of the acetabulum was smaller while the acetabulum diameter and its depth, the diameter of the femoral head and the ratio between femoral head and the acetabulum diameter were larger. The above differences reached strong statistical significance. Of the two ratios used only the first one reached statistical significance. Using this ratio alone offered the best discrimination rate of up to 99% and should be the preferred choice when available.


A primer on population health: a new resource for students and clinicians.
This is one of six short papers that describe additional innovations that support the integration of public health into medical education. These were featured in the "Patients and Populations: Public Health in Medical Education" conference and describe innovative endeavors or curricular components not previously published. This paper describes the Association of Faculties of Medicine of Canada's Primer in Population Health and its collaborative development with contributions from all Canadian medical schools, in particular from the medical faculties of the University of Ottawa and the Université de Sherbrooke. Although evaluation data will not be available until the primer has been in use for at least 1 year, sharing a description of it is of potential value to medical educators.


Vascular adhesion protein-1 enhances neutrophil infiltration by generation of hydrogen peroxide in renal ischemia/reperfusion injury.
Vascular adhesion protein-1 (VAP-1) is a unique molecule since it acts as an adhesion molecule as well as an ectoenzyme catalyzing oxidative deamination of primary amines and generates hydrogen peroxide in the extracellular space. While VAP-1 is implicated in various inflammatory diseases, its role in acute kidney injury is less characterized. Here we studied VAP-1 expression in the kidney and the effect of its inhibition in a rat model of renal ischemia/reperfusion injury. VAP-1 was predominantly expressed in pericytes, which released enzymatically active enzyme. In vivo, a specific VAP-1 inhibitor, RTU-1096, significantly ameliorated rat renal ischemia/reperfusion injury and decreased neutrophil infiltration measured 12 hours after injury without altering macrophage or T lymphocyte populations. The protective effect of VAP-1 inhibition was lost in neutrophil-depleted rats, suggesting its inhibition ameliorated renal ischemia/reperfusion injury by suppressing neutrophil infiltration. To investigate whether hydrogen peroxide generated by VAP-1 enzyme reaction enhances neutrophil infiltration, we conducted an under-agarose migration assay with purified human neutrophils. Recombinant human VAP-1 significantly induced neutrophil migration, which was almost completely inhibited by RTU-1096 or catalase. Thus, VAP-1 plays a critical role in the pathophysiology of renal ischemia/reperfusion injury by enhancement of neutrophil infiltration generating a local hydrogen peroxide gradient. Hence, VAP-1 inhibition may be a novel therapy in ischemic acute kidney injury.


Cause of parental death and child's health and education: The role of parental resources.
Early parental death has been linked to problems in health and educational path. We added to the literature by examining disability pension and various educational outcomes after external (accident, violence, suicide) or natural parental death during childhood or adolescence, taking into account possible heterogeneous associations by parental resources. Using Finnish register data and linear random-effects models, we analysed outcomes of 90,620 and 88,859 children (paternal and maternal death samples, respectively) born between 1982 and 1990. Results indicated lower educational performance and attainment, and a higher probability of disability pension in the bereaved offspring, especially after external parental death. Half of these connections were explained after adjusting for childhood family characteristics. Having a highly educated surviving parent might protect from negative educational and health outcomes. The findings were partly similar for father's and mother's deaths. We demonstrated that the negative associations between parental death and child wellbeing differ by cause of death and parental resources. Cause of death and overall family circumstances should both be considered when analysing child outcomes after parental loss.


Treatment of Wilms tumor according to SIOP 9 protocol in Casablanca, Morocco.
Childhood Wilms tumor represents one of the challenge for pediatric oncologists in developing countries. We report the characteristics and treatment results of patients with Wilms tumor according to SIOP 9 protocol in Morocco. From January 1989 to December 2000, 86 children with Wilms tumor were admitted. The diagnosis was based on physical exam and abdominal ultrasound. The metastatic work-up was based on abdominal ultrasound and chest X-ray. The mean age was 36 months (3-120 months). The sex-ratio was 1. Abdominal mass was the main symptom at presentation (84 cases). There were 13 metastatic cases. Treatment applied was according to SIOP 9 Protocol without randomization. Local deases was present in 75 patients with stage I in 38 cases (50%), IIN0 in 4 cases (6%), IIN1 in 9 cases, and III in 24 cases (44%). The distribution of pathologic groups was: favorable in 4 cases, standard in 69 cases, and unfavorable anaplastic type in 2 cases. Sixty-nine patients were evaluable for therapeutic evaluation. Other patients were lost to follow-up. Three patients died of treatment related toxicity and 13 patients relapsed. With a median follow-up of 70 months, the 5-year EFS and 5 years overall survival for evaluable patients are 77.4% and 79%, respectively while the 5-year EFS for all patients was 56%. These results are encouraging for a developing country but special efforts should be done to reduce the rate of abandonment.


Randomized controlled trial of the effect of daily supplementation with zinc or multiple micronutrients on the morbidity, growth, and micronutrient status of young Peruvian children.
Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur. The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children's morbidity and physical growth. Two hundred forty-six children aged 6-35 mo with persistent diarrhea were randomly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone (Zn; n = 81), zinc plus vitamins and other minerals at 1-2 times recommended daily intakes (Zn+VM; n = 82), or placebo (n = 83) for approximately 6 mo after the diarrhea episode ended. Morbidity information was collected on weekdays. Weight, length, and other anthropometric indicators were measured monthly, and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo. Supplement consumption was high ( approximately 90%) in all groups, although slightly more vomiting was reported in the Zn+VM group (P < 0.0001, analysis of variance). The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups (6.1, 27.3, and 16.2 micro g/dL in the placebo, Zn, and Zn+VM groups, respectively; P < 0.0001, analysis of variance). The Zn group had fewer episodes of diarrhea, dysentery, and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group (P = 0.05). No significant effects of supplementation on growth were observed. Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone.


Cost-effective flow injection amperometric system with metal nanoparticle loaded carbon nanotube modified screen printed carbon electrode for sensitive determination of hydrogen peroxide.
Various metal nanoparticles (NPs) decorated on carbon nanotube (CNT) was modified on the home-made screen printed carbon electrode (SPCE) in order to enhances sensitivity of hydrogen peroxide (H2O2) determination. The simple casting method was used for the electrode modification. The monometallic and bimetallic NPs modified electrodes were investigated for their electrochemical properties for H2O2 reduction. The Pd-CNT/SPCE is appropriated to measure the H2O2 reduction at a potential of -0.3 V, then this modified electrode was incorporated with a home-made flow through cell and applied in a simple flow injection amperometry (FI-Amp). Some parameters influencing the resulted modified electrode and the FI-Amp system were studied. The proposed detection system was able to detect H2O2 in the range of 0.1-1.0 mM, with detection limit of 20 µM. Relative standard deviation for 100 replicated injections of 0.6 mM H2O2 was 2.3%. The reproducibility of 6 electrodes preparing in 3 different lots was 8.2%. It was demonstrated for determination of H2O2 in disinfectant, hair colorant and milk samples. Recoveries in the range of 90-109% were observed. The developed system provided high stability, good repeatability, high sample throughput and low reagent consumption.


The model structure of the copper-dependent ammonia monooxygenase.
Ammonia monooxygenase is a copper-dependent membrane-bound enzyme that catalyzes the first step of nitrification in ammonia-oxidizing bacteria to convert ammonia to hydroxylamine, through the reductive insertion of a dioxygen-derived O atom in an N-H bond. This reaction is analogous to that carried out by particulate methane monooxygenase, which catalyzes the conversion of methane to methanol. The enzymatic activity of ammonia monooxygenase must be modulated to reduce the release of nitrogen-based soil nutrients for crop production into the atmosphere or underground waters, a phenomenon known to significantly decrease the efficiency of primary production as well as increase air and water pollution. The structure of ammonia monooxygenase is not available, rendering the rational design of enzyme inhibitors impossible. This study describes a successful attempt to build a structural model of ammonia monooxygenase, and its accessory proteins AmoD and AmoE, from Nitrosomonas europaea, taking advantage of the high sequence similarity with particulate methane monooxygenase and the homologous PmoD protein, for which crystal structures are instead available. The results obtained not only provide the structural details of the proteins ternary and quaternary structures, but also suggest a location for the copper-containing active site for both ammonia and methane monooxygenases, as well as support a proposed structure of a CuA-analogue dinuclear copper site in AmoD and PmoD.


Mouse mutants as models for congenital retinal disorders.
Animal models provide a valuable tool for investigating the genetic basis and the pathophysiology of human diseases, and to evaluate therapeutic treatments. To study congenital retinal disorders, mouse mutants have become the most important model organism. Here we review some mouse models, which are related to hereditary disorders (mostly congenital) including retinitis pigmentosa, Leber's congenital amaurosis, macular disorders and optic atrophy.


Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (TAPSE) among out-patients referred for the evaluation of heart failure.
Prevalence, predictors, and prognostic value of right ventricular (RV) function measured by the tricuspid annular plane systolic excursion (TAPSE) in patients with chronic heart failure (CHF) symptoms with a broad range of left ventricular ejection fraction (LVEF) are unknown. Of 1,547 patients, mean (±SD) age was 71 ± 11 years, 48% were women, median (interquartile range [IQR]) TAPSE was 18.5 (14.0-22.7) mm, mean LVEF was 47 ± 16%, 47% had LVEF ≤45% and 67% were diagnosed with CHF, defined as systolic (S-HF) if LVEF was ≤45% and as heart failure with preserved ejection fraction (HFPEF) if LVEF was >45% and treated with a loop diuretic. During a median (IQR) follow-up of 63 (41-75) months, mortality was 34%. In multivariable analysis, increasing age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, right atrial volume index, and transtricuspid pressure gradient; lower TAPSE, diastolic blood pressure, and hemoglobin; and atrial fibrillation (AF) or COPD were associated with an adverse prognosis. Receiver operating characteristic curve analysis identified a TAPSE of 15.9 mm as the best prognostic threshold (P = .0001); 47% of S-HF and 20% of HFPEF had a TAPSE of <15.9 mm. The main associations with a TAPSE <15.9 mm were higher NT-proBNP, presence of atrial fibrillation and presence of LV systolic dysfunction. In patients with CHF, low values for TAPSE are common, especially in those with reduced LVEF. TAPSE, unlike LVEF, was an independent predictor of outcome.


The 1968 Influenza Pandemic and COVID-19 Outcomes.
Past pandemic experience can affect health outcomes in future pandemics. This paper focuses on the last major influenza pandemic in 1968 (H3N2), which killed up to 100,000 people in the US. We find that places with high influenza mortality in 1968 experienced 1-4% lower COVID-19 death rates. Our identification strategy isolates variation in COVID-19 rates across people born before and after 1968. In places with high 1968 influenza incidence, older cohorts experience lower COVID-19 death rates relative to younger ones. The relationship holds using county and patient-level data, as well as in hospital and nursing home settings. Results do not appear to be driven by systemic or policy-related factors, instead suggesting an individual-level response to prior influenza pandemic exposure. The findings merit investigation into potential biological and immunological mechanisms that account for these differences-and their implications for future pandemic preparedness.


Binding of complement component C1q by rat adipocyte membranes.
Human C1q was found to bind to rat adipocyte membranes with an affinity comparable to that for aggregated immunoglobulin. The binding was ionic strength dependent, and modification of arginyl and histidyl residues in C1q abrogated its binding activity. Treatment of the adipocyte membranes with either high ionic strength buffers, EDTA or trypsin had little effect on their C1q-binding activity.


Salmonella Typhi and Paratyphi A infections in Cambodian children, 2012-2016.
Enteric fever remains an important diagnostic and treatment challenge in febrile children living in the tropics. In the context of a national Salmonella enterica serovar Paratyphi A outbreak, the objective of this retrospective study was to compare features of S. Typhi and S. Paratyphi A infections in Cambodian children. Clinical and laboratory features were reviewed for 192 blood culture-confirmed children with S. Typhi and S. Paratyphi A infections presenting to a paediatric referral hospital in Siem Reap, 2012-2016. Children with S. Typhi infections were younger, were more likely to have chills and/or diarrhoea, and were more frequently hospitalized than those with S. Paratyphi A infections. Over three quarters (88.3%) of S. Typhi isolates were multidrug-resistant, compared to none of the S. Paratyphi A. In this small study of Cambodian children, S. Typhi infections were more severe than S. Paratyphi A infections. Antibiotic resistance limits treatment options for enteric fever in this population.


Thyroparathyroidectomy modifies the skeletal response to aluminum loading in the rat.
Diminished parathyroid hormone (PTH) secretion may contribute to the accumulation of aluminum (Al) in bone and to impaired bone formation in Al-related bone disease. Therefore, intact (AL, N = 9) and thyroparathyroidectomized (TPTX-AL, N = 9) rats were given intraperitoneal injections of Al, 2 mg/day, for 42 days; intact control (C, N = 11) and TPTX control (TPTX-C, N = 9) animals received i.p. injections of vehicle only. Quantitative bone histology and measurements of mineralized bone formation (Rbf) using double tetracycline labeling were done for cortical and for trabecular bone; trabecular bone aluminum content (BA) was determined by histochemical methods. BA did not differ between AL and TPTX-AL, 33 +/- 13% versus 39 +/- 14%, and Rbf decreased similarly from control values in both Al-treated groups. In contrast, osteoid production was impaired to a greater extent in TPTX-AL than in AL. Thus, osteoid area and osteoid seam width were each lower in TPTX-AL than in TPTX-C; these values did not differ between AL and C. TPTX can aggravate Al induced reductions in osteoid synthesis, and low serum PTH levels may contribute to the pathogenesis of aplastic bone. However, reductions in Rbf during Al loading are not mediated by PTH.


Activity of left inferior frontal gyrus related to word repetition effects: LORETA imaging with 128-channel EEG and individual MRI.
We investigated the brain substrate of word repetition effects on the implicit memory task using low-resolution electromagnetic tomography (LORETA) with high-density 128-channel EEG and individual MRI as a realistic head model. Thirteen right-handed, healthy subjects performed a word/non-word discrimination task, in which the words and non-words were presented visually, and some of the words appeared twice with a lag of one or five items. All of the subjects exhibited word repetition effects with respect to the behavioral data, in which a faster reaction time was observed to the repeated word (old word) than to the first presentation of the word (new word). The old words elicited more positive-going potentials than the new words, beginning at 200 ms and lasting until 500 ms post-stimulus. We conducted source reconstruction using LORETA at a latency of 400 ms with the peak mean global field potentials and used statistical parametric mapping for the statistical analysis. We found that the source elicited by the old words exhibited a statistically significant current density reduction in the left inferior frontal gyrus. This is the first study to investigate the generators of word repetition effects using voxel-by-voxel statistical mapping of the current density with individual MRI and high-density EEG.


Stacked bilayer phosphorene: strain-induced quantum spin Hall state and optical measurement.
Bilayer phosphorene attracted considerable interest, giving a potential application in nanoelectronics owing to its natural bandgap and high carrier mobility. However, very little is known regarding the possible usefulness in spintronics as a quantum spin Hall (QSH) state of material characterized by a bulk energy gap and gapless spin-filtered edge states. Here, we report a strain-induced topological phase transition from normal to QSH state in bilayer phosphorene, accompanied by band-inversion that changes number from 0 to 1, which is highly dependent on interlayer stacking. When the bottom layer is shifted by 1/2 unit-cell along zigzag/armchair direction with respect to the top layer, the maximum topological bandgap 92.5 meV is sufficiently large to realize QSH effect even at room-temperature. An optical measurement of QSH effect is therefore suggested in view of the wide optical absorption spectrum extending to far infra-red, making bilayer phosphorene a promising candidate for opto-spintronic devices.


Saline magnetic resonance arthrography in the evaluation of glenohumeral instability.
Sixty-five patients underwent magnetic resonance (MR) shoulder arthrography. Forty-eight of these patients underwent examination under anesthesia (EUA). MR images were retrospectively evaluated for signs felt to be imaging indicators of shoulder instability, including evaluation of various capsular measurements and the presence of glenoid labral tears, as well as Hill-Sachs fractures. Statistical analysis of the results showed that no correlation between capsular indicators with EUA-documented instability was found. However, there was a statistically significant correlation between the presence of a Bankart cartilaginous deformity (p = 0.000) and Hill-Sachs fractures (p = 0.022) with EUA-documented instability. Sensitivity to labral tears was 89% and specificity was 98%, whereas Hill-Sachs fracture detection was 69% and 87%, respectively. We believe that MR saline arthrography is of benefit in the evaluation of the anterior labrum when unenhanced MR imaging is inconclusive, and we speculate on the role of MR arthrography as a primary investigative tool.


Quality of Relationships With Caregivers, Depression, and Life Satisfaction After Dysvascular Lower Extremity Amputation.
To describe the relationship between caregiver-specific support and conflict, and psychosocial outcomes among individuals experiencing their first dysvascular lower extremity amputation (LEA). Cross-sectional cohort study using self-report surveys. Department of Veterans Affairs, academic medical center, and level I trauma center. Individuals undergoing their first major LEA because of complications of peripheral arterial disease (PAD) or diabetes who have a caregiver and completed measures of caregiver support and conflict (N=137; 94.9% men). Not applicable. The Patient Health Questionnaire-9 to assess depression and the Satisfaction With Life Scale to assess life satisfaction. In multiple regression analyses, controlling for global levels of perceived support, self-rated health, age, and mobility, caregiver-specific support was found to be associated with higher levels of life satisfaction and caregiver-specific conflict was found to be associated with lower levels of life satisfaction and higher levels of depressive symptoms. The specific relationship between individuals with limb loss and their caregivers may be an important determinant of well-being. Conflict with caregivers, which has received little attention thus far in the limb loss literature, appears to play a particularly important role. Individuals with limb loss may benefit from interventions with their caregivers that both enhance support and reduce conflict.


The murine Ten-m/Odz genes show distinct but overlapping expression patterns during development and in adult brain.
The mouse TEN-M/ODZ proteins belong to a new family of type II transmembrane proteins with unknown function. The family consists of four members, which are expressed highly in brain and less in many other tissues. In the present study we have generated specific RNA probes and antibodies to characterize the expression of the 4 Ten-m/Odz genes in the developing and adult central nervous system (CNS) of mice. Ten-m/Odz3 and Ten-m/Odz4 mRNAs were first detectable at E7.5, Ten-m/Odz2 expression started at the 37 somite (E 10.5) stage, while Ten-m/Odz1 mRNA is not found before E15.5. In the adult mouse CNS mRNAs of the 4 Ten-m/Odzs were expressed in distinct patterns, which partially overlapped. Immunostaining and in situ hybridization localized proteins and mRNAs of Ten-m/Odzs in adjacent areas suggesting that TEN-M/ODZ proteins might be transported from the cell body along the axon or that they are shed from the cell surface and diffuse into distant regions.


Clonotypic analysis of T cells infiltrating the skin of patients with atopic dermatitis: evidence for antigen-driven accumulation of T cells.
Atopic dermatitis (AD) is a chronic inflammation of the skin characterized by marked infiltration of lymphocytes, suggesting an important role for cellular immune responses in the pathogenesis of AD. It is still unclear, however, whether accumulation of lymphocytes results from antigen-driven mechanisms or by nonspecific inflammatory processes. We applied a novel method of T cell clonotypic analysis, using a combination of reverse transcriptase-PCR with multiple T cell receptor (TCR) primers and subsequent single-strand conformation polymorphism (SSCP). Using this method, we were able to detect oligoclonal accumulation of T cells in inflamed skin areas of patients with AD, but not in normal skin. Identical T cell clones with the same antigen specificities were present in samples obtained from separate skin regions. Our results indicate that antigen(s) that exist in large areas of the skin stimulate and expand a relatively restricted number of antigen-specific T cells, leading to oligoclonal accumulation of T cells. We suggest that a marked antigen-driven infiltration of T cells is present in AD.


The current state of GMO governance: are we ready for GM animals?
Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology.


Transesterification of soybean oil using combusted oyster shell waste as a catalyst.
Transesterification of soybean oil catalyzed by combusted oyster shell, which is waste material from shellfish farms, was examined. Powdered oyster shell combusted at a temperature above 700 degrees C, at which point the calcium carbonate of oyster shell transformed to calcium oxide, acted as a catalyst in the transesterification of soybean oil. On the basis of factorial design, the reaction conditions of catalyst concentration and reaction time were optimized in terms of the fatty acid methyl ester concentration expressed as biodiesel purity. Under the optimized reaction conditions of a catalyst concentration and reaction time of 25wt.%. and 5h, respectively, the biodiesel yield, expressed relative to the amount of soybean oil poured into the reaction vial, was more than 70% with high biodiesel purity. These results indicate oyster shell waste combusted at high temperature can be reused in biodiesel production as a catalyst.


The isolation and genetic characterization of extrachromosomal chloramphenicol and oligomycin-resistant mutants from the petite-negative yeast Kluyveromyces lactis.
Spontaneous mutants of the petite-negative yeast Kluyveromyces lactis, resistant to the antibiotics chloramphenicol and oligomycin, were isolated and genetically characterized. Three chloramphenicol-resistant mutants showed non-Mendelian inheritance when crossed to sensitive parents. Of 5 oligomycin-resistant strains studied, three exhibited resistance due to the presence of an extrachromosomal mutation. The resistance of the other two deriving from a nuclear and recessive mutation. When two factor crosses in trans configuration were performed between two of the chloramphenicol and the five oligomycin-resistant mutants a polarity in recombination was observed with a predominance of sensitive (OSCS) over resistant (ORCR) reciprocal recombinants. Allelism tests carried out among the oligomycin-resistant mutants indicated the presence of at least two distinct extrachromosomal regions responsible for the resistance.


Type 1 copper site synthetic model complexes with increased redox potentials.
Reactions of NaSCPh(3) with (R(3)tacn)Cu(OTf)(2) (R is Me, iPr; tacn is 1,4,7-triazacyclononane; OTf is CF(3)SO(3)(-)) yield blue complexes identified as ((R(3)tacn)CuSCPh(3))(OTf) on the basis of UV-vis, resonance Raman, and electron paramagnetic resonance (EPR) spectroscopy and electrospray ionization mass spectrometry. These complexes exhibit spectroscopic properties typical of type 1 copper sites in proteins, including diagnostic Sπ → Cu(d(x(2)-y(2))) ligand-to-metal charge transfer transitions at approximately 610-630 nm and small A(||) values in EPR spectra of less than 100 × 10(-4) cm(-1). Cyclic voltammetry experiments revealed redox potentials for the complexes similar to those of several low-potential type 1 copper proteins (e.g., azurin, stellacyanin) and approximately 0.5 V higher than those of previously reported model compounds. Thus, the new complexes mimic key aspects of both the structure and the function of type 1 copper sites.


Higher dietary fiber intake associated with better survival in male but not female cancer patients: Evidence from National Health and Nutrition Examination Survey 1999-2014.
Recent studies have found that dietary fiber improves prognosis in cancer patients. However, few subgroup analyses exist. Subgroups can differ greatly in terms of different factors such as dietary intake, lifestyle, and sex. It is unclear whether fiber benefits all of the subgroups equally. In this study, we examined differences in dietary fiber consumption and cancer mortality between subgroups, including sex. This trial was conducted using eight consecutive National Health and Nutrition Examination Surveys (NHANESs) cycles data between 1999 and 2014. Subgroup analyses were used to investigate the results and heterogeneity within subgroups. Survival analysis was performed using the Cox proportional hazard model and Kaplan-Meier curves. Multivariable Cox regression models and restricted cubic spline analysis were applied to examine the association between dietary fiber intake and mortality. In total, 3504 cases were included in this study. Among the participants, the mean age (SD) was 65.5 (15.7) y and 1657 (47.3%) of the participants were men. Subgroup analysis found that men differed significantly from women (P for interaction < 0.001). We found no significant differences in the other subgroups (all P for interaction > 0.05). During an average follow-up of 6.8 y, 342 cancer deaths were recorded. The Cox regression models found that fiber consumption was associated with a lower cancer mortality rate in men (model I: hazard ratio [HR] = 0.60; 95% CI, 0.50-0.72; model II: HR = 0.60; 95% CI, 0.47-0.75; and model III: HR = 0.61; 95% CI, 0.48-0.77). However, there was no relationship between fiber consumption and cancer mortality in women (model I: HR = 1.06; 95% CI, 0.88-1.28; model II: HR = 1.03; 95% CI, 0.84-1.26; and model III: HR = 1.04; 95% CI, 0.87-1.50). The Kaplan-Meier curve illustrates that male patients who consumed higher levels of dietary fiber survived significantly longer than those who consumed lower levels of fiber (P < 0.001). However, there were no significant differences between the two groups in terms of female patients (P = 0.84). A dose-response analysis found an L-shaped relationship between fiber intake and mortality among men. This study found that higher dietary fiber intake was only associated with better survival in male cancer patients, not in female cancer patients. Sex differences between dietary fiber intake and cancer mortality were observed.


Schisantherin A protects against 6-OHDA-induced dopaminergic neuron damage in zebrafish and cytotoxicity in SH-SY5Y cells through the ROS/NO and AKT/GSK3β pathways.
The fruit of Schisandra chinensis (Turcz.) Baill, has been traditionally used in management of liver diseases and ageing associated neurodegeneration. The bioactive compound from this medicinal plant would be valuable for its potential use in prevention and treatment of Parkinson׳s disease. The overall objective of the present study was to understand the neuroprotective effect of schisantherin A, a dibenzocyclooctadiene lignan from the fruit of S. chinensis (Turcz.) Baill, and to elucidate its underlying mechanism of action. This study investigated the protective effect of schisantherin A against selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA)-induced neural damage in human neuroblastoma SH-SY5Y cells and zebrafish models. Oxidative stress and related signaling pathways underlying the neuroprotective effect were determined by multiple biochemical assays and Western blot. Pretreatment with schisantherin A offered neuroprotection against 6-OHDA-induced SH-SY5Y cytotoxicity. Moreover, schisantherin A could prevent 6-OHDA-stimulated dopaminergic neuron loss in zebrafish. Our mechanistic study showed that schisantherin A can regulate intracellular ROS accumulation, and inhibit NO overproduction by down-regulating the over-expression of iNOS in 6-OHDA treated SH-SY5Y cells. Schisantherin A also protects against 6-OHDA-mediated activation of MAPKs, PI3K/Akt and GSK3β. These findings demonstrate that schisantherin A may have potential therapeutic value for neurodegenerative diseases associated with abnormal oxidative stress such as Parkinson׳s disease.


Variations in plasma apolipoprotein C-III levels are strong correlates of the triglyceride response to a high-monounsaturated fatty acid diet and a high-carbohydrate diet.
The objective of this study was to examine how a diet rich in carbohydrates (high-CHO) vs a diet rich in monounsaturated fatty acids (high MUFA) consumed ad libitum modulated plasma apolipoprotein C-III (apo C-III) levels and to examine the extent to which diet-induced changes in plasma apo C-III were associated with concurrent variations in plasma triglyceride (TG) levels. Forty-seven men (mean age, 35.7 +/- 11.4 years; body mass index, 29.0 +/- 5.1 kg/m2) were randomly assigned to either a high-CHO diet (CHO, 58%; fat, 26%; n = 23) or a high-MUFA diet (CHO, 45%; fat, 40%; MUFA, 22.5%; n = 24), which they consumed for 6 to 7 weeks. Fasting and postprandial lipemia after an oral fat load and fasting plasma apo C-III were measured at the beginning and at the end of the dietary intervention. Ad libitum consumption of the high-CHO diet induced a significant reduction in body weight (-2.6%, P < .0001), but had no impact on plasma apo C-III concentrations and on fasting and postprandial plasma TG levels. In contrast, ad libitum consumption of the high-MUFA diet also resulted in a significant reduction in body weight (-2.3%, P < .01) as well as in significant reductions in plasma apo C-III (-11%, P = .05) and fasting plasma TG (-17%, P < .01). Diet-induced variations in plasma apo C-III concentrations were correlated with changes in fasting and postprandial TG levels both in the high-CHO (r > 0.70, P < .001) and the high-MUFA groups (r > 0.42, P < .05). These results indicate that variations in plasma apo C-III levels are strong correlates of the fasting and postprandial plasma TG responses to high-MUFA and high-CHO diets.


EUS pancreatic function testing and dynamic pancreatic duct evaluation for the diagnosis of exocrine pancreatic insufficiency and chronic pancreatitis.
EUS and endoscopic pancreatic function tests (ePFTs) may be used to diagnose minimal-change chronic pancreatitis (MCCP). The impact of evaluation for exocrine pancreatic insufficiency (EPI) and real-time assessment of EUS changes after intravenous secretin on the clinical diagnosis of MCCP is unknown. Patients with suspected MCCP underwent baseline EUS assessment of the pancreatic parenchyma and measurement of the main pancreatic duct (B-MPD) in the head, body, and tail. Human secretin 0.2 μg/kg was given intravenously followed 4, 8, and 12 minutes later by repeat MPD (S-MPD) measurements. Duodenal samples at 15, 30, and 45 minutes were aspirated to assess bicarbonate concentration. Endoscopists rated the percentage clinical likelihood of chronic pancreatitis (1) before secretin; (2) after secretin but before aspiration; and (3) after bicarbonate results. A total of 145 consecutive patients (mean age, 44±13 years; 98 females) were diagnosed with EPI (n = 32; 22%) or normal exocrine pancreatic function (n = 131, 78%). S-MPD/B-MPD ratios in the tail 4 and 8 minutes after secretin were higher in the group with normal exocrine function. Ratios at other times, locations, and duodenal fluid volumes were similar between the 2 groups. A statistically significant change in the median percentage likelihood of chronic pancreatitis was noted after secretin in all groups. The sensitivity and specificity of EPI for the EUS diagnosis of chronic pancreatitis (≥5 criteria) were 23.4% (95% confidence interval, 12.3-38.0) and 78.6% (95% confidence interval, 69.1-86.2), respectively. Real-time EUS findings and ePFTs have a significant impact on the clinical assessment of MCCP. The diagnosis of EPI shows poor correlation with the EUS diagnosis of MCCP. (Clinical trial registration number: NCT01997476.).


Tracking fetal development through molecular analysis of maternal biofluids.
Current monitoring of fetal development includes fetal ultrasonography, chorionic villus sampling or amniocentesis for chromosome analysis, and maternal serum biochemical screening for analytes associated with aneuploidy and open neural tube defects. Over the last 15 years, significant advances in noninvasive prenatal diagnosis (NIPD) via cell-free fetal (cff) nucleic acids in maternal plasma have resulted in the ability to determine fetal sex, RhD genotype, and aneuploidy. Cff nucleic acids in the maternal circulation originate primarily from the placenta. This contrasts with cff nucleic acids in amniotic fluid, which derive from the fetus, and are present in significantly higher concentrations than in maternal blood. The fetal origin of cff nucleic acids in the amniotic fluid permits the acquisition of real-time information about fetal development and gene expression. This review seeks to provide a comprehensive summary of the molecular analysis of cff nucleic acids in maternal biofluids to elucidate mechanisms of fetal development, physiology, and pathology. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.