Deep learning forecasting using time-varying parameters of the SIRD model for Covid-19.
Accurate epidemiological models are necessary for governments, organizations, and individuals to respond appropriately to the ongoing novel coronavirus pandemic. One informative metric epidemiological models provide is the basic reproduction number ([Formula: see text]), which can describe if the infected population is growing ([Formula: see text]) or shrinking ([Formula: see text]). We introduce a novel algorithm that incorporates the susceptible-infected-recovered-dead model (SIRD model) with the long short-term memory (LSTM) neural network that allows for real-time forecasting and time-dependent parameter estimates, including the contact rate, [Formula: see text], and deceased rate, [Formula: see text]. With an accurate prediction of [Formula: see text] and [Formula: see text], we can directly derive [Formula: see text], and find a numerical solution of compartmental models, such as the SIR-type models. Incorporating the epidemiological model dynamics of the SIRD model into the LSTM network, the new algorithm improves forecasting accuracy. Furthermore, we utilize mobility data from cellphones and positive test rate in our prediction model, and we also present a vaccination model. Leveraging mobility and vaccination schedule is important for capturing behavioral changes by individuals in response to the pandemic as well as policymakers.


Limb lengthening using ankle joint distraction (arthrodiastasis) followed by arthrodesis. Experience with one case.
Tibial aplasias are difficult entities to manage and sometimes require significant limb lengthening. Preserving the joint is the preferred option in these cases. However, when function is not ensured, lengthening beginning in the joint can be attempted followed by arthrodesis. This report presents the clinical and radiological results of a patient treated with intra-articular lengthening (or arthrodiastasis) associated with talocrural arthrodesis. Although this original technique provided satisfactory results, this surgical program remains complicated.


Opioid-related emergencies in New York City after the Great Recession.
The rise in opioid-related mortality and opioid-related emergency department (ED) visits has stimulated research on whether broader economic declines, such as the Great Recession, affect opioid-related morbidity. We examine in New York City whether one measure of morbidity-opioid-related ED visits-responded acutely to the large negative "shock" of the Great Recession. Data comprise outpatient "treat and release" opioid-related ED visits in New York City for the 72 months spanning January 2006 to December 2011, taken from the Statewide Emergency Department Database (n = 150,246). We modeled the monthly incidence of opioid-related ED visits using Autoregressive, Integrated, Moving Average (ARIMA) time-series methods to control for patterning in ED visits before examining its potential association with the economic shock of the Great Recession. New York City shows a mean of 1761 outpatient ED visits per month for opioid dependence and abuse. Unexpectedly large drops in employment coincide with fewer than expected opioid dependence and abuse ED visits in that same month. The result (coefficient = 0.046, 95% Confidence Interval [CI]: 0.002, 0.090) represents a 0.8% drop in overall incidence of opioid dependence and abuse ED visits during the Great Recession. We, however, observe no association between the Great Recession and ED visits for prescription opioid overdose or heroin overdose, or with inpatient ED visits for opioid dependence and abuse. Findings, if replicated, indicate distinct short-term reductions in opioid-related morbidity following the Great Recession. This result diverges from previous findings of increased opioid use following extended economic downturns.


Evaluation of the efficacy of pro-yellow laser in the management of vascular skin disorders.
Lasers have great importance in the management of vascular skin lesions. To determine the efficacy of 577-nm pro-yellow laser in cure of certain vascular skin diseases. Seventy-four patients who are diagnosed as vascular skin diseases were involved in this study. All participants were treated with 577-nm pro-yellow laser with 4-week intervals. The photographs that were taken before and at every following visit were used to evaluate improvement. A significant improvement occurred in port-wine stain, rosacea, facial telangiectasia, venous lake, scrotal angiokeratoma, and cherry angioma cases. Vascular skin lesions can be treated with 577-nm pro-yellow laser with a minimal adverse effect and great success rate.


The diumycin complex. Comparative studies on antibiotics from diumycin-and macarbomycin-fermentations.
Six phosphorus-containing antibiotics were isolated from both diumycin and macarbomycin fermentation products. On the basis of their chromatographic behavior and of their physico-chemical and microbiological properties it can be assumed that not only the main component but also the five minor components are the same in both antibiotic complexes. A comparison of the six components with the known classifications of diumycins and macarbomycins was made.


Blocking of primary in vitro antibody responses to thymus-independent and thymus-dependent antigens with antiserum specific for IgM or IgD.
The effect of anti-mu and anti-delta on the primary in vitro IgM response of murine splenocytes to thymus-dependent (trinitrophenylated erythrocytes) and thymus-independent (trinitrophenylated brucella) forms of trinitrophenyl was studied. The results indicate that either anti-mu or anti-delta can block the response of adult splenocytes to the thymus-dependent antigen. The thymus-dependent responses of neonatal splenocytes that bear a low concentration of IgD were also abrogated by treatment with anti-delta. In contrast, anti-mu, but not anti-delta, blocked the response of adult splenocytes to the thymus-independent antigen used. These results indicate that both IgM and IgD are receptors required for triggering cells by a thymus-dependent antigen but that only IgM receptors are required for triggering by the thymus-independent antigen used.


Dissemination of NDM-producing bacteria in Southern Brazil.
The dissemination of NDM-1 carbapenemases (New Delhi Metallo-β-lactamase) is a global public health problem, mainly in developing countries. The aim of this study was to characterize the spread of NDM-producing bacteria in the Southern Brazilian states analyzing epidemiological, molecular, and antimicrobial susceptibility aspects. A total of 10,684 carbapenem-resistant isolates of Enterobacterales, Pseudomonas spp. and Acinetobacter spp. obtained from several hospitals in eight cities in Southern Brazil were screened, and 486 NDM-producing bacteria were selected. The incidence varied from 0.5 to 77 cases/100.000 habitants. ST11, ST15, ST340 and ST674 were the most common in K. pneumoniae. A total of 5 plasmids were identified in one K. pneumoniae strain: Col440I, Col440II, IncFIA(HI1), IncFIB(K), IncFIB(pQil)/ IncFII(K), and IncR. The number of patients with NDM-producing bacteria has increased in Southern Brazil, whose gene is present in different plasmids, explaining the expansion of this enzyme.


A Systematic Review of the Roles and Contributions of Peer Providers in the Behavioral Health Workforce.
Peer providers with lived experiences of mental health and substance use are a growing component of the workforce responsible for the prevention and treatment of behavioral health disorders. This systematic literature review aims to better define the roles of peers and their unique contributions to behavioral health care. Researchers searched MEDLINE, CINAHL Complete, PsycINFO, Cochrane Central, and Scopus databases for studies published between January 1, 2013 and April 3, 2020. Studies were included if they (1) were experimental or observational studies, (2) included an adult population of people with a behavioral health disorder, and (3) used paid peer providers in addition to traditional behavioral health services. Researchers extracted sample demographics, intervention characteristics, outcome data, and significant associations from studies that met inclusion criteria and assessed the trends in these data in May 2020. A total of 23 articles assessing peer-provided services were included. Peers were employed most frequently in mental healthcare roles in the Department of Veterans Affairs, hospital, and community health facilities. A total of 14 studies observed significant clinical improvements in participants' social functioning, quality of life, patient activation, and behavioral health. A majority of studies involved the supervision of peers and required peers to have completed training in service delivery. Peers are effective providers of behavioral health treatment and relapse prevention services who encourage recovery through resilience building, empowerment, and self-advocacy. There remains a need for more evidence-based interventions on the efficacy of peers in substance use disorder treatment and the impact of formalized certification and training opportunities.


Disruption of Growth Hormone Receptor in Adipocytes Improves Insulin Sensitivity and Lifespan in Mice.
Growth hormone receptor knockout (GHRKO) mice have been used for 25 years to uncover some of the many actions of growth hormone (GH). Since they are extremely long-lived with enhanced insulin sensitivity and protected from multiple age-related diseases, they are often used to study healthy aging. To determine the effect that adipose tissue has on the GHRKO phenotype, our laboratory recently created and characterized adipocyte-specific GHRKO (AdGHRKO) mice, which have increased adiposity but appear healthy with enhanced insulin sensitivity. To test the hypothesis that removal of GH action in adipocytes might partially replicate the increased lifespan and healthspan observed in global GHRKO mice, we assessed adiposity, cytokines/adipokines, glucose homeostasis, frailty, and lifespan in aging AdGHRKO mice of both sexes. Our results show that disrupting the GH receptor gene in adipocytes improved insulin sensitivity at advanced age and increased lifespan in male AdGHRKO mice. AdGHRKO mice also exhibited increased fat mass, reduced circulating levels of insulin, c-peptide, adiponectin, resistin, and improved frailty scores with increased grip strength at advanced ages. Comparison of published mean lifespan data from GHRKO mice to that from AdGHRKO and muscle-specific GHRKO mice suggests that approximately 23% of lifespan extension in male GHRKO is due to GHR disruption in adipocytes vs approximately 19% in muscle. Females benefited less from GHR disruption in these 2 tissues with approximately 19% and approximately 0%, respectively. These data indicate that removal of GH's action, even in a single tissue, is sufficient for observable health benefits that promote long-term health, reduce frailty, and increase longevity.


Esthetic restorative options for pulpotomized primary molars: a review of literature.
The goal of this manuscript was to review the existing literature in regards to esthetic options to restore pulpotomized primary molars. A pubmed literature search has been performed and all relevant studies were assessed. Two laboratory, 3 restrospective and 4 prospective clinical studies were found, reviewed and analyzed. Based on the limited information available, we concluded that tooth colored and bonded restorations showed promising results as alternative materials to replace stainless steel crowns after pulpotomies in primary molars. Hybrid composites tend to perform better than compomers. Resin modified glass ionomer cements demonstrated excellent marginal seal and retention. More long-term follow up studies are necessary until more definitive recommendations can be made.


Biological Implications and Clinical Potential of Metastasis-Related miRNA in Colorectal Cancer.
Colorectal cancer (CRC), ranking as the third commonest cancer, leads to extremely high rates of mortality. Metastasis is the major cause of poor outcome in CRC. When metastasis occurs, 5-year survival rates of patients decrease sharply, and strategies to enhance a patient's lifetime seem limited. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that are significantly involved in manipulation of CRC malignant phenotypes, including proliferation, invasion, and metastasis. To date, accumulating studies have revealed the mechanisms and functions of certain miRNAs in CRC metastasis. However, there is no systematic discussion about the biological implications and clinical potential (diagnostic role, prognostic role, and targeted therapy potential) of metastasis-related miRNAs in CRC. This review mainly summarizes the recent advances of miRNA-mediated metastasis in CRC. We also discuss the clinical values of metastasis-related miRNAs as potential biomarkers or therapeutic targets in CRC. Moreover, we envisage the future orientation and challenges in translating these findings into clinical applications.


Respect for cultural diversity in bioethics. Empirical, conceptual and normative constraints.
In contemporary debates about the nature of bioethics there is a widespread view that bioethical decision making should involve certain knowledge of and respect for cultural diversity of persons to be affected. The aim of this article is to show that this view is untenable and misleading. It is argued that introducing the idea of respect for cultural diversity into bioethics encounters a series of conceptual and empirical constraints. While acknowledging that cultural diversity is something that decision makers in bioethical contexts should try to understand and, when possible, respect, it is argued that this cultural turn ignores the typically normative role of bioethics and thus threatens to undermine its very foundations.


Neuronal morphology enhances robustness to perturbations of channel densities.
Biological neurons show significant cell-to-cell variability but have the striking ability to maintain their key firing properties in the face of unpredictable perturbations and stochastic noise. Using a population of multi-compartment models consisting of soma, neurites, and axon for the lateral pyloric neuron in the crab stomatogastric ganglion, we explore how rebound bursting is preserved when the 14 channel conductances in each model are all randomly varied. The coupling between the axon and other compartments is critical for the ability of the axon to spike during bursts and consequently determines the set of successful solutions. When the coupling deviates from a biologically realistic range, the neuronal tolerance of conductance variations is lessened. Thus, the gross morphological features of these neurons enhance their robustness to perturbations of channel densities and expand the space of individual variability that can maintain a desired output pattern.


Case Report: Successful Anterior Circulation Thrombectomy After 24 Hours in an Adolescent.
Arterial ischemic stroke in children comes with the potential for morbidity and mortality and can result in high cost of care and decreased quality of life among survivors. Children with arterial ischemic stroke are increasingly being treated with mechanical thrombectomy, but little is known about the risks and benefits 24 hours after a patient's last known well (LKW) time. A 16-year-old female presented with acute onset of dysarthria and right hemiparesis with LKW time 22 hours prior. Pediatric National Institutes of Health Stroke Scale score was 12. Magnetic resonance imaging showed diffusion restriction and T2 hyperintensity primarily in the left basal ganglia. Magnetic resonance angiography revealed left M1 occlusion. Arterial spin labeling showed a large apparent perfusion deficit. She underwent thrombectomy with TICI3 recanalization 29.5 hours after LKW time. At 2-month follow-up, her examination showed moderate right-hand weakness and mild diminished sensation of the right arm. Adult thrombectomy trials include patients up to 24 hours from their LKW time and suggest that some patients maintain a favorable perfusion profile for over 24 hours. Without intervention many go on to experience infarct expansion. The persistence of a favorable perfusion profile likely reflects robust collateral circulation. We hypothesized our patient was relying on collateral circulation to maintain the noninfarcted areas of her left middle cerebral artery territory. Owing to concern for eventual collateral failure, thrombectomy outside of the 24-hour window was performed. This case serves as a call to action to better understand the impact of collateral circulation on cerebral perfusion in children with large vessel occlusions and delineate which children may benefit from thrombectomy in a delayed time window.


Scale for chemotherapy-induced long-term neurotoxicity (SCIN): psychometrics, validation, and findings in a large sample of testicular cancer survivors.
Neurotoxicity is common after modern chemotherapy, and can be assessed both objectively and subjectively based on symptoms reported by patients. The aim of this study was to explore the psychometric properties of a brief self-report scale for chemotherapy induced long-term neurotoxicity (the SCIN). As part of a questionnaire survey 684 testicular cancer survivors (TCSs) filled in the SCIN, which assesses peripheral sensory neuropathy (paresthesias), Raynaud's phenomenon, and ototoxicity. Factor structure and internal consistency reliability of the SCIN were tested by the split-half method. In 538 TCSs, audiogram data were compared to the patients SCIN ratings of hearing. The internal consistency of the SCIN showed a Cronbach's alpha of 0.72. The three-factor structure of the SCIN was confirmed with 77% explained variance. All the SCIN items discriminated significantly between the TCSs who had been treated with cisplatin-based chemotherapy vs. those who did not receive such treatment. The individual cumulative cisplatin dose correlated significantly with all the SCIN items. The Pearson product-moment correlation coefficient was 0.54 between hearing reduction at 4000 Hertz measured by audiogram and the SCIN self-report of reduced hearing. The SCIN shows good psychometric properties, and is recommended as a brief screening instrument for chemotheraphy-indeed neurotoxicity.


Assessment of temporomandibular and cervical spine disorders in tinnitus patients.
In treating patients with temporomandibular joint (TMJ) dysfunction it was noticed that tinnitus and vertigo were common in such patients and there was also muscular tension in jaw and neck. During treatment of these patients it was also noted that injection of lidocaine in a jaw muscle (m. pt. lat.) reduced not only their muscular problems but also that the tinnitus was reduced while the local anesthetic was active. Evaluation of 39 patients with disabling tinnitus, and all suffered from tinnitus, revealed that 10 of them had bilateral tinnitus and TMJ disorders revealed that pain in the face, temples or jaw occurred often among these patients. Many of such patients had also symptoms of cervical spine disorders, head, neck and shoulder pain, and limitations in side bending and rotation were also frequent complaints. One-third of these patients could influence tinnitus by jaw movements and 75% could trigger vertigo by head or neck movements. Treatment of jaw and neck disorders in 24 patients with Ménière's disease had a beneficial effect on not only their episodic vertigo but also on their tinnitus and aural fullness. At the 3-year follow-up, intensity of all symptoms were significantly reduced (p<0.001).


Anterior C2-3 fusion surgery alone for highly displaced Hangman's fracture with severe angulation of C2-3 of more than 30°.
Highly displaced Hangman's fracture is a very rare and extremely unstable fracture of the C2 axis. Combined anteroposterior or posterior long-segment fusion surgery is typically performed for the treatment of highly displaced Hangman's fracture. However, these kinds of surgeries increase the risk of complications, loss of motion, and hospital costs. We sought to investigate the surgical outcomes of anterior C2-3 fusion surgery alone for highly displaced Hangman's fractures with severe angulation of C2-3 by more than 30° and discoligamentous injury. A total of five patients (four men and one woman) were included in this study with a mean age of 40.4 years (range, 26-70 years). The mean follow-up period after surgery was 37.2 months (range, 12-96 months). The fracture characteristics, treatment methods, and outcomes were retrospectively analyzed. All five patients had type II Hangman's fractures (according to the Levine and Edwards classification scheme). None of the included patients had neurologic deficit or other spine injury but all patients had complete C2-3 discoligamentous injury. Before surgery, all patients successfully achieved closed reduction by skull traction, followed by C2-3 anterior decompression and fusion (ACDF) with plating. For interbody grafting, three patients received a polyetheretherketone (PEEK) cage filled with an autogenous cancellous iliac bone graft and two received autogenous tricortical iliac bone grafts. Severe angulation (39.2° vs. 3.0°, P < 0.001) and severe displacement (76.1% vs. 4.0%, P < 0.001) of C2-3 were both significantly corrected after surgery. All patients had achieved solid fusion at last follow-up. In terms of clinical outcomes, the mean neck pain visual analog scale score was significantly improved (8.6 points vs. 1.8 points, P < 0.001). The mean neck disability index value was also significantly improved (45.4 points vs. 13.0 points, P < 0.01). According to Odom's criteria, all patients achieved satisfactory outcomes. No major complications occurred. One patient complained of dysphagia, but recovered after three months with conservative treatment. Preoperative closed reduction and anterior C2-3 fusion surgery alone should be considered as a less-invasive and useful surgical option for highly displaced Hangman's fracture with severe angulation of C2-3, which is an extremely unstable fracture of the C2 axis.


A chemical approach to the mechanism of B-lymphocyte activation. II. The pure presentation of haptens does not inactivate B lymphocytes.
Dinitrophenyl (DNP)-lysine-polymethylmethacrylate and DNP-cellulose conjugates do not irreversibly inactivate anti-DNP antigen-sensitive cells, regardless of the dose (up to 10 mg) or persistence of the stimulation (up to 2 weeks). Since these conjugates constitute pure hapten presentations, it is concluded that the pure hapten presentation to B lymphocyte does not irreversibly inactivate them. When murine spleen cells are cultured with Escherichia coli lipopolysaccharide (LPS) and (non-immunogenic) DNP-lysine-polymethylmethacrylate or (non-immunogenic) DNP-cellulose conjugates, an anti-DNP immune response occurs. However, replacement of DNP-lysine-polymethylmethacrylate with polymethylmethacrylate, or DNP-cellulose with cellulose, also results in a similar anti-DNP response. It is consequently concluded that the anti-DNP responses are entirely elicited by LPS, the hapten Dnp being inoperative. The anti-DNP response elicited by DNP-Ficoll is, upon exhaustive testing, carrier-dependent. This implies that the mechanism of DNP-Ficoll immunogenicity is not two cooperative signals passed on to B lymphocytes via the hapten DNP. These results argue against any two-signal model of B-lymphocyte activation.


Echogenicity of liver metastases from colorectal carcinoma is an independent prognostic factor in patients treated with regional chemotherapy.
Echogenicity of liver metastases was found to be a predictive biologic factor influencing long-term outcome after curative liver resection. The current analysis focuses on the influence of echogenicity on survival in patients treated with intraarterial chemotherapy for unresectable colorectal carcinoma liver metastases. A retrospective analysis of prospectively collected data at the Department of Surgery at the University of New South Wales-affiliated St. George Hospital was performed. Two hundred twelve consecutive patients with unresectable hepatic metastases from colorectal carcinoma treated between May 1992 and September 2000 were analyzed. Echogenicity of metastases was measured intraoperatively using a 5 MHz probe. Overall survival difference was compared between hyper- and hypoechoic metastases on an intention-to-treat basis. At a median followup of 15.1 months, 47 patients (22%) were alive and 165 (78%) had died. A significant survival benefit was observed in patients having hyperechoic lesions (median survival 16.2 months, 95% confidence interval [CI] 13.9-18.5) compared to hypoechoic lesions (median survival 11.6 months, 95% CI 8-15.2), P < 0.01. Other prognostic factors were differentiation of the primary tumor (P < 0.02), percentage hepatic replacement (P < 0.05) and carcinoembryonic antigen decrease (P < 0.03). Echogenicity was identified as an independent prognostic factor in multivariate analysis (P < 0.009). Echogenicity is an important prognostic survival parameter.


Total ankle replacement: a historical perspective.
In the early 1970s, total ankle replacement was criticized because of poor outcomes with initial implant designs. Modifications were made that lead to the development of several generations of implants. The early shortcomings gave researchers and surgeons the impetus to improve implant designs and surgical technique. Total ankle replacement has become more widely accepted in recent years because of improved design and survivorship rates for the implants, as well as improved patient satisfaction scores. Indications for total ankle replacement have broadened. To continue these successes, it is important for surgeons to select appropriate patients for this procedure.


Self-reported needs of patients with Parkinson's disease during COVID-19 emergency in Italy.
Because of COVID-19 outbreak, regular clinical services for Parkinson's disease (PD) patients have been suddenly suspended, causing worries, confusion and unexpected needs in such frail population. Here, we reviewed the messages spontaneously sent by patients to an Italian PD clinic during the first two weeks of COVID-19 lockdown (9-21 March 2020), in order to highlight their main needs and then outline appropriate strategies of care for this critical period. One hundred sixty-two messages were analysed. Forty-six percent queried about clinical services; 28% communicated an acute clinical worsening for which a therapeutic change was done in 52% of cases; 17% (those patients with younger age and milder disease) asked about the relationship between PD and COVID-19; 8% informed about an intercurrent event. Our analysis suggests that PD patients' needs during COVID-19 emergency include appropriate and complete information, a timely update on changes in clinical services, and the continuity of care, even in a remote mode. By addressing these issues, acute clinical worsening, complications and subsequent therapeutic changes could be prevented. In this perspective, telecommunication systems and virtual medicine should be implemented.


Water-carbon nexus relationship and interaction mechanism analysis within Beijing-Tianjin-Hebei urban agglomeration.
As the total water resources consumption control and carbon mitigation continuous improvement, the weak water-carbon incorporate management is increasingly exposed. In this study, a water-carbon nexus assessment framework is proposed to analyze the nexus relationship between water consumption and carbon emission, and distinguishes the coupled water-carbon transmission intensity and the transfer paths under regional and industrial scales. According to the practical input-output table, water consumption, and carbon emission information, the framework is applied to Beijing-Tianjin-Hebei urban agglomeration (BTHUA), a population, resource, and trade intensive area of China. Inter-regional/intra-regional water consumption and carbon emission transfer fluxes between sectors, the pairwise ecological relationship, and the water-carbon nexus were analyzed. Results indicated that the water-carbon transfer indexes from Hebei to Beijing and Tianjin were 161.85 kg/m3 and 113.88 kg/m3 in the study period, along with the most water consumption and carbon emission, and the worst water-carbon nexus. From the industrial perspective, electricity and gas supplying industry provided 7.8% and 29.1% of the total carbon transfer in Tianjin and Hebei, as the most key node sectors on the water-carbon nexus in the BTHUA. The research provides valuably supporting the adjustment of the existing urban agglomeration water-carbon nexus management schemes.


Epidural analgesia and vacuum-assisted delivery in primiparous women: maternal and neonatal outcomes.
We aimed to evaluate the effect of epidural analgesia (EA) on maternal and neonatal outcomes. We conducted a retrospective cohort database study on primiparous women who underwent a vacuum-assisted delivery (VAD) trial between 2005 and 2019 at a university-affiliated tertiary medical center. We compared women with and without the standard "one protocol" patient-controlled EA. The primary outcome was VAD failure. Secondary outcomes were maternal and neonatal morbidities. We performed univariate analysis, followed by multivariable logistic regression analysis to control for potential confounders. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. Overall, 7042 primiparous women attempted VAD during the study period; 6238 (88.3%) and 804 (11.7%) women used and did not use EA, respectively. The VAD failure rate was significantly lower among women with than without EA use (2.5% vs. 4.2%, respectively, p < .01). On multivariable analysis, EA use was found to reduce the VAD failure rate (aOR, 0.05; 95% CI [0.01-0.49], p = .01). Notably, EA use was not associated with an increased rate of any maternal or neonatal adverse outcome (aOR, 1.01; 95% CI [0.8-1.27], p = .95 or aOR, 1.14 95% CI [0.89-1.45], p = .3, respectively). EA use in primiparous women is associated with lower rates of VAD failure without an increase in adverse maternal or neonatal outcomes.


Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT.
Mutations in KIT are more frequent in specific melanoma subtypes, and response to KIT inhibition is likely to depend on the identified mutation. A total of 32 patients with metastatic acral or mucosal melanoma were screened for mutations in KIT exons 11, 13 and 17. KIT mutations were found in 38% of mucosal and in 6% of acral melanomas. Three patients were treated with imatinib and one with sorafenib. All four patients responded to treatment, but three have since progressed within the brain. The observed clinical responses support further investigation of KIT inhibitors in metastatic melanoma, selected according to KIT mutation status.


Comparison of differentially expressed genes in the salivary glands of male ticks, Amblyomma americanum and Dermacentor andersoni.
Genes expressed differentially in the salivary glands of unfed and fed male ticks, Amblyomma americanum (L.), were identified, cloned and sequenced, and some were compared with those expressed in the salivary glands of Dermacentor andersoni. Total protein and RNA increased sixfold in the salivary glands of fed male A. americanum, while in fed male D. andersoni salivary glands, RNA increased approximately 3.5 times. Feeding D. andersoni in the presence of females increased total RNA by 25% over those fed in the absence of females. Complementary DNAs were synthesized from RNA obtained from unfed and fed ticks and amplified using RNA arbitrarily primed polymerase chain reaction (RAP-PCR) with three different primers in separate reactions. Differential display showed clear banding differences between the fed and the unfed ticks in A. americanum and D. andersoni. Sixty-one cDNA fragments that appeared to be from differentially expressed genes in A. americanum were isolated, cloned and sequenced. Hybridization reactions with labeled cDNA probes confirmed the differential expression of many of the genes in unfed and fed ticks' salivary glands; however, many of the bands contained more than one fragment and some of the fragments isolated from apparently differential bands were not specific. Sequences for 28 of the cDNA fragments (150-600 nucleotides in length) demonstrated similarity to genes in the databases, but nine of these were similar to sequences of unknown function. Some of the gene fragments identified may be important to tick feeding or tick salivary gland physiology, including a histamine-binding protein, an organic ion transporter, an apoptosis inhibitor, a cathepsin-B-like cysteine protease, proteins involved in gene regulation and several proteins involved in protein synthesis. Cross-hybridization of identified cDNAs from A. americanum with cDNA probes synthesized from D. andersoni total RNA did not show significant similarity between the two species.


Using vegetation correction coefficient to modify a dynamic particulate nutrient loss model for monthly nitrogen and phosphorus load predictions: a case study in a small loess hilly watershed.
Vegetation is an important factor affecting nutrient enrichment ratio in runoff sediments but few studies have been examined in the effects of different vegetation scenarios on the monthly evolutions of particulate nitrogen (N) and phosphorus (P) loss. In this study, a vegetation correction coefficient was innovatively embedded in a dynamic particulate nutrient loss model to evaluate the monthly trends of particulate N and P loss in a small highly erodible watershed. Results indicate that (i) the monthly sediment yield from June to August 2013 accounted for the dominant percentage in this extreme hydrological year, which was consistent with the monthly trends of rainfall erosivity. The largest monthly sediment yield rate under four different vegetation scenarios all occurred in July with the values of 530.56, 258.09, 579.69, and 370.74 t km-2. (ii) Particulate N and P loss from April to September changed significantly under different vegetation scenarios, and they were mainly concentrated in June and July 2013; only the N and P loss loads in July accounted for > 70% of annual load. However, the loads in January, February, March, October, November, and December were considered as zero because there was no erosive rainfall during the above 6 months. (iii) The reduction efficiency of particulate N and P loss by scenario 1 was about 1.7 times higher than scenario 3, which shows that forestland in sediment reduction was stronger than grassland and cropland in Zhifanggou Watershed. Results provide the underlying insights needed to guide vegetation reconstruction and soil conservation planning in loess hilly regions.


Low-Cost 3-D Hydrophone Scanning Tank with MATLAB GUI Control.
The Focused Ultrasound Foundation has developed a low-cost, validated, open-source hydrophone scanner for the spatial characterization of ultrasound transducers. Assembly instructions and a MATLAB control graphical user interface are provided such that the device can be easily replicated for less than $1000 in roughly 40 person-hours. The low-cost scanning tank's performance was compared with data collected with a commercial automated scanning tank. Pressure measurements of a focused transducer and a planar transducer had less than a 10% difference between the two scanning systems. Two-dimensional automated scans (20 × 20 mm at 0.25-mm resolution) took the low-cost scanning tank 45 min compared with the commercial system's 30 min. A reproducibility study found that the low-cost scanner made consistent peak negative pressure measurements as reflected by the low coefficient of variation for both focused (1.88%) and planar (0.98%) transducers. The low-cost scanner described here is a viable alternative for ultrasound laboratories needing efficient, accurate characterization of ultrasound transducers.


Surgical outcomes of pulmonary metastasectomy for head and neck cancer in the current era of advances in chemotherapy and immunotherapy.
The innovation of novel systemic chemo/immunotherapy for metastatic head and neck cancer might contribute to prognostic improvement. We aimed to clarify the recent characteristics and outcomes of pulmonary metastasectomy for head and neck cancer. Twenty-five patients who underwent pulmonary metastasectomy from January 2011 to December 2016 were included. The clinicopathological factors and survival were assessed by retrospective chart reviews. The median follow-up period was 39 months (range, 7-94 months). The median age was 66 years (range, 20-89 years), and 23 males were included. The primary tumor locations were as follows: pharynx (n = 12), nasal/paranasal cavity (n = 5), larynx (n = 4), and others (n = 4). The 5-year overall survival rate was 49%. In the univariate analysis, a history of local recurrence before pulmonary metastasis was an independent predictor of a poor prognosis. In 90% of patients with recurrence after pulmonary metastasectomy, the site of recurrence was the lung. Eight patients achieved long-term survival without any evidence of recurrence (median: 45 months). Molecular targeting chemotherapy and immune-checkpoint inhibitors were used in five patients with systemic recurrence after pulmonary metastasectomy, leading to preferable survival. In the current era of advances in systemic chemotherapy and immunotherapy, surgical indication has not changed for resectable pulmonary metastases and selected patients can still benefit from pulmonary metastasectomy. Further investigation is needed to clarify the significance of systemic therapy in patients with pulmonary metastasis of head and neck cancer.


Long-term citalopram maintenance in mice: selective reduction of alcohol-heightened aggression.
Selective serotonin reuptake inhibitors (SSRIs) alleviate many affective disturbances in human clinical populations and are used in animal models to study the influence of serotonin (5-HT) on aggressive behavior and impulsivity. We hypothesized that long-term SSRI treatment may reduce aggressive behavior escalated by alcohol consumption in mice. Therefore, aggression was tested in male CFW mice to determine whether repeated citalopram (CIT) administration reduces alcohol-heightened aggression. Resident male mice self-administered alcohol by performing an operant response on a panel placed in their home cage that delivered a 6% alcohol solution. Mice repeatedly confronted an intruder 15 min after self-administration of either 1 g/kg alcohol (EtOH) or water (H(2)O). Aggressive behaviors were higher in most mice when tests occurred after EtOH intake relative to H(2)O. Once baseline aggression was established, animals were injected (i.p.) twice daily with 10 mg/kg CIT or saline (SAL) for 32 days. Every 4 days throughout the CIT treatment period, aggressive encounters occurred 6 h after CIT injections, with testing conditions alternating between EtOH and H(2)O intake. Aggression was only modestly affected by CIT in the first 2 weeks of treatment. However, by day 17 of CIT treatment, alcohol-heightened aggressive behavior was abolished, while baseline aggression remained stable. These data lend support for the role of the 5-HT transporter in the control of alcohol-related aggressive behavior, and the time course of effects suggests that a change in density of 5HT(1A) autoreceptors is necessary before antidepressant drugs produce beneficial outcomes.


The use of aminophylline for correction of haemodynamic repercussions of clamping of the aorta.
Occlusion of the abdominal aorta induces an increased impedance to ejection, leading to a reduction in cardiac output. The magnitude of the haemodynamic disturbances seemed important enough to justify the use of a vasodilator drug. In that respect the use of aminophylline was evaluated in twelve patients. The potentially dangerous increase in systemic resistance is prevented by aminophylline, which effectively neutralizes the increase in afterload. Moreover, a positive inotropic action can be inferred from the increase in stroke volume and ventricular systolic work. It must be stressed that this drug must be withheld in patients with cardiac irritability, for it has a beta-mimetic action.


[Therapeutic Factors in Offender Treatment: A Systematic Review].
This paper presents a systematic literature review of international research on therapeutic factors in offender treatment. The review was based on the PRISMA criteria; PsycINFO and PSYNDEX as well as references given in included studies were browsed. Only quantitative empirical studies published between 1990 and 2018 were included. In this paper, evidence for common factors (therapeutic alliance, social climate, feedback) and therapist factors (interpersonal skills/characteristics, personality, therapy expectations) from 19 journal articles are reported. Some tendencies emerged, but there was no conclusive evidence on the effect of common factors and therapist factors on the therapy outcome. This non-conclusive evidence is mostly due to the methodological shortcomings of primary studies, heterogeneity of outcome variables and the low number of studies that looked at each of these variables. In sum, there is not enough evidence to date to show a strong relationship between common factors and therapist factors and a (positive) outcome in the treatment of offenders.


Secondary peripheral chondrosarcoma arising in solitary osteochondroma: variables influencing prognosis and survival.
Secondary peripheral chondrosarcomas arising in solitary osteochondromas is an unusual complication, reported in small series. In this study, we aimed to present our experience with this rare variant of chondrosarcoma and compare results with already published data in order to determine prognostic factors for overall and disease-free survival. The case study includes retrospective data from patients diagnosed at a single institution from 1943 to 2019. Clinical data were collected reviewing all available medical records from first to last follow-up visits. To exclude the presence of the Multiple Osteochondroma Hereditary Syndrome, few patients, with a suspect of a familial form of the disease, were evaluated for the presence of germline heterozygous variants in EXT1 and EXT2 genes. Results were summarized using descriptive statistics and statistical analysis were performed to reveal associations between variables. Two hundred and fourteen secondary peripheral chondrosarcomas that arose exclusively from solitary osteochondromas diagnosed in a multidisciplinary setting at the IRCCS Istituto Ortopedico Rizzoli were retrospectively identified, 66.4% males and 33.6% females with a median age at diagnosis of 38 years. The local recurrence rate was 17.3%, while the metastases one was 5.1%. Besides age, a high histologic grade is the only factor associated with worse 5-year and 10-year overall survival (log-rank p = 0.0005, HR = 3.74; 95% CI 1.69-8.26). Moreover, high histological grade (HR = 3.75; 95% CI = 1.69-8.34; p = 0.001) and surgical debulking (HR = 3.71; 95% CI = 1.57-8.79; p = 0.003) were associated with a significantly worse disease-free survival. Our study confirm the low-grade behavior of secondary peripheral chondrosarcomas and demonstrate that the best choice of treatment for those arising in solitary osteochondromas is the wide surgical excision, when possible. Location per se is not a factor that affects prognosis, while the accurate histological grade assessment is correlated with the tumor aggressiveness and a long term follow up is necessary for this rare variant of chondrosarcoma.


Outcomes from anomalous origin of the left coronary artery from the pulmonary artery repair: Long-term complications in relation to residual myocardial abnormalities.
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary artery irregularity. This study aimed to clarify the long-term postoperative outcomes in ALCAPA patients, and to compare the infantile and adult types. We retrospectively analyzed the clinical data from 33 patients with ALCAPA who underwent surgical repairs after 1980. The patients were grouped based on whether presentation occurred before (infantile type: n=14) or after (adult type: n=19) 1 year of age. The mean follow-up duration was 16 years. Preoperatively, the infantile type had greater impairment of the left ventricle ejection fraction (LVEF) (45±15%) compared with the adult type (59±10%) (p<0.01). Coronary revascularization significantly improved the postoperative LVEF (67±5%) (p<0.01) in the patients with the infantile type. The postoperative LVEF did not change in the adult type. The mitral regurgitation (MR) severity improved postoperatively, but the between-group difference was not significant. Postoperatively, none of the patients with the infantile type and 37% of the patients with the adult type had left ventricular asynergy (p=0.01), and both groups showed postoperative perfusion defects (79% vs 95%, p=0.29). Compared with the infantile type, the adult type had a significant prognostic value for composite cardiovascular events that comprised cardiac death, arrhythmias, MR deterioration, and hospitalization as a consequence of heart failure (p=0.04). Most patients showed favorable clinical outcomes postoperatively, but myocardial damage remained long after surgery and cardiovascular events occurred postoperatively. Hence, meticulous long-term follow-up is warranted.


The paradoxical response of growth hormone (GH) to thyrotropin-releasing hormone (TRH) in constitutionally tall children involves a cholinergic pathway.
To investigate whether or not a cholinergic pathway is involved in the paradoxical response of GH to TRH in constitutionally tall children, we studied 8 healthy prepubertal children aged 4 2/12-7 10/12 yr, whose heights were over the 95th percentile of the NCHS tables. We defined as "paradoxical" a GH increment greater than 5 ng/ml in response to TRH. Five out of 8 children showed a paradoxical response of GH to TRH (mean GH peak after TRH of 10.7 +/- 1.1 ng/ml). Pretreatment with atropine (0.01 mg/kg IM 30 min prior to the TRH administration) abolished the TRH induced GH rise (peak GH after TRH of 1.5 +/- 1.0 ng/ml, p less than 0.01) but did not modify the TSH response (peak TSH after TRH: basal conditions 8.7 +/- 0.8 microU/ml, post atropine: 9.5 +/- 1.4 microU/ml, p greater than 0.05). Our results demonstrate that a cholinergic pathway is involved in the paradoxical response of GH to TRH in constitutionally tall children.


Evaluation matters: lessons learned on the evaluation of surgical teaching.
The traditional system of academic promotion and tenure can make it difficult to reward those who excel at surgical teaching. A successful faculty evaluation process can provide the objective measures of teaching performance needed for performance appraisals and promotion decisions. Over the course of two decades, an extensive faculty evaluation process has been developed in the Department of Surgery at the University of Toronto. This paper presents some of the non-psychometric characteristics of that system. Faculty awareness of the evaluation process, the consistency of its application, trainee anonymity and the materiality of the results are described key factors of a faculty evaluation system that meets the assessment needs of individual teachers and raises the profile of teaching in surgical departments.


Ultrastructural changes of secretory cells of salamander lingual salivary glands under varying conditions.
In general the ultrastructure of secretory cells can be modified under secretory stimulated and non-stimulated conditions. The ultrastructure of the lingual salivary glands of hibernating salamanders in the natural environment was examined and compared to those of fasted and fed animals kept in the laboratory. Hibernating salamanders of the species Hynobius tokyoensis were collected from the natural environment during the winter breeding season and sacrificed for this study. One group was sacrificed immediately, another group was kept under fasted condition, and another group was regularly fed; both of the latter groups were kept at room temperature for 1 month and then sacrificed. The tongue was fixed for electron microscopy and processed by conventional method, and semithin sections were histochemically examined for glycoconjugates. The lingual salivary glands of this salamander species were composed of simple or often branched tubular glands opening onto the dorsal surface of the tongue. The secretory cells which composed their terminal portions were all columnar in morphology and histochemically mucous in nature. Under hibernation or prolonged fasting at room temperature, the mucous granules of these columnar secretory cells were decreased in number and the Golgi apparatus appeared inactive. A conspicuous structural peculiarity was multiple fingerprint-like structures of the rough-surfaced endoplasmic reticulum (RER). Most of these membranes were composed of stacks of tightly packed cisternae. Under regular feeding, the mucous granules were closely packed in the cytoplasm of the secretory cells and the basal nucleus was slightly enlarged. The Golgi apparatus showed progressive activation with distended saccules. The unique membranous arrangement of the RER which was observed in the fasting animals was completely absent, and the cisternae were irregular in width with considerable variation of the intercisternal spaces. The tongue of the salamander H. tokyoensis has numerous tubular salivary glands which are mucous in nature. The architecture of the organelles in the secretory cells is subject to modification in response to the cellular metabolism.


Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation.
The common delta F508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) interferes with the biosynthetic folding of nascent CFTR polypeptides, leading to their retention and rapid degradation in an intracellular compartment proximal to the Golgi apparatus. Neither the pathway by which wild-type CFTR folds nor the mechanism by which the Phe508 deletion interferes with this process is well understood. We have investigated the effect of glycerol, a polyhydric alcohol known to stabilize protein conformation, on the folding of CFTR and delta F508 in vivo. Incubation of transient and stable delta F508 transfectants with 10% glycerol induced a significant accumulation of delta F508 protein bearing complex N-linked oligosaccharides, indicative of their transit to a compartment distal to the endoplasmic reticulum (ER). This accumulation was accompanied by an increase in mean whole cell cAMP activated chloride conductance, suggesting that the glycerol-rescued delta F508 polypeptides form functional plasma membrane CFTR channels. These effects were dose- and time-dependent and fully reversible. Glycerol treatment also stabilized immature (core-glycosylated) delta F508 and CFTR molecules that are normally degraded rapidly. These effects of glycerol were not due to a general disruption of ER quality control processes but appeared to correlate with the degree of temperature sensitivity of specific CFTR mutations. These data suggest a model in which glycerol serves to stabilize an otherwise unstable intermediate in CFTR biosynthesis, maintaining it in a conformation that is competent for folding and subsequent release from the ER quality control apparatus.


Is ubiquinone diffusion rate-limiting for electron transfer?
The different possible dispositions of the electron transfer components in electron transfer chains are discussed: random distribution of complexes and ubiquinone with diffusion-controlled collisions of ubiquinone with the complexes, random distribution as above, but with ubiquinone diffusion not rate-limiting, diffusion and collision of protein complexes carrying bound ubiquinone, and solid-state assembly. Discrimination among these possibilities requires knowledge of the mobility of the electron transfer chain components. The collisional frequency of ubiquinone-10 with the fluorescent probe 12-(9-anthroyl)stearate, investigated by fluorescence quenching, is 2.3 X 10(9) M-1 sec-1 corresponding to a diffusion coefficient in the range of 10(-6) cm2/sec (Fato, R., Battino, M., Degli Esposti, M., Parenti Castelli, G., and Lenaz, G., Biochemistry, 25, 3378-3390, 1986); the long-range diffusion of a short-chain polar Q derivative measured by fluorescence photobleaching recovery (FRAP) (Gupte, S., Wu, E. S., Höchli, L., Höchli, M., Jacobson, K., Sowers, A. E., and Hackenbrock, C. R., Proc. Natl. Acad. Sci. USA 81, 2606-2610, 1984) is 3 X 10(-9) cm2/sec. The discrepancy between these results is carefully scrutinized, and is mainly ascribed to the differences in diffusion ranges measured by the two techniques; it is proposed that short-range diffusion, measured by fluorescence quenching, is more meaningful for electron transfer than long-range diffusion measured by FRAP, or microcollisions, which are not sensed by either method. Calculation of the distances traveled by random walk of ubiquinone in the membrane allows a large excess of collisions per turnover of the respiratory chain. Moreover, the second-order rate constants of NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase are at least three orders of magnitude lower than the second-order collisional constant calculated from the diffusion of ubiquinone. The activation energies of either the above activities or integrated electron transfer (NADH-cytochrome c reductase) are well above that for diffusion (found to be ca. 1 kcal/mol). Cholesterol incorporation in liposomes, increasing bilayer viscosity, lowers the diffusion coefficients of ubiquinone but not ubiquinol-cytochrome c reductase or succinate-cytochrome c reductase activities. The decrease of activity by ubiquinone dilution in the membrane is explained by its concentration falling below the Km of the partner enzymes. It is calculated that ubiquinone diffusion is not rate-limiting, favoring a random model of the respiratory chain organization.(ABSTRACT TRUNCATED AT 400 WORDS)


A biometrical-genetic analysis of granule cell number in the area dentata of house mice.
Considerable variability in the number of granule cells in the area dentata has been found among inbred strains of mice. In this report a simplified triple-test cross breeding design was employed to identify and discriminate between heritable and non-heritable sources of this variability. Granule cell numbers were estimated in two previously identified extreme strains of mice and in their reciprocal F1 hybrids with 3 strains of mice known to be intermediate between the 2 extremes. Analytical techniques of biometrical genetics applied to the neuron number estimates indicated that genetic transmission of this trait involves genes located upon autosomes. Transmission does not involve cytoplasmic factors within the female egg, or maternally-mediated differences in nutrition. Of the total variability in dentate granule cell number, 86% is estimated to be determined by an additive genetic component. A dorsal-to-ventral increase in the size of granule cell nuclei was found for all genotypes; some possible bases for this increase are discussed.


Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine.
Immunogenic cell death is characterized by damage-associated molecular patterns, which can enhance the maturation and antigen uptake of dendritic cells. Shikonin, an anti-inflammatory and antitumor phytochemical, was exploited here as an adjuvant for dendritic cell-based cancer vaccines via induction of immunogenic cell death. Shikonin can effectively activate both receptor- and mitochondria-mediated apoptosis and increase the expression of all five tested damage-associated molecular patterns in the resultant tumor cell lysates. The combination treatment with damage-associated molecular patterns and LPS activates dendritic cells to a high maturation status and enhances the priming of Th1/Th17 effector cells. Shikonin-tumor cell lysate-loaded mature dendritic cells exhibit a high level of CD86 and MHC class II and activate Th1 cells. The shikonin-tumor cell lysate-loaded dendritic cell vaccines result in a strong induction of cytotoxic activity of splenocytes against target tumor cells, a retardation in tumor growth, and an increase in the survival of test mice. The much enhanced immunogenicity and efficacy of the current cancer vaccine formulation, that is, the use of shikonin-treated tumor cells as cell lysates for the pulse of dendritic cells in culture, may suggest a new ex vivo approach for developing individualized, dendritic cells-based anticancer vaccines.


A genetic variant in the gene encoding the stress70 protein chaperone family member STCH is associated with gastric cancer in the Japanese population.
Association analysis, based on linkage disequilibrium between specific alleles in the candidate loci and nearby genetic markers, has been proposed to identify genes conferring susceptibility to multifactorial diseases. Using the affected sib-pair method, we previously mapped four candidate chromosomal regions, 1p32, 2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To identify genes involved in the disease, we performed a gene-based association analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We found a significant association of five SNPs in the stress70 protein chaperon family member STCH gene with gastric cancer, especially with the non-cardia localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of haplotype frequency showed significant association between TTGGC haplotype and gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the Japanese population, STCH might be a new candidate for conferring susceptibility to this disease.


Reported parental age of death in type 2 diabetic patients with and without established diabetic nephropathy.
Diabetic patients with renal disease have increased mortality, largely from cardiovascular disease. This could be related to insulin resistance or to other inherited factors. The aim of the present study was to investigate whether there is evidence of the familial aggregation of increased mortality, even in the absence of diabetes, by studying the reported parental age of death in type 2 diabetes. Patients with type 2 diabetes and nephropathy (group A), patients with type 2 diabetes but without nephropathy (group B) and normal controls (group C) were interviewed and asked to report the age of death of their parents. The mean (+/-standard deviation) parental age of death was 68.2 (+/-13.8) years in group A, 67.3 (+/-16.0) years in group B and 68.1 (+/-14.9) years in group C. There was no statistical difference between any of the groups. Our preliminary study has failed to show evidence of reduced life expectancy of parents of patients with type 2 diabetes and nephropathy.


Identification of a low moleculr weight IgM antibody with treponema pallidum specificity in sera of patients with chronic syphilis.
A low-molecular (8S) treponema-specific IgM antibody was isolated by means of Sephadex 200 G gel filtration and/or sucrose gradient ultracentrifugation in 78 of 4,120 sera of patients who had been identified to have had syphilis. The IgM specificity can be shown by indirect immunofluorescence using a mu-chain specific antiserum. The low molecular IgM (LMW-IgM) antibodies are not identical with the 19S-IgM as demonstrated in studies with gel filtration and sucrose gradient methods. They are not identical neither with 7S IgG or IgA. Neither the presence of antinuclear nor rheumatic factor could be shown in the LMW-IgM fraction. In most of the patients with LMW-IgM antibody, there existed a treponema infection of late latency.


Self-assembled graphene-based microfibers with eclectic optical properties.
The construction of graphene-based microfibers with reinforced mechanical and electrical properties has been the subject of numerous researches in recent years. However, the fabrication of graphene-based fibers with remarkable optical features still remains a challenge and has not been addressed so far. This paper aims to report a series of flexible self-assembled fibers, synthesized through a few-minute sonication of thermally oxidized graphene oxide nanosheets, so-called Nanoporous Over-Oxidized Graphene (NOG), in an acidic medium. These free-standing glassy fibers were classified into four distinct morphological structures and displayed a collection of intriguing optical properties comprising high transparency, strong birefringence, fixed body colorations (e.g. colorless, blue, green, and red), tunable interference marginal colorations, UV-visible-near IR fluorescence, and upconversion emissions. Moreover, they exhibited high chemical stability in strongly acidic, basic, and oxidizing media. The foregoing notable attributes introduce the NOG fiber as a promising candidate both for the construction of graphene-based photoluminescent textiles and the development of a wide variety of optical applications.


The Mediating Role of Self-Efficacy in the Association Between Diabetes Education and Support and Self-Care Management.
A total of 1,318 participants were included in the study (mean age = 52.9 years, SD = 9.6; 72.5% female, 56.4% Black, 3.1% Hispanic). Diabetes education was associated with increases in self-care activity scores related to general diet, physical activity, glucose self-monitoring, and foot care; care coordination was associated with glucose self-monitoring. In addition, mediation analysis models confirmed that improvements in self-efficacy led to improved self-care activities scores, mediating the association of diabetes education and self-care activities. Diabetes education and self-efficacy were associated with better self-care. Receiving diabetes education led to a higher likelihood of engaging in self-care activities, driven in part by increases in self-efficacy. Future interventions that aim to improve diabetes self-management behaviors can benefit from targeting self-efficacy constructs and from the integration of diabetes education in the care coordination structure.


Peritoneal macrophages from adjuvant arthritic rats enhance tumour cell growth in vitro.
Peritoneal macrophages from rats with adjuvant arthritis enhance the incorporation of 3H-thymidine in 2 tumour cell lines in vitro. Maximal enhancement is found during the development of the secondary lesions, and it is suggested that the immunologic commitment of the macrophages could interfere with their regulation of tumour cell proliferation in vivo.


The genus Rosalba Thomson, 1864 (Coleoptera, Cerambycidae, Lamiinae, Apomecynini).
Nineteen new species are described: Rosalba wappesi, from Bolivia; R. giesberti, from Bolivia; R. skillmani, from Bolivia; R. lingafelteri, from Bolivia; R. senecauxi, from French Guiana; R. dalensi, from French Guiana; R. giuglarisi, from French Guiana; R. nearnsi, from French Guiana; R. cerdai, from French Guiana; R. gaianii, from Venezuela; R. pittieri, from Venezuela; R. clinei, from Bolivia and Brazil; R. morrisi, from Costa Rica and Panama; R. schneppi, from Panama; R. birai, from Colombia; R. stenodesma, from Venezuela and French Guiana; R. similis, from Peru and Ecuador; R. bezarki, from Ecuador; and R.seraisorum, from Ecuador and Brazil (Amazonas). The following new synonymies are established: Aletretia dissimilis Belon, 1903 = A. fimbriata Belon, 1903; Aletretia consobrina Melzer, 1934, Rosalba gounellei Galileo Martins, 2013 and Rosalba vanini Galileo Martins, 2013 = Aletretia inscripta Bates, 1866; Aletretia mediofasciata Breuning, 1943 = Aletretia bucki Melzer, 1934; Aletretia peraffinis Breuning, 1940 = Aletretia approximata Melzer, 1934. The following species are redescribed: Rosalba strandiella (Breuning, 1940); and Rosalba rufescens (Breuning, 1940). The following new records are reported: Rosalba strandiella for Bolivia; R. strandi (Breuning, 1943) from the Brazilian states of São Paulo, Paraná and Santa Catarina; R. inscripta from Peru and the Brazilian state of Acre; R. smaragdina (Breuning, 1940) from the Brazilian state of Minas Gerais; R. obliqua (Thomson, 1868) from Brazil; and Rosalba fimbriata (Belon, 1903) from Ecuador.


Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner.
Transcription factor FoxO1 promotes hepatic glucose production. Genetic inhibition of FoxO1 function prevents diabetes in experimental animal models, providing impetus to identify pharmacological approaches to modulate this function. Altered Notch signaling is evident in tumorigenesis, and Notch antagonists are in clinical testing for application in cancer. Here we report that FoxO1 and Notch coordinately regulate hepatic glucose metabolism. Combined haploinsufficiency of FoxO1 and Notch1 markedly raises insulin sensitivity in diet-induced insulin resistance, as does liver-specific knockout of the Notch transcriptional effector Rbp-Jκ. Conversely, Notch1 gain-of-function promotes insulin resistance in a FoxO1-dependent manner and induces glucose-6-phosphatase expression. Pharmacological blockade of Notch signaling with γ-secretase inhibitors raises insulin sensitivity after in vivo administration in lean mice and in obese, insulin-resistant mice. The data identify a heretofore unknown metabolic function of Notch and suggest that Notch inhibition is beneficial in diabetes treatment, in part by helping to offset excessive FoxO1-driven hepatic glucose production.


Parenchymal Volume Replacement by Renal Cell Carcinoma Prior to Intervention: Predictive Factors and Functional Implications.
To analyze predictors, extent and functional implications associated with renal parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) prior to intervention. This phenomenon is well-recognized yet not adequately studied, and, if severe, can influence management. A retrospective review was performed of partial nephrectomy (PN) and radical nephrectomy (RN) patients with available preoperative nuclear-renal-scan and imaging demonstrating solitary RCC with normal contralateral kidney. Normal renal parenchymal volume of each kidney was measured by free-hand scripting from preoperative axial images. Primary endpoint was percent PVR which was estimated assuming that the contralateral-kidney serves as a control: PVR = (volume contralateral kidney - volume ipsilateral kidney) normalized by volume contralateral kidney. Multivariable linear-regression analysis assessed factors associated with preoperative PVR. Further analysis evaluated the functional effect of PVR prior to surgery. 146 PN and 136 RN patients with necessary studies were analyzed. For RN, the median PVR was 15% and a quarter of patients had PVR ≥27%. In contrast, PVR was negligible in PN patients for whom median preoperative parenchymal volumes were nearly identical in the ipsilateral/contralateral kidneys (179/180cc, respectively). PVR inversely correlated with preoperative renal function in the ipsilateral kidney (P <.01). Tumor-size (P <.01), stage (P = .03), and endophytic properties (P = .03) associated with PVR on multivariable-analysis. Our data suggest that substantial replacement of normal parenchyma by RCC occurs in many patients selected for RN and can contribute to preexisting renal-insufficiency. PVR prior to intervention is mainly driven by tumor characteristics in RN patients, but is negligible in most PN patients.


Skewed Invariant Natural Killer T (iNKT) Cells, Impaired iNKT:B Cell Help and Decreased SAP Expression in Blood Lymphocytes from Patients with Common Variable Immunodeficiency.
Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4-/CD8- and CCR5+/CXCR3+. These findings were associated with an enrichment of memory-like and a tendency towards a reduction in TNF-α-expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer-pulsed iNKT cells are not able to induce autologous B cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co-cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Finally, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B cell help in CVID.


Biosynthesis of silver nanoparticles by using of the marine brown alga Padina pavonia and their characterization.
Silver nanoparticles (AgNPs) are gaining considerable importance due to their attractive physicochemical properties for many applications. In the present study, (Ag NPs) were synthesized by the reduction of aqueous solutions of silver nitrate (AgNO3) with powder and solvent extracts of Padina pavonia (brown algae). The obtained nanoparticles exhibited high stability, rapid formation of the biogenic process (2 min -3 h), small size (49.58-86.37 nm) (the diameter of formed nanoparticles was measured by TEM and DLS) and variable shapes (spherical, triangular, rectangle, polyhedral and hexagonal). Preliminary characterization of nanoparticles was monitored by using UV-visible spectroscopy (UV-vis), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS) and finally by Fourier Transform Infrared spectroscopy (FTIR). The ratios of converted Ag NPs were recorded as 88.5; 86.2 and 90.5% in case of P. pavonia powder. extract and chloroform extract, respectively.


Lack of persisting antibody in a post-transplant patient after vaccine-strain varicella.
LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post-transplant, children without severe immunosuppression can generate anti-varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear. A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine-type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again. This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine-type strain, repeated vaccinations may be necessary for post-transplant patients who develop varicella.


A conserved region in the sigma54-dependent activator DctD is involved in both binding to RNA polymerase and coupling ATP hydrolysis to activation.
Rhizobium melioti DctD activates transcription from the dctA promoter by catalysing the isomerization of closed complexes between sigma54-RNA polymerase holoenzyme and the promoter to open complexes. DctD must make productive contact with sigma54-holoenzyme and hydrolyse ATP to catalyse this isomerization. To define further the activation process, we sought to isolate mutants of DctD that had reduced affinities for sigma54-holoenzyme. Mutagenesis was confined to the well-conserved C3 region of the protein, which is required for coupling ATP hydrolysis to open complex formation in sigma54-dependent activators. Mutant forms of DctD that failed to activate transcription and had substitutions in the C-terminal half of the C3 region were efficiently cross-linked to sigma54 and the beta-subunit of RNA polymerase, suggesting that they bound normally to sigma54-holoenzyme. In contrast, some mutant forms of DctD with amino acid substitutions in the N-terminal half of the C3 region had reduced affinities for sigma54 and the beta-subunit in the cross-linking assay. These data suggest that the N-terminal half of the C3 region of DctD contains a site that may contact sigma54-holoenzyme during open complex formation.


Human spike potentials prior to saccades and optokinetic nystagmus fast phases: effects of instructions, eye movement direction and electrode laterality.
Presaccadic potentials in humans consist of 3 components, a slow negative shift, a positive antecedent potential and a spike potential (SP). This study demonstrated the presence of the SP before another class of rapid eye movements, fast phases of optokinetic nystagmus (OKN), in 11 right-handed, normal human subjects and compared the amplitude of the averaged SP for OKN fast phases, recorded at P3 and P4 (International 10/20 System), with the SP amplitude for 10 degrees self-paced saccades between two red light-emitting diodes. In particular, the effects of electrode laterality, rapid eye movement direction and two sets of instructions during the OKN task were assessed. Subjects were told to either 'look at the screen' (OKN1 paradigm) or to 'try to slow or stop the motion of the pattern' (OKN2 paradigm) during presentation of optokinetic stimulation. As in the case of saccades, the OKN fast phase velocity spike was used to trigger the signal averager (Nicolet (CA-1000]. There were two significant differences in SP amplitude prior to saccades and OKN fast phases. First, 3-way analysis of variance (ANOVA) and Newman-Keuls comparisons revealed that the SP was attenuated significantly for OKN for either eye movement direction over either left or right recording sites (F = 16.045, P less than 0.001). This effect was not related to amplitude differences in eye movements in the different tasks, although a contribution of variance in the OKN fast phase amplitudes cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)


Differences in synaptic size in the superficial and deep layers of the molecular layer of the cerebellar cortex of the cat. An electronmicroscopic and autoradiographic study.
In a previous study observations in semithin sections of E-PTA-stained cerebellar cortex of the cat revealed differences in size of synaptic grids between the molecular and granular layer (Van der Want et al. 1984). In addition, synaptic size differences were observed between superficial and deep levels in the molecular layer. The present study was an attempt to analyze synapses in ultrathin sections of the cerebellar cortex with special emphasis on size differences of distinct types of synapses at different levels in the molecular layer. Climbing fibers were identified by means of anterograde transport of 3H-leucine injected in the inferior olive and parallel fibers were identified on account of fine structural criteria. Synaptic profiles were measured semi-automatically in the neuropil of the cerebellar cortex at the supra-Purkinje level and the subpial level. Measurements of the trace- and chordlength were obtained from random sections. The frequency distribution of the true diameters of the synapses was reconstructed with a discrete "unfolding"-procedure. The overall diameter at the superficial level was 390.2 +/- 1.5 nm, at the deep level 406.6 +/- 1.5 nm. Climbing fibers exhibited mean values of 431.9 +/- 4.7 and 461.3 +/- 4.1 nm at these levels and parallel fiber terminals mean values of 370.7 +/- 2.9 and 395.8 +/- 3.0 nm. The frequency distributions showed remarkable and statistically significant differences compared with the overall distributions observed at the superficial and the deep levels respectively. The frequency distributions of synaptic diameters at the superficial and deep levels also differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis.
VCells are constantly exposed to various types of stress, and disruption of the proper response leads to a variety of diseases. Among them, inflammation and apoptosis are important examples of critical responses and should be tightly regulated, as inappropriate control of these responses is detrimental to the organism. In several disease states, these responses are abnormally regulated, with adverse effects. Apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases that regulate inflammation and apoptosis after a variety of stimuli, such as oxidative stress and endoplasmic reticulum stress. In this review, we summarize recent reports on the ASK family in terms of their involvement in inflammatory diseases, focussing on upstream stimuli that regulate ASK family members.


Polaronic Contributions to Friction in a Manganite Thin Film.
Despite the huge importance of friction in regulating movement in all natural and technological processes, the mechanisms underlying dissipation at a sliding contact are still a matter of debate. Attempts to explain the dependence of measured frictional losses at nanoscale contacts on the electronic degrees of freedom of the surrounding materials have so far been controversial. Here, it is proposed that friction can be explained by considering the damping of stick-slip pulses in a sliding contact. Based on friction force microscopy studies of La(1- x )Sr x MnO3 films at the ferromagnetic-metallic to a paramagnetic-polaronic conductor phase transition, it is confirmed that the sliding contact generates thermally-activated slip pulses in the nanoscale contact, and argued that these are damped by direct coupling into the phonon bath. Electron-phonon coupling leads to the formation of Jahn-Teller polarons and to a clear increase in friction in the high-temperature phase. There is neither evidence for direct electronic drag on the atomic force microscope tip nor any indication of contributions from electrostatic forces. This intuitive scenario, that friction is governed by the damping of surface vibrational excitations, provides a basis for reconciling controversies in literature studies as well as suggesting possible tactics for controlling friction.


Asynchronous Online Instruction Leads to Learning Gaps When Compared to a Flipped Classroom.
With the gradual shift to online education models that has taken place in recent decades, research has sought to understand the nuances of student performance in an online model in comparison to more traditional in-person modalities. However, the effects of instructional modality have been difficult to determine given the many variables that exist in course design between these methods. In this study, we attempt to determine the efficacy of asynchronous online instruction by comparing two nearly equivalent courses. The first course was a flipped classroom, a recent and well-studied hybrid model of instruction. The second was an asynchronous fully online course that contained all the same instructional elements as the in-person course but lacked any student or instructor interaction. Student performance was tracked at both a highly-selective private institution and an open-enrollment public institution. Results show that students' performance drops in an asynchronous online course compared to an equivalent in-person experience. Several potential hypotheses are put forth to explain a change in performance that can potentially shape the design of online instruction.


Unbalanced reciprocal translocations in cases of Prader-Willi syndrome.
A case of Prader-Willi syndrome (PWS) associated with a de novo unbalanced 15q;17q reciprocal translocation presumptively resulting from the tertiary monosomic form of 3:1 meiotic disjunction is described. Twenty-three similar unbalanced translocations have been identified from the literature. The 24 karyotypes are characterised by having 45 chromosomes, monosomy for the pericentromeric region of chromosome 15 (range pter----q11 to q21), and little monosomy of the recipient (non-15) chromosome. Two-thirds of the cases with these karyotypes have phenotypic features of PWS. It seems probable that (i) where unbalanced reciprocal translocations are associated with PWS, they will almost invariably be presumptive segregants of the tertiary monosomic form of 3:1 disjunction and (ii) the majority of cases found with this type of karyotype, particularly it appears when de novo in origin, will be associated with phenotypic features of PWS.


Correlation between crossed cerebellar diaschisis and clinical neurological scales.
A common consequence of unilateral stroke is crossed cerebellar diaschisis (CCD), a decrease in regional blood flow (CBF) and metabolism (CMRglu) in the cerebellar hemisphere contralateral to the affected cerebral hemisphere. Former studies indicated a post-stroke time-dependent relationship between the degree of CCD and the clinical status of acute and sub-acute stroke patients, but no study has been performed in post-stroke patients. The objective of this investigation was to evaluate the quantitative correlation between the degree of CCD and the values of clinical stroke scales in post-stroke patients. We measured with positron emission tomography (PET) regional CBF and CMRglu values in the affected cortical regions and the contralateral cerebellum in ten ischaemic post-stroke patients. Based on these quantitative parameters, the degree of diaschisis (DoD) was calculated, and the DoD values were correlated with three clinical stroke scales [Barthel Index, Orgogozo Scale and Scandinavian Neurological Scale (SNS)]. There were significant linear correlations between all clinical stroke scales and the CCD values (Barthel Index and Orgogozo Scale: P < 0.001, for both CBF and CMRglu; SNS: P = 0.007 and P = 0.044; CBF and CMRglu, respectively). The findings indicate that DoD can be used as a quantitative indicator of the functional impairments following stroke, i.e. it can serve as a potential surrogate of the severity of the damage.


Ultrasound and microbubble mediated drug delivery: acoustic pressure as determinant for uptake via membrane pores or endocytosis.
Although promising results are achieved in ultrasound mediated drug delivery, its underlying biophysical mechanisms remain to be elucidated. Pore formation as well as endocytosis has been reported during ultrasound application. Due to the plethora of ultrasound settings used in literature, it is extremely difficult to draw conclusions on which mechanism is actually involved. To our knowledge, we are the first to show that acoustic pressure influences which route of drug uptake is addressed, by inducing different microbubble-cell interactions. To investigate this, FITC-dextrans were used as model drugs and their uptake was analyzed by flow cytometry. In fluorescence intensity plots, two subpopulations arose in cells with FITC-dextran uptake after ultrasound application, corresponding to cells having either low or high uptake. Following separation of the subpopulations by FACS sorting, confocal images indicated that the low uptake population showed endocytic uptake. The high uptake population represented uptake via pores. Moreover, the distribution of the subpopulations shifted to the high uptake population with increasing acoustic pressure. Real-time confocal recordings during ultrasound revealed that membrane deformation by microbubbles may be the trigger for endocytosis via mechanostimulation of the cytoskeleton. Pore formation was shown to be caused by microbubbles propelled towards the cell. These results provide a better insight in the role of acoustic pressure in microbubble-cell interactions and the possible consequences for drug uptake. In addition, it pinpoints the need for a more rational, microbubble behavior based choice of acoustic parameters in ultrasound mediated drug delivery experiments.


Crystallization and preliminary X-ray analysis of an intact soluble-form variant surface glycoprotein from the African trypanosome, Trypanosoma brucei.
The intact variant surface glycoprotein (VSG) ILTat 1.24 from Trypanosoma brucei has been crystallized. An amino-terminal domain of the protein comprising two thirds of the sequence had been crystallized previously after proteolytic digestion. Now intact VSG crystals have been grown from 50 mM-Mes (pH 6.5) containing 62% (w/v) saturated ammonium sulfate. The crystals are demonstrated to contain the intact VSG by h.p.l.c. gel filtration and reaction with an antibody to the inositol phosphate oligosaccharide on the VSG carboxy terminus. The space group of the crystals is P6(2)22 (or P6(4)22) with unit cell dimensions a = b = 184 A and c = 214 A. Preparative isoelectric focusing may have facilitated crystallization.


Performance of dispersed oil and suspended sediment during the oil-sediment aggregation process.
Oil-sediment aggregation is an important transport and transformation process of spilled oil, which has been considered as a pathway of spill remediation. This work focused on the individual performance of dispersed oil and sediment during the aggregation process. Dispersion of three oils was first tested and validated in a water tank. An approach of estimating the mass variation of the sediment that has participated in forming the oil-sediment aggregates (OSAs) has been developed by density analysis. Results indicated that the density of the formed OSAs increases during the aggregation. In the context of remediation, it takes longer for sediment to reach equilibrium than for dispersed oil, especially under high mixing energy at a large sediment concentration, which results in the formation of dense OSAs, as well as high aggregation degree and rate. Roncador oil possesses a relatively high capability of capturing sediment to form dense OSAs, especially at an initial sediment concentration of over 150 mg/L. Oil sinking efficiency and the characteristic change rate of aggregated oil mass seem to be proportional to oil dispersion efficiency, and decrease with the mean size of dispersed oil droplets. The process of aggregation can further promote the dispersion of oil into water column. This study also provides fundamental data for the formation kinetics of OSAs.


Protocol for live-cell fluorescence-guided cryoFIB-milling and electron cryo-tomography of virus-infected cells.
Here, we present a protocol for assessing virus-infected cells using electron cryo-tomography (cryoET). It includes the basic workflows of seeding cells, plunge-freezing, clipping, cryo-focused ion beam milling (cryoFIB-milling), and cryoET, as well as two optional modules: micropatterning and live-cell fluorescence microscopy. We use an A549 human cell line and the virus HAdV5-pIX-mcherry in this protocol, but the comprehensive workflow can be easily transferred to other cell types and different types of virus infection or treatment. For complete details on the use and execution of this protocol, please refer to Pfitzner et al. (2021).


Prostate-Specific Membrane Antigen-Based PET Brings New Insights into the Management of Prostate Cancer.
Prostate cancer (PCa) is the third most common cancer diagnosed in the world. Since its first identification in 1987 and its first molecular cloning in 1993, prostate-specific membrane antigen (PSMA) has been developed as a theragnostic imaging biomarker and therapeutic agent for PCa. For metastatic castration-resistant PCa, PSMA-based PET imaging can be applied to the monitoring of disease and response assessment with PSMA-based therapeutics. This novel imaging modality is bringing new insights into diagnosis, stratification, and clinical decision-making and treatment.


Modulating the phenotype of host macrophages to enhance osteogenesis in MSC-laden hydrogels: Design of a glucomannan coating material.
The biomaterials-host interaction is a dynamic process in which macrophages play a vital role of regulation. Depending on the biochemical signals they sense, these highly plastic cells can mediate the immune response against the implanted scaffolds and/or exert regenerative potency to varying extent. Designing appropriate 'exterior signals' for scaffolds may exploit the power of endogenous macrophages to aid the regeneration of engineered tissues. To realise this goal, this study devised an injectable, instantaneously-solidifying coating material (acBSP) based on a unique, macrophage-affinitive glucomannan polysaccharide. Coating of three-dimensional hydrogel constructs with acBSP was rapid, neat and complete, requiring neither chemical reactions nor harsh conditions. Comprehensive in vitro analyses indicated that acBSP efficiently facilitated the adhesion and activation of macrophages and notably induced the macrophages to express pro-osteogenic/-angiogenic genes. Further in vivo assessment of acBSP-coated, mesenchymal stem cells-laden hydrogels in a murine dorsal subcutaneous pocket model demonstrated efficient macrophage activation, desirable scaffold-tissue integration and improved osteogenic differentiation in the delivered cells. In summary, by activating macrophages into a pro-osteogenic phenotype, the acBSP coating has demonstrated its competency as an innovative, open and efficacious platform to harness the power of host immunity for enhancing the regenerative performance of engineered tissue constructs.


Cost effectiveness of epidural steroid injections to manage chronic lower back pain.
The efficacy of epidural steroid injections in the management of chronic low back pain is disputed, yet the technique remains popular amongst physicians and patients alike. This study assesses the cost effectiveness of injections administered in a routine outpatient setting in England. Patients attending the Nottingham University Hospitals' Pain Clinic received two injections of methylprednisolone plus levobupivacaine at different dosages, separated by at least 12 weeks. Prior to each injection, and every week thereafter for 12 weeks, participants completed the EQ-5D health-related quality of life instrument. For each patient for each injection, total health state utility gain relative to baseline was calculated. The cost of the procedure was modelled from observed clinical practice. Cost effectiveness was calculated as procedure cost relative to utility gain. 39 patients provided records. Over a 13-week period commencing with injection, mean quality adjusted life year (QALY) gains per patient for the two dosages were 0.028 (SD 0.063) and 0.021 (SD 0.057). The difference in QALYs gained by dosage was insignificant (paired t-test, CIs -0.019 - 0.033). Based on modelled resource use and data from other studies, the mean cost of an injection was estimated at £219 (SD 83). The cost utility ratio of the two injections amounted to £8,975 per QALY gained (CIs 5,480 - 22,915). However, at costs equivalent to the tariff price typically paid to providers by health care purchasers, the ratio increased to £27,459 (CIs 16,779 - 70,091). When provided in an outpatient setting, epidural steroid injections are a short term, but nevertheless cost effective, means of managing chronic low back pain. However, designation of the procedure as a day case requires the National Health Service to reimburse providers at a price which pushes the procedure to the margin of cost effectiveness. ISRCTN 43299460.


[Diagnosis of postpartum abdominal pain: about a rare case of portal vein thrombosis].
We report the management of patient with acute abdominal pain in the immediate post-partum caesarean section performed in the context of preeclampsia. Acute portal vein thrombosis is diagnosed, in a patient with no personal or family history of venous thrombosis. Blood tests showed a protein C and S deficiencies. Portal vein thrombosis is an extremely rare occurrence in pregnancy and postpartum.


Molecular characterization of tick-borne bacteria and protozoans in yaks (Bos grunniens), Tibetan sheep (Ovis aries) and Bactrian camels (Camelus bactrianus) in the Qinghai-Tibetan Plateau Area, China.
Due to the specific plateau climate, a variety of unique animals live in the Qinghai-Tibetan Plateau Area (QTPA) including yaks (Bos grunniens), Tibetan sheep (Ovis aries) and Bactrian camels (Camelus bactrianus). However, information on tick-borne diseases (TBDs) in the QTPA and on the molecular characteristics of tick-borne pathogens (TBPs) in the area is limited. Therefore, the aim of this study was to investigate Anaplasma spp., Babesia spp., Theileria spp., Borrelia burgdorferi sensu lato and Rickettsia spp. infecting yaks, Tibetan sheep and camels in this area. A total of 276 animals were screened. Overall, 84.5% (164/194) of yaks, 58% (23/40) of Tibetan sheep, and 38% (16/42) of camels tested positive for at least one pathogen. Theileria spp., Anaplasma ovis and spotted fever group (SFG) Rickettsia spp. were detected as TBPs in the current study with overall infection rates of 10.9% (30/276), 8.3% (23/276) and 62.9% (171/276), respectively. Further study revealed that 1.5% (3/194) of the yaks were infected with Theileria sp. OT3, 1.5% (3/194) with T. luwenshuni, 6.2% (12/194) with T. uilenbergi, 1.1% (2/194) with T. ovis and 82% (159/194) with SFG Rickettsia spp. It was also shown that 58% (23/40) of the Tibetan sheep were infected with A. ovis and 15% (6/40) with T. ovis. Among the camels, 10% (4/42) were infected with T. equi, while 29% (12/42) were positive for Rickettsia spp. Sequence analysis revealed that the Rickettsia spp. infecting yaks and camels were Rickettsia raoultii and Rickettsia slovaca. To the best of our knowledge, this study reports the first detection and characterization of these pathogens in yaks, Tibetan sheep and camels in the country, except for T. luwenshuni infections in yaks.


Bidirectional effects between parenting sensitivity and child behavior: A cross-lagged analysis across middle childhood and adolescence.
Using a longitudinal, cross-lagged design, this study examined the bidirectional relations between mothers' and fathers' sensitivity and children's externalizing (EXT) and internalizing (INT) behavior from middle childhood into adolescence. The subsample comprised families (N = 578) in which the mother and father cohabitated from the study's first time point (child age = 54 months) through Age 15 in the longitudinal NICHD Study of Early Child Care and Youth Development. Study results revealed differential patterns for mother-child and father-child relations in the full sample and separately for males and females. The full cross-lagged models revealed that child EXT behavior predicted maternal sensitivity, but not vice versa, and fathers' sensitivity and child behavior were reciprocally interrelated. There was a significant indirect pathway from early paternal sensitivity to later EXT in males, and from early maternal sensitivity to INT in females. The results point to the important roles that fathers play in child INT and EXT behaviors and important differences between males and females. (PsycINFO Database Record


In vitro biotransformation of red ginseng extract by human intestinal microflora: metabolites identification and metabolic profile elucidation using LC-Q-TOF/MS.
Ginseng is an important and widely used herbal medicine in Asia and has gained popularity in the western countries. Ginseng products are usually administered orally, after which their complicated components are brought into contact with intestinal microflora in the alimentary tract and metabolized. The metabolic investigation of ginseng in intestinal tract is necessary for elucidating its pharmacological activities. However, most of the reports about the metabolism of ginseng with intestinal microflora are focused on single ginseng saponin with the whole action of ginseng extract ignored. In the present paper, in vitro biotransformation of red ginseng extract by human intestinal microflora was conducted, and a rapid liquid chromatography with time-of-flight mass spectrometry (LC-Q-TOF/MS) method was used for rapid identification of the metabolites and metabolic profile of ginseng saponins. A total of 37 ginseng saponins in red ginseng extract were characterized, 17 of which were assessed to be metabolized by human intestinal microflora. Also, 30 metabolites, mostly deglycosylated, were detected and identified in the biotransformed red ginseng extract, including 4 original ingredients of red ginseng, 6 ginsenoside lactate esters, and 2 glycosylated metabolites. The metabolic profile of ginseng saponins biotransformed by human intestinal microflora was elucidated based on the metabolite information. The results indicated that deglycosylation was the major metabolic pathway of saponins in red ginseng. The esterification and glycosylation reaction also occurred during the biotransformation. Our study indicated that there was some differences in the biotransformation of single ginseng saponin and red ginseng extract. It must be noted that the ginsenoside lactate esters were firstly found in the metabolites of ginsenosides.


CA19-9 as a Predictor of Worse Clinical Outcome in Medullary Thyroid Carcinoma.
Medullary thyroid carcinoma (MTC) is a rare disease, and its classic tumor marker is calcitonin. However, recently, very aggressive cases have been reported to also secrete carbohydrate antigen 19-9 (CA19-9), and its role as a marker of worse prognosis has been questioned. The aim of this study was to analyze the relationship between CA19-9 serum levels and MTC outcomes. We retrospectively reviewed 122 MTC patients followed in a tertiary cancer center from 1985 to 2017. Clinical-pathologic characteristics, therapeutic approaches, and outcomes were recorded and CA19-9 was collected. Of the 122 patients included in the study, 48 had distant metastases, and at the end of follow-up 18.1% had structural persistent disease and 32.7% had progressive disease. CA19-9 was significantly higher in those who had disease progression than in those who had not (21.4 [14.3-110.9] vs. 7.27 [0.6-44.75] U/mL, p = 0.01) and was also higher in patients who died from MTC (18.4 [14.3-110.9] vs. 7.59 [0.6-67.8] U/mL, p < 0.001). Furthermore, using a ROC curve analysis, the cutoff point for CA19-9 in MTC patients was lower than that observed in pancreatic tumors. CA19-9 might have a role as a prognostic factor in addition to calcitonin and carcinoembryonic antigen in metastatic MTC.