Provider-patient interaction in diabetes care: effects on patient self-care and outcomes. A systematic review.
A systematic review of the research literature using Medline, Embase, Psyclit/Psycinfo and the Cochrane Library files 1980 through 2001, identified only eight publications based on well-designed studies involving randomised controlled trials (RCTs)--testing the effects of modification of provider-patient interaction and provider consulting style on patient diabetes self-care and diabetes outcomes, in general practice or hospital outpatient settings. Review of these publications leads to the tentative conclusion that focusing on patient behaviour--directly enhancing patient participation i.e. by assistant-guided patient preparation for visits to doctors, empowering group education, group consultations, or automated telephone management--is more effective than focusing on provider behaviour to change their consulting style into a more patient-centred one. The latter proves hard to sustain, needs intensive support, and is not very effective in improving patient self-care and health outcomes when executed alone. Patient behaviour focused interventions show good efficacy and efficiency, and improve patient self-care and diabetes outcomes. More well-designed intervention studies focusing on enhancing patient participation in primary and hospital outpatient diabetes care are needed.


Excessive weight gain in primigravidas with low-risk pregnancy: selected obstetric consequences.
To determine whether a group of normal weight women with a low-risk pregnancy who increased their prepregnant weight by more than 25% experienced a longer second stage of labor or a higher proportion of operative deliveries than a group of normal weight women who increased their prepregnant weight by 25% or less. Comparative, descriptive, retrospective chart review. A 480-bed tertiary care medical center. One hundred four primigravidas who had normal weight for height at conception and who experienced low-risk pregnancy. Length of second stage labor and mode of delivery. A statistically significant difference was found in the mean length of second stage labor between the two groups, t(94) = -2.05, p = 0.02. A higher proportion of operative deliveries (vacuum, forceps, or cesarean section) occurred in the group that increased their prepregnant weight by more than 25%, chi 2(3, N = 104) = 15.87, p = 0.001. The amount of weight gained during pregnancy influences progress and intervention during the second stage of labor.


Stathmin expression and its relationship to microtubule-associated protein tau and outcome in breast cancer.
Microtubule-associated proteins (MAPs) endogenously regulate microtubule stability. Here, the prognostic value of stathmin, a destabilizing protein, was assessed in combination with MAP-tau, a stabilizing protein, in order to evaluate microtubule stabilization as a potential biomarker. Stathmin and MAP-tau expression levels were measured in a breast cancer cohort (n = 651) using the tissue microarray format and quantitative immunofluorescence (AQUA) technology, then correlated with clinical and pathological characteristics and disease-free survival. Univariate Cox proportional hazard models indicated that high stathmin expression predicts worse overall survival (hazard ratio [HR] = 1.48; 95% confidence interval [CI] = 1.119-1.966; P = .0061). Survival analysis showed 10-year survival of 53.1% for patients with high stathmin expression versus 67% for low expressers (log-rank, P < .003). Cox multivariate analysis showed high stathmin expression was independent of age, menopausal status, nodal status, nuclear grade, tumor size, and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression (HR = 1.19; 95% CI = 1.03-1.37; P = .01). The ratio of MAP-tau to stathmin expression showed a positive correlation to disease-free survival (HR = 0.679; 95% CI = 0.517-0.891; P = .0053) with a 10-year survival of 65.4% for patients who had a high ratio of MAP-tau to stathmin versus 52.5% 10-year survival rate for those with a low ratio (log-rank, P = .0009). Cox multivariate analysis showed the ratio of MAP-tau to stathmin was an independent predictor of overall survival (HR = 0.609; 95% CI = 0.422-0.879; P = .008). Low stathmin and high MAP-tau are associated with increased microtubule stability and better prognosis in breast cancer.


A comparison between single-incision and conventional laparoscopic cholecystectomy.
Single-incision laparoscopic surgery is becoming a more widely accepted surgical approach. However, the feasibility and safety of single-incision laparoscopic cholecystectomy (SILC) are yet to be established. The present study compared outcomes following the use of SILC or conventional laparoscopic cholecystectomy (CLC) on patients with gallbladder disease. The study involved 190 symptomatic gallbladder disease patients treated between March 2009 and February 2011. Ninety-six patients underwent SILC, and 94 patients underwent CLC. Clinical and surgical outcomes were compared. The SILC and CLC groups were similar in terms of age, gender ratio, body mass index, and diagnoses. The two groups were also found to be similar in terms of postoperative clinical course and complications. The SILC group had a longer operation time, less postoperative pain, and a shorter hospital stay than the CLC group (P<.05 for all variables). SILC using the OCTO port system (Darim Corp., Korea) was as safe and feasible as CLC. Additionally, SILC is less invasive and more comfortable for patients than CLC.


The constituent tryptophans and bisANS as fluorescent probes of the active site and of a secondary binding site of stromelysin-1 (MMP-3).
The active site of the catalytic domain of stromelysin-1 (matrix metalloproteinase-3, MMP-3) was probed by fluorescence quenching, lifetime, and polarization of its three intrinsic tryptophans and by the environmentally sensitive fluorescent reporter molecule bisANS. Wavelength-dependent acrylamide quenching identified three distinct emitting tryptophan species, only one of which changes its emission and fluorescence lifetime upon binding of the competitive inhibitor Batimastat. Significant changes in the tryptophan fluorescence polarization occur upon binding by any of the three hydroxamate inhibitors Batimastat, CAS108383-58-0, and Celltech CT1418, all of which bind in the P2'-P3' region of the active site. In contrast, the inhibitor CGS27023A, which is thought to bind in the P1-P1' region, does not induce any change in tryptophan fluorescence polarization. The use of the fluorescent probe bisANS revealed the existence of an auxiliary binding site extrinsic to the catalytic cleft. BisANS acts as a competitive inhibitor of stromelysin with a dissociation constant of Ki=22 microM. In addition to this binding to the active site, it also binds to the auxiliary site with a dissociation constant of 3.40+/-0.17 microM. The auxiliary site is open, hydrophobic, and near the fluorescing tryptophans. The binding of bisANS to the auxiliary site is greatly enhanced by Batimastat, but not by the other competitive inhibitors tested.


Fish faeces and ocean life: Better understanding marine carbon cycles could inform sustainable fishing policies: Better understanding marine carbon cycles could inform sustainable fishing policies.
Better knowledge of marine carbon cycles, their effect on global warming, and the important role of fish in both, can convince politics to establish more sustainable fishery policies.


DSLET and ACTH(4-10) increase mitotic activity of hepatocytes and suppress antibody production.
The mitotic index of hepatocytes remained unchanged after 10 intraperitoneal injections of DSLET and ACTH(4-10) in doses of 0.5, 1.5, and 5 microg/kg, but increased after injection of these substances in doses of 50 and 150 microg/kg. DSLET in doses of 5, 50, and 150 microg/kg decreased the number of antibody-producing cells in the spleen. ACTH(4-10) possessed immunosuppressive activity not only in these doses, but also in a dose of 1.5 microg/kg. As differentiated from mitotic activity of hepatocytes, the degree of immunosuppression increased with increasing the dose of test peptides.


Utilization of diagnostic resources and costs in patients with suspected cardiac chest pain.
Non-acute chest pain is a common complaint and can be caused by various conditions. With the rising healthcare expenditures of today, it is necessary to use our healthcare resources effectively. This study aims to give insight into the diagnostic effort and costs for patients with non-acute chest pain. Financial data of patients without a cardiac history from four hospitals (January 2012-October 2018), who were registered with the national diagnostic code 'no cardiac pathology' (ICD-10 Z13.6), 'chest wall syndrome' (ICD-10 R07.4), or 'stable angina pectoris' (ICD-10 I20.9) were extracted. In total, 74 091 patients were included for analysis and divided into the following final diagnosis groups: no cardiac pathology: N = 19 688 (age 53 ± 18), 46% male; chest wall syndrome: N = 40 858 (age 56 ± 15), 45% male; and stable angina pectoris (AP): N = 13 545 (age 67 ± 11), 61% male. A total of approximately €142.7 million was spent during diagnostic work-up. The total expenditure during diagnostic effort was €1.97, €8.13, and €10.7 million, respectively for no cardiac pathology, chest wall syndrome, and stable AP per year. After 8 years of follow-up, ≥95% of the patients diagnosed with no cardiac pathology or chest wall syndrome had an (cardiac) ischaemic-free survival. The diagnostic expenditure and clinical effort to ascertain non-cardiac chest pain are high. We should define what we as society find acceptable as 'assurance costs' with an increasing pressure on the healthcare system and costs.


Topical delivery of mitogen-activated protein kinase inhibitor binimetinib prevents the development of cutaneous neurofibromas in neurofibromatosis type 1 mutant mice.
Cutaneous neurofibromas (cNFs) are a hallmark of patients with the neurofibromatosis type 1 (NF1) genetic disorder. These benign nerve sheath tumors, which can amount to thousands, develop from puberty onward, often cause pain and are considered by patients to be the primary burden of the disease. Mutations of NF1, encoding a negative regulator of the RAS signaling pathway, in the Schwann cell (SCs) lineage are considered to be at the origin of cNFs. The mechanisms governing cNFs development are poorly understood, and therapeutics to reduce cNFs are missing, mainly due to the lack of appropriate animal models. To address this, we designed the Nf1-KO mouse model that develops cNFs. Using this model, we found that cNFs development is a singular event and goes through 3 successive stages: initiation, progression, and stabilization characterized by changes in the proliferative and MAPK activities of tumor SCs. We found that skin trauma accelerated the development of cNFs and further used this model to explore the efficacy of the MEK inhibitor binimetinib to cure these tumors. We showed that while topically delivered binimetinib has a selective and minor effect on mature cNFs, the same drug prevents their development over long periods.


A novel cobalt(II) coordination polymer containing the fumarate anion and o-phenanthroline.
The self-assembly of three crystallographically distinct fumarate ions, two unique cobalt(II) ions and two unique o-phenanthroline molecules results in a two-dimensional polymeric structure with the formula [Co(2)(C(4)H(2)O(4))(2)(C(12)H(8)N(2))(2)](n), namely di-mu-fumatato-bis(o-phenanthroline)dicobalt(II). The Co atoms are at the nodes of a two-dimensional array linked by coordinated fumarate ligands. Each Co atom is coordinated in a distorted octahedral manner to four fumarate O atoms and two N atoms from the chelating phenanthroline ligands.


Building physician resilience.
To explore the dimensions of family physician resilience. Qualitative study using in-depth interviews with family physician peers. Hamilton, Ont. Purposive sample of 17 family physicians. An iterative process of face-to-face, in-depth interviews that were audiotaped and transcribed. The research team independently reviewed each interview for emergent themes with consensus reached through discussion and comparison. Themes were grouped into conceptual categories. Four main aspects of physician resilience were identified: 1) attitudes and perspectives, which include valuing the physician role, maintaining interest, developing self-awareness, and accepting personal limitations; 2) balance and prioritization, which include setting limits, taking effective approaches to continuing professional development, and honouring the self;3) practice management style, which includes sound business management, having good staff, and using effective practice arrangements; and 4) supportive relations, which include positive personal relationships, effective professional relationships, and good communication. Resilience is a dynamic, evolving process of positive attitudes and effective strategies.


Actin and calmodulin coexist in the equatorial segment of ejaculated boar sperm.
The direct overlay technique with iodinated calmodulin on boar sperm fractions evidenced a strong bond in the 45,000 molecular weight, which is the region recognized by anti-actin antibodies. This result and the close codistribution of the two staining patterns for calmodulin and actin with immunofluorescence and immunoelectronmicroscopy suggest a possible interaction between calmodulin and actin in boar sperm.


Computational study of kinematics of the anterior cruciate ligament double-bundle structure during passive knee flexion-extension.
The anterior cruciate ligament (ACL) comprises an anteromedial bundle (AMB) and posterolateral bundle (PLB). Cadaver studies showed that this double-bundle structure exhibits reciprocal function during passive knee flexion-extension, with the PLB taut in knee extension and the AMB taut in knee flexion. In vivo measurements indicated that straight-line lengths of both bundles decrease with increasing knee-flexion angle (KFA). To interpret these seemingly conflicting facts, we developed a computational ACL model simulating the kinematics of the double-bundle structure during passive knee flexion-extension. Tibial and femoral shapes were reconstructed from computed-tomography images of a cadaver knee and used to construct an idealized model of an ACL including its bundles at the tibiofemoral joint. The ACL deformations at various KFAs were computed by finite element analysis. Results showed that the PLB was stretched in knee extension (KFA = 0∘) and slackened with increasing KFA. The AMB was stretched in knee extension (KFA = 0∘) and remained stretched on the medial side when the knee flexed (KFA = 90∘), but its straight-line length decreased with increasing KFA. These findings are consistent with cadaver and in vivo experimental results and highlight the usefulness of a computational approach for understanding ACL functional anatomy.


Validity of International Classification of Diseases, Tenth Revision, Codes for Cirrhosis.
Accurate identification of patients with cirrhosis is important for research using administrative databases. We aimed to examine the accuracy of several major ICD-10 codes for cirrhosis diagnosis in a large and diverse patient cohort; there is little existing research on this topic. Using data from 3,396 patients with chronic liver disease (hepatitis B or C or nonalcoholic fatty liver disease) from 1 university and several community medical centers, we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value, and area under the receiver operating characteristic curve (AUROC) for several major ICD-10 codes for cirrhosis, which was verified by individual chart review. We performed a secondary validation in a general cohort of 1,560 randomly selected patients. While each of the individual study ICD-10 codes were specific (98.08-100%), none of the codes were sufficiently sensitive (0.27-55.70%). PPVs were high in the chronic liver disease cohort (88.41-100%) but lower in the general population (55.53-66.76%). The AUROC for having at least 1 code was higher (0.79) than any code alone (0.50-0.65). Individual ICD-10 codes are suboptimal for identifying patients with cirrhosis in the general patient population. We recommend conditioning ICD-10 code searches with a chronic liver disease diagnosis code and/or combining diagnostic codes to maximize performance.


Fetal, neonatal, and infant microbiome: Perturbations and subsequent effects on brain development and behavior.
The human gastrointestinal tract harbors a diverse and complex community of microbes, termed gut microbiota, that normally assemble during the first postnatal years of life. This evolution-driven process has been shown to contribute to the developmental programming of epithelial barrier function, gut homeostasis, and angiogenesis, as well as the development and function of the immune system. Research over the last few years has revealed that the actions of the gut microbiota have much wider effects on host physiology and development than originally believed, including the modulation of brain development and behavior. This article briefly reviews recent findings on the impact of the gut microbiota on brain development, and how disturbances in the assembly and maturation of the gut microbiota may impact development of motor, social, and cognitive functions. The potential link between microbiota and metabolic requirements of the developing brain is also considered.


Comparison of ruminant and human attaching and effacing Escherichia coli (AEEC) strains.
The presence of 12 genes associated with virulence in human attaching and effacing Escherichia coli (AEEC) was studied within a collection of 20 enterohemorrhagic E. coli (EHEC) and 206 atypical enteropathogenic E. coli (EPEC) isolated from ruminants. In addition, virulence genes and the clonal relationship of 49 atypical EPEC O26 strains isolated from humans and ruminants were compared to clarify whether ruminants serve as a reservoir of atypical EPEC for humans. A great diversity in the content of virulence gene was found. Thus, the espH, espG and map genes were detected in more than 85% of ruminant AEEC strains; the tccP2, espI, efa1/lifA, ehxA and paa genes were present in 50-70% of strains; and other genes such as tccP, espP, katP and toxB were detected in <25% of strains. EHEC strains contained more virulence genes than atypical EPEC strains. Our results suggest for the first time that the efa1/lifA gene is associated with diarrhea in newborn ruminants and that the AEEC strains with the H11 flagellar antigen are potentially more virulent than the non-H11 AEEC strains. Importantly, we identified a new intimin variant gene, eaeρ, in three ruminant atypical EPEC strains. The comparison of ruminant and human EPEC O26 strains showed that some ruminant strains possess virulence gene profiles and pulse-field gel electrophoresis pulsotypes similar to those of human strains. In conclusion, our data suggest that atypical EPEC is a heterogeneous group with different pathogenic potential and that ruminants could serve as a reservoir of atypical EPEC for humans.


Sonographic diagnosis of acute appendicitis: interpretive pitfalls.
Graded compression sonography has proven to be of significant clinical value in the assessment of patients with right lower quadrant pain and possible appendicitis [1-3]. Despite its proven utility, a number of imaging pitfalls must be kept in mind when sonograms of the right lower quadrant are interpreted. The purpose of this pictorial essay is to illustrate a number of important limitations and areas of interpretive difficulty in sonography for appendicitis.


Distinct Roles of Ventromedial versus Ventrolateral Striatal Medium Spiny Neurons in Reward-Oriented Behavior.
The ventral striatum (VS) is a key brain center regulating reward-oriented behavior [1-4]. The VS can be anatomically divided into medial (VMS) and lateral (VLS) portions based on cortical input patterns. The VMS receives inputs from medial pallium-originated limbic structures (e.g., the medial prefrontal cortex [mPFC]), and the VLS receives inputs from the lateral pallium-originated areas (e.g., the insula) [5, 6]. This anatomical feature led us to hypothesize a functional segregation within the VS in terms of the regulation of reward-oriented behavior. Here, we engineered a fiber photometry system [4] and monitored population-level Ca2+ activities of dopamine D2-receptor-expressing medium spiny neurons (D2-MSNs), one of the major cell types in the striatum, during a food-seeking discrimination task. We found that VLS D2-MSNs were activated at the time of cue presentation. In stark contrast, VMS D2-MSNs were inhibited at this time point. Optogenetic counteraction of those changes in the VLS and VMS impaired action initiation and increased responding toward non-rewarded cues, respectively. During lever-press reversal training, VMS inhibition at the time of cue presentation temporarily ceased and optogenetic activation of VMS D2-MSNs facilitated acquisition of the new contingency. These data indicate that the opposing inhibition and excitation in VMS and VLS are important for selecting and initiating a proper action in a reward-oriented behavior. We propose distinct subregional roles within the VS in the execution of successful reward-oriented behavior.


The penetration of Fasciola hepatica miracidia into the snail host Fossaria bulimoides. A scanning electron microscope study.
Snails of the species Fossaria bullimoides were exposed to miracidia of Fasciola hepatica for given periods of time. The course of penetration was followed by means of scanning electron microscopy. Topographical features of miracidial morphology were studied with emphasis on epidermal plates and body shape. Comparisons are made on the rate of penetration into this snail host.


Federated analysis of BRCA1 and BRCA2 variation in a Japanese cohort.
More than 40% of the germline variants in ClinVar today are variants of uncertain significance (VUSs). These variants remain unclassified in part because the patient-level data needed for their interpretation is siloed. Federated analysis can overcome this problem by "bringing the code to the data": analyzing the sensitive patient-level data computationally within its secure home institution and providing researchers with valuable insights from data that would not otherwise be accessible. We tested this principle with a federated analysis of breast cancer clinical data at RIKEN, derived from the BioBank Japan repository. We were able to analyze these data within RIKEN's secure computational framework without the need to transfer the data, gathering evidence for the interpretation of several variants. This exercise represents an approach to help realize the core charter of the Global Alliance for Genomics and Health (GA4GH): to responsibly share genomic data for the benefit of human health.


Association of cigarette smoking with retinal capillary plexus: an optical coherence tomography angiography study.
To investigate the association between cigarette smoking and retinal capillary plexus (RCP) using optical coherence tomography angiography (OCTA) and to examine whether potential vascular risk factors could impact their association. This is a cross-sectional, community-based study. The Jidong Eye Cohort Study included participants aged ≥18 years in the Jidong community (Tangshan city, northern China) from August 2019 to January 2020. All participants underwent comprehensive ophthalmic examination and completed detailed smoking questionnaires. Retinal vessel density in the superficial and deep RCP was automatically measured using OCTA. Of the 2598 participants included in the study, 2026 (78.0%) never smoked and 572 (22.0%) had a history of smoking (494 [19.0%] current smokers and 78 [3.0%] former smokers). The median (interquartile range) age was 41 (34-52) years for the non-smoking group and 45 (35-54.5) years for the smoking group. Multivariable analysis showed that smoking history is associated with a low deep RCP vessel density in the parafovea (β, -0.53; 95% confidence interval [CI], -0.82 to -0.24) and four quadrants. Increased smoking pack-years were associated with reduced deep RCP vessel density in the parafovea (p for trend <0.001) and four quadrants. The significant interaction between diabetes and smoking only was found for superficial RCP vessel density in the parafovea (p for interaction = 0.014) and four quadrants except for the temporal quadrants. Cigarette smoking is an independent risk factor for reduced deep RCP vessel density. Our findings imply the potential detrimental effect of smoking on the occurrence of ocular diseases.


Primary osteosarcoma of kidney with liposarcomatous elements.
Extraosseous osteogenic sarcomas are unusual tumors that are seldom diagnosed. Although primary renal osteogenic sarcoma has been reported, and is described in the Armed Forces Institute of Pathology fascicle, most clinicians are unaware of its existence. We describe a patient with this disease to remind clinicians of this tumor, its presentation and rapid evolution.


Quantum engineering: an atom-sorting machine.
Laser cooling and trapping techniques allow us to control and manipulate neutral atoms. Here we rearrange, with submicrometre precision, the positions and ordering of laser-trapped atoms within strings by manipulating individual atoms with optical tweezers. Strings of equidistant atoms created in this way could serve as a scalable memory for quantum information.


Calcium channel modulators: effects on gastric function.
Calcium is important in stimulus-secretion coupling in the gut. We therefore examined a dihydropyridine (nitrendipine), a phenylalkylamine (verapamil) and a benzothiazepine (diltiazem) calcium channel blocker as well as a calcium channel 'agonist', CGP 28392, in several models of gastric function. Nitrendipine significantly decreased stress-induced gastric lesions, but was far less efficacious against 100% ethanol-induced lesions. The anti-ulcer effects of nitrendipine were not reversible with indomethacin, sodium meclofenamate or N-ethylmaleimide. Nitrendipine also significantly reduced basal gastric acid output. Verapamil significantly reduced stress lesions in an indomethacin and meclofenamate-reversible manner, but worsened ethanol ulcers. Verapamil also decreased basal acid secretion. Diltiazem decreased stress lesions (indomethacin- and meclofenamate-reversible), worsened ethanol lesions and slightly reduced acid secretion. CGP 28392 exerted a modest stress gastroprotective effect, decreased ethanol lesions and reduced slightly basal acid secretion. A possible clinical role for gastric calcium channel blockade is raised by these results.


Back stabber: ladder fall causing traumatic aortic transection.
A 68-year-old man presented with back pain after falling from a ladder and was found to have anterolisthesis of thoracic vertebrae T11-12 with secondary focal aortic injury and disruption of the aortic wall. This was successfully repaired using thoracic endovascular aortic repair (TEVAR) followed by spinal fusion with excellent result.


Antioxidant enzyme activity in rat hippocampus after chronic and acute stress exposure.
Chronic exposure to stress alters the prooxidant-antioxidant balance, which might lead to the development of various human pathological states. In order to explain the role of antioxidant response in stress-induced injury, we examined the effects of two types of acute stress, as well as combined effects of chronic and acute stress on manganese-superoxide dismutase, copper,zinc-superoxide dismutase, and catalase activities in rat brain hippocampus. Our results show that chronic stress induces an increase in oxidative enzyme activities and that adaptation to chronic stress might alter hippocampal antioxidant mechanisms' response to acute stress.


Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response.
Cells of the innate and adaptive immune systems are the progeny of a variety of haematopoietic precursors, the most primitive of which is the haematopoietic stem cell. Haematopoietic stem cells have been thought of generally as dormant cells that are only called upon to divide under extreme conditions, such as bone marrow ablation through radiation or chemotherapy. However, recent studies suggest that haematopoietic stem cells respond directly and immediately to infections and inflammatory signals. In this Review, we summarize the current literature regarding the effects of infection on haematopoietic stem cell function and how these effects may have a pivotal role in directing the immune response from the bone marrow.


Enrichment of measles virus-like RNA in the nucleocapsid fraction isolated from subacute sclerosing panencephalitis brains.
A procedure has been developed which facilitates the detection of measles virus RNA sequences in human brains. The procedure involves isolating subviral components (nucleocapsids) from brain tissues prior to RNA purification, followed by hybridization of these RNAs to cDNA synthesized from measles virus 50 S RNA template. Using these techniques we were able to obtain an RNA fraction which was manyfold enriched in measles virus-specific RNA, relative to unfractionated subacute sclerosing panencephalitis (SSPE) brain RNAs 70-100% of the measles virus-specific RNA present these SSPE brain samples were recovered in this enriched fraction.


Environmental impacts of waste management and valorisation pathways for surplus bread in Sweden.
Bread waste represents a significant part of food waste in Sweden. At the same time, the return system established between bakeries and retailers enables a flow of bread waste that is not contaminated with other food waste products. This provides an opportunity for alternative valorisation and waste management options, in addition to the most common municipal waste treatment, namely anaerobic digestion and incineration. An attributional life cycle assessment of the management of 1 kg of surplus bread was conducted to assess the relative environmental impacts of alternative and existing waste management options. Eighteen impact categories were assessed using the ReCiPe methodology. The different management options that were investigated for the surplus bread are donation, use as animal feed, beer production, ethanol production, anaerobic digestion, and incineration. These results are also compared to reducing the production of bread by the amount of surplus bread (reduction at the source). The results support a waste hierarchy where reduction at the source has the highest environmental savings, followed by use of surplus bread as animal feed, donation, for beer production and for ethanol production. Anaerobic digestion and incineration offer the lowest environmental savings, particularly in a low-impact energy system. The results suggests that Sweden can make use of the established return system to implement environmentally preferred options for the management of surplus bread.


Within- and among-population level differences in response to chronic copper exposure in southern toads, Anaxyrus terrestris.
Environmental contaminants are implicated in the global decline of amphibian populations. Copper (Cu) is a widespread contaminant that can be toxic at concentrations just above the normal physiological range. In the present study we examined the effects of chronic Cu aqueous exposure on embryos and larvae of southern toads, Anaxyrus (Bufo) terrestris. Measurable levels of Cu were found in larvae, with tissue concentrations up to 27.5 μg Cu/g dry mass. Aqueous concentrations of Cu as low as 10 μg/L significantly reduced survival to the free-swimming stage and no larvae reached metamorphosis at concentrations above 15 μg/L. Clutches from populations with prior Cu exposure had the lowest survivorship. Among several populations there was significant variation in survivorship at different levels of Cu. More data are needed to understand the underlying causes of within- and among-population resilience to anthropogenic stressors.


Inhibitors of apoptosis proteins in prostate cancer cell lines.
The caspases are the central executioners of apoptosis. The inhibitors of apoptosis proteins (IAPs) are a family of recently described caspase inhibitors. We hypothesised that tumor resistance to apoptosis could be due in part to IAP expression. The expression of NAIP, cIAP-1, cIAP-2, XIAP, and survivin was investigated in the prostate cancer cell lines LNCaP, PC3, and DU145. RNase protection assays and Western blotting were used to assess RNA and protein expression. Apoptotic susceptibility was determined using etoposide and assessed by propidium iodide (PI) DNA incorporation using flow cytometry. DU145 and PC3 cells were more resistant to apoptosis than LNCaP cells. All the IAPs were identified in the cell lines with variation in IAP expression between different cell types. Immunohistochemistry demonstrated cIAP-1 expression in PC3 cells was nuclear, while the expression of cIAP-2 and XIAP was perinuclear. Growing LNCaP cells in charcoal-stripped or androgen-supplemented medium resulted in no alteration in IAP expression. This study characterises the expression of IAP in three of the most commonly used prostate cancer cells. IAP may make an important contribution to apoptotic resistance in patients with prostate cancer.


Glossopharyngeal schwannoma a rare case report: Diagnostic and surgical approach.
Schwannomas are tumors of the nerve sheath that consist of Schwann cells that are often described as slow-growing. Glossopharyngeal schwannomas are rare tumors present in the region of the posterior fossa, with limited case reports present in literature. While patients may present asymptomatically, some present with vestibulocochlear symptoms or lower cranial nerve dysfunction. We report an extremely rare case of a left para-pharyngeal carotid space glossopharyngeal schwannoma in a 26-year-old female. The presentation was a 3-month left sided neck swelling and a hoarse voice. Radiological investigations were completed (neck ultrasound; CT; MRI scans). Investigations revealed a solid lesion measuring about 29 × 10 mm. The final decision was to excise the mass under microsurgery. CN 9-11 schwannomas are often called jugular foramen schwannomas. Intraoperatively, these get differentiated as glossopharyngeal schwannomas. Diagnosis involves a physical examination, a detailed history, audiological assessments, and radiological investigations. While MRI scans are known as the most effective pre-operative diagnostic test, cases are in majority discovered intra-operatively. Surgical excision is the recommended approach. Post-operative recurrence is rare. Pre-operative diagnosis is often difficult due to the rarity and similarly presenting differential diagnoses. Schwannomas of the glossopharyngeal nerve are extremely rare tumors that may present with lower cranial nerve or vestibulocochlear deficits. Magnetic resonance imaging is a useful tool in diagnosing this unordinary tumor. This case report intends to provide further data regarding the clinical presentation, the patient population, and the diagnostic and surgical approach in dealing with this incredibly rare tumor.


Propofol for sedation in neuro-intensive care.
Interventions in the intensive care unit often require that the patient be sedated. Propofol is a widely used, potent sedative agent that is popular in critical care and operating room settings. In addition to its sedative qualities, propofol has neurovascular, neuroprotective, and electroencephalographical effects that are salutory in the patient in neurocritical care. However, the 15-year experience with this agent has not been entirely unbesmirched by controversy: propofol also has important adverse effects that must be carefully considered. This article discusses and reviews the pharmacology of propofol, with specific emphasis on its use as a sedative in the neuro-intensive care unit. A detailed explanation of central nervous system and cardiovascular mechanisms is presented. Additionally, the article reviews the literature specifically pertaining to neurocritical care use of propofol.


PCSK9 inhibitor therapy in homozygous familial defective apolipoprotein B-100 due to APOB R3500Q: A case report.
Identification of a patient homozygous for familial defective apolipoprotein B-100(FDB) and successful treatment with PCSK9 inhibition.


A review of computational modeling and deep brain stimulation: applications to Parkinson's disease.
Biophysical computational models are complementary to experiments and theories, providing powerful tools for the study of neurological diseases. The focus of this review is the dynamic modeling and control strategies of Parkinson's disease (PD). In previous studies, the development of parkinsonian network dynamics modeling has made great progress. Modeling mainly focuses on the cortex-thalamus-basal ganglia (CTBG) circuit and its sub-circuits, which helps to explore the dynamic behavior of the parkinsonian network, such as synchronization. Deep brain stimulation (DBS) is an effective strategy for the treatment of PD. At present, many studies are based on the side effects of the DBS. However, the translation from modeling results to clinical disease mitigation therapy still faces huge challenges. Here, we introduce the progress of DBS improvement. Its specific purpose is to develop novel DBS treatment methods, optimize the treatment effect of DBS for each patient, and focus on the study in closed-loop DBS. Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.


The traditional uses, phytochemistry, pharmacology and toxicology of Cinnamomi ramulus: a review.
Cinnamomi ramulus (called Guizhi in Chinese) is a traditional medicine used to treat gastrointestinal dysfunction, cancer, arthritis, osteoporosis, spleen deficiency, Alzheimer's disease and obesity. This review aimed to provide a systematic summary on the geographical distribution, botany, traditional application, phytochemistry, pharmacology, pharmacokinetics, toxicology and other aspects of Cinnamomi ramulus. So far, more than 121 chemical compounds have been isolated from Cinnamomi ramulus, including volatile oil, organic acids, triterpenoid saponins, coumarins, tannins, flavonoids and flavonoid glycosides, steroids and polysaccharides. This paper reviews the pharmacological effects of Cinnamomi ramulus on antibacterial, anti-inflammatory, antiviral, antitumour, antipyretic and analgesic, antidiabetic and antiplatelet aggregation effects. Furthermore, the present review also indicates that Cinnamomi ramulus has the potential to develop into drugs for treating various diseases with high efficacy and low toxicity. The convictive evidence from modern pharmacology research supports the traditional application of Cinnamomi ramulus. However, further studies on the structure-activity relationship of some of the isolated compounds may improve their biological potency. More toxicological studies will also contribute to the progress of clinical trial studies.


Outcomes after tongue-lip adhesion or mandibular distraction osteogenesis in infants with Pierre Robin sequence and severe airway obstruction.
The objective was to review and compare outcomes after tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) in infants with severe breathing difficulties related to Pierre Robin sequence (PRS). A single-centre retrospective (2002-2012) study was carried out; 18 infants with severe breathing difficulties related to PRS resistant to conservative treatment, who underwent TLA or MDO to correct airway obstruction, were enrolled. The primary outcome measures were successful weaning from respiratory support and resumption of full oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who underwent MDO and all those treated with TLA were successfully weaned from respiratory support. After discharge, residual respiratory distress was diagnosed more commonly after TLA than after MDO (6/9 vs 1/9, P=0.050). Infants resumed oral feeding sooner after MDO than after TLA (mean days after surgery to full oral feeds 44±24 vs 217±134, P<0.003). The length of hospital stay was longer for infants treated with MDO than for those treated with TLA. The rate of complications was similar. Infants with severe airway obstruction related to PRS can benefit safely from either TLA or MDO. Although MDO lengthens the time to discharge, this option stabilizes airway patency of infants with PRS more efficiently and achieves full oral feeding more rapidly than TLA.


Hypercalcemia induced by prostaglandin E2 in thyroparathyroidectomized but not intact rats.
Prostaglandin E2 was infused into thoracic aorta of thyroparathyroidectomized (TPTX) and intact rats. Circulating calcium increased significantly in the TPTX group by 30 minutes and reached an increment of 1.5 +/- 0.21 mg/dl (x +/- SE, p less than .001) by 90 minutes. No calcium increments were observed in the intact rats. It is postulated that prior failures to demonstrate hypercalcemia during PGE2 infusion may have been due to calcitonin counterregulation.


Radial artery diameterand and age related functional maturation of the radio-cephalic arteriovenous fistula.
Previous studies have not described the relationship between reducing radial artery diameter as well as increasing age and functional maturation of the radio-cephalic arteriovenous fistula (RCAVF) and no data identify these as linear relationship. The objective of this study was to perform trend analysis to assess these aspects. Our retrospective cohort study enrolled and analyzed 353 follow-up cases that underwent first AVF creation. The artery and vein sizes were measured by ultrasound. We performed follow-up, a minimum of 3 months after surgery. Multivariable logistic regression analysis was used to identify independent risk factors inmaturation. Participant age was categorized into four groups (age ≤ 29, 30-49, 50-69, and 70-90 years). Radial artery diameter was categorized into four groups (≤ 1.9, >1.9 and ≤ 2.1, >2.1 and ≤ 2.4, >2.4 mm) according to median and interquartile ranges. We adjusted for confounders in four logistic models, and primary analyses were based on building ordered category models and tested P values for trends to estimate the relationship of radial artery diameter and each 20-year increase in age with risk of maturation. The mature RCAVF group included 301 cases, and the immature group included 52 cases. Radial artery diameter, age, and diabetes were independent risk factors of maturation. Odds ratios (ORs) associated with maturation reduced with increasing age, while ORs increased with increasing radial artery diameter. P values for trends(<0.05) were observed in all four models. A reduction in radial artery diameter and higher age were significantly associated with a higher incidence of immaturity after adjusting the multivariate models. The risks of immaturation were increased by more than 1.54 fold for each 20-year increase and increased by more than 1.34 fold for the smaller radial artery diameter group. Our findings suggest that a significantly higher immaturity risk of RCAVF was associated with increasing age and a reduction in radial artery diameter. Our study identified a linear exposure-response relationship of age and radial artery diameter with immaturity incident. A careful selection of patients will be helpful in improving AVF functional maturation.


Maternal obesity and diabetes may cause DNA methylation alteration in the spermatozoa of offspring in mice.
The adverse effects on offspring of diabetic and/or obese mothers can be passed to the next generation. However, the mechanisms behind this are still unclear. Epigenetics may play a key role during this process. To confirm the hypothesis, we investigated the DNA methylation of several imprinted genes in spermatozoa of offspring from diabetic and/or obese mothers utilizing streptozotocin (STZ)- and high-fat-diet (HFD)-induced mouse models. We found that the DNA methylation of Peg3 was significantly increased in spermatozoa of offspring of obese mothers compared to that in spermatozoa of offspring of normal mothers. The DNA methylation of H19 was significantly higher in spermatozoa of offspring of diabetic mothers than that in spermatozoa of offspring of non-diabetic mothers. These results indicate that pre-gestational diabetes and/or obesity can alter DNA methylation in offspring spermatozoa.


Cartilage-like protein hydrogels engineered via entanglement.
Load-bearing tissues, such as muscle and cartilage, exhibit high elasticity, high toughness and fast recovery, but have different stiffness (with cartilage being significantly stiffer than muscle)1-8. Muscle achieves its toughness through finely controlled forced domain unfolding-refolding in the muscle protein titin, whereas articular cartilage achieves its high stiffness and toughness through an entangled network comprising collagen and proteoglycans. Advancements in protein mechanics and engineering have made it possible to engineer titin-mimetic elastomeric proteins and soft protein biomaterials thereof to mimic the passive elasticity of muscle9-11. However, it is more challenging to engineer highly stiff and tough protein biomaterials to mimic stiff tissues such as cartilage, or develop stiff synthetic matrices for cartilage stem and progenitor cell differentiation12. Here we report the use of chain entanglements to significantly stiffen protein-based hydrogels without compromising their toughness. By introducing chain entanglements13 into the hydrogel network made of folded elastomeric proteins, we are able to engineer highly stiff and tough protein hydrogels, which seamlessly combine mutually incompatible mechanical properties, including high stiffness, high toughness, fast recovery and ultrahigh compressive strength, effectively converting soft protein biomaterials into stiff and tough materials exhibiting mechanical properties close to those of cartilage. Our study provides a general route towards engineering protein-based, stiff and tough biomaterials, which will find applications in biomedical engineering, such as osteochondral defect repair, and material sciences and engineering.


Combined modality treatment with high-dose-rate brachytherapy boost for locally advanced prostate cancer.
This is a retrospective review of our experience using high-dose-rate (HDR) brachytherapy boost for prostate cancer. During the study period, we recommended external beam radiotherapy (45 Gy) and HDR boost (18 Gy in three fractions) combined with hormonal therapy (HT) for 2 months before and during radiotherapy to patients with at least one of the following risk features: pretreatment prostate-specific antigen>10, Gleason score (GS)>or=7, and clinical T3 disease. Additional HT for 2 years after radiotherapy was recommended for patients with GS>7. To patients whose risk of positive nodes exceeded 15%, we recommended whole pelvic radiotherapy. We administered HDR via single implant, and all fractions were given within 24h. This report is based on our initial 64 patients treated with HDR boost. The median follow-up was 50 months (range 25-68 months). The 4-year estimates of overall and disease-free survival were 98% and 92%, respectively. One patient experienced late grade 4 gastrointestinal toxicity. HDR brachytherapy is an effective means of delivering conformal prostate radiotherapy, and may be used with whole pelvic radiotherapy and HT.


Nephrectomy after radiofrequency ablation-induced ureteropelvic junction obstruction: potential complication and long-term assessment of ablation adequacy.
Little information is available concerning the morbidity of radiofrequency ablation (RFA) or the evolution of an RFA lesion over time. We report our findings in a kidney removed 1 year after RFA of a 2.3-cm renal tumor. After RFA, the patient experienced flank pain, followed by hydronephrosis, ureteropelvic junction obstruction, and eventual loss of function in the treated kidney. Nephrectomy revealed no residual renal cell carcinoma. RFA can completely destroy renal cell carcinoma in situ without histologic evidence of persistence or recurrence for up to 1 year after treatment. Care must be taken to avoid concurrent damage to the collecting system.


Exploring Mechanisms of Action in Exposure-Based Cognitive Behavioral Therapy for Eating Disorders: The Role of Eating-Related Fears and Body-Related Safety Behaviors.
Evidence-based cognitive behavioral therapy for eating disorders includes a component of exposure therapy, which involves patients confronting feared eating and body-related stimuli while preventing safety behaviors. With recent research demonstrating that eating-related fears and safety behaviors are central to eating disorder pathology, there is increased emphasis on improving the efficacy of exposure therapy in eating disorders. Doing so will require a better understanding of important mechanisms of action in this treatment. The present study explored how changes during treatment in eating-related fears and avoidance as well as body-related safety behaviors influence overall treatment outcomes. Individuals with eating disorders (N = 71) receiving exposure-based treatment completed measures of global eating disorder severity at admission and discharge. Hypothesized mechanisms of action were also assessed at admission and discharge as well as at a 2-week time point after beginning treatment. Path modeling analyses showed that decreased eating-related cognitions (feared concerns about eating) and emotions (anxiety about eating) at the 2-week time point were prospectively predictive of lowered global eating disorder symptom severity at discharge. Additionally, reduced body checking and avoidance behaviors after 2 weeks of treatment were also associated with lower eating disorder severity at discharge. These findings highlight the importance of exposure-based therapy in eating disorders and the need to uniquely address eating-related fears and safety behaviors.


Malaria parasites target the hepatocyte receptor EphA2 for successful host infection.
The invasion of a suitable host hepatocyte by mosquito-transmitted Plasmodium sporozoites is an essential early step in successful malaria parasite infection. Yet precisely how sporozoites target their host cell and facilitate productive infection remains largely unknown. We found that the hepatocyte EphA2 receptor was critical for establishing a permissive intracellular replication compartment, the parasitophorous vacuole. Sporozoites productively infected hepatocytes with high EphA2 expression, and the deletion of EphA2 protected mice from liver infection. Lack of host EphA2 phenocopied the lack of the sporozoite proteins P52 and P36. Our data suggest that P36 engages EphA2, which is likely to be a key step in establishing the permissive replication compartment.


Biomass-Derived Multilayer-Structured Microparticles for Accelerated Hemostasis and Bone Repair.
It is very desirable to develop advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications. Herein, biomass-derived multilayer-structured absorbable microparticles (MQ x T y ) composed of starches and plant polyphenols are readily constructed for the safe and effective treatment of bone defects with intractable bleeding by coating multiple layers of quaternized starch (Q+) and tannic acid onto microporous starch microparticles via facile layer-by-layer assembly. MQ x T y microparticles exhibit efficient degradability, low cytotoxicity, and good blood compatibility. Among various MQ x T y microparticles with distinct Q+/T- double layers, MQ2T2 with outmost polyphenol layer possess the unique properties of platelet adhesion/activation and red blood cell aggregation, resulting in the best hemostatic performance. In a mouse cancellous-bone-defect model, MQ2T2 exhibits the favorable hemostatic effect, low inflammation/immune responses, high biodegradability, and promoted bone repair. A proof-of-concept study of beagles further confirms the good performance of MQ2T2 in controlling intractable bleeding of bone defects. The present work demonstrates that such biomass-based multilayer-structured microparticles are very promising biomedical materials for clinical use.


Comparison of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with diabetes mellitus and non-ST-segment elevation myocardial infarction who underwent successful percutaneous coronary intervention.
Angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are known to be beneficial for either non-ST-segment elevation myocardial infarction (NSTEMI) patients or diabetes mellitus (DM) patients. However, the comparative efficacy of ACEI versus ARB in patients with NSTEMI and DM is unclear. The aim of this study was to compare the protective efficacy of ACEI versus ARB in patients with NSTEMI and DM, who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Among 53,281 patients enrolled in the nationwide Korea Acute Myocardial Infarction Registry, 3426 patients with NSTEMI and DM, who were treated with renin-angiotensin system (RAS) inhibitors, had undergone successful PCI with DESs. They were classified into two groups: ACEI group (N = 2076), and ARB group (N = 1350). Individual major clinical outcomes and major adverse cardiac events (MACE), the composite of total death, myocardial infarction (MI), and revascularization were compared between the two groups for up to two years. After propensity score-matching analysis, two propensity-matched groups (1103 pairs, total = 2206) were generated, and the baseline characteristics were balanced. Although all causes of death and recurrent MI were not different between the two groups, the incidence of revascularization (4.0% vs. 7.1%; p = 0.002), including target vessel (2.3% vs. 5.0; p = 0.002), and MACE (8.7% vs. 12.5%, p = 0.008), were lower in the ACEI group than the ARB group at two-year follow-up. Compared with ARB, no beneficial effects of ACEI on all causes of death, cardiac death, or recurrence of MI were observed, but ACEI reduced the incidence of revascularization and MACE in this population. Thus, well-designed trials with a larger population are needed to confirm these results.


Effects of MISA A on actin cytoskeleton of cultured HTM cells and intraocular pressure of rats and glaucomatous monkeys.
To determine the effects of misakinolide (MISA) A, which leads to the disassembly of actin filaments, on the actin cytoskeleton of cultured human trabecular meshwork (HTM) cells and on intraocular pressure (IOP) in living rats and monkeys. Cultured HTM cells were treated with MISA A, and the changes in the actin cytoskeleton were determined by immunofluorescence microscopy. Elevated IOP was induced in cynomolgus monkeys by unilateral laser photocoagulation of the trabecular meshwork (TM). The IOP response after topical administration of MISA A was determined in normotensive rats (Tonopen) and glaucomatous monkeys (pneumotonometer and Tonopen) at 0.5, 1, 2, 3, 4, 5, and 6 hr. MISA A caused dose- and time-dependent disruption of actin stress fibers in cultured HTM cells. Actin microfilaments and vinculin containing focal contacts deteriorated after 2 hr, 30 and 10 min of incubation with 5 nM, 10 nM, and 25 nM MISA A, respectively. Recovery was also dose- and time-dependent. The actin-disrupting effects were not reversible when the cells were incubated with MISA A at a low dose (10 nM) for 24 hr or a high dose (25 nM) for 30 min. Topical administration of MISA A significantly decreased IOP in rats by 5.8 +/- 0.5 (mean +/- SEM) (p < 0.05) Tonopen rat units. In monkeys, IOP was decreased by 3.8 +/- 0.5 mmHg (p < 0.001) in the normotensive eye and by 9.2 +/- 1.2 mmHg (p < 0.001) in the glaucomatous eye. MISA A greatly altered the actin cytoskeleton and cellular adhesions and reduced IOP, suggesting that MISA A may be a useful antiglaucoma strategy.


Pediatric trauma telemedicine in a rural state: Lessons learned from a 1-year experience.
Previous research from our center has shown that 27% of the pediatric trauma transfers from referring facilities are potentially preventable. Our hospital is the only level 1 pediatric trauma center (PTC) in our state, and we are developing a pediatric trauma telehealth network to help keep certain injured children closer to home. We instituted a pediatric trauma telehealth program with a partnering community-based hospital in our state and aim to report our experience over the first year. All pediatric trauma patients that presented to our partnering hospital from January 2019 to February 2020 were reviewed. Disposition was: a) telehealth consultation, b) admission to the children's unit without a telehealth consultation per our head trauma protocol, or c) transfer without telehealth consultation. Data on demographics, hospital course, and disposition were collected via chart review. Eight patients underwent telehealth consults and another 8 patients were admitted to the partnering hospital's children's unit based on the head trauma protocol without a telehealth consult. Patient's ages ranged from 7 months to 15 years. Of the patients that underwent telehealth consult, 7 presented with a head injury and 1 presented with a rib fracture/small pneumothorax. The patient with a pneumothorax was observed for 6 h and discharged home after a repeat chest x-ray was stable. All 15 patients with head injuries were observed and discharged from either the emergency department or children's unit after passing concussion testing. No patients required transfer to our PTC after observation, and none were readmitted. Fifty-six patients were transferred without telehealth consultation, and 3 of these patients could potentially have avoided transfer with a telehealth consultation. Telehealth in pediatric trauma can be a safe mechanism for preventing the transfer of patients that can be safely observed at a partnering hospital. From a facility that transfers an average of 30 trauma patients per year to our hospital, this program prevented 16 such transfers. Development of a head trauma protocol in collaboration with a pediatric neurosurgeon leads to an unexpected number of patients being admitted to the partnering hospital for observation without utilization of a telehealth consultation. Retrospective study. III.


Selection of large and objectively measurable target lesions in EORTC phase II trials: impact on recruitment and response rate. EORTC Soft Tissue and Bone Sarcoma Group (STBSG).
The EORTC has recently issued minimum requirements for target lesions in phase II trials, aiming at a decrease in measurement errors [minimum size, computer tomography (CT) scan or ultrasound for deep lesions]. Their impact on recruitment and response has been retrospectively studied in a trial of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), investigating high-dose chemotherapy in patients with advanced soft tissue sarcoma, where 46/103 objective responses were seen, including 10 complete responses. For the 20 patients who did not satisfy the criteria, a similar objective response rate and a significantly higher complete response rate were reported. Among 265 target lesions, the same trends were observed when comparing small to large lesions, for different tumour sites. For deep lesions clinically assessed, significantly higher response rates were reported than for those measured by CT scans or ultrasound. The new stricter EORTC criteria improve the reliability of measurements and have been adopted for future phase II trials of the STBSG. This will not result in the selection of potentially poor responders. Less than 20% of the present recruitment will be lost.


Complete chromogen separation and analysis in double immunohistochemical stains using Photoshop-based image analysis.
Simultaneous detection of two different antigens on paraffin-embedded and frozen tissues can be accomplished by double immunohistochemistry. However, many double chromogen systems suffer from signal overlap, precluding definite signal quantification. To separate and quantitatively analyze the different chromogens, we imported images into a Macintosh computer using a CCD camera attached to a diagnostic microscope and used Photoshop software for the recognition, selection, and separation of colors. We show here that Photoshop-based image analysis allows complete separation of chromogens not only on the basis of their RGB spectral characteristics, but also on the basis of information concerning saturation, hue, and luminosity intrinsic to the digitized images. We demonstrate that Photoshop-based image analysis provides superior results compared to color separation using bandpass filters. Quantification of the individual chromogens is then provided by Photoshop using the Histogram command, which supplies information on the luminosity (corresponding to gray levels of black-and-white images) and on the number of pixels as a measure of spatial distribution. (J Histochem Cytochem 47:119-125, 1999)


Three-dimensional inhomogeneity of zeolite structure and composition revealed by electron ptychography.
Structural and compositional inhomogeneity is common in zeolites and considerably affects their properties. Thickness-limited lateral resolution, lack of depth resolution, and electron dose-constrained focusing limit local structural studies of zeolites in conventional transmission electron microscopy (TEM). We demonstrate that a multislice ptychography method based on four-dimensional scanning TEM (4D-STEM) data can overcome these limitations. Images obtained from a ~40-nanometer-thick MFI zeolite exhibited a lateral resolution of ~0.85 angstrom that enabled the identification of individual framework oxygen (O) atoms and the precise determination of the orientations of adsorbed molecules. Furthermore, a depth resolution of ~6.6 nanometers allowed probing of the three-dimensional distribution of O vacancies, as well as the phase boundaries in intergrown MFI and MEL zeolites. The 4D-STEM ptychography can be generally applied to other materials with similar high electron-beam sensitivity.


[The phylogenetic position of Chlamydia strains isolated from monkeys and humans with Chlamydial pathology in the family Chiamydiaceae. Genotypic and phenotypic properties of this pathogen].
Based on the results of the comparative analysis concerning relatedness and evolutional difference of the 16S - 23S nucleotide sequences of the middle ribosomal cluster and 23S rRNA I domain, and based on identification of phylogenetic position for Chlamydophila pneumoniae and Chlamydia trichomatis strains released from monkeys, relatedness of the above stated isolates with similar strains released from humans and with strains having nucleotide sequences presented in the GenBank electronic database has been detected for the first time ever. Position of these isolates in the Chlamydiaceae family phylogenetic tree has been identified. The evolutional position of the investigated original Chlamydia and Chlamydophila strains close to analogous strains from the GenBank electronic database has been demonstrated. Differences in the 16S - 23S nucleotide sequence of the middle ribosomal cluster and 23S rRNA I domain of plasmid and non-plasmid Chlamydia trachomatis strains released from humans and monkeys relative to different genotype groups (group B- B, Ba, D, Da, E, L1, L2, L2a; intermediate group - F, G, Ga) have been revealed for the first time ever. Abnormality in incA chromosomal gene expression resulting in Chlamydia life and development cycle disorder and decrease of Chlamydia virulence can be related to probable changes in the nucleotide sequence of the gene under consideration.


The contribution of magnetic resonance imaging to the evaluation of intracardiac tumors diagnosed by echocardiography.
MAgnetic resonance (MR) imaging was performed in 14 patients with intracavitary cardiac tumors diagnosed by echocardiography. Except in the patients whose echocardiograms were diagnostic of atrial myxomas, this modality contributed important additional anatomic information regarding the tumor's relationship to the normal intracardiac structures and/or its extension to the adjacent vascular and mediastinal structures. The MR findings correlated extremely well with the findings in all 12 patients who underwent surgical exploration or postmortem examination, and in the other two patients, MR guided the decision to obtain transvenous biopsy samples of their right heart masses.


Evaluation of sealants to mitigate the release of per- and polyfluoroalkyl substances (PFAS) from AFFF-impacted concrete: Characterization and forecasting.
Per- and polyfluoroalkyl substances (PFAS) within concrete pads impacted by historical firefighting training using aqueous film-forming foam (AFFF) may be potential secondary sources of PFAS due to surficial leaching. This study aimed to (i) characterize the effectiveness of two commercially available sealants (Product A and Product B) in mitigating leaching of five PFAS (e.g., PFOS, PFOA, PFHxS, PFHxA, 6:2 FTS) from concrete surfaces at the laboratory-scale, and (ii) develop a model to forecast cumulative leaching of the same five PFAS over 20 years from sealed and unsealed concrete surfaces. Laboratory trials demonstrated that both sealants reduced the surficial leaching of the five PFAS studied, and Product B demonstrated a comparatively greater reduction in surface leaching than Product A as measured against unsealed controls. The cumulative PFOS leaching from an unsealed concrete surface is estimated by the model to be about 400 mg/m2 over 20 years and reached asymptotic conditions after 15 years. In contrast, the model output suggests asymptotic conditions were not achieved within the modeled time of 20 years after sealing with Product A and 85% of PFOS was predicted to have leached (∼340 mg/m2). Negligible leaching of PFOS after sealing with Product B was observed ( < 5 × 10-9 mg/m2). Results from modeled rainfall scenarios suggest PFAS leachability is reduced from sealed versus unsealed AFFF-impacted concrete surfaces.


Molecular mechanisms involved in the protective actions of Selective Estrogen Receptor Modulators in brain cells.
Synthetic selective modulators of the estrogen receptors (SERMs) have shown to protect neurons and glial cells against toxic insults. Among the most relevant beneficial effects attributed to these compounds are the regulation of inflammation, attenuation of astrogliosis and microglial activation, prevention of excitotoxicity and as a consequence the reduction of neuronal cell death. Under pathological conditions, the mechanism of action of the SERMs involves the activation of estrogen receptors (ERs) and G protein-coupled receptor for estrogens (GRP30). These receptors trigger neuroprotective responses such as increasing the expression of antioxidants and the activation of kinase-mediated survival signaling pathways. Despite the advances in the knowledge of the pathways activated by the SERMs, their mechanism of action is still not entirely clear, and there are several controversies. In this review, we focused on the molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a response to treatment with raloxifene and tamoxifen.


FMRFamide inhibition of a molluscan heart is accompanied by increases in cyclic AMP.
The molluscan neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2) inhibits the beat of isolated ventricles of the freshwater clam Lampsilis claibornensis. The decline in frequency and diastolic tone precedes the dose- and time-dependent increase in cAMP also produced by the peptide. Phosphodiesterase inhibitors (theophylline, 3-isobutyl-1-methylxanthine) and cAMP analogs also inhibit Lampsilis hearts, but only at high doses (10(-5)-10(-3)M). Again, the inhibition by theophylline is accompanied by a rise in cAMP. Nevertheless, the delayed increase in cAMP levels following FMRFamide treatment may suggest that cAMP is not mediating the onset of FMRFamide cardioinhibition.


A lightweight network guided with differential matched filtering for retinal vessel segmentation.
The geometric morphology of retinal vessels reflects the state of cardiovascular health, and fundus images are important reference materials for ophthalmologists. Great progress has been made in automated vessel segmentation, but few studies have focused on thin vessel breakage and false-positives in areas with lesions or low contrast. In this work, we propose a new network, differential matched filtering guided attention UNet (DMF-AU), to address these issues, incorporating a differential matched filtering layer, feature anisotropic attention, and a multiscale consistency constrained backbone to perform thin vessel segmentation. The differential matched filtering is used for the early identification of locally linear vessels, and the resulting rough vessel map guides the backbone to learn vascular details. Feature anisotropic attention reinforces the vessel features of spatial linearity at each stage of the model. Multiscale constraints reduce the loss of vessel information while pooling within large receptive fields. In tests on multiple classical datasets, the proposed model performed well compared with other algorithms on several specially designed criteria for vessel segmentation. DMF-AU is a high-performance, lightweight vessel segmentation model. The source code is at https://github.com/tyb311/DMF-AU.


Population-based study of serum hepatitis B virus DNA in Gabon.
The prevalence of serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) was measured in a Gabonese community at high risk for HBV infection. Among 698 subjects 5 to 24 years old, the prevalence of HBsAg was 11.1% vs. 57.9% for anti-HBs and 7.2% for anti-HBc alone. The prevalence of HBeAg among HBsAg-positive subjects was 26.5% vs. 59.5% for anti-HBe. The prevalence of HBV DNA tested by a hybridization spot test was 2.1% in the overall population and 18.7% among HBsAg-positive subjects. HBV DNA was found in 15 of 21 HBeAg-positive subjects but in none of the subjects positive for anti-HBe or negative for both HBeAg and anti-HBe. HBV DNA was not detected in any HBsAg negative subjects. The prevalence of HBV DNA decreased with age. This low prevalence of HBV DNA contrasts with the high level of endemicity in the study population.


Maximal and Explosive Muscle Strength During Hip Adduction Squeeze and Hip Abduction Press Test Using A Handheld Dynamometer: An Intra- and Inter-tester Reliability Study.
Hip adduction and abduction muscle function plays an important role for risk of groin pain in athletes. Maximal isometric strength can be obtained clinically using a handheld dynamometer. However, in very strong athletes this is challenging, as external fixation of the dynamometer is needed for reliable measures. An alternative to unilateral testing, is the long-lever hip adduction squeeze test and a novel bilateral hip abduction press test. While promising intra-tester reliability has been found for maximal strength during the long-lever hip adduction squeeze test, inter-tester reliability may be more challenging during both maximal and explosive strength measurements. The aim of the present study was to assess intra- and inter-tester reliability of maximal, and explosive strength during the long lever hip adduction squeeze test and the long lever hip abduction press test in healthy adults using a hand-held dynamometer. Intra- and interrater reliability study. Forty-nine healthy subjects were included for intra- (n=20) and inter-tester reliability (n=29). Subjects performed the hip adduction long lever squeeze test and the bilateral hip abduction press test in a randomized order. Maximal isometric strength and early (0-100 ms) and late (0-200 ms) phase rate of force development (explosive muscle strength) was obtained using a hand-held dynamometer. Relative reliability for all tests was assessed using ICC2,1 two-way mixed model with absolute agreement, thereby taking bias between testers into account. Maximal isometric strength showed good intra- and inter-tester reliability for adduction (ICC: 0.93-0.97) and abduction (ICC: 0.88-0.92). For 0-200 ms rate of force development, both the squeeze and press test showed good intra-tester reliability (ICC: 0.85-0.87), whereas inter-tester reliability was good for hip adduction squeeze (ICC: 0.75) and moderate for hip abduction press (ICC: 0.71). For 0-100 ms rate of force development, the hip abduction press test showed good intra-tester reliability (ICC: 0.78). Remaining tests for intra- and inter-tester reliability showed moderate reliability (ICC: 0.50-0.71). Assessment of maximal isometric strength in hip adduction squeeze and abduction press test showed good intra- and inter-tester reliability, whereas only 0-200 ms rate of force development demonstrated good intra-tester reliability of both tests. Therefore, rate of force development should preferably be conducted by the same tester, while the long lever squeeze and press test can reliably be used within- and between testers to measure maximal isometric strength. 3©The Author(s).


cAMP activates transcription of the human glucocorticoid receptor gene promoter.
Glucocorticoids and cAMP regulate, either in a synergistic or additive fashion, the transcription of multiple genes, although some antagonistic effects of dexamethasone on cAMP-activated transcription have been described. The increased glucocorticoid receptor (GR) mediated response of some cell types, as a result of augmented cAMP, has been considered to be mainly due to an increased stability of GR mRNA, although other plausible explanations should not be ruled out. We studied the possibility that GR transcription itself could be affected by cAMP levels. HeLa cells were transfected with human GR (hGR) promoter constructs and their transcriptional activity determined after inducing a cAMP increase with forskolin. We found that forskolin almost doubled the transcriptional activity of the promoter construct spanning -2995 to +38 of the hGR, whereas no significant variations were observed with shorter chimeras containing sequences downstream -979. Shift mobility showed binding of CREB in vitro to a putative cAMP responsive element located at -1000, suggesting that hGR may be upregulated by cAMP at the transcriptional level, thus adding a new mechanism ascribable to this second messenger, which in conjunction with the cAMP-induced GR mRNA increased stability, would lead to a more precise control of the amount of GR protein within the cell.


Complex meristematic activity induced by Eucecidoses minutanus on Schinus engleri turns shoots into galls.
Gall-inducing organisms change the development of their host plant organs, resulting in ontogenetic patterns not observed in the non-galled plants. Distinct taxa induce galls on Schinus spp., manipulating meristematic patterns in the host plant in distinct ways. Here we report ontogenetic novelties induced in the lateral buds of S. engleri by Eucecidoses minutanus, a Cecidosidae, whose galls have been poorly understood. The anatomy, histochemistry, and histometry of galls in distinct phases of development, non-galled buds, and stems of Schinus engleri were analyzed in parallel with the instars of E. minutanus to detail the morphogenetic changes in the host with each larval stage. Ontogenetic phases of the galls were intricately associated with larval development. First and second-instar larvae induced pericycle and pith cells to dedifferentiate into the gall inner meristem, where hyperplasia and cell hypertrophy characterized the growth and development phase of the gall. The innermost layers were lipid-rich nutritive cells that lined the larval chamber. Additional vascular bundle rows were produced in young galls. Third and fourth instar-larvae were associated with the gall maturation phase: centripetal lignification of the outer parenchyma cell layers, epidermal stratification, and activation of a cambium-like meristem (CLM). The CLM activity resulted in new layers of nutritive cells that differentiated inward as the first layers of nutritive cells were consumed by E. minutanus larvae, and, also, in more parenchyma cell layers that formed outward. All tissues between the innermost layer of nutritive tissue that surround the gall chamber and the outermost layer of the dermal system that externally covers the gall form the gall wall, and increased in thickness until the end of gall maturation. E. minutanus induces a structurally complex globoid stem gall, modifying all host plant tissues and stimulating a novel meristematic pattern in S. engleri. The gall developmental stages are each related to specific gall-inducing instars, as gall development progresses according to the development of E. minutanus.


Effects of exercise intervention on event-related potential and task performance indices of attention networks in children with developmental coordination disorder.
The study investigated whether 10-week soccer training can benefit the inhibitory control and neuroelectric indices in children with developmental coordination disorder (DCD). Fifty-one children were divided into groups of typically developing (TD, n=21), DCD-training (n=16), and DCD non-training (n=14) individuals using the for Children test, and, before and after training, were assessed with the visuospatial attention orienting task with their lower extremities, while brain event-related potentials (ERPs) were concurrently recorded. The results indicated that, when compared to TD children, children with DCD responded significantly more slowly across conditions of the visuospatial attention orienting task and showed a deficit of inhibitory control capacity in their lower extremities, whereas no group differences were observed for the accuracy rate. Neuroelectric data indicated that, before training, P3 amplitude was smaller and P3 latency was slower for both DCD groups compared to TD children across conditions of the visuospatial attention orienting task; after training, the beneficial effects were seen in the strength of inhibitory control and P3 latency in the DCD-training group. The data suggest that soccer training resulted in significant improvements in ERP and task performance indices for the children with DCD.


Effective Implementation and Utilization of Checklists in Surgical Patient Safety.
The success of patient safety and quality improvement interventions depends, in part, on the effectiveness of implementation. Surgical safety checklists have been introduced into thousands of operating rooms across 6 continents since the debut of the original World Health Organization 19-item checklist in 2008. However, the effect of checklists on patient outcomes has varied. Here, we review 5 examples of large-scale efforts (eg, population level or across health systems) where surgical checklists were introduced into the operating room and the associated effects on patient outcomes. Each experience provides an opportunity to reflect on best practices that inform strategies for effective implementation.


Percutaneous coronary stenting in guide-induced aortocoronary dissection: angiographic and CT findings.
We report here on a case of accidental aortocoronary dissection that occurred during the engagement of a guiding catheter. This resulted in an antegrade dissection into the right coronary artery, and a retrograde extension of the dissection into the Sinus of Valsalva and the ascending aorta up to the aortic arch. It was successfully treated with a stent deployment at the RCA ostium; this restored optimal coronary blood flow and there was a complete resolution of the aortic dissection as was documented by coronary angiography and the follow-up CT scan.


Expansion rate of nonaneurysmatic abdominal aorta: over 10 years of follow-up CT studies.
Expansion rate of the nonaneurysmatic abdominal aorta (NAA) is completely unknown. The purpose was to evaluate the expansion rate of the NAA and the factors influencing its enlargement. 114 subjects without aortic disease were entered into this retrospective study (mean age: 58.7 years). In all subjects, follow-up CT studies were obtained for more than 10 years after initial CT studies (mean: 147.0 months). The diameter of the abdominal aorta was measured at two sites (suprarenal and infrarenal abdominal aorta), and the growth rate was calculated at each site. The growth rate of NAA and the factors influencing its enlargement were evaluated. In 68 (59.6%), the suprarenal segment of NAA increased in size with a mean growth rate of 1.3mm/10 years. In 49 subjects (43.0%), the infrarenal segment of NAA increased in size during the follow-up period with the mean growth rate of 1.0mm/10 years. The mean growth rate was significantly higher in the suprarenal segment (p=0.002). The suprarenal segment of NAA and presence of hyperlipidemia were significant risk factors for NAA enlargement. NAA enlargement is more likely to occur in the suprarenal segment than in the infrarenal segment. The presence of hyperlipidemia was also a significant risk factor for NAA enlargement.


The inhibitory effect of curcumin via fascin suppression through JAK/STAT3 pathway on metastasis and recurrence of ovary cancer cells.
Fascin is an actin-binding protein and highly expressed in ovarian cancer cells. It is associated with metastasis of cancer and may be a useful prognostic factor. Anticancer activity of curcumin is related to its effect on several signaling mechanisms. Although there have been many reports regarding the anticancer properties of curcumin, its inhibitory effects on migration and invasion of ovarian cancer cells, particularly in the context of fascin expression, have not been reported. The purpose of this study was to investigate the effect of curcumin on fascin expression in ovarian cancer cells and to propose a possible mechanism for the anticancer activity of curcumin through reduced fascin expression. SKOV3, human epithelial ovary cancer cell line, was cultured with curcumin at various dose and duration. The fascin was quantified using cell viability test and Western blot. To determine the effect of curcumin on the upstream pathway of fascin expression, the signal transducer and activator of transcription 3 (STAT3) was analyzed by sandwich-ELISA. Attachment assay, migration assay and invasion assay were analyzed to approve the change of cellular invasiveness of ovary cancer after curcumin. To determine the morphological changes of ovarian cancer cells by curcumin, immunofluorescence was performed. MTS assays showed that cell viability was different at various concentration of curcumin, and as concentration increased, cell viability tended to decrease. Curcumin appears to suppress fascin expression, even with a minimal concentration and short exposure time. Also, curcumin may suppress fascin expression in ovarian cancer cells through STAT3 downregulation. The attachment assay, migration assay and invasion assay of the ovarian cancer cells exhibited a statistically significant decrease. Immunofluorescence revealed a change of cell shape from a typical form of uninfluenced cells to a more polygonal appearance, with a significant reduction in filopodia formation. Curcumin reduces fascin expression through JAK/STAT3 pathway inhibition, which interferes with the cellular interactions essential for the metastasis and recurrence of ovarian cancer cells. Higher curcumin concentrations and longer exposure times concomitantly decreased fascin expression.


Confidentiality protections versus collaborative care in the treatment of substance use disorders.
Practitioners in federally-assisted substance use disorder (SUD) treatment programs are faced with increasingly complex decisions when addressing patient confidentiality issues. Recent policy changes, intended to make treatment more available and accessible, are having an impact on delivery of SUD treatment in the United States. The addition of electronic health records provides opportunity for more rapid and comprehensive communication between patients' primary and SUD care providers while promoting a collaborative care environment. This shift toward collaborative care is complicated by the special protections that SUD documentation receives in SUD treatment programs, which vary depending on what care is provided and the setting where the patient is treated. This article explores the special protections for substance abuse documentation, discrepancies in treatment documentation, ways to deal with these issues in clinical practice, and the need for more knowledge about how to harmonize treatment in the SUD and primary care systems.


Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker.
This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients. Sixty HER2-positive MBC patients were enrolled in the present study. Before the initiation of systemic treatment, CTCs from 7.5 ml of blood were analyzed using the CellSearch system. The progression-free survival (PFS) of the patients was estimated using Kaplan-Meier survival curves. CTCs were detected in 45% (27/60) of the patients, who had shorter median PFS than those without CTCs (2.5 vs. 7.5 months, P=0.0125). Furthermore, referring to the standard HER2 testing that uses immunohistochemistry (IHC), we proposed a CTC HER2-positive criterion, defined as >30% of CTCs over-expressing HER2. Among patients undergoing anti-HER2 therapy, those with HER2-positive CTCs had longer PFS (8.8 vs. 2.5 months, P=0.002). Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P=0.001). Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P=0.499). Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients. To test this idea, additional large cohort, multi-center and prospective clinical trials are needed.


Occlusion cues contribute to orientation judgments of occlusion-defined contours.
Occlusion cues defining a contour in a 2-D stimulus pattern were shown to contribute to the accuracy of orientation judgments of that contour. The stimulus pattern was altered so that the occlusion cues became ambiguous, by introducing a textured background suggesting transparency of the stimulus pattern. Orientation judgments then became significantly less accurate. This finding shows that occlusion cues in 2-D patterns can be behaviorally relevant, in addition to generating the subjective percept commonly known as an illusory contour. The disruptive effect of the textured background on orientation judgments remained when no texture elements were present in the vicinity of the contour. This suggests that the generation of occlusion-defined contours relies as much on an evaluation of the surfaces at either side of the contour as being opaque as it does on local encoding of occlusion cues close to the contour. Finally, orientation sensitivity measured with contours defined by other than occlusion cues was not altered after the introduction of a textured background.


Extrinsic intestinal denervation modulates tumor development in the small intestine of Apc(Min/+) mice.
Innervation interacts with enteric immune responses. Chronic intestinal inflammation is associated with increased risk of colorectal cancer. We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model. Experiments were performed with male Apc(Min/+) or wild type mice (4 weeks old, body weight approximately 20 g). Subgroups with subdiaphragmatic vagotomy (apcV/wtV), sympathetic denervation of the small intestine (apcS/wtS) or sham operated controls (apcC/wtC) were investigated (n = 6-14 per group). Three months after surgical manipulation, 10 cm of terminal ileum were excised, fixed for 48 h in 4% paraformaldehyde and all tumors were counted and their area determined in mm(2) (mean ± standard error of the mean (SEM)). Whole mounts of the muscularis of terminal ileum and duodenum (internal positive control) were also stained for tyrosine hydroxylase to confirm successful sympathetic denervation. Tumor count in Apc(Min/+) mice was 62 ± 8 (apcC), 46 ± 11 (apcV) and 54 ± 8 (apcS) which was increased compared to wildtype controls with 4 ± 0.5 (wtC), 5 ± 0.5 (wtV) and 5 ± 0.6 (wtS; all p < 0.05). For Apc(Min/+) groups, vagotomized animals showed a trend towards decreased tumor counts compared to sham operated Apc(Min/+) controls while sympathetic denervation was similar to sham Apc(Min/+). Area covered by tumors in Apc(Min/+) mice was 55 ± 10 (apcC), 31 ± 8 (apcV) and 42 ± 8 (apcS) mm(2), which was generally increased compared to wildtype controls with 7 ± 0.6 (wtC), 7 ± 0.4 (wtV) and 7 ± 0.6 (wtS) mm(2) (all p < 0.05). In Apc(Min/+) groups, tumor area was decreased in vagotomized animals compared to sham operated controls (p < 0.05) while sympathetically denervated mice showed a minor trend to decreased tumor area compared to controls. Extrinsic innervation of the small bowel is likely to modulate tumor development in Apc(Min/+) mice. Interrupted vagal innervation, but not sympathetic denervation, seems to inhibit tumor growth.


Bifunctional Au@Pt/Au nanoparticles as electrochemiluminescence signaling probes for SARS-CoV-2 detection.
A novel immunosensor based on electrochemiluminescence resonance energy transfer (ECL-RET) for the sensitive determination of N protein of the SARS-CoV-2 coronavirus is described. For this purpose, bifunctional core@shell nanoparticles composed of a Pt-coated Au core and finally decorated with small Au inlays (Au@Pt/Au NPs) have been synthesized to act as ECL acceptor, using [Ru (bpy)3]2+ as ECL donor. These nanoparticles are efficient signaling probes in the immunosensor developed. The proposed ECL-RET immunosensor has a wide linear response to the concentration of N protein of the SARS-CoV-2 coronavirus with a detection limit of 1.27 pg/mL. Moreover, it has a high stability and shows no response to other proteins related to different virus. The immunosensor has achieved the quantification of N protein of the SARS-CoV-2 coronavirus in saliva samples. Results are consistent with those provided by a commercial colorimetric ELISA kit. Therefore, the developed immunosensor provides a feasible and reliable tool for early and effective detection of the virus to protect the population.


Molecular study of the diffusional process of DMSO in double lipid bilayers.
As a way to quantify the diffusion process of molecular compounds through biological membranes, we investigated in this study the dynamics of DMSO through an 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) bilayer system. To properly account for the diffusion of DMSO due to a concentration gradient, a double DPPC bilayer was setup for our simulations. In such configuration, the aqueous phases can be explicitly associated with the extra and intracellular domains of the membrane, which is seldom the case in studies of single lipid bilayer due to the periodicity imposed by the simulations. DMSO molecules were initially contained in one of the aqueous phases (extracellular region) at a concentration of 5 wt.%. Molecular dynamics simulation was performed in this system for 95 ns at 350 K and 1 bar. The simulations showed that although many DMSO molecules penetrated the lipid bilayer, only about 10% of them crossed the bilayer to reach the other aqueous phase corresponding to the intracellular region of the membrane. The simulation time considered was insufficient to reach equilibrium of the DMSO concentration between the aqueous phases. However, the simulations provided sufficient information to estimate parameters to apply Fick's Law to model the diffusion process of the system. Using this model, we predicted that for the time considered in our simulation, the concentration of DMSO in the intracellular domain should have been about half of the actual value obtained. The model also predicted that equilibrium of the DMSO concentration in the system would be reached after about 2000 ns, approximately 20 times longer than the performed simulation.


Elasticity of Ferropericlase across the Spin Crossover in the Earth's Lower Mantle.
Knowing the elasticity of ferropericlase across the spin transition can help explain seismic and mineralogical models of the lower-mantle including the origin of seismic heterogeneities in the middle to lowermost parts of the lower mantle. However, the effects of spin transition on full elastic constants of ferropericlase remain experimentally controversial due to technical challenges in directly measuring sound velocities under lower-mantle conditions. Here we have reliably measured both VP and VS of a single-crystal ferropericlase ((Mg0.92,Fe0.08)O) using complementary Brillouin Light Scattering and Impulsive Stimulated Light Scattering coupled with a diamond anvil cell up to 96 GPa. The derived elastic constants show drastically softened C11 and C12 within the spin transition at 40-60 GPa while C44 is not affected. The spin transition is associated with a significant reduction of the aggregate VP/VS via the aggregate VP softening because VS softening does not visibly occur within the transition. Based on thermoelastic modelling along an expected geotherm, the spin crossover in ferropericlase can contribute to 2% reduction in VP/VS in a pyrolite mineralogical model in mid lower-mantle. Our results imply that the middle to lowermost parts of the lower-mantle would exhibit enhanced seismic heterogeneities due to the occurrence of the mixed-spin and low-spin ferropericlase.


Incidence and risk factors of recurrence after surgery for pathology-proven diverticular disease.
Diverticular disease is a common problem in Western countries. Rationale for elective surgery is to prevent recurrent complicated diverticulitis and to reduce emergency procedures. Recurrent diverticulitis occurs in about 10% after resection. The pathogenesis for recurrence is not completely understood. We studied the incidence and risk factors for recurrence and the overall morbidity and mortality of surgical therapy for diverticular disease. Medical records of 183 consecutive patients with pathology-proven diverticulitis were eligible for evaluation. Mean duration of follow-up was 7.2 years. Number of preoperative episodes, emergency or elective surgeries, type of operation, level of anastomosis, postoperative complications, persistent postoperative pain, complications associated with colostomy reversal, and recurrent diverticulitis were noted. The Kaplan-Meier method was used to calculate the cumulative probability of recurrence. Cox regression was used to identify possible risk factors for recurrence. The incidence of recurrence was 8.7%, with an estimated risk of recurrence over a 15-year period of 16%. Risk factors associated with recurrence were (younger) age (p < 0.02) and the persistence of postoperative pain (p < 0.005). Persistent abdominal pain after surgery was present in 22%. Eighty percent of patients who needed emergency surgery for acute diverticulitis had no manifestation of diverticular disease prior to surgery. In addition, recurrent diverticulitis was not associated with a higher percentage of emergency procedures. Estimated risk of recurrence is high and abdominal complaints after surgical therapy for diverticulitis are frequent. Younger age and persistence of postoperative symptoms predict recurrent diverticulitis after resection. The clinical implication of these findings needs further investigation. The results of this study support the careful selection of patients for surgery for diverticulitis.


TET-Yeasate: An engineered yeast whole-cell lysate-based approach for high performance tetracycline degradation.
The widespread of tetracycline (TC) residues in anthropogenic and natural environments pose an immediate threat to public health. Herein, we established the TET-Yeasate, an approach based on whole-cell lysate of engineered yeast, to mitigate the TC contamination in environment. The TET-Yeasate is defined as the biological matrix of whole cell lysate from engineered yeast that containing TC-degradative components (Tet(X), NADPH, Mg2+) and protective macromolecules. The TET-Yeasate was able to efficiently eliminate TC residues in tap water (98.8%), lake water (77.6%), livestock sewage (87.3%) and pharmaceutical wastewater (35.3%) without necessity for exogenous addition of expensive cofactors. The TET-Yeasate was further developed into lyophilized form for ease of storage and delivery. The TET-Yeasate in lyophilized form efficiently removed up to 74.6% TC residue within 0.25 h. In addition, the lyophilization confers promising resilience to TET-Yeasate against adverse temperatures and pH by maintaining degradation efficacy of 85.69%-97.83%. The stability test demonstrated that the biomacromolecules in lysate served as natural protectants that exerted extensive protection on TET-Yeasate during the 14-day storage at various conditions. In addition, 5 potential degradation pathways were elaborated based on the intermediate products. Finally, the analysis indicated that TET-Yeasate enjoyed desirable bio- and eco-safety without introduction of hazardous intermediates and spread of resistance genes. To summary, the TET-Yeasate based on whole cell lysate of engineered yeast provides a cost-effective and safe alternative to efficiently remove TC residues in environment, highlighting the great potential of such whole-cell based methods in environmental decontamination.


Chronic HIV encephalitis--II. Clinical aspects.
Combined medical, neurological, and serological investigations were carried out in 59 patients infected with human immunodeficiency virus (HIV). In stage I clinical and neuropsychiatric testing did not reveal evidence for HIV encephalitis as diagnosed by local antibody production in CSF. Neuropsychiatric abnormalities, brain atrophy, memory and cognitive impairment reliably indicated HIV encephalitis in later stages. The commonest symptoms were cerebellar and brainstem signs, followed by dementia. Epileptic fits and hemiparesis always were associated with cerebral toxoplasmosis. A polyneuropathy was frequently found but other causes have to be considered.