An EGF receptor-targeting amphinase recombinant protein mediates anti-tumor activity in vitro and in vivo.
Utilizing cytotoxic proteins linked to tumor targeting molecules as anti-tumor drugs is a promising approach. However, most cytotoxins derived from bacteria or plants have inherent problems such as large molecular weights and they trigger a strong immune system reaction, which leads to drug failure and serious side effects. Amphinase (Amph) is a ribonuclease with a low molecular weight that is found in northern leopard frog oocytes. It has strong cytotoxicity against tumor cell lines in vitro and weak immunogenicity in vivo, and is a promising candidate in the development of targeted drugs. Transforming growth factor-α (TGF-α) that binds to the epidermal growth factor receptor (EGFR) is being used as a targeting molecule for the treatment of EGFR high-expressing tumors. In this study, we expressed and purified a recombinant amphinase and its TGF-α fusion protein (AGT) separately from Escherichia coli. AGT exhibited more significant cytotoxicity in vitro on EGFR high-expressing tumor cell lines, and stronger anti-tumor effects in vivo. This fusion protein also exhibited unusual thermostability, low in vivo immunogenicity, and side effects. Our results provide a new entry point for the development of novel, highly efficient anti-tumor targeting biological agents with low immunogenicity.


Platinum-based chemotherapy for variant castrate-resistant prostate cancer.
Clinical features characteristic of small-cell prostate carcinoma (SCPC), "anaplastic," often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined "anaplastic" clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low prostate-specific antigen levels relative to tumor burden, or short response to androgen deprivation therapy. A 120-patient phase II trial of first-line carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after four cycles of CD and EP, respectively. Median overall survival (OS) was 16 months [95% confidence interval (CI), 13.6-19.0 months]. Of the seven "anaplastic" criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Our findings support the hypothesis that patients with "anaplastic" prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with castration-resistant prostate cancer and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population.


Characterization and functional analysis of a recombinant tau class glutathione transferase GmGSTU2-2 from Glycine max.
The plant tau class glutathione transferases (GSTs) perform diverse catalytic as well as non-catalytic roles in detoxification of xenobiotics, prevention of oxidative damage and endogenous metabolism. In the present work, the tau class isoenzyme GSTU2-2 from Glycine max (GmGSTU2-2) was characterized. Gene expression analysis of GmGSTU2 suggested a highly specific and selective induction pattern to osmotic stresses, indicating that gene expression is controlled by a specific mechanism. Purified, recombinant GmGSTU2-2 was shown to exhibit wide-range specificity towards xenobiotic compounds and ligand-binding properties, suggesting that the isoenzyme could provide catalytic flexibility in numerous metabolic conditions. Homology modeling and phylogenetic analysis suggested that the catalytic and ligand binding sites of GmGSTU2-2 are well conserved compared to other tau class GSTs. Structural analysis identified key amino acid residues in the hydrophobic binding site and provided insights into the substrate specificity of this enzyme. The results established that GmGSTU2-2 participates in a broad network of catalytic and regulatory functions involved in the plant stress response.


Preventing catastrophic injury and death in collegiate athletes: interassociation recommendations endorsed by 13 medical and sports medicine organisations.
The following organisations endorsed this document: American Association of Neurological Surgeons, American Medical Society for Sports Medicine, American Orthopaedic Society for Sports Medicine, American Osteopathic Academy of Sports Medicine, College Athletic Trainers' Society, Collegiate Strength and Conditioning Coaches Association, Congress of Neurological Surgeons, Korey Stringer Institute, National Athletic Trainers' Association, National Strength and Conditioning Association, National Operating Committee for Standards on Athletic Equipment, Sports Neuropsychology Society. The following organisation has affirmed the value of this document: American Academy of Neurology. The Second Safety in College Football Summit resulted in interassociation consensus recommendations for three paramount safety issues in collegiate athletics: (1) independent medical care for collegiate athletes; (2) diagnosis and management of sport-related concussion; and (3) year-round football practice contact for collegiate athletes. This document, the fourth arising from the 2016 event, addresses the prevention of catastrophic injury, including traumatic and non-traumatic death, in collegiate athletes. The final recommendations in this document are the result of presentations and discussions on key items that occurred at the summit. After those presentations and discussions, endorsing organisation representatives agreed on 18 foundational statements that became the basis for this consensus paper that has been subsequently reviewed by relevant stakeholders and endorsing organisations. This is the final endorsed document for preventing catastrophic injury and death in collegiate athletes. This document is divided into the following components. (1) Background-this section provides an overview of catastrophic injury and death in collegiate athletes. (2) Interassociation recommendations: preventing catastrophic injury and death in collegiate athletes-this section provides the final recommendations of the medical organisations for preventing catastrophic injuries in collegiate athletes. (3) Interassociation recommendations: checklist-this section provides a checklist for each member school. The checklist statements stem from foundational statements voted on by representatives of medical organisations during the summit, and they serve as the primary vehicle for each member school to implement the prevention recommendations. (4) References-this section provides the relevant references for this document. (5) Appendices-this section lists the foundational statements, agenda, summit attendees and medical organisations that endorsed this document.


How does negative evidence impact argument strength during semantic category-based induction? An event-related potential study.
Negative evidence may influence category-based inductive reasoning, but the underlying time course of cognitive brain processing is unclear. This study adopted event-related potentials (ERPs) to investigate this effect by manipulating the category type (related vs. unrelated) and argument type (positive vs. negative) in a semantic category-based induction task. The behavioral results showed that, under unrelated conditions, a negative argument produced greater argument strength and shorter reaction time than a positive argument did. Meanwhile, the ERP results found a negative argument elicited larger P300, N400, and slow negative component amplitudes than a positive argument, which could possibly embody the expectation-related processing produced by memory updating, semantic integration, and the more complex inference-driven information integration and interpretation processes and cognitive load in hypothesis generation. This study provides novel evidence on the temporal course of how negative evidence influences argument strength during semantic category-based induction.


The role of balloon pulmonary angioplasty and pulmonary endarterectomy: Is chronic thromboembolic pulmonary hypertension still a life-threatening disease?
The management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched the BPA program in 2011. The aim was to analyze the survival and treatment efficacy of our CTEPH treatment program in the modern management era. We retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed from January 2011 (i.e. after the availability of BPA) to December 2019. Of forty-one patients who underwent pulmonary endarterectomy (PEA), 25 underwent additional BPA (Combination group) and the others were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group). The remaining 12 patients did not undergo any interventional treatments. The 1- and 5-year survival rates of operated patients (n = 41) were 97.4% and 90.0%, compared to 96.9% and 86.9% in not-operated patients (n = 102), respectively (p = 0.579). There was no mortality in the Combination group. Mean pulmonary artery pressure after treatments in the PEA only, Combination, and BPA only groups was 20.5 ± 6.7, 17.9 ± 4.9, and 20.7 ± 4.6 mmHg, respectively (p = 0.067, one-way ANOVA). Percent decrease of pulmonary vascular resistance in each treatment groups was -73.7 ± 11.3%, -74.3 ± 11.8%, and - 54.9 ± 22.5%, respectively (p < 0.01, one-way ANOVA). There was no significant difference in long-term survival between operated and not-operated CTEPH. Moreover, the Combination approach might have the potential to introduce notable improvements in the prognosis of CTEPH. BPA and PEA appear to be mutually complementary therapies in the modern management era.


Clinical Characteristics and Follow-Up of Seizures in Children With Anti-NMDAR Encephalitis.
Objective: To analyze the seizure characteristics of children with anti-NMDAR encephalitis. Methods: This was a retrospective analysis of 50 children with anti-NMDAR encephalitis between July 1, 2013, and July 1, 2019. Results: Fifty children with anti-NMDAR encephalitis were included in this study, of which 34 (68.0%) had seizures. During the follow-up, three patients with anti-NMDAR encephalitis secondary to herpes simplex virus encephalitis had persistent seizures. The average duration of seizures in the remaining patients was 14.6 days (range 1-47 days). Compared to patients without seizures, those with seizures were more likely to experience consciousness disturbances (p = 0.008) and epileptic form discharge on electroencephalograms (p = 0.002). The Glasgow coma scale scores (p = 0.014), and Rankin scale scores (p = 0.019) were also different. The cranial MRI findings of children were reviewed, and clinical characteristics were compared between children without cranial lesions and those with lesions in the limbic system and neocortex. Compared to children in the non-lesion group, children with lesions in the limbic system and neocortex had a higher incidence of status epilepticus. Further, children in the limbic system and neocortical lesions groups were more likely to be taking anti-seizure medications (ASMs) and receive second-line drugs. Conclusion: Long-term oral ASMs are not recommended for most children with anti-NMDAR encephalitis. Children with involvement of the limbic system and neocortex are prone to status epilepticus, and sequelae of epilepsy may remain when the neocortex is involved.


Synthesis, cytotoxicity, and antitumor activity of copper(II) and iron(II) complexes of (4)N-azabicyclo[3.2.2]nonane thiosemicarbazones derived from acyl diazines.
A series of thiosemicarbazones (TSCs) (bearing a (4)N-azabicyclo[3.2.2]nonane moiety) derived from 3-acylpyridazines, 4-acetylpyrimidines, and 2-acetylpyrazines (1-8) were synthesized as potential antitumor agents. TSCs 1-8 exhibited potent cytotoxic activity against human acute lymphoblastic leukemia CCRF-CEM cells (IC(50) = 0.05-0.77 microM) and colon adenocarcinoma HT-29 cells (IC(50) = 0.011-2.22 microM). Copper II complexes of TSCs 1-8 showed significant improvement in cytotoxic activity against HT-29 cells (IC(50) = 0.004-1.51 microM) by a factor of 3. However, complexation of ligands 1, 2, 4, and 6 with Fe(II) results in lowering of cytotoxic activity by a factor of approximately 7. In clonogenic assays involving human tumor cells of different tumor origins, compounds 5, 7, 8, and their copper complexes 5Cu(II), 7Cu(II), and 8Cu(II) exhibited remarkable cytotoxic activities with mean IC(50) values of 6, 0.18, 1, 1, 0.37, and 0.37 nM, respectively. In particular, the compounds were highly effective against human colon carcinoma and large and small cell lung carcinoma cells. The TSC derivative 5 was evaluated in vivo in nude mice bearing LXFL 529 human large cell lung carcinoma cells. With respect to antitumor activity, application of 30 mg/kg/d resulted in moderate inhibition (42%) of tumor growth. No effect on tumor growth was observed at a dose of 10 mg/kg/d. However, a dose of 40 or 60 mg/kg/d resulted in 50 and 75% death, respectively, in the treated mice, indicating the high toxicity of these compounds. Using human liver microsomes, compound 5 was found to be rapidly and highly metabolized in vitro. In actual fact, only 2% of the unmetabolized compound could be detected in the incubation medium after 5 min. The IC(50) for cell proliferation (0.006-0.022 microM) elicited by these compounds is much lower than that of the inhibition of [(14)C]cytidine incorporation into DNA (0.18-3.32 microM). These compounds are also noncell cycle specific agents. Interestingly, compounds 5, 5Cu(II), and 8 were found to be potent inducers of apoptosis in Burkitt's lymphoma cells.


Antigen-specific therapy of experimental allergic encephalomyelitis by soluble class II major histocompatibility complex-peptide complexes.
Experimental allergic encephalomyelitis is a T-cell-mediated, major histocompatibility complex (MHC) class II gene-linked autoimmune demyelinating disease of the central nervous system. To develop therapies that will specifically inactivate only the autoantigen-reactive T cells, mice were treated with soluble MHC class II molecules that had been complexed with encephalitogenic peptides. Intravenous injections of 300 micrograms of complexes consisting of encephalitogenic peptide 91-103 of myelin basic protein plus I-As protein on day 0, 4, and 7 were effective in preventing experimental allergic encephalomyelitis. Similarly, administration of 45 micrograms of I-As protein complexed to peptide 139-151 from proteolipoprotein on day 1, 4, and 7 prevented mortality and significantly reduced paralysis induced by immunization with the encephalitogenic proteolipoprotein peptide. Histological examination of sections of animal brains revealed that treatment with I-As protein plus myelin basic protein 91-103 peptide prevents the development of inflammatory lesions characteristic of experimental allergic encephalomyelitis. Thus, treatment with MHC-self-peptide complexes could serve as a highly specific therapeutic modality in treating autoimmune disease when the putative autoantigen and the MHC restricting elements are known.


The Influence of Viewing Time and Color on Architectural Aesthetic Judgment.
Understanding the factors influencing the aesthetic experience of architectures is an important topic in empirical aesthetics. In this study, we examined the effect of three architectural factors, i.e., ceiling height, openness, and contour, on viewers' aesthetic appreciation through a series of experiments. In previous studies on architectural aesthetics, participants were usually asked to view an image of an architectural space for a few seconds. The long viewing time allows them to focus on different parts of the architecture and then make an aesthetic judgment. The long viewing time, however, also makes it difficult to obtain viewers' aesthetic scores for a large number of architectural spaces in a short period. In this study, we shortened the visual presentation time to 200 ms, which allowed the viewers to have only one fixation on the image, and asked the viewers to make an aesthetic judgment. It was found that the experiment with a 200-ms viewing time could establish how the three architectural factors influenced aesthetic judgment as well as previous experiments with a 3,000-ms viewing time, suggesting that aesthetic judgment could be made within one fixation. Additionally, we investigated the impact of color on architectural aesthetic judgment by presenting grayscale images. We found that the three architectural factors influenced aesthetic judgment in similar ways for both color and grayscale images. In summary, we found that color was not a main factor modulating viewers' architectural aesthetic judgments, and we also presented a way to quickly obtain aesthetic scores for architectural spaces.


Neonatal presentation of Caroli's disease.
A neonatal presentation of Caroli's disease with severe cardiac and progressive renal pathology is described. The availability of small paediatric endoscopes ensured early diagnosis. Despite aggressive medical management, the baby died with severe bleeding complications before potentially life saving multiple organ transplantation could take place.


The way young people see the mentally ill: a questionnaire study.
The stigmatizing of the mentally ill is quite common and has numerous social and economical consequences for these individuals. The aim of this paper was to examine young peoples' beliefs regarding the mentally disordered. The authors' questionnaire regarding the interviewees' age, gender, social background and their opinions on the mentally ill was conducted among a popular portal's users. 11900 people were questioned, including 71% women. 30% of the interviewees were under the age of 19, while 34% of them were between 19 and 24 years old and 36% were over 24. 39% of the interviewees stated they closely knew at least one mentally ill person. 44% of the questioned believed a lot of criminal offenders were mentally ill. 66% of interviewees would not mind sharing a flat with a mentally disordered person, 64% would agree to work with one. Those who personally knew a mentally disordered person were more inclined to share a flat or start a relationship with such an individual, than the rest of the interviewed (51% vs. 37% for flat sharing and 38% vs. 26% for starting a relationship, p<0.001). More questioned under the age of 19 believed that significant number of criminal offenders were mentally ill, than those over the age of 24 (50% vs. 37%, p<0.001). According to the acquired data, many young Poles believe that the mentally disordered are inclined to break the law and behave aggressively. These opinions seem to be related amongst others to age and gender, and they result in unwillingness to have relations with the mentally disordered.


Donor-Acceptor Heterojunction Configurations Based on DNA-Multichromophore Arrays.
Multichromophore arrays of bis(2-thienyl)diketopyrrolopyrrole (DPP) and naphthalenediimide (NDI) with two Zn(II) -cyclens were constructed using thymidine DNA as a scaffold through the binding of the Zn(II) -cyclens with thymine bases. We demonstrate photocurrent generation in a donor-acceptor heterojunction configuration consisting of the DPP (donor) and NDI (acceptor) arrays co-immobilized on an Au electrode. The co-immobilized electrode exhibited good photocurrent responses because of the efficient charge separation between the DPP and NDI arrays. In contrast, an immobilized electrode consisting of randomly assembled DPP-NDI arrays generated no photocurrent response because DPP formed ground-state charge-transfer complexes with NDI in the randomly assembled arrays. Therefore, our approach to generate donor-acceptor heterojunctions based on DNA-multichromophore arrays is a useful method to efficiently generate photocurrent.


Prevention of biofilm colonization by Gram-negative bacteria on minocycline-rifampin-impregnated catheters sequentially coated with chlorhexidine.
Resistant Gram-negative bacteria are increasing central-line-associated bloodstream infection threats. To better combat this, chlorhexidine (CHX) was added to minocycline-rifampin (M/R) catheters. The in vitro antimicrobial activity of CHX-M/R catheters against multidrug resistant, Gram-negative Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia was tested. M/R and CHX-silver sulfadiazine (CHX/SS) catheters were used as comparators. The novel CHX-M/R catheters were significantly more effective (P < 0.0001) than CHX/SS or M/R catheters in preventing biofilm colonization and showed better antimicrobial durability.


Food safety in free-range and organic livestock systems: risk management and responsibility.
Animal production systems that offer outdoor access to the animals have become increasingly popular in the Western world due to the growing general discontent of consumers with conventional bioindustrial farming practices. These open production systems offer improved animal welfare but may create new problems for animal health, resulting in increased food safety risks from bacterial, viral, or parasitic infections or environmental contaminants. Examples of these new problems include increased Toxoplasma gondii infections in pigs and high dioxin levels in eggs from free-range hens. In this review, the relation between positive and negative points of free-range and organic livestock production systems is discussed with reference to production in The Netherlands. We investigated how proponents of more animal welfare friendly systems deal with potential negative issues in public and whether any risk communication is used. Generally, we found that the existence of a dilemma is disputed or avoided in communication with the consumer. This avoidance could be detrimental for public trust in alternative animal production systems, should problems occur. To prevent future problems, it will be necessary to communicate about the relevant types and sources of the food safety risks to the consumers. The responsibility for protecting food safety should be properly divided among the various parties involved: producers, processors, governments, nongovernmental organizations, and consumers.


Factors delaying discharge of psychiatric patients.
The reliable identification of patients at high risk of experiencing delays in discharge is an important objective of social workers in psychiatric settings. This study discovered a number of factors associated with excessive hospital stays, marking an initial step in the development of a list of high-risk indicators to be used to achieve more timely and appropriate transitions for psychiatric patients no longer in need of inpatient care.


Reactive ion etching of Si(x)Sb2Te in CF4/Ar plasma for nonvolatile phase-change memory device.
Si(x)Sb2Te material system is novel for phase-change random access memory applications. Its properties are more outstanding than the widely used material Ge2Sb2Te5. Etching process is one of the critical steps in the device fabrication. The etching characteristics of phase-change material Si(x)Sb2Te were studied with CF4/Ar gas mixture by a reactive ion etching system. The changes of etching rate, etching profile and surface root-mean-square roughness resulted from variation of the gas-mixing ratio were investigated under constant pressure (50 mTorr) and applying power (200 W). Si0.34Sb2Te is with the highest phase-change speed and the lowest power consumption in the PCRAM memory among these compositions, which means it is the most promising candidate for the PCRAM applications. So the most optimized CF4/Ar gas ratio for Si0.34Sb2Te was studied, the value is 25/25. The etching rate is 155 nm/min, and the selectivity of Si0.34Sb2Te to SiO2 is as high as 3.4 times. Furthermore, the smooth surface was achieved with this optimized gas ratio.


Microdentistry: current pit-and-fissure caries management.
The systemic application of fluoride has rendered enamel more resistant to decalcification and decay. While the incidence and severity of dental caries has decreased, the diagnosis of caries in this enamel environment has created significant new challenges and dilemmas. Traditional diagnostic methodology and treatment philosophy no longer seem appropriate. This article describes the historical perspectives, current diagnostic challenges, and the treatment dilemmas of occlusal pit-and-fissure systems currently facing the dental profession.


Studies on molybdenum absorption and transport in bean and rice.
The patterns of molybdenum (MoO(4) (2-)) absorption and transport were investigated in intact bean (Phaseolus vulgaris L.) and rice (Oryza sativa L. cv. I.R.8) plants. The mobility of MoO(4) (2-) absorbed by roots and by leaves was compared with that of a freely mobile element, Rb(+). Although MoO(4) (2-) absorption by bean roots was nearly as high as that of Rb(+), its transport to the shoot was considerably less. When MoO(4) (2-) was fed to one of the primary leaves, most of it was transported to the stem and root. Evidence obtained here showed that MoO(4) (2-) was mobile. Experiments with intact rice seedlings revealed large differences in the absorption and transport of MoO(4) (2-) between the plants grown in CaSO(4) and those in Hoagland solution. Molybdate uptake by excised rice roots was suggested to be an active process since it was greatly inhibited by a metabolic inhibitor. The presence of Mn(2+), Zn(2+), Cu(2+), CI(-), or SO(4) (2-) in the absorption medium reduced MoO(4) (2-) uptake which was markedly enhanced by the presence of Fe(2+).


Replicating patient-level moderators of CBT and IPT's comparative efficacy for depression.
Although evidence-based psychotherapies, such as cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT), produce comparable average outcomes, it is plausible that some patients who possess one or more specific characteristics may respond better to one over the other. Addressing this what works best for whom question, researchers have tested the moderating influence of patient characteristics on comparative treatment effects (viz. aptitude-treatment interactions [ATIs]). However, few ATIs have emerged or replicated, thereby providing little treatment-selection guidance. Informed by a systematic review of patient ATIs in trials that compared CBT versus IPT for depression (Bernecker et al., 2017), this study aimed to replicate (a) significant ATIs previously established in a single study; and (b) significant ATIs previously examined twice, with only one study demonstrating a moderating effect. Data derived from a trial in which adult outpatients with major depression were randomly assigned to 16 weeks of CBT (n = 41) or IPT (n = 39). Patient characteristics were measured at baseline, and patients rated their depression throughout treatment. Multilevel models revealed one ATI replication; for patients with more self-sacrificing interpersonal problems, CBT outperformed IPT; the reverse was true for patients with fewer such problems. Other moderators either failed to replicate or directionally contradicted prior research. Results help inform optimal treatment matching for some patients, which reflects a type of psychotherapy personalization. However, they also highlight limitations of traditional ATI research and suggest that different methods are needed to inform responsive personalization efforts more expansively and reliably. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Echocardiographic predictors of remote outcome in patients with angiographically successful reflow after acute myocardial infarction.
The angiographically no-reflow phenomenon after percutaneous coronary intervention (PCI) predicts poor left ventricular (LV) functional recovery and a high risk of cardiac events in patients with their first acute myocardial infarction (AMI). However, risk factors of long-term adverse outcome for patients with angiographically successful reflow (TIMI (Thrombolysis in Myocardial Infarction) flow grade 3) for the AMI remain unknown. Of 168 echocardiograms were performed before PCI and at discharge, 113 were suitable for analysis. Clinical, angiographic, and echocardiographic variables were submitted to statistical analysis to detect the risk factors of cardiac events. During the follow-up period of 46+/-20 months, 31 patients had cardiac events, though there were no cardiac deaths. The 2 most important risk factors for congestive heart failure (CHF) or total cardiac events were LV dilation (chi-square: 7.5 and 9.4; both p<0.01) and pseudonormal transmitral flow pattern (PN, chi-square: 4.9, p<0.05 and 6.7, p<0.01, respectively). However, only multivessel disease (chi-square: 9.4, p=0.05) became the predictor for revascularization after PCI. The incidence of CHF or total cardiac events in patients with PN and LV dilation at discharge determined by the Kaplan-Meier method were significantly higher than those with normal or abnormal relaxation transmitral flow pattern (log-rank: 41 and 27, both p<0.001) and no LV dilation (log-rank: 20 and 20, both p<0.001). Poor LV diastolic function and LV dilation at discharge are predictors of the cardiac events in patients in whom epicardial coronary flow was well-restored after PCI for the first AMI.


Genetic variability in the Guahibo population from Venezuela.
Four communities from Guahibo of Venezuela were analyzed for the genetic variants of nine erythrocyte enzymes and five serum proteins. Of the 14 loci determined, four were monomorphic. Significant frequency differentiation among communities, was present for ESD and TF markers. In general, Guahibo allele frequencies are in the variation ranges described for South American groups. The analysis indicates a relatively higher affinity of Guahibos with other Venezuelan groups within an irregular pattern of genetic distances that are likely related to the complex demographic history of the South American groups. Genetic diversity estimates reveal a moderate degree of genetic structure between the four Guahibo communities. This intra-tribal variability in Guahibo appears to be lower than in Venezuelan Piaroa but higher than in other Amerindians and could be attributed to a combined effect of low population size and relative isolation of communities. At a continental level, the distribution of genetic diversity is consistent with preferential population movements along the eastern and western coastal areas.


Pro-sequence-assisted protein folding.
Many proteins, including proteases and growth factors, are synthesized as precursors in the form of pre-pro-proteins. Whereas the pre-sequences usually act as signal peptides for transport, the pro-sequences of an increasing number of these proteins have been found to be essential for the correct folding of their associated proteins. In contrast to the action of molecular chaperones, pro-sequences appear to catalyse the protein-folding reaction directly. The similarity between the pro-sequence-assisted folding mechanisms of different proteases supports the hypothesis that a common folding mechanism has developed through convergent evolution. Further, the frequent requirement of the pro-sequences for both folding and intracellular transport or secretion suggests that these two functionalities are intimately related.


The piriformis muscle syndrome. Sciatic nerve entrapment treated with section of the piriformis muscle.
The piriformis muscle syndrome, a term applied to an abnormal condition of the piriformis muscle, is characterized by symptoms and signs due to sciatic nerve entrapment at the greater sciatic notch. Two patients with this syndrome, successfully treated with section of the piriformis muscle, are reported. The piriformis muscle syndrome should be suspected as part of the differential diagnosis in cases of low back and hip or thigh pain.


Limits of prenatal care coordination for improving birth outcomes among Medicaid participants.
Maternity Care Homes (MCHs) intend to address clinical and psychosocial needs for perinatal patients and are commonly implemented for Medicaid beneficiaries. Rigorous evidence supporting MCHs' effectiveness for improving birth outcomes is thin, but most studies consider only clinical and demographic factors from administrative data. To assess birth outcomes with controls for psychosocial variables known to affect them, this paper considers quantitative participant-level data from the Strong Start for Mothers and Newborns prenatal care initiative, with qualitative case study data to further contextualize results. From 2013 to 2017, Strong Start served over 45,000 Medicaid beneficiaries in 32 states, D.C., and Puerto Rico though MCHs, group prenatal care, or freestanding birth centers. Participant data included risks screens for food insecurity, depression, anxiety, pregnancy intention, and intimate partner violence, in addition to clinical and demographic information. After clinical, demographic and psychosocial risks were controlled in a regression model, Strong Start birth center participants showed significantly lower rates of preterm birth, low birthweight, and cesarean section relative to MCH participants (p < .01). In group prenatal care, White participants showed lower rates of preterm birth (p < .01) and Black participants showed lower rates of low birthweight (p < .05) relative to MCH participants. Strong Start participants reported appreciation for MCH care managers' support, but community and clinical referrals often had long waiting lists or were inaccessible. Transformative care models focusing on provider continuity, relationship building, and patient activation may offer more promise for improving birth outcomes than supplementing medical models with care management and other resources.


MASQOT-GUI: spot quality assessment for the two-channel microarray platform.
MASQOT-GUI provides an open-source, platform-independent software pipeline for two-channel microarray spot quality control. This includes gridding, segmentation, quantification, quality assessment and data visualization. It hosts a set of independent applications, with interactions between the tools as well as import and export support for external software. The implementation of automated multivariate quality control assessment, which is a unique feature of MASQOT-GUI, is based on the previously documented and evaluated MASQOT methodology. Further abilities of the application are outlined and illustrated. MASQOT-GUI is Java-based and licensed under the GNU LGPL. Source code and installation files are available for download at http://masqot-gui.sourceforge.net/


Umbilical hernia causing ventriculoperitoneal shunt dysfunction: illustrative cases.
When ventriculoperitoneal (VP) shunts and umbilical hernias coexist in the same patient, unique complications can occur. Typically, these are readily identified problems such as cerebrospinal fluid (CSF) fistulas or entrapment of the peritoneal catheter in the hernia. The authors present cases of two children whose VP shunt dysfunction resolved after repair of their umbilical hernias. The authors present two cases of infant patients with shunted hydrocephalus and umbilical hernias. In both cases, the patients presented with distal shunt malfunctions not due to infection. Their shunt function improved once the umbilical hernia was repaired by pediatric surgery. Neither has required shunt revision since umbilical hernia repair. Although there are case reports of VP shunts eroding through the umbilicus, developing CSF fistulas, or becoming trapped inside umbilical hernias, there is no case of VP shunt dysfunction caused by just the presence of an umbilical hernia. The authors suspect that the catheter may intermittently enter and exit the hernia. This may cause intermittent obstruction of the distal catheter, or inflammation in the hernia may occur that limits CSF absorption.


[Technical aspects, indications and results of 24-hour esophageal pH-monitoring].
Twenty four-hour esophageal pH-monitoring is considered as the gold standard for the diagnosis of gastroesophageal reflux disease. The aims of this review are to describe technical aspects, interprative modalities and normal values of esophageal pH data to determine the indications of esophageal pH-monitoring with special interest of the most established indications.


Determination of tryptophan in bee pollen and royal jelly by high-performance liquid chromatography with fluorescence detection.
A method for tryptophan analysis in bee pollen and royal jelly was developed using HPLC with fluorescence detection. To determine the free tryptophan in bee pollen and royal jelly, ultrasonic extraction was performed using water (pH 6.3)-acetonitrile (10:1, v/v) as extraction solvent. While determining the total tryptophan in these bee products, the method involves alkaline hydrolysis of the proteins with 4 mol/L sodium hydroxide at 110 degrees C for 20 h under anaerobic conditions. The operating conditions for the HPLC analysis were: Symmetry C(18) column (4.6 x 250 mm, 5 microm), 0.1% trifluoroacetic acid-methanol (75:25, v/v) as the mobile phase at a flow rate of 1.0 mL/min at 30 degrees C. The fluorescence detector was operated at an excitation wavelength of 280 nm and an emission wavelength of 340 nm. A linear response (r(2 )> 0.9998) was obtained in the range 0.0625-5.0 microg/mL. The method was successfully applied to the determination of the free and total tryptophan contents in bee pollens, which were 0.069 +/- 0.003 and 2.693 +/- 0.476 mg/g, respectively, while only the total tryptophan was detected in royal jelly, with a content of 1.743 +/- 0.066 mg/g.


[Non-surgical repair of atrial septal defect by "buttoned" double disk device in children. First results in 3 children].
Transcatheter closure of ostium secundum atrial septal defect (ASD) with a "buttoned" double-disk device was attempted in 5 children aged 14 months to 12 years, with success in 3 cases. The diameter of the ASD was 15 to 20 mm. The occluding devices were chosen with sizes 12-15 mm greater than those of the ASDs. There were no operative complications: the ASD was practically completely occluded in 2 children and left a very small shunt in a third case. Those three patients are doing well, 8 to 9 months after the procedure. In the other two cases, the device fell into the right atrium and had to be removed surgically without any complications. The "buttoned" double-disk device seems to be relatively simple and easy to insert through an 8F catheter. Additional technical improvements should enable more complete occlusion of ASD and easier retrieval by the transvenous route when incorrectly inserted. Further experimental and clinical studies are required to assess the results and to compare them with those of the other teams.


Gastro-cholecysto-colic fistula. Case report of an idiopathic case, and management approach.
A 71-year-old lady presented with a 4-week-history of epigastric pain, feculent vomiting, diarrhoea and weight-loss. On subsequent investigations, she was found to have a complex gastro-cholecysto-colic fistula with no clear underlying aetiology. The only abnormality both macroscopically and microscopically was ulceration and inflammation in the colon. However, this was not pathognomonic of inflammatory bowel disease, and (gastric) acid-induced inflammation is an alternative explanation. Herein we present her case, her comprehensive evaluation, her successful surgical management and a review of the relevant literature.


Fatigue microdamage in the radial predilection site for osteosarcoma in dogs.
To evaluate whether body size and anatomic site influence the quantity of bone microdamage in dogs without osteosarcoma (OS). Pairs of radii were collected from 10 small dogs (< 15 kg) and 10 large dogs (> 25 kg). Specimens were stained in basic fuchsin for bone microdamage. Transverse sections were cut from each proximal and distal radial metaphysis at 15 and 85% of bone length. The following variables were determined for each region: mean microcrack length (CrLe, microM), microcrack density (CrDn, microcracks/mm2), microcrack surface density (CrSDn, microm/mm2), and estimated activation frequency (Acf, microcracks/mm2/y). Metaphyseal region did not significantly influence CrDn, CrLe, and CrSDn. The CrDn and CrSDn were influenced by body size, with microdamage being increased in large dogs, compared with small dogs. However, mean CrLe was not significantly influenced by body size. Acf significantly decreased with age and was significantly decreased in large dogs and in the distal radial metaphysis, compared with small dogs and the proximal radial metaphysis, respectively. Our data did not reveal an increase in microdamage or remodeling at the OS predilection site (ie, the distal metaphysis of the radius), suggesting that induction of microdamage and an associated increase in bone remodeling are unlikely to be an important risk factor for induction of OS.


Pore structure, thinning effect, and lateral diffusive dynamics of oriented lipid membranes interacting with antimicrobial peptide protegrin-1: 31P and 2H solid-state NMR study.
Membrane pores that are induced in oriented membranes by an antimicrobial peptide (AMP), protegrin-1 (PG-1), are investigated by (31)P and (2)H solid state NMR spectroscopy. We incorporated a well-studied peptide, protegrin-1 (PG-1), a beta-sheet AMP, to investigate AMP-induced dynamic supramolecular lipid assemblies at different peptide concentrations and membrane compositions. Anisotropic NMR line shapes specifying toroidal pores and thinned membranes, which are formed in membrane bilayers by the binding of AMPs, have been analyzed for the first time. Theoretical NMR line shapes of lipids distributed on the surface of toroidal pores and thinned membranes reproduce reasonably well the line shape characteristics of our experimentally measured (31)P and (2)H solid-state NMR spectra of oriented lipids binding with PG-1. The lateral diffusions of lipids are also analyzed from the motionally averaged one- and two-dimensional (31)P and (2)H solid-state NMR spectra of oriented lipids that are binding with AMPs.


Ultrasonically estimated weight and gestational age. Predictors of neonatal respiratory distress syndrome.
Information from 504 women who had undergone real-time ultrasound examination within 72 hours of childbirth was used to evaluate the relationship between the product of ultrasonically estimated fetal weight (in kilograms) times ultrasonically estimated gestational age (in weeks) and neonatal morbidity and mortality. If this product was greater than 40, there were no neonatal deaths (excluding severe congenital abnormalities); if the product was greater than 80, there were no cases of significant respiratory distress syndrome. These data may prove to be highly useful in the rapid evaluation of preterm labor or other obstetric complications.


Sunitinib treatment promotes metastasis of drug-resistant renal cell carcinoma via TFE3 signaling pathway.
Receptor tyrosine kinase (RTK) inhibitors, such as sunitinib and sorafenib, remain the first-line drugs for the treatment of mRCC. Acquired drug resistance and metastasis are the main causes of treatment failure. However, in the case of metastasis Renal Cell Cancer (mRCC), which showed a good response to sunitinib, we found that long-term treatment with sunitinib could promote lysosome biosynthesis and exocytosis, thereby triggering the metastasis of RCC. By constructing sunitinib-resistant cell lines in vivo, we confirmed that TFE3 plays a key role in the acquired resistance to sunitinib in RCC. Under the stimulation of sunitinib, TFE3 continued to enter the nucleus, promoting the expression of endoplasmic reticulum (ER) protein E-Syt1. E-Syt1 and the lysosomal membrane protein Syt7 form a heterodimer, which induces ER fragmentation, Ca2+ release, and lysosomal exocytosis. Lysosomal exocytosis has two functions: pumping sunitinib out from the cytoplasm, which promotes resistance to sunitinib in RCC, releasing cathepsin B (CTSB) into the extracellular matrix (ECM), which can degrade the ECM to enhance the invasion and metastasis ability of RCC. Our study found that although sunitinib is an effective drug for the treatment of mRCC, once RCC has acquired resistance to sunitinib, sunitinib treatment will promote metastasis.


Shortcomings of the current TNM classification for penile carcinoma: time for a change?
Accurate tumor staging is essential in the management of malignancies. It provides a guide in selecting accurate treatment and gives an indication of prognosis based on the extent of disease. The current TNM classification for penile carcinoma has remained unchanged since 1987. In this article, we focus on several deficiencies of the current classification. An analysis of the current literature regarding the current classification was done, focusing on known prognostic factors for survival. Furthermore, we discuss in detail the results from a recent analysis of more than 500 patients treated at our institute to evaluate the practical and prognostic value of the TNM-classification. We found that, using the current classification system, accurate clinical staging is often difficult, because the T and N categories are defined by structures that are not easily identified using physical examination or imaging. Furthermore, the prognostic stratification of the present staging system is not optimal and there is a substantial overlap in disease-specific survival between several categories. We give an overview of modifications that could improve clinical staging and prognostic ability. The current TNM classification for penile carcinoma has several shortcomings in terms of usability in clinical staging and prognostic value. With modifications clinical staging is facilitated, while the prognostic stratification of the classification is improved.


Adjuvant high-dose interferon-alpha therapy for high-risk melanoma.
The incidence of melanoma continues to rise at a rate greater than all other cancers. Survival in melanoma varies widely by stage, and is affected by a number of prognostic factors including tumour thickness, ulceration and lymph node involvement. New AJCC staging criteria adopted in the 6(th) edition reflect the prognostic value of tumour ulceration, the number of positive lymph nodes as a better prognostic indicator than the size of nodal metastasis, and the similar prognostic value provided by nodal, in-transit and local recurrences. It also recognises the pathologic information about staging provided by lymphatic mapping and sentinel lymphadenectomy. High-risk resected melanoma is defined as disease that after surgery is at higher than 40 to 50% risk of recurrence and death. The urgency to the effort to develop effective therapy for melanoma has led to a wide variety of approaches that have been tested over the years in the high-risk adjuvant setting. Among the many therapeutic modalities tested, the only agent that has shown a significant and reproducible benefit in terms of survival and relapse-free interval has been high-dose interferon-alpha2b. We here review the evidence that has led to the regulatory approval of this regimen, as well as ongoing studies using high-dose interferon-alpha in the high-risk adjuvant setting. We also present selected ongoing trials testing potential future therapies that may prove effective for patients with high-risk resected melanoma.


Pediatric primary pilocytic astrocytoma of the cerebellopontine angle: a case report.
We describe a rare case of pediatric pilocytic astrocytoma presented as a right cerebellopontine angle (CPA) mass, completely separated from the brain stem and arising from the proximal VIII nerve portion. A 12-year-old boy, with no evidence of neurofibromatosis type 2, presented with progressive hearing loss at the right ear and headache. An initial enhanced magnetic resonance examination suggested the diagnosis of schwannoma. The tumor was resected by a suboccipital retrosigmoid approach. Our case seems to be the first report of a primary pediatric CPA pylocitic astrocytoma arising from the VIII nerve complex and presenting internal auditory canal enlargement. It represents the third reported case of a primary CPA pilocytic astrocytoma (the second pediatric case with the first arising from V nerve) and the eighth report of primary CPA glioma, overall. We discuss the clinical, neuroradiological, and intraoperative findings, and we review the different hypothesis about the origin of these rare tumors.


Liquid-chromatographic analysis for urinary porphyrins.
Urinary porphyrins are separated, according to number of carboxyl groups, in a system consisting of a mu-Bondapak C18 stationary phase and a mobile phase of methanol and aqueous sodium phosphate (pH 3.5) in a linear gradient. The specimen is prepared simply by adjusting the pH of a 5-mL sample to 2.0 and removing solids by centrifugation. The eluted porphyrins are measured fluorometrically. Naturally occurring non-porphyrin fluorescent substances are eluted ahead of the porphyrins. Chromatography requires about 20 min, and a re-establishment of initial conditions requires an additional 15 min.


[Two cases of stromal sarcoma, so-called malignant fibrous histiocytoma of breast treated with reduction surgery].
CASE 1: A 64-year-old woman with right breast cancer had a partial mastectomy and radiotherapy four years ago was admitted to our hospital because of right breast mass. The vacuum associated biopsy of tumor resulted in breast sarcoma, thus a nipple-spearing mastectomy was performed. The final histological diagnosis was stromal sarcoma, and was identical to histological findings of malignant fibrous histiocytoma. Three months after the operation, a chest wall recurrence appeared. Although tumor resection with latissimus dorsi flap was performed, there were pleural dissemination and malignant pleural effusion. She died six months after the first surgery. CASE 2: A 60-year-old woman was admitted to our hospital because of left breast mass, but she refused a further clinical examination. She readmitted fourteen months later due to a huge sized left breast mass with necrosis and smelling discharge. CT scan showed a huge tumor of left breast and multiple lung metastases. Biopsy of the tumor resulted in breast sarcoma. Total mastectomy with split thickness skin grafting was performed. The final histological diagnosis was identical to the first case. A local recurrence appeared thirty days after the operation, and she died fifty-one days after the operation.


[Metabolic pathway and metabolites of total diterpene acid isolated from Pseudolarix kaempferi].
The preliminary metabolic profile of total diterpene acid (TDA) isolated from Pseudolarix kaempferi was investigated by using in vivo and in vitro tests. Pseudolaric acid C2 (PC2) was identified as the predominant metabolite in plasma, urine, bile and feces after both oral and intravenous administrations to rats using HPLC-UV and HPLC-ESI/MS(n), and demethoxydeacetoxypseudolaric acid B (DDPB), a metabolite proposed to be the glucoside of PC2 (PC2G), as well as pseudolaric acid C (PC), pseudolaric acid A (PA), pseudolaric acid A O-beta-D glucopyranoside (PAG), pseudolaric acid B O-beta-D glucopyranoside (PBG) and deacetylpseudolaric acid A (DPA) originated from TDA could also be detected. It was demonstrated by tests that the metabolism of TDA is independent of intestinal microflora, and neither of pepsin and trypsin is in charge of metabolism of TDA, TDA is also stable in both pH environments of gastric tract and intestinal tract. The metabolites of TDA in whole blood in vitro incubation were found to be PC2, DDPB and PC2G, which demonstrated that the metabolic reaction of TDA in vivo is mainly occurred in blood and contributed to be the hydrolysis of plasma esterase to ester bond, as well as the glucosylation reaction. These results clarified the metabolic pathway of TDA for the first time, which is of great significance to the in vivo active form and acting mechanism research of P. kaempferi.


Mesiobasal versus lateral temporal lobe epilepsy: metabolic differences in the temporal lobe shown by interictal 18F-FDG positron emission tomography.
Metabolic abnormalities in the temporal lobe (TL) of 25 patients suffering from temporal lobe epilepsy of mesiobasal or lateral TL origin have been investigated using interictal [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). The epileptogenic area was determined by ictal EEG recordings using foramen ovale and scalp electrodes in 20 patients, and by the use of stereo-electroencephalography in one patient. Four patients with structural lesions on their MRIs had noninvasive ictal surface EEG recordings. Sixteen patients had a clear-cut mesiobasal seizure onset, and in five patients the seizures originated from the lateral temporal neocortex. Twenty-four patients underwent selective surgery. Patients with temporal limbic seizures associated with mesial gliosis (n = 15) had the lowest FDG uptake in the entire TL, followed by patients with lateral temporal seizure origin (n = 5). Patients with tumors located in the mesiobasal TL (n = 5) showed, in general, only a slight decrease of glucose metabolism in all TL structures. There was no clear-cut correlation between the degree of hypometabolism and the location of EEG-defined epileptogenic focus. The metabolic pattern, however, differed between the patient groups and allowed a discrimination between patients of mesial temporal and lateral temporal seizure onset.


Quantitative SERRS immunoassay for the detection of human PSA.
We report the first use of a commonly used ELISA colorimetric substrate as a SERRS marker and show how it can be used for the detection of pg ml(-1) levels of human prostate specific antigen (PSA) in clinical samples. The technique is amenable over a wide range of concentrations and lends itself to future multiplexing analysis.


AFM sensing cortical actin cytoskeleton destabilization during plasma membrane electropermeabilization.
Electropermeabilization is a physical method that uses electric field pulses to deliver molecules into cells and tissues. Despite its increasing interest in clinics, little is known about plasma membrane destabilization process occurring during electropermeabilization. Having previously demonstrated the usefulness of Atomic Force Microscopy to study electropermeabilization effect on plasma membrane, we further investigated the plasma membrane destabilization process. We got mainly interested in the cytoskeleton role in stiffness of the plasma membrane, and thus in the effect of electric field on the cortical actin network. We show here that cortical actin is destabilized by electric pulses and that this effect is not directly related to the electropermeabilization of the plasma membrane.


Task-Sharing Between Pediatricians and Non-Physician Healthcare Professionals in Outpatient Child Health Care in Germany: Assessment of Need and Acceptance for Concept Development.
Although pediatricians in Germany work as general practitioners for children, they are planned and trained as medical specialists. In consequence, distances between practices and residences of patients can be very large. The implementation of task-sharing models is a promising option to sustain pediatric outpatient care in rural regions. In this study we assessed the need for and acceptance of delegation of tasks in outpatient pediatric healthcare to non-physician healthcare professionals and developed a task-sharing concept. A standardized questionnaire was developed and addressed a wide range of healthcare professionals. On the basis of the results of the questionnaire and a subsequent workshop involving representatives of the various fields of pediatric care a delegation-concept was developed. A total of 206 questionnaires were answered (response rate: 17%). About 70% of the respondents (n = 145) agreed with the delegation of counseling on prevention, 66% (n = 135) with the delegation of tasks in the transition process into adult medicine. All proposed tasks were conceivable for at least a third of the respondents. Mostly, pediatricians could envision delegation more than the non-physician health care professionals. A three-dimension-delegation-concept was developed: which tasks can be delegated to whom in which setting. Basically, if nurses or medical practice assistants are adequately qualified, all tasks can be delegated to both. The delegation was approved by most of the respondents. Implementation of task-sharing provides a new option to support pediatricians and create better access to outpatient pediatric health care in rural regions. The next step should be the implementation of the delegation concept in pilot projects.


[Levels of amino acids in cerebral spinal fluid in children with cerebral palsy].
To study the changes of amino acids in cerebral spinal fluid (CSF) in children with spastic or athetotic cerebral palsy (CP) by examining CSF levels of glutamic acid (Glu), gamma-aminobutyric acid (GABA) and aspartate (ASP). CSF samples were obtained from 13 children with spastic CP, from 14 children with athetotic CP, and from 10 children without central nervous system and infectious diseases (control group). CSF levels of Glu, GABA and ASP were determined by high-performance liquid chromatography. CSF levels of GABA, ASP and Glu in the control group were 13.04+/-2.19, 10.21+/-0.45 and 8.41+/-2.26 micromol/L, respectively. Compared with the control group, CSF GABA levels in the spastic and the athetotic CP groups (8.02+/-2.03 and 10.01+/-2.68 micromol/L respectively) significantly decreased (P<0.01), whereas CSF levels of Glu (20.99+/-8.15 and 28.77+/-17.62 micromol/L respectively) and Asp (13.53+/-3.93 and 14.02+/-2.88 micromol/L respectively) in the spastic and the athetotic CP groups significantly increased (P<0.01). There were statistical differences in the GABA level between the spastic and the athetotic CP groups (P<0.05). In children with spastic CPCSF Glu level was positively correlated to muscle tension. CSF excitatory amino acid levels increased, while CSF inhibitory amino acid levels decreased in children with CP. There were differences for CSF amino acid levels in different types of CP. The changes of amino acid levels may contribute to the pathogenesis of CP.


Structural Transition-Induced Raman Enhancement in Bioinspired Diphenylalanine Peptide Nanotubes.
Semiconducting materials are increasingly proposed as alternatives to noble metal nanomaterials to enhance Raman scattering. We demonstrate that bioinspired semiconducting diphenylalanine peptide nanotubes annealed through a reported structural transition can support Raman detection of 10-7 M concentrations for a range of molecules including mononucleotides. The enhancement is attributed to the introduction of electronic states below the conduction band that facilitate charge transfer to the analyte molecule. These results show that organic semiconductor-based materials can serve as platforms for enhanced Raman scattering for chemical sensing. As the sensor is metal-free, the enhancement is achieved without the introduction of electromagnetic surface-enhanced Raman spectroscopy.


A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension.
Kinetochores play an essential role in chromosome segregation by forming dynamic connections with spindle microtubules. Here, we identify a set of 10 copurifying kinetochore proteins from Caenorhabditis elegans, seven of which were previously uncharacterized. Using in vivo assays to monitor chromosome segregation, kinetochore assembly, and the mechanical stability of chromosome-microtubule attachments, we show that this copurifying protein network plays a central role at the kinetochore-microtubule interface. In addition, our analysis suggests that the network is comprised of three groups of proteins that contribute in distinct ways to this interface: KNL proteins act after the assembly of centromeric chromatin to generate the core of the microtubule-binding interface, MIS proteins control the rate and extent of formation of this interface, and NDC proteins are necessary to sustain tension during interactions with spindle microtubules. We also purify a similar set of associated proteins from human cells that includes four novel proteins and has recognizable homologs from each functional class. Thus, this protein network is a conserved constituent of the outer kinetochore, and the functions defined by our analysis in C. elegans are likely to be widely relevant.


Sedentary Behavior, Physical Activity, and Bone Health in Postmenopausal Women.
The purpose of this study was to determine if bone health at the femoral neck (FN) and lumbar spine (LS) can be predicted from objectively-measured sedentary behavior and physical activity data in postmenopausal women. Waist-mounted ActiGraph GT1M and GT3X devices were used to quantify levels of sedentary and moderate-to-vigorous intensity behavior during a 7-day period in 44 older females. Bone health (normal and osteopenia/osteoporosis) of FN and LS was derived from T scores generated using dual energy x-ray absorptiometry. Binomial logistic regression analysis indicated that sedentary time and number of breaks in sedentary behavior were significant predictors of osteopenia/osteoporosis at the FN, but not at the LS. Adherence to physical activity guidelines was not a significant predictor of bone health at the FN or LS. Our findings suggest that more frequent interruptions in sedentary behavior are associated with improved bone health in postmenopausal women.


Reversal of chronic ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade.
Teenage drinking continues to be a significant problem in the U.S., as well as abroad. We have previously demonstrated that opiate blockade with naltrexone, a drug currently used in patients to diminish alcohol craving, prevented the fall in serum testosterone seen after acute ethanol (EtOH) exposure in young, peripubertal male rats. To follow-up on this reversal, a series of experiments was performed to determine if naltrexone would also prevent the testosterone suppression caused by chronic EtOH exposure. Peripubertal rats either 45 days old (mid-pubertal) or 55 days old (late pubertal) were fed an EtOH-containing liquid diet or pair-fed control diet for 14 days. Each animal was implanted with either a naltrexone containing or placebo pellet before starting the liquid diet. In each age group, EtOH alone significantly suppressed testosterone, whereas naltrexone prevented this fall, although it had no effect alone. Serum luteinizing hormone was also suppressed by EtOH; however, naltrexone did not abrogate this fall. In the 45-day-old animals, beta-luteinizing hormone mRNA levels rose significantly in the EtOH group, but not when naltrexone was coadministered with EtOH. There was no change in hypothalamic luteinizing hormone releasing hormone (LHRH) mRNA, pro-LHRH, or LHRH in any group at either age. Thus, naltrexone is able to partially prevent the EtOH-induced suppression of gonadal testosterone of young, adolescent male rats. This effect appears to be mediated directly at gonadal level, because hypothalamic and pituitary hormone changes were minor and nonsignificant.


IgG4-related disease causing facial nerve and optic nerve palsies: Case report and literature review.
IgG4-related disease (IgG4-RD) is increasingly being recognized as an entity effecting the head and neck region. Although most commonly seen with salivary gland or paranasal sinus involvement, IgG4-RD may also involve the temporal bone and skull base. We report a rare care of a 61-year-old female with IgG4-RD presenting as synchronous lesions of the middle ear and middle cranial fossa with polyneuropathy of cranial nerves II, VI, and VII. Initial histopathological evaluation of her resected ear mass suggested a benign inflammatory process but no specific diagnosis. Her symptoms progressed over 10months prompting re-evaluation of the specimen and consideration of the IgG4-RD diagnosis. Key pathologic features included prominent lymphoplasmacytic population, storiform fibrosis, obliterative phlebitis, and IgG4 specific staining. The patient was treated with high-dose intravenous and oral steroids but was transitioned to azathioprine secondary to steroid-induced myopathy. Radiographic studies before and after treatment reveal marked improvement of the intracranial and extracranial disease. Correspondingly, her cranial neuropathies resolved. A high degree of clinical suspicion is necessary to diagnosis IgG4-RD. The diagnosis can be supported by elevated serum IgG, elevated IgG index, and pathognomonic histopathological findings. Primary treatment is with corticosteroids. However, immunotherapy using azathioprine or rituximab can be utilized in recurrent disease or patients with steroid intolerance.


Systemic Therapy for Resected Pancreatic Adenocarcinoma: How Much is Enough?
Systemic therapy is an essential part of treatment for pancreatic ductal adenocarcinoma (PDAC). However, not all patients receive every cycle of chemotherapy and even if they do, the impact of reduced dose density (DD) on survival is not known. A single institutional prospective database was queried for patients with PDAC who underwent curative resection between 2009 and 2018. The primary outcome was DD, defined as the percentage of total planned chemotherapy actually received and associated survival. Of the 126 patients included, 38.9% underwent a neoadjuvant approach, which was associated with a greater median number of completed chemotherapy cycles (5 cycles versus 4 cycles, p < 0.01) and a higher median total DD (93.0% versus 65.0%, p < 0.01), compared with an adjuvant treatment approach. In both groups, adjuvant chemotherapy completion rates were low, with only 55 patients completing all adjuvant cycles. After sequential survival analysis, patients who received a DD ≥ 80% had improved median overall survival (OS) (27.1 months versus 18.6 months, p = 0.01), compared with patients who achieved a DD < 80%. On multivariate Cox proportional-hazards modeling, only the presence of lymphovascular invasion (HR: 1.77, 95% CI: 1.04-2.99, p = 0.04) and DD < 80% (HR: 1.91, 95% CI: 1.23-3.00, p = 0.01) were associated with decreased OS. In this cohort study, patients who received ≥ 80% DD had significantly better OS. DD should be considered an important prognostic metric in pancreatic cancer, and strategies are needed to improve chemotherapy tolerance to improve patient outcomes.


Stability, Interfacial Structure, and Gastrointestinal Digestion of β-Carotene-Loaded Pickering Emulsions Co-stabilized by Particles, a Biopolymer, and a Surfactant.
Novel Pickering emulsions were stabilized by complex interfaces in the presence of zein colloidal particles (ZCPs), propylene glycol alginate (PGA), and rhamnolipid (Rha) for delivery of β-carotene. The influence of the particle-surfactant, particle-biopolymer, and particle-biopolymer-surfactant mixed interfaces on the physiochemical properties and digestion fate of Pickering emulsions was investigated. It is the first time that three different types of emulsifiers have been used to synergistically stabilize food Pickering emulsions for delivery of lipophilic nutraceuticals. The physicochemical stability, microstructure, rheological properties, and in vitro gastrointestinal digestion of Pickering emulsions were controlled by the addition sequence and mass ratio of multiple stabilizers, which showed the enhanced stability and delayed lipid digestion of the particle-biopolymer-surfactant-stabilized Pickering emulsions. After encapsulation into Pickering emulsions, the retention rate of β-carotene increased 2-fold under UV radiation for 8 h. The coexistence of ZCPs, PGA, and Rha could induce the competitive displacement, multilayer deposition, and interparticle network at the interface. The combination of particles, a biopolymer, and a surfactant delayed the lipolysis during in vitro gastrointestinal tract. By modulating the interfacial composition, the release rate of free fatty acids from Pickering emulsions was reduced from 19.46% to 2.83% through different mechanisms. The novel Pickering emulsion could be incorporated in foods as well as pharmaceuticals for controlled lipid digestion or targeted nutrient delivery purposes.


Diagnostic pitfalls in fine-needle aspiration cytology of temporomandibular chondroblastoma: report of two cases.
Chondroblastoma is a benign bone neoplasm, which usually presents in the epiphysis of long bones, but can occur in unusual locations. This report describes the clinical, radiologic, and cytologic features on FNA of two chondroblastomas of the temporomandibular region that were only recognized by histopathologic study. This emphasizes the diagnostic pitfalls of this entity and expands the cytologic differential diagnosis of tumors of the parotid region.


Mammalian Bites In The Emergency Department: Recommendations For Wound Closure, Antibiotics, And Postexposure Prophylaxis.
Half of all Americans will experience a mammalian bite at some time in their life, and the cost of caring for these injuries has reached $160 million annually. Emergency clinicians must consider many factors when making decisions regarding care of these injuries: risk of infection, cost of antibiotics, time of wound healing, cosmetic and functional result, and risk of other injuries or diseases. Knowledge of the current literature and practice guidelines facilitates care for these injuries in the most cost-effective and clinically sound manner. This systematic review provides best-practice recommendations based on the best available evidence.


Developmental complexity of early mammalian pluripotent cell populations in vivo and in vitro.
Early mammalian embryogenesis is characterised by the coordinated proliferation, differentiation, migration and apoptosis of a pluripotent cell pool that is able to give rise to extraembryonic lineages and all the cell types of the embryo proper. These cells retain pluripotent differentiation capability, defined in this paper as the ability to form all cell types of the embryo and adult, until differentiation into the three embryonic germ layers at gastrulation. Our understanding of pluripotent cell biology and molecular regulation has been hampered by the difficulties associated with experimental manipulation of these cells in vivo. However, a more detailed understanding of pluripotent cell behaviour is emerging from the application of molecular technologies to early mouse embryogenesis. The construction of mouse mutants by gene targeting, mapping of gene expression in vivo, and modelling of cell decisions in vitro are providing insight into the cellular origin, identity and action of key developmental regulators, and the nature of pluripotent cells themselves. In this review we discuss the properties of early embryonic pluripotent cells in vitro and in vivo, focusing on progression from inner cell mass (ICM) cells in the blastocyst to the onset of gastrulation.


Maturation-dependent oligodendrocyte apoptosis caused by hyperoxia.
In the immature human brain, periventricular leukomalacia (PVL) is the predominant white matter injury underlying the development of cerebral palsy. PVL has its peak incidence during a well-defined period in human brain development (23-32 weeks postconceptional age) characterized by extensive oligodendrocyte migration and maturation. We hypothesized that the dramatic rise of oxygen tissue tension associated with mammalian birth and additional oxygen exposure of the preterm infant during intensive care may be harmful to immature oligodendrocytes (OLs). We therefore investigated the effects of hyperoxia on rat oligodendroglia cells in vitro and in vivo. Immature OLs (OLN-93), their progenitors [preoligodendrocytes (pre-OL)], and mature OLs were subjected to 80% hyperoxia (24-96 hr). Flow cytometry was used to assess cell death. Cell viability was measured by metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT). In addition, 6-day-old rat pups were subjected to 80% oxygen (24 hr) and then sacrificed, and their brains were processed for immunfluorescence staining. Apoptosis was detected at various stages (annexin-V, activated caspase-3) after 24-48 hr of incubation in 80% oxygen in pre- and immature OLs. Mature OLs were resistant to oxygen exposure. These results were confirmed by MTT assay. This cell death was blocked by administration of the pan-caspase inhibitor zVAD-fmk. Degeneration of OLs was confirmed in 7-day-old rat brains by positive staining for activated caspase-3. Hyperoxia triggers maturation-dependent apoptosis in immature and pre-OLs and involves caspase activation. This mechanism may be relevant to the white matter injury observed in infants born preterm.


Cloning and characterization of root-specific barley lectin.
Cereal lectins are a class of biochemically and antigenically related proteins localized in a tissue-specific manner in embryos and adult plants. To study the specificity of lectin expression, a barley (Hordeum vulgare L.) embryo cDNA library was constructed and a clone (BLc3) for barley lectin was isolated. BLc3 is 972 nucleotides long and includes an open reading frame of 212 amino acids. The deduced amino acid sequence contains a putative signal peptide of 26 amino acid residues followed by a 186 amino acid polypeptide. This polypeptide has 95% sequence identity to the antigenically indistinguishable wheat germ agglutinin isolectin-B (WGA-B) suggesting that BLc3 encodes barley lectin. Further evidence that BLc3 encodes barley lectin was obtained by immunoprecipitation of the in vitro translation products of BLc3 RNA transcripts and barley embryo poly(A(+)) RNA. In situ hybridizations with BLc3 showed that barley lectin gene expression is confined to the outermost cell layers of both embryonic and adult root tips. On Northern blots, BLc3 hybridizes to a 1.0 kilobyte mRNA in poly(A(+)) RNA from both embryos and root tips. We suggest, on the basis of immunoblot experiments, that barley lectin is synthesized as a glycosylated precursor and processed by removal of a portion of the carboxyl terminus including the single N-linked glycosylation site.


Transphobia and gender identity: social representations of trans women from Brazil and Colombia.
The present research aimed to identify and discuss the social representations of trans women related to gender identity and transphobia in Brazil and Colombia. In this study participated 43 Trans women, 22 from Brazil, aged between 18 and 55 years (M=29.09, SD=8.53) and 21 from Colombia, aged between 21 and 41 years (M=28.19, SD=7.63). This study adopted a qualitative approach in which semi-structured interviews were used. The data were analyzed by the Iramuteq software, which identified the social representations in classes. The results showed what the participants understood about transphobia and how they regarded their experiences with this gender identity. The participants presented negative social representations, aiming at their personal experiences related to their social context. Themes related to violence, discrimination, prejudice, denial of rights and family support emerged from both the Brazilian and Colombian sample. Implications for Tran´s quality of life are discussed.


Seasonal variations in the biochemical composition and reproductive cycle of the ghost crab Ocypode quadrata (Fabricius, 1787) in Southern Brazil.
The ghost crab, Ocypode quadrata, is found on sandy beaches from the United States to Southern Brazil. Because there is still little information about the metabolism and reproduction of O. quadrata on the southern coast of Brazil, the objectives of this study were to (i) evaluate the effect of seasonal variations on the carbohydrate, lipid, and protein metabolism of O. quadrata at Rondinha Beach, a beach with high anthropogenic activity, and to compare it with data from Siriú Beach, which has less human activity; and (ii) describe the effect of seasonal variations on the histological characteristics of male and female gonads, in order to assess the reproductive capacity of the crabs. The gonads of male crabs showed no significant variations in the gonadosomatic index (GSI) and glycogen levels; however, histological analysis of the testes revealed that they are mature in the summer. In females, the GSI and glycogen values are higher in summer, concomitantly with the presence of mature oocytes. These results suggest that the reproductive peak of O. quadrata occurs in summer. The seasonal analysis of the biochemical parameters, as well as comparison with Siriú Beach, demonstrated that the ghost crabs of Rondinha Beach have a different pattern of metabolism than those of Siriú. This difference may be a consequence of differences in the environmental conditions as well as in the anthropogenic pressures, such as vehicle traffic and the increase in human population at the beach in summer.


Biomechanics of the Injured Fibula Following Plate Fixation of a Concomitant Tibia Fracture To Fix or Not to Fix?
The mechanical role of supplemental fibula fixation in both bone lower leg fractures is not well defined. The benefit of fibula plate fixation in this context is controversial. The purpose of this study was to ascertain the mechanical contributions of the fibula under three conditions (intact, fractured, or plated fibula) following standard tibia locked plating. A laboratory fracture model was created with 10 cadaveric legs (5 matched pairs) with no known history of lower extremity trauma or other musculoskeletal conditions. A both bone lower leg fracture was simulated by performing distal osteotomies, 3 to 5 cm above the tibia plafond, leaving a bony defect to simulate an unstable fracture (AOTrauma OTA classification 43-A3). Coronal and sagittal gauge-pins were placed above and below the fracture sites to measure relative displacement across three planes of motion. Axial and torsional loads were applied to the leg under the following conditions: tibia intact and fibula intact (control 1), tibia fracture and fibula intact, tibia fracture and fibula fracture (control 2), and the three conditions of primary interest: tibia plated and fibula intact, tibia plated and fibula fracture (osteotomy), and tibia plated and fibula plated. The load applied for level 1 was 75 N of axial compression and 0.3 Nm of torque, and the load for level 2 was 175 N of axial compression and 1.3 Nm of torque. There were significant differences in motion across the fracture site of the injured leg when the tibia was not plated compared with an intact and plated tibia, p < 0.05. However, when the tibia was plated, there were no significant differences in fracture motion when the fibula was left either intact, osteotomized, or underwent supplemental plate fixation, p > 0.05. This was true regardless of the loads applied. The mechanical stability of supplemental fibula fixation in a both bone lower leg fracture model was not significantly improved from standalone distal tibia fixation in this laboratory model. The clinical effects of these findings are yet to be demonstrated.


Outcome versus service based payments in health care: lessons from African traditional healers.
We compare the more common physician compensation method of fee-for-service to the less common payment-for-outcomes method. This paper combines an investigation of the theoretical properties of both of these payment regimes with a unique data set from rural Cameroon in which patients can choose between outcome and service based payments. We show that consideration of the role of patient effort in the production of health leads to important differences in the performance of these contracts. Theory and empirical evidence show that when illnesses require (or are responsive to) large amounts of both patient and practitioner effort, outcome based payment schemes are superior to effort based schemes. The traditional healer--a practitioner who offers health services on an outcome-contingent basis--is advanced as an important example of how patient effort can be better understood and tapped in health care.


Recent Advances in Endometrial Cancer.
Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer.


Acute and chronic tendinopathies at the elbow.
Chronic elbow tendinitis (medial or lateral epicondylitis and triceps tendinitis) are common disorders that, overall, have a good prognosis but, even with optimum management, require a minimum of 3 to 6 months to resolve. Patient education, activity modification, splinting, and corticosteroid injections each serve a role in symptom resolution; surgery is required in less than 10% of cases and has a similarly long period (3 to 6 months) of recovery. Acute tendon injuries (biceps and triceps ruptures) require early (< 4 weeks) surgical repair but may be misdiagnosed, thus delaying management and requiring more involved surgical reconstruction. With appropriate treatment, the prognosis for each of these disorders is very good.


Probing the Energetics of Antigen-Antibody Recognition by Titration Microcalorimetry
Our understanding of the energetics that govern antigen-antibody recognition lags behind the increasingly rapid accumulation of structural information on antigen-antibody complexes. Thanks to the development of highly sensitive microcalorimeters, the thermodynamic parameters of antigen-antibody interactions can now be measured with precision and using only nanomole quantities of protein. The method of choice is isothermal titration calorimetry, in which a solution of the antibody (or antigen) is titrated with small aliquots of the antigen (or antibody) and the heat change accompanying the formation of the antigen-antibody complex is measured with a sensitivity as high as 0.1 μcal s-1. The free energy of binding (DeltaG), the binding enthalpy (DeltaH), and the binding entropy (DeltaS) are usually obtained from a single experiment, and no spectroscopic or radioactive label must be introduced into the antigen or antibody. The often large and negative change in heat capacity (DeltaCp) accompanying the formation of an antigen-antibody complex is obtained from DeltaH measured at different temperatures. The basic theory and the principle of the measurements are reviewed and illustrated by examples. The thermodynamic parameters relate to the dynamic physical forces that govern the association of the freely moving antigen and antibody into a well-structured and unique complex. This information complements the static picture of the antigen-antibody complex that results from X-ray diffraction analysis. Attempts to correlate dynamic and static aspects are discussed briefly.


A description of lactation counseling practices that are used with obese mothers.
Maternal overweight and obesity are associated with failure to initiate breastfeeding successfully and to sustain breastfeeding adequately. The purpose of this study was to describe how health care providers counsel obese mothers about breastfeeding. The authors surveyed (by telephone or in-person interview) health care providers who counsel mothers about breastfeeding in rural upstate New York (n = 89). They also surveyed lactation consultants (n = 31) from New York, New Jersey, Florida, Nebraska, California, and Texas by e-mail. The authors found that the majority of health care providers surveyed neither believed that there was a difference in the success rate between obese mothers and normal-weight mothers nor advised obese mothers differently about breastfeeding. Given the excess risk for premature lactation failure among obese women, these findings suggest that those who care for such women need to be made aware of this risk so that they can develop and provide appropriate services.


Comparison of Telemedicine Versus In-Person Visits on Impact of Downstream Utilization of Care.
Background: Telemedicine use has expanded substantially in recent years. Studies evaluating the impact of telemedicine modalities on downstream office visits have demonstrated mixed results. Introduction: We evaluated insurance claims of a large commercial payer, Blue Cross Blue Shield of Michigan (BCBSM), to assess the frequency of follow-up visits following encounters initiated via telemedicine versus in-person. Materials and Methods: We used the BCBSM claim-level data set (2011-2017) to assess encounters in the following places of service: hospital outpatient, doctor's office, patient's home, or psychiatric daycare facility. We identified the primary diagnostic category for 30-day episodes of care using clinical classifications software (CCS) and multilevel clinical classifications software (ML-CCS). Our intervention group consisted of episodes initiated via telemedicine; our control group consisted of episodes initiated in-person. Our primary outcome was the percentage of 30-day episodes with a related visit (encounters occurring within the same period and CCS categories) across CCS categories. Our secondary outcome was the mean related visit rate. Results: The final data set included 4,982,456 patients and 68,148,070 claims, of which 53,853 were telemedicine related. Many episodes did not have related visits (the mean related visit rate was 16%). Telemedicine visits had a higher frequency of related visits across all CCS categories. Discussion: Episodes of care initiated via telemedicine more frequently generate related visits within a 30-day period. This increased health care utilization could represent excessive care or could reflect expanded access to care. Conclusion: Further research should explore the cause of this increased utilization and potential unintended consequences.


Model-free parameters from dynamic contrast-enhanced-MRI: sensitivity to EES volume fraction and bolus timing.
To quantify the unknown relative sensitivities of semiquantitative measures from dynamic contrast-enhanced (DCE) MRI to variations in the volume fraction V(e) of the extravascular extracellular space (EES), and the duration of the contrast injection. Tissue-uptake curves were simulated across various values of F, PS, V(e), and bolus timings, with and without additive noise and at different image reacquisition rates. From each, the peak of the first derivative (G(peak)), the total uptake after the rapid first phase (CE), and the IAUC were calculated and plotted against F for each experimental condition. Relationships between each measure and the corresponding quantitative measure K(trans) were also examined, particularly for linearity. The highest sensitivity to flow was achieved for shorter bolus timings for G(peak), CE, and IAUC. G(peak) and IAUC were most linearly related to K(trans). The sensitivity to V(e) was lowest for G(peak), followed by IAUC and CE. Long sampling intervals resulted in severe underestimation of G(peak), while IAUC was unaffected provided that the limits of integration were properly applied. G(peak) could not be properly calculated in the presence of noise without a prior smoothing of the acquired curves, while IAUC was again unaffected by noise. G(peak) and IAUC are both useful model-free analogs of blood flow (i.e., K(trans)) for pre- and posttreatment comparisons. G(peak) may be the better choice in cases where larger changes in V(e) are likely, but only if sufficient noise reduction and fast image sampling are applied. If V(e) is expected to remain stable, IAUC is superior to G(peak) by virtue of its stability in the face of noise and more reliable estimation over a wider range of sampling rates.


Effects on carbon storage of conversion of old-growth forests to young forests.
Simulations of carbon storage suggest that conversion of old-growth forests to young fast-growing forests will not decrease atmospheric carbon dioxide (CO(2)) in general, as has been suggested recently. During simulated timber harvest, on-site carbon storage is reduced considerably and does not approach old-growth storage capacity for at least 200 years. Even when sequestration of carbon in wooden buildings is included in the models, timber harvest results in a net flux of CO(2) to the atmosphere. To offset this effect, the production of lumber and other long-term wood products, as well as the life-span of buildings, would have to increase markedly. Mass balance calculations indicate that the conversion of 5 x 10(9) to 1.8 x 10(9) megagrams of carbon to the atmosphere.


[Gastroesophageal patching with a jejunal loop in subtotal resections of the stomach].
The authors present a technical variant for re-establishing transit following sub-total gastric resections performed for extensive juxta-cardial lesions in which exeresis on the gastric wall also involves the right side of the terminal oesophagus. A "patch" of anastomotic jejunal loop is used in which the right segment of the assembly (the oesophagus and the right side of the gastric portion) does not take a direct part to the formation of the stoma. Two cases of gastric carcinoma are presented in which the extension of the lesions made necessary a strictly oesocardial proximal sectioning. The technique provides a wide stoma, without any risks of oesocardial obstruction. The method can be used in the gastric ulcers that are sited immediately under the cardia, allowing a sub-total resection with extirpation for the lesion. The authors suggest the use of this technique for the lesions high on the small curvature that cannot be extirpated with the classical technique due to the risk of stenosis of the cardial stoma as a result of the preparation of the oeso-cardial assembly. In this way the disadvantages of the exclusion technique introduced by Kelling and Madlener are avoided, as well as the risks of the high polar gastrectomy practiced by the Deloyers technique.


Reference Intervals for Urine Sediment Analysis of Healthy Pregnant Women.
Urine sediment parameters of pregnant women are different from those of non-pregnant women, and it is necessary to establish reference intervals for pregnant women. The aim of this study was to establish reference intervals of white blood cell (WBC), red blood cell (RBC), bacteria (BACT), squamous epithelial cell (EC), small round epithelial cell (SRC), and mucous strands (MUS) for urine sediment test of pregnant women using a UF-1000i analyzer as the detection device. The differences between pregnant women and non-pregnant women in terms of the aforementioned parameters as well as the differences of such parameters in different trimesters of pregnancy were clarified. The experimental subjects were divided into two groups: the experiment group (612 healthy pregnant women) and the control group (582 healthy non-pregnant women). Subjects of both groups are women between the age of 22 and 46. The urine specimens were analyzed using the Sysmex UF-1000i analyzer, followed by manual correction. A statistical analysis was performed by SPSS 22.0. Results were considered significant at p < 0.01. The pregnancy reference intervals of WBC, RBC, BACT, EC, SRC, and MUS were 0 ~ 30/µL, 0 ~ 23/µL, 0 ~ 698/µL, 0 ~ 28/µL, 0 ~ 8/µL, and 0 ~ 3/µL, respectively. In the experiment group, the concentrations of WBC, BACT, EC, and SRC were significantly higher than those of the control group (p < 0.01), while the concentrations of RBC and MUS were significantly lower than those of the control group (p < 0.01). The inter-trimester differences in terms of the concentrations of WBC, BACT, EC, and SRC were statistically indistinguishable (p > 0.05). However, the concentration of RBC was significantly lower with the increase of trimester of pregnancy (the comparison between the first trimester with the second trimester: p = 0.000 < 0.01; the comparison between the second trimester and the third trimester: p = 0.004 < 0.01). The WBC, BACT, EC, and SRC had moderate intercorrelations (0.569 ~ 0.681, p < 0.01). There were significant differences in the aforementioned parameters between the two groups. The intervals of WBC, RBC, BACT, EC, SRC, and MUS for urine sediment analysis of healthy pregnant women using a UF-1000i should be established.


Strain-based estimation of time-dependent transmural myocardial architecture in the ovine heart.
Left ventricular myofibers are connected by an extensive extracellular collagen matrix to form myolaminar sheets. Histological cardiac tissue studies have previously observed a pleated transmural distribution of sheets in the ovine heart, alternating sign of the sheet angle from epicardium to endocardium. The present study investigated temporal variations in myocardial fiber and sheet architecture during the cardiac cycle. End-diastolic histological measurements made at subepicardium, midwall, and subendocardium at an anterior-basal and a lateral-equatorial region of the ovine heart, combined with transmural myocardial Lagrangian strains, showed that the sheet angle but not the fiber angle varied temporally throughout the cardiac cycle. The magnitude of the sheet angle decreased during systole at all transmural depths at the anterior-basal site and at midwall and subendocardium depths at the lateral-equatorial site, making the sheets more parallel to the radial axis. These results support a previously suggested accordion-like wall-thickening mechanism of the myocardial sheets.


Effects of vasoactive agonists on the membrane potential of cultured bovine aortic and guinea-pig coronary endothelium.
1. The effects of bradykinin, ATP, adenosine, histamine and thrombin on the membrane potential of confluent monolayers of cultured bovine aortic endothelial cells (BAECs) and guinea-pig coronary endothelial cells (GCECs) were studied at 37 degrees C using the whole-cell mode of the patch-clamp technique. 2. The amplitude histogram of the resting potentials of BAEC monolayers showed a bimodal distribution with one peak around -25 mV and another peak around -85 mV. Transitions from one potential level to the other were observed. The bistable membrane potential can be explained by an N-shaped current-voltage relation of the endothelial cell membrane. 3. When BAECs with a low resting potential (-10 to -30 mV) were superfused with maximally effective concentrations of ATP (2-10 microM) an initial hyperpolarization of -80 to -90 mV was observed which decayed to a plateau of about -60 mV within 1 min. When ATP was removed after 2-3 min the membrane potential returned to control level within 1 min. This was followed by a second hyperpolarization of 10-20 mV, which decayed within 15 min. 4. In the absence of extracellular calcium, ATP produced only a brief transient hyperpolarization in aortic endothelium. The plateau and the secondary hyperpolarization were abolished. These findings are consistent with the idea that the changes in membrane potential reflect changes in intracellular free Ca2+ and that the initial peak is due to release of Ca2+ from intracellular stores, whereas the plateau and the secondary hyperpolarization depend on transmembrane Ca2+ influx. 5. Bradykinin evoked potential changes similar to ATP in BAECs, except that the secondary hyperpolarization during wash-out was absent. When the membrane potential was more negative than -80 mV, ATP and bradykinin induced only a small initial hyperpolarization followed by a depolarization of up to 20 mV. 6. In aortic endothelium, ADP (10 microM) evoked a much smaller response than ATP. Adenosine (10 microM), thrombin (2 units/ml), acetylcholine (10 microM) and histamine (10 microM) had only a very small effect on the membrane potential, if any. 7. The amplitude histogram of the membrane potential of GCECs showed only one peak around -35 mV. In coronary endothelium, application of bradykinin, ATP, histamine, thrombin, acetylcholine and adenosine all evoked a transient hyperpolarization of 10-40 mV lasting 1 min or less, which then turned into a depolarization. 8. The K+ channel openers cromakalim (BRL 34915) and lemakalim (BRL 38227) did not affect the membrane potential of GCECs or BAECs.(ABSTRACT TRUNCATED AT 400 WORDS)


Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning.
Zebrafish you-too (yot) mutations interfere with Hedgehog (Hh) signaling during embryogenesis. Using a comparative synteny approach, we isolated yot as a zinc finger transcription factor homologous to the Hh target gli2. Two alleles of yot contain nonsense mutations resulting in carboxy-terminally truncated proteins. In addition to causing defects in midline development, muscle differentiation, and retinal axon guidance, yot mutations disrupt anterior pituitary and ventral forebrain differentiation. yot mutations also cause ectopic lens formation in the ventral diencephalon. These findings reveal that truncated zebrafish Gli2 proteins interfere with Hh signaling necessary for differentiation and axon guidance in the ventral forebrain.


Ultrasound assessment and conservative management of inversion injuries of the ankle in children: plaster of Paris versus Tubigrip.
We studied 45 children who presented with an inversion injury of the ankle. The clinical signs suggested injury to the distal growth plate of the fibula, but the plain radiographs appeared normal. Ultrasound examination of the joint in 40 patients showed a subperiosteal haematoma consistent with a growth-plate injury in 23 (57.5%). Children who had been treated with a tubular bandage and crutches by random selection had a mean time to return of normal activity of 14.22 days compared with 21.60 days for those treated with a plaster-of-Paris cast (t=3.60, p=0.0032; d=7.38, 95% CI 3.0 to 11.8). We conclude that children with inversion ankle injuries who have clinical signs of injury to the distal fibular growth plate but a normal radiological appearance, should be treated with a tubular bandage and crutches.