A comparison of traditional plant knowledge between Daman people and Tibetans in Gyirong River Valley, Tibet, China.
By comparing the differences in plant use between various cultures or regions, we can gain a better understanding of traditional knowledge of plant use among different groups, which may lead to a more objective understanding. Even though the Tibetan and Daman people live in the same ecosystem in Gyirong town, China, their cultural backgrounds and livelihoods differ. Therefore, the objective of this study is to document the traditional knowledge of plant use among the Daman people and compare it with the local Tibetan knowledge of plant use. By doing so, we aim to explore the relationship between plant selection and use and the cultural backgrounds of different groups. During fieldwork, ethnobotanical data were collected using various methods including free listings, key informant interviews, and semi-structured interviews. To quantify the importance of plant species in the Daman people's culture, the culture importance index, informant consensus factor index, and The Index of Agreement on Species consensus (IASc) were used. In addition, we cited previous ethnobotanical survey data from the Tibetan in Gyirong. To more comprehensively compare the differences in plant use between the Daman and Tibetan, this study constructed a knowledge network to compare the knowledge differences between the two groups. In this study, traditional knowledge was collected from 32 Daman informants, resulting in a total of 68 species belonging to 39 families mentioned by Daman people and 111 species mentioned by Tibetans. Of these, 58 plants were used by both populations. The plants were classified into 3 categories and 28 subcategories, with 22 identical classes in both groups. The majority of use categories showed a high degree of sharing in both groups, and the Tibetan people had more plant use categories than the Daman people. Five plants with IASc value > 0.5 were identified in both groups: Rhododendron anthopogon D. Don, Artemisia japonica Thunb., Juniperus indica Bertol., Gastrodia elata Blume, and Rheum australe D. Don. The analysis of the knowledge network revealed a 66% overlap between the knowledge of the Daman and the knowledge of the Tibetans. Additionally, the plant knowledge of Tibetan people was found to be richer and more complex than that of the Daman people. However, the Daman people possess 30 unique knowledge items. From the perspective of plant use, the history of the Daman people's discrete migration on the border between China and Nepal allows them to retain their own knowledge of plant use. The status quo of joining Chinese nationality and settling in Gyirong town allows them to gradually integrate into the local Tibetan society. In summary, despite living in the same ecosystem and biodiversity background, the plant utilization of the Daman people and Tibetans still shows significant differences, which are due to their different cultural backgrounds and social status.


Mineral trioxide aggregate as a pulpotomy medicament: a narrative review.
Several medicaments have been used to devitalize remaining pulp or maintain pulp vitality and promote healing. Based on pulpal biocompatibility and good sealing ability, a growing interest in more biocompatible materials promotes mineral trioxide aggregate (MTA) as an alternative to traditional medicaments. Uniquely, MTA can preserve pulpal health predictably and promote healing with pulp regeneration. Using electronic search all papers published since 1993 on the use of MTA in paediatric dentistry were identified. This paper provides a narrative review of the current literature on MTA, formocresol, ferric sulphate and calcium hydroxide with particular reference to primary teeth pulpotomy medication. The use of formocresol or formaldehyde-based medicaments should be replaced with more biocompatible medicaments possessing antimicrobial and pulpal regenerative properties. Of the four pulpotomy medicaments discussed, mineral trioxide aggregate is recommended as the medicament of choice.


Cervical Benign Teratoma: Case Report and Review of Literature.
Cervical teratomas are extremely rare germ cell tumours and it is much more common in newborn than adults, and in contrast to the paediatric cases adult teratomas have been highly malignant. Cervical teratoma incorporates lesions arising in the anterior and posterior triangles of the neck. This tumor can reach enormous size and cause airway obstruction and patients should be quickly treated. Surgery is the primary modality of treatment as malignant transformation can occur. Hereby, we present a case of benign teratoma of neck in adult which was completely misdiagnosed preoperatively due to its rare occurrence in adults.Even though cervical teratoma of adult is extremely rare, it should be considered as an important differential diagnosis in patient of midline cystic neck swelling. Preoperative radiological investigations requires high index of suspicion. Complete surgical resection is recommended. We believe that upper cervicotomy approach is a safe and effective method for the treatment of mature cervical teratoma with a few protruding into the superior mediastinum. The online version contains supplementary material available at 10.1007/s12070-023-03748-8.


[¹²³I]Iodometomidate imaging in adrenocortical carcinoma.
Imaging with [¹²³I]iodometomidate ([¹²³I]IMTO) has been shown to diagnose adrenocortical lesions with high sensitivity and specificity. Our objective was to evaluate the clinical utility of [¹²³I]IMTO imaging in adrenocortical carcinoma (ACC). We conducted a prospective monocentric diagnostic study and a prospective case series at a single tertiary referral center. Fifty-eight patients with histologically confirmed ACC, all European Network for the Study of Adrenal Tumors stage IV (with distant metastases), received 185 MBq [¹²³I]IMTO. Sequential planar whole-body scans until 24 hours post injection and single photon emission computed tomography/computed tomography (SPECT/CT) hybrid imaging 4 to 6 hours post injection were performed. Outcome measures included uptake of [¹²³I]IMTO in ACC lesions, sensitivity and specificity of [¹²³I]IMTO imaging compared with conventional imaging, and number of patients eligible for [¹³¹I]IMTO therapy. Of 430 lesions detected by conventional imaging, 30% showed strong, 8% moderate, and 62% no tracer accumulation. [¹²³I]IMTO detected both primary and metastatic lesions of ACC. However, a substantial percentage of lesions failed to show [¹²³I]IMTO uptake. The overall sensitivity and specificity values were 38% and 100%, respectively. Thirty-four patients (59%) had at least 1 [¹²³I]IMTO-positive lesion. Cortisol and aldosterone secretion by ACC was positively correlated to [¹²³I]IMTO uptake (P = .01); cytotoxic chemotherapy and mitotane treatment presumably did not influence tracer uptake. Twenty-one patients (36.2%) had radiotracer uptake in all lesions ≥ 2 cm and therefore were potential candidates for targeted systemic radiotherapy with [¹³¹I]IMTO. About one-third of patients with ACC show specific retention of [¹²³I]IMTO in metastatic lesions. This study provides support for the conduct of a prospective trial to determine whether the first molecular informed therapy using [¹³¹I]IMTO will be of value to patients with metastatic ACC.


Inducing chimeric antigen receptor (CAR) regulatory T cells in-vivo: A novel concept for a potential feasible cure of demyelinating diseases.
Chimeric antigen receptor (CAR) regulatory T cell (Treg) therapy has approved promising in murine experiments. It comprises from ex-vivo introduction of CARs to the Tregs of the recipient, and infusing them back thereafter. This process requires enormous amounts of equipment and expertise and therefore, cannot be considered feasible for people with demyelinating diseases, even if it proves to be effective and safe in the future. The presented novel concept introduces feasibility to CAR Treg therapy, by shifting most of the ex-vivo processes in-vivo. Inter-disciplinary discussions on such concepts is encouraged among experts in different fields.


Pathological Internet Use Is on the Rise Among European Adolescents.
Increased Internet accessibility has been accompanied by an increased awareness of pathological Internet use (PIU). The aim of the study was to investigate a potential increase of PIU among European adolescents. Comparable data from two large cross-sectional multicentre, school-based studies conducted in 2009/2010 and 2011/2012 in five European countries (Estonia, Germany, Italy, Romania, and Spain) were used. The Young's Diagnostic Questionnaire was used to assess the prevalence of PIU. The comparison of the two samples provides evidence that the prevalence of PIU is on the rise (4.01%-6.87%, odds ratio = 1.69, p < .001) except in Germany. Comparison with data on Internet accessibility suggests that the rise in prevalence of adolescent PIU may be a consequence of increased Internet accessibility. Our findings are the first data to confirm the rise of PIU among European adolescents. They definitively warrant further efforts in the implementation and evaluation of preventive interventions.


Parapharyngeal lipoma extending to skull base: a case report and review of the literature.
Lipomas in the head and neck region usually occur in the immediate subcutaneous tissue. They are extremely rare in the parapharyngeal space. A rare case of a right parapharyngeal space lipoma extending to skull base in an 18-year-old male is reported. The literature is reviewed and the characteristics of disease are discussed.


[Diagnostic and therapeutic management of acute abdomen in Hajah, Yemen].
We report on the results of surgical treatment in 236 patients admitted with clinical signs of acute abdomen between the 1st of January 2000 and the 31st of December 2003 at the District Hospital of Hajah in northwest Yemen. Hajah, a city 2500 m above sea level, has 60,000 inhabitants and serves an area with 800,000 inhabitants. The hospital was funded by the Saudi Arabian government and built in 1997. Data on patients with acute abdominal pain were prospectively collected and analysed according to diagnosis, age, sex, and duration of symptoms. The most frequent cause was acute appendicitis, followed by incarcerated inguinal hernia. Complicated ulcer diseases of the upper gastrointestinal tract and gynaecological disorders were also frequently diagnosed. Gunshot wounds were the most frequent trauma. Despite the limited diagnostic equipment at the Hajah District Hospital and the short duration of hospital stay, there was no fatal event during the 1-year period analysed. The management of patients with acute abdominal pain and the ability to arrive at exact diagnosis is dependent on the availability of diagnostic means such as abdominal ultrasound and CT scan. However, especially in rural countries with only rudimentary technology, far more depends on the professional training and qualification of the surgeons responsible.


Gangliosides stimulate synthesis of prostaglandin E2 and prostacyclin in fetal rat brain hemispheres after episodes of global intrauterine ischemia.
The ability of brain preparations from 20-day-old rat fetuses to synthesize prostanoids in vitro before and after interruption of the maternal-fetal blood flow was examined using a radioimmunoassay technique. Synthesis of thromboxane B2 (TxB; the stable thromboxane A2 metabolite) decreased with increasing restriction time; conversely, it was elevated with reperfusion. Synthesis of 6-keto prostaglandin F1 alpha (PGF; the stable prostacyclin metabolite) and prostaglandin E2 (PGE) prostanoids remained unchanged after 20 min restriction and through a 2 hr reperfusion period. Intraperitoneal administration of GM1 (45 mg/kg) into the pregnant rat, 3 hr before restriction, stimulated synthesis of PGE and reduced synthesis of TxB. A prostanoid vasoactive index (PVI), which reflects the relative proportion of the three prostanoids synthesized and asserts the vasoactive potential of the brain tissue, was established. A rise in this value was attained after intrafetal administration into the peritoneal cavity of either GM1, GM3, or isopropyl-GM1 (AGF44) gangliosides, each given at 40 micrograms dose in 5 microliters volume, and N-dichloroacetyl-sphingosine (LIGA20; 15 micrograms/5 microliters) ganglioside analog, 1 hr before restriction. The effect was primarily due to an increase in the capacity of fetal brain tissue to synthesize PGE and, to a lesser extent PGF, vasodilating prostanoids. The N-methyl-D-aspartate (NMDA) receptor-blocker MK801 (6.6 micrograms/2 microliters) and the platelet activating factor (PAF) receptor antagonist BN52021 (0.1 mumol/2 microliters), given by the same route, effectively raised by 60-80% the vasodilating potential of the brain tissue following ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


CD317 mediates immunocytolysis resistance by RICH2/cytoskeleton-dependent membrane protection.
Immune evasion is a common hallmark of cancers. Immunotherapies that aim at restoring or increasing the immune response against cancers have revolutionized outcomes for patients, but the mechanisms of resistance remain poorly defined. Here, we report that CD317, a surface molecule with a unique topology that is double anchored into the membrane, protects tumor cells from immunocytolysis. CD317 knockdown in tumor cells renders more severe death in response to NK or chimeric antigen receptor-modified NK cells challenge. Such effects of CD317 silencing might be the results of increasing sensitivity of tumor cells to immune killing rather than strengthening immune response, since neither effector-target cell contact nor the activation of effector cells was affected, and the enhanced cytolysis was also not counteracted by the addition of recombinant CD317 proteins. Mechanistically, CD317 might endow tumor cells with more flexibility to modulate cytoskeleton through its association with RICH2, thereby protects membrane integrity against perforin and consequently promotes survival in response to immunocytolysis. These results reveal a new mechanism of immunocytolysis resistance and suggest CD317 as an attractive target which can be exploited for improving the efficacy of cancer immunotherapies.


Alterations of the oxidative status in rat hippocampus and prodepressant effect of chronic testosterone enanthate administration.
In a last few decades, anabolic-androgenic steroids (AASs) abuse has become serious health concern especially among adolescents. AASs abuse has been reported to be involved in pathogenesis of various mood disorders, including depression. In order to evaluate the effects of chronic (6 weeks) testosterone enanthate (TE) treatment in supraphysiological dose and exercise on depression-like behavior in rats, 32 male rats were divided into four groups: control (C), testosterone enanthate (T, 20 mg/kg/w, s.c.), exercise (E, swimming for 1 h/day), and combined group-testosterone enanthate plus exercise (T + E). TE produced prodepressant effect in tail suspension test (TST) parameters compared to the control and exercise groups, while exercise induced the opposite effect. Simultaneous TE administration along with exercise attenuated the antidepressant effect of exercise reversing the parameters of TST to the control values. Oxidative stress markers in rat hippocampus were significantly altered following applied protocols. TE administration increased index of lipid peroxidation (TBARS) and decreased superoxide dismutase activity (SOD), while exercise induced the opposite effect, with no change in glutathione (GSH) levels. Our results indicate that TE chronic treatment resulted in clear depressive-like behavior, even abolishing beneficial antidepressant effects of exercise in TST that was accompanied with increased oxidative damage in rat hippocampus. The antidepressant effect of exercise correlated with the improvement of redox status in hippocampal tissue. Behavioral parameters obtained in TST significantly correlated with the levels of oxidative stress markers.


The ETS transcription factor ELF1 regulates a broadly antiviral program distinct from the type I interferon response.
Induction of vast transcriptional programs is a central event of innate host responses to viral infections. Here we report a transcriptional program with potent antiviral activity, driven by E74-like ETS transcription factor 1 (ELF1). Using microscopy to quantify viral infection over time, we found that ELF1 inhibits eight diverse RNA and DNA viruses after multi-cycle replication. Elf1 deficiency results in enhanced susceptibility to influenza A virus infections in mice. ELF1 does not feed-forward to induce interferons, and ELF1's antiviral effect is not abolished by the absence of STAT1 or by inhibition of JAK phosphorylation. Accordingly, comparative expression analyses by RNA-seq revealed that the ELF1 transcriptional program is distinct from interferon signatures. Thus, ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.


Improving functionality, bioavailability, nutraceutical and sensory attributes of fortified foods using phenolics-loaded nanocarriers as natural ingredients.
The replacement of artificial by natural additives has gained consumer attention due to concerns about toxic and carcinogenic effects of artificial additives and the growing search for healthy foods. Phenolics are considered as one of the most important natural ingredients in the human diet due to the unique antimicrobial and antioxidant properties. However, the use of phenolics is limited by its poor solubility, undesirable sensorial properties and instability during food processing and storage. To overcome these challenges and to improve the functionality and bioavailability of phenolics, many studies have attempted to encapsulation of phenolics using delivery systems. This review summarizes the recent advances in application of encapsulated phenolics as a natural additive in different food products as well as their effects on functionality and sensory quality. Finally, we have highlighted the key research gaps and future trends in the research domain of application of encapsulated phenolics in foodstuffs. In the literature several studies on physicochemical properties of encapsulated phenolics with different biopolymers and delivery systems were evaluated and based on the results, their applications in various food formulations were suggested for further studies. This review revealed encapsulation techniques especially nanoencapsulation improves the half-stability and functionality of phenolics in fortified food.


Physiologically Based Pharmacokinetic Modeling for Multiple Oral Administration Labetalol in Pregnant Women.
Labetalol has an irreplaceable role in treating Hypertensive disorders of pregnancy (HDP), a common disease during pregnancy with a prevalence of 5.2-8.2%. However, there were big differences in dosage regimens between various guidelines. A physiologically-based pharmacokinetics (PBPK) model was established and validated to evaluate the existing oral dosage regimens, and to compare the difference in plasma concentration between pregnant and non-pregnant women. First, non-pregnant woman models with specific plasma clearance or enzymatic metabolism (UGT1A1, UGT2B7, CYP2C19) were established and validated. For CYP2C19, slow, intermediate, and rapid metabolic phenotypes were considered. Then, a pregnant model with proper structure and parameters adjustment was established and validated against the multiple oral administration data. The predicted labetalol exposure captured the experimental data well. The following simulations with criteria lowering 15 mmHg blood pressure (corresponding to around 108 ng/ml plasma labetalol) found that the maximum daily dosage in the Chinese guideline may be insufficient for some severe HDP patients. Moreover, similar predicted steady-state trough plasma concentration was found between the maximum daily dosage in the American College of Obstetricians and Gynecologists (ACOG) guideline, 800 mg Q8h and a regimen of 200 mg Q6h. Simulations comparing non-pregnant and pregnant women found that the difference in labetalol exposure highly depended on the CYP2C19 metabolic phenotype. In summary, this work initially established a PBPK model for multiple oral administration of labetalol for pregnant women. This PBPK model may lead to personalized labetalol medication in the future.


Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice.
Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid peroxidation as evident by increased in reactive oxygen species, nitric oxide level, and malondialdehyde (MDA) formation with decreased in level of antioxidants such as reduced glutathione, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. Furthermore, CP at a dose of 25 mg/kg b.w. increased pulmonary DNA damage ('comet tail') and triggered DNA fragmentation and apoptosis in mouse bone marrow cells. On the other hand, Nano-Se at a dose of 2 mg Se/kg b.w., significantly inhibited CP-induced DNA damage in bronchoalveolar lavage cells, and decreased the apoptosis and percentage of DNA fragmentation in bone marrow cells and also antagonized the reduction of the activities of antioxidant enzymes and the increase level of MDA. Thus, our results suggest that Nano-Se in pre- and co-administration may serve as a promising preventive strategy against CP-induced pulmonary toxicity.


Paclitaxel-Eluting versus Everolimus-Eluting Coronary Stents in Diabetes.
The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents. We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up. At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002). In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. (Funded by Boston Scientific; TUXEDO-India Clinical Trials Registry-India number, CTRI/2011/06/001830).


Long-term follow-up of pregnant women after percutaneous mitral valvuloplasty.
The aim of this study was to evaluate long-term clinical follow-up and echocardiographic data on pregnant patients with mitral stenosis who underwent percutaneous mitral valvuloplasty (PMV) in our center and the development of their infants. PMV has proven to be an effective alternative to treat pregnant patients with mitral stenosis. However, long-term outcome of these patients, as well as the potential harmful effects caused by radiation on their infants, still awaits to be determined. From January 1988 to February 1999, 30 pregnant women (mean gestational duration, 24.95 +/- 5.59 weeks) underwent PMV. Twenty-three (77%) were subsequently followed by a medical interview during 5.33 +/- 3.12 years. Clinical variables such as NYHA functional class (FC), the need of a repeat PMV or surgical procedure, the presence of embolic events, and mortality rate were evaluated during follow-up. Mitral valve area, mean transmitral gradient, and the presence of mitral regurgitation were also assessed by Doppler echocardiography. Clinical data on the development of the infants were obtained from the assistant pediatricians. All patients were in NYHA FC III or IV before the procedure. During follow-up, 91% of them were in FC I and II. Two patients (9%) who had remained in FC III underwent a repeat successful PMV; no further surgery was required. There were no embolic events or death related to the procedure. Echocardiography showed an initial increase in mitral valve area from 1.14 +/- 0.22 cm(2) to 2.01 +/- 0.21 cm+/- (P < 0.0001). During long-term follow-up, it decreased to a mean of 1.75 +/- 0.24 cm(2) (P < 0. 0001). Initial transmitral valve gradient decreased from 17.73 +/- 4. 56 mm Hg to 5.91 +/- 1.80 mm Hg (P = 0.0001) and 8.95 +/- 3.58 (P = 0.002) during long-term follow-up. Twenty one children (96%), aged 4. 91 +/- 2.8 years, showed normal growth and development, and no clinical abnormalities were observed. These favorable long-term results suggests PVM to be the procedure of choice to treat pregnant women with mitral stenosis who remain in FC III or IV despite adequate medical therapy. No harmful effects due to the use of radiation were observed in the children.


Hepatocyte transplantation as a treatment for glycogen storage disease type 1a.
Treatment of many inherited disorders of hepatic metabolism is still challenging. Hepatocyte transplantation was done in a 47-year-old woman who had glycogen storage disease type 1a and severe fasting hypoglycaemia. 2 billion viable hepatocytes were infused via an indwelling portal-vein catheter, followed by a triple immunosuppression regimen with mycophenolate mofetil, tacrolimus, and steroids. 9 months after transplantation, on only tacrolimus, she eats a normal diet and can fast for 7 h without experiencing hypoglycaemia. Our results show that hepatocyte transplantation might be an alternative to liver transplantation in glycogen storage disease type 1a.


Split-field vs extended-field intensity-modulated radiation therapy plans for oropharyngeal cancer: Which spares the larynx? Which spares the thyroid?
Radiation of the low neck can be accomplished using split-field intensity-modulated radiation therapy (sf-IMRT) or extended-field intensity-modulated radiation therapy (ef-IMRT). We evaluated the effect of these treatment choices on target coverage and thyroid and larynx doses. Using data from 14 patients with cancers of the oropharynx, we compared the following 3 strategies for radiating the low neck: (1) extended-field IMRT, (2) traditional split-field IMRT with an initial cord-junction block to 40Gy, followed by a full-cord block to 50Gy, and (3) split-field IMRT with a full-cord block to 50Gy. Patients were planned using each of these 3 techniques. To facilitate comparison, extended-field plans were normalized to deliver 50Gy to 95% of the neck volume. Target coverage was assessed using the dose to 95% of the neck volume (D95). Mean thyroid and larynx doses were computed. Extended-field IMRT was used as the reference arm; the mean larynx dose was 25.7 ± 7.4Gy, and the mean thyroid dose was 28.6 ± 2.4Gy. Split-field IMRT with 2-step blocking reduced laryngeal dose (mean larynx dose 15.2 ± 5.1Gy) at the cost of a moderate reduction in target coverage (D95 41.4 ± 14Gy) and much higher thyroid dose (mean thyroid dose 44.7 ± 3.7Gy). Split-field IMRT with initial full-cord block resulted in greater laryngeal sparing (mean larynx dose 14.2 ± 5.1Gy) and only a moderately higher thyroid dose (mean thyroid dose 31 ± 8Gy) but resulted in a significant reduction in target coverage (D95 34.4 ± 15Gy). Extended-field IMRT comprehensively covers the low neck and achieves acceptable thyroid and laryngeal sparing. Split-field IMRT with a full-cord block reduces laryngeal doses to less than 20Gy and spares the thyroid, at the cost of substantially reduced coverage of the low neck. Traditional 2-step split-field IMRT similarly reduces the laryngeal dose but also reduces low-neck coverage and delivers very high doses to the thyroid.


The Fat-like cadherin CDH-4 controls axon fasciculation, cell migration and hypodermis and pharynx development in Caenorhabditis elegans.
Cadherins are one of the major families of adhesion molecules with diverse functions during embryonic development. Fat-like cadherins form an evolutionarily conserved subgroup characterized by an unusually large number of cadherin repeats in the extracellular domain. Here we describe the role of the Fat-like cadherin CDH-4 in Caenorhabditis elegans development. Cdh-4 mutants are characterized by hypodermal defects leading to incompletely penetrant embryonic or larval lethality with variable morphogenetic defects. Independently of the morphogenetic defects cdh-4 mutant animals also exhibit fasciculation defects in the ventral and dorsal cord, the major longitudinal axon tracts, as well as migration defects of the Q neuroblasts. In addition CDH-4 is essential for establishing and maintaining the attachment between the buccal cavity and the pharynx. Cdh-4 is expressed widely in most affected cells and tissues during embryogenesis suggesting that CDH-4 functions to ensure that proper cell contacts are made and maintained during development.


Biodiversity conservation policy in megadiverse countries: Comparing policy systems for 2020 targets to inform management in the coming decades.
The year 2020 marks a crucial deadline for signatories to the Convention on Biological Diversity (CBD), the most important global agreement for biodiversity conservation, which requires nations to meet conservation targets. Managers and decision-makers need a better understanding of the policy systems established to meet conservation targets in order to inform post-2020 CBD policy implementation. This paper compares two policy systems for implementing marine protected areas (MPAs) which protect a threatened source of biodiversity, coral reefs. Comparing a centralized policy system, with power emanating from ministries (Malaysia), with a decentralized policy system, with power concentrated in subnational government (Indonesia), provides insights. Policy process literature is used to build on the already substantial interdisciplinary literature on MPAs, drawing novel insights into policy-makers and how they determine policy problems, shape policy options, and are influenced by political events. Findings are that the tropics-wide coral bleaching event in 2015-2016 fundamentally changed the way managers perceived the problems that biodiversity conservation policy solves. Managers are beginning to prioritize policy responses to climate stressors with the same urgency as historically important stressors like overfishing, implementing responses at starkly different power centers within policy systems. Non-governmental organizations (NGOs), subnational governments, and the private sector are implementing innovative policy responses in the decentralized system, while the same actors in the centralized system face constraints because of its rigid policy framework. Understanding where starkly different power centers, and related dynamism, fall within policy systems allows for more effective reforms and investments for the next iteration of the CBD.


Glomerular and serum immunoglobulin G subclasses in IgA nephropathy.
The distribution of human IgG subclasses among mesangial glomerular deposits of 11 patients with IgA nephropathy (IgA-N) was examined by indirect immunofluorescence with subclass-specific mouse monoclonal antibodies (mAb). A subclass restriction was observed with mesangial deposits containing almost exclusively IgG1 (81% of the studied biopsies) and IgG3 (64%). IgG2 was present in only 1 out of the 11 cases studied and IgG4 was never found to be present, although seven different anti-IgG4 mAb were used. In addition, serum levels of total IgA and IgG, as well as serum IgG subclass levels, were measured in 27 patients with IgA nephropathy by an indirect competitive immunoenzymatic assay using mAb. It was noted in IgA-N patients, but not in normal individuals, that there was significant positive correlation between total IgA and IgG serum levels which was entirely due to a positive correlation between total serum IgA and IgG2 levels. This study provides no explanation for the subclass restrictions observed but suggests that (i) the presence of IgA-IgG1-IgG3 in mesangial deposits may be secondary to an antigenic stimulation, possibly viral, and (ii) the positive correlation between IgA and IgG2 serum levels may result from an increased T helper function.


Incidental radiation to uninvolved internal mammary lymph nodes in breast cancer.
Routine treatment of clinically uninvolved internal mammary nodes in breast cancer patients requiring post-mastectomy radiation therapy is controversial. The purpose of this study was to measure the incidental radiation dose to the internal mammary lymph nodes not included in the planning target volume (PTV) in women with breast cancer receiving post-mastectomy radiation therapy. This retrospective protocol utilized CT-based 3D conformal treatment plans. Fifty consecutive patients were included in the analysis: 25 left breast and 25 right breast patients. 3D conformal treatment plans chest wall tangent fields and matched supraclavicular were used. All plans were prescribed to a total dose of 50 Gy in 25 fractions to the chest wall and 46 Gy in 23 fractions to the supraclavicular field. The internal mammary node chain was intentionally not included in the target volume. For purposes of this study, internal mammary vessels were contoured following the Radiation Therapy Oncologist Group atlas with a 7-mm PTV expansion, utilizing original CT simulation images. The internal mammary nodes were contoured in between the first 3 and first 5 intercostal spaces for comparison. Percent volume of internal mammary node PTV receiving 95 % of the prescribed dose (47.5 Gy) with 7-mm expansion and first 5 intercostal spaces for all patients was 25.2 % (range 0.04-97.6 %, standard deviation (SD) 23.5). The mean internal mammary node dose for all patients was 24.98 Gy (range 3.54-55.93 Gy, SD 16). Results of this study suggest the incidental dose to the internal mammary nodes does not achieve clinically significant therapeutic levels in post-mastectomy breast cancer patients treated with standard 3D conformal radiation therapy chest wall irradiation. If risk factors for microscopic involvement are present, internal mammary nodes must be specifically included in target volumes in order to be adequately treated.


Renormalized random walk study of oxygen absorption in the human lung.
The possibility to renormalize random walks is used to study numerically the oxygen diffusion and permeation in the acinus, the diffusion cell terminating the mammalian airway tree. This is done in a 3D tree structure which can be studied from its topology only. The method is applied to the human acinus real morphology as studied by Haefeli-Bleuer and Weibel in order to compute the respiratory efficiency of the human lung. It provides the first quantitative evidence of the role of diffusion screening in real 3D mammalian respiration. The net result of this study is that, at rest, the efficiency of the human acinus is only of order 33%. Application of these results to CO2 clearance provides for the first time a theoretical support to the empirical relation between the O2 and CO2 partial pressures in blood.


Small molecule recognition of c-Src via the Imatinib-binding conformation.
The cancer drug, Imatinib, is a selective Abl kinase inhibitor that does not inhibit the closely related kinase c-Src. This one drug and its ability to selectively inhibit Abl over c-Src has been a guiding principle in virtually all kinase drug discovery efforts in the last 15 years. A prominent hypothesis explaining the selectivity of Imatinib is that Abl has an intrinsic ability to adopt an inactive conformation (termed DFG-out), whereas c-Src appears to pay a high intrinsic energetic penalty for adopting this conformation, effectively excluding Imatinib from its ATP pocket. This explanation of the difference in binding affinity of Imatinib for Abl versus c-Src makes the striking prediction that it would not be possible to design an inhibitor that binds to the DFG-out conformation of c-Src with high affinity. We report the discovery of a series of such inhibitors. We use structure-activity relationships and X-ray crystallography to confirm our findings. These studies suggest that small molecules are capable of inducing the generally unfavorable DFG-out conformation in c-Src. Structural comparison between c-Src in complex with these inhibitors allows us to speculate on the differential selectivity of Imatinib for c-Src and Abl.


Very low density and low density lipoprotein subfractions in type III and type IV hyperlipoproteinemia. Chemical and physical properties.
Subfractions of CLDL (VLDL), Sf 100-400; CLDL2, Sf 60--100; VLDL3, Sf 20--60) and LDL (LDL), Sf 12--20; LDL2, Sf 6--12; LDL3, Sf 3--6) were isolated from the plasma of three normal, three type III and four type IV hyperlipoproteinemic subjects. In the type IV group, all VLDL subspecies were of normal composition but were increased in concentration in the order VLDL1 greater than VLDL2 greater than VLDL3. In the same subjects, although LDL2 was lowered and LDL3 increased, the total plasma LDL concentration was normal. All VLDL subfractions were elevated in the type III group, but in this case VLDL3 predominated. These subfractions were enriched in cholesteryl esters and depleted in triglyceride. In the LDL density range there was a shift of mass towards the least dense fraction, LDL1, which was of normal composition. EPR studies of the VLDL and LDL subfractions in a type IV subject demonstrated a decrease in fluidity with increasing density. The major change occurred between VLDL3 and LDL1 and was attributed to a substantial alteration in the cholesteryl ester : triglyceride ratio in the particle. A similar argument was used to explain thction in normal or type IV subjects. Particle diameters, determined by laser light-scattering spectroscopy were in good agreement with the values obtained by electron microscopy. This study provides a baseline for the examination of the relationship between the physical and metabolic properties of VLDL and LDL subfractions in type III and IV hyperlipoproteinemia.


Identification of prognostic melatonin-related lncRNA signature in tumor immune microenvironment and drug resistance for breast cancer.
Melatonin is a neurohormone involved in diverse physiological processes, including regulation of circadian rhythm, oncogenesis and immune function. More attention are focused on the molecular events surrounding the occurrence of abnormally expressed lncRNAs leading to breast cancer. The purpose of this study was to evaluate the role of melatonin-related lncRNAs in the clinical management of BRCA patients and their immune responses. The transcriptome data and clinical data of BRCA patients were acquired from TCGA database. A total of 1103 patients were randomly assigned to either training set or validation set. A melatonin-related lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis, immune microenvironment and drug resistance analysis associated to melatonin-related lncRNAs were performed by utilizing GO&KEGG, ESTIMATE and TIDE analysis. A nomogram based on the signature score and clinical characteristics was established, which was calibrated to increase prediction probability of 1-year, 3-year and 5-year survival for BRCA patients. BRCA patients were divided into two signature groups based on a 17-melatonin-related lncRNA signature. High-signature patients had worse prognosis than low-signature patients (p < 0.001). Univariate and multivariate Cox regression analysis proved that the signature score was an independent prognostic factor for BRCA patients. Functional analysis indicated that high-signature BRCA involved in regulation of processing and maturation of mRNA and misfolded protein response. Remarkably, immune microenvironment analysis showed that the proportion of tumor-infiltrating M2 macrophage and the expression of CTLA4 were significantly higher in high-signature BRCA. The calibration curves for the probability of invasive BRCA showed optimal agreement between the probability as predicted by the nomogram and the actual probability. A novel melatonin-related lncRNA signature was considered as an independent prognostic indicator for BRCA patients. Melatonin-related lncRNAs were potentially associated with tumor immune microenvironment and might be therapeutic targets for BRCA patients.


2-Bromo-4-(3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-yl)-6-meth-oxy-phenol.
In the title compound, C(18)H(20)BrNO(3), the oxazolidine ring adopts an envelope conformation with the N atom at the flap position. The mean plane of oxazolidine ring makes dihedral angles of 82.96 (13) and 70.97 (12)°, respectively, with the phenyl and benzene rings. In the crystal, adjacent mol-ecules are connected via O-H⋯O and C-H⋯O hydrogen bonds and C-H⋯π inter-actions into a zigzag chain along the b axis.


Radionuclide diagnosis of venous angioma.
Venous angioma is a rare vascular anomaly of the central nervous system. Pathologically, it resembles arteriovenous malformation, but the vascular changes are seen only in the veins. In the present case, the lesion was seen better with dynamic rather than static radionuclide examination. In a computerized dynamic study, the circulation time in the lesion was significantly prolonged compared with the circulation time in the symmetrical area of the contralateral hemisphere. The peak of the time-activity curve also appeared later in the lesion area than in the symmetrical contralateral area. Thus the use of the computerized gamma camera is useful in the diagnosis of venous angioma and the method seems to have some differential diagnostic possibilities.


Water beetle tolerance to salinity and anionic composition and its relationship to habitat occupancy.
Water salinity and ionic composition are among the main environmental variables that constrain the fundamental niches of aquatic species, and accordingly, physiological tolerance to these factors constitutes a crucial part of the evolution, ecology, and biogeography of these organisms. The present study experimentally estimated the fundamental saline and anionic niches of adults of two pairs of congeneric saline beetle species that differ in habitat preference (lotic and lentic) in order to test the habitat constraint hypothesis. Osmotic and anionic realised niches were also estimated based on the field occurrences of adult beetle species using Outlying Mean Index analysis and their relationship with experimental tolerances. In the laboratory, all of the studied species showed a threshold response to increased salinity, displaying high survival times when exposed to low and intermediate conductivity levels. These results suggest that these species are not strictly halophilic, but that they are able to regulate both hyperosmotically and hypoosmotically. Anionic water composition had a significant effect on salinity tolerance at conductivity levels near their upper tolerance limits, with decreased species survival at elevated sulphate concentrations. Species occupying lentic habitats demonstrated higher salinity tolerance than their lotic congeners in agreement with the habitat constraint hypothesis. As expected, realised salinity niches were narrower than fundamental niches and corresponded to conditions near the upper tolerance limits of the species. These species are uncommon on freshwater-low conductivity habitats despite the fact that these conditions might be physiologically suitable for the adult life stage. Other factors, such as biotic interactions, could prevent their establishment at low salinities. Differences in the realised anionic niches of congeneric species could be partially explained by the varying habitat availability in the study area. Combining the experimental estimation of fundamental niches with realised field data niche estimates is a powerful method for understanding the main factors constraining species' distribution at multiple scales, which is a key issue when predicting species' ability to cope with global change.


Time-resolved MR angiography of the thorax.
Time-resolved magnetic resonance angiography (TR-MRA) has received considerable attention recently owing to its ability to provide a dynamic complement to otherwise "static" high-resolution 3-D contrast-enhanced MRA for a variety of clinical indications. Steady technologic advances, including ultrafast pulse sequences, phased multiarray surface coils, parallel data acquisition techniques, and the widespread availability of high-field magnetic resonance systems, have enhanced the clinical usefulness of TR-MRA. This article considers the current role of TR-MRA in thoracic imaging, illustrating many of its clinical applications, and potential future of this recent approach to noninvasive dynamic vascular evaluation.


Global protein quantification of mouse heart tissue based on the SILAC mouse.
Metabolic labeling of living organisms with stable isotopes has become a powerful tool for global protein quantitation. The SILAC (stable isotope labeling with amino acids in cell culture) approach is based on the incorporation of nonradioactive-labeled isotopic forms of amino acids into cellular proteins. The effective SILAC labeling of immortalized cells and single-cell organisms (e.g., yeast and bacteria) was recently extended to more complex organisms, including worms, flies, and even rodents. The administration of a (13)C6-lysine (heavy) containing diet for one mouse generation leads to a complete exchange of the natural (light) isotope (12)C6-lysine. SILAC-labeled organisms are mainly used as a heavy "spike-in" standard into nonlabeled counterparts, and the combination with high-performance mass spectrometers allows for global proteomic screening. Here we used the fully labeled SILAC mice to identify proteins based on SILAC pairs from isolated cardiomyocytes, and we analyzed β-parvin-deficient hearts. Our approach confirmed the absence β-parvin and revealed simultaneously a clear up regulation of α-parvin in heart tissue. In this protocol, we describe the generation of a SILAC mouse colony and show two approaches to perform a proteome-wide analysis of heart tissue. Thus, the SILAC mouse spike-in approach is a readily available procedure and allows for a straightforward systematic analysis of disease models and knockout mice.


Loss of alleles on chromosome 18 and on the short arm of chromosome 17 in polyploid colorectal carcinomas.
The zygosity of 19 colorectal carcinomas (either near-diploid or polyploid) from patients known to be heterozygous for RFLPs located on chromosome 18 or on the short arm of chromosome 17 has been examined. In most cases, at least one allele was significantly under-represented. The reason for the absence of complete loss of heterozygosity was investigated for 5 polyploid tumors. It was shown that the diploid component which, in these tumors, is essentially composed of non-neoplastic cells, remains heterozygous as the polyploid component invariably loses heterozygosity. The results strongly suggest that many colorectal carcinomas originate from a single cell which had lost at least part of either chromosome 18 or of one short arm of chromosome 17, or both.


The efficacy, safety, and outcomes of testosterone use among transgender men patients: A review of the literature.
Gender dysphoria is the discrepancy between biological sex and gender identity. This can be debilitating for transgender populations, including transgender men (TM), individuals who were assigned female at birth but who identify as men, that can benefit from hormonal therapy with testosterone products to address gender dysphoria. We aim to summarize the efficacy, safety profile, and outcomes of the different testosterone replacement treatment (TRT) in the TM population. A search of the published literature regarding the various FDA-approved TRT was performed in PubMed, Web of Science and Cochrane Library from 2007 to date. We complied two groups of TRT based on route of administration including the conventional testosterone therapies (intramuscular and subcutaneous injectables, and transdermal gels) and newer testosterone therapies (oral, buccal, and nasal gels). For the conventional testosterone therapies, we identified nine studies discussed conventional TRT in TM population including one randomized trial, four prospective studies, one retrospective study and three reviews. For newer testosterone therapies, we identified three studies discussed newer TRT in TM population including one prospective study and two reviews. Articles were then compiled and analyzed. Albeit majority of TRT data stemming from conventional TRT, there appear to be an overwhelmingly safety and efficacy profile in TM population translated with increased free testosterone levels comparable to male range, menses cessation, anxiety/depression decline and improved quality of life. Testosterone therapy can be impactful for TM population with improved safety, efficiency, quality of life and function. With the rise of the newer FDA-approved TRT, randomized studies are warranted to determine its safety and efficacity in this TM population.


Prevalence and molecular characterization of Giardia duodenalis and Cryptosporidium spp. in dairy cattle in Ontario, Canada.
Giardia duodenalis and Cryptosporidium spp. are intestinal protozoan parasites that infect a wide range of host species, including humans. Molecular characterization of these parasites has demonstrated that a number of genotypes and species are common to both humans and animals, and that zoonotic transmission may occur. Numerous studies have reported a high prevalence of G. duodenalis and Cryptosporidium spp. in cattle, particularly calves, and these animals are frequently associated with zoonotic transmission. In the present study, a total of 143 faecal samples from adults, heifers and calves were collected from two dairy cattle farms in eastern Ontario, Canada. The prevalence and molecular characteristics of G. duodenalis and Cryptosporidium spp. in these animals were determined in order to investigate the potential for transmission between cattle and humans in this region. Following DNA extractions from faecal samples, nested-PCR protocols were used to amplify fragments of the 16S rRNA gene and the heat-shock protein 70 (HSP-70) gene for determining the prevalence of G. duodenalis and Cryptosporidium spp. infections, respectively. Genotypes of G. duodenalis, and species of Cryptosporidium, were determined by means of DNA sequencing of amplicons, and subsequent sequence alignment. Cattle on both farms showed a high prevalence of G. duodenalis (42.0%) and Cryptosporidium spp. (27.3%). G. duodenalis infections were more prevalent in calves and heifers than in adults, and Cryptosporidium spp. infections were only observed in calves and heifers. The zoonotic genotype, G. duodenalis Assemblage B was isolated from 24.5% of the cattle tested, while G. duodenalis Assemblage E was found in 17.5% of the cattle tested. The overall prevalence of the zoonotic species Cryptosporidium parvum in the animals tested was found to be 21.7%, while only 1.4% were infected with C. bovis. These findings suggest that there is a potential risk of zoonotic and/or zooanthroponotic transmission of G. duodenalis and C. parvum infections between cattle and humans in eastern Ontario, likely by means of contaminated water or food, or through direct faecal-oral transmission in the case of farmers and veterinary staff.


Cavitation Erosion of Cermet-Coated Aluminium Bronzes.
The cavitation erosion resistance of CuAl10Ni5Fe2.5Mn1 following plasma spraying with Al₂O₃·30(Ni20Al) powder and laser re-melting was analyzed in view of possible improvements of the lifetime of components used in hydraulic environments. The cavitation erosion resistance was substantially improved compared with the one of the base material. The thickness of the re-melted layer was in the range of several hundred micrometers, with a surface microhardness increasing from 250 to 420 HV 0.2. Compositional, structural, and microstructural explorations showed that the microstructure of the re-melted and homogenized layer, consisting of a cubic Al₂O₃ matrix with dispersed Ni-based solid solution is associated with the hardness increase and consequently with the improvement of the cavitation erosion resistance.


Lipoprotein Extraction from Microbial Membrane and Lipoprotein/Lipopeptide Transfection into Mammalian Cells.
Microbial lipoproteins/lipopeptides are important virulence factors for periodontal diseases. The membrane lipoproteins from Mycoplasma salivarium or Tannerella forsythia can be easily extracted by exploiting a characteristic feature of Triton X-114: its aqueous nature at low temperatures (0-4 °C), which is absent at room temperature (25-37 °C). Transfection of these lipopeptides into macrophages was performed using the protein transfection reagent, PULSin.


Kidney-lung cross-talk and acute kidney injury.
There is a growing appreciation for the role that acute kidney injury (AKI) plays in the propagation of critical illness. In children, AKI is not only an independent predictor of morbidity and mortality, but is also associated with especially negative outcomes when concurrent with acute lung injury (ALI). Experimental data provide evidence that kidney-lung crosstalk occurs and can be bidirectionally deleterious, although details of the precise molecular mechanisms involved in the AKI-ALI interaction remain incomplete. Clinically, ALI, and the subsequent clinical interventions used to stabilize gas exchange, carry consequences for the homeostasis of kidney function. Meanwhile, AKI negatively affects lung physiology significantly by altering the homeostasis of fluid balance, acid-base balance, and vascular tone. Experimental AKI research supports an "endocrine" role for the kidney, triggering a cascade of extra-renal inflammatory responses affecting lung homeostasis. In this review, we will discuss the pathophysiology of kidney-lung crosstalk, the multiple pathways by which AKI affects kidney-lung homeostasis, and discuss how these phenomena may be unique in critically ill children. Understanding how AKI may affect a "balance of communication" that exists between the kidneys and the lungs is requisite when managing critically ill children, in whom imbalance is the norm.


Superior catalytic activity of Pt/carbon nanohorns nanocomposites toward methanol and formic acid oxidation reactions.
Pt nanoparticle-loaded carbon nanohorns (Pt/CNHs) nanocomposites were synthesized by using formic acid as reducing agent at room temperature. Taking the advantage of the high surface area and excellent electronic conductivity, CNHs were used as support without any pretreatments for the enhancement of catalytic performance. By adjusting the feeding amount of H2PtCl6, the mass, size and distribution of Pt nanoparticles could be effectively controlled on CNHs. Compared with commercial Pt/C, the synthesized Pt/CNHs exhibit higher catalytic activity and improved long-term stability toward both methanol and formic acid oxidations. Among the Pt/CNHs, 13% wt. Pt/CNHs exhibit the best catalytic performances for the small size (2.4 nm) and uniform distribution of Pt NPs on CNHs. Our work reveals the superior catalytic performance of Pt/CNHs which may be a promising substitute for commercial Pt/C.


Up-regulation of reactivity and survival genes in astrocytes after exposure to short duration overpressure.
Gurdjian et al. proposed decades ago that pressure gradients played a major factor in neuronal injury due to impact. In the late 1950s, their experiments on concussion demonstrated that the principal factor in the production of concussion in animals was the sudden increase of intracranial pressure accompanying head injury. They reported the increase in pressure severity correlated with an increase in 'altered cells' resulting in animal death. More recently, Hardy et al. (2006) demonstrated the presence of transient pressure pulses with impact conditions. These studies indicate that short duration overpressure should be further examined as a mechanism of traumatic brain injury (TBI). In the present study, we designed and fabricated a barochamber that simulated overpressure noted in various head injury studies. We tested the effect of overpressure on astrocytes. Expressions of apoptotic, reactivity and survival genes were examined at 24, 48 and 72 h post-overpressure exposure. At 24 h, we found elevated levels of reactivity and survival gene expression. By 48 h, a decreased expression of apoptotic genes was demonstrated. This study reinforces the hypothesis that transient pressure acts to instigate the cellular response displayed following TBI.


Effect of hypolipidemia on testosterone-stimulated prostatic growth in castrated rats.
Hypolipidemia caused by Simfibrate feeding for 3 weeks reduced responses of weight and nucleic acid contents to testosterone administration in the ventral and dorsolateral prostates of castrated rats. However, the effect of testosterone on the contents of citrate, fructose, zinc and the activity of testosterone 5alpha-reductase in the glands of castrated animals was not modified by Simfibrate feeding.


Serum lipids and apolipoproteins in the rat refed after starving: influence of the molecular form of nitrogen (protein, peptides, or free amino acids).
Efficient treatment of deep denutrition should promote the restoration of normal intestinal villous structure and the return to a positive nitrogen balance. To determine whether the plasma measurement of lipoproteins could serve as sensitive indexes of villous architecture and/or nitrogen balance, these parameters were compared in rats starved for three days and refed three types of diets containing either whey proteins (WP), whey protein hydrolysate (WPH), or amino acids, known to differ in their capacity to promote restoration of normal villous architecture. Starvation lowered the concentration of triglycerides and phospholipids but not cholesterol. Apolipoprotein AI and AIV concentrations were also significantly lowered (30% and 40%, respectively), but ApoE was significantly increased by 40%. Upon refeeding with all three diets, plasma lipids progressively returned to control values except for triglycerides, which were significantly elevated by the protein and peptide diets. Apoprotein AI continued to decrease for 24 hours on the peptide and amino acid diets. Control levels were restored in all groups after 48 hours. ApoAIV increased progressively in parallel with the restoration of the intestinal mucosa; after 48 hours of refeeding, plasma concentrations of apo AIV were significantly correlated with jejunal villous height and protein content (P less than .01). ApoE was depressed below control levels in the WP and WPH groups at 24 and 48 hours and restored only after 96 hours. Because ApoE was affected, both in the fed state and during refeeding by the form of dietary nitrogen, it may prove to reflect nitrogen balance and/or insulin: glucagon balance.(ABSTRACT TRUNCATED AT 250 WORDS)


Natural Intestinal Protozoa in Rodents (Rodentia: Gerbillinae, Murinae, Cricetinae) in Northwestern Iran.
Majority of parasitic infections in rodents have zoonotic importance. This study aimed to determine the frequency and intensity of intestinal protozoa infections of rodents including Meriones persicus, Mus musculus and, Cricetulus migratorius. This survey was conducted in Meshkin Shahr district in northwestern Iran from Mar. to Dec. of 2014. Intestinal samples of 204 rodents including M. persicus (n=117), M. musculus (n=63) and C. migratorius (n=24) were parasitologically examined. Formalin-ether concentration method was done for all of rodents stool samples and observed with light microscope. All of suspected cases were stained with trichorome staining Method. Cultivation in dichromate potassium 2.5% was carried out for all of coccidian positive samples. Acid fast and aniline blue staining methods were used for detecting of coccidian oocysts and intestinal microsporidial spores, respectively. About 121(59.3%) of the caught rodents were generally infected with intestinal protozoa. Entamoeba muris 14(6.9%), Trichomonas muris 55(27.0%), Chilomastix betencourtti 17 (8.3%), Giardia muris 19(9.3%), Eimeria spp. 46(22.5%), Isospora spp. 4(2%) and Cryptosporidium spp. 1(0.5%) were found from the collected rodents. Microsporidian spores were identified in 63 (31%) out of the 204 collected rodents using aniline blue staining method. Since some of the infections are zoonotic importance thus, control of rodents can be decreased new cases of the parasitic zoonoses in humans.


Get Out of Jail: Managing an Entrapped Balloon Using Subintimal Plaque Modification.
Balloon entrapment is a potentially fatal complication of percutaneous coronary intervention. This report describes the use of subintimal plaque modification for the management of entrapped balloons. This technique, commonly done during chronic total occlusion angioplasty, was used successfully to retrieve the balloon. (Level of Difficulty: Advanced.).


The economic case for meeting employees' needs.
The purpose of this article was to demonstrate that health care organisations stand to benefit financially by accommodating the needs of nursing staff. Nurse turnover results in major financial losses in health care, and inadequate staffing resulting from turnover negatively affects patient outcomes, which further drives up health care costs. Strategies to limit nurse turnover are available and crucial in the quest for health care sustainability. Economic theory was presented to underpin evidence from business, education, and health disciplines literature, and from case studies of industry best practices in employee retention. This multidisciplinary analysis was applied to the retention of nurses in health care organisations. Significant reductions in nurse turnover lead to considerable financial benefit to employers. Reductions can be achieved when employers accommodate the needs of their staff. Further investigation of specific incentive models, and the transferability of those models, is needed. Incentive programmes may be matched to specific nurse needs to decrease turnover. Nursing leaders have the opportunity to discover the unique need of their workforces and invest in incentive programmes to fulfil those needs.


Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment.
The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.


Study Selection Bias and Racial or Ethnic Disparities in Estimated Age at Onset of Cardiometabolic Disease Among Midlife Women in the US.
Racial disparities in cardiometabolic health are consistently observed in cohort studies. However, most studies neither evaluate differences in age at onset nor account for systematic exclusion stemming from "weathering" (accelerated health declines for minoritized groups due to structural social and economic marginalization). To evaluate racial or ethnic disparities in age at onset of 4 cardiometabolic outcomes (hypertension, isolated systolic hypertension [ISH], insulin resistance [IR], and diabetes), accounting for multiple forms of potential selection bias. This cohort study used data from the Study of Women's Health Across the Nation longitudinal cohort (1995-2016) and a cross-sectional screening sample (1995-1997). Data were analyzed from July 2019 to October 2021. Participants were eligible for the cohort if they were aged 42 to 52 years, had not received hormone therapy in the past 3 months, were not pregnant, had an intact uterus and at least 1 ovary, and were premenopausal or early perimenopausal (most recent menses ≤3 months). Self-reported racial or ethnic group (Black, Chinese, Hispanic, Japanese, or White). The main outcomes were hypertension (systolic blood pressure [BP] ≥140 mm Hg and diastolic BP ≥90 mm Hg or use of antihypertensive medication), ISH (systolic BP ≥140 mm Hg and diastolic BP <90 mm Hg or use of antihypertensive medication), IR (homeostasis model assessment for IR value >5.9 or insulin use), and diabetes (fasting serum glucose level ≥126 mg/dL [to convert to mmol/L, multiply by 0.0555], use of insulin or oral antidiabetic medication, or physician diagnosis). Selection into the cohort was addressed via inverse probability weighting and interval-censored survival models and selection out via multiple imputation. Accelerated failure time models were used to examine racial or ethnic differences in age at disease onset and estimate the median age at onset. A total of 3302 women were included in the study, with a median age of 46.2 years (range, 42-52 years) at baseline. In the sample, 42.6% had a bachelor's degree or higher and 36.3% self-rated their health as "very good" at baseline; 23.9% had hypertension, 43.7% had ISH, 13.5% had IR, and 4.6% had diabetes at baseline. Hypertension occurred a median of 5.0 years (95% CI, 5.4-5.5 years) earlier and metabolic outcomes (diabetes and IR) a median of 11.3 years (95% CI, 9.7-12.9 years) earlier for Black and Hispanic women vs White women; ISH occurred a median of 7.7 years (95% CI, 7.3-8.1 years) earlier for Black women vs White women. Adjustment for selection was associated with a mean 20-year decrease in estimated median age at onset, with greater decreases among Black and Hispanic women. In this multiracial cohort of midlife women, failure to account for selection biases, especially at study onset, was associated with falsely high estimates of age at cardiometabolic onset, with greater misestimation among Black and Hispanic women. The results suggest that hypertension and metabolic interventions, particularly for Black and Hispanic women, should be targeted to women aged as young as 30 years for hypertension and 40 years for metabolic interventions. Considering the timing of disease and fully addressing inherent selection biases in research are critical to understanding aging and disease risk, especially for racial and ethnic minoritized populations.


A novel use of the discrete templated notes within an electronic health record software to monitor resident supervision.
Monitoring the supervision of residents can be a challenging task. We describe our experience with the implementation of a templated note system for documenting procedures with the aim of enabling automated, discrete, and standardized capture of documentation of supervision of residents performing floor-based procedures, with minimal extra effort from the residents. Procedural note templates were designed using the standard existing template within a commercial electronic health record software. Templates for common procedures were created such that residents could document every procedure performed outside of the formal procedural areas. Automated reports were generated and letters were sent to noncompliers. A total of 27 045 inpatient non-formal procedural area procedures were recorded from August 2012 to June 2014. Compliance with NoteWriter template usage averaged 86% in the first year and increased to 94.6% in the second year ( P = .0055). Initially, only 12.5% of residents documented supervision of any form. By the end of the first year, this was above 80%, with the gains maintained into the second year and beyond. Direct supervision was documented to have occurred where required in 62.8% in the first year and increased to 99.8% in the second year ( P = .0001) after the addition of hard stops. Notification of attendings prior to procedures was documented 100% of the time by September 2013. Letters sent to errant residents decreased from 3.6 to 0.83 per 100 residents per week. The templated procedure note system with hard stops and integrated reporting can successfully be used to improve monitoring of resident supervision. This has potential impact on resident education and patient safety.


Ontogenic development of the suppressed secondary response to native dextran.
The ontogenic development of the plaque-forming cell (PFC) response to the thymus-independent (TI) antigen alpha 1-6 native dextran B512 was studied to determine when the first minimal amounts of anti-dextran antibodies are formed. Substantial antibody responses to certain other TI polysaccharide antigens arise during the first month of life, whereas the development of the response to native dextran has been found to be conspicuously delayed in high-responder mice. Results indicated that CBA mice began to produce minimal amounts of anti-dextran antibodies between 15 and 21 days of age, and the development continued progressively until peak levels were reached at 90 days of age. The alpha 1-6 native dextran system is also one of the few murine models in which endogenous anti-idiotypic antibodies are formed subsequent to anti-dextran production. It has been shown that the anti-idiotypic antibodies are responsible for specific inhibition of secondary PFC responses to dextran. Suppression of the secondary response was used here to ascertain whether the initial low level of anti-dextran antibodies elicited in 15-day-old animals was sufficient to lead to inhibition of the secondary response. The approach confirmed the initiation of anti-dextran production at 15-21 days of age and indicated that the small amount of anti-dextran antibodies produced at this age was sufficient to induce the mechanism leading to suppression of the secondary response.


The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review.
Colorectal cancer (CRC) is a highly prevalent disease with poor prognostic outcomes if not diagnosed in early stages. Current diagnosis techniques are either highly invasive or lack sufficient sensitivity. Thus, identifying diagnostic biomarkers of CRC with high sensitivity and specificity is desirable. Metabolomics represents an analytical profiling technique with great promise in identifying such biomarkers and typically represents a close tie with the phenotype of a specific disease. We thus conducted a systematic review of studies reported from January 2012 to July 2021 relating to the detection of CRC biomarkers through metabolomics to provide a collection of knowledge for future diagnostic development. We identified thirty-seven metabolomics studies characterizing CRC, many of which provided metabolites/metabolic profile-based diagnostic models with high sensitivity and specificity. These studies demonstrated that a great number of metabolites can be differentially regulated in CRC patients compared to healthy controls, adenomatous polyps, or across stages of CRC. Among these metabolite biomarkers, especially dysregulated were certain amino acids, fatty acids, and lysophosphatidylcholines. Additionally, we discussed the contribution of the gut bacterial population to pathogenesis of CRC through their modulation to fecal metabolite pools and summarized the established links in the literature between certain microbial genera and altered metabolite levels in CRC patients. Taken together, we conclude that metabolomics presents itself as a promising and effective method of CRC biomarker detection.


Improvements in G protein-coupled receptor purification yield light stable rhodopsin crystals.
G protein-coupled receptors (GPCRs) represent the largest family of transmembrane signaling proteins and are the target of approximately half of all therapeutic agents. Agonist ligands bind their cognate GPCRs stabilizing the active conformation that is competent to bind G proteins, thus initiating a cascade of intracellular signaling events leading to modification of the cell activity. Despite their biomedical importance, the only known GPCR crystal structures are those of inactive rhodopsin forms. In order to understand how GPCRs are able to transduce extracellular signals across the plasma membrane, it is critical to determine the structure of these receptors in their ligand-bound, active state. Here, we report a novel combination of purification procedures that allowed the crystallization of rhodopsin in two new crystal forms and can be applicable to the purification and crystallization of other membrane proteins. Importantly, these new crystals are stable upon photoactivation and the preliminary X-ray diffraction analysis of both photoactivated and ground state rhodopsin crystals are also reported.


Corrigendum: Successful non-operative treatment of eruptive keratoacanthomas refractory to excision.
The original article was published on March 15, 2020 and corrected on June 15, 2020. The revised version of the article corrects an Author's name. The changes appear in the revised online PDF copy of this article.


Imatinib mesylate suppresses cytokine synthesis by activated CD4 T cells of patients with chronic myelogenous leukemia.
Although imatinib mesylate (IM) is highly effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia (CML), it is known to suppress T-cell proliferation in vitro. As cytokines are required for T-cell proliferation, we investigated the effects of IM on cytokine synthesis by T cells of CML patients by assessing cytokine synthesis by activated CD4+ and CD8+ T cells in vitro. The activation of T cells in the whole blood of IM-treated patients (CML-IM) with Staphylococcus enterotoxin B resulted in significantly lower percentages of CD4+ T cells that synthesized interleukin 2 (P = 0.017), interferon-gamma (P = 0.010), and tumor necrosis factor-alpha (P = 0.009) than did the activated T cells of control subjects. The addition of exogenous IM to the cultures of peripheral blood mononuclear cells of CML-IM patients reduced Th1 cytokine synthesis by the CD4+ T cells. Furthermore, IM therapy at clinical doses suppressed the tyrosine phosphorylation of ZAP70. These findings suggest that inhibition of ZAP70 signaling pathway and suppression of Th1 cytokine synthesis by CD4+ T cells required the presence of IM at the time of T-cell activation through the T-cell receptor.


The effects of aging and oxidative stress on psychomotor and cognitive behavior.
Decrements in motor and cognitive function occur in aging, possibly due to oxidative stress-induced damage to the brain. Declines in antioxidant defense mechanisms have been postulated as a causative factor in these age-related decrements, however a clear link between oxidative stress (OS) and behavioral changes in aging has yet to be established. This review shows that age-validated psychomotor and cognitive tests are sensitive to behavioral deficits under different models of OS, including: 1) decreasing OS protection by depleting glutathione and then increasing the OS with dopamine; 2) 100% oxygen exposure; and 3) radiation. Furthermore, interventions that reduce OS result in concurrent improvements in age-associated behavioral deficits. Therefore, age-related changes in behavior may result from an inability to cope with OS that occurs throughout the life-span.


[Super-selective pump-insertion into the target artery and regional intraarterial infusion chemotherapeutant and immunizator in treatment of the latter gastrointestinal cancer].
To evaluate the effect of operative selective pump-insertion into the tumorous target artery, postoperative regional infusion chemotherapeutant and immunizator for treatment the latter gastrointestinal cancer. The effect of operative super-selective pump-insertion into the tumorous nutritious artery, postoperative regional infusion chemotherapeutant and immunizator for treatment 88 cases patients suffering from irremovable gastrointestinal cancer was observed. Of them, 45 cases were gastric cancer, 31 cases were rectal cancer, 11cases were colic cancer. Complete response 2 case; Part response 77 cases, 11 cases patients had received secondary resection after intraarterial chemotherapy. Non chang 9 cases; effective rates reach to 89.8%. One, two and three years survival rates were 86.4%, 30.7% and 10.2%. Average survival period were 21.5 mouths. Super-selective pump-insertion into the artery and regional intraarterial chemotherapy is an efficient way in treatment of the latter gastrointestinal cancer, which can delay the survival period of patients with tumor, and increase the resectable rate.


The role of transcriptional and translational mechanisms in flumazenil-induced up-regulation of recombinant GABA(A) receptors.
The aim of this study was to further elucidate the mechanisms involved in adaptive changes of GABA(A) receptors following prolonged exposure to flumazenil, the antagonist of benzodiazepine binding sites on GABA(A) receptors. The effects of prolonged flumazenil treatment were studied on recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors stably expressed in human embryonic kidney (HEK 293) cells. Using radioligand binding experiments we found enhancement in the maximum number of [(3)H]muscimol labeled binding sites in different preparations of HEK 293 cells. The parallel increase of [(3)H]flunitrazepam binding sites in the membranes was reduced in the presence of actinomycin D and cycloheximide, inhibitors of RNA and protein synthesis, respectively. Chronic flumazenil also raised the steady-state level of mRNA encoding alpha(1) receptor subunit. The results suggest that the up-regulation of GABA(A) receptors, observed after prolonged flumazenil treatment is at least partly due to increased de novo synthesis of receptor proteins at both transcriptional and translational level.


Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs.
Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors.


Relationship between oestrogen-receptor content and histological grade in human primary breast tumours.
A series of 300 patients presenting consecutively with primary operable breast cancer has been studied. A significant correlation was found between oestrogen-receptor (ER) content and histological grade: the better-differentiated tumours rarely lacked receptor. This correlation was significant only in women defined as post-menopausal. Data on early recurrence of disease indicate a worse prognosis for women in whom primary tumours are ER-.


Advocating for Early-Career Nurse Innovators: Modeling the Institute of Medicine Report.
The Future of Nursing: Leading Change, Advancing Health was published by the of Medicine (IOM) of the National Academies in 2011. The Missouri Nurses Foundation and Missouri nurses modeled a sustainable project, the Early Career Nurse Innovator Project, exemplifying the intent of that report. The Missouri Nurses Foundation Executive Board comprises experienced nurses, nurse educators, nurses in other leadership roles, retired nurses, public members of the board, and administrative support staff. This article describes a project that was developed, implemented, and evaluated to recognize and encourage early-career nurses who have designed and led innovations to improve and promote the health of Missourians. Five of these early-career nurses were the recipients of monetary awards to encourage future innovations; the second recognition cycle is in the planning phase. Through the work of the Missouri Nurses Foundation, the scholarship of bedside nurses was recognized.


Systematic review of health state utility values in metastatic non-small cell lung cancer with a focus on previously treated patients.
Health state utility values (HSUVs) are an important input to economic evaluations and the choice of HSUV can affect the estimate of relative cost-effectiveness between interventions. This systematic review identified utility scores for patients with metastatic non-small cell lung cancer (mNSCLC), as well as disutilities or utility decrements relevant to the experience of patients with mNSCLC, by treatment line and health state. The MEDLINE®, Embase and Cochrane Library databases were systematically searched (September 2016) for publications describing HSUVs in mNSCLC in any treatment line. The EQ-5D website, the School of Health and Related Research Health Utilities Database (ScHARRHUD) and major pharmacoeconomic and clinical conferences in 2015-2016 were also queried. Studies in adults with previously treated mNSCLC were selected for further analysis. The information extracted included study design, description of treatment and health state, respondent details, instrument and tariff, HSUV or (dis) utility decrement estimates, quality of study, and appropriateness for use in economic evaluations. Of 1883 references identified, 36 publications of 34 studies were included: 19 reported EQ-5D scores; eight reported HSUVs from valuations of vignettes made by members of the public using standard gamble (SG) or time trade-off (TTO); two reported SG or TTO directly elicited from patients; two reported EQ-5D visual analogue scale scores only; one reported Assessment of Quality of Life instrument scores; one reported HSUVs for caregivers to patients with mNSCLC using the 12-item Short-Form Health Survey; and one estimated HSUVs based on expert opinion. The range of HSUVs identified for comparable health states showed how differences in study type, tariff, health state and the measures used can drive variation in HSUV estimates. This systematic review provides a set of published HSUVs that are relevant to the experience of adult patients previously treated for mNSCLC. Our review begins to address the challenge of identifying reliable estimates of utility values in mNSCLC that are suitable for use in economic evaluations, and also highlights how varying estimates result from differences in methodology.


Phenoloxidase and cytotoxicity in the compound ascidian Botryllus schlosseri.
The vacuoles of morula cells (MC) of the colonial ascidian Botryllus schlosseri contain phenoloxidase (PO). As the release of their vacuolar content at the border of incompatible contacting colonies is associated with the formation of necrotic masses which characterize the rejection reaction, the role of PO in Botryllus cytotoxicity was investigated. When hemocytes are incubated with blood plasma from incompatible (heterologous) colonies, MC degranulate and, after 60 min, the cytotoxicity index becomes significantly greater than that observed in controls incubated with autologous plasma. The rise in cell mortality is completely inhibited by the addition of PO inhibitors sodium benzoate, tropolone and phenylthiourea, and serine protease inhibitors phenylmethylsulfonyl fluoride, benzamidine, N-tosyl-L-phenylalanine chloromethyl ketone and N-tosyl-L-lysine chloromethyl ketone. The addition of either reducing agents L-cysteine and ascorbic acid or reactive oxygen species scavenger enzymes superoxide dismutase and catalase has a similar effect. Significant inhibition of cytotoxicity is also observed with the quinone scavenger, 3-methyl-2-benzothiazolinone hydrazone. In the presence of sodium benzoate and phenylthiourea, there is a significant reduction in the number, size and color intensity of necrotic masses along the contact border of incompatible colonies. A significant increase in superoxide anion production, completely inhibited by sodium benzoate, is observed when hemocytes are incubated with heterologous blood plasma. These results indicate that: (i) PO is the enzyme responsible for the cytotoxicity observed in both hemocyte cultures and rejection reactions; (ii) PO is present inside MC vacuoles as a proenzyme which is activated, upon release, by humoral proteases; (iii) cytotoxicity appears to be mainly due to oxidative stress generated by PO during oxidation of polyphenols to quinones without the involvement of other oxidases such as NADPH oxidase and peroxidase.


Releasing the Brake on Oncolytic Viral Therapy.
Oncolytic virus that selectively targets and eradicates tumor cells and immune checkpoint blockade that unleashes host antitumor immune responses show synergistic effects against cancer. This combination holds great promise for future treatment of a broad range of cancers in patients. Clin Cancer Res; 21(24); 5417-9. ©2015 AACR.See related article by Rojas et al., p. 5543.


High electrochemical performance of Fe2O3@OMC for lithium-ions batteries.
Fe2O3@OMC (ordered mesoporous carbon) is synthesized using Fe-MOFs (metal-organic frameworks). The Fe2O3@OMC pore size is mostly concentrated at approximately 2-4 nm. Compared to traditional OMC or carbonized Fe-MOFs, Fe2O3@OMC demonstrates a higher capacity (the capacity remains at 1176.6 mAh g-1 after 500 cycles under a current density of 0.1 A g-1) and a longer cycle life. The first cycle capacity of Fe2O3@OMC is ultrahigh at 2448.6 mAh g-1, and the reversible capacity is 1294.1 mAh g-1. Fe2O3@OMC maintains a good performance under current densities of 0.1 A g-1, 0.2 A g-1, 0.5 A g-1, 1 A g-1, 2 A g-1, and 5 A g-1, with electric capacities of 1100.8 mAh g-1, 1017.6 mAh g-1, 849.3 mAh g-1, 690.7 mAh g-1, 506.7 mAh g-1, and 272.1 mAh g-1, respectively. Thus, the material has good rate performance. Combining iron oxide and MOFs is helpful to improve the capacity performance.


Retinoid receptors and acute promyelocytic leukaemia.
While a great deal has been learned about APL over the last few years, many important questions remain unanswered. It has become clear that the PML/RAR-alpha fusion protein is expressed in most cases of APL, and this protein presumably contributes to leukaemia initiation and/or progression. PML/RAR-alpha appears to specifically block the further differentiation of myeloid progenitor cells, although the mechanism of its action is not known. It may inhibit the transcription of RAR- or PML-regulated genes, in which case expression must be restored in the presence of therapeutic RA concentrations. However, the possibility remains that PML/RAR-alpha may have a novel function. In order to elucidate the molecular pathogenesis of APL, several important questions remain to be answered. These include whether PML is a transcription factor; the identification of its target genes and response elements, and the role of PML/RAR-alpha and RA in their regulation. Also whether the expression of PML/RAR-alpha in bone marrow cells (either by itself or in combination with other oncogenes) alters their tumourigenicity or differentiation potential. It is also important to determine the function(s) of PLZF and PLZF/RAR-alpha, and determine whether other APL patients with mutations involving PML or RAR-alpha (but not both) respond to therapy with all-trans-RA. Finally, it is important both for the understanding of the molecular biology of APL and its therapy, to determine the effects of other regulatory factors involved in the control of myeloid cell differentiation such as granulocyte colony stimulation factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) on APL cells in vitro and in vivo, both at presentation and in the RA-resistant patients in relapse.


Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn.
Capsaicin depletes the sensory neuropeptide substance P (SP) in the rat due to a combination of neuron loss and decreased synthesis in the surviving cells. Resiniferatoxin (RTX) mimics most, but not all, capsaicin actions. In the present study, the effects of RTX (300 microg/kg, s.c.) were examined on mRNA levels for SP and its receptor in the adult rat. The percentage of dorsal root ganglia (DRG) neuronal profiles showing an in situ hybridization signal for preprotachykinin mRNAs encoding SP was not altered following RTX treatment (up to 8 weeks), though the signal became perceptibly weaker. In accord, 2 weeks after RTX administration a 60% decrease was observed in the steady-state levels of SP-encoding mRNAs using Northern blot analysis, leaving the ratio of beta- and gamma-preprotachykinin mRNAs unchanged. No change was, however, observed in mRNA levels encoding tachykinins NK-1 receptors in the dorsal horn, the spinal targets for SP. The present findings suggest that RTX does not kill SP-positive DRG neurons, though it suppresses the synthesis of SP. Since RTX treatment does not alter NK-1 receptor expression, this reduced SP synthesis is likely to play a central role in the analgesic actions of RTX.


Orotracheal administration of contrast agents: a new protocol for brain tumor targeting.
The development of new non-invasive diagnostic and therapeutic approaches is of paramount importance in order to improve the outcome of patients with glioblastoma (GBM). In this work we investigated a completely non-invasive pre-clinical protocol to effectively target and detect brain tumors through the orotracheal route, using ultra-small nanoparticles (USRPs) and MRI. A mouse model of GBM was developed. In vivo MRI acquisitions were performed before and after intravenous or orotracheal administration of the nanoparticles to identify and segment the tumor. The accumulation of the nanoparticles in neoplastic lesions was assessed ex vivo through fluorescence microscopy. Before the administration of contrast agents, MR images allowed the identification of the presence of abnormal brain tissue in 73% of animals. After orotracheal or intravenous administration of USRPs, in all the mice an excellent co-localization of the position of the tumor with MRI and histology was observed. The elimination time of the USRPs from the tumor after the orotracheal administration was approximately 70% longer compared with intravenous injection. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify and longitudinally monitor the development of GBMs. The absence of ionizing radiation and high resolution of MRI, along with the complete non-invasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge, this is the first time that the advantages of a needle-free orotracheal administration route have been demonstrated for the investigation of the pathomorphological changes due to GBMs.


Affinity column purification of amylases on protein inhibitors from wheat kernel.
An affinity column was devised for the purification of a large number of amylases inhibited by the albumin from wheat kernel. The procedure involved linking the protein inhibitors from wheat to Sepharose and then specifically eluting the amylase adsorbed to the gel with a high concentration of maltose. By this procedure, the amylases from Tenebrio molitor L. (yellow mealworm) larvae and chicken pancreas were purified to homogeneity with good yields for the first time, as shown by both alkaline and acidic electrophoresis. Human saliva alpha-amylase, purified by the same procedure, showed specific activity and electrophoretic patterns similar to those obtained by other workers with different techniques.


Tutorial. Surface electromyogram (sEMG) amplitude estimation: Best practices.
This tutorial intends to provide insight, instructions and "best practices" for those who are novices-including clinicians, engineers and non-engineers-in extracting electromyogram (EMG) amplitude from the bipolar surface EMG (sEMG) signal of voluntary contractions. A brief discussion of sEMG amplitude extraction from high density sEMG (HDsEMG) arrays and feature extraction from electrically elicited contractions is also provided. This tutorial attempts to present its main concepts in a straightforward manner that is accessible to novices in the field not possessing a wide range of technical background (if any) in this area. Surface EMG amplitude, also referred to as the sEMG envelope [often implemented as root mean square (RMS) sEMG or average rectified value (ARV) sEMG], quantifies the voltage variation of the sEMG signal and is grossly related to the overall neural excitation of the muscle and to peripheral parameters. The tutorial briefly reviews the physiological origin of the voluntary sEMG signal and sEMG recording, including electrode configurations, sEMG signal transduction, electronic conditioning and conversion by an analog-to-digital converter. These topics have been covered in greater detail in prior tutorials in this series. In depth descriptions of state-of-the-art methods for computing sEMG amplitude are then provided, including guidance on signal pre-conditioning, absolute value vs. square-law detection, selection of appropriate sEMG amplitude smoothing filters and attenuation of measurement noise. The tutorial provides a detailed list of best practices for sEMG amplitude estimation.