Carrier-Envelope-Phase Characterization for an Isolated Attosecond Pulse by Angular Streaking.
The carrier envelope phase (CEP) is a crucial parameter for a few-cycle laser pulse since it substantially determines the laser waveform. Stepping forward from infrared to extreme ultraviolet (EUV) pulses, we propose a strategy to directly characterize the CEP of an isolated attosecond pulse (IAP) by numerically simulating the tunneling ionization of a hydrogen atom in a combined IAP and phase-stabilized circularly polarized IR laser pulse. The fine modulations of the combined laser fields, due to the variation of the CEP of the IAP, are exponentially enlarged onto the distinct time-dependent tunneling ionization rate. Electrons released at different time with distinct tunneling ionization rates are angularly streaked to different directions. By measuring the resulting photoelectron momentum distribution, the CEP of the IAP can be retrieved. The characterization of the CEP of an IAP will open the possibility of capturing sub-EUV-cycle dynamics.


Metabolomics profiling of maternal and umbilical cord blood in normoglycemia macrosomia.
Background: Macrosomia is a common disorder that occurs during pregnancy. We investigated the comprehensive metabolite profiles of pregnant maternal and fetal sera in normoglycemic macrosomia in a Chinese population. Methods: Forty pregnant women and their fetuses were included in the study (twenty macrosomia patients and twenty normal-weight controls). Maternal and umbilical cord serum metabolites were identified using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Results: In total, 203 metabolites were identified. Lipids and lipid-like molecules were the predominant metabolites. Fifty-three metabolites with significant differences were obtained in the maternal samples. In the macrosomia group, the levels of docosahexaenoic acid, eicosapentaenoic acid, and arachidonic acid were significantly higher than those in the control group. Umbilical cord serum samples were obtained for 24 different metabolites. The maternal-fetal gradient of polyunsaturated fatty acids was decreased in the macrosomia group. Aconitic acid, citric acid, isocitric acid, 2-methylhexanoic acid, and 12-hydroxystearic acid were the common differential metabolites in the maternal and umbilical cord serum samples. Conclusion: There were obvious metabolic abnormalities in the sera of pregnant women and fetuses with macrosomia. Lipids and lipid-like molecules were the predominant differential metabolites but had different classifications in the maternal and umbilical cord serum. These results may provide new insights into the long-term metabolic disorders associated with macrosomia.


Ten-Year Prospective Follow-Up of Institutionalized Patients With Diabetes in a Long-Term Care Home.
Clinical practice recommendations advise individualizing diabetes treatment for elderly people, especially those living in long-term care facilities. Elderly patients face one of two main risks: either excessive treatment leading to hypoglycemia or insufficient treatment leading to progression of complications and excess mortality. This article describes a 10-year prospective observational study of people with diabetes in a long-term care home to determine the effect of routine glucose monitoring and monthly evaluation by a diabetes specialist with a goal of improving A1C. Its findings suggest that minimal glucose monitoring and monthly medical follow-up can optimize patient outcomes and help to maintain quality of life without over-medicalization of older people with diabetes in institutional settings.


Shb gene knockdown increases the susceptibility of SVR endothelial tumor cells to apoptotic stimuli in vitro and in vivo.
The Shb adapter protein is an Src homology 2-domain containing signaling intermediate operating downstream of several tyrosine kinase receptors, including vascular endothelial growth factor receptor-2. Shb is multifunctional and apoptosis is one response that Shb regulates. Inhibition of angiogenesis can be used in cancer therapy, and one way to achieve this is by inducing endothelial cell apoptosis. The angiosarcoma cell line SVR is of endothelial origin and can be used as a tool for studying in vivo inhibition of angiogenesis, and we thus employed an Shb-knockdown strategy using an inducible lentiviral system to reduce Shb levels in SVR cells and to study their responses. Shb knockdown increases the susceptibility of SVR cells to the apoptotic agents, cisplatin and staurosporine. Simultaneously, Shb knockdown causes reduced focal adhesion kinase (FAK) activation, monitored as phosphorylation of the regulatory residues tyrosines 576/577. No detectable effects on Akt or extracellular signal-regulated kinase activity were noted. The altered FAK activity coincided with an elongated cell phenotype that was particularly noticeable in the presence of staurosporine. In order to relate the effects of Shb knockdown to in vivo tumorigenicity, cells were exposed to the angiogenesis inhibitor honokiol, and again the cells with reduced Shb content exhibited increased apoptosis. Tumor growth in vivo was strongly reduced in the Shb-knockdown cells upon honokiol treatment. It is concluded that Shb regulates apoptosis and cell shape in tumor endothelial cells via FAK, and that Shb is a potential target for inhibition of angiogenesis.


The role of radioimmunodetection in the management of testicular cancer.
Five patients with testicular cancer received an intravenous injection of between 1 and 2.5 mCi of iodine 131-labeled antibody to human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP), followed by total-body photoscanning to visualize areas of abnormal radioactivity. Blood-pool and nontarget sites of radioactivity were reduced by subtracting the images derived by injection of technetium Tc 99m-labeled components from the iodine 131 scans. The HCG-immune scintiscans proved helpful in tumor localization and in the selection of appropriate therapy, while the AFP scan presented corroborative evidence of widespread tumor. Elevated serum levels of these two markers did not hinder successful tumor detection and localization by this method of radioimmunodetection. Cancer radioimmunodetection with antibodies to HCG and to AFP appears to be a useful procedure for the pretreatment and posttreatment evaluation of patients with testicular cancer and can reveal sites of tumor not detected by other methods.


Influence of a constriction in the near field of the vocal folds: physical modeling and experimental validation.
The involvement of the ventricular folds is often observed in human phonation and, in particular, in pathological and or some throat-singing phonation. This study aims to explore and model the possible aerodynamic interaction between the ventricular and vocal folds using suitable in vitro setups allowing steady and unsteady flow conditions. The two experimental setups consist of a rigid and a self-oscillating vocal-fold replica, coupled to a downstream rigid ventricular-fold replica in both cases. A theoretical flow modeling is proposed to quantify the aerodynamic impact of the ventricular folds on the pressure distribution and thereby on the vocal-fold vibrations. The mechanical behavior of the vocal folds is simulated by a distributed model accounting for this impact. The influence of the ventricular constriction is measured in both flow conditions and compared to the model outcome. This study objectively evaluates the additional pressure drop implied by the presence of a ventricular constriction in the larynx. It is demonstrated that such constriction can either facilitate or impede the glottal vibrations depending on the laryngeal geometrical configuration. The relevance of using static or dynamic vocal-fold replicas is discussed.


The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias.
Neurofilament light chain protein (NfL) is a surrogate biomarker of neurodegeneration that has never been systematically tested, either alone or in combination with other biomarkers, in atypical/rapidly progressive neurodegenerative dementias (NDs). Using validated, commercially available enzyme-linked immunosorbent assay kits, we measured cerebrospinal fluid (CSF) NfL, total tau (t-tau), phosphorylated tau, and β-amyloid 42 in subjects with a neuropathological or clinical diagnosis of prion disease (n = 141), Alzheimer's disease (AD) (n = 73), dementia with Lewy bodies (DLB) (n = 35), or frontotemporal lobar degeneration (FTLD) (n = 44). Several cases with an atypical/rapidly progressive course were included in each group. We evaluated the diagnostic accuracy of every CSF biomarker and their combinations by ROC curve analyses. In each patient group CSF NfL showed higher levels than in control subjects, reaching the highest values in those with Creutzfeldt-Jakob disease (CJD). In the latter, NfL showed a divergent, subtype-specific correlation with t-tau, depending on the degree of subcortical involvement and disease duration. Most significantly, patients with classic sporadic CJD (sCJD) MM1 showed a significantly lower concentration of CSF NfL than those with sCJD MV2, despite the much higher t-tau levels and the more rapid clinical course. High NfL levels were also detected in most atypical CJD cases, showing a disease duration longer than 2 years and/or borderline/negative results in other CSF assays (e.g., 14-3-3, t-tau, and prion real-time quaking-induced conversion). Rapidly progressive/atypical cases showed higher NfL levels than typical patients in FTLD, but not in AD or DLB. NfL showed accuracy similar to that of t-tau in discriminating CJD from other NDs, but it had higher efficacy in differentiating atypical forms, especially in regard to Alzheimer's disease. The present data indicate that CSF NfL and t-tau levels reflect distinct pathophysiological mechanisms of neurodegeneration and support the clinical use of NfL as a fast screening biomarker for the differential diagnosis of atypical/rapidly progressive NDs.


Nonalcoholic fatty liver disease and age are strong indicators for atherosclerosis in morbid obesity.
Whether nonalcoholic fatty liver disease (NAFLD) can predict atherosclerosis in obese patients remains unclear. The aim of our study was to investigate the usefulness of NAFLD and other cardiometabolic parameters in predicting subclinical atherosclerosis in obese patients. We studied 314 consecutive obese subjects (223 women; mean age, 45·04 ± 9·34 years; body mass index 44·3 ± 5 kg/m(2) ) and 47 healthy lean individuals. Hepatic steatosis and atherosclerosis [carotid intima-media thickness (cIMT) >0·8 mm and/or presence of plaques] were evaluated ultrasonographically. Liver biopsies were obtained in 51 patients. In obese patients, mean c-IMT was greater in those with NAFLD (P < 0·001). Hepatic steatosis and age were independent predictors of atherosclerosis: the NAFLD-associated OR for atherosclerosis was 5·96 (95%CI, 1·60-22·25; P = 0·008) in men and 8·26 (95%CI, 4·02-16·99; P < 0·001) in women, and the age-associated OR for atherosclerosis was 1·14 (95%CI, 1·07-1·22; P < 0·001) in men and 1·12 (95%CI, 1·08-1·17; P < 0·001) in women. The sensitivity, specificity and positive and negative predictive values of steatosis for atherosclerosis were 78·70%, 70·50%, 74·00% and 75·60% (AUC = 0·840) in men ≥43·5 years and 86·90%, 52·50%, 68·80% and 76·80% (AUC = 0·761) in women ≥47·5 years, respectively. Agreement between ultrasound-diagnosed steatosis and histology was good (ICC = 0·79). Combined NAFLD and age was the strongest predictor of atherosclerosis in obesity. Nonalcoholic fatty liver disease and age may be independent risk factors for carotid atherosclerosis in obese individuals. Obese men and women with steatosis aged over 43·5 and 47·5 years, respectively, should be screened for carotid atherosclerosis. However, further evidence is necessary before suggesting an intervention based on current findings.


[Late diagnosis of a McArdle disease's case (type V glycogenosis)].
McArdle's disease is a metabolic myopathy characterized by a myophosphorylase deficiency resulting in an inability to degrade glycogen stores. We report the case of a 48 years old patient who complained since adolescence of rest and exercise myalgias and presented a chronic increased plasma creatine kinase activity. First, a maximal exercise test was performed. This test demonstrated a quasi lack of rise of respiratory exchange ratio and of blood lactate, possibly due to a glycogenolytic/glycolytic pathway deficiency. Second, a biopsy of vastus lateralis muscle was performed using Bergström needle. As expected, the analysis of mitochondrial function was normal. The in vitro screening test of the glycogenolysis/glycolysis pathway showed a lack of lactate production in presence of glycogen substrate. The study of muscular metabolism of glycogen revealed a glycogen accumulation and a decrease of active and total phosphorylase activities. These data allowed us to diagnose a type V glycogenosis, or McArdle's disease. The patient appeared heterozygous for the most frequent mutation (p.R50X).


Endovascular Embolization by Transcatheter Delivery of Particles: Past, Present, and Future.
Minimally invasive techniques to occlude flow within blood vessels, initially pioneered in the 1970s with autologous materials and subsequently advanced with increasingly sophisticated engineered biomaterials, are routinely performed for a variety of medical conditions. Contemporary interventional radiologists have at their disposal a wide armamentarium of occlusive agents to treat a range of disease processes through a small incision in the skin. In this review, we provide a historical perspective on endovascular embolization tools, summarize the current state-of-the-art, and highlight burgeoning technologies that promise to advance the field in the near future.


Multiple lineages of monkeypox virus detected in the United States, 2021-2022.
Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 US monkeypox cases: the major 2022 outbreak variant called B.1 and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.


Percutaneous coronary intervention for unprotected left main coronary artery stenosis.
Hemodynamically significant left main coronary artery stenosis (LMCA) is found in around 4% of diagnostic coronary angiograms and is known as unprotected LMCA stenosis if the left coronary artery and left circumflex artery has no previous patent grafts. Previous randomized studies have demonstrated a significant reduction in mortality when revascularization by coronary artery bypass graft (CABG) surgery was undertaken compared with medical treatment. Therefore, current practice guidelines do not recommend percutaneous coronary intervention (PCI) for such a lesion because of the proven benefit of surgery and high rates of restenosis with the use of bare metal stents. However, with the advent of drug-eluting stents (DES), the long term outcomes of PCI with DES to treat unprotected LMCA stenoses have been acceptable. Therefore, apart from the current guidelines, PCI for treatment of unprotected LMCA stenosis is often undertaken in individuals who are at a very high risk of CABG or refuse to undergo a sternotomy. Future randomized studies comparing CABG vs PCI using DES for treatment of unprotected LMCA stenosis would be a great advance in clinical knowledge for the adoption of appropriate treatment.


Decreased Tactile Sensitivity Induced by Disownership: An Observational Study Utilizing the Rubber Hand Illusion.
The sense of body ownership, the feeling that one's own body belongs to oneself, is generated from the integration of visual, tactile, and proprioceptive information. However, long-term non-use of parts of the body due to physical dysfunction caused by trauma or illness may disturb multisensory integration, resulting in a decreased sense of body ownership. The rubber hand illusion (RHI) is an experimental method of manipulating the sense of ownership (SoO). In this illusion, subjects feel as if the rubber hand in front of them were their own hand. The RHI elicits the disownership phenomenon; not only does the rubber hand feels like one's own hand, but one's own hand does not feel like one's own hand. The decrease of ownership of one's own body induced by the bodily illusion is accompanied by neurophysiological changes, such as attenuation of somatosensory evoked potential and decreases in skin temperature. If the loss of the SoO is associated with decreased neurophysiological function, the dysfunction of patients complaining of the loss of ownership can be exacerbated; appropriate rehabilitation prescriptions are urgently required. The present study attempted to induce a sense of disownership of subjects' own hands using the RHI and investigated whether the tactile sensitivity threshold was altered by disownership. Via questionnaire, subjects reported a decrease of ownership after the RHI manipulation; at the same time, tactile sensitivity thresholds were shown to increase in tactile evaluation using the Semmes-Weinstein monofilaments test. The tactile detection rate changes before and after the RHI were negatively correlated with the disownership-score changes. These results show that subjects' sense of disownership, that their own hands did not belong to them, led to decreases in tactile sensitivity. The study findings also suggest that manipulating of illusory ownership can be a tool for estimating the degree of exacerbation of sensory impairment in patients. Consideration of new interventions that optimize the sense of body ownership may contribute to new rehabilitation strategies for post-stroke sensory impairment.


UniCon3D: de novo protein structure prediction using united-residue conformational search via stepwise, probabilistic sampling.
Recent experimental studies have suggested that proteins fold via stepwise assembly of structural units named 'foldons' through the process of sequential stabilization. Alongside, latest developments on computational side based on probabilistic modeling have shown promising direction to perform de novo protein conformational sampling from continuous space. However, existing computational approaches for de novo protein structure prediction often randomly sample protein conformational space as opposed to experimentally suggested stepwise sampling. Here, we develop a novel generative, probabilistic model that simultaneously captures local structural preferences of backbone and side chain conformational space of polypeptide chains in a united-residue representation and performs experimentally motivated conditional conformational sampling via stepwise synthesis and assembly of foldon units that minimizes a composite physics and knowledge-based energy function for de novo protein structure prediction. The proposed method, UniCon3D, has been found to (i) sample lower energy conformations with higher accuracy than traditional random sampling in a small benchmark of 6 proteins; (ii) perform comparably with the top five automated methods on 30 difficult target domains from the 11th Critical Assessment of Protein Structure Prediction (CASP) experiment and on 15 difficult target domains from the 10th CASP experiment; and (iii) outperform two state-of-the-art approaches and a baseline counterpart of UniCon3D that performs traditional random sampling for protein modeling aided by predicted residue-residue contacts on 45 targets from the 10th edition of CASP. Source code, executable versions, manuals and example data of UniCon3D for Linux and OSX are freely available to non-commercial users at http://sysbio.rnet.missouri.edu/UniCon3D/ CONTACT: firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


[Monitoring antibiotic consumption in the surgery and orthopaedics].
Monitoring antibiotic consumption is a valuable tool which has been increasingly used in the last years due to the current concern with the emergence of resistant microbial strains. The present study aimed at monitoring antibiotic consumption, evaluating the economic impact of hospital antibiotic prescription and assessing the relationship between the prescribed antibiotics and the indications for either prophylactic or therapeutic use. This was a longitudinal pilot-study for which data were collected in six privately managed public hospital units during the month of May 2004, with a resulting sample of 1,122 admitted patients. We observed a prescription incidence rate of 76.9%, corresponding to a total of 1,154 dispensed antimicrobials, with a mean 71.2% of these antimicrobials being dispensed for the prophylaxis of surgical site infection (SSI). The mean cost of antibiotic courses was higher in cases of "suspected infection" (9.09 euro) or "confirmed infection" (8.74 euro) and lower in cases of "prophylaxis" (5.67 euro), a finding which is explained by the shorter mean duration of the later. There was a considerable variation among the different hospital units regarding the type of antibiotic compound that was used for SSI prophylaxis, with a mean duration of antibiotic use of 2.61 days for this indication and about half of the prophylactic regimens lasting longer than 24 hours, a fact that suggests an insufficient observation of the current recommendations for antibiotic use in SSI prophylaxis. This finding indicates the need for an investigation on the actual existence of local recommendations for SSI prophylaxis in individual hospital units and also for the evaluation of the compliance of practicing surgeons with eventually existing recommendations.


Examining the role of Indigenous primary healthcare across the globe in supporting populations during public health crises.
When health systems are overwhelmed during a public health crisis regular care is often delayed and deaths result from lapses in routine care. Indigenous primary healthcare (PHC) can include a range of programmes that incorporate treatment and management, prevention and health promotion, as well as addressing the social determinants of health (SDoH) and a focus on redressing health inequities. We examined how Indigenous PHC mobilises and innovates during a public health crisis to address patient needs and the broader SDoH. A rapid review methodology conducted from January 2021 - March 2021 was purposefully chosen given the urgency with COVID-19, to understand the role of Indigenous PHC during a public health crisis. Our review identified five main themes that highlight the role of Indigenous PHC during a public health crisis: (1) development of culturally appropriate communication and education materials about vaccinations, infection prevention, and safety; (2) Indigenous-led approaches for the prevention of infection and promotion of health; (3) strengthening intergovernmental and interagency collaboration; (4) maintaining care continuity; and (5) addressing the SDoH. The findings highlight important considerations for mobilising Indigenous PHC services to meet the needs of Indigenous patients during a public health crisis such as the COVID-19 pandemic.


High-intensity swimming exercise reduces inflammatory pain in mice by activation of the endocannabinoid system.
As exercise intervention solely for pain reduction is relatively new, the available research still leaves an incomplete picture of responsible mechanisms and pathways. Nonetheless, evidence indicates that exercise-induced analgesia involves activation of the endocannabinoid (eCB) system. The present study investigated the role of the eCB system on the antihyperalgesic effect of high-intensity swimming exercise (HISE) in an animal model of peripheral persistent inflammation. Male Swiss mice were allocated to non-exercised and exercised groups and subjected to subcutaneous intraplantar injection (i.pl.) of a single dose of complete Freund's adjuvant (CFA) to induce inflammatory pain. Cumulative HISE was performed once a day, and mechanical hyperalgesia and edema were evaluated 0.5 hour after HISE for seven consecutive days. To investigate the role of the eCB system on the antihyperalgesic effect of HISE, non-exercised and exercised mice received intraperitoneal (ip), intrathecal (i.t.) or i.pl. injections of vehicle, AM281 (a CB1 cannabinoid receptor antagonist) or AM630 (a CB2 cannabinoid receptor antagonist) from the 3rd to 5th day after CFA injection. Mechanical hyperalgesia was evaluated 0.5 hour after HISE. In addition, the effect of the fatty acid amide hydrolase [FAAH] inhibitor or monoacylglycerol lipase [MAGL] inhibitor on the antihyperalgesic action of HISE was investigated. HISE reduced mechanical hyperalgesia with effects prevented by AM281 or AM630 pretreatment in all delivery routes tested. The inhibition of FAAH and MAGL prolonged the antihyperalgesic effect of HISE. These data demonstrate evidence for the role of the eCB system upon exercise-induced analgesia in a murine model of inflammatory pain.


Rectal biopsies: inaccuracy of histological grading in carcinoma of the rectum.
In a consecutive series of 70 patients with carcinoma of the rectum, 42 had operable tumours and in these the histology of the initial biopsy was compared with that of the excised specimen. In 9 of the 42 patients the histological grading of the original biopsy was different from that of the final specimen; in 3 the carcinoma was missed despite repeated preoperative biopsies; and in 5, errors were made in the diagnosis of carcinoma in polyps. In 5 of 7 cases of poorly differentiated carcinoma the initial biopsies indicated moderate differentiation: there was therefore a 70% inaccuracy in the preoperative diagnosis of poorly differentiated carcinoma of the rectum. The implications of this inaccuracy for the surgery of rectal cancer are discussed.


[Differential diagnosis of parapharyngeal tumors--the vagus neurinoma].
Among the tumours of the head and neck, only a small percentage is located in the parapharyngeal space. These are divided into salivary gland, neurogenic and so-called miscellaneous tumours. Two cases of vagus neurinoma are reported, and the diagnostic and therapeutic aspects are discussed. The neoplasms usually grow to a large size before they are treated, because they grow slowly and the signs and symptoms are non-specific. A latero-cervical approach is recommended for extirpation for diagnostic purposes.


Unique Contributions of Acceptance and Catastrophizing on Chronic Pain Adaptation.
Pain catastrophizing and acceptance represent distinct but interrelated constructs that influence adaptation to chronic pain. Clinical and laboratory research suggest that higher levels of catastrophizing and lower levels of acceptance predict worse functioning; however, findings have been mixed regarding which specific outcomes are associated with each construct. The current study evaluates these constructs in relation to pain, affect, and functioning in a treatment-seeking clinical sample. Participants included 249 adult patients who were admitted to an interdisciplinary chronic pain rehabilitation program and completed measures of pain and related psychological and physical functioning. Hierarchical multiple regression analyses indicated that pain catastrophizing and acceptance both significantly, but differentially, predicted depressive symptoms and pain-related negative affect. Only pain catastrophizing was a unique predictor of perceived pain severity, whereas acceptance uniquely predicted pain interference and performance in everyday living activities. There were no significant interactions between acceptance and catastrophizing, suggesting no moderation effects. Findings from the current study indicate a pattern of results similar to prior studies in which greater levels of catastrophic thinking is associated with higher perceived pain intensity whereas greater levels of acceptance relate to better functioning in activities despite chronic pain. However, in the current study, both acceptance and catastrophizing were associated with negative affect. These relationships were significant beyond the effects of clinical and demographic variables. These results support the role of pain acceptance as an important contribution to chronic pain-related outcomes alongside the well-established role of pain catastrophizing. Results are limited by reliance on self-report data, cross-sectional design, and low racial/ethnic diversity.


A holistic approach to promoting early child development: a cluster randomised trial of a group-based, multicomponent intervention in rural Bangladesh.
In low- and middle-income countries, children experience multiple risks for delayed development. We evaluated a multicomponent, group-based early child development intervention including behavioural recommendations on responsive stimulation, nutrition, water, sanitation, hygiene, mental health and lead exposure prevention. We conducted a 9-month, parallel, multiarm, cluster-randomised controlled trial in 31 rural villages in Kishoreganj District, Bangladesh. Villages were randomly allocated to: group sessions ('group'); alternating groups and home visits ('combined'); or a passive control arm. Sessions were delivered fortnightly by trained community members. The primary outcome was child stimulation (Family Care Indicators); the secondary outcome was child development (Ages and Stages Questionnaire Inventory, ASQi). Other outcomes included dietary diversity, latrine status, use of a child potty, handwashing infrastructure, caregiver mental health and knowledge of lead. Analyses were intention to treat. Data collectors were independent from implementers. In July-August 2017, 621 pregnant women and primary caregivers of children<15 months were enrolled (group n=160, combined n=160, control n=301). At endline, immediately following intervention completion (July-August 2018), 574 participants were assessed (group n=144, combined n=149, control n=281). Primary caregivers in both intervention arms participated in more play activities than control caregivers (age-adjusted means: group 4.22, 95% CI 3.97 to 4.47; combined 4.77, 4.60 to 4.96; control 3.24, 3.05 to 3.39), and provided a larger variety of play materials (age-adjusted means: group 3.63, 3.31 to 3.96; combined 3.81, 3.62 to 3.99; control 2.48, 2.34 to 2.59). Compared with the control arm, children in the group arm had higher total ASQi scores (adjusted mean difference in standardised scores: 0.39, 0.15 to 0.64), while in the combined arm scores were not significantly different from the control (0.25, -0.07 to 0.54). Our findings suggest that group-based, multicomponent interventions can be effective at improving child development outcomes in rural Bangladesh, and that they have the potential to be delivered at scale. The trial is registered in ISRCTN (ISRCTN16001234).


Ileus following spontaneous jejunum intramural hematoma: case report and review of the literature.
Anticoagulant therapy may cause the onset of a spontaneous intramural hematoma of the small bowel, in the jejunum, ileum or duodenum. A 53-year-old woman on therapy with heparin for previous pulmonary embolism was admitted for abdominal pain and vomit. Computed tomography scan visualized an intramural hematoma of the jejunum causing subtotal obstruction of the intestinal lumen. The patient underwent resection of a part of the jejunum, securing intestinal continuity by a mechanical side-to-side anastomosis. The postoperative course was regular, but the initial anticoagulant therapy was reduced to prevent recurrence. In conclusion, spontaneous hematoma of small bowel can occur as a complication of anticoagulant therapy. The clinical picture and rapid diagnosis indicate medical or surgical therapy.


The evaluation of haemodynamics in cirrhotic patients with spectral CT.
To evaluate haemodynamics in cirrhotic patients with portal hypertension using spectral CT imaging. 118 cirrhotic patients with portal hypertension were included in the study group (further divided into Child-Pugh A, B and C subgroups). The control group consisted of 21 subjects with normal liver functionality. All subjects underwent three-phase spectral CT scans. Material decomposition images with water and iodine as basis material pairs were reconstructed. The iodine concentrations for the hepatic parenchyma in both arterial and portal venous phases were measured. The arterial iodine fraction (AIF) was obtained by dividing the iodine concentration in the hepatic arterial phase by that in the portal venous phase. AIF values from the study and control groups were compared using analysis of variance and between subgroups using a post-hoc test with Bonferroni correction, with a statistical significance of p<0.05. The AIF was 0.25±0.05 in the control group, and 0.29±0.10, 0.37±0.12 and 0.43±0.14 in the study group with Child-Pugh Grades A, B and C, respectively. The difference in AIF between the control and study groups was statistically significant. The differences were statistically significant between the subgroups with multiple comparisons except between the control group and the Child-Pugh A group (p=0.685). AIF measured in spectral CT could be used to evaluate the liver haemodynamics of cirrhotic patients. The AIF, provided by spectral CT, could be used as a new parameter to observe liver haemodynamics.


[Salt sensitive blood pressure and the renin-angiotensin system in hypertension].
The relationship between (excessive) use of sodium chloride and the blood pressure is still equivocal. Blood pressure responses to alterations in dietary salt consumption vary greatly between individuals, which has led to the concept of salt sensitivity. Although the mechanisms which determine the degree of salt sensitivity are not fully understood, the renin-angiotensin system seems to play a key role. A relative inability of this system to respond promptly to alterations in salt intake may underlie the development of salt sensitivity. By administering drugs which block the renin-angiotensin system to patients with essential hypertension, blood pressure is rendered more sensitive to the effects of salt restriction and (or) diuretic treatment.


Androgen deprivation use with external beam radiation for prostate cancer: results from CaPSURE.
Recent data support the role of androgen deprivation in men undergoing external beam radiotherapy for prostate cancer. The benefits of neoadjuvant, concurrent or adjuvant treatment have been limited to men at intermediate and high risk. We examined the patterns and predictors of androgen deprivation in men undergoing external beam radiation therapy in CaPSURE. CaPSURE is an observational, longitudinal disease registry, from which 932 men met study inclusion criteria. Androgen deprivation was classified as neoadjuvant-within 9 months of radiation or adjuvant-from the start of radiation to 6 months after completion. Time trends in androgen deprivation as well factors associated with combined therapy were elucidated using multivariate analyses. In this study 40%, 39% and 21% of men could be categorized into high, intermediate and low risk groups, respectively. Overall 42% and 33% of patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. Between 1997 and 2002 neoadjuvant hormone use increased significantly in all risk groups, including patients at low risk. On multivariate analyses only the year of diagnosis and clinical risk group were associated with receiving androgen deprivation with radiation. A significant increase in combined androgen deprivation and external radiation was observed in the last decade in men with intermediate and high risk disease. Nevertheless, more widespread acceptance is necessary since a substantial minority continue to receive radiation alone. Many patients with low risk disease that is amenable to radiation monotherapy also receive androgen deprivation. No clinical or sociodemographic features predicted the use of androgen deprivation with external radiation.


Turning up a new pattern: Identification of cancer-associated fibroblast-related clusters in TNBC.
Growing evidence indicates a connection between cancer-associated fibroblasts (CAFs) and tumor microenvironment (TME) remodeling and tumor progression. Nevertheless, how patterns of CAFs impact TME and immunotherapy responsiveness in triple-negative breast cancer (TNBC) remains unclear. Here, we systematically investigate the relationship between TNBC progression and patterns of CAFs. By using unsupervised clustering methods in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset, we identified two distinct CAF-associated clusters that were related to clinical features, characteristics of TME, and prognosis of patients. Then, we established a CAF-related prognosis index (CPI) by the least absolute shrinkage and selection operator (LASSO)-Cox regression method. CPI showed prognostic accuracy in both training and validation cohorts (METABRIC, GSE96058, and GSE21653). Consequently, we constructed a nomogram with great predictive performance. Moreover, the CPI was verified to be correlated with the responsiveness of immunotherapy in three independent cohorts (GSE91061, GSE165252, and GSE173839). Taken together, the CPI might help us improve our recognition of the TME of TNBC, predict the prognosis of TNBC patients, and offer more immunotherapy strategies in the future.


An analysis of a puncture wound case with medical intervention.
A worker noted a small wound to his thumb when leaving a work site that was undergoing decontamination because of past operations with plutonium (Pu) and americium (Am). Direct surveys of the wound site confirmed the presence of contamination. The chelating agent Ca-DTPA was administered via a nebuliser within an hour after discovery of the wound. External measurements were made of the wound site and wound dressings; 24-h urinary excretion data were collected periodically and the Pu and Am urine content was determined. Zn-DTPA was administered on three occasions. The ICRP Pu systemic model was modified to consider the enhanced urinary excretion following administration of the chelating agents. The analysis indicated that the wound resulted in an initial deposition of 400 Bq 238Pu, 2240 Bq (239/240)Pu and 1060 Bq 241Am. About 70% of the initial wound activity was removed by surgical procedures and less than 1% of the wound activity was removed by chelation therapy. This paper compares the observed urinary excretion data with that indicated by a simulation of the kinetics of the transfer from the wound site and the kinetics of the chelating agent and Pu.


Reduction of C-peptide secretion in noninsulin-dependent diabetic patients with long duration of insulin treatment.
We examined the responses of serum free C-peptide immunoreactivity (CPR) during a 100 g oral glucose tolerance test (OGTT) on diabetic patients undergoing different kinds and durations of treatment. None of the patients were ketosis-prone or had any history of nephropathy and they all developed diabetes when over the age of 30. The sigma serum free CPR (the sum of serum free CPR values during OGTT) of group A (duration of insulin treatment was less than 5 years, N = 10) was found to be higher than that of group B (duration of insulin treatment was 5 years or more, N = 10) (p less than 0.005). On the other hand, the sigma serum free CPR of group C (treatment with an oral hypoglycemic agent for less than 5 years, N = 9) was not statistically different from that of group D (treatment with an oral hypoglycemic agent for 5 years or more, N = 11). There were no statistical differences between group A and group B in age at onset, duration of diabetes, daily insulin dose, relative body weight index, serum creatinine or sigma BG (the sum of blood glucose values during OGTT). Just before the start of insulin treatment, there were no significant differences between the two groups in the following: 1. fasting blood glucose values (all 10 patients measured in group A and 9 patients in group B) 2. blood glucose and plasma immunoreactive insulin (IRI) responses (7 patients measured in group A and 6 in group B). Among those with plasma IRI measured on the previous occasion, sigma serum free CPR was found to be higher in group A than in group B (p less than 0.025) at the time of the present study.(ABSTRACT TRUNCATED AT 250 WORDS)


Generation of fibrinolytic activity in bovine plasma by the combined effects of chloroform and dextran sulphate.
Bovine plasma yields fibrinolytically inactive euglobulin fractions, even when prepared in the presence of dextran sulphate. Addition of flufenamate to these solutions only occasionally elicits a slight activity. However, highly fibrinolytic solutions are produced when euglobulins precipitated in the presence of dextran sulphate are exposed to chloroform. Evidence indicates that a plasminogen activator is formed, which subsequently converts plasminogen present in the fractions to plasmin. Bovine euglobulin fractions contain an inhibitor which seems to be specifically directed towards urokinase and not to plasmin or to tissue plasminogen activator. Its inhibiting capacity is decreased after treatment with chloroform.


Influence of dietary inosine and vitamin C supplementation on growth, blood chemistry, oxidative stress, innate and adaptive immune responses of red sea bream, Pagrus major juvenile.
Both inosine (INO) and vitamin C (l-ascorbic acid, AsA) play important roles in growth performance, feed utilization and health status of fish. Therefore, a 56 days feeding trial was conducted to determine the interactive effects of dietary INO and AsA on growth performance, oxidative status, innate and adaptive immune responses of red sea bream. Fish growth performance and fed utilization parameters were significantly affected by dietary INO supplementation but not by AsA. Fish fed diets with INO at 4 g kg-1 diet in combination of high and low levels of AsA (3.1 g kg-1 and 9.3 g kg-1) produced the highest growth and feed utilization performances. In terms of growth and feed utilization performances no significant interaction effects were observed between INO and AsA. Dietary INO significantly influenced hematocrit, glucose and glutamyl oxaloacetic transaminase (GOT) content of red sea bream meanwhile AsA also significantly influenced hematocrit, glucose, total cholesterol, blood urea nitrogen (BUN) and glutamic-pyruvate transaminase (GPT) content of the test fish. No significant interaction effects was also observed between INO and AsA on measured hematological parameters. Reactive oxygen metabolites (d-ROMs) significantly influenced by both INO and AsA. Fish fed diet groups D1, D4 and D6 showed best oxidative stress resistance. Only INO was a significant factor on nitro-blue-tetrazolium activity (NBT) and bactericidal activity (BA). Neither INO nor AsA was a significant factor on serum catalase activity (CAT), total serum protein (TSP), peroxidase activity (PA) and lysozyme activity (LA). No significant interaction effects was observed between INO and AsA on measured innate immune parameters. Agglutination antibody titer was significantly influenced by dietary supplementation, after 15 days of vaccination but not in 21 days. In the day 15th fish and diet group D3 and D5 showed significantly higher values compared to diet groups control and D1. INO was the only significant factor of increasing agglutination antibody titer in 15 t h day. While AsA was not a significant factor on agglutination antibody titer values in day 15 t h, there was an interaction between dietary INO and AsA levels. Finally under the experimental conditions, fish fed high INO and low AsA levels (4 g kg-1 and 0.31 g kg-1 diet, respectively) showed best growth and feed utilization performance. Simultaneously, low level of INO and high level of AsA (2 g kg-1 and 0.93 g kg-1 diet, respectively) improved blood chemistry and immunological parameters. Furthermore, combined use of INO and AsA is possible to improve hemato-immunological responses of red sea bream.


Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy.
Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells.


Clinical Effectiveness of Lyme Vaccine: A Matched Case-Control Study.
We conducted a matched case-control study to assess the effectiveness of Lyme vaccine (LYMErix) as it was used in clinical practice. We found ≥3 doses to be 71% effective against Lyme disease. This is the first study to show that the Lyme vaccine is effective in a real-world setting.


Adrenoceptor expression and diurnal rhythms of melatonin and its precursors in the pineal gland of type 2 diabetic goto-kakizaki rats.
A decrease in the nighttime release of the pineal hormone melatonin is associated with aging and chronic diseases in animals an humans. Melatonin has a protective role in type 2 diabetes; however, its synthesis itself is affected in the disease. The aim of this study was to detect crucially impaired steps in the pineal melatonin synthesis of type 2 diabetic Goto-Kakizaki (GK) rats. Therefore, plasma melatonin concentrations and the pineal content of melatonin and its precursors (tryptophan, 5-hydroxytryptophan, serotonin, and N-acetylserotonin) were quantified in GK rats compared with Wistar rats (each group 8 and 50 wk old) in a diurnal manner (four animals per group and per time point). Additionally, the expression of pineal adrenoceptor subtype mRNA was investigated. We found that in diabetic GK rats, 1) inhibitory alpha-2-adrenoceptors are significantly more strongly expressed than in Wistar rats, 2) the formation of 5-hydroxytryptophan is crucially impaired, and 3) the pineal gland protein content is significantly reduced compared with that in Wistar rats. This is the first time that melatonin synthesis is examined in a type 2 diabetic rat model in a diurnal manner. The present data unveil several reasons for a reduced melatonin secretion in diabetic animals and present an important link in the interaction between melatonin and insulin.


Parasite transmission in a natural multihost-multiparasite community.
Understanding the transmission and dynamics of infectious diseases in natural communities requires understanding the extent to which the ecology, evolution and epidemiology of those diseases are shaped by alternative hosts. We performed laboratory experiments to test how parasite spillover affected traits associated with transmission in two co-occurring parasites: the bacterium Pasteuria ramosa and the fungus Metschnikowia bicuspidata Both parasites were capable of transmission from the reservoir host (Daphnia dentifera) to the spillover host (Ceriodaphnia dubia), but this occurred at a much higher rate for the fungus than the bacterium. We quantified transmission potential by combining information on parasite transmission and growth rate, and used this to compare parasite fitness in the two host species. For both parasites, transmission potential was lower in the spillover host. For the bacterium, virulence was higher in the spillover host. Transmission back to the original host was high for both parasites, with spillover influencing transmission rate of the fungus but not the bacterium. Thus, while inferior, the spillover host is not a dead-end for either parasite. Overall, our results demonstrate that the presence of multiple hosts in a community can have important consequences for disease transmission, and host and parasite fitness.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'.


Alterations in tissue glutathione and angiotensin converting enzyme due to inhalation of diesel engine exhaust.
Quantitative changes in reduced glutathione (GSH) and angiotensin converting enzyme (ACE) of lung and extrapulmonary tissues were determined following exposure of laboratory animals to diesel engine exhaust (DEE). Exposure of male rats and guinea pigs to DEE containing 750 micrograms particulates per cubic meter for 12 wk did not cause any changes in GSH levels of lung, liver, and heart compared to control values. Rats were then exposed for various time periods to 6 mg/m3 DEE. Two weeks of exposure produced statistically significant increases of 21 and 7% in GSH levels of lung and liver, respectively, but not change in the heart. Following 4 wk of exposure, lung showed a 14% increase and heart an 11% increase in GSH level. Furthermore, rats exposed for 4 wk to DEE did not show any particular susceptibility toward the GSH-depleting effect of acetaminophen as compared to controls. A significant depletion (15%) of hepatic GSH was observed after 8 wk of exposure, while lung was still showing an increase of 18% in GSH and heart was unaffected. Time-dependent increases of 18 and 33% in serum ACE activity were noted after 4 and 8 wk of exposure. Pulmonary ACE activity did not decrease until after 8 wk, and then to a small extent (7%). The observed increases in GSH may have been related to the presence of NO2 in the DEE. On the other hand, the depletion of hepatic GSH suggests production of electrophilic compounds due to an induction of metabolic activity of liver. The change in serum ACE activity may be due to time-requiring perturbations in the pulmonary endothelial cells.


Using ecological-niche modeling as a conservation tool for freshwater species: live-bearing fishes in central Mexico.
Ecological-niche modeling is an important tool for conservation assessment of terrestrial species; however, its applicability has been poorly explored in the aquatic realm. Goodeines are a monophyletic group of viviparous freshwater fishes that are well known in central Mexico, with 41 species in 19 genera. Given the number of threats to biodiversity in the region, goodeines represent an excellent model with which to test novel conservation approaches. We assessed the conservation status of the goodeines (37 species), based on their potential distributions predicted by ecological-niche models generated with the genetic algorithm for rule-set prediction (GARP). Predictions of species' distributions performed well in six out of eight species for which sufficient information was available to perform estimations of the area under the curve (AUC) in receiver operating characteristic plots. Extensive field surveys conducted in recent years in most cases confirm the models' predictions. Species richness exhibited a nested pattern, in which the number of species increased toward the center of the distribution of the group. At the basin level, the Río Ameca Basin had the highest number of species (11), chiefly because of the high number of microendemic species (6). Human activities within water bodies (e.g., extensive aquaculture) and drainages (e.g., agriculture, ranching, industrial activities) have affected most goodeines severely, given the deleterious effects of pollution and introductions of exotic species, such as carp (Cyprinus carpio, Ctenopharingodon idella) and tilapia (Oreochromis spp.). Our results paint a pessimistic picture for the long-term survival of many goodeines in their natural environment, and realistic conservation measures are complex and would require immediate protection of specific areas that we have identified. Ecological-niche modeling is a suitable tool for conservation assessment of freshwater species, but availability of environmental information on aquatic systems (e.g., temperature, water speed, pH, oxygen concentration) would improve distributional predictions.


N-terminal half of transportin SR2 interacts with HIV integrase.
The karyopherin transportin SR2 (TRN-SR2, TNPO3) is responsible for shuttling specific cargoes such as serine/arginine-rich splicing factors from the cytoplasm to the nucleus. This protein plays a key role in HIV infection by facilitating the nuclear import of the pre-integration complex (PIC) that contains the viral DNA as well as several cellular and HIV proteins, including the integrase. The process of nuclear import is considered to be the bottleneck of the viral replication cycle and therefore represents a promising target for anti-HIV drug design. Previous studies have demonstrated that the direct interaction between TRN-SR2 and HIV integrase predominantly involves the catalytic core domain (CCD) and the C-terminal domain (CTD) of the integrase. We aimed at providing a detailed molecular view of this interaction through a biochemical characterization of the respective protein complex. Size-exclusion chromatography was used to characterize the interaction of TRN-SR2 with a truncated variant of the HIV-1 integrase, including both the CCD and CTD. These experiments indicate that one TRN-SR2 molecule can specifically bind one CCD-CTD dimer. Next, the regions of the solenoid-like TRN-SR2 molecule that are involved in the interaction with integrase were identified using AlphaScreen binding assays, revealing that the integrase interacts with the N-terminal half of TRN-SR2 principally through the HEAT repeats 4, 10, and 11. Combining these results with small-angle X-ray scattering data for the complex of TRN-SR2 with truncated integrase, we propose a molecular model of the complex. We speculate that nuclear import of the PIC may proceed concurrently with the normal nuclear transport.


Surgery for obesity.
Bariatric surgery today is the only effective therapy for morbid obesity. Commonly performed procedures include adjustable gastric banding and vertical banded gastroplasty, variations of the Roux-en-Y gastric bypass, biliopancreatic diversion or duodenal switch, and mixed procedures. This review discusses key issues in the surgical management of morbid obesity. The two most common bariatric procedures performed worldwide are laparoscopic adjustable gastric banding and laparoscopic Roux-en-Y gastric bypass. Controversy exists regarding the best surgical procedure. Weight loss decreases according to the procedures performed in following decreasing order: biliopancreatic diversion, Roux-en-Y gastric bypass, vertical banded gastroplasty, adjustable gastric banding. Concerning the complications and quality of life, there is no single operation for morbid obesity without drawbacks. Cost-effectiveness analyses have demonstrated that bariatric surgery is cost effective at less than 50,000 US dollars/quality-adjusted life years. According to current opinion, gastric restrictive procedures (adjustable gastric banding, vertical banded gastroplasty) are generally considered safe and quick to perform, but the long-term outcome and quality of life have been questioned. By contrast, the long-term efficacy of adjustable gastric banding can be improved by the development of new band devices. More complex bariatric procedures, such as the Roux-en-Y gastric bypass or biliopancreatic diversion, have a greater potential for serious perioperative complications but are associated with good long-term outcome in terms of weight loss combined with less dietary restriction.


Quantitative Solid-State NMR Study on Ligand-Surface Interaction in Cysteine-Capped CdSe Magic-Sized Clusters.
Ligand-surface interaction of semiconductor nanoparticles (NPs) controls their optoelectronic properties, and thus examination of the interaction is essential for the nanoelectronic applications of NPs. Herein, solid-state nuclear magnetic resonance (NMR) is performed to unravel the ligand-surface interaction in cysteine-capped CdSe magic-sized clusters. 15N-113Cd through-bond J-filtered NMR directly shows the presence of the nitrogen-cadmium chemical bond for the first time and indicates that ∼43% of the amines form the chemical bond. 15N-113Cd through-space dipolar-correlated NMR reveals that ∼54% of the amines locate nearby the surface cadmium with the average nitrogen-cadmium distance of 0.247 nm. The average distance is comparable with that estimated by J-filtered NMR. The difference of the two ratios (∼11%) proposes that some amines locate on the surface without forming the chemical bond, and these amines affect the relatively long observed distance in the dipolar-based experiment. Our study shows effectiveness of solid-state NMR for investigation of the ligand-surface interactions of NPs.


Low-Loss Dielectric Ink for Printed Radio Frequency and Microwave Devices.
Direct write printing is restricted by the lack of dielectric materials that can be printed with high resolution and offer dissipation factors at radio frequency (RF) within the range of commercial RF laminates. Herein, we outline the development of dielectric materials with dielectric loss below 0.006 in X and Ku frequency bands (8.2-18 GHz), the range required for radio frequency and microwave applications. The described materials were designed for printability and processability, specifically a prolonged viscosity below 1000 cps and a robust cure procedure, which requires minimal heat treatment. In the first stage of this work, nonpolar ring-opening metathesis polymerization (ROMP) is demonstrated at room temperature in an open-air environment with a low-viscosity monomer, 5-vinyl-2-norbornene, using the second-generation Grubbs catalyst (G-II). Differential scanning calorimetry (DSC) was used to study how the catalyst activity is increased with heating at various stages in the reaction, which is then used as a strategy to cure the material after printing. The resulting cured poly(5-vinyl-2-norbornene) material is then characterized for dielectric and mechanical performance before and after a secondary heat treatment, which mimics processing procedures to incorporate subsequent printed conductor layers for multilayer applications. After the secondary heat treatment, the material exhibits a 55.0% reduction in the coefficient of thermal expansion (CTE), an increase in glass-transition temperature (Tg) from 32.4 to 46.1 °C, and an increased 25 °C storage modulus from 428 to 1031 MPa while demonstrating a minimal change in dielectric loss. Lastly, samples of the developed dielectric material are printed with silver overtop to demonstrate how the material can be effectively incorporated into fully printed, multilayer RF applications.


Peer support in health care and prevention: cultural, organizational, and dissemination issues.
As reviewed in the article by Perry and colleagues (2014) in this volume, ample evidence has documented the contributions of peer support (PS) to health, health care, and prevention. Building on that foundation, this article discusses characteristics, contexts, and dissemination of PS, including (a) fundamental aspects of the social support that is often central to it; (b) cultural influences and ways PS can be tailored to specific groups; (c) key features of PS and the importance of ongoing support and backup of peer supporters and other factors related to its success; (d) directions in which PS can be expanded beyond prevention and chronic disease management, such as in mental health or interventions to prevent rehospitalization; (e) other opportunities through the US Affordable Care Act, such as through patient-centered medical homes and chronic health homes; and (f) organizational and policy issues that will govern its dissemination. All these demonstrate the extent to which PS needs to reflect its contexts--intended audience, health problems, organizational and cultural settings--and, thus, the importance of dissemination policies that lead to flexible response to contexts rather than constraint by overly prescriptive guidelines.


Associations between cortical thickness and parasympathetic nervous system functioning during middle childhood.
Positive associations have been found between cortical thickness and measures of parasympathetic cardiac control (e.g., respiratory sinus arrhythmia, RSA) in adults, which may indicate mechanistic integration between neural and physiological indicators of stress regulation. However, it is unknown when in development this brain-body association arises and whether the direction of association and neuroanatomical localization vary across development. To investigate this, we collected structural magnetic resonance imaging and resting-state respiratory sinus arrhythmia data from children in middle childhood (N = 62, Mage = 10.09, range: 8.28-12.14 years). Whole-brain and exploratory ROI analyses revealed positive associations between RSA and cortical thickness in four frontal and parietal clusters in the left hemisphere and one cluster in the right. Exploratory ROI analyses revealed a similar positive association between cortical thickness and RSA, with two regions surviving multiple comparison correction, including the inferior frontal orbital gyrus and the Sylvian fissure. Prior work has identified these cortical areas as part of the central autonomic network that supports integrative regulation of stress response (e.g., autonomic, endocrine, and behavioral) and emotional expression. Our results suggest that the association between cortical thickness and resting RSA is present in middle childhood and is similar to the associations seen during adulthood. Future studies should investigate associations between RSA and cortical thickness among young children and adolescents.


Review: Genetic and genomic selection as a methane mitigation strategy in dairy cattle.
Over the last decade, extensive research effort has been placed on developing methane mitigation strategies in ruminants. Many disciplines on animal science disciplines have been involved, including nutrition and physiology, microbiology and genetic selection. To date, few of the suggested strategies have been implemented because: (1) methane emissions currently have no direct or indirect economic value for farmers, with no financial incentive to change practices and (2) most strategies have limited, or no, long-term effects. Consequently, there is a fundamental need for research on methane mitigation strategies across disciplines. Coordinated international initiatives similar to METHAGENE could represent highly relevant coordination tool of collaboration between countries, facilitating knowledge exchange, sharing concerns and building future collaborations.


A highly selective direct method of detecting sulphate-reducing bacteria in crude oil.
The aim of this work was to develop a highly selective method of detecting sulphate-reducing bacteria (SRB) in crude oil. A pair of PCR primers was designed based on an alignment of the nucleotide sequence of the 16S rRNA genes from the Desulfovibrionaceae family. DNA extraction from crude oil was performed by the method using zirconia beads and a stool kit. The PCR specifically detected Desulfovibrio and Desulfomicrobium in a sediment sample. When nucleic acids extracted directly from crude oil were used for the PCR, 16S rRNA genes of Desulfovibrio and Thermodesulforhabdus norvegicus were detected. IMPACT OF STUDY: A simple direct method for detection of the SRB in crude oil using PCR was established.


Immunomodulatory Effect of Lycium barbarum Polysaccharides against Liver Fibrosis Based on the Intelligent Medical Internet of Things.
Lycium barbarum polysaccharide (LBP) is the main active component of Lycium barbarum and has many beneficial effects, including neuroprotection, antiaging, and antioxidation. This study mainly explores the immunomodulatory effect of Lycium barbarum polysaccharides against liver fibrosis based on the intelligent medical Internet of Things. This measure emphasizes that the current effective methods and methods for the treatment of liver cancer are mainly combined treatments of Western medicine and Chinese medicine. These treatments have a certain effect in preventing liver cancer, reducing recurrence, and reducing side effects. Among them, chemotherapy has unique advantages in improving the quality of life and prolonging survival. With the development of medical science and technology, the clinical efficacy and efficacy of traditional Chinese medicine in the treatment of liver cancer are constantly improving. The mechanism is also studied from many aspects. The treatment time of LBPs on fibrotic hepatocytes was set to 24 h. Take liver fiber cells in logarithmic growth phase and incubate them at 37°C for 24 h. The whole process uses a temperature sensor for intelligent temperature control. In the experiment, groups of LBPs with different concentrations and different molecular weight ranges were set up and each group had 6 multiple holes. The original medium was aspirated and replaced with a medium containing different concentrations of LBPs (12.5, 25, 50, 100, and 200 μg/mL) and cultured for 24 h. Based on the previous research, this study used in vitro cell experiments, microscopic observation, and MTT method to verify whether Lycium barbarum polysaccharides inhibit the proliferation of human liver cancer cells in vitro and whether they cooperate with the chemotherapy drug fluorouracil to play a tumor-killing effect. Animal experiments, using ELISA, HE staining, and other methods, explore the molecular and immunological mechanisms of LBP's antiliver cancer effect from the perspective of Th/Th2 differentiation balance and DC function, in order to provide experimental evidence for Chinese medicine polysaccharides in cancer immunotherapy and application. At different LBP concentrations (0 μmol/L, 5 μmol/L, 10 μmol/L, and 15 μmol/L), the inhibition rates were 0.80%, 20.06%, 35.44%, and 55.39%, respectively. This study provides a new method for large-scale expansion of hepatocytes in vitro, laying a stronger foundation for biological treatment of liver fibrosis.


[Detection of numerical chromosome aberrations in urologic malignancies using in situ hybridization from formarin-fixed paraffin sections].
It has been shown that molecular cytogenetics in interphase nuclei is applicable to paraffin embedded sections from formarin-fixed materials utilizing in situ hybridization (ISH). This allows precise identification of numerical abnormalities of chromosome in tumor cells without disruption of tumor morphology. Thirteen cases of bladder cancer and twenty six cases of prostate adenocarcinoma were evaluated for numerical aberrations of chromosome 1, 7, 10, 11, 17, 18, X and Y utilizing biotinylated probes specific for the alpha satellite region. In two cases from total prostatectomy, one case from total cystectomy and two cases from TUR-P specimen, hybridized chromosomes could not be detected in individual tumor cells. With respect to the appearance of the ISH signal, optical concentration and time for the digestion enzyme has to be established essentially. This technique can now be applied on the detection of biological activity in various types of urological cancer.


An orexigenic role for mu-opioid receptors in the lateral parabrachial nucleus.
The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective mu-opioid receptor (mu-OR) agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 microl) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective mu-opioid antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the kappa-antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating mu-ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate mu-ORs in the LPBN in the normal regulation of food intake.


CHANGES IN ELECTRICAL CONDUCTANCE OF RHODOPSIN ON PHOTOLYSIS.
The change in electrical conductance of rhodopsin solutions was studied with flash-photolysis techniques. The whole pattern of the conductance change on illumination consists of three different processes: (I) the initial decrease, (II) the increase, and (III) the slow decrease, which are in decreasing order of reaction rate. The processes I, II, and III can be most distinctly recognized on flash illumination of acid, slightly acid, and alkaline rhodopsins, respectively. On the other hand, the bleaching of rhodopsin also shows at least three successive phases of different rates, but none of them corresponds in reaction rate to any of the processes of the conductance change. The conductance change may be related to conformational changes of opsin following photoisomerization of retinene, being due to hydrogen or hydroxyl ions and some other inorganic electrolytes. The amount of the change, especially the initial decrease, is proportional to the amount of rhodopsin bleached, even when the photochemical back reaction towards rhodopsin and isorhodopsin occurs in the chromophore depending on the intensity of illumination. Of the three processes, the slow decrease is most severely affected by aging, but the initial decrease and increase are slightly affected. These two processes promptly caused by illumination are connected closely to the conformational changes during the conversion of rhodopsin to metarhodopsin, and perhaps to the initial stage of excitation of rod cells.


Chromatin Immunoprecipitation and Sequencing (ChIP-seq) Optimized for Application in Caenorhabditis elegans.
Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) has become one of the most popular methods to study protein-DNA interactions and can be used, for instance, to identify the binding sites of transcription factors or to determine the distributions of histones with specific post-translational modifications throughout the genome. Although standard ChIP-seq protocols work well in most experimental systems, there are exceptions, and one of these is the popular model organism Caenorhabditis elegans. Even though this system is very amenable to genetic and cytological methods, biochemical approaches are challenging. This is due to both the animals' cuticle, which impairs lysis as well as penetration by cross-linkers, and the rather low protein and chromatin content per body weight. These issues have rendered standard ChIP-seq protocols inefficient in C. elegans and raised a need for their improvement. Here, we describe improved protocols, with the most important advances being the efficient breakage of the C. elegans cuticle by freeze-grinding and the use of a very sensitive sequencing library construction procedure, optimized for the relatively low DNA content per body weight of C. elegans. The protocols should therefore improve the reproducibility, sensitivity, and uniformity across tissues of ChIP-seq in this organism. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Growth and harvesting of synchronized Caenorhabditis elegans Basic Protocol 2: Chromatin immunoprecipitation (ChIP) Basic Protocol 3: Library construction for Illumina sequencing.


A Review of Gastric Cancer Research in Malaysia
Incidence rates of gastric cancer in Malaysia has declined by 48% among males and 31% among females in the latest reporting period of 13 years. Malays used to have age-standardized-rates only a fifth of those in Chinese and Indians, but the incidence among them is slightly rising even as the rates drop in the other races. Besides ethnicity, a low level of education, high intake of salted fish and vegetables, H pylori infection and smoking are risk factors. Consumption of fresh fruit and vegetable is protective. Variation in the strains of H pylori infection affect gastric cancer risk, with hspEAsia isolates among Chinese appearing linked to a high incidence than with hpAsia2 or hpEurope strains among Indians and Malays. It was reported in the 1980s that only about 3% of patients presented with early gastric cancer, but more encouraging rates reaching 27% with Stage 1 and 2 disease have been reported in the twenty-first century from leading centres. More tumours occur in the distal stomach except in Kelantan, where the incidence is low and main site is the cardia. Prompt endoscopy is advocated and open access, with direct referrals, to such services using a weighted scoring system should be more utilized. In view of the high rate of late disease laparoscopic staging unnecessary laparotomy needs to be avoided. Late presentation of gastric cancer however, is still predominant and the mortality to incidence ratio is relatively high. Besides seeking to reduce risk factors and achieve early detection, implementation of improved care for patients with late disease must be promoted in Malaysia.


Glycogen-Rich Clear Cell Squamous Cell Carcinoma Originating in the Oral Cavity.
Clear cell squamous cell carcinoma (CCSCC) is a rare histological subtype of squamous cell carcinoma (SCC) that was originally described in the skin. Here, we report a case of a 66-year-old female patient who presented with a fungating ulcerative mass of the left lateral tongue extending anteriorly to the floor of the mouth, and posteriorly to the left retromolar fossa and the oropharynx. The patient had a history of SCC of the left posterior tongue that was treated with partial glossectomy and adjuvant radiotherapy. Representative biopsies were obtained from the floor of the mouth, tongue and retromolar fossa. The examined biopsies showed various degrees of dysplastic surface epithelium with transition into infiltrating epithelial tumor nests and cords with clear cytoplasm and malignant cellular features. Pancytokeratin, CK5/6, and p63 were all diffusely positive. S-100, Calponin, and smooth muscle actin (SMA) were negative. PAS stain was diffusely positive and diastase labile in the tumor clear cells. Sparse areas of mucicarmine positivity were noted. Based on these findings a final diagnosis of a glycogen-rich CCSCC was given. This case represents a very rare histological variant of oral SCC, which is significant for the histological differential diagnosis of clear cell tumors of the oral cavity.


Preparation of medicinally active extracts and phytochemical characterisation of phytoconstituents from medicinal plants.
Medicinal plants contain many bioactive compounds that are often hosted in medicinally active extracts generated from their various parts. The quest for reliable products from medicinal plants escalated in recent years as an answer to emerging health complications and the much-needed sufficient scientific backing that is dependent on proper preparation and characterisation principles of active extracts. This study described the Soxhlet and the maceration methods that are used to process extracts from the inert materials of medicinal plants using appropriate biocompatible solvents, the phytochemical screening assays, and TLC, UV spectrometry, FT-IR, and GC-MS techniques used in phytochemical studies. These techniques are crucial in studies that are meant to explore the active components of medicinal plants and their relative pharmacological effects. This information can be used as a guide when formulating effective yet less toxic plant-derived drugs and provide opportunities to upgrade while reducing further complexity in phytochemical studies.


DNA, drugs and chariots: on a decade of pharmacogenomics at the US FDA.
Over the past 10 years, the US FDA has become a strong pharmacogenomics advocate as part of its mission to both protect and advance public health by enabling innovations that make medicines safer to use and more effective. The agency has evolved its advocacy cautiously on a foundation of science-based information from novel programs, such as the Voluntary Genomics Data Submission initiative, and on careful regulatory assessment of the extraordinary advances in clinical pharmacogenomics that have supported the update of drug labels with genetic information. This commentary goes into detail on the evolution of these achievements. However, many challenges remain for pharmacogenomics, and they will continue to evolve, and all stakeholders must work together. As the decade draws to a close, we have presented four major areas that need to be addressed collectively to assure that pharmacogenomics continues to mature over the next 10 years into a science that is essential to the practice of medicine.


[Incidence and mortality of massive transfusion in a university hospital: study of the period 2001-2005].
There are few epidemiological studies on massive transfusion (MT), although they may be important to evaluate possible strategies to reduce the number of transfused units, as well as transfusion side-effects. We, therefore, retrospectively assessed the incidence of MT at our institution (a 700-bed university hospital) during a 5-year period. Local blood bank records were searched for MT episodes occurred from January 2001 to December 2005. MT was defined as the transfusion of 8 or more packed red cell (PRC) units within 24 h. Patient's clinical data were exclusively gathered from the blood requesting form. Overall, 304 episodes of MT were identified in 288 patients (one episode per week), who received 4,845 PCR units (3,515 units within the first 24 h), because of ruptured aortic aneurism (n = 62), poly-trauma (n = 57), upper digestive bleeding (n = 51), cardiac surgery (n = 41), elective surgery (n = 36), emergency surgery (n = 30), and oncology surgery (n = 27). Mortality rate was 48%, and multivariate analysis identified age (odds ratio [OR] =1.023; 95% confidence interval [CI]. 1.006-1.040) and number of PRC transfused within the first 24 h (OR = 1.094; 95% CI, 1.0032-1.160) as weak but significant independent predictors of mortality, whereas poly-trauma diagnosis was a protective factor (OR = 0.325; 95% CI, 0.112 - 0,940). Overall, the mortality rate among patients receiving MT was very high, and was influenced by the number of transfused units, patient's age, and admitting diagnose. As the majority of the MT episodes occurred within the surgical or polytrauma context, possible strategies to reduce the volume of MT are discussed.


Frequency dependence and equilibration of the specific heat of glass-forming liquids.
We have performed molecular dynamics simulations on a glass-forming liquid consisting of a three-dimensional binary mixture of soft spheres. We show that a peak in the specific heat versus temperature can occur because a glassy system that shows no signs of aging progresses so slowly through the energy landscape that the minimum sampling time needed to obtain accurate thermodynamic averages exceeds the observation time. We develop a systematic technique to determine the equilibrium value of the specific heat and the minimum sampling time. Below the temperature of the specific heat peak, the minimum sampling time is orders of magnitude longer than the alpha relaxation time. We find that an equilibrium system that is not undergoing structural relaxation or aging has a frequency dependent specific heat that rises as the frequency decreases. The rise occurs at frequencies corresponding to periods that are long enough for the system to sample statistically independent energies. When the period is comparable to the minimum sampling time, the frequency dependent specific heat reaches a plateau. As a result, the specific heat has a frequency dependence at frequencies orders of magnitude lower than is implied by the inverse alpha relaxation time.


Endodontic Retreatment of Maxillary Second Molar with Four Roots.
The present communication describes the endodontic retreatment of a rare four-rooted maxillary second molar. A 25-year-old patient was referred to our dental practice requesting an apicoectomy because of continuous and permanent pain reaction six months after the first endodontic treatment. The sent radiograph demonstrated three filled root canals (one mesial, two distal) and four radiographically superimposing roots (two mesial, two distal). Due to the diagnosed chronic apical periodontitis and based on the visible untreated root canal, we decided to endodontically re-treat the quadrangular tooth against the referred apicoectomy. In the first session, only the previously untreated mesiopalatal root canal was mechanically prepared and filled with a corticosteroid- and tetracycline-containing paste. After two symptom-free weeks, the gutta-percha was removed from the other canals and calcium hydroxide was applied. Another two weeks later, the four root canals, whose orifices were "irregular quadrilateral" shaped on the pulp chamber floor representing Versiani Type A, were obturated. After the verification of this rare anatomy by cone beam computed tomography, the tooth was classified as Christie's radicular type II. One characteristic of this type is parallel running buccal and palatal roots, which caused a radiographic superimposition and probably led to the endodontic mistreatment in the first case.


MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine-cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein-protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.


Effects of pulsed electromagnetic field therapy on outcomes associated with osteoarthritis : A systematic review of systematic reviews.
Osteoarthritis (OA) is a chronic degenerative disease of multiple joints with a rising prevalence. Pulsed electromagnetic field (PEMF) therapy may provide a cost-effective, noninvasive, and safe therapeutic modality with growing popularity and use in physical medicine and rehabilitation. The purpose of this study was to synthesize the current knowledge on the use of PEMF in OA. A systematic review of systematic reviews was performed. The PubMed, Embase, PEDro and Web of Science databases were searched based on a predetermined protocol. Overall, 69 studies were identified. After removing the duplicates and then screening title, abstract and full text, 10 studies were included in the final analysis. All studies focused on knee OA, and four studies also reported on cervical, two on hand, and one on ankle OA. In terms of the level of evidence and bias, most studies were of low or medium quality. Most concurrence was observed for pain reduction, with other endpoints such as stiffness or physical function showing a greater variability in outcomes. The PEMF therapy appears to be effective in the short term to relieve pain and improve function in patients with OA. The existing studies used very heterogeneous treatment schemes, mostly with low sample sizes and suboptimal study designs, from which no sufficient proof of efficacy can be derived. A catalogue of measures to improve the quality of future studies has been drawn up.


Comparison of electrically and mechanically induced soleus H-reflex depression.
The aim of the present investigation was to compare the responses of mechanically-evoked and electrically-evoked conditioning among three different stimulus intensities and provide possible insight in determining whether these two types of inhibitory conditioning demonstrate the same response across the motor pool. The soleus H-reflex was tested under three different stimulus intensities (25% Hmax, 50% Hmax, and Hmax), and peak to peak amplitudes were recorded after either mechanical or electrical conditioning. For electrical conditioning, the ankle was held at 90 degrees, whereas mechanical conditioning utilized a 10 degree passive dorsiflexion at 15 degrees/sec back to the 90 degree position. All H-reflex measurements were recorded with the ankle at 90 degrees. A 3 x 2 (stimulus intensity x treatment condition) repeated measures ANOVA indicated significant main effects for stimulus intensity (FGG = 16.23; p = .003) and condition (FGG = 28.48; p < .001), as well as an interaction (F(2,18) = 6.59; p = .008). Simple main effects identified significantly more H-reflex depression for mechanical conditioning (94%, 91%, and 44%) compared to electrical conditioning (65%, 55%, and 19%) at 25% Hmax, 50% Hmax, and Hmax, respectively. There appears to be more mechanically than electrically stimulated H-reflex depression when testing at 25% Hmax, 50% Hmax, and Hmax. These results demonstrate the influence of Ia discharge properties on H-reflex depression and may suggest differences in the affinity of Ia terminals to intrinsic presynaptic inhibition at different stimulus intensities.


Lipopolysaccharide-induced alveolar epithelial permeability: the role of nitric oxide.
Intratracheal instillation of lipopolysaccharide (LPS) in the rat has been used as a model of acute lung inflammation. Among the early events in this process is a transient increase in airspace epithelial permeability which peaks 4 h after intratracheal instillation of LPS. The increased epithelial permeability is concomitant with the influx of neutrophils into the airspaces, peaking 8 h postinstillation. We have investigated the mechanism of this LPS-induced increase in epithelial permeability. The role of the neutrophil in LPS-induced epithelial permeability was assessed by pretreatment with neutrophil antibody to abolish neutrophil influx, which did not affect the increase in epithelial permeability. Because LPS instillation also induced increased tumor necrosis factor alpha (TNF-alpha) activity in bronchoalveolar lavage (BAL) fluid, and its release by cultured BAL leukocytes from treated animals, TNF-alpha antibody was coinstilled intratracheally with LPS in rats. TNF-alpha antibody eliminated TNF-alpha activity in BAL fluid, but had no effect on LPS-induced increased epithelial permeability. Increased levels of nitric oxide (NO), measured as nitrite, were also present in BAL fluid from LPS-treated rat lungs and LPS-elicited BAL leukocytes produced increased NO in culture. Treatment of rats with the specific NO synthase inhibitor L-NMMA significantly diminished the LPS-induced increased epithelial permeability. These data suggest that NO is involved in LPS-induced changes in epithelial integrity. However, other mechanisms should be evoked in addition to NO to explain completely the increased epithelial permeability produced by LPS.


Regulation of neural macroRNAs by the transcriptional repressor REST.
The essential transcriptional repressor REST (repressor element 1-silencing transcription factor) plays central roles in development and human disease by regulating a large cohort of neural genes. These have conventionally fallen into the class of known, protein-coding genes; recently, however, several noncoding microRNA genes were identified as REST targets. Given the widespread transcription of messenger RNA-like, noncoding RNAs ("macroRNAs"), some of which are functional and implicated in disease in mammalian genomes, we sought to determine whether this class of noncoding RNAs can also be regulated by REST. By applying a new, unbiased target gene annotation pipeline to computationally discovered REST binding sites, we find that 23% of mammalian REST genomic binding sites are within 10 kb of a macroRNA gene. These putative target genes were overlooked by previous studies. Focusing on a set of 18 candidate macroRNA targets from mouse, we experimentally demonstrate that two are regulated by REST in neural stem cells. Flanking protein-coding genes are, at most, weakly repressed, suggesting specific targeting of the macroRNAs by REST. Similar to the majority of known REST target genes, both of these macroRNAs are induced during nervous system development and have neurally restricted expression profiles in adult mouse. We observe a similar phenomenon in human: the DiGeorge syndrome-associated noncoding RNA, DGCR5, is repressed by REST through a proximal upstream binding site. Therefore neural macroRNAs represent an additional component of the REST regulatory network. These macroRNAs are new candidates for understanding the role of REST in neuronal development, neurodegeneration, and cancer.


High-power terahertz-wave generation using DAST crystal and detection using mid-infrared powermeter.
The exact power output of a table-top-sized terahertz (THz)-wave source using a nonlinear optical process has not been clarified because detectors for these experiments [Si bolometer, deuterated triglycine sulfate (DTGS), etc.] are not calibrated well. On the other hand, powermeters for the mid-infrared (mid-IR) region are well established and calibrated. We constructed a high-power dual-wavelength optical parametric oscillator with two KTP crystals as a light source for difference frequency generation. The obtained powers of dual waves were 21 mJ at ~1300 nm, ten times higher than that of the previous measurement. The device provides high-power THz-wave generation with ~100 times greater output power than that reported in previous works. A well-calibrated mid-IR powermeter at ~27 THz detected the generated THz wave; its measured energy was 2.4 microJ. Although the powermeter had no sensitivity in the lower-frequency range (below 20 THz), the pulse energy at such a low-frequency region was estimated in reference to the output spectrum obtained using a DTGS detector: the energy would be from about the submicrojoule level to a few microjoules in the THz-wave region.


Use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in context of COVID-19 outbreak: a retrospective analysis.
The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on antihypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P = 0.46), ICU admission (20% vs. 28%, P = 0.37) or invasive mechanical ventilation (18% vs. 26%, P = 0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.


Childhood food allergy and food allergen sensitisation are associated with adult airways disease: A birth cohort study.
Childhood food allergy (FA) and food allergen sensitization (FAS) are associated with allergic airway disease(s) [AAD] (asthma and rhinitis) in childhood. However, the associations between childhood FA/FAS and AAD in adulthood are not well described. We investigated the longitudinal relationship between childhood FA/FAS to common food allergens and AAD at 18 and 26 years, in the Isle of Wight birth cohort. Study subjects (N = 1456) were followed up at fixed time points from ages 1-26 years for FA/FAS status. AAD were evaluated from 4 years onwards. The associations between FA/FAS and AAD were assessed with univariate analyses and then multivariable logistic regression, adjusting for clinically relevant co-variates. Food allergy at 4 years was significantly associated with asthma at 18 years [adjusted odds ratio (aOR): 2.75, 95% CI: 1.53-4.92, p = .001] and 26 years (aOR: 2.62, 95% CI: 1.32-5.20, p = .006). Conversely, childhood FA was not associated with adulthood rhinitis whatsoever. While FAS at ages 4 and 10 were associated with both AAD, the associations between FAS and rhinitis were less robust relative to asthma. Childhood FA increased the odds of asthma during adulthood by nearly threefold. Additionally, childhood FAS was also associated with increased odds of asthma in adulthood. Conversely, FAS but not FA in childhood was associated with rhinitis in adulthood. We suggest that children with FA/FAS should be followed up to facilitate early detection and intervention of subsequent AAD, particularly asthma.


Age-related responses of skeletal muscle after ectopic innervation, with particular reference to 16S acetylcholinesterase, in adult rats.
The formation of ectopic junctions between the foreign fibular nerve and the soleus muscle of young (35-day-old) and mature (200-day-old) adult rats was induced by severing the normal nerve 4 weeks after implanting the foreign nerve. The various molecular forms of acetylcholinesterase (AChE) were studied both at the implanted region and at the original denervated endplates. The velocity of contraction was also studied. In young rats the 16S form was first detected in the ectopic junctions around day 5 after reinnervation; this form rapidly increased during the following weeks, reaching a plateau by day 20. By contrast, in mature rats the appearance of the 16S AChE was dramatically delayed; in fact, it could not be observed before day 80 after reinnervation. (The 16S AChE form appeared at day 20 after reinnervation in the original denervated endplates of young rats; however, at the same time, no effect was observed in mature animals.) The original, slow muscle fibers of the soleus became faster upon reinnervation; this change occurred also much earlier in younger than in mature rats. Our results indicate a loss of plasticity in the skeletal muscle of mature rats. We suggest caution in the use of the ectopic innervation model to study development in mature adult rats.


Relaxation times and modes of disturbed aggregate distribution in micellar solutions with fusion and fission of micelles.
We have performed direct numerical calculations of the kinetics of relaxation in the system of surfactant spherical micelles under joint action of the molecular mechanism with capture and emission of individual surfactant molecules by molecular aggregates and the mechanism of fusion and fission of the aggregates. As a basis, we have taken the difference equations of aggregation and fragmentation in the form of the generalized kinetic Smoluchowski equations for aggregate concentrations. The calculations have been made with using the droplet model of molecular surfactant aggregates and two modified Smoluchowski models for the coefficients of aggregate-monomer and aggregate-aggregate fusions which take into account the effects of the aggregate size and presence of hydrophobic spots on the aggregate surface. A full set of relaxation times and corresponding relaxation modes for nonequilibrium aggregate distribution in the aggregation number has been found. The dependencies of these relaxation times and modes on the total concentration of surfactant in the solution and the special parameter controlling the probability of fusion in collisions of micelles with other micelles have been studied.