Identification and subgrouping of pigeon type Newcastle disease virus strains by restriction enzyme cleavage site analysis.
A host variant of Newcastle disease virus (NDV, genus Avulavirus, family Paramyxoviridae) is responsible for an autonomous disease in pigeons. It emerged in the late 1970s in the Mediterranean region. Despite great genetic diversity the vast majority of strains belong to a monophyletic group (sublineage VIb) within genotype VI of NDV strains that were indigenous in the region at that time. To date only a monoclonal antibody assay is available for the specific identification of pigeon type strains. A specific genetic assay is described suitable for the identification of pigeon isolates. Cleavage site analysis of a 1349 bp amplicon of the fusion protein gene was carried out using restriction enzymes (RE) HinfI, BstOI and RsaI. RE analysis of over 100 strains isolated between 1978 and 2002 deriving from 16 countries has revealed nine RE-patterns, which were progressive site variants of the parental (group VI) genotype. In spite of substantial site variation, extant pigeon viruses lacked a BstOI cleavage site at nucleotide 1601 shared by other NDV strains of chicken origin. RE analysis is a simple and reliable method both for the identification and subgrouping of pigeon type viruses.


[Presence of potentially pathogenic bacteria and fungi in the cooling-lubricating emulsion used in the aluminum sheet rolling process].
Microbiological tests of aluminium rolling water-oil emulsion reveal high level of contamination: relatively anaerobic bacteria 10(6)-10(8) cells/ml, fungi and yeasts 10(3)-10(4) cells/ml, and also anaerobic bacteria Desulfovibrie sp. reducing sulfates to hydrogen sulfide. In emulsion samples there were present bacterial strains potentially dangerous to health, belonging to the family Enterobacteriaceae, Vibrionaceae, Pseudomonadaceae, Bacillaceae. The fungi and yeasts found in the emulsion were identified as: Aspergillus sp., Penicillium sp., Cladosporium sp., Cephalosporium sp., Candida sp. The emulsion sprayed in aerosol in air of the mill was the infecting source for the workers. The emulsion was protected by a biocid and thus the growth of potentially pathogenic microorganisms was inhibited.


Measuring the invisible: perinatal health outcomes of unregistered women giving birth in Belgium, a population-based study.
The unregistered population remains under-researched because of its "invisible" status in statistics. Studies on perinatal health outcomes of unregistered women remains particularly limited. Our objectives were 1) to describe the sociodemographic profiles of women who are not legally residing in Belgium and 2) to analyze the associations of registration status with pregnancy outcomes according to socioeconomic status and nationality. We analysed data from birth and death certificates taken from the Belgian civil registration system, linked with the National Population Registry (NPR). The data relates to all singleton babies born between 2010 and 2016 (n = 871,283), independent of their mother's NPR registration status. We used logistic regression to estimate the odds ratios for the associations between perinatal outcomes (perinatal mortality, prematurity and low birth weight) and maternal NPR registration status according to socioeconomic status and maternal nationality. Over the study period, 1.9% of births were to mothers without NPR-registration. Unregistered women from newer EU member states and non-European countries were particularly disadvantaged from a socioeconomic point of view. Apart from women with a South American nationality, all other groups of unregistered women had higher rates of prematurity, low birth weight, and perinatal mortality, compared to registered mothers (p < 0.0001). Unregistered women from Belgium and EU15 nationalities had particularly higher rates of prematurity, low birth weight, and perinatal mortality, compared to registered mothers, even after adjustment for socioeconomic status (p < 0.0001). The excess of perinatal mortality for non-European unregistered mothers could partly be explained by their precarious socioeconomic situation. This is the first study to include data on mothers who were not legally residing in Belgium. Unregistered women giving birth in Belgium are likely a heterogeneous socioeconomic group. Overall, unregistered women have increased risks of adverse perinatal outcomes, but it is likely that the causal mechanisms differ starkly between Belgian, European and non-European women. Further research is needed to understand the mechanisms behind these accrued rates. It is important to keep measuring the health outcomes of the populations which are "invisible" in national statistics, in order to identify the groups in most need of integration and access to services.


Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries.
Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD. Clinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Transcriptome analysis was performed using AltAnalyze. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups. Placental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Transcriptomic and histologic analysis demonstrates reduced cell activity and nutrient transport capability in HLHS but not TGA placentas which appear to increase/maintain these mechanisms. Despite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the disparities in birthweights frequently seen between these CHD subtypes, in contrast our transcriptomic and histologic analyses reveal differentially regulated mechanisms between the subtypes that may explain these disparities.


Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population.
Oxidized LDL (oxLDL) is thought to play a key role in the inflammatory response in the arterial vessel wall. In a prospective, nested, case-control study, the association between plasma oxLDL and risk of an acute coronary heart disease (CHD) event was investigated in men without prevalent CHD or diabetes mellitus at baseline. Subjects came from 2 population-based MONICA/KORA Augsburg surveys conducted in the years 1989-1990 and 1994-1995 with follow-up in 1998 (mean+/-SD follow-up time, 5.6+/-2.6 years). OxLDL was determined by ELISA in 88 men with incident CHD and in 258 age- and survey-matched controls. Hazard ratios (HRs) were estimated from conditional logistic-regression models with matching for age and survey. Baseline mean plasma oxLDL concentrations were significantly higher in subjects who subsequently experienced an event compared with controls (mean+/-SD, 110+/-32 versus 93+/-28 U/L; P< or =0.001). After adjustment for smoking, hypertension, obesity, physical activity, education, and alcohol consumption, the HR for a future CHD event in a comparison of the upper tertile of the oxLDL distribution with the lower tertile was 4.25 (95% confidence interval, 2.09 to 8.63; P<0.001). Plasma oxLDL was the strongest predictor of CHD events compared with a conventional lipoprotein profile and other traditional risk factors for CHD. When both oxLDL and C-reactive protein were simultaneously assessed in the same model, they still predicted future CHD events even after multivariable adjustment. Elevated concentrations of oxLDL are predictive of future CHD events in apparently healthy men. Thus, oxLDL may represent a promising risk marker for clinical CHD complications and should be evaluated in further studies.


In Vitro Susceptibility Testing of Clinical Isolates of Chlamydia trachomatis.
Penicillin class antibiotics have demonstrated varying degrees of in vivo and in vitro success when tested against Chlamydia trachomatis. The activity of ampicillin-sulbactam, an agent commonly utilized in the treatment of pelvic infections, was tested to ascertain if any antichlamydial activity is present. Up to six endocervical isolates of C. trachomatis were tested against each of five antibiotics including doxycycline, erythromycin, clindamycin, ampicillin/sulbactam, and sulbactam alone. McCoy cell monolayers were inoculated with high inclusion counts of 10,000-30,000 inclusion-forming units (IFU) per coverslip, and exposed to each antibiotic. Up to nine subsequent antibiotic free culture passes were performed to assess the viability of abnormal inclusions. Doxycycline, erythromycin, and clindamycin achieved 100% eradication of inclusions at concentrations of 4.0, 2.0, and 1.0 microg/mL. Exposure to ampicillin/sulbactam resulted in a greater than 99% reduction in the inclusion count at 32.0 microg/mL, while sulbactam by itself demonstrated considerably less activity. Abnormal inclusions were noted only in the ampicillin/sulbactam exposed cells, and these, plus all inclusions remaining following sublethal exposure to the other antibiotics, resulted in regrowth to control levels in subsequent passes. Doxycycline and erythromycin demonstrated excellent activity. Clindamycin and ampicillin/sulbactam also significantly reduced inclusion formation, and therefore may provide adequate C. trachomatis coverage in patients receiving these antibiotics for pelvic infections.


Selective Turn-On Fluorescence Sensing of Cyanide Using the Pyridoxal Platform of a Ni(II) Complex.
Cyanide is a very toxic pollutant to aquatic life and the environment. Analytical methods for the quantitative assay of cyanide, which are rapid, sensitive (low limit of detection), and cost-effective, are in great demand. Colorimetric and fluorometric methods are ideally suited for this purpose. In this report, we describe a Ni(II) complex containing a pyridoxal platform for the rapid and sensitive fluorometric estimation of cyanide. The square-planar Ni(II) complex, [Ni(L)(N3)]·3H2O, where the ligand LH = 4-[(2-dimethylamino-ethylimino)-methyl]-5-hydroxymtheyl-2-methyl-pyridin-3-ol, a Schiff base formed between pyridoxal and (2-dimethylamino)ethyl amine, was synthesized and characterized by various spectroscopic techniques as well as by single-crystal X-ray structure determination. The complex was found to selectively bind CN- in the presence of other biologically important anions such as F-, Cl-, Br-, I-, OAc-, S2-, NO3 -, PO4 3-, SO4 2-, and H2PO4 - in tris-HCl/NaCl buffer [pH = 7.4], and it can be monitored by fluorescence turn-on or by UV-visible spectroscopy. The binding constant of the complex with CN- was estimated to be 2.046 × 1014 M-2 and the limit of detection (LOD) was 9 nM, the LOD being considerably lower than the maximum permissible level of cyanide ions (1.9 μM) in drinking water, as recognized by the World Health Organization (WHO). The effects of pH and temperature on the sensing are also investigated. The Ni(II) complex is also found to bind to calf-thymus DNA very strongly, and the apparent binding constant (K app) was determined to be 1.33 × 107 M-1 by the fluorescence quenching of the ethidium bromide-DNA adduct by the complex.


Effect of androgen excess and glucocorticoid exposure on metabolic risk profiles in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Data on cardiovascular morbidity in adults with congenital adrenal hyperplasia (CAH) is sparse. We therefore aimed to determine the role of androgen control and glucocorticoid therapy on metabolic health. For that purpose, we included 90 patients (N = 39 men, N = 51 women) with classic CAH due to 21-hydroxylase deficiency (N = 61 salt wasting, N = 29 simple virilizing) and an equal number of controls matched for age, sex, BMI and smoking-habits. We could show that there was no difference in intima-media-thickness between patients and controls and only one patient fulfilled all criteria of the metabolic syndrome. CAH men presented with an increased relative body fat mass in comparison to controls (25.6 % vs. 22.1 %; p = 0.011) while this was not true for CAH women. Body fat was lower in those taking hydrocortisone instead of synthetic glucocorticoids (B = -3.27; p = 0.048). While arterial hypertension was rare, 54 % of patients had an impaired systolic drop at night or were classified as non-dippers (17 %). Impaired dipping was not associated with evening glucocorticoid and fludrocortisone intake but mediated by sodium levels. Insulin resistance was more common in CAH women (B = 1.689; p = 0.036) and in those with poor androgen control (B = 0.823; p = 0.046). In summary, we could show that good cardiovascular health outcome in adult CAH patients can be achieved. Hydrocortisone is superior in terms of body composition. It is yet unclear how non-dipping will translate into cardiovascular morbidity in the long-term.


The state of neutral lipids in normal and cataractous human lenses.
A simple and rapid high pressure liquid chromatographic method (HPLC) was developed to analyse the neutral lipid fraction from normal and cataractous human lenses. No differences were found between old normal and cataractous lenses suggesting that membrane deterioration in cataracts is not due to oxidation of these components. Several new lens components were isolated and identified including cholesterol metabolites, and vitamin E (alpha-tocopherol).


The role of antioxidants in the era of cardio‑oncology.
Although most chemotherapeutic drugs have the potential to exert cardiotoxicity, these drugs have been chosen for use in cancer treatment because survival and curability benefits outweigh the risk of these complications. Anthracyclines, for example, are a powerful class of chemotherapeutic agents; however, their use is restricted by dose-related cardiotoxicity. Experimental evidence strongly supports the role of reactive oxygen species in this process, suggesting that antioxidants may be effective in protecting the heart from toxicity. Clinical use of antioxidants to protect the heart during anthracycline chemotherapy has been controversial due to the potential for reduced cytotoxic efficacy toward cancer cells. Results from randomized clinical trials addressing whether antioxidants either reduce the incidence of clinical heart failure among patients undergoing anthracycline-based chemotherapy or reduce the response rates to anthracycline-based chemotherapy have been unclear. While anthracyclines are by far the most well-studied antitumor agents with cardiotoxic properties, evidence now shows that reactive oxygen species may play roles in cardiotoxicity induced by other chemotherapeutic agents such as cyclophosphamide, cisplatin, 5-fluorouracil, and trastuzumab. Thus, in the new era of combination therapy and long-term survival of cancer patients, the use of antioxidants to support cancer therapy should be revisited.


Exploring the patient experience of digital ulcers in systemic sclerosis.
Digital ulcers are common in patients with systemic sclerosis, affecting over half of patients during the course of their disease. For some patients, digital ulcers occur as isolated phenomena; whereas, for others, digital ulceration is recurrent, and often refractory to intervention. Demonstrating treatment efficacy for digital ulcer disease has typically focussed on clinician opinion of ulcer healing and new ulcer occurrence. Advances in management have improved outcomes which may have had the unfortunate effect of rendering traditional trial endpoints less effective at demonstrating treatment efficacy. Despite recent improvements in management, our work is not complete and digital ulceration remains a major cause of morbidity for many patients with systemic sclerosis. This review shall examine the patient experience of digital ulcers in systemic sclerosis. We shall consider how a detailed understanding of the severity and burden of digital ulceration, aetiopathogenesis, and their impact on emotional health, function, work and social participation might inform the development of novel clinical trial outcomes that can support future advances in the assessment and management of digital ulceration in systemic sclerosis.


Relapsing Neurological Complications in a Child With ATP1A3 Gene Mutation and Influenza Infection: A Case Report.
Mutations in the ATP1A3 gene encoding the α3 subunit of Na+/K+-ATPase are associated with different neurological manifestations that may be elicited by febrile episodes. A recently described phenotype, linked to the p.Arg756Cys mutation, is clinically characterized by Relapsing Encephalopathy with Cerebellar Ataxia (RECA). In our case, a diagnosis of RECA has been established, and despite an alternative, reasonable cause had been already identified. We describe the case of a child with two recurrent episodes, 2 years apart, of hypotonia and ataxia. In both episodes, a laboratory-confirmed influenza virus infection suggested the diagnosis of influenza-associated encephalopathy. After the second episode, a search for genetic mutations was performed, and ATP1A3 mutation associated to RECA was found. After both episodes, the child was discharged after partial improvement of neurological conditions. The diagnosis of encephalopathy in children is often challenging. A genetic predisposition to neurological decompensation should be suspected in case of recurrent episodes, even if an alternative diagnosis has been established. Indeed, febrile infections may only represent the trigger of neurological involvement. In these patients, the knowledge of a genetic predisposing factors may help in the prevention of neurological episodes by the prompt use of anti-pyrectics and preventive measures as appropriate vaccination.


Asymmetric Diels-Alder reactions of chiral cyclopropylidene imide dienophiles: preparation of gem-dimethyl- and spirocyclopropane norbornyl carboxylic acids.
A highly efficient strategy has been developed for the rapid asymmetric synthesis of gem-dimethyl and spirocyclopropyl norbornyl carboxylic acids. The key transformation involved the unprecedented asymmetric Diels-Alder reaction of highly reactive beta,beta-cyclopropyl-alpha,beta-unstaturated N-acyloxazolidinones with cyclopentadiene affording the adducts in high yield and de.


The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis.
To examine the relationship between hepatotoxic risk factors and liver histopathology in patients with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). We graded the histology of 33 percutaneous liver biopsy specimens from 25 patients with JRA treated at Children's Hospital Medical Center, Cincinnati, Ohio, using the Roenigk Classification Scale. Stepwise linear and logistic regression analyses were performed to examine the relationship of the Roenigk grade and presence of liver fibrosis of biopsy specimens with potential risk factors. Twenty-seven biopsy specimens (82%) were classified as grade I, 4 (12%) as grade II, and 2 (6%) as grade IIIA; none demonstrated significant fibrosis. The frequency of biochemical abnormalities (P <.001) and body mass index (P =.05) were the only risk factors found to significantly relate to the Roenigk grade. The following factors were not significantly associated with the Roenigk grade: age, gender, disease duration, JRA subtype and course, duration of MTX administration, weekly MTX dose, cumulative dose of MTX, route of MTX administration, use of folic acid supplementation, concurrent use of other medications, and potential hepatotoxic comorbidities. Serial biochemical abnormalities are significantly associated with Roenigk grade and the presence of liver fibrosis. These findings concur with studies of patients with rheumatoid arthritis, suggesting that guidelines for monitoring MTX hepatotoxicity in rheumatoid arthritis may be applicable to patients with JRA.


RCN1 suppresses ER stress-induced apoptosis via calcium homeostasis and PERK-CHOP signaling.
Endoplasmic reticulum (ER) stress is caused by the disturbance of ER homeostasis and leads to the activation of the unfolded protein response (UPR), which alleviates stress at an early stage and triggers apoptosis if homeostasis fails over a prolonged timeframe. Here, we report that reticulocalbin 1 (RCN1), a member of the CREC family, is transactivated by nuclear factor kappa B (NF-κB) during ER stress and inhibits ER stress-induced apoptosis. The depletion of RCN1 increases the UPR during drug-induced ER stress by activating PRKR-like ER kinase-CCAAT/enhancer-binding protein-homologous protein (PERK-CHOP) signaling, thus inducing apoptosis. Furthermore, we found that the first two EF-hand calcium-binding motifs of RCN1 specifically interact with inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1) on loop 3 of its ER luminal domain and inhibit ER calcium release and apoptosis. Together, these data indicate that RCN1, a target of NF-κB, suppresses ER calcium release by binding to IP3R1 and decreases the UPR, thereby inhibiting ER stress-induced apoptosis.


Production in vitro by spinal cord of growth factor(s) acting on newt limb regeneration: influence of regeneration of the nerve fibers.
In order to approach the problem of regulation of growth factor(s) production during limb regeneration in newt, we co-cultivated spinal cord segments and blastemas. First we showed that, like the sensory supply, the spinal cord possesses size-dependent mitogenic capacities for limb blastemas. A 5-mm long spinal segment enhances radiolabelled thymidine incorporation to the same extent as spinal ganglia (1.6-fold). Second, we co-cultivated blastemas with spinal segments, the nerve fibers of which were previously stimulated to regenerate (= stimulated spinal segment) or not (= non-stimulated spinal segment). Only after a 24-h coculture, do stimulated spinal segments enhance thymidine incorporation in blastemas 2-fold more than non-stimulated spinal segments. Our results suggest that during limb regeneration brachial nerves produce more growth factor(s) when regrowing, inducing the proliferation of blastema cells which in return deliver a neuronotrophic factor acting on these nerves.


A bird brain's view of auditory processing and perception.
By studying the primary forebrain auditory area of songbirds, field L, using a song-inspired synthetic stimulus and reverse correlation techniques, we found a surprisingly systematic organization of this area, with nearly all neurons narrowly tuned along the spectral dimension, the temporal dimension, or both; there were virtually no strongly orientation-sensitive cells, and in the areas that we recorded, cells broadly tuned in both time and frequency were rare. In addition, cells responsive to fast temporal frequencies predominated only in the field L input layer, suggesting that neurons with fast and slow responses are concentrated in different regions. Together with other songbird data and work from chicks and mammals, these findings suggest that sampling a range of temporal and spectral modulations, rather than orientation in time-frequency space, is the organizing principle of forebrain auditory sensitivity. We then examined the role of these acoustic parameters important to field L organization in a behavioral task. Birds' categorization of songs fell off rapidly when songs were altered in frequency, but, despite the temporal sensitivity of field L neurons, the same birds generalized well to songs that were significantly changed in timing. These behavioral data point out that we cannot assume that animals use the information present in particular neurons without specifically testing perception.


Effects of propylthiouracil (PTU) on the immunological status of the chicken.
Effects of propylthiouracil (PTU) using different treatment schedules on immune functions in young male chicken were studied. Antibody productions to sheep red blood cells (SRBC) and Brucella abortus (BA) were found to rise in the chicks treated with 0.1% and 1% PTU. Furthermore, the chicks treated with 1% PTU exhibited a significantly greater reaction to phytohemagglutinin (PHA) in skin test using the wing web than the control did. Treatment of 5% PTU, however, inhibited the antibody productions to SRBC and BA and the reaction for the skin test to PHA. Antibody titers to both antigens and serum IgG level were lower in the chicks after cessation of PTU treatment. The most conspicuous histology was the lymphatic depletion of the lymphoid organs in chicks treated with 5% PTU. The bursa of Fabricius, thymus and spleen were severely atrophied. The total WBC and the number of lymphocytes and monocytes were significantly reduced in the presence of 0.1% and 1% PTU at 8 weeks of age. Although, concentrations of serum thyroxin (T4) and 3,5,3'-triiodothyronine (T3) were significantly lower in the chicks treated with all doses of PTU, the cessation of the treatment was followed by an increase in the concentrations of serum T4 and T3 to levels not different from in the untreated control chicks. These data showed that PTU at 0.1% and 1% concentrations did not suppress immune responses in chickens unlike the case reported in mammals.


A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain.
Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics. A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months. Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5-9 days) and mean time of viremia was 6.8 days (range 3-9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted. We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing. NCT02372175.


[Changes in the corticosterone content in the blood plasma of inbred mice after stress exposure].
The open field test was used for examination of the corticosterone level in the blood plasma of inbred mice with different responsiveness to stress situation. The initial level of the hormone in C57B1/6 mice was higher than that in CBA or BALB/c mice. The data indicate the interstrain differences in the hormone change to stress.


Three-Dimensional Analysis of the Pharyngeal Airway Volume and Craniofacial Morphology in Patients With Bilateral Cleft Lip and Palate.
This study aimed to determine the correlations between the craniofacial morphology and pharyngeal airway volume in patients with complete bilateral cleft lip and palate (BCLP). Retrospective study. Tertiary hospital. Twenty-seven patients with complete BCLP and 27 class I control patients, aged 10 to 14 years. The pharyngeal airway volume and craniofacial morphology were evaluated using cone-beam computed tomography. Measurements were compared between groups and any correlations were identified. A significantly smaller total pharyngeal airway volume (TPV), oropharyngeal airway volume, and upper (UOPV) and lower (LOPV) oropharyngeal airway volume were found in patients with BCLP than in class I control patients, with no difference in the nasopharyngeal volume between groups. Furthermore, the craniofacial morphology measurements of N-Me, S-Go, Or-C, Ptm-C, Me-C, Co-Go, Go-Me, Ptm-Or, N-S-Ar, and Ar-Go-Me significantly differed between the BCLP and control groups (all P < .05). Multiple regression analysis indicated that Ptm-C and Me-C; Ptm-C, Or-C, and Me-C; and Me-C explained 20.3%, 38.9%, and 17.1% of the variations in TPV (P = .025), UOPV (P = .002), and LOPV (P = .018), respectively. Total pharyngeal airway volume, TPV, OPV, UOPV, and LOPV were significantly smaller in patients with BCLP than in class I controls. In patients with BCLP, the maxilla showed inhibited sagittal development and a retrograde position; moreover, the pharyngeal airway volume was weakly associated with the position of the maxilla and mandible relative to the coronal plane.


The effect of continuous positive airway pressure on total antioxidant capacity in obstructive sleep apnea: a systematic review and meta-analysis.
Obstructive sleep apnea (OSA), a sleep-related disorder with high prevalence, is associated with an imbalance in oxidative stress and is linked to cardiovascular disease. There are conflicting reports regarding the effectiveness of continuous positive airway pressure (CPAP) therapy on oxidative stress/antioxidant markers in patients with OSA. This review was performed to evaluate the influence of therapy with CPAP on serum/plasma total antioxidant capacity (TAC) in patients with OSA. The Cochrane Library, Web of Science, Scopus, Embase, and PubMed were searched through June 2022 to obtain studies evaluating CPAP treatment on TAC in patients with OSA. Overall results were tested using standardized mean difference (SMD) with a 95% confidence interval (CI). Comprehensive Meta-Analysis V2 software was employed to perform analyses. Ten studies with 12 effect sizes were eligible for inclusion in this analysis. The overall SMD revealed that CPAP therapy significantly increased TAC [SMD 0.497; 95% CI: 0.21 to 0.77; p: 0.00] in OSA. Analyses based on subgroups showed that the effect of CPAP therapy was significant in all subgroups according to therapy duration, age, BMI, and AHI. Whereas the meta-regression results indicated that the impact of therapy with CPAP on TAC is associated with AHI, BMI, and age in patients with OSA. The finding of this meta-analysis demonstrated a favorable impact of CPAP therapy on TAC levels in patients suffering from OSA.


Guidelines for appropriate in-hospital emergency team time management: the Brooke Army Medical Center approach.
Successful outcome following cardiac arrest have been reported in the range of 13-59%. It is well established that the time from the onset of a ventricular arrhythmia to successful defibrillation predicts outcome. Recent out of hospital arrest protocols minimizing time to defibrillation have reported significant improvement in outcomes. The Bethesda conference and American Heart Association (AHA) both set standards for defibrillation time for in hospital codes but do not set standards for other interventions. In February 2000, the Brooke Army Medical Center (BAMC) cardiopulmonary resuscitation committee published time guidelines for the initiation of CPR, emergency team arrival, first defibrillation and first medication. We sought to evaluate resuscitation outcomes before and after this intervention. Data on each response time was prospectively collected as was etiology for the event, emergency location, patient age, gender, and emergency outcome for the 7 months prior to the guideline introduction and 15 months afterwards. The mean response times (in minutes) for initiation of CPR (1.3 vs. 0.4), emergency team arrival (1.6 vs. 1.2), first defibrillation (7.8 vs. 6.6) and first medication (4.1 vs. 3.8) demonstrated trends toward improvement. Compliance with the time standards also increased (67-91, 85-95, 67-71 and 93-86%, respectively). Emergency survival trended toward improvement (47 vs. 57%) while discharge survival significantly increased from 3 to 24% (P=0.017). Setting time guidelines for Advanced Cardiac Life Support (ACLS) improved initiation of CPR, emergency team arrival, first defibrillation, and first medication administration. These time reductions were accompanied by improved event survival and a statistically improved survival to discharge.


Herpes zoster at the NIH: a 20 year experience.
One hundred and seven cases of herpes zoster in a hospitalized population with a variety of illnesses during a 20 year period were reviewed. Zoster occurred throughout the year, without seasonal predominance, and was most frequent in lymphoproliferative malignancy. In the majority, lesions were confined to the skin in one or more adjacent dermatomes (localized zoster) and were most frequent in the thoracic region. In 15 per cent of the cases, cutaneous dissemination of the lesions developed; this occurred four to 11 days after the onset of dermatomal lesions, and in one-third of these there was central nervous system involvement. Dissemination of zoster, however, directly resulted in only one death. Predisposing factors for zoster included local irradiation and, occasionally, surgery in subsequently involved areas. There were trends for more frequent splenectomies in patients with Hodgkin's disease in whom zoster subsequently developed, and for more frequent corticosteroid therapy in patiens with disseminated zoster. Advanced stage of Hodgkin's disease, in itself, was not associated with development of zoster, and the onset of zoster did not herald a poor prognosis for the underlying disease. Herpes zoster was, thus, largely a source of increased morbidity rather than mortality in the population studied, and multiple factors appeared to predispose to the development of zoster in this group of patients.


Effects of sustained administration of quetiapine alone and in combination with a serotonin reuptake inhibitor on norepinephrine and serotonin transmission.
Quetiapine is now used in the treatment of unipolar and bipolar disorders, both alone and in combination with other medications. In the current study, the sustained administration of quetiapine and N-Desalkyl quetiapine (NQuet) in rats in a 3 : 1 mixture (hQuetiapine (hQuet)) was used to mimic quetiapine exposure in patients because rats do not produce the latter important metabolite of quetiapine. Sustained administration of hQuet for 2 and 14 days, respectively, significantly enhanced the firing rate of norepinephrine (NE) neurons by blocking the cell body α₂-adrenergic autoreceptors on NE neurons, whether it was given alone or with a serotonin (5-HT) reuptake inhibitor. The 14-day regimen of hQuet enhanced the tonic activation of postsynaptic α₂- but not α₁-adrenergic receptors in the hippocampus. This increase in NE transmission was attributable to increased firing of NE neurons, the inhibition of NE reuptake by NQuet, and the attenuated function of terminal α₂-adrenergic receptors on NE terminals. Sustained administration of hQuet for 2 and 14 days, respectively, significantly inhibited the firing rate of 5-HT, whether it was given alone or with a 5-HT reuptake inhibitor, because of the blockade of excitatory α₁-adrenergic receptors on 5-HT neurons. Nevertheless, the 14-day regimen of hQuet enhanced the tonic activation of postsynaptic 5-HT(1A) receptors in the hippocampus. This increase in 5-HT transmission was attributable to the attenuated inhibitory function of the α₂-adrenergic receptors on 5-HT terminals and possibly to direct 5-HT(1A) receptor agonism by NQuet. The enhancement of NE and 5-HT transmission by hQuet may contribute to its antidepressant action in mood disorders.


21-Hydroxypregna-1,4-diene-3,11,20-trione: a biliary metabolite of a cartilaginous fish, Raja sp.
21-Hydroxypregna-1,4-diene-3,11,20-trione was isolated from skate bile and as an in vivo metabolite of 3H-1alpha-hydroxycorticosterone. Identity was established by chromatography and derivatization to constant 3H/14C ratio and mass spectrometry of the 20,21-acetonide. The new steroid was present in the free form and as the glucuronoside.


Development of the immune system in human fetal liver.
Fetal liver is a major site of development of the human immune system. Pre-B and B-lymphocytes are present in the human fetal liver at 12 weeks in a random distribution and increase with gestation. Most fetal liver cells are pre-B but mature B-cells are also present. Functional assays and transplantation experiments indicate that these B-cells are functional and can transfer immunologic memory, albeit imperfectly, in fetal liver reconstituted recipients. T-cell development, in contrast, occurs predominantly in the thymus. Progenitors of T-cells are present in fetal liver and can restore T-cell immunity in irradiated recipients. Human fetal liver contains 1-2% mature T-cells; functional assays are likewise negative. NK cells have been detected in human fetal liver at low frequency. Fetal liver also contains non-T, non-B cells capable of suppressing the development of alloantigen reactive T-cells; these have been termed veto cells. In summary, human fetal liver contains progenitors of several types of lymphoid cells and is an important site of immune development. It also may play a role in the induction of self tolerance during maturation of the immune system. These features of fetal liver may have important implications for the success of fetal liver transplantation in man.


Induced Pluripotent-stem-cell Related Genes Contribute to De-differentiation in Oral Squamous Cell Carcinoma.
Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4. Conversely, oncogenic transformations frequently express transcriptional factors and Nanog. Therefore, cancer cells present some similarities with induced pluripotent stem (iPS) cells. We investigated the expression of iPS-related genes in vitro and in clinical samples to identify their relationships with hypoxia and tumorigenesis. Oral squamous cell carcinoma (SCC) cells were used to show that expression levels of Oct3/4, Sox2, and Nanog were significantly increased in hypoxic condition in vitro and in moderately- and poorly-differentiated samples. We propose that Oct3/4, Sox2 and Nanog are associated with tumor hypoxia characterized in oral SCC and that these factors may also contribute to the undifferentiated potency observed in oral SCC clinically.


Clinical comparison of overlapping deletions of 19p13.3.
We present three patients with overlapping interstitial deletions of 19p13.3 identified by high resolution SNP microarray analysis. All three had a similar phenotype characterized by intellectual disability or developmental delay, structural heart abnormalities, large head relative to height and weight or macrocephaly, and minor facial anomalies. Deletion sizes ranged from 792 Kb to 1.0 Mb and included a common region arr [hg19] 19p13.3 (3,814,392-4,136,989), containing eight genes: ZFR2, ATCAY, NMRK2, DAPK3, EEF2, PIAS4, ZBTB7A, MAP2K2, and two non-coding RNA's MIR637 and SNORDU37. The patient phenotypes were compared with three previous single patient reports with similar interstitial 19p13.3 deletions and six additional patients from the DECIPHER and ISCA databases to determine if a common haploinsufficient phenotype for the region can be established.


Push-pull perfusion of pentylenetetrazol in the brain stem of 'encéphale isolé' cats.
Nine 'encéphale isolé' cats had 'push-pull' perfusions of pentylenetetrazol (PTZ) in various loci of the brain stem, while the EEG from the right and left motor cortices, EMG from neck muscles, ocular movements and clinical changes were recorded. Perfusions in the rostral MRF induced bilateral rhythmic paroxysmal EEG discharges and myoclonic twitching of neck and head, more prominent in the muscles contralateral to the perfused side. PTZ in the caudal MRF induced tonic-clonic paroxysmal EEG discharges and EMG seizures, similar to those seen when PTZ is injected systemically. Perfusion in the PRF induced EEG spindle bursts, muscular hypotonia and myosis. When perfusion in the MRF inducing rhythmic paroxysmal EEG discharges and myoclonic twitching was followed by perfusion in the PRF, the EEG discharges were not modified, but the myoclonic movements were abolished. Perfusions outside the MRF and PRF did not produce obvious changes other than tonic gaze deviation to the contralateral side or nystagmus. The results suggest that PTZ has a differential effect in various structures of the CNS, producing primary generalized convulsive seizures when acting directly on the MRF.


The European structural and investment funds and public investment in the EU countries.
Public investment is low and has declined in many EU countries since the global financial crisis. This paper estimates the effects of the various European Structural and Investment Funds (ESIF) on public investment in the EU countries. The analysis is run on annual data from 2000 to 2018 using dynamic panel data specifications. Funding from the Cohesion Fund, the EU's facility for its less developed members, has had an almost one-to-one effect on public investment in the short term, and more in the longer term. Funding from the European Regional Development Fund may have had some effect, but it cannot be estimated precisely. Funding from other ESIF funds does not seem to have been related to public investment in the EU countries.


Galanin- but not galanin-like peptide-containing axon terminals innervate hypophysiotropic TRH-synthesizing neurons in the hypothalamic paraventricular nucleus.
Galanin and galanin-like peptide (GALP) are both orexigenic peptides involved in the regulation of food intake and energy metabolism. To determine whether these peptides may directly influence the hypophysiotropic thyrotropin-releasing hormone (TRH)-synthesizing neurons, double-labeling immunocytochemistry was performed at light and electron microscopic levels using antisera against proTRH, galanin and GALP. Galanin-IR axons densely innervated all of the major parvocellular subdivisions of the PVN where proTRH neurons were identified. The periventricular and anterior parvocellular subdivisions exhibited a prominent network of galaninergic nerve fibers, while the density of fibers was less intense in the medial parvocellular subdivision. Galanin-immunoreactive (IR) axon varicosities were juxtaposed to the majority of TRH-synthesizing neurons in the anterior, medial and periventricular subdivisions of the PVN. Ultrastucturally, galanin-IR nerve terminals established symmetric type synapses with the perikarya of proTRH-IR neurons, suggesting an inhibitory nature of these contacts. In contrast, GALP immunoreactive fibers and nerve terminals concentrated primarily in the anterior parvocellular subdivision of the PVN and were found in association with only few proTRH-IR neurons in the periventricular and medial parvocellular subdivisions. In conclusion, the dense innervation of TRH neurons in all subdivisions of the PVN by galanin-IR axons indicates that galanin may be involved in the central regulation of the hypothalamic-pituitary-thyroid axis. In contrast, the relative paucity of GALP-containing axons in juxtapsoition to TRH neurons in the medial and periventricular parvocellular subdivisions of the PVN, the origin of hypophysiotropic TRH neurons, makes it unlikely that GALP similarly exerts direct regulatory effects on hypophysiotropic TRH neurons.


Human papillomavirus type distribution among heterosexual couples.
To gain a better understanding of human papillomavirus (HPV) transmission dynamics between sexual partners, HPV-type-specific concordance was investigated. Twenty-nine couples were enrolled in this cross-sectional study. Mean age was 30.5 years (range = 19.1-42.6 y) for men and 28.2 years (range = 19.4-44.5 y) for women. Samples were collected at the glans penis, penile shaft, and scrotum in men and at the endo/ectocervix and labia/vulva, and perineum in women. Samples were analyzed for the presence of HPV DNA first by polymerase chain reaction and then genotyped using the reverse-line blot method. Human papillomavirus prevalence for any HPV type was 75.9% among men and 86.2% among women. Eleven men and 10 women were infected with multiple HPV types. At least partial type-specific concordance was observed in 66% of the couples. Forty-one percent of the couples had perfect concordance. In 11 couples (37.9%), complete discordance was observed. These results provide valuable information about HPV-type-specific concordance and demonstrate the complexity of transmission dynamics in heterosexual couples.


Comparison of the phaco chop and drill-and-crack techniques for phacoemulsification of hard cataracts: A fellow eye study.
To quantify the intraoperative parameters and postoperative outcomes after using the phaco chop technique in one eye and drill-and-crack technique in the other eye in patients with bilateral dense brunescent cataract. The Lens Opacities Classification System III grading system was used to select 132 eyes of 66 patients with bilateral nuclear opalescence (NO) grade NO4 or grade NO5. One eye in each patient with bilateral dense brunescent cataract was subjected to phacoemulsification using the phaco chop technique, while the other eye was subjected to phacoemulsification with the drill-and-crack technique for nucleus disassembly. The intraoperative parameters were quantified. Surgical outcome was assessed preoperatively and 1 day, 4 weeks and 12 weeks postoperatively, and the outcomes of the two techniques were compared. There was no significant difference between the techniques in operative parameters [cumulative dissipated energy (p = 0.74), surgical time (p = 0.68) or surgical difficulty during nucleus disassembly (p = 0.80)]. There was no significant difference in the postoperative change in central corneal thickness between the techniques at day 1, 4 weeks and 12 weeks or in corneal endothelial cell density loss at 4 and 12 weeks (p > 0.05). There was no significant difference between the techniques in the mean corrected distance visual acuity (logarithm of the minimum angle resolution) at 4 weeks postoperatively (p = 0.25). The phaco chop and drill-and-crack techniques are equally effective for disassembly of hard NO4 and NO5 cataracts.


Mechanosensation: Too Hard or Too Soft?
Maternal decisions, such as where to build a nest or where to lay your eggs, are critical for the offspring's fitness and survival in any species. A new study in Drosophila now reveals that distinct classes of mechanosensory receptors and neurons fine tune the physical assessment of an oviposition site and determine where the female fly lays her eggs.


A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV.
We describe a new variant of Bernard-Soulier syndrome characterized by almost normal amounts of GPIb and severely reduced GPIX and GPV. Despite surface expression, GPIbalpha failed to support ristocetin-induced platelet agglutination and to bind two conformation-dependent monoclonal antibodies, suggesting a qualitative defect. Sequence analysis of the gene coding for GPIX revealed a T-to-C substitution at base 1811, leading to a Leu40Pro conversion, whereas no defects were found in the coding region of the GPIbalpha gene. Allele-specific restriction enzyme analysis showed that the propositus and one of his sisters. both with severe bleeding diathesis. were homozygous for the GPIX mutation: the members of the family with mild bleeding diathesis and/or giant platelets in the peripheral blood were heterozygous, whereas the healthy ones were homozygous for the normal allele. Infusion of 1-desamino-8-D-arginine vasopressin normalized bleeding time in the two severely affected patients, although it did not modify ristocetin-induced platelet agglutination or membrane expression of GPIbalpha, GPIX, GPIIb-IIIa and GMP-140. Moreover, in one patient, normalization of bleeding time and rise of von Willebrand factor plasma concentration did not seem to be directly related.


Effects of melittin on production performance, antioxidant function, immune function, heat shock protein, intestinal morphology, and cecal microbiota in heat-stressed quails.
The purpose of this study was to investigate the effects of melittin on production performance, antioxidant function, immune function, heat shock protein, intestinal morphology, and cecal microbiota of heat-stressed quails. A total of 120 (30-day-old) male quails were randomly divided into 3 groups. Each group consisted of 4 replicates with 10 birds per replicate. The ambient temperature of the control group (group W) was 24°C ± 2°C. The heat stress group (group WH) and the heat stress + melittin group (group WHA2) were subjected to heat stress for 4 h from 12:00 to 16:00 every day, and the temperature was 36°C ± 2°C for 10 d. The results showed that compared with the group W, heat stress significantly decreased growth performance, serum and liver antioxidative function, immune function, intestinal villus height (VH) and villus height-to-crypt depth ratio (VH/CD), and cecal microbiota Chao and ACE index (P < 0.05). The crypt depth (CD) in the small intestine, and HSP70 and HSP90 mRNA levels in the heart, liver, spleen, and kidney were significantly increased (P < 0.05). Dietary melittin significantly increased growth performance, serum and liver antioxidative function, immune function, intestinal VH and VH/CD, and cecal microbiota Shannon index in heat-stressed quails (P < 0.05). Melittin significantly decreased small intestinal CD, and HSP70 and HSP90 mRNA levels in the viscera (P < 0.05). Furthermore, dietary melittin could have balanced the disorder of cecal microbiota caused by heat stress and increased the abundance and diversity of beneficial microbiota (e.g., Firmicutes were significantly increased). PICRUSt2 functional prediction revealed that most of the KEGG pathways with differential abundance caused by high temperature were related to metabolism, and melittin could have restored them close to normal levels. Spearman correlation analysis showed that the beneficial intestinal bacteria Anaerotruncus, Bacteroidales_S24-7_group_norank, Lachnospiraceae_unclassified, Shuttleworthia, and Ruminococcaceae_UCG-014 increased by melittin were positively correlated with average daily feed intake, the average daily gain, serum and liver superoxide dismutase, IgG, IgA, bursa of Fabricius index, and ileum VH and VH/CD. In sum, our results demonstrate for the first time that dietary melittin could improve the adverse effects of heat stress on antioxidant function, immune function, heat shock protein, intestinal morphology, and cecal microbiota in quails, consequently improving their production performance under heat stress.


Lymph node retrieval and examination during the implementation of extended lymph node dissection for gastric cancer in a non-specialized western institution.
The optimal degree of lymph node dissection for gastric cancer is still matter of debate. Particularly, there are serious doubts about the reproducibility of extended lymph node dissection in western surgical units, and no studies to date have investigated factors influencing lymph node retrieval and examination during the learning curve. Univariate and multivariate retrospective analysis of 21 variables were carried out on a prospective series of 313 consecutive resections for gastric cancer performed by ten different surgeons, with lymph node retrieval and analysis performed by ten different pathologists. Endpoints were number of examined lymph nodes per patient, number of cases with inadequate nodal staging (<15 examined lymph nodes) and lymph node ratio (calculated as the absolute ratio between the number of metastatic and the number of examined lymph nodes). The number of examined lymph nodes per patient (mean ± SD 28.3 ± 14.1, median 26, range 2-78) was independently influenced by age, pN status, the type of gastric resection, the degree of lymph node dissection and single pathologist. There were 47 cases (15.0%) with incomplete nodal staging that was independently determined by the degree of lymph node dissection and by the pathologist. Lymph node ratio was independently influenced by the number of metastatic lymph nodes, the disease stage and by the histological subtype of the tumor. The role of an experienced or dedicated pathologist should not be underevaluated in western series when dealing with lymph node retrieval and examination. Lymph node ratio appeared not to be significantly influenced by the number of examined lymph nodes, being independently influenced only by the number of metastatic lymph nodes, the disease stage and by the histological subtype of the tumor. It could be therefore tested as a prognostic factor limiting the stage-migration phenomenon induced by extended lymph node dissection.


Leveling Up: A Review of Machine Learning Models in the Cardiac ICU.
Machine learning has emerged as a significant tool to augment the medical decision-making process. Studies have steadily accrued detailing algorithms and models designed using machine learning to predict and anticipate pathologic states. The cardiac intensive care unit is an area where anticipation is crucial in the division between life and death. In this paper, we aim to review important studies describing the utility of machine learning algorithms to describe the future of artificial intelligence in the cardiac intensive care unit, especially in regards to the prediction of successful ventilatory weaning, acute respiratory distress syndrome, arrhythmia, and acute kidney injury.


Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.
For several days after antigenic stimulation, human cytolytic T lymphocyte (CTL) clones exhibit a decrease in their effector activity and in their binding to human leukocyte antigen (HLA)-peptide tetramers. We observed that, when in this state, CTLs lose the colocalization of the T cell receptor (TCR) and CD8. Effector function and TCR-CD8 colocalization were restored with galectin disaccharide ligands, suggesting that the binding of TCR to galectin plays a role in the distancing of TCR from CD8. These findings appear to be applicable in vivo, as TCR was observed to be distant from CD8 on human tumor-infiltrating lymphocytes, which were anergic. These lymphocytes recovered effector functions and TCR-CD8 colocalization after ex vivo treatment with galectin disaccharide ligands. The separation of TCR and CD8 molecules could be one major mechanism of anergy in tumors and other chronic stimulation conditions.


Evaluation of a rapid, sensitive and specific assay for the determination of collagenolytic activity in biological samples.
Several methods for the determination of collagenolytic activity were compared from the point of view of sensitivity, selectivity, simplicity and practical value for large numbers of biological samples. A labelled collagen substrate was prepared using [3H]acetic anhydride. The specificity of the assay as well as conditions allowing an optimum detection limit were investigated. The influence of low temperatures, lyophilisation and salt concentration on Clostridium histolyticum collagenase have been investigated.


Noninvasive, wearable, and tunable electromagnetic multisensing system for continuous glucose monitoring, mimicking vasculature anatomy.
Painless, needle-free, and continuous glucose monitoring sensors are needed to enhance the life quality of diabetic patients. To that extent, we propose a first-of-its-kind, highly sensitive, noninvasive continuous glycemic monitoring wearable multisensor system. The proposed sensors are validated on serum, animal tissues, and animal models of diabetes and in a clinical setting. The noninvasive measurement results during human trials reported high correlation (>0.9) between the system's physical parameters and blood glucose levels, without any time lag. The accurate real-time responses of the sensors are attributed to their unique vasculature anatomy-inspired tunable electromagnetic topologies. These wearable apparels wirelessly sense hypo- to hyperglycemic variations with high fidelity. These components are designed to simultaneously target multiple body locations, which opens the door for the development of a closed-loop artificial pancreas.


Effect of arsenic trioxide on uveal melanoma cell proliferation in vitro.
The aim of this study was to investigate the effect of arsenic trioxide (ATO) on the growth of cultured uveal melanoma cells (OCM-1 cell line). Cultured OCM-1 cells were treated with 0.75-24 microM of ATO for 4-96 h. Cell viability was evaluated with the methylthiazoletetrazolium (MTT) assay as proliferation test. Apoptotic and necrotic cells were quantified using flow cytometry following Annexin-V/PI double stain. The cell morphology alteration was examined by light and electron transmission microscopy. To investigate the underlying mechanism of ATO-induced apoptosis and necrosis, glutathione peroxidase activity was measured, and mitochondrial membrane potentials were quantified using confocal microscopy. In the MTT assays, OCM-1 cell growth was inhibited at ATO concentrations of 1.5-24 microM. The 50% inhibitory concentration of ATO was 16.8 microM. At ATO concentrations of 12 and 24 microM, apoptosis and necrosis were induced after 24 h of incubation as shown by light and transmission electron microscopy. At ATO concentrations of 12 and 24 microM, the glutathione peroxidase activity was significantly (p < 0.05) reduced after 24 h of incubation, and the mitochondrial membrane potentials were significantly (p < 0.01) decreased after 4, 12 and 24 h of incubation. ATO inhibited ocular melanoma cell line growth at concentrations of 1.5-24 microM of ATO in a dose- and time-dependent manner by inducing apoptosis and necrosis of the tumor cells. The concurringly decreased glutathione peroxidase activity and the reduced mitochondrial membrane potentials may be possible underlying mechanisms for the apoptosis and necrosis of the tumor cells.


Enthusiasm, evidence and ethics: the triple E of minimally invasive pediatric surgery.
Minimally invasive techniques are applicable in more than 60% of abdominal and thoracic operations in children. Enthusiasts promoted these techniques for many years. However, level 1 evidence on advantages of minimally invasive surgery in children remains limited. Randomized controlled trials have been conducted for some types of procedures such as laparoscopic appendectomy, fundoplication, pyloromyotomy, and inguinal hernia repair. The results of these studies confirm some advantages of minimally invasive surgery, but for most types of laparoscopic and all types of thoracoscopic procedures, such data remain to be established. This article also focuses on reports on complications and disadvantages which are relevant for final conclusions and recommendations. The ethical implications of the application of new techniques in children are also discussed. On the basis of evidence based data and ethical principles, minimally invasive techniques may be appropriately used in the future.


Identification of alcoholism in young adults by blood chemistries.
A stepwise linear discriminant analysis was conducted between young adult alcoholics in an alcoholism treatment center and non-alcoholic college students. Analysis of 31 commonly ordered clinical laboratory tests yielded three significant variables (urea nitrogen, potassium and MCV) which correctly classify 89% of alcoholics and 92% of non-alcoholics.


The effects of beta1-adrenergic blockade on cardiovascular oxygen flow in normoxic and hypoxic humans at exercise.
At exercise steady state, the lower the arterial oxygen saturation (SaO(2)), the lower the O(2) return (QvO(2)). A linear relationship between these variables was demonstrated. Our conjecture is that this relationship describes a condition of predominant sympathetic activation, from which it is hypothesized that selective beta1-adrenergic blockade (BB) would reduce O(2) delivery (QaO(2)) and QvO(2). To test this hypothesis, we studied the effects of BB on QaO(2) and QvO(2) in exercising humans in normoxia and hypoxia. O(2) consumption VO(2), cardiac output Q, CO(2) rebreathing), heart rate, SaO(2) and haemoglobin concentration were measured on six subjects (age 25.5 +/- 2.4 years, mass 78.1 +/- 9.0 kg) in normoxia and hypoxia (inspired O(2) fraction of 0.11) at rest and steady-state exercises of 50, 100, and 150 W without (C) and with BB with metoprolol. Arterial O(2) concentration (CaO(2)), QaO(2) and QvO(2) were then computed. Heart rate, higher in hypoxia than in normoxia, decreased with BB. At each VO(2), Q was higher in hypoxia than in normoxia. With BB, it decreased during intense exercise in normoxia, at rest, and during light exercise in hypoxia. SaO(2) and CaO(2) were unaffected by BB. The QaO(2) changes under BB were parallel to those in Q.QvO(2) was unaffected by exercise in normoxia. In hypoxia the slope of the relationship between QaO(2) and VO(2) was lower than 1, indicating a reduction of QvO(2) with increasing workload. QvO(2) was a linear function of SaO(2) both in C and in BB. The line for BB was flatter than and below that for C. The resting QvO(2) in normoxia, lower than the corresponding exercise values, lied on the BB line. These results agree with the tested hypothesis. The two observed relationships between QvO(2) and SaO(2) apply to conditions of predominant sympathetic or vagal activation, respectively. Moving from one line to the other implies resetting of the cardiovascular regulation.


Identifying carbohydrate-active enzymes of Cutaneotrichosporon oleaginosus using systems biology.
The oleaginous yeast Cutaneotrichosporon oleaginosus represents one of the most promising microbial platforms for resource-efficient and scalable lipid production, with the capacity to accept a wide range of carbohydrates encapsulated in complex biomass waste or lignocellulosic hydrolysates. Currently, data related to molecular aspects of the metabolic utilisation of oligomeric carbohydrates are sparse. In addition, comprehensive proteomic information for C. oleaginosus focusing on carbohydrate metabolism is not available. In this study, we conducted a systematic analysis of carbohydrate intake and utilisation by C. oleaginosus and investigated the influence of different di- and trisaccharide as carbon sources. Changes in the cellular growth and morphology could be observed, depending on the selected carbon source. The greatest changes in morphology were observed in media containing trehalose. A comprehensive proteomic analysis of secreted, cell wall-associated, and cytoplasmatic proteins was performed, which highlighted differences in the composition and quantity of secreted proteins, when grown on different disaccharides. Based on the proteomic data, we performed a relative quantitative analysis of the identified proteins (using glucose as the reference carbon source) and observed carbohydrate-specific protein distributions. When using cellobiose or lactose as the carbon source, we detected three- and five-fold higher diversity in terms of the respective hydrolases released. Furthermore, the analysis of the secreted enzymes enabled identification of the motif with the consensus sequence LALL[LA]L[LA][LA]AAAAAAA as a potential signal peptide. Relative quantification of spectral intensities from crude proteomic datasets enabled the identification of new enzymes and provided new insights into protein secretion, as well as the molecular mechanisms of carbo-hydrolases involved in the cleavage of the selected carbon oligomers. These insights can help unlock new substrate sources for C. oleaginosus, such as low-cost by-products containing difficult to utilize carbohydrates. In addition, information regarding the carbo-hydrolytic potential of C. oleaginosus facilitates a more precise engineering approach when using targeted genetic approaches. This information could be used to find new and more cost-effective carbon sources for microbial lipid production by the oleaginous yeast C. oleaginosus.


Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis.
Hypoxia can induce cell injury in cardiomyocytes and further lead to cardiovascular diseases. Genistein (Gen), the predominant isoflavone found in soy products, has shown protective effects on cardiovascular system. The aim of the present study was to investigate the cardioprotective effect of Gen against chemical hypoxia-induced injury. Cobalt chloride (CoCl2) was administrated to trigger chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was detected by using MTT assay. The expression level of hypoxia-related proteins (hypoxia-inducible factor [HIF]-1α and Notch-1) and apoptosis-related proteins (B cell lymphoma [Bcl]-2, Bax, and caspase-3) were evaluated by Western blot analysis. In response to hypoxia, cell viability was reduced dramatically, whereas the expression of HIF-1α was upregulated. Hypoxia also induced cardiomyocytes apoptosis by reducing the ratio of Bcl-2/Bax and increasing expression of caspase-3. Interestingly, Gen attenuated CoCl2-induced cell death and suppressed HIF-1α expression, as well as upregulated the expression of Notch-1. Furthermore, Gen could antagonize CoCl2-induced apoptosis through upregulating Bcl-2/Bax ratio and inhibiting caspase-3 expression. Gen prevents chemical hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, exerting protective effects on H9c2 cardiomyocytes.


Magnetic resonance imaging appearance of primary squamous cell carcinoma of the breast.
Primary squamous cell carcinoma is a rare form of carcinoma of the breast. This article reports on two such lesions with their appearance in magnetic resonance imaging and reviews the scant English literature of the past 10 years. Most of these tumors are circumscribed and have areas of necrosis. The prognosis in patients with this disease is the same as that of adenocarcinoma of the same size and stage.


Lifelong learning: ocular dominance plasticity in mouse visual cortex.
Ocular dominance plasticity has long served as a successful model for examining how cortical circuits are shaped by experience. In this paradigm, altered retinal activity caused by unilateral eye-lid closure leads to dramatic shifts in the binocular response properties of neurons in the visual cortex. Much of the recent progress in identifying the cellular and molecular mechanisms underlying ocular dominance plasticity has been achieved by using the mouse as a model system. In this species, monocular deprivation initiated in adulthood also causes robust ocular dominance shifts. Research on ocular dominance plasticity in the mouse is starting to provide insight into which factors mediate and influence cortical plasticity in juvenile and adult animals.


To be or Not to be ridded?--That is the question addressed by the associative antigen recognition model.
The reasons that germline-encoded recognitive sites cannot sort the immune system's large and random somatically generated repertoire into anti-Not-to-be-ridded ('self ') and anti-To-be-ridded ('nonself ') specificities are analysed. The immune system cannot use 'nonself '-markers of To-be-ridded antigens ('Danger', toll receptors, pathogenicity, localization, etc.) to sort the repertoire; it may, however, use them to determine the magnitude and class of the effector response.


IConMHC: a deep learning convolutional neural network model to predict peptide and MHC-I binding affinity.
Tumor-specific neoantigens are mutated self-peptides presented by tumor cell major histocompatibility complex (MHC) molecules and are necessary to elicit host's anti-cancer cytotoxic T cell responses. It could be specifically recognized by neoantigen-specific T cell receptors (TCRs). However, current wet-lab assays for identifying peptide MHC binding are too expensive and time-consuming to meet the clinical needs. In this study, we developed an in silico method with a deep convolutional neural network (CNN) model, iConMHC, to predict peptide MHC binding affinity. Unlike other in silico methods that only learn from properties of amino acid in neoantigen peptides alone and/or MHCs alone, iConMHC learns from physical and chemical interaction properties between pairwise amino acids from the two molecules. These properties, such as contact potentials and distances in folded proteins, directly affect neoantigen-MHC binding affinity. In addition, IConMHC is a pan-allele model that is capable of making predictions for all the MHC alleles. Even for those rare MHC alleles without training data, iConMHC can make predictions with reasonable accuracy. We benchmarked iConMHC with other commonly used MHC-I binding predictors and found our model performs better than most of the pan-allele models.


Evaluating primary and booster vaccination prioritization strategies for COVID-19 by age and high-contact employment status using data from contact surveys.
The debate around vaccine prioritization for COVID-19 has revolved around balancing the benefits from: (1) the direct protection conferred by the vaccine amongst those at highest risk of severe disease outcomes, and (2) the indirect protection through vaccinating those that are at highest risk of being infected and of transmitting the virus. While adults aged 65+ are at highest risk for severe disease and death from COVID-19, essential service and other in-person workers with greater rates of contact may be at higher risk of acquiring and transmitting SARS-CoV-2. Unfortunately, there have been relatively little data available to understand heterogeneity in contact rates and risk across these demographic groups. Here, we retrospectively analyze and evaluate vaccination prioritization strategies by age and worker status. We use a mathematical model of SARS-CoV-2 transmission and uniquely detailed contact data collected as part of the Berkeley Interpersonal Contact Survey to evaluate five vaccination prioritization strategies: (1) prioritizing only adults over age 65, (2) prioritizing only high-contact workers, (3) splitting prioritization between adults 65+ and high-contact workers, (4) tiered prioritization of adults over age 65 followed by high-contact workers, and (5) tiered prioritization of high-contact workers followed by adults 65+. We find that for the primary two-dose vaccination schedule, assuming 70% uptake, a tiered roll-out that first prioritizes adults 65+ averts the most deaths (31% fewer deaths compared to a no-vaccination scenario) while a tiered roll-out that prioritizes high contact workers averts the most number of clinical infections (14% fewer clinical infections compared to a no-vaccination scenario). We also consider prioritization strategies for booster doses during a subsequent outbreak of a hypothetical new SARS-CoV-2 variant. We find that a tiered roll-out that prioritizes adults 65+ for booster doses consistently averts the most deaths, and it may also avert the most number of clinical cases depending on the epidemiology of the SARS-CoV-2 variant and the vaccine efficacy.


Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis.
The infiltration of monocytes-macrophages in the glomerulus is one of the hallmarks of glomerulonephritis and may play an important pathogenetic role. Monocyte chemoattractant protein-1 (MCP-1) and colony stimulating factor-1 (CSF-1) are monocyte-specific cytokines with chemoattractant and activating activities for monocytes. MCP-1 and CSF-1 can be generated by several cell types, including glomerular mesangial cells, and can be stimulated by cytokines and immune complexes. To study the expression of CSF-1 and MCP-1 in a model of proliferative glomerulonephritis we used Northern blot analysis and immuno-histochemistry. The glomerular lesion was induced in rats by the i.v. injection of a heterologous anti-thymocyte antiserum (ATS), directed against an antigen which is localized on glomerular mesangial cells. Northern blot analysis revealed comparable amounts of CSF-1 in glomeruli isolated from control untreated rats, and from rats after 30 minutes to three weeks of injection of ATS antibody. In control glomeruli no mRNA levels for MCP-1 were detectable, but increased markedly 30 minutes after the induction of the nephritis, were then reduced at 24 hours and increased again at 5 and 21 days after induction of the disease. The increase in mRNA levels for MCP-1 30 minutes or 24 hours after ATS injection was markedly attenuated if rats were complement depleted by cobra venom injection. These time points following antibody injection were associated with mesangial immune complex formation (30 min), mesangiolysis (24 hr) and proliferative glomerulonephritis (5 and 21 days). By immunohistology the presence of MCP-1 was demonstrated in glomeruli with a predominant mesangial distribution. The mesangial immunofluorescence for MCP-1 followed a pattern similar to that of the mRNA for MCP-1 after induction of the disease process, that is, it increased after 30 minutes, decreased after 24 hours and was increased again at three weeks. Within 30 minutes of the antibody injection an increased infiltration of monocytes-macrophages was observed in the glomeruli, which was maintained up to three weeks of induction of the glomerulonephritis. When the rats were decomplemented with cobra venom factor prior to the i.v. injection of ATS, the expression of MCP-1 in glomeruli remained low and the influx of monocytes/macrophages did not appear. We conclude that MCP-1 is increased early on in glomeruli of rats with immune-mediated mesangial proliferative glomerulonephritis. This increase is mediated by complement activation secondary to the in situ immune complex formation at the glomerular mesangium.(ABSTRACT TRUNCATED AT 400 WORDS)


The experience of hospitalized children regarding their interactions with nursing professionals.
The aim of this study is to describe the experience of children in their interactions with nursing professionals while in hospital. It is a qualitative study supported by the critical incident technique. Data was collected through participant observation and semi-structured interviews with thirty hospitalized children and teenagers between 8 and 14 years old. The results showed that children positively valued nursing care at the hospital and recognized that interactions with nursing staff included social and emotional factors. It is concluded that communication established with children plays a fundamental role to comprehend their experiences while in hospital. Therefore, nurses need to evaluate their strategies and relational skills used to interact with children at the hospital.


Philosophy of biology: outline of a transcendental project.
This paper analyses the actual meaning of a transcendental philosophy of biology, and does so by exploring and actualising the epistemological and metaphysical value of Kant's viewpoint on living systems. It finds inspiration in the Kantian idea of living systems intrinsically resisting objectification, but critically departs from Kant's philosophical solution in as far as it is based in a subjectivist dogmatism. It attempts to overcome this dogmatism, on the one hand by explicitly taking into account the conditions of possibility at the side of the subject, and on the other hand by embedding both the living and the knowing system into an ontology of complexly organized dynamical systems. This paper fits into the transcendental perspective in acknowledging the need to analyse the conditions of knowability, prior to the contents of what is known. But it also contributes to an expansion and an actualisation of the issue of transcendentality itself by considering the conditions of possibility at the side of the object as intrinsically linked to the conditions of possibility at the side of the subject.


Pulmonary hypertension in canine degenerative mitral valve disease.
Pulmonary hypertension secondary to degenerative mitral valve disease has been recognized clinically for many years in veterinary medicine, and clinical diagnosis of this syndrome in dogs has been enhanced greatly by widespread use of echocardiography and Doppler echocardiography. Medical therapy is now available to treat this clinical complication of mitral valve disease, making timely diagnosis even more important to patient longevity and quality of life.


Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.
Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation. Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Beck's Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed. Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus. Replication of the study with a larger sample size is required to increase the generalizability of these results. Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies.


Treatment of women with mild gestational diabetes mellitus decreases the risk of adverse perinatal outcomes.
Glycemic thresholds used to diagnose gestational diabetes mellitus (GDM) are a continued subject of debate. Lower glycemic thresholds identify women with milder GDM for whom treatment benefit is unclear. We compared adverse maternal and neonatal outcomes in treated and untreated women with mild hyperglycemia. We reviewed 11 553 patient charts from two tertiary care centers and included singleton pregnancies >32-week gestation. GDM was diagnosed using the one- or two-step 75 g oral glucose tolerance test (OGTT) depending on the center. All OGTT results were reviewed. Women with glycemic values falling between the thresholds of the two tests, referred to as intermediate hyperglycemic (IH), defined as FPG 5.1-5.2 mmol/L, 1 h PG 10.0-10.5 mmol/L, or 2 h PG 8.5-8.9 mmol/L at 75 g OGTT, were untreated at center A and treated at center B. There were 630 women with IH, 334 were untreated (center A) and 296 who were treated (center B). After adjusting for covariates, untreated IH women had significantly higher rates of gestational hypertension (aOR 6.02, P = 0.002), large for gestational age (LGA) (aOR 3.73, P < 0.001) and birthweights > 4000 g (aOR 3.35, P = 0.001). Our results indicate that treating 11 women with IH would prevent one LGA birth and treating 13 would prevent 1 birthweight > 4000 g. The diagnosis of GDM using the two-step OGTT fails to identify subgroups of women with mild hyperglycemia that would benefit from treatment to lower the risk for adverse maternal and neonatal outcomes. Treatment of women with mild hyperglycemia decreased the risk of LGA and birthweight >4000 g by 3-fold.


Nonhuman primate retroviruses from Cambodia: high simian foamy virus prevalence, identification of divergent STLV-1 strains and no evidence of SIV infection.
Nonhuman primates (NHPs) carry retroviruses such as simian immunodeficiency viruses (SIV), simian T-cell lymphotropic viruses (STLV) and simian foamy viruses (SFV). Here, we revisited NHPs from Cambodia to assess the prevalence and diversity of these retroviruses using updated viral detection tools. We screened blood from 118 NHPs consisting of six species (Macaca fascicularis (n=91), Macaca leonine (n=8), Presbytis cristata (n=3), Nycticebus coucang (n=1), Hylobates pileatus (n=14), and Pongo pygmaeus) (n=1) by using a Luminex-based multiplex serology assay that allows the detection of all known SIV/HIV and SFV lineages. We also used highly sensitive PCR assays to detect each simian retrovirus group. Positive PCR products were sequenced and phylogenetically analyzed to infer evolutionary histories. Fifty-three of 118 (44.9%) NHPs tested positive for SFV by serology and 8/52 (15.4%), all from M. fascicularis, were PCR-confirmed. The 8 novel SFV sequences formed a highly supported distinct lineage within a clade composed of other macaque SFV. We observed no serological or molecular evidence of SIV infection among the 118 NHP samples tested. Four of 118 (3.3%) NHPs were PCR-positive for STLV, including one M. fascicularis, one P. cristata, and two H. pileatus. Phylogenetic analyses revealed that the four novel STLV belonged to the PTLV-1 lineage, outside the African radiation of PTLV-1, like all Asian PTLV identified so far. Sequence analysis of the whole STLV-1 genome from a H. pileatus (C578_Hp) revealed a genetic structure characteristic of PTLV. Similarity analysis comparing the STLV-1 (C578_Hp) sequence with prototype PTLVs showed that C578_Hp is closer to PTLV-1s than to all other types across the entire genome. In conclusion, we showed a high frequency of SFV infection but found no evidence of SIV infection in NHPs from Cambodia. We identified for the first time STLV-1 in a P. cristata and in two H. pileatus.


On the evaluation of data from flow-dialysis experiments.
Flow dialysis can be used to measure (i) ligand binding to macromolecules and (ii) the size of transmembrane ion gradients. Generally an approximate method is used to calculate the binding or gradient parameters from the raw data. Here we present a simple but exact method and evaluate the errors that may arise when the approximate method is used to calculate the magnitude of ion gradients. In addition, equations are presented that allow for a correction for sampling from or additions to the upper compartment of a flow-dialysis vessel during the measurements. Setty and Hendler [(1982) J. Biochem. Biophys. Methods 7, 35-46] have reported artifacts in the measurement of ion-gradients caused by the addition of electron donors to the upper compartment of a flow-dialysis cell. Here we extend their observations and suggest additional methods to prevent such artifacts.


An Efficient Method for Computing Expected Value of Sample Information for Survival Data from an Ongoing Trial.
Decisions about new health technologies are increasingly being made while trials are still in an early stage, which may result in substantial uncertainty around key decision drivers such as estimates of life expectancy and time to disease progression. Additional data collection can reduce uncertainty, and its value can be quantified by computing the expected value of sample information (EVSI), which has typically been described in the context of designing a future trial. In this article, we develop new methods for computing the EVSI of extending an existing trial's follow-up, first for an assumed survival model and then extending to capture uncertainty about the true survival model. We developed a nested Markov Chain Monte Carlo procedure and a nonparametric regression-based method. We compared the methods by computing single-model and model-averaged EVSI for collecting additional follow-up data in 2 synthetic case studies. There was good agreement between the 2 methods. The regression-based method was fast and straightforward to implement, and scales easily to include any number of candidate survival models in the model uncertainty case. The nested Monte Carlo procedure, on the other hand, was extremely computationally demanding when we included model uncertainty. We present a straightforward regression-based method for computing the EVSI of extending an existing trial's follow-up, both where a single known survival model is assumed and where we are uncertain about the true survival model. EVSI for ongoing trials can help decision makers determine whether early patient access to a new technology can be justified on the basis of the current evidence or whether more mature evidence is needed. Decisions about new health technologies are increasingly being made while trials are still in an early stage, which may result in substantial uncertainty around key decision drivers such as estimates of life-expectancy and time to disease progression. Additional data collection can reduce uncertainty, and its value can be quantified by computing the expected value of sample information (EVSI), which has typically been described in the context of designing a future trial.In this article, we have developed new methods for computing the EVSI of extending a trial's follow-up, both where a single known survival model is assumed and where we are uncertain about the true survival model. We extend a previously described nonparametric regression-based method for computing EVSI, which we demonstrate in synthetic case studies is fast, straightforward to implement, and scales easily to include any number of candidate survival models in the EVSI calculations.The EVSI methods that we present in this article can quantify the need for collecting additional follow-up data before making an adoption decision given any decision-making context.


Anatomical study of the infra-montanal urethra in man.
Five samples infra-montanal prostatic urethra fixed in formalin and stored in liquid nitrogen at -30C were examined histologically. The results of this study demonstrated that muscle fibres of the striated sphincter extend as far as the level of the verumontanum. The proportion of rapid and slow striated fibres was identical. These striated fibres were mixed with smooth muscle fibres of the urethra. The density of innervation of this muscular tunic was found to increase closer to the striated sphincter; it is composed of equal numbers of adrenergic and cholinergic fibres.


Mechanism and stereochemistry of the germacradienol/germacrene D synthase of Streptomyces coelicolor A3(2).
Incubation of farnesyl diphosphate (1, FPP) with recombinant germacradienol synthase from Streptomyces coelicolor A3(2) gave, in addition to (4S,7R)-germacra-1(10)E,5E-diene-11-ol (2), 15% of (-)-germacrene D (5). Incubations of [1,1-2H2]FPP (1a), (1R)-[1-2H]FPP (1b), and (1S)-[1-2H]FPP (1c) with germacradienol/germacrene D synthase and analysis of the resulting samples of germacradienol (2) and germacrene D (5) by a combination of 1H, 2H, and 13C NMR and mass spectrometry established that it is H-1si of FPP that is lost in the formation of germacradienol (2) and that undergoes 1,3-hydride transfer in the formation of (-)-germacrene D (5). The proportion of the two products was also sensitive to isotopic labeling, with cyclization of (1S)-[1-2H]FPP (1c) giving an increased proportion (35%) of 5. These results could be explained by a mechanism involving partitioning of a common helminthogermacradienyl cation intermediate 7.


Heart rate variation during fetal behavioural states 1 and 2.
Fetal heart rate (FHR) variation was numerically assessed in relation to behavioural states in 34 normal near term fetuses, in order to study the normal ranges of FHR variation during state 1F and 2F and to determine possible factors influencing variation in these states. In all individuals 2-h recordings were made of fetal heart rate, and body and eye movements. FHR variation was quantified using the Sonicaid System 8000. During both 1F and 2F there was a large range in variation, with a wide overlap in variation between both states (mean 1-min range in pulse intervals 16-53 ms and 36-97 ms, respectively). In all fetuses variation was higher during 2F than during 1F. The large ranges in variation were mainly caused by differences in basal heart rate and the correlation coefficients between rate (beats/min) and variation were -0.68 and -0.49 for 1F and 2F, respectively. Other reasons for a relatively high FHR variation during 1F included 'pseudo' sinusoidal patterns related to fetal sucking or mouth movements and relatively flat periods sporadically interrupted by an acceleration. With the System 8000, periods of low and high variation are identified using fixed criteria. Because of the large overlap in variation between both states, these episodes poorly correlated with the underlying behavioural states. Objective identification of the heart rate patterns during states 1F and 2F requires incorporation of heart rate itself in the analysis. As yet, 'global' visual identification of heart rate patterns is superior to computer analysis in identifying the underlying fetal behavioural states.


Incorporation of the emotional indicators of the patient journey into healthcare organization management.
In recent years, attempts have been made to incorporate patients' experiences into healthcare processes, to complement clinical indicators, with what are known as patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). While the research into PROMs is more developed, the application of PREMs faces some difficulties. The incorporation of emotional indicators into assessments of the experience is an area that remains to be explored. This study proposes a new technique to analyse the emotions experienced by patients during the care process, examines how these emotions influence their satisfaction and propose that if healthcare services focus more on patients' emotions, they can improve the effectiveness of the sector. The first, qualitative stage, gathered data from patients to design a patient journey (PJ). The PJ was then reproduced as a video. In a subsequent, quantitative stage, the video was shown to experimental participants, and their emotions were measured through facial expression analysis and a questionnaire. A new technique to gather emotional data showed that the emotions patients experience do not affect their satisfaction with their clinical care or the physical aspects of the process. However, their emotions did affect their satisfaction with people and organizations. The importance of the emotional component of patients' experiences was underlined. Therefore, healthcare organizations should take account of this dimension, as well as the cognitive, to increase patient satisfaction and improve their care processes. Understanding the impact of the emotions identified at the subconscious level can help improve the patient experience. A new methodology was applied that may help health professionals to collect emotional data about patients' experiences and to develop PREMs. Patients were involved in all stages of this research. In the exploratory phase, some helped define the touchpoints of the PJ. The data from the subsequent experimental phase were collected from another group, and the emotions they experienced were identified through the analysis of their facial expressions. Based on the results of this study, a working group including patients has been established to work on improvements in the PJ.


Hydromyelia associated with arrested hydrocephalus.
A 16-year-old male with a 9-year history of spontaneously arrested hydrocephalus was noted to have hydrosyringomyelia and increased intracranial pressure shortly after sustaining minor head trauma. His symptoms resolved completely following ventriculoperitoneal shunt replacement. Hydrosyringomyelia may occur in the setting of long-standing, apparently arrested hydrocephalus.


Surgical management on a rare type of vertical liner fracture of tibia: A case report study.
The vertical liner fracture of the tibia is an infrequent and intricate injury that presents considerable difficulties in terms of its diagnosis, treatment, and long-term consequences. This particular fracture pattern is distinguished by a vertical line of fracture along the length of the tibial shaft, spanning from the proximal to the distal end. The 31-year-old female patient, who had no prior medical conditions, presented to the emergency department with complaints of intense pain and impaired ambulation in her right lower limb. She reported an accidental fall while descending a staircase, resulting in substantial impact and pressure on her right leg. While fractures of the tibia are frequently encountered, there exist exceptional instances of vertical liner fractures within this category. A vertical long liner fracture of the tibia denotes a distinct fracture type in the elongated bone of the lower limb, characterized by a vertical fracture line that extends along the length of the bone. Vertical liner fractures of the tibia, although rare, are distinct from more common tibial fracture patterns. Accurate diagnosis and thorough evaluation using various imaging methods are crucial for assessing the extent of the fracture and any associated injuries.


Social stress and suicide: replicating an Asian study with American data.
A study purporting to show an association between social stress and attempted suicide in Hong Kong utilized an incorrect regression specification. The study was replicated with American time-series data and, using the correct specification, social stress was positively associated with suicide rates.


Boosting the electrochemical performance of Li-rich Mn-based cathode materials via oxygen vacancy and spinel phase integration.
Li-rich Mn-based oxide cathodes (LMOs) are regarded as one of the most prospective high energy density cathodes due to the reversible anion redox reaction, which gives them a very high capacity. However, LMOs materials usually have problems like low initial coulombic efficiency (ICE) and poor cycling performance during cycling, which are associated with irreversible surface O2 release and unfavourable electrode/electrolyte interface side reactions. Herein, an innovative and scalable NH4Cl-assisted gas-solid interfacial reaction treatment technique is employed to construct oxygen vacancies and spinel/layered heterostructures simultaneously on the surface of LMOs. The synergistic effect of the oxygen vacancy and the surface spinel phase can not only effectively enhance the redox properties of the oxygen anion and inhibit irreversible oxygen release, but also effectively mitigate the side reactions at the electrode/electrolyte interface, inhibit the formation of CEI films and stabilize the layered structure. The electrochemical performance of the treated NC-10 sample improved significantly, showing an increase in ICE from 77.4 % to 94.3 % and excellent rate capability and cycling stability, with a capacity retention of 77.9 % after 400 cycles at 1 C. This oxygen vacancy and spinel phase integration strategy offers an exciting prospect and avenue for improving the integrated electrochemical performance of LMOs.


Paterson-Brown Kelly Syndrome (also commonly known as Plummer-Vinson Syndrome).
The dysphagia in this condition is usually associated with iron deficiency anemia and esophageal webs. Iron supplementation and regular surveillance are required for monitoring of malignant transformation into esophageal squamous cell carcinoma.


Peroxidase-like activity of Fe-N-C single-atom nanozyme based colorimetric detection of galactose.
Single atom nanozymes are the artificial enzymes with enzyme-like activity, which have attracted a great deal attention in recent years due to their unique merits such as remarkable stability, excellent atom utilization and low cost. Herein, a convenient and sensitive colorimetric strategy was developed for the sensing of galactose based on Fe-N-C single-atom nanozyme (Fe-SAzyme). The Fe-SAzyme was prepared through "isolation-pyrolysis" method that exhibited intrinsic peroxidase mimicking activity, which can quickly catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue-colored oxTMB in the presence of hydrogen peroxide (H2O2). Galactose can be oxidized by galactose oxidase (Gal Ox) to generate H2O2, and Fe-SAzyme can be utilized for quantitative colorimetric detection of galactose. A good linearity between absorbance and the galactose concentration in the range of 50-500 μM was obtained with a detection limit of (LOD) 10 μM. The Fe-SAzyme based colorimetric strategy offered a rapid, convenient and economic way for galactose quantification detection, which could be used as an alternative method for galactosemia diagnosis.