Improved patient-reported outcomes after open preperitoneal inguinal hernia repair compared to anterior Lichtenstein repair: 10-year ACHQC analysis.
The Lichtenstein repair has been synonymous with "open" inguinal hernia repair (IHR) for 40 years. However, international guidelines have suggested that posterior mesh placement results in advantageous biomechanics and reduced risk of nerve-related chronic pain. Additionally, the use of local anesthetics has been shown to reduce postoperative pain and complication risks. An open transrectus preperitoneal/open preperitoneal (TREPP/OPP) repair combines posterior mesh placement with the use of local anesthetic and as such could be the ideal repair for primary inguinal hernia. Using the Abdominal Core Health Quality Collaborative (ACHQC) registry, we compared open anterior mesh with open posterior mesh repairs. We performed a propensity score matched analysis of patients undergoing open IHR between 2012 and 2022 in the ACHQC. After 1:1 optimal matching, both the TREPP/OPP and Lichtenstein cohorts were balanced with 451 participants in each group. Outcomes included patient-reported quality of life (QoL), hernia recurrence, and postoperative opioid use. Improvement was seen after TREPP/OPP in EuraHS QoL score at 30 days (OR 0.558 [0.408, 0.761]; p = 0.001), and the difference persisted at 1 year (OR 0.588 [0.346, 0.994]; p = 0.047). Patient-reported opioid use at 30-day follow-up was significantly lower in the TREPP/OPP cohort (OR 0.31 [0.20, 0.48]; p < 0.001). 30-day frequency of surgical-site occurrences was significantly higher in the Lichtenstein repair cohort (OR 0.22 [0.06-0.61]; p = 0.007). There were no statistically significant differences in hernia recurrence risk at 1 year, or rates of postoperative bleeding, peripheral nerve injury, DVTs, or UTIs. Our analysis demonstrates a benefit of posterior mesh placement (TREPP/OPP) over anterior mesh placement (Lichtenstein) in open inguinal hernia repair in patient-reported QoL and reduced opioid use.


Hevein, a lectin-like protein from Hevea brasiliensis (rubber tree) is involved in the coagulation of latex.
Hevein, a lectin-like protein is the major protein of vacuolar structures called lutoids in the latex of rubber trees. We have shown both by in planta and ex planta studies that hevein is involved in the coagulation of latex by bringing together rubber particles. This polyvalent bridging between hevein and rubber particles is mediated by N-acetyl-D-glucosamine and involves a receptor glycoprotein of 22 kDa, which is localized on the surface of the rubber particles. The proposed role of hevein helps us to understand the mechanism of coagulation of latex and assigns a physiological intracellular function to one of the smallest lectins.


Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresis.
The renin-angiotensin-aldosterone system is activated by diuretics and involved in the diuretic resistance of cirrhotic patients with ascites and oedema. In previous studies relatively high doses of captopril (25-400 mg daily) were unsuccessful in promoting diuresis and natriuresis in these patients. We analyzed the efficacy of a low dose of captopril in eight patients with massive ascites resistant to therapy of salt/fluid restriction and increasing doses of spironolactone and furosemide. Mean duration of diuretic use was 73 days (range 7-240 days). After at least 3 days of observation on 80 mg furosemide and 100 mg spironolactone only, captopril was added. Four out of eight patients responded with an increase in natriuresis and diuresis; daily dose of captopril was 20.6 mg in responders and 26.5 mg in non-responders. After the addition of captopril the mean weight change was -7.5 kg in responders and +0.25 kg in non-responders. Mean urinary sodium output in responders increased from 72.8 (S.D. = 35.2) to 128.5 (63.5) mmol within 10 days. Increased diuresis in responders made diuretic reduction necessary: mean furosemide from 80 to 53.3 mg, and mean spironolactone from 100 to 68.1 mg. Creatinine clearances remained stable. High levels of plasma renin activity, plasma aldosterone and angiotensin-II were found in all patients. Non-responders showed more severe hyponatremia and higher vasopressin levels. Natriuretic atrial factor (NAF) was in the upper-normal range or slightly elevated in both groups. In non-responders we noticed low levels of cGMP in 24-h urine, compared with responders.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of T lymphocyte activation by estramustine: dose-dependent interference with IL-2 production and later proliferation events.
Estramustine, a nitrogen mustard derivative of estradiol-17 beta widely used for treatment of prostatic cancer, was found to inhibit the proliferative response of mouse lymphocytes to T (concanavalin A) and B (lipopolysaccharide) cell mitogens in vitro. Concanavalin A-induced lymphoproliferation was considerably more sensitive to the antiproliferative effect of estramustine than lipopolysaccharide-stimulated proliferation. The concentration of estramustine selectively inhibiting T lymphocyte proliferation was only active when present during the first 24 h of culture and could be overcome by exogenously added interleukin 2. Estramustine was shown to directly inhibit the production of interleukin 2 in concanavalin A-stimulated lymphocyte cultures without affecting the expression of interleukin 2 receptors. Thus the preferential inhibitory effect of estramustine on mitogen-induced T lymphocyte activation is apparently mediated by interference with the production or release of interleukin 2.


[The role of matrix vesicles during development of the mineralizing tissues of tooth germ and craniofacial bone].
To evaluate the role of matrix vesicles (MVs) during the development of mineralizing tissues. The ultrastructure of MVs of tooth germ, calvarial bone and mandibular bone were observed by transmission electron microscopy in fetal Wistar rat. (1) The MVs were formed by osteoblast of the secret type, dentinoblast and process; (2) There was a mature process of the MVs in the extracellular matrix. The appearance of the hydroxyapatite (HAP) was a major mature feature; (3) HAP formed initially in the MVs entered into collage matrix and eventually mineralized; (4) The shifting sign of HAP from MVs to the surface of collage fibril was observed. The MVs played an important role in the biomineralization, but the special arrange pattern of mature collage fiber provided a suitable environment and a model to the growth of HAP for further mineralization.


Conjunction of standing wave and resonance in asymmetric nanowires: a mechanism for thermal rectification and remote energy accumulation.
As an important way to control and manage heat transport, thermal rectification has become an elementary issue in the field of phononics and plays a key role in the designing of thermal devices. Here we investigate systematically the standing wave and the accompanying resonance process in asymmetric nanowires to understand the standing wave itself and its great effect on thermal rectification. Results show that the standing wave is sensitive to both the structural and thermal properties of the material, and its great effect on enhancing the thermal rectification is realized not only by the energy-localization nature of the standing wave, but also by the resonance-caused large amplitude and high energy of the standing wave.


Toxicodynamic analysis of inflammatory reactions by an angiotensin converting enzyme inhibitor (lisinopril) in guinea-pig skin.
There have been reports of rash and angioedema in the treatment of hypertension with angiotensin converting enzyme (ACE) inhibitors. To evaluate the inflammatory reaction, we continuously infused lisinopril for three days into the peritoneal cavity of ovalbumin-sensitized guinea-pigs and tested intradermal inflammation with ovalbumin. Inflammatory responses were measured in two perpendicular directions serially, and the areas of rash were used as an index of inflammatory reaction induced by lisinopril. Inflammatory responses were dose-dependently enhanced by treatment with lisinopril. Plasma concentration of lisinopril required to produce 50% of the maximum potentiation of the inflammatory reaction in guinea-pig skin was 40 times plasma unbound concentration after the clinical treatment of lisinopril in patients.


Implicit and Explicit Stigma of Chronotype in Emerging Adults.
Individuals with poor sleep (e.g., insomnia) and mental health (e.g., depression) experience negative stigma but no studies have examined the relationship between stigma and evening chronotype. The present mixed methods study aimed to assess and describe explicit and implicit attitudes about evening and morning chronotypes in a sample of emerging adults. 49 undergraduates (Mage = 19.9 [SD = 1.5], 83.7% female). Participants completed self-reports of demographics and chronotype. Attitudes about "night owls" and "early birds" were measured with self-report questionnaires (explicit attitudes) and an Implicit Association Task (implicit attitudes). Participants described associations with evening and morning chronotypes in free-text responses, which were qualitatively coded. We found evidence of implicit bias against night owls and for early birds. The positive mean implicit d score was 0.57 (SD = 0.47), indicating a moderate implicit bias for pairing "bad" with "night owl" and "good" with "early bird." No baseline characteristics, including chronotype, were significantly associated with implicit bias. Analyses of explicit bias revealed participants perceived night owls as significantly more lazy, unhealthy, undisciplined, immature, creative, and young. Analysis of free-text responses provided further evidence of these associations. Consistent with hypothesis, undergraduates demonstrated predominantly negative implicit and explicit stigma toward evening chronotypes compared to morning types. As stigma can lead to adverse consequences, future studies should assess the impact of negative societal and self-stigma on evening types. Consideration of societal stigma within clinical intervention contexts could have the potential to reduce shame or other emotions that interfere with sleep.


Development of a clinical risk score system for peritoneal dialysis-associated peritonitis treatment failure.
This study aimed to construct a clinical risk score system for peritoneal dialysis-associated peritonitis (PDAP) treatment failure to provide a theoretical basis for clinical workers. A total of 161 PDAP individuals admitted to our hospital were included, among whom 70 cases were in the treatment-improved group and 87 cases were in the treatment failure group. We compared the general condition, clinical manifestations, and laboratory examination indicators of the two groups of individuals, used multivariate logistic regression analysis to identify the factors influencing PDAP treatment failure, and developed a clinical risk score system. The diagnostic performance of the risk score system was evaluated utilizing the receiver operating characteristic (ROC) curve. Significant differences (P < 0.05) were observed between the two groups in terms of contamination, peritoneal fluid culture results, blood urea nitrogen (BUN) level, C-reactive protein (CRP) level, B-type natriuretic peptide (BNP) level, average residual urine (RU) volume, and urea clearance rate (UCR). Multivariate logistic regression analysis showed that BUN level, CRP level, BNP level, average RU volume, and UCR were independent risk factors affecting PDAP patient treatment outcomes (P < 0.05). The ROC curve analysis of the risk score system for predicting treatment failure in PDAP individuals showed an area under the curve of 0.895 [95% confidence interval (0.847-0.943)]. The optimal cut-off point was 2.5 points, with corresponding sensitivity and specificity of 88.5% and 74.3%, separately. BUN level, CRP level, BNP level, average RU volume, and UCR are independent risk factors for PDAP treatment failure. The clinical risk score system based on these five independent risk factors can accurately predict the risk of treatment failure in PDAP individuals.


Awake craniotomy in a super obese patient using high flow nasal cannula oxygen therapy (HFNC).
Super obesity with a body mass index (BMI) >50 kg/m2 presents a challenge for the neuroanesthesiologist during awake craniotomy procedures and poses increased perioperative risk of complications, even vis-à-vis morbid obesity. This article presents a super obese patient (BMI 57 kg/m2) with drug-refractory epilepsy and obstructive sleep apnea who underwent left anterior temporal lobectomy through awake craniotomy to preserve language and memory, using warmed humidified high flow nasal cannula (HFNC) oxygen therapy. Awake craniotomy was facilitated by the use of HFNC, which proved essential to prevent airway collapse by creating continuous positive airway pressure through high flow and facilitated intraoperative neurologic language and memory testing while maintaining adequate oxygenation.


Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder.
The basis for carbamazepine's efficacy in treating bipolar disorder is not agreed on. One hypothesis is that, similar to lithium and valproate (antibipolar drugs), carbamazepine might selectively decrease the kinetics of arachidonic acid (AA) in brain phospholipids. To assess whether it targets brain AA kinetics, we administered carbamazepine (25 mg/kg/day, IP) to rats for 30 days and then determined its effect compared with that of vehicle on incorporation and turnover rates of AA and docosahexaenoic acid (DHA) in brain phospholipids. In unanesthetized rats that had received carbamazepine or vehicle, [1-14C]AA or [1-14C]DHA was infused intravenously, and arterial blood plasma was sampled until the animal was killed at 5 min and its brain, after being microwaved, was used for acyl-coenzyme A (acyl-CoA) and phospholipid fatty acid analysis. Chronic carbamazepine, compared with vehicle, decreased the rate of incorporation of AA-CoA (27%-29%) and turnover of AA (25%-27%) but not of DHA-CoA or DHA in brain phospholipids. The results, which are comparable to published findings after chronic administration of lithium and valproic acid to rats, support the hypothesis that drugs effective against mania in bipolar disorder act by selectively downregulating the incorporation rate of AA-CoA and turnover of AA in brain phospholipids.


Perinatal exposure to benzyl butyl phthalate induces alterations in neuronal development/maturation protein expression, estrogen responses, and fear conditioning in rodents.
Phthalate exposure has recently been associated with behavioral actions that are linked to its endocrine-disrupting properties. The purpose of this study was to investigate the molecular, anatomical, and behavioral effects of indirect perinatal benzyl butyl phthalate (BBP) exposure in offspring of BBP-treated pregnant dams. In two separate experiments, we administered BBP (10.0 μg/ml) on food pellets to pregnant dams and examined the offspring. The first experiment revealed reproductive anatomical abnormalities linked to BBP's endocrine-disrupting properties, whereas histological analysis revealed preserved hippocampal neuronal migration. The second experiment demonstrated learning and memory impairments accompanied by molecular abnormalities in multiple brain regions. Offspring from BBP-treated dams had altered levels of several proteins important for neuronal circuitry formation, tissue development, and maturation. We suggest that BBP administration disrupts normal learning and that these effects could be related to alterations in brain development and result in a phenotype similar to that observed in neurodevelopmental disorders.


Innovative radiotherapy of sarcoma: Proton beam radiation.
This review on proton beam radiotherapy (PBT) focusses on an historical overview, cost-effectiveness, techniques, acute and late toxicities and clinical results of PBT for sarcoma patients. PBT has gained its place among the armamentarium of modern radiotherapy techniques. For selected patients, it can be cost-effective.


The spatial distribution of fungi on decomposing alder leaves in a freshwater stream.
Transects were cut from alder leaves incubated in a freshwater stream and plated as quadrats so that fungal isolates could be mapped by reconstruction of each transect. Initially there was fewer than one aquatic hyphomycete colonist per quadrat, but the mode increased to 6-7 then progressively decreased to <1. Numbers of species of aquatic hyphomycetes per quadrat rose and fell similarly with a maximum mode of 3-4, as did species per transect with a maximum of 11 and a diversity of 16, comprising 6 'dominant' species and about 10 'occasional' species. The latter showed no pattern of appearance but the dominant group was established early and persisted in a dynamic equilibrium. Aquatic hyphomycetes were initially randomly distributed but developed progressively into clumped consortia which persisted after peak colonization, declining as leaf degradation became total. Colonies of the most persistent aquatic hyphomycete species were initially discrete,developing into a complex network of overlapping colonies and species, no two of which showed positive association. These complexes broke down to large colonies of a few species and finally to 1-2 small colonies. The pattern of isolates of the 18 genera of other fungi was the reverse of that for aquatic hyphomycetes. Only Cladosporium, Epicoccum and Fusarium were important colonizers. The first two appear to be inhibited by aquatic hyphomycetes, but were found to degrade substrates representative of cell-wall polymers vigorously whereas aquatic hyphomycetes showed varied degradative ability. Leaf transects were examined by S.E.M. and epifluorescent microscopy so that hyphal colonization could be followed at progressive stages of leaf degradation. Bacteria on transects were patchily distributed, the temporal pattern indicating inhibition by aquatic hyphomycetes and colonization of senescent hyphae.


Integrative multilevel exploration of the mechanism by which Er-Zhi-Wan alleviates the Parkinson's disease (PD)-like phenotype in the MPTP-induced PD mouse model.
The neuroprotective effects of Er-Zhi-Wan (EZW), a well-known traditional Chinese formulation, in MPTP-induced Parkinson's disease (PD) models are poorly understood and require evaluation. A model of PD induced by MPTP was used to evaluate the neuroprotective effects of EZW in mice. The underlying pharmacological mechanisms of EZW for the prevention and treatment of PD were then explored using a combination of multilevel databases, network pharmacology, biological experiments, and LCMS/MS. In vivo data showed that pretreatment with EZW can be neuroprotective against MPTP-induced motor dysfunction and can effectively rescue dopaminergic neurons from MPTP-induced degeneration in mice. Furthermore, data from combined multilevel databases and network pharmacology analysis strategies suggested that the neuroprotective activity of EZW in the treatment of PD is mediated by a complicated multicomponent, multitarget network. Genes such as Grm2, Grm5, Drd2, and Grik2 were identified as important therapeutic targets. Subsequent experimental validation showed that EZW can broadly regulate the mRNA levels of these receptor genes as well as BDNF, and consequently increase the phosphorylation levels of CREB to stimulate CREB signaling. These targets and signaling systems may be responsible for the reversal of neuronal death by EZW after MPTP exposure. The LC-MS/MS results also identified a wide range of chemical components of EZW, including at least 53 precise compounds, further demonstrating the complexity of the network in which EZW exerts its neuroprotective activity. Our work provides evidence for the mechanism of EZW in MPTP-PD models and supports the neuroprotective function of EZW in neurodegenerative diseases.


Optimal application of high-frequency ventilation in infants: a theoretical study.
A recent multicenter study of preterm infants concluded that high-frequency ventilation (HFV) applied at 15 Hz, in comparison with conventional mechanical ventilation (CMV), did not lead to reduced incidence of barotrauma, contrary to previous expectations. The primary goal of the present theoretical study was to determine whether computed estimates of lung pressures during HFV and CMV are consistent with these findings. An existing theoretical model of lung mechanics and gas transport in HFV was modified for applicability to neonates. New features, such as expiratory flow limitation and pulmonary air leak, were also incorporated. Simulations with the model were conducted assuming combinations of frequency and tidal volume that maintained a constant level of eucapnia. We found that peak alveolar pressures and the magnitude of alveolar pressure swings resulting from HFV at 15 Hz were in general comparable to those produced by CMV in healthy neonates and infants with bronchopulmonary dysplasia; peak alveolar pressures in the latter group tended to be higher with HFV than in CMV. Application of HFV at 15 Hz was even less advantageous than CMV when pulmonary air leak was also present in the infants with bronchopulmonary dysplasia. However, the model predicted the existence of an optimal range of frequencies between 2 and 4 Hz in which alveolar pressure swings and peak alveolar pressures could be minimized, and in some cases, reduced below the levels produced by CMV.


Ventricular remodeling in Loeffler endocarditis: implications for therapeutic decision making.
Little is known about the morphological and functional evolution of ventricular abnormalities in Loeffler endocarditis. We describe 5 patients, including 3 with long-term echocardiographic follow-up, in whom apical obliteration due to fibro-thrombotic thickening of the endocardium showed favorable patterns of evolution. In one patient there was almost complete resolution of the obliterative process with consequently increased effective ventricular volume. In two patients formation of a flow-passage in the fibrocalcific apical 'floor' between the main medioventricular cavity and the apical chamber, leading to a 'double-chambered' left ventricle was observed. Medical therapy and appropriate anticoagulation, can induce favorable long-term ventricular remodeling in Loeffler endocarditis.


Effects of sperm protamine on human cervical epithelial cells and BHK 21 cells in vitro.
The addition of protamine, of both human and animal origin, to cultures of epithelial and fibroblastic cells has demonstrated that this component of sperm proteins may be capable of bringing about neoplastic transformation in vitro.


Effective removal of polymer quaternary ammonium salt by biodegradation and a subsequent Fenton oxidation process.
In this paper, a process combining biodegradation and Fenton oxidation was proposed for the removal of polydiallyldimethylammonium chloride-acrylic-acrylamide-hydroxyethyl acrylate (PDM) in aqueous phase. Biodegradation of PDM was investigated in activated sludge systems, and the effects of the solution pH, mixed liquid suspended solids (MLSS), salinity, co-substrate, and initial substrate concentration, were studied. The biodegradation process was well-described with the Monod model and the values of the kinetics parameters vmax, ks were 0.05 h-1 and 333 mg/L. The optimal biodegradation conditions in the experimental range were determined to be: pH = 7.0, 0%-0.01% (w/v) NaCl, 4000 mg/L of MLSS, and 500 mg/L of glucose as co-substrate. FT-IR analysis indicated that PDM molecules biodegradation partly. The microbial community structures and dehydrogenase activity analysis revealed that PDM showed some toxicity to microorganisms in activated sludge. The effects of several parameters, including the pH and chemical doses, were investigated for removing PDM in Fenton oxidation process. The optimal Fenton oxidation process conditions in the experimental range were pH = 2.0, Fe2+ concentration of 40 mg/L, and H2O2 dosage of 23 mL/L. PDM was treated by biodegradation and subsequent Fenton oxidation under the optimal operating conditions. The removal efficiency was 44.5% after the biodegradation process and further increased to 85.5% after Fenton oxidation. The combined process was revealed to be a promising solution for achieving effective and economical removal of PDM.


The effect of varying head tilt on the perceived color from composite resin and porcelain restorations: Simulating the effect of altering torque.
This study aimed to assess the effect of changes in tooth torque on the perceived color of composite and porcelain restorations. A total of 30 patients with previous composite restorations and 30 patients with porcelain restorations on lateral and central incisors were selected. To simulate the effect of dental torque change, we asked the patients to tilt their heads upwards and downwards to represent buccal and palatal crown torque, respectively. Photographs were taken in 3 different positions (natural head position, 15° upward tilt, and 15° downward tilt). A laser alignment tool was used to help with head positioning. Color was measured on the 3 principal axes of the Commission Internationale de L'Eclairage, L∗, a∗, and b∗ color space using Photoshop software (Adobe, San Jose, Calif), and color differences were calculated. The midpoint of the clinical crown, both mesiodistally and incisogingival, was selected as the point of measurement. A general linear model was used to analyze the significance of changes in each value of different tooth torques. A t test was used to compare color changes of 2 different incisors (central and lateral) and overall color differences in the 2 types of restoration. Significant changes of the L∗ and a∗ values were found as a result of the change in head inclination, whereas b∗ values remained unchanged. It was found that buccal crown torque resulted in lighter and greener porcelain restorations. Composite restorations behaved similarly with the only difference being that the central incisors appeared bluer. Palatal crown torque resulted in a darker and redder porcelain restoration and a darker, redder, and yellower composite restoration. No significant differences were found between color changes in the central and lateral incisors. Furthermore, porcelain and composite restorations had similar color changes with alteration of head inclination. Orthodontic changes of tooth torque alter the color perceived from composite and porcelain restorations.


Living conditions of serious chronic respiratory insufficiency patients treated at home on oxygen therapy or assisted ventilation.
A study on the living conditions of patients on long-term oxygen therapy or assisted ventilation at home was conducted in France in January 1988. At that date, 13,500 patients had been handled by 30 regional associations. Twenty-four regional associations (80%) representing 11,079 patients (82%) participated in the study. A total of 8,091 questionnaires were processed, accounting for 73% of patients interviewed and 60% of the population under treatment.


Molecular characterization of a normal Hb A2 beta-thalassaemia determinant in a Sardinian family.
In this study we have carried out haplotype analysis at the beta-globin gene cluster and defined the beta-thalassaemia mutations in a large Sardinian family, ascertained through a proband with thalassaemia major, in which several members were carriers of a beta-thalassaemia allele characterized by microcytosis, hypochromia and normal Hb A2 levels (type 2 normal Hb A2 heterozygous beta-thalassemia). The proband was a compound heterozygote for the beta zero 39 and the beta + IVS-2, nt 745 mutations and all the beta-thalassaemia heterozygotes with normal Hb A2 showed the beta + IVS-2, nt 745 mutation, always associated with haplotype VII. Because of the consistent association of a specific beta-thalassaemia mutation and normal Hb A2 levels, we postulate that this beta-thalassaemia chromosome carries a delta gene (delta-thalassaemia) which is unable to increase the delta-globin output in response to beta-thalassaemia.


A new approach toward the stereoselective synthesis of novel benzo[b][1,5]oxazepines using MCM-41(H) zeolite.
Facile procedures have been developed for the stereoselective synthesis of novel benzo[b][1,5]oxazepines 4a-f by the condensation reaction between 2-amino phenol 2 and tert-butyl(4R)-2,2-dimethyl-4-(3-oxo-3-phenyl-1-propynyl)-1,3-oxazolane-3-carboxylate 3a-f with MCM-41(H) zeolite in acetonitrile.


The technique of transvaginal sonography with the use of a 6.5 MHz probe.
Ultrasonography has become an important tool in infertility and obstetric practice. Its use in gynecology, while effective, has been less. This article describes the use of a high-frequency 6.5 MHz probe specially designed for intravaginal use. The technique is presented, along with a description of its uses and findings by organ. Patient acceptance has been universal. Its high resolution makes this technique more useful in general gynecologic practice.


[Necrotizing enteritis in nursing piglets (Clostridium perfringens type C enterotoxemia) in industrialized swine breeding facilities].
Outbreaks of necrotising enteritis, caused by Clostridium perfringens, Type C, among piglets on five industrialised breeding units are reported in this paper. Original diagnosis was confirmed by clinical, pathologico-anatomic, histological, and bacteriological tests as well as by the detection of beta toxin from the intestinal matter of piglets after death. Cl. per fringens, Type C, was successfully isolated from 71.9 per cent of all animals that had died of necrotising enteritis. Three forms were differentiated by pathologico-anatomic findings: 1. haemorrhagic-necrotising enteritis with excessive bleeding of the intestinal wall and blood loss into the intestinal lumen; 2. necrotising enteritis with small scattered foci of bleeding; 3. necrotising enteritis without any bleeding. The first form usually developed concomitantly with peracute and acute disease in the first three days of age, whereas the third form was primarily recorded from piglets that had died, following subacute disease, between the fourth and ninth days after birth.


Influence of pH on the speciation of copper(II) in reactions with the green tea polyphenols, epigallocatechin gallate and gallic acid.
Changes in speciation of copper(II) in reactions with epigallocatechin gallate (EGCG) and gallic acid (GA) as a function of pH have been investigated by multifrequency (X- and S-band) EPR spectroscopy in the fluid and frozen states. The EPR spectra show the formation of three distinct mononuclear species with each of the polyphenols, and these are interpreted in terms of one mono- and two bis-complexes. However, di- or polymeric complexes dominate the Cu(II) speciation in the pH range 4-8, and it is only at alkaline pH values that these mononuclear complexes make appreciable contributions to the metal speciation. Each mononuclear complex displays linewidth anisotropy in fluid solution as a consequence of incomplete averaging of the spin Hamiltonian parameters through molecular motion. Rotational correlation times for the individual complexes have been estimated by analysing the lineshape anisotropy of the fluid solution spectra using parameters determined by simulation of the rigid limit spectra. These show that the molecular masses increase with increasing pH, indicating either coordination of increasing numbers of polyphenol molecules as ligands to the copper or the increasing involvement of polyphenol dimers as ligands in the copper coordination sphere.


The Left Outflow Tract in Fetal Cardiac Screening Examination: Introduction of Quality Criteria Is Not Always Associated With an Improvement of Practice When Supervised by Humans.
Since 2016, the French CNEOF included the left ventricular outflow tract (LVOT) in the second and third trimester of pregnancy in addition to the four-chamber view and the parasagittal view of the right outflow tract. The objective of this study was to define quality criteria for fetal LVOT assessment and to perform a human audit of past and current practices, before and after the implementation of those quality criteria at a large scale. Seven quality criteria were investigated and rated from 0 to 1 during three periods of interest. Files were randomly selected from three centers, and average total and specific scores were calculated. LVOT pictures were present in more than 94.3% of reports. The average quality score was 5.49/7 (95% confidence interval [CI]: 5.36-5.62), 5.91/7 (95% CI: 5.80-6.03), and 5.70/7 (95% CI: 5.58-5.82) for the three centers in the three periods of interest. There was no significant difference following the introduction of the quality criteria, 2017 versus 2020, P = .054. Fetal LVOT images were present in most of ultrasound reports but the introduction of the proposed quality criteria under human supervision seems not associated with a significant change in practice.


Temporal bone trauma and facial paralysis.
Temporal bone trauma includes a wide range of injuries of greater and lesser severity, most of which require the immediate attention of an otolaryngologist. The most common temporal bone injuries encountered in an emergency room setting include longitudinal and transverse fractures of the temporal bone with and without facial paralysis, labyrinthine concussion, foreign bodies in the external canal, penetrating injuries via the external auditory canal, and pressure injuries, including otitic barotrauma, water skiing accidents, blows or slaps to the ear or side of the head, and severe impact noise. A brief but inclusive examination can be performed within the limitations necessarily imposed by an emergency room setting. Cranial nerve screening, balance testing, hearing, and vestibular evaluation can be accomplished with a considerable degree of accuracy. To a large extent, the long term result reflects the quality of the initial examination.


RecJ-like protein from Pyrococcus furiosus has 3'-5' exonuclease activity on RNA: implications for proofreading of 3'-mismatched RNA primers in DNA replication.
Replicative DNA polymerases require an RNA primer for leading and lagging strand DNA synthesis, and primase is responsible for the de novo synthesis of this RNA primer. However, the archaeal primase from Pyrococcus furiosus (Pfu) frequently incorporates mismatched nucleoside monophosphate, which stops RNA synthesis. Pfu DNA polymerase (PolB) cannot elongate the resulting 3'-mismatched RNA primer because it cannot remove the 3'-mismatched ribonucleotide. This study demonstrates the potential role of a RecJ-like protein from P. furiosus (PfRecJ) in proofreading 3'-mismatched ribonucleotides. PfRecJ hydrolyzes single-stranded RNA and the RNA strand of RNA/DNA hybrids in the 3'-5' direction, and the kinetic parameters (Km and Kcat) of PfRecJ during RNA strand digestion are consistent with a role in proofreading 3'-mismatched RNA primers. Replication protein A, the single-stranded DNA-binding protein, stimulates the removal of 3'-mismatched ribonucleotides of the RNA strand in RNA/DNA hybrids, and Pfu DNA polymerase can extend the 3'-mismatched RNA primer after the 3'-mismatched ribonucleotide is removed by PfRecJ. Finally, we reconstituted the primer-proofreading reaction of a 3'-mismatched ribonucleotide RNA/DNA hybrid using PfRecJ, replication protein A, Proliferating cell nuclear antigen (PCNA) and PolB. Given that PfRecJ is associated with the GINS complex, a central nexus in archaeal DNA replication fork, we speculate that PfRecJ proofreads the RNA primer in vivo.


Retrograde intussusception 5 years after Roux-en-Y gastric bypass for morbid obesity.
Small bowel obstruction secondary to intussusception is a rare but important consequence of Roux-en-Y gastric bypass (RYGB). A 37-year old female presented to the emergency department with abdominal pain. She had undergone RYGB 5-years previously for obesity. CT revealed a retrograde jejuno-jejunal intussusception. The intussusceptum was the common jejunal channel and the intussuscepiens was the jejunojejunostomy resulting in obstruction of both the alimentary and biliary limbs. The patient underwent laparotomy, small bowel resection and refashioning of the jejunojejunal anastamosis. We report this case as it highlights both how a delay in diagnosis can occur and the importance of including this complication early in the differential diagnoses of any patient presenting with acute or chronic abdominal pain with a history of bariatric surgery. Retrograde intussusception is more common than previously thought and the incidence may increase as bariatric surgery is performed more frequently worldwide.


Successful hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia type II.
CDA are a group of inherited, rare diseases that are characterized by dyserythropoiesis and ineffective erythropoiesis associated with transfusion dependency in approximately 10% of cases. For these latter patients, the only curative treatment is HSCT. There are very limited data on HSCT experience in this rare disease. Herein, we report a five-yr six-month-old girl with compound heterozygous mutations in SEC23B gene, who was diagnosed to have CDA type II and underwent successful HSCT from her matched sibling donor.


A simple method for calculating the statistical power for detecting a QTL located in a marker interval.
We developed a simple method for calculating the statistical power for detecting a QTL located in an interval flanked by two markers. The statistical method for QTL detection is assumed to be the Haley and Knott's simple regression method of interval mapping. This method allows us to answer one of the fundamental questions in designing a QTL mapping experiment: What is the minimum marker density required to detect a QTL explaining a certain heritable proportion of the phenotypic variance (denoted by h(2)) with a power gamma under a Type I error alpha in an F(2) or other mating designs with a sample size n? Computing the statistical power only requires the ability to evaluate a non-central F-distribution function and the inverse function of this distribution.


Inter-arterial course of the left coronary artery with a commissural origin in a 40-year-old patient with tricuspid atresia post Fontan shunt.
We report a case of an adult male with Tricuspid atresia post Fontan shunt in whom a rare coronary anomaly was demonstrated on Computed Tomography angiography using endoluminal views and volume rendering techniques.


There are two C4 genetic loci and a null allele in the chimpanzee.
Genetic polymorphism in C4 in the chimpanzee was studied by agarose gel electrophoresis of desialated plasma and development of patterns by immunofixation with antiserum to human C4 and by a C4-sensitive hemolytic overlay. In general, immunofixation patterns showed multiple partially overlapping bands of which only the most cathodal had strong hemolytic activity. In analogy to human C4, the latter were designated C4B, whereas those detected by immunofixation which had little hemolytic activity were designated C4A. Chimp C4A and C4B reacted with human and mouse (monoclonal) anti-C4B and human anti-Ch1 but neither reacted with monoclonal anti-C4A or human anti-Ch2, Ch3, Rg1, or Rg2. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the alpha chain of C4B showed a slightly lower apparent relative mass than that of C4A at around Mr 93,000. There were three C4A variants and two C4B variants inherited in families as autosomal codominant traits, as C4A-C4B cosegregating pairs with no detectable crossing-over. These pairs were inherited with chimpanzee leukocyte antigen types C2 and BF variants without detectable crossing-over. Half-null C4 haplotypes with C4B QO were observed in family studies. Nine BF, C2, C4A, C4B allelic haplotypic combinations (complotypes) were identified among presumably unrelated chimpanzees.


Effect of Cinnamic acid and FOLFOX in diminishing side population and downregulating cancer stem cell markers in colon cancer cell line HT-29.
There is a lot of evidence suggesting that a small subset of cancer cells resistant to conventional chemotherapy and radiotherapy and known as cancer stem cells (CSCs) is responsible for promoting metastasis and cancer relapse. Therefore, targeting and eliminating the CSCs could lead to higher survival rates and a better quality of life. In comparison with conventional chemical drugs that may not be effective against CSCs, phytochemicals are strong anti-CSCs agents. The current study examines the effect of 5-fluorouracil plus oxaliplatin (FOLFOX) as a common chemotherapy drug on colorectal cancer as well as the influence of Cinnamic acid (CINN) as a plant-derived phytochemical on colon cancer stem-like cells in HT-29 adenocarcinoma cell line. The anti-proliferative effect of FOLFOX and CINN was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Flow cytometry analysis was used for the identification of side population (SP), CD44, and CD133 positive cells. The expression of OCT4, NANOG, ABCB1, and ALDH1A was assessed by RT-PCR. The FOLFOX and CINN decreased cell viability in certain drug concentrations: IC50 = 5,40 μM oxaliplatin +220 μM 5-fluorouracil, and 13,50 mM for CINN. The CSC-associated markers (OCT4, NANOG, ABCB1, and ALDH1A) and the proportion of cancer stem-like cells (SP cells, CD44, and CD133 positive cells) were downregulated following the treatment of HT-29 adenocarcinoma cell line with IC50 concentrations of FOLFOX and CINN. Our data suggests that CINN, a naturally occurring component, could be more effective than FOLFOX treatment in reducing the cancer stem-like cells and expression of CSC markers from HT-29 colon cancer cells. Graphical abstract .


Mediastinal Masses, Anesthetic Interventions, and Airway Compression in Adults: A Prospective Observational Study.
Central airway occlusion is a feared complication of general anesthesia in patients with mediastinal masses. Maintenance of spontaneous ventilation and avoiding neuromuscular blockade are recommended to reduce this risk. Physiologic arguments supporting these recommendations are controversial and direct evidence is lacking. The authors hypothesized that, in adult patients with moderate to severe mediastinal mass-mediated tracheobronchial compression, anesthetic interventions including positive pressure ventilation and neuromuscular blockade could be instituted without compromising central airway patency. Seventeen adult patients with large mediastinal masses requiring general anesthesia underwent awake intubation followed by continuous video bronchoscopy recordings of the compromised portion of the airway during staged induction. Assessments of changes in anterior-posterior airway diameter relative to baseline (awake, spontaneous ventilation) were performed using the following patency scores: unchanged = 0; 25 to 50% larger = +1; more than 50% larger = +2; 25 to 50% smaller = -1; more than 50% smaller = -2. Assessments were made by seven experienced bronchoscopists in side-by-side blinded and scrambled comparisons between (1) baseline awake, spontaneous breathing; (2) anesthetized with spontaneous ventilation; (3) anesthetized with positive pressure ventilation; and (4) anesthetized with positive pressure ventilation and neuromuscular blockade. Tidal volumes, respiratory rate, and inspiratory/expiratory ratio were similar between phases. No significant change from baseline was observed in the mean airway patency scores after the induction of general anesthesia (0 [95% CI, 0 to 0]; P = 0.953). The mean airway patency score increased with the addition of positive pressure ventilation (0 [95% CI, 0 to 1]; P = 0.024) and neuromuscular blockade (1 [95% CI, 0 to 1]; P < 0.001). No patient suffered airway collapse or difficult ventilation during any anesthetic phase. These observations suggest a need to reassess prevailing assumptions regarding positive pressure ventilation and/or paralysis and mediastinal mass-mediated airway collapse, but do not prove that conventional (nonstaged) inductions are safe for such patients.


Reproductive health care utilization among young mothers in Bangladesh: does autonomy matter?
To examine the linkage between the possible influences of the extent of autonomy on young mothers use of reproductive health care services. This paper used data from the 2007 Bangladesh Demographic Health Survey. The analyses were based on responses of 1,778 currently married women aged 15 to 24 years, living with at least one 0- to 35-month-old child. Utilization of antenatal health services (ANC) services by amount and type of provider, and utilization of delivery assistance according to provider type were used as proxy outcome variables of reproductive health care utilization. Descriptive statistics and multivariate logistic regression methods were employed in the analysis. Approximately one third (31%) of the currently married young women in Bangladesh had a higher level of overall decision-making autonomy. Only 24.0% of the sampled women received sufficient ANC; 54% and 18% received ANC and assisted deliveries from a medically trained provider. respectively. In adjusted models, young women who had a higher level of overall autonomy were more likely to receive sufficient ANC (adjusted odds ratio [AOR], 1.64; 95% confidence interval [CI], 1.17-2.23) and receiving ANC from medically trained provider (AOR, 1.91; 95% CI, 1.42-2.45). Women who had medium overall autonomy were 1.40 times more likely (95% CI, 1.03-1.98) to have deliveries assisted by a medically trained provider than women who had low autonomy. Association between young mother's autonomy and reproductive health care utilization suggest that maternal autonomy needs to be considered as an important sociocultural determinant for the higher utilization of reproductive health care services for young mothers in Bangladesh.


Adenovirus 36 and obesity in children and adolescents.
The primary aim of this study was to assess the relationship between adenovirus 36 (AD36)-specific antibodies and obesity in children. A cross-sectional study of children 8 to 18 years of age was performed. Children were classified according to BMI percentile as nonobese (<95th percentile) or obese (≥95th percentile). The presence of AD36-specific neutralizing antibodies was assessed by using the serum neutralization assay. A total of 124 children (median age: 13.6 years) were studied. Of those children, 46% were nonobese and 54% were obese. AD36 positivity was present in 19 children (15%). The majority of children found to be AD36-positive were obese (15 [78%] of 19 children). AD36 positivity was significantly (P<.05) more frequent in obese children (15 [22%] of 67 children) than nonobese children (4 [7%] of 57 children). Among the subset of children who were obese, those who were AD36-positive had significantly larger anthropometric measures, including weight, BMI, waist circumference, and waist/height ratio. These data support an association of obesity and higher body weight with the presence of neutralizing antibodies to AD36 in children. If a cause-and-effect relationship is established, it would have considerable implications for the prevention and treatment of childhood obesity.


Genetic and environment effects on structural neuroimaging endophenotype for bipolar disorder: a novel molecular approach.
We investigated gene-environment effects on structural brain endophenotype in bipolar disorder (BD) using a novel method of combining polygenic risk scores with epigenetic signatures since traditional methods of examining the family history and trauma effects have significant limitations. The study enrolled 119 subjects, including 55 BD spectrum (BDS) subjects diagnosed with BD or major depressive disorder (MDD) with subthreshold BD symptoms and 64 non-BDS subjects comprising 32 MDD subjects without BD symptoms and 32 healthy subjects. The blood samples underwent genome-wide genotyping and methylation quantification. We derived polygenic risk score (PRS) and methylation profile score (MPS) as weighted summations of risk single nucleotide polymorphisms and methylation probes, respectively, which were considered as molecular measures of genetic and environmental risks for BD. Linear regression was used to relate PRS, MPS, and their interaction to 44 brain structure measures quantified from magnetic resonance imaging (MRI) on 47 BDS subjects, and the results were compared with those based on family history and childhood trauma. After multiplicity corrections using false discovery rate (FDR), MPS was found to be negatively associated with the volume of the medial geniculate thalamus (FDR = 0.059, partial R2 = 0.208). Family history, trauma scale, and PRS were not associated with any brain measures. PRS and MPS show significant interactions on whole putamen (FDR = 0.09, partial R2 = 0.337). No significant gene-environment interactions were identified for the family history and trauma scale. PRS and MPS generally explained greater proportions of variances of the brain measures (range of partial R2 = [0.008, 0.337]) than the clinical risk factors (range = [0.004, 0.228]).


The jury is still out: changes in gastroschisis management over the last decade are associated with both benefits and shortcomings.
Management of gastroschisis has shifted from early primary closure to preformed silo placement and delayed closure. We aimed to identify how closure techniques have changed and how outcomes have been affected. Records of patients undergoing gastroschisis closure at a single institution from 2000 to 2009 were reviewed. Patient characteristics and outcomes were collected and compared among those undergoing primary closure vs preformed silo placement. Outcomes were also compared in an era when primary closure predominated (2000-2002) vs one when primary silo predominated (2003-2009). From 2000 to 2009, 203 patients underwent gastroschisis closure. Primary closure was performed in 50% of patients from 2000 to 2002 vs 12.3% from 2003 to 2009. Preformed silos were placed in 34.7% of patients from 2000 to 2002 vs 84.4% from 2003 to 2009. Patients treated from 2000 to 2002 experienced shorter hospital stays and shorter time to achievement of full enteral nutrition. Patients treated from 2003 to 2009 developed fewer ventral hernias and wound infections and required less ventilator days. Patients undergoing early primary closure developed ventral hernias at higher rates compared with those treated with preformed silos. Intensive care unit stay was longer for patients receiving preformed silos. Change in our management strategy has resulted in prolonged intensive care unit stay and time to full feeds but reduced postoperative hernias and wound infections.


Palmitic acid-modified GnRH-Th epitope peptide immunocastration vaccine (W/O/W adjuvant) can effectively ensure the castration and reduce the smelly smell in boars.
Recent studies have demonstrated the effectiveness of Gonadotropin-releasing hormone (GnRH) in inhibiting testicular growth and development in male animals to achieve castration while improving the meat quality of various livestock species, including cattle, sheep, goats, and pigs. In this research, a GnRH-Th vaccine was synthesized using the Fmoc solid-phase synthesis technique, and the T helper (Th) antigen was modified with palmitic acid to improve its efficacy. The vaccine was then coated with a water-in-oil-in-water adjuvant to improve stability and safety. After passing safety and stability tests, the vaccine was administered to 13-week-old boars. The results showed that it was stable, safe, and effective for up to 15 months. Moreover, the vaccine did not negatively affect the growth rate and body weight of the pigs. The palmitic acid-modified "GnRH-Th epitope peptide immunocastration vaccine (Water-in-Oil-in-Water (W/O/W)) effectively reduced the testosterone concentration and achieved castration. The concentration of androstenone and skatole hormones significantly decreased, leading to improved meat quality in the boars. The boars were then slaughtered at 33 weeks of age, and the results showed that the meat quality of the vaccinated boars was superior to that of the non-vaccinated control group (p < 0.05). This study demonstrated that GnRH can safely and effectively achieve immune castration in boars after coupling T cell epitopes, palmitic acid modification and W-O-W coating. Provide a better method for the further development of GnRH and the realization of animal welfare.


Developmental role of dpp in the gastropod shell plate and co-option of the dpp signaling pathway in the evolution of the operculum.
The operculum is a novel structure in gastropod molluscs. Because the operculum shows notable similarities to the shell plate, we asked whether there were an evolutionary link between these two secretory organs. We found that some of the genes involved in shell-field development are expressed in the operculum, such as dpp and grainyhead, whereas engrailed and Hox1 are not. Specific knockdown of dpp by injection of double-stranded RNA (dsRNA) resulted in malformation of the shell plate. The shell plate was smaller due to failure of activation of cell proliferation in the shell-field margin. The expressions of grainyhead and chitin synthase 1 in the shell field margin were suppressed by dpp-dsRNA. However, matrix secretion was not completely abolished, and the expressions of ferritin, engrailed or Hox1 were not affected by dpp-dsRNA, indicating that dpp is partly involved in the developmental pathway for shell matrix secretion. We also present evidence that dpp performs a key role in operculum development. Indeed, dpp-dsRNA impaired matrix secretion in the operculum as well as expression of grainyhead. Based on these observations that dpp is important for development of both the shell plate and operculum, we conclude that co-option of dpp to the posterior part of the foot contributed to the innovation of the operculum in gastropods.


Intersectional stigma and the arc of intranational migration: experiences of transgender adolescents and women who migrate within Peru.
Migration is recognized as a key determinant of health. Yet, limited research addresses the arc of intranational migration and, even less, the experiences of transgender (trans) adolescents and women migrants and the associated health vulnerabilities. Using intersectional stigma as a theoretical frame, this study seeks to better understand the sexual health vulnerabilities and needs of trans women migrants in Peru. Between October and November 2016, in-depth interviews (n = 14) and two focus groups (n = 20) were conducted in Spanish with trans women in three Peruvian cities. To explore pre- and during migration experiences, focus groups were conducted in Pucallpa and Iquitos, key cities in the Amazon where trajectories often originate. To assess during migration and post-migration experiences, we conducted interviews in Pucallpa, Iquitos, and Lima to better understand processes of relocation. Audio files were transcribed verbatim and analysed via an immersion crystallization approach, an inductive and iterative process, using Dedoose (v.6.1.18). Participants described migration as an arc and, thus, results are presented in three phases: pre-migration; during migration; and post-migration. Intersectional stigma was identified as a transversal theme throughout the three stages of migration. The pre-migration stage was characterized by poverty, transphobia, and violence frequently motivating the decision to migrate to a larger city. Exploitation was also described as pervasive during migration and in relocation. Many participants spoke of their introduction to sex work during migration, as key to economic earning and associated violence (police, clients). Findings advance understandings of intranational migration and forced displacement as key determinants of trans women's health. Dimensions of violence at the intersection of classism and cisgenderism render trans women highly vulnerable at every step of their migratory journeys. Experiences of intranational mobility and relocation were described as uniquely tied to age, intersectional transphobic stigma, engagement in sex work, and multiple forms of violence, which impact and can magnify sexual health vulnerabilities for transgender women in Peru who migrated intranationally.


Clinical stratification improves the diagnostic accuracy of small omics datasets within machine learning and genome-scale metabolic modelling methods.
Recently, multi-omic machine learning architectures have been proposed for the early detection of cancer. However, for rare cancers and their associated small datasets, it is still unclear how to use the available multi-omics data to achieve a mechanistic prediction of cancer onset and progression, due to the limited data available. Hepatoblastoma is the most frequent liver cancer in infancy and childhood, and whose incidence has been lately increasing in several developed countries. Even though some studies have been conducted to understand the causes of its onset and discover potential biomarkers, the role of metabolic rewiring has not been investigated in depth so far. Here, we propose and implement an interpretable multi-omics pipeline that combines mechanistic knowledge from genome-scale metabolic models with machine learning algorithms, and we use it to characterise the underlying mechanisms controlling hepatoblastoma. While the obtained machine learning models generally present a high diagnostic classification accuracy, our results show that the type of omics combinations used as input to the machine learning models strongly affects the detection of important genes, reactions and metabolic pathways linked to hepatoblastoma. Our method also suggests that, in the context of computer-aided diagnosis of cancer, optimal diagnostic accuracy can be achieved by adopting a combination of omics that depends on the patient's clinical characteristics.


Evaluation of Fluorescent Confocal Microscopy for Intraoperative Analysis of Prostate Biopsy Cores.
Diagnosis of prostate cancer is based on histopathological evaluation, which is time-consuming. Fluorescent confocal microscopy (FCM) is a novel technique that allows rapid tissue analysis. To determine if FCM could be used for real-time diagnosis of prostate cancer and evaluate concordance with traditional analysis. From January 2019 to March 2020, 182 magnetic resonance imaging-targeted prostate biopsy cores from 57 consecutive biopsy-naïve men with suspected prostate cancer were taken. These were intraoperatively stained with acridine orange for analysis using FCM (VivaScope; MAVIG, Munich, Germany) and subsequently sent for traditional haematoxylin-eosin histopathological (HEH) examination. Two expert uropathologists analysed the FCM and HEH cores blinded to the counterpart results in a single institution. Agreement between FCM and HEH analysis in terms of the presence of cancer was analysed at biopsy core and region of interest (ROI) levels, considering HEH as the reference test. FCM allowed intraoperative assessment of prostate biopsy cores with strong histopathological evaluation agreement: Cohen's κ for agreement was 0.81 at the biopsy core level and 0.69 for the ROI level. Positive predictive values (85% and 83.78%) and negative predictive values (95.1% and 85.71%) were high at the biopsy core and ROI levels. These initial results are encouraging, but given the single-centre and preliminary nature of the study, further confirmation is required. FCM allowed rapid evaluation of prostate biopsy cores. This technique is feasible and achieves rapid closure with a reliable diagnosis, parallel to the gold standard analysis. Initial results are promising but further studies are needed to validate and define the role of this technique. A novel microscopic technique reduces the time needed to obtain a prostate cancer diagnosis by speeding up biopsy processing. Although the initial results are promising; this development needs to be confirmed in further studies.


Apparently Resistant Hypertension in Polish Hemodialyzed Population: Prevalence and Risk Factors.
The aim of this study was to assess the prevalence, characteristics, and determinants of apparent treatment-resistant hypertension (aTRH) in an unselected large population of patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) throughout the country. A database of 5879 patients (mean age 65.2 ± 14.2 years, 60% of males receiving hemodialysis) was obtained from the biggest provider of hemodialysis in the country. Hypertension and aTRH were defined using pre- or/and post-dialysis BP values. Patients with and without aTRH (non-aTRH) were compared. Using pre- and post-dialysis criteria, hypertension was diagnosed in 90.7% and 89.1% of subjects, respectively. According to pre- and post-dialysis blood pressure criteria, aTRH incidences were 40.9% and 38.4%, respectively. The hypertensive patients with aTRH versus non-aTRH were younger, had a higher rate of cardiovascular disease, lower dialysis vintage, shorter time on dialysis, higher eKt/V, higher ultrafiltration, higher pre- and post-dialysis BP and HR, and higher use of antihypertensive drugs. Factors that increase the risk of aTRH according to both pre- and post-dialysis BP criteria were age-OR 0.99 [0.98-0.99] and 0.99 [0.98-0.99], the history of CVD 1.26 [1.08-1.46] and 1.30 [1.12-1.51], and diabetes 1.26 [1.08-1.47] and 1.28 [1.09-1.49], adjusted OR with 95% CI. In the real-life world, as much as 40% of HD patients may have aTRH. In ESKD HD patients, aTRH seems to be multifactorial, influenced by patient-related rather than dialysis-related factors. Various definitions of aTRH preclude easy comparisons between studies.


Significant Zr isotope variations in single zircon grains recording magma evolution history.
Zircons widely occur in magmatic rocks and often display internal zonation finely recording the magmatic history. Here, we presented in situ high-precision (2SD <0.15‰ for δ94Zr) and high-spatial-resolution (20 µm) stable Zr isotope compositions of magmatic zircons in a suite of calc-alkaline plutonic rocks from the juvenile part of the Gangdese arc, southern Tibet. These zircon grains are internally zoned with Zr isotopically light cores and increasingly heavier rims. Our data suggest the preferential incorporation of lighter Zr isotopes in zircon from the melt, which would drive the residual melt to heavier values. The Rayleigh distillation model can well explain the observed internal zoning in single zircon grains, and the best-fit models gave average zircon-melt fractionation factors for each sample ranging from 0.99955 to 0.99988. The average fractionation factors are positively correlated with the median Ti-in-zircon temperatures, indicating a strong temperature dependence of Zr isotopic fractionation. The results demonstrate that in situ Zr isotope analyses would be another powerful contribution to the geochemical toolbox related to zircon. The findings of this study solve the fundamental issue on how zircon fractionates Zr isotopes in calc-alkaline magmas, the major type of magmas that led to forming continental crust over time. The results also show the great potential of stable Zr isotopes in tracing magmatic thermal and chemical evolution and thus possibly continental crustal differentiation.


Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide.
Although recent studies indicate that renal ischemic preconditioning (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise protective mechanism remains unclear. In the current study, we investigated whether early IPC could upregulate hypoxia inducible transcription factor-1α (HIF-1α) expression and could reduce endoplasmic reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric oxide (NO) production would abolish these protective effects. Kidneys of Wistar rats were subjected to 60 min of warm ischemia followed by 120 min of reperfusion (I/R group), or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to intravenously injection of NG-nitro-L-arginine methylester (L-NAME, 5 mg/kg) 5 min before IPC (L-NAME+IPC group). The results of these experimental groups were compared to those of a sham-operated group. Sodium reabsorption rate, creatinine clearance, plasma lactate dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde (MDA), HIF-1α and nitrite/nitrate were determined. In addition, Western blot analyses were performed to identify the amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress parameters. IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallelly, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1α levels as compared to I/R group. Moreover, our results showed that IPC increased the relative amounts of glucose-regulated protein 78 (GRP78) and decreased those of RNA activated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptor-associated factor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished these beneficial effects of IPC against renal I/R insults. These findings suggest that early IPC protects kidney against renal I/R injury via reducing oxidative and ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production contributing thus to HIF-1α stabilization. The beneficial impact of IPC was abolished when NO production is inhibited before IPC application.


Chronic viral hepatitis C, oxidative stress and the coagulation/fibrinolysis system in haemodialysis patients.
The aim of the present study was to establish whether the presence of chronic viral hepatitis (PVH) could be implicated in the elevation of oxidative stress (SOX) and haemostasis system in haemodialysis (HD) patients. In HD patients with and without PVH and in controls we compared the markers of: coagulation pathway- tissue factor (TF) and its inhibitor (TFPI), prothrombin fragment F (1+2) (F (1+2)); fibrinolysis: tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR), plasminogen activator inhibitor 1 (PAI-1), plasmin/antiplasmin complexes (PAP); and a marker of SOX-Cu/Zn superoxide dismutase (Cu/Zn SOD) levels. Patients, particularly those with PVH, showed a significant increase in the markers of the coagulation, fibrinolysis and oxidative status as compared to controls. All parameters of coagulation/fibrinolysis system were directly associated with the PVH and Cu/Zn SOD levels, and there was a relationship between the PVH and Cu/Zn SOD levels. Multivariable analysis showed that PVH and increased SOX were identified as independent variables significantly associated with the disturbances of coagulation/fibrinolysis system in these patients. We concluded that PVH is a novel determinant of the increased oxidative stress as well as the disturbances of coagulation/fibrinolysis system in haemodialysis patients.


Agarose encapsulation of islets of Langerhans: reduced toxicity in vitro.
The physical and chemical properties of agarose have been exploited for encapsulation of islets of Langerhans. Formation of microcapsules by extrusion of a hydrophilic polymer (agarose) into a hydrophobic solution created an interface to which an immunoprotective membrane could be polymerized. The substances and procedure used were devoid of cellular toxicity. Islet function in vitro was found to be normal.


Effects of lowering dialysate sodium on carotid artery atherosclerosis and endothelial dysfunction in maintenance hemodialysis patients.
Our aim in this study was to examine the effects of low-sodium dialysate on carotid artery atherosclerosis, endothelial dysfunction, and blood pressure (BP) in maintenance hemodialysis (HD) patients. After baseline measurements were obtained, the dialysate sodium concentration was reduced from 140 to 137 mEq/L. Carotid artery intima-media thickness (CIMT) and flow-mediated dilatation (FMD%) were measured before and after 6 months of HD with low-sodium dialysate. Interdialytic weight gain (IDWG), pre- and post-dialysis BP, and dialysis-related symptoms were monitored during the study. Fifty-two patients were enrolled, and 41 patients completed the study. Twenty-one patients had hypertension and were receiving antihypertensive medications. The average number of antihypertensive drugs per patient was 1.9±0.8. There was no significant reduction in BP at the end of the study, but the average number of antihypertensive drugs was reduced to 1.2±0.4 (P<0.001). There were significant improvements in CIMT (P=0.003) and FMD (P<0.001) with low-sodium HD. The IDWG decreased significantly during the low-sodium dialysate treatment (P<0.001). However, hypotensive episodes and cramps were more frequent during the study period. Our study demonstrated that the lowering of dialysate sodium concentration reduced CIMT, improved FMD, and provided better control of IDWG and BP, but increased the incidence of dialysis-related symptoms.


Differential induction of prostaglandin E2-dependent and -independent immune suppressor cells by tumor-derived GM-CSF and M-CSF.
Both prostaglandin E2 (PGE2)-dependent (indomethacin-sensitive) and PGE2-independent (indomethacin-insensitive) suppressor cell activities that inhibited mitogenic T cell blastogenesis appeared in the bone marrow and spleen of mice on days 20 to 30 following transplantation of NFSA fibrosarcoma molecularly expressing mRNA for both macrophage (M) and granulocyte-macrophage (GM) colony-stimulating factors (CSFs). The present study was done to characterize the two different suppressor cells isolated from NFSA tumor-bearing mice and to verify a role of CSFs in the induction of suppressor cells in vitro. Whereas PGE2-releasing suppressor cells were found in bone marrow and spleen cells isolated from tumor-bearing mice, indomethacin-insensitive suppressor cells in both tissues were localized predominantly in adherent cell fractions. An increase in Mac-1+ and Mac-2+ spleen cell populations with two to three times larger cell volumes was observed, and both showed strong PGE2-releasing capacity and indomethacin-sensitive suppressor cell activity. However, after elimination of Mac-1+ or Mac-2+ cells, bone marrow cells still showed higher PGE2-releasing capacity and indomethacin-sensitive suppressor activity. The in vitro cultures of normal bone marrow and spleen cells with NFSA cell conditioned medium (NFSA-CM) induced heterogeneous mixtures of indomethacin-sensitive and - insensitive suppressor cells like those observed in cultures with the combination of M-CSF and GM-CSF. However, cultures with either GM-CSF or M-CSF resulted in the induction of indomethacin-sensitive suppressor cells by GM-CSF and of indomethacin-insensitive suppressor cells by M-CSF. In addition, NFSA-CM pretreated with anti-GM-CSF antibody induced indomethacin-insensitive suppressor cells in in vitro cultures of bone marrow and spleen cells. These results suggest that two distinctly different suppressor cells developed under hemopoiesis of myelomonocytic lineage cells are regulated differentially by the two macrophage growth factors, M-CSF and GM-CSF.


The incidence of recurrent venous thromboembolism in carriers of factor V Leiden is related to concomitant thrombophilic disorders.
The duration of anticoagulant treatment after a first episode of venous thromboembolism primarily depends on the risk of recurrence. Variability of recurrence rates in factor (F) V Leiden carriers may be due to concomitant thrombophilic disorders. A retrospective study was performed in 329 FV Leiden carriers with a history of venous thromboembolism (262 probands, 67 relatives). The annual rate of first recurrence was estimated in relatives. The contribution of concomitant thrombophilic disorders to the recurrence rate was evaluated in probands and relatives by a nested case--control analysis in 105 matched pairs of carriers either with or without recurrence. The overall annual recurrence rate was 2.3 per 100 patient-years. The adjusted risk of recurrence for concomitant thrombophilic disorders was: 9.1 (1.3-62.8) for the FII mutation; 1.0 (0.2-4.9) for homozygosity for FV Leiden; 1.5 (0.2-9.5) for inherited deficiencies of protein C or S; 1.8 (0.7-4.9) for FVIII coagulant activity (FVIII:C) levels >122%; 5.4 (1.6-18.6) for fasting homocysteine levels >15.2 micromol/l; and 4.4 (1.0-18.7) for loading homocysteine levels >45.8 micromol/l. Of these disorders, only the FII mutation and hyperhomocysteinaemia significantly increased the risk of recurrence in FV Leiden carriers. The estimated recurrence rate ranged from 0.45 per 100 patient--years after a secondary first event in the absence of concomitant disorders to 4.8 per 100 patient-years when a spontaneous first event was combined with concomitant disorders. Our study provides supportive evidence that the incidence of recurrent venous thromboembolism in heterozygous FV Leiden carriers depends on the concomitance of other thrombophilic disorders, in addition to whether the first thrombotic event occurred spontaneously.


In situ hybridization of GnRH mRNA in the rat and the mink hypothalamus using biotinylated synthetic oligonucleotide probes.
The cellular localization of GnRH messenger RNA (mRNA) in the rat and the mink hypothalamus has been examined using a newly developed highly sensitive non-radioactive in situ hybridization procedure. Synthetic oligonucleotides labeled by addition of a biotin-21-dUTP tail at their 3' end can be used to detect GnRH mRNA in both species. Streptavidin-alkaline phosphatase revealed with nitroblue tetra-zolium-bromo-chloro-indolyl-phosphate as substrate makes possible detection of the biotinylated oligonucleotides. In the rat, our findings confirm results previously obtained using synthetic radioactive probes, and demonstrate the potency of and interest in using biotinylated oligonucleotides to identify related sequences of bases in tissues. The principle advantages include rapid signal detection, excellent spatial resolution, and low background. In the mink, the in situ hybridization method clearly confirms the characterization of GnRH-producing cells and also allows detection of GnRH cell bodies in conditions in which they are not detected by immunohistochemistry. Adaptation of the in situ hybridization to the detection of GnRH mRNA in species like the mink which shows seasonal reproductive activity is a crucial step. This method offers a new approach to problems as fundamental as changes in gene expression depending on photoperiod or under a variety of experimental conditions.


Osteointegration of a Biocomposite Suture Anchor After Arthroscopic Shoulder Labral Repair.
To evaluate osteoconductivity of a poly-L-lactide co-glycolide (PLG)-calcium sulfate (CS)-β-tricalcium phosphate (β-TCP) biocomposite suture anchor after arthroscopic shoulder labral repair. The subjects of this study were patients who participated in a clinical trial for acquisition of marketing approval of a PLG-CS-β-TCP biocomposite anchor in Japan. They underwent arthroscopic labral repair using the anchor, and computed tomographic (CT) images of the glenoid were obtained 2 years after surgery. Osteoconductivity at the anchor sites was evaluated with the CT images using the established ossification quality score. Shoulder function scores including the Rowe score and Japanese Shoulder Society shoulder instability score were also assessed 2 years after surgery. CT images and functional scores were obtained from 37 patients, comprising 29 men and 8 women with a mean age of 29 years (range, 25-33 years) at surgery. A total of 148 anchors were implanted in the 37 shoulders. Osteoconductivity was seen in 133 of 148 anchor sites (90.0%) 2 years after implantation. No significant differences in osteoconductivity were found by anchor diameter or position. The Rowe score significantly improved from 39.9 points (95% confidence interval [CI], 33.8-45.9 points) preoperatively to 96.6 points (95% CI, 95.1-98.1 points) at 2 years postoperatively (P < .001). The Japanese Shoulder Society shoulder instability score also significantly improved, from 63.1 points (95% CI, 58.4-67.7 points) preoperatively to 96.3 points (95% CI, 94.7-97.8 points) at 2 years postoperatively (P < .001). Biocomposite suture anchors made of PLG, CS, and β-TCP exhibited some osteoconductivity 2 years after arthroscopic labral repair, as well as good clinical outcomes. Level IV, therapeutic case series.


Analysis of Patient-reported Outcomes Measures Used in Lumbar Fusion Surgery Research for Degenerative Spondylolisthesis.
Meta-analyses. This study aims to document the most common Patient-reported Outcome Measures (PROMs) used to assess lumbar fusion surgery outcomes and provide an estimate of the average improvement following surgical treatment. As health care institutions place more emphasis on quality of care, accurately quantifying patient perceptions has become a valued tool in measuring outcomes. To this end, greater importance has been placed on the use of PROMs. This is a systemic review and meta-analysis of randomly controlled trials published between 2014 and 2019 assessing surgical treatment of degenerative spondylolisthesis. A fixed effect size model was used to calculate mean difference and a 95% confidence interval (95% CI). Linear regression was used to calculate average expected improvement, adjusted for preoperative scores. A total of 4 articles (7 study groups) were found for a total of 444 patients. The 3 most common PROMs were Oswestry Disability Index (ODI) (n=7, 100%), Short-Form-12 or Short-Form-36 (SF-12/36) (n=4, 57.1%), and visual analog scale-back pain (n=3, 42.8%). Pooled average improvement was 24.12 (95% CI: 22.49-25.76) for ODI, 21.90 (95% CI: 19.71-24.08) for SF-12/36 mental component score, 22.74 (95% CI: 20.77-24.71) for SF-12/36 physical component score, and 30.87 (95% CI: 43.79-47.97) for visual analog scale-back pain. After adjusting for preoperative scores, patients with the mean preoperative ODI (40.47) would be expected to improve by 22.83 points postoperatively. This study provides a range of expected improvement for common PROMs used to evaluate degenerative spondylolisthesis with the goal of equipping clinicians with a benchmark value to use when counseling patients regarding surgery. In doing so, it hopes to provide a comparison point by which to judge individual patient improvement. Level II.


ABUNDANCE AND MULTIMODAL VISIBILITY OF SOFT DRUSEN IN EARLY AGE-RELATED MACULAR DEGENERATION: A Clinicopathologic Correlation.
To determine the abundance and multimodal visibility of drusen and basal linear deposit (BLinD) in early age-related macular degeneration. A 69-year-old white man was imaged by color fundus photography and red free photography, fundus autofluorescence, and optical coherence tomography. From en face images, we determined the drusen field, drusen area, and equivalent diameters of individual drusen. From high-resolution light-microscopic histology (6 months after the last clinic visit), we determined the area of drusen, BLinD, and pre-BLinD in a subretinal pigment epithelium-basal lamina lipid field. In right and left eyes, respectively, BLinD covered 40% and 46% of the lipid field, versus 21% and 14% covered by drusen. The lipid field was covered 60% to 61% by Drusen + BLinD and 65% to 72% by BLinD + pre-BLinD. In the left eye, the drusen area on color fundus photography (0.18 mm) and red free (0.28 mm) was smaller than the drusen area on histology (1.16 mm). Among drusen confirmed by optical coherence tomography, 55.1% and 56.6% were observed on red free and fundus autofluorescence, respectively. Basal linear deposit covered 1.9 and 3.4-fold more fundus area than soft drusen, silently increasing progression risk. Improved visualization of BLinD and readouts of the retinal pigment epithelium health over lipid will assist population surveillance, early detection, and trial outcome measures.


Overweight in school-aged children associated with emotional and behavioral difficulties: results from a national sample.
To determine whether there is an association between perceived pediatric overweight and emotional/behavioral difficulties among children ages 4 to 17 years in the United States. A cross-sectional study Interview of an adult knowledgeable about a child's emotional and physical health. All statistical analyses were completed using SPSS 17.0. A total of 7096 noninstitutionalized children aged 4 to 17 years identified in the 2007 National Health Interview Survey. Included in the 2007 National Health Interview Survey were 7096 noninstitutionalized children aged 4 to 17 years. After controlling for age, gender, race, poverty status, education of mother, family structure, and health status, this study found that 7.4% of the children appeared to be overweight and 5.2% had emotional/behavioral difficulties. It also found that caregivers who indicated that their child had a problem with being overweight were more likely to report that the child experienced emotional/behavioral difficulties compared to caregivers who did not report perceived overweight in their child. Characteristics of the children most frequently reported to be overweight included Hispanic race, older children (ages 15-17 years), and those with higher poverty rates and poorer health status. The continual increase in pediatric overweight and associated emotional/behavioral difficulties suggests a need for replicable interventions that teach child caregivers to recognize and prevent overweight among vulnerable populations.


A cadaver study to measure the adult glottis and subglottis: defining a problem associated with the use of double-lumen tubes.
To test the hypothesis that the adult cricoid diameter is the same or less than that of the glottis. Prospective. A city mortuary. Adult cadavers undergoing autopsy. After removal of the organs, the trachea was opened above the first ring to allow access to the cricoid from below, and the cricothyroid membrane was cut so that passage of measuring sounds through the vocal cords from above could be confirmed. In 79 male and 55 female cadavers, the largest of a graduated series of cylindrical sounds that the cricoid ring would accommodate was noted. Then the biggest size possible that could pass through the glottis was measured. Height and weight were recorded. In 68% of males and 76% of females, glottic diameter was greater than subglottic; in all other cases, it was the same. In none was it smaller. Correlation between height and cricoid diameter was 0.24 for male cadavers and 0.21 for female cadavers. Regression analysis showed females to average a cricoid diameter 3.5 mm less than males of the same height. The ruling diameter of the adult larynx is not the glottis but the cricoid ring. Its correlation with height is extremely poor, and it averages 3.5 mm less in females than males of the same height. These findings are important for thoracic anesthesiologists.


[Epidemiology of infantile asthma in the Le Havre region].
Prevalence of asthma is influenced by environmental factors which may be different from area to area. A cross-sectional epidemiological survey was carried out among 1,395 children attending primary schools in the city of Le Havre and the canton of Fécamp (Haute-Normandie). Questionnaires including data about the disease, family history, environmental and socio-economic factors were completed by the school physician in presence of the parents. Prevalence rate of asthma calculated from 1,193 questionnaires was 7.8%. The logistic regression curves pointed out four risk factors: family history of asthma (odds ratio: 2.52) or hay fever (OR: 1.98), atopic dermatitis (OR: 3.96), and parental smoking (OR: 1.79). Sex, socioeconomic status of parents, type of housing, presence of pets in the house were not related to prevalence of asthma. Frequency of cough during the day was only significantly different between both areas. The high level of school absence (21.1%) and frequency of hospitalizations for acute asthma (20.4%) should lead health professionals and educators to improve management of asthma in these areas.


Epidemiology of hepatitis D virus (HDV) infection in an urban area of northern Italy.
The introduction of vaccination against hepatitis B initially reduced the number of HBV (hepatitis B virus) and HDV (hepatitis delta virus) infections, but the decreasing trend of HDV infection seems to have stopped. The aim of this study was to assess the prevalence of HDV infection in the general population living in the catchment area of Legnano Hospital in northern Italy. Of the 22,758 subjects tested in 2007-2008, the 488 who were HBsAg (hepatitis B surface antigen)-positive [including 107 (21.9%) of non-Italian origin] were subsequently tested for anti-HDV antibodies. Of the 488 subjects who tested positive for HBsAg, 24 (4.9%) were anti-HDV positive, all aged between 30 and 60 years. The difference in prevalence between males (7.1%) and females (1.9%) was statistically significant (p < 0.05), but not that between Italian (5.0%) and non-Italian patients (4.7%). The differences in anti-HDV seropositivity between the patients with acute (0%) and chronic infections (6.3%), and between the incident (2.5%) and prevalent cases (7.4%), were not statistically significant, but there was a significant difference (p < 0.01) between those with asymptomatic (2.1%) and clinically symptomatic infections (10.3%). Intravenous drug abuse was the main source of infection. In the catchment area of our hospital, the prevalence of HDV infection does not seem to be due to patients of non-Italian origin, but to Italian patients who are not vaccinated against HBV and who survived the HDV epidemic of the 1970s and 1980s. Nevertheless, the increase in the number of immigrants from non-EU countries in recent years is soon likely to lead to a change in the epidemiology of HDV.


Cerebral amino acid levels and uptake in rats after portocaval anastomosis: I. Regional studies in vitro.
Uptake of various amino acids was studied in slices from brain regions of rats four weeks after portocaval anastomosis. No differences of the inulin compartment were observed between control and experimental animals. After 60-minutes incubation, uptake showed an overall pattern of diminution. This was more evident for some amino acids: valine, methionine, and lysine exhibited a lowering of about 30%, which was fairly uniform in the four tested regions; others showed a regional decrease-- alanine in pons-medulla, phenylalanine in cerebellum, histidine and GABA in mesodiencephalon. This decrease did not seen to be related to transport classes. The restricted entry of amino acids into brain cells in portocaval encephalopathy is somewhat difficult to explain; a decreased rate of protein synthesis may be of some importance, but other factors, such as a "carrier" impairment, effects on release and on amino acid metabolism, may also be involved.


Optimal foraging: the difficulty of exploiting different feeding strategies simultaneously.
The foraging efficiency of a visually feeding fish, perch (Perca fluviatilis) was studied on two prey species (Daphnia magna and Chaoborus obscuripus) presented either separately or combined. It is shown that when both prey species are present, the foraging efficiency of the predator is reduced. This is due to the predator's inability to simultaneously cope with prey species with different anti-predatory behaviour. In the mixed-meal experiment the predator captured both prey species in equal proportions in disagreement with optimal foraging models assuming that handling time and encounter rate for a prey species are independent of other prey species. The results are, however, in agreement with optimal foraging models assuming that handling time and encounter rate are influenced by short time learning.


Small molecule pinocytosis and clathrin-dependent endocytosis at the intestinal brush border: Two separate pathways into the enterocyte.
Pinocytosis at the small intestinal brush border was studied in postweaned porcine cultured mucosal explants, using the fluorescent polar probes Alexa hydrazide (AH, MW 570), Texas red dextran (TRD, MW ~ 3000), and Cascade blue dextran (CBD, MW ~ 10,000). Within 1 h, AH appeared in a string of subapical punctae in enterocytes, indicative of an ongoing constitutive pinocytosis. By comparison, TRD was taken up less efficiently into the same compartment, and no intracellular labeling of CBD was detectable, indicating that only small molecules are pinocytosed from the postweaned gut lumen. AH remained in the terminal web region in EEA-1-positive endosomes ("TWEEs") for at least 2 h, implying that the pinocytic uptake does not proceed towards a transcytic pathway. Like AH, cholera toxin B subunit (CTB) was readily internalized, but the two probes appeared in completely non-overlapping subapical compartments, indicating the existence of two different uptake mechanisms operating simultaneously at the brush border. CTB is internalized by clathrin-dependent receptor mediated endocytosis, but surprisingly the toxin also caused a rapid disappearance from the apical cell surface of two major brush border enzymes, alkaline phosphatase and aminopeptidase N, demonstrating the disruptive effect of this pathway. By immunofluorescence, caveolin-1 was hardly detectable in enterocytes, arguing against a caveolae-mediated uptake of AH, whereas the pinocytosis/phagocytosis inhibitors dimethyl amiloride and cytochalasin D both arrested AH uptake. We propose that the constitutive pinocytic mechanism visualized by AH contributes to maintenance of membrane homeostasis and to enrich the contents of lipid raft constituents at the brush border.


Recurrent bacterial pneumonia: a contemporary perspective.
Numerous clinical disorders predispose to "recurrent bacterial pneumonia." Identification and treatment of some of these predisposing conditions will reduce associated morbidity, mortality, and health care expenditures. In young adults these disorders include cystic fibrosis, the immotile-cilia syndrome, Young's syndrome, pulmonary sequestration, and bronchiectasis. Disorders enhancing recurrent bacterial pneumonia in older adults include chronic obstructive lung disease, bronchial obstruction, specific malignancies, hypogammaglobulinemia, alcoholism, neurologic diseases, and esophageal abnormalities.


Macroscopic Extranodal Extension In Oral Squamous Cell Carcinoma-A Subgroup With Poor Survival.
Oral cancer portends a significant cause of morbidity and mortality worldwide. Cervical lymph node metastasis with extranodal extension (ENE) is associated with a poor prognosis. There has been accumulating evidence regarding the extent of ENE to be associated with prognosis and survival. This observational study was performed to analyze the prognostic implication of macroscopic and microscopic ENE in metastatic cervical lymph nodes of oral cavity cancer patients. A total of 92 oral cavity cancer patients with pathologically detected ENE were included in this study. Both the groups (macroscopic and microscopic ENE) were compared in terms of overall survival and disease-free survival by using Kaplan -Meier. The pattern of failure was determined by Fischer's exact test. Univariate and multivariate analyses were calculated to determine the significant risk factors of death. The 2 years of disease-free survival and overall survival rates for the whole cohort were 51.2% and 53.9% respectively. The 2-year survival rate for the microscopic group (≤2 mm) and macroscopic (>2 mm) was 72.6% and 0% respectively, while the distal failure rate in microscopic ENE group and macroscopic ENE group was 22.22% and 44.83% respectively (p-value = 0.026). Macroscopic ENE (>2 mm) in oral cavity squamous cell cancer represents an aggressive entity with early regional and distant failure as compared to microscopic ENE (≤2 mm). Thus, macroscopic ENE (>2 mm) warrants a distinct subgroup with special consideration for intensification of treatment. 3 Laryngoscope, 133:588-593, 2023.


Transdermal drug transport and metabolism. II. The role of competing kinetic events.
The steady-state flux and skin tissue distribution of a topically applied diester of salicylic acid was measured in vitro in the presence and absence of an esterase inhibitor. When compared with data obtained previously under in vivo conditions, the results presented here provide insight into the role of competing diffusional and hydrolytic events in the delivery and distribution of topically applied drugs. Furthermore, these results, when combined with a theoretical analysis of topical drug delivery and metabolism, suggest that the differences in delivery and drug distribution seen under in vitro conditions are related to both altered drug removal and altered hydrolysis rates.


A two-phase fluid model for epidemic flow.
We propose a new mathematical and computational modeling framework that incorporates fluid dynamics to study the spatial spread of infectious diseases. We model the susceptible and infected populations as two inviscid fluids which interact with each other. Their motion at the macroscopic level characterizes the progression and spread of the epidemic. To implement the two-phase flow model, we employ high-order numerical methods from computational fluid dynamics. We apply this model to simulate the COVID-19 outbreaks in the city of Wuhan in China and the state of Tennessee in the US. Our modeling and simulation framework allows us to conduct a detailed investigation into the complex spatiotemporal dynamics related to the transmission and spread of COVID-19.


Transport of the Tumen River water to the Far Eastern Marine Reserve (Posyet Bay) based on in situ, satellite data and Lagrangian modeling using ROMS current velocity output.
We study physical mechanisms of the Tumen River water transport in the area of the Posyet Bay (Peter the Great Bay, Sea of Japan). This study is based on the satellite and in situ measurements, and numerical simulation of advection of river water by the current velocity simulated by Regional Ocean Model System (ROMS). The importance of this study is in identification of the reasons of the transport of pollutants into the area of the Far Eastern Marine Reserve. The results of the study showed that such reasons are wind currents and mesoscale cyclonic eddies. These eddies were originally detected on satellite imagery and CTD and bio-optical measurements. The anomalies in the form of spots of the chlorophyll a (CHL) increased concentration were detected on satellite images in fall 2009. The oceanographic sections of CTD and bio-optical measurements through the anomalies show that they are cyclonic eddies. These eddies consist of two cores - upper and lower. The upper core is filled with river waters with low salinity, high values of CHL and colored dissolved organic matter content (CDOM). The lower core is filled with cold saline waters. The ROMS results show that eddies are generated as a result of symmetrical and centrifugal instabilities.


[Models for primary care and mental health collaboration in the care of people with depression: main results and methodological challenges of a systematic overview].
Weaknesses in the collaboration between Primary Care (PC) and Mental Health (MH) are a relevant problem in the care of depressed patients. It is necessary to analyse and appraise the existing models of collaboration to assess their applicability to the Spanish Health System. The aim of this study is to know the main characteristics of the different models of collaboration between PC and MH in the care of patients with depression and the quality of their effectiveness evidence. Systematic overview of secondary studies published from 2001 to 2010 in MEDLINE, PsycINFO, Embase, LILACS, IBECS, IME and The Cochrane Library. Assessment of reviews applying the AMSTAR tool. Approximative synthesis of the quality of evidences. A total of 69 studies were assessed. Quality of evidences is generally low or inconclusive due to the great variability among contexts and the methodological weaknesses. The most effective strategies integrate interventions for assigning responsibility for patient follow-up, redesigning management and communication/information sharing. Overviews of secondary studies on collaborative models facilitate access to published evidence, but entail important methodological challenges. The quality of evidences on effectiveness of PC-MH collaboration models in depression care is mainly low or inconclusive, and the more simplified are the analysis of components, processes and implementation conditions, the less meaningful and applicable they are.


Insights into the mechanism of histamine synthesis and recycling disruption induced by exposure to CdO NPs in the fruit fly (Drosophila melanogaster).
Exposure to a sublethal concentration of CdO nanoparticles impairs the vision of the fruit fly (Drosophila melanogaster) by disrupting histamine (HA) synthesis and recycling mechanisms. To gain more insights, we measured HA titer using HPLC in CdO NP-treated vs. non-treated adults in the current study and found that CdO NPs caused an increase in the level of HA in the head and the decapitated body. We asked whether HA accumulation (increase) is a response of photoreceptors or CNS histaminergic neurons, and whether there is any difference in the expression levels of HA recycling and transport encoding genes (Lovit, CarT, Ebony, Tan, BalaT) between the adult fly head and decapitated body that could explain this HA accumulation. We used GAL4/UAS system tool with three GAL4 drivers: ubiquitous tubP-GAL4, nervous system driver (elav Gal4), and compound eye drivers (sev Gal4 and GMR Gal4) to silence HA synthesis in site specific manner followed by detecting the expression level of genes involved in HA recycling and transport in both the heads and the decapitated bodies of CdO treated and non-treated flies. We found an increase in Lovit expression in the heads of treated adults, which is responsible for HA loading into synaptic vesicles and release from photoreceptors, as well as a decrease in catalytic enzymes involved in HA recycling, which leads to HA accumulation without increasing the real signal. To conclude, both photoreceptors and CNS histaminergic neurons are responsible for the increase in HA in CdO NP-treated flies, but through different mechanisms. Our results provide more insights on the underlying molecular mechanism of vision impairment because of nano-sized cadmium particles exposure.