Elasticity-based development of functionally enhanced multicellular 3D liver encapsulated in hybrid hydrogel.
Current in vitro liver models provide three-dimensional (3-D) microenvironments in combination with tissue engineering technology and can perform more accurate in vivo mimicry than two-dimensional models. However, a human cell-based, functionally mature liver model is still desired, which would provide an alternative to animal experiments and resolve low-prediction issues on species differences. Here, we prepared hybrid hydrogels of varying elasticity and compared them with a normal liver, to develop a more mature liver model that preserves liver properties in vitro. We encapsulated HepaRG cells, either alone or with supporting cells, in a biodegradable hybrid hydrogel. The elastic modulus of the 3D liver dynamically changed during culture due to the combined effects of prolonged degradation of hydrogel and extracellular matrix formation provided by the supporting cells. As a result, when the elastic modulus of the 3D liver model converges close to that of the in vivo liver (≅ 2.3 to 5.9 kPa), both phenotypic and functional maturation of the 3D liver were realized, while hepatic gene expression, albumin secretion, cytochrome p450-3A4 activity, and drug metabolism were enhanced. Finally, the 3D liver model was expanded to applications with embryonic stem cell-derived hepatocytes and primary human hepatocytes, and it supported prolonged hepatocyte survival and functionality in long-term culture. Our model represents critical progress in developing a biomimetic liver system to simulate liver tissue remodeling, and provides a versatile platform in drug development and disease modeling, ranging from physiology to pathology. We provide a functionally improved 3D liver model that recapitulates in vivo liver stiffness. We have experimentally addressed the issues of orchestrated effects of mechanical compliance, controlled matrix formation by stromal cells in conjunction with hepatic differentiation, and functional maturation of hepatocytes in a dynamic 3D microenvironment. Our model represents critical progress in developing a biomimetic liver system to simulate liver tissue remodeling, and provides a versatile platform in drug development and disease modeling, ranging from physiology to pathology. Additionally, recent advances in the stem-cell technologies have made the development of 3D organoid possible, and thus, our study also provides further contribution to the development of physiologically relevant stem-cell-based 3D tissues that provide an elasticity-based predefined biomimetic 3D microenvironment.


The landscape of immune checkpoint inhibitor plus chemotherapy versus immunotherapy for advanced non-small-cell lung cancer: A systematic review and meta-analysis.
Lung cancer is the leading cause of cancer-related deaths worldwide and the prognosis remains poor. The recent introduction of the immune checkpoint inhibitor (ICI), or plus chemotherapy, both resulted in the survival benefit for patients with advanced non-small-cell lung cancer (NSCLC), but it remains unanswered which is superior. The current study aimed to estimate the comparative efficacy and safety of ICI-chemotherapy versus ICI-monotherapy in advanced NSCLC. Studies were identified by searching PubMed, Embase, and Cochrane library. The randomized controlled trials (RCTs) that ICI monotherapy or ICI plus chemotherapy compared with chemotherapy in NSCLC were included with available primary endpoints of progression-free survival (PFS), overall survival (OS), objective response rate, or treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. A total of 20 RCTs involving 12,025 patients with NSCLC were included. Both ICI-monotherapy and ICI-chemotherapy resulted in significantly prolonged survival compared to chemotherapy and the former led to significantly longer PFS. The magnitude of survival benefits appeared to be greatest among those treated with pembrolizumab plus platinum-based chemotherapy (OS, 0.56; PFS, 0.54). Additionally, OS and PFS advantages of ICI therapies were observed in patients with NSCLC with low or high programmed cell death 1 ligand 1 (PD-L1) expression level, but not in intermediate PD-L1 TPS. Pembrolizumab plus platinum-based chemotherapy was recommended as the optimal first-line therapy for advanced patients with NSCLC. Additionally, PD-L1 alone is not recommended as an adequate molecular biomarker to identify eligible patients for routine clinical practice in immunotherapy.


Four years experience of first-trimester nuchal translucency screening for fetal aneuploidies with increasing regional availability.
A prospective screening study was carried out at the regional genetic and perinatal center in South Hungary in order to determine the efficiency of first-trimester nuchal translucency screening for fetal aneuploidies, following augmentation of the availability of nuchal translucency screening in the region by the inclusion of newly-trained hospital sonographers. Nuchal translucency thickness was measured by transvaginal sonography in 7,044 women with singleton or multiple pregnancies at weeks 10-12. Fetal karyotyping was performed when the nuchal translucency was . or = 2.5 mm, and in women with fetuses at high cytogenetic risk. Follow-up was performed in 6,841 of the 7,044 screened women. An abnormal karyotype was found in 33 cases (0.48%). The level of increased nuchal translucency was 4.5% at a cutoff of > or = 2.5 mm, and 2.8% at a cutoff of > or = 3 mm. Seventeen cases of trisomy 21, eight of trisomy 18, four of trisomy 13, one of 45,X, one of triploidy and two cases with other chromosomal abnormalities were detected. In the 33 fetuses with a chromosomal abnormality, the nuchal translucency thickness was <2.5 mm in a case of trisomy 18, > or = 2.5 mm in 32 cases and > or = 3 mm in 28 cases. With cutoffs of 2.5 mm and 3 mm, the sensitivity was 96.97% and 84.85%, respectively. Application of a nuchal translucency thickness cutoff of 2.5 mm is highly efficient for the screening of fetal aneuploidies at 10-12 weeks. This efficiency can be maintained by increasing the regional availability of nuchal translucency screening through the inclusion of newly-trained hospital sonographers.


Total evidence analysis and body size evolution of extant and extinct tortoises (Testudines: Cryptodira: Pan-Testudinidae).
Testudinidae (tortoises) is an extant clade of terrestrial turtles of worldwide distribution and with a rich fossil record that provides an exceptional context for studying their evolutionary history. Because of the lack of global phylogenetic analyses integrating extinct taxa, our current knowledge of the relationships of the total clade of Testudinidae is rather poor. To resolve this issue, we performed the first total evidence analysis of Pan-Testudinidae. The total evidence trees are congruent with the molecular topology and agree on the dichotomy of derived Testudinidae (=Testudininae; Converted Clade Name) into two previously recognized major clades, Testudona and Geochelona (New Clade Name). The integration of extinct taxa into the analysis allowed the stratigraphic fit of the total evidence trees, indicating that crown Testudininae, Testudona and Geochelona all originated by the Late Eocene, in agreement with recent molecular estimates. Ghost lineage analysis indicates high diversification in the Late Eocene and in the Miocene. The age of crown Testudo is Late Miocene, again in accordance with some molecular dates. Phylogenetic placement of fossils demonstrates that giant body size independently evolved in multiple continental mainland taxa and confirms recent results deduced from living taxa-giantism in Testudinidae is not linked to the insular effect. An unexpected outcome is the recovery of miniaturization in Testudona (<30 cm carapace length) that emerged sometime between the Oligocene and Early Miocene. No clear correlation between body size evolution and climate is apparent, but increased taxon sampling may nevertheless demonstrate the role of cooling and warming as one of many influential variables.


Beneficial effects of population bottlenecks in an RNA virus evolving at increased error rate.
RNA viruses replicate their genomes with a very high error rate and constitute highly heterogeneous mutant distributions similar to the molecular quasispecies introduced to explain the evolution of prebiotic replicators. The genetic information included in a quasispecies can only be faithfully transmitted below a critical error rate. When the error threshold is crossed, the population structure disorganizes, and it is substituted by a randomly distributed mutant spectrum. For viral quasispecies, the increase in error rate is associated with a decrease in specific infectivity that can lead to the extinction of the population. In contrast, a strong resistance to extinction has been observed in populations subjected to bottleneck events despite the increased accumulation of mutations. In the present study, we show that the mutagenic nucleoside analogue 5-azacytidine (AZC) is a potent mutagen for bacteriophage Qbeta. We have evaluated the effect of the increase in the replication error rate in populations of the bacteriophage Qbeta evolving either in liquid medium or during development of clonal populations in semisolid agar. Populations evolving in liquid medium in the presence of AZC were extinguished, while during plaque development in the presence of AZC, the virus experienced a significant increase in the replicative ability. Individual viruses isolated from preextinction populations could withstand high error rates during a number of plaque-to-plaque transfers. The response to mutagenesis is interpreted in the light of features of plaque development versus infections by free-moving virus particles and the distance to a mutation-selection equilibrium. The results suggest that clonal bacteriophage populations away from equilibrium derive replicative benefits from increased mutation rates. This is relevant to the application of lethal mutagenesis in vivo, in the case of viruses that encounter changing environments and are transmitted from cell to cell under conditions of limited diffusion that mimic the events taking place during plaque development.


How should greenhouse gas emissions be taken into account in the decision making of municipal solid waste management procurements? A case study of the South Karelia region, Finland.
The ongoing trend in the public sector is to make more sustainable procurements by taking into account the impacts throughout the entire life cycle of the procurement. Despite the trend, the only deciding factor can still be the total costs. This article answers the question of how greenhouse gas (GHG) emissions should be taken into account in municipal solid waste (MSW) management when selecting an incineration plant for source separated mixed MSW. The aim is to guide the decision making of MSW management towards more environmentally friendly procurements. The study was carried out by calculating the global warming potentials (GWPs) and costs of mixed MSW management by using the waste composition from a case area in Finland. Scenarios of landfilling and combustion in three actual waste incineration plants were used to recognise the main processes that affect the results. GWP results show that the combustion of mixed MSW is a better alternative than landfilling the waste. The GHG results from combustion are greatly affected by emissions from the combustion and substituted energy production. The significance of collection and transportation is higher from the costs' perspective than from the point of view of GHG emissions. The main costs, in addition to collection and transportation costs, result from the energy utilization or landfilling of mixed MSW. When tenders are invited for the incineration location of mixed MSW, the main focus should be: What are the annual electricity and heat recovery efficiencies and which are the substituted fuels in the area? In addition, in the case of a fluidized bed combustor it is crucial to know the combusted share of mixed MSW after preparing solid recovered fuel (SRF) and the treatment of rejects. The environmental criteria for the waste incineration plant procurements should be made in order to obtain clear instructions for the procurement units. The results can also be utilized more widely. The substituted fuels in the area and the effect of the plant location on the utilization of the produced energy can already be identified when planning an appropriate site for the waste incineration plant.


Dynamics of TIGIT and PD-1 expression on NK cells during the course of normal pregnancy.
Immune checkpoint molecules are receptors that can transmit inhibitory signals into cells to negatively modulate the immune response. However, their roles in NK cells during normal pregnancy remain poorly understood. Peripheral blood samples were collected from women during the first, second and third trimesters of pregnancy. Peripheral blood NK (pNK) cells and T cells were analyzed for the expression of the immune checkpoint molecules TIGIT and PD-1 by flow cytometry. In addition, the ability of pNK cells to secret functional molecules was also evaluated. The expression of TIGIT on pNK cells increased gradually throughout pregnancy, whereas that of PD-1 showed the opposite pattern. However, on T cells, the expression of both TIGIT and PD-1 peaked during early pregnancy, and then declined gradually thereafter. Moreover, the expressions of granzyme B, IFN-γ and CD107a by pNK cells also decreased over the course of pregnancy. Compared with TIGIT- NK cells, TIGIT + NK cells possessed reduced expression of functional molecules. As pregnancy progressed, the levels of immune checkpoint molecules expressed on pNK cells and T cells changed and the two molecules showed different trends. Furthermore, the secretion of functional molecules from pNK cells was negatively correlated with the trend of TIGIT expression, indicating TIGIT may play an important role in modulating the functions of pNK cells during pregnancy. Further study of TIGIT expression on pNK cells may enhance our understanding of its role in maintaining maternal-fetal tolerance and provide a useful marker for predicting instability during pregnancy.


Durability of glucose-lowering effect of dulaglutide in patients with type 2 diabetes mellitus: A real-world data study.
Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease requiring lifelong treatment, and durable medication is essential for maintaining stable glycemic control. This study aimed to evaluate the long-term efficacy of dulaglutide in participants who have continued the drug for more than one year. We conducted a retrospective study on 605 participants, who used dulaglutide for over one year between 2016 and 2020. Changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose, and bodyweight from baseline to last prescription day were assessed. Adherence was evaluated by the proportion of days covered (PDC), and a PDC value ≥ 0.80 was considered adherent. The mean age was 54.0 ± 11.1 years, and 46.1% were female. The mean baseline HbA1c, bodyweight, and duration of diabetes were 8.8% (72.7 mmol/mol), 75.6 kg, and 12.2 years, respectively. During the mean follow-up of 33.1 months, HbA1c and bodyweight decreased by 1.28% (14 mmol/mol, P < 0.001) and by 3.19 kg (P < 0.001), respectively. The participants were highly adherent with PDC ≥ 0.80 in 92.4% of the participants. In T2DM patients, long-term dulaglutide treatment was effective in maintaining HbA1c and weight reduction. Dulaglutide could be a favorable option of long-term treatment in real-world clinical practice.


Intuitively detecting what is hidden within a visual mask: familiar-novel discrimination and threat detection for unidentified stimuli.
Recognition without identification is the finding that, among recognition test items that go unidentified (as when a word is unidentified from a fragment), participants can discriminate those that were studied from those that were unstudied. In the present study, we extended this phenomenon to the more life-like situation of discriminating known from novel stimuli. Pictures of famous and nonfamous faces (Exp. 1), famous and nonfamous scenes (Exp. 2), and threatening and nonthreatening images (Exp. 3) were filtered in order to impede identification. As in list-learning recognition-without-identification paradigms, participants attempted to identify each image (e.g., whose face it was, what scene it was, or what was in the picture) and rated how familiar the image seemed on a scale of 0 (very unfamiliar) to 10 (very familiar). Among the unidentified stimuli, higher familiarity ratings were given to famous than to nonfamous faces (Exp. 1) and scenes (Exp. 2), and to threatening than to nonthreatening living/animate (but not to nonliving/nonanimate) images (Exp. 3). These findings suggest that even when a stimulus is too occluded to allow for conscious identification, enough information can be processed to allow a sense of familiarity or novelty with it, which appears also to be related to the sense of whether or not a living creature is a threat. That the sense of familiarity for unidentified stimuli may be related to threat detection for living or animate things suggests that it may be an adaptive aspect of human memory.


A comparative sonochemical reaction that is independent of the intensity of ultrasound and the geometry of the exposure apparatus.
Sonolysis of aqueous solutions of n-alkyl anionic surfactants results in the formation of secondary carbon-centered radicals (-*CH-). The yield of -*CH- depends on the bulk surfactant concentration up to a maximum attainable radical yield (the 'plateau yield') where an increasing surfactant concentration (below the critical micelle concentration) no longer affects the -*CH- yield. In an earlier study it was found that the ratio of -*CH- detected following sonolysis of aqueous solutions of sodium pentane sulfonate (SPSo) to that of sodium dodecyl sulfate (SDS) (i.e. CH(SPSo)/CH(SDS)) depended on the frequency of sonolysis, but was independent of the ultrasound intensity, at the plateau concentrations [J.Z. Sostaric, P. Riesz, Adsorption of surfactants at the gas/solution interface of cavitation bubbles: an ultrasound intensity-independent frequency effect in sonochemistry, J. Phys. Chem. B 106 (2002) 12537-12548]. In the current study, it was found that the CH(SPSo)/CH(SDS) ratio depended only on the ultrasound frequency and did not depend on the geometry of the ultrasound exposure apparatus considered.


[Kallmann-de Morsier syndrome: about 3 cases].
Kallmann-de Morsier syndrome (KS) is a genetic disease of the olfactory system characterized by the association of hypogonadotropic hypogonadism also referred to as gonadotropin-releasing hormone (GnRH) deficiency and anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs). Apart from sporadic cases that occur most often, familial Kallmann's syndrome is being described with increasing frequency. Diagnosis is mainly made in adolescents with absence of spontaneous puberty associated with smell disorders with hypoplasia or even aplasia of the bulbs and/or of the olfactory lobes on MRI. Sometimes, the diagnosis may be suspected in early childhood due to the association of cryptorchidism and micropénis. A mutation in one of known genes is only found in less than 30% of cases and, therefore, many other genes are still to be found. Hormone therapy allows pubertal growth in all cases and fertility can be obtained in most of the cases. We here report 3 cases of patients with this syndrome.


Preparation and Characterization of Biomass Tannin-Based Flexible Foam Insoles for Athletes.
The exploitation of bio-based foams implies an increase in the use of renewable biological resources to reduce the rapid consumption of petroleum-derived resources. Both tannins and furfuryl alcohol are derived from forestry resources and are, therefore, considered attractive precursors for the preparation of tannin-furanic foams. In addition, toughening modification of tannin-furanic foams using polyvinyl alcohol (PVOH) results in a more flexible network-like structure, which imparts excellent flexibility to the foams, whose relative properties are even close to those of polyurethane foams, which are the most used for fabrication of insoles for athletes. In addition, the addition of PVOH does not affect the thermal insulation properties of the foams by testing the thermal conductivity, resilience, and elongation at break, while reducing the brittleness of the samples and improving the mechanical properties. Also, the observation of the morphology of the foam shows that the compatibility between PVOH and tannin-furanic resin is good, and the cured foam does not show fragmentation and collapse, while the bubble pore structure is uniform. The developed flexible foam derived from biomass resources endows the foam with good thermal insulation properties and high mechanical properties, and the samples exhibit suitable physical parameters to be used as flexible insoles for athletes.


3-D image analysis of intra-cerebral brain hemorrhage from digitized CT films.
A new 3-D technique for the segmentation and quantification of human spontaneous intra-cerebral brain hemorrhage (ICH) is presented in this paper. The algorithm for ICH primary region segmentation uses the spatially weighted K-means histogram-based clustering algorithm. The ICH edema region segmentation algorithm employs an iterative morphological processing of the ICH brain data. A volume rendering technique is used for the effective 3-D visualization of ICH segmented regions. A computer program is developed for use in the human spontaneous ICH study involving a large number of patients. Experimental measurements and visualization results are presented which were computed on real ICH patient brain data.


Preoperative MRI in Patients With Intermittent Neurogenic Claudication: Relevance for Diagnosis and Prognosis.
We studied baseline magnetic resonance images of 155 patients with intermittent neurogenic claudication and lumbar spinal stenosis (LSS). Magnetic resonance imaging (MRI) and patient data were gathered from participants of a randomized trial. It is believed that the narrowness of the lumbar spinal canal correlates to the severity of complaints and that it may be a good predictor of clinical outcome if treated. However, this hypothesis has never been (prospectively) tested. MRI is an important tool to confirm the diagnosis of LSS as a cause for intermittent neurogenic claudication. Three raters were asked to evaluate the magnetic resonance images (Schizas scale). Symptom severities at baseline and 1-year follow-up were quantified. The radiological scores were correlated with clinical baseline and outcome scores to assess diagnostic and prognostic value of MRI findings at baseline. There was good agreement on the clinically relevant level of LSS (kappa range 0.57-0.64). MRI assessment of grading of compression (kappa 0.33-0.46) did not correlate with baseline MRDQ nor with outcome based on postoperative change in MRDQ (P = 0.61). However, both absence of epidural fat and presence of tortuous caudal nerves on magnetic resonance images (kappa 0.53-0.72 and 0.67-0.70) in patients with LSS were relatively good predictors for satisfactory recovery after surgery (P = 0.03 and P < 0.01). The grading of compression on the preoperative MRI is neither ambiguous nor correlating to severity of clinical condition. It does, furthermore, not have the ability to predict the outcome after 1 year if surgically treated. 2.


Aspiration and Sclerotherapy: A Minimally Invasive Treatment for Hydroceles and Spermatoceles.
To describe our contemporary experience with aspiration and sclerotherapy (AS) as a non-surgical alternative for patients with symptomatic hydrocele and spermatocele who prefer non-surgical treatment. Patients were identified by billing diagnosis code for hydrocele or spermatocele from 2015 to 2019. Patients underwent AS with doxycycline (200-400 mg). Physical examination, ultrasound and aspirate microscopy were used to differentiate hydrocele from spermatocele. Baseline and follow-up data were recorded. In total, 65 patients underwent AS, 54/65 (83%) for hydrocele and 11/65 (17%) for spermatocele with mean aspirate volumes 307 mL (SD 238 mL) and 138 mL (SD 112 mL), respectively. Follow-up data was available for 38/54 (70%) hydroceles and 8/11 (73%) spermatoceles with median follow-up 28 (IQR 23-41) and 22 (IQR 18.5-30.5) months respectively. Relief of patient reported bother associated with scrotal size occurred in 29/38 (77%) hydroceles and 8/9 (89%) spermatoceles. 2/54 (4%) hydrocele patients developed hematoma managed with in-office aspiration. Immediate post-procedural pain occurred in 2/56 (4%) hydroceles and 2/10 (20%) spermatocele. Post-procedural pain requiring more than 5 tablets of hydrocodone/acetaminophen 5mg/325mg occurred in 2/57 (3%) hydroceles and 2/10 (20%) spermatoceles. Surgical repair was ultimately pursued in 3/38 (8%) and 1/9 (11%) patients with persistent hydrocele and spermatocele respectively. AS is a safe and effective treatment alternative for hydrocele and spermatocele for patients wishing to avoid surgery.


Diet-induced obesity in mice can be treated without energy restriction using exercise and/or a low fat diet.
Diet-induced obesity was treated with a high carbohydrate, low fat diet and/or increased voluntary exercise in mice. All mice had free access to food and water during the two stage experiment. In Stage 1, 20 female mice were fed a high carbohydrate diet and 50 were made obese by consumption of a diet providing 40.8% of energy from fat. At the end of Stage 1, obese mice had significantly greater body fat stores (22.9 +/- 0.9 g/100 g body wt) than mice fed the high carbohydrate diet (12.9 +/- 1.2) (P < 0.001), yet there was no significant difference in lean body mass. In Stage 2, half of the mice were given activity wheels to increase their voluntary activity and half of the obese mice were switched to a high carbohydrate diet resulting in six groups with treatment designations of obese or lean; exercise or nonexercise, and carbohydrate or fat diets. Body fat was significantly reduced by consumption of the high carbohydrate diet (P < 0.005) and by exercise (P < 0.001), but neither treatment affected lean body mass. Exercising mice consumed significantly more energy than nonexercising mice, yet experienced a decrease in body fat and energy stores.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical factors affecting the outcome of arthrocentesis and hydraulic distension of the temporomandibular joint.
Significant psychosocial distress and substantial cost are associated with the diagnosis and management of chronic temporomandibular joint (TMJ) pain conditions. Successful intervention based on identified risk factors has potential functional and financial benefits. Arthrocentesis and hydraulic distension of the TMJ has been described as an effective modality in the treatment of patients demonstrating clinical findings consistent with the diagnosis of disc displacement without reduction. The purpose of this study was to investigate whether clinical variables such as age, gender, time since pain onset (TSO), visual analog scale (VAS) pain level, and mandibular range of motion (ROM) may predict treatment outcomes of arthrocentesis and hydraulic distension of the TMJ. The study comprised 64 consecutive patients presenting with TMJ pain, who were diagnosed with a unilateral clinical TMJ disorder of "TMJ pain associated with an internal derangement (ID) type III (disc displacement without reduction)." TMJ pain level of function and mandibular range of motion were assessed initially and then compared with the respective 2-month follow-up findings after arthrocentesis and hydraulic distension. Outcome criteria of success included an absence of signs and symptoms characteristic of a diagnosis of ID type III. A multiple logistic regression analysis of pretreatment data was used to compute the odds ratio for variables of age, gender, TSO, VAS pain level, and ROM for successful outcomes (n = 34) vs nonsuccessful (n = 30) outcomes. At 2-months follow-up, clinical evaluation showed a significant reduction in TMJ pain during function (P < .001), a significant reduction in clinical diagnoses of TMJ disorders (P < .001), and a significant increase in mandibular range of motion (P < .001). For the outcome criteria of "absence of ID type III," there was a significant difference between the clinical outcome groups for the variables of age (P = .029) and VAS pain level (P < .001). Significant increase in benefit of a successful outcome occurred with an age of < or = 25 years (11.8 odds ratio; P = .044), a VAS pain level of > 75 mm (6.5 odds ratio; P = .026), and an ROM of < 25 mm (6.9 odds ratio; P = .029). Clinical variables predicted TMJ "ID type III and pain" patients who went on to show successful treatment outcomes of arthrocentesis and hydraulic distension. Predictive modeling may provide clinicians with the opportunity to identify "at-benefit" patients early and initiate specific treatments.


It seems like cholangiocarcinoma but it is not: discovering the choledochal cyst.
A 52-year-old female was referred for a study of a left intrahepatic bile duct dilation with an initial suspicion of Klatskin. Analytically, there was no cholestasis and tumor markers were negative. On echoendoscopy, there was dilation of the intrahepatic bile duct to the confluence at the level of the left hepatic lobe, with no evidence of a lesion that could be biopsied by fine needle aspiration (FNA).


Identification of residues of functional importance within the central turn motifs present in the cytoplasmic tails of integrin alphaIIb and alphaV subunits.
Previous studies demonstrated that cell-permeable alphaIIb cytoplasmic peptides can modulate the activation of alphaIIbbeta3. An integrin activation motif was mapped to its membrane proximal region and a double proline mutant peptide and receptor indicated that its central turn motif had inhibitory capacity. However, the residues critical for inhibition of alphaIIbbeta3 activation were not identified. Using central turn peptides derived from alphaIIb and alphaV, residues critical for suppression of integrin activation were identified and the importance of these residues in protein-protein interactions was assessed. Cell-permeable peptides were used to determine the capacity of the central turn peptides to suppress alphaIIbbeta3 and alphaVbeta3 activation. Far Western analysis was used to characterize the capacity of the peptides to interact with CIB1 and surface plasmon resonance was used to characterize the binding of an antibody to the cytoplasmic tails of alphaIIb and alphaV. The central turn peptide from alphaV, alphaV(993-1001), has full inhibitory capacity while that derived from alphaIIb requires additional residues located adjacent to alphaIIb(995-1003). Within these two sequences there is a switch in the position of an asparaginine and leucine residue for a valine and glutamine (alphaIIb, RNRPPLEED; alphaV, RVRPPQEEQ). This switch had a dramatic effect on their inhibitory capacity and on protein-protein interactions. The two arginine and glutamic residues, juxtapositioned at identical locations in both subunits, appeared to be important in specifying the orientation by which proteins can dock to this region in alphaIIb and alphaV.


Community-based differentiated service delivery models incorporating multi-month dispensing of antiretroviral treatment for newly stable people living with HIV receiving single annual clinical visits: a pooled analysis of two cluster-randomized trials in southern Africa.
Differentiated service delivery (DSD) models for HIV treatment decrease health facility visit frequency and limit healthcare facility-based exposure to severe acute respiratory syndrome coronavirus 2. However, two important evidence gaps include understanding DSD effectiveness amongst clients commencing DSD within 12 months of antiretroviral treatment (ART) initiation and amongst clients receiving only single annual clinical consultations. To investigate these, we pooled data from two cluster-randomized trials investigating community-based DSD in Zimbabwe and Lesotho. Individual-level participant data of newly stable adults enrolled between 6 and 12 months after ART initiation were pooled. Both trials (conducted between August 2017 and July 2019) had three arms: Standard-of-care three-monthly ART provision at healthcare facilities (SoC, control); ART provided three-monthly in community ART groups (CAGs) (3MC) and ART provided six-monthly in either CAGs or at community-distribution points (6MC). Clinical visits were three-monthly in SoC and annually in intervention arms. The primary outcome was retention in care and secondary outcomes were viral suppression (VS) and number of unscheduled facility visits 12 months after enrolment. Individual-level regression analyses were conducted by intention-to-treat specifying for clustering and adjusted for country. A total of 599 participants were included; 212 (35.4%), 128 (21.4%) and 259 (43.2%) in SoC, 3MC and 6MC, respectively. Few participants aged <25 years were included (n = 32). After 12 months, 198 (93.4%), 123 (96.1%) and 248 (95.8%) were retained in SoC, 3MC and 6MC, respectively. Retention in 3MC was superior versus SoC, adjusted risk difference (aRD) = 4.6% (95% CI: 0.7%-8.5%). Retention in 6MC was non-inferior versus SoC, aRD = 1.7% (95% CI: -2.5%-5.9%) (prespecified non-inferiority aRD margin -3.25%). VS was similar between arms, 99.3, 98.6 and 98.1% in SoC, 3MC and 6MC, respectively. Adjusted risk ratio's for VS were 0.98 (95% CI: 0.92-1.03) for 3MC versus SoC, and 0.98 (CI: 0.95-1.00) for 6MC versus SoC. Unscheduled clinic visits were not increased in intervention arms: incidence rate ratio = 0.53 (CI: 0.16-1.80) for 3MC versus SoC; and 0.82 (CI: 0.25-2.79) for 6MC versus SoC. Community-based DSD incorporating three- and six-monthly ART refills and single annual clinical visits were at least non-inferior to standard facility-based care amongst newly stable ART clients aged ≥25 years. ClinicalTrials.gov: NCT03238846 & NCT03438370.


ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis.
The aim of this study is to provide an expression profile of ErbB/HER ligands in breast cancer. We analysed the relationships with their receptors, the bio-pathological features and prognosis. Epidermal growth factor (EGF), transforming growth factor-alpha (TGFalpha), amphiregulin (AREG), betacellulin (BTC), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EREG) and neuregulins1-4 (NRG1-4) were quantified in 363 tumours by real-time reverse transcription-polymerase chain reaction using TaqMan probes. Ligands were detected in 80%-96% of the cases, except NRG3 (42%) and EREG (45.5%). At least one ligand was expressed in 304 cases (cut-off: upper quartile). Almost all combinations of receptor and ligand co-expressions were observed, but TGFalpha is preferentially expressed in tumours co-expressing EGFR/HER3, NRG3 in those co-expressing EGFR/HER4, AREG and EREG in those co-expressing HER2/HER4. EGF and AREG were associated with estradiol receptors, small tumour size, low histoprognostic grading, high HER4 levels. TGFalpha, HB-EGF and NRG2 were negatively related to these parameters. In Cox univariate analyses, EGF was a prognostic factor. Our study demonstrates that (i) ErbB/HER ligands, including BTC and EREG, are expressed in most breast cancers; and (ii) TGFalpha, HB-EGF and NRG2 high expressions are related to the biological aggressiveness of the tumours.


Purification and properties of an aminopeptidase from rat-liver cytosol.
An aminopeptidase was purified from the rat-liver cytosolic fraction to apparent electrophoretic homogeneity. The enzyme is a monomeric protein of 95 kDa, having an isoelectric point of 4.9. Amino acid analyses indicate that the enzyme is rich in acidic amino acids and is poor in cysteine. The enzyme hydrolyzed a broad spectrum of amino acid beta-naphthylamides at a neutral pH. The enzyme also hydrolyzed di-, tri-, and oligopeptides, including physiologically active peptides such as enkephalins and Met-Lys-bradykinin. The enzyme was inhibited by metal-chelating agents, sulfhydryl-reactive reagents, N-P-tosyl-L-phenylalaninechloromethyl ketone, N-P-tosyl-L-lysinechloromethyl ketone, and puromycin but not by protease inhibitors of microbial origin. The enzyme was activated by the addition of Co2+ and sulfhydryl compounds. The aminopeptidase enhanced proteolysis when the enzyme was added to the protease assay system with purified rat-liver cytosolic neutral protease, suggesting the cooperative action of aminopeptidase in the overall process of protein degradation.


Heterosexual experience, marital status, and orientation of homosexual males.
The penile volume responses of homosexual males to pictures of nude women and men were measured and related to the subjects' marital status and experience of heterosexual intercourse. Single subjects with no experience of heterosexual intercourse and married subjects with a history of intercourse with only their wives showed significantly greater response to pictures of men compared to pictures of women than did single subjects with experience of heterosexual intercourse and married subjects with experience of intercourse with women additional to their wives. It was concluded that extensive experience of heterosexual intercourse with one partner did not reduce homosexual responsiveness as measured by subjects' penile response to pictures of nude men and women. It was further concluded that some homosexual males showed physiological evidence of a degree of bisexuality in addition to the behavioral evidence that they sought heterosexual physical relationships.


Physiologic Reduction of Hepatic Venous Blood Flow by the Valsalva Maneuver Decreases Liver Stiffness.
Liver stiffness increases after intake of food or water, suggesting that hepatic venous blood flow affects the results of elastographic measurements. This study investigated the correlation between in vivo liver stiffness and hepatic blood flow using the Valsalva maneuver for reducing intrahepatic venous blood flow. Intrahepatic changes in venous blood flow were assessed by sonography based on the pulsed wave Doppler velocity, vessel diameter assessment, and blood flow volume measurements in the portal vein and right hepatic vein. Time-harmonic elastography at 7 harmonic driving frequencies (30-60 Hz) was used to measure liver stiffness in the right liver lobe of 15 healthy volunteers. The right hepatic vein diameter, flow volume, and peak pulsed wave velocity decreased during the Valsalva maneuver from mean ± SD values of 8.64 ± 1.85 to 6.55 ± 1.84 mm (P = .002), 0.53 ± 0.23 to 0.37 ± 0.26 L/min (P = .037), and 22.14 ± 4.87 to 17.38 ± 5.41 cm/s (P = .01), respectively. This maneuver decreased liver stiffness in all volunteers by a mean of approximately 13% from 1.71 ± 0.22 to 1.48 ± 0.22 m/s (P = .00006). Our results demonstrate that liver stiffness is sensitive to altered venous blood flow, which is of clinical importance when using elastography for evaluation of portal hypertension. Furthermore, our results indicate that accurate measurement of liver stiffness requires standardized breathing conditions to rule out effects of changes in hepatic blood flow on elastographic findings.


Consequences of damage to the sensorimotor cortex in neonatal and adult cats. II. Maintenance of exuberant projections.
After chronic sensorimotor cortex ablations, sparing and greater recovery of function were seen in neonatally operated cats compared with adult operated cats. These results suggested that undamaged cortex in neonatal operates might display projections different from those of adult operates. Injections of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) were made in ipsilateral parietal cortex adjacent to the sensorimotor cortex ablations or in the contralateral sensorimotor cortex. No changes in the projections of the parietal cortex were seen in operated cats or in the projections of the undamaged sensorimotor cortical projections of adult operates. In contrast, the intact sensorimotor cortex of neonatal operates exhibited crossed corticothalamic and corticorubral projections not present in normal or adult operated animals, whereas the corticospinal tract (CST) was unchanged by the ablations. Analysis of neurons within the ventroanterior-ventrolateral nuclear complex of the thalamus ipsilateral to the ablation showed that the surviving cells of neonatal operates were equal in number but were, on average, larger than those of normals and adult operates. Some neurons in neonatal operates were larger than any seen in adult operates and normals. Injections of HRP/WGA were also made into the sensorimotor cortex of normal newborn animals. Dense bilateral corticothalamic and corticorubral projections were present. The CST had extended to lumbar levels by the day of birth but projections to the grey matter were sparse. Thus, bilateral projections seen in neonatal operates probably represent retention of some exuberant projections present in normal neonatal animals. The CST which exhibited no exuberant projection was unchanged by the lesion. The crossed corticothalamic and corticorubral projections are likely to play a role in sparing and recovery of function particularly in sparing of contact placing.


Repressor Element-1 Binding Transcription Factor (REST) as a Possible Epigenetic Regulator of Neurodegeneration and MicroRNA-Based Therapeutic Strategies.
Neurodegenerative disorders (NDD) have grabbed significant scientific consideration due to their fast increase in prevalence worldwide. The specific pathophysiology of the disease and the amazing changes in the brain that take place as it advances are still the top issues of contemporary research. Transcription factors play a decisive role in integrating various signal transduction pathways to ensure homeostasis. Disruptions in the regulation of transcription can result in various pathologies, including NDD. Numerous microRNAs and epigenetic transcription factors have emerged as candidates for determining the precise etiology of NDD. Consequently, understanding by what means transcription factors are regulated and how the deregulation of transcription factors contributes to neurological dysfunction is important to the therapeutic targeting of pathways that they modulate. RE1-silencing transcription factor (REST) also named neuron-restrictive silencer factor (NRSF) has been studied in the pathophysiology of NDD. REST was realized to be a part of a neuroprotective element with the ability to be tuned and influenced by numerous microRNAs, such as microRNAs 124, 132, and 9 implicated in NDD. This article looks at the role of REST and the influence of various microRNAs in controlling REST function in the progression of Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) disease. Furthermore, to therapeutically exploit the possibility of targeting various microRNAs, we bring forth an overview of drug-delivery systems to modulate the microRNAs regulating REST in NDD.


Evaluation of culture conditions for mixed biofilm formation with clinically isolated non-albicans Candida species and Staphylococcus epidermidis on silicone.
Silicone is frequently used in clinical and medical fields for medical devices. Mixed biofilms composed of Candida and bacterial species causes frequently failure of medical silicone devices, In this in vitro study, we analyzed mixed biofilm formation of clinically isolated non-albicans Candida species and Staphylococcus epidermidis, including Candida tropicalis, Candida krusei and Candida parapsilosis under the influence of different growth media (RPMI 1640, BHI and TSB) and several culture variables (incubation period, feeding conditions and FBS). Our results showed that culture conditions strongly influence mixed biofilm formation. TSB and BHI resulted in larger amount of biofilm formations with stronger metabolic activity of biofilms. Growth conditions may also influence the biofilm formation, which was enhanced by longer incubation period, using a fed-batch system and FBS. Therefore, the potential influences of external environmental factors are very important for mixed biofilm formation with clinically isolated non-albicans Candida species and S. epidermidis, which should be considered when designing or studying the mixed biofilm under in vitro conditions.


Assessment of knowledge, attitude, and practice about biomedical waste management among healthcare workers during COVID-19 pandemic in a health district of West Bengal.
Efforts to combat Coronavirus disease (COVID-19) pandemic have significantly increased the quantity of bio-medical waste (BMW) generation. A cross-sectional study was performed to assess the knowledge, practice, and attitude and factors affecting knowledge on BMW management among Health Care Workers (HCWs) when taking care of patients with COVID-19. This cross-sectional study was conducted among 384 HCWs, actively involved in caring of COVID-19 patients in Healthcare settings of North 24 Parganas Health District, West Bengal. Data were collected using a structured self-administered questionnaire (through Google Forms) and an observational checklist after selection criteria and having consent. The Questionnaire included four sections like the sociodemographic information, knowledge related to BMW management, observational questionnaire assessing the practice of HCWs on BMW management and rating scale related to attitudes towards BMW management. 166 HCWs (43.2%) had an excellent knowledge with overall mean score 13.5 ± 3.6. A high mean score (14.4 ± 3.2) was obtained by doctors followed by nurses (13.6 ± 3.8). Regarding practice, the majority of HCWs (52.8%) followed the color-coding of BMW and 49.5% followed policies in separating the wastes according to hazard. Doctors (91%) and nurses (81%) had more favorable attitude than others. There was a statistically significant association found among knowledge level and educational qualification (P = 0.0001), gender (P = 0.001), and work experience (P = 0.05) and work area (P = 0.05). Emphasis should be given to aware and train all HCWs regarding proper BMW management during this pandemic to prevent infection transmission.


Ochratoxin-A production in Brazilian dry beans (Phaseolus vulgaris L.).
Ochratoxin A was produced, at concentrations of about 200 mg kg1 of dry beans (Phaseolus vulgaris L.) of each of five Brazilian commercial varieties. Both intact and decorticated kernels of the varieties Preto, Branco, Rosinha, Roxo and Carioca (22% moisture) were inoculated withAspergillus alutaceous and incubated at 25°C for 28 days. Results from thin-layer and column chromatography, mass, infrared, 1H-nuclear magnetic resonance and UV-spectrometry showed that 1) the common bean is a highly stimulatory substrate for the bioproduction of ochratoxin A and 2) the putative toxin extracted by the method of Soares & Rodriguez-Amaya was in fact ochratoxin A. Removal of the seed coat resulted in increased OTA production for all varieties, particularly for the Rosinha, Roxo and Carioca.


Role of Heredity in Melanoma Susceptibility: A Primer for the Practicing Surgeon.
Melanoma is a deadly skin cancer linked to ultraviolet radiation exposure. Heritable traits and sporadic mutations modify an individual's risk for melanoma that may be associated with phenotype. Familial/heritable melanomas are broadly used to describe families with an increased incidence of melanomas, although the underlying mutation may be unknown. Mutations associated with melanoma occur in cell cycle regulation, tumor suppression, chromosomal stability, DNA repair, pigmentation, and melanocyte differentiation genes. Genetic testing of individuals with a family history of melanoma may provide additional etiologic information and ensure patients with known markers for cancer development are closely monitored by physicians.


Conformational selection of glycomimetics at enzyme catalytic sites: experimental demonstration of the binding of distinct high-energy distorted conformations of C-, S-, and O-glycosides by E. Coli beta-galactosidases.
We show that the conformational features of the molecular complexes of E. coli beta-galactosidase and O-glycosides may differ from those formed with closely related compounds in their chemical nature, such as C- and S-glycosyl analogues. In the particular case presented here, NMR and ab initio quantum mechanical results show that the 3D-shapes of the ligand/inhibitor within the enzyme binding site depend on the chemical nature of the compounds. In fact, they depend on the relative size of the stereoelectronic barriers for chair deformation or for rotation around Phi glycosidic linkage.


Mo-based catalysts for CH4/H2S reforming to hydrogen production: effect of hydroxyl concentration of the support.
High concentration of H2S in acidic natural gas will lead to poisoning of catalysts for hydrogen production by methane steam reforming, thus limiting the further use of natural gas. Reforming CH4 by H2S can be considered as an alternative route to hydrogen production from methane. This process not only achieves the removal of H2S but also obtains chemical raw material CS2 and clean energy H2. By impregnating the Mo source on SiO2 treated with hydrogen peroxide and then using the catalyst in the CH4/H2S reforming reaction, we surprisingly found that the conversion rate of CH4 and H2S increased from 28 and 32% to 34% and 43%, respectively, after hydrogen peroxide treatment. The H2 production rate and the yield of CS2 increased from 20 mmolH2/(gMo*min) and 52% to 30 mmolH2/(gMo*min) and 65%, respectively. Combining with characterization methods such as X-ray diffraction (XRD), hydrogen temperature programmed reduction (H2-TPR), 1H-based solid-state nuclear magnetic resonance (1H MAS NMR), X-ray photoelectron spectroscopy (XPS), Raman spectra (RS), and transmission electron microscopy (TEM), we found that the hydroxyl concentration of the support increased after hydrogen peroxide treatment, which led to the strengthening of the force between the metal and the support, which was easy to form low-level and small-size MoS2, exposing more active sites, and further improving the catalytic activity. This method provides a new idea for hydrogen production by CH4/H2S reforming and the development of high-performance MoS2-based catalysts.


Interplay of hot electrons from localized and propagating plasmons.
Plasmon-induced hot-electron generation has recently received considerable interest and has been studied to develop novel applications in optoelectronics, photovoltaics and green chemistry. Such hot electrons are typically generated from either localized plasmons in metal nanoparticles or propagating plasmons in patterned metal nanostructures. Here we simultaneously generate these heterogeneous plasmon-induced hot electrons and exploit their cooperative interplay in a single metal-semiconductor device to demonstrate, as an example, wavelength-controlled polarity-switchable photoconductivity. Specifically, the dual-plasmon device produces a net photocurrent whose polarity is determined by the balance in population and directionality between the hot electrons from localized and propagating plasmons. The current responsivity and polarity-switching wavelength of the device can be varied over the entire visible spectrum by tailoring the hot-electron interplay in various ways. This phenomenon may provide flexibility to manipulate the electrical output from light-matter interaction and offer opportunities for biosensors, long-distance communications, and photoconversion applications.Plasmon-induced hot electrons have potential applications spanning photodetection and photocatalysis. Here, Hoang et al. study the interplay between hot electrons generated by localized and propagating plasmons, and demonstrate wavelength-controlled polarity-switchable photoconductivity.


Long non-coding RNA TCL6 induced by SCRT1 promotes proliferation and metastasis of non-small cell lung cancer through PDK1/AKT signaling.
Non-small cell lung cancer (NSCLC) ranks the most lethal malignancies around the world, nearly 85 % of lung cancers are NSCLC. Its high prevalence and morbidity pose a considerable burden to human health, identifying promising therapeutic targets for NSCLC is urgently needed. The essential function of long non-coding RNAs (lncRNAs) in multiple cellular progressions and pathophysiological processes are widely understood, thus we investigated the role of lncRNA T-cell leukemia/lymphoma 6 (TCL6) in NSCLC progression. LncRNA TCL6 level is increased in NSCLC samples and downregulation of lncRNA TCL6 inhibited NSCLC tumorigenesis. Moreover, Scratch Family Transcriptional Repressor 1 (SCRT1) can modulate lncRNA TCL6 expression in NSCLC cells, with lncRNA TCL6 promoting NSCLC development through Pyruvate Dehydrogenase Kinase 1 (PDK1)/AKT signaling by interacting with PDK1, thereby providing a novel framework for NSCLC research.


Corynebacterium striatum empyema and osteomyelitis in a patient with advanced rheumatoid arthritis.
Corynebacterium striatum, which is a common coloniser of human skin and mucous membranes, is increasingly being recognised as an emerging pathogen. We present a case of a 69-year-old woman with empyema and osteomyelitis caused by C. striatum. To the best of our knowledge, this is the first case where these two infections from this bacterium were identified together in the same individual.


Bergapten inhibits NLRP3 inflammasome activation and pyroptosis via promoting mitophagy.
Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin phytohormone present in many herbal medicines and fruits, exibits anti-inflammatory activity. In this study we characterized the therapeutic potential of BeG against bacterial infection and inflammation-related disorders, and elucidated the underlying mechanisms. We showed that pre-treatment with BeG (20 μM) effectively inhibited NLRP3 inflammasome activation in both lipopolysaccharides (LPS)-primed J774A.1 cells and bone marrow-derived macrophages (BMDMs), evidenced by attenuated cleaved caspase-1 and mature IL-1β release, as well as reduced ASC speck formation and subsequent gasdermin D (GSDMD)-mediated pyroptosis. Transcriptome analysis revealed that BeG regulated the expression of genes involved in mitochondrial and reactive oxygen species (ROS) metabolism in BMDMs. Moreover, BeG treatment reversed the diminished mitochondrial activity and ROS production after NLRP3 activation, and elevated the expression of LC3-II and enhanced the co-localization of LC3 with mitochondria. Treatment with 3-methyladenine (3-MA, 5 mM) reversed the inhibitory effects of BeG on IL-1β, cleaved caspase-1 and LDH release, GSDMD-N formation as well as ROS production. In mouse model of Escherichia coli-induced sepsis and mouse model of Citrobacter rodentium-induced intestinal inflammation, pre-treatment with BeG (50 mg/kg) significantly ameliorated tissue inflammation and injury. In conclusion, BeG inhibits NLRP3 inflammasome activation and pyroptosis by promoting mitophagy and maintaining mitochondrial homeostasis. These results suggest BeG as a promising drug candidate for the treatment of bacterial infection and inflammation-related disorders.


Hemorrhoidectomy in the patient with multiple or circumferential hemorrhoids.
A technique is presented that allows complete removal of hemorrhoids even when large hemorrhoids exist between the classic three major hemorrhoidal locations. Since the anorectal mucosa overlying these "interval" hemorrhoids is preserved, there is no increased tendency for stricture formation to occur.


Regulation of the human skeletal muscle chloride channel hClC-1 by protein kinase C.
1. The regulation of a recombinant human muscle chloride channel, hClC-1, by protein kinase C (PKC) was investigated in human embryonic kidney (HEK 293) cells. 2. External application of 4beta-phorbol esters (4beta-PMA) reduced the instantaneous whole-cell current amplitude over the entire voltage range tested. This effect was abolished when the cells were intracellularly perfused with a specific protein kinase C inhibitor, chelerythine. Inactive 4alpha-phorbolesters did not affect the chloride currents. We conclude that the effect of 4beta-phorbol esters is mediated by protein kinase C (PKC). 3. Activation of PKC resulted in changes in macroscopic current kinetics. The time course of current deactivation determined in the presence and absence of 4beta-phorbol esters could be fitted with the sum of two exponentials and a constant value. In the presence of phorbol esters, the fast time constants and the minimum value of the fraction of non-deactivating current were increased, whereas the voltage dependence of all fractional current amplitudes remained unchanged. PKC-induced phosphorylation had only small effects on the voltage dependence of the relative open probability and the maximum absolute open probability was unaffected by treatment with 4beta-PMA, as shown by non-stationary noise analysis. 4. The kinetic changes indicate that phosphorylation alters functional properties of active channels. Since the absolute open probability is not reduced, the observed macroscopic current reduction implies alterations of the ion permeation process. 5. Phosphorylation by PKC appears to affect ion transfer and gating processes. It is postulated that the phosphorylation site may be located at the cytoplasmic vestibule face of the pore.


Formation and Entrapment of Tris(8-hydroxyquinoline)aluminum from 8-Hydroxyquinoline in Anodic Porous Alumina.
The formation and entrapment of tris(8-hydroxyquinoline)aluminum (Alq₃) molecules on the surface of anodic porous alumina (APA) immersed in an ethanol solution of 8-hydroxyquinoline (HQ) were investigated by absorption, fluorescence, and Raman spectroscopies. The effects of the selected APA preparation conditions (galvanostatic or potentiostatic anodization method, anodizing current and voltage values, one- or two-step anodizing process, and sulfuric acid electrolyte concentration) on the adsorption and desorption of Alq₃ species were examined. Among the listed parameters, sulfuric acid concentration was the most important factor in determining the Alq₃ adsorption characteristics. The Alq₃ content measured after desorption under galvanostatic conditions was 2.5 times larger than that obtained under potentiostatic ones, regardless of the adsorbed quantities. The obtained results suggest the existence of at least two types of adsorption sites on the APA surface characterized by different magnitudes of the Alq₃ bonding strength. The related fluorescence spectra contained two peaks at wavelengths of 480 and 505 nm, which could be attributed to isolated Alq₃ species inside nanovoids and aggregated Alq₃ clusters in the pores of APA, respectively. The former species were attached to the adsorption sites with higher binding energies, whereas the latter ones were bound to the APA surface more weakly. Similar results were obtained for the Alq₃ species formed from the HQ solution, which quantitatively exceeded the number of the Alq₃ species adsorbed from the Alq₃ solution. Alq₃ molecules were formed in the HQ solution during the reaction of HQ molecules with the Al3+ ions in the oxide dissolution zone near the oxide/electrolyte interface through the cracks and the Al3+ ions adsorbed on surface of pore and cracks. In addition, it was suggested that HQ molecules could penetrate the nanovoids more easily than Alq₃ species because of their smaller sizes, which resulted in higher magnitudes of the adsorption.


Methyl group turnover on methyl-accepting chemotaxis proteins during chemotaxis by Bacillus subtilis.
The addition of attractant to Bacillus subtilis briefly exposed to radioactive methionine causes an increase of labeling of the methyl-accepting chemotaxis proteins. The addition of attractant to cells radiolabeled for longer times shows no change in the extent of methylation. Therefore, the increase in labeling for the briefly labeled cells is due to an increased turnover of methyl groups caused by attractant. All amino acids gave enhanced turnover. This turnover lasted for a prolonged time, probably spanning the period of smooth swimming caused by the attractant addition. Repellent did not affect the turnover when added alone or simultaneously with attractant. Thus, for amino acid attractants, the turnover is probably the excitatory signal, which is seen to extend long into or throughout the adaptation period, not just at the start of it.


A fatal case of accidental oral formaldehyde poisoning and its pathomorphological characteristics.
Formaldehyde is a colourless irritating gas at room temperature, which, therefore, is usually stored in liquid form. This compound is often used as an antiseptic, disinfectant and fumigant in biology and medicine. Formaldehyde, as a potential carcinogen confirmed by the World Health Organization (WHO), is seriously harmful to human systems, such as the respiratory system, immune system and reproductive system. This article reports a case of a 50-year-old woman who died after accidentally drinking 25% formaldehyde solution in a transparent plastic bottle. Anatomical examination revealed fixed tissue morphology of the stomach and adjacent organs. The toxicity test results showed that the concentrations of formaldehyde in the blood and gastric tissue were 36.56 mg/kg and 274.48 mg/kg, respectively, which was consistent with death from formaldehyde poisoning. Due to the particular smell of formaldehyde, poisoning by accidentally drinking formaldehyde solution is rare. Of late, the mechanism of death from formaldehyde poisoning is that it rapidly causes coagulation of tissue cell protein, which may lose its normal function. Based on the pathological characteristics of the case, we put forward a new viewpoint on the mechanism of death from formaldehyde poisoning in which formaldehyde causes rapid fixation of blood in the tissue, thus leading to acute circulatory disturbance.


Zinc deficiency with acrodermatitis enteropathica-like eruption after pancreaticoduodenectomy.
Pancreaticoduodenectomy (PD) is the standard operation for periampullary lesions. Most reports have focused on the clinical outcome, complications and tumor recurrence after PD. Few studies have focused on the nutritional sequelae that result from the extended resection of the upper gastrointestinal tract and disruption of the normal physiologic process of digestion. Zinc is absorbed mainly in the duodenum and proximal jejunum, which are removed during PD. Herein, we report two patients who experienced zinc deficiency with acrodermatitis enteropathica-like eruption, alopecia, glossitis and nail dystrophy after PD. The lesions improved dramatically after supplementation with zinc sulfate, pancreatic enzyme and diet instructions. No symptoms related to zinc deficiency were noted on follow-up after nutritional instructions had been given to the patients.


Characterization of mouse Eppin and a gene cluster of similar protease inhibitors on mouse chromosome 2.
We have recently described a novel gene on human chromosome 20q 12-13.2 called Eppin (Epididymal protease inhibitor) that expresses three mRNAs encoding two isoforms of a cysteine-rich protein containing both Kunitz-type and WAP-type (four disulfide core) consensus sequences (Richardson et al., 2001). To further our studies on Eppin, we have cloned, sequenced and characterized mouse Eppin and report that it lies within a 200 Kb cluster of putative Eppin-like genes on mouse chromosome 2. Analysis of the homologies between the genes in the human and mouse Eppin clusters indicates that the first part of the cluster immediately surrounding Eppin represents a conserved linkage because the order of homologous genes is conserved. Sequencing of reverse transcription polymerase chain reaction (RT-PCR) products confirmed the expression of five of these novel Eppin-like genes in the mouse, which include the mouse homologue of HE-4. These genes are characterized by having either one or both of the Kunitz-type and WAP-type consensus sequences. Additional RT-PCR experiments revealed that expression of some of the Eppin-like genes is restricted to epididymis and testis while others are expressed in several somatic tissues. Northern blot analysis of 22 different mouse tissues identified Eppin transcripts only in the epididymis and testis. Immunostaining of Eppin with anti-recombinant mouse Eppin demonstrated Eppin predominantly on the postacrosomal region of mouse spermatozoa, in Sertoli cells, Leydig cells, and round spermatids in the testis, and in the principal cells of the cauda epididymidis epithelium. Eppin is first expressed by Sertoli cells of 12-day-old mice and subsequently in round spermatids, which is consistent with androgen regulation. Our results demonstrate that mouse chromosome 2 contains a conserved linkage of Eppin-like protease inhibitor genes that are expressed in the epididymis.


[Pathologists as victims of National Socialism : Results of a quantitative cross-sectional study].
This explorative study focuses on those pathologists who became victims of the Third Reich by being dismissed, disenfranchised, persecuted, expelled, murdered, or driven to suicide. Accordingly, it examines the question of how many - and which - pathologists were oppressed in the Nazi dictatorship. It also looks at the reasons for this and the effects that repression has had on the lives of those affected - both in the Third Reich and in postwar Germany. The study is based on archival source material, which was supplemented by a systematic evaluation of the relevant research literature. In total, the biographies of 89 pathologists could be reconstructed and evaluated. Of these, 67 persons were persecuted for "racial" or anti-Semitic reasons. Until their disenfranchisement, the majority were employed at a university. The majority of the examined pathologists fled abroad, with most immigrating to the USA and Great Britain and successfully establishing themselves there professionally. No indications of a return to their homeland could be found in the sample presented here. Reasons included a lack of career options and negative personal experiences in postwar Germany, such as in reparation proceedings. Quite a lot of those who remained in the German Reich died violently, either in concentration camps or by suicide.


The mechanical property and corrosion resistance of Mg-Zn-Nd alloy fine wires in vitro and in vivo.
Titanium and its alloy are commonly used as surgical staples in the reconstruction of intestinal tract and stomach, however they cannot be absorbed in human body, which may cause a series of complications to influence further diagnosis. Magnesium and its alloy have great potential as surgical staples, because they can be degraded in human body and have good mechanical properties and biocompatibility. In this study, Mg-2Zn-0.5Nd (ZN20) alloy fine wires showed great potential as surgical staples. The ultimate tensile strength and elongation of ZN20 alloy fine wires were 248 MPa and 13%, respectively, which could be benefit for the deformation of the surgical staples from U-shape to B-shape. The bursting pressure of the wire was about 40 kPa, implying that it can supply sufficient mechanical support after anastomosis. Biochemical test and histological analysis illustrated good biocompatibility and biological safety of ZN20 alloy fine wire. The residual tensile stress formed on the outside of ZN20 fine wire during drawing would accelerate the corrosion. The second phase had a negative influence on corrosion property due to galvanic corrosion. The corrosion rate in vitro was faster than that in vivo due to the capsule formed on the surface of ZN20 alloy fine wire.


[Validation and environmental control of preparation operations. Fifth communication of the Comite des Laboratoires et Services Officiels de Controle des Medicaments et de la Section des Pharmaciens de l'Industrie'-F.I.P, May 1990].
The many different check-points concerning the complementary activities of validation and monitoring of aseptically processed pharmaceutical preparations are described. The features are based on the official and current GMP guidelines. These are outlined in practical terms according to the personal experience of the authors and manufacturing specialists who were consulted.


Business models of the French veterinary offices in rural areas and regulation of veterinary drug delivery.
French veterinarians are authorised to both prescribe and deliver drugs. This situation of conflict of interest is sometimes denounced as a potential source of over-prescription and overuse of veterinary antimicrobials, even if no evidence is available up to now. This leads to regular calls for separating prescription from drug delivery, even if the consequences of such separation are unknown. The present work aims at describing the business model of French veterinary offices and the expected impact of separation on those offices. A dataset of 15 million observations was built with structural and accounting data collected for the period 2015-2017 from French mixed veterinary offices. Results of the baseline scenario indicate that veterinary offices' profit generated from farm animal activities is mainly driven by drug delivery (about 70%), while profit from companion animal activities is mainly driven by medical acts (i.e., consultation and advice, surgery, and laboratory analysis) and sale of accessory products (about 65%). The net margin rate is higher than 25% for all activities, except for material selling. If drug delivery or sales associated with a medical act (same day, same client, and same animal) do not require additional human resources (alternative scenario), the net margin is reduced for medical acts. For both scenarios, a high variability is observed between veterinary offices. This shows that the profit of each activity is highly driven by time spent on the activities. Our results suggest that, in the case of restrictions on drug delivery by veterinarians, their profit may dramatically decrease, especially for farm animal practitioners and those with low medical acts profitability. Further work is needed to account for the high diversity of situations faced by veterinary offices and the sensitivity of their profitability to production costs.


Photocatalytic degradation of imidacloprid by optimized Bi2WO6/NH2-MIL-88B(Fe) composite under visible light.
Imidacloprid as a widely used neonicotinoid insecticide can cause harmful pesticide residue inevitably. Metal-organic frameworks (MOFs) were innovatively composited to improve the light absorption and degradation performance of Bi2WO6 semiconductor, which expanded the photodegradation application in solving environmental problems. Based on the synergistic effect of Bi2WO6 and NH2-MIL-88B(Fe), a Bi2WO6/NH2-MIL-88B(Fe) (BNM) heterojunction photocatalyst with high-performance of photocatalytic degradation activities was successfully synthesized. The optimized BNM catalyst had a good degradation rate under visible light, which was mainly caused by generation of the active ·OH. Transient photocurrent response and electrochemical impedance tests verified that 1:2 BNM exhibits a highest charge separation and a lowest carrier recombination rate which were favorable to the photocatalytic activity. Cycle experiments show that the composite photocatalyst had good reusability and stability which were very important for potential industry applications.


Monte Carlo calculated beam quality correction factors for two cylindrical ionization chambers in photon beams.
Although several studies provide data for reference dosimetry, the SNC600c and SNC125c ionization chambers (Sun Nuclear Corporation, Melbourne, FL) are in clinical use worldwide for which no beam quality correction factors kQ are available. The goal of this study was to calculate beam quality correction factors kQ for these ionization chambers according to dosimetry protocols TG-51, TRS 398 and DIN 6800-2. Monte Carlo simulations using EGSnrc have been performed to calculate the absorbed dose to water and the dose to air within the active volume of ionization chamber models. Both spectra and simulations of beam transport through linear accelerator head models were used as radiation sources for the Monte Carlo calculations. kQ values as a function of the respective beam quality specifier Q were fitted against recommended equations for photon beam dosimetry in the range of 4 MV to 25 MV. The fitting curves through the calculated values showed a root mean square deviation between 0.0010 and 0.0017. The investigated ionization chamber models (SNC600c, SNC125c) are not included in above mentioned dosimetry protocols, but are in clinical use worldwide. This study covered this knowledge gap and compared the calculated results with published kQ values for similar ionization chambers. Agreements with published data were observed in the 95% confidence interval, confirming the use of data for similar ionization chambers, when there are no kQ values available for a given ionization chamber.


[Variability in the recommendations for the clinical management of osteoporosis].
Analysis of the variability in the recommendations of the main guidelines and clinical documents for the management of osteoporosis. Searches were carried out in PubMed, Google, web pages of national and international scientific societies related to the management of osteoporosis, and agencies that develop guidelines. We analyzed guidelines and clinical documents that included recommendations for the indication of bone densitometry and/or pharmacological treatment, which could influence the management of osteoporosis in the Spanish National Health System, which have been published between 2006 and 2012. We included 12 documents. Eleven recommend performing bone densitometry upon assessing women risk factors, but the number and type of risk factors vary between documents: 6 recommend its implementation to all women over 65 years, 4 in men aged 65-70 years, and 3 when there is radiological suspicion of osteoporosis. There is agreement on the recommendations on the indication for densitometry to monitor drug response. In primary prevention, all national documents combined risk factors and densitometric osteoporosis and 3 of them recommend individual assessment according to risk factors. Most of the international guidelines require the calculation of risk with the FRAX(®) tool. In secondary prevention, all documents recommend treatment in cases of hip or clinical vertebral fracture; in men, and for the rest of fractures, the recommendations are heterogeneous. Overall there is a high variability in the recommendations of guidelines and other documents for the management of osteoporosis.


Patients need emotional support: Managing physician disclosure information to attract more patients.
Information asymmetry causes barriers for the patient's decision-making in the online health community. Patients can rely on the physician's self-disclosed information to alleviate it. However, the impact of physician's self-disclosed information on the patient's decision has rarely been discussed. To investigate the impact of the physician's self-disclosed information on the patient's decision in the online health community and to examine the moderating effect of the physician's online reputation. Drawing on the limited-capacity model of attention, we develop a theoretical model to estimate the impact of physician's self-disclosure information on patient's decision and the contingent roles of physician's online reputation in online healthcare community by econometric methods. We designed a web crawler based on R language program to collect more than 20,000 physicians' data from their homepage in Haodf-a leading online healthcare community platform in China. The attributes of the physician's information disclosure are measured by the following variables: emotion orientation, the quantity of information and the semantic topics diversity. The empirical analysis derives the following findings: (1) The emotion orientation in physician's self-disclosure information is positively associated with patient's decision; (2) Both excessive quantity of information and semantic topics diversity can raise barriers for patient's decision; (3) When the level of physician's online reputation is high, the negative effect of the quantity of information and semantic topics diversity are all strengthened while the positive effect of the emotion orientation is not strengthened. This study has a profound importance for a deep understanding of the impact of physician's self-disclosure information and contributes to the literature on information disclosure, the limited capacity model of attention, patient's decision. Also, this study provides implications for practice.


Hemolytic uremic syndrome: a case report from Africa.
Hemolytic uremic syndrome (HUS) is not a rare disease. In the tropics with high incidence of diarrhea diseases and their subsequent complications HUS can easily be missed or overlooked. We present a case of HUS highlighting its multi systemic presentation and its management in a resource poor setting where a acute dialysis and plasma exchange are limited in availability and cost.


[Scimitar syndrome. Correlation anatomo-embryological].
To describe morphologically a toracoabdominal visceral block of a scimitar's syndrome case. We propose a pathogenetic theory wich explains the development of the pulmonary venous connection in this syndrome. The anatomic specimen was described with the segmental sequential system. The situs was solitus, the connections between the cardiac segments and the associated anomalies were determined. The anatomy of both lungs, including the venous pulmonary connection, was described. A pathogenetic hypothesis was made, which explains the pulmonary venous connection throw a correlation between the pathology of this syndrome and the normal development of the pulmonary veins. The situs was solitus, the connections of the cardiac chambers were normal; there were hypoplasia and dysplasia of the right lung with sequestration of the inferior lobe; the right pulmonary veins were connected with a curved collector which drainaged into the suprahepatic segment of the inferior vena cava; the left pulmonary veins were open into the left atrium. The sequestered inferior lobe of the right lung received irrigation throw a collateral aortopulmonary vessel. There was an atrial septal defect. The pathogenetic hypothesis propose that the pulmonary venous connection in this syndrome represent the persistent of the Streeter's horizon xiv (28-30 days of development), period in which the sinus of the pulmonary veins has double connection, with the left atrium and with a primitive collector into the right viteline vein which forms the suprahepatic segment of the inferior vena cava.


Miniature equipment for the perfusion of rat limbs.
A simple, reliable and efficient miniaturized extracorporeal circulation system for the use in small animals, especially for the perfusion of rat hind limbs, has been described. The system consists of a newly devised bubble oxygenator and heat exchanger and of commercially available roller pumps, polyethylene cannulas and silicone tubes. The minimal and maximal priming volume of the entire system is 4.7 and 16.7 ml, respectively. The efficiency of the system is reflected in a high value of oxygen uptake in the range of 0.061 ml O2 X min-1 X ml-1 blood, a heat transfer coefficient ranging from 0.96 to 0.31 at flow rates between 1 and 20 ml X min-1, a low pulsation amplitude of the roller pump, a constant flow resistance at the arterial cannula, which implies optimal flow conditions, and in a low blood trauma with plasma hemoglobin concentrations of 47.5 +/- 5 mg dl-1 after 60 min of in vitro perfusion.


Harvesting Rib Cartilage in Primary and Secondary Rhinoplasty.
Satisfactory and consistent long-term results in primary and secondary rhinoplasty rely on adequately resupporting or reconstructing the nasal osseocartilagenous framework. Autogenous rib cartilage has been our graft material of choice for major nasal reconstruction when sufficient septal cartilage is not available. The rib provides the most abundant source of cartilage for graft fabrication and is the most reliable when structural support is needed.


Functional outcome following a locked fracture-dislocation of the calcaneus.
Locked fracture-dislocations of the calcaneus are uncommon, and a substantial number of these injuries is not recognised or is misdiagnosed at first presentation. The primary aim of this study was to evaluate the long-term outcome in patients with this injury. This is a retrospective cohort study of adult patients who sustained a uni- or bilateral calcaneal fracturedislocation. Outcome was measured using validated questionnaires, including the American Orthopaedic Foot and Ankle Society Hindfoot score (AOFAS), Foot Function Index (FFI) and a visual analogue scale (VAS). During the 12-year study period a total of 16 patients with 17 locked fracture-dislocations were identified. This represented 6 % of all surgically treated calcaneal fractures (17 of 279). The median follow-up was 48 months. All patients were treated using an extended lateral approach and plate fixation. In one patient with a delayed presentation a primary arthrodesis was performed. The functional outcome scores were available for 14 patients with 14 fractures. The median AOFAS was 74 [interquartile range (IQR) 47–86], the median FFI was 18 (IQR 6–37) and the median VAS for overall satisfactionwas 8.2 (IQR 5.5–9.4). A secondary fusion was deemed necessary in three cases. This study shows that, with surgical treatment via an extended lateral approach, the outcome in patients with a locked fracture-dislocation of the calcaneus is similar to the outcome of other displaced intra-articular calcaneal fracture types. However, a higher rate of secondary subtalar fusion can be expected.


Does rating with a checklist improve the effect of E-learning for cognitive and practical skills in bariatric surgery? A rater-blinded, randomized-controlled trial.
Mental training of laparoscopic procedures with E-learning has been shown to translate to the operating room. The present study aims to explore whether the use of checklists during E-learning improves transfer of skills to the simulated OR on a Virtual Reality (VR) trainer for Roux-en-Y gastric bypass (RYGB). Laparoscopy naive medical students (n = 80) were randomized in two groups. After an E-learning introduction to RYGB, checklist group rated RYGB videos using the validated Bariatric Objective Structured Assessment of Technical Skills (BOSATS) checklist while group without checklist only observed the videos. Participants then performed RYGB on a VR-trainer twice and were evaluated by a blinded expert rater using BOSATS. A multiple choice (MC) knowledge test on RYGB was performed. Suturing on a cadaveric porcine small bowel was evaluated using objective structured assessment of technical skill (OSATS). Checklist group was better in the knowledge test (A 8.3 ± 1.1 vs. B 7.1 ± 1.3; p ≤ 0.001) and there was a trend towards better VR RYGB performance (BOSATS) on the first try (85.9 ± 10.2 vs. 81.1 ± 11.5; p = 0.058), but not on the second try (92.0 ± 9.7 vs. 89.3 ± 10.5; p = 0.251). Suturing as measured by OSATS was not different (29.5 ± 3.0 vs. 29.0 ± 3.5; p = 0.472). This study presents evidence that the use of a BOSATS checklist during E-learning helps trainees to improve their knowledge acquisition with E-learning. The transfer from mental training to the simulated OR environment seems to be partially enhanced by use of the BOSATS checklist. However, more research is required to investigate potential benefits.


Standardized high-performance liquid chromatography of 182 mycotoxins and other fungal metabolites based on alkylphenone retention indices and UV-VIS spectra (diode array detection).
A general standardized method for the analysis of mycotoxins and other fungal secondary metabolites has been developed, based on high-performance liquid chromatography (HPLC) with an alkylphenone retention index and photodiode-array detection combined with thin-layer chromatography (TLC) in two different eluents. Each fungal secondary metabolite is characterized by its bracketed alkylphenone retention time index, its UV-VIS absorption maxima and its retardation factors relative to griseofulvin in two TLC eluents. This system is effective for the comparison of chemotaxonomic data in different laboratories and for a precise identification of fungi based on organic solvent extracts of fungal cultures. All important groups of mycotoxins and other fungal secondary metabolites could be detected in the HPLC system described and data are listed for 182 metabolites. The fungal secondary metabolites separated and characterized include aflatoxin B1, B2, G1 and G2, ochratoxin A, citrinin, penicillin acid, viomellein, penitrem A, patulin, sterigmatocystin, alternariol, tenuazonic acid, trichothecenes, roquefortines, fusarin C, zearalenone, PR-toxin, citreoviridin, viridicatumtoxin, verruculogen, rugulosin, cyclopiazonic acid, penicillin G and many other alkaloids, polyketides and terpenes.


Strength and fracture toughness of MgO-modified glass infiltrated alumina for CAD/CAM.
This study was conducted to investigate the effect of MgO additive to Al2O3 on the flexural strength, fracture toughness of glass infiltrated alumina for CAD/CAM application. Alumina blanks with additive of 0.5 wt% MgO were prepared via isostatic pressing and sintering at 1400 degrees C for 2h, and then alumina-glass composites were fabricated by infiltrating the molten glass into the partially sintered alumina compact. Flexural strength and fracture toughness were determined using three point bending methods and a single edge notched beam method. The mechanism of crack propagation was observed under a field emission scanning electron microscope. The three-point flexural strength and fracture toughness of partially sintered alumina and alumina-glass composite were 210 MPa, 1.86 MPam(1/2), and 432.2 MPa, 5.12 MPam(1/2), respectively, and they were free of shrinkage during the processing of glass infiltration. The field emission SEM micrograph indicated that indentation caused a non-planar crack propagation including crack deflection and crack bowing. MgO was used as an additive to alumina to improve the strength and fracture toughness of partially sintered alumina and alumina-glass composite. The high strength and toughness are related to toughening by the distribution of alumina with uniform particle sizes, crack bowing, crack deflection and the beneficial wetting properties of the particle surface.


A cluster of charged and aromatic residues in the C-terminal portion of maltoporin participates in sugar binding and uptake.
The maltoporin LamB of Escherichia coli K12 is a trimeric protein which facilitates the diffusion of maltose and maltodextrins through the bacterial outer membrane, and also acts as a non-specific porin for small hydrophilic molecules as well as a receptor for phages. Loop L9 (residues 375 to 405) is the most distal and largest surface-exposed loop of LamB. It comprises a central portion, which varies in size and sequence in the maltoporins of known sequence, flanked by two conserved regions containing charged and aromatic residues. In order to identify the residues within the proximal region that are specifically involved in sugar utilization, we used site-directed mutagenesis to change, individually, each of the charged (five) and aromatic (three) residues in the region 371 to 379 into alanine. None of the eight single amino acid substitutions affected the phage receptor activity of LamB. In contrast, they all affected, to variable extents, maltoporin functions. For all the mutants, very good correlations were observed between the effects on sugar binding and on in vivo uptake. In no case were maltoporin functions completely abolished. Mutants E374 A and W376 A were the most impaired (with over 60% reduction in dextrin binding and in vivo uptake of maltose and maltopentaose). These two mutations also led to an increased bacterial sensitivity to bacitracin and vancomycin. The functional and structural implications are discussed.


The role of apoptosis in blepharoptosis.
The purpose of this study is to evaluate the role of apoptosis in the pathogenesis of blepharoptosis. Forty-five eyelids of 43 consecutive patients (16 female, 27 males) that underwent levator resection surgery for ptosis correction were included in the study. Twenty-six of the eyelids had congenital myogenic ptosis and 19 had aponeurotic ptosis. Levator palpebrae superioris function and height of the vertical palpebral fissure were measured in all patients. After levator resection surgery, the distal part of the levator aponeurosis was fixed and sent for evaluation. Apoptotic cells were detected using Apop Tag Plus Peroxidase In Situ Apoptosis Detection Kit. The mean levator palpebrae superioris function was 8.4 mm (range 5-10 mm) in congenital ptosis group and 12.1 mm (range 10-17 mm) in the aponeurotic ptosis group. The mean height of the vertical palpebral fissure in patients with congenital ptosis and aponeurotic ptosis were 6.5 mm (range 5-9 mm) and 6.1 mm (3-9 mm), respectively. The mean apoptotic index of congenital ptosis and aponeurotic ptosis were 27.3 (16-39) and 29.8 (18-41), respectively. There was no statistically significant difference between congenital and aponeurotic ptosis groups in a mean apoptotic index (P<0.05). Apoptotic index was not correlated with age, levator palpebrae superioris function, palpebral fissure height, and lid crease height in two groups. We found no statistically significant difference between two subtypes of blepharoptosis regarding apoptosis. According to this study, apoptosis seems to have no significant role in the development of aponeurotic blepharoptosis.


Captopril treatment in rheumatic heart disease with congestive heart failure. A preliminary report.
A small scale controlled trial of captopril (ACE inhibitor) was conducted in 8 children with congestive heart failure due to rheumatic mitral regurgitation with or without mild mitral stenosis. The age of the patient ranged from 5.5 to 13 years (mean 9.3 years). Four children, served as control group, received digitalis and diuretics as standard treatment; while the other 4 children also received 2 x 12.5 mg of captopril in addition to standard treatment. The effect of both regimens were measured by using changes of left ventricular function as seen on the echocardiogram performed before treatment, and then 3, 7 and 14 days thereafter. Definite conclusion cannot be made because of the small number of patients; but it is apparent that some improvements of left ventricular functions in the captopril group were more evident when compared with that of the control group of standard treatment. Side effects of captopril were not found.


The benefits of navigated intraoperative ultrasonography during resection of fourth ventricular tumors in children.
Safe and radical excision of pediatric fourth ventricular tumors is by far the best line of management. Pediatric fourth ventricular tumor surgery is a challenge for neurosurgeons. The aim of the study is to present the authors' experience and to evaluate the possible benefits of neuro-navigated intraoperative ultrasonography (NIOUS) during the surgery of fourth ventricular tumors in children. Nonrandomized clinical trial study was conducted on 60 children with fourth ventricular tumors who were treated at Children's Cancer Hospital-Egypt. Mean age was 5.2 (±2.6) years. Thirty cases were operated upon utilizing the conventional microneurosurgical techniques. Another 30 cases were operated upon utilizing the NIOUS technique. Total tumor excision was achieved in 29 cases (96.7%) of NIOUS group versus 24 cases (80%) in the conventional group. Mean operative time NIOUS group was 150 min [standard deviation (SD) = 18.28) versus 140.6 min (SD = 18.6) in the conventional group (p value = 0.055). The mean operative blood loss was 67.5 ml (SD = 17) in NIOUS group versus 71 ml (SD = 15.4) in the conventional group. Postoperative cerebellar mutism occurred in one case (3.3%) of NIOUS group versus in six cases (20%) of the conventional group. Integration of navigated intraoperative ultrasonography in surgery of pediatric fourth ventricular tumors is a useful technology. It safely monitors maximum stepwise tumor excision. It is associated with less operative morbidity without significantly added operative time. It is a real-time, cost-effective, easily applicable, and easily interpretable tool that could substitute the use of intraoperative MRI especially in pediatric neurosurgery.


Visualization of both peroxidase and acid phosphatase isozymes from flax (Linum) on the same gels.
The staining of both peroxidases (PERs) and acid phosphatases (APs) following electrophoresis on acrylamide gels is described. Scanning doubly stained gels at appropriate wavelengths reveals individual isozyme bands for both enzyme systems, giving essentially identical results to those obtained from separately run and stained gels. Collection of relative mobility (Rm) data is unaffected by such tandem staining. Few complications arise from overlapping PER and AP bands, or interactions between the two staining methods and PER or AP isozymes. Even if repeat scans of a gel at different wavelengths are needed to retrieve all isozyme information, dual staining provides distinct savings in time and sample material.


Acute appendicitis: Factors associated with inconclusive ultrasound study and the need for additional computed tomography.
To identify variables associated with inconclusive ultrasound examination and the need for further abdominopelvic computed tomography (CT) examination for the diagnosis of acute appendicitis. A total of 105 adult patients with acute appendicitis were included. There were 55 patients (38 men, 17 women; mean age, 23±9 [SD] years; range: 15-58 years) with a diagnosis of acute appendicitis using ultrasound alone and 50 patients (30 men, 20 women; mean age, 31±14 [SD] years; range: 16-83 years) who required further CT. Demographic, clinical, and biological criteria and appendix location were compared between the two groups to search for variables associated with the need of further CT. Patients who required further CT were older (31.1±14 [SD] years) and had a greater body mass index (BMI) (26.7±4.3 [SD]kg/m2) than those who did not require CT (23±9 [SD] years and 22.9±3.4 [SD]kg/m2), respectively (P<0.01). A greater proportion of patients with complicated acute appendicitis was observed in patients who required further CT (9/50; 18%) than in those who had only ultrasound (1/55; 2%) (P=0.012). Atypical appendix location was more frequent in patients who required CT (19/50; 36%) than in those who had only ultrasound (6/55; 11%) (P<0.001). There were no significant differences regarding gender, inflammatory syndrome and hours of imaging (on call vs. working hours) between the two groups. Advanced age, high BMI, atypical appendix location, and complicated appendicitis are associated with inconclusive ultrasound and the need for further CT to diagnose acute appendicitis.


Evaluation and treatment of impotence: a pragmatic approach addressing organic and psychogenic components.
Twelve patient referrals for evaluation of impotence comprise the subjects of a pilot study examining psychogenic and biogenic factors of erectile dysfunction. A structured interview format (KCII) was developed which allowed the clinician to estimate the likelihood of the presence of three organic factors (hormonal, neurological, cardiovascular) and three psychogenic factors (intrapsychic, relational, and behavioral) as well as the presence of relevant lifestyle factors (alcohol, smoking, exercise patterns). The results demonstrated a good ability of the KCII to accurately identify impotent patients (on the basis of history) who would have positive or negative signs of hormonal factor or neurological factor confirmed by laboratory results or physical examination. The sample of patients who had significant vascular findings did not allow for adequate comparison with interview findings. The majority of patients had significant psychogenic components to their impotence and might have been incorrectly classified as "solely psychogenic" if they had not been simultaneously evaluated for organic factors. The most important finding was that impotence, in most cases, involved multifactorial etiological components and required a comprehensive evaluation and treatment program.


Infant tracheotomy: results of a survey regarding technique.
To identify practice patterns regarding tracheotomy technique among pediatric otolaryngologists. Survey of physicians. Academic medical center. Members of the American Society of Pediatric Otolaryngology (ASPO) residing in the United States. Physician responses to survey questions, including both multiple choice and free-text responses. We used chi(2) tests to determine if demographic factors (pediatric otolaryngology fellowship training, the number of tracheotomies performed yearly) correlated with differences in the technique used to perform infant tracheotomies. A total of 168 of 225 surveys mailed to ASPO members (75%) were completed and returned. Most respondents (87%) report that they make a simple vertical incision in the trachea. An even greater number (94%) use stay sutures routinely. On other technical points, such as management of the thyroid gland, the subcutaneous fat, and the method of securing the tracheostomy tube, there was much greater variability: 22% of respondents reported having had a serious tracheotomy-related complication in the immediate postoperative period, and 58% of these physicians changed their technique as a result. In several areas, chi(2) analysis revealed statistically significant differences in technique that were dependent on both fellowship training and the number of tracheotomies performed (P < or = .05). Among ASPO members practicing in the United States, there is near-unanimity on certain technical points, with considerable divergence on others. A substantial percentage of our colleagues have experienced a tracheotomy-related complication in the early postoperative period. In many cases, these incidents led to changes in surgical technique.