Homogeneous functional insulin receptor from 3T3-L1 adipocytes. Purification using N alpha B1-(biotinyl-epsilon-aminocaproyl)insulin and avidin-sepharose.
Insulin receptor was purified 10,000-fold from cultured mouse 3T3-L1 adipocytes in 35% overall yield. The specific activities of 125I-insulin binding and autophosphorylation increased in parallel, following the initial Triton X-100 extraction of membranes. The isolation protocol, performed entirely at pH 8.45, entailed adsorption by avidin-Sepharose CL-4B of a complex formed between Triton X-100-solubilized insulin receptor and N alpha B1-(biotinyl-epsilon-aminocaproyl)insulin, and the specific elution of the complex with biotin. The avidin-Sepharose CL-4B was a partially denatured preparation, showing estimated dissociation constants of 0.2 microM for biotin and approximately 1 microM for the bifunctional ligand at, pH 7, 4 degrees C. The bifunctional ligand was characterized by 70% competency in binding to avidin, 100% competency in binding to solubilized insulin receptor, full stimulation of autophosphorylation of the isolated receptor, and maximal stimulation of hexose uptake by intact 3T3-L1 adipocytes. The insulin binding properties of the insulin receptor were uniform throughout this purification procedure. At pH 8.45, 4 degrees C, an average Kd = 0.72 nM was determined for a single class of noninteracting insulin binding sites. The apparent autophosphorylation of the beta-subunit was also unchanged following affinity chromatography. A single oligomeric structure was established for the purified receptor, composed only of 135,000- and 95,000-Da subunits, whose association was lost by denaturation in the presence of reducing agent. This single structure occurred in the initial Triton X-100 extract. The purified insulin receptor was capable of autophosphorylating the beta-subunit and catalyzed phosphorylation of protein substrates.


Subdural enhancement on postoperative spinal MRI after resection of posterior cranial fossa tumours.
In malignant brain tumours which may disseminate staging, usually by cranial and spinal MRI is necessary. If MRI is performed in the postoperative period pitfalls should be considered. Nonspecific subdural contrast enhancement on spinal staging MRI is rarely reported after resection of posterior fossa tumours, which may be mistaken for dissemination of malignancy. We investigated the frequency of spinal subdural enhancement after posterior cranial fossa neurosurgery in children. We reviewed 53 postoperative spinal MRI studies performed for staging of paediatric malignant brain tumours, mainly infratentorial primitive neuroectodermal tumours 2-40 days after surgery. There was contrast enhancement in the spinal subdural space in seven cases. This was not seen in any of eight patients who had been operated upon for a supratentorial tumour. After resection of 45 posterior cranial fossa tumours the frequency of subdural enhancement was 15.5%. MRI showing subdural enhancement was obtained up to 25 days postoperatively. No patient with subdural enhancement had cerebrospinal fluid (CSF) examinations positive for tumour cells or developed dissemination of disease in the CSF. Because the characteristic appearances of subdural contrast enhancement, appropriate interpretation is possible; diagnosis of neoplastic meningitis should rarely be impeded. Because of the striking similarity to that in patients with a low CSF-pressure syndrome and in view of the fact that only resection of tumours of the posterior cranial fossa, usually associated with obstructive hydrocephalus, was followed by this type of enhancement one might suggest that rapid changes in CSF pressure are implicated, rather the effects of blood introduced into the spinal canal at surgery.


Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics.
Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8-14.7 mm Hg) and stop-flow pressures (40.0-42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY. Maximum TGF pressure response was 28.6% greater in SHR than in the normotensive rats (13.3 vs. 9.5 mm Hg; p less than 0.025). The sensitivity, as estimated from the slope of the feedback curve at the Tp [f'(Tp)] was 87% greater in SHR than in WKY. There was no significant difference between these parameters in WKY and SPRD. The TGF pressure response was biphasic in the 3 groups of halothane anaesthetized rats with a steady state level reached in about 2 min after the change in late proximal microperfusion rate. In inactin anaesthetized rats the sensitivity was 41% lower than in the halothane anaesthetized control group of SPRD, the feedback response was lower, and the feedback curve was displaced to the right with the Tp at 15.9 nl/min, significantly higher than in the control group (p less than 0.001). Although the steady state level also was reached within 2 min, the clearly biphasic pattern of the pressure response was less consistent.


Kinetics and persistence of anti-SARS-CoV-2 neutralisation and antibodies after BNT162b2 vaccination in a Swiss cohort.
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), substantial effort has been made to gain knowledge about the immunity elicited by infection or vaccination. We studied the kinetics of antibodies and virus neutralisation induced by vaccination with BNT162b2 in a Swiss cohort of SARS-CoV-2 naïve (n = 40) and convalescent (n = 9) persons. Blood sera were analysed in a live virus neutralisation assay and specific IgG and IgA levels were measured by enzyme-linked immunoassay and analysed by descriptive statistics. Virus neutralisation was detected in all individuals 2-4 weeks after the second vaccine. Both neutralisation and antibodies remained positive for >4 months. Neutralisation and antibodies showed positive correlation, but immunoglobulin G (IgG) and immunoglobulin A (IgA) seroconversion took place 2-4 weeks faster than neutralisation. Spike-protein specific IgG levels rose significantly faster and were more stable over time than virus neutralisation titres or IgA responses. For naïve but not convalescent persons, a clear boosting effect was observed. Convalescent individuals showed faster, more robust and longer-lasting immune responses after vaccination compared to noninfected persons. No threshold could be determined for spike protein-specific IgG or IgA that would confer protection in the neutralisation assay, implicating the need for a better correlate of protection then antibody titres alone. This study clearly shows the complex translation of antibody data and virus neutralisation, while supporting the evidence of a single dose being sufficient for effective antibody response in convalescent individuals.


[Taurine-activated currents in isolated neurons of the rat cerebellum].
Taurine-activated currents in isolated neurons of the rat cerebellum were studied by voltage and "concentration" clamp methods. They were transmitted by potassium and chloride ions. The dose-response curve with the dissociation constant 2 x 10(-3) mol/l was obtained. The cross-desensitization between taurine and GABA, but not between taurine and glycine was shown. These currents were also blocked by bicucullin and strychnine, but in a different manner.


Comparison of responsiveness of validated outcome measures after surgery for stress urinary incontinence.
We compared the responsiveness of several validated incontinence, pelvic floor and quality of life outcome measures in women undergoing surgery for stress urinary incontinence to assist investigators in selecting appropriate outcomes in future trials of stress urinary incontinence therapy. This is an ancillary analysis of data from a multicenter, randomized trial comparing tension-free vaginal tape and transobturator slings. All patients were asked to complete outcome measures at baseline and again 1 year postoperatively, including Incontinence Severity Index, Pelvic Floor Distress Inventory-Short Form 20, Pelvic Floor Impact Questionnaire-Short Form 7, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire 12, SF-12® and a 3-day bladder diary. They also completed the Patient Global Index of Improvement at 1 year. We assessed the responsiveness of each outcome measure by calculating a standardized response mean and performing receiver operator characteristics curve analysis. Incontinence Severity Index, Pelvic Floor Distress Inventory-Short Form 20, Urinary Distress Inventory-Short Form, Pelvic Floor Impact Questionnaire-Short Form 7 and Urinary Impact Questionnaire-Short Form 7 showed excellent responsiveness (standardized response mean ≥1.0). Using receiver operator characteristics curve data the bladder diary had the greatest ability to discriminate patients who did vs did not improve (area under the curve 0.97). Incontinence Severity Index, Pelvic Floor Distress Inventory-Short Form 20 and Urinary Distress Inventory-Short Form also showed strong responsiveness according to these data (area under the curve greater than 0.7). In this study of women undergoing mid urethral sling surgery for stress urinary incontinence the greatest responsiveness was noted on Incontinence Severity Index, Pelvic Floor Distress Inventory-Short Form 20, Urinary Distress Inventory-Short Form and bladder diary. Thus, they may be preferable as primary outcome measures in trials of stress urinary incontinence treatment.


Shoulder reaction time and muscle-firing patterns in response to an anterior translation force.
The primary restraint preventing humeral head translation is the capsuloligamentous system. Muscle forces can also decrease translation; however, the timing and magnitude of muscle response has not been previously reported. Fine wire electromyographic analysis of the biceps long head, anterior deltoid, pectoralis major, latissimus dorsi, and rotator cuff muscles was performed after an anterior translation force was applied to 15 normal shoulders. The reflex response time (time to 5% maximal muscle test), the protection response time (time to 20% maximal muscle test), the duration of the protection response, and the magnitude of the protection response were calculated. The shoulder reaction data showed 2 consistent patterns. Activation of the anteriorly located muscles preceded the posteriorly located muscles, and the rotator cuff muscles fired with greater magnitude than the more peripherally located muscles.


Synthesis, molecular docking and kinetic properties of β-hydroxy-β-phenylpropionyl-hydroxamic acids as Helicobacter pylori urease inhibitors.
Inhibition of urease results in Helicobacter pylori growth arrest in the stomach, promoting urease as promising targets for gastrointestinal ulcer therapy. Twenty hybrid derivatives of flavonoid scaffold and hydroxamic acid, β-hydroxy-β-phenylpropionylhydroxamic acids, were therefore synthesized and evaluated against H. pylori urease. Biological evaluation of these compounds showed improved urease inhibition exhibiting micromolar to mid-nanomolar IC50 values. Most importantly, 3-(3-chlorophenyl)-3-hydroxypropionyl-hydroxamic acid (6g) exhibited high potency with IC50 of 0.083±0.004 μM and Ki of 0.014±0.003 μM, indicating that 6g is an excellent candidate to develop novel antiulcer agent. A mixture of competitive and uncompetitive mechanism was putatively proposed to understand the inconsistency between the crystallographic and kinetic studies for the first time, which is supported by our molecular docking studies.


Laser propulsion of nanobullets by adiabatic compression of surface plasmon polaritons.
Laser propulsion and guide of nanosized objects is fundamental for a wide number of applications. These applications are often limited by the fact that the optical forces acting on nanoparticles are almost negligible even in the favorable case of metallic particles and hence large laser powers are needed to accelerate and guide nanosize devices in practical applications. Furthermore, metallic nanoparticles exhibit strong absorption bands and scattering and this makes more difficult controlling nanopropulsion. Thus, finding some mechanism enhancing the optomechanical interaction at the nanoscale controlled by laser is specifically challenging and pivotal. Here, we demonstrate a novel physical effect where the well-known adiabatic localization of the enhanced plasmonic surface field on the apex of metallic nanocones produces a significant optical pressure employable as a propulsive mechanism. The proposed method gives the possibility to develop new photonics devices to accelerate metallic nanobullets over long distances for a variety of applications.


Influence of the material removal mechanisms on hole integrity in ultrasonic machining of structural ceramics.
Micro-chipping via micro-cracks, due to rapid mechanical indentations by abrasive grits, is the fundamental mechanism of material removal during ultrasonic machining (USM) of hard-brittle materials like ceramics and glass. This study aims mainly to investigate the adverse effects of this inherent removal phenomena on the hole integrity such as entrance chipping, wall roughness and subsurface damage. It also presents the material removal mechanism happens in the gap between the tool periphery and the hole wall (called 'lateral gap'). To do so, experiments were conducted for drilling holes on three advanced structural ceramics, namely, silicon carbide, zirconia, and alumina. Earlier published basic studies on the initiation of different crack modes and their growth characteristics are employed to explain the experimental findings in this USM study. It is realized that the radial and the lateral cracks formed due to adjacent abrasives, which are under the tool face, extends towards radial direction of the hole resulting in entrance chipping. Additionally, the angle penetration and the rolling actions of the abrasives, which are at the periphery of the tool, contribute to the entrance chipping. Later on, in the 'lateral gap', the sliding (or abrasion) and the rolling mechanisms by the larger abrasives take part to material removal. However, they unfavorably produce micro-cracks in the radial direction resulting in surface and subsurface damages, which are ultimately responsible for higher wall-surface roughness. Since the size of micro-cracks in brittle materials is grit size dependent according to the earlier studied physics, it is realized that such nature of the hole integrity during USM can only be minimized by employing smaller grit size, but cannot fully be eliminated.


Identification of antigenic epitopes in type IV collagen by use of synthetic peptides.
Peptides representing potential antigenic regions of the NC-1 and 7-S domains of the human alpha 1 and alpha 2, and bovine alpha 3 chains of type IV collagen were synthesized either chemically or by the recombinant DNA technique and tested by ELISA using antibodies raised in rabbits against the whole type IV collagen or the NC-1 domain. Sera from patients with Goodpasture syndrome (GP) or with acute poststreptococcal glomerulonephritis (APSGN) were also tested. The location of antigenic determinants was predicted from the primary and secondary structure of the chains, that is, aromaticity, hydrophilicity and presence of beta-turns. All synthetic peptides reacted with the antiserum to type IV collagen (anti-Col IV). Whereas all peptides arising from the NC-1 domain reacted with anti-NC-1, intact 7-S or peptides of the alpha 1 or alpha 2 chain of the 7-S domain did not react. However intact 7-S reacted with anti-Col IV. Two synthetic peptides from the NC-1 domain of alpha 1, (a.a. 71-90 and a.a. 176-190), one from the alpha 2 (a.a. 70-83) and four from the alpha 3 chain (a.a. 72-89, a.a. 104-117, a.a. 133-145, a.a. 185-203) reacted with anti-NC-1 and anti-COL IV. The above peptides, except alpha 3 (72-89) and alpha 3 (185-203), were tested and found to be reactive with sera from patients with GP.(ABSTRACT TRUNCATED AT 250 WORDS)


[Vestibulofugal projections to the lateral reticular nucleus of the cat medulla].
Certain amount of neurons in vestibular nuclei were labelled after horseradish peroxidase injection in the medullar lateral reticular nucleus of cat. Such projections were strictly homolateral and formed by small and medium-size neurons localized mainly in the Deiters nucleus; their number was, probably, much less in comparison with the number of vestibulo-spinal units. Functional role of vestibular projections to the lateral reticular nucleus in the motor activity control is discussed.


Induced periosteum a complex cellular scaffold for the treatment of large bone defects.
Surgically induced periosteal membrane holds great potential for the treatment of large bone defects representing a simple alternative to combinations of exogenous stem cells, scaffolds and growth factors. The purpose of this study was to explore the biological basis for this novel regenerative medicine strategy in man. Eight patients with critical size defects were treated with the induced membrane (IM) technique. After membrane formation 1cm(2) biopsy was taken together with matched, healthy diaphyseal periosteum (P) for comparative analysis. Morphological characteristics, cell composition and growth factor expression were compared. Functional and molecular evaluation of mesenchymal stromal cell (MSC) activity was performed. Both tissues shared similar morphology although IM was significantly thicker than P (p=0.032). The frequency of lymphocytes, pericytes (CD45(-)CD34(-)CD146(+)) and cells expressing markers consistent with bone marrow MSCs (CD45(-/low)CD271(bright)) were 31. 3 and 15.5-fold higher respectively in IM (all p=0.043). IM contained 3-fold more cells per gramme of tissue with a similar proportion of endothelial cells (CD45(-)CD31(+)). Expressed bone morphogenic protein 2, vascular endothelial growth factor and stromal derived factor 1 (SDF-1) are key tissue regeneration mediators. Adherent expanded cells from both tissues had molecular profiles similar to bone marrow MSCs but cells from IM expressed greater than 2 fold relative abundance of SDF-1transcript compared to P (p=0.043). The IM is a thick, vascularised structure that resembles periosteum with a cellular composition and molecular profile facilitating large defect repair and therefore may be described as an "induced-periosteum". This tissue offers a powerful example of in situ tissue engineering.


New Miyake-Apple View system using a nasal endoscope.
To evaluate images and videos behind the anterior segment of cataract surgery with the porcine eye using a new Miyake-Apple View with a nasal endoscope. Sugiura Eye Clinic, Fuji, Shizuoka, Japan. Laboratory study. A hole was made in a commercially available wooden desk and the nasal endoscope was fixed under the desk. A tunnel for passing the probe of the nasal endoscope was opened on a Styrofoam human-faced base, and the probe was passed through. A 3 mm × 3 mm incision was made behind the globe, and a nasal endoscope probe was inserted to observe the posterior anterior segment of the eye. The posterior part of the anterior segment of the eye could be clearly observed, and each procedure (hydrodissection, phacoemulsification, irrigation and aspiration, and insertion and fixation of intraocular lens [IOL]) in normal cataract surgery could be observed from the posterior. Lighting could be improved. The conventional Miyake-Apple View required a large-scale custom-made device, which was expensive and could not be taken easily, and required to cut the globe and a technique to fix it to the glass plate. However, this method made it easy to prepare for shooting, and the equipment was inexpensive. Furthermore, it had the great advantage of not having to cut the globe. Since the integrity of the globe was maintained, normal cataract surgery could be reproduced and dynamic observation from the back became possible. It was useful for practicing cataract surgery and examining the fixed state of new IOLs.


Blood flow, vascular resistance and oxygen availability in malignant tumours upon intravenous flunarizine.
Tumour blood flow, an important determinant of the efficacy of presently available nonsurgical cancer treatments, significantly increased following a single I.V. injection of the calcium antagonist flunarizine. At a dose of 1 mg/kg, tumour blood flow increased approximately by 28% without a significant change in mean arterial blood pressure. The flow increase was paralleled by a similar improvement of the O2 availability to the cancer cells. The data suggest that flunarizine may provide a means of improving delivery of antineoplastic agents to tumours. Furthermore, flunarizine may also enhance the effectiveness of irradiation by increasing tumour oxygenation.


The Effect of Herbal Feed Additives in the Diet of Dairy Goats on Intestinal Lactic Acid Bacteria (LAB) Count.
Sixty dairy goats of the Polish white improved breed were randomly assigned to five feeding groups of twelve animals each. The animals received a supplement containing seven herbs at 20 or 40 g/animal/day (experimental groups 1 and 2) and a supplement containing nine herbs at 20 or 40 g/animal/day (experimental groups 3 and 4)m, along with pelleted concentrate feed. Group 5 (the control group) received pelleted feed without any herbal supplements. A significant effect of herbal feed additive on lactic acid bacteria (LAB) count was observed (p < 0.001). The highest number density of LAB was found in the goats receiving the feed additive with nine herbs at 20 g/animal per day (p < 0.05). There was a statistically significant effect of lactation stage on intestinal LAB count (p < 0.001). Regardless of the feeding group, the highest number density of LAB was found in animals at the peak of lactation. The LAB count was also affected by the interaction of diet group × lactation stage (p < 0.0001). A probiotic strain of Lactobacillus fermentum was identified in the faecal samples of goats receiving the herbal additive, but not in the controls. Genetic identification of the microorganisms isolated from the faeces of the experimental goats did not reveal the presence of harmful mould spores, although spores of the fungus Aspergillus fumigatus were detected in the controls.


Percutaneous revascularization of long femoral artery lesions for claudication: patency over 2.5 years and impact of systematic surveillance.
Angioplasty and stenting are preferred treatments for revascularizing femoral artery lesions up to 100 mm, but surgical bypass is recommended for longer lesions. We assessed long-term patency after percutaneous revascularization of long femoral artery lesions for claudication with intensive out-patient surveillance. We followed a cohort of 111 consecutive patients receiving angioplasty or stenting in 142 limbs in two institutions. Patients were followed for 2.5 years, and event curves and multivariable survival analysis used to compare outcomes in three groups according to lesion length (< 100 mm, 100-200 mm, and greater than 200 mm). Failed patency was defined as recurrence of symptoms with a decline in ankle brachial index, or stenosis identified by duplex ultrasound, or reintervention. Compared to lesions less than 100 mm, longer lesions had higher failed primary patency (100-200 mm: HR = 2.0, P = 0.16, >200 mm: HR = 2.6, P = 0.03). Failed secondary patency was similar for short and intermediate lesions (< 5% incidence), but trended higher for lesions >200 mm (HR = 4.2, P = 0.06). An initial procedure residual stenosis greater than 20% was the only significant multivariable factor related to poorer long-term patency (HR = 15.8, P = 0.003). Compared to short lesions, the gain in long-term patency with out-patient surveillance and reintervention was higher for longer lesions and significantly so for intermediate lesions (100-200 mm = 23% versus <100 mm = 8%, P = 0.041). Percutaneous treatment of long femoral artery lesions can provide acceptable long-term patency for patients with claudication when out-patient surveillance is used to identify patients who require repeat interventions. Future long-term studies should consider overall patency encompassing more than one percutaneous reintervention.


Synthesis of fused polycyclic β-carboline derivatives using Ugi-4CR followed by cascade cyclization.
Ugi-four component reaction (Ugi-4CR) is extremely attractive for diversity-oriented and step economical synthesis as evident from past applications. Here we report the synthesis of fused polycyclic β-carboline derivatives by sequential Pictet-Spengler's and Ugi-4CR multi-component reaction followed by cascade cyclization. The post cyclisation of Ugi product provides conformationally stable heterocyclic molecule that is expected to be suitable for interaction with different biological targets. The methodology provides a simple and facile access to heterocycles embedded in polycyclic framework which otherwise seems difficult to synthesize by conventional methods. Synthesis of fused Polycyclic β-Carboline Derivatives Using Ugi-4CR Followed by Cascade Cyclization.


In human monocytes a strong correlation exists between expression of the M3 antigen, Fc-mediated phagocytic activity and failure to participate in extracellular antibody-dependent cytotoxicity.
Human fresh blood monocytes can phagocytize and lyse antibody-coated target cells by contact with membrane Fc receptors. Recently, the monocyte differentiation antigen Leu M3 has been described to be associated with monocyte/macrophage maturation pathway and to be linked to functionally distinct monocyte subsets. In the present study peripheral blood monocytes were separated into M3+ and M3- subsets, and evaluated for their ability to mediate antibody-driven effector functions. A clear cut functional difference could be demonstrated. M3+ monocytes phagocytize antibody-coated sheep red cells but do not carry out contact-mediated extracellular lysis. In contrast, M3- monocytes have exactly the opposite functional features and they mediate cytolysis without exhibiting any phagocytic activity. By using phenotypically defined clones of the U937 histiocytic cell line, the segregation of different lytic abilities and their linkage of the M3 phenotype have been confirmed.


Comparison of antiviral compounds against human herpesvirus 6 and 7.
Four classes of antiviral compounds were evaluated for inhibitory activity against two variants of human herpesvirus 6 (HHV-6A and -6B) and human herpesvirus 7 (HHV-7). These included: (1) a pyrophosphate analog, phosphonoformic acid (PFA); (2) beta-guanine analogs, 9-(2-hydroxyethoxymethyl)guanine (acyclovir or ACV), 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir or GCV) and 9-(4-hydroxy-3-hydroxy-3-hydroxymethylbutylyl)guanine (penciclovir or PCV); (3) acyclic nucleoside phosphonates, (S)-1-[(3-hydroxy-2-phosphonylmethoxy)propyl]cytosine [cidofovir or (S)-HPMPC] and its cyclic derivative (S)-cyclic-HPMPC (cHPMPC), 9-[[2-hydroxy-1-phosphonomethoxy)ethoxy]methyl]guanine (HPMEMG) and 9-[(2-phosphonylmethoxy)ethyl]-2,6-diaminopurine (PMEDAP), and the seven other related compounds; and (4) a series of benzimidazole ribonucleosides, including 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB). End-point inhibitory concentration (EPC) and 50% effective inhibitory concentration (EC50) values were determined by a dot-blot antigen detection method in cord blood mononuclear cells infected with HHV-6A, HHV-6B or HHV-7 at a multiplicity of infection of 0.004 CCID50/cell. (S)-HPMPC and cHPMPC had an EC50 value of approximately 0.3 microg/ml for HHV-6A, 1.2 microg/ml for HHV-6B and 3.0 microg/ml for HHV-7. These compounds were the most active of those tested against each virus. The EC50 value of GCV for HHV-6A was 0.65 microg/ml, 1.33 microg/ml for HHV-6B, and >7 microg/ml for HHV-7. The EC50 values of ACV and PCV were approximately 6-8 microg/ml for HHV-6A, 16-24 microg/ml for HHV-6B and 121-128 microg/ml for HHV-7. These drugs were the least active. The sensitivity of HHV-7 to the guanine analogs was different from HHV-6, suggesting a difference in selectivity of specific viral enzymes.


Painless bilateral visual loss in a 33-year-old woman with severe arterial hypotension.
A 32-year-old woman experienced dizziness and headache for 5 months. She also complained of painless, progressive bilateral visual loss for several weeks. Before developing the initial symptoms, she had an uncomplicated pregnancy except for dizziness and systemic hypotension during the first term. Fundus examination disclosed prominent retinal arteries as well diffuse microaneurysms, widespread intraretinal hemorrhages, and hyperemic optic disks. Brain magnetic resonance imaging revealed multiple supratentorial white-matter lesions suggestive of ischemic strokes. Initially, she had severe systemic hypotension (41/17 mm Hg). When reassessed, blood pressure was normal in the lower limbs, but there was severe hypotension in the upper limbs. An angio-computed tomography of the supraortic trunks showed occlusion of both primitive carotid arteries, both subclavian arteries and the right axillary and humeral arteries. Based on these findings, the diagnosis of Takayasu type-I arteritis with ischemic retinopathy and cerebrovascular disease was established. Bilateral retinal panphotocoagulation and aorta to right carotid bypass were performed because of the severity of the ischemic lesions.


Successful use of culture and enrichment for the detection of OXA-181-producing Escherichia coli from rectal swab samples falsely categorized as negative by Xpert® Carba-R.
An OXA-181 producing Escherichia coli isolate that went recurrently undetected directly from rectal swab sample using Xpert® Carba-R, was successfully detected using ertapenem supplemented broth enrichment followed by culture-based method. Our data suggest that implementation of culture-based methods plus enrichment might be crucial for the efficient screening of patients considered to be at "high-risk" of colonization with carbapenemase producers and who are colonized at low level.


Construct validity of the Levels of Emotional Awareness Scale among women high in eating disorder symptoms: a cross-sectional study.
The Levels of Emotional Awareness Scale (LEAS), a measure of the ability to identify and describe one's own and others' emotions, may complement work with women with disordered eating symptoms. The study purpose was to (a) examine differences in hand (LEAS) versus computerized (e-LEAS) scoring methods and (b) examine the e-LEAS' psychometric properties, including convergent and discriminant validity, among women endorsing eating disorder symptoms. Forty women (ages 18-21) scoring high on a self-report measure of disordered eating symptoms completed the LEAS and measures of convergent validity including a self-report measure of alexithymia (the perceived ability to identify and describe one's own emotions) and a measure of facial affect recognition as well as discriminant validity, including affect and facial memory. Inter-rater reliability was assessed via a two-way mixed effects model and correlations between the LEAS and the study constructs were examined. Computerized scoring (e-LEAS) offered benefits over hand scoring and correlations between LEAS and e-LEAS were statistically significant. Better total emotional awareness scores on the e-LEAS were significantly associated with more perceived difficulty identifying and describing emotions. Better total emotional awareness scores were also significantly associated with better facial memory and greater depression scores. The e-LEAS showed weak associations with facial affect recognition. The e-LEAS offers practical advantages over the LEAS in the assessment of emotional awareness among women endorsing eating disorder symptoms. Results suggest that the e-LEAS measures the ability to describe emotional experiences in oneself and others, but not facial affect recognition. Level V: Evidence obtained from a cross-sectional descriptive study.


Generic Language Use Reveals Domain Differences in Children's Expectations about Animal and Artifact Categories.
The goal of the present study was to explore domain differences in young children's expectations about the structure of animal and artifact categories. We examined 5-year-olds' and adults' use of category-referring generic noun phrases (e.g., "Birds fly") about novel animals and artifacts. The same stimuli served as both animals and artifacts; thus, stimuli were perceptually identical across domains, and domain was indicated exclusively by language. Results revealed systematic domain differences: Children and adults produced more generic utterances when items were described as animals than artifacts. Because the stimuli were novel and lacking perceptual cues to domain, these findings must be attributed to higher-order expectations about animal and artifact categories. Overall, results indicate that by age 5, children are able to make knowledge-based domain distinctions between animals and artifacts that may be rooted in beliefs about the coherence and homogeneity of categories within these domains.


Biomonitoring metal deposition in Galicia (NW Spain) with mosses: factors affecting bioconcentration.
Three factors (canopy effect, lithology and seasonal variations) that may influence the concentrations of metals in terrestrial mosses were studied. The levels of 17 elements were determined in terrestrial mosses (Scleropodium purum (Hedw.) Limpr, and Hypnum cupressiforme Hedw.) collected from 75 sites in Galicia at two sampling times, in 1995 and 1997. In addition, monthly samples of S. purum were collected throughout a period of one year from four sites in the same area, for analysis of levels of eight elements. The first studied factor, collection of mosses from areas under tree cover, did not influence significantly the levels of the elements analysed. The second factor studied was the dominant lithology in the sampling area (granite, slate and schist). No significant differences were found between samples from sites where granites and slates dominated. Significant differences were found in the levels of Co, Cr, Ni and Mn in both species growing in granite and slate substrate areas when compared with those growing in schist areas. This was also found for Al and Fe in S. purum and for As in H. cupressiforme. The third factor investigated, using the results from the monthly survey, was the seasonal effect. No significant differences were found in the concentrations of all elements in S. purum throughout the year.


Alterations in gastric mucus secretion in rhesus monkeys after exposure to ionizing radiation.
The aim of the present study was to evaluate the effect of gamma-irradiation on soluble gastric mucus. Six conscious chair-adapted rhesus monkeys were studied once before and twice after exposure to ionizing irradiation (800 rads). Using a marker (99mTc-DTPA) dilution technique, acidic glycoprotein (AG), neutral glycoprotein (NG), ion, and fluid output were determined during a basal period and after the administration of an 80-ml water load. Irradiation significantly increased the outputs of both AG and NG during the basal period. After the water load, NG output remained elevated but irradiation abolished postload AG output thus inhibiting the normal rise in AG output stimulated by the load. Two days after irradiation NG output had returned to control levels whereas AG output was still suppressed. Sodium and potassium ion outputs were unaltered by irradiation. Chloride and fluid outputs were significantly inhibited on the day of irradiation but had returned to control levels within 3 days. These results indicate that irradiation produces significant changes in both the quantity and nature of the soluble mucus glycoproteins secreted into the gastric juice. It is suggested that these changes may compromise the protective ability of gastric mucus.


Antiapoptosis and mitochondrial effect of pioglitazone preconditioning in the ischemic/reperfused heart of rat.
Pioglitazone, used clinically in the treatment of type 2 diabetes mellitus, has been implicated as a regulator of cellular inflammatory and ischemic responses. The present study examined whether pioglitazone could inhibit cardiomyocyte apoptosis and reduce mitochondrial ultrastructure injury and membrane potential loss in the ischemic/reperfused heart of the rat. Furthermore, we investigated whether the protective effect of pioglitazone was related to opening of the mitochondrialATP-sensitive potassium channels. Adult male Sprague-Dawley rats were subjected to 30 min of ischemia followed by 4 h of reperfusion. At 24 h before ischemia, rats were randomized to receive 0.9% saline, 5-hydroxydecanoate (5-HD, 10 mg kg(-1), i.v.) plus pioglitazone (3 mg kg(-1), i.v.) or pioglitazone (3 mg kg(-1), i.v.). One group served as sham control. We investigated mitochondrial structure, apoptosis rate and Bcl-2, Bax and Caspase-3 proteins by immunohistochemistry staining. RT-PCR was used to determine the expression of P38MAPKmRNA and JNKmRNA. Western blotting was used to measure the expression of P38MAPK, JNK and NFkappaB P65. A second group of rats were randomly divided into sham-operated, ischemia/reperfusion (I/R), pioglitazone treatment, 5-HD + pioglitazone and 5-HD groups and the size of myocardial infarction was determined. Primary cultured cardiomyocytes of neonatal Sprague-Dawley rats were divided into control, hypoxia reoxygenation, different concentrations of pioglitazone and 5-HD + pioglitazone groups. JC-1 staining flowcytometry was used to examine mitochondrial membrane potential (DeltaPsim). Pioglitazone decreased mitochondrial ultrastructural damage compared to I/R, and reduced infarct size from 34.93 +/- 5.55% (I/R) to 20.24 +/- 3.93% (P < 0.05). Compared with the I/R group, the apoptosis rate and positive cell index (PCI) of Bax and Caspase-3 proteins in the pioglitazone group were significantly decreased (P < 0.05), while the PCI of Bcl-2 protein was increased (P < 0.05). There was no significant difference between the I/R and 5-HD + pioglitazone groups. Compared with the sham-operated group, the expression of P38MAPK mRNA, JNK mRNA and protein of P38MAPK, JNK and NFkappaB P65 in I/R was increased (P < 0.05). Pioglitazone did inhibit the increase in expressions vs I/R (P < 0.05). The rate of loss DeltaPsim cells in the pioglitazone group was significantly lower than in the hypoxia reoxygenation group, while the addition of 5-HD inhibited the effect of pioglitazone. Pioglitazone inhibited cardiomyocyte apoptosis and reduced mitochondrial ultrastructure injury and membrane potential loss in the ischemic/reperfused heart of rat. These protective effects of pioglitazone may be related to opening mitochondrial(ATP)-sensitive potassium channels.


Identification of a novel bile marker clusterin and a public online prediction platform based on deep learning for cholangiocarcinoma.
Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor, and its diagnosis is still a challenge. This study aimed to identify a novel bile marker for CCA diagnosis based on proteomics and establish a diagnostic model with deep learning. A total of 644 subjects (236 CCA and 408 non-CCA) from two independent centers were divided into discovery, cross-validation, and external validation sets for the study. Candidate bile markers were identified by three proteomics data and validated on 635 clinical humoral specimens and 121 tissue specimens. A diagnostic multi-analyte model containing bile and serum biomarkers was established in cross-validation set by deep learning and validated in an independent external cohort. The results of proteomics analysis and clinical specimen verification showed that bile clusterin (CLU) was significantly higher in CCA body fluids. Based on 376 subjects in the cross-validation set, ROC analysis indicated that bile CLU had a satisfactory diagnostic power (AUC: 0.852, sensitivity: 73.6%, specificity: 90.1%). Building on bile CLU and 63 serum markers, deep learning established a diagnostic model incorporating seven factors (CLU, CA19-9, IBIL, GGT, LDL-C, TG, and TBA), which showed a high diagnostic utility (AUC: 0.947, sensitivity: 90.3%, specificity: 84.9%). External validation in an independent cohort (n = 259) resulted in a similar accuracy for the detection of CCA. Finally, for the convenience of operation, a user-friendly prediction platform was built online for CCA. This is the largest and most comprehensive study combining bile and serum biomarkers to differentiate CCA. This diagnostic model may potentially be used to detect CCA.


Four new species of the genus Luzonomyza Malloch (Diptera, Lauxaniidae) from China.
Four species of the genus Luzonomyza Malloch, 1929 from southwest China are described as new to science: Luzonomyzavittifacies Li & Yang, sp. nov., L.serrata Li & Yang, sp. nov., L.honghensis Li & Yang, sp. nov., and L.brevis Li & Yang, sp. nov. A key to Luzonomyza species is also presented.


Pure retroperitoneal natural orifice translumenal endoscopic surgery (NOTES) transvaginal nephrectomy using standard laparoscopic instruments: a safety and feasibility study in a porcine model.
Among the different organs used for NOTES (natural orifice translumenal endoscopic surgery) technique, the transvaginal approach may be the optimal choice because of a simple and secure closure of colpotomy site. Pure and hybrid NOTES transvaginal operations were routinely performed via transperitoneal access. In this study, we investigate the safety and feasibility of pure retroperitoneal natural orifice translumenal endoscopic surgery (NOTES) transvaginal nephrectomy using conventional laparoscopic techniques in a porcine model. Six female pigs, weighing an average of 30 kg, were used in this study. Under general anesthesia, pure retroperitoneal NOTES transvaginal nephrectomy was conducted using standard laparoscopic instruments. Posterolateral colpotomy was performed, and the incision was enlarged laterally using blunt dissection and pneumatic dilation. A single-port device was inserted to construct the operative channel. The retroperitoneal space was created using sharp and blunt dissection under endoscopic guidance up to the level of the kidney. Dissection and removal of the kidney were performed according to standard surgical procedure, and the colpotomy site was closed using interrupted sutures. The survival and complications were observed 1 week postoperatively. Our results showed that two cases failed because of peritoneal rupture. One case was successful, but required the assistance of an extra 5 mm laparoscopic trocar inserted in the flank. Three cases of pure retroperitoneal NOTES transvaginal nephrectomy were completed, and survived 1 week after the operation. In these three cases, no intra- or postoperative complications were observed. All findings confirmed the safety and feasibility of the retroperitoneal pure retroperitoneal NOTES transvaginal nephrectomy using standard laparoscopic instruments, which suggested the possibility of clinical application in human beings in the future.


Systemic administration of STING agonist promotes myeloid cells maturation and antitumor immunity through regulating hematopoietic stem and progenitor cell fate.
STING is a pivotal mediator of effective innate and adaptive anti-tumor immunity; however, intratumoral administration of STING agonists have shown limited therapeutic benefit in clinical trials. The systemic effect of the intravenous delivery of STING agonists in cancer is not well-defined. Here, we demonstrated that systemic administration of STING agonist inhibited melanoma growth, improved inflammatory effector cell infiltration, and induced bone marrow mobilization and extramedullary hematopoiesis, causing widespread changes in immune components in the peripheral blood. The systemically administered STING agonist promoted HSC expansion and influenced lineage fate commitment, which was manifested as the differentiation of HSPCs was skewed toward myeloid cells at the expense of B-cell lymphopoiesis and erythropoiesis. Transcriptome analysis revealed upregulation of myeloid lineage differentiation-related and type I interferon-related genes. This myeloid-biased differentiation promoted the production and maturation of myeloid cells toward an activated phenotype. Furthermore, depletion of Gr-1+ myeloid cells attenuated the anti-tumor immunity of STING agonist. Our findings reveal the anti-tumor mechanism of systemic administration of STING agonist that involves modulating HSPC differentiation and promoting myeloid cells maturation. Our study may help explain the limited clinical activity of STING agonists administered intratumorally.


Would pulsed radiofrequency applied to different anatomical regions have effective results for chronic pain treatment?
To observe the effect of Pulsed radiofrequency on patients presenting with complaints of chronic pain. It was a retrospective cross sectional study which included patients with chronic pain who did not respond to conventional treatment.The study was conducted at the Pain Management Centre, Dicle University, Diyarbakir, Turkey from October 2008 to September 2010. The applications of Pulsed radiofrequency (PRF) were made under the guidance of C-arm fluoroscopy, local anaesthesia, and sedoanalgesia. The intervention types applied consisted of sacroiliac intraarticular, heel, sciatic nerve and impar ganglion Pulsed radiofrequency. Visual Analogue Scale (VAS) was used for pain assessment.Sacroiliac intraarticular PRF was applied to nine patients, impar ganglion PRF to eight patients, heel PRF to four patients and sciatic nerve PRF was applied to three patients. The mean age of the patients was 41.3 +/- 16.9 (range 15-77) years, 15 (62.5%) were females. The mean follow-up period was 8.5 +/- 5.4 months. A minimum 50% decrease was determined in the VAS scores of 16 (66.7%) patients compared to the initial values. The patients who had > or = 50% decrease in their VAS scores in the sacroiliac group was 55.6. This value was 75.0, 75.0 and 66.7 in the impar, heel and sciatic nerve groups respectively. No early- or late-term complications were observed in any of the patients. P Pulsed Radiofrequency implementation was found to be an effective and safe method for chronic pain treatment in our centre.


Localization of human c-mos to chromosome band 8q11 in leukemic cells with the t(8;21) (q22;q22).
Chromosome in situ hybridization studies locate c-mos to chromosome band 8q11 in leukemic cells carrying the t(8;21) (q22;q22). This amends the previous assignment of c-mos to chromosome band 8q22 and conforms with its recent assignment to 8q11 in normal cells and in a cell line with a structurally abnormal chromosome 8. C-mos lies proximally to, and distant from, the breakpoint at 8q22 in the t(8;21) and is unlikely to have a role in the onset of acute myeloid leukemia characterized by this translocation.


Improving prediction of drug-target interactions based on fusing multiple features with data balancing and feature selection techniques.
Drug discovery relies on predicting drug-target interaction (DTI), which is an important challenging task. The purpose of DTI is to identify the interaction between drug chemical compounds and protein targets. Traditional wet lab experiments are time-consuming and expensive, that's why in recent years, the use of computational methods based on machine learning has attracted the attention of many researchers. Actually, a dry lab environment focusing more on computational methods of interaction prediction can be helpful in limiting search space for wet lab experiments. In this paper, a novel multi-stage approach for DTI is proposed that called SRX-DTI. In the first stage, combination of various descriptors from protein sequences, and a FP2 fingerprint that is encoded from drug are extracted as feature vectors. A major challenge in this application is the imbalanced data due to the lack of known interactions, in this regard, in the second stage, the One-SVM-US technique is proposed to deal with this problem. Next, the FFS-RF algorithm, a forward feature selection algorithm, coupled with a random forest (RF) classifier is developed to maximize the predictive performance. This feature selection algorithm removes irrelevant features to obtain optimal features. Finally, balanced dataset with optimal features is given to the XGBoost classifier to identify DTIs. The experimental results demonstrate that our proposed approach SRX-DTI achieves higher performance than other existing methods in predicting DTIs. The datasets and source code are available at: https://github.com/Khojasteh-hb/SRX-DTI.


Endoscopic management of low output recurrent colonic fistula or leak after anterior resection for rectal cancer: a randomized controlled trial.
Colonic anastomotic leak and fistula following anterior resection surgery for rectal cancer are associated with high mortality rates. The incidence of occurrence varies from 2 to 25% and it is difficult to accurately calculate the incidence of fistula and leak post anterior resection, as most of them are asymptomatic. Endoscopic management of fistula and leak has become the first line of management after conservative management in many gastrointestinal surgical centers with the advantages of being less invasive, shorter length of post-operative hospital stay, effective and rapid recovery in comparison to revision surgery. Effective endoscopic management for colonic fistula or leak depends on the clinical status of the patient and fistula characters (time-to-occur and size and site of defect), and device availability. This prospective randomized controlled clinical trial included all patients who developed the manifestations of low output recurrent colonic fistula or leak after colonic anterior resection for rectal cancer at Zagazig University Hospital between (December 2020 and August 2022). Sample size was 78 patients divided into two equal groups. Endoscopic group (EG): included 39 patients who underwent endoscopic management. Surgical group (SG): included 39 patients who underwent surgical management. The investigators randomized eligible 78 patients into two groups: 39 patients in SG and 39 patients in EG. The median size of the fistula or leak was nine (range: 7-14) mm in EG, versus ten (range: 7-12) mm in SG. Clipping and Endo-stitch device were used in 24 patients versus 15 patients, respectively, in EG while primary repair with ileostomy, and resection & anastomosis were used in 15 patients versus 24 patients, respectively, in SG. Recurrence, abdominal collection, and mortality were the post procedure's complications with incidence of occurrence of 10.3, 7.7 and 0%, respectively, in EG versus 20.5, 20.5 and 2.6%, respectively, in SG. Excellent, good, and poor were the parameters for quality of life with incidence of occurrence of 43.6, 54.6 and 0%, respectively, in EG versus 28.2, 33.3 and 38.5%, respectively, in SG. Median hospital stay was one (range: 1-2) day in endoscopic group, and seven (range: 6-8) days in SG. Endoscopic intervention may offer a successful modality in managing low output recurrent colonic fistula or leak after anterior resection for rectal cancer that did not respond to conservative measures in stable patients. gov ID: NCT05659446.


Full retraction: Rajendra S. Kadam, Jason Williams, Puneet Tyagi, Henry F. Edelhauser, Uday B. Kompella. Suprachoroidal delivery in a rabbit ex vivo eye model: influence of drug properties, regional differences in delivery, and comparison with intravitreal and intracameral routes. Mol Vis. 2013; 19:1198-1210.
[This retracts the article on p. 1198 in vol. 19, PMID: 23734089.].


[Influence of different obstetric-manipulations on the continuous measured pO2-tension upon the fetus sub partu (author's transl)].
The influence of different obstetric-manipulations and medicamental applications was investigated in regard of the continuous measured fetal intrauterine pO2-tension sub partu. By demonstrating some original registrations it was intended to point out the efficiency of these obstetric-manipulations.


The ecogenotoxic plant biomonitoring of a long-term polluted area in central Slovakia.
The aim of the study was to analyze, update, and complete the results of research in the field of in situ phytoindication of environmental genotoxicity near the aluminum plant in Žiar nad Hronom in central Slovakia. The authors focused on two methodologies: pollen abortivity assay of native flora and Trad-MCN assay. Comparison of changes in responses of living systems to changes in precipitation was conducted, and it suggests that there is an existence of an impact from a dilution effect to the plants. Also, the gradual increase of pollen abortivity in the 1990s and its decrease from 2009 were observed in a majority of species of wild flora. On an annual basis, abortivity has declined, although it has risen up slightly within each season. Despite a gradual decrease in the micronucleus frequency, the study area is still influenced by the ecogenotoxic factors. Pollen analysis of native flora and introduced Tradescantia plants indicates the long-time presence of ecogenotoxicity in this region due to the presence of aluminum plant.


Complete genomes and comparative analyses of Streptomyces phages that influence secondary metabolism and sporulation.
Bacteria in the genus Streptomyces are found ubiquitously in nature and are known for the number and diversity of specialized metabolites they produce, as well as their complex developmental lifecycle. Studies of the viruses that prey on Streptomyces, known as phages, have aided the development of tools for genetic manipulation of these bacteria, as well as contributing to a deeper understanding of Streptomyces and their behaviours in the environment. Here, we present the genomic and biological characterization of twelve Streptomyces phages. Genome analyses reveal that these phages are closely related genetically, while experimental approaches show that they have broad overlapping host ranges, infect early in the Streptomyces lifecycle, and induce secondary metabolite production and sporulation in some Streptomyces species. This work expands the group of characterized Streptomyces phages and improves our understanding of Streptomyces phage-host dynamics.


Further thoughts on directional cell movement during morphogenesis.
This essay discusses the directional movements of metazoan tissue cells generally, with special emphasis on neurons, in an attempt to show that the directional movements of all share fundamental similarities.


Role of fluorescein angiography guided laser treatment in aggressive retinopathy of prematurity.
To compare disease regression in cases of Fluorescein Angiography (FA) guided laser vs. conventional laser treatment in infants with Aggressive retinopathy of prematurity (AROP). 60 eyes of 30 infants of AROP were randomized into two groups. In both the group's FA was done once. Montage of the fundus, FA images was created and the vascular area, avascular areas, and skip areas after laser treatment were demarcated and measured. In group 1, FA-guided laser treatment was done whereas in group 2 they were lasered without seeing FA. Infants were followed up every week to look for skip areas and disease regression. The mean vascular retinal area in group 1 and group 2 on fundus images was 302.7 sq. mm and 245.8 sq. mm respectively, while the same on FA was 285.2 sq. mm and 221.3 sq. mm respectively, suggesting overestimation of the vascular area on fundus imaging compared to FA which enabled more objective estimation of avascular loop areas. Retinal skip areas in group 1 and group 2 after 1st laser were 18.7 sq. mm and 73.1 sq. mm respectively (P = 0.001), after 2nd laser was 3.7 sq. mm and 19.2 sq. mm (P = 0.003), which suggests FA-guided laser led to significantly fewer skip areas. Infants had regression in 4.1 ± 0.3 wks and 4.2 ± 0.4 wks in groups 1 and 2, respectively. FA-guided laser ensured lesser skip areas and more complete laser treatment, though regression was similar in both groups.


An instructive role for C. elegans E-cadherin in translating cell contact cues into cortical polarity.
Cell contacts provide spatial cues that polarize early embryos and epithelial cells. The homophilic adhesion protein E-cadherin is required for contact-induced polarity in many cells. However, it is debated whether E-cadherin functions instructively as a spatial cue, or permissively by ensuring adequate adhesion so that cells can sense other contact signals. In Caenorhabditis elegans, contacts polarize early embryonic cells by recruiting the RhoGAP PAC-1 to the adjacent cortex, inducing PAR protein asymmetry. Here we show that the E-cadherin HMR-1, which is dispensable for adhesion, functions together with the α-catenin HMP-1, the p120 catenin JAC-1, and the previously uncharacterized linker PICC-1 (human CCDC85A-C) to bind PAC-1 and recruit it to contacts. Mislocalizing the HMR-1 intracellular domain to contact-free surfaces draws PAC-1 to these sites and depolarizes cells, demonstrating an instructive role for HMR-1 in polarization. Our findings identify an E-cadherin-mediated pathway that translates cell contacts into cortical polarity by directly recruiting a symmetry-breaking factor to the adjacent cortex.


Decoding the Role of Gender in the Relationship Between the Online Payment System and SME Performance: A Case Study Investigating an Emerging Economy-Bangladesh.
This research examines the moderating role of gender on the adoption of online payment systems (OPS). It also explores the impact of using OPS on the performance of SMEs in an emerging economy, using the Technology Acceptance Model (TAM) and Resource-Based View (RBV). The results indicate that male SME owners (entrepreneurs) are more likely to focus on perceived usefulness, whereas female SME entrepreneurs are more likely to focus on perceived ease of use while adopting OPS, according to data obtained from 302 SMEs in Bangladesh through face-to-face surveys. The results also report that the use of OPS has a considerable positive effect on SMEs' performance. The study's findings will add to the scarce research on the impact of using OPS on business performance in the context of SMEs in emerging economies, in addition to enhancing the OPS adoption literature from a gendered lens.


Transportomics for the Characterization of Plant Apocarotenoid Transmembrane Transporters.
Apocarotenoids are carotenoid derivatives produced by the nonenzymatic or enzymatic cleavage of carotenoids, followed by different enzymatic modifications. In plants, apocarotenoids play different roles, such as attraction of pollinators and seeds dispersal, defense against pathogens and herbivores, protection against photo-oxidative stresses, stimulation and inhibition of plant growth and regulation of biological processes in the case of phytohormones abscisic acid and strigolactones. While carotenoids are in general plastid-localized metabolites, apocarotenoids can reach different final destinations inside or outside the cell. The mechanisms of apocarotenoid transport through biological membranes have been poorly studied. This chapter describes a method to characterize transmembrane transporters involved in the transport of polar and amphipathic apocarotenoids. This protocol was successfully used to in vitro characterize the transport activity of ATP-binding cassette (ABC) and multidrug and toxic extrusion (MATE) in microsomes isolated from Saccharomyces cerevisiae expressing these plant transporters.


5-Fluorouracil incorporated into the tissue RNA of human and rat bladder carcinoma after administration of 1-(2-tetrahydrofuryl)-5-fluorouracil combined with uracil.
UFT is an anticancer agent consisting of 1-(2-tetrahydrofuryl)-5-fluorouracil (5-FU) combined with uracil in a molar ratio of 1: 4. Its mechanisms of action are, presumably, inhibition of deoxyribonucleic acid (DNA) synthesis by thymidylate synthetase (TS) and impairment of ribonucleic acid (RNA) function by the incorporation of 5-fluorouridine-5'-triphosphate into RNA. This study was conducted to examine the TS inhibition rate (TS-IR) and the concentration of 5-FU incorporated in RNA per milligram of tissue treated with UFT (F-RNA). We administered UFT to 12 patients with bladder cancer. We also administered UFT to 20 rats bearing bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), and to 10 BBN-untreated control rats. We then determined the total TS concentration, TS-IR, and F-RNA in the human bladder tumor and normal tissues and in the BBN-treated and BBN-untreated rat organs, including the urinary bladder. In the bladder cancer patients, the mean F-RNAs in the bladder tumor and normal tissue were 0.133 +/- 0.137 and 0.056 +/- 0.062 ng/mg, respectively, without a significant difference (P < 0.1). The mean TS-IR was 35.3 +/- 19.6% in the tumor tissue and 38.0 +/- 16.6% in the normal bladder tissue, and this difference was also not significant. In the rat bladder cancer model, the total TS concentration and F-RNA in the tumor after the administration of UFT were 15.32 pmol/g and 0.780 ng/mg, respectively, being markedly higher than the corresponding values (1.22 pmol/g and 0.129 ng/mg) in the control normal bladder tissue. The impairment of RNA metabolism by F-RNA incorporated in RNA did not seem to be the critical mechanism of the antitumor effect of UFT at the usual clinical dose, as neither TS-IR nor F-RNA (as antitumor parameters) seemed to increase significantly after a clinical dose of UFT. However, the inhibition of DNA synthesis and the impairment of RNA were independent mechanisms of the action of high-dose UFT in the experimental rat bladder tumors, as both total is concentration and F-RNA were increased significantly.


Cdc42: new roads to travel.
The roles of Cdc42 in stimulating changes in the actin cytoskeleton and in the establishment of cell polarity have been known for some time. However, evidence implicating Cdc42 in intracellular trafficking and in the regulation of cell growth have continued to surface. Recently, exciting developments have highlighted how Cdc42 might participate in these cellular functions by regulating the processing of the EGF receptor. Here, I discuss these findings within the broader context of how Cdc42 serves as a multifaceted signaling switch that links trafficking events to the control of cell growth.


The psychological, social, and sexual consequences of gestational trophoblastic disease.
Seventy-six women diagnosed with gestational trophoblastic disease (GTD) from 1985 to 1989 completed questionnaires evaluating their status on mood disturbance, marital satisfaction, sexual functioning, psychosocial response to illness, and report of the most stressful event occurring within the past year. Multivariate analyses of variance (MANOVA) were conducted on dependent measures to examine differences between diagnostic groups (partial mole, complete mole, persistent disease), time from diagnosis (less than 1 year, 1-2 years, or 3-5 years from diagnosis), and follow-up status (active disease or remission). MANOVAs revealed no significant differences in the dependent measures based on time from diagnosis, type of medical treatment received, or type of molar disease. The metastatic disease group displayed significantly greater mood disturbance (F(1, 66) = 17.63, P less than 0.0001) and reported suffering clinically significant levels of distress and significantly greater levels of distress in response to the illness (F(33, 39) = 2.32, P less than 0.006). Women with active disease also reported significantly greater levels of distress in response to the illness (F(33, 39) = 2.76, P less than 0.001). Across disease types, GTD patients experience clinically significant levels of anxiety, anger, fatigue, confusion, and sexual problems and are significantly impacted by pregnancy concerns for protracted periods of time.


The effects of electric field assisted composting on ammonia and nitrous oxide emissions varied with different electrolytes.
Enhancing electron transfer through directly elevating electric potential has been verified to reduce gaseous emissions from composting. Reducing electric resistance of composting biomass might be a choice to further strengthening electron transfer. Here, the effects of chemical electrolytes addition on gaseous Nitrogen emission in electric field assistant composting were investigated. Results suggest that adding acidic electrolyte (ferric chloride) significantly reduced ammonia (NH3) emission by 72.1% but increased nitrous oxide (N2O) emission (by 24-fold) (P < 0.05), because of a dual effect on nitrifier activity: i) an elevated abundance and proportion of ammonia oxidizing bacteria Nitrosomonadaceae, and ii) delayed growth of nitrite oxidizing bacteria. Neutral and alkaline electrolytes had no negative or positive effect on N2O or NH3 emission. Hence, there is a potential trade-off between NH3 and N2O mitigation if using ferric chloride as acidic electrolyte, and electrolyte addition should aim to enhance electron production promote N2O mitigation.


Involvement of glutathione peroxidases in the occurrence and development of breast cancers.
Glutathione peroxidases (GPxs) belong to a family of enzymes that is important in organisms; these enzymes promote hydrogen peroxide metabolism and protect cell membrane structure and function from oxidative damage. Based on the establishment and development of the theory of the pathological roles of free radicals, the role of GPxs has gradually attracted researchers' attention, and the involvement of GPxs in the occurrence and development of malignant tumors has been shown. On the other hand, the incidence of breast cancer in increasing, and breast cancer has become the leading cause of cancer-related death in females worldwide; breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. Therefore, this article focused on the molecular mechanism and function of GPxs in the occurrence and development of breast cancer to understand their role in breast cancer and to provide a new theoretical basis for the treatment of breast cancer.


Crystal structure of erioflorin isolated from Podanthus mitiqui (L.).
The title compound, erioflorin, C19H24O6 [systematic name: (1aR,3S,4Z,5aR,8aR,9R,10aR)-1a,2,3,5a,7,8,8a,9,10,10a-deca-hydro-3-hy-droxy-4,10a-dimethyl-8-methyl-idene-7-oxooxireno[5,6]cyclo-deca-[1,2-b]furan-9-yl methacrylate], is a tricyclic germacrane sesquiterpene lactone, which was isolated from Podanthus mitiqui (L.). The compound crystallizes in the space group P212121, and its mol-ecular structure consists of a methacrylic ester of a ten-membered ring sesquiterpenoid annelated with an epoxide and a butyrolactone. The structure is stabilized by one intramolecular C-H⋯O hydrogen bond. An O-H⋯O hydrogen bond and further C-H⋯O interactions can be observed in the packing.


Mechanisms of localization of gallium-67 in tumors.
The mechanism of tumor localization of gallium-67 (67Ga) is not known with certainty, although much information has been derived regarding the biodistribution and subcellular fate of 67Ga in a variety of tumors and other tissues from experimental animals. After intravenous administration, 67Ga is bound to transferrin in the blood, and distributed to liver, lacrimal glands, salivary glands, and soft tissue tumors. Within the cells of the liver and tumors, gallium is found in lysosomes, and rough endoplasmic reticulum. Within these organelles, 67Ga is bound to a variety of macromolecules, including transferrin, ferritin, and a 45,000 molecular weight glycoprotein. Recent studies of tumor cells growing in tissue culture suggest an important role for transferrin in 67Ga tumor uptake. This uptake is mediated by a transferrin specific cellular receptor.


Contextualizing critical care family needs through triangulation: an Australian study.
Family needs and concerns within the critical care context have been thoroughly explored from the quantitative perspective utilizing the Critical Care Family Needs Inventory (CCFNI). Nursing interventions have been designed on the basis of the findings from these studies. However, while the CCFNI would seem to encompass all the possible needs of families with a critically ill loved one, at no time were the family members themselves consulted at length in regard to the development of the instrument, or in any subsequent validation studies. Individual reality generates the variables that are measured in a needs analysis, and the family member experiences encompass dimensions that are not easily assessed by quantification. In fact the unique experiences of family members underpin their perception of need. Methodological triangulation formed the basis for this study to determine the degree of confirmation (or otherwise) between family member respondents to the CCFNI (n = 105) and those participating in an interview (n = 26) designed to explore needs and experiences. The qualitative data served the purpose of completeness by providing a more contextual representation of needs and therefore greater depth of understanding of the whole construct. The results indicate that, while there were many areas of convergence between the two samples, there were also areas of diveregence. Two major needs emerged from the interviews that are not represented on the CCFNI: the need of family members to provide reassurance and support to the patient; and their need to protect (others as well as the patient). A more complete understanding of family needs was obtained through the contextualization of their experiences.


Diagnosis of fetal alcohol syndrome (FAS): German guideline version 2013.
Fetal alcohol syndrome (FAS) belongs to the umbrella of fetal alcohol spectrum disorders (FASD) and affects 0.02-0.8% of all annual births with a high number of undetected cases. FAS has severe and life determining consequences for the affected individual and his family. The aim of the German guideline version 2013 is to provide objectively evaluated, evidence-based, clinically relevant and easily applicable diagnostic criteria for the full picture FAS. A systematic literature review (2001-2011), analysis of international guidelines and focused hand search were performed. Based on the evidence-assessed literature the multidisciplinary guideline group (14 German Professional Societies, the patient support group "FASD Germany" and 15 additional experts) consented recommendations for the diagnosis of FAS. The following diagnostic criteria for FAS resulted: at least one deficit of growth, three defined facial characteristics and one functional or structural anomaly of the central nervous system. Confirmation of intrauterine alcohol exposure is not considered as a prerequisite for FAS diagnosis. The German guideline presented here constitutes an unbiased evidence-based approach to the diagnosis of patients with fetal alcohol syndrome. It includes a practical pocket guide FAS for a quick overview of the diagnostic workup in everyday clinical work.


A dual-signal fluorometric-colorimetric sensing platform and visual detection with a smartphone for the determination of β-galactosidase activity based on fluorescence silicon nanoparticles.
As one of primary biomarkers of ovarian cancer in early stages, β-galactosidase (β-Gal) is significant in the discovery and diagnosis of the disease. In this work, we constructed a multi-signal sensing platform based on silicon nanoparticles (Si NPs) for β-Gal activity determination. When β-Gal was introduced to the sensing system, 2-Nitrophenyl β-D-galactopyranoside (ONPG) could be converted to o-Nitrophenol (o-NP), which had a characteristic absorption peak at 416 nm and the colorless solution turned yellow. The fluorescence emission of Si NPs at 450 nm can be greatly quenched by o-NP as a consequence of inner filter effect (IFE). This dual-signal fluorometric and colorimetric determination approach could be utilized to detect β-Gal in the range of 2-120 U/L and 6-120 U/L. The limits of detection were 1.36 U/L and 1.07 U/L, respectively. This sensing platform could be successfully utilized to detect β-Gal in real samples. Additionally, a visual detection method was designed to achieve quantitative analysis of β-Gal with the assistance of the smartphone.


Plasma copeptin and long-term outcomes in acute ischemic stroke.
The identification of patients at highest risk for adverse outcome who are presenting with acute ischemic stroke to the emergency department remains a challenge. This study firstly investigates the long-term prognostic value of the stress marker copeptin in Chinese patients with acute ischemic stroke. In a prospective study, copeptin levels were measured using a new sandwich immunoassay on admission in plasma of 245 consecutive patients with an acute ischemic stroke. The prognostic value of copeptin to predict the functional outcome and mortality within one year was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Patients with an unfavorable outcomes and non-survivors had significantly increased copeptin levels on admission (P < 0.0001 and P < 0.0001). Multivariate Cox regression analysis adjusted for common risk factors showed that copeptin was an independent predictor of functional outcome (hazard ratio = 3.88; 95% CI: 1.94-7.77) and non-survivors (hazard ratio = 5.99; 95% CI: 2.55-14.07). The area under the receiver operating characteristic curve of copeptin was 0.75 (95% CI, 0.70-0.82) for functional outcome and 0.867 (95% CI, 0.802-0.933) for mortality. Copeptin levels are a novel and complementary biomarker to predict functional outcome and mortality 1 year after acute ischemic stroke.


Tissue factor links inflammation, thrombosis, and senescence in COVID-19.
COVID-19 is a highly contagious respiratory infection caused by the SARS-CoV-2 virus. The infected lung epithelial cells secrete a group of chemokines and cytokines, which triggers harmful cytokine storms and hyper-thrombotic responses. Recent studies have proposed that viral-induced senescence is responsible for cytokine release and inflammation in COVID-19 patients. However, it is unknown whether cellular senescence is commonly triggered after viral infection and how inflammation and thrombosis, hyper-activated in these patients, are functionally connected. To address these questions, we conducted a bioinformatics-based meta-analysis using single-cell and bulk RNA sequencing datasets obtained from human patient studies, animal models, and cell lines infected with SARS-CoV-2 and other respiratory viruses. We found that the senescence phenotype is robustly upregulated in most SARS-CoV-2-infected patients, especially in the infected lung epithelial cells. Notably, the upregulation of Tissue factor (F3), a key initiator of the extrinsic blood coagulation pathway, occurs concurrently with the upregulation of the senescence-associated secretory phenotype (SASP) factors. Furthermore, F3 levels are positively correlated with the senescence and hyper-coagulation gene signatures in COVID-19 patients. Together, these data demonstrate the prevalence of senescence in respiratory viral infection and suggest F3 as a critical link between inflammation, thrombosis, and senescence in these disease states.


RhoA signaling in phorbol ester-induced apoptosis.
Exposure of cells to phorbol ester activates protein kinase C (PKC) to induce apoptosis or differentiation, depending on the cellular context. In erythroblastic cell lines, TF-1 and D2, upregulation of the RhoA signaling promotes phorbol ester-induced apoptosis through activating Rho-associated kinase (ROCK)/phosphorylation of myosin light chain (MLC), thus generating membrane contraction force. As a result, cell adhesion is inhibited and death receptor-mediated death pathway is activated in these cells with a concurrent changes in nucleocytoplasmic signaling for protein trafficking. A microtubule-regulated GEF-H1, which is a specific RhoA activator, was identified to contribute to RhoA activation in these cells. Thus, a cytoskeleton-regulated RhoA signaling cooperates with PKC activation constitutes a cellular context to determine the cell fate in response to phorbol ester stimulation.


Cold-evoked potentials - Ready for clinical use?
Cold-evoked potentials (CEPs) are known to assess the integrity of A-delta fibres and the spinothalamic tract. Nevertheless, the clinical value was not investigated previously. The aim of this study was to measure CEPs in 16 healthy subjects from the face, hand and foot sole and to investigate whether CEPs reliably detect A-delta fibre abnormalities. Swift cold stimuli were applied to the skin with a commercially available thermode, which cooled down from 30 to 25 °C in approximately 0.5 s. CEP latencies (N1, N2 and P2) and amplitudes (N1, N2/P2) were recorded with EEG. Reversible A-fibre function loss was induced by applying a selective A-fibre block at the superficial radial nerve. In all 16 subjects CEPs could be recorded from all locations; N2, P2 mean latencies were 276.4 ± 38.9 and 389.8 ± 52.5 (face), 318.6 ± 31.6 ms and 477.7 ± 43.6 (hand), and 627.6 ± 84.4 and 774.2 ± 94.0 (foot sole). N2/P2 amplitudes were 10.7 ± 4.1, 11.3 ± 4.1 and 7.5 ± 4.1 μV. During A-fibre block no CEPs were detectable in the grand average, which restored 10 min after block removal. CEPs were reliably recorded in healthy subjects at the hand, face and foot. Experimentally induced reversible A-delta fibre function loss was detected by CEPs. Functional recovery was assessed as well. This study is basis for further CEP evaluation studies and might be the first step for implementing CEPs in clinical routine for the early diagnosis of small-fibre disease. WHAT DOES THIS STUDY ADD?: Cold-evoked potentials are capable of reliably measuring A-delta fibre integrity, loss of function and functional recovery in healthy subjects, which is an essential prerequisite for diagnostic use in patients with small-fibre disease.


Purification of anti-MUC1 antibodies by peptide mimotope affinity chromatography using peptides derived from a polyvalent phage display library.
A polyvalent, lytic phage display system (T7Select415-1b) displaying a random peptide library has been investigated for its ability to discover novel mimotopes reactive with the therapeutic monoclonal antibody C595. Sequence analysis of enriched phage lead to the identification of a predominant sequence RNREAPRGKICS, and two other consensus sequences RXXP and RXP. The novel synthetic peptide RNREAPRGKICS was linked to beaded agarose and the performance as a mimotope affinity chromatography matrix evaluated. Antibody purified using the novel matrix was found to be of higher specific reactivity than antibody purified using the conventional epitope matrix (peptide APDTRPAPG). The RNREAPRGKICS peptide binding to C595 demonstrated a higher equilibrium association constant (K(A)=0.75 x 10(6)) than the epitope peptide (K(A)=0.16 x 10(6)). Circular dichroism showed that the novel peptide had a more highly ordered structure at 4 degrees C and room temperature, than the epitope peptide.


Diabetes distress and peripheral neuropathy are associated with medication non-adherence in individuals with type 2 diabetes in primary care.
Psychosocial factors like diabetes distress and social support, as well as the presence of complications, affect an individual's self-management ability; however, their role in adherence behaviours is not yet clear. We examined the role of psychosocial factors and complications in non-adherence behaviours in individuals with diabetes in primary care. Baseline survey with nine-month follow up through medical records of patients with type 2 diabetes attending primary care. Medication adherence and diabetes distress were assessed using Morisky Green Levine Medication Adherence Scale and Problem Areas in Diabetes, respectively. Appointment adherence was assessed through medical records. Of the 448 participants studied, 59.8% had medication non-adherence and 21.7% were non-adherent to scheduled appointments. PAID score (odds ratio (OR) 1.01, 95% confidence interval 1.00-1.03, p = 0.013), peripheral neuropathy (OR 1.99, 95%CI 1.18-3.37, p = 0.01), home glucose monitoring (OR 0.46, 95%CI 0.30-0.69, p < 0.001), HbA1c (OR 1.34, 95%CI 1.13-1.61, p = 0.001), and age (OR 0.96, 95%CI 0.93-0.98, p = 0.001) were associated with medication non-adherence. Indian ethnicity (OR 2.93, 95%CI 1.59-5.39, p = 0.001), secondary or higher education (OR 1.94, 95%CI 1.14-3.27, p = 0.014), and HbA1c (OR 1.38, 95%CI 1.18-1.63, p < 0.001) were associated with appointment non-adherence. Non-adherence behaviours were prevalent and significantly associated with higher HbA1c. Medication non-adherence was more likely in younger individuals, those with higher diabetes distress or peripheral neuropathy. Appointment non-adherence was more likely in individuals of Indian ethnicity or those with higher education. Greater support for these groups may help improve adherence behaviours and outcomes.


Morbidity and mortality of coronary bypass grafting in patients 70 years of age and older.
The hospital mortality and major factors contributing to hospital morbidity and postoperative length of stay were examined in 597 consecutive patients 70 years of age and older who underwent isolated coronary artery bypass grafting (CABG) between January, 1978, and December, 1983. The mean age of the patients was 73 years, and 66% were men. Unstable angina was present in 59% of patients, left main coronary disease in 13%, and moderate or severe left ventricular dysfunction in 10%. The mean number of arteries grafted per patient was 3.4. The hospital mortality was 2.7% (16 patients) and was higher than the mortality among 4,125 patients less than 70 years of age (0.4% in 18 patients) operated on during the same interval (p less than 0.001). In multivariate regression analyses, age of 80 years or greater, evolving myocardial infarction, serious coexisting illness, major left ventricular dysfunction, emergent operation, and the development of major postoperative complications were significant (p less than 0.05) independent predictors of increased hospital mortality. Major complications occurred in 135 patients (23%). In multivariate analyses, the presence of vascular disease, serious concomitant illness, and the need for urgent or emergent operation were significant independent predictors of the development of major postoperative complications. The mean duration of postoperative hospital stay was 10.6 +/- 6 (standard deviation) days. In multivariate analyses, the development of major postoperative complications was the only variable independently predictive of prolonged hospital stay. With current techniques, CABG procedures can be safely performed in the elderly with mortality and morbidity rates only slightly higher than those in younger patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Simultaneous measurement of basal pancreatic, gastric acid secretion, plasma gastrin, and secretin during smoking.
The effect of smoking one unfiltered cigarette every 15 min for 1 hr on basal gastric acid and pancreatic secretion was studied in 10 subjects with a history of duodenal ulcer and 10 without duodenal ulcer. Smoking induced a transient rise of basal acid output followed by a slight decrease. This effect was more pronounced in the duodenal ulcer group. Smoking markedly inhibited fluid and bicarbonate secretion during the smoking period. The bicarbonate and fluid secretion returned to control levels within 30 to 60 min in the ulcer group and in 60 to 90 min in the nonulcer group. There was no difference in the degree of inhibition of pancreatic secretion between the two groups. Immunoreactive gastrin and secretin in the peripheral venous blood did not change significantly during smoking. The degree of inhibition of basal pancreatic secretion correlated well with the plasma concentrations of nicotine. These observations indicate that smoking in the fasting state induces alterations of basal gastric and pancreatic secretions which are not related to changes in plasma gastrin and secretin concentration, but to plasma concentrations of nicotine. The implication of this study in relation to a possible causal association between cigarette smoking and peptic ulcer disease is discussed.


Efficacy and safety of different PD-1 inhibitors in combination with lenvatinib in the treatment of unresectable primary liver cancer: a multicentre retrospective study.
Immune checkpoint inhibitors (ICIs) are safe and efficacious treatments for advanced primary liver cancer (PLC). The efficacy of different ICIs in the treatment of liver cancer remains unclear. The purpose of this study was to explore whether there is a difference in the efficacy and safety of various programmed cell death protein 1 (PD-1) inhibitors in combination with lenvatinib in the treatment of unresectable PLC. Patients with PLC treated with lenvatinib in combination with PD-1 inhibitors (camrelizumab, tislelizumab, sintilimab, or pembrolizumab) between January 2018 and December 2021 were retrospectively enrolled. Tumor response, adverse events, and grades were evaluated. Kaplan-Meier analysis and log-rank test were used to compare the overall survival and progression-free survival of patients treated with different PD-1 inhibitors. Cox regression analysis was used for univariate and multivariate analyses to identify clinical variables related to treatment efficacy. This study included a total of 176 patients who received a combination of lenvatinib and PD-1 inhibitors. Of these, 103 patients received camrelizumab, 44 received tislelizumab, 20 received sintilimab, and 9 received pembrolizumab. There was no significant difference in the pairwise comparison of camrelizumab, tislelizumab, sintilimab, and pembrolizumab using Kaplan-Meier survival analysis. Adverse events occurred in 40 (22.7%) patients (grade ≥ 3, 2.3%). The incidence of grade 3 adverse events among the four PD-1 inhibitor groups was below 5%. Camrelizumab, tislelizumab, sintilimab, and pembrolizumab are viable options for patients with unresectable PLC. These PD-1 inhibitors in combination with lenvatinib showed good safety profiles. The results guide selecting treatment for patients with unresectable PLC.


Phonological performance measured by speech severity indices compared with correlated factors.
Some factors seem to influence speech impairment among phonologically disordered children. The aim was to compare severity indices with some correlated factors. Observational, analytical and cross-sectional study conducted within the Language-Speech-Hearing Sciences Course, Universidade de São Paulo. Fifty phonologically disordered children with ages ranging from 4 to 11 years took part. The indices were calculated from phonology tests and were correlated with anamnesis and audiological data. Students t test and Spearmans correlation were used to compare percentages of consonants correct (PCC) and process density index (PDI) for children with and without otitis, upper respiratory histories and audiological abnormalities, with regard to whether or not they were comprehended during assessment, their ages when they started to speak and their ages at the assessment. The higher the age at the assessment was, the higher the PCC (imitation: 0.468; naming: 0.431; Spearmans correlation) and the lower the PDI (imitation: 0.459; naming: 0.431); the later the child started to speak, the lower the PCC (imitation p = 0.064; naming p = 0.050) and the higher the PDI (imitation p = 0.067; naming p = 0.042). There were differences between groups with and without upper respiratory history (PCC: imitation p = 0.016, naming p = 0.005; PDI: imitation p = 0.014, naming p = 0.008). There was no difference between the groups regarding otitis, comprehension during the assessment and audiological data. Children with upper respiratory histories who began to speak later presented more severe speech impairment indices.


Dupuytren's Contracture: The Readability of Online Information.
Dupuytren's contracture is a common hand pathology for which consultation and treatment are largely at the patient's discretion. The objective of this study was to evaluate the readability of current online patient information regarding Dupuytren's contracture. The largest public search engines (Google, Yahoo, and Bing) were queried using the search terms "Dupuytren's contracture," "Dupuytren's disease," "Viking's disease," and "bent finger." The first 30 unique websites by each search were analyzed and readability assessed using five established algorithms: Flesch Reading Ease, Gunning-Fog Index, Flesch-Kincaid Grade level, Coleman-Liau index, and Simple Measure of Gobbledygook grade level. Analysis of 73 websites demonstrated an average Flesch Reading Ease score of 48.6 ± 8.0, which corresponds to college reading level. The readability of websites ranged from 10.5 to 13.3 reading grade level. No article was written at or below the recommended sixth grade reading level. Information on the internet on Dupuytren's contracture is written at higher than recommended reading grade level. There is a need for high-quality patient information on Dupuytren's contracture at appropriate reading grade levels for patients of various health literacy backgrounds. Hospitals, universities, and academic organizations focused on the development of readable online information should consider patients' input and preferences.


Leiomyosarcomas of the oral tissues: clinicopathologic analysis of 50 cases.
Primary oral leiomyosarcomas are rare tumors. Information regarding the biological behavior, prognosis, and appropriate management of this neoplasm is lacking in the literature. The purpose of this report was to summarize the data of isolated case reports of primary oral leiomyosarcoma that have been published in the English literature during the past 25 years. The cases of 4 additional new patients who have been treated in our department during the past 10 years are also presented. The data for 46 patients obtained from 32 individual articles retrieved from the English literature were added to our 4 cases and produced a total number of 50 cases of primary leiomyosarcomas of the oral tissues. Patients were analyzed according to demographic data, anatomic location, type of treatment, and survival. Primary oral leiomyosarcoma may affect any age with peaks of occurrence in the third, sixth, and seventh decades of life. There is no gender predilection. Female patients presented the higher incidence in the third decade, whereas males had an even age distribution. The tumor arises in approximately 70% of the cases in the maxillary and mandibular bones. Radical surgery was the treatment of choice. Radiotherapy and chemotherapy when applied in recurrent tumors had little effect. The most adverse prognostic factor was the positive surgical margins. The 5-year survival was 62% (62.9% for females and 52.6% for males, P > .1968). Cases of oral leiomyosarcoma appear to be associated with major neurovascular structures of the facial skeleton, as evidenced from the imaging studies of our 4 patients. Primary oral leiomyosarcoma is a rare tumor that should be managed with aggressive surgical resection in order to safeguard curability. Histopathologic diagnosis is greatly facilitated with positive immunohistochemical staining for smooth muscle antigenic markers.


Severe Staffing And Personal Protective Equipment Shortages Faced By Nursing Homes During The COVID-19 Pandemic.
The coronavirus disease 2019 (COVID-19) pandemic continues to devastate US nursing homes. Adequate personal protective equipment (PPE) and staffing levels are critical to protect nursing home residents and staff. Despite the importance of these basic measures, few national data are available concerning the state of nursing homes with respect to these resources. This article presents results from a new national database containing data from 98 percent of US nursing homes. We find that more than one in five nursing homes reports a severe shortage of PPE and any shortage of staff. Rates of both staff and PPE shortages did not meaningfully improve from May to July 2020. Facilities with COVID-19 cases among residents and staff, as well as those serving more Medicaid recipients and those with lower quality scores, were more likely to report shortages. Policies aimed at providing resources to obtain additional direct care staff and PPE for these vulnerable nursing homes, particularly in areas with rising community COVID-19 case rates, are needed to reduce the national COVID-19 death toll.


Childhood cicatricial pemphigoid with exclusive gingival involvement.
A case of cicatricial pemphigoid in a 13-year-old boy presenting in the form of desquamative gingivitis is described. There are only 7 documented cases of childhood cicatricial pemphigoid reported in the literature.


Lumbocostovertebral syndrome with associated VACTERL anomaly.
Lumbocostovertebral syndrome is a rare clinical association syndrome rarely accompanied by associated VACTERL anomalies. Only one similar case has been reported previously. We describe the second case, where a male neonate born at 38 weeks of gestation had an unusually high number of congenital anomalies including thoracic hemivertebrae with kyphoscoliosis, a high anorectal malformation, dextrocardia with an atrial septal defect, renal pelvic pyelectasis, hypospadias, and congenital talipes equinovarus.


Dynamics and cooperativity of Trp-cage folding.
In this study, multiple independent molecular dynamics (MD) simulations on Trp-cage folding were performed at 300, 325 and 375 K using generalized Born (GB) implicit solvent model. The orientational movement of the side-chain of Trp6 to form a hydrophobic core with 3(10)-helix was observed. The breaking/formation of a salt bridge between Asp9 and Arg16 was proposed to be the prerequisite for Trp-cage folding/refolding. Our results demonstrate that the cooperation between the salt bridge and the Trp6 orientation leads to a stable tertiary structure of Trp-cage. Analyses on backbone concerted motions at different temperatures indicate that interactions between Trp6 and 3(10)-helix & Pro18 and between Pro12 and Pro17 & Pro18 are weakened at 375 K but strengthened at lower temperatures, suggesting that they could be the potential driving force of hydrophobic collapse.


[Collection, evaluation and utilization of local varieties of Fritillaria thunbergii Miq].
Nine local varieties of Fritillaria thunbergii were collected and their plant morphology, phenology, disease resistance yield characters and breeding rate were studied. A new and better variety (Duozhi) was found and put to use.


Thermodynamics of solutions. II. Flurbiprofen and diflunisal as models for studying solvation of drug substances.
Three independent methods (sublimation, solubility and solution calorimetry) were used to study the dissolution and solvation processes of diflunisal (DIF) and flurbiprofen (FBP). Thermodynamic functions for the sublimation of DIF and FBP were obtained. Concentrations of saturated solutions and standard solution enthalpies of DIF and FBP in aliphatic alcohols and individual organic solvents were measured. Correlation analysis between: (a) the thermodynamic functions for a substance in various solvents, and (b) the same functions for different compounds was carried out. The investigated substances can be arranged with increasing Gibbs energy of solvation as follows: benzoic acid<DIF<FBP. Enthalpy is found to be the major driving force of the solvation process for all the studied compounds. The ratio of specific and nonspecific solute-solvent interaction in terms of enthalpies (epsilon (H)) and in terms of entropies (epsilon (S)) was analyzed. Based on the experimental data, a compensation effect of thermodynamic solubility functions of the investigated substances both in alcohols and in organic solvents was found.


An extensive dataset of handwritten central Kurdish isolated characters.
To collect the handwritten format of separate Kurdish characters, each character has been printed on a grid of 14 × 9 of A4 paper. Each paper is filled with only one printed character so that the volunteers know what character should be written in each paper. Then each paper has been scanned, spliced, and cropped with a macro in photoshop to make sure the same process is applied for all characters. The grids of the characters have been filled mainly by volunteers of students from multiple universities in Erbil.


Pressure pulse contour-derived stroke volume and cardiac output in the morbidly obese patient.
The pressure pulse contour method for measuring stroke volume (SV) and cardiac output (CO) has come of age. Various methods have been proposed, but at this time no single technique has shown clear superiority over the others. This commentary and review discusses the various methods, and particularly the pressure recording analytical method (PRAM). Dissection of the method shows that vascular wall abnormalities, which are not unique to the morbidly obese state, represent one more biophysical perturbation causing inaccuracy in stroke volume and cardiac output determination. As PRAM is an uncalibrated method, its accuracy depends on certain assumptions that may not fully explain the multitude of combinations and permutations that define pulsatile blood flow; specifically, the area under the pressure curve during systole and the morphologic characteristics of the waveform throughout the cardiac cycle. As a result of incomplete theory, referenced specifically to the morbidly obese individual, PRAM does not faithfully mimic established reference standards of flow; it systematically underestimates stroke volume and cardiac output. Field equations, that is, equations that are applicable over the full gamut of hemodynamic conditions and vascular pathology, are analytically derived truisms. They require input variables that satisfy the natural state of affairs. To realize this state of absolute biophysical bliss, these variables should ideally be measured. Unfortunately, because of the constraints of practicality, shortcuts to the absolute truth are obligatorily required. As a result, pressure pulse contour methods have evolved that employ curve analysis and neural networking techniques, providing uncalibrated facsimiles of SV and CO.