Clinical significance of renal changes engendered by aminoglycosides in man.
Aminoglycoside antibiotics are associated with decreasing renal function of sufficient magnitude to influence adversely the management of approximately 10% of cases. Onset usually occurs after one week's treatment, but may be delayed until after the drugs are discontinued. Renal insufficiency is generally transient, mild, non-oliguric, and is characterized by recovery. There is currently no clear evidence that aminoglycosides cause permanent or subsequent progressive renal damage. Although age, pre-existing renal dysfunction, volume depletion, prior exposure to other nephrotoxic drugs and total drug dose have been suggested as host variables on the basis of animal studies, human studies have not shown predictive factors of toxicity. Peak and valley serum concentrations are more likely to reflect renal function than to predict toxicity. Studies in man are dogged by confounding variables characteristic of the critically ill. Comparative trials of toxicity have required the enrolment of large numbers of patients to show statistical differences which may have little clinical significance. Thus the choice of aminoglycoside should not be governed by nephrological criteria.


Suppressive Effects of Tea Catechins on Breast Cancer.
Tea leaf (Camellia sinensis) is rich in catechins, which endow tea with various health benefits. There are more than ten catechin compounds in tea, among which epigallocatechingallate (EGCG) is the most abundant. Epidemiological studies on the association between tea consumption and the risk of breast cancer were summarized, and the inhibitory effects of tea catechins on breast cancer, with EGCG as a representative compound, were reviewed in the present paper. The controversial results regarding the role of tea in breast cancer and areas for further study were discussed.


Organizational readiness to change as a leverage point for improving safety: a national nursing home survey.
A stronger safety climate in nursing homes may reduce avoidable adverse events. Yet efforts to strengthen safety climate may fail if nursing homes are not ready to change. To inform improvement efforts, we examined the link between organizational readiness to change and safety climate. Seven safety climate domains and organizational readiness to change were measured with validated Community Living Center/CLC Employee Survey of Attitudes about Resident Safety and Organizational Readiness to Change Assessment. Safety climate domains comprised of safety priorities, supervisor commitment to safety, senior management commitment to safety, safety attitudes, environmental safety, coworker interactions around safety, and global rating of CLC. We specified models with and without readiness to change to explain CLC- and person-level variance in safety climate domains. One thousand three hundred ninety seven workers (frontline staff and managers) responded from 56 US Veterans Health Administration CLCs located throughout the US. Adding readiness to change reduced baseline CLC-level variance of outcomes (2.3-9.3%) by > 70% for interpersonal domains (co-workers, supervisors, and senior management). Readiness to change explained person-level variance of every safety climate domain (P < 0.05), especially for interpersonal domains. Organizational readiness to change predicted safety climate. Safety climate initiatives that address readiness to change among frontline staff and managers may be more likely to succeed and eventually increase resident safety.


Oxygen and vacancy defects in silicon. A quantum mechanical characterization through the IR and Raman spectra.
The Infrared (IR) and Raman spectra of various defects in silicon, containing both oxygen atoms (in the interstitial position, Oi) and a vacancy, are computed at the quantum mechanical level by using a periodic supercell approach based on a hybrid functional (B3LYP), an all-electron Gaussian-type basis set, and the Crystal code. The first of these defects is VO: the oxygen atom, twofold coordinated, saturates the unpaired electrons of two of the four carbon atoms on first neighbors of the vacancy. The two remaining unpaired electrons on the first neighbors of the vacancy can combine to give a triplet (Sz = 1) or a singlet (Sz = 0) state; both states are investigated for the neutral form of the defect, together with the doublet solution, the ground state of the negatively charged defect. Defects containing two, three, and four oxygen atoms, in conjunction with the vacancy V, are also investigated as reported in many experimental papers: VO2 and VOOi (two oxygen atoms inside the vacancy, or one in the vacancy and one in interstitial position between two Si atoms) and VO2Oi and VO22Oi (containing three and four oxygen atoms). This study integrates and complements a recent investigation referring to Oi defects [Gentile et al., J. Chem. Phys. 152, 054502 (2020)]. A general good agreement is observed between the simulated IR spectra and experimental observations referring to VOx (x = 1-4) defects.


Multicenter, randomized, open-label Phase II study comparing S-1 alternate-day oral therapy with the standard daily regimen as a first-line treatment in patients with unresectable advanced pancreatic cancer.
Non-inferiority for overall survival (OS) following alternate-day treatment with the oral anticancer drug S-1 compared with standard daily treatment was assessed in Japanese patients with unresectable advanced pancreatic cancer in a multicenter, randomized, phase II study. This trial was registered at the UMIN Clinical Trials Registry (no. 000008604). Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned 2:1 to treatment with alternate-day (twice daily on alternate days from days 1 through 42 of a 42-day cycle) or daily (twice daily on days 1 through 28 of a 42-day cycle) treatment with S-1. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), time to treatment failure, response rate, quality of life assessments, and safety. A total of 190 patients were enrolled, of which 185 were included in the final analysis (alternate-day: 121; daily: 64). Median OS was 9.4 for the alternate-day group and 10.4 months for the daily group [hazard ratio (HR), 1.19; 95% credible interval, 0.86 to 1.64], indicating that non-inferiority of alternate-day treatment to daily treatment was not demonstrated. Median PFS was 3.0 for the alternate-day group and 4.2 months for the daily group (HR, 1.65; 95% credible interval, 1.20-2.29). The incidence of anorexia, fatigue, neutrophils, pigmentation, and pneumonitis was lower in alternate-day treatment compared with daily treatment. S-1 for advanced pancreatic cancer should be taken daily as recommended, based on the decreased OS and PFS and marginal improvement in safety observed in the alternate-day group.


The vestibular system: Contributions of Lorente de Nó.
Rafael Lorente de Nó was a neuroscientist that worked alongside two of the giants of Medicine, the Nobel Prize winners Cajal and Bárány. To describe the contributions of Lorente de Nó to vestibular neuroscience. Detailed review of the publications of Lorente de Nó and analysis of the archives from Junta para Ampliación de Estudios e Investigaciones Científicas at Residencia de Estudiantes (Madrid, Spain), Casa de Salud Valdecilla at Hospital Universitario Marqués de Valdecilla (Santander, Spain), Becker Medical Library at Washington University (St. Louis, MO, USA), Rockefeller Archive Center (Sleepy Hollow, New York, NY, USA), Archivo Fernando de Castro (Madrid, Spain), Biblioteca Nacional de España (Madrid, Spain) and Legado Cajal at Instituto Cajal (Madrid, Spain). Most of this material is unpublished and includes over a hundred letters to or from Lorente. Lorente de Nó made a substantial contribution to our understanding of the vestibular system. Amongst these, he meticulously detailed the course of the vestibular nerve and its central projections. He described the vestibulo-ocular reflex as the consequence of an integration of the various nuclei and connections across the vestibular system, rather than a simple three-neuron arc. He also highlighted the role of the reticular formation in the generation of the fast phase of the nystagmus. Lorente de Nó was a pioneer of modern neuro-otology, having made outstanding contributions to vestibular neuroscience, forging novel discoveries that still burn true today.


Fast and Reversibly Humidity-Responsive Fluorescence Based on AIEgen Proton Transfer.
The construction of humidity-responsive fluorescent materials with reversibility, specificity, and sensitivity is of great importance for the development of information encryption, fluorescence patterning, and sensors. Nevertheless, to date, the application of these materials has been limited by their slow response rate and nonspecificity. Herein, a humidity-responsive fluorescence system was designed and assembled to achieve a rapid, reversible, and specific moisture response. The system comprised tetra-(4-pyridylphenyl)ethylene (TPE-4Py) as a fluorescent proton acceptor with an aggregation-induced emission (AIE) effect and poly(acrylic acid) (PAA) as a proton donor with an efficient moisture-capturing ability. The fluorescence color and intensity rapidly changed with increasing relative humidity (RH) because of TPE-4Py protonation, and TPE-4Py deprotonation resulted in recovery of the original fluorescence color in low-humidity environments. The proton transfer between the pyridyl group in TPE-4Py and the carboxyl group in PAA was reversible and chemically stable, and the humidity-responsive fluorescence system showed a high response/recovery speed, an obvious color change, good reversibility, and an outstanding specific moisture response. Because of these advantages, diverse applications of this humidity-responsive fluorescence system in transient fluorescent patterning and the encryption of information were also developed and demonstrated.


Effects of arch height of the foot on angular motion of the lower extremities in running.
It has been suggested that a relationship exists between the height of the medial longitudinal arch of the foot and athletic injuries to the lower extremities. However, the functional significance of arch height in relation to injury is not well understood. The purpose of this study was to determine the influence of arch height on kinematic variables of the lower extremities that have been associated with the incidence of injury in running in an attempt to gain some insight into a functional relationship between arch height and injury. The three-dimensional kinematics of the lower extremities were measured during running for 30 subjects using high-speed video cameras. A joint coordinate system was used to calculate the three-dimensional orientation of the ankle joint complex for a single stance phase. Simple, linear regression analyses showed that arch height does not influence either maximal eversion movement or maximal internal leg rotation during running stance. However, assuming that knee pain in running can result from the transfer of foot eversion to internal rotation of the tibia, a functional relationship between arch height and injury may exist in that the transfer of foot eversion to internal leg rotation was found to increase significantly with increasing arch height. A substantial (27%), yet incomplete, amount of the variation in the transfer of movement between subjects was explained by arch height, indicating that there must be factors other than arch height that influence the kinematic coupling at the ankle joint complex. Additionally, the transfer of movement is only one factor of many associated with the etiology of knee pain in running.(ABSTRACT TRUNCATED AT 250 WORDS)


Embedding objects during 3D printing to add new functionalities.
A novel method for integrating and embedding objects to add new functionalities during 3D printing based on fused deposition modeling (FDM) (also known as fused filament fabrication or molten polymer deposition) is presented. Unlike typical 3D printing, FDM-based 3D printing could allow objects to be integrated and embedded during 3D printing and the FDM-based 3D printed devices do not typically require any post-processing and finishing. Thus, various fluidic devices with integrated glass cover slips or polystyrene films with and without an embedded porous membrane, and optical devices with embedded Corning(®) Fibrance™ Light-Diffusing Fiber were 3D printed to demonstrate the versatility of the FDM-based 3D printing and embedding method. Fluid perfusion flow experiments with a blue colored food dye solution were used to visually confirm fluid flow and/or fluid perfusion through the embedded porous membrane in the 3D printed fluidic devices. Similar to typical 3D printed devices, FDM-based 3D printed devices are translucent at best unless post-polishing is performed and optical transparency is highly desirable in any fluidic devices; integrated glass cover slips or polystyrene films would provide a perfect optical transparent window for observation and visualization. In addition, they also provide a compatible flat smooth surface for biological or biomolecular applications. The 3D printed fluidic devices with an embedded porous membrane are applicable to biological or chemical applications such as continuous perfusion cell culture or biocatalytic synthesis but without the need for any post-device assembly and finishing. The 3D printed devices with embedded Corning(®) Fibrance™ Light-Diffusing Fiber would have applications in display, illumination, or optical applications. Furthermore, the FDM-based 3D printing and embedding method could also be utilized to print casting molds with an integrated glass bottom for polydimethylsiloxane (PDMS) device replication. These 3D printed glass bottom casting molds would result in PDMS replicas with a flat smooth bottom surface for better bonding and adhesion.


A promising change in the selection of the circular polarization excitation used in the measurement of Eu(III) circularly polarized luminescence.
A judicious change in the selected transition used for circular polarization excitation will overcome the low oscillator strength limitation of the currently allowed magnetic-dipole (5)D1 <-- (7)F2 (Eu(III)) transition chosen for circularly polarized luminescence (CPL) measurement. The proposed allowed magnetic-dipole (5)D1 <-- (7)F0 (Eu(III)) transition will facilitate the detection of CPL from the Eu(III) systems of interest. CPL on the acetonitrile solution of the chiral tris complex of Eu(III) with (R,R)-N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide ([Eu((R,R)-1)3](3+)), recently suggested as an effective and reliable CPL calibrating agent, confirms the feasibility of the proposed experimental procedure. A comparable CPL activity exhibited by the acetonitrile solution of [Eu((R,R)-1)3](3+) following direct excitation in the spectral range of the (5)D1 <-- (7)F0 transition and upon indirect excitation through the ligand absorption bands (lambda(exc) = 308 nm) was observed. This confirms that the recommended magnetic-dipole allowed absorption transition, (5)D1 <-- (7)F0, is the transition to be considered in the measurement of CPL. This work provides critical direction for the continued instrumental improvements that can be done for developing CPL into a biomolecular structural probe.


Physicochemical properties affect the synthesis, controlled delivery, degradation and pharmacokinetics of inorganic nanoporous materials.
Controlling size, shape and uniformity of porous constructs remains a major focus of the development of porous materials. Over the past two decades, we have seen significant developments in the fabrication of new, porous-ordered structures using a wide range of materials, resulting in properties well beyond their traditional use. Porous materials have been considered appealing, due to attractive properties such as pore size length, morphology and surface chemistry. Furthermore, their utilization within the life sciences and medicine has resulted in significant developments in pharmaceutics and medical diagnosis. This article focuses on various classes of porous materials, providing an overview of principle concepts with regard to design and fabrication, surface chemistry and loading and release kinetics. Furthermore, predictions from a multiscale mathematical model revealed the role pore length and diameter could have on payload release kinetics.


Determination of oceanic carbon dioxide using a carbonate-selective electrode.
Potentiometric properties of the PVC membrane-based electrodes prepared with molecular tweezer-type neutral carriers, 3,12-bis(TFAB)CA and deoxy-3,12-bis(TFAB)CA, and trifluoroacetyl-p-decylbenzene (TFADB) were measured in buffered electrolytes (0.1 M Tris-H2SO4, pH 8.6 and 8.0) and artificial seawater. It was observed that the deoxy-3,12-bis(TFAB)CA-based electrode provides greatly enhanced carbonate selectivity over chloride (log K(CO3(2-), Cl-)POT approximately -6) and other minor anions present in seawater. Thus, we explored the possibility of applying this new carbonate-selective electrode for direct determination of oceanic carbon dioxide. The total carbon dioxide (TCO2) level in surface Yellow Sea water was determined with the deoxy-3,12-bis(TFAB)CA-based electrode, Severinghaus-type CO2 gas sensor, and the traditional potentiometric titration methods. The results showed that the carbonate-selective electrode provides accurate oceanic TCO2 determination comparable to that obtainable with the other two methods. The analytical procedure based on a carbonate-selective electrode is clearly advantageous over other conventional methods: it does not require any sample pretreatment and extra reagents other than the standard calibration solutions, while providing the measured results directly and immediately.


The cell biology of the blood-brain barrier.
The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (ECs). In the late embryonic and early postnatal period, these cells respond to inducing factors found in the brain environment by adopting a set of defined characteristics, including high-electrical-resistance tight junctions. Although the factors have not been identified definitively, a great deal of information about brain ECs has been obtained, especially recently. This review concentrates on a cell biological analysis of the BBB, with an emphasis on regulation of the specialized intercellular junctions. The development of these junctions seems to depend on two primary processes: the appearance of high levels of the tight junction protein occludin and intracellular signaling processes that control the state of phosphorylation of junctional proteins. Recent studies have revealed that the BBB can be modulated in an ongoing way to respond to environmental stimuli.


Topical steroids eye drops in conjunctival reactive lymphoid hyperplasia: Case report.
Conjunctival lymphoproliferative lesions constitute a significant diagnostic challenge and it is essential to exclude neoplastic lesions. Histopathological and immunohistochemical tests are very useful in establishing the correct diagnosis. Reactive lymphoid hyperplasia (RLH) is part of a spectrum of lymphocytic infiltrative disorders. Evidence is scarce regarding appropriate treatment of conjunctival RLH. We report a case treated with topical corticosteroid. A 40 year-old female presented with a 7-month history of a slow growth tumor in the superior conjunctiva of the right eye. Slit-lamp examination demonstrated salmon colored lesion in the upper conjunctiva, with little conjunctival injection, but no significant neovascularization. There was no eyelid involvement. Ultrasound biomicroscopy showed lesion depth (1.53 mm) and larger diameter (10.73 mm). Pathological examination revealed a chronic inflammatory process with conjunctival folicular hyperplasia. The immunohistochemistry examination showed predominance of CD20, CD23, and CD 3 e CD 5. We started topic prednisolone 1% 6 times daily. Six months after starting treatment, the lesion completely resolved, without any side-effects or recurrence during three-year follow-up period. Conjunctival RLH can be managed in various ways, depending on patient symptonm, comorbities, and disease distribution. Surgical resection with cryotherapy, radiotherapy, systemic corticosteroids, subconjunctival triamcinolone, and rituximab are some options. There is no strong evidence in the literature of conjunctival RLH successfully treated with topical eye drops corticosteroid. In this report, we obtained completely resolution of conjunctival RLH with topical corticosteroid. Topical eye drops corticosteroids are an alternative treatment for selected cases of conjuncitval RLH with no orbital or eyelid involvement.


Evaluation of Fungicide Soil Drench Treatments to Manage Black Root Rot Disease of Avocado.
Four common fungicidal products were evaluated for their effect on symptoms caused by two nectriaceous black root rot fungi, Calonectria ilicicola and Dactylonectria macrodidyma, when applied as pot drenches to avocado (Persea americana) seedlings in the greenhouse. Applications of fludioxonil, thiophanate-methyl + etridiazole, prochloraz, and prochloraz MnCl at 2 and 4 weeks after inoculation with C. ilicicola significantly reduced root necrosis and improved root and aboveground plant biomass compared with water-treated controls. Fludioxonil reduced necrosis by 60% and had a significantly lower frequency of reisolation of C. ilicicola than the other three fungicide treatments. D. macrodidyma inoculation caused less severe symptoms in seedlings than C. ilicicola despite the longer duration of the trial. Pot drenches with fludioxonil, thiophanate-methyl + etridiazole, and prochloraz MnCl, but not prochloraz alone, significantly reduced root necrosis caused by D. macrodidyma. Prochloraz MnCl was the only fungicide treatment to increase root and plant biomass compared with water-treated controls. Both fludioxonil and prochloraz MnCl reduced the frequency of reisolation of D. macrodidyma from necrotic roots by about 50% compared with the other fungicides or water controls. The results indicated that drenches with these fungicides may suppress existing low to moderate black root rot infection, allowing new root growth and improved establishment in the orchard. Fungicide drenching must not replace best-practice disease management strategies in nurseries but may be a useful tool in crisis situations.


Allantoin, a purine metabolite, enhances peripheral nerve regeneration following sciatic nerve injury in rats: A stereological and immunohistochemical study.
Following peripheral nerve injury, in addition to axonal and myelin degeneration, a sharp increase is observed in cell numbers, especially Schwann cells, in the distal part of the injury. This study investigated the effect of allantoin, involved in purine catabolism, on the reactions occurring in the lesion area. An experimental sciatic nerve injury model was established with the application of pressure at 50 Newtons for 5 s to the right sciatic nerves of experimental animals following visualization with the help of pliers. Allantoin was administered to the test groups via the intraperitoneal (i.p.) route (10 mg/kg), at the same time every day for 30 days. The animals were sacrificed at the end of 30 days, following electromyography and Sciatic Function Index tests. Myelinated/unmyelinated axon numbers were evaluated stereologically. Myelin sheath thickness, axon diameter, mitotic activity, and functional improvement in muscles in this peripheral nerve degeneration model were investigated. The test results were then subjected to statistical analysis. Allantoin was observed to exhibit curative effects in terms of function, although stereological tests revealed no morphological differences. The i.p. administration of allantoin may have a beneficial effect on nerve healing.


Ultrasonic assessment in pre-operative cataract patients.
The ability to examine the posterior segment of the eye accurately in patients with opaque media is essential to good surgical care of the cataract patient. In dense cataracts, the posterior segment is inaccessible to direct and indirect ophthalmoscopy and so adequate evaluation of posterior segment to exclude abnormalities become difficult. There is a risk of poor prognosis in eyes of patients with cataracts who may also have co-existing posterior segment abnormalities. Ultrasonography provides a method of assessing the structural changes in the posterior segment of the eye in such patients. To determine the relevance and prevalence of posterior segment abnormalities in patients with dense cataracts prior to surgery by ultrasonography. A 12- month prospective study of patients with clinically diagnosed dense cataracts in either or both eyes, in which the posterior segment cannot be evaluated properly during ophthalmoscopy, and therefore were sent for ocular ultrasonography. B-scan ultrasound was done on 116 eyes of 80 patients. Eighty patients were involved in the study, 116 eyes demonstrated dense cataract. One hundred and ten eyes (94.8%) had a normal posterior segment. Total retinal detachment was noted in 3 eyes (2.59%), a left partial retinal detachment was observed in 1 eye (0.87%), 2 eyes with total retinal detachment in conjunction with vitreous haemorrhage were noted in a single patient, 1.72% Posterior segment assessment with ultrasound is advisable and important in the preoperative evaluation of patients with dense cataract prior to surgery.


Molecular-dynamic studies of carbon-water-carbon composite nanotubes.
We recently reported the discovery via molecular-dynamic simulations that single-walled carbon nanotubes (SWCNTs) with different diameters, lengths, and chiralities can coaxially self-assemble into multi-walled carbon nanotubes (MWCNTs) in water via the spontaneous insertion of smaller tubes into larger ones. Here, we extend that study to investigate the various water structures formed between two selected SWCNTs after such coaxial assembly. Depending on the tube geometry, typical water structures, besides the bulk phase, include a one-dimensional (1D) ordered water chain inside the smaller tube, a uniform or nonuniform water shell between the two tubes, and a "boundary layer" of water near the exterior wall of the larger tube. It was found that a concentric water shell consisting of up to three layers of water molecules can form between the two SWCNTs, which leads to a class of carbon-water-carbon composite nanotubes. Analysis of the potential energy of the SWCNT-water system indicated that the composite nanotubes are stabilized by both the tube-tube and tube-water van der Waals interactions. Geometrically confined between the two SWCNTs, water mono- and bilayers are found to be stable, highly condensed, and ordered, although the average number of hydrogen bonds per water molecule is reduced. In contrast, a water trilayer between the two CNTs can be easily disrupted by thermal fluctuations.


Malignant melanoma metastatic to the mandible.
Metastatic malignant melanoma to the jaws is uncommon and is usually accompanied by generalized involvement. Hematogenous dissemination with deposition and growth in areas of hematopoietic marrow (that is, the mandibular molar region) is the accepted mechanism for involvement of the jaw. Clinical and radiographic findings are nonspecific. Comprehensive history, physical examination, and tissue microscopy are essential to accurate diagnosis and management of the patient. Radiotherapy for palliation is the accepted mode of therapy for symptomatic metastatic melanoma. Prognosis in cases with secondary jaw involvement is grave. A case of malignant melanoma with metastases to the mandible is presented and the literature is reviewed.


Avascular Retinal Findings in a Child With Achondroplasia.
The authors present clinical and angiographic findings in a 12-year-old girl with achondroplasia who presented with bilateral retinal peripheral nonperfusion and unilateral rhegmatogenous retinal detachment, which has not been previously described in achondroplasia. This report contributes incremental knowledge regarding aberrant retinal vascular phenomena observed in pediatric disease states and implicates the possible role of mutations in the FGFR3 gene in peripheral vascular abnormalities. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:272-274.].


Kefir extracts suppress in vitro proliferation of estrogen-dependent human breast cancer cells but not normal mammary epithelial cells.
Anti-tumorigenic effects have been demonstrated in animal studies from the intake of kefir, a traditional fermented milk product believed to originate from the Caucasian mountains of Russia. In the present study, the antiproliferative effects of extracts of kefir, yogurt, and pasteurized cow's milk on human mammary cancer cells (MCF-7) and normal human mammary epithelial cells (HMECs) was investigated at doses of 0.31%, 0.63%, 1.25%, 2.5%, 5%, and 10% (vol/vol). After 6 days of culture, extracts of kefir-fermented milk depressed MCF-7 cell growth in a dose-dependent manner, showing 29% inhibition of proliferation at a concentration as low as 0.63%, whereas yogurt extracts began to show dose-dependent antiproliferative effects only at the 2.5% dose. Moreover, at the 2.5% dose, kefir extracts decreased the MCF-7 cell numbers by 56%, while yogurt extracts decreased MCF-7 cell proliferation by only 14%. No antiproliferative effects of kefir extracts were observed in the HMECs, while the yogurt extracts exerted antiproliferative effects on HMECs at the 5% and 10% doses. Unfermented milk extracts stimulated proliferation of MCF-7 cells and HMECs at concentrations above 0.31%. Peptide content and capillary electrophoresis analyses showed that kefir-mediated milk fermentation led to an increase in peptide concentrations and a change in peptide profiles relative to milk or yogurt. The present findings suggest that kefir extracts contain constituents that specifically inhibit the growth of human breast cancer cells, which might eventually be useful in the prevention or treatment of breast cancer.


Recurrent vulvar melanoma in a patient with neurofibromatosis and gastrointestinal stromal tumour.
We report a case of a 51-year-old woman with neurofibromatosis who presented in 2012 with postmenopausal bleeding. Excision biopsy of a pigmented lesion of the labia minora was consistent with an ulcerated vulvar BRAF wild type malignant melanoma (MM). Initial excision was followed by radical vulvectomy and adjuvant interferon. Local recurrence in January 2017 was further resected. Positron emission tomography (PET)-CT in May 2017 identified an FDG avid omental deposit; consistent histologically with MM when resected. Postoperative PET-CT in August 2017 demonstrated local recurrence. In the setting of resected stage IV disease and a third local recurrence, the decision was made to instigate immunotherapy. Vulvar melanoma is rare accounting for 0.2% of all melanoma. Presentation is typically a decade later than cutaneous melanoma with a tendency to late metastases and poorer prognosis. Given their rarity the treatment paradigm is less clearly defined and largely extrapolated from that of cutaneous melanomas.


Cloning and expression analysis of zygote arrest 1 (Zar1) in New Zealand white rabbits.
Zygote arrest 1 (Zar1) is an oocyte-specific maternal-effect gene. Previous studies indicate that Zar1 plays important role in early embryo development, but little is known about its function in rabbit. The objectives of this study were to clone the New Zealand white rabbit Zar1 gene and to investigate its expression in various organs in groups of animals with different reproductive traits.We obtained a 709-bp Zar1 cDNA fragment consisting of an 8-bp exon 1, 161-bp exon 2, 75-bp exon 3, 271-bp exon 4 and 194-bp 3'sequences. The rabbit Zar1 nucleotide sequence showed per cent identities of 91, 88, 88, 87, 86, 87, 76 and 82% with Zar1 orthologues in human, cattle, sheep, pig, mouse, rat, zebrafish and Xenopus laevis, respectively, indicating a high homology with other species and evolutionary conservation. Quantitative real-time polymerase chain reaction analyses revealed nonoocyte-specific Zar1 expression, with expression in spleen, lung, ovary, uterus, heart, liver and kidney. The expression level was highest in the lung. This study may lay the theoretical foundation for the study of ZAR1's biological function.


[Effects of Qili Qiangxin capsules on NT-proBNP level and cardiac function in silicosis patients].
To investigate the effects of Qili Qiangxin capsules on the amino-terminal pro-brain natriuretic peptide (NT-proBNP) level and cardiac function in patients with silicosis. Hospitalized silicosis patients with heart failure were divided into treatment group (41 cases) and control group (30 cases) according to their own will. Both groups received comprehensive symptomatic treatment; in addition, the treatment group received Qili Qiangxin capsules. The treatment lasted 6 months. The observed items included NT-proBNP level, 6-minute walk test, ultrasonic cardiogram, and NYHA classification before and after treatment. According to NYHA classification, the response rate was 29.27%in the treatment group and 10.00%in the control group; there was a significant difference between the two groups (P < 0.05). The average walk distance in the treatment group was increased from 150.96±73.12 m before treatment to 169.32±77.04 m after treatment, and the improvement was statistically significant (P < 0.05). The average NT-proBNP level in the treatment group was reduced from 1154.44 ± 480.79 ng/L before treatment to 494.49 ± 342.61 ng/L after treatment, and the reduction was statistically significant (P < 0.01). Left ventricular ejection fraction was significantly improved in the treatment group (P < 0.05). Qili Qiangxin capsules in addition to comprehensive symptomatic treatment can significantly reduce NT-proBNP level and improve cardiac function in silicosis patients, and thereby improve patients' quality of life.


[Expression of caspase-8 in non-small cell lung cancer and its role in invasion and metastasis of lung cancer A549 cells].
To explore the expression of caspase-8 in non-small cell lung cancer (NSCLC) tissue, and its role in invasion and metastasis of lung cancer A549 cells. The expression of caspase-8 in the lung cancer tissues was detected by immunohistochemistry. RNA interference technology was used to silence the expression of caspase-8 in lung cancer A549 cells to explore the function of caspase-8 protein in invasion and metastasis of cancer cells by means of Western blot, Transwell and scratch migration assays. The expression of caspase-8 was found in 38/52 cancer tissues, 22/30 adjacent tissues and 34/52 normal tissues. The tissues number of caspase-8 positive-expression in different groups was similar, but the intensity of caspase-8 expression in different groups was statistically different(P<0.05). In cancer tissues, the expression of caspase-8 indicated more likely to have lymph node-metastasis and worse clinical stage(P<0.05). After RNA interference, we successfully silenced the expression of caspase-8 in the lung cancer A549 cell, and this was confirmed by Western blotting. Transwell and cell scratch test showed that without the expression of caspase-8 A549 cells had a lower invasion and metastasis abilities compared to the control cells (P<0.05). Caspase-8 is not only an apoptosis protein, but has non-apoptosis function, such as promoting invasion and metastasis of lung cancer A549 cell. In NSCLC, it more likely locates in nucleus. And its expression in NSCLC may indicate a later clinical stage and a higher probability of lymph node metastasis.


A simple and sensitive method for the determination of fibric acids in the liver by liquid chromatography.
Fibrates are used in biochemical and pharmacological studies as bioactive tools. Nevertheless, most studies have lacked information concerning the concentrations of fibric acids working inside tissues because a simple and sensitive method is not available for their quantitation. This study aimed to develop a simple and sensitive bioanalytical method for the quantitation of clofibric, bezafibric and fenofibric acids in samples of very small portions of tissues. Fibric acids were extracted into n-hexane-ethyl acetate from tissue homogenates (10 mg of liver, kidney or muscle) or serum (100 µL) and were derivatized with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC with fluorescence detection. These compounds were separated isocratically on a reversed phase with acetonitrile-water. Standard analytical curves were linear over the concentration range of 0.2-20 nmol/10 mg of liver. Precision and accuracy were within acceptable limits. Recovery from liver homogenates ranged from 93.03 to 112.29%. This method enabled the quantitation of fibric acids in 10 mg of liver from rats treated with clofibric acid, bezafibric acid or fenofibrate. From these analytical data, it became clear that there was no large difference in ratio of acyl-CoA oxidase 1 (Acox1) mRNA level to fibric acid content in the liver among the three fibric acids, suggesting that these three fibric acids have similar potency to increase expression of the Acox1 gene, which is a target of peroxisome proliferator-activated receptor α. Thus, the proposed method is a simple, sensitive and reliable tool for the quantitation of fibric acids working in vivo inside livers.


Total hip arthroplasty with Boneloc cement: Unsatisfactory results in 163 hips after 9 to 11 years.
Boneloc bone cement was introduced in the Netherlands in 1992. Inferior short-term results were reported which led to the withdrawal of Boneloc from clinical use in 1995. However, little is known about the long-term outcome of hip arthroplasties with Boneloc. Between April 1992 and August 1994, Boneloc was used in 163 Mallory-Head primary total hip arthroplasties in 163 patients. Follow-up analysis was performed in 2003. To date, 27 hips (17%) have been revised for aseptic loosening of the femoral component. Median time to revision was 5.5 years. Survival analysis based on revision for aseptic loosening showed 77% cumulative survival at 11 years. With revision for aseptic loosening and/or definite radiological loosening according to Harris as endpoint, cumulative survival was 59% at 11 years. In 27 of 43 patients with definite radiological loosening, a cement fracture was seen at a median of 2.9 years. These results show failure of Boneloc cemented total hip arthroplasties occurring even during the later follow-up. Continuing periodic clinical and radiological examination is recommended. (Hip International 2004; 14: 229-32).


Solitons in spiraling Vogel lattices.
We address light propagation in Vogel optical lattices and show that such lattices support a variety of stable soliton solutions in both self-focusing and self-defocusing media, whose propagation constants belong to domains resembling gaps in the spectrum of a truly periodic lattice. The azimuthally rich structure of Vogel lattices allows generation of spiraling soliton motion.


A rare case report of early bioprosthetic valve thrombosis presenting with acute heart failure salvaged by thrombectomy.
Bioprosthetic valve thrombosis is previously considered as an extremely rare complication which hasn't been systemically recognized and understood. Herein, we present an unusual case of a patient manifesting with acute heart failure, secondary to thrombus formation in a porcine aortic bioprosthesis which was implanted 11 months prior to hospitalization. Due to the patient's poor heart function and intraoperative findings, thrombectomy was performed. For our best knowledge, cases of early bioprosthetic valve thrombosis presenting with acute heart failure have seldomly been reported. Our study reviews predisposing factors, typical echocardiographic features and treatment for bioprosthetic valve thrombosis and it should be considered as a reason for bioprosthetic malfunction. A combination of clinical and echocardiographic features can help for diagnosis preoperatively. In some certain circumstances, early reoperation can be avoided if anticoagulant therapy works.


Orbital mechanisms of electron-spin manipulation by an electric field.
A theory of spin manipulation of quasi-two-dimensional (2D) electrons by a time-dependent gate voltage applied to a quantum well is developed. The Dresselhaus and Rashba spin-orbit coupling mechanisms are shown to be rather efficient for this purpose. The spin response to a perpendicular-to-plane electric field is due to a deviation from the strict 2D limit and is controlled by the ratios of the spin, cyclotron, and confinement frequencies. The dependence of this response on the magnetic field direction is indicative of the strengths of the competing spin-orbit coupling mechanisms.


Properties of the protein and carbohydrate fractions in immature wheat kernels.
The time course of compositional changes in the polysaccharide and protein fractions, and of changes in protein structural properties, was investigated in grains of two Italian durum wheat cultivars, Ofanto and Duilio, and the pattern of changes was found to be specific to each cultivar. The fructo-oligosaccharide content in ripening kernels was different between cultivars, as was the pattern of starch accumulation. Evaluation of gluten proteins by Western-blotting using broad-specificity anti-gliadin antibodies showed the sudden appearance of immunoreactive proteins during ripening. Protein surface hydrophobicity and thiol content and accessibility were evaluated in conditions apt at assessing changes in protein interaction and/or in aggregative patterns. Proteins in the two cultivars showed differences in their surface hydrophobicity and in their content of accessible thiols. The simultaneous evaluation of changes in the individual components indicates that use of immature grains for the production of functional foods will require accurate monitoring of the rapidly evolving biopolymer patterns, and careful choice of the cultivar.


Recent advances on natural colorants-based intelligent colorimetric food freshness indicators: fabrication, multifunctional applications and optimization strategies.
With the increasing concerns of food safety and public health, tremendous efforts have been concentrated on the development of effective, reliable, nondestructive methods to evaluate the freshness level of different kinds of food. Natural colorants-based intelligent colorimetric indicators which are typically constructed with natural colorants and polymer matrices has been regarded as an innovative approach to notify the customers and retailers of the food quality during the storage and transportation procedure in real-time. This review briefly elucidates the mechanism of natural colorants used for intelligent colorimetric indicators and fabrication methodologies of natural colorants-based food freshness indicators. Subsequently, their multifunctional applications in intelligent food packaging systems like antioxidant packaging, antimicrobial packaging, biodegradable packaging, UV-blocking packaging and inkless packaging are well introduced. This paper also summarizes several optimizing strategies for the practical application of this advanced technology from different perspectives. Strategies like adopting a hydrophobic matrix, constructing double-layer film and encapsulation have been developed to improve the stability of the indicators. Co-pigmentation, metal ion complexation, pigment-mixing and using substrates with high surface area are proved to be effective to enhance the sensitivity of the indicators. Approaches include multi-index evaluation, machine learning and smartphone-assisted evaluation have been proven to improve the accuracy of the intelligent food freshness indicators. Finally, future research opportunities and challenges are proposed. Based on the fundamental understanding of natural colorants-based intelligent colorimetric food freshness indicators, and the latest research and findings from literature, this review article will help to develop better, lower cost and more reliable food freshness evaluation technique for modern food industry.


Thyrotoxicosis-facilitated bridge to recovery with a continuous-flow left ventricular assist device.
The HeartMate II is a continuous-flow left ventricular assist device that can be explanted from patients after cardiac recovery. We implanted a HeartMate II in a 21-year-old man who had idiopathic cardiomyopathy. A year later, he developed thyrotoxicosis, presumably secondary to amiodarone administered for ventricular fibrillation. Four months after the diagnosis of thyrotoxicosis, thyroid hormone levels had returned to normal, and native cardiac function had improved remarkably. After a support period of 24 months, the HeartMate II was explanted. Six years later, the patient continues to be in New York Heart Association functional Class I. Amiodarone-induced thyrotoxicosis may have contributed to myocardial recovery.


Enhancing Hydrophobicity and Oxygen Barrier of Xylan/PVOH Composite Film by 1,2,3,4-Butane Tetracarboxylic Acid Crosslinking.
Hemicellulose has potential advantages in food packaging because of its abundant reserves, degradability and regeneration. However, compared with fossil-derived plastic films, hemicellulose-based films show inferior hydrophobicity and barrier properties because of their low degree of polymerization and strong hydrophilicity. Focusing on such issues, this work covers the modification of a xylan/polyvinyl alcohol (PVOH) film using 1,2,3,4-butane tetracarboxylic acid (BTCA) as esterifying agent. The thus prepared composite film was more compact owing to the esterification reaction with xylan and PVOH forming a crosslinked network structure and reducing the distance between molecular chains. The results showed that BTCA had a positive effect on the oxygen barrier, hydrophobicity and mechanical properties of the composite film. The tensile strength of the xylan/PVOH composite film with 10% BTCA content increased from 11.19 MPa to 13.99 MPa. A 20% BTCA loading resulted in an increase in the contact angle of the composite film from 87.1° to 108.2°, and a decrease in the oxygen permeability from 2.11 to 0.43 (cm3·µm)/(m2·d·kPa), corresponding to increase in the contact angle by 24% and a decrease in oxygen permeability by 80%. The overall performance enhancement indicates the potential application of such composites as food packaging.


Resveratrol inhibits TNF-α-induced IL-1β, MMP-3 production in human rheumatoid arthritis fibroblast-like synoviocytes via modulation of PI3kinase/Akt pathway.
Resveratrol (trans-3,4'-trihydroxystilbene), a natural phytoalexin, possesses anti-inflammatory, anti-proliferative, and immunomodulatory properties and has the potential for treating inflammatory disorders. The present study was designed to investigate the effects of resveratrol on TNF-α-induced inflammatory cytokines production of IL-1β and MMP3 in Rheumatoid arthritis (RA) Fibroblast-like synoviocytes (FLS) and further to explore the role of PI3K/Akt signaling pathway by which resveratrol modulates those cytokines production. The levels of IL-1β, MMP-3 in cultural supernatants among groups were measured by enzyme-linked immunosorbent assay. Messenger RNA expression of IL-1β and MMP-3 in RA FLS was analyzed using a reverse transcription-polymerase chain reaction. Western blot analysis was used to detect proteins expression in RA FLS intervened by resveratrol. Resveratrol inhibited both mRNA and proteins expressions of IL-1β and MMP-3 on RA FLS in a dose-dependent manner. Resveratrol also decreased significantly the expression of phosphorylated Akt dose dependently. Activation of PI3K/Akt signaling pathway exists in TNF-α-induced production of IL-1β and MMP3 on RA FLS, which is hampered by PI3K inhibitor LY294002. Immunofluorescence staining showed that TNF-α alone increased the production of P-Akt, whereas LY294002 and 50 μM resveratrol suppressed the TNF-α-stimulated expression of P-Akt. Resveratrol attenuates TNF-α-induced production of IL-1β and MMP-3 via inhibition of PI3K-Akt signaling pathway in RA FLS, suggesting that resveratrol plays an anti-inflammatory role and might have beneficial effects in preventing and treating RA.


Plasmodesmata-Mediated Cell-to-Cell Communication in the Shoot Apical Meristem: How Stem Cells Talk.
Positional information is crucial for the determination of plant cell fates, and it is established based on coordinated cell-to-cell communication, which in turn is essential for plant growth and development. Plants have evolved a unique communication pathway, with tiny channels called plasmodesmata (PD) spanning the cell wall. PD interconnect most cells in the plant and generate a cytoplasmic continuum, to mediate short- and long-distance trafficking of various molecules. Cell-to-cell communication through PD plays a role in transmitting positional signals, however, the regulatory mechanisms of PD-mediated trafficking are still largely unknown. The induction and maintenance of stem cells in the shoot apical meristem (SAM) depends on PDmediated cell-to-cell communication, hence, it is an optimal model for dissecting the regulatory mechanisms of PD-mediated cell-to-cell communication and its function in specifying cell fates. In this review, we summarize recent knowledge of PD-mediated cell-to-cell communication in the SAM, and discuss mechanisms underlying molecular trafficking through PD and its role in plant development.


Spontaneous Fusion After Cervical Disc Arthroplasty: A Case Report and Literature Review.
To report a rare case of spontaneous fusion (SF) following cervical disc arthroplasty (CDA), to review the related literature, and to propose a new measure to prevent it. The course of a patient with SF is described here. The potential causes, risk factors, and preventive measure of SF after CDA published in previous studies have also been reviewed and discussed. A 63-year-old man presented with a 6-month history of progressive neck pain and developed left C-7 radiculopathy 4 years ago. Magnetic resonance imaging revealed disc herniation at the C6-C7 levels resulting in compression of the left C-7 nerve root. The patient underwent CDA at the C6-C7 levels, during which a PRESTIGE cervical disc device was implanted. He failed to follow-up regularly as recommended postoperatively because he was completely free from the pain in his neck and left upper limb. Four years later, he was readmitted with a 2-month history of occasional neck stiffness. Plain radiographs indicated complete radiographic fusion of the C6-C7 levels with trabecular bone bridging surrounding the cervical disc prosthesis, and dynamic imaging showed no motion. He was seen at regular follow-up visits for up to 60 months without special treatment, as his symptoms of neck stiffness were minor and his symptom has not worsened since then. SF after CDA is a rare condition that can be attributed to patient- or prosthesis-related causes, and its risk factors are diverse. SF after CDA did not affect the patient's clinical outcome, and no special treatment was required for it. Practitioners should be aware of this rare complication and advise patients of the risks before performing CDA.


Deep Multi-Branch Two-Stage Regression Network for Accurate Energy Expenditure Estimation With ECG and IMU Data.
Energy Expenditure (EE) estimation plays an important role in objectively evaluating physical activity and its impact on human health. EE during activity can be affected by many factors, including activity intensity, individual physical and physiological characteristics, environment, etc. However, current studies only use very limited information, such as heart rate and step count, to estimate EE, which leads to a low estimation accuracy. In this study, we proposed a deep multi-branch two-stage regression network (DMTRN) to effectively fuse a variety of related information including motion information, physiological characteristics, and human physical information, which significantly improved the EE estimation accuracy. The proposed DMTRN consists of two main modules: a multi-branch convolutional neural network module which is used to extract multi-scale context features from electrocardiogram (ECG) and inertial measurement unit (IMU) data, and a two-stage regression module which aggregated the extracted multi-scale context features containing the physiological and motion information and the anthropometric features to accurately estimate EE. Experiments performed on 33 participants show that our proposed method is more accurate and the average root mean square error (RMSE) is reduced by 22.8% compared with previous works. The EE estimation accuracy was improved by the proposed DMTRN model with a well-designed network structure and new input signal ECG. This study verified that ECG was much more effective than HR for EE estimation and cast light on EE estimation using the deep learning method.


Household physical activity and subjective well-being: An international comparison among East Asian older adult populations.
Engaging in lifelong physical activity has multiple health benefits for older populations. Household physical activity occupies older adults' awake time, and they can be an important energy expenditure during the day. The purpose of this study was to investigate the association between older adults' household physical activity and subjective well-being in four East Asian societies. The study design was a secondary data analysis. Data were retrieved from the module of Families 2016 in the database of the East Asian Social Survey. Participants were community-dwelling older adults with a mean age of 70.30±7.50 years and who lived in China, Japan, Korea, and Taiwan. Data were collected by interviews via structured questionnaires between 2016 and 2018. Descriptive analyses, independent t-tests, and an analysis of covariance were performed for the statistical analyses. In total, there were 3,432 valid responses. Participants who lived in Taiwan had significantly lower levels of total household physical activity than those living in other societies. Older adults' household physical activity was found to significantly differ by age, educational degree, gender, religion, marital status, occupation, and whether living alone. Older adults with high levels of household physical activity had significantly higher self-rated health and marital satisfaction than those with low levels. Household physical activity has potential benefits for subjective well-being across international older adult populations. Increasing household physical activity is recommended for older married couples to maintain marital satisfaction.


The role of the sulfinyl group on the course of the reactions of 3-p-tolylsulfinylfuran-2(5H)-ones with nitrones. synthetic uses of cycloreversion processes.
[reaction: see text] The reaction of enantiopure 3-p-tolylsulfinylfuran-2(5H)-ones (2a and 2b) with cyclic (4) and acyclic (6) nitrones afforded furoisoxazolidines (5 and 7) in high yields under mild conditions. The reactivity of the dipolarophile was dramatically enhanced by the sulfinyl group, which modulated the pi-facial selectivity (it was complete for reactions from 2b, yielding only the anti adducts) and was the main controller of the endo/exo selectivity. Cycloreversion processes from the resulting sulfinyl furoisoxazolidines proceeded readily and were to be considered to account for an improvement in the selectivity (facial and endo/exo) and even for an inversion of it when the composition of the reaction mixtures obtained under kinetic and thermodynamic conditions were quite different.


Ultrastructural evaluation of the effects of the contrast media on the rat kidney.
In this study, the ultrastructural observations in rat kidneys were studied 2, 24 and 48 h after intravenous injection of 1, 3 and 9 g iodine per kg body of ioxaglate and iohexol. The effect of the contrast media was mainly on the proximal convoluted tubule cells, the presence of vacuoles containing granular and membranous structures was a striking feature. In the distal convoluted tubular cells, pycnotic nuclei and cytoplasmic bulges toward the lumen were observed. In some glomeruli, membranous structures in cytoplasm of podocytes and thickening of glomerular basal membrane were seen. Values of biochemical analysis were slightly higher especially at high doses in experimental groups when compared to the control. The results suggest that iohexol causes more degeneration than ioxaglate. Not only proximal convoluted tubule cells but also the other parts of the nephron were affected by contrast media.


Simple algorithms for predicting psychotropic drugs assigned to psychiatric inpatients.
The ability of simple algorithms, primarily diagnostic, to assign classes of psychotropic drugs to psychiatric inpatients in agreement with actual clinical decisions was investigated. Overall agreement (hit-rates) ranging from 48 to 65 percent were found across four major drug groups: major tranquilizer, antidepressant, minor tranquilizer, and no psychotropic drug. These hit-rates may be compared with multivariate formulae developed in earlier studies that achieved hit-rates ranging from 62 to 77 percent. Agreement among clinicians (about 70 percent) appears to be the limiting factor in most studies of this type.


A method for detecting the effect of magnetic field on activity changes of neuronal populations of Morimus funereus (Coleoptera, Cerambycidae).
Modification of a new method for detecting changes in the activities of neuronal population and the nearest neuron is described. Preliminary measurements of the influence of a static magnetic field (2 mT) on neuronal population activity on eight individuals of an endangered insect species Morimus funereus are included. Five minutes exposure produced both excitatory (5/8) and inhibitory (3/8) effect on the activity of neuronal population of M. funereus antennal lobe. However, when the reversibility of induced effects was quantitatively analyzed, our results showed that they were prevailingly irreversible: (7/8) for the population, (6/8) for the nearest neuron.


New ways to successfully target tumor vasculature in ovarian cancer.
The aim of this article was to review the recent literature on potential therapeutic strategies for overcoming resistance to antivascular endothelial growth factor drugs in ovarian cancer. Although clinical benefits of antivascular endothelial growth factor therapy were observed in ovarian cancer treatment trials, this use yielded only modest improvement in progression-free survival and, with the exception of cediranib, no effect on overall survival. Adaptive resistance and escape from antiangiogenesis therapy is likely a multifactorial process, including induction of hypoxia, vascular modulators, and immune response. New drugs targeting the tumor vasculature or other components of the surrounding microenvironment have shown promising results. When to start and end antiangiogenesis therapy and the choice of optimal treatment combinations remain controversial. Further evaluation of personalized novel angiogenesis-based therapy is warranted. Defining the critical interaction of these agents and pathways and the appropriate predictive markers will become an increasingly important objective for effective treatment.


Successful and safe treatment of hemangioma with oral propranolol in a single institution.
Dramatic improvement of hemangioma to propranolol has been recently reported; however, details on dose and duration of treatment, potential risks, and monitoring have not been determined. The objective of this study is to describe and analyze the use of propranolol as a first-line treatment or as a single therapy in management of complicated hemangioma. A retrospective chart review of eight patients diagnosed with hemangioma and treated with propranolol in Kangbuk Samsung Hospital from February 2010 to April 2011 was performed. Eight patients with hemangioma with functional impairment, cosmetic disfigurement, or rapid growth were treated with propranolol. Five patients had solitary facial hemangioma. The mean age of symptoms at onset was 5 weeks. The median age for starting propranolol treatment was 5.5 months. Propranolol at 2 mg/kg/day was finally administered in divided doses with a gradual increase. Significant regression was observed in seven patients, and shrinkage in size, softening in consistency, and decrease in redness were evident within 4 weeks. Among them, six patients were still taking propranolol, and one patient had stopped after 12 months. Other one patient did not show significant improvement with satisfactory result after 3 months of propranolol use. Treatment with propranolol was well tolerated and had few side effects. No rebound growth was observed in any of the patients. We observed that use of propranolol was very effective in treatment of hemangioma without obvious adverse effects or relapse.


[Jejunal free flap for reconstruction of the hypopharynx].
Squamous cell carcinoma of the hypopharynx is an aggressive tumor with a bad prognosis. When the tumor is resected it is necessary to reconstruct the hypopharynx and the esophagus. Today, reconstruction with a jejunal free flap is considered to be the preferred option. We present a series of five patients with squamous cell carcinoma of the hypopharynx operated on at the Department of Otolaryngology in the Rabin Medical Center. All underwent total laryngopharyngectomy and reconstruction with a jejunal free flap. Three patients resumed total enteral nutrition about two weeks post surgery. One patient suffered from a pharyngocutaneous fistula and continued parenteral nutrition via a jejunostomy. One patient suffered from necrosis of the flap, which necessitated its resection. Despite the morbidity which follows surgery of the hypopharynx and despite the low cure rates, a successful reconstruction with jejunal free flap enables the resumption of oral nutrition and improvement in the patients quality of life.


A crucial role for primary cilia in cortical morphogenesis.
Primary cilia are important sites of signal transduction involved in a wide range of developmental and postnatal functions. Proteolytic processing of the transcription factor Gli3, for example, occurs in primary cilia, and defects in intraflagellar transport (IFT), which is crucial for the maintenance of primary cilia, can lead to severe developmental defects and diseases. Here we report an essential role of primary cilia in forebrain development. Uncovered by N-ethyl-N-nitrosourea-mutagenesis, cobblestone is a hypomorphic allele of the IFT gene Ift88, in which Ift88 mRNA and protein levels are reduced by 70-80%. cobblestone mutants are distinguished by subpial heterotopias in the forebrain. Mutants show both severe defects in the formation of dorsomedial telencephalic structures, such as the choroid plexus, cortical hem and hippocampus, and also a relaxation of both dorsal-ventral and rostral-caudal compartmental boundaries. These defects phenocopy many of the abnormalities seen in the Gli3 mutant forebrain, and we show that Gli3 proteolytic processing is reduced, leading to an accumulation of the full-length activator isoform. In addition, we observe an upregulation of canonical Wnt signaling in the neocortex and in the caudal forebrain. Interestingly, the ultrastructure and morphology of ventricular cilia in the cobblestone mutants remains intact. Together, these results indicate a critical role for ciliary function in the developing forebrain.


Two-dimensional echocardiographic assessment of normal fetal cardiac anatomy.
The fetal heart is visualized routinely during the antepartum ultrasound examination. Because of the advent of high-resolution, real-time ultrasound instruments, details of fetal cardiac anatomy can now be defined. Fifty consecutive fetuses were examined in utero to assess the ability of two-dimensional echocardiography to define intracardiac anatomy at various gestational ages. A complete examination required at least three standard echocardiographic views of the heart: four-chamber, short-axis and long-axis views. In 30 of the 50 fetuses studied (60%) only one examination was necessary to obtain this information. Ten patients had a second examination later in gestation that complemented the findings of their first study. In all but two fetuses, detection of all four cardiac chambers and at least one semilunar valve was possible. Mitral-semilunar valve continuity was detected in all. The quality of echocardiographic imaging was enhanced by the fetal occiput posterior position (three views obtained in 83% of the fetuses studied). Breech position did not affect imaging quality. Prior to 30 weeks of gestation, fetal movement hampered analysis of fetal cardiac anatomy in some patients.


[BIOINFORMATICS COMPARISON OF HUMAN AND PLANT PHOSPHATOMES].
The study presents the results of bioinformatic comparison of protein phosphatases from higher plants and human phosphatom (150 sequences). Based on sequence and profile comparison with known catalytic domains, 204 plant homologues from Physcomitrella patens and Arabidopsis thaliana where selected. Clustering of joint group of plant and mammalian protein phosphatases revealed fundamental differences in plant and human phosphatomes. At the same time, it was shown significant differences in the set of protein phosphatases in P. patens, A. thaliana, and such monocots as Orysa saliva and Zea mays.


Insights into peculiar fungal LPMO family members holding a short C-terminal sequence reminiscent of phosphate binding motifs.
Lytic polysaccharide monooxygenases (LPMOs) are taxonomically widespread copper-enzymes boosting biopolymers conversion (e.g. cellulose, chitin) in Nature. White-rot Polyporales, which are major fungal wood decayers, may possess up to 60 LPMO-encoding genes belonging to the auxiliary activities family 9 (AA9). Yet, the functional relevance of such multiplicity remains to be uncovered. Previous comparative transcriptomic studies of six Polyporales fungi grown on cellulosic substrates had shown the overexpression of numerous AA9-encoding genes, including some holding a C-terminal domain of unknown function ("X282"). Here, after carrying out structural predictions and phylogenetic analyses, we selected and characterized six AA9-X282s with different C-term modularities and atypical features hitherto unreported. Unexpectedly, after screening a large array of conditions, these AA9-X282s showed only weak binding properties to cellulose, and low to no cellulolytic oxidative activity. Strikingly, proteomic analysis revealed the presence of multiple phosphorylated residues at the surface of these AA9-X282s, including a conserved residue next to the copper site. Further analyses focusing on a 9 residues glycine-rich C-term extension suggested that it could hold phosphate-binding properties. Our results question the involvement of these AA9 proteins in the degradation of plant cell wall and open new avenues as to the divergence of function of some AA9 members.


Defining the biomechanical and biological threshold of murine mild traumatic brain injury using CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration).
CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a recently described animal model of traumatic brain injury (TBI) that primarily produces diffuse axonal injury (DAI) characterized by white matter inflammation and axonal damage. CHIMERA was specifically designed to reliably generate a variety of TBI severities using precise and quantifiable biomechanical inputs in a nonsurgical user-friendly platform. The objective of this study was to define the lower limit of single impact mild TBI (mTBI) using CHIMERA by characterizing the dose-response relationship between biomechanical input and neurological, behavioral, neuropathological and biochemical outcomes. Wild-type male mice were subjected to a single CHIMERA TBI using six impact energies ranging from 0.1 to 0.7J, and post-TBI outcomes were assessed over an acute period of 14days. Here we report that single TBI using CHIMERA induces injury dose- and time-dependent changes in behavioral and neurological deficits, axonal damage, white matter tract microgliosis and astrogliosis. Impact energies of 0.4J or below produced no significant phenotype (subthreshold), 0.5J led to significant changes for one or more phenotypes (threshold), and 0.6 and 0.7J resulted in significant changes in all outcomes assessed (mTBI). We further show that linear head kinematics are the most robust predictors of duration of unconsciousness, severity of neurological deficits, white matter injury, and microgliosis following single TBI. Our data extend the validation of CHIMERA as a biofidelic animal model of DAI and establish working parameters to guide future investigations of the mechanisms underlying axonal pathology and inflammation induced by mechanical trauma.


PANDAS with catatonia: a case report. Therapeutic response to lorazepam and plasmapheresis.
This is a report of an 11-year-old, prepubertal boy with acute-onset urinary urgency and frequency, obsessions and compulsions related to urination, severe mood lability, inattention, impulsivity, hyperactivity, and intermittent periods of immobilization. Fever, cough, otitis, and sinusitis preceded neuropsychiatric symptoms. Antistreptolysin O and DNAse B antibody titers were elevated, and magnetic resonance imaging revealed bilateral diffuse caudate nuclei swelling. Plasmapheresis resulted in significant and rapid clinical improvement of obsessive-compulsive disorder symptoms and a simultaneous decrease in basal ganglia swelling, consistent with an immune-mediated pathophysiological process involving group A beta-hemolytic streptococci. Hyperactivity, impulsivity, and inattention improved with lorazepam, suggesting that the attention-deficit/hyperactivity disorder symptoms could be manifestations of catatonia.


Cardiomyopathy is independent of skeletal muscle disease in muscular dystrophy.
Dystrophin and its associated proteins, the sarcoglycans, are normally expressed in heart and skeletal muscle. Mutations that alter the expression of these membrane-associated proteins lead to muscular dystrophy (MD) and cardiomyopathy in humans. Because of the timing and nature of the accompanying cardiomyopathy, it has been suggested that cardiomyopathy develops as a secondary consequence of skeletal muscle dysfunction in the muscular dystrophies. To determine whether skeletal muscle dystrophy contributes to the development of sarcoglycan-mediated cardiomyopathy, we used mice lacking gamma-sarcoglycan and inserted a transgene that "rescued" gamma-sarcoglycan expression only in skeletal muscle. Gamma-sarcoglycan was expressed in skeletal muscle under the control of the skeletal muscle-specific myosin light chain 1/3 promoter. Gamma-sarcoglycan-null mice expressing this transgene fully restore gamma-sarcoglycan expression. Furthermore, the transgene-rescued mice lack the focal necrosis and membrane permeability defects that are a hallmark of MD. Despite correction of the skeletal muscle disease, focal degeneration and membrane permeability abnormalities persisted in cardiac muscle, and notably persisted in the right ventricle. Therefore, heart and skeletal muscle defects are independent processes in sarcoglycan-mediated muscular dystrophies and, as such, therapy should target both skeletal and cardiac muscle correction to prevent sudden death due to cardiomyopathy in the muscular dystrophies.


Mutation in the protozoan Paramecium multimicronucleatum as a result of x-irradiation.
Mutations have been produced in the protozoan Paramecium multimicronucleatum by repeatedly exposing clonal cultures of the animals to large dosages of x-irradiation. The descendants of x-rayed survivors showed the following changes, which persisted in culture: destruction and loss of all micronuclei, decrease in vitality and reproductive rate, increase in x-radiation sensitivity, monstrosity, and reduced body size.


Risk assessment and serotonin: Animal models and human psychopathologies.
Risk assessment (RA) is an evolved, generally adaptive, mechanism comprising focused attention and appraisal of potential threat stimuli and situations. Initially characterized in animal models, it provides a number of behavioral and functional parallels to patterns of rumination, gaze biases, and other forms of affective cognition that appear to be disregulated in depression and anxiety. Serotonergic mechanisms are involved in these mood disorders, and an emerging body of evidence suggests that they may modulate the affective cognitive changes common to such psychopathologies. Findings of parallel effects of serotonin systems in RA would support a view that it may provide a useful behavioral endophenotype for translational research on mood disorders. This review examines the involvement of serotonergic mechanisms in both animal models of RA, and in an array of tasks focusing on affective cognitive changes in individuals with depression or anxiety. Results suggest substantial serotonin involvement in both RA behaviors measured in rats or mice, and in the "intersection of emotional and cognitive processes" [43] in people.


Fresh preservation of alfalfa sprouts and mushroom slices by soaking with thymol and resveratrol solutions.
The preservation of fresh produce served as salads through soaking with solutions containing naturally occurring phenolic ingredients is of merit. For a primary assay, thymol and resveratrol at 0-500 ppm were prepared and used to inhibit growth and survival of Escherichia coli and Staphylococcus aureus. Thymol and resveratrol exhibited potent inhibitory activities against the growth of both bacteria. For S. aureus, cells treated with thymol at 250 ppm or resveratrol at 500 ppm, the durations to achieve 3 log reduction (3LR) were 40 and 20 min, respectively. When the cells were treated with thymol combined with resveratrol, both at 250 ppm, the 3LR value was achieved in under 5 min. Synergistic antibacterial activity between thymol and resveratrol was apparent. The antibacterial and known health-enhancing activities of resveratrol are of interest.


Prevention of caries and obesity in children with immigrant background in Norway- a study protocol for a cluster randomized controlled trial.
Immigrants are known to experience greater socioeconomic stress and poorer well-being and to suffer more from lifestyle- and diet-related disorders than native populations. There is also evidence that children of immigrant parents are at greater risk of diverse health problems than their host country cohorts. The aim of this study is to apply and evaluate the efficacy of an early life intervention program among parents/children with immigrant background to prevent childhood caries and obesity, thereby improving the children's general health, oral health, and quality of life. This is a study protocol for a cluster randomized controlled intervention follow-up study. In phase I of the study, the primary care health centers in the municipality of Bergen, Norway were randomly allocated to intervention or control groups. The intervention was carried out using the motivational interviewing technique and the common risk factor approach. The intervention group received guidance on diet/oral hygiene and the control group received standard care information. Parental knowledge and children at age 3 and 5 years old will be assessed in a prospective phase II follow-up study compared to native Norwegian controls. The primary outcome will be evaluation of change on parental oral health related knowledge and attitudes. The secondary outcome will assess the impact of the intervention on children's caries -, body mass index- and oral health related quality of life. Collaboration between dental public health and primary health care personnel on the common risk approach motivational intervention offers opportunities to address key dietary behaviors that may prevent obesity and dental caries. Providing sustainable preventive measures decreases the burden of diseases and consequently reduces health inequalities, particularly among at-risk children. The study is registered as a clinical trial (ClinicalTrials.gov Identifier: NCT05758454: 7 March 2023). Ethical approval has already been granted by the Regional Ethical Committee (REK) (2015/ 27,639 /REK vest) and Sikt - Norwegian Agency for Shared Services in Education and Research (Reference number 778825).


[Stress and alcohol: research with experimental animals].
Research on the interaction of ethanol and stress with experimental animals are briefly reviewed. There might be the two aspects of the interaction of stress and ethanol, i.e., how stress affects ethanol ingestion and response to ethanol, and how ethanol modifies stress response. In general, stress increases ingestion of ethanol in animals exposed to various stresses including electric shock, immobilization and psychological or emotional stresses, wherein the psychological or emotional factors were predominantly involved. However, in most cases, ethanol ingestion is increased after release from stress not during exposure to stress. A variety of stressful stimuli caused marked increases in the neurotransmitter release in many brain regions. Immobilization stress increased noradrenaline release in the extended brain regions in rats. These increases were significantly attenuated by pretreatment with ethanol in the rat amygdala and locus coeruleus, but not in the hypothalamus, although ethanol by itself increased noradrenaline release in the hypothalamus. Further, psychological stress, wherein the rats were given no electrical shock, but exposed to the emotional responses such as struggling, vocalization, jumping and defecation shown by the other electrically-shocked rats, increased noradrenaline release preferentially in the hypothalamus, amygdala and locus coeruleus. Among the former two regions, stress-induced increases in noradrenaline release were significantly attenuated by ethanol in the amygdala, but not in the hypothalamus. Together with the finding that increases, in noradrenaline release are closely related to the provocation of anxiety and/or fear, ethanol, in part, reduced tension, as mentioned in the tension reduction hypothesis, by attenuating stress-induced increases in noradrenaline release in the amygdala and locus coeruleus. Moreover, ethanol, administered i.p. and directly through the microdialysis probe, increased dopamine release in the nucleus accumbens assessed by in vivo microdialysis, similarly as addictive drugs such as amphetamine did. This might be, in part, neurochemical basis for motivation of repeated drinking of ethanol.


A Case of Chronic Thromboembolic Pulmonary Hypertension.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe complication of incomplete resolution of large pulmonary embolism (PE).Transthoracic echocardiography (TTE) and chest computed tomography (CT) are useful for the diagnosis and follow-up of CTEPH. We report a case of 40-year-old male who wasadmitted with gradually aggravated dyspnea in recent 2 years and had history of acute PE 10 years ago, was detected CTEPH by TTE and confirmed with chest CT.


HCG-responsive aldosteronoma with transient secretion during pregnancy confirmed through HCG-stimulated adrenal venous sampling.
Primary aldosteronism can be regulated by the ectopic expression of G-protein coupled receptors in aldosteronomas or bilateral hyperplasias. We report a rare case of a young woman in whom 2 pregnancies were complicated by pre-eclampsia and 1 miscarriage. The transient primary aldosteronism during pregnancies suggested the possibility of HCG stimulated aberrant adrenal expression of LHCG receptor in her adrenal tissues. This was supported by increased aldosterone and renin suppression during 5-day HCG stimulation test outside of pregnancy. Following a second 5-day HCG stimulation test, bilateral simultaneous adrenal vein sampling identified a lateralized source of aldosterone from an 8 mm right adrenal nodule. A right laparoscopic adrenalectomy resulted in clinical and biochemical cure and allowed a further uneventful pregnancy a few years later. This case illustrates the indication to investigate for potential primary aldosteronism in woman with transient hypertension during pregnancy.


Identification, characterization, and function analysis of the NF-κB repressing factor (NKRF) gene from Litopenaeus vannamei.
The NF-κB family transcription factors regulate a wide spectrum of biological processes, in particular immune responses. The studies in human suggest that the NF-κB repressing factor (NKRF) negatively regulates the activity of NF-κB through a direct protein-protein interaction. However, the function of NKRF has not been studied outside mammals up to now. The current study identified a NKRF gene (LvNKRF) from the Pacific white shrimp, Litopenaeus vannamei, which showed homology with NKRFs from insects, fishes and mammals. LvNKRF was high expressed in intestine, stomach and muscle tissues and was localized in the nucleus. LvNKRF could interact with both Dorsal and Relish, the two members of the shrimp NF-κB family. Interestingly, although sharing a similar protein structure with that of human NKRF, LvNKRF showed no inhibitory but instead enhancing effects on activities of Dorsal and Relish, which was contrary to those of mammalian NKRFs. The expression of LvNKRF could not be induced by Gram-positive and -negative bacteria and immunostimulants lipopolysaccharide (LPS) and poly (I:C) but was significantly up-regulated after white spot syndrome virus (WSSV) infection. Silencing of LvNKRF significantly decreased the mortalities of shrimp caused by WSSV infection and down-regulated the WSSV copies and the expression of WSSV structural gene in tissues. These suggested that LvNKRF could facilitate the infection of shrimp by WSSV, which may be an additional strategy for WSSV to hijack the host NF-κB pathway to favor its own replication. The current study could provide a valuable context for further investigating the evolutionary derivation of NKRFs and facilitate the study of regulatory mechanisms of invertebrate NF-κB pathways.


Cold-water immersion decreases cerebral oxygenation but improves recovery after intermittent-sprint exercise in the heat.
This study examined the effects of post-exercise cooling on recovery of neuromuscular, physiological, and cerebral hemodynamic responses after intermittent-sprint exercise in the heat. Nine participants underwent three post-exercise recovery trials, including a control (CONT), mixed-method cooling (MIX), and cold-water immersion (10 °C; CWI). Voluntary force and activation were assessed simultaneously with cerebral oxygenation (near-infrared spectroscopy) pre- and post-exercise, post-intervention, and 1-h and 24-h post-exercise. Measures of heart rate, core temperature, skin temperature, muscle damage, and inflammation were also collected. Both cooling interventions reduced heart rate, core, and skin temperature post-intervention (P < 0.05). CWI hastened the recovery of voluntary force by 12.7 ± 11.7% (mean ± SD) and 16.3 ± 10.5% 1-h post-exercise compared to MIX and CONT, respectively (P < 0.01). Voluntary force remained elevated by 16.1 ± 20.5% 24-h post-exercise after CWI compared to CONT (P < 0.05). Central activation was increased post-intervention and 1-h post-exercise with CWI compared to CONT (P < 0.05), without differences between conditions 24-h post-exercise (P > 0.05). CWI reduced cerebral oxygenation compared to MIX and CONT post-intervention (P < 0.01). Furthermore, cooling interventions reduced cortisol 1-h post-exercise (P < 0.01), although only CWI blunted creatine kinase 24-h post-exercise compared to CONT (P < 0.05). Accordingly, improvements in neuromuscular recovery after post-exercise cooling appear to be disassociated with cerebral oxygenation, rather reflecting reductions in thermoregulatory demands to sustain force production.


New immunofluorescence method for the identification of group a, b, c, e, and g streptococci.
An immunofluorescence method for the identification of groups A, B, C, E, F, and G beta-haemolytic streptococci has been developed, using FITC-labelled F(ab')2 fragments of IgG with optimal staining characteristics. The method is useful for the rapid confirmation of beta-haemolytic streptococci in cultures; in a blind comparison with Lancefield grouping, there was a 97 per cent agreement.


A Chronic Ocular-Hypertensive Rat Model induced by Injection of the Sclerosant Agent Polidocanol in the Aqueous Humor Outflow Pathway.
To induce a moderate chronic ocular hypertension (OHT) by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway. Intraocular pressure (IOP) was monitored for up to 6 months. Pattern and full-field electroretinogram (PERG and ERG) were recorded and retinal ganglion cells (RGC) and retinal nerve fiber layer (RNFL) thickness were assessed in vivo with optical coherence tomography (OCT) and ex vivo using Brn3a immunohistochemistry. In the first 3 weeks post-injection, a significant IOP elevation was observed in the treated eyes (18.47 ± 3.36 mmHg) when compared with the control fellow eyes (12.52 ± 2.84 mmHg) (p < 0.05). At 8 weeks, 65% (11/17) of intervention eyes had developed an IOP increase >25% over the baseline. PERG responses were seen to be significantly reduced in the hypertensive eyes (2.25 ± 0.24 µV) compared to control eyes (1.44 ± 0.19 µV) (p < 0.01) at week 3, whereas the ERG components (photoreceptor a-wave and bipolar cell b-wave) remained unaltered. By week 24, RNFL thinning and cell loss in the ganglion cell layer was first detected (2/13, 15.3%) as assessed by OCT and light microscopy. This novel OHT rat model, with moderate levels of chronically elevated IOP, and abnormal PERG shows selective functional impairment of RGC.


Primary care doctors' practice in the management of adult asthma patients.
There is apparent disparity between the international guidelines on asthma management and the current practice in reality. This can be attributed to both patient's and doctor's factors. This study examines the practice of asthma management by a group of family physicians using a self-administered questionnaire. This comprises questions relating to the main principles of asthma management set by international guidelines. The results showed that majority of the doctors (>90%) in the study reviewed patient's asthma status based on symptoms, educate their patients on types of asthma medications and advised them on allergen avoidance including smoking. Fewer of them (50 to <90%) check trigger factors or inhaled device technique, nocturnal symptoms or ER visits. Even fewer doctors (<50%) bothered to check the patient's peak expiratory flow rate (PEFR) or used spirometry.


Intracellular RNAs of the feline infectious peritonitis coronavirus strain 79-1146.
In Felis catus whole foetus D cells infected with feline infectious peritonitis virus (FIPV), strain 79-1146, six virus-specific, poly(A)-containing RNA species of about 20, 9.6, 5.2, 3.8, 2.8 and 1.6 kb were found. By translation in vitro the 3.8 and 2.8 kb RNAs were shown to encode the 25K envelope protein and the 45K nucleocapsid protein, respectively. The partial map of the FIPV genome was compared with genomic maps of porcine, murine and avian coronaviruses. Differences in these maps suggest that transcription units have been lost or gained during coronavirus divergence.


BAO-Ag-NPs as Promising Suppressor of ET-1/ICAM-1/VCAM-1 Signaling Pathway in ISO-induced AMI in Rats.
Acute myocardial infarction (AMI) is the most prevalent cause of myocardial fibrosis and the leading cause of mortality from cardiovascular disease. The goal of this work was to synthesize Balanites aegyptiaca oil-silver nanoparticles (BAO-Ag-NPs) and evaluate their cardioprotective effect against ISO-induced myocardial infarction in rats, as well as their mechanism. BAO was isolated, and the unsaturated fatty acids were estimated. BAO-Ag-NPs was prepared, LD50 was calculated to evaluate its cardioprotective activity against ISO (85 mg/kg)- induced AMI. Different doses of BAO-Ag-NPs (1/50 LD50; 46.6 mg/kg.b.w and 1/20 LD50; 116.5 mg) were received to the rats. The total fatty acids and unsaturated fatty acids generated by BAO were 909.63 and 653.47 mg/100 g oil, respectively. Oleic acid methyl ester, 9-Octadecenoic acid methyl ester, and 9, 12-Octadecadienoic acid methyl ester were the predominant ingredients, with concentrations of 107.6, 243.42, and 256.77 mg/100 g oil, respectively. According to TEM and DLS examinations, BAO-Ag-NPs have a size of 38.20±2.5 nm and a negative zeta potential of -19.82 ± 0.30 mV, respectively. The LD50 of synthesized BAO-Ag-NPs is 2330 mg. On the other hand, BAO-Ag-NPs reduce myocardial necrosis by lowering increased BNP, cTnI, CK-MB, TC, TG, MDA, MMP2, TGF-β1, PGE2, and IL-6 levels. Furthermore, BAO-Ag-NPs inhibit the expression of ET-1, ICAM-1, and VCAM-1 genes. BAO-Ag-NPs given to ISO-treated rats enhance HDL-C, CAT, and GSH levels when compared to the ISO-treated group of rats. Histopathological findings suggested that BAO-Ag-NPs enhance cardiac function by increasing posterior wall thickness in heart tissues. BAO-Ag-NPs protect against AMI in vivo by regulating inflammation, excessive autophagy, and oxidative stress, as well as lowering apoptosis via suppression of the ET-1, ICAM-1, and VCAM-1 signaling pathways.


Determination of homozygous susceptible strain in Culex quinquefasciatus (Say), using single raft sib-selection method.
The standard laboratory strain was found to be heterozygous for susceptibility. Hence, an attempt was made to obtain a homozygous susceptible strain in Culex quinquefasciatus (Say) using single raft sib-selection method. Lab-bred females of Cx. quinquefasciatus from insectariums, Unit of Medical Entomology were used in the experiment. After blood feeding Cx. quinquefasciatus mosquitoes laid eggs in raft form, ten rafts selected randomly for the test. Each egg raft was introduced into a plastic tray from number one to number ten. Twenty-five third stage larvae from each tray were exposed to 17.5 microl from 500mg/l malathion in a paper cup label number 1 to number ten. In the bioassay, which had 100% mortality, the respective larva in that particular tray was bred to adult stage for the following generation. Less than 7days old female mosquitoes that emerged from F(0) were used in the test. The F(0) and the subsequent adult and larval stage generations were subjected to adult and larval bioassay. After selection for about 10 generations, a homozygous susceptible strain in Cx. quinquefasciatus was obtained.


The impact of VKORC1-1639 G>A polymorphism on the maintenance dose of oral anticoagulants for thromboembolic prophylaxis in North India: A pilot study.
The dose requirements for oral anticoagulants in thromboembolic events are influenced by promoter polymorphism in the VKORC1 gene. However, limited data are available on the influence of the polymorphism in various Indian populations. The present study aimed at determining the relationship between the VKORC1-1639 G>A genotypes and maintenance doses of oral anticoagulants for therapeutically stable INR values in patients taking Acitrom after valve replacement surgery. Fifty patients from the northern Indian region were genotyped for VKORC1-1639 G>A by polymerase chain reaction and restriction fragment length polymorphism. Means of the weight-normalized daily Acitrom dose were calculated for every patient. The VKORC1 1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity. The VKORC1-1639 G>A status can be indicative of establishing the therapeutic dose of oral anticoagulants in Indian patients.


Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses.
Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by both amnestic and non-amnestic clinical manifestations. It accounts for approximately 60-70% of all dementia cases worldwide. With the increasing number of AD patients, elucidating underlying mechanisms and developing corresponding interventional strategies are necessary. Hypotheses about AD such as amyloid cascade, Tau hyperphosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, cholinergic, and vascular hypotheses are not mutually exclusive, and all of them play a certain role in the development of AD. The amyloid cascade hypothesis is currently the most widely studied; however, other hypotheses are also gaining support. This article summarizes the recent evidence regarding major pathological hypotheses of AD and their potential interplay, as well as the strengths and weaknesses of each hypothesis and their implications for the development of effective treatments. This could stimulate further studies and promote the development of more effective therapeutic strategies for AD.


Novel rotaviruses in animals and man.
Novel (non-group A) rotaviruses have many of the morphological, biochemical and biological properties described originally for group A rotaviruses but they do not share the same group antigens. By negative-stain electron microscopy, novel rotaviruses have the characteristic rotavirus morphology, although with some novel rotaviruses the characteristic single- and double-shelled particles may not be readily apparent. Comparison of novel rotaviruses in serological tests has revealed the existence of at least six rotavirus serogroups, A to F, with the original rotaviruses belonging to group A. As with group A rotaviruses, viruses from different animal species, including man, can belong to the same serogroup. A further point of difference between novel and group A rotaviruses is their genome profiles, which lack the triplet of segments in the 7-8-9 region of group A rotaviruses. This is a useful diagnostic aid. Novel rotaviruses have been found in farm animals and man. They can cause enteritis experimentally and infect villus enterocytes. In chickens, turkeys, lambs and pigs the viruses and/or antibody to them are commonly found, in association with either clinical or subclinical infection. In humans one type of novel virus has emerged as a cause of severe diarrhoeal disease in adults. The possible reasons for the relatively recent discovery of the novel rotaviruses are discussed.


Study on the effects of microencapsulated Lactobacillus delbrueckii on the mouse intestinal flora.
To evaluate the protective effects of microencapsulation on Lactobacillus delbrueckii by random, parallel experimental design. Lincomycin hydrochloride-induced intestinal malfunction mouse model was successfully established; then the L. delbrueckii microcapsule was given to the mouse. The clinical behaviour, number of intestinal flora, mucous IgA content in small intestine, IgG and IL-2 level in peripheral blood were monitored. The histological sections were also prepared. The L. delbrueckii microcapsule could have more probiotic effects as indicated by higher bifidobacterium number in cecal contents. The sIgA content in microcapsule treated group was significantly higher than that in non-encapsulated L. delbrueckii treated group (p < 0.05). Intestine pathological damage of the L. delbrueckii microcapsule-treated group showed obvious restoration. The L. delbrueckii microcapsules could relieve the intestinal tissue pathological damage and play an important role in curing antibiotic-induced intestinal flora dysfunction.


Nonspecific cytotoxic cells in fish (Ictalurus punctatus). VI. Flow cytometric analysis.
Nonspecific cytotoxic cells (NCC) from channel catfish (Ictalurus punctatus) were enriched using flow cytometry (EPICS V, 753). Parameters of forward angle and 90 degrees light scatter were utilized to sort cytolytically functional populations of NCC. Fullbright (GR. II) 9.75 microns diameter fluorescent polystyrene microspheres were used for optical alignment. Cells obtained from the anterior kidney, spleen and peripheral blood were analyzed by one and/or two parameters of forward angle light scatter (FALS) and log integral 90 degrees light scatter (L90 degrees LS). Populations identified from FALS or L90 degrees LS histograms were sorted and cells were tested for cytotoxicity against NC-37 target cells. Anterior kidney contained at least four different sized populations of NCC. Spleen cells were sorted by FALS and four different populations of NCC detected. Peripheral blood contained little NCC activity. Enrichment of NCC activity from anterior kidney tissue was compared using Percoll density gradient separation and flow cytometry. Three to four fold higher cytotoxic activity was obtained from sorted cells compared to the population obtained from 45.5% Percoll. Additional experiments to determine the enrichment of sorted NCC were conducted by analyzing the number of enriched NCC required to kill an individual NC-37 target cell. Approximately 1.5-2.0 NCC could lyse a chromium-51 labelled target cell. These studies demonstrated that NCC could be enriched by size and granularity discrimination using flow cytometry. Effector:target cell ratios of 10:1 and lower produced significant lysis when sorted cells were analyzed.