[The authentication of modern Japanese acupuncture].
The Meiji government that modernized Japan decided the direction which adopted western medicine positively and eliminated Oriental medicine, and carried out the policy to inhibit acupuncture (1874). However, there was no concrete system until 1885, when the Ministry of Home Affairs issued a report to entrust the permission and superintendance of acupuncture to each prefecture. On the other hand, modern education for the blind was begun in various parts of the country in 1878, and acupuncture was adopted as a vocational course. The Rakuzenkai Blind School began Anma and acupuncture in 1881, but in 1885 acupuncture was removed from the curriculum and put under the direct control of the Ministry of Education. The principal of the school, Ryokichi Yatabe, had doubts about this and sent a question to Tokyo Imperial University. The answer to it (1887) was to recognize acupuncture, and this recognition became an admission of the revival of acupuncture in the course of blind education and the basis of the thought in legislation for modern Japanese acupuncture. There is a high possibilty that the reply to Yatabe was influenced by the article of Sansaku Okumura (1864-1912), a blind man in Kanazawa City, which appeared in the 157th issue of "Iji Shimbun" (1885).


Clinically occult prostate cancer cases may distort the effect of testosterone replacement therapy on risk of PCa.
Although prostate cancer (PCa) screening is conducted before testosterone replacement therapy (TRT), clinically occult PCa cases may exist. To evaluate whether the possible inclusion of occult PCa cases distorts the effect of TRT on risk of PCa, we followed 776 hypogonadal males (TRT = 400, non-TRT = 376) from a urology center in Germany from 2004 to 2016, with a mean follow-up period of 7 years. We assumed occult cases might take 1-2 years (latency period) to become clinically detectable after receiving TRT. We selected several latency periods (12/18/24 months) and compared the risk of PCa in the TRT and non-TRT group over the latency period, from the end of latency period till the end of follow-up, and over the whole follow-up time. Overall, 26 PCa cases occurred in the non-TRT group vs 9 cases in the TRT group. Within 18 months of follow-up, 9 cases occurred in the TRT group vs 0 cases in the non-TRT group; from the end of 18 months till the end of follow-up, 26 cases occurred in the non-TRT group vs 0 cases in the TRT group. The adjusted table showed seemingly adverse effects of TRT on PCa development within 18 months (p = 0.0301) and beneficial effects from the end of 18 months till the end of follow-up (p = 0.0069). Similar patterns were observed for 12 or 24 months as the latency period. TRT may make occult PCa cases detectable within early phase of treatment and present a beneficial effect in the long run. Future longitudinal studies are needed to confirm findings from our exploratory analyses.


Recent Advances in Understanding Delayed Photoluminescence in Colloidal Semiconductor Nanocrystals.
Colloidal semiconductor nanocrystals display remarkably bright, strongly size-dependent photoluminescence properties. Following photoexcitation of these materials, temporary charge carrier separation can occur where one or both charge carriers are trapped. Charge detrapping can reform the emissive state on long time scales up to seconds, causing delayed luminescence. This delayed luminescence has not yet been thoroughly explored, and appears to be closely associated with a phenomenon observed at the single particle level, i.e. photoluminescence intermittency (blinking). Here, some of our recent work on the delayed luminescence properties of nanocrystals of different chemical composition is reviewed. These results provide insight into the mechanism of carrier detrapping, and are discussed in the context of photoluminescence blinking.


Sensory optimization of crackers developed from high-quality cassava flour, starch, and prawn powder.
Crackers produced from high-quality cassava flour (HQCF), cassava starch, and prawn powder were optimized based on sensory preference testing. Ten different formulations of crackers were produced using mixture design. These were subjected to sensory evaluation using attributes such as taste, crispiness, puffiness, and acceptability on a 7-point hedonic scale. A mean score of 4.7, 5.6, 5.2, and 5.2 was obtained correspondingly for taste, crispiness, puffiness, and acceptability. Scores for these attributes indicated that the crackers were acceptable. Mixture regression models were used to generate contour plots for the sensory attributes and these were superimposed to obtain an optimal region, from where an optimum formulation was chosen. Verification of the optimal formulation with acceptability studies confirmed that the newly developed snack had a likeness score of 6.3 and was highly acceptable to consumers. The study demonstrates the suitability of HQCF in processing value added snack products.


Using mental practice in stroke rehabilitation: a framework.
Motor imagery and mental practice are getting increased attention in neurological rehabilitation. Several different mental practice intervention protocols have been used in studies on its effect on recovery in stroke rehabilitation. The content of the intervention protocols itself is rarely discussed or questioned. To give a practical framework of how mental practice could be integrated into therapy, drawing on available evidence and theory. The aim of the treatment programme described is to enhance both the patient's physical performance and their empowerment and self-determination. Based on evidence from sports rehabilitation and our own experiences the framework will eventually be evaluated in a randomized controlled trial. Five steps are described to teach and upgrade the patient's imagery technique: (1) assess mental capacity to learn imagery technique; (2) establish the nature of mental practice; (3) teach imagery technique; (4) embed and monitor imagery technique; (5) develop self-generated treatments. The description is not, however, a recipe that should be followed precisely. It leaves enough room to tailor the mental practice intervention to the specific individual possibilities, skills and needs of the patient in accordance with evidence-based practice. Different aspects of the described protocol are discussed and compared with experiences from sports and evidence available in rehabilitation.


A second-generation synthesis of the C1-C28 portion of the altohyrtins (spongistatins).
A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g of intermediate 57 has been produced using this improved route.


Positional Changes of the Ocular Organs During Craniofacial Development.
The present study aimed to describe the positional changes of the ocular organs during craniofacial development; moreover, we examined the relationships among the ocular organs and other internal structures. To do this, we traced the positions of the ocular organs in 56 human early fetal samples at different stages of development using high-resolution magnetic resonance imaging and phase-contrast X-ray computed tomography. The eyes were located on the lateral side in the ventral view at Carnegie stage (CS) 16, and then changed their positions medially during development. The eyes remained in the neurocranium until CS17. However, the eyes changed their positions medially and caudally in the viscerocranium after CS18. The positional relationship between the eyes and pituitary gland changed in the lateral view as development progressed. Specifically, they were close to each other at CS17, but moved apart during the later stages of development. These positional changes were also demonstrated quantitatively with morphometric analyses. Based on the present data, the positional changes of the eyes can be categorized into phases, as follows: Phase 1, dramatic positional changes (early fetal period until CS23); and Phase 2, mild positional changes (stabilized; early fetal period after CS23). Notably, all absolute lengths measured in the present study linearly increased as the crown-rump length increased irrespective of the phase, while features of the measured angles and ratios differentially changed in Phases 1 and 2. The present data may help improve our understanding of both the normal and abnormal development of the ocular organs and craniofacial area. Anat Rec, 300:2107-2114, 2017. © 2017 Wiley Periodicals, Inc.


A comparison of the efficacy of stimulus control for medicated and nonmedicated insomniacs.
A sample of 21 medicated and 20 nonmedicated insomniacs participated in a sleep medication withdrawal program that provided education about sleep medication and a gradual medication withdrawal schedule. Ten medicated participants received stimulus control treatment and the withdrawal program, and 11 medicated participants served as a control group that received only the withdrawal program. Half of the nonmedicated participants received stimulus control, and the remaining nonmedicated participants served as a wait-list control condition. Medicated participants significantly reduced sleep medication use without significant deterioration on sleep, anxiety, or depression measures from baseline to 8-week follow-up. Stimulus control participants, unlike control group participants, showed significant improvement at follow-up for total sleep time, sleep efficiency, and sleep quality. Stimulus control participants also reported less daytime sleepiness than control participants after treatment. Nonmedicated participants exhibited a more positive response to stimulus control than medicated participants.


Handpiece speed and postoperative outcomes in third molar surgery.
This study was performed to assess surgical outcomes when externally irrigated slow-speed surgical handpieces (30,000 rpm) were compared to externally irrigated high-speed handpieces (90,000 rpm) in the removal of impacted lower third molar teeth. One hundred patients with bilater ally impacted third molar s were enrolled in the study; 53 remained to completion. Each patient served as his/her own control. The experimental side was treated using a 30,000 rpm electric rotary drill incorporating irrigation, while the control side was treated using the same drill system, but with a 90,000 rpm handpiece. Drill speeds used were alternated between the right and left sides of patients to avoid bias introduced by the dominant hand of the surgeon. Patients were blinded to drill speed, and were asked to complete a standardized pain/swelling questionnaire for seven days immediately following surgery. Data was analyzed to determine differences in pain, swelling, and complications in relation to the drill type used. No statistically significant differences were found in degree of pain, swelling, or complications when the slower drill was compared to the high-speed instrument. The study suggests that there is no difference in postoperative outcome when impacted third molar teeth are removed with either slow- or high-speed instrumentation, and that the choice of the drill type should be determined solely by the preference of the operator.


Inhibition of phagocytic recognition of anti-D opsonized Rh D+ RBC by polymer-mediated immunocamouflage.
The Rh D antigen posed both a significant clinical risk and inventory supply issue in transfusion medicine. The successful development of the immunocamouflaged RBC has the potential to address both the risk of acute anti-D transfusion reactions and to improve D- blood inventory in geographic locations where D- blood is rare (e.g., China). The immunocamouflage of RBC was mediated by the covalent grafting of methoxy(polyethylene glycol) to the cell membrane thereby obscuring the D protein from the immune system. To determine the potential efficacy of mPEG-D+ RBC in D- recipients, anti-D alloantibodies from previously alloimmunized individuals were utilized. The effects of polymer chain size (2-30 kDa) and grafting concentration (0-4 mM) on antibody binding and erythrophagocytosis were determined using the clinically validated monocyte monolayer assay (MMA) and flow cytometry. The immunocamouflage of D was polymer size and grafting concentration dependent as determined using human anti-D alloantibodies (both pooled [RhoGAM] and single donors). Importantly, the 20 kDa polymer provided excellent immunocamouflage of D and reached a clinically significant level of protection, as measured by the MMA, at grafting concentrations of ≥1.5 mM. These findings further support the potential use of immunocamouflaged RBC to reduce the risk of acute transfusion reactions following administration of D+ blood to D- recipients in situations where D- units are unavailable or supply is geographically constrained.


Carnitine palmitoyltransferase I in liver of periparturient dairy cows: effects of prepartum intake, postpartum induction of ketosis, and periparturient disorders.
Thirty-five multiparous Holstein cows were used to determine the role of mitochondrial carnitine palmitoyltransferase I (CPT I) in liver on peripartal adaptations of fatty acid metabolism. From dry-off to parturition, cows were fed a diet at either ad libitum (n = 17) or restricted intake (RI, 80% of calculated requirements for net energy; n = 18). After parturition, all cows were fed a lactation diet. At 4 d in milk (DIM), cows underwent a physical examination and were classified as healthy (n = 15) or having at least one periparturient disorder (PD; n = 17). Cows in the healthy group were assigned to either a control (n = 6) group or a ketosis induction (KI; n = 9) group. Cows with periparturient disorders were assigned to a third (PDC; n = 17) group. Cows in control and PDC groups were fed for ad libitum intake. Cows in KI were fed at 50% of their respective intake at d 4 postpartum starting from 5 DIM and continuing to signs of clinical ketosis or until 14 DIM; cows then were returned to ad libitum intake. Liver was biopsied at -30 d, 1 d, at signs of clinical ketosis or 14 d, and 28 d relative to parturition. Mitochondria were isolated by differential centrifugation. Activity of CPT I was 5.4 and 7.6 nmol of palmitoylcarnitine formed per min/mg of protein for ad libitum and RI, respectively, at -30 DIM. Sensitivity of CPT I to its inhibitor, malonyl CoA, did not differ between ad libitum and RI cows. Differences in CPT I activity between ad libitum and RI were no longer significant at 1 DIM. Postpartum CPT I activity and malonyl CoA sensitivity at 1 DIM, onset of clinical ketosis or 14 DIM, and 28 DIM were not affected by prepartum intake (ad libitum vs. RI), postpartum health status (healthy vs. PD), or ketosis induction status (control vs. KI vs. PDC). Activity of CPT I was positively correlated with liver total lipid, liver triglyceride, liver triglyceride to glycogen ratio, and serum nonesterified fatty acids. Activity of CPT I and dry matter intake were not correlated. Prepartum intake affected prepartum CPT I activity but not malonyl CoA sensitivity. Neither induction of primary ketosis nor periparturient disorders greatly affected CPT I activity or sensitivity, which indicates that alterations of CPT I may not be a major factor in the etiology of primary ketosis or other periparturient disorders.


Three-stage sequential extraction procedure for metal partitioning in polluted soils and sediments.
The sequential extraction procedure proposed by the Standard, Measurements and Testing program "SM&T" of the European Union has been applied to evaluate the amounts of Cr, Cu, Mn, Ni, Pb and Zn, extracted at each stage and indirectly their mobility and bioavailability in soil and sediment samples from a polluted area. Analysis of the extracts was carried out by flame atomic absorption spectrometry (FAAS). No significant matrix interferences were found except for Cr in the acetic acid and hydroxylammonium chloride extracts, which required determination by the standard additions method. Both of soils and sediments studied show similar partitioning of Mn, Ni, Cu and Cr. Mn and Ni can be considered to have significant component bound to the acido-soluble fraction, whereas, Cr and Cu occur largely in the organic and residual phases. The partitioning of Pb and Zn was different between soil and sediment. In terms of mobility and bioavailability, in soils, Ni and Mn can be regarded as moderately available followed by a lower availability of Pb while Cu, Zn and Cr have a very limited availability. In sediments, a higher availability (short-medium term) of Mn and Zn was presumed followed by a lower availability of Ni and Pb, whereas, Cu and Cr, occurring largely in the organic and residual phases, were of very limited availability.


Pharmacokinetics, pharmacodynamics and clinical efficacy of ospemifene for the treatment of dyspareunia and genitourinary syndrome of menopause.
Ospemifene is a selective estrogen receptor modulator recently approved by the FDA for the treatment postmenopausal women experiencing moderate-to-severe dyspareunia and by the EMA for the treatment of moderate-to-severe symptomatic genitourinary syndrome of menopause (GSM) in women who are not suitable candidates for local vaginal estrogen therapy. This review offers an explanation of the pharmacodynamics and of the pharmacokinetics of ospemifene, and gives readers a complete overview of Phase II and III studies on the clinical efficacy, tolerability and safety of this agent in the setting of GSM. Ospemifene is efficacious for improving vaginal dryness or dyspareunia as the patient-identified most bothersome symptom, and Phase III clinical trials (4648 patients) have shown good efficacy in terms of improvement of objective and subjective signs and measures of GSM in postmenopausal women. Future studies with a long-term follow-up are required to better elucidate its safety profile. In particular, on the basis of preclinical and early clinical findings of antagonistic to neutral effect on breast tissue, more research is needed to assess the treatment with ospemifene in breast cancer survivors.


Urinary incontinence after radical prostatectomy: implications and urodynamics.
The purpose of this study was to evaluate urine loss, quality of life, and urodynamics in men who had urinary incontinence after radical prostatectomy and who were at least 12 months post surgery. Men from a previous study (N = 180) regarding quality of life and treatment of incontinence post prostatectomy were solicited. Twenty-one men were still incontinent 2 or more years post surgery; 16 agreed to further evaluation. The latter patients completed a 24-hour pad test, frequency/volume chart, quality-of-life questionnaire, and underwent video urodynamics. Median time from surgery was 22 months (14 to 33 months) and the mean urine loss over 24 hours was 164 g. Incontinence had an impact on quality of life, but men adjusted their lives and most would undergo radical prostatectomy again. Half of the subjects experiencing stress urinary incontinence on urodynamics also had a component of detrusor dysfunction (urge incontinence/decreased compliance). Quality of life was significantly affected by urinary incontinence, but most subjects would undergo radical prostatectomy again. Symptoms of stress urinary incontinence alone may not reflect the urodynamic diagnosis. Detrusor dysfunction should be considered in the etiology of incontinence after radical prostatectomy.


Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) is the major respiratory tract pathogen in infancy. Host-related differences in susceptibility to severe RSV infection suggest that genetic factors may play a role. In this study, a candidate-gene approach was used to study whether the surfactant protein D (SP-D) gene polymorphism associates with severe RSV infection. DNA samples from 84 infants hospitalized for the treatment of RSV bronchiolitis and 93 healthy controls were analyzed. The controls were matched with the cases on the basis of sex, hospital district, date of birth (+/-2 wk) and gestational age at birth (+/-2 wk). Three biallelic SP-D gene polymorphisms were genotyped. Significant differences were observed in the SP-D allele frequencies for amino acid 11 between the RSV infants and their matched controls. The frequency of the allele coding for Met 11 (p = 0.033) was increased in the severe RSV group. The frequency of the homozygous genotype Met/Met for amino acid 11 was increased in the RSV group relative to the controls, whereas the heterozygous genotype tended to be less frequent among the RSV cases than in the matched controls. Conditional logistic regression analysis was used to study whether the confounders, i.e. smoking and number of children in the family, influence the association between the homozygous SP-D genotype for methionine 11 and the risk of RSV bronchiolitis. The results further confirmed this association (p = 0.028). To our knowledge, the present report provides the first evidence of a specific gene associated with susceptibility to severe RSV infection.


Fedbatch design for periplasmic product retention in Escherichia coli.
The feed profile of glucose during fedbatch cultivation could be used to influence the retention of the periplasmic product ZZ-cutinase. An increased feed rate led to a higher production rate but also to an increased specific leakage, which reduced the periplasmic retention. Three growth rates: 0.3, 0.2 and 0.1 h(-1) where studied and resulted in 20, 9 and 6%, respectively, of the total ZZ-cutinase accumulating in the medium. It was also shown that leakage during fedbatch production of a Fab fragment was also influenced by the feed rate in a similar manner to ZZ-cutinase. If intracellular product accumulation is desired the advantage of a high productivity, resulting from a high substrate feed rate, is diminished because of a reduced product retention. Biochemical analysis revealed that the growth rate, resulting from a glucose limited feed, influenced the outer membrane protein compositions with respect to OmpF and LamB, whilst OmpA was largely unaffected. As the feed rate increased the amount of total outer membrane protein decreased. When ZZ-cutinase was produced there were further reductions in outer membrane protein accumulation, by 82, 100 and 22% for OmpF, LamB and OmpA, respectively, and the total reduction was almost 60% with a high product formation rate. We suggest that the reduced titre of the outer membrane proteins, OmpF and LamB, may have contributed to a reduced ability for the cell to retain recombinant protein secreted to the periplasm.


Plasmodium knowlesi in human, Indonesian Borneo.
Plasmodium knowlesi is now established as the fifth Plasmodium species to cause malaria in humans. We describe a case of P. knowlesi infection acquired in Indonesian Borneo that was imported into Australia. Clinicians need to consider this diagnosis in a patient who has acquired malaria in forest areas of Southeast Asia.


Spatial regulation of neuronal gene expression in response to nerve growth factor.
To examine the cellular mechanisms whereby distally derived growth factors regulate nuclear responses in neurons, we have utilized compartmented cultures of sympathetic neurons to examine the regulation of two nerve growth factor (NGF)-inducible genes, tyrosine hydroxylase (TH) and p75 neurotrophin receptor (p75NTR). These studies demonstrate that NGF can signal retrogradely to mediate the induction of TH and p75NTR mRNAs. However, quantitative differences occurred as a function of the spatial localization of NGF exposure; application of NGF to cell bodies and proximal axons elicited peak levels of neuronal gene expression that were two- to threefold higher than when NGF was applied to distal axons alone. Furthermore, neurons responding maximally to NGF on distal axons were still able to respond to NGF administered to cell bodies and proximal axons. Biochemical analysis indicated that this difference in responsiveness was not due to differences in the number of TrkA/NGF receptors in the two compartments. Thus, although NGF signals retrogradely to mediate nuclear responses, the magnitude of these responses differs as a function of the spatial location of the activated NGF receptor:ligand complex. Moreover, these data suggest that neurons may be able to respond to a second cellular source of neurotrophins, even when target-derived neurotrophins are not limiting.


The management of complicated glaucoma.
Complicated glaucomas present considerable diagnostic and management challenges. Response to treatment can be unpredictable or reduced compared with other glaucomas. However, target intraocular pressure and preservation of vision may be achieved with selected medical, laser and surgical treatment. The evidence for such treatment is expanding and consequently affords clinicians a better understanding of established and novel techniques. Herein we review the mechanisms involved in the development of complicated glaucoma and the current evidence supporting its management.


Electronic and Tunneling Predissociations in the 2pπC1Πu±(υ = 19) and 3pπD1Πu±(υ = 4, 5) States of D2 Studied by a Combination of XUV Laser and Velocity Map Imaging.
The predissociation mechanism of D2 near the threshold for the production of the D(2s, 2p) fragments has been studied by measuring the fragment yield spectra, fragment velocity map images, and fragment branching ratios D(2s)/(D(2s) + D(2p)) using a combination of XUV laser and velocity map imaging. The predissociation dynamics of the 2pπC1Πu±(υ = 19) and 3pπD1Πu±(υ = 4,5) states were studied. The 2pπC1Πu±(υ = 19) state is a bound state due to a shallow barrier. For the R(0) transition to the 2pπC1Πu+(υ = 19) state, the experimental results suggest that the predissociation occurs via three channels with decreasing importance: l-uncoupling with the 2pσB1Σu+ state, tunneling, and l-uncoupling with the 3pσB'1Σu+ state. For the R(1) transition to the 2pπC1Πu+(υ = 19) state, the first channel plays the dominant role. For the Q(1) transition to the 2pπC1Πu-(υ = 19) state, the predissociation occurs via tunneling as required by symmetry. For the predissociation of the 3pπD1Πu+(υ = 4,5) states, the experimental data confirm the earlier results indicating that the main perturbing state is 3pσB'1Σu+. The Beutler-Fano profiles and the associated spectroscopic parameters for the various predissociations have also been obtained. The measured Fano-parameters q for the P- and R-branches of the 3pπD1Πu+ state are found to have opposite signs, and their relationships are in agreement with a formula derived from the Fano equation. Rotationally resolved Beutler-Fano profiles were measured for the P(2) and P(3) lines.


Benzimidazole and related ligands for Cu-catalyzed azide-alkyne cycloaddition.
Tris(2-benzimidazolylmethyl)amines have been found to be superior accelerating ligands for the copper(I)-catalyzed azide-alkyne cycloaddition reaction. Candidates bearing different benzimidazole N-substituents as well as benzothiazole and pyridyl ligand arms were evaluated by absolute rate measurements under relatively dilute conditions by aliquot quenching kinetics and by relative rate measurements under concentrated conditions by reaction calorimetry. Benzimidazole-based ligands with pendant alkylcarboxylate arms proved to be advantageous in the latter case. The catalyst system was shown to involve more than one active species, providing a complex response to changes in pH and buffer salts and the persistence of high catalytic rate in the presence of high concentrations of coordinating ligands. The water-soluble ligand (BimC4A)3 was found to be especially convenient for the rapid and high-yielding synthesis of several functionalized triazoles with 0.01-0.5 mol % Cu.


Heterogeneous Epoxide Carbonylation by Cooperative Ion-Pair Catalysis in Co(CO)4--Incorporated Cr-MIL-101.
Despite the commercial desirability of epoxide carbonylation to β-lactones, the reliance of this process on homogeneous catalysts makes its industrial application challenging. Here we report the preparation and use of a Co(CO)4--incorporated Cr-MIL-101 (Co(CO)4⊂Cr-MIL-101, Cr-MIL-101 = Cr3O(BDC)3F, H2BDC = 1,4-benzenedicarboxylic acid) heterogeneous catalyst for the ring-expansion carbonylation of epoxides, whose activity, selectivity, and substrate scope are on par with those of the reported homogeneous catalysts. We ascribe the observed performance to the unique cooperativity between the postsynthetically introduced Co(CO)4- and the site-isolated Lewis acidic Cr(III) centers in the metal-organic framework (MOF). The heterogeneous nature of Co(CO)4⊂Cr-MIL-101 allows the first demonstration of gas-phase continuous-flow production of β-lactones from epoxides, attesting to the potential applicability of the heterogeneous epoxide carbonylation strategy.


Fertilization of zona-drilled mouse oocytes treated with a monoclonal antibody to the zona glycoprotein, ZP3.
Opening a small aperture in the zona pellucida of mouse oocytes by using micromanipulation and a stream of acidified Tyrode's solution (zona drilling) improved the efficiency of in vitro fertilization at low sperm concentrations without adversely affecting development to the blastocyst stage. Zona drilling also permitted in vitro fertilization and development when sperm penetration through the zona was blocked by a monoclonal antibody to the protein core of the zona glycoprotein, ZP3. These results provide a direct demonstration that sperm entry occurs through the aperture and also suggest that zona drilling of human oocytes may offer a therapeutic approach when autoantibodies to the zona pellucida are suspected as a cause of infertility.


Reflectance Measurements from Aerial and Proximal Sensors Provide Similar Precision in Predicting the Rice Yield Response to Mid-Season N Applications.
Accurately detecting nitrogen (N) deficiency and determining the need for additional N fertilizer is a key challenge to achieving precise N management in many crops, including rice (Oryza sativa L.). Many remotely sensed vegetation indices (VIs) have shown promise in this regard; however, it is not well-known if VIs measured from different sensors can be used interchangeably. The objective of this study was to quantitatively test and compare the ability of VIs measured from an aerial and proximal sensor to predict the crop yield response to top-dress N fertilizer in rice. Nitrogen fertilizer response trials were established across two years (six site-years) throughout the Sacramento Valley rice-growing region of California. At panicle initiation (PI), unmanned aircraft system (UAS) Normalized Difference Red-Edge Index (NDREUAS) and GreenSeeker (GS) Normalized Difference Vegetation Index (NDVIGS) were measured and expressed as a sufficiency index (SI) (VI of N treatment divided by VI of adjacent N-enriched area). Following reflectance measurements, each plot was split into subplots with and without top-dress N fertilizer. All metrics evaluated in this study indicated that both NDREUAS and NDVIGS performed similarly with respect to predicting the rice yield response to top-dress N at PI. Utilizing SI measurements prior to top-dress N fertilizer application resulted in a 113% and 69% increase (for NDREUAS and NDVIGS, respectively) in the precision of the rice yield response differentiation compared to the effect of applying top-dress N without SI information considered. When the SI measured via NDREUAS and NDVIGS at PI was ≤0.97 and 0.96, top-dress N applications resulted in a significant (p < 0.05) increase in crop yield of 0.19 and 0.21 Mg ha-1, respectively. These results indicate that both aerial NDREUAS and proximal NDVIGS have the potential to accurately predict the rice yield response to PI top-dress N fertilizer in this system and could serve as the basis for developing a decision support tool for farmers that could potentially inform better N management and improve N use efficiency.


The ultrastructural features of the infundibulum of the green iguana, Iguana iguana.
The purpose of this study is to describe, in detail, the ultrastructure of the infundibulum of the sexually mature and active female green iguana, Iguana iguana. The infundibulum of five iguanas was remarkably distinct from the uterus, and was also clearly demarcated into cranial (expanded v-shaped) and caudal (tubular) divisions. Tissue samples obtained from five portions (three from the cranial division and two from the caudal division) of the infundibulum were processed conventionally for light and electron microscopy. The epithelial lining of the most anterior, middle, and posterior, parts of the cranial division displayed nonciliated cells predominantly, and occasionally ciliated cells. The numerous secretory granules in nonciliated type 1 cell found in the fimbrial aspect of the infundibulum were homogenous and deeply electron-dense, but those in the other two regions were variants of this cell type because they contained variably electron-dense secretory granules. Two main types of nonciliated cells (type 2 and its variant, type 3, as well as type 4) occurred in the epithelial lining of the caudal division of the infundibulum, but they, clearly, showed no dense secretory granules. Whereas the nonciliated type 2 cell and its variant (type 3 cell) contained large glycogen deposits, the type 4 cell lacked these deposits but its apical part contained large lipid-like droplets and, remarkably, blebbed into the duct lumen. The nonciliated cells lining the mucosal tubular glands contained highly electron-dense secretory granules, which were similar to those found in the nonciliated type 1 cell in the epithelial lining of the fimbrial part of the cranial division of the infundibulum.


Light cigarette smoking and vascular function.
The present study was undertaken to test the hypothesis that smoking induces peripheral endothelial dysfunction and altered function in central conduit arteries. A total of 22 healthy volunteers (10 women and 12 men; mean age 25.3 +/- 5.8 years) were included. At baseline, brachial artery flowmediated dilatation (FMD), aortic stiffness index (ASI), aortic distensibility (AoD), and aortic elastic modulus (AoEM) of all subjects were measured. On the 2nd day, the subjects were assigned to smoke either 1 light (0.6 mg of nicotine, 8 mg of tar, and 9 mg of carbon monoxide) or 1 regular cigarette (0.9 mg of nicotine, 12 mg of tar, and 12 mg of carbon monoxide) and the measurements were repeated for all subjects 20 minutes following smoking. After 15 days, the subjects were assigned to smoke 1 cigarette of the type that was not smoked on the 2nd day, and the same measurements were performed 20 minutes after smoking. In response to smoking 1 light cigarette, FMD values declined from 15.0 +/- 6.8% to 9.1 +/- 2.9% (P = 0.002). After smoking 1 regular cigarette, FMD values declined from 15.0 +/- 6.8% to 9.4 +/- 4.8% (P= 0.002). Aortic elasticity and left ventricular diastolic functions (LVDF) were significantly impaired by both types of cigarettes. Smoking light cigarettes has similar acute detrimental effects on FMD, LVDF, ASI, AoD, and AoEM as regular cigarettes.


Acute pancreatitis is associated with Ser608Leu iNOS polymorphism.
Acute pancreatitis is an initially localized inflammation of the pancreatic gland. The precise mechanisms by which aetiological factors induce acute pancreatitis are not yet known, but when initiated, common inflammatory pathways seem to be involved, with cytokines being their components of major importance. The inducible nitric oxide synthase gene (iNOS) encodes an enzyme involved in the pathway of reactive oxygen species and induced in response to infection, cytokines. iNOS is capable of generating large quantities of nitric oxide produced during inflammation. The objective of this study was to investigate the association between acute pancreatitis risk and iNOS polymorphisms. The studied single-nucleotide polymorphisms (SNPs) were Ser608Leu, resulting in an amino acid substitution, and 1173C/T and 954G/C, both in the gene promoter region that is linked to increased enzyme expression, leading to higher NO production. The genotypes for the three SNPs were determined in 93 patients with acute pancreatitis and 60 controls without pancreatitis or cancer that were matched for age and gender. Data analysis was done by conditional logistic regression. It was found that the Ser608Leu polymorphism was more frequent among cases with acute pancreatitis compared to controls (OR = 2.88; 95% CI: 1.49-5.57; P = 0.002), although no individually statistically significant associations for the other SNPs studied were detected. We suggest that iNOS Ser608Leu can be used as a marker to define the risk of acute pancreatitis.


Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.
Constitutional mismatch repair deficiency (CMMR-D) syndrome is a rare inherited childhood cancer predisposition caused by biallelic germline mutations in one of the four mismatch repair (MMR)-genes, MLH1, MSH2, MSH6 or PMS2. Owing to a wide tumor spectrum, the lack of specific clinical features and the overlap with other cancer predisposing syndromes, diagnosis of CMMR-D is often delayed in pediatric cancer patients. Here, we report of three new CMMR-D patients all of whom developed more than one malignancy. The common finding in these three patients is agenesis of the corpus callosum (ACC). Gray matter heterotopia is present in two patients. One of the 57 previously reported CMMR-D patients with brain tumors (therefore all likely had cerebral imaging) also had ACC. With the present report the prevalence of cerebral malformations is at least 4/60 (6.6%). This number is well above the population birth prevalence of 0.09-0.36 live births with these cerebral malformations, suggesting that ACC and heterotopia are features of CMMR-D. Therefore, the presence of cerebral malformations in pediatric cancer patients should alert to the possible diagnosis of CMMR-D. ACC and gray matter heterotopia are the first congenital malformations described to occur at higher frequency in CMMR-D patients than in the general population. Further systematic evaluations of CMMR-D patients are needed to identify possible other malformations associated with this syndrome.


Accuracy of 99mTc-Hydroxymethylene diphosphonate scintigraphy for diagnosis of transthyretin cardiac amyloidosis.
Either 99mTechnetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy plays a relevant role in diagnosing transthyretin cardiac amyloidosis (CA), and labeled radiotracers have been extensively studied in diagnosing CA. Few studies have analyzed and validated 99mTc-Hydroxymethylene diphosphonate (Tc-HMDP). Our aim was to validate the diagnostic accuracy of Tc-HMDP total-body scintigraphy in a cohort of patients with biopsy-proven transthyretin CA. We retrospectively evaluated all patients undergoing 99mTc-HMDP total-body scintigraphy, in adjunct to a comprehensive diagnostic work-up for suspected CA. Sixty-five patients were finally diagnosed with CA, while it was excluded in 20 subjects with left ventricular hypertrophy of various etiologies. Twenty-six patients had AL-CA, 39 had TTR CA (16 TTRm, 23 TTRwt). At Tc-HMDP scintigraphy, 2 AL patients showed a Perugini score grade 1 heart uptake, while 24 showed no uptake. All TTR patients showed Tc-HMDP uptake, with three patients showing a Perugini score grade 1, 16 grade 2, and 20 grade 3, respectively. No uptake was observed in patients with left ventricular hypertrophy. A positive Tc-HMDP scintigraphy showed a 100% sensitivity and a 96% specificity for TTR CA identification. Tc-HMDP scintigraphy is as accurate as Tc-DPD or Tc-PYP, and may therefore de facto be considered a valuable tool for the diagnosis of TTR CA.


[Occupational risks and repetitive strain injuries in the Italian legislation].
Based on the experience gained from several criminal proceedings handled by the Public Prosecutor's Office in Turin, the author presents and discusses the Italian legislation covering the prevention of musculo-skeletal pathologies of the upper limbs in the workplace. In particular, the author examines the obligations associated with issuing medical reports on such disorders, and focusses attention on the obligations of the employer with respect to prevention (i.e. technical, organisational and procedural measures), monitoring employee health and the provision of training and information for employees in the light of both existing legislation (Italian Civil Code, DPR 303/56 and DPR 1124/65) and more recent regulations (D. Lgs. 626/94).


Antimicrobial susceptibility testing of rapidly growing mycobacteria isolated in Japan.
Difficult-to-treat infections caused by rapidly growing mycobacteria (RGM) are increasingly observed in clinical settings. However, studies on antimicrobial susceptibilities and effective treatments against RGM in Japan are limited. We conducted susceptibility testing of potential antimicrobial agents, including tigecycline and tebipenem, against RGM. Clinical RGM isolates were collected from a university hospital in Japan between December 2010 and August 2013. They were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the sequencing of 16S rRNA, rpoB, and hsp65 genes. The samples were utilized for susceptibility testing using 16 antimicrobials, with frozen broth microdilution panels. Forty-two isolates were obtained: 13, Mycobacterium abscessus complex; 12, Mycobacterium chelonae; 9, Mycobacterium fortuitum; and 8, M. fortuitum group species other than M. fortuitum. Different antimicrobial susceptibility patterns were observed between RGM species. Clarithromycin-susceptible strain rates were determined to be 0, 62, and 100% for M. fortuitum, M. abscessus complex, and M. chelonae, respectively. M. abscessus complex (100%) and >80% M. chelonae isolates were non-susceptible, while 100% M. fortuitum group isolates were susceptible to moxifloxacin. Linezolid showed good activity against 77% M. abscessus complex, 89% M. fortuitum, and 100% M. chelonae isolates. Regardless of species, all tested isolates were inhibited by tigecycline at very low minimal inhibitory concentrations (MICs) of ≤0.5 μg/mL. MICs of tebipenem, an oral carbapenem, were ≤4 μg/mL against all M. fortuitum group isolates. Our study demonstrates the importance of correct identification and antimicrobial susceptibility testing, including the testing of potential new agents, in the management of RGM infections.


Assessment of the mutagenic, recombinogenic, and carcinogenic potential of amphotericin B in somatic cells of Drosophila melanogaster.
Amphotericin B (AmB) is an antifungal antibiotic extracted from Streptomyces nodosus. Its fungicidal activity depends primarily on its binding to the sterol group that is present in fungal membranes. In view of the toxicity of this drug, the purpose of this study was to evaluate its mutagenic, carcinogenic, and recombinogenic activity, based on the wing somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts) applied to Drosophila melanogaster. Larvae were chronically treated with different concentrations of AmB (0.01, 0.02, and 0.04 mg/mL). The results revealed that AmB is a promutagen exhibiting increase in the number of spots on individuals from high bioactivation (HB) cross with a high level of cytochrome P450. The results also indicate that the main genotoxic event induced by AmB is recombinogenicity. Homologous recombination can act as a determinant at different stages of carcinogenesis. For verification of carcinogenic potential of this compound, larvae from the wts/mwh and wts/ORR, flr3 were treated with the same three AmB concentrations used in the SMART assay. The results did not provide evidence that AmB has carcinogenic potential in wts/mwh individuals. However, individuals from wts/ORR, flr3 developed tumors at the highest concentration tested.


[Diversified treatments of Tinea unguium].
Antifungal agents and therapeutic approaches for tinea unguium have been increasing in number. Itraconazole, terbinafine and fluconazole were developed in the 1990s, and many useful methods with them for tinea unguium have been reported, including pulse therapy and short duration therapy. There have been many reports of not only oral treatments but also contrived topical treatments, in most of which improvement rates were high. However, each treatment has had some drawbacks and did not seem to gain the complete compliance of patients. Many patients dropped out, still having affected nails. It seems important to us to understand thoroughly the merits and demerits of each diversified treatment for tinea unguium and to provide the preferential treatment for each patient.


Preliminary observations on the efficacy of a recombinant multistage Plasmodium falciparum vaccine in Aotus nancymai monkeys.
A vaccine trial was conducted to determine the efficacy of a multicomponent candidate vaccine, FALVAC-1, against Plasmodium falciparum in Aotus nancymai monkeys. After two immunizations, animals were challenged intravenously with parasites of the Vietnam Oak Knoll (FVO) strain of P. falciparum. The primary outcome was to determine the protective response of the monkeys to immunization with the FALVAC-1 antigen produced in baculovirus when combined with different adjuvants (alum, QS-21, ASO2a, CRL1005/oil, and CRL1005/saline) as compared with FALVAC-1 with FCA/FIA and antigen alone. When compared with the monkeys immunized with FALVAC-1 alone, FALVAC-1 with FCA/FIA reduced the mean parasite count (to Day 11), reduced the mean accumulated parasitemia (through Day 11), and extended the number of days to treatment. None of the other 5 antigen-adjuvant combinations were able to provide discernable levels of protection based on log(parasitemia) and log(cumulative parasitemia) to Day 11.


The Application and Teaching Value of a Ventricular Septal Defect Canine Model Established by Transcatheter Puncture.
This study aimed to improve and further explore a ventricular septal defect (VSD) canine model on the basis of the transcatheter puncture method and to evaluate its application and teaching value.In order to lessen the complications of VSD closure, it is necessary to improve the currently available treatment devices using appropriate animal models.In this study, we used 16 healthy adult canines as our models. After anesthesia, the VSD puncture was performed, followed by balloon dilatation of the perforation. VSD was confirmed by angiography. The venous-artery orbit was established, and the VSD was then closed once the catheter and occluder were across the defect.Of the experimental canines, 14 of the 16 canines were successfully modeled, giving a success rate of 87.5%. The canines underwent an immediate creation of a venous-artery orbit for teaching practice and were implanted with an occluder during the procedure. After 4 weeks, 13 canines survived. As per our findings, most VSD types established by the puncture were perimembranous (10 of 13, 77%).The current model has a high success rate. The model can not only avoid the risk of infection and hemodynamic disorders associated with an open thoracotomy, but can also be effectively used in evaluating the impact of occluders. It can also directly measure the parameters of the devices during the procedure, thus having a very high experimental and teaching value.


[Psoriasis therapy with fumaric acid and fumaric acid esters].
Fumaric acid may not be regarded as an antipsoriatic drug. Beneficial effects on psoriatic lesions may be explained by secondary changes such as the acidification of gastric juice in cases of anacidity or hypacidity . Monoethylfumarate exerts true antipsoriatic activities but is by far too toxic for clinical use. Experimental investigations have confirmed an inhibitory action of the above-mentioned fumarate on nucleic acid synthesis and protein synthesis of PHA-stimulated human lymphocytes.


Habitat-associated skew of clone abundance in the Pseudomonas aeruginosa population.
The population structure of the cosmopolitan Pseudomonas aeruginosa was investigated by genotyping 2921 isolates from 1448 independent habitats with a custom-made 58 binary marker microarray. Of 323 identified clone types, 109 clones made up 82% of the population. The 20 most frequent clones had an absolute share of 44% indicating that the P. aeruginosa population is dominated by few epidemic clonal complexes. The frequency distribution of common clones was different between inanimate habitats and human niches. The three most abundant clones in the environment were rare among isolates from human infection. Conversely, disease-associated isolates either belonged to ubiquitous clones such as C and PA14 or to clones that were uncommon in the environment. The P. aeruginosa population consists of major clones that are just as versatile in their habitat and geographic origin as the whole species and of minor clones with preference for a peculiar niche.


Itch and atopic dermatitis: clinical and experimental studies.
The aims of the study were to develop and evaluate methods for quantitative measurement of itch, to investigate the perception of itch in patients with atopic dermatitis (AD), and to measure itch in such patients during treatment with H1-receptor antagonists or cyclosporin A, thereby exploring possible mechanisms in the pathogenesis of itch in AD. In a double-blind, randomized, placebo-controlled, cross-over study of 30 AD patients using a potent, topical, antipruritic corticosteroid, two methods for measuring itch both successfully detected the itch-relieving effect of the corticosteroid. The two methods comprised new portable data-loggers (Pain-Track) for continuous recording of itch, and conventional visual analogue scale (VAS) forms for retrospective recording. The main advantages of the Pain-Track method are possibilities for frequent sampling, surveillance of compliance, and analysis of a large amount of data. Induction and measurement of experimental histamine-induced itch were studied in 38 healthy subjects. It was shown that pruritic stimuli should be presented in a random order so as to avoid systematic errors in the perception of itch. Two rating scales, a seven-stepped non-verbal scale on a Pain-Track logger, and a 100-mm VAS on a potentiometer, were found valid for continuous recording of itch. The perception of experimental itch was studied in 32 AD patients and 32 healthy controls. The itch responses provoked by wool fibres were significantly stronger in AD patients than in controls, whereas the histamine-induced dose-response curves for itch did not differ significantly between the two groups, who discriminated equally well between weak and strong histamine stimuli. No increased skin mast cell releasability was shown in vivo to compound 48/80 in AD patients. Their itch responses to the different pruritic stimuli did not correlate with clinical itch intensity, eczema score or serum IgE-level. In a double-blind, randomized, placebo-controlled, cross-over study of 25 AD patients, the effect on clinical itch of a sedative (clemastine) and of a non-sedative (terfenadine) antihistamine did not differ from that of placebo, although both drugs had a pronounced H1-receptor-antagonizing effect in the skin and clemastine was significantly sedative. These findings support the view that histamine is not the major pruritogen in AD, and that sedation is not necessarily associated with itch relief. In a double-blind, randomized, placebo-controlled, cross-over study of 10 AD patients, 10 days' treatment with cyclosporin A (CSA), 5 mg/kg/day, significantly reduced itch intensity, eczema score and the number of peripheral blood eosinophils.(ABSTRACT TRUNCATED AT 400 WORDS)


The perspectives of nursing students regarding the incorporation of African traditional indigenous knowledge in the curriculum.
South Africa was caught off guard by the student unrest in 2015 and 2016. This unrest was named the #fees must fall campaign. During this campaign, students raised the issue of decolonisation of the curriculum, challenging the higher education fraternity and the academic community. This was based on the fact that the existing curriculum has inadequate content on African traditional indigenous knowledge (ATIK), and continues to use the Western approach to address the needs of a multicultural, multiracial and multi-ethnic societies. Institutions responded by initiating dialogues regarding decolonisation of the curriculum in senates, scholars and between different health professional bodies. This article aimed to explore and describe the perspectives of nursing students regarding incorporating ATIK into the curriculum. Using a participatory transformative approach, researchers and participants worked collaboratively to inform social change. Participants comprised nursing students. The academics, traditional health practitioners, indigenous knowledge holders and primary health care nurses formed the panellists. Data were collected through one communal dialogue workshop, which lasted for 8 hours, tea and lunch included. Data were analysed thematically. Students' perspectives emerged strongly as four themes, namely, politics of identity, displacement and distortion, curriculum content and institutional resistance. Students expressed that the current education system results in an identity crisis. The existing curriculum does not adequately convey an understanding of ATIK; it is displaced and distorted. Nursing science has great potential to incorporate the wealth of ATIK into its curriculum. In spite of a vibrant and rich cultural heritage, the ATIK specific to nursing sciences still needs to be incorporated into the existing curriculum in a responsive and relevant manner.


Self-assembled synthesis of hierarchical Zn2GeO4 core-shell microspheres with enhanced photocatalytic activity.
Hierarchically spherical materials with a core-shell structure are of special interest for a variety of promising applications. Although some advanced synthetic methods have been reported, the development of a facile strategy to fabricate hierarchically spherical materials with a core-shell structure is still desirable. Herein, hierarchical Zn2GeO4 core-shell microspheres, with stacked nanoparticles at the core and well-aligned rods at the shell, are successfully synthesized through a triethylenetetramine (TETA)-induced self-assembly route. They exhibit relatively high photocatalytic activity and stability towards degradation of organic pollutants under UV light irradiation. In addition, other diverse hierarchical Zn2GeO4 macrocrystals can be successfully prepared by rationally tuning the reaction parameters. The present synthetic strategy may allow access to fabricating other multifunctional materials with special artistical morphologies.


[The mechanism of oxymyoglobin oxidation catalyzed by ferrocyanide ions: chemically modified and mutant sperm whale myoglobins].
A comparative study of the rate of ferrocyanide-catalyzed oxidation of native sperm whale MbO2, its chemically modified derivative in which all accessible His residues are alkylated by sodium bromoacetate, (CM-MbO2), and mutant sperm whale MbO2 with His119 replaced by Asp residiue, [MbO2(His119-->Asp)] was carried out. The influence of pH, ionic strength, and [Fe(CN)6]4- concentration on the oxidation rate was investigated, as well as the effect of complexing MbO2 with redox-inactive Zn2+ ion, which, at the equimolar Zn2+ concentration, forms a stable complex with His119(GH1) on the protein surface. It was shown that the mechanism of the catalysis involves specific binding of [Fe(CN)6]4- to the protein at the His119(GH1) region, which is in agreement with a large positive electrostatic potential and the presence at this site of Mb of a cavity large enough to accommodate [Fe(CN)6]4- anion. The protonation of nearby His113 and His116 residiues (especially of the latter) plays a very important role in the catalysis, promoting the fast oxidation of bound [Fe(CN)6]4- by dissolved oxygen. Only the presence of these both necessary conditions in MbO2 structure provides its effective oxydation catalyzed by ferrocyanide.


Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis.
Multiple sclerosis (MS) patients of an inpatient rehabilitation program have been randomly assigned to an exercise training (MS-ET) or nontraining group (MS-NI). Before and after 4 weeks of aerobic exercise training, a graded maximal exercise test with measurement of gas exchange and a lung function test was administered to all 26 patients fulfilling the inclusion criteria. Activity level, fatigue and health perception were measured by means of questionnaires. Twenty-six healthy persons served as control group and were matched in respect of age, gender and activity level. Training intervention consisted of 5x30 min sessions per week of bicycle exercise with individualised intensity. Compared with baseline, the MS training group demonstrated a significant rightward placement of the aerobic threshold (AT) (VO2+13%; work rate [WR])+11%), an improvement of health perception (vitality+46%; social interaction+36%), an increase of activity level (+17%) and a tendency to less fatigue. No changes were observed for the MS-NI group and the control groups. Maximal aerobic capacity and lung function were not changed by either training or nontraining in all four groups. Overall compliance to the training program was quite low (65%), whereas incidence of symptom exacerbation by physical activity has been lower than expected (6%).


[The problem of hygienic standardization of commercial electric and magnetic fields in Russia and other countries].
Review of standards show that many countries still have no hygienic regulations concerning the electric and magnetic fields of commercial frequencies. National standards have been developed by only a few countries. In a number of countries guidelines for protection from the electric fields have been elaborated with the magnetic component disregarded. National standards show a significant difference, too. In most cases the maximum admissible levels are approximate and ignore potential synergetic biological effects of the agents; many of them do not set an adequate coefficient of the hygienic margin or foresee possible carcinogenous risk.


Identification of interacting neural populations: methods and statistical considerations.
As improved recording technologies have created new opportunities for neurophysiological investigation, emphasis has shifted from individual neurons to multiple populations that form circuits, and it has become important to provide evidence of cross-population coordinated activity. We review various methods for doing so, placing them in six major categories while avoiding technical descriptions and instead focusing on high-level motivations and concerns. Our aim is to indicate what the methods can achieve and the circumstances under which they are likely to succeed. Toward this end, we include a discussion of four cross-cutting issues: the definition of neural populations, trial-to-trial variability and Poisson-like noise, time-varying dynamics, and causality.


Quasi 3D ECE imaging system for study of MHD instabilities in KSTAR.
A second electron cyclotron emission imaging (ECEI) system has been installed on the KSTAR tokamak, toroidally separated by 1/16th of the torus from the first ECEI system. For the first time, the dynamical evolutions of MHD instabilities from the plasma core to the edge have been visualized in quasi-3D for a wide range of the KSTAR operation (B0 = 1.7∼3.5 T). This flexible diagnostic capability has been realized by substantial improvements in large-aperture quasi-optical microwave components including the development of broad-band polarization rotators for imaging of the fundamental ordinary ECE as well as the usual 2nd harmonic extraordinary ECE.


BRAIN MITOCHONDRIA. II. THE RELATIONSHIP OF BRAIN MITOCHONDRIA TO GLYCOLYSIS.
A mitochondrial fraction prepared from calf brain cortex possessed negligible glycolytic activity in the absence of the enzymes of the high speed supernatant fraction. When mitochondria were added to a supernatant system supplemented with optimal amounts of crystalline hexokinase, a 20 per cent stimulation of glycolysis was observed. The supernatant fraction produced minimal amounts of lactate in the absence of exogenous hexokinase; the addition of mitochondria doubled the lactate production. The substitution of glycolytic intermediates for glucose as substrates as well as the addition of exogenous glycolytic enzymes to the supernatant fraction or supernatant fraction plus mitochondria indicated that the mitochondria contributed mainly hexokinase and phosphofructokinase. By direct assay of all of the enzymes of the glycolytic pathway, only hexokinase and phosphofructokinase were shown to be concentrated in the mitochondrial fraction. All other glycolytic enzymes were found to exhibit higher total and specific activities in the supernatant fraction.


Dietary nucleotides: effects on cell proliferation following partial hepatectomy in rats fed NIH-31, AIN-76A, or folate/methyl-deficient diets.
The requirement of a number of tissues for dietary nucleotides could explain some of the differences observed in animals fed natural ingredient diets vs. those fed purified diets lacking a source of dietary nucleotides. Lack of dietary nucleotides is exacerbated in animals fed folate- or methyl-deficient semipurified diets, in which both salvage and folate-dependent de novo synthetic pathways are diminished. We examined hepatocyte proliferation following partial hepatectomy in weanling male Fischer-344 rats fed natural ingredient NIH-31 diet, nucleotide-free purified AIN-76A diet or a basal diet similar to AIN-76A but deficient in the methyl donors folate, choline and methionine. Additional groups were fed AIN-76A or folate/methyl-deficient diets supplemented with 0.25% yeast RNA. Compared with NIH-31, AIN-76A increased dUMP/dTTP ratios, reduced the mitotic index (MI) and increased the ratio of proliferating cell index (PCI) to mitotic cells, an indication that hepatocytes were delayed in S-phase. Addition of yeast RNA to AIN-76A reversed (by approximately 50%) the effects of AIN-76A on dUMP/dTTP and cell proliferation. A folate/methyl-deficient diet also produced an increased dUMP/dTTP ratio and markedly reduced the MI, increasing the PCI/MI, which suggested even further delay of cells in S-phase. Addition of yeast RNA to the folate/methyl-deficient diet was effective in significantly reversing the effects of folate/methyl deficiency.


Mono- and bis(aminomethyl)phenylacetic acid esters as short-acting antiarrhythmic agents. 2.
The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrrolidinomethyl)-4-hydroxyphenylacetic acid series, the 1,4-benzodioxanyl-2-methyl(3q) and the thienyl-2-methyl(31) esters were evaluated in vivo for antiarrhythmic efficacy. In addition, a number of monoappended phenylacetic esters of 3q with or without the 4-hydroxy group were also prepared for evaluation of antiarrhythmic, lipophilic, and metabolic properties. Of these compounds, 3q possessed the most desirable pharmacological and pharmacokinetic profile.


High-performance genotypes in an introduced plant: insights to future invasiveness.
Maintaining high reproductive output in diverse conditions has consistently been found to promote invasiveness in introduced taxa. Following on this key observation, studies have compared the performance across environments of invasive vs. native congeners, and of introduced vs. native populations within invasive species. Performance differences among genotypes within introduced species have received far less attention, although such genetic variation could be critical to invasive potential. If an introduced species contains genotypes that can maintain high fitness across contrasting environments, such broadly adaptive, high-performance genotypes could promote and shape the species' immediate spread across multiple habitats. Furthermore, their presence could lead to the evolution of greater aggressiveness in the species, as these high performers increase in frequency. We investigated the existence and distribution of high-performance genotypes in Polygonum cespitosum, a newly invasive Asian annual. We raised 416 genotypes, collected from 14 North American populations, under resource-rich conditions to identify potential high-performance genotypes (the top 5% in total reproductive output). We then compared their fitness, life history, and functional traits to a random group of the remaining genotypes in three contrasting environments to ask the following: (1) Do consistently high-performance genotypes (i.e., genotypes with high relative fitness in diverse conditions) exist within introduced-range populations? (2) If so, do these high-performance genotypes possess distinctive life history and/or functional traits? (3) Do these genotypes occur in all populations or in only a subset of populations? Genotypes initially identified as high-performance in favorable conditions also had higher reproductive output in resource-limited environments. Their fitness advantage compared with control genotypes varied in magnitude from one environment to another but was significant within all three test environments. High-performance genotypes shared a developmental syndrome characterized by rapid and high germination, fast seedling growth, early reproductive onset, and high reproductive allocation, but they did not differ in other functional traits. P. cespitosum includes a subset of genotypes with accelerated development and significantly greater fitness in both favorable and stressful conditions. The nonrandom distribution of these high-performance genotypes among populations in the species' introduced range highlights the importance of genotypic and population-level variation for invasion dynamics.


Reversing effect of exogenous WWOX gene expression on malignant phenotype of primary cultured lung carcinoma cells.
Whether WW domain containing oxidoreductase (WWOX) gene is a tumor-suppressor is still controversial. Some researchers found that the transcription of the WWOX gene was lacking not only in tumor tissues but also in non-tumorous tissues and sometimes in normal tissues. Hence it is important to explore the role of the expression of the exogenous WWOX gene in the proliferation and apoptosis of primary cultured lung carcinoma cells. Lipofection technique was used to determine primary cultured lung carcinoma cells containing the highly expressed exogenous WWOX gene and primary cultured cells with vectors as controls. An animal model of lung cancer was made by subcutaneous implantation of tumor cells into nude mice. RT-PCR, Western blotting, flow cytometry, and TUNEL were used to detect the transcription, expression of the exogenous gene and the effect of the expression of targeted genes on the proliferation and apoptosis of the primary cultured lung carcinoma cells. The growth, clone formation rate (CFR) ((5.33 +/- 1.53)%) of the primary lung cancer cells transfected with the WWOX gene, tumor size and weight were significantly lower than those of the non-transfected lung cancer cells (CFR: (14.33 +/- 1.53)%) and the primary lung cancer cells transfected with blank plasmids (CFR: (11.00 +/- 1.73)%, P < 0.05). The apoptosis level of primary lung cancer cells transfected with the WWOX gene ((40.72 +/- 5.20)%) was significantly higher than that of the non-transfected lung cancer cells ((2.76 +/- 0.02)%) and the primary lung cancer cells transfected with blank plasmids ((2.72 +/- 0.15)%, P < 0.05). The expression of the exogenous WWOX gene can significantly inhibit the proliferation of lung cancer cells and induce their apoptosis, suggesting that the WWOX gene possesses tumor-suppressing effect.


Anti-Phospholipid Antibodies in Women with Placenta-Mediated Complications Delivered at >34 Weeks of Gestation.
To determine the prevalence of positive antiphospholipid (aPL) antibodies among pregnant women with placenta-mediated complications delivered at >340/7 weeks of gestation. This was a single-center retrospective observational study conducted between 2017 and 2022. Inclusion criteria included pregnant or post-partum women, >18 years, diagnosed with any of the following placenta-mediated complications and delivered at >340/7 weeks of gestation: small-for-gestational-age neonate (SGA ≤ 5th percentile according to local birthweight charts), preeclampsia with severe features, and placental abruption. The primary outcome was the prevalence of positive aPL antibodies: Lupus anticoagulant, Anticardiolipin, or Anti-ß2glycoprotein1. Overall, 431 women met the inclusion criteria. Of them, 378(87.7%) had an SGA neonate, 30 had preeclampsia with severe features (7%), 23 had placental abruption (5.3%), and 21 patients had multiple diagnoses(4.9%). The prevalence of aPL antibodies in the cohort was 4.9% and was comparable between the three subgroups (SGA-3.9%; PET with severe features-3.3%; and placental abruption-13% (p = 0.17)). aPL antibodies prevalence in women with placenta-mediated complications > 34 weeks of gestation was 4.9%, with comparable prevalence rates among the three subgroups. Future prospective studies are needed to delineate the need for treatment in those who tested positive for aPL antibodies and do not meet Anti-Phospholipid Antibody Syndrome clinical criteria.


Xylosylated Detoxification of the Rice Flavonoid Phytoalexin Sakuranetin by the Rice Sheath Blight Fungus Rhizoctonia solani.
Sakuranetin (1) is a rice flavanone-type phytoalexin. We have already reported that the metabolites from the detoxification of 1 by Pyriculariaoryzae are naringenin (2) and sternbin. In this study, we investigated whether the rice sheath blight fungus Rhizoctoniasolani, another major rice pathogen, can detoxify 1. The extract of R. solani suspension culture containing 1 was analyzed by LC-MS to identify the metabolites of 1. Three putative metabolites of 1 were detected in the extract from the R. solani suspension culture 12 h after the addition of 1, and they were identified as 2, sakuranetin-4'-O-β-d-xylopyranoside (3), and naringenin-7-O-β-d-xylopyranoside (4) by NMR, LC-MS/MS, and GC-MS analyses. The accumulation of 2, 3, and 4 reached their maximum levels 9-12 h after the addition of 1, whereas the content of 1 decreased to almost zero within 9 h. The antifungal activities of 3 and 4 against R. solani were negligible, and 2 showed weaker antifungal activity than 1. We concluded that 2, 3, and 4 are metabolites from the detoxification of 1 by R. solani. Xylosylation is a rare and efficient detoxification method for phytoalexins.


Sweat gland density and response during high-intensity exercise in athletes with spinal cord injuries.
Sweat production is crucial for thermoregulation. However, sweating can be problematic for individuals with spinal cord injuries (SCI), as they display a blunting of sudomotor and vasomotor responses below the level of the injury. Sweat gland density and eccrine gland metabolism in SCI are not well understood. Consequently, this study examined sweat lactate (S-LA) (reflective of sweat gland metabolism), active sweat gland density (SGD), and sweat output per gland (S/G) in 7 SCI athletes and 8 able-bodied (AB) controls matched for arm ergometry VO2peak. A sweat collection device was positioned on the upper scapular and medial calf of each subject just prior to the beginning of the trial, with iodine sweat gland density patches positioned on the upper scapular and medial calf. Participants were tested on a ramp protocol (7 min per stage, 20 W increase per stage) in a common exercise environment (21±1°C, 45-65% relative humidity). An independent t-test revealed lower (p<0.05) SGD (upper scapular) for SCI (22.3 ±14.8 glands · cm(-2)) vs. AB. (41.0 ± 8.1 glands · cm(-2)). However, there was no significant difference for S/G between groups. S-LA was significantly greater (p<0.05) during the second exercise stage for SCI (11.5±10.9 mmol · l(-1)) vs. AB (26.8±11.07 mmol · l(-1)). These findings suggest that SCI athletes had less active sweat glands compared to the AB group, but the sweat response was similar (SLA, S/G) between AB and SCI athletes. The results suggest similar interglandular metabolic activity irrespective of overall sweat rate.


Introital bacterial flora - effect of increased frequency of micturition.
Introital swabbing was performed on each of 20 premenopausal female volunteers over a 5-day period, 2 swabs being collected each day. During the last 3 days of the 5-day period the volunteers were requested to void every 2 hours. Analysis of our data shows: 1. Perineal bacterial flora varies in number and type of organisms from hour to hour and day to day. 2. Quantitative culturing is of little help in distinguishing colonisation of the introitus with urinary pathogens from mere intermittent contamination of the introitus with the same pathogens. 3. Our results suggest that 4 or more consecutive isolates of the potential urinary pathogens from the introitus over a 48-hour period signify colonisation. 4. Frequency of micturition increases the risk of colonisation of the introitus with potential urinary pathogens. The significance of these findings is discussed, in relation to the previous work of other investigators.


Impact of ageing on problem size and proactive interference in arithmetic facts solving.
Arithmetic facts (AFs) are required when solving problems such as "3 × 4" and refer to calculations for which the correct answer is retrieved from memory. Currently, two important effects that modulate the performance in AFs have been highlighted: the problem size effect and the proactive interference effect. The aim of this study is to investigate possible age-related changes of the problem size effect and the proactive interference effect in AF solving. To this end, the performance of young and older adults was compared in a multiplication production task. Furthermore, an independent measure of proactive interference was assessed to further define the architecture underlying this effect in multiplication solving. The results indicate that both young and older adults were sensitive to the effects of interference and of the problem size. That is, both interference and problem size affected performance negatively: the time needed to solve a multiplication problem increases as the level of interference and the size of the problem increase. Regarding the effect of ageing, the problem size effect remains constant with age, indicating a preserved AF network in older adults. Interestingly, sensitivity to proactive interference in multiplication solving was less pronounced in older than in younger adults suggesting that part of the proactive interference has been overcome with age.


[The use of rapid tests for individual diagnosis of influenza].
Antiviral therapy against influenza requires the beginning of treatment within 36 to 48 h after the onset of symptoms. With the availability of the neuraminidase inhibitors which are effective against influenza A and B a rapid diagnosis of influenza is of increasing interest. A diagnosis during the first consultation would be ideal for treatment. This can be achieved with clinical diagnosis and with quick tests that can be conducted in the practice (point of care test). The costs of such virological examinations have to be considered in relation to the use of information they create. The cost benefit relation is discussed in relation with different epidemic situations. The benefit and additional information of tests for individual diagnosis is high when the incidence of influenza is low, while in periods with high incidences the clinical diagnosis alone appears sufficient.


Correction of the transposition of the great arteries.
Inversion of the atrial flow in transposition of the great arteries is achieved in the following way: the remaining atrial septum is detached from behind, leaving it as a flap between both AV-valves. The incision is continued into the coronary sinus and the Vena magna cordis to the base of the left atrial appendage along the mitral ring. The resulting flap from the split coronary sinus is sutured to the left atrial wall in front of the left side pulmonary veins, thus forming a septum dorsal to the caval veins, diverting the left pulmonary venous blood to the right side. The atrial septal flap is reattached in front of the caval vein orifices. In 50 cases a small Dacron patch was used to complete the midportion of the new septum. Six patients died and so far we have encountered one superior Vena cava stenosis and one pulmonary vein stenosis. In 16 patients completion of the midportion of the new atrial septum was done with a partially excised flap from the right atrial wall still attached to the Vena cava inferior. This method resulted in 3 operative deaths. In 42 of 58 survivors the ECG has been repeatedly controlled 3 months to 6 years postoperatively. Thirty-six of the 42 patients have sinus rhythm, 4 vary between nodal and sinus-rhythm and 2 have a total AV-dissociation.


Screening of quorum sensing peptides for biological effects in neuronal cells.
Quorum sensing peptides (QSP) are an important class of bacterial peptides which can have an effect on human host cells. These peptides are used by bacteria to communicate with each other. Some QSP are able to cross the blood-brain barrier and reach the brain parenchyma. However, nothing is known about the effects of these peptides in the brain. Therefore, 85 quorum sensing peptides were screened on six different neuronal cell lines using MTT toxicity, neurite differentiation, cytokine production and morphology as biological outcomes. This primary screening resulted in 22 peptides with effects observed on neuronal cell lines, indicating a possible role in the gut-brain axis. Four peptides (Q138, Q143, Q180 and Q212) showed induction of neurite outgrowth while two peptides (Q162 and Q208) inhibited NGF-induced neurite outgrowth in PC12 cells. Eight peptides (Q25, Q135, Q137, Q146, Q151, Q165, Q208 and Q298) induced neurite outgrowth in human SH-SY5Y neuroblastoma cells. Two peptides (Q13 and Q52) were toxic for SH-SY5Y cells and one (Q123) for BV-2 microglia cells based on the MTT assay. Six peptides had an effect on BV-2 microglia, Q180, Q184 and Q191 were able to induce IL-6 expression and Q164, Q192 and Q208 induced NO production. Finally, Q75 and Q147 treated C8D1A astrocytes demonstrated a higher fraction of round cells. Overall, these in vitro screening study results indicate for the first time possible effects of QSP on neuronal cells.


Association of Cytokines With Exosomes in the Plasma of HIV-1-Seropositive Individuals.
Human immunodeficiency virus (HIV)-infected and viremic individuals exhibit elevated levels of plasma cytokines. Here we show that most cytokines are not in free form but appear associated with exosomes that are distinct from virions. Purified exosomes were analyzed to determine the levels of 21 cytokines and chemokines and compared with exosome-depleted plasma. Most cytokines were markedly enriched in exosomes from HIV-positive individuals relative to negative controls and to plasma. Moreover, exposure of naive peripheral blood mononuclear cells to exosomes purified from HIV-positive patients induced CD38 expression on naive and central memory CD4(+) and CD8(+) T cells, probably contributing to inflammation and viral propagation via bystander cell activation.


Relationship between Appetite, Food Intake and Body Composition among Elderly Malays from an Urban Residential Area in Kuala Lumpur, Malaysia.
Loss of appetite, decrease in food intake and changes in body composition appear to be inter-related factors that can influence the well-being of older individuals. Therefore, a study was conducted to determine the level of appetite, food intake and its relation to body composition and functional status among noninstitutionalised elderly Malays in Cheras, Kuala Lumpur. The Council on Nutrition Appetite Questionnaire (CNAQ), Diet History Questionnaire (DHQ), Bio-impedance Analysis (BIA) and Instrumental Activity of Daily Living (IADL) questionnaire and handgrip dynamometer were used to measure appetite, food intake, body composition and functional status respectively. A total of 112 subjects (41.1% men and 58.9% women) participated with mean age being 66.0 ± 5.0 years for men and 66.3 ± 6.2 years for women. Prevalence of poor appetite was higher in elderly women (72.3%) than in men (52.3%) (p<0.05). Pearson's correlation test showed that CNAQ score correlated significantly with age (r=-0.255, p<0.01), energy intake (r=0.272, p<0.01), IADL score (r=0.408, p<0.01) and handgrip strength (r=0.263, p<0.05). Energy intake correlated significantly with fat free mass (r=0.424, p<0.05), muscle mass (r=0.456, p<0.05) and total body water (r=0.403, p<0.05). Multiple regression analysis showed that 27.0% of poor appetite could be explained by advanced age, low energy intake and decreased functional status. In conclusion, the study showed that poor appetite was prevalent among the subjects, especially women and this was influenced by aging, inadequate energy intake and decreased functional status.


[Optimization of the therapy of atopic dermatitis by means of immunotherapy].
Taking into account disturbances in the functioning of the immune system in atopic dermatitis (AD) and the potentiating role of staphylococcal and other infections, the possibility of the optimization of the therapy of AD with the use of preparations having immunomodulating action and immunogenic activity is proposed. In the complex therapy of AD in children we used polycomponent vaccine Immunovac B-4, introduced intranasally and orally. Under the influence of immunotherapy the clinical characteristics of the patients had pronounced positive dynamics. A considerable decrease in the spread of the process, the degree of its severity and subjective symptoms was noted shortly after the course of vaccine treatment. Simultaneously the SCORAD index dropped from 64.5 to 39.4. During the later period of observation further decrease in the severity of the course of AD in children occurred, and the minimal characteristics were observed in 6 months of observation. At that time the SCORAD index fell to 19.9 +/- 1.34. The volume of pharmacotherapy and the number of acute respiratory infections considerably decreased, the positive dynamics of the quantitative and qualitative composition of the intestinal microflora was noted. The prolonged immunotherapeutic effect of the polycomponent vaccine made it possible to recommend the vaccine for the optimization of the therapy of AD.


An envisioned bridge: schooling as a neurocognitive developmental institution.
The potential contribution of social science research to close the gap of knowledge between cognitive neuroscience and educational research has been underappreciated. Despite their virtual absence in the interdisciplinary dialog of neuroscience, sociology of education and related study of the cultural impact of formal education have generated research relevant to an understanding of how the social environment, such as widespread schooling, co-evolves with, and enhances neurocognitive development. Two clusters of isolated research literatures are synthesized that taken together anticipates a dynamic integration of neuroscience and education. The first cluster is on the social construction of cognition through formal education in contemporary society, including the effects of schooling on neurological and cognitive development; the demographic expansion of exposure to the developmental influence of schooling; and education's cultural impact on the meaning of the learning experience and reinforcement of cognition as the key human capability across ever more key institutions in postindustrial society. The second cluster turns the issue around by examining current investigations from neuroscience that support neurological hypotheses about the causes behind the schooling effect on neurocognitive development. We propose that further integration of these literatures will provide a more ecologically valid context in which to investigate the evolving functional architecture of the contemporary brain.


Gene expression analyses implicate an alternative splicing program in regulating contractile gene expression and serum response factor activity in mice.
Members of the CUG-BP, Elav-like family (CELF) regulate alternative splicing in the heart. In MHC-CELFΔ transgenic mice, CELF splicing activity is inhibited postnatally in heart muscle via expression of a nuclear dominant negative CELF protein under an α-myosin heavy chain promoter. MHC-CELFΔ mice develop dilated cardiomyopathy characterized by alternative splicing defects, enlarged hearts, and severe contractile dysfunction. In this study, gene expression profiles in the hearts of wild type, high- and low-expressing lines of MHC-CELFΔ mice were compared using microarrays. Gene ontology and pathway analyses identified contraction and calcium signaling as the most affected processes. Network analysis revealed that the serum response factor (SRF) network is highly affected. Downstream targets of SRF were up-regulated in MHC-CELFΔ mice compared to the wild type, suggesting an increase in SRF activity. Although SRF levels remained unchanged, known inhibitors of SRF activity were down-regulated. Conversely, we found that these inhibitors are up-regulated and downstream SRF targets are down-regulated in the hearts of MCKCUG-BP1 mice, which mildly over-express CELF1 in heart and skeletal muscle. This suggests that changes in SRF activity are a consequence of changes in CELF-mediated regulation rather than a secondary result of compensatory pathways in heart failure. In MHC-CELFΔ males, where the phenotype is only partially penetrant, both alternative splicing changes and down-regulation of inhibitors of SRF correlate with the development of cardiomyopathy. Together, these results strongly support a role for CELF-mediated alternative splicing in the regulation of contractile gene expression, achieved in part through modulating the activity of SRF, a key cardiac transcription factor.


Compact sample environment for in situ X-ray scattering during spin-coating.
We demonstrate a compact sample environment for the in situ study of crystallization kinetics of thin films on synchrotron beamlines, featuring atmospheric control, automated deposition, spin-coating, and annealing stages. The setup is suitable for studying thin film growth in real time using grazing-incidence X-ray diffraction techniques. Humidity and oxygen levels are being detected by sensors. The spinning stage exhibits low vertical oscillation amplitude (∼3μm at speeds up to 10 000 rpm) and can optionally be employed for antisolvent application or gas quenching to investigate the impact of these techniques, which are often used to assist thin film growth. Differential reflectance spectroscopy is implemented in the spin-coater environment for inspecting thin film thickness and optical properties. The infrared radiation-based annealing system consists of a halogen lamp and a holder with an adjustable lamp-to-sample distance, while the sample surface temperature is monitored by a pyrometer. All features of the sample environment can be controlled remotely by the control software at synchrotron beamlines. In order to test and demonstrate the performance, the crystallization pathway of the antisolvent-assisted MAPbI3 (MA = methylammonium) perovskite thin film during the spinning and annealing stages is monitored and discussed.


Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol.
Triple negative breast cancer (TNBC) is difficult to treat since it lacks all the three most commonly targeted hormone receptors. Patients afflicted with TNBC are treated with platinum core chemotherapeutics, such as cisplatin. Despite the initial effective anticancer effects of cisplatin, TNBC attenuates its effect and develops resistance eventually, which results in tumor reoccurrence. Hence, there is a critical demand for effective, alternative, and natural ways to treat TNBC. Towards this, a promising technique for inhibiting TNBC cell proliferation involves promoting the production of reactive oxygen species (ROS), which triggers pro-apoptotic caspases 9 and 3. Resveratrol (RESV), an active bio compound found in naturally available fruits, such as grapes, is utilized in this research for that. In addition, electrochemotherapy (ECT), which involves the application of electrical pulses (EP), was utilized to enhance the uptake of RESV. MDA-MB-231, human TNBC cells were treated with/out RESV, and eight 600-1,000 V/cm, 100 μs pulses at 1 Hz. The cells were characterized by using various assays, including viability assay, and ROS assay. A TNBC cell viability of as low as 20% was obtained at 24 h (it was 13% at 60 h), demonstrating the potential of this novel treatment. ROS production was the highest in the combination of EP at 1,000 V/cm along with RESV at 100 μmol/L. Results indicate that RESV has the potential as an anti-TNBC agent and that EP + RESV can significantly enhance the cell death to reduce MDA-MB-231 cell viability by increasing ROS production and triggering apoptosis.


Multiple Sclerosis Pathology.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain. In this review, the spectrum of MS lesions and their relation to the inflammatory process is described. Pathology suggests that inflammation drives tissue injury at all stages of the disease. Focal inflammatory infiltrates in the meninges and the perivascular spaces appear to produce soluble factors, which induce demyelination or neurodegeneration either directly or indirectly through microglia activation. The nature of these soluble factors, which are responsible for demyelinating activity in sera and cerebrospinal fluid of the patients, is currently undefined. Demyelination and neurodegeneration is finally accomplished by oxidative injury and mitochondrial damage leading to a state of "virtual hypoxia."


Black licorice ingestion: Yet another confounding agent in patients with melena.
We describe an 80-year-old woman with atrial fibrillation, anti-coagulated with warfarin, who on two separate occasions developed black tarry stools and an elevated international normalized ratio (INR) after eating a pound of Black Licorice. During her most recent episode, her hematocrit was 14 (baseline 34) and her INR was 5.5 (baseline 2.1). She was advised to restrict licorice consumption, and a follow-up INR two weeks later was 1.2. Black Licorice is derived from the root of the plant, Glycyrrhiza glabra. The components of its extract inhibit the P450 system enzymes that metabolize Warfarin, inhibit thrombin, and prolong fibrinogen clotting times. Hence, the anti-thrombotic activity and inhibition of warfarin metabolism might synergistically amplify anti-coagulation. The presence of Black Licorice in the stool can also mimic melena and confound its clinical presentation. Health care providers should caution patients who are at risk for bleeding or on warfarin to avoid black licorice due to an elevated risk of gastrointestinal bleeding.


Asn- and Asp-mediated interactions between transmembrane helices during translocon-mediated membrane protein assembly.
Inter-helix hydrogen bonding involving asparagine (Asn, N), glutamine (Gln, Q), aspartic acid (Asp, D) or glutamic acid (Glu, E) can drive efficient di- or trimerization of transmembrane helices in detergent micelles and lipid bilayers. Likewise, Asn-Asn and Asp-Asp pairs can promote the formation of helical hairpins during translocon-mediated membrane protein assembly in the endoplasmic reticulum. By in vitro translation of model integral membrane protein constructs in the presence of rough microsomes, we show that Asn- or Asp-mediated interactions with a neighbouring transmembrane helix can enhance the membrane insertion efficiency of a marginally hydrophobic transmembrane segment. Our observations suggest that inter-helix hydrogen bonds can form during Sec61 translocon-assisted insertion and thus could be important for membrane protein assembly.


Screening of predicted synergistic multi-target therapies in glioblastoma identifies new treatment strategies.
IDH-wildtype glioblastoma (GBM) is a highly malignant primary brain tumor with a median survival of 15 months after standard of care, which highlights the need for improved therapy. Personalized combination therapy has shown to be successful in many other tumor types and could be beneficial for GBM patients. We performed the largest drug combination screen to date in GBM, using a high-throughput effort where we selected 90 drug combinations for their activity onto 25 patient-derived GBM cultures. 43 drug combinations were selected for interaction analysis based on their monotherapy efficacy and were tested in a short-term (3 days) as well as long-term (18 days) assay. Synergy was assessed using dose-equivalence and multiplicative survival metrics. We observed a consistent synergistic interaction for 15 out of 43 drug combinations on patient-derived GBM cultures. From these combinations, 11 out of 15 drug combinations showed a longitudinal synergistic effect on GBM cultures. The highest synergies were observed in the drug combinations Lapatinib with Thapsigargin and Lapatinib with Obatoclax Mesylate, both targeting epidermal growth factor receptor and affecting the apoptosis pathway. To further elaborate on the apoptosis cascade, we investigated other, more clinically relevant, apoptosis inducers and observed a strong synergistic effect while combining Venetoclax (BCL targeting) and AZD5991 (MCL1 targeting). Overall, we have identified via a high-throughput drug screening several new treatment strategies for GBM. Moreover, an exceptionally strong synergistic interaction was discovered between kinase targeting and apoptosis induction which is suitable for further clinical evaluation as multi-targeted combination therapy.


Spontaneous internal carotid artery occlusion and rapid cerebral aneurysm progression: case series and literature review.
An accurate determination of the natural history of a cerebral aneurysm has implications on management. Few risk factors other than female gender and cigarette smoking have been identified to be associated with cerebral aneurysm progression, particularly rapid progression. This case series and literature review serves to illustrate a relationship between spontaneous carotid occlusion and rapid enlargement of cerebral aneurysms. In our case series, we demonstrated that increased hemodynamic stress on collateral vessels caused by a spontaneous carotid occlusion may contribute to unusually rapid aneurysm growth and/or rupture. Spontaneous carotid occlusive disease may be considered a risk factor for rapid cerebral aneurysm progression and/or rupture that may warrant more aggressive management options, including more frequent surveillance imaging in previously treated aneurysms.


Quantifying glenoid bone loss arthroscopically in shoulder instability.
Our goal was to establish a consistent methodology for quantifying glenoid bone loss by arthroscopic means. This study was an anatomic investigation of glenoid structure and its consistent anatomic landmarks as determined by arthroscopic means in live subjects and by direct measurement in fresh-frozen cadaver specimens. We arthroscopically evaluated and measured the location of the bare spot of the glenoid in 56 subjects that had no evidence of instability (average age, 40 years). We also measured the exact location of the glenoid bare spot in 10 cadaver shoulders (average age, 76 years). The bare spot of the glenoid was a consistent reference point from which to determine glenoid bone loss because it was located almost exactly at the center of the circle that was defined by the articular margin of the inferior glenoid below the level of the midglenoid notch. The tightly clustered standard deviations of the bare spot measurements in both the live subjects and the cadaver specimens confirmed its consistent location. The glenoid bare spot can be used as a central reference point to quantify the percentage bone loss of the inferior glenoid. Such objective measurement of glenoid bone loss can be clinically useful to the surgeon in deciding whether bone grafting is necessary to restore stability to the shoulder with a bone-deficient glenoid.