[The EMG findings of spasmodic torticollis--the character of the EMG findings of neurogenic torticollis].
Spasmodic torticollis is a clinical entity that is hard to treat though various symptomatic therapy have been tried. On the other hand, microvascular decompression operation have been established for cranial nerve vascular compression syndrome such as hemifacial spasm. Case reports on the decompression of the spinal accessory nerve for the treatment of spasmodic torticollis have been published on the basis of the concept of cranial nerve vascular compression syndrome. Thus, spasmodic torticollis related to unilateral accessory nerve has attracted much attention for selecting an optimal treatment, although there have not been any diagnostic criteria with electromyographic study. From the viewpoint of the clinical electrophysiological findings on hemifacial spasm those we have acquired by EMG study, we have examined the EMG findings of various types of spasmodic torticollis and here report the classification of spasmodic torticollis based on the EMG study. Thirty-five patients with spasmodic torticollis were analyzed. The symptoms were classified to the horizontal rotation type, the lateral bending type and the mixed type with the number of each group of 23, 2 and 10, respectively. As we have shown the criteria of the EMG findings on hemifacial spasm, the EMG of the patients with spasmodic torticollis were analyzed on four conditions as follows; (1) distribution of the involved muscles, (2) maximum firing rate of the abnormal spontaneous activity of the sternocleidomastoid muscle, (3) synkinetic discharge between the muscles innervated by unilateral accessory nerve and (4) alteration of the spontaneous muscle discharge by posture change. Abnormal spontaneous muscle discharges were recorded only from the sternocleidomastoid muscle and the trapezius muscle on the same side in twelve patients. Maximum firing rate of spontaneous muscle discharge was higher than that of maximum voluntary contraction in twenty-two patients. Abnormal synkinetic discharge was recorded between the sternocleidomastoid muscle and the trapezius muscle on the same side in twenty-one patients. Spontaneous EMG activities of the muscles innervated by the accessory nerve increased when the patients stood up from the resting supine position in thirty-one patients. Thus, ten patients out of thirty-five subjects had all four conditions mentioned above as typical patients with hemifacial spasm usually had. These ten patients with spasmodic torticollis were thought to have strong similarity to the EMG characteristics of hemifacial spasm that suggested hyperexcitability of unilateral accessory nervous system. This classification with EMG is considered to be useful in diagnosing the spasmodic torticollis related to unilateral accessory nerve and can be applied for selecting an optimal treatment.


Extracellular ATP is an autocrine/paracrine regulator of hypoxia-induced adventitial fibroblast growth. Signaling through extracellular signal-regulated kinase-1/2 and the Egr-1 transcription factor.
Important autocrine/paracrine functions for the adenine nucleotides have been proposed in several tissues. We addressed the possibility that extracellular ATP would modulate/mediate hypoxia-induced adventitial fibroblast growth. Acute hypoxia (3% O(2), 10-60 min) increased extracellular ATP concentrations in adventitial fibroblasts and in lung microvascular endothelial cells, and chronic hypoxia (3% O(2), 14-30 days) markedly attenuated the rate of extracellular ATP hydrolysis by ecto-nucleotidase(s). Exogenous ATP stimulated [(3)H]thymidine incorporation in fibroblasts as did UTP, ADPbeta, 2-methylthioadenosine triphosphate, adenosine 5'-(alpha,beta-methylene)triphosphate, and benzoylbenzoyl-ATP (2'-3'-O-(4-benzoylbenzoyl)-ATP), indicating that both P2Y and P2X purinoceptors can mediate mitogenic responses. Suramin (100 microm), Cibacron blue 3GA (100 microm), and pyridoxalphosphate-6-azophenyl-2',-4'-disulfonic acid (100 microm) as well as apyrase (5 units/ml) attenuated hypoxia- and ATP-induced and DNA synthesis, indicating activation and a functional role of purinoceptors under hypoxic conditions. ATP-induced DNA synthesis was augmented by hypoxia in an additive fashion, whereas ATP and hypoxia synergistically increased growth factor-induced DNA synthesis, again suggesting that ATP and hypoxia utilize similar signaling pathways to induce proliferation. Indeed, we found that ATP (100 microm) and hypoxia (3% O(2)) induced expression and activation of Egr-1 transcription factor, and both stimuli acted, in part, through a G(alpha)(i)/ERK1/2-dependent signaling pathway. Suramin, Cibacron blue 3GA, and apyrase attenuated hypoxia-induced ERK1/2 activation and Egr-1 expression. We conclude that hypoxia induces ATP release from endothelial cells and fibroblasts and that the activation of P2 purinoceptors is involved in the regulation of DNA synthesis by fibroblasts under hypoxic conditions.


The gorgonian coral Eunicella labiata hosts a distinct prokaryotic consortium amenable to cultivation.
Microbial communities inhabiting gorgonian corals are believed to benefit their hosts through nutrient provision and chemical defence; yet much remains to be learned about their phylogenetic uniqueness and cultivability. Here, we determined the prokaryotic community structure and distinctiveness in the gorgonian Eunicella labiata by Illumina sequencing of 16S rRNA genes from gorgonian and seawater metagenomic DNA. Furthermore, we used a 'plate-wash' methodology to compare the phylogenetic diversity of the 'total' gorgonian bacteriome and its 'cultivatable' fraction. With 1016 operational taxonomic units (OTUs), prokaryotic richness was higher in seawater than in E. labiata where 603 OTUs were detected, 68 of which were host-specific. Oceanospirillales and Rhodobacterales predominated in the E. labiata communities. One Oceanospirillales OTU, classified as Endozoicomonas, was particularly dominant, and closest relatives comprised exclusively uncultured clones from other gorgonians. We cultivated a remarkable 62% of the bacterial symbionts inhabiting E. labiata: Ruegeria, Sphingorhabdus, Labrenzia, other unclassified Rhodobacteraceae, Vibrio and Shewanella ranked among the 10 most abundant genera in both the cultivation-independent and dependent samples. In conclusion, the E. labiata microbiome is diverse, distinct from seawater and enriched in (gorgonian)-specific bacterial phylotypes. In contrast to current understanding, many dominant E. labiata symbionts can, indeed, be cultivated.


Response to ban on smoking in public places--a cross-sectional study.
Smoking has become an important global problem that poses serious health hazards. Today even teenagers have got trapped by this addictive habit. To curb this menace, the Government of Tamilnadu has proposed a ban on smoking in public places by introducing the Bill "Tamilnadu Prohibition of Smoking and Spitting 2002". A study was conducted in the month of February, 2003 to find out the response to this proposed ban among health providers. One hundred and twenty-seven hospital employees were studied using a one page questionnaire. The prevalence of smoking was found to be 12.6% (95% CI 6.9 to 18.3). The response of the study group to the proposed ban was recorded by asking them about their awareness, acceptability and their personal opinion about the ban. It was found that 94% of the smokers and 83% of the non-smokers were aware of the proposed ban and 50% of the smokers and 69% of non-smokers wanted the ban to be implemented. It was also found that 43.8% of the smokers and 52.3% of the non-smokers were confident that the ban on smoking in public places will be effective. They were also of the opinion that awareness had to be increased and the penalties had to be implemented strictly. Further studies on other population groups may have to be taken upto know about the impact of this important Act after it comes into effect.


[Disordered permeability of the gastrointestinal tract barrier for macromolecules and the possibilities for its experimental dietetic correction].
Macromolecular absorption of food and microbial antigens being enhanced in the intestine under pathological conditions may well be the cause of such diseases as food allergy, coeliac disease, Crohn's disease, atopic eczema, etc. The polyethyleneglycol-4000 (PEG-4000) and food antigens absorption was found to be similar in the animal intestine. The PEG-4000 gastrointestinal permeability is considerably increased in the rats with anaphylaxis, experimental biliary malabsorption and experimental colitis. Fatty acids of the omega-3 and omega-6 series as well as histidine were found to change the permeability for the PEG-4000.


Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of rat hepatocarcinogenesis.
Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of hepatocarcinogenesis were examined by monitoring both hepatocyte injury and hepatocellular carcinoma development in F344 rats bearing preneoplastic liver nodules induced by the Cayama-Farber procedure. Redox-enzyme modulation, which included increased cytochrome P450 reductase activity induced by phenobarbital-Na (100 mg/kg, i.p. for 3 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.), depletion of glutathione by phorone (200 mg/kg, i.p.), supplementation with the Fe(III) sodium salt of EDTA (50 mg/kg, i.p.) and redox-cycling activation by menadione (50 mg/kg, i.g.), exerted no prominent hepatocyte injury within nodules but did cause slight injury in the surrounding hepatocytes in nodule-bearing rats. The same treatments induced severe hepatocyte injury in non-treated normal rats. Redox-enzyme modulation performed every other week for 33 weeks significantly reduced the number of hepatocellular carcinomas developing in nodule-bearing rats. These results indicate that preneoplastic nodules are resistant to the oxidative stress induction caused by redox-enzyme modulation treatment and that, despite toxic effects in surrounding hepatocytes, no progression pressure is exerted. Indeed, the treatment rather demonstrates an inhibitory effect of the evolution of the nodules into hepatocellular carcinomas.


[Evidence-based back pain care--a pilot study of continuous medical education].
Evidence-based practice guidelines on back pain give recommendations on appropriate care in order to improve patient outcomes. One strategy used to implement practice guidelines is continuous medical education (CME). Junior doctors working in a primary care emergency reception attended a CME programme with a lecture on back pain, a booklet on evidence-based back pain care and one day traineeship with a specialist working at a back pain clinic. Three to six months later the participants answered a questionnaire evaluating the programme. Ten out of the eleven participants answered the questionnaire. They felt that the CME programme had affected their professional practice; one in two thought that their practice still deviated from evidence-based recommendations, mostly because patients wanted faster interventions than the recommendations call for. Initiatives to implement evidence-based back pain care should focus on the important deviations from recommended care and specifically seek to affect barriers that maintain such practice.


Contrast enhancement in abdominal computed tomography: influence of photon energy of different scanners.
Different CT scanners have different X-ray spectra and photon energies indicating that contrast enhancement vary among scanners. However, this issue has not been fully validated; therefore, we performed phantom and clinical studies to assess this difference. Two scanners were used: scanner-A and scanner-B. In the phantom study, we compared the contrast enhancement between the scanners at tube voltage peaks of 80, 100 and 120 kVp. Then, we calculated the effective energies of the two CT scanners. In the clinical study, 40 patients underwent abdominal scanning with scanner-A and another 40 patients with scanner-B, with each group using the same scanning protocol. The contrast enhancement of abdominal organs was assessed quantitatively (based on the absolute difference between the attenuation of unenhanced scans and contrast-enhanced scans) and qualitatively. A two-tailed independent Student's t-test and or the Mann-Whitney U test were used to compare the discrepancies. In the phantom study, contrast enhancement for scanner-B was 36.9, 32.6 and 30.8% higher than that for scanner-A at 80, 100 and 120 kVp, respectively. The effective energies were higher for scanner-A than for scanner-B. In the quantitative analysis for the clinical study, scanner-B yielded significantly better contrast enhancement of the hepatic parenchyma, pancreas, kidney, portal vein and inferior vena cava compared with that of scanner-A. The mean visual scores for contrast enhancement were also significantly higher on images obtained by scanner-B than those by scanner-A. There were significant differences in contrast enhancement of the abdominal organs between the compared CT scanners from two different vendors even at the same scanning and contrast parameters. Advances in knowledge: Awareness of the impact of different X-ray energies on the resultant attenuation of contrast material is important when interpreting clinical CT images.


Selective degradation of maternal and embryonic transcripts in in vitro produced bovine oocytes and embryos using sequence specific double-stranded RNA.
RNA interference (RNAi) has been used for selective degradation of an mRNA transcript or inhibiting its translation to a functional protein in various species. Here, we applied the RNAi approach to suppress the expression of the maternal transcript C-mos and embryonic transcripts Oct-4 in bovine oocytes and embryos respectively, using microinjection of sequence-specific double-stranded RNA (dsRNA). For this, 435 bp C-mos and 341 bp Oct-4 dsRNA were synthesized and microinjected into the cytoplasm of immature oocytes and zygotes respectively. In experiment 1, immature oocytes were categorized into three groups: those injected with C-mos dsRNA, RNase-free water and uninjected controls. In experiment 2, in vitro produced zygotes were categorized into three groups: those injected with Oct-4 dsRNA, RNase-free water and uninjected controls. The developmental phenotypes, the level of mRNA and protein expression were investigated after treatment in both experiments. Microinjection of C-mos dsRNA has resulted in 70% reduction of C-mos transcript after maturation compared to the water-injected and uninjected controls (P<0.01). Microinjection of zygotes with Oct-4 dsRNA has resulted in 72% reduction in transcript abundance at the blastocyst stage compared to the uninjected control zygotes (P<0.01). Moreover, a significant reduction in the number of inner cell mass (ICM) cells was observed in Oct-4 dsRNA-injected embryos compared to the other groups. From oocytes injected with C-mos dsRNA, 60% showed the extrusion of the first polar body compared to 50% in water-injected and 44% in uninjected controls. Moreover, only oocytes injected with C-mos dsRNA showed spontaneous activation. In conclusion, our results demonstrated that sequence-specific dsRNA can be used to knockdown maternal or embryonic transcripts in bovine embryogenesis.


Synthesis and characterization of electrospun polyvinyl alcohol nanofibrous scaffolds modified by blending with chitosan for neural tissue engineering.
Among several attempts to integrate tissue engineering concepts into strategies to repair different parts of the human body, neuronal repair stands as a challenging area due to the complexity of the structure and function of the nervous system and the low efficiency of conventional repair approaches. Herein, electrospun polyvinyl alcohol (PVA)/chitosan nanofibrous scaffolds have been synthesized with large pore sizes as potential matrices for nervous tissue engineering and repair. PVA fibers were modified through blending with chitosan and porosity of scaffolds was measured at various levels of their depth through an image analysis method. In addition, the structural, physicochemical, biodegradability, and swelling of the chitosan nanofibrous scaffolds were evaluated. The chitosan-containing scaffolds were used for in vitro cell culture in contact with PC12 nerve cells, and they were found to exhibit the most balanced properties to meet the basic required specifications for nerve cells. It could be concluded that addition of chitosan to the PVA scaffolds enhances viability and proliferation of nerve cells, which increases the biocompatibility of the scaffolds. In fact, addition of a small percentage of chitosan to the PVA scaffolds proved to be a promising approach for synthesis of a neural-friendly polymeric blend.


The electromyographic silent period in Huntington's chorea--a comparison between childhood and adult values.
The electromyographic silent period produced by electrical stimulation of the median nerve was recorded in the abductor pollicis brevis muscle in a group of 7 patients with Huntington's chorea (5 adults and 2 children). The adults had short values of 60.0--75 ms, while the values in the children were within normal limits (90--140 ms). These results suggest: (i) that the short silent period in Huntington's chorea is due to reduced excitation (or increased inhibition) of spinal interneurons; and (ii) that Huntington's chorea in childhood differs from that in adults not only with regard to the clinical picture but with regard to silent period values elicited by stimulation of the median nerve.


Apparent Bicarbonate Uptake and Possible Plasmalemma Proton Efflux in Chara corallina.
It is shown that the apparent uptake of bicarbonate by cells of Chara corallina could be the result of a proton efflux coupled to extracellular production of CO(2) from bicarbonate, with CO(2) being taken up by the cell. The theoretical results presented here show that the influx of CO(2) across the plasmalemma can be much greater than previously thought, if there is a large efflux of protons across the plasmalemma, and that, if this occurs, there would be a much steeper gradient of pH near the cell surface than previously thought possible.


A case of dumbbell-shaped epidural cavernous angioma in the lumbar spine.
Most spinal cavernous haemangiomas occur in the vertebral body and purely extradural cavernous hemangiomas without any vertebral body involvement is rare and account for only 4% of all extradural spinal tumors. Dumbbell-shaped spinal cavernous angioma is extremely rare, only 10 cases have been reported in the literature. A 77-year-old female presented with a one-year history of lumbago and right-sided L3 dermatomal hypoesthesia. A dumbbell mass at the L2/3 vertebral level was identified on lumbar MRI. The lesion was irregularly shaped and isointense on T1W and hyperintense on T2W and DWI images with homogenous contrast enhancement. A presumptive diagnosis was schwannoma, but other malignant neoplasms were also considered because of its irregular shape, minimally dilated neural foramen and the involvement of the non-enhanced L3 nerve root. The patient underwent surgery with a lateral extracavitary approach. A histopathological examination revealed cavernous hemangioma. Cavernous hemangioma should be included in the differential diagnosis of dumbbell-shaped spinal tumors when the intervertebral foramina is not highly dilated and non-enhanced nerve root is identified in the tumor.


An In-Vitro Evaluation and Comparison of Apical Sealing Ability of Three Different Obturation Technique - Lateral Condensation, Obtura II, and Thermafil.
Success of non-surgical root canal treatment is predicted by meticulous cleaning and shaping of the root canal system, three-dimensional obturation and a well-fitting "leakage-free" coronal restoration. The techniques of obturation that are available have their own relative position in the historical development of filling techniques. Over the years, pitfalls with one technique have often led to the development of newer methods of obturation, along with the recognition that no one method of obturation may satisfy all clinical cases. A total of 120 extracted human permanent anterior maxillary and mandibular single rooted teeth were selected for the present study and divided into 3 groups based on the method of obturation technique. Following the preparation the patency at the apical foramen was confirmed by passing a file #15. After obturation of all three groups, teeth were immersed in 1% of aqueous methylene blue dye for a period of two weeks and then samples were subjected to spectrophotometric analysis. The present study was conducted to evaluate in vitro the spectrophotometric analysis to quantitatively analyze relative amount of dye penetration using lateral condensation (Group I), Obtura II (Group II ), Thermafil obturating technique (Group III) with ZOE sealer used in all groups. Teeth obturated with lateral condensation (Group I) shows mean value of 0.0243 and standard deviation of 0.0056. The Group II thermoplasticized injectable moulded Guttapercha (Obtura II) showed 0.0239 mean and standard deviation value of 0.0045 and Group III Thermafil obturation technique shows 0.0189 as mean value and 0.0035 standard deviation values. Following conclusion was drawn from the present study. Group III i.e., Thermafil obturating technique shows minimum mean apical dye penetration compared to Group II (ObturaII) and Group I (lateral condensation).Lateral condensation shows maximum mean apical dye penetration in all three groups.There is no significant difference between the apical dye penetration of lateral condensation and Obtura II. Obturation, lateral condensation, Obtura II, Thermafil, Spectrophotometer, dye penetration. How to cite this article: Samson E, Kulkarni S, Sushil K C, Likhitkar M. An In-Vitro Evaluation and Comparison of Apical Sealing Ability of Three Different Obturation Technique - Lateral Condensation, Obtura II, and Thermafil. J Int Oral Health 2013; 5(2):35-43.


Redox Sensor Array with 23.5-μm Resolution for Real-Time Imaging of Hydrogen Peroxide and Glutamate Based on Charge-Transfer-Type Potentiometric Sensor.
Towards clarifying the spatio-temporal neurotransmitter distribution, potentiometric redox sensor arrays with 23.5-µm resolution were fabricated. The sensor array based on a charge-transfer-type potentiometric sensor comprises 128×128 pixels with gold electrodes deposited on the surface of pixels. The sensor output corresponding to the interfacial potential of the electrode changed logarithmically with the mixture ratio of K3Fe(CN)6 and K4Fe(CN)6, where the redox sensitivity reached 49.9 mV/dec. By employing hydrogen peroxidase as an enzyme and ferrocene as an electron mediator, the sensing characteristics for hydrogen peroxide (H2O2) were investigated. The analyses of the sensing characteristics revealed that the sensitivity was about 44.7 mV/dec., comparable to the redox sensitivity, while the limit of detection (LOD) was achieved to be 1 µM. Furthermore, the oxidation state of the electron mediator can be the key to further lowering the LOD. Then, by immobilizing oxidizing enzyme for H2O2 and glutamate oxidase, glutamate (Glu) measurements were conducted. As a result, similar sensitivity and LOD to those of H2O2 were obtained. Finally, the real-time distribution of 1 µM Glu was visualized, demonstrating the feasibility of our device as a high-resolution bioimaging technique.


Seroprevalence of COVID-19 infection among vaccine naïve population after the second surge (June 2020) in a rural district of South India: A community-based cross-sectional study.
To determine the seroprevalence of the SARS Cov 2 infection among vaccine naive population in a rural district of South India post-second surge. We conducted a cross-sectional study in the five villages of a randomly chosen sub-district in the Bangalore rural district. We did house to house surveys and recruited 831 vaccine naive adults in July 2021. We tested samples for the presence of antibodies (including IgG & IgM) to SARS CoV-2 using the Roche Elecsys SARS-CoV-2 -S assay that quantifies antibodies against the receptor-binding domain (RBD) of the spike (S) protein. We estimated an overall prevalence of 62.7% (95% CI: 59.3-66.0) and an age-and gender-adjusted seroprevalence of 44.9% (95% CI: 42.5-47.4). When adjusted for test performance, the seroprevalence was 74.64% (95% CI: 70.66-78.47). The case-to-undetected-infected ratio (CIR) was 1: 8.65 (95% CI 1:8.1-1:9.1), and the Infection Fatality Rate (IFR) was 16.27 per 100,00 infections as of 13 July 2021. A history of at least one symptom suggestive of COVID-19 or a positive COVID-19 test of self or a family member in the past were significantly associated with seropositivity. We report a high seroprevalence of COVID-19 infection despite the advantages of low population density and well-ventilated landscapes in rural areas. CIR and IFR were higher than the previous serosurvey conducted in the same population during the first surge. The thought of achieving herd immunity comes with relief. However, it's vital to put efforts into building population health and rural health infrastructure to avert future health catastrophes.


Markedly decreased expression of TAP1 and LMP2 genes in HLA class I-deficient human tumor cell lines.
HLA class I antigens of the human major histocompatibility complex play an important role in immune response. These molecules present foreign antigenic peptides to cytotoxic T lymphocytes and thereby play a role in the immune surveillance of cells infected with virus or other intracellular pathogens or altered by malignant transformation. A marked deficiency or lack of expression of these antigens has been reported in a variety of human neoplasms. In the present study, we examined the expression of class I alpha chain, beta 2-microglobulin, TAP (TAP1 and TAP2) and LMP (LMP2 and LMP7) genes in a number of human tumor cell lines including small-cell lung carcinoma, hepatocellular carcinoma, colon adenocarcinoma and basophilic leukaemia. These cell lines were deficient in expression of both class I alpha chain and beta 2-microglobulin gene products. In addition, these cell lines lacked the products of MHC-encoded proteasome subunit LMP2 as well as the putative peptide transporter TAP1 genes. In contrast, TAP2 and LMP7 genes were expressed in these cell lines. Treatment of cells with gamma-IFN markedly enhanced the expression of class I alpha chain, beta 2-microglobulin, TAP1 and LMP2 genes with a concomitant increase in cell-surface expression of class I molecules. The upregulation of TAP1 and LMP2 expression is associated with increased class I expression, suggesting that endogenous antigens, e.g. tumor antigens, could be presented by class I molecules following treatment of tumor cells with gamma-IFN.


In-the-bag intraocular lens placement via secondary capsulorhexis with radiofrequency diathermy in pediatric aphakic eyes.
Pediatric ophthalmologists increasingly recognize that the ideal site for intraocular lens (IOL) implantation is in the bag for aphakic eyes, but it is always very difficult via conventional technique. We conducted a prospective case series study to investigate the success rate and clinical outcomes of capsular bag reestablishment and in-the-bag IOL implantation via secondary capsulorhexis with radiofrequency diathermy (RFD) in pediatric aphakic eyes, in which twenty-two consecutive aphakic pediatric patients (43 aphakic eyes) enrolled in the Childhood Cataract Program of the Chinese Ministry of Health were included. The included children underwent either our novel technique for secondary IOL implantation (with RFD) or the conventional technique (with a bent needle or forceps), depending on the type of preoperative proliferative capsular bag present. In total, secondary capsulorhexis with RFD was successfully applied in 32 eyes (32/43, 74.4%, age 5.6±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved in 30 eyes (30/43, 70.0%), but in the remaining 2 eyes (2/32, 6.2%) the IOLs were implanted in the sulcus with a capsular bag that was too small. Secondary capsulorhexis with conventional technique was applied in the other 11 eyes (11/43, 25.6%, age 6.9±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved only in 3 eyes(3/43, 7.0%), and the IOLs were implanted in the sulcus in the remaining 8 eyes. A doughnut-like proliferative capsular bag with an extensive Soemmering ring (32/43, 74.4%) was the main success factor for secondary capsulorhexis with RFD, and a sufficient capsular bag size (33/43, 76.7%) was an additional factor in successful in-the-bag IOL implantation. In conclusion, RFD secondary capsulorhexis technique has 70% success rate in the capsular bag reestablishment and in-the-bag IOL implantation in pediatric aphakic eyes, particularly effective in cases with a doughnut-like, extensively proliferative Soemmering ring.


Detection of genes encoding cholera toxin (CT), zonula occludens toxin (ZOT), accessory cholera enterotoxin (ACE) and heat-stable enterotoxin (ST) in Vibrio mimicus clinical strains.
A total of 51 clinical strains of Vibrio mimicus were searched for the presence of virulence-associated genes, like ctx, zot or ace genes which locate in "cholera virulence cassette," and the st gene by polymerase chain reaction. Moreover, the pathological potential of each clinical strain was also examined by rabbit ileal loop (RIL). Three strains showed to have the ctx gene, of which only one strain was zot gene-positive. Meanwhile, one other strain was zot+ but ctx-. All of these four strains were found to have the ace gene and to belong to serogroup O115. Nine strains showed to carry the st gene. However, none of these ST-gene-positive strains was indicated to contain the genes located in the "cholera virulence cassette." It is of interest to note that all of the RIL-positive and/or virulence gene-positive strains were restricted to three serogroups, O20, O41 and O115. These results suggest a significant association between O antigens and enterotoxic activities in V. mimicus clinical strains, and clearly demonstrate multifactorial virulence potentials of this human pathogen.


GABAB receptors in the NTS mediate the inhibitory effect of trigeminal nociceptive inputs on parasympathetic reflex vasodilation in the rat masseter muscle.
The present study was designed to examine whether trigeminal nociceptive inputs are involved in the modulation of parasympathetic reflex vasodilation in the jaw muscles. This was accomplished by investigating the effects of noxious stimulation to the orofacial area with capsaicin, and by microinjecting GABA(A) and GABA(B) receptor agonists or antagonists into the nucleus of the solitary tract (NTS), on masseter hemodynamics in urethane-anesthetized rats. Electrical stimulation of the central cut end of the cervical vagus nerve (cVN) in sympathectomized animals bilaterally increased blood flow in the masseter muscle (MBF). Increases in MBF evoked by cVN stimulation were markedly reduced following injection of capsaicin into the anterior tongue in the distribution of the lingual nerve or lower lip, but not when injected into the skin of the dorsum of the foot. Intravenous administration of either phentolamine or propranolol had no effect on the inhibitory effects of capsaicin injection on the increases of MBF evoked by cVN stimulation, which were largely abolished by microinjecting the GABA(B) receptor agonist baclofen into the NTS. Microinjection of the GABA(B) receptor antagonist CGP-35348 into the NTS markedly attenuated the capsaicin-induced inhibition of MBF increase evoked by cVN stimulation, while microinjection of the GABA(A) receptor antagonist bicuculline did not. Our results indicate that trigeminal nociceptive inputs inhibit vagal-parasympathetic reflex vasodilation in the masseter muscle and suggest that the activation of GABA(B) rather than GABA(A) receptors underlies the observed inhibition in the NTS.


Towards an IoT-based upper limb rehabilitation assessment system.
Rehabilitation of stroke survivors has been increasing in importance in recent years with increase in the occurrence of stroke. However, current clinical classification assessment is time-consuming while the result is not accurate and varies across physicians. This paper introduces an IoT-based upper limb rehabilitation assessment system for stroke survivors based on wireless sensing sub-system, data cloud, computing cloud and software based on Android platform. The system can automatically perform objective assessment. It is designed for home rehabilitation as well as for the concept of graded rehabilitation therapy.


Implementation and evaluation of an undergraduate Sociocultural Medicine Program.
To demonstrate an effective model for designing, implementing, and evaluating the Sociocultural Medicine Program (SMP), part of a comprehensive sociocultural medicine curriculum at the University of Michigan Medical School. This study followed a cross-sectional, pre- and post-intervention survey design. A total of 167 medical students completed a measure of attitudes toward sociocultural issues in medicine prior to and following participation in the SMP. Students' attitudes were assessed in the domains of "exposure to sociocultural issues," "sociocultural factors in clinical scenarios," and "sociocultural background in patient/physician/health status issues." Paired t-tests of the pre- and post-intervention responses revealed significant positive changes for items in the domain of exposure to sociocultural issues in medicine: experience with sociocultural issues in a clinical setting (p <.01), understanding of relationship among sociocultural background, health, and medicine (p <.001), and importance of sociocultural background in students' future patient populations (p <.01). Significant changes were also found for the impact of sociocultural background in patient/physician/health status issues: physician-patient relationship (p <.001) and patients' health behavior (p <.001). The SMP had a significant educational impact on students' attitudes towards sociocultural issues in medicine. Students reported greater exposure to these issues conceptually and clinically, and greater influence of sociocultural factors in patients' behaviors and patient- physician relationships. Critical components of this SMP were faculty development, multiple teaching approaches, and pre- and post-intervention evaluation.


Autoinhibitory regulation of p73 by Delta Np73 to modulate cell survival and death through a p73-specific target element within the Delta Np73 promoter.
p73 is a p53-related tumor suppressor but is also induced by oncogene products such as E2F-1, raising a question as to whether p73 is a tumor suppressor gene or oncogene. Unlike p53, p73 has several variants, including Delta Np73, which lacks the NH(2)-terminal transactivation domain. Although, in developing neurons, Delta Np73 is expressed abundantly and seems to inhibit the proapoptotic function of p53, the role of p73 and Delta Np73 and their regulatory mechanism in cell growth and differentiation are poorly understood. Here we report that p73, but not p53, directly activates the transcription of endogenous Delta Np73 by binding to the p73-specific target element located at positions -76 to -57 within the Delta Np73 promoter region. The activation of Delta Np73 promoter by p63 was marginal. Delta Np73 was associated with p73 alpha, p73 beta, and p53, as demonstrated by immunoprecipitation assays, and inhibited their transactivation activities when we used reporters of Mdm2, Bax, or Delta Np73 itself in SAOS-2 cells. Furthermore, induction or overexpression of Delta Np73 promoted cell survival by competing with p53 and p73 itself. Thus, our results suggest that the negative feedback regulation of p73 by its target Delta Np73 is a novel autoregulatory system for modulating cell survival and death.


Doping of polyaniline with 6-cyano-2-naphthol.
The conductivity of polyaniline (PANI) is ascribed to its emeraldine salt (PANI-ES), which is formed by protonation of its emeraldine base (PANI-EB) by acids. Generally, mineral acids are used for this purpose, but the use of dopants and additives to maintain the required acidity provides an alternative method to the preparation of PANI-ES. The present work attempts to achieve the protonation by the use of a weak organic acid, namely, 6-cyano-2-naphthol (6CN2), which is generally used as a superphotoacid, as its excited state pKa is significantly smaller than its ground state pKa. The question here is if the protonation of the aniline moieties in PANI takes place and if it does, whether it takes place by dissociation of the ground state or the excited state of 6CN2. Room temperature conductance measurements were carried out to see the effect of doping. The formation of PANI-ES from PANI-EB has been monitored by UV-vis spectrophotometry. When a polar counterion is inserted into the polymer matrix, it changes the environment of the nearby chains by introducing defects, reorganization of charges as a result of interaction with the polymer. Morphological investigation was done using optical microscopy, field emission gun scanning electron microscopy (FEGSEM), and field emission gun transmission electron microscopy FEGTEM. The influence of 6CN2 on the crystallinity of the polymer was determined by X-ray diffraction (XRD).


Catheter-related bacteraemia in haemodialysis patients with HIV infection.
Tunnelled catheters are used for dialysis in over 25% of haemodialysis (HD) patients and are a major risk factor for bacteraemia. HIV-positive patients may be at particularly increased risk of catheter-related bacteraemia (CRB) due to their immunocompromised state. The present case-controlled study compared catheter-related bacteraemia with HIV-positive and HIV-negative haemodialysis patients. Using a prospective computerized vascular access database, we identified 33 HIV-positive haemodialysis patients who had a tunneled dialysis catheter placed during a 6.5-year period. Their catheter outcomes were compared with those observed in 55 age-, sex- and access date-matched control haemodialysis patients. The two groups were similar in terms of age, sex, diabetes, hypertension and peripheral vascular disease, but the HIV patients were more likely to be black (94 vs 76%, P=0.03). CRB occurred in 52% of the HIV patients and 49% of the controls (P=0.83). The median infection-free catheter survival was similar in HIV-positive and negative patients (165 vs 119 days, P=0.12). Among patients with CRB, the likelihood of a Gram-negative infection was similar in both groups (18 vs 30%, P=0.37). However, polymicrobial CRB was more likely in HIV patients (41 vs 15%, P=0.049). HIV-positive patients were more likely to be hospitalized for treatment of CRB than HIV-negative patients (29 vs 7%, P=0.05). CRB is equally likely in HIV-positive and control haemodialysis patients. However, CRB is likely to be more severe in HIV-positive patients, as judged from the greater likelihood of polymicrobial infection and of hospitalization.


High-dose intensity pulse interleukin-2 with famotidine in metastatic kidney cancer.
Lymphokine-activated killer cell (LAK) activity against tumor cell lines may be induced by intravenous (i.v.) interleukin-2 (IL-2). Daily short infusions (pulses) have been developed to decrease toxicity while maintaining the anticancer activity of this agent against kidney cancer. The anthihistamine, famotidine, may increase IL-2 uptake by the IL-2 receptor on lymphocytes. We have treated 12 patients with metastatic kidney cancer, using pulse IL-2 (18 million IU/M(2) i.v.) over 15-30 minutes, preceded by famotidine (20 mg I.V. daily for 5 days) on an oncology inpatient unit. Cycles were repeated every 3 weeks until disease progression. Patient characteristics were as follows: 9 males with a median age of 66 years (range, 48-74), and median Eastern Cooperative Oncology Group performance status of 1; common metastatic sites included in the lungs 9 and lymph nodes 3. Median number of cycles received was 2 (range, 1-5). The most common toxicities were fever, rigors, and hypomagnesemia. Two (2) patients had partial responses (17% response rate). Responses occurred in the liver (11.5 months) and lung, pleura, and lymph nodes (3 months). Pulse IL-2 with famotidine shows activity in kidney cancer.


Estimations of bone mineral density defined osteoporosis prevalence and cutpoint T-score for defining osteoporosis among older Chinese population: a framework based on relative fragility fracture risks.
This study estimated the bone mineral density (BMD) defined osteoporosis prevalence of Chinese women and Chinese men aged ≥50 years. The estimation was based on the 1994 WHO definition of osteoporosis and two assumptions: (I) fragility fracture (FF) risk among older Chinese is half of that of older US Caucasians; (II) FF risk among older Chinese men is half of that of older Chinese women. In addition, we also consider the FF risk among older Chinese is close to those of American Blacks. We estimated that the osteoporosis prevalence based on lumbar BMD, femoral neck BMD, total hip BMD would be 15.8%, 20.4%, and 15.2% for US Caucasian women, 6.7%, 7.8%, and 7.9% for US black women, 7.5%, 7.5%, and 6.7% for Chinese women, 1.8%, 5.7%, and 3.3% for US black men, and 2.0%, 3.8%, and 3.4% for Chinese men. To satisfy the above estimates of osteoporosis prevalence for the Chinese population, in addition to using a local reference database, we suggest that the T-score cutpoints for defining osteopenia and osteoporosis among older Chinese should be adjusted from the conventional WHO thresholds of -2.5 and -1.0. Our suggested revised cutpoint T-score for defining osteoporosis described in this article will be more in line with the original WHO definition and will allow a more meaningful international comparison of disease burden.


A study of the potential effect of yellow mealworm (Tenebrio molitor) substitution for fish meal on growth, immune and antioxidant capacity in juvenile largemouth bass (Micropterus salmoides).
This study aimed to evaluate the effects of partial replacement of fish meal (FM) with yellow mealworm (Tenebrio molitor, TM) on the growth performance, food utilization and intestinal immune response of juvenile largemouth bass (Micropterus salmoides). Seven diets containing increasing levels of TM (FM substitution) were designed (approximately 0% (0%), 4% (11.1%), 8.1% (22.2%), 12.2% (33.3%), 16.3% (44.4%), 20.4% (55.5%), and 24.5% (66.6%), designated TM0, TM11, TM22, TM33, TM44, TM55, and TM66, respectively). 420 fish were randomly selected and placed in 21 cages (1 m*1 m*1 m, 7 treatments for triplicate, 20 fish per cage). Fish (initial weight 6.25 ± 0.03 g) were fed seven isonitrogenous (47%) and isocaloric (19 MJ kg-1) diets to satiety twice daily for 8 weeks. Compared to the control group (TM0), TM11 showed no significant difference in the weight gain rate (WGR), specific growth rate (SGR) or feed conversion ratio (FCR), while all other TM inclusion groups presented different degrees of decline. There was no significant difference in the whole-body composition among all groups (P > 0.05). Plasma total protein (TP), triglyceride (TG) and albumin (ALB) contents were significantly decreased in TM55 and TM66 (P < 0.05). The highest plasma aspartate transaminase (AST) activity was observed in TM66 (P < 0.05). TM33, TM44 and TM55 showed the lowest activities of plasma alanine amiotransferase (ALT) and alkaline phosphatase (ALP) (P < 0.05). Moreover, increased mRNA levels of superoxide dismutase (SOD) and catalase (CAT) were measured in the TM11 to TM55 groups, while intestinal SOD activity peaked in TM11 (P < 0.05). With the exception of TM11, the other TM inclusion groups showed significant inhibition of the relative expression of RelA, C3 and TNF-α (P < 0.05). All experimental groups exhibited lower expression of IL-10 than TM0 (P < 0.05). The TM11 group showed significantly upregulated expression of IL-1β and TGF-β (P < 0.05). In addition, TLR2 expression was increased in TM11 and TM22 (P < 0.05). Considering enzyme activities and immune-related gene expression, TM supplementation levels should not exceed 4% (TM11).


Utilization of cumulative antibiograms for public health surveillance: Trends in Escherichia coli and Klebsiella pneumoniae susceptibility, Massachusetts, 2008-2018.
Antimicrobial resistance is an urgent public health threat. Identifying trends in antimicrobial susceptibility can inform public health policy at the state and local levels. To determine the ability of statewide antibiogram aggregation for public health surveillance to identify changes in antimicrobial resistance trends. Facility-level trend analysis. Crude and adjusted trend analyses of the susceptibility of Escherichia coli and Klebsiella pneumoniae to particular antibiotics, as reported by aggregated antibiograms, were examined from 2008 through 2018. Multivariable regression analyses via generalized linear mixed models were used to examine associations between hospital characteristics and trends of E. coli and K. pneumoniae susceptibility to ciprofloxacin and ceftriaxone. E. coli and K. pneumoniae showed inverse trends in drug susceptibility over time. K. pneumoniae susceptibility to fluoroquinolones increased by 5% between 2008 and 2018 (P < .05). In contrast, E. coli susceptibility declined during the same period to ceftriaxone (6%), gentamicin (4%), and fluoroquinolones (4%) (P < .05). When compared to Boston hospitals, E. coli isolates from hospitals in other regions had a >4% higher proportion of susceptibility to ciprofloxacin and a >3% higher proportion of susceptibility to ceftriaxone (P < .05). Isolates of K. pneumoniae had higher susceptibility to ciprofloxacin (>3%) and ceftriaxone (>1.5%) in all regions when compared to Boston hospitals (P < .05). Cumulative antibiograms can be used to monitor antimicrobial resistance, to discern regional and facility differences, and to detect changes in trends. Furthermore, because the number of years that hospitals contributed reports to the state-level aggregate had no significant influence on susceptibility trends, other states should not be discouraged by incomplete hospital compliance.


Britanin Ameliorates Cerebral Ischemia-Reperfusion Injury by Inducing the Nrf2 Protective Pathway.
Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new Nrf2 activators and test their neuronal protective activity both in vivo and in vitro. The herb-derived compound, Britanin, is a potent inducer of the Nrf2 system. Britanin can induce the expression of protective enzymes and reverse oxygen-glucose deprivation, followed by reperfusion (OGD-R)-induced neuronal injury in primary cortical neurons in vitro. Furthermore, the administration of Britanin significantly ameliorated middle cerebral artery occlusion-reperfusion (MCAO-R) insult in vivo. We report here the crystal structure of the complex of Britanin and the BTB domain of Keap1. Britanin selectively binds to a conserved cysteine residue, cysteine 151, of Keap1 and inhibits Keap1-mediated ubiquitination of Nrf2, leading to induction of the Nrf2 pathway. Britanin is a potent inducer of Nrf2. The complex crystal structure of Britanin and the BTB domain of Keap1 help clarify the mechanism of Nrf2 induction. Britanin was proven to protect primary cortical neurons against OGD-R-induced injury in an Nrf2-dependant way. Additionally, Britanin had excellent cerebroprotective effect in an MCAO-R model. Our results demonstrate that the natural product Britanin with potent Nrf2-activating and neural protective activities both in vitro and in vivo could be developed into a cerebroprotective therapeutic agent. Antioxid. Redox Signal. 27, 754-768.


A retrospective review of paclitaxel-associated gastrointestinal necrosis in patients with epithelial ovarian cancer.
Seven patients with gastrointestinal necrosis following paclitaxel chemotherapy are reported. Four of seven patients had platinum refractory disease, while 3/7 patients received primary paclitaxel therapy. Complications occurred 5 to 16 days following paclitaxel therapy. The most common clinical presentation was fever (7/7 patients), neutropenia (6/7 patients), and abdominal pain (6/7 patients). All seven patients developed gastrointestinal necrosis following the first cycle of paclitaxel chemotherapy. The exact mechanism by which this complication occurs is poorly understood. We postulate that gastrointestinal necrosis may be the result of a direct drug effect on the gastrointestinal epithelium and might involve a synergistic interaction between compromised bowel and paclitaxel-induced mitotic arrest. We observe that the incidence of gastrointestinal necrosis in patients with platinum refractory disease is 4 of 108 patients (3.7%). The incidence of this complication in patients receiving primary paclitaxel at our institution is 3 of approximately 128 patients (2.3%). Eighteen cases to date have been identified in the literature. A high index of suspicion of this complication should be considered for patients presenting with neutropenic fever and abdominal pain following paclitaxel chemotherapy.


Antifungal steroid glycoside from sea cucumber.
An antifungal steroid glycoside, holotoxin, has been isolated from the sea cucumber Stichopus japonicus (Selenka). In vitro, it exhibits high activity against various fungi, including vegetable pathogens, but has scarcely any activity against Gram-positive and Gram-negative bacteria and mycobacteria in vitro.


L-DOPA Oppositely Regulates Synaptic Strength and Spine Morphology in D1 and D2 Striatal Projection Neurons in Dyskinesia.
Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections. Dopamine depletion induced spine pruning in both types of MSNs, affecting mushroom and thin spines equally. Dopamine depletion also increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density remained reduced but the remaining spines were enlarged, with bigger heads and larger postsynaptic densities. These morphological changes were accompanied by facilitation of action potential firing triggered by synaptic inputs. In contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted in shortened postsynaptic densities. These changes in D2-MSNs correlated with a decrease in synaptic transmission. Our findings indicate that L-DOPA-induced dyskinesia is associated with abnormal spine morphology, modified synaptic transmission, and altered EPSP-spike coupling, with distinct effects in D1- and D2-MSNs.


Similarity and social interaction: when similarity fosters implicit behavior toward a stranger.
People interact more readily with someone whom they think they have something in common with. At a pedestrian crossing, confederates asked participants for the time and, in one condition, said she/he had the same watch as the participant. The amount of time that participants lingered near a confederate was used as the dependent variable. Participants in the similarity condition spent significantly more time near the confederate than when no similarity was manipulated. The results showed that similarity fosters implicit behavior, adding to the growing body of data on the positive effects of similarity and its role in social interaction.


Polystyrene-supported diarylprolinol ethers as highly efficient organocatalysts for Michael-type reactions.
α,α-Diphenylprolinol methyl- and trimethylsilyl ethers anchored onto a polystyrene resin have been prepared by a copper-catalyzed azide-alkyne cycloadditions (CuAAC). The catalytic activity and enantioselectivity displayed by the O-trimethylsilyl derivative are comparable to those exhibited by the best known homogeneous catalysts for the addition of aldehydes to nitroolefins and of malonates or nitromethane to α,β-unsaturated aldehydes. The combination of the catalytic unit, the triazole linker, and the polymeric matrix provides unprecedented substrate selectivity, in favor of linear, short-chain aldehydes, when the organocatalyzed reaction proceeds by an enamine mechanism. High versatility is noted in reactions that proceed via an iminium ion intermediate. The catalytic behavior of polystyrene-supported α,α-diphenylprolinol methyl ether was also evaluated in asymmetric Michael addition reactions. As a general trend, the CuAAC immobilization of diarylprolinol ethers onto insoluble polystyrene resins offers important operational advantages, such as high catalytic activity, easy recovery from the reaction mixture by simple filtration, and the possibility of extended reuse.


Flow cytometric analysis of tumor DNA profile related to response to treatment and survival in small-cell lung cancer.
Flow cytometric (FCM) analysis of tumor DNA ploidy and S-phase fraction (SPF) has been widely used to predict prognosis and treatment response in many malignant tumors, but rarely in small-cell lung cancer (SCLC). In the present study, tumor DNA ploidy and SPF were measured from paraffin-embedded tumor biopsy samples of 36 small-cell lung cancer patients treated with combination chemotherapy and radiotherapy. Aneuploidy was detected in 69% of the tumors. There was a statistically non-significant trend towards more aneuploidy among extensive disease (ED) patients as compared to patients with limited disease (LD): 80% versus 65%, respectively (p = 0.69). The mean SPF was 21.3% (+/-7.6) in patients with LD and 29.0% (+/-5.3) in patients with ED, the difference (7.6%) being statistically significant (p = 0.008, 95% CI for the difference 2.2-13.1). No significant differences was detected in the survival of aneuploid and diploid patients or patients with low (< or = 24.9%) and high (> 24.9%) SPF. Similarly, no significant difference was observed between aneuploid and diploid cases in relation to response to treatment or response duration. It is concluded that the difference detected in the SPF with LD and ED of SCLC may indicate the biological aggressiveness of extensive SCLC.


Method for the preparation of porous silica antireflection coatings varying in refractive index from 1.22 to 1.44.
Coatings of refractive index that vary between 1.22 and 1.44 were prepared from combinations of a colloidal silica suspension and a polysiloxane solution. The polysiloxane acted both as a binder and a filler for the colloidal silica particles. Increasing ratios gave coatings of lower porosity, hence higher refractive index, and better abrasion resistance. This variation in refractive index allowed highefficiency quarter-wave antireflection coatings to be prepared on substrates whose index varied from 1.45 to 2.1. The laser damage thresholds of all the coatings were >50 J/cm(2) at a wavelength of 1.06 microm with a 10-ns pulse length.


Investigation of an allergen adsorption on amine- and acid-terminated thiol layers: influence on their affinity to specific antibodies.
This work describes the controlled immobilization of a recognized allergen, beta-lactoglobulin, onto gold transducers with the aim of optimizing the elaboration of a biosensor directed against allergen-produced antibodies. This protein was immobilized on both amine- and acid-terminated thiol self-assembled monolayers, and the influence on its affinity to a specific IgG was investigated. For amine-terminated layers, the beta-lactoglobulin was immobilized via its surface acid functions implying an activation step with 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride/ester of N-hydroxysuccinimide (EDC-NHS). Conversely, the grafting on acid-terminated layer takes advantage of the accessible amine groups that react with the activated acidalkylthiols. The resulting layers of beta-lactoglobulin were then submitted to various concentrations of rabbit serum containing beta-lactoglobulin specific rabbit immunoglobulin (rIgG), and the antigen/antibody affinity was evaluated using modulated polarization-infrared absorption spectroscopy (PM-IRRAS) and Fourier transform surface plasmon resonance (FT-SPR). Even though for similar concentration, the amount of adsorbed beta-lactoglobulin was identical on both surfaces, atomic force microscopy (AFM) images showed a better dispersion for amine-terminated layers. Moreover, the affinity to specific IgG, estimated under static conditions by PM-IRRAS and under dynamic conditions by SPR, was different. Grafting beta-lactoglobulin via its acid groups gave an affinity constant 3 times higher than its immobilization via its amine groups despite the fact that the amount of accessible recognition sites appeared to be similar for both systems. This work underlines the importance of the involved chemical groups upon protein immobilization on their biological activity and will be essential for the construction of nondirect biosensors for detecting specific immunoglobulin E (IgE) of allergens.


Using Caffeine and Free Amino Acids To Enhance the Transepithelial Transport of Catechins in Caco-2 Cells.
Catechins are well-known to possess health-promoting functions. The interaction of the catechins with other components in tea could alter their absorption and efflux. This study investigated whether the absorption of catechins is affected by caffeine and amino acids using the Caco-2 monolayer cell model. We found that (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) were all actively effluxed. Co-transportation of EGCG, ECG, or EC with caffeine, theanine, serine, or glycine increased their apparent permeability coefficient [ Papp(AP-BL)] value by 3.42-5.40- fold, 1.19-5.75-fold, and 1.55-8.01-fold, respectively. Meanwhile, their efflux ratio values were significantly decreased. Moreover, the expression of multi-drug resistance protein 2 (MRP2) after 3 h of incubation with either 50 μM EGCG or 50 μM EC was elevated by 1.58- and 2.98-fold, respectively, while 50 μM ECG had no significantly effects. In addition, the expression of P-glycoprotein (P-gp) after treatment with either 50 μM EGCG, 50 μM ECG, or 50 μM EC was enhanced by 1.53-, 1.63-, and 1.80-fold, respectively. The addition of either caffeine or any one of the three amino acids decreased the expression of both MRP2 and P-gp induced by EGCG, and the expression of P-gp induced by ECG or EC also decreased. In contrast, only glycine decreased the expression of MRP2 induced by EC. Taken together, our data indicated that caffeine and theanine, glycine, or serine in tea might increase the absorption of catechins by the selectively suppressed expression of the efflux transporters induced by catechins.


[Antidiarrheal drugs for chronic diarrhea].
Chronic diarrhea can be caused by multiple disease entities. Basic diagnostic tests are required in order to administer specific therapies whenever possible. If no specific treatment can be used, a symptomatic management should be initiated in order to prevent massive electrolyte- and water losses. Substances that can be used are loperamide, cholestyramine, bulking agents, probiotics, anticholinergic agents and in severe cases opioids. If used properly these agents can be prescribed longterm with an acceptable side effect profile.


Targeting screening and treatment for latent tuberculosis infection towards asylum seekers from high-incidence countries - a model-based cost-effectiveness analysis.
Enhancing tuberculosis (TB) prevention and care in a post-COVID-19-pandemic phase will be essential to ensure progress towards global TB elimination. In low-burden countries, asylum seekers constitute an important high-risk group. TB frequently arises post-immigration due to the reactivation of latent TB infection (LTBI). Upon-entry screening for LTBI and TB preventive treatment (TPT) are considered worthwhile if targeted to asylum seekers from high-incidence countries who usually present with higher rates of LTBI. However, there is insufficient knowledge about optimal incidence thresholds above which introduction could be cost-effective. We aimed to estimate, among asylum seekers in Germany, the health impact and costs of upon-entry LTBI screening/TPT introduced at different thresholds of country-of-origin TB incidence. We sampled hypothetical cohorts of 30-45 thousand asylum seekers aged 15 to 34 years expected to arrive in Germany in 2022 from cohorts of first-time applicants observed in 2017-2019. We modelled LTBI prevalence as a function of country-of-origin TB incidence fitted to data from observational studies. We then used a probabilistic decision-analytic model to estimate health-system costs and quality-adjusted life years (QALYs) under interferon gamma release assay (IGRA)-based screening for LTBI and rifampicin-based TPT (daily, 4 months). Incremental cost-effectiveness ratios (ICERs) were calculated for scenarios of introducing LTBI screening/TPT at different incidence thresholds. We estimated that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5% (95% uncertainty interval: 14.2-21.6%) will be latently infected. Introducing LTBI screening/TPT above 250 per 100,000 country-of-origin TB incidence would gain 7.3 (2.7-14.8) QALYs at a cost of €51,000 (€18,000-€114,100) per QALY. Lowering the threshold to ≥200 would cost an incremental €53,300 (€19,100-€122,500) per additional QALY gained relative to the ≥250 threshold scenario; ICERs for the ≥150 and ≥ 100 thresholds were €55,900 (€20,200-€128,200) and €62,000 (€23,200-€142,000), respectively, using the next higher threshold as a reference, and considerably higher at thresholds below 100. LTBI screening and TPT among 15- to 34-year-old asylum seekers arriving in Germany could produce health benefits at reasonable additional cost (with respect to international benchmarks) if introduced at incidence thresholds ≥100. Empirical trials are needed to investigate the feasibility and effectiveness of this approach.


The winner takes it all: Event-related brain potentials reveal enhanced motivated attention toward athletes' nonverbal signals of leading.
Observers of sports can reliably estimate who is leading or trailing based on nonverbal cues. Most likely, this is due to an adaptive mechanism of detecting motivationally relevant signals such as high status, superiority, and dominance. We reasoned that the relevance of leading athletes should lead to a sustained attentional prioritization. To test this idea, we recorded electroencephalography while 45 participants saw brief stills of athletes and estimated whether they were leading or trailing. Based on these recordings, we assessed event-related potentials and focused on the late positive complex (LPC), a well-established signature of controlled attention to motivationally relevant visual stimuli. Confirming our expectation, we found that LPC amplitude was significantly enhanced for leading as compared to trailing athletes. Moreover, this modulation was significantly related to behavioral performance on the score-estimation task. The present data suggest that subtle cues related to athletic supremacy are reliably differentiated in the human brain, involving a strong attentional orienting toward leading athletes. This mechanism might be part of an adaptive cognitive strategy that guides human social behavior.


Characteristics of relief phase holograms recorded in photoresists.
Recording of relief phase holograms in Shipley AZ-1350 positive photoresist is investigated in this report. It is found that the use of Shipley AZ-303 developer with Shipley AZ-1350 photoresist relieves the material nonlinearity usually associated with photoresists, thereby allowing higher image readout efficiencies. The use of Shipley AZ-303 developer also provides an increase in material sensitivity. A theoretical model for positive photoresist exposure characteristics is developed and verified by empirical results. Using Shipley AZ-303 developer, a design procedure for recording useful (i.e., acceptable SNR > 25 dB, high efficiency ~3-5%, exposure sensitivity ~ a few mJ.cm(-2)) relief phase holograms in Shipley AZ-1350 positive photoresist is synthesized.


Time for the economist and the surgeon to rub shoulders.
The NHS is no longer in a position to simply buy itself out of trouble writes Brendan Devlin, consultant surgeon, North Tees General Hospital. In this article he urges doctors to involve themselves in the financial planning of the service and says that society expects clinicians to spend money wisely and to act as guardians of the taxpayer.


Glycomacrocycle-Based Azobenzene Derivatives as Chiral Dopants for Photoresponsive Cholesteric Liquid Crystals.
We demonstrate photoresponsive cholesteric liquid crystals (CLCs) doped with glycomacrocyclic azobenzene derivatives, which exhibit large conformational changes, providing dynamic control of helical superstructures in response to a light stimulus. An unprecedented shortening of the helical pitch length and the empowerment of helical twisting power up to 500% are observed upon trans (E) to cis (Z) photoisomerization. Light-driven dynamic helix twisting and untwisting behavior affords the first example of glycomacrocyclic azobenzene-based CLCs, which can drive the mechanical movement of micro-objects. Two modes of rotation-two-directional or one-directional rotational motion (crankshaft mode)-are realized. In particular, the latter mode based on the reversible cholesteric texture transition between homogeneous stripes and focal conics leads to the accumulation of the rotation angles achieving the amplified mechanical movements.


Hereditary Coproporphyria Associated with the Q306X Mutation in the Coproporphyrin Oxidase Gene Presenting with Acute Ataxia.
Hereditary coproporphyria (HCPO) is a low-penetrance, autosomal dominant, acute hepatic porphyria characterized by the overproduction and excretion of coproporphyrin. The most common neurological manifestations of this entity include peripheral, predominantly motor dysfunction, and central nervous system dysfunction. Ataxia associated with HCPO has not been reported previously. The aim of this article is to report a patient with HCPO presenting with acute ataxia. We describe a 44-year-old patient presenting clinically with acute ataxia who was diagnosed with HCPO; mutations were analyzed in the coproporphyrin-oxidase III (CPOX) gene in the patient and in six asymptomatic first-degree relatives. The patient was heterozygous for a mutation causing the amino acid exchange Q306X in the CPOX gene. No relatives carried the same or another mutation in the CPOX gene. HCPO should be considered in the differential diagnosis for patients presenting with ataxia.


Successful Treatment With Total Skin Electron Beam Therapy in a Child With Isolated Cutaneous Relapsed AML.
A 9-year-old girl diagnosed with acute myeloblastic leukemia M4 developed isolated cutaneous relapse. She was given chemotherapy including idarubicin, fludarabine, and cytarabine. Although she developed very severe pancytopenia, increase in the number and size of the lesions was seen. Total skin electron beam therapy was applied to the skin lesions for a total of 18 Gy. All lesions responded to total skin electron beam therapy, some of them completely disappeared. After resolution of the skin findings, she underwent bone marrow transplantation from her matched brother. Twenty-six months after hematopoietic stem cell transplantation she is alive without any event.


Generation of Frizzled10-Cre transgenic mouse line: a useful tool for the study of dorsal telencephalic development.
Wnt signaling plays an important role in regulating cortical and hippocampal development, but many of the other molecular mechanisms underlying dorsal telencephalic development are largely unknown. We are taking advantage of the highly regionalized expression patterns of signaling components of the Wnt pathway to generate new mouse lines that will be useful for studying forebrain development. Here, we describe a transgenic mouse line where Cre is driven by the promoter of the Wnt receptor, Frizzled10. In these mice, Cre activity is mainly detected in the dorsal telencephalon during development and is confined to the pyramidal cell fields in the adult hippocampus. The Cre recombinase has very high efficiency when assayed by crossing the transgenic line with the ROSA26 reporter line. Thus, this Cre line will be useful for the study of dorsal telencephalic development and conditional inactivation of target genes in the cortex and hippocampus.


Signaling to NF-kappaB.
The transcription factor NF-kappaB has been the focus of intense investigation for nearly two decades. Over this period, considerable progress has been made in determining the function and regulation of NF-kappaB, although there are nuances in this important signaling pathway that still remain to be understood. The challenge now is to reconcile the regulatory complexity in this pathway with the complexity of responses in which NF-kappaB family members play important roles. In this review, we provide an overview of established NF-kappaB signaling pathways with focus on the current state of research into the mechanisms that regulate IKK activation and NF-kappaB transcriptional activity.


Signaling Dynamics of TSHR-Specific CAR-T Cells Revealed by FRET-Based Biosensors.
Although most patients with thyroid cancers have good prognosis and long-term survival, some patients are refractory to traditional therapeutic approaches and face a high risk of mortality. CAR-T therapy provides an attractive strategy to treat these patients. Considering the limited expression in thyroid tissues, thyroid-stimulating hormone receptor (TSHR) has been considered as a promising candidate as CAR-T target. However, it is still a challenge to find the optimal CAR design for the treatment of thyroid cancers. Dynamic signaling cascade is initiated by CAR molecules during CAR-T cell activation. The development of FRET-based biosensors enables us to detect the signaling dynamics of key kinases during CAR-T cell activation with high spatiotemporal resolution. Here using the ZAP70 and ERK biosensors, we visualized the dynamics of ZAP70 and ERK activities in TSHR-specific CAR-T cells upon antigen stimulation. We first constructed several TSHR-targeting CARs for the treatment of advanced thyroid cancers. The TSHR CAR-T cells with CD28 or 4-1BB co-stimulatory signaling domains exhibited potent cytotoxicity in vitro. By FRET imaging, we observed rapid increase of ZAP70 and ERK activities in TSHR CAR-T cells upon target cell binding. Even though CD28-based CAR-T cells had similar ZAP70 activation dynamics as 4-1BB-based CAR-T cells, they displayed slightly enhanced ERK activation, which may contribute to their faster anti-tumor kinetics in vivo. These results demonstrated the efficacy of TSHR CAR-T cells to treat advanced thyroid cancers. Our study indicated the potential of applying FRET biosensors to optimize the design of CAR for effective CAR-T therapy.


Interspecies Correlations between Human and Mouse NR2E3-Associated Recessive Disease.
NR2E3-associated recessive disease in humans is historically defined by congenital night blinding retinopathy, characterized by an initial increase in short-wavelength (S)-cone sensitivity and progressive loss of rod and cone function. The retinal degeneration 7 (rd7) murine model, harboring a recessive mutation in the mouse ortholog of NR2E3, has been a well-studied disease model and recently evaluated as a therapeutic model for NR2E3-associated retinal degenerations. This study aims to draw parallels between human and mouse NR2E3-related disease through examination of spectral domain optical coherence tomography (SD-OCT) imaging between different stage of human disease and its murine counterpart. We propose that SD-OCT is a useful non-invasive diagnostic tool to compare human clinical dystrophy presentation with that of the rd7 mouse and make inference that may be of therapeutically relevance. Additionally, a longitudinal assessment of rd7 disease progression, utilizing available clinical data from our patients as well as extensive retrospective analysis of visual acuity data from published cases of human NR2E3-related disease, was curated to identify further valuable correlates between human and mouse Nr2e3 disease. Results of this study validate the slow progression of NR2E3-associated disease in humans and the rd7 mice and identify SD-OCT characteristics in patients at or near the vascular arcades that correlate well with the whorls and rosettes that are seen also in the rd7 mouse and point to imaging features that appear to be associated with better preserved S-cone mediated retinal function. The correlation of histological findings between rd7 mice and human imaging provides a solid foundation for diagnostic use of pathophysiological and prognostic information to further define characteristics and a relevant timeline for therapeutic intervention in the field of NR2E3-associated retinopathies.


Clinical trials of the past decade in the management of chronic kidney disease.
The three main causes of Chronic Kidney Diseases [CKD] are diabetes mellitus, chronic glomerulonephritis and hypertension. CKD is an increasing burden in the community as more patients fall prey to kidney failure. Both dialysis and renal transplantation are expensive modalities of treatment for end stage renal failure [ESRF]. Through the years many clinical trials have been performed to retard the progression of CKD to ESRF. Most of the trials focus on three main strategies which aim at renal retardation, namely, control of hypertension, treatment of proteinuria and control of hypercholesterolaemia. More recently, investigators have been exploring the role of high dose ARBs as well as the use of Aliskiren, a renin inhibitor. Early therapeutic intervention is necessary as it will contribute to better chances of minimising glomerular damage and in the case of some, even lead to the improvement of renal function with regression of glomerulosclerosis.


Biogenesis and iron-dependency of ribosomal RNA hydroxylation.
Post-transcriptional modifications of ribosomal RNAs (rRNAs) are involved in ribosome biogenesis and fine-tuning of translation. 5-Hydroxycytidine (ho5C), a modification of unknown biogenesis and function, is present at position 2501 of Escherichia coli 23S rRNA. We conducted a genome-wide screen in E. coli to identify genes required for ho5C2501 formation, and found a previously-uncharacterized gene, ydcP (renamed rlhA), iron-sulfur cluster (isc) genes, and a series of genes responsible for prephenate biosynthesis, indicating that iron-sulfur clusters and prephenate are required for ho5C2501 formation. RlhA interacted with precursors of the 50S ribosomal subunit, suggesting that this protein is directly involved in formation of ho5C2501. RlhA belongs to a family of enzymes with an uncharacterized peptidase U32 motif and conserved Cys residues in the C-terminal region. These elements were essential for ho5C2501 formation. We also found that the frequency of ho5C2501 is modulated by environmental iron concentration. Together, our results reveal a novel biosynthetic pathway for RNA hydroxylation and its response to iron.


Chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer.
Laryngeal preservation is a challenge for the treatment of advanced hypopharyngeal cancer. The objective of this study is to evaluate the results of chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer at a single institute and the impact of treatment factors on prognosis. The study population consisted of 42 consecutive patients with resectable stage III-IV hypopharyngeal cancer. Patients with T4b tumor, synchronous primary cancer or those treated palliatively were excluded. Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) was performed in 32 (76.2%) patients, whereas primary CCRT was done in the other 10 (23.8%). Patients were grouped according to the dose intensity of chemotherapy and total dose of radiotherapy (RT). Grade 3-4 toxicities occurred mostly during CCRT. Thirty-five (83.3%) patients received an optimum dose of cisplatin (CT-optimum), 27 (64.3%) received an optimum dose of RT-optimum and 26 (61.9%) received optimum doses of both (CRT-optimum). CT- and RT-optimum both correlated significantly with better disease-free survival (DFS) (P < 0.001 and = 0.003), overall survival (OS) (P < 0.001 and = 0.004) and laryngeal preservation survival (LPS) (P = 0.01 and 0.04). The 3-year DFS, OS and LPS for CRT-optimum patients were 48.1, 50.0 and 45.6%, respectively. Achievement of optimum treatment dose remains challenging in chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer. Intensive patient care and monitoring by experienced multi-disciplinary teamwork are mandatory. The criteria for selecting patients who will respond to and complete the treatment remain key issues for future investigation.


God changed their lives: the value of religion in the elderly.
A descriptive phenomenological study of important life experiences of elderly Christians in Taiwan was conducted to explore how religion influences their lives. Three themes emerged from the responses of participants, offering insight into how religious beliefs impact the elderly.


Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats.
The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73mg AMM/kg body weight (BW), vehicle, or 100mg ATR/kg BW positive control, on gestation days 15-19. Preputial separation was significantly delayed in 0.87 mg and 8.73mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.


Critical size for the observation of quantum confinement in optically excited gold clusters.
We present a systematic study of optical properties of a series of hexanethiolate-capped Au clusters of varying sizes using femtosecond transient absorption, time-resolved fluorescence, and two-photon absorption cross-sectional measurements. An abrupt change in optical properties and their trends has been found at the 2.2 nm size. Displacively excited vibrations with a period of 450 fs have been detected in the transient absorption signal for smaller clusters < or = 2.2 nm. These results strongly suggest an emerging optical gap between the highest occupied and lowest unoccupied orbitals in the narrow size range at 2.2 nm.


Symmetric hydrogen bonding in dimethylammonium hydrogen diphenyldiphosphonate.
In the title compound, C2H8N+.C12H11O5P2-, pairs of hydrogen diphenyldiphosphonate anions form dimers across a twofold axis, with two symmetric O...H...O hydrogen bonds [O...O = 2.406 (3) and 2.418 (3) A]. The 12-membered ring thus formed has crystallographic 2 and quasi-222 symmetry. Cations on either side of the ring form N-H...O hydrogen bonds to the four extraannular O atoms, with N...O distances of 2.765 (2) and 2.748 (3) A.


Different effect of resveratrol to induction of apoptosis depending on the type of human cancer cells.
The effect of resveratrol on various human cancer cells was investigated with special focus on apoptotic cell death, in an attempt to further characterize its mechanism of action. There were great differences in the anti-viability effect of resveratrol between different types of human cancer cells. While the inhibition of cell viability by resveratrol was marked in U937 and MOLT-4 leukemia cells, resveratrol moderately inhibited cell viability in MCF-7 breast, HepG2 liver, and A549 lung cancer cells, and the effect was slight on cell viability in Caco-2, HCT116, and SW480 colon cancer cells. Following resveratrol treatment, U937 and MOLT-4 markedly increased the population of late apoptotic cells but MCF-7 and HepG2 underwent apoptosis with an increased population of early apoptosis, and resveratrol-induced DNA fragmentation was observed only in leukemic cells. Activation of sirtuin 1 and adenosine-monophosphate-activated protein kinase was not responsible for resveratrol-induced cancer cell death. Instead, resveratrol significantly reduced Akt activation with the downregulation of H-Ras, resulting in facilitation of Bax translocation to mitochondria in leukemic cells. This study suggests that resveratrol can induce apoptotic cell death in human leukemic cells to a greater extent than in human solid tumor cells via reducing Akt activation due to Ras downregulation.


Marinobacter segnicrescens sp. nov., a moderate halophile isolated from benthic sediment of the South China Sea.
A Gram-negative, motile, non-spore-forming and moderately halophilic ellipsoid-shaped marine coccobacillus, designated strain SS011B1-4(T), was isolated from benthic sediment of the South China Sea. Optimum growth occurred at 30-37 degrees C, pH 7.5-8.0 and 4-8 % (w/v) NaCl. Strain SS011B1-4(T) utilized a variety of organic substrates as sole carbon sources, but did not utilize toluene, n-tetradecane or crude oil. Strain SS011B1-4(T) had ubiquinone-9 as the major respiratory quinone and C(18 : 1)omega9c, C(16 : 0) and C(12 : 0) 3-OH as the predominant fatty acids. The genomic DNA G+C content was 62.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SS011B1-4(T) belonged to the genus Marinobacter of the Gammaproteobacteria. The results of the phenotypic, phylogenetic and genomic analyses revealed that strain SS011B1-4(T) represents a novel species of the genus Marinobacter. The name Marinobacter segnicrescens sp. nov. is therefore proposed, with strain SS011B1-4(T) (=LMG 23928(T)=CGMCC 1.6489(T)) as the type strain.


Pavoninins: shark-repelling ichthyotoxins from the defense secretion of the pacific sole.
A series of ichthyotoxic and hemolytic steroid aminoglycosides, pavoninins-1, to -6, has been isolated from the defense secretion of the sole Pardachirus pavoninus, and their respective chemical structures have been established by spectroscopic studies and chemical conversions. The pavoninins exert repellent activity against sharks and are considered to be the factors responsible for the predator-repelling property of the sole.


The future of pulmonary function testing.
The pulmonary function lab of today is heavily focused on describing pathophysiology and quantifying the extent of disease. As we move forward, it is important that the results of pulmonary function tests go beyond this and be linked to important outcomes that truly affect clinical decision making. To get there, improvements in device performance are required, high quality technicians are critical, and properly trained interpreting clinicians with good reference standards are mandatory. Moreover, as accessibility to these tests is increased, it is important that quality metrics remain intact. There is a wide array of novel tests that might be performed by pulmonary function labs in the future. These range from modification of current technologies to brand new technologies that are still in early development. Examples include exhaled breath analysis, sophisticated analyses of lung mechanics and gas exchange, cardiac and tissue oxygenation assessments, and imaging technologies. Adoption of any new technology will require, even more than today, clear evidence that the new technology is a real adjunct to clinical decision making.


Translating comparative effectiveness research into clinical practice: the UK experience.
Comparative effectiveness research (CER) is not new but its potential to improve the effectiveness of healthcare has not yet been exploited in the US. Other countries such as the UK have more experience of this. Key points of the UK experience are summarized here and some possible pointers for the US are drawn. These include the following: how to go beyond the evidence and apply judgements to make recommendations with authority and in a timely manner; how to implement these recommendations; how to identify suitable topics; and how to be open and transparently fair to all stakeholders. The quality of the science of CER is key but this needs developing, and not just in biomedical or statistical terms but also in how to understand public expectations, and how to implement its recommendations. A key issue is the role of health economics, which seems to have been marginalized by the CER legislation, but perhaps this is more apparent than real. Clearly this is a matter for much further debate. It is hard to see how CER can deliver its potential without active consideration of both benefits and costs. Although other countries have more experience of this than does the US, the context for such work is always very specific and the US will have to find its own way, while trying to avoid some of the errors made elsewhere.


Statistical Properties of the Nonlinear Stage of Modulation Instability in Fiber Optics.
We present an optical fiber experiment in which we examine the space-time evolution of a modulationally unstable plane wave initially perturbed by a small noise. Using a recirculating fiber loop as an experimental platform, we report the single-shot observation of the noise-driven development of breather structures from the early stage to the long-term evolution of modulation instability. Performing single-point statistical analysis of optical power recorded in the experiments, we observe decaying oscillations of the second-order moment together with the exponential distribution in the long-term evolution, as predicted by Agafontsev and Zakharov [Nonlinearity 28, 2791 (2015).NONLE50951-771510.1088/0951-7715/28/8/2791]. Finally, we demonstrate experimentally and numerically that the autocorrelation of the optical power g^{(2)}(τ) exhibits some unique oscillatory features typifying the nonlinear stage of the noise-driven modulation instability and of integrable turbulence.


Fraser syndrome in three consecutive siblings.
Fraser syndrome (FS) is a rare disorder characterized by a combination of acrofacial and urogenital malformations with or without cryptophthalmos. We report a newborn and its two elder siblings who had multiple congenital anomalies and clinico-radiological features consistent with FS.


Co-expression of Triosephosphate Isomerase, Fructose-1, 6-bisphosphate Aldolase and Fructose-1, 6-bisphosphatase in E.coli.
To establish a way to control or to decrease the daily increasing concentration of atmospheric CO(2), metabolically engineering Cyanobacteria was taken for the improvement of its efficiency of photosynthetic CO(2) fixation. As a preliminary stage of this study, three genes coding for three important Calvin cycle enzymes, i.e. triosephosphate isomerase (TPI), fructose-1, 6-bisphosphate aldolase(FBP aldolase),and fructose-1, 6-bisphosphatase(FBPase), respectively, have been cloned into one plasmid, pTrcFAT, which is controlled by promoter trc. Successful co-transcriptional expression of these three genes resulted inhigh yields of these enzymes under the induction of 0.25 mmol/L IPTG. Bioassay showed that the expressed enzymes from one liter of culture could directly catalyze DHAP conversion into 700 &mgr;mol of fructose-6-phosphate (F-6-P) per one minute. Furthermore, in order to introduce the three genes co-expression system into Cyanobacteria, a shuttle plasmid between E.coli and Cyanobacteria was constructed using plasmid pTrcFAT and a shuttle vector pDC-8, forming ashuttle plasmid pDCFAT-2 containing a dimer of the three genes co-expression operator. Successful co-expression in E.coli of pDCFAT-2 with higher full activity has been obtained. This shuttle was used to transform of Cyanobacteria Synechococcus sp. PCC 7942, and a few positive colonies were obtained.


Patterns of smoking during pregnancy in Canterbury.
To examine the prevalence and patterns of smoking in pregnancy with the object of improving smokefree programmes in the region. A postal questionnaire on smoking in pregnancy was sent to all 1916 mothers giving singleton births in the Canterbury region over a five month period. There was a 71.7% response rate, however, smokers were significantly under represented. Data from nonresponders was obtained from obstetric records. Of the total sample, 30% smoked during their last pregnancy. There were significant differences between responders and nonresponders. The responders contained only 60% of all smokers. Nonresponders had twice the incidence of smoking, were more likely to identify as Maori, were younger and had lower birth weights. Nonresponders contained 40% of all smokers. Of the responders, 333 mothers smoked during at least some part of pregnancy: 113 (34%) quit, 168 (50%) cut down, and 48 (15%) made no change. Most (90%) of those who did quit did so during the first trimester. Lighter smokers (less than 10 per day) were more likely to quit or cut down. But smoking rates subsequently increased after the birth. In Canterbury, 30% of pregnant women smoke. Although 64% indicated a wish to quit and 30% to cut down, this contrasted with what they actually achieved: 34% quit and 50% cut down. Pregnancy influences smoking patterns and is an opportune time for smokefree promotion.


Association of hyperplastic polyposis syndrome, colorectal cancer and meningioma.
Recent research has provided compelling evidence that a subset of hyperplastic polyps may be associated with a risk of colorectal cancer. Colorectal cancer with extracolonic manifestation is usually seen in a hereditary syndrome setting, but some association with meningioma has been reported. The association of colorectal cancer with hyperplastic polyposis and meningioma is extremely rare. This report in a 57-year-old female with no family history of colon cancer or polyps, could be the first case of hyperplastic polyposis syndrome, colorectal cancer and meningioma. Hyperplastic polyposis syndrome was diagnosed as per WHO criteria at the time of colon cancer diagnosis. Within 4 months of colon cancer diagnosis she developed seizures. Imaging of the brain revealed meningioma of the left cerebellopontine angle. The patient underwent surgery followed by chemotherapy.


Three Complementary Approaches to Characterize Buprenorphine Misuse.
In France, buprenorphine has been available for opioid maintenance therapy since 1996 and since then its misuse has been continuously evaluated by the French health authorities. To characterize buprenorphine misuse in Languedoc-Roussillon (LR) region, using three different approaches. Three different data sources were analyzed : (i) spontaneous reports (NotS) of buprenorphine misuse or dependence, (ii) a specific periodic survey from specialized care centers (OPPIDUM) over 11 years (2002-2012) and (iii) a drug reimbursement database (DRB). A total of 209 spontaneous reports were collected. The main type of buprenorphine misuse was use by an unintended route of administration. The main complications notified were directly related to the injection of buprenorphine. NotS enabled the collection of data about severe clinical complications or new diversion phenomenon. The OPPIDUM LR survey revealed a decrease in the buprenorphine misuse indicator through the study period. The DRB analysis identified one subgroup of patients with a buprenorphine deviant behavior, characterized by a significantly greater number of dispensing episodes, pharmacies, prescribers, daily dose and switch between buprenorphine forms (princeps and generic). The DRB analysis provides data on buprenorphine diversion in the context of outpatients care. The three complementary approaches allowed us to characterize buprenorphine misuse in LR area. The three approaches are complementary because each data source provides different types of information.


[Ascites due to portal hypertension from breast cancer- related metastatic liver infiltration].
Ascites in patients with breast cancer is uncommon. We report the case of a 70-year-old woman with breast cancer and ascites caused by portal hypertension due to metastatic liver infiltration. There was no evidence of peritoneal carcinomatosis and the prothrombin index was normal. Portal hypertension was confirmed by increased hepatic venous pressure gradient. Histological examination of a liver biopsy obtained by the transjugular route demonstrated infiltration by malignant cells from the breast tumor. This case shows that, infiltration of the liver by metastases from breast cancer may lead to ascites due to portal hypertension, even in the absence of hepatic failure.


Pulsed dye laser for the treatment of nail psoriasis.
Psoriasis can involve the skin, joints, and nails, either alone or in combination. Psoriasis of the nails can involve both the nail bed and nail matrix. The treatment of nail psoriasis largely depends on the severity of symptoms. The pulsed dye laser (PDL) recently has demonstrated efficacy in treating resistant plaque-type psoriasis and has been suggested as an alternative to conventional therapies. We review 4 studies of PDL for nail psoriasis and discuss the findings in relation to treatment recommendations. Ultimately, a standardized regimen for the treatment of nail psoriasis remains elusive.


[Clinical study on painless labor under drugs combined with acupuncture analgesia].
To study the analgesia efficacy of drugs combined with acupuncture analgesia for painless labor, 462 normal pregnancy women were observed. During the latent phase in labor, several analgesia methods: acupuncture analgesia, analgesics, magnetotherapy and auricular acupressure, TENS combined with dihydroetorphine were used respectively. While the intrauterine pressure and the peripheral content of beta-EP were measured during labor, the experiments of SEPS were also performed on healthy adults to demonstrate the analgesia efficacy of those analgesia methods. The combination of drugs with acupuncture is an excellent method for painless labor without any complications and all the mothers and babies are safety. The effectiveness is 97.5%. The results demonstrate that the mechanism of analgesia efficacy should be regulated the incoordinate uterine action and improve the hypertonic status of uterus, but also can decrease the pain threshold and elevate the tolerance of uterine contractions during labor.


Charting a path for health sciences librarians in an integrated information environment.
Changes in the health information environment present a major challenge to health sciences librarians. To successfully meet this challenge, librarians must apply the concepts of informal, self-directed, lifelong learning to their own carers. The Joint Commission on Accreditation of Healthcare Organizations is creating an integrated information environment in health care organizations. The health sciences librarian brings unique knowledge and skills to this environment. The reference technique, a methodology that closely parallels other problem-solving approaches such as the physician's diagnostic technique, equips librarians with the conceptual skills to develop creative solutions to information management problems. Each health sciences librarian must assume responsibility for extending professional skills and abilities and demonstrating them in the workplace.


Association between Dietary Nitrate, Nitrite Intake, and Site-Specific Cancer Risk: A Systematic Review and Meta-Analysis.
People consume nitrates, nitrites, nitrosamines, and NOCs compounds primarily through processed food. Many studies have yielded inconclusive results regarding the association between cancer and dietary intakes of nitrates and nitrites. This study aimed to quantify these associations across the reported literature thus far. We performed a systematic review following PRISMA and MOOSE guidelines. A literature search was performed using Web of Science, Embase, PubMed, the Cochrane library, and google scholar up to January 2020. STATA version 12.0 was used to conduct meta-regression and a two-stage meta-analysis. A total of 41 articles with 13 different cancer sites were used for analysis. Of these 13 cancer types/sites, meta-regression analysis showed that bladder and stomach cancer risk was greater, and that pancreatic cancer risk was lower with increasing nitrite intakes. Kidney and bladder cancer risk were both lower with increasing nitrate intakes. When comparing highest to lowest (reference) categories of intake, meta-analysis of studies showed that high nitrate intake was associated with an increased risk of thyroid cancer (OR = 1.40, 95% CI: 1.02, 1.77). When pooling all intake categories and comparing against the lowest (reference) category, higher nitrite intake was associated with an increased risk of glioma (OR = 1.12, 95% CI: 1.03, 1.22). No other associations between cancer risk and dietary intakes of nitrates or nitrites were observed. This study showed varied associations between site-specific cancer risks and dietary intakes of nitrate and nitrite. Glioma, bladder, and stomach cancer risks were higher and pancreatic cancer risk was lower with higher nitrite intakes, and thyroid cancer risk was higher and kidney cancer risk lower with higher nitrate intakes. These data suggest type- and site-specific effects of cancer risk, including protective effects, from dietary intakes of nitrate and nitrite.