Impact of interventions on malaria in internally displaced persons along the China-Myanmar border: 2011-2014.
Internally displaced persons (IDP) represent vulnerable populations whose public health conditions merit special attention. In the China-Myanmar border area, human movement and resettlements of IDP can influence malaria transmission. Comparison of disease incidence and vector densities between IDP camps and surrounding local villages allows for better understanding of current epidemiology and to evaluate the effectiveness of interventions in the region. Malaria and vector surveillance was conducted in three IDP camps and three local villages neighbouring the camps along the China-Myanmar border in Myanmar. Clinical malaria cases were collected from seven hospitals/clinics from April 2011 to December 2014. Malaria vector population dynamics were monitored using CDC light traps. The use of malaria preventive measures and information on aid agencies and their activities was obtained through questionnaire surveys. Malaria was confirmed in 1832 patients. Of these cases, 85.4 % were Plasmodium vivax and 11.4 % were Plasmodium falciparum malaria. Annual malaria incidence rates were 38.8 and 127.0 cases/1000 person year in IDP camps and local villages, respectively. Older children of 5-14 years had the highest incidence rate in the camps regardless of gender, while male adults had significantly higher incidence rates than females in local villages and females child-bearing age had significantly lower risk to malaria in IDP camps compare to local villages. Seasonal malaria outbreaks were observed both in the IDP camps and in the local villages from May to August 2013. The proportion of P. vivax remained unchanged in local villages but increased by approximately tenfold in IDP camps from 2011 to 2014. Anopheles vector density was tenfold higher in local villages compared to IDP camps (2.0:0.2 females/trap/night). Over 99 % of households in both communities owned bed nets. While long-lasting insecticidal nets accounted for 61 % of nets used in IDPs, nearly all residents of local villages owned regular nets without insecticide-impregnation. There were more active aid agencies in the camps than in local villages. Malaria in IDP camps was significantly lower than the surrounding villages through effective control management. The observation of P. vivax outbreaks in the study area highlights the need for increased control efforts. Expansion of malaria intervention strategies in IDP camps to local surrounding villages is critical to malaria control in the border area.


Biochemical characterization of the tetrahydrobiopterin synthesis pathway in the oleaginous fungus Mortierella alpina.
We characterized the de novo biosynthetic pathway of tetrahydrobiopterin (BH₄) in the lipid-producing fungus Mortierella alpina. The BH₄ cofactor is essential for various cell processes, and is probably present in every cell or tissue of higher organisms. Genes encoding two copies of GTP cyclohydrolase I (GTPCH-1 and GTPCH-2) for the conversion of GTP to dihydroneopterin triphosphate (H₂-NTP), 6-pyruvoyltetrahydropterin synthase (PTPS) for the conversion of H₂-NTP to 6-pyruvoyltetrahydropterin (PPH₄), and sepiapterin reductase (SR) for the conversion of PPH₄ to BH₄, were expressed heterologously in Escherichia coli. The recombinant enzymes were produced as His-tagged fusion proteins and were purified to homogeneity to investigate their enzymic activities. Enzyme products were analysed by HPLC and electrospray ionization-MS. Kinetic parameters and other properties of GTPCH, PTPS and SR were investigated. Physiological roles of BH₄ in M. alpina are discussed, and comparative analyses between GTPCH, PTPS and SR proteins and other homologous proteins were performed. The presence of two functional GTPCH enzymes has, as far as we are aware, not been reported previously, reflecting the unique ability of this fungus to synthesize both BH₄ and folate, using the GTPCH product as a common substrate. To our knowledge, this study is the first to report the comprehensive characterization of a BH₄ biosynthesis pathway in a fungus.


Evaluation of carbon dioxide laser irradiation associated with calcium hydroxide in the treatment of dentinal hypersensitivity. A preliminary study.
Attempts have been made to treat dentinal hypersensitivity by sealing exposed dentinal tubules, and the carbon dioxide (CO(2)) laser has been shown to have a sealing effect on dentinal surfaces. The purpose of this study was to analyze the morphological ultra-structure and temperature change after CO(2) laser irradiation of dentin. Fourteen human third molars were selected and cleaned. An area was delimited, and the samples were randomly divided into seven groups: Group 1 (G1): control; G2, calcium hydroxide paste (CA) + CO(2) laser (L) (0.5 W/63,69 W/cm(2)); G3, CA + L (1 W/125,38 W/cm(2)); G4, CA + L (1.5 W/191,08 W/cm(2)); G5, L (0.5 W); G6, L (1 W); G7, L (1.5 W). All irradiation was performed in unfocused mode. The electron micrographs were analyzed by three observers. For temperature analysis, a thermocouple was used. Data were subjected to statistical analysis. The Kruskal-Wallis non-parametric test showed statistical differences between the groups (P < 0.05). For the two by two comparisons, all groups treated with calcium hydroxide paste presented significantly higher mean scores. In the groups treated by CO(2) laser only, fusion, re-crystallization, cracks and carbonization were observed. A change of 1 ± 5°C was noted in the temperature. Under the limitation of an in vitro study, and with the protocols used, we concluded that CO(2) laser is safe to use for the establishment of partial fusion and re-solidification of the dentinal surface.


High altitude and blood pressure in children.
We aimed to evaluate the blood pressure of children who had similar demographic characteristics but lived at different altitudes. Blood pressure of the children attending primary schools in Izmir (sea level: n = 425) and Van (altitude: 1725 m, n = 291) were measured by mercurial sphygmomanometer for this study. They were similar with respect to age, sex, weight, height, and BMI. Mean age of the children was 10.51 +/- 0.87 years (range: 9 to 12 years), and 358 (50 percent) of them were female. Mean systolic blood pressure was significantly higher in the children living in Van than in the children living in Izmir (104.72 +/- 11.2 vs. 97.96 +/- 25.5 mmHg, respectively, p < .001). Similarly mean diastolic blood pressure was significantly higher in the children living in Van than in the children living in Izmir (63.98 +/- 9.3 vs. 59.91 +/- 10.0 mmHg, respectively, p < .001). When blood pressure was evaluated with regard to height percentile, the number of children with a blood pressure over 90 percentile were 19 (4.5 percent) and 48 (16.5 percent) for systolic blood pressure, and 25 (5.9 percent) and 37 (12.7 percent) for diastolic blood pressure among the children living in Izmir and Van, respectively (p < .001). Systolic and diastolic blood pressures were found to increase in parallel to the increase in body mass index in children living in Van (r = 0.358, p < .001 and r = 0.235, p < .001, respectively). However, blood pressures were not correlated to body mass index in children living in Izmir. A difference of 1700 m in altitude was associated with higher systolic and diastolic blood pressure levels in children with similar demographic characteristics, and at this altitude, body mass index and blood pressure showed a positive correlation.


Peripheral blood-derived mesenchymal stem cells: candidate cells responsible for healing critical-sized calvarial bone defects.
Postnatal tissue-specific stem/progenitor cells hold great promise to enhance repair of damaged tissues. Many of these cells are retrieved from bone marrow or adipose tissue via invasive procedures. Peripheral blood is an ideal alternative source for the stem/progenitor cells because of its ease of retrieval. We present a coculture system that routinely produces a group of cells from adult peripheral blood. Treatment with these cells enhanced healing of critical-size bone defects in the mouse calvarium, a proof of principle that peripheral blood-derived cells can be used to heal bone defects. From these cells, we isolated a subset of CD45(-) cells with a fibroblastic morphology. The CD45(-) cells were responsible for most of the differentiation-induced calcification activity and were most likely responsible for the enhanced healing process. These CD45(-) fibroblastic cells are plastic-adherent and exhibit a surface marker profile negative for CD34, CD19, CD11b, lineage, and c-kit and positive for stem cell antigen 1, CD73, CD44, CD90.1, CD29, CD105, CD106, and CD140α. Furthermore, these cells exhibited osteogenesis, chondrogenesis, and adipogenesis capabilities. The CD45(-) fibroblastic cells are the first peripheral blood-derived cells that fulfill the criteria of mesenchymal stem cells as defined by the International Society for Cellular Therapy. We have named these cells "blood-derived mesenchymal stem cells."


Expression, purification and characterization of a human serine-dependent phospholipase A2 with high specificity for oxidized phospholipids and platelet activating factor.
Using expressed sequence tag (EST) homology screening, a new human serine dependent phospholipase A2 (HSD-PLA2) was identified that has 40% amino acid identity with human low density lipoprotein-associated phospholipase A2 (LDL-PLA2). HSD-PLA2 has very recently been purified and cloned from brain tissue but named PAF-AH II. However, because the homology with LDL-PLA2 suggested a broader substrate specificity than simply platelet activating factor (PAF), we have further characterized this enzyme using baculovirus-expressed protein. The recombinant enzyme, which was purified 21-fold to homogeneity, had a molecular mass of 44kDa and possessed a specific activity of 35 micromol min-1 mg-1 when assayed against PAF. Activity could also be measured using 1-decanoyl-2-(4-nitrophenylglutaryl) phosphate (DNGP) as substrate. Like LDL-PLA2, HSD-PLA2 was able to hydrolyse oxidatively modified phosphatidylcholines when supplemented to human LDL prior to copper-stimulated oxidation. A GXSXG motif evident from sequence information and inhibition of its activity by 3,4, dichloroisocoumarin, diisopropyl fluorophosphate (DFP) and diethyl p-nitrophenyl phosphate (DENP) confirm that the enzyme is serine dependent. Moreover, sequence comparison indicates the HSD-PLA2 probable active site triad positions are shared with LDL-PLA2 and a C. elegans homologue, suggesting that these sequences comprise members of a new enzyme family. Although clearly structurally related with similar substrate specificities further work reported here shows HSD-PLA2 and LDL-PLA2 to be different with respect to chromosomal localization and tissue distribution.


Mammalian ets-1 and ets-2 genes encode highly conserved proteins.
Cellular ets sequences homologous to v-ets of the avian leukemia virus E26 are highly conserved. In mammals the ets sequences are dispersed on two separate chromosomal loci, called ets-1 and ets-2. To determine the structure of these two genes and identify the open reading frames that code for the putative proteins, we have sequenced human ets-1 cDNAs and ets-2 cDNA clones obtained from both human and mouse. The human ETS1 gene is capable of encoding a protein of 441 amino acids. This protein is greater than 95% identical to the chicken c-ets-1 gene product. Thus, the human ETS1 gene is homologous to the chicken c-ets-1 gene, the protooncogene that the E26 virus transduced. Human and mouse ets-2 cDNA clones are closely related and contain open reading frames capable of encoding proteins of 469 and 468 residues, respectively. Direct comparison of these data with previously published findings indicates that ets is a family of genes whose members share distinct domains.


Mild traumatic brain injury in U.S. Soldiers returning from Iraq.
An important medical concern of the Iraq war is the potential long-term effect of mild traumatic brain injury, or concussion, particularly from blast explosions. However, the epidemiology of combat-related mild traumatic brain injury is poorly understood. We surveyed 2525 U.S. Army infantry soldiers 3 to 4 months after their return from a year-long deployment to Iraq. Validated clinical instruments were used to compare soldiers reporting mild traumatic brain injury, defined as an injury with loss of consciousness or altered mental status (e.g., dazed or confused), with soldiers who reported other injuries. Of 2525 soldiers, 124 (4.9%) reported injuries with loss of consciousness, 260 (10.3%) reported injuries with altered mental status, and 435 (17.2%) reported other injuries during deployment. Of those reporting loss of consciousness, 43.9% met criteria for post-traumatic stress disorder (PTSD), as compared with 27.3% of those reporting altered mental status, 16.2% with other injuries, and 9.1% with no injury. Soldiers with mild traumatic brain injury, primarily those who had loss of consciousness, were significantly more likely to report poor general health, missed workdays, medical visits, and a high number of somatic and postconcussive symptoms than were soldiers with other injuries. However, after adjustment for PTSD and depression, mild traumatic brain injury was no longer significantly associated with these physical health outcomes or symptoms, except for headache. Mild traumatic brain injury (i.e., concussion) occurring among soldiers deployed in Iraq is strongly associated with PTSD and physical health problems 3 to 4 months after the soldiers return home. PTSD and depression are important mediators of the relationship between mild traumatic brain injury and physical health problems.


Effects of stellate ganglion block on perimenopausal hot flashes: a randomized controlled trial.
Hot flashes are common symptoms afflicting perimenopausal women. A stellate ganglion block (SGB) is believed to be an effective treatment for hot flashes; however, more evidence is needed to evaluate its safety and efficacy in relieving perimenopausal hot flashes. To investigate the efficacy and safety of SGB for the treatment of perimenopausal hot flashes. A randomized controlled trial was conducted at Shanxi Bethune Hospital. Forty perimenopausal women with hot flashes were recruited from April 2022 to November 2022 and randomly assigned to receive either 6 consecutive SGB treatments or 6 consecutive saline placebo treatments. The primary outcome was the change in hot flash symptom score from baseline to 12 weeks after treatment. The secondary outcomes were the change in hot flash symptom score from baseline to 12 weeks after treatment and the post-treatment Kupperman Index (KI) and Pittsburgh Sleep Quality Index (PSQI) scores. Of the 40 randomized subjects, 35 completed the study. All the variables were significantly improved. During 12 weeks of follow-up, the hot flash scores, Kupperman Menopause Scale scores, and Pittsburgh Sleep Quality Scale scores decreased significantly. Two subjects in the SGB treatment group experienced transient hoarseness, and the incidence of related adverse events was 10%. No related adverse events occurred in the control group. Compared to the control treatment, SGB treatment was a safe and effective nonhormone replacement therapy that significantly relieved perimenopausal hot flashes and effectively improved sleep quality. Additional studies are needed to assess the long-term efficacy of this therapy.


The levels of peroxisomal catalase protein and activity modulate the onset of cell death in tobacco BY-2 cells via reactive oxygen species levels and autophagy.
In plant cells, peroxisomes participate in the metabolism of reactive oxygen species (ROS). One of the major regulators of cellular ROS levels - catalase (CAT) - occurs exclusively in peroxisomes. CAT activity is required for immunity-triggered autophagic programmed cell death (PCD). Autophagy has been recently demonstrated to represent a route for degradation of peroxisomes in plant cells. In the present study, the dynamics of the cellular peroxisome pool in tobacco BY-2 cell suspension cultures were used to analyse the effects of inhibition of basal autophagy with special attention to CAT activity. Numbers of peroxisomes per cell, levels of CAT protein and activity, cell viability, ROS levels and expression levels of genes encoding components of antioxidant system were analysed upon application of 3-methyladenine (3-MA), an inhibitor of autophagy, and/or aminotriazole (AT), an inhibitor of CAT. When applied separately, 3-MA and AT led to an increase in cell death, but this effect was attenuated by their simultaneous application. The obtained data suggest that both the levels of CAT protein in peroxisomes as well as CAT activity modulate the onset of cell death in tobacco BY-2 cells via ROS levels and autophagy.


Structural and Functional Survey of Environmental Aminoglycoside Acetyltransferases Reveals Functionality of Resistance Enzymes.
Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al. Nature 2014 , 509 , 612 ). These enzymes are new members of the Gcn5-Related-N-Acetyltransferase superfamily and confer resistance to the aminoglycosides gentamicin C, sisomicin, and tobramycin. Moreover, the meta-AAC0020 enzyme demonstrated activity comparable with an AAC(3)-I enzyme that serves as a model AAC enzyme identified in a clinical bacterial isolate. The crystal structure of meta-AAC0020 in complex with sisomicin confirmed an unexpected AAC(6') regiospecificity of this enzyme and revealed a drug binding mechanism distinct from previously characterized AAC(6') enzymes. Together, our data highlights the presence of highly active antibiotic-modifying enzymes in the environmental microbiome and reveals unexpected diversity in substrate specificity. These observations of additional AAC enzymes must be considered in the search for novel aminoglycosides less prone to resistance.


From molecular control to quantum technology with the dynamic Stark effect.
The non-resonant dynamic Stark effect is a powerful and general way of manipulating ultrafast processes in atoms, molecules, and solids with exquisite precision. We discuss the physics behind this effect, and demonstrate its efficacy as a method of control in a variety of systems. These applications range from the control of molecular rotational dynamics to the manipulation of chemical reaction dynamics, and from the suppression of vacuum fluctuation effects in coherent preparation of matter, to the dynamic generation of bandwidth for storage of broadband quantum states of light.


Negative pressure driven phase transformation in Sr doped SmCoO₃.
Atomistic computer simulation techniques based on energy minimization procedures are utilized for the structural investigation of perovskite-type SmCoO(3). A reliable potential model is derived which reproduces both cubic as well as orthorhombic phases of SmCoO(3). We observe a negative chemical pressure induced structural phase transformation from distorted perovskite (orthorhombic) to perfect perovskite (cubic) due to the substitution of Sr(2 + ) at the Sm(3 + ) sites. However, external hydrostatic pressure shows isotropic compression and no pressure-induced structural transformation is observed up to 100 GPa. To maintain the electroneutrality of the system, charge compensation is through oxygen vacancies which results in the brownmillerite-type structure. A defect model is proposed, which is consistent with experimental results. The solution energies for divalent and trivalent cations are also calculated. These results show that the cations having ionic radii less than 0.75 Å will occupy the Co sites and those with ionic radii larger than 0.75 Å will substitute at the Sm sites.


Mutagenicity of nitrite-treated soy sauce in Chinese hamster V79 cells.
Mutagenicity of 4 kinds of Japanese soy sauce and tyramine, which is a precursor of a mutagen (3-diazotyramine) and present in soy sauce, after nitrite treatment under a yellow lamp was studied in Chinese hamster V79 cells with 6-thioguanine (TG) as a selective marker. The frequencies of mutation caused by nitrite-treated samples of soy sauce increased in the V79 cells in a dose-dependent manner. Four kinds of nitrite-treated soy sauce induced 139 to 473 TG-resistant mutants per 10(5) clonable cells per milliliter of soy sauce equivalent in the cells. Nitrite-treated tyramine was also mutagenic for the cells; it induced 8.6, 13.3, and 18.3 TG-resistant mutants per 10(5) clonable cells at concentrations of 20 micrograms, 56 micrograms, and 112 micrograms, respectively.


A scoping review of studies comparing the medication event monitoring system (MEMS) with alternative methods for measuring medication adherence.
Different methods are available for measuring medication adherence. In this paper, we conducted a scoping review to identify and summarize evidence of all studies comparing the Medication Event Monitoring System (MEMS) with alternative methods for measuring medication adherence. A literature search was performed using the open database www.iAdherence.org that includes all original studies reporting findings from the MEMS. Papers comparing methods for measuring adherence to solid oral formulations were included. Data was extracted using a standardized extraction table. A total of 117 articles fulfilled the inclusion criteria, including 251 comparisons. Most frequent comparisons were against self-report (n = 119) and pill count (n = 59). Similar outcome measures were used in 210 comparisons (84%), among which 78 used dichotomous variables (adherent or not) and 132 used continuous measures (adherence expressed as percentage). Furthermore, 32% of all comparisons did not estimate adherence over the same coverage period and 44% of all comparisons did not use a statistical method or used a suboptimal one. Only eighty-seven (35%) comparisons had similar coverage periods, similar outcome measures and optimal statistical methods. Compared to MEMS, median adherence was grossly overestimated by 17% using self-report, by 8% using pill count and by 6% using rating. In conclusion, among all comparisons of MEMS versus alternative methods for measuring adherence, only a few used adequate comparisons in terms of outcome measures, coverage periods and statistical method. Researchers should therefore use stronger methodological frameworks when comparing measurement methods and be aware that non-electronic measures could lead to overestimation of medication adherence.


CaMKII "autonomy" is required for initiating but not for maintaining neuronal long-term information storage.
Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) "autonomy" (T286-autophosphorylation-induced Ca(2+)-independent activity) is required for long-term potentiation (LTP) and for learning and memory, as demonstrated by CaMKII T286A mutant mice. The >20-year-old hypothesis that CaMKII stimulation is required for LTP induction, while CaMKII autonomy is required for LTP maintenance was recently supported using the cell-penetrating fusion-peptide inhibitor antCN27. However, we demonstrate here that ant/penetratin fusion to CN27 compromised CaMKII-selectivity, by enhancing a previously unnoticed direct binding of CaM to ant/penetratin. In contrast to antCN27, the improved cell-penetrating inhibitor tatCN21 (5 mum) showed neither CaM binding nor inhibition of basal synaptic transmission. In vitro, tatCN21 inhibited stimulated and autonomous CaMKII activity with equal potency. In rat hippocampal slices, tatCN21 inhibited LTP induction, but not LTP maintenance. Correspondingly, tatCN21 also inhibited learning, but not memory storage or retrieval in a mouse in vivo model. Thus, CaMKII autonomy provides a short-term molecular memory that is important in the signal computation leading to memory formation, but is not required as long-term memory store.


Conversion of working memory to motor sequence in the monkey premotor cortex.
To plan a serial order behavior, we hold serial sensory information in our minds and convert it to a movement program. We trained monkeys to memorize a sequence of positional cues and to reproduce it by making saccades in either the original or reverse order. The order was determined in the middle of a trial on the basis of an instruction stimulus. Triggered by the instruction stimulus, single neurons in the dorsal premotor cortex became transiently active only when the order needed to be determined. These transient neurons, together with nearby sustained neurons that hold information on cue or movement sequences, appear to mediate the generation of a motor program from the maintained information.


Tumor necrosis factor blocking therapy and congestive heart failure in patients with inflammatory rheumatic disorders: a systematic review.
Tumour necrosis factor (TNF) blocking therapy is an effective treatment for chronic inflammatory arthritis. As circulating TNF might induce or exacerbate the development of congestive heart failure (CHF), several trials have investigated the effect of TNF blocking therapy on CHF. However, due to inefficacy and even a risk of exacerbation of CHF, TNF blocking therapy has since then been contraindicated in patients with advanced CHF, New York Heart Association class III and IV. We review current knowledge on the pathophysiological mechanisms and safety of TNF blocking therapy in chronic inflammatory arthritis patients with regard to CHF. A systematic search of the literature published up till December 2013 was conducted in MEDLINE, EMBASE and the Cochrane Library to identify all studies investigating the effect of TNF blocking therapy on the occurrence and risk of CHF in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). All articles reporting data on the prevalence or incidence of CHF during treatment with TNF blocking therapy in patients with in RA, AS or PsA were included. Also imaging studies and studies with biomarkers, investigating the effect of TNF blocking therapy on cardiac function were included. In total, 54 studies were included. Results from large prospective registries suggest that first, a potentially harmful effect of TNF blocking therapy on the incidence of CHF in older RA patients cannot be excluded and that no harmful effect was observed of TNF blocking therapy in other patients. Second, we found that TNF blocking therapy potentially improves several echocardiographic parameters of cardiac function in RA, AS and PsA, but due to small sample sizes, these results require validation in larger studies. Third, we found improvement in NT-proBNP levels after use of TNF blocking therapy in both RA and AS. Based on current literature, in patients with chronic inflammatory arthritis and concomitant symptomatic mild-tomoderate CHF (NYHA class I or II), treatment with TNF blocking therapy is not contraindicated. In chronic inflammatory arthritis patients with concomitant symptomatic moderate-to-severe CHF, NYHA class III-IV, treatment with TNF blocking therapy should be avoided if possible. Whenever, treatment with TNF-blocking therapy is considered in these patients consultation with a cardiologist is recommended before treatment is initiated.


Portable infrared imaging for longitudinal limb volume monitoring in patients with lymphatic filariasis.
The Global Programme to Eliminate Lymphatic Filariasis (LF) emphasizes hygiene, exercise, and other measures to reduce morbidity and disability related to LF. We recently reported that a portable, three-dimensional, infrared imaging system (3DIS) provides accurate limb volume measurements in patients with filarial lymphedema. To assess the practical utility of repeated 3DIS measurements for longitudinal lymphedema management, we examined intraday and day-to-day leg volume changes in adults with filarial lymphedema in southern Sri Lanka. We assessed 41 participants with lower extremity lymphedema (stages 1-6) in their homes in the mornings (6:00-9:00 AM) and afternoons (2:00-6:00 PM) of three days within one calendar week. Two examiners performed replicate 3DIS volume measurements at each visit. Median coefficient of variation among replicate volume measurements was 1.7% (IQR 1.1% - 2.3%) for left legs and 2.2% (IQR 1.6% - 2.8%) for right legs. Median intraday volume increase was 3.0%. Range among daily volume measurements tended to be lower for afternoon measurements (median 2.25%, IQR 1.4%- 5.4%) than for morning measurements (median 3.0%, IQR 1.4% - 8.4%). Limb volume measurements by 3DIS are accurate and reproducible, and this technique is feasible for use in patients' homes. We have developed practical suggestions for optimal outcomes with 3DIS. Duplicate measurements should be performed and repeat assessments should be done at approximately the same time of day to minimize bias. Duplicate measures that vary by more than 8% should prompt review of scanning technique with a repeat measurement. With proper training and attention to technique, 3DIS can be a valuable tool for healthcare workers who work with lymphedema patients.


Towards Evidence-Based Guidelines in Neurological Surgery.
Neurological surgery practice is based on the science of balancing probabilities. A variety of clinical guidance documents have influenced how we collectively practice our art since the early 20th century. The quality of the science within these guidelines varies widely, as does their utility in positively shaping our practice. The guidelines development process in neurological surgery has evolved significantly over the last 30 yr. Historically based in expert opinion, as a specialty we have increasingly relied on objective medical evidence to guide our clinical practice. We assessed the changing practice guidelines development process and the impact of scientifically robust guidelines on patient care. The evolution of the guidelines development process in neurological surgery was chronicled. Several subspecialty guidelines were extracted and reviewed in detail. Their impact on practice patterns was evaluated. The importance of evidence-based research and practice guidelines development was discussed. Evidence-based practice guidelines serve to chronicle multiple acceptable treatment options and help us move towards more standardized care for specific disease processes. They help refute false "standards of care." Guidelines-based care supported by solid medical evidence has the potential to streamline patient care and improve patient outcomes. The guidelines development process identifies areas, issues, and strategies for which little medical evidence exists, as well as topics that need focused scientific investigation and future study. The production of evidence-based practice recommendations is a vital part of furthering our specialty. Guidelines development advances our science, augments the resident education process, and protects our practice from undue external influence.


Complex spike synchrony dependent modulation of rat deep cerebellar nuclear activity.
The rules governing cerebellar output are not fully understood, but must involve Purkinje cell (PC) activity, as PCs are the major input to deep cerebellar nuclear (DCN) cells (which form the majority of cerebellar output). Here, the influence of PC complex spikes (CSs) was investigated by simultaneously recording DCN activity with CSs from PC arrays in anesthetized rats. Crosscorrelograms were used to identify PCs that were presynaptic to recorded DCN cells (presynaptic PCs). Such PCs were located within rostrocaudal cortical strips and displayed synchronous CS activity. CS-associated modulation of DCN activity included a short-latency post-CS inhibition and long-latency excitations before and after the CS. The amplitudes of the post-CS responses correlated with the level of synchronization among presynaptic PCs. A temporal precision of ≤10 ms was generally required for CSs to be maximally effective. The results suggest that CS synchrony is a key control parameter of cerebellar output. This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).


[Studies on the lowering blood sugar substances from agrimony].
To isolate and identify the chemical constituents from the active section lowering blood sugar of agrimony. The compounds were separated by repeated silica gel, Sephadex LH-20 and HPLC chromatographies. The structures of compounds isolated were identified by analysis of their spectral data and chemical properties. Nine compounds were isolated from the active section with lowering blood sugar of agrimony and their structures were identified as apigenin-7-O-3-D-glucopyranoside (1), catechin (2), quercetin (3), rutin (4), kaempferol-3-O-alpha-L-rhamnoside (5), Kampferol-3-O-beta-D-glucopyranoside (6), lutcolin-7-O-beta-D-glucopyranosidc (7), 19alpha, 24-dihydroxy ursolic acid (8), 3,3'-di-O-mcthyl ellagic acid4-O-beta-D-glucopyranoside (9). Compounds 1, 7, 8, 9 are isolated from thia plant for the first time.


Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response.
Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler's murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration. More limited changes in Klk1, Klk7, and Klk10 were also observed. In addition, Klk1, Klk6, and Klk10 were dynamically regulated in T cells in vitro as a recall response to viral antigen and in activated monocytes, pointing to their activities in the development of adaptive and innate immune function. Together, these results point to overlapping and unique roles for multiple kallikreins in the development and progression of virus-mediated central nervous system inflammatory demyelinating disease, including activities in the development of the adaptive and innate immune response, in demyelination, and in progressive axon degeneration.


Acute hypertensive uveitis as the first presentation of multiple sclerosis.
Ophthalmic manifestations of multiple sclerosis are frequent including acute optic neuritis, ocular motor disturbances and intermediate uveitis. We report an unusual case of multiple sclerosis presenting as acute hypertensive uveitis. A 56-year-old man was referred by his family doctor with a 2-week history of right eye pain and decreased vision. Best-corrected visual acuity was Count Fingers on the right and 6/9-2 on the left. Intraocular pressure was 55mmHg and 14 mmHg on the right and left respectively. He had a right relative pupillary defect and a left internuclear ophthalmoplegia. Vitreous cells were present in the right eye and there was peripheral sclerosis and periphlebitis superior temporally. MRI Brain and Spine revealed multiple T2 hyperintense lesions consistent with multiple sclerosis. Multiple sclerosis may present initially with an acute elevation of intraocular pressure and intermediate uveitis.


Traditional herbs: mechanisms to combat cellular senescence.
Cellular senescence plays a very important role in the ageing of organisms and age-related diseases that increase with age, a process that involves physiological, structural, biochemical and molecular changes in cells. In recent years, it has been found that the active ingredients of herbs and their natural products can prevent and control cellular senescence by affecting telomerase activity, oxidative stress response, autophagy, mitochondrial disorders, DNA damage, inflammatory response, metabolism, intestinal flora, and other factors. In this paper, we review the research information on the prevention and control of cellular senescence in Chinese herbal medicine through computer searches of PubMed, Web of Science, Science Direct and CNKI databases.


Increased resting-state functional connectivity in suprasellar tumor patients with postoperative visual improvement.
Background and Objective: Large suprasellar tumors often compress the optic chiasm and give rise to visual impairment. Most patients have significantly improved visual function at 1 to 4 months after chiasmal decompression surgery, and only a few individuals regain normal vision at 1 week after surgery. How the recovery of visual function in these patients affects the visual cortex is not fully understood. In this study, we aimed to investigate alterations in brain functional connectivity (FC) in suprasellar tumor patients with visual improvement using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: This longitudinal study was conducted on 13 suprasellar tumor patients who had ophthalmological examinations and rs-fMRI at the following time points: within 1-week preoperation (Pre-op), 1-week postoperation (Post-1w) and 1-month postoperation (Post-1m). The visual impairment score (VIS), local functional correlation (LCOR) and FC values were subjected to one-way ANOVA. Pearson correlation coefficients between changes in the LCOR and clinical factors were calculated. Results: The VIS was significantly decreased at both Post-1w and Post-1m compared to that at Pre-op. Whole-brain analysis of LCOR values showed that the left V1 (primary occipital cortex) was increased significantly at Post-1m compared to that at Pre-op (p < 0.05, FDR corrected). ROI analysis exhibited a significant negative correlation between the LCOR and VIS changes at Post-1m compared to those at Pre-op (p < 0.05, r = - 0.60). FC analysis within the visual network showed that the FC strengths were significantly increased between the left V5 and the left V4, right V3a, left V3, left V2d, and right V5 at Post-1m compared to those at Pre-op (p < 0.05, FDR corrected). Additionally, the FC strengths were significantly increased between the left V5 and the left V1, right orbital-frontal gyrus and left posterior supramarginal gyrus at the whole-brain network level at Post-1m compared to those at Pre-op (p < 0.05, FDR corrected). Conclusions: Postoperative visual improvement can be reflected by the increased FC of the visual cortex at Post-1w and Post-1m, especially at Post-1m. The LCOR value of the left V1 was associated with improved visual outcomes and may be used to objectively assess early visual recovery after chiasmal decompression at Post-1m.


Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN).
Congenital cutis laxa, a rare syndrome with marked skin laxity and pulmonary and cardiovascular compromise, is due to defective elastic fiber formation. In several cases, skin fibroblast tropoelastin production is markedly reduced yet reversed in vitro by transforming growth factor-beta treatment. We previously showed that this reversal was due to elastin mRNA stabilization in one cell strain, and here this behavior was confirmed in skin fibroblasts from two generations of a second family. cDNA sequencing and heteroduplex analysis of elastin gene transcripts from three fibroblast strains in two kindreds now identify two frameshift mutations (2012DeltaG and 2039DeltaC) in elastin gene exon 30, thus leading to missense C termini. No other mutations were present in the ELN cDNA sequences of all three affected individuals. Transcripts from both alleles in each kindred were unstable and responsive to transforming growth factor-beta. Exons 22, 23, 26A, and 32 were always absent. Since exon 30 underwent alternative splicing in fibroblasts, we speculate that a differential splicing pattern could conceivably lead to phenotypic rescue. These two dominant-acting, apparently de novo mutations in the elastin gene appear to be responsible for qualitative and quantitative defects in elastin, resulting in the cutis laxa phenotype.


Cardiac electrophysiological adaptations in the equine athlete-Restitution analysis of electrocardiographic features.
Exercising horses uniquely accommodate 7-8-fold increases in heart rate (HR). The present experiments for the first time analysed the related adaptations in action potential (AP) restitution properties recorded by in vivo telemetric electrocardiography from Thoroughbred horses. The horses were subjected to a period of acceleration from walk to canter. The QRS durations, and QT and TQ intervals yielded AP conduction velocities, AP durations (APDs) and diastolic intervals respectively. From these, indices of active, λ = QT/(QRS duration), and resting, λ0 = TQ/(QRS duration), AP wavelengths were calculated. Critical values of QT and TQ intervals, and of λ and λ0 at which plots of these respective pairs of functions showed unity slope, were obtained. These were reduced by 38.9±2.7% and 86.2±1.8%, and 34.1±3.3% and 85.9±1.2%, relative to their resting values respectively. The changes in λ were attributable to falls in QT interval rather than QRS duration. These findings both suggested large differences between the corresponding critical (129.1±10.8 or 117.4±5.6 bpm respectively) and baseline HRs (32.9±2.1 (n = 7) bpm). These restitution analyses thus separately identified concordant parameters whose adaptations ensure the wide range of HRs over which electrophysiological activation takes place in an absence of heart block or arrhythmias in equine hearts. Since the horse is amenable to this in vivo electrophysiological analysis and displays a unique wide range of heart rates, it could be a novel cardiac electrophysiology animal model for the study of sudden cardiac death in human athletes.


microRNA-34a is tumor suppressive in brain tumors and glioma stem cells.
We recently found that microRNA-34a (miR-34a) is downregulated in human glioma tumors as compared to normal brain, and that miR-34a levels in mutant-p53 gliomas were lower than in wildtype-p53 tumors. We showed that miR-34a expression in glioma and medulloblastoma cells inhibits cell proliferation, G1/S cell cycle progression, cell survival, cell migration and cell invasion, but that miR-34a expression in human astrocytes does not affect cell survival and cell cycle. We uncovered the oncogenes c-Met, Notch-1 and Notch-2 as direct targets of miR-34a that are inhibited by miR-34a transfection. We found that c-Met levels in human glioma specimens inversely correlate with miR-34a levels. We showed that c-Met and Notch partially mediate the inhibitory effects of miR-34a on cell proliferation and cell death. We also found that mir-34a expression inhibits in vivo glioma xenograft growth. We concluded that miR-34a is a potential tumor suppressor in brain tumors that acts by targeting multiple oncogenes. In this extra view, we briefly review and discuss the implications of these findings and present new data on the effects of miR-34a in glioma stem cells. The new data show that miR-34a expression inhibits various malignancy endpoints in glioma stem cells. Importantly, they also show for the first time that miR-34a expression induces glioma stem cell differentiation. Altogether, the data suggest that miR-34a is a tumor suppressor and a potential potent therapeutic agent that acts by targeting multiple oncogenic pathways in brain tumors and by inducing the differentiation of cancer stem cells.


Electron microscope study of the effect of benzalkonium, chlorhexidine and polymyxin on Pseudomonas cepacia.
Electron micrographs of Pseudomonas cepacia cell grown in nutrient broth show an external membrane which is distinctly wavy, when compared with similar preparations of Pseudomonas aeruginosa, and which is not affected by growing in the presence of broth containing benzalkonium (10 microgram/ml), chlorhexidine (10 microgram/ml) or polymyxin (25 units/ml). Both benzalkonium (10 microgram/ml) and chlorhexidine (10 microgram/ml) damage the cytoplasmic membrane of P. cepacia cell grown in the presence of the chemicals. Contrasts are shown between the effect of polymyxin (chlorhexidine and benzalkonium) on the outer membrane of P. cepacia and P. aeruginosa.


Water-induced finger wrinkles do not affect touch acuity or dexterity in handling wet objects.
Human non-hairy (glabrous) skin of the fingers, palms and soles wrinkles after prolonged exposure to water. Wrinkling is a sympathetic nervous system-dependent process but little is known about the physiology and potential functions of water-induced skin wrinkling. Here we investigated the idea that wrinkling might improve handling of wet objects by measuring the performance of a large cohort of human subjects (n = 40) in a manual dexterity task. We also tested the idea that skin wrinkling has an impact on tactile acuity or vibrotactile sensation using two independent sensory tasks. We found that skin wrinkling did not improve dexterity in handling wet objects nor did it affect any aspect of touch sensitivity measured. Thus water-induced wrinkling appears to have no significant impact on tactile driven performance or dexterity in handling wet or dry objects.


Virtual reality exposure therapy.
It has been proposed that virtual reality (VR) exposure may be an alternative to standard in vivo exposure. Virtual reality integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer-generated virtual environment. Virtual reality exposure is potentially an efficient and cost-effective treatment of anxiety disorders. VR exposure therapy reduced the fear of heights in the first controlled study of virtual reality in treatment of a psychiatric disorder. A case study supported the efficacy of VR exposure therapy for the fear of flying. The potential for virtual reality exposure treatment for these and other disorders is explored, and therapeutic issues surrounding the delivery of VR exposure are discussed.


Study protocol for a double-blind randomised controlled trial investigating the impact of 12 weeks supplementation with a Fucus vesiculosus extract on cholesterol levels in adults with elevated fasting LDL cholesterol who are overweight or have obesity.
Hyperlipidaemia, hyperglycaemia and chronic inflammation are risk factors for chronic diseases cardiovascular disease and type 2 diabetes. Polyphenols are bioactive compounds found in marine algae with potential antihyperlipidaemic, antihyperglycaemic and anti-inflammatory effects. The modulation of these risk factors using bioactive polyphenols may represent a useful strategy for disease prevention and management; research in humans, however, remains limited. This trial aims to determine the impact of a polyphenol-rich brown seaweed extract on fasting hyperlipidaemia, hyperglycaemia and inflammation. Effects on mood and cognition will also be evaluated. Fifty-eight hypercholesterolaemic participants who are overweight or have obesity will be randomised to receive either a polyphenol-rich brown seaweed extract (2000 mg dose containing 600 mg polyphenols) or placebo (2000 mg rice flour) daily for 12 weeks. Fasting venous blood samples will be taken at baseline, week 6 and week 12 of the intervention to assess serum cholesterol (total, low-density lipoprotein and high-density lipoprotein) and triglyceride concentrations, plasma glucose and insulin concentrations and markers of inflammation. Mood and cognitive function will be evaluated as exploratory outcomes. Independent t-tests or equivalent will be used to determine differences between the two groups in changes from baseline to week 12. Analysis of variance will be used to assess differences between the groups across the three time points (baseline, week 6 and week 12). Ethics approval has been granted by the Monash University Human Research Ethics Committee (2017-8689-10379). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations, and a PhD thesis. These results are essential to inform the use of polyphenol-rich brown seaweeds as a functional food or nutritional supplement ingredients for health promotion and disease prevention and management in humans. ACTRN12617001039370; Pre-results.


Intestinal tumor in a dish.
Predicting the response of colorectal cancer (CRC) tumors to novel chemotherapeutic agents is significantly complicated by their underlying genetic and epigenetic diversity. Large-scale clinical trials involving thousands of patients are often necessary in order to accurately determine efficacy during drug development. Recent advances in genetic sequencing has allowed us to improve the prediction of drug response through genetic stratification of patients into smaller populations, yet the complexity of the cancer genome still often confounds accuracy of drug response prediction. Ultimately, we may need to replicate patient's own tumor in a dish in order to test drug responses so that the optimal treatment can be identified. We recently developed highly efficient and tractable organoid culture system for intestinal stem cells, in which single stem cells form 3D structures recapitulating original tissue architecture. This technology has also been applied to colorectal tumors and enables us to monitor the growth and response of the patient's own tumors. In this review, we provide an overview focusing on CRC organoid culture and its perspective for clinical applications.


A Study of Upper-Limb Motion using Kinematic Measures for Clinical Assessment of Cerebellar Ataxia.
Cerebellar Ataxia (CA) is a group of diseases affecting the cerebellum, which is responsible for movement coordination. It causes uncoordinated movements and can also impact balance, speech, and eye movements. There are no approved disease-modifying medications for CA, so clinical studies to assess potential treatments are crucial. These studies require robust, objective measurements of CA severity to reflect changes in the progression of the disease due to medication. In recent years, studies have used kinematic measures to evaluate CA severity, but the current method relies on subjective clinical observations and is insufficient for telehealth. There is a need for a non-intrusive system that can monitor people with CA regularly to better understand the disease and develop an automated assessment system. In this study, we analyzed kinematic measures of upper-limb movements during a ballistic tracking test, which primarily involves movements at the shoulder joint. We aimed to understand the challenges of identifying CA and evaluating its severity when measuring such movements. Statistical features of the kinematic signals were used to develop machine learning models for classification and regression. The Gradient Boosting Classifier model had a maximum accuracy of 74%, but the models had low specificity and performed poorly in regression, suggesting that kinematic measures from shoulder-dominated movements during ballistic tracking are not as viable for CA assessment as other measures.


Retinal asymmetry in multiple sclerosis.
The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229-0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67-0.76) and IEAD (0.71, 95% CI 0.67-0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59-0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58-0.68, P < 0.0001) and macular RNFL IEPD AUROC curve (0.59, 95% CI 0.54-0.63, P < 0.0001); IEAD AUROC curve (0.55, 95% CI 0.50-0.59, P < 0.0001). Screening sensitivity levels for the macular GCIPL complex IEPD (4% cut-off) were 51.7% and for the IEAD (4 μm cut-off) 43.5%. Specificity levels were 82.8% and 86.8%, respectively. The number of co-morbidities was important. There was a stepwise decrease of the AUROC curve from 0.72 in control subjects to 0.66 in more than nine co-morbidities or presence of neuromyelitis optica spectrum disease. In the multivariable analyses greater age, diabetes mellitus, other eye disease and a non-white ethnic background were relevant confounders. For most interactions, the effect sizes were large (partial ω2 > 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed.


Sudden death associated with myocardial contraction band necrosis in Boer goat kids.
Parenteral selenium (Se) and vitamin E (Vit E) were administered to all newborn kids at a Boer goat farm where there was previous high neonatal mortality assumed to be due to nutritional myopathy. All treated kids were affected by severe respiratory distress and died within 8 hours of Se/Vit E administration. Gross lesions included severe pulmonary edema, hydrothorax, and hydropericardium. The primary histopathologic finding was severe, acute, and monophasic myocardial contraction band necrosis. The diagnosis was accidental acute selenosis based on trace mineral analysis of the liver. This case highlights an important differential diagnosis in cases of acute myocardial contraction band necrosis and sudden death in goats and emphasizes the need for caution when administering parenteral Se/Vit E preparations.


Optical puff mediated laminar-turbulent polarization transition.
Various physical structures exhibit a fundamentally probabilistic nature over diverse scales in space and time, to the point that the demarcation line between quantum and classic laws gets blurred. Here, we characterize the probability of intermittency in the laminar-turbulence transition of a partially mode-locked fiber laser system, whose degree of coherence is deteriorated by multiple mode mixing. Two competing processes, namely the proliferation and the decay of an optical turbulent puff, determine a critical behavior for the onset of turbulence in such a nonlinear dissipative system. A new kind of polarization rogue waves is introduced at the point of transition to polarization turbulence. The probabilistic description of the puff-mediated laminar-turbulence polarization transition provides an additional degree of freedom for our understanding of the complex physics of lasers.


Influence of immobilized biomolecules on magnetic bead plug formation and retention in capillary electrophoresis.
Significant changes in the formation and retention of magnetic bead plugs in a capillary during electrophoresis were studied, and it was demonstrated that these effects were due to the type of biological molecule immobilized on the surface of these beads. Three biological molecules, an antibody, an oligonucleotide, and alkaline phosphatase (AP), were attached to otherwise identical streptavidin-coated magnetic beads through biotin-avidin binding in order to isolate differences in bead immobilization in a magnetic field resulting from the type of biological molecule immobilized on the bead surface. AP was also attached to the magnetic beads using epoxy groups on the bead surfaces (instead of avidin-biotin binding) to study the impact of immobilization chemistry. The formation and retention of magnetic bead plugs were studied quantitatively using light scattering detection of magnetic particles eluting from the bead plugs and qualitatively using microscopy. Both the types of biomolecule immobilized on the magnetic bead surface and the chemistry used to link the biomolecule to the magnetic bead impacted the formation and retention of the bead plugs.


Medical and Dental Students' Perceptions and Attitudes towards Interprofessional Clinical Education.
This article was migrated. The article was marked as recommended. Purpose: Interest and expansion of interprofessional education (IPE) has increased tremendously over the last decade due to need and regulatory requirements. Methods: Third-year medical students and third and fourth-year dental students participated in a combined IPE experience at a dental assessment clinic. All participating students completed the Readiness for Interprofessional Learning Scale (RIPLS) Questionnaire before the session, and medical students completed an evaluation after the session. Results: All students agreed that IPE is important and needed for the development of skills, and they see benefit to shared learning. The only RIPLS question in which students did not agree was "Clinical problem solving can only be learnt effectively with students/ professionals from own school/organization." The dental students agreed with this more than medical students (p=0.04). Age of medical and dental students was related with outcomes of RIPLS questions 2, 7, 14, and 16 (p=0.03, 0.02, 0.03, and 0.02, respectively). Older participants from both schools tended not to agree with statements related to importance of working together benefiting patients, improving working relationships, welcoming the opportunity to work on small group projects with other health/social care students, and whether shared learning/practice will help clarify the nature of patients' problems. Medical student evaluations of the dental IPE experience were very positive, and mild changes in the curriculum improved medical student perception of the experience from year 1 to 2. Conclusion: Guidelines and standardized curricula could help medical and dental school faculty create clinically appropriate and effective IPE interactions for learners of all ages.


Glycerol and other fermentation products of apiculate wine yeasts.
Ninety-six strains of apiculate wine yeasts were studied for their ability to produce glycerol, acetaldehyde, ethyl acetate, sulphur dioxide and hydrogen sulphide in synthetic medium. Hanseniaspora guilliermondii produced smaller quantities of glycerol, acetaldehyde and hydrogen sulphide than Kloeckera apiculata, whereas the production of ethyl acetate and sulphur dioxide was found to be similar. Strains characterized by different capacities and properties were found for both species. The existence of apiculate strains differing in secondary compound production is of technological interest, as these yeasts constitute potential flavour producers. Selected strains of apiculate yeasts might favour an enhanced flavour formation and yield desirable characteristics to the final product.


Seroepidemiology of Toxoplasma gondii infection in patients with vision and hearing impairments, cancer, HIV, or undergoing hemodialysis in Durango, Mexico.
Toxoplasma gondii infection may cause a variety of symptoms involving virtually all organs. Little is known of the epidemiology of T. gondii infection in different patient groups in Mexico. We sought to determine the prevalence of T. gondii infection and associated epidemiological characteristics in 472 patients in Durango, Mexico. Participants were tested for T. gondii IgG and IgM antibodies. In addition, sociodemographic, clinical, and behavioral characteristics from each participant were obtained. Seroprevalences of T. gondii IgG antibodies were found in 7 (8.2%) of 85 patients with hearing impairment, 5 (10.0%) of 50 patients with hemodialysis, 28 (12.0%) of 234 patients with visual impairment, and 7 (6.8%) of 103 at risk of immunosuppression. In total, 47 (10%) of 472 subjects had IgG T. gondii antibodies; 6 (1.3%) of them also had IgM anti- T. gondii antibodies. Patients born in Durango State had a significantly lower prevalence of T. gondii infection than patients born in other Mexican states (9.0% vs. 21.4%, respectively; P < 0.05). Multivariate analysis showed that T. gondii infection was significantly associated with consumption of undercooked meat (adjusted odds ratio [OR] = 2.95; 95% confidence interval [CI]: 1.18-7.35) or raw cow's milk (adjusted OR = 2.52; 95% CI: 1.28-4.96), presence of cats at home (adjusted OR = 2.01; 95% CI: 1.06-3.78), raising animals (adjusted OR = 2.44; 95% CI: 1.06-5.63), or eating away from home (adjusted OR = 2.70; 95% CI: 1.03-7.11). In the group of patients with visual impairment, those with reflex impairment had a significantly higher frequency of T. gondii infection than those with normal reflexes (19% vs. 9.4%, respectively: P = 0.04). Results of the present study are the first step in the design of prevention programs to avoid the sequelae of toxoplasmosis.


Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry.
Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.


Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy.
To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM). Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine phthalate metabolites and creatinine were measured at the US Centers for Disease Control and Prevention. Associations between tertiles of phthalate metabolites concentrations and blood glucose levels were estimated using linear regression. Compared to pregnant women in the lowest concentration tertile, women with the highest urinary concentrations (≥ 3 rd tertile) of mono-iso-butyl phthalate (tertile: ≥ 15.3 μg/l, β = -18.3, 95% CI: -35.4, -1.2) and monobenzyl phthalate (tertile: ≥ 30.3 μg/l, β = -17.3, 95% CI: -34.1, -0.4) had lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine and demographic covariates. Because maternal glucose levels increase during pregnancy to provide adequate nutrition for fetal growth and development, these findings may have implications for fetal health. However, given the limitations of our study, findings should be interpreted cautiously.


Stimulation of tumor growth in adult rats in vivo during an acute fast.
These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast.


Importance of Prospective Registries and Clinical Research Networks in the Evolution of Spinal Cord Injury Care.
Only 100 years ago, traumatic spinal cord injury (SCI) was commonly lethal. Today, most people who sustain SCI survive with continual efforts to improve their quality of life and neurological outcomes. SCI epidemiology is changing as preventative interventions reduce injuries in younger individuals, and there is an increased incidence of incomplete injuries in aging populations. Early treatment has become more intensive with decompressive surgery and proactive interventions to improve spinal cord perfusion. Accurate data, including specialized outcome measures, are crucial to understanding the impact of epidemiological and treatment trends. Dedicated SCI clinical research and data networks and registries have been established in the United States, Canada, Europe, and several other countries. We review four registry networks: the North American Clinical Trials Network (NACTN) SCI Registry, the National Spinal Cord Injury Model Systems (SCIMS) Database, the Rick Hansen SCI Registry (RHSCIR), and the European Multi-Center Study about Spinal Cord Injury (EMSCI). We compare the registries' focuses, data platforms, advanced analytics use, and impacts. We also describe how registries' data can be combined with electronic health records (EHRs) or shared using federated analysis to protect registrants' identities. These registries have identified changes in epidemiology, recovery patterns, complication incidence, and the impact of practice changes such as early decompression. They've also revealed latent disease-modifying factors, helped develop clinical trial stratification models, and served as matched control groups in clinical trials. Advancing SCI clinical science for personalized medicine requires advanced analytical techniques, including machine learning, counterfactual analysis, and the creation of digital twins. Registries and other data sources help drive innovation in SCI clinical science.


Intrinsic reduced susceptibility of serotype 6 Streptococcus pyogenes to fluoroquinolone antibiotics.
Fluoroquinolone resistance is common in Staphylococcus aureus, is increasing in Streptococcus pneumoniae, and is reported in Streptococcus pyogenes. We surveyed 384 clinical isolates of S. pyogenes, isolated during 2002-2003, for susceptibility to ciprofloxacin. We performed nucleotide sequencing of the parC and gyrA genes and determined the M/emm type for selected isolates. Additionally, we analyzed M/emm type 6 S. pyogenes isolated during 1918-2003 from diverse locations. Of the survey isolates, 10.9% had reduced zones of inhibition to ciprofloxacin in the disk-diffusion test and had elevated minimum inhibitory concentrations to other fluoroquinolones, compared with those of fully susceptible isolates. Of the resistant isolates, 90.5% were M/emm type 6, and all sequenced M/emm type 6 isolates contained a serine-to-alanine substitution at position 79 in parC. Strikingly, the same findings were also present in macrolide-resistant isolates from a recent outbreak of S. pyogenes infection in Pittsburgh and in the Lancefield reference strain of M type 6, which was isolated in 1918, decades before the development of fluoroquinolone antibiotics. M/emm type 6 S. pyogenes has intrinsic reduced susceptibility to fluoroquinolones, as a result of a polymorphism in parC. This finding was also demonstrated in erythromycin-resistant M/emm type 6 S. pyogenes, which raises concern for the emergence of multidrug-resistant S. pyogenes.


Cytokeratin 7 immunoreactivity in rectal adenocarcinomas.
Colonic mucosa typically expresses cytokeratin (CK) 20 but not CK7. This CK20+/CK7- profile has been used to distinguish colonic adenocarcinoma from others arising in the lung, breast, or genitourinary tract. CK7 expression in colorectal adenocarcinoma has been reported to be rare, and when present, a metastatic origin needs to be excluded. However, we have observed a higher frequency of CK7 positivity in rectal adenocarcinomas. Paraffin sections of 42 rectal tumors (7 adenomas and 35 adenocarcinomas), 11 colonic adenocarcinomas proximal to the rectum, and 18 nonneoplastic rectoanal mucosa were randomly selected and immunostained for CK7 and CK20 with a standard avidin-biotin complex method. Immunoreactivity was recorded semiquantitatively. Cytoplasmic CK7 immunoreactivity was noted in 29 of 42 (69%) rectal glandular neoplasms (3 of 7 adenomas [43%] and 26 of 35 adenocarcinomas [74%]) and 9 of 18 (50%) nonneoplastic anorectal mucosal samples. In contrast, only 3 of the 11 (27%) colonic adenocarcinomas proximal to rectum were CK7 positive. Because of the relatively higher frequency of CK7 expression in rectal epithelial neoplasms, when CK7 is applied to distinguish primary colorectal versus metastatic origin, its reactivity should be interpreted with caution and should not be used as the sole evidence for excluding a rectal primary, particularly in tumors involving the rectal or pelvic region.


Lipid profile and statin use in critical care setting: implications for kidney outcome.
To determine whether pre-hospital statin use is associated with lower renal replacement therapy requirement and/or death during intensive care unit stay. Prospective cohort analysis. We analyzed 670 patients consecutively admitted to the intensive care unit of an academic tertiary-care hospital. Patients with ages ranging from 18 to 80 years admitted to the intensive care unit within the last 48 hours were included in the study. Mean age was 66±16.1 years old, mean body mass index 26.6±4/9kg/m2 and mean abdominal circumference was of 97±22cm. The statin group comprised 18.2% of patients and had lower renal replacement therapy requirement and/or mortality (OR: 0.41; 95%CI: 0.18-0.93; p=0.03). The statin group also had lower risk of developing sepsis during intensive care unit stay (OR: 0.42; 95%CI: 0.22-0.77; p=0.006) and had a reduction in hospital length-of-stay (14.7±17.5 days versus 22.3±48 days; p=0.006). Statin therapy was associated with a protective role in critical care setting independently of confounding variables, such as gender, age, C-reactive protein, need of mechanical ventilation, use of pressor agents and presence of diabetes and/or coronary disease. Statin therapy prior to hospital admission was associated with lower mortality, lower renal replacement therapy requirement and sepsis rates.


Insights into Roseburia intestinalis which alleviates experimental colitis pathology by inducing anti-inflammatory responses.
The study aims to elucidate the anti-inflammatory effect and mechanism of Roseburia intestinalis (R. intestinalis) in Crohn's disease (CD). 16S-rRNA genome sequencing technique is used to detect the characteristics of intestinal microbiota in untreated CD patients and healthy controls. Then the study investigates the effects of R. intestinalis on disease activity index score, intestinal pathology, the differentiation of Treg cells, and the expressions of Thymic stromal lymphopoietin (TSLP), TGF-β and IL-10 by using TNBS colitis models. At the cellular level, the study uses LPS to stimulate Caco-2 cells to conduct inflammation models and then co-culture with R. intestinalis and detect changes of TSLP and TGF-β. The study then uses R. intestinalis to stimulate peripheral blood mononuclear cells, and the change of Treg cells was detected. Genome sequencing of fecal samples from untreated CD patients (n = 10) revealed decreases in the abundance and diversity of intestinal microbiota, including R. intestinalis. Moreover, R. intestinalis reduced disease activity index scores, colon shortening, intestinal mucosal epithelial injury, and mucosal lymphocyte infiltration in a colitis mice model. It suppressed intestinal inflammation by increasing Treg cell numbers and expression of the anti-inflammatory cytokines TSLP, TGF-β, and interleukin-10 (P < 0.05). R. intestinalis also increased secretion of TSLP and TGF-β in lipopolysaccharide-treated Caco-2 cells. These findings suggest that R. intestinalis suppresses CD pathogenesis by inducing anti-inflammatory responses.


Distal enlargement of the optic nerve sheath in the hyperacute stage of intracerebral haemorrhage.
Optic nerve sheath diameter (ONSD) enlargement is detectable in patients with increased intracranial pressure. The aim was to detect an enlargement of the ONSD using optic nerve sonography in patients with acute intracerebral haemorrhage (ICH) within 6 h of the onset of symptoms. Thirty-one acute ICH patients, 15 age-matched acute ischaemic stroke patients and 16 age-matched healthy volunteers were enrolled consecutively in this prospective bi-centre observational study. All acute stroke patients underwent brain CT, optic nerve sonography and transcranial colour-coded duplex sonography (TCCS) at admission within 6 h of stroke onset. The ONSD both 3.0 and 12.0 mm behind the globe using optic nerve sonography were recorded and statistically evaluated, as were age, sex, haemorrhage volume and midline shift measured by CT, and blood flow velocities in both middle cerebral arteries using TCCS. In acute ICH patients, a significant enlargement of ONSD was detected (p < 0.0083). The best cut-off point to predict ICH volume >2.5 cm³ was the relative ONSD enlargement of > 0.66 mm (> 21 %), with 90.3% accuracy and kappa coefficient 0.760 (95% CI 0.509 to 1.000). Sonographically measured enlargement of the ONSD may already be detectable in the hyperacute stage of increased intracranial pressure.


Global expression study in colorectal cancer on proteins with alkaline isoelectric point by two-dimensional difference gel electrophoresis.
Colorectal cancer is one of the leading causes of cancer death worldwide. To identify candidates for biomarkers and therapeutic targets, we investigated the proteome of colorectal cancer tissues. Using 2D-DIGE in combination with our original large format electrophoresis apparatus, we compared surgically resected normal and tumor tissues from 53 patients with colorectal cancer. We focused on proteins with an alkaline pI using IPG gels for the alkaline range. We observed 1687 protein spots, and found 100 spots with statistical (p<0.01) and significant (>2-fold) differences between the normal and the tumor tissue groups. Among these 100 protein spots, five showed a different intensity between tumor tissues from the stage-II and the stage-III patients. MS experiments revealed that these 100 protein spots corresponded to 58 unique proteins. These included six proteins which had not been previously reported to be associated with colorectal cancer. Among these proteins, five were not reported in any type of malignancy. IEF/western blotting confirmed the differences in protein expression between the normal and the tumor tissues. These results may provide an insight for biomarker development and drug target discovery in colorectal cancer.


In situ hybridization in the study of remodeling in proliferative glomerulonephritis.
In situ hybridization combined with immunohistochemistry provides a powerful tool to study the temporal and spatial relationships between cellular sources of mRNA and localization of translated protein in normal biologic and pathologic processes. In this symposium, techniques in probe selection for the detection of mRNA in normal kidney and renal disease were discussed. Examples of the application of in situ hybridization in the study of renal disease were demonstrated using a model of proliferative glomerulonephritis induced by habu snake venom. This model follows an accelerated course of remodeling involving mesangial cell migration, proliferation, and extracellular matrix synthesis. The cellular sources and temporal expression of 2 adhesive proteins, fibronectin and thrombospondin, known to have a role in cell remodeling during embryogenesis and wound healing, were examined and compared to mesangial cell behaviors during the course of habu venom-induced glomerulonephritis. Mesangial cell migration in early lesions was associated with thrombospondin and fibronectin derived from platelets or macrophages. Thrombospondin mRNA and protein peaked at 48 hr after habu venom and were associated with mesangial cell proliferation; but thrombospondin mRNA and protein declined at 72 hr when expression of collagen type IV and laminin mRNA and protein peaked. Mesangial cell expression of fibronectin first appeared at 48 hr, and peaked at 72 hr after habu venom. Thus, mesangial cell migration was associated with exogenous fibronectin and thrombospondin derived from platelets or macrophages. Mesangial cell expression of thrombospondin was associated with migration and proliferation, whereas, expression of fibronectin was associated with proliferation and matrix synthesis. These results suggest distinctive temporal and spatial roles for thrombospondin and fibronectin in remodeling during glomerulonephritis and illustrate the utility of in situ hybridization and immunohistochemistry in the detection of cellular sources of translated proteins.


Chemiluminescence and antioxidant levels during peroxisome proliferation by fenofibrate.
Fenofibrate, the hypolipidemic drug and peroxisome proliferator, was given to mice (0.23% w/w in the diet) during 1-3 weeks and H2O2 and TBARS steady state concentrations, liver chemiluminescence and antioxidant levels were measured. Administration of fenofibrate during 2 weeks induced an increase of 89% in H2O2 steady state concentration. Spontaneous chemiluminescence was decreased by 57% during fenofibrate treatment, while no significant effect was observed on TBARS concentration. Hydroperoxide-initiated chemiluminescence was decreased by 56% after 15 days of fenofibrate treatment, probably due to an increase in endogenous antioxidant levels. Total and oxidized glutathione increased gradually after fenofibrate administration, obtaining maximal increases of 67% and 58% respectively, after 22 days of treatment. An increase of 55% was found in ubiquinol levels in treated mice, as compared with the controls. alpha-tocopherol content was decreased by 51% in the liver of fenofibrate-treated mice. According to our findings, the high rate of H2O2 production associated with peroxisome proliferation, would not lead to an increase in lipid peroxidation. This can be explained by the presence of high levels of ubiquinols, which act as an antioxidant. The increased production of H2O2, would lead to DNA damage directly, and not through lipid peroxidation processes.


Surveillance of antimicrobial resistance in the United Arab Emirates: the early implementation phase.
National surveillance of antimicrobial resistance (AMR) is an important public health function. Published national AMR surveillance data from the Middle East/North Africa (MENA) region is scarce. This paper describes the early implementation phase of establishing AMR surveillance in the United Arab Emirates (UAE). Building on the existing AMR surveillance system in the Emirate of Abu Dhabi, and adopting the WHO-GLASS methodology, the UAE Ministry of Health and Prevention (MOHAP) established the national AMR Surveillance program in 2015, in collaboration with regional health authorities and healthcare providers. Main objectives of this program are to (a) set AMR surveillance standards, (b) collect and analyze AMR surveillance data for common bacterial and fungal infections, (c) report on AMR levels and trends in the UAE, (d) strengthen local and national capacity for AMR surveillance, and (e) support AMR prevention and control strategies in the UAE. AMR surveillance data is collected through a network of 317 surveillance sites (including 84 hospitals and 233 centers/clinics), and 45 microbiology labs across all seven Emirates of the UAE. Surveillance of antimicrobial resistance has been successfully established since 2010 in the UAE. A national AMR surveillance protocol has been developed, adopting the WHO GLASS protocol. Extensive capacity-building and training activities have strengthened the local and national capacity for AMR surveillance. Between 2010 and 2021, a network of 317 surveillance sites and 45 laboratories have reported a total of 1,277,080 isolates from 662,065 non-duplicate patients to the national level. AMR data is reported annually by MOHAP through a National AMR surveillance report. National AMR data is utilized for informing the development of standard treatment guidelines at national level. National surveillance of antimicrobial resistance has been successfully established in the United Arab Emirates, allowing to monitor levels and trends of antimicrobial resistance for common bacterial and fungal pathogens, and detecting emerging resistance. The availability of such national AMR surveillance data allows for the first time to inform the development of national standard treatment guidelines for empiric treatment of common bacterial and fungal infections in the UAE.


Ischaemic stroke in anticoagulated patients with atrial fibrillation.
Anticoagulation substantially reduces the risk of stroke in patients with atrial fibrillation (AF). However, recent studies have shown that up to 22%-36% of patients on anticoagulation will suffer an ischaemic stroke (IS). In this narrative review, we provide an overview of risk factors, mechanisms, management of acute IS and strategies for secondary prevention for patients with AF with stroke despite oral anticoagulation. For this paper, we reviewed available literature from important studies (randomised clinical trials, meta-analyses, reviews and case series) on patients with IS despite anticoagulation. We focused on recent studies that examined safety and efficacy of acute stroke treatments and evaluation and management strategies for secondary prevention. The literature review suggests that patients with AF with IS despite anticoagulation are a heterogeneous group with several possible mechanisms, which may include reduced or non-adherence to anticoagulation, competing non-cardioembolic stroke aetiologies or cardioembolic mechanisms separate from AF. The identification of one or more possible mechanisms of stroke despite anticoagulation may allow for a more targeted and individualised approach for secondary prevention. There are limited data to guide management in such patients, and strategies to prevent recurrent strokes include strict risk factor control and therapies targeting the most likely stroke mechanism. In cases where AF is suspected to be the culprit, clinical trials are needed to test the safety and efficacy of left atrial appendage occlusion plus anticoagulation versus continued anticoagulation alone.


[Non-obstructive coronary artery disease documented by cardiac computed tomography: Discrepancy between atherosclerotic burden and cardiovascular risk].
Cardiac computed tomography (CT) documents the presence of coronary artery disease, regardless of the degree of stenosis. The prognostic value of non-obstructive coronary artery disease documented by cardiac CT has recently been validated. However, there are still no clear guidelines on the management of such patients, particularly concerning initiation of more aggressive pharmacological measures for primary prevention. The approach to these patients remains controversial, especially in cases in which there is a discrepancy between cardiovascular risk and the atherosclerotic burden as documented by cardiac CT. The authors describe the case of a patient with a discrepancy between the extent of documented coronary atherosclerosis and that estimated according to pretest probability and cardiovascular risk scores. As this individual had more severe coronary atherosclerosis than expected (calcium score above the 90th percentile and non-obstructive coronary artery disease on cardiac CT) but was a competitive athlete and otherwise asymptomatic and without risk factors or cardiovascular history, with a very low estimated cardiovascular risk, it was difficult to decide on the risks and benefits of pharmacological primary prevention.


Lens-based theory of the Lau effect.
A new theoretical model of the Lau effect is presented. The transmittance of a diffraction grating can be expressed in an equivalent form as the sum of transmittances of thin cylindrical lenses. Therefore it is possible to explain the Lau effect on the basis of the well-known imaging properties of lenses. According to the given approach, the Lau fringes are created by overlapped images of the first grating that are formed by a set of lenses corresponding to the second grating in the setup. The theory leads to an exhaustive description of the Lau-effect parameters. In particular, one can indicate the shape of the Lau fringes and localize planes of the fringes dependent on the axial distance between gratings and their periods.


Contactpoint analysis of the HeLa nuclear factor I recognition site reveals symmetrical binding at one side of the DNA helix.
Nuclear factor I (NFI) is a HeLa sequence-specific DNA-binding protein that is required for initiation of adenovirus (Ad) DNA replication and may be involved in the expression of several cellular genes. The interaction between NFI and its binding site on the Ad2 origin has been studied. Methylation interference and protection, u.v. irradiation of 5-BrdU substituted DNA and ethylation interference revealed major groove contacts with G and T, and phosphate backbone contacts. Computer stereographics show that the contacts are located in two blocks showing dyad symmetry to each other and 22 out of 23 contacts are accessible from one side of the helix. Inversion of the NFI binding site did not change the NFI dependent stimulation of Ad2 DNA replication in a reconstituted system. All data are compatible with NFI binding as a dimer at one side of the DNA helix.


Cooperation of the inducible nitric oxide synthase and cytochrome P450 1A1 in mediating lung inflammation and mutagenicity induced by diesel exhaust particles.
Diesel exhaust particles (DEPs) have been shown to activate oxidant generation by alveolar macrophages (AMs), alter xenobiotic metabolic pathways, and modify the balance of pro-antiinflammatory cytokines. In this study we investigated the role of nitric oxide (NO) in DEP-mediated and DEP organic extract (DEPE) -mediated inflammatory responses and evaluated the interaction of inducible NO synthase (iNOS) and cytochrome P450 1A1 (CYP1A1). Male Sprague-Dawley rats were intratracheally (IT) instilled with saline, DEPs (35 mg/kg), or DEPEs (equivalent to 35 mg DEP/kg), with or without further treatment with an iNOS inhibitor, aminoguanidine (AG; 100 mg/kg), by intraperitoneal injection 30 min before and 3, 6, and 9 hr after IT exposure. At 1 day postexposure, both DEPs and DEPEs induced iNOS expression and NO production by AMs. AG significantly lowered DEP- and DEPE-induced iNOS activity but not the protein level while attenuating DEPE- but not DEP-mediated pulmonary inflammation, airway damage, and oxidant generation by AMs. DEP or DEPE exposure resulted in elevated secretion of both interleukin (IL) -12 and IL-10 by AMs. AG significantly reduced DEP- and DEPE-activated AMs in IL-12 production. In comparison, AG inhibited IL-10 production by DEPE-exposed AMs but markedly increased its production by DEP-exposed AMs, suggesting that NO differentially regulates the pro- and antiinflammatory cytokine balance in the lung. Both DEPs and DEPEs induced CYP1A1 expression. AG strongly inhibited CYP1A1 activity and lung S9 activity-dependent 2-aminoanthracene mutagenicity. These studies show that NO plays a major role in DEPE-induced lung inflammation and CYP-dependent mutagen activation but a lesser role in particulate-induced inflammatory damage.


Whole-body Vibration Training in Frail, Skilled Nursing Home Residents.
Frailty is a geriatric syndrome characterized by diminished muscle strength, endurance, and weakened physical function. Physical frailty is often unaddressed clinically as it tends to manifest among chronic illnesses and sarcopenia, and consensus criteria for frailty diagnosis remains elusive. Whole-body vibration training (WBVT) has been used to improve deficits in lower body muscular strength and functional performance in healthy and high functioning older adults; therefore, the purpose of this study was to determine the effects of WBVT on physical frailty in skilled nursing home residents. This study compared the effects of 12 wks (2x/wk) of WBVT (n = 10) to standard care, which served as the control (CON: n = 10), on isometric knee extension strength (KE), body composition, and functional performance in 20 (16 female) pre-frail and frail skilled nursing home residents (82 ± 5 yrs). Frailty was assessed using the FRAIL scale and function was measured using the short physical performance battery (SPPB). WBVT consisted of 4 lower body exercises (partial squat, narrow squat, wide squat, calf raise) during vertical vibration (25 - 40 Hz). Data were analyzed using two-way ANOVA (group × time) and post-hoc paired and independent t-tests. Significance was set at p ≤ 0.05. There were significant group-by-time interactions for KE and SPPB. Post-hoc paired t-tests revealed that WBVT improved KE (22.3 ± 4.0 to 29.0 ± 4.5 kg) and improvement in SPPB performance approached significance (4.5 ± 2.3 to 5.2 ± 2.1 units, p = 0.089). WBVT was well tolerated and occurred without adverse health complications. WBVT can be used to counteract losses in leg strength without adverse health complications in skilled nursing home residents.


Smartphone Use among Anesthesiologists during Work Hours: A Survey-Based Study.
Smartphone use has revolutionized life in all spheres, including the medical field. Smartphones provide immense opportunities but may also lead to negative consequences due to the element of distraction. In the medical profession and more so among anesthesiologists, multitasking has become very common, but the presence of mind is equally important. This study attempts to analyze the smartphone practices and trends among anesthesiologists during work hours in our country. The study aimed to identify recent trends and practices of smartphone use among anesthesiologists during working hours and its distribution as per designation and institutions. It also intends to determine the purposes of smartphones and their impact on patient care. Online survey consisting of open-ended multiple-choice questions was conducted and circulated as Google Forms via E-mail and WhatsApp. This survey was conducted to compare the respondents' views as per designation and workplace distribution. In addition, participants were asked about the current practices in smartphone use at their workplace, purposes of use, time spent on smartphones, and any negative medical consequences faced due to the same. One-way ANOVA test was used to compare the means between the groups. Chi-square test/Fisher's exact test was used to compare the proportions. Two hundred and sixteen (54%) were resident doctors, whereas 184 (46%) were consultants. Most of the respondents were young, with a mean age around 36 years. 31.5% of the residents used smartphones very often during anesthetized patient care compared to 10.3% of the consultants. Purposes of using smartphones were multiple, with phone calls (100%) being the most common followed by WhatsApp messaging (79.2%). 86.1% of the residents, as compared to 61% of the consultants, had anesthesia/intensive care unit-related apps on their smartphones. There was almost an equivocal response to how the smartphone has impacted patient care. 50.9% of the residents and 43% of the consultants felt improved patient care, whereas 38% of the residents and 43.5% of the consultants believed it had worsened. There was no clear-cut consensus whether smartphone use improved or worsened patient care. On the one hand, there can be distractions leading to adverse medical consequences, while on the other hand, the use of medical apps has been made possible because of the handy and easily accessible smartphones. Thus, the use of smartphones may be carried out with a sense of responsibility by the anesthesiologists during work hours.


The genomic structure of human V beta 6 T cell antigen receptor genes.
Six genomic clones were characterized containing members of the human V beta 6 subfamily of T cell antigen receptor genes. There were four major findings. (a) New V beta genes were discovered, including V beta 6.10, V beta 13.4, V beta 13.5, and V beta 5.5. (b) Members of the V beta 13, V beta 6, and V beta 5 subfamilies cluster together in the V beta locus and may have evolved through multiple duplication events of an ancestral cassette containing V beta 13-V beta 6-V beta 5 genes. These V beta subfamilies are used by an estimated one-third of T cells in humans and probably represent a highly useful component of the V beta repertoire. (c) The promoters of V beta 13, V beta 6, and V beta 5 genes contain conserved decamer motifs, but discrete differences were observed between promoters of different V beta subfamilies, raising the question of different transcriptional control depending on V beta subfamily usage. (d) The new V beta 6.10 gene is probably a pseudogene, which may have been inactivated due to retrotransposition of Alu elements into its promoter region, a mutation affecting a highly conserved cysteine residue or mutations of the 3' recombinase signal sequence.


PointFinder: a novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens.
Antibiotic resistance is a major health problem, as drugs that were once highly effective no longer cure bacterial infections. WGS has previously been shown to be an alternative method for detecting horizontally acquired antimicrobial resistance genes. However, suitable bioinformatics methods that can provide easily interpretable, accurate and fast results for antimicrobial resistance associated with chromosomal point mutations are still lacking. Phenotypic antimicrobial susceptibility tests were performed on 150 isolates covering three different bacterial species: Salmonella enterica, Escherichia coli and Campylobacter jejuni. The web-server ResFinder-2.1 was used to identify acquired antimicrobial resistance genes and two methods, the novel PointFinder (using BLAST) and an in-house method (mapping of raw WGS reads), were used to identify chromosomal point mutations. Results were compared with phenotypic antimicrobial susceptibility testing results. A total of 685 different phenotypic tests associated with chromosomal resistance to quinolones, polymyxin, rifampicin, macrolides and tetracyclines resulted in 98.4% concordance. Eleven cases of disagreement between tested and predicted susceptibility were observed: two C. jejuni isolates with phenotypic fluoroquinolone resistance and two with phenotypic erythromycin resistance and five colistin-susceptible E. coli isolates with a detected pmrB V161G mutation when assembled with Velvet, but not when using SPAdes or when mapping the reads. PointFinder proved, with high concordance between phenotypic and predicted antimicrobial susceptibility, to be a user-friendly web tool for detection of chromosomal point mutations associated with antimicrobial resistance.