DNA-protein interactions and bacterial chromosome architecture.
Bacteria, like eukaryotic organisms, must compact the DNA molecule comprising their genome and form a functional chromosome. Yet, bacteria do it differently. A number of factors contribute to genome compaction and organization in bacteria, including entropic effects, supercoiling and DNA-protein interactions. A gamut of new experimental techniques have allowed new advances in the investigation of these factors, and spurred much interest in the dynamic response of the chromosome to environmental cues, segregation, and architecture, during both exponential and stationary phases. We review these recent developments with emphasis on the multifaceted roles that DNA-protein interactions play.


Direct interaction of surfactant protein A with myometrial binding sites: signaling and modulation by bacterial lipopolysaccharide.
Surfactant protein A (SFTPA1), a member of the collagenous lectin (collectin) family, was first described as a major constituent of lung surfactant, but has recently also been found in the female genital tract. Various microorganisms colonize this area and may cause intrauterine infection or trigger preterm labor. We found that SFTPA1 was not produced in the uterus. Instead, it was immunodetected transiently in rat myometrium at the end (Days 19 and 21) of gestation, but not postpartum, and in cultured myometrial cells. Fluorescence microscopy showed that Texas Red-labeled SFTPA1 bound to myometrial cells. This result was confirmed by biochemical approaches. [(125)I]-SFTPA1 bound to two myometrial cell proteins (55 and 210 kDa). This interaction was dependent on the integrity of the collagenlike domain of SFTPA1. SFTPA1 rapidly activated mitogen-activated protein kinase 1/3 (MAPK1/3) in myometrial cells. Bacterial lipopolysaccharide (LPS), an agent known to trigger uterine contractions and preterm birth, also activated MAPK1/3. The prolonged treatment of myometrial cells with LPS or SFTPA1 upregulated PTGS2 (COX2) protein levels. The addition of rough-type LPS to SFTPA1 blocked the interaction of SFTPA1 with its binding sites and the activation of MAPK1/3 and PTGS2 by SFTPA1. Our data provide the first demonstration of a direct effect of SFTPA1 on rat myometrial cells and inhibitory cross talk between SFTPA1 and LPS signals, providing new insight into the mechanisms of normal and preterm parturition.


The role of CDH2 and MCP-1 mRNAs of blood extracellular vesicles in predicting early-stage diabetic nephropathy.
Extracellular vesicles (EVs), including exosomes and microvesicles, are involved in intercellular communication by transferring biomolecules such as mRNA, which has been shown to be as essential biomarkers for many physiological and pathological conditions such as diabetic nephropathy (DN). This study aimed to investigate the expression of CDH1, CDH2, MCP-1, and PAI-1 mRNAs in blood EVs of DN patients and to determine their accuracy in predicting early-stage DN. We recruited 196 participants, including 35 overt DN patients, 53 incipient DN patients, 62 diabetic patients (DM), and 46 healthy individuals. Quantification of the mRNA profile of blood EVs was performed using the qRT-PCR method. The diagnostic performance of mRNA was evaluated using receiver operating characteristic analysis. The mRNA expression of CDH2 and MCP-1 was downregulated in overt DN group (0.22-fold change and 0.15-fold change, respectively) and incipient DN group (0.60-fold change and 0.43-fold change, respectively) compared to DM group (1.72-fold change and 2.77-fold change, respectively), while PAI-1 mRNA expression decreased in incipient DN group (0.70-fold change) and DM group (0.58-fold change) compared to control. However, the expression level of CDH1 mRNA was not significantly different among the four groups (p = 0.408). Moreover, CDH2 and MCP-1 mRNAs inversely correlated with creatinine (r = -0.370 and r = -0.361, p<0.001) and Alb/Cr ratio (r = -0.355 and r = -0.297, p<0.001). 1/CDH2 mRNA also predicted overt DN with an accuracy of 0.75 (95%CI: 0.65-0.85) and incipient DN with an accuracy of 0.61 (95%CI: 0.50-0.71) while 1/MCP-1 mRNA had an accuracy of 0.66 (95%CI: 0.55-0.77) for overt DN prediction and an accuracy of 0.61 (95%CI: 0.51-0.71) for incipient DN prediction. CDH2 and MCP-1 mRNAs expression in blood EVs was decreased with the development of DN, suggesting the renoprotective effect of these mRNAs in diabetic individuals. Moreover, their quantifications could serve as diagnostic biomarkers for early-stage DN.


Cell line specific radiosensitizing effect of zalcitabine (2',3'-dideoxycytidine).
The potential of zalcitabine (ddC) to act as an ionizing radiation response modifier was tested on exponentially growing human cancer cells in vitro. Two human cell lines, WiDr (colon) and MCF-7 (breast) were exposed to ddC at 10 microM concentration for various lengths of time (18, 24, 48 and 72 h). On the WiDr cell line the dual effect of concentration and duration of exposure prior to irradiation was investigated. Experimental endpoints were clonogenicity and viability, as measured by colony formation assay (CFA) and MTT assay respectively. The impact on cell-cycle distribution prior to irradiation was assessed by flow cytometry using a double labeling technique (propidium iodide and bromodeoxyuridine pulse label). A significant reduction in surviving fraction and viability was observed for WiDr-cells irradiated after pre-exposure to 10 microM for 18, 48 and 72 h as compared to corresponding irradiated controls. At lower concentrations (1 and 5 microM), the radiosensitizing effect was only significant after a 72-h exposure (assessed by CFA). For MCF-7, ddC induced a significant modification of the dose response only with 24 and 48 h preincubation. However, the overall effect was less pronounced as compared to WiDr. Cell-cycle analysis showed accumulation in S-phase, 48 and 72 h after treatment with 10 microM ddC in the WiDr cells, with a progressive shift to late S-phase as shown by the biparametric analysis. The degree of radiosensitization is cell-line dependent with the most important sensitization observed on the most "radioresistant cell line", i.e., the cell line with the lowest alpha value and highest SF 2 (WiDr). For WiDr, radiosensitization by ddC depends on the duration of exposure and the concentration of the drug.


High-Loading Pt Single-Atom Catalyst on CeO2 -Modified Diatomite Support.
Single-atom catalysis has become a new branch in heterogeneous catalysis. Although the naturally produced SiO2 -based materials are abundant and stable, fabrication of single-atom catalysts on such supports with high loading remains as a formidable challenge due to the lack of bonding sites to anchor the isolated metal species. Herein, modifying the diatomite, a kind of pure SiO2 mineral, with CeO2 nanoparticles is demonstrated to increase the defect sites on the support. The enhanced metal-support interaction maintains the atomic dispersion of Pt species with above 1 wt.% loading, exhibiting good performance in the selective hydrogenation of phenylacetylene to styrene.


The complete organellar genomes of the entheogenic plant Psychotria viridis (Rubiaceae), a main component of the ayahuasca brew.
Psychotria viridis (Rubioideae: Rubiaceae), popularly known as chacrona, is commonly found as a shrub in the Amazon region and is well-known to produce psychoactive compounds, such as the N,N-dimethyltryptamine (DMT). Together with the liana Banisteropsis caapi, P. viridis is one of the main components of the Amerindian traditional, entheogenic beverage known as ayahuasca. In this work, we assembled and annotated the organellar genomes (ptDNA and mtDNA), presenting the first genomics resources for this species. The P. viridis ptDNA exhibits 154,106 bp, encoding all known ptDNA gene repertoire found in angiosperms. The Psychotria genus is a complex paraphyletic group, and according to phylogenomic analyses, P. viridis is nested in the Psychotrieae clade. Comparative ptDNA analyses indicate that most Rubiaceae plastomes present conserved ptDNA structures, often showing slight differences at the junction sites of the major four regions (LSC-IR-SSC). For the mitochondrion, assembly graph-based analysis supports a complex mtDNA organization, presenting at least two alternative and circular mitogenomes structures exhibiting two main repeats spanning 24 kb and 749 bp that may symmetrically isomerize the mitogenome into variable arrangements and isoforms. The circular mtDNA sequences (615,370 and 570,344 bp) encode almost all plant mitochondrial genes (except for the ccmC, rps7, rps10, rps14, rps19, rpl2 and rpl16 that appears as pseudogenes, and the absent genes sdh3, rps2, rsp4, rsp8, rps11, rpl6, and rpl10), showing slight variations related to exclusive regions, ptDNA integration, and relics of previous events of LTR-RT integration. The detection of two mitogenomes haplotypes is evidence of heteroplasmy as observed by the complex organization of the mitochondrial genome using graph-based analysis. Taken together, these results elicit the primary insights into the genome biology and evolutionary history of Psychotria viridis and may be used to aid strategies for conservation of this sacred, entheogenic species.


In vitro and in vivo activities of acylated derivatives of isoniazid against mycobacterium tuberculosis.
Enzymatic acylation of the antitubercular isoniazid (INH) by N-acetyl transferases reduces the therapeutic effectiveness of the drug. Because it represents a major metabolic pathway for INH in human beings, such acetylation has serious consequences for tuberculosis treatment regimens. Among patients in whom this process is efficient, the "rapid acetylators," the resultant chronic underdosing of INH may give rise to the development of resistance, as well as inadequate therapy. Not much work has been done previously to characterize the antitubercular properties of other N2-acylisoniazids. In order to address the fundamental issue of the activities of these acylated derivatives of INH, a number of such compounds 1a-f were chemically synthesized for investigation by a method providing good yield and purity. In experiments in vitro against Mycobacterium tuberculosis, these compounds displayed minimum inhibitory concentration (MIC) values between several fold and several hundred fold greater than that of INH itself, on a molar basis, with some of the more active compounds having higher calculated values of log P. Among these derivatives, compound 1b, closely homologous to the INH metabolite 1a, N2-acetylisoniazid, provided unexpected protection in tuberculosis-infected mice. The authors conclude that such close structural congeners of metabolites of INH may serve as significant leads in antitubercular drug discovery and in the exploration of the mode of action of INH.


Identification of the SRC-family tyrosine kinase HCK as a therapeutic target in mantle cell lymphoma.
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma subtype arising from naïve B cells. Although novel therapeutics have improved patient prognosis, drug resistance remains a key problem. Here, we show that the SRC-family tyrosine kinase hematopoietic cell kinase (HCK), which is primarily expressed in the hematopoietic lineage but not in mature B cells, is aberrantly expressed in MCL, and that high expression of HCK is associated with inferior prognosis of MCL patients. HCK expression is controlled by the toll-like receptor (TLR) adaptor protein MYD88 and can be enhanced by TLR agonists in MCL cell lines and primary MCL. In line with this, primary MCL with high HCK expression are enriched for a TLR-signaling pathway gene set. Silencing of HCK expression results in cell cycle arrest and apoptosis. Furthermore, HCK controls integrin-mediated adhesion of MCL cells to extracellular matrix and stromal cells. Taken together, our data indicate that TLR/MYD88-controlled aberrant expression of HCK plays a critical role in MCL proliferation and survival as well as in retention of the malignant cells in the growth- and survival-supporting lymphoid organ microenvironment, thereby contributing to lymphomagenesis. These novel insights provide a strong rationale for therapeutic targeting of HCK in MCL.


Chemosensitivity testing for gastrointestinal cancer: survival benefit potential and limitations.
Chemosensitivity testing is considered by some to be a useful method for predicting drug sensitivity of tumor tissues after surgery for gastrointestinal cancer. Although survival benefit is not fully established, several chemosensitivity testing methods have been used clinically, both in the selection of adjuvant therapy and in the treatment of metastatic disease. Chemosensitivity testing is used not only for determination of drug resistance, but also for determination of drug sensitivity conferring a potential survival benefit. Previous retrospective correlation studies showed survival of patients treated with a 'tested' drug to be superior to that of patients treated with a standard drug, but the clinical benefit of chemosensitivity testing in comparison to surgical therapy alone or standard chemotherapy has not been documented in a randomized controlled trial. The clinical usefulness of individualized versus standard therapy needs to be determined. Here we discuss the potential survival benefit and current limitations of chemosensitivity testing in patients with gastrointestinal cancer.


A Novel Case of Fibroids after Menopause.
Fibroids are a condition commonly seen as part of routine gynaecological practice and generally present with menorrhagia, infertility, or pressure symptoms depending on their exact location. We report the case of a postmenopausal 57-year-old lady presenting with left-sided pain and frequency with a complex 15 cm mass mid pelvis and an adjacent additional 7 cm cyst but a risk of malignancy index suggesting benign pathology. She underwent total abdominal hysterectomy (TAH) and right-sided salpingo-oophrectomy (RSO) on recommendation of the multidisciplinary team (MDT) and histology confirmed leiomyomatosis peritonealis disseminata. This rare but important condition is often confused with peritoneal carcinomatosis on imaging. The mainstay of treatment involves lesion and omental excision followed by removal of hormonal stimuli although this approach must be personalised as many younger women may wish to retain their uteri. Long-term follow-up is essential due to the potential for malignant transformation.


Advanced drill technology in treatment of congenital choanal atresia.
Congenital choanal atresia is a challenging clinical problem requiring prompt diagnosis and intervention. The method of repair is controversial, with no technique having gained universal acceptance. Proponents of the transnasal repair must acknowledge the variability of results, especially with thick bony plates, and the technical difficulties associated with this method. Advocates of the transpalatal route must recognize the associated morbidity of this technique in the newborn. The adaptation of the endoscopic technique and the development of new powered instrumentation have significantly improved the transnasal technique so that safe controlled repair may now be accomplished in the newborn.


Transitioning to Telehealth During the COVID-19 Pandemic: Patient Perspectives and Attendance at an HIV Clinic in San Francisco.
Approximately 1.2 million people are living with HIV in the United States, with 16,000 in San Francisco. Many HIV-positive individuals have difficulty maintaining follow-up clinic visits under normal circumstances, and this is complicated by the coronavirus disease 2019 (COVID-19) pandemic as many institutions transition to a telehealth-focused model of care to maintain patient and provider safety. However, it was unknown how telehealth would impact patient attendance and perceptions about their care, particularly in populations at high risk of appointment nonattendance. To quantify the impact of telehealth on retention in care for a vulnerable HIV-infected population and to identify patient perspectives of telehealth and its effect on appointment attendance, we studied patients at the University of California, San Francisco (UCSF) 360 Wellness Center, an HIV primary care clinic in urban San Francisco, California. Anonymous surveys were conducted to assess patient perceptions of telehealth, and 21% of patients sent surveys responded. Appointment attendance rates for all visits were analyzed before and after the shelter-in-place order in San Francisco on March 16, 2020. With the transition to telehealth, the overall nonattendance rate decreased by ∼3%. Most common perceived strengths of telehealth included convenience and safety, whereas disadvantages included technical barriers and unfamiliarity. Despite barriers and disadvantages listed by patients, a majority are willing to attend telehealth visits, as 80.5% of respondents reported being equally or more likely to attend telehealth visits. This is a critical finding during the COVID-19 pandemic and beyond; we believe that telehealth can improve appointment attendance for vulnerable populations who often face barriers to receiving health care.


[The head-body index used to access femoral head size].
Basing on an analysis of 260 X-rays of healthy hip joints in children and adults the authors present a head-body index (according to Kruczyński), used to assess femoral head size. The index is defined as the ratio of the circumference of circle drawn around the femoral head to the body width of the femur (measured below the minor trochanter). In patients less than 17 years old the index was 170 (SD-14.6).


Anticonvulsant activity of Dorema ammoniacum gum: evidence for the involvement of benzodiazepines and opioid receptors.
This study investigated the anticonvulsant activity and possible mechanism of action of an aqueous solution of Dorema ammoniacum gum (DAG) which has been used traditionally in the treatment of convulsions. In this study, the anticonvulsant activity of DAG was examined using the pentylentetrazole (PTZ) model in mice. Thirty male albino mice were divided randomly and equally to 5 groups, and pretreated with normal saline, diazepam, or various doses of DAG (500, 700, and 1000 mg/kg, i.p.), prior to the injection of PTZ (60 mg/kg, i.p.). The latency and duration of seizures were recorded 30 min after PTZ injection. Pretreatments with naloxone and flumazenil in different groups were studied to further clarify the mechanisms of the anticonvulsant action. Phytochemical screening and thin layer chromatography (TLC) fingerprinting of ammoniacum gum was also determined. DAG showed significant anticonvulsant activity at all doses used. The gum delayed both the onset and the duration of seizures induced by PTZ. Treatment with flumazenil before DAG (700 mg/kg) inhibited the effect of gum on seizure duration and latency to some extent and administration of naloxone before DAG also significantly inhibited changes in latency and duration of seizure produced by DAG. The percentage inhibition was greater with naloxone than with flumazenil. This study showed that DAG had significant anticonvulsant activity in PTZ-induced seizures, and GABAergic and opioid systems may be involved. More studies are needed to further investigate its detailed mechanism.


[Correlative study of distribution of brain tumor stem cell with micro-vascular system].
To investigate the expressions of putative brain tumor stem cell (BTSC) marker CD133, Nestin and blood vessel endothelial cell marker CD31 in 65 cases of formalin fixed paraffin embedded gliomas. The relationship of BTSC distribution with micro-blood vessels was analyzed using morphometry. (1) The expression levels of Nestin and CD133 proteins were detected using SABC immunohistochemical analysis. Then we calculated the percentage of CD133(+) cells, CD133(+) blood vessels, Nestin(+) cells and Nestin(+) blood vessels among 65 tumors, grade II (n = 18), grade III (n = 23) and grade IV (n = 24), according to WHO 2000 classification of nervous system tumors. (2) Double immunofluorescence staining was used to detect the co-expressions of CD133/CD31, CD133/Nestin and Nestin/CD31. Then the correlation of two different marked cells with the corresponding positive vascular endothelial cells were determined. CD133(+) cells and Nestin(+) cells could be observed in all glioma tissues. Furthermore they could also be observed expressing in the endothelial cells. In low-grade group, there were fewer CD133(+) blood vessels or Nestin(+) blood vessels in the regions which CD133(+)cells or Nestin(+) cells distributed compared with the high-grade group. The CD133(+)/CD31(+) and Nestin(+)/CD31(+) cells could be found co-expressed in the endothelial cells by using double immunofluorescence staining. Positive correlation was observed between the CD133(+) cells and CD133(+) blood vessels (r = 0.945, P < 0.01). It was similar to the correlation between the Nestin(+) blood vessels and Nestin(+) cells (r = 0.727, P < 0.01). In gliomas, the endothelial cells express brain tumor stem cells markers. Therefore the capillaries in gliomas may come from the differentiation of BTSCs. And the BTSCs are accumulated around the capillaries. Along with the rank of tumor grades, positive correlation is observed between CD133(+) cells or Nestin(+) cells with the corresponding blood vessels.


A review of Australian health privacy regulation regarding the use and disclosure of identified data to conduct data linkage.
To review Australian legislation about privacy, focusing on provisions within the regulations to conduct health research using identified data and lobby for regulatory change in the ACT. A systematic review of Commonwealth and jurisdiction health privacy regulation. Australia has a number of regulations for the protection of privacy of health information. In addition to Commonwealth privacy laws, there are jurisdictional regulations concerning protection of health information. These range from no specific legislation in Western Australia, to a code of practice in South Australia, and Commonwealth legislation that deals with use and disclosure of identified health information to conduct health research (Sections 95 and 95A of the Privacy Act 1988). At the time of this review, all but one jurisdiction, the Australian Capital Territory (ACT), had provisions for disclosing identified health information for health research. The ACT's Health Records (Privacy and Access) Act was inconsistent with the other Australian regulation concerning the use of identified health data in health research. The information from the review was used to inform the ACT Government that the health privacy regulations in place were inconsistent with the rest of Australia and resulted in regulatory change in the ACT. ACT legislation was amended to include provisions for the disclosure of identified health information for health research under controlled circumstances. The amendments were passed in December 2005, facilitating future health research involving data linkage in the ACT.


Bonding Durability of a Self-etch Adhesive to Normal Versus Smear-layer Deproteinized Dentin: Effect of a Reducing Agent and Plant-extract Antioxidant.
To evaluate the effect of a reducing agent and plant-extract antioxidant on the bonding durability of a self-etch adhesive to normal and NaOCl-treated, smear-layer-deproteinized dentin. Flat smear-layer-covered dentin surfaces from 60 extracted human molars were prepared by removing the occlusal enamel. The teeth were divided into two groups with or without NaOCl-deproteinizing treatment for 30 s, and further divided into three subgroups as follows: no application of antioxidant, application of Accel (p-toluenesulfinic acid sodium salt solution) for 5 s, or application of rosmarinic acid solution for 5 s. All treated dentin surfaces were bonded with a two-step self-etch adhesive (Clearfil SE Bond) and restored with composite (Clearfil AP-X). The bonded teeth were sectioned into a hourglass-shaped sticks with a composite-dentin bonded interface area of 1.0 mm2. After storage in artificial saliva for 24 h or 1 year, the specimens were subjected to the microtensile bond strength test (n = 15). Data were statistically analyzed with three-way ANOVA, Tukey's post-hoc test, and the t-test (p < 0.05). Without an antioxidant, 1-year storage significantly reduced the bond strengths of the self-etch adhesive to normal and smear-layer-deproteinized dentin compared with those after 24-h storage (p < 0.05). Application of Accel and rosmarinic acid restored the compromised initial bond strengths to smear-layer-deproteinized dentin (p < 0.05), and prevented long-term deterioration of bond strengths to both normal and smear-layer-deproteinized dentin (p > 0.05). Application of Accel and rosmarinic acid improved bonding durability of the self-etch adhesive to both normal and smear-layer-deproteinized dentin.


Does high knee flexion cause separation of meniscal repairs?
Previous clinical studies comparing nonrestrictive and restrictive protocols after meniscal repair have shown no difference in outcomes; however, some surgeons still limit range of motion out of concern that it will place undue stress on the repair. Large acute medial meniscal tears will gap during simulated open chain exercises at high flexion angles, and a repaired construct with vertical mattress sutures will not gap. Controlled laboratory study. Tantalum beads were implanted in the medial menisci of 6 fresh-frozen cadaveric knees via an open posteromedial approach. Each knee underwent 10 simulated open chain flexion cycles with loading of the quadriceps and hamstrings. Testing was performed on 3 different states of the meniscus: intact, torn, and repaired. Biplanar radiographs were taken of the loaded knee in 90°, 110°, and 135° of flexion for each state. A 2.5-cm tear was created in the posteromedial meniscus and repaired with inside-out vertical mattress sutures. Displacement of pairs of beads spanning the tear was measured in all planes by use of radiostereometric analysis (RSA) with an accuracy of better than 80 μm. With a longitudinal tear, compression rather than gapping occurred in all 3 regions of the posterior horn of the meniscus (mean ± standard deviation for medial collateral ligament [MCL], -321 ± 320 μm; midposterior, -487 ± 256 μm; root, -318 ± 150 μm) with knee flexion. After repair, meniscal displacement returned part way to intact values in both the MCL (+55 ± 250 μm) and root region (-170 ± 123 μm) but not the midposterior region, where further compression was seen (-661 ± 278 μm). Acute posteromedial meniscal tears and repairs with vertical mattress sutures do not gap, but rather compress in the transverse plane at higher flexion angles when subjected to physiologic loads consistent with active, open kinetic chain range of motion rehabilitation exercises. The kinematics of the repaired meniscus more closely resemble that of the intact meniscus than that of the torn meniscus in regions adjacent to the MCL and the root but not in the midposterior region, where meniscal repair led to increased compression across the tear plane. This study supports the idea that nonrestrictive unresisted open chain range of motion protocols do not place undue stress on meniscal repairs.


The idea of ageing: an historical and psychological analysis.
The idea of ageing can be traced back to the earliest written records. Prescientific beliefs were governed by animistic forms of thought leading to attempts to control ageing, disease and death through magic and supernatural agencies. The idea of ageing was gradually elaborated in Greek and Roman medicine and incorporated into religious beliefs and social practices. Ideas from the classical period were revived during the Renaissance, but modern scientific approaches to ageing did not emerge clearly until the 17th century, with systematic medical and statistical inquiries into the causes of death, and later, in the 19th and 20th centuries, into the biological mechanisms of ageing. The idea of an 'elixir of life' has been all but totally abandoned, although increases in the average length of life are expected to continue for some time. Refinements in the idea take account of the social and behavioural aspects of ageing.


[Regulation of Na+-K+-ATPase: effect of Mg and Ca ions].
The participation of Mg2+ and Ca2+ in complicated mechanisms of Na+, K(+)-ATPase regulation is discussed in the survey. The regulatory actions of Mg2+ on Na+, K(+)-ATPase such as its participation in phosphorylation and dephosphorylation of the enzyme, ADP/ATP-exchange inhibition, cardiac glycosides and vanadate binding with the enzyme, conformational changes induction during ATPase cycle are reviewed in detail. Some current views of mechanisms of above mentioned Mg2+ regulatory effects are discussed. The experimental evidence of Ca2+ immediate influence on the functional activity of Na+, K(+)-ATPase (catalytic, transport and glycoside-binding) are given. It's noted that these effects are based on the conformational changes in the enzyme and also on the phase transition in membrane induced by Ca2+. Unimmediate action of Ca2+ on Na+, K(+)-ATPase is also discussed, especially due to its effect on other membrane systems functionally linked with Na(+)-pump (for instance, due to Na+/Ca(+)-exchanger activation). It's concluded that Mg2+ and Ca2+ as "universal regulators" of the cell effectively influence the functional activity and conformational states of Na+, K(+)-ATPase.


Effects of visual fatigue caused by smartphones on balance function in healthy adults.
[Purpose] The purpose of this study was to determine the effects of visual fatigue caused by smartphone use on balance function. [Subjects and Methods] The participants consisted of 22 healthy male and female adults. Their postural stability, limit of stability, and limit of stability running time were evaluated using a computerized posturography apparatus before and after inducing visual fatigue. Postural stability and the limit of stability were divided into static and dynamic conditions. [Results] There were significant differences between the dynamic postural stability, the static and dynamic limit of stability, and both the static and dynamic limit of stability running times after the induction of visual fatigue. [Conclusion] The results showed that visual fatigue caused by smartphone use has a negative effect on balance function. Therefore, reducing visual fatigue through proper rest is necessary.


Opposing effects of prostaglandin E2 receptors EP3 and EP4 on mouse and human β-cell survival and proliferation.
Hyperglycemia and systemic inflammation, hallmarks of Type 2 Diabetes (T2D), can induce the production of the inflammatory signaling molecule Prostaglandin E2 (PGE2) in islets. The effects of PGE2 are mediated by its four receptors, E-Prostanoid Receptors 1-4 (EP1-4). EP3 and EP4 play opposing roles in many cell types due to signaling through different G proteins, Gi and GS, respectively. We previously found that EP3 and EP4 expression are reciprocally regulated by activation of the FoxM1 transcription factor, which promotes β-cell proliferation and survival. Our goal was to determine if EP3 and EP4 regulate β-cell proliferation and survival and, if so, to elucidate the downstream signaling mechanisms. β-cell proliferation was assessed in mouse and human islets ex vivo treated with selective agonists and antagonists for EP3 (sulprostone and DG-041, respectively) and EP4 (CAY10598 and L-161,982, respectively). β-cell survival was measured in mouse and human islets treated with the EP3- and EP4-selective ligands in conjunction with a cytokine cocktail to induce cell death. Changes in gene expression and protein phosphorylation were analyzed in response to modulation of EP3 and EP4 activity in mouse islets. Blockade of EP3 enhanced β-cell proliferation in young, but not old, mouse islets in part through phospholipase C (PLC)-γ1 activity. Blocking EP3 also increased human β-cell proliferation. EP4 modulation had no effect on ex vivo proliferation alone. However, blockade of EP3 in combination with activation of EP4 enhanced human, but not mouse, β-cell proliferation. In both mouse and human islets, EP3 blockade or EP4 activation enhanced β-cell survival in the presence of cytokines. EP4 acts in a protein kinase A (PKA)-dependent manner to increase mouse β-cell survival. In addition, the positive effects of FoxM1 activation on β-cell survival are inhibited by EP3 and dependent on EP4 signaling. Our results identify EP3 and EP4 as novel regulators of β-cell proliferation and survival in mouse and human islets ex vivo.


Lamb-type waves generated by a cylindrical bubble oscillating between two planar elastic walls.
The volume oscillation of a cylindrical bubble in a microfluidic channel with planar elastic walls is studied. Analytical solutions are found for the bulk scattered wave propagating in the fluid gap and the surface waves of Lamb-type propagating at the fluid-solid interfaces. This type of surface wave has not yet been described theoretically. A dispersion equation for the Lamb-type waves is derived, which allows one to evaluate the wave speed for different values of the channel height h. It is shown that for h<λt, where λt is the wavelength of the transverse wave in the walls, the speed of the Lamb-type waves decreases with decreasing h, while for h on the order of or greater than λt, their speed tends to the Scholte wave speed. The solutions for the wave fields in the elastic walls and in the fluid are derived using the Hankel transforms. Numerical simulations are carried out to study the effect of the surface waves on the dynamics of a bubble confined between two elastic walls. It is shown that its resonance frequency can be up to 50% higher than the resonance frequency of a similar bubble confined between two rigid walls.


Rollable Microfluidic Systems with Microscale Bending Radius and Tuning of Device Function with Reconfigurable 3D Channel Geometry.
Flexible microfluidic system is an essential component of wearable biosensors to handle body fluids. A parylene-based, thin-film microfluidic system is developed to achieve flexible microfluidics with microscale bending radius. A new molding and bonding technique is developed for parylene microchannel fabrication. Bonding with nanoadhesive layers deposited by initiated chemical vapor deposition (iCVD) enables the construction of microfluidic channels with short fabrication time and high bonding strength. The high mechanical strength of parylene allows less channel deformation from the internal pressure for the thin-film parylene channel than bulk PDMS channel. At the same time, negligible channel sagging or collapse is observed during channel bending down to a few hundreds of micrometers due to stress relaxation by prestretch structure. The flexible parylene channels are also developed into a rollable microfluidic system. In a rollable microfluidics format, 2D parylene channels can be rolled around a capillary tubing working as inlets to minimize the device footprint. In addition, we show that creating reconfigurable 3D channel geometry with microscale bending radius can lead to tunable device function: tunable Dean-flow mixer is demonstrated using reconfigurable microscale 3D curved channel. Flexible parylene microfluidics with microscale bending radius is expected to provide an important breakthrough for many fields including wearable biosensors and tunable 3D microfluidics.


Oxidation-induced C-H amination leads to a new avenue to build C-N bonds.
In this work, we develop an oxidation-induced C-H functionalization strategy, which not only leads to a new avenue to build C-N bonds, but also leads to different site-selectivity compared with "classic directing-groups". The high selectivity of our new catalytic system originates from the heterogeneous electron-density distribution of the radical cation species which are induced by single electron transfer between the aromatics and oxidant-Cu(ii) species.


Oncolytic adenovirus-expressed RNA interference of O6-methylguanine DNA methyltransferase activity may enhance the antitumor effects of temozolomide.
Temozolomide (TMZ) is an example of an alkylating agent, which are known to be effective anticancer drugs for the treatment of various solid tumors, including glioma and melanoma. TMZ acts predominantly through the mutagenic product O6-methylguanine, a cytotoxic DNA lesion. The DNA repair enzyme, O6-methylguanine DNA methyltransferase (MGMT), which functions in the resistance of cancers to TMZ, can repair this damage. RNA interference (RNAi) has been previously shown to be a potent tool for the knockdown of genes, and has potential for use in cancer treatment. Oncolytic adenoviruses not only have the ability to destroy cancer cells, but may also be possible vectors for the expression of therapeutic genes. We therefore hypothesized that the oncolytic virus-mediated RNAi of MGMT activity may enhance the antitumor effect of TMZ and provide a promising method for cancer therapy.


[Ethnic disparity in stillbirth in Denmark--secondary publication].
The purpose of this study was to investigate ethnic disparity in stillbirth, infant mortality and cause-specific infant mortality in Denmark during 1981-2003. From population-covering registries, births from the five largest ethnic minority groups and the Danish majority were identified. Mortality rates and relative risks were calculated for stillbirth and infant mortality. Some ethnic minority groups had increased mortality when compared to majority population. Socioeconomic position did not seem to explain the difference.


Advances of medical nanorobots for future cancer treatments.
Early detection and diagnosis of many cancers is very challenging. Late stage detection of a cancer always leads to high mortality rates. It is imperative to develop novel and more sensitive and effective diagnosis and therapeutic methods for cancer treatments. The development of new cancer treatments has become a crucial aspect of medical advancements. Nanobots, as one of the most promising applications of nanomedicines, are at the forefront of multidisciplinary research. With the progress of nanotechnology, nanobots enable the assembly and deployment of functional molecular/nanosized machines and are increasingly being utilized in cancer diagnosis and therapeutic treatment. In recent years, various practical applications of nanobots for cancer treatments have transitioned from theory to practice, from in vitro experiments to in vivo applications. In this paper, we review and analyze the recent advancements of nanobots in cancer treatments, with a particular emphasis on their key fundamental features and their applications in drug delivery, tumor sensing and diagnosis, targeted therapy, minimally invasive surgery, and other comprehensive treatments. At the same time, we discuss the challenges and the potential research opportunities for nanobots in revolutionizing cancer treatments. In the future, medical nanobots are expected to become more sophisticated and capable of performing multiple medical functions and tasks, ultimately becoming true nanosubmarines in the bloodstream.


Regulation of fetuin A gene expression in the neonatal pig liver.
Fetuin A (also known as α2-Heremans-Schmid glycoprotein) is a protein primarily expressed by the liver and secreted into the blood. Previous studies have suggested that plasma concentrations of fetuin A are elevated with impaired growth rate in swine. The present study was designed to examine the relationship of porcine fetuin A with growth rate in the pig and to also elucidate the regulation of fetuin A expression by examining the hormonal and cytokine regulation of fetuin A mRNA abundance in hepatocytes prepared from suckling piglets. Quantitative real-time PCR assay was used to quantify the number of fetuin A mRNA molecules/molecule cyclophilin mRNA. Total RNA was isolated from liver of three different groups of pigs to assess changes in mRNA abundance of fetuin A: normal piglets at day 1, day 7 day 21 or 6 months of age (n=6 for each age); runt and control piglets at day 1 of age (n=4); slow growing and normal growing piglets at 21 days of age (n=8). Following birth, fetuin A gene expression increased from day 1 and 7 of age (P<0.05), and then declined at 21 days of age (P<0.05), with a much greater decline to 6 months of age (P<0.01). Fetuin A mRNA abundance was higher in runt pigs v. their normal birth weight littermates (P<0.05). Similarly, fetuin A gene expression was higher in livers of pigs that were born at a normal weight but that grew much slower than littermates with the same birth weight (P<0.05). Hepatocytes were isolated from preweaned piglets and maintained in serum-free monolayer culture for up to 72 h to permit examination of the influences of hormones, cytokines and redox modifiers on fetuin A mRNA abundance. Fetuin A gene expression was enhanced by glucagon, T3 and resveratrol (P<0.05). Growth hormone, cytokines (interleukin6, tumor necrosis factor-α) and antioxidants (N-acetylcysteine, quercertin) reduced fetuin A mRNA abundance (P<0.05). A role for fetuin A in postnatal development is suggested by the differences in fetuin A mRNA abundance between runt piglets or slow growing piglets and their normal growing sized littermates. The hepatocyte experiments suggest multiple hormones and cytokines may contribute to the regulation of fetuin A during early growth of the pig.


Relative risk of adolescent drug abuse: Part II. Intrapsychic variables.
The total sample size for the study of intrapsychic variables was 252 (152 non-drug users and 100 life-time users including 69 current users). Using a multiphasic personality questionnaire, the Eysenck personality inventory and an orientation questionnaire, the authors found that high orientation, extraversion, anxiety and psychopathic deviate scores were associated with a relative risk of drug use. No significant difference is reported between the mean scores of users and non-users on mania, paranoia, depression, schizophrenia, hysteria and neuroticism.


Inclusion of chloromethane guests affects conformation and internal dynamics of cryptophane-D host.
Cryptophane-D is composed of two nonequivalent cyclotribenzylene caps bound together by three OCH2CH2O bridges in a syn arrangement. Host-guest complexes with chloroform and dichloromethane were investigated in solution by NMR spectroscopy. Variable temperature NMR (1)H and (13)C spectra showed effects of chemical exchange between the free and bound guest and of conformational exchange for the host, strongly and specifically affected by guest binding. We found in particular that the carbon-13 chemical shifts for the linkers connecting the two cyclotribenzylene units are very informative. The NMR results were supported by DFT calculations. The guest exchange was also studied quantitatively, either by EXSY measurements (for chloroform as guest) or by line-shape analysis (for dichloromethane as guest). In the case of chloroform guest, we also investigated cross-relaxation between the guest and host protons, as well as carbon-13 longitudinal relaxation and heteronuclear NOE at three different fields. The results were interpreted in terms of orientation and dynamics of the guest inside the host cavity. Putting together various types of evidence resulted in remarkably detailed insight into the process of molecular recognition of the two guests by cryptophane-D host.


A Fusion Method for Combining Low-Cost IMU/Magnetometer Outputs for Use in Applications on Mobile Devices.
This paper presents a fusion method for combining outputs acquired by low-cost inertial measurement units and electronic magnetic compasses. Specifically, measurements of inertial accelerometer and gyroscope sensors are combined with no-inertial magnetometer sensor measurements to provide the optimal three-dimensional (3D) orientation of the sensors' axis systems in real time. The method combines Euler⁻Cardan angles and rotation matrix for attitude and heading representation estimation and deals with the "gimbal lock" problem. The mathematical formulation of the method is based on Kalman filter and takes into account the computational cost required for operation on mobile devices as well as the characteristics of the low-cost microelectromechanical sensors. The method was implemented, debugged, and evaluated in a desktop software utility by using a low-cost sensor system, and it was tested in an augmented reality application on an Android mobile device, while its efficiency was evaluated experimentally.


Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia.
We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.


Biosafety considerations for autopsy.
An autopsy may subject prosectors and others to a wide variety of infectious agents, including bloodborne and aerosolized pathogens such as human immunodeficiency virus, hepatitis B and C viruses, and Mycobacterium tuberculosis. Other hazards include toxic chemicals (e.g., formalin, cyanide, and organophosphates) and radiation from radionuclides used for patient therapy and diagnosis. These risks can be substantially mitigated through proper assessment, personal protective equipment, appropriate autopsy procedures, and facility design.


Aerial image based technique for measurement of lens aberrations up to 37th Zernike coefficient in lithographic tools under partial coherent illumination.
This paper proposes a technique for in situ measurement of lens aberrations up to the 37th Zernike coefficient in lithographic tools under partial coherent illumination. The technique requires the acquisition and analysis of aerial image intensities of a set of 36 binary gratings with different pitches and orientations. By simplifying the theoretical derivation of the optical imaging under partial coherent illumination, two linear models are proposed in a compact expression with two matrixes, which can be easily obtained in advance by numerical calculation instead of by lithographic simulators, and then used to determine the Zernike coefficients of odd aberration and even aberration respectively. The simulation work conducted by PROLITH has validated the theoretical derivation and confirms that such a technique yields a superior quality of wavefront estimate with an accuracy of Zernike coefficients on the order of 0.1 m lambdas (lambda = 193 nm) and an accuracy of wavefronts on the order of m lambdas, due to further considering the influence of the partial coherence factor on pupil sampling. It is fully expected that this technique will simple to implement and will provide a useful practical means for the in-line monitoring of imaging quality of lithographic tools under partial coherent illumination.


[Prognostic significance of acute bundle branch block in patients with acute myocardial infarction].
Acute bundle branch block (ABBB) presence is associated with the increasing mortality of patients with acute myocardial infarction (AMI). The aim of this study was investigate ABBB influence with respect to in-hospital (IN) and long-term mortality in patients with AIM, as well as total mortality in follow-up, the presence of in-hospital congestive cardiac insufficiency (CCI) and the presence of CCI at follow-up. This study included 606 consecutive patients with AMI. A total of 415 (68.5%) were males and 191 (31.5%) females, mean age 64.0 +/- 11.9. After the dismissal the patients underwent 18-month follow-up period. Acute bundle branch block was registered in 44 patients (7.2%), out of which 15 patients (2.4%) had the left (L) ABBB and 29 patients (4.8%) had the right (R) ABBB. The patients with ABBB showed higher proportion of IH CCI (Killip III and IV) and hypotension compared with the control group (patients without ABBB). In the group of patients with ABBB beta-blockers, statins, aspirin and ACE-inhibitors were less applied. All the three ABBB groups exhibited an increased IH mortality (ABBB 47.7% vs 11.2%, p < 0.01, ARBBB 55.1% vs 11.2% p < 0.01, ALBBB 33.3% vs 11.2%, p < 0.01). Follow-up mortality of the patients with ABBB and ALBBB was higher in comparison with the control group (log-rank p = 0.046 and log-rank p = 0.01, respectively), whereas the group with ARBBB did not show any differences (log-rank, p = 0.59). The patients with ABBB AMI are a risk group of patients that commonly exhibit both early and remote CCI accompanied by high mortality. That is the reason why this sub-group of AMI patients should receive an urgent diagnostics followed by aggressive therapeutic treatment.


Focal lymphocytic infiltration in the human labial salivary glands: a postmortem study.
Focal lymphocytic infiltration in the human labial salivary glands was examined in a series of 190 postmortem subjects after suitable exclusion had been made. Focal lymphocytic infiltration, with or without a slight degree of parenchymal atrophic change, was found in 22.4% of the males and in 35.7% of the females. Of these, 9.0% (12 subjects) of the males and 10.7% (6 subjects) of the females with focal lymphocytic infiltration did not show any atrophic changes of the parenchyma. In the series reported here, the prevalence of focal lymphocytic infiltration apparently differs from the results of earlier investigators who had reported that none of the postmortem subjects without autoimmune diseases or connective tissue diseases showed focal lymphocytic infiltration in minor salivary glands. Although the pathological significance of focal lymphocytic infiltration in the minor salivary glands remains obscure, its diagnostic value for Sjögren's syndrome is discussed.


Knowledge of Infant Development and Parent Well-Being: Cross-Sectional Analysis of Toddlers.
Knowledge about child development is associated with parenting and children's outcomes. Parents with less accurate knowledge about developmental milestones may have unrealistic expectations for their child's behavior, which may affect parent well-being. Limited research has examined this topic relative to depression, but other aspects of parent well-being (e.g., parenting stress) are unexplored. Cross-sectional analysis of an ongoing prospective cohort study of 300 families in central Ohio enrolled when children were a mean (SD) calendar age of 18.2 (0.7) months. Children of all gestational ages at birth are included, and 37% were born preterm (<37 weeks' gestation.) Primary caregivers (93% mothers) completed the 20-item Knowledge of Infant Development Index (KIDI) and questionnaires for child temperament and 3 aspects of parent well-being (depressive and anxious symptoms, parenting stress, and general health). Covariate-adjusted regression models assessed relationships between the KIDI score and each well-being outcome. We hypothesized that parents with less knowledge would have more symptoms of depression and anxiety, greater parenting stress, and poorer health. Whether associations were stronger for parents of children born preterm or who had high negative affect was explored. Knowledge of Infant Development Index scores were associated with sociodemographic characteristics, child temperament, and gestational age (more knowledge: higher socioeconomic position, less child negative affect, and full-term birth). KIDI scores did not predict any aspect of parent well-being, and there was no evidence that child temperament or preterm birth altered these findings. In this sample of parents of toddlers assessed in 2018/19, greater knowledge of infant development was not associated with parent well-being.


Impact of the antibiotic doxycycline on the D. magna reproduction, associated microbiome and antibiotic resistance genes in treated wastewater conditions.
Wastewater Treatment Plant (WWTP) effluents are important sources of antibiotics, antibiotic resistance genes (ARGs) and resistant bacteria that threaten aquatic biota and human heath. Antibiotic effects on host-associated microbiomes, spread of ARGs and the consequences for host health are still poorly described. This study investigated changes of the Daphnia magna associated microbiome exposed to the recalcitrant antibiotic doxycycline under artificial reconstituted lab water media (lab water) and treated wastewater media. D. magna individual juveniles were exposed for 10 days to treated wastewater with and without doxycycline, and similarly in lab water. We analysed 16 S rRNA gene sequences to assess changes in community structure, monitored Daphnia offspring production and quantified ARGs abundances by qPCR from both Daphnia and water (before and after the exposure). Results showed that doxycycline and media (lab water or wastewater) had a significant effect modulating Daphnia-associated microbiome composition and one of the most discriminant taxa was Enterococcus spp. Moreover, in lab water, doxycycline reduced the presence of Limnohabitans sp., which are dominant bacteria of the D. magna-associated microbiome and impaired Daphnia reproduction. Contrarily, treated wastewater increased diversity and richness of Daphnia-associated microbiome and promoted fecundity. In addition, the detected ARG genes in both lab water and treated wastewater medium included the qnrS1, sul1, and blaTEM, and the integron-related intI1 gene. The treated wastewater contained about 10 times more ARGs than lab water alone. Furthermore, there was an increase of sul1 in Daphnia cultured in treated wastewater compared to lab water. In addition, there were signs of a higher biodegradation of doxycycline by microbiomes of treated wastewater in comparison to lab water. Thus, results suggest that Daphnia-associated microbiomes are influenced by their environment, and that bacterial communities present in treated wastewater are better suited to cope with the effects of antibiotics.


Setting up computed tomography automatic tube current modulation systems.
Automatic tube current modulation (ATCM) on CT scanners can yield significant reductions in patient doses. Modulation is based on x-ray beam attenuation in body tissues obtained from scan projection radiographs (SPRs) and aims to maintain the same level of image quality throughout a scan. Noise level is important in judging image quality, but tissues in larger patients exhibit higher contrast resulting from the presence of fat. CT scanner manufacturers use different metrics to assess image quality. Some employ a simple measure of image noise, while others adopt a measure related to a reference image that accepts higher noise levels in more attenuating parts with higher contrast. At the present time there is no standard method for testing ATCM. This paper reviews the operation of different ATCM systems, considers options for testing, and sets out a framework that could be used for optimizing clinical protocols. If dose and image quality can be established for a reference phantom, the modulation performed by ATCM systems can be characterised using anatomical phantoms or geometrical elliptical phantoms which may be conical or include sections of varying dimension. For scanners using a reference image or mAs, selection of the image quality reference determines other factors. However, for scanners using a noise reference, a higher noise level should be selected for larger patients to avoid high doses, and the operator should ensure that appropriate limits are set for mA modulation. Other factors that need to be considered include the SPRs used to plan the ATCM and image thickness. Users should be aware of the mode of operation of the ATCM system on their CT scanner, and be familiar with the effects of changing different protocol parameters. The behaviour of ATCM systems should be established through testing of each CT scanner with suitable phantoms during commissioning.


NMR Methods to Study the Dynamics of SH2 Domain-Phosphopeptide Complexes.
Nuclear magnetic resonance (NMR) spectroscopy is the method of choice for studying the dynamics of biological macromolecules in solution. By exploiting the intricate interplay between the effects of protein motion (both overall rotational diffusion and internal mobility) and nuclear spin relaxation, NMR allows molecular motion to be probed at atomic resolution over a wide range of timescales, including picosecond (bond vibrations and methyl-group rotations), nanosecond (loop motions and rotational diffusion), and microsecond-millisecond (ligand binding, allostery). In this chapter, we describe different NMR pulse schemes (R1, R1ρ, heteronuclear NOE, and CPMG relaxation dispersion) to characterize the dynamics of SH2 domains. As an example, we use the N-SH2 domain of protein tyrosine phosphatase SHP2 in complex with two phosphopeptides derived from immune checkpoint receptor PD-1 (ITIM and ITSM).


Gerrymandering for Justice: Redistricting U.S. Liver Allocation.
U.S. organ allocation policy sequesters livers from deceased donors within arbitrary geographic boundaries, frustrating the intent of those who wish to offer the livers to transplant candidates based on medical urgency. We used a zero-one integer program to partition 58 donor service areas into between four and eight sharing districts that minimize the disparity in liver availability among districts. Because the integer program necessarily suppressed clinically significant differences among patients and organs, we tested the optimized district maps with a discrete-event simulation tool that represents liver allocation at a per-person, per-organ level of detail. In April 2014, the liver committee of the Organ Procurement and Transplantation Network (OPTN) decided in a unanimous vote of 22-0-0 to write a policy proposal based on our eight-district and four-district maps. The OPTN board of directors could implement the policy after the proposal and public-comment period.Redistricting liver allocation would save hundreds of lives over the next five years and would attenuate the serious geographic inequity in liver transplant offers.


It's Time to Go Quantum in Medicine.
As the field of medicine grows and expands, new scientific developments hold great promise for improving quality of care, clinical research, and the diagnosis and treatment of diseases. Quantum physics is a promising field that intersects with medicine much more than originally understood. In terms of diagnosing different diseases, incorporating quantum mechanics into the study of medicine can allow for efficient diagnosis before symptoms even arise in a patient. Applying theory-based mathematical structures that describe neuron transmission throughout the brain and mind on a quantum scale can help us to better understand neurological diseases in patients. Quantum theory can even give plausible explanations for subtle DNA changes and even telomere reduction in patients who develop cancer. Utilizing quantum theory in the field of medicine can help in understanding and applying treatments for a multitude of different diseases, such as Alzheimer's disease or diverse types of cancer, and even expand upon efficient and reliable diagnosis in clinical settings. Quantum physics is a pertinent advancing field that may have a significant impact on expanding medical care and treatment in the near future. In this review, the application of quantum physics in medicine is discussed.


Dialkoxybithiazole: a new building block for head-to-head polymer semiconductors.
Polymer semiconductors have received great attention for organic electronics due to the low fabrication cost offered by solution-based printing techniques. To enable the desired solubility/processability and carrier mobility, polymers are functionalized with hydrocarbon chains by strategically manipulating the alkylation patterns. Note that head-to-head (HH) linkages have traditionally been avoided because the induced backbone torsion leads to poor π-π overlap and amorphous film microstructures, and hence to low carrier mobilities. We report here the synthesis of a new building block for HH linkages, 4,4'-dialkoxy-5,5'-bithiazole (BTzOR), and its incorporation into polymers for high performance organic thin-film transistors. The small oxygen van der Waals radius and intramolecular S(thiazolyl)···O(alkoxy) attraction promote HH macromolecular architectures with extensive π-conjugation, low bandgaps (1.40-1.63 eV), and high crystallinity. In comparison to previously reported 3,3'-dialkoxy-2,2'-bithiophene (BTOR), BTzOR is a promising building block in view of thiazole geometric and electronic properties: (a) replacing (thiophene)C-H with (thiazole)N reduces steric encumbrance in -BTzOR-Ar- dyads by eliminating repulsive C-H···H-C interactions with neighboring arene units, thereby enhancing π-π overlap and film crystallinity; and (b) thiazole electron-deficiency compensates alkoxy electron-donating characteristics, thereby lowering the BTzOR polymer HOMO versus that of the BTOR analogues. Thus, the new BTzOR polymers show substantial hole mobilities (0.06-0.25 cm(2)/(V s)) in organic thin-film transistors, as well as enhanced I(on):I(off) ratios and greater ambient stability than the BTOR analogues. These geometric and electronic properties make BTzOR a promising building block for new classes of polymer semiconductors, and the synthetic route to BTzOR reported here should be adaptable to many other bithiazole-based building blocks.


Comparison between single- and double-bundle anterior cruciate ligament reconstructions for knee with grade 2 medial collateral ligament injury.
This research discussed clinical outcomes of anterior cruciate ligament reconstruction accompanied by conservative treatment for grade 2 medial collateral ligament injury, and comparison was performed between double-bundle and single-bundle anterior cruciate ligament reconstruction.Clinical information was retrospectively collected for 41 cases suffering anterior cruciate ligament injuries accompanied by grade 2 medial collateral ligament injuries. Within 14 days after their injuries 22 cases received single-bundle anterior cruciate ligament reconstruction (SB group), while 19 were treated with double-bundle medial collateral ligament reconstruction (DB group). Physical statuses were estimated based on International Knee Documentation Committee (IKDC) and Lysholm scores, Lachman, pivot shift and manual valgus test, and range of motion (ROM), while side-to-side difference was estimated through KT 2000 arthometer.Anterior cruciate ligament reconstruction accompanied by conservative treatment showed significantly improved anteroposterior, rotational and valgus stability, and IKDC and Lysholm scores (in comparison to pre-operative status, P < .05). Incidence of pivot shift was dramatically lower in DB group (2/19) than in SB group (7/22 and 2/22; P = .028). No substantial dissimilarity existed between DB and SB groups either in Lachman and valgus tests, KT 2000, ROM, IKDC, or Lysholm scores.Anterior cruciate ligament reconstruction accompanied by conservative treatment could achieve outstanding stability and functional manifestations for cases facing anterior cruciate ligament injury accompanied by grade 2 medial collateral ligament injury. Moreover, double-bundle anterior cruciate ligament reconstruction is superior to single-bundle operation in treating rotational instability of the knee.Level of evidence: Retrospective comparative study, Level III.


Management of Ankle Fractures With Syndesmotic Disruption: A Survey of Orthopaedic Surgeons.
With no current "gold standard" fixation strategy for syndesmotic injuries and differences in preferred preoperative and intraoperative diagnostic techniques and criteria, methods of reduction, fixation constructs, and postoperative management, the goals of this study were to determine how orthopaedic surgeons currently manage ankle fractures with concomitant syndesmotic disruption, as well as to identify surgeon demographics predictive of syndesmotic management techniques. This study was conducted as a web-based survey of foot and ankle fellowship-trained surgeons, Orthopaedic Trauma Association (OTA) members, and Canadian Orthopaedic Association (COA) members. The survey, sent and completed via the HIPAA-compliant Research Electronic Data Capture (REDCap) system, consisted of 18 questions: 6 surgeon demographic questions and 12 specific syndesmotic management questions regarding perioperative protocols and syndesmotic fixation construct techniques. One hundred and ten orthopaedic surgeons completed our survey. Years of practice and type of fellowship were found to be the variables that influenced perioperative syndesmotic management strategies the most, while a number of fractures operated on per year, country of practice, and practice setting also influenced management decisions. Additionally, 59% (65/110) surgeons indicated that the way they have managed syndesmotic injuries has changed at some point in their career, while 33% (36/110) specified that they could foresee themselves changing their management of these injuries in the future. There was significant variability among responders in preoperative and intraoperative assessment technique, fixation construct, screw removal protocol, and postoperative weightbearing protocol. This study raises awareness of differences in and factors predictive of management strategies and should be used for further discussion when determining a potential gold standard for the management of these complex injuries.


Effectiveness And Acceptability Of Ready-To-Use Therapuetic Foods Among Malnourished Children In A Tertiary Care Hospital.
Ready-to-use-therapeutic foods (RUTF) are an important component of the effective outpatient treatment of severe wasting because most of the child deaths in the world especially in developing countries is due to malnutrition. The objective of the study was to evaluate the effectiveness and acceptability of ready to use therapeutic food among malnourished children in a tertiary care hospital. An observational exploratory study based on sixty subjects with 3-120 months of age, malnourished children were chosen by universal sampling from Children Hospital Lahore, Pakistan, during the time period 1st September 2012 to 30th November 2012 with the approval of ethical committee. The study tool for investigation was a well-structured questionnaire. The highest proportion of malnourished children belonged to urban areas (71.67%) and age group <24 months (65%).The effect of RUTF on weight for height and weight for age Z score from baseline to the end of follow-up was statistically significant (Paired sample t-test) (p=0.000, 0.000) but there was no significant effect of RUTF on height for age (p-value=0.14).The acceptance of food among patients was good, the proportion of patient was higher who consumed ready to use therapeutic food easily (70%), percentage of vomiting (16.7%) and complaints of diarrhoea (46.7%) after taking RUTF was less in patients. All mothers were satisfied from ready to use therapeutic foods (100%). Malnourished children gained weight after the short term supplementation of ready to use therapeutic food but had no significant effect on height of the patients. Its acceptability in term of taste, amount consumes and demand was good. Mother's perception was also satisfactory regarding these foods.


Ionization of liquids by radiation: measurement by a clearing field.
A method has been developed for determining the yield of free ions formed by irradiation of a liquid with high-energy x-rays. Contrary to expectation, branched-chain paraffins produce many more free ions than straight-chain paraffins do, and the ether 1,4-dioxane produced only a third as many free ions as its hydrocarbon analog, cyclohexane.


His-311 and Arg-559 are key residues involved in fatty acid oxygenation in pathogen-inducible oxygenase.
Pathogen-inducible oxygenase (PIOX) oxygenates fatty acids into 2R-hydroperoxides. PIOX belongs to the fatty acid alpha-dioxygenase family, which exhibits homology to cyclooxygenase enzymes (COX-1 and COX-2). Although these enzymes share common catalytic features, including the use of a tyrosine radical during catalysis, little is known about other residues involved in the dioxygenase reaction of PIOX. We generated a model of linoleic acid (LA) bound to PIOX based on computational sequence alignment and secondary structure predictions with COX-1 and experimental observations that governed the placement of carbon-2 of LA below the catalytic Tyr-379. Examination of the model identified His-311, Arg-558, and Arg-559 as potential molecular determinants of the dioxygenase reaction. Substitutions at His-311 and Arg-559 resulted in mutant constructs that retained virtually no oxygenase activity, whereas substitutions of Arg-558 caused only moderate decreases in activity. Arg-559 mutant constructs exhibited increases of greater than 140-fold in Km, whereas no substantial change in Km was observed for His-311 or Arg-558 mutant constructs. Thermal shift assays used to measure ligand binding affinity show that the binding of LA is significantly reduced in a Y379F/R559A mutant construct compared with that observed for Y379F/R558A construct. Although Oryza sativa PIOX exhibited oxygenase activity against a variety of 14-20-carbon fatty acids, the enzyme did not oxygenate substrates containing modifications at the carboxylate, carbon-1, or carbon-2. Taken together, these data suggest that Arg-559 is required for high affinity binding of substrates to PIOX, whereas His-311 is involved in optimally aligning carbon-2 below Tyr-379 for catalysis.


Functional dynamics of hippocampal glutamate during associative learning assessed with in vivo 1H functional magnetic resonance spectroscopy.
fMRI has provided vibrant characterization of regional and network responses associated with associative learning and memory; however, their relationship to functional neurochemistry is unclear. Here, we introduce a novel application of in vivo proton functional magnetic resonance spectroscopy (1H fMRS) to investigate the dynamics of hippocampal glutamate during paired-associated learning and memory in healthy young adults. We show that the temporal dynamics of glutamate differed significantly during processes of memory consolidation and retrieval. Moreover, learning proficiency was predictive of the temporal dynamics of glutamate such that fast learners were characterized by a significant increase in glutamate levels early in learning, whereas this increase was only observed later in slow learners. The observed functional dynamics of glutamate provides a novel in vivo marker of brain function. Previously demonstrated N-methyl-D-aspartate (NMDA) receptor mediated synaptic plasticity during associative memory formation may be expressed in glutamate dynamics, which the novel application of 1H MRS is sensitive to. The novel application of 1H fMRS can provide highly innovative vistas for characterizing brain function in vivo, with significant implications for studying glutamatergic neurotransmission in health and disorders such as schizophrenia.


Prevalence and Contributing Factors of Childhood Trauma, Anxiety, and Depression Among Adolescents From Two-Child Families in China.
The two-child policy has been implemented in China since 2016 and has attracted the attention of the world. Adolescents may face huge psychological challenges in the process of changing family structures and relationships. To date, no mental health survey of adolescents from two-child families has been conducted. We investigated the prevalence and risk factors for childhood trauma, anxiety, and depression in two-child families in a statistically representative sample of Chinese senior high school students from Shanghai. A total of 426 participants were randomly selected from 1,059 students of four senior high schools in different districts of Shanghai. The childhood trauma questionnaire-short form (CTQ-SF), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used as the screening tools. We found that the overall prevalence of childhood trauma, anxiety, and depression among senior high school students in two-child families was 46.70% (95% CI, 39.93-53.47%), 22.17% (95% CI, 16.53-27.81%), and 35.85% (95% CI, 29.34-42.36%), respectively. The two-child families was an important factor associated childhood trauma, emotional neglect, and physical neglect (χ2 = 5.984, p = 0.014; χ2 = 4.071, p = 0.044; χ2 = 4.202, p = 0.040). Ranking in two-child families was a risk factor for childhood trauma (β = -0.135, p = 0.048). Parental preference was a significantly correlated with physical abuse, physical neglect, anxiety, and depression (β = -1.581 to 0.088, p < 0.05). Meanwhile, emotional abuse, physical abuse, emotional neglect, and physical neglect of participants in the two groups were positively correlated with anxiety and depression (r = 0.195-0.478, p < 0.05). There was a significant relationship between sexual abuse and anxiety symptoms in the one-child family group (r = 0.161, p < 0.05). The findings suggest that the overall prevalence of childhood trauma, anxiety and depression among adolescents from two-child families in China was high. The two-child families and family ranking are important factors associated childhood trauma, while parental preference is related to anxiety and depression. These results highlight an urgent need to be addressed by adolescents' mental health service providers and policy-makers.


Diagnostic efficacy of smear cytology and Robinson's cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival.
Cytology is a simple, rapid, and inexpensive method used for pre-operative diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related to human breast cancer showed the Robinson's grading system-established for invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on cytological material-to not only closely correspond to the histopathological grading but also be helpful in assessing prognosis and selecting most suitable treatments before surgery. The objectives of this study were: to evaluate the accuracy of cytological diagnosis and cytological Robinson's grading system compared to the histopathological examination of CMTs; to compare of cytological features and cytomorphometric parameters with tumor behavior, as well as cytological and histological grading; and to determine an association of the Robinson's grading system and cytological background details with metastases, and patients' survival. We report substantial diagnostic accuracy in detecting simple types and high grade tumors. Cytological diagnosis of tumor behavior showed relatively low sensitivity and specificity compared to human studies, and this might be caused by the heterogeneous morphology of CMTs. The presence of mucosecretory material and extracellular matrix was not significantly associated with tumor behavior. We report a positive correlation between both grading systems and cytological features (included in Robinson's grading), the presence of necrotic debris, inflammation, and red blood cells. A negative correlation was determined only for the presence of extracellular matrix. The univariate and multivariate analyses confirmed a significantly higher risk of developing metastasis and shorter overall survival for dogs with tumors of grade 2 or 3 on cytology. In addition, these tumors were the most common cause of CMT-related deaths in dogs. Taken together, our findings suggest that the Robinson's method of cytological grading applied for malignant CMTs evaluated in cytological smears regardless of tumor type can be adapted to veterinary cytology. Additionally, some background features seem to aid malignancy assessment.


Foxa1-deficient mice exhibit impaired insulin secretion due to uncoupled oxidative phosphorylation.
Foxa1 (formerly hepatic nuclear factor 3alpha) belongs to the family of Foxa genes that are expressed in early development and takes part in the differentiation of endoderm-derived organs and the regulation of glucose homeostasis. Foxa1-/- pups are growth retarded and hypoglycemic but glucose intolerant in response to an intraperitoneal glucose challenge. However, the mechanism of glucose intolerance in this model has not been investigated. Here, we show that Foxa1-/- islets exhibit decreased glucose-stimulated insulin release in islet perifusion experiments and have significantly reduced pancreatic insulin and glucagon content. Moreover, Foxa1-/- beta-cells exhibit attenuated calcium influx in response to glucose and glyburide, suggesting an insulin secretion defect either at the level or upstream of the ATP-sensitive K+ channel. Intracellular ATP levels after incubation with 10 mmol/l glucose were about 2.5 times lower in Foxa1-/- islets compared with controls. This diminished ATP synthesis could be explained by increased expression of the mitochondrial uncoupling protein uncoupling protein 2 (UCP2) in Foxa1-deficient islets, resulting in partially uncoupled mitochondria. Chromatin immunoprecipitation assays indicate that UCP2 is a direct transcriptional target of Foxa1 in vivo. Thus, we have identified a novel function for Foxa1 in the regulation of oxidative phosphorylation in pancreatic beta-cells.


Origin of fecal contamination in waters from contrasted areas: stanols as Microbial Source Tracking markers.
Improving the microbiological quality of coastal and river waters relies on the development of reliable markers that are capable of determining sources of fecal pollution. Recently, a principal component analysis (PCA) method based on six stanol compounds (i.e. 5β-cholestan-3β-ol (coprostanol), 5β-cholestan-3α-ol (epicoprostanol), 24-methyl-5α-cholestan-3β-ol (campestanol), 24-ethyl-5α-cholestan-3β-ol (sitostanol), 24-ethyl-5β-cholestan-3β-ol (24-ethylcoprostanol) and 24-ethyl-5β-cholestan-3α-ol (24-ethylepicoprostanol)) was shown to be suitable for distinguishing between porcine and bovine feces. In this study, we tested if this PCA method, using the above six stanols, could be used as a tool in "Microbial Source Tracking (MST)" methods in water from areas of intensive agriculture where diffuse fecal contamination is often marked by the co-existence of human and animal sources. In particular, well-defined and stable clusters were found in PCA score plots clustering samples of "pure" human, bovine and porcine feces along with runoff and diluted waters in which the source of contamination is known. A good consistency was also observed between the source assignments made by the 6-stanol-based PCA method and the microbial markers for river waters contaminated by fecal matter of unknown origin. More generally, the tests conducted in this study argue for the addition of the PCA method based on six stanols in the MST toolbox to help identify fecal contamination sources. The data presented in this study show that this addition would improve the determination of fecal contamination sources when the contamination levels are low to moderate.


Statin Intolerance and Risk of Coronary Heart Events and All-Cause Mortality Following Myocardial Infarction.
Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality. This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy. We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013. Statin intolerance was defined as down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having International Classification of Diseases, 9th revision, diagnostic codes for rhabdomyolysis or an antihyperlipidemic adverse event, followed by statin down-titration or discontinuation, or switching between ≥3 types of statins within 1 year after initiation. High statin adherence over the year following hospital discharge was defined as proportion of days covered ≥80%. Recurrent MI, CHD events (recurrent MI or a coronary revascularization procedure), and mortality were identified from 1 year after hospital discharge through December 2014. Overall, 1,741 patients (1.65%) had statin intolerance, and 55,567 patients (52.8%) had high statin adherence. Over a median of 1.9 to 2.3 years of follow-up, there were 4,450 recurrent MIs, 6,250 CHD events, and 14,311 deaths. Compared to beneficiaries with high statin adherence, statin intolerance was associated with a 36% higher rate of recurrent MI (41.1 vs. 30.1 per 1,000 person-years, respectively), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years, respectively), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years, respectively). The multivariate-adjusted hazard ratios (HR) comparing beneficiaries with statin intolerance versus those with high statin adherence were 1.50 (95% confidence interval [CI]: 1.30 to 1.73) for recurrent MI, 1.51 (95% CI: 1.34 to 1.70) for CHD events, and 0.96 (95% CI: 0.87 to 1.06) for all-cause mortality. Statin intolerance was associated with an increased risk for recurrent MI and CHD events but not all-cause mortality.


Quantitative mass spectrometry analysis of intact hemoglobin A2 by precursor ion isolation and detection.
Precise and accurate quantification of proteins is essential in clinical laboratories. Here, we present a mass spectrometry (MS)-based method for the quantification of intact proteins in an ion trap mass spectrometer. The developed method is based on the isolation and detection of precursor ions for the quantification of the corresponding signals. The method was applied for the quantification of hemoglobin (Hb) A2, a marker used for the diagnosis of a β-thalassemia trait. The α and δ globin chains, corresponding to total Hb and HbA2, respectively, were isolated in the ion trap at specific charge states and ejected without activation. Areas of the corresponding isolated precursor ions were used to calculate the δ to α ratio. Three series of quantifications were performed on 7 different days. The standard curve fitted linearly (R(2) = 0.9982) and allowed quantification of HbA2 over a concentration range from 3% to 18% of total Hb. Analytical imprecision ranged from 3.5% to 5.3%, which is enough to determine if the HbA2 level is below 3.5% or above 3.7%. In conclusion, our method reaches precision requirements that would be acceptable for the quantitative measurement of diagnostic proteins, such as HbA2, in clinical laboratories.


Evidence for altered DNA conformations in the simian virus 40 genome: site-specific DNA cleavage by the chiral complex lambda-tris(4,7-diphenyl-1,10-phenanthroline)cobalt(III).
lambda-Tris(4,7-diphenyl-1,10-phenanthroline)cobalt(III), a photoactivated DNA-cleaving agent, is a small molecular probe of DNA structure. Because of its chirality, the complex cannot bind to regular right-handed B-form DNA but exhibits site-specific cleavage along the polymer strand at conformationally distinct sites such as those in a left-handed conformation. Both coarse and higher resolution mapping experiments using the chiral cobalt complex indicate intriguing conformational variations along the simian virus 40 genome. Highly specific cleavage is evident in the enhancer and promoter blocks and in the region downstream of 3' termini. A specific cleavage pattern borders an alternating purine/pyrimidine stretch within the enhancer, which was found earlier to bind anti-Z-DNA antibodies. Throughout the simian virus 40 genome, variations in structure delineated with the cobalt complex appear to correlate with regions important for control of gene expression.


Balloon aortic valvuloplasty for severe aortic stenosis as a bridge to high-risk transcatheter aortic valve implantation.
To provide data on feasibility, safety and efficacy of balloon aortic valvuloplasty (BAV) as a bridge to transcatheter aortic valve implantation (TAVI). Background. There are no data on BAV use as a bridge to TAVI in patients at high risk of periprocedural complications. Between June 2007 to May 2009, 83 consecutive patients with symptomatic severe aortic stenosis (48 female, 35 male) aged from 65 to 88 years (mean age 81 +/- 5 years) were treated with TAVI. Early hemodynamic and clinical outcomes of patients undergoing palliative BAV before TAVI (BAV Group, n = 43) were compared with those of patients who directly underwent TAVI (no-BAV Group, n = 40). Patients in the BAV group had worse baseline clinical characteristics than those in the no-BAV group, with higher rates of congestive heart failure, New York Heart Association (NYHA) functional class III or IV and a higher EuroSCORE. In the BAV group, significant changes were found after valvuloplasty with regard to NYHA functional class, mean pressure gradient and aortic valve area. Peak-to-peak transvalvular pressure gradient and left ventricular systolic pressure also decreased immediately after BAV. Before TAVI, no differences in either clinical status or hemodynamic data were observed between patients who underwent BAV and those who did not. Bridging to TAVI with BAV is a feasible and reasonably safe approach to offer temporary relief in selected high-risk patients with symptomatic severe aortic stenosis and a high chance of periprocedural complications.


[2,6-Bis(5-methyl-2-pyridyl)phenyl-kappa(3)N,C(1),N']chloridoplatinum(II).
In the title compound, [Pt(C(18)H(15)N(2))Cl], the Pt(II) centre adopts a distorted square-planar coordination geometry due to the pincer-type monoanionic N-C-N tridentate ligand. The planar complexes stack via pi-pi interactions to form two-dimensional accumulated sheets. This packing pattern is in contrast to that in related pincer-type N-C-N complexes, which exhibit a one-dimensional columnar stacking.


Evaluating the teaching of a method of psychotherapy.
A teaching package was produced to help trainees in psychiatry learn the techniques specific to a 'conversational model' of psychotherapy, prior to group supervision. This consisted of a booklet and three videotapes. The third tape used a micro-counselling approach to illustrate each key skill and was viewed together with a teacher. After this, trainees met in groups of three with a psychotherapist for eight weekly sessions. To evaluate this teaching, 12 trainees were asked to interview simulated patients before and after they used the package and after supervision. These interviews were recorded on videotape and rated. There were significant improvements on most of the key skills as a result of this training, and nine of the 12 trainees improved considerably. There was a strong negative correlation between improvement scores and a biological orientation to psychiatry. It is concluded that the teaching package is an economic but effective way of helping trainees learn the basics of a method of psychotherapy before they are given supervision.


Genetic characterization of Hawaiian isolates of Plasmodium relictum reveals mixed-genotype infections.
The relatively recent introduction of a highly efficient mosquito vector and an avian pathogen (Plasmodium relictum) to an isolated island ecosystem with naïve, highly susceptible avian hosts provides a unique opportunity to investigate evolution of virulence in a natural system. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct impacts on virulence. Toward further understanding of how host-parasite and parasite-parasite relationships may impact virulence, this study characterizes within-host diversity of malaria parasite populations based on genetic analysis of the trap (thrombospondin-related anonymous protein) gene in isolates originating from Hawaii, Maui and Kauai Islands. A total of 397 clones were produced by nested PCR amplification and cloning of a 1664 bp fragment of the trap gene from two malarial isolates, K1 (Kauai) and KV115 (Hawaii) that have been used for experimental studies, and from additional isolates from wild birds on Kauai, Maui and Hawaii Islands. Diversity of clones was evaluated initially by RFLP-based screening, followed by complete sequencing of 33 selected clones. RFLP analysis of trap revealed a minimum of 28 distinct RFLP haplotypes among the 397 clones from 18 birds. Multiple trap haplotypes were detected in every bird evaluated, with an average of 5.9 haplotypes per bird. Overall diversity did not differ between the experimental isolates, however, a greater number of unique haplotypes were detected in K1 than in KV115. We detected high levels of clonal diversity with clear delineation between isolates K1 and KV115 in a haplotype network. The patterns of within-host haplotype clustering are consistent with the possibility of a clonal genetic structure and rapid within-host mutation after infection. Avian malaria (P. relictum) and Avipoxvirus are the significant infectious diseases currently affecting the native Hawaiian avifauna. This study shows that clonal diversity of Hawaiian isolates of P. relictum is much higher than previously recognized. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct implications for host demographics, disease management strategies, and evolution of virulence. The results of this study indicate a widespread presence of multiple-genotype malaria infections with high clonal diversity in native birds of Hawaii, which when coupled with concurrent infection with Avipoxvirus, may significantly influence evolution of virulence.


Metformin and Angiogenesis in Cancer - Revisited.
Several clinical studies demonstrated that diabetic patients treated with metformin were less likely to develop vascular complications, independent of glycemic control. It was also demonstrated that the large variety of metformin's vascular actions can be seen in nondiabetic conditions. Metformin has an interesting potential to treat vascular dysfunction and tumor angiogenesis in conditions beyond diabetes. Since metformin's use in cancer as a single antiangiogenic agent appears to be a therapeutic disappointment, the use of the drug as part of combination anticancer modality represents a therapeutic challenge. The normalization of vascular dysfunction as a new therapeutic strategy may provide better delivery of conventional anticancer agents to the tumor and disrupted tumor environment. In this review, we will outline the available information from the literature regarding metformin and tumor angiogenesis and suggest eventual experimental and clinical approaches.


Synthesis of transition metal dichalcogenide van der Waals heterostructures through chemical vapor deposition.
Transition metal dichalcogenide (TMD) van der Waals (vdW) heterostructures show great potential in the exploration of novel physical phenomena and practical applications. Compared to the traditional mechanical stacking techniques, chemical vapor deposition (CVD) method exhibits more advantages in preparing TMD vdW heterostructures. CVD enables the large-scale production of high-quality materials with clean interfaces in the future. Herein, CVD methods for the synthesis of TMD vdW heterostructures are summarized. These methods are categorized in two major strategies, multi-step process and one-step process. The effects of various factors are demonstrated, including the temperature, nucleation, and precursors. Finally, the remaining challenges are discussed.


Chaperone Mimetic Strategy for Achieving Organic Room-Temperature Phosphorescence based on Confined Supramolecular Assembly.
The development of organic materials that deliver room-temperature phosphorescence (RTP) is highly interesting for potential applications such as anticounterfeiting, optoelectronic devices, and bioimaging. Herein, a molecular chaperone strategy for controlling isolated chromophores to achieve high-performance RTP is demonstrated. Systematic experiments coupled with theoretical evidence reveal that the host plays a similar role as a molecular chaperone that anchors the chromophores for limited nonradiative decay and directs the proper conformation of guests for enhanced intersystem crossing through noncovalent interactions. For deduction of structure-property relationships, various structure-related descriptors that correlate with the RTP performance are identified, thus offering the possibility to quantitatively design and predict the phosphorescent behaviors of these systems. Furthermore, application in thermal printing is well realized for these RTP materials. The present work discloses an effective strategy for efficient construction of organic RTP materials, delivering a modular model which is expected to help expand the diversity of desirable RTP systems.


Identification of a novel β-adrenergic octopamine receptor-like gene (βAOR-like) and increased ATP-binding cassette B10 (ABCB10) expression in a Rhipicephalus microplus cell line derived from acaricide-resistant ticks.
The cattle tick Rhipicephalus (Boophilus) microplus is an economically important parasite of livestock. Effective control of ticks using acaricides is threatened by the emergence of resistance to many existing compounds. Several continuous R. microplus cell lines have been established and provide an under-utilised resource for studies into acaricide targets and potential genetic mutations associated with resistance. As a first step to genetic studies using these resources, this study aimed to determine the presence or absence of two genes and their transcripts that have been linked with acaricide function in cattle ticks: β-adrenergic octopamine receptor (βAOR, associated with amitraz resistance) and ATP-binding cassette B10 (ABCB10, associated with macrocyclic lactone resistance) in six R. microplus cell lines, five other Rhipicephalus spp. cell lines and three cell lines representing other tick genera (Amblyomma variegatum, Ixodes ricinus and Hyalomma anatolicum). End-point polymerase chain reaction (PCR) was used for detection of the βAOR gene and transcripts in DNA and RNA extracted from the tick cell lines, followed by capillary sequencing of amplicons. Quantitative real-time PCR (qPCR) was performed to determine the levels of expression of ABCB10. βAOR gene expression was detected in all Rhipicephalus spp. cell lines. We observed a second amplicon of approximately 220 bp for the βAOR gene in the R. microplus cell line BME/CTVM6, derived from acaricide-resistant ticks. Sequencing of this transcript variant identified a 36 bp insertion in the βAOR gene, leading to a 12-amino acid insertion (LLKTLALVTIIS) in the first transmembrane domain of the protein. In addition, nine synonymous SNPs were also discovered in R. appendiculatus, R. evertsi and R. sanguineus cell lines. Some of these SNPs appear to be unique to each species, providing potential tools for differentiating the tick species. The BME/CTVM6 cell line had significantly higher ABCB10 (P = 0.002) expression than the other R. microplus cell lines. The present study has identified a new βAOR gene and demonstrated a higher ABCB10 expression level in the BME/CTVM6 cell line, indicating that tick cell lines provide a useful experimental tool for acaricide resistance studies and further elucidation of tick genetics.


The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis?
There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for this "HDL hypothesis". In vitro studies suggest that HDL has a wide range of anti-atherogenic properties but validation of these functions in humans is absent to date. A significant number of animal studies and clinical trials support an atheroprotective role for HDL; however, most of these findings were obtained in the context of marked changes in other plasma lipids. Finally, genetic studies in humans have not provided convincing evidence that HDL genes modulate cardiovascular risk. Thus, despite a wealth of information on this intriguing lipoprotein, future research remains essential to prove the HDL hypothesis correct.


Effect of calcium hydroxide dressing on seal of permanent root filling.
Low apical leakage along root fillings following an application of calcium hydroxide was reported in a few methylene blue dye penetration studies. It has been found recently that methylene blue is decolored by calcium hydroxide, indicating that the short penetration of methylene blue may not be due to a tight seal only. Of the 80 roots of human maxillary central incisors used in this study, 40 roots (group 1) received calcium hydroxide root canal dressing whereas another 40 roots (group 2) did not. All the roots were then obturated with gutta-percha and Tubli-Seal sealer. Leakage along 20 filled roots in each group was measured using a modified fluid transport model at 48 h, 2, 4, 8 and 16 weeks after obturation; whereas leakage of another 20 filled roots in each group was measured using dye penetration with 1% methylene blue. Using the fluid transport model, no significant difference was found between the two groups at any time interval (P = 0.4847, 0.3875, 0.9490, 0.4786, 0.9148 respectively after 48 h, 2, 4, 8 and 16 weeks); using the methylene blue penetration method, leakage in group 1 (with root canal dressing) was significantly less than that in group 2 (without root canal dressing) (P = 0.0374). The contradiction in results from the different models indicated that problems existed with the models.