Tumor initiation inhibition through inhibition COX-1 activity of a traditional Korean herbal prescription, Geiji-Bokryung-Hwan, in human hepatocarcinoma cells.
Some Korean and oriental herbal prescriptions used for a syndrome expressed as chest paralysis and heartache are thought to be effective for angina pectoris. We investigated the effects of an oriental medicinal prescription, Geiji-Bokryung-Hwan (GBH) consisting of herbs of Cinnamomi Ramulus, Poria Cocos Hoelen (Pachymae Fungus), Moutan Cortex Radicis, Paeoniae Radix, and Persicae Semen, on growth-inhibitory activity and cancer chemopreventive activity in assays representing three major stages of carcinogenesis. The GBH was found to act as an potent inhibitor of cyclooxygenase (COX)-1 only but not as COX-2 inhibitor. Furthermore, the extract mediated anti-inflammatory effects and inhibited COX-associated hydroperoxidase functions (anti-promotion activity). Inhibitory effect of the GBH on the growth of cancer cell lines such as HepG2 cell and Hep3B cell was shown. These data suggest that GBH extracts merit investigation as a potential cancer chemopreventive agent in humans, especially in hepatological cancers.


Performance and measurement of a community-based distribution model of family planning services in Pakistan.
Community-based distribution (CBD) has been successfully applied to family planning (FP) services worldwide. It forms the basis for the large lady health worker (LHW) programme in Pakistan which serves a limited number of women with contraception services. Thus, the concept has seen limited application in Pakistan. We present the outcomes of a CBD model that was implemented in 49 districts across Pakistan by a non-government organization (NGO). The Marie Stopes Society (MSS) developed a CBD model around its fixed centres and reached around half a million married women of reproductive age (MWRA) with services. The services provided included outreach, counselling, condoms, pills, injections, and referrals for intrauterine contraceptive devices (IUCDs) and other reproductive health services. Services were provided in peri-urban locations for a subsidized fee using a businesslike target setting approach. The results of the programme were assessed by triangulating inception records against a cross-sectional end-of-project survey and service delivery records. The contraceptive prevalence rate (CPR) had increased from 38% to 51% by project-end with modern method use increasing by 50-200% and traditional method use remaining unchanged. Unmet need and self-reported pregnancy rates fell correspondingly. Approximately 73,500 new users were added to the initial user registered numbers to a total of 132,300; MSS accounted for 53,000 per year at the end of the project, which matched the commodities supplied by the NGO. The MSS CBD model presents a viable option for scaling effective FP services that may be replicated and scaled up with either donor support or by contracting out by the government. Triangulation of multiple data sources can provide more in-depth assessment of service delivery programmes and provide inferences that can inform service delivery.


Nurse-led sedation for transfemoral transcatheter aortic valve implantation seems safe for a selected patient population.
Transcatheter aortic valve implantation (TAVI) has become a high-volume procedure with increasing demands on hospital resources. Local anaesthesia with sedation supervised by an anaesthesiology team is the current standard of care. We aimed to describe our experience with a simplified, nurse-led sedation (NLS) protocol. This study enrolled 128 consecutive patients who underwent transfemoral TAVI with self-expandable Evolut R prosthesis between November 2019 and April 2021. Operators selected 50% of patients for NLS based on the clinical expectation of lower risk of procedural difficulties. Nurse-led sedation protocol demanded only mild to moderate levels of sedation. The clinical outcomes were determined from the local TAVI registry and the national mortality database. Baseline patient characteristics were similar in the NLS (n = 64) and anaesthesiologist-led sedation (ALS) (n = 64) groups except higher prevalence of diabetes mellitus (48.4% vs. 31.3%, P = 0.035) and peripheral vascular disease (20.3% vs. 7.8%, P = 0.036) in the ALS group. There was a trend for the larger prostheses used in the ALS group (P = 0.058). The procedural results did not differ, and coronary care team backup was rarely needed in the NLS group (6% of patients). The in-hospital outcomes were identical from both clinical and echocardiography perspectives, and 30-day mortality was low in both groups (1.5%). For the NLS group, preparation in the catheterization laboratory was quicker by 6.4 min (P = 0.01), and intensive care unit stay was shorter (2.03 vs. 3.48 days, P = 0.001). In conclusion, the NLS for the selected transfemoral TAVI population seems safe.


Characterization of 6α- and 6β-N-heterocyclic substituted naltrexamine derivatives as novel leads to development of mu opioid receptor selective antagonists.
As important pharmacological probes, highly selective opioid receptor antagonists are essential in opioid receptor structural characterization and opioid agonist functional studies. At present, a nonpeptidyl, highly selective, and reversible mu opioid receptor antagonist is still not available. Among a series of novel naltrexamine derivatives that have been designed and synthesized following molecular modeling studies, two compounds, NAP and NAQ, were identified as leads based on the results of in vitro and in vivo pharmacological assays. Both of them displayed high binding affinity and selectivity to the mu opioid receptor. Further pharmacokinetic and functional characterization revealed that NAP seems to be a peripheral nervous system agent while NAQ seems to be a central one. Such characteristics provide two distinguished potential application routes for these two agents and their derivatives. These results also supported our hypothesis that they may serve as leads to develop more potent and selective antagonists for the mu opioid receptor.


Root canal morphology of 1316 premolars from Brazilian individuals: an in vivo analysis using cone-beam computed tomography.
The aim of this study was to investigate the internal root canal anatomy of maxillary and mandibular premolars in a Brazilian subpopulation, in order to establish the prevalence of the different configurations proposed by Vertucci. Three hundred and ninety-eight cone-beam computed tomography scans were collected from a private imaging clinic database in Rio de Janeiro, including 217 maxillary and 226 mandibular scans. A total 1316 premolars (594 maxillary and 722 mandibular) were evaluated using an image viewer, and classified according to Vertucci. Two calibrated examiners determined the frequency of each morphological Type. A third examiner reviewed discordant cases. The Kappa test was applied to verify inter-rater agreement, and Fisher's Exact Test to verify gender-related differences. The most frequent root canal configurations of maxillary first and second premolars were Type IV (73.86%) and Type I (47.18%), respectively. Type I was the most prevalent in mandibular first and second premolars (80.59% and 95.86%, respectively). Only Types I and VIII presented a statistically significant difference between sexes. Type I was more frequent in females and Type VIII in males. A highly significant frequency of Type I was found in both mandibular first and second premolars, whereas the most frequent maxillary premolar root canal configuration was Type IV for first premolars and Type I for second premolars.


Evidence for autocatalytic cross-linking of hydroxyproline-rich glycoproteins during extracellular matrix assembly in Volvox.
The alga Volvox carteri is one of the simplest multicellular organisms, yet it has a surprisingly complex extracellular matrix (ECM), making Volvox suitable as a model system in which to study ECM self-assembly. Here, we analyze the primary structures and post-translational modifications of two main ECM components synthesized in response to sexual induction as well as wounding. These proteins are members of the pherophorin family with as yet unknown properties. They contain polyhydroxyproline spacers as long as 500 and 2750 residues. Even the highly purified proteins retain the capacity to self-assemble and cross-link, producing an insoluble fibrous network in an apparently autocatalytic reaction. This pherophorin-based network is located within the deep zone of the ECM. A molecular genetic search for additional members of the pherophorin family indicates that at least nine different pherophorin species can be expected to serve as precursors for ECM substructures. Therefore, the highly diversified members of the pherophorin family represent region-specific morphological building blocks for ECM assembly and cross-linking.


Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue.
The arachnoid granulations (AGs) are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF) to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7-10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7-10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144) and their expression was quantified using flow cytometry analysis. Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. To our knowledge, this is the first report of the in vitro culture of arachnoidal cells grown from human AG tissue. We demonstrated that these cells in vitro continue to express some of the cytoskeletal and junctional proteins characterized previously in human AG tissue, such as proteins involved in the formation of gap junctions, desmosomes, epithelial specific adherens junctions, as well as tight junctions. These junctional proteins in particular may be important in allowing these arachnoidal cells to regulate CSF outflow.


Non-Hodgkin's Lymphoma in the Oral Cavity.
We report a case of a diffuse large B-cell lymphoma of the maxilla. A patient presented with diffuse swelling of the right maxillary region following the extraction of an upper right maxillary tooth. The patient was referred for cone beam computed tomography (CBCT) to visualize the area in question in three dimensions. A massive destructive maxillary lesion was noted on CBCT examination suggestive of an aggressive lesion highly suspicious for a malignancy. A subsequent biopsy and immunochemistry were useful in confirming the diagnosis.


* Understanding the Spatiotemporal Degradation Behavior of Aggrecanase-Sensitive Poly(ethylene glycol) Hydrogels for Use in Cartilage Tissue Engineering.
Enzyme-sensitive hydrogels are promising cell delivery vehicles for cartilage tissue engineering. However, a better understanding of their spatiotemporal degradation behavior and its impact on tissue growth is needed. The goal of this study was to combine experimental and computational approaches to provide new insights into spatiotemporal changes in hydrogel crosslink density and extracellular matrix (ECM) growth and how these changes influence the evolving macroscopic properties as a function of time. Hydrogels were designed from aggrecanase-sensitive peptide crosslinks using a simple and robust thiol-norbornene photoclick reaction. To study the influence of variations in cellular activity of different donors, chondrocytes were isolated from either juvenile or adult bovine donors. Initial studies were performed to validate and calibrate the model against experiments. Through this process, two key features were identified. These included spatial variations in the hydrogel crosslink density in the immediate vicinity of the cell and the presence of cell clustering within the construct. When these spatial heterogeneities were incorporated into the computational model along with model inputs of initial hydrogel properties and cellular activity (i.e., enzyme and ECM production rates), the model was able to capture the spatial and temporal evolution of ECM growth that was observed experimentally for both donors. In this study, the juvenile chondrocytes produced an interconnected matrix within the cell clusters leading to overall improved ECM growth, while the adult chondrocytes resulted in poor ECM growth. Overall, the computational model was able to capture the spatiotemporal ECM growth of two different donors and provided new insights into the importance of spatial heterogeneities in facilitating ECM growth. Our long-term goal is to use this model to predict optimal hydrogel designs for a wide range of donors and improve cartilage tissue engineering.


Developing Culturally Sensitive mHealth Apps for Caribbean Immigrant Women to Use During Pregnancy: Focus Group Study.
A valuable addition to the mobile health (mHealth) space is an exploration of the context of minorities in developed countries. The transition period postmigration, culture, and socioeconomic uniqueness of migratory groups can shed light on the problems with existing prenatal mHealth apps. The objectives of this study were to (1) use the theoretical concept of pregnancy ecology to understand the emotional, physical, information, and social challenges affecting low-income Caribbean immigrant women's prenatal well-being practices and (2) develop a deep understanding of challenges worthy of consideration in mHealth design for these women. This qualitative interpretive approach using analytical induction presents the findings of 3 focus group sessions with 12 Caribbean immigrant women living in South Florida in the United States. The study took place from April to September 2015. The participants revealed problematic tiers and support needs within the pregnancy ecology including emotional stressors caused by family separation, physical challenges, information gaps, and longing for social support. mHealth interventions for low-income Caribbean immigrant women must be designed beyond the conventional way of focusing on the events surrounding the unborn child. It can be tailored to the needs of the expecting mother. Pregnancy information should be customized on the basis of the variability of lifestyle, cultural practices, socioeconomic status, and social ties while still being able to deliver appropriate guidelines and clear cultural misconceptions.


Spino-pelvic alignment after surgical correction for developmental spondylolisthesis.
This study is a retrospective multi-centre analysis of changes in spino-pelvic sagittal alignment after surgical correction of L5-S1 developmental spondylolisthesis. The purpose of this study was to determine how sagittal spino-pelvic alignment is affected by surgery, with the hypothesis that surgical correction at the lumbo-sacral level is associated with an improvement in the shape of the spine and in the orientation of the pelvis. Whether L5-S1 high grade spondylolisthesis should or should not be reduced remains a controversial subject. A popular method of treatment has been in situ fusion, but studies have reported a high rate of pseudarthrosis, slip progression and persistent cosmetic deformity. Spinal instrumentation with pedicle screws has generated a renewed interest for reduction, but the indications for this treatment and its effect on spino-pelvic alignment remain poorly defined. Recent evidence indicates that reduction might be indicated for subjects with an unbalanced (retroverted or vertical) pelvis. This is a retrospective multi-centre analysis of 73 subjects (mean age 18 +/- 3 years) with developmental spondylolisthesis and an average follow-up of 1.9 years after reduction and posterior fusion with spinal instrumentation or cast immobilisation. Spinal and pelvic alignment were measured on standing lateral digitised X-rays using a computer software allowing a very high inter and intra observer reliability. Pelvic incidence was unaffected by surgery. The most important changes were noted for grade, L5 Incidence, lumbo-sacral-angle, and lumbar lordosis, which all decreased significantly towards normal adult values. At first evaluation, pelvic tilt, sacral slope and thoracic kyphosis appeared minimally affected by surgery. However, after classifying subjects into balanced and unbalanced pelvis, significant improvements were noted in pelvic alignment in both the sub-groups, with 40% of cases switching groups, the majority from an unbalanced to a balanced pelvis alignment. The direction and magnitude of these changes were significantly different by sub-group: sacral slope decreased in the balanced pelvis group but increased in the unbalanced group, while pelvic tilt values did the opposite. While pelvic shape is unaffected by attempts at surgical reduction, proper repositioning of L5 over S1 significantly improves pelvic balance and lumbar shape by decreasing the abnormally high lumbar lordosis and abnormal pelvic retroversion. These results emphasise the importance of sub-dividing subjects with high grade developmental spondylolisthesis into unbalanced and balanced pelvis groups, and further support the contention that reduction techniques might be considered for the unbalanced retroverted pelvis sub-group.


Acoustomicrofluidic application of quasi-shear surface waves.
The paper analyzes the possibility of using predominantly boundary polarized surface acoustic waves for actuating fluidic effects in microchannels fabricated inside containers made of PDMS. The aim is to remove a shortcoming peculiar to conventionally utilized predominantly vertically polarized waves. Such waves strongly attenuate while they propagate under container side walls because of the leakage into them. Due to a specific feature of PDMS - extremely small shear elastic modulus - losses of boundary polarized modes should be far smaller. The amplitude of vertical mechanical displacements can be increased right inside the channel owing to the scattering of acoustic fields. As an example, the predominantly vertically polarized surface wave on 128YX LiNbO3 is compared with the quasi-shear leaky wave on 64YX LiNbO3. Our computations predict that, given the electric power supplied to the launching transducer, the quasi-shear wave will drive the fluid more efficiently than the surface wave on 128YX LiNbO3 when the container wall thickness is larger than 25-30 wavelengths, if there are no additional scatterers inside the channel. In the presence of a scatterer, such as a thin gold strip, the quasi-shear wave can be more efficient when the wall thickness exceeds 10-15 wavelengths.


Attitudes toward influenza vaccination in healthcare workers in Italy: A systematic review and meta-analysis.
Healthcare workers (HCWs) are among the at-risk groups for whom influenza vaccination is strongly recommended. To assess the proportion of Italian HCWs with positive attitudes toward influenza vaccination, we conducted a systematic review of relevant literature and a meta-analysis. Our focus was on the influenza seasons from 2017/18 to 2021/22. The prevalence of favorable attitudes toward vaccination varied, ranging from 12% during the 2017/18 influenza season to 59% in the 2020/21 season. The significant increase in the 2020/21 season can be attributed to adaptations necessitated by the COVID-19 pandemic. During the 2021/22 influenza season, there was a decline in vaccination coverage (37%), likely due to the absence of a robust preventive culture. Various strategies have been employed to enhance HCWs' attitudes to achieve higher vaccination rates, but none of them have demonstrated satisfactory results. Policymakers should consider implementing a policy of mandatory vaccination to ensure elevated vaccination coverage among HCWs.


Mapping and transcriptional properties of RT1 class II region genes.
The class II region of major histocompatibility complex of the rat. Rattus norvegicus (RT1) consists of RT1.B, RT1.D, and RT1.H subregions. The gene order around the H subregion was determined as RT1.A--H beta-H alpha--B by RFLP analysis of naturally occurring intra-RT1 recombinant rats with HLA DP probes. A unique recombinant strain, LEJ, was found to have its recombinational site between H beta and H alpha (RT1.AuH beta uH alpha bBbDb). Northern analysis of class II mRNAs showed that transcripts of RT1.D alpha, RT1.D beta, and RT1.B alpha shared identical sizes among various strains of rats, but RT1.B beta mRNA showed allele-specific size heterogeneities. Northern hybridization with HLA DP alpha probes detected possible RT1.H alpha transcripts. On the other hand, no clear signal of H beta was observed. BDIX whose RT1.B products had not been identified was found to transcribe B alpha and B beta mRNAs.


[Immunologic mechanisms and the effect of immunosuppressive therapy in ophthalmology].
The authors mention some immunopathological mechanisms which participate in the beginning and maintenance of activity in so-called idiopathic endogenous uveitis. They draw attention to the possibility to influence these mechanisms by immunosuppressive treatment, mention its advantages and the feasibility of risk of undesirable side-effects. The authors assume that it is useful to use corticoids and cytotoxic substances as well as the more aimed action on immunity exerted by Cyclosporine A.


Nitric oxide pathway counteracts enhanced contraction to membrane depolarization in aortic rings of rats on high-sodium diet.
Vascular smooth muscle cell contraction and endothelium-dependent relaxation was evaluated in aortic rings isolated from weaned, 5-mo-old Sprague-Dawley rats fed a normal (NS; 0.8% NaCl) or high (HS; 8% NaCl) sodium diet. Arterial pressure was 140 +/- 6 (NS) and 145 +/- 6 mmHg (HS). In endothelium-denuded rings, the response to phenylephrine (PE) was not modified by the sodium diet, while that of depolarizing agent KCl and intracellular calcium releasing agent caffeine increased in the HS group. When endothelium was preserved, PE-evoked contraction was reduced in both NS and HS groups, the contraction being yet lower in the HS group. This effect was partially obliterated by addition of N(G)-nitro-L-arginine methyl ester (L-NAME), independently of the sodium diet. Relaxation to ACh in intact rings and to sodium nitroprusside (SNP) and 8-bromoadenosine 3'5' cyclic guanosine monophosphate (8-BrcGMP) in the absence of endothelium was enhanced in rings isolated from HS rats. In addition, the dose-response curve to 8-BrcGMP was shifted to the right in the presence of iberiotoxin, an inhibitor of large conductance, voltage-dependent, and calcium-sensitive potassium channel (BK(Ca)). However, shift was more marked in rings from HS rats. Present results provide evidence that response of vascular smooth muscle cell to nitric oxide/cGMP-related compounds is increased in HS rings and is associated with a greater activation of the repolarizing BK(Ca) channels. Such changes might counterbalance enhanced contractile response to membrane depolarization and thus participate in maintenance of arterial pressure in the present model of early and long-term HS feeding in rats.


The public health exposome: a population-based, exposure science approach to health disparities research.
The lack of progress in reducing health disparities suggests that new approaches are needed if we are to achieve meaningful, equitable, and lasting reductions. Current scientific paradigms do not adequately capture the complexity of the relationships between environment, personal health and population level disparities. The public health exposome is presented as a universal exposure tracking framework for integrating complex relationships between exogenous and endogenous exposures across the lifespan from conception to death. It uses a social-ecological framework that builds on the exposome paradigm for conceptualizing how exogenous exposures "get under the skin". The public health exposome approach has led our team to develop a taxonomy and bioinformatics infrastructure to integrate health outcomes data with thousands of sources of exogenous exposure, organized in four broad domains: natural, built, social, and policy environments. With the input of a transdisciplinary team, we have borrowed and applied the methods, tools and terms from various disciplines to measure the effects of environmental exposures on personal and population health outcomes and disparities, many of which may not manifest until many years later. As is customary with a paradigm shift, this approach has far reaching implications for research methods and design, analytics, community engagement strategies, and research training.


Non-Extensive Fragmentation of Natural Products and Pharmacophore-Based Virtual Screening as a Practical Approach to Identify Novel Promising Chemical Scaffolds.
Fragment-based drug design (FBDD) and pharmacophore modeling have proven to be efficient tools to discover novel drugs. However, these approaches may become limited if the collection of fragments is highly repetitive, poorly diverse, or excessively simple. In this article, combining pharmacophore modeling and a non-classical type of fragmentation (herein called non-extensive) to screen a natural product (NP) library may provide fragments predicted as potent, diverse, and developable. Initially, we applied retrosynthetic combinatorial analysis procedure (RECAP) rules in two versions, extensive and non-extensive, in order to deconstruct a virtual library of NPs formed by the databases Traditional Chinese Medicine (TCM), AfroDb (African Medicinal Plants database), NuBBE (Nuclei of Bioassays, Biosynthesis, and Ecophysiology of Natural Products), and UEFS (Universidade Estadual de Feira de Santana). We then developed a virtual screening (VS) using two groups of natural-product-derived fragments (extensive and non-extensive NPDFs) and two overlapping pharmacophore models for each of 20 different proteins of therapeutic interest. Molecular weight, lipophilicity, and molecular complexity were estimated and compared for both types of NPDFs (and their original NPs) before and after the VS proceedings. As a result, we found that non-extensive NPDFs exhibited a much higher number of chemical entities compared to extensive NPDFs (45,355 vs. 11,525 compounds), accounting for the larger part of the hits recovered and being far less repetitive than extensive NPDFs. The structural diversity of both types of NPDFs and the NPs was shown to diminish slightly after VS procedures. Finally, and most interestingly, the pharmacophore fit score of the non-extensive NPDFs proved to be not only higher, on average, than extensive NPDFs (56% of cases) but also higher than their original NPs (69% of cases) when all of them were also recognized as hits after the VS. The findings obtained in this study indicated that the proposed cascade approach was useful to enhance the probability of identifying innovative chemical scaffolds, which deserve further development to become drug-sized candidate compounds. We consider that the knowledge about the deconstruction degree required to produce NPDFs of interest represents a good starting point for eventual synthesis, characterization, and biological activity studies.


[Semen quality of normal fertile men].
To study the semen quality of confirmed fertile men with the time to pregnancy (TTP) of 12 months or less, and analyze the correlation of semen parameters with TTP. We recruited 1 152 men aged 18 -50 years and with TTP of 12 months. We used questionnaire investigation, physical examination and semen analysis, calculated the normal reference ranges of semen parameters, and analyzed the effects of TTP and other biological characteristics on semen quality. Seminal examinations showed that the semen volume was 1.5 ml, sperm concentration 17 million per ml, total sperm number 39 million per ejaculate, total sperm motility 41%, progressive sperm motility 33%, normal sperm morphology 5.0%, sperm vitality 53%, and total number of progressively motile sperm 17 million per ejaculate in the 1 152 subjects. In comparison, the total number of progressively motile sperm was significantly smaller in those aged > or = 35 years (P < 0.01), morphologically normal sperm were markedly less in those with BMI > 25.0 (P < 0.01), and sperm concentration, total number of sperm, morphologically normal sperm rate and total number of progressively motile sperm were remarkably lower in those with BMI < 18. 5 (P < 0.05). Cigarette smoking significantly reduced the sperm volume (P < 0.01), and drinking (> 10 g per week) decreased the sperm volume and the total numbers of sperm, morphologically normal sperm and progressively motile perm (P < 0.05). TTP was negatively correlated with sperm concentration, total number of sperm and total number of progressively motile sperm (P < 0.01). The subjects with sexual abstinence of 5 -7 days showed markedly higher sperm concentration, total number of sperm and total number of progressively motile sperm than others (P < 0.01). In normal fertile men, the fifth centile of semen parameters is close to the WHO normal reference range, TTP is negatively correlated with semen quality, and age, BMI and lifestyle may affect some of the semen parameters.


[Comperative characteristics of different organizational approaches to the provision of dental care in Ukraine and Slovakia].
Saving dental health is a priority, which is controlled by the European strategy for the World Health Organization to achieve ≪Health for All≫. To study and compare organizational approaches to the organization of dental care in Ukraine and Slovakia. In the course of the work we used statistical, bibliosemantic methods and the method of structural and logical analysis, the data of the statistical branch reporting of Ukraine, Slovakia and the data of the European database ≪Health for All≫ were used. It is established that the provision of the population with educational institutions for future dentists in Ukraine is one university for 2154566 people, and in Slovakia - one for 676 764 people. Obviously, access to dental education in the Slovak Republic is better than in Ukraine. In the course of the study, we found that the level of provision of dentists for 10 thousand people in Ukraine is 4.56, and in Slovakia-5.75, which is 26% more than in Ukraine. In Slovakia, the level of availability of dentists is 5.75, too, with a reliable difference in the profile of administrative territories Conclusion. Both countries are working to achieve international goals to ensure dental health for the period till 2025. Therefore, the exchange of good experience, which gained in Ukraine and Slovakia for the organization of dental care will improve the performance of dental services of both countries to achieve these goals.


Plasmodium vivax induced myocarditis: a rare case report.
Malaria is one of the commonest parasitic disease in the tropics since ages. However the plasmodium still continues to give surprises to all of us. In the similar context we report a case of Plasmodium vivax induced myocarditis in a 20 year old male and review the literature related to this rare entitiy.


A meta-analysis of the efficacy of music therapy for premature infants.
This meta-analysis on music research with premature infants in neonatal intensive care units (NICU) showed an overall large, significant, consistent effect size of almost a standard deviation (d =.83) (Cohen, 1998). Effects were not mediated by infants' gestational age at the time of study, birthweight, or type of music delivery nor by physiologic, behavioral, or developmental measures of benefit. The homogeneity of findings suggests that music has statistically significant and clinically important benefits for premature infants in the NICU. The unique acoustic properties that differentiate music from all other sounds are discussed and clinical implications for research-based music therapy procedures cited.


Body mass index and alcohol use.
Obesity, inactivity and being overweight are leading causes of morbidity and mortality in the United States. The relationship between eating, overeating, and addiction have been discussed, debated and more recently investigated. We have hypothesized that drugs of abuse compete with food for brain reward sites. Overeating and obesity may act as protective factors reducing drug reward and addiction. In the first part of this study, 374 charts of all active weight management patients in a 12-month period were examined. Demographic information, laboratory testing, psychiatric diagnostic interview, alcohol and drug history were reviewed. A detailed alcohol use, abuse, dependence history was present in 298 charts as part of the pre-bariatric evaluation. The relationship between BMI and alcohol use among female patients (n = 298) was then analyzed. We found a significant (p <.05) inverse relationship between BMI and alcohol consumption. The more obese the patient was, the less alcohol they consumed. The percentage of women who consumed alcohol in the past year decreased as BMI level increased. These results confirmed our surgeons' perception that it is rare to find a morbidly obese patient excluded for bariatric surgery because of excessive alcohol consumption. Obese patients have lower rates of alcohol use than found in the general population of women. As BMI increases, lower rates of alcohol consumption are found. Overeating may compete with alcohol for brain reward sites, making alcohol ingestion less reinforcing.


Longitudinal relationships between cardiovascular events, risk factors, and time-dependent sleep duration.
Although many studies have evaluated the relationships between sleep duration and cardiovascular (CV) events/risk factors, longitudinal associations with time-dependent sleep duration have not been adequately assessed. A retrospective, longitudinal study was conducted involving individuals aged 20 years or older that received annual health check-ups at St. Luke's International Hospital from 2005 to 2010. Data collection included self-reported demographic, clinical and health habit information (including sleep duration; < 6, 6-7, 7-8, ≥ 8 h), baseline examinations, and laboratory measures for each year. We conducted mixed effects analyses to examine the associations between non-fatal CV events, risk factors, and time-dependent sleep duration longitudinally. Of the total of 31,830 participants enrolled, 70.1% of participants changed their sleep dura-tion, and 365 participants experienced CV events during follow-up periods. Compared to those reporting 7-8 h of sleep, those reporting less than 6 h of sleep were significantly more likely to experience non-fatal CV events (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.03-3.07; p = 0.04), but other groups were not (OR 1.12; 95% CI 0.70-1.77; p = 0.64 for 6-7 h and OR 1.22; 95% CI 0.68-2.23; p = 0.50 for ≥ 8 h). The shortest sleep duration was associated with a higher likelihood of obesity/overweight status (OR 1.49; 95% CI 1.32-1.69; p < 0.01). Individuals reporting less than 6 h of sleep were significantly more likely to have non-fatal CV events than those reporting 7-8 h of sleep. For the risk factors, short sleep duration was associ-ated with obesity/overweight status.


Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid.
Humans are genetically unable to produce the sialic acid N-glycolylneuraminic acid (Neu5Gc), because of a mutation that occurred after our last common ancestor with great apes. Although Neu5Gc is presumed absent from normal humans, small amounts have been claimed to exist in human tumors and fetal meconium. We have generated an antibody with high specificity and avidity for Neu5Gc. Fetal tissues, normal adult tissues, and breast carcinomas from humans showed reactivity to this antibody, primarily within secretory epithelia and blood vessels. The presence of small amounts of Neu5Gc was confirmed by MS. Absent any known alternate pathway for its synthesis, we reasoned that these small amounts of Neu5Gc might originate from exogenous sources. Indeed, human cells fed with Neu5Gc incorporated it into endogenous glycoproteins. When normal human volunteers ingested Neu5Gc, a portion was absorbed and eliminated in urine, and small quantities were incorporated into newly synthesized glycoproteins. Neu5Gc has never been reported in plants or microbes to our knowledge. We found that Neu5Gc is rare in poultry and fish, common in milk products, and enriched in red meats. Furthermore, normal humans have variable amounts of circulating IgA, IgM, and IgG antibodies against Neu5Gc, with the highest levels comparable to those of the previously known anti-alpha-galactose xenoreactive antibodies. This finding represents an instance wherein humans absorb and metabolically incorporate a nonhuman dietary component enriched in foods of mammalian origin, even while generating xenoreactive, and potentially autoreactive, antibodies against the same molecule. Potential implications for human diseases are briefly discussed.


Successful treatment of gastrointestinal mucormycosis in an adult with acute leukemia: case report and literature review.
Mucormycosis has emerged as an important cause of invasive fungal infection in patients with hematologic malignancies. Gastrointestinal mucormycosis is an unusual presentation of this invasive fungal infection, and it causes considerable morbidity and mortality. Such outcomes are due in part to a nonspecific presentation that results in delays in diagnosis and treatment. Successful treatment of gastrointestinal mucormycosis involves surgical debridement and appropriate antifungal therapy.


Epidemiological features and clinical manifestations of Lyme borreliosis in Korea during the period 2005-2012.
Lyme borreliosis is one of the most common tick-borne infections in the northern hemisphere. However, the epidemiological features and clinical manifestations of this disease in Korea are unknown. The present study is the first to investigate the characteristics of Lyme borreliosis in Korea. We traced suspected cases of Lyme borreliosis during the period 2005-2012. Of the 16 identified patients with the disease, 11 had acquired autochthonous infection within Korea, while 5 patients were infected outside Korea. The history of past exposure was investigated in 8 of the 11 patients with autochthonous infection; 5 of these 8 patients (62.5%) were suspected to have acquired the infection in the northeastern alpine region. Clinically, of 11 patients with autochthonous infection, 6 (54.5%) showed early skin manifestations, 4 (36.4%) showed neurological manifestations, and 1 (9.1%) showed acrodermatitis chronica atrophicans. In conclusion, Lyme borreliosis could be endemic in the northeastern alpine region of Korea, and neurological and early skin manifestations are likely to be the major clinical characteristics of autochthonous Lyme borreliosis in Korea.


Placenta and maternal endothelium during preeclampsia: Disruption of the glycocalyx explains increased inositol phosphoglycans and angiogenic factors in maternal blood.
The etiology of the pregnancy syndrome preeclampsia is still unclear, while most hypotheses center on the placenta as the major contributor of the syndrome. Especially changes of the placental metabolism, including the use of glucose to produce energy, are important features. As an example, inositol phosphoglycan P-type molecules, second messengers involved in the glucose metabolism of all cells, can be retrieved from maternal urine of preeclamptic women, even before the onset of clinical symptoms. Alterations in the placental metabolism may subsequently lead to negative effects on the plasma membrane of the placental syncytiotrophoblast. This in turn may have deleterious effects on the glycocalyx of this layer and a disruption of this layer in all types of preeclampsia. The interruption of the glycocalyx in preeclampsia may result in changes of inositol phosphoglycan P-type signaling pathways and the release of these molecules as well as the release of soluble receptors such as sFlt-1 and sEndoglin. The release of placental factors later affects the maternal endothelium and disrupts the endothelial glycocalyx as well. This in turn may pave the way for edema, endothelial dysfunction, coagulation, all typical symptoms of preeclampsia.


Artificial membranes for membrane protein purification, functionality and structure studies.
Membrane proteins represent one of the most important targets for pharmaceutical companies. Unfortunately, technical limitations have long been a major hindrance in our understanding of the function and structure of such proteins. Recent years have seen the refinement of classical approaches and the emergence of new technologies that have resulted in a significant step forward in the field of membrane protein research. This review summarizes some of the current techniques used for studying membrane proteins, with overall advantages and drawbacks for each method.


Association between fasting blood glucose and outcomes and mortality in acute ischaemic stroke patients with diabetes mellitus: a retrospective observational study in Wuhan, China.
To evaluate the predictive value of fasting blood glucose (FBG) on unfavourable outcomes and mortality in diabetes mellitus (DM) patients after acute ischaemic stroke (AIS). A hospital-based observational cohort study was conducted. Clinical data, including sex, age, body mass index, vascular risk factors and systolic/diastolic blood pressure, were routinely collected. National Institutes of Health Stroke Scale score was used to assess stroke severity on admission. FBG was determined on the first day after fasting for at least 8 hours. The modified Rankin Scale was used to assess functional outcome at 90 days: 3-6, unfavourable outcome and 6, death. Renmin Hospital of Wuhan University, Wuhan, China. Patients who had AIS with DM, who were consecutively admitted within 24 hours of onset from January 2018 to June 2019. For the 568 patients, the median age was 65 years (IQR, 55-74 years). There were 377 (66.4%) men. The median FBG values were 7.37 mmol/L (IQR, 5.99-10.10 mmol/L), and the median glycated haemoglobin (HbA1c) values were 6.6 (IQR, 5.8-8.3). Multivariable logistic and Cox regression analysis of confounding factors showed that FBG at the time of admission was an independent predictor of unfavourable outcome (OR, 1.25 (1.14-1.37); p<0.0001) and mortality (HR, 1.10 (1.03-1.15); p<0.05) at 90 days after onset. Time to death was analysed by Kaplan-Meier curves based on FBG quartiles. The risk of death in the two highest quartile groups (FBG, 7.38-10.10 mmol/L; FBG, ≥10.11 mmol/L) was significantly higher than that in the two lowest quartile groups (FBG, ≤6.00 mmol/L; FBG, 6.01-7.37 mmol/L; p<0.0001). Higher FBG levels are associated with unfavourable outcomes and mortality in Chinese patients who had AIS with DM. Our data contribute to the knowledge regarding the relationship between FBG and prognosis in patients with DM who had AIS.


Evaluating Student Attitudes: Perceptions of Interprofessional Experiences Following Participation in a Student-Run Free Clinic.
It is increasingly evident that patient health outcomes are improved when they are treated by an effective interdisciplinary healthcare team. Many also endorse that learning to function collaboratively in interdisciplinary settings should start at the onset of one's medical education. Student-run free clinics, such as the University of Central Florida College of Medicine's (UCF COM) KNIGHTS (Keeping Neighbors In Good Health Through Service) Clinic, provide opportunities for students to work in concert with other healthcare professionals. This study aimed to discern whether volunteering in this setting had a positive impact on medical students' perception of working within an interdisciplinary team. A single survey was distributed via Qualtrics to all first and second-year medical students (N = 248) at the UCF COM. The items of interest examined in this study were part of a larger study described elsewhere. The mean responses on a 5-point Likert-like scale to these survey items were recorded and compared between two cohorts: KNIGHTS volunteers and non-volunteers. One hundred twenty-three (49.6%) students responded to the survey and most items showed no statistically significant difference between the two groups (p-value > 0.05). However, there were a few items of interest that did show a significant difference. These included KNIGHTS volunteers being much more likely to have worked with other healthcare professionals (p < 0.001) as well as believing themselves to have a better understanding of the role of medicine within an interprofessional team (p = 0.016). Additionally, KNIGHTS volunteers were more likely to feel like they understood the role of patient education (p = 0.031) and pharmacy (p = 0.040) within an interprofessional team. Interestingly, KNIGHTS volunteers were also more likely to believe that problem-solving skills should be learned with students within their own discipline (p = 0.009) as well as that there is little overlap between the roles of medical students and students from other healthcare disciplines (p = 0.044). Still, overall results showed that both volunteers and non-volunteers had an overall positive perception of interdisciplinary teams and working with other healthcare professionals.


Circadian PER2::LUC rhythms in the olfactory bulb of freely moving mice depend on the suprachiasmatic nucleus but not on behaviour rhythms.
The temporal order of physiology and behaviour in mammals is regulated by the coordination of the master circadian clock in the suprachiasmatic nucleus (SCN) and peripheral clocks in various tissues outside the SCN. Because the circadian oscillator(s) in the olfactory bulb (OB) is regarded as SCN independent, we examined the relationship between the SCN master clock and the circadian clock in the OB. We also examined the role of vasoactive intestinal peptide receptor 2 in the circadian organization of the OB. We continuously monitored the circadian rhythms of a clock gene product PER2 in the SCN and OB of freely moving mice by means of a bioluminescence reporter and an optical fibre implanted in the brain. Robust circadian rhythms were detected in the OB and SCN for up to 19 days. Bilateral SCN lesions abolished the circadian behaviour rhythms and disorganized the PER2 rhythms in the OB. The PER2 rhythms in the OB showed more than one oscillatory component of a similar circadian period, suggesting internal desynchronization of constituent oscillators. By contrast, significant circadian PER2 rhythms were detected in the vasoactive intestinal peptide receptor 2-deficient mice, despite the substantial deterioration or abolition of circadian behavioural rhythms. These findings indicate that the circadian clock in the OB of freely moving mice depends on the SCN master clock but not on the circadian behavioural rhythms. The circadian PER2::LUC rhythm in the cultured OB was as robust as that in the cultured SCN but reset by slice preparation, suggesting that culturing of the slice reinforces the circadian rhythm.


[Purification, characterization and application of ε-poly-L. lysine- degrading enzyme from Streptomyces sp. M-Z18 ].
[OBJECTIVE] The ε-poly-L-lysine-degrading enzyme (Pld) derived from Streptomyces sp. M-Z18 was purified and characterized. Furthermore, Pld was used to produce the low polymerization of ε-poly-L-lysine (ε-PL). [METHODS] Pld was purified to electrophoretical homogeneity through HiTrapTM Butyl HP hydrophobic chromatography after pretreated by ultrasonic and NaSCN dissolving. Subsequently, enzymatic characteristics, kinetic parameters and the time profile of ε-PL degradation by the purified Pld were studied. Meanwhile, we examined the effect of ε-PL with different degrees of polymerization on the minimal inhibitory concentration of bacteria and fungi. [RESULTS] Pld was purified to homogeneity with a final fold of 80.4 and an overall yield of 59.3%. The optimal temperature and pH for the purified Pld were 370C and 7. 0, respectively. Moreover, the Km with L-lysyl-p-nitroanilide as substrate was calculated to be 0. 621 mmol/L, and the Vmax was 701. 16 nmol/min.mg. Pld was stable in the range of pH 7. 0 - 10. 0, and temperature up to 500 C, respectively. Time profile of ε-PL degradation by the purified Pld indicated that Pld catalyzed endo-type degradation of ε- PL. The experiments of minimal inhibitory showed that ε-PL with high degree of polymerization (30 - 35) had a superior antibacterial effect on bacteria and the low degree of polymerization ε-PL (8 -20) had a better antibacterial effect on yeasts. However, ε-PL with various degrees of polymerization had a poor antibacterial effect on mould. [ CONCLUSION] The present result showed that an endo-type Pld from ε-PL-producing strain was purified. Meanwhile, it is proved that ε-PL with different degrees of polymerization have exhibited significant different antibacterial effects on microorganism.


[Treatment with clonidine in a case of the short bowel syndrome with therapy-refractory diarrhea].
A patient with refractory diarrhoea (up to 10 l/d) following colectomy and ileostomy was treated with clonidine, after loperamide, tinctura opii, cholestyramine and somatostatin had failed to reduce stool volume to less than 6 l/d. Under combined treatment with clonidine (1200 micrograms/d) and somatostatin (6 mg/d), which was well tolerated, stool weights were normalised within 24 hours. This case report on the successful anti-diarrhoeic effect of clonidine is completed by experimental data from rat jejunal and duodenal segments. In the presence of the adenylate cyclase-stimulating agent forskolin, clonidine normalised both mucosal cAMP content and cAMP-induced hypersecretion in rat intestine. This suggests that the anti-diarrhoeic effect of clonidine in-vitro results from an alpha 2-receptor mediated inhibition of the stimulated adenylate cyclase. Case report and experimental data therefore support the theory that therapeutical application of clonidine in diarrhoea may be successful.


The Agrobacterium VirD5 protein hyperactivates the mitotic Aurora kinase in host cells.
Aided by translocated virulence proteins, Agrobacterium tumefaciens transforms plant cells with oncogenic T-DNA. In the host cells the virulence protein VirD5 moves to the nucleus, where it becomes localized at the kinetochores, and disturbs faithful chromosome segregation, but the molecular mechanism underlying this remains unknown. To gain more insight, we screened amongst the kinetochore proteins for VirD5 interactors using bimolecular fluorescence complementation assays, and tested chromosome segregation in yeast cells. We found that VirD5 interacts with the conserved mitotic Aurora kinase Ipl1 in yeast and likewise with plant Aurora kinases. In vitro VirD5 was found to stimulate the activity of Ipl1. Phosphorylation of substrates by Ipl1 in vivo is known to result in the detachment between kinetochore and spindle microtubule. This is necessary for error correction, but increased Ipl1/Aurora kinase activity is known to cause spindle instability, explaining enhanced chromosome mis-segregation seen in the presence of VirD5. That activation of the Ipl1/Aurora kinase at least partially underlies the toxicity of VirD5 became apparent by artificial boosting the activity of the specific counteracting phosphatase Glc7 in vivo, which relieved the toxicity. These findings reveal a novel mechanism by which a pathogenic bacterium manipulates host cells.


Successful Resection of a Large Rectal Adenoma Using the Transsacral Approach.
The transsacral approach is not routinely used for treating rectal tumors. We report the case of a 65-year-old man with a large adenoma at the posterior wall of the mid-rectum who was treated via the transsacral approach. The same lesion had been treated using transsacral endoscopic microsurgery 8 years previously. Moreover, 11 years previously he had undergone a laparotomy for bladder cancer, and an Indiana pouch had been constructed. Abdominal computed tomography showed that the pouch was adjacent to the rectum. Therefore, the less-invasive transsacral approach, rather than the transabdominal approach, was chosen for treatment. The lesion was successfully resected, without disturbing the pouch. Histological analysis indicated tubular adenoma, with a small focus of intramucosal adenocarcinoma, and negative margins. Thus, we achieved successful resection of mid-rectal lesions via the transsacral approach, without the morbidity associated with major laparotomy. We suggest that this procedure should be a part of a surgeon's armamentarium.


Time-dependent density functional theory for open quantum systems with unitary propagation.
We extend the Runge-Gross theorem for a very general class of open quantum systems under weak assumptions about the nature of the bath and its coupling to the system. We show that for Kohn-Sham (KS) time-dependent density functional theory, it is possible to rigorously include the effects of the environment within a bath functional in the KS potential. A Markovian bath functional inspired by the theory of nonlinear Schrödinger equations is suggested, which can be readily implemented in currently existing real-time codes. Finally, calculations on a helium model system are presented.


First detection of spotted fever group Rickettsiae in ticks in Serbia.
Ticks can transmit multiple pathogenic bacteria responsible for diseases in animals and humans such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, and spotted fever group Rickettsia sp. The current study aimed to investigate the presence of Rickettsiae in ticks collected from seven localities in Serbia. One hundred thirty-one (131) questing ticks belonging to 5 tick species (Dermacentor marginatus, Dermacentor reticulatus, Haemaphysalis punctata, Haemaphysalis Concinna, and Ixodes ricinus) were collected in 2007 and 2009. Ticks were tested by polymerase chain reaction, amplifying gltA, ompA, and 17-kd genes, and sequencing analysis, revealing the presence of Rickettsia helvetica and Rickettsia monacensis in I. ricinus ticks only (infection rates 7.7% and 15.4% for R. helvetica and R. monacensis, respectively). R. helvetica has been isolated from I. ricinus ticks and has been implicated in fatal perimyocarditis. R. monacensis was first identified in I. ricinus samples collected in Germany and has recently been implicated in human infection. The results of the current study make fundamental the need to evaluate the incidence of infection with R. helvetica and R. monacensis among the resident population.


Nursing staff perspectives of continuous remote vital signs monitoring on surgical wards: Theory elicitation for a realist evaluation.
Continuous remote monitoring (CRM) provides a novel solution to the challenges of monitoring patients' vital signs in hospital, but the results of quantitative studies have been mixed. Acceptance by staff is a crucial determinant of the success of healthcare technologies and may explain these discrepancies. Drawing on the approach of realist evaluation, this paper aims to identify theories about how, why and in what conditions nursing staff perceptions vary regarding the CRM of patients' vital signs. Multiple methods were used to elicit theories about factors likely to facilitate or impede the successful implementation of continuous remote vital signs monitoring. This included a literature review, consultation with patients and observational work conducted during a randomized controlled trial (RCT) of CRM. In addition, a priori theories developed through informal interactions with patients and ward staff during the day-to-day set-up of the trial were included. The findings suggest that the perceptions of nursing staff regarding remote monitoring can be influenced by the type of patients under their care and their previous experience of telemetry. Factors which may undermine the engagement of staff are perceived staff burden, which can be dependent on contextual factors such as staffing levels, time of day and senior staff attitudes. Staff attitudes are also likely to be influenced by patient perspectives and the utility of the devices associated with remote monitoring. The successful implementation of CRM may be dependent on staff training, research staff input and hospital culture. Theories regarding nursing staff engagement with remote monitoring are numerous, varied and contradictory. The theories elicited in this initial phase will be refined during interviews with the nursing staff involved with the RCT.


Risk of Tuberculosis Development in Patients with Rheumatoid Arthritis Receiving Targeted Therapy: a Prospective Single Center Cohort Study.
Patients with rheumatoid arthritis (RA) undergoing targeted therapy have a higher risk of developing tuberculosis (TB). This requires diagnosis and treatment of latent tuberculosis infection (LTBI). We aimed to evaluate whether diagnosis and treatment of LTBI in RA are effective in Korea, and to estimate the risk of TB development by calculating the incidence rate of active TB among RA patients receiving targeted therapy. We analyzed data from two prospective cohort studies of RA patients who received biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase (JAK) inhibitor. We selected new starters of targeted therapy and classified them into three groups receiving tumor necrosis factor (TNF) inhibitor, non-TNF inhibitor, and JAK inhibitor, respectively. We then compared LTBI prevalence, treatments, and active TB incidence during first-line therapy in each group. A total of 765 RA patients (574 TNF inhibitor users, 132 non-TNF inhibitor users, and 59 JAK inhibitor users) were included in this study. Observation periods were 1,255.2 person-years (PYs), 264.7 PYs, and 53.3 PYs, respectively. All 765 patients underwent LTBI screening, and the positivity rate was 26.5% (n = 203). Of the 203 LTBI-positive patients, 189 (93.1%) received treatment. Only one patient, who was in the TNF inhibitor group, and was negative for the interferon gamma release assay (IGRA), did not receive LTBI treatment and developed active TB during follow-up. Although the prevalence of LTBI in RA patients who started targeted therapy was slightly elevated, the Korean guidelines specifying LTBI screening and treatment were effective in preventing latent TB from becoming active.


Synthesis of yttria-based crystalline and lamellar nanostructures and their formation mechanism.
A nonaqueous synthetic route for the preparation of a regular crystalline yttria mesostructure is presented. The reaction between yttrium alkoxides and benzyl alcohol results in the formation of a highly ordered lamellar nanocomposite consisting of yttria layers with a confined thickness of about 0.6 nm, separated from each other by organic layers of intercalated benzoate molecules. Doping with europium leads to strong red luminescence. The nanostructure formation proceeds via two reactions. A C--C bond formation occurs between benzyl alcohol and the isopropanolate ligand. At the same time, yttrium oxide catalyzes two low-temperature hydride-transfer reactions to form benzoic acid and toluene from benzyl alcohol via benzaldehyde, thus limiting the growth of the thickness of the lamellae.


Pilomatricoma--a reprospective analysis of 18 cases.
Pilomatricoma (calcifying epithelioma of Malherebe) is an uncommon skin tumour that occurs predominantly in young people. No studies are available from the Indian subcontinent on pilomatricoma. We analyzed records of 18 cases of pilomatricoma seen during 5 years period (1995-99). There were 16 females and 2 males and their age ranged from 5 to 60 years. All patients had solitary lesions in 10 out of 18 cases (55.5%), the tumour was located in head and neck region including 5 cases (27%) where it involved orbital margin and eye-brow. In only 2 out of 18 cases, a clinical diagnosis of pilomatricoma was suggested. In addition to the secondary changes described in previous studies, we observed additional changes like myxoid change, oedema fluid and necrosis with karyorrhectic debris in few of these tumours. Making a clinical diagnosis of pilomatricoma can be difficult. The final confirmation is by histopathological examination only.


The expression of cell cycle regulatory proteins in oligodendroglial tumors.
Oligodendroglial tumors are mainly classified histologically into 2 types of tumors--oligodendrogliomas and oligoastrocytomas--whether the tumor includes astrocytic component or not, and these are, respectively, divided histologically into 2 different malignant groups, low-grade (WHO grade II) and high-grade or anaplastic (WHO grade III). In this study, we investigated the expression of the cell cycle-related proteins and analyzed the relationship between the labeling index (LI: the percentage of positive nuclei) of these proteins and 2 histopathological phenotypes, grade and prognosis. Forty-four specimens were examined, including 11 oligodendorogliomas (0), 5 oligoastrocytomas (OA), 18 anaplastic oligodendrogliomas (aO) and 10 anaplastic oligoastrocytomas (aOA), according to the WHO classification. Of these, 19 specimens were obtained from recurrent tumors of 8 cases. The mean LI of all the investigated proteins between O and OA, and aO and aOA showed no significant differences. The mean MIB-1 LI, pRb LI, p53 LI and p14 LI of GIII were significantly higher than GII, while the mean p27 LI of GIII was significantly lower than GII. In the recurrent cases, we noted correlations between the disease-free period and MIB-1 LI (inverse), p27 LI and p14 (inverse). Significant correlations were noted between MIB-1 LI and pRb LI, MIB-1 LI and cycD1 LI, MIB-1 LI and p27 LI (inverse), pRb LI and cycD1 LI, cycD1 LI and cdk4 LI and pRb LI and p27 LI (inverse) in the pRb/cycD1-cdk4/p27 pathway, and between MIB-1 LI and p53 LI, MIB-1 LI and p14 LI, p53 LI and p14 LI, p53 LI and MDM2 LI and MDM2 LI and p14 LI in the p53/MDM2/p14 pathway. In conclusion, both pRb/cycD1-cdk4/p27 and p53/N4DM2/p14 pathways correlate with malignant progression, and MIB-1 LI, pRb LI, p27 LI, p53 LI and p14 LI reflect the histopathological malignancy of oligodendroglial tumors. MIB-1 LI, pRb LI and p27 LI are especially useful as indicators of malignancy of oligodendroglial tumors.


Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr286 in squamous cell carcinoma.
Differentiation-inducing factors (DIFs) are morphogens which induce cell differentiation in Dictyostelium. We reported that DIF-1 and DIF-3 inhibit proliferation and induce differentiation in mammalian cells. In this study, we investigated the effect of DIF-1 on oral squamous cell carcinoma cell lines NA and SAS, well differentiated and poorly differentiated cell lines, respectively. Although DIF-1 did not induce the expression of cell differentiation makers in these cell lines, it inhibited the proliferation of NA and SAS in a dose-dependent manner by restricting the cell cycle in the G0/G1 phase. DIF-1 induced cyclin D1 degradation, but this effect was prevented by treatment with lithium chloride and SB216763, the inhibitors of glycogen synthase kinase-3beta (GSK-3beta). Depletion of endogenous GSK-3beta by RNA interference also attenuated the effect of DIF-1 on cyclin D1 degradation. Therefore, we investigated the effect of DIF-1 on GSK-3beta and found that DIF-1 dephosphorylated GSK-3beta on Ser9 and induced the nuclear translocation of GSK-3beta, suggesting that DIF-1 activated GSK-3beta. Then, we examined the effect of DIF-1 on cyclin D1 mutants (Thr286Ala, Thr288Ala, and Thr286/288Ala). We revealed that Thr286Ala and Thr286/288Ala mutants were highly resistant to DIF-1-induced degradation compared with wild-type cyclin D1, indicating that the phosphorylation of Thr286 was critical for cyclin D1 degradation induced by DIF-1. These results suggest that DIF-1 induces degradation of cyclin D1 through the GSK-3beta-mediated phosphorylation of Thr286.


Management of Chordoma and Chondrosarcoma with Fractionated Stereotactic Radiotherapy.
To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for chordoma and chondrosarcoma. Twenty consecutive patients with a histopathologic diagnosis of chordoma (n = 16) or chondrosarcoma (n = 4) treated between 2010 and 2016 were retrospectively identified. All patients underwent FSRT in five fractions to a median dose of 37.5 Gy (range: 25-40 Gy) and followed with serial magnetic resonance imaging. Overall survival (OS), local recurrence-free survival (LRFS), and event-free survival (EFS) were estimated using the Kaplan-Meier method. With a median follow-up of 28 months after FSRT and 40 months after initial surgery, crude OS and LRFS were 90%. Nine patients (45%) reported grade 1-3 acute toxicity, and two patients (10%) experienced grade 4, 5 late toxicity. One patient previously treated with proton therapy died from radiation vasculopathy 9 months after FSRT. The use of FSRT for recurrent disease or in patients with prior radiation therapy was associated with significantly decreased EFS. FSRT for chordoma and chondrosarcoma is associated with high rates of OS and local control. Although many patients experience acute toxicity, there is a low incidence of late toxicity or irreversible treatment related morbidity despite the frequency of prior radiotherapy in this population. FSRT is an effective adjuvant or salvage treatment for chordoma and chondrosarcoma.


Role of PI3K/AKT/mTOR signaling pathway and sirtuin genes in chronic obstructive pulmonary disease development.
Chronic obstructive pulmonary disease (COPD) is a multifactorial disease of the respiratory system which develops as a result of a complex interaction of genetic and environmental factors closely related to lifestyle. We aimed to assess the combined effect of the PI3K/AKT/mTOR signaling pathway (PIK3R1, AKT1, MTOR, PTEN) and sirtuin (SIRT1, SIRT3, SIRT6) genes to COPD risk. SNPs of SIRT1 (rs3758391, rs3818292), SIRT3 (rs3782116, rs536715), SIRT6 (rs107251), AKT1 (rs2494732), PIK3R1 (rs10515070, rs831125, rs3730089), MTOR (rs2295080, rs2536), PTEN (rs701848, rs2735343) genes were genotyped by real-time polymerase chain reaction (PCR) among 1245 case and control samples. Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and smoking pack-years. Significant associations with COPD were identified for SIRT1 (rs3818292) (P = 0.001, OR = 1.51 for AG), SIRT3 (rs3782116) (P = 0.0055, OR = 0.69) and SIRT3 (rs536715) (P = 0.00001, OR = 0.50) under the dominant model, SIRT6 (rs107251) (P = 0.00001, OR = 0.55 for СT), PIK3R1: (rs10515070 (P = 0.0023, OR = 1.47 for AT), rs831125 (P = 0.00001, OR = 2.28 for AG), rs3730089 (P = 0.0007, OR = 1.73 for GG)), PTEN: (rs701848 (P = 0.0015, OR = 1.35 under the log-additive model), and rs2735343 (P = 0.0001, OR = 1.64 for GC)). A significant genotype-dependent variation of lung function parameters was observed for SIRT1 (rs3818292), SIRT3 (rs3782116), PIK3R1 (rs3730089), and MTOR (rs2536). Gene-gene combinations that remained significantly associated with COPD were obtained; the highest risk of COPD was conferred by a combination of G allele of the PIK3R1 (rs831125) gene and GG of SIRT3 (rs536715) (OR = 3.45). The obtained results of polygenic analysis indicate the interaction of genes encoding sirtuins SIRT3, SIRT2, SIRT6 and PI3KR1, PTEN, MTOR and confirm the functional relationship between sirtuins and the PI3K/AKT/mTOR signaling pathway.


Demonstration of pH imaging in acute stroke with endogenous ratiometric chemical exchange saturation transfer magnetic resonance imaging at 2 ppm.
pH change is often considered a hallmark of metabolic disruption in diseases such as ischemic stroke and cancer. Chemical exchange saturation transfer (CEST) MRI, particularly amide proton transfer (APT), has emerged as a noninvasive pH imaging approach. However, there are changes in multipool CEST effects besides APT MRI. Our study investigated radiofrequency (RF) amplitude-based ratiometric CEST pH imaging in acute stroke. Briefly, adult male Wistar rats underwent CEST MRI under two RF saturation (B1 ) levels of 0.75 and 1.5 μT following middle cerebral artery occlusion. Magnetization transfer (MT), direct water saturation, CEST at 2 ppm (CEST@2 ppm), amine (2.75 ppm), and APT (3.5 ppm) effects were resolved with the multipool Lorentzian fitting approach. The ratiometric analysis was measured in the ischemic lesion and the contralateral normal area, which was also correlated with pH-specific MT and the relaxation normalized APT (MRAPT) index. MT, amine CEST effect, and their respective ratiometric indices did not show significant changes in ischemic regions (p > 0.05), as expected. Whereas APT decreased in the ischemic lesion for B1 of 1.5 μT (p < 0.01), the correlation between the amide ratio with MRAPT index was moderate (r = 0.52, p = 0.02). By comparison, the ischemic tissue showed a significantly increased CEST@2 ppm for both saturation levels from the contralateral normal area (p ≤ 0.01). Importantly, the CEST@2 ppm ratio decreased in the ischemic lesion (p < 0.01), which highly correlated with the MRAPT index (r = 0.93, p < 0.001). To summarize, our study demonstrated the feasibility of endogenous CEST@2 ppm ratiometric imaging of pH upon acute stroke, promising to detect pH changes in metabolic diseases.


Steroidogenesis in the NCI-H295 Cell Line Model is Strongly Affected By Culture Conditions and Substrain.
NCI-H295 cells are the most widely used model for adrenal steroidogenesis and adrenocortical carcinoma and have been used for decades in laboratories worldwide. However, reported steroidogenic properties differ considerably. To evaluate heterogeneity of steroidogenesis among NCI-H295 cell strains, clarify the influence of culture media and test response to inhibitors of steroidogenesis by using liquid chromatography tandem mass spectrometry (LC-MS/MS). NCI-H295 cells were obtained from two cell banks and cultivated in different media. An LC-MS/MS-based panel analysis of thirteen steroids was adapted for cell culture supernatant. Cells were treated with metyrapone, abiraterone and mitotane. Mineralocorticoid synthesis was strongly affected by passaging as reflected by reduction of aldosterone secretion from 0.158±0.006 to 0.017±0.001 µg/106 cells (p<0.05). Relevant differences were also found for cells from two vendors in terms of aldosterone secretion (0.180±0.001 vs. 0.09±0.002 µg/106 cells, p<0.05). Selection of medium strongly impacted on cortisol secretion with>4-fold difference (40.6±5.5 vs. 182.1±23 µg/106 cells) and reflected differential activation of the glucocorticoid pathway. Exposure to abiraterone, metyrapone and mitotane resulted in characteristic steroidogenic profiles consistent with known mechanism of drug action with considerable differences in metabolites upstream of the blocked enzyme. We demonstrate that steroid hormone secretion in NCI-H295 cells is strongly affected by the individual strain, passage and growing conditions. These factors should be taken into account in the evaluation of experiments analyzing steroid parameters directly or as surrogate parameters of cell viability.


The uterine length in women with Turner syndrome reflects the postmenarcheal daily estrogen dose.
To evaluate the effects of estrogen substitution on the uterine development in patients with Turner syndrome. 57 women, aged 18.1-41.5 years, were treated with estrogen from puberty induction. In 21 women (37%), the uterus developed to >65 mm in length. The daily estrogen dose correlated with both uterine length (r = 0.29; p < 0.05) and Tanner breast stage (r = 0.44; p < 0.001). A negative correlation between age at artificial menarche and uterine length was found (r = -0.29; p < 0.05). The endometrium thickness was greater in women with an uterus length >65 mm (p < 0.05). In 50% of the women (18 were evaluated), an adult-shaped uterus developed. Previous growth hormone therapy (n = 32) had no impact on the uterus length. The uterine development was suboptimal in most patients. Further investigation is needed to optimize estrogen therapy for uterine development in patients with Turner syndrome.


Paclitaxel-carboplatin plus bevacizumab therapy for advanced neuroendocrine carcinoma of the uterine cervix: A retrospective case series.
There is no conclusive data on the prognosis of patients who receive paclitaxel-carboplatin (TC) plus bevacizumab therapy for advanced neuroendocrine carcinoma (NEC) of the uterine cervix, a rare histological subtype of cervical cancer. Thus, the aim of this study was to determine the efficacy of TC chemotherapy plus bevacizumab and bevacizumab single maintenance therapy for advanced NEC of the cervix. This was a retrospective review of patients who received TC plus bevacizumab therapy for metastatic, recurrent, or persistent NEC of the cervix at seven institutions between 2015 and 2020. Relevant data were extracted from the patients' medical records and analyzed. Seven patients, including six with small-cell NEC and one with large-cell NEC, were included for analysis. Three patients received bevacizumab single maintenance therapy following TC plus bevacizumab therapy, whereas four patients did not receive bevacizumab single maintenance therapy. The median overall survival and progression-free survival of the patients who received bevacizumab single maintenance therapy were longer than those of the patients who did not receive the therapy (34 months vs. 10.5 months and 19 months vs. 5 months, respectively). However, the patients who received bevacizumab single maintenance therapy had received cisplatin-based chemotherapy previously. On the premise that cisplatin-based chemotherapy is administered as the first-line treatment for advanced NEC of the cervix, bevacizumab single maintenance therapy following TC plus bevacizumab may be considered the second- or third-line treatment. However, the risk of adverse events, such as intestinal perforation, should be discussed with patients.


Microarray and quantitative PCR analysis of gene expression profiles in response to treatment with tomato leaf extract in mcf-7 breast cancer cells.
We previously found cytotoxic effects of tomato leaf extract (TLE) on the MCF-7 breast cancer cell line. The aim of this study was to ascertain the molecular mechanisms associated with the usage of TLE as an anticancer agent by microarray analysis using mRNA from MCF-7 breast cancer cells after treatment with TLE for 1 hr and 48 hrs. Approximately 991 genes out of the 30,000 genes in the human genome were significantly (p<0.05) changed after the treatment. Within this gene set, 88 were significantly changed between the TLE treated cells and the untreated MCF-7 cells (control cells) with a cut-off fold change >2.00. In order to focus on genes that were involved in cancer cell growth, only twenty-nine genes were selected, either down-regulated or up-regulated after treatment with TLE. Microarray assay results were confirmed by analyzing 10 of the most up and down regulated genes related to cancer cells progression using real-time PCR. Treatment with TLE induced significant up-regulation in the expression of the CRYAB, PIM1, BTG1, CYR61, HIF1-α and CEBP-β genes after 1 hr and 48 hrs, whereas the TXNIP and THBS1 genes were up-regulated after 1 hr of treatment but down-regulated after 48 hrs. In addition both the HMG1L1 and HIST2H3D genes were down-regulated after 1 hr and 48 hrs of treatment. These results demonstrate the potent activity of TLE as an anticancer agent.


Awareness about medico legal aspects and Consumer Protection Act among dentists.
The practice of medicine in India has undergone considerable change affecting delivery of health in both positive and negative directions. As a result, there was a growing feeling that medical treatment should be made accountable and this led to doctors and dentists becoming subject to the process of law. Patients have become more aware of their right to compensation and as a consequence doctors and dentists should be knowledgeable about the laws that govern them. To assess the awareness about Medico legal aspects and Consumer Protection Act [CPA] among Dental professionals. A self-structured validated questionnaire comprising of 20 questions related to medico legal aspects and CPA was designed. A total of 450 dental professionals were surveyed from 4 prime dental institutions in Chennai, India. Of the 450 professionals that were surveyed 150 were MDS faculty, 150 were BDS faculty and 150 were PG students. The data was subjected to SPSS, version 16 and statistically analysed using Chi square test and Fisher's exact test. A- p value less than 0.05 was considered to be statistically significant. BDS faculty, MDS faculty and PG students were found to possess similar level of understanding and there was no significant difference between the groups. Knowledge was found to be equal between male and female dentists. The young practitioners were found to be more informed about CPA than the senior practitioners. It was found that most of the participants were aware of relevant Medico legal aspects, but were less aware of CPA. This study emphasises the need for education relevant to Medico legal aspects and CPA for dental professionals.


Frequent and preferential infection of Treponema denticola, Streptococcus mitis, and Streptococcus anginosus in esophageal cancers.
Multiple cancers frequently occur in the upper digestive tract. One possible explanation is that specific bacterial infection stimulates the normal epithelium to initiate inflammation and/or promotes carcinogenesis. This study was undertaken to determine which bacterial species is predominantly associated with esophageal cancer. We examined the bacterial diversity in this type of cancer and in the saliva from healthy people by using a culture-independent molecular method. Here we report the preferential and frequent infection of the oral periodontopathic spirochete Treponema denticola (T. denticola), Streptococcus mitis (S. mitis), and Streptococus anginosus (S. anginosus) in esophageal cancer from different regions of the world, and we also describe the induction of inflammatory cytokines by infection of S. anginosus and S. mitis. Our present data suggest that these three bacteria could have significant roles in the carcinogenic process of many cases of esophageal cancer by causing inflammation and by promoting the carcinogenic process, and that eradication of these three bacteria may decrease the risk of recurrence.


Genitourinary vascularized composite allotransplantation.
Genitourinary vascularized allotransplantation (GUVCA) is gaining interest as a treatment option for patients with functional and aesthetic urogenital tissue loss. Only three cases have been done worldwide and research on the implementation and feasibility of this procedure is in an elementary state. The psychosocial impact and ethical considerations with GUVCA are remote, particularly because of the intimate and personal nature of genital tissue. Though two of the three penile transplantation cases are considered successful, various unexpected factors and complications have been described alongside these successes. Treatment outcome depends on a complex combination of immunological, technical, and psychosocial components that will be different per individual case. Multidisciplinary evaluation and treatment protocols should be established to ensure that the quality of life in GUVCA recipients can be increased in a safe and ethical way. Penile transplantation represents challenging new potential to improve phallus reconstruction in patients with severe genital tissue defects, but worldwide experience with GUVCA is limited. Controlled multicenter research is required to better define the risk/benefit ratio of this experimental yet promising treatment option.


Approach to suspected donor-derived infections.
Prevention of donor-derived disease among pediatric solid organ transplant recipients requires judicious risk-benefit assessment. Comprehensive guidelines outline specific donor risk factors and post-transplant monitoring strategies to prevent and mitigate transmission of HIV, hepatitis B, and hepatitis C. However, elimination of unanticipated donor-derived infections remains challenging. The objectives of this review are to (1) define risk of anticipated vs. unanticipated disease transmission events in pediatric solid organ transplant recipients; (2) discuss donor presentations that confer greater risk of unanticipated disease transmission; (3) develop a matrix for consideration of donor acceptance; and (4) discuss limitations and future directions for donor screening. Although solid organ transplant confers inherent risk of infection transmission, the risk of significant disease transmission events may be mitigated by a comprehensive approach including donor assessment, consideration of recipient need, post-transplant monitoring, and early intervention.


Urate transport capacity of glucose transporter 9 and urate transporter 1 in cartilage chondrocytes.
Chronic gouty arthritis, caused by a persistent increase in, and the deposition of, soluble uric acid (sUA), can induce pathological chondrocyte destruction; however, the effects of urate transport and intracellular sUA on chondrocyte functionality and viability are yet to be fully determined. Thus, the aim of the present study was to investigate the presence and functionality of a urate transport system in chondrocytes. The expression profiles of two primary urate reabsorptive transporters, glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), in human articular cartilage and chondrocyte cell lines were examined via western blotting, reverse transcription‑quantitative PCR, immunohistochemistry and immunofluorescence. Then, chondrocytes were incubated with exogenous sUA at increasing concentrations. Negative control assays were conducted via the specific knockdown of GLUT9 and URAT1 with lentiviral short hairpin (sh)RNAs, and by pretreatment with benzbromarone, a known inhibitor of the two transporters. Intracellular UA concentrations were measured using colorimetric assays. The expression levels of GLUT9 and URAT1 were determined in cartilage tissues and chondrocyte cell lines. Incubation of chondrocytes with sUA led to a concentration‑dependent increase in intracellular urate concentrations, which was inhibited by GLUT9 or URAT1 knockdown, or by benzbromarone pretreatment (27.13±2.70, 44.22±2.34 and 58.46±2.32% reduction, respectively). In particular, benzbromarone further decreased the already‑reduced intracellular UA concentrations in HC‑shGLUT9 and HC‑shURAT1 cells by 46.79±2.46 and 39.79±2.22%, respectively. Cells overexpressing GLUT9 and URAT1 were used as the positive cell control, which showed increased intracellular UA concentrations that could be reversed by treatment with benzbromarone. In conclusion, chondrocytes may possess an active UA transport system. GLUT9 and URAT1 functioned synergistically to transport UA into the chondrocyte cytoplasm, which was inhibited by specific gene knockdowns and drug‑induced inhibition. These results may be fundamental in the further investigation of the pathological changes to chondrocytes induced by sUA during gouty arthritis, and identified UA transport processes as potential targets for the early control of chronic gouty arthritis.


Antibodies to histones H1 and H5 in sera of patients with juvenile rheumatoid arthritis.
The specificity of juvenile rheumatoid arthritis (JRA) sera for histone subclasses was examined by immunoblotting. Antibodies to H1 alone were found in 4 of 21 pauciarticular-onset JRA sera, 4 of 19 polyarticular-onset JRA sera, and 2 of 11 systemic-onset JRA sera. Antibodies to H5 alone were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and 3 of 11 systemic JRA sera. Antibodies to both H1 and H5 were found in 4 of 21 pauciarticular JRA sera, 4 of 19 polyarticular JRA sera, and 1 of 11 systemic JRA sera. Antibodies to the core histones (H2A and H2B) were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and no systemic JRA sera. No reactivity to histones was observed in 30 sera from age-matched children with nonrheumatic diseases. The presence of H1 and H5 antibodies did not correlate with antinuclear antibody titers or with a homogeneous pattern of immunofluorescence. The predominance of H1 and H5 antibodies and relative absence of antibodies binding to core histones in JRA contrast with findings in adult systemic lupus erythematosus. Further, the presence of antibodies to H5 alone in some of the JRA patients indicates that the immune response in these patients is directed to determinants that are not shared by sequences of mammalian proteins.


Occupational asthma risk from exposures to toluene diisocyanate: A review and risk assessment.
Toluene Diisocyanate (TDI) is a known respiratory sensitizer linked to occupational asthma (OA). To better manage worker risks, an appropriate characterization of the TDI-OA dose-risk relationship is needed. The literature was reviewed for data suitable for dose-response modeling. Previous study data were fit to models to derive prospective occupational exposure limits (OELs), using benchmark dose (BMD) and low-dose extrapolation approaches. Data on eight TDI-exposed populations were suitable for analysis. There were 118 OA cases in a population contributing 13 590 person-years. The BMD-based OEL was 0.4 ppb. The OEL based on low-dose extrapolation to working lifetime extra risk of 1/1000 was 0.3 ppb. This study synthesized epidemiologic data to characterize the TDI-OA dose-risk relationship. This approach yielded prospective OEL estimates below recent recommendations by the American Conference of Governmental Industrial Hygienists, but given significant study limitations, this should be interpreted with caution. Confirmatory research is needed.


Deficiency of growth hormone receptor does not affect male reproduction in dwarf chickens.
Sex-linked dwarf chickens caused by the mutation of the growth hormone receptor gene are characterized by normal growth hormone (GH), very low insulin-like growth factor I (IGF-I) level in the blood, and reduced growth. It has been demonstrated that the sex-linked dwarfing gene has negative effects on female reproduction. In the current study, dwarf cocks and their phenotypic normal siblings were used to investigate the effects of dwarf gene on male reproduction. Dwarf cocks grew slower than the normal cocks did, and at 20 wk of age, their BW were 36.4% smaller. However, all parameters for semen quality, including volume, sperm concentration, viability, mobility, pH, and percentage of abnormal sperms, examined at 30 wk of age showed no significant difference between normal and dwarf cocks. The fertility of dwarf cocks was 95.2%, and the normal was 92.4%. The concentrations of GH and IGF-I in serum and seminal plasma were measured with RIA and ELISA, respectively. The serum GH in the dwarf cocks was significantly higher than their normal siblings (P < 0.05), whereas the serum IGF-I in the dwarf cocks was very low. However, the concentration of seminal IGF-I in dwarf cocks was similar to that of their normal siblings, indicating that IGF-I might be produced and acted independently in testis. In conclusion, the deficiency in GH receptor did not affect the male reproduction in dwarf chickens, and the fertility of dwarf cocks could be satisfactory for production when artificial insemination was adopted.


[Attention to the use of oral anti-diabetic medication in older adults with type 2 diabetes].
The increase proportion of older persons is continuously growing in worldwide, especially in Japan. Subsequently, the number of older adults with type 2 diabetes is also increasing. Older adults with diabetes are at substantial risk of frailty, cognitive impairment, and physical disability. They are also at greater risk for polypharmacy, depression, urinary incontinence, injurious fall, and persistent pain. Thus, older patients are a very heterogenous group of individuals. Hypoglycemia is a frequent adverse effect of treatment with sulfonylurea, glinides, or insulin in older adults with diabetes. In this review, we describe the efficacy and safety of some anti-diabetic oral agents used in older adults with type 2 diabetes, including an incretin-based drug dipeptidyl peptidase 4(DPP4) inhibitors.


[Management of a patient with critical limb ischemia].
The severity of the prognostic of critical limb ischemia imposes a multidisciplinary approach, done by a highly specialised centre. A delay in managing this condition increases significantly the risk of amputation. For most patients, a revascularisation procedure, surgical or endovascular, can be considered, since the aim of the treatment is to restore an arterial flux to permit cicatrisation and relieve pain. When the choice is possible, endovascular techniques are preferred, because more simple, done without anaesthesia and charged of less complications rate. The choice between two techniques is never simple and imposes the intervention of a multidisciplinary staff composed by vascular specialist, vascular surgeons and interventional radiologists. The aim of the medical treatment, waiting for the revascularisation, is to control the pain and the infection, prevent progression of the lesions and to optimise respiratory and cardiac functions.


Fax/modem board communications decrease preceptor communication costs.
Mail and the telephone are common communication links between departments of family medicine and their community-based preceptors. The availability of low-cost fax/modem boards offers the potential for new communication methods. This study compares the cost of personal computer-based fax/modem board communications with traditional mail and telephone linkages. The department's community preceptor faculty served as the study population. Sixty-eight physicians (54%) had fax machines; these physicians received faxes instead of mailed communications. The remaining 59 physicians (46%) received mailed communications. All preceptors received standard telephone calls. Costs for telephone, mail, and fax/modem board communications were tracked over a 4-month period. Faxes were significantly less expensive and more efficient than either telephone or mail communications. Telephone communications were the most expensive. The study suggests that fax/modem boards offer a communication linkage with preceptors that is more economical than either mail or telephone.


Screening of periodontitis-related diagnostic biomarkers based on weighted gene correlation network analysis and machine algorithms.
Periodontitis is a common oral immune inflammatory disease and early detection plays an important role in its prevention and progression. However, there are no accurate biomarkers for early diagnosis. This study screened periodontitis-related diagnostic biomarkers based on weighted gene correlation network analysis and machine algorithms. Transcriptome data and sample information of periodontitis and normal samples were obtained from the Gene Expression Omnibus (GEO) database, and key genes of disease-related modules were obtained by bioinformatics. The key genes were subjected to Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and 5 machine algorithms: Logistic Regression (LR), Random Forest (RF), Gradient Boosting Decisio Tree (GBDT), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM). Expression and correlation analysis were performed after screening the optimal model and diagnostic biomarkers. A total of 47 candidate genes were obtained, and the LR model had the best diagnostic efficiency. The COL15A1, ICAM2, SLC15A2, and PIP5K1B were diagnostic biomarkers for periodontitis, and all of which were upregulated in periodontitis samples. In addition, the high expression of periodontitis biomarkers promotes positive function with immune cells. COL15A1, ICAM2, SLC15A2 and PIP5K1B are potential diagnostic biomarkers of periodontitis.


Investigation of Exciton Recombination Zone in Quantum Dot Light-Emitting Diodes Using a Fluorescent Probe.
Exciton recombination zone, where the photons are generated, can greatly affect the performance, such as the efficiency and color purity, of the quantum dot (QD) light-emitting diodes (QLEDs). To probe the exciton recombination zone, 4-(dicyanomethylene)-2-t-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) is doped into the charge transport layer as a fluorescent sensor; by monitoring the Förster resonant energy transfer (FRET) between QD and DCJTB, the location of the recombination zone can be determined. It is found that the electron transport layer (ETL) has a great impact on the recombination zone. For example, in QLEDs with ZnMgO ETL, the recombination zone is near the interface of the QD/hole transport layer (HTL) and is shifted to the interface of the QD/ETL as the driving voltage is increased, whereas in devices with 1,3,5-tris(2-N-phenylbenzimidazolyl) benzene (TPBi) ETL, the recombination zone is close to the interface of the QD/ETL and moved to the interface of the QD/HTL with the increase in the driving voltage. Our results can also clarify the light emission mechanism in QLEDs. In devices with ZnMgO ETL, the emission is dominated by the direct charge recombination, whereas in devices with TPBi ETL, the emission is contributed by both FRET and direct charge recombination. Our studies suggest that fluorescent probe can be a powerful tool for investigating the exciton recombination zone, light emission mechanism, and other fundamental processes in QLEDs.


Why is there a gap in self-rated health among people with hypertension? A decomposition of determinants and rural-urban differences.
Hypertension affects over one billion people globally and is one of the leading causes of premature death. The low- and middle-income countries, especially the sub-Saharan Africa region, bear a disproportionately higher share of hypertension globally. Recent evidence shows a steady shift in the burden of hypertension from the more affluent and urban population towards the poorer and rural communities. Our study examined inequalities in self-rated health among people with hypertension and whether there is a rural-urban gap in the health of these patients. We then quantified factors driving the health gap. We also examined how much HIV accounts for differences in self-rated health among hypertension patients due to the relationship between HIV, hypertension and health in sub-Saharan Africa. We utilized the Zambia Household Health Expenditure and Utilization Survey for the data on SRH and other demographic and socioeconomic controls. District HIV prevalence information was from a previous study. The linear probability model provided a preliminary assessment of the association between self-rated health and independent variables. We then used the Blinder-Oaxaca decomposition to identify self-rated health inequality between urban and rural patients and determine determinants of the health gap between the two groups. Advanced age, lower education and low district HIV prevalence were significantly associated with poor health rating among hypertension patients. The decomposition analysis indicated that 45.5% of urban patients and 36.9% of rural patients reported good self-rated health, representing a statistically significant health gap of 8.6%. Most of the identified health gap can be attributed to endowment effects, with education (62%), district HIV prevalence (26%) and household expenditure (12%) being the most important determinants that explain the health gap. Urban hypertension patients have better SRH than rural patients in Zambia. Educational interventions, financial protection schemes and strengthening hypertension health services in rural areas can significantly reduce the health gap between the two regions.


The epilepsy, the protease inhibitor and the dodecamer: progressive myoclonus epilepsy, cystatin b and a 12-mer repeat expansion.
Progressive myoclonus epilepsy 1 (EPM1) or Unverricht-Lundborg disease is a human autosomal recessive neurodegenerative disorder caused by mutations in cystatin B (CSTB). The CSTB gene maps to human chromosome 21 and encodes an inhibitor of lysosomal cysteine proteases. Five point mutations have been found, two of which are seen in numerous unrelated patients. However, the main CSTB mutation in EPM1, even among patients of different ethnic origins, is an expansion of a dodecamer repeat (CCCCGCCCCGCG) in the 5' flanking area of CSTB. Most normal alleles contain either two or three repeats, while rarer normal alleles that are highly unstable contain between 12 and 17 repeats. Mutant expanded alleles have been reported to contain between 30 and 80 copies and are also highly unstable, particularly via parental transmission. There is no apparent correlation between mutant repeat length and disease phenotype. While the repeat expansion is outside the CSTB transcriptional unit, it results in a marked decrease in CSTB expression, at least in certain cell types in vitro. CSTB homozygous knockout mice show some parallels to the phenotype of human EPM1 including myoclonic seizures, development of ataxia and neuropathological changes associated with cell loss via apoptosis. Loss of CSTB function due to mutations is consistent with the observed neurodegenerative pathology and phenotype, but the functional link to the epileptic phenotype of EPM1 remains largely unknown.