The role of human urotensin-II in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a genetic condition with the hallmark feature of left ventricular hypertrophy. Human Urotensin-II (hUT-II) is regarded as a cardiovascular autacoid/hormone, and it has cardiac inotropic and hypertrophic properties. Aims of this study were to elucidate the clinical significance of serum hUT-II levels as a potential new biomarker in patients with HCM. This study included 40 HCM patients (60% males and 40% females) and were compared to 30 healthy control subjects (47% males and 53% females. All patients underwent extensive clinical, laboratory, and echocardiographic. Blood samples were taken to test for serum hUT-II levels by commercial ELISA Kit. Serum hUT-II was significantly higher (p < 0.01) in patients with HCM (15.8 ± 2.1 pmol/L) compared with healthy controls (3.3 ± 1.7 pmol/L). With regard to HCM patient, Serum hUT-II levels were significantly higher in the female with 16.3 ± 1.9 pmol/L than the male with 15.4 ± 2.2 pmol/L (p < 0.05). Among echocardiographic parameters, hUT-II was negatively associated with ejection fraction (r = -0.160, p = 0.324). Results of the first study indicated that serum hUT-II levels were markedly elevated in patients with HCM. Serum hUT-II is a novel biomarker parameter that has clinical use in patients with the severity of LVH.


Vascularization of the adrenal cortex: its possible involvement in the regulation of steroid hormone release.
This review examines the morphology of the adrenal gland with particular reference to the adrenal vasculature. It examines the possibility that variability in adrenal gland responsiveness may be attributable to neural or hormonal modulation of adrenal blood flow. Changes in the rate of blood flow through the adrenal cortex would be expected to play an important role in the regulation of steroid hormone release. It would affect both the delivery of the major stimulant (ACTH) and the removal of the end product from the steroidogenic cells (the glucocorticoids). In the past, interest in this area has concentrated on the regulation of arterial blood flow, rather than the regulation of venous drainage. The current review examines the concept of vascular damming, and attempts to link the morphological features of the gland with experimental data associated with glucocorticoid release. It is postulated that regulation of venous drainage, via the vascular dam, plays an important role in the storage of the secretory product during the animals' inactive phase, and in the initial rapid rise in plasma levels of the glucocorticoids seen in response to stress or injection of ACTH.


Radiological features of rare non-odontogenic lesions of the jaws.
The jaws can be affected by several lesions that manifest in the oral cavity, but little is known about non-odontogenic benign and malignant lesions and their radiological findings. Our aim was to discuss the imaging findings of non-odontogenic jaw lesions to help the surgeon in the diagnosis and formulating a differential diagnosis for this vast spectrum of jaw lesions with overlapping clinical and imaging appearances. CT and MR images of the mandible, maxillofacial region, and neck were retrieved from the archive of the Radiology Department of Pamukkale University for the duration between 2012-2023 and assessed. A total of 8125 CT and MR images were retrospectively analyzed. The mean age of the patients was 39.5 years in females and 43.2 in males, with a range varying from 15 to 72 years. Histopathologically approved benign and malignant non-odontogenic lesions were detected in only 19 patients out of 8125 images (0.23%). Osteomyelitis and abscess were the most common (n=3; 0.03%), followed by two cases (n=2; 0.02%) of each fibrous dysplasia, hemangioma, osteosarcoma, squamous cell carcinoma, and multiple myeloma, and one case (n=1; 0.01%) of each ossifying fibroma, osteoma, lymphoma, metastasis, and solitary bone cyst. Although non-odontogenic benign and malignant lesions of the jaw are rare, awareness of the radiological features of these lesions plays an important role in their diagnosis and management.


Assessing the causal role of epigenetic clocks in the development of multiple cancers: a Mendelian randomization study.
Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker. We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach. Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04-1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09-1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97-1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers. GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks and cancers were inconsistent. Further work is required to investigate the potential mechanisms underlying the results. FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z which is part of grant 218495/Z/19/Z). KKT was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and by the Hellenic Republic's Operational Programme 'Competitiveness, Entrepreneurship & Innovation' (OΠΣ 5047228). PH was supported by Cancer Research UK (C18281/A29019). RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. GDS and CLR were supported by the Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5, respectively) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). REM was supported by an Alzheimer's Society project grant (AS-PG-19b-010) and NIH grant (U01 AG-18-018, PI: Steve Horvath). RCR is a de Pass Vice Chancellor's Research Fellow at the University of Bristol.


Human dermal stem/progenitor cell-derived conditioned medium ameliorates ultraviolet a-induced damage of normal human dermal fibroblasts.
Adult skin stem cells are considered an attractive cell resource for therapeutic potential in aged skin. We previously reported that multipotent human dermal stem/progenitor cells (hDSPCs) can be enriched from (normal human dermal fibroblasts (NHDFs) using collagen type IV. However, the beneficial effects of hDSPCs on aged skin remain to be elucidated. In the present study, we analyzed the growth factors secreted from hDSPCs in conditioned medium (CM) derived from hDSPCs (hDSPC-CM) and found that hDSPCs secreted higher levels of bFGF, IGFBP-1, IGFBP-2, HGF, VEGF and IGF-1 compared with non-hDSPCs. We then investigated whether hDSPC-CM has an effect on ultraviolet A (UVA)-irradiated NHDFs. Real-time RT-PCR analysis revealed that the treatment of UVA-irradiated NHDFs with hDSPC-CM significantly antagonized the UVA-induced up-regulation of the MMP1 and the UVA-induced down-regulation of the collagen types I, IV and V and TIMP1 mRNA expressions. Furthermore, a scratch wound healing assay showed that hDSPC-CM enhanced the migratory properties of UVA-irradiated NHDFs. hDSPC-CM also significantly reduced the number of the early and late apoptotic cell population in UVA-irradiated NHDFs. Taken together, these data suggest that hDSPC-CM can exert some beneficial effects on aged skin and may be used as a therapeutic agent to improve skin regeneration and wound healing.


Conformational Complexity in the LH2 Antenna of the Purple Sulfur Bacterium Allochromatium vinosum Revealed by Hole-Burning Spectroscopy.
This work discusses the protein conformational complexity of the B800-850 LH2 complexes from the purple sulfur bacterium Allochromatium vinosum, focusing on the spectral characteristics of the B850 chromophores. Low-temperature B850 absorption and the split B800 band shift blue and red, respectively, at elevated temperatures, revealing isosbestic points. The latter indicates the presence of two (unresolved) conformations of B850 bacteriochlorophylls (BChls), referred to as conformations 1 and 2, and two conformations of B800 BChls, denoted as B800R and B800B. The energy differences between average site energies of conformations 1 and 2, and B800R and B800B are similar (∼200 cm-1), suggesting weak and strong hydrogen bonds linking two major subpopulations of BChls and the protein scaffolding. Although conformations 1 and 2 of the B850 chromophores, and B800R and B800B, exist in the ground state, selective excitation leads to 1 → 2 and B800R → B800B phototransformations. Different static inhomogeneous broadening is revealed for the lowest energy exciton states of B850 (fwhm ∼195 cm-1) and B800R (fwhm ∼140 cm-1). To describe the 5 K absorption spectrum and the above-mentioned conformations, we employ an exciton model with dichotomous protein conformation disorder. We show that both experimental data and the modeling study support a two-site model with strongly and weakly hydrogen-bonded B850 and B800 BChls, which under illumination undergo conformational changes, most likely caused by proton dynamics.


Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases.
We have investigated the changing rule of serum form of GP73 (sGP73) in different hepato-pathologic processes and identified the sGP73 role in inflammation, fibrosis and carcinogenesis since sGP73 has been regarded as a candidate tumor marker. Quantitative enzyme-linked immunosorbent assay detected sGP73 in 535 subjects with hepatocellular carcinoma (HCC), liver cirrhosis (LC), hepatitis, focal nodular hyperplasia (FNH), angioma, intra-hepatic cholangio-carcinoma (ICC) and metastatic cancer from adenocarcinomas (MC). Median sGP73 in LC was higher than in HCC and hepatitis (p = 0.001), and sGP73 in all three groups were higher than those in healthy individuals (p < 0.001); sGP73 in LC patients with Child-Pugh class A was lower than in class B and C (p = 0.001), no significant difference was found between early and advanced HCC groups (110.4 μg/L vs. 102.8 μg/L). AFP/GP73 had a sensitivity of 75.8% and specificity of 79.7% with an area under the receiver operating curve (AUROC) of 0.844 vs. 0.812 for AFP (p = 0.055) with a sensitivity of 95.2% and specificity of 47.1%; in detecting early HCC, AUROC of AFP/GP73 was 0. 804 vs. 0.766 for AFP (p = 0.086). sGP73 correlated with AST, AST/ALT, ALB, A/G and ALP in LC. The positive rate of sGP73 in angioma, FNH, ICC, and MC was 0, 50, 63.3, 53.3%, respectively; AFP/GP73 was 0.796 with the sensitivity of 81.4% and specificity of 70.0% when differentiating MC from AFP-negative HCC. Increased sGP73 is related to hepatic impairment and chronic fibrosis, and when combined with AFP could improve the differential diagnosis of hepatic diseases.


Convenient syntheses of 3'-amino-2',3'-dideoxynucleosides, their 5'-monophosphates, and 3'-aminoterminal oligodeoxynucleotide primers.
5'-Protected 3'-amino-2',3'-dideoxynucleosides containing any of the four canonical nucleobases (A/C/G/T) were prepared via azides in five to six steps, starting from deoxynucleosides. For pyrimidines, the synthetic route involved nucleophilic opening of anhydronucleosides. For purines, an in situ oxidation/reduction sequence, followed by a Mitsunobu reaction with diphenyl-2-pyridylphosphine and sodium azide, provided the 3'-azidonucleosides in high yield and purity. For solid-phase synthesis of aminoterminal oligonucleotides, aminonucleosides were linked to controlled pore glass through a novel hexafluoroglutaric acid linker. These supports gave 3'-aminoterminal primers in high yield and purity via conventional DNA chain assembly and one-step deprotection/release with aqueous ammonia. Primers thus prepared were successfully tested in enzyme-free chemical primer extension, an inexpensive methodology for genotyping and labeling. Protected 5'-monophosphates of 3'-amino-2',3'-dideoxynucleosides were also prepared, providing starting materials for the preparation of labeled or photolably protected monomers for chemical primer extension.


Mutations of deubiquitinase OTUD1 are associated with autoimmune disorders.
Dysregulation of innate immunity accompanied by excessive interferon production contributes to autoimmune disease. However, the mechanism by which the immune response is modulated in autoimmune disorders is largely unknown. Here we identified loss-of-function mutations of OTUD1 associated with multiple autoimmune diseases. Under inflammatory conditions, inducible OTUD1 acts as an immune checkpoint and blocks RIG-I-like receptors signaling. As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63-linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity. In contrast, OTUD1 mutants impair its suppressive effects on IRF3 via attenuating the OTUD1 deubiquinase activity or its association with IRF3. Moreover, we found FOXO3 signaling is required for OTUD1 induction upon antigenic stimulation. Our data demonstrate that OTUD1 is involved in maintaining immune homeostasis and loss-of-function mutations of OTUD1 enhance the immune response and are associated with autoimmunity.


[Expression in Escherichia coli of DNA coding for human tumor necrosis factor].
The variants of expression in Escherichia coli of artificial DNA coding for human tumor necrosis factor, an important immune modulator with selective cytotoxic action on a number of transformed cell lines have been described. The DNA was placed under control of either phage M13 promoter of gene for main coat protein or tandem of pair of E. coli tryptophane promoters. It has been shown that E. coli cells harbouring plasmids described with artificial TNF gene provide good level of protein biosynthesis. The protein has been purified by anion exchange chromatography near to homogeneity and used for preparation of monoclonals. As result three hybridomas effectively produced high affinity monoclonal anti-TNF antibodies have been obtained and characterized.


In good times and bad: p73 in cancer.
It is widely accepted in cancer biology that p53 has a tumor suppressive activity, which is lost during tumorigenesis most frequently by mutations in the p53 gene. The discovery of p73 as the first homologue of p53 raised immediate expectations about p53-like tumor suppressor activities. Although tumors show changes in the expression level of p73 and differences in the expression pattern of p73 isoforms, mutations are not commonly observed making it difficult to infer p73's role in tumorigenesis. An experimental model of human cell transformation closely mimics the expression changes observed in cancer patients and provides novel insights into the regulation and function of p73 in the various steps on the road to malignant transformation. p53-like isoforms of p73 (TAp73) are upregulated early during the transformation process in response to RB pathway alterations and block progression to the fully transformed state. Antagonists of TAp73 such as the dominant-negative p73 protein DeltaNp73 overcome this block and pave the way to full transformation. Here we review these findings in the context of patient data and recent advances on molecular aspects of p73 function and discuss the implications for p73 as a target for cancer therapy.


Design and development of highly effective Lewis acid catalysts for enantioselective Diels-Alder reactions.
This report describes the design and development of chiral Co(III)-salen catalysts for enantioselective Diels-Alder reactions. A crystal structure of a Co-salen catalyst with two equivalents of benzaldehyde provided insight on the factors that may be important for enantioselectivity. On the basis of this structural information, new catalysts were prepared in which the "bay region" tert-butyl groups were replaced by trimethylsilyl groups. The new silyl-substituted catalysts were exceptionally effective (catalyst loadings down to 0.05 mol %) and convenient to use-room temperature, under an air atmosphere, using a minimum amount of solvent.


Paranasal sinus osteoma: is there any association with anatomical variations?
Developmental disturbances of the paranasal sinuses are proposed as the cause of osteoma. We examined whether such disturbances may result in the frequent presence of anatomical variations of the paranasal sinuses in patients with osteoma. The study was performed retrospectively on 2,820 patients subjected to CT examination during 2005 - 2011. Demographic and CT characteristics of osteoma, and associated pathological findings were evaluated for 104 patients with diagnosed osteoma. The presence of anatomical variations was assessed for 51 osteoma patients with a complete medical history, and for 1,233 patients from a control group. The prevalence of osteomas was found to be 3.69%, with male to female ratio 1.08:1. The frontal sinus was most commonly affected. The presence of anatomical variations was more frequent in patients with osteoma than in controls, with significant differences confirmed for the sphenomaxillary plate, infraorbital cell, and crista galli pneumatization. The paranasal sinus osteoma is associated with higher prevalence of anatomical variations. This can be explained either by the stronger influence of genetic and/or environmental factors on the development of the paranasal sinuses in patients with osteoma, or by their higher susceptibility to above mentioned factors.


Suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice.
We have established two mouse models of central nervous system (CNS) demyelination that differ from most other available models of multiple sclerosis (MS) in that they represent a mixture of viral and immune triggers. In the first model, ocular infection of different strains of mice with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination. In the second model, depletion of macrophages causes CNS demyelination in mice that are ocularly infected with wild-type (WT) HSV-1. In the present study, we found that the demyelination in macrophage-intact mice infected with HSV-IL-2 was blocked by depletion of FoxP3-expressing cells, while concurrent depletion of macrophages restored demyelination. In contrast, demyelination was blocked in the macrophage-depleted mice infected with wild-type HSV-1 following depletion of FoxP3-expressing cells. In macrophage-depleted HSV-IL-2-infected mice, demyelination was associated with the activity of both CD4+ and CD8+ T cells, whereas in macrophage-depleted mice infected with WT HSV-1, demyelination was associated with CD4+ T cells. Macrophage depletion or infection with HSV-IL-2 caused an imbalance of T cells and TH1 responses as well as alterations in IL-12p35 and IL-12p40 but not other members of the IL-12 family or their receptors. Demyelination was blocked by adoptive transfer of macrophages that were infected with HSV-IL-12p70 or HSV-IL-12p40 but not by HSV-IL-12p35. These results indicate that suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice.


Conservative management of placenta accreta: review of three cases.
Placenta accreta occurs when the placenta is abnormally adherent to the uterus, often resulting in complications in the peripartum period such as severe haemorrhage, a possible need for caesarean hysterectomy, and even severe injuries to pelvic organs. There has been a gradual shift towards conservative management of placenta accreta, involving uterine and placental conservation, with the main aim being to reduce pelvic injury and haemostasis with the aid of intervention radiology by means of insertion of occluding balloons into the internal iliac arteries. This strategy has previously been shown to reduce morbidity and mortality in carefully selected cases of placenta accreta. We review three cases of successful uterine conservation performed in our institution.


"When I am with my husband, I do not feel mosquito bite".
Purpose The purpose of this paper is to explore how socio-cultural beliefs and practices could influence the knowledge, attitude and perception of insecticide-treated net (ITN) use in the control of malaria amongst pregnant women attending antenatal clinic. Design/methodology/approach Data were gathered using interviews and documentary review. Framework analysis was applied to classify emerging themes and the findings interpreted using the health belief model. Findings The findings showed that the pregnant women had appreciable knowledge, both the positive and negative attitudes and the perceptions of insecticide treated nets. To most of them, sleeping under an ITN would not affect pregnancy/cause abortion, but rather prevent mosquito bites and associated malaria. Research limitations/implications The limitations include the sample size of participants and health facilities used. Lack of application of a quantitative research method meant that the authors could not quantify the findings to ensure generalisation to the entire population. Practical implications The findings suggest that health policy makers, implementers and health professionals need to appreciate the perception and the attitude of pregnant women when designing policy guidelines for the malaria control programme. Social implications This paper helps to elucidate on how socio-cultural beliefs and practices could influence the knowledge, attitude and perception of ITN usage amongst both pregnant women and people in malaria endemic communities. Originality/value This paper suggests that health policy makers, implementers and health professionals have to devise strategies to address socio-cultural beliefs and practices in the scaling up of malaria control programmes.


Operative anatomy and technique of radical parametrial resection in the surgical treatment of cervical cancer.
Wertheim's radical operation aimed, by removing the parametrial tissue far from the tumour, to achieve margins free of disease. The paratissues contain the lymphatic channels draining the cervix. They run to the pelvic wall and are interspersed by lymph nodes scattered throughout the parametrium. If lymphadenectomy is to be curative then the entire parametrium must be removed. To this end the resection of the cardinal ligament was pushed to its limit by dissection directly at the pelvic wall. The surgical technique is guided by the anatomy of the pelvic fascia. The gaine hypogastrique lies just beneath the peritoneum and facilitates the opening of the paravesical space. The following are discussed: the condensations of the pelvic fascia; the composition of the cardinal ligament; the division into a venous, an arterial, and a neurovegetative root; and the anatomy of the connective tissue planes. The order in which the surgical steps are carried out is important. The paraspaces are opened first. The ureter is identified, and lymphadenectomy is performed. The rectum is dissected off the vagina, and the uterosacral ligaments are identified and removed. Only then is the vesico-uterine fold opened. The bladder is dissected off the vagina, and the anterior parametrium is clamped and divided. Now the cardinal ligament is completely exposed. The bladder, rectum and ureter have been mobilized so that the parametrium can be divided sharply directly at the pelvic wall, clipping the vessels step-by-step. The paracolpium is clamped and divided according to the proposed vaginal cuff. Thus, the entire lymphatic drainage can be removed. The value of this extension of radical abdominal hysterectomy lies especially in the treatment of large, voluminous tumours.


Ovarian mass-differentiating benign from malignant: the value of the International Ovarian Tumor Analysis ultrasound rules.
Ovarian cancer, the fifth most common cause of cancer death among women, has the highest mortality rate of all gynecologic cancers. General survival rate is <50% but can reach 90% if disease is detected early. Ultrasound is presently the best modality to differentiate between benign and malignant status. The patient with a malignant mass should be referred to an oncology surgeon since results have been shown to be superior to treatment by a specialist. Several ultrasound-based scoring systems exist for assessing the risk of an ovarian tumor to be malignant. The International Ovarian Tumor Analysis group published 2 such systems: the ultrasound Simple Rules and the Assessment of Different NEoplasias in the adneXa model. The Simple Rules classifies a tumor as benign, malignant, or indeterminate and the Assessment of Different NEoplasias in the adneXa model determines the risk for a tumor to be benign or malignant and, if malignant, the risk of various stages. Sensitivity of the Simple Rules and Assessment of Different NEoplasias in the adneXa model (using a cut-off of 10% to predict malignancy) are 92% and 96.5%, respectively, and specificities are 96% and 71.3%, respectively. These models are the best predictive tests for the preoperative classification of adnexal tumors. Their intent is to help the specialist make management decisions when faced with a patient with a persistent ovarian mass. The models are simple, are easy to use, and have been validated in multiple reports but not in the United States. We suggest they should be validated and widely introduced into medical practice in the United States.


Biochar Induces Changes to Basic Soil Properties and Bacterial Communities of Different Soils to Varying Degrees at 25 mm Rainfall: More Effective on Acidic Soils.
Biochar and chemical fertilizer have been widely used in agriculture. Most studies have proved that they not only alter soil nutrient content, but also have an impact on soil microbial communities. However, the effects of biochar and chemical fertilizer application on the overall bacterial community in different soil types under rainfall conditions are not yet understood. We took rainfall as a fixed influencing factor and selected four typical soils of China to investigate the bacterial effects of biochar and chemical fertilizer at 25 mm rainfall, and to identify specific differential bacteria and their functions, and to explore the changes of the bacterial community structure of different soil types. The depth of simulated rainfall was 25 mm each time. Yellow-brown soil, fluvo-aquic soil, lou soil, and black soil were chosen for experiment and each soil was divided into four treatments, included non-biochar and non-fertilizer (CK), fertilizer alone (F), biochar alone (C), and combination of biochar and fertilizer (FC). The results indicated that biochar and fertilizer have a more significant effect on bacterial communities in acidic soils. The amendment of biochar and fertilizer alone or together identified 3 (f_Oxalobacteraceae, f_Solibacteraceae_Subgroup_3, f_Sphingomonadaceae), 5 (f_Chitinophagaceae, f_Comamonadaceae, f_Geobacteraceae, f_norank_o_SC-I-84, f_norank_c_OPB35_soil_group), 1 (f_Blastocatellaceae_Subgroup_4) and 0 differential bacteria in yellow-brown soil, fluvo-aquic soil, lou soil, and black soil by statistical test. In yellow-brown soil, the application of biochar alone increased the relative abundance of potential pathogens within the Sphingomonadaceae and reduced the relative abundance of beneficial bacteria in Solibacteraceae, but the addition of biochar and fertilizer together increased the relative abundance of some beneficial bacteria in Oxalobacteraceae. In fluvo-aquic soil, both biochar, and chemical fertilizers promoted the relative abundance of some beneficial bacteria belonging to Chitinophagaceae, Comamonadaceae, and Geobacteraceae that may be involved in nutrient cycling, degradation of plant residues and increase of metal tolerance. The interactions between acidic soil bacterial communities and measured soil parameters including pH, organic matter were found to be statistically significant. Results from this study revealed that it is necessary to formulate biochar and fertilizer application schemes based on different soil types.


Reversible induction of phantom auditory sensations through simulated unilateral hearing loss.
Tinnitus, a phantom auditory sensation, is associated with hearing loss in most cases, but it is unclear if hearing loss causes tinnitus. Phantom auditory sensations can be induced in normal hearing listeners when they experience severe auditory deprivation such as confinement in an anechoic chamber, which can be regarded as somewhat analogous to a profound bilateral hearing loss. As this condition is relatively uncommon among tinnitus patients, induction of phantom sounds by a lesser degree of auditory deprivation could advance our understanding of the mechanisms of tinnitus. In this study, we therefore investigated the reporting of phantom sounds after continuous use of an earplug. 18 healthy volunteers with normal hearing wore a silicone earplug continuously in one ear for 7 days. The attenuation provided by the earplugs simulated a mild high-frequency hearing loss, mean attenuation increased from <10 dB at 0.25 kHz to >30 dB at 3 and 4 kHz. 14 out of 18 participants reported phantom sounds during earplug use. 11 participants presented with stable phantom sounds on day 7 and underwent tinnitus spectrum characterization with the earplug still in place. The spectra showed that the phantom sounds were perceived predominantly as high-pitched, corresponding to the frequency range most affected by the earplug. In all cases, the auditory phantom disappeared when the earplug was removed, indicating a causal relation between auditory deprivation and phantom sounds. This relation matches the predictions of our computational model of tinnitus development, which proposes a possible mechanism by which a stabilization of neuronal activity through homeostatic plasticity in the central auditory system could lead to the development of a neuronal correlate of tinnitus when auditory nerve activity is reduced due to the earplug.


Low-density lipoproteins investigated under high hydrostatic pressure by elastic incoherent neutron scattering.
Human low-density lipoprotein (LDL) is a highly complex nano-particle built up of various lipid classes and a single large protein moiety (apoB-100) owning essential physiological functions in the human body. Besides its vital role as a supplier of cholesterol and fat for peripheral tissues and cells, it is also a known key player in the formation of atherosclerosis. Due to these important roles in physiology and pathology the elucidation of structural and dynamical details is of great interest. In the current study we drew a broader picture of LDL dynamics using elastic incoherent neutron scattering (EINS) as a function of specified temperature and pressure points. We not only investigated a normolipidemic LDL sample, but also a triglyceride-rich and an oxidized one to mimic pathologic conditions as found under hyperlipidemic conditions or in atherosclerotic plaques, respectively. We could show that pressure has a significant effect on atomic motions in modified forms of LDL, whereas the normolipidemic sample seems to cope much better with high-pressure conditions irrespective of temperature. These findings might be explained by the altered lipid composition, which is either caused through elevated triglyceride content or modifications through lipid peroxidation.


Nutrient provisioning facilitates homeostasis between tsetse fly (Diptera: Glossinidae) symbionts.
Host-associated microbial interactions may involve genome complementation, driving-enhanced communal efficiency and stability. The tsetse fly (Diptera: Glossinidae), the obligate vector of African trypanosomes (Trypanosoma brucei subspp.), harbours two enteric Gammaproteobacteria symbionts: Wigglesworthia glossinidia and Sodalis glossinidius. Host coevolution has streamlined the Wigglesworthia genome to complement the exclusively sanguivorous tsetse lifestyle. Comparative genomics reveal that the Sodalis genome contains the majority of Wigglesworthia genes. This significant genomic overlap calls into question why tsetse maintains the coresidence of both symbionts and, furthermore, how symbiont homeostasis is maintained. One of the few distinctions between the Wigglesworthia and Sodalis genomes lies in thiamine biosynthesis. While Wigglesworthia can synthesize thiamine, Sodalis lacks this capability but retains a thiamine ABC transporter (tbpAthiPQ) believed to salvage thiamine. This genetic complementation may represent the early convergence of metabolic pathways that may act to retain Wigglesworthia and evade species antagonism. We show that thiamine monophosphate, the specific thiamine derivative putatively synthesized by Wigglesworthia, impacts Sodalis thiamine transporter expression, proliferation and intracellular localization. A greater understanding of tsetse symbiont interactions may generate alternative control strategies for this significant medical and agricultural pest, while also providing insight into the evolution of microbial associations within hosts.


Short communication: Correlation between within-herd antibody-prevalence and bulk tank milk antibody levels to Mycobacterium avium ssp. paratuberculosis using 2 commercial immunoassays.
The objective of this study was to determine the correlation between the results obtained with the ELISA technique for antibodies to Mycobacterium avium ssp. paratuberculosis in serum and bulk tank milk at the herd level. For this purpose, 203 samples of bulk tank milk were analyzed with 2 commercial ELISA from dairy herds with a prevalence of seropositive animals that was also determined. In regard to the reference test (results in blood serum), the sensitivity of the bulk tank milk test to detect high-positive herds (≥10% seroprevalence) ranged from 85.7 to 71.4%. The specificity to detect herds with no seropositive animals ranged from 70.5 to 53%. In a quantitative approach, Pearson correlation coefficients, reported as a measure of the linear association between herd seroprevalences and transformed optical density values recorded in bulk tank milk, were 0.39 and 0.54 for the studied ELISA. Although the test results were relatively fairly correlated with the within-herd prevalence, the practical utility of bulk tank milk testing for Mycobacterium avium ssp. paratuberculosis seems limited, especially regarding specificity.


Coincidence of Incomplete Pentalogy of Cantrell and Meningomyelocele in a Dizygotic Twin Pregnancy.
Pentalogy of Cantrell is an extremely rare and lethal syndrome. Ectopia cordis is frequently found in fetuses with POC but not required for incomplete forms. Likewise, meningomyelocele is a relatively uncommon neural tube defect affecting central nervous system and associated with neurological problems. Herein, we presented a woman with dizygotic twin pregnancy having coincidence of incomplete POC and MMC in each individual fetus, which has never been reported previously.


Kinetics and microstructure associated with nonisothermal nucleation and growth processes.
The impact of nonisothermal conditions on the kinetics and microstructure associated with a first-order phase transformation is investigated using simulation and a correlation function formalism. More specifically, equal-time correlation functions and microstructural descriptors of grain area are calculated using an N-fold Monte Carlo simulation and compared directly with their theoretical counterparts for a range of heating rates. Finally, connections between these results and those obtained experimentally via calorimetry and microscopy are discussed.


Resistance to serum bactericidal activity distinguishes Brazilian purpuric fever (BPF) case strains of Haemophilus influenzae biogroup aegyptius (H. aegyptius) from non-BPF strains. Brazilian Purpuric Fever Study Group.
We studied the ability of normal human serum to lyse H. influenzae biogroup aegyptius (H. aegyptius) isolates recovered from patients with Brazilian purpuric fever (BPF clone) or non-BPF clone strains. BPF clone isolates, although similar to non-BPF clone isolates with regard to the ability to fix C3 to their surfaces, could be distinguished from non-BPF clone strains by their resistance to lysis in vitro following incubation with normal adult human serum.


Job compensable factors and factor weights derived from job analysis data.
Government data on 1,039 job titles in Taiwan were analyzed to assess possible relationships between job attributes and compensation. For each job title, 79 specific variables in six major classes (required education and experience, aptitude, interest, work temperament, physical demands, task environment) were coded to derive the statistical predictors of wage for managers, professionals, technical, clerical, service, farm, craft, operatives, and other workers. Of the 79 variables, only 23 significantly related to pay rate were subjected to a factor and multiple regression analysis for predicting monthly wages. Given the heterogeneous nature of collected job titles, a 4-factor solution (occupational knowledge and skills, human relations skills, work schedule hardships, physical hardships) explaining 43.8% of the total variance but predicting only 23.7% of the monthly pay rate was derived. On the other hand, multiple regression with 9 job analysis items (required education, professional training, professional certificate, professional experience, coordinating, leadership and directing, demand on hearing, proportion of shift working indoors, outdoors and others, rotating shift) better predicted pay and explained 32.5% of the variance. A direct comparison of factors and subfactors of job evaluation plans indicated mental effort and responsibility (accountability) had not been measured with the current job analysis data. Cross-validation of job evaluation factors and ratings with the wage rates is required to calibrate both.


[Changes in the biochemical composition, structure, and function of pea leaf chloroplasts in iron deficiency and root anoxia].
A combined effect of iron deficiency and root anoxia on the biochemical composition, function, and structure of pea leaf chloroplasts was studied. It was found that the chlorosis of apical leaves in response to iron deficiency was determined by the reduction of light-harvesting complexes I and II. Under root anoxia, complexes of the reaction centers of photosystems I and II degraded first. Weak activity was preserved even in yellow and white leaves under the effect of both factors. The ultrastructure of leaf chloroplasts gradually degraded. Initially, intergranal thylakoid sites were reduced, and the longitudinal orientation of grana was disturbed. However, yellow and white leaves still retained small thylakoids and grana. It is concluded that the degrading effects of iron deficiency and root anoxia on the complex composition and leaf chloroplast structure and function are additive because of their autonomous mechanisms.


Altered toxicities of fatty acid salts in green paramecia cultured in different waters.
Detergents including fatty acid salts act as surface-active agents and thus possibly damage the plasma membrane structures of aquatic organisms. Therefore, when excess, the house-used and industrial outflows of such detergents into aquatic environments may have considerable impacts on the ecosystem. In this study, we propose the use of green paramecia (Paramecium bursaria) for assessing the acute toxicity of eight fatty acid salts (Na and K salts of oleate, palmitate, laurate and myristate) under various water conditions. The Paramecium in the stationary phase were used for a toxicity assay carried out on 12-well microplates and the median lethal concentration (LC50) was determined for each fatty acid salt. In the low mineral culture medium prepared with ultra-pure water, the LC50 for each fatty acid ranged from 5.8 to 144 ppm (w/v). The toxic levels of fatty acid salts differed in the following order: laurate, myristate > or = oleate, palmitate. The toxic levels of oleate and palmitate salts were ca. 10-fold lower than those of laurate and myristate salts. When river water and local tap water instead of ultra-pure water were used for culturing, the toxic levels of all fatty acid salts were drastically lowered compared to the low mineral condition by 30- to 100-fold (198-660 ppm, w/v). Similar detoxification effect was observed when Ca or Mg was added to the low mineral culture media, indicating that the toxicity of fatty acid salts can be notably lowered as the mineral content increases. As we demonstrated that toxicities of fatty acid salts can be lowered in river water and tap water compared to the low mineral condition, some chemical substances behave differently in the different water conditions. Therefore, the use of natural waters reflecting the real environmental conditions in further collection of data on the ecotoxicity impacts of variety of chemicals is highly encouraged.


Development of magnetically aligned single-walled carbon nanotubes-gelatin composite films.
Magnetically aligned and highly dispersed single-walled carbon nanotubes (SWNTs)-gelatin composite films were fabricated on a quartz substrate of newly designed disassemblable sample cells. After an SWNTs-gelatin composite sol in each sample cell was exposed to vertical DC magnetic fields to 28 T during the sol-gel transition, a side plate with a polytetrafluoroethylene film attached to the inner surface was removed from the sample cell carefully, and the composite gel left on the other side plate made of quartz was dehydrated in a nonmagnetic circumstance. We have found that the alignment of SWNTs is retained in uniform composite films obtained after the nonmagnetic drying process. Both polarized absorption measurements and polarized Raman scattering measurements were performed in order to confirm the alignment of SWNTs in the composite films consistently. The optical anisotropy of the composite films increased somewhat superlinearly as a function of the magnetic field applied during the sol-gel transition and reached to 0.13 at 28 T. The nonmagnetic drying process would make it easy to apply higher magnetic fields to the fabrication of aligned SWNTs films as it consumes resources to keep operating high field magnets such as hybrid magnets during the drying process.


Sexual Orientation Discordance and Young Adult Mental Health.
During the course of sexual development, many people experience dissonance between dimensions of sexual orientation, including attraction, behavior, and identity. This study assesses the relationship between sexual orientation discordance and mental health. Data were obtained from the National Longitudinal Study of Adolescent to Adult Health (n = 8,915; female = 54.62 %; non-Hispanic black = 18.83 %, Hispanic = 14.91 %, other race (non-white) = 10.79 %). Multivariable linear regression evaluated the correlation between sexual orientation discordance and perceived stress and depressive symptomatology. Models were stratified by sex and sexual identity. Among self-identified heterosexual females and mostly heterosexual males, sexual orientation discordance predicted significantly increased depressive symptomatology. No other subpopulation demonstrated a significant correlation between sexual orientation discordance and depressive symptomatology or perceived stress. The association between sexual orientation discordance and depressive symptomatology suggests a link between sexuality, self-concept, and mental health.


AKT-targeted anti-inflammatory activity of the methanol extract of Chrysanthemum indicum var. albescens.
Wild chrysanthemum (Chrysanthemum indicum) is one of well-known medicinal plants traditionally used in Korea and China. As a variant of wild chrysanthemum, white wild chrysanthemum (Chrysanthemum indicum var. albescens) is also ethnopharmacologically applied to treat various symptoms such as inflammatory diseases. Although the anti-inflammatory activity of Chrysanthemum indicum has been reported, the anti-inflammatory activity and underlying molecular mechanism of white wild chrysanthemum are poorly understood. The effects of Chrysanthemum indicum var. albescens methanol extract (Civ-ME) on the production of inflammatory mediators, expression of pro-inflammatory genes, cell viability, and the activities of intracellular signaling molecules and transcription factors were investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Civ-ME suppressed the production of both nitric oxide (NO) and prostaglandin E2 (PGE2) without cytotoxicity in LPS-stimulated RAW264.7 cells. Civ-ME was found to reduce the mRNA levels of inflammatory genes such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α and reduced NF-κB-mediated transcriptional activation. Civ-ME inhibited the nuclear translocation of NF-κB (p65 and p50), and its upstream signaling composed of IκBα and IKKα/β. An NF-κB luciferase reporter gene assay and an in vitro kinase assay confirmed that AKT1 and AKT2 might be direct pharmacological targets of Civ-ME. In addition, luteolin was identified by HPLC analysis as the main active pharmacological components of Civ-ME. Civ-ME exerts an anti-inflammatory effect by targeting AKT1 and AKT2 in the NF-κB signaling pathway in macrophage-mediated inflammatory responses.


Neuroimmunological findings of Angiostrongylus cantonensis meningitis in Ecuadorian patients.
Meningitis caused by Angiostrongylus cantonensis has recently been reported in patients resulting from the first outbreaks in subtropical regions of Ecuador. Eight young adult patients from the two outbreaks were studied. IgA, IgM, IgG and albumin in cerebrospinal fluid and serum were quantified and plotted in cerebrospinal fluid/serum quotient diagrams (Reibergrams). The anamnesis on the patients included asking about any consumption of raw snails, symptoms and harm caused. Mean eosinophilia of 7.5% and 26% in serum and cerebrospinal fluid respectively was observed, as well as a moderate increase in total proteins. The most frequent pattern of intrathecal synthesis was observed in three classes of immunoglobulins. Intrathecal synthesis of IgM was observed in all cases two weeks after the first symptoms appeared. The intrathecal synthesis patterns of eosinophilic meningitis due to Angiostrongylus cantonensis, facilitated by cerebrospinal fluid analysis, were similar to those of previous cases from abroad.


Overweight Relation to Liver Fluke Infection among Rural Participants from 4 Districts of Nakhon Ratchasima Province, Thailand.
A cross-sectional survey was conducted among 730 participants from 4 rural districts of Nakhon Ratchasima province, Thailand, with a reported high incidence of liver fluke infection. This study was aimed to examine and evaluate the nutritional status in relation to Opisthorchis viverrini infection. Participants were purposive selected from Chum Phuang, Mueang Yang, Bua Yai, and Kaeng Sanam Nang districts. Stool samples were prepared by Kato Katz technique and then assessed by microscopy. Anthropometry was evaluated according to the body mass index from weight and height. Descriptive statistics and Spearman rank correlation coefficients were used to evaluate the association between the nutritional status and O. viverrini infection. Of 1.64% infected with O. viverrini the highest proportions were found in age groups ≥61 and 41-50 years old, Mueang Yang district. The majorities of participants had normal weight (32.2%), followed by class II obesity (28.1%), class I obesity (21.8%), underweight (10.3%), and class III obesity (8.63%). Nutritional status with class II obesity (rS=0.639, <0.01) and class I obesity (rS=0.582, <0.05), had moderately statistical significant correlations with O. viverrini infection. Meanwhile, normal weight (rS=0.437, <0.05) and class III obesity (rS=0.384, <0.05) demonstrated lower statistical significance. These findings raise the possibility that infection with O. viverrini may contribute to fat deposition and thereby have long-term consequences on human health. Further studies are needed to better understand whether O. viverrini contributes directly to fat deposition and possible mechanisms.


Inflammatory mechanisms in post-traumatic osteoarthritis: a role for CaMKK2.
Post-traumatic osteoarthritis (PTOA) is a multifactorial disease of the cartilage, synovium, and subchondral bone resulting from direct joint trauma and altered joint mechanics after traumatic injury. There are no current disease-modifying therapies for PTOA, and early surgical interventions focused on stabilizing the joint do not halt disease progression. Chronic pain and functional disability negatively affect the quality of life and take an economic toll on affected patients. While multiple mechanisms are at play in disease progression, joint inflammation is a key contributor. Impact-induced mitochondrial dysfunction and cell death or altered joint mechanics after trauma culminate in inflammatory cytokine release from synoviocytes and chondrocytes, cartilage catabolism, suppression of cartilage anabolism, synovitis, and subchondral bone disease, highlighting the complexity of the disease. Current understanding of the cellular and molecular mechanisms underlying the disease pathology has allowed for the investigation of a variety of therapeutic strategies that target unique apoptotic and/or inflammatory processes in the joint. This review provides a concise overview of the inflammatory and apoptotic mechanisms underlying PTOA pathogenesis and identifies potential therapeutic targets to mitigate disease progression. We highlight Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a serine/threonine protein kinase that was recently identified to play a role in murine and human osteoarthritis pathogenesis by coordinating chondrocyte inflammatory responses and apoptosis. Given its additional effects in regulating macrophage inflammatory signaling and bone remodeling, CaMKK2 emerges as a promising disease-modifying therapeutic target against PTOA.


[Clinical study of patients with nocturnal asthmatic attacks admitted to an emergency room].
Over the periods of a year, we studied the patients who were admitted to the emergency room at our hospital at night with asthmatic attacks. From July 1991 to June 1992, 10,932 patients were admitted to the internal department of our emergency room, 707 (6.5%) of them because of asthmatic attacks. These 707 consisted of 364 patients (51.5%) with mild attacks, 242 (34.2%) with moderate attacks and 101 (14.3%) with severe attacks according to Mitsui's score. Most patients admitted before 23:00 and after 5:00, but more patients with severe attacks were admitted around midnight. A large part of the patients with moderate or severe attacks had chronic hypoxemia, and more than half of the patients' serum theophylline concentration was under the therapeutic rate. More than half patients were treated within 5 minutes. But within those who were not, 6 patients with mild attacks on admission needed hospitalization later. For prevention of life threatening attack, we should regard it as an important problem to follow up the patients who don't come to the hospital in the daytime in spite of frequent visits to the emergency room at night.


Improving Refill Adherence in Medicare Patients With Tailored and Interactive Mobile Text Messaging: Pilot Study.
Nonadherence is a major concern in the management of chronic conditions such as hypertension, cardiovascular disease, and diabetes where patients may discontinue or interrupt their medication for a variety of reasons. Text message reminders have been used to improve adherence. However, few programs or studies have explored the benefits of text messaging with older populations and at scale. In this paper, we present a program design using tailored and interactive text messaging to improve refill rates of partially adherent or nonadherent Medicare members of a large integrated health plan. The aim of this 3-month program was to gain an understanding of whether tailored interactive text message dialogues could be used to improve medication refills in Medicare patients with one or more chronic diseases. We used the mPulse Mobile interactive text messaging solution with partially adherent and nonadherent Medicare patients (ie, over age 65 years or younger with disabilities) of Kaiser Permanente Southern California (KP), a large integrated health plan, and compared refill rates of the text messaging group (n=12,272) to a group of partially adherent or nonadherent Medicare patients at KP who did not receive text messages (nontext messaging group, n=76,068). Both groups were exposed to other forms of refill and adherence outreach including phone calls, secure emails, and robo-calls from December 2016 to February 2017. The text messaging group and nontext messaging group were compared using an independent samples t test to test difference in group average of refill rates. There was a significant difference in medication refill rates between the 2 groups, with a 14.07 percentage points higher refill rate in the text messaging group (P<.001). The results showed a strong benefit of using this text messaging solution to improve medication refill rates among Medicare patients. These findings also support using interactive text messaging as a cost-effective, convenient, and user-friendly solution for patient engagement. Program outcomes and insights can be used to enhance the design of future text-based solutions to improve health outcomes and promote adherence and long-term behavior change.


What constitutes urgent endoscopy? A social media snapshot of gastroenterologists' views during the COVID-19 pandemic.
Background and study aims There is a consensus among gastroenterology organizations that elective endoscopic procedures should be deferred during the COVID-19 pandemic. While the decision to perform urgent procedures and to defer entirely elective procedures is mostly evident, there is a wide "middle ground" of time-sensitive but not technically urgent or emergent endoscopic interventions. We aimed to survey gastroenterologists worldwide using Twitter to help elucidate these definitions using commonly encountered clinical scenarios during the COVID-19 pandemic. Methods A 16-question survey was designed by the authors to include common clinical scenarios that do not have clear guidelines regarding the timing or urgency of endoscopic evaluation. This survey was posted on Twitter. The survey remained open to polling for 48 hours. During this time, multiple gastroenterologists and fellows with prominent social media presence were tagged to disseminate the survey. Results The initial tweet had 38,795 impressions with a total of 2855 engagements. There was significant variation in responses from gastroenterologists regarding timing of endoscopy in these semi-urgent scenarios. There were only three of 16 scenarios for which more than 70 % of gastroenterologists agreed on procedure-timing . For example, significant variation was noted in regard to timing of upper endoscopy in patients with melena, with 44.5 % of respondents believing that everyone with melena should undergo endoscopic evaluation at this time. Similarly, about 35 % of respondents thought that endoscopic retrograde cholangiopancreatography should only be performed in patients with choledocholithiasis with abdominal pain or jaundice. Conclusion Our analysis shows that there is currently lack of consensus among gastroenterologists in regards to timing of semi-urgent or non-life-threatening procedures during the COVID-19 pandemic. These results support the need for the ongoing development of societal guidance for these "semi-urgent" scenarios to help gastroenterologists in making difficult triage decisions.


Community Insights in Phylogenetic HIV Research: The CIPHR Project Protocol.
Inferring HIV transmission networks from HIV sequences is gaining popularity in the field of HIV molecular epidemiology. However, HIV sequences are often analyzed at distance from those affected by HIV epidemics, namely without the involvement of communities most affected by HIV. These remote analyses often mean that knowledge is generated in absence of lived experiences and socio-economic realities that could inform the ethical application of network-derived information in 'real world' programmes. Procedures to engage communities are noticeably absent from the HIV molecular epidemiology literature. Here we present our team's protocol for engaging community activists living in Nairobi, Kenya in a knowledge exchange process - The CIPHR Project (Community Insights in Phylogenetic HIV Research). Drawing upon a community-based participatory approach, our team will (1) explore the possibilities and limitations of HIV molecular epidemiology for key population programmes, (2) pilot a community-based HIV molecular study, and (3) co-develop policy guidelines on conducting ethically safe HIV molecular epidemiology. Critical dialogue with activist communities will offer insight into the potential uses and abuses of using such information to sharpen HIV prevention programmes. The outcome of this process holds importance to the development of policy frameworks that will guide the next generation of the global response.


We will all age and one day be older adults ourselves: College students' reflections on facilitating compassionate presence (CP) sessions for older adults.
College students are likely to hold negative ageist views and attitudes toward older people. The compassionate presence (CP) intervention could be a promising approach to reduce ageist attitudes that younger adults have of older adults. College students were trained virtually in deep, active, and compassionate listening and were matched with older adults living in assisted-living facilities. The partners met virtually for an hour once per week. Students completed weekly reflections throughout the ten-week intervention. The weekly reflections revealed that students had preconceived notions about older adults before the CP training. After the CP training and throughout the intervention, we noted a positive shift in perception, knowledge, and attitudes toward older adults and aging. Students built meaningful social bonds with older adults, developed strong communication and interpersonal skills, and acquired research and core leadership skills needed for future careers and professional practice.


Clinical effects of 2 commercially available diets on canine atopic dermatitis.
Canine atopic dermatitis (CAD) is a common skin disease in dogs. Prior studies were able to determine beneficial effects of essential fatty acids (EFA) on the clinical signs of CAD. The aim of this study was set to evaluate the effects of a newly designed, EFA-enriched diet on the clinical signs of CAD compared to another EFA-enriched diet. In this prospective, randomized, double-blinded study, 31 privately owned dogs with atopic dermatitis received either the control diet (diet A, Hill's Prescription Diet™ d/d™ Salmon & Rice, n = 17) or the test diet (diet B, Veterinary HPM™ Dermatology Support D1, Virbac, n = 14) for 12 weeks. At the beginning of the study as well as after 4, 8 and 12 weeks, skin lesions and pruritus were evaluated via validated scores and the administered medication was documented. At the same time, the dogs' coat quality was evaluated via a distinct scoring system. In both groups, a total of 7 dogs each completed the entire study. After 12 weeks, there was a mild improvement in lesion scores, pruritus and coat quality with both diets. In this study, both diets improved the patients' skin lesions pruritus and coat quality.


JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer.
Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear. We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR and immunofluorescence staining to characterize novel CRC immune biomarkers. The effects of selective antagonists were tested by in vitro assays of long term viability and analysis of kinase active forms using anti-phospho antibodies. We identified the lymphocyte antigen 6 complex, locus G6D (LY6G6D) as significantly overexpressed (around 15-fold) in CRC when compared with its relatively low expression in other human solid tumours. LY6G6D up-regulation was predominant in MSS CRCs characterized by an enrichment of immune suppressive regulatory T-cells and a limited repertoire of PD-1/PD-L1 immune checkpoint receptors. Coexpression of LY6G6D and CD15 increases the risk of metastatic relapse in response to therapy. Both JAK-STAT5 and RAS-MEK-ERK cascades act in concert as key regulators of LY6G6D and Fucosyltransferase 4 (FUT4), which direct CD15-mediated immune-resistance. Momelotinib, an inhibitor of JAK1/JAK2, consistently abrogated the STAT5/LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting. Notably, colon cancer cells can evade JAK2/JAK1-targeted therapy by a reversible shift of the RAS-MEK-ERK pathway activity, which explains the treatment failure of JAK1/2 inhibitors in refractory CRC. Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human MSS CRC.


Impact of European Union label changes to avoid inadvertent use of medicinal products containing methotrexate for once-weekly administration: A survey amongst prescribers, pharmacists and patients on awareness, knowledge, and behaviour.
To determine the effectiveness of risk minimisation measures (RMM) to avoid inadvertent daily instead of weekly methotrexate (MTX) use, introduced by the European Medicines Agency (EMA) from 2019 onwards. Using a cross-sectional online survey in France, Greece, Germany, Poland, and Sweden in 2022, we assessed awareness, knowledge, and self-declared behaviour for respondents who prescribed, dispensed, or used once-weekly MTX in the last 3 months. Respondents' answers were considered as 'successful' with regards to RMM effectiveness (vs. unsuccessful) if they provided correct ('desirable') responses to 100% of questions regarding awareness and self-declared behaviour and correct responses to ≥80% of questions about knowledge. Per target population, an outcome was considered successful if achieved by ≥80% of respondents. Effectiveness of RMM was defined by ≥80% being successful on all outcomes. One-hundred-fifty-one prescribers, 150 pharmacists, and 150 patients completed the survey. Success rates were 56% (95% CI 48.0%-64.3%) for awareness, 42% (95% CI 34.4%-50.7%) for knowledge, and 31% (95% CI 23.8%-39.2%) for self-declared behaviour among prescribers, 18% (95% CI 12.8%-25.8%) for awareness, 7% (95% CI 3.7%-12.7%) for knowledge, and 50% (95% CI 41.7%-58.3%) for self-declared behaviour among pharmacists, and 29% (95% CI 21.6%-36.6%) for awareness, and 3% (95% CI 1.1%-7.6%) for knowledge among patients. Overall success was not attained by any target population. RMM were evaluated as not effective across outcomes of awareness, knowledge, and self-declared behaviour in prescribers, pharmacists, and patients. Findings suggested we need continued efforts for RMM across all target populations and across all outcomes.


Pilot Testing and Implementation of a mHealth tool for Non-communicable Diseases in a Humanitarian Setting.
Given the protracted nature of the crisis in Syria, national and international assistance agencies face immense challenges in providing for the needs of refugees and the host Lebanese due to the high burden of noncommunicable diseases (NCDs) among both populations. These are complex conditions to manage, and the resources for refugee care limited, having dramatic implications for Lebanon's health system. A longitudinal cohort study was implemented from January 2015 through August 2016 to evaluate the effectiveness of treatment guidelines and an mHealth application on quality of care and health outcomes for patients in primary health care facilities in Lebanon serving Syrian refugees and host communities. Overall, reporting in clinic medical records remained low, however, during the mHealth phase recording of BMI and blood pressure were significantly greater in the mHealth application as compared to clinic medical records. Patient exit interviews reported a much more frequent measurement of weight, height, blood pressure, and blood glucose, suggesting these may be assessed more often than they are recorded. Satisfaction with the clinic visit improved significantly during implementation of the mHealth application as compared to both baseline and guidelines implementation in all measures. Despite positive changes, provider uptake of the application was low; patients indicated that the mHealth application was used in a minority (21.7%) of consultations. Provider perspectives on how the application changed patient interactions were mixed. Similar to previous evidence, this study further demonstrates the need to incorporate new interventions with existing practices and reporting requirements to minimize duplication of efforts and, consequently, strengthen provider usage. Additional research is needed to identify organizational and provider-side factors associated with uptake of similar applications, particularly in complex settings, to optimize the benefit of such tools.


Evaluating diagnostic accuracies of Panbio™ test and RT-PCR for the detection of SARS-CoV-2 in Addis Ababa, Ethiopia using Bayesian Latent-Class Models (BLCM).
Rapid diagnostics are vital for curving the transmission and control of the COVID-19 pandemic. Although many commercially available antigen-based rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 are recommended by the WHO, their diagnostic performance has not yet been assessed in Ethiopia. So far, the vast majority of studies assessing diagnostic accuracies of rapid antigen tests considered RT-PCR as a reference standard, which inevitably leads to bias when RT-PCR is not 100% sensitive and specific. Thus, this study aimed to evaluate the diagnostic performance of Panbio™ jointly with the RT-PCR for the detection of SARS-CoV-2. A prospective cross-sectional study was done from July to September 2021 in Addis Ababa, Ethiopia, during the third wave of the pandemic involving two health centers and two hospitals. Diagnostic sensitivity and specificity of Panbio™ and RT-PCR were obtained using Bayesian Latent-Class Models (BLCM). 438 COVID-19 presumptive clients were enrolled, 239 (54.6%) were females, of whom 196 (44.7%) had a positive RT-PCR and 158 (36.1%) were Panbio™ positive. The Panbio™ and RT-PCR had a sensitivity (95% CrI) of 99.6 (98.4-100) %, 89.3 (83.2-97.6) % and specificity (95% CrI) of 93.4 (82.3-100) %, and 99.1 (97.5-100) %, respectively. Most of the study participants, 318 (72.6%) exhibited COVID-19 symptoms; the most reported was cough 191 (43.6%). As expected the RT-PCR performed very well with a near-perfect specificity and a high, but not perfect sensitivity. The diagnostic performance of Panbio™ is coherent with the WHO established criteria of having a sensitivity ≥80% for Ag-RDTs. Both tests displayed high diagnostic accuracies in patients with and without symptoms. Hence, we recommend the use of the Panbio™ for both symptomatic and asymptomatic individuals in clinical settings for screening purposes.


Effect of blinding with a new pragmatic placebo needle: a randomized controlled crossover study.
Placebo control is a useful method for determining the efficacy of a therapy. In acupuncture researches, the preferred method for placebo control is acupuncture using a placebo needle that has a blunt tip and achieves no skin penetration. We performed a crossover study to validate the blinding effect of a new type of placebo needle. Sixty volunteers were randomized to receive acupuncture using 2 types of needles with different sequences: sequence AB, involving first the pragmatic placebo needle and then the real needle, and sequence BA, in a reverse order. Placebo acupuncture was performed by administering the placebo needle through an adhesive pad without skin penetration on the acupoints LI4, RN12, BL25, and BL36. Real acupuncture was performed by needling through the pad and penetrating the skin to 15 mm using a real needle on the same acupoints. The acupuncture was administered every other day with 3 sessions for 1 type of needle. The primary outcome was the perception of needle penetration. Besides degree of acupuncture pain, type, and degree of needle sensation, needle acceptability and factors influencing the subject blinding effect were assessed. Needle penetration was felt by 100%, 90% (54/60), 88.3% (53/60), and 95% (57/60) of volunteers receiving placebo acupuncture and 98.3% (59/60), 96.7% (58/60), 95% (57/60), and 95% (57/60) of volunteers receiving real acupuncture on LI4, RN12, BL25, and BL36, respectively. Differences of the volunteers' perception of needle penetration between the placebo needle and real needle were not significant for the 4 acupoints (all P > 0.05). Volunteers experienced fewer distension sensations (P = 0.01), a lower degree of needle sensation (P = 0.007), and less pain (P = 0.006) during placebo acupuncture than during real acupuncture. The placebo needle was more easily accepted than the real needle (OR = 1.63, 95% CI, 1.01-2.64). The influences of age, sex, educational level, acupuncture experience, needle sensation, acupuncture pain, and needle acceptability on volunteers' perception of needle penetration were not significant. The pragmatic placebo needle is a valid control for acupuncture research. It produces a good subject blinding effect with a similar appearance to conventional acupuncture needles and no skin penetration when applied.


Intrinsic innervation in the tracheal smooth muscle of the large flying fox (Pteropus vampyrus): an immunohistochemical study.
Structure and innervation of the trachea of the large flying fox (Pteropus vampyrus) were examined by mean hematoxylin-eosin staining and immunohistochemical methods. The tracheal rings were predominantly comprised of bone with a small amount of hyaline cartilage. Bone contained bone marrow and hyaline cartilage attached at the ends of the tracheal rings. The tracheal rings in the anterior third of the trachea were connected at each end with connective tissue to almost form a ring. A narrow membranous wall comprising a single layer of smooth muscle was present in the middle third, while inner and outer layers of smooth muscle were present in the posterior third. Protein gene product 9.5 (PGP 9.5)-, nitric oxide synthase (NOS)-, galanin- and vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers were present in the epithelium, lamina propria, smooth muscle layer and tunica adventitia. In the tunica adventitia, many PGP 9.5- and NOS-immunoreactive neurons were found singly or in small ganglia, while some VIP- and galanin-immunoreactive neurons were observed. A few PGP 9.5- and NOS-immunoreactive neurons were found in the submucosal layer. These results suggest that the trachea of the large flying fox has a rigid structure of tracheal rings and that the posterior two-thirds of the trachea probably contract via the actions of smooth muscles innervated with peptidergic or nitrenergic neurons that are located in tracheal ganglia, whereas the anterior third is non-mobile.


Comparative Evaluation of Water Sorption, Solubility, and Microhardness of Zirconia-reinforced Glass Ionomer, Resin-modified Glass Ionomer, and Type IX Glass Ionomer Restorative Materials: An In Vitro Study.
The challenge that practicing dentists face every day is to decide which dental material is best suited for each dental treatment. New glass-ionomer cement (GIC) formulations have been introduced in order to overcome the drawbacks of conventional ones thereby catering to the needs of the pediatric population. The study aimed to evaluate and compare water sorption, solubility, and microhardness of zirconia-reinforced glass ionomer, resin-modified glass ionomer, type IX glass ionomer cements. 90 specimens were prepared in total of which 45 cylindrical specimens with dimensions of (6 × 4) mm and 45 disks with (10 × 2) mm were prepared from Zirconomer, RMGIC, and Type IX GIC restorative materials, each material having 30 specimens (15 disks, 15 cylinders). After taking the initial weight (W1), the 45 cylinders (15 of each material) were immersed in artificial saliva at 37°C for 28 days after which the weights W2 and W3 were weighed. The other 45 disks (15 of each material) were subjected to microhardness test under microhardness tester. Results were subjected to ANOVA and Tuckey's post hoc test. Zirconomer showed the maximum resistance to water sorption and solubility followed by RMGIC and type IX GIC with a significant p value of < 0.001 difference. For microhardness, Zirconomer showed the highest value with a significant p value of < 0.001 difference. But, there was no significant difference between RMGIC and Type IX GIC depicting almost equal strength. Water sorption, solubility, and microhardness of Zirconomer were significantly high in comparison to the other groups and it can be used as a posterior restorative material for stress-bearing areas. As pediatric dentistry demands restorations to be completed frequently in less than ideal conditions, Zirconomer has shown to be better than RMGIC and conventional GIC probably because of the improvisation in the GIC properties. Bethapudy DR, Bhat C, Lakade L, et al. Comparative Evaluation of Water Sorption, Solubility, and Microhardness of Zirconia-reinforced Glass Ionomer, Resin-modified Glass Ionomer, and Type IX Glass Ionomer Restorative Materials: An In Vitro Study. Int J Clin Pediatr Dent 2022;15(2):175-181.


Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke.
Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90. The patients' mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9-11, P=0.008) and day 90 (median 11, interquartile range 10-13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%). Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke.


Trends of Human Plague, Madagascar, 1998-2016.
Madagascar is more seriously affected by plague, a zoonosis caused by Yersinia pestis, than any other country. The Plague National Control Program was established in 1993 and includes human surveillance. During 1998-2016, a total of 13,234 suspected cases were recorded, mainly from the central highlands; 27% were confirmed cases, and 17% were presumptive cases. Patients with bubonic plague (median age 13 years) represented 93% of confirmed and presumptive cases, and patients with pneumonic plague (median age 29 years) represented 7%. Deaths were associated with delay of consultation, pneumonic form, contact with other cases, occurrence after 2009, and not reporting dead rats. A seasonal pattern was observed with recrudescence during September-March. Annual cases peaked in 2004 and decreased to the lowest incidence in 2016. This overall reduction occurred primarily for suspected cases and might be caused by improved adherence to case criteria during widespread implementation of the F1 rapid diagnostic test in 2002.


Determining feeding tube location by gastric and intestinal pH values.
The purpose of this study was to evaluate a series of pH values of aspirates from feeding tubes to differentiate between gastric and intestinal tube placement. One hundred ventilator-supported subjects, with an order for nasoduodenal feeding tube placement were randomly selected. The feeding tube was placed into the stomach, verified by auscultation, and 2 pH measurements were obtained. After the pH measurements were taken, tube location was then verified by fluoroscopy. When the tube was advanced into the small intestine, location was verified by fluoroscopy, and 2 additional pH measurements were obtained. From the selected subjects, both a gastric and intestinal aspirate were obtained from 82 subjects. For the 82 subjects, the mean gastric and intestinal pH values were 4.8 +/- 2.3 and 7.1 +/- 1.0, respectively. For patients receiving acid-suppressing agents, these values were 5.0 +/- 2.3 and 7.2 +/- 1.0, respectively. For subjects not receiving acid-suppressing agents, these pH values were 4.0 +/- 2.5 and 6.7 +/- 1.1, respectively. For all patients, using a pH value of 6.5 as a predictor of feeding tube location, the sensitivity and specificity were 0.66 and 0.90. In addition, when an increase in pH > or = 1.0 was used as a predictor of location change for all patients, the sensitivity was 0.58. The pH value was a reliable predictor of nasoduodenal tube placement. However, radiographic confirmation of location could not be excluded because of the low sensitivity using pH measurements alone. An increase of > or = 1.0 in gastric vs intestinal pH specimens could be useful to determine use of radiography confirmation of tube placement.


Enzyme screening with synthetic multifunctional pores: focus on biopolymers.
This report demonstrates that a single set of identical synthetic multifunctional pores can detect the activity of many different enzymes. Enzymes catalyzing either synthesis or degradation of DNA (exonuclease III or polymerase I), RNA (RNase A), polysaccharides (heparinase I, hyaluronidase, and galactosyltransferase), and proteins (papain, ficin, elastase, subtilisin, and pronase) are selected to exemplify this key characteristic of synthetic multifunctional pore sensors. Because anionic, cationic, and neutral substrates can gain access to the interior of complementarily functionalized pores, such pores can be the basis for very user-friendly screening of a broad range of enzymes.


[Cortical atrophy in MRI, mental status and neuroleptic treatment effect in schizophrenia].
MR imaging of the head was performed in forty schizophrenics (DSM-IV). Mental status was evaluated before and during 8-weeks of neuroleptic treatment. Cortical atrophy in frontal and temporal regions was found in 40% of subjects. They were older, had longer history of schizophrenia, were less active professionally and were more frequently hospitalized. Patients with and without cortical atrophy in MRI did not differ in the severity of schizophrenic psychopathology at baseline. During neuroleptic treatment negative schizophrenia symptoms were significantly better diminished in patients without cortical atrophy than in subjects with cortical atrophy in MRI; this regarded specially the severity of emotional blunting. Clinical improvement after 8-weeks of neuroleptic administration was less favorable in patients with cortical atrophy.


Dental education profile in COVID-19 pandemic: A scoping review.
This scoping review aimed to determine the frequency of different teaching methodologies, tools and platforms applied in dental education during the COVID-19 pandemic. The search strategy was performed in six databases and grey literature. A total of 28 questionnaire-based studies were included, without language or time restriction, from 20 different countries. Six thousand five hundred sixty-five participants were assessed: 84% undergraduates, 9% of faculty members, 5% of postgraduate students/residents/trainees and 2% of dental schools/residency programs. The pooled eligible data for teaching methodologies were 62% of a combination of different methods (95% CI, 35.5% to 82.3%), 23% a combination of synchronous and asynchronous formats (95% CI, 8.2% to 50.2%) and 15% for only synchronous lectures (95% CI, 4.3% to 42.2%). The reported tools were laptops (40%), smartphones (40%), tablets (40%), desktops (20%), Blackboard (20%), Respondus Lockdown Browser (20%), eProctor (20%) and PowerPoint (20%). The most used platforms were Zoom (70.6%), Microsoft Teams (23.5%) and Cisco Webex (23.5%). A better time management (17.9%; 95% CI, 7.9% to 35.6%) and the possibility of revision with additional notes (14.3%; 95% CI, 5.7% to 31.5%) was the greatest advantages related to dental e-learning, while the increased levels of anxiety/stress/burnout/exhaustion (35.7%; 95% CI, 21% to 54.2%) and internet connection problems (35.7%; 95% CI, 21% to 54.2%) was the most cited disadvantages. This scoping review showed promising blended teaching methodologies, tools and platforms in the dental education profile. The evidence suggests that e-learning technologies can widely contribute to dental education during the COVID-19 pandemic. Therefore, this study makes a major contribution to research by assessing the impact of COVID restrictions on dental education and further studies are needed to identify how restrictions in dental practice will affect future professionals.


Nonrandom occurrence of lymphoid cancer types in 140 families.
We studied 140 families with two or more lymphoid cancers, including non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM), for deviation from the population age of onset and lymphoid cancer co-occurrence patterns. Median familial NHL, HL, CLL and MM ages of onset are substantially earlier than comparable population data. NHL, HL and CLL (but not MM) also show earlier age of onset in later generations, known as anticipation. The co-occurrence of lymphoid cancers is significantly different from that expected based on population frequencies (p < .0001), and the pattern differs more in families with more affected members (p < .0001), suggesting specific lymphoid cancer combinations have a shared genetic basis. These families provide evidence for inherited factors that increase the risk of multiple lymphoid cancers. This study was approved by the BC Cancer Agency - University of British Columbia Clinical Research Ethics Board.


Inductively Coupled Plasma Collision Cell Quadrupole Mass Spectrometric Determination of Extractible Arsenic, Cadmium, Chromium, Lead, Mercury, and Other Elements in Food Using Microwave-Assisted Digestion: Results from an FDA Interlaboratory Study.
Background: An interlaboratory study was conducted to test U.S. Food and Drug Administration (FDA) Elemental Analysis Manual (EAM) Method 4.7, "Inductively Coupled Plasma-Mass Spectrometric Determination of Arsenic, Cadmium, Chromium, Lead, Mercury, and Other Elements in Food Using Microwave Assisted Digestion." Objective: The goal of the study was to demonstrate the performance of FDA EAM Method 4.7. Methods: Fourteen laboratories participated in the collaborative study, including nine Food Emergency Response Network state laboratories and five federal FDA laboratories. Laboratories tested 8 labeled standard reference materials and 12 blinded foods: mayonnaise, dark chocolate, sunflower seeds, hamburger with cheese, brown rice flour (blinded reference material included as a test food), infant formula, canned smoked oysters, sardines in tomato paste, swordfish, mineral water, cinnamon, and a multivitamin. The blinded test foods represented every sector of the AOAC food triangle. Participants measured the mass fraction of each element in each sample in triplicate. Results: Horwitz Ratio (HorRat) values were better than 1.5 for all As, Cd, Cu, Hg, Mo, Ni, Pb, and Se measurements when at least eight laboratories reported results greater than LOQ. The HorRat values were better than 1.5 for all Mn and Zn measurements except for the multivitamin and for all Cr measurements except for sunflower seeds, in which the nonhomogeneity was identified. The average HorRat value of the blinded test foods was 0.66 for results greater than LOQ (n = 4206). Conclusions: The study showed that the method performed satisfactorily as a standard method for extractible elemental analysis of food. Highlights: The method met or exceeded the performance expected.


Double-stranded RNA binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins.
In response to viral infection, cells activate a variety of antiviral responses, including several that are triggered by double-stranded (ds) RNA. Among these are the protein kinase R and oligoadenylate synthetase/RNase L pathways, both of which result in the shutoff of protein synthesis. Many viruses, including human cytomegalovirus, encode dsRNA-binding proteins that prevent the activation of these pathways and thereby enable continued protein synthesis and viral replication. We have extended these analyses to another member of the beta subfamily of herpesviruses, murine cytomegalovirus (MCMV), and now report that products of the m142 and m143 genes together bind dsRNA. Coimmunoprecipitation experiments demonstrate that these two proteins interact in infected cells, consistent with their previously reported colocalization. Jointly, but not individually, the proteins rescue replication of a vaccinia virus mutant with a deletion of the dsRNA-binding protein gene E3L (VVDeltaE3L). Like the human cytomegalovirus dsRNA-binding protein genes TRS1 and IRS1, m142 and m143 are members of the US22 gene family. We also found that two other members of the MCMV US22 family, M23 and M24, encode dsRNA-binding proteins, but they do not rescue VVDeltaE3L replication. These results reveal that MCMV, like many other viruses, encodes dsRNA-binding proteins, at least two of which can inhibit dsRNA-activated antiviral pathways. However, unlike other well-studied examples, the MCMV proteins appear to act in a heterodimeric complex.


Left ventricular contractile function is preserved during prolonged exercise in middle-aged men.
We examined left ventricular (LV) performance before, during, and following prolonged exercise (EX) in 12 healthy middle-aged men [means +/- SE: age = 43.5 +/- 1.9 yr; maximal O(2) uptake (Vo(2max)) = 51.7 +/- 1.5 ml.kg(-1).min(-1)]. Subjects cycled for 120 min at 65% Vo(2max) (75% of maximal heart rate). Two-dimensional echocardiography (ECHO) to determine tissue-Doppler longitudinal myocardial strain and strain rate, LV ejection fraction (EF), end-diastolic (EDV), end-systolic (ESV), and stroke volume (SV) at baseline and after 5, 30, and 120 min of EX and following 30 min of recovery. In addition, hematocrit and plasma norepinephrine (NE) were measured. From baseline to 5 min of EX, there were significant increases in LV longitudinal strain (-23.20 +/- 0.87 to -27.63 +/- 1.07%; P < 0.01), strain rate (-1.50 +/- 0.15 to -2.08 +/- 0.14 s(-1); P < 0.01), and EF (56.3 +/- 2.2 to 77.1 +/- 1.0%; P < 0.05) with continued increases by both at 30 min of exercise vs. SV, EDV, and ESV, which remained constant. After 120 min of EX, HR and NE increased further with reductions in SV, cardiac output, and systolic blood pressure without changes in strain or strain rate. EDV decreased after 120 min of EX (-9.2- vs. 30-min value; P = 0.05) along with a hemoconcentration (baseline = 41.3 +/- 1.0 vs. EX = 45.1 +/- 1.2%; P < 0001) and significant reduction in body mass despite a mean fluid consumption of 1.8 +/- 0.2 liters throughout EX. After 30 min of recovery, LV longitudinal strain was depressed relative to baseline (-23.20 +/- 0.87 to -19.57 +/- 1.21%; P < 0.01). The reduction in LV SV during prolonged EX occurred without changes in the LV contractile state and is likely secondary to reduced LV preload. A reduction in LV contractility despite a reduced afterload following exercise may be due to factors unique to the recovery period and do not appear to contribute to a reduction in SV during prolonged exercise.


Skin Diseases in a Pediatric Hospital of Nepal.
The skin diseases of pediatric population are varied which change according to age and season. There is a rarity of studies on pediatric skin conditions from Nepal. This observational study from the only tertiary care referral pediatric center of the country highlighted the burden of pediatric skin diseases in Nepalese population. All new cases of pediatric patients less than 14 years of age consulting the pediatric dermatological OPD of Kanti Children's Hospital from January 2017 to December 2017 were included in this study. Demographic details of all the patients such as age and sex were recorded. The diagnosis was made clinically in most instances and appropriate laboratory and histopathological examination were performed wherever necessary. A total of 7683 pediatric patients were included in the study. Among these, there were 4574 (59.53%) males and 3109 (40.47%) females. The most common skin condition was infections among 2463 (32.12%) followed by eczematous conditions in 1711(22.27%) and hypersensitivity reactions in 1510 (19.65%). Infections were more common during the summer months. Overall, both infectious and noninfectious skin diseases were significantly more common during the warmer (summer and spring) months as compared to colder (autumn and winter) months (p < 0.001). This study shows that the pediatric dermatoses are common in Nepalese population.


[Not Available].
The present article gives an overview of the current state of laryngeal surgery of benign lesions without claiming completeness and with a focus on the ENT board exam. Laryngeal procedures are highly endoscopic and microscopic based. New instruments and high-resolution endoscopic imaging techniques may substitute the typical Kleinsasser approach in the near future. Additionally, new flexible endoscopes may initiate a new era of so-called "office-based surgery". Furthermore, a consistent education of the public about performing vocal hygiene is necessary to prevent the rise of laryngeal diseases.


[Primary diffuse large B-cell lymphoma of central nervous system belongs to activated B-cell-like subgroup: a study of 47 cases].
To investigate the histogenetic origin of primary central nervous system diffuse large B-cell lymphoma (DLBCL) with respect to the stage of B-cell differentiation, and identification of the relevant prognostic markers. Immunohistochemical staining (EnVision method) for CD10, bcl-6, MUM-1, CD138 and FOXP1 antigens was performed on 47 paraffin-embedded sections. CD10, bcl-6, MUM-1 and FOXP1 expression in the tumor cells were 6.4%, 53.2%, 91.5% and 93.6% respectively. There was no expression of CD138 in all the cases. Among the 47 patients, 43 cases (91.5%) showed an activated B-cell-like (ABC) phenotype: 21 (44.7%) were bcl-6+ and MUM-1+, suggesting an "activated germinal center (GC) B-cell-like" in origin; 22 (46.8%) were exclusively MUM-1+, suggesting an "activated non-GCB" in origin. No significant correlation of the classification and FOXP1 expression found on the outcome (P=0.279 and P=0.154). Most primary central nervous system DLBCL are shown belonging to the ABC subgroup, suggesting that primary central nervous system DLBCL is quite similar to a DLBCL subset, which is derived from late GC to early post-GC B cell. The classification and FOXP1 expression do not show prognostic value in primary central nervous system DLBCL.


Removal of adherent cortical vitreous plaques without removing the internal limiting membrane in the repair of macular detachments in highly myopic eyes.
To report anatomic and visual improvement after vitrectomy with removal of adherent plaques of vitreous and gas tamponade in highly myopic eyes with detachments over posterior staphylomata. Eyes with retinal detachment over staphylomata were treated with vitrectomy and vitreous cortex removal. Adherent plaques of vitreous were invariably found on the detached retina and were easier to identify with the aid of intraocular triamcinolone. Removal of the vitreous plaques and placement of long-acting gas affected surgical repair. Outcome measures included best-corrected visual acuity and retina reattachment confirmed by biomicroscopic appearance and optical coherence tomography findings. Six eyes of five consecutive patients were treated. The mean preoperative best-corrected visual acuity was 20/100, and the mean time of documented detachment was 21 months. The internal limiting membrane was not removed in any patient. After surgery, all patients' retinas remained attached during the mean follow-up period of 19.1 months. At the end of the follow-up period, the mean best-corrected visual acuity was 20/60, an improvement that was statistically significant (P = 0.027). Retinal detachment over staphylomata in highly myopic eyes appears to be tractional from unresolved forces caused by adherent plaques of vitreous. Removal of the vitreous, without removing the internal limiting membrane, can reattach the retina and lead to anatomic and visual acuity improvements.


Compatibility of a combination of tiamulin and chlortetracycline with salinomycin in feed during a pulsed medication program coadministration in broilers.
In an earlier study, the continuous medication of broiler feed with a combination of tiamulin (TIA; 20 mg/kg), chlortetracycline (CTC; 60 mg/kg), and the ionophore anticoccidial salinomycin (SAL; 60 mg/kg) caused an initial increase in BW and feed efficiency (FE; g of weight gain/kg of feed intake). However, as doses increased to combinations of 30 mg/kg of TIA and 90 mg/kg of CTC or 50 mg/kg of TIA and 150 mg/kg of CTC, there was a dose-related reduction in growth rate and FE. This was thought to be due to the interaction between TIA and SAL. In this study, using a protocol similar to the previous trial, broiler chicks were administered SAL at 60 mg/kg via the feed and the same inclusion rates of TIA + CTC. However, instead of feeding the birds continuously, considering the cost of TIA and possibly to compensate for the depressed growth attributable to the interaction with SAL, they were pulse-dosed for 1 to 10 d and again at 21 to 27 d, and the whole trial lasted 35 d to see if the intermittent pulses might reduce production losses. A total of 200 straight-run 1-d-old broiler chicks (Hubbard classic) were randomly distributed into 4 groups, with each group consisting of 5 cages containing 10 birds. The 20 cages were allocated to the 4 treatment groups on a random basis. The control diet, containing only SAL at 60 mg/kg, was fed to all birds throughout the 35-d trial, including the period during the gaps between dosing (i.e., d 11 to 20 and d 28 to 35). Feed and water were available for the whole trial period. Several serum enzymes (creatine kinase, lactate dehydrogenase, and aspartate aminotransferase) were determined from blood samples taken on d 35. Blood samples were also collected at 1, 19, and 35 d of age and were examined for antibody titers to Mycoplasma gallisepticum and Mycoplasma synoviae. Necropsy and histopathology of the birds (n = >or=4) were conducted during weekly intervals. There was no significant difference in weight gain, feed intake, and FE when the groups treated with TIA + CTC were compared with the control group (P > 0.05). There was no relationship between mortality and inclusion rates of the medication. No clinical signs of an interaction were exhibited during the trial, which was supported by necropsy and serum enzyme results. Maternally derived antibodies against M. gallisepticum were identified at the start of the trial but disappeared within 19 d, and infection with M. gallisepticum or M. synoviae was found neither serologically nor clinically during the trial. The results demonstrated that intermittent pulse administration of TIA at 50 mg/kg + CTC at 150 mg/kg from d 1 to 10 and d 21 to 27, along with continuous feeding of SAL (60 mg/kg), would be possible without altering performance and while maintaining the health status of the broilers. However, further research is required on the presence of artificial infections with Mycoplasma pathogens to determine the efficacy of the combination of TIA +CTC.