Acute effects of fine particulate matter constituents on mortality: A systematic review and meta-regression analysis.
The link between PM2.5 exposure and adverse health outcomes is well documented from studies across the world. However, the reported effect estimates vary across studies, locations and constituents. We aimed to conduct a meta-analysis on associations between short-term exposure to PM2.5 constituents and mortality using city-specific estimates, and explore factors that may explain some of the observed heterogeneity. We systematically reviewed epidemiological studies on particle constituents and mortality using PubMed and Web of Science databases up to July 2015.We included studies that examined the association between short-term exposure to PM2.5 constituents and all-cause, cardiovascular, and respiratory mortality, in the general adult population. Each study was summarized based on pre-specified study key parameters (e.g., location, time period, population, diagnostic classification standard), and we evaluated the risk of bias using the Office of Health Assessment and Translation (OHAT) Method for each included study. We extracted city-specific mortality risk estimates for each constituent and cause of mortality. For multi-city studies, we requested the city-specific risk estimates from the authors unless reported in the article. We performed random effects meta-analyses using city-specific estimates, and examined whether the effects vary across regions and city characteristics (PM2.5 concentration levels, air temperature, elevation, vegetation, size of elderly population, population density, and baseline mortality). We found a 0.89% (95% CI: 0.68, 1.10%) increase in all-cause, a 0.80% (95% CI: 0.41, 1.20%) increase in cardiovascular, and a 1.10% (95% CI: 0.59, 1.62%) increase in respiratory mortality per 10μg/m3 increase in PM2.5. Accounting for the downward bias induced by studies of single days, the all-cause mortality estimate increased to 1.01% (95% CI: 0.81, 1.20%). We found significant associations between mortality and several PM2.5 constituents. The most consistent and stronger associations were observed for elemental carbon (EC) and potassium (K). For most of the constituents, we observed high variability of effect estimates across cities. Our meta-analysis suggests that (a) combustion elements such as EC and K have a stronger association with mortality, (b) single lag studies underestimate effects, and (c) estimates of PM2.5 and constituents differ across regions. Accounting for PM mass in constituent's health models may lead to more stable and comparable effect estimates across different studies. PROSPERO: CRD42017055765.


Characterization of exogenous αSN response genes and their relation to Parkinson's disease using network analyses.
Despite extensive research, the molecular mechanisms underlying the toxicity of αSN in Parkinson's disease (PD) pathology are still poorly understood. To address this, we used a microarray dataset to identify genes that are induced and differentially expressed after exposure to toxic αSN aggregates, which we call exogenous αSN response (EASR) genes. Using systems biology approaches, we then determined, at multiple levels of analysis, how these EASR genes could be related to PD pathology. A key result was the identification of functional connections between EASR genes and previously identified PD-related genes by employing the proteins' interactions networks and 9 brain region-specific co-expression networks. In each brain region, co-expression modules of EASR genes were enriched for gene sets whose expression are altered by SARS-CoV-2 infection, leading to the hypothesis that EASR co-expression genes may explain the observed links between COVID-19 and PD. An examination of the expression pattern of EASR genes in different non-neurological healthy brain regions revealed that regions with lower mean expression of the upregulated EASR genes, such as substantia nigra, are more vulnerable to αSN aggregates and lose their neurological functions during PD progression. Gene Set Enrichment Analysis of healthy and PD samples from substantia nigra revealed that a specific co-expression network, "TNF-α signaling via NF-κB", is an upregulated pathway associated with the PD phenotype. Inhibitors of the "TNF-α signaling via NF-κB" pathway may, therefore, decrease the activity level of this pathway and thereby provide therapeutic benefits for PD patients. We virtually screened FDA-approved drugs against these upregulated genes (NR4A1, DUSP1, and FOS) using docking-based drug discovery and identified several promising drugs. Altogether, our study provides a better understanding of αSN toxicity mechanisms in PD and identifies potential therapeutic targets and small molecules for treatment of PD.


Prospective study on dosimetric comparison of helical tomotherapy and 3DCRT for craniospinal irradiation - A single institution experience.
This prospective study aims to assess feasibility of helical tomotherapy (HT) for craniospinal irradiation (CSI) and perform dosimetric comparison of treatment plans for both HT and 3D conformal radiotherapy (3DCRT). CSI is a challenging procedure. Large PTV size requires field matching due to technical limitations of standard linear accelerators, which cannot irradiate such volumes as a single field. HT could help to avoid these limitations as irradiation of long fields is possible without field matching. Three adults were enrolled from 2009 to 2010. All patients received radiochemotherapy. Treatment plans in prone position for 3DCRT and in supine position for HT were generated. The superior plan was used for patients' irradiation. Plans were compared with the application of DVH, Dx parameters - where x represents a percentage of the structure volume receiving a normalized dose and homogeneity index (HI). All patients received HT irradiation. The treatment was well tolerated. The HT plans resulted in a better dose coverage and uniformity in the PTV: HI were 5.4, 7.8, 6.8 for HT vs. 10.3, 6.6, 10.4 for 3DCRT. For most organs at risk (OARs), the D(V80) was higher for HT than for 3DCRT, whereas D(V5) was lower for HT. HT is feasible for CSI, and in comparison with 3DCRT it improves PTV coverage. HT reduces high dose volumes of OARs, but larger volumes of normal tissue receive low radiation dose. HT requires further study to establish correlations between dosimetrical findings and clinical outcomes, especially with regard to late sequelae of treatment.


Anti-rheumatic effect of quercetin and recent developments in nano formulation.
Rheumatoid arthritis (RA) is a common worldwide chronic autoimmune disease, characterised by synovial hyperplasia, inflammatory cell infiltration, pannus formation and destruction of articular cartilage and bone matrix. It is one of the most common forms of osteoarthritis bestowing high rates of both disability and death. Increasing attention has been paid to the use of natural medicines and natural products in the treatment of RA and patients' acceptance has increased year by year because of their high efficacy and safety. Flavonoids are a group of important secondary metabolites occurring in many plants which have rich biological activities such as anti-rheumatic, vasodilator, and anti-tumor effects. Many successful medical treatments of RA appear to be attributable to the application of flavonoids. Quercetin, a representative active member of the flavonoid family, is found abundantly in many plants, e.g. apples, berries, cabbages, onions, and ginkgo. In recent years, progress has been made in the research of its anti-rheumatoid effects which indicate that it is potentially a noteworthy prodrug for the treatment of RA. However, the poor solubility of quercetin affects its bioavailability and clinical efficacy. This review aims to provide an up to date summary of the biological effects and mechanism of action of quercetin for the treatment of RA, and the research progress made towards nano formulations of quercetin to improve its solubility and efficacy.


Effect of Transcutaneous Electric Nerve Stimulation on Pain after Total Knee Arthroplasty: A Blind Randomized Controlled Trial.
Transcutaneous electric nerve stimulation (TENS) has proven to be effective for postsurgical pain relief. However, there is a lack of well-constructed clinical trials investigating the effect of TENS after total knee arthroplasty (TKA). In addition, previous investigations reported that low- and high-frequency TENSs produced analgesic tolerance after 4 or 5 days of treatment. The aim of this study is to explore the effect of burst TENS on pain during hospitalization after TKA and to investigate whether burst TENS produces analgesic tolerance after 4 or 5 days of treatment. This stratified, triple blind, randomized controlled trial was approved by the University Hospital Brussels. Sixty-eight subjects were screened for eligibility before surgery; 54 were found eligible and 53 were included in the analyses. Patients were allocated to either a burst TENS or sham burst TENS group. TENS was applied daily during continuous passive mobilization. Knee pain intensity, knee range of motion, and analgesic consumption were assessed daily. Patients received burst TENS (N = 25) or sham burst TENS (N = 28). No significant differences in knee pain intensity were found between the groups (p > 0.05). Within the TENS and the sham TENS groups, the difference in knee pain before and after treatment did not evolve over time (p > 0.05). This study found no effects of burst TENS compared with sham burst TENS on pain during hospitalization after TKA.


What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy.
In the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia, and often the presence of some Rett-syndrome-like features. The association of CDKL5 with neurodevelopmental disorders and its high expression levels in the maturing brain underscore the importance of this kinase for proper brain development. However, our present knowledge of CDKL5 functions is still rather limited. The picture that emerges from the molecular and cellular studies suggests that CDKL5 functions are important for regulating both neuronal morphology through cytoplasmic signaling pathways and activity-dependent gene expression in the nuclear compartment. This paper surveys the current state of CDKL5 research with emphasis on the clinical symptoms associated with mutations in CDKL5, the different mechanisms regulating its functions, and the connected molecular pathways. Finally, based on the available data we speculate that CDKL5 might play a role in neuronal plasticity and we adduce and discuss some possible arguments supporting this hypothesis.


Sudden cardiac death due to triple myocardial bridging associated with atypical coronary topography.
Myocardial bridging (MB) is defined as the presence of an intramural course of a coronary artery, most likely caused by a defect in resorption of the musculature that encircles the epicardial arteries during morphogenesis. We present a case of the young man who died suddenly while playing professional football and whose cause of death was acute myocardial infarction associated with multiple myocardial bridges (1.8 cm on the anterior interventricular artery, 1.3 cm on the circumflex artery, and an intramyocardial trajectory of the posterior interventricular artery), and discuss the causes of death and possible consequences of this pathology.


Speech and Swallowing in Parkinson's Disease.
Dysarthria and dysphagia occur frequently in Parkinson's disease (PD). Reduced speech intelligibility is a significant functional limitation of dysarthria, and in the case of PD is likely related articulatory and phonatory impairment. Prosodically-based treatments show the most promise for addressing these deficits as well as for maximizing speech intelligibility. Communication-oriented strategies also may help to enhance mutual understanding between a speaker and listener. Dysphagia in PD can result in serious health issues, including aspiration pneumonia, malnutrition, and dehydration. Early identification of swallowing abnormalities is critical so as to minimize the impact of dysphagia on health status and quality of life. Feeding modifications, compensatory strategies, and therapeutic swallowing techniques all have a role in the management of dysphagia in PD.


Does cannabidiol reduce severe behavioural problems in children with intellectual disability? Study protocol for a pilot single-site phase I/II randomised placebo controlled trial.
Severe behavioural problems (SBPs) are a common contributor to morbidity and reduced quality of life in children with intellectual disability (ID). Current medication treatment for SBP is associated with a high risk of side effects. Innovative and safe interventions are urgently needed. Anecdotal reports and preliminary research suggest that medicinal cannabis may be effective in managing SBP in children with developmental disabilities. In particular, cannabidiol (CBD) may be a plausible and safe alternative to current medications. Families who are in urgent need of solutions are seeking cannabis for their ID children with SBP. However there is no evidence from randomised controlled trials to support the use of CBD for SBP. This pilot study aims to investigate the feasibility of conducting a randomised placebo-controlled trial of CBD to improve SBP in children with ID. This is a single-site, double-blind, parallel-group, randomised, placebo-controlled pilot study of 10 participants comparing 98% CBD oil with placebo in reducing SBP in children aged 8-16 years with ID. Eligible participants will be randomised 1:1 to receive either CBD 20 mg/kg/day or placebo for 8 weeks. Data will be collected regarding the feasibility and acceptability of all study components, including recruitment, drop-out rate, study visit attendance, protocol adherence and the time burden of parent questionnaires. Safety outcomes and adverse events will be recorded. All data will be reported using descriptive statistics. These data will inform the design of a full scale randomised controlled trial to evaluate the efficacy of CBD in this patient group. This protocol has received ethics approval from the Royal Children's Hospital ethics committee (Human Research Ethics Committee no. 38236). Results will be disseminated through peer-reviewed journals, professional networks, conferences and social media. ACTRN12618001852246.


Oncolytic HSV-Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition.
To examine the effect of oncolytic herpes simplex virus (oHSV) on NOTCH signaling in central nervous system tumors. Bioluminescence imaging, reverse phase protein array proteomics, fluorescence microscopy, reporter assays, and molecular biology approaches were used to evaluate NOTCH signaling. Orthotopic glioma-mouse models were utilized to evaluate effects in vivo. We have identified that herpes simplex virus-1 (HSV-1; oncolytic and wild-type)-infected glioma cells induce NOTCH signaling, from inside of infected cells into adjacent tumor cells (inside out signaling). This was canonical NOTCH signaling, which resulted in activation of RBPJ-dependent transcriptional activity that could be rescued with dnMAML. High-throughput screening of HSV-1-encoded cDNA and miRNA libraries further uncovered that HSV-1 miR-H16 induced NOTCH signaling. We further identified that factor inhibiting HIF-1 (FIH-1) is a direct target of miR-H16, and that FIH-1 downregulation by virus encoded miR-H16 induces NOTCH activity. FIH-1 binding to Mib1 has been reported, but this is the first report that shows FIH-1 sequester Mib1 to suppress NOTCH activation. We observed that FIH-1 degradation induced NOTCH ligand ubiquitination and NOTCH activity. REMBRANDT and The Cancer Genome Atlas data analysis also uncovered a significant negative regulation between FIH-1 and NOTCH. Furthermore, combination of oHSV with NOTCH-blocking gamma secretase inhibitor (GSI) had a therapeutic advantage in two different intracranial glioma models treated with oncolytic HSV, without affecting safety profile of the virus in vivo. To our knowledge this is the first report to identify impact of HSV-1 on NOTCH signaling and highlights the significance of combining oHSV and GSI for glioblastoma therapy.


Fournier's gangrene: experience of four cases.
Fournier's gangrene is an acute gangrenous inflammation of the male genitalia. In an 18-month period, four patients with Fournier's gangrene were treated at our hospital. Their ages ranged from 39 to 74 years (average 55.2). The presenting symptoms and signs included pain, swelling and necrosis of the scrotum and perineum, fever and jaundice were also noted. Three patients with the predisposing factor of urinary tract infection or perianal abscess recovered after surgical debridement and antibiotics treatment. Their hospital stay ranged between 13 and 50 days. One patient with diabetes, presenting severe septic shock at arrival, died one day after debridement. From the experience of our cases and review of the literature, early surgical debridement and antibiotics are mandatory for the treatment of Fournier's gangrene.


Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma.
Mutations have been described in the ataxia telangiectasia mutated (ATM) gene in small numbers of cases of lymphoid neoplasia. However, surveys of the ATM mutation status in lymphoma have been limited due to the large size (62 exons) and complex mutational spectrum of this gene. We have used microarray-based assays with 250,000 oligonucleotides to screen lymphomas from 120 patients for all possible ATM coding and splice junction mutations. The subtypes included were diffuse large B cell, mantle cell, immunoblastic large B cell, follicular, posttransplant lymphoproliferative disorder, and peripheral T cell lymphoma. We found the highest percentage of ATM mutations within the mantle cell (MCL) subtype (43%, 12 of 28 cases), followed by a lower level (10% of cases) in the other subtypes. A frame-shift ATM mutation was found in one peripheral T cell lymphoma patient. In six MCL cases examined, four ATM variants were due to somatic mutation in the tumor cells whereas two others seemed to be germ-line in origin. There was no difference in p53 mutation status in the ATM mutant and wild-type groups of MCL. There was no statistically significant difference in the median overall survival of patients with wild-type vs. mutated ATM in MCL. Additional mutational and functional analyses are needed to determine whether ATM mutations contribute to the development and progression of MCL or are just the consequence of genomic instability in MCL.


Predictive features of ligand-specific signaling through the estrogen receptor.
Some estrogen receptor-α (ERα)-targeted breast cancer therapies such as tamoxifen have tissue-selective or cell-specific activities, while others have similar activities in different cell types. To identify biophysical determinants of cell-specific signaling and breast cancer cell proliferation, we synthesized 241 ERα ligands based on 19 chemical scaffolds, and compared ligand response using quantitative bioassays for canonical ERα activities and X-ray crystallography. Ligands that regulate the dynamics and stability of the coactivator-binding site in the C-terminal ligand-binding domain, called activation function-2 (AF-2), showed similar activity profiles in different cell types. Such ligands induced breast cancer cell proliferation in a manner that was predicted by the canonical recruitment of the coactivators NCOA1/2/3 and induction of the GREB1 proliferative gene. For some ligand series, a single inter-atomic distance in the ligand-binding domain predicted their proliferative effects. In contrast, the N-terminal coactivator-binding site, activation function-1 (AF-1), determined cell-specific signaling induced by ligands that used alternate mechanisms to control cell proliferation. Thus, incorporating systems structural analyses with quantitative chemical biology reveals how ligands can achieve distinct allosteric signaling outcomes through ERα.


Development of a multilocus sequence typing tool for high-resolution subtyping and genetic structure characterization of Cryptosporidium ubiquitum.
Cryptosporidium ubiquitum is an emerging zoonotic pathogen in humans. Recently, a subtyping tool targeting the 60-kDa glycoprotein (gp60) gene was developed for C. ubiquitum, and identified six subtype families (XIIa-XIIf). In this study, we selected five genetic loci known to be polymorphic in C. hominis and C. parvum for the development of a multilocus subtyping tool for C. ubiquitum, including CP47 (cgd6_1590), MSC6-5 (cgd6_4290), cgd6_60, cgd2_3690, and cgd4_370. PCR primers for these targets were designed based on whole genome sequence data from C. ubiquitum. DNA sequence analyses of 24 C. ubiquitum specimens showed the presence of 18, 1, 5, 4, and 5 subtypes at the CP47, MSC6-5, cgd6_60, cgd2_3690, and cgd4_370 loci, respectively. Altogether, 18 multilocus sequence typing (MLST) subtypes were detected among the 19 specimens successfully sequenced at all polymorphic loci. Phylogenetic analyses of the MLST data indicated that the rodent subtype families of XIIe and XIIf were highly divergent from others, and the ruminant XIIa subtype family formed a monophyletic group genetically distant from other rodent subtype families XIIb, XIIc, and XIId. The latter showed no consistent grouping of specimens and formed one large cluster in phylogenetic analysis of concatenated multilocus sequences. This was supported by results of STRUCTURE and FST analyses, which further suggested that XIIa originated from one common ancestor whereas XIIb, XIIc, and XIId contained mixed ancestral types, reflecting a close relatedness of the three subtype families and the likely occurrence of genetic recombination among them. Thus, an MLST tool was developed for high-resolution subtyping of C. ubiquitum and results of preliminary characterizations of specimens from humans and animals supported the conclusion on the existence of ruminant and rodent-adapted C. ubiquitum groups.


Neurovascular coupling in the developing neonatal brain at rest.
The neonatal brain is an extremely dynamic organization undergoing essential development in terms of connectivity and function. Several functional imaging investigations of the developing brain have found neurovascular coupling (NVC) patterns that contrast with those observed in adults. These discrepancies are partly due to that NVC is still developing in the neonatal brain. To characterize the vascular response to spontaneous neuronal activations, a multiscale multimodal noninvasive approach combining simultaneous electrical, hemodynamic, and metabolic recordings has been developed for preterm infants. Our results demonstrate that the immature vascular network does not adopt a unique strategy to respond to spontaneous cortical activations. NVC takes on different forms in the same preterm infant during the same recording session in response to very similar types of neural activation. This includes (a) positive stereotyped hemodynamic responses (increases in HbO, decreases in HbR together with increases in rCBF and rCMRO2), (b) negative hemodynamic responses (increases in HbR, decreases in HbO together with decreases in rCBF and rCMRO2), and (c) Increases and decreases in both HbO-HbR and rCMRO2 together with no changes in rCBF. Age-related NVC maturation is demonstrated in preterm infants, which can contribute to a better understanding/prevention of cerebral hemodynamic risks in these infants.


Dupuytren's contracture: the deferred Z-plasty.
The technique of dissecting Dupuytren's contracture through a straight incision placed along the contracting band and deferring Z-plasty to be performed as a secondary procedure is safe, simple, and short and allows maximum skin viability and earliest mobilisation.


The role of calcium in stimulus-secretion coupling in excitable and non-excitable cells.
Secretion of vesicular contents by exocytosis is a common feature of excitable (neurones, chromaffin cells, beta cells) and non-excitable cells (platelets, neutrophils, mast cells). The simplistic view that the universal mechanism controlling secretion is elevation of [Ca2+]i--whatever the source of this second messenger may be--is no longer tenable in view of recent reports demonstrating secretion at basal or even reduced [Ca2+]i. It is nevertheless clear that in excitable cells an increase in [Ca2+]i is the triggering event that induces secretion. In non-excitable cells, secretion is presumably triggered by other second messengers, although [Ca2+]i appears to act as an important modulator of the rate of secretion. Conversely, these second messenger systems may serve a regulatory function in excitable cells. Given the relative importance of [Ca2+]i in the regulation of cellular functions in excitable and non-excitable cells, it is not surprising that several mechanisms are expressed in these cells to regulate intracellular calcium concentration. The major pathway for Ca2+ in excitable cells is by voltage-activated Ca2+ channels, but release of Ca2+ from intracellular stores, via second messengers, predominates in non-excitable cells, and may also be important in excitable cells. In addition, receptor-operated channels and second messenger-gated conductances may prove to be important. All of these pathways are subject to regulation by a variety of interactive second messenger systems, which provide necessary tuning for an appropriate control of intracellular calcium level.


An important cause of pes planus: the posterior tibial tendon dysfunction.
Posterior tibial tendon dysfunction (PTTD) is an important cause of acquired pes planus that frequently observed in adults. Factors that play a role in the development of PTTD such as age-related tendon degeneration, inflammatory arthritis, hypertension, diabetes mellitus, obesity, peritendinous injections and more rarely acute traumatic rupture of the tendon. PTT is the primary dynamic stabilizer of medial arch of the foot. Plantar flexion and inversion of the foot occurs with contraction of tibialis posterior tendon, and arch of the foot becomes elaveted while midtarsal joints are locked and midfoot-hindfoot sets as rigid. Thus, during the walk gastrocnemius muscle works more efficiently. If the PTT does not work in the order, other foot ligaments and joint capsule would be increasingly weak and than pes planus occurs. We present a 10-year-old female patient diagnosed as PTTD and conservative treatment with review of the current literature.


Association of Sociodemographic Factors on the Presentation and Management of Unilateral Vocal Fold Immobility.
To determine the association of social determinants of health (SDOH) on the presentation and management of unilateral vocal fold immobility (UVFI). Retrospective chart review of 207 adult UVFI patients evaluated at a tertiary-care hospital between 2018 and 2019 was performed. Sociodemographic factors including gender, median household income, preferred language, and insurance type were recorded. Confounding clinical factors including etiology of UVFI, Voice Handicap Index-10 (VHI-10) score, laryngoscopic findings, and intervention history were extracted from medical records. Multivariable logistic regression was performed using sociodemographic and clinical factors. Patient demographics and socioeconomic status were not associated with time to presentation. Patients presenting with glottic insufficiency and UVFI due to malignancy or recurrent laryngeal nerve (RLN) sacrifice had a shorter time to presentation. Higher household income was associated with greater number of interventions (p = 0.02), but neither income nor insurance type affected intervention type or timing. Female patients were less likely to undergo injection medialization laryngoplasty (odds ratio [OR] 0.25, p = 0.005). Older patients were more likely to undergo injection (OR 1.04, p = 0.027). Patients with large glottic gaps (OR 21.2, p = 0.014) and higher VHI-10 scores (OR 1.06, p = 0.047) were more likely to undergo surgery. Higher household income was associated with greater number of interventions and longer duration of care at a private tertiary-care hospital. RLN sacrifice, known malignancy, and glottic insufficiency significantly reduced the time to presentation. Type of intervention received was a complex interplay of both demographic and clinical factors. Large prospective studies should examine the role of SDOH in the presentation and management of UVFI. 4 Laryngoscope, 2023.


Influence of inter- and intramolecular hydrogen bonding on kemp decarboxylations from QM/MM simulations.
The Kemp decarboxylation reaction for benzisoxazole-3-carboxylic acid derivatives has been investigated using QM/MM calculations in protic and dipolar aprotic solvents. Aprotic solvents have been shown to accelerate the rates of reaction by 7-8 orders of magnitude over water; however, the inclusion of an internal hydrogen bond effectively inhibits the reaction with near solvent independence. The effects of solvation and intramolecular hydrogen bonding on the reactants, transition structures, and the rate of reaction are elucidated using two-dimensional potentials of mean force (PMF) derived from free energy perturbation calculations in Monte Carlo simulations (MC/FEP). Free energies of activation in six solvents have been computed to be in close agreement with experiment. Solute-solvent interaction energies show that poorer solvation of the reactant anion in the dipolar aprotic solvents is primarily responsible for the observed rate enhancements over protic media. In addition, a discrepancy for the experimental rate in chloroform has been studied in detail with the conclusion that ion-pairing between the reactant anion and tetramethylguanidinium counterion is responsible for the anomalously slow reaction rate. The overall quantitative success of the computations supports the present QM/MM/MC approach, which features PDDG/PM3 as the QM method.


Smad4 regulates claudin-1 expression in a transforming growth factor-beta-independent manner in colon cancer cells.
We have recently reported that the expression of a tight junction protein, claudin-1, is increased during colon carcinogenesis and particularly metastatic colorectal cancer. Manipulation of claudin-1 levels in colon cancer cells showed a positive correlation between claudin-1 expression and tumor growth and metastasis. However, the mechanisms underlying the increased claudin-1 expression in colorectal cancer remains unknown. The tumor suppressor Smad4 is a central intracellular signal transduction component of the transforming growth factor-beta (TGF-beta) family of cytokines. Loss of Smad4 protein expression is correlated with poor prognosis and is frequently observed in invasive and metastatic colorectal carcinoma. In the present study, we report an inverse relationship between Smad4 and claudin-1 expression in human colorectal carcinoma tumor samples and in human colon cancer cell lines. We found that the expression of Smad4 in Smad4-deficient but claudin-1-positive SW480 or HT29 colon cancer cell lines down-regulates claudin-1 expression through transcriptional repression by modulating beta-catenin/T-cell factor/lymphocyte enhancer factor activity. Furthermore, this Smad4-dependent inhibition of claudin-1 expression is independent of TGF-beta signaling because Smad4 expression alone is insufficient to restore TGF-beta signaling in the SW480 cells, and the selective TGF-beta receptor kinase inhibitor LY364947 did not prevent the Smad4 suppression of claudin-1 protein expression in either SW480 or HT29 cells. Taken together, these findings suggest a novel mechanism underlying Smad4 tumor-suppressive function through regulation of a potential metastatic modulator, claudin-1, in a TGF-beta-independent manner.


Trans-corneal reduction of anterior lens luxation in dogs with lens instability: a retrospective study of 19 dogs (2010-2013).
To evaluate the success rate and outcome of trans-corneal reduction of anterior lens luxation (TR-ALL) in dogs with lens instability. Nineteen dogs with anterior lens luxation. Medical records of dogs with anterior lens luxation (ALL) were reviewed: dogs were included if TR-ALL was performed followed by medical therapy in the form of topical 0.005% latanoprost ophthalmic solution. The duration of ALL, vision status, ophthalmic examination abnormalities, reason for performing TR-ALL and details of TR-ALL were recorded. Success rate for TR-ALL as well as postprocedure complications were also assessed. Twenty eyes from 19 dogs met the inclusion criteria. Median age was 6.5 years (0.3-15 years) and 47% were terriers (9/19). Successful TR-ALL was achieved in 85% of eyes (17/20); failure was attributed to posterior synechia or vitreous expansion. Short-term complications included corneal ulceration (2/20) and anterior uveitis (3/20); recurrence of anterior luxation occurred in only one dog. Median follow-up for visual eyes (11) following successful TR-ALL was 353 days (range of 1 to 1182 days). Vision was retained in 54.5% (6/11) of eyes with a median time to vision loss of 12 months as a result of glaucoma or presumed retinal detachment. Trans-corneal reduction of ALL provides a non-surgical alternative to intracapsular lens extraction (visual eyes) or enucleation (nonvisual eyes) in dogs. Long-term visual outcome of TR-ALL is comparable to intracapsular lens extraction for ALL.


[The comparison of the two Ottoman books of anatomy (17-19th centuries) with regard to the circulatory system].
17th and 19th centuries were particularly important for the development of the Ottoman medicine. Westernization which had already started in the 17th century continued along the 19th and the early 20th centuries. Turkish physicians began to contact with their European colleagues and in this period Latin medical terminology began to appear in the Ottoman medical literature. Sirvanli Semseddin Itaki's work of the 17th century, the Teşrihü'l Ebdan ve Tercüman-i Kibale-i Feylesufan, is the first illustrated Turkish manuscript of anatomy. The illustrations are qualified as developed examples, compared with the medical literature and knowledge of the period. In the 19th century, Sanizade Mehmet Ataullah Efendi (1771-1826) wrote a modern book of anatomy for the Ottoman medical doctors. Miyarü'l Etibba was one of the earliest printed medical books in Turkish. The second volume of Sanizade's Hamse, Miratü'l Ebdan fi Teşrih-i Azai'l Insan is the first printed Ottoman book on anatomy. In Usulü't-Tabia, the third volume of Hamse, the circulatory system is discussed. In this article, we studied the circulatory system described in Semseddin Itaki's Teşrih-ül Ebdan ve Tercüman-i Kibale-i Feylesufan and in Sanizade's Usulü't-Tabia and compared them.


Direct actions of ACTH on ovarian function of pseudopregnant rabbits.
The present study sought to assess whether the receptors for adrenocorticotropic hormone (ACTH), MC2R, and for glucocorticoid (GR) are expressed in corpora lutea (CL) of pseudopregnant rabbits and whether ACTH and cortisol exert any direct action on luteal function. By immunohistochemistry, positive reaction for MC2R and GR was detectable within luteal cells of CL. The MC2R mRNA levels were five-fold less abundant in day 9 than in day 4 CL (P<0.01). At both stages, ACTH agonist (ACTH 1-24) increased progesterone and prostaglandin (PG) E(2) (PGE(2)) (P<0.01), but reduced PGF(2α) releases (P<0.01) in vitro. ACTH 1-24 injection increased plasma cortisol levels within 4h (P<0.01), but decreased (P<0.01) progesterone 24h later and for the following two days. ACTH administration to estrous rabbits caused a transitory increase in blood progesterone concentrations (P<0.01). Daily injections of ACTH did not modify progesterone profile following ovulation. In conclusion, ACTH directly up-regulates CL progesterone production in vitro via MC2R, but indirectly hampers luteal function via cortisol-GR associated mechanism.


[The immunotropic properties of rifampicin and their correction].
The effect of rifampicin on antibody genesis depends on the dose, duration, and time of its administration in relation to the antigen, as well as on the character of immunosuppression. The antibiotic has no effect on delayed hypersensitivity and stimulates the activity of phagocytes, predominantly that of neutrophils. The effectiveness of rifampicin in experimental infection is maintained in treatment with cyclophosphane and azathioprine. When administered in combination with rifampicin and cytostatics methyluracil possesses a broader spectrum of immunostimulating activity than that of prodigiosin and levamisole.


Two new cysteine proteinases with specific expression patterns in mature and senescent tobacco (Nicotiana tabacum L.) leaves.
Cysteine proteinases are involved in various physiological and developmental processes in plants. Two cDNAs from senescent and non-senescent tobacco leaves were isolated with degenerate primers designed from conserved regions of plant senescence-associated cysteine proteinases using rapid amplification of cDNA ends (RACE). Both sequences encode papain-like cysteine proteinases: the 833 bp fragment (NtCP1) encoding a C-terminus partial sequence of a putative tobacco cysteine proteinase gene whereas the 1300 bp fragment (NtCP2) is a full-length cysteine proteinase. On the amino acid sequence level, NtCP1 has a high similarity with other senescence-associated cysteine proteinases. It is expressed only in senescent leaves. It is not induced in mature green leaves upon exposure to drought or heat. These results suggest that it might be a good developmental senescence marker in tobacco. By contrast, NtCP2 has a high similarity to KDEL-tailed cysteine proteinases and is expressed in mature green leaves. Both drought and heat decreased NtCP2 transcript abundance in mature green leaves. It is concluded that NtCP1 is a senescence-specific cysteine proteinase whereas NtCP2 fulfils roles in green leaves that might be similar to those of KDEL-tailed cysteine proteinases involved, for example, in programmed cell death.


Advances in cardiac processing software.
New software methods that incorporate iterative reconstruction, resolution recovery, and noise compensation now provide the ability to maintain or improve myocardial perfusion SPECT image quality with conventional sodium iodide cameras. Despite lower image counting statistics associated with significantly decreased injected radiopharmaceutical doses or shortened acquisition times or both, image quality is preserved or even improved compared with conventional processing methods. The ability to prescribe a desired myocardial count density by preselecting a SPECT acquisition time now avoids additional patient radiation exposure associated with "weight-based" dosing. More recent advancements, including temporal correlation among the gated perfusion frames and higher resolution SPECT acquisitions, hold promise to further improve image quality and diagnostic accuracy. Phase analysis of gated perfusion SPECT provides the ability to assess cardiac dyssynchrony and to select those patients who will most benefit from resynchronization therapy. In combination with the higher counting statistics afforded by the new solid-state dedicated cardiac cameras, these software advancements allow for even further decreased patient radiation doses or acquisition times or both. List-mode software allows for refinement of myocardial perfusion SPECT by interrogating particular data from selected cardiac cycles. Rejection of frames degraded by arrhythmic cardiac cycles or excessive extracardiac uptake can be excluded for reconstruction. Respiratory gating, which diminishes cardiac motion and potentially decreases diaphragmatic attenuation, has been demonstrated to improve diagnostic specificity. With high-count first-pass list-mode acquisitions at rest and during pharmacologic vasodilatation, it may be possible to measure global and regional myocardial perfusion reserve to more accurately diagnose coronary artery disease and avoid false-negative studies owing to balanced ischemia.


The subiculum role on learning and memory tasks using rats and mice: A scoping review.
This scoping review aimed to systematically identify and summarize data related to subiculum involvement in learning and memory behavioral tasks in rats and mice. Following a systematic strategy based on PICO and PRISMA guidelines, we searched five indexed databases (PubMed, Web of Science, EMBASE, Scopus, and PsycInfo) using a standardized search strategy to identify peer-reviewed articles published in English (pre-registration: osf.io/hm5ea). We identified 31 articles investigating the role of the subiculum in spatial, working, and recognition memories (n = 11), memories related to addiction models (n = 9), aversive memories (n = 7), and memories related to appetitive learning (n = 5). We highlight a dissociation in the dorsoventral axis of the subiculum with many studies exploring the ventral subiculum (n = 21) but only a few exploring the dorsal one (n = 10). We also observe the necessity of more data including mice, female animals, genetic tools, and better statistical approaches for replication purposes and research refinement. These findings provide a broad framework of the subiculum involvement in learning and memory, showing essential questions that can be explored by further studies.


Research Note: Muscle hypertrophy is associated with reversed sexual dimorphism in body size of quail.
Sexual dimorphism is phenotypic differences between males and females in the same species. In general, males in most animals are larger than females at the same age, however, in quail, females have a larger body size with greater muscle mass than males. To understand what characteristics in muscle growth play roles in reversed sexual dimorphism in quail, the weights and the characteristics of the pectoralis major and gastrocnemius muscles (PM and GM, respectively) of male and female quail were compared in the current study. The data showed that 15-wk-old female quail have significantly heavier bodies, and PM and GM weights compared to male quail (1.27-folds, 1.29-folds, and 1.16-folds, respectively). To compare muscle characteristics such as hypertrophy (increased size) and hyperplasia (increased cell number), the PM and GM were stained using hematoxylin and eosin, and then histological characteristics such as total cross-sectional area (CSA), number and size of myofibers, and muscle bundle of the muscles were measured and analyzed. In both PM and GM, there were no differences in total numbers of myofibers and muscle bundles as well as the average numbers of myofibers per bundle between sexes. However, the sizes of myofiber and the bundle were significantly increased in female compared to male (1.33-folds and 1.28-folds in PM, and both 1.23-folds in GM, respectively). The findings of the current study suggest that muscle hypertrophy in female quail, not hyperplasia, can be attributed to the sexual dimorphism in quail size.


Non-suicidal self-injury in trans people: associations with psychological symptoms, victimization, interpersonal functioning, and perceived social support.
There is a paucity of systematic research in the area of non-suicidal self-injury (NSSI) in trans people. The aim of this study was to investigate the prevalence of NSSI in trans people and the associations with intra- and interpersonal problems. Participants were 155 untreated individuals with a diagnosis of transsexualism (according to International Classification of Disease-10 criteria) attending a national gender identity clinic. All participants completed the Self-Injury Questionnaire, the Symptom Checklist-90-Revised, the Rosenberg Self-Esteem Scale, the Hamburg Body Drawing Scale, the Experiences of Transphobia Scale, the Inventory of Interpersonal Problems-32, and the Multidimensional Scale of Perceived Social Support. The sample consisted of 66.5% trans women and 33.5% trans men and 36.8% of them had a history of engaging in NSSI. The prevalence of NSSI was significantly higher in trans men (57.7%) compared with trans women (26.2%). Trans individuals with NSSI reported more psychological and interpersonal problems and perceived less social support compared with trans individuals without NSSI. Moreover, the probability of having experienced physical harassment related to being trans was highest in trans women with NSSI (compared with those without NSSI). The study found that with respect to psychological symptoms, trans women reported significantly more intrapersonal and interpersonal symptoms compared with trans men. Finally, the results of the regression analysis showed that the probability of engaging in NSSI by trans individuals was significantly positively related to a younger age, being trans male, and reporting more psychological symptoms. The high levels of NSSI behavior and its association with interpersonal and interpersonal difficulties and lack of social support need to be taken into consideration when assessing trans individuals. The effect of cross-sex hormones and sex reassignment surgery on psychological functioning, including NSSI behavior, as part of the transitional journey of trans individuals should be explored in future studies.


[Initial experiences in the treatment of changes in the anterior eye segment with the neodymium:YAG laser].
The present paper reports the first results with the Meditec OPL-3 neodymium:YAG laser (Rodenstock, Munich). The YAG laser is a pulsed laser, the biological effects of which are based on the formation of plasma at its focal point. Plasma formation induces a rapid explosion-like expansion of the tissue. This effect can be used to sever opaque structures of the refractive media of the eye, such as secondary cataracts, membranes or strands. The paper summarizes the results of the first 80 consecutive cases treated with the laser. The surgical procedure is described in detail. Visual acuity improved instantaneously in all cases in which no concomitant eye pathology (e.g., corneal or macular changes) existed. Complications consisted in the development of postoperative inflammatory reactions and increases in intraocular pressure, and responded well to corticosteroids and beta-blockers or Diamox. The development of the neodymium:YAG laser has considerably advanced our therapeutic possibilities.


Multilevel models for multiple-baseline data: modeling across-participant variation in autocorrelation and residual variance.
Multilevel models (MLM) have been used as a method for analyzing multiple-baseline single-case data. However, some concerns can be raised because the models that have been used assume that the Level-1 error covariance matrix is the same for all participants. The purpose of this study was to extend the application of MLM of single-case data in order to accommodate across-participant variation in the Level-1 residual variance and autocorrelation. This more general model was then used in the analysis of single-case data sets to illustrate the method, to estimate the degree to which the autocorrelation and residual variances differed across participants, and to examine whether inferences about treatment effects were sensitive to whether or not the Level-1 error covariance matrix was allowed to vary across participants. The results from the analyses of five published studies showed that when the Level-1 error covariance matrix was allowed to vary across participants, some relatively large differences in autocorrelation estimates and error variance estimates emerged. The changes in modeling the variance structure did not change the conclusions about which fixed effects were statistically significant in most of the studies, but there was one exception. The fit indices did not consistently support selecting either the more complex covariance structure, which allowed the covariance parameters to vary across participants, or the simpler covariance structure. Given the uncertainty in model specification that may arise when modeling single-case data, researchers should consider conducting sensitivity analyses to examine the degree to which their conclusions are sensitive to modeling choices.


Direct determination of gibberellic acid in tomato and fruit by using photochemically induced fluorescence.
A simple, sensitive method for determining gibberellic acid based on photochemically induced fluorescence detection was developed to determine this plant growth regulator in a technical formulation, tomato, and fruit samples. The principle for the determination is the photochemical reactivity of the gibberellic acid, being consistent with the occurrence of photoaromatization and photochemical dimerization with loss of carbon dioxide, and with the likely formation of various fluorescent photoproducts. Six min of UV (mainly at 253.7 nm) irradiation in a solution containing 50% (v/v) methanol and buffer at pH 5 provided the best results. The calibration curve was linear over the concentration range 50-150 ng mL(-1), and the limit of detection was 1.7 ng mL(-1). The method is useful to determine gibberellic acid in samples with background fluorescence such as plum and tomato without the need for labor-intensive preparation as a result of UV irradiation suppressing the fluorescent background.


individual variation in sleep quality and duration is related to cerebral mu opioid receptor binding potential during tonic laboratory pain in healthy subjects.
Although poor sleep is a consequence of pain, sleep disturbance reciprocally induces hyperalgesia and exacerbates clinical pain. Conceptual models of chronic pain implicate dysfunctional supraspinal pain processing mechanisms, mediated in part by endogenous opioid peptides. Our preliminary work indicates that sleep disruption impairs psychophysical measures of descending pain modulation, but few studies have investigated whether insufficient sleep may be associated with alterations in endogenous opioid systems. This preliminary, exploratory investigation sought to examine the relationship between sleep and functioning of the cerebral mu opioid system during the experience of pain in healthy participants. Twelve healthy volunteers participated in a 90-minute positron emission tomography imaging scan using [11C]Carfentanil, a mu opioid receptors agonist. During the session, pain responses to a 10% topical capsaicin cream were continuously rated on a 0-100 scale. Participants also completed the Pittsburgh Sleep Quality Index (PSQI). Poor sleep quality (PSQI) was positively and significantly associated with greater binding potential (BP) in regions within the frontal lobes. In addition, sleep duration was negatively associated with BP in these areas as well as the temporal lobe and anterior cingulate. These findings suggest that poor sleep quality and short sleep duration are associated with endogenous opioid activity in these brain regions during the application of a noxious stimulus. Elucidating the role of the endogenous opioid system in mediating some of the associations between sleep and pain could significantly improve our understanding of the pathophysiology of chronic pain and might advance clinical practice by suggesting interventions that could buffer the adverse effects of poor sleep on pain.


Predicting acoustic orientation in complex real-world environments.
Animals have to accomplish several tasks in their lifetime, such as finding food and mates and avoiding predators. Animals that locate these using sound need to detect, recognize and localize appropriate acoustic objects in their environment, typically in noisy, non-ideal conditions. Quantitative models attempting to explain or predict animal behaviour should be able to accurately simulate behaviour in such complex, real-world conditions. Female crickets locate potential mates in choruses of simultaneously calling males. In the present study, we have tested field cricket acoustic orientation behaviour in complex acoustic conditions in the field and also successfully predicted female orientation and paths under these conditions using a simulation model based on auditory physiology. Such simulation models can provide powerful tools to predict and dissect patterns of behaviour in complex, natural environments.


Effects of aldicarb and neonicotinoid seed treatments on twospotted spider mite on cotton.
Twelve field experiments and one laboratory experiment were conducted to determine the effects of furrow applied aldicarb and seed treatments of thiamethoxam, imidacloprid, Avicta (thiamethoxam + abamectin), Aeris (imidacloprid + thiodicarb), and acephate on twospotted spider mite, Tetranychus urticae Koch, on cotton, Cossypium hirsutum L. For the field experiments, data were pooled across all experiments for analysis. Aeris, thiamethoxam, and imidacloprid treatments resulted in twospotted spider mite densities greater than those in the untreated check, aldicarb, and acephate treatments. However, cotton treated with Avicta (thiamethoxam + abamectin) had 34% fewer mites than other neonicotinoid seed treatments when infestations occurred near cotyledon stage. Untreated check and aldicarb treatments had the lowest mite densities. Only aldicarb reduced mite densities below that in the untreated check. In a laboratory trial, the fecundity of twospotted spider mite was measured. While neonicotinoid seed treatments increased mite densities in the field, they did not increase fecundity in the laboratory experiment. Foliar applied thiamethoxam slightly elevated average fecundity in the laboratory experiment. Increased use of neonicotinoid seed treatments instead of furrow applied aldicarb is likely at least partly responsible for recent increased twospotted spider mite infestations in seedling cotton across the mid-south.


[Minimally invasive surgery for dacryostenosis: modern trends].
The article presents the results of a monocentric randomized open prospective study conducted from 2008 to 2013. Lacrimal intubation with Mini-Monoka and Monoka silicone stents (mono- or bicanalicular) or with SRS and Ritleng ("FCI", France) stents for dacryostenosis of different localization was performed in 151 patients (203 eyes). The follow-up period was 12 months after the extubation. Patient examination and monitoring included collection of subjective Munk scores for epiphora, lacrimal scintigraphy and bulbar hyperemia evaluation. Though all interventions were proved to be effective, the authors came to the conclusion that, bicanalicular Mini-Monoka and Monoka stents were associated with fewer complications as compared with bicanalicular SRS and Ritleng stents.


[Swelling of the finger as initial manifestation of sarcoidosis].
An extensive differential diagnosis exists for swelling of the fingers. One of the rare causes of such a swelling is a multisystem disorder called sarcoidosis. We describe a 40-year-old female patient who was first seen at our outpatient clinic with a painless swelling of the middle phalanx of her right middle finger. The diagnosis initially made was enchondroma, which was treated conservatively. Thirteen years later, the patient returned with pain and progressive swelling of this same finger. Physical examination and imaging revealed a giant-cell tumour of the tendon sheath, which was excised. The diagnosis of sarcoidosis was made after histological analysis. The initial manifestation of sarcoidosis is rarely observed in bone and soft tissue. For this reason, symptoms arising from such tissues will not always lead to the consideration of this diagnosis. The typical radiological abnormalities of bone combined with swelling of soft tissue should, however, give rise to the consideration of this diagnosis.


Reconstructive rhinoplasty for the lower two-thirds of the nose.
A general format has been developed and used for reconstruction of the lower two-thirds of the nose in patients retaining some septum who have a low forehead. The lining above the alae comes from strategic local flaps, while the alar lining and most of the columella are produced by a pair of nasolabial flaps. Support is provided by the residual septum (sometimes advance), and by a later costal chondroperichondrial hinge graft. The cover comes from a "headless" gull-shaped, forehead flap.


PCDD and PCDF exposures among fishing community through intake of fish and shellfish from the Straits of Malacca.
Exposure to PCDD/PCDF (dioxin and furan) through consumption of fish and shellfish is closely related to the occurrence of skin diseases, such as chloracne and hyperpigmentation. This study aimed to determine the exposure of PCDD/PCDF and its congeners in fish and shellfish obtained from different regions of the Straits of Malacca among the fishing community. The risk of fish and shellfish consumption and exposure to PCDD/PCDF among fishermen living in coastal areas of the Straits were evaluated based on a cross-sectional study involving face to face interviews, blood pressure and anthropometric measurements, and administration of food frequency questionnaires (FFQ). Skin examination was done by a dermatologist after the interview session. Determination of 17 congeners of PCDD/PCDF in 48 composite samples of fish and shellfish was performed based on HRGC/HRMS analysis. The total PCDD/PCDF in the seafood samples ranged from 0.12 to 1.24 pg WHO-TEQ/g fresh weight (4.6-21.8 pg WHO-TEQ/g fat). No significant difference found for the concentrations of PCDD/PCDF between the same types of seafood samples obtained from the three different regions. The concentrations of the most potent congener, 2,3,7,8-TCDD in the seafood samples ranged from 0.01 to 0.11 pg WHO-TEQ/g FW (1.9 pg WHO-TEQ/g fat). A positive moderate correlation was found between the fat contents and concentrations of PCDD/PCDF determined in the seafood samples. The total PCDD/PCDF in all seafood samples were below the 1 pg WHO-TEQ/g fresh weight, with the exception of grey eel-catfish. The respondents had consumed fish and shellfish with the amounts ranging between 2.02 g and 44.06 g per person per day. The total PCDD/PCDF exposures through consumption of fish and shellfish among the respondents were between 0.01 and 0.16 pg WHO-TEQ/kg BW/day. With regard to the two PCDD/PCDF-related skin diseases, no chloracne case was found among the respondents, but 2.2% of the respondents were diagnosed to have hyperpigmentation. Intake of a moderate amount of fish and shellfish from the area is safe and does not pose a risk for skin diseases. An over-consumption of seafood from the potentially polluted area of the Straits should be monitored in future.


The prognostic value of the plasma N-terminal pro-brain natriuretic peptide level on all-cause death and major cardiovascular events in a community-based population.
Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value for patients with cardiovascular disease, chronic kidney disease, etc, the prognostic significance of NT-proBNP levels in the general population has not been established. The aim of this study was to evaluate the clinical significance of NT-proBNP in a community population. This is a community-based prospective survey of residents from two communities in Beijing conducted for a routine health status checkup. Out of 1,860 individuals who were eligible for inclusion from 2007 to 2009, 1,499 completed a follow-up and were assessed for the prognostic value of NT-proBNP in 2013. A questionnaire was used for end point events. Anthropometry and blood pressure were measured. Plasma NT-proBNP, creatinine, lipids, and glucose were determined. A total of 1,499 subjects with complete data were included in the analysis. Participants were divided into four groups according to baseline NT-proBNP levels (quartile 1, <19.8 pg/mL; quartile 2, 19.8-41.6 pg/mL; quartile 3, 41.7-81.8 pg/mL; quartile 4, ≥81.9 pg/mL). During a median 4.8-year follow-up period, the all-cause mortality rate rose from 0.8% in the lowest concentration NT-proBNP group (<19.8 pg/mL) to 7.8% in the highest NT-proBNP group (≥81.9 pg/mL; P<0.001). The incidence of major adverse cardiovascular events (MACEs) increased from 3.1% in the lowest NT-proBNP group to 18.9% in the highest group (P<0.001). Individuals in the highest NT-proBNP group (≥81.9 pg/mL) were associated with higher risk of all-cause death and MACEs compared with the lowest NT-proBNP group using Kaplan-Meier survival curves and the Cox proportional hazard model after adjusting for age, sex, and traditional risk factors. The plasma NT-proBNP level is a strong and independent prognosis factor for all-cause death and MACEs in the community population. The NT-proBNP cut-point for the prognostic value remains to be further studied. NT-proBNP is a strong and independent prognostic factor for all-cause death and MACEs in individuals older than 65 years and MACEs in individuals younger than 65 years.


Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis.
Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.


Cutaneous malignant lymphomas. A clinicopathologic study of thirty-seven cases.
Clinical and histological findings in 37 cases of cutaneous lymphomas other than mycosis fungoides and Sezary syndrome were investigated; there were 31 in adults and 6 in children. Cutaneous lesions were the first manifestations of the diseases in all cases, and they appeared mostly as tumors or nodules. Cytomorphologically, about a half of the cases showed proliferations of large cleaved, non-cleaved cells or immunoblasts (Group I). Eight cases showed a polymorphous appearance containing convoluted cells of various size (Group II). Five cases in children demonstrated monomorphous proliferation of uniform-sized lymphoblasts (Group III). The cytologic findings in 6 cases did not fit into any lymphoid groups (Group IV). The clinical findings observed in each group were reviewed and compared. Follow-up study revealed that the prognosis of Group I was the poorest among the four groups.


The reliability of Michaelis constants and maximum velocities estimated by using the integrated Michaelis-Menten equation.
1. Experimental progress curves were simulated for a reaction obeying Michaelis-Menten kinetics. 2. K(m) and V were estimated (a) by fitting the integrated Michaelis-Menten equation to the progress curves, and (b) from the initial slopes of the curves (i.e. from initial velocities). 3. The integrated equation could not be fitted successfully by a non-linear method, so it was transformed and fitted by a linear method. 4. Provided that the initial substrate concentration was greater than K(m) and the data were precise enough, the integrated equation gave parameter estimates which were unbiased and as reliable as those derived from initial velocities although based on fewer experiments. 5. The integrated equation could be used for progress curves of unknown origin.


A live vaccine against pertussis.
Animal experiments have shown that oral administration of live Bordetella pertussis induces a protective immune response. The biological properties of a nonpathogenic Bordetella pertussis strain, its toxicity and immunogenicity in mice were investigated. Comparative studies of the intraperitoneal and the oral route of immunization have shown that there was high mortality following intraperitoneal administration of the highest dose, whereas none of the doses of vaccine given orally led to appreciably higher mortality than that observed in control animals. The oral method of immunization when employing a stable, non-toxic, live vaccine strain, may be of value for women of child-bearing age, pregnant women, and for pediatric and nursing personnel exposed to the risk of pertussis infection. Infants may benefit by transplacentally conferred protection as well as being actively immunized at an early age after birth.


The structure of anticapsin, a new biologically active metabolite of Streptomyces griseoplanus.
1. Physical and analytical data obtained on crystalline anticapsin indicated the empirical formula C(9)H(13)NO(4). Spectral data (u.v., i.r. and proton magnetic resonance) and formation of l-tyrosine on hydrolysis revealed the functionalities and carbon skeleton of the new epoxy keto amino acid. 2. The optical properties of anticapsin (optical rotatory dispersion and circular dichroism) permitted assignment of absolute configuration to the new metabolite. 3. Treatment of anticapsin with hot methanolic hydrochloric acid followed by acetylation gave C(18)H(19)NO(5), the alpha-alkoxycyclohexenone derivative. Analysis of the nuclear-magnetic-resonance and mass spectra of the latter allowed its structure to be determined and confirmed the assigned structure of anticapsin.


Prostaglandin E1-induced vasorelaxation in porcine coronary arteries.
The mechanism of prostaglandin E1 (PGE1)-induced vasorelaxation was studied in the porcine left anterior descending artery (diameter = 2.0-3.0 mm) and its branches (diameter = 0.6-1.0 mm). In the large coronary arteries, PGE1 increased the basal tone at concentrations from 10(-8) to 3 x 10(-7) M and decreased the tone at concentrations above 3 x 10(-7) M. However, in the small coronary arteries, PGE1 did not affect the basal tone at concentrations below 3 x 10(-6) M and evoked only relaxation at above 10(-5) M. PGE1 caused dose-dependent relaxation of vessels previously contracted by prostaglandin F2 alpha or endothelin-1 at concentrations above 10(-7) M in large coronary arteries and above 10(-8) M in small coronary arteries. Removal of the endothelium did not influence the relaxant response to PGE1 of either type of artery. In addition, 10(-4) M aspirin did not influence the PGE1-induced vasorelaxation of large and small coronary arteries. However, treatment with 5 x 10(-6) M ouabain or partial replacement of Na+ with Li+ (Na+ concentration, 25 mEq/l) significantly attenuated the relaxant response to PGE1 in large and small coronary arteries. These results indicate that the responsiveness of large and small coronary arteries to PGE1 differs in the pig and that the electrogenic Na+ pump has a primary role in the relaxant effect of PGE1 on both small and large arteries.


Vitamin D deficiency - a possible link between osteoporosis and metabolic syndrome.
The aim of our study was to evaluate the relationship between bone mineral density (examined by DXA - dual energy x-ray absorptiometry), vitamin D3 levels and the signs of metabolic syndrome. We examined 55 subjects (37 women, 18 men, age median 67.8 years) with no history of osteoporosis, suffering from metabolic syndrome (defined as abdominal obesity and more than 2 of other components - arterial hypertension, dyslipidemia and diabetes mellitus or impaired glucose tolerance, according to IDF, 2006). Osteoporosis (T-score less than - 2.5) was found in 32.7 % (15 women and 3 men) and osteopenia (T-score between - 1.5 and - 2.5) in 29 % (13 women and 3 men) of patients. We observed a negative correlation between BMI and fat percentage (examined by DXA) and vitamin D3 levels. Low concentration of vitamin D3 was found in 90 % of patients with median 19.36 ug/l (64 % measured in winter, 36 % in summer, no relationship between vitamin D3 levels and season). We also observed a negative correlation between the low concentration of vitamin D3 and presence of diabetes mellitus as a part of metabolic syndrome. The link between osteoporosis and metabolic syndrome could influence the therapeutic approach in both disorders and vitamin D supplementation may play an important role in prevention of these severe conditions (Tab. 5, Fig. 1, Ref. 29).


Jakartans' Perceptions of Health Care Services.
Health Care Services (HCSs) should implement ongoing innovation and continuously improve their quality. However, in evaluating the quality of HCSs, too little attention has been given to the experience of the users concerning the acquired services. This study focused on how the community values the current services in order to improve HCSs in Indonesia, especially in Jakarta. Four focus group discussions were conducted among 45 community members in the Grogol Petamburan sub-district, in Jakarta. Participants were recruited using a convenience sampling and the data were analyzed using a combination of human coding and NVivo-12. Overall, we found that participants had a negative view of the government-mandated Community Health Centers (CHCs) and they preferred to visit private clinics and hospitals over the CHCs. Participants associated CHCs with unfriendly staffs, longer waiting times, shorter opening hours, and crowded visitors. At the same time, participants had a positive view on the affordability of the CHCs. Additionally, we found the reasoning of Jakartans' (i.e., the citizens of Jakarta city) on using self- and traditional treatments before visiting HCSs and they also expressed the need for psychological services at CHCs. The discussion focuses on the results as feedback on how the government and health care providers may facilitate the community's needs in providing HCSs in Indonesia, especially Jakarta. In brief, we recommend the policy-makers to improve the hospitality of the staff members and the quality of the medical equipment; also, to provide psychological services at CHCs. These efforts need to be done while paying more attention to the cultural aspects of medicinal uses.


Treatment of highland frogs from the two-legged stage with homeopathically prepared thyroxin (10-11 - 10-21).
The influence of moderately diluted, agitated, i.e., homeopathically prepared, thyroxin solutions (10-11 - 10-21, final concentration in the basin water 0.6 10-15 - 0.6 10-25 parts by weight after the first application) on metamorphosis in highland Rana temporaria from the two-legged stage was studied. In accordance with the homeopathic idea of effects of specially prepared dilutions being inverse to those of their mother substances, animals were treated either with thyroxin 10-11 - 10-21 or analogously prepared blank solution (water). Development was monitored by documenting the number of animals that had entered the four-legged stage. It has been found that animals treated with the thyroxin solutions metamorphosed more slowly than the control animals, i.e., the effect of the homeopathically prepared thyroxin was opposed to the usual effect of molecular thyroxin. The number of test animals that reached the four-legged stage at defined points in time was smaller (2-13.5%) in the group treated with homeopathically prepared thyroxin at the points in time, compared to control. The results in this study sustain the previous multiresearcher findings that show that diluted homeopathically prepared thyroxin is able to slow down metamorphosis of R. temporaria.


Yangsaeng and Health Related Quality of Life (HRQOL) in Middle Aged Women.
The purpose of this study was to investigate the relationship of Yangsaeng and HRQOL in middle aged women. Yangsaeng as a traditional health care regimen for the promotion of health and prevention of illness by means of specific principles and methods, which purpose was to improve longevity and healthy life. The subjects of this study were 200 middle aged women in Korea. Data were collected by using a self-reported questionnaire and analyzed through descriptive statistics, Pearson's correlation coefficient, t-test, ANOVA and multiple linear regression. There was statistically significant difference in Yangsaeng according to age, stress and working hours. There were significant differences in HRQOL according to stress and working hours. The relationship between Yangsaeng and HRQOL had a significant positive correlation. Mind and diet Yangsaeng, christianity, and working hours were found to be significant predictors (24.6%) of HRQOL. To promote HRQOL of middle aged women, the nurse should focus on the factors identified in this study when she develop nursing intervention programs for health promotion.


Phenotypic overlap of Ehlers-Danlos syndrome types IV and VIII.
An 18-year-old Caucasian woman has been followed since age 12 years for Ehlers-Danlos syndrome (EDS) with easy bruisability and "cigarette paper scars." Her chief complaint at age 17 years was tooth mobility, especially in the anterior mandible, necessitating the removal of the four incisors. Initial biochemical analysis of cultured skin fibroblasts indicated the presence of pepsin-sensitive type III collagen. Subsequent analysis of cultured skin fibroblasts by the same laboratory and another laboratory found no abnormality in the type III collagen with or without protease treatment. This is in distinction to the finding of abnormal type III collagen in the only two reported patients with EDS and early-onset periodontitis who have had collagen analyses. One of them was diagnosed as EDS type IV and the other as EDS type VIII, although the defects of type III collagen were consistent with EDS type IV. The defect in type III collagen in some patients with early periodontitis and the considerable overlap of the clinical manifestations of EDS types IV and VIII point out the need for further studies of collagen formation and maturation in any patient who has early periodontitis and who has been classified with EDS type IV or VIII.


In vivo pyruvate detected by MR spectroscopy in neonatal pyruvate dehydrogenase deficiency.
We present a unique finding of an elevated level of pyruvate at 2.37 ppm revealed by in vivo MR spectroscopy of a female neonate. Low fibroblast pyruvate dehydrogenase (PDH) complex activity subsequently confirmed a diagnosis of PDH deficiency. Abnormalities of brain development consistent with PDH deficiency were also evident on fetal and postnatal MR images. To our knowledge, this is the first report of pyruvate being shown in vivo in a child and the first report of MR spectroscopy aiding in the diagnosis of inborn error in pyruvate metabolism before confirmation by conventional enzymatic testing. This finding has potential implications for earlier diagnosis in patients with defects in mitochondrial metabolism.


Nanoscale Raman Characterization of a 2D Semiconductor Lateral Heterostructure Interface.
The nature of the interface in lateral heterostructures of 2D monolayer semiconductors including its composition, size, and heterogeneity critically impacts the functionalities it engenders on the 2D system for next-generation optoelectronics. Here, we use tip-enhanced Raman scattering (TERS) to characterize the interface in a single-layer MoS2/WS2 lateral heterostructure with a spatial resolution of 50 nm. Resonant and nonresonant TERS spectroscopies reveal that the interface is alloyed with a size that varies over an order of magnitude─from 50 to 600 nm─within a single crystallite. Nanoscale imaging of the continuous interfacial evolution of the resonant and nonresonant Raman spectra enables the deconvolution of defect activation, resonant enhancement, and material composition for several vibrational modes in single-layer MoS2, MoxW1-xS2, and WS2. The results demonstrate the capabilities of nanoscale TERS spectroscopy to elucidate macroscopic structure-property relationships in 2D materials and to characterize lateral interfaces of 2D systems on length scales that are imperative for devices.


[Potentially pathogenic changes in red blood cells during their storage].
Blood fractionation and storage improve the availability of blood products, e.g., packed red blood cells (RBCs) for transfusion. But the following question appears: how long-stored RBCs are safe and effective? In many clinical retrospective studies authors indicated risk of transfusion of stored RBCs, especially in critically ill patients eg. with acute myocardial infarction syndrome. They observed higher frequency of mortality, morbidity, infections, renal and lung failure, inflammation and thrombosis when RBC units were long-stored and non-leucoreduced than when they were fresh and leucoreduced. Responsible mechanisms are unknown but some factors are suspected eg.: RBCs do not deliver oxygen, because they have low concentration of ATP and 2.3 DPG and their shape changes. Also cytokines, enzymes and ions (K, Ca) from white blood cells (WBCs) can influence RBCs and transfused patients. Changes involve some membrane molecules associated with adhesion, oxygen transport, complement regulation during the storage of RBCs. It is interesting how the long-period storage and presence of WBCs can influence the membrane surface of RBCs and then their biological functions. Proposed study can improve our knowledge about changes in RBCs during their storage and then may be safety of blood transfusion.


Enhancement of motor skill learning by a combination of ideal model-observation and self-observation.
[Purpose] In sports physical therapy, video of a patient's movement or of a skilled model's movement has been used as observational learning methods for injury prevention and movement modification. Positive effects of model video observation have been reported. This study aimed to clarify the effect on motor skill learning using a combination of model-observation and self-observation, which is thought to act as an enhanced method for active error detection by comparing model-observation and self-observation alone for acquisition of correct sports movement. [Subjects and Methods] Forty-five healthy females were randomly allocated into three groups comprising model- and self-observation, model-observation, and self-observation. The motor task performed was a half golf swing using an elastic club. Shoulder grip angle between both shoulder lines and the acromia grip strength were measured as an index of body rotation using a three-dimensional motion analyzer. Change in the shoulder grip angle in the three groups was analyzed at pre-, immediate delayed retention, and delayed retention tests. [Results] A significant difference in shoulder grip angle was observed among the three groups for the immediate delayed retention test. The combined model and self-observation group had a value closer to 90 degrees compared to the other two groups. [Conclusion] Observation combining model and self-observation exerted a positive effect on short-term motor skill learning.


Monitoring Microcirculation: Utility and Barriers - A Point-of-View Review.
Microcirculation is a particular organ of the cardiovascular system. The goal of this narrative review is a critical reappraisal of the present knowledge of microcirculation monitoring, mainly focused on the videomicroscopic evaluation of sublingual microcirculation in critically ill patients. We discuss the technological developments in handheld videomicroscopy, which have resulted in adequate tools for the bedside monitoring of microcirculation. By means of these techniques, a large body of evidence has been acquired about the role of microcirculation in the pathophysiological mechanisms of shock, especially septic shock. We review the characteristics of sublingual microcirculation in septic shock, which mainly consist in a decrease in the perfused vascular density secondary to a reduction in the proportion of perfused vessels along with a high heterogeneity in perfusion. Even in patients with high cardiac output, red blood cell velocity is decreased. Thus, hyperdynamic flow is absent in the septic microcirculation. We also discuss the dissociation between microcirculation and systemic hemodynamics, particularly after shock resuscitation, and the different behavior among microvascular beds. In addition, we briefly comment the effects of some treatments on microcirculation. Despite the fact that sublingual microcirculation arises as a valuable goal for the resuscitation in critically ill patients, significant barriers remain present for its clinical application. Most of them are related to difficulties in video acquisition and analysis. We comprehensively analyzed these shortcomings. Unfortunately, a simpler approach, such as the central venous minus arterial PCO2 difference, is a misleading surrogate for sublingual microcirculation. As conclusion, the monitoring of sublingual microcirculation is an appealing method for monitoring critically ill patients. Nevertheless, the lack of controlled studies showing benefits in terms of outcome, as well as technical limitations for its clinical implementation, render this technique mainly as a research tool.


Mannosylated lipid nano-emulsions loaded with lycorine-oleic acid ionic complex for tumor cell-specific delivery.
This study was to prepare a mannosylated lycorine lipid nano-emulsion formulation (M-LYC-OA-LNEs) for the aim of achieving tumor targeting delivery of lycorine (LYC) . The low lipophilicity of LYC made it hard to be dispersed into lipid nano-emulsions (LNEs). In order to increase its lipophilicity, lycorine-oleic acid ionic complex (LYC-OA) was made. M-LYC-OA-LNEs and uncoated lycorine-oleic acid loaded lipid nano-emulsions (LYC-OA-LNEs) were prepared by solvent injection method and characterized by transmission electron microscopy (TEM), particle size, polydispersity index, zeta-potential and entrapment efficiency analysis. The in vitro cellular uptake and growth inhibition activity studies were performed on A549 cell lines. The entrapment efficiency of M-LYC-OA-LNEs was 82.7 ± 1.6 %. The cellular uptake study showed that coated LNEs were preferably taken up by A549 cells than uncoated LNEs. The effective test by MTT assay showed better growth inhibition activity of M-LYC-OA-LNEs on A549 cell lines when compared with LYC-OA-LNEs and blank LNEs. These results demonstrated that M-LYC-OA-LNEs could be a promising formulation for tumor targeting delivery of LYC with the potential of being applied in the diagnosis and treatment of cancer.


Timing the generation of distinct retinal cells by homeobox proteins.
The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). Furthermore, by in vivo lipofection of "sensors" in which green fluorescent protein translation is under control of the 3' untranslated region (UTR), we found that the 3' UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities.


Vegetarian Diets and the Risk of Diabetes.
Worldwide, diabetes has increased steadily and in recent years, drastically. The majority of diabetes cases are type 2 (T2DM), caused by modifiable risk factors such as diet. Vegetarian diets have been studied over the past few decades for their preventative and therapeutic effects on diabetes and may be more beneficial than medication for diabetes management. A vegetarian diet characterized by whole plant foods is most beneficial for diabetes prevention and management. Vegetarian diets are inversely associated with risk of developing diabetes independent of the positive association of meat consumption with diabetes development. Vegetarian diets range from vegan (no animal products), lacto-ovo-vegetarian (no animal meat, but consumes milk and eggs), pesco-vegetarian (consumes fish), and semi-vegetarian (occasional meat consumption). There has been an observed difference in the extent of preventative and therapeutic effects of these different types of diets. The most important aspect of any of these types of diets is emphasizing whole grains, fruits and vegetables, legumes, and nuts and reducing saturated and trans fats.


Genomic analysis of Staphylococcus capitis isolated from blood cultures in neonates at a neonatal intensive care unit in Sweden.
Emergence of a genetically distinct, multidrug-resistant Staphylococcus capitis clone (NRCS-A) present in neonatal intensive care units has recently been extensively reported. The aims of the present study were to investigate which clones of S. capitis isolated from blood in a Swedish neonatal intensive care unit (NICU) have been present since 1987 and to investigate whether the NRCS-A clone has disseminated in Sweden. All S. capitis isolates from blood cultures of neonates (≤ 28 days of age) between 1987 and 2017 (n = 46) were whole-genome sequenced, and core genome multilocus sequence typing (cgMLST) was performed. Single-nucleotide polymorphism (SNP)-based phylogenetic relationships between the S. capitis isolates and in silico predictions of presence of genetic traits specific to the NRCS-A clone were identified. Furthermore, antibiotic susceptibility testing, including screening for heterogeneous glycopeptide-intermediate resistance, was performed. Thirty-five isolates clustered closely to the isolates previously determined as belonging to the NRCS-A clone and had fewer than 81 core genome loci differences out of 1063. Twenty-one of these isolates were multidrug resistant. The NRCS-A clone was found in 2001. Six pairs of isolates had differences of fewer than two SNPs. Genetic traits associated with the NRCS-A clone such as nsr, ebh, tarJ, and CRISPR were found in all 35 isolates. The increasing incidence of S. capitis blood cultures of neonates is predominantly represented by the NRSC-A clone at our NICU in Sweden. Furthermore, there were indications of transmission between cases; adherence to basic hygiene procedures and surveillance measures are thus warranted.


Maintenance of chloroplast-derived sequences in the mitochondrial DNA of Gramineae.
Evidence for the transfer of DNA from the chloroplast to the mitochondrion has been reported in many higher plants and, in most cases, the transferred chloroplast genes do not have the ability to encode functional products as a consequence of base substitutions and/or multiple rearrangements. We reported previously that the sequence of one end of a chloroplast-derived (ct-derived) fragment of DNA that contained the rps19 and trnH genes has been maintained in most gramineous plants and that its presence seems to be correlated with gene expression in this region. In the present study, we have investigated whether or not the ct-derived sequences in mitochondrial DNA (mtDNA) from some gramineous plants and species of Oryza are conserved, and whether or not such conservation is related to gene expression in these regions. We identified two junctions between ct-derived and mitochondrial sequences that were conserved among some gramineous plants. Around these regions, we found a ct-derived gene for tRNA and the promoter of a mitochondrial gene on the ct-derived sequences, respectively, and these regions were transcribed through the junctions. This result indicates that the junctions and/or regions that are transcribed and functional in mitochondria have been strongly conserved and maintained during their evolution. In Oryza, some junctions between ct-derived and mitochondrial sequences were conserved and other junctions were not. These variations seem to have been caused by deletions and/or rearrangements, and appear to be specific to the type of genome. In the case of Oryza, the timing of deletions and/or rearrangements of ct-derived sequences is likely to have coincided with the divergence of the various genome types.


Chemical composition and nutritional and medicinal value of fruit bodies and submerged cultured mycelia of culinary-medicinal higher Basidiomycetes mushrooms.
This research gives the results of a proximate analysis (moisture, ash, crude protein, fat, total carbohydrates, and total energy); a bioactive compounds analysis (γ-aminobutyric acid [GABA], ergothioneine, lovastatin, and cordycepin); fatty acid and amino acid analysis; and an analysis of macro- and microelement content of fruit bodies and mycelia of 15 higher Basidiomycetes medicinal mushroom strains belonging to 12 species. The results obtained demonstrate that almost all investigated mushrooms were found to be good sources of proteins and carbohydrates, with content varying in the ranges of 8.6-42.5% and 42.9-83.6%, respectively. Different species exhibited distinct free amino acid profiles. The total amino acid content was highest in Ophiocordyceps sinensis (MB) (23.84 mg/g) and Cordyceps militaris (FB) (23.69 mg/g). The quantification of the identified fatty acids indicated that, in general, palmitic acid, oleic acid, stearic acid, and linoleic acid were the major fatty acids. The micro- and macroelement compositions were studied, and the highest results were (as milligrams per kilogram) 224-7307 for calcium, 1668-38564 for potassium, 1091-11676 for phosphorus, and 5-97 for zinc. Bioactive components were lovastatin, GABA, and ergothioneine, which are commonly found in most mushrooms. C. militaris (FB), Pleurotus ostreatus (FB), and Coprinus comatus (FB) were most abundant and contained a high amount of GABA (756.30 μg/g, 1304.99 μg/g, 1092.45 μg/g, respectively) and ergothioneine (409.88 μg/g, 2443.53 μg/g, 764.35 μg/g, respectively). The highest lovastatin content was observed in Hericium erinaceus (FB) (14.38 μg/g) and Ganoderma lucidum (FB) (11.54 μg/g). In contrast to C. militaris (FB), cordycepin was not detected in O. sinensis (MB). The fruit body biomass of C. militaris cordycepin content reached 1.743 mg/g dry weight. The nutritional values of the mushroom species studied here could potentially be used in well-balanced diets and as sources of bioactive compounds.


Clinico- pathological profile and course of malignant pleural effusion in a tertiary care teaching hospital in western U.P. with special reference to lung cancer.
Malignant pleural effusion is a major clinical problem associated with primary and metastatic pleural malignancies. Pleural effusions from an unknown primary are responsible for 7-15% of all malignant pleural effusions. Presence of malignant pleural effusion puts the patient in advanced stage and renders the prognosis as poor. In this study we intend to find out the incidence of malignant pleural effusion, its aetiology and clinical course in patients attending a tertiary care teaching hospital. A total of 308 patients were included in this study. A majority of the patients were in age group 50- 70 years (median age = 58.8 years; range 32- 85 yrs). Male to female ratio was 2.5:1. The major primary cancers were lung cancer (135), lymphoma (40), breast cancer (36), female genital tract (30) gastrointestinal (21), and others (8). In 38 cases primary remained unknown. The yields of pleural fluid cytology, blind pleural biopsy, CT/USG guided pleural biopsy and thoracoscopy were 60%, 49%, 76% and 91% respectively. Chemical pleurodesis yielded complete response in 80%, incomplete response in another 13% patients. Only 136 (44%) cases could be followed up for minimum of 6 months. A majority of them (95, 69.85%) died. We conclude that malignant pleural effusion is a commonly misdiagnosed medical entity. Lung cancer is the commonest cause. Despite all efforts, in about 15% of the cases, primary remains undiagnosed. Thoracoscopy/pleuroscopy is a cost effective measure for diagnosis. Chemical pleurodesis provides expected results but mortality remains high.


Industrial Hog Operation Workers' Perspectives on Occupational Exposure to Zoonotic Pathogens: A Qualitative Pilot Study in North Carolina, USA.
Industrial hog operation (IHO) workers face a range of occupational hazards, including exposure to zoonotic pathogens such as livestock-associated antimicrobial-resistant Staphylococcus aureus and swine-origin influenza viruses with epidemic or pandemic potential. To better understand this population's occupational exposure to zoonotic pathogens, we conducted a community-driven qualitative research study in eastern North Carolina. We completed in-depth interviews with ten IHO workers and used thematic analysis to identify and analyze patterns of responses. Workers described direct and indirect occupational contact with hogs, with accompanying potential for dermal, ingestion, and inhalation exposures to zoonotic pathogens. Workers also described potential take-home pathways, wherein they could transfer livestock-associated pathogens and other contaminants from IHOs to their families and communities. Findings warrant future research, and suggest that more restrictive policies on antimicrobials, stronger health and safety regulations, and better policies and practices across all IHOs could afford greater protection against worker and take-home zoonotic pathogen exposures.


Roscovitine, a novel cyclin-dependent kinase inhibitor, characterizes restriction point and G2/M transition in tobacco BY-2 cell suspension.
Although the developmental programs of plants and animals differ, key regulatory components of their cell cycle have been conserved. Particular attention has been paid to the role of the complexes between highly conserved cyclin and cyclin-dependent kinases in regulating progression through the cell cycle. The recent demonstration that roscovitine is a potent and selective inhibitor of the animal cyclin-dependent kinases cdc2 (CDK1), CDK2 and CDK5 prompted an investigation into its effects on progression through the plant cell cycle. Roscovitine induced arrests both in late G1 and late G2 phase in BY-2 tobacco cell suspensions. Both block were fully reversible when roscovitine was used at concentrations similar to those used in the animal system. Stationary-phase cells subcultured in the presence of roscovitine were arrested at a 2C DNA content. This arrest was more efficient without exogenous addition of plant growth regulator. Roscovitine induced a block in G1 earlier than that induced by aphidicolin. S-phase synchronized cells treated with roscovitine were arrested at a 4C DNA content at the G2/ M transition. The expression analysis of a mitotic cyclin (NTCYC1) indicated that the roscovitine-induced G2 block probably occurs in late G2. Finally, cells in metaphase were insensitive to roscovitine. The purified CDK/cyclin kinase activities of late G1 and early M arrested cells were inhibited in vitro by roscovitine. The implications of these experimental observations for the requirement for CDK activity during progression through the plant cell cycle are discussed.


Structural organization of the Corynebacterium glutamicum plasmid pCG100.
pCG100, a 3 kb cryptic plasmid of Corynebacterium glutamicum ATCC 13058, probably identical with pSR1 from C. glutamicum ATCC 19223, was characterized. The minimum region for autonomous replication was shown to be contained on a 1.9 kb BglII-NcoI fragment; a 380 bp HindIII-SphI fragment can replicate in the presence of the parental plasmid, which presumably provides a trans-acting replication factor. Derivatives of pCG100 are able to replicate in several Corynebacterium, Brevibacterium and Arthrobacter strains. pCG100 is compatible with pBL1, a cryptic plasmid of Brevibacterium lactofermentum. Shuttle plasmid vectors, containing the kanamycin-resistance gene from Tn903 or from Streptococcus faecalis as selectable markers and the AmpR, TetR or lacZ alpha genes for insertional inactivation, were constructed using the minimum replication fragment of pCG100.