Clinical Characteristics and Risk Factors of Recurrent Mooren's Ulcer.
To investigate the clinical characteristics of Mooren's ulcer in East China and to identify the potential risk factors that affect the recurrence of Mooren's ulcer. We reviewed the medical records of 95 patients (100 eyes) diagnosed with Mooren's ulcer from May 2005 to December 2014. The patients were classified into recurrent and nonrecurrent groups and followed up for 18 months. The difference between two groups was estimated. The patients in the recurrent group were subdivided according to the history of corneal infection and corneal perforation, respectively. The recurrent time in the subgroups was analyzed. Patients in the recurrent group were more likely to have a history of corneal infection and corneal perforation than that in the nonrecurrent groups. In patients with recurrent Mooren's ulcer, the median time to first recurrence was 130 days in the infection group, 480 days in noninfection group, and 195 days in the perforation group versus 480 days in nonperforation group. Corneal infection and corneal perforation were associated with early recurrence of Mooren's ulcer. The tailored follow-up schedule should be used for patients with corneal infection and corneal perforation due to the high risk of recurrence.


Exoskeleton may influence the internal body temperatures of Neotropical dung beetles (Col. Scarabaeinae).
The insect exoskeleton is a multifunctional coat with a continuum of mechanical and structural properties constituting the barrier between electromagnetic waves and the internal body parts. This paper examines the ability of beetle exoskeleton to regulate internal body temperature considering its thermal permeability or isolation to simulated solar irradiance and infrared radiation. Seven Neotropical species of dung beetles (Coleoptera, Scarabaeinae) differing in colour, surface sculptures, size, sexual dimorphism, period of activity, guild category and altitudinal distribution were studied. Specimens were repeatedly subjected to heating trials under simulated solar irradiance and infrared radiation using a halogen neodymium bulb light with a balanced daylight spectrum and a ceramic infrared heat emitter. The volume of exoskeleton and its weight per volume unit were significantly more important for the heating rate at the beginning of the heating process than for the asymptotic maximum temperature reached at the end of the trials: larger beetles with relatively thicker exoskeletons heated more slowly. The source of radiation greatly influences the asymptotic temperature reached, but has a negligible effect in determining the rate of heat gain by beetles: they reached higher temperatures under artificial sunlight than under infrared radiation. Interspecific differences were negligible in the heating rate but had a large magnitude effect on the asymptotic temperature, only detectable under simulated sun irradiance. The fact that sun irradiance is differentially absorbed dorsally and transformed into heat among species opens the possibility that differences in dorsal exoskeleton would facilitate the heat gain under restrictive environmental temperatures below the preferred ones. The findings provided by this study support the important role played by the exoskeleton in the heating process of beetles, a cuticle able to act passively in the thermal control of body temperature without implying energetic costs and metabolic changes.


Calcium supplementation decreases BCP-induced inflammatory processes in blood cells through the NLRP3 inflammasome down-regulation.
Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP results from its down-modulating effect on P2X7R gene expression and its capacity to inhibit ATP/P2X7R interactions, decreasing the NLRP3 inflammasome activation. Considering that monocytes have a vast regenerative potential, and since the excessive inflammation often observed after bone substitutes implantation limits their performance, our results might have great implications in terms of understanding the mechanisms leading to an efficient bone reconstruction. Although scaffolds and biomaterials unavoidably come into direct contact with blood during bone defect filling, whole blood-biomaterials interactions have been poorly explored. By studying in 3D the interactions between biphasic calcium phosphate (BCP) in microparticulate form and blood, we showed for the first time that calcium supplementation of BCP microparticles (BCP/Ca) has anti-inflammatory properties compared to BCP-induced inflammation in whole blood cells and provided information related to the molecular mechanisms involved. The present study also showed that BCP, as well as BCP/Ca particles stimulate monocyte proliferation. As monocytes represent a powerful target for regenerative therapies and as an excessive inflammation limits the performance of biomaterials in bone tissue engineering, our results might have great implications to improve bone reconstruction.


5 ways to minimize duplicate patient records.
Realizing that data integrity and patient information accuracy are crucial to proper payment, Texas Health Resources reduced its duplicate patient records by 21 percent to achieve cleaner claims and faster cash flow. Here are five ways the 13-hospital system met this challenge.


[Endocrine ophthalmology. An overview of pathology, classification, and therapy].
A new uniform nomenclature will allow more accurate clinical study of endocrine ophthalmopathy, a disease that remains an enigma. Clinical eye disease develops in 30-60% of patients with Graves' disease, but the severe malignant form occurs in a maximum of 5%, and most of these latter patients have been rendered euthyroid or hypothyroid by treatment of the hyperthyroidism. Despite claims to the contrary, there is no convincing evidence that the mode of treatment (antithyroid drugs, surgery or radioiodine) has a bearing on the development of ophthalmopathy. Circulating fragments of the TSH-molecule, which produce swelling of retroorbital tissue, and as autoimmune processes of the delayed type are currently under consideration as causative factors. Medical treatment of endocrine ophthalmopathy has only a limited effect. In cases of rapid progression with deterioration of vision it is recommended that operative decompression, preferably into the maxillary and ethmoidal sinus, be performed without delay. Retroorbital administration of 2000 rad by a highly collimated megavoltage beam appears to be a valuable alternative to surgery.


Kinetics of fluoride removal from plasma and bone of rats after chronic intake of fluoride.
This study evaluated the kinetics of fluoride in plasma, femur surface and the whole femur of rats, after chronic exposure to different water fluoride levels was interrupted. Four groups of Wistar rats received drinking water containing 0, 5, 15 or 50 microg F/ml for 60 days (n = 50/group). The animals were euthanized immediately after exposure to fluoride or after 7, 30, 90 or 180 days (n = 10/subgroup). Plasma and femurs were collected. Fluoride on the femur surface, whole femur and plasma was analyzed with an electrode. Data were analyzed using ANOVA and Tukey's test (p< 0.05). The increase in plasma fluoride levels was significant only for the 50 microg F/ml group at 0 and 7 days. Regarding bone surface and whole bone, for most groups, significant increases in fluoride concentrations were observed with the increase in water fluoride concentrations at each time of euthanasia. For fluoride doses up to 15 microg F/ml, femur surface fluoride levels were reestablished 180 days after the exposure was discontinued, which was not valid for whole femur or for higher fluoride doses. We found a different kinetics of fluoride in plasma, femur surface and the whole femur of rats after chronic exposure to fluoride is interrupted.


Attenuation by Time-Restricted Feeding of High-Fat and High-Fructose Diet-Induced NASH in Mice Is Related to Per2 and Ferroptosis.
Nonalcoholic steatohepatitis (NASH) is a chronic and progressive disease whose treatment strategies are limited. Although time-restricted feeding (TRF) is beneficial for metabolic diseases without influencing caloric intake, the underlying mechanisms of TRF action in NASH and its efficacy have not yet been demonstrated. We herein showed that TRF effectively alleviated NASH, producing a reduction in liver enzymes and improvements in liver pathology. Regarding the mechanisms by which TRF mitigates NASH, we ascertained that TRF inhibited ferroptosis and the expression of the circadian gene Per2. By adopting a hepatocyte-specific Per2-knockout (Per2△hep) mice model, we clarified the critical role of Per2 in exacerbating NASH. According to the results of our RNA-Seq analysis, the knockout of Per2 ameliorated NASH by inhibiting the onset of ferroptosis; this was manifested by diminished lipid peroxidation levels, decreased mRNA and protein levels for ferroptosis-related genes, and alleviated morphologic changes in mitochondria. Furthermore, using a ferroptosis inhibitor, we showed that ferroptosis significantly aggravated NASH and noted that this was likely achieved by regulation of the expression of peroxisome proliferator activated receptor (PPAR)α. Finally, we discerned that TRF and hepatocyte-specific knockout of Per2 promoted the expression of PPARα. Our results revealed a potential for TRF to effectively alleviate high-fat and high-fructose diet-induced NASH via the inhibition of Per2 and depicted the participation of Per2 in the progression of NASH by promoting ferroptosis, which was ultimately related to the expression of PPARα.


Comparison of fluorescent consensus IgH PCR and allele-specific oligonucleotide probing in the detection of minimal residual disease in childhood ALL.
The sensitivity of detection of residual disease by two IgH PCR strategies, fluorescent framework 3 (Ffr3) and allele-specific oligonucleotide probing (ASOP), was compared in 57 'remission' BM samples obtained from 19 children with B-lineage acute lymphoblastic leukaemia (ALL). Oligonucleotide probing was more sensitive than FFr3 PCR in 10/16 cases, achieving a sensitivity of 0.01% or greater in 15/16 cases. Comparable sensitivities were obtained in the six remaining cases; the FFr3 PCR achieving a sensitivity of 0.1% or greater in 14/16 cases. 39/57 'remission' BM samples analysed showed no evidence of MRD by either technique although 18 were positive by ASOP and 14 positive by FFr3 PCR. The level of disease was estimated to be 0.01% or less in the four false negative samples.


[Static Migration and Release of Dibutyl-Phthalate in the Fluctuating Zone of Three Gorges Reservoir].
Phthalic acid esters (PAEs) have received increasing attention in recent years due to their widespread use and hazards to human health and fertility in the environment. In order to understand the migration and release processes of organic pollutants in huge fluctuating zone soil, Dibutyl-phthalate(DBP) was chosen as a typical substance, and its migration and release characteristics in the fluctuating zone of the Three Gorges Reservoir to overlying water and the impacts of DBP concentration in the soil, ionic strength and the concentration of organic mater in overlying water on the process were studied using static flooding method. The results showed that DBP migrated from the soil to the overlying water in the early days after flooding, and the release process of DBP was divided into two phases: one was quick release with a relatively short releasing time and a rapid releasing rate; the other was slow release with a relatively long releasing time and a slow releasing rate. The migration and release processes were well fitted by two-compartment first-order kinetics. After different concentrations DBP were added into soil, the rate of quick release increased with the increasing DBP concentrations in soil while the percent of quick release decreased with the increasing DBP concentrations. The results of rate of slow release and the percent of slow release were on the contrary. The water conditions of overlying water could impact the migration and releasing process of DBP when the soil in fluctuating zone was flooded. The amount of DBP released into the overlying water would increase when the ionic strength in the water increased. At the same time, when the ionic strength increased, in spite of the decreasing quick release rate, the percent of quick release increased. The higher concentration of organic matter in overlying water, the more the amount of DBP released into the overlying water. At the same time, all of the rates of quick release, slow release and the percent of quick release would increase with the increasing concentrations of organic matter, while there was almost no influence on the percent of slow release of DBP.


[Efficiency of interlamellar refractive tunnel keratoplasty in myopia and astigmatism correction].
Correction of high degree myopia, anisometropia and astigmatism continues to remain one of actual problems of ophthalmology. The purpose of the present work - the analysis of results of application of refractive interlamellar tunnel keratoplasty variants. We develop 6 updatings tunnel keratoplasty. In total in clinic 310 operations from which in 158 cases as a transfer material used a donor cornea, in 63 cases - brephocornea (a fruit cornea) and in 89 cases - hydrogel synthetic implant, modified in low-temperature to gas-discharge plasma are spent. From the specified number of operative interventions, on 86 eyes of operation tunnel keratoplasty have been spent at those patients by whom earlier it has been given up in carrying out eximerlaser corrections, in connection with presence of a "thin", "flat" and "convex" cornea. Maximum refractive effect fell first two weeks after operation. Definitive stabilisation of a refraction occurred on 2-3 month, thus regress of the reached effect made an order of 10-12 %. It is reached refractive effect from 5,5 to 20,0 D. Undercorrection in some cases made to 3,5 D, that spoke very high myopia (more than 20,0 D) degrees. It has been noticed, that refractive effect of operations with ecsplants was above (on the average on 10 %), than at use of a donor cornea, at identical cross-section section of used transfer materials. It spoke that the synthetic material, unlike a donor cornea, kept the form. At all patients substantial increase of visual acuities has been received, and in 75 % it was equal or exceeded visual acuity before operation with the greatest possible correction. Thus, clinical approbation has proved, that the variants of tunnel keratoplasty, are effective ways of high myopia, anisometropia and astigmatism correction. Updating in gaseous plasma is represented in the perspective way of improvement of biocompatibility of synthetic materials.


Interleukin 6 receptor (IL-6R) was an independent prognostic factor in cervical cancer.
IL-6 has been found to be associated with poor response to chemoradiotherapy and poor overall prognosis of patients with cervical cancer. However, little is known about the clinicopathological significance of IL-6 receptor (IL-6R) expression in the setting of cervical cancer. To investigate the clinicopathological meaning of IL-6R in cervical cancer, expression of IL-6R was detected using immunohistochemistry in cervical cancer tissue microarray composed of 98 cases of cervical cancer and paired normal controls. As further confirmation of expression trend, western-blotting was conducted in another independent 36 pairs of cervical cancer and matched normal controls. Subsequently, the statistical correlation between IL-6R expression and clinicopathological variables was analyzed, including demographic, TNM stage, clinical grading and overall prognosis. IL-6R expression was shown to be remarkably associated with lymph node metastasis, recurrence and overall prognosis. Moreover, only IL-6R expression was observed to be an independent prognostic factor among these variables that could potentially influence the overall prognosis of patients with cervical cancer. In conclusion, IL-6R was shown to be an independent prognostic factor for patients with cervical cancer.


Self-assembly of discrete metal complexes in aqueous solution via block copolypeptide amphiphiles.
The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal-metal interactions and supramolecular assembly. Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self-assembly into structures such as nanoparticles, nanosheets and nanofibers. In this study, we combined these two concepts by investigating the self-assembly of discrete metal complexes in aqueous solution using block copolypeptides. Normally, discrete metal complexes such as [Au(CN)(2)]-, when molecularly dispersed in water, cannot interact with one another. Our results demonstrated, however, that the addition of block copolypeptide amphiphiles such as K(183)L(19) to [Au(CN)(2)]- solutions induced one-dimensional integration of the discrete metal complex, resulting in photoluminescence originating from multinuclear complexes with metal-metal interactions. Transmission electron microscopy (TEM) showed a fibrous nanostructure with lengths and widths of approximately 100 and 20 nm, respectively, which grew to form advanced nanoarchitectures, including those resembling the weave patterns of Waraji (traditional Japanese straw sandals). This concept of combining block copolypeptide amphiphiles with discrete coordination compounds allows the design of flexible and functional supramolecular coordination systems in water.


Lung cancer screening using low-dose CT and FDG-PET in liver transplant recipients.
To address the feasibility of implementing a lung cancer screening program in liver transplant recipients (LTR) targeted to detect early-stage lung cancer one hundred twenty-four LTR (89% male, 59.8+/-8.8 y old), who entered the lung cancer screening program at our hospital were reviewed. The results of the diagnostic algorithm using low-dose CT and F-18-fluorodeoxyglycose positron emission tomography (FDG-PET) were analyzed. Lung cancer was detected in 12 LTR (9.7%), most of which corresponded to the non-small cell subtype. Two of the 12 lung cancers were detected in the baseline study (prevalence of 1.6%), whereas 10 patients were diagnosed with lung cancer in the follow-up (incidence of 8.1%). Considering all cancers, 10 of 12 (83.3%) were diagnosed at stage I, one cancer was diagnosed at stage IIIA, and another one at stage IV. The sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of F-18-fluorodeoxyglycose positron emission tomography to detect malignancy in our cohort were 81.8%,100%, 99.3%, 100%, and 99.3%, respectively. A carefully followed multidisciplinary lung cancer screening algorithm in LTR that includes F-18-fluorodeoxyglycose positron emission tomography and low-dose CT allows lung cancer to be diagnosed at an early stage while reducing unnecessary invasive procedures.


Complexes of potentially pathogenic microscopic fungi in anthropogenic polluted soils.
This study was undertaken to investigate the species' diversity and structure of potentially pathogenic microscopic fungal complexes in podzolic soils polluted by fluorine, heavy metals (Cu, Ni, Co), oil products (diesel fuel, gas condensate, mazut). Lists of potentially pathogenic fungi isolated from soils are made specifically for north-western part of Russia (Kola Peninsula). The majority of studied fungus species belong to the following genera: Penicillium, Aspergillus, Mucor, Lecanicillium and Phoma. Penicillium miczynskii was identified as the most stable type of fungus with respect to all studied types of oil products. Mucor hiemalis was identified as the most sensitive type. An increase of 15% portion of potentially pathogenic fungi as compared to the background soil in zones of aluminum and copper-nickel plants was revealed. The results indicate an increase of 20-25% of potentially pathogenic fungi in pollution of soil with oil products. The structure of fungal complexes was observed to have changed in the polluted soils and the species number and frequency of occurrence of potentially pathogenic fungi were also increased.


Impact of intensive newborn care on neonatal mortality in a community hospital.
Development of a Perinatal Center delivering Level 3 intensive care in a community hospital is described. The inborn neonatal mortality at the hospital in which the Center is located, as well as that of the 13 surrounding counties, has diminished more rapidly than the state neonatal mortality. This has coincided with an almost constant delivery rate, increased proportion of staff patients, relatively constant rate of low birth weight, and declining total perinatal mortality. Our experience suggests that appropriately trained and motivated people, not equipment or geographic location, represent the key factor in the development of such a center.


Secretion of interleukin-6 by peripheral blood mononuclear cells from patients with pulmonary tuberculosis and their contacts.
The acute phase response, cell-mediated immunity and delayed type hypersensitivity in pulmonary tuberculosis (TB) may be mediated and regulated by the synthesis and release of interleukins 1 and 6 (IL-1, IL-6) and tumour necrosis factor (TNF) alpha. To examine this, peripheral blood mononuclear cells (PBMC) from TB patients, healthy controls and socially matched controls were cultured in the presence or absence of 5 micrograms/ml lipopolysaccharide-endotoxin (LPS) for 48 hours. IL-6 in the supernatant fluids (SNF) was measured using biological and immunoassays. Spontaneous release of functionally active IL-6 was significantly increased in PBMC SNF of TB patients when compared with both healthy controls and socially matched controls (median values of 4265, 356 and 1245 pg/10(6) cells respectively, p < 0.001). PBMC of social controls produced markedly more IL-6 than those of healthy controls (p < 0.001). LPS stimulated IL-6 production showed similar patterns for TB patients, healthy and social controls (median values of 6806, 1291 and 2667 pg/10(6) cells respectively, p < 0.001). In all three groups, LPS-stimulated cells produced significantly more IL-6 than non-stimulated cultures (p < 0.001). Constitutive production of IL-6 by PBMC from TB patients implies pre-activation of cells and suggests that IL-6 may be important in the regulation of the acute phase response in TB. Discrepant IL-6 release between the two control groups may be secondary to subclinical mycobacterial infection with non-specific immunological activation in the social controls.


Induction of stress response and differential expression of 70 kDa stress proteins by sodium fluoride in HeLa and rat brain tumor 9L cells.
We herein demonstrate that sodium fluoride (NaF) acts as a stress response inducer on HeLa and 9L rat brain tumor cells. NaF is only slightly cytotoxic, and inhibitory to Ser/Thr-phosphatases but not to Tyr-phosphatases in both cell lines. After treatment with 5 mM NaF for 2 h, the phosphorylation levels of vimentin and an alkali-resistant 65-kDa phosphoprotein were enhanced, a common phenomenon detected in cells under a variety of stress conditions. Under an identical treatment protocol, in which the cells were treated with 5 mM NaF for 2 h and then allowed to recover under normal growing conditions for up to 12 h, NaF differentially induced the cytoplasmic/nuclear heat-shock protein70s (including both the inducible and the constitutively expressed members of this protein family) in HeLa cells and the endoplasmic reticulum residing heat-shock protein70 (the glucose-regulated protein with an apparent molecular weight of 78 kDa) in 9L cells. Electrophoretic mobility shift assays (EMSA) using probes containing well-characterized regulatory elements revealed the activation of the heat-shock factor in HeLa but not in 9L cells; this is in good agreement with the stress protein induction pattern. Additional differential induction of binding activities toward EMSA probes individually containing NF-KB, AP-2, and CRE-like elements were detected in NaF-treated cells. The possible involvement of these binding sites as well as the corresponding factors in the stress response are discussed.


The global transcriptional regulators, SSN6 and TUP1, play distinct roles in the establishment of a repressive chromatin structure.
Repression of a-cell specific gene expression in yeast alpha cells requires MAT alpha 2 and MCM1, as well as two global repressors, SSN6 and TUP1. Previous studies demonstrated that nucleosomes positioned adjacent to the alpha 2/MCM1 operator in alpha cells directly contribute to repression. To investigate the possibility that SSN6 and TUP1 provide a link between MAT alpha 2/MCM1 and neighboring histones, nucleosome locations were examined in ssn6 and tup1 alpha cells. In both cases, nucleosome positions downstream of the operator were disrupted, and the severity of the disruption correlated with the degree of derepression. Nevertheless, the observed changes in chromatin structure were not dependent on transcription. Our data strongly indicate that SSN6 and TUP1 directly organize repressive regions of chromatin.


Reflection on modern methods: Dynamic prediction using joint models of longitudinal and time-to-event data.
Individualized prediction is a hallmark of clinical medicine and decision making. However, most existing prediction models rely on biomarkers and clinical outcomes available at a single time. This is in contrast to how health states progress and how physicians deliver care, which relies on progressively updating a prognosis based on available information. With the use of joint models of longitudinal and survival data, it is possible to dynamically adjust individual predictions regarding patient prognosis. This article aims to introduce the reader to the development of dynamic risk predictions and to provide the necessary resources to support their implementation and assessment, such as adaptable R code, and the theory behind the methodology. Furthermore, measures to assess the predictive performance of the derived predictions and extensions that could improve the predictions are presented. We illustrate personalized predictions using an online dataset consisting of patients with chronic liver disease (primary biliary cirrhosis).


Phase transitions of a polymer threading a membrane coupled to coil-globule transitions.
We theoretically study phase transitions of a polymer threading through a pore imbedded in a membrane. We focus on the coupling between a partition of the polymer segments through the membrane and a coil-globule transition of the single polymer chain. Based on the Flory model for collapse transitions of a polymer chain, we calculate the fraction of polymer segments and the expansion factor of a polymer coil on each side of the membrane. We predict a first-order phase transition of a polymer threading a membrane; polymer segments in one side are discontinuously translocated into the other side, depending on solvent conditions and molecular weight of the polymer. We also discuss the equilibrium conformation of the polymer chain on each side of the membrane.


[Semisynthetic cellulose derivatives as the base of hydrophilic gel systems].
The field of drug technology widely ulilizes gel systems of high-molecular substances, which have a number of advantages, such as low toxicity, availability, unique physical properties, biocompatibility, mucoadhesivity, and others. Gel systems are used in the field of local as well as general therapy, in both shape-specific and shape-non-specific dosage forms, in medicaments of the first, second, and third generations. An important group of gels employed in pharmacy are hydrophilic gels or hydrogels, most frequently composed of hydrophilic polymers of natural, semisynthetic and synthetic origin. Though cellulose derivatives as the representatives of polymers of semisynthetic origin are used in pharmaceutical technology for a long time, their research continues and their other possible uses are being searched for. Their advantages include especially safety, easy availability, and a relatively low price. The review paper describes selected cellulose derivatives, their properties and uses in pharmaceutical technology with regard to their use in the field of production of gel systems.


Separating in vivo mechanical stimuli for postpneumonectomy compensation: imaging and ultrastructural assessment.
Following right pneumonectomy (PNX), the remaining lung expands and its perfusion more than doubles. Tissue and microvascular mechanical stresses are putative stimuli for compensatory lung growth and remodeling, but their relative contribution remains uncertain. To temporally separate expansion- and perfusion-related stimuli, we replaced the right lung of adult dogs with a customized inflated prosthesis. Four months later, the prosthesis was either acutely deflated (DEF) or kept inflated (INF). Thoracic high-resolution computed tomography (HRCT) was performed pre- and post-PNX before and after prosthesis deflation. Lungs were fixed for morphometric analysis ∼12 mo post-PNX. The INF prosthesis prevented mediastinal shift and lateral lung expansion while allowing the remaining lung to expand 27-38% via caudal elongation, associated with reversible capillary congestion in dependent regions at low inflation and 40-60% increases in the volumes of alveolar sepal cells, matrix, and fibers. Delayed prosthesis deflation led to further significant increases in lung volume, alveolar tissue volumes, and alveolar-capillary surface areas. At postmortem, alveolar tissue volumes were 33% higher in the DEF than the INF group. Lateral expansion explains ∼65% of the total post-PNX increase in left lung volume assessed in vivo or ex vivo, ∼36% of the increase in HRCT-derived (tissue + microvascular blood) volume, ∼45% of the increase in ex vivo septal extravascular tissue volume, and 60% of the increase in gas exchange surface areas. This partition agrees with independent physiological measurements obtained in these animals. We conclude that in vivo signals related to lung expansion and perfusion contribute separately and nearly equally to post-PNX growth and remodeling.


Virtue Ethics in Monetized Medicine.
This review essay situates Abraham Nussbaum's The Finest Traditions of Our Calling (2016) within the contemporary genre of physician memoirs that shade into critiques of institutional medicine. Nussbaum's primary concern is the demoralization of medicine as it becomes increasingly monetized; patients are reduced to body parts and reimbursement schedules. He argues that physicians continue to have considerable choice in how they practice, despite institutional constraints. For bioethics, Nussbaum's advocacy of virtue ethics is notable. His book is a moving testimonial to contemporary problems, but also a manifesto for possibilities of change at the individual level.


Acetylcholine reduces palmitate-induced cardiomyocyte apoptosis by promoting lipid droplet lipolysis and perilipin 5-mediated lipid droplet-mitochondria interaction.
Lipid droplets (LDs), which are neutral lipid storage organelles, are important for lipid metabolism and energy homeostasis. LD lipolysis and interactions with mitochondria are tightly coupled to cellular metabolism and may be potential targets to buffer the effects of excessive toxic lipid species levels. Acetylcholine (ACh), the major neurotransmitter of the vagus nerve, exhibits cardioprotective effects. However, limited research has focused on its effects on LD lipolysis and the LD-mitochondria association in fatty acid (FA) overload models. Here, we reveal that palmitate (PA) induces an increase in expression of the FA transport protein cluster of differentiation 36 (CD36) and LD formation; remarkably reduces the expression of lipases involved in triacylglycerol (TAG) lipolysis, such as adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL); impairs LD-mitochondria interaction; and decreases perilipin 5 (PLIN5) expression, resulting in LD accumulation and mitochondrial dysfunction, which ultimately lead to cardiomyocyte apoptosis. ACh significantly upregulates PLIN5 expression and improved LD lipolysis and the LD-mitochondria association. Moreover, ACh reduces CD36 expression, LD deposition and mitochondrial dysfunction, ultimately suppressing apoptosis in PA-treated neonatal rat ventricular cardiomyocytes (NRVCs). Knockdown of PLIN5, which plays a role in LD-mitochondria contact site formation, abolishes the protective effects of ACh in PA-treated NRVCs. Thus, ACh protects cardiomyocytes from PA-induced apoptosis, at least partly, by promoting LD lipolysis and activating LD-mitochondria interactions via PLIN5. These findings may aid in developing novel therapeutic approaches that target LD lipolysis and PLIN5-mediated LD-mitochondria interactions to prevent or alleviate lipotoxic cardiomyopathy.


Optimal measurement on noisy quantum systems.
We identify the optimal measurement for obtaining information about the original quantum state after the state to be measured has undergone partial decoherence due to noise. We quantify the information that can be obtained by the measurement in terms of the Fisher information and find its value for the optimal measurement. We apply our results to a quantum control scheme based on a spin-boson model.


New steroidal glycosides from rhizomes of Clintonia udensis.
A total of 10 steroidal glycosides, together with three new spirostanol glycosides (6-8), a new furostanol glycoside (9), and a new cholestane glycoside (10), were isolated from the rhizomes of Clintonia udensis (Liliaceae). The structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including 2-D nuclear magnetic resonance (NMR) data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. The isolated glycosides were evaluated for their cytotoxic activity against HL-60 leukemia cells. Spirostanol glycosides 1 and 2, and furostanol glycoside 4 showed cytotoxic activity with IC(50) values of 3.2+/-0.02, 2.2+/-0.12, and 2.2+/-0.06 microg/ml, respectively. Neither the spirostanol and furostanol saponins with a hydroxy group at C-1 (6 and 9) and C-12 (7 and 8) nor cholestane glycosides (5 and 10) exhibited apparent cytotoxic activity at a sample concentration of 10 microg/ml.


Isolation, Culturing, and Differentiation of Primary Myoblasts from Skeletal Muscle of Adult Mice.
Myogenesis is a multi-step process that leads to the formation of skeletal muscle during embryonic development and repair of injured myofibers. In this process, myoblasts are the main effector cell type which fuse with each other or to injured myofibers leading to the formation of new myofibers or regeneration of skeletal muscle in adults. Many steps of myogenesis can be recapitulated through in vitro differentiation of myoblasts into myotubes. Most laboratories use immortalized myogenic cells lines that also differentiate into myotubes. Although these cell lines have been found quite useful to delineating the regulatory mechanisms of myogenesis, they often show a great degree of variability depending on the origin of the cells and culture conditions. Primary myoblasts have been suggested as the most physiologically relevant model for studying myogenesis in vitro. However, due to their low abundance in adult skeletal muscle, isolation of primary myoblasts is technically challenging. In this article, we describe an improved protocol for the isolation of primary myoblasts from adult skeletal muscle of mice. We also describe methods for their culturing and differentiation into myotubes.


Molecular analysis of androgen resistance syndromes in Egyptian patients.
Androgen resistance syndromes [i.e. 5 alpha-reductase deficiency (5 alpha RD) and androgen receptor (AR) defects] are frequently reported among Egyptian intersex patients. This study examined AR and 5 alpha-reductase 2 (5 alpha R2) gene mutations among a sample of such cases as a first step towards instituting a screening program. Five families with a typical hormonal profile of 5 alpha RD were screened for major deletions of exons 3-5 of the 5 alpha R2 gene, using polymerase chain reaction (PCR) and electrophoresis. Thereafter, screening for point mutations was carried out by single strand conformational polymorphism (SSCP) analysis, followed by nucleotide sequencing. Seven patients with androgen insensitivity syndrome (AIS) were subjected to molecular analysis of AR exons B-H by a similar protocol, except for the use of denaturing gradient gel electrophoresis (DGGE) for screening point mutations. No major deletions were found in either gene. One family had abnormal electrophoretic mobility on SSCP of exon 5 of the 5 alpha R2 gene, resulting from a point mutation (C to T substitution) at codon 246. Another family, showing retarded mobility on DGGE, had a point mutation (G to A substitution) at codon 889 of the AR gene. In conclusion, the study revealed two mutations previously reported in other geographically distinct populations, inferring the possibility of mutational hot spots in the genes.


Reclassification of a likely pathogenic Dutch founder variant in KCNH2; implications of reduced penetrance.
Variants in KCNH2, encoding the human ether a-go-go (hERG) channel that is responsible for the rapid component of the cardiac delayed rectifier K+ current (IKr), are causal to long QT syndrome type 2 (LQTS2). We identified eight index patients with a new variant of unknown significance (VUS), KCNH2:c.2717C > T:p.(Ser906Leu). We aimed to elucidate the biophysiological effect of this variant, to enable reclassification and consequent clinical decision-making. A genotype-phenotype overview of the patients and relatives was created. The biophysiological effects were assessed independently by manual-, and automated calibrated patch clamp. HEK293a cells expressing (i) wild-type (WT) KCNH2, (ii) KCNH2-p.S906L alone (homozygous, Hm) or (iii) KCNH2-p.S906L in combination with WT (1:1) (heterozygous, Hz) were used for manual patching. Automated patch clamp measured the variants function against known benign and pathogenic variants, using Flp-In T-rex HEK293 KCNH2-variant cell lines. Incomplete penetrance of LQTS2 in KCNH2:p.(Ser906Leu) carriers was observed. In addition, some patients were heterozygous for other VUSs in CACNA1C, PKP2, RYR2 or AKAP9. The phenotype of carriers of KCNH2:p.(Ser906Leu) ranged from asymptomatic to life-threatening arrhythmic events. Manual patch clamp showed a reduced current density by 69.8 and 60.4% in KCNH2-p.S906L-Hm and KCNH2-p.S906L-Hz, respectively. The time constant of activation was significantly increased with 80.1% in KCNH2-p.S906L-Hm compared with KCNH2-WT. Assessment of KCNH2-p.S906L-Hz by calibrated automatic patch clamp assay showed a reduction in current density by 35.6%. The reduced current density in the KCNH2-p.S906L-Hz indicates a moderate loss-of-function. Combined with the reduced penetrance and variable phenotype, we conclude that KCNH2:p.(Ser906Leu) is a low penetrant likely pathogenic variant for LQTS2.


Detecting Preknowledge Cheating via Innovative Measures: A Mixture Hierarchical Model for Jointly Modeling Item Responses, Response Times, and Visual Fixation Counts.
Preknowledge cheating jeopardizes the validity of inferences based on test results. Many methods have been developed to detect preknowledge cheating by jointly analyzing item responses and response times. Gaze fixations, an essential eye-tracker measure, can be utilized to help detect aberrant testing behavior with improved accuracy beyond using product and process data types in isolation. As such, this study proposes a mixture hierarchical model that integrates item responses, response times, and visual fixation counts collected from an eye-tracker (a) to detect aberrant test takers who have different levels of preknowledge and (b) to account for nuances in behavioral patterns between normally-behaved and aberrant examinees. A Bayesian approach to estimating model parameters is carried out via an MCMC algorithm. Finally, the proposed model is applied to experimental data to illustrate how the model can be used to identify test takers having preknowledge on the test items.


Control of fed-batch fermentations.
Fed-batch fermentation is used to prevent or reduce substrate-associated growth inhibition by controlling nutrient supply. Here we review the advances in control of fed-batch fermentations. Simple exponential feeding and inferential methods are examined, as are newer methods based on fuzzy control and neural networks. Considerable interest has developed in these more advanced methods that hold promise for optimizing fed-batch techniques for complex fermentation systems.


Suppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery.
Heterotopic ossification is the most disabling feature of fibrodysplasia ossificans progressiva, an ultra-rare genetic disorder for which there is currently no prevention or treatment. Most patients with this disease harbor a heterozygous activating mutation (c.617 G > A;p.R206H) in ACVR1. Here, we identify recombinant AAV9 as the most effective serotype for transduction of the major cells-of-origin of heterotopic ossification. We use AAV9 delivery for gene replacement by expression of codon-optimized human ACVR1, ACVR1R206H allele-specific silencing by AAV-compatible artificial miRNA and a combination of gene replacement and silencing. In mouse skeletal cells harboring a conditional knock-in allele of human mutant ACVR1 and in patient-derived induced pluripotent stem cells, AAV gene therapy ablated aberrant Activin A signaling and chondrogenic and osteogenic differentiation. In Acvr1(R206H) knock-in mice treated locally in early adulthood or systemically at birth, trauma-induced endochondral bone formation was markedly reduced, while inflammation and fibroproliferative responses remained largely intact in the injured muscle. Remarkably, spontaneous heterotopic ossification also substantially decreased in in Acvr1(R206H) knock-in mice treated systemically at birth or in early adulthood. Collectively, we develop promising gene therapeutics that can prevent disabling heterotopic ossification in mice, supporting clinical translation to patients with fibrodysplasia ossificans progressiva.


Potential heating caused by intraparenchymal intracranial pressure transducers in a 3-tesla magnetic resonance imaging system using a body radiofrequency resonator: assessment of the Codman MicroSensor Transducer.
Magnetic resonance imaging and spectroscopy may provide important clinical information in the acute stages of brain injury. For this to occur it must be ensured that intracranial pressure (ICP) monitoring devices are safe to bring into the MR imaging suite. The authors tested a Codman MicroSensor ICP Transducer (Codman & Shurtleff, Inc.) within a 3-T MR imaging system using the transmit body coil and receive-only coils and the transmit-and-receive head coil. Extreme and rapid heating of 64 degrees C was noted with the transducer wire in certain positions when using the transmit body coil and receive-only head coil. This is consistent with the phenomenon of resonance, and the probe was shown to have a distinct resonant response when coupled to HP 4195A Network Analyzer (Hewlett Packard). Coiling some of the transducer wire outside of the receive-only head coil reduced the generated current and so stopped the thermogenesis. This may be due to the introduction of a radiofrequency choke. The ICP transducer performed within clinically acceptable limits in both the static magnetic field and during imaging with high radiofrequency power when the excess wire was in this configuration. No heating was observed when a transmit-and-receive head coil was used. This study has shown when using a high-field magnet, the Codman ICP probe is MR conditional. That is, in the authors' system, it can be safely used with the transmit-and-receive head coil, but when using the transmit body coil the transducer wire must be coiled into concentric loops outside of the receive-only head coil.


Dopamine dysregulation syndrome in Parkinson's disease.
Dopamine replacement therapy in Parkinson's disease ameliorates motor symptoms. However, it has recently been recognized that a small sub-group of patients suffer motor and behavioural disturbances attributable to taking quantities of medication well beyond the dose required to treat their motor disabilities. This review examines the phenomenology of dopamine dysregulation syndrome in relation to the current understanding of basal ganglia function and its impact on long-term management. Cortico-striato-thalamic circuits are implicated in the behavioural and motor disturbances associated with compulsive medication use in Parkinson's disease. Advances in understanding of the role of dopamine in psychostimulant addiction are important in helping to understand dopamine dysregulation. Recognition of dopamine dysregulation syndrome and characterization of its phenomenology supports the notion that the medication used to treat Parkinson's disease can disrupt basal ganglia mediated motor and behavioural functioning. Refinement of clinical strategies to predict, identify and manage this syndrome will aid the future treatment of motor and non-motor complications of Parkinson's disease.


Khat: pharmacognostical aspects.
A survey was made of the early literature on the production of khat. A botanical and micromorphological examination of 15 samples of Catha edulis was carried out and the findings were compared with data from the earlier literature on the subject. Based on earlier and present observations, the vital organs (leaves, flowers, fruit and seeds) are described, with illustrations, to assist in the identification of khat.


Obesity and ovarian cancer risk: A systematic review.
The association between obesity and ovarian cancer risk has been extensively investigated, but studies have yielded inconsistent findings. This review aims to summarise and discuss the evidence generated to date. Articles published in English prior to August 2016 were retrieved from PubMed. Keywords included obesity, overweight, body size, body mass index, waist-hip ratio, waist circumference, body weight, ovarian cancer, ovarian carcinoma, ovarian neoplasm, and ovarian tumour. Eligible studies compared two or more groups of women, with at least one group in the overweight or obese category and one comprising normal weight controls. Summary data in the form of relative risk, hazard ratio, or odds ratio for each comparison group from individual studies were collated and reviewed. Forty-three studies were included in the final analysis, with a total of 3,491,943 participants. All studies included body mass index as an exposure measure, and a majority relied on self-reported measures from participants; 14 studies found a statistically significant positive association between ovarian cancer risk and higher body mass index, 26 studies found no significant association, and 3 studies found a negative association between ovarian cancer risk and higher body mass index. This review concludes that there is limited, inconsistent evidence of a positive association between obesity and ovarian cancer risk.


Optimization of an acoustic black hole vibration absorber at the end of a cantilever beam.
Structures whose thickness follow a power law profile exhibit the "acoustic black hole" (ABH) effect and can be used for effective vibration reduction. However, it is difficult to know a priori what constitutes the best design. A new block matrix formulation of the transfer matrix method is developed for use in the optimization of an ABH vibration absorber at the end of a cantilever beam. Results indicate that introduction of the ABH significantly alters the dynamics of the beam, which must be considered in determining the optimal design for a given vibration reduction problem.


Fused Triazinobenzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, and In Silico and In Vitro Biological Activity.
[1,3,5]Triazino[1,2-a]benzimidazole-2-amines bearing heterocyclic moiety in 4-position were synthesized. The compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. The molecular geometry and electron structure of these molecules were theoretically studied using density functional theory (DFT) methods. The molecular structure of the synthesized fused triazinobenzimidazole was confirmed to correspond to the 3,4-dihydrotriazinobenzimidazole structure through the analysis of spectroscopic NMR data and DFT calculations. The antinematodic activity was evaluated in vitro on isolated encapsulated muscle larvae (ML) of Trichinella spiralis. The results showed that the tested triazinobenzimidazoles exhibit significantly higher efficiency than the conventional drug used to treat trichinosis, albendazole, at a concentration of 50 μg/mL. The compound 3c substituted with a thiophen-2-yl moiety exhibited the highest anthelmintic activity, with a larvicidal effect of 58.41% at a concentration of 50 μg/mL after 24 h of incubation. Following closely behind, the pyrrole analog 3f demonstrated 49.90% effectiveness at the same concentration. The preliminary structure-anti-T. spiralis activity relationship (SAR) of the analogues in the series was discussed. The cytotoxicity of the benzimidazole derivatives against two normal fibroblast cells (3T3 and CCL-1) and two cancer human cell lines (MCF-7 breast cancer cells and chronic myeloid leukemia cells AR-230) was evaluated using the MTT-dye reduction assay. The screening results indicated that the compounds showed no cytotoxicity against the tested cell lines. An in silico study of the physicochemical and pharmacokinetic characteristics of the novel synthesized fused triazinobenzimidazoles showed that they were characterized by a significant degree of drug-likeness and optimal properties for anthelmintic agents.


Genome Sequence of Talaromyces atroroseus, Which Produces Red Colorants for the Food Industry.
Talaromyces atroroseus is a known producer of Monascus colorants suitable for the food industry. Furthermore, genetic tools have been established that facilitate elucidation and engineering of its biosynthetic pathways. Here, we report the draft genome of a potential fungal cell factory, T. atroroseus IBT 11181 (CBS 123796).


Ab initio studies of 2,4-diamino triazine and its complexes with ligands: a model for inhibitor-active site interactions of dihydrofolate reductase.
The protonation energies of 2,4-diamino triazine, an inhibitor of the therapeutic target dihydrofolate reductase, has been calculated using ab initio (Hartree-Fock) calculations. It is found that N1 (see Fig. 1) exhibits the highest proton affinity (261.6 kcal/mol) by comparison with other inhibitor protonation sites. The energies of binding of the formate ion and formamide (as models for the amino acid residues in the active site of dihydrofolate reductase) to neutral and protonated 2,4-diamino triazine are also obtained. The highest binding energies are featured by the complex formed from a formate attached to the N4 and N1 protonated forms of the triazine. However, as N4 has a comparatively low proton affinity (195.0 kcal/mol), it is unlikely that an interaction of this nature would prevail. On the other hand, the formate-protonated N1 interaction is similar to the structures identified by X-ray crystallography of enzyme-triazine complexes.


Evidence for a localization of [(3)H]nociceptin binding sites on medullar primary afferent fibers.
The ORL1 receptor (opioid receptor-like 1) and its endogenous ligand, nociceptin, are involved in nociperception. We have studied, in a deafferented animal model, the modification of medullar [(3)H]nociceptin binding site density. A rhizotomy was carried out in rats at the cervicothoracic level, and the dorsal afferent fibers from C5 to T1 were lesioned. Seven days after surgery, animals were sacrificed, and the binding of [(3)H]nociceptin (2 nM) was then performed on spinal cord sections. An autoradiographic analysis revealed a significant reduction (-18%) of [(3)H]nociceptin binding site density in the dorsal horn ipsilateral to the deafferentation compared with the contralateral side of the lesion. In the ventral horn, no significant difference (-5%) of binding was observed in the ipsilateral side of the deafferentation compared with the contralateral side. Thus, [(3)H]nociceptin binding sites appear to be located mainly on either interneurons or deutoneurons of the spinal cord, because the bulk of the labeling is spared by the lesion. However, the significant reduction of labeling that occurs on the dorsal part of the ipsilateral side to the lesion indicates that [(3)H]nociceptin binding sites are also present on these dorsal afferent fibers.


Metal Halide Scaffolded Assemblies of Organic Molecules with Enhanced Emission and Room Temperature Phosphorescence.
Ionically bonded organic metal halide hybrids have emerged as versatile multicomponent material systems exhibiting unique and useful properties. The unlimited combinations of organic cations and metal halides lead to the tremendous structural diversity of this class of materials, which could unlock many undiscovered properties of both organic cations and metal halides. Here we report the synthesis and characterization of a series benzoquinolinium (BZQ) metal halides with a general formula (BZQ)Pb2X5 (X = Cl, Br), in which metal halides form a unique two-dimensional (2D) structure. These BZQ metal halides are found to exhibit enhanced photoluminescence and stability as compared to the pristine BZQ halides, due to the scaffolding effects of 2D metal halides. Optical characterizations and theoretical calculations reveal that BZQ+ cations are responsible for the emissions in these hybrid materials. Changing the halide from Cl to Br introduces heavy atom effects, resulting in yellow room temperature phosphorescence (RTP) from BZQ+ cations.


Dispersive Dam-Break Flow of a Photon Fluid.
We investigate the temporal photonic analogue of the dam-break phenomenon for shallow water by exploiting a fiber optics setup. We clearly observe the decay of the steplike input (photonic dam) into a pair of oppositely propagating rarefaction wave and dispersive shock wave. Our results show evidence for a critical transition of the dispersive shock into a self-cavitating state. The detailed observation of the cavitating state dynamics allows for a fully quantitative test of the Whitham modulation theory applied to the universal defocusing nonlinear Schrödinger equation.


Growth of colorectal polyps: recovery and evaluation of unresected polyps of less than 10 mm, 1 year after detection.
Colonoscopic 1-year control of polyps of less than 10 mm left in situ was carried out in 103 (89%) of 116 originally examined patients. Analysis showed an 85% recovery: 91% and 81% for polyps of 5-9 mm and < 5 mm, respectively. The recovery was significantly related to size and localization, whereas the growth rate was inversely correlated to the originally measured diameter. A linear relationship was demonstrated between anus-to-polyp distances 1 year apart, with a normalized agreement index of 0.70. In only 1 of 189 polyps, an increase of diameter to > 10 mm was demonstrated. The 79 new polyps in 52 (50%) of the patients were significantly smaller, more often right-sided, and related to multiplicity of polyps at the initial examination but not to growth of recovered polyps or cleansing status. An acceptable recovery and growth rate of polyps < 10 mm seems to justify the continuation of the study for the remaining 2 years.


Possible role of genetic factor(s) on age-related increase of peripheral CD4+CD8+ double positive T cells in cynomolgus monkeys.
Mature TCR alpha beta T cells in peripheral blood are generally classified into either CD4 single positive (sp) T cells or CD8sp T cells. Several studies demonstrated that considerable amounts of CD4+CD8+ double positive (DP) T cells exist in peripheral blood of human and several animals. In particular, we previously reported that peripheral DP T cells increase in an age-related manner in cynomolgus monkeys (Macaca fascicularis), but the finding that DP T cells in some aged monkeys were maintained at a low proportion (under 5%), suggests that the increase in peripheral DP T cells might be genetically controlled in cynomolgus monkeys. To test this hypothesis, 24 families were randomly selected and used in a formal genetic analysis of the proportion of DP T cells. Parents and offspring in selected families were classified into DP-High and DP-Low groups based on a 5% cutoff level of DP T cells. The cutoff value was set by analysis of the distribution of the proportion of DP T cells. Nine out of 13 offspring (69.2%) with DP-High x DP-High parents belonged to the DP-High group, whereas three out of nine offspring (33.3%) belonged to DP-High group in the case of DP-High x DP-Low mating pairs. No offspring (0%) of two offspring with DP-Low x DP-Low parents belonged to the DP-High group. In addition, heritability (h2: narrow sense) obtained from the regression coefficient of offspring on mid-parent values was 0.54 +/- 0.19. Both findings suggest that increases in DP T cells in cynomolgus monkeys may be genetically controlled.


The association between body mass index and risk of obstructive sleep apnea among patients with HIV.
Although several studies show a positive association between body mass index (BMI) and a higher risk of obstructive sleep apnea (OSA) in the general population, there are limited data on that in patients living with HIV (PLHIV). The objective of the current study is to determine the prevalence of high risk for OSA and the association between BMI and OSA in PLHIV. The study was conducted on 316 confirmed HIV cases aged ≥ 18 years who attended consulting centers in Tehran during 2019. For the diagnosis of OSA we used the Persian version of the modified Berlin questionnaire that includes ten questions broken down into three categories. A high risk for breathing problems was defined if the total score is ≥ 2. Logistic regression models were used to evaluate the association between BMI and OSA risk groups. Among PLHIV, 52.1% of men and 41.6% of women were considered as high risk for breathing problems during sleep at the time of the study. Patients with a higher risk for breathing problems had significantly higher BMI levels compared to those categorized as low-risk levels (25.2 vs. 24.3 kg/m2). Each unit increase in the BMI increased the odds of being high risk for OSA by 6% in the multivariable model. (odds ratio [OR]: 95% confidence interval [CI]: 1.06: 1.01-1.13). Considering BMI categories, compared to the normal weight, being obese (BMI ≥ 30 kg/m2) increased the high risk for OSA (OR [95% CI]: 2.54 [1.10-5.89]). We observed a significant association between general obesity and prevalence of OSA among PLHIV.


Molecular, Cytogenetic, and Hematological Analysis of Chronic Myeloid Leukemia Patients and Discovery of Two Novel Translocations.
Chronic myeloid leukemia (CML) is a disease of hematopoietic stem cells and is caused by the balanced translocations among the long arms of chromosomes 9 and 22, which are called the Philadelphia (Ph) chromosome. In this study, 131 CML patients were enrolled. Complete blood cell count was performed at the time of diagnosis for all the patients. Cytogenetic (karyotyping) examination using bone marrow samples was conducted on 76 CML patients for the confirmation of Ph-positive (9;22)(q34;q11) standard translocation, complex variant translocation, and additional chromosome abnormalities. FISH was performed on 38 patients for diagnostic purposes and on 39 patients for monitoring purposes. Twenty-two samples of CML patients were evaluated by reverse transcriptase PCR and real-time PCR for the patients who failed to respond against imatinib mesylate. In this study, 72 (54.96%) were males and 59 (45.03%) were females with a median age of 38.5 years. CBC values in the diagnosis process showed that 75 patients had high values of WBC being >100 × 103/μl, while 71 (58.01) patients exhibited reduced values of hemoglobin, i.e., <10.00 mg/dl, and high values of PLTs > 100 were observed in 40 (30.53%) patients. Cytogenetic results show that standard translocation was developed in 63 (82.89%), development of complex variant translocations in 4 (5.32%), additional chromosomal abnormalities (ACAs) in 3 (3.94%), and ACAs together with complex variant translocations in 1 (1.31%) patient. At the time of diagnosis, 61 (92.95%) patients were in the chronic phase, 4 (5.63%) were in the accelerated phase, and only 1 (1.40%) was in the blast crisis. Out of twenty-two patients, only 6 CML patients who were shifted from imatinib mesylate to nilotinib showed BCR-ABL-positive amplification. However, only 7 out of twenty-one patients exhibit BCR-ABL gene values ≥ 1 after three months of follow-up when analyzed by the quantitative real-time PCR. In conclusion, we found a novel five-way translocation 46XX,t(1;2;2;17;9;22)(p36.3,q21;q11.2,q21,q34,q11.2) and a novel four-way complex variant translocation 48XY,+8(8;17)(9;22),+der(22)(q11.2;q23)(q34;q11.2) in the accelerated phase.


Serum level of anti-α-enolase antibody in untreated systemic lupus erythematosus patients correlates with 24-hour urine protein and D-dimer.
Objective The objective of this report is to evaluate the prevalence and clinico-serological correlations of anti-α-enolase antibody (Ab) in patients with systemic lupus erythematosus (SLE). Methods Thirty-two untreated patients with SLE and 20 age- and sex-matched healthy controls were evaluated by rheumatologic examinations. The serum levels of anti-α-enolase Ab were measured by an enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical and serological markers of disease activity were measured by standard laboratory procedure. Results The serum levels of anti-α-enolase Ab in SLE patients were higher significantly than those in healthy controls. Moreover, patients with lupus nephritis displayed significantly higher levels of serum anti-α-enolase Ab than those without renal involvement. The serum anti-α-enolase Ab levels were positively correlated with serum whole IgG and 24-hour urine protein and negatively correlated with serum D-dimer level. Conclusion These data suggest that anti-α-enolase Ab associates with active renal disease in SLE and might reflect a state of active autoimmunity and fibrinolysis inhibition.


3-D bioprinting law regulation perspectives.
Achieved level of technical progress moves us closer and closer to practical use of 3-d bioprinting technologies in real life. Such perspective raise a wide variety of crucial legal issues from the acceptable model of regulation of the science and its' societal effects to problems of the commercialization of the technology and potential restrictions of its use. Some key points on concept of legal regulation of abovementioned sphere is a base of this study. Scientific discussion on 3-D bioprinting, European Union`s and US experience in patenting of 3-D bioprinting technologies, European Medicine Agency (EMA) or the US Food and Drug Administration (FDA) regulations, European Medical Technology Industry Association (EUCOMED) Acts. Article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. General debate of last few years comes down to an attempt to resolve hesitation between legal attempts for regulation of 3-D biobrinting and concept of complete prohibition of such activities. An adequate response to the mentioned challenge is a reasonable position between some aspects of prohibition and self-regulation, resulting in a moderate number of regulations and standards for developing and marketing. Such regulations may concern an intellectual property (IP) rights, regulation of distribution, premarket restrictions, control mechanism etc. Scientific approach and regulatory settlement of 3-D bioprinting sphere must unite to achieve a fair balance between the interests of humanity and of individuals - on the one hand, and development of science and business benefits for stakeholders - on the other. The main instruments for this must be balanced regulation of intellectual property (IP) rights, regulation of access and distribution, premarket restrictions, control mechanism etc.


Costs and effectiveness of alternative dog vaccination strategies to improve dog population coverage in rural and urban settings during a rabies outbreak.
Dog-rabies elimination programs have typically relied upon parenteral vaccination at central-point locations; however, dog-ownership practices, accessibility to hard-to-reach sub-populations, resource limitations, and logistics may impact a country's ability to reach the 70% coverage goal recommended by the World Organization for Animal Health (OIE) and World Health Organization (WHO). Here we report the cost-effectiveness of different dog-vaccination strategies during a dog-rabies outbreak in urban and peri-urban sections of Croix-des-Bouquets commune of the West Department, Haiti, in 2016. Three strategies, mobile static point (MSP), mobile static point with capture-vaccinate-release (MSP + CVR), and door-to-door vaccination with oral vaccination (DDV + ORV), were applied at five randomly assigned sites and assessed for free-roaming dog vaccination coverage and total population coverage. A total of 7065 dogs were vaccinated against rabies during the vaccination campaign. Overall, free-roaming dog vaccination coverage was estimated at 52% (47%-56%) for MSP, 53% (47%-60%) for DDV + ORV, and 65% (61%-69%) for MSP + CVR (differences with MSP and DDV + ORV significant at p < 0.01). Total dog vaccination coverage was 33% (95% CI: 26%-43%) for MSP, 49% (95% CI: 40%-61%) for MSP + CVR and 78% (77%-80%) for DDV + ORV (differences significant at p < 0.001). Overall, the least expensive campaign was MSP, with an estimated cost of about $2039 per day ($4078 total), and the most expensive was DDV + ORV with a cost of $3246 per day ($6492 total). Despite the relative high cost of an ORV bait, combining DDV and ORV was the most cost-effective strategy in our study ($1.97 per vaccinated dog), largely due to increased efficiency of the vaccinators to target less accessible dogs. Costs per vaccinated dog were $2.20 for MSP and $2.28 for MSP + CVR. We hope the results from this study will support the design and implementation of effective dog vaccination campaigns to achieve the goal of eliminating dog-mediated human rabies deaths by 2030.


Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts.
Background: Mesenchymal stromal cells (MSCs) and fibroblasts show similar morphology, surface marker expression, and proliferation, differentiation, and immunomodulatory capacities. These similarities not only blur their cell identities but also limit their application. Methods: We performed single-cell transcriptome sequencing of the human umbilical cord and foreskin MSCs (HuMSCs and FSMSCs) and extracted the single-cell transcriptome data of the bone marrow and adipose MSCs (BMSCs and ADMSCs) from the Gene Expression Omnibus (GEO) database. Then, we performed quality control, batch effect correction, integration, and clustering analysis of the integrated single-cell transcriptome data from the HuMSCs, FMSCs, BMSCs, and ADMSCs. The cell subsets were annotated based on the surface marker phenotypes for the MSCs (CD105 + , CD90 +, CD73 +, CD45 -, CD34 -, CD19 -, HLA-DRA -, and CD11b -), fibroblasts (VIM +, PECAM1 -, CD34 -, CD45 -, EPCAM -, and MYH11 -), and pericytes (CD146 +, PDGFRB +, PECAM1 -, CD34 -, and CD45 -). The expression levels of common fibroblast markers (ACTA2, FAP, PDGFRA, PDGFRB, S100A4, FN1, COL1A1, POSTN, DCN, COL1A2, FBLN2, COL1A2, DES, and CDH11) were also analyzed in all cell subsets. Finally, the gene expression profiles, differentiation status, and the enrichment status of various gene sets and regulons were compared between the cell subsets. Results: We demonstrated 15 distinct cell subsets in the integrated single-cell transcriptome sequencing data. Surface marker annotation demonstrated the MSC phenotype in 12 of the 15 cell subsets. C10 and C14 subsets demonstrated both the MSC and pericyte phenotypes. All 15 cell subsets demonstrated the fibroblast phenotype. C8, C12, and C13 subsets exclusively demonstrated the fibroblast phenotype. We identified 3,275 differentially expressed genes, 305 enriched gene sets, and 34 enriched regulons between the 15 cell subsets. The cell subsets that exclusively demonstrated the fibroblast phenotype represented less primitive and more differentiated cell types. Conclusion: Cell subsets with the MSC phenotype also demonstrated the fibroblast phenotype, but cell subsets with the fibroblast phenotype did not necessarily demonstrate the MSC phenotype, suggesting that MSCs represented a subclass of fibroblasts. We also demonstrated that the MSCs and fibroblasts represented highly heterogeneous populations with distinct cell subsets, which could be identified based on the differentially enriched gene sets and regulons that specify proliferating, differentiating, metabolic, and/or immunomodulatory functions.


Nonvisualized endometriosis at laparoscopy.
Apparently conflicting results have been reported regarding the incidence, and even the existence, of endometriosis in visually normal peritoneum. The present study was undertaken in view of the fact that the presence and incidence of nonvisualized deep and/or microscopic endometriosis may be of importance in patient management. One patient in this study demonstrated a 1-mm lesion of endometriosis beneath visually normal peritoneum. Two additional patients had cellular surface zones of possible endometrial stroma without a contiguous epithelial component. The results support the existence of unrecognized subperitoneal and microscopic surface endometriosis.


Physicochemical, molecular-orbital and electronic properties of acephate and methamidophos.
Methamidophos (Me) and its N-acetylated derivative, acephate (Ac), are water soluble insecticides that have similar insecticidal potency, but different mammalian toxicity. Me is a potent inhibitor, while Ac is a poor inhibitor of mammalian AChE (mAChE). At physiological pH, both insecticides exhibit similar accumulation in RBC, while Ac exhibits greater binding to plasma proteins than Me. These differential effects of Ac and Me are attributed to the differences in their physicochemical, molecular-orbital and electronic properties. Ac and Me are freely soluble in aqueous solution, moderately soluble in ethyl-acetate (EtAct) and insoluble in n-hexane. The solubility of these insecticides in aqueous solution and the partitioning of these insecticides from aqueous solution into EtAct are independent of the pH of the aqueous solution. At pH 8, Me did not react with o-phthalaldehyde (a NH2 selective dye), but gamma-amino-butyric acid (pKa 10) did. Thus, despite the presence of an amino group, Ac and Me do not exhibit pH dependent solubility in aqueous and in organic solvents. Ac has two O atoms with non-bonding electrons (P = O delta- and C = O delta-) where P = O and C = O point in opposite directions. Me has only one O atom with non-bonding electrons (P = O delta-). However, because of charge translocation, the C = O group of Ac exists as C = O- and the P-NH3+ group of Me exists as P = NH2+ at a pH lower than their pKa. The P-N bond of Me, but not of Ac, is hydrolyzed at pH 2. Thus, the presence of an electron rich domain stabilizes Ac's P-N bond. The CH3S-P bond of both insecticides is similarly hydrolyzed at pH 11. This indicates that the two compounds are considerably similar except that Ac has an additional electron rich domain. At physiological pH, therefore, the functional differences between these insecticides may be due to the differences in their electronic structure. We propose that, similar to a previous model for cationic inhibitors of AChE (13), the P = O delta- group of Me forms hydrogen bonds within the oxyanion-hole causing the leaving group (-SCH3) to orient towards the "gorge" opening. This orientation allows the P atom of Me to interact with Ser200, resulting in the phosphorylation of the enzyme. For acephate, either P = O or C = O, but not both, interact within the oxyanion-hole. This destabilizes the binding of Ac to the active center, resulting in reduced AChE phosphorylation.


Dyskinesias: nursing care and surgical intervention.
The dyskinesia syndromes are a group of physically, socially and psychologically debilitating diseases. Many patients may be helped through medical management consisting of drugs, physical and speech therapy, and vocational rehabilitation. However, when medical management fails to palliate symptoms, surgical intervention may be the patient's alternative. The ultimate goal of therapy is to lead an improved quality of life. As a neurosurgical nurse, you have an important role in achieving that goal.


Interplay of psychosocial factors and the long-term course of adolescents with a substance use disorder.
This paper examines the association of psychosocial factors and long-term drug use behaviors (year-5.5) among adolescents with a substance dependence disorder. One group received treatment with a 12-Step approach (n = 159) and one group was on a waiting list (n = 62). Four psychosocial factors (deviant behavior, peer drug environment, psychological disturbance and family estrangement), as measured by a standardized self-report questionnaire, were examined as predictors across three time points (year-1, year-4 and year-5.5). Improved outcome across time was significantly associated with decreases in deviant behavior, peer drug environment and family estrangement. However, psychological disturbance was not associated with outcome. Also, we did not find an effect on outcome as a function of age, gender and race. Youth that received treatment, as opposed to the waiting list youth, generally revealed a more favorable outcome across time. Treatment implications of the study findings are discussed.


Delayed and Aberrant Presentation of VX2 Carcinoma in a Rabbit Model of Hepatic Neoplasia.
A socially-housed New Zealand white rabbit presented with a large subcutaneous mass on the ventral thorax approximately 11 mo after the intrahepatic delivery of a suspension of VX2 carcinoma cells to induce hepatocellular carcinoma as part of a nanoparticle study. The mass and closely associated axillary lymph node were removed en bloc. Immunohistochemical staining identified the mass as an undifferentiated carcinoma. The rabbit demonstrated no appreciable pathology at the study end point at 16 mo after VX2 inoculation. An additional rabbit from the same VX2 injection cohort was found at necropsy to have an unanticipated intraabdominal mass, also identified as an undifferentiated carcinoma. This case report summarizes the molecular analysis of both tumors through a novel PCR assay, which identified the delayed and aberrant onset of VX2 carcinoma in an extended timeframe not previously reported.


Basil (Ocimum basilicum) Landraces Can Be Used in a Water-Limited Environment.
Basil (Ocimum basilicum L.) is a member of the Labiatae family and is one of the most widely consumed aromatic and medicinal plants in many countries due to its numerous properties and uses. The objective of the study was to determine whether landraces are better adapted to water-limited environments compared to commercial cultivars. Irrigation levels and genotypes affected plant height and leaf area index, with 25% and 33% higher values observed under complete irrigation, respectively. Additionally, limited water availability resulted in a 20% reduction in dry matter yield and a 21% reduction in essential oil yield over the three years in all of the genotypes tested, specifically in the lower irrigation treatment (d40), compared to the control treatment (d100). The landraces that performed the best under limited water supply were Athos white spike (AWS) and Gigas white spike (GWS), indicating their suitability for environments with limited water resources. The results demonstrate that there are landraces that can be utilized in dryland climates with appropriate water management, enabling water conservation and utilization of fields in water-scarce areas for irrigation purposes.


Alteration of stomach microbiota compositions in the progression of gastritis induces nitric oxide in gastric cell.
Atrophic gastritis is considered to be an antecedent to intestinal metaplasia and gastric cancer. A previous study identified that Helicobacter pylori was absent at the severe atrophic gastritis stage, and alterations in the gastric microbial composition resembled those in gastric cancer. To explore the role of the bacteria absence of H. pylori in gastric carcinogenesis, in the current study, we compared the microbiota of clinically collected H. pylori-free gastric fluids from 30 patients with non-atrophic gastritis (N) and 22 patients with severe atrophic gastritis (S). We estimated the bacterial loads in the N and S groups by colony counting in culture agar as well as by measuring the concentration of the extracted DNA. The results showed a significant increase in bacterial load in patients with atrophic gastritis in comparison to non-atrophic gastritis. Then, we analyzed the microbial communities of the gastric fluids from all 52 patients using high-throughput sequencing of 16S rRNA amplicons. The Chao 1, Shannon and Simpson diversity indexes demonstrated that the bacterial richness and diversity were not significantly different between the N and S groups. Moreover, principal component analysis illustrated that the microbiomes from the S group were more scattered. Microbiota composition analysis showed that the entire dataset was clustered into 27 phyla, 61 classes, 106 orders, 177 families, 292 genera and 121 species. At the genus level, only the abundance of Prevotella was significantly different between the N and S groups. Further analysis showed that all the higher taxonomic categories were significantly different between the N and S groups. To assess the effects of the metabolic products of Prevotella spp. on gastric cell physiology, we treated the human gastric epithelial cell line AGS with acetic acid and monitored nitric oxide (NO) production. The results showed that acetic acid at low concentrations (0.5 and 5 µM) significantly inhibited AGS cells to secrete NO compared to phosphate buffer saline-treated control cells. These results suggest that the microbiota in non-atrophic gastritis may influence gastric epithelial cell physiology.


Stimulated exocytosis of endosomes in goldfish retinal bipolar neurons.
After exocytosis, synaptic vesicle components are selectively retrieved by clathrin-mediated endocytosis and then re-used in future rounds of transmitter release. Under some conditions, synaptic terminals in addition perform bulk endocytosis of large membranous sacs. Bulk endocytosis is less selective than clathrin-mediated endocytosis and probably internalizes components normally targeted to the plasma membrane. Nonetheless, this process plays a major role in some tonic ribbon-type synapses, which release neurotransmitter for prolonged periods of time. We show here, that large endosomes formed after strong and prolonged stimulation undergo stimulated exocytosis in retinal bipolar neurons. The result suggests how cells might return erroneously internalized components to the plasma membrane, and also demonstrates that synaptic vesicles are not the only neuronal organelle that stains with styryl dyes and undergoes stimulated exocytosis.


Biomechanical Characteristics on the Lower Extremity of Three Typical Yoga Manoeuvres.
This study was aimed at exploring the biomechanical characteristics of the lower extremity amongst three typical yoga manoeuvres. A total of thirteen experienced female yoga practitioners were recruited in the current study; they were all certified with the Yoga Alliance. A three-dimensional motion capture system with 10 cameras combined with four synchronised force plates was used to collect kinematics of the lower extremity and ground reactive force whilst the participants performed the crescent lunge pose, warrior II pose, and triangle pose. One-way repeated ANOVA was used in exploring the differences amongst the three yoga movements, and the significance was set to alpha < 0.05. The triangle pose performed the largest range of motion (ROM) of the hip (90.5° ± 22.9°), knee (68.8° ± 23.1°), and ankle (46.4° ± 11.3°) in the sagittal plane and the hip (54.8° ± 6.5°), knee (42.4° ± 12.8°), and ankle (4.8° ± 1.7°) in the frontal plane amongst the three manoeuvres (P < 0.05). No significant difference was found for the hip and ankle joint moment amongst the three manoeuvres (P > 0.05). Knee joint travelled into 9.5° of extension and slight adduction of 1.94° whilst expressing the largest knee joint adduction moments (0.30 ± 0.22 Nm/kg) in the triangle pose. The distribution of the angular impulse of the lower limb joints indicated that the hip joint contributed significantly the most in the sagittal and frontal planes of the three yoga manoeuvres (P < 0.05), ranging from 51.67% to 70.56%. Results indicated that triangle pose may be superior to the other two manoeuvres, which improved hip joint ROM, strength, and dynamic stability. However, knee injuries such as osteoarthritis (OA) should be considered because of the large knee extensor angle and adductor moments.


Psychosocial Predictors of Physical Activity Change Among College Students in an Obesity Prevention Trial.
Moderate-to-vigorous physical activity (MVPA) is critical for maintaining a healthy weight, although little is known about psychological barriers to maintaining MVPA in at-risk groups. Identifying characteristics associated with poor MVPA maintenance in obesity prevention programs could improve participant outcomes. Toward this end, we examined predictors of MVPA in an obesity prevention trial for college students at risk for weight gain (n = 333; 72% female, mean BMI = 23.4 kg/m2). Participants engaged in 1 of 3 weight control interventions and in 4 assessments over 12-month follow-up (ie, measured height/weight, self-reports of psychosocial characteristics, 4 days of accelerometer wear). Multilevel modeling analyses showed that across conditions, participants decreased total MVPA minutes per week over 12 months (B = -5.48, P < .01). Baseline self-report scores for both impulsiveness and cognitive dissonance regarding engaging in unhealthy behaviors negatively predicted MVPA over time. Participants higher (vs. lower) in baseline impulsiveness (B = -6.89, P = .03) and dissonance (B = -4.10, P = .04) began the study with more MVPA minutes, but showed sharper declines over time. Targeted MVPA-focused intervention for students who show elevated impulsiveness and cognitive dissonance may improve both MVPA and weight control outcomes for these individuals.


Progesterone suppresses triple-negative breast cancer growth and metastasis to the brain via membrane progesterone receptor α.
Progesterone plays an important role in mammary epithelial cell proliferation and differentiation. Evidence from experimental and clinical studies indicates that progesterone is a risk factor for breast cancer under certain conditions through binding nuclear progesterone receptor (PR). These mechanisms, however, are not applicable to triple-negative breast cancer (TNBC) due to the lack of PR in these cancers. In this study, we demonstrate that membrane progesterone receptor α (mPRα) is expressed in TNBC tissues and the expression level of mPRα is negatively associated with the TNM stage. We found that progesterone suppressed the growth, migration and invasion of mPRα+ human TNBC cells in vitro, which was neither mediated by PR nor by PR membrane component 1 (PGRMCl). Notably, these effects exerted by progesterone were significantly blocked by shRNA specific to mPRα. Moreover, the knockdown of mPRα expression impaired the inhibitory effects of progesterone on mPRα+ tumor growth and metastasis in vivo. These data collectively indicate that progesterone suppresses TNCB growth and metastasis via mPRα, which provides evidence of the anti-neoplastic effects of progesterone-mPRα pathway in the treatment of human TNBC.


Cyclooxygenase-2 and B-cell lymphoma-2 expression in cystitis glandularis and primary vesicle adenocarcinoma.
Although cystitis glandularis (CG) is a common benign urinary bladder epithelial abnormality, it remains unclear whether CG is a premalignant lesion. Cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) overexpression has recently been reported as a potential tumor initiator or promoter. We evaluated and compared COX-2 and Bcl-2 expression in CG, chronic cystitis (CC), and primary vesicle adenocarcinoma (ADC) tissues. We conducted a retrospective study to investigate COX-2 and Bcl-2 levels in CG and ADC. We obtained tissue samples from 75 patients (including 11 cases of CC, 30 typical cases of CG (CGTP), 30 cases of intestinal CG (CGIT), and 4 cases of ADC) between 1989 and 2009 from the Surgical Pathology Archives of the No. 2 People's Hospital of Zhenjiang, affiliated with Jiangsu University. COX-2 and Bcl-2 immunohistochemical staining was performed on all tissues. Nine normal bladder epithelial specimens were evaluated as control samples. Correlations between COX-2 and Bcl-2 expression in CG were also analyzed. COX-2 and Bcl-2 expression was higher in the ADC group compared to other groups (p < 0.05). COX-2 and Bcl-2 levels were higher in the CGIT group compared to the CGTP group (p = 0.000 for both). The CGIT and CGTP groups both showed higher COX-2 expression compared to the CC group (p = 0.000 for both). There was no difference in Bcl-2 expression between the CGTP and CC groups (p = 0.452). Additionally, the difference in COX-2 and Bcl-2 expression between the control and CC groups was also insignificant (p = 0.668 and p = 0.097, respectively). Finally, we found that COX-2 and Bcl-2 levels were positively related (r = 0.648, p = 0.000). COX-2 and Bcl-2 overexpression in the CG group suggests that CG, particularly the intestinal type, may be a premalignant lesion that converts into a tumor in the presence of carcinogens.


Sudden cardiac death: opportunities for prevention.
The evidence base for implantable cardioverter-defibrillator (ICD) therapy requires expansion of guidance/indications to allow UK physicians to treat a broader range of patients. The ICD clinical consultees to the National Institute for Health and Clinical Excellence (NICE) review current guidance/guidelines, explain the evidence base, and suggest a UK ICD implantation strategy.


Fine tuning of globin gene expression by DNA methylation.
Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the gamma(A) and gamma(G) genes are expressed in fetal liver, both are silenced in adult erythrocytes. In order to decipher the role of DNA methylation in this process, we generated a YAC transgenic mouse system that allowed us to control gamma(A) methylation during development. DNA methylation causes a 20-fold repression of gamma(A) both in non-erythroid and adult erythroid cells. In erythroid cells this modification works as a dominant mechanism to repress gamma gene expression, probably through changes in histone acetylation that prevent the binding of erythroid transcription factors to the promoter. These studies demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin locus. In addition, our findings provide a mechanism for understanding the high levels of gamma-globin transcription seen in patients with Hereditary Persistence of Fetal Hemoglobin, and help explain why 5azaC and butyrate compounds stimulate gamma-globin expression in patients with beta-hemoglobinopathies.


[Microsurgical facial nerve decompression for hemifacial spasm].
The results of a series of 8 patients with hemifacial spasm (HFS), treated with microsurgical vascular decompression (MVD) are reported. A magnetic resonance imaging (MRI) of the brain was performed in all patients prior to surgery. The presence of arterial hypertension (HT) was noted. MVD was performed through a retromastoid approach, and Gortex was interposed between the nerve and the conflicting vessel. The offending vessels found were: the antero-inferior cerebellar artery in 50% of the cases, the postero-inferior cerebellar artery in 25% and the vertebral artery in 25%. These findings were positively correlated with MRI in only 50% of cases. The surgical results were the following: total and immediate relief in 62.5% of cases, delayed relief in 25%, and partial relief in 12.5%. Neither failure, nor recurrence were noted. In terms of complications, two cases of persisting hearing loss, one case of transient hearing loss, and two cases of persisting facial palsy. Hypertension improved in 20% of cases. This study shows the success of MVD in the treatment of HFS. Intraoperative monitoring is helpful in reducing the complication rate. In our practice, the correlation between MRI findings and surgery was poor, as opposed to the results found in literature.


IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells.
Interferon-gamma (IFN-γ) is a major effector molecule of immunity and a common feature of tumors responding to immunotherapy. Active IFN-γ signaling can directly trigger apoptosis and cell cycle arrest in human cancer cells. However, the mechanisms underlying these actions remain unclear. Here, we report that IFN-γ rapidly increases protein synthesis and causes the unfolded protein response (UPR), as evidenced by the increased expression of glucose-regulated protein 78, activating transcription factor-4, and c/EBP homologous protein (CHOP) in cells treated with IFN-γ. The JAK1/2-STAT1 and AKT-mTOR signaling pathways are required for IFN-γ-induced UPR. Endoplasmic reticulum (ER) stress promotes autophagy and restores homeostasis. Surprisingly, in IFN-γ-treated cells, autophagy was impaired at the step of autophagosome-lysosomal fusion and caused by a significant decline in the expression of lysosomal membrane protein-1 and -2 (LAMP-1/LAMP-2). The ER stress inhibitor 4-PBA restored LAMP expression in IFN-γ-treated cells. IFN-γ stimulation activated the protein kinase-like ER kinase (PERK)-eukaryotic initiation factor 2a subunit (eIF2α) axis and caused a reduction in global protein synthesis. The PERK inhibitor, GSK2606414, partially restored global protein synthesis and LAMP expression in cells treated with IFN-γ. We further investigated the functional consequences of IFN-γ-induced ER stress. We show that inhibition of ER stress significantly prevents IFN-γ-triggered apoptosis. CHOP knockdown abrogated IFN-γ-mediated apoptosis. Inhibition of ER stress also restored cyclin D1 expression in IFN-γ-treated cells. Thus, ER stress and the UPR caused by IFN-γ represent novel mechanisms underlying IFN-γ-mediated anticancer effects. This study expands our understanding of IFN-γ-mediated signaling and its cellular actions in tumor cells.


Pairing Behavior of the Monogamous King Quail, Coturnix chinensis.
Animals with socially monogamous mating systems are valuable for discovering proximate mechanisms of prosocial behavior and close social relationships. Especially powerful are comparisons between related species that differ in monogamous tendency. Birds are the most socially monogamous vertebrates. Thus far most research on mechanisms of pairing has used zebra finches, which do not have a relative with a different mating system, however. The goal of the experiments reported here was to develop a new comparative avian system by studying the pairing behavior of a reportedly strongly monogamous quail, the king quail (Coturnix chinensis), a species in the same clade as the less monogamous Japanese quail (Coturnix japonica), the subject of much prior research. In Experiment 1 male-female pairs of king quail housed together were initially avoidant or aggressive but most rapidly progressed to allopreening and huddling. A separation-reunion paradigm reliably elicited both of these behaviors in males that had cohabited for one week. In Experiment 2 the allopreening and huddling behavior of males in cohabiting pairs was highly selective, and a majority of the males were aggressive toward a familiar female that was not the cohabitation partner. In Experiment 3 males were separated from their female cohabitation partners for 9-10 weeks and then given two-choice tests. All but one male spent more time near an unfamiliar female, which may have reflected aggression and shows recognition of and memory for the past pairing experience. Thus king quail show robust, selective and easy to measure pairing behavior that can be reliably elicited with simple separation-reunion testing procedures. Copulation is rarely seen during tests. The behavior of king quail is a striking contrast to that of Japanese quail, providing a new comparative system for discovering mechanisms of behavior related to close social relationships and monogamy.


Visceral leishmaniasis in a patient with diabetes mellitus type 2 and discrete bicytopenia.
An Austrian patient with diabetes mellitus type 2 developed visceral leishmaniasis after trips to Spain and Crete, presenting with slight bicytopenia, later developing severe pancytopenia. Travel history taking is important due to an extended incubation period. Coexistence of diabetes mellitus can impair T lymphocyte function and cause higher relapse rates.


The effect of intensive education on concordance with the Age-Related Eye Disease Study (AREDS) recommendations in a tertiary referral practice.
The Age-Related Eye Disease Study (AREDS) showed that supplementation with their formula led to a significant decrease in progression of age-related macular degeneration (AMD). This study aims to assess the effect of different education protocols on concordance with the trial recommendations in two retinal clinics. A prospective controlled survey of concordance with the AREDS recommendations in two retinal clinics was administered to 330 patients with AREDS category 3 or 4 AMD. The results were evaluated to assess the effect of differing levels of patient education. In clinic 1, there was a formal policy of giving the patient both verbal and written instructions and verbal repetition of these instructions from each staff member on each patient visit; in clinic 2, there was no specific education policy. Clinic 1 had a concordance rate of 81.6% and clinic 2 of 44.1%. There were no significant differences in the patient demographics between the two clinics. A high concordance rate can be achieved in clinical practice with rigorous patient education that includes a policy of having continual repetition of instructions.


A 28 year old lady with a pituitary mass.
We present a case of an atypical pituitary adenoma with prominent lymphocyte infiltration and germinal center formation. Histologically, the tumor revealed clusters of large pleomorphic cells with vesicular nuclei, prominent nucleoli, smudgy chromatin, and abundant eosinophilic cytoplasm. There was heavy lymphocyte infiltration and prominent germinal center formation. Mitoses were rare, and the Ki-67 index was 15%. The lymphocytes were composed of both CD3-positive T lymphocytes and CD20-positive B-cells. The diagnosis was atypical pituitary adenoma. Germinal centers have not previously been reported in these tumors. It is important to correlate histology and immunohistochemistry to differentiate this adenoma from other pituitary lesions with prominent lymphocyte infiltration, such as germinoma and lymphocytic hypophysitis.


A comparison of an enzyme immunoassay and cell culture for detection of Chlamydia trachomatis in genito-urinary specimens.
Chlamydia trachomatis infection is easy to treat but laborious to diagnose by culture. An antigen-detecting enzyme immunoassay (EIA; Chlamydiazyme, Abbott Laboratories, North Chicago, IL), suitable for testing many samples, was compared with the conventional iodine-stained, one-passage culture. A total of 471 duplicate samples from 218 men (urethra) and 128 women (urethra and cervix) attending a sexually transmitted disease clinic were examined by both tests. The overall sensitivity, specificity, and predictive value of positive and negative results were 80.3%, 96.7%, 86.4%, and 95.0%, respectively. No difference between male and female patients was observed. A remarkable difference between sensitivities of female urethral (60.0%) and cervical (95.5%) samples was found. This difference is clearly important in cases of women with urethral infection only (19% in our study) and points to the need for further improvement of this EIA.