Evidence of Oxidative Phosphorylation in Zebrafish Photoreceptor Outer Segments at Different Larval Stages.
Previous studies on purified bovine rod outer segments (OS) disks pointed to Oxidative Phosphorylation (OXPHOS) as being the most likely mechanism involved in ATP production, as yet not fully understood, to support the first phototransduction steps. Bovine and murine rod OS disks, devoid of mitochondria, would house respiratory chain complexes I to IV and ATP synthase, similar to mitochondria. Zebrafish ( Danio rerio) is a well-suited animal model to study vertebrate embryogenesis as well as the retina, morphologically and functionally similar to its human counterpart. The present article reports fluorescence and Transmission Electron Microscopy colocalization analyses of respiratory complexes I and IV and ATP synthase with zpr3, the rod OS marker, in adult and larval zebrafish retinas. MitoTracker Deep Red 633 staining and assays of complexes I and III-IV activity suggest that those proteins are active in OS. Results show that an extramitochondrial aerobic metabolism is active in the zebrafish OS at 4 and 10 days of larval development, as well as in adults, suggesting that it is probably maintained during embryogenesis. Data support the hypothesis of an extramitochondrial aerobic metabolism in the OS of zebrafish.


Chronic respiratory care and rehabilitation in France.
The development of chronic respiratory care in France faces the same problems of ageing population, technological advancement and budgeting difficulties as other industrially developed countries. We describe the intermediate and home-care systems for treatment of chronic respiratory diseases.


Detection of the human coronavirus 229E, HKU1, NL63, and OC43 between 2010 and 2013 in Yamagata, Japan.
The available literature on human coronaviruses (HCoVs) in Japan is limited to epidemiological studies conducted over a maximum of 1 year. We conducted a 4-year study of HCoVs by analyzing 4,342 respiratory specimens obtained in Yamagata, Japan, between January 2010 and December 2013. A pan-coronavirus reverse transcription-PCR screening assay was performed, and all HCoV-positive specimens were subsequently confirmed by sequencing of the PCR products. We detected in 332 (7.6%) HCoV strains during the study period, comprising 133 (3.1%) HCoV-NL63, 83 (1.9%) HCoV-HKU1, 78 (1.8%) HCoV-OC43, and 38 (0.9%) HCoV-229E strains. HCoV detection per year ranged from 3.5% to 9.7%. HCoVs were detected mainly in winter, with January (28.5%) and February (25.3%) 2011 and December 2012 (14.6%) being the only months in which HCoV-NL63 detection per month exceeded 10.0%. HCoV-HKU1 displayed clear biennial peaks in January (18.3%) and February (10.7%) 2010 and in February (18.8%) and March (14.7%) 2012. The peak detection of HCoV-OC43 was 13.6% in November 2010, while that of HCoV-229E was 10.8% in March 2013. Our results indicated that there may be annual variations in the circulation of individual HCoV strains. Further long-term surveillance is necessary to clarify HCoV prevalence and circulation patterns in Japan.


Influence of Selected Saccharomyces and Schizosaccharomyces Strains and Their Mixed Cultures on Chemical Composition of Apple Wines.
Currently in apple winemaking, pure cultures of Saccharomyces cerevisiae and S. bayanus strains are mainly used. The aim of this study was to determine the influence of Saccharomyces cerevisiae (Johannisberg Riesling - LOCK 105), S. bayanus (DSMZ 3774), S. paradoxus (CBS 7302), and Schizosaccharomyces pombe (DSMZ 70576) applied in pure and mixed cultures on the chemical composition and sensory profile of apple wines. Pasteurized Gloster apple musts with addition of sucrose (up to 22°Blg) were inoculated with specific volume (0.6 g dry weight per liter) of yeast pure or mixed cultures (in a ratio of 1:1, 1:1:1, or 1:1:1:1) and fermented for 28 d at 22 °C. The influence of pure/mixed culture on the chemical composition, volatile profile, and sensory properties of apple wines was determined using high-performance liquid chromatography (HPLC) and gas chromatography (GC) methods. All pure culture of yeasts used for the apple wines production are characterized by good enological profiles. S. bayanus and Sch. pombe are the most distinct to S. cerevisiae. S. bayanus strain increases the level of malic acid and carbonyl compounds in apple wines, whereas Sch. pombe highly deacidifies it and produces the most of glycerol, esters, and acetic acid. The wines obtained with these 2 species gained also, respectively, the best and the worse notes during sensory analysis. Mixed cultures (in most cases) produce greater amounts of ethanol, methanol, and volatile esters compared to pure cultures. The presence of S. bayanus in the mixed culture is beneficial for the quality of apple wines. Good understanding of the properties of yeasts and the procedures for their selection will make it easier to find strains that could improve the quality of wine. Since wine is formed by the action of a number of species and strains of yeasts, many authors have studied the effect of mixed cultures on the final quality of the product. Most of this research was focused on the effect of the inoculation of Saccharomyces yeast with other species on the aroma of wine. However, there is a little data on the fermentation using simultaneous inoculation of different strains of S. cerevisiae.


Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response.
A number of recent studies have suggested that the main functional role of the product of the immune response (Ir) genes is in the process of antigen recognition by the T lymphocyte. The observation in the accompanying report that the interaction of macrophage-associated antigen with immune T lymphocytes requires that both cells share histocompatibility antigens raised the question as to whether the macrophage played a role in the genetic control of the immune response or even if the macrophage were the primary cell in which the product of the Ir gene is expressed. In the current study, parental macrophages were pulsed with an antigen, the response to which is controlled by an Ir gene lacking in that parent; these macrophages were then mixed with T cells derived from the (nonresponder x responder)F(1) and the resultant stimulation was measured. No stimulation was seen when column-purified F(1) lymph node lymphocytes were mixed with antigen-pulsed macrophages from the nonresponder parent. However, when the highly reactive peritoneal exudate lymphocyte population was used as the indicator cells, parental macrophages pulsed with an antigen whose Ir gene they lacked were capable of initiating F(1) T-cell proliferation. The magnitude of stimulation was approximately 1/10 that seen when macrophages from either the responder parent or the F(1) were used. In order to explain this observation, we hypothesize that antigen recognition sites on the T lymphocyte are physically related to a macrophage-binding site and both are linked to the serologically determined histocompatibility antigens. Thus, parental macrophages pulsed with an antigen, whose Ir gene they lack, activate F(1) cells poorly because the recognition sites for the antigen are physically related to the macrophage-binding site of the responder parent while the main contacts between the cells are at the nonresponder binding sites. Experiments performed with alloantisera lend support to this hypothesis. Thus, when parental macrophages are pulsed with any antigen and added to F(1) T cells, an alloantiserum directed against parental histocompatibility antigens reacts with both the lymphocyte and the macrophage and thereby inhibits macrophage-lymphocyte interaction and abolishes antigen-induced lymphocyte transformation. When the alloantisera are directed at determinants present solely on the T lymphocyte, they only inhibit the recognition of antigens controlled by the Ir gene linked to the histocompatibility antigen against which they are directed. We conclude from these studies that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.


Decline of superoxide dismutase activity during antioxidant-induced apoptosis in HL-60 cells.
Possible changes in Mn-containing superoxide dismutase (MnSOD) and Cu- and Zn-containing superoxide dismutase (CuZnSOD) activity during the apoptosis of human promyelocytic leukemia HL-60 cells, induced by three antioxidants, were investigated. Agarose gel electrophoresis of the DNA isolated from cells treated with sodium ascorbate, gallic acid or epigallocatechin gallate (EGCG) showed the internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis. The optimum concentration for induction of DNA fragmentation was narrow and higher concentrations were rather inhibitory. Their effects were detected after 3 hours and reached a maximum level at 6 hours. Polyacrylamide gel electrophoresis and activity staining demonstrated that both MnSOD and CuZnSOD activities were significantly reduced at cytotoxic concentrations of all these compounds. Incubation of an intracellular MnSOD-enriched fraction with apoptosis-inducing concentrations of sodium ascorbate, gallic acid or EGCG did not significantly reduce the MnSOD activity, suggesting that their actions might be cell-mediated. These data suggest the mitochondrial dysfunction at the early stages of apoptosis.


Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis.
Genetic and epigenetic regulations are essential mechanisms that ensure proper early and subsequent mammalian programming of diverse cellular processes. These mechanisms affect transcriptional regulation, stem cell determination and cell cycle control, including senescence and aging. It is not surprising that perturbation of the exquisite balance between genetic and epigenetic regulation can lead to diverse diseases, including cancer. Histone covalent modifications and DNA methylation do not explain all epigenetic phenomena. We describe a previously unsuspected epigenetic factor and propose the incorporation of the 11-zinc finger CCCTC-binding factor, known as CTCF as a novel and multifunctional epigenetic regulator.


The ORFeome of Staphylococcus aureus v 1.1.
The bacterium Staphylococcus aureus causes significant morbidity and mortality in humans, primarily due to the emergence of strains that are resistant to antibiotics - notably methicillin-resistant S. aureus (MRSA) isolates. Development of effective strategies for the control and treatment of MRSA infections may best be achieved through 'omics' approaches, which first requires cloning the entire set of S. aureus' protein-encoding open reading frames (ORFs), or ORFeome. The complete genome sequence of S. aureus strain Mu50 has 2697 predicted protein-coding ORFs. Based on the sequence of this strain we designed PCR primers to construct from an S. aureus (non-MRSA) clinical isolate an ORFeome library that contains 2562 unique Gateway entry clones (95% coverage), each corresponding to a defined ORF. The high quality of the ORFeome library was verified by DNA sequencing and PCR amplification, and its functionality was demonstrated by expressing recombinant proteins and observing protein interactions in a yeast 2-hybrid homodimerization screen. This first ORFeome library for S. aureus provides an essential new tool for investigating the systems biology of this important pathogen.


Quality assurance in a neighborhood health center: dental services.
A method for assessing the quality of dental care in neighborhood health centers has been presented. The audit uses implicit review for the evaluation of the overall process of dental care and explicit review for the technical component of the clinical audit and the evaluation of the dental record. This combined approach is favored over a totally explicit audit because it is more flexible and efficient and less threatening to the dentist. Although the "soft" structure of this audit could be criticized, the major issue is that a useable, simple quality assurance mechanism has been successfully used to improved the quality of dental care. Modifications of criteria will certainly evolve as quality assurance mechanisms improve.


Rasburicase-induced haemolysis and methemoglobinemia: an ongoing issue.
We report a case of a 91-year-old Caucasian woman with a history of chronic lymphocytic leukaemia who developed acute hypoxic respiratory failure (AHRF) requiring intubation for less than 24 hours after receiving rasburicase. Laboratory workup was significant for methemoglobinemia and acute anaemia, and blood film demonstrated evidence of oxidative haemolysis with bite cells. The patient was given a presumptive diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency and was managed conservatively with successful resolution of AHRF and stabilisation of haemoglobin level. Seven days after admission, she passed away due to subsequent complications; hence, follow-up G6PD level could not be obtained. Haemolytic anaemia and methemoglobinemia in the setting of recent rasburicase administration should raise clinical suspicion for G6PD deficiency. In non-emergent cases, patients should be screened prior to receiving rasburicase regardless of risk factors. Because rasburicase is often needed emergently, patients at high risk of tumour lysis syndrome should be screened early for G6PD deficiency.


Advanced Oxygen Electrocatalyst for Air-Breathing Electrode in Zn-Air Batteries.
The electrochemical reduction of oxygen to water and the evolution of oxygen from water are two important electrode reactions extensively studied for the development of electrochemical energy conversion and storage technologies based on oxygen electrocatalysis. The development of an inexpensive, highly active, and durable nonprecious-metal-based oxygen electrocatalyst is indispensable for emerging energy technologies, including anion exchange membrane fuel cells, metal-air batteries (MABs), water electrolyzers, etc. The activity of an oxygen electrocatalyst largely decides the overall energy storage performance of these devices. Although the catalytic activities of Pt and Ru/Ir-based catalysts toward an oxygen reduction reaction (ORR) and an oxygen evolution reaction (OER) are known, the high cost and lack of durability limit their extensive use for practical applications. This review article highlights the oxygen electrocatalytic activity of the emerging non-Pt and non-Ru/Ir oxygen electrocatalysts including transition-metal-based random alloys, intermetallics, metal-coordinated nitrogen-doped carbon (M-N-C), and transition metal phosphides, nitrides, etc., for the development of an air-breathing electrode for aqueous primary and secondary zinc-air batteries (ZABs). Rational surface and chemical engineering of these electrocatalysts is required to achieve the desired oxygen electrocatalytic activity. The surface engineering increases the number of active sites, whereas the chemical engineering enhances the intrinsic activity of the catalyst. The encapsulation or integration of the active catalyst with undoped or heteroatom-doped carbon nanostructures affords an enhanced durability to the active catalyst. In many cases, the synergistic effect between the heteroatom-doped carbon matrix and the active catalyst plays an important role in controlling the catalytic activity. The ORR activity of these catalysts is evaluated in terms of onset potential, number of electrons transferred, limiting current density, and durability. The bifunctional oxygen electrocatalytic activity and ZAB performance, on the other hand, are measured in terms of potential gap between the ORR and OER, ΔE = Ej10OER - E1/2ORR, specific capacity, peak power density, open circuit voltage, voltaic efficiency, and charge-discharge cycling stability. The nonprecious metal electrocatalyst-based ZABs are very promising and they deliver high power density, specific capacity, and round-trip efficiency. The active site for oxygen electrocatalysis and challenges associated with carbon support is briefly addressed. Despite the considerable progress made with the emerging electrocatalysts in recent years, several issues are yet to be addressed to achieve the commercial potential of rechargeable ZAB for practical applications.


Effects of graded sucrose additions on taste preference, acceptability, glycemic index, and insulin response to butter beans.
Dried beans, because of their high-fiber content and low-glycemic index, are especially suitable for diabetic diets. Most South African bean recipes contain sucrose, and since a restriction of artificial sweeteners seems desirable, replacing sucrose would be impractical. Hence, we examined the effects of 10, 20, and 30% sucrose additions to cooked dried butter beans on taste preference and acceptability in 29 diabetic patients and 11 control subjects. The effect of sucrose additions on glycemic index and insulin response to butter beans was determined in control subjects. Both diabetic and control subjects preferred beans with sucrose additions (p less than 0.005). Additions of sucrose up to 20% of total carbohydrate had no adverse effects on glycemic index or insulin response of butter beans (p less than 0.05), which indicates that addition of moderate amounts of sucrose to a low glycemic index food may improve palatability without impairing the favorable effect on blood glucose and insulin response.


Inflammatory Myofibroblastic Tumor of the Orbit in a 5-Month-Old Infant.
Inflammatory myofibroblastic tumors are mesenchymal neoplasms composed of spindle cells and inflammatory infiltrate. The authors describe a 5-month-old infant with orbital inflammatory myofibroblastic tumor, the youngest patient currently reported in the literature. The histo-pathology, orbital apex location, and patient's age led to a chemotherapy-driven treatment using crizotinib with near-complete resolution of the tumor. [J Pediatr Ophthalmol Strabismus. 2022;59(2):e25-e28.].


In vivo suppression of precore mRNA synthesis is associated with mutations in the hepatitis B virus core promoter.
We have examined the in vivo effect of hepatitis B virus (HBV) core promoter mutations on the expression of precore mRNA and pregenomic RNA transcripts in the liver of 24 patients with chronic HBV infection, applying a novel transcript-specific RT-PCR assay. The double A1762T/G1764A mutation in the basic core promoter was detected in 11 cases. This mutation was in all cases associated with absence or low levels of precore mRNA transcripts without significantly affecting the levels of total core promoter-directed transcription in the liver of infected patients. Precore mRNA synthesis was suppressed by the A1762T/G1764A mutation regardless of the presence of the precore stop codon mutation G1896A, suggesting that in addition to downregulating an immunomodulatory protein this double basic core promoter mutation may also confer a replication advantage to the virus. Additional mutations detected in the core promoter may also contribute to the observed changes in precore mRNA levels. Our in vivo study shows therefore that the double A1762T/G1764A mutation is associated with the specific suppression of precore mRNA synthesis directed by the HBV core promoter.


Isoflavonoids production in callus culture of Pueraria tuberosa, the Indian kudzu.
Isoflavonoid contents of different plant parts and callus tissues of the Indian Kudzu, Pueraria tuberosa (Roxb.ex.Willd.) DC are presented. The initial cultures were slow growing, associated with browning of the tissues. The production of four isoflavonoids (puerarin, genistin, genistein and daidzein) in the callus cultures of P. tuberosa was studied by manipulating the plant growth regulators and sucrose concentration in the medium. Organogenesis was not recorded in callus on any of these treatments. Tuber and stem accumulated puerarin, a glycoside of daidzein, at high amounts, 0.65% and 0.054% respectively. However, the daidzein content of the callus tissues grown on Murashige and Skoog medium containing BA (20.9 microM) and sucrose (60 gl(-1)) was significantly higher (0.056%) than in vivo plant material (0.02%) and other comparable culture systems like Genista and Pueraria lobata.


Glycodelin in reproductive endocrinology and hormone-related cancer.
Glycodelin is an endocrine-regulated glycoprotein that has significant effects on immune cells, apoptosis, reproduction, cell adhesion, differentiation and cancer. In reproduction, glycodelin contributes to capacitation and immunoprotection of spermatozoa, and it modulates sperm-oocyte binding, acrosome reaction and implantation. In endocrine-related cancer, the differentiation inducing effects of glycodelin are accompanied by growth restriction of malignant cells, decreased expression of oncogenes, increased expression of tumour suppressor genes and morphological reversion of the malignant phenotype. This review features these properties and clinical connections, highlighting the role of glycosylation in biological actions.


IQ in early adulthood and later risk of death by homicide: cohort study of 1 million men.
Risk factors for homicide are emerging; however, the predictive value of IQ, for which there is a strong prima facie case, has yet to be examined. To examine the association between IQ and risk of death by homicide. A cohort of 968 846 men, aged 18-19 years, were administered an IQ test battery at military conscription and then followed for mortality experience over two decades. There were 191 deaths due to homicide during follow-up. In age-adjusted analyses, a high total IQ test score was associated with a reduced rate of homicide (hazard ratio (HR) per standard deviation increase in IQ score=0.49, 95% CI 0.42-0.57). A step-wise gradient was apparent across the three IQ groups (P-value for trend <0.001). After adjustment for indicators of socio-economic position and illness at conscription, this gradient was marginally attenuated (HR=0.57, 95% CI 0.49-0.67). High IQ test scores in early adulthood were associated with a reduced risk of death by homicide.


Development of fabrication system of prostheses using electric discharge machining.
This paper outlines the principles and uses of electric discharge machining (EDM) in the fabrication of prostheses. The three areas of use of EDM are classified as supplementary use, direct fabrication of crowns and bridges and fabrication of titanium copings using a CAD/CAM process. The problems associated with the use of EDM in each area are discussed and the methods employed to overcome these problems are described. The application of numerically controlled (NC) EDM to prosthodontic work is found to be promising. Further refinement and development are necessary before EDM can be widely accepted as a means of fabricating prostheses.


Synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- 3-substituted pyrrolidine-2,5-dione derivatives.
The synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- succinimides [I-XXII] differently substituted at the position-3 of imide ring have been described. The profile of pharmacological activity of these compounds was examined by a maximal electroshock (MES) and pentylenetetrazole (scPTZ) tests, whereas their neurotoxicity was determined using a rotarod screen. The results obtained revealed that the anticonvulsant activity depended mainly on the kind of substituents at the position-3 of pyrrolidine-2,5-dione ring. The most active were 3,3-dialkyl-pyrrolidine-2,5-diones [IX-XVIII] as well as compounds with 3-methylcyclohexane moiety as a spiro nucleus at position-3 of the imide ring [I-IV]. The 3-cyclohexylsuccinimides [V-VIII] with cyclohexane ring as a flexible fragment were less active, whereas unsubstituated derivatives [XIX-XXII] were devoid of activity in both tests applied. In addition, the anti-seizure protection depended on the position of methyl group at the pyridine moiety. The most potent were compounds with the methyl substituent at the position-4 [II, VI, XVII] or -6 [XI, XIV]. It should be noted, that in the whole series the most active was 1-(4-methyl-2-pyridinyl)-3-cyclohexyl-pyrrolidne-2,5-dione [VI], which showed the anti-scPTZ protection at the dose of 30 mg/kg.


Placenta percreta presenting in the first trimester: review of the literature.
Placenta percreta complicating pregnancy in the first trimester is extremely rare, and only a few cases have been reported in the literature. We recently reported on a patient with risk factors for placenta percreta that presented as first trimester fetal demise, unresponsive to medical management with prostaglandin. The patient required an emergency hysterectomy to control the bleeding after uterine curettage, and was complicated by severe consumption coagulopathy. This rare entity can lead to significant mortality and morbidity, particularly in the background of increased prevalence of the disease and its associated risk factors, and the large number of spontaneous and induced abortions performed worldwide. Therefore, we also reviewed all reported cases of first-trimester placenta percreta in the literature to increase the awareness of physicians and to highlight the clinical features and essentials of the management.


Incidence of manifest glaucoma.
The incidence of manifest glaucoma was determined by means of repeated automatic perimetry in a defined general population. It was estimated at 0.24% per year. It was largely independent of age but higher in women than in men and higher in the countryside than in the villages. In fact the incidence of manifest glaucoma was five times higher among women in the countryside than among men in the villages.


[Transient neonatal diabetes associated with uniparental isodisomy of chromosome 6].
A female neonate was born after a 37.4-week pregnancy to a healthy primipara. There was a family history of diabetes on the father's side. The neonate's birth weight was 1,955 g and she was 43 cm long. Physical examination showed bilateral palpebral edema, macroglossia, umbilical hernia and abdominal distension. At 29 hours of life she presented hyperglycemia without acidosis or ketosis. Insulin treatment was started and maintained intermittently until 38 days of life. The patient presented anemia from the second day of life, which required iron therapy and blood transfusion one month after birth. The karyotype was 46, XX with paternal uniparental isodisomy of chromosome 6. Paternal uniparental isodisomy of chromosome 6 has been described as the pathogenic mechanism of transient neonatal diabetes, which provides evidence for an imprinted gene exclusively of paternal expression. In paternal isodisomy (as in regional duplications) there is overexpression due to the existence of two functional copies of the gene, which is responsible for transient neonatal diabetes mellitus. Transient neonatal diabetes associated with macroglossia, umbilical hernia and anemia has been described in only a few cases.


Transcriptional Regulation in the Immune System: One Cell at a Time.
Transcriptional regulation of cells in the immune system must be strictly controlled at multiple levels to ensure that a proper immune response is elicited only when required. Analysis in bulk, or ensemble of cells, provides a wealth of important information leading to a better understanding of the various molecular steps and mechanisms involved in regulating gene expression in immune cells. However, given the substantial heterogeneity of these cells, it is imperative now to decipher these mechanisms at a single cell level. Here I bring together several recent examples to review our understanding of transcriptional regulation of the immune system via single cell analysis and to further illustrate the immense power of such analyses to interrogate immune cell heterogeneity.


iSeeRNA: identification of long intergenic non-coding RNA transcripts from transcriptome sequencing data.
Long intergenic non-coding RNAs (lincRNAs) are emerging as a novel class of non-coding RNAs and potent gene regulators. High-throughput RNA-sequencing combined with de novo assembly promises quantity discovery of novel transcripts. However, the identification of lincRNAs from thousands of assembled transcripts is still challenging due to the difficulties of separating them from protein coding transcripts (PCTs). We have implemented iSeeRNA, a support vector machine (SVM)-based classifier for the identification of lincRNAs. iSeeRNA shows better performance compared to other software. A public available webserver for iSeeRNA is also provided for small size dataset. iSeeRNA demonstrates high prediction accuracy and runs several magnitudes faster than other similar programs. It can be integrated into the transcriptome data analysis pipelines or run as a web server, thus offering a valuable tool for lincRNA study.


Effect of amaranth leaves on dimethylhydrazine-induced changes in multicomponent antioxidant system of rat liver.
Effect of prefeeding dehydrated amaranth (A. gangeticus) leaves at 10 and 20% levels on a chemical toxicant, dimethylhydrazine (DMH)-induced free radical stress in rat liver was evaluated. DMH-induced rise in hepatic malondialdehyde (MDA), was diminished by AL. AL intake resulted in a significant increase in hepatic glutathione (GSH). The feeding of AL at 10% level increased the hepatic glucose-6-phosphate dehydrogenase (G-6-PDH) activity, while that at 20% level increased the hepatic glutathione reductase (GSSGR) as well, in addition to G-6-PDH. Amaranth leaves at 10 and 20% levels of feeding diminished the hepatic superoxide dismutase and glutathione peroxidase (GSH-Px) activities. DMH influenced adversely the hepatic antioxidant enzyme activities. Simultaneous administration of DMH and feeding of AL enhanced the DMH-induced decrease in hepatic GSH-Px. DMH enhanced formation of micronuclei was reverted significantly by AL intake. Hence, it was concluded that the consumption of AL at 20% level reduced DMH-induced impaired antioxidant status in rat liver.


A Therapeutic and Diagnostic Multidisciplinary Pathway for Merkel Cell Carcinoma Patients.
Merkel Cell Carcinoma (MCC) is a highly aggressive neuroendocrine neoplasm of the skin. Due to its rarity, the management of MCC is not standardized across centers. In this article, we present the experience of the Veneto region in the North-East of Italy, where a committee of skin cancer experts has proposed a clinical pathway for the diagnosis and treatment of MCC. Putting together the evidence available in the international literature, we outlined the best approach to the management of patients affected with this malignancy step- by- step for each possible clinical situation. Crucial in this pathway is the role of the multidisciplinary team to deal with the lack of robust information on each aspect of the management of this disease.


Molecular approaches to validate disinfectants against human hepatitis B virus.
Disinfection is an important measure to prevent hepatitis B virus (HBV) transmission by instruments. However, virucidal testing of disinfectants against HBV is difficult, because no simple quantitative infectivity assay exists. Since molecular changes of viral epitopes and the genome may indicate virus inactivation, we measured the alteration of these constituents with 0.065% peracetic acid (PAA) for exposure times up to 1 h. Plasma of a chronic HBV carrier with 10(9) HBV genomes/ml served as viral source in the form of a 10% dilution or of a purified HB-antigen preparation. Alterations of HBV epitopes were analyzed with four monoclonal antibodies in an enzyme-linked immunosorbent assay. Changes of the HBV genomes were determined by the inability to amplify the target sequence with a quantitative real-time polymerase chain reaction, either of a short fragment (189 bp) or of the full-length (3,200 bp). The determination of the epitope and genome alteration was quantified as log10 reduction factor (RF) with the parallel line bioassay. Under a high protein load of 10% human plasma, PAA induced a HBV genome alteration of RF = 1.5 after an exposure time of 60 min. Similar RFs were seen with the four HB epitopes. Without protein load, the alteration of these epitopes amounted to a RF of more than 3.5 within 30 min. Such inhibition of PAA activity by protein load was also seen in the virucidal tests with parvovirus. Although the RF were higher in the virucidal tests, the time-dependent dose-response curves for the epitope and genome alteration and for the infectivity inactivation followed the same inactivation kinetics. The molecular alteration and disintegration epitope and genome test may therefore be suitable to measure antiviral activity of disinfectants against HBV.


An Effective Sodium-Dependent Glucose Transporter 2 Inhibition, Canagliflozin, Prevents Development of Hypertensive Heart Failure in Dahl Salt-Sensitive Rats.
Background: The aim of the study was to investigate the protective effect of canagliflozin (CANA) on myocardial metabolism and heart under stress overload and to further explore its possible molecular mechanism. Methods: High-salt diet was used to induce heart failure with preserved ejection fraction (HFpEF), and then, the physical and physiological indicators were measured. The cardiac function was evaluated by echocardiography and related indicators. Masson trichrome staining, wheat germ agglutinin, and immunohistochemical staining were conducted for histology analysis. Meanwhile, oxidative stress and cardiac ATP production were also determined. PCR and Western blotting were used for quantitative detection of related genes and proteins. Comprehensive metabolomics and proteomics were employed for metabolic analysis and protein expression analysis. Results: In this study, CANA showed diuretic, hypotensive, weight loss, and increased intake of food and water. Dahl salt-sensitive (DSS) rats fed with a diet containing 8% NaCl AIN-76A developed left ventricular remodeling and diastolic dysfunction caused by hypertension. After CANA treatment, cardiac hypertrophy and fibrosis were reduced, and the left ventricular diastolic function was improved. Metabolomics and proteomics data confirmed that CANA reduced myocardial glucose metabolism and increased fatty acid metabolism and ketogenesis in DSS rats, normalizing myocardial metabolism and reducing the myocardial oxidative stress. Mechanistically, CANA upregulated p-adenosine 5'-monophosphate-activated protein kinase (p-AMPK) and sirtuin 1 (SIRT1) and significantly induced the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a). Conclusion: CANA can improve myocardial hypertrophy, fibrosis, and left ventricular diastolic dysfunction induced by hypertension in DSS rats, possibly through the activation of the AMPK/SIRT1/PGC-1a pathway to regulate energy metabolism and oxidative stress.


Carcinoma erysipeloides of laryngeal origin.
The term "carcinoma erysipeloides" (CE) designates an uncommon form of cutaneous metastasis. CE is most often associated with carcinoma of the breast. However, there have been reports of CE from carcinoma of the uterus, prostate, lung, ovary, stomach, tonsils, thyroid, pancreas, rectum, parotid glands and melanoma. To our knowledge, CE of laryngeal origin has not been previously reported. We describe a patient diagnosed with human immunodeficiency virus and hepatitis C virus coinfection who developed a supraglottic laryngeal squamous cell carcinoma and erythematous cutaneous lesions. A skin biopsy demonstrated invasion of dilated dermal lymphatics by clusters of atypical squamous cells with polymorphic nuclei and extensive infiltration of the dermis by tumor cells. The histology of the metastatic cells was similar to that of the laryngeal carcinoma.


Cross-Linguistic Word Recognition Development Among Chinese Children: A Multilevel Linear Mixed-Effects Modeling Approach.
The effects of psycholinguistic variables on reading development are critical to the evaluation of theories about the reading system. Although we know that the development of reading depends on both individual differences (endogenous) and item-level effects (exogenous), developmental research has focused mostly on average-level performance, ignoring individual differences. We investigated how the development of word recognition in Chinese children in both Chinese and English is affected by (a) item-level, exogenous effects (word frequency, radical consistency, and curricular grade level); (b) subject-level, endogenous individual differences (orthographic awareness and phonological awareness); and (c) their interactive effect. We tested native Chinese (Putonghua)-speaking children (n = 763) in grades 1 to 6 with both Chinese character and English word identification (lexical) decision tasks. Our findings show that (a) there were effects of both word frequency and age of acquisition in both Chinese and English, but these item-level effects generally weakened with increasing age; (b) individual differences in phonological and orthographic awareness each contributed to successful performance; and (c) in Chinese, item-level effects were weaker for more proficient readers. We contend that our findings can be explained by theoretical models that incorporate cumulative learning as the basis for development of item-level effects in the reading system.


Nonadenomatous polyps at CT colonography: prevalence, size distribution, and detection rates.
To prospectively investigate with computed tomographic (CT) colonography the prevalence and size distribution of nonadenomatous polyps in asymptomatic adults and to compare the detection rates of adenomatous and nonadenomatous polyps. A total of 1233 asymptomatic adults (mean age, 57.8 years; 505 women, 728 men) underwent same-day CT colonography and optical colonoscopy procedures. CT colonoscopy studies were interpreted prospectively with a primary three-dimensional approach immediately before optical colonoscopy. Statistical analysis was performed with the chi(2) test. Size, prevalence, and by-polyp detection differences were compared between adenomatous and nonadenomatous polyps. Seven hundred fifty-six (57.7%) colorectal polyps identified at optical colonoscopy in 410 (33.3%) patients were nonadenomatous; of these lesions, 622 (82.3%) were diminutive (</=5 mm). Nonadenomatous polyps accounted for 622 (64.4%) of 966 diminutive lesions and 134 (39.9%) of 344 polyps 6 mm or larger (P <.001). The prevalence rate for nonadenomatous polyps was 8.8% (109 of 1233 patients) and 2.0% (25 of 1233 patients) at 6- and 10-mm thresholds, respectively. CT colonography by-polyp sensitivity for nonadenomatous lesions was 73.1% (98 of 134 patients) and 73.3% (22 of 30 patients) at 6- and 10-mm thresholds, respectively, compared with 85.7% (180 of 210 patients) and 92.2% (47 of 51 patients) for adenomas (P <.01). In 1065 patients that did not have a 6-mm or larger adenoma at optical colonoscopy, CT colonography depicted a nonadenomatous polyp that was 6 mm or larger in 63 (5.9%) patients and a nonadenomatous polyp that was 10 mm or larger in 15 (1.4%) patients. More than 80% of nonadenomatous polyps were diminutive, but they accounted for nearly 40% of polyps that were 6 mm or larger. Fortunately, CT colonography is significantly (P <.01) less sensitive in the detection of lesions that have no malignant potential when compared with similar-sized adenomas that have malignant potential.


Extracorporeal membrane oxygenation for pediatric respiratory failure: five-year experience at the University of Pittsburgh.
To describe the etiology, respiratory severity of illness, and outcome in patients with pediatric respiratory failure who were treated with extracorporeal membrane oxygenation (ECMO). To identify predictors of death, and to compare our morbidity and mortality rates with those rates of a previously reported series of patients with pediatric respiratory failure managed conventionally. Survey, case series. Intensive care unit in a tertiary care pediatric hospital. Twenty-eight pediatric patients (3 wks to 20 yrs of age) who underwent ECMO for pediatric respiratory failure between 1985 and 1991. Thirteen (46%) of the 28 patients survived. The most common diagnoses were adult respiratory distress syndrome and nonspecific pneumonitis. Multiple organ system failure occurred in only four (14%) patients; most patients died of respiratory failure. The occurrence of persistent airleak during ECMO was significantly greater in nonsurvivors than in survivors. Furthermore, nonsurvivors had significantly less response to lung reexpansion maneuvers compared with survivors, as measured by a calculated compliance index (effective tidal volume/mean airway pressure x 100). The mortality rate was comparable with those rates of other published studies of conventionally managed and ECMO-treated patients with pediatric respiratory failure. Moreover, our patients appeared to exhibit more severe respiratory failure at the start of ECMO than those patients in other studies. ECMO appears to be a rational therapy for patients with pediatric respiratory failure who are likely to die with continued conventional management. Recovery of lung function by the end of the first week of ECMO may be a favorable prognostic indicator. Persistent airleak may be a nonfavorable prognostic indicator.


Disparities in post-mastectomy reconstruction use among American Indian and Alaska Native women.
American Indian/Alaska Native (AI/AN) breast cancer patients undergo post-mastectomy reconstruction (PMR) infrequently relative to Non-Hispanic White (NHW) patients. Factors associated with low PMR rates among AI/AN are poorly understood. We sought to describe factors associated with this disparity in surgical care. A retrospective cohort study of the National Cancer Database (2004 - 2017) identified AI/AN and NHW women, ages 18 - 64, who underwent mastectomy for stage 0 - III breast cancer. Patient characteristics, annual PMR rates, and factors associated with PMR were described with univariable analysis, the Cochran-Armitage test, and multivariable logistical regression. 414,036 NHW and 1,980 AI/AN met inclusion criteria. Relative to NHW, AI/AN had more comorbidities (20% vs 12% Charlson Comorbidity Index ≥ 1, p < 0.001), had non-private insurance (49% vs 20%, p < 0.001), and underwent unilateral mastectomy more frequently (69% vs 61%, p < 0.001). PMR rates increased over the study period, from 13% to 47% for AI/AN and from 29% to 62% for NHW (p <0.001). AI/AN race was independently associated with decreased likelihood of PMR (OR 0.62, 95% CI 0.56-0.69). Among AI/AN, decreased likelihood of PMR was significantly associated with older age at diagnosis, more remote year of diagnosis, advanced disease (tumor size > 5 cm, positive lymph nodes), unilateral mastectomy, non-private insurance, and lower educational attainment in patient's area of residence. PMR rates among AI/AN with stage 0 - III breast cancer have increased, yet remain significantly lower than among NHW. Further research should elicit AI/AN perspectives on PMR, and guide early breast cancer detection and treatment.


Parental Experiences of Neonatal Care: A Nationwide Study on Determinants of Excellence.
Infant- and family-centered developmental care can reduce adverse outcomes in both infants and parents. Parents' experiences of the care and staff treatment remain to be evaluated. Parents of infants admitted to neonatal units in Sweden from July 2020 to May 2022 responded to a questionnaire with standardized questions about in-hospital care. Exposures were hospital, gestational age, length of hospital stay, unit level, and bed density. The proportions of parents rating aspects of neonatal care as excellent, defined as five on a Likert scale, and the determinants of excellence were described. The results were benchmarked with ratings in adult somatic care. A total of 4,475/13,108 (34%) parents responded. The ratings of excellent care varied by question from 65% to 90%. The largest variation in excellence between neonatal units (range 43-80%) was found for "participation and involvement." The proportion of excellence was significantly lower among parents of extremely preterm infants. Confidence in the staff was lower in parents of extremely preterm infants than in parents of term infants (56% vs. 83%). Longer hospital stays affected the experience of neonatal care adversely, whereas level of care and bed density were overall unrelated to the parental experience. Parents in neonatal care rated the care as excellent to a higher extent than patients cared for in adult medicine. A majority of parents rated neonatal care in Sweden as excellent. The less frequent ratings of excellence among parents of extremely preterm infants indicate that more could be done to optimize parental involvement and support.


A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy.
A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations.


Evaluating Sleep in a Surgical Trauma Burn Intensive Care Unit: An Elusive Dilemma.
Evidence points to the adverse effects of sleep deprivation on a person's health. Despite decades of attention to the issue, patients, particularly those in the intensive care unit (ICU), continue to suffer. The purpose of this pilot study was to examine patients' perceptions of their sleep experience in the surgical trauma burn ICU and identify contributing factors. Patients were administered the 6-question Richards-Campbell Sleep Questionnaire (RCSQ) consisting of a 0- to 100-mm scale, with a low score indicating poor sleep quality. They were also asked an additional open-ended question. Sixty patients participated. Data revealed a low overall RCSQ score of 43.6 of 100. Of the 5 validated questions on the RCSQ, the question with the lowest mean (35.6) targeted depth of sleep. The question pertaining to falling asleep immediately scored the highest at 52.2. The open-ended question revealed that 37% reported "interruptions" as the reason for not sleeping. Pain was also cited as a factor by 30%, with 11.7% citing discomfort from the bed as an irritant. An additional 21.6% reported noise as the central reason, with "pumps/monitor" noise as the most frequent culprit at 62%. The pilot study results demonstrate that most participants perceived their sleep as poor in quality. These results direct targeted interventions that can be incorporated to reduce sleep deprivation in ICUs.


[Reasons for the explantation of posterior chamber lenses].
In this study we analysed the overall incidence and the types of complications seen after cataract surgery and implantation of posterior chamber intraocular lenses (PC-IOLs) based on a review of 1460 explanted PC-IOLs. Of these explanted PC-IOLs, 1072 (73.4%) were three-piece PMMA IOLs with Prolene haptics, 261 (17.9%) were one-piece all-PMMA IOLs, 81 (5.6%) were silicone IOLs and 46 (3.1%) were of various other designs (multifocal IOLs, disc IOLs etc.). The mean implant duration for all IOLs was 25.57 +/- 29.24 months. The two most important reasons for explantation were IOL decentration (622/1460, 42.6%) and inflammation (347/1460, 23.77%). There was no difference in reasons for explantation between one-piece and three-piece IOLs. Operative techniques such as "can opener" capsulotomy and sulcus fixation have more influence on IOL decentration than the IOL design alone. Modern operative techniques such as continuous curvilinear capsulorhexis, phacoemulsification and symmetrical in-the-bag fixation of "capsular IOLs" should decrease the explantation and complication rate in the future.


Quantitative superresolution microscopy reveals differences in nuclear DNA organization of multiple myeloma and monoclonal gammopathy of undetermined significance.
The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM.


Ingestion of carbohydrate or carbohydrate plus protein does not enhance performance during endurance exercise: a randomized crossover placebo-controlled clinical trial.
A beverage containing protein (PRO) and carbohydrate (CHO) may have an ergogenic effect on endurance performance. However, evidence regarding its efficacy on similar conditions to athletes' race day is still lacking. The objective of this study was to compare the effects of 3 different nutritional supplementation strategies on performance and muscle recovery in a duathlon protocol. Thirteen male athletes (29.7 ± 7.7 years) participated in 3 simulated Olympic-distance duathlon trials (SDTs) under 3 different, randomly assigned supplementation regimens: CHO drink (75 g CHO), isocaloric CHO plus PRO drink (60.5 g CHO and 14.5 g PRO), and placebo drink (PLA). Supplements were offered during the cycling bout. Blood samples were collected before, immediately after, and 24 h after each SDT for creatine kinase (CK) analysis. Isometric peak torque (PT) was measured before and 24 h after each SDT. The primary outcome measure was the time to complete the 5-km running section (t5km) at a self-selected pace. There was no difference in t5km between CHO (1270.3 ± 130.5 s), CHO+PRO (1267.2 ± 138.9 s), and PLA (1275.4 ± 120 s); p = 0.87, effect size (ES) ≤ 0.1. Pre-post changes for PT and CK were not significant for any of the 3 conditions (PT: p = 0.24, ES ≤ 0.4; CK: p = 0.32, ES = 0.3-1.04). For endurance sports lasting up to 2 h, with a pre-exercise meal containing CHO at 1.5 g·kg-1, supplementation with CHO or CHO+PRO does not offer additional benefits for performance and muscle recovery when compared with PLA.


Measurement of gastrointestinal intramucosal pH is a poor guide to tolerable levels of anemia during isovolemic hemodilution in a canine model of coronary stenosis.
To determine the relationship between gastrointestinal intramucosal pH and myocardial oxygenation during isovolemic hemodilution in dogs with critical coronary artery stenoses. Prospective sequential evaluation of ileal intramucosal pH and regional myocardial function of a critically perfused area of myocardial tissue in a canine model of normovolemic hemodilution. A research laboratory. Fifteen dogs. A micrometer snare was placed around a main coronary artery (8 left anterior descending artery, 7 right coronary artery). Three pairs of sonomicrometer crystals were placed in the heart to measure regional myocardial contraction. A gastrointestinal tonometer was placed in the ileum and used to measure luminal PCO2. This PCO2 value was used to calculate the ileal intramucosal pH. The animals underwent normovolemic hemodilution until myocardial ischemia occurred in the region supplied by the snared vessel. Measurements were continued for a further 40 minutes. Following instrumentation, stabilization, and critical constriction of a coronary vessel, percentage changes in systolic shortening of myocardial tissue in the region of critical perfusion were determined every 20 minutes. Ileal intramucosal pH and commonly measured cardiovascular variables were determined at the same time points. Myocardial ischemia occurred after 80 minutes of hemodilution, when the mean (+/- SD) hemoglobin concentration had fallen from a baseline level of 123 +/- 18 g/L to 82 +/- 14 g/L (P < .01). From the start of hemodilution to 40 minutes after myocardial ischemia occurred, there were no significant changes in heart rate, cardiac output, oxygen consumption, arterial acid-base balance, or arterial PCO2. Oxygen delivery decreased by approximately 45% (5.99 +/- 1.66 to 3.41 +/- 0.90 mL/kg per minute; P < .01) but there were no changes in ileal intramucosal pH (7.31 +/- 0.08 to 7.30 +/- 0.08; P = .90). Myocardium compromised by coronary stenosis is more sensitive to normovolemic hemodilution-induced ischemia than the normally perfused gut mucosa. This limits the potential utilization of the measurement of gastrointestinal intramucosal pH as a guide to tolerable levels of anemia in critically ill patients.


Class II treatment efficiency in maxillary premolar extraction and nonextraction protocols.
In this study, we compared the efficiency of nonextraction and 2-maxillary-premolar-extraction protocols in complete Class II malocclusion treatment. A sample of 112 records from patients with complete Class II malocclusion was divided into 2 groups with the following characteristics: group 1, comprising 43 patients treated nonextraction with an initial mean age of 12.63 years; and group 2, comprising 69 patients treated with extraction of 2 maxillary premolars with an initial mean age of 13.91 years. To compare the efficiency of each treatment protocol, the initial and final occlusal statuses were evaluated on dental casts with the peer assessment rating (PAR) index, and the treatment time of each group was calculated from the clinical charts. Treatment efficiency was calculated by the ratio between the percentage of PAR reduction and the treatment time. PAR scores, treatment times, and treatment protocols' efficiencies of the groups were compared with the t test. The 2-maxillary-premolar-extraction protocol had a smaller final PAR score, a greater percentage of PAR reduction, and greater treatment efficiency than the nonextraction protocol of complete Class II malocclusion. The 2-maxillary-premolar-extraction protocol has greater treatment efficiency than the nonextraction protocol of complete Class II malocclusion.


Swimming in circles: motion of bacteria near solid boundaries.
Near a solid boundary, Escherichia coli swims in clockwise circular motion. We provide a hydrodynamic model for this behavior. We show that circular trajectories are natural consequences of force-free and torque-free swimming and the hydrodynamic interactions with the boundary, which also leads to a hydrodynamic trapping of the cells close to the surface. We compare the results of the model with experimental data and obtain reasonable agreement. In particular, the radius of curvature of the trajectory is observed to increase with the length of the bacterium body.


Engraftment of HTLV-I-transformed human T-cell line into SCID mice with NK cell function.
HTLV-I-transformed human T-cell line, MT-2, has been reported to successfully proliferate in only the SCID mice with depletion of NK cell function. However, MT-2 cells could be engrafted into SCID mice possessing normal NK cell function in this study. MT-2 cells (5-7 x 10(7) cells) were intraperitoneally injected into SCID mice without the deletion of NK cell function. The SCID mice developed tumors in the peritoneal cavities 3 months after the inoculation of MT-2 cells. All tumors reacted to anti-HTLV-I p19 and anti-HLA-DR monoclonal antibodies by immunofluorescence assay and were also positive for the HTLV-I gene by PCR assay. DNA obtained from main organs in group of mice with or without tumors showed a high incidence of positive signals for HTLV-I gene by PCR assay.


Emerging technology for increasing glucosinolates in arugula and mustard greens.
Two plant species, arugula (Eruca sativa) and mustard (Brassica juncea) were field-grown under four soil management practices: soil mixed with municipal sewage sludge (SS), soil mixed with horse manure (HM), soil mixed with chicken manure (CM), and no-mulch bare soil (NM) to investigate the impact of soil amendments on the concentration of glucosinolates (GSLs) in their shoots. GSLs, hydrophilic plant secondary metabolites in arugula and mustard were extracted using boiling methanol and separated by adsorption on sephadex ion exchange disposable pipette tips filled with DEAE, a weak base, with a net positive charge that exchange anions such as GSLs. Quantification of GSLs was based on inactivation of arugula and mustard myrosinase and liberation of the glucose moiety from the GSLs molecule by addition of standardized myrosinase (thioglucosidase) and spectrophotometric quantification of the liberated glucose moiety. Overall, GSLs concentrations were significantly greater (1287 µg g-1 fresh shoots) in plants grown in SS compared to 929, 890, and 981 µg g-1 fresh shoots in plants grown in CM, HM, and NM soil, respectively. Results also revealed that mustard shoots contained greater concentrations of GSLs (974 µg g-1 fresh shoots) compared to arugula (651 µg g-1 fresh shoots).


[Porphyrias, a rare cause of acute abdominal pain].
The porphyrias are uncommon disorders caused by deficiencies of some enzymes of the heme biosynthetic pathway. Only four hepatic porphyrias are able to cause acute abdominal syndrome. In any case, the diagnosis requires the demonstration of increased urinary or stool excretion of accumulated metabolites of heme synthesis. Treatment is now possible and is able to reduce the burden of these metabolic diseases. The management implies also the identification of trigger exogenous factors such as oral contraceptives.


Association between hemodynamic profile during laboratory stress and ambulatory pulse pressure.
Hemodynamic responses underlying blood pressure reactivity to laboratory stress are theoretically linked to cardiovascular pathophysiology. The present study investigated whether a vascular response predicted ambulatory pulse pressure, a known risk factor for cardiovascular disease. A new model of hemodynamic profile, previously developed by the authors, was applied to 24-h ambulatory data from 30 female and 34 male healthy young adults. Of these, 40 were monitored during a naturalistic stressor (university examination). For females, hemodynamic profile significantly predicted nighttime systolic blood pressure, and 24-h, day-, and nighttime diastolic blood pressure, but not ambulatory pulse pressure. A vascular or mixed hemodynamic profile significantly predicted 24-h and daytime ambulatory pulse pressure in males. The findings are consistent with theories of pathogenic mechanisms involving vascular changes and suggest that, for males, a vascular or mixed hemodynamic profile measured during laboratory stress may be a risk marker for cardiovascular disease, by its association with ambulatory pulse pressure.


Effects of Peripheral Cooling on Upper Limb Tremor Severity and Functional Capacity in Persons with MS.
Upper limb intention tremor in persons with multiple sclerosis (pwMS) affects the ability to perform activities of daily life and is difficult to treat. The study investigated the effect of peripheral upper limb cooling on tremor severity and functional performance in MS patients with intention tremor. In experiment 1, 17 patients underwent two 15 min cooling conditions for the forearm (cold pack and cryomanchet) and one control condition. In experiment 2, 22 patients underwent whole arm cooling for 15 min using multiple cold packs. In both experiments, patients were tested at four time points (pre- and post-0, -25 and -50 min cooling) on unilateral tasks of the Test Evaluant les Membres supérieurs des Personnes Agées (TEMPA), Fahn's tremor rating scale (FTRS), Nine Hole Peg Test (NHPT). In experiment 1, the mean FTRS ranged from 13.2 to 14.1 across conditions. A two-way ANOVA showed mainly time effects, showing that cooling the forearm significantly reduced the FTRS, the performance on the NHPT, and three out of four items of the TEMPA, mostly independent of the cooling modality. In experiment 2, the mean FTRS was 13.1. A repeated measures ANOVA showed that cooling the whole arm reduced the FTRS and time needed to execute two out of four items of the TEMPA. These effects occurred immediately after cooling lasting at least 25 min. Cooling the whole upper limb led to a clinically noticeable effect on tremor severity and improved functional performance, which was pronounced during the first half-hour after cooling.


The germinal vesicle nucleus of Xenopus laevis oocytes as a selective storage receptacle for proteins.
The amorphous nucleoplasm of the germinal vesicle nucleus of Xenopus laevis oocytes has been selectively extracted under conditions which leave the nuclear formed elements morphologically intact. The nucleoplasm contains about 97% of the total nuclear proteins and on SDS-polyacrylamide gels some 68 polypeptides can be distinguished. On the basis of solubility differences, the nucleoplasmic proteins can be classified into two categories. The first consists of soluble or easily solubilized proteins which comprise about 34 polypeptides making up 87% of the nucleoplasm. A few of these proteins show electrophoretic mobilities similar to those of soluble proteins of the cytoplasm, but most are unique to the nucleus. The residual 13% of the nucleoplasmic proteins are tightly bound to a nucleoplasmic gel and can be extracted only by solubilizing the gel. The solubility characteristics of the proteinaceous gel suggest a complex held together by salt, nonpolar, hydrogen, and possibly disulfide bonding. Some 34 polypeptides can be distinguished in this gel fraction, including prominent and highly enriched polypeptides of about 115,000 and 46,000 daltons. The relatively soluble fraction of the nucleoplasm does not contain informofers and contains little or no nucleic acid. Evidence is presented that if histones are present in the germinal vesicle, they can comprise no more than about 8% of the total protein. The possibility is discussed that the unique polypeptides of the nucleoplasm may be sequestered there by selective adsorption to or in the nuclear gel.


Comparative antigenicity and immunogenicity of hepadnavirus core proteins.
The hepatitis B virus core protein (HBcAg) is a uniquely immunogenic particulate antigen and as such has been used as a vaccine carrier platform. The use of other hepadnavirus core proteins as vaccine carriers has not been explored. To determine whether the rodent hepadnavirus core proteins derived from the woodchuck (WHcAg), ground squirrel (GScAg), and arctic squirrel (AScAg) viruses possess immunogen characteristics similar to those of HBcAg, comparative antigenicity and immunogenicity studies were performed. The results indicate that (i) the rodent core proteins are equal in immunogenicity to or more immunogenic than HBcAg at the B-cell and T-cell levels; (ii) major histocompatibility complex (MHC) genes influence the immune response to the rodent core proteins (however, nonresponder haplotypes were not identified); (iii) WHcAg can behave as a T-cell-independent antigen in athymic mice; (iv) the rodent core proteins are not significantly cross-reactive with the HBcAg at the antibody level (however, the nonparticulate "eAgs" do appear to be cross-reactive); (v) the rodent core proteins are only partially cross-reactive with HBcAg at the CD4+ T-cell level, depending on MHC haplotype; and (vi) the rodent core proteins are competent to function as vaccine carrier platforms for heterologous, B-cell epitopes. These results have implications for the selection of an optimal hepadnavirus core protein for vaccine design, especially in view of the "preexisting" immunity problem that is inherent in the use of HBcAg for human vaccine development.


Modality-Specificity of the Neural Correlates of Linguistic and Non-Linguistic Demand.
Imaging studies of language processing in clinical populations can be complicated to interpret for several reasons, one being the difficulty of matching the effortfulness of processing across individuals or tasks. To better understand how effortful linguistic processing is reflected in functional activity, we investigated the neural correlates of task difficulty in linguistic and non-linguistic contexts in the auditory modality and then compared our findings to a recent analogous experiment in the visual modality in a different cohort. Nineteen neurologically normal individuals were scanned with fMRI as they performed a linguistic task (semantic matching) and a non-linguistic task (melodic matching), each with two levels of difficulty. We found that left hemisphere frontal and temporal language regions, as well as the right inferior frontal gyrus, were modulated by linguistic demand and not by non-linguistic demand. This was broadly similar to what was previously observed in the visual modality. In contrast, the multiple demand (MD) network, a set of brain regions thought to support cognitive flexibility in many contexts, was modulated neither by linguistic demand nor by non-linguistic demand in the auditory modality. This finding was in striking contradistinction to what was previously observed in the visual modality, where the MD network was robustly modulated by both linguistic and non-linguistic demand. Our findings suggest that while the language network is modulated by linguistic demand irrespective of modality, modulation of the MD network by linguistic demand is not inherent to linguistic processing, but rather depends on specific task factors.


Role of Arthroscopy in the Treatment of Osteoarthritis of Knee.
A variety of procedures have been described for treatment of the osteoarthritic knee. Comprehensive Arthroscopic treatment regime has definite role in treating patients with knee Osteoarthritis. To evaluate the role of arthroscopy in functional and subjective outcomes of patient with moderate to severe osteoarthritis of knee. Between October 2011 to September 2013, 30 patients were treated with an arthroscopic regimen. Patients with primary osteoarthritis who fulfilled clinical and radiographic classification criteria of American College of Rheumatology for osteoarthritis were included. All patients were followed for 18 months. All patients were subjected to comprehensive arthroscopic treatment. Overall, mean age was 59 years, with 17 females and 13 males. According to Kellgren Lawrence scale, 17 patients had grade 2 osteoarthritis, 10 had grade 3 osteoarthritis and 3 patients had grade 4. The average preoperative Lysholm score was 38.8. According to Outerbridge grading of chondral surface lesions, 14 patients were in grade-1, 5 in grade-2, 8 in grade-3 and 3 patients were in grade-4. The average 18 months postoperative Lysholm score was 83.3 (range 60- 96). 73.33% patients showed good/ excellent outcome. 80% of patients with chondral and meniscal lesions showed excellent/good outcome. This arthroscopic treatment regimen can improve function and activity levels in patients with moderate to severe osteoarthritis. Patients with meniscal and chondral pathology will be benefited more by arthroscopic treatment.


Research of usability of tree leaves and soil in determining the contribution of industry and traffic to air pollution in Bozüyük (Turkey) region.
In industrialized regions like Bozüyük, generally density of settlement and traffic is also observed. As a result of this density, the metal pollution that results from either industrial activities or traffic shall affect the air quality negatively. In determining this effect and sources thereof inspection of the depositing of heavy metals, which cause pollution, on the tree leaves and in the soil, and making comments by comparing with the values in the same kinds of plants and soil in the clean region has been aimed. For this purpose, zinc, copper, chromium, cadmium, iron, nickel, lead analysis have been carried out in order to determine the accumulation of pollution in plants and soils resulting from heavy industry and vehicles around Bozüyük (Turkey) region which is close to highway. These analyses have been carried out on washed and unwashed tree leave samples and surface soil from ten locations. Data used in the results were the average values of a series of data obtained from the experimental studies.


Hypoglycemic effect of subcutaneously injected biosynthetic human proinsulin in healthy man.
The effects of equipotent subcutaneously injected amounts of biosynthetic human proinsulin and biosynthetic human NPH insulin on blood glucose levels were compared in healthy male volunteers. Mean blood glucose levels decreased to approximately 50 mg/dl after injection of NPH insulin and to 46 mg/dl after injection of proinsulin. This difference reached statistical significance only between 200 and 310 min. after injection. Blood glucose levels rose only marginally thereafter, but increased promptly after ingestion of the standard meal. No differences were observed between the groups. The serum insulin levels reflected the known time insulin curves after NPH injection. The maximum of the proinsulin levels occurred about 4 hours after the injection. Subcutaneous injection of equipotent amounts of biosynthetic human proinsulin and biosynthetic human insulin have similar effects on blood glucose levels.


Cyclobenzaprine in the treatment of acute muscle spasm: review of a decade of clinical experience.
Cyclobenzaprine hydrochloride became available for the treatment of acute skeletal muscle spasm ten years ago. The initial clinical trials conducted during the premarketing evaluation of this drug showed that it was significantly superior to placebo in relieving the signs and symptoms of acute skeletal muscle spasm. In addition, cyclobenzaprine was found to have a more rapid onset of action than diazepam. Data obtained both in controlled clinical investigations and in a postmarketing surveillance program indicated that cyclobenzaprine treatment was associated with few serious adverse experiences. Cyclobenzaprine represents a cost-effective approach to the management of acute muscle spasm, primarily because of the rapid symptomatic relief that it provides.


Quenching of superoxide ions by curcumin. A mechanistic study in acetonitrile.
The quenching of superoxide ions, O2.-, by curcumin has been studied by electrogenerating this anion radical from oxygen dissolved in acetonitrile solvent (that is, at best, a mimic of the lipofilic layer of biological membranes), containing known amounts of curcumin. Voltammetric tests, combined with coulometric and spectrophotometric measurements, pointed out that each mol of curcumin is able to react with six mols of such anion radical, through a process initiated by an acid-base step, which provides the perhydroxyl radical, HO2.; that disproportionates rapidly to the anionic form of hydrogen peroxide, HO2-, and oxygen, which is thus partially regenerated. At the same time, curcumin is converted to the corresponding three-charged anion. The strict resemblance existing between the mechanism of the rapid superoxide radical decay caused by curcumin and that involved in the presence of the superoxodismutase enzyme (SOD) is also underlined.


Association between an Antioxidant-Rich Japanese Diet and Chronic Kidney Disease: The Ohasama Study.
Although physiological effects of hydrophilic- (H-) and lipophilic- (L-) antioxidant capacities (AOCs) are suggested to differ, the association of an antioxidant-rich diet and chronic kidney disease (CKD) incidence has not been examined. We therefore explored the association between the H- or L-AOC of a whole Japanese diet and CKD risk in a general population. A total of 922 individuals without CKD (69.2% women; mean age, 59.5 years old) from Ohasama Town, Japan, were examined. CKD incidence was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m 2 . Consumption of H-/L-AOC was determined based on the oxygen radical absorbance capacity in a specially developed Japanese food AOC database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for new-onset CKD using a Cox proportional hazards model. During the median follow-up of 9.7 years, 137 CKD incidents were recorded. After adjusting for potential confounding variables, the highest quartile of L-AOC was significantly associated with a 51% reduced CKD risk among only women. An increased L-AOC intake was more effective in preventing eGFR reduction than in preventing proteinuria in women. These associations were not seen for H-AOC intake in both sexes and L-AOC intake in men. A high intake of lipophilic antioxidants may be associated with a reduced CKD risk. The balance between dietary antioxidant intake and pro-oxidants induced by unhealthy lifestyles may be crucial for preventing future kidney deterioration.


Attitudes of psychiatrists toward antipsychotic depot medication.
Since 2002, a second-generation depot antipsychotic has been available that potentially combines the advantages of depot administration and the favorable aspects of the so-called "atypical" antipsychotics. Nevertheless, long-acting injectable formulations are seldom prescribed in the treatment of schizophrenia. We surveyed 350 psychiatrists at an international conference as to their reasons for not prescribing a first- or second-generation depot antipsychotic for their patients diagnosed with schizophrenia or schizoaffective disorder. The most important factor opposing depot prescription pertaining to both classes is a presumed sufficient compliance with oral antipsychotic treatment. First-generation depots are avoided due to the threat of extrapyramidal side effects, whereas second-generation long-acting injectable drugs are considered to be associated with high treatment costs. Less than 36% of participants' patients have ever been offered antipsychotic depot treatment. Aversions to prescribing depot treatment are frequent among psychiatrists and appear to be unrelated to the antipsychotic class. The stated reasons for not prescribing depots are generally not supported by the current evidence, and further studies are urgently needed to clarify the advantages of depot treatment.


Congenital bilateral anterior nasal atresia in 16 half-sibling Holstein-Friesian calves.
Cases of bilateral anterior nasal atresia, sometimes referred to as arhinia or partial arhinia, are extremely rare in cattle and have only been reported as single events. This report describes the birth of 16 Holstein Friesian calves over a 3-month period, all affected with bilateral atresia of the nares and anterior nasal cavity, with 2 calves having additional severe deviation of the nasomaxillary bones and nasal septum. One affected calf was born with an anatomically normal twin. Parentage testing demonstrated that a single Holstein Friesian bull sired all cases tested. This is the first report of multiple cases of bilateral anterior nasal atresia in cattle with evidence that demonstrates a heritable condition.


Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival after Unmanipulated Haploidentical Blood and Marrow Transplantation.
Rapid immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is significantly associated with lower infection, relapse and possibly secondary malignancy rates. The aim of this study was to investigate the role of peripheral lymphocyte subsets, especially CD3+CD8+ cytotoxic T cell recovery, in predicting transplant outcomes, including the overall survival (OS) and non-relapse mortality (NRM) rates after unmanipulated haploidentical blood and marrow transplantation (HBMT). Peripheral blood samples were obtained from 214 HBMT recipients with hematological malignancies. The peripheral lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, and CD19+ B cells) were analyzed by flow cytometry at days 30, 60, 90, 180, 270 and 360 after HBMT. The CD3+CD8+ cytotoxic T cell recovery at day 90 (CD3+CD8+-90) was correlated with bacterial infection (P = 0.001), NRM (P = 0.001), leukemia-free survival (LFS, P = 0.005), and OS (P = 0.001) at a cutoff value of 375 cells/μL CD3+CD8+ T cells. The incidence of bacterial infection in patients with the CD3+CD8+-90 at ≥375 cells/μL was significantly lower than that of cases with the CD3+CD8+-90 at <375 cells/μL after HBMT (14.6% versus 41.6%, P<0.001). Multivariate analysis showed the rapid recovery of CD3+CD8+ T cells at day 90 after HBMT was strongly associated with a lower incidence of NRM (HR = 0.30; 95% CI: 0.15-0.60; P = 0.000) and superior LFS (HR = 0.51; 95% CI: 0.32-0.82; P = 0.005) and OS (HR = 0.38; 95% CI: 0.23-0.63; P = 0.000). The results suggest that the rapid recovery of CD3+CD8+ cytotoxic T cells at day 90 following HBMT could predict superior transplant outcomes.


Non-enzymatic molecular damage as a prototypic driver of aging.
The chemical potentialities of metabolites far exceed metabolic requirements. The required potentialities are realized mostly through enzymatic catalysis. The rest are realized spontaneously through organic reactions that (i) occur wherever appropriate reactants come together, (ii) are so typical that many have proper names (e.g. Michael addition, Amadori rearrangement, and Pictet-Spengler reaction), and (iii) often have damaging consequences. There are many more causes of non-enzymatic damage to metabolites than reactive oxygen species and free radical processes (the "usual suspects"). Endogenous damage accumulation in non-renewable macromolecules and spontaneously polymerized material is sufficient to account for aging and differentiates aging from wear-and-tear of inanimate objects by deriving it from metabolism, the essential attribute of life.


Microarray expression profiling of Yersinia pestis in response to berberine.
Coptis chinensis Franch. is a natural herb widely used in China for prevention and treatment of infectious diseases. Plague is a deadly disease caused by Yersinia pestis. Coptis chinensis Franch. is considered the therapeutic agent of choice against plague rather than conventional antibiotics because of its low cost and low toxicity. Berberine is the major constituent of a Coptis chinensis Franch. extract. In the present study, DNA microarray was used to investigate the transcription of Y. pestis in response to berberine. The minimal inhibition concentration (MIC) of berberine to Y. pestis was determined with the liquid dilution method. The gene expression profile of Y. pestis was performed by exposing Y. pestis to berberine at a concentration of 10 x MIC for 30 min. Total RNA was extracted and purified from Y. pestis, reverse-transcribed to cDNA, and then labeled with Cy-dye probes. The labeled probes were hybridized to the microarray. The results were obtained by a laser scanner and analyzed with SAM software. A total of 360 genes were differentially expressed in response to berberine: 333 genes were upregulated, and 27 were downregulated. The upregulation of genes that encode proteins involved in metabolism was a remarkable change. In addition to a number of genes of unknown encoding or unassigned functions, genes encoding cellular envelope and transport/binding functions represented the majority of the altered genes. A number of genes related to iron uptake were induced. This study revealed global transcriptional changes of Y. pestis in response to berberine, hence providing insights into the mechanisms of Coptis chinensis Franch. against Y. pestis.


Simulation, power evaluation and sample size recommendation for single-cell RNA-seq.
Determining the sample size for adequate power to detect statistical significance is a crucial step at the design stage for high-throughput experiments. Even though a number of methods and tools are available for sample size calculation for microarray and RNA-seq in the context of differential expression (DE), this topic in the field of single-cell RNA sequencing is understudied. Moreover, the unique data characteristics present in scRNA-seq such as sparsity and heterogeneity increase the challenge. We propose POWSC, a simulation-based method, to provide power evaluation and sample size recommendation for single-cell RNA-sequencing DE analysis. POWSC consists of a data simulator that creates realistic expression data, and a power assessor that provides a comprehensive evaluation and visualization of the power and sample size relationship. The data simulator in POWSC outperforms two other state-of-art simulators in capturing key characteristics of real datasets. The power assessor in POWSC provides a variety of power evaluations including stratified and marginal power analyses for DEs characterized by two forms (phase transition or magnitude tuning), under different comparison scenarios. In addition, POWSC offers information for optimizing the tradeoffs between sample size and sequencing depth with the same total reads. POWSC is an open-source R package available online at https://github.com/suke18/POWSC. Supplementary data are available at Bioinformatics online.


Exogenous female sex steroid hormones and new-onset asthma in women: a matched case-control study.
Evidence on the role of exogenous female sex steroid hormones in asthma development in women remains conflicting. We sought to quantify the potential causal role of hormonal contraceptives and menopausal hormone therapy (MHT) in the development of asthma in women. We conducted a matched case-control study based on the West Sweden Asthma Study, nested in a representative cohort of 15,003 women aged 16-75 years, with 8-year follow-up (2008-2016). Data were analyzed using Frequentist and Bayesian conditional logistic regression models. We included 114 cases and 717 controls. In Frequentist analysis, the odds ratio (OR) for new-onset asthma with ever use of hormonal contraceptives was 2.13 (95% confidence interval [CI] 1.03-4.38). Subgroup analyses showed that the OR increased consistently with older baseline age. The OR for new-onset asthma with ever MHT use among menopausal women was 1.17 (95% CI 0.49-2.82). In Bayesian analysis, the ORs for ever use of hormonal contraceptives and MHT were, respectively, 1.11 (95% posterior interval [PI] 0.79-1.55) and 1.18 (95% PI 0.92-1.52). The respective probability of each OR being larger than 1 was 72.3% and 90.6%. Although use of hormonal contraceptives was associated with an increased risk of asthma, this may be explained by selection of women by baseline asthma status, given the upward trend in the effect estimate with older age. This indicates that use of hormonal contraceptives may in fact decrease asthma risk in women. Use of MHT may increase asthma risk in menopausal women.


Genetically modified animals: ethical issues.
The method of ethical analysis is reviewed and applied to questions relating to the unintended consequences, ownership, and metaphysical significance of genetically modified animals. The question of how genetics and recombinant DNA discoveries have an impact on human understanding of the moral community and the limits of acceptable action are emphasized. The potential for genetically modified animals presents a challenge to implicit norms for defining these boundaries. Four philosophical responses to this challenge are reviewed: fundamentalism, conventionalism, dualism, and naturalism. The naturalist response is most consistent with contemporary biology, but it also entails that animals have limited moral significance.


Methamphetamine-withdrawal stress activates PACAP-DBI pathway in rat salivary gland, resulting in inhibition of salivary secretion.
The purpose of this study was to investigate activation of inhibitory regulation pathways by methamphetamine (METH)-withdrawal stress in rat salivary gland. Our previous study showed that METH-withdrawal stress activated steroid biosynthesis and that pregnenolone produced during the early stage of this process inhibited salivary secretion. However, how this type of stress inhibits salivary secretion and the activation pathway of steroid biosynthesis in salivary gland remain to be clarified. In the present study, using an in vivo cannulation method, METH-withdrawal stress decreased salivary secretion and increased expression of diazepam-binding inhibitor (DBI), an endogenous peripheral-type benzodiazepine receptor (PBR) agonist; Western blot and RT-PCR also showed increased expression of DBI mRNA in parotid, submandibular, and sublingual gland. In addition, METH-withdrawal stress also elicited an increase in pituitary adenylate cyclase-activating polypeptide (PACAP) and PBR mRNA, which is associated with DBI activity. These results suggest that METH-withdrawal stress activates a PACAP-DBI pathway in salivary gland, enhancing steroid genesis and inhibiting secretion.


Augmented Reality for Real-Time Detection and Interpretation of Colorimetric Signals Generated by Paper-Based Biosensors.
Colorimetric tests are becoming increasingly popular in point-of-need analyses due to the possibility of detecting the signal with the naked eye, which eliminates the utilization of bulky and costly instruments only available in laboratories. However, colorimetric tests may be interpreted incorrectly by nonspecialists due to disparities in color perception or a lack of training. Here we solve this issue with a method that not only detects colorimetric signals but also interprets them so that the test outcome is understandable for anyone. It consists of an augmented reality (AR) app that uses a camera to detect the colored signals generated by a nanoparticle-based immunoassay, and that yields a warning symbol or message when the concentration of analyte is higher than a certain threshold. The proposed method detected the model analyte mouse IgG with a limit of detection of 0.3 μg mL-1, which was comparable to the limit of detection afforded by classical densitometry performed with a nonportable device. When adapted to the detection of E. coli, the app always yielded a "hazard" warning symbol when the concentration of E. coli in the sample was above the infective dose (106 cfu mL-1 or higher). The proposed method could help nonspecialists make a decision about drinking from a potentially contaminated water source by yielding an unambiguous message that is easily understood by anyone. The widespread availability of smartphones along with the inexpensive paper test that requires no enzymes to generate the signal makes the proposed assay promising for analyses in remote locations and developing countries.


Experimenting with modifications to consent forms in comparative effectiveness research: understanding the impact of language about financial implications and key information.
Informed consent forms are intended to facilitate research enrollment decisions. However, the technical language in institutional templates can be unfamiliar and confusing for decision-makers. Standardized language describing financial implications of participation, namely compensation for injury and costs of care associated with participating, can be complex and could be a deterrent for potential participants. This standardized language may also be misleading in the context of comparative effectiveness trials of standard care interventions, in which costs and risk of injury associated with participating may not differ from regular medical care. In addition, the revised U.S. Common Rule contains a new requirement to present key information upfront; the impact of how this requirement is operationalized on comprehension and likelihood of enrollment for a given study is unknown. Two online surveys assessed the impact of (1) changes to compensation for injury language (standard vs. tailored language form) and (2) changes to the key information page (using the tailored compensation language form with standard key information vs. modified key information vs. modified key information plus financial information) on both likelihood of enrollment in and understanding of a hypothetical comparative effectiveness trial. Likelihood of enrolling was not observed to be different between the standard and tailored language forms in Study 1 (73 vs. 75%; p = 0.6); however, the tailored language group had a higher frequency of understanding the compensation for injury process specific to the trial (25 vs. 51%; p < 0.0001). Modifications to the key information sheet in Study 2 did not affect likelihood of enrolling (88 vs. 85 vs. 85%; p = 0.6); however, understanding of randomization differed by form (44 vs. 59 vs. 46%; p = 0.002). These findings suggest that refining consent forms to clarify key information and tailoring compensation for injury language to the nature of the study, especially in the context of comparative effectiveness trials, may help to improve study comprehension but may not impact enrollment.


bis-Molybdopterin guanine dinucleotide is required for persistence of Mycobacterium tuberculosis in guinea pigs.
Mycobacterium tuberculosis is able to synthesize molybdopterin cofactor (MoCo), which is utilized by numerous enzymes that catalyze redox reactions in carbon, nitrogen, and sulfur metabolism. In bacteria, MoCo is further modified through the activity of a guanylyltransferase, MobA, which converts MoCo to bis-molybdopterin guanine dinucleotide (bis-MGD), a form of the cofactor that is required by the dimethylsulfoxide (DMSO) reductase family of enzymes, which includes the nitrate reductase NarGHI. In this study, the functionality of the mobA homolog in M. tuberculosis was confirmed by demonstrating the loss of assimilatory and respiratory nitrate reductase activity in a mobA deletion mutant. This mutant displayed no survival defects in human monocytes or mouse lungs but failed to persist in the lungs of guinea pigs. These results implicate one or more bis-MGD-dependent enzymes in the persistence of M. tuberculosis in guinea pig lungs and underscore the applicability of this animal model for assessing the role of molybdoenzymes in this pathogen.


Cutaneous Anaplastic Large Cell Lymphoma: A Case Report about Masking Effect of Facial Masks in the COVID-19 Pandemic.
The COVID-19 global pandemic commenced widespread usage of face masks. Due to covering of the lower face in public settings, limited social interaction, and patient hesitancy for seeking in-person healthcare, dermatologic conditions of the lower face are prone to delayed diagnosis and management. With society recovering from the pandemic and social distancing restrictions being lifted, an increasing number of patients present with malignant skin conditions at advanced stage. The authors describe a 47-year-old female patient who presented with a 4-month-old facial mass that was initially believed to originate from skin irritation caused by mask-wearing. A biopsy revealed primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This case report outlines the management of the rare PC-ALCL lesion and diagnostic challenges related to facial masks and social distancing.


A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes.
Cisplatin is an effective agent for triple-negative breast cancer (TNBC) and synergistic activity between cisplatin and capecitabine has been demonstrated by in vitro and in vivo studies. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of capecitabine plus cisplatin (XP) regimen in metastatic TNBC patients pretreated with anthracyclines and taxanes. Thirty-three patients with metastatic TNBC who had anthracyclines and taxanes as prior therapy were treated with capecitabine 2000 mg/m(2) orally on day 1 through 14 plus cisplatin 75 mg/m(2) intravenously on day 1 of a 21-day cycle, followed by capecitabine maintenance medications after a maximum of 6 cycles. The primary end point was objective response rate (ORR) and the secondary end points included progression-free survival (PFS), overall survival (OS) and toxicity profiles. A total of 162 cycles was given. ORR was 63.6%. Median PFS was 8.2 (95%CI: 4.8-11.6) months in the entire population and 10.8 (95%CI: 6.5-15.1) months in responding patients. Median OS was 17.8 (95%CI: 14.4-21.2) months in all enrolled patients and 25.8 (95%CI: 14.6-37.0) months in responding patients. Most adverse events were mild and manageable, with neutropenia and nausea/vomiting as the most common toxicities. Grade 3/4 toxicities included leukopenia (10, 30.3%), neutropenia (10, 30.3%), anemia (2, 6.1%), thrombocytopenia (1, 3.0%), nausea/vomiting (3, 9.1%), hand-foot syndrome (HFS; 1, 3.0%), and sensory neuropathy (1, 3.0%). Capecitabine plus cisplatin demonstrated an excellent activity and an acceptable safety profile in metastatic TNBC patients pretreated with anthracyclines and taxanes.


Function of iron-stress-induced protein A in cyanobacterial cells with monomeric and trimeric Photosystem I.
The acclimation of cyanobacteria to iron deficiency is crucial for their survival in natural environments. In response to iron deficiency, many cyanobacterial species induce the production of a pigment-protein complex called IsiA (iron-stress-induced protein A). IsiA proteins associate with photosystem I (PSI) and can function as light-harvesting antennas or dissipate excess energy. They may also serve as chlorophyll storage during iron limitation. In this study, we examined the functional role of IsiA in cells of Synechocystis sp. PCC 6803 grown under iron limitation conditions by measuring the cellular IsiA content and its capability to transfer energy to PSI. We specifically tested the effect of the oligomeric state of PSI by comparing wild-type (WT) Synechocystis sp. PCC 6803 to mutants lacking specific subunits of PSI, namely PsaL/PsaI (PSI subunits XI/VIII) and PsaF/PsaJ (PSI subunits III/IX). Time-resolved fluorescence spectroscopy revealed that IsiA formed functional PSI3-IsiA18 supercomplexes, wherein IsiA effectively transfers energy to PSI on a timescale of 10 ps at room temperature - measured in isolated complexes and in vivo - confirming the primary role of IsiA as an accessory light-harvesting antenna to PSI. However, a notable fraction (40%) remained unconnected to PSI, supporting the notion of a dual functional role of IsiA. Cells with monomeric PSI under iron deficiency contained, on average, only 3-4 IsiA complexes bound to PSI. These results show that IsiA can transfer energy to trimeric and monomeric PSI but to varying degrees and that the acclimatory production of IsiA under iron stress is controlled by its ability to perform its light-harvesting function.


Genetic variants in SUSD2 are associated with the risk of ischemic heart disease.
Genetic factors partly determine the risk for premature myocardial infarction (MI). We report the identification of a novel rare genetic variant in a kindred with an autosomal dominant trait for premature MI and atherosclerosis and explored the association of a common nonsynonymous variant in the same gene with the risk of ischemic heart disease (IHD) in a population-based study. Next-generation sequencing was performed in a small pedigree with premature MI or subclinical atherosclerosis. A common variant, rs8141797 A>G (p.Asn466Ser), in sushi domain-containing protein 2 (SUSD2) was studied in the prospective Copenhagen General Population Studies (N = 105,408) for association with IHD. A novel heterozygous nonsense mutation in SUSD2 (c.G583T; p.Glu195Ter) was associated with the disease phenotype in the pedigree. SUSD2 protein was expressed in aortic specimens in the subendothelial cell layer and around the vasa vasorum. Furthermore, the minor G-allele of rs8141797 was associated with per allele higher levels of SUSD2 mRNA expression in the heart and vasculature. In the Copenhagen General Population Study, hazard ratios for IHD were 0.92 (95% CI: 0.87-0.97) in AG heterozygotes and 0.86 (0.62-1.19) in GG homozygotes vs noncarrriers (P-trend = .002). Finally, in meta-analysis including 73,983 IHD cases and 215,730 controls, the odds ratio for IHD per G-allele vs A-allele was 0.93 (0.90-0.96) (P = 4.6 × 10-7). The identification of a truncating mutation in SUSD2, which was associated with premature MI and subclinical atherosclerosis, combined with the finding that a common missense variant in SUSD2 was strongly associated with a lower risk of IHD, suggest that SUSD2 may alter the risk of atherosclerosis.


Experience with 112 shotgun wounds of the extremities.
Although shotgun and gunshot injuries are frequently grouped together, shotgun injuries are ballistically and clinically very different from gunshot wounds. Because of the differences between gunshot and shotgun injuries, the clinical records of 85 patients with 112 extremity shotgun wounds treated over a 6-year period were reviewed: 11% had Type I injuries; 30% and 59%, respectively, had Type II and Type III injuries. Overall, 59% had major soft-tissue injuries and 44% had bone or joint injuries, and nerve and vascular injuries were documented in 21% and 26%. The major cause of a prolonged hospital stay was the presence of a major soft-tissue injury, while the presence or absence of a neural injury was the most important determinate of whether the extremity would be functional. In contrast, neither skeletal nor vascular injuries resulted in long-term extremity disability. Thus, we recommend an aggressive operative approach towards early wound closure in these patients to decrease hospitalization time. Further, we believe that the operative determination of the presence or absence of anatomic damage of the nerves in patients with neural deficits is an important component in the long-term management of these patients.