Role of transient receptor potential channels in intestinal inflammation and visceral pain: novel targets in inflammatory bowel diseases.
Transient receptor potential (TRP) channels are a large group of ion channels that are prevalent in mammalian tissues. They are widely distributed in the central and peripheral nervous systems, and in nonneuronal cells, where they are implicated in sensing temperature, noxious substances, and pain. TRPs play an important role in immune response and nociception and, therefore, may be involved in the pathogenesis of inflammatory bowel diseases, whose major symptoms include chronic inflammatory state and abdominal pain. In this review, we summarize what is known on TRP channels in inflammatory bowel disease and visceral pain; we focus in particular on TRPV1, TRPV4, TRPA1, and TRPM. We also analyze scientific reports that evidence potential use of TRP regulators in future inflammatory bowel disease treatment.


Knockdown of mineralocorticoid or angiotensin II type 1 receptor gene expression in the paraventricular nucleus prevents angiotensin II hypertension in rats.
Circulating Ang II activates an aldosterone-mineralocorticoid receptor (MR) - angiotensin II (Ang II) - angiotensin type 1 receptor (AT1R) pathway in the hypothalamus. To obtain insights into the actual neuronal projections involved, adeno-associated virus carrying small interfering RNA against either AT1aR (AAV-AT1aR-siRNA) or MR (AAV-MR-siRNA) were infused into the paraventricular nucleus (PVN) in Wistar rats. Intra-PVN infusion of AAV-AT1aR-siRNA or AAV-MR-siRNA decreased AT1R or MR expression in the PVN but not in the subfornical organ (SFO) or supraoptic nucleus (SON). Subcutaneous infusion of Ang II at 500 ng kg(-1) min(-1) for 2 weeks increased mean arterial pressure by 60-70 mmHg, and increased AT1R and MR expression in the SFO, SON and PVN. Intra-PVN AT1aR-siRNA prevented the Ang II-induced increase in AT1R but not MR expression in the PVN, and MR-siRNA prevented MR but not AT1R expression in the PVN. The increases in AT1R and MR expression in both the SFO and the SON were not changed by the two AAV-siRNAs. Specific knockdown of AT1R or MR in the PVN by AAV-siRNA each prevented most of the Ang II-induced hypertension. Prevention of the subcutaneous Ang II-induced increase in MR but not the increase in AT1R by knockdown of MR and vice versa suggests an independent regulation of MR and AT1R expression in the PVN. Both AT1R and MR activation in the PVN play a critical role in Ang II-induced hypertension in rats.


[Bone metabolism and cardiovascular function update. Estrogen and its therapeutic potential for bone and vascular health].
Despite its long-standing role as a "guardian angel" for the female body, estrogen has recently been dethroned from its status as an "elixir" and its use has been restricted due to its oncogenic potential as well as its coagulation system-associated risk. However, it is recognized that estrogen not only works against bone resorption but also improves vascular function. In this regard, it is suggested that estrogen may have a role in improving deteriorated bone quality through its antioxidant action, while this same effect with the SERMs, which may be accounted for by the presence of estrogen, remains yet to be established. Not only evidence needs to be accumulated to support the vascular effects of the SERMs, but their pleiotropic, rather than extra-skeletal, effects, as likely mediated by the estrogen receptors distributed throughout the body, remain to be elucidated.


Delayed hypersensitivity responses in mice and guinea pigs to Mycobacterium leprae, Mycobacterium vaccae, and Mycobacterium nonchromogenicum cytoplasmic proteins.
Antigenic relationships between Mycobacterium vaccae, M. nonchromogenicum, and M. leprae were examined in mice and guinea pigs injected with M. vaccae or M. nonchromogenicum suspensions. The growth of both organisms in outbred ICR and four inbred mouse strains was followed up to 30 days. M. nonchromogenicum persisted in the livers and spleens of the inbred mice substantially better than did the M. vaccae population in the same mouse strains. A translucent colony variant of M. vaccae isolated from the opossum survived in vivo better than the opaque colony isolated from opossums and cattle. Persistence of M. vaccae and M. nonchromogenicum was not markedly increased in T-cell-depleted (nude) mice. Normal mice infected with increasing numbers of M. vaccae did not develop delayed-type hypersensitivity to the homologous M. vaccae cytoplasmic protein antigen. When heat-killed M. vaccae were incorporated into Freund adjuvant, both mice and guinea pigs developed delayed hypersensitivity to cytoplasmic antigens prepared from M. vaccae, M. nonchromogenicum and M. vaccae vaccines cross-sensitized guinea pigs to the M. leprae cytoplasmic antigens.


[Indication, techniques and results of the operative correction of hypospadias using modification of the original Denis Browne technique (author's transl)].
The experiences with operative correction of hypospadias 416 patients are reported. In 264 of these patients the correction of the hypospadic deformity was completed, using the original Denis Browne technique or a modification described by Marberger. The results and the complications are demonstrated.


Metrizamide-phenothiazine interaction. Report of a case with seizures following myelography.
One single clinical complication of grand mal seizures in conjunction with the subarachnoid administration of the new non-ionic contrast medium metrizamide is reported in a patient who had been taking chlorpromazine. An interaction between the contrast medium and phenothiazine derivatives is considered probable.


Low Dose Iron Therapy in Children with Iron Deficiency: DNA Damage and Oxidant Stress Markers.
Conflicting data are available regarding oral iron therapy in iron deficiency (ID), iron deficiency anemia (IDA) and its relation to DNA damage, oxidative stress and antioxidant markers. Our aim was assessment of DNA damage, oxidative stress and anti-oxidant markers in children with ID and IDA before and after low dose iron therapy. The study was conducted in two stages, first stage was assessment of DNA damage using comet assay, malondialdehyde (MDA) and anti-oxidant enzymes levels (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) & total antioxidant capacity (TAC) in thirty-nine children with IDA, forty-five children with ID without anemia and sixty healthy controls. Second stage was assessment of previous markers together with hematological response following oral therapy with 10 mg/day ferric ammonium citrate for 8 weeks. Before treatment, there was no significant difference between the three groups regarding MDA, GPx, SOD, CAT and TAC. A significant increase was detected in the DNA damage in the 2 groups compared to control (p < 0.005). Following iron therapy, hematological parameters was improved together with a significant increase in GPx (P = 0.04), SOD (p = 0.002), TAC (P = 0.001) and non-significant reduction in DNA damage in IDA group. There was a significant increase in SOD (p = 0.001) & TAC (p = 0.001) and significant decrease in DNA damage (p = 0.001) in ID group. Low dose iron therapy could be sufficient to improve antioxidant status and DNA damage together with correction of hematologic indices.


Selected aspects of deconditioning secondary to immobilization.
Although activity is a normal state of the human body, a variety of orthopedic conditions may necessitate some degree of immobilization. Major deconditioning changes in the cardiovascular system and musculoskeletal system have been identified. The deconditioning changes affecting the cardiovascular system are decreased venous flow, decreased orthostatic tolerance, and decreased work capacity. The deconditioning changes associated with the musculoskeletal system are bone demineralization, altered joint function, and loss of muscle mass, strength, and tone. Possible nursing interventions and their rationales for use with the identified deconditioning changes have been explored. The general goal of any intervention is to minimize the deconditioning that occurs with immobilization.


CT and MRI findings of type I and type II epithelial ovarian cancer.
To assess whether types I and II epithelial ovarian cancer (EOC) differ in CT and MRI imaging features. For this retrospective study, we enrolled 65 patients with 68 ovarian lesions that have been pathologically proven to be EOC. Of these patients, 38 cases underwent MR examinations only, 15 cases underwent CT examinations only, and 12 cases completed both examinations. The clinical information [age, CA-125, menopausal status, and Ki-67] and imaging findings were compared between two types of EOCs. The diagnostic performance of image findings were assessed by receiver-operating characteristic curve(ROC) analysis. The association between EOC type and imaging features was assessed by multivariate logistic regression analysis. The random forest approach was used to build a classifier in differential diagnosis between two types of EOCs. Of the 68 EOC lesions, 24 lesions were categorized as types I and other 44 lesions as type II based on the immunohistochemical results, respectively. Patients in type I EOCs were more likely to involve menopausal women and showed lower CA-125 and Ki-67 values (Ki-67<30%) than patients in type II EOCs. The imaging characteristics of type II EOCs frequently demonstrated a solid or predominantly solid mass (38.6% vs. 12.5%, P<0.05), smaller lesions (diameter <6cm; 27.3% vs. 4.2%, P<0.05), absence of mural nodules (65.9% vs. 25.9%, P=0.001), and mild enhancement (84.1% vs. 54.2%, P<0.05) compared to type I EOCs. Combination of tumor size, morphology, mural nodule, enhancement degrees (AUC=0.808) has a higher specificity (87.50%) and positive predictive value (90.0%) than any single image finding alone in differential diagnosis between two types of EOCs. The multivariate logistic regression analysis showed that enhancement degrees(OR 0.200, P<0.05),mural nodule(OR 0.158, P<0.05) significantly influence EOC classification. Random forests model identified both as the most important discriminating variables. The diagnostic accuracy of the classifier was 73.53%. Differences in imaging characteristics existed between two types of EOCs. Combination of several image findings improved the preoperative diagnostic performance, which is helpful for the clinical treatment and prognosis evaluation.


Some properties of purified skeletal muscle alpha-actinin.
Highly purified alpha-actinin can be made by using the low ionic strength extraction procedure previously described (Arakawa N., Robson, R. M., and Goll, D. E. (1970) Biochim. Biophys. Acta 200, 284-295) and then subjecting the crude alpha-actinin fraction obtained with this extraction procedure to successive chromatography on DEAE-cellulose and hydroxyapatite. Hydrozyapatite chromatography specifically removes a protein having a subunit molecular weight of 42,000 on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Hydroxyapatite-purified alpha-actinin sediments entirely as a 6.21 S boundary in the analytical ultracentrifuge with no trace of the small 9 to 10 S boundary seen in earlier alpha-actinin preparations purified by DEAE-cellulose chromatography. In 100 mM KCl, 20 mM Tris-acetate, pH 7.5, hydroxyapatite-purified alpha-actinin has a diffusion coefficient (D020,w) of 2.71 X 10(-7) cm2-s-1, an intrinsic viscosity of 20.6 ml-g-1, a molecular weight of 201,000 +/- 4,300 (plus or minus least squares standard error) as determined by sedimentation equilibrium, and a molecular weight of 210,000 as determined by sedimentation diffusion. In 6 M guanidine HCl, hydroxyapatite-purified alpha-actinin has a molecular weight of 106,000 +/- 6,300 as determined by sedimentation equilibrium and a molecular weight of 100,000 as determined by a calibrated 4% agarose gel permeation column. SDS-polyacrylamide gel electrophoresis gives a molecular weight of 96,000 to 100,000 for hydroxyapatite-purified alpha-actinin. Rod-shaped particles 44 X 390 to 400 A are seen in electron micrographs of negatively stained alpha-actinin. By assuming 45% hydration and a molecular weight of 206,000, dimensions of approximately 40 X 500 A can be calculated for the alpha-actinin molecule by using either s 020, w, D 020, w, intrinsic viscosity, or a calibrated 6% agarose gel permeation column. Hydroxyapatite-purified alpha-actinin has an alpha-helical content of 74% as measured by circular dichroism at 208 nm.


An iPSC line derived from a human acute myeloid leukemia cell line (HL-60-iPSC) retains leukemic abnormalities and displays myeloid differentiation defects.
Cancer-derived iPSCs have provided valuable insight into oncogenesis, but human cancer cells can often be difficult to reprogram, especially in cases of complex genetic abnormalities. Here we report, to our knowledge, the first successful generation of an iPSC line from a human immortalized acute myeloid leukemia (AML) cell line, the cell line HL-60. This iPSC line retains a majority of the leukemic genotype and displays defects in myeloid differentiation, thus providing a tool for modeling and studying AML.


Understanding changes in the standardized antimicrobial administration ratio for total antimicrobial use after implementation of prospective audit and feedback.
In this single-center study, the standardized antimicrobial administration ratio (SAAR) for total antimicrobial use decreased in response to a stewardship intervention. Antimicrobial prescribing and clinical outcomes were stable or improved during the period of lower SAARs. Our findings suggest that SAAR values of ~0.8 can be safely achieved.


US National Health Data on Asian Americans and Pacific Islanders: a research agenda for the 1990s.
In spite of over 30 years of periodic nationwide surveys, we have thus far only the most rudimentary estimates of the determinants of the health of Asian Americans and Pacific Islanders. This paper explores ways to improve the capability of the National Center for Health Statistics (NCHS) to collect national health data on these populations. The NCHS "race" coding practices are reviewed, their limitations stated, ways to improve the numerator and denominator data discussed, and a research agenda presented. Resources can be intensified to produce better denominator data, and to improve the collection of detailed ethnicity information for the numerators, in at least the three states (California, New York, and Hawaii) where the majority of Asian/Pacific Islanders lived in 1990. Subsequently, these efforts should be extended to the 10 states where 79% of these individuals reside or to the top 15 metropolitan areas where they are concentrated. If the recommendations are implemented, several coordinated multisite, multiwave epidemiologic surveys can be conducted using standardized interview instruments and data collection procedures that will capitalize on the geographic distribution of Asian/Pacific Islanders.


Focus groups on cardiovascular health in rural women: implications for practice.
To determine rural women's perceptions about cardiovascular disease (CVD) prevention and behavior change for cardiovascular health. A trained moderator and nutritionist (observer) led the groups. The discussion guide was developed from the Health Belief Model and Social Cognitive Theory. The data were analyzed inductively looking at patterns and themes that emerged from the data and deductively looking at relationships from the theoretical models. Thirty-four white women participated in six groups: three younger (20-40 years; n = 18) and three older (40-55 years; n = 16) groups. Women with no more than 13 years of education were recruited by social service providers, Extension agents, and church groups. Rural women were unaware of their personal CVD risks. Common themes included the overriding influence of family preferences and cultural food patterns on women's food choices and the lack of support for adoption of a heart-healthy diet. Self-efficacy for dietary change spanned the continuum from no confidence (younger women) to complete empowerment (older women). Efforts need to be directed toward providing education and skill building for CVD prevention based on a better understanding of women's cultural beliefs and life situations. All women believed that dietary choices were important for cardiovascular health; however, they lacked the skills for food selection and preparation. Family preference and support are key to the adoption and maintenance of a heart-healthy eating plan. For interventions, women preferred active learning (hands-on experiences) coupled with group classes for learning and support. Rural women lacked these resources or access to a nutritionist.


Genome Sequences of Nine Bordetella holmesii Strains Isolated in the United States.
An increasing number of pertussis-like cases are attributed to the emergent pathogen Bordetella holmesii. The genomes of 9 clinical isolates show that they are clonal, lack the virulence factors encoded by B. pertussis, and are more similar to nonpertussis bordetellae. New markers for B. holmesii can be developed using these sequences.


Long-term neurological and neuropsychological complications of sulfur mustard and Lewisite mixture poisoning in Chinese victims exposed to chemical warfare agents abandoned at the end of WWII.
In August 2003, 44 victims were poisoned by chemical warfare agents (CWAs) leaked from five drums that were excavated at a construction site in Qiqihar, Northeast China. The drums were abandoned by the former Japanese imperial army during World War II and contained a mixture of Sulfur mustard (SM) and Lewisite. We carried out a total of six regular check-ups between 2006 and 2014, and from 2008 we added neurological evaluations including neuropsychological test and autonomic nervous function test in parallel with medical follow-up as much as was possible. Severe autonomic failure, such as hyperhidrosis, pollakiuria, diarrhoea, diminished libido, and asthenia appeared in almost all victims. Polyneuropathy occurred in 35% of the victims and constricted vision occurred in 20% of them. The rates of abnormal response on cold pressor test (CPT), active standing test (AST), Heart rate variability (CVR-R), performed in 2014, were 63.1%, 31.6%, and 15.9%, respectively. On neuropsychological testing evaluated in 2010, a generalized cognitive decline was observed in 42% of the victims. Memories and visuospatial abilities were affected in the remaining victims. Finally, a 17-item PTSD questionnaire and the Beck Depression Inventory evaluated in 2014 revealed long-lasting severe PTSD symptoms and depression of the victims. Our findings suggest that an SM/Lewisite compound have significant adverse consequences directly in cognitive and emotional network and autonomic nervous systems in the brain.


Analysis of odor discrimination by multidimensional scaling at different temperatures.
Discrimination of odorants by the turtle olfactory bulb at 25 degrees and 37 degrees C was examined by the cross-adaptation technique and analysed by multidimensional scaling. Analysis by multidimensional scaling suggests that at 25 degrees C odorants are grouped according to their odor qualities in the turtle olfactory system. At 37 degrees C, the cluster formation of odorants, which have a similar odor quality,such as minty and floral alcohol odorants and molecular structure, in the plot of multidimensional scaling was poor, indicating that the ability of odor grouping according to their odor qualities was low at 37 degrees C.


3-[(E)-3-(4-Meth-oxy-phen-yl)prop-2-eno-yl]-1-(4-methyl-phen-yl)-5-phenyl-1H-pyrazole-4-carbonitrile.
In the title compound, C(27)H(21)N(3)O(2), the non-H atoms of the meth-oxy-phenyl-acryloyl substitutent of the pyrazolyl ring are almost co-planar (r.m.s. deviation = 0.070 Å), and the mean plane is twisted by 18.7 (1)° with respect to the pyrazolyl ring. The phenyl and tolyl substituents are aligned at 48.9 (1) and 44.5 (1)° with respect to the pyrazolyl ring. Weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonding is present in the crystal structure.


Elevated interleukin-1 receptor antagonist levels in pediatric sepsis syndrome.
To measure plasma levels of interleukin-1 beta, interleukin-1 receptor antagonist (IL-Ira), and tumor necrosis factor alpha in children with sepsis syndrome. A prospective, observational study of 14 patients aged 5 months to 13 years with sepsis syndrome admitted to a pediatric intensive care unit. Cytokine levels were measured by enzyme-linked immunosorbent assay at baseline and at a 12, 24, and 48 hours and compared with the levels of 21 age-matched control subjects. The mean pediatric risk of mortality score was 16.1. Bacterial and viral sepsis was confirmed in five and three patients, respectively. Compared with the levels in the control subjects (mean level of IL-Ira: 654 pg/ml), the IL-Ira levels were elevated in the septic patients, with mean values of 17855 (p < 0.001), 12771 (p < 0.001), 9182 (p < 0.01), and 2296 pg/ml (p = not significant) at baseline and at 12, 24, and 48 hours, respectively. The IL-Ira level was greater than 1000-fold higher than the IL-1 beta level at all time points in 13 of 14 septic patients. At the time of hospital admission, circulating IL-Ira levels in a cohort of children with sepsis syndrome were at concentrations known to block IL-1 receptors. Thus additional benefit from exogenous IL-Ira therapy would be questionable. Further studies are indicated to determine whether there is a population of patients with sepsis who could benefit from administration of exogenous IL-Ira.


Endovascular Treatment of a Traumatic Middle Cerebral Artery Pseudoaneurysm with the Pipeline Flex Embolization Device.
Traumatic pseudoaneurysms of the proximal middle cerebral artery (MCA) segments are challenging to treat. We describe the management of traumatic internal carotid artery and MCA pseudoaneurysms with flow diversion. A 19-year-old man had sustained a gunshot wound to the head. Delayed digital subtraction angiography showed de novo formation of the left internal carotid artery ophthalmic segment and left MCA M2 segment pseudoaneurysms. We had initially performed coil embolization of the left MCA pseudoaneurysm. However, it had recurred 2 weeks later. We treated both pseudoaneurysms with flow diversion using the Pipeline Flex embolization device. The patient has continued with dual antiplatelet therapy of aspirin and ticagrelor. Follow-up digital subtraction angiography at 6 months showed complete obliteration of both pseudoaneurysms with patent parent vessels. The patient remained neurologically intact. Flow diversion can be an efficacious treatment of traumatic MCA pseudoaneurysms in appropriately selected cases. The risks versus benefits of dual antiplatelet therapy must be weighed in trauma settings.


The effect of the menstrual cycle on serum CA 125 levels: a population study.
Our objective was to assess the effect of the menstrual cycle on CA 125 levels in a population study. Serum CA 125 was measured in 1478 women, with day of menstrual cycle noted in 574 women. Repeat examination was performed in women with elevated results, and 40 of these women were tracked by weekly examination of CA 125 levels. A significant difference was demonstrated when midcycle samples were compared with day 1 and day 28 samples (p < 0.05). In spite of this significance the difference was not clinically useful. Elevated serum CA 125 (> 35 U/ml) levels were present in 77 (5.2%) of the premenopausal women. A significant variation was demonstrable with higher CA 125 levels about the time of menstruation in 29 of the 40 women tracked. This study suggests that in the population as a whole the effect of the menstrual cycle on serum CA 125 is not clinically significant, but single elevated levels in an individual may represent menstrual fluctuation.


Late complications after root coverage with two types of subepithelial connective tissue grafts, clinical and histopathological evaluation: A prospective cohort study.
This prospective cohort study evaluated late complications (LC) on recipient sites comparing two types of connective tissue grafts (CTG). Participants (n: 60) were treated with coronally advanced flap (CAF) plus CTG harvested by de-epithelialized technique (DE) (n:31) or two-parallel incision (PI) (n:29). Areas were evaluated to identify white discharge associated or not with gingival cul-de-sac. Patients were ordered in groups with (DE+and PI+) or without (DE- and PI-) LC. Biopsies for histopathological analysis in LC areas were proposed. Six cases exhibited LC, 5 in DE graft (DE+) and 1 in PI graft (PI+) group; 2 were diagnosed at 3 months postoperatively, 3 at 6 months and one at 12 months. The relative risk for LC was 1.7 times greater for DE graft (p: 0.01; CI: 1.10 to 2.72; RR>1). Differences were not observed for clinical outcomes after both types of CTGs (p > 0.05). Biopsies showed deep invagination of the epithelial lining suggesting cyst-like area/ cavity with keratin content and consolidated in fibrous connective tissue. After 24 months biopsied areas presented no recurrence of LC, in non-biopsied patients the clinical condition remained unchanged. Considering the limitations of this study, LC on recipient sites demonstrated no statistical difference between two types of CTG.


Na2 Ti3 O7 @N-Doped Carbon Hollow Spheres for Sodium-Ion Batteries with Excellent Rate Performance.
Uniform Na2 Ti3 O7 hollow spheres assembled from N-doped carbon-coated ultrathin nanosheets are synthesized. A unique multilayer structure of nanosheets is presumed to significantly reduce energy consumption during the diffusion process of sodium ions, while the carbon-coated structure can increase the overall conductivity. The as-prepared sample used as an anode in sodium-ion batteries exhibits the best rate performance ever reported for Na2 Ti3 O7 , delivering more than 60 mAh g-1 after 1000 continuous cycles at the high rate of 50 C, which was achieved due to its unique structure.


Use of tissue-plasminogen activator as a reporter gene.
Throughout the past six or seven years, our ability to study and understand the process of eukaryotic gene expression has been greatly enhanced by the use of reporter genes. In essence, a reporter gene encodes a protein product for which a sensitive and convenient assay is available. Transcription of the reporter is driven by the control sequences of interest, so that the level of reporter protein reflects the transcriptional activity, Reporter genes in present usage include the chloramphenicol acetyltransferase (CAT) (ref. 1; see elsewhere in this vol) ß-galactosidase (ß-gal) (ref. 2) and, more recently, luciferase genes (see elsewhere in this vol).


Recycling of organic wastes by employing Eisenia fetida.
This paper reports the recycling of nutrients by vermicomposting of cow dung (CD), poultry droppings (PD) and food industry sludge (FIS) employing earthworms (Eisenia fetida). A total of six vermicomposting units were established and dynamics of chemical and biological parameters has been studied for 13 weeks. The waste mixture containing 50% CD+25% PD+25% FIS had better fertilizer value among studied waste combinations. At the end of experiment, vermicomposts showed decrease in pH and organic C, but increase in EC, total Kjeldhal N, total available P and total K contents. The C:N ratio of final vermicomposts also reduced to 10.7-12.7 from 22.8 to 56 in different waste combinations. The earthworms have good biomass gain and cocoon production in all vermicomposting units but CD alone and 50% CD+25% PD+25% FIS were better than other studied combinations.


Do outcomes of psychiatric hospital treatment differ for migrants and non-migrants?
Providing effective treatment for immigrants is an increasing challenge for mental health services across Europe. Yet, little is known as to whether current practice is associated with different outcomes in migrant and non-migrant patients. We compared outcomes of inpatient psychiatric treatment for migrants and non-migrants in a sample from five European countries. Patients with psychotic disorders, affective disorders or anxiety/somatisation disorders admitted to routine psychiatric inpatient treatment were assessed in hospitals in Belgium, Germany, Italy, Poland and the United Kingdom. Treatment outcomes were satisfaction with care during hospitalisation, length of stay, readmission to hospital (any and, specifically, involuntary re-hospitalisation), as well as untoward incidents in a 1-year follow-up period. Outcomes were compared between patients born inside (non-migrants) and outside (migrants) the country of treatment, through mixed regression models. Across all sites, 985 migrant patients and 6298 non-migrant patients were included. After accounting for the influence of confounding patient characteristics, migrants reported significantly lower treatment satisfaction, but there were no significant differences for length of stay and re-hospitalisations, in general and involuntary ones. Migrants had a lower rate of suicide attempts, but there was no significant difference in other types of untoward incidents in the year following the index admission. The study suggests that migrants are less satisfied with their hospital treatment, there is no evidence that routine inpatient care as currently provided results overall in poorer objective outcomes for migrants than in non-migrant populations.


Bacteria repellent protein hydrogel decorated with tunable, isotropic, nano-on-micro hierarchical microbump array.
We report the development of ordered shape-controllable microbump structures on protein hydrogels using polystyrene honeycomb templates. Addition of protein nanogels results in the formation of hierarchical nano-on-micro structures and increases surface hydrophilicity by over 55%, exhibiting bacteria repellency 100 times stronger than a flat hydrogel surface composed of the same protein.


Unusual presentation of cutaneous metastatic malignant melanoma.
This report describes an unusual presentation of cutaneous metastases suspected to have occurred through lymphatic spread in a patient with malignant melanoma. Punctate papular skin lesions correlated histologically with small tumor foci in the papillary dermis.


Polymorphisms in the interleukin 3 gene show strong association with susceptibility to Graves' disease in Chinese population.
Graves' disease (GD) is a common organ-specific autoimmune disorder, which is multifactorial and develops in genetically susceptible individuals. We had earlier mapped a susceptibility locus for GD to chromosome 5q31-33 in a linkage study. Here we used tag single-nucleotide polymorphisms (SNPs) to search for genetic variants associated with GD, and examined 19 functional candidate genes in this chromosomal region. We identified 192 polymorphisms by re-sequencing the candidate genes, and selected 51 tagSNPs to genotype in a case-control collection of 1118 south Han Chinese subjects (428 cases and 690 controls). Initial analysis suggested that a non-synonymous SNP rs40401 (P27S) of interleukin 3 (IL3) was associated with GD, and further fine-mapping showed that rs40401, or its perfect proxy SNP rs31480 in the 5' flanking region of IL3, fully accounted for the association signal at this locus. We replicated significant association of rs40401 with GD in an independent sample collection of 839 north Han Chinese subjects. A combined analysis revealed strong validation of this association (odds ratio (OR(common))=1.63, combined P (P(comb))=4 x 10(-6) in the Recessive disease model). This study provides convincing evidence that the IL3 gene is a susceptibility locus for GD in the Chinese population.


Essential medicines for the whole world.
The concept of essential medicines is as relevant to the whole world now as it was for some countries in 1975 when the concept was developed. Basically, the concept is that medicines needed to satisfy the priority health-care needs of a population should be made available at all times to everyone in the population within the context of a functioning health-care system.


Engineering Perspective on Cardiovascular Simulations of Fontan Hemodynamics: Where Do We Stand with a Look Towards Clinical Application.
Cardiovascular simulations for patients with single ventricles undergoing the Fontan procedure can assess patient-specific hemodynamics, explore surgical advances, and develop personalized strategies for surgery and patient care. These simulations have not yet been broadly accepted as a routine clinical tool owing to a number of limitations. Numerous approaches have been explored to seek innovative solutions for improving methodologies and eliminating these limitations. This article first reviews the current state of cardiovascular simulations of Fontan hemodynamics. Then, it will discuss the technical progress of Fontan simulations with the emphasis of its clinical impact, noting that substantial improvements have been made in the considerations of patient-specific anatomy, flow, and blood rheology. The article concludes with insights into potential future directions involving clinical validation, uncertainty quantification, and computational efficiency. The advancements in these aspects could promote the clinical usage of Fontan simulations, facilitating its integration into routine clinical practice.


Does nasal surgery improve multilevel surgical outcome in obstructive sleep apnea: A multicenter study on 735 patients.
Does nasal surgery affect multilevel surgical success outcome. Prospective eight country nonrandomized trial of 735 obstructive sleep apnea (OSA) patients, who had multilevel palate and/or tongue surgery, divided into two groups, with or without nose surgery. There were 575 patients in nose group, 160 patients in no nose group. The mean age for nose group 44.6 ± 11.4, no nose group 44.2 ± 11.8. Mean preoperative BMI for nose group 27.5 ± 3.6, no nose group 27.5 ± 4.1, mean postoperative BMI nose group 26.3 ± 3.7, no nose group 27.1 ± 3.8 (P = .006). Mean preoperative AHI nose group 32.7 ± 19.4, no nose group 34.3 ± 25.0 (P = .377); and mean postoperative AHI nose group 13.5 ± 10.2, no nose group 17.1 ± 16.0 (P = .001). Mean preoperative ESS nose group was 11.3 ± 4.7, no nose group was 10.4 ± 5.4 (P = .051); and mean postoperative ESS nose group was 5.3 ± 3.2, no nose group was 6.7 ± 2.8 (P = .001). The nose group had higher percentage change (adjusted for age, gender, BMI) in AHI (33.7%, 95% CI 14% to 53.5%) compared to the no nose group (P = .001); the nose group also had more percentage change in ESS (37%, 95% CI 23.6% to 50.3%) compared to the no nose group (P < .001). Change in BMI did not affect AHI nor ESS change (Cohen effect 0.03 and 0.14, respectively). AHI change in both groups were also statistically significant in the mild OSA (P = .008) and the severe OSA (P = .01). Success rate of surgery for the nose group 68.2%, while the no nose group 55.0% (P = .002). Combining nose surgery in multilevel surgery improves surgical success. IIC.


Implementation of community-based management of severe acute malnutrition in conflict affected regions: a case of South Kordofan, Sudan.
Malnutrition is the major cause of mortality and morbidity globally with undernutrition contributing about 45% of all deaths of under five children. Besides the direct effects of protracted conflicts, the macroeconomic crisis that has greatly increased the national inflation rate hence devastating the purchasing power, the COVID-19 outbreak, flooding, and the Desert Locusts have contributed to a food security emergency. Besides being among the most under resourced states, South Kordofan has experienced years of conflict resulting in displacement of people and extensive infrastructure destruction with high rates of malnutrition. The state currently has 230 health facilities and out of these, only 140 are providing outpatient therapeutic programme centres with 28.6% (40) of these being operated by the state ministry of health and the rest by the international non-governmental organizations. Limited resources leading to donor dependence, limited accessibility due to insecurity and floods, poor referral system and gaps in continuity of care, lack of operational and implementation research data and limited integration of management of malnutrition in other health services have negatively affected effective implementation. Ensuring effective and efficient community based management of acute malnutrition, implementation needs action beyond the health sector with a multi-sectoral and integration approach. Federal and state development frameworks should ensure a comprehensive multi-sectoral nutrition policy with strong political commitment and allocation of adequate resources to ensure integrated and quality implementation.


Effect of Visibility of the Ciliary Body Processes on Ocular Biometric Parameters in Patients with Primary Angle Closure.
To evaluate the differences in ocular biometric parameters between eyes with primary angle closure (PAC) with and without visible ciliary body processes (CBP) (PAC+CBP and PAC-CBP) and normal open-angle controls. Cross-sectional study. Eyes with PAC and normal open-angle controls underwent detailed ocular examinations and gonioscopy to determine the visibility of the CBP. The following ocular biometric parameters were determined using A-scan ultrasound biometry: axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and vitreous length (VL). The lens-axial length factor (LAF) and relative lens position (RLP) were also calculated. Continuous variables were assessed by analysis of variance with Bonferroni correction. Multiple linear regression analysis was performed to adjust for confounding factors. Area under the receiver operating characteristic curves were calculated to determine the diagnostic capability of biometric parameters. 84 PAC+CBP eyes, 57 PAC-CBP eyes, and 32 normal open angle control eyes were evaluated. The means of the ocular biometric values were significantly different among the three groups. AL, ACD, LT, VL, LAF, and RLP were also significantly different among the three groups in the multivariate regression analysis. AL, ACD, and VL were lower in the PAC+CBP group and LT, RLP, and LAF were greater in the PAC+CBP group than in the PAC-CBP and control groups. LAF ≥ 2.4 is the cutting point with the highest sensitivity and specificity to differentiate PAC+CBP from PAC-CBP. The ocular biometric parameters in the PAC+CBP group were more strongly associated with a crowded anterior segment than in the other groups. Visibility of CBP in PAC-affected eyes may serve as a surrogate for an anterior segment crowding mechanism and help to select the most appropriate treatment in individual cases.


Neural correlates of concurrent sound perception: A review and guidelines for future research.
The perception of concurrent sound sources depends on processes (i.e., auditory scene analysis) that fuse and segregate acoustic features according to harmonic relations, temporal coherence, and binaural cues (encompass dichotic pitch, location difference, simulated echo). The object-related negativity (ORN) and P400 are electrophysiological indices of concurrent sound perception. Here, we review the different paradigms used to study concurrent sound perception and the brain responses obtained from these paradigms. Recommendations regarding the design and recording parameters of the ORN and P400 are made, and their clinical applications in assessing central auditory processing ability in different populations are discussed.


Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways.
Neuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson's. The symptoms in Parkinson's including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT). Sixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, D0); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19-21, D21), completion (days 38-42, D42), and four weeks post-EBRT (days 68-72, D72). Gene expression profiling using microarray analysis was performed from peripheral blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach. Microarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95-fold change at D21 from baseline. SNCA expression was confirmed by qPCR (p<0.001) and ELISA (p<0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r=0.55, p<0.05) and plasma α-synuclein concentrations on D42 of EBRT (r=0.54, p=0.04). Fatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population.


Morpho-physiological and biochemical response of wheat to various treatments of silicon nano-particles under drought stress conditions.
Silicon nanoparticles (Si-NPs) have shown their potential for use in farming under water-deficient conditions. Thus, the experiment was accomplished to explore the impacts of seed priming of Si-NPs on wheat (Triticum aestivum L.) growth and yield under different drought levels. The plants were grown in pots under natural ecological environmental conditions and were harvested on 25th of April, 2020. The results revealed that seed priming of Si-NPs (0, 300, 600, and 900 mg/L) suggestively improved, the spike length, grains per spike, 1000 grains weight, plant height, grain yield, and biological yield by 12-42%, 14-54%, 5-49%, 5-41%, 17-62%, and 21-64%, respectively, relative to the control. The Si-NPs improved the leaf gas trade ascribes and chlorophyll a and b concentrations, though decreased the oxidative pressure in leaves which was demonstrated by the diminished electrolyte leakage and upgrade in superoxide dismutase and peroxidase activities in leaf under Si-NPs remedies over the control. The outcomes proposed that Si-NPs could improve the yield of wheat under a dry spell. In this manner, the utilization of Si-NPs by seed priming technique is a practical methodology for controlling the drought stress in wheat. These findings will provide the basis for future research and helpful to improve the food security under drought and heat related challenges.


A comparison of enhanced green fluorescent protein expression induced by immediate-early cytomegalovirus (IE-CMV) and gG pseudorabies virus (gG-PRV) promoters, using pseudorabies virus amplicons as vectors.
This study compares the expression efficiencies of the IE-CMV and gG-PRV promoters following their transfection into cultured human and monkey cells, using pseudorabies virus amplicons as vectors and enhanced green fluorescence protein (EGFP) as an expression marker. EGFP expression was similarly strong with both promoters. Pseudorabies virus amplicons appear to be useful vectors in gene expression studies due to their replication in the presence of helpers and their wide range of cellular hosts.


Facilitated thyrotropin release after retrochiasmatic hypothalamic knife cuts.
Diencephalic structures that influence plasma thyrotropin (TSH) in male rats under pentobarbital anesthesia (35 mg/kg, IP) were studied by combining medial preoptic area-suprachiasmatic nucleus (MPOA-Sch) bilateral electrical stimulation (monophasic pulses, 200 microA at 50 Hz, 30 min) with progressive midline lesions produced by a retractable Halász knife. Plasma TSH was measured by radioimmunoassay just before (0 time) and at 30, 60 and 90 min after the beginning of stimulation. Rats that had received only sham surgical procedures 90 days prior to stimulation were characterized by a more than 2-3 fold elevation in basal (0 time) plasma TSH levels when compared to those found in intact control rats and expected elevations in plasma TSH at 30 min after stimulation were eliminated. After a small frontal cut (1.3 FC), 0 time plasma TSH levels increased more tha 4-fold above those of controls in association with a facilitation of stimulated release of TSH. When the knife blade radius was 1.5 mm (1.5 FC) the facilitation of TSH release after stimulation occurred again; however, 0 time plasma TSH concentrations in 1.5 FC rats were not different from control levels. These effects of midline cortical, thalamic and hypothalamic damage on TSH release required the passage of more than 12 days after brain surgery. Collectively, these findings suggest potential neural elements that are inhibitory for 'basal' and 'phasic' TSH release which are in close proximity to a separate excitatory neural system and which can be activated by MPOA-Sch stimulation.


New glacier evidence for ice-free summits during the life of the Tyrolean Iceman.
Detailed knowledge of Holocene climate and glaciers dynamics is essential for sustainable development in warming mountain regions. Yet information about Holocene glacier coverage in the Alps before the Little Ice Age stems mostly from studying advances of glacier tongues at lower elevations. Here we present a new approach to reconstructing past glacier low stands and ice-free conditions by assessing and dating the oldest ice preserved at high elevations. A previously unexplored ice dome at Weißseespitze summit (3500 m), near where the "Tyrolean Iceman" was found, offers almost ideal conditions for preserving the original ice formed at the site. The glaciological settings and state-of-the-art micro-radiocarbon age constraints indicate that the summit has been glaciated for about 5900 years. In combination with known maximum ages of other high Alpine glaciers, we present evidence for an elevation gradient of neoglaciation onset. It reveals that in the Alps only the highest elevation sites remained ice-covered throughout the Holocene. Just before the life of the Iceman, high Alpine summits were emerging from nearly ice-free conditions, during the start of a Mid-Holocene neoglaciation. We demonstrate that, under specific circumstances, the old ice at the base of high Alpine glaciers is a sensitive archive of glacier change. However, under current melt rates the archive at Weißseespitze and at similar locations will be lost within the next two decades.


Development of a Patient-Reported Outcome Measure to Assess Symptoms Associated with Cataract Surgery and Intraocular Lens Implants.
To develop a standardized patient-reported outcome measure of visual perceptions and symptoms for implanted premium and monofocal intraocular lenses (IOLs). Observational study before and after IOL implants to assess the measure and symptom experience. Adults scheduled for binocular implantation of the same IOL type completed the survey at baseline prior to surgery (n = 716) and postoperatively (n = 554). Most respondents were female (64%), White (81%), 61 or older (89%), and had some college or more education (62%). Administration was by web survey with mail follow-up and phone reminders. Frequency, severity, and level of symptom bother in the last 7 days for 14 symptoms: (1) glare, (2) hazy vision, (3) blurry vision, (4) starbursts, (5) halos, (6) snowballs, (7) floaters, (8) double images, (9) rings and spider webs, (10) distortion, (11) light flashes with eyes closed, (12) light flashes with eyes open, (13) shimmering images, and (14) dark shadows. The median correlation among having 14 symptoms at baseline was only 0.19. Mean uncorrected binocular visual acuity improved from a preoperative value of 0.47 logarithm of the minimum angle of resolution (logMAR; Snellen 20/59) to a postoperative value of 0.12 (20/26) and best-corrected binocular visual acuity improved from 0.23 logMAR (20/34) preoperative to 0.05 logMAR (20/22) postoperative. The most bothersome symptoms were reduced after surgery: preoperative/postoperative glare (84%/36%), blurry vision (68%/22%), starbursts (66%/28%), hazy vision (63%/18%), snowballs (55%/17%), and halos (52%/22%). All symptoms decreased significantly (P < 0.0001) from before to after surgery except for dark crescent-shaped shadows (4%/4%). The percentage of symptoms rated as quite a bit or extremely bothersome declined from before to after surgery except for dark crescent-shaped shadows (29%/32%): blurry vision (54%/15%), snowballs (52%/14%), glare (49%/15%), and halos (46%/14%). Having monofocal IOL implants was associated with significantly more reduction in halos, starbursts, glare, and rings and spider webs, but less improvement in self-reported general vision. This study provides support for the 37-item Assessment of IntraOcular Lens Implant Symptoms (AIOLIS) instrument for use to assess symptoms and general perceptions of vision in clinical studies and clinical care. Proprietary or commercial disclosure may be found after the references.


Growth after renal transplantation: correlation with immunosuppressive therapy.
The growth data for children transplanted between 1973 and 1987 were analysed according to their immunosuppressive regimen. All patients treated before 1985 received conventional treatment (prednisone, azathioprine); 37% of the prepubertal children with a follow-up of longer than 2 years showed catch-up growth, and 30% of the pubertal children exhibited a normal adolescent growth spurt. Reduced renal function and corticosteroid treatment are the two main causes of growth delay. The children transplanted between January 1985 and September 1987 were given either triple therapy [cyclosporine (CsA), prednisone, azathioprine] or conventional treatment after randomisation. Growth data were significantly better with CsA. The mean height gain for prepubertal children was +0.24 SD/year on triple therapy and +0.14 SD/year on conventional therapy during the 1st year after transplantation; and 0.4 SD/year and 0 SD/year during the 2nd year (P less than 0.05). The mean height gain for pubertal children was 5.6 cm/year on triple therapy and 3.6 cm/year on conventional therapy (P less than 0.005). The patients on triple therapy also received a significantly lower cumulative dose of prednisone. Some selected patients on triple therapy were taken off prednisone 12 months after transplantation. All patients showed catch-up growth (+0.83 SD/year in prepubertal children, 7.2 cm/year in pubertal children). In conclusion, protocols including CsA and the lowest cumulative dose of steroid (with alternate-day or even steroid withdrawal) allow the best restoration of growth.


Infections in burn patients--experience in a tertiary care hospital.
A retrospective study was conducted at the Kanchi Kamakoti Childs Trust Hospital to analyze the bacterial isolates from the wounds of patients admitted to the Burns Unit and to determine the sensitivity patterns of the commonly cultured organisms over a 6-year period, December 1998 to December 2004. A total of 535 samples were analysed. Single isolates were more common. Pseudomonas was the most commonly cultured organism followed by Staphylococcus aureus. Escherechia coli and Klebsiella were seen in equal numbers. ESBL rates were 37%. Antibiotic sensitivity patterns and periodic ESBL surveillance helped in selection of appropriate antibiotics.


Dose-response association between fluid overload and in-hospital mortality in critically ill patients: a multicentre, prospective, observational cohort study.
Fluid management is important in ensuring haemodynamic stability in critically ill patients, but can easily lead to fluid overload (FO). However, the optimal fluid balance plot or range for critically ill patients is unknown. This study aimed to explore the dose-response relationship between FO and in-hospital mortality in critically ill patients. Multicentre, prospective, observational study. Eighteen intensive care units (ICUs) of 16 tertiary hospitals in China. Critically ill patients in the ICU for more than 3 days. FO was defined as the ratio of the cumulative fluid balance (L) and initial body weight (kg) on ICU admission, expressed as a percentage. Maximum FO was defined as the peak value of FO during the first 3 days of ICU admission. Logistic regression models with restricted cubic splines were used to explore the pattern and magnitude of the association between maximum FO and risk of in-hospital mortality. Age, sex, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score on admission, main diagnosis on admission to ICU, comorbidities, time of maximum FO, mechanical ventilation, renal replacement therapy, use of vasopressors and centres were adjusted in multivariable analysis. A total of 3850 patients were included in the study, 929 (24.1%) of whom died in the hospital. For each 1% L/kg increase in maximum FO, the risk of in-hospital mortality increased by 4% (adjusted HR (aHR) 1.04, 95% CI 1.03 to 1.05, p<0.001). A maximum FO greater than 10% was associated with a 44% increased HR of in-hospital mortality compared with an FO less than 5% (aHR 1.44, 95% CI 1.27 to 1.67). Notably, we found a non-linear dose-response association between maximum FO and in-hospital mortality. Both higher and negative fluid balance levels were associated with an increased risk of in-hospital mortality in critically ill patients. ChiCTR-ECH-13003934.


Identification of Beclin-1 from orange-spotted grouper (Epinephelus coioides) involved in viral infection.
Beclin-1 is an essential autophagic regulator that plays diverse roles in physiology and disease. However, reports about the function of fish Beclin-1 during pathogen infection are still very limited. In this study, a Beclin-1 homolog (EcBeclin-1) from orange-spotted grouper (Epinephelus coioides) was identified and its roles in viral infection were investigated. EcBeclin-1 encoded 447amino acids protein with a BH3 domain, a CCD domain and an ECD domain, which shared high identities (97%-82%) with reported Beclin-1 proteins from mammal to fish. Quantitative real-time PCR (qRT-PCR) analysis revealed that EcBeclin-1 was predominantly expressed in brain and muscle of healthy grouper. Using fluorescence microscopy, we found that EcBeclin-1 was co-localized with endoplasmic reticulum (ER) in grouper spleen cells (EAGS). After red-spotted grouper nervous necrosis virus (RGNNV) infection in vitro, EcBeclin-1 transcript was significantly up-regulated, implying that EcBeclin-1 might be involved in viral infection. Furthermore, the in vitro studies of EcBeclin-1 overexpression promoted RGNNV induced autophagy, as well as the expression of coat protein (CP) and RNA-dependent RNA polymerase (RdRp). The overexpression of EcBeclin-1 suppressed the expressions of interferon pathway-related factors, inflammatory-related factors and activities of NF-κB and ISRE. Additionally, EcBeclin-1 could interact with EcBcl-xL in vitro. These data suggest that EcBeclin-1 affect viral replication through modulating IFN and inflammatory responses, as well as virus-induced cell death, which will help us to further explore the immune response of fish during viral infection.


Early life stress and substance use disorders: The critical role of adolescent substance use.
Early life stress (ELS) is a well-established risk factor for many psychiatric and medical disorders, including substance use disorders (SUDs). The relationship between ELS and SUDs is complex and there are likely multiple pathways from ELS to adverse substance use outcomes. The association between ELS and substance use emerges in adolescence. Adolescence is a critical period in development during which substance exposure markedly increases risk for SUDs. Therefore, this review focuses on the literature supporting the hypothesis that ELS increases risk for the development of SUDs through its influence on adolescent substance use. We discuss studies substantiating the role of ELS in adolescent substance use and explore how internalizing and externalizing psychopathology may be antecedents of substance use in adolescence. We examine clinical work suggesting ELS sculpts the Hypothalamic-Pituitary-Adrenal (HPA) Axis and developing brain-particularly subcortical brain regions that underlie stress response, mesocorticolimbic brain systems associated with reward sensitivity, and prefrontal regions that underlie executive control-in a way that increases risk for adolescent substance use and SUDs. We further explore how substance use during adolescence alters structure and function of these same systems, and how brain changes following ELS and adolescent substance use may independently, additively, or interactively contribute to risk for addiction. We conclude by discussing how the current literature can inform interventions aimed at reducing risk for SUDs in individuals with a history of ELS.


Transcriptome analysis of the uterus of hens laying eggs differing in cuticle deposition.
Avian eggs have a proteinaceous cuticle. The quantity of cuticle varies and the deposition of a good cuticle in the uterus (Shell-gland) prevents transmission of bacteria to the egg contents. To understand cuticle deposition, uterus transcriptomes were compared between hens with i) naturally good and poor cuticle and, ii) where manipulation of the hypothalamo-pituitary-gonadal-oviduct axis produced eggs with or without cuticle. The highest expressed genes encoded eggshell matrix and cuticle proteins, e.g. MEPE (OC-116), BPIFB3 (OVX-36), RARRES1 (OVX-32), WAP (OVX-25), and genes for mitochondrial oxidative phosphorylation, active transport and energy metabolism. Expression of a number of these genes differed between hens laying eggs with or without cuticle. There was also a high expression of clock genes. PER2, CRY2, CRY1, CLOCK and BMAL1 were differentially expressed when cuticle deposition was prevented, and they also changed throughout the egg formation cycle. This suggests an endogenous clock in the uterus may be a component of cuticle deposition control. Cuticle proteins are glycosylated and glycosaminoglycan binding genes had a lower expression when cuticle proteins were deposited on the egg. The immediate early genes, JUN and FOS, were expressed less when the cuticle had not been deposited and changed over the egg formation cycle, suggesting they are important in oviposition and cuticle deposition. The uterus transcriptome of hens with good and poor cuticle deposition did not differ. We have gained insights into the factors that can affect the production of the cuticle especially clock genes and immediate early genes. We have demonstrated that these genes change their expression over the period of eggshell formation supporting their importance. The lack of differences in expression between the uterus of hens laying eggs with the best and worse cuticle suggest the genetic basis of the trait may lie outside the oviduct.


Dietary Administration of Probiotic Aeromonas veronii V03 on the Modulation of Innate Immunity, Expression of Immune-Related Genes and Disease Resistance Against Aeromonas hydrophila Infection in Common Carp (Cyprinus carpio).
This study investigates the effects of dietary Aeromonas veronii V03 supplementation on growth performances, innate immunity, and expression of immune-related genes in lymphoid organs of Cyprinus carpio and resistance to Aeromonas hydrophila infection. Fish were fed for 4 weeks with basal diet (BD; without probiotic), and experiment diet containing different doses of A. veronii V03 at 3.2 × 107 (DI) and 3.5 × 109 (DII) CFU g-1 of diet. At the end of the probiotic feeding trial, fish were challenged with A. hydrophila, and the percentage of survival rates was recorded over 7 days. Results revealed that fish fed with A. veronii V03 demonstrated a significant improvement in growth and enhancement of innate immunity, including respiratory burst, myeloperoxidase, and lysozyme activities, and total immunoglobulin level compared with BD fed to fish. Relatively, expression of cytokines (MyD88, IL-1β1, IL-8, and IL-10) and c- and g-type lysozymes were significantly up- and downregulated in lymphoid organs of fish. Moreover, dietary supplementation of A. veronii V03 exhibited significantly (p < 0.001) higher survival rates of DI (90%) and DII (96.66%) compared with BD (53.33%) fed fish against A. hydrophila infection. These findings help to understand the effects of probiotic A. veronii V03 administrated feed influences on growth and ailment resistance to A. hydrophila infection by regulating innate and systemic immunity in common carp fish.


A synthetic peptide metalloproteinase inhibitor, but not TIMP, prevents the breakdown of proteoglycan within articular cartilage in vitro.
IL1-stimulated pig articular cartilage fragments were cultured in the and absence of various metalloproteinase inhibitors. Tissue inhibitor of metalloproteinases (TIMP) was unable to stop the release of proteoglycan from the cartilage. Incubation of cartilage with a potent synthetic metalloproteinase inhibitor inhibited the release of proteoglycan in a dose-dependent fashion. The results suggest that low-M(r) metalloproteinase inhibitors may have therapeutic potential in limiting connective tissue breakdown in conditions such as rheumatoid arthritis.


Drug treatments for covid-19: living systematic review and network meta-analysis
To compare the effects of treatments for coronavirus disease 2019 (covid-19). Living systematic review and network meta-analysis. WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis. Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. 463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty). Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19. This review was not registered. The protocol is publicly available in the supplementary material. This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.


Microplastic uptake and gut retention time in Japanese anchovy (Engraulis japonicus) under laboratory conditions.
To explore the impact of microplastic (MP) pollution on planktivorous fish, we examined the uptake and retention of MPs by Japanese anchovy (Engraulis japonicus) under laboratory conditions. MP uptake was size selective in adult anchovy-0.3-mm MPs were taken up in significantly larger amounts than 0.85-mm MPs-but not in juveniles. There were no significant differences in the uptake of MPs of three different colors, suggesting that anchovy do not select for MP coloration. More than 90% of the MPs were excreted within 20 h of ingestion, indicating that MP retention time is similar to the processing time of food items. Our findings suggest that Japanese anchovy tend to take up MPs that are equivalent in size to prey items, but that the impacts of MP ingestion are likely to be limited under the current state of oceanic MP contamination.


Assessment of protein solution versus crystal structure determination using spin-diffusion-suppressed NOE and heteronuclear relaxation data.
A spin-diffusion-suppressed NOE buildup series has been measured for E. coli thioredoxin. The extensive 13C and 15N relaxation data previously reported for this protein allow for direct interpretation of dynamical contributions to the 1H-1H cross-relaxation rates for a large proportion of the NOE cross peaks. Estimates of the average accuracy for these derived NOE distances are bounded by 4% and 10%, based on a comparison to the corresponding X-ray distances. An independent fluctuation model is proposed for prediction of the dynamical corrections to 1H-1H cross-relaxation rates, based solely on experimental structural and heteronuclear relaxation data. This analysis is aided by the demonstration that heteronuclear order parameters greater than 0.6 depend only on the variance of the H-X bond orientation, independent of the motional model in either one- or two-dimensional diffusion (i.e., 1-S2 = 3/4 sin2 2 theta sigma). The combination of spin-diffusion-suppressed NOE data and analysis of dynamical corrections to 1H-1H cross-relaxation rates based on heteronuclear relaxation data has allowed for a detailed interpretation of various discrepancies between the reported solution and crystal structures.


Cost-Effectiveness of Utilization of Hepatitis B Virus-Positive Liver Donors for HBV-Negative Transplant Recipients.
Utilization of hepatitis B virus (HBV)-infected donors represents an opportunity to expand the liver transplantation (LT) donor pool. However, benefits of accepting HBV-positive donors for HBV-negative candidates, potentially expanding the donor pool resulting in earlier transplantation, must be balanced with costs of lifelong antiviral therapy. The aim of this study was to evaluate cost-effectiveness of this strategy. We developed a Markov model with two strategies, transplant with (1) a HBV-positive donor versus and (2) a HBV-negative donor for a HBV-negative LT candidate. A healthcare system perspective was utilized, effectiveness measured in quality-adjusted life-years, and costs in 2018 USD. In the base-case, the HBV-positive donor strategy is more effective (gain of 0.46 QALYs), but $26,159 more expensive, yielding an incremental cost-effectiveness ratio (ICER) of $57,389/QALY. However, increasing the candidate's Model for End-Stage Liver Disease score resulted in increasing cost-effectiveness, ICER of $69,507/QALY (MELD 6-10) to $47,385/QALY (MELD > 30). Results were most sensitive to antiviral cost and cost after first year of LT. In probabilistic sensitivity analysis, the HBV-positive strategy was always more effective but more expensive, with average ICER of $64,883/QALY. This strategy was highly cost-effective (ICER < $50,000/QALY) 21% of the time and cost < $100/000/QALY 94% of the time. Consideration of these donors must be individualized to each candidate's severity of liver disease, associated costs, and personal preferences that impact quality of life. Expansion of the donor pool to include HBV-positive donors for appropriate recipients may be a cost-effective policy and may provide significant benefit for individual patients.


Home Health Care Is Associated With an Increased Risk of Emergency Department Visit, Readmission, and Cost of Care Without Reducing Risk of Complication Following Total Hip Arthroplasty: A Propensity-Score Analysis.
Home health services have long been implemented for patients to receive additional professional care and supervision following discharge from the hospital to theoretically reduce the risk of complications and health care utilizations. The aim of this investigation was to determine if patients assigned home health services exhibited lower rates of medical and surgical complications, health care utilizations, and costs of care following total hip arthroplasty. A large national database was retrospectively reviewed to identify all primary total hip arthroplasty patients from 2010 to 2019. Patients who received home health services were matched using a propensity score algorithm to a set of similar patients who were discharged home under self-care. We compared medical and surgical complication rates, emergency room visits, readmissions, and 90-day costs of care between the groups. Multivariate regression analyses were performed to determine the independent effect of home health services on all outcomes. There were 7,243 patients who received home health services and were matched to 72,430 patients who were discharged home under self-care. Patients who received home health services had higher rates of emergency department visits at 30 days (Odds Ratio [OR] R statistical programming software v 3.6.1 [Lucent Technologies, New Providence, RJ] 1.1544; P = .002) as well as increased readmissions at 30 days (OR 1.137; P = .039); complication rates were similar between groups. Episode-of-care costs for home health patients were higher than those discharged under self-care ($14,236.97 versus $12,817.12; P < .001). Patients assigned home health care services exhibited higher costs of care without decreased risk of complications and had increased risk of early returns to the emergency department and readmissions.


[Hematomyelia in systemic lupus erythematosus and secondary antiphospholipid syndrome: case report].
Intraspinal hemorrhage is very rare and intramedullary hemorrhage, also called "hematomyelia," is the rarest form of intraspinal hemorrhage. There are few reports in medical literature. We report the case of a woman of 43 years with diagnosis of systemic lupus erythematosus and secondary antiphospholipid syndrome under anticoagulant therapy that presented hematomyelia. We describe the clinical course, the findings in the image studies and surgery, and the available information in the literature.


A Pilot Study of the Use of Dexmedetomidine for the Control of Delirium by Reducing the Serum Concentrations of Brain-Derived Neurotrophic Factor, Neuron-Specific Enolase, and S100B in Polytrauma Patients.
Delirium is very common among patients with polytrauma, although no suitable means exist to feasibly reduce the incidence and duration of delirium in these patients. Recent reports have suggested that continuous intravenous (IV) infusions of dexmedetomidine, rather than benzodiazepine, be administered for sedation to reduce the duration of delirium in this population. However, serum neuron-specific enolase (NSE), S100 calcium binding protein B (S100B), and brain-derived neurotrophic factor (BDNF) levels have not yet been investigated in polytrauma patients who received sedation with dexmedetomidine rather than other conventional sedatives. The aim of this study was to assess the association of blood BDNF, NSE, and S100B with the occurrence of delirium among polytrauma patients who had been sedated with dexmedetomidine. Consecutive patients were randomly assigned to 1 of 2 treatment study groups, namely the "dexmedetomidine group" or the "common group." This case-control study included 18 patients with delirium and 34 matched controls in a 63-bed general intensive care unit (ICU). Blood samples were collected from all patients upon ICU admission, on the day when delirium was diagnosed, and on days 3 and 5 following diagnosis. The serum levels of S100B, BDNF, and NSE were determined by enzyme-linked immunosorbent assay. The sedation levels and delirium were assessed using the Richmond Agitation and Sedation Scale and the Confusion Assessment Method for the ICU. The median BDNF, NSE, and S100B concentrations were significantly lower in the dexmedetomidine group than in the common group on the day when delirium was diagnosed and on the third day after delirium was diagnosed. The rate of delirium was significantly lower in the dexmedetomidine group than in the common group. There were clear differences in the BDNF, NSE, and S100B levels between the 2 groups on the fifth day after delirium was diagnosed. Our randomized controlled study suggests that the sedation of polytrauma patients with dexmedetomidine could help reduce the serum BDNF, S100B, and NSE levels, which appear to be associated with the occurrence of delirium in the dexmedetomidine group.


Detection of Unfolded Protein Response by Polymerase Chain Reaction.
The unfolded protein response is a cellular adaptive mechanism localized in the endoplasmic reticulum. It involves three phases: the detection of increased presence of unfolded proteins as a result of cellular stressors; the execution of an adaptive cascade of events aimed at the enhancement of proper protein folding and degradation of improperly folded proteins; and finally, when stress is not alleviated, the execution of programmed cell death. The main effectors of the UPR are transcription factors involved in the upregulation of either chaperone proteins or proapoptotic proteins. Two of these transcription factors are CHOP and the spliced variant of XBP-1 (XBP1s). In this chapter, we describe a quantitative PCR method to detect the upregulation of CHOP and XBP1s mRNA during Tunicamycin-induced UPR.


Inhibition of kinesin motor protein KIFC1 by AZ82 induces multipolar mitosis and apoptosis in prostate cancer cell.
Kinesin 14 family member KIFC1 is a mitotic kinesin which contains a C-terminal motor domain and plays a vital role for clustering the amplified centrosomes. Overexpression of KIFC1 in prostate cancer (PCa) cells showed resistance to docetaxel (DTX). The present study revealed that small KIFC1 inhibitor AZ82 suppresed the transcription and translation of KIFC1 significantly in PCa cells. AZ82 inhibited the KIFC1 expression both in the cytoplasm and nucleus of PCa cells. Inhibition of KIFC1 by AZ82 caused multipolar mitosis in PCa cells via de-clustering the amplified centrosomes and decreased the rate of cancer cell growth and proliferation. Moreover, depletion of KIFC1 reduced cells entering the cell cycle and caused PCa cells death through apoptosis by increasing the expression of Bax and Cytochrome C. Thereby, KIFC1 silencing and inhibition decreased the PCa cells survival by inducing multipolar mitosis as well as apoptosis, suggesting inhibition of KIFC1 using AZ82 might be a strategy to treat PCa by controlling the cancer cell proliferation.


Draft Genome Sequence of a Multidrug-Resistant Pseudomonas aeruginosa Strain Isolated from a Patient with a Urinary Tract Infection in Khartoum, Sudan.
Pseudomonas aeruginosa infection is difficult to treat due to the presence of antibiotic resistance determinants. Here, we report the genome sequence of a multidrug-resistant P. aeruginosa strain isolated from a patient with a urinary tract infection in 2015.


Potent osteogenic activity of a novel imidazobenzimidazole derivative, IBIP.
Bone mass is controlled by a balance between bone resorption and formation by osteoclasts and osteoblasts, respectively. An imbalance between osteoblasts and osteoclasts increases the risk of osteoporosis and fractures. Although inhibition of osteoclasts is beneficial for preventing and treating osteoporosis, enhanced bone formation through activation of osteoblast differentiation can be a more promising therapeutic approach. In this study, we attempted to isolate small molecules that promote osteoblast differentiation and found that IBIP (3-(2,3-dimethoxyphenyl)-1-[9-methyl-2-phenyl-9H-imidazo[1,2-a]benzimidazol-3-yl]-2-propen-1-one) was a potent activator of osteoblast differentiation. Upon bone morphogenetic protein-2 (BMP2) stimulation, IBIP promoted osteoblast differentiation and increased the expression of osteoblast-specific gene markers, such as osterix and alkaline phosphatase, in a dose-dependent manner. The phosphorylation of SMADs and extracellular signal-regulated kinase (ERK) increased after IBIP treatment. While enhanced SMAD phosphorylation by IBIP was abolished by a BMP inhibitor, IBIP-induced ERK phosphorylation was sustained in the presence of this inhibitor, but was decreased by an ERK kinase inhibitor. Suppression of IBIP-induced SMAD and ERK phosphorylation diminished osteoblast differentiation. Most importantly, IBIP enhanced bone formation and calcification in a BMP2-independent manner in vitro and advanced the skeletal development of zebrafish larvae in vivo. Collectively, IBIP may have beneficial effects on bone loss through potentiation of bone formation.


Burden of Pediatric Functional Gastrointestinal Disorder in an Emergency Department-A Single-Center Experience.
Functional gastrointestinal disorders (FGIDs) are recurrent or chronic gastrointestinal signs and symptoms in the absence of anatomical or biochemical alterations. They are commonly treated in outpatient setting but often present to emergency departments. We aimed to estimate the burden of pediatric FGID on a busy accident and emergency (A&E) department. Electronic patient records were used to retrospectively analyze the A&E attendances of 3866 patients presenting with either constipation or abdominal pain. Those found not to have a surgical/organic cause were assessed in terms of various parameters, that is, arrival times, wait times, and investigations performed. A total of 91.31% of the attendances relating to constipation or nonsurgical, nonorganic causes of abdominal pain were self-referred with only 3.64% arriving via ambulance, an average wait time ranging between 138 and 156 minutes, and a total of 1008 investigations carried out on patients presenting with these symptoms. A total of 63.65% of the patients were discharged without follow-up. Functional gastrointestinal disorders place considerable burden on the A&E, in terms of resource usage, time of clinicians, and financial strain. More education should be provided to families of those experiencing FGID in an outpatient setting to minimize A&E resource utilization. More research is needed to ascertain the true burden of FGIDs, both financially and in terms of time and resource.


Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development.
Adenosine receptors (ARs) are ubiquitously distributed throughout the mammalian body where they are involved in an extensive list of physiological and pathological processes that scientists have only begun to decipher. Resultantly, AR agonists and antagonists have been the focus of multiple drug design and development programmes within the past few decades. Considered to be a privileged scaffold in medicinal chemistry, the chalcone framework has attracted a substantial amount of interest in this regard. Due to the potential liabilities associated with its structure, however, it has become necessary to explore other potentially promising compounds, such as heterocycles, which have successfully been obtained from chalcone precursors in the past. This review aims to summarise the emerging therapeutic importance of adenosine receptors and their ligands, especially in the central nervous system (CNS), while highlighting chalcone and heterocyclic derivatives as promising AR ligand lead compounds.


Melatonin enhances adult rat hippocampal progenitor cell proliferation via ERK signaling pathway through melatonin receptor.
Melatonin, a neurohormone secreted mainly by the pineal gland, has a variety of physiological functions and neuroprotective effects. Previous studies have shown that melatonin could stimulate the proliferation of neural stem/progenitor cells (NS/PCs). Recent studies reported that the activities of mitogen-activated protein kinase (MAPK) of neural stem cells (NSCs) changed in response to the proliferative effect of melatonin. Therefore, the aim of the present study was to explore the proliferative mechanism mediated by melatonin on the adult rat hippocampal NS/PCs. Treatment with melatonin significantly increased the number of neurospheres in a concentration-dependent manner and up-regulated nestin protein. Pretreatment with luzindole, a melatonin receptor antagonist, and PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor, prevented the increase in the number of neurospheres formed by the activation of melatonin. The levels of phospho-c-Raf and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) increased when treated with melatonin. Pretreatment with luzindole or PD98059 prevented the melatonin-induced increase in these signaling molecules. The present results showed that melatonin could induce NS/PCs to proliferate by increasing phosphorylation of ERK1/2 and c-Raf through melatonin receptor. These results provide further evidence for a role of melatonin in promoting neurogenesis, adding to the remarkably pleiotropic nature of this neurohormone. This intrinsic modulator deserves further investigation to better understand its physiological and therapeutic implication.


Regional impairment of protein synthesis following brief cerebral ischemia in the gerbil.
Regional cerebral protein synthesis following brief ischemia was investigated in the Mongolian gerbil, utilizing L-[methyl-14C]methionine autoradiography. Transient ischemia was induced for 1, 2 or 3 min. At various recirculation periods up to 48 h, animals received a single dose of L-[methyl-14C]methionine and then were terminated 35 min later. Sham-operated animals showed a normal pattern of amino acid incorporation into the proteins of the brain. Following 1-min ischemia, the pattern of protein synthesis was similar to that in the sham-operated gerbils. Ischemia for 2 min, however, caused marked inhibition of protein synthesis in the neocortex, striatum, hippocampal CA1 sector and the thalamus at 1 h of recirculation. Extensive recovery of protein synthesis was found in the neocortex, the striatum, the hippocampal CA1 sector and the thalamus at 5-24 h of recirculation, but, a slight inhibition was detectable in the hippocampal CA1 sector in one of six animals. This inhibition had fully recovered at 48 h of recirculation. Following 3-min ischemia, severe impairment of protein synthesis was found in the neocortex, striatum, the whole hippocampus and the thalamus. After 5-24 h of recirculation, the protein synthesis in these regions had gradually recovered, except that complete lack of amino acid incorporation was seen in the hippocampal CA1 subfield. This impairment of protein synthesis in the hippocampal CA1 sector was not recovered at 48 h of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)


A GyrB-GyrA fusion protein expressed in yeast cells is able to remove DNA supercoils but cannot substitute eukaryotic topoisomerase II.
Type II topoisomerases are a highly conserved class of enzymes which transport one double-stranded DNA segment through a transient break in another. Whereas the eukaryotic enzymes are homodimers of a single polypeptide, their bacterial homologues are homodimers of two independently coded protein subunits. Unlike eukaryotic topoisomerase II and bacterial topoisomerase IV, DNA gyrase is a bacterial type II topoisomerase which specializes in intramolecular DNA transport. We have fused the Escherichia coli coding sequences for the proteins GyrB and GyrA, which comprise DNA gyrase. This fusion was expressed in yeast cells and yielded the expected full-length protein product. When it was expressed in Deltatop1- top2-4 yeast cells, the fusion protein compensated their slow growth and reverted their elevated chromosomal excision of ribosomal genes. Furthermore, it removed DNA positive supercoils. The fusion protein, however, was unable to complement the temperature-dependent lethality of top2-4 cells. Fusion of the E. coli GyrB and GyrA proteins leads to a catalytically active topoisomerase which compensates several phenotypic traits attributed to unconstrained DNA supercoiling in topoisomerase-deficient cells. However, since the fusion protein cannot substitute for topoisomerase II, it may be efficient in intramolecular but not intermolecular DNA passage, resembling the catalytic properties of DNA gyrase.


Characterization of iridium film as a stimulating neural electrode.
Iridium films having near-bulk properties were formed by electron-beam evaporation with simultaneous bombardment of Ar ion beam. The charge-injection capabilities of Ir film were investigated, and the detrusor pressure induced by S2 stimulation with Ir-coated Pt electrode was measured and compared with the uncoated Pt electrode. The charge densities of Ir film were continuously increased with increase in the number of cycles in 0.1 M H2SO4 due to the accumulation of the iridium oxide phase. The iridium oxide formed contained nano-pores, and oxides had different dielectric properties. The Ir film could inject various amounts of charge in physiological solution under the identical stimulating condition depending on the degree of activation in 0.1 M H2SO4. S2 stimulation by Ir-coated Pt electrode caused more efficient bladder contraction of the male dog than the uncoated Pt electrode under the identical stimulus condition.


Addressing Unmet Maternal Health Needs at a Pediatric Specialty Infant Care Clinic.
The objective of this intervention was to evaluate the feasibility of screening mothers of medically fragile infants in the domains of 1) depression, 2) tobacco exposure, and 3) family planning at a post-neonatal intensive care unit (NICU) developmental pediatric visit. Additionally, we sought to estimate the percentage who met criteria for further evaluation in the three domains assessed. A cross-sectional questionnaire was administered to 100 caregivers of medically fragile infants at a specialty, post-NICU clinic visit. Participants' responses in three domains were evaluated and appropriate referrals were provided. Analysis was then restricted to the 87 biological mothers who completed the screening. Study staff contacted the mothers 2 months later to determine whether services had been accessed and to assess overall satisfaction with the screening within the pediatric visit. Qualitative interviews were conducted with pediatric clinic staff. Screening questionnaires were completed by 87 biological mothers. Twenty-two mothers (25%) met referral criteria. Pediatric clinic staff and providers were comfortable administering the screening instrument, and there was minimal disruption to clinic flow. Mothers of medically fragile infants are likely to have unmet health care needs that can be identified at a specialty pediatric clinic visit. A screening and referral intervention can be implemented with minimal interruption in pediatric clinic flow and is acceptable to mothers and pediatric providers.


Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis.
The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. This study compared influenza-induced activation of inflammasome and innate immune signaling in human bronchial epithelial cells from volunteers with and without asthma and investigated the role of caspase-1 in epithelial cell antiviral defense. Differentiated primary human bronchial epithelial cells from volunteers with and without asthma were infected with influenza A virus. An inflammasome-specific quantitative real-time polymerase chain reaction array was used to compare baseline and influenza-induced gene expression profiles. Cytokine secretion, innate immune gene expression, and viral replication were compared between human bronchial epithelial cells from volunteers with and without asthma. Immunofluorescence microscopy was used to evaluate caspase-1 and PYCARD colocalization. Tracheal epithelial cells from caspase-1-deficient or wild-type mice were infected with influenza and assessed for antiviral gene expression and viral replication. Human bronchial epithelial cells from asthmatic volunteers had altered influenza-induced expression of inflammasome-related and innate immune signaling components, which correlated with enhanced production of IL-1β, IL-6, and TNF-α. Specifically, influenza-induced caspase-1 expression was enhanced and localization differed in human bronchial epithelial cells from asthmatic volunteers compared to volunteers without asthma. Influenza-infected tracheal epithelial cells from caspase-1-deficient mice had reduced expression of antiviral genes and viral replication. Caspase-1 plays an important role in the airway epithelial cell response to influenza infection, which is enhanced in asthmatic volunteers, and may contribute to the enhanced influenza-related pathogenesis observed in vivo.


STAT6 controls the stability and suppressive function of regulatory T cells.
Signal transducer and activator of transcription 6 (STAT6) promotes tumorigenesis by decreasing the Forkhead box P3+ (Foxp3+) cell frequency allowing for the infiltration of inflammatory cells during the early stages of colitis-associated cancer (CAC). In this study, we dissected the role of STAT6 in the generation of inducible in vitro regulatory T cells (iTregs) and peripheral in vivo Tregs (pTregs) under inflammatory conditions. In in vitro assays, when STAT6 was lacking, iTregs preserved a stable phenotype and expressed high levels of Foxp3 and CD25 during long expansion periods, even in the presence of IL-6. This effect was associated with increased in vitro suppressive ability, over-expression of programmed death-1 (PD-1), CTLA-4, and Foxp3, and decreased IFN-γ expression. Furthermore, iTregs developed during STAT6 deficiency showed a higher demethylation status for the FOXP3 Treg-specific demethylated region (TSDR), coupled with lower DNA methyltransferase 1 (DNMT1) mRNA expression, suggesting that STAT6 may lead to Foxp3 silencing. Using a mouse model of CAC, the STAT6-/- pTregs expressed a more activated phenotype at the intestine, had higher suppressive capacity, and expressed more significant levels of PD-1 and latency-associated peptide of TGF-β (LAP) associated with their ability to attenuate tumor development. These data suggest that STAT6 signaling impairs the induction, stability, and suppressive capacity of Tregs developed in vitro or in vivo during gut inflammation.


How to diagnose an acutely inflamed appendix; a systematic review of the latest evidence.
Acute appendicitis is the most common condition that presents with an acute abdomen needing emergency surgery. Despite this common presentation, correctly diagnosing appendicitis remains a challenge as clinical signs or positive blood results can be absent in 55% of the patients. The reported proportion of missed diagnoses of appendicitis ranges between 20% and 40%. A delay or mis-diagnosis of appendicitis can result in severe complications such as perforation, abscess formation, sepsis, and intra-abdominal adhesions. Literature has shown that patients who had a negative appendectomy suffer post-op complications and infections secondary to hospital stays; there have even been reported cases of fatality. It is therefore crucial that timely and accurate diagnosis of appendicitis is achieved to avoid complications of both non-operating as well as unnecessary surgical intervention. The aim of this review is to systematically report and analyse the latest evidence on the different approaches used in diagnosing appendicitis. We include discussions of clinical scoring systems, laboratory tests, latest innovative bio-markers and radiological imaging.


Effect of sintering condition and low-temperature degradation on the flexural strength and phase transformation of zirconia.
The traditional sintering of zirconia takes an extended time, and accelerated treatments have been developed to reduce treatment time and manufacturing costs. Studies evaluating the effect of sintering time on the mechanical properties of zirconia are lacking. The purpose of this in vitro study was to evaluate the effect of the sintering condition and the low-temperature degradation (LTD) of zirconia on the flexural strength of monolithic zirconia. Zirconia specimens (LUXEN Enamel) were sintered at 1500 °C, 1530 °C, and 1560 °C for 4, 5, 6, 7, and 12 hours and subjected to LTD (n=10). Control specimens were assessed in the nontreated condition. The 3-point flexural strength was measured by using a universal testing machine. The crystal phases of the specimens were compared and quantitatively analyzed through X-ray diffraction (XRD) analysis, and the crystal grain size was measured by using a field emission scanning electron microscope (FE-SEM). Two-way ANOVA and the independent sample t test were used to analyze the experimental results (α=.05). In the group not subjected to LTD, there was no difference in flexural strength according to the change in sintering temperature and sintering time (P>.05). The group subjected to LTD showed a difference in flexural strength according to sintering time difference (P<.001). The flexural strength of the zirconia with LTD exposure increased compared with that of the zirconia specimen not subjected to LTD (P<.001). With LTD exposure, cubic and monoclinic crystals increased, tetragonal crystals decreased, and the particle size increased. As the sintering temperature increased, the particle size increased, but not according to the sintering time. At all sintering times, the flexural strength of zirconia was over 800 MPa, which is the minimum flexural strength of a 4-unit or longer prosthesis as specified in the International Organization for Standardization (ISO) 6872. With LTD exposure, the increase in the flexural strength of zirconia was associated with the phase change from tetragonal to monoclinic.


The interaction of acetoxy-dimethylnitrosamine, a proximate metabolite of the carcinogenic amine, and bacteriophages R17 and T7.
The biological and physicochemical effects of reacting bacteriophages R17 and T7 with acetoxy-dimethylnitrosamine (ADMN) have been studied. The rate-determining step in the reactions appeared to be the loss of the acetoxy group by hydrolysis, the hydroxymethyl-methylnitrosamine generated decomposing rapidly to give a methyldiazonium ion and formaldehyde. In experiments with bacteriophage suspended in phosphate buffer the biological inactivation observed was the sum of the effects of the formaldehyde and of alkylation by the methylcarbonium ion produced from the diazonium ion. In experiments with bacteriophage suspended in Tris--HCl buffer the effects of formaldehyde were eliminated by its reaction with the buffer component. Alkylation by the carbonium ion produced unstable phosphotriesters in the bacteriophage RNA which on hydrolysis led to degradation of the molecule. In phosphate buffer the formaldehyde cross-linked the protein coat of the bacteriophage blocking the extraction of the RNA. Estimates of the mean lethal dose and of the extent of degradation of the RNA following reaction in Tris--HCl buffer were fairly close to those observed in experiments with N-methyl-N-nitrosourea (MNUA).