Epigenetic silencing of miR-125b is required for normal B-cell development.
Deregulation of several microRNAs (miRs) can influence critical developmental checkpoints during hematopoiesis as well as cell functions, eventually leading to the development of autoimmune disease or cancer. We found that miR-125b is expressed in bone marrow multipotent progenitors and myeloid cells but shut down in the B-cell lineage, and the gene encoding miR-125b lacked transcriptional activation markers in B cells. To understand the biological importance of the physiological silencing of miR-125b expression in B cells, we drove its expression in the B-cell lineage and found that dysregulated miR-125b expression impaired egress of immature B cells from the bone marrow to peripheral blood. Such impairment appeared to be mediated primarily by inhibited expression of the sphingosine-1-phosphate receptor 1 (S1PR1). Enforced expression of S1PR1 or clustered regularly interspaced short palindromic repeats/Cas9-mediated genome editing of the miR-125b targeting site in the S1PR1 3' untranslated region rescued the miR-125b-mediated defect in B-cell egress. In addition to impaired B-cell egress, miR-125b dysregulation initially reduced pre-B-cell output but later induced pre-B-cell lymphoma/leukemia in mice. Genetic deletion of IRF4 was found in miR-125b-induced B-cell cancer, but its role in oncogenic miR-125b-induced B-cell transformation is still unknown. Here, we further demonstrated an interaction of the effects of miR-125b and IRF4 in cancer induction by showing that miR125b-induced B-cell leukemia was greatly accelerated in IRF4 homozygous mutant mice. Thus, we conclude that physiological silencing of miR-125b is required for normal B-cell development and also acts as a mechanism of cancer suppression.


Culturally sensitive and culturally comprehensive care.
Nursing is essentially about caring for others (Leininger, 1988) and it is this emphasis on care that distinguishes nursing from other professions, most notably medicine, which are oriented towards cure. To achieve culturally sensitive care nurses need to develop a knowledge base which incorporates an awareness of their own culture, preferences and prejudices alongside specific information about ethnic groups.


Comparative study of a new Chrysosporium species with Histoplasma capsulatum.
The Chrysosporium state of a new ascomycete, Renispora flavissima (Gymnoascaceae), resembles Histoplasma capsulatum in its macroconidial morphology. It was discovered growing in bat guano, from which it was readily isolated by direct plating of diluted soil, but only rarely from mice inoculated with soil suspensions. The fungus was consistently reisolated from tissues of mice inoculated intravenously and intraperitoneally with conidial and mycelial suspensions from cultures of the fungus. Nevertheless, there is no evidence that this species is pathogenic. Cultures grew at 37 degrees C, but did not convert to a yeast form on agar media or within cultured mouse peritoneal macrophages. Although the hyphae and conidia of this fungus fluoresce when stained with H. capsulatum fluorescent antibodies, exoantigens of the fungus produce neither H nor M precipitin bands, thus differentiating it from H. capsulatum. Both H. capsulatum and the new Chrysosporium sp. demonstrate isozyme polymorphism, and isozymic differences have been discussed between the two species.


Antiviral activity of a synthesized shikonin ester against influenza A (H1N1) virus and insights into its mechanism.
This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism. MDCK and A549 cells were used to investigate influenza viral infection and the structure-activity relationship between PMM-034 and NA was evaluated by pharmacophore-based docking modeling. The production of viral protein was tested by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM-034 to 16μg/mL and this showed a selective index of 10mM. PMM-034 inhibited NA in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease in viral nucleocapsid protein mRNA was observed in infected cells after treatment with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding pocket of NA bound to PMM-034 in the docking model. Taken together, these results suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential anti-H1N1 drug.


Root starch accumulation in response to arbuscular mycorrhizal colonization differs among Lotus japonicus starch mutants.
Arbuscular mycorrhizal (AM) fungi are obligate symbionts dependent for completion of their life cycle on plant carbohydrates, which they trade for mineral nutrients. Plant colonization by AM fungi is therefore expected to induce profound changes in plant carbon metabolism. We have previously observed that on one hand starch accumulation increases in responses to pre-symbiotic fungal signals and on the other hand, it decreases in mycorrhizal Lotus japonicus roots (Gutjahr et al. in New Phytol 183:53-61, 2009). To examine the importance of starch metabolism for AM development, we took advantage of a novel series of Lotus japonicus mutants impaired either in starch degradation or in synthesis. Normal AM colonization in all mutants indicated that defects in starch metabolism do not affect AM development and that carbohydrates can be supplied to the AM fungus without a requirement for starch synthesis. Furthermore, our experiments allowed us to characterize root starch dynamics in detail and point to continued turnover of starch in the degradation mutants in the presence of mycorrhiza.


Half-cycle-pulse terahertz emission from an ultrafast laser plasma in a solid target.
Coherent far-IR radiation is observed upon the generation of dense laser-driven plasma in a solid copper target. The coherent radiation demonstrates a strong half-cycle-pulse nature with temporal dynamics as fast as 150 fs. Comparisons between the data and radiation models are discussed. This measurement demonstrates a new method of performing ultrafast laser-plasma diagnostics in solid targets.


Diagnosis and Management of a Hypersensitivity Reaction to Titanium-Containing Surgical Clips: A Case Report.
Although titanium allergies are not commonly diagnosed, they can present with a variety of conditions years after the implantation of titanium-containing medical devices. Furthermore, there are few options to effectively manage the long-term outcomes of these conditions. We present the case of a 41-year-old female who experienced neck swelling, pain, and difficulty swallowing 16 years after a right thyroid lobectomy for benign follicular adenoma, requiring the implantation of titanium-containing surgical clips in her neck. This was accompanied by an extensive symptomatic history, and the patient showed mild reactivity to nickel and titanium on a metal lymphocyte transformation test analysis. X-ray and computed tomography of the neck later confirmed the location of 18 surgical clips. The patient was diagnosed with a chronic immune disease including immune complex disease and mast cell activation-related symptoms. Symptoms were managed with low-dose naltrexone until the surgical clips were removed. Further research is needed to identify more accurate testing methods to diagnose titanium hypersensitivity. Alternative treatment methods should be explored to reduce disease burden and complications related to titanium-containing implants.


The Effect of Mammary Extracellular Matrix in Controlling Oral and Mammary Cancer Cells
Extracellular matrix (ECM) plays an important role in the normal physiology of tissues and progression to disease. Earlier studies and our external microarray data analysis indicated that mammary matrix from involuting tissue showed upregulation of genes involved in ECM remodeling. The present study examines the fate of mammary and oral cancer cells grown in the ECM from lactating mammary gland. Our findings show that non-tumorigenic cells, MCF10A and DOK cells did not proliferate but the tumorigenic and metastatic cells, SCC25 and MDA-MB-231, underwent apoptosis when grown on mammary ECM isolated from lactating mice. In addition, the cytokinesis marker, CEP55, was repressed in the oral and breast cancer cells. In contrast, these cells proliferated normally on mammary ECM isolated from mice undergoing involution. External microarray data analysis of mammary tissue further revealed over expression (~16 fold) of QSOX1 gene, which promotes cellular quiescence, in lactating mammary gland. A recent study has indicated that QSOX1 overexpression in breast cancer cells led to reduced proliferation and tumorigenic properties. This extracellular protein in mammary ECM may be responsible for reduced cellular proliferation. The present study has shown that ECM from lactating mammary gland can regulate signals to oral and breast cancer cells to halt cell division. This preliminary observation provided insights into the potential role of ECM factors present in lactating mammary gland as therapeutic targets to control cancer cell division. This preliminary study is an attempt to understand not only the requirement of ECM remodeling factors essential for the growth and survival of cancer cells but also the factors present in the lactation matrix that simultaneously halts cell division and selectively inhibits the growth of cancer cells.


[Inhibitory effect of oil emulsions on the oocyst infectiveness of Eimeria tenella].
Comparative studies were carried out on the inhibitory effect of some oleoemulsions on the acute course of an experimental coccidial infection caused by Eimeria tenella. Such effect was demonstrated with the oral application of sporulated oocysts both with the complete and incomplete Freund's adjuvant and with oleum ricini and oleum helianthi in combination. The results of histopathologic investigations showed that the two types of Freund's adjuvant inhibited the rapid and joint excysting of a large number of oocysts. Inhibited was the invasion of sporozoits in the epithelial cells of the mucous membrane and thus the acute course of the coccidial infection caused by Eimeria tenella.


Mapping axonal density and average diameter using non-monotonic time-dependent gradient-echo MRI.
White Matter (WM) microstructures, such as axonal density and average diameter, are crucial to the normal function of the Central Nervous System (CNS) as they are closely related with axonal conduction velocities. Conversely, disruptions of these microstructural features may result in severe neurological deficits, suggesting that their noninvasive mapping could be an important step towards diagnosing and following pathophysiology. Whereas diffusion based MRI methods have been proposed to map these features, they typically entail the application of powerful gradients, which are rarely available in the clinic, or extremely long acquisition schemes to extract information from parameter-intensive models. In this study, we suggest that simple and time-efficient multi-gradient-echo (MGE) MRI can be used to extract the axon density from susceptibility-driven non-monotonic decay in the time-dependent signal. We show, both theoretically and with simulations, that a non-monotonic signal decay will occur for multi-compartmental microstructures - such as axons and extra-axonal spaces, which were here used as a simple model for the microstructure - and that, for axons parallel to the main magnetic field, the axonal density can be extracted. We then experimentally demonstrate in ex-vivo rat spinal cords that its different tracts - characterized by different microstructures - can be clearly contrasted using the MGE-derived maps. When the quantitative results are compared against ground-truth histology, they reflect the axonal fraction (though with a bias, as evident from Bland-Altman analysis). As well, the extra-axonal fraction can be estimated. The results suggest that our model is oversimplified, yet at the same time evidencing a potential and usefulness of the approach to map underlying microstructures using a simple and time-efficient MRI sequence. We further show that a simple general-linear-model can predict the average axonal diameters from the four model parameters, and map these average axonal diameters in the spinal cords. While clearly further modelling and theoretical developments are necessary, we conclude that salient WM microstructural features can be extracted from simple, SNR-efficient multi-gradient echo MRI, and that this paves the way towards easier estimation of WM microstructure in vivo.


[Research on attributes of biopharmaceutics classification system for Chinese materia medica of baicalein in Gegen Qinlian Decoction environment].
For the effects of multi-component environment on the solubility and permeability of single components,and the problems of biopharmaceutical attribute classification of single components in the compound prescriptions environment,baicalein was used as the research object in this study to investigate the biopharmaceutic attributes of single-component and their traditional Chinese medicine( TCM) biopharmaceutic attributes in the multi-component environment of Gegen Qilian Decoction. Shaking flask method,intrinsic dissolution rate test and HPLC were used to determine solubility of baicalein. Markers specified by FDA were utilized as permeable boundary reference materials to verify the applicability of the single-pass intestinal perfusion method( SPIP),and the quantitative research on the permeability of baicalein was also conducted. It is concluded that baicalein could be categorized as BCS-Ⅱ drug based on its low solubility and high intestinal permeability values,and it may be categorized into CMMBCS-I in the multi-component environment of Gegen Qilian Decoction due to its poor solubility but enhanced solubility and permeability in compound environment. This study could provide verification ideas for clinical determination of the best human oral dose of baicalein,and provide the data basis for the study of biopharmaceutics classification system of Chinese materia medica( CMMBCS).


[Experimental study on long-term prevention effect of chitosan electrospun membrane on cerebrospinal fluid leakage].
To study the long-term prevention effect of self-developed chitosan electrospun membrane on cerebrospinal fluid leakage. Twenty-five healthy adult New Zealand rabbits were selected to prepare the bilateral dural defect (0.8 cem x 0.8 cm in size) via midline incision of head. Defect of the right was repaired with chitosan electrospun membrane as the experimental group; defect of the left was not repaired as the control group. At 2-16 weeks after operation, one rabbit was sacrificed for the general observation of inflammatory response surrounding bone window and absorption of chitosan electrospun membrane; at 3 and 6 weeks after operation, 5 rabbits were sacrificed for sampling to observe histological change and collagen expression by_HE and Masson staining, and to measure the expressions of epidermal growth factor receptor (EGFR) and basic fibroblast growth factor (bFGF) by immunohistochemical staining. No inflammatory reaction of swelling, exudation, and sppuration appeared in the skin and subcutaneous tissue after operation in 2 groups. There was no adhesion around the chitosan electrospun membrane, and new fiber membrane formed under the chitosan electrospun membrane in the experimental group; no cerebrospinal fluid leakage happened; the chitosan electrospun membrane was gradually degraded with time, and was completely absorbed at 16 weeks. There was uneven scar around the dural detect in control group. Histological observation showed less inflammatory cell infiltration in the experimental group, showing significant difference in the number of inflammatory cells compared with control group at 3, 6 weeks (P < 0.05); capillary, granulation tissue and collagen fiber massively proliferated; collagen fiber arranged in line, and there was a clear borderline between chitosan electrospurn membrane and adjacent collagen fiber. The immunohistochemical staining showed that there were high expressions of bFGF and EGFR in the experimental group, and low expressions of bFGF and EGFR in the control group. Chitosan electrospun membrane for dural defect of rabbit can effectively reconstruct the dura, and it has exact long-term prevention effect on cerebrospinal fluid leakage.


Relationships between problematic alcohol consumption and delinquent behaviour from adolescence to young adulthood.
Heavy episodic drinking (HED) has been associated with increased risk for short- and long-term injury and harms, such as violence and delinquent behaviour; however, the temporal relationship between the two remains unclear, particularly on transition to young adulthood. This study investigates transactional pathways between HED and delinquent behaviour from adolescence to emerging adulthood. Data were drawn from the Australian Temperament Project; a population-based longitudinal study that has followed the health and development of participants (and parents) across 30 years from birth in 1982. The analytic sample was 1650 participants and included five measurement waves spanning adolescence (3 waves: 13-18 years) and young adulthood (2 waves; 19-24 years). There was strong continuity across waves of both HED and delinquency, as well as across-time associations between them. Delinquent behaviour in adolescence was associated with up to twofold increases in the odds of HED at each subsequent adolescent wave. HED in the late teens was associated with over fourfold increases in the odds of persistent (two waves) HED in young adulthood. HED in the late teens was associated with increases in the odds of delinquent behaviour in young adulthood (over twofold for male and one and a half-fold for female participants). While delinquent behaviour predicts both future HED and future delinquent behaviour in adolescence, once young people reach the legal drinking age of 18 years, HED becomes a predictor of current and future delinquent behaviour and future HED, suggesting that increased access to alcohol increases the likelihood of young people engaging in delinquent behaviour. [Miller PG, Butler E, Richardson B, Staiger PK, Youssef GJ, Macdonald JA, Sanson A, Edwards B, Olsson CA. Relationships between problematic alcohol consumption and delinquent behaviour from adolescence to young adulthood. Drug Alcohol Rev 2016;35:317-325].


Toll-like receptor-4 in human and mouse colonic epithelium is developmentally regulated: a possible role in necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is an immature intestinal condition resulting in devastating intestinal inflammation due to unknown mechanisms. Evidence has suggested that intestinal maturation attenuates the severity of NEC and Toll-like receptor 4 (TLR4) has been suggested to play a critical role in its pathogenesis. We investigated whether maturational effects of TLR4 expression in immature colon might contribute to the development of NEC. TLR4 colonocyte expression was detected by immunofluorescence confocal microscopy. Interleukin-6 (IL-6) levels were assayed by an enzyme-linked immunosorbent assay (ELISA). TLR4 expression was high in fetal colonic epithelium in human and mouse, with earlier gestation having a higher surface/cytoplasm distribution. TLR4 remained high in mouse postnatal day 1 but the surface/cytoplasm distribution was reduced. TLR4 decreased in amount and then was expressed in crypts in the mature human and mouse colon. Hydrocortisone (HC) reduced the surface/cytoplasm distribution of TLR4 in human fetal colon. Elevated IL-6 levels in immature colon after lipopolysaccharide were attenuated by HC in human and mouse. Expression, localization, and signaling of TLR4 in colonic epithelium may be developmentally regulated. HC may accelerate the TLR developmental pathway change to an adult type, which may account for its impact on TLR4 signaling.


Clinical and histological features of secondary carcinomas in gastrointestinal tract biopsies.
Secondary carcinoma involving the gastrointestinal (GI) tract is an uncommon finding in biopsy specimens. The diagnosis can be challenging for tumours mimicking a primary carcinoma and when the clinical context is unknown. A multicentre retrospective study was performed to evaluate the clinical and histological features of a series of secondary carcinoma in GI biopsies. A total of 197 cases from 190 patients (median age = 67 years; 57% females) were reviewed. In 16% of patients, the primary carcinoma was unknown. Most lesions presented endoscopically as mucosal or submucosal masses (58%). In 13%, the endoscopy was non-suspicious for malignancy. The most common tumours were carcinomas of the breast (38%), kidney (13%), lung (12%), prostate (8%) and ovary (7%). The sites of involvement were the stomach (34%), colon (27%), rectum (18%), duodenum (13%), oesophagus (5%), jejunum (3%) and anus (0.5%). Histological patterns of infiltration were mucosal (76%), submucosal (41%), lymphatic (14%), and epithelial colonisation (8%). Submucosal infiltration was found significantly more frequently in carcinomas of the prostate (67%) and lung (62%), compared with carcinomas of the ovary (27%) and breast (23%). Histological obstructive changes were observed in 36% of all cases, with the highest rate in prostate carcinoma (53%) and the lowest rate in kidney carcinoma (8%). Awareness of the main clinical and histological patterns of secondary carcinomas in GI tract biopsies may help pathologists to raise the possibility of this uncommon diagnosis and confirm it with the judicious use of immunohistochemistry.


An Aberrant Microbiota is not Strongly Associated with Incidental Colonic Diverticulosis.
Colonic diverticula are protrusions of the mucosa through weak areas of the colonic musculature. The etiology of diverticulosis is poorly understood, but could be related to gut bacteria. Using mucosal biopsies from the sigmoid colon of 226 subjects with and 309 subjects without diverticula during first-time screening colonoscopy, we assessed whether individuals with incidental colonic diverticulosis have alternations in the adherent bacterial communities in the sigmoid colon. We found little evidence of substantial associations between the microbial community and diverticulosis among cases and controls. Comparisons of bacterial abundances across all taxonomic levels showed differences for phylum Proteobacteria (p = 0.038) and family Comamonadaceae (p = 0.035). The r-squared values measuring the strength of these associations were very weak, however, with values ~2%. There was a similarly small association between the abundance of each taxa and total diverticula counts. Cases with proximal only diverticula and distal only diverticula likewise showed little difference in overall microbiota profiles. This large study suggests little association between diverticula and the mucosal microbiota overall, or by diverticula number and location. We conclude that the mucosal adherent microbiota community composition is unlikely to play a substantial role in development of diverticulosis.


Overexpression of a novel chrysanthemum Cys2/His2-type zinc finger protein gene DgZFP3 confers drought tolerance in tobacco.
A drought stress-responsive Cys2/His2-type zinc finger protein gene DgZFP3 was previously isolated (Liu et al., Afr J Biotechnol 11:7781-7788, 2012b) from chrysanthemum. To assess roles of DgZFP3 in plant drought stress responses, we performed gain-of-function experiment. The DgZFP3-overexpression tobacco plants showed significant drought tolerance over the wild type (WT). The transgenic lines exhibited less accumulation of H2O2 under drought stress, more accumulation of proline and greater activities of peroxidase (POD) and superoxide dismutase than the WT under both control conditions and drought stress. In addition, there was greater up-regulation of the ROS-related enzyme genes (NtSOD and NtPOD) and stress-related genes (NtLEA5 and NtDREB) in transgenic lines under normal or drought conditons. Thus DgZFP3 probably plays a positive regulatory role in drought stress response and has the potential to be utilized in transgenic breeding to improve drought stress tolerance in plants.


[The immunofluorescent detection of phosphorylated receptors of the epidermal growth factor during their internalization in A-431 cells].
Phosphorylated receptors of the epidermal growth factor (EGF) were localized in the human epidermoid carcinoma cells using immunofluorescent staining with antibody to phosphotyrosine. The application of EGF at 4 degrees C was seen to induce a characteristic fluorescence of the cell margins, whereas no cell staining occurs in the absence of EGF. After a 1 hour incubation of cells at 37 degrees C, within which the internalized EGF receptor complexes are accumulated in the juxtanuclear compartment near the para-Golgi region, the staining with antiphosphotyrosine antibody reveals the receptors in this region. It is concluded that the internalized EGF-receptor complexes may remain in the phosphorylated state.


Effects of an attachment-based intervention on daily cortisol moderated by dopamine receptor D4: a randomized control trial on 1- to 3-year-olds screened for externalizing behavior.
The effect of the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) on daily cortisol production was tested in a randomized controlled trial with 130 families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior. Six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline were conducted with individual families at their homes. Children in the intervention group showed lower cortisol levels, with a moderating role of the dopamine receptor D4 (DRD4) VNTR exon III polymorphism. The VIPP-SD program proved to be effective in decreasing daily cortisol production in children with the DRD4 7-repeat allele, but not in children without the DRD4 7-repeat allele. Our findings indicate that children are differentially susceptible to intervention effects dependent on the presence of the 7-repeat DRD4 allele.


Outcome of Husband-to-Wife Kidney Transplantation With Mutual Children: Single Center Experience Using T Cell-Depleting Induction and Review of the Literature.
Few data on husband-to-wife transplantations with mutual children (H2W) exist in the current era. We investigated the outcome of H2W transplantations (n = 25) treated with T cell-depleting induction compared to women with prior pregnancies also receiving their first HLA-mismatched kidney transplant, but from a different donor source: (i) other living donor (n = 52) and (ii) deceased donor (n = 120). Seventy-four percent of the women had ≥2 pregnancies; median follow-up time was 5 years. Death-censored allograft survival was significantly lower in the H2W group compared to the other two groups (p = 0.03). Three of four graft losses in the H2W group were due to rejection. 5-year patient survival in the H2W group was high and similar compared to the other living donor group (100 vs. 98%; p = 0.28). The incidence of (sub)clinical antibody-mediated rejection was higher in the H2W group (36 vs. 20 vs. 18%) (p = 0.10). The frequency of infections was similar among the three groups. No immunological parameter was predictive for rejection or graft loss in H2W transplantations. In conclusion, H2W transplantation is a valuable option, but associated with a higher risk for allograft loss due to rejection despite T cell-depleting induction. Further research is required for better risk prediction on an individual patient level.


Steroids for chronic inflammatory demyelinating polyradiculoneuropathy: evidence base and clinical practice.
Evidence-based therapies for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consist of corticosteroids, intravenous immunglobulins (IVIg), and plasma exchange. Steroids represent the oldest treatment used historically. In countries where readily available and affordable, IVIg tends to be favored as first-line treatment. The reason for this preference, despite substantially higher costs, is the perception that IVIg is more efficacious and safer than corticosteroids. However, the unselected use of IVIg as a first-line treatment option in all cases of CIDP raises issues of cost-effectiveness in the long-term. Furthermore, serious although rare, particularly thromboembolic side effects may result from their use. Recent data from randomized trials suggest pulsed corticosteroids to have a higher potential in achieving therapy-free remission or longer remission-free periods compared with IVIg, as well as relatively low rates of serious side effects when given as pulsed intravenous infusions during short periods of time. These specific advantages suggest that pulsed steroids could in many cases be used, as the first, rather than second choice of treatment when initiating immunomodulation in CIDP, primarily in hopes of achieving a remission after the short-term use. This article reviews the evidence base for the use of corticosteroids in its various forms in CIDP and factors that may influence clinicians' choice between IVIg and pulsed steroid treatment. The issue of efficacy, relapse rate and time, and side effect profile are analyzed, and some aspects from the authors' experience are discussed in relation to the possibility of using the steroid option as first-line therapy in a large proportion of patients with CIDP.


Silencing of Soybean Raffinose Synthase Gene Reduced Raffinose Family Oligosaccharides and Increased True Metabolizable Energy of Poultry Feed.
Soybean [Glycine max (L.) Merr.] is the number one oil and protein crop in the United States, but the seed contains several anti-nutritional factors that are toxic to both humans and livestock. RNA interference technology has become an increasingly popular technique in gene silencing because it allows for both temporal and spatial targeting of specific genes. The objective of this research is to use RNA-mediated gene silencing to down-regulate the soybean gene raffinose synthase 2 (RS2), to reduce total raffinose content in mature seed. Raffinose is a trisaccharide that is indigestible to humans and monogastric animals, and as monogastric animals are the largest consumers of soy products, reducing raffinose would improve the nutritional quality of soybean. An RNAi construct targeting RS2 was designed, cloned, and transformed to the soybean genome via Agrobacterium-mediated transformation. Resulting plants were analyzed for the presence and number of copies of the transgene by PCR and Southern blot. The efficiency of mRNA silencing was confirmed by real-time quantitative PCR. Total raffinose content was determined by HPLC analysis. Transgenic plant lines were recovered that exhibited dramatically reduced levels of raffinose in mature seed, and these lines were further analyzed for other phenotypes such as development and yield. Additionally, a precision-fed rooster assay was conducted to measure the true metabolizable energy (TME) in full-fat soybean meal made from the wild-type or transgenic low-raffinose soybean lines. Transgenic low-raffinose soy had a measured TME of 2,703 kcal/kg, an increase as compared with 2,411 kcal/kg for wild-type. As low digestible energy is a major limiting factor in the percent of soybean meal that can be used in poultry diets, these results may substantiate the use of higher concentrations of low-raffinose, full-fat soy in formulated livestock diets.


Weekly administration of high-dose sodium ferric gluconate is safe and effective in peritoneal dialysis patients.
This report describes the safety and efficacy of high-dose sodium ferric gluconate in 18 peritoneal dialysis (PD) patients. Nine patients received low-dose (125 mg) and 9 patients received high-dose (250 mg) sodium ferric gluconate once per week for 8 or 4 weeks, respectively, followed by a maintenance dose once every 4 weeks. Patients in both groups had low iron saturation before treatment (hemoglobin [Hgb] < 11 g/dl, transferrin saturation [TSAT] approximately 20%, and serum ferritin < 250 ng/ml). After treatment, TSAT and ferritin significantly increased in both the low-dose (ferritin 465 +/- 292 ng/ml and TSAT 33.5 +/- 6.9%) and high-dose (ferritin 622 +/- 339 ng/ml and TSAT 35.0 +/- 25.7%) groups compared to baseline. Hemoglobin levels also increased in both groups, but this was not statistically significant. No adverse reactions or transferrin oversaturation with high-dose sodium ferric gluconate were observed. In conclusion, high-dose sodium ferric gluconate was safe, convenient, and effective in treating iron deficiency in PD patients.


About the contrast of δ' precipitates in bulk Al-Cu-Li alloys in reflection mode with a field-emission scanning electron microscope at low accelerating voltage.
Characterising the impact of lithium additions in the precipitation sequence in Al-Li-Cu alloys is important to control the strengthening of the final material. Since now, transmission electron microscopy (TEM) at high beam voltage has been the technique of choice to monitor the size and spatial distribution of δ' precipitates (Al3 Li). Here we report on the imaging of the δ' phase in such alloys using backscattered electrons (BSE) and low accelerating voltage in a high-resolution field-emission scanning electron microscope. By applying low-energy Ar+ ion milling to the surface after mechanical polishing (MP), the MP-induced corroded layers were efficiently removed and permitted the δ's to be visible with a limited impact on the observed microstructure. The resulting BSE contrast between the δ's and the Al matrix was compared with that obtained using Monte Carlo modelling. The artefacts possibly resulting from the sample preparation procedure were reviewed and discussed and permitted to confirm that these precipitates were effectively the metastable δ's. The method described in this report necessitates less intensive sample preparation than that required for TEM and provides a much larger field of view and an easily interpretable contrast compared to the transmission techniques.


Safety of caspofungin for treating invasive nasal sinus aspergillosis in a kidney transplant recipient.
Invasive fungal sinusitis is a rare but often fatal infection in immunocompromised patients. Aggressive antifungal treatment is mandatory, but is not without risk. Caspofungin, an antifungal agent that is a member of the echinocandin family, an inhibitor of glucan synthesis in the fungal wall, is active against Aspergillus and Candidae infections. Although it works on the fungal wall, it does not affect mammalian cells; hence, its toxicity is minimal. This report describes a case of invasive Aspergillus sinusitis in a kidney transplant recipient with diabetes mellitus. The infection involved the apex of the right orbit causing optic nerve compression. The patient was treated with transnasal endoscopic decompression of the optic nerve and intravenous AmBisome (liposomal amphotericin B) for 2 weeks without clinical improvement. The combination of caspofungin and AmBisome administered for another 2 weeks yielded partial improvement. The AmBisome had to be discontinued due to deterioration of renal and hepatic function, but the patient completed a further 7-week course of caspofungin alone. Retro-orbital biopsy confirmed a complete response to treatment; the patient's renal and hepatic function returned to normal. This case indicates that caspofungin is effective to treat invasive Aspergillus sinusitis in kidney transplant recipients. This agent is well tolerated and safe with respect to renal and hepatic function.


Considerations in recruiting underscreened women to focus groups on screening for cervical cancer.
This article describes recruitment activities and costs from two independently conducted studies that used similar, systematic approaches to recruiting two subgroups of underscreened women, Black women and Mexican women. The studies varied in number of recruiters, venues of recruitment, and region of the country. The ratio of women approached to women who were underscreened was 4:1 for Black women and 10:1 for Mexican women. Hysterectomy was a predominant reason for ineligibility among Black women but not Mexican women. In both studies, personal networks were the most productive method of identifying women. Flyers and organized community venues were least productive. The cost incurred for identifying a woman who was eligible for a focus group was 145 dollars for Black women and 59 dollars for Mexican women. Those planning research or program activities that include recruiting underscreened women either to focus groups or health services could benefit from this information.


Differences in Lip Support with and without Labial Flanges in a Maxillary Edentulous Population. Part 1: Objective Analysis.
To study the objective differences in lip support using common facial soft tissue markers, when evaluating patients wearing a maxillary denture with a labial flange in comparison to an experimental flangeless denture. A total of 31 maxillary edentulous patients who were esthetically satisfied with their existing maxillary denture were recruited in this clinical study. The maxillary denture was then duplicated in clear acrylic resin. Two standardized full-face digital photographs (frontal and profile) were made with the duplicate denture in the mouth. The labial flange of the duplicate denture was then removed from first premolar to first premolar region, to create the experimental flangeless denture. It was returned to the oral cavity, and 2 additional full-face digital photographs were made. The differences between these images were studied using 5 facial anatomic markers (subnasale, labrale superior, stomion, nasolabial angle, lip thickness). A paired sample t-test was used to compare differences in measurements for various anatomic markers using an alpha value of 0.05. For profile images, there were no statistically significant differences between photographs with and without a labial flange for anatomic markers- labrale superior and stomion (p < 0.05). There was a statistically significant difference for subnasale as well as the nasolabial angle but the magnitude of the difference was too small to be clinically significant (p < 0.05). For frontal images, there was no statistically significant difference in lip thickness between photographs with and without a labial flange. Additionally, there was no association between differences in measurements and patient-related factors such as gender and prior years of edentulism. Removal of a labial flange in a maxillary denture resulted in minimal and clinically insignificant anatomic differences in lip support between flange and flangeless dentures, when analyzed in frontal and profile images.


Mutation of TGFβ-RII eliminates NSAID cancer chemoprevention.
Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit anti-neoplastic (chemoprevention) activity for sporadic cancers and the hereditary cancer predisposition Lynch syndrome (LS/HNPCC). However, the mechanism of NSAID tumor suppression has remained enigmatic. Defects in the core mismatch repair (MMR) genes MSH2 and MLH1 are the principal drivers of LS/HNPCC. Previous work has demonstrated that the villin-Cre+/-Msh2flox/flox (VpC-Msh2) mouse is a reliable model for LS/HNPCC intestinal tumorigenesis, which is significantly suppressed by treatment with the NSAID aspirin (ASA) similar to human chemoprevention. Here we show that including a TGFβ receptor type-II (Tgfβ-RII) mutation in the VpC-Msh2 mouse (villin-Cre+/-Msh2flox/floxTgfβ-RIIflox/flox ) completely eliminates NSAID tumor suppression. These results provide strong genetic evidence that TGFβ signaling and/or effectors participate in NSAID-dependent anti-neoplastic processes and provide fresh avenues for understanding NSAID chemoprevention and resistance.


Two-Year Follow-Up Outcomes of Premature Infants Enrolled in the Phase I Trial of Mesenchymal Stem Cells Transplantation for Bronchopulmonary Dysplasia.
To determine the long-term safety and outcomes of mesenchymal stem cells (MSCs) for bronchopulmonary dysplasia in premature infants enrolled in a previous phase I clinical trial up to 2 years of corrected age (CA). We assessed serious adverse events, somatic growth, and respiratory and neurodevelopmental outcomes at visit 1 (4-6 months of CA), visit 2 (8-12 months of CA), and visit 3 (18-24 months of CA) in a prospective longitudinal follow-up study up to 2 years' CA of infants who received MSCs (MSC group). We compared these data with those from a historical case-matched comparison group. One of 9 infants in the MSC group died of Enterobacter cloacae sepsis at 6 months of CA, the remaining 8 infants survived without any transplantation-related adverse outcomes, including tumorigenicity. No infant in the MSC group was discharged with home supplemental oxygen compared with 22% in the comparison group. The average rehospitalization rate in the MSC group was 1.4/patient because of respiratory infections during 2 years of follow-up. The mean body weight of the MSC group at visit 3 was significantly higher compared with that of the comparison group. No infant in the MSC group was diagnosed with cerebral palsy, blindness, or developmental delay; in the comparison group, 1 infant was diagnosed with cerebral palsy and 1 with developmental delay. Intratracheal transplantation of MSCs in preterm infants appears to be safe, with no adverse respiratory, growth, and neurodevelopmental effects at 2 years' CA. ClinicalTrials.gov: NCT01632475.


Development of a comprehensive Blast-Related Auditory Injury Database (BRAID).
The Department of Defense Hearing Conservation Program provides specific guidance for service components to prevent occupational hearing loss; however, it does not specifically contend with the unique noise exposures observed in the theater of war, such as blasts and explosions. In order to examine the effects of blast injury on hearing sensitivity, we developed a large database composed of demographic, audiometric, point of injury, and medical outcome data, with the primary aim of developing a long-standing and integrated capability for the surveillance, assessment, and investigation of blast-related hearing outcomes. Methods used to develop the dataset are described. Encompassing more than 16,500 Navy and Marine Corps personnel, the Blast-Related Auditory Injury Database (BRAID) includes individuals with a blast-related injury and nonblast control subjects. Using baseline and postdeployment hearing threshold data, a retrospective analysis of the cohort revealed that the rate of hearing loss for the injured servicemembers was 39%. The BRAID will be useful for studies that assess hearing patterns following deployment-related injury, such as blast exposures, that facilitate exploration of health outcomes and whether they are predictive of audiometric disposition and that help establish hearing loss prevention strategies and program policies for affected military commands and servicemembers.


Icariin improves the sexual function of male mice through the PI3K/AKT/eNOS/NO signalling pathway.
We aimed to investigate the effect and mechanism of icariin on male sexual function. Forty-eight Crl:CD1(ICR) male mice were randomly divided into control, low-, medium- and high-dose icariin group (intragastric administration of 50, 100 and 200 mg/kg/d for 21 days). Mating experiment was then performed at a ratio of 1: 3 (male: female). The mating behaviours of male mice were recorded. The genital indexes and serum testosterone, nitric oxide (NO), hypothalamic dopamine (DA) and 5- hydroxy tryptophan (5-HT) concentrations were measured. The expression of endothelial nitric oxide (eNOS), phosphatidylinositol tallow alcohol 3-kinase (PI3K) and phosphorylated protein kinase (p-AKT) in penile tissue was detected by Western blot. All icariin groups exhibited shorter capture latency and ejaculation latency, increased number of capture and ejaculation, higher capture and ejaculation rate, and higher testicular and prostate indexes compared with controls (p < .001). These groups had higher serum testosterone and NO concentrations (p < .001), hypothalamic DA and 5-HT levels, and eNOS, PI3K and phosphorylated AKT expressions in penile tissue (p < .05). The effect of icariin was dose-dependently increased. Our study suggests that icariin improves the sexual function of male mice, which might be associated with the hypothalamic-pituitary-gonadal axis and the PI3K/AKT/eNOS/NO signalling pathway.


Stabilization of High Oxidation State Upconversion Nanoparticles by N-Heterocyclic Carbenes.
The stabilization of high oxidation state nanoparticles by N-heterocyclic carbenes is reported. Such nanoparticles represent an important subset in the field of nanoparticles, with different and more challenging requirements for suitable ligands compared to elemental metal nanoparticles. N-Heterocyclic carbene coated NaYF4 :Yb,Tm upconversion nanoparticles were synthesized by a ligand-exchange reaction from a well-defined precursor. This new photoactive material was characterized in detail and employed in the activation of photoresponsive molecules by low-intensity near-infrared light (λ=980 nm).


Acute prostatitis probably due to Listeria monocytogenes in an HIV-infected patient.
We report a unique case of acute bacterial prostatitis probably caused by Listeria monocytogenes in an HIV-infected patient. For the best of our knowledge, this is the first case reported of a patient with this association. Our case illustrates the protean clinical presentations that L. monocytogenes infections may adopt, particularly in immunocompromised patients.


Identification and characterization of COPIa- and COPIb-type vesicle classes associated with plant and algal Golgi.
Coat protein I (COPI) vesicles arise from Golgi cisternae and mediate the recycling of proteins from the Golgi back to the endoplasmic reticulum (ER) and the transport of Golgi resident proteins between cisternae. In vitro studies have produced evidence for two distinct types of COPI vesicles, but the in vivo sites of operation of these vesicles remain to be established. We have used a combination of electron tomography and immunolabeling techniques to examine Golgi stacks and associated vesicles in the cells of the scale-producing alga Scherffelia dubia and Arabidopsis preserved by high-pressure freezing/freeze-substitution methods. Five structurally distinct types of vesicles were distinguished. In Arabidopsis, COPI and COPII vesicle coat proteins as well as vesicle cargo molecules (mannosidase I and sialyltransferase-yellow fluorescent protein) were identified by immunogold labeling. In both organisms, the COPI-type vesicles were further characterized by a combination of six structural criteria: coat architecture, coat thickness, membrane structure, cargo staining, cisternal origin, and spatial distribution. Using this multiparameter structural approach, we can distinguish two types of COPI vesicles, COPIa and COPIb. COPIa vesicles bud exclusively from cis cisternae and occupy the space between cis cisternae and ER export sites, whereas the COPIb vesicles bud exclusively from medial- and trans-Golgi cisternae and are confined to the space around these latter cisternae. We conclude that COPIa vesicle-mediated recycling to the ER occurs only from cis cisternae, that retrograde transport of Golgi resident proteins by COPIb vesicles is limited to medial and trans cisternae, and that diffusion of periGolgi vesicles is restricted.


Reversed Doppler effect in photonic crystals.
Nonrelativistic reversed Doppler shifts have never been observed in nature and have only been speculated to occur in pathological systems with simultaneously negative effective permittivity and permeability. This Letter presents a different, new physical phenomenon that leads to a nonrelativistic reversed Doppler shift in light. It arises when light is reflected from a moving shock wave propagating through a photonic crystal. In addition to reflection of a single frequency, multiple discrete reflected frequencies or a 10 GHz periodic modulation can also be observed when a single carrier frequency of wavelength 1 microm is incident.


Shape and size control of nano dispersed Mg/Al layered double hydroxide.
Controlling the shape and size of the layered inorganic-organic hybrid particles is a challenge with conventional methods of synthesis. The co-precipitation method has been modified to synthesize Mg/Al Layered double hydroxide by controlling the particle growth using ultrasonic wave at the time of nucleation. In this project, magnesium and aluminum ions were considered as model systems with carbonate anion as intercalating agent. The resulting particles are compared with those of LDHs produced by conventional co-precipitation method at constant pH. Powder X-ray diffraction confirmed formation of the layered double hydroxide phases having crystallite size 19-20 nm in both 'a' and 'c' crystallographic directions. Transmission electron microscope and dynamic light scattering revealed nano disperse hexagonal platelets with narrow size distribution and average size was around 48 nm. The modified method reduces the particle size, increases the surface charge, narrows down the size distribution and also reduces the aspect ratio of the particles. Therefore, it is suggested that low amplitude ultrasonic wave prevents the aggregation of the nuclei, thus restricting the particle growth and results in uniform size particles.


[Urinalysis as a diagnostic tool in severe malaria].
Malaria accounts for a significant morbidity and mortality rate around the world, especially in communities with limited access to healthcare. Some clinical signs in urine, like haematuria, coluria and proteinuria, help for the early diagnosis of severe malaria cases.A narrative review was conducted by analyzing 91 publications on studies about severe malaria cases and the use of urinalysis.A urinalysis can detect metabolic disturbances and organ injury. Its diagnostic utility for frequent complications caused by malaria, such as hepatic injury, kidney dysfunction and hemolysis, has been confirmed by recent Colombian studies.This test is an easy-to-use tool in outpatient clinics and with hospitalized patients to promptly recognize complicated cases, allowing the timely identification of different lesions in patients with malaria, thus contributing to the reduction of severe morbidity and mortality.


Bradykinin is not involved in angiotensin converting enzyme modulation of ovarian steroidogenesis and prostaglandin production in frog Rana esculenta.
Angiotensin converting enzyme (ACE) was demonstrated to modulate the production of 17beta-estradiol, progesterone and prostaglandin E2 (PGE2) in frog ovary of Rana esculenta. However, the activity was not mediated by angiotensin II (Ang II). In an attempt to identify the peptide involved in the pathway modulated by ACE, bradykinin, another physiological substrate of ACE, was chosen and incubated in the presence of the membrane suspension purified from the frog ovary homogenate. The hydrolytic products were analysed by reverse-phase high-pressure liquid chromatography (HPLC) analysis and the results showed that bradykinin was metabolized by membrane suspension. The presence of the protease inhibitors in the incubation mixture indicated ACE and neutral endopeptidase as being responsible for the bradykinin hydrolysis. Frog ovary was incubated in vitro in the presence of bradykinin (10 microM), bradykinin receptor antagonist NPC 567 (1 mg mL-1), bradykinin fragment (1-7) (10 microM), ACE (2.5 mU mL-1), captopril (0.1 mM) and lisinopril (0.1 mM). The results showed no modulating activity by bradykinin on ovarian 17beta-estradiol and PGE2 production, thus demonstrating that it was not involved in the ACE-modulated pathway.


Protein systems for feeding ruminant livestock: a European assessment.
The metabolizable protein system for ruminants, published recently in the United Kingdom (2), was based upon earlier proposals (3, 4). The system includes a number of changes designed to represent the extent of protein degradation in the rumen and the synthesis of microbial protein as variable functions. The system also provides a more rational description of the energy available for microbial growth (fermentable metabolizable energy) by discounting the energy content of dietary lipids and fermentation end products (silages), which are considered to make a relatively insignificant contribution or none to microbial metabolism. The assessment of availability of undegraded dietary protein in the small intestine is revised also, and variable efficiencies of utilization of absorbed AA in relation to the nature of the synthetic process (e.g., meat and milk) are proposed. This paper considers these changes and assesses the adequacy of current laboratory techniques for determining the protein value of feedstuffs for ruminants. A number of conceptual and technical problems are identified, and ways of overcoming them are discussed. We conclude that such systems must be used in practice with guarded enthusiasm and suggest that mechanistic models, which provide a more appropriate representation of the biological processes, be encouraged as the basis of the next generation of feeding systems.


Effectiveness of disinfectant treatments for inactivating Piscirickettsia salmonis.
This short communication investigated in vitro differences between commercial disinfectants types (n = 36), doses of application, and time of action in the elimination of Piscirickettsia salmonis, the most important bacterium affecting farmed salmon in Chile. Seven different treatments were examined, including active and inactive chlorine dioxides, glutaraldehyde, hypochlorite disinfectants and detergents, peracetic acid, peroxides and other miscellaneous methods A 3 replicate set of each of the sample groups was stored at 20 °C and 95% relative humidity and retested after 1, 5 and 30 min with varying doses (low, recommended and high doses). Multiple comparison tests were performed for the mean log CFU/ml among different disinfectant types, dose (ppm) and time of exposure (minutes) on the reduction of P. salmonis. Overall, disinfection using peracetic acid, peroxides, and both active and inactive chlorine dioxides caused significantly higher reduction of >7.5 log CFU/ml in samples, compared to other tested sanitizers. The lowest reduction was obtained after disinfection with hypochlorite detergents. As expected, as doses and time of action increase, there was a significant reduction of the overall counts of P. salmonis. However, at lowest doses, only use of paracetic acids resulted in zero counts. Implementation of effective protocols, making use of adequate disinfectants, may enhance biosecurity, and ultimately, mitigate the impact of P. salmonis in farmed salmon.


In vitro Sertoli cell bioassay of follicle-stimulating hormone (FSH)-serum from different animal species alters the morphology of rat Sertoli cells without affecting their response to FSH.
Follicle-stimulating hormone (FSH) stimulates aromatase activity of immature rat Sertoli cells cultured in vitro in the presence of an androgen substrate, a phenomenon that can be used to measure FSH bioactivity. This paper analyzes the effects of sera from various animal species on both aromatase activity and morphological aspects of cultured rat Sertoli cells. Treatment of Sertoli cells with increasing concentrations of serum from humans, monkeys, rats, hamsters, and mice gave a dose-dependent stimulation of estradiol production parallel to the response obtained with FSH standard. Serum from these species and from rabbits also had a characteristic morphological effect on the cells, to produce a fibroblast-like aspect and clumping. This effect was dose-dependent, was increased by the addition of FSH, and was eliminated by heating the sera at 56 degrees for 30 min prior to incubation with the cells. Clumping did not interfere with the aromatase activity of Sertoli cells and did not cause the cellular response to deviate from parallelism with the standard curve. Heat treatment of FSH standard and serum samples did not significantly change the aromatase activity. FSH bioactivity could be measured accurately in intact and castrated monkeys. It is concluded that the Sertoli cell aromatase bioassay can be applied directly to the measurement of serum bioactive FSH in several animal species without any preliminary treatment of the serum samples.


Baseline C-reactive protein levels are predictive of treatment response to a neuroimmune modulator in individuals with an alcohol use disorder: a preliminary study.
Background: Inflammation is implicated in alcohol use disorder (AUD). Ibudilast, a neuroimmune modulator, shows promise for the treatment of AUD. Elevated inflammation, indicated by high levels of C-reactive protein (CRP), represents a possible subtype of AUD, which may be associated with treatment response to ibudilast.Objectives: The current study evaluated CRP as a predictor of treatment response to ibudilast; hypothesizing that ibudilast would be more effective at reducing drinking and alcohol cue-reactivity in individuals with higher CRP levels.Methods: This is a secondary analysis of a clinical trial of ibudilast for AUD, which found that ibudilast reduced heavy drinking in individuals with AUD. Fifty-one individuals were randomized to receive ibudilast (n = 24 [16 M/8F]) or placebo (n = 27 [18 M/9F]) for two weeks. Participants provided blood samples at baseline to assess CRP levels, completed daily assessments of alcohol use, and an fMRI alcohol cue-reactivity task at study mid-point. Models tested the effects of medication, CRP levels, and their interaction on drinks per drinking day and alcohol cue-reactivity.Results: There was a significant interaction between medication and CRP (F = 3.80, p = .03), such that the ibudilast high CRP group had fewer drinks per drinking day compared to the ibudilast low CRP group. CRP moderated the effect of medication on brain activation in a cluster extending from the left inferior frontal gyrus to the right-dorsal striatum (Z = 4.55, p < .001). This interaction was driven by attenuated cue-reactivity in the ibudilast high CRP group relative to the ibudilast low CRP and placebo high CRP groups.Conclusions: This study serves as an initial investigation into predictors of clinical response to ibudilast treatment and suggests that a baseline proinflammatory profile may enhance clinical efficacy.


Effect of various cytokine combinations on induction of non-MHC-restricted cytotoxicity.
Efforts were directed to achieve an increased lymphokine-activated non-MHC-restricted killing (LAK) activity greater than that induced by rIL-2 alone. Human peripheral blood (PB) and bone marrow (BM)-derived mononuclear cells (MC) were exposed in vitro to multiple cytokine combinations, including rIL-6, rIL-7, rIFN-alpha and rIFN-gamma in the presence of either suboptimal or optimal doses of rIL-2. Our results have shown that BMMC are a potential source for induction of increased LAK activity upon exposure to multiple cytokine combinations, whereas PBMC could not be successfully stimulated under the same conditions. Fifty-five to 62% of BM-derived samples stimulated with high dose rIL-2 + rIL-7 or rIL-2 + rIL-7 + rIL-6 + rIFN-gamma exhibited a higher degree of cytotoxicity than BM samples stimulated with rIL-2 alone. Exposure of PB-derived large granular lymphocytes (LGL) to various cytokine combinations led to increased proliferation after stimulation with suboptimal dose of rIL-2 in the presence of rIL-6 and rIL-7. This increase was not observed in induction of cytotoxicity. We suggest that BMMC activated by multiple cytokine combinations could play an active role in improving antitumor response in vivo by contributing to the control of minimal residual tumor cell growth, particularly post-BM transplantation.


Regeneration from different levels along the tail of the newt, Notophthalmus viridescens.
Some aspects of the influence of position on regeneration have been examined by comparing regeneration from different levels along the newt tail. Tails amputated such that either three-fourths one-half or one-fourth of the tail was removed pass through the same morphological and histological stages at the same times after amputation. In tails amputated at these three different levels, the rate of elongation of regenerates from more proximal levels is greater than that of regenerates from more distal levels. The total lengths of regenerates from different levels are proportional to the lengths of tail removed by amputation. Furthermore, the number of vertebrae formed in a tail regenerate is directly proportional to the number of vertebrae removed by amputation. When a tail blastema is transplanted to a more proximal level tail stump, intercalary regeneration between the stump and transplant occurs and the resulting regenerate has a complement of vertabrae appropriate to its new level along the tail. The results indicate that position along the appendage does not influence the developmental sequence of events of regeneration, but that it does influence the rate of growth and the structures to be replaced.


Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn.
The current standard of care in proton pump inhibitor failure is to double the proton pump inhibitor dose, despite limited therapeutic gain. Aims To determine the efficacy of adding acupuncture vs. doubling the proton pump inhibitor dose in gastro-oesophageal reflux disease patients who failed symptomatically on proton pump inhibitors once daily. Thirty patients with classic heartburn symptoms who continued to be symptomatic on standard-dose proton pump inhibitors were enrolled into the study. All participants underwent upper endoscopy while on proton pump inhibitors once daily. Subsequently, patients were randomized to either adding acupuncture to their proton pump inhibitor or doubling the proton pump inhibitor dose over a period of 4 weeks. Acupuncture was delivered twice a week by an expert. The two groups did not differ in demographic parameters. The acupuncture + proton pump inhibitor group demonstrated a significant decrease in the mean daytime heartburn, night-time heartburn and acid regurgitation scores at the end of treatment when compared with baseline, while the double-dose proton pump inhibitor group did not demonstrate a significant change in their clinical endpoints. Mean general health score was only significantly improved in the acupuncture + proton pump inhibitor group. Adding acupuncture is more effective than doubling the proton pump inhibitor dose in controlling gastro-oesophageal reflux disease-related symptoms in patients who failed standard-dose proton pump inhibitors.


The relation between cannabis use, dependence severity and white matter microstructure: A diffusion tensor imaging study.
Despite the significant societal and personal burden of cannabis use, the impact of long-term use and Cannabis Use Disorder (CUD) on white matter microstructure is still unclear. Previous studies show inconsistent findings, in part due to heterogeneity in methodology, variable severity of cannabis use, and potential confounding effects of other mental health issues and substance use. The goal of this diffusion tensor imaging (DTI) study was to compare whole-brain white matter microstructure between 39 near daily cannabis users and 28 controls closely matched on age, sex, alcohol use, cigarette use and mental health. Within the group of cannabis users, associations between white matter microstructure and recent cannabis use, dependence severity, and age of onset and duration of weekly use were investigated. White matter microstructure did not differ between cannabis users and controls and did not covary with recent cannabis use, dependence severity, or duration of use. Earlier onset of weekly cannabis use was related to lower fractional anisotropy (FA) in various sections of the right inferior longitudinal fasciculus and uncinate fasciculus. These findings suggest that long-term near-daily cannabis use does not necessarily affect white matter microstructure, but vulnerability may be higher during adolescence. These findings underscore the importance of sample composition and warrant further studies that investigate the moderating role of age of onset in the impact of cannabis on the brain.


[Infrainguinal bypass grafting in patients with end-stage renal disease and critical limb ischaemia: is it worthwhile?].
Patients with end-stage renal disease (ESRD) constitute an increasing proportion of patients undergoing infrainguinal bypass surgery for critical limb ischaemia (CLI). The aim of this retrospective study was to determine graft patency, healing of pedal lesions, limb salvage and survival following infrainguinal arterial reconstruction in this high-risk subset of patients. 34 patients with ESRD undergoing 37 bypass procedures for CLI (rest pain 2; tissue loss 35) were identified from the vascular registry. These included 13 femoropopliteal and 24 femorotibial bypasses with autogenous (67.6%) or prosthetic (32.4%) materials. The median age in this series was 62 years and 79% were diabetics. Using life-table analysis, the cumulative primary patency rate was 88% at 1 month and 81% at 2 years. The resulting limb salvage rate amounted to 94 and 86% at 1 month and 2 years, respectively. Healing of the pedal lesions was accomplished in only 50% of patients at 6 months. Toe lesions could be treated more successfully than forefoot and deep heel defects (p = 0.04). With a perioperative mortality of 3/37 cumulative survival rate declined to 21% at 2 years. Late mortality correlated significantly with a history of previous myocardial infarction or congestive heart failure (p = 0.001). Infrainguinal revascularisation can be performed in dialysis-dependent patients with acceptable patency and limb salvage rates. However, bypass grafting should be mainly reserved to patients without severe cardiac disease and to those without extensive tissue loss.


The Lactococcus lactis sex-factor aggregation gene cluA.
A gene, cluA, was cloned from the chromosomally located sex factor of Lactococcus lactis MG1363. Sequence analysis revealed significant homology with previously described aggregation proteins in Enterococcus and Streptococcus species. The possibility that cluA was an equivalent protein involved in cell aggregation between donor and recipient bacteria during lactococcal conjugation was confirmed by its expression under the control of a heterologous promoter in L. lactis. Analysis of the homology between the CluA protein and the related proteins of Enterococcus and Streptococcus allowed a common structure for these proteins to be postulated. This consisted of five domains. Functionally conserved domains I and V act respectively as a secretory leader and C-terminal membrane anchor. Domains II and IV are conserved at the amino acid level and probably have common structural roles whereas domain III is variable and may control binding specificity.


Study of the magnetic phase of Fe-Pt alloy nanoparticles.
High temperature solution phase decomposition of Fe(CO)5 and reduction of Pt(acac)2 in the presence of stabilizers of oleic acid and oleyl amine are employed to produce Fe(1-x)Pt(x) alloy nanoparticles. The Fe and Pt composition of the nanosized materials can be tuned by adjusting the molar ratio of Fe(CO)5 to Pt(acac)2, and the compositions ranging from Fe40Pt60 to Fe80Pt20 are obtained. This study is to investigate the influence of the composition on Curie temperature (Tc) of Fe(1-x)Pt(x) nanoparticles monitored by thermomagnetic analysis (TMA).


Histo and cyto-pathologic diagnoses at a rural hospital in Kenya.
Cancer has emerged as one of the common causes of morbidity and mortality in rural areas and as a major cause of premature deaths. To provide histo-pathology and cyto-pathology data in a rural district hospital and highlight on the common malignancies seen in a rural setting in Kenya. Prospective study. Histopathology Department, Machakos Provincial Hospital, Machakos district, Kenya. Two hundrend and sixty eight patients referred to Machakos laboratory for histopathology, fine needle aspirate or pap smear cyto-pathology were analysed. Staining with routine stains such Pap stain, Haeomatoxylin and Eosin was effective method of making a primary accurate and definitive histo-pathology and cyto-pathology diagnosis in a rural district hospital setting. Histo-pathology biopsies comprised 71.6% of the total slides seen. Pap smear cervical cytology comprised 13.8% while fine needle aspirate and post- mortem biopsies comprised 12.3%, 2.2% respectively. The commonest histo-pathology biopsies seen were breast comprising 24% of the total cases, followed by endometrium contributing 14.9%, then followed by skin 11.5%, lymph node 11.5%, cervical 11%, and gastrointestinal 6.3%. Most of pap smear cyto-pathology showed evidence of infection comprising 54% while fine needle aspirate infections and malignancy showed equal rate 24% of all cyto-pathology seen during this study. This is the first time histo-pathology and cyto-pathology data have been provided from a rural district hospital setting in Kenya. The malignant and pre-malignant pattern seen at Machakos General Hospital may be used to gain a broader picture of the common malignant conditions prevalent in any defined population in this country. This also serves as an important cancer epidemiological data in this region during the period of study.


Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial.
In sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA. Adults (≥18 years old) who were stable in HIV care and found to have prediabetes (IFG and/or IGT) and who were attending hospitals in Dar es Salaam, Tanzania, were randomised to receive sustained-release metformin, 2000 mg daily, or matching placebo between 4 November 2019 and 21 July 2020. Randomisation used permuted blocks. Allocation was concealed in the trial database and made visible only to the Chief Pharmacist after consent was taken. All participants, research and clinical staff remained blinded to the allocation. Participants were provided with information on diet and lifestyle and had access to various health information following the start of the coronavirus disease 2019 (COVID-19) pandemic. Participants were followed up for 12 months. The primary outcome measure was capillary blood glucose measured 2 h following a 75 g glucose load. Analyses were by intention-to-treat. In total, 364 participants (182 in each arm) were randomised to the metformin or placebo group. At enrolment, in the metformin and placebo arms, mean fasting glucose was 6.37 mmol/l (95% CI 6.23, 6.50) and 6.26 mmol/l (95% CI 6.15, 6.36), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 8.39 mmol/l (95% CI 8.22, 8.56) and 8.24 mmol/l (95% CI 8.07, 8.41), respectively. At the final assessment at 12 months, 145/182 (79.7%) individuals randomised to metformin compared with 158/182 (86.8%) randomised to placebo indicated that they had taken >95% of their medicines in the previous 28 days (p=0.068). At this visit, in the metformin and placebo arms, mean fasting glucose levels were 6.17 mmol/l (95% CI 6.03, 6.30) and 6.30 mmol/l (95% CI 6.18, 6.42), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 7.88 mmol/l (95% CI 7.65, 8.12) and 7.71 mmol/l (95% CI 7.49, 7.94), respectively. Using a linear mixed model controlling for respective baseline values, the mean difference between the metformin and placebo group (metformin-placebo) was -0.08 mmol/l (95% CI -0.37, 0.20) for fasting glucose and 0.20 mmol/l (95% CI -0.17, 0.58) for glucose levels 2 h post a 75 g glucose load. Weight was significantly lower in the metformin arm than in the placebo arm: using the linear mixed model adjusting for baseline values, the mean difference in weight was -1.47 kg (95% CI -2.58, -0.35). In total, 16/182 (8.8%) individuals had a serious adverse event (Grade 3 or Grade 4 in the Division of Acquired Immunodeficiency Syndrome [DAIDS] adverse event grading table) or died in the metformin arm compared with 18/182 (9.9%) in the placebo arm; these events were either unrelated to or unlikely to be related to the study drugs. Blood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV. The trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry ( www.isrctn.com/ ), registration number: ISCRTN76157257. This research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research.


Synthesis and luminescent properties of Eu(3+)-doped NaCaPO4 nano-particles under VUV-UV excitation.
A red emitting phosphor, Eu(3+)-doped NaCaPO4, has been prepared by the sol-gel method. X-ray powder diffraction (XRD) analyses confirmed the pure crystalline phase of NaCaPO4. The morphologies of the phosphor were investigated by scanning electron microscopy (SEM), which indicated that the phosphor had a good quality of surface crystallization. This phosphor had the grain sizes of around 500 nm with fairly narrow size distribution. The vacuum ultraviolet (VUV) synchrotron radiation spectroscopy technique was used to study the luminescence properties of this phosphor. The excitation spectra revealed that there is an efficient energy transfer from the phosphate host to Eu3+ ions. Upon excitation with VUV and UV radiation, the phosphor showed strong red emission around 618 nm corresponding to the forced electric dipole 5D0 --> 7F2 transition of Eu3+ ions. Defects and micro-structures that related to Eu3+ ions in the phosphate host are discussed.


All Inorganic Cesium Lead Iodide Perovskite Nanowires with Stabilized Cubic Phase at Room Temperature and Nanowire Array-Based Photodetectors.
Alluring optical and electronic properties have made organometallic halide perovskites attractive candidates for optoelectronics. Among all perovskite materials, inorganic CsPbX3 (X is halide) in black cubic phase has triggered enormous attention recently owing to its comparable photovoltaic performance and high stability as compared to organic and hybrid perovskites. However, cubic phase stabilization at room temperature for CsPbI3 still survives as a challenge. Herein we report all inorganic three-dimensional vertical CsPbI3 perovskite nanowires (NWs) synthesized inside anodic alumina membrane (AAM) by chemical vapor deposition (CVD) method. It was discovered that the as-grown NWs have stable cubic phase at room temperature. This significant improvement on phase stability can be attributed to the effective encapsulation of NWs by AAM and large specific area of these NWs. To demonstrate device application of these NWs, photodetectors based on these high density CsPbI3 NWs were fabricated demonstrating decent performance. Our discovery suggests a novel and practical approach to stabilize the cubic phase of CsPbI3 material, which will have broad applications for optoelectronics in the visible wavelength range.


Human infection with influenza virus A(H10N8) from live poultry markets, China, 2014.
Human infection with avian influenza virus A(H10N8) was initially reported in China in December 2013. We characterized H10N8 strains from a human patient and from poultry in live markets that infected persons had visited. Results of genome sequencing and virus characterization suggest that the virus strains that infected humans originated from these markets.


Large-Size Single-Crystal Oligothiophene-Based Monolayers for Field-Effect Transistors.
High structural quality of crystalline organic semiconductors is the basis of their superior electrical performance. Recent progress in quasi two-dimensional (2D) organic semiconductor films challenges bulk single crystals because both demonstrate competing charge-carrier mobilities. As the thinnest molecular semiconductors, monolayers offer numerous advantages such as unmatched flexibility and light transparency as well they are an excellent platform for sensing. Oligothiophene-based materials are among the most promising ones for light-emitting applications because of the combination of efficient luminescence and decent charge-carrier mobility. Here, we demonstrate single-crystal monolayers of unprecedented structural order grown from four alkyl-substituted thiophene and thiophene-phenylene oligomers. The monolayer crystals with lateral dimensions up to 3 mm were grown from the solution on substrates with various surface energies and roughness by drop or spin-casting with subsequent slow solvent evaporation. Our data indicate that 2D crystallization resulting in single-crystal monolayers occurs at the receding gas-solution-substrate contact line. The structural properties of the monolayers were studied by grazing-incidence X-ray diffraction/reflectivity, atomic force and differential interference contrast microscopies, and imaging spectroscopic ellipsometry. These highly ordered monolayers demonstrated an excellent performance in organic field-effect transistors approaching the best values reported for the thiophene or thiophene-phenylene oligomers. Our findings pave the way for efficient monolayer organic electronics highlighting the high potential of simple solution-processing techniques for the growth of large-size single-crystal monolayers with excellent structural order and electrical performance competing against bulk single crystals.


Intraductal papillary neoplasm of the bile duct : case report and review of the literature.
A variant of bile duct carcinoma, intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease mainly found in Eastern Asia which encompasses a spectrum of intraductal papillary growth occurring anywhere along the intrahepatic and/or extrahepatic biliary tree that carries a high potential for malignancy. We report the case of a patient with episodes of recurrent cholangitis that was diagnosed with IPNB, our clinical and diagnostic approach, the radiographic and endoscopic findings, the interventions used, while discussing the therapeutic options.


Achondroplasia With Congenital Onset Glaucoma, and Presumed Axenfeld-Rieger Anomaly.
We report the first case to our knowledge of a 1-week-old female infant with familial inherited achondroplasia associated with bilateral congenital onset glaucoma, posterior embryotoxon and iris hypoplasia suggestive of ocular Axenfeld-Rieger anomaly.


Cerebral asymmetry in the perception of overlapping brief time intervals?
The perception of duration, visually presented, has been studied depending on the visual half-field in which the light stimulations have been presented. The pair of intervals of equal duration, presented for comparison in the 200-1000 ms range, was studied in three different series, in each of which the beginning of the second interval followed accordingly: (a) 10 ms after the beginning of the first interval; (b) after 1/2 of the duration of the first interval; (c) the end of the first interval is at the same time the beginning of the second one. It has been established that two light stimuli of equal duration, presented consecutively in the left and right visual half-fields, are perceived as being different due to their temporal order, provided that the duration of the first interval has elapsed either prior to or at the moment of the onset of the second interval. The temporal order does not affect the subjective duration of overlapping light stimuli. It is possible to assume some kind of hemispheric asymmetry in the duration perception, provided some critical time has elapsed between the end of the first and the beginning of the second intervals. Such an asymmetry cannot be detected in the case of the overlapping intervals studied in the present work.


Perceived Parental Bonding, Early Maladaptive Schemas and Outcome in Schema Therapy of Cluster C Personality Problems.
The objective of this paper was to examine the relationships between perceived parental bonding, Early Maladaptive Schemas (Young et al., 2003), and outcome of schema therapy of Cluster C personality problems and whether the perceptions of parental bonding could be influenced by schema therapy. The sample consisted of 45 patients with panic disorder and/or agoraphobia and Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Cluster C personality traits who participated in an 11-week inpatient programme consisting of two phases; the first was a 5-week panic/agoraphobia-focused cognitive therapy, whereas the second phase was a personality-focused schema therapy. The patients were assessed at pre-treatment, mid-treatment and post-treatment and at 1-year follow-up. Opposite to our hypothesis, lower paternal care at pre-treatment was related to more reduction in Cluster C personality traits from pre-treatment to 1-year follow-up. Maternal protection was related to the schema domains of impaired autonomy and exaggerated standards. Overall schema severity and the schema emotional inhibition at pre-treatment were associated with less change in Cluster C traits. Perceived maternal care was reduced from pre-treatment to 1-year follow-up, and more reduction in maternal care was related to less reduction in Cluster C traits. Parental bonding failed to predict treatment outcome in the expected direction, but maternal protection was related to two of the schema domains. Overall schema severity and the particular schema emotional inhibition predicted outcome. Furthermore, perceived maternal care was reduced from before to after treatment. Future studies should examine these questions in larger samples of Cluster C patients receiving schema therapy of a longer duration. Most schemas within the impaired autonomy domain and the schema self-sacrifice seem to be related to low perceived maternal protection. Overall schema severity and the schema emotional inhibition predict a poorer outcome of schema therapy of Cluster C personality problems, and therapy should give priority to emotional inhibition when this schema is endorsed. Therapists should be aware that schema therapy carries the risk to lead to a more negative view of mother's care during upbringing and this risk is accentuated with less benefit of therapy.


Elastase levels during bile-induced pancreatitis in dogs determined by radioimmunoassay.
The changes in elastase levels were studied in the plasma before and after bile-induced pancreatitis. Although the anylase and lipase levels increased markedly, there was no significant increase in the plasma elastase levels, as measured by enzymatic assay. On the other hand, the elastase levels of the blood in the femoral and pancreatic veins as measured by radioimmunoassay, increased to about ten times above the control levels. Similarly, in pancreatitis, large amounts of elastase, determined by radioimmunoassay, was found in the ascitic fluid. At that time, no elastase activity could be determined in the ascitic fluid. In this study, it is suggested that circulating inhibitors interfere with the determination of elastase enzymatic activity but do not interfere with the radioimmunoassay of elastase.


Churg-Strauss syndrome.
Churg-Strauss syndrome (CSS), alternatively known as eosinophilic granulomatosis with polyangiitis (EGPA), was first described in 1951 by Churg and Strauss as a rare disease characterized by disseminated necrotizing vasculitis with extravascular granulomas occurring exclusively among patients with asthma and tissue eosinophilia. EGPA is classified as a small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs) and the hypereosinophilic syndromes (HESs) in which vessel inflammation and eosinophilic proliferation are thought to contribute to organ damage. Although still considered an idiopathic condition, EGPA is classically considered a Th2-mediated disease. Emerging clinical observations provide compelling evidence that ANCAs are primarily and directly involved in the pathogenesis of AASVs, although recent evidence implicates B cells and the humoral response as further contributors to EGPA pathogenesis. EGPA has traditionally been described as evolving through a prodromic phase characterized by asthma and rhino-sinusitis, an eosinophilic phase marked by peripheral eosinophilia and organ involvement, and a vasculitic phase with clinical manifestations due to small-vessel vasculitis. The American College of Rheumatology defined the classification criteria to distinguish the different types of vasculitides and identified six criteria for EGPA. When four or more of these criteria are met, vasculitis can be classified as EGPA. The French Vasculitis Study Group has identified five prognostic factors that make up the so-called five-factor score (FFS). Patients without poor prognosis factors (FFS=0) have better survival rates than patients with poor prognosis factors (FFS≥1). The treatment of patients with CSS must be tailored to individual patients according to the presence of poor prognostic factors. A combination of high-dose corticosteroids and cyclophosphamide is still the gold standard for the treatment of severe cases, but the use of biological agents such as rituximab or mepolizumab seems to be a promising therapeutic alternative.


M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan.
Mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) tumor suppressor- gene mutation is an early event in human hepatocellular carcinoma (HCC) formation in the United States, but its role in hepatocarcinogenesis in Japan is unclear. We therefore determined M6P/IGF2R mutation frequency in HCCs from patients who resided in the southern, central, and northern regions of Japan. Ten single nucleotide polymorphisms were used to identify HCCs and dysplastic liver nodules with M6P/IGF2R loss of heterozygosity. The retained allele in these tumors was also assessed for point mutations and deletions in the M6P/IGF2R ligand binding domains by direct sequencing of polymerase chain reaction (PCR) amplified DNA products. Fifty-eight percent (54 of 93) of the patients were heterozygous at the M6P/IGF2R locus, and 67% (43 of 64) of the HCCs and 75% (3 of 4) of the dysplastic nodules had loss of heterozygosity. The remaining allele in 21% of the HCCs contained either M6P/IGF2R missense mutations or deletions, whereas such mutations were not found in the dysplastic lesions. In conclusion, M6P/IGF2R is mutated in HCCs from throughout Japan with a frequency similar to that in the United States. Loss of heterozygosity in dysplastic liver nodules provides additional evidence that M6P/IGF2R haploid insufficiency is an early event in human hepatocarcinogenesis.


(Pro)renin Receptor in Kidney Development and Disease.
The renin-angiotensin system (RAS), a key regulator of the blood pressure and fluid/electrolyte homeostasis, also plays a critical role in kidney development. All the components of the RAS are expressed in the developing metanephros. Moreover, mutations in the genes encoding components of the RAS in mice or humans are associated with a broad spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). These forms of CAKUT include renal papillary hypoplasia, hydronephrosis, duplicated collecting system, renal tubular dysgenesis, renal vascular abnormalities, and aberrant glomerulogenesis. Emerging evidence indicates that (pro)renin receptor (PRR), a novel component of the RAS, is essential for proper kidney development and that aberrant PRR signaling is causally linked to cardiovascular and renal disease. This paper describes the role of the RAS in kidney development and highlights emerging insights into the cellular and molecular mechanisms by which the PRR may regulate this critical morphogenetic process.


Is hearing preservation useful in vestibular schwannoma surgery?
The goal of our study was to examine the usefulness of preserved hearing after unilateral vestibular schwannoma removal. The patients were assessed by clinical evaluation, preoperative and postoperative audiometric evaluation, operative findings, and postoperative functional results. Hearing was preserved in 47 of 119 patients. The postoperative hearing was better than 30 dB in 10 patients. During the follow-up, the hearing decreased 5 dB on average, and almost all of the decrement occurred during the first 6 months. Subjectively, the preserved hearing assisted in understanding of speech in 62% of the patients. Tinnitus did not interfere with understanding of speech. The age of the patients was the most significant factor associated with preserved hearing. Sixty-six percent of the patients with hearing preservation rated their preserved hearing as valuable. Neither tinnitus nor speech distortion reduced the appreciation for hearing preservation. We conclude that efforts to preserve hearing are worthwhile.


Lactobacillus fermentum F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice.
Hyperuricemia (HUA) is a systemic disease characterized by a disorder of purine metabolism and an abnormal increase in the serum level of uric acid (UA). Probiotics can exert potential therapeutic benefits against some metabolic diseases by regulating the intestinal microbiota. Lactobacillus fermentum F40-4 with UA-lowering activity of 87.40% was screened using purine as the target in vitro. The UA-lowering activity of L. fermentum F40-4 was further explored in a mouse model of HUA in vivo. L. fermentum F40-4 could downregulate serum levels of UA, blood urea nitrogen, creatinine, and xanthine oxidase by 40.84%, 11.61%, 57.66%, and 41.79%, respectively. L. fermentum F40-4 restored organ damage, and adjusted enzyme activity and transporter expression to promote the metabolic level of UA. In addition, L. fermentum F40-4 could reshape the gut microbiota and suppress inflammation to ameliorate HUA. An increment in intestinal UA excretion was documented. These findings suggest that L. fermentum F40-4 might serve as a potential probiotic for the prevention and treatment of HUA.


Memory order decomposition of symbolic sequences.
We introduce a general method for the study of memory in symbolic sequences based on higher-order Markov analysis. The Markov process that best represents a sequence is expressed as a mixture of matrices of minimal orders, enabling the definition of the so-called memory profile, which unambiguously reflects the true order of correlations. The method is validated by recovering the memory profiles of tunable synthetic sequences. Finally, we scan real data and showcase with practical examples how our protocol can be used to extract relevant stochastic properties of symbolic sequences.


Reasons for discontinuation of reversible contraceptive methods by women with epilepsy.
To report the reasons for discontinuation of contraceptive methods by women with epilepsy (WWE). These retrospective data come from a web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We determined the frequencies of contraceptive discontinuations and the reasons for discontinuation. We compared risk ratios for rates of discontinuation among contraceptive methods and categories. We used chi-square analysis to test the independence of discontinuation reasons among the various contraceptive methods and categories and when stratified by antiepileptic drug (AED) categories. Nine hundred fifty-nine of 2,393 (40.6%) individual, reversible contraceptive methods were discontinued. One-half (51.8%) of the WWE who discontinued a method discontinued at least two methods. Hormonal contraception was discontinued most often (553/1,091, 50.7%) with a risk ratio of 1.94 (1.54-2.45, p < 0.0001) compared to intrauterine devices (IUDs), the category that was discontinued the least (57/227, 25.1%). Among all individual methods, the contraceptive patch was stopped most often (79.7%) and the progestin-IUD was stopped the least (20.1%). The top three reasons for discontinuation among all methods were reliability concerns (13.9%), menstrual problems (13.5%), and increased seizures (8.6%). There were significant differences among discontinuation rates and reasons when stratified by AED category for hormonal contraception but not for any other contraceptive category. Contraception counseling for WWE should consider the special experience profiles that are unique to this special population on systemic hormonal contraception.


In Vitro Fertilization Outcomes With a Dual Trigger in Normoresponders in Antagonist Cycles.
Objectives To evaluate whether the dual trigger of ovulation with a gonadotropin-releasing hormone (GnRH) agonist and the standard dose of recombinant human chorionic gonadotropin (hCG) (dual trigger) is better than hCG alone in in vitro fertilization (IVF) cycles of patients who responded well to ovarian stimulation. Methods Between January 2013 and December 2021, 5593 antagonist cycles of patients were reviewed. This study included women who had an antral follicle count of 5 or more and exhibited a normoresponse to ovarian stimulation using the GnRH antagonist protocol, as determined by the follicular output rate (FORT). The primary outcome indicators consisted of the quantities of retrieved oocytes and mature oocytes. The secondary outcome markers included live birth rates, clinical pregnancy rates, and continued pregnancy rates. Results A total of 1244 normoresponder women who met the inclusion criteria were identified from the scanned files and subsequently enrolled in the GnRH antagonist protocol. A total of 383 cycles were observed in the group that was given the standard hCG trigger while 861 cycles were observed in the group that was given the dual trigger. The number of mature oocytes and top-quality embryos was significantly higher in the dual trigger group. The maturation rate in the hCG group was 74.8% while it was 76.9% in the dual trigger group (p=0.018). The dual trigger group exhibited an ongoing pregnancy rate of 37.6%, whereas the hCG group had a rate of 30.1% (p = 0.02). The dual trigger group exhibited a slightly higher live birth rate (34.3% vs 29.2%, p = 0.11), although this difference did not reach statistical significance. Conclusion Dual trigger of ovulation was superior to hCG alone in terms of the number of mature oocytes yielded, top quality of embryos, maturation rates, and ongoing pregnancy in IVF cycles of normoresponders having ovarian stimulation on the GnRH antagonist protocol.


Chronic pain in parturients with an accidental dural puncture: A case-controlled prospective observational study.
We set out to examine incidence of chronic headache and back pain in women with PDPH after accidental dural puncture during labor. Chronic headache, backache, and disability were assessed 18-24 months postpartum. Women with PDPH treated with epidural blood patch (PDPH-EBP) were identified and matched with women who had a PDPH without epidural blood patch (PDPH-no EBP), with women with uncomplicated epidural analgesia and with women without epidural analgesia. Our primary outcome was incidence of chronic headache and backache. Secondary outcome was the effect of epidural blood patch on chronic pain development. We used Chi-square or Fisher's exact test to calculate odds ratios. There was no statistically significant difference in demographic characteristics between groups. In the no epidural group, no women reported chronic headache and 2/116 (1.7%) reported chronic backache. In the uncomplicated epidural group, no women reported chronic headache and 7/116 (6.0%) reported chronic backache. In the PDPH-no EBP group, 9/56 (16.1%) women reported chronic headache and 10/56 (17.9%) reported chronic backache. In the PDPH-EBP group, 12/59 (20.3%) had chronic headache and 14/59 (23.7%) had chronic backache. No women in the no epidural or uncomplicated epidural group reported disability (chronic pain score of 3 or 4). High disability was reported by 8.9% of women in the PDPH-no EBP group and by 8.4% in the PDPH-EBP group. Women with PDPH had a high incidence of chronic headache, back pain, and disability. We did not find a statistically significant difference in chronic pain development between conservatively treated and EBP-treated patients.


Modifiable Risk Factors of Plantar Fasciitis in Non-Athletic Patients and Proposal of a New Objective Assessment System - RKISP.
Objective To determine the modifiable risk factors associated with severity of plantar fasciitis and to formulate an objective scoring system for indexing plantar fasciitis in the non-athletic population. Methods This was a prospective observational study. The main outcome measure was the association of a modifiable risk factor, which was measured with the Pearson coefficient (R-value) and the level of significance, which was kept as p < 0.05. Result In a sample size of 50 patients, the body mass index (BMI) and ill-cushioned shoes were found to be significantly associated with pain in plantar fasciitis. All the other risk factors were either non-modifiable or had no significant association. Conclusion Based on available data and further interpretation, an index was be formulated, named as Ranjeet-Kunal Index for Scoring Plantar fasciitis (RKISP), which can be successfully used for not only grading plantar fasciitis but also prognosticating the conservative management of the same, thus deciding the modality of treatment.