[Photoprotective mechanisms of human skin. Modulation by oligonucleotides].
There are at least two classic photoprotective DNA damage responses that can be elicited by UV exposure: induction of melanogenesis (tanning) and enhancement of DNA repair. Both mechanisms are mediated, at least in part, by the tumor-suppressor protein and transcription factor p53. Both of these responses can be induced in vitro as well as in vivo by small DNA fragments of specific sequences, without prior induction of actual DNA damage. The topical application of such fragments onto human skin might enhance photoprotection in human skin, as typically elicited by gradual sun exposure. The induction of photoprotection by this means, however, would not bear the mutagenic and carcinogenic risk of exposure to natural sunlight.


Clinical value of early assessment of hyperfibrinolysis by rotational thromboelastometry during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.
Coagulopathy may be the result of hyperfibrinolysis and could exacerbate bleeding following childbirth. Timely recognition of hyperfibrinolysis during the earliest stages of postpartum hemorrhage could identify women at risk of more severe blood loss who may benefit from targeted anti-fibrinolytic therapy. Rotational thromboelastometry (ROTEM® ) is a point-of-care test that could detect hyperfibrinolysis. The aim of this study was to evaluate whether early assessment of hyperfibrinolysis by ROTEM during postpartum hemorrhage could predict progression to severe postpartum hemorrhage. During a prospective cohort study in the Netherlands among women with postpartum hemorrhage (total blood loss at least 1000 ml within 24 h after childbirth) ROTEM measurements were performed following 800-1500 ml of blood loss. Hyperfibrinolysis was defined as an enzymatic fibrinolysis index (ROTEM EXTEM maximum clot lysis [ML] minus the ROTEM APTEM ML) above 15%. Severe postpartum hemorrhage was defined as a composite end point of total blood loss greater than 2000 ml, transfusion of four or more units of packed cells, and/or need for an invasive intervention. The predictive value of hyperfibrinolysis for progression to severe postpartum hemorrhage was assessed by area under the receiver operating curve (AUC) and positive and negative predictive values. ClinicalTrials.gov (NCT02149472). Of 390 women included, 82 (21%) had severe postpartum hemorrhage. Four (1%) women had thromboelastometric evidence of hyperfibrinolysis, of whom two developed severe postpartum hemorrhage. The AUC for enzymatic fibrinolysis index more than 15% for progression to severe postpartum hemorrhage was 0.47 (95% CI 0.40-0.54). Positive and negative predictive values for this index were 50.0% (95% CI 6.8-93.2) and 79.3% (95% CI 74.9-83.2), respectively. Thromboelastometric evidence of hyperfibrinolysis was rare in women with postpartum hemorrhage when assessed between 800 and 1500 ml of blood loss. The clinical predictive value of viscoelastometric point-of-care testing for hyperfibrinolysis for progression to severe postpartum hemorrhage during early postpartum hemorrhage is limited.


The VCP/p97 and YOD1 Proteins Have Different Substrate-dependent Activities in Endoplasmic Reticulum-associated Degradation (ERAD).
Endoplasmic reticulum-associated degradation (ERAD) is an essential quality control mechanism of the folding state of proteins in the secretory pathway that targets unfolded/misfolded polypeptides for proteasomal degradation. The cytosolic p97/valosin-containing protein is an essential ATPase for degradation of ERAD substrates. It has been considered necessary during retro-translocation to extract proteins from the endoplasmic reticulum that are otherwise supposed to accumulate in the endoplasmic reticulum lumen. The activity of the p97-associated deubiquitinylase YOD1 is also required for substrate disposal. We used the in vivo biotinylation retro-translocation assay in mammalian cells under conditions of impaired p97 or YOD1 activity to directly discriminate their requirements and diverse functions in ERAD. Using different ERAD substrates, we found that both proteins participate in two distinct retro-translocation steps. For CD4 and MHC-Iα, which are induced to degradation by the HIV-1 protein Vpu and by the CMV immunoevasins US2 and US11, respectively, p97 and YOD1 have a retro-translocation-triggering role. In contrast, for three other spontaneous ERAD model substrates (NS1, NHK-α1AT, and BST-2/Tetherin), p97 and YOD1 are required in the downstream events of substrate deglycosylation and proteasomal degradation.


The molecular origin and consequences of escape from miRNA regulation by HLA-C alleles.
Differential expression of human leukocyte antigen C (HLA-C) allotypes is mediated by the binding of a microRNA, miR-148a, to the 3' untranslated region of some, but not all, HLA-C alleles. The binding results in lower levels of HLA-C expression, which is associated with higher levels of HIV-1 viral load among infected individuals. The alternative set of HLA-C alleles has several substitutions in the miR-148a binding site that prevent binding and HLA-C downregulation; these high-expression alleles associate with control of HIV-1 viral load. We show that the common ancestor of all extant HLA-C alleles was suppressed by miR-148a. Substitutions that prevent miR-148a binding arose by a sequence exchange event between an HLA-C allele and an HLA-B (MIM 142830) allele of a B(∗)07-like lineage. The event occurred 3-5 million years ago, resulting in an HLA-C variant that escape from miR-148a downregulation. We present evidence suggesting that selection played a role in the successful spread of the HLA-C escape alleles, giving rise to 7 of the 14 extant HLA-C lineages. Notably, critical peptide and KIR binding residues of the escape variants have selectively converged to resemble the sequence of their inhibited counterparts, such that the inhibited and escape groupings differ primarily by their levels of expression.


Sex difference of barbiturate-protection in experimental cerebral ischemia in spontaneously hypertensive rats (SHR).
Survival time following bilateral carotid occlusion was significantly longer in spontaneously hypertensive rats (SHR) anesthetized with barbiturate than in those with ether. Under barbiturate anesthesia, female SHR survived longer (16.6 h) than did males (10.9 h), whereas such sex difference was not found in those with ether anesthesia. The present results indicate sex difference of barbiturate-protection in cerebral ischemia.


Oridonin attenuates LPS-induced early pulmonary fibrosis by regulating impaired autophagy, oxidative stress, inflammation and EMT.
Oridonin (Ori) possesses anti-inflammatory, antioxidant and antitumor properties. However, the effects of Ori on Lipopolysaccharide (LPS)-induced early pulmonary fibrosis remain unclear. We evaluated the protective effects of Ori on the mice model of pulmonary fibrosis. The BALB/C mice were given LPS (1 mg/kg) or Ori (20 mg/kg) according to experimental grouping. Then the left lung tissues were used for HE, immunohistochemical and Masson staining, and the right lung tissues were used for hydroxyproline measurement and western blot experiments. Bronchoalveolar lavage fluid was collected for Giemsa staining. The high levels of hydroxyproline induced by LPS were reduced by Ori treatment. Immunohistochemical staining and western blot analysis showed that Ori inhibited the increased levels of fibrosis-related proteins (α-smooth muscle actin, transforming growth factor-β, Collagen Ⅰ and phosphorylated-smad). Additionally, Ori treatment increased E-cadherin levels and decreased in Snail and Slug levels. Besides, Ori could suppress LPS-induced the infiltration of neutrophils and activation of the NLRP3 inflammasome. In addition, LPS caused the upregulation of NADPH oxidase 4 and exacerbated lung fibrosis. As the activator of NF-E2 related factor-2, Ori exerted protective effects in this animal model. Moreover, Ori reversed the LPS-triggered increases in Beclin-1, P62/sequestosome 1, autophagy related 3 and LC3. These findings suggested that Ori protected against LPS-induced early pulmonary fibrosis by inhibiting NLRP3-dependent inflammation, NADPH oxidase 4-dependent oxidative stress, the impaired autophagy and epithelial mesenchymal transformation.


[Dicrocoelium dendriticum egg in feces of 2 Somali boys in Denmark. Transitory elimination after arrival to Denmark].
A case of spurious infection with Dicrocoelium dendriticum in two Somali boys in Denmark, who had eaten sheep's liver, is described. The diagnosis was established by careful questioning regarding culinary habits.


Desmopressin effect on acetylsalicylic acid impaired platelet function.
The mechanism of DDAVP's shortening of acetylsalicylic acid (ASA) prolonged bleeding times was investigated. Sixteen healthy subjects received two dosages of ASA (100 mg) in 12 hours. Twenty four hours after the first ASA application and again after 32 hours DDAVP was administered intravenously (0.4 micrograms/kg). The trial was terminated after 48 hrs. In between, blood samples were drawn and analyzed for the in vivo bleeding time (Simplate time), in vitro bleeding test (IVBT, Thrombostat 4000), von Willebrand factor antigen (vWf:Ag), Ristocetin cofactor activity (vWf R:Co), plasma beta-thromboglobulin (beta-TG), platelet ATP/ADP, platelet aggregation (collagen, ADP, arachidonic acid), and plasma and platelet thromboxane levels. Simplate time (BT) and IVBT showed an excellent inverse correlation with vWf R:Co (r2 BT = 0.97 and r2 IVBT = 0.99, respectively) during the time when DDAVP was administered, suggesting the involvement of plasma vWF in DDAVP's shortening of the bleeding time. The involvement of plasma thromboxane in this mechanism could be excluded. In addition, DDAVP hampered platelet aggregation tests, possibly due to the inhibition of the release reaction (reduced beta-TG in plasma) by a direct interaction with platelets.


Experience with an adverse drug reaction reporting program in a neurology specialty clinic.
To describe an adverse drug reaction (ADR) reporting program that was developed in a university-affiliated neurology specialty clinic. Reportable ADRs were identified through 3 mechanisms: by clinicians through routine visits, by patients who were encouraged to follow up with the pharmacist in the clinic, and by the pharmacist who contacted high-risk patients. Patient demographics, the suspected drug(s), elements to define probability, and outcomes were documented, collated, and analyzed for trends and opportunities for continuous quality-improvement efforts. Information was shared with clinic administrators and clinicians. Serious ADRs were reported to the Food and Drug Administration. The experience during a 1-year period, during which 40 ADRs were reported, is described. Medications by frequency of report and types of reactions are reported. None of the ADRs required admission to the hospital. Pharmacy personnel reported the majority of ADRs (92.5%). This program is successfully incorporated within daily practice and is an integral part of quality-improvement efforts.


Vagus nerve stimulation: An update on a novel treatment for treatment-resistant depression.
In this review, we provide an overview of essential clinical trials examining the effect of vagal nerve stimulation (VNS) in treatment-resistant depression (TRD), the applicable neuroanatomy of the vagus nerve, and the proposed mechanism of action (MOA) of VNS in TRD. Vagal nerve stimulation (VNS) is currently the only FDA-approved neurostimulation treatment for severe treatment-resistant depression (TRD). The implanted VNS device sends electrical impulses to the left cervical vagus nerve, resulting in stimulation of afferent vagal brainstem pathways known to be associated with mood regulation. Within the last decade, several clinical trials have attempted to further elucidate this effect specifically in TRD. Early clinical trials including the D01, D02, and D03 trials showed promising evidence of the antidepressant efficacy and durability of VNS as a treatment for TRD. Later trials comparing VNS and treatment-as-usual (TAU) resulted in similar findings regarding antidepressant efficacy and durability. VNS was additionally found to be beneficial in improving quality of life and suicidality among unipolar TRD patients and depression among bipolar TRD patients. Ongoing and future studies such as the RECOVER trial continue to investigate the psychiatric benefits of VNS within the TRD population. Although the MOA of VNS in TRD is still not fully understood, recent brain imaging studies and animal studies have proven instrumental in addressing this knowledge gap.


Establishment and Characterization of Orthotopic Mouse Models for Human Uveal Melanoma Hepatic Colonization.
Uveal melanoma (UM) is a rare type of melanoma, although it is the most common primary ocular malignant tumor in adults. Nearly one-half the patients with primary UM subsequently develop systemic metastasis, preferentially to the liver. Currently, no treatment is effective for UM hepatic metastasis, and the prognosis is universally poor. The main challenge in designing a treatment strategy for UM hepatic metastasis is the lack of suitable animal models. We developed two orthotopic mouse models for human UM hepatic metastases: direct hepatic implantation model (intrahepatic dissemination model) and splenic-implantation model (hematogenous dissemination model) and investigated the tumorgenesis in the liver. A human UM cell line, established from a hepatic metastasis and nonobese diabetic severe combined immunodeficient γ mice, were used for development of in vivo tumor models. In the direct hepatic implantation model, a localized tumor developed in the liver in all cases and intrahepatic dissemination was subsequently seen in about one-half of cases. However, in the splenic implantation model, multiple hepatic metastases were observed after splenic implantation. Hepatic tumors subsequently seeded intra-abdominal metastasis; however, lung metastases were not seen. These findings are consistent with those observed in human UM hepatic metastases. These orthotopic mouse models offer useful tools to investigate the biological behavior of human UM cells in the liver.


BFP protein expression in transfected embryonic stem cells.
Cultured mouse embryonic stem cells can be transfected with a reporter gene encoding blue fluorescent protein BFP and regulated by drosophila heat shock protein 70 promoter. This gene is activated after heating and synthesizes matrix RNA. Blue protein is synthesized under these conditions. The system for transfection of stem cells allows us to activate automatically the corresponding transgenes.


Influence of laminin on the responsiveness of early chick embryo neural tube neurons to nerve growth factor.
Dissociated neurons from the neural tube containing the trigeminal motor nucleus from early chick embryos were cultured on laminin or collagen-polyornithine substrates, with and without nerve growth factor (NGF). Control cultures were grown in similar conditions with cytochrome-C. It was found that neuronal survival was not affected by NGF or cytochrome-C, but it was enhanced by laminin. The expression of neuritic processes, however, was significantly enhanced in the presence of NGF on both laminin and collagen-polyornithine surfaces, with the greatest number of neurons producing processes seen in the laminin-plus-NGF group. The length of processes was similarly enhanced by laminin and by NGF. Cytochrome-C did not influence any of these measures. The results indicate that while laminin potentiates the NGF effect on these early neuronal populations, NGF in conjunction with other substrata can have similar, though less dramatic, effects. These results, together with prior evidence of NGF receptors and specific NGF retrograde transport, suggest that this growth factor may play a significant role in the normal ontogeny of early motoneuron populations.


"Eritadenine as a regulator of anxiety Disorders: An experimental and docking Approach".
Uncertainty persists regarding the specific chemical causal factors and their corresponding behavioral effects in anxiety disorders. Commonly employed first-line treatments for anxiety target G protein-coupled receptors (GPCRs), including inhibitors of monoaminergic systems. Alternatively, emerging natural bioactive strategies offer potential for mitigating adverse effects. Recent investigations have implicated adenosine in anxiety-triggering mechanisms, while eritadenine, an adenosine analog derived from Shiitake mushroom, has displayed promising attributes. This study explores eritadenine's potential as a bioactive substance for anxiety disorders in mice, employing behavioral tests, pentobarbital-sleep induction, and molecular docking. Behavioral test results reveal a pronounced anxiolytic and sedative-hypnotic pharmacological effect of eritadenine. Our findings suggest that eritadenine may modulate locomotor functions mediated by adenosine receptors, with a stronger affinity for binding to A2AAR over A1AR, thus eliciting these effects.


Simple methodology for ensuring the precision of measuring radioactivity at low concentrations in very small tissues using quantitative whole-body autoradiography.
Quantitative whole-body autoradiography (QWBA) is largely used to evaluate tissue distribution of small molecule drugs. In QWBA, radioactivity is measured as the intensity obtained from the autoradiogram. It is known that lower intensity per a region of interest (ROI) or smaller size of ROI increases the variability of intensity. In fact, as some tissues are very small (e.g., the choroidea), ensuring reliability on the intensity for measuring radioactivity in these tissues is difficult in case of under- or over-estimation of radioactivity concentration owing to their variation of low radioactivity intensity of ROI. We thus analyzed the relationships between the size, intensity, and precision of ROI to determine the statistically significant lower limit of quantification (LLOQ) in very small tissues. To investigate the difference in correlation between the radiation source (commercial planar radiation standard [com-ST] and self-made radiation standard [self-ST] consisting of radioactive compounds and matrices), apparatus, or setting environment of the apparatus, correlation analysis was conducted under various conditions. Our results revealed that LLOQ can be calculated by simply using the correlation equation because a common relationship was observed between self-ST, which is used in QWBA, and com-ST. This methodology was thus considered valuable for ensuring LLOQ determination in QWBA.


Sequence of the dengue-1 virus genome in the region encoding the three structural proteins and the major nonstructural protein NS1.
Sequence results are presented for a 3745-nucleotide region at the 5' end of the dengue type-1 virus (DEN-1) genome. The strain characterized is a Western Pacific isolate from Nauru Island. The sequenced region contains the beginning of a continuous open reading frame which specifies the capsid (C), membrane (M), and envelope (E) structural proteins and the nonstructural protein NS1. The sequences are compared with corresponding segments for seven other flaviviruses, including two of the three remaining dengue serotypes, DEN-2 and DEN-4. The results show the DEN-1 genome size and organization to be similar to those of other characterized flaviviruses and that major features of the individual proteins are conserved. It is of special interest that comparisons of the E glycoprotein sequences between the dengue serotypes (DEN-1, -2, -4) reveal only moderately greater sequence relatedness (63-68%) than occurs in comparisons of DEN-1 with five other flaviviruses (46-54%). For the other structural proteins, C and M, the relatedness values are 59-74% for comparisons between DEN-1 and the other dengue serotypes and 31-45% for comparisons between DEN-1 and the five other flaviviruses.


Dysphagia at 1 Year is Associated With Mean Dose to the Inferior Section of the Brain Stem.
Dysphagia is a common toxicity after head and neck (HN) radiation therapy that negatively affects quality of life. We explored the relationship between radiation therapy dose to normal HN structures and dysphagia 1 year after treatment using image-based datamining (IBDM), a voxel-based analysis technique. We used data from 104 patients with oropharyngeal cancer treated with definitive (chemo)radiation therapy. Swallow function was assessed pretreatment and 1 year posttreatment using 3 validated measures: MD Anderson Dysphagia Inventory (MDADI), performance status scale for normalcy of diet (PSS-HN), and water swallowing test (WST). For IBDM, we spatially normalized all patients' planning dose matrices to 3 reference anatomies. Regions where the dose was associated with dysphagia measures at 1 year were found by performing voxel-wise statistics and permutation testing. Clinical factors, treatment variables, and pretreatment measures were used in multivariable analysis to predict each dysphagia measure at 1 year. Clinical baseline models were found using backward stepwise selection. Improvement in model discrimination after adding the mean dose to the identified region was quantified using the Akaike information criterion. We also compared the prediction performance of the identified region with a well-established association: mean doses to the pharyngeal constrictor muscles. IBDM revealed highly significant associations between dose to distinct regions and the 3 outcomes. These regions overlapped around the inferior section of the brain stem. All clinical models were significantly improved by including mean dose to the overlap region (P ≤ .006). Including pharyngeal dosimetry significantly improved WST (P = .04) but not PSS-HN or MDADI (P ≥ .06). In this hypothesis-generating study, we found that mean dose to the inferior section of the brain stem is strongly associated with dysphagia 1 year posttreatment. The identified region includes the swallowing centers in the medulla oblongata, providing a possible mechanistic explanation. Further work including validation in an independent cohort is required.


Mononuclear macrophage (M-CFC) colony formation in semisolid media in the absence of exogenous GM-CSF.
Human fetal bone marrow (FBM) cells were examined for the ability to form colonies in the absence of exogenous colony-stimulating factor (CSF) in double layer agar, methylcellulose (MC), and in agar-MC (agar underlayer, MC overlayer) culture systems. Without exogenous CSF, macrophage colonies (M-CFC) were formed in a combined culture of agar and MC. Aggregates of 5-40 cells were observed on day 7. Gradually, large compact colonies which survived for 10-12 weeks of cultivation, were formed. They were composed of mononuclear monocytes and multinucleated cells. M-CFC progenitors were nonadherent, but their progeny became adherent during differentiation within the colony. Colony formation was cell-dose-dependent. Depletion of monocytes increased the number of colonies in agar-MC cultures and stimulated the development of some macrophage colonies in MC. Survival of monocyte progenitors was not dependent on CSF. Neither was their proliferation nor partial differentiation in agar-MC cultures. CSF increased M-CFC colony efficiency, however, if it was present when cultures were initiated. Addition of CSF to M-CFC growing for 2-5 weeks in CSF-deprived medium stimulated monocytes proliferation and transformation into macrophages. Epithelioid cells, an increase in the number of giant multinucleated cells, and granulocyte multiplication were also observed. The absolute dependence of macrophage colony formation on CSF described by others might be a result of inadequate culture conditions due to agar rather than an intrinsic physiological requirement.


Efficient production of polymer-grade L-lactic acid from corn stover hydrolyzate by thermophilic Bacillus sp. strain XZL4.
Lactic acid has been identified as one of the top 30 potential building-block chemicals from biomass. Therefore, the search for cheap raw materials is an objective to reduce the production costs. Efficient polymer-grade L-lactic acid production was achieved in this report by a thermophilic strain Bacillus sp. XZL4 using corn stover hydrolyzate as sole carbon source. High L-lactic acid concentration (81.0 g L(-1)) was obtained from 162.5 g L(-1) concentrated corn stover hydrolyzate (total reducing sugar of 83.0 g L(-1)) with a volumetric productivity of 1.86 g L(-1) h(-1) (0-36 h) and a product yield of 0.98 g g(-1) total reducing sugars. This is the highest L-lactic acid concentration and yield reported from corn stover hydrolyzate. And the high optical purity of L-lactic acid obtained in this study also indicated that Bacillus sp. XZL4 is a promising polymer-grade L-lactic-acid producer from cellulosic biomass.


Six-year disease-free survival of a patient with metastatic eyelid squamous cell carcinoma and colon adenocarcinoma after repeated postoperative adoptive immunotherapy.
A 74-year-old male was affected concurrently with squamous cell carcinoma of the left eyelid and adenocarcinoma of the colon, both with lymph node metastasis. He underwent exenteration of the left orbit with left modified radical neck dissection and subsequently resection of the transverse colon with regional lymph node dissection. The patient has been treated by an adoptive immunotherapy as a sole postoperative modality without receiving any chemotherapeutic agents causing immunosuppression. For the adoptive immunotherapy, autologous peripheral blood lymphocytes were activated with an immobilized anti-CD3 antibody and IL-2 for 14 days (the CD3-AT cells). The infusion with 1.38 x 10(10) CD3-AT cells has been repeated 150 times in total at the time of writing. Neither recurrence nor additional metastasis has been detected for 6 years after surgery.


A Systematic Review of Youth and Teen Mental Health First Aid: Improving Adolescent Mental Health.
Adolescent mental illness often goes undetected. Youth and teen Mental Health First Aid (MHFA) are variations of adult MHFA that aims to help adults and adolescents recognize the signs and provide help where appropriate. We conducted a systematic review to summarize the current evidence for youth and teen MHFA, providing direction for future training and research. A systematic search was performed on September 12, 2020 on PubMed, Embase, PsycINFO, ERIC, and Cochrane using keywords related to teen or youth MHFA, adolescents, and mental health. A narrative synthesis was then carried out. Of the 695 articles identified, 14 studies were included. All studies were from the U.S. and Australia. All studies demonstrated significant improvements in knowledge, recognition, stigmatizing attitudes, confidence, helping intentions, and helping behavior in both adult and youth participants. Improvement in knowledge and confidence was most reported, and improvement in helping behavior was the least reported. There is encouraging evidence of long-term benefits after the training. More studies need to be conducted in non-Western countries, high-risk populations, and different professional settings. Future interventions could also consider different modes of learning, longer-term follow-up, and the measurement of outcomes that evaluate the quality of helping behavior.


Spinal cord injury repair by implantation of structured hyaluronic acid scaffold with PLGA microspheres in the rat.
In order to create an optimal microenvironment for neural regeneration in the lesion area after spinal cord injury (SCI), we fabricated a novel scaffold composed of a hyaluronic acid (HA) hydrogel with a longitudinal multi-tubular conformation. The scaffold was modified by binding with an anti-Nogo receptor antibody (antiNgR) and mixed further with poly(lactic-co-glycolic acid) (PLGA) microspheres containing brain-derived neurotrophic factor and vascular endothelial growth factor (HA+PLGA). In the rat, after implantation of this composite into an injured area created by a dorsal hemisection at T9-10 of the spinal cord, favorable effects were seen with regard to the promotion of spinal repair, including excellent integration of the implants with host tissue, inhibition of inflammation, and gliosis. In particular, large numbers of new blood vessels and regenerated nerve fibers were found within and around the implants. Simultaneously, the implanted rats exhibited improved locomotor recovery. Thus, this novel composite material might provide a suitable microenvironment for neural regeneration following SCI.


Preserving dignity in the young hospitalized child.
Bodily intrusion and exposure are common experiences for hospitalized children. Placing children in such compromising situations can have a significant impact on their self-perception. To recognize pediatric patients' inherent powerlessness in the hospital setting and suggest strategies to overcome it. Published literature and author's clinical experiences. Nurses have a key role in ensuring that the psychosocial issues of privacy, modesty, and self-esteem are recognized, respected, and incorporated appropriately into their clinical practice when caring for hospitalized children.


Monomorphic platinum octapod and tripod nanocrystals synthesized by an iron nitrate modified polyol process.
Monomorphic Pt octapod and tripod nanocrystals have been successfully synthesized by an iron nitrate modified polyol process, in which iron nitrate has been proven to be vitally important for slowing down the reduction rate of Pt precursors.


The Most Interesting Enzyme in the World.
Ribonucleotide reductases of the class I family are α2β2 tetramers. Like all RNRs they are subject to allosteric control mechanisms affecting activity and specificity. In this issue of Structure, Johansson et al. (2016) present a structural analysis of an unusual mode of activity site regulation.


Bromocriptine restores angiotensin II response in pituitary hyperplasia.
In estrogen-induced pituitary hyperplasia AII-evoked prolactin release is decreased and the octapeptide does not generate a spike elevation in [Ca(2+)](i) in vitro. We studied whether or not bromocriptine could restore AII response in diethylstilbestrol treated rats. Co-administration of bromocriptine resulted in involution of pituitary size and lowering of serum prolactin. In vitro, prolactin release per cell was reduced in the hyperplastic group, and levels were not significantly increased by in vivo bromocriptine treatment. Immunocytochemical analysis revealed that hyperplastic pituitaries contained fewer prolactin granules than control pituitaries, and that bromocriptine, did not increase prolactin storage. Nevertheless, in this group, prolactin response to AII increased, and AII evoked a consistent spike in [Ca(2+)](i), albeit lower than in the control group. Such spike was abolished by thapsigargin, and not by removal of extracellular calcium or by K(+), indicating that it was mainly dependent on intracellular calcium stores, as in normal cells. We conclude that bromocriptine treatment partially restores AII response in the hyperplastic pituitary.


Static grey-scale parathyroid ultrasonography: is high-resolution real-time technique required?
Ultrasound has been used with varying success to localise parathyroid adenomas pre-operatively. We have reviewed 61 patients with pre-operative contact-scanning grey-scale parathyroid ultrasonography and subsequent surgical exploration of all four parathyroid glands. Diagnostic accuracy was 91% considering glands examined and 63% considering patients examined. There was one false positive diagnosis. False negative diagnoses (17 adenomas and five ectopic mediastinal tumours) were mainly due to upper pole adenomas, adenomas less than 10 mm X 7 mm in size and ectopic mediastinal adenomas. Static grey-scale ultrasonography is adequate for the pre-operative localisation of parathyroid adenomas, especially when high-resolution technique is not available. In fact, the overall accuracy is comparable to the recently reported diagnostic accuracy rates with high-resolution real-time systems.


A handheld plug-and-play microfluidic liquid handling automation platform for immunoassays.
Lab-on-a-chip technologies and microfluidics have pushed miniaturized liquid handling to unprecedented precision, integration, and automation, which improved the reaction efficiency of immunoassays. However, most microfluidic immunoassay systems still require bulky infrastructures, such as external pressure sources, pneumatic systems, and complex manual tubing and interface connections. Such requirements prevent plug-and-play operation at the point-of-care (POC) settings. Here we present a fully automated handheld general microfluidic liquid handling automation platform with a plug-and-play 'clamshell-style' cartridge socket, a miniature electro-pneumatic controller, and injection-moldable plastic cartridges. The system achieved multi-reagent switching, metering, and timing control on the valveless cartridge using electro-pneumatic pressure control. As a demonstration, a SARS-CoV-2 spike antibody sandwich fluorescent immunoassay (FIA) liquid handling was performed on an acrylic cartridge without human intervention after sample introduction. A fluorescence microscope was used to analyze the result. The assay showed a limit of detection at 31.1 ng/mL, comparable to some previously reported enzyme-linked immunosorbent assays (ELISA). In addition to automated liquid handling on the cartridge, the system can operate as a 6-port pressure source for external microfluidic chips. A rechargeable battery with a 12 V 3000 mAh capacity can power the system for 42 h. The footprint of the system is 16.5 × 10.5 × 7 cm, and the weight is 801 g, including the battery. The system can find many other POC and research applications requiring complex liquid manipulation, such as molecular diagnostics, cell analysis, and on-demand biomanufacturing.


Olfactory signaling via trace amine-associated receptors.
Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors that function as odorant receptors in the main olfactory system of vertebrates. TAARs are monoallelically expressed in primary sensory neurons where they couple to the same transduction cascade as canonical olfactory receptors and are mapped onto glomeruli within a specific region of the olfactory bulb. TAARs have a high affinity for volatile amines, a class of chemicals that are generated during the decomposition of proteins and are ubiquitous physiological metabolites that are found in body fluids. Thus, amines are proposed to play an important role in intra- and interspecific communication such as signaling the sex of the conspecific, the quality of the food source, or even the proximity of a predator. TAARs have a crucial role in the perception of these behaviorally relevant compounds as the genetic deletion of all or even individual olfactory TAARs can alter the behavioral response and reduce the sensitivity to amines. The small size of this receptor family combined with the ethological relevance of their ligands makes the TAARs an attractive model system for probing olfactory perception. This review will summarize the current knowledge on the olfactory TAARs and discuss whether they represent a unique subsystem within the main olfactory system.


Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation.
Administration of azithromycin after allogeneic hematopoietic stem cell transplantation for hematologic malignancies has been associated with relapse in a randomized phase 3 controlled clinical trial. Studying 240 samples from patients randomized in this trial is a unique opportunity to better understand the mechanisms underlying relapse, the first cause of mortality after transplantation. We used multi-omics on patients' samples to decipher immune alterations associated with azithromycin intake and post-transplantation relapsed malignancies. Azithromycin was associated with a network of altered energy metabolism pathways and immune subsets, including T cells biased toward immunomodulatory and exhausted profiles. In vitro, azithromycin exposure inhibited T-cell cytotoxicity against tumor cells and impaired T-cell metabolism through glycolysis inhibition, down-regulation of mitochondrial genes, and up-regulation of immunomodulatory genes, notably SOCS1. These results highlight that azithromycin directly affects immune cells that favor relapse, which raises caution about long-term use of azithromycin treatment in patients at high risk of malignancies. The ALLOZITHRO trial was registered at www.clinicaltrials.gov as #NCT01959100.


Safety assessment of the microalgae Nannochloropsis oculata.
Nannochloropsis oculata is a marine-water microalgae that is considered to be a good source of omega-3 fatty acids, specifically eicosapentaenoic acid (EPA), utilized in the production of an omega-3 oil for use as a dietary supplement. This study investigates the safety of N. oculata in male and female Sprague-Dawley rats administered a 0 or 10 mL/kg bw/rat N. oculata (10E8 viable cells/mL) suspension by oral gavage once daily for 14 consecutive days. No mortalities occurred and no signs of toxicity were observed during the study. No treatment-related effects were seen for body weight, food consumption, urinalysis, clinical chemistry, hematology, gross pathology, organ weights, or histopathology. Although statistically significant effects were noted for some endpoints, none were considered to be of toxicological significance. The N. oculata suspension was concluded to have no toxicity in rats, confirming that the algal strain used in the production of omega-3 oil is not pathogenic when administered orally to rats.


Buffer effects and threshold effects: an alternative interpretation of nonlinearities in the relationship between social support, stress, and depression.
The common interpretation of statistical interactions of global measures of social support and stress in their effects on depression (the "buffer effect" of social support) as reflecting interactive processes within individuals was examined. It was argued that its adequacy depends on incorrect assumptions about the distribution of depressive symptoms within individuals over time and/or different levels of psychosocial adversity. With hypothetical data sets generated under the assumption of a threshold effect in the development of depression and of additive, rather than interactive, effects of social support and stress, it was demonstrated that spurious "buffer effects" of social support can appear in analyses of cross-sectional data. Methodological and substantive implications are discussed, and strategies for study design and data analysis are proposed that allow to assess whether empirical deviations from linearity are more adequately interpreted as a buffer or as a threshold effect.


Induction of pre-early nuclear antigen(s) in HEL cells infected with human cytomegalovirus.
Human cytomegalovirus (HCMV)-specific nuclear antigen could be detected within 1 hr after infection in human embryo lung cells by the anticomplement immunofluorescence (ACIF) test. This antigen has been named the pre-early nuclear antigen (PENA) in this paper. Serum absorption tests suggested that PENA is immunologically different from the early antigen and the major nuclear inclusion antigens detected by the indirect immunofluorescence test before and after viral DNA replication, respectively. PENA-forming ability of the virus corresponded to its plaque forming ability. PENA formation was not affected by phosphonoacetate but was inhibited by the addition of inhibitors of RNA and protein syntheses or by UV-irradiation of infecting virus, suggesting that the formation of PENA depends on the expression of infecting virus gene functions. Virus-specific proteins were isolated by indirect immunoprecipitation from HCMV-infected cells exposed to 35S-methionine. SDS-polyacrylamide gel electrophoresis of the immunoprecipitate showed that at least two species of virus-specific polypeptides with molecular weights o.f 70,000 and 30,000 were synthesized de novo within 3 hr after infection.


Brain-only metastatic breast cancer is a distinct clinical entity characterised by favourable median overall survival time and a high rate of long-term survivors.
The clinical course of breast cancer patients with brain metastases (BM) as only metastatic site (brain-only metastatic breast cancer (BO-MBC)) has been insufficiently explored. All breast cancer patients with BM treated at our institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed. In total, 222 female patients (26% luminal; 47% Her2; 27% triple negative) with BM of MBC were included in this study. In all, 38/222 (17%) BM patients did not develop extracranial metastases (ECM) during their disease course and were classified as BO-MBC. Brain-only-MBC was not associated with breast cancer subtype or number of BM. The median overall survival of BO-MBC patients was 11 months (range 0-69) and was significantly longer than in patients with BM and ECM (6 months, range 0-104; P=0.007). In all, 7/38 (18%) BO-MBC patients had long-term survival of >3 years after diagnosis of BM and long-term survival was significantly more common in BO-MBC patients as compared with BM patients with ECM (P<0.001). Brain-only metastatic behaviour occurs in around 17% of breast cancer with BM and is not associated with breast cancer subtype. Exploitation of all multimodal treatment options is warranted in BO-MBC patients, as these patients have favourable prognosis and long-term survival is not uncommon.


Gout Flares and Mortality After Sodium-Glucose Cotransporter-2 Inhibitor Treatment for Gout and Type 2 Diabetes.
Recurrent flares are the hallmark of clinical manifestation of gout. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a lower risk of incident gout; however, their association with recurrent flares is unknown. To examine the association of SGLT2i vs active comparators (ie, glucagonlike peptide-1 receptor agonists [GLP-1 RA] or dipeptidyl peptidase-4 inhibitors [DPP-4i]) with the risk of recurrent gout flares and all-cause mortality among patients with gout and type 2 diabetes. This population-based retrospective cohort study was performed from January 1, 2013, to March 31, 2022, using a UK primary care database. Participants included patients with gout and type 2 diabetes with visits to their general practitioners. Initiation of treatment with SGLT2i or active comparators. The primary outcome was the number of recurrent gout flares ascertained using recorded codes and prescription records. Secondary outcomes were the first recurrent gout flare and all-cause mortality. The association of SGLT2i compared with active comparators for the risk of recurrent flares, the first recurrent flare, and all-cause mortality was assessed using Poisson regression or the Cox proportional hazards model with propensity score overlap weighting. Of a total of 5931 patients included in the analysis (mean [SD] age, 66.0 [11.6] years; 4604 [77.6%] men), 1548 initiated SGLT2i treatment and 4383 initiated treatment with active comparators during the study period. The relative rate of the recurrent flares with SGLT2i vs active comparators was 0.79 (95% CI, 0.65-0.97). Similar results were observed in the association of SGLT2i with the rate of recurrent flares when compared with DPP-4i or GLP-1 RA. For the first recurrent flare for SGLT2i vs active comparators, rate difference was -8.8 (95% CI, -17.2 to -0.4) per 1000 person-years and the hazard ratio was 0.81 (95% CI, 0.65-0.98). All-cause mortality per 1000 person-years was 18.8 for SGLT2i and 24.9 for active comparators, with rate difference of -6.1 (95% CI, -10.6 to -1.6) per 1000 person-years and hazard ratio of 0.71 (95% CI, 0.52-0.97). The findings of this cohort study suggest that SGLT2i were associated with a lower risk of recurrent gout flares and mortality than their active comparators in patients with gout and type 2 diabetes. These findings further suggest that SGLT2i could help reduce the burden of recurrent gout flares and could also narrow the mortality gap between patients with gout and the general population.


Angiotensin II regulates choroid plexus blood flow by interacting with the sympathetic nervous system and nitric oxide.
Blood flow to the rat choroid plexus has minimal variability when plasma angiotensin II (AII) concentration is changed within a broad range of levels. We tested the hypothesis that a complex interplay of the vasoconstrictor and vasodilator AII actions in choroidal tissue results in small net changes in choroidal blood flow. Blood flow was measured with 123I- or 125I-N-isopropyl-p-iodoamphetamine. AII was infused intravenously (i.v.) at 30 (moderate dose) and 300 ng kg-1 min-1 (high dose), which respectively decreased (15%) and did not change choroidal blood flow. To determine whether AII regulates choroidal blood flow by interacting with the sympathetic nervous system, rats were given phentolamine (1 mg kg-1, i.v.). This alpha-adrenoceptor antagonist by itself did not alter blood flow; however, it attenuated the blood flow-lowering effect of moderate AII dose. Phentolamine also unmasked the vasodilator AII actions at high peptide concentration. beta-Adrenoceptor blockade, with propranolol (1 mg kg-1, i.v.), reduced blood flow (18-20%) and increased vascular resistance (23-26%). During beta-adrenoceptor blockade, a further decrease in blood flow (15-21%) and increase in vascular resistance (23%) was noted when high AII dose was administered. The direct vasoconstrictor effect of AII at moderate dose on choroidal vasculature was examined in rats subjected to chronic bilateral superior cervical ganglionectomy. In these animals, AII decreased blood flow (24%) and increased vascular resistance (24%). To find out whether the hemodynamic AII actions in choroidal tissue are mediated by nitric oxide (NO), Nomega-nitro-l-arginine methyl ester (l-NAME) was used. l-NAME (0.1 mg kg-1, i.v.) by itself did not alter blood flow; however, in l-NAME-treated rats high AII dose lowered blood flow (25-32%) and increased vascular resistance (30-43%). We conclude that the vasoconstrictor AII actions involve a direct peptide effect on the choroidal vascular bed, and the AII-mediated potentiation of sympathetic activity, which results in the activation of alpha-adrenoceptors. The AII-mediated stimulation of sympathetic nerves also results in the beta-adrenoceptor-dependent relaxation of choroidal blood vessels. In addition, choroidal vasodilatory actions of AII are NO-mediated.


Patient-Derived Bladder Cancer Organoid Models in Tumor Biology and Drug Testing: A Systematic Review.
Bladder cancer is a common and highly heterogeneous malignancy with a relatively poor outcome. Patient-derived tumor organoid cultures have emerged as a preclinical model with improved biomimicity. However, the impact of the different methods being used in the composition and dynamics of the models remains unknown. This study aims to systematically review the literature regarding patient-derived organoid models for normal and cancer tissue of the bladder, and their current and potential future applications for tumor biology studies and drug testing. A PRISMA-compliant systematic review of the PubMED, Embase, Web of Sciences, and Scopus databases was performed. The results were analyzed based on the methodologies, comparison with primary tumors, functional analysis, and chemotherapy and immunotherapy testing. The literature search identified 536 articles, 24 of which met the inclusion criteria. Bladder cancer organoid models have been increasingly used for tumor biology studies and drug screening. Despite the heterogeneity between methods, organoids and primary tissues showed high genetic and phenotypic concordance. Organoid sensitivity to chemotherapy matched the response in patient-derived xenograft (PDX) models and predicted response based on clinical and mutation data. Advances in bioengineering technology, such as microfluidic devices, bioprinters, and imaging, are likely to further standardize and expand the use of organoids.


"Lymphocyte population in peripheral blood in children and adolescents with graves disease. Potential predictive tool for severity of the disease".
To date, few data are available on the prognostic role of lymphocyte subsets in pediatric Graves' Disease (GD). The aim of this retrospective study is to analyze the role of lymphocyte subtypes in predicting the severity of GD. Data of 10 pediatric subjects aged <18 years with GD onset in the period November 2017-April 2021 were collected. The lymphocyte population was assessed at the onset of GD as well as hormonal and clinical data. The follow-up period was 2.4 ± 0.8 years. Pearson correlation coefficient between CD4+ /CD8+ ratio and fT3 levels and thyroid volume at diagnosis was 0.72 (p = 0.04) and 0.81 (p = 0.004) respectively; that between CD4+ /CD8+ ratio and the TRAb titer at diagnosis and after 6, 12 and 24 months was 0.89, 0.89, 0.73 and 0.77 respectively (p = 0.02, p = 0.01, p = 0.03 and 0.04). The correlation coefficient of anti-thyroid drug (ATD) dose after 6 and 12 months with CD4+ /CD8 ratio was 0.88 and 0.78 (p = 0.001 and p = 0.02 respectively). Patients with a higher CD4+ /CD8+ ratio at diagnosis displayed higher fT3 levels (28.73 ± 2.18 vs 13.48 ± 2.19 pmol/L, p = 0.03) and higher TRAb titers (28.9 ± 11.2 vs 4.88 ± 0.97, p = 0.01). CD4+/CD8+ ratio appears as a promising predictive tool to be considered together with other prognostic factors to better manage pediatric GD. These preliminary data need to be confirmed over a longer follow-up period and in larger cohorts.


The inhibitory effect of paraquat on histamine and isoproterenol induced changes of cyclic nucleotides in rat lung slices.
The incubation of rat lung slices with paraquat ion (10(-4) M) had no effect on cAMP and cGMP levels of the rat lung slices. The preincubation with the same concentration of paraquat inhibited the cAMP elevating effect of histamine (10(-5) M) and isoproterenol (10(-5) M) and reduced the cGMP level to approximately 50% of the level obtained without preincubation with paraquat.


Effects of fire on soil organic carbon, soil total nitrogen, and soil properties under rotational shifting cultivation in northern Thailand.
Fire has been used for land clearing under rotational shifting cultivation (RSC) in Northern Thailand for a long time. However, the effects of fire on soil organic carbon (SOC), soil total nitrogen (STN), and soil properties are not well understood. We determined SOC, STN, and soil properties of the topsoil layer (0-30 cm) along a fallow chronosequence under RSC and assessed how fire affects SOC, STN, and soil properties. Eight fields at Ban Mae Pok, Mae Chaem District, Chiang Mai Province, Northern Thailand, were investigated. The levels of SOC, STN, and soil properties were observed at three time points: pre-burning, post-burning (5 minutes after burning), and post-harvest (nine months after burning). The highest SOC and STN stocks, organic matter (OM), and clay content were observed for the longest fallow period (7 years fallow), whereas the shortest period (1 year fallow) resulted in the lowest SOC and STN stocks. Fire caused no significant changes in SOC, STN, and some soil properties (soil texture, available P, exchangeable K, exchangeable Ca, exchangeable Mg, bulk density, and OM) because of the low fire intensity and short fire duration. Only pH and electrical conductivity were significantly increased (p ≤ 0.05) after burning due to the demobilization of base cations in burnt vegetation and incorporation into the soil with ashes and wood charcoal. Although fire may still be necessary for RSC, maintaining the fire intensity below 380 °C to reduce SOC losses and appropriate post-fire management strategies to reduce STN losses are crucial.


Methods of PARP-1 Determination and its Importance in Living Organisms.
PARP-1 is one of the 18 PARP enzymes that are involved in important processes at the cellular level. The most important tasks of PARP-1 are to detect and repair DNA damage and to prevent processes of apoptosis. By finding and using new strategies for marking and detecting the activity of this protein, it is possible to identify more and more tasks in which it participates. In pathological states, PARP-1 activity increases significantly. Since the 1980s, scientists have been searching for and discussing substances that may inhibit PARP-1 activity and disrupt DNA damage response pathways. In this way, unwanted cells could be destroyed. The paper presents a short description of the methods used in the determination of PARP-1 by various research groups. A critical approach to each of them was also made by pointing to the advantages and disadvantages of the described analytical methods. The literature review contains information on methods useful for PARP-1 determination, such as SPR, QCM, CL and FL, DPV, SDS-PAGE with MS, MALDI MS, Western Blot, ELISA and ATR-FTIR spectroscopy. It also includes analysis of the results of research on inhibitors that may be effective in the diagnosis and treatment of cancer and other diseases.


The Development of High-Density Vertical Silicon Nanowires and Their Application in a Heterojunction Diode.
Vertically aligned p-type silicon nanowire (SiNW) arrays were fabricated through metal-assisted chemical etching (MACE) of Si wafers. An indium tin oxide/indium zinc oxide/silicon nanowire (ITO/IZO/SiNW) heterojunction diode was formed by depositing ITO and IZO thin films on the vertically aligned SiNW arrays. The structural and electrical properties of the resulting ITO/IZO/SiNW heterojunction diode were characterized by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and current-voltage (I-V) measurements. Nonlinear and rectifying I-V properties confirmed that a heterojunction diode was successfully formed in the ITO/IZO/SiNW structure. The diode had a well-defined rectifying behavior, with a rectification ratio of 550.7 at 3 V and a turn-on voltage of 2.53 V under dark conditions.


[Laparoscopic transhiatal esophagectomy: outcomes].
The laparoscopic transhiatal esophagectomy for benign or malignant disease is a complex operation associated with a high rate of morbidity and mortality. In the last decade this procedure gained popularity and acceptance for treatment of the esophagus cancer and other benign diseases. To perform a retrospective analysis in patients with esophageal cancer that was underwent a laparoscopic transhiatal esophagectomy, demonstrated pre and post operative complications and immediate result. From November 1993 to June 2005, 72 patients underwent laparoscopic transhiatal esophagectomy. Sixty-four with malignant neoplasm of esophagus. The males are predominant, and the mean age was 56.5 years. The abdominal part of the operation was totally laparoscopic and the cervical one was made the conventional way. The stomach was pulled up to the neck by the posterior mediastinum. The laparoscopic transhiatal esophagectomy was initiated in 64 patients. Four patients were converted to open surgery. The mean operation time was 153 minutes. The incidence of cervical fistula was 14.06%. The mortality rate 5.6%. Laparoscopic transhiatal esophagectomy is a secure option in experience centers. The morbility is low, with a faster return to normal activity. Maybe in fact this procedure may be reminded and ponder in the treatment of esophageal disease.


Visualizing Chromosome Territories and Nuclear Architecture of Large Plant Genomes Using Alien Introgressions.
Visualization of chromosome territories is a challenging task in plant genomes due to the lack of chromosome-specific probes, especially in species with large genomes. On the other hand, combination of flow sorting, genomic in situ hybridization (GISH), confocal microscopy, and employment of software for 3D modeling enables to visualize and characterize chromosome territories (CT) in interspecific hybrids. Here, we describe the protocol for the analysis of CTs in wheat-rye and wheat-barley hybrids, including amphiploids and introgression forms, where a pair of chromosomes or chromosome arms from one species is introgressed into the genome of another species. In this way, the architecture and dynamics of CTs in various tissues and different stages of cell cycle can be analyzed.


Role of modifiable risk factors in life expectancy in the elderly.
The aim of the present study was to evaluate the role of 'modifiable' risk factors, assessed between the ages of 60 and 70 years, in late survival. The study population included subjects aged 60-70 years, who had a standard health examination at the IPC Center, and who could potentially reach the age of 80 years for men and 85 years for women at the end of the follow-up period. The role of 'modifiable' risk factors was assessed by comparing subjects who died before the age of 80 years for men (n=1333) and before 85 years for women (n=543) to subjects who survived beyond these ages (3681 men, 1910 women). Multivariate analyses were conducted to determine which parameters were independently associated with survival to an advanced age. The multivariate analysis showed a decreased probability of late survival with higher pulse pressure (P<0.0001), higher heart rate (P<0.002), higher glycemia (P<0.0034), and an increased probability with regular physical activity (P<0.0001). A significant interaction between heart rate and gender (P<0.01) was observed, indicating that heart rate was a predictor of late survival in men but not in women. Body mass index, cholesterol and triglyceride levels, and diastolic blood pressure and tobacco smoking were not associated with late survival in this population. A systematic search for certain risk factors in an elderly patient can have a significant impact on late survival and can lead to the establishment of priority goals, such as increasing physical activity and reducing blood pressure, heart rate and glycemia.


ECG gated thallium 201 myocardial images: value in detecting multivessel disease in patients on anti anginal therapy 1-3 months after myocardial infarction.
ECG gated 201Tl scintigraphy was compared to non gated images for detecting 2-3 vessel disease 1-3 months after a first uncomplicated myocardial infarction. In all, 111 patients on anti anginal treatment underwent coronary arteriography and stress thallium imaging; 39 showed single vessel disease (SVD), and 72 multivessel disease (MVD). Sensitivity of black and white analog images was 82% for SVD and 8% for MVD. Sensitivity of computerized colored static images was 87% for SVD and 33% for MVD. For gated images, sensitivity was 100% and 92% in patients with SVD and MVD respectively. Specificity for detecting MVD was 95% for black and white images, 77% for computerized colored static images, and 69% for ECG gated images. Thus, ECG gated exercise 201TL scintigraphy is useful for predicting the extent of coronary artery disease 1-3 months after myocardial infarction in patients on anti anginal therapy.


In situ solvent formation microextraction in the presence of ionic liquid for preconcentration and speciation of arsenic in saline samples and total arsenic in biological samples by electrothermal atomic absorption spectrometry.
In this modality, the extraction phase is formed in situ while simultaneously extracting analytes. First, a water-miscible ionic liquid (IL) ([Hmim][BF(4)]), capable of complete dissolving in the aqueous solution, was added to the sample. Then, an ion-exchange reagent (NaPF(6)) was added to obtain the hydrophobic IL ([Hmim][PF(6)]) that acted as the analyte extractant to form the cloudy homogeneous solution for the preconcentration and speciation of trace amounts of As (III) and As (V) with electrothermal atomic absorption spectrometry (ETAAS) detection. In situ solvent formation microextraction is a simple and rapid method for extraction and preconcentration of metal ions from sample solutions containing high concentration of salt. Some effective factors that influence the microextraction efficiency were investigated and optimized. Under the optimum experimental conditions, the limit of detection (3 σ) and the enrichment factor were 6 ng L(-1) and 198, respectively. The obtained relative standard deviation was 4.78%. The proposed method was successfully applied for the determination of As (III) and As (V) in water samples, food salts, and total As in biological samples.


Longitudinal versus transverse incision for common femoral artery exposure: a systematic review and meta-analysis.
A longitudinal or a transverse incision is routinely used for common femoral artery (CFA) exposure. Some believe a transverse incision is associated with a lower incidence of postoperative complications. We performed a systematic review and meta-analysis to evaluate the risk of postoperative surgical site infection, lymphatic complications, wound dehiscence and haematoma formation when using a longitudinal or transverse incision for CFA exposure. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were adhered to. We searched various databases such as MEDLINE via PubMed and Embase for relevant studies from inception till 31 May 2020. Relevant search terms such as 'longitudinal', 'transverse', 'vertical', 'horizontal', 'femoral', 'incision' were used. We included both randomized controlled trials and case-controlled studies, and extracted data related to study characteristics and postoperative complications. We assessed risk of bias using the Cochrane risk of bias tool and the Newcastle-Ottawa scale. A random-effects meta-analysis was performed to obtain the pooled proportions and risk ratios (RR) for our study outcomes. We included seven studies with a total of 5922 groin incisions. A longitudinal incision was associated with a significantly higher incidence of wound infection (RR 2.93, 95% confidence interval (CI) 1.12-7.70, P = 0.03) and wound dehiscence (RR 2.87, 95% CI 1.06-7.77, P = 0.04). The risk of lymphatic complications (RR 1.09, 95% CI 0.39-3.05, P = 0.87) and wound haematoma (RR 2.85, 95% CI 0.88-9.21, P = 0.08) were similar. A longitudinal incision may be associated with a higher incidence of wound infection and wound dehiscence, as compared to using a transverse incision for CFA exposure.


Constructive confrontation and other referral processes.
Constructive confrontation is a workplace strategy used to identify alcoholic employees and motivate them to change their behavior, either with their own resources or with the counseling services provided by employee assistance programs. This paper describes the strategy's use by supervisors, peers, unions, and occupational groups, and it reviews the effectiveness of the evaluation research. The paper concludes with a discussion of "self-referral" in employee assistance.


Knowledge and Practices of Child Eye Healthcare Among Parents in Aseer Region, Saudi Arabia.
The majority of causes of childhood blindness are preventable and treatable. There are an estimated 1.4 million blind children worldwide, with roughly three-quarters of them living in developing countries. In most low-income countries, school-age children account for 20%-30% of the total population. To evaluate parents' knowledge, attitudes, and practices related to pediatric eye medical services in Saudi Arabia's Aseer region. A descriptive cross-sectional approach was used targeting all parents in the Aseer region. Data were collected using a structured questionnaire developed by the study investigators. The questionnaire included parents' sociodemographic data and a family history of blindness or visual disability. Parents' awareness regarding pediatric eye care was assessed using relevant items. The parents' practices and attitudes regarding eye care were also assessed within the questionnaire. The study included 899 parents who replied to the online questionnaire in its entirety. Some 54% of the responding parents were aged 30-50 years, and 51.2% were males. Of the parents, 46.2% had a university-level education, and 48.5% accompanied their children for eye examinations. About 65% of the parents knew about clinics for eye examinations, and 63.3% of them knew that blind children could learn. In total, more than one-third of the parents were aware of pediatric eye care. The study found that parents were aware of pediatric eye health and sought eye care for their children. More effort should be put forth through planned awareness programs to educate parents and assist them in overcoming the fears and barriers that keep them from seeking eye care for their children.


Efficacy of 2-(3,4-dimethyl-2,5-dihydro-1h-pyrrole-2-yl)-1-methylethyl pentanoate in a murine model of invasive aspergillosis.
2-(3,4-Dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, an antifungal compound, was found to be nontoxic to RAW cells up to a concentration of 312.5 microg/ml, whereas amphotericin B was lethal to all cells at 37.5 microg/ml. The treatment of Aspergillus fumigatus-infected mice with a dose of 200.0 mg of compound/kg of body weight increased their survival rate by 60%, with a decrease in CFU in organ tissues. The protection afforded by the compound against experimental aspergillosis was found to be dose dependent.


Evolution of operating microscopes and development of 3D visualization systems for intraocular surgery.
The recent development of high-resolution, heads-up, 3D visualization microscopy systems has provided new technical and visualization options for ophthalmic surgeons. In this review, we explore the evolution of microscope technologies, the science behind modern 3D visualization microscopy systems, and the practical benefits (as well as disadvantages) that these systems provide over conventional microscopes for intraocular surgical practice. Overall, modern 3D visualization systems reduce the requirements for artificial illumination and provide enhanced visualization and resolution of ocular structures, improving ergonomics, and facilitating a superior educational experience. Even when considering their disadvantages, such as those related to technical feasibility, 3D visualization systems have an overall positive benefit/risk ratio. It is hoped these systems will be adopted into routine clinical practice, pending further clinical evidence on the benefits they may provide on clinical outcomes.


Immunohistochemical evidence of the presence of estrogen and progesterone receptors in the same neurons of the guinea pig hypothalamus and preoptic area.
Estrogen and progesterone interact in the regulation of various brain functions including mechanisms controlling gonadotropin secretion and female sexual behavior. Various methods have been used to map the regions where these hormones act and where specific receptors can be detected. However, it remains unknown if both steroids act on the same neuron or if there are neural populations responding to either one or the other of these hormones To answer this question, we used various immunocytochemical procedures to detect estrogen and progesterone receptors (ER-IR and PR-IR) on the same histological section, taking advantage of the fact that anti-ER monoclonal antibodies were raised from rats whereas anti-PR monoclonal antibodies were raised from mice. Initial experiments showed that the number of cells displaying ER and PR immunoreactivity changed with hormonal treatment. Prolonged treatment of ovariectomized guinea pigs with high doses of estradiol benzoate (EB) (10 or 15 micrograms/day for 4 or 6 days) increased the number of PR-positive cells in the preoptic area and the hypothalamus. Inversely, with this estrogen priming regimen the number of ER-positive cells decreased, as did the immunostaining intensity in their nuclei. With a lower dose of estrogen administered for a shorter period (2-microgram dose of EB for 2 days) the two receptor populations could be easily observed. Under these hormonal conditions, the sequential procedure revealed that the vast majority of cells containing ER-IR in the preoptic area (nucleus preopticus periventricularis, medialis) and the mediobasal hypothalamus (nucleus periventricularis, arcuatus, ventrolateral part of nucleus ventromedialis and premamillaris) showed PR immunoreactivity. This was true regardless of the order in which dual immunocytochemical staining was performed. There were, however, a few ER-positive/PR-negative cells in these regions. However, only ER-positive neurons were found in the n. interstitialis stria terminalis, the n. amygdaloideus medialis and the n. supraopticus. Thus, in guinea pigs receiving moderate doses of estrogen, all PR-positive cells contain ER-IR whereas there is a population of ER-positive cells which are devoid of PR-IR.


Assessment of the root apex position of impacted maxillary canines on panoramic films.
In this study, we aimed to analyze the root apex positions of impacted maxillary canines on panoramic radiographs according to their labiopalatal positions and to propose a new panoramic radiographic predictor of impacted maxillary canines. Paired panoramic films and cone-beam computed tomography images of 104 patients with unilateral impacted maxillary canines were selected. The sector locations of the impacted canine root apices on the panoramic radiographs were compared with the labiopalatal positions of impacted maxillary canines on cone-beam computed tomography. Statistical correlations between panoramic and cone-beam computed tomography findings were examined with the chi-square test. A statistically significant association was observed between the sector locations of impacted canine root apices and the labiopalatal positions of the canines (P <0.001). The root apices of labially impacted canines were more frequently located in sector 2 (corresponding to the lateral incisor position), those of palatally impacted canines were more frequently located in sector 4 (corresponding to the first premolar), and those of midalveolus impacted canines were more frequently located in sector 3 (corresponding to the canine). On panoramic films, the root apices of palatally impacted canines tended toward the root apices of the maxillary first premolars, whereas those of labially impacted canines tended toward the root apices of the maxillary lateral incisors. Therefore, the sector locations of impacted canine root apices on panoramic radiographs could be used for the early prediction of maxillary canine impactions and determination of the labiopalatal positions of impacted canines.


To select effective interventions for pro-environmental behaviour change, we need to consider determinants of behaviour.
Encouraging pro-environmental behaviour is necessary to reduce CO2 emissions and limit global climate change. Many reviews and meta-analyses have been published examining the effectiveness of interventions to promote pro-environmental behaviour. Yet, it remains unclear which interventions are most effective, when and why. Because interventions are more likely to encourage pro-environmental behaviour when they target key determinants of the relevant behaviour, it is critical to understand which interventions target which determinants. We introduce a classification system that links six types of interventions to 13 determinants of environmental behaviour. Our classification enables a theory-based understanding of when and why interventions are effective (or not) in encouraging pro-environmental behaviour and provides guidelines to practitioners to select interventions that are most likely to change the key determinants of a specific target behaviour, and thus likely to be the most successful in changing behaviour in the given context.


Performance assessment of improved composting system for food waste with varying aeration and use of microbial inoculum.
Wet waste recycling at generation point will alleviate burden on the overflowing waste dumpsites in developing nations. Drum composting is a potential treatment option for such waste at individual or community level. The present study was aimed to produce compost from wet waste (primarily comprising food waste) in composting drums modified for improved natural air circulation. Effect of microbial inoculum and waste turning on composting process was also studied. The final results showed the production of matured and stable compost in the modified drums. Addition of the microbial inoculum resulted in thermophilic phase within a week time. The self-heating test and germination index (>80%) showed the production of non-phytotoxic and mature compost in the modified drums after 60days. The change in microbial population, humic substances and biological parameters (lignin, cellulose and hemicellulose) during the study is discussed. Moreover, the reduction in waste mass and volume is also reported.


IgM ocular cicatricial pemphigoid: a unique insight into the immune system.
A 42-year-old man with ocular erythema and scarring had a conjunctival biopsy revealing depostion of IgM and C3 without IgG at the epithelial basement membrane zone. Treatment with doxycyline, dapsone, and mycophenolate mofetil was unsuccessful and treatment with rituximab has led to partial remission of the conjunctival inflammation. He has undergone 4 cycles of rituximab treatment at intervals of 12 to 18 months.


Management of major hemoptysis in patients with cystic fibrosis.
Although bronchoscopy remains the best definitive method for localization of the site of hemorrhage in patients who have massive hemopytsis, angiography remains an important adjunct to this localization. When combined with embolization of the bleeding bronchial artery, it is an effective method of therapy for the management of massive hemoptysis in patients with cystic fibrosis.


500 Cases of High-intensity Focused Ultrasound (HIFU) Ablated Uterine Fibroids and Adenomyosis.
Clinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented. This is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients' uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10-16 cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months. Three months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort. HIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.


Correlation between beat-to-beat blood pressure variability and arterial stiffness in healthy adults in the cold pressor test.
Blood pressure variability has a great effect on the progression of arterial stiffness, which has increasingly become a hot research topic recently. In this study, beat-to-beat recordings of blood pressure (BP), heart rate, cardiac output, total peripheral resistance, and left ventricular ejection time during the cold pressor test (CPT) were analyzed together. We recruited 101 young Chinese subjects (aged 21-33) with no known history of high BP into the study. We found that the mean level of beat-to-beat BP and the average real variability and successive variation of beat-to-beat diastolic BP variability in the CPT showed significant correlations with pulse wave velocity (PWV) (r = 0.22-0.34, P < 0.05). In addition, we also found correlations between beat-to-beat heart rate and heart rate variability indices and PWV in each phase of the CPT. At the same time, the standard deviation of the R-R intervals and square root of the mean squared difference of successive R-R intervals in the cold stimulus phase also showed significant correlations with PWV (r = 0.23-0.24, P < 0.05). In conclusion, the level and variability of beat-to-beat BP have a strong influence on arterial stiffness.


Effect of creep feeding on structural and functional changes of the gut of early weaned pigs.
Dose-dependent hypersensitivity responses mounted against antigenic constituents of creep feeds have been previously implicated in intestinal damage, digestive disorders and impaired performance of early weaned pigs. In the present study biochemical and histological investigations of the small intestine were undertaken to determine the putative relationship between creep feed level and hypersensitivity response in pigs weaned at 14 days. Creep feed was administered by gastric intubation and weaned pigs received the same diet by gastric intubation for five days. Mucosal structure and function at weaning were not affected by creep feeding regimen. Villus height decreased and crypt depth increased in weaned compared to suckled pigs, but morphology was unaffected by prior exposure to creep. Xylose absorption was not influenced by either creep feed level or weaning. Intraepithelial lymphocyte numbers increased during weaning but were not affected by the creep feeding regimen. Mucosal carbohydrase activity in weaned pigs was not significantly affected by preweaning treatment. The results do not support the hypothesis that post weaning changes in structure and function of the gut are related to creep feed level or to immune responses to dietary antigens.


Clinical operations of academic versus non-academic emergency departments: a descriptive comparison of two large emergency department operations surveys.
Academic and non-academic emergency departments (EDs) are regularly compared in clinical operations benchmarking despite suggestion that the two groups may differ in their clinical operations characteristics. and outcomes. We sought to describe and compare clinical operations characteristics of academic versus non-academic EDs. We performed a descriptive, comparative analysis of academic and non-academic adult and general EDs with 40,000+ annual encounters, using the Academy of Academic Administrators of Emergency Medicine (AAAEM)/Association of Academic Chairs of Emergency Medicine (AACEM) and Emergency Department Benchmarking Alliance (EDBA) survey results. We defined academic EDs as primary teaching sites for emergency medicine (EM) residencies and non-academic EDs as sites with minimal resident involvement. We constructed the academic and non-academic cohorts from the AAAEM/AACEM and EDBA surveys, respectively, and analyzed metrics common to both surveys. Eighty and 454 EDs met inclusion criteria for academic and non-academic EDs, respectively. Academic EDs had more median annual patient encounters (73,001 vs 54,393), lower median proportion of pediatric patients (6.3% vs 14.5%), higher median proportion of EMS patients (27% vs 19%), and were more commonly designated as Level I or II Trauma Centers (94% vs 24%). Median patient arrival-to-provider times did not differ (26 vs 25 min). Median length-of-stay was longer (277 vs 190 min) for academic EDs, and left-before-treatment-complete was higher (5.7% vs 2.9%). MRI utilization was higher for academic EDs (2.2% patients with at least one MRI vs 1.0 MRIs performed per 100 patients). Patients-per-hour of provider coverage was lower for academic EDs with and without consideration for advanced practice providers and residents. Demographic and operational performance measures differ between academic and non-academic EDs, suggesting that the two groups may be inappropriate operational performance comparators. Causes for the differences remain unclear but the differences appear not to be attributed solely to the academic mission.


Contact Dermatitis for the Practicing Allergist.
This article provides an overview of important practice recommendations from the recently updated Contact Dermatitis Practice Parameter. This updated parameter provides essential recommendations pertaining to clinical history, physical examination, and patch testing evaluation of patients suspected of allergic contact dermatitis. In addition to providing guidance for performing and interpreting closed patch testing, the updated parameter provides concrete recommendations for assessing metal hypersensitivity in patients receiving prosthetic devices, for evaluating workers with occupational contact dermatitis, and also for addressing allergic contact dermatitis in children. Finally, the document provides practical recommendations useful for educating patients regarding avoidance of exposure to known contact sensitizers in the home and at work. The Contact Dermatitis Parameter is designed as a practical, evidence-based clinical tool to be used by allergists and dermatologists who routinely are called upon to evaluate patients with skin disorders.


Exploring Mental Health and Development in Refugee Children Through Systematic Play Assessment.
To evaluate a standardized play observation as a measure of young children's mental health and development in a clinical and refugee population. We conducted individual play observations with 70 refugee children aged 3- to 6-years and compared them to a clinical group of 111 age-matched children regarding their level of play development, social interaction during play, traumatic re-enactments, and emotionless-cold play. Additionally, we assessed children's mental health, social-emotional development and markers of adversity by parent and educator report as well as their IQ-test scores and learning performance and related these factors to the play variables. Play variables were significantly correlated with IQ-test scores (r = 0.184, p = 0.037), learning performance (r = 0.208, p = 0.010) and vocabulary (r = 0.208, p = 0.021) in the comparison group and with social-emotional development in educator report (r = 0.368, p = 0.011), time spent in Germany (r = 0.342, p < 0.001) and parental distress (r = - 0.292, p = 0.034) in the refugee group. Children with more parent-reported adverse experiences showed less social-interactive play in the overall sample (r = - 0.178, p = 0.011). Our child-centered approach to standardized play observation augments information obtained from parent and educator reports and can provide valuable insights in subgroups where other commonly used tests are not available or applicable.


Correction: KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Direct peroral cholangioscopy with a conventional videogastroscope in a transplanted patient with anastomotic stricture and choledocholithiasis.
Biliary strictures are one of the most common adverse events after liver transplantation, occurring in as many as 40% of patients in the postoperative period. The optimal strategy for treating these strictures remains to be defined. Direct POC is a useful technique for the study and treatment of biliary diseases, providing high quality endoscopic imaging of the biliary tree and anastomotic strictures.


Oxoglutarate dehydrogenase and acetyl-CoA acyltransferase 2 selectively associate with H2A.Z-occupied promoters and are required for histone modifications.
Histone H2A.Z plays an essential role in regulating transcriptional rates and memory. Interestingly, H2A.Z-bound nucleosomes are located in both transcriptionally active and inactive promotors, with no clear understanding of the mechanisms via which it differentially regulates transcription. We hypothesized that its functions are mediated through recruitment of regulatory proteins to promoters. Using rapid chromatin immunoprecipitation-mass spectrometry, we uncovered the association of H2A.Z-bound chromatin with the metabolic enzymes, oxoglutarate dehydrogenase (OGDH) and acetyl-CoA acyltransferase 2 (ACAA2). Recombinant green florescence fusion proteins, combined with mutations of predicted nuclear localization signals, confirmed their nuclear localization and chromatin binding. Conclusively, chromatin immunoprecipitation-deep sequencing, confirmed the predominant association of OGDH and ACAA2 with H2A.Z-occupied transcription start sites and enhancers, the former of which we confirmed is conserved in both mouse and human tissue. Furthermore, H2A.Z-deficient human HAP1 cells exhibited reduced chromatin-bound metabolic enzymes, accompanied with reduced posttranslational histone modifications, including acetylation and succinylation. Specifically, knockdown of OGDH diminished H4 succinylation. Thus, the data reveal that select metabolic enzymes are assembled at active, H2A.Z-occupied, promoters, for potential site-directed production of metabolic intermediates that are required for histone modifications.


Caring in an Algorithmic World: Ethical Perspectives for Designers and Developers in Building AI Algorithms to Fight Fake News.
This article suggests several design principles intended to assist in the development of ethical algorithms exemplified by the task of fighting fake news. Although numerous algorithmic solutions have been proposed, fake news still remains a wicked socio-technical problem that begs not only engineering but also ethical considerations. We suggest employing insights from ethics of care while maintaining its speculative stance to ask how algorithms and design processes would be different if they generated care and fight fake news. After reviewing the major characteristics of ethics of care and the phases of care, we offer four algorithmic design principles. The first principle highlights the need to develop a strategy to deal with fake news on the part of the software designers. The second principle calls for the involvement of various stakeholders in the design processes in order to increase the chances of successfully fighting fake news. The third principle suggests allowing end-users to report on fake news. Finally, the last principle proposes keeping the end-user updated on the treatment in the suspected news items. Implementing these principles as care practices can render the developmental process more ethically oriented as well as improve the ability to fight fake news.


Defatted algal biomass as feedstock for short chain carboxylic acids and biohydrogen production in the biorefinery format.
The objective of the study was to evaluate the potential application of defatted algal biomass (DAB) residue as a resource for biobased product synthesis in the biorefinery framework. Acid-catalyzed pretreatment of DAB residue resulted in higher reducing sugars (RS) solubilization (0.26 g RS/g DAB) than corresponding base method (0.19 g RS/g DAB). Subsequently, resulting RS were acidogenically fermented for the production of Bio-H2 and short chain carboxylic acids (SCA)/volatile fatty acids (VFA) at varying redox conditions (pH: 6, 7 and 10). Biosystem with pH-6 resulted in higher SCA (0.54 g SCA/g RS) and Bio-H2 production (0.83 l) followed by pH-10 (0.43 g SCA/g RS, 0.71 l) and pH-7 (0.27 g SCA/g RS, 0.48 l). Higher SCA production in pH-6 system resulted in maximum acidification (23%). Algal biomass majorly derived from CO2 and its residues after lipids extraction accounted as major feedstock for acidogenic product synthesis. Evaluation of these studies using DAB residues offers sustainability to algal refineries on its entirety use.


Changes in the physicochemical components, polyphenol profile, and flavor of persimmon wine during spontaneous and inoculated fermentation.
Changes in the oenological parameters, total phenols, total flavonoids, and individual phenols of persimmon during spontaneous and inoculated fermentation were investigated. The volatile compounds and sensory character of the persimmon wine were compared and evaluated simultaneously. Results show that at the end of fermentation, spontaneous persimmon wine (SPW) has higher contents of total flavonoids, total phenols yet lower concentrations of alcohol and volatile compounds than inoculated persimmon wine (IPW). Catechin, salicylic acid, quercetin, and vanillic acid were the main phenolic compounds in both types of persimmon wine. There are six volatile components in the IPW with an OAV greater than 1, which are isoamyl acetate, ethyl hexanoate, methyl octanoate, ethyl octanoate, phenethyl acetate, and 2, 4-di-tert-butylphenol, and these compounds contribute to the IPW with brandy and fruity sensory properties, while only three volatile components in SPW have OAV greater than 1, which are isoamyl acetate, ethyl hexanoate, and ethyl octanoate. Spontaneous fermentation increased the proportion of esters and alcohols in the overall volatile compounds. During sensory evaluation, IPW was characterized by "brandy," "bitterness," and low "sweetness," and SPW has a high score of "sweetness," "balance," desirable "color," and "body."


A problem in rotation therapy with X-rays: dose distributions with an axis of symmetry.
We give the equations which need to be solved to extend the work of Brahme, Roos, and Lax to dose distributions which are not circularly symmetrical. These equations do not contain the linear absorption coefficient, mu, explicitly so they are valid in principle for any mu. The general solution of these equations has not been found, but the solution given by Brahme, Roos, and Lax is used to extend their work to simple dose distributions with an axis of symmetry. Some examples are given and discussed.


Clinical factors to predict the outcome of external cephalic version: a metaanalysis.
The objective of the study was to systematically review the medical literature reporting on potential clinical prognosticators for the outcome of external cephalic version (ECV). Medline, EMBASE, and Cochrane Central Register of Controlled Trials were searched. Studies reporting on potential clinical prognosticators and ECV success rates that allowed construction of a 2 x 2 table were selected. We detected 53 primary articles reporting on 10,149 women. Multiparity (P >/= 1.00; odds ratio [OR], 2.5; 95% confidence interval [CI], 2.3-2.8), nonengagement of the breech (OR, 9.4; 95% CI, 6.3-14), a relaxed uterus (OR, 18; 95% CI, 12-29), a palpable fetal head (OR, 6.3; 95% CI, 4.3-9.2), and maternal weight less than 65 kg (OR, 1.8; 95% CI, 1.2-2.6) were predictors for successful external cephalic version. Success of an ECV attempt is associated with clinical factors. This should be taken into account in the counseling of women prior to an ECV attempt.


Phenylephrine-induced neurogenic prostatitis facilitates the promotion of PIN-like lesions in rats.
Atypical prostate hyperplasia, resembling PIN lesions in men, together with chronic inflammatory exudates, have been reported after chronic administration of phenylephrine (PE). The present study aims to characterize the evolution of the expression of typical leukocyte markers immunohistochemically as correlated to the promotion of PIN lesions. Adolescent rats received injections of PE (subcutaneously) (10 mg/kg BW/per day) and were euthanized 3, 8 hr, 1, 3, 7, 14 days thereafter. The dissected prostates were fixed in formalin, and paraffin embedded sections were cut and immunoreacted. PE exerted a time related bi-phasic effect on the rat prostate. A first inflammatory reaction phase took place at 3-8 hr post injection characterized by vascular dilatation, congestion, edema, and massive leukocytic infiltrate, mainly of ED1+ cells. At 24 hr, the amount of ED1+ cells decreased approaching the equivalent values of ED2+, CD8+ cells, and mastocytes. Their values remained relatively high for the rest of the experimental period. A second phase of proliferative changes, consisting of healing fibrosis as well as dysplastic epithelial lesions, similar to human PIN lesions, appeared on the 7th day. Neuro-immune interactions promote prostatic fibrosis and dysplastic changes; these being preceded by an acute and transient inflammatory reaction.


Elemental analysis of Egyptian phosphate fertilizer components.
The accumulation of certain elements in vitally important media such as water, soil, and food is undesirable from the medical point of view. It is clear that the fertilizers vary widely in their heavy metals and uranium content. A shielded high purity germanium HPGe detector has been used to measure the natural concentration of 238U, 232Th, and 40K activities in the phosphate fertilizer and its components collected from Abu-Zaabal fertilizers and chemical industries in Egypt. The concentration ranges were 134.97-681.11 Bq kg(-1), 125.23-239.26 Bq kg(-1), and 446.11-882.45 Bq kg(-1) for 238U, 232Th, and 40K, respectively. The absorbed dose rate and external hazard index were found to be from 177.14 to 445.90 nGy h(-1) and 1.03 to 2.71 nGy y(-1), respectively. The concentrations of 22 elements (Be, Na, Mg, Si, P, S, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Zr, Mo, Cd, Ba) in the samples under investigation were determined by inductively coupled plasma optical-emission spectrometry (ICP-OES). The results for the input raw materials (rock phosphate, limestone and sulfur) and the output product as final fertilizer are presented and discussed.


Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation.
Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro. Strikingly, even PDX with carcinoma histology can host scarce EBV-infected B-lymphocytes that can fully overgrow carcinoma cells during serial passaging in vitro and in vivo. As serial xenografting is crucial to expand primary tumor tissue for biobanks and cohorts for preclinical mouse avatar trials, the emerging dominance of B-lymphoproliferations in serial PDX represents a serious confounding factor in these models. Consequently, repeated phenotypic assessments of serial PDX are mandatory at each expansion step to verify "bona fide" carcinoma xenografts.


Targeted delivery of maytansine to liver cancer cells via galactose-modified supramolecular two-dimensional glycomaterial.
A two-dimensional (2D) glycomaterial for targeted delivery of maytansine to liver cancer cells was developed. Host-guest interaction between a galactosyl dye and human serum albumin (HSA) produces supramolecular galactoside-HSA conjugates, which are then used to coat 2D MoS2. The 2D glycomaterial was shown to be capable of the targeted delivery of maytansine to a liver cancer cell line that highly expresses a galactose receptor, resulting in greater cytotoxicity than maytansine alone.


Brain volume and diffusion markers as predictors of disability and short-term disease evolution in multiple sclerosis.
MRI markers of neuroaxonal damage in MS have emerged as critical long-term predictors of MS-related disability. Here we investigated the potential of whole-brain diffusivity and brain volume for the prediction of cross-sectional disability and short- to medium-term clinical evolution. In this multimodal prospective longitudinal MRI study of 54 patients with MS (87% under immunomodulatory therapy, baseline and follow-up at a median of 12 months), ADC histogram analysis, WM lesion load, BPF, whole-brain atrophy rate, MSFC score, and EDSS score were obtained. A total of 44 patients with no relapse at both time points were included. At both time points, ADC histogram analysis provided robust predictors of the MSFC scores (maximal R(2) = 0.576, P < .001), incorporated cognition and fine-motor skill subscores, and EDSS scores. Significant changes beyond physiologic age-related changes at follow-up were noted for ADC histogram markers and BPF. Stronger diffusivity alterations and brain volume at baseline predicted MSFC decline, as demonstrated by multiple linear regression analysis (mean ADC, R(2) = 0.203; P = .003) and lower baseline BPF in patients with declined compared with stable MSFC scores (P = .001). Results were independent of intercurrent relapses. Diffusion histogram analysis provided stable surrogates of disability in MS and proved sensitive for monitoring disease progression during a median of 12 months. Advanced neuroaxonal pathology at baseline was indicative of an increased risk for sustained progression during a median of 12 months, independent of intercurrent relapses.