Effect of milk phospholipids on the growth and cryotolerance of lactic acid bacteria cultured and stored in acid whey-based media.
Increasing interest in foods beyond their nutritional value has promoted the development of various novel functional foods that could convey multiple health benefits to consumers. The application of lactic acid bacteria (LAB) and milk phospholipids (MPL) in combination has shown some amplifying effects on the health benefits provided by both ingredients. Freezing is commonly used in LAB preservation and storage. However, the freezing/thawing process damages cell membranes and leads to a loss in viability and functionality of LAB. This study aimed to investigate the influence of MPL on growth and cryotolerance of LAB using acid whey-based medium (AWM) supplemented with 0.5% MPL. Fourteen LAB strains were initially screened from 124 LAB using acid whey-based medium (AW). We then evaluated the cell viability and acidification ability, using the plate counting method and skim milk fermentation test, respectively, of the 14 strains cultured in AW and AWM before and after 3 cycles of freezing/thawing. The presence of 0.5% MPL in AWM significantly promoted the growth of LAB. Supplementing the culture and storage medium with 0.5% MPL significantly enhanced the resistance of selected LAB to freeze-thaw cycles in terms of cell viability and acidification ability. These results suggest that supplementing with 0.5% MPL might promote the growth of LAB and enhance the cryotolerance of LAB cultures in fermented dairy products. This finding leads to a better understanding of the synergistic effects contributed by the LAB-MPL combination and promotes the development of new LAB-MPL functional products.


Cerebrospinal fluid tau protein as a biomarker for severity of spinal cord injury in dogs with intervertebral disc herniation.
Intervertebral disc herniation (IVDH) is a common cause of spinal cord injury (SCI) in dogs. Microtubule-associated protein tau derives predominantly from neurons and axons, making it a potential marker of neuronal injury. A retrospective study, including 51 dogs with thoracolumbar or cervical IVDH and 12 clinically normal dogs, was designed to describe associations between cerebrospinal fluid (CSF) tau concentration, degree of neurological signs and motor functional recovery in dogs with IVDH. Signalment, degree of neurological dysfunction and outcome were recorded. Cisternal CSF tau values were determined by ELISA. Associations between CSF tau concentration and various clinical parameters were evaluated. Receiver-operating characteristics curve (ROC) analyses were performed to assess the validity of protein tau measurements. CSF tau concentrations were significantly higher in dogs showing plegia (median, 79.9 pg/mL; range, 0-778.7 pg/mL; P=0.016) compared to healthy dogs and dogs with paresis (median, 30.1 pg/mL; range, 0-193.1 pg/mL; P=0.025). Plegic dogs that improved by one neurological grade within 1 week had significantly lower tau protein levels compared to plegic dogs that needed more time for recovery or did not show an improvement (P=0.008). A CSF tau concentration >41.3 pg/mL had a sensitivity of 86% and specificity of 83% to predict an unsuccessful outcome in plegic dogs based on ROC analysis (area under the curve, 0.887; P=0.007, 95% confidence interval [CI] 0.717-1.057). CSF protein tau levels are positively associated with the severity of spinal cord damage and may serve as a prognostic indicator in dogs with IVDH.


Phyto-assisted synthesis of CuO/industrial waste derived biochar composite for adsorptive removal of doxycycline hydrochloride and recycling of spent biochar as green energy storage device.
The highest exposure of Endocrine disrupting compounds (EDC) into the water bodies as a result of extensive production and application of Covid-19 related drugs is a growing concern now a days. Herein, a novel nanocomposite material was developed by impregnating green synthesized copper oxide nanoparticles on the porous surface of fabric waste derived biochar to eliminate the concerned EDCs along with a sustainable disposal strategy for the spent adsorbent. Morphological characterizations by Field emission scanning electron microscopy confirmed the formation of hierarchical porous structured material. X-ray analysis revealed presence of both amorphous nature of biochar matrix as well as the crystalline nature attributed from monodispersion of copper oxide nanoparticles onto biochar surface. Batch sorption study showed removal of doxycycline hydrochloride (DOX) of >97% after 2 h at pH 7, 30 mg L-1 initial concentration of DOX and 2 g L-1 of adsorbent dose at room temperature after a two-step optimization process. Spectroscopic study and Raman shift suggested that pore filling, strong complexation and electrostatic interactions maximise the adsorption of DOX in the CuO/biochar composite as compared to the pristine biochar. However disposal of spent adsorbent is a crucial aspect for the environment and therefore, a sustainable recycling strategy for DOX loaded adsorbent as electrode material has been proposed for the first time in this study. Maximum specific capacitance value was observed in the range of 221.9-297.3 F g-1 for the DOX loaded nanocomposite at 1 mV s-1 comparable with other reported heteroatom-doped carbonaceous material as electrode. Therefore the excellent adsorption capacity of green synthesized CuO/biochar composite and its recycling after DOX adsorption can be recommended as a sustainable solution for mitigation of pharmaceuticals from wastewater. A detail study on degradation of DOX into eco-friendly products and its cost-effectiveness would be beneficial to suggest appropriate mitigation strategy for such compounds.


Auditory evoked potentials compared to performance measures and EEG in assessing excessive daytime sleepiness in narcolepsy-cataplexy.
The AEP to the repetitive stimuli of the Wilkinson auditory vigilance task was compared between untreated patients with narcolepsy-cataplexy and matched controls for periods during which the tones were preceded by 13 sec or more of wakefulness (defined by EEG-polygraphic criteria). During these periods it had been found previously that narcoleptics did not perform worse than did controls. The AEP, nevertheless, showed significant differences for narcoleptics. These were similar to changes described for drowsiness in normals. The AEP, therefore, showed changes related to excessive day time drowsines in narcolepsy-cataplexy when a sensitive performane measure and visual analysis of EEG-polygraphic recordings did not.


Assessment of the association of baseline anti-CarbV and anti-MCV antibodies with response to treatment and radiographic progression in an RA population treated with either methotrexate or baricitinib: post-hoc analyses from RA-BEGIN.
The development of autoantibodies in patients with rheumatoid arthritis (RA) has potential as a marker of treatment response. This analysis assessed the association of an autoantibody response to carbamylated vimentin (anti-CarbV) and to vimentin modified by citrullination (anti-MCV) with response to treatment and structural damage progression in the phase III study RA-BEGIN. Data from patients in the modified intent-to-treat population of RA-BEGIN were included for analysis; these patients received methotrexate (MTX), baricitinib 4 mg once daily, or baricitinib plus MTX during the 52-week study period. Endpoints analyzed were clinical response to treatment, assessed using change from baseline (CFB) in Simplified Disease Activity Index (SDAI) and Disease Activity Score for 28-joint count with serum high-sensitivity C-reactive protein (DAS28-hsCRP), and structural damage progression, assessed using CFB greater than the smallest detectable change in the van der Heijde-modified Total Sharp Score. The anti-CarbV and anti-MCV isotypes assessed were immunoglobulin (Ig) A, IgG, and IgM. Multivariable mixed-effect models for repeated measures (MMRMs) were used for the longitudinal analysis of treatment response, and multivariable logistic regression models were used for the analysis of structural damage progression at week 52. Analysis of the association between autoantibodies and treatment response showed that high titers of anti-CarbV (IgA and IgG) were associated with a greater clinical response as measured by SDAI and DAS28-hsCRP. Anti-CarbV IgA and IgG, but not IgM, demonstrated an association after adjustment for other factors included in the MMRMs. High titers of anti-CarbV IgM were associated with a poor response to MTX monotherapy, whereas a nonsignificant trend toward a better response to baricitinib and baricitinib plus MTX was observed. There was no association between anti-MCV antibodies and treatment response. High titers of anti-CarbV IgA were associated with a greater probability of radiographic progression, but no association between anti-MCV antibodies and radiographic progression was observed. High titers of anti-CarbV IgA and IgG isotypes, but not anti-MCV isotypes, may be useful prognostic biomarkers for identifying the likelihood of the response to treatment and structural damage progression in patients with RA.


Psychological distress among first-year health science students in Taiwan.
Most first-year college/university students are adolescents or young adults and therefore are at high risk of developing psychological distress symptoms. Little is known about psychological distress among first-year university students in Taiwan, especially those studying health science-related fields. To understand the prevalence of psychological distress and its five dimensions (depression and anxiety, self-harm, impulsivity, and psychiatric disturbance) and explore the relationship between student-specific variables (enrollment year, age, sex, program duration, and college) and psychological distress. A secondary analysis design was adopted. We enrolled 4,212 first-year university students throughout 2016, 2017, and 2018. Health screening data were obtained using the Mental Health Scale for Undergraduate-Screening Assessment (MHSU-SA) for first-year health science students at a private technical-vocational university in northern Taiwan. Many first-year university students were at-risk for depression (4.2%), anxiety (8.2%), self-harm (5.2%), impulsivity (2.6%), psychiatric disturbance (4.4%), and overall psychological distress (4.2%). Students in a four-year program were more than twice as likely to demonstrate psychological distress symptoms compared to their two-year (night) program counterparts (odds ratio = 2.05, 95% confidence interval = 1.20-3.49, p < 0.01). Some first-year health science university students showed psychological distress, including anxiety, self-harm, psychiatric disturbance, depression, and impulsivity. Students in four-year programs were twice as likely to show symptoms of psychological distress than those in two-year (night) programs. Therefore, mental health screenings are recommended to facilitate early detection and timely intervention for at-risk students.


β-Carboline dimers inhibit the tumor proliferation by the cell cycle arrest of sarcoma through intercalating to Cyclin-A2.
β-Carbolines are potentially strong alkaloids with a wide range of bioactivities, and their dimers exhibit stronger antitumor activity other than the monomers. However, the detailed mechanisms of the β-carboline dimers in inhibiting sarcoma (SARC) remain unclear. The results showed that β-carboline-3-carboxylic acid dimers Comp1 and Comp2, which were synthesized in our lab and modified at the N9 position and linked at the C3 position, exhibited effective inhibition activity on MG-63 proliferation (IC50 = 4.6μM). Meanwhile, the large scale transcriptome profiles of SARC from The Cancer Genome Atlas (TCGA) were analyzed, and found that abnormal expression of genes relevant to apoptosis, cell cycle, and signaling pathways of Hedgehog, HIF, Ras involved in the SARC pathogenesis. Interestingly, both dimers could promote the apoptosis and arrest the cell cycle in S phase to inhibit proliferation of MG-63. Moreover, Comp1 and Comp2 inhibited the expression CDK2, CCNA2, DBF4, and PLK1 associated with various immune cells and cell cycle in MG-63. Remarkably, drug-target interaction network analysis showed that numerous proteins involved in cell cycle were the potential targets of Comp1 and Comp2, especially CCNA2. Further molecular docking, isothermal titration calorimetry (ITC) and Cellular Thermal Shift Assay (CETSA) confirmed that both dimers could directly interact with CCNA2, which is significantly correlated with CD4+ T cells, by strong hydrophobic interactions (Kd=5.821 ×106 N). Meanwhile, the levels of CCNA2 and CDK2 were inhibited to decrease in MG-63 by both dimer treatments at transcription and protein levels, implying that Comp1 and Comp2 blocked the interaction between CCNA2 and CDK2 through competitive binding with CCNA2 to arrest the cell cycle of MG-63 cells in the S phase. Additionally, the transcriptome profiles of β-carboline-treated mice from Gene Expression Omnibus (GEO) were obtained, and found that similar antitumor mechanism was shared among β-carboline derivatives. Overall, our results elucidated the antitumor mechanisms of Comp1 and Comp2 through dual-suppressing the function of CCNA2 to profoundly arrest cell cycle of MG-63, then effectively inhibited cell proliferation of MG-63. These results provide new insights into the antitumor mechanism of β-carboline dimers and new routes of various novel cancer-related drug targets for future possible cancer therapy.


[Metabolic syndrome and hormone profile in patients with erectile dysfunction].
To demonstrate the existence of relation between metabolic syndrome and erectile dysfunction and to analyze the hormone profile of these patients regarding a healthy population group. A case-control study was designed with 65 men divided into 2 groups according to presence or non-presence of erectile dysfunction. Group A was made up of 37 men with erectile dysfunction and group B by 28 healthy men without erectile dysfunction. Ages ranged from 40 to 65 years. The presence of metabolic syndrome according to the ATPIII definition, performance of physical exercise, smoking habit, body mass index and complete hormone profile including testosterone -total, free and bioavailability, were studied. Greater presence of metabolic syndrome was detected among men of Group A (72.9%) versus those of group B (17.8%) (p=0.0001). Among the parameters that make up the metabolic syndrome, there are differences between both groups in systolic and diastolic blood pressure, fast blood sugar and abdominal circumference, all these differences being significant. After performing multivariate analysis between the metabolic syndrome and erectile dysfunction adjusted for age, BMI, International Index for Erectile Function (IIEF), physical exercise and smoking habit, we have observed an independent significant relation between the metabolic syndrome and erectile dysfunction. We have not found differences between both groups in any hormone parameter. A relationship is found between metabolic syndrome and erectile dysfunction. Thus, it seems recommendable to perform the metabolic profile and cardiovascular risk study in these patients.


[Smoking prevalence in Portuguese school-aged adolescents by gender: can we be optimistic?].
According to the MPOWER approach adopted in 2008 by the WHO, monitoring smoking epidemics is necessary in order to assess the effectiveness of the preventive measures used in smoking control in adolescents and adults. To determine the prevalence of smoking in Portuguese school-aged adolescents by region. The sample is made up of 8764 students, 4060 boys and 4704 girls, and is representative of the Portuguese students in regular public education. The data was collected in the 2008/2009 academic year, through a quantitative self-report questionnaire. In the total sample, 10.2% of boys and 9.1% of girls are regular smokers. Smoking increases with age. At 15 years old 12.3% of the boys and 8.6% of the girls are regular smokers and 6.1% of the boys and 4.0% of the girls are occasional smokers. Looking at prevalence by region, the highest prevalence of regular smoking is found in Alentejo (14.7%), followed by Azores (11.8%) and the lowest is found in Algarve (4.1%). The prevalence of smokers among Portuguese school-aged adolescents varies within the several regions of the country, similar to what happens in the adult Portuguese population.


Drug and alcohol use among patients with schizophrenia and related psychoses: levels and consequences.
Patients with schizophrenia and related psychoses frequently use, abuse and become dependent on psychoactive substances. Local surveys indicate differences in both types and patterns of substances used. A cross-sectional survey was conducted to document abuse in 207 successive outpatients presenting to a psychiatric continuing care facility in a large Canadian city. Nicotine, alcohol and cannabis were the most frequently abused substances in the cohort. Excluding nicotine, 44.9% met criteria for lifetime and 14.0% for current abuse/dependence. Cocaine, heroin, hallucinogen, amphetamine, and inhalant use were rarely reported. Patients with current substance abuse/dependence and a psychotic disorder (dual diagnosis, DD) had significantly higher Positive and Negative Symptom Scale (PANSS) positive scores than lifetime-DD or those with a single diagnosis (SD). Significantly more current-DD (69.0%) patients were depressed (HAM-D score > or =12) compared to SD (45.6%). Furthermore, current-DD (27.6%) patients were more likely than SD (4.5%) to be medication non-compliant. Patients with current-DD were more likely to smoke cigarettes (88.9%) compared to those with SD (49.6%) and they had significantly longer histories of cigarette smoking (19.1 for DD vs. 11.5 years for SD). The smoking behavior of the DD population is discussed in terms of enhanced risk for alcohol abuse, as well as effects on antipsychotic blood levels and metabolism.


Barley long non-coding RNAs (lncRNA) responsive to excess boron.
Long non-coding RNA (lncRNA) has a misleading name, since although they do not encode proteins, they may encode small peptides. Such transcripts are emerging as regulatory molecules. With the advent of next-generation sequencing technologies and novel bioinformatics tools, a tremendous amount of lncRNAs have been identified in several plant species. Recent reports demonstrated roles of plant lncRNAs such as development and environmental response. Here, we reported a genome-wide discovery of ~8000 barley lncRNAs and measured their expression pattern upon excessive boron (B) treatment. According to the tissue-based comparison, leaves have a greater number of B-responsive differentially expressed lncRNAs than the root. Functional annotation of the coding transcripts, which were co-expressed with lncRNAs, revealed that molecular function of the ion transport, establishment of localization, and response to stimulus significantly enriched only in the leaf. On the other hand, 32 barley endogenous target mimics (eTM) as lncRNAs, which potentially decoy the transcriptional suppression activity of 18 miRNAs, were obtained. Also, six lncRNAs, differentially expressed upon B-treatment, were selected and quantitatively analyzed in both B-sensitive and B-tolerant cultivars treated by excess B-level. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed the B-responsive expressional changes obtained by RNA sequencing. Notably, some lncRNAs (i.e., TCONS_00045190 and TCONS_00056415) over-expressed only in B-tolerant cultivar upon excess B treatment. Presented data including identification, expression measurement, and functional characterization of barley lncRNAs suggest that B-stress response might also be regulated by lncRNA expression, via cooperative interaction of miRNA-eTM-coding target transcript modules.


Industrial medicine and acute musculoskeletal rehabilitation. 2. Acute cervical spine and shoulder injuries in the industrial setting.
This self-directed learning module highlights the underlying anatomy and biomechanics of the cervical spine and shoulder as a basis for developing a differential diagnosis of contributing pathology in an industrial injury. This includes components of the history, examination, and appropriate diagnostic testing that are necessary to develop an optimal rehabilitation plan. Treatment options are reviewed and include medications, therapy, selective injections, and return-to-work programs in the industrial setting. (a) To be able to identify neck and shoulder pathology, (b) to effectively evaluate cervical spine and shoulder injuries, and (c) to rehabilitate acute cervical spine and shoulder injuries in the industrial setting.


Ultrastaging of early colon cancer using lymphatic mapping and molecular analysis.
Approximately one-third of node-negative colon cancers will recur, possibly due to understaging and inadequate pathological examination of lymph nodes (LNs). We evaluated the sensitivity, accuracy and feasibility of staging based on lymphatic mapping, focused examination, and molecular analysis of the sentinel node (SN) in patients with primary colorectal carcinoma. Between 1996 and 2000, 100 patients with colon carcinoma (CRC) underwent lymphatic mapping immediately after peritumoral injection of 1.0 cc of isosulphan blue dye. All LNs in the CRC specimen were examined by routine haematoxylin and eosin (H&E) staining. Sentinel nodes were examined by step serial sectioning, cytokeratin immunohistochemistry (CK-IHC) and/or reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in an attempt to identify occult micrometastatic disease. Lymphatic mapping was successful in 97% of the cases. There were 5 false-negative cases, predominately associated with T3/T4 tumours. Aberrant lymphatic drainage was identified in 8 patients (8%) altering the operative approach. 26 patients had H&E-positive LNs. In 74 patients who were node-negative by routine H&E, 18 (24%) had occult nodal micrometastases missed on routine H&E examination, but detected by focused analysis of the SN. RT-PCR analysis of the SN was performed in 40 patients, 26 of which were negative by H&E and CK-IHC. In 12/26 (46%) of these patients, there was additional evidence of micrometastatic disease. In this study, focused examination of the SN in conjunction with RT-PCR analysis identified micrometastatic disease in a significant number of node-negative patients. This may have important implications when selecting patients for adjuvant treatment protocols.


Confluence-Induced Squamous Differentiation Is Not Accompanied by Changes in H3K27me3 Repressive Epigenetic Mark.
Recent studies have reported that epigenetic mechanisms may regulate the initiation and progress of squamous differentiation in normal and transformed keratinocytes. In particular, the role of the repressive H3K27me3 mark in the regulation of squamous differentiation has been prominent. However, there is conflicting literature showing that squamous differentiation may be dependent upon or independent of changes in H3K27me3 status. In this study we have examined the binding of trimethylated H3K27 to the promoters of proliferation or differentiation genes in keratinocytes undergoing squamous differentiation in vitro and in vivo. Initially, we examined the expression levels for EZH1, EZH2, and H3K27me3 in differentiating keratinocytes in vitro and in vivo. We extended this to include H3K27me3 chromatin immunoprecipitation sequencing (ChIP-seq). Based on these studies, we could find no evidence for an association between widespread gain or loss of H3K27me3 on the promoters of proliferation-specific or differentiation-specific target genes, respectively, during squamous differentiation in adult human keratinocytes. These data suggest that squamous differentiation may occur independent of regulation by H3K27me3 on proliferation and differentiation genes of normal adult human keratinocytes.


Design, synthesis and biological evaluation of novel beta-substituted indol-3-yl ethylamido melatoninergic analogues.
A series of new melatonin analogues have been synthesized. Interestingly, two of the new compounds, 11c and 11e, which did not show any appreciable affinity for the melatonin receptor, were found to be potent inhibitors of lipid peroxidation in rat liver microsomes. Analogue 11c, in particular, is a better antioxidant than melatonin.


Coenzyme Q10: a new drug for myocardial ischemia?
A biochemical rationale for using CoQ in treating certain cardiovascular diseases has been established. CoQ subserves an endogenous function as an essential cofactor in several metabolic pathways, particularly oxidative respiration. As an exogenous source in supraphysiologic doses, CoQ may have pharmacologic effects that are beneficial to tissues rendered ischemic and then reperfused. Its mechanism of action appears to be that of a free radical scavenger and/or direct membrane stabilizer. Initial clinical studies performed abroad and in the United States indicate that CoQ may be effective in treating certain patients with ischemic heart disease, congestive heart failure, toxin-induced cardiotoxicity, and possibly hypertension. The most intriguing property of CoQ is its potential to protect and preserve ischemic myocardium during surgery. Currently, CoQ is still considered an experimental agent and only further studies will determine whether it will be useful therapy for human cardiovascular disease states.


Decidual prolactin-related protein. Identification, molecular cloning, and characterization.
In this report, we describe the isolation, molecular cloning, and characterization of a new member of the prolactin (PRL)-growth hormone (GH) family expressed in rat decidual tissue. A 29-kDa protein was isolated from medium conditioned by decidual explants. The protein possessed an affinity for concanavalin A and cross-reactivity with antibodies to two rat placental proteins, PRL-like protein-B (PLP-B) and PLP-C and with antibodies to human PRL. NH2-terminal sequencing of the isolated decidual protein indicated that it shared significant sequence identity with the NH2 terminus of PLP-C. The decidual protein was termed decidual prolactin-related protein (dPRP). A PLP-C cDNA was used to identify dPRP cDNAs from a rat decidual cDNA library. Nucleotide sequence analyses of the dPRP cDNAs predicted a mature protein of 239 amino acids, including a 28-amino acid signal sequence. The predicted dPRP amino acid sequence contains two putative N-linked glycosylation sites and 6 cysteine residues. The 6 cysteines are located in positions homologous to the cysteines of PLP-C and PRL. Additional sequence similarities with members of the PRL-GH family are evident. The dPRP gene was localized to rat chromosome 17, which also carries other members of the PRL gene family. Northern blot analysis showed that the dPRP cDNA clone specifically hybridized to a 1.0-kilobase mRNA. The relationship of dPRP with other members of the PRL-GH family and its putative role(s) in the physiology of pregnancy are discussed.


Retrospective Diagnosis of Ataxia-Telangiectasia in an Adolescent Patient With a Remote History of T-Cell Leukemia.
Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder characterized by progressive cerebellar degeneration that is typically diagnosed in early childhood. A-T is associated with a predisposition to malignancies, particularly lymphoid tumors in childhood and early adulthood. An adolescent girl with minimal neurologic symptoms was diagnosed with A-T 8 years after completing therapy for T-cell acute lymphoblastic leukemia, following a diagnosis of ATM-mutated breast cancer in her mother. We highlight the importance of recognizing ATM mutations in T-cell acute lymphoblastic leukemia, appreciating the phenotypic heterogeneity of A-T, and defining optimal cancer screening in A-T patients.


Critical review on chemical compositions and health-promoting effects of mushroom Agaricus blazei Murill.
Agaricus blazei Murrill (AbM) is a medical mushroom which has huge potential commercial value with various health-promoting functions. However, the chemical composition and therapeutic mechanisms of AbM have not been concluded systematically yet. Thus, this study aims to comprehensively summarize the phytochemical profiles and thoroughly characterize the health promotion effects such as the antitumor and antidiabetic impact of AbM in in vivo and in vitro. The AbM consists of abundant bioactive substances; polysaccharides, lipids including ergosterol, sterols, proteins, vitamin B, C and D, and phenolic compounds. Several studies have claimed that Agaricus blazei Murrill polysaccharides (AbMP) had immunoregulation, anti-inflammatory, hepatoprotective, and antitumor function both in vivo and in vitro. Meanwhile, AbM extracts were thought to cure diabetes and bacterial infection, exhibiting anticarcinogenic and antimutagenic functions. But some principles behind health-promoting effects have not been clarified. Additionally, AbM related clinical trials are limited and further discovery need to be conducted. Therefore, this paper has concluded the health promotion impact with corresponding mechanisms of AbM and indicated its potential medical usage as functional food in the future.


Rheumatoid arthritis as a hyper-endoplasmic-reticulum-associated degradation disease.
We introduce Synoviolin as a novel pathogenic factor in rheumatoid arthritis (RA). Experimental studies indicate that this endoplasmic reticulum (ER)-resident E3 ubiquitin ligase has important functions in the ER-associated degradation (ERAD) system, an essential system for ER homeostasis. Overexpression of Synoviolin in mice causes arthropathy with synovial hyperplasia, whereas heterozygous knockdown results in increased apoptosis of synovial cells and resistance to collagen-induced arthritis in mice. On the basis of these experimental data, we propose that excess elimination of unfolded proteins (that is, 'hyper-ERAD') by overexpression of Synoviolin triggers synovial cell overgrowth and hence a worsening of RA. Further analysis of the hyper-ERAD system may permit the complex pathomechanisms of RA to be uncovered.


Food poisoning outbreak in Tokyo, Japan caused by Staphylococcus argenteus.
Staphylococcus argenteus is a novel species subdivided from Staphylococcus aureus. Whether this species can cause food poisoning outbreaks is unknown. This study aimed to investigate the enterotoxigenic activities of two food poisoning isolates suspected to be S. argenteus (Tokyo13064 and Tokyo13069). The results for phylogenic trees, constructed via whole genome sequencing, demonstrated that both isolates were more similar to a type strain of S. argenteus (MSHR1132) than any S. aureus strain. Moreover, the representative characteristics of S. argenteus were present in both strains, namely both isolates belong to the CC75 lineage and both lack a crtOPQMN operon. Thus, both were determined to be "S. argenteus." The compositions of the two isolates' accessory elements differed from those of MSHR1132. For example, the seb-related Staphylococcus aureus pathogenicity island, SaPIishikawa11, was detected in Tokyo13064 and Tokyo13069 but not in MSHR1132. Both isolates were suggested to belong to distinct lineages that branched off from MSHR1132 lineages in terms of accessory elements. Tokyo13064 and Tokyo13069 expressed high levels of s(arg)eb and produced S(arg)EB protein, indicating that both have the ability to cause food poisoning. Our findings suggest that S. argenteus harboring particular accessory elements can cause staphylococcal diseases such as food poisoning, similarly to S. aureus.


Overview of Immunodeficiency Disorders.
The spectrum of primary immunodeficiency disorders (PIDs) is expanding. It includes typical disorders that primarily present with defective immunity as well as disorders that predominantly involve other systems and show few features of impaired immunity. The rapidly growing list of new immunodeficiency disorders and treatment modalities makes it imperative for providers to stay abreast of the latest and best management strategies. This article presents a brief overview of recent clinical advances in PIDs.


Calibration of the NPL secondary standard radionuclide calibrator for 125I seeds used for prostate brachytherapy. National Physical Laboratory.
In the therapeutic use of radionuclides, by far the most rapid growth in recent years is that of 125I seeds used for the treatment of prostate cancer. Large numbers of these seeds are used in each treatment and there is a need for a simple but accurate means of confirming their dose rates. This mechanism requires a transfer device for which the calibration factors are traceable to national standards. The NPL secondary standard radionuclide calibrator, because of its guaranteed reproducibility and traceable calibration procedure, is ideally suited for this purpose. A series of characterisation measurements have been performed on the NPL radionuclide calibrator in order to estimate the uncertainty levels that can be achieved and these are presented together with the relevant calibration factors for some typical seeds.


Haloperidol-induced plasticity of axon terminals in rat substantia nigra.
An electron micrographic morphometric analysis of nerve endings in substantia nigra of rats repeatedly treated with haloperidol was performed. Although most parameters showed no difference, drug-treated animals exhibited a significant shift in the distribution of relative numbers of axon terminals, suggesting neuroleptic-induced axon-collateral sprouting.


Health promotion perspectives on the COVID-19 pandemic: The importance of religion.
In this article we examine the importance of religion for COVID-19 health promotion. We advance three main arguments. First, religion plays an important role in affecting how likely it is that people will become infected with COVID-19. Second, religion should not be seen as a 'problem' with regards to COVID-19 but as an important part of the worldview and lifestyle of many people. Third, there are valuable health promotion lessons we can learn not only from the intersection of religion and other infectious diseases, but also from approaches taken within science education. Contentious science topics such as evolution and vaccine hesitancy have been effectively communicated to those with a religious faith who are disposed to reject them by reframing and considering religion as a worldview and treating those who do not accept standard scientific theories sensitively. Religion has much to contribute to health promotion, including introducing perspectives on life's meaning and on death that can differ from those held by many without religious faith. Furthermore, religious leaders are important gatekeepers to their communities and can therefore play a vital role in policy implementation, even when that policy makes no overt reference to religion. Our contention is that by working with those of faith in the context of COVID-19, health promotion can be enhanced.


[Management of bleeding esophageal varices in public and private institutions in Chile].
The better treatment modalities for bleeding esophageal varices have improved the prognosis of cirrhosis. To inquire about diagnostic and treatment modalities for esophageal bleeding in Chile. An enquiry about diagnosis and treatment of esophageal bleeding was designed and electronically sent to public and private health institutions that could admit patients and were located in cities with more than 100,000 inhabitants. The enquiry was answered by 31 of 35 public and 17 of 19 private health institutions that were consulted. Emergency endoscopy was available in 6 of 27 public and in the 16 private institutions that had an emergency room. Rubber band was available in 16 public (52%) and in all private institutions. Cyanoacrylate injections were done in 10 public (32%) and 11 (65%) private institutions. No public institution installed transjugular intrahepatic portosystemic shunts, but 8 had occasional access to this technique. This procedure was done in 7 (41%) private institutions and all had access to it. Surgical treatment was feasible in 20 public (65%) and all private institutions. Primary prophylaxis was done in 18 public (58%) and 14 private (82%) institutions. Secondary prophylaxis was carried out in 26 public (84%) and 16 private (94%) institutions. Public health institutions have poor access to adequate diagnostic and treatment methods for esophageal bleeding. The primary and secondary prophylaxis of esophageal varices must be improved in both types of institutions.


Evaluation and treatment of acute bleeding from the head and neck.
Three entities that can cause life threatening bleeding in the head and neck are described: epistaxis, post-tonsillectomy bleeding, and post-tracheostomy bleeding. It behooves all physicians operating in this area and emergency room physicians and personnel to be acquainted with the diagnosis and management of these situations.


Effects of castration, steroid replacement, and sexual experience on mesolimbic dopamine and sexual behaviors in the male rat.
The concentrations of dopamine (DA) and a DA metabolite in a terminal field of the mesolimbic DA system, the nucleus accumbens, decreased after castration, an effect that was prevented by treatment with testosterone (T) or estradiol. After castration, DA concentrations were increased in the medial preoptic area, and were unchanged in the caudate-putamen, substantia nigra, and ventral tegmental area. Changes in DA and DA metabolite concentrations in the nucleus accumbens coincided with changes in measures of sexual arousal. Sexual experience did not affect DA concentrations, but did increase DA metabolism in the nucleus accumbens, and also increased the frequency of female-directed behavior in castrated males. These results suggest that T, or its aromatized metabolite, influences the mesolimbic DA system, and that this system is involved in mediating sexual arousability.


Potential value and chemical characterization of gut microbiota derived nitrogen containing metabolites in feces from Periplaneta americana (L.) at different growth stages.
The American cockroach, Periplaneta americana (L.), is able to highly survive in various complicated environments around the globe, and often considered as a pest. In contrast, billions of P. americana have been massively reared in China and extensively used as a medicinal insect, due to its function for preventing and treating ulceration and heart failure. Considering the possibility that microbiota-derived metabolites could be an effective source to identify promising candidate drugs, we attempted to establish a rapid method for simultaneous determination of gut microbiota metabolites from medicinal insects. In this study, network pharmacology approach and ultra-performance liquid chromatography (UPLC) technique were employed to reveal the potential pharmacological activity and dynamics variation of nitrogen-containing metabolites (NCMs) originated from the gut microbiota of breeding P. americana at different growth stages. A metabolites-targets-diseases network showed that NCMs are likely to treat diseases such as ulceration and cancer. The analysis of NCMs' content with the growth pattern of P. americana indicated that the content of NCMs declined with P. americana aging. Both principal component analysis and orthogonal partial least squares discriminant analysis suggested that 8-hydroxy-2-quinolinecarboxylic acid and 8-hydroxy-3,4-dihydro-2(1H)-quinolinone are the potential differential metabolic markers for discriminating between nymphs and adults of P. americana. Moreover, the developed UPLC method showed an excellent linearity (R2 > 0.999), repeatability (RSD < 2.6%), intra- and inter-day precisions (RSD < 2.2%), and recovery (95.5%-99.0%). Collectively, the study provides a valuable strategy for analyzing gut microbiota metabolites from insects and demonstrates the prospects for discovering novel drug candidates from the feces of P. americana.


Common skin infection due to Panton-Valentine leucocidin-producing Staphylococcus aureus strains in asylum seekers from Eritrea: a genome-based investigation of a suspected outbreak.
Since late 2014, multiple cases of abscesses and boils due to methicillin-susceptible Staphylococcus aureus (MSSA) expressing the Panton-Valentine leucocidin (PVL) were observed in Eritrean asylum seekers in Lausanne, Switzerland. Strains isolated from infected Eritrean and non-Eritrean patients were compared by whole genome sequencing to determine whether these numerous cases result from an outbreak. The genome of S. aureus PVL-producing strains were sequenced and compared. Clinical and epidemiological characteristics of patients infected by PVL-producing strains were investigated. This work reports 15 cases of infections due to PVL-producing strains affecting mostly asylum seekers (n = 10), people working with refugees and/or exposed to Africans (n = 3). Most infections were due to closely related strains of CC152 (n = 8) and CC15 (n = 3), two distantly related (>34 000 core single nucleotide polymorphisms) clonal complexes. An epidemiological link between the 15 cases could be ruled out by whole genome sequencing (33 to 172 core single nucleotide polymorphisms between the different strains of a given complex). Altogether, these results reflect the probable high incidence of CC15 and CC152 PVL-producing strains in eastern Africa. Clinicians facing unusual skin infections in African refugees (or in any person returning from this region of high endemicity) should consider S. aureus PVL-producer before suspecting rare infections such as leishmaniasis or rickettsiosis. Clinicians should also remember that PVL are frequently expressed by MSSA in some regions of the world and that antibiotics that are efficient on toxin expression, such as clindamycin, represent the best therapeutic option.


Conversion of human cardiac progenitor cells into cardiac pacemaker-like cells.
We used a screening strategy to test for reprogramming factors for the conversion of human cardiac progenitor cells (CPCs) into Pacemaker-like cells. Human transcription factors SHOX2, TBX3, TBX5, TBX18, and the channel protein HCN2, were transiently induced as single factors and in trio combinations into CPCs, first transduced with the connexin 30.2 (CX30.2) mCherry reporter. Following screens for reporter CX30.2 mCherry gene activation and FACS enrichment, we observed the definitive expression of many pacemaker specific genes; including, CX30.2, KCNN4, HCN4, HCN3, HCN1, and SCN3b. These findings suggest that the SHOX2, HCN2, and TBX5 (SHT5) combination of transcription factors is a much better candidate in driving the CPCs into Pacemaker-like cells than other combinations and single transcription factors. Additionally, single-cell RNA sequencing of SHT5 mCherry+ cells revealed cellular enrichment of pacemaker specific genes including TBX3, KCNN4, CX30.2, and BMP2, as well as pacemaker specific potassium and calcium channels (KCND2, KCNK2, and CACNB1). In addition, similar to human and mouse sinoatrial node (SAN) studies, we also observed the down-regulation of NKX2.5. Patch-clamp recordings of the converted Pacemaker-like cells exhibited HCN currents demonstrated the functional characteristic of pacemaker cells. These studies will facilitate the development of an optimal Pacemaker-like cell-based therapy within failing hearts through the recovery of SAN dysfunction.


Transcriptome analysis and histopathology of the mud crab (Scylla paramamosain) after air exposure.
The mud crab, Scylla paramamosain, is an economically-important crab in China. Air exposure is an important environmental stressor during mud crab culture and transportation. Adaptive mechanisms responding to air exposure in mud crabs are still poorly understood. In this study, mud crabs were exposed to air for 120 h. Air exposure decreased total hemocyte counts, led to cytological damage, and caused high mortality. Transcriptomic analysis was conducted at 0, 6 and 96 h after air exposure. A total of 3530 differentially expressed genes (DEGs) were identified. DEGs were mainly involved in the oxidative stress response, metabolism, cellular processes, signal transduction, and immune functions. Transcriptomic analysis also revealed that genes of glycolysis and of the tricarboxylic acid cycle were key factors in regulating the mud crab adaptation to air exposure.


A new perfusion chamber to detect platelet adhesion using a small volume of blood.
Perfusion studies with human blood are traditionally performed in relatively large chambers (10x 0.6 mm) through which blood is circulated at 55 mL/min to achieve a shear rate (s.r.) of 1600/sec. A volume of 15 mL is sometimes used which means the blood is recirculated up to 20 times through the chamber during a standard perfusion of five minutes. We have developed a new chamber of much smaller dimensions (5x0.1 mm) through which blood is drawn with a syringe pump at a velocity of 0.3 mL/min for a s.r. of 1600/sec. This chamber has the advantage that little platelet activation occurs during perfusion. Smaller quantities of inhibitors or antibodies are required and it is possible to perform several perfusions with native blood from a single patient. The setup, advantages and disadvantages of the system are described. A modification of the same chamber has been used for the direct observation and quantitation of the adhesion of neutrophils and monocytes to platelets and/or fibrin under flow. Platelet adhesion under flow has also been studied with direct observation using this same chamber.


Publishing on the WWW. Part 4 - Pubmed Central: a publishing paradigm shift.
This article discusses the environment leading to the founding of the Pubmed Central database, and its likely effects on publishing as we know it.


Overexpression of human NOX1 complex induces genome instability in mammalian cells.
The production of reactive oxygen species (ROS) in mammalian cells is tightly regulated because of their potential to damage macromolecules, including DNA. To investigate possible links between high ROS levels, oxidative DNA damage, and genomic instability in mammalian cells, we established a novel model of chronic oxidative stress by coexpressing the NADPH oxidase human (h) NOX1 gene together with its cofactors NOXO1 and NOXA1. Transfectants of mismatch repair (MMR)-proficient HeLa cells or MMR-defective Msh2(-/-) mouse embryo fibroblasts overexpressing the hNOX1 complex displayed increased intracellular ROS levels. In one HeLa clone in which ROS were particularly elevated, reactive nitrogen species were also increased and nitrated proteins were identified with an anti-3-nitrotyrosine antibody. Overexpression of the hNOX1 complex increased the steady-state levels of DNA 8-oxo-7,8-dihydroguanine and caused a threefold increase in the HPRT mutation rate in HeLa cells. In contrast, additional oxidatively generated damage did not affect the constitutive mutator phenotype of the Msh2(-/-) fibroblasts. Because no significant changes in the expression of several DNA repair enzymes for oxidative DNA damage were identified, we suggest that chronic oxidative stress can saturate the cell's DNA repair capacity and cause significant genomic instability.


Minimizing toxic chlorinated byproducts during electrochemical oxidation of Ni-EDTA: Importance of active chlorine-triggered Fe(II) transition to Fe(IV).
The formation of chlorinated byproducts represents a significant threat to the quality of the effluent treated using electrochemical advanced oxidation processes (EAOPs), thus spurring investigation into alleviating their production. This study presents a new strategy to minimize the release of chlorinated intermediates during the electrochemical oxidation of Ni-EDTA by establishing a dual mixed metal oxide (MMO)/Fe anode system. The results indicate that the dual-anode system achieved a substantially higher rate (0.141 min-1) of Ni-EDTA destruction and accordingly allowed a more pronounced removal of aqueous Ni (from 39.85 to 0.63 mg L-1) after alkaline precipitation, compared with its single MMO anode (0.017 min-1 of Ni-EDTA removal, with 14.38 mg L-1 Ni remaining) and single Fe anode (insignificant Ni-EDTA removal, with 38.37 mg L-1 Ni remaining) counterparts. Compared to reactive chlorine species (RCS) produced from the single MMO anode system, Fe(IV) was in situ generated from the dual-anode system and was predominantly responsible for the attenuation of chlorinated byproducts and thus the decrease in the acute toxicity of the treated solution (evaluated using luminescent bacteria). The Fe(IV)-dominated dual-anode system also exhibited superior performance in removing multiple pollutants (including organic ligands, Ni, and phosphite) in the real electroless plating effluent. The findings suggest that the strategy for Fe(II) transition to Fe(IV) by active chlorine paves a new avenue for yielding less chlorinated products with lower toxicity when EAOPs are used to treat chloride-containing organic wastewater.


The importance of the social and intellectual contexts in a discussion of the history of the concept of psychosis.
This paper show that, through out its 150 year history, the concept of 'psychosis' has not been static, but has reflected the intellectual and social contexts in which it has been employed. Initially the concept reflected the Romantic psychiatrists' emphasis on the whole personality. With the advent of materialism the concept was applied to all mental disorders. Because of the claims for organic cerebral findings in dementia praecox, it was described by Meyer as fitting the disease concept, with characteristic pathology, symptomatology, course and prognosis. However, the different social milieux of patients being treated by psychiatrists such as Kraepelin and Bonhoeffer led to different emphases regarding the aetiology of the psychoses. In the later twentieth century the influence of urbanization in Europe and Africa and also the rise of Nazism led to changes in relation to the use of the concept of psychosis.


Phylogenetically related Argentinean and Australian Escherichia coli O157 isolates are distinguished by virulence clades and alternative Shiga toxin 1 and 2 prophages.
Shiga toxigenic Escherichia coli O157 is the leading cause of hemolytic uremic syndrome (HUS) worldwide. The frequencies of stx genotypes and the incidences of O157-related illness and HUS vary significantly between Argentina and Australia. Locus-specific polymorphism analysis revealed that lineage I/II (LI/II) E. coli O157 isolates were most prevalent in Argentina (90%) and Australia (88%). Argentinean LI/II isolates were shown to belong to clades 4 (28%) and 8 (72%), while Australian LI/II isolates were identified as clades 6 (15%), 7 (83%), and 8 (2%). Clade 8 was significantly associated with Shiga toxin bacteriophage insertion (SBI) type stx(2) (locus of insertion, argW) in Argentinean isolates (P < 0.0001). In Argentinean LI/II strains, stx(2) is carried by a prophage inserted at argW, whereas in Australian LI/II strains the argW locus is occupied by the novel stx(1) prophage. In both Argentinean and Australian LI/II strains, stx(2c) is almost exclusively carried by a prophage inserted at sbcB. However, alternative q(933)- or q(21)-related alleles were identified in the Australian stx(2c) prophage. Argentinean LI/II isolates were also distinguished from Australian isolates by the presence of the putative virulence determinant ECSP_3286 and the predominance of motile O157:H7 strains. Characteristics common to both Argentinean and Australian LI/II O157 strains included the presence of putative virulence determinants (ECSP_3620, ECSP_0242, ECSP_2687, ECSP_2870, and ECSP_2872) and the predominance of the tir255T allele. These data support further understanding of O157 phylogeny and may foster greater insight into the differential virulence of O157 lineages.


Elevated preoperative von Willebrand factor is associated with perioperative thrombosis in infants and neonates with congenital heart disease.
Essentials Perioperative thrombosis is a major cause of morbidity and mortality in congenital heart disease. Neonates and infants undergoing repair of congenital heart lesions were prospectively followed. Elevated von Willebrand factor (VWF) to ADAMTS-13 activity ratios typified the postoperative period. Thrombosis was associated with preoperative VWF activity and cryoprecipitate transfusion SUMMARY: Background The surgical repair of congenital heart malformations is frequently complicated by perioperative thrombosis of unclear etiology. An imbalance between von Willebrand factor (VWF) and ADAMTS-13 is an emerging variable in thrombosis. Objectives To describe perioperative changes to VWF, ADAMTS-13 and NETosis, and evaluate clinical and biochemical associations with postoperative thrombosis. Methods Neonates and infants undergoing palliation or definitive surgical repair of congenital heart malformations were recruited (n = 133). Preoperative and postoperative plasma levels of VWF, ADAMTS-13 and markers of NETosis were determined. Patients were followed for up to 30 days for the occurrence of thrombosis. Univariate and multivariate logistic regression analyses were conducted to identify variables associated with thrombosis. Results We identified significant postoperative increases in VWF activity, VWF level, DNA-histone complexes and cell-free DNA with an overall decrease in ADAMTS-13 activity. Patients experiencing postoperative thrombotic events (9%) were characterized by surgery performed at a lower intraoperative temperature, higher preoperative lactic acid levels, and higher preoperative VWF activity and level. A multivariate logistic regression model identified preoperative VWF activity (odds ratio (OR) 8.39 per IU mL-1 , 95% confidence interval [CI] 1.73-40.55) and transfusion of cryoprecipitate (OR 1.10 per mL kg-1 , 95% CI 1.03-1.17) as being associated with thrombosis. Conclusions Pediatric patients undergoing surgical repair of congenital heart malformations are exposed to high levels of VWF with diminished or minimal change to ADAMTS-13 in the immediate postoperative period. Elevated preoperative VWF activity is associated with postoperative thrombosis in pediatric congenital heart disease.


Polymorphonuclear-MDSCs Facilitate Tumor Regrowth After Radiation by Suppressing CD8+ T Cells.
Radiation therapy (RT) is widely used in the treatment of cancer. Unfortunately, RT alone is insufficient to control the disease in most cases, as regrowth after irradiation still occur. Thus, it would be meaningful to explore the underlying mechanism of tumor regrowth after irradiation. Myeloid-derived suppressor cells (MDSCs) contribute to the immunosuppressive tumor microenvironment and hinder the therapeutic efficacy of RT. However, it is unclear whether MDSCs-mediated immune suppression contributes to local relapse after irradiation. In this article, we tried to figure out how MDSCs sabotage the therapeutic effect of RT, and tried to determine the potential synergistic effect of combination between targeting MDSCs and RT. A syngeneic murine model of Lewis lung cancer was used. The abundance of tumor infiltrating MDSCs and tumor growth after irradiation was assessed. The percentage and functional state of CD8+ T cells were measured by flow cytometry, with or without polymorphonuclear (PMN)-MDSCs depletion. Arginase 1 (ARG1) expression and activity of MDSCs were examined by hematoxylin and eosin staining and flow cytometry. ARG1 inhibitor and phosphodiesterase 5 inhibitor sildenafil were administered after RT to figure out the underlying mechanism of MDSCs-mediated immunosuppression. We demonstrated that irradiation recruited MDSCs, especially the polymorphonuclear subset, into the tumor microenvironment. PMN-MDSCs inhibited the CD8+ T cell response by elevating ARG1 expression. Selective depletion of PMN-MDSCs or inhibition on ARG1 promoted the infiltration and activation of intratumoral CD8+ T cells, and delayed tumor regrowth after irradiation. We showed that sildenafil reduced the accumulation and ARG1 expression of PMN-MDSCs after irradiation, thus abrogating the MDSCs-mediated immunosuppression. Our results have suggested that PMN-MDSCs participate in the irradiation-induced immune suppression through ARG1 activation. We have also found that sildenafil has the potential to facilitate antitumor immunity, which provides a new alternative to delay tumor recurrence after RT.


Molecular characterization of a surface protein antigen gene from serotype c Streptococcus mutans, implicated in dental caries.
The complete nucleotide sequence of the gene for a cell-surface protein antigen (PAc) of Streptococcus mutans MT8148 (serotype c) was determined. The pac gene consisted of 4695 bp and coded for a 170773D protein. The pac gene product contained a putative 38 amino acid signal peptide, resulting in a 166817D mature protein. A potential promoter sequence and a putative Shine-Dalgarno sequence preceded the open reading frame. Two internal repeating amino acid sequences were present in the PAc. One repeating region located in the N-terminal region was rich in alanine, and the other located in the central region was rich in proline. Southern blot analysis under the less stringent condition (allowing up to 35% base mismatch) revealed that the probe covering the proline-rich region hybridized to DNA preparations from strains of Streptococcus cricetus, Streptococcus sobrinus and Streptococcus downei as well as Streptococcus mutans.


Expression, purification, and structural analysis of the full-length human integral membrane protein γ-sarcoglycan.
Mutation of the gene encoding γ-sarcoglycan (SGCG), an integral membrane protein responsible for maintaining the integrity of the muscle cell sarcolemma, results in Limb-Girdle Muscular Dystrophy (LGMD), a congenital disease with no current treatment options. This member of the sarcoglycan glycoprotein family is a vital component of the Dystrophin Complex, which together facilitate normal muscle function. However, very little is known about the structure and dynamics of these proteins, and of membrane glycoproteins in general. This is due to a number of factors, including their complexity, heterogeneity and highly-specific native environments. The expression, purification, and structural study of membrane proteins is further impeded by their hydrophobic nature and consequent propensity to aggregate in aqueous solutions. Here, we report the first successful expression and purification of milligram quantities of full-length recombinant SGCG, utilizing fusion protein-guided overexpression to inclusion bodies in Escherichia coli. Purification of SGCG from the fusion protein, TrpΔLE, was facilitated using chemical cleavage. Cleavage products were then isolated by size-exclusion chromatography. Successful purification of the protein was confirmed using SDS-PAGE and mass spectroscopy. Finally, solution nuclear magnetic resonance spectroscopy of uniformly 15N-labeled SGCG in detergent environments was performed, yielding the first spectra of the full-length membrane glycoprotein, SGCG. These results represent the initial structural studies of SGCG, laying the foundation for further investigation on the interaction and dynamics of other integral membrane proteins. More specifically, this data allows for opportunities in the future for enhanced treatment modalities and cures for LGMD.


A user-friendly web portal for analyzing conformational changes in structures of Mycobacterium tuberculosis.
Initiation of the Tuberculosis Structural Consortium has resulted in the expansion of the Mycobacterium tuberculosis (MTB) protein structural database. Currently, 969 experimentally solved structures are available for 354 MTB proteins. This includes multiple crystal structures for a given protein under different functional conditions, such as the presence of different ligands or mutations. In depth analysis of the multiple structures reveal that subtle differences exist in conformations of a given protein under varied conditions. Therefore, it is immensely important to understand the conformational differences between the multiple structures of a given protein in order to select the most suitable structure for molecular docking and structure-based drug designing. Here, we introduce a web portal ( http://bmi.icmr.org.in/mtbsd/torsion.php ) that we developed to provide comparative data on the ensemble of available structures of MTB proteins, such as Cα root means square deviation (RMSD), sequence identity, presence of mutations and torsion angles. Additionally, torsion angles were used to perform principal component analysis (PCA) to identify the conformational differences between the structures. Additionally, we present a few case studies to demonstrate this database. Graphical Abstract Conformational changes seen in the structures of the enoyl-ACP reductase protein encoded by the Mycobacterial gene inhA.


Spermatogonial stem cell transplantation and testicular function.
Spermatogonial stem cells (SSCs) are responsible for the continual production of spermatozoa throughout adult life. Interactions between SSCs and the surrounding cells in the seminiferous tubules regulate the biological activity of these cells. Factors involved in the regulation of SSCs are beginning to be defined by animal models and the culture of SSCs in defined media. A critical development in the characterization of SSCs has been the development of the germ cell transplantation technique, which provides the only assay for the presence of SSCs in a population of cells, and which allows the determination of whether SSCs are proliferating or differentiating in culture. This approach has accelerated SSC-focused research and promises to provide a better understanding of the factors and mechanisms that regulate these cells. The knowledge provided by this work is also critical to an appraisal of the components of the SSC niche in the seminiferous epithelium. Thus, many aspects of testicular function can be defined by the investigation of SSCs and the factors, cells, and environment that regulate SSCs, thereby leading to a more comprehensive understanding of spermatogenesis.


Diaminobenzidine reactions in control and treated Amoeba proteus.
Cytochrome oxidase activity was demonstrated in Amoeba proteus by diaminobenzidine (DAB) cytochemistry. Deposition of the reaction product occurred on the inner mitochondrial membranes and the cristae. The reaction was abolished by cyanide incubations. Positive reactions were produced with both unfixed and fixed cells: although staining potential was destroyed by any prefixatives which included glutaraldehyde. Cells prefixed with 4% formaldehyde, to raise structural preservation, retained staining ability. Amoebae subjected to prolonged anaerobiosis or to treatment with the carcinogen N-methyl-N-nitrosourethane (MNU) displayed a reduction in DAB reactivity. A positive reaction was only produced in incubations of unfixed cells and even in these the intensity of cristal staining was depleted. The possible use of DAB reactions where lesions in mitochondrial functioning have occurred is considered.


Once is enough for hippocampal replay.
In this issue of Neuron, Berners-Lee et al. (2022) reveal how neural dynamics in the hippocampus change after a single experience, offering a candidate mechanism for how hippocampal plasticity supports episodic memory.


Fibromuscular dysplasia of the carotid arteries complicating pregnancy.
Fibromuscular dysplasia is an arteriopathy of unknown etiology that affects the intermediate-size branches of the aorta. Partial occlusion of these arteries may result in neurologic symptoms when carotid arteries are affected, and impaired liver or kidney function when their blood supply is compromised. Pregnancy and delivery in women who are diagnosed as having fibromuscular dysplasia may be associated with disease-related complications such as ischemic attacks. We report the course of a pregnancy and delivery in a patient with carotid artery fibromuscular dysplasia and suggest steps for general obstetric management and contraception in patients suffering from fibromuscular dysplasia.


Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging.
The epidermal barrier is renewed by the activation, proliferation, and differentiation of keratinocyte stem cells after injury and aging impedes this repair process through undefined mechanisms. We previously identified a gene signature of metabolic dysfunction in aged murine epidermis, but the precise regulators of epidermal repair and age-related growth defects are not well established. Aged mouse models as well as mice with conditional epidermal loss of the metabolic regulator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were used to explore the cellular pathways which control skin repair after injury and stress. Aged mice or those with epidermal Pgc-1α deletion (epiPgc-1α KO) and young or Pgc1afl/fl controls were subjected to wound injury, UVB exposure or the inflammatory agent TPA. In vivo and ex vivo analyses of wound closure, skin structure, cell growth and stem cell differentiation were used to understand changes in epidermal re-growth and repair resulting from aging or Pgc-1α loss. Aging impairs epidermal re-growth during wound healing and results in lower expression of Pgc-1α. Mice with conditional deletion of epidermal Pgc-1α exhibit greater inflammation- and UVB-induced cell differentiation, reduced proliferation, and slower wound healing. epiPgc-1α KO mice also displayed reduced keratinocyte NAD+ levels, shorter telomeres, and greater poly ADP-ribosylation, resulting in enhanced stress-stimulated p53 and p21 signaling. When NAD+ was reduced by Pgc-1α loss or pharmacologic inhibition of NAD+ synthesis, there was reduced stress-induced proliferation, increased differentiation, and protection against DNA damage via enhanced epidermal shedding. Similarly, aged mice exhibit disrupted epidermal NAD+ homeostasis and enhanced p53 activation, resulting in p21 growth arrest after wounding. NAD+ precursor treatment restores epidermal growth from old skin to that of young. Our studies identify a novel role for epidermal Pgc-1α in controlling epidermal repair via its regulation of cellular NAD+ and downstream effects on p53-driven growth arrest. We also establish that parallel mechanisms are evident in aged epidermis, showing that NAD+ signaling is an important controller of physiologic skin repair and that dysfunction of this pathway contributes to age-related wound repair defects.


The influence of the mycotoxin deoxynivalenol on jejunal glucose transport in pigs.
The experiments were aimed at evaluating whether the activity of the glucose transporter in the pig's jejunum is affected by deoxynivalenol (DON)-contaminated feed. This is based on the ability of DON to inhibit the protein synthesis on cellular level which might also involve the synthesis of the intestinal glucose transporter.Two groups of six castrated male pigs were restrictively fed a control or a DON contaminated diet (=5.7 mg/kg). Immediately after slaughtering the pigs, the mid-jejunum was quickly dissected, washed, frozen and stored at -80°C until preparations. Brush border membrane vesicles (BBMV) were prepared by Mg(2+)-EGTA-precipitation and differential centrifugation. The activity of the glucose transporter was examined by measuring the uptake of [(3)H]-glucose into the BBMV. The glucose uptake was quantified by using the rapid filtration technique.The glucose uptake into BBMV followed Michaelis-Menten-kinetic. Comparison of the kinetic parameters Vmax (transport capacity) and Km (transport affinity) of the two treatment-groups showed no significant differences between feeding a DON-contaminated or control diet. It was concluded that dietary DON exposure (=5.7 mg/kg) for five weeks had no obvious influence on the intestinal glucose transporter and its activity in pigs.


Erratum to "A new accelerometer (Fibion) device provides valid sedentary and upright time measurements compared to the ActivPAL4 in healthy individuals" [Heliyon 8(10) (October 2022) e1103].
[This corrects the article DOI: 10.1016/j.heliyon.2022.e11103.].


Forced synthesis of trace amounts of juvenile hormone II from propionate by corpora allata of a juvenile hormone III-producing insect.
Corpora allata of the cockroach Diploptera punctata normally synthesize only the isoprenoid juvenile hormone III (JH III). Only under extreme in vitro conditions (absence of carbon sources other than propionate) do they produce trace amounts of the homoisoprenoid JH II in addition to JH III. The specificity of the in vitro synthesis of JH III by D. punctata is thus consistent with the observed lack of homoisoprenoid JHs in this insect.


Epidoxorubicin plus ifosfamide in advanced and/or metastatic soft-tissue sarcomas.
We undertook this phase II study to evaluate the efficacy and toxicity of epidoxorubicin and ifosfamide in the treatment of locally advanced and/or metastatic soft-tissue sarcomas. We used escalating doses of epidoxorubicin (from 60 to 75 mg/m2) on day 1 and 1.2 g/m2 ifosfamide on days 1-5. Chemotherapy courses were repeated every 3-4 weeks. A total of 16 patients--13 who had not previously been treated and 3 who had undergone prior therapy with anthracyclines--entered the study. In all, 15 patients were evaluable for response and 16, for toxicity. At least two courses of chemotherapy were given. A complete remission (CR) was seen in 1 patient, a partial remission (PR) in 5, and a minor response (MR) in 1, for an objective response rate (CR + PR) of 40% (6/15); this value reached 50% in non-pretreated patients (6/12). Stable disease (SD) was observed in 40% (6/15) of patients. The relative dose intensity of epidoxorubicin ranged from 10 to 23.3 mg/m2 (median, 16.6 mg/m2). The time to objective response ranged from 4 to 12 weeks (median, 8.5 weeks). The duration of response was 4 months for the single CR, and that for the five PRs was 6+ months (range, 4-18 months). Toxicity was evaluated according to WHO criteria in 16 patients; it was mild and consisted mainly of alopecia, nausea and vomiting, and leucopenia. In only three patients did we observe grade 3 leucopenia. In one case an ifosfamide-associated encephalopathy occurred, but it regressed after 24 h. Neither chronic nor acute cardiac toxicity was reported. In this preliminary analysis, the response rate obtained with the combination of epidoxorubicin and ifosfamide was encouraging and the toxicity was acceptable.


Peripheral nerve injuries in the pediatric population: a review of the literature. Part III: peripheral nerve tumors in children.
Peripheral nerve tumors type, inciedence and treatment in the pediatric population should be analyzed. We have performed an extense literature review of this subject. incidence and distribution are similar to those observed in adults. The most common peripheral nerve tumors in children are neurofibromas and schwannomas. Malignant peripheral nerve sheath tumors are also observed, specially associated with genetic syndromes, like neurofibromatosis and Carney complex. In this review, peripheral nerve tumors have been divided into three categories to aid with understanding: reactive and hyperplastic lesions, benign tumors, and malignant tumors. The most frequent lesions have been described.


A neural model of the frontal eye fields with reward-based learning.
Decision-making is a flexible process dependent on the accumulation of various kinds of information; however, the corresponding neural mechanisms are far from clear. We extended a layered model of the frontal eye field to a learning-based model, using computational simulations to explain the cognitive process of choice tasks. The core of this extended model has three aspects: direction-preferred populations that cluster together the neurons with the same orientation preference, rule modules that control different rule-dependent activities, and reward-based synaptic plasticity that modulates connections to flexibly change the decision according to task demands. After repeated attempts in a number of trials, the network successfully simulated three decision choice tasks: an anti-saccade task, a no-go task, and an associative task. We found that synaptic plasticity could modulate the competition of choices by suppressing erroneous choices while enhancing the correct (rewarding) choice. In addition, the trained model captured some properties exhibited in animal and human experiments, such as the latency of the reaction time distribution of anti-saccades, the stop signal mechanism for canceling a reflexive saccade, and the variation of latency to half-max selectivity. Furthermore, the trained model was capable of reproducing the re-learning procedures when switching tasks and reversing the cue-saccade association.


Design Implementation and Evaluation of a Mobile Continuous Blood Oxygen Saturation Monitoring System.
In this study, we built a mobile continuous Blood Oxygen Saturation (SpO2) monitor, and for the first time, explored key design principles towards daily applications. We firstly built a customized wearable computer that can sense two-channel photoplethysmogram (PPG) signals, and transmit the signals wirelessly to smartphone. Afterwards, we explored many SpO2 model building principles, focusing on linear/nonlinear models, different PPG parameter calculation methods, and different finger types. Moreover, we further compared PPG sensor placement principles by comparing different hand configurations and different finger configurations. Finally, a dataset collected from eleven human subjects was used to evaluate the mobile health monitor and explore all of the above design principles. The experimental results show that the root mean square error of the SpO2 estimation is only 1.8, indicating the effectiveness of the system. These results indicate the effectiveness of the customized mobile SpO2 monitor and the selected design principles. This research is expected to facilitate the continuous SpO2 monitoring of patients with clinical indications.


The ultrasonographic diagnosis of typhlitis (neutropenic colitis).
Typhlitis is a necrotizing inflammatory disease of the cecum, usually with secondary infection. It is most often found in acute leukemia patients on chemotherapy but has also been reported in other patients on chemotherapeutic drugs. Diagnostic features of typhlitis have been reported on plain radiographs, barium enema, angiography, CT, and one other reported case with ultrasound. We report three cases of typhlitis with a characteristic echogenic thickening of the mucosa on ultrasound. The sonographic findings in the one previous report were identical to those of our three cases. We believe that the sonographic findings of typhlitis are unique and that ultrasound offers an easy noninvasive method of diagnosing this potentially lethal disease.


Nanoscale arrays of antimony telluride single crystals by selective chemical vapor deposition.
Arrays of individual single nanocrystals of Sb2Te3 have been formed using selective chemical vapor deposition (CVD) from a single source precursor. Crystals are self-assembled reproducibly in confined spaces of 100 nm diameter with pitch down to 500 nm. The distribution of crystallite sizes across the arrays is very narrow (standard deviation of 15%) and is affected by both the hole diameter and the array pitch. The preferred growth of the crystals in the <1 1 0> orientation along the diagonal of the square holes strongly indicates that the diffusion of adatoms results in a near thermodynamic equilibrium growth mechanism of the nuclei. A clear relationship between electrical resistivity and selectivity is established across a range of metal selenides and tellurides, showing that conductive materials result in more selective growth and suggesting that electron donation is of critical importance for selective deposition.


Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head.
Survival of patients with adenocarcinoma of the pancreas (PDAC) is poor and has remained almost unchanged over the past decades. The genomic landscape of PDAC has been characterized in recent years. The aim of this study was to identify a genetic profile as a possible predictor of prolonged survival in order to tailor therapy for PDAC patients. Panel next generation sequencing (NGS) and immunohistochemistry (IHC) were performed on paraffin-embedded tumor tissues from curatively treated PDAC patients. Tumor slides were re-evaluated with a focus on the histomorphology. Patients were subgrouped according to short and long overall (<4 years/>4 years) and disease-free (<2 years/>2 years) survival. Thirty-nine patients were included in the study. Clinicopathological staging variables as well as the histomorphological subgroups were homogenously distributed between short- and long-term overall and disease-free survivors. In survival analysis, patients with the KRAS G12D mutation and patients with TP53 nonsense and splice-site mutations had a significantly worse overall survival (OS) and disease-free survival (DFS). Patients with long-term OS and DFS showed no KRAS G12D, no TP53 nonsense or splice-site mutations. Rare Q61H/D57N KRAS mutations were only found in long-term survivors. The allele frequency rate of KRAS and TP53 mutations in tumor cells was significantly higher in short-term disease-free survivors and overall survivors, respectively. NGS of PDAC revealed significant differences in survival outcome in a patient collective with homogenously distributed clinicopathological variables. Further multi-institutional studies are warranted to identify more long-term survivors to detect genetic differences suitable for targeted therapy.


Nanoconfinement effects on hydrated excess protons in layered materials.
Thin water layers confined between surfaces are known for their surprising properties. Layered minerals, such as mackinawite, are naturally occurring systems where water is known to intercalate. Here we report, based on ab initio simulations, how excess protons can be hosted by the resulting nanostructured water film depending on the mackinawite interlayer distance. Even extreme nanoconfinement due to the mackinawite sheets is shown to not affect the dynamical nature of the topological defect, thus not localizing the excess protons but rather conserving the efficient structural (Grotthuss) diffusion process known in bulk water. Yet, depending on the width of the slit pore, the defect can bridge the bilayer water structure, thus forcing the excess proton into the water-depleted region between the bilayers.


A Prospective Multicenter Study of Leukopenia in Infants Younger Than Ninety Days With Fever Without Source.
Little is known about the value of leukopenia for assessing the risk of having a bacterial infection in young febrile infants. Infants younger than 90 days with fever without source were prospectively recruited between October 2011 and September 2013 in 19 Spanish Pediatric Emergency Departments. We analyzed the prevalence of invasive bacterial infection (IBI, positive blood or cerebrospinal fluid culture) and non-IBI (urinary tract infections and any other microbiologically confirmed bacterial infection excluding IBIs) by leukocyte count and general appearance. Among the 3401 infants recruited, 680 were diagnosed with non-IBIs (19.9%) and 107 with IBIs (3.1%). Overall, 244 infants had leukopenia (<5000 cells/mcL), 2369 a normal leukocyte count and 790 leukocytosis (>15,000 cells/mcL). Among the 3034 well-appearing patients, those with leukopenia had a lower prevalence of non-IBI [8.1% vs. 14.7%; odds ratio (OR) 0.51 (95% confidence interval (CI): 0.29-0.88)] and a similar prevalence of IBI [2.5% vs. 2.0%; OR, 1.20 (95% CI: 0.44-3.44)] compared with those with a normal leukocyte count. Among the 367 not-well-appearing infants, those with leukopenia had a similar prevalence of non-IBI [8.9% vs. 14.7%; OR, 0.57 (95% CI: 0.16-1.79)] and a higher prevalence of IBI [17.8% vs. 6.9%; OR, 2.90 (95% CI: 1.06-7.78)]. In the subgroup of well-appearing infants 22-90 days old without leukocyturia according to urine dipstick results, prevalence of both non-IBIs and IBIs was similar in patients with leukopenia and those with a normal leukocyte count. Leukopenia in well-appearing young febrile infants should not be considered a risk factor for having a bacterial infection.


Histopathological effects in tissues of snail Lymnaea stagnalis (Gastropoda, Pulmonata) exposed to sublethal concentration of Thiodan and recovery after exposure.
Histopathological alterations induced by Thiodan in three tissues, namely, digestive gland, foot and mantle, of the freshwater snail Lymnaea stagnalis were investigated. Specimens of Lymnaea stagnalis were exposed to 0.36% and 0.72% Thiodan 35 EC, a commercial grade of endosulfan, for 96 h followed by a recovery period of 30 days. Thiodan caused significant dose dependent histopathological changes in all the tissues of the snail. Irreversible necrotic changes occurred in the digestive gland of the snail following Thiodan exposure. Degenerative changes in the muscle fiber of the foot, protein and pigment cells of the foot and the connective tissue element of the mantle were recovered after 30 days of recovery of the snail in pesticide-free freshwater.


Performance of colorimetric reverse transcription loop-mediated isothermal amplification as a diagnostic tool for SARS-CoV-2 infection during the fourth wave of COVID-19 in Thailand.
COVID-19, which is caused by SARS-CoV-2 and its variants, poses an ongoing global threat, particularly in low-immunization coverage regions. Thus, rapid, accurate, and easy-to-perform diagnostic methods are in urgent demand to halt the spread of the virus. We aimed to validate the clinical performance of the FastProof 30 min-TTR SARS-CoV-2 reverse transcription loop-mediated isothermal amplification (RT-LAMP) method using leftover RNA samples extracted from 315 nasopharyngeal swabs. The sensitivity and specificity of RT-LAMP were determined in comparison with reverse transcriptase-polymerase chain reaction (RT-PCR). Of 315 nasopharyngeal swabs, viral RNA was detected in 154 samples (48.9%) by RT-PCR assay. Compared with RT-PCR, overall sensitivity and specificity of RT-LAMP were 81.82% (95% CI: 74.81-87.57) and 100% (95% CI: 97.73-100), respectively. A 100% positivity rate was achieved in samples with cycle threshold (Ct) <31 for RT-PCR targeting the ORF1ab gene. However, samples with Ct >31 accounted for false-negative results by RT-LAMP in 28 samples. RT-LAMP reliably detected viral RNA with high sensitivity and specificity and has potential application for mass screening of patients with acute COVID-19 infection when viral load is high.


Weekend Effect on in-Hospital Mortality for Ischemic and Hemorrhagic Stroke in US Rural and Urban Hospitals.
Previous studies have reported a "weekend effect" on stroke mortality, whereby stroke patients admitted during weekends have a higher risk of in-hospital death than those admitted during weekdays. We aimed to investigate whether patients with different types of stroke admitted during weekends have a higher risk of in-hospital mortality in rural and urban hospitals in the US. We used data from the 2016 National Inpatient Sample and used logistic regression to assess in-hospital mortality for weekday and weekend admissions among stroke patients aged 18 and older by stroke type (ischemic or hemorrhagic) and rural or urban status. Crude stroke mortality was higher in weekend admissions (p <0.001). After adjusting for confounding variables, in-hospital mortality among hemorrhagic stroke patients was significantly greater (22.0%) for weekend admissions compared to weekday admissions (20.2%, p = 0.009). Among rural hospitals, the in-hospital mortality among hemorrhagic stroke patients was also greater among weekend admissions (36.9%) compared to weekday admissions (25.7%, p = 0.040). Among urban hospitals, the mortality of hemorrhagic stroke patients was 21.1% for weekend and 19.6% for weekday admissions (p = 0.026). No weekend effect was found among ischemic stroke patients admitted to rural or urban hospitals. Our results help to understand mortality differences in hemorrhagic stroke for weekend vs. weekday admissions in urban and rural hospitals. Factors such as density of care providers, stroke centers, and patient level risky behaviors associated with the weekend effect on hemorrhagic stroke mortality need further investigation to improve stroke care services and reduce weekend effect on hemorrhagic stroke mortality.


The effects of midwives' job satisfaction on burnout, intention to quit and turnover: a longitudinal study in Senegal.
Despite working in a challenging environment plagued by persistent personnel shortages, public sector midwives in Senegal play a key role in tackling maternal mortality. A better understanding of how they are experiencing their work and how it is affecting them is needed in order to better address their needs and incite them to remain in their posts. This study aims to explore their job satisfaction and its effects on their burnout, intention to quit and professional mobility. A cohort of 226 midwives from 22 hospitals across Senegal participated in this longitudinal study. Their job satisfaction was measured from December 2007 to February 2008 using a multifaceted instrument developed in West Africa. Three expected effects were measured two years later: burnout, intention to quit and turnover. Descriptive statistics were reported for the midwives who stayed and left their posts during the study period. A series of multiple regressions investigated the correlations between the nine facets of job satisfaction and each effect variable, while controlling for individual and institutional characteristics. Despite nearly two thirds (58.9%) of midwives reporting the intention to quit within a year (mainly to pursue new professional training), only 9% annual turnover was found in the study (41/226 over 2 years). Departures were largely voluntary (92%) and entirely domestic. Overall the midwives reported themselves moderately satisfied; least contented with their "remuneration" and "work environment" and most satisfied with the "morale" and "job security" facets of their work. On the three dimensions of the Maslach Burnout Inventory, very high levels of emotional exhaustion (80.0%) and depersonalization (57.8%) were reported, while levels of diminished personal accomplishment were low (12.4%). Burnout was identified in more than half of the sample (55%). Experiencing emotional exhaustion was inversely associated with "remuneration" and "task" satisfaction, actively job searching was associated with being dissatisfied with job "security" and voluntary quitting was associated with dissatisfaction with "continuing education". This study found that although midwives seem to be experiencing burnout and unhappiness with their working conditions, they retain a strong sense of confidence and accomplishment in their work. It also suggests that strategies to retain them in their positions and in the profession should emphasize continuing education.


Excited-state double-proton transfer in the 7-azaindole dimer in the gas phase. 3. Reaction mechanism studied by picosecond time-resolved REMPI spectroscopy.
The excited-state double-proton-transfer (ESDPT) reaction in the jet-cooled 7-azaindole dimer (7AI2) has been investigated with picosecond time-resolved resonance-enhanced multiphoton ionization spectroscopy. The observed decay profiles of 7AI2 by exciting the origin and the intermolecular stretch fundamental in the S1 state are well reproduced by single-exponential functions with time constants of 1.9 +/- 0.9 ps and 860 +/- 300 fs, respectively. This result provides clear evidence of the concerted mechanism of ESDPT in 7AI2.


Primary intestinal T-cell lymphoma and sclerosing cholangitis: a cytokine-mediated association?
A 63-year-old woman with a 1-year history of abdominal pain and intrahepatic cholestasis developed anorexia, weight loss, lassitude and diarrhoea. Studies led to a diagnosis of primary intestinal T-cell lymphoma involving especially the proximal small intestine and infiltrating the mesenteric lymph nodes, bone marrow and skin. An associated severe hypoalbuminaemia (1.3 g dL-1) was most probably the result of protein-losing enteropathy. Liver biopsy demonstrated concentric fibrosis of the bile ducts ('onion skin' lesions, with an inflammatory cell infiltrate and lymphoid aggregates) and was considered almost pathognomonic of primary sclerosing cholangitis. Sudden death due to pulmonary embolism occurred and a limited autopsy confirmed the diagnosis. Other associated diseases such as coeliac disease or inflammatory bowel disease were not found. This first report of the simultaneous occurrence of two rare diseases - primary sclerosing cholangitis and intestinal T-cell lymphoma - may indicate an intriguing association, possibly mediated by the effect of cytokines released by the infiltrating T-cells into the portal circulation.


Technique for insertion of apicoaortic conduit.
A technique for insertion of an apicoaortic prosthesis is described. It provides a hemostatic aortic and ventricular anastomosis and can be performed with a minimum of bypass time and without interruption of coronary circulation. The technique requires no special instruments.


Assessment of bone quality using buccal and palatal autogenous cortical shells harvested from two different mandibular donor sites for maxillary alveolar ridge augmentation: a histomorphometric randomized clinical trial.
This study aims to compare the quality of free autogenous bone grafts harvested from two different mandibular donor sites, used as onlay shells to augment horizontally and vertically deficient anterior maxillary alveolar ridges. Fourteen patients with edentulous and atrophic anterior maxillae are randomly allocated into two groups. Seven symphyseal chin (group I) and seven retromolar (group II) mandibular bone grafts were harvested and fashioned to construct buccal and palatal frameworks, fixed in place with mini-screws, followed by compacting the inter-positional gaps with an equal particulate mix of xenograft and autogenous cancellous particulates. Six months later, 42 core biopsies, three from each patient, 21 for each study group, were retrieved before the implants' insertion and subjected to histomorphometric bone area percent analysis. The bone area percent of the newly formed bone augmented with the chin shells was 52.53 ± 1.68% versus 47.97 ± 1.83% for the retromolar grafts. The mean area percent difference between both groups was statistically significant (p = 0.0004). A higher bone quality and more volumetric stability were associated with the symphyseal cortical shells. The study was registered on www.clinicaltrials.gov (#: NCT03607006) in July 2018 by Ola Alaa El Morsy.


Improving stroke clinical guideline adherence in an Australian hospital using a clinician-led implementation process.
Private hospitals in Australia manage 11% of acute and 48% of rehabilitation stroke admissions, yet little is known about implementation of stroke clinical guidelines in this setting. Clinical guidelines recommend that acute stroke patients be co-located in a stroke unit in a geographically defined area, rather than dispersed across the hospital. To investigate post-intervention adherence to clinical guidelines for stroke management, and to explore staff barriers and facilitators to guideline implementation. Observational study before-and-after local implementation of Australian stroke clinical guidelines. The primary outcome was a change in the proportion of patients who were physically co-located in an acute stroke unit. Secondary outcomes included changes in adherence to additional acute and rehabilitation guideline criteria, and staff identification of barriers and facilitators to guide implementation. Data were collected from medical record audits, health service information and staff surveys. Co-location in an acute stroke unit did not change significantly after guideline implementation (49% adherence pre-intervention and 54% post-intervention). Across acute and rehabilitation wards, 15% (11/72) of guideline criteria improved (p < .05). These related to assessments of swallowing and neglect, presence of a stroke care co-ordinator and occupational therapist, post-discharge care plan, provision of patient education and return to driving. Facilitators to guideline implementation included staff education, collaboration, and dissemination of user-friendly stroke policies. Stroke clinical guideline implementation led to a favorable uptake of some criteria, yet not all. Implementation was assisted by staff education, user-friendly stroke policies and multidisciplinary team collaboration. ANZCTR: registration number ACTRN12616000646448 (http://www.ANZCTR.org.au/ACTRN12616000646448.aspx).


Continuous-wave infrared subsurface optical stimulation of the rat prostate cavernous nerves using a 1490-nm diode laser.
To optimize the infrared laser wavelength and optical nerve stimulation (ONS) parameters for both deep and rapid subsurface cavernous nerve (CN) stimulation in a rat model, in vivo. A 150-mW, 1490-nm diode laser providing an optical penetration depth (OPD) of 518 μm in water was operated in continuous-wave mode during stimulation of the CNs in 8 rats for 15 seconds irradiation time through a custom-built, single-mode fiber optic probe capable of producing a collimated, 1-mm diameter laser beam. Successful ONS was judged by an intracavernous pressure response in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 nm and 1550 nm near-infrared diode laser wavelengths. Subsurface ONS of the rat CN was successful through fascia layers with a thickness up to 380 μm using an incident laser power of ∼50 mW. Intracavernous pressure response times as short as 4.6 ± 0.2 seconds were recorded using higher laser powers below the nerve damage threshold. The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper penetration than 1455-nm diode laser and more rapid and efficient nerve stimulation than 1550-nm diode laser.


Prognostic significance of anemia in patients with chronic systolic heart failure secondary to Chagas' cardiomyopathy.
The purpose of this study was to evaluate the prognostic significance of anemia on outcome of patients with chronic systolic heart failure secondary to Chagas' cardiomyopathy, as no previous study has previously addressed this question. One-hundred-eight-six patients followed for chronic systolic heart failure secondary to Chagas' cardiomyopathy at our Institution from January 2000 to December 2008 were studied. Forty-nine (26%) patients were found to have anemia; 37 (20%) were men and 12 (6%) were women. Mean hemoglobin level was 14.1±1.2g/L in patients with no anemia and 11.5±1.2g/L in patients with anemia. On a Cox proportional hazards multivariate analysis, anemia was a predictor of all-cause mortality neither in the univariate nor in the multivariate analysis. Mean serum sodium (Hazard ratio=0.92; Beta-coefficient=-0.09; 95% confidence interval 0.89-0.96; p value<0.005), and Beta-Blocker therapy (Hazard ratio=0.40; 95% confidence interval 0.26-0.61; p value<0.005) were retained as independent predictors of mortality for patients with Chagas' cardiomyopathy with chronic heart failure. Probability of survival for patients with anemia, however, was significantly lower in patients with anemia in comparison to patients with no anemia, mainly in patients with advanced heart failure. Anemia is not an independent predictor of all-cause mortality in patients with Chagas' cardiomyopathy with chronic systolic heart failure. Probability of survival is poorer in patients with anemia than in those without.


Analysis of biological rhythms using an interactive structured autoregressive modelling technique.
A method of spectral-type analysis for rhythmic biomedical data is presented based on autoregressive modelling techniques. The emphasis has been on portability between data-processing machines, so that the programmes are written in FORTRAN 4 for the ICL 1900 series computers. The programmes are structured in blocks allowing for simple alteration to an interactive mode allowing the calculation and display of pre-filtering stages, model coefficients, the pole-zero plot, residuals, AR frequency spectrum, FFT of raw and filtered data. The method works on a small number of cycles and gives a direct read out of significant spectral components.


Rapid and inexpensive real-time PCR for genotyping functional polymorphisms within the Toll-like receptor -2, -4, and -9 genes.
The discovery of the human Toll-like receptors (TLRs) and the recognition of their pivotal role in sensing microbial pathogens during the last 5 years have resulted in a renewed appreciation of innate immunity. Due to their central role in both, triggering innate immunity as well as linking innate and adaptive immunity, genetic variations within the TLR genes, known to be associated with a variety of infectious diseases, are currently of great interest. Several single nucleotide polymorphisms (SNPs) within TLR genes have been described and seem to be associated with susceptibility to inflammatory diseases. However, methods for genotyping SNPs within the TLR genes, e.g. direct sequencing or polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis, are time-consuming. In this work, we report novel real-time PCR methods for genotyping five TLR SNPs within TLR-2, TLR-4 and TLR-9 that have been associated with various diseases using fluorescence labeled hybridization probes and the LightCycler instrument. In addition, we provide protocols employing a standard Taq polymerase in order to reduce substantially the costs for real-time PCR.