Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI.
Accurately characterising the brain networks involved in seizure activity may have important implications for our understanding of epilepsy. Intracranial EEG-fMRI can be used to capture focal epileptic events in humans with exquisite electrophysiological sensitivity and allows for identification of brain structures involved in this phenomenon over the entire brain. We investigated ictal BOLD networks using the simultaneous intracranial EEG-fMRI (icEEG-fMRI) in a 30 year-old male undergoing invasive presurgical evaluation with bilateral depth electrode implantations in amygdalae and hippocampi for refractory temporal lobe epilepsy. One spontaneous focal electrographic seizure was recorded. The aims of the data analysis were firstly to map BOLD changes related to the ictal activity identified on icEEG and secondly to compare different fMRI modelling approaches. Visual inspection of the icEEG showed an onset dominated by beta activity involving the right amygdala and hippocampus lasting 6.4 s (ictal onset phase), followed by gamma activity bilaterally lasting 14.8 s (late ictal phase). The fMRI data was analysed using SPM8 using two modelling approaches: firstly, purely based on the visually identified phases of the seizure and secondly, based on EEG spectral dynamics quantification. For the visual approach the two ictal phases were modelled as 'ON' blocks convolved with the haemodynamic response function; in addition the BOLD changes during the 30 s preceding the onset were modelled using a flexible basis set. For the quantitative fMRI modelling approach two models were evaluated: one consisting of the variations in beta and gamma bands power, thereby adding a quantitative element to the visually-derived models, and another based on principal components analysis of the entire spectrogram in attempt to reduce the bias associated with the visual appreciation of the icEEG. BOLD changes related to the visually defined ictal onset phase were revealed in the medial and lateral right temporal lobe. For the late ictal phase, the BOLD changes were remote from the SOZ and in deep brain areas (precuneus, posterior cingulate and others). The two quantitative models revealed BOLD changes involving the right hippocampus, amygdala and fusiform gyrus and in remote deep brain structures and the default mode network-related areas. In conclusion, icEEG-fMRI allowed us to reveal BOLD changes within and beyond the SOZ linked to very localised ictal fluctuations in beta and gamma activity measured in the amygdala and hippocampus. Furthermore, the BOLD changes within the SOZ structures were better captured by the quantitative models, highlighting the interest in considering seizure-related EEG fluctuations across the entire spectrum.


Highly Efficient Adsorption of Sr2+ and Co2+ Ions by Ambient Prepared Alkali Activated Metakaolin.
This study aimed to explore a low cost and sustainable adsorbent to remove Sr2+ and Co2+ ions, which are major radioactive ions in nuclear wastewater. The material properties of the alkali-activated metakaoline as a function of soaking time at ambient temperature from 1 day to 7 days were examined by XRD, XRF, SEM, and solid-state NMR. Adsorption isotherms were used to evaluate the appropriate soaking time for the optimal sorption performance for both Sr2+ and Co2+ ions. The alkali-activated metakaolin soaked for 3 days (BK3) presented the maximum adsorption capacities of 3.81 meq/g (167.5 mg/g) and 4.02 meq/g (118.5 mg/g) for Sr2+ and Co2+, respectively. The sorption mechanisms for Sr2+ and Co2+ in the BK3 sample were investigated, and the experimental results indicated that adsorption for Sr2+ was achieved via ion exchange. By contrast, surface complexation in combination with ion exchange contributed to the sorption mechanisms for the removal of Co2+. Competitive adsorption experiments revealed that the alkali-activated metakaolin favored the adsorption for divalent ions (i.e., Sr2+ and Co2+), and it was less effective for Cs+. Finally, the used adsorbent could be directly mineralized and vitrified by heat treatment to immobilize the Sr2+ and Co2+ ions.


An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation.
T cell immunoglobulin domain and mucin domain 3 (TIM3) was initially identified as an inhibitory molecule on IFNγ-producing T cells. Further research discovered the broad expression of TIM3 on different immune cells binding to multiple ligands. Apart from its suppressive effects on the Th1 cells, recent compelling experiments highlighted the indispensable role of TIM3 in the myeloid cell-mediated inflammatory response, supporting that TIM3 exerts pleiotropic effects on both adaptive and innate immune cells in a context-dependent manner. A large number of studies have been conducted on TIM3 biology in the disease settings of infection, cancer, and autoimmunity. However, there is a lack of clinical evidence to closely evaluate the role of T cell-expressing TIM3 in the pathogenesis of chronic kidney disease (CKD). Here, we reported an intriguing case of Mycobacterium tuberculosis (Mtb) infection that was characterized by persistent overexpression of TIM3 on circulating T cells and ongoing kidney tubulointerstitial inflammation for a period of 12 months. In this case, multiple histopathological biopsies revealed a massive accumulation of recruited T cells and macrophages in the enlarged kidney and liver. After standard anti-Mtb treatment, repeated renal biopsy identified a dramatic remission of the infiltrated immune cells in the tubulointerstitial compartment. This is the first clinical report to reveal a time-course expression of TIM3 on the T cells, which is pathologically associated with the progression of severe kidney inflammation in a non-autoimmunity setting. Based on this case, we summarize the recent findings on TIM3 biology and propose a novel model of CKD progression due to the aberrant crosstalk among immune cells.


Revisiting the Reduction of Stochastic Models of Genetic Feedback Loops with Fast Promoter Switching.
Propensity functions of the Hill type are commonly used to model transcriptional regulation in stochastic models of gene expression. This leads to an effective reduced master equation for the mRNA and protein dynamics only. Based on deterministic considerations, it is often stated or tacitly assumed that such models are valid in the limit of rapid promoter switching. Here, starting from the chemical master equation describing promoter-protein interactions, mRNA transcription, protein translation, and decay, we prove that in the limit of fast promoter switching, the distribution of protein numbers is different than that given by standard stochastic models with Hill-type propensities. We show the differences are pronounced whenever the protein-DNA binding rate is much larger than the unbinding rate, a special case of fast promoter switching. Furthermore, we show using both theory and simulations that use of the standard stochastic models leads to drastically incorrect predictions for the switching properties of positive feedback loops and that these differences decrease with increasing mean protein burst size. Our results confirm that commonly used stochastic models of gene regulatory networks are only accurate in a subset of the parameter space consistent with rapid promoter switching.


Heterogeneity of lipopolysaccharides from Yersinia pseudotuberculosis: chemical characterization of various molecular types.
Prior studies have shown some unusual changes in the lipopolysaccharides (LPSs) from Yersinia pseudotuberculosis that occur when the microbe is grown at low temperature; the specific features of these LPSs in comparison with the LPSs from other enteropathogens may be due to unusual thermal adaptation mechanisms. To gain insight into this question, the chemical composition of Y. pseudotuberculosis LPS has been determined. The data indicate that two different S-form LPS species are produced in "cold"-grown bacteria. These have an identical set of bands after SDS-PAGE, similar elution profiles during gel-filtration on a Sephadex G-200 column in the presence of sodium deoxycholate, identical monosaccharide and fatty acid compositions, and similar polymerization degrees, but they have different acylation degree. On the whole, the macromolecularly different LPS populations, varying not only in their smooth or rough nature and hydrophobicity, but also in their localization in the outer membrane and, probably, their interactions with other cell components, are synthesized in "cold"-grown Y. pseudotuberculosis. The biological sense of the heterogeneity and its connection with psychrophilic and pathogenic properties of pseudotuberculosis organisms are discussed.


Analysis of prognosis and treatment decisions for patients with second primary lung cancer following esophageal cancer.
As the long-term prognosis of esophageal cancer (EC) is improving, concerns of a second primary malignancy (SPM) have increased. However, research on lung cancer as the SPM after EC is limited. Therefore, we aimed to explore the prognostic factors and clinical treatment decisions of patients with second primary lung cancer following esophageal cancer (SPLC-EC). We identified the data of 715 patients with SPLC-EC from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2016. We established a nomogram through Cox regression modelling to predict the prognosis of patients with SPLC-EC. We determined the association between factors and cancer-specific mortality using the Fine-Gray competing risk model. Then, we performed survival analysis to evaluate the benefits of different treatment methods for overall survival (OS). The multivariate analysis indicated that sex, insurance recode, age, surgery and chemotherapy 0for first primary malignancy (FPM), primary site, stage, and surgery for SPM were independent prognostic factors for OS. Using concordance indices for OS, the nomogram of our cohort showed a higher value than the SEER historic-stage nomogram (0.8805 versus 0.7370). The Fine-Gray competing risk model indicated that surgery for FPM and SPM was the independent prognostic factor for EC-specific mortality (P=0.016, hazard ratio [HR] = 0.532) and LC-specific mortality (p=0.016, HR=0.457), respectively (p<0.001). Compared to the patient group having distant metastasis, patients with localized and regional metastasis benefitted from undergoing surgery for SPM (P<0.001, P<0.001, respectively). For patients without surgery for SPM, radiotherapy (P<0.001) and chemotherapy (P<0.001) could improve OS. Surgery remains the mainstay for managing SPLC-EC, especially for localized and regional tumors. However, chemotherapy and radiotherapy are recommended for patients who cannot undergo surgery. These findings can have implications in the treatment decision-making for patients with SPLC-EC.


Macular hole after phakic intraocular lens implantation: two cases with divergent manifestations.
Abstract We describe two cases of a macular hole (MH) which had divergent manifestations and clinical courses following implantation of an Implantable Collamer Lens (ICL) in two high myopic patients. The onset of symptoms and shape of the holes, which were observed by optical coherence tomography and fundoscopy, and prognosis of the visual acuity after the surgery of each patient, were quite different. In the first patient, the symptom was an acute onset. Fundoscopy showed a cuneiform-shaped hole with internal limiting membrane defect around the hole. The prognosis after the surgery was very poor, and the best corrected visual acuity was 0.08 after complete anatomical closure. In another patient, the MH showed insidious progression with disease-free interval from ICL implantation to MH onset. After the surgery, the best corrected visual acuity was recovered to 1.0.


Viability and efficacy of coverage of cryopreserved human skin allografts in mice.
Human skin allografts are considered one of the best temporary biological coverages for severe burn patients. Human skin allografts can be either viable or nonviable depending on their preservation modalities. However, there is a debate about the use of viable versus nonviable skin for severe burn patients because there is no established correlation between viability and efficacy of coverage. The authors tried to correlate the viability of cryopreserved human skin allografts as assessed by the MTT assay, with efficacy of coverage, intensity of rejection at day 8, and delay of wound healing in a xenograft model using human fresh skin (FS) and cryopreserved skin (CPS) on murine recipients (n = 49). Cryopreserved grafts were less rejectable than fresh grafts, with statistically significant different delays (P = .0008). Mice that had received grafts healed with delays; the delays, whether associated with fresh grafts or cryopreserved grafts, were not statistically significant. On day 8 after the graft, the overall damage score for the tissue's histological architectural integrity was higher for FS. Furthermore, flow cytometry analysis showed a significant increase in the number of CD4 and CD8 T-cells (P = .001) in the spleens of FS-grafted mice. These results confirm that the use of viable CPS does not change the potential for healing.


ALPL regulates the aggressive potential of high grade serous ovarian cancer cells via a non-canonical WNT pathway.
The ALPL gene is linked to hypophosphatasia, a rare genetic disease. Owing to the inverse relationships between ALPL expression and both the International Federation of Gynecology and Obstetrics (FIGO) stages and histological grades assigned to patients with serous ovarian cancer (SOC), this study was designed to explore the role and possible mechanisms of ALPL in cell motility of high grade SOC (HGSOC). The effects of ALPL overexpression on migration and invasion were detected in HGSOC cell lines SKOV3 and HEY. Gene ontology analysis for differential genes with ALPL overexpression identified several biological processes, including EMT, correlated with cell motility. Genes potentially implicated in EMT and associated with ALPL were screened using The Cancer Genome Atlas (TCGA) database. The WNT receptor Frizzled2 (FZD2) was identified and its role in HGSOC cell motility and survival was investigated. It was found that forced expression of ALPL could inhibit migration, invasion, and EMT in HGSOC cells. It also reduced the expression of FZD2 and its ligand WNT5A, accompanied by suppressed expression of their downstream target phosphorylated-STAT3 (pSTAT3). These effects were initiated via the FZD2 knockdown using siRNA and reversed by recombinant WNT5A protein. The relationship between FZD2 expression and poor HGSOC patient survival was also investigated. This data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis, a non-canonical WNT pathway for promoting EMT progression, which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.


Entamoeba histolytica: a method for isolate identification.
The ability to identify individual isolates of Entamoeba histolytica Schaudinn 1903 (Emend. Walker 1911) is necessary before several important epidemiological questions can be answered. We have developed such a method based on our discovery of extensive polymorphism in two E. histolytica genes--the serine-rich antigen gene and the "strain specific gene"--each of which has an internal tandemly repeated structure. Using the polymerase chain reaction we detected both size and restriction site polymorphisms in the repetitive regions. When the two genes were used in combination we obtained 16 distinct DNA patterns out of 18 isolates examined. Moreover, these patterns proved to be stable under a variety of conditions--long-term culture, axenization, cell cloning, and animal passage.


[Medical rehabilitation in long-term disability].
Based on data from a prospective observational cohort study the following article attempts to answer two key questions of rehabilitation research in Germany: (1) What are the utilization rates of rehabilitation measures in patients with long-term work-incapacity due to low-back pain? (2) In this group of patients: does participation in rehabilitation programs correlate with return to work? Patients with long-term work-incapacity due to low-back pain report a severely impaired health status (measured by FFbH, SF-36, numeric rating scale for pain intensity) which calls for comprehensive medical treatment and rehabilitation. 40.5% of study patients received first time medical rehabilitation between three months and one year after the beginning of long-term work-incapacity, 20.5% between one year and two years after the beginning of long-term work-incapacity. These figures were not influenced by age. Considering the severity of impairment we judge these rates as being quite low. There was no positive correlation found between utilization of medical rehabilitation measures or any other medical treatment and return to work. A positive correlation was observed for utilization of first time medical rehabilitation between three months to one year after the beginning of long-term work-incapacity and functional capacity. This effect was demonstrable for patients 50 years of age or younger. (1) In our cohort utilization of medical rehabilitation measures in patients with low-back pain and long-term work-incapacity is quite low. This suggests a considerable amount of underutilization. (2) In order to avoid underutilization the process of accessing medical rehabilitation within the German health care system should be critically reviewed. (3) In the given context of high unemployment rates and the German early pensioning system the use of "return to work" as the main criterion to judge effectiveness of rehabilitation measures remains debatable.


Characterisation and quantification of flavonoids in Iris germanica L. and Iris pallida Lam. resinoids from Morocco.
Iris resinoid obtained from Iris germanica or Iris pallida rhizomes is widely used in the perfume industry but its chemical composition has not yet been reported. Nevertheless, very active compounds have been identified in iris rhizomes including iridals and isoflavones. In this first study concerning iris resinoid composition, flavonoids were qualitatively and quantitatively investigated in I. germanica and I. pallida resinoids. Resinoids were first fractionated by reverse-phase flash chromatography in order to obtain fractions containing all isoflavones. These fractions were analysed by HPLC-DAD (diode array detector) and the fractions containing isoflavones were analysed by HPLC-QTOF (quadrupole time of flight)-MS. Then, the main isoflavones were isolated and identified by NMR and high-resolution mass spectroscopy (HRMS). Finally, total and individual isoflavones were quantified by HPLC-DAD at 265 nm using an external calibration method with irigenin as the external standard. Eight isoflavones were identified in both resinoids (irigenin, iristectorigenin A, nigricin, nigricanin, irisflorentin, iriskumaonin methyl ether, irilone, iriflogenin), one isoflavone only was identified in I. germanica resinoid (irisolidone), whereas one isoflavone (8-hydroxyirigenin), one isoflavanone (2,3-dihydroirigenin) and one benzophenone (2,6,4'-trihydroxy-4-methoxybenzophenone) only were identified in I. pallida resinoid. Isoflavones were quantified in I. germanica and I. pallida resinoids at 180 ± 1.6 mg/g and 120 ± 3.3 mg/g respectively. The study shows that I. germanica and I. pallida resinoids are rich in flavonoids and that these two Iris species can be distinguished by simply analysing the polyphenol fraction.


Common variable immunodeficiency: different faces of the same disease.
Common variable immunodeficiency (CVID) is one of the primary humoral immunodeficiencies. Despite the inborn nature, the first symptoms may appear in both children and adults. It is characterized by hypogammaglobulinaemia, severe infections, autoimmunity, allergies, and a predisposition to cancer. A delay in diagnosis is a significant problem: the time from the first symptoms of the disease to diagnosis and the implementation of proper treatment is usually very long. The consequence can be irreversible complications, which is why it is so important to promote knowledge on this immunodeficiency. To present the clinical and laboratory manifestation of primary immunodeficiencies such as common variable immunodeficiency. The study presents the clinical and laboratory phenotype of 14 patients diagnosed with CVID, aged 5 to 58 years. A detailed medical history was taken, and clinical symptoms, immunological test results and complications were analysed in each patient. According to the ESID guidelines, in the differential diagnosis process of CVID the secondary hypogammaglobulinaemia was excluded. The follow-up period ranged from 39 to 133 months (median: 79 months). The median delay for the entire group was 5 years, which was shorter in children than in adults. In the presented group, the infectious phenotype (pneumonia, sinusitis) was dominant. Autoimmune and allergic diseases, malignant tumours and enteropathies have also been observed. The diagnostic delay is still too long, especially in adults, which can lead to serious and irreversible complications. Early diagnosis and appropriate treatment with intravenous and subcutaneous immunoglobulins reduces the frequency of infections and their potential complications.


Anti-Epstein-Barr virus antibodies in systemic lupus erythematosus.
Sera from 18 patients with Systemic Lupus Erythematosus (SLE), 20 with nonA-nonB acute hepatitis and 19 healthy subjects were tested for the presence of antibodies to the viral capside of Epstein-Barr virus. In patients with SLE the mean titre of anti-VCA IgG was significantly higher than in normal subjects (p less than 0.02), and the percentage of patients with titres greater than 1:160 was significantly higher than in normal population (p less than 0.01). These high anti-VCA) titres in SLE patients are probably related to a defective immune surveillance.


Descriptive characteristics of callers to an emotional support and suicide prevention helpline in Bangladesh (first five years).
Although crisis helplines are an established method of suicide prevention, there is little research on their operation in developing countries. This paper reviews calls (N = 14,344) to the only suicide prevention hotline in Bangladesh during the first five years of the helpline's operation. Call characteristics were recorded on checklists, compiled, and analyzed. Results indicate that callers are about half male, mostly between the ages of twenty and thirty-nine, and mostly not suicidal. Callers display a wide range of reasons for calling, with relationship issues, mental illness/substance abuse, and emotions constituting the majority of calls.


Cellular transglutaminase. The particulate-associated transglutaminase from chondrosarcoma and liver: partial purification and characterization.
A transglutaminase from the malignant chondrocytes, rat swarm chondrosarcoma cells, was partially purified and characterized in an effort to understand transformation-induced changes in its activity. This enzyme separated by DE52 column chromatography after extraction from the particulate fraction of cell lysate was found to be distinct from previously characterized transglutaminases in its electrophoretic mobility, molecular size, substrate specificity, and immunologic reactivity. This enzyme was identified as a transglutaminase by its catalysis of amine (putrescine, spermine) incorporation at the carboxamide group of protein-bound gamma-glutamyl residues, and accordance of its kinetic data with the modified double displacement mechanism described for other transglutaminases. Limited proteolysis of the isolated enzyme resulted in a 3-4-fold increase of catalytic activity and a concomitant reduction of molecular size by approximately one-half. Incubation of labeled amine with chondrosarcoma cell lysate resulted in labeling of only a few proteins that appeared to be extensively cross-linked and that were located mostly in the particulate fraction of the cells. Transglutaminase extracted from the rat liver particulate fraction displayed enzymatic and structural properties closely resembling those of the enzyme from chondrosarcoma cells.


Chinese medicine shensongyangxin is effective for patients with bradycardia: results of a randomized, double-blind, placebo-controlled multicenter trial.
To evaluate the efficacy and safety of Shensong Yangxin (SSYX) in patients with bradycardia arrhythmias, a randomized, double-blind, and placebo-controlled study was conducted. Patients with bradycardia were randomly assigned to receive either SSYX (trial group, n = 115) or placebo (control group, n = 104) for 4 weeks. ECG, 24-hour continuous ECG recording, echocardiography, and hepatic and renal function were evaluated at baseline and after treatment. Results showed that the average heart rate, the fastest heart rate, and the lowest heart rate in the trial group were all significantly higher than those in the control group at the end of treatment (P < 0.05 or 0.01, resp.). Compared with pretreatment, the average heart rate, the fastest heart rate, and the lowest heart rate in the trial group all increased significantly after treatment (P < 0.05 or 0.01, resp.). Both the efficacy and the symptom scores in the trial group were significantly better than those in the control group after treatment (both having P < 0.01). No severe adverse effects were reported. In conclusion, SSYX treatment significantly increased the heart rate in patients with bradycardia without severe side effects. The exact mechanisms remain to be further explored.


[Variation in HLA-B27 gene subtypes and susceptibility of ankylosing spondylitis in the Croatian population].
The differences in amino acid residues of HLA-B27 subtypes are minor, but may play role in pathogenesis of ankylosing spondylitis (AS). Aim of this study was to investigate of frequency of B27 subtypes in Croatian AS patients and B27 positive healthy controls. Group of 50 AS patients and 38 B27 positive controls were typed for B27 subtypes by PCR-SSP method. In the group of AS patients we found four subtypes: B*2705 (83.0%), B*2702 (13.2%), while remaining two alleles B*2701 and B*2704 had one individual each. In the group of B27+ controls we also observed B*2705 (76.3%) as most frequent allele while frequency of B*2702 was 21.1%. No significant evidence for association between AS and a particular HLA-B27 subtype in the Croatian population were found.


Does Intensive Training of Attention Influence Cognitive Fatigability in Patients With Acquired Brain Injury?
Impairments in attention and the speed of information processing are central to the experience of cognitive fatigue in patients with acquired brain injury (ABI). Attention may be improved through intensive training in a rehabilitation setting. The aim of the study was to investigate the feasibility of reducing cognitive fatigability (CF) using attention training and to explore the effect of two different approaches to attention training. Randomised controlled study in a rehabilitation setting. 59 patients (age 19-59 years) with mild to moderate stroke or traumatic brain injury in the early (<4 month) phase. Patients were randomly assigned to intensive specific training with Attention Process Training (APT) or Activity-Based Attention Training (ABAT) for 3-5 days per week for a period of 5-6 weeks with a total of 20 h, in addition to traditional interdisciplinary rehabilitation. CF was conceptualised as performance decline in terms of an increased number of incorrect responses between the first and the last quintiles of the Paced Auditory Serial Addition Test (PASAT). A negative result was defined as fatigability. The evaluator of fatigability was blinded to treatment. At baseline, there were no differences between the groups in age, education, reasoning, anxiety or depression. After training, a significant treatment effect was found (p = 0.020), as the APT-group, but not the ABAT-group, had improved. However, after controlling for baseline differences regarding CF on the PASAT-f, the difference was no longer significant. The results indicate that cognitive training might be a feasible method for reducing CF through attention training and that patients with high levels of CF benefit most from attention training. The type of intervention provided, whether specific or activity-based attention training, appears to be of less importance, as there was no treatment effect after controlling for the baseline level of CF. Future studies are required to confirm the validity of the findings.


Improving Pathological Assessment of Breast Cancer by Employing Array-Based Transcriptome Analysis.
Breast cancer research has paved the way of personalized oncology with the introduction of hormonal therapy and the measurement of estrogen receptor as the first widely accepted clinical biomarker. The expression of another receptor-HER2/ERBB2/neu-was initially a sign of worse prognosis, but targeted therapy has granted improved outcome for these patients so that today HER2 positive patients have better prognosis than HER2 negative patients. Later, the introduction of multigene assays provided the pathologists with an unbiased assessment of the tumors' molecular fingerprint. The recent FDA approval of complete microarray pipelines has opened new possibilities for the objective classification of breast cancer samples. Here we review the applications of microarrays for determining ER and HER2 status, molecular subtypes as well as predicting prognosis and grade for breast cancer patients. An open question remains the role of single genes within such signatures. Openly available microarray datasets enable the execution of an independent cross-validation of new marker and signature candidates. In summary, we review the current state regarding clinical applications of microarrays in breast cancer molecular pathology.


Adverse reactions of drugs specifically used for treatment of SARS-CoV-2 infection.
Currently, there is no treatment approved for COVID-19. Numerous drugs are being used in an empirical manner according to experience and availability. Studies demonstrating their efficacy and safety are still to be published. Thus, it is of vital importance for healthcare workers to be well informed and updated regarding possible immunological and non-immunological adverse effects regarding such treatments. In this narrative revision, the rationale use of these treatments in the SARS-CoV-2 infection is emphasized as well as their most frequently described adverse drug reactions. Drugs that are being essayed to counteract both clinical phases that are thought to take place in the severe stage of this disease are included; an initial phase where a viral infection prevails and a second phase where an inflammatory response takes over. Adverse reactions registered in the Pharmacovigilance Program of our hospital before the onset of this pandemic have also been included.


Comparison of Patterns of Accumulation of Ribulose Bisphosphate Carboxylase Antigen and Catalytic Activity and Measurement of Antigen Half-Life during the Cell Cycle of Chlorella sorokiniana.
By use of specific immunochemical procedures, ribulose-1,5-bisphosphate carboxylase (RuBPCase), antigen and catalytic activity were shown to have coincident step-patterns of accumulation during the cell cycle of Chlorella sorokiniana. Pulse-chase studies, employing radioactive sulfate, were performed during the period of rapid accumulation of enzyme activity and during the period of constant enzyme activity in the cell cycle. No degradation of RuBPCase antigen could be detected during either of these cell cycle periods. Thus, the step-pattern of accumulation of RuBPCase activity resulted from periodic synthesis of an enzyme that was stable under steady-state cell cycle conditions. Although inhibition of protein synthesis by cycloheximide, at different times in the cell cycle in the light, resulted in rapid decay of RuBPCase activity, this loss in activity occurred without detectable loss in enzyme antigen. When synchronous cells were placed into the dark, to slow the rate of protein synthesis in the absence of cycloheximide, the levels of enzyme antigen and activity decreased by 30 and 50%, respectively, during the 10-hour dark period. Thus, in C. sorokiniana changes in RuBPCase activity do not necessarily reflect parallel changes in enzyme antigen, particularly when cell growth is perturbed by changes from steady-state cultural conditions.


When family-centered care is challenged by infectious disease: pediatric health care delivery during the SARS outbreaks.
In this ethnographic study, the authors examined the experiences and perspectives of children hospitalized because of SARS (severe acute respiratory syndrome), their parents, and pediatric health care providers. The sample included 5 children, 10 parents, and 8 health care providers who were directly affected by SARS during the time of the outbreaks and extreme infection control procedures. The data analyses illuminated a range of perceived experiences for this triadic sample. Issues related to social isolation due to infection control precautions were predominant. Themes included emotional upheaval, communication challenges, and changes in parental and professional roles. These findings reveal the cogent effects of SARS on family-centered care. The notion of providing family-centered care within an environment plagued by an infectious outbreak suggests an omniously difficult task. Efforts must be made to optimize family-centered care despite obstacles. The authors suggest effective clinical approaches in the event of future outbreaks.


Crystallization and preliminary X-ray diffraction studies of a protein disulfide oxidoreductase from Aquifex aeolicus.
A protein disulfide oxidoreductase from the thermophilic bacterium Aquifex aeolicus has been overexpressed in Escherichia coli and crystallized at 298 K using the hanging-drop vapour-diffusion method. Crystals belong to space group R32, with unit-cell parameters a = b = 161.1, c = 153.1 A. A complete data set has been collected to 2.4 A using synchrotron radiation. Packing-density considerations agree with the presence of 2-4 monomers in the asymmetric unit, with a corresponding solvent content of 66-32%.


Ligand effects on the [Cu(PhO)(PhOH)]+ redox active complex.
Under gas phase conditions, the [Cu(PhO)(PhOH)](+) complex is composed of copper(I), a phenoxy radical bound via the oxygen atom, and a phenol bound via the aromatic ring. Effects of additional ligand coordination on the molecular and electronic structure of the complex [Cu(PhO)(PhOH)](+) are investigated by mass spectrometric and quantum chemical means for [Cu(PhO)L](+) (L = H(2)O, CH(3)OH, tetrahydrofuran, NH(3), pyridine, imidazole, 1,2-dimethoxyethylene, N,N,N',N'-tetramethylethylenediamine, pyrrole, and thiophene) and [Cu(PhO)(PhOH)L(n)](+) (L = H(2)O, NH(3), and 4-methylimidazole) models. The nature and number of additional ligands critically influences the spin distribution in the complex, which is sensitively reflected by the phenoxy CO stretching mode.


[Blood lead in the inhabitants of 4 Peruvian localities].
During 1994 and 1995, a cross-sectional study was carried out to investigate the concentrations of lead in the blood of inhabitants of four Peruvian cities (Lima, Huancayo, La Oroya, and Yaupi) with different population densities and degrees of industrial development. In a random sample of 180 men and 180 women without occupational exposure to lead, blood lead levels were measured by the atomic absorption method with a Perkin Elmer 603 spectrophotometer without a graphite oven. The results revealed blood lead concentrations of 269 +/- 63 micrograms per liter (micrograms/L) in Lima, 224 +/- 47 micrograms/L in Huancayo; 348 +/- 40 micrograms/L in La Oroya, and 140 +/- 27 micrograms/L in Yaupi. It was concluded that blood lead levels in the inhabitants of these cities were related to the degree of industrialization and the population density of each locality.


More research on the pill and alternative methods (of contraception).
More research on the pill and alternative methods of contraception was urged by Ralph Nader's Health Research Group (HRG), which also recommended that the Food and Drug Administration develop a new patient package insert for all forms of contraceptives, including nonprescription methods. The group also said the government and drug companies should share the cost of long-term follow-up studies of the effects on health of the pill and other birth control methods. The recommendations followed presentations at an HRG forum from NIH scientists and S. Ramcharan, principal investigator of the Walnut Creek (California) Contraceptive Study supported by the National Institute of Child Health and Human Development. Ramcharan studied 15,000 women over 10 years and found cervical cancer incidence of 173/100,000 person years for women who used the pill for more than 4 years, compared with a rate of 32/100,000 for women who never used the pill. Ramcharan declined to draw any cause-effect conclusions based on these results, stating they were "confounded" by possible differences in sexual activity between the 2 groups. She said a preliminary case comparison study to adjust for these differences "suggests sexual behavior may account for some, but not all," of the 5-fold increase in cervical cancer incidence among pill users. HRG director S. Wolfe said enough data exists to state a relationship between the pill and cervical cancer. "There's no other explanation for the increase," he said, adding that Ramcharan had controlled for the effects of age, education, marital status, number of Papanicolaou smears, religion, number of pregnancies, a history of genital infections, and smoking. Forum participants urged more research on contraceptive devices and drugs now in use, long-term effects of sterilization, value of condoms and spermicides in preventing VD, and development of a patient package insert for all forms of contraception stating the relative effectiveness and risks of each. The group discussed the need for long-term funding of follow-up studies, and suggested that drug companies be required to pay for at least some of the pre- and postmarketing research.


Annealing-Insensitive, Alcohol-Processed MoOx Hole Transport Layer for Universally Enabling High-Performance Conventional and Inverted Organic Solar Cells.
At present, most solution-processed molybdenum oxide (s-MoOx) hole transport layers (HTLs) are still mainly used in conventional organic solar cells (OSCs) but unsuitable for inverted OSCs. Herein, we demonstrate for the first time an annealing-insensitive, alcohol-processed MoOx HTL that can universally enable high-performance conventional and inverted OSCs. The s-MoOx HTL is spin-coated from the MoOx nanoparticle dispersion in alcohol, where the MoOx nanoparticles are synthesized by simple nonaqueous pyrolysis conversion of MoO2(acac)2. The MoOx nanoparticles possess uniform and very small sizes of less than 5 nm and can be well dispersed in alcohol, so the s-MoOx HTLs on ITO and active layer both show an overall uniform and smooth surface, suitable for conventional and inverted OSCs. In addition, the s-MoOx HTL possesses decent optical transmittance and appropriate work function. Utilizing the s-MoOx HTL annealed between room temperature and 110 °C and PM6:Y6 active layer, the conventional OSCs show an excellent power conversion efficiency (PCE) of 16.64-17.09% and the inverted OSCs also show an excellent PCE of 15.74-16.28%, which indicate that the s-MoOx HTL could be annealing-insensitive and universal for conventional and inverted OSCs. Moreover, conventional and inverted OSCs with the s-MoOx HTLs annealed at 80 °C both exhibit optimal PCEs of 17.09 and 16.28%, respectively, which are separately superior than that of the PEDOT:PSS-based conventional OSCs (16.94%) and the thermally evaporated MoO3 (e-MoO3)-based inverted OSCs (16.03%). Under light soaking and storage aging in air, the unencapsulated inverted OSCs based on the s-MoOx HTL show similarly excellent ambient stability compared to the e-MoOx-based devices. In addition, the s-MoOx HTL also shows a universal function in conventional and inverted OSCs with PBDB-T:ITIC and PM6:L8-BO active layers. Notably, the s-MoOx-based conventional and inverted OSCs with the PM6:L8-BO active layer exhibit very excellent PCEs of 18.21 and 17.12%, respectively, which are slightly higher than those of the corresponding PEDOT:PSS-based device (18.17%) and e-MoO3-based device (17.00%). The annealing-insensitive, alcohol-processed MoOx HTL may be very promising for flexible and large-scale processing conventional/inverted OSCs.


Expanding the scope of human DNA polymerase λ and β inhibitors.
The exact biological functions of individual DNA polymerases still await clarification, and therefore appropriate reagents to probe their respective functions are required. In the present study, we report the development of a highly potent series of human DNA polymerase λ and β (pol λ and β) inhibitors based on the rhodanine scaffold. Both enzymes are involved in DNA repair and are thus considered as future drug targets. We expanded the chemical diversity of the small-molecule inhibitors arising from a high content screening and designed and synthesized 30 novel analogues. By biochemical evaluation, we discovered 23 highly active compounds against pol λ. Importantly, 10 of these small-molecules selectively inhibited pol λ and not the homologous pol β. We discovered 14 small-molecules that target pol β and found out that they are more potent than known inhibitors. We also investigated whether the discovered compounds sensitize cancer cells toward DNA-damaging reagents. Thus, we cotreated human colorectal cancer cells (Caco-2) with the small-molecule inhibitors and hydrogen peroxide or the approved drug temozolomide. Interestingly, the tested compounds sensitized Caco-2 cells to both genotoxic agents in a DNA repair pathway-dependent manner.


Voluntary Binge Consumption of Ethanol in a Sweetened, Chocolate-Flavored Solution by Male and Female Adolescent Sprague Dawley Rats.
The still maturing adolescent brain may be particularly vulnerable to lasting consequences of ethanol (EtOH) exposure. Yet, human adolescents are the age group most likely to engage in binge drinking (a pattern of drinking leading to blood EtOH concentrations (BECs) of 80 mg/dl or greater). Most studies to date assessing the long-term effects of adolescent EtOH exposure in outbred rodent populations have either used experimenter-administered EtOH to produce BECs in the binge range or assessed voluntary intake of EtOH at well below binge levels. Beginning with a modified schedule-induced polydipsia (SIP) procedure, this study examined the suitability of several approaches to induce voluntary binge-like consumption during adolescence in an outbred rat strain. Adolescent male and female Sprague Dawley rats were food deprived to 85% projected free-feeding weights beginning on postnatal day (P) 24 and were given 30 minutes of access to 10% EtOH in chocolate Boost® or Boost® alone daily from P28 to P41 (followed later by their daily allocation of food). Animals were tested within operant chambers (Exp. 1a, 1b and Exp. 2) or home and novel cages (Exp. 3). Animals received either scheduled delivery of banana pellets to examine SIP (Exp. 1a,b) or massed pellet presentation (Exp. 2 and Exp. 3). Blood samples were collected via the lateral tail vein on P33 and P41. Intakes produced BECs frequently in the binge range (>80 mg/dl) and modeled binge-like consumption patterns, with high consumption days typically followed by 1 to 2 days of lower consumption; this variability was less evident with Boost® alone. Consumption was not schedule induced and was generally high across all studies, although consumption in males appeared to be particularly pronounced when animals were tested in the presence of their cage mate. Binge-like patterns of EtOH consumption were produced using these procedures in adolescent Sprague Dawley rats of both sexes and may prove to be a useful model for work examining the short- and long-term consequences of high levels of voluntary EtOH intake in adolescence.


Phytochemical Profiling, GC-MS Analysis and α-Amylase Inhibitory Potential of Ethanolic Extract of Cocos nucifera Linn. Endocarp.
Drugs with post-prandial action constitute one of the main courses of treatments for diabetes. In the present investigation, we have explored the α-amylase inhibitory potential of ethanolic extract of Cocos nucifera endocarp. DNS based assay was done to assess the α-amylase inhibition potential of ethanolic extract. Phytochemical screening and GC-MS analysis were done in order to assess the chemical profiling of extract. In silico docking studies were done using VLife MDS 4.6 software and the probable molecules, predicted after GC-MS analysis, were docked with the co-crystallized (acarbose) tracked active site and rest all cavities of porcine pancreatic α-amylase (1OSE). ADMET analysis was done using StarDrop 6.4, Derek Nexus and P450 Modules from Optibrium Ltd. and LHASA Ltd. DNS based α-amylase assay indicated that the IC50 value of extract lies in the range of 63- 126 µg/ml and at higher doses, i.e. above 250 µg/ml, it has better α-amylase inhibition than the standard drug, acarbose. Phytochemical screening indicated that ethanolic extract is rich in alkaloids, tannins, flavonoids, saponins, triterpenes, glycosides, carbohydrates, terpenoids, quinones and lactones. Further, GC-MS analysis (where Similarity Index was > 90) predicted that the probable phytoconstituents present in the ethanolic extract are myristic acid, syringaldehyde, eugenol, vanillin, 2,4-di-tert-butylphenol, lauric acid, palmitic acid methyl ester and γ-sitosterol. γ-Sitosterol showed the strong affinity towards the active site which was tracked by a co-crystallized ligand along with cavity 1 and 2 while significant interactions were observed in case of co-crystallized tracked active site as well as cavity 4 of 1OSE. Ethanolic extract of C. nucifera has no hemolytic effect. Its ability to effectively inhibit α-amylase may be attributed to the presence of the above probable molecules, which will be explored further.


Protein adaptations in archaeal extremophiles.
Extremophiles, especially those in Archaea, have a myriad of adaptations that keep their cellular proteins stable and active under the extreme conditions in which they live. Rather than having one basic set of adaptations that works for all environments, Archaea have evolved separate protein features that are customized for each environment. We categorized the Archaea into three general groups to describe what is known about their protein adaptations: thermophilic, psychrophilic, and halophilic. Thermophilic proteins tend to have a prominent hydrophobic core and increased electrostatic interactions to maintain activity at high temperatures. Psychrophilic proteins have a reduced hydrophobic core and a less charged protein surface to maintain flexibility and activity under cold temperatures. Halophilic proteins are characterized by increased negative surface charge due to increased acidic amino acid content and peptide insertions, which compensates for the extreme ionic conditions. While acidophiles, alkaliphiles, and piezophiles are their own class of Archaea, their protein adaptations toward pH and pressure are less discernible. By understanding the protein adaptations used by archaeal extremophiles, we hope to be able to engineer and utilize proteins for industrial, environmental, and biotechnological applications where function in extreme conditions is required for activity.


Provocative discography in low back pain patients with or without somatization disorder: a randomized prospective evaluation.
Recent reports of provocative discography not only instill confusion, but also create numerous questions about its value in evaluating low back pain. It was reported that provocative discography produced pain in patients who were not suffering with low back pain but suffering with somatization disorder and depression. This study was designed to evaluate 50 randomly assigned patients, with 25 patients in Group I without somatization disorder and 25 patients in Group II with diagnosis of somatization disorder. In addition, depression, generalized anxiety disorder and combinations thereof were also evaluated. All patients underwent discography, investigating two to three discs in each patient. All studies included a control level with a disc that did not produce the patient's pain upon injection of contrast medium. Provocation with exact pain reproduction concordant with the symptom complex upon injection of contrast into the disc was considered positive. Any other response, with or without pain, was considered negative. Results showed positive provocative discography in 46% of the patients in the somatization group compared to 54% in the non-somatization group; in 46% of patients with depression compared to 54% of patients without depression; in 15 of 30 patients with generalized anxiety disorder; in 11 of 20 patients without generalized anxiety disorder; and in 42% of patients with combined somatization and depression, with negative discography in 58% of the patients. It is concluded that provocative discography provides similar results in patients with or without somatization, with or without depression, with somatization but with or without depression or with other combinations of the psychological triad of somatization disorder, depression, and generalized anxiety disorder.


Insect infection model for Campylobacter jejuni reveals that O-methyl phosphoramidate has insecticidal activity.
Galleria mellonella (wax moth) larvae have elsewhere been shown to be susceptible to pathogens such as Francisella tularensis, Burkholderia mallei, and Pseudomonas aeruginosa. We report that the larvae are rapidly killed by Campylobacter jejuni at 37C. Three strains of C. jejuni tested, 11168H (human diarrheal isolate), G1 (human Guillain-Barré syndrome isolate), and 81-176 (human diarrheal isolate), were equally effective at killing G. mellonella larvae. A panel of defined mutants of C. jejuni 11168H, in known or putative virulence genes, showed different degrees of attenuation in G. mellonella larvae. A mutant lacking the O-methyl phosphoramidate (MeOPN) capsule side group was attenuated, clearly demonstrating that MeOPN has a role in virulence. This new model of C. jejuni infection should facilitate the identification of novel virulence genes.


Object segmentation of database images by dual multiscale morphological reconstructions and retrieval applications.
Processing images for specific targets on a large scale has to handle various kinds of contents with regular processing steps. To segment objects in one image, we utilized dual multiScalE Graylevel mOrphological open and close recoNstructions (SEGON) to build a background (BG) gray-level variation mesh, which can help to identify BG and object regions. It was developed from a macroscopic perspective on image BG gray levels and implemented using standard procedures, thus robustly dealing with large-scale database images. The image segmentation capability of existing methods can be exploited by the BG mesh to improve object segmentation accuracy. To evaluate the segmentation accuracy, the probability of coherent segmentation labeling, i.e., the normalized probability random index (PRI), between a computer-segmented image and the hand-labeled one is computed for comparisons. Content-based image retrieval (CBIR) was carried out to evaluate the object segmentation capability in dealing with large-scale database images. Retrieval precision-recall (PR) and rank performances, with and without SEGON, were compared. For multi-instance retrieval with shape feature, AdaBoost was used to select salient common feature elements. For color features, the histogram intersection between two scalable HSV descriptors was calculated, and the mean feature vector was used for multi-instance retrieval. The distance measure for color feature can be adapted when both positive and negative queries are provided. The normalized correlation coefficient of features among query samples was computed to integrate the similarity ranks of different features in order to perform multi-instance with multifeature query. Experiments showed that the proposed object segmentation method outperforms others by 21% in the PRI. Performing SEGON-enabled CBIR on large-scale databases also improves on the PR performance reported elsewhere by up to 42% at a recall rate of 0.5. The proposed object segmentation method can be extended to extract other image features, and new feature types can be incorporated into the algorithm to further improve the image retrieval performance.


Comparative morphophysiological evaluation of the testis of adult Wistar rats fed low protein-energy diet and dosed with aqueous extracts of Cuscuta australis.
Cuscuta australis (C. australis) seed and stem are historically used by the local population as dietary supplement for the management of infertility. This study, therefore, evaluated the effect of orally administered aqueous extracts of C. australis seed and stem, 300 mg/kg body weight/day for seven days, on the testis of the adult Wistar rat fed either low or normal protein-energy diets. The control group received water. The relative weight of the testis was non-significantly increased (p>0.05) in the Low Protein-energy diet-Water-treated (LPWA), Low Protein-energy diet-Seed-treated (LPSE) and Normal Protein-energy diet-Seed-treated (NPSE) groups relative to the Normal Protein-energy diet-Water-treated (NPWA). The weight of the testis was also non-significantly increased (p˃0.05) in the Low Protein-energy diet-Stem-treated (LPST), but decreased in the Normal Protein-energy diet-Stem-treated (NPST), relative to LPWA and NPWA. Heights of germinal epithelium were significantly decreased (p<0.05) in the LPWA, LPSE and LPST relative to the NPWA, NPSE and NPST. Diet significantly influenced (p<0.001) the effect of stem extract on the height of germinal epithelium. The NPSE, LPSE, NPST, LPST and LPWA showed significantly decreased (p<0.001) plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) relative to NPWA. The LPWA, LPSE and NPST also showed significantly decreased (p<0.001) levels of testosterone relative to NPWA and LPST. Diet significantly influenced (p<0.001) the effect of seed on the level of LH. Seed-diet interactions significantly affected the levels of FSH (p<0.001) and LH (p<0.05), but not testosterone. Diet significantly influenced (p<0.001) the effects of stem extract on the levels of FSH, LH and testosterone. Stem-diet interactions significantly affected (p<0.001) the levels of FSH, LH and testosterone. Our data suggest that the aqueous extract of C. australis stem is more potent than the seed extract and that dietary protein-energy intake may influence the efficacy of orally administered aqueous extracts of C. australis.


A 10-year retrospective analysis of the clinical profile and outcomes of infective endocarditis at a tertiary hospital in KwaZulu-Natal, South Africa.
To examine the clinical profile and treatment outcomes of infective endocarditis (IE) at a tertiary hospital in KwaZulu-Natal. A 10-year retrospective analysis was conducted on cases of definite IE (modified Duke criteria). Ninety-seven subjects (HIV infected, n = 12) satisfied the study criteria (mean age 29.7 ± 15.6 years, M:F 1.4:1). Underlying rheumatic heart disease was present in 84.5% and severe dyspnoea in 67.0% of cases. Staphylococcus aureus was the commonest pathogen isolated (18.6%). Heart failure was present in 61.9% and vegetations were identified in 85 (87.6%) subjects, resulting in 41 (42.3%) embolic events. The clinical profile and outcomes were similar in the HIV-positive and -negative patients. Surgery was performed in 73 subjects (surgical mortality rate 9.5%, total mortality rate 26.4%). Multivariate analysis identified acute-onset IE [odds ratio (OR) 251.46, 95% confidence interval (CI) 1.18-5343.63, p = 0.043], vegetation size > 15 mm (OR 222.60, 95% CI 1.04-4730.34, p = 0.043) and medical management only (OR 20.89, 95% CI 2.12-200.06, p = 0.037) as predictors for increased in-hospital mortality. IE affects young people with underlying rheumatic heart disease and is associated with high morbi-mortality attributable to advanced disease at presentation and to haemodynamic failure resulting from valve destruction due to acute onset of aggressive infection.


Bile ductal and ductular changes of the livers in the renal allografted patients.
Nine liver biopsies from six renal allografted patients suffering from liver injury were examined by light and electron microscope and immunostaining. The patients had never been on liver dysfunction prior to renal transplantation and after renal transplantation had been administered azathioprine continuously. These patients had shown HBs antigen negative sera. Three of these patients restored normal liver function after withdrawal of azathioprine. Accordingly, the liver diseases of the three were supposedly caused by azathioprine. The liver biopsies of six patients were histologically diagnosed as follows: chronic active hepatitis with severe cholestasis (1 patient), liver cirrhosis with cholestasis (1 patient), acute hepatitis (1 patient), and mild hepatitis (3 patients). The common pathological findings of six patients were degeneration of interlobular bile ducts and ductules, as well as degeneration of liver cells, and mild to moderate inflammatory cell infiltration of portal tracts and sinusoids. The degeneration of bile ductal and ductular cells were classified into two types: light microscopical finding showed vacuolar or eosinophilic cytoplasm and electron microscopic compatible findings showed hydropic cytoplasm scant of free ribosome and organelles, or dense cytoplasm rich in free ribosome and degenerated organelles. The basement membranes of interlobular bile ducts and ductules were always preserved.


Limited progress in nutrient pollution in the U.S. caused by spatially persistent nutrient sources.
Human agriculture, wastewater, and use of fossil fuels have saturated ecosystems with nitrogen and phosphorus, threatening biodiversity and human water security at a global scale. Despite efforts to reduce nutrient pollution, carbon and nutrient concentrations have increased or remained high in many regions. Here, we applied a new ecohydrological framework to ~12,000 water samples collected by the U.S. Environmental Protection Agency from streams and lakes across the contiguous U.S. to identify spatial and temporal patterns in nutrient concentrations and leverage (an indicator of flux). For the contiguous U.S. and within ecoregions, we quantified trends for sites sampled repeatedly from 2000 to 2019, the persistence of spatial patterns over that period, and the patch size of nutrient sources and sinks. While we observed various temporal trends across ecoregions, the spatial patterns of nutrient and carbon concentrations in streams were persistent across and within ecoregions, potentially because of historical nutrient legacies, consistent nutrient sources, and inherent differences in nutrient removal capacity for various ecosystems. Watersheds showed strong critical source area dynamics in that 2-8% of the land area accounted for 75% of the estimated flux. Variability in nutrient contribution was greatest in catchments smaller than 250 km2 for most parameters. An ensemble of four machine learning models confirmed previously observed relationships between nutrient concentrations and a combination of land use and land cover, demonstrating how human activity and inherent nutrient removal capacity interactively determine nutrient balance. These findings suggest that targeted nutrient interventions in a small portion of the landscape could substantially improve water quality at continental scales. We recommend a dual approach of first prioritizing the reduction of nutrient inputs in catchments that exert disproportionate influence on downstream water chemistry, and second, enhancing nutrient removal capacity by restoring hydrological connectivity both laterally and vertically in stream networks.


An experimental and theoretical study of spin-spin coupling in chlorosilanes.
An experimental and theoretical study of the absolute value of the one-bond spin-spin coupling constant |(1)J(Si,H)| in SiH(n)Cl(4-n) (n = 0-4) dissolved in THF-d(8) is presented. We found |(1)J(Si,H)| to increase with an increasing number of chlorine substituents, and the quantitative changes were found to differ from the values previously reported for the same compounds dissolved in cyclohexane-d(12). We also report on the variations in |(1)J(Si,H)| as a function of temperature, which we found to be linearly temperature dependent for the chlorine-substituted silanes and temperature independent for SiH(4). Furthermore, the temperature dependence of |(1)J(Si,H)| varied between the different chlorosilanes. Solvent-solute interactions were studied by quantum chemical DFT calculations. The variations in chloro-silane bond lengths upon adduct formation and the different adduct interaction energies may explain the temperature dependences of the coupling constants.


Reactivity of anhydrous keggin-type heteropolyacids with alkylsilanes: synthesis and characterization.
Anhydrous tungstic heteropolyacids react with alkylsilanes in the absence of solvent, leading to the evolution of hydrogen and the formation of a new kind of species where silicon is only weakly interacting with the polyoxometalate. The resulting material was characterized by various physicochemical methods including NMR, IR, and Raman spectroscopy. The most interesting feature is the unusual chemical shift of the (29)Si nuclei (ca. +50 ppm), which confirms the formation of a quasi-ionic bond between the organic and inorganic moieties. The weakness of this bond was also evidenced by chemical reactivity with nBu(4)NCl (leading to the formation of R(3)SiCl species) and oxygen. This new kind of structure can be of great interest in the field of microelectronics. Indeed the reactivity described in this article can be used and transferred easily in heterogeneous conditions to introduce defects in semiconductors.


Relationship between spatial coherence of synchrotron radiation and emittance.
Analytical calculation of the first-order spatial coherence for the Gaussian beam and the exact numerical calculation for synchrotron radiation are compared in this paper. The approximation of regarding synchrotron radiation as a Gaussian beam is often used to investigate the brightness, the flux and some qualitative properties. Calculations show that synchrotron radiation does not have as high coherence as the Gaussian beam because of the beam profile, the phases of the wave and the polarization. If one can measure the beam size and the spatial coherence of synchrotron radiation, it is possible to determine the total photon beam emittance without any knowledge of the Twiss parameters of the ring.


Mechanism of enantioselection in Rh-catalyzed asymmetric hydrogenation. The origin of utmost catalytic performance.
This article describes recent developments in the understanding of the mechanism of enantioselection in one of the most efficient artificial catalytic reactions--Rh-catalyzed asymmetric hydrogenation. Numerous experimental and computational data are consistent with the idea that the enantioselection takes place through the reversible coordination of the double bond in octahedral dihydride complexes, which can happen only if the resulting chelate cycle is formed in the less hindered quadrant. In its main features, this mechanism of generating chirality resembles the recently uncovered three-stage recognition process occurring in enzymatic reactions.


Psychoeducational Psychotherapy and Omega-3 Supplementation Improve Co-Occurring Behavioral Problems in Youth with Depression: Results from a Pilot RCT.
This pilot randomized controlled trial (RCT) investigated benefits of omega-3 fatty acid supplementation and Individual-Family Psychoeducational Psychotherapy (PEP; a family-focused, cognitive-behavioral therapy) for behavior problems among youth with depression. Participants aged 7-14 with DSM-IV-TR depressive disorders (N = 72; 56.9 % male) were randomized to 1 of 4 treatment conditions: PEP + omega-3, PEP monotherapy (with pill placebo), omega-3 monotherapy, or placebo (without active intervention). At screen, baseline, and 2, 4, 6, 9, and 12 weeks post-baseline, parents completed the SNAP-IV, which assesses attention-deficit/hyperactivity disorder symptoms, oppositional defiant disorder symptoms, and overall behavior problems. At screen, baseline (randomization), 6 and 12 weeks, parents completed the Eyberg Child Behavior Inventory (ECBI), which includes Intensity and Problem scales for child behavior problems. Youth who had a completed SNAP-IV or ECBI for at least two assessments during treatment (n = 48 and 38, respectively) were included in analyses of the respective outcome. ClinicalTrials.gov.:NCT01341925. Linear mixed effects models indicated a significant effect of combined PEP + omega-3 on SNAP-IV Total (p = 0.022, d = 0.80) and Hyperactivity/Impulsivity trajectories (p = 0.008, d = 0.80), such that youth in the combined group saw greater behavioral improvement than those receiving only placebo. Similarly, youth in combined treatment had more favorable ECBI Intensity trajectories than youth who received no active treatment (p = 0.012, d = 1.07). Results from this pilot RCT suggest that combined PEP + omega-3 is a promising treatment for co-occurring behavior symptoms in youth with depression.


Migraine Treatment in Emergency Departments of Brazil: A Retrospective Study of 2 Regions.
This study describes the approaches, medications used, and time of care for migraineurs, who have been in emergency departments (ED) from 2 different regions of Brazil. Retrospective, cross-sectional, observational, non-randomized study of migraine patients seen at 2 headache centers in Brazil. Eighty-four migraine patients (15 men and 69 women) were divided into 2 groups: chronic (19%, n = 16) and episodic migraineurs (81%, n = 68). In the ED, medications were used in the following order of frequency: dipyrone or metamizole (89.3%, 75/84), nonsteroidal anti-inflammatory drugs (57.1%; 48/84) opioids (51.1%; 43/84), metoclopramide (29.8%; 25/84), dexamethasone (28.6%; 24/84), chlorpromazine (13.1%; 11/84), and subcutaneous sumatriptan (7.1%; 6/84). The average time in the care center was 8.2 hours, but only 23 patients (27.4%) left the hospital with greater than 50% relief in headache severity. Dipyrone and nonsteroidal anti-inflammatories were the most used drugs, but nearly half received opioids. More efficient drugs were poorly used. Considering the number of patients leaving the hospital with headache relief, a changing treatment paradigm should be carried out in Brazil.


Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells.
Accumulating evidence has shown that dysfunctional mitochondria can be selectively removed by mitophagy. Dysregulation of mitophagy is implicated in the development of neurodegenerative disease and metabolic disorders. How individual mitochondria are recognized for removal and how this process is regulated remain poorly understood. Here we report that FUNDC1, an integral mitochondrial outer-membrane protein, is a receptor for hypoxia-induced mitophagy. FUNDC1 interacted with LC3 through its typical LC3-binding motif Y(18)xxL(21), and mutation of the LC3-interaction region impaired its interaction with LC3 and the subsequent induction of mitophagy. Knockdown of endogenous FUNDC1 significantly prevented hypoxia-induced mitophagy, which could be reversed by the expression of wild-type FUNDC1, but not LC3-interaction-deficient FUNDC1 mutants. Mechanistic studies further revealed that hypoxia induced dephosphorylation of FUNDC1 and enhanced its interaction with LC3 for selective mitophagy. Our findings thus offer insights into mitochondrial quality control in mammalian cells.


Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease patients.
We attempted to determine whether changes in protein kinase C (PKC) activity in Alzheimer's disease (AD) brains are also present in cultured skin fibroblasts from living patients. Biopsies collected from shoulder skin were transferred to culture plates with an appropriate growth medium, and histone-directed PKC activity as well as phorbol ester binding were individually determined in soluble and particulate fractions prepared from AD and non-AD fibroblast cell lines. Binding experiments indicated that PKC was unevenly distributed between cytosol (78%) and particulate (22%). The Bmax values for phorbol ester binding in soluble and particulate fractions were similar in AD and non-AD patients. Kd values in the cytosol were 94% higher in AD patients, indicating lower affinity of the enzyme for the ligand. Accordingly, the soluble PKC activity was 30% lower in AD patients. The data suggest that the changes in PKC phosphorylating activity represent a diffuse cellular defect in AD and are not confined to the brain. The alterations of the enzyme may participate in the disregulation in processing of beta-amyloid precursor protein in AD.


Prognosis of hibernating myocardium is independent of recovery of function: evidence from a routine based follow-up study.
Revascularization of hibernating segments improves both ventricular function (VF) and survival. In this study, we determined whether this relation is true in a routine based patients population with mildly reduced VF. Two to 6 years after undergoing 201Tl scintigraphy to detect hibernation, 153 patients were interviewed in order to collect medical information. This population was divided into four groups, according to the presence or absence of myocardial hibernation and of revascularization. Age, gender and left ventricular ejection fraction (LVEF) were similar in the four groups. Hard cardiac events (HEs) were noted in 14/33 (41%) patients with uncorrected hibernation, while in the other three groups HEs were recorded in fewer than 3% of patients. Univariate analysis indicated that the presence of hibernation, regardless of its extension, was the highest significant predictor of HEs. Multivariate analysis indicated that hibernation, stress ischaemia, age and absence of revascularization were significant predictors of HEs. These findings were not related to changes in LVEF or to New York Heart Association (NYHA) class during follow-up. In this routine based patient population, with mildly reduced VF, the rate of HEs seems to be related to uncorrected hibernation regardless of its extension. In these patients revascularization of hibernating segments is effective in reducing the risk of HEs while its role in improving VF or NYHA class is negligible.


Spinal Cord Injury During Attempted Cervical Interlaminar Epidural Injection of Steroids.
Interlaminar cervical epidural injections are commonly performed in the practice of interventional pain medicine. Injury to the spinal cord following injection into the substance of the cord is a known complication of this procedure, but it has rarely been reported and illustrated in the literature. To describe and analyze a case where an inadvertent injection of contrast medium into the cervical spinal cord occurred. Highlighted is the dissonance between how the procedure was performed and published guidelines for its performance. Presented is the first published oblique fluoroscopic image of an intramedullary injection. By recognizing the potential complications of a procedure, and by describing means of avoiding those complications, practice guidelines serve to reduce the risk, and thereby the incidence of complications. Deviation from established best practice guidelines reinstates risks of complications that can be avoided.


Physiology of cumulative defect curves; consequences in glaucoma perimetry.
Purely diffuse field loss is a controversial sign of early glaucoma. Cumulative defect curves have been proposed to distinguish between diffuse and localized visual field loss. In such curves, pointwise deviations from the normal reference field are ranked. The deviations are then compared with normative limits for each rank. The ranking leads to a complete loss of spatial information and ignoration of pointwise physiological threshold variability. We believed that this might impair the curves' intended ability to distinguish diffuse and localized types of defects. The lower 5% normative limit was estimated for each rank in the cumulative defect curve using Humphrey 30-2 tests of 88 subjects from the Statpac normal database. For each rank we identified those two test points (among the total of 6512 (74 test points in each of 88 subjects)) from which the 5% limit was calculated. The average eccentricity, eccrank, of those two points was then determined at each rank. For lower to intermediate ranks eccrank was spread out from center to periphery. When instead the 20 highest ranks (most depressed points) were considered eccrank was much concentrated peripherally. Our normative limits were subsequently used to evaluate field results in 101 patients with glaucoma. In this glaucoma evaluation group, the largest deviations were often encountered in central or paracentral scotomas, in sharp contrast to the more peripheral position in the normative group. These deviations often failed to reach the cumulative defect curve limits which originated from points in the mid-periphery where normal variability is large. At present, cumulative defect curves are not optimized to distinguish diffuse and localized field loss.


Prehemodialysis arteriovenous access creation is associated with better cardiovascular outcomes in patients receiving hemodialysis: a population-based cohort study.
Cardiovascular (CV) disease contributes to nearly half of the mortalities in patients with end-stage renal disease. Patients who received prehemodialysis arteriovenous access (pre-HD AVA) creation had divergent CV outcomes. We conducted a population-based cohort study by recruiting incident patients receiving HD from 2001 to 2012 from the Taiwan National Health Insurance Research Database. Patients' characteristics, comorbidities, and medicines were analyzed. The primary outcome of interest was major adverse cardiovascular events (MACEs), defined as hospitalization due to acute myocardial infarction, stroke, or congestive heart failure (CHF) occurring within the first year of HD. Secondary outcomes included MACE-related mortality and all-cause mortality in the same follow-up period. The patients in the pre-HD AVA group were younger, had a lower burden of underlying diseases, were more likely to use erythropoiesis-stimulating agents but less likely to use renin-angiotensin-aldosterone system blockers. The patients with pre-HD AVA creation had a marginally lower rate of MACEs but a significant 35% lower rate of CHF hospitalization than those without creation (adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) [0.48-0.88]). In addition, the pre-HD AVA group exhibited an insignificantly lower rate of MACE-related mortality but a significantly 52% lower rate of all-cause mortality than the non-pre-HD AVA group (adjusted HR 0.48, 95% CI [0.39-0.59]). Sensitivity analyses obtained consistent results. Pre-HD AVA creation is associated with a lower rate of CHF hospitalization and overall death in the first year of dialysis.


Unusual cause of thyroid abscess.
Thyroid abscess is a rare condition of the thyroid gland. The common causative organisms responsible for thyroid abscess are Staphylococci and Streptococci species. We described a case of thyroid abscess due to Klebsiella pneumoniae in an infant. The patient was successfully treated with open surgical drainage and appropriate antimicrobial agents.


Are multiple contrast tests superior to the ANOVA?
Multiple contrast tests can be used to test arbitrary linear hypotheses by providing local and global test decisions as well as simultaneous confidence intervals. The ANOVA-F-test on the contrary can be used to test the global null hypothesis of no treatment effect. Thus, multiple contrast tests provide more information than the analysis of variance (ANOVA) by offering which levels cause the significance. We compare the exact powers of the ANOVA-F-test and multiple contrast tests to reject the global null hypothesis. Hereby, we compute their least favorable configurations (LFCs). It turns out that both procedures have the same LFCs under certain conditions. Exact power investigations show that their powers are equal to detect their LFCs.


Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity.
The prostacyclin synthase gene isolated from human genomic libraries (PTGIS) consists of 10 exons spanning approximately 60 kb. All the splice donor and acceptor sites conform to the GT/AG rule. Genomic Southern blot and fluorescence in situ hybridization analyses revealed that the human prostacyclin synthase gene is present as a single copy per haploid genome and is localized on chromosome 20q13. 11-q13.13. The 1.5-kb sequence of the 5'-upstream of the translational initiation site contained both GC-rich and pyrimidine-rich regions and consensus sequences of the transcription factor recognition sites such as Sp1, AP-2, the interferon-gamma response element, GATA, NF-kappaB, the CACCC box, and the glucocorticoid response element. The core binding sequence (GAGACC) of the shear stress responsive element was also found in the 5'-flanking region of the gene. The major product of the primer extension analysis suggested that the transcription of the gene started from the positions around 49 bp upstream of the translational initiation codon. Transient transfection experiments using human aortic and bovine arterial endothelial cells demonstrated that the GC-rich region (positions -145 to -10) possessed a significant promoter activity. The 6-kb downstream sequence of the translational termination codon contained multiple polyadenylation signals, Alu repeat sequences, and the consensus sequence of the primate-repetitive DNA element, MER1. Two sizes of the prostacyclin synthase mRNAs (approximately 6 and 3.3 kb) were detected with the human aorta and lung. RNA blot hybridization analysis using the 3'-untranslated region as probe indicated that the sizes of the 3'-flanking regions were different in the major 6-kb and minor 3.3-kb mRNAs.


Local Tumor Staging of Breast Cancer: Digital Mammography versus Digital Mammography Plus Tomosynthesis.
Background Combined digital mammography (DM) and digital breast tomosynthesis (DBT) (hereafter, DM plus DBT) has increased cancer detection rates when compared with those achieved with DM-only screening. However, there is limited literature on DBT as an adjunct to mammography in the staging of known breast cancers. Purpose To compare the diagnostic accuracy of DM alone with that of DM plus DBT in the identification of additional ipsilateral and contralateral lesions in women with newly diagnosed breast cancer. Materials and Methods This prospective study ( https://clinicaltrials.gov , NCT01881880) included 166 women with breast cancer (mean age, 59.5 years ± 11; age range, 40-87 years) and used the aforementioned techniques, with breast MRI and pathologic verification of all suspected lesions as the reference standards. Four radiologists independently reviewed the DM and DM plus DBT images using the American College of Radiology Breast Imaging Reporting and Data Systems criteria for diagnosis of index lesions and presence of additional disease. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) obtained for DM and DM plus DBT were compared by using the McNemar test. Results Twenty-four women (14%) exhibited multifocal lesions; 20 (12%), multicentric lesions; 39 (23%), additional ipsilateral lesions; and 18 (11%), bilateral lesions. The sensitivities were higher for DM plus DBT than for DM in the diagnosis of multicentric (51% [41 of 80] vs 37% [30 of 80], P = .002) and additional ipsilateral (52% [81 of 156] vs 44% [69 of 156], P = .007) lesions. The AUC was larger for DM plus DBT than for DM (0.74 vs 0.67, P = .02) in the diagnosis of bilateral breast cancer. No significant differences in specificity were noted. The added diagnostic value of DBT was limited to the group of women with nondense breasts: For diagnosis of ipsilateral lesions, AUC of DM plus DBT versus DM was 0.74 versus 0.70 (P = .04). For diagnosis of contralateral lesions, AUC of DM plus DBT verus DM was 0.76 versus 0.68 (P = .02). Conclusion The combination of digital mammography with digital breast tomosynthesis improves diagnostic accuracy for additional ipsilateral and contralateral breast cancer in women with nondense breasts. © RSNA, 2019 See also the editorial by Moy in this issue.


Micro determinants of female migration in a developing country: labor market, demographic marriage market and economic marriage market incentives.
A micro study of inter-regional migration by women in Nicaragua is presented. The authors "explore three sets of migratory incentives: (1) labor market factors such as usually are emphasized; (2) 'demographic marriage market' considerations (i.e., the probability of having a male companion)...; and (3) 'economic marriage market' considerations (i.e., the expected earnings from a companion given regional labor market conditions and assortative mating)....[They] use estimates of expected outcomes in origin, destination and third regions--conditional upon the woman's characteristics and upon regional differences in labor and marriage markets--to explore the consistency of actual migratory flows with these three sets of migratory incentives." Data are from a sample of approximately 4,000 women aged 15-45 who were interviewed in 1977-1978.


Systematic review of the feasibility of laparoscopic reoperation for early postoperative complications following colorectal surgery.
Returning to the operating theatre for management of early postoperative complications after colorectal surgery is an important key performance indicator. Laparoscopic surgery has benefits that may be useful in surgical emergencies. This study explored the evidence for the advantages of laparoscopic reoperation. A systematic review was performed to identify publications reporting the outcomes of laparoscopy as a mode of reoperation for the management of early postoperative complications of colorectal surgery. The main outcomes examined were 30-day mortality, 30-day morbidity, length of hospital stay, second reoperation rate, ICU admission and stoma formation at reoperation. After screening 3657 citations, ten non-randomized cohort studies were identified (1137 reoperations). Laparoscopic reoperation was equivalent to or better than open reoperation, with lower rates of 30-day mortality (0-4·4 versus 0-13·6 per cent), 30-day morbidity (6-40 versus 30-80 per cent), length of stay (mean(s.d.) 15·8(2·8) versus 29·1(14·5) days), ICU admission and duration of stay in the ICU. Anastomotic leak was the most common indication, after which more patients received a defunctioning loop stoma instead of an end stoma at laparoscopic than open reoperation. Laparoscopic reoperation is feasible in selected patients, with the advantages of improved short-term outcomes.


Comparison of Prescribing Patterns Before and After Implementation of a National Policy to Reduce Inappropriate Alprazolam Prescribing in Australia.
Benzodiazepines have been a common target for policy interventions to curtail inappropriate use, with mixed results. To reduce alprazolam misuse, in February 2017, Australia delisted the 2-mg tablet strength from public subsidy, eliminated refills, and reduced the pack size from 50 tablets to 10 tablets. To describe changes in alprazolam dispensing, prescribing, and poisonings associated with the implementation of a new policy to reduce inappropriate prescription of alprazolam in Australia. This interrupted time series analysis and cross-sectional study included data from a 10% sample of Australian people who received publicly subsidized dispensing claims and prescribing approvals for alprazolam from January 1, 2015, to December 31, 2018, and all calls to a poison information service involving alprazolam from February 1, 2015, to October 31, 2018. Autoregressive error models were used to quantify changes over time and compare patterns of use before and after the intervention. Data analyses were conducted from November 2018 to May 2019. Implementation of the policy change on February 1, 2017. Monthly trends in alprazolam prescribing approvals and dispensings, quarterly trends in telephone calls involving alprazolam to a poison information service, and patterns of prescribing and dispensing before and after the intervention. From 2015 to 2018, there were 71 481 alprazolam dispensings to 6772 people. After the intervention, overall dispensing decreased by 51.2% (95% CI, 50.5%-51.9%) and prescribing approvals increased by 17.5% (95% CI, 13.0%-22.2%). Overall, the proportion of dispensing of packs of 51 to 100 tablets increased from 5776 of 24 282 dispensings (23.8%) to 4888 of 10 676 dispensings (45.8%) (risk difference [RD], 22.0% [95% CI, 19.4%-24.6%]) and dispensing of packs of more than 100 tablets increased from 1029 of 24 282 dispensings (4.2%) to 1774 of 10 676 dispensings (16.6%) (RD, 12.4% [95% CI, 10.6%-14.2%]). Among people receiving their first alprazolam prescription, initiation with packs of 10 tablets or fewer increased from 16 of 1127 people (1.4%) before the intervention to 139 of 589 people (23.6%) after the intervention (RD, 22.2% [95% CI, 18.7%-25.7%]). Alprazolam treatment initiation with packs of more than 50 tablets also increased from 63 of 1127 people (5.6%) before the intervention to 144 of 589 people (24.4%) after the intervention (RD, 18.9% [95% CI, 15.1%-22.6%]). During 1 year before the intervention, patients received a median (interquartile range [IQR]) total of 250 (50-600) tablets and median (IQR) total combined tablet strength of 188 (50-550) mg. During 1 year after the intervention, people were dispensed less alprazolam, with a median (IQR) total of 200 (50-500) tablets and median (IQR) total combined tablet strength of 120 (30-360) mg. There was little change in poisoning calls involving alprazolam. This study found that after the policy intervention, subsidized alprazolam use decreased, but the increase in prescribing approvals placed additional burden on prescribers. Even after the intervention, most people who were dispensed alprazolam were still receiving treatment contrary to best-practice recommendations. Furthermore, the poison information center data suggested that people were still being dispensed the 2-mg tablet strength, presumably as nonsubsidized (ie, private) prescriptions.


Polyhydroxy Ester Stabilized Perovskite for Low Noise and Large Linear Dynamic Range of Self-Powered Photodetectors.
Solution-processed perovskites as emerging semiconductors have achieved unprecedented milestones in sensor optoelectric devices. Stability along with the device noise issues are the major obstacle for photodetectors to compete with the traditional devices. Here, we demonstrated that l-ascorbic acid (l-AA) as a polyhydroxy ester can coordinate with the amino group of formamidine cations (FA+) through multiple hydrogen bond interactions to stabilize the perovskite, which protect the FA+ ions from nucleophile attack and effectively suppress the degradation of FA+ ions, improving the perovskite stability and suppressing the device noise to below 0.3 pA Hz-1/2 with a large linear dynamic range of 239 dB. The dual functions of l-AA enable the perovskite photodetector to have a high detectivity of 1012 Jones. The self-powered device works with no energy consumption and maintains an undegraded performance over 1200 h of inspection at ambient conditions, which is promising for infrastructure construction, signal sensing, and real-time information delivery.


Chronic CD30 signaling in B cells results in lymphomagenesis by driving the expansion of plasmablasts and B1 cells.
CD30 is expressed on a variety of B-cell lymphomas, such as Hodgkin lymphoma, primary effusion lymphoma, and a diffuse large B-cell lymphoma subgroup. In normal tissues, CD30 is expressed on some activated B and T lymphocytes. However, the physiological function of CD30 signaling and its contribution to the generation of CD30+ lymphomas are still poorly understood. To gain a better understanding of CD30 signaling in B cells, we studied the expression of CD30 in different murine B-cell populations. We show that B1 cells expressed higher levels of CD30 than B2 cells and that CD30 was upregulated in IRF4+ plasmablasts (PBs). Furthermore, we generated and analyzed mice expressing a constitutively active CD30 receptor in B lymphocytes. These mice displayed an increase in B1 cells in the peritoneal cavity (PerC) and secondary lymphoid organs as well as increased numbers of plasma cells (PCs). TI-2 immunization resulted in a further expansion of B1 cells and PCs. We provide evidence that the expanded B1 population in the spleen included a fraction of PBs. CD30 signals seemed to enhance PC differentiation by increasing activation of NF-κB and promoting higher levels of phosphorylated STAT3 and STAT6 and nuclear IRF4. In addition, chronic CD30 signaling led to B-cell lymphomagenesis in aged mice. These lymphomas were localized in the spleen and PerC and had a B1-like/plasmablastic phenotype. We conclude that our mouse model mirrors chronic B-cell activation with increased numbers of CD30+ lymphocytes and provides experimental proof that chronic CD30 signaling increases the risk of B-cell lymphomagenesis.


Greek fathers' experiences from their wife's/partner's labour and delivery: A qualitative approach.
This study aimed at exploring Greek fathers' experiences from their wives/partners' labour and delivery, and their perceptions about aspects of delivery care that need to be improved. It took place at hospital maternity clinics at the greater area of Thessaloniki, Greece. Participants were fathers whose wife/partner had given birth one week to one year before the data collection. The data were collected with the use of the Kuopio Instrument for Fathers (KIF). In this article we present the data obtained by KIF's four open-ended questions, which were analyzed using the method of content analysis. Three core categories emerged: (i) Meaning of presence during the delivery process; (ii) Experiences of the delivery process; and (iii) Suggestions for improving delivery services. Fathers take their role seriously and seek an active participation. Healthcare professionals and health education interventions should take into account the fathers' perspectives and aim to meet their needs.


[Quality grading of artificial tuber seed of Pinellia ternata].
To establish the seed quality grading standard of artificial tuber of Pinellia ternata. Hundred-grain weight, moisture content, germination rate, viability, single-grain diameter, purity and visual form of mature artificial tuber seed from tissue culture of P. ternate were determined. The key indicator and reference indicators for artificial tubers quality grading were defined statistically by SPSS analysis. Germination rate and viability were the primary indicators, hundred-grain weight, moisture content and purity were important reference indicators. The quality of each grade should reach the following requirements: for first grade, hundred-grain weight > 10 g, moisture content > 70%-80% , germination rate > 80%, viability > 85%, single-grain diameter > 0.7 cm, purity > 80%; for second grade, hundred-grain weight 8-10 g, moisture content > 70%-80%, germination rate 60%-80%, viability 70%-85%, single-grain diameter 0.3-0.7 cm, purity 75%-80%; moisture content > 70%-80%, and the others don't reach second grade was the third grade.


Homozygous deletions at 8p22 and 8p21 in prostate cancer implicate these regions as the sites for candidate tumor suppressor genes.
Frequent loss of an allele at specific chromosomal regions implicates these regions as sites of tumor suppressor genes (TSG) that become inactivated during tumor progression. We have studied chromosome 8p allele losses in 32 primary human prostate carcinomas with 16 polymorphic microsatellite sequences. Overall, 22 of 32 (69%) informative specimens showed loss of allele in at least one locus. The most frequent losses of heterozygosity (LOH) occurred at the LPL locus (46%) on chromosome 8p22 and at the D8S360 (45%) and NEFL (43%) loci on chromosome 8p21. Homozygous deletions were detected at the LPL and NEFL loci at 8p22 and 8p21, respectively. The minimal region with frequent LOH and homozygous deletion, around the LPL locus, was restricted between the MSR locus and the D8S258 marker, separated by less than 9 cM. The second region was restricted between markers D8S1128 and D8S131 separated by 12 cM. The results suggest the existence of two chromosome 8p sites for candidate TSGs in prostate cancer.


Analysis of affected sib pairs, with covariates--with and without constraints.
Covariate models have previously been developed as an extension to affected-sib-pair methods in which the covariate effects are jointly estimated with the degree of excess allele sharing. These models can estimate the differences in sib-pair allele sharing that are associated with measurable environment or genes. When there are no covariates, the pattern of identical-by-descent allele sharing in affected sib pairs is expected to fall within a small triangular region of the potential parameter space, under most genetic models. By restriction of the estimated allele sharing to this triangle, improved power is obtained in tests for genetic linkage. When the affected-sib-pair model is generalized to allow for covariates that affect allele sharing, however, new constraints and new methods for the application of constraints are required. Three generalized constraint methods are proposed and evaluated by use of simulated data. The results compare the power of the different methods, with and without covariates, for a single-gene model with age-dependent onset and for quantitative and qualitative gene-environment and gene-gene interaction models. Covariates can improve the power to detect linkage and can be particularly valuable when there are qualitative gene-environment interactions. In most situations, the best strategy is to assume that there is no dominance variance and to obtain constrained estimates for covariate models under this assumption.


[X-ray VTR analysis of esophagocardiac motion in cases of cervical dysphagia].
Using X-ray VTR motion analysis to diagnose a total of 103 cervical dysphagial cases, we obtained the following conclusions. Among these dysphagial cases, there were only 32 cases (31%) of clear organic or functional disease which we commonly considered to be the cause of dysphagia, and there were no less than 71 cases (69%) in which we could not identify the cause of the dysphagia. In 29 of these 71 cases, recording conditions of whole esophageal systole and diastole through the passage of contrast medium (Barium) were insufficient. We compared the remaining 42 cases with 42 normal cases, focussing on the lower esophagocardiac movement. In these dysphagial cases, angle of barium inflow tended to steepen statistically, and Barium discharge of the ampulla was tended towards incomplete discharge. In conclusion, this method is thought to contribute to the diagnosis of dysphagial cases except clear organic or functional diseases which we commonly consider to be the cause of the dysphagia.


Attachment, autonomy, intimacy: some clinical implications of attachment theory.
This paper reviews the origins and current state of attachment theory, especially as relevant to the practice of psychotherapy. It is suggested that attachment experience becomes internalized as self-narrative around the age 3-5, and that these self-narratives form the basis of reflexive self-function and autobiographical competence in later life, as revealed by the Adult Attachment Interview. It proposes that the fundamental aims of psychotherapy can be characterized as the search for intimacy and autonomy, arising on the basis of parental attunement and containment of healthy protest, of which analogues are to be found in adult psychotherapy. A 'triangle of attachment' is introduced at whose apices are attachment, detachment and 'non-attachment' respectively. Attachment, which arises out of a secure base, provides the starting point for intimacy; the capacity for healthy protest and therefore detachment is the basis of autonomy; from non-attachment comes the capacity to reflect on oneself and so to disidentify with painful or traumatic experience.


Immunosenescence: the role of age in multiple sclerosis.
The number of elderly people with multiple sclerosis (MS) has increased in line with population ageing. As the immune system presents profound changes over an individual's lifetime, it is important to understand the differences between these patients and younger patients. Immunosenescence, defined as age-related alterations naturally occurring in the immune system, particularly influences tolerance, response, and adverse effects of disease-modifying treatments for MS. Thymic involution is the most noteworthy characteristic of this phenomenon. This process leads to a reduction in the number of virgin T cells. Other effects include an inverted CD4+/CD8+ cell ratio, severe alterations in NK cell functioning, and reduced tissue repair capacity in the brain. The number of older people with MS is increasing due to population ageing, advances in disease-modifying treatments, and improved health and social care of these patients. Ageing of the immune system increases the risk of infections, tumours, and autoimmune diseases in elderly individuals. Furthermore, neurodegeneration is accelerated in patients with MS due to the nervous system's loss of remyelination capacity. Understanding of the changes affecting the immune system in the elderly population is essential to improving the care provided to this ever-growing patient group.