Dust Rains Deliver Diverse Assemblages of Microorganisms to the Eastern Mediterranean.
Dust rains may be particularly effective at delivering microorganisms, yet their biodiversities have been seldom examined. During 2011 and 2012 in Beirut, Lebanon, 16 of 21 collected rainfalls appeared dusty. Trajectory modelling of air mass origins was consistent with North African sources and at least one Southwest Asian source. As much as ~4 g particulate matter, ~20 μg DNA, and 50 million colony forming units were found deposited per square meter during rainfalls each lasting less than one day. Sequencing of 93 bacteria and 25 fungi cultured from rain samples revealed diverse bacterial phyla, both Gram positive and negative, and Ascomycota fungi. Denaturing Gradient Gel Electrophoresis of amplified 16S rDNA of 13 rains revealed distinct and diverse assemblages of bacteria. Dust rain 16S libraries yielded 131 sequences matching, in decreasing order of abundance, Betaproteobacteria, Alphaproteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Cyanobacteria, Epsilonproteobacteria, Gammaproteobacteria, and Deltaproteobacteria. Clean rain 16S libraries yielded 33 sequences matching only Betaproteobacteria family Oxalobacteraceae. Microbial composition varied between dust rains, and more diverse and different microbes were found in dust rains than clean rains. These results show that dust rains deliver diverse communities of microorganisms that may be complex products of revived desert soil species and fertilized cloud species.


In the company of my sisters: sister circles as an anxiety intervention for professional African American women.
Sister circles have been used within African American communities to raise awareness about physical health. The possibility exists that sister circles could be used to educate and teach women strategies about managing anxiety and panic. In this paper we examine professional Black women's conceptualization of panic attacks and other related anxiety issues. Then, we explore the feasibility of sister circles as a psycho-educational anxiety intervention for African American professional women. Four focus groups (n=37) were conducted. Focus group interviews were transcribed and were coded into three categories: (a) a major theme; (b) a minor theme; or (c) an off-topic comment. Specifically, we generate information regarding the key content and research components of a sister circle for African American female professionals. Focus group members saw a distinct difference between anxiety and panic. The number of African American women who experienced was seen as low. Women felt sister circles were a nice vehicle for helping African American women manage their anxiety and panic. Confidentially was a key component. Sister circles for anxiety and panic were seen as a natural outgrowth of African American women's professional networks. Limited data were collected on participant's anxiety levels. Overall, sister circles were seen as feasible interventions for African American professional women. The data from the focus groups were used to enhance the development of a sister circle intervention for anxious professional African American women.


Applications of nuclear medicine in ophthalmology.
Diagnostic techniques using radioactive isotopes can be used for the investigation of cerebral, orbital and intraocular tumours and for the dynamic study of tear flow. The value of such techniques in the study of obstruction of the nasolacrymal system (particularly partial and functional obstructions) has been established and the possibility of using Tc99m clearance for the investigation of dry eyes is being investigated.


Effect of suboptimal breast-feeding on occurrence of autism: a case-control study.
To evaluate the association between suboptimal breast-feeding practices and autism spectrum disorders (ASDs). A case-control study was conducted in 102 ASD cases and 102 matched healthy controls. Based on adjusted odds ratios from logistic regression models, ASD was found to be associated with the late initiation of breast-feeding (odds ratio 1.48, 95% confidence interval 1.01-3.1), a non-intake of colostrum (odds ratio 1.7, 95% confidence interval 1.03-4.3), prelacteal feeding, and bottle-feeding. The risk of ASD was found to decrease in a dose-response fashion over increasing periods of exclusive breast-feeding (P for trend = 0.04) and continued breast-feeding (P for trend = 0.001). The study indicates that increased ASD risk is generally associated with suboptimal breast-feeding practices.


Isoproterenol reversal of antiarrhythmic effects in patients with inducible sustained ventricular tachyarrhythmias.
Seventeen patients (16 men and 1 woman) were challenged with isoproterenol after their initially inducible sustained ventricular tachyarrhythmia (monomorphic tachycardia in 14 patients and fibrillation in 3) was completely suppressed by class I antiarrhythmic drugs. Coronary artery disease was documented in 11 patients, dilated cardiomyopathy in 2 and no structural heart disease in the remaining 4 patients. The initial presentation was aborted sudden cardiac death (five patients), syncope (eight patients) and symptomatic nonsustained ventricular tachycardia (four patients). The antiarrhythmic drug that rendered the initial ventricular tachyarrhythmias noninducible was class IA in 11 cases, class IC in 5 and combined class IA and IB in 1. The original ventricular tachyarrhythmia became reinducible in 10 patients (group A) and remained noninducible in 7 patients (group B) after isoproterenol infusion at a rate necessary to achieve a 20% increase in heart rate. Despite the results of isoproterenol challenge, all patients were maintained on their electrophysiologically guided antiarrhythmic regimen. During a mean follow-up period of 13 +/- 9 months, 3 of the 10 patients in group A experienced clinical recurrence of tachyarrhythmia; no recurrence was noted in group B. In conclusion, reinducibility of ventricular tachyarrhythmia after beta-adrenergic stimulation seems to identify a subgroup of patients at high risk of subsequent arrhythmic events. Beta-adrenergic blockade or surgical therapy may be indicated in some patients with a positive isoproterenol challenge.


Mental health in Kashmir: conflict to COVID-19.
Owing to the enduring conflict in Kashmir, there has been an increase in psychological problems. On top of that, the COVID-19 pandemic has added an additional burden on the mental health system of Kashmir. There is an unmet and immediate need to escalate the mental health services in Kashmir consisted of community participation, awareness programs, and mental health rehabilitation services.


CB2 receptor in the CNS: From immune and neuronal modulation to behavior.
Despite low levels of cannabinoid receptor type 2 (CB2R) expression in the central nervous system in human and rodents, a growing body of evidence shows CB2R involvement in many processes at the behavioral level, through both immune and neuronal modulations. Recent in vitro and in vivo evidence have highlighted the complex role of CB2R under physiological and inflammatory conditions. Under neuroinflammatory states, its activation seems to protect the brain and its functions, making it a promising target in a wide range of neurological disorders. Here, we provide a complete and updated overview of CB2R function in the central nervous system of rodents, spanning from modulation of immune function in microglia but also in other cell types, to behavior and neuronal activity, in both physiological and neuroinflammatory contexts.


Dreams, katharsis and anxiety.
Over the centuries, the importance and the nature of the relationship of "inside" and "outside" in human experience have shifted, with consequences for notions of mind and body. This paper begins with dreams and healing in the Asklepian tradition. It continues with Aristotle's notions of psuche and how these influenced his conception of katharsis and tragedy. Jumping then to the 17th century, we will consider Descartes' focus on dreams in his theories of thinking. Finally, we will turn explicitly to Freud's use of dreams in relation to his theories of anxiety, of psychic processes and of the Oedipus Complex.


Adult hemophagocytic lymphohistiocytosis with severe pulmonary hypertension and a novel perforin gene mutation.
Adult hemophagocytic lymphohistiocytosis (HLH) is a rare and deadly hyperinflammatory syndrome presenting both diagnostic and therapeutic challenges. HLH may be primary, due to an underlying genetic abnormality, and/or secondary to infection, malignancy, or rheumatologic conditions. We describe a case of HLH-associated severe pulmonary hypertension paralleling Epstein-Barr virus (EBV) reactivation in a 52-year-old male in whom a novel perforin missense mutation was found (PRF1 1517C>T). Although intolerant of standard therapy (HLH-2004 protocol), a 6-week course of anti-CD52 (alemtuzumab) was associated with freedom-from-transfusion from weeks 4 to 13. However, 15 weeks after the onset of salvage therapy, he succumbed to polymicrobial sepsis despite treatment with prophylactic anti-infectives, with necropsy revealing disseminated blastomycosis and relapsed HLH. This case illustrates uncertainties in the relationships between pulmonary hypertension, a newly described PRF1 mutation, and possible pre-existing latent infectious risk factors (such as EBV or Blastomyces) in the pathogenesis and therapeutic perils of adult HLH.


Patient response to osteotomy around the knee joint at one year post-operation-fulfilment of expectations and current health status.
The aim of this study was to investigate patient satisfaction and fulfilment of expectations after osteotomy around the knee at one year postoperatively, using patient-related outcome measures. From the initial sample of 264 patients, a total of 132 patients (age 48y ± 11) were enrolled in this prospective study (response rate 49.3%). Data were collected using the Hospital For Special Surgery-Knee Surgery Expectations Survey (HFSS-KSES), items for satisfaction and the Knee injury and Osteoarthritis Outcome Score (KOOS) measures. At one year postoperative follow-up, an individualized questionnaire asked whether the specific person-related expectations had been fulfilled. Satisfaction was high with 83.2% of all participants at one year after surgery. A total of 78% of patients stated they would decide to do the surgery again. This decision was significantly associated with satisfaction, younger age and better KOOS scores scales before surgery for pain, activity and sports. We found high correlations between satisfaction and fulfilment of expectations for the HFES-KSES. Fulfilment of expectations one year after surgery was significantly associated with significant improvements in KOOS scales at one year post-operation. Expectations (1) "to get the knee back to normal status", (2) "improve ability to squat", (3) "improve ability to run", (4) "improve ability to kneel" had been fulfilled worst. A multiple linear regression model for satisfaction had an R2 = 0.797 of the variance. The most influential was the variable fulfilment of "maintain health" that had 70.7% of variance. The fulfilled expectation concerning an improvement of the ability to maintain health was the most influential parameter for satisfaction at one year post-osteotomy. Patients with better health status of the knee and younger age rated the surgery to be more positive and were also more likely to do the surgery again. This provides an indication for an earlier intervention, before the knee and overall health status becomes more detrimental. Level II (Therapeutic study).


Design Principles of Perovskites for Thermochemical Oxygen Separation.
Separation and concentration of O2 from gas mixtures is central to several sustainable energy technologies, such as solar-driven synthesis of liquid hydrocarbon fuels from CO2 , H2 O, and concentrated sunlight. We introduce a rationale for designing metal oxide redox materials for oxygen separation through "thermochemical pumping" of O2 against a pO2 gradient with low-grade process heat. Electronic structure calculations show that the activity of O vacancies in metal oxides pinpoints the ideal oxygen exchange capacity of perovskites. Thermogravimetric analysis and high-temperature X-ray diffraction for SrCoO3-δ , BaCoO3-δ and BaMnO3-δ perovskites and Ag2 O and Cu2 O references confirm the predicted performance of SrCoO3-δ , which surpasses the performance of state-of-the-art Cu2 O at these conditions with an oxygen exchange capacity of 44 mmol O 2 mol SrCoO 3-δ(-1) exchanged at 12.1 μmol O 2 min(-1) g(-1) at 600-900 K. The redox trends are understood due to lattice expansion and electronic charge transfer.


Management of fever in infants and children.
There is no question that fever is a source of great consternation for parent and physician alike; however, it is impossible to predict with certainty the outcome of every febrile illness. Inherent in the words diagnostic impression is a degree of uncertainty. The only question remaining is how much uncertainty is in the best interest of the child. Physicians try to use the existing scientific data to best determine the prevalence of disease and outcome. At the same time, they must recognize the limitations of both the data and their ability to be generalized to every population. Everything clinicians do has risks and costs, which they must balance against the incidence of complications and the benefits of testing. To take away clinical judgment makes physicians technicians not clinicians.


Psychological aspects of atrial fibrillation: A systematic narrative review : Impact on incidence, cognition, prognosis, and symptom perception.
Atrial fibrillation (AF) is the most frequent arrhythmia in the general population. This review aims to provide a comprehensive overview of the psychological aspects of AF, compiling evidence from epidemiological, clinical, and basic research sources. Findings from large-scale population-based and clinical longitudinal studies reveal an association between negative affectivity (e.g. depression) and the incidence and clinical prognosis of AF. Studies investigating the impact of work stress parameters on AF onset show conflicting results. Researchers have reported the impact of AF on cognitive decline and on health-related quality of life, and have highlighted the role of interoceptive cues in the development of AF symptom burden and gender differences in psychological covariates of AF. Among biological pathways linking psychosocial factors to AF, research on autonomic regulation has yielded the most evidence so far, showing that the onset of AF is associated with simultaneous sympatho-vagal activation rather than an increase in vagal or sympathetic drive alone. Thus, modulation of the autonomic nervous system is likely to be a promising strategy for protecting the myocardium from pro-arrhythmic autonomic influences. In total, the findings show that AF is embedded as a disease condition in a psycho-societal context and is not an isolated medical problem per se. A broader perspective than a focus on the electrophysiology alone is urgently needed.


Pain Syndromes Secondary to Cluneal Nerve Entrapment.
The purpose of this review is to provide an overview of the cluneal nerves, present a summary of pain syndromes secondary to clunealgia, and evaluate current literature for diagnostic and treatment modalities. Multiple trials and studies have reported success with numerous modalities ranging from nerve blocks, neuroablation, and even peripheral neuromodulation with varying degrees of clinical benefit. Cluneal nerve entrapment or chronic impingement can cause buttock pain or referred pain to nearby areas including the lower back, pelvic area, or even the lower extremities. Clunealgias and associated pain syndromes can often be challenging to diagnose and differentiate. An appreciation of the pathophysiology of clunealgias can assist with patient selection for interventional pain strategies targeted towards the cluneal nerves, including nerve blocks, neuroablation, and peripheral neuromodulation. More research is needed to better delineate the efficacy of these procedures for clunealgias.


Giardia lamblia: localization of hydrolase activities in lysosome-like organelles of trophozoites.
Homogenates of Giardia lamblia trophozoites exhibited the following hydrolase activities: acid phosphatase (EC 184.108.40.206), proteinase (EC 3.1.4) with urea-denatured hemoglobin and N-benzoyl-DL-arginine-2-naphthylamide as substrates, deoxyribonuclease (EC 184.108.40.206), and ribonuclease (EC 22.214.171.124). beta-N-Acetylglucosaminidase (EC 184.108.40.206), beta-galactosidase (EC 184.108.40.206), beta-glucuronidase (EC 126.96.36.199), alpha-D-glucosidase (EC 22.214.171.124), beta-D-glucosidase (EC 18.104.22.168), and beta-D-xylosidase (EC 220.127.116.11) activities were below the level of detection. Differential and isopycnic centrifugation of homogenates demonstrated that giardial hydrolases were localized in a single-particle population sedimenting at 7200g for 30 min. The particles had a buoyant density in sucrose of 1.15 and exhibited latency. Latency was completely destroyed by Triton X-100 or 15 cycles of freezing and thawing. After centrifugation of Triton- or freeze-thaw-treated particle fractions, the hydrolase activities, though no longer latent, were still sedimentable suggesting tight binding to the organelle membrane. Latency was destroyed simultaneously for all hydrolases, in direct proportion to the amount of Triton added to a particle preparation or to the number of times a particle preparation was subjected to freezing and thawing. These results support the suggestion that the hydrolases of G. lamblia trophozoites are localized in a single-particle population of lysosome-like organelles.


Programmed Death Ligand 1 Is Overexpressed in Liver Macrophages in Chronic Liver Diseases, and Its Blockade Improves the Antibacterial Activity Against Infections.
Bacterial infections are common and severe in cirrhosis, but their pathogenesis is poorly understood. Dysfunction of liver macrophages may play a role, but information about their function in cirrhosis is limited. Our aims were to investigate the specific profile and function of liver macrophages in cirrhosis and their contribution to infections. Macrophages from human cirrhotic livers were characterized phenotypically by transcriptome analysis and flow cytometry; function was assessed in vivo by single photon emission computerized tomography in patients with cirrhosis. Serum levels of specific proteins and expression in peripheral monocytes were determined by ELISA and flow cytometry. In vivo phagocytic activity of liver macrophages was measured by spinning disk intravital microscopy in a mouse model of chronic liver injury. Liver macrophages from patients with cirrhosis overexpressed proteins related to immune exhaustion, such as programmed death ligand 1 (PD-L1), macrophage receptor with collagenous structure (MARCO), and CD163. In vivo phagocytic activity of liver macrophages in patients with cirrhosis was markedly impaired. Monocytes from patients with cirrhosis showed overexpression of PD-L1 that paralleled disease severity, correlated with its serum levels, and was associated with increased risk of infections. Blockade of PD-L1 with anti-PD-L1 antibody caused a shift in macrophage phenotype toward a less immunosuppressive profile, restored liver macrophage in vivo phagocytic activity, and reduced bacterial dissemination. Liver cirrhosis is characterized by a remarkable impairment of phagocytic function of macrophages associated with an immunosuppressive transcriptome profile. The programmed cell death receptor 1/PD-L1 axis plays a major role in the impaired activity of liver macrophages. PD-L1 blockade reverses the immune suppressive profile and increases antimicrobial activity of liver macrophages in cirrhosis.


Genetic analysis of tumorigenesis: XVI. Chromosome changes in azacytidine- and insulin-induced tumorigenesis.
Chromosome changes accompanying differentiation and tumorigenesis in azacytidine- (azaC) and insulin-induced preadipocytes of the Chinese hamster embryo fibroblast cell line CHEF/18 are described. Karyotype analysis of 47 clones, subclones, and tumor-derived cells has shown that trisomy for chromosome 3q (mar 1) is characteristic of azaC preadipocytes but not of insulin preadipocytes. AzaC preadipocytes were consistently tumorigenic as well as trisomic for chromosome 3q, whereas most insulin preadipocytes were nontumorigenic and diploid. Only the few insulin preadipocytes that were tumorigenic were also trisomic for chromosome 3q. Among the tumor-derived cell lines recovered from azaC preadipocytes injected into nude mice, four had no additional chromosome changes except trisomy for 3q, as detected by karyotype analysis. Thus trisomy for 3q may be a sufficient chromosome change to induce tumor-forming ability in these cells. The rearrangements of chromosome 3 seen in this and other work pinpoint the trisomic region between the centromere and 3q5.


EGLP-1 lowers body weight better than exendin-4 by reducing food intake and increasing basal energy expenditure in diet-induced obese mice.
It is well known that GLP-1 activates GLP-1R to reduce body weight by inhibiting eating. GLP-1 is cleaved by the neutral endopeptidase (NEP) 24.11 into a pentapeptide GLP-1 (32-36) amide, which increases basal energy expenditure and inhibits weight gain in obese mice. It is well known that GLP-1 analogs can reduce weight by suppressing eating. However, there are few reports of reducing weight through the dual effects of inhibiting eating and increasing basic energy. Here, we report the peptide EGLP-1, a GLP-1 analogue, which can reduce food intake and increase basal energy expenditure. In C2C12 myotubes, EGLP-1 can increase both phosphorylation of acetyl CoA carboxylase (ACC) and the ratio between phosphorylation of ACC and the total expression of ACC (pACC/ACC). In diet-induced obese mice, EGLP-1 is more effective than exendin-4 in reducing body weight, reducing fat mass and improving hepatic steatosis. At the same time, EGLP-1 can improve hyperglycemia, reduce food intake, and improve insulin resistance, just like exendin-4. In addition, EGLP-1, not exendin-4, can improve physiological parameters associated with lipid metabolism and increase oxygen consumption by increasing uncoupling proteins 3 (UCP3) expression and pACC/ACC ratio in skeletal muscle. Taken together, this data showed that EGLP-1 is able to reduce body weight by reducing food intake and increasing basal energy expenditure, suggesting it may be more effective in treating diabetic and non-diabetic overweight or obese people than pure GLP-1R agonist exendin-4.


Studies on secretory glycoproteins in the rat exocrine pancreas. III. Intracellular transport of fucose-labeled proteins as studied by cell fractionation.
The transcellular movement of fucosylated glycoproteins has been studied in vitro using rat pancreatic lobules and cell fractionation procedures, and has been compared with the well established pathway of secretory proteins. Using tritiated leucine as pulse label for the latter, their translocation from the rough endoplasmatic reticulum into the Golgi complex and finally into zymogen granules could be followed. In the case of glycoproteins, 14C-fucose was incorporated mainly into the smooth microsomal fraction (representative of the Golgi complex) and only one third of this specific activity was transported into the zymogen granule fraction. A detailed analysis of this fraction after separation of the content of zymogen granules from their membranes revealed a predominant labeling of membrane glycoproteins by 14C-fucose. In comparison, leucine-labeled bulk proteins were found almost exclusively in the zymogen granule content fraction, with little radioactivity in the membrane fraction. The data indicate a concomitant synthesis of fucosylated glycoproteins destined in part for the zymogen granule membrane and to a greater amount associated with the smooth microsomal fraction. The results are discussed in the light of recent findings indicating that about 40% of the proteins in the zymogen granule membrane are made up of one major glycoprotein which could be involved in the mechanism of exocytosis.


A rapid method for the preparation of the neutrophil fraction of granulocytes from human blood by centrifugation on isotonic Nycodenz gradients.
A rapid method for the preparation of neutrophils of the granulocyte fraction of human blood is described. A leucocyte-rich fraction is loaded onto preformed isotonic Nycodenz gradients, formed by mixing a stock isotonic Nycodenz solution with a NaCl diluent solution. After low speed centrifugation a neutrophil fraction of high viability, yield and purity can be isolated from the gradients.


Evaluation of the gastrointestinal tract in the child: CT, MRI, and isotopic studies.
The gastrointestinal radiologist no longer has to rely on indirect signs of extraluminal and solid organ pathology. With the use of the newer imaging modalities, including computed tomography, magnetic resonance imaging, and isotopic techniques, the entire abdomen and its contents can be directly visualized. Pathology, its extent and its effect on adjacent structures, can be readily appreciated.


Controlling feeding practices moderate the relationship between emotionality and food fussiness in young children.
Emotional child temperament has consistently been found to be related to food fussiness. One factor that may exacerbate or reduce the risk conferred by children's emotionality is parent feeding practices during mealtimes. Specifically, the use of controlling feeding practices aimed at increasing food consumption may particularly affect children with an emotional temperament. The primary aim of this study was to investigate whether the association between child food fussiness and higher emotionality found in previous studies is moderated by maternal use of controlling feeding practices, namely verbal pressure, physical prompts and food rewards. Sixty-seven mother-child dyads were video-recorded during a meal in their home and mothers' use of controlling feeding practices during this meal were coded. Mothers completed a questionnaire assessing child temperament. Moderation analyses revealed that maternal use of verbal pressure and physical prompts moderated the relationship between higher emotionality and food fussiness, but maternal use of food rewards did not. These results indicate that the use of verbal pressure and physical prompts may have a particularly negative influence on fussy eating for children higher in emotionality.


Glucose tolerance and insulin receptor binding to monocytes and erythrocytes in patients with cystic fibrosis.
Cystic fibrosis (CF) is the most frequent life threatening hereditary disease in the Western World with an incidence of approximately 1:2000. Due to increasing survival rates the high frequency of abnormal glucose tolerance has become an important problem. We compared insulin concentrations during oral glucose tolerance test and insulin receptor binding to both monocytes and erythrocytes from 9 patients with CF, with results from 10 healthy controls of similar body weight. The insulin: glucose ratio was increased in the fasting state (p less than 0.05) in patients with CF compared to controls, indicating an increased insulin resistance in CF-patients. The total insulin secretion during oral glucose tolerance test as judged by the area beneath the insulin curve was similar in the two groups, but insulin secretion was significantly delayed in patients with CF. Insulin receptor binding to monocytes and the number of receptors were significantly increased (p less than 0.01 and 0.02, respectively) in patients with CF whereas the dissociation constant was similar in patients with CF and controls. No difference was observed in insulin receptor binding to erythrocytes between the two groups. No correlations were found between insulin receptor binding to monocytes or erythrocytes and glucose tolerance or insulin concentrations.


Generic method for systematic phase selection and method development of biochromatographic processes. Part I. Selection of a suitable cation-exchanger for the purification of a pharmaceutical protein.
Even if the first protein therapeutics are now for more than 20 years on the market the selection of suitable adsorbents for the preparative downstream processing (DSP) of these biomolecules as well as the method development towards process conditions are still based mainly on 'trial and error'. Therefore, theses processes are not perfectly efficient, but indeed very time consuming and laborious. In this study a novel systematic method is introduced to find a suitable adsorbent (not necessarily the best one) with appropriate separation parameters for a specific separation with reduced effort. Following this strategy, the adsorbents must first be packed into columns under preparative conditions and then characterized completely with regard to, e.g. pressure drop, k'-values, plate heights (HETP curves), selectivity and capacity by using test substances, which are similar in their characteristics (molecular mass, size, charge distribution, hydrophobicity) to the target proteins. With the database once determined, a preselection of most suitable adsorbents including separation parameters is made regarding chromatographic and also economical properties. After this, preparative experiments must be conducted with a reduced number of adsorbents to figure out the individual influence of side components. This approach is demonstrated for the separation of an exemplary industrial protein mixture using cation-exchange chromatography (CEX). Characterization of different weak CEX-adsorbents is illustrated. After comparing these phases with each other, a first preselection and a prediction of suitable adsorbents is made. In the following preparative separation conditions (load, velocity, gradient) are determined for the preparative separations using the database and results of some additional experiments. The final comparison of separation performance in preparative scale confirms this selection and so the applicability of the new method.


Apoptosis in amyotrophic lateral sclerosis--what is the evidence?
There is increasing evidence that a programmed mechanism of cell death resembling apoptosis is responsible for motor-neuron degeneration in amyotrophic lateral sclerosis. Our understanding of the cell-death pathway has come from studies of both experimental models and human tissue. Here we examine in detail the in vitro and in vivo evidence for and against apoptosis in amyotrophic lateral sclerosis, looking at morphological changes, caspase activation, alterations in Bcl-2 oncoproteins, involvement of death receptors, expression of apoptosis-related molecules, and the role of the p53 pathway. Finally, we present evidence of potential therapeutic agents that could modulate the apoptotic pathway in amyotrophic lateral sclerosis and slow disease progression.


Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha beta-subunit junction region of prohaptoglobin.
The biosynthesis of rat haptoglobin, a hetrotetrameric glycoprotein (alpha 2 beta 2), requires the post-translational cleavage of its glycosylated primary translation product (prohaptoglobin) into alpha- and beta-subunits (Hanley, J. M., Haugen, T. H., and Heath, E. C. (1983) J. Biol. Chem. 258, 7858-7869). To elucidate the site(s) at which proteolytic cleavage occurs in prohaptoglobin, we have isolated a recombinant plasmid whose cDNA insert encodes for the carboxyl terminus of the alpha-subunit, the alpha beta-subunit junction, and the beta-subunit region, and also the entire 3'-untranslated region (142 base pairs) and poly(A) tail (55 base pairs) of the mRNA. A single arginine residue was found at the alpha beta-subunit junction region -Val-Gln-Arg-Ile-Ile-Gly-Gly-of prohaptoglobin. The sequence homology of this region with serine protease precursors suggests that post-translational processing of prohaptoglobin involves cleavage of the Arg-Ile bond and extraction of the Arg residue. The rat beta-subunit shows a high degree (approximately 80%) of sequence homology with its human counterpart although it possesses only two of the four N-glycosylation sites present in human haptoglobin beta-subunit.


Bioluminescent evaluation of the therapeutic effects of total body irradiation in a murine hematological malignancy model.
We investigated the utility of in vivo bioluminescence imaging (BLI) in assessing the therapeutic effects of total body irradiation (TBI) in a murine hematological malignancy model. The suspension of Ba/F3 cells transduced with firefly luciferase and p190 BCR-ABL genes was exposed to ionizing radiation, and viable cell numbers and bioluminescent signals were measured serially. Mice intravenously inoculated with the cells underwent TBI at various doses. In vivo BLI was performed repeatedly until spontaneous death, and whole-body bioluminescence signals were determined as an indicator of whole-body tumor burden. In the cell culture study, bioluminescence signals generally reflected viable cell numbers, despite some overestimation immediately after irradiation. Sublethal TBI in mice transiently depressed the increase in whole-body signals and prolonged survival. Spontaneous death occurred at similar signal levels regardless of radiation dose. A significant negative correlation was found between survival and whole-body signal early after TBI. Significant dose dependence was demonstrated for both survival and signal increase early after TBI and was more evident for signal increase. Lethally irradiated mice without bone marrow transplantation died while showing weak signals. In mice receiving lethal TBI and syngeneic bone marrow transplantation, signal reduction and prolongation of survival were prominent, and whole-body signals at death were similar to those in nonirradiated or sublethally irradiated mice. In vivo BLI allows longitudinal, quantitative evaluation of the response to TBI in mice of a hematological malignancy model. Antitumor effects can be assessed early and reliably using in vivo BLI.


Granulocyte function in visceral leishmaniasis.
Nitroblue tetrazolium test in nine children with visceral leishmaniasis (VL) showed no increase of spontaneous reduction by neutrophils. The normal bactericidal activity of four of these patients excludes an impaired function of the neutrophils in VL.


High pressure NMR study of a small protein, gurmarin.
The effect of pressure on the structure of gurmarin, a globular, 35-residue protein from Gymnema sylvestre, was studied in aqueous environment (95% 1H2O/5% 2H2O, pH 2.0) with an on-line variable pressure NMR system operating at 750 MHz. Two-dimensional TOCSY and NOESY spectra were measured as functions of pressure between 1 and 2000 bar at 40 degrees C. Practically all the proton signals of gurmarin underwent some shifts with pressure, showing that the entire protein structure responds to, and is altered by, pressure. Most amide protons showed different degrees of low field shifts with pressure, namely 0-0.2 ppm with an average of 0.051 ppm at 2000 bar, showing that they are involved in hydrogen bonding and that these hydrogen bonds are shortened by pressure by different degrees. The tendency was also confirmed that the chemical shifts of the amide protons exposed to the solvent (water) are more sensitive to pressure than those internally hydrogen bonded with carbonyls. The pressure-induced shifts of the H alpha signals of the residues in the beta-sheet showed a negative correlation with the 'folding' shifts (difference between the shift at 1 bar and that of a random coil), suggesting that the main-chain torsion angles of the beta-sheet are slightly altered by pressure. Significant pressure-induced shifts were also observed for the side-chain protons (but no larger than 10% of the 'folding' shifts), demonstrating that the tertiary structure of gurmarin is also affected by pressure. Finally, the linearity of the pressure-induced shifts suggest that the compressibility of gurmarin is invariant in the pressure range between 1 and 2000 bar.


Differing degrees of susceptibility to experimental allergic encephalomyelitis among inbred strains of hamsters.
Susceptibility to experimental allergic encephalomyelitis was examined in five highly inbred strains of hamsters. The frequency of disease was reproducible within a given strain, but differed remarkably from strain to strain. Two strains--Bio 15.16 and Bio 87.20--appeared to share similar major histocompatibility genes. Despite genetic similarities, susceptibility to acute paralytic EAE was remarkably different in the two strains. Strain 15.16 hamsters consistently developed acute paralysis 10-21 days after sensitization with heterologous nervous tissue and immunologic adjuvants. Strain 87.20 hamsters never developed disease acutely. Protection from EAE was not absolute, however, for some animals developed histopathologic evidence of EAE. Using alternative methods to induce EAE did not alter susceptibility in 87.20 hamsters. Genetic analysis of offspring of susceptible 15.16 and resistant 87.20 hamsters suggested that a single autosomal gene, unrelated to the major histocompatibility locus, accounted for differences in EAE susceptibility in these two strains. This gene had a more profound influence on clinical patterns of EAE than on histopathologic markers of disease.


Relationship between Force-Velocity Profiles and 1,500-m Ergometer Performance in Young Rowers.
Rowing races require developing high level of force and power output at high contraction velocity. This study determined the force-velocity and power-velocity (F-P-V) profiles of lower and upper limbs of adolescent rowers and their relationships with a 1,500-m rowing ergometer performance. The power developed during the 1,500-m (P1500) was evaluated in fourteen national-level male rowers (age: 15.3±0.6 yrs). F-P-V profiles were assessed during bench pull (BP) and squat jump (SJ) exercises. The theoretical maximal values of force (F0), velocity (V0), power output (Pmax) and the F-V relationship slope (S FV ) were determined. The body mass (BM) influence on these relationships was considered using an allometric approach. F0 was 720±144 and 2146±405 N, V0 was 1.8±0.1 and 1.8±0.3 m·s-1, Pmax was 333±83 and 968±204 W and SFV was -391±54 and -1,200±260 N·s·m-1 for BP and SJ, respectively. Upper and lower limb F0 and Pmax were significantly related. P1500 was significantly (P<0.05) correlated to V0-BP, F0-BP, SFV-BP, Pmax-BP, F0-SJ and Pmax-SJ (r²=0.29 to 0.79). BM accounted for more than 90% of these relationships. Rowers' F-P-V profiles reflect adaptations to chronic rowing practice. F-P-V profiles and rowing performance correlations suggest that BP and SJ exercises are relevant to evaluate young rowers' explosive abilities.


Sialyllactose-binding modified DNA aptamer bearing additional functionality by SELEX.
We produced a novel cationic-charged modified DNA aptamer for sialyllactose that is a ubiquitous component of the cell surface responsible for the infection of several viruses by using the magnetic-particle-based SELEX method. After 13 rounds of selection we selected 22 clones as sialyllactose-binding DNA aptamers composed of several modified thymidines. The DNA aptamers could form a three-way junction structure that likely forms a binding site for siallyllactose. The three-way junction structure contains several modified thymidines bearing a positively-charged amino group at the C5 position, which could enhance the binding ability for silalyllactose which has a negatively-charged carboxyl group. The dissociation constant of the aptamer that showed the strongest sialyllactose-binding ability among the clones of the aptamers was 4.9 microM.


Relative stimulation of aspartate aminotransferase activity in human serum by pyridoxal 5'-phosphate in myocardial infarction.
The relative stimulation of aspartate aminotransferase was investigated in human serum by saturation of apoaspartate aminotransferase with pyridoxal 5'-phosphate. This stimulation depended on the time-course after injury and the peak level was attained later than the maximum value of aspartate aminotransferase activity.


In vivo studies in Syrian golden hamsters: a transplacental bioassay of ten nitrosamines.
The carcinogenic effects of low doses of 10 nitrosamines were determined in pregnant Syrian golden hamsters and their offspring. Compounds studied included dimethylnitrosamine, di-n-propylnitrosamine, di-n-butylnitrosamine, nitrosopiperidine, nitrosohexamethyleneimine, 2-dydroxypropyl-propyl-nitrosamine, 2-oxopropyl-propyl-nitrosamine, methylpropylnitrosamine, di(2-hydroxypropyl) nitrosamine, and 4-hydroxybutyl-butyl-nitrosamine. Tumor incidences of all organ systems were almost always higher and latencies shorter in the mothers than in the offspring. Exceptions occurred in the respiratory system in which several compounds induced a low incidence of tumors in the offspring but none in the mothers. Fetal susceptibility appeared greatest toward the end of gestation. For purposes of bioassay, transplacental exposure was less efficient than conventional adult treatment.


Impact of the adolescent pertussis booster dose on the incidence of pertussis in British Columbia and Quebec, Canada.
Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14-15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15-19-years-old to infants <1-year-old decreased following introduction of the Tdap program and were significantly halved during the 2009-2012 post-Tdap versus 2000-2003 pre-Tdap period. This program impact, however, is tempered by the observation that pertussis incidence among 15-19-year-olds was already lower than any other pediatric age group, following gradual decline from pre-teen rates even before the Tdap program. The risk of hospitalization among adolescents 15-19-years-old was also low throughout at <1/100,000. Furthermore, IRRs increased in 2013-2017 when an increasing proportion of 15-19-year-olds were primed with acellular pertussis vaccine only, suggesting short-lived Tdap booster-dose effectiveness that warrants further monitoring.


Post-VX exposure treatment of rats with engineered phosphotriesterases.
The biologically stable and highly toxic organophosphorus nerve agent (OP) VX poses a major health threat. Standard medical therapy, consisting of reactivators and competitive muscarinic receptor antagonists, is insufficient. Recently, two engineered mutants of the Brevundimonas diminuta phosphotriesterase (PTE) with enhanced catalytic efficiency (kcat/KM = 21 to 38 × 106 M-1 min-1) towards VX and a preferential hydrolysis of the more toxic P(-) enantiomer were described: PTE-C23(R152E)-PAS(100)-10-2-C3(I106A/C59V/C227V/E71K)-PAS(200) (PTE-2), a single-chain bispecific enzyme with a PAS linker and tag having enlarged substrate spectrum, and 10-2-C3(C59V/C227V)-PAS(200) (PTE-3), a stabilized homodimeric enzyme with a double PASylation tag (PAS-tag) to reduce plasma clearance. To assess in vivo efficacy, these engineered enzymes were tested in an anesthetized rat model post-VX exposure (~ 2LD50) in comparison with the recombinant wild-type PTE (PTE-1), dosed at 1.0 mg kg-1 i.v.: PTE-2 dosed at 1.3 mg kg-1 i.v. (PTE-2.1) and 2.6 mg kg-1 i.v. (PTE-2.2) and PTE-3 at 1.4 mg kg-1 i.v. Injection of the mutants PTE-2.2 and PTE-3, 5 min after s.c. VX exposure, ensured survival and prevented severe signs of a cholinergic crisis. Inhibition of erythrocyte acetylcholinesterase (AChE) could not be prevented. However, medulla oblongata and diaphragm AChE activity was partially preserved. All animals treated with the wild-type enzyme, PTE-1, showed severe cholinergic signs and died during the observation period of 180 min. PTE-2.1 resulted in the survival of all animals, yet accompanied by severe signs of OP poisoning. This study demonstrates for the first time efficient detoxification in vivo achieved with low doses of heterodimeric PTE-2 as well as PTE-3 and indicates the suitability of these engineered enzymes for the development of highly effective catalytic scavengers directed against VX.


Separation of heavy metals from salts in multicomponent gas by a two-stage dust collection technique.
A Pb and Zn separation method from salts (Na, K, and Cl) in a simulated multicomponent gas generated by the incineration fly ash melting is studied. The heavy metals are separated using a two-stage dust collection technique. A standard reagents mixture is volatilized by heating in a lab-scale reactor to generate the simulated multicomponent gas. The volatilized salts in the gas are condensed and collected by a filter at a high temperature (600-800 °C), allowing Pb and Zn to pass through the filter as gaseous species. The gaseous heavy metals are condensed by lowering their temperature to 100 °C and collected. The metal separation is promoted by elevating the temperature used in the first-stage dust collection to 800 °C and maintaining a reductive atmosphere in the reactor. Subsequently, a sequential chemical extraction is performed on the obtained materials to evaluate the metals leaching characteristics from the materials. In the separated salts to be landfilled, a portion of toxic metals such as Pb, Cd, As, and Cr remain as water-soluble compounds. The separated Pb and Zn, to be extracted and recovered with precipitation for the metal enrichment, can be extracted using water, acid (pH 3), or CH₃COONH₄ solution (1M).


Potential impacts of climate-related decline of seafood harvest on nutritional status of coastal First Nations in British Columbia, Canada.
Traditional food systems are under pressure from various stressors, including climate change which is projected to negatively alter the abundance of marine species harvested by coastal First Nations (FNs) in British Columbia (BC). To model the potential impacts of the climate-related declines in seafood production on the nutritional status of coastal BC FNs. In addition, we projected potential changes in nutrient intakes, under different scenarios of substitution where traditional seafood is replaced with alternative non-traditional foods. The study design is a mixed-method approach that combines two datasets: projected scenarios of climate-related change on seafood catch potential for coastal BC FNs and data derived from the cross-sectional First Nations Food, Nutrition, and Environment Study. The consumption of seafood was estimated using a food frequency questionnaire among 356 FNs. The contribution of seafood consumption to protein, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamins (A, B12, D, niacin), and minerals (zinc, selenium and iron) requirements was assessed using Dietary Reference Intakes (DRIs). Traditional seafood consumption provided daily recommendations of EPA+DHA (74-184%) and vitamin B12 (84-152%) and substantial levels of niacin (28-55%), selenium (29-55%), vitamin D (15-30%) and protein (14-30%). Projected climate change was estimated to reduce the intakes of essential nutrients by 21% and 31% under 'strong mitigation' (Representative Concentration Pathway, RCP2.6) and 'business-as-usual' (RCP8.5) climate change scenarios, respectively, by the year 2050 relative to 2000. The hypothetical substitution of seafood with selected alternative non-traditional foods does not provide adequate amounts of nutrients. Traditionally-harvested seafood remains fundamental to the contemporary diet and health of coastal BC FNs. Potential dietary shifts aggravated by climate-related declines in seafood consumption may have significant nutritional and health implications for BC FN. Strategies to improve access to seafood harvest potential in coastal communities are needed to ensure nutritional health and overall well-being and to promote food security and food sovereignty in coastal FNs.


A model for the three-dimensional structure of peptidoglycan in staphylococci.
Although the monomeric units of peptidoglycan in Staphylococcus aureus and other staphylococci are well known, the complete structure of the peptidoglycan has not been elucidated. The peptidoglycan monomeric unit may be divided into three parts: (1) glycan chain piece, consisting of N-acetylglucosaminyl-N-acetylmuramic acid; (2) connecting peptide extending from L-alanine to the alpha-amino group of L-lysine; (3) peptide chain piece, consisting of D-alanine, the remainder of L-lysine not included in the connecting peptide, and pentaglycine (S. aureus) or mixed glycine and serine residues (other staphylococci) attached to the epsilon amino group of lysine. The deformation of cross wall into hemisphere in the course of cell division, the distensibility of peptidoglycan, and the appearance of circular (? spiral) lines in the cross wall and on the surface of the newly-formed hemisphere are clues to the structure of peptidoglycan. In the proposed model, cross wall is formed as a linear spiral with 20 turns extending in a plane from periphery to center of the cell. During cell division, the cross wall is bisected. The cross wall spiral becomes a spiral forming the peripheral wall of a new hemisphere. The width of the spiral on the cell surface is maintained by rigid glycan chains and by covalent bonds linking turns of the spiral. The length of the spiral is about 30 times the diameter of the cell. Flexible polypeptide sheets consisting of parallel polypeptide chains run along the length of the spiral. Individual polypeptides contain an average of ten peptide chain pieces. The glycan chain is a helix with two disaccharide residues per turn; consequently consecutive connecting peptides project in opposite directions and are perpendicular both to the glycan chain and to the peptide chain. In cross wall, hydrogen bonding between polypeptide chains enables the polypeptide sheet to transmit changes in tension. The deformation of cross wall into peripheral wall requires doubling of the external surface area of the peptidoglycan. A change in the angle of the glycan chain with respect to the peptide chain results in an increase of the distance between peptide chains, causing the doubling of surface area. Implications of the model include explanations for the initiation of cell division and for the existence of osmotically growth-dependent staphylococci.


Induction of stress proteins in anoxic and hyperthermicSpodoptera frugiperda cells.
In this study, we compare stress protein induction in anoxic and hyperthermicSpodoptera frugiperda cells. Anoxia transiently induces a cluster of heat shock proteins at 71 and 72 kDa. This is a subset of a larger group of stress proteins induced by heat shock. Several heat shock proteins reported in this study were previously undetected inS. frugiperda. With these additional proteins, the stress response of hyperthermicS. frugiperda closely resembles that ofDrosophila melanogaster. Prior investigations of stress protein induction during oxygen deprivation focused on mammalian cells. In sharp contrast to these cells, anoxicS. frugiperda cells neither induce glucose-regulated proteins nor suppress the heat shock family of 71/72 kDa proteins. These findings provide insight into the virtually unexplored area of stress protein induction in anoxic insect cells. In addition, they help to explain the effects of oxygen deprivation on heterologous protein yield from virally infected insect cells and to develop an oxygenregulated promoter for stably transformed insect cells.


Mapping home internet activity during COVID-19 lockdown to identify occupation related inequalities.
During the COVID-19 pandemic, evidence has accumulated that movement restrictions enacted to combat virus spread produce disparate consequences along socioeconomic lines. We investigate the hypothesis that people engaged in financially secure employment are better able to adhere to mobility restrictions, due to occupational factors that link the capacity for flexible work arrangements to income security. We use high-resolution spatial data on household internet traffic as a surrogate for adaptation to home-based work, together with the geographical clustering of occupation types, to investigate the relationship between occupational factors and increased internet traffic during work hours under lockdown in two Australian cities. By testing our hypothesis based on the observed trends, and exploring demographic factors associated with divergences from our hypothesis, we are left with a picture of unequal impact dominated by two major influences: the types of occupations in which people are engaged, and the composition of households and families. During lockdown, increased internet traffic was correlated with income security and, when school activity was conducted remotely, to the proportion of families with children. Our findings suggest that response planning and provision of social and economic support for residents within lockdown areas should explicitly account for income security and household structure. Overall, the results we present contribute to the emerging picture of the impacts of COVID-19 on human behaviour, and will help policy makers to understand the balance between public health and social impact in making decisions about mitigation policies.


Association Between Bleeding and New Cancer Detection and the Prognosis in Patients With Myocardial Infarction.
Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all-cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50-4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30-29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69-57.07]). The risk of all-cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04-8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81-9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.


Frequency of Hepatitis B and C Viruses, and HIV Among Drug Addicts in the Eastern Anatolia, Turkey.
Hepatitis B, hepatitis C and HIV infections constitute serious healthcare problems worldwide. There are a limited number of studies regarding the prevalence of hepatitis B, hepatitis C and HIV infections among the drug addicts in Turkey; hence, the current study aimed to determine the frequency of these infections among 235 drug addicts treated in a drug addiction treatment centre/Elazig, Turkey. HBsAg, anti-HBs, anti-HCV and anti-HIV tests in 235 drug addicts were studied by ELISA technique. Urine samples obtained from drug addicts were analyzed for cannabis, opiate and cocaine metabolites. All the 235 drug users were males, and their mean age was 30.69 ± 9.494 years; 112 (47.7%) of them were in the age group ranging 20 - 29 years (P < 0.05). Of 235 drug addicts, 113 (48.1%) and 115 (48.9%) were only cannabis and opiate users, respectively. In urine samples of seven (3%) drug addicts both cannabis and opiate metabolites were detected. Cocaine was detected in none of the urine samples. The frequencies of HBsAg, anti-HBs and anti-HCV among drug addicts were 2.6%, 38.3%, and 9.4%, respectively. None of the drug addicts was positive for HIV. Anti-HCV was more prevalent in opiate users than in cannabis users: 15.7% vs. 1.8% (P < 0.001). The obtained results showed that HCV infection was an alarming problem among opiate users in the eastern part of Turkey. It is suggested to rapidly diagnose the infected persons; thus preventive measures and appropriate control may limit further transmission of these infections.


Strategies for studying the ligand binding site of GPCRs: photoaffinity labeling of the VPAC1 receptor, a prototype of class B GPCRs.
G protein-coupled receptors (GPCRs) are crucial receptors acting as molecular sensors for many physiological and pathological processes. Class B GPCRs represent a small GPCR subfamily encompassing 15 members, and are very promising targets for the development of drugs to improve many diseases such as chronic inflammation, neurodegeneration, diabetes, stress, and osteoporosis. Over the past decade, structure-function relationship studies have demonstrated that the N-terminal ectodomain (N-ted) of class B GPCRs plays a pivotal role in natural ligand recognition. The N-ted structure of some class B GPCRs folds into a Sushi domain consisting of two antiparallel β sheets stabilized by three disulfide bonds and a salt bridge. The VPAC1 receptor is an archetype of class B GPCRs that binds vasoactive intestinal peptide (VIP), a neuropeptide modulating many physiological processes. The structure-function relationship of VPAC1 has been extensively studied. The use of a photoaffinity labeling strategy has been a powerful approach to determine the physical contacts between the functional receptor and its ligand. Those studies, coupled with 3D molecular modeling techniques, have clearly demonstrated the crucial role of the VPAC1 receptor N-ted in VIP recognition.


Epigenetic regulation of genomic integrity.
Inefficient and inaccurate repair of DNA damage is the principal cause of DNA mutations, chromosomal aberrations, and carcinogenesis. Numerous multiple-step DNA repair pathways exist whose deployment depends on the nature of the DNA lesion. Common to all eukaryotic DNA repair pathways is the need to unravel the compacted chromatin structure to facilitate access of the repair machinery to the DNA and restoration of the original chromatin state afterward. Accordingly, our cells utilize a plethora of coordinated mechanisms to locally open up the chromatin structure to reveal the underlying DNA sequence and to orchestrate the efficient and accurate repair of DNA lesions. Here we review changes to the chromatin structure that are intrinsic to the DNA damage response and the available mechanistic insight into how these chromatin changes facilitate distinct stages of the DNA damage repair pathways to maintain genomic stability.


The initial social encounters of high and low social effectiveness school-aged children.
The initial social encounters of 30 pairs of unacquainted high/high, high/low, and low/low popularity status third- and fourth-grade boys and girls were observed in an analogue free-play setting. Pairwise comparisons revealed that the dyads did not differ according to pairing on the exchange of global play information. The low/low popularity dyads, as compared to the high/high and the high/low popularity dyads, exchanged significantly less personal information as indexed by both the patterns and the content of personal information exchange. Analyses revealed no differences between the high/high and high/low dyads on the patterns and content of personal information exchange. However, as compared to the high/high dyads, the high/low dyads and the low/low dyads were less likely to evidence a pattern of initial steps in their social encounters that began with greeting and introduction and that was followed by the exchange of play information. The observations of the high/high dyads were considered as a model for developing social skills training programs designed to facilitate acquaintanceship development, and the need for further research on the processes underlying peer pairing and the components of social skillfulness was discussed.


In vitro embryo production and embryo transfer in domestic and non-domestic cats.
Over a 5-year interval, multiple laparoscopic oocyte retrievals were done in fishing cats (Prionailurus viverrinus), caracals (Caracal caracal) and domestic cats after ovarian stimulation with gonadotropins. From 21 retrievals in five fishing cats, 579 preovulatory oocytes (mean = 27.6) were recovered and 348 embryos were produced in vitro (mean = 16.6). A total of 452 preovulatory oocytes (mean = 25.1) were recovered from 18 of 24 retrievals in six caracals and 297 (mean = 16.6) embryos were produced. An additional 16 caracal embryos (19%) were produced after in vitro maturation of 83 oocytes, 59 of which came from six retrievals producing only immature oocytes. The presence of corpora lutea at oocyte retrieval occurred in each species (1) at a similar frequency (33%) and (2) more frequently during January through May (11 of 15 retrievals) than during the latter half of the year (4 of 30 retrievals). Of the 12 embryo transfer procedures done in fishing cats, one pregnancy (8%) was obtained and one live kitten born after the auto-transfer of 10 Day-6 embryos. In caracals, a total of 46 Day-4 or Day-5 embryos were auto-transferred to six recipients, one of which delivered two live kittens. Then, 109 caracal embryos were cryopreserved before thawing and transferring to nine recipients (mean = 12.1) on Days 5 or 6. From three pregnancies established (33%), a total of three kittens were born. Two to six gonadotropin treatments/oocyte retrievals were done in domestic cats during 1999 through 2003; an average of 24.9, 23.5, 22.0, 23.1, 23.5 and 40.9 oocytes (P > 0.05) were recovered at the first through the sixth treatment cycles from 138, 138, 97, 49, 22, and seven retrievals, respectively.


The incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation: comparison of warfarin and dabigatran.
Cerebral microthromboembolism after atrial fibrillation (AF) ablation has been reported in 4-20% with perioperative warfarin. Dabigatran is a new anticoagulant in patients with nonvalvular AF. We investigated the incidence of asymptomatic cerebral microthromboembolism after AF ablation with perioperative warfarin or dabigatran using diffusion-weighted and T2-weighted magnetic resonance imaging (MRI). Our study included 210 consecutive patients with AF (111 paroxysmal and 99 persistent) who underwent complex fractionated atrial electrogram-guided ablation (combined with pulmonary vein isolation, n = 110). Catheter irrigation was performed in all cases. Uninterrupted warfarin therapy was used in 180 patients (warfarin group) and interrupted only on the morning of the procedure with dabigatran in 30 (dabigatran group). All patients underwent cerebral MRI the day after ablation. New microthromboemboli were detected in 10.0% of the warfarin group and 26.7% of the dabigatran group (P < 0.05). The incidence of hemopericardium treated with pericardiocentesis was lower in the warfarin group than in the dabigatran group (2.5% vs 11.1%, P < 0.05). In multivariate analysis, the use of cardioversion was a predictor of new microthromboembolism development after AF ablation. The incidence of asymptomatic cerebral microthromboembolism and hemopericardium after AF ablation was significantly lower with perioperative warfarin therapy than with dabigatran therapy. Dabigatran may not be an effective alternative to warfarin for AF ablation, especially in patients who undergo cardioversion.


Can intensity-modulated radiotherapy preserve oral health-related quality of life of nasopharyngeal carcinoma patients?
To investigate the changes in salivary function and oral health-related quality of life for patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy (IMRT). A total of 57 patients with early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva flow was measured, and the Medical Outcomes Study 36-item short form, European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire 35-item head-and-neck module, and Oral Health Impact Profile questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months after IMRT. Parotid saliva flow recovered fully after 1 year and maintained. Whole saliva flow recovered partially to 40% of baseline. A general trend of deterioration in most quality of life scales was observed after IMRT, followed by gradual recovery. Persistent oral-related symptoms were found 2 years after treatment. IMRT for early-stage nasopharyngeal carcinoma could only partially preserve the whole salivary function and oral health-related quality of life.


Some histochemical observations on the myocardial metabolism in experimental conditions. Part I.
In the paper the author is concerned with the histochemical estimation of the metabolic adaptation of the heart muscle of albino rats during an early experimental alloxan diabetes. It has been found that the state of experimentally produced insulin deficiency directly influences metabolism of the heart muscle and the changes observed in the histochemical reactions prove this. An increase in the intensity of histochemical reactions concerns the PAS-positive reaction and the reactions to the NADH and NADPH tetrazole reductase activities. Alkaline phosphatase shows a decrease in the enzymatic activity, whose nature is transitional and reversible with regard to cytochrome oxidase and ATP-ase. The histochemical picture of metabolic changes depends on the duration time of experimental diabetes.


Polycystin-2 associates with the polycystin-1 homolog, suREJ3, and localizes to the acrosomal region of sea urchin spermatozoa.
Polycystin-2, the protein mutated in type 2 autosomal dominant polycystic kidney disease, is an integral transmembrane protein with nonselective cation channel activity. Here we report on the sea urchin sperm homolog of polycystin-2 (suPC2). Like other polycystin-2 family members, suPC2 is a six-pass transmembrane protein containing C-terminal cytoplasmic EF hand and coiled-coil domains. The protein localizes exclusively to the plasma membrane over the sperm acrosomal vesicle. This localization coincides with the previously reported localization of the sea urchin PC1 homolog, suREJ3. Co-immunoprecipitation shows that suPC2 and suREJ3 are associated in the membrane. The location of suPC2 suggests that it may function as a cation channel mediating the sperm acrosome reaction. The low cation selectivity of PC2 channels would explain data indicating that Na(+) and Ca(2+) may enter sea urchin sperm through the same channel during the acrosome reaction.


Multidisciplinary protocol for rapid head computed tomography turnaround time in acute stroke patients.
The door-to-computed tomography (CT) head reporting time is an essential step to determining eligibility for thrombolysis in acute stroke patients, but the specific components of the process have not been reported in detail. We performed a retrospective cross-sectional analysis of the prospectively collected Get-With-The-Guidelines database in our comprehensive stroke center to evaluate the effect of a structured multidisciplinary protocol on head CT times in acute stroke patients under consideration for thrombolysis. The median CT turnaround time in the first 6-month period was 27 (interquartile range [IQR], 27) and decreased in all subsequent periods after implementation of a formal protocol to 18 (IQR, 12; range, 17-20 minutes; P < .0001 for all pairwise comparisons). The median CT turnaround time was 18 (IQR, 12) versus 20 (IQR, 14) minutes for patients with admission diagnosis of stroke (n = 1123) versus nonstroke (n = 685; P < .0001), respectively. A structured multidisciplinary protocol for obtaining acute stroke protocol head CT scan was associated with reduced CT turnaround time over the study period. Prospective studies should be done to determine if implementation in other stroke centers confirms the effectiveness of our protocol.


Termination of ventricular tachycardia by chest wall stimulation during DDD pacing. A report of two cases.
This report describes the use of chest wall stimulation (CWS) for the termination of ventricular tachycardia in two patients with dual chamber pulse generators functioning in the DDD mode. Rapid CWS induced burst ventricular pacing when CWS was selectively sensed by the atrial channel, whereupon the pulse generator triggered its ventricular output. In this way, by programming the pulse generators to the maximum upper rate, this CWS technique produced burst ventricular pacing at a rate of 175 to 180/minute that successfully terminated ventricular tachycardia in both patients. The same CWS technique also initiated ventricular tachycardia by burst ventricular pacing. This CWS technique may be useful for the termination of relatively slow ventricular tachycardia in patients with DDD pulse generators when the maximum rate of ventricular pacing cannot be otherwise increased.


Analysis of human peripheral blood mononuclear cells bearing Fc receptors for the three major immunoglobulin isotypes.
Fluorochrome-labeled, human immunoglobulins (Igs) were used to characterize peripheral blood mononuclear cell (PBMC) subsets that had Fc receptors (FcRs) for the three major isotype classes, IgG, IgA and IgM. Relatively high concentrations of these Igs were needed to saturate FcRs. However, by a number of criteria, competition assays in particular, isotype-specific FcR binding was shown. In vivo bound Ig was directly measured by anti-Fc class-specific F(ab)2 antibodies. With the exception of monocytes, where a mean of 19% had in vivo bound IgG, only small percentages of other PBMC subsets had any type of in vivo bound Ig. Studies done on a large group of normal individuals revealed that approximately 27% of all PBMCs had gamma, 24% alpha, and 23% microFcRs. Dual fluorescence assays were performed to determine the gamma, alpha, and microFcR status on T, B, NK cells and on monocytes. The majority of staining for gamma, alpha, and microFcRs was accounted for by the numerically largest subfraction, the T cells. However, when FcR status was determined for each subset virtually all had either gamma, alpha, or microFcRs--94% of CD2+, 98% of CD4+, 73% of CD8+, 100% of CD19+, 100% of CDw19+, 92% of Leu 7+, and 61% of Leu 11+ cells. All three FcRs were expressed within each subset. Of interest, a small percentage of unfractionated and monocyte-depleted PBMCs coexpressed one of three pairs of FcRs, either alpha and gamma, alpha and mu, or mu and gamma.


Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but only partially with oocyte maturity.
Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure then, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from 13C-labeled substrates resulting in an M + 2 isotopologue that contains 2 13C atoms. Comparing the fate of three major carbon sources, mean enrichment of M + 2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate in 278 CCs from 21 women ≤34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p = 0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M + 2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: -6.02, CI: -1.74,-13.79, p = 0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility.Abbreviations: CCs: cumulus cells; COC: cumulus-oocyte complex; LC-MS: liquid chromatography-mass spectrometry; acetyl-CoA: acetyl-Coenzyme A; CoA: Coenzyme A.


Responses of Vallisneria natans (Lour.) Hara to the combined effects of Mn and pH.
Aquatic plants play a vital role in maintaining the health and stability of ecosystems and in ecological restoration of contaminated water bodies. Herein, a 21-day-long laboratory-scale experiment was designed to explore the growth and physiological responses of Vallisneria natans (Lour.) Hara (V. natans) to the combined effects of manganese (Mn, 5, 20, and 80 mg L-1) and pH (pH 4.0, 5.5, and 7.0). Our results showed the combined toxicity intensity was closely related to Mn concentration and the toxicity exhibited by Mn gradually strengthened with the decrease of pH level. High concentration of Mn stress significantly reduced plants leaf area, final leaf number, photosynthetic pigment content, RGR (relative growth rate) and biomass accumulation, but significantly increased the contents of malondialdehyde (MDA) and hydrogen peroxide (H2O2). At the same time, V. natans plants can resist the adverse stress by activating the antioxidant defense system, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO) activities. Besides, V. natans tended to adjust the biomass allocation strategy and transferred more energy to the subsurface and the ramets and stolons parts under the combined stress. This experiment also showed that the increasing pH within a certain range could largely improve the removal rate of Mn (at highest by 84.28%). This may indicate the V. natans plant species can act as a promising tool for the Mn phytoremediation in aquatic environments which needs to be further explored by longer cycle field studies.


Novel Approach to the Detection of Left Ventricular Hypertrophy Using Body Mass Index-Corrected Electrocardiographic Voltage Criteria in a Group of African Ancestry.
Electrocardiographic (ECG) QRS voltages used to generate criteria for left ventricular hypertrophy (LVH) detection are considerably attenuated by obesity. This effect renders the utility of ECG criteria to detect LVH in obese individuals of African ancestry to be of limited value. A novel approach to correcting QRS voltages for the attenuating effect of body mass index (BMI) will improve the ability of ECG criteria to detect LVH in a group of African descent. Left ventricular mass was determined from echocardiography in 661 randomly selected participants (43.0% obese) of black African ancestry in South Africa. As compared with Cornell and Sokolow-Lyon voltage criteria, BMI best correlated with RaVL , Gubner-Ungerleider, and Lewis QRS complex voltages, but these relations were noted only in those with BMI <29 kg/m(2) . Correcting RaVL and Lewis voltages by the difference in the slope of BMI-voltage relations in those with BMI <29 kg/m(2) vs those with BMI ≥29 kg/m(2) showed the greatest performance for LVH detection (uncorrected RaVL : 0.695 ± 0.025, corrected RaVL : 0.733 ± 0.022; P < 0.0001), and also increased the sensitivity (uncorrected RaVL : 30.6%, corrected RaVL : 42.4%; P < 0.0005) with no significant change in specificity (uncorrected RaVL : 86.3%, corrected RaVL : 83.0%; P = 0.28). We offer a novel approach to correcting ECG voltages for the attenuating effects of obesity in individuals of African ancestry, and this improves the performance and sensitivity for LVH detection.


Intracellular oxidative modification of low density lipoprotein by endothelial cells.
We investigated intracellular oxidative modification of low density lipoprotein (IOM-LDL) by endothelial cells (ECs) and the role of ferritin in this process. IOM-LDL was examined by immunocytochemistry with an anti-oxidized phosphatidylcholine antibody and by lipid peroxidation assay. Incubation of LDL-treated ECs (human umbilical vein endothelial cells, passage 3) with ferritin produced cytoplasmic immunostain with the antibody, especially in large or giant ECs, and the formation of thiobarbituric acid-reactive substance (TBARS) in these cells. These observations suggest that ECs can perform IOM-LDL. Incubation with the iron chelator deferoxamine or pretreatment of LDL-treated ECs with deferoxamine suppressed ferritin-induced IOM-LDL by greater than 60%. Antioxidants dimethylsulphoxide and butylated hydroxytoluene markedly inhibited IOM-LDL, but mannitol did so only mildly. Catalase and superoxide dismutase had little or no effect on IOM-LDL. Apoferritin substituted for ferritin did not induce IOM-LDL. Our data suggest that IOM-LDL is mediated by intracellular hydroxyl radical formation, which is catalyzed mainly by free iron released from ferritin, and that ECs contribute to the development of atherosclerosis via IOM-LDL.


Case report: periosteal new bone formation in Takayasu arteritis.
Periosteal new bone formation is recognized as a rare feature of arteritis but has not previously been described in association with Takayasu arteritis. We report the first case of Takayasu arteritis complicated by multifocal periosteal new bone formation of both clavicles and one scapula.


Models of neurological disease (substance abuse): self-administration in monkeys.
Drug self-administration is a procedure in which a subject performs a specified response that results in the delivery of a drug injection. This procedure is viewed as a relevant model for the study of human drug-taking behavior. Drug self-administration in primates has several characteristics that resemble drug-taking behavior in humans, and agents commonly abused by humans also generally maintain self-administration behavior in monkeys. Self-administration procedures allow for the study of a variety of drug properties. For instance, they can be used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of drug addiction. These procedures can also be employed for examining drug reinforcement mechanisms. Described in this unit are procedures for studying intravenous drug self-administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.


Glucose control during Ramadan in a pediatric cohort with type 1 diabetes on MiniMed standard and advanced hybrid closed‑loop systems: A pilot study.
Hybrid closed-loop (HCL) systems have revolutionized the treatment of diabetes, enabling doctors to cope with challenging conditions that were previously almost impossible to manage or were very risky and difficult. To assess the efficacy and safety of a hybrid closed-loop (HCL) system during Ramadan fasting in a pediatric cohort with type 1 diabetes (T1D). Glucose control outcomes in older children and adolescents aged 8-16 years with automated insulin delivery for T1D were analyzed during Ramadan and 1 month before Ramadan. Participants on MiniMed standard HCL (670G) or advanced HCL (780G) systems of Medtronic were categorized as fasting or nonfasting. The average age of the 19 participants (8 and 11 were on standard and advanced HCL systems, respectively) was 11.35 ± 2 years. Eleven patients fasted during Ramadan. Pump setup and sensor statistics were the same during Ramadan and the month before; no significant difference was found between the two groups in terms of insulin and glucose control metrics, with practically the same coefficient of variation, time in range (TIR) and time spent in hypoglycemia, maintained within the international recommended targets. Total daily doses were paradoxically higher in patients who fasted during Ramadan (p = 0.01), without repercussions on glucose control metrics. Standard and advanced HCL use during Ramadan were safe and were associated with a maintained optimum TIR (>70 %) and no significant hypoglycemia in adolescents and older children with T1D.


Comparison of Outcomes of Hepatic Resection and Radiofrequency Ablation for Hepatocellular Carcinoma Patients with Multifocal Tumors Meeting the Barcelona-Clinic Liver Cancer Stage A Classification.
Although hepatic resection (HR) has been recommended as the first-line treatment option for patients with a solitary tumor, the first-line treatment for patients with multifocal tumors meeting the Barcelona-Clinic Liver Cancer (BCLC) stage A still remains unclear. This study compared outcomes for patients with multifocal tumors meeting the BCLC stage A treated by HR and radiofrequency ablation (RFA). A total of 384 consecutive patients with multifocal tumors meeting the BCLC stage A, who underwent HR (n = 224) or RFA (n = 160), were included. Moreover, propensity score-matched patients were analyzed to adjust for baseline differences. The 1-, 3-, and 5-year overall survival (OS) rates after HR and RFA were 96%, 71.7%, and 36.3%, and 90.0%, 72.7%, and 37.8%, respectively (p = 0.609); HR provided significantly better recurrence-free survival (RFS) rates than RFA at 1, 3, and 5 years (87.5%, 53.1%, and 20.1% vs 83.1%, 34.0%, and 9.7%, respectively, p = 0.001). Patients selected in the propensity-matching model showed similar results. Subgroup analysis also showed that HR was associated with better RFS than RFA for patients with 2 tumors, multifocal tumors located in the same lobe (Couinaud's segmentation) and segment (Takasaki's segmentation). Multivariate analysis revealed that 3 tumors, portal hypertension, and tumors located in different segments (Takasaki's segmentation) are independent predictors of poor prognosis in patients with multifocal tumors meeting the BCLC stage A. For patients with multifocal tumors meeting the BCLC stage A, HR may offer significantly better RFS than RFA, and HR may be considered as the first-line treatment option for those patients.


Polyrhythmic foraging and competitive coexistence.
The current ecological understanding still does not fully explain how biodiversity is maintained. One strategy to address this issue is to contrast theoretical prediction with real competitive communities where diverse species share limited resources. I present, in this study, a new competitive coexistence theory-diversity of biological rhythms. I show that diversity in activity cycles plays a key role in coexistence of competing species, using a two predator-one prey system with diel, monthly, and annual cycles for predator foraging. Competitive exclusion always occurs without activity cycles. Activity cycles do, however, allow for coexistence. Furthermore, each activity cycle plays a different role in coexistence, and coupling of activity cycles can synergistically broaden the coexistence region. Thus, with all activity cycles, the coexistence region is maximal. The present results suggest that polyrhythmic changes in biological activity in response to the earth's rotation and revolution are key to competitive coexistence. Also, temporal niche shifts caused by environmental changes can easily eliminate competitive coexistence.


Comparison of calcium, calcitriol, ovarian hormones and nandrolone in the treatment of osteoporosis.
Most therapy for osteoporosis has been aimed at decreasing bone resorption and is capable of preventing further bone loss. Recently, anabolic steroids have been claimed to cause increased bone mass in osteoporosis, but the mechanism for this effect is not understood. In this study calcium, and calcium with calcitriol, caused a slowing of forearm bone mineral loss. Calcium and ovarian hormones, with or without calcitriol, caused a small non-significant rise in forearm mineral density, and nandrolone decanoate 50 mg intramuscularly, every 2 or 3 weeks caused a significant rise in forearm mineral density (+15.9 +/- 2.4 mg/ml/yr and +13.7 +/- 3.4 mg/ml/yr, respectively). The 3-weekly regime caused few side effects and is considered the optimal dose. The striking rise in bone density in patients in whom bone resorption was controlled before therapy, suggests that anabolic steroids can increase the bone formation rate.


SARS-CoV-2 infections in households in a peri-urban community of Lima, Peru: A prospective cohort study.
We assessed the prevalence and incidence of SARS-CoV-2 infections in a prospective study of households in Lima, Peru. Households with a child, a young adult 18-50 years, and an adult age >50 years in peri-urban Lima were followed with twice-a-week household visits during a 2-month period. Nasal swabs and saliva specimens were collected twice weekly, and nasopharyngeal swabs were collected weekly from each participant, regardless of symptoms. Laboratory-confirmed SARS-CoV-2 infection was defined by two RT-PCR tests from any of the collected specimens within a week. Blood samples collected at enrollment and end of follow-up were tested with rapid serological tests. We calculated the prevalence and incidence of laboratory-confirmed SARS-CoV-2 infections. We enrolled 132 participants from 44 households: 44 children, 44 young adults, and 44 older adults. A total of 13 SARS-CoV-2 infections were detected in eight households, for an overall period prevalence of 9.85% (95% confidence interval [CI]: 5.35-16.25). Most (61.54%) infections were symptomatic. Eight of 11 (72.73%) SARS-CoV-2 detections corresponded to the Lambda variant. During 218.79 person-months at risk of follow-up, there were six new SARS-CoV-2 infections detected (2.74 per 100 person-month, 95% CI: 1.25-6.04). At enrollment, 59 of 128 participants tested had positive SARS-CoV-2 IgG serology (46.09%, 95% CI: 37.25-55.12). Five of six new infections occurred among participants with negative baseline serology. We demonstrated high incidence of SARS-CoV-2 infections in households, especially among subjects without evidence of prior infection, most of them not detected by the Ministry of Health system.


[Concepts of lesion development in multiple sclerosis. Current approaches and clinical-therapeutic implications ].
The pathogenesis and development of lesions in multiple sclerosis (MS) are still unexplained and are the subject of some controversy. On the basis of histopathological analysis of a small set of MS cases, a recently published study postulates primary oligodendroglial damage as the initiator of MS lesions, with infiltration of leukocytes into the central nervous system (CNS) as a secondary phenomenon. In this paper we outline the current controversial discussion and different concepts of lesion development in MS. We conclude that demyelination can result from different pathogenic mechanisms, with either primary autoimmune inflammation or primary oligodendroglial damage and a secondary inflammatory reaction. Lesions can be divided into four subtypes (patterns I-IV) on the basis of histopathological characteristics, which supports the idea that MS lesions develop in different ways. These new aspects may have major implications for treatment. However, except in a few specific forms, most MS patients cannot currently be assigned to one of these lesion subtypes by means of clinical and paraclinical parameters. Without this, individual treatments tailored to the pathogenesis will not be possible.


Pancreatic ascites and pleural effusion treated by endoscopic pancreatic stent placement.
Usefulness of endoscopic pancreatic stents in the management of pancreatic ascites and pleural effusion has been evaluated only recently. We report a patient with alcoholic pancreatitis who presented with ascites and pleural effusion and had a pancreatic duct disruption in the body area on pancreaticography. A 5 F stent was placed across the disruption with rapid subsidence of both ascites and pleural effusion. The stent was removed after 12 weeks and there has been no recurrence during a follow-up period of 9 months.


The detection and significance of subtle changes in mixed-signal brain lesions by serial MRI scan matching and spatial normalization.
The purpose of this work is to detect and assess the significance of subtle signal changes in mixed-signal lesions based on serial MRI scan matching. Pairs of serially acquired T1-weighted volume MR images from 20 normal controls and seven patients with epilepsy were matched and difference images obtained. The precision and consistency of the registration were evaluated. The Gaussian noise level in the difference images was determined automatically. A structured difference filter was then used to segment structured (changed) voxels from the Gaussian noise. In the controls, the structured difference images were normalized into Talairach space, resulting in a structured noise map. The significance of changes in patients was assessed by spatial normalization and comparison with the structured noise map. The precision and consistency of the co-registration were < or = 0.06 mm with a registration success rate of 100%. The Gaussian noise level in the difference images was in the range 3.0-6.9. In the controls, an average of 1.6% of the brain voxels were classified as structured. Sine-based registration resulted in a reduction of < 1% in the amount of structure compared to linear interpolation. The structured noise map in controls showed high noise density in areas affected by image artefacts. We show examples of significant changes found in lesions which had been reported as unchanged on visual inspection. A novel quantitative approach has been presented for the detection and quantification of subtle signal changes in lesions. This method is of potential clinical value in the non-invasive characterization of signal change and biological behaviour of neoplastic lesions.


[Controlled desferrioxamine treatment of congenital anaemia and transfusion siderosis (author's transl)].
A 19-year-old patient with congenital Blackfan-Diamond anaemia has been maintained on a regular red cell transfusion schedule since he was two months old. From the age of four he has received desferrioxamine injections at regular intervals with different dose levels. In spite of the treatment with the chelating agent secondary siderosis developed with typical endocrinological abnormalities and cardiac arrhythmias. Increasing the dose of desferrioxamine to 16 g/24 h resulted in an iron excretion of 184 mg/24 h. Such an intensification of treatment finally produced a negative iron balance and the cardiac arrhythmias disappeared. Desferrioxamine therapy should be done under controlled circumstances only, an iron balance is mandatory, and the dose should be adjusted to the results of the balance.


SARS-CoV-2 N Protein Triggers Acute Lung Injury via Modulating Macrophage Activation and Infiltration in in vitro and in vivo.
SARS-CoV-2-induced acute lung injury but its nucleocapsid (N) and/or Spike (S) protein involvements in the disease pathology remain elusive. In vitro, the cultured THP-1 macrophages were stimulated with alive SARS-CoV-2 virus at different loading dose, N protein or S protein with/without TICAM2-siRNA, TIRAP-siRNA or MyD88-siRNA. The TICAM2, TIRAP and MyD88 expression in the THP-1 cells after N protein stimulation were determined. In vivo, naïve mice or mice with depletion macrophages were injected with N protein or dead SARS-CoV-2. The macrophages in the lung were analyzed with flow cytometry, and lung sections were stained with H&E or immunohistochemistry. Culture supernatants and serum were harvested for cytokines measurements with cytometric bead array. Alive SARS-CoV-2 virus or N protein but not S protein induced high cytokine releases from macrophages in a time or virus loading dependent manner. MyD88 and TIRAP but not TICAM2 were highly involved in macrophage activation triggered by N protein whilst both inhibited with siRNA decreased inflammatory responses. Moreover, N protein and dead SARS-CoV-2 caused systemic inflammation, macrophage accumulation and acute lung injury in mice. Macrophage depletion in mice decreased cytokines in response to N protein. SARS-CoV-2 and its N protein but not S protein induced acute lung injury and systemic inflammation, which was closely related to macrophage activation, infiltration and release cytokines.


Understanding criteria for surveillance of patients with a small renal mass.
To better delineate which factors influence the decision to undergo active surveillance of small renal masses. We identified 204 consecutive patients at our institution with clinical Stage T1 renal masses from June 2009 through June 2010. A variety of demographic and clinical characteristics were measured. Based on our previous work, the "ideal" criteria for active surveillance included tumor size ≤ 4 cm, Charlson comorbidity index of ≥ 2, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≥ 2, and estimated glomerular filtration rate <60 mL/min. We performed sensitivity analyses to identify the characteristics associated with choice of active surveillance and compared these with our "ideal" criteria. Of the 204 patients, 73 (36%) and 131 (64%) underwent active surveillance and treatment, respectively. The patients undergoing active surveillance versus treatment differed with respect to distance from hospital >60 miles (P = .04), ECOG PS of ≥ 2 (P < .01), tumor size (P < .01), multifocality (P = .03), endophytic nature of lesion (P = .04), and whether the patient's surgeon generally used a robotic, laparoscopic, or open approach (P = .01). Neither the baseline estimated glomerular filtration rate (P = .91) nor the Charlson comorbidity index (P = .69) were significant factors. The combination of tumor size <3 cm, ECOG PS of ≥ 2, and an endophytic lesion were most predictive of active surveillance. Patient, tumor, and surgeon characteristics all influence the choice of active surveillance. From the sensitivity analyses, active surveillance was driven by a tumor size <3 cm, poor PS (ie, ECOG PS of ≥ 2), and an endophytic lesion.


Is hypochlorous acid (HOCl) involved in age-related nuclear cataract?
Oxidative damage to lens proteins is associated with human age-related nuclear cataract and H2O2 has been implicated. As hypochlorous acid (HOCl) can be formed from chloride ions and H2O2 and many of the protein modifications observed in cataract are also noted following exposure of proteins to HOCl, age-related nuclear cataract lenses were examined for evidence of HOCl-mediated alterations. Three techniques were employed using human lens samples: 1. staining with a HOP antibody that recognises HOCl-treated proteins, 2. myeloperoxidase assays and 3. measurement of chlorotyrosine in acid digests of the crystallins. HOP staining was inconclusive, although cataract lenses appeared to stain more intensely than normals. No myeloperoxidase activity could be detected and neither mono- nor di-chlorotyrosine could be found in human lens proteins. On the basis of this study, no evidence was obtained to support a role for HOCl in age-related nuclear cataract.


A mathematical model for pulsatile release: controlled release of rhodamine B from UV-crosslinked thermoresponsive thin films.
A controlled drug delivery system fabricated from a thermoresponsive polymer was designed to obtain a pulsatile release profile which was triggered by altering the temperature of the dissolution medium. Two stages of release behaviour were found: fast release for a swollen state and slow (yet significant and non-negligible) release for a collapsed state. Six cycles of pulsatile release between 4 °C and 40 °C were obtained. The dosage of drug (rhodamine B) released in these cycles could be controlled to deliver approximately equal doses by altering the release time in the swollen state. However, for the first cycle, the swollen release rate was found to be large, and the release time could not be made short enough to prevent a larger dose than desired being delivered. A model was developed based on Fick's law which describes pulsatile release mathematically for the first time, and diffusion coefficients at different temperatures (including temperatures corresponding to both the fully swollen and collapsed states) were estimated by fitting the experimental data with the theoretical release profile given by this model. The effect of temperature on the diffusion coefficient was studied and it was found that in the range of the lower critical solution temperature (LCST), the diffusion coefficient increased with decreasing temperature. The model predicts that the effective lifetime of the system lies in the approximate range of 1-42 h (95% of drug released), depending on how long the system was kept at low temperature (below the LCST). Therefore this system can be used to obtain a controllable pulsatile release profile for small molecule drugs thereby enabling optimum therapeutic effects.