Role of cystic fibrosis transmembrane conductance regulator in pulmonary clearance of Pseudomonas aeruginosa in vivo.
Cystic fibrosis (CF)2 is a fatal genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) that is commonly associated with chronic pulmonary infections with mucoid Pseudomonas aeruginosa (PA). To test the hypothesis that CFTR plays a direct role in PA adhesion and clearance, we have used mouse lines expressing varying levels of human (h) or mouse (m) CFTR. A subacute intratracheal dose of 3 x 10(6) bacteria was cleared with similar kinetics in control wild-type (WT) and transgenic mice overexpressing hCFTR in the lung from the surfactant protein C (SP-C) promoter (SP-C-hCFTR+/-). In a second series of experiments, the clearance of an acute intratracheal dose of 1.5 x 10(7) PA bacteria was also similar in WT, hemizygous SP-C-hCFTR+/-, and bitransgenic gut-corrected FABP-hCFTR+/+-mCFTR-/-, the latter lacking expression of mCFTR in the lung. However, a small but significant decrease in bacterial killing was observed in lungs of homozygote SP-C-hCFTR+/+ mice. Lung pathology in both WT and SP-C-hCFTR+/+ mice was marked by neutrophilic inflammation and bacterial invasion of perivascular and subepithelial compartments. Bacteria were associated primarily with leukocytes and were not associated with alveolar type II or bronchiolar epithelial cells, the cellular sites of SP-C-hCFTR+/+ transgene expression. The results indicate that there is no direct correlation between levels of CFTR expression and bacterial clearance or association of bacteria with epithelial cells in vivo.


Protein phosphatases in cell division: how vital are they?
In contrast to the wealth of information on cellular function of protein kinases, many of which are known to be the products of proto-oncogenes, little is known about how protein dephosphorylation is involved in growth control of normal and malignant cells. In the present study, roles of protein phosphatases in cell division cycle control were examined by molecular genetic approaches using a lower eukaryote, the fission yeast Schizosaccharomyces pombe. Nine protein phosphatase genes have been so far identified and characterized in this organism. Each of two (dis2+, sds21+, and ppa1+, ppa2+) gene products is highly similar to mammalian type 1 and 2A ser/thr phosphatases, respectively. The ppx1+ product is an intermediate of type 1 and 2A, while the ppb1+ product is similar to Ca(2+)-dependent type 2B. At least two protein tyrosine phosphatase genes (pyp1+ and pyp2+) exist. The cdc25 protein is now established to be a tyrosine phosphatase that activates cdc2 kinase. Some of these phosphatase genes are interrelated but have distinct, essential functions in cell cycle control. Missense mutations, deletions or high dosage expression of these phosphatase genes affect entry into and exit from mitosis, mitotic chromosome disjunction, cell size and cell shape. They seem to interact with the main regulators of mitosis, cdc2, cdc13/cyclin, cdc25 and weel, or with mitotic structural components, such as condensed chromosomes or the spindle apparatus. We show that the product of an essential gene, sds22+, is an important, positive factor in controlling the expression and modulating the activity of dis2 phosphatase.


Relativistic ultrafast electron diffraction at high repetition rates.
The ability to resolve the dynamics of matter on its native temporal and spatial scales constitutes a key challenge and convergent theme across chemistry, biology, and materials science. The last couple of decades have witnessed ultrafast electron diffraction (UED) emerge as one of the forefront techniques with the sensitivity to resolve atomic motions. Increasingly sophisticated UED instruments are being developed that are aimed at increasing the beam brightness in order to observe structural signatures, but so far they have been limited to low average current beams. Here, we present the technical design and capabilities of the HiRES (High Repetition-rate Electron Scattering) instrument, which blends relativistic electrons and high repetition rates to achieve orders of magnitude improvement in average beam current compared to the existing state-of-the-art instruments. The setup utilizes a novel electron source to deliver femtosecond duration electron pulses at up to MHz repetition rates for UED experiments. Instrument response function of sub-500 fs is demonstrated with < 100 fs time resolution targeted in future. We provide example cases of diffraction measurements on solid-state and gas-phase samples, including both micro- and nanodiffraction (featuring 100 nm beam size) modes, which showcase the potential of the instrument for novel UED experiments.


Central neuroinflammation in Covid-19: a systematic review of 182 cases with encephalitis, acute disseminated encephalomyelitis, and necrotizing encephalopathies.
Growing evidence demonstrates the association of encephalitis, meningoencephalitis or encephalomyelitis, with SARS-CoV-2 infection. This study aims to determine the profile and possible mechanisms behind CNS inflammatory diseases in the context of Covid-19. We conducted a systematic review of case reports on Covid-19-related encephalitis, meningoencephalitis, acute necrotizing encephalitis, and acute disseminated encephalomyelitis in adults, published before January 2021. A total of 182 cases (encephalitis = 109, meningoencephalitis = 26, acute disseminated encephalomyelitis = 35, acute necrotizing (hemorrhagic) encephalitis = 12) were included. While cerebrospinal fluid (CSF) pleocytosis and increased protein level was present in less than 50%, magnetic resonance imaging (MRI) and electroencephalogram (EEG) were abnormal in 78 and 93.2% of all cases, respectively. Viral particles were detected in cerebrospinal fluid of only 13 patients and autoantibodies were present in seven patients. All patients presented with altered mental status, either in the form of impaired consciousness or psychological/cognitive decline. Seizure, cranial nerve signs, motor, and reflex abnormalities were among associated symptoms. Covid-19-associated encephalitis presents with a distinctive profile requiring thorough diagnosis and thereby a comprehensive knowledge of the disease. The clinical profile of brain inflammation in Covid-19 exhibits majority of abnormal imaging and electroencephalography findings with mild/moderate pleocytosis or proteinorrhachia as prevalent as normal cerebrospinal fluid (CSF). Oligoclonal bands and autoantibody assessments are useful in further evaluating neuro-covid patients, as supported by our pooled evidence. Despite the possibility that direct viral invasion cannot be easily estimated, it is still more likely that immune-mediated or autoimmune reactions play a more important role in SARS-CoV-2 neuroinflammation.


Midlife women's attributions for their sexual response changes.
This study focused on the sexual response changes of 280 mostly White, married, highly educated midlife women and on the attributions they made for these changes. In a U.S. sample of women participating in the Midlife Women's Health Survey (MWHS), women whose sexual response had changed in the past year (40%) reported more decrements than increases in sexual response. When asked how they accounted for these changes, women referred most often to the physical and emotional changes of menopause and to life circumstances, and less often to their relationships with their partners. The attributions showed a distinct pattern: Most of the decrements were explained by physical events related to menopause, whereas most of the increases were explained by life circumstances. These findings are discussed in terms of a need for studying women's sexuality from a biopsychosocial perspective.


[Specific safety and immunogenicity of a subunit vaccine against hepatitis B].
The results of trials of a subunit vaccine against hepatitis B in volunteers are presented. The active substance of the vaccine was HBsAg isolated from the plasma of asymptomatic antigen carriers. The preparation under study is highly immunogenic, shows poor reactogenicity, and safety in use.


[Transcription Factor NRF2 in Endothelial Functions].
The transcription factor NRF2 is a major regulator of cell antioxidant defense. NRF2 is activated by various stimuli, such as oxidants and electrophiles, to induce transcription of a number of genes whose products are involved in xenobiotic metabolism and contribute to the reduction of oxidative stress. NRF2 is one of the key transcription factors that ensure the endothelial cell function. The endothelium is a cell layer that lines the lumens of blood vessels and performs various homeostatic functions, controlling migration of leukocytes, regulating thrombosis and vascular tone, and playing a role in angiogenesis. Endothelial dysfunction is often accompanied by inflammation and oxidative stress, which may lead to cell aging and cell death by apoptosis, necrosis, or ferroptosis. Endothelial dysfunction contributes to the development of diabetes and common cardiovascular disorders, such as hypertension and atherosclerosis. Many pathophysiological processes in the endothelium, including senile changes, are associated with decreased NRF2 activity, leading to inflammatory activation and decreasing activity of the cell antioxidant defense systems. Activation of the NRF2 signaling pathway generally contributes to the resolution of inflammation and oxidative stress. The review focuses on the role that NRF2 plays in basic functions of the endothelium in normal and pathological conditions. Advantages and disadvantages of NRF2 activation as a way to prevent and treat cardiovascular diseases are discussed additionally.


Exploration of lagged associations using longitudinal data.
Several statistical approaches for the analysis of longitudinal data require that models be correctly specified for the association between a current outcome and the full history of past outcomes and time-dependent exposures. It is empirically challenging to determine the specific aspects of the outcome and/or exposure history that are predictive of a current outcome because the potential number of variables representing the history can be quite large. The purpose of this article is to outline statistical methods that can characterize lagged effects and to provide a structured approach for data analysis with the goal of appropriate model development. One of the main contributions of the article is to emphasize the possibility that in practice transition models may frequently require more than simple additive and linear models for the predictors representing the history of the outcome and covariate processes. We illustrate the concepts using an example from anemia treatment for dialysis patients and show how linear models can be specified with flexible dependence on exposure and/or outcome histories.


A comparison of persons with early-versus late-onset panic attacks.
Although some evidence suggests a bimodal age at onset of panic attacks, the literature comparing subjects with early versus late onset is limited. Previous work suggests that people with late-onset panic attacks may have fewer panic symptoms and exhibit less avoidance. This study sought to compare late-onset panic attacks and early-onset panic attacks with regard to (I) comorbidity, (2) health care utilization, and (3) illness behaviors and coping. This community-based study involved interviewing randomly selected adults for the presence of DSM-III-R panic attacks. If panic attacks were confirmed, subjects were asked questions concerning panic characteristics, psychiatric comorbidity, symptom perceptions, illness attitudes, coping, and family characteristics. Subjects reporting early-onset panic (panic onset < 50 years of age) were compared with those reporting late onset (onset > or = 50 years of age). Significant univariate analyses were controlled for differences in age, panic duration, and socioeconomic status by using analysis of covariance and logistic regression. Subjects with late-onset panic attacks (N = 9) utilized the mental health sector less, but were more likely to present to family physicians for their worst panic. Patients with late-onset panic felt that choking and numbness more strongly disrupted function, but felt less strongly that either depersonalization or sweating disrupted function. Subjects with late-onset had fewer comorbid conditions and lower Symptom Checklist-90 scores. Late-onset subjects also had less hypochondriasis and thanatophobia while coping less through avoidance or wishful thinking. Late-onset panic attacks are associated with less mental health utilization, lower levels of comorbidity, less hypochondriasis, and a greater number of positive coping behaviors.


Kindling-like stimulus patterns induce epileptiform discharges in the guinea pig in vitro hippocampus.
In the guinea pig in vitro hippocampal slice preparation, we have demonstrated that the repeated tetanic stimulation of the Schaffer collateral-commissural input to CA1 pyramidal neurones produces a progressive increase in the amplitude and duration of postsynaptic potentials, and stimulus-induced and spontaneous paroxysmal depolarization shifts (PDSs). Both the enhancement of synaptic transmission and the genesis of PDSs were reversibly blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-2-amino-5-phosphonovalerate (APV). These results provide evidence that progressive, stimulation-induced long-term potentiation may serve as the trigger for kindling-induced epileptogenesis, and this process is dependent on the repeated activation of an APV-sensitive receptor.


[Lead poisoning. A case of polyneuropathy in an infant].
A case of a four month-old child diagnosed of lead polyneuropathy is reported. He has been under mechanical ventilation without significant problems for eleven months which has allowed respiratory neuromuscular function to recover. Skeletal muscle function is undergoing an awkward improvement. According to this case, in cases of child polyneuropathy, chance that the child might have lead poisoning should be considered. Finally it should be noted that supportive measures, such as mechanical ventilation and muscle physiotherapy, have a very important role in the recovery.


Positron Emission Tomography (PET) in Oncology.
Since its introduction in the early nineties as a promising functional imaging technique in the management of neoplastic disorders, FDG-PET, and subsequently FDG-PET/CT, has become a cornerstone in several oncologic procedures such as tumor staging and restaging, treatment efficacy assessment during or after treatment end and radiotherapy planning. Moreover, the continuous technological progress of image generation and the introduction of sophisticated software to use PET scan as a biomarker paved the way to calculate new prognostic markers such as the metabolic tumor volume (MTV) and the total amount of tumor glycolysis (TLG). FDG-PET/CT proved more sensitive than contrast-enhanced CT scan in staging of several type of lymphoma or in detecting widespread tumor dissemination in several solid cancers, such as breast, lung, colon, ovary and head and neck carcinoma. As a consequence the stage of patients was upgraded, with a change of treatment in 10%-15% of them. One of the most evident advantages of FDG-PET was its ability to detect, very early during treatment, significant changes in glucose metabolism or even complete shutoff of the neoplastic cell metabolism as a surrogate of tumor chemosensitivity assessment. This could enable clinicians to detect much earlier the effectiveness of a given antineoplastic treatment, as compared to the traditional radiological detection of tumor shrinkage, which usually takes time and occurs much later.


Engagement for Alcohol Escalates in the 5-Choice Serial Reaction Time Task After Intermittent Access.
Uncontrollable binge drinking is becoming an increasingly prevalent issue in our society. This is a factor that plays a role in the development of alcohol use disorder (AUD). AUD impacts 15 million Americans annually, with approximately 88,000 dying from alcohol related deaths. There are several aspects of AUD that encourage a strong dependence on alcohol. Impulsivity, motivation, and attention are the primary behavioral facets we contribute to AUD. Many past studies have used the 5-Choice Serial Reaction Time Task (5-Choice) to analyze these types of behaviors using sugar as the reward. We have recently published a study where alcohol was used as a reward in the 5-Choice. 48 mice were trained to respond for alcohol in the 5-Choice, and the analyses for these animals were originally categorized by their alcohol preference and consumption. Upon looking at the data, we became more interested in a new way to classify these mice into groups. High engaged (HE) and low engaged (LE) mice were classified based on their number of correct responses in the last five late-stage sessions. During early-stage training, mice began to separate themselves into two groups based on their interaction with the task. The high-engaged (HE) mice were much more engaged with the task by having a high number of trials and correct responses, as well as a much lower percentage of omissions. The low engaged (LE) mice were not as engaged, this was apparent because of their lower number of trials and correct responses. They also had a much higher percentage of omissions in comparison to HE mice. LE mice presented no significant changes in late-stage training, while HE mice began responding and engaging more. These mice went through a period of intermittent access (IA), where they were allowed to drink alcohol in their cage for 3 weeks. After intermittent access, LE mice increased their responding which suggests an increase in motivation for alcohol as a reward. Engagement analysis presents two clearly different groups, one being motivated to work for alcohol and the other not wanting to work for this reward. These two distinct phenotypes in the 5-Choice could be used to model alcohol motivated behavior, which could help us further understand AUD.


Differential Redox State Contributes to Sex Disparities in the Response to Influenza Virus Infection in Male and Female Mice.
Influenza virus replicates intracellularly exploiting several pathways involved in the regulation of host responses. The outcome and the severity of the infection are thus strongly conditioned by multiple host factors, including age, sex, metabolic, and redox conditions of the target cells. Hormones are also important determinants of host immune responses to influenza and are recently proposed in the prophylaxis and treatment. This study shows that female mice are less susceptible than males to mouse-adapted influenza virus (A/PR8/H1N1). Compared with males, PR8-infected females display higher survival rate (+36%), milder clinical disease, and less weight loss. They also have milder histopathological signs, especially free alveolar area is higher than that in males, even if pro-inflammatory cytokine production shows slight differences between sexes; hormone levels, moreover, do not vary significantly with infection in our model. Importantly, viral loads (both in terms of viral M1 RNA copies and tissue culture infectious dose 50%) are lower in PR8-infected females. An analysis of the mechanisms contributing to sex disparities observed during infection reveals that the female animals have higher total antioxidant power in serum and their lungs are characterized by increase in (i) the content and biosynthesis of glutathione, (ii) the expression and activity of antioxidant enzymes (peroxiredoxin 1, catalase, and glutathione peroxidase), and (iii) the expression of the anti-apoptotic protein Bcl-2. By contrast, infected males are characterized by high expression of NADPH oxidase 4 oxidase and phosphorylation of p38 MAPK, both enzymes promoting viral replication. All these factors are critical for cell homeostasis and susceptibility to infection. Reappraisal of the importance of the host cell redox state and sex-related effects may be useful in the attempt to develop more tailored therapeutic interventions in the fight against influenza.


Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus.
1. gamma-Aminobutyric acidA (GABAA) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABAA and late, GABAB receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) and were not changed by the GABAB receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35,348; 0.1-1.0 mM). CGP 35,348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABAA receptor-mediated population IPSPs (GABAA, fast pIPSPs) and that late field potentials are GABAB receptor-mediated population IPSPs (GABAB, late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration [( Cl-]o) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35,348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABAA current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4-aminopyridine (50-100 microM), DNQX and APV long-lasting depolarizing GABAA receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)


Regional differences in acute corticosterone-induced dendritic remodeling in the rat brain and their behavioral consequences.
Glucocorticoid released by stressful stimuli elicits various stress responses. Acute treatment with a single dose of corticosterone (CORT; predominant glucocorticoid of rats) alone has previously been shown to trigger anxiety behavior and robust dendritic hypertrophy of neurons in the basolateral amygdala (BLA). Neurons in the medial prefrontal cortex (mPFC) are also known to be highly sensitive to stress and regulate anxiety-like behaviors. Nevertheless, we know less about acute CORT-induced structural changes of other brain regions and their behavioral outcomes. In addition, the temporal profile of acute CORT effects remains to be examined. The current study investigates time course changes of dendritic architectures in the stress vulnerable brain areas, the BLA and mPFC, and their behavioral consequences after acute treatment with a single dose of CORT. Acute CORT treatment produced delayed onset of dendritic remodeling in the opposite direction in the BLA and mPFC with different time courses. Acute CORT induced dendritic hypertrophy of BLA spiny neurons, which was paralleled by heightened anxiety, both peaked 12 days after the treatment. Meanwhile, CORT-induced dendritic atrophy of mPFC pyramidal neurons peaked on day 6, concomitantly with impaired working memory. Both changed dendritic morphologies and altered behavioral outcomes were fully recovered. Our results suggest that stress-induced heightened anxiety appears to be a functional consequence of dendritic remodeling of BLA neurons but not that of mPFC. Instead, stress-induced dendritic atrophy of mPFC neurons is relevant to working memory deficit. Therefore, structural changes in the BLA and the mPFC might be specifically associated with distinct behavioral symptoms observed in stress-related mental disorders. Remarkably, stress-induced dendritic remodeling in the BLA as well as mPFC is readily reversible. The related behavioral outcomes also follow the similar time course in a reversible manner. Therefore, further studies on the cellular mechanism for the plasticity of dendrites architecture might provide new insight into the etiological factors for stress-related mental illness such as posttraumatic stress disorder (PTSD).


Alcohol consumption during pregnancy and perinatal results: a cohort study.
Alcohol consumption during pregnancy is a significant social problem that may be associated with adverse perinatal outcomes. The aim of this study was to describe alcohol consumption during pregnancy and to study its association with low birth weight, newborns small for gestational age and preterm birth. Nested cohort study, in the city of Ribeirão Preto, São Paulo, Brazil. 1,370 women and their newborns were evaluated. A standardized questionnaire on health and lifestyle habits was applied to the mothers. Anthropometry was performed on the newborns. Alcohol consumption was defined as low, moderate or high, as defined by the World Health Organization. Adjusted logistic regression analysis was used. 23% of the women consumed alcohol during pregnancy. Consumption mainly occurred in the first trimester (14.8%) and decreased as the pregnancy progressed. The median alcohol intake was 3.89 g (interquartile range, IQR = 8 g) per day. In the unadjusted analysis, alcohol consumption increased the risk of low birth weight almost twofold (odds ratio, OR 1.91; 95% confidence interval, CI: 1.25-2.92). The risk was lower in the adjusted analysis (OR 1.62; 95% CI: 1.03-2.54). Alcohol consumption did not show associations with small for gestational age or preterm birth. There was greater risk of low birth weight and newborns small for gestational age and preterm birth among mothers who were both smokers and drinkers. The alcohol consumption rate during pregnancy was 23% and was independently associated with low birth weight, but there was no risk of newborns small for gestational age or preterm birth.


Adhesion GPCRs in glioblastoma revisited.
Glioblastoma is a devastating brain malignancy that has remained intractable to modern cancer treatments. Ravn-Boess et al.1 have discovered that the adhesion G protein-coupled receptor CD97/ADGRE5 contributes to glioblastogenesis and makes for an excellent molecular surface marker flagging the tumor cells.


[DNA chip technology].
DNA chip technology has greatly evolved over the last decade and, associated with complete genome sequencing, is in the process of introducing a revolution into biological research. It is providing new and unique tools for studying emerging diseases outbreaks and epidemics. Nevertheless, microbiological surveillance, medical diagnosis, and field work involve a number of difficulties for which these new techniques have not yet been validated. Currently available chips are still limited in their application, but offer a powerful and economical alternative to former methods and will undoubtedly offer a range of unexplored applications in coming years.


Porcelain repair materials. Council on Dental Materials, Instruments and Equipment.
Porcelain repair materials, when properly chosen and used, provide some bond strength in bonding to porcelain. The bond strength is decreased by thermocycling and long-term storage in water. Currently available products are affected differently by these conditions. Surface roughening by rotary instruments and chemical etching by hydrofluoric acid or APF enhances the bond strength. The long-term clinical performance of the porcelain repair materials is not well documented. The council is preparing guidelines to evaluate these materials under the Acceptance Programs of the council. These guidelines will include requiring information on the laboratory and chemical data on these products to demonstrate their safety and efficacy.


Growth-promoting effect of Rh(D) antibody on human pancreatic islet cells.
Hyperinsulinism with islet cell hyperplasia is a frequent complication, of unknown cause, in hemolytic disease of the newborn, occurring in Rh(D)-positive infants of Rh-isoimmunized Rh(D)-negative mothers, but not in infants with other hemolytic disorders. We investigated the possibility that trans-placentally acquired anti-D Ig is the cause of both conditions. Monolayer cultures of human islet cells were exposed to sera from Rh-isoimmunized mothers and newborns, where jaundice, hyperinsulinism, and hypoglycemia in the infant had ensued. Parallel cultures with anti-D, specific anti-D monoclonal antibodies, normal human Ig (15 microg/ml), and serum controls were also undertaken. Islet cell proliferation was determined by [3H]thymidine incorporation. Insulin storage and chronic and acute insulin secretion to glucose were analyzed by RIA. Rh(D) surface antigen expression was determined on islet cells by flow cytometric analysis. Islet cell proliferation and insulin secretion were significantly greater in coculture with test sera (P < 0.01; n = 8) and with anti-D (P < 0.001; n = 8), compared with either controls or Ig. After 8 d of growth, the static incubation experiment showed a 3.5-fold response to glucose stimulus in all sera. Rh(D) antigen expression was detected on the islet cell surface by flow cytometry, and islet cell morphology was normal. Colocalization of the proliferation marker Ki67 with insulin by immunofluorescent staining further indicated that Rh(D) antibody promoted islet growth. The anti-Rh(D) islet cell proliferative effect generates neonatal hyperinsulinism in Rh isoimmunization. Anti-Rh(D) may have application for islet cell proliferation in diabetes mellitus treatment for Rh(D)-positive subjects. Further analysis is required.


Assessing functioning and self-care abilities in Alzheimer disease research.
Functional performance is a critical outcome to examine in dementia. The authors review some of the limitations of current research on functional performance and identify a conceptual framework for outcomes research. When considering conceptual frameworks to apply to functional assessment for outcomes research, five broad issues emerge: variability in definitions, an assumed equality between functional performance and capacity, measurement of global task abilities but not abilities for task components, lack of a contextual perspective, and use of a physical disability framework that excludes cognitive disability. When selecting assessment methods, researchers also must consider the implications of informant-based instruments and performance-based instruments. The authors also discuss a conceptual framework for evaluating current functional performance assessment instruments.


LRRK2 A419V is not associated with Parkinson's disease in different Chinese populations.
It has been suggested that a common LRRK2 polymorphic variant (A419V (rs34594498 C >T)) may be a risk factor among Asians (especially in Taiwan). In this study, we examined this variant in a larger and independent Taiwan cohort. We found the frequency of the variant (A419V) to be very rare in our Taiwan PD and controls (?0.6%). Further studies were conducted in two other Chinese populations (Singapore and China), comprising of a total of 3004 subjects including 1517 PD patients and 1487 control subjects. However, our multi-center Chinese study revealed that the frequency of the variant was rare (?0.4%) and was not associated with risk of PD, suggesting that the variant is not a major risk factor for PD among Chinese, at least in our study population.


Primary Ectopic Ethmoidal Craniopharyngioma.
Craniopharyngiomas are benign but aggressive epithelial tumors usually originating in the anterior lobe of the pituitary gland from squamous remnants of an incompletely involuted craniopharingeal duct developing from the Rathke pouch. To the authors' knowledge only 1 patient of a primary isolated ethmoidal craniopharyngioma has been reported in the literature.The authors report the case of a 17-year-old boy with a primary extracranial ethmoidal craniopharyngioma. An endoscopic endonasal approach was employed to resect the tumor. After 2 years of clinical and radiological follow-up no recurrence of disease was observed.Primary ethmoidal craniopharyngiomas are rare entities and biopsy is necessary for diagnosis. However, a preoperative assessment by means of nasal endoscopy, computed tomography scan, and enhanced magnetic resonance imaging is mandatory to better evaluate the extension and characteristics of the tumor. The endoscopic endonasal technique is a safe and effective approach for the treatment of these lesions.


POPing the fire into the pyrin?
Initiation of an inflammatory response requires the co-ordinated participation of proteins within a scaffold in the cytosol of responding cells. The scaffold proteins contain members of a newly discovered family of pyrin-domain adaptor proteins that regulate complex assembly for initiation of nuclear factor kappaB and interleukin-1beta signalling. A paper in this issue of the Biochemical Journal by Stehlik et al. identifies a new member of the pyrin family that may control signalling by sequestering pro-inflammatory components, shedding light on the origin of human inflammatory disorders.


Application of the Adaptive Validation Substudy Design to Colorectal Cancer Recurrence.
Among men and women diagnosed with colorectal cancer (CRC), 20-50% will develop a cancer recurrence. Cancer recurrences are not routinely captured by most population-based registries; however, linkage across Danish registries allows for the development of predictive models to detect recurrence. Successful application of such models in population-based settings requires validation against a gold standard to ensure the accuracy of recurrence identification. We apply a recently developed validation study design for prospectively collected validation data to validate predicted CRC recurrences against gold standard diagnoses from medical records in an actively followed cohort of CRC patients in Denmark. We use a Bayesian monitoring framework, traditionally used in clinical trials, to iteratively update classification parameters (positive and negative predictive values, and sensitivity and specificity) in an adaptive validation substudy design. This design allows determination of the sample size necessary to estimate the corresponding parameters and to identify when validation efforts can cease based on predefined criteria for parameter values and levels of precision. Among 355 men and women diagnosed with CRC in Denmark and actively followed semi-annually, there were 63 recurrences diagnosed by active follow-up and 70 recurrences identified by a predictive algorithm. The adaptive validation design met stopping criteria for the classification parameters after 120 patients had their recurrence information validated. This stopping point yielded parameter estimates for the classification parameters similar to those obtained when the entire cohort was validated, with 66% less patients needed for the validation study. In this proof of concept application of the adaptive validation study design for outcome misclassification, we demonstrated the ability of the method to accurately determine when sufficient validation data have been collected. This method serves as a novel validation substudy design for prospectively collected data with simultaneous implementation of a validation study.


Impaired conscious and preserved unconscious inhibitory processing in recent onset schizophrenia.
Impairments in inhibitory function have been found in studies of cognition in schizophrenia. These have been linked to a failure to adequately maintain the task demands in working memory. As response inhibition is known to occur in both voluntary and involuntary processes, an important question is whether both aspects of response inhibition are specifically impaired in people with schizophrenia. The subjects were 33 patients presenting with a first episode of psychosis (27 with schizophrenia and six with schizo-affective disorder) and 24 healthy controls. We administered two motor response tasks: voluntary response inhibition was indexed by the stop-signal task and involuntary response inhibition by the masked priming task. We also administered neuropsychological measures of IQ and executive function to explore their associations with response inhibition. Patients with schizophrenia compared to healthy controls showed significantly increased duration of the voluntary response inhibition process, as indexed by the stop-signal reaction time (SSRT). By contrast, there were no group differences on the pattern of priming on the masked priming task, indicative of intact involuntary response inhibition. Neuropsychological measures revealed that voluntary response inhibition is not necessarily dependent on working memory. These data provide evidence for a specific impairment of voluntary response inhibition in schizophrenia.


Characterization of peripheral blood acetylcholine receptor-binding B cells in experimental myasthenia gravis.
In myasthenia gravis (MG), the neuromuscular transmission is impaired by antibodies (Abs) specific for muscle acetylcholine receptor (AChR). Anti-AChR Abs can be detected in the serum of MG patients, although their levels do not correlate with disease severity. In this study, we developed a flow cytometric assay for the detection of peripheral blood AChR-specific B cells to characterize B cell phenotypes associated with experimental autoimmune myasthenia gravis (EAMG). Alexa-conjugated AChR was used as a probe for AChR-specific B cells (B220+Ig+). Mice with EAMG had significantly elevated frequencies of AChR-specific IgG2+ and IgM+ B cells. While the frequencies of IgG2+ B cells and plasma anti-AChR IgG2 levels significantly correlated with the clinical grades of EAMG, the frequencies of IgM+ B cells and plasma anti-AChR IgM levels did not. These results indicate that the frequency of AChR-specific and IgG1+ (mouse IgG2 equivalent) peripheral blood B cells and anti-AChR IgG1 levels could be potential biomarkers for MG disease severity.


[Role of pulsed Doppler of the inferior thyroid artery in patients without hyperthyroidism].
The authors present their statistical results in terms of maximum velocity and resistive Index of the inferior thyroid artery in a group of 200 patients, all with different diseases of the gland, but without hyperthyroidism. Measurements were taken in the first tract of the inferior thyroid artery, deep and posterior to the common carotid, without encountering any significant difficulties in 83% of cases, the determinations taking less than one minute; in some patients stretching or rotation of the neck was necessary in order to obtain a good result. The maximum systolic velocities were in agreement with those reported in the literature, but statistical analysis showed a significant correlation between systolic peak and certain groups or types of disease and, albeit less reliably, between the Resistive Index and type of disease. The section of the individual vessels showed no statistically significant variations. The results indicate a possible correlation between peak systolic velocity and Reistive Index in patients without hyperthyroidism, and therefore it may now be useful to study the relationship between these two parameters also in patients with normal serum levels of thyroid hormones.


[Body condition and metabolic stability as the basis for high milk yield and undisturbed fertility in dairy cows--a contribution for deduction of reference values].
The target of this study was to describe the interactions between body condition and various descriptors of yield and fertility. It was aimed to identify an optimal conditional range to be used in herd management which combines high milk yield with acceptable fertility traits and general health. For this purpose, backfat thickness was measured by ultrasound at 46111 dairy cows on 78 different farms and was subsequently related to production variables. Negative energy balance is getting more intense and prolonged with increasing milk yield. However a conditional nadir below 10 mm leads to decreased milk production. To reach a high production level without an increasing incidence of health disorders, conditional nadir should not decline below 13 mm backfat thickness on herd average. Lower value only lead to negligibly higher milk yield but cause a distinctively higher risk of fertility problems and culling. High herd yields do not have to be at expense of reproduction performance and can be achieved without extreme body condition losses. An efficient herd management can offset depression in fertility, which commonly is combined with increasing milk yield. A standard curve for backfat thickness throughout lactation is suggested to be used in dairy herd management.


Seasonality of helminth infection in wild red deer varies between individuals and between parasite taxa.
Parasitism in wild mammals can vary according to myriad intrinsic and extrinsic factors, many of which vary seasonally. However, seasonal variation in parasitism is rarely studied using repeated samples from known individuals. Here we used a wild population of individually recognized red deer (Cervus elaphus) on the Isle of Rum to quantify seasonality and intrinsic factors affecting gastrointestinal helminth parasitism over the course of a year. We collected 1020 non-invasive faecal samples from 328 known individuals which we then analysed for propagules of three helminth taxa: strongyle nematodes, the common liver fluke Fasciola hepatica and the tissue nematode Elaphostrongylus cervi. Zero-inflated Poisson models were used to investigate how season, age and sex were associated with parasite prevalence and count intensity, while Poisson models were used to quantify individual repeatability within and between sampling seasons. Parasite intensity and prevalence varied according to all investigated factors, with opposing seasonality, age profiles and sex biases between parasite taxa. Repeatability was moderate, decreased between seasons and varied between parasites; both F. hepatica and E. cervi showed significant between-season repeatability, while strongyle nematode counts were only repeatable within-season and showed no repeatability within individuals across the year.


Respiratory diseases in the first year of life in children born to HIV-1-infected women.
Our objective was to describe the respiratory complications, clinical findings, and chest radiographic changes in the first year of life in infected and uninfected children born to HIV-1-infected women. We prospectively followed a cohort of 600 infants born to HIV-1-infected women from birth to 12 months in a multicenter study. Of these, 93 infants (15.5%) were HIV-1-infected, 463 were uninfected, and 44 were of unknown status prior to death or loss to follow-up. The cumulative incidence ( +/- SE) of an initial pneumonia episode at 12 months was 24.1 +/- 4.7% in HIV-1-infected children compared to 1.4 +/- 0.6% in HIV-1-uninfected children (P < 0.001). The rate of Pneumocystis carinii pneumonia (PCP) was 9.5 per 100 child-years. The HIV-1 RNA load was not higher in the group that developed pneumonia in the first year vs. those who did not. Children who developed lower respiratory tract infections or PCP had increased rates of decline of CD4 cell counts during the first 6 months of life. Lower maternal CD4 cell counts were associated with higher rates of pneumonia, and upper and lower respiratory tract infections. The rates of upper respiratory tract infection and bronchiolitis/reactive airway disease in infected children were not significantly different than in uninfected children. At 12 months, significantly more HIV-1-infected than uninfected children had tachypnea and chest radiographs with nodular and reticular densities. There was no relationship between cytomegalovirus infection in the first year of life and radiographic changes or occurrences of pneumonia. In conclusion, despite a low incidence of PCP, rates of pneumonia remain high in HIV-infected children in the first year of life. The incidence of pneumonia in uninfected infants born to HIV-1-infected mothers is low. Chest X-ray abnormalities and tachypnea suggest that subacute disease is present in infected infants. Further follow-up is warranted to determine its nature.


[Determination of boric acid and silicic acid in mineral water by nonsuppressed ion chromatography].
Boron and silicon are widely distributed in nature; in water, these compounds typically present in the forms of boric acid and silicic acid, respectively. The maximum allowable levels of silicic acid and boric acid in water are stipulated in relevant national and industry standards, such as GB 8538-2022. Quality changes in water, which are of great significance in water-quality evaluations, can be understood in terms of its silicic acid and boric acid contents. Boric acid content is usually determined by ion exclusion chromatography, whereas silicic acid content is usually determined by postcolumn derivatization. Therefore, traditional methods cannot achieve the simultaneous determination of silicic acid and boric acid contents in water. Modern ion chromatography has been widely used in the detection of ionic compounds, such as anions, cations, organic acids, organic amines, amino acids, and sugars. Boric (pKa=9.24) and silicic (pKa=9.77) acids are weak acids that dissociate into ionic states under alkaline conditions. Although these compounds cannot be tested using suppressed ion chromatography, they can be retained on ion chromatography columns. In this study, a method based on nonsuppressed conductance detection was established for the simultaneous determination of boric acid and silicic acid in water. The contents of boric acid and silicic acid were detected by nonsuppressed ion chromatography using a Dionex IonPacTM AS20 analytical column. The chromatographic conditions were as follows: flow rate, 1.0 mL/min; column temperature, 30 ℃; eluent, 6 mmol/L sodium hydroxide solution and 60 mmol/L mannitol; and sample injection volume, 50 μL. The effective separation of silicic acid and boric acid was achieved within 8 min. SiO32- and boric acid demonstrated good linear relationships in the concentration ranges of 0.25-100 and 0.5-100 mg/L (correlation coefficients, 0.9999), respectively. The method detection (MDL) and quantification (MQL) limits were 0.078 and 0.26 mg/L for SiO32-, and the MDL and MQL limits were 0.18 and 0.60 mg/L for boric acid. The average recoveries of boric acid and SiO32- (n=6) were 97.3%-105.3%. Moreover, the relative standard deviations were less than 0.9% for boric acid at four spiked levels and less than 0.30% for SiO32- at three spiked levels. Thus, the method meets detection requirements. The pretreatment method is very simple, and the sample can be directly injected through a 0.22 μm water filtration membrane and into the column. The boric acid and silicic acid contents in nine mineral drinking water samples were determined under the optimized analytical conditions. Boric acid was not detected in these nine samples, but silicic acid was detected in six samples. The silicic acid contents detected were between 18.70 and 62.08 mg/L, which was consistent with the concentration ranges marked on the manufacturers' packaging. The proposed method can be used for the determination of boric acid and silicic acid in mineral drinking water and laboratory water, and provides a reference for the simultaneous detection of boric acid and silicic acid in ultrapure water used in the semiconductor industry.


The emerging role of CD30 and p53 as novel targets for therapy in anaplastic large cell lymphoma.
ALK+ anaplastic large cell lymphoma (ALCL). frequently carries the t(2;5).(p23;q35). resulting in expression of NPM-ALK oncogenic kinase, which is capable of activating multiple oncogenic pathways. ALK+ ALCL is also characterized by overexpression of CD30 receptor, a member of the tumor necrosis factor (TNF). receptor superfamily, which has been targeted for therapy using conjugated anti-CD30 antibodies with clinical success. Also, the tumor suppressor p53 is frequently non-mutated in ALK+ ALCL allowing for therapeutic modulation of p53 reactivation in this lymphoma type. Therefore, this review is focused on the role of CD30 receptor and p53 as novel targets for therapy in ALK+ ALCL, and also provides an update on their potential involvement in ALK+ ALCL pathogenesis.


Emotion network density is a potential clinical marker for anxiety and depression: Comparison of ecological momentary assessment and daily diary.
Using two intensive longitudinal data sets with different timescales (90 minutes, daily), we examined emotion network density, a metric of emotional inflexibility, as a predictor of clinical-level anxiety and depression. Mobile-based intensive longitudinal assessments. 119 participants (61 anxious and depressed, 58 healthy controls) completed ecological momentary assessment (EMA) to rate a variety of negative (NE) and positive emotions (PE) 9 times per day for 8 days using a mobile phone application. 169 participants (97 anxious and depressed and 72 healthy controls) completed an online daily diary on their NE and PE for 50 days. Multilevel vector autoregressive models were run to compute NE and PE network densities in each data set. In the EMA data set, both NE and PE network densities significantly predicted participants' diagnostic status above and beyond demographics and the mean and standard deviation of NE and PE. Greater NE network density and lower PE network density were associated with anxiety and depression diagnoses. In the daily diary data set, NE and PE network densities did not significantly predict the diagnostic status. Greater inflexibility of NE and lower inflexibility of PE, indexed by emotion network density, are potential clinical markers of anxiety and depressive disorders when assessed at intra-daily levels as opposed to daily levels. Considering emotion network density, as well as the mean level and variability of emotions in daily life, may contribute to diagnostic prediction of anxiety and depressive disorders. Emotion network density, or the degree to which prior emotions predict and influence current emotions, indicates an inflexible or change-resistant emotion system. Emotional inflexibility or change resistance over a few hours, but not daily, may characterize anxiety and depressive disorders. Inflexible negative emotion systems are associated with anxiety and depressive disorders, whereas inflexible positive emotion systems may indicate psychological health. Considering emotional inflexibility within days may provide additional information beyond demographics and mean level and variability of emotions in daily life for detecting anxiety and depressive disorders.


Finding social need-les in a haystack: ascertaining social needs of Medicare patients recorded in the notes of care managers.
Unmet social needs may impair health and access to health care, and intervening on these holds particular promise in high-risk patient populations, such as those with multiple chronic conditions. Our objective was to identify social needs in a patient population at significant risk-Medicare enrollees with multiple chronic illnesses enrolled in care management services-and measure their prevalence prior to any systematic screening. We partnered with Renova Health, an independent Medicare Chronic Care Management (CCM) provider with patients in 10 states during our study period (January 2017 through August 2020). Our data included over 3,000 Medicare CCM patients, representing nearly 20,000 encounters. We used a dictionary-based natural language processing approach to ascertain the prevalence of six domains of barriers to care (food insecurity, housing instability, utility hardship) and unmet social needs (health care affordability, need for supportive services, transportation) in notes taken during telephonic Medicare CCM patient encounters. Barriers to care, specifically need for supportive services (2.4%) and health care affordability (0.8%), were the most prevalent domains identified. Transportation as a barrier to care came up relatively less frequently in CCM encounters (0.1%). Unmet social needs were identified at a comparatively lower rate, with potential housing instability (0.3%) flagged most followed by potential utility hardship (0.2%) and food insecurity (0.1%). There is substantial untapped opportunity to systematically screen for social determinants of health and unmet social needs in care management.


Electrically evoked wrist extensor muscle fatigue throughout repetitive motion as measured by mechanomyography and near-infrared spectroscopy.
Repetitive electrically-evoked muscle contraction leads to accelerated muscle fatigue. This study assessed electrically-evoked fatiguing muscle with changes to mechanomyography root mean square percentage (%RMS-MMG) and tissue saturation index (%TSI) in extensor carpi radialis. Forty healthy volunteers (n=40) performed repetitive electrical-evoked wrist extension to fatigue and results were analyzed pre- and post-fatigue, i.e. 50% power output (%PO) drop. Responses of %PO, %TSI and %RMS-MMG were correlated while the relationships between %RMS-MMG and %TSI were investigated using linear regression. The %TSI for both groups were negatively correlated with declining %PO as the ability of the muscle to take up oxygen became limited due to fatigued muscle. The %RMS-MMG behaved in two different patterns post-fatigue against declining %PO whereby; (i) group A showed positive correlation (%RMS-MMG decreased) throughout the session and (ii) group B demonstrated negative correlation (%RMS-MMG increased) with declining %PO until the end of the session. Regression analysis showed %TSI was inversely proportional to %RMS-MMG during post-fatigue in group A. Small gradients in both groups suggested that %TSI was not sensitive to the changes in %RMS-MMG and they were mutually exclusive. Most correlation and regression changed significantly post-fatigue indicating that after fatigue, the condition of muscle had changed mechanically and physiologically.


A workforce profile comparison of practising and non-practising midwives in Australia: baseline data from the Midwives and Nurses e-Cohort Study.
Existing workforce data, as an estimate of the current capability of the midwifery workforce to provide midwifery care, is confounded by systematic reporting issues that may overestimate the potential of the existing midwifery workforce. This paper reports the characteristics of qualified Australian midwives who responded to the baseline data collection in the Midwives and Nurses e-Cohort Study and compares those who are currently practising in midwifery with those who are not. Currently practising midwives represented only 52% of those respondents who identified as midwives and the profile of the typical midwife is female, aged over 40 years, Australian, married or in a de facto relationship. She has been registered for over 10 years, educated to postgraduate diploma level and currently works in a clinical midwifery role in a hospital for less than 35 hours per week. Specific deficits in the Australian midwifery workforce namely low numbers of indigenous midwives, independent practitioners and midwives suitably qualified to teach and undertake research in academia are identified. Drawing on the nationally representative e-cohort data, this cross-sectional analysis identifies for the first time the real face of the Australian midwifery workforce and provides an evidence-based foundation for future workforce planning and a methodology for other countries interested in accurately monitoring their actual and potential midwifery workforce.


An Improved Genetic Algorithm for Location Allocation Problem with Grey Theory in Public Health Emergencies.
The demand for emergency medical facilities (EMFs) has witnessed an explosive growth recently due to the COVID-19 pandemic and the rapid spread of the virus. To expedite the location of EMFs and the allocation of patients to these facilities at times of disaster, a location-allocation problem (LAP) model that can help EMFs cope with major public health emergencies was proposed in this study. Given the influence of the number of COVID-19-infected persons on the demand for EMFs, a grey forecasting model was also utilized to predict the accumulative COVID-19 cases during the pandemic and to calculate the demand for EMFs. A serial-number-coded genetic algorithm (SNCGA) was proposed, and dynamic variation was used to accelerate the convergence. This algorithm was programmed using MATLAB, and the emergency medical facility LAP (EMFLAP) model was solved using the simple (standard) genetic algorithm (SGA) and SNCGA. Results show that the EMFLAP plan based on SNCGA consumes 8.34% less time than that based on SGA, and the calculation time of SNCGA is 20.25% shorter than that of SGA. Therefore, SNCGA is proven convenient for processing the model constraint conditions, for naturally describing the available solutions to a problem, for improving the complexity of algorithms, and for reducing the total time consumed by EMFLAP plans. The proposed method can guide emergency management personnel in designing an EMFLAP decision scheme.


[Autoimmune lymphoproliferative syndrome. Update and review].
The autoimmune lymphoproliferative syndrome (ALPS) is an inborn immunity error, which is the result of a heterogeneous group of mutations in the genes that regulate the apoptosis phenomenon. It typically appears in the first years of life. The most common clinical signs are lymphoid expansion with lymphadenopathy, splenomegaly, and hepatomegaly; immune disease with different types of cytopenia, including thrombocytopenia, hemolytic anemia, and lymphoma. The lab abnormalities that facilitate the diagnosis of ALPS include the presence of double negative alpha/beta T cells, high interleukin levels, vitamin B12 in the blood, and FAS-mediated defective apoptosis in the in vitro assay. The treatment of ALPS is focused on three aspects: The treatment of the manifestations of the disease, the prevention/treatment of complications, and the curative treatment (hematopoietic progenitor cell transplantation [HPCT]). The use of immunosuppressive therapy is suggested only for severe complications of lymphoproliferation or concomitant autoimmune manifestations. Splenectomy is not recommended for autoimmune manifestations in patients with ALPS. HPCT is reserved for selected patients. The survival rate to 50 years is estimated at 85% for patients with FAS deficiency.


[Kidney morphology in children with meningococcal infection].
The kidneys of 30 children aged 1 month to 5 years who died of meningococcal infection were studied. Three variants of the kidney damage were distinguished on the basis of morphometric parameters. These variants corresponded to the stages of the infectious-toxic shock. The 1st variant observed in the reversible shock stages was characterized by arteriolar spasm and circulation shunts. The 2nd variant corresponded to initial manifestations of the disseminated vascular coagulation and was characterized by a combination of spasm and paralytic arteriola dilatation with a predominant thrombosis of the juxtamedullar glomeruli. The 3rd variant, the stage of the organ alterations, was followed by development of glomerular thrombotic microangiopathy with tubular epithelial necrosis in the proximal tubules this being the morphological counterpart of the hemolytico-uremic syndrome.


[Study on nurse performance evaluation: obtained results and conclusions - Part III].
In this third part of this study the final part of the analysis, the discussion of the results and the conclusions are presented. The discussion involves the results regarding the specific professional capability of the evaluating nurses and of the respective evaluated nurses; the periodicity of the evaluations, the technics and methodology utilized by nurses in the evaluation process; the instruments used in the performance evaluation process and the reactions to the evaluation. The respective bibliography is presented along with the discussion of the results.


High-pressure Raman spectroscopic study of the ammonia-borane complex. Evidence for the dihydrogen bond.
The Raman spectra of the ammonia-borane complex, NH(3)BH(3), have been investigated as a function of pressure up to 40 kbar. Vibrational modes involving the NH(3) group show negative pressure dependences, supporting the existence of the dihydrogen bond, but the vibrations of the BH(3) group have a positive dependence. Two transitions were observed in the solid phase under pressure, in contrast to the temperature behavior, where a single transition occurs. Factor group splitting occurs for the degenerate vibrations, and this allows the correct assignment of the observed vibrations.


Using a Low-Power Spiking Continuous Time Neuron (SCTN) for Sound Signal Processing.
This work presents a new approach based on a spiking neural network for sound preprocessing and classification. The proposed approach is biologically inspired by the biological neuron's characteristic using spiking neurons, and Spike-Timing-Dependent Plasticity (STDP)-based learning rule. We propose a biologically plausible sound classification framework that uses a Spiking Neural Network (SNN) for detecting the embedded frequencies contained within an acoustic signal. This work also demonstrates an efficient hardware implementation of the SNN network based on the low-power Spike Continuous Time Neuron (SCTN). The proposed sound classification framework suggests direct Pulse Density Modulation (PDM) interfacing of the acoustic sensor with the SCTN-based network avoiding the usage of costly digital-to-analog conversions. This paper presents a new connectivity approach applied to Spiking Neuron (SN)-based neural networks. We suggest considering the SCTN neuron as a basic building block in the design of programmable analog electronics circuits. Usually, a neuron is used as a repeated modular element in any neural network structure, and the connectivity between the neurons located at different layers is well defined. Thus, generating a modular Neural Network structure composed of several layers with full or partial connectivity. The proposed approach suggests controlling the behavior of the spiking neurons, and applying smart connectivity to enable the design of simple analog circuits based on SNN. Unlike existing NN-based solutions for which the preprocessing phase is carried out using analog circuits and analog-to-digital conversion, we suggest integrating the preprocessing phase into the network. This approach allows referring to the basic SCTN as an analog module enabling the design of simple analog circuits based on SNN with unique inter-connections between the neurons. The efficiency of the proposed approach is demonstrated by implementing SCTN-based resonators for sound feature extraction and classification. The proposed SCTN-based sound classification approach demonstrates a classification accuracy of 98.73% using the Real-World Computing Partnership (RWCP) database.


[Social distribution of AIDS in Brazil, according to labor market participation, occupation and socioeconomic status of cases from 1987 to 1998].
The dynamics of the Brazilian AIDS epidemic was analyzed by occupation, taken as a proxy for individual socioeconomic status. The analysis comprised AIDS cases aged 20-49 and diagnosed in 1987-1998. The temporal trend in AIDS incidence rates was analyzed by sex, occupational category, and quintiles defined by a Brazilian scale for socioeconomic status (SES). The proportions of AIDS cases stratified by SES quintiles were analyzed by exposure category. Among men, incidence rates increased in the 1st time period in almost all occupational categories, decreasing among those classified as "non-manual" occupations during the 2nd period. Among females, an annual increment was observed from 1987 to 1998 in nearly all occupational strata. The highest relative increases were observed among the lowest SES scales for both sexes. The intravenous drug user (IDU) exposure category had the lowest socioeconomic status for both sexes, whereas the homo/bisexual category had the highest. The analysis highlighted a progressive change in the epidemic's social gradient during the period, with a faster spread among the lower socioeconomic strata.


Why did the buffalo cross the park? Resource shortages, but not infections, drive dispersal in female African buffalo (Syncerus caffer).
Dispersal facilitates population health and maintains resilience in species via gene flow. Adult dispersal occurs in some species, is often facultative, and is poorly understood, but has important management implications, particularly with respect to disease spread. Although the role of adult dispersal in spreading disease has been documented, the potential influence of disease on dispersal has received little attention. African buffalo (Syncerus caffer) are wide-ranging and harbor many pathogens that can affect nearby livestock. Dispersal of adult buffalo has been described, but ecological and social drivers of buffalo dispersal are poorly understood. We investigated drivers of adult buffalo dispersal during a 4-year longitudinal study at Kruger National Park, South Africa. We monitored the spatial movement of 304 female buffalo in two focal areas using satellite and radio collars, capturing each buffalo every 6 months to assess animal traits and disease status. We used generalized linear mixed models to determine whether likelihood of dispersal for individual female buffalo was influenced by animal traits, herd identity, environmental variables, gastrointestinal parasites, or microparasite infections. The likelihood and drivers of buffalo dispersal varied by herd, area, and year. In the Lower Sabie herd, where resources were abundant, younger individuals were more likely to disperse, with most dispersal occurring in the early wet season and during an unusually dry year, 2009. In the resource-poor Crocodile Bridge area, buffalo in poor condition were most likely to disperse. Our findings suggest that dispersal of female buffalo is driven by either seasonal (Lower Sabie) or perhaps social (Crocodile Bridge) resource restriction, indicating resource limitation and dispersal decisions are tightly linked for this social ungulate. We found no direct effects of infections on buffalo dispersal, assuaging fears that highly infectious individuals might be more prone to dispersing, which could accelerate the spatial spread of infectious diseases.


Bioethics for clinicians: 23. Disclosure of medical error.
Adverse events and medical errors are not uncommon. In this article we review the literature on such events and discuss the ethical, legal and practical aspects of whether and how they should be disclosed to patients. Ethics, professional policy and the law, as well as the relevant empirical literature, suggest that timely and candid disclosure should be standard practice. Candour about error may lessen, rather than increase, the medicolegal liability of the health care professionals and may help to alleviate the patient's concerns. Guidelines for disclosure to patients, and their families if necessary, are proposed.


Impact of SMS and peer navigation on retention in HIV care among adults in South Africa: results of a three-arm cluster randomized controlled trial.
Few interventions have demonstrated improved retention in care for people living with HIV (PLHIV) in sub-Saharan Africa. We tested the efficacy of two personal support interventions - one using text messaging (SMS-only) and the second pairing SMS with peer navigation (SMS+PN) - to improve HIV care retention over one year. In a cluster randomized control trial (NCT# 02417233) in North West Province, South Africa, we randomized 17 government clinics to three conditions: SMS-only (6), SMS+PN (7) or standard of care (SOC; 4). Participants at SMS-only clinics received appointment reminders, biweekly healthy living messages and twice monthly SMS check-ins. Participants at SMS+PN clinics received SMS appointment reminders and healthy living messages and spoke at least twice monthly with peer navigators (PLHIV receiving care) to address barriers to care. Outcomes were collected through biweekly clinical record extraction and surveys at baseline, six and 12 months. Retention in HIV care over one year was defined as clinic visits every three months for participants on antiretroviral therapy (ART) and CD4 screening every six months for pre-ART participants. We used generalized estimating equations, adjusting for clustering by clinic, to test for differences across conditions. Between October 2014 and April 2015, we enrolled 752 adult clients recently diagnosed with HIV (SOC: 167; SMS-only: 289; SMS+PN: 296). Individuals in the SMS+PN arm had approximately two more clinic visits over a year than those in other arms (p < 0.01) and were more likely to be retained in care over one year than those in SOC clinics (54% vs. 38%; OR: 1.77, CI: 1.02, 3.10). Differences between SMS+PN and SOC conditions remained significant when restricting analyses to the 628 participants on ART (61% vs. 45% retained; OR: 1.78, CI: 1.08, 2.93). The SMS-only intervention did not improve retention relative to SOC (40% vs. 38%, OR: 1.12, CI: 0.63, 1.98). A combination of SMS appointment reminders with personalized, peer-delivered support proved effective at enhancing retention in HIV care over one year. While some clients may only require appointment reminders, the SMS+PN approach offers increased flexibility and tailored, one-on-one support for patients struggling with more substantive challenges.


Serum IgE and Allergy Related Genotypes of IL-4R α and IL-13 Genes: Association with Glioma Susceptibility and Glioblastoma Prognosis.
Gliomas are the commonest type of primary brain tumor in adult. Glioblastoma maltiforms (GBM) is the malignant form with poor prognosis. Certain genotypes of inflammatory gene which associated with asthma and allergic conditions (IL-4R α and IL- 13) are inversely associated with glioma risk. We studied the relation between allergic conditions and serum level of IgE and glioma risk. We also examined the role of SNP of inflammatory genes IL-4 R α (rs 1801275) and IL-13 (rs 1800925) in development of glioma and to find out factors which can modify the prognosis of glioblastoma. This study included 98 Egyptian glioma cases and 98 healthy controls. Full history and clinical data were taken; total serum IgE were assayed, genotyping of IL-4 R α (rs 1801275) and IL-13 (rs 1800925) genes was carried out by restriction digestion after genes amplification. In cases group histopathological examination and tumor grading were done. Past history of allergic condition and elevated serum levels of IgE were more frequent in controls than in cases group (P< 0.05). Genotypes AA and AG of IL- 4R α were significantly frequent in cases and A allele were considered risk factor for glioma OR 2.31(1.53- 3.48), P < 0.001. We also found that C allele of IL-13 is risk factor for glioma susceptibility with p value = 0.006. Longer median survival period in glioblastoma were associated with elevated serum IgE level and who were AA genotypes of IL-4 R α. We conclude an inverse relation between glioma risk, and allergy biomarker IgE and allergy related (IL-4R α; rs 1801275) gene polymorphisms. GBM patients with IL-4Rα AA genotype, have longest survival. Chemotherapy and gross total resection improve GBM prognosis.


Bayesian analysis of longitudinal Johne's disease diagnostic data without a gold standard test.
A Bayesian methodology was developed based on a latent change-point model to evaluate the performance of milk ELISA and fecal culture tests for longitudinal Johne's disease diagnostic data. The situation of no perfect reference test was considered; that is, no "gold standard." A change-point process with a Weibull survival hazard function was used to model the progression of the hidden disease status. The model adjusted for the fixed effects of covariate variables and random effects of subject on the diagnostic testing procedure. Markov chain Monte Carlo methods were used to compute the posterior estimates of the model parameters that provide the basis for inference concerning the accuracy of the diagnostic procedure. Based on the Bayesian approach, the posterior probability distribution of the change-point onset time can be obtained and used as a criterion for infection diagnosis. An application is presented to an analysis of ELISA and fecal culture test outcomes in the diagnostic testing of paratuberculosis (Johne's disease) for a Danish longitudinal study from January 2000 to March 2003. The posterior probability criterion based on the Bayesian model with 4 repeated observations has an area under the receiver operating characteristic curve (AUC) of 0.984, and is superior to the raw ELISA (AUC=0.911) and fecal culture (sensitivity=0.358, specificity=0.980) tests for Johne's disease diagnosis.


Programmable selectivity for GC with series-coupled columns using pulsed heating of the second column.
A series-coupled ensemble of a nonpolar dimethyl polysiloxane column and a polar trifluoropropylmethyl polysiloxane column with independent at-column heating is used to obtain pulsed heating of the second column. For mixture component bands that are separated by the first column but coelute from the column ensemble, a temperature pulse is initiated after the first of the two components has crossed the column junction point and is in the second column, while the other component is still in the first column. This accelerates the band for the first component. If the second column cools sufficiently prior to the second component band crossing the junction, the second band experiences less acceleration, and increased separation is observed for the corresponding peaks in the ensemble chromatogram. High-speed at-column heating is obtained by wrapping the fused-silica capillary column with resistance heater wire and sensor wire. Rapid heating for a temperature pulse is obtained with a short-duration linear heating ramp of 1000 degrees C/min. During a pulse, the second-column temperature increases by 20-100 degrees C in a few seconds. Using a cold gas environment, cooling to a quiescent temperature of 30 degrees C can be obtained in approximately 25 s. The effects of temperature pulse initiation time and amplitude on ensemble peak separation and resolution are described. A series of appropriately timed temperature pulses is used to separate three coeluting pairs of components in a 13-component mixture.


[Polymorphisms of vascular diseases-related genes in Guangzhou Biobank Cohort Study].
To study the polymorphisms of cerebrovascular and cardiovascular disease genes using Taqman single nucleotide polymorphism (SNP) genotyping kits. A total of 2000 subjects were recruited from the Guangzhou Biobank Cohort Study (GBCS), and 15 SNPs were detected using Taqman SNP genotyping kits and an ABI 7900HT real time PCR system. The data were tested for the Hardy-Weinberg equilibrium, and then compared with the data of the Chinese population from the International HapMap Project (HapMap_HCN). (1) All genotype data of the 15 SNPs were consistent with the Hardy-Weinberg rules. (2) The significant differences were observed among two SNPs, rs4220 and rs5368 and the HapMap_HCN (rs4220 28.2% vs 17.8%; chi(2) = 4.891, P = 0.028; rs5368 22.1% vs 32.2%, chi(2) = 5.137, P = 0.024). Comparing other gene bank data, such as AFD-CHN-PANEL, the Allele Frequency Database (ALFRED) and JBIC-allele, it would be most likely that our observations represent differences between the Northern and Southern populations in China. Such Biobank study provided a useful platform for the study of the role of genetic and environmental determinants on cerebrovascular and cardiovascular disease.


The role of user representation and Arthritis and Rheumatism International.
Arthritis and Rheumatism International (ARi), founded in 1988, is an association of national lay organizations comprising mainly people whose lives are affected by arthritis and rheumatism. ARi's charter defines the organization's aims, including to raise awareness of the needs of people with arthritis/rheumatism, to improve the quality of their lives through education and self-management programs, and to support research into causes, management, prevention, and cure of arthritis. With the aid of a grant from the Pfizer Foundation in 2002, ARi has been able to further develop into a strong organization throughout the world, with a membership of 22 countries. Successful intitiatives include the People with Arthritis and Rheumatism in Europe Manifesto, which has served as a very effective focus for developing action plans, opening dialogues, building partnerships with other organizations, lobbying governments, and gaining media attention throughout Europe. The manifesto (website: www.PAREmanifesto.org) was developed by ARi working in conjunction with The International Organisation of Youth with Rheumatism and the EULAR Social League. These are examples of initiatives that ARi aims to promote on a global scale in the next few years.


Massive blood loss during tonsillectomy in a child with congenital venous malformation.
Tonsillectomy and adenoidectomy have become frequently performed outpatient procedures and are generally considered to have a low morbidity profile. Postoperative haemorrhage remains a rare but important complication, while intraoperative uncontrollable bleeding is extremely uncommon. A child with congenital vascular malformation of the lip and oropharynx undergoing tonsillectomy experienced massive blood loss, subsequent resuscitation and significant perioperative morbidity including a prolonged intensive care unit stay. Preoperative/preanaesthetic nasopharyngoscopic exam and magnetic resonance imaging did not reveal vascular prominence of the tonsils. Preoperative consideration of angiography or magnetic resonance angiography may be prudent to avoid this potentially fatal complication.


[Changes of nucleolin expression and cellular localization during HUVEC apoptosis induced by hydrogen peroxide].
To investigate the expression and cellular localization of nucleolin C23 during human umbilical vein endothelial cell (HUVEC) apoptosis induced by hydrogen peroxide (H(2)O(2)). Apoptosis of HUVEC was induced by exposure to 0.5 mmol/L H(2)O(2) for different periods and detected by flow cytometry and activity of caspase-3. The mRNA and protein expression of nucleolin were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The intracellular distribution of nucleolin was observed by indirect immunofluorescence. The percentage of apoptotic cells was increased significantly after treatment with H(2)O(2) for 12, 24 and 36 hours. The activity of caspase-3 reached the peak after treatment with H(2)O(2) for 4 h. RT-PCR showed that nucleolin C23 mRNA was decreased after 2, 4, and 8 hours treatment with H(2)O(2). Western blot showed that C23 protein level was decreased after 12 hours with an additional cleft band of 80 kD appeared after 8 hours. Density analysis showed that the 80 kD cleft band increased in a time-dependent manner. Immunofluorescence analysis demonstrated that H(2)O(2)-induced C23 redistribution from the nucleus to the cytoplasm. H(2)O(2) could induce apoptosis accompanying with C23-cleavage and C23-translocation from the nucleus to the cytoplasm.


Malaria in the Greater Mekong Subregion: heterogeneity and complexity.
The Greater Mekong Subregion (GMS), comprised of six countries including Cambodia, China's Yunnan Province, Lao PDR, Myanmar (Burma), Thailand and Vietnam, is one of the most threatening foci of malaria. Since the initiation of the WHO's Mekong Malaria Program a decade ago, malaria situation in the GMS has greatly improved, reflected in the continuous decline in annual malaria incidence and deaths. However, as many nations are moving towards malaria elimination, the GMS nations still face great challenges. Malaria epidemiology in this region exhibits enormous geographical heterogeneity with Myanmar and Cambodia remaining high-burden countries. Within each country, malaria distribution is also patchy, exemplified by 'border malaria' and 'forest malaria' with high transmission occurring along international borders and in forests or forest fringes, respectively. 'Border malaria' is extremely difficult to monitor, and frequent malaria introductions by migratory human populations constitute a major threat to neighboring, malaria-eliminating countries. Therefore, coordination between neighboring countries is essential for malaria elimination from the entire region. In addition to these operational difficulties, malaria control in the GMS also encounters several technological challenges. Contemporary malaria control measures rely heavily on effective chemotherapy and insecticide control of vector mosquitoes. However, the spread of multidrug resistance and potential emergence of artemisinin resistance in Plasmodium falciparum make resistance management a high priority in the GMS. This situation is further worsened by the circulation of counterfeit and substandard artemisinin-related drugs. In most endemic areas of the GMS, P. falciparum and Plasmodium vivax coexist, and in recent malaria control history, P. vivax has demonstrated remarkable resilience to control measures. Deployment of the only registered drug (primaquine) for the radical cure of vivax malaria is severely undermined due to high prevalence of glucose-6-phosphate dehydrogenase deficiency in target human populations. In the GMS, the dramatically different ecologies, diverse vector systems, and insecticide resistance render traditional mosquito control less efficient. Here we attempt to review the changing malaria epidemiology in the GMS, analyze the vector systems and patterns of malaria transmission, and identify the major challenges the malaria control community faces on its way to malaria elimination.


Carcinoma ex pleomorphic adenoma of the salivary gland: an immunohistochemical study.
The proliferative activity of the tumor cells and the expression of tumor-associated genes and sex steroid hormone receptors were investigated immunohistochemically in ten cases of carcinoma ex pleomorphic adenoma (Ca-ex-PA) of the salivary glands. These were analyzed in benign and malignant components separately, and then were compared with ten cases of the other malignant tumors [adenocarcinomas, not otherwise specified (ACN) and salivary duct carcinomas (SDC)] and ten cases of pleomorphic adenomas (PA). The results obtained in this study were as follows: (1) malignant component of Ca-ex-PA showed a higher incidence of PCNA and Ki67 than benign component of Ca-ex-PA. A significant difference between benign component of Ca-ex-PA and PA was not observed. (2) A significant difference in the incidence of p53, c-erbB-2, EGFR overexpression was observed only between malignant component of Ca-ex-PA and benign component of Ca-ex-PA. (3) The incidence of PCNA, Ki67, p53, c-erbB-2 overexpression in malignant component of Ca-ex-PA showed the highest data among the four groups. These results suggest that Ca-ex-PA acquired the particular biological behavior in contrast to the other salivary neoplasms in the long-standing process while PA undergoes malignant transformation.


Inhibition by chlorogenic acid of haematin-catalysed retinoic acid 5,6-epoxidation.
Chlorogenic acid (3-O-caffeoylquinic acid) inhibited haematin- and haemoglobin-catalysed retinoic acid 5,6-epoxidation. Some other phenol compounds (caffeic acid and 4-hydroxy-3-methoxybenzoic acid) also showed inhibitory effects on the haematin- and haemoglobin-catalysed epoxidation, but salicylic acid did not. Of the above compounds, caffeic acid and chlorogenic acid were potent inhibitors compared with the other two, suggesting that the o-hydroquinone moiety of chlorogenic acid and caffeic acid is essential to the inhibition of the epoxidation. Although caffeic acid inhibited retinoic acid 5,6-epoxidation requiring the consumption of O2, formation of retinoic acid radicals was not inhibited on the addition of caffeic acid to the incubation mixture. The above results suggest that caffeic acid does not inhibit the formation of retinoic acid radicals but does inhibit the step of conversion of retinoic acid radical into the 5,6-epoxide.


Differential Effect of Left vs. Right White Matter Hyperintensity Burden on Functional Decline: The Northern Manhattan Study.
Asymmetry of brain dysfunction may disrupt brain network efficiency. We hypothesized that greater left-right white matter hyperintensity volume (WMHV) asymmetry was associated with functional trajectories. Methods: In the Northern Manhattan Study, participants underwent brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions was determined separately by combining bimodal image intensity distribution and atlas based methods. Participants had annual functional assessments with the Barthel index (BI, range 0-100) over a mean of 7.3 years. Generalized estimating equations (GEE) models estimated associations of regional WMHV and regional left-right asymmetry with baseline BI and change over time, adjusted for baseline medical risk factors, sociodemographics, and cognition, and stroke and myocardial infarction during follow-up. Results: Among 1,195 participants, greater WMHV asymmetry in the parietal lobes (-8.46 BI points per unit greater WMHV on the right compared to left, 95% CI -3.07, -13.86) and temporal lobes (-2.48 BI points, 95% CI -1.04, -3.93) was associated with lower overall function. Greater WMHV asymmetry in the parietal lobes (-1.09 additional BI points per year per unit greater WMHV on the left compared to right, 95% CI -1.89, -0.28) was independently associated with accelerated functional decline. Conclusions: In this large population-based study with long-term repeated measures of function, greater regional WMHV asymmetry was associated with lower function and functional decline. In addition to global WMHV, WHMV asymmetry may be an important predictor of long-term functional status.


p21+/+ (CDKN1A+/+) and p21-/- (CDKN1A-/-) human colorectal carcinoma cells display equivalent amounts of thermal radiosensitization.
The mechanism of thermal radiosensitization is related to the inhibition of repair of radiation-induced DNA damage by heat. Due to the interaction of the gene p21/WAF1/CIP1 (now known as CDKN1A) with a variety of DNA repair proteins, its involvement in thermal radiosensitization was investigated. Two isogenetic human colorectal cancer cell lines with wild-type TP53 status were used. The 80S4 cell line was deficient in CDKN1A and the HCT116 cells were CDKN1A proficient. Both cell lines were significantly more sensitive to 44 degrees C than 42 degrees C heating (P < 0.01), and both cell lines expressed thermotolerance for heating times longer than about 2 h at the lower temperature. There were no significant differences in the X-radiation response of the two cell lines. Further, the two cell lines displayed similar cell survival levels after hyperthermia given before or after X radiation for both hyperthermia temperatures. Comparison of thermal enhancement ratios confirmed that there was no difference in the amount of thermal radiosensitization induced in the two cell lines. The induction and subsequent repair of DNA double-strand breaks, as measured by clamped homogeneous gel electrophoresis, was also the same in both cell lines. These findings strongly suggest that the gene CDKN1A does not play an important role in the expression of thermal radiosensitization.


Galectin-3 inhibits tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by activating Akt in human bladder carcinoma cells.
The antiapoptotic molecule galectin-3 was previously shown to regulate CD95, a member of the tumor necrosis factor (TNF) family of proteins in the apoptotic signaling pathway. Here, we question the generality of the phenomenon by studying a different member of this family of proteins [e.g., TNF-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in a wide variety of cancer cells]. Overexpression of galectin-3 in J82 human bladder carcinoma cells rendered them resistant to TRAIL-induced apoptosis, whereas phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY-294002) blocked the galectin-3 protecting effect. Because Akt is a major downstream PI3K target reported to play a role in TRAIL-induced apoptosis, we questioned the possible relationship between galectin-3 and Akt. Parental J82 and the control vector-transfected J82 cells (barely detectable galectin-3) exhibit low level of constitutively active Akt, resulting in sensitivity to TRAIL. On the other hand, J82 cells overexpressing galectin-3 cells expressed a high level of constitutively active Akt and were resistant to TRAIL. Moreover, the blockage of TRAIL-induced apoptosis in J82 cells seemed to be mediated by Akt through the inhibition of BID cleavage. These results suggest that galectin-3 involves Akt as a modulator molecule in protecting bladder carcinoma cells from TRAIL-induced apoptosis.


Molecular epidemiology of SARS-CoV-2 clusters caused by asymptomatic cases in Anhui Province, China.
COVID-19 is a newly emerging disease caused by a novel coronavirus (SARS-CoV-2), which spread globally in early 2020. Asymptomatic carriers of the virus contribute to the propagation of this disease, and the existence of asymptomatic infection has caused widespread fear and concern in the control of this pandemic. In this study, we investigated the origin and transmission route of SARS-CoV-2 in Anhui's two clusters, analyzed the role and infectiousness of asymptomatic patients in disease transmission, and characterized the complete spike gene sequences in the Anhui strains. We conducted an epidemiological investigation of two clusters caused by asymptomatic infections sequenced the spike gene of viruses isolated from 12 patients. All cases of the two clusters we investigated had clear contact histories, both from Wuhan, Hubei province. The viruses isolated from two outbreaks in Anhui were found to show a genetically close link to the virus from Wuhan. In addition, new single nucleotide variations were discovered in the spike gene. Both clusters may have resulted from close contact and droplet-spreading and asymptomatic infections were identified as the initial cause. We also analyzed the infectiousness of asymptomatic cases and the challenges to the current epidemic to provided information for the development of control strategies.


[A natural focus of sandfly fever in the Republic of Afghanistan].
The serological study of persons contacting dengue-like fever in 1987 in Afghanistan (in Rukha, Parwān Province) revealed that in 74% of cases an increase in the titers of antibodies to Sicilian and Neapolitan sandfly [correction of mosquito-borne] fever viruses was registered. Considering that such diseases appeared here for a number of years and were linked in time with the activity of sandflies [correction of mosquitoes] of the species Phlebotomus papatasii, the suggestion was made on the existence of a stable natural focus of sandfly [correction of mosquito-borne] fevers in the region of Rukha.


VCAM-1: closing the gap between lipotoxicity and endothelial dysfunction in nonalcoholic steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) results in the accumulation of fat in the liver and can progress as an inflammatory disorder with considerable vascular endothelial dysfunction known as nonalcoholic steatohepatitis (NASH). Inflammatory signals can trigger the expression of vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells. VCAM-1 is a surface protein that induces adherence and extravasation of monocytes to blood vessels. In this issue of the JCI, Furuta et al. report on their sequencing of RNA transcripts from the livers of mice fed a NASH-inducing diet. VCAM-1 was upregulated in the whole liver as well as liver sinusoidal endothelial cells (LSECs). When the researchers incubated LSECs with palmitate, a toxic lipid, VCAM-1 was upregulated. Notably, inhibiting VCAM-1 in the NASH model reduced VCAM-1 expression, lessened infiltrating macrophages, and mitigated fibrosis. This study connects steatosis to endothelial dysfunction and inflammation and suggests that targeting VCAM-1 may address fibrosis in patients with NASH.


Growth of Colloidal Nanoplate Liquid Crystals Using Temperature Gradients.
Controlling colloidal self-assemblies using external forces is essential to develop modern electro-optical and biomedical devices. Importantly, shape anisotropic colloids can provide optical properties such as birefringence. Here we demonstrate that external temperature gradients can be effective in controlling nematic liquid crystalline (LC) order in suspensions of plate-like colloids also known as nanoplates. Nanoplates, in an isotropic suspension, wherein their orientations are random, could be effectively moved using a temperature gradient environment causing a phase transition to LC nematic phase. Such controllably formed nematic phase featured large nematic monodomains and enabled topologically more stable structures that were evident from the absence of hedgehog-type defects which are typically found in nematics formed spontaneously via nucleation and growth mechanism in a sufficiently high concentration suspension of nanoplates. Due to their high surface area-to-volume ratio and excellent thermophoretic properties, nanoplates can prove to be ideal candidates for transport of biomolecules through temperature varying environments.


Modulation of inositol phospholipid metabolism by polyamines.
At low concentrations of Mg2+, incorporation of 32P from [gamma-32P]ATP into phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) in plasma membranes isolated from human polymorphonuclear leucocytes was enhanced 2-4-fold by the polyamines spermidine and spermine. Polyamines had no effects on inositol phospholipid phosphorylation at high concentrations of Mg2+. At 1 mM-Mg2+, [32P]PIP2 synthesis was maximally enhanced by 2 mM-spermine and 5 mM-spermidine, whereas putrescine only slightly enhanced synthesis. Spermine decreased the EC50 (concn. for half-maximal activity) for Mg2+ in [32P]PIP2 synthesis from 5 mM to 0.5 mM. Spermine did not modulate the Km for ATP for [32P]PIP or [32P]PIP2 synthesis. Spermine also decreased the EC50 for PI in [32P]PIP synthesis. In contrast, spermine elevated the apparent Vmax, without affecting the EC50 for PIP, for [32P]PIP2 synthesis. Spermine and spermidine also inhibited the hydrolysis of [32P]PIP2 by phosphomonoesterase activity. Therefore polyamines appear to activate inositol phospholipid kinases by eliminating the requirements for super-physiological concentrations of Mg2+. Polyamine-mediated inhibition of polyphosphoinositide hydrolysis would serve to potentiate further their abilities to promote the accumulation of polyphosphoinositides in biological systems.


Effects of Filler Distribution on Magnetorheological Silicon-Based Composites.
The smart materials subclass of magnetorheological elastomer (MRE) composites is presented in this work, which aimed to investigate the influence of filler distribution on surface morphology. Iron particles with sizes ranging from 20 to 150 µm were incorporated into the elastomer matrix and a 30% volume fraction (V%) was chosen as the optimal quantity for the filler amount in the elastomer composite. The surface morphology of MRE composites was examined by 3D micro-computed tomography (µCT) and scanning electron microscopy (SEM) techniques. Isotropic and anisotropic distributions of the iron particles were estimated in the magnetorheological elastomer composites. The filler particle distribution at various heights of the MRE composites was examined. The isotropic distribution of filler particles was observed without any influence from the magnetic field during sample preparation. The anisotropic arrangement of iron fillers within the MRE composites was observed in the presence of a magnetic field during fabrication. It was shown that the linear arrangement of the iron particle chain induced magnetization within the composite. Simulation analysis was also performed to predict the particle distribution of magnetization in the MREs and make a comparison with the experimental observations.


[Mutual influence of gastrointestinal pathology and hospital-acquired infection].
Review of the literature devoted to one of the most important problems of modern medicine--nosocomial infections (NI). In the article there are examined relevant, epidemiology, pathogenesis, and criteria for NO determining. Special attention is paid to the mutual influence of gastrointestinal tract pathology and nosocomial infections.