The effect of guanidinium chloride on the behaviour of human cervical-mucus glycoproteins. Evidence for unfolding regions of ordered structure in 6M-guanidinium chloride.
The macromolecular properties of cervical-mucus glycoproteins (mucins) were studied as a function of the concentration of guanidinium chloride with conventional light-scattering, photon-correlation spectroscopy and sedimentation-velocity centrifugation. No evidence for an association of the mucins in 0.2M-NaCl as compared with 6M-guanidinium chloride was found at mucin concentrations below approx. 0.5 mg/ml. However, an increase in the frictional coefficient and in the radius of gyration occurred with increasing concentrations of guanidinium chloride, in particular between 4 M and 6 M, suggesting an expansion of the individual macromolecule. The change in the particle-scattering function is consistent with a transition from a 'stiff' random coil in 0.2 M-NaCl into a more flexible one in 6 M-guanidinium chloride. We suggest that the mucins contain regions of 'ordered' structure which can undergo a reversible 'unfolding' analogous to the behaviour of a conventional globular protein exposed to a denaturing solvent. Such regions might carry sites for specific interactions between mucins and/or be decisive for their conformation and macromolecular properties in physiological solvents.


Dose-dependent effects of L-carnosine on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats.
The physiological function of L-carnosine (beta-alanyl-L-histidine) synthesized in mammalian muscles has been unclear. Previously, we observed that intravenous (i.v.) injection of L-carnosine suppressed renal sympathetic nerve activity (RSNA) in urethane-anesthetized rats, and L-carnosine administered via the diet inhibited the elevation of blood pressure (BP) in deoxycorticosterone acetate salt hypertensive rats. To identify the mechanism, we examined effects of i.v. or intralateral cerebral ventricular (l.c.v.) injection of various doses of L-carnosine on RSNA and BP in urethane-anesthetized rats. Lower doses (1 microg i.v.; 0.01 microg l.c.v.) of L-carnosine significantly suppressed RSNA and BP, whereas higher doses (100 microg i.v.; 10 microg l.c.v.) elevated RSNA and BP. Furthermore, we examined effects of antagonists of histaminergic (H1 and H3) receptors on L-carnosine-induced effects. When peripherally and centrally given, thioperamide, an H3 receptor antagonist, blocked RSNA and BP decreases induced by the lower doses of peripheral L-carnosine, whereas diphenhydramine, an H1 receptor antagonist, inhibited increases induced by the higher doses of peripheral L-carnosine. Moreover, bilateral lesions of the hypothalamic suprachiasmatic nucleus eliminated both effects on RSNA and BP induced by the lower (1 microg) and higher (100 microg) doses of peripheral L-carnosine. These findings suggest that low-dose L-carnosine suppresses and high-dose L-carnosine stimulates RSNA and BP, that the suprachiasmatic nucleus and histaminergic nerve are involved in the activities, and that L-carnosine acts in the brain and possibly other organs.


The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis.
Uridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators. URT1 directly interacts with DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6, and this interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. Based on in vitro and in planta data, we propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3' terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development.


Spot measurement of heart rate based on morphology of PhotoPlethysmoGraphic (PPG) signals.
Due to increasing health consciousness among people, it is imperative to have low-cost health care devices to measure the vital parameters like heart rate and arterial oxygen saturation (SpO2). In this paper, an efficient heart rate monitoring algorithm based on the morphology of photoplethysmography (PPG) signals to measure the spot heart rate (HR) and its real-time implementation is proposed. The algorithm does pre-processing and detects the onsets and systolic peaks of the PPG signal to estimate the heart rate of the subject. Since the algorithm is based on the morphology of the signal, it works well when the subject is not moving, which is a typical test case. So, this algorithm is developed mainly to measure the heart rate at on-demand applications. Real-time experimental results indicate the heart rate accuracy of 99.5%, mean absolute percentage error (MAPE) of 1.65%, mean absolute error (MAE) of 1.18 BPM and reference closeness factor (RCF) of 0.988. The results further show that the average response time of the algorithm to give the spot HR is 6.85 s, so that the users need not wait longer to see their HR. The hardware implementation results show that the algorithm only requires 18 KBytes of total memory and runs at high speed with 0.85 MIPS. So, this algorithm can be targeted to low-cost embedded platforms.


The trapeziometacarpal joint. Tenotomy of the accessory tendons in early osteoarthritis.
The TMC joint is an articulation with special articular surfaces adapted to produce simple (nonrotatory) and complex (rotatory) metacarpal movements. Its articular anatomy and biomechanics are closely related to the pathogenesis of osteoarthritis. The joint works under high transarticular compressive-shearing forces. In osteoarthritic thumbs, the articular forces are increased because of the constant presence of accessory APL tendons, almost exclusively of the digastric type. Other factors should be considered in the pathogenesis of TMC joint osteoarthritis, such as repetitive use of the thumb under unfavorable patterns of function) strong side-to-side pinch grips, thumb with the tendency to maintain in reposition), cartilage aging, hormonal disturbances in women, and general osteoarthritic disease. Osteoarthritic thumbs in stages I and II that have failed to respond to conservative treatment are candidates to unload the joint by tenotomy of the transarticular accessory tendons. Long-term results have been very satisfactory (97%), eliminating or substantially reducing pain and returning patients to their activity. The procedure is contraindicated in severe (stage III) TMC joint osteoarthritis and in primary articular instability.


The Impending Epidemic of Cardiovascular Diseases in Patients With Cancer in Japan.
Onco-cardiology, a new academic field, aims to improve the quality of life and prognosis of cancer patients and survivors with cardiovascular diseases (CVD). With the aging of the population, an epidemic of cancer with CVD is emerging in developed countries. Cancer and CVD share risk factors, pathophysiology, treatments, and preventive and rehabilitative measures. A multidisciplinary team-based approach is needed to support cancer treatment to maximize its effectiveness and minimize its cardiotoxic potential. Basic and clinical onco-cardiology are already being practiced harmoniously. However, systematization in academia and clinical practice and accumulation of evidence have just started. In this review, we present the epidemiology, common risk factors between cancer and CVD, future epidemic of CVD in patients with cancer, and the necessity for an onco-cardiological approach to managing the burden of CVD in cancer patients and survivors.


From famine to therapeutic weight loss: Hunger, psychological responses, and energy balance-related behaviors.
Understanding physiological and behavioral responses to energy imbalances is important for the management of overweight/obesity and undernutrition. Changes in body composition and physiological functions associated with energy imbalances provide the structural and functional context in which to consider psychological and behavioral responses. Compensatory changes in physiology and behavior are more pronounced in response to negative than positive energy balances. The physiological and psychological impact of weight loss (WL) occur on a continuum determined by (i) the degree of energy deficit (ED), (ii) its duration, (iii) body composition at the onset of the energy deficit, and (iv) the psychosocial environment in which it occurs. Therapeutic WL and famine/semistarvation both involve prolonged EDs, which are sometimes similar in magnitude. The key differences are that (i) the body mass index (BMI) of most famine victims is lower at the onset of the ED, (ii) therapeutic WL is intentional and (iii) famines are typically longer in duration (partly due to the voluntary nature of therapeutic WL and disengagement with WL interventions). The changes in psychological outcomes, motivation to eat, and energy intake in therapeutic WL are often modest (bearing in mind the nature of the measures used) and can be difficult to detect but are quantitatively significant over time. As WL progresses, these changes become more marked. It appears that extensive WL beyond 10%-20% in lean individuals has profound effects on body composition and physiological function. At this level of WL, there is a marked erosion of psychological functioning, which appears to run in parallel to WL. Psychological resources dwindle and become increasingly focused on alleviating escalating hunger and food seeking behavior. Functional changes in fat-free mass, characterized by catabolism of skeletal muscle and organs may be involved in the drive to eat associated with semistarvation. Higher levels of body fat mass may act as a buffer to protect fat-free mass, functional integrity and limit compensatory changes in energy balance behaviors. The increase in appetite that accompanies therapeutic WL appears to be very different to the intense and all-consuming drive to eat that occurs during prolonged semistarvation. The mechanisms may also differ but are not well understood, and longitudinal comparisons of the relationship between body structure, function, and behavior in response to differing EDs in those with higher and lower BMIs are currently lacking.


miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology.
Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.


[Comparing loss of anterior column height and cervical Cobb angle with three different types of anterior cervical discectomy and fusion].
To compare the loss of anterior column height and cervical Cobb angle with three different types of anterior cervical discectomy and fusion (ACDF). A prospective randomized study was performed on 60 patients who had undergone ACDF with the autologous iliac crest graft (group A, n=20), the autogenous bone and the anterior cervical locking plates (group B, n=20), and Syncage-C filled with the local autograft reamings (group C, n=20) from January 1998 to January 2003. The patients diagnosed as having cervical radiculopathy (RP) and cervical spondylotic myelopathy (CSM) were indicated for ACDF. Of the patients, 41 were male and 19 female with a mean age of 57 years (range, 36-68) and their average course of disease was 6.2 months (range, 1-36). There were 36 one-level and 24 two-level fusions from C(3,4) to C7, T1. Radiological measurements were performed on the cervical radiographs taken before operation, 7 days and 3 months after operation, and on the last day of the follow-up; then, the height and Cobb angle of the fused segment, functional restoration, and clinical outcome were evaluated in the three groups. The follow-up of more than 2 years (range, 2-7) showed that the average loss of anterior column height and Cobb angle of the fused segments in groups A and B, which had not preserved the endplate, had a greater increase than that in group C, which had preserved the endplate. Of the patients, 12 had autograft collapse, 3 autograft displacement, and 10 postural abnormality between the fused segments, most of which happened in groups A and B. The fusion rate was 93.3% (56 cases) according the strict arthrodesis criteria; their excellent and good rate in the functional assessment was 83.3% (RP 90.4%, CSM 79.5%); the overall satisfactory (excellent and good) rates in groups A, B and C were 75%, 85% and 90%, respectively. To increase the resistance to graft subsidence, which is a major reason for narrowness of the fused segments, and to maintain normal cervical curvature, we should improve our skills of bone grafting performance, preserve the endplate, carefully evaluate the degree of osteoporosis before operation, and use anterior cervical locking plate and/or fusion with Syncage-C when necessary.


Moesin is involved in microglial activation accompanying morphological changes and reorganization of the actin cytoskeleton.
Moesin is a member of the ezrin, radixin and moesin (ERM) proteins that are involved in the formation and/or maintenance of cortical actin organization through their cross-linking activity between actin filaments and proteins located on the plasma membranes as well as through regulation of small GTPase activities. Microglia, immune cells in the central nervous system, show dynamic reorganization of the actin cytoskeleton in their process elongation and retraction as well as phagocytosis and migration. In microglia, moesin is the predominant ERM protein. Here, we show that microglial activation after systemic lipopolysaccharide application is partly inhibited in moesin knockout (Msn-KO) mice. We prepared primary microglia from wild-type and Msn-KO mice, and studied them to compare their phenotypes accompanying morphological changes and reorganization of the actin cytoskeleton induced by UDP-stimulated phagocytosis and ADP-stimulated migration. The Msn-KO microglia showed higher phagocytotic activity in the absence of UDP, which was not further increased by the treatment with UDP. They also exhibited decreased ADP-stimulated migration activities compared with the wild-type microglia. However, the Msn-KO microglia retained their ability to secrete tumor necrosis factor α and nitric oxide in response to lipopolysaccharide.


Preventing invasive fungal disease in patients with haematological malignancies and the recipients of haematopoietic stem cell transplantation: practical aspects.
Invasive fungal disease (IFD), predominantly aspergillosis, is associated with significant morbidity and mortality in immunocompromised patients, especially those with haematological malignancies and recipients of allogeneic haematopoietic stem cell transplantation. There has been a great deal of scientific debate as to the effectiveness of antifungal prophylaxis in preventing infection in different patient groups and in which patients it is an appropriate management option. Deciding on an appropriate prophylaxis regimen for IFD is challenging as the incidence varies among different patient groups, due to the varied nature of their underlying haematological disease, and in different regions and centres. Attempts have been made to define risk factors and include them in treatment protocols. Impaired immune status of the patient, especially neutropenia, is a key risk factor for IFD and can sometimes be related to specific polymorphisms of genes controlling innate immunity. Risk factors also vary according to the type of fungal pathogen. Consequently, prophylaxis needs to be tailored to individual patient groups. Furthermore, the choice of antifungal agent for prophylaxis depends on the potential for drug-drug interactions with the patients' concomitant medications. Additional challenges are optimal timing of antifungal prophylaxis, when to change from prophylaxis to antifungal treatment and how to prevent recurrence of IFD. This article considers the use of antifungal prophylaxis for patients at risk of IFD in daily clinical practice, with clinical profiles that may be distinct from those covered by guidelines, and aims to provide practical advice for treatment of these patient groups.


Can real-time visual feedback during gait retraining reduce metabolic demand for individuals with transtibial amputation?
The metabolic demand of walking generally increases following lower extremity amputation. This study used real-time visual feedback to modify biomechanical factors linked to an elevated metabolic demand of walking in individuals with transtibial amputation. Eight persons with unilateral, traumatic transtibial amputation and 8 uninjured controls participated. Two separate bouts of real-time visual feedback were provided during a single session of gait retraining to reduce 1) center of mass sway and 2) thigh muscle activation magnitudes and duration. Baseline and post-intervention data were collected. Metabolic rate, heart rate, frontal plane center of mass sway, quadriceps and hamstrings muscle activity, and co-contraction indices were evaluated during steady state walking at a standardized speed. Visual feedback successfully decreased center of mass sway 12% (p = 0.006) and quadriceps activity 12% (p = 0.041); however, thigh muscle co-contraction indices were unchanged. Neither condition significantly affected metabolic rate during walking and heart rate increased with center-of-mass feedback. Metabolic rate, center of mass sway, and integrated quadriceps muscle activity were all not significantly different from controls. Attempts to modify gait to decrease metabolic demand may actually adversely increase the physiological effort of walking in individuals with lower extremity amputation who are young, active and approximate metabolic rates of able-bodied adults.


The ailing gut: a therapeutic role for bone marrow cells?
It is obvious that the BM does more than simply supply the GIT with cells of the innate and adaptive immune system. A growing number of studies suggest that BMCs can differentiate into ISEMFs (Lee et al., PLOS ONE 2011;6:e26082) and in the setting of inflammation can be contributors to all lineages of the neovasculature. The role of BMCs in epithelial turnover is more problematic; their contribution after transient mucosal injury seems negligible, but a number of studies in both rodents and man suggest that small numbers of BMCs can be incorporated into the epithelial compartment with more chronic injury (e.g., GvHD in man and chemically induced colitis in rodents); commonly cell fusion seems to be responsible for this. Significantly, this engraftment does not seem to occur in the stem-cell compartment, with the notable single report of the chronically infected murine gastric mucosa, where the BM origin of the stem cells can be the only rational explanation for the complete colonization of the mucosa by BMDCs. In the clinical setting, a role for MSCs in ameliorating colitis seems promising, though the mechanisms by which this is achieved remain somewhat unclear, though both immunomodulatory and regenerative effects of BMCs are likely to be important.


Giant pilomatricoma (pilomatrixoma) following an intramuscular injection.
We describe a young Indian male patient who developed a large solitary tumor following an intramuscular injection at the same location. The tumor was histologically proven to be a pilomatricoma. It was treated by surgical excision and there was no recurrence until one year after the operation. An alarming phenomenon following intramuscular injection is presented here for its novelty.


Wheezing conditions in early childhood: prevalence and risk factors in the city of São Paulo, Brazil.
To investigate the prevalence and risk factors for wheezing disorders in early childhood in São Paulo, Brazil, the largest metropolitan area of South America. A population-based cross-sectional survey of 1132 children aged 6-59 months was carried out between 1995 and 1996 to obtain information on recent wheezing and on independent variables such as demographic, socioeconomic, environmental, maternal and nutritional variables and immunization status. Intestinal parasitic infections were diagnosed using standard techniques. Multiple unconditional logistic regression was used to describe associations between outcome and independent variables. The prevalence of recent wheezing (one or more reported episodes in the past 12 months) was 12.5%; 93% of children with wheezing were also reported to have a medical diagnosis of asthma. Recent wheezing was associated with low per capita income, poor quality of housing, day-care attendance, low birth weight and infection with intestinal helminths. Wheezing in early childhood in São Paulo, although more common than in most developing countries, remains less prevalent than in urban areas of industrialized countries. Low income and conditions associated with poverty (poor housing, low birth weight and parasitic infections) are some of the main risk factors for wheezing disorders among young children in this city.


From Genetically Altered Mice to Integrative Physiology.
Transgenic and gene-targeted mice permit the study of the function(s) of the single gene(s) in a whole organism, thereby relating molecular biology and integrative physiology. To demonstrate the potential of transgenic models, we present in this review some physiologically relevant information obtained from genetically engineered mice.


Development of a Novel Freeze-dried Mulberry Leaf Extract-based Transfersome Gel.
Nowadays, antioxidants are important for health-related concerns related to acne vulgaris. Acne vulgaris is interrelated with the development of free radicals that interact with cells. Mulberry leaves contain phenolic compounds, including antioxidants such as quercetin. An antioxidant is a scavenger of free radicals. The current study addresses the development of a mulberry leaf extract-based transfersome gel containing quercetin by a thin-layer hydration method for topical antioxidant delivery. The process was optimized by encapsulating the drug in a variety of transfersome formulations. Batch optimization was carried out by particle size and zeta analysis, entrapment efficiency (%), polydispersity index, in vitro drug release, and drug content analysis. The optimized batch MF5 provided 86.23% entrapment efficiency of quercetin in the vesicles and 95.79% drug release. It furnished a spherical shaped vesicle with an average diameter of 118.7 nm and zeta potential of -45.11 mV. The MG1 formulation provided superior antioxidant activity, drug content, and entrapment efficiency, ex vivo drug release, spreadability, homogeneity, and stability to MG2. The presence of quercetin in the extract and gel formulation was confirmed by using high performance thin layer chromatography. It is evident from this study that a mulberry leaf extract-based transfersome gel is a promising prolonged delivery system for quercetin and has reasonably good stability characteristics. This research recommends that mulberry leaf extract-based transfersome gel can potentially be used in the treatment of acne vulgaris through a transdermal drug delivery system.


Bombesin-induced pancreatic secretion and growth in rats: effect of proglumide, spantide and ranitidine.
The effect of proglumide (400 mg/kg), spantide (400 g/kg) and ranitidine (20 mg/kg) on pancreatic secretory and trophic response to bombesin (10 micrograms/kg) was studied in the rat. Drugs were administered alone or combined with bombesin three times daily for 5 days. Saline-treated rats were used as controls. At the end of treatment, animals were anaesthetized and pancreatic juice was collected for 1 h after caerulein stimulation (1 microgram/kg intraperitoneally). Afterwards, rats were sacrificed and the weight and composition of pancreatic tissue were determined. As compared with control (saline) values, the volume of pancreatic juice and the output of trypsin and amylase were increased by treatment with bombesin. Neither proglumide nor spantide affected basal and caerulein-stimulated pancreatic exocrine secretion. Ranitidine, although unable to modify protein and enzyme content of pancreatic secretion, significantly reduced the volume of pancreatic juice in both basal conditions and after caerulein stimulation. Bombesin increased pancreatic weight as well as the protein and enzymatic contents of the gland. Neither the weight of the pancreas nor its composition were significantly affected by CCK-antagonist proglumide, the putative bombesin antagonist spantide or the H2-receptor antagonist ranitidine. These results show that bombesin has a trophic effect on rat pancreas and concomitantly increases its secretory capacity. Both effects are likely to be mediated through a direct action of the peptide on the pancreatic gland.


Application of the ELDO approach to assess cumulative eye lens doses for interventional cardiologists.
In preparation of a large European epidemiological study on the relation between eye lens dose and the occurrence of lens opacities, the European ELDO project focused on the development of practical methods to estimate retrospectively cumulative eye lens dose for interventional medical professionals exposed to radiation. The present paper applies one of the ELDO approaches, correlating eye lens dose to whole-body doses, to assess cumulative eye lens dose for 14 different Finnish interventional cardiologists for whom annual whole-body dose records were available for their entire working period. The estimated cumulative left and right eye lens dose ranged from 8 to 264 mSv and 6 to 225 mSv, respectively. In addition, calculations showed annual eye lens doses sometimes exceeding the new ICRP annual limit of 20 mSv. The work also highlights the large uncertainties associated with the application of such an approach proving the need for dedicated dosimetry systems in the routine monitoring of the eye lens dose.


Stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production and its role as an autocrine inducer of CD14 upregulation in human myeloid leukemia cells.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that takes part in the growth and differentiation of normal and leukemic hematopoietic cells. Because of its potential significance in the etiopathogenesis of myeloid leukemia, we have studied the extracellular stimuli leading to GM-CSF secretion from a human myeloid leukemia cell line, K-562, and have demonstrated an important role for the cytokine in the differentiation process of this cell line. TNF-alpha, IL-1 beta, phorbol ester (PMA), and calcium ionophore A23187 were found to stimulate GM-CSF production from K-562 cells. PMA caused the cells to differentiate into megakaryocytic lineage, whereas treatment with A23187 resulted in increased expression of monocyte/macrophage marker CD14. Neutralization of the GM-CSF activity in the culture medium, as well as blocking of its receptors, resulted in suppression of the increase in CD14 expression and partially restored the proliferative capacity in cells exposed to A23187. Autocrine GM-CSF secretion did not appear to play an important role in PMA-induced megakaryocytic differentiation. These results suggest that autocrine GM-CSF secretion may be associated with differentiation of myeloid leukemic cells without any significant growth stimulatory activity.


(E,E)-1,2-Bis[4-(prop-2-yn-1-yl-oxy)benzyl-idene]hydrazine.
The mol-ecule of the title compound, C(20)H(16)N(2)O(2), is centrosymmetric with the mid-point of the central N-N bond located on an inversion center. The configuration around the C=N bond is E. The whole mol-ecule (except for the H atoms) is approximately planar, with an r.m.s. deviation of 0.07 Å. In the crystal, the presence of weak inter-molecular C-H⋯O hydrogen bonding involving each acetyl-ene H atom and the adjacent phen-oxy O atom results in the formation of supra-molecular chains.


[Production of tyramine in "moromi" mash during soy sauce fermentation].
The concentrations of 7 non-volatile amines, tyramine (Tym), histamine (Him), phenethylamine (Phm), putrescine (Put), cadaverine (Cad), spermidine (Spd) and spermine (Spm) in the liquid part of "moromi" mash during soy sauce fermentation were studied. These amines, except for him and Cad, were detected during fermentation by the conventional production method in the laboratory. Put and Spd were detected at the beginning, and Tym, Phm and Spm appeared later; these 5 amines increased gradually during the fermentation. Put, Spd, Spm and Cad were present in the raw starting material for soy sauce; thus, Tym and Phm were produced by the fermentation. When "moromi" mash was added to liquid medium and cultivated, Tym was detected in some "moromi" mash and the other amines were not detected. Tym-producing bacterial strains were isolated from the liquid culture media of Tym-positive "moromi" mash. The Tym-producing strain was a gram-positive coccus. The conditions for production of amines by Tym-producing bacterial strains were examined. These strains grew and produced tyramine under various conditions, which may occur during soy sauce fermentation. Namely, Tym was produced at pH 5-10, at salt concentrations of less than 8%, under either aerobic or anaerobic conditions. During soy sauce fermentation, it is assumed that Tym would be produced by these strains during the early stages of soy sauce aging within a short period when the salt concentration and pH conditions are optimal for growth. Based on the bacteriological properties, the strains were identified as Enterococcus faecium. With the exception of Phm and Him, which did not exist in the starting raw material, non-volatile amines (including Put, Cad, Spd and Spm) were not produced and microorganisms producing them are not believed to be present during "moromi" fermentation.


Moving-object segmentation using a foreground history map.
This paper describes a real-time foreground segmentation method in monocular video sequences for video teleconferencing. Background subtraction is widely used in foreground segmentation for static cameras. However, the results are usually not accurate enough for background substitution tasks. In this paper, we propose a novel strategy for fast and accurate foreground segmentation. The strategy consists of two steps: initial foreground segmentation and fine foreground segmentation. The key to our algorithm consists of two steps. In the first step, a moving object is roughly segmented using the background subtraction method. In order to update the initial foreground segmentation results in the second step, a region-based segmentation method and a foreground history map (FHM)-based segmentation representing the combination of temporal and spatial information were developed. The segmentation accuracy of the proposed algorithm was evaluated with respect to the ground truth, which was the manually cropped foreground. The experimental results showed that the proposed algorithm improved the accuracy of segmentation with respect to Horprasert's well-known algorithm.


Cardiovascular Outcomes Among Older Individuals With Depression Prescribed Amphetamines: A Retrospective Cohort Study.
Prescription amphetamines are utilized for treatment of depression in older adults, yet cardiovascular risks in this population are not well described. The purpose of this study is to evaluate risk of cardiovascular events among adults aged 65 and older with depression who were prescribed amphetamines. We conducted a retrospective matched cohort study utilizing the TriNetx database and statistical software. The 1:1 propensity score matching technique was performed using logistic regression to balance the baseline characteristics of the population. Inclusion criteria were a diagnosis of depression and age 65 years and older. We excluded individuals with an adverse cardiovascular event or diagnosis of attention deficit and hyperactivity disorder prior to enrollment. Individuals were followed from January 1, 2018 to December 31, 2020. Those prescribed an amphetamine were considered exposed and others served as controls. We used descriptive statistics and calculated risk ratios to assess the relationship between amphetamine prescriptions and cardiovascular events in these cohorts. There were 4 434 included in the exposed cohort and 4 434 matched controls in the unexposed group. The cohort exposed to amphetamines had higher high-density lipoprotein along with lower low-density lipoprotein, total cholesterol, hemoglobin A1C, systolic blood pressure, and body mass index than the control group, but increased risk of cardiovascular events (risk ratio: 8.9; 95% confidence interval: 6.39, 12.48). Amphetamines offer potential benefits to people with depression; however, these data suggest increased risk of cardiovascular events among older individuals. Additional research is warranted to fully characterize risk among subpopulations of older adults and inform patient-provider decision making.


Variation in the Markers of Nutritional and Oxidative State in a Long-Lived Seabird: Associations with Age and Longevity.
Age-related declines in life-history traits have been widely observed in free-living animals. Several theories link senescence to oxidative stress. The aim of this study was to measure several widely used markers of oxidative and nutritional state in a long-lived seabird, the common gull (Larus canus), in order to assess the suitability of these markers for describing deterioration in physiological condition associated with chronological age and survival. Associations with longevity and individual consistency of these parameters over the years (repeatability) were also assessed. Senescence in fitness parameters was observed during the study period: in females, laying date and clutch mass were related to bird age in a curvilinear manner, with middle-aged birds breeding earlier and laying heavier eggs. The only parameter associated with aging processes was glutathione concentration in erythrocytes, which was lower in female birds with longer life spans. Of indexes of nutritional state, plasma triglyceride concentration showed a between-individual increase with age, suggesting selective mortality of birds with low levels. Additionally, total plasma protein levels of individual males increased with age. The mostly negative results of this study hint that the commonly used parameters of physiological condition and oxidative state used in this study do not adequately reflect an individual's long-term health condition. Alternatively, it is possible that in common gulls, senescence occurs in reproductive mechanisms but not in mechanisms responsible for maintaining an organism's redox balance, consistent with the idea that different aspects of an organism's physiological condition age at different rates. Significant interannual repeatability was detected in three plasma constituents-carotenoids, uric acid, and total protein-all of which can possibly be linked to variation in dietary habits.


Mediterranean diet and depression: a population-based cohort study.
Depression imposes immense public health burden, demonstrating an urgent need of the identification of modifiable risk factors. Only a few cohort studies have analyzed the association between Mediterranean dietary pattern (MDP) and depression but with mixed results. We examined the impact of MDP on clinically ascertained depression in a large population-based dataset. In 1991/92, detailed information on diet, using a food frequency questionnaire, and potential confounding factors (body weight, height, educational attainment, smoking, previous diabetes and hypertension, and physical activity) was collected, in a random sample of 49,261 Swedish women aged 29-49. Adherence to MDP was calculated. Clinical depression was extracted from the National Patient Register. Study participants were followed up through 2012. During an average follow-up of 20.4 years, 1677 incident cases of depression were diagnosed. We observed a lower risk of depression for medium (score 4-5) and high (6-9) adherence to MDP, compared with low (0-3) adherence (Medium: hazard ratio (HR) = 0.90, 95% confidence interval (CI) = 0.81-1.00; High: HR = 0.82, 95%CI = 0.71-0.94). Per unit increase of adherence, the risk of depression was reduced by 5% (HR = 0.95, 95%CI = 0.92-0.98). The association became stronger when restricting to severe form of depression (HR = 0.51, 95%CI = 0.33-0.76). The HRs were higher from age 50 onward both over the first and the second 10-year follow-up period, compared with before age 50, indicating stronger association with increasing age. Results remained after extensive sensitivity analyses. Higher adherence to a Mediterranean diet at middle age was associated with a lower risk of depression later in life among Swedish women.


Recovery from 3 Years of Daily Olfactory Distortions after Short-Term Treatment with GABA-Analogue.
This case report describes a healthy 47-year-old man with a 3 years history of daily unpleasant olfactory distortions with severe negative effects on the quality of life. The distorted smoke-like smell occurred every day and was most prominent in the evenings resulting in severe discomfort as the patient felt suffocated by the smoke when falling asleep. The distorted smell had no odour triggers and was classified as phantosmia. Patient history, nasal endoscopy, neurological and otolaryngological examination, depression screening, cognitive testing, and CT scan revealed no obvious aetiology, resulting in the diagnosis of idiopathic phantosmia. Quantitate olfactory function was normal. Based on anecdotal evidence in the literature, the patient was treated with a GABA-analogue (pregabalin 50 mg × 3) for 4 weeks. During this treatment, the olfactory distortions completely disappeared for the first time in 3 years and had not reoccurred after 7 months of follow-up. GABA-analogues may be a potential treatment for some of the patients suffering from olfactory distortions. While this constitutes a single case report without controls and phantosmia can disappear spontaneously, there is no proof of causality. However, given the long duration of symptoms, temporal relationship with treatment on the sudden disappearance of phantosmia, and long follow-up without recurrence, this highlights the need for further studies on GABA-analogues as a potential treatment of idiopathic phantosmia. Consequently, larger studies and systematic evaluation of potential effects in different patient groups are warranted before routine treatment with GABA-analogues is advised.


[Amyotrophic lateral sclerosis and cognitive disorders: review and analysis of the literature].
In the last ten years, the syndromic nature of amyotrophic lateral sclerosis (ALS) has become more accepted. Together with upper and lower motor neuron signs, sensory or cognitive impairment are not uncommon. The frequency of a multidegenerative profile in ALS with SOD1 mutations is also an argument for this. We reviewed the literature about:


Overexpression of tumor suppressor protein OSCP1/NOR1 induces ER stress and apoptosis during development of Drosophila melanogaster.
OSCP1/NOR1 (organic solute carrier partner 1/oxidored-nitro domain-containing protein 1) is known as a transporter of various organic solutes into cells and also is reported to act as a tumor suppressor protein. Although overexpression of OSCP1 has been shown to play multiple roles in mammalian cell lines, its biological significance in living organisms is not fully understood. To explore the effects of OSCP1/NOR1 on development, we performed genetic studies in flies featuring overexpression of its Drosophila orthologue, dOSCP1. Overexpression of dOSCP1 in eye imaginal discs induced a rough eye phenotype in adult flies, likely resulting from a delay in S phase progression and induction of caspase-dependent apoptosis followed by compensatory proliferation. However, it did not appear to be involved in differentiation of R7 photoreceptor cells. We also found that overexpression of dOSCP1 caused endoplasmic reticulum stress in salivary gland cells. These results indicate that overexpression of dOSCP1 exerts effects on various biological processes during Drosophila development.


Patient reported outcomes: looking beyond the label claim.
The use of patient reported outcome scales in clinical trials conducted by the pharmaceutical industry has become more widespread in recent years. The use of such outcomes is particularly common for products developed to treat chronic, disabling conditions where the intention is not to cure but to ameliorate symptoms, facilitate functioning or, ultimately, to improve quality of life. In such cases, patient reported evidence is increasingly viewed as an essential complement to traditional clinical evidence for establishing a product's competitive advantage in the marketplace. In a commercial setting, the value of patient reported outcomes is viewed largely in terms of their potential for securing a labelling claim in the USA or inclusion in the summary of product characteristics in Europe. Although, the publication of the recent US Food and Drug Administration guidance makes it difficult for companies to make claims in the USA beyond symptom improvements, the value of these outcomes goes beyond satisfying requirements for a label claim. The European regulatory authorities, payers both in the US and Europe, clinicians and patients all play a part in determining both the availability and the pricing of medicinal products and all have an interest in patient-reported data that go beyond just symptoms. The purpose of the current paper is to highlight the potential added value of patient reported outcome data currently collected and held by the industry for these groups.


Interpretable, calibrated neural networks for analysis and understanding of inelastic neutron scattering data.
Deep neural networks (NNs) provide flexible frameworks for learning data representations and functions relating data to other properties and are often claimed to achieve 'super-human' performance in inferring relationships between input data and desired property. In the context of inelastic neutron scattering experiments, however, as in many other scientific scenarios, a number of issues arise: (i) scarcity of labelled experimental data, (ii) lack of uncertainty quantification on results, and (iii) lack of interpretability of the deep NNs. In this work we examine approaches to all three issues. We use simulated data to train a deep NN to distinguish between two possible magnetic exchange models of a half-doped manganite. We apply the recently developed deterministic uncertainty quantification method to provide error estimates for the classification, demonstrating in the process how important realistic representations of instrument resolution in the training data are for reliable estimates on experimental data. Finally we use class activation maps to determine which regions of the spectra are most important for the final classification result reached by the network.


The use of botanicals for health purposes by members of a prepaid health plan.
Interviews were conducted with 100 adults (27 men, 73 women) enrolled in a prepaid medical health plan to investigate their use of botanical remedies. They were asked which of 50 listed herbs they or members of their families had used for health purposes and with what effect; which of 60 listed health problems they had treated with home remedies; and what additional home remedies or alternative health care resources they had used. Over 100 different home remedies were identified, with most considered effective. Individual respondents used from 0 to 33 herbal and plant remedies (Md = 7), some of which have toxic properties. A remedy was reported for almost every health problem listed. Substances most frequently used were aloe vera, honey, peppermint, garlic, eucalyptus, and rose hips; health problems most frequently treated were burns, colds, indigestion, insect bites, insomnia, rashes. Persons who were married, from larger households, of higher socioeconomic status, who had consulted alternative healers, or who had patronized health food stores tended to use home remedies more than their counterparts. Implications for further evaluation of self-care practices are discussed.


The Transition to Fatherhood, Contextual Stress, and Substance Abuse: A Prospective Analysis of Rural, Emerging Adult Black American Men.
Background: Among Black American emerging adult men (∼aged 18-25), the early transition to fatherhood is often marred by numerous contextual stressors related to racial discrimination and socioeconomic instability. The strain of transitioning to fatherhood while experiencing high levels of contextual stress may evidence escalations in substance misuse over time as men may turn to substances to cope with the stress of complex life transitions. However, research examining these associations are scarce. Objective: This study aimed to investigate the influence of contextual stress on the association between fatherhood and substance misuse. Hypotheses were tested using multiple linear regression with 3 waves of data from 476 Black American men aged 19 to 22 at baseline living in resource-poor communities in the rural South. Results: Results demonstrated that fatherhood status was associated, prospectively, with Black American fathers' substance misuse when exposure to contextual stress was high but not low. Conclusions: Findings underscore the need for substance misuse prevention programs to (a) support Black American fathers in coping with race-related stress and (b) integrate robust socioeconomic stability services in order in disrupt patterns of future substance misuse by improving Black American men's experience of the transition to fatherhood.


Investigation into the role of catabolite control protein A in the metabolic regulation of Streptococcus suis serotype 2 using gene expression profile analysis.
Catabolite control protein A (CcpA) serves a key function in the catabolism of Streptococcus suis serotype 2 (S. suis 2) by affecting the biological function and metabolic regulatory mechanisms of this bacterium. The aim of the present study was to identify variations in CcpA expression in S. suis 2 using gene expression profile analysis. Using sequencing and functional analysis, CcpA was demonstrated to play a regulatory role in the expression and regulation of virulence genes, carbon metabolism and immunoregulation in S. suis 2. Gene Ontology and Kyto Encyclopedia of Genes and Genomes analyses indicated that CcpA in S. suis 2 is involved in the regulation of multiple metabolic processes. Furthermore, combined analysis of the transcriptome and metabolite data suggested that metabolites varied due to the modulation of gene expression levels under the influence of CcpA regulation. In addition, metabolic network analysis indicated that CcpA impacted carbon metabolism to a certain extent. Therefore, the present study has provided a more comprehensive analysis of the role of CcpA in the metabolic regulation of S. suis 2, which may facilitate future investigation into this mechanism. Furthermore, the results of the present study provide a foundation for further research into the regulatory function of CcpA and associated metabolic pathways in S. suis 2.


Immunodetection of GLUT1, p63 and phospho-histone H1 in invasive head and neck squamous carcinoma: correlation of immunohistochemical staining patterns with keratinization.
Immunodetection of GLUT1, p63 and phospho-histone H1 in invasive head and neck squamous carcinoma: correlation of immunohistochemical staining patterns with keratinizationAims : To examine invasive head and neck squamous carcinomas for expression of GLUT1, a glucose transporter and marker of increased glucose uptake, glycolytic metabolism and response to tissue hypoxia; p63, a p53 homologue that is a marker of the undifferentiated proliferative basaloid phenotype; and phospho-histone H1, a marker of activation of the cell cycle-promoting cyclin-dependent kinases 1 and 2. Methods : Routinely processed slides from 34 invasive squamous carcinomas, including 25 with intraepithelial components, were immunostained with anti-GLUT1 (Chemicon), anti-p63 (4A4, Santa Cruz), and antiphospho-histone H1 (monoclonal 12D11). Results : In keratinizing carcinomas, all three markers were most commonly immunodetected peripherally, with loss of expression in central keratinized zones. In contrast, in non-keratinizing carcinomas, p63 and phospho-histone H1 expression was most commonly observed throughout tumour nests and anti-GLUT1 stained in a pattern suggestive of hypoxia-induced expression ('antistromal' staining), in which cells at the tumour-stromal interface were GLUT1- and cells in central, perinecrotic zones showed progressive induction of GLUT1. Intraepithelial components also displayed basal and 'antibasal' GLUT1 staining patterns, homologous to the pro- and antistromal patterns in invasive carcinoma; basal patterns in intraepithelial lesions appeared to be more predictive of keratinizing invasive carcinoma and antibasal intraepithelial staining more predictive of non-keratinizing poorly differentiated carcinomas. Conclusions : Keratinizing and non-keratinizing squamous carcinomas differ in expression patterns of GLUT1, p63 and phospho-histone H1. In the former, all three markers were typically suppressed in conjunction with keratinization; in the latter, GLUT1 expression was more likely to occur in a hypoxia-inducible pattern and expression of p63 and phospho-histone H1 was unsuppressed. GLUT1 expression patterns in intraepithelial lesions may be predictive of the differentiation status of the associated invasive carcinoma.


Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers.
FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933) and CA-125 (AUC=0.907) were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800). To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912). Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the detection of ovarian cancer.


Phase transition of a two-dimensional binary spreading model.
We investigated the phase transition behavior of a binary spreading process in two dimensions for different particle diffusion strengths (D). We found that N>2 cluster mean-field approximations must be considered to get consistent singular behavior. The N=3,4 approximations result in a continuous phase transition belonging to a single universality class along the D subset (0,1) phase transition line. Large scale simulations of the particle density confirmed mean-field scaling behavior with logarithmic corrections. This is interpreted as numerical evidence supporting the bosonic field theoretical prediction that the upper critical dimension in this model is d(c)=2. The pair density scales in a similar way but with an additional logarithmic factor to the order parameter. At the D=0 end point of the transition line we found directed percolation criticality.


Sex Differences in Dilated Cardiomyopathy Prognosis.
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain controversial. The present meta-analysis aimed to investigate whether sex plays a role in the outcome of patients with DCM and to provide real-world information on these potential sex differences for physicians and patients.We searched the PubMed, Cochrane, and EMBASE databases for published cohort studies up to February 16, 2020 that reported sex-specific prognostic outcomes (e.g., all-cause mortality; sudden cardiac death (SCD) ) in patients with DCM.Finally, 5 clinical cohort studies with a total of 5,709 patients were included. The results showed that males with DCM had a higher risk of all-cause mortality than females (HR: 1.61, 95% CI: 1.36~1.90; P < 0.00001). Next, the included studies were divided into short-term (< 5 years) and long-term (≥ 5 years) outcome groups by follow-up duration. Males showed a higher risk of all-cause mortality in both subgroups (< 5 years, HR: 1.59, 95% CI: 1.13~2.23; P = 0.008; ≥ 5 years, HR: 1.65, 95% CI: 1.33~2.05; P < 0.00001). In addition, the risks of SCD (HR: 1.80, 95% CI: 1.63~2.61; P = 0.002) and cardiovascular mortality in males (HR: 1.67, 95% CI: 1.25~2.23; P = 0.0005) were higher than those in females.The evidence from the published studies suggested that compared with females, males with DCM had an increased risk of all-cause mortality, cardiovascular mortality, and SCD.


Advances in ultrasound move modality into new fields.
For decades, ultrasound has served as an easy-to-use, noninvasive imaging specialty that yielded results both immediately and cost effectively. In the past, medical imaging technology developers focused solely on building ultrasound systems that delivered excellent images. However, over the last decade, as patient and clinical needs evolved, medical imaging manufacturers found themselves adjusting quickly to build systems to meet new market demands. This shift has spurred tremendous technological advancements and enhanced ultrasound's role in the clinical management of a wide range of disease states, including obesity, diabetes, and breast cancer. Ultrasound has become a leader in delivering ergonomically technologies that take into account the needs of clinicians, making this modality one of the most accommodating when it comes to ensuring the long-term safety of today's sonographer.


Epidemiological analysis of acute respiratory disease (ARD) and characteristics of the influenza epidemic in Bohemia during the season 1986/1987.
The authors analyze the findings of epidemiological and virological surveillance of ARD in Bohemia during the season 1986/1987. In all, 57.5% of the Czech population was affected by acute respiratory disease (ARD). There were 5,950,832 cases reported, 124,444 complications (2.1% of the overall morbidity rate) and 5,374 deaths due to influenza, bronchitis, pneumonia and chronic pulmonary affection. The influenza epidemic commenced during the 48-th calendary week (CW) and lasted 5 weeks till the 52-nd CW. The epidemic was due to an influenza virus strain of the subtype A(H1N1) antigenically related to the drift variant A (Singapore) 6/86. Within an extremely short period of the epidemic, 1,094,865 influenza cases were reported and 22,313 cases of complications. 10.7% of the CSR population were affected during the epidemic in whose etiology noninfluenza respiratory viruses were significantly implicated, especially adenoviruses (41.7%) and the RS virus (26.9%). There was no excessive mortality in the course of the epidemic. The authors discuss the atypical nature of this particular influenza epidemic and the etiological role of respiratory viruses.


Rod-shaped bodies resembling birbeck granule-like structures in endothelial cells of dermal capillaries in generalized granuloma annulare.
A previous study demonstrated that, in generalized granuloma annulare in the epidermis, the Langerhans' cell section area and the number of Langerhans' cell granules or Birbeck granules per cell section were increased, suggesting an active state of these Langerhans' cells. Reexamination by transmission electron microscopy of the same tissue, but in samples also containing dermal tissue, from the same subjects revealed endothelial cells with rod-shaped bodies resembling Birbeck granules or Birbeck granule-like structures. This finding has not been previously described in blood vessels of human skin and is described here.


Numerical Evaluation and Experimental Test on a New Giant Magnetostrictive Transducer with Low Heat Loss Design.
Giant magnetostrictive transducer with micro and nano precision has a wide application prospect in the field of remote sensing. However, excessive heat loss of components could generate during the energy conversion and transfer from electric energy to magnetic energy, and magnetic energy to mechanical energy, thereby affecting its long-term service and also reducing energy utilization. In this paper, a new magnetostrictive transducer is proposed and its excitation coil, internal and external magnetic circuit are optimized from the perspective of reducing heat loss. With the help of theoretical and finite element analysis, the response law between key parameters and heat loss of key components are summarized, which provides a basis for reducing heat loss. Finally, according to the optimization scheme, the prototype is processed, and the temperature rise and dynamic output performance of the transducer are tested by constructing an experimental setup. The results show that the transducer has a low temperature rise and good frequency response characteristics, which can provide support for long-time precise actuation on-orbit.


Mapping the targeted membrane pore formation mechanism by solution NMR: the nisin Z and lipid II interaction in SDS micelles.
Nisin is an example of type-A lantibiotics that contain cyclic lanthionine rings and unusual dehydrated amino acids. Among the numerous pore-forming antimicrobial peptides, type-A lantibiotics form an unique family of post-translationally modified peptides. Via the recognition of cell wall precursor lipid II, nisin has the capacity to form pores against Gram-positive bacteria with an extremely high activity in the nanomolar (nM) range. Here we report a high-resolution NMR spectroscopy study of nisin/lipid II interactions in SDS micelles as a model membrane system in order to elucidate the mechanism of molecular recognition at residue level. The binding to lipid II was studied through (15)N-(1)H HSQC titration, backbone amide proton temperature coefficient analysis, and heteronuclear (15)N[(1)H]-NOE relaxation dynamics experiments. Upon the addition of lipid II, significant changes were monitored in the N-terminal part of nisin. An extremely low amide proton temperature coefficient (Delta delta/Delta T) was found for the amide proton of Ala3 (> -0.1 ppb/K) in the complex form. This suggests tight hydrogen bonding and/or isolation from the bulk solvent for this residue. Large chemical shift perturbations were also observed in the first two rings. In contrast, the C-terminal part of nisin was almost unaffected. This part of the molecule remains flexible and solvent-exposed. On the basis of our results, a multistep pore-forming mechanism is proposed. The N-terminal part of nisin first binds to lipid II, and a subsequent structural rearrangement takes place. The C-terminal part of nisin is possibly responsible for the activation of the pore formation. In light of the emerging antibiotic resistance problems, an understanding of the specific recognition mechanism of nisin with lipid II at the residue specific level may therefore aid in the development of novel antibiotics.


Pediatric ocular rosacea: 2 cases.
To report the clinical course of 2 pediatric ocular rosacea cases with a significant delay until diagnosis. We report 2 interventional case reports. Case 1 is a 10-year-old boy with 2 years of recurrent bilateral blepharitis, repetition chalazion, conjunctival hyperemia, and corneal ulcers, without response to topical antibiotics or topical and systemic steroids. Case 2 is a 9-year-old girl with keratoconjunctivitis and repetition chalazion since she was 2 years old, without improvement after consulting several ophthalmologists and performing several treatments throughout those years. Rapid response to systemic erythromycin with marked improvement of both cases within a few weeks. Ocular rosacea is frequently misdiagnosed, particularly in the pediatric population. To our knowledge, this report demonstrates a case with the longest history before diagnosis (7 years) and another case in which a conjunctival biopsy was performed.


Wolbachia pipientis: bacterial density and unidirectional cytoplasmic incompatibility between infected populations of Aedes albopictus.
Unidirectional cytoplasmic incompatibility is seen when certain Wolbachia-infected insect populations are crossed. Two hypotheses might explain this phenomenon: superinfections with mutually incompatible strains of Wolbachia producing incompatibility when crossed to individuals infected with only a single bacterial strain or, alternatively, a bacterial dosage model, with differences in Wolbachia densities responsible for the incompatibility. A quantitative PCR assay was set up as a general method to compare Wolbachia densities between populations. Using this assay in unidirectionally incompatible stocks of the mosquito Aedes albopictus, we have determined that densities are significantly higher in Houston than in the Mauritius and Koh Samui stocks. This is consistent with a dosage model for the observed crossing patterns, but does not rule out the possibility that superinfection is the primary cause of the incompatibility.


Tissue specificities of tumor induction by aromatic amines.
Certain aryl compounds that have nitrogen substitutions on their ring structures are, following metabolic conversion to reactive derivatives, able to elicit toxic responses by virtue of their modifications of protein and nucleic acid. This group of compounds is often referred to as aromatic amines (AA), although from a structural perspective, compounds that can be converted metabolically to crucial AA derivatives are also capable of producing the same adverse biological effects. These effects include cellular death, mutagenic events and tumor induction. Importantly, in humans, AA can induce tumors in the urinary tract, and possibly other tissues. This contribution addresses the mechanisms by which AA are likely to produce these carcinogenic consequences.


Regulation of primary antibody response in mice by two types of suppressor cells resistant to anti-thy-1 serum treatment.
The anti-SRBC antibody response of normal young adult mice (about 3 months old) was specifically suppressed, when the spleen cells derived from the syngeneic donor mice that had been previously primed with a high dose of SRBC were adoptively transferred at the time of antigenic challenge. The suppression was antigen-specific and was mediated by a fraction of the immune spleen cells which appeared to belong to either B cells or their progeny antibody-forming cells. The differences were observed in the properties of the suppressor cells in terms of the period after the priming and the radiosensitivity; i.e., immune spleen cells taken from the mice which had been immunized with SRBC 5 days earlier were able to suppress only 19S PFC, whereas those taken from the mice which had been immunized 14 days earlier were able to suppress both the 19S and 7S PFC responses, and the former cells were susceptible to 400 R X-rays, but not the latter. These two types of suppressor cells appeared to play an important role in the regulation of the sequential change of 19S and 7S antibodies during the primary immune response.


Antigenotoxic effect of allicin against methyl methanesulphonate induced genotoxic damage.
Allicin, one of the sulfur compounds especially thiosulphonates of garlic (Allium sativum), possesses antioxidant and thioldisulphide exchange activity and is also shown to cause a variety of actions potentially useful for human health. In this investigation we determined its antigenotoxic potential using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) induced by methyl methanesulphonate (MMS) as genotoxic end points both in the presence as well as absence of rat liver microsomal activation system (S9 mix) in cultured human lymphocytes. We tested the effect of 5, 10 and 20 microM of allicin on the damage exerted by 60 microM of MMS. The levels of CAs and SCEs were lowered suggesting an antigenotoxic role of allicin against genotoxic damage both in the presence as well as absence of metabolic activation.


Early pregnancy loss.
Previously called spontaneous abortion, early pregnancy loss (EPL) is the preferred term encompassing threatened abortion, incomplete abortion, complete abortion, and anembryonic pregnancy. EPL has many causes, including chromosomal abnormalities, immunologic and infectious causes, and underlying maternal risk factors. Because many patients present with first-trimester bleeding, clinicians must know the appropriate evaluation and management techniques.


Acute Intestinal Intussusception: Beware of Burkitt's Lymphoma.
Burkitt's lymphoma can show in a variety of ways, and it's frequently identified in children owing to the development of an abdominal tumor. This aggressive, fast growing tumor can induce either indirect symptoms due to pressure phenomena or direct involvement of the intestine lumen, resulting in intestinal obstruction or intussusception. We are reporting a case of intestinal intussusception in a patient with Burkitt's lymphoma.


Fitting double-hit lymphoma into the aggressive lymphoma spectrum: a square peg in a round hole?
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements or both, commonly called double-hit lymphoma (DHL), is an aggressive B-cell lymphoma that is molecularly distinct from diffuse large B-cell lymphoma (DLBCL) and is associated with poor outcomes. Recent advances in the molecular classification of DLBCL have identified distinct subsets, including genetic signatures which correlate with DHL and survival. DHL with concomitant TP53 mutation appears to be associated with a very poor prognosis. Standard chemo-immunotherapy is not an effective treatment for these patients and personalized, innovative strategies are needed. In this review, we summarize recent advances in the subclassification of DLBCL, with a focus on DHL. We also incorporate early, promising clinical trial data using CAR T and targeted therapies. Rationally designed clinical trials for DLBCL are needed to advance the care of patients with DHL and other adverse risk DLBCL subgroups.


Rectum mucinous adenocarcinoma metastasis to bilateral breast in a male patient: A case report.
A 47-year-old male presented to our clinic with complaints of mass in both breasts. In the patient's history, he had undergone low anterior resection for rectum mucinous adenocarcinoma 2 years ago. The masses in both breasts of the patient were excised. Mucinous adenocarcinoma metastases were reported in the pathologic evaluation of the masses. Metastasis should be considered in patients with bilateral breast mass and previously diagnosed cancer even if the patient is male.


Mechanical restraint and characteristics of patient, staff and shifts in a psychiatric ward.
The use of coercion is a balance between depriving the patients' autonomy and dignity and preventing endangerment of the body or health of self or others. It is of importance to obtain more knowledge about mechanisms leading to mechanical restraint in the attempt of reducing it. To analyse for associations between incidence of mechanical restraint (MR) and staffing level, staff demographics, patient characteristics, type of shift (day/evening/night) and change of shifts. A naturalistic descriptive method was used to study cases of MR in a psychiatric ward. Data for each case of MR was obtained from an electronic reporting system. Care workers from each shift were identified using duty rosters. Analyses included binary logistic regression analyses. In 82% of the 114 cases of MR, the patient was diagnosed with personality disorders. In the multiple regression analysis, a significant association was found between the use of MR and the presence of male care workers on the ward (OR:1.44, 95% CI: 1.01-2.05; p = .04). Moreover, MR was associated with evening shifts, compared with day and night shifts (OR =1,29, 95% CI: 1.14-2.57, p = .01). Besides, months from January to December was associated with a decrease in MRs (OR: 0.88, 95% CI: 0.83-0.94; p = 7.3 E-6). No significant associations were found between MR and staffing level or experience. MR was associated with evening shifts, higher number of male care workers on duty and a decrease from January to December.


OsCERK1 and OsRLCK176 play important roles in peptidoglycan and chitin signaling in rice innate immunity.
Microbe-associated molecular pattern (MAMP)-triggered immunity plays critical roles in the basal resistance defense response in plants. Chitin and peptidoglycan (PGN) are major molecular patterns for fungi and bacteria, respectively. Two rice (Oryza sativa) lysin motif-containing proteins, OsLYP4 and OsLYP6, function as receptors that sense bacterial PGN and fungal chitin. These membrane receptors, which lack intracellular kinase domains, likely contain another component for transmembrane immune signal transduction. Here, we demonstrate that the rice LysM receptor-like kinase OsCERK1, a key component of the chitin elicitor signaling pathway, also plays an important role in PGN-triggered immunity in rice. Silencing of OsCERK1 suppressed PGN-induced (and chitin-induced) immunity responses, including reactive oxygen species generation, defense gene expression, and callose deposition, indicating that OsCERK1 is essential for both PGN and chitin signaling initiated by OsLYP4 and OsLYP6. OsLYP4 associated with OsLYP6 and the rice chitin receptor chitin oligosaccharide elicitor-binding protein (CEBiP) in the absence of PGN or chitin, and treatment with PGN or chitin led to their disassociation in vivo. OsCERK1 associated with OsLYP4 or OsLYP6 when induced by PGN but it associated with OsLYP4, OsLYP6, or CEBiP under chitin treatment, suggesting the presence of different patterns of ligand-induced heterooligomeric receptor complexes. Furthermore, the receptor-like cytoplasmic kinase OsRLCK176 functions downstream of OsCERK1 in the PGN and chitin signaling pathways, suggesting that these MAMPs share overlapping intracellular signaling components. Therefore, OsCERK1 plays dual roles in PGN and chitin signaling in rice innate immunity and as an adaptor involved in signal transduction at the plasma membrane in conjunction with OsLYP4 and OsLYP6.


Lactate score predicts survival, immune cell infiltration and response to immunotherapy in breast cancer.
Background: Tumor-derived lactate can modulate the function of infiltrating immune cells to establish an immunosuppressive microenvironment that favors tumor progression. However, possible effects of lactate-related genes (LRGs) on the tumor microenvironment (TME) of breast cancer (BRCA) are still unknown. Methods: LRGs were comprehensively screened from lactate metabolism-related pathways. We correlated the expression of these LRGs with immune cell infiltrating characteristics in the TME and clinicopathological features of patients. We also established a lactate score for quantifying lactate metabolism patterns of cancers and to predict of recurrence-free survival (RFS). Results: We successfully constructed a lactate score that was an independent prognostic factor in BRCA. A low lactate score, which was associated with immune activation with increased CD8+ T cells infiltration levels, indicated an inflamed TME. Consistently, higher expression levels of inhibitory immune checkpoints, including PD-L1, LAG3, CTLA4, and TIM3, as observed from high lactate score subgroup, suggested an immune-desert phenotype as well as poor prognosis. Moreover, a low lactate score predicted the increased chemotherapeutic drug sensitivity and enhanced anti-PD-1 immunotherapy responses. Conclusion: The present study analyzed the potential roles of LRGs in the TME diversity and prognosis. These results will help to improve our understanding of the characteristics of TME immune cell infiltration and guide the development of more effective immunotherapy strategies.


Impact of missing data due to dropouts on estimates of the treatment effect in a randomized trial of antiretroviral therapy for HIV-infected individuals. Canadian HIV Trials Network A002 Study Group.
To evaluate the impact of missing data due to nonrandom dropout on estimates of the effect of treatment on the CD4 count in a clinical trial of antiretroviral therapy for HIV infected individuals. The effect of treatment on CD4 counts in a recent study of continued ZDV versus ddI in HIV-infected individuals was estimated from the observed data and after imputing missing CD4 counts for patients who dropped out of the study. Imputation methods studied were (a) carrying forward the last observed CD4 count, (b) predicting missing CD4 counts from regression models, and (c) assuming that CD4 counts of patients who dropped out declined at a rate of 100 cells per year. Of the 245 patients enrolled in the study, 52% completed the planned 48 weeks of follow-up. Patients with lower CD4 counts were more likely to drop out of the study (RR = 1.77; p = 0.0001). Patients receiving ZDV had a greater tendency to drop out than patients receiving ddI (p = 0.07). Mean CD4 counts calculated after imputing missing data were lower than those obtained from the observed data at all follow-up times for both treatment groups. Imputing CD4 counts with regression models yielded higher estimates of the effect of treatment than were obtained using the observed data. Missing outcome data due to dropouts can result in an underestimation of the treatment effect and overly optimistic statements about the outcome of participants on both treatment arms due to the selective dropout of participants with lower or decreasing CD4 counts. When there are significant dropout rates in randomized trials, imputation is a useful technique to assess the range of plausible values of the treatment effect.


Use of genomic information to exploit genotype-by-environment interactions for body weight of broiler chicken in bio-secure and production environments.
The increase in accuracy of prediction by using genomic information has been well-documented. However, benefits of the use of genomic information and methodology for genetic evaluations are missing when genotype-by-environment interactions (G × E) exist between bio-secure breeding (B) environments and commercial production (C) environments. In this study, we explored (1) G × E interactions for broiler body weight (BW) at weeks 5 and 6, and (2) the benefits of using genomic information for prediction of BW traits when selection candidates were raised and tested in a B environment and close relatives were tested in a C environment. A pedigree-based best linear unbiased prediction (BLUP) multivariate model was used to estimate variance components and predict breeding values (EBV) of BW traits at weeks 5 and 6 measured in B and C environments. A single-step genomic BLUP (ssGBLUP) model that combined pedigree and genomic information was used to predict EBV. Cross-validations were based on correlation, mean difference and regression slope statistics for EBV that were estimated from full and reduced datasets. These statistics are indicators of population accuracy, bias and dispersion of prediction for EBV of traits measured in B and C environments. Validation animals were genotyped and non-genotyped birds in the B environment only. Several indications of G × E interactions due to environmental differences were found for BW traits including significant re-ranking, heterogeneous variances and different heritabilities for BW measured in environments B and C. The genetic correlations between BW traits measured in environments B and C ranged from 0.48 to 0.54. The use of combined pedigree and genomic information increased population accuracy of EBV, and reduced bias of EBV prediction for genotyped birds compared to the use of pedigree information only. A slight increase in accuracy of EBV was also observed for non-genotyped birds, but the bias of EBV prediction increased for non-genotyped birds. The G × E interaction was strong for BW traits of broilers measured in environments B and C. The use of combined pedigree and genomic information increased population accuracy of EBV substantially for genotyped birds in the B environment compared to the use of pedigree information only.


Assessment of the diagnostic accuracy of 18F-FDG PET/CT in prosthetic infective endocarditis and cardiac implantable electronic device infection: comparison of different interpretation criteria.
The diagnosis of prosthetic valve (PV) infective endocarditis (IE) and infection of cardiac implantable electronic devices (CIEDs) remains challenging. The aim of this study was to assess the usefulness of 18F-FDG PET/CT in these patients and analyse the interpretation criteria. We included 41 patients suspected of having IE by the Duke criteria who underwent 18F-FDG PET/CT. The criteria applied for classifying the findings as positive/negative for IE were: (a) visual analysis of only PET images with attenuation-correction (AC PET images); (b) visual analysis of both AC PET images and PET images without AC (NAC PET images); (c) qualitative analysis of NAC PET images; and (d) semiquantitative analysis of AC PET images. 18F-FDG PET/CT was considered positive for IE independently of the intensity and distribution of FDG uptake. The gold standard was the Duke pathological criteria (if tissue was available) or the decision of an endocarditis expert team after a minimum 4 months follow-up. We studied 62 areas with suspicion of IE, 28 areas (45 %) showing definite IE and 34 (55 %) showing possible IE. Visual analysis of only AC PET images showed poor diagnostic accuracy (sensitivity 20 %, specificity 57 %). Visual analysis of both AC PET and NAC PET images showed excellent sensitivity (100 %) and intermediate specificity (73 %), focal uptake being more frequently associated with IE. The accuracy of qualitative analysis of NAC PET images depended on the threshold: the maximum sensitivity, specificity and accuracy achieved were 88 %, 80 %, 84 %, respectively. In the semiquantitative analysis of AC PET images, SUVmax was higher in areas of confirmed IE than in those without IE (∆SUVmax 2.2, p < 0.001). When FDG uptake was twice that in the liver, IE was always confirmed, and SUVmax 5.5 was the optimal threshold for IE diagnosis using ROC curve analysis (area under the curve 0.71). The value of 18F-FDG PET/CT in the diagnosis of suspected IE of PVs and CIEDs is highly dependent on patient preparation and the method used for image interpretation. Based on our results, the best method is to consider a study positive for IE when FDG uptake is present in both AC PET and NAC PET images.


Living with off-pump coronary artery surgery: evolution, development, and clinical potential for coronary heart disease patients.
The enormous progress in interventional cardiology during the last 10 years has resulted in a major change in the spectrum of patients referred for coronary bypass surgery. These patients are older and sicker and frequently have had previous percutaneous coronary interventions. Consequently, cardiac surgery is responding by adding new surgical techniques: off-pump open-chest coronary bypass surgery (OPCAB), minithoracotomy bypass surgery, videothoracoscopic (robotic) procedures, etc. Several registries published to date have proved OPCAB to be safe and clinically effective. Randomized studies and meta-analysis research in this field provide scientific support and suggest that myocardial, renal, and neurological functions, amongst others, are better preserved by OPCAB than by classic techniques that use a cardiopulmonary bypass pump (CPB). Moreover, avoidance of CPB yields significantly reduced oxidative stress and systemic inflammatory response. This results in higher safety for ischemic heart disease patients undergoing revascularization, thus offsetting the propensity to lower costs. The present review examines the physiological advantages and clinical outcomes of this simple mode of myocardial revascularisation and evaluates the wider implications arising from its evolution.


[Effects of transgenic Bt cry1Ab rice on collembolan population in paddy field].
To assess the potential ecological risk of transgenic Bt rice to non-target soil organisms in paddy field, transgenic crylAb rice KMD1 and KMD2 and their parental control rice line XS11 were planted in experimental fields, and collembolan species and their densities were investigated during grain-filling and post-harvest stages in 2003 to approximately 2004. By using an arthropod-sucking machine, two collembolan species, Entomobrya griseoolivata and Bourletiella christianseni, were collected from the leaf litter at soil surface during grain-filling stage (September,2003), and the population densities of E. griseoolivata in KMD1 and KMD2 paddy fields were significantly higher than those in XS11 paddy field. With bags contained rice stem-leaf litter and initially placed in the paddy field at harvest time (November,2003), four collembolan species, E. griseoolivata, B. christianseni, Hypogastrura matura and Isotoma monochaeta, were collected during post-harvest stages (April, 2004), and the densities of E. griseoolivata and H. matura in KMD1 and KMD2 paddy fields were also significantly higher than those in XS11 paddy field. The biomass loss of KMD1 and KMD2 stem-leaf litter was significantly greater than that of XS11's.


Dietary Supplementation With Vitamins and Minerals Improves Larvae and Adult Rearing Conditions of Anopheles darlingi (Diptera: Culicidae).
Several experiments with Anopheles darlingi Root, an important malaria vector in the Amazon region, were carried out in the laboratory, depending on the large-scale production of viable larvae and adults. Certainly, improvements in rearing conditions, including dietary requirements, can strongly affect mosquito production. In order to increase the production of this species in the laboratory, we first supplemented the regular larval diet (TetraMin Tropical Flakes) with different concentrations of vitamins and minerals and recorded several biological variables: survival and larval development time, emergence ratio, and adult longevity under a small-scale rearing condition. Second, we established an experimental design under regular lab-rearing conditions based on the concentration of vitamins and minerals that best contributed to the development of these anophelines, and evaluated the biological parameters already mentioned. Moreover, under regular rearing conditions, we recorded sex ratio, adult size, and longevity of adults fed with supplemented sucrose. The lowest concentration of vitamins (V5) and the average concentration of minerals (M3) increased larval survival and decreased larval development time compared with the control. Under regular rearing conditions, minerals provided higher larval survival and increased the longevity of adults fed with supplemented sucrose. Supplementing the regular larval diet and sucrose solutions with vitamins and minerals increased the production of immatures and the longevity of An. darlingi adults.


What is the role of conventional antidepressants in the treatment of major depressive episodes with Mixed Features Specifier?
The newly introduced Mixed Features Specifier of Major Depressive Episode and Disorder (MDE/MDD) is especially challenging in terms of pharmacological management. Prior to the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the symptoms of the mixed features specifier were intradepressive hypomanic symptoms, always and only associated with bipolar disorder (BD). Intradepressive hypomanic symptoms, mostly referred to as depressive mixed states (DMX), have been poorly characterized, and their treatment offers significant challenges. To understand the diagnostic context of DMX, we trace the nosological changes and collocation of intradepressive hypomanic symptoms, and examine diagnostic and prognostic implications of such mixed features. One of the reasons so little is known about the treatment of DMX is that depressed patients with rapid cycling, substance abuse disorder, and suicidal ideation/attempts are routinely excluded from clinical trials of antidepressants. The exclusion of DMX patients from clinical trials has prevented an assessment of the safety and tolerability of short- and long-term use of antidepressants. Therefore, the generalization of data obtained in clinical trials for unipolar depression to patients with intradepressive hypomanic features is inappropriate and methodologically flawed. A selective review of the literature shows that antidepressants alone have limited efficacy in DMX, but they have the potential to induce, maintain, or worsen mixed features during depressive episodes in BD. On the other hand, preliminary evidence supports the effective use of some atypical antipsychotics in the treatment of DMX.


Interaction between attrition,abrasion and erosion in tooth wear.
Tooth wear is the result of three processes: abrasion (wear produced by interaction between teeth and other materials), attrition (wear through tooth-tooth contact) and erosion (dissolution of hard tissue by acidic substances). A further process (abfraction) might potentiate wear by abrasion and/or erosion. Both clinical and experimental observations show that individual wear mechanisms rarely act alone but interact with each other. The most important interaction is the potentiation of abrasion by erosive damage to the dental hard tissues. This interaction seems to be the major factor in occlusal and cervical wear. The available evidence seems insufficient to establish whether abfraction is an important contributor to tooth wear in vivo. Saliva can modulate erosive/abrasive tooth wear through formation of pellicle and by remineralisation but cannot prevent it.


HOXB3 promotes trophoblast cell proliferation, invasion, and migration to alleviate preeclampsia via mediating the Notch/Wnt/β-catenin pathway.
Preeclampsia (PE) harms a significant number of pregnant women and fetuses. However, because of its complex pathological mechanisms, there is no cure except for delivery. This study identified the impact and mechanisms of action of HOXB3 in PE. The behaviors of HTR-8/SVneo cells were analyzed using a cell counting kit-8, EdU, and transwell assays. The interaction between HOXB3 and Notch1 was assessed using a luciferase reporter and chromatin immunoprecipitation assays. Expression was measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence assays. Additionally, the function of HOXB3 was evaluated in an established rat model of PE. We found that HOXB3 was upregulated in PE. HOXB3 overexpression facilitated trophoblast cell proliferation, migration, and invasion. HOXB3 transcriptionally regulated Notch1 by binding to its promoter. Notch1 knockdown abrogated the functions of HOXB3 and the-catenin pathway in trophoblasts. Suppression of the Wnt/β-catenin pathway abrogated the effects of HOXB3. Additionally, HOXB3 alleviated the symptoms in PE rats. In conclusion, HOXB3 transcriptionally activated Notch1 expression and the-catenin pathway, promoting trophoblast cell proliferation, invasion, and migration, thereby alleviating PE progression. This study provides a novel approach for PE therapy.


Gender and the pattern of transmission of measles infection. A reanalysis of data from the Machakos area, Kenya.
Data on measles from the project in the Machakos district, Kenya between 1974 and 1981 have been reanalysed in order to test the impact of sex and cross-sex transmission on severity of infection. In families with several cases, the case fatality rate was high as 11.3% (13/115) during the initial 6 months of the project. In the remaining period, the case fatality rate fell to 2.4% (21/885) (relative risk (RR) = 0.21, 95% confidence interval (CI): 0.11-0.39). During the initial period with high mortality, second cases had 4.74 times higher mortality (95% CI: 1.65-13.66) than index cases and there was no difference in mortality between girls and boys (RR = 0.98). Among secondary cases, though not significant, those infected by someone of the opposite sex had a trend toward a higher risk of dying than those infected by someone of their own sex (RR = 2.44, 95% CI: 0.77-7.78). In families with two children of the same sex, the case fatality rate was 9% compared with 29% in families with a boy and a girl (RR = 3.49; 95% CI: 0.96-12.75). In the subsequent period with low mortality, the difference in mortality between index and secondary cases was less pronounced (RR = 2.32, 95% CI: 1.03-5.25) and girls had significantly higher case fatality than boys (RR = 2.63, 95% CI: 1.09-6.34). There was no difference in this case fatality rate associated with cross-sex transmission of infection (RR = 0.88).(ABSTRACT TRUNCATED AT 250 WORDS)


Long COVID, neuropsychiatric disorders, psychotropics, present and future.
Long COVID refers to the lingering symptoms which persist or appear after the acute illness. The dominant long COVID symptoms in the two years since the pandemic began (2020-2021) have been depression, anxiety, fatigue, concentration and cognitive impairments with few reports of psychosis. Whether other symptoms will appear later on is not yet known. For example, dopamine-dependent movement disorders generally take many years before first symptoms are seen. Post-stroke depression and anxiety may explain many of the early long COVID cases. Hemorrhagic, hypoxic and inflammatory damages of the central nervous system, unresolved systematic inflammation, metabolic impairment, cerebral vascular accidents such as stroke, hypoxia from pulmonary damages and fibrotic changes are among the major causes of long COVID. Glucose metabolic and hypoxic brain issues likely predispose subjects with pre-existing diabetes, cardiovascular or lung problems to long COVID as well. Preliminary data suggest that psychotropic medications may not be a danger but could instead be beneficial in combating COVID-19 infection. The same is true for diabetes medications such as metformin. Thus, a focus on sigma-1 receptor ligands and glucose metabolism is expected to be useful for new drug development as well as the repurposing of current drugs. The reported protective effects of psychotropics and antihistamines against COVID-19, the earlier reports of reduced number of sigma-1 receptors in post-mortem schizophrenic brains, with many antidepressant and antipsychotic drugs being antihistamines with significant affinity for the sigma-1 receptor, support the role of sigma and histamine receptors in neuroinflammation and viral infections. Literature and data in all these areas are accumulating at a fast rate. We reviewed and discussed the relevant and important literature.


Determinants of kidney function in Swedish families: role of heritable factors.
The aim of this study was to evaluate the determinants of kidney function and the role of heritable factors in a sample of 249 siblings free from known cardiovascular disease and without antihypertensive drugs belonging to 110 families. Four different measures and estimates of kidney function were considered. Blood pressure was recorded during 24 h by ambulatory blood pressure monitoring. Heritability was estimated with and without adjustment for significant covariates.In multivariate analysis, in addition to age, sex, BMI, HDL-cholesterol, 24-h systolic and mean blood pressure, systolic nocturnal blood pressure dipping resulted independently related to serum creatinine, estimated Cockcroft-Gault-creatinine clearance and estimated by the modification of diet in renal disease-glomerular filtration rate. After full adjustment, the heritability values were 51% for the measured creatinine clearance (P < 0.01), 58% for the estimated Cockcroft-Gault-creatinine clearance (P < 0.001), 40% for the estimated by the modification of diet in renal disease-glomerular filtration rate (P < 0.001), but 8% (P = 0.34) for serum creatinine.Our data confirm that kidney function is partially under genetic control and that genetic variants of importance for this trait could be mapped. The association of the circadian rhythm of blood pressure with kidney function in this sample deserves further investigation.


The register-based system of demographic and social statistics in Denmark.
"Denmark has developed a statistical system where a large portion of official statistics is based on administrative registers. Population and Housing Censuses have been replaced by register based statistics since 1981. The key of the system is the unique Person Number used in all public administrations. A large number of registers is used as sources and is linked together in order to compile the best estimates of the statistical concepts. This allows for high quality statistics that are timely, consistent and well-suited for longitudinal studies. Problems of quality may arise from changes in the legislation or in the registers. A strong data protection policy is necessary in order to preserve the system."


σ Models on Quantum Computers.
We formulate a discretization of σ models suitable for simulation by quantum computers. Space is substituted with a lattice, as usually done in lattice field theory, while the target space (a sphere) is replaced by the "fuzzy sphere", a construction well known from noncommutative geometry. Contrary to more naive discretizations of the sphere, in this construction the exact O(3) symmetry is maintained, which suggests that the discretized model is in the same universality class as the continuum model. That would allow for continuum results to be obtained for very rough discretizations of the target space as long as the space discretization is made fine enough. The cost of performing time evolution, measured as the number of controlled-not operations necessary, is 12LT/Δt, where L is the number of spatial sites, T the maximum time extent, and Δt the time spacing.


Self-Replicating Catalyzed Hairpin Assembly for Rapid Signal Amplification.
A rapid signal amplification system based on the self-replicating catalyzed hairpin assembly is reported in which two hairpins, H1 and H2, were well-designed in which two split target/trigger DNA and two split G-quadruplex sequences were respectively integrated into H1 and H2. Target/trigger DNA can be cyclically used in this system to form the duplex DNA assemblies (H1-H2), which will bring the two G-quadruplex fragments into close-enough proximity to induce the formation of intact G-quadruplex as a colorimetric signal readout. Similarly, the two split target/trigger DNA sequences will reunite into a DNA sequence that is identical to the target/trigger DNA; then, the obtained replica can also be cyclically used as a new activator unit to trigger the CHA reaction, leading to the rapidly and significantly enhanced formation of target/trigger DNA replicas with the concomitant generation of a higher signal. This self-replication-based autocatalytic signal amplified approach has been successfully used to develop a rapid and visual assay for DNA and small molecule detection.