Correlates of Healthy Eating in Urban Food Desert Communities.
The food environment is well documented as an important emphasis for public health intervention. While theoretical models of the relationship between the food environment and dietary outcomes have been proposed, empirical testing of conceptual models has been limited. The purpose of this study was to explore which factors in nutrition environments are significantly associated with dietary outcomes in two urban, low-income, and minority food desert communities. This study analyzed cross-sectional data based on 796 participants from the Food in Our Neighborhood Study. Participants were recruited based on a random sample of addresses in neighborhood study areas, Philadelphia, PA (n = 393) and Trenton, NJ (n = 403). Main dietary outcomes were Healthy Eating Index (HEI) scores and fruit and vegetable consumption subscores computed from ASA24® assessments. Exploratory factor analysis was conducted and yielded a model of four factors with 22 items. Among four factors that emerged, three factors (Perceptions of Neighborhood Food Availability; and Household Food Challenges) were significantly correlated with dietary outcomes. My Store's Quality and Perceptions of Neighborhood Food Availability were positively correlated with vegetable consumption subscore. The Household Food Challenges factor was negatively correlated with both vegetable subscore and overall HEI score (i.e., more household challenges were associated with lower dietary scores). These findings confirmed the importance of perceived nutrition environments and household food challenges in predicting dietary outcomes among residents of two urban, low-income, and minority food desert communities.


Socioeconomic factors and mortality in patients with atrial fibrillation-a cohort study in Swedish primary care.
Preventing ischaemic stroke attracts significant focus in atrial fibrillation (AF) cases. Less is known on the association between socioeconomic factors and mortality and cardiovascular outcomes in patients with AF. Our study population included adults (n=12 283) ≥45 years diagnosed with AF at 75 primary care centres in Sweden 2001-07. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between the exposures educational level, marital status, neighbourhood socioeconomic status and the outcomes all-cause mortality, after adjustment for age, and comorbid cardiovascular conditions. During a mean of 5.8 years (SD 2.4) of follow-up, 3954 (32.3%) patients had died; 1971 were women (35.0%) and 1983 were men (29.8%). Higher educational level was associated with a reduced mortality in fully adjusted models: HR 0.85 (95% CI 0.77-0.96) for secondary school in men, HR 0.73 (95% CI 0.60-0.88) for college/university in women, and HR 0.82 (95% CI 0.71-0.94) for college/university in men, compared to primary school. Unmarried men and divorced men had an increased risk of death, compared with married men: HR 1.25 (95% CI 1.05-1.50), and HR 1.23 (95% CI 1.07-1.42), respectively. College/university education level was also associated with lower risk of myocardial infarction in men and women, and lower risk of congestive heart failure in women. More attention could be paid to individuals of lower levels of formal education, and unmarried men, in order to provide timely management for AF and prevent its debilitating complications.


Analysis of length-biased and partly interval-censored survival data with mismeasured covariates.
In this paper, we analyze the length-biased and partly interval-censored data, whose challenges primarily come from biased sampling and interfere induced by interval censoring. Unlike existing methods that focus on low-dimensional data and assume the covariates to be precisely measured, sometimes researchers may encounter high-dimensional data subject to measurement error, which are ubiquitous in applications and make estimation unreliable. To address those challenges, we explore a valid inference method for handling high-dimensional length-biased and interval-censored survival data with measurement error in covariates under the accelerated failure time model. We primarily employ the SIMEX method to correct for measurement error effects and propose the boosting procedure to do variable selection and estimation. The proposed method is able to handle the case that the dimension of covariates is larger than the sample size and enjoys appealing features that the distributions of the covariates are left unspecified.


Role of FDG PET/CT in monitoring treatment response in patients with invasive fungal infections.
Invasive fungal infections (IFIs) occur mostly in immunosuppressed patients and can be life-threatening. Inadequate treatment is associated with high morbidity and mortality. We examined the role of 2-fluorodeoxyglucose positron emission tomography integrated with CT (FDG-PET/CT) in monitoring IFIs and therapy decision-making, and evaluated the role of baseline metabolic parameters in predicting the metabolic response. All patients between October 2009 and March 2018, diagnosed with IFIs, treated with antifungal drugs, and who underwent FDG-PET/CT at baseline and at one or more timepoints during treatment were retrospectively included. The electronic patient files were reviewed for pathology, microbiology, and laboratory findings. All FDG-PET/CT scans were performed according to standardized European Association of Nuclear Medicine/EANM Research Limited (EANM/EARL) protocols. For each scan, the global total lesion glycolysis (TLG) and metabolic volume (MV), highest maximum standardized uptake value (SUVmax), and peak standardized uptake value (SUVpeak) were determined. The role of FDG-PET/CT on monitoring antifungal therapy was assessed by looking at the clinical decision made as result of the scan. Furthermore, the added value of the baseline metabolic parameters in predicting metabolic response to the antifungal treatment was evaluated. Twenty-eight patients with in total 98 FDG-PET/CT scans were included with a mean age of 43 ± 22 years. FDG-PET/CT altered management in 14 out of the 28 patients (50%). At the final FDG-PET/CT scan, 19 (68%) had a complete metabolic response (CMR), seven a partial response and two patients were defined as having progressive disease. Using receiver operative analysis, the cut-off value, sensitivity, specificity, and significance for the baseline TLG and MV to discriminate patients with CMR were 160, 94%, 100%, p < 0.001 and 60, 84%, 75%, p = 0.001 respectively. FDG-PET/CT is useful in the monitoring of IFIs resulting in management therapy change in half of the patients. Baseline TLG and MV were found to be able to predict the metabolic response to antifungal treatment.


The effects of dietary carotenoid intake on carotenoid accumulation in the retina of a wild bird, the house finch (Carpodacus mexicanus).
Carotenoid pigments accumulate in the retinas of many animals, including humans, where they play an important role in visual health and performance. Recently, birds have emerged as a model system for studying the mechanisms and functions of carotenoid accumulation in the retina. However, these studies have been limited to a small number of domesticated species, and the effects of dietary carotenoid access on retinal carotenoid accumulation have not been investigated in any wild animal species. The purpose of our studies was to examine how variation in dietary carotenoid types and levels affect retinal accumulation in house finches (Carpodacus mexicanus), a common and colorful North American songbird. We carried out three 8-week studies with wild-caught captive birds: (1) we tracked the rate of retinal carotenoid depletion, compared to other body tissues, on a very low-carotenoid diet, (2) we supplemented birds with two common dietary carotenoids (lutein + zeaxanthin) and measured the effect on retinal accumulation, and (3) we separately supplemented birds with high levels of zeaxanthin--an important dietary precursor for retinal carotenoids--or astaxanthin--a dominant retinal carotenoid not commonly found in the diet (i.e. a metabolic derivative). We found that carotenoids depleted slowly from the retina compared to other tissues, with a significant (~50%) decline observed only after 8 weeks on a very low-carotenoid diet. Supplementation with lutein + zeaxanthin or zeaxanthin alone significantly increased only retinal galloxanthin and ε-carotene levels, while other carotenoid types in the retina remained unaffected. Concentrations of retinal astaxanthin were unaffected by direct dietary supplementation with astaxanthin. These results suggest highly specific mechanisms of retinal carotenoid metabolism and accumulation, as well as differential rates of turnover among retinal carotenoid types, all of which have important implications for visual health maintenance and interventions.


Life chance characteristics of older users of Swedish massage.
The characteristics of those who use complementary and alternative medicine (CAM), as an approach to chronic disease management, are poorly understood. They may however be important to nurses and other health professionals given that CAM is increasingly used by their patients with chronic disorders. In these contexts, the purpose of this study was to ascertain unique life chance population characteristics which significantly influence the use of Swedish massage therapy (SMT), a popular form of CAM, by older adults with chronic health dysfunctions. A multi-site and cross-sectional design was used, as well as a pre-tested postal questionnaire. One hundred forty-one (141) urban, non-institutionalized, English-speaking older persons participated, ranging in age from 60 to 94 years. Findings denote the essential role life chances have on individuals accessing alternative forms of care.


An Introduction to Epitope Mapping.
Antibodies are protein molecules used routinely for therapeutic, diagnostic, and research purposes due to their exquisite ability to selectively recognize and bind a given antigen. The particular area of the antigen recognized by the antibody is called the epitope, and for proteinaceous antigens the epitope can be of complex nature. Information about the binding epitope of an antibody can provide important mechanistic insights and indicate for what applications an antibody might be useful. Therefore, a variety of epitope mapping techniques have been developed to localize such regions. Although the real picture is even more complex, epitopes in protein antigens are broadly grouped into linear or discontinuous epitopes depending on the positioning of the epitope residues in the antigen sequence and the requirement of structure. Specialized methods for mapping of the two different classes of epitopes, using high-throughput or high-resolution methods, have been developed. While different in their detail, all of the experimental methods rely on assessing the binding of the antibody to the antigen or a set of antigen mimics. Early approaches utilizing sets of truncated proteins, small numbers of synthesized peptides, and structural analyses of antibody-antigen complexes have been significantly refined. Current state-of-the-art methods involve combinations of mutational scanning, protein display, and high-throughput screening in conjunction with bioinformatic analyses of large datasets.


Criminal activities of the elderly in Turkey during the years 2000-2005.
The aging of the population is one of the most important demographic events of the 21st century. The aim of this study is to define the basic variables related with criminal behavior among the elderly for cases over 60 years. A retrospective assessment of the criminal data (255 cases) consists of the period between 2000 and 2005 of the Council of Forensic Medicine, Turkish Ministry of Justice. Of the cases whose average age is 68.2±6.9, 25 of the 56 cases were diagnosed as ill. Out of 225 elderly who had committed a criminal act 56 of them had a medical antecedent which is a psychiatric diagnosis. Whether or not they had a medical antecedent the Board made 90 psychiatric diagnosis. This comprised of 25 out of the 56 who also had a medical antecedent and 65 out of the 199 who did not have a medical antecedent. Delusional disorder (43.3%) and schizophrenia (25.6%) are the most frequent diagnoses. Specializing and developing standards for determining the criminal responsibility of the elderly is required.


Investigating the causal relationship between employment and informal caregiving of the elderly.
Examining the causal relationship between employment and informal caring to date has been impeded in countries like Ireland where there is a lack of suitable panel data and/or variables for instrument construction. This paper employs propensity score matching to control for non-random selection into treatment and control groups which controls for differences in employment outcomes between carers and non-carers in Ireland using data from Quarterly National Household Survey 2009 Quarter 3. Earlier papers focus on using regression techniques which may lead to biased estimates. Results suggest that differences exist between carers and non-carers with respect to their employment status in Ireland. Overall the results suggest that the effects are more significant for those providing greater hours of informal care per week than those providing fewer hours of care per week. The effects estimated in this paper are likely to be more precise as failing to account for potential biases in the relationship are likely to underestimate the true effect of caring on employment outcomes. We find that propensity score matching provides an alternative method of examining the relationship when suitable panel data and/or variables for instrument construction are not available.


Production of perdeuterated fucose from glyco-engineered bacteria.
l-Fucose and l-fucose-containing polysaccharides, glycoproteins or glycolipids play an important role in a variety of biological processes. l-Fucose-containing glycoconjugates have been implicated in many diseases including cancer and rheumatoid arthritis. Interest in fucose and its derivatives is growing in cancer research, glyco-immunology, and the study of host-pathogen interactions. l-Fucose can be extracted from bacterial and algal polysaccharides or produced (bio)synthetically. While deuterated glucose and galactose are available, and are of high interest for metabolic studies and biophysical studies, deuterated fucose is not easily available. Here, we describe the production of perdeuterated l-fucose, using glyco-engineered Escherichia coli in a bioreactor with the use of a deuterium oxide-based growth medium and a deuterated carbon source. The final yield was 0.2 g L-1 of deuterated sugar, which was fully characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. We anticipate that the perdeuterated fucose produced in this way will have numerous applications in structural biology where techniques such as NMR, solution neutron scattering and neutron crystallography are widely used. In the case of neutron macromolecular crystallography, the availability of perdeuterated fucose can be exploited in identifying the details of its interaction with protein receptors and notably the hydrogen bonding network around the carbohydrate binding site.


Generalizing Prototype Theory: A Formal Quantum Framework.
Theories of natural language and concepts have been unable to model the flexibility, creativity, context-dependence, and emergence, exhibited by words, concepts and their combinations. The mathematical formalism of quantum theory has instead been successful in capturing these phenomena such as graded membership, situational meaning, composition of categories, and also more complex decision making situations, which cannot be modeled in traditional probabilistic approaches. We show how a formal quantum approach to concepts and their combinations can provide a powerful extension of prototype theory. We explain how prototypes can interfere in conceptual combinations as a consequence of their contextual interactions, and provide an illustration of this using an intuitive wave-like diagram. This quantum-conceptual approach gives new life to original prototype theory, without however making it a privileged concept theory, as we explain at the end of our paper.


The role of oxidative DNA damage, DNA repair, GSTM1, SOD2 and OGG1 polymorphisms in individual susceptibility to Barrett's esophagus.
Determination of the genetic alterations, which play a role in the etiology of Barrett's esophagus (BE), could help identify high-risk individuals for esophageal adenocarcinoma (EA). The aim of the present study was to investigate the role of oxidative DNA damage, glutathione (GSH) concentration as oxidative stress parameters and DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms as individual susceptibility parameters in the etiology of BE. The study groups comprised BE patients who were clinically diagnosed (n = 40) and a healthy control group (n = 40). Basal DNA damage, pyrimidine and purine base damage after H(2)O(2) induction, H( 2)O(2) sensitivity, DNA repair capacity, oxidized pyrimidine and purine base damage repair were evaluated in peripheral blood lymphocytes with a modified comet assay using specific endonucleases (Endo III and Fpg). Polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based assays were used for genotyping. The patient group showed elevated levels of basal DNA damage, pyrimidine base damage and H(2)O(2) sensitivity as compared to controls (p < .05). DNA repair capacity, oxidized pyrimidine and purine base damage repair capacity, were not statistically different between patients and controls. GSH concentration was found to be significantly lower in smoking patients than in the controls (p < .05). None of the genetic variations changed the risk of having BE disease. However, patients carrying the variant OGG1 Cys allele showed elevated levels of pyrimidine base damage as compared to patients carrying the wild-type OGG1 Ser (p < .05). The results of this study point to a role of oxidative DNA damage in BE. However, DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms appeared to play no role in the individual susceptibility to this disease.


Stress and coping among police personnel in South India.
Police personnel experience the highest levels of stress due to the nature and demands of work. Though many researchers have studied these variables quantitatively, there is a lack of qualitative study, particularly in India. A qualitative study has been carried out to explore the stress and coping strategies of police personnel. This study conducted in-depth interviews with ten police personnel and three focus group discussions with 22 police personnel. Thematic analysis revealed five themes: family stressor, personal stressor, work stressor, and adaptive and maladaptive coping. Inability to take leave, multi-tasking, unscheduled excessive working hours, inability to spend time with the family members, and lack of basic amenities to meet personal hygiene were significant factors for their high level of stress. The results reinforce the need for mitigating the impact of stress by using positive coping strategies and social support resources, which could be achieved through capacity building and mental health programs.


Characterization and isolation of thyroid microsomal antigen.
We investigated the structure of the 107-kD thyroid protein recognized as microsomal antigen. Solubilized microsomes were incubated with affinity gels consisting of IgG, from thyroiditis patients or controls, linked to Reacti-gel. Eluates were analyzed by SDS polyacrylamide electrophoresis and Western blot. 107- and 101-kD proteins were augmented in eluates from gels containing patient IgG and had microsomal antigenicity. In a Western blot of microsomes run under unreduced conditions, poorly defined large proteins were identified by antibody. When eluted electrophoretically and reanalyzed in reducing conditions, they demonstrated the 107-kD antigen. The 107-kD protein identified in reducing conditions was extracted and reanalyzed under nonreducing conditions. Large molecular mass proteins were then observed. On two-dimensional electrophoresis, a 107-kD antigen was isolated with isoelectric point of 7.0. The microsomal antigen may be complexes or multimers of a 107-kD peptide with isoelectric point of 7.0.


Skeletal myogenesis in the zebrafish and its implications for muscle disease modelling.
Current evidence indicates that post-embryonic muscle growth and regeneration in amniotes is mediated almost entirely by stem cells derived from muscle progenitor cells (MPCs), known as satellite cells. Exhaustion and impairment of satellite cell activity is involved in the severe muscle loss associated with degenerative muscle diseases such as Muscular Dystrophies and is the main cause of age-associated muscle wasting. Understanding the molecular and cellular basis of satellite cell function in muscle generation and regeneration (myogenesis) is critical to the broader goal of developing treatments that may ameliorate such conditions. Considerable knowledge exists regarding the embryonic stages of amniote myogenesis. Much less is known about how post-embryonic amniote myogenesis proceeds, how adult myogenesis relates to embryonic myogenesis on a cellular or genetic level. Of the studies focusing on post-embryonic amniote myogenesis, most are post-mortem and in vitro analyses, precluding the understanding of cellular behaviours and genetic mechanisms in an undisturbed in vivo setting. Zebrafish are optically clear throughout much of their post-embryonic development, facilitating their use in live imaging of cellular processes. Zebrafish also possess a compartment of MPCs, which appear similar to satellite cells and persist throughout the post-embryonic development of the fish, permitting their use in examining the contribution of these cells to muscle tissue growth and regeneration.


[Steroid treatment of shock lung--tune for re-evaluation?].
The acute respiratory distress syndrome (ARDS) is one consequence of the body's systemic inflammatory response to a variety of powerful external stimuli. Glucocorticosteroids are highly effective anti-inflammatory drugs. During the last few years, the molecular mechanisms for their mode of action have been revealed; this has prompted a new wave of interest in corticosteroid treatment of systemic inflammatory states. Several clinical studies have been launched; the results have so far been promising. We briefly discuss how new knowledge in this field may influence the use of corticosteroids in the treatment of ARDS. The presentation is illustrated by a case study. The patient was a 15-year-old boy with life-threatening and therapy-resistant ARDS. He was treated in a respirator in an intensive care unit (ICU). Two weeks after admission to the ICU, his situation was desperate. High-dose corticosteroids were instituted, and during a five days' treatment his condition improved dramatically. After discontinuation of glucocorticoids he made further progress and was discharged from the ICU after another eleven days. In this particular patient, administration of glucocorticoids had a striking effect. The influence of glucocorticoids on the activation of the transcription factor NF-kappa B and a resulting reduced synthesis of a number of key inflammatory molecules may be one explanation for the positive course.


The versatility of azelaic acid in dermatology.
Azelaic acid has numerous pharmacological uses in dermatology. Its anti-inflammatory and anti-oxidant properties are thought to correlate with its efficacy in papulopustular rosacea and acne vulgaris, amongst other cutaneous conditions. We conducted a review of the literature on the use of azelaic acid in dermatology using key terms 'acne', 'azelaic acid', 'dermatology', 'melasma', 'rosacea', searching databases such as MEDLINE, EMBASE and PubMed. Only articles in English were chosen. The level of evidence was evaluated and selected accordingly listing the studies with the highest level of evidence first using the Oxford Center of Evidence-Based Medicine 2011 guidance.This review found the strongest evidence supporting the use of azelaic acid in rosacea, followed by its use off-label in melasma followed by acne vulgaris. Weaker evidence is currently available to support the use of azelaic acid in several other conditions such as hidradenitis suppurativa, keratosis pilaris and male androgenic alopecia.Azelaic acid, as a monotherapy or in combination, could be an effective first-line or alternative treatment, which is well-tolerated and safe for a range of dermatological conditions.


Mental health referrals to the Falkland Islands British Military Mental Health Team, 1986-96.
To examine the pattern of out-patient mental health care referrals for military personnel deployed to the Falklands Islands, 1986-96. Data from referral books of British Military Community Mental Health Nurses based in the Falkland Islands were abstracted, entered into an electronic database and analysed. Over the period 1986-96, 538 Service personnel were referred to the mental health out-patient facility on the Falkland Islands. The majority were male (96%) and junior ranks (81%). Approximately a third of patients were referred for reasons relating to alcohol (31%) and for over two-thirds of patients no follow-up was required (68%). Differences were observed by Service with the Army having more referrals due to alcohol than the other two Services, whilst the Navy had more deliberate self-harm referrals and the RAF more referrals for anxiety. The lack of information on the total population deployed to the Falkland Islands over this period limits the interpretation of the results.


Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype.
Osteonectin is recognised as a marker of metastasis progression in melanoma and has been implicated in the transition from radial to vertical growth phase. A Tetracycline-inducible system was used to regulate Osteonectin protein levels in melanoma cell lines to examine the morphological, biochemical and invasive changes that accompany its altered expression. Assay of protein and phosphorylation changes showed a downregulation of E-cadherin, upregulation of Osteopontin and a corresponding increase in phosphorylation of Focal Adhesion Kinase on Tyr(397) and Tyr(576) concomitant with Osteonectin induction. Melanoma cells overexpressing Osteonectin displayed increased invasive potential, whereas ablation of Osteonectin gene transcription using siRNA suppressed the invasive potential of these cells and resulted in the upregulation of E-cadherin. The recently described interaction of Osteonectin with Integrin Linked Kinase leading to modulation of its activity suggests a mechanism relevant to the loss of E-cadherin and cell adhesion that occurs during melanoma progression. These results indicate a central role for Osteonectin in the regulation of gene expression changes driving the progression of melanoma toward metastasis.


Reflectance According to Cell Size, Foaming Ratio and Refractive Index of Microcellular Foamed Amorphous Polymer.
Microcellular foamed plastic has a cell size of approximately 0.1 to 10 microns inside a foamed polymer and a cell density in the range of 109 to 1015 cells/cm3. Typically, the formation of numerous uniform cells inside a polymer can be effectively used for various purposes, such as lightweight materials, insulation and sound absorbing materials. However, it has recently been reported that these dense cell structures, which are induced through microcellular foaming, can affect the light passing through the medium, which affects the haze and permeability and causes the diffused reflection of light to achieve high diffuse reflectivity. In this study, the effects of cell size, foaming ratio and refractive index on the optical performance were investigated by applying the microcellular foaming process to three types of amorphous polymer materials. Thus, this study experimentally confirmed that the advantages of porous materials can be implemented as optical properties by providing a high specific surface area as a small and uniform cell formed by inducing a high foaming ratio through a microcellular foaming process.


[Triple hepatectomy for cancer].
The resection of the metastases from digestive malignant lesions are always the most efficient treatment, if it is complete. However it must be performed without major operative risk. According to this point of view, it is logical to examine the feasibility of three successive hepatectomies for metastases. We report in this study our experience with five cases of triple hepatectomies performed for 4 colic cancers and 1 carcinoid cancer. Two major hepatectomies were performed during this third resection. The re-exposure of the liver was very difficult in 4 cases, and the texture of the liver parenchyma was flabby and abnormal in 5 cases (confirmed with the histologic study). The mean duration of the surgery was 307 minutes, the mean duration of the intermittent pedicle clamping was 59 minutes, and the mean blood loss was 1710 ml. No post-operative death occurred, and the morbidity was low. This 5 third hepatectomies have been compared, for the feasability, to the 41 second hepatectomies and to the 234 first hepatectomies which we have performed. In proportion as hepatectomies are carried out, the difficulties to expose the liver increase, the texture of the liver parenchyma gets spoiled and the duration of the operation increases. In conclusion, the third hepatectomies are technically difficult to perform, but they are feasable. However it is too early to be able to define their indications.


Zwitterionic Silane Copolymer for Ultra-Stable and Bright Biomolecular Probes Based on Fluorescent Quantum Dot Nanoclusters.
Fluorescent semiconductor quantum dots (QDs) exhibit several unique properties that make them suitable candidates for biomolecular sensing, including high brightness, photostability, broad excitation, and narrow emission spectra. Assembling these QDs into robust and functionalizable nanosized clusters (QD-NSCs) can provide fluorescent probes that are several orders of magnitude brighter than individual QDs, thus allowing an even greater sensitivity of detection with simplified instrumentation. However, the formation of compact, antifouling, functionalizable, and stable QD-NSCs remains a challenging task, especially for a use at ultralow concentrations for single-molecule detection. Here, we describe the development of fluorescent QD-NSCs envisioned as a tool for fast and sensitive biomolecular recognition. First, QDs were assembled into very compact 100-150 nm diameter spherical aggregates; the final QD-NSCs were obtained by growing a cross-linked silica shell around these aggregates. Hydrolytic stability in several concentration and pH conditions is a key requirement for a potential and efficient single-molecule detection tool. However, the hydrolysis of Si-O-Si bonds leads to desorption of monosilane-based surface groups at very low silica concentrations or in a slightly basic medium. Thus, we designed a novel multidentate copolymer composed of multiple silane as well as zwitterionic monomers. Coating silica beads with this multidentate copolymer provided a robust surface chemistry that was demonstrated to be stable against hydrolysis, even at low concentrations. Copolymer-coated silica beads also showed low fouling properties and high colloidal stability in saline solutions. Furthermore, incorporation of additional azido-monomers enabled easy functionalization of QD-NSCs using copper-free bio-orthogonal cyclooctyne-azide click chemistry, as demonstrated by a biotin-streptavidin affinity test.


Gyroscopes and the Chemical Literature, 2002-2020: Approaches to a Nascent Family of Molecular Devices.
Research directed toward the goal of molecular gyroscopes since the coverage of a previous review (2002) is described. Such species are a subclass of molecular rotors, which are comprised of rotators and stators. Major categories include (1) systems in which a rotator is embedded in a cage-like stator reminiscent of mechanical toy gyroscopes and (2) molecules that have been engineered to crystallize with parallel rotators and voids or other features that enable the rotator to rotate in the solid state (amphidynamic crystals). Particular attention is given to structural data and strategies for the minimization of rotational barriers. Synthetic routes are also described. Some allied types of molecules and supramolecular assemblies are also treated.


Electrophysiological basis of excitation of canine colonic circular muscle by cholinergic agents and substance P.
The circular muscle layer of the canine colon exhibits omnipresent rhythmic periodic waves of depolarization (slow waves), acting as pacemaker activity. The electrophysiological and motor responses of this layer to the muscarinic agonists acetylcholine and carbachol, and to the excitatory peptide substance P, were studied using the sucrose-gap technique. In addition, changes in the contractile activity were examined in organ bath experiments. The slow waves consisted of an initial potential followed by a plateau potential. All substances depolarized the membrane and increased dramatically the duration of the plateau potential resulting in a decrease of the slow wave frequency. In addition, the amplitude of the plateau potential was often increased significantly. Carbachol and substance P readily evoked spiking activity whereas acetylcholine did not. Both spiking activity and the plateau potential generated contractile activity. The prolongation of the slow wave duration caused a profound alteration of the pattern of contractions. Long-lasting tachyphylaxis to the effect of substance P, but not to acetylcholine or carbachol, occurred. The electrophysiological and motor effects of the drugs were due to a direct action on the smooth muscle cell membrane. This study provides an electrophysiological basis for prolonged circular muscle contractions of the colon, and it emphasizes the pacemaker activity of gastrointestinal smooth muscle as an important site of drug action.


Identification of tumor antigens and immune subtypes of glioma for mRNA vaccine development.
Recent evidence suggested that the mRNA vaccine has been effective for many tumors, but its progress in gliomas was slow. In this study, we screened potential tumor antigens and suitable populations for mRNA vaccine to develop mRNA vaccine for glioma. We integrated the normalized RNA sequencing expression data and somatic mutation data from TCGA-GBM, TCGA-LGG, and CGGA datasets. Putative antigens in glioma were identified by selecting highly mutated genes with intimate correlation with clinical survival and immune infiltration. An unsupervised partition around medoids algorithm was utilized to stably cluster the patients into five different immune subtypes. Among them, IS1/2 was cold tumor with low tumor mutation burden (TMB), immunogenic cell death (ICDs), and immune checkpoints (ICPs), and IS4/5 was hot tumor with high TMB, ICDs, and ICPs. Monocle3 package was used to evaluate the immune status similarity and evolution in glioma, which identified cluster IS2A/2B within IS2 subtype to be more suitable vaccination receivers. Weighted gene co-expression network analysis identified five hub immune genes as the biomarkers of patients' immune status in glioma. In conclusion, NAT1, FRRS1, GTF2H2C, BRCA2, GRAP, NR5A2, ABCB4, ZNF90, ERCC6L, and ZNF813 are potential antigens suitable for glioma mRNA vaccine. IS1/2A/2B are suitable for mRNA vaccination.


Anti-migraine activity of freeze-dried latex obtained from Calotropis gigantea Linn.
Migraine which is characterized by a pulsating headache affected an estimated population of 12% worldwide. Herbal products like latex derived from Calotropis gigantea R. Br. (Asclepiadaceae) are a representative intervention to treat migraine traditionally. However, post-harvesting stability issues of latex affect its biological potential. Freeze-drying has been successfully employed for the encapsulation of herbal bioactive compounds resulting in stable dried preparations. Latex derived from Calotropis gigantea (C. gigantea) was microencapsulated using chitosan by freeze-drying (FDCG) method and compared with sun ray-dried latex (ADCG). Current investigation was aimed to improve the shelf life of latex by freeze-drying microencapsulation technique and evaluation of its anti-migraine potential. Dried latex powders (ADCG and FDCG) were evaluated in terms of phenolic content, coloring strength, first-order kinetic, color parameters (L*, a*, b*, C*, and E*), moisture, water activity, solubility, and hygroscopicity. Additionally, apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity were used to evaluate the anti-migraine potential of powdered latex. FDCG showed good physicochemical properties due to its higher concentration of phenolic and flavonoid contents. Moreover, FDCG significantly reduced the apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity in a dose-dependent manner through an interaction of dopaminergic and serotonergic receptors. In conclusion, the method developed for shelf life improvement of latex offered maximum protection over a period of 10 weeks with retaining its natural biological potential; thus, it can be effectively utilized in the treatment or management of migraine. Anti-migraine effect of Calotropis gigantea freeze-dried latex by inhibition of dopamine and serotonin receptors (D1 and D2: dopamine receptors; 5-HT: serotonin receptors); yellow color represents serotonergic, and blue color indicates dopaminergic neurons.


From binary to ternary solvent: morphology fine-tuning of D/A blends in PDPP3T-based polymer solar cells.
For the PDPP3T/PCBM system investigated here, atomic force microscopy, resonant soft X-ray scattering, and grazing incidence wide angle X-ray scattering are used as an initial set of tools to determine the surface texture, the bulk compositional morphology, and the crystallization behavior, respectively. We find systematic variations and relate them to device performance. A solvent mixture of DCB/CF/DIO = 76:19:5 (v/v/v) yields a PCE of 6.71%.


Improved Automatic Detection of New T2 Lesions in Multiple Sclerosis Using Deformation Fields.
Detection of disease activity, defined as new/enlarging T2 lesions on brain MR imaging, has been proposed as a biomarker in MS. However, detection of new/enlarging T2 lesions can be hindered by several factors that can be overcome with image subtraction. The purpose of this study was to improve automated detection of new T2 lesions and reduce user interaction to eliminate inter- and intraobserver variability. Multiparametric brain MR imaging was performed at 2 time points in 36 patients with new T2 lesions. Images were registered by using an affine transformation and the Demons algorithm to obtain a deformation field. After affine registration, images were subtracted and a threshold was applied to obtain a lesion mask, which was then refined by using the deformation field, intensity, and local information. This pipeline was compared with only applying a threshold, and with a state-of-the-art approach relying only on image intensities. To assess improvements, we compared the results of the different pipelines with the expert visual detection. The multichannel pipeline based on the deformation field obtained a detection Dice similarity coefficient close to 0.70, with a false-positive detection of 17.8% and a true-positive detection of 70.9%. A statistically significant correlation (r = 0.81, P value = 2.2688e-09) was found between visual detection and automated detection by using our approach. The deformation field-based approach proposed in this study for detecting new/enlarging T2 lesions resulted in significantly fewer false-positives while maintaining most true-positives and showed a good correlation with visual detection annotations. This approach could reduce user interaction and inter- and intraobserver variability.


[Smoking in pregnancy].
The course of pregnancy and delivery and the foetal outcome of women who smoked during pregnancy (n = 1751) were compared with nonsmokers (= 4937). The following variables were studied in retrospect: Duration of pregnancy, maternal weight gain, mode of delivery, foetal birthweight and the maturity of the newborn, Apgar scores, pH of the umbilical artery, perinatal mortality, frequency of foetal malformations, amount of amniotic fluid and the incidence of meconium staining, placental weight and the occurrence of placental infarctions. Birth weight, foetal length and head circumference were significantly smaller in the group of women who smoked. The incidence of babies with low birth weight and clinical signs of prematurity as well as placental infarctions was significantly increased in the same group. Gestational age was not different in smoking and nonsmoking gravidae. No statistical difference was found in the rate of C-sections, in Apgar scores, umbilical arterial pH, the incidence of malformations, perinatal mortality, and placental weight. Social factors were not considered in this study.


Parents' satisfaction with child psychiatry.
Effective social and healthcare services are important for recipient point of view. Reforms in field of social and health care affect straight to the lives of children, adolescents and families. Voice of the parents' of the child psychiatric patient must be heard during reforms. The purpose of this study was to explore the parents' satisfaction with the child psychiatric clinic in southern Finland in the autumn 2017. The questionnaire for parents' included 12 questions related to a single visit experience in clinic. In total, 168 responses were collected at the end of the visits. Likert scale responses were analysed statistically with nonparametric methods for the relationship between variables such as the respondent relationship to the child and the type of visit. The open-ended questions were analysed by qualitative content analysis. The relationship with the child was multifaceted: 54% were mothers and 18% fathers, 13% other adults and 3% child welfare workers. The respondents' age distribution was 18-62 years, and the average age was 39 years. The respondents were satisfied with their visit at the clinic. The respondents' relationship with the child was determined how successful the visit was in the point of view of respondent in some cases. There was no difference in the experience for the first-time visitors and returning visitors or the parents' who had visited the clinic at the same time. Even there was significant difference experiencing the visit in some cases, the respondents were satisfied and visits deemed to have benefit. The speed and availability of care and the skills and competence of the staff were appreciated. Atmosphere in the clinic was warm and positive. Development point of view, lack of information about the duration of the visit was raised to parents at the beginning of the visit.


A patient-level calibration framework for evaluating surveillance strategies: a case study of mammographic follow-up after early breast cancer.
Currently all women who have completed their primary treatment for early breast cancer are invited to receive routine annual mammography. There is no randomized controlled trial evidence to support this schedule, and model-based analysis is required. This paper describes a novel data collection and model calibration process to analyze the cost-effectiveness of alternative follow-up schedules for early breast cancer survivors. A discrete event simulation model describes the progression of early breast cancer after the completion of primary treatment, representing impalpable and palpable recurrence and the detection of impalpable disease via follow-up mammography. Retrospective data from the South Australian Cancer Registry and clinical and administrative hospital databases were linked for 407 postmenopausal women diagnosed with moderate-prognosis early breast cancer from 2000 to 2008. These data formed the basis of a patient-level probabilistic calibration process. For 50- to 69-year-old survivors, annual follow-up for 5 years, with visits every 2 years thereafter, appears to be cost-effective. For women aged 70 to 79 years at diagnosis, a surveillance schedule similar to general population screening (2 yearly) appears to be most cost-effective if high rates of adherence can be maintained. This study demonstrated the potential value of combining linked, retrospective data and decision analytic modeling to provide estimates of costs and health outcomes that are sufficiently robust to inform cancer clinical guidelines and individual patient decisions regarding appropriate follow-up schedules.


Systemic Challenges in Internship Training for Health-Service Psychology: A Call to Action From Trainee Stakeholders.
The challenges observed in health service psychology (HSP) training during COVID-19 revealed systemic and philosophical issues that preexisted the pandemic, but became more visible during the global health crisis. In a position paper written by 23 trainees across different sites and training specializations, the authors use lessons learned from COVID-19 as a touchstone for a call to action in HSP training. Historically, trainee voices have been conspicuously absent from literature about clinical training. We describe longstanding dilemmas in HSP training that were exacerbated by the pandemic and will continue to require resolution after the pandemic has subsided. The authors make recommendations for systems-level changes that would advance equity and sustainability in HSP training. This article advances the conversation about HSP training by including the perspective of trainees as essential stakeholders.


Intracranial evaluation of the epileptogenic zone in regional infrasylvian polymicrogyria.
To define the relationship between the epileptogenic zone and the polymicrogyric area using intracranial electroencephalography (EEG) recordings in patients with structural epilepsy associated with regional infrasylvian polymicrogyria (PMG). We retrospectively reviewed the medical charts, scalp, and intracranial video-EEG recordings, neuroimaging findings, and neuropsychological evaluations of four patients with refractory temporal lobe epilepsy related to PMG who consequently underwent resective surgery. High-resolution magnetic resonance imaging (MRI) revealed temporal lobe PMG in all cases, accompanied by hippocampal malrotation and closed lip schizencephaly in 3/4 cases, respectively. In intracranial recordings, interictal spike activity was localized within the PMG in only 2/4 and within the amygdala, hippocampus, and entorhinal cortex in all cases. In the first patient, two epileptogenic networks coexisted: the prevailing network initially involved the mesial temporal structures with spread to the anterior PMG; the secondary network successively involved the anterior part of the PMG and later the mesial temporal structures. In the second patient, the epileptogenic network was limited to the mesial temporal structures, fully sparing the PMG. In the third patient, the epileptogenic network first involved the mesial temporal structures and later the PMG. Conversely, in the last case, part of the PMG harbored an epileptogenic network that propagated to the mesial temporal structures. Consistent with these findings a favorable outcome (Engel class I in three of four patients; Engel class II in one of four) at last follow-up was obtained by a resection involving parts of the PMG cortex in three of four and anteromesial temporal lobe structures in another three of four cases. Infrasylvian PMG displays a heterogeneous epileptogenicity and is occasionally and partially involved in the epileptogenic zone that commonly includes the mesial temporal structures. Our results highlight the intricate interrelations between the MRI-detectable lesion and the epileptogenic zone as delineated by intracranial recordings. Seizure freedom can be accomplished as a result of a meticulous intracranial study guiding a tailored resection that may spare part of the PMG.


Dermomyotomal origin of the ribs as revealed by extirpation and transplantation experiments in chick and quail embryos.
To elucidate role of the dermomyotome in the formation of the axial skeleton, we performed extirpation and transplantation experiments on the dermomyotomes in chick and quail embryos. When the thoracic dermomyotomes of chick embryos were removed, the intercostal muscles and the distal ribs were deficient, while the proximal ribs were more or less normal. Quail tissues including the dermomyotome, the ectoderm and the medial edge of lateral plate, were transplanted to replace chick dermomyotomes. In these chimeras, the ribs, which would be deficient without the back-transplantation, were recovered. The cells of the recovered part of the ribs as well as the intercostal muscles were derived from the quail transplants. These findings suggest that the distal rib originated from the dermomyotomes and not the sclerotome as previously believed. To localize the origin of the distal rib further, we removed restricted regions of the dermomyotomes along the mediolateral and the rostrocaudal axis. The more lateral the part of the dermomyotomes that we removed, the more distal the part of the ribs affected. On the contrary, when the rostral and caudal edges of the dermomyotomes were removed, only the vertebral ribs showed extensive deficiencies while removal of the middle part between the edges caused less deficiency. The sternal ribs were not deficient in either case, but were extensively affected when the entire lateral edge of dermomyotomes was included in the region removed. We conclude that the lateral edges of the dermomyotomes are the primordia of the sternal ribs, and the rostral and/or caudal edges of the medial part of dermomyotomes are the primordia of the distal part and not of the proximal part of the vertebral ribs.


Intraindividual analysis of instantaneous heart rate variability.
We examined the use and potential of quantifying instantaneous heart rate variability (HRV) using a joint time-frequency and time-domain methods. These new techniques are promising, because they provide tools to quantify nonstationary, beat-by-beat changes in HRV components, and are therefore flexible with respect to the design of experimental protocols. A smoothed pseudo-Wigner-Ville distribution (SPWVD) and a time-domain index using polynomial filtering produced fairly coherent estimates of band-specific HRV amplitudes, whereas SPWVD yielded additional information on the frequency characteristics of HRV. Instantaneous HRV appeared to have a complex and a frequency-specific relationship to cardiac activity and electrodermal activity, It is concluded that the time-frequency analysis of HRV is a very promising method for mapping transient changes in the frequency and amplitude characteristics of cardiac dynamics.


Comparison of Communication Channels for Large-Scale Type 2 Diabetes Risk Screening and Intervention Recruitment: Empirical Study.
Clinical trials have shown that type 2 diabetes (T2D) is preventable through lifestyle interventions targeting high-risk people. Nevertheless, large-scale implementation of risk identification followed by preventive interventions has proven to be challenging. Specifically, recruitment of participants into preventive interventions is an important but often overlooked part of the intervention. This study aims to compare the reach and yield of different communication channels to engage people at increased risk of T2D to fill in a digital screening questionnaire, with emphasis on reaching those at most risk. The participants expressing their willingness to participate is the final step in the risk screening test, and we aim to determine which channels had the most participants reach this step. We established a stepwise web-based T2D risk screening tool with automated feedback according to the T2D risk level and, for those who were eligible, an invitation to participate in the StopDia prevention intervention study conducted in a primary health care setting. The risk estimate was based on the Finnish Diabetes Risk Score; history of repeatedly measured high blood glucose concentration; or, among women, previous gestational diabetes. We used several channels to invite people to the StopDia web-based screening tool, and respondents were classified into 11 categories based on the channel through which they reported having learned about StopDia. The demographics of respondents reached via different communication channels were compared using variance analysis. Logistic regression was used to study the respondents' likelihood of progressing through risk screening steps. A total of 33,399 persons started filling the StopDia screening tool. Of these, 86.13% (28,768/33,399) completed the test and named at least one communication channel as the source of information about StopDia. Altogether, 26,167 persons filled in sufficient information to obtain risk estimates. Of them, 53.22% (13,925/26,167) were at increased risk, 30.06% (7866/26,167) were men, and 39.77% (10,136/25,485) had low or middle education levels. Most frequently mentioned channels were workplace (n=6817), social media or the internet (n=6712), and newspapers (n=4784). The proportion of individuals at increased risk was highest among those reached via community pharmacies (415/608, 68.3%) and health care (1631/2535, 64.33%). The communication channel reaching the largest percentage of interested and eligible men (1353/3979, 34%) was relatives or friends. Health care (578/1069, 54.07%) and radio or television (225/487, 46.2%) accounted for the largest proportion of people with lower education. Communication channels reaching a large number of people, such as social media and newspapers, were the most effective channels for identifying at-risk people. Personalized approaches increased the engagement of men and less-educated people. Community pharmacies and health care services reached people with a particularly high T2D risk. Thus, communication and recruitment channels should be selected and modified based on the intended target group. RR2-10.1186/s12889-019-6574-y.


Induction of Apoptotic Cell Death by Oral Streptococci in Human Periodontal Ligament Cells.
Initiation and progression of oral infectious diseases are associated with streptococcal species. Bacterial infection induces inflammatory responses together with reactive oxygen species (ROS), often causing cell death and tissue damage in the host. In the present study, we investigated the effects of oral streptococci on cytotoxicity and ROS production in human periodontal ligament (PDL) cells. Streptococcus gordonii showed cell cytotoxicity in a dose- and time-dependent manner. The cytotoxicity might be due to apoptosis since S. gordonii increased annexin V-positive cells, and the cytotoxicity was reduced by an apoptosis inhibitor, Z-VAD-FMK. Other oral streptococci such as Streptococcus mitis, Streptococcus sanguinis, and Streptococcus sobrinus also induced apoptosis, whereas Streptococcus mutans did not. All streptococci tested except S. mutans triggered ROS production in human PDL cells. Interestingly, however, streptococci-induced apoptosis appears to be ROS-independent, as the cell death induced by S. gordonii was not recovered by the ROS inhibitor, resveratrol or n-acetylcysteine. Instead, hydrogen peroxide (H2O2) appears to be important for the cytotoxic effects of streptococci since most oral streptococci except S. mutans generated H2O2, and the cytotoxicity was dramatically reduced by catalase. Furthermore, streptococcal lipoproteins are involved in cytotoxicity, as we observed that cytotoxicity induced by the lipoprotein-deficient S. gordonii mutant was less potent than that by the wild-type and was attenuated by anti-TLR2-neutralizing antibody. Indeed, lipoproteins purified from S. gordonii alone were sufficient to induce cytotoxicity. Notably, S. gordonii lipoproteins did not induce H2O2 or ROS but cooperatively induced cell death when co-treated with H2O2. Taken together, these results suggest that most oral streptococci except S. mutans efficiently induce damage to human PDL cells by inducing apoptotic cell death with bacterial H2O2 and lipoproteins, which might contribute to the progression of oral infectious diseases such as apical periodontitis.


[Attitude to control, its foundations and autobiographical memories].
Ten social tasks were described orally to 61 subjects aged 17 to 20. The subjects had to decide whether or not they thought they would be able to complete the tasks. They were also asked about their response certainty and their familiarity with the situation. In addition, the latency time between the end of the description of the problem and the beginning of the utterance of the control belief was measured. We were mainly interested in finding out what arguments (reference to episodes, to dispositional attributes, to the participant's control share, and to rules) the subjects would preferably use to justify their belief or non-belief in control. In addition, we measured general control belief as further independent variable. The results showed that references to dispositional attributes were the most frequently used arguments, followed by references to episodes, to the participant's control share, and to rules. However, the response certainty was highest in cases when a concrete personal experience was mentioned. Response latencies were also shortest when the control belief utterance was justified by invoking a concrete personal experience, followed by dispositional attributes, participant information, and rules, in this order. Apparently, the subjects preferred episodic justifications of their control belief. The subjects felt more certain about their statement when they claimed to have control over a given situation than when they thought they did not have control. General control belief had no influence on the preference for particular arguments or on the latency times.


Prospects for stem cell transplantation in the treatment of hepatic disease.
Stem cell therapy has the potential to provide a valuable adjunct to the management of hepatic disease. Preclinical studies have demonstrated a range of endogenous repair processes that can be exploited through stem cell therapy. Initial translational studies have been encouraging and have suggested improved liver function in advanced chronic liver disease and enhanced liver regeneration after portal vein embolization. This article reviews the potential for stem cell therapies to enhance hepatic regeneration in acute and chronic hepatic disease and is based on a MEDLINE and PubMed search for English language articles investigating mechanisms of hepatic regeneration and delivery of cell therapies. Two main mechanisms of potential stem cell therapy delivery have emerged: (1) a direct contribution to the functional hepatocyte population with embryonic, induced pluripotent, or adult stem cells and (2) the promotion of endogenous regenerative processes with bone marrow-derived stem cells. Bioartificial hepatic support systems may be proven to be an effective method of using ex vivo differentiated hepatocytes and be indicated as a bridging therapy to definitive surgery in acute liver failure. The administration of bone marrow-derived stem cells may enhance liver regeneration in chronic liver disease after portal vein embolization and could facilitate regeneration after partial hepatic resection. Ultimately, the most appropriate hepatic disease targets for stem cell therapies will become apparent as mechanisms of stem involvement in hepatic regeneration are further elucidated.


Concomitant Cutaneous Langerhans Cell Hystiocytosis and Leukemia Cutis.
Leukemia cutis develops in <4% of all acute leukemias. Concurrent acute myeloid leukemia (AML) and Langerhans cell histiocytosis (LCH) is rare, with most cases involving lymph nodes or spleen, and no cutaneous involvement. We report the case of a 59-year-old man who presented with fever, malaise, and fatigue. The CBC showed leukocytosis (30.4 × 10/L, 9% blasts), anemia, and thrombocytopenia. Bone marrow biopsy was diagnosed with AML, not otherwise specified, with mutations of FLT3 and IDH2 (R140Q). The patient developed skin rash on the right flank with the clinical differential diagnosis of herpes simplex virus or varicella-zoster virus infection/reactivation versus leukemia cutis. A skin biopsy showed leukemia cutis in mid and deep dermis. Immunohistochemistry positive for CD4, CD33, CD117, and myeloperoxidase (MPO) supported myeloid and monocytic differentiation. Clusters of Langerhans cells positive for S100, CD1a, CD4, langerin and aberrant CD33 and MPO were found admixed with the AML cells. Langerhans cells were negative for BRAF V600E by immunohistochemistry. The diagnosis of leukemia cutis and concomitant LCH was established. The aberrant expression of CD33 and MPO shared by AML and LCH suggests a possible relationship among these 2 lesions. No LCH or Langerhans cell differentiation was found in the bone marrow. The patient achieved complete remission 4 months after chemotherapy and the skin lesions resolved. To our knowledge, we present for the first time a case of concomitant cutaneous LCH and leukemia cutis.


[Biologic effects of hyperthermia and radiation on gastric cancer cells (SGC-7901) in vitro--I. Influence on cell growth curve, number of colonies and mitosis].
Biologic effects of hyperthermia (42 degrees-44 degrees C) and radiation on SGC-7901 were studied quantitatively and morphologically. Action of hyperthermia and radiation on the population and subpopulation of cells was monitored by cell growth curve and colony counts. The results show that both hyperthermia (43 degrees C for 30 min) and radiation (500 rad) can cause the cell kill and growth curve decrease but the cells still tend to proliferate. The synergistic action of heat plus radiation is demonstrated when they are given in the interval of 30 min. The thermal enhance rate was 1.27 and 1.37 for survival rate down to 2% and 5%. The concentration of potassium ions in the media is increased with cell kill after heat and radiation. The damage from heating appears like a direct kill or immediate death, the damage from radiation reveals delayed or metabolic death. Partial and transitory redistribution of cell cycle occurs following heating or radiation. Delayed division is more marked following heating than radiation. The synchronization effect may be used to hit the cycling tumor cells in the most radiosensitive phase.


Emotionally focused couple therapy in cancer survivor couples with marital and sexual problems: a replicated single-case experimental design.
The current research examined the effect of Emotionally Focused Couples Therapy (EFCT) on perceived intimacy, affect, and dyadic connection in cancer survivor couples with relationship challenges. In this longitudinal replicated single-case study, positive and negative affect, intimacy, partner responsiveness, and expression of attachment-based emotional needs were reported every 3 days before and during treatment. Thirteen couples, with one partner having survived colorectal cancer or breast cancer, participated for the full duration of the study. Statistical analysis of the data was performed using randomization tests, piecewise regression, and multilevel analyses. Adherence to the therapeutic protocol was tested and found adequate. Compared with baseline, significant positive effects on affect variables were found during the therapeutic process. Positive affect increased and negative affect decreased. Partner responsiveness, perceived intimacy, and the expression of attachment-based emotional needs improved, but only in the later phase of treatment. Results at the group level were statistically significant, whereas effects at the individual level were not. This study found positive group-level effects of EFCT on affect and dyadic outcome measures in cancer survivors. The positive results warrant further research, including randomized clinical trials, to replicate these effects of EFCT in cancer survivor couples experiencing marital and sexual problems.


Precision oncology: origins, optimism, and potential.
Imatinib, the first and arguably the best targeted therapy, became the springboard for developing drugs aimed at molecular targets deemed crucial to tumours. As this development unfolded, a revolution in the speed and cost of genetic sequencing occurred. The result--an armamentarium of drugs and an array of molecular targets--set the stage for precision oncology, a hypothesis that cancer treatment could be markedly improved if therapies were guided by a tumour's genomic alterations. Drawing lessons from the biological basis of cancer and recent empirical investigations, we take a more measured view of precision oncology's promise. Ultimately, the promise is not our concern, but the threshold at which we declare success. We review reports of precision oncology alongside those of precision diagnostics and novel radiotherapy approaches. Although confirmatory evidence is scarce, these interventions have been widely endorsed. We conclude that the current path will probably not be successful or, at a minimum, will have to undergo substantive adjustments before it can be successful. For the sake of patients with cancer, we hope one form of precision oncology will deliver on its promise. However, until confirmatory studies are completed, precision oncology remains unproven, and as such, a hypothesis in need of rigorous testing.


Causal Inference in the Perception of Verticality.
The perceptual upright is thought to be constructed by the central nervous system (CNS) as a vector sum; by combining estimates on the upright provided by the visual system and the body's inertial sensors with prior knowledge that upright is usually above the head. Recent findings furthermore show that the weighting of the respective sensory signals is proportional to their reliability, consistent with a Bayesian interpretation of a vector sum (Forced Fusion, FF). However, violations of FF have also been reported, suggesting that the CNS may rely on a single sensory system (Cue Capture, CC), or choose to process sensory signals based on inferred signal causality (Causal Inference, CI). We developed a novel alternative-reality system to manipulate visual and physical tilt independently. We tasked participants (n = 36) to indicate the perceived upright for various (in-)congruent combinations of visual-inertial stimuli, and compared models based on their agreement with the data. The results favor the CI model over FF, although this effect became unambiguous only for large discrepancies (±60°). We conclude that the notion of a vector sum does not provide a comprehensive explanation of the perception of the upright, and that CI offers a better alternative.


Using population attributable risk to help target preventive interventions for adolescent depression.
Prevention of adolescent depression has become a public health priority in the United States (US) and in other developed economies. Population attributable risk (PAR) can provide an estimate of the incidence reduction that would occur if a particular factor were removed. To determine PAR of vulnerability factors for new-onset depressive episodes in United States (US) adolescents. National Longitudinal Study of Adolescent Health. The sample was comprised of nationally representative adolescents in grades 7-12, with mean age of 15.7 years. We determined PAR for identified vulnerability factors for US adolescents measured at baseline predicting a depressive episode at one-year follow-up. The baseline factors included socio-demographics and physical health factors; interpersonal relations; community and school factors and cognition/affect regulation. Factors with significant PAR were identified from each major domain of adolescent life. With the exception of age, sexual activity had the highest PAR. Interpersonal relations, particularly those involving family members rather than peers, represented the most important group of contributing factors. Similarly, low levels of constructive community involvement (e.g. religious activity) and higher levels of delinquent activity had significant PAR. Current depressed mood had relatively high PAR whereas negative self-cognitions had relatively low PAR. Poor affect regulation, existent depressed mood, and accompanying negative cognitions are important potential intervention targets. Our findings also suggest expanding the focus of preventive interventions to encompass all interpersonal and community domains of the adolescent experience.


Prognostic factors in severely head injured adult patients with epidural haematoma's.
A medline search back to 1975 was undertaken to identify relevant papers published on epidural haematomas. The search was restricted, whenever possible, to adult age and to comatose patients. Forty four relevant reports were identified. Only 4 papers reported results on multivariate analysis. In terms of prognosis, the following parameters were found to be significant: age, time from injury to treatment, immediate coma or lucid interval, presence of pupillary abnormalities, GCS/motor score on admission. CT findings (haematoma volume, degree of midline shift, presence of signs of active haematoma bleeding, associated intradural lesion) and post-operative ICP. To compare different casistics we need more informations about patients's outcome in the referral area of the neurosurgical centers, about the number of direct admissions and about the number of patients showing clinical deterioration.


Cycloheximide blocks nicotinamide action on phosphate excretion in thyroparathyroidectomized rats.
Nicotinamide causes marked inhibition of phosphate (Pi) reabsorption in the renal proximal tubule and this can be detected both as a specific decrease in Na+-dependent Pi uptake by isolated brush border membrane (BBM) vesicles and as a marked increase in urinary Pi excretion. In the present study, thyroparathyroidectomized (TPTX) rats were adapted to low-Pi diet and injected with cycloheximide (CHX), an inhibitor of protein synthesis, prior to nicotinamide treatment. Compared to rats that received nicotinamide alone, the pretreatment with CHX did not alter the inhibitory action of nicotinamide on BBM uptake of Pi. However, CHX completely blocked the phosphaturic response. We conclude that, at least in TPTX rats adapted to low-Pi diet, nicotinamide inhibits Pi reabsorption not only in the proximal convoluted tubule but also in other nephron segments such as the pars recta or distal sites. Nicotinamide action on these additional sites is dependent on protein synthesis, in contrast to its action in the proximal convoluted tubule.


A Very Rare Partial Trisomy Syndrome: De Novo Duplication of 16q12.1q23.3 in a Turkish Girl with Developmental Delay and Facial Dysmorphic Features.
Trisomy 16 is the most common type of autosomal trisomy associated with spontaneous abortion and is incompatible with life. Upon examining previously reported cases of partial chromosome 16q duplication, it was noted that the majority of cases had complex chromosomal abnormalities due to parental balanced chromosomal translocation carriage. The clinical presentation of very rare pure partial trisomy 16q cases was associated with congenital anomalies, facial dysmorphic findings and intellectual disability. In this study, we evaluated the physical characteristics and genetic data of an 8-month-old girl with developmental delay and facial dysmorphic features. Dysmorphic features including prominent metopic suture, synophrys, asymmetric head shape, triangular and asymmetric face, telecanthus, epicanthal folds, down-slanting palpebral fissures, microphthalmia of the left eye, anteverted nares, smooth and tented philtrum, microretrognathia, low-set posteriorly rotated ears, auricular pits, high-arched palate, thin upper lip and hypotonia were recorded. Her karyotype was 46,XX,add(16)(q24). To identify the extension of the duplicated section, array comparative genomic hybridization (aCGH) analysis was performed, which showed a de novo 29.8 Mb duplication [arr[hgl9] 16q12.1q23.3(52459169-82285105) x 3], interpreted to be pathogenic. We present this case report to clarify the clinical findings of a rare chromosomal anomaly, discuss the genes that may be related to the phenotype and advance the literature in terms of knowledge regarding genotypephenotype correlation.


Direct stimulation of Vav guanine nucleotide exchange activity for Ras by phorbol esters and diglycerides.
We recently identified Vav as a Ras-activating guanine nucleotide exchange factor (GEF) stimulated by a T-cell antigen receptor-coupled protein tyrosine kinase (PTK). Here, we describe a novel, protein kinase-independent alternative pathway of Vav activation. Phorbol ester, 1,2-diacylglycerol, or ceramide treatment of intact T cells, Vav immunoprecipitates, or partially purified Vav generated by in vitro translation or COS-1 cell transfection stimulated the Ras exchange activity of Vav in the absence of detectable tyrosine phosphorylation. GEF activity of gel-purified Vav was similarly stimulated by phorbol myristate acetate (PMA). Stimulation was resistant to PTK and protein kinase C inhibitors but was blocked by calphostin, a PMA and diacylglycerol antagonist. In vitro-translated Vav lacking its cysteine-rich domain, or mutated at a single cysteine residue within this domain (C528A), was not stimulated by PMA but was fully activated by p56lck. This correlated with increased binding of radiolabeled phorbol ester to COS-1 cells expressing wild-type, but not C528A-mutated, Vav. Thus, Vav itself is a PMA-binding and -activated Ras GEF. Recombinant interleukin-1 alpha stimulated Vav via this pathway, suggesting that diglyceride-mediated Vav activation may couple PTK-independent receptors which stimulate production of lipid second messengers to Ras in hematopoietic cells.


Characterizing electronic and atomic structures for amorphous and molecular metal oxide catalysts at functional interfaces by combining soft X-ray spectroscopy and high-energy X-ray scattering.
Amorphous thin film materials and heterogenized molecular catalysts supported on electrode and other functional interfaces are widely investigated as promising catalyst formats for applications in solar and electrochemical fuels catalysis. However the amorphous character of these catalysts and the complexity of the interfacial architectures that merge charge transport properties of electrode and semiconductor supports with discrete sites for multi-step catalysis poses challenges for probing mechanisms that activate and tune sites for catalysis. This minireview discusses advances in soft X-ray spectroscopy and high-energy X-ray scattering that provide opportunities to resolve interfacial electronic and atomic structures, respectively, that are linked to catalysis. This review discusses how these techniques can be partnered with advances in nanostructured interface synthesis for combined soft X-ray spectroscopy and high-energy X-ray scattering analyses of thin film and heterogenized molecular catalysts. These combined approaches enable opportunities for the characterization of both electronic and atomic structures underlying fundamental catalytic function, and that can be applied under conditions relevant to device applications.


Estimation of the case fatality rate based on stratification for the COVID-19 outbreak.
This work is motivated by the recent worldwide pandemic of the novel coronavirus disease (COVID-19). When an epidemiological disease is prevalent, estimating the case fatality rate, the proportion of deaths out of the total cases, accurately and quickly is important as the case fatality rate is one of the crucial indicators of the risk of a disease. In this work, we propose an alternative estimator of the case fatality rate that provides more accurate estimate during an outbreak by reducing the downward bias (underestimation) of the naive CFR, the proportion of deaths out of confirmed cases at each time point, which is the most commonly used estimator due to the simplicity. The proposed estimator is designed to achieve the availability of real-time update by using the commonly reported quantities, the numbers of confirmed, cured, deceased cases, in the computation. To enhance the accuracy, the proposed estimator adapts a stratification, which allows the estimator to use information from heterogeneous strata separately. By the COVID-19 cases of China, South Korea and the United States, we numerically show the proposed stratification-based estimator plays a role of providing an early warning about the severity of a epidemiological disease that estimates the final case fatality rate accurately and shows faster convergence to the final case fatality rate.


Economic evaluation of a complex intervention (Engager) for prisoners with common mental health problems, near to and after release: a cost-utility and cost-consequences analysis.
People in prison experience a range of physical and mental health problems. Evaluating the effectiveness and efficiency of prison-based interventions presents a number of methodological challenges. We present a case study of an economic evaluation of a prison-based intervention ("Engager") to address common mental health problems. Two hundred and eighty people were recruited from prisons in England and randomised to Engager plus usual care or usual care. Participants were followed up for 12 months following release from prison. The primary analysis is the cost per quality-adjusted life year (QALY) gained of Engager compared to usual care from a National Health Service (NHS) perspective with QALYs calculated using the CORE 6 Dimension. A cost-consequences analysis evaluated cross-sectoral costs and a range of outcomes. From an NHS perspective, Engager cost an additional £2737 per participant (95% of iterations between £1029 and £4718) with a mean QALY difference of - 0.014 (95% of iterations between - 0.045 and 0.017). For the cost-consequences, there was evidence of improved access to substance misuse services 12 months post-release (odds ratio 2.244, 95% confidence Interval 1.304-3.861). Engager provides a rare example of a cost-utility analysis conducted in prisons and the community using patient-completed measures. Although the results from this trial show no evidence that Engager is cost-effective, the results of the cost-consequences analysis suggest that follow-up beyond 12 months post-release using routine data may provide additional insights into the effectiveness of the intervention and the importance of including a wide range of costs and outcomes in prison-based economic evaluations. (ISRCTN11707331).


Acyclovir prophylaxis for pregnant women with a known history of herpes simplex virus: a cost-effectiveness analysis.
Previous literature has shown acyclovir to be cost-effective as prophylaxis for women with genital symptomatic herpes simplex virus infection recurrence during pregnancy. We extend this analysis by adding quality-adjusted life year measurements and considering women with a diagnosed history of herpes simplex virus infection but without recurrence in pregnancy. A decision analytic model was designed that compared acyclovir prophylaxis versus no acyclovir for women with a history of diagnosed genital herpes simplex virus infection but without recurrence in pregnancy. Sensitivity analysis and Monte Carlo simulations were performed to test for robustness. We found that 22,286 women must be treated to prevent 1 neonatal death, 8985 women to prevent 1 affected child, and 177 women to prevent 1 cesarean delivery. As compared with no acyclovir, acyclovir prophylaxis at 36 weeks of gestation saves approximately dollar 20 per person and increases total quality-adjusted life years by 0.01. In univariate sensitivity analysis, this result was robust to all reasonable probability and quality-adjusted life year estimates. Monte Carlo simulation demonstrated acyclovir to be cost-effective 100% of the time and cost saving >99% of the time. Acyclovir prophylaxis versus no treatment for pregnant women with a diagnosed history of genital herpes simplex virus infection but without recurrence during pregnancy is cost-effective over a wide range of assumptions.


A 96-kDa glycyrrhizin-binding protein (gp96) from soybeans acts as a substrate for casein kinase II, and is highly related to lipoxygenase 3.
A 96-kDa glycyrrhizin (GL)-binding protein (gp96) was purified to apparent homogeneity from an aqueous extract of soybeans by means of successive DEAE-cellulose column chromatography, gel filtration on Superdex 200pg, GL-affinity column chromatography, and ion-exchange chromatography on a Mono S column (HPLC). The protein was identified as a GL-binding protein since it specifically binds to [3H]GA. Moreover, it is a lipoxygenase (an enzyme that catalyzes the oxygenation of unsaturated fatty acids) since (i) it displays lipoxygenase (LOX) activity at pH 6.5; (ii) it is recognized on Western blot analysis by antibodies against LOX-1 and LOX-2; and (iii) the sequence of the N-terminal 21 amino acid residues (SNDVYLPRDEAFGHLKSSDFL) of a 42-kDa fragment (p42) proteolytically generated from gp96 is identical to a sequence of soybean LOX-3. In addition, GL, glycyrrhetinic acid (GA) and soyasaponin beta g slightly inhibited LOX activity of the purified gp96 fraction, whereas oGA (a GA derivative) greatly inhibited its activity. Furthermore, CK-II catalyzed phosphorylation of gp96 was stimulated significantly by GL at doses between 1 and 10 microM, but this phosphorylation was inhibited completely by 50 microM GL. All these results taken together suggest that (i) gp96 purified from soybeans as a GL-binding protein belongs to the LOX family; and (ii) triterpenoid saponins, including GL, are involved in the regulation of the activities of CK-II and LOXs in plants, such as soybeans and roots of liquorice, which contain large quantities of saponins.


Ischemia-reperfusion injury of the retina is linked to necroptosis via the ERK1/2-RIP3 pathway.
Ischemia-reperfusion (IR) injury is involved in the pathology of many retinal disorders since it contributes to the death of retinal neurons and the subsequent decline in vision. We determined the molecular patterns of some of the principal molecules involved in necroptosis and investigated whether IR retinal injury is associated with the extracellular signal-regulated kinase-1/2- receptor-interacting protein kinase 3 (ERK1/2-RIP3) pathway. The cellular and subcellular localization of molecules involved in the cell death pathway, including RAGE, ERK1/2, FLIP, and RIP3, was determined with immunohistochemistry of cryosections of IR-injured retina from 2-month-old Long Evans rats. The total and phosphorylated protein levels were analyzed with quantitative western blots. ERK1/2 activity was inhibited by intravitreal injection of U0126, a highly selective inhibitor of mitogen-activated protein kinase 1/2 (MEK1/2). The IR-injured rat retinas expressed two RAGE isoforms with different intracellular localizations at early time points after injury. At that time point, frame inhibition of ERK activation decreased RIP3 accumulation and cell death. FLIP was detected in the IR-injured rat retinas at early time points after ischemia reperfusion. We report that the necroptotic cell death mechanism is executed by an ERK1/2-RIP3 pathway in the retinal ganglion cells in early stages after IR injury. Inhibition of ERK1/2 activity increased retinal ganglion cell (RGC) survival indicating that targeting of this pathway within the initial 12 h after IR injury can be used to inhibit the necroptosis pathway. We also provide evidence that a novel RAGE isoform is expressed in the early stages in rat retinal RGCs.


Spider silk colour covaries with thermal properties but not protein structure.
Understanding how and why animal secretions vary in property has important biomimetic implications as desirable properties might covary. Spider major ampullate (MA) silk, for instance, is a secretion earmarked for biomimetic applications, but many of its properties vary among and between species across environments. Here, we tested the hypothesis that MA silk colour, protein structure and thermal properties covary when protein uptake is manipulated in the spider Trichonephila plumipes. We collected silk from adult female spiders maintained on a protein-fed or protein-deprived diet. Based on spectrophotometric quantifications, we classified half the silks as 'bee visible' and the other half 'bee invisible'. Wide angle X-ray diffraction and differential scanning calorimetry were then used to assess the silk's protein structure and thermal properties, respectively. We found that although protein structures and thermal properties varied across our treatments only the thermal properties covaried with colour. This ultimately suggests that protein structure alone is not responsible for MA silk thermal properties, nor does it affect silk colours. We speculate that similar ecological factors act on silk colour and thermal properties, which should be uncovered to inform biomimetic programmes.


Expression and processing of prohormones in nonendocrine cells.
Pancreatic polypeptide (PP) and gastrin are initially synthesized as larger precursors that require posttranslational processing to produce the biologically active peptides. These steps include tryptic cleavage at paired basic residues, their subsequent removal by carboxypeptidase H, and formation of a carboxy-terminal amide moiety via the action of peptidyl-glycine alpha-amidating monooxygenase (PAM). Although these posttranslational processing reactions are presumed to occur primarily in the secretory granule of endocrine cells, nonendocrine cells that do not possess these structures nevertheless are able to posttranslationally process a wide variety of proteins destined for export. In these studies we sought to determine whether the mechanisms for prohormone processing are present in nonendocrine cell lines. We examined two fibroblast cell lines (psi-2, BHK) a hepatocyte cell line (Hepa), and an exocrine pancreatic cell line (AR42J). We used the pZIPneo(SVX) retroviral vector to express cDNA clones encoding human PP and gastrin in the nonendocrine cells. Transfected psi-2, BHK, and Hepa cells produced a precursor of PP that appeared to be secreted constitutively, with little remaining in intracellular stores. Almost no posttranslational processing of the PP precursor was evident in these cells. By contrast, AR42J cells were capable of expressing and storing fully processed and carboxy-terminally amidated PP and gastrin. These data support the notion that the sorting mechanisms in endocrine and exocrine cells are similar and that the posttranslational processing of peptide hormone precursors requires storage in secretory granules.(ABSTRACT TRUNCATED AT 250 WORDS)


Outcome reporting discrepancies between trial entries and published final reports of orthodontic randomized controlled trials.
The aim of this study was to identify outcome-related discrepancies between registry trial entries and final published reports in orthodontic randomized controlled trials (RCTs). The percentage of registered orthodontic RCTs was also recorded. Five trial registries, ClinicalTrials.gov (https://clinicaltrials.gov/), International Standard Randomised Controlled Trial Number registry (http://www.isrctn.com/), European Union Clinical Trials Register (https://www.clinicaltrialsregister.eu/), Australia New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) and Clinical Trials Registry of India (www.ctri.nic.in/) were searched up to April 2018 in order to identify completed orthodontic RCTs. The unique trial identifier, the title and authors name were used to search for publications based on entries within Google (https://www.google.com), Google Scholar (https://scholar.google.gr/) and MEDLINE via PubMed (https://www.ncbi.nlm.nih.gov/pubmed/). Outcome reporting discrepancies and a number of other entry/publication characteristics were recorded including timing of registration, type of journal/publication, significance of the primary outcome in the final report. The number of trials registered among the total number of published RCTs in orthodontics was recorded within the time span assessed. One hundred and twenty-four entries were identified for completed orthodontic RCTs, whereas 53 of those were related to published final reports. Outcome reporting discrepancies were ascertained for 47 per cent of publications (n = 2 5); discrepancies were more prevalent for non-primary outcomes (n = 21, 40 per cent). Only 16 per cent of the published orthodontic RCTs had been registered. Only a subset of trial entries were assessed as these were related to publication records. Registration of clinical trials in orthodontics remains far from universal. A significant level of outcome reporting discrepancy was observed within this subset of registered trials.


Evaluation of the lubricating effect of magnesium stearate and glyceryl behenate solid lipid nanoparticles in a direct compression process.
The aim of this study was to develop solid lipid nanoparticles (SLN) and introduce them into a direct compression process to evaluate their lubricant properties. The study consisted of preparing glyceryl behenate SLN (Compritol® 888 ATO) by hot dispersion, and magnesium stearate SLN by a novel nanoprecipitation/ion exchange method. The ejection force was measured for nanosystems and raw materials in a formulation typically used for direct compression. The smallest particle sizes obtained were 456 nm for Compritol® 888 ATO and 330 nm for magnesium stearate. Results show that the NPs used as lubricants in a direct compression model formulation provided efficient lubrication by maintaining the lubricating properties of the system, thereby decreasing the amount of lubricant used compared to the raw material. The lubricating effect showed an increase of 15-30% for magnesium stearate and Compritol® 888 ATO, compared to the raw material at concentrations above 2%.


Prevalence and determinants of blindness, low vision, deafness and major bone fractures among elderly Omani population of Nizwa Wilayat (Nizwa elderly population study-2005).
We conducted a survey in 2005 to estimate the prevalence and determinants of visual and hearing impairment in a population aged 60 years and above, from the Nizwa Wilayat of Oman. We also correlated them with major bone fracture. Cross-sectional survey. Vision was tested on Snellen's 'E' chart. Persons with vision less than 20/200 were reexamined by an ophthalmologist to find cause of impairment. Hearing was tested by a screening audiometer. Self-reported information on fracture of major bones was confirmed by review of case records. The prevalence, 95% confidence intervals (CI), and number of visually impaired individuals were calculated. Univariate method and parametric tests were used for analysis. We examined 1,639 (80.3%) Omani persons aged 60 years and above. The prevalence of blindness (vision less than 20/200 in the better eye) was 37.4% (95% CI 35.7-39.1). Blindness was significantly higher in females (Odd's Ratio = 2.1) but was similar in urban and rural Nizwa (OR = 0.73). The prevalence of vision impairment (20/60 to 10/200) was 36.0% (95% CI 34.3-37.7). Cataract was the principal cause in 50% of the blind. The prevalence of glaucoma, corneal opacity, and chronic trachoma was 3.1%, 66.8%, and 53.2%, respectively. Among participants, 36.1% had diabetes. Hearing impairment was noted in 33.5% and profound hearing loss was noted in 3.6% of participants. In the past year, 1.4% of participants had a major bone fracture. Visual and hearing impairment and blinding eye diseases were common among senior Omani citizens.


No Place Like Home: Cross-National Data Analysis of the Efficacy of Social Distancing During the COVID-19 Pandemic.
In the absence of a cure in the time of a pandemic, social distancing measures seem to be the most effective intervention to slow the spread of disease. Various simulation-based studies have been conducted to investigate the effectiveness of these measures. While those studies unanimously confirm the mitigating effect of social distancing on disease spread, the reported effectiveness varies from 10% to more than 90% reduction in the number of infections. This level of uncertainty is mostly due to the complex dynamics of epidemics and their time-variant parameters. However, real transactional data can reduce uncertainty and provide a less noisy picture of the effectiveness of social distancing. The aim of this paper was to integrate multiple transactional data sets (GPS mobility data from Google and Apple as well as disease statistics from the European Centre for Disease Prevention and Control) to study the role of social distancing policies in 26 countries and analyze the transmission rate of the coronavirus disease (COVID-19) pandemic over the course of 5 weeks. Relying on the susceptible-infected-recovered (SIR) model and official COVID-19 reports, we first calculated the weekly transmission rate (β) of COVID-19 in 26 countries for 5 consecutive weeks. Then, we integrated these data with the Google and Apple mobility data sets for the same time frame and used a machine learning approach to investigate the relationship between the mobility factors and β values. Gradient boosted trees regression analysis showed that changes in mobility patterns resulting from social distancing policies explain approximately 47% of the variation in the disease transmission rates. Consistent with simulation-based studies, real cross-national transactional data confirms the effectiveness of social distancing interventions in slowing the spread of COVID-19. In addition to providing less noisy and more generalizable support for the idea of social distancing, we provide specific insights for public health policy makers regarding locations that should be given higher priority for enforcing social distancing measures.


[Synergetic basis of the system of specialized medical care, specialized treatment and medical rehabilitation of minimally injured and minimally ill].
The article is devoted to analysis of the current system of specialized medical care, specialized treatment and medical rehabilitation of military casualties of minor nature. The author suggested a synergistic approach to combination of the given system with the aim of determination of development conception. Two main schemes of organization of specialized medical care are considered: medical care during the military conflict and local war; medical care during the regional and large-scale war. Taking into account the function of military field hospital for the treatment of walking wounded it was suggested to add a word combination "center of rehabilitation". The functions of the hospital are considered.


Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay.
Patients with rheumatoid arthritis (RA) can be successfully treated with tumor necrosis factor (TNF) inhibitors, including the monoclonal antibody adalimumab. Once in remission, a proportion of patients can successfully discontinue treatment, indicating that blocking TNF is no longer required for disease control. To explore the dynamics of circulating TNF during adalimumab treatment, we developed a competition enzyme-linked immunosorbent assay that can quantify TNF in the presence of large amounts of TNF inhibitor, i.e., a "drug-tolerant" assay. In 193 consecutive adalimumab-treated patients with RA, we demonstrated that circulating TNF increased in average of >50-fold upon treatment and reached a stable concentration in time for most patients. A similar increase in TNF was found in 30 healthy volunteers after one dose of adalimumab. This implies that TNF in circulation during anti-TNF treatment is not primarily associated with disease activity. During treatment, TNF was in complex with adalimumab and could be recovered as inactive 3:1 adalimumab-TNF complexes. No quantitative association was found between TNF and adalimumab concentrations. Low TNF concentrations at week 4 were associated with a higher frequency of antidrug antibodies (ADAs) at subsequent time points, less frequent methotrexate use at baseline, and less frequent remission after 52 weeks. Also in healthy volunteers, early low TNF concentrations are associated with ADAs. In conclusion, longitudinal TNF concentrations are mostly stable during adalimumab treatment and may therefore not predict successful treatment discontinuation. However, early low TNF is strongly associated with ADA formation and may be used as timely predictor of nonresponse toward adalimumab treatment.