Relationship between echocardiographic characteristics and cardiac biomarkers during long-distance trail running.
Even if the beneficial cardiovascular effects of moderate exercise are recognized, effects of prolonged and intense exercise are still debated. This study aims to detect cardiovascular changes associated with long endurance running by assessing the relationship between echocardiographic parameters and cardiac biomarkers during long-distance trail running. We performed a prospective observational study that included 20 participants who were all amateur runners (median age of 41 years old, still alive after a 7-year clinical follow-up) from 80-km trail running. All the participants underwent an echocardiographic examination and venous blood sampling before the race, at the intermediate refreshment checkpoints of the race (21st and 53rd km), and within 10 min after arrival. Mitral E/A velocity ratio and mitral TDI e' wave were significantly decreased at the 21st km to arrival (p < 0.05). Mitral S wave and global longitudinal strain (GLS) were significantly decreased from the 53rd km to arrival (p < 0.05 for 53rd and 80th km). As compared to baseline, T-troponin and NT-proBNP were significantly increased at the 21st km in all the participants, but T-troponin values were systematically increased above the significative threshold. Diastolic echocardiographic abnormalities were mainly observed among participants with highest NT-proBNP (> 77 ng.l-1) values at the 21st km. As compared to baseline, mitral e' wave was significantly decreased (-35%) in participants with highest values of NT-proBNP. Similarly, GLS was also depressed among participants with highest troponin values at the 53rd km (p = 0.01 for 53rd km and p = 0.04 for arrival). During the long-distance trail running, the early LV decrease in diastolic echocardiographic parameters is associated with increase in NT pro-BNP blood levels, and the decrease in LV systolic echocardiographic parameters later is associated with increase in T-troponin blood levels.


Molecular and clinical aspects of mitochondrial diabetes mellitus.
This review provides a compact overview on the contribution of mutations in mtDNA to the pathogenesis of diabetes mellitus, with emphasis on the A3243G mutation in the tRNA(Leu, UUR) gene. This mutation associates in most individuals with maternally inherited diabetes and deafness (MIDD) whereas in some other carriers the MELAS syndrome or a progressive kidney failure is seen. Possible pathogenic mechanisms are discussed especially the question why particular mutations in mtDNA associate with distinct clinical entities. Mutations in mtDNA can affect the ATP production, thereby leading to particular clinical phenotypes such as muscle weakness. On the other hand mtDNA mutations may also alter the intracellular concentration of mitochondrial metabolites which can act as signalling molecules, such as Ca or glutamate. This situation may contribute to the development of particular phenotypes that are associated with distinct mtDNA mutations.


Shattering Distribution for Active Learning.
Active learning (AL) aims to maximize the learning performance of the current hypothesis by drawing as few labels as possible from an input distribution. Generally, most existing AL algorithms prune the hypothesis set via querying labels of unlabeled samples and could be deemed as a hypothesis-pruning strategy. However, this process critically depends on the initial hypothesis and its subsequent updates. This article presents a distribution-shattering strategy without an estimation of hypotheses by shattering the number density of the input distribution. For any hypothesis class, we halve the number density of an input distribution to obtain a shattered distribution, which characterizes any hypothesis with a lower bound on VC dimension. Our analysis shows that sampling in a shattered distribution reduces label complexity and error disagreement. With this paradigm guarantee, in an input distribution, a Shattered Distribution-based AL (SDAL) algorithm is derived to continuously split the shattered distribution into a number of representative samples. An empirical evaluation of benchmark data sets further verifies the effectiveness of the halving and querying abilities of SDAL in real-world AL tasks with limited labels. Experiments on active querying with adversarial examples and noisy labels further verify our theoretical insights on the performance disagreement of the hypothesis-pruning and distribution-shattering strategies. Our code is available at https://github.com/XiaofengCao-MachineLearning/Shattering-Distribution-for-Active-Learning.


The economic costs of illness: a replication and update.
The economic burden resulting from illness, disability, and premature death is of major importance in the allocation of health care resources and in the evaluation of health research and programs. This article updates the 1963 and 1972 studies of the costs of illness. In 1980, the estimated total economic costs of illness were $455 billion: $211 billion for direct costs, $68 billion for morbidity, and $176 billion for mortality. Diseases of the circulatory system and injuries and poisonings were the most costly, with variations in the diagnostic distributions among the three types of costs and by age and sex.


COVID-19 in Portugal: a retrospective review of paediatric cases, hospital and PICU admissions in the first pandemic year.
COVID-19 is considered by WHO a pandemic with public health emergency repercussions. Children often develop a mild disease with good prognosis and the recognition of children at risk is essential to successfully manage paediatric COVID-19. Quality epidemiological surveillance data are required to characterise and assess the pandemic. Data on all reported paediatric COVID-19 cases, in Portugal, were retrospectively assessed from a fully anonymised dataset provided by the Directorate General for Health (DGS). Paediatric hospital admission results were obtained from the DGS vaccine recommendations and paediatric intensive care unit (PICU) admission results from the EPICENTRE.PT group. Reported cases and PICU admissions from March 2020 to February 2021 and hospital admissions between March and December 2020 were analysed. 92 051 COVID-19 cases were studied, 50.5% males, average age of 10.1 years, corresponding to 5.4% of children in Portugal. The most common symptoms were cough and fever, whereas gastrointestinal symptoms were infrequent. The most common comorbidity was asthma. A high rate of missing surveillance data was noticed, on presentation of disease and comorbidity variables, which warrants a cautious interpretation of results. Hospital admission was required in 0.93% of cases and PICU on 3.48 per 10 000 cases. PICU admission for Multisystem Inflammatory Syndrome in Children (MIS-C) was more frequent in children with no comorbidities and males, severe COVID-19 was rarer and occurred mainly in females and infants. Case fatality rate and mortality rates were low, 1.8 per 100 000 cases and 1.2 per 1 000 000 cases, respectively. The overall reported case incidence was 5.4 per 100 children and adolescents and <1% of cases required hospital admission. MIS-C was more frequent in patients with no comorbidities and males. Mortality and case fatality rates were low. Geographic adapted strategies, and information systems to facilitate surveillance are required to improve surveillance data quality.


Promoting and evaluating scientific rigour in qualitative research.
This article explores perspectives on qualitative research and the variety of views concerning rigour in the research process. Evaluating and ensuring the quality of research are essential considerations for practitioners who are appraising evidence to inform their practice or research. Several criteria and principles for evaluating quality in qualitative research are presented, recognising that their application in practice is influenced by the qualitative methodology used. The article examines a range of techniques that a qualitative researcher can use to promote rigour and apply it to practice.


Silver lampreys (Ichthyomyzon unicuspis) lack a gonadotropin-releasing hormone- and FMRFamide-immunoreactive terminal nerve.
The terminal nerve is a ganglionated cranial nerve with peripheral processes that enter the nasal cavity and centrally directed processes that enter the forebrain. Members of all classes of gnathostomes have been found to possess a terminal nerve, some components of which demonstrate immunoreactivity to the peptides Phe-Met-Arg-Phe-NH2 (FMRFamide) and gonadotropin-releasing hormone (GnRH). To explore the possibility that lampreys possess a terminal nerve, we examined the distribution of these peptides in the silver lamprey, Ichthyomyzon unicuspis, by using antisera to FMRFamide and to four forms of GnRH. We found cells with FMRFamide-like immunoreactivity in the preoptic area and the isthmal gray region of the mesencephalon, and found labeled fibers throughout the preoptic-infundibular region. Occasional labeled fibers were scattered through many regions of the brain, including the optic nerve and olfactory bulb; however, unlike species that possess a terminal nerve, lampreys have no immunoreactive cells or fibers in the olfactory nerve or nasal epithelia. In addition, we observed GnRH-immunoreactive cell bodies in the preoptic area of all animals and in the ventral hypothalamus of one individual. Most of the labeled fibers extended ventrally to the hypothalamus, with other fibers extending throughout the striatum and hypothalamic-neurohypophyseal region. A few fibers in other regions, including the optic nerve, were also labeled; we detected no immunoreactivity in the olfactory bulb, olfactory nerve, or nasal epithelia. The use of different GnRH antisera resulted in remarkably similar patterns of labeling of both cells and fibers. In summary, we did not observe either GnRH or FMRFamide-like immunoreactivity in the olfactory regions that represent the typical path of terminal nerve fibers, nor were we able to locate a terminal nerve ganglion. We conclude that lampreys may lack a terminal nerve, and that the previously described fiber bundle extending from the nasal sac to the ventral forebrain may constitute an extra-bulbar olfactory pathway.


Role of ethylene and abscisic acid in physicochemical modifications during melon ripening.
Hormonal metabolism associated with fruit ripening in two cantaloupe muskmelon cultivars, Talma and Manta, has been studied. The ethylene crisis began on day 33 after fruit set, reaching the maximum values of internal ethylene concentration and ethylene production rate on day 35 after fruit set. This was the optimum moment for consumption as shown by the higher content in soluble solids, ripening index, sensory analysis, and color parameter values. The b parameter and the b/a quotient values in peel were good indicators of the maturity stage, the optimum moment for harvesting being about day 33 after fruit set (when autocatalytic ethylene synthesis has begun), with values of 20 and 5 for the b parameter and b/a quotient, respectively. In both cultivars, free 1-aminocyclopropane-1-carboxylic acid (ACC) content increased until day 35 after fruit set and conjugated ACC increased in postclimacterium. The increase in both ACC-synthase and ACC-oxidase activities together could be responsible for the climacteric ethylene production. Significant differences in the abscisic acid evolution in Talma and Manta cultivars were reached, and also a possible stimulation of ethylene by this hormone could be established.


[Potential challenges for large-scale uses of RTS, S/AS01 vaccine in malaria-endemic areas].
RTS, S/AS01 vaccine has recently been recommended by the WHO for large-scale uses in malaria-endemic areas, which is a milestone in the history of the fight against parasitic infections. Nevertheless, RTS, S/AS01 vaccine is not perfect. Hereby, the shortages of RTS, S/AS01 malaria vaccine were discussed, and the potential challenges during the research and development of next-generation malaria vaccines were analyzed.


Genome-wide association analysis of panicle exsertion and uppermost internode in rice (Oryza sativa L.).
Rice (Oryza sativa L.) yield is seriously influenced by panicle exsertion (PE) and the uppermost internode (UI) through panicle enclosure or energy transport during grain-filling stages. We evaluated the traits of PE and UI of 205 rice accessions in two independent environments and performed genome-wide association (GWAS) to explore the key genes controlling PE and UI, which could be used to improve panicle enclosure in rice breeding. In this study, extensive genetic variation was found in both PE and UI among the 205 rice accessions, and 10.7% of accessions had panicle enclosure (PE/UI ≤ 0). Correlation analysis revealed that PE was significantly positively correlated with 1000-grain weight (1000-GW) but negatively correlated with heading date (HD), and UI was significantly positively correlated with HD but no significantly correlated with 1000-GW. A total of 22 and 24 quantitative trait loci (QTLs) were identified for PE and UI using GWAS, respectively. Eight loci for PE and nine loci for UI were simultaneously detected both in 2015 and in 2016, seven loci had adjacent physical positions between PE and UI, and ten loci for PE and seven loci for UI were located in previously reported QTLs. Further, we identified the CYP734A4 gene, encoding a cytochrome P450 monooxygenase, and the OsLIS-L1 gene, encoding a lissencephaly type-1-like protein, as causal genes for qPE14 and qUI14, and for qPE19, respectively. PE and UI were both significantly shorter in these two genes' mutants than in WT. Allelic Hap.1/2/4 of CYP734A4 and Hap.1/2/4 of OsLIS-L1 increased PE, UI, PE/UI, and 1000-GW, but Hap.3 of CYP734A4 and Hap.3 of OsLIS-L1 reduced them. In addition, six candidate genes were also detected for four key novel loci, qPE16, qPE21, qUI1, and qUI18, that seemed to be related to PE and UI. Our results provide new information on the genetic architecture of PE and UI in rice, confirming that the CYP734A4 and OsLIS-L1 genes participate in PE and UI regulation, which could improve our understanding of the regulatory mechanism of PE and UI for rice breeding in the future.


The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase AhpD, a potential target for antitubercular drug design.
The resistance of Mycobacterium tuberculosis to isoniazid is commonly linked to inactivation of a catalase-peroxidase, KatG, that converts isoniazid to its biologically active form. Loss of KatG is associated with elevated expression of the alkylhydroperoxidases AhpC and AhpD. AhpD has no sequence identity with AhpC or other proteins but has alkylhydroperoxidase activity and possibly additional physiological activities. The alkylhydroperoxidase activity, in the absence of KatG, provides an important antioxidant defense. We have determined the M. tuberculosis AhpD structure to a resolution of 1.9 A. The protein is a trimer in a symmetrical cloverleaf arrangement. Each subunit exhibits a new all-helical protein fold in which the two catalytic sulfhydryl groups, Cys-130 and Cys-133, are located near a central cavity in the trimer. The structure supports a mechanism for the alkylhydroperoxidase activity in which Cys-133 is deprotonated by a distant glutamic acid via the relay action of His-137 and a water molecule. The cysteine then reacts with the peroxide to give a sulfenic acid that subsequently forms a disulfide bond with Cys-130. The crystal structure of AhpD identifies a new protein fold relevant to members of this protein family in other organisms. The structural details constitute a potential platform for the design of inhibitors of potential utility as antitubercular agents and suggest that AhpD may have disulfide exchange properties of importance in other areas of M. tuberculosis biology.


Skeletal atavism in a miniature horse.
An 8-month-old miniature horse filly was presented for evaluation of severe rotational and angular limb deformities of the thoracic and pelvic limbs. On radiographic examination, complete ulnas and fibulas were identified. These findings are consistent with a condition previously described as a form of atavism. The term atavism is used to describe the reappearance of a trait or character that was seen in all earlier evolutionary specimens of a particular species, but has not been seen in recent ancestors. The atavistic traits of complete ulnas and fibulas have previously been described in Welsh and Shetland Ponies, all of which had severe rotational and angular limb deformities. In this horse, bilateral osteochondritis dissecans of the medial trochlear ridge of the talii were also identified. To the authors' knowledge, this is the first report of the atavistic traits of complete ulnas and fibulas seen in the miniature horse.


FK506 lacks the ability to inhibit expression of interleukin-2 receptor beta-chain on human lymphocytes.
Proliferation of T-lymphocytes is induced by interleukin-2 binding to the interleukin-2 receptor. This receptor consists of an alpha and a beta chain. FK506 is a new immunosuppressant known to inhibit synthesis of interleukin 2 and expression of the membrane bound alpha chain. In this study we show that FK506 does not suppress the expression of the beta chain on human lymphocytes, in the concentration range 1 pM to 1 microM, as measured by flow cytometry.


[Food sensitivities of the digestive tract-Part 1: Food allergies].
Adverse reactions to food affect approximately one third of the population. They are based on very different mechanisms and are divided into food intolerances, which manifest mainly in the gastrointestinal tract, and food allergies, which can also cause extraintestinal symptoms and have an immunological genesis. The most common food allergies in adults are pollen-associated allergies to cereals or pome and stone fruits, while allergies to peanut, milk and egg are particularly common in children. The diagnostics of food allergies are complex and therapy is primarily based on targeted elimination diets. This advanced education article focuses on food allergies with gastrointestinal symptoms.


Approach to a Patient with Stroke After Flying.
Arriving at a definitive diagnosis in case of a patient with neurological symptoms after a low altitude flight is very critical, while at the same time presenting a dilemma in aeromedical decision making. Symptoms of stroke can closely mimic those of neurologic manifestations of decompression sickness. This paper discusses the approach to a case of a 28-year-old male helicopter passenger who developed left-sided numbness of the body after a 1.5 h flight at 13,000 feet altitude and was hospitalized with the diagnosis of transient ischemic attack.


Reaction of rat pulp tissue to Carisolv 'new gel'--a histocytological evaluation.
This study was an histological examination of pulp tissue exposed to Carisolv 'new gel' after 1 to 28 days. An occlusal cavity was prepared in 64 caries-free molar teeth of 16 Wistar rats. The roofs of the pulp chambers were perforated and Carisolv 'new gel' solution was placed onto the exposed pulps of 32 molar teeth for 20 minutes. Thirty-two contralateral molar teeth served as controls and were coated with an inert liquid containing isotonic saline solution and carmellose for 20 minutes as well. The pulps of all teeth were capped with Ca(OH)2 and the cavities were filled with a flowable composite in combination with a self-etching dentine adhesive. The animals were sacrificed after 1, 3, 7 and 28 days. Eight teeth per group and the time period were histologically examined, scored, and statistically evaluated (Wilcoxon-test). The results showed no statistically significant differences between the Carisolv group and the control group (p > 0.05). The observed pulp reaction was essentially the same as those reported in the past being typical for the effect of calcium hydroxide as a direct pulp capping agent. Compared to Ca(OH)2, Carisolv 'new gel' did not cause any different or additional pulp reaction in healthy teeth.


Hemostatic dressings for the first responder: a review.
The military is interested in finding a hemostatic dressing that is effective in controlling hemorrhage from combat wounds, relatively inexpensive, and easy to transport. The fibrin dressing has existed for decades, but the military has been reluctant to use the dressing because it is not Food and Drug Administration approved, fairly expensive, and difficult to apply on certain wounds. Newer dressings such as the microporous polysaccharide hemosphere (TraumaDEX), mineral zeolite (QuikClot), poly-N-acetylglucosamine (HemCon), and microporous hydrogel-forming polyacrylamide (BioHemostat) dressings have addressed these deficiencies in that they are relatively inexpensive, easy to transport, and easy to apply. However, the effectiveness of these new dressings on wounds sustained in combat is still questionable according to studies and anecdotal reports from Operation Iraqi Freedom. More research is needed to draw definite conclusions about the effectiveness of these dressings in a combat setting.


Estimation of operators' fatigue using optical methods for determination of pupil activity.
The purpose of this study was to develop and initially validate an objective, yet quick, method for assessment of human fatigue. This aim can be achieved by the use of an optical, non-contact method of analysis of pupil activity. The study involved 2 phenomena typical for the behavior of the human pupil: pupillary reflex and pupillary movements. The 1st phenomenon is related to the pupillary light reflex (PLR), which presents the results of physiological adaptation mechanisms of the human eye. The pupillary unrest index (PUI) is an additional parameter referring to the tendency for instability of the pupil. Indicators of these 2 mechanisms were assessed under the same experimental laboratory conditions. Assessment was conducted on a group of volunteers (N = 10) during 4 controlled series of measurements performed at night. Pupillary reflex parameters associated with PLR and pupillary unrest index (PUI) were recorded using F²D Fit-For-Duty, a commercially available system made by AMTech Pupilknowlogy GmbH. Baseline pupil diameter, oscillations, reflex latency, maximum reaction time, pupil constriction time, pupil dilation time, and constriction amplitude were recorded. As a result of the study, we were able to demonstrate correlation and confirm the usefulness of PLR and PST methods in the assessment of sleep deprivation. Parameters of PLR that may indicate human fatigue were identified. The effect of light impulse sequences on the dynamics of pupillary reflex and the relationship between PUI (pupillary unrest index) measurement duration and sleepiness assessment validity, were assessed. The results of the pilot studies were sufficient to develop minimum requirements for a PLR sensor that would be capable of estimating the level of fatigue with accuracy of a PUI method, but at a 5 times faster rate.


Initial experience in the use of integrated electroanatomic mapping with three-dimensional MR/CT images to guide catheter ablation of atrial fibrillation.
No prior studies have reported the use of integrated electroanatomic mapping with preacquired magnetic resonance/computed tomographic (MR/CT) images to guide catheter ablation of atrial fibrillation (AF) in a series of patients. Sixteen consecutive patients with drug-refractory AF underwent catheter ablation under the guidance of a three-dimensional (3D) electroanatomic mapping system (Carto, Biosense Webster, Inc., Diamond Bar, CA, USA). Gadolinium-enhanced MR (n = 8) or contrast-enhanced high-resolution CT (n = 8) imaging was performed within 1 day prior to the ablation procedures. Using a novel software package (CartoMerge, Biosense Webster, Inc.), the left atrium (LA) with pulmonary veins (PVs) was segmented and extracted for image registration. The segmented 3D MR/CT LA reconstruction was accurately registered to the real-time mapping space with a combination of landmark registration and surface registration. The registered 3D MR/CT LA reconstruction was successfully used to guide deployment of RF applications encircling the PVs. Upon completion of the circumferential lesions around the PVs, 32% of the PVs were electrically isolated. Guided by a circular mapping catheter, the remaining PVs were disconnected from the LA using a segmental approach. The distance between the surface of the registered 3D MR/CT LA reconstruction and multiple electroanatomic map points was 3.05 +/- 0.41 mm. No complications were observed. Three-dimensional MR/CT images can be successfully extracted and registered to anatomically guided clinical AF ablations. The display of detailed and accurate anatomic information during the procedure enables tailored RF ablation to individual PV and LA anatomy.


Probing amphotericin B single channel activity by membrane dipole modifiers.
The effects of dipole modifiers and their structural analogs on the single channel activity of amphotericin B in sterol-containing planar phosphocholine membranes are studied. It is shown that the addition of phloretin in solutions bathing membranes containing cholesterol or ergosterol decreases the conductance of single amphotericin B channels. Quercetin decreases the channel conductance in cholesterol-containing bilayers while it does not affect the channel conductance in ergosterol-containing membranes. It is demonstrated that the insertion of styryl dyes, such as RH 421, RH 237 or RH 160, in bilayers with either cholesterol or ergosterol leads to the increase of the current amplitude of amphotericin B pores. Introduction of 5α-androstan-3β-ol into a membrane-forming solution increases the amphotericin B channel conductance in a concentration-dependent manner. All the effects are likely to be attributed to the influence of the membrane dipole potential on the conductance of single amphotericin B channels. However, specific interactions of some dipole modifiers with polyene-sterol complexes might also contribute to the activity of single amphotericin B pores. It has been shown that the channel dwell time increases with increasing sterol concentration, and it is higher for cholesterol-containing membranes than for bilayers including ergosterol, 6-ketocholestanol, 7-ketocholestanol or 5α-androstan-3β-ol. These findings suggest that the processes of association/dissociation of channel forming molecules depend on the membrane fluidity.


Herpes simplex virus type 2 (HSV-2) Western blot confirmatory testing among men testing positive for HSV-2 using the focus enzyme-linked immunosorbent assay in a sexually transmitted disease clinic.
The objective of this study was to define the positive predictive value (PPV) of the Focus herpes simplex virus type 2 (HSV-2) enzyme-linked immunosorbent assay (ELISA) in a low HSV-2 prevalence population and to develop a new test interpretation algorithm. HSV-2 Western blots were performed on sera from male sexually transmitted disease clinic patients testing HSV-2 ELISA-positive and used to define a new class of indeterminate HSV-2 ELISA result. HSV-2 Western blots were then prospectively performed on sequential sera with indeterminate HSV-2 ELISAs. Ninety-one (84%) of 108 HSV-2 ELISA-positive sera tested HSV-2 Western blot-positive. Western blot positivity was more common in men without herpes simplex virus type 1 (HSV-1) antibody than in those with HSV-1 antibody (93% vs 76%, P = 0.02) and in men with a history or clinical evidence of genital lesions (88% vs 80%, P = 0.30). Selectively raising the ELISA index value defining HSV-2 positivity from >1.1 to >or=3.0 either among HSV-1-positive men or among those without a history or clinical evidence of genital lesions increased the PPV to >or=93%. Prospective evaluation of an algorithm incorporating HSV-1 serostatus found that 11 of 70 persons with indeterminate HSV-2 ELISAs were Western blot-positive. Clinicians should consider selectively using a higher index value to define Focus ELISA HSV-2 positivity based on either HSV-1 serostatus or clinical circumstances.


Different aspects in functional dyspepsia.
Functional dyspepsia is still a puzzling medical problem. The causes are unknown, the pathogenetic mechanisms are uncertain, the management is controversial and medications are many times insufficient. The research so far has given conflicting results at all levels of investigation. This study represents an effort to collect all available data concerning the most disputed issues of functional dyspepsia. Topics regarding Helicobacter pylori eradication, pathophysiology, endoscopic and histologic correlations with symptomatology, the placebo effect and management options are presented following an evidence-based approach. Many articles, published in recent years, are discussed in order to obtain an overall insight of this peculiar symptom complex, named functional dyspepsia.


[Problems of co-financing of compulsory and voluntary medical insurance].
Health insurance issues are an important area of social interaction between different troupes of the population in the Russian Federation. This article discusses aspects of the current state of the market of medical voluntary and compulsory insurance in the Russian Federation. For this purpose, the article provides a comparative analysis of the concepts of "compulsory health insurance" and "voluntary health insurance". Also data are given on studying the market of medical insurance in Russia in recent times, and presents forecasts of researchers in the development of health insurance in the perspective up to 2020 in addition, the highlighted trends in the costs of financing health care. The problems of the Russian compulsory and voluntary medical insurance market and possible ways of their development are considered.


[Comparison of the effects of rapamycin-eluting stent implantation and coronary artery bypass grafting in treatment of patients with multi-vessel coronary disease].
To compare the clinical effects of rapamycin-eluting stent implantation and coronary artery bypass grafting (CABG) in treatment of the patients with multi-vessel coronary disease. From January 2002 to December 2004, 262 patients with multi-vessel coronary disease underwent CABG, and 250 age, clinical characteristics, and characteristics of coronary disease-matched patients chose to receive rapamycin-eluting stent implantation. 6-9 months after the treatment angiography of the coronary artery was conducted. All the patients were followed up for 19 +/- 14 months. The clinical outcomes were compared. No intra-operative death occurred in the rapamycin-eluting stent implantation group with an operation success rate of 100%, significantly higher than that of the CABG group with 9 intra-operative deaths and an operation success rate of 96.6% (P < 0.01). Three perioperative deaths occurred in the rapamycin-eluting stent implantation with a perioperative death rate of 1.2%, not significantly different from that of the CABG group (1.9% with 5 perioperative deaths). The total death rate during hospitalization of the rapamycin-eluting stent implantation group was 1.2%, significantly lower than that of the CABG group (5.3%, P < 0.05). The rate of in-hospital major adverse cardiac event (MACE) of the rapamycin-eluting stent implantation group was 1.6%, significantly lower than that of the CABG group (5.3%, P < 0.05). There was no significant difference in MACE rate and angina pectoris recurrence during follow-up and event-free survival rate between these 2 groups. A better treatment for the patients with multi-vessel coronary disease, rapamycin-eluting stent implantation has the clinical effects comparable to those of the CABG.


Superioralization of the Inferior Alveolar Nerve and Roofing for Extreme Atrophic Posterior Mandibular Ridges with Dental Implants.
Posterior mandibular ridges with extreme atrophy are usually combined with superficial location of the mental nerve and inferior alveolar nerves (IAN) and with a short residual mandibular ridge. As a result, dental implants cannot be placed in conjunction with IAN transposition alone. The aim of this paper is to introduce a new treatment approach to treat those patients. Eleven patients with 18 extreme atrophic posterior mandibular ridges characterized by superficial location of the IAN and short residual ridge had been treated during a 4-year period. The treatment approach included superior transposition of the IAN (IAN superioralization), 18 onlay bone block grafts harvested from the calvarial bone, implants placement through the block, and repositioning of the nerve under the onlay graft (IAN roofing). Patients were examined every 2-3 weeks; they received panoramic radiograph immediately after the surgery, at 4 months, at 6 months, and then once a year. Fixed prosthesis was performed after 4-5 months. The donor sites of the bone blocks healed very well. The increase of bone height ranged between 4 and 6 mm at the recipient sites, and 63 long implants were placed (10-13 mm). All the patients were hospitalized 1-3 days. The healing process was uneventful, and the nerve recovery lasted a maximal period of 6 months. The implant success and survival rates were 100%. All patients received fixed prosthesis. The functional outcomes were satisfactory with marked improvement in the quality of life of the patients. The follow-up period was 12-58 months. Superioralization of the IAN and roofing is a fast and predictable option to treat extremely atrophic posterior mandibular ridges with fixed prosthesis supported by dental implants.


Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia.
Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood−brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.


Three-dimensional self-assembling peptide matrix enhances the formation of embryoid bodies and their neuronal differentiation.
We have tailored the properties of a self-assembling peptide (SAP) matrix to direct embryonic stem cells towards neuronal differentiation by adopting a three-dimensional (3D) culture, matching mechanical strength with that of neural tissue, and incorporating fixed laminin-derived pentapeptide signals (IKVAV). We report here that such a matrix alone can induce mouse embryonic stem (ES) cells to first develop into embryoid body (EB) and increase their propensity for subsequent neuronal differentiation. Embryoid bodies were observed by day 5 of culture in SAP matrix. βIII-tubulin as an early neuronal commitment marker was more prominently detected in cells cultured in the matrix containing IKVAV signals. Interestingly, ES-derived cells did not display distinct neuron morphology within the 3D culture; however, 55 ± 10% of those cells within IKVAV conjugated matrix and 38 ± 6% of those within base matrix displayed higher potential towards neuronal differentiation after 7 days. When retrieved and recultured on a tissue culture plate, they exhibited extended neurite outgrowths and networks in the absence of any additional neuronal differentiation growth factor. The up-regulated expression of neuronal development markers (MAP2 and MeCP2) and the down-regulation of glial marker (GFAP) support that further neuronal differentiation takes place upon reculture. The results showed that an artificial matrix composed of designer SAPs could prompt the formation of EB and provides the cues favoring neuronal differentiation of ES cells.


COVID-19 in cancer patients on active systemic therapy - Outcomes from LMIC scenario with an emphasis on need for active treatment.
There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs). This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort. The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.


Hangover symptoms in Asian Americans with variations in the aldehyde dehydrogenase (ALDH2) gene.
Hangovers are not experienced by all people and whether they contribute to the development of alcoholism is unclear. One population that might provide some insight into the role of hangover in the etiology of alcohol use disorders is that of individuals of Asian heritage. Certain Asians have lower rates of alcohol use and alcoholism, findings associated with a mutation in the aldehyde dehydrogenase (ALDH2) gene. Asians with ALDH2*2 alleles drink less and are less likely to be alcoholic than Asians without this mutation. Following alcohol ingestion, they exhibit more intense reactions to alcohol and generate higher levels of the metabolite acetaldehyde. This study evaluated hangover symptoms in Asian Americans with variations in the ALDH2 gene. Men and women of Chinese, Japanese and Korean heritage (N = 140) were asked about their drinking history and a blood sample was collected for genotyping at the ALDH2 locus. Subjects used a Likert-type scale to estimate their severity of hangover and completed a 13-item hangover scale assessing the frequency of hangover symptoms during the previous 6 months. With abstainers (n = 17) excluded and with the effects of gender and recent drinking history controlled, ALDH2 genotype accounted for a significant amount of additional variability in the estimated severity of hangover score with a similar, but nonsignificant, trend for a five-item subscale score derived from the hangover scale. These results suggest that Asian Americans with ALDH2*2 alleles may experience more severe hangovers that may contribute, in part, to protection against the development of excessive or problematic drinking in this population.


Intercriteria Analysis to Diagnose the Reasons for Increased Fouling in a Commercial Ebullated Bed Vacuum Residue Hydrocracker.
The intercriteria analysis developed on the base of intuitionistic fuzziness and index matrices was applied to evaluate processing data of the LUKOIL Neftohim Burgas H-Oil ebullated bed vacuum residue hydrocracker with the aim of revealing the reasons for increased fouling registered during the 3rd cycle of the H-Oil hydrocracker. It was found that when the ratio of the ΔT of the 1st reactor to the ΔT of the 2nd reactor gets lower than 2.0, an excessive H-Oil equipment fouling occurs. The fouling was also found to be favored by processing of lower Conradson carbon content vacuum residual oils and increased throughput and depressed by increasing the dosage of the HCAT nanodispersed catalyst. The fouling in the atmospheric tower bottom section is facilitated by a lower aromatic content in the atmospheric tower bottom product. The addition of FCC slurry oil not only increases aromatic content but also dissolves some of the asphaltenes in the atmospheric residual hydrocracked oil and decreases its colloidal instability index. The fouling in the vacuum tower bottom section is facilitated by a higher saturate content in the VTB. Surprisingly, it was found that the asphaltene content in the VTB depresses the fouling rate. No relation was found of the sediment content in the hydrocracked residual oils measured by hot filtration tests and by the centrifuge method to the equipment fouling of the H-Oil hydrocracker.


Significantly Enhanced Electromechanical Performance of PDMS Crosslinked PVDF Hybrids.
Poly(vinylidene fluoride)-based ferroelectric polymers have large and tunable dielectric permittivity (εr), but rather high Young's modulus (Y), which limits its electromechanical response when used as actuators. In this work, a silicone oligomer involving amino groups is employed to crosslink a non-crystallized poly(vinylidene fluoride-chlorotrifluoroethylene) matrix bearing double bonds (P(VDF-CTFE-DB)) via addition reaction. Thanks to the flexible silicone molecules, the modulus of the hybrids is reduced over 30% when compared with the pristine matrix. Most interestingly, the εr of the hybrids is improved to nearly 100% higher than that of the matrix when the silicone content reaches 30 wt %. This may be due to the dilution effect of silicone molecules, which favors macromolecular chain rearrangement and dipole orientation of the hybrids under an applied electric field. As a result, electric-field activated displacements of the above hybrid increases to 0.73 mm from 0.48 mm of the matrix under 60 MV/m. The maximum electric field-induced thickness strain increases from 1% of the matrix to nearly 3% of the crosslinked hybrid. This work may provide a facile strategy to fabricate PVDF-based hybrids with enhanced electromechanical performance under low activating voltage.


Counselling and supporting parents of children with developmental delay: a research evaluation.
This paper describes an evaluation study of a home-based, family-focussed counselling scheme providing support for English-speaking and Bangladeshi families of children with intellectual or multiple disabilities. Mothers and children in the intervention groups showed significant and positive changes compared to randomly allocated controls. The greatest benefits were derived by the more deprived and initially less well-supported Bangladeshi families. Mothers changed positively in ratings of perceived support and family functioning, and in their constructions of their child, themselves, husbands and family relationships. Although systematic teaching was not included, their children also showed improvements in developmental progress and behaviour problems.


[Effects of aluminum ions on the mouse protein synthesis in vivo and in vitro].
Impact of aluminium ions on the translation process in mice liver, kidney, skeletal muscle and heart was investigated in vivo as well as on the protein synthesis in liver cell-free translation system in vitro. We find that at early stages of intoxication the effect of aluminium ions on protein synthesis in muscle tissues differs qualitatively from that one in liver or kidneys. Most noticeable aluminium-induced changes of protein synthesis in organs in vivo occur within the first 15-20 h after intoxication. We show that aluminium ions activates protein synthesis in liver and kidneys (at 8-16 h) while in skeletal muscle and heart does not. These results indirectly are supported by the data of experiments in vitro, which demonstrate that at low concentration aluminium ions activates protein synthesis in the cell-free translation system prepared from liver.


Quantitation of proteinuria by use of single random spot urine collection.
Measurements of protein to creatinine ratios in single voided urine samples were compared with 24 hour urinary protein excretion for quantification of proteinuria in 20 healthy control and 30 patients of various renal diseases. The range of proteinuria in study group was 1.46-6.0 g/day and renal function was stable in all the cases. An excellent correlation was found between the results obtained by this method and those from the standard 24 hours urine collection method in healthy controls (r = 0.99) and in patients with renal disease (r = 0.98). In our study urinary protein-creatinine ratio in control group was less than 0.2 in all cases and in study group was more than 3.0 except in one. The results of the present study indicate that the random urine protein-creatinine ratio is highly reliable test for quantification of proteinuria in children and has obvious advantage in term of time, cost and patients convenience.


Adolescent perceptions of risk and need for safer sexual behaviors after first human papillomavirus vaccination.
To (1) examine perceptions of risk of human papillomavirus (HPV) and other sexually transmitted infections (STIs), (2) examine perceived need for safer sexual behaviors, and (3) determine factors associated with less perceived need for safer sexual behaviors, all in the context of receiving the first HPV vaccination. Cross-sectional baseline analysis from an ongoing longitudinal cohort study. An urban hospital-based adolescent primary care clinic. Girls 13 to 21 years (for this article girls are defined as being aged 13 to 21 years) (n = 339) receiving their first HPV vaccination and their mothers (n = 235). (1) Girls' perceived risk of HPV after HPV vaccination, (2) girls' perceived risk of other STIs after vaccination, (3) girls' perceived need for continued safer sexual behaviors after vaccination, and (4) factors associated with girls' perception of less need for safer sexual behaviors. Mean age of girls was 16.8 years. Most participants (76.4%) were black, and 57.5% were sexually experienced. Girls perceived themselves to be at less risk for HPV than for other STIs after HPV vaccination (P < .001). Although most girls reported continued need for safer sexual behaviors, factors independently associated with perception of less need for safer sexual behaviors included adolescent factors (lower HPV and HPV vaccine knowledge and less concern about HPV) and maternal factors (lower HPV and HPV vaccine knowledge, physician as a source of HPV vaccine information, and lack of maternal communication about the HPV vaccine). Few adolescents perceived less need for safer sexual behaviors after the first HPV vaccination. Education about HPV vaccines and encouraging communication between girls and their mothers may prevent misperceptions among these adolescents.


Exposure to vibration and self-reported health complaints of riveters in the aircraft industry.
Workers using vibrating tools may experience neurological and vascular symptoms in the fingers and hands. The effect of vibration exposure on bone and joint disorders in the hand, arm and shoulder is less clear. In a cross-sectional study, riveters and controls in an aircraft company were investigated for vibration exposure and health complaints. Vibration measurements showed that frequency-weighted acceleration levels for riveting hammers and bucking bars ranged from 5.5 to 12.3 m s -2. The calculated equivalent frequency-weighted acceleration for a period of 4 h was the questionnaire survey 101 riveters reported statistically significant more complaints of pain and stiffness in their hands and arms when compared with 76 controls with no, or little, exposure to vibration. After 10 years of exposure statistically significant age-adjusted odds ratios (P less than 0.05) were found for vibration-induced white finger (VWF) (1.9) and pain or stiffness of the wrist (3.2). Although they were not statistically significant (0.05 less than P less than 0.10) odds ratios appreciably greater than 1 were found for numbness in fingers (1.6) and pain or stiffness in the elbow (1.6) and the shoulder (1.5), and these complaints were strongly associated with duration of exposure to vibration. With logistic regression the probabilities for a riveter of having symptoms of VWF after 10 and 20 years of exposure was estimated to be P = 0.18 and P = 0.29, respectively, which can be compared with the prevalences predicted by the dose-response relationship for VWF in ISO 5349, which are 10 and 30%. The results of this study suggest that exposure to vibration from working with impact power tools can contribute to complaints of pain and stiffness in the hand, arm and shoulder, and especially in the wrist.


X-linked recessive nephrolithiasis with renal failure.
Nephrolithiasis may occur as a consequence of a number of hereditary disorders. We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid. The pattern of inheritance was established by examining the patients and their records and interviewing family members. Selected members of the family were evaluated in detail, with measurements of erythrocyte cation fluxes and carbonic anhydrase (carbonate dehydratase) activity. The kindred consisted of 162 family members from six generations. All nine affected persons were male and appeared to have inherited the disease from their mothers. No affected man transmitted the gene to a son, but the daughters of affected men were carriers. The patients presented in childhood with calcium nephrolithiasis and proteinuria, with progression to nephrocalcinosis, urinary concentrating defects, and renal insufficiency. Renal biopsies revealed tubular atrophy, interstitial fibrosis, and glomerulosclerosis; the characteristic features of other forms of hereditary nephritis were absent. Abnormalities in the renal excretion of calcium, phosphate, potassium, and uric acid were found only in the adult members of the kindred, although renal biopsies were abnormal even in younger members. In one patient who has had a renal transplant for seven years, the disease has not recurred. This kindred manifested an X-linked recessive nephrolithiasis with renal failure, a new form of hereditary renal disease. Most of the identifiable physiologic abnormalities occurred after the development of nephrolithiasis and renal insufficiency and may not be of pathogenetic importance.


Numerical Evaluation on Analysis Methods of Trapping Site Density in Steels Based on Hydrogen Permeation Curve.
Hydrogen permeation techniques have been widely utilized to extract hydrogen effective diffusivity, as well as hydrogen trapping site characteristics in steels. Several methods have been proposed to examine reversible and irreversible trapping site characteristics. However, the inappropriate utilization of these simplified models, as well as incorrect value assignment to the key parameters, can result in several orders of magnitude difference in hydrogen trapping site density. Therefore, in order to evaluate these models and verify their application prerequisites, a serial of hydrogen permeation tests were numerically simulated and examined, separately considering reversible and irreversible hydrogen trapping sites. In the meantime, suggestions were given to conduct hydrogen permeation test more effectively, and evaluate hydrogen trapping site characteristics more precisely.


Selective excitatory actions of DNQX and CNQX in rat thalamic neurons.
The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from glutamatergic afferents from thalamocortical relay neurons and deep layer corticothalamic neurons, and they produce excitation via both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Quinoxaline derivatives [e.g., 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] have routinely been used as non-NMDA receptor antagonists over the last two decades. In this study, we examined whether quinoxaline derivatives alter the intrinsic properties of thalamic neurons in light of recent findings indicating that these compounds can alter neuronal excitability in hippocampal and cerebellar neurons via transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Whole cell recordings were obtained from TRN and ventrobasal (VB) thalamic relay neurons in vitro. DNQX and CNQX produced a consistent depolarization in all TRN neurons tested. The depolarization persisted in tetrodotoxin and low Ca²+/high Mg²+ conditions, suggesting a postsynaptic site of action. In contrast, DNQX and CNQX produced little or no change in VB thalamocortical relay neurons. The nonspecific ionotropic glutamate receptor antagonist, kynurenic acid, and the selective AMPAR antagonist, 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzenamine hydrochloride, blocked the DNQX-mediated depolarizations. Our results indicate that the DNQX- and CNQX-mediated depolarizations are mediated by AMPAR but not kainate receptors in TRN neurons. The AMPAR-positive allosteric modulator, trichloromethiazide, potentiated the DNQX-mediated depolarization in TRN neurons but did not unmask any excitatory actions of DNQX/CNQX in relay neurons. This selective action may not only reveal a differential TARP distribution among thalamic neurons but also may provide insight into distinct characteristics of AMPA receptors of thalamic neurons that could be exploited by future pharmacological development. Furthermore, these data suggest that quinoxaline derivatives could modulate synaptic transmission and alter neuronal excitability.


Characteristics of American young adults with increased risk for type 2 diabetes: a pilot study.
The purpose of the study was to examine the characteristics of American young adults with increased risk for type 2 diabetes (T2D). Participants ages 18 to 29, overweight/obese, and sedentary were recruited from the metro Atlanta area in the United States. Variables included demographics, anthropometric and clinical variables, and physical activity. Of 107 participants, 3 participants had undiagnosed diabetes and 1 participant did not complete the modifiable activity questionnaire. Thus, 103 young adults remained for the final data analysis. Most participants were females and African Americans. About 30% of participants had prediabetes, either impaired fasting glucose, an A1C of 5.7% to 6.4%, or both. Overall, prediabetes young adults were heavier and did less physical activity than Diabetes Prevention Program (DPP) trial participants. In addition, these young adults had a higher prevalence of parental T2D history and lower level of physical activity compared to young adults with normoglycemia. Physical activity and parent T2D history are key risk factors for identifying young adults with prediabetes. Multilevel strategies are necessary to raise awareness of diabetes risk and to prevent T2D in young adults.


[Hemodynamic factors associated with the development of hypertension].
Recent studies have focused on the prevention of hypertension among high-risk, nonhypertensive individuals. In this review, we present that the deficiency of renal sodium excretion, small artery remodeling, and arterial stiffening might be potent mechanisms underlying the development of hypertension. The changes of these hemodynamic factors cause to increase blood pressure, and increasing blood pressure would accelerate those changes again. To break the vicious circle, not only the management of risk factors such as diabetes, obesity, or smoking, but also the intervention with antihypertensive agents is considered as a useful and effective procedure.


Reliability of Isokinetic Strength Assessments of Knee and Hip Using the Biodex System 4 Dynamometer and Associations With Functional Strength in Healthy Children.
This study aimed to analyze the reliability of concentric isokinetic strength assessments (knee and hip) using the Biodex System 4 in healthy children and assess the association with functional strength tests (sit-to-stand [STS], lateral-step-up [LSU]). 19 children (6-12 years) were included. Knee and hip flexion and extension, and hip abduction and adduction were tested at 60 and 90°/s. Relative and absolute reliability at 60°/s tended to show better results compared to those at 90°/s. Intra class correlations (ICCs) of knee flexion and extension at 60°/s were good (0.79-0.89). For hip flexion, extension, abduction and adduction at 60°/s ICCs were moderate to good (0.53-0.83). The smallest detectable change (SDC) values (expressed in %) were highly variable. The SDC% for knee flexion and extension and hip abduction at 60°/s were around 50%. Positive associations were found between hip extension and abduction isokinetic strength and the STS test. Concentric isokinetic strength assessments in healthy children using the Biodex System 4 were found reliable for knee flexion and extension and hip abduction. Limited associations were found between concentric isokinetic strength tests and functional strength tests.


Effect of Triage Nurse Initiated Radiography Using the Ottawa Ankle Rules on Emergency Department Length of Stay at a Tertiary Centre.
To determine the effect of triage nurse initiated radiographs using the Ottawa Ankle Rules (OAR) on emergency department (ED) throughput. We hypothesized OAR use would reduce median ED length of stay (LOS) by 25 minutes or more. A randomized controlled trial was conducted at a tertiary centre ED with an annual census of over 90,000 patients. Adult patients presenting within 10 days of isolated blunt ankle trauma were eligible. Participants were randomly assigned to standard triage or OAR application by 15 explicitly trained triage nurses. Our primary outcome was ED LOS. Secondary outcomes included triage nurses' and patients' satisfaction. A power calculation indicated 142 patients were required. The Mann-Whitney U test was used to compare the medians between the two groups. Of 176 patients with blunt ankle injury screened, 146 were enrolled (83.0%); baseline characteristics in the two groups were similar. The median/mean ED LOS in the control and OAR groups were 128/143 minutes and 108/115 minutes respectively (median difference 20 minutes; p=0.003). Agreement in OAR use between emergency physicians and nurses was moderate (kappa 0.46/0.77 for foot/ankle rule components), and satisfaction of both nurses and participants was high. Triage nurse initiated radiography using OAR leads to a statistically significant decrease of 20 minutes in the median ED LOS at a tertiary care centre. The overall impact of implementing such a process is likely site-specific, and the decision to do so should involve consideration of the local context.


Ageism and kidney transplantation.
The growing shortage of deceased-donor kidneys and the rapid growth in the number of patients with end-stage renal failure aged 65 years and older is impacting the current policies for allocation of allografts. The utilitarian and egalitarian philosophies may clash in times of limited resources. Organ transplantation can be viewed as a microcosm concerning healthcare issues facing an aging population and limited resources. The limited resources in organ transplantation are not merely financial. The limits on supply of deceased-donor organs will force the transplant community to deal with allocation issues before the more general population faces other limits in health care. Our discussions may clarify some of the problems.


The Silver Lining of COVID-19: Estimation of Short-Term Health Impacts Due to Lockdown in the Yangtze River Delta Region, China.
The outbreak of COVID-19 in China has led to massive lockdowns in order to reduce the spread of the epidemic and control human-to-human transmission. Subsequent reductions in various anthropogenic activities have led to improved air quality during the lockdown. In this study, we apply a widely used exposure-response function to estimate the short-term health impacts associated with PM2.5 changes over the Yangtze River Delta (YRD) region due to COVID-19 lockdown. Concentrations of PM2.5 during lockdown period reduced by 22.9% to 54.0% compared to pre-lockdown level. Estimated PM2.5-related daily premature mortality during lockdown period is 895 (95% confidential interval: 637-1,081), which is 43.3% lower than pre-lockdown period and 46.5% lower compared with averages of 2017-2019. According to our calculation, total number of avoided premature death aassociated with PM2.5 reduction during the lockdown is estimated to be 42.4 thousand over the YRD region, with Shanghai, Wenzhou, Suzhou (Jiangsu province), Nanjing, and Nantong being the top five cities with largest health benefits. Avoided premature mortality is mostly contributed by reduced death associated with stroke (16.9 thousand, accounting for 40.0%), ischemic heart disease (14.0 thousand, 33.2%), and chronic obstructive pulmonary disease (7.6 thousand, 18.0%). Our calculations do not support or advocate any idea that pandemics produce a positive note to community health. We simply present health benefits from air pollution improvement due to large emission reductions from lowered human and industrial activities. Our results show that continuous efforts to improve air quality are essential to protect public health, especially over city-clusters with dense population.


Potential strategies against resistance to CAR T-cell therapy in haematological malignancies.
Chimeric antigen receptor (CAR) T-cell therapy is a rapidly developing method for adoptive immunotherapy of tumours in recent years. CAR T-cell therapies have demonstrated unprecedented efficacy in the treatment of patients with haematological malignancies. A 90% complete response (CR) rate has been reported in patients with advanced relapse or refractory acute lymphoblastic leukaemia, while >50% CR rates have been reported in cases of chronic lymphocytic leukaemia and partial B-cell lymphoma. Despite the high CR rates, a subset of the patients with complete remission still relapse. The mechanism of development of resistance is not clearly understood. Some patients have been reported to demonstrate antigen-positive relapse, whereas others show antigen-negative relapses. Patients who relapse following CAR T-cell therapy, have very poor prognosis and novel approaches to overcome resistance are required urgently. Herein, we have reviewed current literature and research that have investigated the strategies to overcome resistance to CAR T-cell therapy.


Study on Molecular Profiles of Staphylococcus aureus Strains: Spectrometric Approach.
Staphylococcus aureus remains a major health problem responsible for many epidemic outbreaks. Therefore, the development of efficient and rapid methods for studying molecular profiles of S. aureus strains for its further typing is in high demand. Among many techniques, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI TOF MS) represents a timely, cost-effective, and reliable strain typing approach, which is still rarely used due to insufficient knowledge about the impact of sample preparation and analysis conditions on the molecular profiles and strain classification efficiency of S. aureus. The aim of this study was to evaluate the effect of the culture conditions and matrix type on the differentiation of molecular profiles of various S. aureus strains via the MALDI TOF MS analysis and different computational methods. The analysis revealed that by changing the culture conditions, matrix type, as well as a statistical method, the differentiation of S. aureus strains can be significantly improved. Therefore, to accelerate the incorporation of the MALDI-based strain typing in routine laboratories, further studies on the standardization and searching of optimal conditions on a larger number of isolates and bacterial species are of great need.


[Persistence of Epstein-Barr virus antigens in gastric cancer: characteristic of inflammatory cellular reactions in tumor].
Is to establish the relationship between the persistence of viral antigens of the Epstein-Barr virus (EBV) and the cellular composition of the immune microenvironment of tumor tissue and the mucous membrane of peritumoral area in gastric cancer. We used samples of surgical material from 55 patients with a verified diagnosis of gastric cancer. The expression of CD4, CD8, CD68, CD1a and LMP-1 was assessed. The results were assessed by the morphometric method. We selected three fields of view (magnification x200) in tumor tissue and in peritumoral areas separately and counted an absolute number of cells with positive staining with further calculation of the average number of cells and the median. LMP-1-negative tumors with LMP-1 expression in epithelium of peritumoral area were characterized by the highest density of CD4+ lymphocyte infiltration in the central part of the tumor; the highest density of CD8+ lymphocyte infiltration in the mucous membrane of peritumoral area (p=0.0190); the highest density of infiltration by macrophages in the mucous membrane of peritumoral area (p=0.2492); the highest density of infiltration by CD1a+ cells in the mucous membrane of peritumoral area (p=0.1503). The highest density of infiltration with CD1a+ cells was characteristic for LMP-1-positive and LMP-1-negative tumors (p=0.0813). The persistence of the LMP-1 viral antigen in the glandular epithelium of the peritumoral area in our sample does not have a statistically significant effect on the prognosis of the disease (RR=1.7718; p=0.0885) but there is a tendency towards a negative predictive value. High density of infiltration of glandular epithelium of peritumoral area with the expression of LMP-1 by CD4+ and CD8+ lymphocytes is most likely associated with the activation of the cellular immune response and may be one of the signs of the persistence of viral antigens. It was shown for the first time that the phenomenon of persistence of the LMP-1 viral antigen is characterized by a trend towards negative predictive value for patients with gastric cancer.


Low incidence of MYC/BCL2 double-hit in Burkitt lymphoma.
Translocations involving MYC are highly characteristic for Burkitt lymphoma (BL). BCL2 expression has also been found previously in about 10 to 20% of BL cases, and BCL2 translocation is a major mechanism for the deregulation of BCL2 expression in non-Hodgkin lymphomas. However, we know little about the incidence of MYC/BCL2 double-hit (DH) in BL. We examined BL cases to determine how frequently they contained BCL2 translocations in combination with MYC translocations using fluorescence in situ hybridization. We also determined the effect of BCL2 expression on clinical outcomes of BL. BCL2 translocations were detected in 3.5% (2/57 cases) of the cases, and BCL2 expression was detected in 33%. Two cases with BCL2 translocation also showed BCL2 expression. The incidence of BCL2 expression was significantly higher in patients 16 years of age and older (46%) than in patients under 16 years of age (6%). Among patients 16 years of age and older, we did not detect significant differences in overall survival with respect to BCL2 expression status. In conclusion, BCL2 translocation is a rare cytogenetic abnormality in BL, and BL probably accounts for only a small fraction of MYC/BCL2 DH lymphomas. BCL2 expression in BL is probably not associated with BCL2 translocations.


Two Functional Classes of Rod Bipolar Cells in the Healthy and Degenerated Optogenetically Treated Murine Retina.
Bipolar cells have become successful targets for optogenetic gene therapies that restore vision after photoreceptor degeneration. However, degeneration was shown to cause changes in neuronal connectivity and protein expression, which may impact the quality of synthetically restored signaling. Further, the expression of an optogenetic protein may alter passive membrane properties of bipolar cells affecting signal propagation. We here investigated the passive membrane properties of rod bipolar cells in three different systems, the healthy retina, the degenerated retina, and the degenerated retina expressing the optogenetic actuator Opto-mGluR6. We found that, based on the shape of their current-voltage relations, rod bipolar cells in healthy and degenerated retinas form two clear functional groups (type 1 and type 2 cells). Depolarizing the membrane potential changed recorded current-voltage curves from type 1 to type 2, confirming a single cell identity with two functional states. Expression of Opto-mGluR6 did not alter the passive properties of the rod bipolar cell. With progressing degeneration, dominant outward rectifying currents recorded in type 2 rod bipolar cells decreased significantly. We demonstrate that this is caused by a downregulation of BK channel expression in the degenerated retina. Since this BK conductance will normally recover the membrane potential after RBCs are excited by open TRPM1 channels, a loss in BK will decrease high-pass filtering at the rod bipolar cell level. A better understanding of the changes of bipolar cell physiology during retinal degeneration may pave the way to optimize future treatment strategies of blindness.


The gene encoding the alternative thymidylate synthase ThyX is regulated by sigma factor SigB in Corynebacterium glutamicum ATCC 13032.
Both ThyA and ThyX proteins catalyze the transfer of the methyl group from methylenetetrahydrofolate (CH(2) H(4) -folate) to dUMP, forming dTMP. To estimate the relative steady state expression levels of ThyA and ThyX, Western blot analysis was performed using ThyA or ThyX antiserum on total protein from the wild-type, ΔthyX, and thyX-complemented strains of Corynebacterium glutamicum. The level of ThyA decreased gradually during the stationary growth phase but that of ThyX was maintained steadily. Whereas the expression level of ThyA in a ΔsigB strain was comparable to that of the wild-type, the level of ThyX was significantly diminished in the deletion mutant and was restored to that of the wild-type in the complemented strain, indicating that the level of ThyX was regulated by SigB. Growth of the C. glutamicum ΔsigB strain was dependent upon coupling activity of dihydrofolate reductase (DHFR) with ThyA for the synthesis of thymidine, and thus showed sensitivity to the inhibition of DHFR by the experimental inhibitor, WR99210-HCl. These results suggested that the relative levels of ThyA and ThyX differ in response to different growth phases and that SigB is necessary for maintenance of the level of ThyX during transition into the stationary growth phase.


Increase of c-Fos and c-Jun expression in spinal and cranial motoneurons of the degenerating muscle mouse (Scn8a(dmu)).
The degenerating muscle (dmu) mouse harbors a loss-of-function mutation in the Scn8a gene, which encodes the alpha subunit of the voltage-gated sodium channel (VGSC) Na(V)1.6. The distribution of c-Fos and c-Jun was examined in spinal and cranial motoneurons of the dmu mouse. In the cervical spinal cord, trigeminal motor nucleus (Vm), facial nucleus (VII), dorsal motor nucleus of the vagus (X), and hypoglossal nucleus (XII) of wild-type mice, motoneurons expressed c-Fos and c-Jun-immunoreactivity. The immunoreactivity in wild-type mice was mostly weak and localized to the nucleus of these neurons whereas in the spinal cord and brain stem of dmu mice motoneurons showed intense c-Fos and c-Jun-immunoreactivity. The number of c-Fos-immunoreactive motoneurons was dramatically elevated in the cervical spinal cord (wild type, 4.8 +/- 1.0; dmu, 17.3 +/- 1.6), Vm (wild type, 76.2 +/- 21.6; dmu, 216.9 +/- 30.9), VII (wild type, 162.4 +/- 43.3; dmu, 533.3 +/- 41.2), and XII (wild type, 58.2 +/- 43.3; dmu, 150.9 +/- 25.7). The mutation also increased the number of c-Jun-immunoreactive motoneurons in the cervical spinal cord (wild type, 1.6 +/- 0.8; dmu, 12.1 +/- 2.1), Vm (wild type, 41.4 +/- 18.0; dmu, 123.1 +/- 11.7), and X (wild type, 39.1 +/- 10.7; dmu, 92.8 +/- 17.8). The increase of these transcription factors may be associated with the uncoordinated and excessive movement of forelimbs and degeneration of cardiac muscles in dmu mice.


Layered and integrated medical countermeasures against Burkholderia pseudomallei infections in C57BL/6 mice.
Burkholderia pseudomallei, the gram-negative bacterium that causes melioidosis, is notoriously difficult to treat with antibiotics. A significant effort has focused on identifying protective vaccine strategies to prevent melioidosis. However, when used as individual medical countermeasures both antibiotic treatments (therapeutics or post-exposure prophylaxes) and experimental vaccine strategies remain partially protective. Here we demonstrate that when used in combination, current vaccine strategies (recombinant protein subunits AhpC and/or Hcp1 plus capsular polysaccharide conjugated to CRM197 or the live attenuated vaccine strain B. pseudomallei 668 ΔilvI) and co-trimoxazole regimens can result in near uniform protection in a mouse model of melioidosis due to apparent synergy associated with distinct medical countermeasures. Our results demonstrated significant improvement when examining several suboptimal antibiotic regimens (e.g., 7-day antibiotic course started early after infection or 21-day antibiotic course with delayed initiation). Importantly, this combinatorial strategy worked similarly when either protein subunit or live attenuated vaccines were evaluated. Layered and integrated medical countermeasures will provide novel treatment options for melioidosis as well as diseases caused by other pathogens that are refractory to individual strategies, particularly in the case of engineered, emerging, or re-emerging bacterial biothreat agents.


P wave morphology in guiding the ablation strategy of focal atrial tachycardias and atrial flutter.
Focal atrial tachycardias arise preferentially from specific locations within the atria. Careful analysis of the P wave can provide useful information about the chamber and likely site of origin within that chamber. Macro-reentrant atrial flutter also tends to occur over a limited number of potential circuits. In this case, the ECG usually gives a guide to the chamber of origin, but unless it shows a specific morphology it is less useful in delineating the circuit involved. Nonetheless, prior knowledge of the likely chamber of origin helps to plan the ablation strategy.


SECURE BASE SCRIPT CONTENT EXPLAINS THE ASSOCIATION BETWEEN ATTACHMENT AVOIDANCE AND EMOTION-RELATED CONSTRUCTS IN PARENTS OF YOUNG CHILDREN.
The secure base script (SBS) framework is one method of assessing implicit internal working models of attachment; recently, researchers have applied this method to analyze narratives regarding relationship experiences. This study examines the associations between attachment avoidance and SBS content when parents recall a positive moment of connection between themselves and their children (relational savoring) as well as their association with parental emotion and reflective functioning (RF). Using a sample of parents (N = 155, 92% female) of young children (53% boys, Mage = 12.76 months), we found that parental attachment avoidance is inversely associated with SBS content during relational savoring, and that SBS content is an indirect effect explaining the association between attachment avoidance and postsavoring (positive and negative) emotion as well as avoidance and poststressor RF. Findings have implications for understanding attachment and parenting.


Acute myeloid leukemia: treatment over 60.
Undertreatment of older patients with acute myeloid leukemia (AML) can explain, in part, their inferior outcome when compared to that of younger patients. In agreement with the benefit seen by patients under age 60 from high-dose cytosine arabinoside (Ara-C), there are dose effects in the over 60s, in particular for daunorubicin, in induction treatment and for the duration of postremission treatment. The use of these effects can partly overcome the mostly unfavorable disease biology in older age AML, as expressed by the absence of favorable and the over-representation of adverse chromosomal abnormalities as well as the expression of drug resistance. We recommend an adequate dosage of 60 mg/m2 daunorubicin on 3 days in combination with standard dose Ara-C and 6-thioguanine given for induction and consolidation, and followed by a prolonged monthly maintenance chemotherapy for at least 1 year's duration. Further improvements in supportive care may help to deliver additional antileukemic cytotoxicity. As a novel approach, nonmyeloablative preparative regimens may open up the possibility of allogeneic transplantation for older patients with AML. Other new options like multidrug resistance modulators, antibody targeted therapies and molecular targeting are under clinical investigation. A questionnaire study in patients with AML showed that, according to patients' self-assessment, intensive and prolonged treatment did not result in a diminished quality of life. This finding did not vary by age, under or over 60 years. As the median age in this disease is more than 60 years, the adequate management of AML in older patients remains the major challenge.


Social Morbidity in Relation to Bowel Functional Outcomes and Quality of Life in Anorectal Malformations and Hirschsprung's Disease.
Anorectal malformations (ARMs) and Hirschsprung's disease (HD) are chronic bowel conditions associated with varying degrees of fecal incontinence. We aimed to discuss the contemporary status of social morbidity associated with ARMs and HD in the long term after contemporary treatments. The bowel functional outcomes of our recent institutional series up to adulthood were reviewed and compared for ARMs and HD. The Rintala score was used to evaluate bowel function, which includes an assessment of the social effects of the condition. In this study, the social outcomes in our population of patients with ARMs and HD were specifically analyzed in relation to the surveyed functional outcomes, our previously collected data on quality of life (QoL) and the current literature. Mild ARMs were associated with a minimal risk of social morbidity consistent with good outcomes. In severe ARMs and HD, social problems were reported steadily among all age groups studied. Impairment of domains of fecal control were present among 53 to 89% of patients with social problems, including frequent symptoms (>1/week) in up to 39%. Involuntary gas leakage contributed to social morbidity in 15 to 27%. Comparison with QoL data suggested that social morbidity experienced during childhood may continue to affect emotional domains of QoL in later life, despite improvements in bowel function by adulthood. Patients with severe ARMs and HD are at risk of social restrictions from impairment of bowel function despite contemporary surgical treatments. However, the QoL outcomes in adulthood may be more influenced by self-perceptions of illness formed from childhood than disease-specific factors. Strategies to reduce the psychological morbidity associated with these conditions that includes parental involvement from the outset may improve outcomes.


Postnatal cadmium exposure, neurodevelopment, and blood pressure in children at 2, 5, and 7 years of age.
Adverse health effects of cadmium in adults are well documented, but little is known about the neuropsychological effects of cadmium in children, and no studies of cadmium and blood pressure in children have been conducted. We examined the potential effects of low-level cadmium exposure on intelligence quotient, neuropsychological functions, behavior, and blood pressure among children, using blood cadmium as a measure of exposure. We used the data from a multicenter randomized clinical trial of lead-exposed children and analyzed blood cadmium concentrations using the whole blood samples collected when children were 2 years of age. We compared neuropsychological and behavioral scores at 2, 5, and 7 years of age by cadmium level and analyzed the relationship between blood cadmium levels at 2 years of age and systolic and diastolic blood pressure at 2, 5, and 7 years of age. The average cadmium concentration of these children was 0.21 microg/L, lower than for adults in the National Health and Nutrition Examination Survey (NHANES), but comparable to concentrations in children < 3 years of age in NHANES. Except for the California Verbal Learning Test for Children, there were no differences in test scores among children in different cadmium categories. For children with detectable pretreatment blood cadmium, after adjusting for a variety of covariates, general linear model analyses showed that at none of the three age points was the coefficient of cadmium on Mental Development Index or IQ statistically significant. Spline regression analysis suggested that behavioral problem scores at 5 and 7 years of age tended to increase with increasing blood cadmium, but the trend was not significant. We found no significant associations between blood cadmium levels and blood pressure. We found no significant associations between background blood cadmium levels at 2 years of age and neurodevelopmental end points and blood pressure at 2, 5, and 7 years of age. The neuropsychological or hypertensive effects from longer background exposures to cadmium need further study.


Examining the relation between posttraumatic stress disorder and suicidal ideation in an OEF/OIF veteran sample.
This study examined the relation between posttraumatic stress disorder (PTSD) and suicidal ideation among U.S. military veterans deployed during Operation Enduring Freedom and/or Operation Iraqi Freedom. Specific aims included investigation of (1) whether PTSD was associated with suicidal ideation after controlling for combat exposure and history of suicide attempt(s), (2) whether PTSD was associated with suicidal ideation absent a co-occurring depressive disorder (MDD) or alcohol use disorder (AUD), (3) whether co-occurring MDD or AUD increased risk of suicidal ideation among those with PTSD and (4) whether PTSD/MDD symptom clusters were differentially associated with suicidal ideation. Results pointed to unique effects associated with prior suicide attempt(s), PTSD and MDD. PTSD-diagnosed participants with co-occurring MDD or AUD were not significantly more likely to endorse suicidal ideation than PTSD-diagnosed participants without such comorbidity. The 'emotional numbing' cluster of PTSD symptoms and the 'cognitive-affective' cluster of MDD symptoms were uniquely associated with suicidal ideation.


Adolescent sexual behavior along the Trans-Africa Highway in Kenya.
To describe the demographic characteristics and HIV-related risk behaviors of adolescents frequenting truck stops along the Trans-Africa Highway in Kenya. A cross-sectional study of 200 adolescents (52% female) aged 15-19 years was conducted at the Malaba, Sachangwan and Mashinari truck stops in Kenya. A standardized questionnaire assessing the adolescents' demographic characteristics and sexual behavior was administered. Most (89%) of the adolescents interviewed were out of school. Their median monthly family income was Ksh1000 (US$25). Most felt that their families provided inadequate access to food (72%), clothing (70%) and pocket money (87%). Ninety-three per cent of girls and 87% of boys had ever had sexual intercourse and of these 54% of girls and 38% of boys had ever used a condom. Fifty-two per cent of the girls and 30% of the boys reported ever having had a sexually transmitted disease. Forty-six percent of girls reported usually having sex with truck drivers, 78% of girls reported usually exchanging sex for gifts or money and 59% of boys reported usually giving gifts or money for sex. Subjects engaging in these three risk behaviors were generally less likely to be in school, less likely to live with relatives and less likely to report getting along well with their parents. Adolescents at truck stops along the Trans-African Highway in Kenya appear to be at significant risk for HIV infection. In the absence of an immediate and wide-ranging intervention, these conditions are likely to facilitate the spread of HIV from truck drivers and sex workers to adolescents.


Extraction and physicochemical characterization of greater Lizardfish (Saurida tumbil) skin and bone gelatin.
Type A gelatins were extracted from skins and bones of lizardfish and analyzed to determine their functional and chemical properties. Lizardfish skin gelatin had ash content of 2.2 +/- 0.3% while bone gelatin had ash content of 12.2 +/- 0.2%. Gel strength was 159.1 +/- 14 and 135 +/- 7.9 g, respectively, for skin and bone gelatins compared to 224.3 +/- 7.7 g for porcine gelatin. Gelatin from skin exhibited higher viscosity and lower setting time than bone. Skin gelatin had higher imino acid content than bone gelatin. The total imino acid content was 21.71% and 19.83% for skin and bone, respectively. Both skin and bone gelatins contained more alpha chains than beta and gamma components. Both bone and skin gelatins also contained low molecular weight (< alpha) peptides. The differences in functional properties between the skin and bone gelatins appeared to be related to differences in amino acid composition and molecular weight distribution of the gelatins.


Analysis of potential of Napier grass, Vetiver and Equisetum plants for the treatment of domestic greywater using box-type constructed wetlands.
The management of wastewater generated as a byproduct of various human activities from agricultural, industrial, and domestic sectors is a matter of global concern today. Greywater is a class of wastewater generated from the domestic sector. Greywater management can be done effectively by treating greywater at the source itself. In this context, constructed wetlands (CWs) come handy with low-tech, environmental, and economic-friendly options. In the present study, box-type horizontal subsurface flow constructed wetlands were designed and the efficiency of Napier grass (Pennisetum purpureum), Vetiver (Vetiveria zizanioides), and Equisetum (Equisetum hyemale) were assessed in treating domestic greywater. There was a drastic significant increase in DO with 47.0% in Vetiver, 92.5% in Napier grass, and 97.2% in Equisetum. The average percent pollutant removal of some major parameters was 92.4% for turbidity, 92.7% for acidity, 81.3% for BOD, 91.0% for COD with Napier grass. In the case of Vetiver, the removal percent was 82.5% turbidity, 87.9% acidity, 81.8% BOD, and 92.9% COD. For Equisetum, the average pollutant removal efficiency varied with 94.6% turbidity, 91.4% acidity, 80.0% BOD, and 88.1%COD. The study thus proves the efficiency of all the three plants to be used in box-type constructed wetlands.


Forensic psychiatry in north Africa.
This is the first review of literature regarding forensic psychiatry in north Africa that analyzes diversity of practice in this region of the world and its impact on mental health patients dealing with the judicial system. The present study shows similarities and differences in various countries in north Africa. In fact, there are many more similarities than differences, because of a lack of resources, both in the mental health and in the judicial systems. The present study gives an overview of forensic psychiatry in north Africa during the past 40 years. This practice is not well organized, despite the fact that mental health legislation and human rights review bodies exist.


Somatostatin receptor imaging: predictive and prognostic considerations.
Compared with other imaging modalities and clinical investigation, the 111In-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean (+/- SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% (+/- 6%). 8 patients had < 50% and 10 had > 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discussed.


Household visitation during the COVID-19 pandemic.
The COVID-19 pandemic has posed novel risks related to the indoor mixing of individuals from different households and challenged policymakers to adequately regulate this behaviour. While in many cases household visits are necessary for the purpose of social care, they have been linked to broadening community transmission of the virus. In this study we propose a novel, privacy-preserving framework for the measurement of household visitation at national and regional scales, making use of passively collected mobility data. We implement this approach in England from January 2020 to May 2021. The measures expose significant spatial and temporal variation in household visitation patterns, impacted by both national and regional lockdown policies, and the rollout of the vaccination programme. The findings point to complex social processes unfolding differently over space and time, likely informed by variations in policy adherence, vaccine relaxation, and regional interventions.


Configurational Entropy Approach to the Kinetics of Glasses.
A kinetic theory of glasses is developed using equilibrium theory as a foundation. After establishing basic criteria for glass formation and the capability of the equilibrium entropy theory to describe the equilibrium aspects of glass formation, a minimal model for the glass kinetics is proposed. Our kinetic model is based on a trapping description of particle motion in which escapes from deep wells provide the rate-determining steps for motion. The formula derived for the zero frequency viscosity η (0,T) is log η (0,T) = B - AF(T)kT where F is the free energy and T the temperature. Contrast this to the Vogel-Fulcher law log η (0,T) = B + A/(T - Tc). A notable feature of our description is that even though the location of the equilibrium second-order transition in temperature-pressure space is given by the break in the entropy or volume curves the viscosity and its derivative are continuous through the transition. The new expression for η (0,T) has no singularity at a critical temperature Tc as in the Vogel-Fulcher law and the behavior reduces to the Arrhenius form in the glass region. Our formula for η (0,T) is discussed in the context of the concepts of strong and fragile glasses, and the experimentally observed connection of specific heat to relaxation response in a homologous series of polydimethylsiloxane is explained. The frequency and temperature dependencies of the complex viscosity η (ω< T), the diffusion coefficient D(ω< T), and the dielectric response ε (ω< T) are also obtained for our kinetic model and found to be consistent with stretched exponential behavior.


[Progressive myopia and posterior scleral reinforcement: retrospective studies].
We evaluated the long and middle terms results in a retrospective study of Posterior Scleral Reinforcement in progressive myopia. We discuss the inclusion criteria and the results in terms of refraction, visual acuity, axial length, intra-ocular pressure, complications and patient's subjective appreciation. The surgical procedure of Posterior Scleral Reinforcement stabilises the evolution of progressive myopia in time. A systemic prospective study is needed for more precisions on those first encouraging results.


Measuring the cost-effectiveness of hematopoietic growth factor therapy.
The increasing cost of and demand for health care have intensified the concern that some form of health care rationing is inevitable. Cost studies require the identification, measurement, and comparison of all significant positive and negative consequences of alternative interventions and may evaluate benefit value, effectiveness, and effect on quality or quantity of life. The hematopoietic growth factors (HGF) will have far-reaching effect on the practice of medicine and, therefore, the design of cost-effectiveness studies are critically important in assessing economic effect.


Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression.
Alterations within human chromosomal region 11p15.5 are associated with the Beckwith-Wiedemann syndrome (BWS) and predisposition to a variety of neoplasias, including Wilms' tumors (WTs), rhabdoid tumors and rhabdomyosarcomas. To identify candidate genes for 11p15. 5-related diseases we compared human genomic sequence with expressed sequence tag and protein databases from different organisms to discover evolutionarily conserved sequences. Herein we describe the identification and characterization of a novel human transcript related to a putative Caenorhabditis elegans protein and the trp (transient receptor potential) gene. The highest homologies are observed with the human TRPC7 and with melastatin 1 ( MLSN1 ), whose transcript is downregulated in metastatic melanomas. Other genes related to and interacting with the trp family include the Grc gene, which codes for a growth factor-regulated channel protein, and PKD1/PKD2, involved in polycystic kidney disease. The novel gene presented here (named MTR1 for MLSN1 - and TRP -related gene 1) resides between TSSC4 and KvLQT1. MTR1 is expressed as a 4.5 kb transcript in a variety of fetal and adult tissues. The putative open reading frame is encoded in 24 exons, one of which is alternatively spliced leading to two possible proteins of 872 or 1165 amino acids with several predicted membrane-spanning domains in both versions. MTR1 transcripts are present in a large proportion of WTs and rhabdomyosarcomas. RT-PCR analysis of somatic cell hybrids harboring a single human chromosome 11 demonstrated exclusive expression of MTR1 in cell lines carrying a paternal chromosome 11, indicating allele-specific inactivation of the maternal copy by genomic imprinting.


B-Lymphoblastic Leukemia in Patients With Chronic Lymphocytic Leukemia: A Report of Four Cases.
B-lymphoblastic leukemia (B-LBL) arising in patients with chronic lymphocytic leukemia (CLL) is exceedingly rare and poorly characterized. We describe four patients with CLL and concurrent or subsequent B-LBL diagnosed by morphologic, immunophenotypic, cytogenetic, and molecular analysis and reviewed the literature. In three patients, B-LBL followed CLL by 5 to 15 years, and in one patient, B-LBL was diagnosed simultaneously with CLL. In all cases, the CLL had a typical immunophenotype, and the B-LBL blasts showed an immature B-cell immunophenotype with expression of CD10, CD19, and TdT and absence of surface immunoglobulin. In two patients, B-LBL blasts harbored t(9;22)(q34;q11.2)/BCR-ABL1. We sequenced the IGHV genes in both CLL and B-LBL in two patients and showed that IGHV usage differed. Our data suggest that at least some cases of B-LBL arising in patients with CLL are independent, secondary neoplasms rather than a manifestation of histologic transformation.


[Interstitial Pneumonia Caused by Olaparib during Treatment of Breast Cancer-A Case Report].
The characteristic adverse events of olaparib, a PARP inhibitor, are nausea, vomiting, and anemia, and interstitial pneumonia is rarely reported. We report a case of interstitial pneumonia following the treatment of a metastatic breast cancer with olaparib. The patient was a 34-year-old woman. In March 2018, she was diagnosed with stage Ⅳ breast cancer(multiple lung metastases). She was treated with epirubicin and cyclophosphamide followed by paclitaxel. In November 2018, brain and spinal cord metastases were detected, and she was treated with radiation. In December 2018, a BRCA1 deleterious mutation was confirmed, and treatment with olaparib was initiated. Six weeks later, olaparib was discontinued due to anemia; it also caused interstitial pneumonia. The interstitial pneumonia resolved following multidisciplinary treatment during hospitalization. Subsequently, she was treated with cyclophosphamide/methotrexate/fluorouracil. It is necessary to consider interstitial pneumonia as an adverse effect of olaparib.