The Hotel Study-Clinical and Health Service Effectiveness in a Cohort of Homeless or Marginally Housed Persons.
The Hotel Study was initiated in Vancouver's Downtown East Side (DTES) neighborhood to investigate multimorbidity in homeless or marginally housed people. We evaluated the clinical effectiveness of existing, illness-specific treatment strategies and assessed the effectiveness of health care delivery for multimorbid illnesses. For context, we mapped the housing locations of patients presenting for 552,062 visits to the catchment hospital emergency department (2005-2013). Aggregate data on 22,519 apprehensions of mentally ill people were provided by the Vancouver Police Department (2009-2015). The primary strategy was a longitudinal cohort study of 375 people living in the DTES (2008-2015). We analysed mortality and evaluated the clinical and health service delivery effectiveness for infection with human immunodeficiency virus or hepatitis C virus, opioid dependence, and psychosis. Mapping confirmed the association between poverty and greater number of emergency visits related to substance use and mental illness. The annual change in police apprehensions did not differ between the DTES and other policing districts. During 1581 person-years of cohort observation, the standardized mortality ratio was 8.43 (95% confidence interval, 6.19 to 11.50). Physician visits were common (84.3% of participants over 6 months). Clinical treatment effectiveness was highest for HIV/AIDS, intermediate for opioid dependence, and lowest for psychosis. Health service delivery mechanisms provided examples of poor access, poor treatment adherence, and little effect on multimorbid illnesses. Clinical effectiveness was variable, and illness-specific service delivery appeared to have little effect on multimorbidity. New models of care may need to be implemented.


Initial parathyroid exploration: current trends in Australia.
An Australia-wide multicentre prospective study was undertaken to audit cases of initial parathyroid exploration between 1 January and 31 December 1992. One hundred and sixty-two cases were audited. The audit was designed to study pre-operative biochemical assessment, localization techniques and the technique of exploration. A pro forma audit form was circulated to all Australian surgeons known to perform parathyroid surgery. Eleven responded. Free serum ionized calcium (iCa) was measured in 30% of cases, with the majority of pre-operative calcium assays being performed using total serum calcium (tCa). In 40 cases (29%) pre-operative localization techniques were used. These proved inaccurate in 10 cases. The intra-operative technique of localization with methylene blue infusion was used in 11% of cases. All four glands were biopsied in 11% of cases. No deaths were reported and a postoperative morbidity rate of 3.1% was noted. Eighty-eight per cent of patients were discharged within 5 days of surgery with a third going home within 48 h of neck exploration surgery. Only one patient (0.6%) required re-exploration for persistent hypercalcaemia due to a second adenoma. The surgical treatment of hyperparathyroidism can be regarded as safe, with minimum morbidity in experienced hands. Pre-operative localization studies in initial parathyroid exploration are not indicated.


Prevalence and causes of low vision and blindness in Tehran Province, Iran.
To determine the prevalence and causes of blindness and low vision selected population at Tehran province, Iran in 2006. A population-based cross-sectional study was conducted in the rural and urban population of Tehran province, Iran. The study design was based on the World Health Organization (WHO) criteria and a pilot study. Multi-stage cluster random sampling method was used and sample size was calculated based on the distribution of population in Tehran province derived from the national census and estimated rate of blindness from the pilot study. Information was collected using a questionnaire filled after screening by optometrists and referral examinations by ophthalmologists. Categorization of blindness and low vision was based on the International Classification of Diseases version 10 (ICD-10). Overall, 11,975 subjects with mean age of 27.77 +/- 18.9 years participated (primary response rate of 90.4%). The prevalence of bilateral blindness was 1.09% (95% CI: 0.90-1.61%). There was a significant positive correlation with age (P < 0.001) but no significant difference by gender. The prevalence of low vision in both eyes was 4.04% (95% CI: 3.69-4.39%). The prevalence of bilateral low vision increased with age (P < 0.001) and was higher among females (OR = 1.42, 95% CI: 1.16-1.74). The leading causes of visual impairment were cataract (33.9%), amblyopia due to uncorrected refractive errors (22.7%), vitreo-retinal diseases (12.3%), corneal blindness (10%) and diabetic retinopathy (4.92%). The prevalence of blindness and low vision in Tehran province, Iran is similar to other developing countries. The majority of cases have treatable and/or preventable causes; reduction of blindness can be achieved by appropriate screening strategies.


Navigator, a new endemic genus of Cetoniinae (Coleoptera: Scarabaeidae) from Australia, with descriptions of two new species and behavioural studies.
The endemic flower beetle genus Navigator new genus (Coleoptera: Scarabaeidae: Cetoniinae: Schizorhinini) is described from Australia. Navigator contains species that are morphologically and behaviourally unusual when compared to the majority of other Australian flower beetles in several easily visible characters. A differential diagnosis with similar Australian schizorhinine genera and species is performed, and a key to its species is provided. Pseudoclithria fossor Lea, 1914 and Pseudoclithria ruficornis (Westwood, 1874) are moved to the genus Navigator, resulting in Navigator fossor new combination, which is designated as the type species, and Navigator ruficornis new combination. A lectotype is designated for Navigator fossor (Lea, 1914). We describe Navigator interior new species, from Central Australia and Navigator pixii new species, which occurs in Queensland and is the smallest Australian Schizorhinini known. Distribution information for all Navigator species is provided. Our observations of Navigator fossor and Navigator pixii show their larvae are free living in soil and feed on decaying leaves, which is the first time such behaviour is described in Australian cetoniines. We observe that three Navigator species are more tolerant of arid climate than most other Australian cetoniines, adults almost never visit flowers, and males are often in flight searching for sedentary females.


[Pre-operative care for cardiac surgery patients with cold antibody disorder, cryoglobulinaemia and cryofibrinogenemia].
We present an example of a patient with confirmed cold agglutinin disease who underwent cardiac surgery in hypothermia to illustrate a known fact that, when exposed to cold, cold agglutinins induce haemolysis of erythrocytes and that cryoglobulins and cryofibrinogens may, upon exposition to cold during a surgery under hypothermia, precipitate or gelify and thus increase plasma viscosity and damage microcirculation. Detailed immunological and haematological investigations in all patients awaiting cardiac surgery with a risk of developing hypothermia is not advantageous considering the low number of patients with clinical and laboratory signs of cold agglutinin disease, autoimmune haemolytic anaemia or paroxysmal cold haemoglobinuria and considering that these investigations, in addition, might not detect cryoglobulinaemia and cryofibrinogenemia. Identification of in-risk patients from the warning signs in the medical history, physical or basal laboratory testing who would subsequently undergo confirmatory investigations to verify the presence of these entities and define them accurately might be a potential solution to this clinical issue. Cardiac surgery strategy and peri-operative care should be tailored to the results of these investigations. Well-structured, practiced and functional cooperation between clinicians and laboratory personnel is a prerequisite for success in these circumstances.


Assessment of Spanish Food Consumption Patterns during COVID-19 Home Confinement.
People's eating habits and lifestyle can have a negative impact on health. In situations of difficulty or socioeconomic crisis, these habits tend to be modified, leading to unhealthy dietary patterns that result in an increase of chronic non-communicable diseases (NCDs). Previous studies have indicated that, due to the state of alarm imposed in Spain to combat the spread of COVID-19, an increase in the purchase of non-core products occurred, along with a decrease in the daily physical activity of the population. This could be a risk factor for COVID-19 infection. The objective of this observational study was to analyze the dietary pattern of the Spanish population during home confinement and to compare it with the pattern of habitual consumption collected in the last National Health Survey, analyzing the possible changes. More than half of the respondents in the sample increased their consumption of sweets and snacks during confinement, while the consumption of fresh products decreased. Most claimed to be emotionally hungry, leading to an increase in their daily energy intake. The stress and anxiety generated by confinement could be the cause of the increased consumption of products rich in sugars and saturated fats, which are associated with greater stress and anxiety.


A Method for Enhancing the Sensing Distance of a Fingerprint Sensor.
In this paper, we describe a method for improving the quality of fingerprint images at long sensing distances by reducing the fringe capacitance formed between a pixel and surrounding fingerprint patterns. Air-walls were applied to the glass attached to a fingerprint sensor for reducing the edge capacitance. Fingerprints and air-wall structures were modeled using a three-dimensional capacitance analysis tool. A prototype was fabricated by stacking glass layers with air-walls with a depth of 50 μm and a pitch of 50 μm on a silicon-type capacitive sensor. Using the results of simulations and prototype experiments, we confirmed that the proposed air-wall structure achieved high enough resolution to distinguish 2.5-lp/mm fingerprint patterns at a sensing distance of 300 μm or longer, and its contrast improved from 0.59 to 0.98.


Models of care for adolescent and young adult cancer programs.
This review draws on the experience of adolescent and young adult (AYA) cancer clinicians from Australia, the United States, and the United Kingdom to summarize common aspects of models of care implemented in their countries. The principles underpinning these models include patient- and family-focused care informed by an understanding of normal AYA development, enhancing existing adult or pediatric cancer services to meet the needs of AYA, and promoting collaboration between pediatric and adult oncologists. Common elements of AYA cancer care include establishing an AYA multidisciplinary team that integrates medical and psychosocial care, efforts to centralize complex care, providing access and equity for all AYA, promoting clinical trials, and helping facilitate transition to healthy survivorship. Several organizational approaches are described, noting that local program development depends on resources, infrastructure, and assessment of unmet needs within the region. The development of national networks provides opportunities for shared learning and approaches to evaluation.


Serotonin systems in the inner and outer plexiform layers of the vertebrate retina.
In retinas of certain nonmammalian vertebrate species such as frog, pigeon, and chick, serotonin appears to function as the neurotransmitter of a specific population of amacrine cells. Neurochemical and morphological studies have demonstrated high endogenous levels of 5-hydroxytryptamine (5-HT) as well as uptake, release, and receptor-binding activity restricted to the inner plexiform layer. In retinas from most mammalian species, uptake, release, and receptor-binding activity have also been localized to amacrine cell terminals in the inner plexiform layer. However, serotonin content in mammalian retinas is low, and attempts to localize the endogenous store of 5-HT have failed. Thus the status of serotonin as a candidate in mammalian retina is still open to question. Our more recent studies have revealed a light-sensitive serotonin system associated with photoreceptor terminals in retinas of Long-Evans rats. Uptake, synthesis, and release of [3H]serotonin have been demonstrated. Endogenous levels of 5-HT decrease in the dark and increase in the light. Electrophysiological studies are needed to illucidate the functional role(s) of serotonin within retinas of different species.


An anatomical fetal brain structure and a normal variant mimicking anomalies on routine neurosonographic imaging: report of two cases.
We present two cases in which an anatomical structure, the calcar avis, and a normal variant, a bifid choroid plexus, mimicked abnormalities on routine prenatal ultrasound examination. To the best of our knowledge these pitfalls have only been described in neonates. A familiarity with these false images is important to avoid erroneous diagnoses.


Invasion of Tilapia mossambica (cichlidae) viscera by the monogenean Enterogyrus cichlidarum.
The monopisthocotylean monogenean Enterogyrus cichlidarum, which normally inhabits the stomach and anterior intestinal lumina of tilapine cichlids, invaded the internal organs of juvenile Mozambique tilapia (Tilapia mossambica). Adult worms infected the intestinal mucosa, peritoneal cavity, liver, heart, blood vessels, swimbladder, and braincase. Most of the parasites were adults and contained eggs. Both adults and eggs incited a mononuclear inflammatory response. Infections were associated with chronic morbidity and mortality. Although affected fishes were overcrowded, the precise stress responsible for such an unusually invasive event is unknown.


Laparoscopic treatment of uterine myomas.
The treatment of leiomyomas of the uterus has traditionally been by laparotomy. Newer endoscopic instruments are enabling gynecologists to treat these common tumors with minimally invasive surgery, resulting in same day or overnight hospitalization and much shorter recovery times. The laparoscope is one of the endoscopic instruments that is allowing the to occur.


Using state administrative and pharmacy data bases to develop a clinical decision support tool for schizophrenia guidelines.
Administrative and pharmacy data bases represent a largely untapped resource for clinical decision support and quality improvement. In this study, we examined the feasibility of using New York State Office of Mental Health (NYSOMH) data bases to develop an automated clinical report to support implementation of schizophrenia guidelines. First we reviewed the structure of existing data bases for capacity and limitations in supporting guideline implementation. Second, we identified schizophrenia guideline recommendations and adherence measures that would be the focus of our implementation. Third, a preliminary report was programmed, based on operational definitions of the guideline recommendations. Finally, we developed user groups to define content and format of new reports, through an iterative process of field testing, feedback, and revision. Our experience suggests that administrative and pharmacy data bases, despite their limitations, can be used to develop guideline-based clinical decision support tools for schizophrenia with high physician acceptability.


Modulation of the catalytic activity of pyridoxal kinase by metallothionein.
Pyridoxal kinase displays high catalytic activity in the presence of metallothionein. The apoprotein of metallothionein as well as the peptide LYS-CYS-THR-CYS-CYS-ALA exert a strong inhibitory effect upon pyridoxal kinase by sequestering free Zn ions. Several steps intervene in the process of pyridoxal kinase activation, i.e. binding of Zn ions by ATP and interaction of Zn-ATP with the enzyme; but direct interaction between metallothionein and pyridoxal kinase (protein association) could not be detected by emission anisotropy measurements. Since the concentration of free Zn++ in mammalian tissues is lower than 10(-9)M, it is postulated that the concentration of metallothionein regulates the catalytic activity of pyridoxal kinase. The mechanism of reconstitution of the metalloenzyme yeast aldolase in the presence of metallothionein was also investigated.


Remodeling of the abdominal epithelial monolayer during the larva-pupa-adult transformation of Manduca.
During metamorphosis of insect epithelial monolayers, cells die, divide, and rearrange. In Drosophila undifferentiated diploid cells destined to form the adult cuticle of each abdominal segment segregate early in development from the surrounding polyploid larval epithelial cells of that segment as eight groups of diploid histoblast cells. The larval polyploid cells are programmed to die and be replaced by divisions and rearrangements of histoblast cells. By contrast, abdominal epithelial cells of Manduca larvae form a monolayer of cells representing different ploidy levels with no definitive segregation of diploid cells destined to form adult structures. These epithelial cells of mixed ploidy levels produce a thick smooth larval cuticle with sparsely distributed sensory bristles. Adult descendants of this larval monolayer produce a thinner cuticle with densely packed scale cells. The transition between these differentiated states of Manduca involves divisions of cells, changes in ploidy levels, and sorting of certain polyploid cells into circular rosette patches to minimize contacts of these polyploid cells with surrounding cells of equal or smaller size. Cells within the rosettes and some surrounding cells are destined to die and be replaced by remaining epithelial cells of uniform size and ploidy at pupa-adult apolysis.


Tongue-to-palate contact patterns and variability of four English consonants in an /i/ vowel environment.
Minimal data exist describing tongue-to-palate contact patterns and their variability in normal speakers of English. Consequently, the aims of the present study were to examine, using a comprehensive profile of data analysis, tongue-to-palate contact patterns and their variability in a group of ten normal speakers of English using the Reading Electropalatography3 (EPG3) system. Each speaker produced ten repetitions of the target words tea, leap, sea, and key following the carrier phrase 'I saw a ...'. Results revealed that the contact patterns produced exhibited similar characteristics to those described in earlier research. Additionally, the lateral approximant /i/ exhibited the highest degree of intra-subject variability with the alveolar fricative /s/ exhibiting the least. The results of this study are discussed in relation to existing normative data.


Loop-Mediated Isothermal Amplification Assay for Rapid Detection of Hypothetical Protein Gene in Escherichia Coli Clinical Isolates.
Escherichia coli is the most common pathogenic bacteria that frequently causes life-threatening opportunistic human infections, diarrhea, and septicemia in immunocompromised hosts. This study aimed to establish a loop-mediated isothermal amplification (LAMP) method for the rapid and sensitive detection of a hypothetical protein from an E. coli-specific gene (GenBank ID: 13702648). The gene was obtained through local and online BLAST, and specific primers were designed for this gene. Reaction conditions were optimized at 65ºC for 30 minutes and 80ºC for 2 minutes, whereas the reaction system contained 5.2 mM Mg2+, 8 U of Bst 2.0 DNA polymerase, 1.4 mM deoxyribonucleotide, and 0.2 and 1.6 µM of the outer and inner primers, respectively. The LAMP method was evaluated using 240 strains of E. coli and 150 strains of non-E. coli. Positive reactions were observed on all 240 strains of E. coli while all non-E. coli strains were negative. Plasmids with the specific gene and mice blood with E. coli were used for sensitivity analysis. The detection limit of LAMP was 100 bacterium/reaction. Results showed that the LAMP targeted to the hypothetical protein (GenBank ID: 13702648) is a fast, specific, sensitive, inexpensive, and suitable method for the detection of E. coli.


Evidence of the validity of the Food and Nutritional Security Scale for adolescents (ESANa).
This study aimed to develop a valid and reliable scale for assessing food and nutritional insecurity, specifically in adolescents. The initial version of the scale consisted of two subscales: perception of food insecurity and perception of nutritional security. The items were submitted to content analysis (n = 4) by a group of food and nutrition security experts, and semantic analysis (n = 20) by a group of adolescents conveniently sampled from the target population. After adjustments, the final version of the scale was applied to adolescent students (n = 425) aged 12 to 18 years (m = 14.32±0.96; CV = 6.7%). A two-factor model was the most appropriate after performing exploratory factor analysis. The subscales showed modest values of the alpha coefficient (0.69 and 0.60, respectively). Daily consumption of fruits, vegetables and soft drinks was significantly associated with higher scores in the food and nutrition security perception scale. Therefore, it is recommended to combine food access-based items with other aspects related to attitudes and behaviors towards healthy eating in order to achieve a more accurate picture of adolescent's needs and better guide public policies.


In-Home Monitoring Technology for Aging in Place: Scoping Review.
For successful aging-in-place strategy development, in-home monitoring technology is necessary as a new home modification strategy. Monitoring an older adult's daily physical activity at home can positively impact their health and well-being by providing valuable information about functional, cognitive, and social health status. However, it is questionable how these in-home monitoring technologies have changed the traditional residential environment. A comprehensive review of existing research findings should be utilized to characterize recent relative technologies and to inform design considerations. The main purpose of this study was to classify recent smart home technologies that monitor older adults' health and to architecturally describe these technologies as they are used in older adults' homes. The scoping review method was employed to identify key characteristics of in-home monitoring technologies for older adults. In June 2021, four databases, including Web of Science, IEEE Xplore, ACM Digital Library, and Scopus, were searched for peer-reviewed articles pertaining to smart home technologies used to monitor older adults' health in their homes. We used two search strings to retrieve articles: types of technology and types of users. For the title, abstract, and full-text screening, the inclusion criteria were original and peer-reviewed research written in English, and research on monitoring, detecting, recognizing, analyzing, or tracking human physical, emotional, and social behavior. The exclusion criteria included theoretical, conceptual, or review papers; studies on wearable systems; and qualitative research. This scoping review identified 30 studies published between June 2016 and 2021 providing overviews of in-home monitoring technologies, including (1) features of smart home technologies and (2) sensor locations and sensor data. First, we found six functions of in-home monitoring technology among the reviewed papers: daily activities, abnormal behaviors, cognitive impairment, falls, indoor person positioning, and sleep quality. Most of the research (n=27 articles) focused on functional monitoring and analysis, such as activities of daily living, instrumental activities of daily living, or falls among older adults; a few studies (n=3) covered social interaction monitoring. Second, this scoping review also found 16 types of sensor technologies. The most common data types encountered were passive infrared motion sensors (n=21) and contact sensors (n=19), which were used to monitor human behaviors such as bodily presence and time spent on activities. Specific locations for each sensor were also identified. This wide-ranging synthesis demonstrates that in-home monitoring technologies within older adults' homes play an essential role in aging in place, in that the technology monitors older adults' daily activities and identifies various health-related issues. This research provides a key summarization of in-home monitoring technologies that can be applied in senior housing for successful aging in place. These findings will be significant when developing home modification strategies or new senior housing.


Effects of Baytril, Tylosin and Tiamulin on avian mycoplasmas.
The minimum inhibitory concentration (MIC) of Baytril, Tylosin and Tiamulin for strains of Mycoplasma gallisepticum (MG) M. synoviae (MS), M. meleagridis (MM) and M. iowae (MI) and serovars were compared. In general the lowest MIC for MG, MS and MI was obtained with Baytril, while for MM both Baytril and Tiamulin gave the lowest MICs. Protection against mortality was best attained with Baytril for broiler chicks and poults but against prevention of growth depression Baytril was best for broiler chicks whilst Baytril and Tylosin were equally effective in poults. MG was recovered from fewer birds following treatment with Tiamulin and then Baytril in that order. Baytril also had a suppressive effect on the natural infection of MI in poults. Fewer poults showed rapid serum agglutination reactions to MG antigen following Baytril treatment than with the other antimicrobials. The tolerance of turkey embryos for Baytril was between 1 and 2 mg/ egg. Baytril reduced MG infection of turkey embryos.


Dichloroacetate reduces plasma lactate levels but does not reduce infarct size in rabbit myocardium.
Dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDHC), enhances postischemic mechanical recovery of isolated hearts. It is not known whether this is secondary to reduced infarction or preservation of contractile function in viable cardiomyocytes. This study investigated the effect of DCA on myocardial infarct size. Anesthetized open chest rabbits underwent regional coronary occlusion and reperfusion. DCA (300 mg/kg plus 150 mg/kg 1 h later) was administered intravenously either before occlusion (DCA-O; n = 8) or at reperfusion (DCA-R; n = 7). Control rabbits (n = 8) received saline vehicle. Myocardial PDHC activity was measured after administration of 300 mg/kg i.v. DCA in 10 separate rabbits. DCA reduced plasma lactate levels and increased PDHC activity by 76%, from 2.79 +/- .30 mumol/min.g-1 to 4.92 +/- .44 mumol/min.g-1 (p < .005). However, infarct size in DCA-treated animals was not significantly different from Control (60 +/- 5% DCA-O, 57 +/- 6% DCA-R, 58 +/- 7% Control). We conclude that stimulation of pyruvate dehydrogenase does not limit infarct size.


Decrease in tetanic tension elicited by beta-adrenergic stimulation.
The effect of beta-adrenergic stimulation on tetanic tension (TT), maximal rate of rise of tension (+TT) and phospholamban (PHL) phosphorylation were studied in the perfused rat heart. 3 x 10(-8) M isoproterenol perfused at different [Ca2+]o 0.25, 1.35 and 3.85 mM, significantly decreased TT while increased +TT and PHL phosphorylation at the three [Ca2+]o studied. Regression lines of the relationship between +TT and TT from individual data obtained at each [Ca2+]o in the presence and in the absence of isoproterenol, show that for the same level of +TT, TT is lower in the presence of isoproterenol, i.e. at high levels of PHL phosphorylation. The slopes of the lines were 0.137 s and 0.427 s (P less than 0.05) in the presence and absence of isoproterenol respectively. The decrease in TT produced by the beta-agonist can be attributed to its relaxant action prevailing over its inotropic effect and may represent the mechanical expression of the enhanced phosphorylation of phospholamban.


Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets.
To assess the ability to detect the neural canal opening (NCO) and its characteristics within three-dimensional (3-D) histomorphometric and 3-D spectral domain optical coherence tomography (SD-OCT) reconstructions of the optic nerve head from nonhuman primate (NHP) eyes. NCO was delineated within 40 radial, sagittal sections of 3-D histomorphometric reconstructions of 44 normal eyes of 38 NHPs, each perfusion fixed at IOP 10 mm Hg, and 3-D SD-OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany) volumes acquired in vivo from a separate group of 33 normal eyes of 24 NHPs. Within all reconstructions, a least-squares ellipse was fitted to the 80 NCO points. For each eye, the dimensions and plane error (a gauge of planarity) of the fitted ellipse were calculated. The NCO was successfully delineated within every section of each histomorphometric and SD-OCT reconstruction. Median plane error was similar within histomorphometric and SD-OCT volumes (8 microm, range 4-19, histomorphometry, and 10 microm, range 4-26, SD-OCT) and was small relative to the size of the ellipse. Median histomorphometric ellipse dimensions were 1453 mum (major axis, range 1218-1737) and 1066 microm (minor axis, range 808-1263). Median SD-OCT ellipse dimensions were 1512 microm (major axis, range 1191-1865) and 1060 microm (minor axis, range 772-1248). The NCO is biologically continuous and relatively planar within all 3-D histomorphometric and SD-OCT reconstructions. These characteristics support its further evaluation as a reference plane for cross-sectional and longitudinal measurement of optic nerve head structures using 3-D SD-OCT.


Xq25 duplications encompassing GRIA3 and STAG2 genes in two families convey recognizable X-linked intellectual disability with distinctive facial appearance.
We report here on two patients with Xq25 duplication encompassing GRIA3 gene, encoding glutamate receptor, ionotropic, AMPA subunit 3. The first case of Xq25 duplication was identified using genome-wide array comparative genomic hybridization (array-CGH) in a 24-year-old patient with syndromic intellectual disability. Based on similar facial features, we clinically suspected a second case of Xq25 duplication in a 4-year-old boy with intellectual disabilty. This duplication was confirmed by multiplex ligation-dependent probe amplification (MLPA) of the GRIA3 gene, as well as by fluorescence in situ hybridization (FISH) and further refined by array-CGH. We suggest that Xq25 duplication is responsible for a novel clinically recognizable X-linked intellectual disability. Finally, the review of so far published Xq25 duplications support, in addition to the role of GRIA3 gene, a potential contribution of the duplication of STAG2 (Stromal Antigen 2) gene coding for the subunit SA1 of the cohesin complex in the clinical phenotype.


The Relationship between Clinical Symptoms and Urine Culture in Adult Patients with Acute Epididymitis.
We evaluated adult patients with acute epididymitis to identify the frequency of actual sexual contacts and the causative organism, and compared clinical examinations, degrees of manifested symptoms, and radiological test results. We reviewed the medical records of 65 patients older than 18 years presenting with acute epididymitis who had been treated between 2002 and 2011. Scrotal ultrasonography, urinalysis, and urine culture were performed to diagnose the acute epididymitis. Patients were divided into negative (n=45) and positive (n=20) urine culture groups. Then the latter groups were subdivided into a sexually transmitted organism (STO) culture group (n=13) and a non-STO (n=7) culture group. Data on any history of sexual contact, scrotal pain and tenderness, symptoms of urethritis (discharge, dysuria, urethral burning, or irritation), and lower urinary tract symptoms (dysuria, frequency, and urgency of urination) were obtained from all of the subjects. Patients in the positive urine culture group were significantly younger than those in the other group (p=0.224) and were more likely to have a history of sexual contact at least two weeks prior to onset of epididymitis (p=0.012). They had also a significantly enlarged epididymal head and significantly more severe complaints of pain or tenderness than those of latter group (p=0.348, p=0.288). However, the difference in these measures between the STO and non-STO group was not significant, except in the case of age (p=0.044). Patients of the positive urine culture group with acute epididymitis were significantly younger and more sexually active than the others. They also had severe pain or tenderness and an enlarged epididymal head. There was a close association between clinical symptoms, a positive urine culture, and ultrasonographic findings.


Cyclic AMP signaling in bivalve molluscs: an overview.
The cyclic AMP (cAMP)-dependent signaling accounts for the control of cellular cascades involved in many physiological functions, and a wealth of information is available on the cAMP system that operates in mammalian cells. Nevertheless, cAMP has a central role also in nonmammalian vertebrates and invertebrates. The present review aims at examining the information available on bivalve molluscs, from the first studies carried out in the early 1980s to the last progresses made in the present days. The major focus is on the structural and operational characteristics of the main actors of the signaling pathway, i.e., adenylyl cyclase, G proteins, and protein kinase A, and on the role played by the cyclic nucleotide on smooth muscle, heart, gills, gonads, and metabolism regulation. Moreover, recent evidence regarding the cAMP system as a target of environmental stress factors are discussed. It will become clear that cAMP does play a wide and important role in bivalve physiology. Several issues have been sufficiently clarified, although investigated only in a few model species. However, further fundamental aspects remain unknown, mainly regarding molecular features and interactions with other signaling pathways, thus requiring further elucidation.


Killer cell immunoglobulin-like receptor expression delineates in situ Sézary syndrome lymphocytes.
p140/KIR3DL2 has been identified in malignant cell lines isolated from the skin and blood of patients with transformed mycosis fungoides (MF) and Sézary's syndrome (SS). For the first time, the expression of a cell membrane structure appeared to be able to distinguish CD4+ tumour lymphocytes from reactive lymphocytes in these small cutaneous T-cell lymphomas (CTCLs). This study has examined the in vivo expression of this receptor in various CTCL subtypes, which constituted a heterogeneous group. Tumour cells diffusely expressed KIR in SS, in lymphomatoid papulosis (LyP) and in CD4+CD30+ as well as CD8+ large cell pleomorphic CTCL. In contrast, the infiltrating lymphocytes did not express KIR in MF at the patch/plaque stage or in CD4+CD30- large cell pleomorphic CTCL, except for scattered small cells. One quarter of the transformed MF tested exhibited KIR+ tumour cells, suggesting heterogeneity in this subtype. KIR expression was also examined in inflammatory lesions characterized by a dense infiltrate of T cells, such as lupus erythematosus and lichen planus. Only scattered CD8+ cells in lichen planus expressed a significant amount of KIR3DL2. Taken together, these results show for the first time that KIR molecules are expressed in distinct subtypes of malignant CTCL. It is also shown for the first time that SS and MF, which are frequent variants of CTCL with similar histological features, can be distinguished by their KIR3DL2 expression analysis. The identification of this KIR also differentiates between lupus erythematosus and lichen planus, which are both diseases with dense benign lymphocytic infiltrates.


Virulence of a Bordetella pertussis strain expressing a mutant adenylyl cyclase with decreased calmodulin affinity.
Bordetella pertussis, the pathogen responsible for whooping cough, produces a toxic calmodulin-sensitive adenylyl cyclase which enters animal cells and increases intracellular cAMP. A point mutant of B. pertussis with abolished adenylyl cyclase catalytic activity was over 1000-fold less pathogenic to newborn mice than wild-type bacteria, demonstrating the importance of the adenylyl cyclase for B. pertussis virulence (Gross et al.). The B. pertussis adenylyl cyclase is highly sensitive to calmodulin with an apparent Kd for calmodulin of approximately 1 nM. The importance of this high-affinity calmodulin binding for virulence in vivo was examined by the creation of a B. pertussis point mutant (Trp-242 to Glu-242) with 200-fold lower calmodulin affinity than the native enzyme. This mutant B. pertussis strain retained its virulence in a newborn mouse model of pertussis, but the time course for establishment of a lethal infection in vivo was significantly delayed for the mutant strain. These data illustrate that high-affinity calmodulin binding is not obligatory for the activity of this toxin but is important for the rate for establishment of a lethal infection.


Co-articulatory variability and articulatory-acoustic correlations for consonants.
This paper is an investigation of articulatory-acoustic correlations differing in degree of articulatory constraint. Data on F2 and on dorsopalatal contact (electropalatographic, EPG) were collected for the sequences /iCi/ and /aC./ with seven Catalan consonants differing in place and manner of articulation (velarised /l/, /n/, /n/, /s/, /f/, /l/, /p/). These consonants are characterised by different degrees of tongue dorsum constraint depending on their production requirements (dorsals > non-dorsals, fricatives > non-fricatives, etc.). The results showed an inverse relationship between vowel-dependent coarticulation and the degree of consonant-dependent articulatory constraint. F2 and dorsopalatal contact size were found to be positively correlated across consonants and speakers, and across consonants for each individual speaker. Correlation values were much lower for each consonant across speakers. These findings are discussed in the light of the acoustic theory of speech production and possible clinical applications are suggested.


cGMP-dependent protein kinase in dorsal root ganglion: relationship with nitric oxide synthase and nociceptive neurons.
Nitric oxide and cGMP influence plasticity of nociceptive processing in spinal cord. However, effectors for cGMP have not been identified in sensory pathways. We now demonstrate that cGMP-dependent protein kinase I (cGKl) occurs in the DRGs at levels comparable to that in cerebellum, the richest source of cGKl in the body. Immunohistochemical studies reveal that cGKl is concentrated in a subpopulation of small- and medium-diameter DRG neurons that partially overlap with substance P and calcitonin gene-related polypeptide containing cells. During development, cGKl expression throughout the embryo is essentially restricted to sensory neurons and to the spinal floor and roof plates. Neuronal nitric oxide synthase (nNOS) is coexpressed with cGKl in sensory neurons during embryonic development and after peripheral nerve axotomy. The primary target for cGKl in cerebellum, G-substrate, is not present in developing, mature, or regenerating sensory neurons, indicating that other proteins serve as effectors for cGKl in sensory processing. These data establish sensory neurons as a primary locus for cGMP actions during development and suggest a role for cGKl in plasticity of nociception.


Assessment of locomotion in chlorine exposed mice by computer vision and neural networks.
Assessment of locomotion following exposure of animals to noxious or painful stimuli can offer significant insights into underlying mechanisms of injury and the effectiveness of various treatments. We developed a novel method to track the movement of mice in two dimensions using computer vision and neural network algorithms. By using this system we demonstrated that mice exposed to chlorine (Cl(2)) gas developed impaired locomotion and increased immobility for up to 9 h postexposure. Postexposure administration of buprenorphine, a common analgesic agent, increased locomotion and decreased immobility times in Cl(2)- but not air-exposed mice, most likely by decreasing Cl(2)-induced pain. This method can be adapted to assess the effectiveness of various therapies following exposure to a variety of chemical and behavioral noxious stimuli.


[Experimental and ultrastructural study of synapses in the substantia gelatinosa after electrical acupuncture].
Ultrastructural changes of synapses in the rat substantia gelationsa of the spinal caudal trigeminal nucleus were quantitatively examined following electrical acupuncture at "Sibai" for 30 minutes. Various structural changes were observed: Spherical synaptic vesicles were clustered toward the presynaptic membrane, the number of the vesicles tended to decrease, the width of the postsyiincreased and mitochondria were also increased in the bouton. These various types of synaptic alterations related to boutons are interpreted as the morphological changes induced by the acupuncture in the region corresponding to "Sibai".


Effects of the Atmosphere on the Propagation of 10.6-micro Laser Beams.
This paper gives an overview of the use of a wave optics computer code to model the propagation of high power CO(2) laser beams in the atmosphere. The nonlinear effects of atmospheric heating and kinetic cooling phenomena are included in the analysis. Only steady-state, nonturbulent cases are studied. Thermal conduction and free convection are assumed negligible compared to other effects included in the calculation. Results showing the important effect of water vapor concentration on beam quality are given. Beam slewing is also studied. Comparison is made with geometrical optics results, and good agreement is found with laboratory experiments that simulate atmospheric propagation.


FT-ICR mass spectrometry: Superconducting magnet, external ion source, ion-molecule reactions, and ion-ion traps.
The world of Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry has witnessed, especially in the last 30 years significant advances in many fields of science, such as electronics, magnets, new ICR cell designs, developed ICR event sequences, modern external ionization sources, and linear ion beam guides, as well as modern vacuum technology. In this review, a brief account is given focusing especially on the studies performed in Wanczek's group and ICR research laboratory at the University of Bremen. An FT-ICR mass spectrometer has been developed with a high magnetic field superconducting magnet, operating at 4.7 T. At this magnetic field, a trapping time of 13.5 h was obtained with 30% efficiency. For the tetrachloromethane molecular ion, m/z 166, a mass-resolving power m/Δm = 1.5 × 106 was measured at a pressure of 2 × 10-8 Torr. The transition from magnet sweep to frequency sweep and the application of Fourier-transform has greatly enhanced the ICR technology. External ion sources were invented and differential pumping schemes were developed for enabling ultrahigh vacuum condition for ICR detection, while guiding ions at relatively higher pressures, during their flight to the ICR cell. With the external ion source, a time-of-flight ICR tandem instrument is built. A method to measure the ion flight time and to trap the ions in the ICR cell is described. Many ICR cell characteristics such as z-axis ion ejection and coupling of radial and axial ion motions in a superposed homogeneous magnetic and inhomogeneous trapping electric field were extensively studied. Gas-phase ion-molecule reactions of several reactive inorganic compounds with a focus on phosphorous and sulfur as well as silicon chemistry were also studied in great detail. The gas-phase ion chemistry of several trifluoromethyl-reagents such as trifluoromethyltrimethylsilane and tris(trifluoromethyl)phosphine were also investigated in ICR. Dual polarities multisegmented ICR cells were invented and deeply characterized. Sophisticated ICR pulse event programs were developed to enable long-range ion-ion interactions between simultaneously trapped positive and negative ions.


DFRscore: Deep Learning-Based Scoring of Synthetic Complexity with Drug-Focused Retrosynthetic Analysis for High-Throughput Virtual Screening.
Recently emerging generative AI models enable us to produce a vast number of compounds for potential applications. While they can provide novel molecular structures, the synthetic feasibility of the generated molecules is often questioned. To address this issue, a few recent studies have attempted to use deep learning models to estimate the synthetic accessibility of many molecules rapidly. However, retrosynthetic analysis tools used to train the models rely on reaction templates automatically extracted from a large reaction database that are not domain-specific and may exhibit low chemical correctness. To overcome this limitation, we introduce DFRscore (Drug-Focused Retrosynthetic score), a deep learning-based approach for a more practical assessment of synthetic accessibility in drug discovery. The DFRscore model is trained exclusively on drug-focused reactions, providing a predicted number of minimally required synthetic steps for each compound. This approach enables practitioners to filter out compounds that do not meet their desired level of synthetic accessibility at an early stage of high-throughput virtual screening for accelerated drug discovery. The proposed strategy can be easily adapted to other domains by adjusting the synthesis planning setup of the reaction templates and starting materials.


Impaired anaplerosis and insulin secretion in insulinoma cells caused by small interfering RNA-mediated suppression of pyruvate carboxylase.
Anaplerosis, the synthesis of citric acid cycle intermediates, by pancreatic beta cell mitochondria has been proposed to be as important for insulin secretion as mitochondrial energy production. However, studies designed to lower the rate of anaplerosis in the beta cell have been inconclusive. To test the hypothesis that anaplerosis is important for insulin secretion, we lowered the activity of pyruvate carboxylase (PC), the major enzyme of anaplerosis in the beta cell. Stable transfection of short hairpin RNA was used to generate a number of INS-1 832/13-derived cell lines with various levels of PC enzyme activity that retained normal levels of control enzymes, insulin content, and glucose oxidation. Glucose-induced insulin release was decreased in proportion to the decrease in PC activity. Insulin release in response to pyruvate alone, 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) plus glutamine, or methyl succinate plus beta-hydroxybutyrate was also decreased in the PC knockdown cells. Consistent with a block at PC, the most PC-deficient cells showed a metabolic crossover point at PC with increased basal and/or glucose-stimulated pyruvate plus lactate and decreased malate and citrate. In addition, in BCH plus glutamine-stimulated PC knockdown cells, pyruvate plus lactate was increased, whereas citrate was severely decreased, and malate and aspartate were slightly decreased. The incorporation of 14C into lipid from [U-14C]glucose was decreased in the PC knockdown cells. The results confirm the central importance of PC and anaplerosis to generate metabolites from glucose that support insulin secretion and even suggest PC is important for insulin secretion stimulated by noncarbohydrate insulin secretagogues.


The Practical Potential of Bacilli and Their Enzymes for Industrial Production.
Bacillus spp. are an affordable source of enzymes due to their wide distribution, safety in work, ease of cultivation, and susceptibility to genetic transformations. Researchers are particularly interested in proteolytic enzymes, which constitute one of the most diverse groups of microbial proteins in terms of properties. Despite the long history of their research, this group of enzymes continue to show great potential for practical application in the biomedical industry, as well as in the agricultural industry. Thus, the unique properties of bacillary proteinases, such as stability in a wide range of temperatures and pH, high specificity, biodegradability of a wide range of substrates, and the high potential of sequenced Bacillus genomes are a powerful foundation for the development of new biotechnologies. The current review aims to discuss recent studies on various enzymes in particular, proteinases produced by bacteria of the genus Bacillus, along with their prospective practical applications. This article also presents an interpretive summary of the recent developments on the usage of probiotic Bacillus strains as potential feed additives.


Usage pattern of the complex masticatory muscles in the shingleback lizard, Trachydosaurus rugosus: A model for muscle placement.
This wide-ranging, omnivorous lizard of Australia has a very complex adductor muscle mass, with fibers differing in length by a factor of three and in insertion angle by 90 degrees. Stimulated muscles produce maximal moment with the mouth nearly fully open. The opening mechanism appears to involve only simple rotation and no translation of the mandible. EMGs indicate that the entire mass is activated equivalently in crushing and there are no temporal subdivisions, for instance, matching activity to angle of opening. During crushing of hard objects, the chin is brought into contact with the ground so that the subvertebral muscles may aid buccal closure. The lizards also activate the muscles in a pulsatile staircase effect leading to an unfused tetanus that generates forces several times the twitch level. Application in parallel of a maximum number of sarcomeres to the crushing bite appears to be the major design characteristic. Hence, this species offers an ideal case for analysis of the effects of different sarcomere placements on the simple movement generated. For the primary adductor muscles, the angles of fiber insertion relative to the lines connecting each insertion with the jaw joint are equivalent; this relation persists as the mouth opens. Also, fiber lenghts are proportional to the distance between jaw joint and site of insertion so that each sarcomere contributes equally to the movement generated. Complex tendons provide additional space for muscle placement. Some of these also extend beyond the bony attachment sites, producing tendinous "coronoid processes." The fibers of laterally and ventrally placed muscles are short relative to the length of the entire muscle, insert at relatively short moment arms, and undergo short excursion during opening; however, there are many such fibers. Also, muscles with a low incident angle are crossed; they apparently protect the jaw joint from horizontal (disarticulating) forces.


Comparison of the effects of acute and chronic administration of ketamine on hippocampal oscillations: relevance for the NMDA receptor hypofunction model of schizophrenia.
The proper organization and function of GABAergic interneuron networks is essential for many cognitive processes and abnormalities in these systems have been documented in schizophrenic patients. The memory function of the hippocampus depends on two major patterns of oscillations in the theta and gamma ranges, both requiring the intact functioning of the network of fast-firing interneurons expressing parvalbumin. We examined the ability of acute and chronic administration of NMDA receptor (NMDA-R) antagonists to recapitulate the oscillatory dysfunctions observed in schizophrenia. In freely moving rats, acute injection of MK801 or ketamine increased gamma power in both CA1 and dentate gyrus of the hippocampus. Theta peak shifted to higher frequencies whereas the average 5-10 Hz theta power decreased by 24% in CA1 and remained high in the dentate gyrus. Strong increase in CA1 gamma and decrease in theta power triggered by brainstem stimulation were found under urethane anesthesia. In contrast to acute experiments, chronic administration of ketamine caused a steady decline in both gamma and theta oscillations, 2-4 weeks after treatment. A further important difference between the two models was that the effects of acute injection were more robust than the changes after chronic treatment. Chronic administration of ketamine also leads to decrease in the number of detectable parvalbumin interneurons. Histological examination of interindividual differences indicated, however, that within the ketamine treated group a further decrease in parvalbumin neurons correlated with strengthening of oscillations. The findings are consistent with abnormalities of oscillations in human schizophrenia and further validate the NMDA-R hypofunction hypothesis.


Unravelling the Role of Rhizospheric Plant-Microbe Synergy in Phytoremediation: A Genomic Perspective.
Accretion of organic and inorganic contaminants in soil interferes in the food chain, thereby posing a serious threat to the ecosystem and adversely affecting crop productivity and human life. Both endophytic and rhizospheric microbial communities are responsible for the biodegradation of toxic organic compounds and have the capability to enhance the uptake of heavy metals by plants via phytoremediation approaches. The diverse set of metabolic genes encoding for the production of biosurfactants and biofilms, specific enzymes for degrading plant polymers, modification of cell surface hydrophobicity and various detoxification pathways for the organic pollutants, plays a significant role in bacterial driven bioremediation. Various genetic engineering approaches have been demonstrated to modulate the activity of specific microbial species in order to enhance their detoxification potential. Certain rhizospheric bacterial communities are genetically modified to produce specific enzymes that play a role in degrading toxic pollutants. Few studies suggest that the overexpression of extracellular enzymes secreted by plant, fungi or rhizospheric microbes can improve the degradation of specific organic pollutants in the soil. Plants and microbes dwell synergistically, where microbes draw benefit by nutrient acquisition from root exudates whereas they assist in plant growth and survival by producing certain plant growth promoting metabolites, nitrogen fixation, phosphate solubilization, auxin production, siderophore production, and inhibition or suppression of plant pathogens. Thus, the plant-microbe interaction establishes the foundation of the soil nutrient cycle as well as decreases soil toxicity by the removal of harmful pollutants. The perspective of integrating genetic approach with bioremediation is crucial to evaluate connexions among microbial communities, plant communities and ecosystem processes with a focus on improving phytoremediation of contaminated sites.


Oligomerization of DNMT3A controls the mechanism of de novo DNA methylation.
DNMT3A is one of two human de novo DNA methyltransferases essential for regulating gene expression through cellular development and differentiation. Here we describe the consequences of single amino acid mutations, including those implicated in the development of acute myeloid leukemia (AML) and myelodysplastic syndromes, at the DNMT3A·DNMT3A homotetramer and DNMT3A·DNMT3L heterotetramer interfaces. A model for the DNMT3A homotetramer was developed via computational interface scanning and tested using light scattering and electrophoretic mobility shift assays. Distinct oligomeric states were functionally characterized using fluorescence anisotropy and steady-state kinetics. Replacement of residues that result in DNMT3A dimers, including those identified in AML patients, show minor changes in methylation activity but lose the capacity for processive catalysis on multisite DNA substrates, unlike the highly processive wild-type enzyme. Our results are consistent with the bimodal distribution of DNA methylation in vivo and the loss of clustered methylation in AML patients. Tetramerization with the known interacting partner DNMT3L rescues processive catalysis, demonstrating that protein binding at the DNMT3A tetramer interface can modulate methylation patterning. Our results provide a structural mechanism for the regulation of DNMT3A activity and epigenetic imprinting.


Bispectral Index compared to Ramsay score for sedation monitoring in intensive care units.
Continuous monitoring is of paramount importance in order to obtain a correct level of sedation in ICU patients. Clinical scoring systems, although simple and inexpensive, are often inadequate in evaluating the patient level of consciousness. Among instrumental tools for sedation monitoring, Bispectral Index (BIS) is now widely used due to its reliability and applicability. Nevertheless some doubts still exist regarding its usefulness in ICU. Sedation, obtained with propofol or midazolam, was monitored with Ramsay scale and BIS in 40 patients admitted in ICU for postoperative monitoring after major abdominal or vascular surgery. A correlation between Ramsay score and BIS values was searched using Pearson test. A good correlation between Ramsay score and BIS values was observed. At the deeper levels of sedation a wide range of BIS values corresponds to Ramsay score 6, indicating various levels of central nervous system depression that are not identified by clinical evaluation. BIS monitoring is useful in ICU patients and allows a finest differentiation of sedation level in deeply sedated ICU patients.


Trans-synaptic interactions of ionotropic glutamate receptors.
Trans-synaptic interactions organize the multiple steps of synaptic development and are critical to generate fully functional neuronal circuits. While trans-synaptic interactions are primarily mediated by cell adhesion molecules (CAMs), some directly involve ionotropic glutamate receptors (iGluRs). Here, we review the expanding extracellular and trans-synaptic proteome of iGluRs. We discuss the role of these molecular networks in specifying the formation of excitatory and inhibitory circuits and in the input-specific recruitment of iGluRs at synapses in various cell types and brain regions. We also shed light on human-specific mutations affecting iGluR-mediated trans-synaptic interactions that may provide unique features to the human brain and contribute to its susceptibility to neurodevelopmental disorders. Together, these data support a view in which iGluR function goes far beyond fast excitatory synaptic transmission by shaping the wiring and the functional properties of neural circuits.


Platelet Count, Mean Platelet Volume, and Red Cell Distribution Width as Markers for Psoriasis Severity.
Psoriasis is a chronic, inflammatory skin condition that is growing in prevalence globally. Routinely available options to assess psoriasis severity and progression are limited. More options are needed to monitor disease progression as therapeutic management is based on disease severity. This study evaluates the usage of complete blood count components (CBC) including platelet count, mean platelet volume (MPV), and red cell distribution width (RDW) as hematological markers for assessing psoriasis severity. In this cross-sectional study of 120 patients with psoriasis, disease severity was assessed using the PASI score followed by a blood draw to determine whether correlations existed between each marker and PASI score. A significant, positive correlation was found between total platelet count and PASI while no such correlation was found in MPV and RDW. When stratifying for age, duration of disease, sex, and body parts involved, we found intriguing relationships and offer potential explanations for their occurrence. Our findings suggest that hematological parameters MPV, platelet count, and RDW found in the CBC are useful in identifying psoriasis severity to some extent. We foresee the use of RDW, MPV, and platelet count biomarkers as a complement to the PASI score in assessing severity for psoriasis patients, while also as a gauge for likelihood of developing comorbidities such as cardiovascular disease. J Drugs Dermatol. 2022;21(2):156-161. doi:10.36849/JDD.6127.


Rh antigen and phenotype frequencies and probable genotypes for the four main ethnic groups in Port Harcourt, Nigeria.
Rh is the most complex and polymorphic of the RBC group systems and is of major importance in transfusion medicine. Data are not available on the frequency of Rh antigens D, C, E, c, and e in Port Harcourt, Nigeria. Two mL of venous blood was collected into an EDTA tube from each of 400 persons of mixed ethnic groups recruited for the study. The study population comprised 167 Ijaws (41.8%), 141 Ikwerres (35.2%), 50 Ekpeyes (12.5%), and 42 Ogonis (10.5%). The RBCs were phenotyped for D, C, E, c, and e antigens according to standard serologic methods. The most frequently occurring antigen was found to be c (99.8%),followed by e (98.7%), then D (95.0%), E (20.5%), and finally C (17.7%). The antigens occurred independently of the ethnic groups (p > 0.05) except the antithetical antigens Ee, which were found to be statistically significant in the Ijaw ethnic group when subjected to Pearson chi-square test (chi(2) = 9.890, p < 0.02). One (0.2%) of the study population was found to be c- while 20 (5.0%) were D-.


De novo transcriptome sequencing analysis and comparison of differentially expressed genes (DEGs) in Macrobrachium rosenbergii in China.
Giant freshwater prawn (GFP; Macrobrachium rosenbergii) is an exotic species that was introduced into China in 1976 and thereafter it became a major species in freshwater aquaculture. However the gene discovery in this species has been limited to small-scale data collection in China. We used the next generation sequencing technology for the experiment; the transcriptome was sequenced of samples of hepatopancreas organ in individuals from 4 GFP groups (A1, A2, B1 and B2). De novo transcriptome sequencing generated 66,953 isogenes. Using BLASTX to search the Non-redundant (NR), Search Tool for the Retrieval of Interacting Genes (STRING), and Kyoto Encyclopedia of Genes and Genome (KEGG) databases; 21,224 unigenes were annotated, 9,552 matched unigenes with the Gene Ontology (GO) classification; 5,782 matched unigenes in 25 categories of Clusters of Orthologous Groups of proteins (COG) and 20,859 unigenes were consequently assigned to 312 KEGG pathways. Between the A and B groups 147 differentially expressed genes (DEGs) were identified; between the A1 and A2 groups 6,860 DEGs were identified and between the B1 and B2 groups 5,229 DEGs were identified. After enrichment, the A and B groups identified 38 DEGs, but none of them were significantly enriched. The A1 and A2 groups identified 21,856 DEGs in three main categories based on functional groups: biological process, cellular_component and molecular function and the KEGG pathway defined 2,459 genes had a KEGG Ortholog-ID (KO-ID) and could be categorized into 251 pathways, of those, 9 pathways were significantly enriched. The B1 and B2 groups identified 5,940 DEGs in three main categories based on functional groups: biological process, cellular_component and molecular function, and the KEGG pathway defined 1,543 genes had a KO-ID and could be categorized into 240 pathways, of those, 2 pathways were significantly enriched. We investigated 99 queries (GO) which related to growth of GFP in 4 groups. After enrichment we identified 23 DEGs and 1 KEGG PATHWAY 'ko04711' relation with GFP growth.


Application of the anatomical method to estimate the maximum adult stature and the age-at-death stature.
This study focuses on the age adjustment of statures estimated with the anatomical method. The research material includes 127 individuals from the Terry Collection. The cadaveric stature (CSTA)-skeletal height (SKH) ratios indicate that stature loss with age commences before SKH reduction. Testing three equations to estimate CSTA at the age at death and CSTA corrected to maximum stature from SKH indicates that the age correction of stature should reflect the pattern of age-related stature loss to minimize estimation error. An equation that includes a continuous and linear age correction through the entire adult age range [Eq. (1)] results in curvilinear stature estimation error. This curvilinear stature estimation error can be largely avoided by applying a second linear equation [Eq. (2)] to only individuals older than 40 years. Our third equation [Eq. (3)], based on younger individuals who have not lost stature, can be used to estimate maximum stature. This equation can also be applied to individuals of unknown or highly uncertain age, because it provides reasonably accurate estimates until about 60/70 years at least for males.


Phase shift of coupled oscillator model with feedbacks in response to multiple bright light exposure.
Human temperature rhythm was reported to have type 0 phase response curve (PRC) to multiple bright light exposure; however, mechanisms underlying this finding could not be clarified easily in a theoretical framework, and has not yet been confirmed by other researchers. In this paper, under reproduced photic exposure, phase response properties of a coupled three oscillator model were investigated to identify the possible mechanism underlying the experimental finding. The resulting phase shift of an oscillator reached approximately 12 h, and changed its sign acutely at the cross-over point of an original PRC of the oscillator. This type 0-like phase shift was produced by an accumulated phase response during the oscillator's re-entrainment process to the photic exposure. The organization of coupled oscillators affected the total amount of this phase shift.


Accuracy of measured vancomycin serum concentrations in patients with end-stage renal disease.
To review information related to the accuracy of vancomycin serum drug concentrations in patients with end-stage renal disease, focusing on available assays and mechanisms of cross-reactivity. Primary and review articles identified from a MEDLINE search (January 1980-June 1999) and through secondary sources. All articles identified were evaluated, and all relevant information was included in this review. Falsely elevated vancomycin serum concentrations may occur in patients with renal dysfunction. The underlying mechanism is due to the formation and accumulation of a pseudo-metabolite, the vancomycin crystalline degradation product (CDP). Vancomycin is converted to CDP when exposed to heat, including normal body temperature. Because the molecular structures of CDP and vancomycin are similar, both molecules are detected by polyclonal immunoassay systems used in clinical laboratories. This cross-reactivity leads to falsely elevated serum vancomycin concentrations in excess of 50-70%. Such large assay inaccuracies may result in improper dosage adjustments and therapeutic failures. A monoclonal immunoassay system has been developed that does not significantly cross-react with CDP. To appropriately interpret laboratory results, it is essential for clinicians to be aware of the vancomycin-CDP cross-reactivity problem and to be familiar with the specific assay used to measure vancomycin concentrations in patients with renal dysfunction.


Chronic Obstructive Pulmonary Disease and Dysphagia: A Synergistic Review.
Chronic obstructive pulmonary disease (COPD) is a leading global cause of death and disability. The literature has previously established clear physiological characteristics of COPD-related dysphagia (swallowing difficulties). However, COPD and dysphagia are both also intimately tied to breathing and contribute to a cascade of secondary physio-psycho-emotional sequalae, such as COPD exacerbation, anxiety, depression, increased economic burden, social isolation, and decreased quality of life. Further, the collective impact of these comorbidities may magnify disease impact, resulting in a downward spiral of well-being. Thus, the clinical relevance of COPD's and dysphagia's frequently occurring and overlapping sequelae cannot be overlooked, as the disease-related burden of both disorders is deeply rooted in the presence of concomitant physiological and psycho-emotional consequences. The current review explores the complex network of interactions between COPD, dysphagia, and their outcomes, framing this relationship within a mind-body-breath framework. Ultimately, we propose a model that more comprehensively captures the constellation of interrelated disease characteristics and consequences, highlighting a need for researchers and healthcare providers to consider disease impact more broadly in order to maximize treatment outcomes.


Bone scanning in assessing viability of vascularized skeletal tissue transplants.
One hundred and eight bone scans using 99mTechnetium methylene diphosphonate (MDP) were performed in rats undergoing vascularized and nonvascularized syngeneic and allogeneic transplants of the hind limb, and in control animals. A six-level system of grading the radionuclide uptake in the graft was used to evaluate healing or complications of the transplantation. Bone scanning was superior to other modalities in assessing viability of the graft. Bone scans were able to: (1) immediately confirm vascular patency, thus obviating angiography; (2) demonstrate differences in the rate of repair in syngeneic and allogeneic nonvascularized grafts; (3) sequentially assess vascularized allograft rejection; and (4) document long-term effects, such as bone atrophy due to disuse and early epiphyseal maturity.


Prototype Michelson interferometer with Fabry-Perot cavities.
We describe a rigid, internally modulated Michelson interferometer with Fabry-Perot cavities in the interferometer arms. The high contrast (0.986) and the small cavity losses (2.7%) permit efficient use of the light power available. The measured shot-noise-limited displacement sensitivity for 35mW of light power is 2.5 x 10(-17) m radicalHz, in good agreement with the calculated signal-to-noise ratio.


Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus.
Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have recently been investigated as two new inflammatory markers used in the assessment of systemic inflammation in many diseases. The purpose of the study was to investigate their relation with disease activity in newly diagnosed SLE patients. The study population consisted of 116 SLE patients who did not receive any treatment and 136 healthy controls. We divided the patients into two groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K) system. Group 1 included patients with a score of 9 and lower (patients with mild disease activity), and Group 2 included patients with a score of >9 (patients with severe disease activity). Correlations between NLR, PLR and disease activity were analyzed. The NLR and PLR of SLE patients were significantly higher compared to those of the controls (both P<0.001). There was a statistically significant difference in NLR and PLR between Group 1 and Group 2 (both P<0.05). SLEDAI scores positively correlated with NLR (r=0.312, P<0.001) and PLR (r=0.298, P<0.001). Furthermore, SLE patients with nephritis had higher NLR levels than those without nephritis (P=0.027). Based on the ROC curve, the best NLR cut-off value to predict SLE patients with severe disease activity was 2.26, with 75% sensitivity and 50% specificity, whereas the best PLR cut-off value was 203.85, with 42.3% sensitivity and 83.9% specificity. NLR and PLR were two useful inflammatory markers for assessment of disease activity in patients with SLE.


Improvement of the safety systems in cell separators. The new safety concept for the cell separator AS 104 (Fresenius).
The new, extended safety requirements for cell separators call for a new generation of machines to address current safety needs. In order to ensure safe treatment, the complete safety concept is of decisive importance - this includes closed seal-less systems, continuous operation, fractions collected externally to the centrifuge, and pump tubings, connections and clamps which are color and direction coded. 'Human failure' as a cause of fault should be excluded for these highly technical appliances - for example, through the use of 'fail-safe' circuits, drip-controlled ACD flow by a separate adjustable pump, detection of damages to blood components by hemolysis control.


Rural dentistry--lessons from other countries.
For people living in rural and remote areas, unmet dental care remains one of the most urgent healthcare needs. Persons living in rural areas are likely to be poorer, older, less health literate, use drinking water that is not fluoridated, have more caries, fewer teeth, and less money to spend on dental care than persons living in urban areas. It is impossible to meet all of the unmet needs of this rural population. Therefore, prevention must be the focus of any program and some of these programs developed by other countries may be useful for the rural U.S.


The association between coracoacromial ligament morphology and rotator cuff tears: A cadaveric study.
To determine the association between coracoacromial ligament (CAL) morphology and rotator cuff tears. The present study is a prospective cohort study based on the dissection of 172 shoulders from 86 (46 female, 40 male) formalin embalmed European Caucasian cadavers, with a median age of 82 years. The anatomy of CAL was examined, including its morphology and parametric measurements, while the rotator cuff tendons were inspected for the presence of tears. Gross examination of the CAL in 155 shoulders revealed a variable number of bands as follows: 28 (18%) had one band, 56 (36%) two bands and 71 (46%) three or more bands. Inspection of the rotator cuff tendons showed the presence of tears in 77 (50%) shoulders, of which 37 (24%) were partial and 40 (26%) were full-thickness tears. Statistical analysis showed a significant association (P < 0.05) between CAL band number and the prevalence of a rotator cuff tear. A high proportion of rotator cuff tears were observed in shoulders with two (52%) and three or more CAL bands (56%) compared to single band ligaments (29%). Parametric assessment of the CAL in shoulders with rotator cuff tears showed significantly greater (P < 0.05) attachment widths and ratios, thicker ligament bands, and larger cross-sectional areas compared to the control group. Coracoacromial ligaments with more than a single band have a strong association with rotator cuff tears.


Improving the health of older people: what do we do?
This article, based on a paper given at the International Network for Studies Concerning Older Adults conference in Brazil, considers the health of older people. It argues that greater efforts must be made both to improve preventive healthcare interventions and enhance quality of life. It is suggested that nurses have a significant but, as yet, largely unrealized role to play and that action is needed if older people are to get maximum benefit from health care.


Gastric cancer: basic aspects.
Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. In the last years, molecular oncobiology studies brought to light a number of genes that are implicated in gastric carcinogenesis. This review is intended to focus on the recently described basic aspects that play key roles in the process of gastric carcinogenesis. Genetic variants of the genes IL-10, IL-17, MUC1, MUC6, DNMT3B, SMAD4, and SERPINE1 have been reported to modify the risk of developing GC. Several genes have been newly associated with gastric carcinogenesis, both through oncogenic activation (GSK3β, CD133, DSC2, P-Cadherin, CDH17, CD168, CD44, metalloproteinases MMP7 and MMP11, and a subset of miRNAs) and through tumor suppressor gene inactivation mechanisms (TFF1, PDX1, BCL2L10, XRCC, psiTPTE-HERV, HAI-2, GRIK2, and RUNX3). It also addressed the role of the inflammatory mediator cyclooxygenase-2 (COX-2) in the process of gastric carcinogenesis and its importance as a potential molecular target for therapy.


Integrative neuroimmunology of the digestive tract.
The epithelium of the gastrointestinal tract is continuously exposed to the external environment containing food antigens, microbes and other pathogens. Immunologic and nonimmunologic mechanisms contribute to the neutralization and elimination of these foreign antigens. The immune system of the intestine is the most extensive in the organism and involves diffuse populations of immune cells, lymphoid aggregates and intraepithelial lymphocytes. On the other hand, the functions of the digestive tract contribute to the overall host defense (mucus secretion, gastric acid secretion, water and electrolyte secretion and peristaltism). These functions are regulated by intrinsic and extrinsic nervous systems. It is currently recognized that the physiological and pathological responses of the intestine require an integrate neuroimmune network. Such neuroimmune regulation is based on anatomical and biochemical supports. Indeed, there are membrane-to-membrane contacts between axonal varicosities and the immune cells. Specific receptors for neurotransmitters such as substance P, vasoactive intestinal polypeptide and somatostatin have been identified in many immune cells. Nerve profile change has been described under pathological conditions such as parasitic infections and acute phase of inflammation. In addition to supporting the growth and survival of several populations of nerves the classical nerve growth factor (NGF) has been shown to affect an immune cell population by inducing mast cell hyperplasia. Furthermore the NGF can induce mast cell degranulation, acting directly on mast cell membrane NGF receptors or indirectly by NGF-mediated release of substance P by peripheral extrinsic or intrinsic nerves. Moreover, non-immune cells such as epithelial and smooth muscle cells can produce immunologic messengers under pathological conditions such as infectious diseases or inflammation. Besides the local regulation of gut functions, neuroimmune control can be exerted at extra-intestinal sites. During physiological and pathological conditions, gastrointestinal secretions and motor events are strongly regulated by the central nervous system. Moreover, infectious agents can induce cytokine and particularly interleukin-1 release by the brain astrocytes and microglial cells which have been shown to play a pivotal role in fever induction and modifications of the gastrointestinal functions. Visceral afferent fibers play a pivotal role in 'cross-communication' between central sites and immune response. Recent studies evoke, more specifically, the role of vagus as a key modulatory participant in the close relationship between the extraintestinal nerves and the immune system. Future work in this field will clarify the role of the different participants in the intimate communication between the gastrointestinal tract, immune system and central nervous system.


A protein-polymer hybrid mediated by DNA.
Protein-polymer hybrids (PPHs) represent an important and rapidly expanding class of biomaterials. Typically in these hybrids the linkage between the protein and the polymer is covalent. Here we describe a straightforward approach to a noncovalent PPH that is mediated by DNA. Although noncovalent, the DNA-mediated approach affords the highly specific pairing and assembly properties of DNA. To obtain the protein-DNA conjugate for assembly of the PPH, we report here the first direct copper catalyzed azide-alkyne cycloaddition-based protein-DNA conjugation. This significantly simplifies access to protein-DNA conjugates. The protein-DNA conjugate and partner polymer-DNA conjugate are readily assembled through annealing of the cDNA strands to obtain the PPH, the assembly of which was confirmed via dynamic light scattering and fluorescence spectroscopy.


Pattern formation of ion channels with state-dependent charges and diffusion constants in fluid membranes.
A model of mobile, charged ion channels in a fluid membrane is studied. The channels may switch between an open and a closed state according to a simple two-state kinetics with constant rates. The effective electrophoretic charge and the diffusion constant of the channels may be different in the closed and in the open state. The system is modeled by densities of channel species, obeying simple equations of electrodiffusion. The lateral transmembrane voltage profile is determined from a cable-type equation. Bifurcations from the homogeneous, stationary state appear as hard-mode, soft-mode, or hard-mode oscillatory transitions within physiologically reasonable ranges of model parameters. We study the dynamics beyond linear stability analysis and derive nonlinear evolution equations near the transitions to stationary patterns.


[Biomechanical study on effects of bone mineral density on fixation strength of expansive pedicle screw].
To evaluate the fixation strength of expansive pedicle screw (EPS) at different bone mineral density (BMD) levels, further to provide theoretical evidence for the clinical application of the EPS in patients with osteoporosis. Fresh human cadaver spines (T12-L5 spines) were divided into 4 levels: normal BMD, osteopenia, osteoporosis, and severe osteoporosis according to the value of BMD, 12 vertebra in each level. Conventional pedicle screw (CPS) or EPS was implanted into the bilateral vertebra in CPS group and EPS group, respectively, 12 screws in each group per BMD level. Screw pullout tests were conducted. The maximum pullout strength, stiffness, and energy absorption were determined by an AG-IS material testing machine with constant rate of loading in a speed of 5 mm/min. With the decline of BMD from normal to severe osteoporosis level, the maximum pullout strength and the stiffness correspondingly declined (P < 0.05). In CPS group, the energy absorption gradually decreased (P < 0.05); in EPS group, significant difference was found between other different BMD levels (P < 0.05) except between normal BMD and osteopenia and between osteoporosis and severe osteoporosis (P > 0.05). At the same BMD level, the maximum pullout strength of EPS group was significantly larger than that of CPS group (P < 0.05); the stiffness of EPS group was significantly higher than that of CPS group (P < 0.05) except one at normal BMD level; and no significant difference was found in the energy absorption between 2 groups (P > 0.05) except one at osteopenia level. No significant difference was found in maximum pullout strength, stiffness, and energy absorption between EPS group at osteoporosis level and CPS group at osteopenia level (P > 0.05); however, the maximum pullout strength, stiffness, and energy absorption of EPS group at severe osteoporosis level were significantly lower than those of CPS group at osteopenia level (P < 0.05). Compared with CPS, the EPS can significantly improve the fixation strength, especially in patients with osteopenia or osteoporosis.


Fistulization in a locally advanced case of squamous cell carcinoma of the prostate.
Squamous cell carcinoma of the prostate gland is very rare, constituting 0.5%-1% of all prostatic malignancies. Though it has a similar clinical presentation to prostate cancer, the tumor is more aggressive, spreading to bone, liver and lung. The median survival time is approximately 14 months. Diagnosis is exclusively by histology. Therapeutic options may include radical surgery, radiotherapy, chemotherapy, hormonal therapy or a combination of these treatments. We present a case of locally advanced squamous cell carcinoma of the prostate and comment on its management and subsequent disease related complication.


Activation of the Ir-N(pyridine) Bond in Half-Sandwich Tethered Iridium(III) Complexes.
We present four new organometallic half-sandwich iridium(III) complexes of formula [Ir(η5:κ1-C5Me4CH2py)(N,N)](PF6)2, bearing a N,N-chelating ligand [ethylenediamine (en), 1; 1,3-diaminopropane (dap), 2; 2,2'-bipyridine (bipy), 3; 1,10-phenanthroline (phen), 4]; and a derivatized cyclopentadienyl ligand, C5Me4CH2C5H4N, which forms an additional five-membered chelate. The latter is hemilabile, and the Ir-N(py) bond can be reversibly cleaved by various stimuli. The four complexes are unreactive toward hydrolysis at pH 7. Interestingly, 1 and 2 react with hydrochloric acid and formate, and speciation between closed and open tether complexes can be followed by 1H NMR spectroscopy. Complex 1 binds to nucleobase guanine (9-ethylguanine, 9-EtG), yet interaction to calf-thymus DNA was not observed. New X-ray structures of closed tether complexes 1-4 and open tether complexes [Ir(η5-C5Me4CH2pyH)(en)Cl](PF6)2 (1·HCl) and [Ir(η5-C5Me4CH2py)(en)H]PF6 (1·hyd) have been determined. Hydride capture is efficient for 1 and 2. The kinetics of Ir-H bond formation and hydride transfer in a model organic molecule have been investigated, revealing a strong dependence on the temperature. Coincubation of complex 1 with nontoxic concentrations of sodium formate decreases the IC50 value in MCF7 breast cancer cells, indicating the possibility of intracellular activation of the Ir-N(py) tether bond to generate cytotoxic activity via iridium-mediated transfer hydrogenation.


A reexamination of the role of clusterin as a complement regulator.
Clusterin is a highly conserved glycoprotein which has been proposed to protect host cells against complement-mediated cytolysis. We tested the hypothesis that clusterin is a complement regulator using erythrocytes and cells which had been stably transfected with a membrane-anchored form of clusterin as targets for complement-mediated cytolysis. Clusterin gave dose-dependent protection of antibody-coated sheep erythrocytes against complement-mediated lysis by diluted normal human serum. There was a linear relationship between the concentration of clusterin giving 50% protection and the concentration of serum; extrapolation of this to the case of undiluted human serum showed that a clusterin concentration at least two orders of magnitude greater than its physiological plasma concentration would be needed to confer protection against complement-mediated cytolysis under physiological conditions. Physiological concentrations of clusterin did not protect rabbit erythrocytes against alternative complement pathway-mediated lysis using dilute human serum. Exogenous clusterin had no effect on lysis of human erythrocytes triggered by the addition of inulin to autologous human serum. Induction of cell-surface clusterin expression by L929 (murine fibroblast) cells which had been stably transfected with cDNA for human clusterin linked to DNA coding for the 44 C-terminal amino acid residues of CD55 did not protect the cells against complement-mediated lysis by either normal or clusterin-depleted human serum. These data suggest that clusterin may not be a physiologically relevant regulator of complement activation.


Immunization of macaques with live simian human immunodeficiency virus (SHIV) vaccines conferred protection against AIDS induced by homologous and heterologous SHIVs and simian immunodeficiency virus.
To evaluate the vaccine potential of SHIVs attenuated by deletion of viral accessory genes, seven rhesus macaques were sequentially immunized with Delta vpu Delta nefSHIV-4 (vaccine-I) followed by Delta vpuSHIV(PPC) (vaccine-II). Despite the absence of virological evidence of productive infection with the vaccine strains, based on analysis of infectivity among peripheral blood mononuclear cells (PBMC) of the vaccinated animals, all seven animals developed binding as well as neutralizing antibodies against both vaccine-I and -II. The animals also developed vaccine virus-specific CTLs that recognized homologous as well as heterologous pathogenic SHIVs and SIV, and also soluble inhibitory factors that blocked the in vitro replication of the vaccine strains and different challenge viruses. Virus-specific cellular and humoral responses were sustained throughout a 58-week prechallenge period. To model aspects of natural transmission, the animals received a mucosal (rectal) challenge, with a mixture of three challenge viruses, SHIV(KU), SHIV(89.6)P, and SIV(mac)R71/17E. Two mock-vaccinated control animals inoculated with the same mixture of challenge viruses developed large numbers of infectious PBMC, high plasma viremia, and precipitous loss of CD4(+) T cells. The control animals did not develop any immune responses and succumbed to AIDS between 6 and 7 weeks postchallenge. All seven vaccinated animals became infected with challenge viruses as indicated by the presence of infectious cells in the PBMC and/or viral RNA in plasma. However, peak plasma viremia in vaccinates was two to nearly five logs lower than in the control animals and later plasma viral RNA became undetectable in all vaccinates. Vaccinated animals maintained normal CD4(+) T cell levels throughout the study. Challenge with pathogenic viruses caused massive anamnestic responses as determined by quantitation of virus-specific CD4(+) and CD8(+) T cells by intracellular IFN-gamma staining, and these cells persisted for at least 74 weeks. The study is still in progress and at this time DNA of SIV has become undetectable in lymph nodes of six of the seven vaccinates, SHIV(89.6)P in five of the seven, and SHIV(KU) in three of the seven animals.


Sleep-wake states change the interictal localization of candidate epileptic source generators.
To compare estimated epileptic source localizations from 5 sleep-wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3. Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2 and 5 SWS, and discordance as those unique to 1 SWS against 1-4 other SWS. 563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p = .0091). All five SWS contributed about 45% of their localizations to converge onto 17.0 ± 15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p = .0006) and most discordant (39.3% vs. 29.6%, p = .0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p = .0059). REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an "omni-concordant core" of source localizations shared by all five SWS is surrounded by a "penumbra" of source localizations shared by some but not all SWS. Uniquely, REM spares this core to "move" source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities.


AACR-NCI-EORTC--21st International Symposium. Molecular targets and cancer therapeutics--Part 2.
The 21st international symposium of the American Association for Cancer Research (AACR), the NCI and the European Organization for Research and Treatment of Cancer (EORTC), held in Boston, included topics covering the development of therapeutics and molecular targets in the field of cancer research. This conference report highlights selected presentations on the development of novel drugs for cancer. Investigational drugs discussed include RO-506876 (F Hoffmann-La Roche Ltd), GDC-0980 (Genentech Inc), EMD-1214063 and EMD-1204831 (Merck Serono SA), AR-mTOR01 and AR-mTOR-26 (Array BioPharma Inc), GSK-2126458 (GlaxoSmithKline plc), EXEL-1415 and EXEL-2008 (Exelixis Inc), FP-1039 (FivePrime Therapeutics Inc), and AV-412 (AVEO Pharmaceuticals Inc).


Hardship financing of out-of-pocket payments in the context of free healthcare in Zambia.
Despite the removal of user fees on public primary healthcare in Zambia, prior studies suggest that out-of-pocket payments are still significant. However, we have little understanding of the extent to which out-of-pocket payments lead patients to hardship methods of financing out-of-pocket costs. This study analyses the prevalence and determinants of hardship financing arising from out-of-pocket payments in healthcare, using data from a nationally-representative household health expenditure survey conducted in 2014. We employ a sequential logistic regression model to examine the factors associated with the risk of hardship financing conditional on reporting an illness and an out-of-pocket expenditure. The results show that up to 11% of households who reported an illness had borrowed money, or sold items or asked a friend for help, or displaced other household consumption in order to pay for health care. The risk of hardship financing was higher among the poorest households, female headed-households and households who reside further from health facilities. Improvements in physical access and quality of public health services have the potential to reduce the incidence of hardship financing especially among the poorest.


Separation Procedure and Partial Characterization of Two NAD(P)H Dehydrogenases from Cauliflower Mitochondria.
A procedure was developed to separate and partially purify two NAD(P)H dehydrogenases from the inner membrane of cauliflower (Brassica oleracea L.) mitochondria. The procedure used Triton X-100 extraction followed by (NH(4))(2)SO(4) precipitation and gel filtration (Sepharose G-200 column) chromatography. The first dehydrogenase fraction (which eluted in the column void volume) was specific for NADH, was stimulated by KCl addition, and was inhibited by acidic pH, sulfhydryl reagents, and elevated temperature. This fraction contained two major polypeptides with molecular weights of about 57,600 and 32,600 daltons. The fraction exhibited electron paramagnetic resonance (EPR) signals associated with a reduced (ferredoxin-type) iron-sulfur center.A second dehydrogenase fraction was eluted from the column after removal of the first dehydrogenase. This fraction oxidized NADH and NADPH, was stable at high temperatures, and had a broad pH optima that ranged from 6.0 to 7.8. Although it was relatively insensitive to additions of monovalent and divalent cations, its activity was sensitive to incubation with sulfhydryl reagents. The second dehydrogenase fraction contained five major polypeptides and lacked the iron-sulfur protein EPR signals shown by the first dehydrogenase fraction.The dehydrogenase fractions represent three potential sites of entry to mitochondrial electron transport; two sites for NADH and a third site for NADPH.


Zinc supplementation for four months does not affect growth in young north Indian children.
Our objective in this trial was to assess the impact of daily zinc supplementation on growth in young children. A double-blind, randomized, placebo-controlled trial was conducted in New Delhi, India. We enrolled 2482 children aged 6-30 mo who were supplemented daily with placebo or zinc (10 mg elemental zinc to infants and 20 mg to older children) for 4 mo. At enrollment, all children also received a single dose of vitamin A (104.7 micromol for infants and 209.4 micromol for older children). Weight and length were measured at enrollment and 4 mo later. Weekly visits were conducted by field workers to ascertain morbidity in the previous 7 d. Change in length, weight, length-for-age Z-scores (LAZ), and weight-for-length Z-scores (WLZ) after 4 mo of supplementation were assessed in the zinc and placebo groups. After 4 mo of supplementation, the weight and length gains in the 2 groups did not differ and there was no impact on LAZ, weight-for-age, and WLZ in the 2 groups. There was no substantial effect in any of the subgroups defined for age, income, gender, zinc levels in the crude analysis nor after adjusting for age, gender, income, breast-feeding status, and baseline anthropometric status. Despite successful zinc supplementation reflected in increased plasma zinc concentration and a substantially reduced incidence of diarrhea and pneumonia in zinc-supplemented children, the intervention did not have a beneficial effect on growth.


[Protective effect of propentophylline (HWA 285) in ischemic spinal cord injury].
The effect of propentophylline (HWA 285) on the course of the functional regeneration of the hind extremities and on the regeneration of the energetic metabolism in the spinal cord after ischaemia produced by ligating the abdominal aorta for 20 or 30 mins was investigated. Administration of 20 mg/kg i.v. propentophylline after the induction of ischaemia produced marked regeneration of these parameters in comparison with ischaemia without administration of the drug in the course of four days. The protective effect of propentophylline administered prior to ischaemia was markedly weaker.


Mortality and causes of death in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark.
A population-based cohort comprising 374 patients with Crohn's disease diagnosed in Copenhagen County between 1962 and 1987 was observed until 1997 for mortality and causes of death. Observed deaths were compared with expected deaths calculated by using individually computed person-years at risk and 1995 rates for Copenhagen County. Cumulative survival curves were calculated. A total of 84 deaths occurred vs. 67 expected (standardized mortality ratio [SMR], 1.3; 95% confidence interval [CI], 1.01-1.56): 45 women vs. 31.8 expected (SMR, 1.4; 95% CI, 1.03-1.89) and 39 men vs. 35.2 expected (SMR, 1.1; 95% CI, 0.79-1.51). An excess mortality was observed among women observed for 21-25 years after diagnosis. Among women aged <50 years at diagnosis, 25 deaths were observed vs. 7.3 expected (SMR, 3.42; 95% CI, 2.21-5.04). Fourteen (31%) of the observed deaths among women and 8 (21%) among men had a certain or possible connection to Crohn's disease. Among causes of death unrelated to Crohn's disease, an overrepresentation of gastrointestinal diseases, infections, and diseases of the urinary organs was observed. An increased mortality was observed late in the disease course that was most pronounced among women younger than 50 years at diagnosis and was attributed to death associated with severe Crohn's disease.