Characterizing microscopic and submicroscopic malaria parasitaemia at three sites with varied transmission intensity in Uganda.
Parasite prevalence is a key metric used to quantify the burden of malaria and assess the impact of control strategies. Most published estimates of parasite prevalence are based on microscopy and likely underestimate true prevalence. Thick smear microscopy was performed in cohorts of children (aged 6 month to 10 years) and adults every 90 days over 2 years, at three sites of varying transmission intensity in Uganda. Microscopy-negative samples were tested for sub-microscopic parasitaemia using loop-mediated isothermal amplification (LAMP). Generalized estimating equation models were used to evaluate associations between age and parasitaemia, factors associated with sub-microscopic infection and associations between parasitaemia and haemoglobin. A total of 9260 samples were collected from 1245 participants. Parasite prevalence among children across the three sites was 7.4, 9.4 and 28.8 % by microscopy and 21.3, 31.8 and 69.0 % by microscopy plus LAMP. Parasite prevalence among adults across the three sites was 3.1, 3.0 and 5.2 % by microscopy and 18.8, 24.2 and 53.5 % by microscopy plus LAMP. Among those with parasitaemia, adults and persons recently treated with anti-malarial therapy had the highest prevalence of sub-microscopic infection. Children with sub-microscopic or microscopic parasitaemia had lower mean haemoglobin levels compared to children with no detectable parasites. Across a range of transmission intensities in Uganda, microscopy vastly underestimated parasite prevalence, especially among adults.


Prolonged C1 inhibitor administration improves local healing of burn wounds and reduces myocardial inflammation in a rat burn wound model.
In a previous study, the authors found persistent presence of acute inflammation markers such as C-reactive protein and complement factors locally in burn wounds. This persistence of acute inflammation may not only delay local burn wound healing but also have a systemic effect, for instance on the heart. Here, the effects of C1 esterase inhibitor (C1inh), an inhibitor of complement activation, on burn wound progression and the heart were analyzed in rats. Dorsal full-thickness burn wounds (2 × 4 cm) were induced on female Wistar rats (n = 14). The rats were divided into two groups (n = 7): a control group (just burns) and a C1inh group. C1inh was administered daily intravenously for 14 days. The burn wound, healthy skin from the hind leg (internal control), and the heart were then fixed in formalin. Tissues were analyzed for granulation tissue formation, reepithelialization, amount and type of infiltrating inflammatory cells (granulocytes and macrophages), and inflammatory markers (complement factors C3 and C4). C1inh treatment significantly reduced the amount of granulation tissue and significantly increased reepithelialization. C1inh also significantly reduced macrophage infiltration. Burns induced infiltration of macrophages into the ventricles of the heart and remarkably also into the atria of the heart. This effect could be counteracted by C1inh. These data show that systemic treatment with C1inh acts at different levels resulting in improved healing locally in burn wounds and systemically reduced inflammation in the heart. Therefore, C1inh might be a possible therapeutic intervention for burn wound patients.


Adult obstructive sleep apnea: pathophysiology and diagnosis.
Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent episodes of upper airway obstruction that result in recurrent arousals and episodic oxyhemoglobin desaturations during sleep. Significant clinical consequences of the disorder cover a wide spectrum, including daytime hypersomnolence, neurocognitive dysfunction, cardiovascular disease, metabolic dysfunction, and cor pulmonale. The major risk factors for the disorder include obesity, male gender, and age. Current understanding of the pathophysiologic basis of the disorder suggests that a balance of anatomically imposed mechanical loads and compensatory neuromuscular responses are important in maintaining upper airway patency during sleep. OSA develops in the presence of both elevated mechanical loads on the upper airway and defects in compensatory neuromuscular responses. A sleep history and physical examination is important in identification of patients and appropriate referral for polysomnography. Understanding nuances in the spectrum of presenting complaints and polysomnography correlates are important for diagnostic and therapeutic approaches. Knowledge of common patterns of OSA may help to identify patients and guide therapy.


Chronic hypoxia alters glucose utilization during GSH-dependent detoxication in rat small intestine.
We showed that hypoxia alters glutathione (GSH)-dependent detoxication and induces mucosal metabolic instability. To determine the impact of these changes and the role of reductant supply in intestinal lipid peroxide disposition, pair-fed (16 g/day) Sprague-Dawley rats were exposed to air (20.9% O2; n = 6) or 10% O2 (n = 6) for 10 days. Jejunal and ileal everted sacs were exposed to 75 microM peroxidized fish oil with or without 10 mM glucose or 1 mM GSH. Peroxide transport was determined as the abluminal recovery of thiobarbituric acid-reactive substances. Peroxide recovery in hypoxic intestine was twice that in normoxic intestine. Addition of GSH and glucose did not affect peroxide recovery, indicating reduced intracellular GSH-dependent metabolism and enhanced output by the hypoxic intestine. Glucose uptake by normoxic and hypoxic intestine is similar, whereas its utilization for detoxication is decreased in hypoxic cells. Determination of NADPH supply indicates that decreased glucose availability for NADPH production during hypoxia impairs GSH disulfide reduction, compromises hydroperoxide metabolism, and increases peroxide output from hypoxic intestine.


A qualitative study exploring barriers to a model of shared care for pre-school children's oral health.
To explore the oral health beliefs and practices of primary health care professionals which may act as barriers to the development of a model of shared care for the oral health of pre-school children. Qualitative focus group discussions and semi-structured interviews. Four rural local government areas in Victoria, Australia, 2003. maternal and child health nurses, general medical practitioners, dental professionals and paediatricians working in the four local government areas. discipline specific focus groups and semi-structured interviews. transcription, coding, clustering and thematic analysis. Several strong themes emerged from the data. All participants agreed that dental caries is a significant health issue for young children and their families. Beliefs about the aetiology of dental caries and its prevention were variable and often simplistic focusing predominantly on diet. Dental professionals did not believe that they had a primary role in the oral health of pre-school aged children but that others particularly maternal and child health nurses did. However other health care professionals were not confident in assuming this role. This study has identified important barriers and possible strategies for the development of an integrated and shared approach to preventing dental caries in pre-school aged children. Clear and consistent oral health information and agreed roles and responsibilities need to be developed.


Decoupling Personality and Acute Psychiatric Symptoms in a Depressed Sample and a Community Sample.
The association between depression and neuroticism is complex, but due to the difficulty in assessing neuroticism during mood episodes, the mechanisms underlying this relationship remain poorly understood. In this study, we sought to decompose neuroticism into finer-grained elements that were uncorrelated with psychiatric symptoms and to examine the incremental validity of those elements in explaining deficits in interpersonal functioning. A bifactor model with one general factor and six specific factors fit the data well in both a depressed (N=807) and a community (N=1,284) sample, and the specific factors were relatively independent of acute symptoms. Moreover, two specific factors (Angry Hostility and Self-Consciousness) accounted for incremental variance in interpersonal functioning problems in the community sample and in a subgroup of depressed participants. The results demonstrate that neuroticism can be decomposed into components that are distinct from symptoms and that are incrementally associated with deficits in interpersonal functioning.


The individual preferred velocity of stroking touch as a stable measurement.
Affective touch is of fundamental importance in human social interactions and there is an increasing interest in using touch as a probe for general affective perception. To this end, we developed a test of preferred velocity (ToP-V) of touch and tested whether the individually preferred stroking velocity is a stable and valid measurement. In study one, thirty healthy participants (18-30years, 17 women) were examined with the ToP-V. Therefore, pairs of different slow stroking stimuli were presented by the Rotary Tactile Stimulator - a robotic device - on the forearm and the participants chose the velocity they preferred in a forced choice paradigm. A retest was conducted after about 12days. In study two, twenty-two healthy participants (20-43years, 11 women) were tested with a shorter version of the ToP-V on the forearm and also on the palm. Moreover, they rated the pleasantness and the intensity of the stroking stimulations on both body sites. Results suggest that humans possess an individual and stable preferred velocity of stroking touch (test-retest reliability r=0.86) which can be tested in a standardized procedure. A shortened 5min version of the ToP-V also exhibited reasonable test characteristics (split half reliability: r=0.7; test-retest reliability r=0.77). The ToP-V correlated well with the pleasantness ratings when tested on the forearm (r=0.65), but not when tested on the palm (r=-0.22), indicating that the ToP-V targets a C-tactile nerve fiber specific perception. Hence, the ToP-V can be used for reliably probing affective touch perception.


74-week follow-up of safety of infliximab in patients with refractory rheumatoid arthritis.
The objective was to describe the prevalence, types, and predictors of adverse events (AEs) in rheumatoid arthritis (RA) patients treated with infliximab and methotrexate in a daily clinical setting. This was a prospective, multi-center, open-label, 74-week observational study in patients with active RA despite treatment with methotrexate and at least one other disease-modifying anti-rheumatic drug. Patients were treated with 3 mg/kg infliximab at weeks 0, 2, and 6 and then every 8 weeks. At weeks 0, 6, 26, 50, and 74, patients answered a health assessment questionnaire, a swollen joint count was made, and adverse events (AEs) occurring during the previous period were registered. Five hundred and seventy-five patients were treated with infliximab, of which 346 were still on infliximab at the study end, 158 discontinued treatment, and 71 were lost to follow-up. Reasons for discontinuation included safety (n=74), elective reasons (n=43), and inefficacy (n=41). Infusion reactions (n=33) and infections (n=20) were the most common AEs causing discontinuation and the most common AEs overall. There were four cases of tuberculosis, all of which occurred in patients negative at screening. Total AEs, serious AEs, and infusion reactions as well as discontinuations for AEs were most frequent during the first 26 weeks. Higher age was a predictor of serious adverse events (SAEs), infection, and discontinuation due to an SAE, but odds ratios were close to one. AEs and discontinuations due to AEs occur most frequently during the first half year of infliximab treatment in refractory RA patients. The main reasons for discontinuing treatment are infections and infusion reactions. Tuberculosis and other infections remain an important concern in these patients.


Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome.
The pathophysiology of irritable bowel syndrome (IBS) is not completely understood. However, several factors are known to play a role in pathophysiology of IBS such as genetics, diet, gut microbiota, gut endocrine cells, stress and low-grade inflammation. Understanding the pathophysiology of IBS may open the way for new treatment approaches. Low density of intestinal stem cells and low differentiation toward enteroendocrine cells has been reported recently in patients with IBS. These abnormalities are believed to be the cause of the low density of enteroendocrine cells seen in patients with IBS. Enteroendocrine cells regulate gastrointestinal motility, secretion, absorption and visceral sensitivity. Gastrointestinal dysmotility, abnormal absorption/secretion and visceral hypersensitivity are all seen in patients with IBS and haven been attributed to the low density the intestinal enteroendocrine cells in these patients. The present review conducted a literature search in Medline (PubMed) covering the last ten years until November 2019, where articles in English were included. Articles about the intestinal stem cells and their possible role in the pathophysiology of IBS are discussed in the present review. The present review discusses the assumption that intestinal stem cells play a central role in the pathophysiology of IBS and that the other factors known to contribute to the pathophysiology of IBS such as genetics, diet gut microbiota, stress, and low-grade inflammation exert their effects through affecting the intestinal stem cells. It reports further the data that support this assumption on genetics, diet, gut microbiota, stress with depletion of glutamine, and inflammation.


The domestic violence survivor assessment: a tool for counseling women in intimate partner violence relationships.
Seeking to end violence and distress in their relationship is the goal of women abused by intimate partners. The theoretical framework guiding development of the domestic violence survivor assessment (DVSA) was Landenburger's theory of entrapment and recovery. Social context and need to balance care for others and herself influence women's decision-making about abuse. The DVSA was developed collaboratively between researchers and counselors to gain a deeper understanding of battered women's cognitive states in order to assist them during counseling to effectively resolve the dilemma of their abusive relationships while experiencing personal growth. Five states are identified which a woman may experience on 11 issues concurrently at the personal, relationship or social context levels. Research to validate the DVSA and suggestions on use with women desiring to preserve their relationship or preserve their self or preserve the resolution of change is described. Using the DVSA for assessment, intervention and measuring intermediate outcomes is delineated.


Cardiac function and posttraumatic stress disorder: a review of the literature and case report.
Posttraumatic stress disorder (PTSD) can induce an elevation in sympathetic tone; however, research pertaining to the cardiac cycle in patients with PTSD is limited. A literature review was conducted with PubMed, MEDLINE and Web of Science. Articles discussing changes and associations in echocardiography and PTSD or related symptoms were synthesized for the current review. We have also included data from a case report of a male participant aged 33 years experiencing potentially psychologically traumatic events, who wore a noninvasive cardiac sensor to assess the timing intervals and contractility parameters of the cardiac cycle using seismocardiography. The intervals included systolic time, isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT). Calculations of systolic (IVCT/systole), diastolic (IVRT/systole) and myocardial [(IVCT+IVRT)/systole] performance indices were completed. The review identified 55 articles, 14 of which assessed cardiac function using echocardiography in patients with PTSD symptoms. Cardiac dysfunction varied across studies, with diastolic and systolic impairments found in patients with PTSD. Our case study showed that occupational stress elevated cardiac performance indices, suggesting increased ventricular stress and supporting results in the existing literature. The literature review results suggest that a controlled approach to assessing cardiac function in patients with PTSD is required. The case study results further suggest that acute bouts of stress can alter cardiac function, with potential for sustained occupational stress to induce changes in cardiac function. Cardiac monitoring can be used prospectively to identify changes induced by potentially psychologically traumatic event exposures that can lead to the development of PTSD symptoms.


Unsung questions of medical ethics.
Official doctrines of medical ethics have become increasingly 'patient-centered': physicians are exhorted to respect patients' autonomy and to encourage patient participation in decision making; physicians in general medicine and primary care, especially, are urged to develop psychosocial competence, cross-cultural sensitivity and communications skills. These official values are undermined and contradicted, however, by the routines and assumptions that physicians use to organize their everyday work. These routines are taken so for granted as natural and required for the smooth, orderly practice of medicine that they escape evaluation for the implicit values they contain. Yet, they reinforce a particular view of appropriate roles and responsibilities for both physician and patient in the medical system, including the agenda and purpose of the medical interview; the level and amount of information to share with patients; and the power structure of the physician-patient relationship. These values, hidden in the routines of daily practice, are unsung questions of medical ethics. A fallacy in calls for greater patient participation in medical care is that this participation can flourish by simple addition, without reform of the ordinary structures of everyday practice. It is unlikely that these structures will change unless their normally invisible value commitments are drawn out of the obscurity of routine, and made subjects for public scrutiny and choice.


High-energy diets may induce a pre-diabetic state altering testicular glycolytic metabolic profile and male reproductive parameters.
Diabetes mellitus is a metabolic disorder that may arise from diet habits and is growing to epidemic proportions. Young male diabetic patients present high infertility/subfertility prevalence resulting from impaired reproductive function and poor semen quality. We aimed to evaluate the effects of a high-energy diet (HED) on glucose tolerance/insulin levels and correlate the observed effects on male reproductive function with overall testicular metabolism. After 1 month, HED fed rats showed increased glycaemic levels, impaired glucose tolerance and hypoinsulinaemia. Moreover, an imbalance of intratesticular and serum testosterone levels was observed, whereas those of 17β-estradiol were not altered. High-energy diet also affected the reproductive parameters, with HED rats exhibiting a significant increase in abnormal sperm morphology. Glycolytic metabolism was favoured in testicles of HED rats with an increased expression of both glucose transporters 1 (GLUT1) and 3 (GLUT3) and the enzyme phosphofrutokinase 1. Moreover, lactate production and the expression of metabolism-associated genes and proteins involved in lactate production and transport were also enhanced by HED. Alanine testicular content was decreased and thus intratesticular lactate/alanine ratio in HED rats was increased, suggesting increased oxidative stress. Other energetic substrates such as acetate and creatine were not altered in testis from HED rats, but intratesticular glycine content was increased in those animals. Taken together, these results suggest that HED induces a pre-diabetic state that may impair reproductive function by modulating overall testicular metabolism. This is the first report on testicular metabolic features and mechanisms related with the onset of a pre-diabetic state.


Characterization of polypeptides synthesized and secreted by oviductal epithelial cell explants obtained from young, fertile and aged, subfertile mares.
To compare the electrophoretic patterns of proteins synthesized and secreted by oviductal epithelial cell (OEC) explants obtained from young, fertile and aged, subfertile mares. Young, fertile (n = 5; 2 to 7 years old) and aged, subfertile (n = 5; 17 to 24 years old) mares. 2-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and computerized densitometry. Variation in the synthesis and secretion of polypeptides from young, fertile mare OEC (YOEC) and aged, subfertile mare OEC (AOEC) was evidenced by differences in the intensity of radiolabeled polypeptides on fluorograms. Fluorograms for 9 acidic (isoelectric point, 5.09 to 6.50) proteins of low to medium molecular mass (18.2 to 85.0 kd) from YOEC had greater intensity than did those from AOEC. Fluorograms for 7 proteins (10.5 to 45.0 kd; isoelectric point, 5.80 to 6.92) from AOEC had greater intensity. The differences detected in the fluorographic intensities of secreted proteins from YOEC and AOEC may be related to the disparity in embryo development observed between young, fertile and aged, subfertile mares. Failure to maintain pregnancy in aged, subfertile mares may be a result of a suboptimal oviductal environment exerting its effects on the conceptus during early cleavage.


Nucleases isolated from Chelidonium majus L. milky sap can induce apoptosis in human cervical carcinoma HeLa cells but not in Chinese Hamster Ovary CHO cells.
Milky sap isolated from Chelidonium majus L. (Greater Celandine) serves as a rich source of various biologically active substances such as alkaloids, flavonoids and phenolic acids. Previous research showed that the activity of Ch. majus milky sap may depend also on the presence of biologically active proteins. The goal of this study was to evaluate the biological effect of two nucleases isolated from Ch. majus milk sap, CMN1 of 20 kDa and CMN2 of 36 kDa, on HeLa and CHO tumour cell lines. Both studied nucleases together with other proteins in the sap of the plant are involved in stress and defence reactions against different pathogens. After 48 h incubation of CMN1 and CMN2 only with HeLa cells, the dependence between the number of apoptotic lesions and the concentration of applied nuclease was observed. The highest proapoptotic activity was induced by 13.3 ng/ml concentration of CMN2 collected in May (62 +/- 3% HeLa cells were apoptotic). Moreover, the proportion of necrotic cells in all concentrations of the nucleases and both cell lines was relatively low (1-8 +/- 0.5%). In summary, results of this study show that purified nucleases CMN1 and CMN2 isolated from Ch. majus milky sap exhibit apoptotic activity in HeLa tumour cell line, but not in CHO cells, without inflammatory reaction.


Spreading rate dependence of gravity anomalies along oceanic transform faults.
Mid-ocean ridge morphology and crustal accretion are known to depend on the spreading rate of the ridge. Slow-spreading mid-ocean-ridge segments exhibit significant crustal thinning towards transform and non-transform offsets, which is thought to arise from a three-dimensional process of buoyant mantle upwelling and melt migration focused beneath the centres of ridge segments. In contrast, fast-spreading mid-ocean ridges are characterized by smaller, segment-scale variations in crustal thickness, which reflect more uniform mantle upwelling beneath the ridge axis. Here we present a systematic study of the residual mantle Bouguer gravity anomaly of 19 oceanic transform faults that reveals a strong correlation between gravity signature and spreading rate. Previous studies have shown that slow-slipping transform faults are marked by more positive gravity anomalies than their adjacent ridge segments, but our analysis reveals that intermediate and fast-slipping transform faults exhibit more negative gravity anomalies than their adjacent ridge segments. This finding indicates that there is a mass deficit at intermediate- and fast-slipping transform faults, which could reflect increased rock porosity, serpentinization of mantle peridotite, and/or crustal thickening. The most negative anomalies correspond to topographic highs flanking the transform faults, rather than to transform troughs (where deformation is probably focused and porosity and alteration are expected to be greatest), indicating that crustal thickening could be an important contributor to the negative gravity anomalies observed. This finding in turn suggests that three-dimensional magma accretion may occur near intermediate- and fast-slipping transform faults.


Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates.
Developmental responses to auxin are regulated by facilitated uptake and efflux, but detailed molecular understanding of the carrier proteins is incomplete. We have used pharmacological tools to explore the chemical space that defines substrate preferences for the auxin uptake carrier AUX1. Total and partial loss-of-function aux1 mutants were assessed against wild-type for dose-dependent resistance to a range of auxins and analogues. We then developed an auxin accumulation assay with associated mathematical modelling to enumerate accurate IC50 values for a small library of auxin analogues. The structure activity relationship data were analysed using molecular field analyses to create a pharmacophoric atlas of AUX1 substrates. The uptake carrier exhibits a very high level of selectivity towards small substrates including the natural indole-3-acetic acid, and the synthetic auxin 2,4-dichlorophenoxyacetic acid. No AUX1 activity was observed for herbicides based on benzoic acid (dicamba), pyridinyloxyacetic acid (triclopyr) or the 6-arylpicolinates (halauxifen), and very low affinity was found for picolinic acid-based auxins (picloram) and quinolinecarboxylic acids (quinclorac). The atlas demonstrates why some widely used auxin herbicides are not, or are very poor substrates. We list molecular descriptors for AUX1 substrates and discuss our findings in terms of herbicide resistance management.


Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials.
Urinary tract infection (UTI) is one of the most commonly acquired bacterial infections. Cranberry-containing products have long been used as a folk remedy to prevent UTIs. The aims of this study were to evaluate cranberry-containing products for the prevention of UTI and to examine the factors influencing their effectiveness. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systemically searched from inception to November 2011 for randomized controlled trials that compared prevention of UTIs in users of cranberry-containing products vs placebo or nonplacebo controls. There were no restrictions for language, population, or publication year. Thirteen trials, including 1616 subjects, were identified for qualitative synthesis from 414 potentially relevant references; 10 of these trials, including a total of 1494 subjects, were further analyzed in quantitative synthesis. The random-effects pooled risk ratio (RR) for cranberry users vs nonusers was 0.62 (95% CI, 0.49-0.80), with a moderate degree of heterogeneity (I(2) = 43%) after the exclusion of 1 outlier study. On subgroup analysis, cranberry-containing products seemed to be more effective in several subgroups, including women with recurrent UTIs (RR, 0.53; 95% CI, 0.33-0.83) (I(2) = 0%), female populations (RR, 0.49; 95% CI, 0.34-0.73) (I(2) = 34%), children (RR, 0.33; 95% CI, 0.16-0.69) (I(2) = 0%), cranberry juice drinkers (RR, 0.47; 95% CI, 0.30-0.72) (I(2) = 2%), and subjects using cranberry-containing products more than twice daily (RR, 0.58; 95% CI, 0.40-0.84) (I(2) = 18%). Our findings indicate that cranberry-containing products are associated with protective effect against UTIs. However, this result should be interpreted in the context of substantial heterogeneity across trials.


Dislocation-driven nanowire growth and Eshelby twist.
Hierarchical nanostructures of lead sulfide nanowires resembling pine trees were synthesized by chemical vapor deposition. Structural characterization revealed a screwlike dislocation in the nanowire trunks with helically rotating epitaxial branch nanowires. It is suggested that the screw component of an axial dislocation provides the self-perpetuating steps to enable one-dimensional crystal growth, in contrast to mechanisms that require metal catalysts. The rotating trunks and branches are the consequence of the Eshelby twist of screw dislocations with a dislocation Burgers vector along the 110 directions having an estimated magnitude of 6 +/- 2 angstroms for the screw component. The results confirm the Eshelby theory of dislocations, and the proposed nanowire growth mechanism could be general to many materials.


DSMZCellDive: Diving into high-throughput cell line data.
Human and animal cell lines serve as model systems in a wide range of life sciences such as cancer and infection research or drug screening. Reproducible data are highly dependent on authenticated, contaminant-free cell lines, no better delivered than by the official and certified biorepositories. Offering a web portal to high-throughput information on these model systems will facilitate working with and comparing to these references by data otherwise dispersed at different sources. We here provide DSMZCellDive to access a comprehensive data source on human and animal cell lines, freely available at celldive.dsmz.de. A wide variety of data sources are generated such as RNA-seq transcriptome data and STR (short tandem repeats) profiles. Several starting points ease entering the database via browsing, searching or visualising. This web tool is designed for further expansion on meta and high-throughput data to be generated in future. Explicated examples for the power of this novel tool include analysis of B-cell differentiation markers, homeo-oncogene expression, and measurement of genomic loss of heterozygosities by an enlarged STR panel of 17 loci. Sharing the data on cell lines by the biorepository itself will be of benefit to the scientific community since it (1) supports the selection of appropriate model cell lines, (2) ensures reliability, (3) avoids misleading data, (4) saves on additional experimentals, and (5) serves as reference for genomic and gene expression data.


Stem cell therapies to treat muscular dystrophy: progress to date.
Muscular dystrophies are heritable, heterogeneous neuromuscular disorders and include Duchenne and Becker muscular dystrophies (DMD and BMD, respectively). DMD patients exhibit progressive muscle weakness and atrophy followed by exhaustion of muscular regenerative capacity, fibrosis, and eventually disruption of the muscle tissue architecture. In-frame mutations in the dystrophin gene lead to expression of a partially functional protein, resulting in the milder BMD. No effective therapies are available at present. Cell-based therapies have been attempted in an effort to promote muscle regeneration, with the hope that the host cells would repopulate the muscle and improve muscle function and pathology. Injection of adult myoblasts has led to the development of new muscle fibers, but several limitations have been identified, such as poor cell survival and limited migratory ability. As an alternative to myoblasts, stem cells were considered preferable for therapeutic applications because of their capacity for self-renewal and differentiation potential. In recent years, encouraging results have been obtained with adult stem cells to treat human diseases such as leukemia, Parkinson's disease, stroke, and muscular dystrophies. Embryonic stem cells (ESCs) can be derived from mammalian embryos in the blastocyst stage, and because they can differentiate into a wide range of specialized cells, they hold potential for use in treating almost all human diseases. Several ongoing studies focus on this possibility, evaluating differentiation of specific cell lines from human ESCs (hESCs) as well as the potential tumorigenicity of hESCs. The most important limitation with using hESCs is that it requires destruction of human blastocysts or embryos. Conversely, adult stem cells have been identified in various tissues, where they serve to maintain, generate, and replace terminally differentiated cells within their specific tissue as the need arises for cell turnover or from tissue injury. Moreover, these cells can participate in regeneration of more than just their specific tissue type. Here we describe multiple types of muscle- and fetal-derived myogenic stem cells, their characterization, and their possible use in treating muscular dystrophies such as DMD and BMD. We also emphasize that the most promising possibility for the management and therapy of DMD and BMD is a combination of different approaches, such as gene and stem cell therapy.


Enhancement of red cell washout from blood clots by alteration of gel pore size and red cell flexibility.
Plasma clots formed in the presence of erythrocytes have pores large enough to allow significant perfusion induced washout of red cells. Erythrocyte washout is a function of gel pore size and erythrocyte flexibility. This study evaluated the possibility of increasing cell washout by enhancing gel pore size and/or erythrocyte flexibility. Addition of increasing concentrations of Dextran 40 resulted in gels composed of large fibers with large intervening pores. Gel fiber mass-to-length ratios increased from 2.6 to 8.1 x 10(13) Da/cm as Dextran 40 concentration increased from 0 to 12 mg/ml. Over the same dextran concentration range, perfusion measurements revealed an increase in gel pore diameter from 1.4 to 3.5 x 10(-4) cm and an increase in erythrocyte washout from 8.2 to 30.4% during a 1.5 gel volume exchange. Pentoxifylline was added to blood to enhance erythrocyte flexibility. Whereas turbidity measurements indicated minimal direct impact of pentoxifylline (50 micrograms/ml) on fibrin assembly or structure, perfusion measurements indicated an increase in erythrocyte washout from 8.1 to 13.4% after a 1.5 gel volume exchange. Efforts to evaluate pentoxifylline effects at higher concentrations were hampered by decreased adhesion of the gel to the sides of the perfusion chamber. These results indicate that it may be possible to enhance erythrocyte washout and thereby increase diffusion and perfusion of materials through in situ clots.


'Hesitant compliers': Qualitative analysis of concerned fully-vaccinating parents.
Some parents are hesitant about vaccines and yet still vaccinate their children. Vaccine behaviours are not fixed and parents who are concerned but nonetheless adherent to standard schedules could switch to an unconventional schedule, delaying or cherry-picking vaccines. There is a need to better understand vaccine hesitancy in specific contexts, acknowledging cultural and geographical variation, to ensure interventions targeting hesitancy are well directed and received. To identify the behaviours, knowledge and attitudes of 'hesitant compliers' in Perth, Western Australia, nine one-on-one in-depth interviews were conducted with vaccinating parents of children (<5 years) who were identified as being hesitant. Interview transcripts were analysed qualitatively and themes developed inductively, following a constructivist paradigm. Parents saw vaccination as important for themselves and their community, despite their limited knowledge of vaccine preventable diseases. Parents reported concerns about potential side effects, and worried about the safety of the measles-mumps-rubella (MMR) and seasonal influenza vaccines. Concerned about the role of anti-vaccination information in the community, some sought to isolate themselves from parents who did not vaccinate, although others were concerned that this could entrench non-vaccinators' behaviours. Parents' views were all underlaid by two pivotal 'vaccine-related events' that had occurred in the community: the severe injury of a baby from seasonal influenza vaccination in 2010, and the death of a baby from whooping cough in 2015. Parents interpreted pivotal vaccine-related events in the community as requiring them to take personal responsibility for vaccine decisions. Their reports of continued vaccine fears (evident in international studies in recent decades) demonstrate that vaccine scares have long lasting effects. With vaccine rates high and stable, current strategies appear to be have little impact on addressing parental vaccine concerns. Further research is required to determine the prevalence of hesitancy amongst vaccinating parents and identify critical points for intervention.


Autophagic removal of micronuclei.
Macroautophagy is known to participate in the quality control and turnover of cytoplasmic organelles, yet there is little evidence that macroautophagy targets nuclei in mammalian cells. Here, we investigated whether autophagy may target micronuclei, which arise as a result of deficient bipolar chromosome segregation in cells exposed to cell cycle perturbations. After removal of several distinct cell cycle blockers (nocodazole, cytochalasin D, hydroxyurea or SP600125), cells manifested an increase in the frequency of micronuclei (positive for histone H2B-RFP) as well as an increase in autophagic puncta (positive for GFP-LC3) over several days. A small but significant percentage of micronuclei co-localized with GFP-LC3 in autophagy-competent cells and this co-localization was lost after knockdown of ATG5 or ATG7. Electron microscopy analyses confirmed autophagic sequestration of micronuclei. "Autophagic micronuclei" (GFP-LC3⁺) were also decorated with p62/SQSTM1, while non-autophagic (GFP-LC3⁻) micronuclei where p62/SQSTM1 negative. In addition, GFP-LC3⁺ micronuclei exhibited signs of envelope degradation and γH2AX⁺ DNA damage foci, yet stained less intensively for chromatin markers, whereas GFP-LC3⁻ micronuclei were surrounded by an intact envelope and rarely exhibited markers or DNA damage. These results indicate that micronuclei can be subjected to autophagic degradation. Moreover, it can be speculated that removal of micronuclei may contribute to the genome-stabilizing effects of autophagy.


Tear in mitral anterior leaflet as a complication of Manouguian's procedure in a woman with an aortic valve prosthesis.
Complications of valve replacement are diverse. In addition to morbidity due to the prosthetic valve itself (e.g. endocarditis, thrombosis), complications due to operative technique may occur in complex cases, as in aortic valve replacement with annular enlargement. Postoperative echocardiography is a simple, non-invasive method to evaluate patients with prosthetic valves. Detailed knowledge of the surgical technique employed and of probable complications is necessary to make an accurate diagnosis. The case is reported of a woman with aortic valve replacement and annular enlargement who had mitral regurgitation due to a tear in the anterior mitral leaflet as a complication of Manouguian's annulus enlargement.


Molecular crosstalks in Leishmania-sandfly-host relationships.
Sandflies (Diptera: Phlebotominael are vectors of Leishmania parasites, causative agents of important human and animal diseases with diverse manifestations. This review summarizes present knowledge about the vectorial part of Leishmania life cycle and parasite transmission to the vertebrate host. Particularly, it focuses on molecules that determine the establishment of parasite infection in sandfly midgut. It describes the concept of specific versus permissive sandfly vectors, explains the epidemiological consequences of broad susceptibility of permissive sandflies and demonstrates that genetic exchange may positively affect Leishmania fitness in the vector. Last but not least, the review describes recent knowledge about circulating antibodies produced by hosts in response to sandfly bites. Studies on specificity and kinetics of antibody response revealed that anti-saliva IgG could be used as a marker of host exposure to sandflies, i.e. as a useful tool for evaluation of vector control.


Suicide risk in trans populations: An application of minority stress theory.
Drawing on minority stress theory, the present study tested the relations of minority stressors (i.e., experiences of prejudice and discrimination, internalized antitrans attitudes, fear of antitrans stigma), social support (i.e., friend, family, and significant other support), and substance use (i.e., drug and alcohol use) with depression and suicide risk in a sample of trans individuals. Depression was examined as a mediator of the relations of minority stressors and social support with suicide risk; drug and alcohol use were examined as direct correlates of suicide risk. Participants were 335 trans-identified individuals, diverse in gender identities (e.g., trans men, trans women, nonbinary gender identities). They were recruited using online social networks and they completed the study survey online via Qualtrics. Structural equation modeling was used to test hypothesized relations. Depression fully mediated the relations of perceived experiences of discrimination, fear of antitrans stigma, and friend support with suicide risk, and partially mediated the relation of internalized antitrans attitudes with suicide. Drug use was positively associated with suicide risk, whereas alcohol use was not linked with suicide risk. Exploratory comparisons across gender subgroups suggested that the pattern of relations among study variables was consistent across trans men, trans women, and individuals with nonbinary gender identities. These findings point to minority stressors, friend support, and drug use as potentially fruitful targets of prevention and intervention efforts to reduce depression and suicide risk in trans populations. (PsycINFO Database Record


Cancer cell and macrophage cross-talk in the tumor microenvironment.
Tumors are composed of tumor cells, nonmalignant cells, and the vascular system. Among them is intense communication via cell-cell contact-dependent mechanisms and/or soluble messengers. In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming. Nutrient stress also provokes autophagy to guarantee cell survival or, if overwhelmed, to exit toward cell demise. Death of tumor cells turned out as a communicative system attracting macrophages and directing their phenotype. Depending on the mode of tumor cell death macrophage polarization ranges from the extremes of pro-inflammatory activation toward anti-inflammatory/immuno-suppressive activation. Here we discuss how hypoxia and cell death adds the cross-talk between cancer cells and macrophages.


Perineural invasion on prostate biopsy does not predict adverse pathological outcome.
The clinical significance of perineural invasion (PNI) on prostate needle biopsy is controversial. The aim of this present study is to determine the role of PNI on prostate biopsy in predicting adverse findings at radical prostatectomy in a recent cohort of screen detected prostate cancer. We analyzed 470 patients diagnosed with prostate cancer from a prospectively maintained database at Princess Margaret Hospital. Out of the 470 patients diagnosed with prostate cancer, 139 underwent radical prostatectomy. Pathological specimens were examined, and perineural invasion was identified as carcinoma tracking along or around a nerve in the perineural space. We investigated the predictive value of PNI on biopsy with PNI on radical prostatectomy as well as the ability of PNI on prostate biopsy to predict adverse findings at radical prostatectomy. Perineural invasion was present in 124 (26%) of biopsy specimens diagnosed with prostate cancer and 94 (68%) of those who chose radical prostatectomy. Perineural invasion on prostate needle biopsy was not predictive of radical prostatectomy Gleason score (p = .377), pathological stage (p = .852), extraprostatic extension (p = .258), surgical margin (p = .079), lymphovascular invasion (p = .499), and upgrading (p = .514) or downgrading (p = .208) at radical prostatectomy. The sensitivity, specificity, positive predictive value, and negative predictive value of PNI on biopsy for PNI on radical prostatectomy were 32%, 82%, 79%, and 37% respectively. The Cohen's Kappa correlation coefficient was .11. Perineural invasion on prostate needle biopsy is not predictive of radical prostatectomy outcome. Furthermore, perineural invasion on biopsy has limited predictive value for perineural invasion at radical prostatectomy.


A novel, multiplexed, probe-based quantitative PCR assay for the soybean root- and stem-rot pathogen, Phytophthora sojae, utilizes its transposable element.
Phytophthora root rot of soybean [Glycine max (L.) Merr.] is caused by the oomycete Phytophthora sojae (Kaufm. & Gerd.). P. sojae has a narrow host range, consisting primarily of soybean, and it is a serious pathogen worldwide. It exists in root and stem tissues as mycelium, wherein it can form oospores which subsequently germinate to release motile, infectious zoospores. Molecular assays detecting DNA of P. sojae are useful in disease diagnostics, and for determining the presence of the organism in host tissues, soils, and runoff or ponded water from potentially infested fields. Such assays as published have utilized ITS sequences from the nuclear ribosomal RNA genes in conventional PCR or dye-binding quantitative PCR (Q-PCR) but are not amenable to multiplexing, and some of these assays did not utilize control strategies for type I or type II errors. In this study, we describe primers and a bifunctional probe with specificity to a gypsy-like retroelement in the P. sojae genome to create a fluorogenic 5'-exonuclease linear hydrolysis assay, with a multiplexed internal control reaction detecting an exogenous target to validate negative calls, and with uracil-deglycosylase-mediated protection against carryover contamination. The assay specifically detected 13 different P. sojae isolates, and excluded 17 other Phytophthora species along with 20 non-Phytophthora fungal and oomycete species pathogenic on soybean. A diagnostic limit of detection of 34 fg total P. sojae DNA was observed in serial dilutions, equivalent to 0.3 genome, and a practical detection sensitivity of four zoospores per sample was achieved, despite losses during DNA extraction.


Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition.
The key transporter responsible for hepatic uptake of bile acids from portal circulation is Na+-taurocholate cotransporting polypeptide (NTCP, SLC10A1). This transporter is thought to be critical for the maintenance of enterohepatic recirculation of bile acids and hepatocyte function. Therefore, functionally relevant polymorphisms in this transporter would be predicted to have an important impact on bile acid homeostasis/liver function. However, little is known regarding genetic heterogeneity in NTCP. In this study, we demonstrate the presence of multiple single nucleotide polymorphisms in NTCP in populations of European, African, Chinese, and Hispanic Americans. Specifically four nonsynonymous single nucleotide polymorphisms associated with a significant loss of transport function were identified. Cell surface biotinylation experiments indicated that the altered transport activity of T668C (Ile223-->Thr), a variant seen only in African Americans, was due at least in part to decreased plasma membrane expression. Similar expression patterns were observed when the variant alleles were expressed in HepG2 cells, and plasma membrane expression was assessed using immunofluorescence confocal microscopy. Interestingly the C800T (Ser267-->Phe) variant, seen only in Chinese Americans, exhibited a near complete loss of function for bile acid uptake yet fully normal transport function for the non-bile acid substrate estrone sulfate, suggesting this position may be part of a region in the transporter critical and specific for bile acid substrate recognition. Accordingly, our study indicates functionally important polymorphisms in NTCP exist and that the likelihood of being carriers of such polymorphisms is dependent on ethnicity.


Immune Checkpoint Inhibitor Therapy-related Pneumonitis: Patterns and Management.
In recent years, the use of immune checkpoint inhibitor (ICI) therapy has rapidly grown, with increasing U.S. Food and Drug Administration approvals of a variety of agents used as first- and second-line treatments of various malignancies. ICIs act through a unique mechanism of action when compared with those of conventional chemotherapeutic agents. ICIs target the cell surface receptors cytotoxic T-lymphocyte antigen-4, programmed cell death protein 1, or programmed cell death ligand 1, which result in immune system-mediated destruction of tumor cells. Immune-related adverse events are an increasingly recognized set of complications of ICI therapy that may affect any organ system. ICI therapy-related pneumonitis is an uncommon but important complication of ICI therapy, with potential for significant morbidity and mortality. As the clinical manifestation is often nonspecific, CT plays an important role in diagnosis and triage. Several distinct radiographic patterns of pneumonitis have been observed: (a) organizing pneumonia, (b) nonspecific interstitial pneumonia, (c) hypersensitivity pneumonitis, (d) acute interstitial pneumonia-acute respiratory distress syndrome, (e) bronchiolitis, and (f) radiation recall pneumonitis. Published guidelines outline the treatment of ICI therapy-related pneumonitis based on the severity of symptoms. Treatment is often effective, although recurrence is possible. This article reviews the mechanism of ICIs and ICI therapy complications, with subsequent management techniques and illustrations of the various radiologic patterns of ICI-therapy related pneumonitis.©RSNA, 2019.


Toward elimination of Haemophilus influenzae type B carriage and disease among high-risk American Indian children.
This report describes the epidemiology of Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal colonization among Navajo and White Mountain Apache children younger than 7 years in an era of widespread immunization. We conducted active surveillance for invasive H influenzae disease from 1992 to 1999 and an oropharyngeal carriage study from 1997 to 1999. The predominant vaccine used was PedvaxHib. The average annual incidence of invasive Hib disease among children younger than 24 months was 22 cases per 100,000. Of 381 children younger than 7 years, only 1 (0.3%; 95% confidence interval = 0.0%, 1.3%) was colonized with Hib; 370 (97%) had received 2 or more doses of Hib conjugate vaccine. Among Navajo and White Mountain Apache children, Hib conjugate vaccines have led to a sustained reduction in invasive Hib disease and a reduction in oropharyngeal Hib carriage. The disease incidence among children younger than 24 months remains 20 times higher than in the general US population. Hib elimination will require additional characterization of colonization and disease in these high-risk populations.


Microvascular Patch Graft Angioplasty of the Common Carotid Arteries in Rats.
Microvascular patch graft angioplasty is one of the most important revascularization techniques in cerebrovascular neurosurgery. It is necessary for surgeons to develop the microvascular patch graft angioplasty technique in the laboratory before performing it in a real human body. To provide a training model for microvascular patch graft angioplasty of the common carotid arteries (CCAs) in rats. Using male Sprague-Dawley rats (n=20), an oval-shaped arterial patch 3 mm in length and 1.2 mm in width was prepared from a segment of left CCA, and a linear longitudinal arteriotomy 3 mm in length was made along the anterior aspect of the right CCA, then the arterial patch graft was anastomosed to the right CCA with 10-0 sutures in an interrupted fashion. Patency was assessed immediately and 30 minutes after the procedure. All microvascular patch graft angioplasties of the rat common carotid arteries were successful, and all the patency rates immediately after the operation and thirty minutes after the restoration of blood flow were 100%. The training model for microvascular patch angioplasty with rat CCAs can serve as a training tool for mastering the procedure, and this technique could provide an alternative strategy for the surgical repair of microvascular aneurysms and microvascular vessel injuries.


Demonstration of specific binding sites for 3H-RRR-alpha-tocopherol on human erythrocytes.
Previous work from our laboratory demonstrated specific binding sites for 3H-RRR-alpha-tocopherol (3H-d alpha T) in membranes of rat adrenal cells. As tocopherol deficiency is associated with increased susceptibility of red blood cells to hemolysis, we investigated tocopherol binding sites in human RBCs. Erythrocytes were found to have specific binding sites for 3H-d alpha T that exhibited saturability and time and cell-concentration dependence as well as reversibility of binding. Kinetic studies of binding demonstrated two binding sites--one with high affinity (Ka of 2.6 x 10(7) M-1), low capacity (7,600 sites per cell) and the other with low affinity (1.2 x 10(6) M-1), high capacity (150,000 sites per cell). In order to localize the binding sites further, RBCs were fractionated and greater than 90% of the tocopherol binding was located in the membranes. Similar to the findings in intact RBCs, the membranes exhibited two binding sites with a respective Ka of 3.3 x 10(7) M-1 and 1.5 x 10(6) M-1. Specificity data for binding demonstrated 10% binding for RRR-gamma-tocopherol, but not other tocopherol analog exhibited competition for 3H-d alpha T binding sites. Instability data suggested a protein nature for these binding sites. Preliminary studies on Triton X-100 solubilized fractions resolved the binding sites to a major component with an Mr of 65,000 and a minor component with an Mr of 125,000. We conclude that human erythrocyte membranes contain specific binding sites for RRR-alpha-tocopherol. These sites may be of physiologic significance in the function of tocopherol on the red blood cell membrane.


Contribution of water-soluble extracts to the oxidative and inflammatory effects of atmospheric aerosols: A critical review.
Exposure to atmospheric particulate matter (PM) has been associated with heightened risks of lung cancer, cardiovascular and respiratory diseases. PM exposure also affects the immune system, leading to an increased susceptibility to infections, exacerbating pre-existent inflammatory and allergic lung diseases. Atmospheric PM can primarily impact human health through the generation of reactive oxygen species (ROS) that subsequently induce or exacerbate inflammation. These cytotoxic effects have been related with PM concentration, and its chemical constituents, including metals, solvent extractable organics (e.g., polycyclic aromatic hydrocarbons), and water-soluble ions. Although not receiving much attention, the fine aerosol water-soluble organic matter (WSOM) can account for a substantial portion of the overall fine PM mass and has been shown to present strong oxidative and immunomodulatory effects. Thus, the objective of this review is to provide a comprehensive analysis of the role of the water-soluble fraction of PM, with a specific focus on the contribution of the WSOM component to the cytotoxic properties of atmospheric PM. The chemical properties of the water-soluble PM fraction are briefly discussed, while emphasis is put on how PM size, composition, and temporal variations (e.g., seasonality) can impact the pro-oxidative activity, the modulation of inflammatory response, and the cytotoxicity of the water-soluble PM extracts.


Tyrosine-phosphorylated caveolin-1 (Tyr-14) increases sensitivity to paclitaxel by inhibiting BCL2 and BCLxL proteins via c-Jun N-terminal kinase (JNK).
Paclitaxel, an anti-microtubule agent, is an effective chemotherapeutic drug in breast cancer. Nonetheless, resistance to paclitaxel remains a major clinical challenge. The need to better understand the resistant phenotype and to find biomarkers that could predict tumor response to paclitaxel is evident. In estrogen receptor α-positive (ER(+)) breast cancer cells, phosphorylation of caveolin-1 (CAV1) on Tyr-14 facilitates mitochondrial apoptosis by increasing BCL2 phosphorylation in response to low dose paclitaxel (10 nM). However, two variants of CAV1 exist: the full-length form, CAV1α (wild-type CAV1 or wtCAV1), and a truncated form, CAV1β. Only wtCAV1 has the Tyr-14 region at the N terminus. The precise cellular functions of CAV1 variants are unknown. We now show that CAV1 variants play distinct roles in paclitaxel-mediated cell death/survival. CAV1β expression is increased in paclitaxel-resistant cells when compared with sensitive cells. Expression of CAV1β in sensitive cells significantly reduces their responsiveness to paclitaxel. These activities reflect an essential role for Tyr-14 phosphorylation because wtCAV1 expression, but not a phosphorylation-deficient mutant (Y14F), inactivates BCL2 and BCLxL through activation of c-Jun N-terminal kinase (JNK). MCF-7 cells that express Y14F are resistant to paclitaxel and are resensitized by co-treatment with ABT-737, a BH3-mimetic small molecule inhibitor. Using structural homology modeling, we propose that phosphorylation on Tyr-14 enables a favorable conformation for proteins to bind to the CAV1 scaffolding domain. Thus, we highlight novel roles for CAV1 variants in cell death; wtCAV1 promotes cell death, whereas CAV1β promotes cell survival by preventing inactivation of BCL2 and BCLxL via JNK in paclitaxel-mediated apoptosis.


[Effects of thinning intensity on community stability of Quercus liaotungensis forest on Loess Plateau].
A sampling plot investigation was conducted on the Quercus liaotungensis forests on Loess Plateau, China under close-to-natural management thinning 13.4% (light thinning) and 30.0% (heavy thinning). Taking the un-thinned forest as the control, the population regeneration, woodland productivity, soil fertility, and species diversity of the forests after 5 years of thinning were studied, with the community stability evaluated by calculating the subordinate function values based on fuzzy comprehensive evaluation. Comparing with the control, the regeneration potential of the forests after light and heavy thinning promoted by 14.2% and 20.2%, arbor volume reduced by 9.0% and 23.8%, shrub biomass increased by 7.3% and 12.2%, and herb biomass increased by 10.5% and 31.6%, respectively. In addition, the soil fertility and species diversity indices were higher in thinning forests than in the control. The community stability showed the order of heavy thinning forest > light thinning forest > un-thinned forest, suggesting that the close-to-natural management thinning 30.0% was more suitable to the management of secondary Q. liaotungensis forest on Loess Plateau.


Evolutionarily stable size of a megagametophyte: evolution of tiny megagametophytes of angiosperms from large ones of gymnosperms.
To examine the factors favoring large megagametophytes of gymnosperms and tiny ones of angiosperms, a game model for seed production was developed in which megagametophytes growing in the same female parent compete for resources provided by the parent. In the model, megagametophytes may continue to grow until seed completion or may cease to grow at a certain time and regrow at pollination or fertilization. Autonomous abortion of unpollinated or unfertilized megagametophytes may occur either at pollination or fertilization. Those megagametophytes absorb a certain amount of resources before abortion, due to constraints in the signal process, in addition to the resources absorbed before pollination or fertilization. It was found that both growth habits can be the ESS: megagametophytes continue to grow without cessation and monopolize resources, such as gymnosperms, or cease to grow until fertilization to reduce the loss of resources due to autonomous abortion, such as angiosperms. The former and the latter are the ESS if the time interval between pollination and fertilization is long and short, respectively. Thus, the fertilization interval may be a critical factor selecting for large megagametophytes of gymnosperms or tiny ones of angiosperms.


Endothelial cell-specific ETB receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1.
Inactivation of endothelin B receptors (ETB), either through selective pharmacological antagonism or genetic mutation, increases the circulating concentration of endothelin-1 (ET-1), suggesting ETB plays an important role in clearance of this peptide. However, the cellular site of ETB-mediated clearance has not yet been determined. We have used a novel mouse model of endothelial cell-specific knockout (KO) of ETB (EC ETB(-/-)) to evaluate the relative contribution of EC-ETB to the clearance of ET-1. Phenotypic evidence of EC-specific ETB KO was confirmed by immunocytochemistry and autoradiography. Binding of the radiolabelled selective ETB ligand BQ3020 was significantly and selectively decreased in EC-rich tissues of EC ETB(-/-) mice, including the lung, liver, and kidney. By contrast, ETA binding was unaltered. RT-PCR confirmed equal expression of ET-1 in tissue from EC ETB(-/-) mice and controls, despite increased concentration of plasma ET-1 in EC ETB(-/-). Clearance of an intravenous bolus of [(125)I]ET-1 was impaired in EC ETB(-/-) mice. Pretreatment with the selective ETB antagonist A192621 impaired [(125)I]ET-1 clearance in control animals to a similar extent, but did not further impair clearance in EC ETB(-/-) mice. These studies suggest that EC-ETB are largely responsible for the clearance of ET-1 from the circulation.


Disordered Balance of T-Cell Subsets in Arterial Tertiary Lymphoid Organs in Immunoglobulin G4-Related Vascular Disease.
Arterial/aortic tertiary lymphoid organs (ATLOs), characterized by germinal centers, control local arterial immune responses. T follicular helper cells (Tfh), resident in germinal centers, regulate immunoglobulin production and germinal center development. They consist of Tfh1, Tfh2, and Tfh17 subsets. T follicular regulatory (Tfr) cells possess suppressive functions as regulatory T cells and migrate into germinal centers. Immunoglobulin G4 (IgG4)-related diseases manifest in vascular lesions as frequently formed inflammatory aneurysms (IgG4-related abdominal aortic aneurysm [IgG4-AAAs]). IgG4-AAAs contain several ATLOs. We performed whole-slide immunohistochemical image analysis in surgical specimens of IgG4-AAAs (n=21), non-IgG4-related inflammatory AAAs (n=17), atherosclerotic AAAs (n=10), and Takayasu arteritis (n=5). IgG4-AAA was characterized by numerous, large, irregular-shaped ATLOs, and higher numbers of Tfr and Tfh2 cells than Tfh1 cells were present compared with others. The morphologic abnormalities (in number, area, and form) of ATLOs in IgG4-AAAs and the increased number of Tfr cells are closely related to the activity of IgG4-related diseases. All T-cell subsets were more enriched within ATLOs than outside ATLOs. In particular, an increase in Tfr cells in IgG4-AAAs was associated with ATLO formation. Increased Tfh17 cells were found in Takayasu arteritis, and atherosclerotic AAA and non-IgG4-related inflammatory AAAs were characterized by increased Tfh1 cells. In the classification of vascular lesions, considering the imbalance in T-cell subsets, IgG4-AAA should be positioned as adventitial vasculitis with predominant Tfr and Tfh2 cells, accompanied by the abnormal appearance of ATLOs.


The nuclear Dbf2-related kinase COT1 and the mitogen-activated protein kinases MAK1 and MAK2 genetically interact to regulate filamentous growth, hyphal fusion and sexual development in Neurospora crassa.
Ndr kinases, such as Neurospora crassa COT1, are important for cell differentiation and polar morphogenesis, yet their input signals as well as their integration into a cellular signaling context are still elusive. Here, we identify the cot-1 suppressor gul-4 as mak-2 and show that mutants of the gul-4/mak-2 mitogen-activated protein (MAP) kinase pathway suppress cot-1 phenotypes along with a concomitant reduction in protein kinase A (PKA) activity. Furthermore, mak-2 pathway defects are partially overcome in a cot-1 background and are associated with increased MAK1 MAPK signaling. A comparative characterization of N. crassa MAPKs revealed that they act as three distinct modules during vegetative growth and asexual development. In addition, common functions of MAK1 and MAK2 signaling during maintenance of cell-wall integrity distinguished the two ERK-type pathways from the p38-type OS2 osmosensing pathway. In contrast to separate functions during vegetative growth, the concerted activity of the three MAPK pathways is essential for cell fusion and for the subsequent formation of multicellular structures that are required for sexual development. Taken together, our data indicate a functional link between COT1 and MAPK signaling in regulating filamentous growth, hyphal fusion, and sexual development.


Vasopeptidase Inhibition Prevents Endothelial Dysfunction of Resistance Arteries in Salt-Sensitive Hypertension in Comparison With Single ACE Inhibition.
-To determine whether natriuretic peptides in addition to the renin-angiotensin system are involved in functional and structural vascular changes in salt-sensitive hypertension, we compared equipotent hypotensive treatment with the dual neutral endopeptidase/ACE inhibitor omapatrilat (35 mg. kg(-1). d(-1)) or the ACE inhibitor captopril (100 mg. kg(-1). d(-1)). The reactivity and geometry of mesenteric resistance arteries from Dahl salt-sensitive rats were studied in vitro under perfused and pressurized conditions. Chronic salt administration increased systolic blood pressure by 57+/-4 mm Hg, whereas concentrations of atrial natriuretic peptide were reduced in heart and in plasma (P:<0.05). In addition, the medial cross-sectional area of small mesenteric arteries was increased and endothelium-dependent relaxation in response to acetylcholine and contraction in response to endothelin-1 were impaired in the mesenteric arteries of salt-sensitive rats on a high-salt diet (P:<0.05). Concomitant treatment with either omapatrilat or captopril reduced the increase in systolic blood pressure and hypertrophic remodeling to a similar degree (P:<0.05) but affected plasma and cardiac atrial natriuretic peptide levels differently (P:<0.05). In addition, omapatrilat normalized endothelium-dependent relaxations to a greater extent than captopril (P:<0.05). Furthermore, vasopeptidase inhibition increased cGMP levels compared with captopril (P:<0.05). Contractions to endothelin-1 were normalized by either antihypertensive drug. These results suggest that in the Dahl rat, with similar reductions in systolic blood pressure, omapatrilat is superior to captopril in preventing impaired endothelial function in small resistance arteries. Thus, vasopeptidase inhibition may have therapeutic advantages of the prevention of changes in vascular function and structure in salt-sensitive forms of hypertension.


Revised Standardized Equation for Hydrogen Gas Densities for Fuel Consumption Applications.
An equation for the density of hydrogen gas has been developed that agrees with the current standard to within 0.01 % from 220 K to 1000 K with pressures up to 70 MPa, to within 0.01 % from 255 K to 1000 K with pressures to 120 MPa, and to within 0.1 % from 200 K to 1000 K up to 200 MPa. The equation is a truncated virial-type equation based on pressure and temperature dependent terms. The density uncertainty for this equation is the same as the current standard and is estimated to be 0.04 % (combined uncertainty with a coverage factor of 2) between 250 K and 450 K for all pressures, and 0.1 % for lower temperatures. Comparisons are presented with experimental data and with the full equation of state.


The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system.
The Cbl family of proteins are evolutionarily conserved negative regulators of activated tyrosine kinase-coupled receptors. Antigen receptors are prominent targets of negative regulation by the Cbl family members, Cbl and Cbl-b, which proteins function as ubiquitin ligases. Cbl and Cbl-b contain substrate recognition domains that interact specifically with activated protein tyrosine kinases of the Src and Syk/ZAP-70 families. Cbl-mediated ubiquitination of these kinases leads to their degradation, resulting in attenuation of receptor signals. Cbl may also control activation-induced monoubiquitination of antigen receptors, thus facilitating their delivery to lysosomes for subsequent degradation. Finally, the interactions of Cbl proteins with downstream targets of tyrosine kinases, such as PI-3-kinase and Vav, could provide an additional mechanism to attenuate receptor signaling. By targeting multiple components of antigen receptor signaling for degradation, the Cbl protein family provides a critical mechanism to ensure an appropriate immune response. The hyperresponsiveness of Cbl(-/-) and Cbl-b(-/-) lymphocytes and the autoimmune phenotype of Cbl-b(-/-) mice lend strong support for this proposal. The ability to control early receptor signals through regulated protein degradation provides a novel paradigm of immunoregulation.


[Local irritation study with isepamicin].
Local irritative effects of isepamicin (HAPA-B) were studied using muscle and blood vessel of Japanese White rabbits. Muscle irritation experiment was carried out with a single dosage of 100 mg HAPA-B, 100 mg amikacin (AMK), saline, 0.75% acetic acid or 6.0% acetic acid administered into musculus sacrospinalis. Vascular irritation experiment was carried out by allowing HAPA-B to remain in a sealed section of vena retroauricularis for 3 minutes after injection. In result, the muscular irritative activity of HAPA-B was less severe than 0.75% acetic acid but more than saline, and almost equal activity to AMK was observed. The HAPA-B caused very slight inflammation while thrombus was not formed. The vascular irritative activity was very little.


The comparative effect of prolonged feeding with raw and heated soybean mean on the growth response, pancreatic enlargement and pancreatic enzymes of chicks.
Prolonged feeding of chicks with raw soybean meal as the main protein source in the diet resulted in growth inhibition, pancreas enlargement, and increased content of pancreatic proteolytic enzymes. The effect of feeding with raw soybean meal as compared to heated soybean meal upon total intestinal enzymatic activities in chicks was tested. The tendency of chicks to overcome the effects of raw soybean meal is expressed mainly by the increase of biosynthesis and secretion of proteolytic enzymes in the pancreas.


Involvement in sex work is associated with muscle dysmorphia symptomatology among a sample of Canadian adolescents and young adults.
The aim of this study was to investigate the association between lifetime sex work involvement and muscle dysmorphia symptomatology. Data from the Canadian Study of Adolescent Health Behaviours (N =912) were analysed. Multiple adjusted linear regression models were estimated with lifetime sex work involvement as the independent variable and muscle dysmorphia symptomatology, measured using the Muscle Dysmorphic Disorder Inventory, as the dependent variable. Among the sample, 3.7% of participants reported engaging in lifetime sex work. Significant associations were found between self-reported lifetime sex work and greater total muscle dysmorphia symptomatology (B =5.03, 95% CI 1.80, 8.26), greater Drive for Size symptomatology (B =2.36, 95% CI 0.74-3.97), and greater Functional Impairment symptomatology (B =2.11, 95% CI 0.54, 3.67), while adjusting for relevant sociodemographic variables. Findings from this study expand prior research that has documented poor mental health among individuals involved in sex work. Clinical and community health professionals should consider screening for muscle dysmorphia symptomatology among young people who have been involved in sex work.


LONG STANDING SCHIZOPHRENIA PRESENTING AS PARAPLEGIA IN NIGERIAN YOUTH.
Schizophrenia is a severe mental health disorder characterized by abnormality in patient perception, belief and cognition resulting in gross abnormal behaviour and deterioration in interpersonal relationship and occupational functioning with onset usually in adolescence and youth period. While it is common to observe distortion in the belief system and perceptual experiences and other oddities of behaviour, including amotivational syndrome, ambivalence, social withdrawal, catatonia among youth suffering from this severe mental disorder, presenting with neurological symptom of complete inability to walk despite the desire to do so is very uncommon. We aimed to present a case report of a Nigerian youth who presented with inability to walk without any neurological deficit and had normal brain MRI scan. This is to highlight the need to have high index of suspicion among practitioner especially in young person with sudden onset of "paraplegia". Mr X is a 30 years old single Lecturer who was brought into the hospital by relatives with two weeks history of sudden onset of inability to walk around and became bed bound. He graduated with first class in Mass Communication and commenced National Service as Lecturer when he started hearing voices discussing him and also believes that people want to kill. He became reclusive to self for about two years. No history of trauma to the head or hypertensive heart disease. He was earlier seen by a doctor who commenced him on carbamazepine and olanzapine but drugs adherent was poor and later completely abandon for unorthodox treatment. MRI Scan of the brain, FBC + diff, U & E and neurological examination were normal. He was commence on Risperdal and six weeks later into the treatment, he started ambulating about. While it may be rare, severe psychotic illness such as schizophrenia can result in complete inability to walk, mimicking neurological disorder. High index of suspicion with perseverance of treatment can resolve the patient illness and restore his social life.


Investigating a simplified method for noninvasive genetic sampling in East African mammals using silica dried scat swabs.
Swabbing scat has proved to be an effective noninvasive method to collect DNA from mammals in the field. Previously, this method has relied on preservative liquids or freezing to preserve the DNA collected on swabs. In this study, we determine the effectiveness of using silica to simply dry the swab in field as an alternative way to prevent DNA degredation. Four species were included in the study; reticulated giraffe, impala, fringe-eared oryx, and lion. Swabs were taken at multiple time points for giraffe and impala scat samples, with the lion and oryx sampled opportunistically. Mitochondrial DNA was successfully amplified and sequenced from scat swabs from all species; however, effectiveness varied between species, with 81.8% amplification success rate from swabs taken from impala scat compared to 25% amplification success rate in giraffe. This variation in success rate was overcome by taking multiple swabs, thus increasing the probability of a successful amplification. The true merit of this method is in its simplicity and cheapness; no preservative liquids were required to be brought into the field, at no stage in the 2 weeks of field sampling were samples frozen, and no commercial kits were used for DNA extraction.


Respiratory distress due to esophageal perforation caused by ball point ingestion.
A 15-month-old girl who developed respiratory distress which persisted for three days prior to admission demonstrated pleural effusion on the chest x-ray which was determined to be due to esophageal perforation caused by the ingestion of a ball point. A gastrotomy was performed to extract the ball point. A gastrostomy was performed and a chest tube was inserted. The esophagus was normal radiologically within one month. Foreign body ingestion may cause esophageal perforation in childhood. If it goes unnoticed and a diagnosis is delayed, there is danger of the more hazardous development of mediastinitis. It is important that a child with respiratory distress also be evaluated for esophageal foreign body ingestion.


Adhesive Tape Microfluidics with an Autofocusing Module That Incorporates CRISPR Interference: Applications to Long-Term Bacterial Antibiotic Studies.
The ability to study bacteria at the single cell level has advanced our insights into microbial physiology and genetics in ways not attainable by studying large populations using more traditional culturing methods. To improve methods to characterize bacteria at the cellular level, we developed a new microfluidic platform that enables cells to be exposed to metabolites in a gradient of concentrations. By designing low-cost, three-dimensional devices with adhesive tapes and tailoring them for bacterial imaging, we avoided the complexities of silicon and polymeric microfabrication. The incorporation of an agarose membrane as the resting substrate, along with a temperature-controlled environmental chamber, allows the culturing of bacterial cells for over 10 h under stable growth or inhibition conditions. Incorporation of an autofocusing module helped the uninterrupted, high-resolution observation of bacteria at the single-cell and at low density population levels. We used the microfluidic platform to record morphological changes in Escherichia coli during ampicillin exposure and to quantify the minimum inhibitory concentration of the antibiotic. We further demonstrated the potential of finely-tuned, incremental gene regulation in a concentration gradient utilizing CRISPR interference (CRISPRi). These low-cost engineering tools, when implemented in combination with genetic approaches such as CRISPRi, should prove useful to uncover new genetic determinants of antibiotic susceptibility and evaluate the long-term effectiveness of antibiotics in bacterial cultures.


Mobile Charging Strategy for Wireless Rechargeable Sensor Networks.
In a wireless sensor network, the sensing and data transmission for sensors will cause energy depletion, which will lead to the inability to complete the tasks. To solve this problem, wireless rechargeable sensor networks (WRSNs) have been developed to extend the lifetime of the entire network. In WRSNs, a mobile charging robot (MR) is responsible for wireless charging each sensor battery and collecting sensory data from the sensor simultaneously. Thereby, MR needs to traverse along a designed path for all sensors in the WRSNs. In this paper, dual-side charging strategies are proposed for MR traversal planning, which minimize the MR traversal path length, energy consumption, and completion time. Based on MR dual-side charging, neighboring sensors in both sides of a designated path can be wirelessly charged by MR and sensory data sent to MR simultaneously. The constructed path is based on the power diagram according to the remaining power of sensors and distances among sensors in a WRSN. While the power diagram is built, charging strategies with dual-side charging capability are determined accordingly. In addition, a clustering-based approach is proposed to improve minimizing MR moving total distance, saving charging energy and total completion time in a round. Moreover, integrated strategies that apply a clustering-based approach on the dual-side charging strategies are presented in WRSNs. The simulation results show that, no matter with or without clustering, the performances of proposed strategies outperform the baseline strategies in three respects, energy saving, total distance reduced, and completion time reduced for MR in WSRNs.


Cost effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer.
To assess the cost-effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer. An analytical decision model was developed to determine the cost-effectiveness of chemohormonal therapy versus androgen deprivation therapy alone in patients with metastatic hormone-sensitive prostate cancer and patients with non-metastatic high-risk prostate cancer. The cost-effectiveness in metastatic patients with a high-volume disease was assessed separately. The model used data from randomized clinical trials and drug acquisition costs in Brazil. In addition, the costs of post-progression therapies have been included in this model. The benefits to health are expressed as the quality-adjusted life-years, and the incremental cost-effectiveness ratios were calculated. Chemohormonal therapy may be associated with improved quality-adjusted life-years for all patient. The improvement was more than six times greater for patients with high-volume metastatic disease. In these patients, the incremental cost-effectiveness ratios were up to 74% lower than the incremental cost-effectiveness ratios of patients with non-metastatic disease. Chemohormonal therapy has been more cost-effective in patients with high-volume metastatic disease.


Robotic Transrectal Ultrasound Guided Prostate Biopsy.
We present a robot-assisted approach for transrectal ultrasound (TRUS) guided prostate biopsy. The robot is a hands-free probe manipulator that moves the probe with the same 4 DoF that are used manually. Software was developed for three-dimensional (3-D) imaging, biopsy planning, robot control, and navigation. Methods to minimize the deformation of the prostate caused by the probe at 3-D imaging and needle targeting were developed to reduce biopsy targeting errors. We also present a prostate coordinate system (PCS). The PCS helps defining a systematic biopsy plan without the need for prostate segmentation. Comprehensive tests were performed, including two bench tests, one imaging test, two in vitro targeting tests, and an IRB-approved clinical trial on five patients. Preclinical tests showed that image-based needle targeting can be accomplished with accuracy on the order of 1 mm. Prostate biopsy can be accomplished with minimal TRUS pressure on the gland and submillimetric prostate deformations. All five clinical cases were successful with an average procedure time of 13 min and millimeter targeting accuracy. Hands-free TRUS operation, transrectal TRUS guided prostate biopsy with minimal prostate deformations, and the PCS-based biopsy plan are novel methods. Robot-assisted prostate biopsy is safe and feasible. Accurate needle targeting has the potential to increase the detection of clinically significant prostate cancer.


Association of the eukaryotic vaginal virome with prophylactic antibiotic exposure and reproductive outcomes in a subfertile population undergoing in vitro fertilisation: a prospective exploratory study.
The objective of this study was to use high-throughput sequencing to describe the vaginal eukaryotic DNA virome in patients undergoing in vitro fertilisation (IVF) to examine associations between the vaginal virome, antibiotic exposure and IVF outcomes. Prospective exploratory study. Single academic fertility centre. Subfertile women age 18-43 years undergoing their first IVF cycle with a fresh embryo transfer. The primary exposure was prophylactic azithromycin or no azithromycin before IVF. A mid-vaginal swab was obtained at the time of embryo transfer for virome analysis. The primary outcomes compared between exposure groups were characteristics of vaginal virome and clinical pregnancy rates. Secondary outcomes were virome associations with number of oocytes retrieved, number of blastocysts and implantation rate. Twenty-six women contributed a vaginal swab before embryo transfer. There were no significant differences in IVF outcomes between azithromycin groups. There was no association between viral diversity and clinical pregnancy overall. A higher diversity of herpesviruses and α-papillomaviruses was observed in samples from the azithromycin-treated group compared with the no azithromycin group (P = 0.04). In women that received azithromycin, viral diversity was higher in the group that did not achieve clinical pregnancy compared with those who did (P = 0.06). We demonstrate that the vaginal eukaryotic virome in women undergoing IVF is associated with antibiotic exposure. Additionally, we demonstrate an inverse trend between viral diversity and pregnancy, with a higher number of viruses detected associated with failure to achieve clinical pregnancy in the azithromycin group. Higher viral diversity is associated with prophylactic antibiotic exposure in subfertile women undergoing IVF.


Involvement of plasma membrane glycoproteins in the contact-dependent inhibition of growth of human fibroblasts.
The human embryonal lung fibroblasts used in this study showed a pronounced inhibition of growth when reaching a critical cell density. This effect has been mimicked by the addition of glutaraldehyde-fixed human fibroblasts to sparsely seeded growing cells. Inhibition of growth was not observed when glutaraldehyde-fixed cells were pretreated with galactosidase or with galactose-specific lectins, or when glutaraldehyde-fixed human or rabbit erythrocytes were added to the proliferating fibroblasts. In addition, glutaraldehyde-fixed mitotic cells were without effect on the proliferation, while cells prepared from sparse culture had lesser potency than cells prepared from confluent cultures. Plasma membranes, isolated from cells of confluent cultures, when added to growing cultures of human fibroblasts inhibited DNA synthesis in a concentration-dependent manner. On the other hand, plasma membranes isolated from sparsely seeded cells had only minor inhibitory potency. When the plasma membranes were isolated from cells treated previously with tunicamycin, an antibiotic which inhibits the synthesis of the oligosaccharide portion of asparagine-linked glycoproteins, the inhibitory effect was abolished. The same effect was observed when plasma membranes were pretreated with galactosidase. These data indicate that the growth of cells in vitro is regulated by specific cell-cell contacts. They also show that one of the molecular reactants in this process are membrane glycoproteins with asparagine-linked oligosaccharides.


Phenacetin and acetaminophen metabolism in the isolated perfused rat liver. Precursor concentration influences the selection of kinetic parameters to assess hypoxic impairment.
Subnormal oxygen concentrations affect a host of cellular functions and can exist under normal or pathological conditions. The present study examined the effects of hypoxia on phenacetin O-deethylation by the mixed-function oxidase system and the subsequent sulfation and glucuronidation of the generated metabolite acetaminophen, compared to hypoxic alterations in conjugation of administered acetaminophen, in isolated perfused rat livers. A recirculating perfusion system containing either 20% (normoxic conditions) or 2.5% (hypoxic conditions) donor rat blood delivered 4.46 and 1.47 mumol/min/g liver oxygen, respectively, resulting in a 44% reduction in oxygen consumption during hypoxia. The total hepatic clearance of phenacetin was diminished significantly during hypoxia, due to a 60% decrease in the formation clearance of acetaminophen. Hypoxia did not influence significantly the total hepatic clearance of either administered or generated acetaminophen. Although the formation clearance for acetaminophen sulfate (AS) remained unchanged, the Vmax for sulfate formation was diminished 35%. The formation clearance (mean +/- SD; N = 4/group) of acetaminophen glucuronide (AG) was greater from administered compared to generated acetaminophen during normoxia (0.47 +/- 0.15 vs. 0.22 +/- 0.06 ml/min, p less than 0.05), and was decreased 2- to 3-fold during hypoxia (0.14 +/- 0.08 vs. 0.11 +/- 0.07 ml/min). Hypoxic conditions did not affect differentially the time lag for the appearance of AG in perfusate, and did not appear to alter the diffusional barrier for AS and AG from perfusate into the hepatocyte.


Interrater reliability of Sensory Integration and Praxis Tests (SIPT) score interpretation.
This study examined interrater reliability of score interpretation on the Sensory Integration and Praxis Tests (SIPT). Using SIPT scores of two complex cases, 20 trained participants independently rated each case for presence of sensory integrative dysfunction and for relevance of specific patterns of dysfunction. They also provided comments to justify their ratings. Agreement on the presence of sensory integrative dysfunction was 70% for Case A and 100% for Case B. Reliability was more variable for dysfunctional pattern ratings, ranging from 50% to 100% agreement for Cases A and B, respectively. Participants consistently appeared to use configural decision-making strategies to guide their ratings. Interrater reliability was moderate to high for interpretation of the presence of sensory integrative dysfunction using SIPT scores. Less agreement was apparent regarding specific patterns of dysfunction. Results suggest that additional clinical information, such as clinical observations and case history, may be needed to make reliable distinctions among dysfunctional patterns.


Prediction of the Ideal Implant Size Using 3-Dimensional Healthy Breast Volume in Unilateral Direct-to-Implant Breast Reconstruction.
Background and objectives: There is no consensus regarding accurate methods for assessing the size of the implant required for achieving symmetry in direct-to-implant (DTI) breast reconstruction. The purpose of this study was to determine whether the ideal implant size could be estimated using 3D breast volume or mastectomy specimen weight, and to compare prediction performances between the two variables. Materials and Methods: Patients who underwent immediate DTI breast reconstruction from August 2017 to April 2020 were included in this study. Breast volumes were measured using 3D surface imaging preoperatively and at postoperative three months. Ideal implant size was calculated by correcting the used implant volume by the observed postoperative asymmetry in 3D surface imaging. Prediction models using mastectomy weight or 3D volume were made to predict the ideal implant volume. The prediction performance was compared between the models. Results: A total of 56 patients were included in the analysis. In correlation analysis, the volume of the implant used was significantly correlated with the mastectomy specimen weight (R2 = 0.810) and the healthy breast volume (R2 = 0.880). The mean ideal implant volume was 278 ± 123 cc. The prediction model was developed using the healthy breast volume: Implant volume (cc) = healthy breast volume × 0.78 + 26 cc (R2 = 0.900). The prediction model for the ideal implant size using the 3D volume showed better prediction performance than that of using the mastectomy specimen weight (R2 = 0.900 vs 0.759, p < 0.001). Conclusions: The 3D volume of the healthy breast is a more reliable predictor than mastectomy specimen weight to estimate the ideal implant size. The estimation formula obtained in this study may assist in the selection of the ideal implant size in unilateral DTI breast reconstruction.


Psychological Distress and Emotional Expression on Facebook.
Social network sites (SNS) are a novel social environment for college students with psychological distress to connect with their peers, but the nature and effects of these interactions are not well understood. This study reports findings from a Facebook study among 238 college students reporting nonspecific psychological distress using the K-6 scale. Behavioral data included Facebook status updates containing affect words written by participants within the past 60 days and the number of responses (comments and likes) each update received. The updates were also coded for depression symptoms. Self-report data included participants' self-presentational concerns, the affective valence of each post, effects of responses on mood, and satisfaction with the responses to and outcome of each status update. Higher psychological distress was associated with displaying depression language on Facebook, with higher self-presentational concerns, and with less satisfaction with audiences' responses and less overall satisfaction with the outcome of the interaction. These results offer a unique glimpse into the social world of college students with psychological distress through their everyday use of Facebook, and how the interplay of this novel environment and students' mental health impacts their social behaviors and interaction meaning-making on Facebook.


[Tuberculosis of the urinary bladder: diagnosis and treatment].
Tuberculosis of the urinary bladder (UB) is registered in 10-45.6% patients with urogenital tuberculosis. It is a severe incapacitating complication of kidney tuberculosis which significantly lowers quality of life. The results of the standard therapy of 76 patients with tuberculous cystitis are analysed. UB tuberculosis is diagnosed more often in women, outcomes of their treatment are worse. Twenty six patients with UB tuberculosis at the stage of overactive bladder received polychemotherapy and adjuvant trospium. After 3 months urination frequency decreased 4.3 times, on the average; UB volume increased 4.7 times, on the average. Complications were not registered.


Isolation of Live Immune Cells from the Tumor Microenvironment by FACS.
Isolation of live cells from the tumor microenvironment (TME) has represented a challenge, particularly from metastatic nodules that need to be identified within the entire metastatic tissue. Cherry-niche, an in vivo labelling technique, allows the isolation of all the different cell populations in the TME without needing to visually locate the metastatic cancer cell colonies. Therefore, neighboring TME cells can be isolated even from the early stages of cancer cell seeding and colonization in the metastatic tissue. Here, we show how to use Cherry-niche to identify and isolate neutrophils from the lung metastatic niche. We also provide examples of downstream analyses to characterize freshly isolated neutrophils ex vivo, such as Giemsa staining, reactive oxygen species (ROS) detection, and phagocytosis assays. Similar strategies can be used to isolate other immune and non-immune cells from the metastatic TME.


Quality control for community-based sea-ice model development.
A new collaborative organization for sea-ice model development, the CICE Consortium, has devised quality control procedures to maintain the integrity of its numerical codes' physical representations, enabling broad participation from the scientific community in the Consortium's open software development environment. Using output from five coupled and uncoupled configurations of the Los Alamos Sea Ice Model, CICE, we formulate quality control methods that exploit common statistical properties of sea-ice thickness, and test for significant changes in model results in a computationally efficient manner. New additions and changes to CICE are graded into four categories, ranging from bit-for-bit amendments to significant, answer-changing upgrades. These modifications are assessed using criteria that account for the high level of autocorrelation in sea-ice time series, along with a quadratic skill metric that searches for hemispheric changes in model answers across an array of different CICE configurations. These metrics also provide objective guidance for assessing new physical representations and code functionality.This article is part of the theme issue 'Modelling of sea-ice phenomena'.


Effects of greater occipital nerve block with local anesthetic and triamcinolone for treatment of medication overuse headache: an open-label, parallel, randomized, controlled clinical trial.
There is a paucity of evidence and consensus on exactly how to carry out the detoxification process. To examine the effect of a greater occipital nerve block (GONB) in the detoxification process, we conducted an open-label, parallel, randomized, controlled clinical trial. In order to conduct this study, 54 medication-overuse headache (MOH) patients were recruited and allocated randomly to group A (n = 27) or B (n = 27). In both groups, patients underwent detoxification processes without any acute migraine medication or analgesics. During the run-in period, all patients in both groups received the same education, managed by a neurologist and nutritionist. All patients were offered maximally 300 mL of promethazine syrup (5 mg/5 mL) to be taken 10 mg every 8 h during the first 10 days of the study. A 2-mL syringe containing 1 mL of lidocaine 2% and 1 mL of triamcinolone 40 mg/mL was prepared for each patient of group A for conducting GONB. Characteristics of headache attacks, including headache severity, frequency, and duration, were assessed at baseline and after 3 months of intervention. Twenty-six patients in group A (96.3%) and twenty-three in group B (85.2%) completed detoxification, and were thus cured of MOH (P = 0.351). The present study revealed that GONB with local anesthetic and triamcinolone significantly improved the characteristics of headache, including frequency (- 13.66 in group A and - 7.55 in group B), duration (- 7.92 in group A and - 5.88 in group B), and severity (- 3.44 in group A vs. - 1.33 in group B) in group A compared to control (all P value < 0.05). Although both detoxification programs were effective, detoxification with GONB resulted in better outcomes. Iranian Registry of Clinical Trials (registration number; IRCT20150906023922N2).