Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults.
Melanocortin 4 receptor (MC4R) has a major role in energy homeostasis. The rs17782313 polymorphism, mapped 188 kb downstream from MC4R, has been associated with satiety, higher body mass index (BMI) and total calorie intake in adults. To assess the association of rs17782313 with gastric functions, satiation, or satiety, we studied 178 predominantly Caucasian overweight and obese people: 120 females, 58 males; mean BMI 33.4 ± 5.3 kg/m(2) (SD); age 37.7 ± 11.2 years. Quantitative traits assessed were gastric emptying (GE) of solids and liquids; fasting and postprandial gastric volume; satiation by maximum tolerated volume and 4 symptoms by 100-mm visual analog scales (VAS); and satiety by ad libitum buffet meal. Associations of genotype and quantitative traits were assessed by analysis of covariance (using gender and BMI as covariates), based on a dominant [TC (n = 72) - CC (n = 12) vs. TT (n = 94)] genetic model. rs17782313(C) was associated with postprandial satiation symptoms (median Δ total VAS 26.5 mm, p = 0.036), reduced proportion of solid GE at 2 h (median Δ 6.7 %, p = 0.008) and 4 h (median Δ 3.2 %, p = 0.006), and longer t ½ (median Δ 6 min, p = 0.034). Associations of rs17782313 with obesity may be explained by reduced satiation and GE. The role of MC4R mechanisms in satiation and gastric function deserves further study.


Edge-forming methods for color image zooming.
This paper introduces edge-forming schemes for image zooming of color images by general magnification factors. In order to remove/reduce artifacts arising in image interpolation, such as image blur and the checkerboard effect, an edge-forming method is suggested to be applied as a postprocess of standard interpolation methods. The method is based on nonconvex nonlinear partial differential equations. The equations are carefully discretized, incorporating numerical schemes of anisotropic diffusion, to be able to form reliable edges satisfactorily. The alternating direction implicit (ADI) method is employed for an efficient simulation of the model. It has been numerically verified that the resulting algorithm can form clear edges in 2 to 3 ADI iterations. Various results are given to show th eeffectiveness and reliability of the algorithm.


Effect of one-rescuer compression/ventilation ratios on cardiopulmonary resuscitation in infant, pediatric, and adult manikins.
Optimal chest compression to ventilation ratio (C:V) for one-rescuer cardiopulmonary resuscitation (CPR) is not known, with current American Heart Association recommendations 3:1 for newborns, 5:1 for children, and 15:2 for adults. C:V ratios influence effectiveness of CPR, but memorizing different ratios is educationally cumbersome. We hypothesized that a 10:2 ratio might provide adequate universal application for all age arrest victims. Clinical study. Tertiary care children's hospital. Thirty-five health care providers. Thirty-five health care providers performed 5-min epochs of one-rescuer CPR at C:V ratios of 3:1, 5:1, 10:2, and 15:2 in random order on infant, pediatric, and adult manikins. Compressions were paced at 100/min by metronome. The number of effective compressions and ventilations delivered per minute was recorded by a trained basic life support instructor. Subjective assessments of fatigue (self-report) and exertion (change in rescuer pulse rate compared with baseline) were assessed. Analysis was by repeated measures analysis of variance and paired Student's t-test. Effective infant compressions per minute did not differ by C:V ratio, but ventilations per minute were greater at 3:1 vs. 5:1, 10:2, and 15:2 (p < .05). Effective pediatric compressions per minute were less at 3:1 vs. 5:1, 10:2, and 15:2 (p < .05) and not different between 5:1, 10:2, and 15:2 ratios. Effective pediatric ventilations per minute were greater at 3:1 than all other ratios and both 5:1 and 10:2 were >15:2 (p < .05). Effective adult compressions per minute were progressively greater with 3:1 vs. 5:1 vs. 10:2 vs. 15:2 (p < .05). Self-efficacy was assessed, and rescuers always subjectively rated 10:2 and 15:2 ratios as easier than 5:1 or 3:1 ratios for all manikins. Rescuer pulse change (exertion) was greater after pediatric and adult vs. infant CPR (p < .05), with no significant difference by C:V ratio. C:V ratio and manikin size have a significant influence on the number of effective compressions and ventilations delivered during ideal, metronome-paced, one-rescuer CPR. Low ratios of 3:1, 5:1, and 10:2 favor ventilation, and high ratios of 15:2 favor compression, especially in adult manikins. Rescuers subjectively preferred C:V ratios of 10:2 and 15:2 over 3:1 or 5:1. Infant CPR caused less exertion and subjective fatigue than pediatric or adult CPR technique, without significant difference by C:V ratio. We speculate that a universal 10:2 C:V ratio for one-rescuer layperson CPR is physiologically reasonable but warrants further study with particular attention to educational value and technique retention.


Involvement of the Drosophila taurine/aspartate transporter dEAAT2 in selective olfactory and gustatory perceptions.
Excitatory amino acid transporters (EAATs) are membrane proteins involved in the uptake of neurotransmitter amino acids in the nervous system. The Drosophila dEAAT2 gene was previously described to encode a taurine/aspartate transporter. To analyze further the expression pattern and physiological function of this protein, we generated transgenic flies containing either the dEAAT2 promoter region fused to GAL4 (dEAAT2-GAL4) or a transgene allowing expression of a dEAAT2::GFP fusion protein (UAS-dEAAT2::GFP). We observed that dEAAT2-GAL4 expresses green fluorescent protein (GFP) in neurons in central and peripheral structures of third-instar larvae and adult flies. Labeled neurons were found in olfactory and gustatory pathways, in which dEAAT2::GFP was detected from the dendrites of the sensory neurons up to the first- and second-order centers. dEAAT2-GAL4 is also expressed in mechanosensory neurons. We found that a viable piggyBac insertion strain disrupts dEAAT2 expression. This mutant appears morphologically normal and presents no locomotor or phototaxis impairments; however, its brain taurine level is significantly reduced compared with that of wild-type flies. The dEAAT2 mutant showed decreased avoidance behavior in the presence of high concentration of propionic acid compared with wild-type flies, but no modification of the avoidance response to benzaldehyde. In gustatory tests, both mutant and control flies were normally attracted to sucrose; however, the dEAAT2 mutant presented a higher salt sensitivity, being repulsed by low and high salt concentrations. Therefore, we conclude that dEAAT2 does function as a taurine transporter in vivo and that this protein is physiologically required for the sensory perception of specific environmental molecules.


Multiple Origins of Secretagogin Expressing Cortical GABAergic Neuron Precursors in the Early Human Fetal Telencephalon.
Secretagogin (SCGN) which acts as a calcium signaling sensor, has previously been shown to be expressed by a substantial population of cortical GABAergic neurons at mid-gestation in humans but not in mice. The present study traced SCGN expression in cortical GABAergic neurons in human fetal forebrain from earlier stages than previously studied. Multiple potential origins of SCGN-expressing neurons were identified in the caudal ganglionic eminence (CGE) lateral ganglionic eminence (LGE) septum and preoptic area; these cells largely co-expressed SP8 but not the medial ganglionic eminence marker LHX6. They followed various migration routes to reach their target regions in the neocortex, insular and olfactory cortex (OC) and olfactory bulbs. A robust increase in the number of SCGN-expressing GABAergic cortical neurons was observed in the midgestational period; 58% of DLX2+ neurons expressed SCGN in the cortical wall at 19 post-conceptional weeks (PCW), a higher proportion than expressed calretinin, a marker for GABAergic neurons of LGE/CGE origin. Furthermore, although most SCGN+ neurons co-expressed calretinin in the cortical plate (CP) and deeper layers, in the marginal zone (MZ) SCGN+ and calretinin+ cells formed separate populations. In the adult mouse, it has previously been shown that in the rostral migratory stream (RMS), SCGN, annexin V (ANXA5), and matrix metalloprotease 2 (MMP2) are co-expressed forming a functioning complex that exocytoses MMP2 in response to calcium. In the present study, ANXA5 showed widespread expression throughout the cortical wall, although MMP2 expression was very largely limited to the CP. We found co-expression of these proteins in some SCGN+ neurons in the subventricular zones (SVZ) suggesting a limited role for these cells in remodeling the extracellular matrix, perhaps during cell migration.


Prerandomization: an alternative to classic randomization. The effects on recruitment in a controlled trial of arthroscopy for osteoarthrosis of the knee.
Possibly the greatest threat to the success of a randomized clinical trial is the inability to recruit an adequate number of subjects. Concern that the randomized clinical trial will adversely affect the physician-patient relationship is the most common reason for physicians' reluctance to enroll patients in such trials. We report a modification of a prerandomized design, first described by Zelen, which was implemented in a randomized clinical trial of arthroscopy for patients who had osteoarthrosis of the knee. The method was associated with a sixfold increase in the rate of accrual of patients as compared with the use of a classic randomization trial. We propose the design as a potential solution to the problem of recruitment of subjects, particularly for clinical studies.


The obesity paradox: an endocrine perspective.
Obesity is a growing epidemic both in Australia and worldwide. Being overweight or obese is known to be adversely associated with multiple cardiovascular risk factors, such as type 2 diabetes mellitus, lipid disorders and hypertension. Despite the adverse impact of overweight and obesity, recent observational studies have suggested that in some overweight and obese individuals with established chronic disease, there is a survival advantage that is paradoxically better than individuals of normal weight. A burgeoning area of interest is the existence of this paradox in chronic endocrine disorders, especially with respect to osteoporosis and type 2 diabetes mellitus, as well as the latter's chronic complications, chronic kidney disease and coronary artery disease. In this article, we review the postulated mechanisms and latest evidence concerning the obesity paradox, with a focus on endocrine-related diseases. We discuss confounders and biases that exist in observational studies from which the paradox has been described and highlight that, despite the observed paradox, substantial literature exists supporting the benefits of weight reduction in obesity.


Anti-vitronectin antibodies enhance anti-Thy-1-induced proteinuria in PVG/c, but not in Wistar rats.
Injection of rats with mouse monoclonal IgG2a anti-Thy1.1 antibodies (ER4G) results in rapid development of proteinuria in Wistar rats, reaching average values of 160 mg/24 h on day 3 after antibody administration. In contrast, no overt proteinuria was observed in PVG/c+ rats (maximum, 40 mg/24 h on day 3). This study investigates whether differences in the inactivation of C5b-9 complexes in the glomerulus by complement inhibitors are responsible for the differences in proteinuria between the two rat strains. Regardless of the presence of proteinuria, an increased expression of Crry by mesangial cells (MC) was observed within 24 h after injection of ER4G in both Wistar and PVG/c+ rats. Double-label immunofluorescence using goat anti-mouse Ig antibodies demonstrated an expression of Crry exclusively on MC. Furthermore, Crry colocalized with C5b-9 complexes on MC, as detected by a monoclonal antibody against the rat C5b-9 neo-antigen. In PVG/c+ rats, C5b-9 complexes persisted in the mesangial area for at least 7 d and colocalized immediately (within 1 h) and homogeneously with vitronectin. However, in proteinuric Wistar rats, C5b-9 complexes disappeared from the glomerular mesangium within 6 d. In these rats, mesangial colocalization of C5b-9 with vitronectin could only occasionally be detected. Pretreatment of PVG/c+ rats with antibodies against vitronectin, followed by administration of ER4G, resulted in the immediate development of proteinuria (maximum, 119 mg/24 h on day 3; P < 0.05), whereas Wistar rats did not become more proteinuric. This study provides evidence that differences in susceptibility of PVG/c+ and Wistar rats to complement-mediated damage of the glomerulus may be related to the degree of inactivation of C5b-9 complexes by complement regulatory factors.


Use of synthetic peptides to represent surface-exposed epitopes defined by neutralizing dengue complex- and flavivirus group-reactive monoclonal antibodies on the native dengue type-2 virus envelope glycoprotein.
The reactions of neutralizing monoclonal antibodies (mAbs) that defined dengue virus (DENV) complex, flavivirus subgroup or group neutralizing epitopes were tested against synthetic peptide sequences from domains I, II and III of the envelope (E) glycoproteins of different DENV-2 genotypes/strains. The DENV complex-reactive mAb identified the surface-exposed 304-GKFKV/IVKEIA-313 peptides and the DENV complex-conserved 393-KKGSSIGQ/KM-401 peptides in domain III, which were located adjacently in the native glycoprotein. Both flavivirus group-reactive mAbs reacted most strongly with fusion sequence peptides from domain II when they contained a cysteine (C) by glycine (G) substitution (underlined) (101-WGNGGGLFG-109) to represent the native rotated C side chain. The 393-401 sequence represents a newly identified epitope, present as a highly flexible coil located between the 385 and 393 cell-binding sequence and the 401 and 413 sequence involved in the E glycoprotein homo-trimer formation. The 101-109 sequence containing 105-C by G substitution and the 393-401 sequence are good candidates for diagnostic assays and cross-protection experiments.


Impact of wearing a surgical facemask during exercise on dyspnea in patients with chronic pulmonary infections: A randomized crossover study.
Wearing facemasks in public is effective in preventing viral transmission. However, no study has evaluated the impact of wearing facemasks during exercise on dyspnea in patients with chronic pulmonary infections from multifaceted aspects, including sensory qualities and emotional responses. The aim of this study was to evaluate facemask-related dyspnea during exercise in this patient population. We conducted a randomized crossover study involving adult patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) or bronchiectasis who participated in exercise sessions, both with (mask-on) and without (mask-off) surgical facemasks. The sensory and emotional dimensions of dyspnea during each exercise session were assessed using the Multidimensional Dyspnea Profile. Statistical analyses were performed to identify factors associated with worsening scores for each dimension. Thirty-four patients (mean age [standard deviation]: 71.6 [8.6] years) were included in the analysis. The median [interquartile range] total scores for the sensory and emotional dimensions of dyspnea were 3.5 [1, 9.5] (mask-off) vs. 10 [5.5, 23.8] (mask-on) (P < 0.001) and 0 [0, 5] (mask-off) vs. 3 [0.8, 10.3] (mask-on) (P = 0.115), respectively. "Air hunger" was the primary sensory descriptor of mask-related dyspnea. Vital capacity (VC) < 80% of the predicted value was a significant risk factor for worsening sensory dimension scores when wearing masks (odds ratio [95% confidence interval]: 5.5 [1.16-26.1], P = 0.038). The findings of this study indicate that patients with NTM-PD or bronchiectasis, particularly those with VC <80% of the predicted value, are likely to experience the sensory dimension of dyspnea during exercise while wearing surgical facemasks.


GATA2 gene analysis in several forms of hematological malignancies including familial aggregations.
The genetic predisposition to familial hematological malignancies has been previously reported highlighting inherited gene mutations. Several genes have been reported but genetic basis remains not well defined. In this study, we extended our investigation to a potential candidate GATA2 gene which was analyzed by direct sequencing in 119 cases including familial aggregations with a variety of hematological malignancies and sporadic acute leukemia belonging to Tunisian and French populations. We reported a deleterious p.Arg396Gln GATA2 mutation in one patient diagnosed with both sporadic acute myeloid leukemia (AML) and breast cancer. We also reported several GATA2 variations in familial cases. The absence of deleterious mutations in this large cohort of familial aggregations of hematological malignancies may strengthen the hypothesis that GATA2 mutations are an important predisposing factor, although as a secondary genetic event, required for the development of overt malignant disease.


Heat stress leads to superoxide formation in Bacillus cereus detected using the fluorescent probe MitoSOX.
Bacillus cereus is a food-borne human pathogen and food spoilage organism. Spores and vegetative cells of B. cereus can be found almost everywhere and therefore often end up in food processing equipment and food products. To remove spores and vegetative cells from food or equipment, harsh treatments such as high temperatures are applied. The heat stress response of B. cereus and other organisms has been studied and it has been shown that reactive oxygen species may be involved in inactivating the bacterial cells. Using a novel approach with the fluorescent probe MitoSOX, the formation of superoxide in B. cereus cells upon exposure to heat has been confirmed. MitoSOX can be used in combination with other probes, including, SYTOX green, CYTO 9, and CFDA, showing superoxide formation in combination with damaged cell membranes, intact cell membranes, and esterase activity in cells with intact membranes, respectively. MitoSOX in combination with flow cytometry-assisted sorting showed three distinct populations, a low fluorescent population that was still viable, a highly fluorescent population that could not be recovered on agar plates, and a low fluorescent non-viable population that appeared after prolonged exposure to heat. This third population may include dead cells where MitoSOX binds to DNA without reacting with superoxide. Superoxide formation during exposure to lethal temperatures by B. cereus shows that superoxide plays a role in bacterial cell death and its generation may thus contribute to the efficiency of food preservation conditions.


Usage of automation tools in systematic reviews.
Systematic reviews are a cornerstone of today's evidence-informed decision making. With the rapid expansion of questions to be addressed and scientific information produced, there is a growing workload on reviewers, making the current practice unsustainable without the aid of automation tools. While many automation tools have been developed and are available, uptake seems to be lagging. For this reason, we set out to investigate the current level of uptake and what the potential barriers and facilitators are for the adoption of automation tools in systematic reviews. We deployed surveys among systematic reviewers that gathered information on tool uptake, demographics, systematic review characteristics, and barriers and facilitators for uptake. Systematic reviewers from multiple domains were targeted during recruitment; however, responders were predominantly from the biomedical sciences. We found that automation tools are currently not widely used among the participants. When tools are used, participants mostly learn about them from their environment, for example, through colleagues, peers, or organization. Tools are often chosen on the basis of user experience, either by own experience or from colleagues or peers. Lastly, licensing, steep learning curve, lack of support, and mismatch to workflow are often reported by participants as relevant barriers. While conclusions can only be drawn for the biomedical field, our work provides evidence and confirms the conclusions and recommendations of previous work, which was based on expert opinions. Furthermore, our study highlights the importance that organizations and best practices in a field can have for the uptake of automation tools for systematic reviews.


Exploring how workplace and social policies relate to caregivers' financial strain.
Informal caregiving is a critical component of the US long-term care system, but can have significant negative impacts on caregiver employment, finances, and well-being. An online survey of Colorado caregivers was piloted in 2016-17 to explore whether workplace and social policies such as access to paid family leave and public health insurance can buffer the negative financial impacts of caregiving and help caregivers to remain in the workforce. Using standardized measures, the survey assessed caregivers' employment and financial status, well-being (physical and mental health, caregiver strain, benefits of caregiving), access to workplace supports, and covariates (e.g., caregiver demographics, health, social support, and service utilization). Ninety-five caregivers, recruited through community agency partners, completed the survey. Respondents were predominately female (89%), middle-aged (M = 57), non-Hispanic White (64%) or Latino/a (22%), and caring for a parent (40%) or spouse (30%) for over one year. Half (51%) reported working full- or part-time jobs, while 16.4% had stopped working because of caregiving. In multivariate regression modeling, predictors of financial strain included the care recipients' financial strain and the caregiver's reduction or ceasing of work. Medicare may be protective to minimize caregivers' need to reduce or cease work. Implications for caregivers' ability to stay engaged in the workforce and prepare for their own retirement are explored.


Fungal Diversity Revisited: 2.2 to 3.8 Million Species.
The question of how many species of Fungi there are has occasioned much speculation, with figures mostly posited from around half a million to 10 million, and in one extreme case even a sizable portion of the spectacular number of 1 trillion. Here we examine new evidence from various sources to derive an updated estimate of global fungal diversity. The rates and patterns in the description of new species from the 1750s show no sign of approaching an asymptote and even accelerated in the 2010s after the advent of molecular approaches to species delimitation. Species recognition studies of (semi-)cryptic species hidden in morpho-species complexes suggest a weighted average ratio of about an order of magnitude for the number of species recognized after and before such studies. New evidence also comes from extrapolations of plant:fungus ratios, with information now being generated from environmental sequence studies, including comparisons of molecular and fieldwork data from the same sites. We further draw attention to undescribed species awaiting discovery in biodiversity hot spots in the tropics, little-explored habitats (such as lichen-inhabiting fungi), and material in collections awaiting study. We conclude that the commonly cited estimate of 1.5 million species is conservative and that the actual range is properly estimated at 2.2 to 3.8 million. With 120,000 currently accepted species, it appears that at best just 8%, and in the worst case scenario just 3%, are named so far. Improved estimates hinge particularly on reliable statistical and phylogenetic approaches to analyze the rapidly increasing amount of environmental sequence data.


One Hospital Department with Three Affiliated Medical Schools - Yea or Nay? A Cross-sectional Survey of Students and Tutors.
This article was migrated. The article was marked as recommended. Background The experience of teaching students from multiple medical schools with separate curriculums and learning ethos within a single healthcare institution is not well-documented in literature. Objective We aimed to identify the benefits and challenges of having students from three medical schools train within one department from the clinical tutors' and medical students' viewpoint. Methods This was a cross-sectional study at KK Women's and Children's Hospital (KKH). A survey was conducted on clinical tutors and students from three medical schools for their viewpoints on a 5-point Likert scale. Results 91 of 100 (91%) students and 51 of 60 (85%) tutors returned the survey. 95.6% of students and 94.1% of tutors agreed that it was important for KKH to be involved in the teaching of all three medical schools. 83.5% of students and 76.5% of tutors believed they would benefit from shared teaching and learning materials. 84.3% of tutors and 83.6% of students agreed that they could be exposed to new teaching methods while 84.7% of students and 72.5% of tutors believed that opportunities to collaborate between schools would arise. However, 25 (49%) tutors and 58 (63.7%) students believed that there may be limited supervision. Students (60.4%) and tutors (56.9%) alike felt that there would be a lack of learning space. Conclusion Both students and tutors believed that it was important for medical students for the department in KKH to be involved in the teaching of all three medical schools. Benefits perceived included shared teaching and learning resources, exposure to new teaching methods and opportunity for collaboration across medical schools. Through careful planning of rotations and supportive leadership, hospitals can optimise teaching capabilities allowing students and tutors to benefit from advantages of teaching of students from multiple medical schools.


Thyroid Nodule Size as a Predictor of Malignancy in Follicular and Hurthle Neoplasms.
The management of follicular (FN) and Hurthle cell neoplasms (HCN) is often difficult because of the uncertainty of malignancy risk. We aimed to assess characteristics of benign and malignant follicular and Hurthle neoplasms based on their shape and size. Patients with Follicular adenoma (FA) or carcinoma (FC) and Hurthle Cell adenoma (HCA) or carcinoma (HCC) who had preoperative ultrasonography were included. Demographic data were retrieved. Size and shape of the nodules were measured. Logistic regression analyses and odds ratios were performed. A total of 115 nodules with 57 carcinomas and 58 adenomas were included. Logistic regression analysis shows that the nodule height and the patient age are predictors of malignancy (p-values = 0.001 and 0.042). A cutoff value of nodule height ≥ 4 cm. produces an odds ratio of 4.5 (p-value = 0.006). An age ≥ 55 year-old demonstrates an odds ratio of 2.4-3.6 (p-value = 0.03). Taller-than-wide shape was not statistically significant (p-value = 0.613). FC and HCC are larger than FA and HCA in size, with a cutoff at 4 cm. Increasing age increases the odds of malignancy with a cutoff at 55 year-old. Taller-than-wide shape is not a predictor of malignancy.


Recent advances in hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an allergen to which the subject has been previously sensitized. The diagnosis of HP most often relies on an array of nonspecific clinical symptoms and signs developed in an appropriate setting, with the demonstration of interstitial markings on chest radiographs, serum precipitating antibodies against offending antigens, a lymphocytic alveolitis on BAL, and/or a granulomatous reaction on lung biopsies. The current classification of HP in acute, subacute, and chronic phases is now challenged, and a set of clinical predictors has been proposed. Nonspecific interstitial pneumonitis, usual interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia may be the sole histologic expression of the disease. Presumably, like in idiopathic interstitial pneumonia, acute exacerbations of chronic HP may occur without further exposure to the offending antigen. New offending antigens, such as mycobacteria causing hot tub lung and metalworking fluid HP, have recently been identified and have stimulated further research in HP.


Pneumonia burden in elderly patients: a classification algorithm using administrative data.
Pneumonia has traditionally been classified into two subtypes: community-acquired pneumonia (CAP) and nosocomial pneumonia (NP). Recently, a new entity has been defined, called healthcare-associated pneumonia (HCAP). Few studies have investigated the potential of population-based, electronic, healthcare databases to identify the incidences of these three subtypes of pneumonia. The aim of this study was to estimate the burden of the three subtypes of pneumonia in elderly patients (aged 65+ years) in a large region of central Italy. A retrospective cohort study was performed using linked regional Hospital Information System and Mortality Register. All episodes of pneumonia in elderly patients, who were discharged from the hospital in 2006-2008, were selected for the study. Following a validated ICD-9-coding algorithm, incidents of pneumonia events were classified into three groups (HCAP; probable nosocomial pneumonia, PNP; and CAP). Hospitalisation rates were calculated by age group (65-79, 80+), gender, and year, using the population from the Institute of Statistics (ISTAT) census estimates as denominators. A total of 26,239 pneumonia events occurred in 24,338 patients residing in the Lazio region, aged 65+ years: 2257 HCAP, 6775 PNP, and 17,107 CAP. For all subtypes, the proportion of males was greater than females. Comorbidity status was more severe in HCAP than in the other categories. In-hospital mortality, 30-day mortality, and length of hospital stay were twice higher in HCAP than in CAP episodes. The annual incidence rates were 0.7, 2.1, and 5.4 episodes per 1000 residents for HCAP, PNP, and CAP, respectively. From 2006 to 2008, incidence rates slightly increased for all three subtypes. Health care databases can be used to give a timely and inexpensive picture of the epidemiology of pneumonia. HCAP represents a distinct category of pneumonia, with the longest stay, highest mortality, and the greatest comorbidity.


Advance care planning and health literacy in older dialysis patients: qualitative interview study.
Low health literacy among older adults is associated with limited engagement in end-of-life care planning, higher hospitalisation rates and increased mortality. Frequently, older dialysis patients derive no survival benefit from dialysis and their quality of life often deteriorates further on dialysis. Older dialysis patients' values and wishes are frequently unknown during key healthcare decision making and many endure medically intensive end-of-life scenarios. The objectives of this study were to explore older dialysis patients' understanding of haemodialysis, to explore their engagement in end-of-life care planning and to explore their satisfaction with life on haemodialysis. 15 older dialysis patients participated in qualitative semistructured interviews in two haemodialysis units in Ireland. Thematic saturation was reached. Thematic analysis, applied inductively, was used to distill the data. Themes identified included disempowerment among participants reflected limited health literacy, poor advance care planning compromised participant well-being, haemodialysis compromised participants' core values. Health literacy levels among older dialysis patients are poor, patient empowerment is limited and their participation in shared decision making and advance care planning is suboptimal. Consequently, healthcare decision making, including haemodialysis, may jeopardise patients' core values. Improving health literacy through enhanced patient education and improved communication skills training for clinicians is necessary to promote patient participation in shared decision making. Clinician training to facilitate discussion of patients' values and wishes will help guide clinicians and patients towards healthcare decisions most concordant with patients' core values. This approach will optimise the circumstances for patient-centred care.


The safety of hydroquinone.
Hydroquinone is one of the most effective molecules for the treatment of hyperpigmentary disorders, with over 40 years of efficacy and safety data. Concerns over its safety have been raised because of the fact that it is a derivative of benzene and because of the long-term side-effects observed with cosmetic products containing high concentrations of hydroquinone. However, despite 40-50 years use of hydroquinone for medical conditions, there has not been a single documented case of either a cutaneous or internal malignancy associated with this drug. This article reviews the evidence for the safety of hydroquinone in the treatment of hyperpigmentation conditions.


Functional characteristics of the renal interstitium.
The renal interstitial space analyzed as "inulin space" comprises about 13% in the rat. The Starling forces of this compartment are governed by the balance between tubular and capillary fluid transport and also by the leakage of plasma proteins from the blood side. Protein transport will occur in a large-pore system in the peritubular capillary membrane. During control antidiuresis, the interstitial hydrostatic pressure is 2-4 mmHg. The colloid osmotic pressure shows a larger variability but is generally about 5 mmHg. During conditions of depressed capillary reabsorption but unchanged tubular reabsorption, as in saline expansion, the interstitial hydrostatic pressure rises 3-4 times, whereas the colloid osmotic pressure will show a steep fall resulting from the increased fluid entry and unchanged protein transport. The interstitial volume increases only slightly, since it is compressed by the expanding tubules. The influence of interstitial physical forces on tubular transport remains unclear, mainly due to the inaccessibility of the lateral interspaces to direct measurement of relevant parameters.


Effective connectivity of depth-structure-selective patches in the lateral bank of the macaque intraparietal sulcus.
Extrastriate cortical areas are frequently composed of subpopulations of neurons encoding specific features or stimuli, such as color, disparity, or faces, and patches of neurons encoding similar stimulus properties are typically embedded in interconnected networks, such as the attention or face-processing network. The goal of the current study was to examine the effective connectivity of subsectors of neurons in the same cortical area with highly similar neuronal response properties. We first recorded single- and multi-unit activity to identify two neuronal patches in the anterior part of the macaque intraparietal sulcus (IPS) showing the same depth structure selectivity and then employed electrical microstimulation during functional magnetic resonance imaging in these patches to determine the effective connectivity of these patches. The two IPS subsectors we identified-with the same neuronal response properties and in some cases separated by only 3 mm-were effectively connected to remarkably distinct cortical networks in both dorsal and ventral stream in three macaques. Conversely, the differences in effective connectivity could account for the known visual-to-motor gradient within the anterior IPS. These results clarify the role of the anterior IPS as a pivotal brain region where dorsal and ventral visual stream interact during object analysis. Thus, in addition to the anatomical connectivity of cortical areas and the properties of individual neurons in these areas, the effective connectivity provides novel key insights into the widespread functional networks that support behavior.


Long-term dynamics of fecal corticosterone in male great gerbils (Rhombomys opimus Licht.): effects of environment and social demography.
We examined the relationship among seasonal characteristics of climate, food, and population demography (social structure) and fecal corticosterone (CORT) concentrations over 6 yr in adult males of an arid-adapted species, the great gerbil (Rhombomys opimus Licht., Gerbillidae, Rodentia), as a measure of chronic stress in high, low, and recovering population densities. Results showed yearly differences in the seasonal means of CORT, with the highest concentrations in the year of the highest population density. Analysis of year-specific relationships revealed a positive correlation between mean CORT and total precipitation in January and February and a negative correlation with precipitation in March. In the beginning of spring, when gerbils were in maximum reproductive effort, CORT correlated positively with the saturation of burrow systems and with the number of adult females with an adult male. A linear stepwise regression of CORT in individual males in spring seasons of all 6 yr combined after removal of year effects revealed that CORT depended positively on the number of females associated with a single male but negatively on the abundance of annual herbs. Disappearance of adult males was not related to CORT in most cases. We found no correlation between overall mortality from season to season and mean CORT in either spring (March-May) or fall. In fact, we found a highly negative correlation between mean CORT and the proportion of disappeared males at the beginning of spring. Only at the high population density when cases of probable catastrophic mortality of all adults in the group were excluded was CORT of individual males related positively to their disappearance during the summer drought. Our results suggest that desert rodents with irregular population fluctuations are more sensitive to suppression by external factors than by density-dependent mortality mediated by stress. The favorable feeding and climatic conditions may have compensated for density-dependent increases of CORT and the negative effects it might have had on survival.


A 2D mathematical model for tumor angiogenesis: The roles of certain cells in the extra cellular matrix.
We present a 2D mathematical model of tumor angiogenesis which is an extension of the 1D model originally presented in Levine et al. (2000) [1]. Our model is connected to that 1D model by some transmission and boundary conditions which carry certain cells, the endothelials, pericytes and macrophages from the vessel wall into the extra cellular matrix. In our extended model we also include a mechanism for the action of anti-angiogenic factors such as angiostatin. We present numerical simulations in which we obtain a very good "qualitative agreement" with the time of the onset of vascularization of tumors and with the fact that the capillary tip growth accelerates as it approaches the "tumor".


Laparoscopic nephrectomy for renal diseases in children: is there a learning curve?
We evaluated the impact of a surgeon's experience, divided our first 20 consecutive series that involved a single surgeon at the numerical midpoint of his experience, and compared outcomes regarding this midpoint. From August 1996 to August 2001, laparoscopic nephrectomy or nephroureterectomy was performed in 20 consecutive children, 12 girls and 8 boys aged between 1 and 15 years (median, 5.9 years). Disease was in the right side in 11 patients and in the left side in 9. The children were divided into 2 groups of 10. We retrospectively obtained data on all patients and compared pertinent perioperative information including operation time, blood loss, length of hospital stay, and postoperative complications. The procedure was feasible in all cases and did not require conversion to open surgery or perioperative transfusion in any case. The operation time reduced from a median of 181 minutes over the first 10 patients to 125 minutes over the second 10, and this difference was significant (P = .02). Estimated blood loss and days to the first postoperative oral feeding for the second 10 patients were less than for those of the first 10 but there was no significant difference. The median hospital stay of the first 10 patients was 5.4 days (range, 2-10 days), significantly longer than the 2.5 days of the second 10 (range, 2-7 days) (P = .009). Laparoscopic nephrectomy operation times in children reduced when the surgical experience level exceeded approximately 10 cases.


Ribosome biosynthesis in Tetrahymena pyriformis. Regulation in response to nutritional changes.
Ribosome contents of growing and 12-h-starved Tetrahymena pyriformis (strain B) were compared. These studies indicate that (a) starved cells contain 74% of the ribosomes found in growing cells, (b) growing cells devote 20% of their protein synthetic activity to ribosomal protein production, and (c) less than 3% of the protein synthesized in starved cells is ribosomal protein. Ribosome metabolism was also studied in starved cells which had been refed. For the first 1.5 h after refeeding, there is no change in ribosome number per cell. Between 1.5 and 2 h, there is an abrupt increase in rate of ribosome accumulation but little change in rate of cell division. By 3.5 h, the number of ribosomes per cell has increased to that found in growing cells. At this time, the culture begins to grow exponentially at a normal rate. During the first 2 h after refeeding, cells devote 30-40% of their protein synthetic activity to ribosomal protein production. We estimate that the rate of ribosomal protein synthesis per cell increases at least 80-fold during the first 1-1.5 h after refeeding, reaching the level found in exponentially growing cells. This occurs before any detectable change in ribosome number per cell. The transit time for the incorporation of these newly synthesized proteins into ribosomes is from 1 to 2 h during early refeeding, whereas in exponentially growing cells it is less than 30 min. The relationship between ribosomal protein synthesis and ribosome accumulation is discussed.


Optimization of surgical clip placement for breast-conservation therapy.
The purpose of this study was to determine if seroma cavity visualization could be further improved with placement of gold fiducial markers in each anatomic wall of the seroma cavity compared with placement of surgical titanium clips at the surgeon's discretion. We identified patients with breast cancer who received breast-conservation surgery. Patients were grouped into 3 categories: patients without clips, patients with titanium clips placed at the discretion of the treating surgeon, and patients with gold fiducial markers directly sutured to each wall of the seroma cavity. Cavity visualization was determined using the cavity visualization score criteria. A total of 262 patients met the criteria for the study; 119 patients did not have surgical clips placed during breast-conservation surgery, 109 patients received surgical titanium clip placement at the surgeon's discretion, and 34 patients received directed placement of gold fiducial markers in each anatomic wall of the seroma cavity. There was improvement in the visualization of the seroma cavity in patients who received directed gold fiducial marker placement in each wall of the seroma cavity compared with titanium clip placement at the surgeon's discretion (P < .05). An association was not identified between the quantity of titanium clips used, the amount of seroma walls with titanium clips present, or the time interval between surgery and radiation therapy planning with cavity visualization when surgical titanium clips were placed at the surgeon's discretion. The placement of a gold fiducial marker in each of the seroma cavity walls improved visualization of the seroma cavity compared with the placement of titanium clips at the surgeon's discretion. This technique may be utilized in order to assist in planning a seroma boost following whole breast irradiation or in accelerated partial breast irradiation.


Detection of genomic variations in BRCA1 and BRCA2 genes by long-range PCR and next-generation sequencing.
Advances in sequencing technologies, such as next-generation sequencing (NGS), represent an opportunity to perform genetic testing in a clinical scenario. In this study, we developed and tested a method for the detection of mutations in the large BRCA1 and BRCA2 tumor suppressor genes, using long-range PCR (LR-PCR) and NGS, in samples from individuals with a personal and/or family history of breast and/or ovarian cancer. Eleven LR-PCR fragments, between 3000 and 15,300 bp, containing all coding exons and flanking splice junctions of BRCA1 and BRCA2, were obtained from DNA samples of five individuals carrying mutations in either BRCA1 or BRCA2. Libraries for NGS were prepared using an enzymatic (Nextera technology) method. We analyzed five individual samples in parallel by NGS and obtained complete coverage of all LR-PCR fragments, with an average coding sequence depth for each nucleotide of >30 reads, running from ×7 (in exon 22 of BRCA1) to >×150. We detected and confirmed 100% of the mutations that predispose to the risk of cancer, together with other genomic variations in BRCA1 and BRCA2. Our approach demonstrates that genomic LR-PCR, together with NGS, using the GS Junior 454 System platform, is an effective method for patient sample analysis of BRCA1 and BRCA2 genes. In addition, this method could be performed in regular molecular genetics laboratories.


DFT-Quality Adsorption Simulations in Metal-Organic Frameworks Enabled by Machine Learning Potentials.
Nanoporous materials such as metal-organic frameworks (MOFs) have been extensively studied for their potential for adsorption and separation applications. In this respect, grand canonical Monte Carlo (GCMC) simulations have become a well-established tool for computational screenings of the adsorption properties of large sets of MOFs. However, their reliance on empirical force field potentials has limited the accuracy with which this tool can be applied to MOFs with challenging chemical environments such as open-metal sites. On the other hand, density-functional theory (DFT) is too computationally demanding to be routinely employed in GCMC simulations due to the excessive number of required function evaluations. Therefore, we propose in this paper a protocol for training machine learning potentials (MLPs) on a limited set of DFT intermolecular interaction energies (and forces) of CO2 in ZIF-8 and the open-metal site containing Mg-MOF-74, and use the MLPs to derive adsorption isotherms from first principles. We make use of the equivariant NequIP model which has demonstrated excellent data efficiency, and as such an error on the interaction energies below 0.2 kJ mol-1 per adsorbate in ZIF-8 was attained. Its use in GCMC simulations results in highly accurate adsorption isotherms and heats of adsorption. For Mg-MOF-74, a large dependence of the obtained results on the used dispersion correction was observed, where PBE-MBD performs the best. Lastly, to test the transferability of the MLP trained on ZIF-8, it was applied to ZIF-3, ZIF-4, and ZIF-6, which resulted in large deviations in the predicted adsorption isotherms and heats of adsorption. Only when explicitly training on data for all ZIFs, accurate adsorption properties were obtained. As the proposed methodology is widely applicable to guest adsorption in nanoporous materials, it opens up the possibility for training general-purpose MLPs to perform highly accurate investigations of guest adsorption.


Acetylcholinesterase in human thymus cells.
Acetylcholinesterase (AChE) was long thought to be an enzyme found specifically at the sites of nerve synapses and neuromuscular junctions. It has also been found to occur, however, in cells that are not involved with neurotransmission. This study presents the ultrastructural localization of AChE activity in human thymus cells, using the indirect thiocholine method. Cytochemical demonstration of the enzyme was based on the coupling of acetylthiocholine iodide hydrolysis to the precipitation of heavy metal salts. AChE activity was selectively revealed in the perinuclear cisternae, within the endoplasmic reticulum, and in the Golgi complex of thymic lymphocytes and epithelial cells. Evidence of the presence of reaction product in the latter cells was also found in vesicles that opened into the extracellular space. This is the first demonstration of AChE in human thymus cells. Its possible physiologic role in the thymus gland is discussed.


A prospective study of diagnosis of Toxoplasma gondii infection after bone marrow transplantation.
Active infection with Toxoplasma gondii in immunocompromised transplant recipients can lead to toxoplasmosis, which may have a rapid disease course and in some cases be fatal. It is of paramount importance to diagnose toxoplasmosis at an early stage, and to initiate specific treatment to improve the outcome. Polymerase chain reaction (PCR) is today the primary diagnostic tool to diagnose toxoplasmosis in immunocompromised patients. Timely diagnosis may, however, be difficult if toxoplasmosis is at first asymptomatic. To investigate the magnitude of toxoplasmosis after bone marrow transplantation (BMT), we conducted a screening study by PCR where 21 autologous and 12 allogeneic BMT recipients were included. Peripheral blood samples were taken one week prior to BMT; thereafter, blood samples were drawn weekly for the first 6 months, and monthly up to one year after BMT. The samples were analyzed by conventional PCR and real-time PCR. T. gondii DNA was detected in peripheral blood from one patient 5 days post allogeneic BMT. There were no clinical signs of toxoplasmosis. Medical records were reviewed and showed a previously undiagnosed eye infection in another allogeneic BMT recipient. These two patients were seropositive for T. gondii. We concluded that monitoring for T. gondii DNA in peripheral blood samples using PCR might be a valuable method for identifying toxoplasma-seropositive stem cell transplant recipients.


Major Birth Defects after Vaccination Reported to the Vaccine Adverse Event Reporting System (VAERS), 1990 to 2014.
Major birth defects are important infant outcomes that have not been well studied in the postmarketing surveillance of vaccines given to pregnant women. We assessed the presence of major birth defects following vaccination in the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system used to monitor the safety of vaccines in the United States. We searched VAERS for reports of major birth defects during January 1, 1990, through December 31, 2014. We excluded birth defects from vaccines that had been studied in pregnancy registries or other epidemiological studies (e.g., human papilloma virus, varicella, measles/mumps/rubella, and anthrax vaccines). Birth defects were categorized into trimester of vaccination and classified based on the organs and/or systems affected. If several birth defects affecting different systems were described, we classified those as multiple body systems. Empirical Bayesian data mining was used to assess for disproportionate reporting. We identified 50 reports of major birth defects; in 28 reports, the vaccine was given during the first trimester; 25 were reports with single vaccines administered. Birth defects accounted for 0.03% of all reports received by VAERS during the study period and 3.2% of pregnancy reports; reported defects affected predominately the musculoskeletal (N = 10) or nervous (N = 10) systems. No unusual clusters or specific birth defects were identified. This review of the VAERS database found that major birth defects were infrequently reported, with no particular condition reported disproportionally. Birth defects after routine maternal vaccination will continue to be monitored in VAERS for signals to prompt future studies. Birth Defects Research 109:1057-1062, 2017. © 2017 Wiley Periodicals, Inc.


The Development of the Improving Participation after Stroke Self-Management Program (IPASS): An Exploratory Randomized Clinical Study.
There is a heavy emphasis in rehabilitation on restoration of function post-stroke at the expense of addressing how to manage the impact of stroke and the environment long term. Management of chronic health conditions is often and effectively addressed using self-management education; however, self-management is mostly focused on managing symptoms and health behaviors, not additional participation and community reintegration issues experienced following stroke. This study evaluated the Improving Participation after Stroke Self-Management Program (IPASS) to improve self-efficacy and participation in everyday life activities for individuals living with the long-term consequences of stroke. A multisite, single-blind, exploratory randomized clinical study was conducted with participants with mild-to-moderate chronic stroke (n = 185). Participants were randomized either to receive the IPASS intervention immediately or to a wait list control group. The assessment was completed pre- and post-intervention and at 6-9 months post-intervention follow-up. The primary outcome assessments included measures of self-efficacy to manage chronic health conditions and to participate in everyday life activities. The results show that there was significant short-term increase in health-related self-efficacy both within-group and between-groups in managing chronic conditions which were retained at follow-up; the average effect size was 0.46, indicating moderate effect overall. Further, a significant short-term increase was found in participation self-efficacy, with an overall moderate effect size of 0.55. These results provide early support for the use of IPASS to help improve self-efficacy to manage health behaviors and to improve participation post-stroke. Further investigation is warranted to confirm these findings with an active control group and a more sensitive outcome measure to capture participation changes.


A comparison of the haemodynamic effect of isosorbide-5-mononitrate and isosorbide dinitrate administered in intravenous injection to patients with acute myocardial infarction.
The haemodynamic effects of 10 mg of isosorbide-5-mononitrate (IS-5-MN) and 10 mg of isosorbide dinitrate (ISDN), administered in intravenous injection, were compared in 16 patients with acute myocardial infarction. The study, using the balloon thermodilution catheter, took 4 hours to complete. Both drugs produced a decrease in pulmonary and peripheral arterial pressure, cardiac index, stroke and stroke work indexes; the effect was present immediately after administration to reach a maximum 3-15 minutes later, after which the values gradually returned to baseline levels. While IS-5-MN resulted in an increase in peripheral arterial resistance, heart rate rose briefly following the administration of ISDN. After IS-5-MN, pulmonary diastolic pressure decreased by 15% and peripheral arterial pressure by 5%, and stroke work index by 12%; the magnitude of decrease was double following the administration of ISDN (30%, 15% and 23%, respectively). The decrease in cardiac and stroke indexes was likewise less pronounced after IS-5-MN than after ISDN, the difference, however, was not statistically significant. Duration of the haemodynamic effect of both drugs was about the same--approximately 3 hours.


ABO blood groups are not associated with treatment response and prognosis in patients with local advanced non- small cell lung cancer.
Lung cancer is the leading cause of cancer death, late diagnosis being the main obstacle to improving the outcomes with stage at diagnosis as an important prognostic factor. Relationships between ABO blood groups and risk of benign or malignant diseases have been observed and in this study, we aimed to investigate whether they might affect prognosis and response to chemoradiotherapy in patients with local advanced non-small cell lung cancer (NSCLC). Eighty-one patients with non-metastatic local advanced NSCLC were included in the study. ABO blood groups were A in 45 (55.6%), B in 7 (8.6%), AB in 8 (9.9%), and O in 21 (25.9%) patients. The patients were also divided two groups according to blood group A (45 patients) and non-A (B, AB and O; 36 patients). Response to chemoradiotherapy was complete remission in 10 (12.3%), disease regression in 42 (51.9%), stable disease in 12 (14.8%), and disease progression in 17 (21.0%) patients. There was no significant difference among ABO blood group categories or between patients with A blood group and those with non-A blood group in terms of responses to chemoradiotherapy (p>0.05). There were also no significant differences regarding overall and disease-free survival rates. The ABO blood group system has no significant effect on prognosis and response to chemoradiotherapy in patients with non-metastatic NSCLC.


Musculoskeletal findings of Loeys-Dietz syndrome.
Loeys-Dietz syndrome is a recently recognized multisystemic disorder caused by mutations in the genes encoding the transforming growth factor-beta receptor. It is characterized by aggressive aneurysm formation and vascular tortuosity. We report the musculoskeletal demographic, clinical, and imaging findings of this syndrome to aid in its diagnosis and treatment. We retrospectively analyzed the demographic, clinical, and imaging data of sixty-five patients with Loeys-Dietz syndrome seen at one institution from May 2007 through December 2008. The patients had a mean age of twenty-one years, and thirty-six of the sixty-five patients were less than eighteen years old. Previous diagnoses for these patients included Marfan syndrome (sixteen patients) and Ehlers-Danlos syndrome (two patients). Spinal and foot abnormalities were the most clinically important skeletal findings. Eleven patients had talipes equinovarus, and nineteen patients had cervical anomalies and instability. Thirty patients had scoliosis (mean Cobb angle [and standard deviation], 30 degrees +/- 18 degrees ). Two patients had spondylolisthesis, and twenty-two of thirty-three who had computed tomography scans had dural ectasia. Thirty-five patients had pectus excavatum, and eight had pectus carinatum. Combined thumb and wrist signs were present in approximately one-fourth of the patients. Acetabular protrusion was present in approximately one-third of the patients and was usually mild. Fourteen patients had previous orthopaedic procedures, including scoliosis surgery, cervical stabilization, clubfoot correction, and hip arthroplasty. Features of Loeys-Dietz syndrome that are important clues to aid in making this diagnosis include bifid broad uvulas, hypertelorism, substantial joint laxity, and translucent skin. Patients with Loeys-Dietz syndrome commonly present to the orthopaedic surgeon with cervical malformations, spinal and foot deformities, and findings in the craniofacial and cutaneous systems. Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.


The role of pulmonary rehabilitation in the lung cancer patient.
Lung cancer is the most common deadly malignancy in the United States. It is estimated that 219,440 men and women in the United States will be diagnosed with lung cancer and 159,390 will die of lung cancer in 2009. The overall 5-year survival rate is 15.6%; however, survival rates are much higher (52.6%) for patients who are diagnosed when the cancer is confined to the primary site. Unfortunately, a minority of patients (15%) are diagnosed at this stage. Although the most effective treatment for lung cancer is surgical resection, many patients have significant underlying chronic lung disease as well as other comorbidities, which may increase perioperative risk and possibly exclude them from undergoing surgery. Preoperative assessment is essential for proper risk stratification, but there are important questions that remain to be answered as to (1) whether preoperative or postoperative pulmonary rehabilitation can result in less perioperative morbidity and mortality, (2) whether the institution of preoperative pulmonary rehabilitation can allow more patients to undergo potentially curative surgical resection, and (3) whether pulmonary rehabilitation can play a role in those patients not eligible for surgery.


Gapless spin liquid ground state in the S = 1/2 vanadium oxyfluoride kagome antiferromagnet [NH4]2[C7H14N][V7O6F18].
The vanadium oxyfluoride [NH(4)](2)[C(7)H(14)N][V(7)O(6)F(18)] (DQVOF) is a geometrically frustrated magnetic bilayer material. The structure consists of S = 1/2 kagome planes of V(4+) d(1) ions with S = 1 V(3+) d(2) ions located between the kagome layers. Muon spin relaxation measurements demonstrate the absence of spin freezing down to 40 mK despite an energy scale of 60 K for antiferromagnetic exchange interactions. From magnetization and heat capacity measurements we conclude that the S = 1 spins of the interplane V(3+) ions are weakly coupled to the kagome layers, such that DQVOF can be viewed as an experimental model for S = 1/2 kagome physics, and that it displays a gapless spin liquid ground state.


Prognosis of manpower requirements to ensure specialist diabetological care in the Czech Republic.
The submitted prognosis of need of personnel to ensure specialist diabetological care in the Czech Republic is based on an analysis of the development of the number of diabetic patients and on analysis of activities which must be provided to diabetics in order to maintain the selected standard of health care. The estimate of the future number of diabetics is assessed by the method of demographic projection for one-year age groups, separately for men and women. The analysis of activities in diabetological care was elaborated from the results of an anonymous survey among diabetologists in the South Moravian region. Reflections on different variants of the standard of provided care respect also the analysis of the hitherto recorded trend in the number of health workers in diabetology and their available time. The estimate of needs is objective and can be applied in specialized diabetological services as well as in a different organization of care of diabetics, e.g. by the general practitioner. The contemporary organization of care of diabetics cannot ensure the required standard of care. The prognosis submits several possible ways how to achieve this standard. The prognosis deals in particular with the number of working hours of doctors but does not omit other categories of health workers.


Bifunctional pH-sensitive Zn(ii)-curcumin nanoparticles/siRNA effectively inhibit growth of human bladder cancer cells in vitro and in vivo.
To overcome drug resistance, the combination of two or more therapeutic strategies with different mechanisms has received much attention in recent years. In this study, a common approach has been used to process curcumin and Zn2+ into colloidal dispersions known as "nanoparticles", which are cheap and easy to prepare with high reproducibility. This novel vehicle has good biocompatibility and high cellular uptake for simultaneously delivering the curcumin drug and siRNA into tumor cells. Complexation of Zn2+ with curcumin enhances the aqueous solubility of the hydrophobic drug curcumin and further improves the cellular uptake and bioavailability. The acid-labile coordination Zn(ii)-O bond in Zn(ii)-curcumin drug nanoparticles (Zn(ii)-Cur NPs) can respond to tumor intracellular acidic pH environments to release curcumin, and promoting acid-triggered intracellular drug release. The positively charged Zn(ii)-Cur NPs can efficiently deliver siRNA into human bladder cancer cells, protect siRNA against enzymatic degradation, and facilitate the escape of loaded siRNA from the endosome into the cytoplasm, which successfully downregulates the targeted EIF5A2 oncogene and consequently inhibits cancer cell growth in vitro and in vivo. Proliferation and migration of cancer cells are inhibited by silencing the expression of EIF5A2 and increasing the ratio of pro-apoptotic BAX to anti-apoptotic BCL-2. In vitro and in vivo experiments have demonstrated that bifunctional Zn(ii)-Cur NPs/siEIF5A2 can combine chemotherapy with gene therapy to afford higher therapeutic efficacy than the individual therapeutic protocols.


The TaCslA12 gene expressed in the wheat grain endosperm synthesizes wheat-like mannan when expressed in yeast and Arabidopsis.
Mannan is a class of cell wall polysaccharides widespread in the plant kingdom. Mannan structure and properties vary according to species and organ. The cell walls of cereal grains have been extensively studied due to their role in cereal processing and to their beneficial effect on human health as dietary fiber. Recently, we showed that mannan in wheat (Triticum aestivum) grain endosperm has a linear structure of β-1,4-linked mannose residues. The aim of this work was to study the biosynthesis and function of wheat grain mannan. We showed that mannan is deposited in the endosperm early during grain development, and we identified candidate mannan biosynthetic genes expressed in the endosperm. The functional study in wheat was unsuccessful therefore our best candidate genes were expressed in heterologous systems. The endosperm-specificTaCslA12 gene expressed in Pichia pastoris and in an Arabidopsis thaliana mutant depleted in glucomannan led to the production of wheat-like linear mannan lacking glucose residues and with moderate acetylation. Therefore, this gene encodes a mannan synthase and is likely responsible for the synthesis of wheat endosperm mannan.


Early (M170) activation of face-specific cortex by face-like objects.
The tendency to perceive faces in random patterns exhibiting configural properties of faces is an example of pareidolia. Perception of 'real' faces has been associated with a cortical response signal arising at approximately 170 ms after stimulus onset, but what happens when nonface objects are perceived as faces? Using magnetoencephalography, we found that objects incidentally perceived as faces evoked an early (165 ms) activation in the ventral fusiform cortex, at a time and location similar to that evoked by faces, whereas common objects did not evoke such activation. An earlier peak at 130 ms was also seen for images of real faces only. Our findings suggest that face perception evoked by face-like objects is a relatively early process, and not a late reinterpretation cognitive phenomenon.


Dorsal hump morphology in pink salmon (Oncorhynchus gorbuscha).
Mature male Pacific salmon (Genus Oncorhynchus) develop a dorsal hump, as a secondary male sexual characteristic, during the spawning period. Previous gross anatomical studies have indicated that the dorsal humps of salmon are mainly composed of cartilaginous tissue (Davidson [1935] J Morphol 57:169-183.) However, the histological and biochemical characteristics of such humps are poorly understood. In this study, the detailed microstructures and components of the dorsal humps of pink salmon were analyzed using histochemical techniques and electrophoresis. In mature males, free interneural spines and neural spines were located in a line near to the median septum of the dorsal hump. No cartilaginous tissue was detected within the dorsal hump. Fibrous and mucous connective tissues were mainly found in three regions of the dorsal hump: i) the median septum, ii) the distal region, and iii) the crescent-shaped region. Both the median septum and distal region consisted of connective tissue with a high water content, which contained elastic fibers and hyaluronic acid. It was also demonstrated that the lipid content of the dorsal hump connective tissue was markedly decreased in the mature males compared with the immature and maturing males. Although, the crescent-shaped region of the hump consisted of connective tissue, it did not contain elastic fibers, hyaluronic acid, or lipids. In an ultrastructural examination, it was found that all of the connective tissues in the dorsal hump were composed of collagen fibers. Gel electrophoresis of collagen extracts from these tissues found that the collagen in the dorsal hump is composed of Type I collagen, as is the case in salmon skin. These results indicate that in male pink salmon the dorsal hump is formed as a result of an increase in the amount of connective tissue, rather than cartilage, and the growth of free interneural spines and neural spines.


Disseminated peritoneal leiomyomatosis.
Leiomyomatosis peritonealis disseminata is a very rare condition characterized by the development of multiple smooth muscle-like nodules in the peritoneal cavity. It is associated with increased serum levels of gonadal steroids. The present report describes a 29-year-old patient underwent transabdominal hysterectomy and Bilateral Salpingo oophorectomy six years ago because of leiomyomatosis peritonealis disseminata. After six years she referred to us again because of retroperitoneal fibroma, another rare entity, during hormone replacement therapy inspite of lack of uterus and previous castration.


Effects of Oxymatrine on the apoptosis of human esophageal carcinoma Eca109 cell line and its mechanism.
The effects of Oxymatrine (Oxy) on the proliferation and apoptosis of human esophageal carcinoma Eca109 cell line and the mechanism were investigated. The human esophageal carcinoma Eca109 cells were cultured in vitro. The Oxy-induced apoptosis of Eca 109 cells was assayed by using flow cytometry. The expressions of p-ERK(1/2), Cyclin D1, p21(waf/cip1), Bax and Bcl-2 were detected by Western blot. Flow cytometry revealed that Oxy could induce the apoptosis of Eca109 cells. Western blot showed that Oxy of different concentrations suppressed the expressions of p-ERK(1/2), Cyclin D1 and Bcl-2, but up-regulated the expression of p21(waf/cip1) and Bax, and the ratio of Bax/Bcl-2 was increased. It was suggested the Oxy could induce the apoptosis of Eca109 cells, which might be related to the upregulation of p21(waf/cip1) and the downregulation of p-ERK(1/2), Cyclin D1 and p21(waf/cip1). The possible pathway may be related to Bcl-2/Bax.


Characterization of plasmids in bacterial fish pathogen.
Plasmid profiles of representative fish pathogens, Aeromonas salmonicida, Aeromonas hydrophila, Vibrio anguillarum, Pasteurella piscicida, Yersinia ruckeri, Edwardsiella tarda, and Renibacterium salmoninarum, were determined by agarose gel electrophoresis with four different plasmid detection methods. A combination of two methods was required to detect the plasmids present in these strains and to calculate precisely the molecular weights of the plasmids. Of 38 strains, 28 harbored one or more plasmids, with the majority of strains demonstrating multiplasmid banding. Similarity in plasmid banding between strains was noted and related to geographic source. Five strains of A. salmonicida possessed six plasmid bands having molecular weights of 8.6 X 10(6), 8.4 X 10(6), 8.1 X 10(6), 3.6 X 10(6), 3.5 X 10(6), and 3.4 X 10(6). Four P. piscicida isolates shared three plasmid bands having molecular weights of 37 X 10(6), 15 X 10(6), and 5 X 10(6), and five A. hydrophila strains harbored a common plasmid having a molecular weight of ca. 20 X 10(6) to 30 X 10(6). The highest-molecular-weight plasmids (145 X 10(6) and 130 X 10(6) were detected in V. anguillarum. From curing experiments, it was found that in A. hydrophila strain 79-62, a loss of resistance to tetracycline was associated with loss of plasmid content in all susceptible derivatives, suggesting plasmid-mediated tetracycline resistance. Cell surface characteristics and metabolic properties were also modified in cured derivatives of A. hydrophila strain 79-62.


Providing Quality of Care in Fragile and Vulnerable Settings: Lessons from South Sudan.
In 2020, the World Health Organization (WHO) released a report concerning planning and actions to provide quality of care in fragile, conflict-affected, and vulnerable areas. South Sudan, the world's newest country, has encountered both natural and man-made disasters in recent years that have posed marked challenges to delivery of care. The Southern Sudan Healthcare Organization (SSHCO) operates as a non-governmental organization (NGO) in this setting, delivering and improving healthcare through war, flooding, and infectious outbreaks. The goal of this paper is to highlight the challenges faced in providing care in South Sudan from an NGO perspective and apply the recent WHO guidelines on quality of care to optimize practical implementation. Each of the WHO's eight elements for quality of care in South Sudan were examined in relation to the experience of SSHCO from 2013-2021. Analysis included: 1. summary of the WHO element; 2. examples of successful implementation; 3. barriers to implementation; and 4. recommendations to improve implementation. The team found that communication and coordination were the most important aspects of improving quality of care in South Sudan. These should be prioritized and include intergovernmental partners, the local and national Ministry of Health (MOH), NGOs, and community stakeholders. Communication and coordination should foster community engagement, improved data collecting and reporting, and sharing of publicly accessible information. Better clinical staff training and governance are also required to ensure the most effective use of limited resources. South Sudan faces many barriers to quality of care with communication and coordination identified among the foremost issues. Practical application of the WHO elements of quality of care can assist NGOs in effectively identifying areas for improvement to deliver better quality essential health services.


An Integrated Framework to Conceptualize and Develop the Vancouver Airways Health Literacy Tool (VAHLT).
There is currently no comprehensive tool to assess the functional health literacy (HL) skills of chronic airway disease (CAD) patients. The purpose of this article is to describe the development of a new HL measure, the Vancouver Airways Health Literacy Tool (VAHLT). The tool was developed through the following phases: (1) Tool conceptualization, consisting of: (A) a systematic review (SR), (B) focus group sessions with CAD patients to understand barriers and facilitators to CAD management, (C) a survey with key-informants to obtain strategies to mitigate self-management barriers and validate patient-derived topics, and (D) respiratory physicians' review of the topics; (2) Scenario and item development; and (3) Tool testing and content validation. The SR identified the lack of a valid HL measurement tool for CAD patients. Patients provided an initial shortlist of disease-related self-care topics. Key-informants helped to finalize topics for inclusion. Respiratory physicians and patients contributed to the development of a scenario-based questionnaire, which was refined during three rounds of testing to develop a 44-item instrument comprising nine self-management passages. We highlight the holistic process of integrating information from the literature with knowledge gained from key stakeholders into our tool framework. Our approach to stakeholder engagement may be of interest to researchers developing similar tools, and could facilitate the development and testing of HL-based interventions to ultimately improve patient outcomes and reduce the burden on the healthcare system.


Should all patients receive extended thromboprophylaxis after resection of primary lung cancer?
The optimal duration of thromboprophylaxis in patients undergoing resection of primary lung cancer is not known. We investigated the incidence of pulmonary emboli and venous thromboembolism in patients undergoing early-stage lung cancer resection and the impact of change from short duration to extended thromboprophylaxis. We reviewed the outcomes of consecutive patients who underwent resection of early-stage primary lung cancer following a change in protocol from inpatient-only to extended thromboprophylaxis to 28 days. Propensity-score matching of control (routine inpatient pharmacologic thromboprophylaxis) and treatment group (extended pharmacologic thromboprophylaxis) was performed. Adjustment for covariates based on the Caprini risk assessment model was undertaken. Thromboembolic outcomes were compared between the 2 groups. Seven hundred fifty consecutive patients underwent resection of primary lung cancer at Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018. Six hundred patients were included for analysis and propensity-score matching resulted in 253 matched pairs. Extended prophylaxis was associated with a significant reduction in pulmonary emboli (10 of 253 patients [4%] vs 1 of 253 patients [0.4%], P = .01). One patient (0.4%) developed a bleeding complication within the treatment cohort. Multivariable logistic regression model demonstrated that extended thromboprophylaxis was independently associated with a reduction in postoperative pulmonary emboli. Patients undergoing lung cancer resection surgery are at moderate-to-high risk of postoperative thromboembolic disease. Extended dalteparin for 28 days is safe and is associated with reduced incidence of pulmonary embolus in patients undergoing resection of early-stage primary lung cancer.


Treatment of murine lupus with cDNA encoding IFN-gammaR/Fc.
IFN-gamma, a pleiotropic cytokine, is a key effector molecule in the pathogenesis of several autoimmune diseases, including lupus. Importantly, deletion of IFN-gamma or IFN-gammaR in several lupus-predisposed mouse strains resulted in significant disease reduction, suggesting the potential for therapeutic intervention. We evaluated whether intramuscular injections of plasmids with cDNA encoding IFN-gammaR/Fc can retard lupus development and progression in MRL-Fas(lpr) mice. Therapy significantly reduced serum levels of IFN-gamma, as well as disease manifestations (autoantibodies, lymphoid hyperplasia, glomerulonephritis, mortality), when treatment was initiated at the predisease stage, particularly when IFN-gammaR/Fc expression was enhanced by electroporation at the injection site. Remarkably, disease was arrested and even ameliorated when this treatment was initiated at an advanced stage. This therapy represents a rare example of disease reversal and makes application of this nonviral gene therapy in humans with lupus (and perhaps other autoimmune/inflammatory conditions) highly promising.


Child health services research. Challenges and opportunities.
The characteristics of childhood as a unique developmental stage of life, the continuity of child health with adult health, and a distinctive child health care system justify a separate focus of health services research on children. Child health services research (CHSR) currently lacks the tools necessary to monitor the impact of health system change on children's health and health care and to compare the effectiveness of alternative treatment modalities. There is an urgent need to build the research capacity of this field of inquiry. Ignoring or minimizing attention to CHSR is both shortsighted and ultimately costly for families and the entire nation. We present arguments for why children merit a separate focus in health services research, identify factors that have led to the failure of appropriate development of CHSR, and offer a set of strategies for how to build the research capacity of the field.


Reflux oesophagitis and clozapine.
In a series of thirty-six patients treated with clozapine we report four cases who developed upper gastrointestinal symptoms suggestive of reflux oesophagitis within 6 weeks of starting this drug. Subsequent endoscopic examination revealed moderately severe erosive oesophagitis in three of them. Of these one had received treatment for a peptic ulcer in the past but the other two had no previous history of any upper gastrointestinal disorder. The pharmacology of clozapine in relation to gastro-oesophageal reflux is discussed.


The etiology of different forms of urticaria in childhood.
Urticaria is a common disease in children. In contrast to the ease of its diagnosis, etiologic factors are often difficult to determine. In order to study whether differences exist among various forms of urticaria in childhood and whether the patterns of different types of urticaria differ between adults and children, we extensively studied the possible causes of urticaria in children. Fifty-four children (23 girls and 31 boys; ages 1-19 years) with various forms of urticaria were included in the study. In all cases, questions about food allergies, food additive intolerance, drug intake, signs of infection, causes of physical urticaria, insect bites, and personal and family history of atopy were asked. Clinical characteristics of the disease, such as duration, recurrence, and associated angioedema and symptoms of anaphylaxis were also investigated. Detailed laboratory tests, including serologic, autoimmune, and allergic analyses, were conducted to reveal the probable etiologies of urticaria. Of the study patients, 68.5% and 31.5% were diagnosed as having acute and chronic urticaria, respectively. The patient group with chronic urticaria was older and included more boys than the acute group. In the acute urticaria group, infection was the most frequently documented cause (48.6%), followed by drugs (5.4%), and food allergies (2.7%), whereas in chronic urticaria, physical factors were the leading cause (52.94%). The most frequently documented infection was urinary tract infection, followed by serologically determined infections of Chlamydia pneumoniae and Helicobacter pylori. In this study we found indications that infections were frequently associated with urticaria, which suggests that urticaria management should include a survey of certain infectious agents in addition to a detailed history.


The effects of state terrorism and exile on indigenous Guatemalan refugee children: a mental health assessment and an analysis of children's narratives.
This study examined the mental health and psychosocial development of 58 Guatemalan Mayan Indian children living in 2 refugee camps in the Mexican state of Chiapas. Conventional assessment instruments were adapted for use in this unique context, and semistructured interviews were utilized to gather phenomenological data from children regarding various developmental, sociocultural, and political topics. Data are presented that show minimal evidence of psychological trauma in this sample, and various factors are suggested to account for this finding. In addition, data are presented showing a positive relationship between children's mental health and the health status (physical and mental) of their mothers. In particular, a strong association was found between depressive symptomatology in girls and poor health status in their mothers. Qualitative data from the interviews are presented, focusing on children's understandings of why their families fled Guatemala, the nature and causes of the violence, and their thoughts and feelings regarding the prospect of returning to Guatemala at some future point.


Elastin is heterogeneously cross-linked.
Elastin is an essential vertebrate protein responsible for the elasticity of force-bearing tissues such as those of the lungs, blood vessels, and skin. One of the key features required for the exceptional properties of this durable biopolymer is the extensive covalent cross-linking between domains of its monomer molecule tropoelastin. To date, elastin's exact molecular assembly and mechanical properties are poorly understood. Here, using bovine elastin, we investigated the different types of cross-links in mature elastin to gain insight into its structure. We purified and proteolytically cleaved elastin from a single tissue sample into soluble cross-linked and noncross-linked peptides that we studied by high-resolution MS. This analysis enabled the elucidation of cross-links and other elastin modifications. We found that the lysine residues within the tropoelastin sequence were simultaneously unmodified and involved in various types of cross-links with different other domains. The Lys-Pro domains were almost exclusively linked via lysinonorleucine, whereas Lys-Ala domains were found to be cross-linked via lysinonorleucine, allysine aldol, and desmosine. Unexpectedly, we identified a high number of intramolecular cross-links between lysine residues in close proximity. In summary, we show on the molecular level that elastin formation involves random cross-linking of tropoelastin monomers resulting in an unordered network, an unexpected finding compared with previous assumptions of an overall beaded structure.


[Serum immunoglobulins in children perinatally exposed to human immunodeficiency virus]
OBJECTIVE: Hypergammaglobulinemia is an early manifestation of perinatal HIV infection. Our objective was to analyze the differences in serum immunoglobulin levels between infected and seroreverter children and their association with clinical outcome. METHODS: We carried out a historical prospective study with 107 infected and 90 seroreverter children. We compared the IgA, IgG, and IgM levels between infected and seroreverters in the first 18 months of life; IgA, IgG, and IgM as surrogate markers of infection; and IgA, IgG, and IgM levels in the first 5 years in infected children, according to clinical outcome. The Mann-Whitney test was used for comparison between groups. Surrogate markers were assessed according to sensitivity, specificity, positive and negative predictive values, and J index. RESULTS: Infected children, when compared to seroreverters, showed significantly higher levels of: IgM from the 1st to the 5th trimester; IgA and IgG from the 2nd to the 6th trimester (P </= 0.05). Levels of IgA >/= 90 mg/dl in the 2nd trimester and IgG >/= 1,700 mg/ dl or 1,200 mg/dl in the 2nd and 3rd trimesters were associated with HIV infection with J indexes of 0.97, 0.92, and 0.93, respectively. Infected children in the B and C categories, compared to those in the N and A, showed higher levels of IgM from the 2nd to the 4th year, and IgA from the 3rd to the 5th year (P </= 0.05). CONCLUSIONS: The temporal progression of IgA, IgG, and IgM levels showed an early and intense stimulation to the synthesis of immunoglobulin in infected children. Clinical and epidemiological indicators showed that such levels may be surrogate markers of infection. Higher IgM and IgA levels from the 2nd to the 5th year in more severely infected children suggest a dysfunction in immune regulation secondary to persistent antigenic stimulation.


Modulations of microbehaviour by associative memory strength in Drosophila larvae.
Finding food is a vital skill and a constant task for any animal, and associative learning of food-predicting cues gives an advantage in this daily struggle. The strength of the associations between cues and food depends on a number of parameters, such as the salience of the cue, the strength of the food reward and the number of joint cue-food experiences. We investigate what impact the strength of an associative odour-sugar memory has on the microbehaviour of Drosophila melanogaster larvae. We find that larvae form stronger memories with increasing concentrations of sugar or odour, and that these stronger memories manifest themselves in stronger modulations of two aspects of larval microbehaviour, the rate and the direction of lateral reorientation manoeuvres (so-called head casts). These two modulations of larval behaviour are found to be correlated to each other in every experiment performed, which is in line with a model that assumes that both modulations are controlled by a common motor output. Given that the Drosophila larva is a genetically tractable model organism that is well suited to the study of simple circuits at the single-cell level, these analyses can guide future research into the neuronal circuits underlying the translation of associative memories of different strength into behaviour, and may help to understand how these processes are organised in more complex systems.


Insights Into Coronary Sinus Reducer Non-Responders.
Refractory angina affects an increasing proportion of the population with advanced coronary artery disease and microvascular dysfunction. Limited effective pharmacological and interventional therapies exist for this patient cohort. The coronary sinus (CS) reducer, recently recommended in the 2019 guidelines of the European Society of Cardiology for the management of chronic refractory angina, is a balloon-expandable, stainless-steel device designed for implantation in the CS. It acts by increasing CS pressure, thereby redistributing blood to ischemic myocardium, relieving symptoms, and improving quality of life. However, between 15%-30% of patients do not respond to this treatment. Six mechanisms appear to explain this poor response to CS reducer therapy: (1) inappropriate patient selection; (2) cardiac venous system heterogeneity; (3) CS size; (4) incomplete device endothelialization; (5) coronary artery disease phenotype and progression; and (6) limited myocardial ischemia at baseline. We hereby review these mechanisms in detail and highlight key areas that should be addressed in order to try and reduce the burden of non-responders following CS reducer implantation.


Nice natives and mean migrants: the evolution of dispersal-dependent social behaviour in viscous populations.
There has been much interest in the evolution of social behaviour in viscous populations. While low dispersal increases the relatedness of neighbours, which tends to promote the evolution of indiscriminate helping behaviour, it can also increase competition between neighbours, which tends to inhibit the evolution of helping and may even favour harming behaviour. In the simplest scenario, these two effects exactly cancel, so that dispersal rate has no impact on the evolution of helping or harming. Here, we show that dispersal rate does matter when individuals can adjust their social behaviour conditional on whether they have dispersed or whether they have remained close to their place of origin. We find that nondispersing individuals are weakly favoured to indiscriminately help their neighbours, whereas dispersing individuals are more readily favoured to indiscriminately harm their neighbours.


Physical demands in elite team handball: comparisons between male and female players.
The aim of the present study was to examine potential differences in the physical demands imposed on male vs. female adult elite team handball players during match-play. Male and female elite team handball players were monitored over a six and five season time span, respectively. Each player was evaluated during match-play by use of video recording and subsequent computerized locomotive and technical match analysis. Furthermore, physiological measurements during match-play, physical testing and anthropometric measurements were performed. Female players (FP, N.=82) covered a longer mean total distance per match (4693±333 m, group means±SD) compared to male players (MP, N.=83, 3945±538 m) when playing full time (P<0.01). FP exercised at a greater relative workload (79.4% of VO2-max) than MP (70.9% of VO2-max, P<0.05), but performed less high-intense running per match (2.5% of total distance covered) than MP (7.9%, P<0.01). FP also spent less time standing still (10.8% of total effective playing time) compared to MP (36.9%, P<0.001) and showed fewer activity changes (663.8±99.7) compared to MP (1482.4±312.6, P<0.001). MP received more tackles in total in offence (34.5±21.3) and performed more tackles in total in defence (29.9±12.3) compared to FP (14.6±9.2, 20.7±9.7, P<0.05). Furthermore, MP performed more high-intense technical playing actions per match (36.9±13.1) than FP (28.3±11.0, P<0.05). The mean body height and body mass differed between MP (189.6±5.8 cm, 91.7±7.5 kg) and FP (175.4±6.1 cm, 69.5±6.5 kg, P<0.001). Substantial gender-specific differences in the physical demands in elite team handball were observed, with MP performing more high-intense, strength-related playing actions and high-intensity running than FP. Conversely, FP covered a greater total distance and demonstrated a higher relative workload than MP. The physical training of male and female elite team handball players should be designed to reflect these contrasting needs.


Elbow monoarthritis: an atypical onset of juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition in childhood and an important cause of short and long term disability. Oligoarthritis is defined as an arthritis that affects four o fewer joints during the first 6 months of disease. The large majority of patients within this category belongs to a quite well defined disease which is not observed in adults. It is characterized by an early onset (before 6 years of age), an asymmetric arthritis involving mainly large joints, a female predilection, a high frequency of positive antinuclear antibodies (ANA), a high risk for developing chronic iridocyclitis and consistent HLA associations. We describe 3 clinical cases who presented monoarthritis of the elbow as early sign of oligoarticular JIA. All patients showed inflammatory markers elevation and 2/3 were ANA positive. MRI showed the presence of synovial inflammation without bone involvement. Intraarticular triamcinolone hexacetonide, led to remission in one case, while in the other two there was a re-activation of the disease treated with NSAIDs and/or MTX. The reported cases represent 0.6% of 490 patients with JIA followed by our unit in the last 10 years. Cases of exclusive involvement of the elbow at onset of JIA in literature are rare. Therefore, we report 3 cases of monoarthritis of the elbow as initial sign of oligoarticular JIA, a very atypical onset of this disease.


Geographical epidemiology of residence of patients with motor neuron disease in Lancashire and south Cumbria.
To seek objective evidence for geographical clustering of places of residence of patients with motor neuron disease (MND). A complete residential history from birth to onset of disease was obtained from a cohort of 130 patients with MND from Lancashire and south Cumbria presenting to the Department of Neurology in Preston between 1 January 1989 and 31 December 1993. These data were compared with population based reference data from the 1991 UK Census. Some areal units showed a greater, others a lesser, number of MND patient residences than expected. The results suggest that the background population incidence of MND is relatively low and that the overall incidence figures previously quoted have been skewed upwards by areas in which the incidence of MND is relatively increased. These findings were further tested by Poisson modelling. The Poisson model provided a poor fit for the data at postcode district and sector levels confirming that patients with MND were significantly more likely to have lived in some areas than others after allowing for variation in population of the different areal units and for variation in duration of residence. These findings reinforce the results of previous work, much of which has been qualitative rather than quantitative. The results presented here suggest a low background incidence of MND in the context of generally quoted overall incidence figures. This low background incidence is, however, skewed upwards by some areal units with a relatively high incidence, thus achieving overall incidence rates comparable with generally quoted figures. We conclude that there is prima facie evidence of spatial patterns in the distribution of places of residence of patients with MND. Further examination of occupational and environmental factors in the lives of the patients with MND is required to obtain a better understanding of the importance of these findings.


Effects of seasonal change and experimental warming on the temperature dependence of photosynthesis in the canopy leaves of Quercus serrata.
The effects of warming on the temperature response of leaf photosynthesis have become an area of major concern in recent decades. Although growth temperature (GT) and day length (DL) affect leaf gas exchange characteristics, the way in which these factors influence the temperature dependence of photosynthesis remains uncertain. We established open-top canopy chambers at the canopy top of a deciduous forest, in which average daytime leaf temperature was increased by 1.0 °C. We conducted gas exchange measurements for the canopy leaves of deciduous trees exposed to artificial warming during different seasons. The carbon dioxide assimilation rate at 20 °C (A20) was not affected by warming, whereas that at 25 °C (A25) tended to be higher in leaves exposed to warming. Warming increased the optimal temperature of photosynthesis by increasing the activation energy for the maximum rate of carboxylation. Regression analysis indicated that both GT and DL strongly influenced gas exchange characteristics. Sensitivity analysis revealed that DL affected A without obvious effects on the temperature dependence of A, whereas GT almost maintained constant A20 and strongly influenced the temperature dependence. These results indicate that GT and DL have different influences on photosynthesis; GT and DL affect the 'slope' and intercept' of the temperature dependence of photosynthesis, respectively.


Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression.
Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.