Diagnosing celiac disease: a comparison of human tissue transglutaminase antibodies with antigliadin and antiendomysium antibodies.
To evaluate and compare the sensitivity and specificity of the new serologic marker human antitissue transglutaminase antibodies (IgA anti-tTG) with those of antiendomysium (IgA EMA) and antigliadin antibodies (IgA and IgG AGA) for the diagnosis of celiac disease (CD). The level of IgA antibodies to tTG in serum was determined by an enzyme-linked immunosorbent assay (ELISA) test using recombinant human tTG as the antigen; IgA EMA, by indirect immunofluorescence; and IgA and IgG AGA, by ELISA. Sixty-eight serum samples from 59 patients with CD were studied-30 patients had untreated CD, 22 were on gluten-free diets, and 16 had been reintroduced to gluten-and compared with serum samples from 116 children examined for failure to thrive, short stature, various digestive diseases, or other non-CD conditions. Twenty-eight of 30 patients with CD had anti-tTG (the 2 patients whose results were negative were 1 patient with IgA deficiency and 1 infant); 27 of 30 patients had IgA EMA (1 child was IgA anti-tTG positive and IgA EMA negative); 18 of 30 had IgA AGA; and 28 of 30 had IgG AGA. On gluten-free diets, 4 of 22 patients had anti-tTG but none had IgA EMA or IgA AGA. On normal diets, 15 of 15 children who had relapsed had anti-tTG; 9, IgA EMA; 4, IgA AGA; and 8, IgG AGA (1 child did not relapse). In subjects without CD, 3 of 116 had anti-tTG; 12, IgG AGA; and 1, IgA AGA, but none had IgA EMA. In the 3 children who had anti-tTG, CD could be excluded. The positive predictive value of IgA anti-tTG was 90% and the negative predictive value, 98%. In comparison, results for IgA EMA were 100% and 97%, IgA AGA 94% and 90%, and IgG AGA 70% and 98%, respectively. The presence of human anti-tTG is a reliable indicator for the diagnosis and follow-up of CD.


Energy extraction from the biologic battery in the inner ear.
Endocochlear potential (EP) is a battery-like electrochemical gradient found in and actively maintained by the inner ear. Here we demonstrate that the mammalian EP can be used as a power source for electronic devices. We achieved this by designing an anatomically sized, ultra-low quiescent-power energy harvester chip integrated with a wireless sensor capable of monitoring the EP itself. Although other forms of in vivo energy harvesting have been described in lower organisms, and thermoelectric, piezoelectric and biofuel devices are promising for mammalian applications, there have been few, if any, in vivo demonstrations in the vicinity of the ear, eye and brain. In this work, the chip extracted a minimum of 1.12 nW from the EP of a guinea pig for up to 5 h, enabling a 2.4 GHz radio to transmit measurement of the EP every 40-360 s. With future optimization of electrode design, we envision using the biologic battery in the inner ear to power chemical and molecular sensors, or drug-delivery actuators for diagnosis and therapy of hearing loss and other disorders.


Canine and feline intracranial meningiomas: an updated review.
Meningiomas are the most common primary brain tumours in dogs and cats. There are several morphological phenotypes of this extra-axial neoplasm and they show predilections for certain anatomical locations. There have been a number of attempts to apply the current World Health Organization (WHO) classification for human meningiomas to dogs and cats and to obtain a universal classification scheme for domestic animals. Recently, certain enzymes involved in tumour growth have been recognised as biological markers and have been related to degrees of malignancy. The secondary effects of meningiomas have also been investigated, and vascular endothelial growth factor and peritumoural oedema have been reported to reduce survival rate. Breed and age predisposition are recognised in both dogs and cats and the presenting clinical signs are quite consistent. Magnetic resonance imaging and computed tomography are the techniques of choice for the presumptive diagnosis of meningiomas in domestic animals but advanced imaging techniques are constantly being developed and applied. Treatment methods for meningiomas involve a combination of de-bulking surgery, chemotherapy and radiotherapy, and detailed accounts of several treatment protocols have been reported.


SP-B and SP-C alter diffusion in bilayers of pulmonary surfactant.
The hydrophobic proteins SP-B and SP-C promote rapid adsorption of pulmonary surfactant to an air/water interface by an unknown mechanism. We tested the hypothesis that these proteins accelerate adsorption by disrupting the structure of the lipid bilayer, either by a generalized increase in fluidity or by a focal induction of interfacial boundaries within the bilayer. We used fluorescence recovery after photobleaching to measure diffusion of nitrobenzoxadiazolyl-dimyristoyl-phosphatidylethanolamine between 11 and 54 degrees C in multilayers containing the complete set of lipids and proteins in calf lung surfactant extract (CLSE), or the complete set of neutral and phospholipids without the proteins. Above 35 degrees C, Arrhenius plots of diffusion were parallel for CLSE and neutral and phospholipids, but shifted to lower values for CLSE, suggesting that the proteins rigidify the lipid bilayer rather than producing the proposed increase in membrane fluidity. The slopes of the Arrhenius plots for CLSE were steeper below 35 degrees C, suggesting that the proteins induce phase separation at that temperature. The mobile fraction fell below 27 degrees C, consistent with a percolation threshold of coexisting gel and liquid-crystal phases. The induction of lateral phase separation in CLSE, however, does not correlate with apparent changes in adsorption kinetics at this temperature. Our results suggest that SP-B and SP-C accelerate adsorption through a mechanism other than the disruption of surfactant bilayers, possibly by stabilizing a high-energy, highly curved adsorption intermediate.


Hepatitis B subvirus particles display both a fluid bilayer membrane and a strong resistance to freeze drying: a study by solid-state NMR, light scattering, and cryo-electron microscopy/tomography.
Hepatitis B surface antigen (HBsAg) subvirus particles produced from yeast share immunological determinants with mature viruses, which enable the use of HBsAg as a potent antigen for human vaccination. Because the intimate structure of such pseudoviral particles is still a matter of debate, we investigated the robustness of the external barrier and its structure and dynamics using the noninvasive solid-state NMR technique. This barrier is made of 60% proteins and 40% lipids. Phospholipids represent 83% of all lipids, and chain unsaturation is of 72%. Dynamics was reported by embedding small amounts of deuterium chain-labeled unsaturated phospholipid into the external barrier of entire subviral particles, while controlling particle integrity by cryoelectron microscopy, tomography, and light scattering. Variable preparation modes were used, from mild incubation of small unilamellar vesicles to very stringent incorporation with freeze-drying. A lipid bilayer structure of 4- to 5-nm thickness was evidenced with a higher rigidity than that of synthetic phospholipid vesicles, but nonetheless reflecting a fluid membrane (50-52% of maximum rigidity) in agreement with the elevated unsaturation content. The HBsAg particles of 20- to 24-nm diameter were surprisingly found resistant to lyophilization, in such a way that trapped water inside particles could not be removed. These dual properties bring more insight into the mode of action of native subviral particles and their recombinant counterparts used in vaccines.


Reduction of MRI-targeted biopsies in men with low-risk prostate cancer on active surveillance by stratifying to PI-RADS and PSA-density, with different thresholds for significant disease.
The fear of undergrading prostate cancer (PCa) in men on active surveillance (AS) have led to strict criteria for monitoring, which have resulted in good long-term cancer-specific survival, proving the safety of this approach. Reducing undergrading, MRI-targeted biopsies are increasingly used in men with low-risk disease despite their undefined role yet. The objective of this study is to investigate the rate of upgrading using MRI-targeted biopsies in men with low-risk disease on AS, stratified on the basis of PI-RADS and PSA-density, with the aim to reduce potential unnecessary repeat biopsy procedures. A total of 331 men were prospectively enrolled following the MRI-PRIAS protocol. MR imaging was according to Prostate Imaging Reporting and Data System (PI-RADSv2) guidelines. Suspicious MRI lesions (PI-RADS 3-5) were additionally targeted by MRI-TRUS fusion biopsies. Outcome measure was upgrading to Gleason score (GS) ≥3+4 with MRI-targeted biopsies, stratified for PI-RADS and PSA-density. In total, 25% (82/331) of men on AS showed upgrading from GS 3+3. Only 3% (11/331) was upgraded to GS ≥8. In 60% (198/331) a suspicious MRI lesion was identified, but in only 41% (82/198) of men upgrading was confirmed. PI-RADS 3, 4 and 5 categorized index lesions, showed upgrading in 30%, 34% and 66% of men, respectively. Stratification to PI-RADS 4-5, instead of PI-RADS 3-5, would have missed a small number of high volume Gleason 4 PCa in PI-RADS 3 category. However, further stratification into PI-RADS 3 lesions and PSA-density <0.15 ng/mL2 could result in a safe targeted biopsy reduction of 36% in this category, without missing any upgrades. Stratification with the combination of PI-RADS and PSA-density may reduce unnecessary additional MRI biopsy testing. Overall, the high rate of detected upgrading in men on AS may result in an unintended tightening of continuing in AS. Since patients, included under current AS criteria showed extremely favorable outcome, there might be no need to further restrict continuing on AS with MRI and targeted biopsies.


Close-Packed Silicon Microelectrodes for Scalable Spatially Oversampled Neural Recording.
Neural recording electrodes are important tools for understanding neural codes and brain dynamics. Neural electrodes that are closely packed, such as in tetrodes, enable spatial oversampling of neural activity, which facilitates data analysis. Here we present the design and implementation of close-packed silicon microelectrodes to enable spatially oversampled recording of neural activity in a scalable fashion. Our probes are fabricated in a hybrid lithography process, resulting in a dense array of recording sites connected to submicron dimension wiring. We demonstrate an implementation of a probe comprising 1000 electrode pads, each 9 × 9 μm, at a pitch of 11 μm. We introduce design automation and packaging methods that allow us to readily create a large variety of different designs. We perform neural recordings with such probes in the live mammalian brain that illustrate the spatial oversampling potential of closely packed electrode sites.


A report on the development and implementation of a preceptorship training programme for registered nurses.
Clinical supervision represents an important aspect in the development of nursing students' clinical skills. At the School of Nursing (SoN) the clinical supervisors employed by the University of the Western Cape (UWC) have limited contact sessions with students in the clinical setting. However, with the increase in student numbers a need was identified to strengthen the support given to nursing students in the service setting. A preceptorship training programme for nurses was developed in 2009, aimed at improving the clinical teaching expertise of professional nurses. The planning phase, based on a preceptorship model, represents a collaborative undertaking by the higher education institution and the nursing directorate of the Provincial Government Western Cape. A two-week, eight credit, short course was approved by the university structures and presented by staff members of the school. The teaching and learning strategies included interactive lectures, small group activities and preceptor-student encounters in simulated and real service settings. Some of the course outcomes were: applying the principles of clinical teaching and learning within the context of adult education, understanding the preceptor role and managing To date, fifty-four participants have attended the course. Following an internal review of the pilot programme in 2010, relevant adjustments to the programme were made. It is recommended that all the stakeholders be involved in the development and implementation of a contextually relevant preceptorship training programme. It is further recommended that the school embarks on an extensive programme evaluation.


The relationship between the genetic counseling profession and the disability community: a commentary.
Since the inception of the field of genetic counseling, the profession has had a tenuous relationship with the disability community. Genetic counselors both offer prenatal diagnostic testing that allows individuals the opportunity to avoid the birth of a child with a disability and they advocate for the rights of individuals who have a disability. Some in the disability rights community have argued that they feel their lives and the lives of the disabled individuals in their families judged by the offer of prenatal genetic diagnosis and by the attitudes of genetic service providers they encounter in clinical settings. Select voices from the disability community fear that the result of developing technologies may contribute to a world less tolerant of disabilities. The available empirical data suggest that genetic counselors do little to counteract these perspectives. Although limited, investigations into the attitudes and practices of genetic counselors suggest that they have a more negative perspective on disabilities than individuals whose lives are directly affected by them and these attitudes may affect their description of disabling conditions in a prenatal setting. The National Society of Genetic Counselors, the organization that represents the profession in the US has more publicly aligned itself with abortion service providers over disease advocacy organizations, thus subjecting itself to the perception of bias. We suggest possible solutions to these criticisms and argue that individually and collectively, genetic counseling professionals should develop and identify opportunities to more fully support and advocate for the needs of a broader spectrum of clients.


3.77 μm fiber laser based on cascaded Raman gain in a chalcogenide glass fiber.
Laser emission is demonstrated at a wavelength of 3.766 μm in a cascaded Raman gain device. The laser cavity is made of two nested pairs of fiber Bragg gratings inscribed in a 2.8 m length of low-loss As2S3 fiber. An erbium-doped fluoride glass quasi-CW fiber laser emitting at 3.005 μm is used to pump the cascaded Raman cavity, which converts the pump wavelength successively to the first and second Stokes orders, respectively at 3.340 and 3.766 μm. A laser output peak power in excess of 100 mW is obtained with a lasing efficiency of about 8.3% with respect to the launched pump power. This represents the highest emission wavelength delivered by a fiber laser operating at room temperature.


XDR-TB: an outcome of programmatic management of TB in India.
A significantly strengthened Revised National Tuberculosis Control Programme (RNTCP) is currently operational in India. In this case-based commentary, we describe the plight of a patient who developed extensive drug-resistant tuberculosis (XDR-TB) despite having received treatment under the RNTCP for a long period. Our aim is to analyse the programmatic management of tuberculosis in India by highlighting and discussing various issues related to the treatment received by the patient. Further, the article explores whether there is a need to incorporate an ethical element into the RNTCP as it stands today.


Diving apart together: call propagation in diving long-finned pilot whales.
Group-living animals must communicate to stay in contact. In long-finned pilot whales, there is a trade-off between the benefits of foraging individually at depth and the formation of tight social groups at the surface. Using theoretical modelling and empirical data of tagged pairs within a group, we examined the potential of pilot whale social calls to reach dispersed group members during foraging periods. Both theoretical predictions and empirical data of tag pairs showed a potential for communication between diving and non-diving group members over separation distances up to 385 m (empirical) and 1800 m (theoretical). These distances match or exceed pilot whale dive depths recorded across populations. Call characteristics and environmental characteristics were analysed to investigate determinants of call detectability. Longer calls with a higher sound pressure level (SPL) that were received in a quieter environment were more often detected than their shorter, lower SPL counterparts within a noisier environment. In a noisier environment, calls were louder and had a lower peak frequency, indicating mechanisms for coping with varying conditions. However, the vulnerability of pilot whales to anthropogenic noise is still of concern as the ability to cope with increasing background noise may be limited. Our study shows that combining propagation modelling and actual tag recordings provides new insights into the communicative potential for social calls in orientation and reunion with group members for deep-diving pilot whales.


Abulia following penetrating brain injury during endoscopic sinus surgery with disruption of the anterior cingulate circuit: case report.
It is common knowledge that the frontal lobes mediate complex human behavior and that damage to these regions can cause executive dysfunction, apathy, disinhibition and personality changes. However, it is less well known that subcortical structures such as the caudate and thalamus are part of functionally segregated fronto-subcortical circuits, that can also alter behavior after injury. CASE PRESENTATION We present a 57 year old woman who suffered penetrating brain injury during endoscopic sinus surgery causing right basal ganglia injury which resulted in an abulic syndrome. Abulia does not result solely from cortical injury but can occur after disruption anywhere in the anterior cingulate circuit--in the case of our patient, most prominently at the right caudate.


Assessment of nonarticular tenderness and prevalence of fibromyalgia in children.
Fibromyalgia syndrome (FS) is most common in midlife, but may be seen at any age. Its prevalence and assessment of tenderness in healthy children is not known. We assessed 338 healthy schoolchildren for tenderness thresholds and prevalence of FS. In all children a point count of 18 tender points (TP) was conducted by thumb palpation and tenderness of some of the TP sites as well as control point sites was further assessed using a Chatillon dolorimeter. All children and their parents were questioned about the presence of widespread pain or aching. Children were considered to have FS if they met the American College of Rheumatology (ACR) criteria for diagnosis of FS. Of the 338 children, 21 (6.2%) had FS. Thresholds of tenderness of 9 TP were 5.0 (1.2) (kg) [mean (standard deviation)] for boys vs 3.6 (0.8) (kg) for girls (p < 0.001). Thresholds of tenderness of the control point sites were 7.1 (1.4) (kg) for boys vs 5.5 (1.1) (kg) for girls (p < 0.001). Thresholds of tenderness of TP and control points in the children with FS were 2.5 (0.4) (kg) and 4.2 (0.5) (kg) vs 4.5 (1.2) (kg) and 6.6 (1.4) (kg) respectively in the children without FS (p < 0.001). We suggest that FS is common in the pediatric age group. Boys have lower tenderness than girls; children with FS have lower thresholds for tenderness both at control and TP compared to the subjects without FS.


A three-dimensional model of the yeast genome.
Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations. Disparate DNA elements co-localize into functionally defined aggregates or 'factories' for transcription and DNA replication. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.


Posterior pole retinal abnormalities in mild asymptomatic FEVR.
To describe the posterior retinal abnormalities in asymptomatic mild familial exudative vitreoretinopathy (FEVR) individuals who are normal in conventional clinical examination. Thirty-eight asymptomatic mild FEVR individuals (38 eyes) and 38 controls (38 eyes) were included in this cross-sectional study. The posterior retinas in each individual appeared normal. The diagnosis of FEVR was made based on a positive FEVR family history and the presence of retinal peripheral avascular zone with other vessel abnormalities. Biometric data from fundus photographs and fluorescein fundus angiography of all subjects were studied. The diameter of the optic disc (DD), the disc-to-macula distance (DM), the ratio of DM/DD, and numbers of retinal vessels radiated from the optic disc were measured. Significant anatomic differences were identified in the eyes of patients with asymptomatic FEVR compared with those of the control subjects. In individuals with stage I or II FEVR, DD was smaller (1605.34 ± 250.60 vs. 1733.39 ± 163.79 μm), DM was larger (5434.08 ± 824.82 vs. 4696.29 ± 257.34 μm), and DM/DD was higher (3.49 ± 0.93 vs. 2.73 ± 0.28) than those of the controls. Peripapillary retinal vessels were increased significantly in FEVR compared with the controls (24.53 ± 3.10 vs. 21.39 ± 2.65). Asymptomatic individuals with stage I or II FEVR had several abnormalities in the posterior pole noted with more retinal vessels, a significantly larger disc-to-macula distance as well as a remarkably smaller optic disc with a decreased horizontal diameter. These findings will facilitate the early diagnosis of FEVR and are important for adequate genetic counseling as well as the prevention and treatment of this disease.


Performance evaluation of receive-diversity free-space optical communications over correlated Gamma-Gamma fading channels.
The efficacy of spatial diversity in practical free-space optical communication systems is impaired by the fading correlation among the underlying subchannels. We consider in this paper the generation of correlated Gamma-Gamma random variables in view of evaluating the system outage probability and bit-error-rate under the condition of correlated fading. Considering the case of receive-diversity systems with intensity modulation and direct detection, we propose a set of criteria for setting the correlation coefficients on the small- and large-scale fading components based on scintillation theory. We verify these criteria using wave-optics simulations and further show through Monte Carlo simulations that we can effectively neglect the correlation corresponding to the small-scale turbulence in most practical systems, irrespective of the specific turbulence conditions. This has not been clarified before, to the best of our knowledge. We then present some numerical results to illustrate the effect of fading correlation on the system performance. Our conclusions can be generalized to the cases of multiple-beam and multiple-beam multiple-aperture systems.


Identification of 315 genes essential for early zebrafish development.
We completed a large insertional mutagenesis screen in zebrafish to identify genes essential for embryonic and early larval development. We isolated 525 mutants, representing lesions in approximately 390 different genes, and we cloned the majority of these. Here we describe 315 mutants and the corresponding genes. Our data suggest that there are roughly 1,400 embryonic-essential genes in the fish. Thus, we have mutations in approximately 25% of these genes and have cloned approximately 22% of them. Re-screens of our collection to identify mutants with specific developmental defects suggest that approximately 50 genes are essential for the development of some individual organs or cell types. Seventy-two percent of the embryonic-essential fish genes have homologues in yeast, 93% have homologues in invertebrates (fly or worm), and 99% have homologues in human. Yeast and worm orthologues of genes that are essential for early zebrafish development have a strong tendency to be essential for viability in yeast and for embryonic development in the worm. Thus, the trait of being a genetically essential gene is conserved in evolution. This mutant collection should be a valuable resource for diverse studies of cell and developmental biology.


Metabolic syndrome: therapeutic considerations.
The metabolic syndrome is a constellation of metabolic risk factors for atherosclerotic cardiovascular disease (ASCVD) occurring in one individual. There are five cardiovascular risk factors that accompany the metabolic syndrome: atherogenic dyslipidemia [elevated apolipoprotein B (apo B), elevated triglyceride, small low-density lipoprotein (LDL) particles, and low high-density lipoprotein (HDL)cholesterol], elevated blood pressure, elevated glucose, a prothrombotic state, and a proinflammatory state. The likelihood of an individual developing metabolic syndrome is enhance by underlying risk factors, notably, obesity, insulin resistance, lack of physical activity, advancing age, and hormonal factors (e.g., androgens and corticosteroids). Besides being at higher risk for ASCVD, persons with the metabolic syndrome are at increased risk for type 2 diabetes. Persons with the metabolic syndrome deserve management in the clinical setting to reduce the risk for both ASCVD and type 2 diabetes. The two major therapeutic strategies for treatment of affected persons are modification of the underlying risk factors and separate drug treatment of the particular metabolic risk factors when appropriate. First-line therapy for underlying risk factors is therapeutic lifestyle changes, i.e., weight loss in obese persons, increased physical activity, and anti-atherogenic diet. These changes will improve all of the metabolic risk factors. Whether use of drugs to reduce insulin resistance is effective, safe, and cost-effective before the onset of diabetes awaits the results of more clinical research. Turning to individual risk components, for atherogenic dyslipidemia, drug therapies that promote lowering of apo B and raise HDL cholesterol will be needed for higher risk patients. Treatment of categorical hypertension with drugs has become standard practice. When hyperglycemia reaches the diabetic level, glucose-lowering agents will become necessary when dietary control is no longer effective, and reduction of a prothrombotic state with low-dose aspirin may be indicated in higher-risk patients.


Analysis of the correlation between endorectal MRI response to neoadjuvant chemotherapy and biochemical recurrence in patients with high-risk localized prostate cancer.
Intermediate end points are desirable to expedite the integration of neoadjuvant systemic therapy into the treatment strategy for high-risk localized prostate cancer. Endorectal magnetic resonance imaging at 1.5 Tesla (1.5T erMRI) response has been utilized as an end point in neoadjuvant trials but has not been correlated with clinical outcomes. Data were pooled from two trials exploring neoadjuvant chemotherapy in high-risk localized prostate cancer. Trial 1 explored docetaxel for 6 months and Trial 2 explored docetaxel plus bevacizumab for 4.5 months, both before radical prostatectomy. erMRI was done at baseline and end of chemotherapy. 1.5T erMRI response, based upon T2W sequences, was recorded. Multivariable Cox regression was undertaken to evaluate the association between clinical parameters and biochemical recurrence. There were 53 evaluable patients in the combined analysis: 20 (33%) achieved a PSA response, 16 (27%) achieved an erMRI partial response and 24 (40%) achieved an erMRI minor response. Median follow-up was 4.2 years, and 33 of 53 evaluable (62%) patients developed biochemical recurrence. On multivariable analysis, PSA response did not correlate with biochemical recurrence (hazard ratio=0.58, 95% confidence interval (CI) 0.25-1.33) and paradoxically erMRI response was associated with a significantly shorter time to biochemical recurrence (hazard ratio=2.47, 95% CI 1.00-6.13). Response by 1.5T erMRI does not correlate with a decreased likelihood of biochemical recurrence in patients with high-risk localized prostate cancer treated with neoadjuvant docetaxel and may be associated with inferior outcomes. These data do not support the use of 1.5T erMRI response as a primary end point in neoadjuvant chemotherapy trials.


Interactions between environment, species traits, and human uses describe patterns of plant invasions.
Although invasive alien species (IAS) are a major threat to biodiversity, human health, and economy, our understanding of the factors controlling their distribution and abundance is limited. Here, we determine how environmental factors, land use, life-history traits of the invaders, residence time, origin, and human usage interact to shape the spatial pattern of invasive alien plant species in South Africa. Relationships between the environmental factors and the extrinsic and intrinsic attributes of species were investigated using RLQ analysis, a multivariate method for relating a species-attribute table to an environmental table by way of a species presence/absence table. We then clustered species according to their position on the RLQ axes, and tested these groups for phylogenetic independence. The first three axes of the RLQ explained 99% of the variation and were strongly related to the species attributes. The clustering showed that, after accounting for environmental factors, the spatial pattern of IAS in South Africa was driven by human uses, life forms, and reproductive traits. The seven clusters of species strongly reflected geographical distribution, but also intrinsic species attributes and patterns of human use. Two of the clusters, centered on the genera Acacia and Opuntia, were phylogenetically non-independent. The remaining clusters comprised species of diverse taxonomic affinities, but sharing traits facilitating invasion in particular habitats. This information is useful for assessing the extent to which the potential spread of recent introductions can be predicted by considering the interaction of their biological attributes, region of origin, and human use.


[Intrauterine transfusión in alloimmunization Rh in México 1987-2008].
Diagnosis, care and prevention of hemolytic disease in fetuses and newborns is the most prominent historical example of a successful medical procedure aimed to abate perinatal morbidity and mortality caused by a disease which for centuries was described only unknown origin. To review the perinatal outcome with intrauterine transfusion (IUT) in severe alloimmunization RhD over 21 years in a referral center of Mexico. The overall survival rate of fetuses and the relations with gestational age, and presence or absence of hydrops was analyzed. The authors present data about alloimmunization and a historical synopsis about IUT in México. A retrospective study was conducted from January 1, 1987, to January 31, 2008. It was collected only RhD immunizations. Primary outcome variables included gestational age and presence or absence of hydrops, type and number of IUT in each case, and we studied fetal and neonatal morbidity. A total of 531 IUTs were performed in 150 fetuses. Severe hydrops was found at start of intrauterine treatment in 67 cases (45%). The survival rate was closely related to absence or presence of hydrops (88 and 60%), respectively. There were 123 liveborn fetuses and the procedure-related fetal loss rate was low (1.9%). This study confirmed good outcome with IUT for fetal anemia and the loss rate was low and similar to another publications. The hydrops was the principal factor in the survival rate because late detection and referral of fetuses is critical for fetal and neonatal outcome.


Unaltered cocaine self-administration in the prenatal LPS rat model of schizophrenia.
Although cocaine abuse is up to three times more frequent among schizophrenic patients, it remains unclear why this should be the case and whether sex influences this relationship. Using a maternal immune activation model of schizophrenia, we tested whether animals at higher risk of developing a schizophrenia-like state are more prone to acquire cocaine self-administration behavior, and whether they show enhanced sensitivity to the reinforcing actions of cocaine or if they are resistant to extinction. Pregnant rats were injected with lipopolysaccharide on gestational day 15 and 16, and the offspring (both male and female) were tested in working memory (T-maze), social interaction and sensorimotor gating (prepulse inhibition of the acoustic startle response) paradigms. After performing these tests, the rats were subjected to cocaine self-administration regimes (0.5mg/kg), assessing their dose-response and extinction. Male rats born to dams administered lipopolysaccharide showed impaired working memory but no alterations to their social interactions, and both male and female rats showed prepulse inhibition deficits. Moreover, similar patterns of cocaine self-administration acquisition, responsiveness to dose shifts and extinction curves were observed in both control and experimental rats. These results suggest that the higher prevalence of cocaine abuse among schizophrenic individuals is not due to a biological vulnerability directly associated to the disease and that other factors (social, educational, economic, familial, etc.) should be considered given the multifactorial nature of this illness.


Physical Environment vs. Social Environment: What Factors of Age-Friendliness Predict Subjective Well-Being in Men and Women?
"Age-Friendly Cities and Communities" is an initiative launched by the WHO in 2007 that has spread to more than 1000 cities and communities around the world. This initiative is based on an integrated physical and social environment for older people, and a model of participatory, collaborative governance. An enabling social environment setting is just as important as material conditions in determining well-being in later life. The objective of this study is to analyze the interaction between age-friendliness (physical and social) and subjective well-being in women and men aged 55 and over in the Basque Country. The methodology was based on a survey of a representative sample (n = 2469 individuals). In order to know the predictive power of age-friendliness over subjective well-being, linear regression models separated by gender were constructed. The predictive models of age-friendliness are composed by different variables for men and women. In both cases, the physical environment variables do not remain in the final model. Among the predictors of well-being in men, the coexistence stands out as a safety and support network. In women, the neighborhood has proved to be a very important resource. The conclusions of this study contribute to literature and interventions promoting more effective strategies that enhance older people well-being, considering the gender perspective.


Inequalities in lung cancer mortality by the educational level in 10 European populations.
Previous studies have shown that due to differences in the progression of the smoking epidemic European countries differ in the direction and size of socioeconomic variations in smoking prevalence. We studied differences in the direction and size of inequalities in lung cancer mortality by the educational level of subjects in 10 European populations during the 1990's. We obtained longitudinal mortality data by cause of death, age, sex and educational level for 4 Northern European populations (England/Wales, Norway, Denmark, Finland), 3 continental European populations (Belgium, Switzerland, Austria), and 3 Southern European populations (Barcelona, Madrid, Turin). Age- and sex-specific mortality rates by educational level were calculated, as well as the age- and sex-specific mortality rate ratios. Patterns of educational inequalities in lung cancer mortality suggest that England/Wales, Norway, Denmark, Finland and Belgium are the farthest advanced in terms of the progression of the smoking epidemic: these populations have consistently higher lung cancer mortality rates among the less educated in all age-groups in men, including the oldest men, and in all age-groups in women up to those aged 60-69 years. Madrid appears to be less advanced, with less educated men in the oldest age-group and less educated women in all age-groups still benefiting from lower lung cancer mortality rates. Switzerland, Austria, Turin and Barcelona occupy intermediate positions. The lung cancer mortality data suggest that inequalities in smoking contribute substantially to the educational differences in total mortality among men in all populations, except Madrid. Among women, these contributions are probably substantial in the Northern European countries and in Belgium, but only small in Switzerland, Austria, Turin and Barcelona, and negative in Madrid. In many European countries, policies and interventions that reduce smoking in less educated groups should be one of the main priorities to tackle socioeconomic inequalities in mortality. In some countries, particularly in Southern Europe, it may not be too late to prevent women in less educated groups from taking up the smoking habit, thereby avoiding large inequalities in mortality in the future in these countries.


Observations on control of glycemia with conventional insulin therapy or continuous subcutaneous insulin infusion.
Determination of glycemic differences between groups treated with continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) was central to the major objective of the study. Assessment of glycemia was based on 24-h inhospital profiles of plasma glucose; pre- and postprandial and bedtime (seven time points) diurnal profiles performed monthly on outpatient samples; and glycosylated hemoglobin (HbA1) measured bimonthly at each center. The correlation between plasma glucose determinations in the central laboratory and in local laboratories was 0.988. Significance of differences between treatments was by analysis of variance and least-squares regression. At baseline, mean inhospital plasma glucose and HbA1 concentrations and insulin dosages were identical in the groups randomized to CSII or CIT. A prompt decrement of indices of glycemic control during CSII was observed such that mean decrements sustained over the 8-mo treatment period in home and in hospital plasma glucose profiles and HbA1 relative to values obtained during CIT (P less than 0.0001). The likelihood of CSII-treated patients achieving glycemic indices within the normal range was increased. The standardization of the mean and the M-value calculated from inhospital glucose profiles during CSII and CIT at 4 and 8 mo indicated that there was less plasma glucose fluctuation during CSII. The method of pooling standardized local HbA1 measurements from the six centers appeared to be an adequate substitute for centrally performed HbA1 determinations. Advantages of inhospital plasma glucose measurements in terms of accuracy and ability to obtain nocturnal samples contrasted with the likelihood of increased realism and superior correlation with HbA1 in home-obtained samples.(ABSTRACT TRUNCATED AT 250 WORDS)


The quality of doctoral nursing education in South Africa.
The number of doctoral programmes in nursing has multiplied rapidly throughout the world. This has led to widespread concern about nursing doctoral education, specifically with regard to the quality of curricula and faculty, as well as to the availability of appropriate institutional resources. In South Africa, no study of these issues has been conducted at a national level. To explore and describe the quality of nursing doctoral education in South Africa from the perspectives of deans, faculty, doctoral graduates and students. A cross-sectional survey design was used. All deans (N = 15; n = 12), faculty (N = 50; n = 26), doctoral graduates (N = 43; n = 26) and students (N = 106; n = 63) at South African nursing schools that offer a nursing doctoral programme (N = 16; n = 15) were invited to participate. Data were collected by means of structured email-mediated Quality of Nursing Doctoral Education surveys. Overall, the graduate participants scored their programme quality most positively of all the groups and faculty scored it most negatively. All of the groups rated the quality of their doctoral programmes as good, but certain problems related to the quality of resources, students and faculty were identified. These evaluations, by the people directly involved in the programmes, demonstrated significant differences amongst the groups and thus provide valuable baseline data for building strategies to improve the quality of doctoral nursing education in South Africa.


Tracing the Enterococci from Paleozoic Origins to the Hospital.
We examined the evolutionary history of leading multidrug resistant hospital pathogens, the enterococci, to their origin hundreds of millions of years ago. Our goal was to understand why, among the vast diversity of gut flora, enterococci are so well adapted to the modern hospital environment. Molecular clock estimation, together with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, place the origins of the enterococci around the time of animal terrestrialization, 425-500 mya. Speciation appears to parallel the diversification of hosts, including the rapid emergence of new enterococcal species following the End Permian Extinction. Major drivers of speciation include changing carbohydrate availability in the host gut. Life on land would have selected for the precise traits that now allow pathogenic enterococci to survive desiccation, starvation, and disinfection in the modern hospital, foreordaining their emergence as leading hospital pathogens.


Preclinical Melanoma Imaging with 68Ga-Labeled α-Melanocyte-Stimulating Hormone Derivatives Using PET.
It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016. The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy. Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle4-cyclo[Asp5-His-D-Phe7-Arg-Trp-Lys10]-NH2, or Nle-CycMSHhex) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT). The goal of this study was to design and evaluate novel peptides for melanoma imaging with positron emission tomography (PET). We designed and synthesized three peptides, DOTA-PEG2-Nle-CycMSHhex (CCZ01047), DOTA-4-amino-(1-carboxymethyl) piperidine (Pip)-Nle-CycMSHhex (CCZ01048), and DOTA-Pip-Pip-Nle-CycMSHhex (CCZ01056). All three peptides exhibited high binding affinity to MC1R with sub-nanomolar Ki values, rapid internalization into B16F10 melanoma cells and high in vivo stability with more than 93% remaining intact at 15 min post-injection (p.i.) in blood plasma. All three 68Ga-labeled tracers produced high contrast PET images in C57BL/6J mice bearing B16F10 tumors, and their respective tumor uptakes were 8.0 ± 3.0, 12.3 ± 3.3, and 6.5 ± 1.4 %ID/g at 1 h p.i. Minimal normal organ activity was observed at 1 h p.i., except for kidneys (5.1 ± 1.4, 4.7 ± 0.5, and 6.2 ± 2.0 %ID/g, respectively), and thyroid (4.1 ± 0.6 %ID/g for CCZ01047 and 2.4 ± 0.6 %ID/g for CCZ01048). Due to high accumulation at tumor sites and rapid background clearance of 68Ga-CCZ01048, we further evaluated it at 2 h p.i., and a tumor uptake of 21.9 ± 4.6 %ID/g was observed, with background activity further decreased. Exceptional image contrast was also achieved, i.e. tumor-to-blood, tumor-to-muscle, tumor-to-bone and tumor-to-kidney ratios were 96.4 ± 13.9, 210.9 ± 20.9, 39.6 ± 11.9 and 4.0 ± 0.9, respectively. A blocking study was also performed by co-injection of excess amount of non-radioactive Ga-coupled of CCZ01048, which confirmed that the tumor uptake was MC1R mediated. In conclusion, the introduction of a cationic Pip linker to Nle-CycMSHhex, CCZ01048, not only improved tumor uptake, but also generated high tumor-to-normal tissue contrast with PET imaging in a preclinical melanoma model. Therefore, CCZ01048 is a promising candidate for PET imaging of melanoma, and potentially as a theranostic agent for radionuclide therapy of melanoma when labeled with α or β emitters.


Rapid Next-Generation Sequencing Method for Prediction of Prostate Cancer Risks.
Prostate cancer is the most commonly diagnosed male cancer and the second leading cause of cancer deaths among men in the United States, with approximately 220,000 new diagnoses and approximately 27,000 deaths each year. Men with clinical low-risk disease can receive active surveillance to safely preserve quality of life, provided that the risk of an undetected aggressive cancer can be managed. Thus, prediction of a tumor's metastatic potential, ideally using only a biopsy sample, is critical to choosing appropriate treatment. We previously proposed and verified a metastasis potential score (MPS) based on regions prone to copy number alterations in metastatic prostate cancer; MPS is highly predictive of metastatic potential in primary tumors. We developed a novel, targeted postligation amplification sequencing approach, which we call the next-generation copy number alteration assay, to efficiently interrogate 902 genomic sites that belong to 194 genomic regions used in the MPS calculation. The assay is designed to work with the latest generation of sequencing platforms to produce estimates of copy number alteration events. The assay's technical reproducibility, robustness to low starting genomic material, and accuracy have been verified. The assay performed very well on cell lines, a cohort of prostate cancer surgical research samples, and matched punched biopsy samples, making it a significant step toward incorporating sequencing techniques for prostate cancer evaluation.


[Apathy: a useful but limited concept].
In the nineties, Marin proposed to define apathy as a clinical syndrome due to a lack of motivation. The syndrome is characterized by a diminished goal-directed overt behaviors, a lack of interest or concern for social and personal activities and a lack of responsiveness to positive and negative events. Apathy is clearly distinct from depression and can be observed in many conditions, in healthy people as well as in psychiatric disorders such as depression or schizophrenia. It is very common in patients with brain lesions involving the frontal lobes, the right hemisphere, but also in degenerative diseases such as Alzheimer's disease. Motivation, considered as the source of apathy by Marin, is not a simple construct. It refers to a complex set of multiple affective and cognitive processes. However, it is considered, either in an energetic acception, as a single quantitative variable, a force which impulses action but not direct behavior or, in a more specific acception, as the factor which direct behavior towards specific actions. The description of apathy by Marin and the scales designed to its assessment, are based on the first acception. The term apathy is only descriptive, such as those of dysphasia or anosognosia. They do not allow to study the mechanisms underlying the motivation disorders, essential process for the management of apathetic patients. A tentative qualitative approach to assess motivation disorders is proposed, using a semi-structured interview. However, it should be stressed that motivation can not be directly assessed: motivation is a concept to explain some behavior disorders and an inference from the study of behavior.


A randomized clinical trial of family therapy in juvenile drug court.
The objective of this article is to examine the effectiveness of 2 theoretically different treatments delivered in juvenile drug court--family therapy represented by multidimensional family therapy (MDFT) and group-based treatment represented by adolescent group therapy (AGT)--on offending and substance use. Intent-to-treat sample included 112 youth enrolled in juvenile drug court (primarily male [88%], and Hispanic [59%] or African American [35%]), average age 16.1 years, randomly assigned to either family therapy (n = 55) or group therapy (n = 57). Participants were assessed at baseline and 6, 12, 18 and 24 months following baseline. During the drug court phase, youth in both treatments showed significant reduction in delinquency (average d = .51), externalizing symptoms (average d = 2.32), rearrests (average d = 1.22), and substance use (average d = 4.42). During the 24-month follow-up, family therapy evidenced greater maintenance of treatment gains than group-based treatment for externalizing symptoms (d = 0.39), commission of serious crimes (d = .38), and felony arrests (d = .96). There was no significant difference between the treatments with respect to substance use or misdemeanor arrests. The results suggest that family therapy enhances juvenile drug court outcomes beyond what can be achieved with a nonfamily based treatment, especially with respect to what is arguably the primary objective of juvenile drug courts: reducing criminal behavior and rearrests. More research is needed on the effectiveness of juvenile drug courts generally and on whether treatment type and family involvement influence outcomes. Clinical Trials.gov, Identified NCT01668303.


The associations of obsessive-compulsive symptom dimensions and general severity with suicidal ideation in patients with obsessive-compulsive disorder: The role of specific stress responses to COVID-19.
Suicidal ideation is prevalent in patients with obsessive-compulsive disorder (OCD); but, during COVID-19, it may be increased. The present study aimed to examine the effects of obsessive-compulsive (OC) symptom dimensions and OCD severity on suicidal ideation by considering the role of stress responses in reaction to COVID-19 in a clinical sample of patients with OCD. In a cross-sectional study, 304 patients with OCD completed measures of OC symptom dimensions, OCD severity, general mental health (depression and anxiety), and COVID-19-related stress. Results showed that after controlling for depression, anxiety, comorbidity, and lifetime suicide attempts, the OC symptom dimensions of responsibility for harm and unacceptable obsessional thoughts as well as general severity had indirect effects on suicidal ideation through the specific stress responses to COVID-19, including traumatic stress and compulsive checking. The study shows that OCD patients with specific OC symptom dimensions and severe OCD are more likely to have suicidal ideation during the pandemic. Further, the specific stress responses to COVID-19 may be an underlying mechanism. Clinicians should carefully assess suicidal ideation in patients with OCD who experience responsibility for harm and unacceptable thoughts, particularly during the pandemic.


Role of CNP in human airways: cGMP-mediated stimulation of ciliary beat frequency.
Ciliated airway epithelial cells contribute to mucociliary transport systems via ciliary beating and electrolyte transport mechanisms. Both of these activities are regulated by agonists acting through intracellular calcium- and adenosine 3',5'-cyclic monophosphate (cAMP)-dependent processes (5, 15, 18, 27). This study examines the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the regulation of both ciliary beat frequency (CBF) and electrolyte transport in human airway epithelia (HAE). In a previous report, cGMP production in HAE was observed after stimulation with either C-type natriuretic peptide (CNP) or sodium nitroprusside (SNP) (6). In this study, CNP was found to increase CBF by 30 +/- 6.9%, and this effect was mimicked by the cGMP analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), but not by sodium nitroprusside. CNP-induced increases in CBF do not appear to be mediated by changes in either intracellular calcium or cAMP levels. Using modified Ussing chambers, we also investigated CNP's potential modulation of sodium and chloride transport rates. Neither CNP, nor SNP, nor 8-BrcGMP altered active ion transport rates. We conclude that CNP regulates ciliary beat via cGMP-dependent mechanisms, whereas no effect of CNP or cGMP on ion transport was detected.


Mindfulness training and systemic low-grade inflammation in stressed community adults: Evidence from two randomized controlled trials.
Mindfulness interventions have garnered significant attention as a complementary health treatment for many physical and psychological conditions. While some research has shown that mindfulness training can decrease psychological and physiological stress responses, it remains unclear whether mindfulness training impacts inflammation-a predictor of poor health outcomes. In addition, little research has examined the active components of mindfulness that may drive health-related improvements. Here, we provide data from two 3-arm randomized controlled trials that examined the effect of mindfulness training on inflammation in stressed community adults. Specifically, we examined whether training individuals to have an accepting attitude towards present moment experiences is a key emotion regulation skill that can lead to decreases in inflammation. Both studies randomly assigned participants to one of three conditions: mindfulness training that taught both attention monitoring and acceptance skills (Monitor+Accept); mindfulness training teaching monitoring without the acceptance component (Monitor Only); or a control condition. Study 1 employed a novel 2-week smartphone-based intervention and Study 2 employed a standard 8-week Mindfulness-Based Stress Reduction (MBSR) intervention. We hypothesized that Monitor+Accept training would lead to reductions in the inflammatory biomarker C-Reactive Protein (CRP) compared to Monitor Only training and control groups. Contrary to this hypothesis, we found that Monitor+Accept mindfulness training did not lead to reductions in CRP. Exploratory analyses combining study subsamples, however, suggest that both mindfulness interventions may reduce CRP in populations at risk for systemic inflammation-midlife-to-older adults and individuals with high BMI. Overall, the present studies contribute significantly to the question of whether mindfulness interventions can reduce systemic markers of low-grade inflammation.


Volume of blood suctioned during vacuum-assisted breast biopsy predicts later hematoma formation.
To evaluate whether the volume of blood suctioned during vacuum-assisted breast biopsy (VABB) is associated with hematoma formation and progression, patient's age and histology of the lesion. 177 women underwent VABB according to standardized protocol. The volume of blood suctioned and hematoma formation were noted at the end of the procedure, as did the subsequent development and progression of hematoma. First- and second-order logistic regression was performed, where appropriate. Cases with hematoma presented with greater volume of blood suctioned (63.8 +/- 44.7 cc vs. 17.2 +/- 32.9 cc; p < 0.001, Mann-Whitney-Wilcoxon test for independent samples, MWW); the likelihood of hematoma formation was increasing till a volume equal to 82.6 cc, at which the second-order approach predicts a maximum. The volume of blood suctioned was positively associated with the duration of the procedure (Spearman's rho = 0.417, p < 0.001); accordingly, hematoma formation was also positively associated with the latter (p = 0.004, MWW). The volume of blood suctioned was not associated with patients' age, menopausal status and histopathological diagnosis. The likelihood of hematoma is increasing along with increasing amount of blood suctioned, reaching a plateau approximately at 80 cc of blood lost.


Relating centromeric topography in fixed human chromosomes to α-satellite DNA and CENP-B distribution.
Despite extensive analyses on the centromere and its associated proteins, detailed studies of centromeric DNA structure have provided limited information about its topography in condensed chromatin. We have developed a method with correlative fluorescence light microscopy and atomic force microscopy that investigates the physical and structural organization of α-satellite DNA sequences in the context of its associated protein, CENP-B, on human metaphase chromosome topography. Comparison of centromeric DNA and protein distribution patterns in fixed homologous chromosomes indicates that CENP-B and α-satellite DNA are distributed distinctly from one another and relative to observed centromeric ridge topography. Our approach facilitates correlated studies of multiple chromatin components comprising higher-order structures of human metaphase chromosomes.


Second trimester medical abortion with mifepristone followed by unlimited dosing of buccal misoprostol in Armenia.
The aim of the study was to assess the efficacy and acceptability of a regimen using mifepristone and buccal misoprostol with unlimited dosing for second trimester abortion in Armenia. Women seeking to terminate 13-22 week pregnancies were enrolled in the study. Participants swallowed 200 mg mifepristone in the clinic and were instructed to return to the hospital for induction 24-48 h later. During induction, women were given 400 μg buccal misoprostol every 3 h until the fetus and placenta were expelled. The abortion was considered a success if complete uterine evacuation was achieved without oxytocin or surgery. A total of 120 women with a median gestational age of 18 weeks participated in the study. All women began misoprostol induction around 24 h after taking mifepristone. Complete uterine evacuation was achieved in 119 (99.2%) women. The median induction-to-abortion interval was 10.3 h (range 4-17.4) with a mean of 9.5 ± 2.5 h. A median of four misoprostol doses (range 2-6) with a mean of 4 ± 1 misoprostol doses were administered. The induction-to-abortion interval, number of misoprostol doses, pain score and analgesia use increased as gestational age advanced. Acceptability of the method was high among both patients and providers. The medical abortion regimen of 200 mg mifepristone followed 24 h later by induction with 400 μg buccal misoprostol administered every 3 h, with no limit on the number of doses used for the termination of pregnancies of 13-22 weeks' gestation is an effective and acceptable option for women.


Changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole: assessment using T*2 and T1 measurements.
The aim of this pilot-study was to evaluate changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole (DIP) by means of MRI. Twenty healthy volunteers were examined using a multi-echo gradient-echo sequence. The differential myocardial signal response due to the blood oxygen level dependent (BOLD) effect was studied under variable conditions of myocardial oxygen supply caused by the vasodilator DIP. Unlike contrast agents (CA) methods, which require at least two injections of CA and DIP, the presented methods require only a single infusion of DIP. To assess changes in myocardial perfusion, a saturation recovery TurboFLASH (SRTFL) sequence with centric reordering for T1 measurements was used with global and slice-selective spin-preparation (five volunteers). The signal response was measured at baseline conditions and when myocardial blood flow was increased during pharmacological stress with DIP. Administration of DIP induced a 17 +/- 9% increase in T2*. Enhanced perfusion resulted in a 15 +/- 5% decrease of T1 after slice-selective spin preparation and a calculated increase in absolute perfusion of about 5.1 ml/(g x min), which reflects coronary reserve. The study shows that DIP-induced alterations in the relationship between myocardial oxygen supply and demand are detectable in healthy volunteers using T2* and T1 measurements. A combination of T2* and T1 examinations could become a useful diagnostic tool for the non-invasive assessment of myocardial oxygenation and perfusion in patients with coronary artery disease (CAD).


Surgically induced weight loss by gastric bypass improves non alcoholic fatty liver disease in morbid obese patients.
To evaluate the effects of surgical weight loss (Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients. A group of 26 morbidly obese patients aged 45 ± 2 years and with a body mass index > 40 kg/m(2) who underwent open surgical weight loss operations had paired liver biopsies, the first at surgery and the second after 16 ± 3 mo of weight loss. Biopsies were evaluated and compared in a blinded fashion. The presence of metabolic syndrome, anthropometric and biochemical variables were also assessed at baseline and at the time of the second biopsy. Percentage of excess weight loss was 72.1% ± 6.6%. There was a reduction in prevalence of metabolic syndrome from 57.7% (15 patients) to 7.7% (2 patients) (P < 0.001). Any significance difference was observed in aspartate aminotransferase or alanine aminotransferase between pre and postsurgery. There were improvements in steatosis (P < 0.001), lobular (P < 0.001) and portal (P < 0.05) inflammation and fibrosis (P < 0.001) at the second biopsy. There were 25 (96.1%) patients with non alcoholic steatohepatitis (NASH) in their index biopsy and only four (15.3%) of the repeat biopsies fulfilled the criteria for NASH. The persistence of fibrosis (F > 1) was present in five patients at second biopsy. Steatosis and fibrosis at surgery were predictors of significant fibrosis postsurgery. Restrictive mildly malabsorptive surgery provides significant weight loss, resolution of metabolic syndrome and associated abnormal liver histological features in most obese patients.


Infectious prions in the saliva and blood of deer with chronic wasting disease.
A critical concern in the transmission of prion diseases, including chronic wasting disease (CWD) of cervids, is the potential presence of prions in body fluids. To address this issue directly, we exposed cohorts of CWD-naïve deer to saliva, blood, or urine and feces from CWD-positive deer. We found infectious prions capable of transmitting CWD in saliva (by the oral route) and in blood (by transfusion). The results help to explain the facile transmission of CWD among cervids and prompt caution concerning contact with body fluids in prion infections.


Use of an accident and emergency department observation ward in the management of head injury.
The management of 405 patients presenting with head injury to an accident and emergency department was assessed. Sixty-nine patients were admitted, although this number should have been 127 according to current guidelines on the management of head injury. Only three attenders were admitted inappropriately according to these guidelines. An accident and emergency observation ward was open on weekdays only; at weekends, patients with head injury were admitted to a general surgical ward. When the observation ward was open, 51 of the 76 patients (67 per cent) presenting with admission criteria were admitted. When closed, only 15 of the 51 patients (29 per cent) with these criteria were admitted. Guidelines were applied effectively to reduce the number of unnecessary admissions, but there was a significant number of patients with minor head injury who were discharged inappropriately. This number was much reduced when an observation ward was available.


Prolonged QT dispersion is associated with pediatric syncope.
Bilici M, Fidancı-Dedeoğlu Z, Demir F, Akın A, Türe M, Balık H, Tan İ, Ertuğrul S. Prolonged QT dispersion is associated with pediatric syncope. Turk J Pediatr 2019; 61: 85-91. We aimed to find out whether QT dispersion can be used as a diagnostic marker in terms of syncope type, and recurrence risk. Fifty-two patients (28 male, 53.8%) admitted to the pediatric cardiology clinic with syncope were compared with 50 healthy controls (28 male, 56%; mean age: 13.8±2.3 years, range: 11-17 years) for QT dispersion (QTd) and other electrocardiographic findings. Gender, age, echocardiography, blood pressure while standing and sitting, electrolyte levels, liver and kidney function tests, and QTd and QTcd (calculated with corrected QT: QTc) in electrocardiography (ECG) of patients were all evaluated. Patients` ages varied between 7-17 years and the mean age at first syncope was 13.9±2.4 years. Mean follow-up duration of the patients was 10±5 months (range: 5-18 months). Mean number of syncope attacks was 2.8±2.2. QTd (72±46 ms vs. 34±14 ms) and QTcd (77±45 ms vs. 33±14 ms) values of the patients were significantly longer, compared to control group (p < 0.001). The age, gender, QTd, and QTcd values did not differ between the subtypes of syncope based on pathogenetic mechanism. Additionally, these parameters did not differ in terms of the number of syncope recurrence and tilt test. Patients` complaints reduced after cardiologic evaluation and advice regarding prevention of syncope. We think that in follow-up period, education and preventive precautions that can be taken in the daily life must be emphasized, and drug treatment can be started in unresponsive cases.


Characterization of Plasmodium falciparum isolated from the Amazon region of Brazil: evidence for quinine resistance.
The prevalence and severity of drug-resistant malaria is emerging rapidly in the Amazon basin of Brazil. In support of clinical trials using the new antimalarial drug combination of atovaquone and proguanil, we performed in vitro drug sensitivities, molecular characterization of parasite populations using the circumsporozoite protein, merozoite surface antigen-1 (MSA-1), and MSA-2 markers, and an analysis of the Plasmodium falciparum multidrug resistance (pfmdr1) gene sequence and copy number in 26 isolates of P. falciparum obtained in a gold-mining endemic area in Peixoto de Azevedo, Mato Grosso State. All 26 isolates were found to be resistant to chloroquine (50% inhibitory concentration [IC50] = 100-620 nM) and sensitive to mefloquine (IC50 < 23 nM) and halofantrine (IC50 < 6 nM). The isolates also show reduced susceptibility to quinine (IC50 = 48-280 nM). Sequence analysis of the pfmdr1 gene revealed Asn, Phe, Cys, Asp, and Tyr in positions 86, 184, 1034, 1042, and 1246, respectively. These point mutations were similar to that previously described in other Brazilian isolates. Southern blot analysis revealed no amplification of the pfmdr1 gene. These results suggest that three different mechanisms for drug resistance exist for chloroquine, mefloquine, and quinine.


The Benefits of Continuous Leisure Participation in Relocation Adjustment Among Residents of Long-Term Care Facilities.
The rising population of older adults is transforming Taiwan society. Although many long-term care facilities now operate for older adults, the transition from the home environment to long-term facilities may cause multiple issues, including relocation stress syndrome, for new residents. Autonomy is a critical element of the human experience. Leisure, as an expression of autonomy, has been shown to enhance self-image and promote feelings of competence and mastery. The aim of this study was to assess the relationship between participation in leisure activities and adjustment to residential care using the continuity theory. One hundred sixty-three qualified individuals from 11 long-term care institutions were recruited and completed the questionnaire. The sampling criteria for the study were age (55+ years), appropriate cognitive skills, and residency (less than 5 years). Interviews conducted by trained interviewers were used to collect data. Measured outcomes included leisure participation; physical, psychological, and social adjustments; and background information. Cluster analysis, descriptive analysis, multivariate analysis of variance, and least significant difference test were used in analysis. Type of admission (voluntary/mandated) and type of leisure participation significantly affected the level of relocation adjustment success. Four leisure behavior categories were identified, including reduced participation, expanded participation, active participation, and continuing participation. The participants in the active and continuing participation categories had significantly higher psychological adjustment than their peers in the reduced participation category. Moreover, the continuing participation category had a significantly better level of social adjustment than their expanded participation category peers. Continuous and active participation categories had a beneficial outcome in relocation adjustment. The findings support that, in general, residents of long-term care facilities who participate continuously in leisure activities adjust better psychologically and socially to their new life in these facilities than individuals in the other participation categories. As continuity of participation in leisure activities is important for successful aging, institutions should facilitate the continuing leisure behavior of new residents.


Stereotactic radiosurgery for treatment of spinal metastases recurring in close proximity to previously irradiated spinal cord.
As the spinal cord tolerance often precludes reirradiation with conventional techniques, local recurrence within a previously irradiated field presents a treatment challenge. We retrospectively reviewed 51 lesions in 42 patients treated from 2002 to 2008 whose spinal metastases recurred in a previous radiation field (median previous spinal cord dose of 40 Gy) and were subsequently treated with stereotactic radiosurgery (SRS). SRS was delivered to a median marginal dose of 20 Gy (range, 10-30 Gy) in 1-5 fractions (median, 2), targeting a median tumor volume of 10.3 cm(3) (range, 0.2-128.6 cm(3)). Converting the SRS regimens with the linear quadratic model (α/β = 3), the median spinal cord maximum single-session equivalent dose (SSED) was 12.1 Gy(3) (range, 4.7-19.3 Gy(3)). With a median follow-up of 7 months (range, 2-47 months), the Kaplan-Meier local control and overall survival rates at 6/12 months were 87%/73% and 81%/68%, respectively. A time to retreatment of ≤12 months and the combination of time to retreatment of ≤12 months with an SSED of <15 Gy(10) were significant predictors of local failure on univariate and multivariate analyses. In patients with a retreatment interval of <12 months, 6/12 month local control rates were 88%/58%, with a SSED of >15 Gy(10), compared to 45%/0% with <15 Gy(10), respectively. One patient (2%) experienced Grade 4 neurotoxicity. SRS is safe and effective in the treatment of spinal metastases recurring in previously irradiated fields. Tumor recurrence within 12 months may correlate with biologic aggressiveness and require higher SRS doses (SSED >15 Gy(10)). Further research is needed to define the partial volume retreatment tolerance of the spinal cord and the optimal target dose.


Efficacy and safety of Elaeis guineensis and Ficus deltoidea leaf extracts in adults with pre-diabetes.
Individuals with pre-diabetes (fasting glucose 100-125 mg/dl) are at increased risk of developing diabetes; 50% of U.S. adults aged ≥65 y had pre-diabetes in 2005-08. Extracts of the leaves of E. guineensis (a tropical plant producing edible oil), and F. deltoidea (a traditional tea) contain phenolic compounds that have hypoglycemic effects in vitro and in vivo. Therefore, a study of the efficacy and safety of these leaf extracts was undertaken. Otherwise healthy adults with pre-diabetes (15m/15f; aged 21 to 65 y; BMI ≥25 and < 40 kg/m²) were assigned to one of 3 groups for 8 weeks: E. guineensis leaf extract 500 mg or 1000 mg or F. deltoidea leaf extract 1000 mg. Assessments at baseline and throughout the study included: fasting plasma glucose, insulin, OGTT, and HOMA-IR; body weight and waist circumference; vital signs, comprehensive metabolic and lipid panels. Statistical analyses included paired Student's t-test and ANCOVA or non-parametric tests when indicated. E. guineensis intervention for 8 weeks decreased fasting plasma glucose and insulin levels, glucose and insulin areas under the curve, and insulin resistance, and increased insulin sensitivity. The 500 mg dose of E. guineensis had a more consistent effect on reducing glycemia than the 1000 mg dose and the insulin findings at the two dose levels were somewhat inconsistent. Differences in the distribution of baseline insulin levels in the low and high dose groups may explain some of these observed differences in responses. F. deltoidea leaf extract had no effect on glycemia variables but both total and LDL cholesterol concentrations were significantly decreased in this group. There were no significant differences in change of weight; however waist circumference was significantly lower in the E. guineensis groups after intervention. At baseline and after 8 weeks of intervention, vital signs and safety lab tests were within normal limits and not significantly different between groups or due to intervention. These results suggest that the leaf extracts of E. guineensis and F. deltoidea may have positive effects on glucose and lipid levels and are safe for use in humans. Further study is required to determine the maximum effective dosages and the mechanisms of action.


Phylogenetic relationships among tribes in Xylocopinae (Apidae) and implications on nest structure evolution.
The subfamily Xylocopinae has been recognized as the most basal lineage within the family Apidae, comprising four tribes; Allodapini, Ceratinini, Xylocopini and Manueliini. Relationships among the tribes are not well resolved with morphological data. In particular, Manueliini and Xylocopini have each been placed as the most basal lineage in separate analyses of the subfamily. While relationships within each tribe, excepting Manueliini, have been investigated using molecular data, these data have not been applied to examine the relationships among tribes, which remain controversial. Here we present results of molecular phylogenetic analyses using sequences of CoI, Cytb and EF-1alphaF1 from members of the four tribes of Xylocopinae. We used available data from other studies in combination with data generated for the three species of Manueliini. Competing phylogenetic hypotheses regarding the alternate positions proposed to Manueliini and Xylocopini were evaluated through statistical tests. The basal position of either Manueliini or Xylocopini has contrasting implications on the evolutionary history of nest architecture, which mediates the potential for contact between adult and immature individuals. Our results indicate that Manueliini is the most basal lineage of Xylocopinae, in agreement with an evolutionary transition from nests having completely sealed cells to nests lacking cells. A nest structure with closed cells prevents physical interactions between adult and immature stages, whereas an open structure provides the opportunity for interactions that may play an important role in the emergence of sociality.


Atrial fibrillation and acute myocardial infarction: antithrombotic therapy and outcomes.
Atrial fibrillation guidelines recommend long-term use of warfarin according to a patient's predicted risk of stroke. After acute myocardial infarction, however, combining warfarin and antiplatelet medications poses challenges. By using data from more than 69,255 patients with acute myocardial infarction who were enrolled in the National Cardiovascular Data Registry's Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines at 309 hospitals from July 1, 2008, to September 30, 2009, we describe the characteristics and outcomes of the population with myocardial infarction with atrial fibrillation diagnosed within 2 weeks before index myocardial infarction admission (7.1%, N=4947). Use of discharge antithrombotic therapy is described overall and across levels of predicted stroke and bleeding risks. Compared with patients without atrial fibrillation, those with atrial fibrillation before their index myocardial infarction were older and had more comorbidities and worse in-hospital outcomes. Only 32.5% of patients with atrial fibrillation were taking warfarin before their myocardial infarction admission. In these patients, use of warfarin at discharge increased with higher Congestive heart failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS(2)) risk strata (28.5%, 34.6%, and 43.5% for CHADS(2) scores 0, 1, and ≥2; P<.001) and increased in patients at low, intermediate, and high risk of bleeding (25.4%, 42.3%, and 42.1%; P=.004). Triple therapy at discharge (aspirin plus clopidogrel plus warfarin) was used in a minority of this population (14.6%). Use of warfarin at discharge in patients with atrial fibrillation is greater among those with higher stroke and bleeding risks, but despite higher-risk profiles, less than half received warfarin at discharge. These findings highlight that clarification is needed to guide choice of antithrombotic therapy for patients with both atrial fibrillation and acute myocardial infarction.


Hepatitis C virus coinfection as a risk factor for osteoporosis and fracture.
With increased survival of HIV-infected patients, osteoporotic fractures have developed as a major cause of morbidity in these patients, and chronic hepatitis C virus (HCV) coinfection has emerged as a significant contributor to this increased fracture risk. The present article reviews the epidemiologic and clinical evidence for osteoporosis and increased fracture risk among HIV/HCV coinfected patients, and potential mechanisms for these outcomes with HCV coinfection. Epidemiologic studies suggest that HIV/HCV coinfected patients exhibit a three-fold increased fracture incidence compared with uninfected controls, and 1.2-2.4-fold increased fracture risk compared with HIV monoinfected patients. Recent reports suggest that chronic HCV coinfection is independently associated with reduced bone mineral density in HIV, but that it is not associated with significantly increased bone turnover. The deleterious impact of chronic HCV on BMD and fracture risk occurs even in the absence of advanced liver fibrosis or cirrhosis. New tools to assess bone quality, including the trabecular bone score, high-resolution peripheral quantitative computed tomography, and in-vivo microindentation, may help improve understanding of the mechanisms of HCV-associated skeletal fragility. The impact of approved antiosteoporosis medications and direct-acting antivirals for the treatment of chronic HCV infection on patients' bone health remain to be studied. Chronic HCV infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis. The underlying mechanisms are being unraveled, but major questions persist regarding the optimal evaluation and management of bone health in HIV/HCV coinfected patients.


The degeneration of Y chromosomes.
Y chromosomes are genetically degenerate, having lost most of the active genes that were present in their ancestors. The causes of this degeneration have attracted much attention from evolutionary theorists. Four major theories are reviewed here: Muller's ratchet, background selection, the Hill Robertson effect with weak selection, and the 'hitchhiking' of deleterious alleles by favourable mutations. All of these involve a reduction in effective population size as a result of selective events occurring in a non-recombining genome, and the consequent weakening of the efficacy of selection. We review the consequences of these processes for patterns of molecular evolution and variation at loci on Y chromosomes, and discuss the results of empirical studies of these patterns for some evolving Y-chromosome and neo-Y-chromosome systems. These results suggest that the effective population sizes of evolving Y or neo-Y chromosomes are severely reduced, as expected if some or all of the hypothesized processes leading to degeneration are operative. It is, however, currently unclear which of the various processes is most important; some directions for future work to help to resolve this question are discussed.


Diagnosis and management of superior labrum anterior posterior lesions in overhead athletes.
Shoulder pain is a common complaint in overhead athletes, and superior labrum anterior posterior (SLAP) lesions are a common cause of this pain. The pathological cascade which results in the SLAP lesion consists of a combination of posterior inferior capsular tightness and scapular dyskinesis, resulting in a 'peel back' phenomenon at the biceps anchor and leading to the SLAP tear. Physical exam tests vary in their sensitivity and specificity in detecting SLAP lesions, so MRI is helpful in demonstrating the anatomical alteration. Treatment can be conservative, with posterior inferior capsular stretching and scapular open and closed chain exercises. Many SLAP lesions in overhead athletes require surgical treatment that involves repair of the labrum back to the glenoid. Treatment of concomitant injuries such as rotator cuff tears and Bankart lesions in conjunction with the SLAP repair may be necessary.


Cognitive control in majority search: a computational modeling approach.
Despite the importance of cognitive control in many cognitive tasks involving uncertainty, the computational mechanisms of cognitive control in response to uncertainty remain unclear. In this study, we develop biologically realistic neural network models to investigate the instantiation of cognitive control in a majority function task, where one determines the category to which the majority of items in a group belong. Two models are constructed, both of which include the same set of modules representing task-relevant brain functions and share the same model structure. However, with a critical change of a model parameter setting, the two models implement two different underlying algorithms: one for grouping search (where a subgroup of items are sampled and re-sampled until a congruent sample is found) and the other for self-terminating search (where the items are scanned and counted one-by-one until the majority is decided). The two algorithms hold distinct implications for the involvement of cognitive control. The modeling results show that while both models are able to perform the task, the grouping search model fit the human data better than the self-terminating search model. An examination of the dynamics underlying model performance reveals how cognitive control might be instantiated in the brain for computing the majority function.


The use of Arginine Vasopressin in neonates following the Norwood procedure.
Following the Norwood palliation, neonates may require an escalation of inotropic and vasoactive support. Arginine Vasopressin may be uniquely useful in supporting this population. A retrospective evaluation of neonates at this institution between November, 2007 and October, 2010 who received Arginine Vasopressin following the Norwood procedure. Data were recorded from the patient records at one hour prior to, and then 1, 2, 3, 4, 6, and 24 hours following Arginine Vasopressin initiation. We included 28 neonates. The mean dose of Arginine Vasopressin was 0.0005 plus or minus 0.0003 units per kilogram per minute. There was an early response (less than 6 hours) characterised by an 8% increase in systolic blood pressure (p = 0.0004), a 100% increase in urine output (p = 0.02), and a 29% decrease in total fluid administration (p = 0.04). The late response (at 24 hours) revealed further increases in systolic blood pressure and urine output as well as a 53% decrease in serum lactate (p = 0.007) and increase in arterial pH from 7.36 to 7.45 (p less than 0.0001). These changes were not accompanied by increases in heart rate or inotrope score. The initiation of Arginine Vasopressin in post-operative Norwood patients was temporally associated with an improvement in markers of perfusion including systolic blood pressure, urine output, lactate, and pH. Further studies are required to ascertain the efficacy of Arginine Vasopressin in this population.


Sub-lethal effects of pesticide residues in brood comb on worker honey bee (Apis mellifera) development and longevity.
Numerous surveys reveal high levels of pesticide residue contamination in honey bee comb. We conducted studies to examine possible direct and indirect effects of pesticide exposure from contaminated brood comb on developing worker bees and adult worker lifespan. Worker bees were reared in brood comb containing high levels of known pesticide residues (treatment) or in relatively uncontaminated brood comb (control). Delayed development was observed in bees reared in treatment combs containing high levels of pesticides particularly in the early stages (day 4 and 8) of worker bee development. Adult longevity was reduced by 4 days in bees exposed to pesticide residues in contaminated brood comb during development. Pesticide residue migration from comb containing high pesticide residues caused contamination of control comb after multiple brood cycles and provided insight on how quickly residues move through wax. Higher brood mortality and delayed adult emergence occurred after multiple brood cycles in contaminated control combs. In contrast, survivability increased in bees reared in treatment comb after multiple brood cycles when pesticide residues had been reduced in treatment combs due to residue migration into uncontaminated control combs, supporting comb replacement efforts. Chemical analysis after the experiment confirmed the migration of pesticide residues from treatment combs into previously uncontaminated control comb. This study is the first to demonstrate sub-lethal effects on worker honey bees from pesticide residue exposure from contaminated brood comb. Sub-lethal effects, including delayed larval development and adult emergence or shortened adult longevity, can have indirect effects on the colony such as premature shifts in hive roles and foraging activity. In addition, longer development time for bees may provide a reproductive advantage for parasitic Varroa destructor mites. The impact of delayed development in bees on Varroa mite fecundity should be examined further.


Primary health care in practice: usual source of care and health system performance across 14 countries.
Primary health care (PHC) is central to attainment of the Sustainable Development Goals, yet comparable cross-country data on key aspects of primary care have not been widely available. This study analysed data from the People's Voice Survey, which was conducted in 2022 and 2023 in 14 countries. We documented usual source of care across countries and examined associations of usual source of care with core PHC services, quality ratings, and health system confidence. We found that 75% of respondents had a usual source of care, and that 40% of respondents accessed usual care in the public sector at primary level. 44% rated their usual source of care as very good or excellent. Access to PHC-linked screenings and treatments varied widely within and across countries. Having any usual source of care was associated with higher take-up of preventive services, greater access to treatment including mental health services, and greater health system endorsement. Strengthening links between health system users and primary care providers could improve take-up of preventive care and increase user satisfaction with health system performance.


Chronic cough.
Chronic cough is common and distressing, especially against the background of life-threatening illness. It is a symptom that has received scant attention, often eclipsed by pain, breathlessness, nausea and vomiting. This paper reviews the recent literature in cough research: its mechanism, assessment and management. There is so little research from supportive and palliative care that much of our knowledge is extrapolated from research elsewhere. Objective measurement of cough has been facilitated by advances in measuring devices, while subjective assessment tools including cough-specific quality of life questionnaires are now available. These are practical, simple to use and can be incorporated into daily practice. A few drugs have come in and out of favour but there has been no solid advance in therapeutic options in over a decade. The availability of simple assessment tools places the imperative on clinicians to be more systematic in assessment of cough and its interventions. The mainstay of oral therapy for symptom control remains dextromethorphan, codeine and morphine. The potential for research is huge: from basic scientific understanding to clinical trials of innovative therapies.


Intestinal Microbiota and Weight-Gain in Preterm Neonates.
The involvement of the gut microbiota on weight-gain and its relationship with childhood undernutrition and growth has been reported. Thus, the gut microbiota constitutes a potential therapeutic target for preventing growth impairment. However, our knowledge in this area is limited. In this study we aimed at evaluating the relationship among early microbiota, growth, and development in preterm infants. To this end we assessed the levels of specific microorganisms by qPCR, and those of short chain fatty acids by mean of gas-chromatography, in feces from 63 preterm newborns and determined their weight-gain during the first months. The statistical analyses performed indicate an influence of the intestinal microbiota in weight-gain, with the levels of some microorganisms showing a significant association with the weight-gain of the infant. The levels of specific microbial groups during the first days of life were found to affect weight gain by the age of 1 month. Moreover, clustering of the infants on the basis of the microbiota composition at 1 month of age rendered groups which showed differences in weight z-scores. Our results suggest an association between the gut microbiota composition and weight-gain in preterm infants at early life and point out potential microbial targets for favoring growth and maturation in these infants.


Herpes virus infection is associated with vascular remodeling and pulmonary hypertension in idiopathic pulmonary fibrosis.
Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed. Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. A higher frequency of virus positive cases was found in IPF patients than in controls (p = 0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (p = 0.01), poorer performance in the six minute walking test (6MWT; p = 0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004) and higher TGF-β expression (p = 0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p = 0.03), poorer performance in the 6MWT (p = 0.008) and PGD (p = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients. Herpesviral infections may contribute to the development of PH in IPF patients.


Loss of arylformamidase with reduced thymidine kinase expression leads to impaired glucose tolerance.
Tryptophan metabolites have been linked in observational studies with type 2 diabetes, cognitive disorders, inflammation and immune system regulation. A rate-limiting enzyme in tryptophan conversion is arylformamidase (Afmid), and a double knockout of this gene and thymidine kinase (Tk) has been reported to cause renal failure and abnormal immune system regulation. In order to further investigate possible links between abnormal tryptophan catabolism and diabetes and to examine the effect of single Afmid knockout, we have carried out metabolic phenotyping of an exon 2 Afmid gene knockout. These mice exhibit impaired glucose tolerance, although their insulin sensitivity is unchanged in comparison to wild-type animals. This phenotype results from a defect in glucose stimulated insulin secretion and these mice show reduced islet mass with age. No evidence of a renal phenotype was found, suggesting that this published phenotype resulted from loss of Tk expression in the double knockout. However, despite specifically removing only exon 2 of Afmid in our experiments we also observed some reduction of Tk expression, possibly due to a regulatory element in this region. In summary, our findings support a link between abnormal tryptophan metabolism and diabetes and highlight beta cell function for further mechanistic analysis.


Cataract surgery in Southern Ethiopia: distribution, rates and determinants of service provision.
Cataract is the leading cause of blindness worldwide, with the greatest burden found in low-income countries. Cataract surgery is a curative and cost-effective intervention. Despite major non-governmental organization (NGO) support, the cataract surgery performed in Southern Region, Ethiopia is currently insufficient to address the need. We analyzed the distribution, productivity, cost and determinants of cataract surgery services. Confidential interviews were conducted with all eye surgeons (Ophthalmologists & Non-Physician Cataract Surgeons [NPCS]) in Southern Region using semi-structured questionnaires. Eye care project managers were interviewed using open-ended qualitative questionnaires. All eye units were visited. Information on resources, costs, and the rates and determinants of surgical output were collected. Cataract surgery provision is uneven across Southern Region: 66% of the units are within 200 km of the regional capital. Surgeon to population ratios varied widely from 1:70,000 in the capital to no service provision in areas containing 7 million people. The Cataract Surgical Rate (CSR) in 2010 was 406 operations/million/year with zonal CSRs ranging between 204 and 1349. Average number of surgeries performed was 374 operations/surgeon/year. Ophthalmologists and NPCS performed a mean of 682 and 280 cataract operations/surgeon/year, respectively (p = 0.03). Resources are underutilized, at 56% of capacity. Community awareness programs were associated with increased activity (p = 0.009). Several factors were associated with increased surgeon productivity (p < 0.05): working for >2 years, working in a NGO/private clinic, working in an urban unit, having a unit manger, conducting outreach programs and a satisfactory work environment. The average cost of cataract surgery in 2010 was US$141.6 (Range: US$37.6-312.6). Units received >70% of their consumables from NGOs. Mangers identified poor staff motivation, community awareness and limited government support as major challenges. The uneven distribution of infrastructure and personnel, underutilization by the community and inadequate attention and support from the government are limiting cataract surgery service delivery in Southern Ethiopia. Improved human resource management and implementing community-oriented strategies may help increase surgical output and achieve the "Vision 2020: The Right to Sight" targets for treating avoidable blindness.