[Endocrinology in Portugal - Census 2016. Board of the Portuguese College of Endocrinology and Nutrition of the Portuguese Medical Association].
On September 2016, the Board of the College of Endocrinology and Nutrition of the Portuguese Medical Association carried out a national survey, about all Endocrinology, Diabetes and Metabolism Departments of the public hospitals included in the Portuguese National Health Service and a simplified version of this survey was sent to all endocrinologists working in Portugal and registered with the Portuguese Medical Association. Data related to organizational and human resources were collected, reporting the situation by the end of year 2015. The census registered 107 individuals and 27 Departments. The ratio of endocrinologists-population was 1.4, much lower than in the other European countries (varies between 2 to 4), resulting in alarming shortages of services in some areas of Portugal and in worse quality indicators. These data suggest that actions should be taken to increase the number of endocrinologists and departments in the country. In recent years, the number of residents has significantly increased, which will make it possible to correct this situation.


Alarm interventions for nocturnal enuresis in children.
Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15 to 20% of five year olds, and up to 2% of young adults. To assess the effects of alarm interventions on nocturnal enuresis in children, and to compare alarms with other interventions. We searched the Cochrane Incontinence Group specialised trials register (searched 22 November 2004) and the reference lists of relevant articles. All randomised or quasi-randomised trials of alarm interventions for nocturnal enuresis in children were included, except those focused solely on daytime wetting. Comparison interventions included no treatment, simple and complex behavioural methods, desmopressin, tricyclics, and miscellaneous other methods. Two reviewers independently assessed the quality of the eligible trials, and extracted data. Fifty five trials met the inclusion criteria, involving 3152 children of whom 2345 used an alarm. The quality of many trials was poor, and evidence for many comparisons was inadequate. Most alarms used audio methods. Compared to no treatment, about two thirds of children became dry during alarm use (RR for failure 0.38, 95% CI 0.33 to 0.45). Nearly half who persisted with alarm use remained dry after treatment finished, compared to almost none after no treatment (RR of failure or relapse 45/81 (55%) vs 80/81 (99%), RR 0.56, 95% CI 0.46 to 0.68). There was insufficient evidence to draw conclusions about different types of alarm, or about how alarms compare to other behavioural interventions. Relapse rates were lower when overlearning was added to alarm treatment (RR 1.92, 95% CI 1.27 to 2.92) or if dry bed training was used as well (RR 2.0, 95% CI 1.25 to 3.20). Penalties for wet beds appeared to be counter-productive. Alarms using electric shocks were unacceptable to children or their parents. Although desmopressin may have a more immediate effect, alarms appear more effective by the end of a course of treatment (RR 0.71, 95% CI 0.50 to 0.99) and there was limited evidence of greater long-term success (4/22 (18%) vs 16/24 (67%), RR 0.27, 95% CI 0.11 to 0.69). Evidence about the benefit of supplementing alarm treatment with desmopressin was conflicting. Alarms were better than tricyclics during treatment (RR 0.73, 95% CI 0.61 to 0.88) and afterwards (7/12 (58%) vs 12/12 (100%), RR 0.58, 95% CI 0.36 to 0.94). Alarm interventions are an effective treatment for nocturnal bedwetting in children. Alarms appear more effective than desmopressin or tricyclics by the end of treatment, and subsequently. Overlearning (giving extra fluids at bedtime after successfully becoming dry using an alarm), dry bed training and avoiding penalties may further reduce the relapse rate. Better quality research comparing alarms with other treatments is needed, including follow-up to determine relapse rates.


A risk factor for female fertility and pregnancy: celiac disease.
Celiac disease is a genetically-based intolerance to gluten. In the past, celiac disease has been considered a rare disease of infancy characterized by chronic diarrhea and delayed growth. Besides the overt enteropathy, there are many other forms which appear later in life; target organs are not limited to the gut, but include liver, thyroid, skin and reproductive tract. It is now recognized that celiac disease is a relatively frequent disorder; the overall prevalence is at least 1:300 in Western Europe. Celiac disease may impair the reproductive life of affected women, eliciting delayed puberty, infertility, amenorrhea and precocious menopause. Clinical and epidemiological studies show that female patients with celiac disease are at higher risk of spontaneous abortions, low birth weight of the newborn and reduced duration of lactation. No adequate studies are available on the rate of birth defects in the progeny of affected women; however, celiac disease induces malabsorption and deficiency of factors essential for organogenesis, e.g. iron, folic acid and vitamin K. The overall evidence suggests that celiac disease patients can be a group particularly susceptible to reproductive toxicants; however, the pathogenesis of celiac disease-related reproductive disorders still awaits clarification. At present, like the other pathologies associated with celiac disease, the possible prevention or treatment of reproductive effects can only be achieved through a life-long maintenance of a gluten-free diet.


Particle based vaccine formulations for transcutaneous immunization.
Vaccine formulations on the basis of nano- (NP) or microparticles (MP) can solve issues with stabilization, controlled release, and poor immunogenicity of antigens. Likewise transcutaneous immunization (TCI) promises superior immunogenicity as well as the advantages of needle-free application compared with conventional intramuscular injections. Thus the combination of both strategies seems to be a very valuable approach. However, until now TCI using particle based vaccine formulations has made no impact on medical practice. One of the main difficulties is that NPs and MPs cannot penetrate the skin to an extent that would allow the application of the required dose of antigen. This is due to the formidable stratum corneum (SC) barrier, the limited amount of antigen in the formulation and often an insufficient immunogenicity. A multitude of strategies are currently under investigation to overcome these issues. We highlight selected methods presenting a spectrum of solutions ranging from transfollicular delivery, to devices disrupting the SC barrier and the combination of particle based vaccines with adjuvants discussing their advantages and shortcomings. Some of these are currently at an experimental state while others are already in clinical testing. All methods have been shown to be capable of transcutaneous antigen delivery.


Health Disparities Between Sexual Minority and Different-Sex-Attracted Adolescents: Quantifying the Intervening Role of Social Support and School Belonging.
Purpose: An emerging literature documents that sexual minority youth experience significantly and substantially worse health than their heterosexual peers, but few studies have examined the intervening mechanisms linking adolescents' sexual orientation to their health outcomes. This study hypothesized that social support from parents and friends and school belonging would act as important mediators of this relationship and is among the first to test this proposition empirically. Methods: The analyses used rich data from an Australian national probability sample of 14-15-year olds (Longitudinal Study of Australian Children, n = 3204) and regression models to estimate the associations between sexual attraction and four high-quality indicators of adolescent health/well-being capturing health-related quality of life, socio-emotional functioning, depressive symptoms, and life satisfaction. Mediation tests were subsequently performed to quantify the extent to which three scales capturing social support from parents and friends and school belonging mediated the relationships identified. Results: Sexual minority status, social support from parents and friends, and school belonging were significantly related to all health/well-being outcomes. Sexual minority adolescents reported significantly lower levels of support and belonging. Collectively, the support and belonging variables were responsible for 49%-70% of the associations between sexual minority status and the health/well-being outcomes, with school belonging being the most important mediator. Conclusion: These findings have important implications for health equity policy and practice. They suggest that interventions designed to improve the health/well-being of sexual minority adolescents should be directed at eliciting enhanced social support from families and peers and fostering integration at school. School-based interventions may be particularly fruitful.


Directing GDNF-mediated neuronal signaling with proactively programmable cell-surface saccharide-free glycosaminoglycan mimetics.
A significant barrier to harnessing the power of cell-surface glycosaminoglycans (GAGs) to modulate glial cell-line-derived neurotrophic factor (GDNF) signaling is the difficulty in accessing key GAG structures involved. Here, we report tailored GDNF signaling using synthetic polyproline-based GAG mimetics (PGMs). PGMs deliver the much needed proactive programmability for GDNF recognition and effectively modulate GDNF-mediated neuronal processes in a cellular context.


Genotypes and phenotypes of beta lactamase producing strains of Neisseria gonorrhoeae from African countries.
The phenotypes and genotypes of 26 beta lactamase (penicillinase) producing strains of Neisseria gonorrhoeae (PPNG) from African countries were investigated. Using the restriction enzyme technique nine different restriction enzyme patterns were found, two of them in 15 strains. Of the 26 strains, 16 belonged to serogroup WI (containing protein type IA) and 10 to serogroup WII/III (containing protein IB). Among the IA strains four different serovars were represented, whereas six serovars were found among the IB strains. Five different auxotypes were identified, of which proline requiring (found in 12 strains) and prototrophic (found in 10 strains) dominated. Twelve strains harboured a 4.4 megadalton as well as a 24.5 megadalton plasmid. A 3.2 megadalton plasmid was found in 14 strains, one of which also harboured a 24.5 megadalton plasmid. The 2.8 megadalton cryptic plasmid was present in all 26 strains. The MICs of doxycycline ranged from 0.25 to 2.0 mg/l; the MIC 50% for WI strains was 0.25 mg/l and for WII/WIII strains 1.0 mg/l. A total of 10 different combinations of restriction enzyme pattern, serovar, auxotype, and plasmid were seen in the 16 WI strains compared with eight such combinations in the 10 WII/WIII strains. As expected, the restriction enzyme technique and serological classification gave better differentiation than plasmid profiles and susceptibility to doxycycline. More relevantly, however, these techniques also compared favourably with auxotyping. When the different systems were combined, the sensitivity was greatly increased.


Fatty acids and immune function: relevance to inflammatory bowel diseases.
Fatty acids may influence immune function through a variety of mechanisms; many of these are associated with changes in fatty acid composition of immune cell membranes. Eicosanoids produced from arachidonic acid have roles in inflammation and immunity. Increased membrane content of n-3 fatty acids results in a changed pattern of production of eicosanoids, resolvins, and cytokines. Changing the fatty acid composition of immune cells also affects T cell reactivity and antigen presentation. Little attention has been paid to the influence of fatty acids on the gut-associated lymphoid tissue. However, there has been considerable interest in fatty acids and gut inflammation.


Angiosarcoma of the breast with silicone granuloma: a case report.
Angiosarcoma of the breast is a rare non-epithelial tumor and that accounts for less than 0.1% of primary malignancies of the breast. The disease has a relatively higher occurrence among young people, and its prognosis (3-year-survival of only 38%) is extremely poor compared to breast cancer. Here we present a case of an 87-year-old woman who had undergone bilateral breast augmentation with silicone injections in her youth. Although she became aware of a tumor in her right breast, she waited 8 years before seeking treatment. She felt the tumor growing and experienced swelling and pain, but she ended up declining therapy at that time. Two years later she was brought to our hospital by ambulance for continuous bleeding from the same tumor of the breast, which by that time was over 11 cm in diameter. We performed emergency mastectomy. The histological diagnosis was angiosarcoma of the breast with silicone granuloma.


Conservation of ParaHox genes' function in patterning of the digestive tract of the marine gastropod Gibbula varia.
Presence of all three ParaHox genes has been described in deuterostomes and lophotrochozoans, but to date one of these three genes, Xlox has not been reported from any ecdysozoan taxa and both Xlox and Gsx are absent in nematodes. There is evidence that the ParaHox genes were ancestrally a single chromosomal cluster. Colinear expression of the ParaHox genes in anterior, middle, and posterior tissues of several species studied so far suggest that these genes may be responsible for axial patterning of the digestive tract. So far, there are no data on expression of these genes in molluscs. We isolated the complete coding sequences of the three Gibbula varia ParaHox genes, and then tested their expression in larval and postlarval development. In Gibbula varia, the ParaHox genes participate in patterning of the digestive tract and are expressed in some cells of the neuroectoderm. The expression of these genes coincides with the gradual formation of the gut in the larva. Gva-Gsx patterns potential neural precursors of cerebral ganglia as well as of the apical sensory organ. During larval development this gene is involved in the formation of the mouth and during postlarval development it is expressed in the precursor cells involved in secretion of the radula, the odontoblasts. Gva-Xolx and Gva-Cdx are involved in gut patterning in the middle and posterior parts of digestive tract, respectively. Both genes are expressed in some ventral neuroectodermal cells; however the expression of Gva-Cdx fades in later larval stages while the expression of Gva-Xolx in these cells persists. In Gibbula varia the ParaHox genes are expressed during anterior-posterior patterning of the digestive system. This colinearity is not easy to spot during early larval stages because the differentiated endothelial cells within the yolk permanently migrate to their destinations in the gut. After torsion, Gsx patterns the mouth and foregut, Xlox the midgut gland or digestive gland, and Cdx the hindgut. ParaHox genes of Gibbula are also expressed during specification of cerebral and ventral neuroectodermal cells. Our results provide additional support for the ancestral complexity of Gsx expression and its ancestral role in mouth patterning in protostomes, which was secondarily lost or simplified in some species.


Retinal haemorrhage and fatal stroke in an infant with fibromuscular dysplasia.
Non-accidental injury should be suspected and excluded in any infant found to have intracranial and retinal haemorrhage of unknown aetiology. This can be a sensitive issue for both medical staff and parents. We present a case in which the underlying cause of intracranial and retinal haemorrhage was fibromuscular dysplasia. It was a diagnosis made only at postmortem examination and it illustrates the diagnostic difficulty such cases may present.


Angiopoietin-Like Protein 4 and Postprandial Skeletal Muscle Lipid Metabolism in Overweight and Obese Prediabetics.
Angiopoietin-like protein 4 (ANGPTL4) decreases plasma triacylglycerol (TAG) clearance by inhibiting lipoprotein lipase (LPL) and may contribute to impairments in lipid metabolism under compromised metabolic conditions. To investigate the effects of a high-saturated fatty acid (SFA) mixed meal on plasma ANGPTL4 concentrations in relation to in vivo muscle LPL activity, to study the effects of dietary fat quality, and to examine skeletal muscle ANGPTL4 release. Design, Participants, Setting, and Interventions: We used a dual stable-isotope tracer technique in combination with measurements of arteriovenous concentration differences across forearm muscle to investigate muscle ANGPTL4 secretion and fatty acid handling under fasting conditions and after a high-SFA mixed meal in 73 overweight and obese humans at the Metabolic Research Unit of Maastricht University. The effect of dietary fat quality manipulation on plasma ANGPTL4 was investigated in 10 obese insulin-resistant participants. The high-SFA meal decreased circulating ANGPTL4 concentrations (fasting, 5.2 ng/mL; vs 4 hours postprandial, 4.0 ng/mL; P < .001). Furthermore, skeletal muscle ANGPTL4 secretion into the circulation was observed (AUC0-4 h, P = .048). However, no association was observed between plasma ANGPTL4 and skeletal muscle very low-density lipoprotein or dietary (chylomicron) TAG extraction (AUC0-4 h, P = .372 and P = .139, respectively). In contrast to a high-SFA or high-monounsaturated fat meal, plasma ANGPTL4 remained unchanged after a high-polyunsaturated fat meal. ANGPTL4 is secreted by human forearm muscle in postprandial conditions after a high-SFA meal. Plasma ANGPTL4 concentrations were not associated with in vivo skeletal muscle LPL activity after a high-SFA meal. Dietary fat quality affects plasma ANGPTL4, but it remains to be elucidated whether this influences short-term skeletal muscle lipid handling.


New implanted chronic catheter device for determining blood pressure and cardiac output in conscious dog.
The Vascular-Access-Port (VAP) is a subcutaneous implantable device designed for repeated venous blood sampling in humans. With slight modifications the device has been used in the arterial and venous systems of dogs. This device allows for chronic repeated arterial blood pressure monitoring, monitoring of cardiac outputs, and blood sampling in conscious dogs. Infection, vascular thrombosis, and catheter extraction have not occurred. This modified VAP has been used for 6 mo and in 25 dogs to date without any failure to determine arterial blood pressure and cardiac output.


Comparability of histological outcomes in rats and humans in a hernia model.
Hernia repair is one of the most frequently performed operations. In search of the ideal mesh for hernia repair, animal research is required. Although rats are most often used in experimental mesh experiments, no correlation with clinical findings in humans has ever been shown. Therefore, the aim of our study was to investigate whether adhesion formation and foreign body reactions to meshes in rats are comparable with the reactions in humans. A fixed type of mesh was implanted intraperitoneally in a group of 10 rats and 10 patients undergoing elective, temporary stoma formation. In case of the latter, meshes were placed around the stoma. After a follow-up period of 12 wk in rats and after a median follow-up of 6 mo in humans, samples of the mesh were collected. Adhesion assessments were performed, and (immuno-) histochemical evaluation was performed by a specialized experimental pathologist and an experienced clinical pathologist. After the follow-up period, adhesion formation did not differ significantly between rats and humans. Moreover, general inflammation scores were comparable, although granulocytes and giant cells were more present in rats, compared with humans. On the other hand, the presence of fibrosis was more evident in humans compared with rats. To our knowledge, this is the first study, which showed that a specific animal model, namely a rat model, correlates with adhesion formation and the foreign body reaction to meshes in humans. It can be recommended to use rats in future experimental mesh for incisional hernia research.


Modulation of Heme-Induced Inflammation Using MicroRNA-Loaded Liposomes: Implications for Hemolytic Disorders Such as Malaria and Sickle Cell Disease.
Hemolytic disorders, like malaria and sickle cell disease (SCD), are responsible for significant mortality and morbidity rates globally, specifically in the Americas and Africa. In both malaria and SCD, red blood cell hemolysis leads to the release of a cytotoxic heme that triggers the expression of unique inflammatory profiles, which mediate the tissue damage and pathogenesis of both diseases. MicroRNAs (miRNAs), such as miR-451a and let-7i-5p, contribute to a reduction in the pro-inflammatory responses induced by circulating free hemes. MiR-451a targets both IL-6R (pro-inflammatory) and 14-3-3ζ (anti-inflammatory), and when this miRNA is present, IL-6R is reduced and 14-3-3ζ is increased. Let-7i-5p targets and reduces TLR4, which results in anti-inflammatory signaling. These gene targets regulate inflammation via NFκB regulation and increase anti-inflammatory signaling. Additionally, they indirectly regulate the expression of key heme scavengers, such as heme-oxygenase 1 (HO-1) (coded by the HMOX1 gene) and hemopexin, to decrease circulating cytotoxic heme concentration. MiRNAs can be transported within extracellular vesicles (EVs), such as exosomes, offering insights into the mechanisms of mitigating heme-induced inflammation. We tested the hypothesis that miR-451a- or let-7i-5p-loaded artificial EVs (liposomes) will reduce heme-induced inflammation in brain vascular endothelial cells (HBEC-5i, ATCC: CRL-3245) and macrophages (THP-1, ATCC: TIB-202) in vitro. We completed arginase and nitric oxide assays to determine anti- and pro-inflammatory macrophage presence, respectively. We also assessed the gene expression of IL-6R, TLR4, 14-3-3ζ, and NFκB by RT-qPCR for both cell lines. Our findings revealed that the exposure of HBEC-5i and THP-1 to liposomes loaded with miR-451a or let-7i-5p led to a reduced mRNA expression of IL-6R, TLR4, 14-3-3ζ, and NFκB when treated with a heme. It also resulted in the increased expression of HMOX1 and hemopexin. Finally, macrophages exhibited a tendency toward adopting an anti-inflammatory differentiation phenotype. These findings suggest that miRNA-loaded liposomes can modulate heme-induced inflammation and can be used to target specific cellular pathways, mediating inflammation common to hematological conditions, like malaria and SCD.


Auscultating heart and breath sounds through patients' gowns: who does this and does it matter?
Doctors are taught to auscultate with the stethoscope applied to the skin, but in practice may be seen applying the stethoscope to the gown. To determine how often doctors auscultate heart and breath sounds through patients' gowns, and to assess the impact of this approach on the quality of the sounds heard. A sample of doctors in the west of Scotland were sent an email in 2014 inviting them to answer an anonymous questionnaire about how they auscultated heart and breath sounds. Normal heart sounds from two subjects were recorded through skin, through skin and gown, and through skin, gown and dressing gown. These were played to doctors, unaware of the origin of each recording, who completed a questionnaire about the method and quality of the sounds they heard. 206 of 445 (46%) doctors completed the questionnaire. 124 (60%) stated that they listened to patients' heart sounds, and 156 (76%) to patients' breath sounds, through patients' gowns. Trainees were more likely to do this compared with consultants (OR 3.39, 95% CI 1.74 to 6.65). Doctors of all grades considered this practice affected the quality of the sounds heard. 32 doctors listened to the recorded heart sounds. 23 of the 64 (36%) skin and 23 of the 64 (36%) gown recordings were identified. The majority of doctors (74%) could not differentiate between skin or gown recordings, but could tell them apart from the double layer recordings (p=0.02). Trainees were more likely to hear artefactual added sounds (p=0.04). Many doctors listen to patients' heart and breath sounds through hospital gowns, at least occasionally. In a short test, most doctors could not distinguish between sounds heard through a gown or skin. Further work is needed to determine the impact of this approach to auscultation on the identification of murmurs and added sounds.


Dupilumab in chronic rhinosinusitis with nasal polyps: Real life data in a multicentric Sicilian experience.
This study aimed to evaluate the effectiveness and safety of dupilumab during the first year of treatment in a real-life setting, focusing on improvement in nasal polyp score (NPS) as well as specific symptoms, quality of life and olfactory function. A multicentric observational cohort study was carried out. A total of 170 patients were enrolled in the Otorhinolaryngology Unit of the three University Hospitals and considered for dupilumab therapy. All recorder characteristics were age (at the first dupilumab application visit), sex, smoke habits, previous local and systemic corticosteroid therapy, history of endoscopic sinus surgery, number of previous endoscopic sinus surgery, concomitant asthma, history of an allergic condition, immunoglobulin E (IgE), allergy to nonsteroidal anti-inflammatory drugs (NSAIDs), Aspirin Exacerbated Respiratory Disease (AERD), other comorbidities associated, blood eosinophils, nasal polyp score, sinonasal outcome test 22 (SNOT 22), sniffin' stick test, the start date of dupilumab therapy and number of doses of dupilumab and eventually, Dupilumab's adverse events related to administration. The Wilcoxon test for dependent samples was performed to compare variables. Statistical significance was assumed for p values < 0.05. A statistically significant reduction in SNOT-22 and NPS was shown at the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). A statistically significant increase value at the Sniffin' sticks test was shown in the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). At the 12-month follow-up, according to EUFOREA indications, all patients were considered to remain in treatment with dupilumab and continued the treatment because of a reduced NPS, improved quality of life and a reduced need for system corticosteroids. Dupilumab seemed to be well tolerated by all patients. Any adverse effect of the drug led to the quit of biological treatment. This multi-centric real-life study supported the effectiveness of dupilumab as an add-on therapy to intranasal corticosteroids in patients with severe uncontrolled CRSwNP in improvement of quality of life, severity of symptoms, polyp size reduction and smell function. Furthermore, our data support the safety profile of monoclonal therapy with dupilumab.


Cell adhesion molecule expression on CD34+ cells in grafts and time to myeloid and platelet recovery after autologous stem cell transplantation.
The relationship between cell adhesion receptor expression on CD34+ cells in stem cell grafts and the time to neutrophil and platelet recovery after autologous stem cell transplantation (ASCT [n = 25]) was studied with granulocyte/monocyte-colony stimulating factor (GM-CSF)-mobilized peripheral blood stem cells (PBSCs) and steady-state bone marrow (BM) harvests. Cell adhesion receptor expression was analyzed using flow cytometry after CD34+ cell enrichment. Significantly higher expression of L-selectin and CD44, and significantly lower expression of VLA-4, LFA-1, ICAM-1, Sialyl Lewis(x), Sialyl Lewis(A), and Thy-1 were observed on PBSCs compared with BM CD34+ cells. The log of the number of reinfused CD34+ cells, colony forming units granulocyte/macrophage (CFU-GM), and CD34+ cells coexpressing VLA-4, VLA-5, LAF-1, Mac-1, LFA-3, or CD38 but not ICAM-1, Sialyl Lewis(x), Sialyl Lewis(A), or Thy-1 correlated with the time required to reach an absolute neutrophil count (ANC) of > or =0.5 x 10(9)/L. In addition, the log of the number of CD34+ L-selectin+ and CD34+CD44+ cells reinfused after ASCT correlated better with the time required to reach an ANC of > or =0.5 x 10(9)/L than did the log of the number of CD34+ cells or CFU-GM reinfused. The log of the number of reinfused CD34+ cells, CFU-GM, and CD34+ cells coexpressing CD44, L-selectin, VLA-5 Mac-1, or CD38, but not VLA-4, LAF-1, ICAM-1, LAF-3, Sialyl Lewis(X), Sialyl Lewis(A), or Thy-1, correlated with the time required to reach a platelet count of >20 x 10(9)/L. Thus, L-selectin or CD44 may play an important role in the homing of progenitors after ASCT. In addition, the higher proportion of CD34+L-selectin+ or CD34+CD44+ cells in leukapheresis products may provide one explanation for the more rapid hematologic reconstitution observed after PBSC transplantation.


Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule.
Nanostructured lipid carriers (NLCs) were employed to formulate a lipophilic drug into hydrophilic polymeric microneedles (MNs). Hyaluronic acid (HA) was selected as a hydrophilic and bioerodible polymer to fabricate MNs, and nile red (NR) was used as a model lipophilic molecule. NR-loaded NLCs were consolidated into the HA-based MNs to prepare NLC-loaded MNs (NLC-MNs). A dispersion of NLCs was prepared by high-pressure homogenization after dissolving NR in Labrafil and mixing with melted Compritol, resulting in 268 nm NLCs with a polydispersity index of 0.273. The NLC dispersion showed a controlled release of NR over 24 hours, following Hixson-Crowell's cube root law. After mixing the NLC dispersion with the HA solution, the drawing lithography method was used to fabricate NLC-MNs. The length, base diameter, and tip diameter of the NLC-MNs were approximately 350, 380, and 30 μm, respectively. Fluorescence microscopic imaging of the NLC-MNs helped confirm that the NR-loaded NLCs were distributed evenly throughout the MNs. In a skin permeation study performed using a Franz diffusion cell with minipig dorsal skin, approximately 70% of NR was localized in the skin after 24-hour application of NLC-MNs. Confocal laser scanning microscopy (z-series) of the skin at different depths showed strong fluorescence intensity in the epidermal layer, which appeared to spread out radially with the passage of time. This study indicated that incorporation of drug-loaded NLCs into MNs could represent a promising strategy for controlled dermal delivery of lipophilic drugs.


Using raptors as environmental sentinels: monitoring the white-tailed sea eagle Haliaeetus albicilla in Sweden.
This paper summarizes results from the monitoring of reproduction of white-tailed sea eagle in Sweden 1965-2006. Since 1989 the eagle population on the Swedish Baltic coast has been included in the National Environment Monitoring Program as an indicator species for potentially harmful chemicals. The percentage of successfully reproducing pairs and nestling brood size decreased in synchrony with rising concentrations of contaminants in the 1950s on into the 1970s. Mean productivity was 1.3 young per pair prior to 1950 and decreased to 0.3 in 1965-1985. Dichlorodiphenyldichloroethene (DDE) in eagle eggs decreased from a range of annual means in 1965-1974 of 600-1200 microg g(-1) (lipid weight) to 60-140 microg g(-1) in 1996-2005. Total polychlorinated biphenyl (PCB) concentrations averaged above 1000 microg g(-1) into the early 1980s and remained in the range of 250-500 microg g(-1) in 1996-2005. Productivity began to improve when concentrations of DDE and PCBs dropped below approximately 300 and 800 microg g(-1), respectively. Brood size remains below the pre-1950 level in one coastal region, indicating a possible impact from other contaminants. The power to detect significant trends under the program is presented and discussed: if white-tailed sea eagle reproduction had been monitored earlier during the 20th century, the negative impact of dichlorodiphenyltrichloroethane (DDT, source of DDE) would have been signaled as early as the 1950s in the Baltic Sea. The dramatic fall of white-tailed sea eagle reproduction under the influence of DDT and PCBs, and the subsequent rise following their ban, illustrates the usefulness of raptors like sea eagles as sentinels for environmental pollutants.


A novel, plasmid-based system for studying gene rearrangements in mammalian cells.
We have developed a plasmid-based system for isolating gene rearrangements in mammalian cells by selection for reversion of a promoterless drug resistance gene. pNH4 contains the selectable marker gene neo under the control of the herpes simplex virus, thymidine kinase (tk) promoter and, upstream and in the opposite orientation, a dormant promoterless hygromycin B resistance gene (hph) that can be expressed following rearrangement events. An NIH 3T3 cell line stably transfected with pNH4 that has a spontaneous frequency of generation of Hphr colonies of approximately 10(-8) was isolated. Treatment of this line with ethyl methanesulfonate raised the frequency of Hphr colony formation approximately 100-fold. Approximately 60% (21 of 35) of ethyl methanesulfonate-induced Hphr clones showed rearrangements detectable by Southern blot analysis within a 40-kb region surrounding the integrated construct, including a nonhomologous recombination event and, possibly, a large insertion. Additionally, three Hphr clones showed evidence of gene amplification. Northern (RNA) blot analysis of hph mRNA suggests that the rearrangements may provide a function that allows the tk promoter to initiate transcription off the opposite strand, thus yielding hph transcripts. Cell lines harboring pNH4, or modifications of it, may be valuable for studying recombination mechanisms responsible for the various types of genetic rearrangements found in cancer cells.


Lack of Evidence That Selenium-Yeast Improves Chicken Health and Modulates the Caecal Microbiota in the Context of Colonization by Campylobacter jejuni.
Faced with ever-increasing demand, the industrial production of food animals is under pressure to increase its production. In order to keep productivity, quality, and safety standards up while reducing the use of antibiotics, farmers are seeking new feed additives. In chicken production, one of these additives is selenium. This element is expected to confer some advantages in terms of animal health and productivity, but its impact on chicken intestinal microbiota as well as on the carriage of foodborne pathogens is unknown. In this study, chickens raised in a level 2 animal facility were fed or not 0.3 ppm of in-feed selenium-yeast until 35 days of age and were inoculated or not with the foodborne pathogen Campylobacter jejuni at the age of 14 days. At the end of the study, body weight, seric IgY, intestinal IgA, seric gluthatione peroxydase activity, the caecal microbiota (analyzed by MiSeq 16S rRNA gene sequencing), and C. jejuni caecal levels were analyzed. The experiment was completely replicated twice, with two independent batches of chickens. This study revealed that, for healthy chickens raised in very good hygienic conditions, selenium-yeast does not influence the bird's body weight and lowers their seric gluthatione peroxidase activity as well as their intestinal IgA concentrations. Furthermore, selenium-yeast did not modify the caecal microbiota or the colonization of C. jejuni. The results also showed that C. jejuni colonization does not impact any of the measured chicken health parameters and only slightly impacts the caecal microbiota. This study also clearly illustrated the need for true biological replication (independent animal trials) when assessing the microbiota shifts associated with treatments as the chickens microbiotas clearly clustered according to study replicate.


Contribution of preoperative ultrasound-guided implantation of a magnetic seed for optimal localization and resection of vulvar angiosarcoma: A case report.
Vulvar cancer is a rare cause of malignancy among women. It is key for surgeons to achieve negative resection margins, as it greatly impacts patient's prognosis. Unfortunately, additional surgical procedures are often performed due to the regional anatomical complexity. Based on non-palpable breast tumors, where image-guided preoperative localization tools have enhanced the complete resection rates, we aimed at evaluating the feasibility of magnetic seed technique for localizing perineal lesions. We present the case of a 40-year-old female patient, who underwent iterative resections for a recurrent epithelioid angiosarcoma of the left labia major. Imaging revealed a suspicious regional involvement at 3 months of follow-up, for which another surgery was planned. We decided to target this non-palpable lesion with the Magnetic Seed technique to guide the intervention. A seed was inserted into the nodule under ultrasound guidance. Resection was then performed, with negative margins and no recurrence on last follow-up. Surgical procedures with minimal extension are recommended in vulvar cancer, to limit the aesthetic and functional complication. Unfortunately, recurrences and residual tumors remain frequent, even higher when surgical margin safety is not achieved. Many studies have suggested the benefit of image-guided localization tools in non-palpable breast tumors. By reducing the excising volume and focusing on the lesions, relapse and complications are rarer. We considered Magnetic Seed to be the most appropriated technique for perineal lesions. As for breast cancer, Magnetic Seed technique could be appropriate for non-palpable perineal lesions, optimizing resection margins with minimal procedures.


The FLEX study school-based physical activity programs - measurement and evaluation of implementation.
Increasing children's physical activity (PA) at school is critical to obesity prevention and health promotion. Implementing novel, low-cost PA programs offers potential to contribute to children's in-school PA, particularly in resource-constrained schools. This evaluation describes implementation fidelity, reach, and dose of two PA programs in the Fueling Learning through Exercise (FLEX) Study. Thirteen diverse, low-income Massachusetts elementary schools were recruited and randomized to the 100 Mile Club walking/running program (n = 7) or CHALK/Just Move classroom activity break PA program (n = 6). Intervention programs were delivered across two school years. Surveys with program champions/teachers and children, in-session measurement of children's PA by accelerometry (Actigraph GT3X) in a subset of schools, and key informant interviews were used to collect information on implementation, including fidelity, dose, reach, and sustainability, and to calculate an implementation score. Six CHALK/Just Move schools implemented the program in both years. Two schools randomized to 100 Mile Club did not implement at all, and only three schools implemented both years. Implementing schools had similar implementation scores (range = 0-3; 100 Mile Club = 2.0 vs. CHALK/Just Move = 1.9) but fidelity to core and enhanced elements differed between programs. In 100 Mile Club schools, dose of program delivered was greater than in CHALK/Just Move schools (34.9 vs. 19.7 min per week). Dose of PA received per session was also greater in 100 Mile Club schools (n = 55, 2 schools) compared with CHALK/Just Move schools (n = 160, 2 schools) (13.6 min vs. 2.7 min per session). A slightly higher proportion of eligible children participated in CHALK/Just Move compared to 100 Mile Club (54.0% vs. 31.2%). Both programs were well received by champions/teachers and students. Program implementation varied across programs and schools, and erosion in delivery was seen over the two years. However, among implementing schools, additional PA was delivered and received, and the programs were generally well-received. Although school resource issues remain barriers to implemention, this evaluation demonstrates that low-cost programs may enhance PA opportunities. Future research should evaluate how multiple programs can be implemented to increase children's PA at school. ClinicalTrials.gov Identifier: NCT02810834 . Registered May 11, 2015.


Ferrates (iron(VI) and iron(V)): environmentally friendly oxidants and disinfectants.
Iron(VI) and iron(v), known as ferrates, are powerful oxidants and their reactions with pollutants are typically fast with the formation of non-toxic by-products. Oxidations performed by Fe(VI) and Fe(V) show pH dependence; faster rates are observed at lower pH. Fe(VI) shows excellent disinfectant properties and can inactivate a wide variety of microorganisms at low Fe(VI) doses. Fe(VI) also possesses efficient coagulation properties and enhanced coagulation can also be achieved using Fe(VI) as a preoxidant. The reactivity of Fe(V) with pollutants is approximately 3-5 orders of magnitude faster than that of Fe(VI). Fe(V) can thus be used to oxidize pollutants and inactivate microorganisms that have resistance to Fe(VI). The final product of Fe(VI) and Fe(V) reduction is Fe(III), a non-toxic compound. Moreover, treatments by Fe(VI) do not give any mutagenic/carcinogenic by-products, which make ferrates environmentally friendly ions. This paper reviews the potential role of iron(VI) and iron(V) as oxidants and disinfectants in water and wastewater treatment processes. Examples are given to demonstrate the multifunctional properties of ferrates to purify water and wastewater.


Vera Peters and the conservative management of early-stage breast cancer.
During the first three quarters of the twentieth century, radical mastectomy was an accepted and common procedure in the management of patients with early stage cancer of the breast. After a lifetime of thinking about and working with patients with early-stage breast cancer, Vera Peters presented and published, in the mid-1970s, a retrospective historical case-control study that demonstrated the lack of a survival benefit for radical or modified radical mastectomy as compared with more conservative surgery with lumpectomy. In the years that followed, prospective randomized studies confirmed her findings.


Effects of nickel-oxide nanoparticle pre-exposure dispersion status on bioactivity in the mouse lung.
Nanotechnology is emerging as one of the world's most promising new technologies. From a toxicology perspective, nanoparticles possess two features that promote their bioactivity. The first involves physical-chemical characteristics of the nanoparticle, which include the surface area of the nanoparticle. The second feature is the ability of the nanoparticle to traverse cell membranes. These two important nanoparticle characteristics are greatly influenced by placing nanoparticles in liquid medium prior to animal exposure. Nanoparticles tend to agglomerate and clump in suspension, making it difficult to reproducibly deliver them for in vivo or in vitro experiments, possibly affecting experimental variability. Thus, we hypothesize that nanoparticle dispersion status will correlate with the in vivo bioactivity/toxicity of the particle. To test our hypothesis, nano-sized nickel oxide was suspended in four different dispersion media (phosphate-buffered saline (PBS), dispersion medium (DM), a combination of dipalmitoyl-phosphatidyl choline (DPPC) and albumin in concentrations that mimic diluted alveolar lining fluid), Survanta®, or pluronic (Pluronic F-68). Well-dispersed and poorly dispersed suspensions were generated in each media by varying sonication time on ice utilizing a Branson Sonifer 450 (25W continuous output, 20 min or 5 min, respectively). Mice (male, C57BL/6J, 7-weeks-old) were given 0-80 µg/mouse of nano-sized nickel oxide in the different states of dispersion via pharyngeal aspiration. At 1 and 7 d post-exposure, mice underwent whole lung lavage to assess pulmonary inflammation and injury as a function of dispersion status, dose and time. The results show that pre-exposure dispersion status correlates with pulmonary inflammation and injury. These results indicate that a greater degree of pre-exposure dispersion increases pulmonary inflammation and cytotoxicity, as well as decreases in the integrity of the blood-gas barrier in the lung.


Autism and chromosome abnormalities-A review.
The neuro-behavioral disorder of autism was first described in the 1940s and was predicted to have a biological basis. Since that time, with the growth of genetic investigations particularly in the area of pediatric development, an increasing number of children with autism and related disorders (autistic spectrum disorders, ASD) have been the subject of genetic studies both in the clinical setting and in the wider research environment. However, a full understanding of the biological basis of ASDs has yet to be achieved. Early observations of children with chromosomal abnormalities detected by G-banded chromosome analysis (karyotyping) and in situ hybridization revealed, in some cases, ASD associated with other features arising from such an abnormality. The introduction of higher resolution techniques for whole genome screening, such as array comparative genome hybridization (aCGH), allowed smaller imbalances to be detected, some of which are now considered to represent autism susceptibility loci. In this review, we describe some of the work underpinning the conclusion that ASDs have a genetic basis; a brief history of the developments in genetic analysis tools over the last 50 years; and the most common chromosome abnormalities found in association with ASDs. Introduction of next generation sequencing (NGS) into the clinical diagnostic setting is likely to provide further insights into this complex field but will not be covered in this review. Clin. Anat. 29:620-627, 2016. © 2016 Wiley Periodicals, Inc.


The effects of betaxolol hydrochloride ophthalmic solution on intraocular pressures during transient microgravity.
Intraocular pressure (IOP) has been found to increase during microgravity. After peaking in the first few hours of orbital flight, IOP slowly decreases to a level that is slightly elevated above baseline IOP's. These modest elevations in IOP do not require treatment. Just as in 1-G, a clinically significant elevation of IOP that occurred during spaceflight would require treatment. We are not aware of previous studies of the efficacy of IOP lowering agents under conditions of microgravity. This double-masked, placebo-controlled study measured the IOP's of 11 adult subjects (22 eyes) at baseline, preflight, and zero-gravity aboard the NASA KC-135 aircraft, and postflight. One eye of each of the subjects was treated with betaxolol hydrochloride ophthalmic solution 0.5%, while the contralateral eye was treated with normal saline placebo, for 7 d prior to parabolic flight. IOP's were measured by the Tono-Pen 2, a gravity independent tonometer. A modest, but statistically significant reduction of 2.4 mmHg in mean IOP was noted in betaxolol treated eyes at the time of preflight measurement. During zero-G, the mean IOP's of both betaxolol treated eyes and placebo treated eyes increased approximately 20% over preflight levels. Postflight IOP's were similar to preflight IOP's. The effect of betaxolol on the IOP of eyes treated with for 1 wk prior to exposure to microgravity was statistically significant, but may lack clinical significance in normal eyes. Further research needs to be done to determine the efficacy during microgravity of betaxolol and other agents, in subjects who have upper normal to slightly elevated IOP's at 1 G.


Satureja bachtiarica Induces Cancer Cell Death in Breast and Glioblastoma Cancer in 2D/3D Models and Suppresses Breast Cancer Stem Cells.
Overcoming drug resistance and specifically targeting cancer stem cells (CSCs) are critical challenges in improving cancer therapy. Nowadays, the use of novel and native medicinal plants can provide new sources for further investigations for this purpose. The aim of this study was to assess the potential of S. bachtiarica, an endemic plant with diverse medicinal applications, in suppressing and targeting cancer and cancer stem cells in glioblastoma and breast cancer. The effect of S. bachtiarica on viability, migration, invasion, and clonogenic potential of MDAMB-231 and U87-MG cells was assessed in both two- and three-dimensional cell culture models. Additionally, we evaluated its effects on the self-renewal capacity of mammospheres. The experimental outcomes indicated that S. bachtiarica decreased the viability and growth rate of cells and spheroids by inducing apoptosis and inhibited colony formation, migration, and invasion of cells and spheroids. Additionally, colony and sphere-forming ability, as well as the expression of genes associated with EMT and stemness were reduced in mammospheres treated with S. bachtiarica. In conclusion, this study provided valuable insights into the anti-cancer effects of S. bachtiarica, particularly in relation to breast CSCs. Therefore, S. bachtiarica may be a potential adjuvant for the treatment of cancer.


Fluid Extravasation in Hip Arthroscopy: A Systematic Review.
The purpose of this systematic review was to (1) characterize cases of fluid extravasation during hip arthroscopy and explore common factors among them and (2) describe management strategies and outcomes of this complication. The databases MEDLINE, EMBASE, and PubMed were searched and screened in duplicate. Data regarding patient demographics, fluid management, presentation, management, and outcomes were collected. Study quality was assessed in duplicate using the Methodological Index for Non-Randomized Studies Criteria. Fourteen studies (1,286 patients) were included. Twenty-two occurrences of symptomatic fluid extravasation were reported in 21 patients (1.6% of total patients; one patient had fluid extravasation during 2 separate hip arthroscopies). Two studies of normal fluid extravasation in asymptomatic patients reported 1.13 to 3.06 L of extravasated fluid observed on computed tomography. Nine case studies were included, which provided detailed patient and surgical information. Of these 9 patients (10 cases) with a mean age of 38.2 years old (range, 15 to 55 years), 6 were female. Signs of fluid extravasation included abdominal distension (89%), hypothermia (56%), hypotension. and metabolic acidosis (33% each). Four patients required surgical intervention, while 3 underwent paracentesis. Two patients were managed conservatively. All patients stabilized and were discharged, with one patient reporting abdominal complaints at latest follow-up (length of follow-up unspecified). Fluid extravasation is a rare but potentially life-threatening complication of hip arthroscopy. It is important for surgeons and anaesthesiologists to be aware of its existence in order to recognize and manage it promptly. Most patients require interventional management by surgery or paracentesis, but some stabilize with conservative management. Level IV, systematic review of Level IV studies.


Atomic stabilization by super-intense lasers.
Supercomputer simulations predict the creation of an unexpectedly stable form of atomic matter when ordinary atoms are irradiated by very intense, high-frequency laser pulses. In the rising edge of a very intense pulse of ionizing radiation, the atom's wave function distorts adiabatically into a distribution with two well-separated peaks. As the intensity increases, the peak spacing increases so that the atomic electron spends more time far from the nucleus and the ionization rate decreases. This leads to the surprising and counter-intuitive result that the atom becomes more stable as the ionizing radiation gets stronger.


Initial experience with single-incision laparoscopic cholecystectomy.
Single-incision laparoscopic surgical procedures are being developed with the goal of improving cosmesis, reducing postoperative pain, and increasing patient satisfaction. We performed this study to evaluate our initial experience with single-incision laparoscopic cholecystectomy. We used an infraumbilical incision with two upper low-profile 5-mm ports and one lower standard 5-mm port and either a standard 30 degrees Storz laparoscope or an Olympus deflectable tip laparoscope. All patients were followed postoperatively to evaluate the feasibility and outcomes of the procedure. A total of 60 gallbladders were successfully removed by this method (95.2% success rate). Three cases were converted to standard laparoscopic cholecystectomy (4.8% conversion rate) with no conversion to open cholecystectomy. There were no major complications (bile duct injury, liver injury, bowel injury, biliary leak). Median operative time was 51 +/- 21 minutes. Diagnoses included cholelithiasis (55%), biliary dyskinesia (32%), biliary colic (13%), and one case of gangrenous cholecystitis. Median patient age was 47 years with a strong female predominance (87%). Our initial experience demonstrates that single-incision laparoscopic cholecystectomy is effective and safe. We are confident that single-incision laparoscopic cholecystectomy is a viable alternative to standard laparoscopic cholecystectomy.


Resource Allocation and Decision Making for Pediatric and Congenital Cardiac Catheterization During the Novel Coronavirus SARS-CoV-2 (COVID-19) Pandemic: A U.S. Multi-Institutional Perspective.
The novel coronavirus (COVID-19) pandemic has placed severe stress on healthcare systems around the world. There is limited information on current practices in pediatric cardiac catheterization laboratories in the United States (US). To describe current practice patterns and make recommendations regarding potential resource allocation for congenital cardiac catheterization during the COVID-19 pandemic. A web-based survey was distributed regarding case candidacy and catheterization laboratory preparedness. Centers were categorized based on the current degree of disease burden in that community (as of April 1, 2020). Data and consensus opinion were utilized to develop recommendations. Respondents belonged to 56 unique US centers, with 27 (48.2%) located in counties with a high number of COVID-19 cases. All centers have canceled elective procedures. There was relative uniformity (>88% agreement) among centers as to which procedures were considered elective. To date, only three centers have performed a catheterization on a confirmed COVID-19 positive patient. Centers located in areas with a higher number of COVID-9 cases have been more involved in a simulation of donning and doffing personal protective equipment (PPE) than low-prevalence centers (46.7% vs 10.3%, respectively; P<.001). Currently, only a small fraction of operators has been reassigned to provide clinical services outside their scope of practice. At this stage in the COVID-19 pandemic, pediatric/congenital catheterization laboratories have dramatically reduced case volumes. This document serves to define current patterns and provides guidance and recommendations on the preservation and repurposing of resources to help pediatric cardiac programs develop strategies for patient care during this unprecedented crisis.


[Self-efficacy among doctors in hospitals after a course in clinical communication].
There is a paucity of research on clinical communication in hospitals. A large Norwegian hospital has tried out a course (developed in the USA) in clinical communication. In this substudy, we investigated the association between doctors' self-efficacy and participation in this course. Doctors under 60 years of age, working in clinical somatic departments in Akershus University Hospital, were eligible for inclusion. The participants completed a validated questionnaire before and after the course. Self-efficacy was assessed (on a 10-point scale) through nine important communication skills. 103 doctors (randomly selected) were asked to participate in the study; 62 of them completed the 20-hour course. After completion of the course, the participants were more confident that communication skills could be learnt in this way than they were before it started. Their self-efficacy only improved moderately, on average 0.6 on the 10-point scale, but the change was statistically significant for seven of the nine skills. After completion of the course, self-efficacy had improved for 41 doctors and deteriorated for ten. Nevertheless, the latter were still positive regarding the learning effect of the course. The effects were independent of the doctors' sex, age, position (resident or consultant), self-efficacy before the course, and specialty. Of the skills taught, demonstration of empathy was the one that fewest doctors wanted to practice after the course. A short course in clinical communication skills led to a moderate improvement in the participating doctors' self-efficacy. Whether this change implies improved communication is currently under investigation.


The Quality of Life of Patients Living with a Urinary Catheter and Its Associated Factors: A Cross-Sectional Study in Egypt.
In Arabic countries, no research has focused on the experience of patients with indwelling urinary catheters. This cross-sectional study is the first to evaluate the catheter-specific quality of life (QoL) of patients living with a urinary catheter in Egypt. This study was conducted from April to September 2017, using a convenience sample of patients from a University Hospital. Data were collected using the International Consultation on Incontinence Questionnaire-Long-Term Catheter QoL (ICIQ-LTCQoL) instrument, along with a demographic datasheet. 141 were enrolled, with 47.5% inpatients, 52.5% outpatients. A total of 70.9% reported problems with catheter function, and 92.2% reported that the catheter affected their daily lives. Place (inpatient or outpatient) was significantly associated with the total score of the ICIQ-LTCQoL (mean difference (MD) 6.34 (95% CI: 3.0 to 9.73)) and both subscales (catheter function subscale: MD = 4.92 (95% CI: 2.12 to 7.73) and lifestyle impact subscale: MD = 1.44 (95% CI: 0.3 to 2.63)), suggesting that outpatients have poorer QoL than inpatients. Moreover, catheter material was significantly related to the catheter function domain with Silicone Foley Catheter (100% Silicon) users experiencing poorer QoL related to catheter function than those with Latex Foley Catheter (Silicon-coated) (MD 4.43 (95% CI: 0.62 to 8.24). Workers/employees were found to have poorer QoL than those who were retired (MD = 4.94 (95% CI: 0.3 to 9.63)). The results highlight the necessity of assessing function and concern regarding urinary catheter use and its impact on QoL, as well as its determinants. Evidence-based educational programs should be designed to enhance patients' self-care abilities to relieve their sense of distress and enhance their confidence in caring for their catheters.


[The ecophysiology of Agama mutabilis Merren, in southern Tunisia].
The behavioural thermoregulation and rate of water turnover of the lizard Agama mutabilis were studied in southern Tunisia in summer and compared with another agamid, Amphibolurus inermis, Which occuies a similar habitat in Australia. The thermoregulatory sequence differs little between the two species although Agama mutabilis lacks a burrow and is probably more resistant to elevated body temperatures. Agama mutabilis has an extremely low rate of water turnover for such a small lizard [3,37 ml (100 g.day)-1] and ins probably, on the whole, better-adapted physiologically to desert conditions than Amphibolurus inermis.


Characterizing both bacteria and fungi improves understanding of the Arabidopsis root microbiome.
Roots provide plants mineral nutrients and stability in soil; while doing so, they come into contact with diverse soil microbes that affect plant health and productivity. Despite their ecological and agricultural relevance, the factors that shape the root microbiome remain poorly understood. We grew a worldwide panel of replicated Arabidopsis thaliana accessions outdoors and over winter to characterize their root-microbial communities. Although studies of the root microbiome tend to focus on bacteria, we found evidence that fungi have a strong influence on the structure of the root microbiome. Moreover, host effects appear to have a stronger influence on plant-fungal communities than plant-bacterial communities. Mapping the host genes that affect microbiome traits identified a priori candidate genes with roles in plant immunity; the root microbiome also appears to be strongly affected by genes that impact root and root hair development. Our results suggest that future analyses of the root microbiome should focus on multiple kingdoms, and that the root microbiome is shaped not only by genes involved in defense, but also by genes involved in plant form and physiology.


Comparative biochemical and ultrastructural studies of capillaries from normal humans, normal mice, and human cerebral astrocytomas.
Capillaries from cerebral white matter were isolated from normal humans and normal mice and from human astrocytomas (Grades II-IV) to investigate potential biochemical and ultrastructural differences between normal and neoplastic-derived microvessels. Capillaries from Grade III and IV astrocytomas averaged 55-fold higher in the concentration of total protein than capillaries from normal mouse and normal human cerebral tissues. Scanning electron microscopic examination revealed more bifurcations and fewer surface undulations in the capillaries derived from anaplastic astrocytomas than in capillaries derived from normal specimens. Sprouting configurations were detected in the capillaries from anaplastic astrocytomas. They measured 4 to 5 micron in diameter and manifested fewer surface undulations than capillaries from normal human white matter. The results of these preliminary investigations suggest early capillary growth from parent vessels in high-grade and highly vascularized astrocytomas.


Human health and performance for long-duration spaceflight.
Future long-duration spaceflights are now being planned to the Moon and Mars as a part of the "Vision for Space Exploration" program initiated by NASA in 2004. This report describes the design reference missions for the International Space Station, Lunar Base, and eventually a Mars Expedition. There is a need to develop more stringent preflight medical screening for crewmembers to minimize risk factors for diseases which cannot be effectively treated in flight. Since funding for space life sciences research and development has been eliminated to fund program development, these missions will be enabled by countermeasures much like those currently in use aboard the International Space Station. Artificial gravity using centrifugation in a rotating spacecraft has been suggested repeatedly as a "universal countermeasure" against deconditioning in microgravity and could be an option if other countermeasures are found to be ineffective. However, the greatest medical unknown in interplanetary flight may be the effects of radiation exposure. In addition, a Mars expedition would lead to a far greater level of isolation and psychological stress than any space mission attempted previously; because of this, psychiatric decompensation remains a risk. Historically, mortality and morbidity related to illness and injury have accounted for more failures and delays in new exploration than have defective transportation systems. The medical care system on a future Mars expedition will need to be autonomous and self-sufficient due to the extremely long separation from definitive medical care. This capability could be expanded by the presence of a physician in the crew and including simple, low-technology surgical capability.


Structure of solidified colloidal array laser filters studied by cryogenic transmission electron microscopy.
Ordered arrays of charged uniform colloidal polystyrene particles in solution form a single-wavelength laser filter that is transparent to other wavelengths. A usable filter was prepared by solidification within an acrylamide-methylene-bisacrylamide gel. The rejection wavelength of the colloidal array filter changes with gel composition. Cryogenic transmission electron microscopy of two gel formulations shows that the colloidal array filter is composed of AAA stacking of close-packed planes. Excellent agreement is found between the layer spacings measured and those predicted from the rejection wavelengths.


Advances in male hormonal contraception.
Contraception is a basic human right for its role on health, quality of life and wellbeing of the woman and of the society as a whole. Since the introduction of female hormonal contraception the responsibility of family planning has always been with women. Currently there are only a few contraceptive methods available for men, but recently, men have become more interested in supporting their partners actively. Over the last few decades different trials have been performed providing important advances in the development of a safe and effective hormonal contraceptive for men. This paper summarizes some of the most recent trials.


Hypopharyngeal and oesophageal foreign bodies.
Foreign bodies in the food passages are quite common in Jos Community. Majority of 119 cases seen over a period of four years were children 92.4% and a coin was the commonest foreign body (86.5%). The site of lodgement of the foreign body was hypopharynx and abdomen in 11 cases each while 97 were held in oesophagus, mainly in its upper part. Removal of the foreign body by oesophagoscopy was difficult in patients who presented late. The coins formed a pouch in posterior oesophageal wall in six cases while their anterior surfaces got discoloured in 14 cases causing difficulty in their identification. Besides coins in children and dentures in adults, nine patients accidently swallowed a wide variety of foreign objects of different shapes and sizes. Management of such cases has been discussed.


Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells.
In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These results suggest that SCD1 is a critical target in lung cancer tumor-initiating cells.


Ecological and pest-management implications of sex differences in scarab landing patterns on grape vines.
Melolonthinae beetles, comprising different white grub species, are a globally-distributed pest group. Their larvae feed on roots of several crop and forestry species, and adults can cause severe defoliation. In New Zealand, the endemic scarab pest Costelytra zealandica (White) causes severe defoliation on different horticultural crops, including grape vines (Vitis vinifera). Understanding flight and landing behaviours of this pest can help inform pest management decisions. Adult beetles were counted and then removed from 96 grape vine plants from 21:30 until 23:00 h, every day from October 26 until December 2, during 2014 and 2015. Also, adults were removed from the grape vine foliage at dusk 5, 10, 15, 20 and 25 min after flight started on 2015. Statistical analyses were performed using generalised linear models with a beta-binomial distribution to analyse proportions and with a negative binomial distribution for beetle abundance. By analysing C. zealandica sex ratios during its entire flight season, it is clear that the proportion of males is higher at the beginning of the season, gradually declining towards its end. When adults were successively removed from the grape vines at 5-min intervals after flight activity begun, the mean proportion of males ranged from 6-28%. The male proportion suggests males were attracted to females that had already landed on grape vines, probably through pheromone release. The seasonal and daily changes in adult C. zealandica sex ratio throughout its flight season are presented for the first time. Although seasonal changes in sex ratio have been reported for other melolonthines, changes during their daily flight activity have not been analysed so far. Sex-ratio changes can have important consequences for the management of this pest species, and possibly for other melolonthines, as it has been previously suggested that C. zealandica females land on plants that produce a silhouette against the sky. Therefore, long-term management might evaluate the effect of different plant heights and architecture on female melolonthine landing patterns, with consequences for male distribution, and subsequently overall damage within horticultural areas.


Clinical Outcomes of Acid Suppressive Therapy Use in Hematology/Oncology Patients at an Academic Medical Center.
Acid suppressive therapy (AST)-namely, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs)-is routinely prescribed to hospitalized patients for stress ulcer prophylaxis (SUP). To identify the incidence of and indications for AST use in the hematology/oncology population as well as to identify the occurrence of the following PPI-associated adverse events: pneumonia and Clostridium difficile-associated diarrhea (CDAD). A retrospective chart review was conducted on adult hematology/oncology patients admitted to any oncology service for ≥48 hours from October 1, 2014, to December 31, 2014. Of the 298 patients who met the inclusion criteria, 73% (n = 218) received an AST during admission. The most common indication for an AST was SUP (63%). The incidence of hospital-acquired pneumonia (HAP) was 10%, 0%, and 4% in patients who received a PPI, H2RA, and no AST, respectively (14/142 vs 0/70 vs 3/80; odds ratio [OR] for PPI vs no AST = 2.68; 95% CI = 0.75-9.63). The incidence of CDAD was 3%, 1.3%, and 1.2% in patients who received a PPI, H2RA, and no AST, respectively (4/142 vs 1/70 vs 1/80; OR for PPI vs H2RA = 1.92; 95% CI = 0.21-17.47). This is the first study to describe the incidence of and indications for AST use in the hospitalized hematology/oncology population. There was a high occurrence of AST use, particularly PPIs, in these patients at our institution. Additionally, there was a trend toward an increased risk of HAP and CDAD in patients who received AST during admission.


Selection of CTL escape mutants in mice infected with a neurotropic coronavirus: quantitative estimate of TCR diversity in the infected central nervous system.
Variant viruses mutated in the immunodominant cytotoxic T cell epitope surface (S) glycoprotein S-510-518 are selected in mice chronically infected with mouse hepatitis virus, strain JHM. We determined whether this selection occurred in the presence of an oligoclonal or polyclonal T cell response using soluble MHC/peptide tetramers in direct ex vivo analyses of CNS-derived lymphocytes. A total of 42% (range, 29-60%) of CD8 T cells in the CNS of mice with acute encephalitis recognized epitope S-510-518. A total of 34% (range, 18-62%) of cells from mice with hind limb paralysis (and chronic demyelination) were also epitope specific, even though only virus expressing mutated epitope is detected in these animals. Sequence analysis of the beta-chain CDR3 of 487 tetramer S-510-518-positive cDNA clones from nine mice showed that a majority of clonotypes were identified in more than one mouse. From these analyses, we estimated that 300-500 different CD8 T cell clonotypes responsive to epitope S-510-518 were present in each acutely infected brain, while 100-900 were present in the CNS of each mouse with chronic disease. In conclusion, a polyclonal CD8 T cell response to an epitope does not preclude the selection of T cell escape mutants, and epitope-specific T cells are still present at high levels even after RNA-encoding wild-type sequence is no longer detectable.


Mechanisms of Antioxidant Resistance in Different Wheat Genotypes under Salt Stress and Hypoxia.
Various stressors lead to an increase in ROS and damage to plant tissues. Plants have a powerful antioxidant system (AOS), which allows them to neutralize excess ROS. We detected an intense fluorescent glow of ROS in the cells of the cap, meristem, and elongation zones in the roots of wheat Triticum aestivum (Orenburgskaya 22 variety) and Triticum durum (Zolotaya variety). An increase in ROS was accompanied by DNA breaks in the nuclei of wheat root cells, the release of cytochrome c from mitochondria into the cytoplasm, and the translocation of phosphatidylserine into the outer layer of the plasma membrane under salt stress and hypoxia. The different resistances of the two wheat varieties to different abiotic stresses were revealed. The soft wheat variety Orenburgskaya 22 showed high resistance to salt stress but sensitivity to hypoxia, and the durum wheat variety Zolotaya showed tolerance to hypoxia but high sensitivity to salt stress. Different activations of AOS components (GSH, MnSOD, Cu/ZnSOD, CAT, PX, GPX, and GST) were revealed in different wheat genotypes. The basis for the tolerance of the Zolotaya variety to hypoxia is the high content of glutathione (GSH) and the activation of glutathione-dependent enzymes. One of the mechanisms of high resistance to salt stress in the Orenburgskaya 22 variety is a decrease in the level of ROS as a result of the increased activity of the MnSOD and Cu/ZnSOD genes. Identifying the mechanisms of plant tolerance to abiotic stress is the most important task for improving breeding varieties of agricultural plants and increasing their yield.


Adding Surgical Edge-to-Edge Mitral Valve Repair to Myectomy in Hypertrophic Obstructive Cardiomyopathy: Long-Term Functional and Echocardiographic Outcome.
This study evaluates the early and long-term clinical and echocardiographic outcome of edge-to-edge (E2E) mitral valve repair (MVr) concomitant to septal myectomy (SM) in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). A retrospective single-center analysis was performed of patients who underwent isolated SM or SM with E2E MVr from 2011 to 2022. Exclusion criteria were primary mitral valve (MV) disease or concomitant valve surgery. Early and long-term safety, functional and echocardiographic outcomes were compared between groups. Between January 2011 and April 2022, 76 consecutive patients underwent SM for HOCM: 42 patients (55%) underwent SM without additional E2E MVr (Group 1) and 34 patients (45%) underwent SM with additional E2E MVr (Group 2). At latest follow-up, 87% of patients were in New York Heart Association (NYHA) class I-II with no significant differences in NYHA class between groups. Incidence of safety events was comparable between groups. Echocardiographic relief of left ventricular outflow tract (LVOT) obstruction was comparable at early follow-up (P = 0.68), with a significant but small difference in maximum LVOT pressure gradient at latest follow-up in favor of E2E MVr (P = 0.04). Furthermore, patients who underwent SM with E2E MVr showed less residual systolic anterior motion at early and latest follow-up (P = 0.020; P = 0.178). Reintervention on the MV was absent in both groups at 1 year and equally low at follow-up (P = 0.27). This study demonstrates that adding E2E MVr to septal myectomy is as safe as isolated myectomy for the treatment of HOCM. Moreover, the addition of E2E MVr is associated with similar excellent functional improvement and freedom from MV reintervention.


[Trends in mortality from homicide in Medellín (Colombia): 1975-2003].
To describe and evaluate homicide mortality trends in the city of Medellin, Colombia, between 1975 and 2003. Deaths from homicide between January, 1975 and December, 2003 were studied. With the aid of the SSS1 program, an analysis of temporary series was run using iterative procedures for ARIMA model construction. The mean monthly homicide mortality rate was 13.2 x 10(5) (minimum 1.94 February 1977 and maximum 38.78 December 1992). A peak was observed in the central period of the series. Several models were studied and an ARIMA (0,1,1)(0,0,1)12 model was selected. Marked annual seasonal variation was found in mortality from homicide in the city of Medellín. The highest rates were found in the month of December.


High throughput phenotyping dataset related to seed and seedling traits of sugar beet genotypes.
Several seed and seedling traits are measured to evaluate germination and emergence potential in relation with environmental conditions. More generally, these traits are also measured in the field of ecology as simple traits that can be correlated to other adaptative traits more difficult to measure on adult plants, as for example traits of the rooting system. Methods were developed for deep high throughput phenotyping of hundreds of genotypes from dry seed to the end of heterotrophic growth. The present dataset comes from a project on genotyping and phenotyping of populations of genotypes, with different geographic and genetic origins so as to increase genotypic diversity of sugar beet in terms of germination and early growth traits, evaluated at low temperatures. Data were collected in relation to the creation of the first sugar beet crop ontology. This dataset corresponds to the first automated phenotyping of a population of 198 genotypes and 4 commercial control varieties and is hosted on INRAE public depository under the reference number doi.org/10.15,454/AKNF4Q. The equipment and methods presented here are available on a phenotyping platform opened to collaborative research and adaptable for specific services for characterizing thousands of genotypes on different crops or other species. The phenotyping values can also be linked to genomic information to study the genetic determinism of the trait values.


Neighbors, friends, and other nonkin caregivers of community-living dependent elders.
To describe naturally occurring care relationships between unpaid, nonprofessional, nonkin (unrelated) caregivers and frail community-living older adults. Face-to-face, semistructured interviews were conducted with a convenience sample of 114 caregivers and care recipients recruited from the community through a variety of organizations. Standard techniques for thematic analysis of qualitative data were used along with descriptive and other statistics as appropriate for numerate data. Nonkin caregiving proved to be heterogeneous in initiation of relationship, form, duration, tasks performed, and association with family caregivers. Partnerships ranged from 0.1 to 57 years in duration, with just over half (58%) starting with the provision of care. Many caregivers (47%) were themselves older adults, aged 65 or older. There was little variation in what motivated or rewarded caregivers, many of whom felt morally obligated to help. More than half the sample used kin terms to characterize their relationship. Four distinct styles of relationship were discerned, varying by degree of emotional intimacy and types of assistance given. All relationships, however, involved socializing and help with at least two instrumental tasks of daily life. This kind of caregiving is important for sustaining community living for about 10% of frail elderly persons. A greater understanding is needed, from both theoretical and practical perspectives, of when and how nonkin relationships are beneficial and why they in many ways successfully mirror the actions and sentiments of family caregivers.


Aspects of Coding in Canada: Through the Eyes of an Australian HIM.
For the purpose of this brief update report, the author (an Australian Health Information Manager currently working in Canada) was asked to select certain aspects of the current coding system in Canada that she believes highlight relevant differences between the Canadian and Australian systems, on the assumption that this might be of interest to other Australian HIMs. The author has provided a brief overview of some recent changes to the Canadian classification system (e.g. new electronic product replacing coding books), as well a focus on some aspects of coder training and coding studies as seen through the eyes of an Australian HIM.


Data needs for B-24 and beyond: NHANES data relevant for nutrition surveillance of infants and young children.
The period from birth to 24 mo (B-24) is a critical phase in which nutrient requirements for growth and development are high and several transitions in food consumption practices occur. A few large-scale national studies (eg, the Feeding Infants and Toddlers Study and Infant Feeding Practices Study) offer important insights into infant feeding practices and food consumption patterns in young children in the United States. The NHANES collects comprehensive cross-sectional data on the nutrition and health of Americans including infants and toddlers. This article describes the NHANES program and data from NHANES 1999-2010 on young children that are relevant for the B-24 Project. NHANES is a nationally representative survey of the noninstitutionalized US population that combines personal interviews with standardized physical examination and measurements via mobile examination centers. Data on infant feeding practices (breastfeeding and timing of introduction and nature of complementary foods), dietary intake (two 24-h recalls), and nutrient supplements are collected. Data on demographic characteristics, anthropometric measurements, biomarkers of nutrient status, food security, and participation in federal nutrition programs are also available. Data can be accessed online, downloaded, and pooled over several survey cycles, allowing examination of infant feeding practices, food and nutrient intakes, and nutritional status of Americans <2 y old. Subgroup analyses by race-ethnicity and income status are also possible. NHANES responds to evolving data needs, as feasible, in the context of the survey design, research priorities, and funding. It offers a vehicle for potentially gathering additional data on children <2 y to address the objectives of the B-24 Project in the future.


Self esteem and organizational commitment among health information management staff in tertiary care hospitals in Tehran.
Self esteem (SE) and organizational commitment (OC)? have significant impact on the quality of work life. This study aims to gain a better understanding of the relationships between SE and OC among health information management staff in tertiary care hospitals in Tehran (Iran). This was a descriptive correlational and cross sectional study conducted on the health information management staff of tertiary care hospitals in Tehran, Iran. A total of 155 participants were randomly selected from 400 staff. Data were collected by two standard questionnaires. The SE and OC was measured using Eysenck SE scale and Meyer and Allen's three component model, respectively. The collected data were analyzed with the SPSS (version 16) using statistical tests of of independent T-test, Pearson Correlation coefficient, one way ANOVA and F tests. The OC and SE of the employees' were 67.8?, out of 120 (weak) and 21.0 out of 30 (moderate), respectively. The values for affective commitment, normative commitment, and continuance commitment were respectively 21.3 out of 40 (moderate), 23.9 out of 40 (moderate), and 22.7 out of 40 (moderate). The Pearson correlation coefficient test showed a significant OC and SE was statistically significant (P<0.05). The one way ANOVA test (P<0.05) did not show any significant difference between educational degree and work experience with SE and OC. This research showed that SE and OC ?are moderate. SE and OC have strong correlation with turnover, critical thinking, job satisfaction, and individual and organizational improvement. Therefore, applying appropriate human resource policies is crucial to reinforce these measures.


Chicoric acid induces apoptosis in 3T3-L1 preadipocytes through ROS-mediated PI3K/Akt and MAPK signaling pathways.
Chicoric acid has been reported to possess various bioactivities. However, the antiobesity effects of chicoric acid remain poorly understood. In this study, we investigated the effects of chicoric acid on 3T3-L1 preadipocytes and its molecular mechanisms of apoptosis. Chicoric acid inhibited cell viability and induced apoptosis in 3T3-L1 preadipocytes which was characterized by chromatin condensation and poly ADP-ribose-polymerase (PARP) cleavage. Mitochondrial membrane potential (MMP) loss, Bax/Bcl-2 dysregulation, cytochrome c release, and caspase-3 activation were observed, indicating mitochondria-dependent apoptosis induced by chicoric acid. Furthermore, PI3K/Akt and MAPK (p38 MAPK, JNK, and ERK1/2) signaling pathways were involved in chicoric acid-induced apoptosis. The employment of protein kinase inhibitors LY294002, SB203580, SP600125, and U0126 revealed that PI3K/Akt signaling pathway interplayed with MAPK signaling pathways. Moreover, chicoric acid induced reactive oxygen species (ROS) generation. Pretreatment with the antioxidant N-acetylcysteine (NAC) significantly blocked cell death and changes of Akt and MAPK signalings induced by chicoric acid. In addition, chicoric acid down regulated HO-1 and COX-2 via the PI3K/Akt pathway.


Significance of the hepatitis C virus core antigen testing as an alternative marker for hepatitis diagnosis in Egyptian patients.
Hepatitis C virus (HCV) core antigen (Ag) quantification by enzyme-immunoassays has been proposed as an economic and simpler alternative to HCV RNA detection. The current study was undertaken to assess the significance of HCV core antigen assay for the diagnosis of chronic HCV infection and monitoring response to antiviral therapy in Egyptian patients. Sixty three HCV antibody positive patients and ten interferon-treated patients were included in the current study. The included patients were divided according to their viral load into four groups as follows; group I (n=10): HCV RNA loads ≤ 10000 IU/ml, group II (n=20): HCV RNA loads > 10000 ≤ 100000 IU/ml, group III (n=33): HCV RNA loads >100000 IU/ml and group IV (n=10): interferon-treated HCV patients with a negative HCV RNA. Serum HCV core Ag and RNA loads were assayed and their correlations, including linear regression lines, were calculated. HCV core Ag exhibited a non-significant (p > 0.05) difference between all the studied groups. Concerning, group I patients, HCV core Ag levels and HCV RNA loads were positively correlated, with a correlation coefficient of 0.73 (p < 0.05). Group II and III showed stronger correlations; the recorded values were 0.81 (p < 0.0001) and 0.94 (p < 0.0001) for group II and III, respectively. HCV core Ag test can be used as an alternative to HCV RNA tests to evaluate chronic infection when the HCV RNA test is unavailable, but is not reliable enough for treatment monitoring.


Extracellular Ca2+ entry and Ca2+ release from inositol 1,4,5-trisphosphate-sensitive stores function at fertilization in oocytes of the marine bivalve Mytilus edulis.
An oocyte of the marine bivalve Mytilus edulis, which is arrested at metaphase I, reinitiates meiosis at fertilization. The fertilized oocyte shows increases in intracellular Ca2+ ([Ca2+]i) comprising three different phases: an initial large [Ca2+]i transient, a subsequent low but sustained [Ca2+]i elevation, and repetitive small [Ca2+]i transients. In this study, we have investigated the sources and mechanisms of the sperm-induced [Ca2+]i increases. Application of methoxyverapamil (D-600), an inhibitor of voltage-dependent Ca2+ influx, suppressed the initial [Ca2+]i transient but did not affect the following two phases of [Ca2+]i changes. Injection of heparin, an antagonist of the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the later two phases without much affecting the initial transient. Combined application of D-600 and heparin almost completely abolished the three phases of the sperm-induced [Ca2+]i changes. Furthermore, Ca2+ influx caused by seawater containing excess K+ was blocked by D-600 but not by heparin, and IP3-induced Ca2+ release caused by photolysis of injected 'caged' derivatives of IP3 was blocked by heparin but not by D-600. These results strongly suggest that two types of Ca2+ mobilization systems, the extracellular Ca2+ entry responsible for an initial [Ca2+]i transient and the IP3 receptor-mediated Ca2+ release responsible for the following two phases of [Ca2+]i changes, function at fertilization of Mytilus oocytes.


An 8-year review of operation enduring freedom and operation iraqi freedom resuscitative thoracotomies.
Appropriate indications for resuscitative thoracotomy (RT) in an austere environment continue to evolve; the aim of this study was to determine survival and to analyze demographics of survivors within U.S. military personnel undergoing RT. A retrospective review was performed of all U.S. soldiers who underwent thoracotomy in theater during Operation Iraqi Freedom and Operation Enduring Freedom. After individualized review, patients in extremis or who lost pulses and had their thoracotomy performed within 10 minutes of arrival to the emergency department were included. The primary outcome was survival at final hospital discharge, and secondary outcomes included demographics associated with survival. Between January 2003 and May 2010, 81 U.S. military personnel met inclusion criteria for RT in theater. As low as 6.7% (3/45) of patients receiving prehospital cardiopulmonary resuscitation were alive at final hospital discharge. Survival from RT after explosive/blast injury, penetrating (gunshot wound), and blunt trauma were 16.3% (8/49), 0% (0/28), and 0% (0/4), respectively. Patients with primary explosive/blast extremity trauma undergoing RT had a survival of 27.3% (6/22). Higher initial oxygen saturations, larger volume of crystalloids and blood products infused, and higher extremity abbreviated injury score were all associated with survival. Combat casualties who present pulseless or in extremis who were injured as a result of an explosive/blast injury mechanism resulting in a primary extremity injury may have a survival benefit from undergoing a RT in an austere environment.


Mediation analysis with principal stratification.
In assessing the mechanism of treatment efficacy in randomized clinical trials, investigators often perform mediation analyses by analyzing if the significant intent-to-treat treatment effect on outcome occurs through or around a third intermediate or mediating variable: indirect and direct effects, respectively. Standard mediation analyses assume sequential ignorability, i.e. conditional on covariates the intermediate or mediating factor is randomly assigned, as is the treatment in a randomized clinical trial. This research focuses on the application of the principal stratification (PS) approach for estimating the direct effect of a randomized treatment but without the standard sequential ignorability assumption. This approach is used to estimate the direct effect of treatment as a difference between expectations of potential outcomes within latent subgroups of participants for whom the intermediate variable behavior would be constant, regardless of the randomized treatment assignment. Using a Bayesian estimation procedure, we also assess the sensitivity of results based on the PS approach to heterogeneity of the variances among these principal strata. We assess this approach with simulations and apply it to two psychiatric examples. Both examples and the simulations indicated robustness of our findings to the homogeneous variance assumption. However, simulations showed that the magnitude of treatment effects derived under the PS approach were sensitive to model mis-specification.


An Improved In-house MALDI-TOF MS Protocol for Direct Cost-Effective Identification of Pathogens from Blood Cultures.
Background: Bloodstream infection is a major cause of morbidity and mortality in hospitalized patients worldwide. Delays in the identification of microorganisms often leads to a poor prognosis. The application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) directly to blood culture (BC) broth can potentially identify bloodstream infections earlier, and facilitate timely management. Methods: We developed an "in-house" (IH) protocol for direct MALDI-TOF MS based identification of organisms in positive BCs. The IH protocol was initially evaluated and improved with spiked BC samples, and its performance was compared with the commercial Sepsityper™ kit using both traditional and modified cut-off values. We then studied in parallel the performance of the IH protocol and the colony MS identifications in positive clinical BC samples using only modified cut-off values. All discrepancies were investigated by "gold standard" of gene sequencing. Results: In 54 spiked BC samples, the IH method showed comparable results with Sepsityper™ after applying modified cut-off values. Specifically, accurate species and genus level identification was achieved in 88.7 and 3.9% of all the clinical monomicrobial BCs (284/301, 94.4%), respectively. The IH protocol exhibited superior performance for Gram negative bacteria than for Gram positive bacteria (92.8 vs. 82.4%). For anaerobes and yeasts, accurate species identification was achieved in 80.0 and 90.0% of the cases, respectively. For polymicrobial cultures (17/301, 5.6%), MALDI-TOF MS correctly identified a single species present in all the polymicrobial BCs under the Standard mode, while using the MIXED method, two species were correctly identified in 52.9% of the samples. Comparisons based on BC bottle type, showed that the BACTEC™ Lytic/10 Anaerobic/F culture vials performed the best. Conclusion: Our study provides a novel and effective sample preparation method for MALDI-TOF MS direct identification of pathogens from positive BC vials, with a lower cost ($1.5 vs. $ 7) albeit a slightly more laborious extracting process (an extra 15 min) compared with Sepsityper™ kit.


Etiology of Papilledema in Patients in the Eye Clinic Setting.
The study of health conditions associated with papilledema will augment the clinical judgment of eye care professionals treating patients with optic disc edema in determining the urgency of additional evaluation and counseling patients accordingly. To determine the incidence, demographic characteristics, and etiologies of papilledema based on a unique records-linkage research platform; and to describe the demographic and clinical differences between patients with idiopathic intracranial hypertension (IIH) and other causes of papilledema. Retrospective population-based cross-sectional study of patients treated for papilledema at outpatient eye clinics in Olmsted County, Minnesota, using the Rochester Epidemiology Project. Data were collected from January 1990 to December 2014 and analyzed from September 2018 to April 2019. Etiologies of papilledema, body mass index, incidence of headache, or localizing neurologic signs. Eighty-six patients were diagnosed with papilledema during the 24-year period, providing an age- and sex-adjusted incidence of 2.5 individuals per 100 000 per year; 68 patients (79%) were women, 73 (85%) were white patients, and the median (range) age was 27.7 (6.2-64.2) years. Nineteen patients (22%) presented with a previously diagnosed attributable cause (eg, trauma or intracranial tumor). Among patients presenting with papilledema without a previously diagnosed attributable cause, 58 patients (87%) had IIH, and 9 patients (13%) were found to have a secondary cause of raised intracranial pressure, such as intracranial tumor, cerebral venous sinus thrombosis, or granulomatous meningitis. Patients with IIH had a higher median (range) body mass index (37.5 [20.4-55.7] vs 27.4 [16.6-40.1]; P = .003) and headache prevalence (54 of 58 patients [93%] vs 6 of 9 patients [67%]; P = .004) than patients with other causes of papilledema. Of 9 patients with papilledema but no IIH, 2 (22%) had localizing neurologic signs, such as gait abnormalities, hearing loss, focal weakness or numbness, visual field defects, or aphasia. Among 42 patients with demographic characteristics typically associated with IIH (female sex, with obesity, aged 15 to 45 years, and absent localizing neurologic signs or symptoms), 40 (95%) had papilledema that was associated with IIH. Conversely, among the 19 patients without these demographic characteristics, 7 (37%) had an alternative cause. In this study, most patients who presented to the eye clinic with papilledema without a previously known cause were found to have IIH. These patients were more likely to present with headaches and had statistically higher body mass index. Clinicians should take these findings into account when determining the pretest probability of a patient having IIH or an alternative cause of papilledema.