Prospective study of systemic lupus erythematosus pregnancies.
Different study designs have yielded different results on the effect of pregnancy on systemic lupus erythematosus (SLE) disease activity. Using the patient as her own control, and using nonpregnant SLE patients as controls, we have found flares to be more common in pregnancy. In SLE pregnancies followed prospectively at one center, we have found that preterm birth is the most frequent adverse event. Pregnancy loss occurred in 14%. Active SLE contributes to both preterm birth and to pregnancy loss. In addition, even in a first pregnancy, the presence of the lupus anticoagulant is associated with an increased risk of pregnancy loss.


Engaging civil society through deliberative dialogue to create the first Mental Health Strategy for Canada: Changing Directions, Changing Lives.
Citizen engagement through deliberative dialogue is increasingly being used to address 'wicked problems' in policy-making, such as the development of national mental health policy. In 2012, the Mental Health Commission of Canada (MHCC), a national organization funded by and operating at arm's length from the federal government, released the first Mental Health Strategy for Canada: Changing Directions, Changing Lives (Mental Health Commission of Canada, 2012). Despite much-needed reform, Canada, unlike most other industrialized countries, had never previously developed a national Mental Health Strategy (the Strategy). This was due to a mix of policy factors, including a federalist system of government where primary responsibility for healthcare resides with provincial and territorial governments and a highly diverse set of stakeholder groups with diverging core ideas for mental health reform that were rooted in deeply held value differences. In this case study, we review the essential role that engagement of civil society played in the creation of the Strategy, beginning with the efforts to create a national body to shine the light on the need for mental health reform in Canada, followed by the development of a framework of specific goals based on core principles to guide the development of the Strategy, and ultimately, the creation of the Strategy itself. We discuss the various approaches to civil society engagement in each step of this process and focus in particular on how deliberative approaches helped build trust and common ground amongst stakeholders around complex, and often contentious, issues. The nature and outcomes of the deliberative processes including the key tensions between different stakeholder perspectives and values are described. We close by highlighting the lessons learned in a process that culminated with a Strategy that received strong endorsement from stakeholders across Canada. Mental Health Commission of Canada (2012). Changing Directions Changing Lives, The Mental Health Strategy for Canada. Calgary, AB: MHCC.


Parenteral nutrition and urban legends.
To assess the recent literature regarding parenteral nutrition to identify publications that have purported to support various beliefs about the utility of parenteral nutrition, and then to critically evaluate the data presented in those (as well as prior) publications. Artificial nutrition improves nutritional markers but not clinical outcomes, suggesting that malnutrition is not causatively associated with a poor outcome. There are no convincing data that parenteral nutrition is beneficial in severely malnourished surgical patients. Glutamine supplementation of parenteral nutrition solutions may reduce the infectious complication rate, but it is unknown if glutamine-supplemented parenteral nutrition is better than no parenteral nutrition. Most, but not all, systematic reviews have demonstrated that enteral nutrition produces fewer problems than parenteral nutrition; no data suggest that either modality is better than doing no artificial nutrition. Randomized trials have not uniformly been able to demonstrate that parenteral nutrition is efficacious in acute pancreatitis. There is some, but not convincing, data that a regimen of glutamine, growth hormone, and a specialized diet will reduce the need for parenteral nutrition in patients with short bowel syndrome. It is important for clinicians to be able to critically evaluate the medical literature.


Correction: Prevalence of mental health problems among children with long COVID: A systematic review and meta-analysis.
[This corrects the article DOI: 10.1371/journal.pone.0282538.].


Practice patterns and clinical outcomes after hybrid coronary revascularization in the United States: an analysis from the society of thoracic surgeons adult cardiac database.
Hybrid coronary revascularization (HCR) involves a combination of surgical and percutaneous techniques, which in selected patients may present an alternative to conventional coronary artery bypass grafting (CABG). Patients were included who underwent HCR (staged/concurrent) or isolated CABG in the Society of Thoracic Surgeons Adult Cardiac Surgery Database (July 2011 to March 2013). HCR represented 0.48% (n=950; staged=809, concurrent=141) of the total CABG volume (n=198,622) during the study period, and was performed in one-third of participating centers (n=361). Patients who underwent HCR had higher cardiovascular risk profiles in comparison with patients undergoing CABG. In comparison with CABG, median sternotomy (98.5% for CABG, 61.1% for staged HCR, and 52.5% for concurrent HCR), direct vision harvesting (98.9%, 66.0%, and 68.1%) and cardiopulmonary bypass (83.4%, 45%, and 36.9%) were less frequently used for staged and concurrent HCR, whereas robotic assistance (0.7%, 33.0%, and 30.5%) was more common. After adjustment, no differences were observed for the composite of in-hospital mortality and major morbidity (odds ratio, 0.93; 95% confidence interval, 0.75-1.16; P=0.53 for staged HCR, and odds ratio, 0.94; 95% confidence interval, 0.56-1.56; P=0.80 for concurrent HCR in comparison with CABG). There was no statistically significant association between operative mortality and either treatment group (odds ratio, 0.74; 95% confidence interval, 0.42-1.30; P=0.29 for staged HCR, and odds ratio, 2.26; 95% confidence interval, 0.99-5.17; P=0.053 for concurrent HCR in comparison with CABG). HCR, either as a staged or concurrent procedure, is performed in one-third of US hospitals and is reserved for a highly selected patient population. Although HCR may appear to be an equally safe alternative for CABG surgery, further randomized study is warranted.


The cooperation link: Power and context moderate verbal mimicry.
Drawing on theories of mimicry as a schema-driven process, we tested whether the degree of verbal mimicry is dependent on the congruence between interactants' power dynamic (symmetric versus asymmetric), task type (cooperative versus competitive), and interaction context (negotiation versus social). Experiment 1 found higher verbal mimicry among dyads who successfully completed a cooperative problem-solving task compared with those who did not, but only under conditions of symmetric, not asymmetric, power. Experiment 2 had dyads complete either a cooperative or a competitive negotiation task, under conditions of symmetric versus asymmetric power. Verbal mimicry was associated with improved negotiation outcomes under conditions of cooperation and symmetry, and competition and asymmetry. Experiment 3 completes this picture by separating cooperative-competitive orientation from the interaction context. Consistent with Experiment 2, verbal mimicry was associated with task success during a negotiation context with asymmetric power, and during a social interaction context with symmetric power. Our results point to the contextual link between verbal mimicry and task outcome. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Multilocus Sequence Typing Reveals Extensive Genetic Diversity of the Emerging Fungal Pathogen Scedosporium aurantiacum.
Scedosporium spp. are the second most prevalent filamentous fungi after Aspergillus spp. recovered from cystic fibrosis (CF) patients in various regions of the world. Although invasive infection is uncommon prior to lung transplantation, fungal colonization may be a risk factor for invasive disease with attendant high mortality post-transplantation. Abundant in the environment, Scedosporium aurantiacum has emerged as an important fungal pathogen in a range of clinical settings. To investigate the population genetic structure of S. aurantiacum, a MultiLocus Sequence Typing (MLST) scheme was developed, screening 24 genetic loci for polymorphisms on a tester strain set. The six most polymorphic loci were selected to form the S. aurantiacum MLST scheme: actin (ACT), calmodulin (CAL), elongation factor-1α (EF1α), RNA polymerase subunit II (RPB2), manganese superoxide dismutase (SOD2), and β-tubulin (TUB). Among 188 global clinical, veterinary, and environmental strains, 5 to 18 variable sites per locus were revealed, resulting in 8 to 23 alleles per locus. MLST analysis observed a markedly high genetic diversity, reflected by 159 unique sequence types. Network analysis revealed a separation between Australian and non-Australian strains. Phylogenetic analysis showed two major clusters, indicating correlation with geographic origin. Linkage disequilibrium analysis revealed evidence of recombination. There was no clustering according to the source of the strains: clinical, veterinary, or environmental. The high diversity, especially amongst the Australian strains, suggests that S. aurantiacum may have originated within the Australian continent and was subsequently dispersed to other regions, as shown by the close phylogenetic relationships between some of the Australian sequence types and those found in other parts of the world. The MLST data are accessible at http://mlst.mycologylab.org. This is a joined publication of the ISHAM/ECMM working groups on "Scedosporium/Pseudallescheria Infections" and "Fungal Respiratory Infections in Cystic Fibrosis".


Cone-beam computed tomography produces images of numerically comparable diagnostic quality for bone and inferior quality for soft tissues compared with fan-beam computed tomography in cadaveric equine metacarpophalangeal joints.
Cone-beam computed tomography (CBCT) is an emerging modality for imaging of the equine patient. The objective of this prospective, descriptive, exploratory study was to assess visualization tasks using CBCT compared with conventional fan-beam CT (FBCT) for imaging of the metacarpophalangeal joint in equine cadavers. Satisfaction scores were numerically excellent with both CBCT and FBCT for bone evaluation, and FBCT was numerically superior for soft tissue evaluation. Preference tests indicated FBCT was numerically superior for soft tissue evaluation, while preference test scoring for bone was observer-dependent. Findings from this study can be used as background for future studies evaluating CBCT image quality in live horses.


Telomere length alterations unique to invasive lobular carcinoma.
Telomeres are nucleoprotein complexes located at the extreme ends of eukaryotic chromosomes and protect chromosomal ends from degradation and recombination. Dysfunctional telomeres contribute to genomic instability, promote tumorigenesis, and, in breast cancer, have been associated with increased cancer risk and poor prognosis. Short telomere lengths have been previously associated with triple-negative and human epidermal growth factor receptor (Her2)--positive ductal carcinomas. However, these investigations have not specifically assessed invasive lobular carcinomas (ILCs), which accounts for 5% to 15% of all invasive breast cancers. Here, we evaluate telomere lengths within 48 primary ILCs with complete characterization of estrogen receptor (ER), progesterone receptor (PR), and Her2 status, including 32 luminal/Her2- (ER+/PR+/Her2-), 8 luminal/Her2+ (ER+/PR+/Her2+), 3 Her2+ (ER-/PR-/Her2+), and 5 triple-negative (ER-/PR-/Her2-) carcinomas. A telomere-specific fluorescence in situ hybridization assay, which provides single-cell telomere length resolution, was used to evaluate telomere lengths and compare with standard clinicopathological markers. In contrast to breast ductal carcinoma, in which more than 85% of cases display abnormally short telomeres, approximately half (52%) of the ILCs displayed either normal or long telomeres. Short telomere length was associated with older patient age. Interestingly, 3 cases (6%) displayed a unique telomere pattern consisting of 1 or 2 bright telomere spots among the normal telomere signals within each individual cancer cell, a phenotype that has not been previously described. Additional studies are needed to further evaluate the significance of the unique bright telomere spot phenotype and the potential utility of telomere length as a prognostic marker in ILC.


[Comparative studies on dose adjustment of intraoperative lidocaine therapy in heart failure patients].
From 10 patients with myocardial insufficiency arterial blood samples were taken, in order to study lidocaine plasma concentrations following reduced iv. bolus administration (0.5 mg/kg body weight) and subsequent infusion (2 mg/min). Drug concentrations were monitored by means of gas chromatography. The results obtained from the reduced loading dose of lidocaine were nearly identical to those from patients without myocardial insufficiency and an iv. bolus injection of 1 mg lidocaine/kg body weight. The reduced hepatic metabolism of lidocaine caused by manifest myocardial insufficiency requires a significantly reduced loading dose not exceeding the therapeutic range, even in intraoperative short-term use.


From clinical practice to guidelines: how to recognize rhinosinusitis in children.
Rhinosinusitis is a common childhood respiratory infection. Children have approximately six to eight viral infections of the upper respiratory tract each year, 5-13% of which may be complicated by a secondary bacterial infection of the paranasal sinuses. The diagnosis of acute bacterial rhinosinusitis in children is established by the persistence of purulent nasal or post-nasal draining lasting at least 10 days, especially if accompanied by supporting symptoms and signs, at which point antibiotic treatment has to be recommended. Appropriate antibacterial therapy should also be recommended if the draining has been present for less time, but is concomitantly associated with significant fever and localized signs of sinus inflammation in a child who appears ill. Imaging studies are not necessary to confirm the diagnosis of clinical rhinosinusitis for the purposes of treatment, but should be reserved for cases in which the diagnosis is in doubt or a complication is suspected, and for patients with recurrent or chronic rhinosinusitis. Under these circumstances, computed tomography is the preferred evaluation. Together with their clinical judgment, these suggestions may be useful for pediatricians in diagnosing this common condition.


Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop.
The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.


The effect of recombinant human erythropoietin on the efficacy of autologous blood donation in patients with low hematocrits: a multicenter, randomized, double-blind, controlled trial.
This randomized controlled study was undertaken to determine the effect of recombinant human erythropoietin (rHuEPO) on erythropoiesis, autologous blood collection, and allogeneic transfusion risk in elective surgery patients with low baseline hematocrits. Patients (n = 204) with low baseline hematocrits ( < or = 39%), scheduled for orthopedic surgery within 25 to 35 days, were seen every 3 to 4 days for 21 days. At each visit, 450 mL of blood was collected if the hematocrit was > or = 33 percent, and rHuEPO (600 U/kg) or placebo was administered intravenously. One hundred seventy-three patients were evaluable. The number of autologous units collected from the rHuEPO and control groups, respectively, was 4.5 +/- 1.0 and 3.0 +/- 1.1 (p < 0.001), and marrow production of red cells increased by 668 +/- 222 and 353 +/- 155 mL over and above baseline production (p < 0.05). Allogeneic blood transfusion was required by 31 percent of control and 20 percent of rHuEPO patients (p = 0.09). Excluding 8 patients who received > 6 units, 29 percent of control and 14 percent of rHuEPO patients required allogeneic blood (p = 0.015). Logistic regression modeling determined that the risk of allogeneic transfusion was reduced by rHuEPO (p = 0.025). The use of rHuEPO stimulates erythropoiesis, permits the storage of more autologous blood, and reduces allogeneic transfusion risk in patients with low hematocrits who are undergoing elective orthopedic surgery. Additional studies are necessary to determine the optimal schedules of rHuEPO administration and autologous blood collection as well as the cost-effectiveness of this strategy.


The physical activity paradox in relation to work ability and health-related productivity loss.
The physical activity paradox suggests that occupational physical activity (OPA), unlike leisure-time physical activity (LTPA), may detrimentally impact health. We explored the relationships of OPA and LTPA with work ability (WA) and health-related productivity loss (HRPL). This study included 5,501 workers in Korea who were recruited in 2021 through a web-based cross-sectional questionnaire. The questionnaire was utilized to quantify OPA and LTPA in metabolic equivalents, while WA and HRPL were also measured. Non-parametric regression, using a generalized additive model (GAM), was employed to visualize the relationships of LTPA and OPA with WA and HRPL. Mean differences in WA and HRPL, in relation to OPA and LTPA, were examined using linear regression models. These models were adjusted for covariates including sex, age, body mass index, education level, alcohol consumption, smoking history, insomnia, occupation, hours worked, and income. The GAM and linear regression analyses revealed that higher LTPA corresponded with higher WA and lower HRPL. In contrast, as OPA increased, WA decreased and HRPL increased. However, within the group with high OPA, HRPL was not significantly lower in the high-LTPA subgroup relative to the low-LTPA subgroup (mean difference 1.92%; p = 0.343). This pattern was especially pronounced among workers aged 60 years and older, with an increase in HRPL observed with increasing LTPA among the respondents with high OPA. High LTPA levels were associated with elevated WA and diminished HRPL. In contrast, higher levels of OPA were associated with lower WA and higher HRPL.


Transcriptome analysis of genes potentially associated with white and black plumage formation in Chinese indigenous ducks (Anas platyrhynchos).
1. Plumage colour is an important recognisable characteristic of duck (Anas platyrhynchos), but the colouration mechanisms remain largely unknown. To elucidate the molecular mechanisms underlying the formation of black and white plumage, the following study applied RNA sequencing (RNA-Seq) to catalogue the global gene expression profiles in the duck feather bulbs of black and white colours.2. Black feather bulbs were collected from Putian Black ducks (B-PTB) and black Longsheng Jade-green ducks (B-LS), while white feather bulbs were collected from Putian White ducks (W-PTW), Putian Black ducks (W-PTB) and Longsheng Jade-green ducks (W-LS). Sixteen cDNA libraries were constructed and sequenced for transcriptional analysis. Three comparison groups were employed to analyse differentially expressed genes (DEGs), including W-PTB versus B-PTB, W-PTW versus B-PTB and W-LS versus B-LS.3. The results showed 180 DEGs between W-PTB and B-PTB, 303 DEGs between W-PTW and B-PTB, and 108 DEGs between W-LS and B-LS. Further analysis showed that 18 DEGs were directly involved in the pigmentation process and melanogenesis signalling pathway. Additionally, the distribution of DEGs varied amongst groups whereby ASIP appeared only in the W-LS versus B-LS group, GNAI1 and ZEB2 appeared only in the W-PTW versus B-PTB group, and KITLG, EDN3 and FZD4 appeared only in W-PTB versus B-PTB.4. The findings suggested that the mechanism of feather albinism may differ between duck breeds. This study provided new information for discovering genes that are important for feather pigmentation and helps elucidate molecular mechanisms involved in black and white plumage in ducks.


Root-secreted malic acid recruits beneficial soil bacteria.
Beneficial soil bacteria confer immunity against a wide range of foliar diseases by activating plant defenses, thereby reducing a plant's susceptibility to pathogen attack. Although bacterial signals have been identified that activate these plant defenses, plant metabolites that elicit rhizobacterial responses have not been demonstrated. Here, we provide biochemical evidence that the tricarboxylic acid cycle intermediate L-malic acid (MA) secreted from roots of Arabidopsis (Arabidopsis thaliana) selectively signals and recruits the beneficial rhizobacterium Bacillus subtilis FB17 in a dose-dependent manner. Root secretions of L-MA are induced by the foliar pathogen Pseudomonas syringae pv tomato (Pst DC3000) and elevated levels of L-MA promote binding and biofilm formation of FB17 on Arabidopsis roots. The demonstration that roots selectively secrete L-MA and effectively signal beneficial rhizobacteria establishes a regulatory role of root metabolites in recruitment of beneficial microbes, as well as underscores the breadth and sophistication of plant-microbial interactions.


Diagnosis of thin-cap fibroatheromas by a self-contained intravascular magnetic resonance imaging probe in ex vivo human aortas and in situ coronary arteries.
We sought to correlate findings obtained from a self-contained magnetic resonance imaging (MRI) probe with plaque morphology of ex vivo human aortas and coronary arteries. Early detection of thin-cap fibroatheromas (TCFAs) may allow for early preventive treatment of acute coronary syndromes. We developed an intravascular MRI catheter capable of imaging the arterial wall without external magnets or coils by differentiating lipid-rich and fibrotic-rich areas of the atherosclerotic plaque on the basis of differential water diffusion. Aortic samples (n = 16) and coronary arteries were obtained within 12 h of death. Coronary specimens were intermediate in angiographic severity (30% to 60% luminal narrowing, n = 18). Blinded histologic and immunohistochemical analyses of the tissues were performed and correlated to MRI findings. The 16 aortic lesions included four ulcerated plaques, two TCFAs, two thick-cap fibrous atheromas, two intimal xanthomas, and six adaptive intimal thickenings. The MRI scan correctly correlated with the histologic diagnosis in 15 (94%) of 16 lesions. The 18 coronary lesions included one plaque rupture, three TFCAs, seven thick-cap fibrous atheromas, four fibrocalcific plaques, two intimal xanthomas, and one adaptive intimal thickening. The MRI scan correlated with the histologic diagnosis in 16 of 18 lesions (sensitivity 100%, specificity 89%). The self-contained intravascular MRI catheter successfully identified TCFA and may prove to be an important diagnostic approach to determining the presence of lesions with increased risk of causing death or myocardial infarction.


Soft Ionic Electroactive Polymer Actuators with Tunable Non-Linear Angular Deformation.
The most rational approach to fabricate soft robotics is the implementation of soft actuators. Conventional soft electromechanical actuators exhibit linear or circular deformation, based on their design. This study presents the use of conjugated polymers, Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) to locally vary ion permeability of the ionic electroactive polymer actuators and manipulate ion motion through means of structural design to realize intrinsic angular deformation. Such angular deformations are closer to biomimetic systems and have potential applications in bio-robotics. Electrochemical studies reveal that the mechanism of actuation is mainly associated with the charging of electric double layer (EDL) capacitors by ion accumulation and the PEDOT:PSS layer's expansion by ion interchange and penetration. Dependence of actuator deformation on structural design is studied experimentally and conclusions are verified by analytical and finite element method modeling. The results suggest that the ion-material interactions are considerably dominated by the design of the drop-cast PEDOT:PSS on Nafion.


Adjuvant CMF in breast cancer: comparative 5-year results of 12 versus 6 cycles.
We report the 5-yr results of a prospective randomized study comparing 12 versus 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) with the aim to evaluate the possibility of reducing the duration of adjuvant treatment without compromising the therapeutic effect of the multimodal approach. At 5-yr from mastectomy, both relapse-free survival (CMF 12: 59%; CMF 6: 65.6%) and total survival (CMF 12: 72.7%; CMF 6: 76.9%) were not significantly different in the two treatment groups. Within the two series, no difference was detected between pre- and postmenopausal patients (CMF 12: 59.3% versus 57.6%; CMF 6: 66.5% versus 63.1%), while findings were inversely related to the number of involved axillary nodes. The analysis of relapse-free survival confirmed that in both menopausal groups, relapse-free survival was not significantly affected by estrogen receptor status. Acute toxic manifestations were moderate and reversible. In particular, no drug-induced leukemia nor increased incidence of solid tumors other than breast cancer were documented in this series. Present results after 12 CMF cycles are almost identical to those of our first CMF adjuvant study. Current findings are sufficiently mature to indicate that the maximum tumor cytoreduction with CMF occurs within a relatively short period of time. To improve the results achieved with a single multidrug regimen, more intensive forms of treatment, i.e., utilizing non-cross-resistant combinations, warrant careful evaluation.


Motherhood through medically assisted reproduction - characteristics and motivations of Swedish single mothers by choice.
Characteristics and motivations of single mothers by choice were assessed in this pilot study, after new legislation in 2016 allowing access to medically assisted reproduction (MAR). Single women at a university clinic in Sweden were sent a postal questionnaire to their home address (n = 86) and 54 (62.8%) women filled it out and returned it. The women had a mean age of 35.1 years and were well-educated. Most of them worked full-time, were permanently employed, and had a stable income. They had previously had long-term relationships, although these had not been right for having children. More women (61%) could consider embryo donation rather than adoption (50%) (p < 0.05). The motivations most commonly cited for choosing motherhood by MAR was that because of their age, having a child was more important than waiting for the right partner. Nevertheless, they still had hope to find a partner in the future. In conclusion, Swedish single women accepted for MAR are no different from other single mothers by choice: they are financially and socially stable, and choose motherhood by MAR due to their advanced age and not wanting to wait too long in order to meet the right partner.


The 1985 national immunisation survey: hepatitis A.
In April 1985 a national immunisation survey was carried out, during which sera were collected from approximately 3000 randomly selected children throughout New Zealand. The sample comprised approximately equal numbers of new school entrants (mean age 5 years), standard 3 pupils (mean age 10 years) and form 4 students (mean age 15 years). This collection of sera was tested for antibody to hepatitis A virus, a marker of past infection with this virus, by means of a sensitive ELISA test. Prevalence of infection was found to be less than 1% in the 5 year olds, about 3% in the 10 year olds, and about 9% in the 15 year olds. Amongst the 10 and 15 year olds, but not the 5 year olds, Maori children were approximately three times more likely to have been infected than European children. Children resident in the eastern part of the North Island had a higher risk of infection than other children, even after controlling for ethnic distribution.


Indoor fungi and their ciliostatic metabolites.
According to epidemiological studies, it is possible that some secondary metabolites of indoor airborne fungi could be responsible for health troubles which occupants suffer from. In our previous experiments, a model with tracheal rings of 1-day-old chicks in vitro was shown to be a very suitable method to study the ciliostatic chloroform-extractable endo- and/or exometabolites of filamentous fungi. In this study we isolated the filamentous fungi from walls of "mouldy" dwellings and schools (cultivation on dichloran 18% glycerol agar at 25 and 37 degrees C for 10 d) in Slovakia. We studied the ciliostatic effect of the chloroform-extractable endo- and exometabolites of 96 representative isolates (stationary cultivation on the liquid medium with 2% of yeast extract and 10% of sucrose at 25 degrees C for 10 days) on the cilia movement in tracheal organ cultures of 1-day-old chickens in vitro after 24, 48 and 72 hrs (incubation in the minimal essential medium according to Eagle with Earl s salts and 20 microg of extract of metabolites dissolved in dimethylsulfoxide per 1 mL). Strains of Penicillium Link: Fr. sp., Aspergillus versicolor (Vuill.) Tiraboschi, A. flavus Link, Cladosporium sphaerospermum Penzig and C. cladosporioides (Fres.) de Vries were isolated most frequently. Two A. flavus isolates were able to produce aflatoxins B1, B2, G1, G2 in vitro after cultivation on the liquid medium with 20% sucrose and 2% yeast extract. This is the first isolation of aflatoxigenic A. flavus strains from dwellings in Slovakia. All frequently isolated strains produced secondary metabolites with the strongest ciliostatic activity -- their exo- and endometabolites stopped tracheal ciliary movement in chicks till 24 h. There are some toxic fungal metabolites in the indoor air not only with the ability to destroy ciliary movement in the upper airways in vitro but, probably, during long-lasting exposure to cause general intoxication of macroorganism via lung tissue.


Comparing the Incidence and Clinical Data for Simultaneous Bilateral Versus Unilateral Total Hip Arthroplasty in New York State Between 1990 and 2010.
A New York State database reported information on all total hip arthroplasty cases between 1990 and 2010 comparing unilateral (242,588 cases) to simultaneous bilateral (4538 cases) procedures. Our data showed that the population incidence of this surgery increased 120.2% over twenty years, yet the proportionate number of simultaneous cases has decreased. Simultaneous procedures were found to occur more commonly in younger patients with private insurance. In addition, bilateral procedures showed an increase in PE, DVT, length of stay, and discharge to rehab facilities; whereas mortality and blood transfusions compared to unilateral procedures showed no difference.


Combining chemo-, hormonal and targeted therapies to treat breast cancer (Review).
Breast cancer ranks as the second most common cause of cancer death among women in the United States. Anticancer agents are an important component of breast cancer therapy. Drugs frequently used to treat breast cancer include methotrexate, 5-fluorouracil (5-FU), cyclophosphamide, anthracyclines, taxanes, trastuzumab, tamoxifen and aromatase inhibitors. These agents inhibit breast cancer progression by a variety of different mechanisms. Mutations may occur in cancer cells, which result in the elevated expression or constitutive activation of various growth factor receptors. The Raf/MEK/ERK and PI3K/Akt pathways are often activated by mutations in these growth factor receptors. These pathways are regulated by upstream Ras, which is mutated in 20-30% of human cancers. Downstream B-Raf and PI3K are also activated by mutation. Many of the events elicited by the Raf/MEK/ERK and PI3K/Akt pathways have direct effects on survival and the proliferative pathways. Aberrant regulation of the Raf/MEK/ERK and PI3K/Akt pathways can contribute to uncontrolled cell growth and lead to malignant transformation. Effective targeting of these pathways may result in the suppression of cell growth and the death of malignant cells. This review focuses on the targeting of the Raf/MEK/ERK and PI3K/Akt pathways with small molecule inhibitors, as well as on the effects of conventional chemo- and hormonal therapies in the treatment of breast cancer.


Determinants of fine manual dexterity in adolescents and young adults with Down's syndrome.
To date, numbers of studies have indicated the important role of fine manual dexterity in typical and special populations. However, the relevant studies in Down's syndrome (DS) population is still limited. The purpose of this study was to investigate the determinants of manual dexterity in adolescents and young adults with DS. Thirty participants with DS (22 males, 8 females, aged 13-31) were screened by anthropometric variables (i.e. sex, chronological age, verbal intelligence, body mass index), levels of physical activity, and sleep disorders, and were administered the Purdue Pegboard Test and the Choice Reaction Time Test. Measures of correlation, t-test and multiple regression model were used for data analysis. It was indicated that sex and sleep-related disorders during the day explained 37.2% of the variance in the performance of the Purdue Pegboard Test. The additional of 9.7% can be explained the variance by adding reaction time test performance. Verbal intelligence had the negatively relation with the performance of non-Dominant Hand and Bimanual subtests of the Purdue Pegboard Test. This study suggested that sex, sleep disorder, and neuromotor function may be the important determinants of fine manual dexterity performance in adolescents and young adults with DS. In addition, the level of intelligence might also exert the effect on fine motor development in this population. In order to design effective interventions and optimize manual performance in individuals with DS, these possible determinants should be considered. Future research should be replicated with large sample size, different age groups, and validated measures of finger size, physical activity and sleep behaviors.


Differential efficacy of gels derived from small intestinal submucosa as an injectable biomaterial for myocardial infarct repair.
Injectable biomaterials have been recently investigated as a therapeutic approach for cardiac repair. Porcine-derived small intestinal submucosa (SIS) material is currently used in the clinic to promote accelerated wound healing for a variety of disorders. In this study, we hypothesized that gels derived from SIS extracellular matrix would be advantageous as an injectable material for cardiac repair. We evaluated 2 forms of SIS gel, types B (SIS-B) and C (SIS-C), for their ability to provide a therapeutic effect when injected directly into ischemic myocardium using a murine model of an acute myocardial infarction. Echocardiography analysis at both 2 and 6 weeks after infarction demonstrated preservation of end-systolic left ventricular geometry and improvement of cardiac contractility in the hearts injected with SIS-B when compared with control hearts injected with saline. However, the SIS-C gel provided no functional efficacy in comparison with control. Histological analysis revealed that SIS-B reduced infarct size and induced angiogenesis relative to control, whereas injection of SIS-C had minimal effect on these histological parameters. Characterization of both gels revealed differential growth factor content with SIS-B exhibiting higher levels of basic fibroblast growth factor than SIS-C, which may explain, at least in part, the differential histological and functional results. This study suggests that SIS gel offers therapeutic potential as an injectable material for the repair of ischemic myocardium. Further understanding of SIS gel characteristics, such as biological and physical properties, that are critical determinants of efficacy would be important for optimization of this biomaterial for cardiac repair.


β-catenin contributes to lung tumor development induced by EGFR mutations.
The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of EGFR-mutated lung cancers. β-Catenin was upregulated and activated in EGFR-mutated cells. Mutant EGFR preferentially bound to and tyrosine phosphorylated β-catenin, leading to an increase in β-catenin-mediated transactivation, particularly in cells harboring the gefitinib/erlotinib-resistant gatekeeper EGFR-T790M mutation. Pharmacologic inhibition of β-catenin suppressed EGFR-L858R-T790M mutated lung tumor growth, and genetic deletion of the β-catenin gene dramatically reduced lung tumor formation in EGFR-L858R-T790M transgenic mice. These data suggest that β-catenin plays an essential role in lung tumorigenesis and that targeting the β-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR TKIs.


Historical profile of gender in Turkish veterinary education.
Women in Turkey were first given the opportunity to attend schools of higher education in 1914. Following the establishment of the Turkish Republic in 1923, a number of social, judicial, and economic reforms took place that enabled women to participate actively in both the public and private sectors, and, as a consequence, the number of women students in higher education increased rapidly. The first woman graduated from the veterinary school in Ankara in 1935, becoming the first female veterinarian in the country. Since that time, the number of female veterinary graduates in Turkey has steadily increased.


Impact of the donor polymer on recombination via triplet excitons in a fullerene-free organic solar cell.
The greater chemical tunability of non-fullerene acceptors enables fine-tuning of the donor-acceptor energy level offsets, a promising strategy towards increasing the open-circuit voltage in organic solar cells. Unfortunately, this approach could open an additional recombination channel for the charge-transfer (CT) state via a lower-lying donor or acceptor triplet level. In this work we investigate such electron and hole back-transfer mechanisms in fullerene-free solar cells incorporating the novel molecular acceptor 2,4-diCN-Ph-DTTzTz. The transition to the low-driving force regime is studied by comparing blends with well-established donor polymers P3HT and MDMO-PPV, which allows for variation of the energetic offsets at the donor-acceptor interface. Combining various optical spectroscopic techniques, the CT process and subsequent triplet formation are systematically investigated. Although both back-transfer mechanisms are found to be energetically feasible in both blends, markedly different triplet-mediated recombination processes are observed for the two systems. The kinetic suppression of electron back-transfer in the blend with P3HT suggests that energy losses due to triplet formation on the polymer can be avoided, regardless of favorable energetic alignment.


Roles assessment in families of children with chronic renal failure on peritoneal dialysis.
Families with a child on chronic peritoneal dialysis have to assume a significant burden of care, intensifying the demands and the reorganization of roles in the families of children. The purpose of this study is to describe the implications of role changes in families of children with chronic renal disease on peritoneal dialysis. This is a case study of four families of children with chronic renal disease on peritoneal dialysis. Fourteen family members participate in the study. After the child's chronic kidney failure and the start of treatment, each relative's ways, acts and functions are changed, maintained or adapted to the new family dynamics, imposed by the child's treatment conditions. Appropriate role assessment provides the nurse and the families of children with chronic renal failure on peritoneal dialysis with insight regarding current and potential health problems and aids in identifying the needs of the families.


Vitamin B12 - a scoping review for Nordic Nutrition Recommendations 2023.
Vitamin B12 (cobalamin) is essential for normal metabolic function, and even moderate deficiency of this vitamin has negative health effects. Vitamin B12 is found in animal foods, and as vegetarian diets are increasingly popular in Western countries, one might expect a higher prevalence of vitamin B12 deficiency in the Nordic population. Setting recommendations for vitamin B12 intake has proven to be difficult, as uptake of vitamin B12 varies substantially, the clinical deficiency symptoms are often diffuse, and there is no clear agreement on the decision limits for vitamin B12 deficiency. Vitamin B12 deficiency is reported to be particularly common among pregnant women and infants, despite the fact that less than 1% of Norwegian pregnant women have a cobalamin intake below the Nordic Nutrition Recommendations 2012-recommended level of 2.0 µg/day. In addition, the assumption that breast milk contains sufficient vitamin B12 for optimal health and neurodevelopment during the first 6 months of life does not comply with the high prevalence of insufficient vitamin B12 status in this age group. Recommended intakes of vitamin B12 vary among age groups and must be based on markers of cobalamin status, indicating an optimal intracellular biochemical status, and not merely absence of clinical signs of vitamin B12 deficiency.


Communication: Modeling of concentration dependent water diffusivity in ionic solutions: Role of intermolecular charge transfer.
The translational diffusivity of water in solutions of alkali halide salts depends on the identity of ions, exhibiting dramatically different behavior even in solutions of similar salts of NaCl and KCl. The water diffusion coefficient decreases as the salt concentration increases in NaCl. Yet, in KCl solution, it slightly increases and remains above bulk value as salt concentration increases. Previous classical molecular dynamics simulations have failed to describe this important behavior even when polarizable models were used. Here, we show that inclusion of dynamical charge transfer among water molecules produces results in a quantitative agreement with experiments. Our results indicate that the concentration-dependent diffusivity reflects the importance of many-body effects among the water molecules in aqueous ionic solutions. Comparison with quantum mechanical calculations shows that a heterogeneous and extended distribution of charges on water molecules around the ions due to ion-water and also water-water charge transfer plays a very important role in controlling water diffusivity. Explicit inclusion of the charge transfer allows us to model accurately the difference in the concentration-dependent water diffusivity between Na(+) and K(+) ions in simulations, and it is likely to impact modeling of a wide range of systems for medical and technological applications.


Optimal stent length and distal positioning of frozen elephant trunks deployed from the aortic zone 0 for type A acute aortic dissection.
To investigate the optimal stent length and distal positioning of frozen elephant trunks (FETs) in patients with type A acute aortic dissection (TAAD). Between October 2014 and April 2021, 191 patients (FET-150 group: 37 patients; stent length, 150 mm; 66.3 ± 12.6 years and FET-non-150 group: 154 patients; 60, 90, or 120 mm; 64.1 ± 12.5 years) underwent total arch repair with FETs for TAAD using the "zone 0 arch repair" strategy. In the FET-150 group, the proximal stent end was positioned at the innominate artery origin of the arch. In the FET-non-150 group, the distal stent end was to be positioned just proximal to the aortic valve level using transesophageal echocardiography. The proximal end of the non-stented FET part was sutured to an arch graft together with the aortic wall at 1 to 2 cm proximal to the innominate artery origin. Distal stent ends were positioned at the thoracic vertebrae (Th) 4-5, 6-7, 8-9, and 10 levels in 0 (0%), 12 (32.4%), 25 (67.6%), and 0 (0%) patients, respectively, in the FET-150 group, and in 6 (3.9%), 98 (63.6%), 49 (31.8%), and 1 (0.7%), respectively, in the FET-non-150 group. No between-group difference in postoperative mortality was noted. The incidence of postoperative residual distal malperfusion and new-onset spinal cord ischemia in the FET-150 versus FET-non-150 groups were 2.7% versus 6.5% (P = .62) and 0% versus 1.9% (P = 1.00), respectively. FET positioning with the distal stent end at around Th 8 can reduce residual distal malperfusion when a FET with a 150-mm stent is deployed from the aortic zone 0 in patients with TAAD undergoing total arch repair.


Excess burden of non-communicable disease years of life lost from heat in rural Burkina Faso: a time series analysis of the years 2000-2010.
Investigate the association of heat exposure on years of life lost (YLL) from non-communicable diseases (NCD) in Nouna, Burkina Faso, between 2000 and 2010. Daily time series regression analysis using distributed lag non-linear models, assuming a quasi-Poisson distribution of YLL. Nouna Health and Demographic Surveillance System, Kossi Province, Rural Burkina Faso. 18 367 NCD-YLL corresponding to 790 NCD deaths recorded in the Nouna Health and Demographic Surveillance Site register over 11 years. Excess mean daily NCD-YLL were generated from the relative risk of maximum daily temperature on NCD-YLL, including effects delayed up to 14 days. Daily average NCD-YLL were 4.6, 2.4 and 2.1 person-years for all ages, men and women, respectively. Moderate 4-day cumulative rise in maximum temperature from 36.4°C (50th percentile) to 41.4°C (90th percentile) resulted in 4.44 (95% CI 0.24 to 12.28) excess daily NCD-YLL for all ages, rising to 7.39 (95% CI 0.32 to 24.62) at extreme temperature (42.8°C; 99th percentile). The strongest health effects manifested on the day of heat exposure (lag 0), where 0.81 (95% CI 0.13 to 1.59) excess mean NCD-YLL occurred daily at 41.7°C compared with 36.4°C, diminishing in statistical significance after 4 days. At lag 0, daily excess mean NCD-YLL were higher for men, 0.58 (95% CI 0.11 to 1.15) compared with women, 0.15 (95% CI -0.25 to 9.63) at 41.7°C vs 36.4°C. Premature death from NCD was elevated significantly with moderate and extreme heat exposure. These findings have important implications for developing adaptation and mitigation strategies to reduce ambient heat exposure and preventive measures for limiting NCD in Africa.


Effects of GH and IGF1 on Basal and FSH-Modulated Porcine Sertoli Cells In-Vitro.
Several lines of evidence suggest that insulin-like growth factor 1 (IGF1) is involved in Sertoli cell (SC) proliferation and that its receptor (IGF1R) could mediate follicle-stimulating hormone (FSH) effects. To examine the role of the growth hormone (GH)-IGF1 axis on SC function, we evaluated the effects of GH and IGF1 on basal and FSH-modulated SC proliferation, as well as on anti-Müllerian hormone (AMH) and inhibin B expression and secretion in-vitro. SCs from neonatal pigs were incubated with (1) placebo, (2) 100 nM highly purified urofollitropin (hpFSH), (3) 100 nM recombinant GH (rGH), (4) 100 nM recombinant IGF1 (rIGF1), (5) 100 nM hpFSH plus 100 nM rGH, (6) 100 nM hpFSH plus 100 nM rIGF1, for 48 h. We found that IGF1, but not FSH nor GH, stimulated SC proliferation. Furthermore, an inhibitory effect of FSH, GH and IGF1 on AMH secretion, and a stimulatory role of FSH and IGF1, but not GH, on inhibin B secretion were found. These results suggest that the GH-IGF1 axis influences basal and FSH-modulated SC proliferation and function. We speculate that SC proliferation occurring in childhood might be supported by the increased serum IGF1 levels observed during this period of life.


Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses.
CTL are held to be an important host defense mechanism in persistent herpes-virus infections. We have therefore studied the nature and specificity of human cytomegalovirus (HCMV)-specific CTL in normal persistently infected individuals. This was achieved by using vaccinia recombinants encoding viral genes expressed at different stages of the virus replicative cycle, a structural glycoprotein gB (vac.gB) and the major 72-kD immediate early nonstructural protein (vac.IE) of HCMV, combined with limiting dilution analysis of the CTL response. In two subjects, 43 and 58% of HCMV CTL precursors (CTLp) lysed vac.IE-infected cells, in contrast to less than 6% lysing gB-infected cells. HCMV-specific CTL could also be generated by secondary in vitro stimulation with vac.gB- but not vac.IE-infected autologous fibroblasts. The high frequency of 72-kD IE protein-specific CTL suggests that this is at least a major recognition element for the HCMV-specific CTL response in asymptomatic persistently infected individuals, and CTL with this specificity may be important in maintaining the normal virus/host equilibrium.


Renal ischemic injury affects renal hemodynamics and excretory functions in Sprague Dawley rats: involvement of renal sympathetic tone.
The role of renal sympathetic nerves in the pathogenesis of ischemic acute renal failure (ARF) and the immediate changes in the renal excretory functions following renal ischemia were investigated. Two groups of male Sprague Dawley (SD) rats were anesthetized (pentobarbitone sodium, 60 mg kg(-1) i.p.) and subjected to unilateral renal ischemia by clamping the left renal artery for 30 min followed by reperfusion. In group 1, the renal nerves were electrically stimulated and the responses in the renal blood flow (RBF) and renal vascular resistance (RVR) were recorded, while group 2 was used to study the early changes in the renal functions following renal ischemia. In post-ischemic animals, basal RBF and the renal vasoconstrictor reperfusion to renal nerve stimulation (RNS) were significantly lower (all p < 0.05 vs. control). Mean arterial pressure (MAP), basal RVR, urine flow rate (UFR), absolute and fractional excretions of sodium (U(Na)V and FE(Na)), and potassium (U(K)V and FE(K)) were higher in ARF rats (all p < 0.05 vs. control). Post-ischemic animals showed markedly lower glomerular filtration rate (GFR) (p < 0.05 vs. control). No appreciable differences were observed in urinary sodium to potassium ratio (U(Na)/U(K)) during the early reperfusion phase of renal ischemia (p > 0.05 vs. control). The data suggest an immediate involvement of renal sympathetic nerve action in the pathogenesis of ischemic ARF primarily through altered renal hemodynamics. Diuresis, natriuresis, and kaliuresis due to impaired renal tubular functions are typical responses to renal ischemia and of comparable magnitudes.


Corneal endothelial morphology after anterior chamber lens implantation.
The morphologic features of the corneal endothelium were investigated by means of regional wide-field specular microscopy and computer-assisted morphometry in 13 eyes of nine patients who had undergone intracapsular cataract extraction with anterior chamber lens implantation more than one year previously. The endothelial cells in these patients demonstrated a significant increase in cellular elongation and the coefficient of variation in mean cell area and a significant decrease in the percentage of hexagonal endothelial cells when compared with age-matched controls (ten eyes of ten patients). The clinical implications of these long-term morphologic changes are unknown, but the changes may be indicative of an unstable endothelium or may be an early sign of continuing cell loss.


Stromal CD8+ T-cell Density—A Promising Supplement to TNM Staging in Non-Small Cell Lung Cancer.
Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates, which appears to be superior to the tumor-node-metastasis (TNM) classification in colorectal cancer. In non-small cell lung cancer (NSCLC), no immunoscore has been established, but in situ tumor immunology is recognized as highly important. We have previously evaluated the prognostic impact of several immunological markers in NSCLC, yielding the density of stromal CD8(+) tumor-infiltrating lymphocytes (TIL) as the most promising candidate. Hence, we validate the impact of stromal CD8(+) TIL density as an immunoscore in NSCLC. The prognostic impact of stromal CD8(+) TILs was evaluated in four different cohorts from Norway and Denmark consisting of 797 stage I-IIIA NSCLC patients. The Tromso cohort (n = 155) was used as training set, and the results were further validated in the cohorts from Bodo (n = 169), Oslo (n = 295), and Denmark (n = 178). Tissue microarrays and clinical routine CD8 staining were used for all cohorts. Stromal CD8(+) TIL density was an independent prognostic factor in the total material (n = 797) regardless of the endpoint: disease-free survival (P < 0.001), disease-specific survival (P < 0.001), or overall survival (P < 0.001). Subgroup analyses revealed significant prognostic impact of stromal CD8(+) TIL density within each pathologic stage (pStage). In multivariate analysis, stromal CD8(+) TIL density and pStage were independent prognostic variables. Stromal CD8(+) TIL density has independent prognostic impact in resected NSCLC, adds prognostic impact within each pStage, and is a good candidate marker for establishing a TNM-Immunoscore.


[In vitro glucose consumption in severe hyperleukocytosis. A cause of factitious hypoglycemia].
Following the observation, in a patient with leukemia, of a factitious hypoglycemia that was related to in vitro glucose consumption by leukocytes, a study of glucose fall in vitro in the blood of 17 patients with leukemia of various types and with various grades of leukocytosis was undertaken. Results show that in vitro glucose consumption is linked to the intensity of leukocytes concentration, and is independant of the type of leukocyte. Factitious hypoglycemia may thus frequently occur in patients with high blood leukocyte count. This phenomenon, that was previously described, is again of interest to day because many laboratories do not yet use any more glycolysis inhibitors that partially inhibit it. Indeed, these inhibitors interfere with measures of other biological parameters that are simultaneously determined in autoanalysers.


Isolated brain stem edema in a pediatric patient with head trauma: a case report.
Brain stem is the most vital part of our body and is a transitional region of the brain that connects the cerebrum with the spinal cord. Though, being small in size, it is full of indispensible functions such as the breathing, heart beat. Injury to the brain stem has similar effects as a brain injury, but it is more fatal. Use of the Glasgow Coma Score as a prognostic indicator of outcome in patients with head injuries is widely accepted in clinical practice. Traumatic brain stem edema in children is rare, but is associated with poor outcome. The question is that whether it is being aware of computerized tomography appearance of the posterior fossa when initial evaluating pediatric patients with head trauma at emergency clinics. Normal and edematous brain stem without an additional pathology are slightly different and not distinguished easily. On the other hand, brain stem edema should be promptly identified and appropriately treated in a short time.


[Features in human immunodeficiency virus type 1 in the neonatal period].
Different patterns of disease expression have been found in pediatric HIV1 infection. The precise timing of vertical transmission of HIV1 cannot be pinpointed. Some studies suggests that a substantial proportion of infants are infected during gestation are likely to have more extensive infection and thus more accelerated disease that infants who become infected during labor or delivery. We examined the clinical manifestations and laboratory findings in seven newborns with HIV1 infection. In all patients, have been bound clinical or laboratory features at birth. Five newborn was prematurely (71.4%). The most common clinical findings in this group was: hepatomegaly (6/7), failure to drive (6/7), esplenomegaly (5/7) and limphadenopaties (5/7). The laboratory findings was: trombopeny and cellular immunosuppression (5/7). The HIV1 infection was determined by detection of p24 antigen, chain reaction polymerase or viral cocultive in blood in the first day of live. The mortality in this group was the 70% in the first year of life. This results suggest that the timing of HIV1 infection was intrauter. This group has an accelerated disease course, developing manifestations of AIDS in first month of life and dying earlier. Although, a variety of maternal and fetal factors may contributed to the intrauter infection, for example the characteristics of the mother's infection, immune status, level of HIV1-neutralizing antibody, p24 antigaenemia prematurity and others.


Caregivers' Compliance and Perception of Daycare Centers-A Community-Based Childhood Drowning Prevention Intervention Implemented in Rural Bangladesh.
Drowning was one of the most prevalent causes of death worldwide for children under five in 2020. Drowning was the second leading cause of death for children under five in Bangladesh, while 58% of all deaths in the 1-5 years old age group resulted from drowning. Adult supervision helps prevent child drowning in rural areas where water bodies are easily accessible and located very close to homes. This paper aims to assess caregivers' compliance and perception of community daycare centers in rural Bangladesh, piloted as a child drowning prevention intervention. In this longitudinal study, each child enrolled in the daycare intervention was visited and data on compliance and satisfaction with the daycare were collected. Descriptive statistics on daycare attendance, patterns of supervision, and caregivers' perceptions about daycare were reported. When inquired about daycare attendance (n = 226,552), a total of 77.4% of children (n = 175,321) were found to attend daycare. The distance from homes and an adult's unavailability to take the child to daycare were the most common reasons for not attending or discontinuing enrollment. The majority of children (76.4%) were supervised by their mothers during daycare closures. A total of 67.7% of respondents perceived daycare to be a safe place, where children also developed cognitive (51.7%) and social skills (50.6%). There were no incidences of drowning among children while attending daycare. Rural families were found to be compliant with the daycare and professed it to be a safe place protecting children from drowning and other injuries, while allowing them to focus on household chores or income-generating activities. These findings indicate a potential for the expansion of this intervention in rural Bangladesh and similar settings.


Sex differences in cause-specific mortality: regional trends in seven European countries, 1996-2019.
Male excess mortality is mostly related to non-biological factors, and is thus of high social- and health-policy concern. Previous research has mainly focused on national patterns, while subnational disparities have been less in the focus. This study takes a spatial perspective on subnational patterns, covering seven European countries at the crossroad between Eastern and Western Europe. We analyze a newly gathered spatially detailed data resource comprising 228 regions with well-established demographic methods to assess the contribution of specific causes of death to the evolution of sex mortality differentials (SMDs) since the mid-1990s. Our results show that declines in SMDs were mostly driven by a reduction of male excess mortality from cardiovascular diseases and neoplasms (about 50-60% and 20-30%, respectively). In Western Europe, trends in deaths from neoplasms contributed more to the reduction of SMDs, while among regions located in Eastern-Central Europe narrowing SMDs were mostly driven by changes in cardiovascular disease-related deaths. Moreover, men show up to three times higher mortality levels from external causes as compared to women in several analyzed regions. But in absolute terms, external deaths play only a minor role in explaining SMDs due to their small contribution to overall mortality. We conclude that examining the regional development of SMDs is useful for introducing targeted social and health policies in order to reduce and prevent mortality inequalities between women and men.


Of rodents and men: species-specific glucose regulation and type 2 diabetes research.
Type 2 diabetes mellitus (T2DM) has reached epidemic proportions worldwide and animal models mimicking human T2DM are widely used to study mechanisms of disease and to develop pharmacotherapeutics. Over the last three decades, rodent models of T2DM have yielded more than 50 publications per month; however, many details of human T2DM pathogenesis remain unclear, and means of preventing disease progression remain elusive. This review investigates the reasons for this translational discrepancy by analyzing the experimental evidence from rodent models of T2DM. The analysis revealed significant species-specific differences at every level of glucose regulation, from gene/protein expression, cellular signaling, tissue and organ to whole organism level, when compared with data acquired using human cells, tissues, organs, and populations. Given the extensive species-specific barrier that creates an immutable translational gap, there is an urgent need to further employ and develop human-based research strategies to make significant strides against the current T2DM epidemic.


Pyrosequencing analysis of aerobic anoxygenic phototrophic bacterial community structure in the oligotrophic western Pacific Ocean.
Aerobic anoxygenic phototrophic bacteria (AAPB) represent a widespread functional bacterial group defined by their obligate aerobic and facultative photoheterotrophic abilities. They are an active part of the marine microbial community as revealed by a large number of previous investigations. Here, we made an in-depth comparison of AAPB community structures in the subsurface water and the upper twilight zone of the western Pacific Ocean using high-throughput sequencing based on the pufM gene. Approximately, 100 000 sequences, grouped into 159 OTUs (94% cut-off value), included 44 and 24 OTUs unique to the subsurface and the upper twilight zone, respectively; 92 OTUs were common to both subsurface and twilight zone, and 3 OTUs were found in all samples. Consistent with previous studies, AAPB belonging to the Gammaproteobacteria were the dominant group in the whole water column, followed by the alphaproteobacterial AAPB. Comparing the relative abundance distribution patterns of different clades, an obvious community-structure separation according to deeper or shallower environment could be observed. Sulfitobacter-like, Loktanella-like, Erythrobacter-like, Dinoroseobacter-like and Gamma-HIMB55-like AAPB preferred the high-light subsurface water, while Methylobacterium-like, 'Citromicrobium'-like, Roseovarius-like and Bradyrhizobium-like AAPB, the dim light environment.


Identification and amplification of the E. coli phr gene product.
We have constructed a series of multicopy plasmids that complement mutations in the phr gene of Escherichia coli. By subcloning into a tac plasmid vector we obtained a phr plasmid that upon induction overproduces two proteins of Mr's 49,000 and 20,000. Tn1000 insertions into the phr gene caused the disappearance of the 49,000 dalton protein, thus demonstrating this protein to be the phr gene product, DNA photolyase. The photolyase encoded by the phr gene makes up about 15% of total cellular proteins after induction of cells carrying a tac-phr plasmid. This protein binds specifically to UV (254 nm) irradiated DNA and upon exposure to near UV (300-500 nm) illumination repairs the UV damage and dissociates from DNA.


Missense mutations in β-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) cause Walker-Warburg syndrome.
Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result in defective αDG glycosylation and reduced ligand binding by αDG causing a clinically heterogeneous group of congenital muscular dystrophies, commonly referred to as dystroglycanopathies. The most severe clinical form, Walker-Warburg syndrome (WWS), is characterized by congenital muscular dystrophy and severe neurological and ophthalmological defects. Here, we report two homozygous missense mutations in the β-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) gene in a family affected with WWS. Functional studies confirmed the pathogenicity of the mutations. First, expression of wild-type but not mutant B3GNT1 in human prostate cancer (PC3) cells led to increased levels of αDG glycosylation. Second, morpholino knockdown of the zebrafish b3gnt1 orthologue caused characteristic muscular defects and reduced αDG glycosylation. These functional studies identify an important role of B3GNT1 in the synthesis of the uncharacterized laminin-binding glycan of αDG and implicate B3GNT1 as a novel causative gene for WWS.


Surgical pleth index: prediction of postoperative pain in children?
Surgical Pleth Index (SPI) is a non-invasive, dimensionless score (0-100) aimed to allow an estimate of intraoperative nociception. Thus, it may be a useful tool to guide intraoperative analgesia. However, no optimum SPI target range for the use in children has yet been defined. It was the aim of this study to define a clinically appropriate SPI target to predict moderate-severe postoperative pain in children. After ethics approval 105 children (2-16 yr) undergoing elective sevoflurane/opioid-based anaesthesia were included. SPI was recorded directly before the end of surgery and compared with acute postoperative pain (age appropriately assessed on different pain scales in the age groups two to three yr, four to eight yr and nine to16 yr) in the postoperative acute care unit (PACU). Data of 93 children were analysed. A significant negative correlation was found between age and SPI (r=-0.43; P=0.03). The SPI cut-off value with the highest sensitivity (76%) and specificity (62%) in all children combined was 40. The negative predictive value for SPI ≤ 40 to predict the absence of moderate-severe pain in PACU was 87.5%. The commonly used SPI cut-off (50) published in all related studies had neither any clinically relevant sensitivity nor specificity to predict the presence or absence of acute pain in PACU. The results suggest that a lower (≤ 40) than previously published (50) target for SPI may be more appropriate in studies investigating SPI guided anaesthesia in children, if the avoidance of moderate-severe postoperative pain is the main goal. ACTRN12616001139460.


Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures.
Endothelial cell (EC) migration, cell-cell adhesion, and the formation of branching point structures are considered hallmarks of angiogenesis; however, the underlying mechanisms of these processes are not well understood. Lipid phosphate phosphatase 3 (LPP3) is a recently described p120-catenin-associated integrin ligand localized in adherens junctions (AJs) of ECs. Here, we tested the hypothesis that LPP3 stimulates beta-catenin/lymphoid enhancer binding factor 1 (beta-catenin/LEF-1) to induce EC migration and formation of branching point structures. In subconfluent ECs, LPP3 induced expression of fibronectin via beta-catenin/LEF-1 signaling in a phosphatase and tensin homologue (PTEN)-dependent manner. In confluent ECs, depletion of p120-catenin restored LPP3-mediated beta-catenin/LEF-1 signaling. Depletion of LPP3 resulted in destabilization of beta-catenin, which in turn reduced fibronectin synthesis and deposition, which resulted in inhibition of EC migration. Accordingly, reexpression of beta-catenin but not p120-catenin in LPP3-depleted ECs restored de novo synthesis of fibronectin, which mediated EC migration and formation of branching point structures. In confluent ECs, however, a fraction of p120-catenin associated and colocalized with LPP3 at the plasma membrane, via the C-terminal cytoplasmic domain, thereby limiting the ability of LPP3 to stimulate beta-catenin/LEF-1 signaling. Thus, our study identified a key role for LPP3 in orchestrating PTEN-mediated beta-catenin/LEF-1 signaling in EC migration, cell-cell adhesion, and formation of branching point structures.


Ethical qualms while treating diabetes in low-resource areas.
Diabetes care in low-resource rural areas is often compromised by access and finance barriers, leading to ethical dilemmas for physicians in diagnosis and treatment. Rural health workers should be educated on how poverty, disproportionate rural health infrastructure, and illiteracy impact diabetes care to facilitate a paradigm shift from blaming patients for poor adherence to improving health systems in order to address underlying structural care seeking barriers of cost, distance and social stigma. With these barriers urban, high resource protocols cannot be implemented and there is need for separate evidence-based protocols for rural, low resource populations. Having such set protocols coupled with continuous training and use of mobile/telemedicine technology could help shifting tasks to nurses and peripheral health workers. The National Programme For Prevention And Control Of Cancer, Diabetes, Cardiovascular Diseases & Stroke may benefit from this communitising care model by setting up PHC-level NCD clinics run by trained nurses and health workers with physician backup using technology as needed. This way of utilizing non-physician health workers to treat uncomplicated diabetes patients may not only allow physicians quality time and more resources to treat complicated diabetes patients but also provide good quality, accessible care within everyone's reach.


The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis.
Deprescribing is a suggested intervention to reverse the potential iatrogenic harms of inappropriate polypharmacy. The review aimed to determine whether or not deprescribing is a safe, effective and feasible intervention to modify mortality and health outcomes in older adults. Specified databases were searched from inception to February 2015. Two researchers independently screened all retrieved articles for inclusion, assessed study quality and extracted data. Data were pooled using RevMan v5.3. Eligible studies included those where older adults had at least one medication deprescribed. The primary outcome was mortality. Secondary outcomes were adverse drug withdrawal events, psychological and physical health outcomes, quality of life, and medication usage (e.g. successful deprescribing, number of medications prescribed, potentially inappropriate medication use). A total of 132 papers met the inclusion criteria, which included 34 143 participants aged 73.8 ± 5.4 years. In nonrandomized studies, deprescribing polypharmacy was shown to significantly decrease mortality (OR 0.32, 95% CI: 0.17-0.60). However, this was not statistically significant in the randomized studies (OR 0.82, 95% CI 0.61-1.11). Subgroup analysis revealed patient-specific interventions to deprescribe demonstrated a significant reduction in mortality (OR 0.62, 95% CI 0.43-0.88). However, generalized educational programmes did not change mortality (OR 1.21, 95% CI 0.86-1.69). Although nonrandomized data suggested that deprescribing reduces mortality, deprescribing was not shown to alter mortality in randomized studies. Mortality was significantly reduced when applying patient-specific interventions to deprescribe in randomized studies.


Nanostructured electrochromic smart windows: traditional materials and NIR-selective plasmonic nanocrystals.
Electrochromic devices, which dynamically change colour under applied potential, are widely studied for use in energy-efficient smart windows. To improve the viability of smart windows, many researchers are utilizing nanomaterials, which can provide electrochromic devices with improved colouration efficiencies, faster switching times, longer cycle lives, and potentially reduced costs. In an effort to demonstrate a new type of electrochromic device that goes beyond the capabilities of commonly used electrochromic materials, researchers have turned to plasmonic transparent conductive oxide (TCO) nanocrystals. Electrochemical injection of electrons into plasmonic TCO nanocrystal films induces a shift in the plasmon frequency and gives rise to the new functionality of selective optical modulation in the near-infrared region of the solar spectrum. These nanocrystals can be used as building blocks to enable creation of advanced electrochromic devices containing mesoporous electrodes or nanocrystal-in-glass composites. Such devices have been important in advancing the field towards achieving the ideal smart window with independent control over visible and NIR transmittance.


Protective impacts of household-based tuberculosis contact tracing are robust across endemic incidence levels and community contact patterns.
There is an emerging consensus that achieving global tuberculosis control targets will require more proactive case finding approaches than are currently used in high-incidence settings. Household contact tracing (HHCT), for which households of newly diagnosed cases are actively screened for additional infected individuals is a potentially efficient approach to finding new cases of tuberculosis, however randomized trials assessing the population-level effects of such interventions in settings with sustained community transmission have shown mixed results. One potential explanation for this is that household transmission is responsible for a variable proportion of population-level tuberculosis burden between settings. For example, transmission is more likely to occur in households in settings with a lower tuberculosis burden and where individuals mix preferentially in local areas, compared with settings with higher disease burden and more dispersed mixing. To better understand the relationship between endemic incidence levels, social mixing, and the impact of HHCT, we developed a spatially explicit model of coupled household and community transmission. We found that the impact of HHCT was robust across settings of varied incidence and community contact patterns. In contrast, we found that the effects of community contact tracing interventions were sensitive to community contact patterns. Our results suggest that the protective benefits of HHCT are robust and the benefits of this intervention are likely to be maintained across epidemiological settings.


Part-task training in the context of automation: current and future directions.
Automation often elicits a divide-and-conquer outlook. By definition, automation has been suggested to assume control over a part or whole task that was previously performed by a human (Parasuraman & Riley, 1997). When such notions of automation are taken as grounds for training, they readily invoke a part-task training (PTT) approach. This article outlines broad functions of automation as a source of PTT and reviews the PTT literature, focusing on the potential benefits and costs related to using automation as a mechanism for PTT. The article reviews some past work in this area and suggests a path to move beyond the type of work captured by the "automation as PTT" framework. An illustrative experiment shows how automation in training and PTT are actually separable issues. PTT with automation has some utility but ultimately remains an unsatisfactory framework for the future broad potential of automation during training, and we suggest that a new conceptualization is needed.


Socioeconomic Predictors of Surgical Resection and Survival for Patients With Osseous Spinal Neoplasms.
Primary osseous spinal neoplasms (POSNs) include locally aggressive tumors such as osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. For such tumors, surgical resection is associated with improved survival for patients. Socioeconomic predictors of receiving surgery, however, have not been studied. To examine the independent effect of race on receiving surgery and survival probability in patients with POSN. A total of 1904 patients from the SEER program at the National Cancer Institute database, all diagnosed with POSN of the spinal cord, vertebral column, pelvis, or sacrum from 2003 through 2012 were included in the study. Race was reported as white or nonwhite. Treatment included receiving surgery and no surgery. Multivariable logistic regression was used to determine odds of receiving surgery based on race. Survival probability based on and race and surgery status was analyzed by Cox proportional hazards model and Kaplan-Meir curves. Results were adjusted for age at diagnosis, sex, socioeconomic status (composite index), tumor size, and tumor grade. Data were analyzed with SAS version 9.4. The study found that white patients were significantly more likely to receive surgery (odds ratio=3.076, P<0.01). Furthermore, nonwhite race was associated with significantly shorter survival time [hazard ratio (HR)=1.744, P<0.05]. Receiving surgery was associated with improved overall survival (HR=2.486, P<0.01). After adjusting for receiving surgery, white race remained significantly associated with higher survival probability (HR=2.061, P<0.05). This national study of patients with typically aggressive POSN found a significant correlation between race and the likelihood of receiving surgery. The study also found race to be a significant predictor of overall survival, regardless of receiving surgical treatment. These findings suggest an effect of race on receiving treatment and survival in patients with POSN, regardless of socioeconomic status. Further studies are required to understand reasons underlying these findings, and how they may be addressed.


Impulse oscillometry in adults with bronchiectasis.
The usefulness of impulse oscillometry (IOS) in bronchiectasis has not been systematically investigated. To determine the usefulness of IOS parameters and their correlation with radiology, disease severity, sputum bacteriology, and spirometry, and to compare the changes in IOS parameters during exacerbations and convalescence of bronchiectasis. We recruited 100 patients with bronchiectasis and 28 healthy subjects. Receiver operating characteristic curve was plotted to analyze the diagnostic performance of IOS parameters. Chest high-resolution computed tomography (HRCT), Bronchiectasis Severity Index (BSI) assessment, sputum culture, and spirometry were performed. Correlation between IOS parameters and clinical indices was determined using the Spearman model. Changes in IOS parameters, compared with spirometry, during exacerbation were assessed in 16 patients with bronchiectasis. IOS parameters (in particular, resonant frequency) could discriminate patients with bronchiectasis from healthy subjects. Higher levels of IOS parameters were associated with Pseudomonas aeruginosa infection, dyshomogeneity, higher BSI and HRCT score, more bronchiectatic lobes, and cystic bronchiectasis (all P < 0.05). All IOS parameters but lung resistance at 5 Hz were positively correlated with the duration of bronchiectasis symptoms, number of bronchiectatic lobes, HRCT total scores, and BSI (all P < 0.05), but not sputum bacterial density (P > 0.05). IOS parameters, but not spirometric parameters, were not statistically different between peripheral and peripheral plus central segment bronchiectasis (all P > 0.05). Increased frequency dependence (higher resonance frequency or reactance area) was more likely to be associated with lower HRCT scores (≤5) than FEV1. Compared with FEV1, any single IOS parameter being abnormal was more common in mild bronchiectasis, particularly in patients with HRCT score of 5 or lower. IOS parameters were not statistically different from baseline to exacerbations and convalescence (all P > 0.05). IOS parameters correlate with clinical indices and could reflect peripheral airway abnormality. An increased number of aberrant IOS parameters signals poorer clinical conditions. Increased frequency dependence might be a sensitive marker of mild bronchiectasis. Any single IOS parameter being abnormal sensitively reflects mild bronchiectasis. IOS parameters do not change significantly during bronchiectasis exacerbations. Clinical Trial registered with www.clinicaltrials.gov (NCT01761214).


Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer.
Abiraterone acetate (abiraterone) prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). This study's objective was to retrospectively identify factors associated with prostate-specific antigen (PSA) response to abiraterone and validate them in an independent cohort. We hypothesized that the neutrophil/lymphocyte ratio (NLR), thought to be an indirect manifestation of tumor-promoting inflammation, may be associated with response to abiraterone. All patients receiving abiraterone at the Princess Margaret (PM) Cancer Centre up to March 2013 were reviewed. The primary end point was confirmed PSA response defined as PSA decline ≥50% below baseline maintained for ≥3 weeks. Potential factors associated with PSA response were analyzed using univariate and multivariable analyses to generate a score, which was then evaluated in an independent cohort from Royal Marsden (RM) NHS foundation. A confirmed PSA response was observed in 44 out of 108 assessable patients (41%, 95% confidence interval 31%-50%). In univariate analysis, lower pre-abiraterone baseline levels of lactate dehydrogenase, an NLR ≤ 5 and restricted metastatic spread to either bone or lymph nodes were each associated with PSA response. In multivariable analysis, only low NLR and restricted metastatic spread remained statistically significant. A score derived as the sum of these two categorical variables was associated with response to abiraterone (P = 0.007). Logistic regression analysis on an independent validation cohort of 245 patients verified that this score was associated with response to abiraterone (P = 0.003). It was also associated with OS in an exploratory analysis. A composite score of baseline NLR and extent of metastatic spread is associated with PSA response to abiraterone and OS. Our data may help understand the role of systemic inflammation in mCRPC and warrant further research.


Towards a robust description of intrinsic protein disorder using nuclear magnetic resonance spectroscopy.
In order to understand the conformational behaviour of Intrinsically Disordered Proteins (IDPs), it is essential to develop a molecular representation of the partially folded state. Due to the very large number of degrees of conformational freedom available to such a disordered system, this problem is highly underdetermined. Characterisation therefore requires extensive experimental data, and novel analytical tools are required to exploit the specific conformational sensitivity of different experimental parameters. In this review we concentrate on the use of nuclear magnetic resonance (NMR) spectroscopy for the study of conformational behaviour of IDPs at atomic resolution. Each experimental NMR parameter is sensitive to different aspects of the structural and dynamic behaviour of the disordered state and requires specific consideration of the relevant averaging properties of the physical interaction. In this review we present recent advances in the description of disordered proteins and the selection of representative ensembles on the basis of experimental data using statistical coil sampling from flexible-meccano and ensemble selection using ASTEROIDS. Using these tools we aim to develop a unified molecular representation of the disordered state, combining complementary data sets to extract a meaningful description of the conformational behaviour of the protein.


Discussion about the use of the volume specific surface area (VSSA) as a criterion to identify nanomaterials according to the EU definition. Part two: experimental approach.
The first part of this study was dedicated to the modelling of the influence of particle shape, porosity and particle size distribution on the volume specific surface area (VSSA) values in order to check the applicability of this concept to the identification of nanomaterials according to the European Commission Recommendation. In this second part, experimental VSSA values are obtained for various samples from nitrogen adsorption isotherms and these values were used as a screening tool to identify and classify nanomaterials. These identification results are compared to the identification based on the 50% of particles with a size below 100 nm criterion applied to the experimental particle size distributions obtained by analysis of electron microscopy images on the same materials. It is concluded that the experimental VSSA values are able to identify nanomaterials, without false negative identification, if they have a mono-modal particle size, if the adsorption data cover the relative pressure range from 0.001 to 0.65 and if a simple, qualitative image of the particles by transmission or scanning electron microscopy is available to define their shape. The experimental conditions to obtain reliable adsorption data as well as the way to analyze the adsorption isotherms are described and discussed in some detail in order to help the reader in using the experimental VSSA criterion. To obtain the experimental VSSA values, the BET surface area can be used for non-porous particles, but for porous, nanostructured or coated nanoparticles, only the external surface of the particles, obtained by a modified t-plot approach, should be considered to determine the experimental VSSA and to avoid false positive identification of nanomaterials, only the external surface area being related to the particle size. Finally, the availability of experimental VSSA values together with particle size distributions obtained by electron microscopy gave the opportunity to check the representativeness of the two models described in the first part of this study. They were also used to calculate the VSSA values and these calculated values were compared to the experimental results. For narrow particle size distributions, both models give similar VSSA values quite comparable to the experimental ones. But when the particle size distribution broadens or is of multi-bimodal shape, as theoretically predicted, one model leads to VSSA values higher than the experimental ones while the other most often leads to VSSA values lower than the experimental ones. The experimental VSSA approach then appears as a reliable, simple screening tool to identify nano and non-nano-materials. The modelling approach cannot be used as a formal identification tool but could be useful to screen for potential effects of shape, polydispersity and size, for example to compare various possible nanoforms.


Exercise-induced Anaphylaxis: the Role of Cofactors.
Anaphylaxis is a dramatic clinical emergency. It is a very severe, life-threatening generalized or systemic hypersensitivity reaction. Based on immunologic mechanism the anaphylaxis is divided in IgE, IgG, complement, or immune complexes-mediated vs non allergic anaphylaxis. There are a lot of etiologic factors of anaphylaxis, but the three principal immunologic triggers are drugs, insect stings, and foods. Regarding the clinical severity there are several proposed grading systems. The diagnosis of anaphylaxis is mainly clinical. The anaphylaxis markers measured in clinical laboratories are total tryptase and histamine. There are some conditions that modulate the onset of anaphylaxis, acting as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. The well-documented cofactors of anaphylaxis are physical exercise, alcohol consumption, some foods, co-administration of nonsteroidal anti-inflammatory drugs (NSAID), and concomitant infectious diseases. Development of anaphylaxis depends on the sensitization pattern, the proportion of the involved immunoglobulin classes, characteristics of the allergen, the proportion of the involved immunoglobulin classes, the avidity and affinity of immunoglobulins to bind an allergen, the route of allergen application, and, last but not least, the presence of cofactors of anaphylaxis. Anaphylaxis remains a continuous challenge for the diagnosis and treatment. The adequate management of anaphylaxis requires rapid diagnosis, implementation of primary and secondary prevention measures, and immediate administration of subcutaneous epinephrine.


The orphan nuclear receptors NURR1 and NGFI-B modulate aromatase gene expression in ovarian granulosa cells: a possible mechanism for repression of aromatase expression upon luteinizing hormone surge.
Ovarian granulosa cells play pivotal roles in many aspects of ovary functions including folliculogenesis and steroidogenesis. In response to FSH and LH, the elevation of intracellular cAMP level in granulosa cells leads to activation of multiple ovarian genes. Here, we report findings from a genome-wide study of the cAMP-responsive gene expression profiles in a human granulosa-like tumor cell line, KGN. The study identified 140 genes that are either activated or repressed by 2-fold or greater after stimulation by the adenylyl cyclase activator forskolin. The induction patterns of some cAMP-responsive genes were further analyzed by quantitative real-time PCR. Consistent with previous observations, the LH-responsive genes, such as the nuclear receptor 4A subfamily (NURR1, NGFI-B, and NOR-1), were rapidly but transiently induced, whereas the FSH-responsive gene CYP19 encoding aromatase was induced in a delayed fashion. Interestingly, ectopic expression of NURR1 or NGFI-B severely attenuated the cAMP-responsive activation of the ovary-specific aromatase promoter. Reduction of the endogenous NURR1 or NGFI-B by small interfering RNA significantly elevated aromatase gene expression. The cis-elements responsible for NURR1/NGFI-B-mediated repression were mapped to the minimal aromatase promoter sequence that confers camp responsiveness. Furthermore, the DNA-binding domain of NURR1 was required for the repression. Taken together, these results strongly suggest a causal relationship between the rapid decline of aromatase mRNA and induction of nuclear receptor subfamily 4A expression, which concomitantly occur upon LH surge at the later stages of ovarian follicular development.


"Building the Threads of Connection that We Already Have": The Nature of Connections via Technology for Older People.
Objectives: The social connectedness of older people is of increasing concern. Technology has been suggested for enhancing social inclusion. This study aimed to explore the nature and quality of connections via technology.Methods: Qualitative exploration of experiences, stories, and needs was undertaken through semi-structured interviews with older (7) and middle-aged (3) adults with rich experience of connections via technology in Australia and England. Core aspects of connections through technology were constructed through interpretive description analysis.Results: Four key aspects were: 1. The caliber of connections: descriptions of a range of subjective quality of connections and characteristics of good connections; 2. Experiences of poor connection (mis- and dis-connection) including descriptions of experiences creating isolation; 3. Reasons to connect described the purposes of technology-based connections including connecting with others, themselves and places important to them; 4. Making connections work described active strategies to enhance connection.Conclusions: Using technology is part of the social engagement of many people. Considering the related feelings of connection and support strategies and needs could enhance future research and practice with older people.Clinical implications: The different characteristics and potential positive and negative experiences of connection via technology need consideration in measuring social isolation and supporting older adults.


Self-reported preferences and barriers to continued professional development in primary care physicians: a cross-sectional web-based survey in Qatar.
High quality and effective primary healthcare is a national priority in Qatar. Continuing professional development (CPD) for physicians is a cornerstone of this objective, yet little is known about physicians' preferences or barriers to CPD participation. A needs assessment was conducted using a cross-sectional web-based survey of primary care physicians registered with the Department of Healthcare Practitioners (DHP) between March and June 2017. Two-hundred-and-eighty-one complete surveys were submitted representing physicians in both public (N = 129) and private sectors (N = 152). Physicians completed medical degrees and postgraduate training across multiple countries, and most had been practicing in Qatar for 5 years or less. 'Activities during working hours', 'cost' and 'work commitments' were the most common barriers. There was little consensus regarding the optimal timing of CPD activities, although public sector physicians were more likely to indicate weekend activities as a barrier to participation (30% vs. 9%). Over 90% of participants preferred traditional lectures, workshops, case-based sessions, small group and online self-paced learning as formats for CPD delivery, however alternative modes of delivery were also deemed acceptable (> 80% agreement). Understanding primary care physicians' barriers and preferences is an essential component of a larger necessitated needs assessment of CPD in primary care practitioners in Qatar. Further research is warranted to understand the underlying beliefs driving physicians' choices and the apparent variation between those working in the public and private sectors. CPD developers should consider approaches to mitigate perceived barriers and understand preferences to maximize the quality of participation.


Differences in non-suicidal self-injury and suicide attempts in adolescents.
As suicide attempts and self-injury remain predominant health risks among adolescents, it is increasingly important to be able to distinguish features of self-harming adolescents from those who are at risk for suicidal behaviors. The current study examined differences between groups of adolescents with varying levels of self-harmful behavior in a sample of 373 high school students with a mean age of 15.04 (SD = 1.05). The sample was 48% female and the distribution of ethnicity was as follows: 35% Caucasian, 37.2% African-American, 16% Multi-ethnic, 9.2% Hispanic, and 2.3% Asian. The sample was divided into three groups: no history of self-harm, non-suicidal self-injury (NSSI) only, and NSSI in addition to a suicide attempt. Differences in depressive symptoms, suicidal ideation, social support, self-esteem, body satisfaction, and disordered eating were explored. Results indicated significant differences between the three groups on all variables, with the no self-harm group reporting the lowest levels of risk factors and highest levels of protective factors. Further analyses were conducted to examine specific differences between the two self-harm groups. Adolescents in the NSSI group were found to have fewer depressive symptoms, lower suicidal ideation, and greater self-esteem and parental support than the group that also had attempted suicide. The clinical implications of assessing these specific psychosocial correlates for at-risk adolescents are discussed.